terms,relevant
understanding psychological effects multiple sclerosis ,0.0
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singulto persistente en dos pacientes con infeccin por sarscov2 reporte de casos y revisin de la literatura ,0.0
implication genetic variants primary microrna processing sites risk multiple sclerosis ,0.0
efficiency safety umbilical cord mesenchymal stromal#x2f stem cells multiple sclerosis combined treatment ,0.0
breakthrough sarscov2 infections covid19 mrna vaccination ms patients disease modifying therapies delta omicron waves italy ,0.0
shiatsuassociated physical therapy pain fatigue people multiple sclerosis abstract introduction pain fatigue common symptoms multiple sclerosis ms shiatsu technique uses pressure fingers associated manual therapy exercises stretching can used control symptoms objective evaluate effect shiatsu associated physical therapy pain fatigue people ms methods randomized clinical trial people diagnosed ms divided two groups intervention group ig shiatsuassociated physical therapy n 9 control group cg n 8 participants assessed treatment expanded disability status scale edss neuropathic pain questionnaire dn4 visual analog scale vas fatigue impact scale mfis description sociodemographic results seventeen people ms 9 men aged 4518 306 years participated study total sample average dn4 165 2002 vas 229 280 mfis 3947 2967 529 score 38 mfis corresponds presence fatigue values pre postintervention grade p respectively ig dn4 278 216 20 212 0432 eva 322 327 033 100 0023 total mfis 4444 3591 35 3170 0068 cg values dn4 038 0744 225 271 0054 eva 125 183 363 238 0043 mfis 3388 2168 2513 2422 0379 conclusion shiatsu associated physiotherapy effective improving pain fatigue individuals ms,0.0
comparison switching 6week dosing natalizumab versus continuing 4week dosing patients relapsingremitting multiple sclerosis nova randomised controlled openlabel phase 3b trial ,0.0
natalizumab multiple sclerosis dilemma nova ,0.0
canonical noncanonical regulatory roles jak2 pathogenesis rheumatoid arthritisassociated interstitial lung disease idiopathic pulmonary fibrosis abstractidiopathic pulmonary fibrosis ipf rheumatoid arthritisassociated interstitial lung disease raild two fibrotic interstitial lung diseases share usual interstitial pneumonia uip injury pattern report rna sequencing lung biopsies patients raild ipf revealed shared distinct diseasecausing pathways analysis transcriptomic data identified jak2 related jak stat signaling pathway gene signature distinguishes rauip idiopathic uip confirmed immunohistostaining identified jak2 phosphorylation two distinct forms activation cytoplasmic form jak2 activation ipf cases 13 20 nuclear form pjak2 rauip 5 5 minority ipf 6 20 cases immunohistostaining identified stat5ab downstream transcriptional activator jak2mediated canonical signal transduction phosphorylation tyr41 histone h3 h3y41ph downstream epigenetic regulation site jak2mediated noncanonical signal transduction gene set enrichment analysis gsea rnaseq data supported shared pathogenic mechanism two diseases enrichment stat5ab target gene sets well jak2 regulated h3y41ph target gene set regulatory role jak2 pathogenesis pulmonary fibrosis demonstrated attenuation bleomycininduced murine pulmonary fibrosis using jak2selective pharmacological inhibitor cep33779 vitro studies normal ipf derived lung fibroblasts revealed central role jak2 essential intermediary molecule tgfmediated myofibroblast transdifferentiation proliferation extracellular matrix protein production observations support crucial role jak2 intermediary molecule fibrotic lung disease development,0.0
cell based treatment autoimmune diseases children mesenchymal stem cells recently recoined medicinal signaling cells msc ability promote tissue homeostasis immune modulation angiogenesis tropism last 20 years plethora publications using msc adults lesser extent neonates variety illnesses parts world autologous allogeneic mscs purified used treat range autoimmune conditions including graft versus host disease,0.0
hla amyotrophic lateral sclerosis systematic review metaanalysis background amyotrophic lateral sclerosis als neurodegenerative disease associated loss upper lower motor neurones leads death respiratory failure typical prognosis 23 years immune system shown play role pathophysiology als important immune genes within human leukocyte antigen hla region recent genomewide association study gwas identified risk allele als within hla region,0.0
accumulation ptreg cells detrimental lateonset aged mouse model multiple sclerosis although typically associated onset young adults multiple sclerosis ms also attacks elderly termed lateonset ms disease can recapitulated studied mouse model experimental autoimmune encephalomyelitis eae onset induced eae delayed aged mice disease severity increased relative young eae mice given cd4 + foxp3 + regulatory t treg cells play ameliorative role ms eae severity aged immune system,0.0
molecular mechanisms genesis seizures epilepsy associated viral infection seizures common presenting symptom viral infections central nervous system cns can occur initial phase infection early acute symptomatic seizures recovery late spontaneous seizures indicating development acquired epilepsy development acute delayed seizures may shared well unique pathogenic mechanisms prognostic implications based extensive review literature present,0.0
clinical characteristics outcomes multiple sclerosis neuromyelitis optica spectrum disorder brainstem lesions heralding prodrome conclusion patients ms nmosd differentiating clinical manifestations time first brainstem lesions include central hiccups vomiting pyramidal tract signs abnormal eye movements additionally distinct imaging manifestations lesion location s morphology may also aid development pathognomonic criteria leading timely initial diagnosis ms nmosd,0.0
relationship csf neurofilament levels mri lesion location disease activity multiple sclerosis conclusions baseline csf nfl correlate current future mri activity lesion location however baseline mri activity explained around 53 variation follow csf nfl suggesting relationship mri csf nfl mainly precedent rather association one occurring another,0.0
treatment experimental autoimmune encephalomyelitis using aav gene therapy blocking tcell costimulatory pathways multiple sclerosis ms chronic autoimmune disease central nervous system cns characterized inflammation demyelination presently repeated relapses ms necessitate longterm immuneregulatory therapy blocking cd28b7 cd40cd40l costimulatory pathways effective synergistic method prevention amelioration clinical symptoms experimental autoimmune encephalomyelitis eae mouse model ms study explore efficacy,1.0
safety adherence persistence realworld cohort german ms patients newly treated ocrelizumab first insights confidence study conclusions ocrelizumab safety profile observed confidence realworld ms population consistent one observed pivotal clinical trials high treatment persistence adherence observed,0.0
instrumented assessment motor performance fatigability 6min walk test mildly affected people multiple sclerosis conflicting results regarding changes spatiotemporal gait parameters 6min walk test 6mwt indicators gaitrelated motor performance fatigability pf people multiple sclerosis pwms analyze gaitrelated motor pf can quantified using instrumented gait analysis 6mwt investigated whether gait parameters recorded first second minute stable thus better baseline assess motor pf,0.0
beyond myelination possible roles immune proteasome oligodendroglial homeostasis dysfunction oligodendroglia play critical role cns homeostasis myelinating neuronal axons mature stages dysfunction lineage occurs early stage opcs able differentiate replace dying mature myelinating oligodendrocytes many hypotheses exist de hypomyelinating disorders diseases occur review present data show oligodendroglia can adopt components immune proteasome inflammatory conditions works reviewed,1.0
association pain plasma c5a patients neuromyelitis optica spectrum disorders remission conclusion nmosd patients remission elevated c5a related inflammatory cytokines levels peripheral blood elevated c5a may unique role pathogenesis pain nmosd patients,0.0
impact telehealth health care multiple sclerosis outpatient clinic covid19 pandemic abstractbackgroundthe coronavirus disease 2019 covid19 pandemic precipitated expansion telemedicine outpatient management chronic diseases including multiple sclerosis ms studies conducted prepandemic telehealth alternative inperson consultations represent different setting current practice aim study assess impact telehealth ms outpatient care tertiary metropolitan hospital melbourne australia covid19 pandemicmethodfrom marchdecember 2020 patients clinicians ms outpatient clinic surveyed regarding attitudes towards telehealth scores expanded disability status scale edss telehealth facetoface appointments study period compared scores facetoface consultations period medical records reviewed compare management decisions made telehealth versus facetoface consultations diagnoses treatment ms relapses compared 2019resultstelehealth used 73 outpatient appointments patient satisfaction generally high patients clinicians preferred facetoface consultations willing use telehealth longer term overall significant delays identifying patients experiencing disability worsening via telehealth edss increase recorded facetoface telehealth appointments particularly lower baseline disability diseasemodifying therapy commencement rates similar symptomatic therapy initiation investigation requests occurred frequently facetoface visits comparable numbers ms relapses diagnosed treated corticosteroids 2019 2020conclusionspatient satisfaction telehealth high clinicians patients preferred inperson appointments telehealth implementation lead high rates undetected disability worsening undiagnosed acute relapses telehealthbased edss assessment may underestimate lower scores treatment inertia may affect management decisions telehealth consultations telehealth will likely play role outpatient settings beyond covid19 pandemic studies longterm impact clinical outcomes required,0.0
role macrophages development neuroinflammation multiple sclerosis multiple sclerosis ms chronic demyelinating neurodegenerative disease central nervous system autoimmune mechanism development known along t blymphocytes cells innate immune system also play significant role pathogenesis ms macrophages central functioning innate immune response depending phenotype proand antiinflammatory properties central nervous system resident macrophages,1.0
vivo accelerated developmental myelination model testing promyelinating therapeutics conclusions t4treated rat pups increased mbp expression levels higher mri fractional anisotropy values indications accelerated myelination simple developmental myelination model affords rapid test promyelinating activity vivo within several days facilitate vivo prescreening candidate therapeutic compounds developmental hypomyelinating diseases research will necessary assess utility platform screening,1.0
opportunities multiomics approach search new diagnostic therapeutic targets multiple sclerosis multiple sclerosis extremely heterogeneous disease despite intensive research selective biomarkers identified pathology therefore diagnosis early stages still challenging one powerful tools studying pathogenesis multiple sclerosis multiomics approach makes possible characterize cells involved disease progression detailed versatile way review will describe current,0.0
role basket trials drug development neurodegenerative disorders conclusions basket trials may increase drug development efficiency reducing redundancy trial implementation enhancing recruitment sharing placebo groups using biomarkers relevant mechanism action treatment across ndds relatively basket trials including multiple ndds trial conducted past 10 years use basket trial strategy may represent opportunity increase efficiency development programs agents,0.0
vitamin d deficiency primary sjgrens syndrome association clinical manifestations immune activation markers vitamin d agent involved bone mineral homeostasis recognized potent immunomodulator immuneenhancing properties induces immune tolerance vitamin d deficiency shown related development autoimmune disorders vitamin d deficiency observed patients rheumatoid arthritis ra shown related disease activity vitamin d deficiency also found patients systemic lupus,0.0
longterm cardiac safety ozanimod phase 3 clinical program ulcerative colitis relapsing multiple sclerosis abstract,0.0
immunomodulatory properties vitamin d since discovery vitamin d shown immunostimulatory immunomodulatory effects immune system growing body evidence far linked vitamin d deficiency development severity several systemic organ specific autoimmune inflammatory diseases systemic lupus erythematosus rheumatoid arthritis inflammatory bowel disease multiple sclerosis present report multiple diverse effects vitamin d immune system,0.0
antisense modulation il7r splicing control sil7r expression human cd4 t cells interleukin 7 receptor il7r strongly associated increased risk develop multiple sclerosis ms autoimmune disease central nervous system association likely driven upregulation soluble isoform il7r sil7r expression sil7r determined exclusion alternative exon 6 il7r transcripts previous work revealed ms risk allele snp rs6897932 within exon enhances expression sil7r promoting,0.0
myelin water imaging using shorttr adiabatic inversionrecovery stair sequence conclusions stair sequence provides selective mwi brain can quantify reductions mw content patients multiple sclerosis,1.0
experiences using patient public involvement digital health research multiple sclerosis patient public involvement ppi increasingly used improving quality research many barriers translating ppi practice including lacking examples good practices frameworks developed one setting readily transfer settings paper examine implementation ppi context digital health research project explores design development use mhealth persons multiple sclerosis taking,0.0
effect endurance training cardiopulmonary fitness people multiple sclerosis abstractintroductiondisturbances associated multiple sclerosis ms can due pathologic process disease insufficient physical fitness benefits exercise improving cardiopulmonary fitness demonstrated animal studies also clinical trials cardiovascular patients healthy human cases however effectiveness people ms pwms still unknown people ms often engage rehabilitation programs exercise tolerance improvement therefore necessary investigate effect specific intervention cardiopulmonary fitness patients present study intended illustrate etiology exercise intolerance pwms also effects exercise etiological factorsmethods resultsthe present interventional study included 21 female patients suffering relapsingremitting ms rrms mean age 35518 years expanded disability status scale edss scores 1 4 participants underwent cardiopulmonary exercise testing cpet ergometer pre postintervention intervention included 18 sessions endurance training using stationary bicycle intensity 70 peak heart rate hr 60 peak vo2 volume oxygen consumption supervision cardiac monitoring total 24 variables including parameters cardiopulmonary fitness aerobic fitness investigated also maximal variables analyzed rer respiratory exchange ration mean rer 092 pre postintervention according results total 17 variables 24 study variables significant changes p005 conclusionthe present study showed even short 6week course aerobic exercise change peak hr vo2 improving cardio pulmonary fitness patients indicates adaptation cardiopulmonary system exercise pwms words cardiopulmonary fitness variables improvement due exercise demonstrates pathology merely caused msinduced central nervous system cns involvement can improved improving cardiopulmonary fitness,0.0
early use highefficacy diseasemodifying therapies makes difference people multiple sclerosis expert opinion multiple sclerosis ms chronic progressive neurological disease characterized neuroinflammation demyelination neurodegeneration occurring earliest phases disease may underestimated ms patients accumulate disability relapseassociated worsening progression independent relapse activity early intervention highefficacy diseasemodifying therapies hedmts may represent best window opportunity delay irreversible,1.0
resilience moderator relationship disability related stress community participation individuals multiple sclerosis resilience can defined ones ability maintain return relatively stable psychological physical functioning despite stressful life events adversity people multiple sclerosis ms building resilience shown contribute enhanced positive rehabilitation mental health outcomes however literature examining role resilience influencing relationship disabilityrelated stress community participation individuals,0.0
epsteinbarr virus key player development multiple sclerosis abstract,0.0
acute presentation newly diagnosed multiple sclerosis associated polymerase chain reactionproven human herpesvirus 6 central nervous system infection present case 26yearold male found human herpesvirus 6 hhv6 cerebrospinal fluid csf acute presentation multiple sclerosis ms paresthesia lower extremities symptom initial presentation workup ms included evaluation single dose iv steroids failed improve condition symptoms became severe upon secondary evaluation mri revealed whitematter disease plaques,0.0
experiences individuals multiple sclerosis stroke using transcutaneous foot drop electrical stimulators systematic review metasynthesis qualitative studies conclusions recommend outcomes continued use foot drop electrical stimulators carefully considered barriers conceptual model may useful guide clinical conversations around possible use fes managing foot drop people multiple sclerosis strokeimplications rehabilitationthe key outcomes foot drop electrical stimulator use enhanced walking ability improved independence confidence enhanced social,0.0
risk serious infections multiple sclerosis patients disease course disability status results swedish registerbased study conclusions disease course edss score may readily available ms course patients considered individual management monitoring ms patients including assessing benefitrisk therapies influence general immune function,0.0
targeted literature search phenomenological review perspectives people multiple sclerosis healthcare professionals immunology diseasemodifying therapies conclusions targeted literature search phenomenological review confirms pwms preferences empowered decisionmaking disease management treatment selection optimize independence safety efficacy also identifies unmet need improved communication information tools convey ms information relatable manner furthermore review seeks address unmet need providing plain language figures descriptions ms immune mechanisms can,0.0
correction current standing autologous haematopoietic stem cell transplantation treatment multiple sclerosis abstract,0.0
multiple sclerosis autoimmunity veiled relationship multiple sclerosis ms autoimmune inflammatory illness affects central nervous system cns bodys immune system attacks tissue characterized demyelination varying degrees axonal loss article compiled various studies elaborating ms autoimmune diseases ads cooccurrence several conditions fall category including type 1 diabetes t1d rheumatoid arthritis ra guillainbarre syndrome gbs myasthenia gravis,1.0
mental fatigue substantially alter neuromuscular function young healthy males females neuromuscular mechanisms leading impaired motor performance mental fatigue mf wellunderstood little known sexspecific differences neuromuscular response mf purpose study investigate sexrelated differences impact mf neuromuscular function thirty young healthy adults 15f 15m performed psychomotor vigilance task pvt induce mf watched earth documentary control 30 minutes random,0.0
high levels blood circulating immune checkpoint molecules children newonset type 1 diabetes associated risk developing additional autoimmune disease conclusions interpretation findings suggest soluble cd137 41bb pd1 molecules may used prognostic biomarkers children type 1 diabetes may pave way novel immunological screening diabetes onset allowing early identification children higher risk developing autoimmune conditions time,0.0
network alterations underlying anxiety symptoms early multiple sclerosis conclusion anxietyrelated prefrontal cortical atrophy ms leads specific network alteration involving structures resemble known neurobiological anxiety circuits findings elucidate emergence anxiety part disease pathology might ultimately enable targeted treatment approaches modulating brain networks ms,0.0
narrative review axonal neuroprotection multiple sclerosis multiple sclerosis ms chronic inflammatory disease central nervous system cns resulting demyelination neurodegeneration therapeutic strategy now largely based reducing inflammation immunosuppressive drugs unfortunately disease progression observed drug offers neuroprotection apart antiinflammatory effect review explore current knowledge assessment neurodegeneration ms look putative targets might,1.0
annual urodynamic follow multiple sclerosis yes abstract,0.0
multiparametric score assessing individual risk severe covid19 among patients multiple sclerosis abstractbackgroundmany risk factors development severe forms covid19 identified applying general population others specific multiple sclerosis ms patients however score quantifying individual risk severe covid19 patients ms available aim study construct score evaluate performancemethodsdata patients ms infected covid19 italy turkey south america extracted musc19 platform imputation missing values data separated training data set 70 validation data set 30 univariable logistic regression models performed training dataset identify main risk factors included multivariable logistic regression analyses select relevant variables applied three different approaches 1 multivariable stepwise 2 lasso regression 3 bayesian model averaging three scores defined linear combination coefficients estimated models multiplied corresponding value variables higher scores associated higher risk severe covid19 course performances three scores compared validation dataset based area roc curve auc optimal cutoff calculated training dataset score best performance probability showing severe covid19 course calculated based score best performanceresults3852 patients included study 2696 training dataset 1156 validation data set 17 patients required hospitalization risk factors severe covid19 course older age male sex living turkey south america instead living italy presence comorbidities progressive ms longer disease duration higher expanded disability status scale methylprednisolone use anticd20 treatment score best performance one derived using lasso selection approach auc 072 built following variables age sex country bmi presence comorbidities edss methylprednisolone use treatment excel spreadsheet calculate score probability severe covid19 available following link https osfio ac47u view_only691814d57b564a34b3596e4fcdcf8580conclusionsthe originality study consists building useful tool quantify individual risk covid19 severity based patients characteristics due modest predictive ability need external validation tool ready fully used clinical practice make important decisions interventions however can used additional instrument identify highrisk patients persuade take important measures prevent covid19 infection ie getting vaccinated covid19 adhering social distancing using personal protection equipment,0.0
annual urodynamic assessment patients multiple sclerosis cons abstract,0.0
epilepsy associated tuberous sclerosis case report bangladesh tuberous sclerosis bournevilles disease rare autosomal dominant disease affecting many organs like brain heart lungs eyes kidneys skin characterized neurological manifestation like epilepsy cutaneous changes formation benign lesions multiple organs symptoms apparent late childhood limits early diagnosis infancy report case 15 year old female child tuberous sclerosis,0.0
erratum multiple sclerosisassociated bacterial ligand 654 archives medical research 53 2 february 2022 157162 arcmed_2021_2713 abstract,0.0
noncompaction cardiomyopathy multiple sclerosis associated independent diseases case report noncompaction cardiomyopathy nccm associated neuromuscular disorders however little investigation association neurological diseases multiple sclerosis present case 46yearold woman history multiple sclerosis developed heart failure diagnosed noncompaction cardiomyopathy,0.0
gait stability reflects motor tracts damage early stages multiple sclerosis conclusions poorer gait stability associated corticospinal tract cst axonal loss pwms notolow disability sensitive indicator neurodegeneration,0.0
predictive value number volume demyelinating plaques treatment response patients multiple sclerosis treated infb conclusion results study showed imaging criteria provide objective tool evaluating effectiveness treatment findings indicate number volume plaques two reliable mri imaging criteria assessing therapy response number plaques less accurate volume plaques,1.0
retinal hyperreflecting foci associate cortical pathology multiple sclerosis background objectives microglia resident immune cell brain retina widespread activated white gray matter gm multiple sclerosis ms objective study evaluate presence number hyperreflecting foci hrf considered clusters activated proliferating retinal microglia association clinical radiologic disease parameters relapsingremitting ms rrms,0.0
movement disorders multiple sclerosis update background multiple sclerosis ms subset chronic primary inflammatory demyelinating disorders central nervous system closely associated various movement disorders disorders may due ms pathophysiology coincidental review describes full spectrum movement disorders ms possible mechanistic pathways therapeutic modalities,1.0
mri findings autoimmune glial fibrillary acidic protein astrocytopathy involving infratentorial case report autoimmune glial fibrillary acidic protein astrocytopathy gfapa new type autoimmune astrocytopathy first defined 2016 lack clinical understanding often misdiagnosed optic neuromyelitis multiple sclerosis report clinical mri findings elderly patient autoimmune glial fibrillary acidic protein astrocytopathy intractable vomiting first symptom brainstem showed typical vascular enhancement gfapa lacks specificity clinical mri,0.0
efficacy prolongedrelease fampridine emversus em placebo walking ability dynamic static balance physical impact multiple sclerosis quality life integrated analysis mobile enhance conclusion pooled analysis mobile enhance confirms previous evidence treatment prfampridine results clinically meaningful improvements walking mobility balance selfreported physical impact ms quality life effective across broad range pwms,0.0
case study improving energy status wheelchair athlete suppressed resting energy expenditure conclusion nutrition exercise intervention successfully restored energy status induced sustainable weight loss reduced fatigue wheelchair athlete multiple sclerosis presumed lea methods assess lea population require validation,0.0
quantitative susceptibility mapping ring nonring white matter lesions relapsing remitting multiple sclerosis conclusions susceptibility distribution lesion volumes rls remained almost constant time suggesting changes pathophysiology rls gradual process hand presence one rl along volume susceptibility nonrl qsm+ lesions significantly associated increased disability measured edss findings may strengthen role qsm assessing ms patients radiologically,0.0
statistical methodology highly variable compounds novel design approach ofatumumab phase 2 bioequivalence study article describes novel mixedscaling testing strategy combination adaptive parallelgroups bioequivalence trial test pharmacokinetic equivalence two formulations drug highly variable pharmacokinetics methodology applied phase 2 aplios study relapsing multiple sclerosis patients bioequivalence subcutaneous ofatumumab 20 mg administered via autoinjector pen test formulation versus prefilled syringe reference formulation,0.0
patients multiple sclerosis burden cost illness study conclusions study confirmed ms carries substantial burden patients society highlighting need awareness disease,0.0
evolution teriflunomide use multiple sclerosis realworld experience conclusions study confirms major evolution teriflunomide use clinical settings particularly nave patients young women,0.0
key drivers facilitators choice use mhealth technology people neurological conditions observational study conclusions people neurological conditions epilepsy ms accuracy ie ability detect symptoms greatest interest however individual differences people less accepting technology may need far greater reassurance data privacy people lower levels education value greater clinician involvement patient preferences considered designing mhealth technologies,0.0
interferon induced lupuslike reaction mycosis fungoides patient case report mycosis fungoides mf common form cutaneous tcell lymphomas interferon one treatment modalities mf patients far various side effects reported connection interferon use including lupuslike reaction relatively rare classified injectionsite reactions isr report 38yearold female history mf 2 years developed cutaneous lesions sites interferon 2b injections reports,0.0
illness perception profiles psychological physical symptoms newly diagnosed advanced nonsmall cell lung cancer conclusions new data add clinical portrayal patients coping nsclc since availability new therapies survival improvements disease groups reported predominance positive perceptions rather ones significant cognitive emotional struggles found illness perception data may provide contentrich resources intervention tailoring psycinfo database record c 2022 apa rights reserved,0.0
reactive astrocytes derived human induced pluripotent stem cells suppress oligodendrocyte precursor cell differentiation astrocytes instrumental maintaining central nervous system cns homeostasis responding injury major limitation studying neurodegenerative diseases like multiple sclerosis ms lack human pathological specimens obtained acute stages thereby relegating research postmortem specimens obtained years initiation pathology rodent reactive astrocytes shown cytotoxic neurons oligodendrocytes may differ human cells,0.0
spelling errors brief computermediated texts implicitly lead linearly additive penalties trustworthiness conclusion participants rated information multiple sclerosis context mimicking online health forum implicitly assigned typographic errors nearly linearly additive trustworthiness penalties contravenes dichotomous heuristic local ceiling effect trustworthiness penalties numbers typographic errors supports integrative model psychological judgments trustworthiness,0.0
edaravone inhibits production reactive oxygen species phagocytosis pkcstimulated granulocytes multiple sclerosis patients edaravone modulate oxidative stress multiple sclerosis conclusion findings suggest involvement edv rospkcnox signaling pathways modulating oxidative stress ms edv represents promising treatment option control oxidative innate immune response ms,0.0
fatty acid metabolism t cells multiple sclerosis cellular metabolic remodeling intrinsically linked development activation differentiation function survival t cells t cells transition catabolic nave state anabolic effector state upon t cell activation subsequently specialization t cells t helper th subsets including regulatory t cells t reg requires finetuning metabolic programs better support optimize t cell functions particular environment increasingly studies,0.0
downregulation vascular hemeoxygenase1 leads vasculopathy systemic sclerosis systemic sclerosis ssc terminal disease characterized vasculopathy tissue fibrosis autoimmunity although exact etiology ssc remains unknown endothelial dysfunction oxidative stress calcium handling dysregulation associated large number sscrelated complications neointima formation vasculogenesis pulmonary arterial hypertension impaired angiogenesis cardiac arrhythmias hemeoxygenase1 ho1 antioxidant enzyme involved,0.0
infection epstein barr virus increases risk multiple sclerosis causes multiple sclerosis unclear viral infection proposed possible trigger longitudinal analysis large cohort published science found risk multiple sclerosis increased 32fold following infection epsteinbarr virus ebv,0.0
associations diet quality depression anxiety fatigue multiple sclerosis abstractbackgroundmany people multiple sclerosis ms modify dietary intake post diagnosis little evidence dietary modifications influence ms outcomesmethodspeople first clinical diagnosis central nervous system demyelination followed annually 10 years depression anxiety fatigue assessed 5and 10year reviews using hospital anxiety depression scale fatigue severity scale respectively dietary intake preceding 12 months assessed baseline 5and 10year reviews using food frequency questionnaire used australian recommended food score arfs diet quality tracker dqt assess diet qualityresultsa higher diet quality previous 12 months using arfs score dqt associated lower levels depression eg highest vs lowest quartile 135 95ci244 026 p001 neither score associated anxiety fatigue assessing diet quality prospectively outcomes five years later found higher arfs score dqt score associated lower levels subsequent anxiety depression highest vs lowest quartile anxiety 161 95ci276 046 p001 depression 125 95ci244 007 p004 fatigue associations observed diet quality subsequent change depression anxiety five years although association observed diet quality change fatigue eg highest vs lowest dqt quartile 106 95ci192 021 p002 examining cumulative effect diet quality across study period 10year outcomes cumulative dqt score associated depression anxiety fatigueconclusionwe found significant inverse associations diet quality depression anxiety effect sizes modest lack consistency two diet quality measures arfs dqt diet measure correlates diet quality might underlie observed associations,1.0
comparative efficacy relapsing multiple sclerosis therapies modelbased metaanalyses confirmed disability accumulation annualized relapse rate abstractbackgroundmultiple sclerosis ms inflammatory autoimmune disorder common cause nontraumatic disability young adults phase 3 optimum study evaluated efficacy safety oral ponesimod selective sphingosine1phosphate s1p receptor 1 immunomodulator vs teriflunomide patients relapsing multiple sclerosis rms aim analysis assess effect ponesimod disease modifying treatments dmts compared placebo measured 12week confirmed disability accumulation cda annualized relapse rate arr rms patientsmethodsa database developed certara inc usa based relevant clinical trials identified searching following sources pubmed clinicaltrialsgov fda emea documents conference abstracts database consisted 203 unique randomized controlled trials rcts 74 ms treatments subsequently filtered include rcts 25 patients receiving monotherapy treat rms least 48 weeks modelbased metaanalysis mbma performed filtered database assess treatment effects measured cda arr analyzed data cda digitized published kaplanmeier plots weibull distribution assumed adequately capture relationship cda probability time hazard ratios hrs treatments assumed constant time proportional hazards hrs estimated 12week cda 17 dmts vs placebo additionally mean arr treatment arm modelled relative effect versus placebo estimated fixed effect parameter unique drug doseresponse relationship included data multiple doses available relative treatment effect covariates explored cda arr included percent patients relapsingremitting ms rrms trial start year mean duration disease percent patients received dmts within prior 2 years pdmt mean number relapses prior year mean age mean baseline edss score mean treatment duration arr resultsthe 12week cda model utilized longitudinal data 26 rcts 18 unique treatments including placebo 69 treatment arms 31 160 patients arr model utilized data 40 rcts 18 unique treatments including placebo 100 treatment arms 33 686 patients compared placebo ponesimod significantly reduced 12week cda 39 hr 061 95 ci 045082 reduced arr 53 rr 047 95 ci 039058 except three dmts interferon 1b glatiramer acetate ozanimod hr 12week cda vs placebo significantly lower dmts included analysis hr range 041 079 arr significantly reduced dmts compared placebo rr range 029 082 doseresponse relationship indicated potential dosedependent effect 12week cda 6 treatments arr 8 treatments relative treatment effect found significantly smaller trials including patients prior dmt usage crosstrial heterogeneity relative effects assessed found negligible however possibility confounders remain may impact estimated relative treatment effectsconclusionscompared placebo ponesimod 20 mg significantly reduced risk 12week cda mean arr suggesting robust efficacy treatment rms study funded janssen research development llc,0.0
associations diet quality depression anxiety fatigue multiple sclerosis abstractbackgroundmany people multiple sclerosis ms modify dietary intake post diagnosis little evidence dietary modifications influence ms outcomesmethodspeople first clinical diagnosis central nervous system demyelination followed annually 10 years depression anxiety fatigue assessed 5and 10year reviews using hospital anxiety depression scale fatigue severity scale respectively dietary intake preceding 12 months assessed baseline 5and 10year reviews using food frequency questionnaire used australian recommended food score arfs diet quality tracker dqt assess diet qualityresultsa higher diet quality previous 12 months using arfs score dqt associated lower levels depression eg highest vs lowest quartile 135 95ci244 026 p001 neither score associated anxiety fatigue assessing diet quality prospectively outcomes five years later found higher arfs score dqt score associated lower levels subsequent anxiety depression highest vs lowest quartile anxiety 161 95ci276 046 p001 depression 125 95ci244 007 p004 fatigue associations observed diet quality subsequent change depression anxiety five years although association observed diet quality change fatigue eg highest vs lowest dqt quartile 106 95ci192 021 p002 examining cumulative effect diet quality across study period 10year outcomes cumulative dqt score associated depression anxiety fatigueconclusionwe found significant inverse associations diet quality depression anxiety effect sizes modest lack consistency two diet quality measures arfs dqt diet measure correlates diet quality might underlie observed associations,1.0
pandemic changed treatment strategy multiple sclerosis abstractbackground social distancing measures covid19 pandemic reduced access health care concerns raised safety immunosuppressive disease modifying treatments dmt multiple sclerosis ms objective investigate changes dmt prescription pandemic large wellcharacterized realworld cohort ms patientsmethods vienna ms database vmsd extracted ms patients initiated new dmt treatmentnave switching january 1st 2017 december 31st 2021 two time periods defined 1 precovid19 era january 1st 2017 march 15th 2020 ie day first lockdown austria covid19 era march 16th 2020 december 31st 2021 average annualized dmt prescription rates descriptively compared two periodsresults average annualized number prescriptions precovid19 era 903 year dropped 748 year 172 covid19 era driven marked reduction 417 year 54 first nine months covid19 era partly offset rise 101 2021 use alemtuzumab 64 anticd20 49 cladribine 46 s1pm 38 reduced natalizumab increased 24 lower efficacy treatments remained stableconclusions pandemic coincides drop dmt prescription markedly immunosuppressive highefficacy treatments strongly suggesting pandemic causal factor much affects longterm outcome yet determined,0.0
role voltagegated k+ channels k2p channels intrinsic electrophysiological properties saltatory conduction nodes ranvier rat lumbar spinal ventral nerves ion channels nodes ranvier nrs believed play essential roles intrinsic electrophysiological properties saltatory conduction action potentials ap nrs myelinated nerves recently shown twopore domain potassium k2p channels play key role nrs aafferent nerves k+ channels functions nrs mammalian motor nerves remain elusive addressed issue using ex vivo preparations lumbar spinal ventral nerves male female rats pressurepatchclamp recordings nrs found depolarizing voltages evoked large noninactivating outward currents nrs outward currents partially inhibited voltagegated k+ channel blockers largely inhibited k2p blockers cooling temperatures inhibition outward currents voltagegated k+ channel blockers k2p blockers cooling temperatures significantly altered electrophysiological properties measured nrs including resting membrane potential input resistance ap width ap amplitude ap threshold ap rheobase furthermore k2p blockers cooling temperatures significantly reduced saltatory conduction velocity success rates aps response highfrequency stimulation voltagegated k+ channel blockers reduced ap success rates highfrequency stimulation without significantly affecting saltatory conduction velocity collectively k2p voltagegated k+ channels play significant roles intrinsic electrophysiological properties saltatory conduction nrs motor nerve fibers rats effects cooling temperatures saltatory conduction least partially mediated k2p channels nrssignificance statemention channels localized nrs believed key determinants saltatory conduction myelinated nerves however ion channels functions nrs fully studied different types mammalian myelinated nerves use pressurepatchclamp recordings show k2p voltagegated k+ channels play significant roles intrinsic electrophysiological properties saltatory conduction nrs lumbar spinal ventral nerves rats furthermore cooling temperatures exert effects saltatory conduction via inhibition ion channels nrs results provide new insights saltatory conduction myelinated nerves may physiological well pathological implications,1.0
slowly expanding lesions relate persisting blackholes clinical outcomes relapseonset multiple sclerosis conclusions sels associated accumulation destructive pathology indicated association pbh volume longitudinal reduction t1 intensity mtr higher sel volumes associated clinical progression lower ones associated stability relapseonset ms,0.0
validity responsiveness score interpretation promisnq physical function multiple sclerosis 15a short form multiple sclerosis conclusion promisnq pf ms 15a demonstrated reliability validity sensitivity change input patients clinicians ensured content comprehensive relevant people ms,0.0
sudomotor dysfunction people neuromyelitis optica spectrum disorders conclusions sudomotor dysfunction common pwnmosd often symptomatic compared pwrrms,0.0
patterns utilization expenditure across multiple sclerosis diseasemodifying therapies retrospective cohort study using claims data commercially insured population united states 20102019 conclusion dmt cost key driver overall healthcare expenditure ms future comparative costeffectiveness studies integrating claims electronic health records data better balancing patient characteristics warranted,0.0
plasma 24hydroxycholesterol associated narrower common carotid artery greater flow velocities relapsing multiple sclerosis abstractbackground multiple sclerosis ms studies suggest greater cardiovascular disease burden disturbances cholesterol pathways potential impact oxidized cholesterol molecules oxysterols ms emergingobjective determine relationship multiple oxysterol molecules atherosclerosis burden ms patientsmaterials methods total 99 ms patients 61 relapsingremitting ms rrms 38 progressive ms pms patients 38 healthy controls hcs underwent magnetic resonance angiography mra crosssectional area csa common carotid artery cca determined three different levels bifurcation c7 c6 c5 additionally echocolor doppler ultrasound performed measures blood flow velocities derived blood samples acquired time imaging examinations analyzed 24 25 27hydroxycholesterol 24hc 25hc 27hc 7ketocholesterol 7kc quantified ng mlresults ms patients higher levels 24hc significantly associated smaller cca csa measured three cervical levels r0201 p0046 r0228 p0023 r0215 p0032 c7 c6 c5 respectively associations driven rrms group r0407 p0002 c7 r0414 p0002 c6 r0368 p0006 c5 associations seen hcs despite adjusting significant age effect b0445 p0004 higher 24hc levels independently associated smaller cca csa b020 p0045 24hc additionally associated greater timeaveraged peak diastolic cca velocities rrms patients treated potent antiinflammatory therapies lower oxysterol levels p0019 conclusion greater 24hc levels associated smaller csa cca greater flow velocities rrms patients,0.0
feedback neurology residents neuroimmunology fellows practical training multiple sclerosis conclusion number patients medical records use ms clinical scales discussion attending neurologist specialized ms care prescription dmds present room improvement ms training neurology residents neuroimmunology fellows,0.0
cuprizonemediated demyelination reversibly degrades voiding behavior mice sparing brainstem reflex multiple sclerosis ms chronic progressively debilitating demyelinating disease central nervous system cns nearly 80 ms patients experience lower urinary tract dysfunction early diagnosis significantly affects quality life latter stages disease leading cause hospitalization previously animal models shown inflammatory demyelination cns causes profound bladder dysfunction confounding influence systemic,1.0
onset multiple sclerosis preventable time act now abstract,0.0
tixagevimab cilgavimab evusheld boosts antibody levels sarscov2 patients multiple sclerosis bcell depleters abstractbackground objectivesbcelldepleting therapies may affect development protective immune response following vaccination sarscov2 important different strategy creating immunity patient population objective study evaluate whether evusheld tixagevimab copackaged cilgavimab affects antibody response sarscov2 following attenuated response vaccines sarscov2 patients bcell depleters multiple sclerosismethodsthis singlecenter cohort study performed methodist hospitals merrillville usa included patients multiple sclerosis treated ocrelizumab ofatumumab patients already received mrna vaccinations sarscov2 demonstrated attenuated response baseline antibody testing participants received 150mg evusheld followup antibody levels measured least two weeks following evusheld injectionsresultsall patients 100 developed highest level antibodies possible least two weeks following evusheld injectionsdiscussionin study patients ms attenuated antibody response covid19 vaccines due exposure bcell depleters now highest antibody response possible receiving evusheld important provides different strategy protection covid19,0.0
rare antibodymediated seronegative autoimmune encephalitis update paralleling advances respect common antibodymediated encephalitides antinmethyldaspartate receptor nmdar antileucinerich gliomainactivated 1 lgi1 abmediated encephalitis discovery characterisation novel antibodymediated encephalitides accelerated past decade adding depth etiologically spectrum antibodymediated encephalitis herein review major mechanistic clinical features management considerations,0.0
late onset neuromyelitis optica spectrum disorders lonmosd nationwide portuguese study antiaqp4 positive antimog positive seronegative subgroups conclusions lonmosd increased disability faster progression despite differences presenting clinical phenotype seen cohort,0.0
nurr1deficient mice age sexspecific behavioral phenotypes transcription factor nurr1 essential generation maintenance midbrain dopaminergic mda neurons deregulation involved development dopamine da associated brain disorders parkinsons disease pd old male nurr1 heterozygous knockout nurr1ko mouse proposed model pd due altered motor performance however confirmed subsequent study based controversial results explored effects,0.0
autologous hematopoietic stem cell transplantation multiple sclerosis ottawa protocol autologous hematopoietic stem cell transplantation ahsct increasingly used treat patients highly active multiple sclerosis ms refractory diseasemodifying therapy briefly cyclophosphamide filgrastim used mobilize autologous hematopoietic stem cells hsc circulation hsc harvested leukapheresis purified using cd34 immunomagnetic selection process cryopreserved busulphan cyclophosphamide rabbit antithymocyte globulin used,0.0
implications lower extremity muscle power force walking fatigability multiple sclerosis exploratory pilotstudy background limitations physical function common multiple sclerosis ms yet neither clear muscle power implicates physical function walkingfatigability pilotstudy aims investigate 1 deficits muscle power force alongside walking persons ms 2 associations muscle power force physical functions 3 impact prolonged walking muscle power force,0.0
analysis dynamic gene expression patterns peripheral blood multiple sclerosis patients indicates possible diagnostic prognostic biomarkers conclusion study exhibits dynamic gene expression patterns represent significance specified genes prospective diagnostic prognostic biomarkers multiple sclerosis,0.0
relationship smoking multiple sclerosis severity saudi arabia introduction multiple sclerosis ms autoimmune disease can disabling patients smoking proposed risk factor ms increase risk progression disease severity however still clear smoking affects people ms pwms regarding disease phenotype symptoms relapses course disability aim study investigate effect smoking pwms saudi arabia methods online,0.0
rummeliibacillus suwonensis first time isolation human feces culturomics gut microbiota complex ecosystem composed trillions microorganisms crucial human health disease status currently two methodological options explore complexity metagenomics culturomics culturomics approach uses multiple culture conditions days incubation enrichment factors growth temperature malditof mass spectrometry identification bacterial species sequencing method fails paper,0.0
inclusion societal costs change economic evaluations recommendations systematic review multiple sclerosis disease conclusions inclusion social costs affected results conclusions multiple sclerosisrelated interventions helping identify appropriate interventions reducing economic burden broader perspective,0.0
realworld evidence study nabiximols multiple sclerosis patients resistant spasticity analysis relation newlydescribed spasticityplus syndrome conclusion realworld analysis supports concept spasticityplus syndrome suggests nabiximols can favorably impact range spasticityassociated symptoms,1.0
myeloid cellspecific topoisomerase 1 inhibition using dna origami mitigates neuroinflammation targeting myeloid cells especially microglia treatment neuroinflammatory diseases multiple sclerosis ms underappreciated silico drug screening reveals topoisomerase 1 top1 inhibitors promising drug candidates microglial modulation show top1 highly expressed neuroinflammatory conditions top1 inhibition using camptothecin cpt fdaapproved analog topotecan tpt reduces inflammatory responses microglia macrophages,1.0
school performance psychiatric comorbidity juvenile absence epilepsy juvenile myoclonic epilepsy danish populationbased cohort study conclusions jae jme marginally poorer school performance performance seemed worse jae jme jae jme increased use sleep medication,0.0
multiple sclerosis patients hereditary spastic paraplegia case report systematic review conclusion first description association spg3a type hsp ms report adds reported cases cooccurring hsps ms although remains unclear association casual causal clinicians aware hsp diagnosis always exclude concomitant ms,0.0
hlagenotyping nextgenerationsequencing reveals shared unique hla alleles two patients coexisting neuromyelitis optica spectrum disorder thymectomized myasthenia gravis immunological implications mutual aetiopathogenesis exact immunopathogenesis genetic mechanisms triggering factors underlying myasthenia gravis mg neuromyelitis optica nmo remain unknown coexistence may underline aetiopathogenetic link tween two diseases report cases two thymectomized patients acetylcholine receptor achr antibody ab positive mg eventually developed aqp4nmo nextgeneration sequencing ngs analysis showed patient1 two hla alleles previously associated,0.0
evaluating feasibility real world pharmacovigilance study optimisems abstractbackground clinical trial populations fully reflect routine practice power routinely collected data inform clinical practice increasingly recognisedmethods optimisems pharmacovigilance study prospective pragmatic observational study conducted across 13 uk ms centres data collected time routine clinical visits first participant recruited 24th may 2019 data extracted 11th november 2021results 2112 participants included median age 440 years 1570 72 female 1981 94 relapsingremitting ms 639 30 untreated study entry 205 10 taking interferon beta copaxone 1004 47 second third generation dmt first line 264 13 escalated platform dmt 342 clinical events reported 108 infections increased risk adverse events people taking second third generation dmt rr 345 95ci 157760 p001 vs dmt unadjusted poisson regression demonstrated increased incident adverse events people taking natalizumab irr 528 95ci 1411974 p005 ocrelizumab irr 324 95ci 122862 p005 ga biosimilar brabio irr 489 95ci 1311821 p005 vs dmtconclusions routinely collected healthcare data can used evaluate dmt safety people ms data highlight potential pragmatic studies guide understanding risks benefits associated dmt,0.0
targeting epsteinbarr virus treat ms epsteinbarr virus ebv putative trigger multiple sclerosis ms bjornevik et al utilized longitudinal analysis 10 million adults strongly link ms ebv infection lanz et al identified clonally expanded b cells ms bind ebv ebna1 glialcam,0.0
stat1 signaling protects selfreactive t cells control innate cells neuroinflammation transcription factor signal transducer activator transcription 1 stat1 plays critical role modulating differentiation cd4+ t cells producing il17 gmcsf promote development experimental autoimmune encephalomyelitis eae animal model multiple sclerosis ms protective role stat1 ms eae largely attributed ability limit pathogenic t helper th cells promote regulatory t treg cells using mice selective,1.0
therapeutic potential astrocyte purinergic signalling epilepsy multiple sclerosis epilepsy multiple sclerosis ms two common neurological diseases characterized establishment inflammatory environment central nervous system drives disease progression impacts neurodegeneration current therapeutic approaches treatments epilepsy ms targeting neuronal activity immune cell response respectively however lack fully efficient responses available treatments obviously shows need search,1.0
postalemtuzumab graves disease remitting switch ocrelizumab abstract,0.0
efficacy different intensity aquatic exercise enhancing remyelination neuronal plasticity using cuprizone model male wistar rats conclusions general fitness achieved preconditioning program combined hie showed neuroprotective effects evidenced increased areas remyelination improved neuronal plasticity observed mostly group vi conditioning+hie,1.0
antinuclear antibodies positivity rare multiple sclerosis associated relapsing status igg oligoclonal bands positivity conclusion results showed ana positivity ms disease rare positivity associated clinical expression connective tissue disease ana occurrence ms associated igg ocb+ profile relapsing status probably reflecting ongoing immune dysregulation,0.0
concurrent cns tumors multiple sclerosis retrospective singlecenter cohort study lessons clinical management conclusions study describes clinical demographic features patients concurrent cns tumors ms suggests several practical approaches clinical management findings suggest adding diseasemodifying ms therapy regimen patients treated chemotherapy necessary patient suffers highly active aggressive course ms view lack prospective trials individual risk assessments remain foundation,0.0
sleep pain neurodegeneration mendelian randomization study aim determine whether genetic liability sleep painrelated traits causal effect risk neurodegeneration individuals predominantly european ancestry selected five neurodegenerative disorders namely agerelated macular degeneration amd alzheimers disease ad amyotrophic lateral sclerosis als multiple sclerosis ms parkinsons disease pd sleep duration sd short sleep ss long sleep ls chronotype chr morning person mp,0.0
dietary supplementation emacer truncatum em oil promotes remyelination mouse model multiple sclerosis conclusion diet supplementation acer truncatum oil attenuates demyelination induced cuprizone indicating acer truncatum oil novel therapeutic diet demyelinating diseases,1.0
chronic inflammatory demyelinating polyneuropathy unique case chronic disease atypical features present unique case diffusely extensive chronic inflammatory demyelinating polyneuropathy cidp typically affecting peripheral nervous system manifesting muscle weakness breakdown paresthesia present case additionally demonstrates cranial nerve involvement central nervous system parenchymal lesions chronic osseous remodeling nerve tracts cranial nerve involvement extent described one case report knowledge,1.0
therapeutic strategy multiple sclerosis resistant standard treatment ms cases relapses controlled standard treatment eight diseasemodifying drugs approved treating multiple sclerosis japan drugs show differences degree prevent relapses among natalizumab ofatumumab significantly effective preventing relapses relapses suppressed treated natalizumab presence antinatalizumab antibodies investigated relapses suppressed natalizumab patient treated ofatumumab,0.0
role noncoding rnas neuroinflammatory process multiple sclerosis multiple sclerosis ms central nervous system chronic neuroinflammatory disease followed neurodegeneration diagnosis based clinical presentation cerebrospinal fluid testing magnetic resonance imagining still lack diagnostic bloodbased biomarker ms due cost difficulty diagnosis new easily accessible methods sought new biomarkers also allow early diagnosis additionally treatment ms lead,0.0
differential regulation mouse hippocampal gene expression sex differences chromosomal content gonadal sex common neurological disorders like alzheimers disease ad multiple sclerosis ms autism display profound sex differences prevalence clinical presentation however sex differences brain health disease often overlooked experimental models sex effects originate directly indirectly hormonal sex chromosomal mechanisms delineate contributions genetic sex xx v xy versus gonadal sex ovaries v testes epigenomic regulation,0.0
therapeutic strategy multiple sclerosis resistant standard treatment refractory ms japan diseasemodifying drugs multiple sclerosis amounted eight date providing us various therapeutic choices however still encounter difficult cases resistant drugs review summarizes diagnostic therapeutic strategies refractory multiple sclerosis presenting suggestive cases,0.0
disability progression spms despite therapeutic intervention refractory spms new diseasemodifying drugs dmds ocrelizumab siponimod proven efficacious treating progressive multiple sclerosis ms marked new era treatment disease however drugs work inflammatory component disease potential effect neurodegenerative aspect ms likely modest therefore treatment progressive ms continues challenging routine clinical practice review summarizes,0.0
choroidal thickness multiple sclerosis optical coherence tomography study conclusions ct differ ms control eyes significantly larger patients history rnfl thinner studies necessary establish possible role choroid ms,0.0
disability progression spms despite therapeutic intervention current status perspectives treatment diseasemodifying drugs currently siponimod diseasemodifying drugs dmds proven efficacy safety clinical trials secondary progressive multiple sclerosis spms however efficacy siponimod preventing disability progression insufficient yet able deter disability progression therefore considered necessary use dmds high relapsepreventive effect relatively early stage spms disease activity remains evident brutons tyrosine,0.0
antidrug antibodies biological treatments multiple sclerosis development antidrug antibodies adas major problem several recombinant protein therapies used treatment multiple sclerosis ms etiology adas multifaceted predisposition breakdown immune tolerance probably genetically determined many factors may contribute immunogenicity including structural properties formation aggregates presence contaminants impurities industrial manufacturing process adas may,0.0
patients myalgic encephalomyelitis chronic fatigue syndrome cfs already visited medical institutions diagnosis treatment research myalgic encephalitis chronic fatigue syndrome cfs acquired intractable disease characterized profound fatigue postexertional malaise sleep disturbance cognitive impairment orthostatic intolerance among features onset often follows infectious episode importantly various types autonomic dysfunctions pain intolerance various stimuli cfs patients intrinsically different fatigue healthy individuals short essay,0.0
clinical radiological features myelin oligodendrocyte glycoproteinassociated myelitis adults antibodies myelin oligodendrocyte glycoprotein mogigg recently established biomarker mogantibodyassociated disease mogad distinct demyelinating disease central nervous system among diverse clinical phenotypes mogad myelitis secondmostcommon presentation adults followed optic neuritis features overlap multiple reports distinctive clinical radiological features mogiggassociated,1.0
remyelination humans due retinoidx receptor agonist agedependent remyelination efficiency declines advancing age animal models harder demonstrate people multiple sclerosis show bexarotene putatively remyelinating retinoidx receptor agonist shortened visual evoked potential latency patients chronic optic neuropathy aged 42 years effect diminishing 045 ms per year age increased magnetization transfer ratio deep gray matter lesions 43 years,1.0
multiple sclerosis systemic challenges costeffective care conclusion insurers neurologists researchers patient advocacy groups must address needs patients ms holistically efforts include establishing standards mri machines reports matching patients ms specialists aligning financial incentives including creating new cpt code complex brain mri streamlining prior authorization processes dmts using technology gather patient data improve coordination care developing better,0.0
association persistence adherence diseasemodifying therapies healthcare resource utilization costs patients multiple sclerosis background persistence adherence diseasemodifying therapies dmts affects treatment efficacy economic outcomes contribute overall patient disease burden current literature suggests patients multiple sclerosis ms adhere dmt 12 months fewer relapses reduced msrelated healthcare resource utilization hcru medical costs nonadherent patients objective expand previous research estimating association,0.0
impact covid19 people multiple sclerosis comparison italian united states cohorts abstractbackground objectivesthe present crossnational study addressed relationship among three pandemicrelated variables multiple sclerosis ms disability outcomes among people ms italy united states us methodsthis crosssectional webbased study administered 708 patients ms us italy late spring midsummer 2020 pandemicrelated variables assessed worry selfprotection posttraumatic growth performance scales assessed ms disability multivariate multiple regression models addressed separately country relationship among worry protection posttraumatic growth ms disability covariate adjustmentresultsthe italian sample n292 younger less disabled us group n416 covariate adjustment three pandemicrelated variables associated ms disability outcomes us sample worry posttraumatic growth associated italian sample worse cognitive depression symptoms associated worry lesser mobility disability associated endorsed growth countries disability variables associated worry growth italian sampleconclusionsthe pandemics negative aspects associated worse disability countries reported posttraumatic growth associated lesser disability findings may suggest directions clinical intervention,0.0
comparative effectiveness four exercise interventions followed two years exercise maintenance multiple sclerosis randomized control trial conclusion 25 sessions exe bal cyc pnf order improved clinical motor symptoms qol subsequent 2ylong thrice weekly maintenance programs slowed symptomworsening improved qol exe pnf least effective improve clinical symptoms motor function qol pwms,0.0
major depression favors expansion th17like cells decrease proportion cd39sup+ suptreg cell subsets response myelin antigen multiple sclerosis patients conclusions summary findings suggested recurrent major depression favoring imbalances effector th17 treg cell subsets contributes ms severity,1.0
clinical spectrum haemorrhagic cns inflammatory demyelinating lesions conclusion lesional haemorrhage uncommon demyelinating disease closely associated ahl bleeding within demyelinating lesion always herald poor prognosis,1.0
smartphonebased gait balance assessment survivors stroke systematic review conclusion preliminary evidence supports smartphonebased gait balance assessments valid reliable sensitive specific ss laboratory settings future research needed test smartphonebased gait balance assessments home settings determine optimal wear sites assessmentsimplications rehabilitationsmartphonebased gait balance assessments feasible valid reliable survivors strokethe findings may guide future research standardize,0.0
severe disease exacerbation mrna covid19 vaccination unmasks suspected multiple sclerosis neuromyelitis optica spectrum disorder case report conclusions pathogenic mechanisms postvaccination occurrence nmosd still unknown however cases like make aware rare neurological disorders manifesting vaccination potentially contribute improvement management vaccinating patients inflammatory cns disorders future far two cases aqp4antibody positive nmosd reported association viral vector covid19 vaccines knowledge report first case,0.0
serum mogigg children meeting multiple sclerosis diagnostic criteria conclusion children mogigg can clinical csf mri features conforming ms criteria presence mogigg associated atypical features predicts nonms disease course given mogigg seropositivity can wane time testing first attack considerable importance diagnosis mogad,0.0
entimos discrete event simulation model maximising efficiency infusion suites centres treating multiple sclerosis patients conclusion entimos flexible model patient flow care delivery infusion centres serving ms patients allows users simulate specific local settings therefore identify measures necessary avoid clinically significant treatment delay resulting suboptimal care,0.0
systematic review european regional national guidelines focus recommended use nabiximols management spasticity multiple sclerosis introduction spasticity common debilitating symptom multiple sclerosis ms several treatment options including cannabinoidbased treatment nabiximols purpose review examine existing clinical practice guidelines direct management multiplesclerosisassociated spasticity mss identify areas similarity divergence suggest standardization improvement may obtained,0.0
intimate partner violence women living episodic disabilities scoping review protocol background violence towards women disabilities commonly perpetrated current former intimate partners half disabled women experience intimate partner violence lifetime disabilities differ presence type complexity yet commonly researched collectively nuanced understanding relationship intimate partner violence episodic disability required better support women living concurrent challenges,0.0
postmortem correlates virchowrobin spaces detected emin vivo em mri purpose study quantify extent virchowrobin spaces vrs detected vivo mri reproducible postmortem mridouble echo steady state 3t mris acquired postmortem 49 double 32 singlehemispheric formalinfixed brain sections 12 patients underwent conventional diagnostic 15 3t mri median 22 days prior death 25 75 12 134 days overlap vivo postmortem vrs segmentations determined accounting,0.0
effect drugs progressive ms due effect inflammation subgroup metaanalysis randomised trials conclusions study showed benefit treating patients pms mostly confined active disease drugs targeting specific pathological processes leading disability progression remain necessary,0.0
altered grey matter integrity network vulnerability relate epilepsy occurrence patients multiple sclerosis conclusions high lesion load altered integrity mesiotemporal gm structures network reorganization associated greater propensity epilepsy occurrence ms,0.0
ocrelizumab multiple sclerosis background ocrelizumab humanised anticd20 monoclonal antibody developed treatment multiple sclerosis ms approved food drug administration fda march 2017 using adults relapsingremitting multiple sclerosis rrms primary progressive multiple sclerosis ppms ocrelizumab diseasemodifying therapy dmt approved ppms november 2017 european medicines agency ema also approved ocrelizumab first drug,0.0
confirmed disability progression marker permanent disability multiple sclerosis conclusions clinicodemographic characteristics 6month confirmed disability progression events identify high risk sustained longterm disability knowledge will allow future trials better assess effect therapy longterm disability accrual,0.0
assessment 2d conventional synthetic mri multiple sclerosis conclusion synthetic mri can potentially used alternative conventional brain mri sequences assessment ms,0.0
free vitamin dsub3 sub index vitamin dbinding protein multiple sclerosis presymptomatic casecontrol study conclusions findings support hypothesis high levels free 25 oh d 3 young age reduces risk ms later life also implicate role dbp ms aetiology,0.0
beyond canvas behavioral onset rfc1expansion disease italian familycausal casual conclusion behavioralcognitive observations may broaden rfc1expansion phenotypic spectrum highlight importance investigating whole nonmotor symptoms ataxic patients,0.0
incidence prevalence diagnosis treatment multiple sclerosis china narrative review 2018 first list rare diseases published national health council china multiple sclerosis ms included list since chinese government neurologists made efforts improve clinical outcomes patients ms last years incidence ms china also investigated early accurate diagnosis ms improved due application promotion magnetic resonance imaging new diagnosis criteria,0.0
effect cognitive performance selfmanagement behavior multiple sclerosis patients abstractbackgrounddifficulties selfmanagement people ms pwms considered one important factors contributing low rehabilitation efficacy severe longterm complications increase healthcare costs despite emergence research last decade documenting causes types course cognitive difficulties ms disease subtypes limited evidence available literature direct comparison selfmanagement cognitive deficits study aimed investigate relationship cognitive performance selfmanagement pwmsmethodspwms applied neurology outpatient clinics seven different centers included study multiple sclerosis selfmanagement scale revised mssmr used assessment selfmanagement behaviors multiple sclerosis inventory cognition scale music used assessment cognitive performance fatigueresultsin study 194 144 female 50 male pwms participated mean age389 years course disease rrms 173 patients mean edss 20 685 participants married 325 employed 572 secondary education mssmr mean score study group 426104 181 positive correlation mssmr musiccog scores r021 p0003 hierarchical multiple regression revealed income level 0196 t2692 p0008 cognitive performance 0167 t2063 p0041 together control variables gender age educational status employment status duration disease edss fatigue explained 55 variance selfmanagementconclusioncognitive performance predictor selfmanagement pwms better selfmanagement behavior also related employment income level pwms studies evaluating patients cognitive abilities evaluating effectiveness adapted selfmanagement training programs needed,0.0
effect cognitive performance selfmanagement behavior multiple sclerosis patients abstractbackground difficulties selfmanagement people ms pwms considered one important factors contributing low rehabilitation efficacy severe longterm complications increase healthcare costs despite emergence research last decade documenting causes types course cognitive difficulties ms disease subtypes limited evidence available literature direct comparison selfmanagement cognitive deficits study aimed investigate relationship cognitive performance selfmanagement pwmsmethods pwms applied neurology outpatient clinics seven different centers included study multiple sclerosis selfmanagement scale revised mssmr used assessment selfmanagement behaviors multiple sclerosis inventory cognition scale music used assessment cognitive performance fatigueresults study 194 144 female 50 male pwms participated mean age389 years course disease rrms 173 patients mean edss 20 685 participants married 325 employed 572 secondary education mssmr mean score study group 426104 181 positive correlation mssmr musiccog scores r021 p0003 hierarchical multiple regression revealed income level 0196 t2692 p0008 cognitive performance 0167 t2063 p0041 together control variables gender age educational status employment status duration disease edss fatigue explained 55 variance selfmanagementconclusion cognitive performance predictor selfmanagement pwms better selfmanagement behavior also related employment income level pwms studies evaluating patients cognitive abilities evaluating effectiveness adapted selfmanagement training programs needed,0.0
chronic cortical inflammation cognitive impairment immune reactivity associated diffuse brain injury ameliorated forced turnover microglia ,1.0
bloodbrain barrier permeability changes first year alemtuzumab treatment predict 2year outcomes relapsingremitting multiple sclerosis abstractbackground relapsingremitting multiple sclerosis rrms early disease control reduces risk permanent disability bloodbrain barrier bbb compromised ms permeability potential biomarkerobjective investigate bbb permeability measured mri marker alemtuzumab efficacymethods patients rrms initiating alemtuzumab treatment recruited prospectively bbb permeability assessed patlakderived influx constant ki dynamic contrastenhanced mri 6 12 18 months first course alemtuzumab evidence disease activity3 neda3 status ascertained two years treatment initiationresults patients maintained neda3 status two years n7 larger decrease ki baseline six months 0029 ml 100g min ci 00050053 baseline 12 months normal appearing white matter 0043 ci 0022 0065 experienced disease activity n8 roc curve analysis ki change baseline 12 months nawm predicted loss neda status 2 years 86 sensitivity 86 specificity auc 098 p0002 conclusion bbb permeability predicted alemtuzumab efficacy two years indicating bbb permeability biomarker treatment response rrms,1.0
nucls scalable crowdsourcing approach dataset nucleus classification segmentation breast cancer conclusions study extensive systematic exploration largescale use wisdomofthecrowd approaches generate data computational pathology applications,0.0
effectiveness safety early highefficacy versus escalation therapy relapsingremitting multiple sclerosis argentina conclusions study shows ehe therapies prevent disease progression relapses new mri lesions demonstrated increased risk specific adverse events compared es therapy data considered selecting specific treatment ms patients,0.0
mitotically heritable rna polymerase iiindependent h3k4 dimethylation stimulates emino1 em transcriptional memory inducible genes rate molecular mechanism transcriptional activation depends prior experiences cell phenomenon called epigenetic transcriptional memory accelerates reactivation requires changes chromatin structure recruitment poised rna polymerase ii rnapii promoter memory inositol starvation budding yeast involves positive feedback loop transcription factordependent interaction nuclear pore complex,0.0
initial experience using axonics sacral neuromodulation system patients multiple sclerosis conclusion majority ms patients reported significant initial improvement uui associated quality life measures validated questionnaires implantation axonics system future studies needed determine longterm outcomes durability mri fullbody conditionallysafe system,1.0
kidney biopsy features predictive clinical outcomes spectrum minimal change disease focal segmental glomerulosclerosis conclusions predictive descriptors clinical outcomes among mcd fsgs patients reflected structural changes multiple renal compartments reporting descriptors standardized guide prognostication proteinuric glomerular diseases,0.0
systemic management brain metastases her2+ breast cancer 2022 half patients metastatic human epidermal growth factor receptor 2positive her2+ breast cancer will eventually acquire brain metastases brms associated reduced overall survival decreased quality life although median overall survival previously less year novel systemic treatments significantly extended life expectancy patients her2+ breast cancer brms current firstline standard care patients her2+,0.0
performance adding hepatobiliary phase image magnetic resonance imaging detection hepatocellular carcinoma metaanalysis conclusion gdeobdtpaenhanced mri hbp showed higher sensitivity without hbp comparable specificity diagnosis hcc patients chronic liver disease,0.0
provider caregiver satisfaction telehealth evaluation autism spectrum disorder young children covid19 pandemic present study examines provider caregiver satisfaction telehealth evaluation autism spectrum disorder asd young children coronavirus sarscov2 covid19 pandemic telehealth model asd evaluation implemented 308 children ages 14 78 months may 2020 june 2021 data gathered electronic health records autismspecific telehealth diagnostic tools postevaluation surveys overall majority providers caregivers,0.0
sensitivity evidential dependencies judgments uncertainty according bayesian models judgment testimony independent informants evidential value dependent testimony three experiments investigated learners sensitivity distinction experiment used social version ballsandurns task participants judged two urns likely source evidence presented multiple informants informants either provided independent testimony based solely observations,0.0
innovative animal monitoring device experimental autoimmune encephalomyelitis d eae detailed evaluation improved results conclusions considering high reproducibility interrater reliability d eae useful tool eae monitoring,0.0
openenvironment tactile sensing system towards simple efficient material identification robotic perception can simple effective sensing functions unreachable humans using isolated tactile perception method assistance triboelectric nanogenerator teng however reliability triboelectric sensors remains major challenge due inherent environmental limitations intelligent tactile sensing system combines teng deep learning technology proposed using triboelectric triple tactile sensor tts array,0.0
2021 white paper recent issues bioanalysis tab nab viral vector cdx shedding assays crispr cas9 amp cart immunogenicity pcr amp vaccine assay performance ada assay comparability amp cut point appropriateness upart 3 u recommendations gene therapy cell therapy vaccine assays immunogenicity biotherapeutics novel modalities integrated summary immunogenicity harmonization 15th edition workshop recent issues bioanalysis 15th wrib held 27 september 1 october 2021 even lastminute move inperson virtual overwhelmingly high number nearly 900 professionals representing pharma biotech companies contract research organizations cros multiple regulatory agencies still eagerly convened actively discuss current topics interest bioanalysis 15th wrib included 3 main workshops 7,0.0
recent advances dualtargetactivated fluorescent probes biosensing bioimaging fluorescent probes powerful tools visualizing quantifying multiple dynamic processes living cells however currently developed probes often constructed conjugation fluorophore recognition moiety given signaloutput triggering one singly target interest compared singletargetactivated fluorescent probes mentioned dualtargetactivated ones triggering one target stimulus photoirradiation,0.0
increased microchimerism peripheral blood women systemic lupus erythematosus relation pregnancy conclusions just delivery slepatients microchimerism control subjects three months postpartum microchimerism longer detectable reappear many years last pregnancy often higher levels slepatients control subjects suggests chimeric cells may originate noncirculating foetal chimeric stem cells,0.0
chronic diseases comorbidities adults without intellectual disabilities comparative crosssectional study dutch general practice conclusions study identified younger onset chronic illness higher prevalence multiple comorbidities among people id general practice without id underlines complexity people id chronic diseases general practice study confirmed earlier onset chronic diseases comorbidities recommended acknowledge age differences following chronic disease guidelines,0.0
promyelocytic leukemia nuclear bodylike structures can assemble mouse oocytes promyelocytic leukemia pml nuclear bodies pmlnbs class membraneless cellular organelles participate various biological activities pmlnbs known coreshelltype nuclear body harboring client proteins core although multiple membraneless organelles work oocyte nucleus pmlnbs predicted absent oocytes show wellknown pml clients endogenous pml colocalized small ubiquitinrelated modifier sumo,0.0
opportunities challenges mesenchymal stem cells treatment multiple sclerosis multiple sclerosis ms considered untreatable disease years research many drugs discovered widely used treatment ms however current treatment can alleviate clinical symptoms ms serious side effects mesenchymal stem cells mscs provide neuroprotection migrating injured tissues suppressing inflammation fostering neuronal repair therefore mscs therapy holds great promise ms treatment review,0.0
can treat neurodegenerative proteinopathies enhancing protein degradation neurodegenerative proteinopathies defined class neurodegenerative disorders either genetic sporadic agerelated onset characterized pathological accumulation aggregated protein deposits mainly include alzheimers disease ad parkinsons disease pd amyotrophic lateral sclerosis als huntingtons disease hd well frontotemporal lobar degeneration ftld deposition abnormal protein aggregates brain patients affected,0.0
combining factorial multiarm multistage platform designs evaluate multiple interventions efficiently conclusion combined factorialmams design can combine efficiencies factorial trials multiarm multistage platform trials allows us address multiple research questions one protocol test multiple new treatment options particularly important facing new emergent infection covid19,0.0
application contrastenhanced ultrasound bosniak classification diagnosis cystic renal masses conclusion ceus combined bosniak classification greatly improves diagnosis crcc ceus shows comparable diagnostic ability cect daily clinical routine patients require multiple examinations contraindications cect can particularly benefit using ceus,0.0
innate immune cellrelated pathology thalamus signals risk disability progression multiple sclerosis background objectives aim investigate whether 18kda translocator protein tspo radioligand binding gray matter gm predicts later disability progression multiple sclerosis ms,0.0
exploring vivo multiple sclerosis brain microstructural damage t1w t2w ratio multicentre study conclusions t1w t2w ratio may represent clinically relevant marker sensitive demyelination neurodegeneration iron accumulation occurring different multiple sclerosis phases,1.0
effects optimal dosage resistance training strength functional capacity balance general health perception fatigue people multiple sclerosis systematic review metaanalysis conclusions rtp improves strength functional capacity balance fatigue people ms registration prospero crd42020182781implications rehabilitationresistance training valid strategy improve isometric strength functional capacity ms patientsrtp using long durations 6 weeks high intensity 80 1rm twoday weekly training frequency may correct stimulus improve strength functional capacity balance fatigue people,0.0
transitioning s1p receptor modulators b celldepleting therapies multiple sclerosis clinical radiographic laboratory data background objectives patients multiple sclerosis ms transition oral sphingosine1receptor s1p modulators anticd20 therapies several circumstances optimal timing transition uncertain given competing concerns rebound disease activity ensuring immune reconstitution objective study evaluate relationship inflammatory activity transition period fingolimod anticd20 therapies realworld ms cohort,0.0
downregulated cylindromatosis enhances nfb activation aggravates inflammation hbvaclf patients pathogenesis liver patients hepatitis b virusassociated acute chronic liver failure hbvaclf remains largely unknown aimed elucidate molecular mechanism underlying pathogenesis liver hbvaclf patients using multiple approaches including transcriptome analysis performed transcriptomic sequencing analysis liver hbvaclf patients n 6 chronic hepatitis b n 6 liver cirrhosis n 6 normal control n 5 explored,0.0
new insights immunologic role oligodendrocyte lineage cells demyelination diseases oligodendrocyte lineage cells ollineage cells cell population crucial mammalian central nervous system cns myelination ollineage cells go developmental stages initially differentiating oligodendrocyte precursor cells opcs becoming immature oligodendrocytes mature oligodendrocytes ols main function cell lineage myelin formation increasing number studies turned explore immunological characteristics,1.0
neuromodulation lower urinary tract symptoms special populations conclusions small number studies snm ptns appear safe effective special neurological populations patients ms pd sci mri compatibility helped improve eligibility snm special populations studies looking snm limited small number subjects lack prospective trials selection bias larger randomized studies longterm follow needed better predict response snm ptns populations,0.0
involvement ageassociated b cells ebvtriggered autoimmunity ebv infection long suspected play role development autoimmune diseases interestingly recently published study provided strongest evidence date ebv truly trigger multiple sclerosis well known inflammatory neurodegenerative autoimmune disorder taking account data derived mice models autoimmune diseases also infected murine analog ebv commentary highlight involvement ageassociated,0.0
increasing incidence prevalence multiple sclerosis greater hobart cohort tasmania australia conclusions prevalence incidence ms continue increase significantly hobart alongside marked reductions mortality increased case longevity marked increase incidence particular note may reflect longstanding changes ms risk behaviours including changing sun exposure obesity rates smoking behaviours particularly females falling mortality contributes increase longevity prevalence likely reflecting improved overall ms healthcare,0.0
rare cooccurrence multiple sclerosis wilsons disease case report conclusion case presented report similar reported cooccurrence two diseases seems coincidence sharing common factors pathogenesis however considered influence one another regarding rare cooccurrences one every new case high importance enables better evaluation understanding clinical presentations characteristic cases thus aiding,0.0
association brain atrophy disease progression independent relapse activity patients relapsing multiple sclerosis conclusions relevance study shows patients rms pira exhibit accelerated brain atrophy especially cerebral cortex results point need recognize insidious manifestations pira clinical practice evaluate treatment strategies patients pira clinical trials,0.0
developments iterations mobile technologybased fall risk health application falls prevalent serious health concern across clinical populations critical step falls prevention identifying modifiable risk factors due time constraints equipment costs fall risk screening rarely performed mobile technology offers innovative approach provide personalized fall risk screening clinical populations inform future development manuscript discusses development testing mobile health fall risk applications three,0.0
cerebellar brainstem lesions indicate poor prognosis multiple sclerosis systematic review multiple sclerosis serious neurological disease affects millions people worldwide cerebellar brainstem symptoms common course multiple sclerosis prognostic value unclear systematic review aimed determine relationship location lesions cerebellum brainstem prognosis multiple sclerosis systematic review searched comprehensively read articles related research topic chinese,0.0
low contrast visual evoked potentials early detection optic neuritis optic neuritis detection important early diagnosis management multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd however conventional highcontrast visual evoked potential vep used detection lacks sensitivity identifying presenting mild unremarkable visual disturbance common firstepisode therefore study aimed investigate whether change contrast check size improves sensitivity vep,0.0
gut microbial antigenic mimicry autoimmunity gut microbiota plays major role developmental biology homeostasis cells belonging adaptive innate arms immune system alterations composition known regulated genetic environmental factors can either promote suppress pathogenic processes underlying development various autoimmune diseases including inflammatory bowel disease multiple sclerosis systemic lupus erythematosus type 1 diabetes rheumatoid,0.0
changes brain neuroimmunology following injury disease nervous immune systems intimately related brain periphery changes one affect viceversa immune cells responsible sculpting pruning neuronal synapses play key roles neurodevelopment neurological disease pathology immune composition brain tightly regulated periphery bloodbrain barrier bbb whose maintenance driven significant extent extracellular matrix ecm,0.0
cellular senescence factor extracellular hmgb1 directly inhibits oligodendrocyte progenitor cell differentiation impairs cns remyelination hmgb1 highly conserved ubiquitous protein eukaryotic cells hmgb1 normally localized nucleus acts chromatin associated nonhistone binding protein contrast extracellular hmgb1 alarmin released stressed cells act danger associated molecular pattern damp recently determined progenitor cells multiple sclerosis patients exhibit cellular senescent phenotype release extracellular hmgb1 directly impaired,1.0
evaluation humoral cellular immune responses sarscov2 vaccine patients common variable immunodeficiency phenotype patient receiving bcell depletion therapy conclusion effectiveness sarscov2 vaccines cvid phenotype bcd patients lower healthy individuals knowledge predictive factors humoral cellular response failure immunocompromised patients useful clinical practice thus studies regard clearly needed,0.0
microbial metabolites multiple sclerosis implications pathogenesis treatment metabolites produced gut microbiota shown play important role numerous inflammatory neuropsychiatric neurodegenerative diseases specifically microbial metabolites implicated modulation innate adaptive immunity especially generation regulatory t cells tregs key regulators multiple sclerosis ms pathogenesis furthermore affect processes relevant ms pathophysiology inflammation,0.0
working memory deficits multiple sclerosis overview findings although working memory wm information processing speed ips impairments multiple sclerosis ms widely investigated several questions regarding nature impairments relationship remain unclear aim short communication article present overview recent research findings regarding characteristics wm impairment ms patients precisely degree impairment observed wms component ie,0.0
spinal dural arteriovenous fistula mimic demyelinating disease radiculopathy spinal dural arteriovenous fistula sdavf characterized abnormal connection radicular artery venous plexus producing spinal cord venous congestion manifests nonspecific sensory motor symptoms present three cases sdavf different forms presentation two cases autoimmune etiology considered third case initial diagnosis chronic radiculopathy three cases serpentine enhancement observed,1.0
motor evoked potentials multiple sclerosis multiyear followup dataset multiple sclerosis ms chronic disease affecting millions people worldwide demyelinating axonal pathology ms signal conduction central nervous system affected evoked potential measurements allow clinicians monitor process can used decision support share dataset contains motor evoked potential mep measurements brain stimulated resulting signal measured hands feet results,1.0
preserved t cell responses sarscov2 anticd20 treated multiple sclerosis conclusions findings inform treatment decisions sarscov2 vaccination management pwms,0.0
teriflunomide normalizes antianxiety effect antianxa2 aps mice model teriflunomide antianxa2 mice model antiphospholipid syndrome aps affects brain hypercoagulation immunological mechanisms aps characterized several autoantibodies binding thrombolytic complex including beta2glycoprotein 2gpi annexin a2 anxa2 teriflunomide oral drug treatment multiple sclerosis ms cytostatic effect b cells therefore potential antibodytargeting treatment aps study assessed effect teriflunomide two aps mouse,0.0
role body fat multiple sclerosis susceptibility severity mendelian randomisation study conclusions findings provide evidence human genetics range features linked obesity important contributor ms development ms severity height nonfat mass importantly findings also identify potentially modifiable factor may reduce accumulation disability ameliorate ms severity,0.0
mapping risk infections patients multiple sclerosis multidatabase study united kingdom clinical practice research datalink gold aurum conclusion populationlevel elevated risk infection among pwms remained stable despite introduction diseasemodifying treatments,0.0
sarscov2 multiple sclerosis potential disease exacerbation respiratory tract primary route entry sarscov2 evidence shows virus also impacts central nervous system intriguingly case reports documented sarscov2 patients presenting demyelinating lesions brain spinal cord optic nerve suggesting possible implications neuroimmune disorders multiple sclerosis ms related neuroimmune disorders however cellular mechanisms underpinning observations remain poorly,1.0
biological markers early multiple sclerosis paved way radiologically isolated syndrome radiologically isolated syndrome ris characterized mritypical brain lesions fulfilling 2009 okuda criteria detected patients without clinical conditions suggestive ms half ris patients convert ms within 10 years individual course disease however highly variable 12 ris converting directly progressive ms demographic imaging markers associated risk clinical ms ris male sex younger age infratentorial,0.0
gut microbiota master puppets connecting epidemiology infectious autoimmune metabolic disease infectious autoimmune metabolic diseases put enormous pressure quality life economy three disease types known quality gut microbiota composition correlated onset progression disease hence maintaining eubiosis preventing gradual irreversible loss beneficial microbes within gut microbial ecosystem utmost importance epidemiological trends disease types may serve proxies,0.0
case report exacerbation relapses following mrna covid19 vaccination multiple sclerosis case series conclusion patients seek medical attention experiencing acute neurological symptoms especially vaccination fast diagnostic procedures prompt treatment performed patients pharmacovigilance study warranted confirm causality,0.0
fatigue multiple sclerosis review exploratory therapeutic potential noninvasive brain stimulation fatigue commonly reported symptom patients multiple sclerosis ms worrisome frequent debilitating manifestation occur time course ms subtypes engender professional familial socioeconomic consequences severely compromise patients quality life clinically symptom exhibits motor cognitive psychosocial facets also important differentiate perceived,0.0
vitamin d sources physiological role biokinetics deficiency therapeutic use toxicity overview analytical methods detection vitamin d metabolites vitamin d wellknown role calcium homeostasis associated maintenance healthy bones increases efficiency intestinal absorption dietary calcium reduces calcium losses urine mobilizes calcium stored skeleton however vitamin d receptors present ubiquitously human body indeed vitamin d plethora noncalcemic functions contrast vitamins sufficient vitamin d can synthesized human skin however,0.0
anticgrp therapies migraine multiple sclerosis patients abstract,0.0
stick twist costeffectiveness siponimod compared continuing existing diseasemodifying therapies treatment active secondary progressive multiple sclerosis uk conclusions recognition active spms treatment phenotype siponimod offers costeffective clinically beneficial treatment approach compared continuation oral infused rrms dmts,0.0
sarscov2 infection patients neuroimmunological disorders tertiary referral centre north portugal abstractintroductionthe impact covid19 patients neuroimmunological disorders fully established evidence suggesting increased risk severe infection associated use immunosuppressors populationobjectiveto characterize sarscov2 infection patients followed neuroimmunology outpatient clinic tertiary centre north portugalmethodsretrospective analysis neuroimmunological patients pcrproven sarscov2 infection observational period 20 monthsresultsninetyone patients infected 681 female mean age 489167 years median disease duration 110 iqr 60190 years sixtyone patients 670 multiple sclerosis 50 relapsingremitting course 12 132 myasthenia gravis mg 6 66 autoimmune encephalitis 6 66 chronic inflammatory demyelinating polyneuropathy seventysix patients 835 taking diseasemodifying therapy 776 immunosuppressants including anticd20 12 132 patients mild covid19 846 3 cases 33 severe disease 7 cases 77 critical disease reported total 13 patients hospitalized 4 died patients severe critical disease significantly older patients milder forms 694210 versus 465144 years p001 mg also associated severe disease p002 association comorbidities use immunosuppressors including anticd20 covid19 severityconclusionsgreater age mg associated severe critical covid19 found association specific dmt including anticd20 outcome clinical recovery achieved 934,1.0
sarscov2 infection patients neuroimmunological disorders tertiary referral centre north portugal abstractintroductionthe impact covid19 patients neuroimmunological disorders fully established evidence suggesting increased risk severe infection associated use immunosuppressors populationobjectiveto characterize sarscov2 infection patients followed neuroimmunology outpatient clinic tertiary centre north portugalmethodsretrospective analysis neuroimmunological patients pcrproven sarscov2 infection observational period 20 monthsresultsninetyone patients infected 681 female mean age 489167 years median disease duration 110 iqr 60190 years sixtyone patients 670 multiple sclerosis 50 relapsingremitting course 12 132 myasthenia gravis mg 6 66 autoimmune encephalitis 6 66 chronic inflammatory demyelinating polyneuropathy seventysix patients 835 taking diseasemodifying therapy 776 immunosuppressants including anticd20 12 132 patients mild covid19 846 3 cases 33 severe disease 7 cases 77 critical disease reported total 13 patients hospitalized 4 died patients severe critical disease significantly older patients milder forms 694210 versus 465144 years p001 mg also associated severe disease p002 association comorbidities use immunosuppressors including anticd20 covid19 severityconclusionsgreater age mg associated severe critical covid19 found association specific dmt including anticd20 outcome clinical recovery achieved 934,1.0
realworld study relapsingremitting multiple sclerosis patients treated teriflunomide nordic countries qualityoflife efficacy safety adherence outcomes abstractbackground teriflunomide 14 mg aubagio oncedaily oral drug approved treatment relapsing forms multiple sclerosis ms efficacy safety teriflunomide thoroughly characterised across extensive clinical program interested studying performance drug respect qualityoflife qol outcomes persons ms realworld settingmethods terilife prospective open label noninterventional observational multicentre study enrolled 200 teriflunomidetreated patients three nordic countries primary outcome measure changes patientreported qol 24 months measured short form36 sf36 questionnaire secondary endpoints included clinical efficacy fatigue safety treatment satisfaction treatment satisfaction questionnaire medication version 14 tsqm14 treatment adherence health economic outcomes assessments made baseline 6monthly intervalsresults overall changes sf36 scores baseline last visit indicated stable qol treatment teriflunomide 24 months relapse activity decreased study compared prebaseline period p0001 patientreported disability increased marginally substantial change seen fatigue scores mean scores tsqm domains increased nominally though significantly month 6 month 24 convenience side effects tsqm domains recorded highest median scores indicating acceptability oral teriflunomide cohort reflected generally high treatment adherence decreased healthcare utilization study period differences seen treatmentnave previously treated patients likely reflecting different patient demographics disease status study entry along different treatment expectationsconclusion terilife offers reliable snapshot qol efficacy safety health economic outcomes persons relapsing ms treated teriflunomide routine clinical practice nordic countries consistent previous clinical trials realworld studies,0.0
sylvia lawry centre multiple sclerosis research slcmsr critical review facing 20 anniversary abstractthe slcmsr formed international multiple sclerosis trials research resource center identify clinical mri predictors course multiple sclerosis ms based large database natural history clinical trial data using elaborate validation concept several key findings published challenging established outcome parameters assessment ms disability ratings expanded disability status scale edss relapses mri endpoints sustained increase edss appeared invalid outcome 23 year clinical trials least patients relapsingremitting ms number gadoliniumenhancing lesions t2lesion load mri shown meaningful additional predictive value disease course issues risen 15 years ago triggered controversial discussions also noticed regulatory authorities resolved addition slcmsr contributed development new outcomes realworld walking speed attractive ecologically valid tool based wearable device socalled evidencebaseddecisionsupport tool constructed provide individual prognostic estimates based matching algorithm given database paper condensates findings 20 years critical ms research,0.0
sylvia lawry centre multiple sclerosis research slcmsr critical review facing 20 anniversary abstractthe slcmsr formed international multiple sclerosis trials research resource center identify clinical mri predictors course multiple sclerosis ms based large database natural history clinical trial data using elaborate validation concept several key findings published challenging established outcome parameters assessment ms disability ratings expanded disability status scale edss relapses mri endpoints sustained increase edss appeared invalid outcome 23 year clinical trials least patients relapsingremitting ms number gadoliniumenhancing lesions t2lesion load mri shown meaningful additional predictive value disease course issues risen 15 years ago triggered controversial discussions also noticed regulatory authorities resolved addition slcmsr contributed development new outcomes realworld walking speed attractive ecologically valid tool based wearable device socalled evidencebaseddecisionsupport tool constructed provide individual prognostic estimates based matching algorithm given database paper condensates findings 20 years critical ms research,0.0
clinical outcomes partial sensory root rhizotomy patients recurrence multiple sclerosing trigeminal neuralgia percutaneous balloon compression abstractobjectiveto investigate clinical outcomes partial sensory root rhizotomy psr patients recurrence multiple sclerosing trigeminal neuralgia tnms percutaneous balloon compression pbc methods21 patients recurrence tnms pbc treated psr january 2012 july 2018 visual analogue score vas participants pbc psr observed postoperative recurrence rate pbc psr recorded postoperative complications also followed upresultsthe vas score reducing 03 points treatment defined effective 4 points invalid recurrence effective rates psr 1 day 6 months 12 months 18 months operation 100 100 95 81 respectively vas scores participants pbc psr significantly lower pbc psr p005 vas scores 1 day 6 months 12 months 18 months psr lower pbc p005 postoperative recurrence rates 6 months 12 months 18 months psr significantly lower pbc p005 psr 21 patients facial sensation loss one patient intracranial infection none occurred decrease masticatory muscle strength weakened corneal reflex intracranial hemorrhage facial paralysis cerebrospinal fluid leakageconclusionpsr lower pain recurrence rate significant reduction vas score compared pbc recommended treat patients recurrence tnms pbc,0.0
exgaussian analysis simple response time measure information processing speed relationship brain morphometry multiple sclerosis abstractbackgroundthe polyfactorial nature widely used symbol digit modalities test introduces significant measurement challenges characterizing information processing speed ips deficits multiple sclerosis ms measures high psychometric ipsspecificity less contamination cognitive domains necessary fully understand ips changesobjectiveinvestigate three mathematical modelling exgaussian parameter estimates mu sigma tau derived simple response time rt task 1 differentiate ms healthy control participants 2 correspond structural brain changes evaluate novel ips measurement approachmethodspersons without ms completed twominute behavioral simple rt task structural mri ms functional composite rt distributions deconvolved exgaussian parameter estimates using mathematical modelling group differences brainbehavior relationships statistically evaluatedresultspersons ms experienced general pattern slowing evidenced shift gaussian mu component distribution correlated whole brain volume white matter specifically additionally persons ms larger values tau elongated positively skewed tail may reflect attentional lapsesconclusionthe exgaussian approach sensitive diseaserelated ips changes provides nuanced information ips slowing ms,0.0
effects longterm hybrid assistive limb use gait patients amyotrophic lateral sclerosis objective assess longterm effects hybrid assistive limb hal treatment gait patients amyotrophic lateral sclerosis als methods three courses treatment hal administered three women als course four fiveweek duration treatment performed nine times rest period least two months course gait ability 2minuteswalk 10mwalk tests als functional rating scalerevised respiratory,0.0
myelinated axons primary target heminmediated oxidative damage model central nervous system iron released oligodendrocytes demyelination derived haemoglobin breakdown products believed amplify oxidative tissue injury multiple sclerosis ms however pathophysiological significance ironcontaining haemoglobin breakdown products rarely considered context ms cellular specificity mode action remain unclear using myelinating cell cultures now report cytotoxic potential hemin ferriprotoporphyrin ix,1.0
timed 25foot walk sensitive outcome measure edss ppms trials analysis promise clinical trial dataset conclusion investigation suggests t25fw may useful primary outcome measure edss ppms trials use may shorten clinical trials findings impact cels baseline disability outcomes inform critical appraisal clinical trials ppms,0.0
dimethyl fumarate review preclinical efficacy models neurodegenerative diseases dimethyl fumarate dmf antioxidative antiinflammatory drug approved treatment multiple sclerosis psoriasis however beneficial effects dmf also found inflammatory diseases cancers dmf prodrug immediately hydrolysed monomethyl fumarate mmf vivo fumarates activate nuclear factor erythroidderived 2 like 2 nrf2 pathway nrf2 key transcription factor antioxidant response immunosuppressive,0.0
lower basal metabolic rate associated increased risk osteosarcopenia postmenopausal women conclusions data suggest low bmr might early predictor concordance osteoporosis sarcopenia postmenopausal women,0.0
glatiramer acetate immunomodulation evidence neuroprotection cognitive preservation novel neuroprotective uses copaxone generic name glatiramer acetatega examined primarily neurological conditions involving cognitive decline ga wellstudied synthetic copolymer fdaapproved immunebased treatment relapsing remitting multiple sclerosis rrms clinical studies explored potential mechanism action moa outcomes ga immunization patients furthermore results animal studies suggest ga direct,1.0
synthesis evaluation serinolamide derivatives sphingosine1phosphate1 s1psub1 sub receptor agonists sphingosine1phosphate1 s1p 1 receptor agonists wellknown drugs treating multiple sclerosis ms caused autoreactive lymphocytes attack myelin sheath therefore effective therapeutic strategy reduce lymphocytes blood inducing s1p 1 receptor internalization synthesized serinolamide natural product sea performed s1p 1 receptor internalization assay evaluate functionally antagonistic s1p 1 receptor agonist activity,1.0
rhoa signaling neurodegenerative diseases ras homolog gene family member rhoa small gtpase rho family involved regulating multiple signal transduction pathways influence diverse range cellular functions rhoa many downstream effector proteins highly expressed nervous system implying important role rhoa signaling neurons glial cells indeed emerging evidence points toward role aberrant rhoa signaling neurodegenerative diseases parkinsons disease,0.0
glycoprotein nonmetastatic melanoma protein b gnmpb novel biomarker cerebral adrenoleukodystrophy adrenoleukodystrophy ald xlinked peroxisomal disease caused mutation abcd1 gene producing mutations long chain fatty acid transporter ald protein cerebral ald cald severe phenotype ald neuroinflammation neurodegeneration elevated levels glycoprotein nonmetastatic melanoma protein b gnmpb recently documented neurodegenerative diseases alzheimers disease multiple sclerosis amyotrophic lateral sclerosis,0.0
complex nlinked glycosylation potential modifier niemannpick disease type c1 pathology complex asparaginelinked glycosylation plays key roles cellular functions including cellular signaling protein stability immune response previously characterized appearance complex asparaginelinked glycosylated form lysosomeassociated membrane protein 1 lamp1 cerebellum npc1 mice lamp1 form found activated microglia appearance correlated spatially temporally cerebellar purkinje neuron loss test importance,0.0
endothelial ets1 inhibition exacerbate bloodbrain barrier dysfunction multiple sclerosis inducing endothelialtomesenchymal transition bloodbrain barrier bbb dysfunction recognized early pathological feature contributing factor multiple sclerosis endothelialtomesenchymal transition process associated endothelial dysfunction leading disruption vessel stability barrier function yet functional consequence multiple sclerosis remains unclear demonstrated endothelialtomesenchymal transition accompanied bloodbrain barrier dysfunction several,0.0
microrna alteration application biomarkers therapeutic approaches neurodegenerative diseases micrornas mirnas essential posttranscriptional gene regulators involved various neuronal nonneuronal cell functions play key role pathological conditions numerous studies demonstrated mirnas dysregulated major neurodegenerative diseases alzheimers disease parkinsons disease multiple sclerosis amyotrophic lateral sclerosis huntingtons disease hence present work constructed comprehensive overview individual microrna,0.0
exploring prophagocytic antiinflammatory functions pacap vip microglia implications multiple sclerosis multiple sclerosis ms chronic neuroinflammatory demyelinating disease central nervous system cns characterised infiltration peripheral immune cells multifocal whitematter lesions neurodegeneration recent years microglia emerged key contributors ms pathology acting scavengers toxic myelin cell debris modulating inflammatory microenvironment promote myelin repair review explore role two neuropeptides,1.0
proteomics multiple sclerosis perspective clinician multiple sclerosis ms inflammatory demyelinating neurodegenerative disease central nervous system cns affects approximately 28 million people worldwide last decade new era heralded new phenotypic classification new diagnostic protocol first ever therapeutic guideline making personalized medicine aim ms management however despite great evolution still many aspects disease unknown need,1.0
mir1505p let7b5p blood myeloid extracellular vesicles track cognitive symptoms patients multiple sclerosis cognitive deficits strongly affect quality life patients multiple sclerosis ms however cognitive ms biomarkers currently available extracellular vesicles evs contain markers parental cells able pass brain blood representing source disease biomarkers aim study investigate whether small noncoding micrornas mirnas targeting synaptic genes packaged plasma evs may reflect cognitive deficits ms patients,0.0
vitamin d fortification milk increase vitamin d intakes australian population comprehensive strategy required low vitamin d status serum 25hydroxyvitamin d 25 oh d concentration 50 nmol l prevalent australia ranging 15 32 adolescent adult populations vitamin d intakes also low across population recently estimated 1832 g day average assuming equal bioactivity d vitamers combination findings strongly suggest datadriven nutrition policy needed increase vitamin d intake improve status australian,0.0
methodological investigation time perspective scoring quality life among individuals multiple sclerosis achieving maintaining high quality life following diagnosis chronic illness positive impact experience illness including delayed disease progression fewer relapses time perspective shown promising relationships quality life though studies using construct samples chronic illness sparse methodologically heterogeneous participants n 123 diagnosed relapsingremitting multiple sclerosis least five years prior,0.0
big five personality traits positive orientation polish adults multiple sclerosis role meaning life scientific achievements concerning direct relation personality traits positive orientation among patients multiple sclerosis explain role potential mediators fact researchers argue traitspositivity association much complex seems reason made attempt analyze indirect relationship abovementioned variables including meaning life mediator total 618 patients ms took part,0.0
vitamin d pregnancy effect neonates children worldwide high prevalence vitamin d vd deficiency become growing concern potential adverse effects human health including pregnant women offsprings beyond classical function regulator calcium phosphate metabolism together fundamental role bone health every stage life deficiency associated multiple adverse health effects classic effects vd deficiency pregnancy neonates late,0.0
dietary patterns metabolic disorders polish adults multiple sclerosis diet plays major role aetiopathogenesis many neurological diseases may exacerbate symptoms inducing occurrence metabolic disorders results research role diet course multiple sclerosis ms ambiguous still consensus concerning dietary recommendations patients ms aim study analyse dietary patterns dps patients ms assess relationships dps,0.0
impact resistance training program static balance multiple sclerosis population randomized controlled trial study conclusions resistance training concentric phase maximum velocity showed impact balance sample future studies examine programs longer duration combined types training balance training aim obtaining improvements variable people ms,0.0
seroprevalence sarscov2 cohort patients multiple sclerosis diseasemodifying therapies conclusions according data pwms present higher risk covid19 infection compared results obtained general population evidence worse covid19 outcome pwms dmts significantly change frequency covid19 except interferon however findings must interpreted caution given small sample pwms taking dmt,0.0
development application fast ultrahigh performance liquid chromatographytrapped ion mobility mass spectrometry method untargeted lipidomics alteration lipid profile biological specimens plasma mirrors abnormalities homeostasis offers pivotal information disease comprehension fast analytical methods needed highlight changes plasma lipid profile deliver rapid results study developed fast reversed phase ultra high performance liquid chromatographytrapped ion mobility mass spectrometry rpuhplctimsms method untargeted lipidomics short narrowbore fully porous,0.0
case autoimmune glial fibrillary acidic protein astrocytopathy presenting magnetic resonance imaging mimics multiple sclerosis autoimmune glial fibrillary acidic protein gfap astrocytopathy inflammatory disorder central nervous system magnetic resonance imaging neuroradiological signature linear radial enhancement pattern cerebral white matter mri dawsons fingers hand ovoid lesions openring enhancement long recognized distinct features multiple sclerosis ms herein report case autoimmune gfap astrocytopathy presenting mri,0.0
devicemeasured physical activity sedentary behavior differ depression symptom status persons multiple sclerosis abstractbackgrounddepression highly prevalent impactful persons multiple sclerosis ms data indicating volume physical activity behavior differs depression symptom status ms yet less known volume sedentary behavior relationship depression know little physical activity patterns sedentary behavior depression msobjectivesthis study examined differences volume ie minutes day pattern ie bouts day bout length devicemeasured sedentary behavior physical activity function depression symptom status persons msmethodsthe sample adults ms n441 completed hospital anxiety depression scale hads wore waistmounted actigraph gt3x+ accelerometer waking hours 7 days participants divided subgroups elevated n127 nonelevated n314 depression symptoms based cutpoint hads scores ie 8+ indicative elevated depressive symptoms examined effect depression group status differences volume pattern sedentary behavior light lpa moderatetovigorous mvpa physical activity subgroups using multivariate analyses variance manova multivariate analysis covariance mancova controlling demographic clinical variables differed elevated nonelevated depression groupsresultsresults manova indicated overall difference subgroups volume pattern physical activity sedentary behavior nonelevated depression group significantly greater amount steps day mean m 45843 standard deviation sd 28213 elevated depression group m 37296 sd 25763 f87 p003 results mancova revealed statistically significant difference elevated nonelevated depression groups measures volume physical activity difference steps day became nonsignificant f 1 438 213 p146 controlling disability age disease duration educations yearsconclusionsthis study observed differences sedentary behavior physical activity function depression symptom status persons ms yet difference steps day initially results demonstrated disability age disease duration years education included mancova difference depression groups longer significant suggests steps day important target health promotion interventions among persons ms higher disability elevated depression symptoms,0.0
delayed recurrent dimethyl fumarate inducedlymphopenia patients multiple sclerosis abstractbackgroundearly lymphopenia known side effect dimethyl fumarate diseasemodifying therapy ms however longterm effects immune response impact lymphocyte counts another diseasemodifying treatment introduced remain unknown better understand specific aspects reviewed cases develop prolonged grade 2 4 lymphopenia dimethyl fumarate lausanne ms clinicmethodretrospective analysis 12 patients 101 discontinued dimethyl fumarate prolonged lymphopenia amongst 119 patients treated dimethyl fumarate reviewed demographics well clinical biological mri characteristics compared nonlymphopenic patients dimethyl fumarate therapy within timeframe 18 months switching another diseasemodifying treatment also focused lymphocyte subsets subgroup patientsresultscompared nonlymphopenic patients lymphopenic patients older dimethyl fumarate initiation 514 yo vs 397 p00003 majority male p0037 three 25 developed delayed lymphopenia one year treatment onset despite persistent lymphopenia three patients experienced disease activity amongst nine patients 75 switched another therapy five 556 presented recurrent lymphopenia predominantly cd8+ t cell decreaseconclusionsdimethyl fumarate longterm impact lymphocyte biology even discontinuation sustained reduction cd8+ t cells may increase opportunistic infection risk taken consideration switching therapies dimethyl fumarate,0.0
prevalence incidence season distribution mog antibodyassociated disease province verona italy abstractbackground myelin oligodendrocyte glycoprotein mog antibodyassociated disease mogad demyelinating disorder central nervous system whose epidemiological features still unclear report current prevalence incidence rates mogad population verona province italy seasonal distribution disease onsetmethods mogad patients residing verona province included consultation database neuropathology laboratory provincial prevalence determined 2021 1 1 resident population 922291 people incidence rates 2016 1 1 2021 1 1 calculated cases divided total number personyears risk also examined distribution attacks month seasonresults included 23 prevalent mogad cases 13 females median age onset 36 years range 569 prevalence rate 25 100000 95 ci 1737 22 incident cases collected incidence rate 48 million personyears 95 ci 3172 among 23 prevalent patients disease onset frequent december 4 cases february may september 3 cases month global autumnwinter predominance septemberfebruary 15 cases 65 irrespective clinical manifestationconclusions first study italian population report mogad prevalence incidence rates higher estimates aquaporin4seropositive neuromyelitis optica spectrum disorder caucasian population far lower multiple sclerosis autumnwinter predominance disease onset suggested related environmental factors ascertained although validation larger cohorts mandatory,1.0
delayed recurrent dimethyl fumarate inducedlymphopenia patients multiple sclerosis abstractbackgroundearly lymphopenia known side effect dimethyl fumarate diseasemodifying therapy ms however longterm effects immune response impact lymphocyte counts another diseasemodifying treatment introduced remain unknown better understand specific aspects reviewed cases develop prolonged grade 2 4 lymphopenia dimethyl fumarate lausanne ms clinicmethodretrospective analysis 12 patients 101 discontinued dimethyl fumarate prolonged lymphopenia amongst 119 patients treated dimethyl fumarate reviewed demographics well clinical biological mri characteristics compared nonlymphopenic patients dimethyl fumarate therapy within timeframe 18 months switching another diseasemodifying treatment also focused lymphocyte subsets subgroup patientsresultscompared nonlymphopenic patients lymphopenic patients older dimethyl fumarate initiation 514 yo vs 397 p 00003 majority male p 0037 three 25 developed delayed lymphopenia one year treatment onset despite persistent lymphopenia three patients experienced disease activity amongst nine patients 75 switched another therapy five 556 presented recurrent lymphopenia predominantly cd8+ t cell decreaseconclusionsdimethyl fumarate longterm impact lymphocyte biology even discontinuation sustained reduction cd8+ t cells may increase opportunistic infection risk taken consideration switching therapies dimethyl fumarate,0.0
defining milestones study remyelination using cuprizone mouse model early early abstractbackground cuprizone cpz copper chelator used produce reversible oligodendrocytopathy animals similarities pathology found human multiple sclerosis ms model attractive study remyelinationaims demonstrate twoweek period cessation cpz exposure sufficient establish changes compatible remyelination without accompanying behaviour brain magnetic resonance imaging mri disturbancesmethods two groups male c57bl 6 mice fed oral solution cpz 02 5 weeks w5 half animals kept vehicle another 2 weeks w7 5 7 weeks animals subjected battery behavioural tests 18 animals brain mri animals cerebellar samples studied gene expression protein levels gfap myelin proteolipid protein plp tnf il1results differences observed cpzexposed control animals regarding behaviour mri w5 w7 however myelin plp levels decreased cpz w5 treated animals changes reverted w7 gfap levels varied opposite directionconclusions observed changes validate use w5 w7 temporal moments study demyelination early remyelination model,1.0
defining milestones study remyelination using cuprizone mouse model early early abstractbackgroundcuprizone cpz copper chelator used produce reversible oligodendrocytopathy animals similarities pathology found human multiple sclerosis ms model attractive study remyelinationaimsto demonstrate twoweek period cessation cpz exposure sufficient establish changes compatible remyelination without accompanying behavior brain magnetic resonance imaging mri disturbancesmethodstwo groups male c57bl 6 mice fed oral solution cpz 02 5 weeks w5 half animals kept vehicle another 2 weeks w7 5 7 weeks animals subjected battery behavioural tests 18 animals brain mri animals cerebellar samples studied gene expression protein levels gfap myelin proteolipid protein plp tnf il1resultsno differences observed cpzexposed control animals regarding behavior mri w5 w7 however myelin plp levels decreased cpz w5 treated animals changes reverted w7 gfap levels varied opposite directionconclusionsobserved changes validate use w5 w7 temporal moments study demyelination early remyelination model,1.0
neuroimmunomodulatory balance pro antiinflammatory cytokines regulate mcov induced alteration gap junction protein cx43 mouse hepatitis virus mhv murine cov experimental model used understand viralinduced acute neuroinflammation chronic progressive demyelination characteristic hallmarks human neurological disease multiple sclerosis mhv induced neuroinflammation provides excellent causeeffective platform understand virus can initiate neuroinflammation causing direct neuroglial cell dystrophy leading chronic progressive myelin damage,1.0
micrornas t lymphocyte regulators multiple sclerosis microrna mirna class endogenous noncoding small rna regulatory activities generally regulates expression target genes posttranscriptional level multiple sclerosis ms thought autoimmunemediated chronic inflammatory demyelinating disease central nervous system cns typically affect young adults t lymphocytes play important role pathogenesis ms studies suggested mirnas involved regulating,1.0
multiple pathways fig4 contributions cellular homeostasis yeast mutations lipid phosphatase fig4 associated multiple neurodegenerative diseases including rare severe form charcotmarietooth disease known type 4j cmt4j cmt4j attributed dysregulation production turnover fig4s lipid substrate phosphoinositide signaling lipid pi3 5p2 disruption well characterized protein complex fab1vac14fig4 complex fig4 known play roles cell independent catalytic,0.0
two years covid19 ms community learnt far abstract,0.0
potential role bay117082 nfb blocker inhibiting experimental autoimmune encephalomyelitis c57bl 6j mice via declining nlrp3 inflammasomes multiple sclerosis ms inflammatory autoimmune demyelinating disease central nervous system nodlike receptor pyrin domaincontaining 3 nlrp3 inflammasome implicated pathogenesis ms animal model experimental autoimmune encephalomyelitis eae however exact mechanism nlrp3 inflammasome involved development ms eae clear nfkappab nfb associated activity nlrp3 inflammasomes role nfb,1.0
antimicrobial triclosan tcs increases production interleukin 1 beta il1 human immune cells triclosan tcs antimicrobial compound widely used personal hygiene products mouthwash toothpaste tcs can ingested absorbed skin found human blood breast milk urine interleukin1 beta il1 important proinflammatory cytokine produced immune cells monocytes lymphocytes plays critical role immune response regulation tissue repair cellular growth overproduction il1 can contribute,0.0
seroconversion following covid19 vaccination can optimize protective response cd20treated individuals although everincreasing number diseasemodifying treatments relapsing multiple sclerosis ms appear influence coronavirus disease 2019 covid19 severity concern use anticd20depleting monoclonal antibodies due apparent increased risk severe disease following severe acute respiratory syndrome corona virus two sarscov2 infection inhibition protective anticovid19 vaccine responses antibodies given,0.0
role g5 r7rgs complex regulation pain transmission sensory ganglia neuropathic pain chronic disorder resulting damage afferent nerve fibers central pain pathways often complication pathological conditions diabetes shingles multiple sclerosis stroke opioid epidemic elucidated need efficacious treatments neuropathic pain 2019 alone nearly 16 million people diagnosed opioid use disorder 48 000 people died synthetic opioid overdose despite addictive,0.0
spontaneous cardiovagal baroreflex sensitivity females multiple sclerosis multiple sclerosis ms progressive demyelinating disease central nervous system known disrupt autonomic function females ms increased risk cardiovascular disease partly due altered autonomic regulation arterial blood pressure longitudinal data suggest low spontaneous cardiovagal baroreflex sensitivity predictor cardiovascular disease therefore purpose investigation test hypothesis spontaneous cardiovagal,1.0
healthrelated quality life diroximel fumarate patients relapsing forms multiple sclerosis findings qualitative research using patient interviews conclusion patient perspective key aspect considering diseasemodifying therapy ms given multitude options currently available overall wellness ease administration minimal manageable side effects drfrelated concepts meaningful patients therapy acknowledging patient perceptions shared decisionmaking may lead greater patient adherence optimal treatment outcomes,0.0
characterization structural features driving promiscuous ligand binding gmcsf granulocyte macrophage colony stimulating factor gmcsf cytokine involved myelopoiesis well immunomodulation gmcsf shown worsen conditions rheumatoid arthritis ra multiple sclerosis ms ameliorating diseases type diabetes gmcsf also used clinically combat neutropenia based immunostimulatory activity pathophysiological properties gmcsf highlighted incidence global pandemic covid19,0.0
longterm trajectories employment status workhours disability support pension status first episode cns demyelination conclusion trajectories indicate substantial heterogeneity complex impact ms employment earliest timepoints understanding trends enable better targeting interventions facilitate workforce retention particularly females higher number comorbidities frequent relapses greater rate disability accrual,1.0
ethanol inhibits metabolism multiple sclerosis drug dimethyl fumarate active metabolite decreases brain exposure conclusions ethanol inhibits hydrolysis dimethyl fumarate active monomethyl fumarate carboxylesterase 1 drastic effect disposition dimethyl fumarate monomethyl fumarate therapeutic effect dimethyl fumarate likely significantly altered consumption ethanol drug inhibits carboxylesterase 1 potentially altering beneficial effect chronic dimethyl fumarate therapy relapsingremitting multiple sclerosis,0.0
rare case balo concentric sclerosis subtype tumefactive multiple sclerosis 40yearold male case report balo concentric sclerosis bcs rare subvariant multiple sclerosis ms demyelinating disease affecting cns bcs considered disease brains white matter characteristic tumefactive ring signified alternating myelinated demyelinated layers gives onionring appearance patient 40yearold male past medical history pmh human papillomavirus hpv presented hospital acute onset progressive horizontal,1.0
disparate abilities nrf2 activators protect various electrophilic oxidative insults electrophilic oxidative stress contribute major diseases cancer diabetes smallmolecule activators nrf2 cytoprotective pathway show significant promise prevention amelioration chronic diseases combating stressors upregulation detoxification antioxidant enzymes understudied area whether distinct small molecular nrf2 activators can protect cells electrophilic oxidative stressors whether certain molecules,0.0
mechanistic insights sulfonamidebased nlrp3 inhibitors treatment neurodegenerative diseases neuroinflammation proven play important role pathogenesis neurodegenerative diseases encouraging expression maturation proinflammatory regulators studies shown upregulation proinflammatory cytokines interleukin il 1 il18 neurodegenerative diseases including alzheimers disease ad parkinsons disease pd multiple sclerosis ms traumatic brain injury tbi many nlrp3 nod lrr pyrin domaincontaining protein 3,0.0
integrating lipidomics transcriptomics reveals crosstalk oxidative stress neuroinflammation central nervous system demyelination multiple sclerosis ms incurable progressive neurodegenerative disease affects 25 million people worldwide brings tremendous economic pressures society however pathophysiology ms still fully elucidated effective treatment demyelination thought primary pathophysiological alteration ms previous study found abnormal lipid metabolism demyelinated corpus callosum growing evidence indicates,1.0
effect honey bee venom experimental autoimmune encephalomyelitis eae model multiple sclerosis ms experimental autoimmune encephalomyelitis eae widely employed model study multiple sclerosis ms interleukin27 il27 inhibits th17 activity breaks normal activity effector t cells cause autoimmunity bee venom bv used form medicine time ancient greece china bv bvderived active components might potent therapeutic effects refractory immunological neurodegenerative diseases ms study aimed,0.0
acute multiple sclerosis exacerbation vaccination johnson amp johnson covid19 vaccine novel presentation first documented case report multiple sclerosis ms neurologic disease caused chronic autoimmune process resulting demyelination axons within central nervous system ms occurs combined genetic susceptibility environmental triggers ms relapses msr characterized acute inflammatory reactions symptoms present novel case msr following second dose johnson johnson coronavirus disease 2019 covid19 vaccine johnson johnson new brunswick new jersey,1.0
integrative therapies amyotrophic lateral sclerosis disease using dynamic physiological systems conclusion study identify smoking physical activity environmental exposure occupational factors dietary habits risk factors protective factors onset progression als als multiple pathological mechanisms since integrative therapy contains various components display multiple effects helpful alleviating pathological events affecting patients als thereby increasing quality life individuals families,0.0
superinfection obstructive appendiceal mucocele case report appendiceal mucocele uncommon entity may arise due benign malignant processes radiologic exploration entity necessary diagnosis imaging manifestations vary findings common others specifically radiological findings superinfected mucocele rare reports literature herein present case 68yearold male patient superinfected appendiceal obstructive mucocele caused,0.0
periodic plasmapheresis maintenance treatment relapsingremitting multiple sclerosis new therapeutic line case report conclusion although specific studies needed case provides information potential new maintenance treatment patients relapsingremitting multiple sclerosis refractory diseasemodifying drug therapies,0.0
building distributed research network undergraduate opportunities molecular biochemistry covid19 pandemic brought light continued issues access research opportunities many undergraduate students researchintensive institutes lost ability go labs gain experience however students smaller colleges universities faced challenges bring research opportunities students long pandemic thus lowercost community colleges higher education institutes diverse students lack equity comes,0.0
defining dopaminemediated changes nlrp1 nlrc5 nlrc4 aim2 inflammasomes human myeloid cells although study dopamine often associated regulation reward motor function growing body research indicates dopamine also acts immunomodulatory regulator data show dopamine can influence secretion inflammatory cytokines myeloid cells macrophages microglia specifically shown dopamine modulates inflammation primary human monocytederived macrophages hmdm activation transcription factor,0.0
basal metabolic rate risk multiple sclerosis mendelian randomization study determine relationship basal metabolic rate bmr multiple sclerosis ms susceptibility analyzed genomewide association study gwas summary statistics data international multiple sclerosis genetics consortium total 115 803 participants european descent including 47 429 patients ms 68 374 controls selected 378 independent genetic variants strongly associated bmr gwas involving 454 874 participants instrumental variables,0.0
prioritization risk genes multiple sclerosis refined bayesian framework followed tissuespecificity cell type feature assessment conclusions summary predicted validated highconfidence ms risk gene set diverse genomic epigenomic eqtl singlecell drug data msprgenes serve benchmark ms gwas risk genes future validation genetic studies,0.0
multistep genomic approach prioritized tbkbp1 gene relevant multiple sclerosis susceptibility conclusions evidence novel signal association ms specific italian continental population found nevertheless two ms loci seems play relevant role raising interest investigations tbkbp1 gene,0.0
isolated sixth nerve palsy rare first presentation multiple sclerosis true isolated sixth nerve palsy initial presentation multiple sclerosis ms rare ms chronic inflammatory immunemediated disease central nervous system common cause neurological disability young adults common symptoms include acute episodes muscle weakness altered sensation balance gait disturbances visual loss bladder dysfunctiondiagnosis ms supported incidence symptomatic clinical episodes subsequent,0.0
myelodysplastic syndrome alemtuzumabtreated multiple sclerosis patient abstract,0.0
factors associated serological response sarscov2 vaccination patients multiple sclerosis treated rituximab conclusions relevance cohort study found optimal vaccine response tozinameran rituximabtreated patients multiple sclerosis may vaccinated soon possible rituximab treatment delayed bcell counts reached least 40 l additional vaccination tozinameran considered point,0.0
conservation divergence myelin proteome oligodendrocyte transcriptome profiles humans mice human myelin disorders commonly studied mouse models since clades evolutionarily diverged approximately 85 million years ago critical know extent myelin protein composition remained similar use quantitative proteomics analyze myelin purified human white matter find relative abundance structural myelin proteins plp mbp cnp septin8 correlates well c57bl 6n mice conversely multiple proteins,1.0
enhancement regnase1 expression stem looptargeting antisense oligonucleotides alleviates inflammatory diseases regnase1 ribonuclease plays essential roles restricting inflammation degrading messenger rnas mrnas involved immune reactions via recognition stemloop sl structures 3 untranslated regions 3utrs dysregulated expression regnase1 associated pathogenesis inflammatory autoimmune diseases mice humans developed therapeutic strategy suppress inflammatory responses blocking regnase1 selfregulation,0.0
inflammation multiple sclerosis induces specific reactive astrocyte state driving noncellautonomous neuronal damage abstract,0.0
ean brain health strategy one brain one life one approach conclusions adopting one brain one life one approach strategy cooperation partner societies international organisations policymakers significant number neurological disorders may prevented enhancing overall wellbeing individuals maintaining brain health life course,0.0
burden multiple sclerosis impact patient family society abstractbackgroundmultiple sclerosis ms chronic autoimmune neurological disease significantly influences healthrelated quality life individuals families societyaimthis study aimed identify burden ms patients caregivers quality life methodsa total 104 individuals included consisting 60 patients ms pwms diagnosed according revised mcdonald criteria 44 caregivers collecting detailed history participants complete general neurological examinations performed workrelated difficulties patients including physical cognitive psychological barriers studied using 23item multiple sclerosis work difficulties questionnaire mswdq23 caregivers asked complete caregiver strain index csi resultspwms higher disabilities higher statistically significant cognitive impairment workrelated difficulties addition csi significant positive correlation age pwms r048 p0001 disability illness r081 p0001 significant negative correlation cognitive affection r048 p0001 thereby indicating significant association burden caregivers workplace problems assessed mswdq23 score reported pwms r074 p001 conclusionas ms debilitating disease affecting psychological physical conditions patients well workrelated abilities significantly affects patients caregivers quality life,0.0
onset multiple sclerosis preventable time act now available,0.0
onset multiple sclerosis preventable time act now available,0.0
simulated attack reveals lesions affect network properties poststroke aphasia aphasia prevalent cognitive syndrome caused stroke rarity premorbid imaging heterogeneity lesion obscures links local effects lesion global anatomical network organization aphasia symptoms applied simulated attack approach humans examine effects 39 stroke lesions 16 females anatomical network topology simulating effects control sample 36 healthy 15 females brain networks focused measures global network organization thought support overall brain function resilience whole brain within left hemisphere removing lesion volume network topology measures behavioral scores western aphasia battery aphasia quotient wabaq four behavioral factor scores obtained neuropsychological battery factor sum compared behavioral variance accounted simulated poststroke connectomes observed randomly permuted data global measures anatomical network topology whole brain left hemisphere accounted 10 variance wabaq lexical factor score beyond lesion volume null permutations streamline networks provided reliable point estimates fa networks edge weights network efficiency weighted highly predicting wabaq fa networks overall results suggest global network measures provide modest statistical value beyond lesion volume predicting overall aphasia severity less value predicting specific behaviors variability estimates induced premorbid ability deafferentation diaschisis neuroplasticity following strokesignificance statementpoststroke remaining neuroanatomy maintains cognition supports recovery however studies often utilize small crosssectional samples fully model interactions lesions variables affect networks stroke alternate methods required account effects simulated attack models computational approaches apply virtual damage brain measure putative consequences using simulated attack model estimated simulated damage anatomical networks account language performance overall results reveal global network measures can provide modest statistical value predicting overall aphasia severity less value predicting specific behaviors findings suggest theoretically precise network models necessary robustly predict individual outcomes aphasia,0.0
burden multiple sclerosis impact patient family society abstractbackground multiple sclerosis ms chronic autoimmune neurological disease significantly influences healthrelated quality life individuals families societyaim study aimed identify burden ms patients caregivers quality life methods total 104 individuals included consisting 60 patients ms pwms diagnosed according revised mcdonald criteria 44 caregivers collecting detailed history participants complete general neurological examinations performed workrelated difficulties patients including physical cognitive psychological barriers studied using 23item multiple sclerosis work difficulties questionnaire mswdq23 caregivers asked complete caregiver strain index csi results pwms higher disabilities higher statistically significant cognitive impairment workrelated difficulties addition csi significant positive correlation age pwms r048 p0001 disability illness r081 p0001 significant negative correlation cognitive affection r048 p0001 thereby indicating significant association burden caregivers workplace problems assessed mswdq23 score reported pwms r074 p001 conclusion ms debilitating disease affecting psychological physical conditions patients well workrelated abilities significantly affects patients caregivers quality life,0.0
smarter adaptive platform clinical trials neurology showcase uk innovation abstract,0.0
singlecell profiling reveals periventricular cd56supbright sup nk cell accumulation multiple sclerosis multiple sclerosis ms chronic demyelinating disease characterised immune cell infiltration resulting lesions preferentially affect periventricular areas brain despite research efforts define role various immune cells ms pathogenesis focus immune cell populations fullspectrum analysis encompassing others natural killer nk cells performed used singlecell mass cytometry cytof profile,1.0
aquaporin4 prevents exaggerated astrocytosis structural damage retinal inflammation aquaporin4 aqp4 molecular target immune response neuromyelitis optica nmo leads severe structural damage central nervous system cns retina conversely aqp4 might upregulated astrocytes compensatory event multiple sclerosis thus functional relevance aqp4 neuroinflammation needs defined tested role aqp4 retina mog 3555 induced experimental autoimmune encephalomyelitis eae using optical,0.0
micrornas oligodendrocyte development remyelination oligodendrocytes glial cells responsible formation myelin around axons central nervous system cns myelin insulating layer allows electrical impulses transmit quickly efficiently along neurons myelin damaged chronic demyelinating disorders multiple sclerosis ms impulses slow remyelination oligodendrocytes often ineffective ms part failure oligodendrocyte precursor cells opcs,1.0
agedependent grey matter demyelination associated leptomeningeal neutrophil accumulation people living multiple sclerosis ms experience episodic central nervous system cns white matter lesions instigated autoreactive t cells age ms patients show evidence grey matter demyelination experience devastating nonremitting symptomology drives progression unclear hampered lack suitable animal models show passive experimental autoimmune encephalomyelitis eae induced adoptive transfer young th17 cells induces,1.0
syncytin1 nonfusogenic activities modulate inflammation contribute preeclampsia pathogenesis maternal cellular humoral immune responses allogeneic fetoplacental unit normal part pregnancy adaptation overactive dysregulated immune responses often manifest inflammation considered key element development preeclampsia infiltration activation macrophages nature killer cells t lymphocytes frequently observed decidua placenta associated preeclampsia addition local inflammation systemic inflammatory,0.0
associations corpus callosum damage clinical disability surfacebased homologous interhemispheric connectivity multiple sclerosis axonal damage corpus callosum prevalent multiple sclerosis ms although callosal damage associated disrupted functional connectivity hemispheres unclear relates cognitive physical disability investigated phenomenon using advanced measures microstructural integrity corpus callosum surfacebased homologous interhemispheric connectivity shic cortex found shic significantly decreased primary motor,0.0
multidisciplinary neurocutaneous syndrome clinics systematic review institutional experience conclusions best authors knowledge first detailed description comprehensive pediatric neurocutaneous clinic us serves patients multiple syndromes currently heterogeneity described multidisciplinary clinic structures practices detailed accounts clinic compositions practices along patient data outcomes needed order establish comprehensive efficient multidisciplinary approach,0.0
effect electrode montage 500hz tone burst evoked masseter vestibular evoked myogenic potential conclusions study revealed significant difference p11 n21 latencies well p11n21 rectified amplitude zygomatic mandibular montage using 500hz tone burst stimulus young adults hence utilizing 500hz tone burst mvemp can recorded zygomatic mandibular electrode montage,0.0
neuroprotection neuroregeneration roles white matter efficient strategies neuroprotection repair still unmet medical need neurodegenerative diseases lesions central nervous system last decades great deal attention focused white matter potential therapeutic target mainly due discovery oligodendrocyte precursor cells adult central nervous system cell type able fully repair myelin damage development advanced imaging techniques visualize,1.0
exploring steroid tapering patients neuromyelitis optica spectrum disorder treated satralizumab sakurasky case series abstract,0.0
guilty association epsteinbarr virus multiple sclerosis abstract,0.0
link neuropathic pain constipation nmosd mogad results online patient survey possible clinical implications conclusions np constipation seen majority nmosd mogad patients history myelitis interestingly onethird patients symptoms reported link majority reporting np severity increased worse constipation possible association opens possibility new approach managing np tends poorly responsive symptomatic therapies associated worse quality life nmosd mogad,0.0
priming microglia type ii interferon lasting resistant modulation interleukin10 situ immunological priming type ii interferon ifn crucial evoking neurotoxic phenotypes microglia tissueresident macrophages report serial exposure hippocampal slice cultures ifn lipopolysaccharide tolllike receptor 4 ligand induces high release il6 tnf nitric oxide concomitant loss electrical network activity neuronal gamma oscillations neurodegeneration notably effects still present 3 days ifn removal,0.0
validity sensitivity canadian normative data minimal assessment cognitive function multiple sclerosis macfims battery abstractbackgroundcanada amongst countries highest rates multiple sclerosis ms given cognitive deficits can occur 70 individuals ms need canadian normative data allows clinicians researchers evaluate cognitive impairment discrete regressionbased canadian normative data minimal assessment cognitive function ms macfims recently published current study sought evaluate discriminant predictive ability norms canadian ms samplemethods188 individuals confirmed diagnosis ms 174 matched healthy controls completed macfims batteryresultsindividuals ms performed worse healthy controls macfims measures significant degree similarly greater frequency impairment also observed measure ms group defining global impairment 15 standard deviations mean least 2 tests macfims battery identified cognitive impairment 4149 canadian ms sample area curve analyses showed acceptable discriminatory ability measures difference sensitivity detecting cognitive impairment observed comparing discrete vs regressionbased canadian normsconclusionthe macfims able detect cognitive impairment canadian ms sample can discriminate individuals ms healthy controls using canadian norms validation norms will allow clinicians researchers evaluate cognitive impairment using culturallyappropriate comparisons canadians living ms,0.0
innovative animal monitoring device experimental autoimmune encephalomyelitis d eae detailed evaluation improved results abstractbackground experimental autoimmune encephalomyelitis eae widely used animal model multiple sclerosis ms rapid model commonly induced rodents even eae replicate ms characteristics appropriate investigate development disease including immune neuroinflammatory aspects besides eae also shown relevant model preclinical studies several drugs effective model beneficial ms patients however despite widespread use consensus clinical assessment animals researchers perform daily evaluation classify 5point scale many authors also use inbetween scores apply systems besides among 5point scale different score definitions used recapitulate signs symptoms animal can show thus based experience eae aim present work develop new scoring system methods designed d eae tool independently evaluates 9 different items innovative detailed scoring system yet simple nonexperts use new scale tested eaeinduced mice three experiments different evaluators assessed animals blindly results d eae scoring system highly correlates commonly used 5point scale importantly enables detailed evaluation conclusions considering high reproducibility interrater reliability d eae useful tool eae monitoring,0.0
longitudinal humoral response ms patients treated cladribine tablets receiving second third doses sarscov2 mrna vaccine abstractbackgroundmultiple sclerosis ms patients receive immunomodulatory treatments can influence ability maintain vaccine specific serological response overtime ms patients treated cladribine tablets developed positive serology response following two doses mrna covid19 vaccine however limited data regarding effect cladribine tablets longterm humoral response second third boostermethodsserology response sarscov2 tested healthy controls hcs ms patients treated cladribine tablets 6 912 months second dose 1 36 months following third boosterdose btn162b2 mrna vaccineresultsthirtyfive 36 ms patients treated cladribine tablets 100 46 46 hcs positive serology response 10 months second vaccine dose addition cladribine tablets treated ms patients 22 22 hcs 24 24 positive robust serology response following third vaccine positive humoral response sustain 6 months one month third vaccine dose igg levels significantly lower patients treated cladribine tablets compared hcs 15598+11313 vs 26394+11335 p001 sixmonth post second vaccine 36 months post third vaccine difference igg levels groups 1088010720 vs 115309971 p079 5234+4097 vs 11198+14679 p04 conclusion relevancems patients treated cladribine tablets sustained positive vaccine specific serology response following second third sarscov2 vaccine dose,0.0
innovative animal monitoring device experimental autoimmune encephalomyelitis d eae detailed evaluation improved results abstractbackground experimental autoimmune encephalomyelitis eae widely used animal model multiple sclerosis ms rapid model commonly induced rodents even eae replicate ms characteristics appropriate investigate development disease including immune neuroinflammatory aspects besides eae also shown relevant model preclinical studies several drugs effective model beneficial ms patients however despite widespread use consensus clinical assessment animals researchers perform daily evaluation classify 5point scale many authors also use inbetween scores apply systems besides among 5point scale different score definitions used recapitulate signs symptoms animal can show thus based experience eae aim present work develop new scoring system methods designed d eae tool independently evaluates 9 different items innovative detailed scoring system yet simple nonexperts use new scale tested eaeinduced mice three experiments different evaluators assessed animals blindly results d eae scoring system highly correlates commonly used 5point scale importantly enables detailed evaluation conclusions considering high reproducibility interrater reliability d eae useful tool eae monitoring,0.0
validity sensitivity canadian normative data minimal assessment cognitive function multiple sclerosis macfims battery abstractbackgroundcanada amongst countries highest rates multiple sclerosis ms given cognitive deficits can occur 70 individuals ms need canadian normative data allows clinicians researchers evaluate cognitive impairment discrete regressionbased canadian normative data minimal assessment cognitive function ms macfims recently published current study sought evaluate discriminant predictive ability norms canadian ms samplemethods188 individuals confirmed diagnosis ms 174 matched healthy controls completed macfims batteryresultsindividuals ms performed worse healthy controls macfims measures significant degree similarly greater frequency impairment also observed measure ms group defining global impairment 15 standard deviations mean least 2 tests macfims battery identified cognitive impairment 4149 canadian ms sample area curve analyses showed acceptable discriminatory ability measures difference sensitivity detecting cognitive impairment observed comparing discrete vs regressionbased canadian normsconclusionthe macfims able detect cognitive impairment canadian ms sample can discriminate individuals ms healthy controls using canadian norms validation norms will allow clinicians researchers evaluate cognitive impairment using culturallyappropriate comparisons canadians living ms,0.0
transplant tolerance clonal deletion quest understand allogeneic transplanted tissue rejected tolerance induced led fundamental concepts immunology first review research led clonal deletion theory late 1950s since dominated field immunology transplantation time many basic mechanisms immune response unknown including role lymphocytes t cells rejection original observations reassessed considering t,0.0
opercular syndrome rare presentation schilders variant multiple sclerosis abstract,0.0
researching covid19 progressive ms requires globally coordinated multidisciplinary multistakeholder approachperspectives international progressive ms alliance conclusion papers calls action represent path toward shared research agenda multistakeholder longterm investigations will required drive evolve agenda,0.0
fatigue cognition inflammatory biomarkers changes response computerbased cognitive training multiple sclerosis patients randomized controlled trial conclusion addition computerbased cognitive training rehabilitation program ms patients efficient improving disease course via decreasing fatigue levels enhancing cognitive abilities reducing level inflammatory biomarkers,0.0
nephrogenic systemic fibrosis osseous metaplasia kidneypancreas transplant patient french caucasian woman history nonobstructive hypertrophic cardiopathy type 1 diabetes mellitus cataract antehypophysary insufficiency undergone multiple magnetic resonance imaging mri studies developed endstage renal disease esrd undergone hemodialysis 10 years receiving kidneypancreas allotransplantation age 48 years received antithymocyte globulins induction immunosuppression steroids 5 mg d mycophenolate,0.0
agespecific effects childhood body mass index multiple sclerosis risk conclusion provide evidence using mr genetically determined higher bmi early life associated increased ms risk effect may driven shared genetic architecture laterlife bmi,0.0
sensitive convenient detection mirna145 using gold nanoparticlehcr coupled system computational vitro validations multiple sclerosis ms remains challenging disease requires timely diagnosis therefore ultrasensitive optical biosensor based hybridization chain reaction hcr developed detect microrna145 mirna145 ms biomarker construct sensor hcr occurred specific hairpin probes mb1 contains polycytosine nucleotide loop mb2 polyguanine nucleotide sticky end introducing mir145 target sequence longrange dsdna polymers formed,0.0
promising cognitive screener multiple sclerosis nih toolbox cognition battery concords gold standard neuropsychological measures conclusions nihtb concords goldstandard measures classifies cognitive impairment similar rates macfims adjusted nihtb fluid cognition negatively associated disease severity suggesting clinical utility psychometric validation nihtb clinical practice will elucidate promise cognitive screener ms,0.0
comparison follicular t helper cells monocytes t cells priming newly diagnosed rituximabtreated ms patients healthy controls conclusion implications data suggest following treatment rtx tfh cells monocytes t cells priming declined happened fewer t cells activated also due interaction b cells tfh cells tfh targeting assessed therapeutic strategy ms,0.0
multiple sclerosis genetic nongenetic factors interact transient transcriptome clinically actionable understanding multiple sclerosis ms etiology goes gwas interpretation prompting research new gene regulatory models previous investigations suggested heterogeneity etiology components stochasticity interaction genetic nongenetic factors find unifying model evidence focused recently mapped transient transcriptome tt mostly coded intergenic intronic regions halflife,0.0
role chitinase 3like 1 biomarker multiple sclerosis systematic review metaanalysis background objectives multiple sclerosis ms autoimmune disease confined cns course frequently subtle variable therefore predictive biomarkers needed scenario conducted systematic review metaanalysis evaluate reliability chitinase 3like 1 biomarker ms,0.0
bladder stone causing vesicovaginal fistula migration vagina bladder stone known complication neurogenic bladder can rarely cause vesicovaginal fistula vvf presenting case woman late 70s bed bound progressive multiple sclerosis ms referred urology consideration suprapubic catheter due difficulty managing indwelling urethral catheter ultrasonogram usg identified 47 cm bladder stone rightsided hydronephrosis hn left atrophic kidney ct scan later,0.0
impact gut microbiome extraintestinal autoimmune diseases prevalence autoimmune diseases ads worldwide rapidly increased past decades thus addition classical risk factors ads genetic polymorphisms infections smoking environmental triggers considered recent sequencingbased approaches revealed patients extraintestinal ads multiple sclerosis rheumatoid arthritis type 1 diabetes systemic lupus erythematosus distinct gut microbiota compositions compared,0.0
combined effects cerebellar tdcs taskoriented circuit training people multiple sclerosis pilot randomized control trial conclusions taskoriented training improves balance mobility people multiple sclerosis ctdcs boost motor training effects,0.0
deuterium metabolic imaging hyperpolarized sup13 supcmri normal human brain clinical field strength reveals differential cerebral metabolism deuterium metabolic imaging dmi hyperpolarized 13 cpyruvate mri 13 chpmri two emerging methods noninvasive nonionizing imaging tissue metabolism imaging cerebral metabolism potential applications cancer neurodegeneration multiple sclerosis traumatic brain injury stroke inborn errors metabolism directly compare two noninvasive methods 3 t first time humans show simultaneously probe oxidative,0.0
relationship processing speed verbal nonverbal new learning memory progressive multiple sclerosis conclusion results indicate little ability beyond chance predict cvltii sdmt 61 albeit statistically significant contrast 77 chance model distinguish impaired nonimpaired bvmtr several potential explanations discussed,0.0
benefits equineassisted therapies people multiple sclerosis systematic review systematic review aimed provide uptodate analysis effects equineassisted therapies eat people multiple sclerosis pwms preferred reporting items systematic reviews metaanalyses prisma guidelines followed conduct systematic review pubmed web science databases employed search ended february 2022 risk bias analysis performed using evidence project tool removing duplicates,0.0
eosinophilic fasciitis smoldering multiple myeloma exceptional association young adults eosinophilic fasciitis ef shulmans fasciitis rare condition characterized subcutaneous edematous induration sparing face distal extremities progressing skin sclerosis association pathologies notably hemopathies described literature association smoldering multiple myeloma remains rare especially younger subject,0.0
highvolume highintensity functional training patients multiple sclerosis pilot study feasibility functional capacity conclusion new highvolume highintensity functional training programme appeared feasible patients ms may improve functional capacity aerobic capacity muscle strength largescale controlled trial longer period time required evaluate added value training programme,0.0
ageassociated impairment t cell immunity linked sexdimorphic elevation nglycan branching impaired t cell immunity aging increases mortality infectious disease branching asparaginelinked glycans critical negative regulator t cell immunity show branching increases age females males nave memory t cells cd4 + cd8 + t cells female sex hormones thymic output nave t cells t n decrease age however neither thymectomy ovariectomy altered branching interleukin7 il7,0.0
effectiveness acceptance commitment therapy improving quality life mood individuals multiple sclerosis systematic review metaanalysis abstractobjective review evidence effectiveness acceptance commitment therapy act intervention quality life mood individuals multiple sclerosis ms method systematic search conducted psycinfo cinahl embase medline web science scopus contextualscienceorg 13 01 2022 grey literature also searched via proquest dissertations theses prospero included randomised controlled trials rcts published english examined effectiveness act people diagnosis ms interested outcomes quality life qol mood eg anxiety depression stress acttargeted processes methodological quality assessed using cochrane risk bias tool v2 available extracted data entered metaanalysis determine weighted effect size estimates outcomes interestresults six studies 191 participants 142 identified met inclusion criteria metaanalyses indicated statistically significant small effect stress smd049 95 ci 089 008 favour act statistically significant effects act anxiety smd 041 95 ci 093 011 depression smd092 95 ci 191 006 acttargeted processes smd018 95 ci 062 025 small nonsignificant effect qol favour control conditions smd039 95 ci 008 085 methodological quality studies variable one study least one high risk biasconclusions findings suggest small effect act reducing stress people ms reducing anxiety depression improving quality life due small sample sizes studies within area generalisability findings limited future trials pay attention methodological rigour,0.0
crosssectional analysis persistence diseasemodifying therapies treatment nave experienced patients relapsing multiple sclerosis healthsystem specialty pharmacy abstractbackgroundpatients relapsing multiple sclerosis rms maintained diseasemodifying therapy dmt prevent disease progression reported persistence rates dmts varied concerningly low limited data exists longterm persistence rates reasons dmt discontinuation patients rms study evaluated longterm dmt persistence rates reasons dmt discontinuation switch specialty pharmacist involvement dmt treatment transitions predictors associated nonpersistence treatment nave experienced patientsmethodswe performed singlecenter retrospective crosssectional review patients rms 3 fills dmt healthsystem specialty pharmacy mayoctober 2017 patients followed 3 years determine dmt persistence defined time patient remained index dmt descriptive statistics used summarize sample characteristics outcomes kaplanmeier estimation method used estimate probability remaining persistent used cox proportional hazards regression model analyze primary outcome rates reasons dmt discontinuation identified via pharmacy claims confirmed via chart review electronic health recordresultsthe study included 540 patients 41 76 treatment nave 3 years 193 36 patients remained index dmt probability remaining persistent 3 years 051 95 confidence interval ci 047056 median time index dmt 642 days interquartile range 3171096 347 patients continue index dmt 91 26 discontinued 136 39 switched new dmt 92 27 transferred care new specialty pharmacy provider 21 6 lost followup 7 2 died common reasons dmt discontinuation switch insurance formulary change side effects clinical decline stable disease specialty pharmacists initiated 6 7 dmt discontinuations 49 36 dmt switches strong nonlinear relationship existed age risk nonpersistent p0003 patients injectable index dmt 15 times likely nonpersistence oral dmt 95 ci 1121 p0012 patients noncommercial insurance 14 times likely nonpersistent 95 ci 10220 p0040 conclusionslongterm persistence dmts low many patients switching discontinuing dmt treatment specialty pharmacists identify need dmt discontinuation switch uniquely positioned assist therapy transitions,0.0
disease modifying therapy management multiple sclerosis stem cell therapies retrospective case series abstractbackgroundstem cell therapies sct received formal regulatory approval treatment people multiple sclerosis pwms pwms may seek various options accord current literature largely focuses efficacy safety sct pwms clinical trials particular autologous hematopoietic stem cell transplantation ahsct carefully selected participants little reported ms disease modifying therapy dmt management pwms choose undergo sct outside trialsmethodswe identified pwms two academic centers ms diagnosis fulfilling 2017 mcdonald criteria received sct methodologies permitted ahsct umbilicalderived mesenchymal stem cells adiposederived mesenchymal stem cells admsc goal treat ms 1 1 2015 11 30 2021resultsnine pwms five females age range sct treatment 2569 years old ms disease duration 112 years six relapsingremitting three secondary progressive one primary progressive underwent total eleven scts nine ahsct two admsc one umbilicalderived msc goal treat ms two six pwms underwent sct 10 years ms diagnosis one three pwms underwent stem cell therapies 10 years ms diagnosis clinically stable thereafter ms dmt resumed five pwms afterwards including rituximab ocrelizumab siponimod glatiramer acetate one remained clinically stable whereas four clinically progressed four pwms remained dmt three clinically stable whereas one clinically progressed nine patients demonstrated radiographic stability mri sct one met formal criteria consider ahsct msconclusionswe demonstrate heterogeneous realworld experience treating ms patientchosen experimental scts detailing range dmt management various patient circumstances limitations study include small sample size variety stem cell therapies received,0.0
disease modifying therapy management multiple sclerosis stem cell therapies retrospective case series abstractbackgroundstem cell therapies sct received formal regulatory approval treatment people multiple sclerosis pwms pwms may seek various options accord current literature largely focuses efficacy safety sct pwms clinical trials particular autologous hematopoietic stem cell transplantation ahsct carefully selected participants little reported ms disease modifying therapy dmt management pwms choose undergo sct outside trialsmethodswe identified pwms two academic centers ms diagnosis fulfilling 2017 mcdonald criteria received sct methodologies permitted ahsct umbilicalderived mesenchymal stem cells adiposederived mesenchymal stem cells admsc goal treat ms 1 1 2015 11 30 2021resultsnine pwms five females age range sct treatment 2569 years old ms disease duration 112 years six relapsingremitting three secondary progressive one primary progressive underwent total eleven scts nine ahsct two admsc one umbilicalderived msc goal treat ms two six pwms underwent sct 10 years ms diagnosis one three pwms underwent stem cell therapies 10 years ms diagnosis clinically stable thereafter ms dmt resumed five pwms afterwards including rituximab ocrelizumab siponimod glatiramer acetate one remained clinically stable whereas four clinically progressed four pwms remained dmt three clinically stable whereas one clinically progressed nine patients demonstrated radiographic stability mri sct one met formal criteria consider ahsct msconclusionswe demonstrate heterogeneous realworld experience treating ms patientchosen experimental scts detailing range dmt management various patient circumstances limitations study include small sample size variety stem cell therapies received,1.0
crosssectional analysis persistence diseasemodifying therapies treatment nave experienced patients relapsing multiple sclerosis healthsystem specialty pharmacy abstractbackgroundpatients relapsing multiple sclerosis rms maintained diseasemodifying therapy dmt prevent disease progression reported persistence rates dmts varied concerningly low limited data exists longterm persistence rates reasons dmt discontinuation patients rms study evaluated longterm dmt persistence rates reasons dmt discontinuation switch specialty pharmacist involvement dmt treatment transitions predictors associated nonpersistence treatment nave experienced patientsmethodswe performed singlecenter retrospective crosssectional review patients rms 3 fills dmt healthsystem specialty pharmacy mayoctober 2017 patients followed 3 years determine dmt persistence defined time patient remained index dmt descriptive statistics used summarize sample characteristics outcomes kaplanmeier estimation method used estimate probability remaining persistent used cox proportional hazards regression model analyze primary outcome rates reasons dmt discontinuation identified via pharmacy claims confirmed via chart review electronic health recordresultsthe study included 540 patients 41 76 treatment nave 3 years 193 36 patients remained index dmt probability remaining persistent 3 years 051 95 confidence interval ci 047056 median time index dmt 642 days interquartile range 3171096 347 patients continue index dmt 91 26 discontinued 136 39 switched new dmt 92 27 transferred care new specialty pharmacy provider 21 6 lost followup 7 2 died common reasons dmt discontinuation switch insurance formulary change side effects clinical decline stable disease specialty pharmacists initiated 6 7 dmt discontinuations 49 36 dmt switches strong nonlinear relationship existed age risk nonpersistence p0003 patients injectable index dmt 15 times likely nonpersistent oral dmt 95 ci 1121 p0012 patients noncommercial insurance 14 times likely nonpersistent 95 ci 10220 p0040 conclusionslongterm persistence dmts low many patients switching discontinuing dmt treatment specialty pharmacists identify need dmt discontinuation switch uniquely positioned assist therapy transitions,0.0
treatment anacardic acid modulates dendritic cell activation alleviates disease development autoimmune neuroinflammation mice anacardic acid aa phenolic acid extract found number plants crops fruits exhibits wide range biological activities study displayed aa effectively alleviated eae classical mouse model multiple sclerosis aa administered eae greatly decreased inflammatory cell infiltration cns protected myelin integrity white matter spinal cord aa block lipopolysaccharideinduced dc activation inhibited polarization,1.0
oligodendrocyte death myelin loss cuprizone model updated overview intrinsic extrinsic causes cuprizone demyelination dietary consumption cuprizone copper chelator long known induce demyelination specific brain structures widely used model multiple sclerosis despite extensive use cuprizone mechanism induces demyelination still unknown review provide updated understanding model showcasing two distinct yet overlapping modes action cuprizoneinduced demyelination 1 damage originating within,1.0
making remote measurement technology work multiple sclerosis epilepsy depression survey healthcare professionals conclusions work required quantify benefits rmt clinical practice findings survey suggest wide array clinical team members treating epilepsy ms depression find benefit rmt data care patients findings presented inform implementation rmt digital interventions clinical management range neurological mental health conditions,0.0
catching killer mechanisms programmed cell death immune activation amyotrophic lateral sclerosis central nervous system cns execution programmed cell death pcd crucial proper neurodevelopment however aberrant activation pathways adult cns leads neurodegenerative diseases including amyotrophic lateral sclerosis als cell dies critical can drive local immune activation tissue damage classical apoptosis engages several mechanisms evoke immunologically silent responses whereas forms programmed death pyroptosis,0.0
allostatic load index patients multiple sclerosis casecontrol study elevated allostatic load al index cumulative measure biological dysregulations associated stress exposure reported stress plays important role pathophysiology multiple sclerosis ms however al index investigated population far therefore aimed investigate al index patients ms compared healthy controls total 90 patients relapsingremitting ms 767 females 47 healthy controls 766,0.0
correlation serum levels interleukine16 ccl27 tumor necrosis factorrelated apoptosisinducing ligand bcell activating factor multiple sclerosis severity pathogenic roles interleukine16 il16 ccl27 tumor necrosis factorrelated apoptosisinducing ligand trail bcell activating factor baff shown autoimmune inflammatory diseases aimed correlate circulatory changes factors severity disease patients multiple sclerosis ms casecontrol study conducted 84 ms patients 83 healthy controls measured serum levels il16 ccl27 trail baff,0.0
development validation simple practical method differentiating ms neuroinflammatory disorders based lesion distribution brain mri unmet need develop practical methods differentiating multiple sclerosis ms neuroinflammatory disorders using standard brain mri develop practical approach differentiating ms neuromyelitis optica spectrum disorder nmosd mog antibodyassociated disorder mogad brain mri first identified lesion locations brain suggestive msassociated demyelination ms lesion checklist compared frequencies brain lesions,1.0
melatonin alleviates immune response improves salivary gland function primary sjgrens syndrome primary sjgrens syndrome pss autoimmune disease primarily affects exocrine glands characterized sicca syndrome systemic manifestation mounting evidence indicates circadian clocks involved onset progression autoimmune diseases including rheumatic arthritis multiple sclerosis systemic lupus erythematosus however studies reported expression clock genes pss ideal therapeuticmethod pss management,0.0
effects diseasemodifying treatments discontinuation patients relapsingremitting multiple sclerosis 5 year prospective cohort study abstractbackgroundone challenging issues patients multiple sclerosis discontinuation diseasemodifying treatments dmts subsequent complicationsobjectivewe aimed investigate extent adherence dmts nave multiple sclerosis patients outcomes nonadherence treatments risk factors lead drug discontinuationmaterials methodsin prospective cohort study 288 nave cases relapsingremitting multiple sclerosis rrms age 18 years older included baseline edss expanded disability status scale amounts 2 followed 2015 duration 5 years patients underwent clinical examination every 3 months mri year information recorded moreover patients experienced pregnancy study period excluded main study population evaluated separately end 5year period dmt adherence rate factors affecting treatment continuity effect treatment continuity developed disabilities based edss measured analyzed statistical software spss26 cma37 stata17resultsthe mean age patients 3001 721 years 122 male 878 female treatment adherence rate 825 tiredness treatment prolongation 425 important reason nonadherence treatment additionally significant relationship treatment adherence rate higher education level pvalue0016 married pvalue0006 type dmts glatiramer acetate adjusted or77 rituximab adjusted or383 fingolimod adjusted or381 highest adherence rates however treatment adherence significant relationship age gender employment patients familial histories mean edss patients without drug continuity 5 years 092 109 176 117 respectively showed significant difference pvalue 0001 developed disabilities furthermore survival estimate patients drug adherence higher groupconclusionapproximately one five patients rrms treatment adherence first 5 years treatment type dmt level education marital status factors affect treatment adherence poor treatment adherence associated edss progression multiple sclerosis patients,0.0
effects diseasemodifying treatments discontinuation patients relapsingremitting multiple sclerosis 5 year prospective cohort study abstractbackgroundone challenging issues patients multiple sclerosis discontinuation diseasemodifying treatments dmts subsequent complicationsobjectivewe aimed investigate extent adherence dmts nave multiple sclerosis patients outcomes nonadherence treatments risk factors lead drug discontinuationmaterials methodsin prospective cohort study 288 nave cases relapsingremitting multiple sclerosis rrms age 18 years older included baseline edss expanded disability status scale amounts 2 followed 2015 duration 5 years patients underwent clinical examination every 3 months mri year information recorded moreover patients experienced pregnancy study period excluded main study population evaluated separately end 5year period dmt adherence rate factors affecting treatment continuity effect treatment continuity developed disabilities based edss measured analyzed statistical software spss26 cma37 stata17resultsthe mean age patients 3001721 years 122 male 878 female treatment adherence rate 825 tiredness treatment prolongation 425 important reason nonadherence treatment additionally significant relationship treatment adherence rate higher education level p value0016 married p value0006 type dmts glatiramer acetate adjusted or77 rituximab adjusted or383 fingolimod adjusted or381 highest adherence rates however treatment adherence significant relationship age gender employment patients familial histories mean edss patients without drug continuity 5 years 092109 176117 respectively showed significant difference p value 0001 developed disabilities furthermore survival estimate patients drug adherence higher groupconclusionapproximately one five patients rrms treatment adherence first 5 years treatment type dmt level education marital status factors affect treatment adherence poor treatment adherence associated edss progression multiple sclerosis patients,0.0
third wave cognitive behavioural therapies people multiple sclerosis scoping review conclusions third wave approaches keep refined rigorous investigations needed implement benefit people ms implications rehabilitationmultiple sclerosis linked wide range psychological difficulties adultslittle currently known third wave psychotherapies people msmindfulnessbased stress reduction mindfulnessbased cognitive therapy may helpful address wide range difficulties msspecific,0.0
adipokine signaling pathways osteoarthritis osteoarthritis oa debilitating joint disease affects millions individuals pathogenesis oa fully elucidated obesity wellrecognized risk factor oa multiple studies demonstrated adipokines play key role obesityinduced oa increasing evidence show various adipokines may significantly affect development clinical course oa regulating pro antiinflammatory anabolic catabolic balance matrix remodeling chondrocyte,0.0
occupational therapybased energy management education people postcovid19 conditionrelated fatigue results focus group discussion persons postcovid19 conditions prolonged symptoms longerterm consequences can prevent returning previous everyday functioning fatigue frequent symptom reported literature occupational therapists ots specialized clientcentered problem analysis counseling education recover occupational engagement performance everyday life since beginning covid19 pandemic ots challenged respond services,0.0
predicting disease activity multiple sclerosis patients explainable machine learning approach mavenclad trials multiple sclerosis ms among common autoimmune disabling neurological conditions young adults affects 23 million people worldwide predicting future disease activity ms patients based pathophysiology current treatment pivotal orientate future treatment respect used machine learning predict disease activity status ms patients identify predictive covariates activity analysis conducted pooled,0.0
potential role epstein barr virus multiple sclerosis molecular serological study conclusion conclusions ebna1antibody play significant role development ms significantly higher ms patients controls especially younger age groups early stages disease female patients,0.0
independence urinary symptoms urinary dipstick results voiders neurogenic bladder conclusion among people sci ms void selfadministered urine dipstick results urinary symptom reporting contribute independent information clinical decision making,0.0
improving pediatric multiple sclerosis interventional phase iii study design metaanalysis conclusion metaanalysis provides evidence relapse rates considerably higher ifns versus fingolimod natalizumab results support use innovative bayesian noninferiority designs avoid exposing patients less effective comparators trials bringing new medications patients efficiently,0.0
dimethyl fumarateinduced takotsubo cardiomyopathy patient relapsingremitting multiple sclerosis dimethyl fumarate dmf approved oral pharmacologic agent used treatment relapsingremitting multiple sclerosis rrms although commonly used clinical practice mechanism action remains largely unknown frequent side effects associated drug angioedema hepatic injury flushing herpes zoster infection abdominal pain among others 47yearold female presented symptoms allergic reaction initiating dmf therapy required,0.0
azetidine2carboxylic acidinduced oligodendrogliopathy relevance pathogenesis multiple sclerosis naturally occurring imino acid azetidine2carboxylic acid aze consumed humans can misincorporated place proline myelin basic protein mbp vitro determine aze effects mammalian cns vivo adult cd1 mice given aze orally intraperitoneally clinical signs reminiscent mbpmutant mice occurred 600 mg kg aze exposure aze induced oligodendrocyte ol nucleomegaly nucleoplasm clearing dilated endoplasmic reticulum cytoplasmic,1.0
basal cell carcinoma squamous cell carcinoma patient treated fingolimod multiple sclerosis case report literature review conclusion conclusions dermatological examination performed beginning treatment fingolimod patients need informed risk malignancy patient education crucial treatment allows achieving good therapeutic effect thus minimizing risk malignancy enabling early detection cure,0.0
fingolimodassociated severe bilateral cystoid macular edema conclusions importance findings study show severe bilateral cystoid can occur even several years initiating fingolimod treatment thus indicating detailed followup necessary post cataract surgery,0.0
analysis group pediatric patients relapsingremitting multiple sclerosis data czech national registry conclusion research performed novel diseasemodifying drugs target group,0.0
accurate machine learning model diagnose chronic autoimmune diseases utilizing information b cells monocytes heterogeneity limited comprehension chronic autoimmune disease pathophysiology cause accurate diagnosis challenging process increasing resources singlecell sequencing data reasonable way found address issue study use largescale public singlecell rna sequencing scrnaseq data analysis dataset integration 31 10 pbmcs fifteen sle patients eight healthy donors cellular cross talking 38 10 pbmcs,0.0
targeting physical inactivity using behavioral theory chronic disabling diseases physical inactivity comorbidities eg hypertension result poor prognoses among persons chronic disabling conditions including multiple sclerosis parkinsons disease stroke theory can guide design behavior change interventions can delivered remotely broad scale implementation hypothesize theorybased behavior change interventions can increase physical activity reduce comorbidities associated consequences among persons chronic,0.0
longitudinal tcell responses third sarscov2 vaccination patients multiple sclerosis ocrelizumab fingolimod objectives evaluate whether third vaccination shows added effect severe acute respiratory syndrome coronavirus 2 sarscov2 tcell responses patients multiple sclerosis treated ocrelizumab fingolimod,0.0
impact neuromyelitis optica spectrum disorder quality life patients perspective observational crosssectional study conclusion fatigue pain depressive symptoms frequent problems among patients nmosd impacting quality life assessment patientoriented outcomes may useful achieve holistic approach allowing early specific interventions,0.0
parthenolide suppresses t helper 17 alleviates experimental autoimmune encephalomyelitis t helper th cells play crucial roles inflammation adaptive immune system importantly th17 cells major pathogenic th cell subset involved pathogenesis multiple sclerosis ms classical animal modal experimental autoimmune encephalomyelitis eae previous studies shown parthenolide ptl sesquiterpene lactone possesses potent anticancer antiinflammatory activities however immunosuppressive effect ptl pathogenic th17 cell,1.0
cerebrospinal fluid amyloid precursor protein potential biomarker fatigue multiple sclerosis pilot study abstractbackgroundfatigue major cause disability ms fatigue suggested primary part neurological disease can also secondary diseases outside cns exist separate comorbidity forms measurement currently available subjective standardized questionnaires able identify primary msrelated fatigue therefore need objective biomarkers fatigue ms study explored viability 17 possible biomarkers primary fatigue ms chosen biomarker panel represents function health different parts cnsmethodswe evaluated 31 ms patients 17 healthy controls using fatigue severity scale fss insomnia severity index isi assessed clinical parameters collected csf participants analyze 17 biomarkers multiple targeted sequences reflecting structural functional changes brain based fss scores ms divided msfatigue msf fss 4 msnofatigue msnof fss 4 resultsmsf significantly lower levels amyloid precursor protein app peptides msnof p0005 p0011 biomarker correlating fss group app ms r047 052 p0007 0002 app correlate clinical parameter ms correlated multiple markers ms fss correlated isi months since diagnosisconclusionalthough mechanisms remain unknown altered app metabolism ms seems associated fatigue app evaluated biomarker role structural ms pathology development fatigue individual ms patients,0.0
central neuropathic pain syndromes current emerging pharmacological strategies central neuropathic pain caused disease lesion brain spinal cord difficult predict patients will develop central pain syndromes central nervous system injury depending etiology lifetime prevalence may greater 50 resulting pain often highly distressing difficult treat specific treatment guidelines currently available narrative review discusses mechanisms contributing central neuropathic pain,0.0
mechanistic target rapamycin mtor inhibitor everolimus safely ameliorated lupus nephritis patient complicated tuberous sclerosis 26yearold woman tuberous sclerosis complex tsc received outpatient treatment complication systemic lupus erythematosus sle hospital visited hospital chief complaint pitting edema bilateral lower legs three days urinalysis showed massive proteinuria lot wbc casts blood tests revealed hypoalbuminemia hypercholesterolemia hypocomplementemia elevated antidsdna antibody titer renal biopsy performed,0.0
voxelwise lesion mapping restless legs syndrome multiple sclerosis conclusion voxelwise analysis shows associations subcortex left gyrus precentralis thus data suggests dysfunction efferent motor system due cerebral lesions may contribute pathophysiology rls ms,0.0
biological aging cnsresident cells alters clinical course immunopathology autoimmune demyelinating disease biological aging strongest factor associated clinical phenotype multiple sclerosis ms relapsing remitting ms rrms typically presents third fourth decade mean age presentation progressive ms pms 45 years old show experimental autoimmune encephalomyelitis eae induced adoptive transfer encephalitogenic cd4+ th17 cells severe less like remit middleaged compared young adult mice donor t,1.0
harnessing liver induce antigenspecific immune tolerance autoimmune diseases develop adaptive immune system attacks bodys antigens leading tissue damage least 80 different conditions believed autoimmune aetiology including rheumatoid arthritis type diabetes multiple sclerosis systemic lupus erythematosus collectively autoimmune diseases leading cause severe health impairment along substantial socioeconomic costs current treatments mostly symptomatic nonspecific,0.0
disease modifying therapy switching relapsing multiple sclerosis delphi consensus demyelinating expert group spanish society neurology conclusion agreed statements provide uptodate guidance dmt sequencing optimal patient management,1.0
contact patterns costs multiple sclerosis swedish healthcare systema populationbased quantitative study conclusion considerable differences utilization care cost patients ms unselected population meaning care needs better customized patients demands,0.0
tumefactive multiple sclerosis versus high grade glioma diagnostic dilemma conclusion diagnostic pathway proposed basis specific clinicoradiological features followed patients suspected tdl mri demonstrates lesions typical ms lp demonstrates positive csfspecific ocbs patients undergo short course iv steroids look clinical improvement patients continue deteriorate demonstrate lesions mri lp negative csfspecific ocb considered biopsy,0.0
neuromyelitis optica spectrum disorder rare cause spinal cord optic nerve involvement neuromyelitis optica spectrum disorder nmosd defined rare central nervous system demyelinating autoimmune disorder autoantibodies aquaporin4 commonly affecting females nmosd known also relapsing disease can increase severity episode diagnostic criteria include ruling multiple sclerosis spinal magnetic resonance imaging autoantibody detection management focuses relapse treatment prevention highdose steroids,1.0
case report multiple sclerosis diagnosis anterior lumbar interbody fusion presumed covid19 infection conclusion initial symptoms signs ms may mimic lumbar radiculopathy postviral plexopathy ie due recent covid19 report serve warning future spinal surgeons better differentiate radicular complaints sufficient avoid unnecessary repeated spinal surgery,0.0
nongynaecological applications menstrualderived stem cells systematic review menstrualderived stem cells mensc potential novel source mesenchymal stem cells increased interest investigating therapeutic potential mensc due various advantages exhibit compared types stem cells mensc obtained noninvasively menstrual blood thus collection mensc simple reproducible can carried periodically minimal complications mensc present abundance highly proliferative exhibit,0.0
fluid white matter suppression new sensitive 3 t magnetic resonance imaging contrasts cortical lesion detection multiple sclerosis conclusions cortical lesions identification flawsmin flawshco comparable mp2rageuni combination flawsmin flawshco allowed identify higher number cortical lesions mp2rageuni whereas qt1 maps differ 2 acquisition schemes,0.0
cannabis cannabinoids symptomatic treatment people multiple sclerosis background spasticity chronic neuropathic pain common serious symptoms people multiple sclerosis ms symptoms increase disease progression lead worsening disability impaired activities daily living quality life antispasticity medications analgesics limited benefit poorly tolerated cannabinoids may reduce spasticity pain people ms demand symptomatic treatment cannabinoids high thorough understanding,1.0
prognostic value intrathecal igm synthesis determined various laboratory methods patients early multiple sclerosis prospective observational study abstractbackgroundintrathecal igm synthesis identified adverse prognostic factor patients multiple sclerosis ms however studies confirmed association objective study evaluate clinical utility intrathecal igm synthesis prediction disease activity disability patients first demyelination event msmethodswe conducted singlecentre prospective observational cohort study department neurology university hospital ostrava czech republic intrathecal igm synthesis demonstrated presence cerebrospinal fluidrestricted oligoclonal igm bands calculated using reiber auer hman formula igm indexresultsa total 61 patients clinically isolated syndrome early relapsingremitting ms enrolled analysis 37 women 61 median age disease onset 32 years iqr 25 42 median disease duration 28 years iqr 24 35 thirtyeight 62 patients experienced second relapse ms median 312 days iqr 192 424 29 475 developed magnetic resonance imaging mri activity followup intrathecal igm synthesis affect risk second relapse evidence mri activity univariate multivariate cox regression analysis significant difference disability using expanded disability status scale progression index patients without intrathecal igm synthesisconclusionthis prospective cohort study demonstrate intrathecal igm synthesis risk factor second relapse mri activity associated higher disability patients first demyelinating event,1.0
influence covid19 pandemic lockdown physical activity people multiple sclerosis role online training abstractbackgroundcovid19 pandemic affected people multiple sclerosis pwms various levels pandemic lockdown influenced access typical measures physical activity outdoor training gym exercisesmethodswe performed survey assessing physical activity pandemic lockdown among pwms treated ms center questionnaire encompassed questions regarding physical activity lockdown including employment online technologiesresultsthe survey completed 262 pwms physical activity lockdown declared 744 pwms regular exercises declared 309 participants among physically active pwms 505 limited physical activity covid19 lockdown decrease physical activity reported frequently pwms higher levels disability particularly declaring regular exercises lockdown opinion 39 7 pwms online training replace standard exercises however 19 9 pwms actively looking online training lockdown interest online exercise greatest group 30 years age edss 2 synchronous exercises preferred online training particularly among pwms edss4conclusionour findings indicate need systematic educational organizational measures promoting physical activity among pwms acknowledging pandemic conditions,0.0
antibody response sarscov2 vaccination following typical threedose dosing schedules multiple sclerosis patients treated disease modifying therapies abstractbackground immunizations sarscov2 virus now available recommended effect additional dosing vaccine immunocompromised ms patients unknownmethods part retrospective chart review ms patients vaccinated sarscov2 tested commercially sars covid spike protein antibody march 1 june 30 2021 part ii patients treatment anticd20 infusion medications received sarscov2 third mrna vaccination dose august 13 2021 october 31 2021 subsequently commercially tested sars covid spike protein antibodyresults part total n208 ms patients age range 2376 tested 49 102 208 demonstrating humoral response stratified dmt type patients treated interferon teriflunomide remote history alemtuzumab 2 years since last dmt yielded 100 measurable antibodies 90 amongst patients treated natalizumab fumarates glatiramer acetate 50 measurable antibodies following vaccination s1p modulators anticd20 treated patients subsequently part ii n40 patients anticd20 treatments 33 ocrelizumab 7 rituximab received 3 mrna vaccinations yielded 20 humoral responseconclusions ms patients able mount humoral vaccine response sarscov2 irrespective vaccine type administered patients treated s1p modulators anticd20 agents least likely mount response typical dosing schedule patients treated ocrelizumab rituximab show similar modest humoral immune system benefit following three doses standard dosing,0.0
nmethyldaspartate nmda type glutamate receptors demyelinating disorders neuroimmune perspective nmethyldaspartate receptors nmdars ionotropic glutamate receptors highly important regulating substantial physiologic processes brain nervous system disturbance function contribute different pathologies overstimulation hyperactivity nmdars termed glutamate toxicity promote cell death apoptosis meanwhile blockade lead dysfunction brain nervous system well growing body evidence,1.0
versican promotes t helper 17 cytotoxic inflammation impedes oligodendrocyte precursor cell remyelination remyelination failure multiple sclerosis ms contributes progression disability deficient repair results neuroinflammation deposition inhibitors including chondroitin sulfate proteoglycans cspgs cspg member repairinhibitory alters local inflammation exacerbate injury unknown correlate high versicanv1 expression ms lesions deficient premyelinating oligodendrocytes highlight selective upregulation amongst cspg members,1.0
short report reallife analysis occurrence persistent transient fluctuating positive titres neutralizing antidrug antibodies multiple sclerosis patients treated interferon beta interferon beta ifn first line therapy treatment multiple sclerosis ms however 47 treated patients will develop neutralizing antidrug antibodies nabs ifn high titres can inhibit therapeutic effect drug study aimed determine frequency transient fluctuating nab positivity realworld clinical routine setting using large retrospective international cohort ifntreated ms patients collected part,0.0
sphingosine 1phosphate receptortargeted therapeutics rheumatic diseases sphingosine 1phosphate s1p acts via g proteincoupled s1p receptors s1prs bioactive lipid essential vascular integrity lymphocyte trafficking s1ps1pr signalling axis key component inflammatory response autoimmune rheumatic diseases several drugs target s1prs approved treatment multiple sclerosis inflammatory bowel disease clinical testing patients systemic lupus erythematosus sle preclinical,0.0
assessment data consistency cascades independently recurrent inference machines fast robust accelerated mri reconstruction objectivemachine learning methods can learn reconstruct magnetic resonance images mri thereby accelerate acquisition paramount importance clinical workflow physicsinformed networks incorporate forward model accelerated mri reconstruction learning process increasing network complexity robustness ensured reconstructing data unseen training aim embed data consistency dc deep networks balancing degree,0.0
safety profile sarscov2 vaccination patients antibodymediated cns disorders objectives retrospective multicenter study evaluated safety sarscov2 vaccination patients harboring autoantibodies targeting neuronal surface synaptic antigens,0.0
immunology multiple sclerosis incomplete understanding causes pathways involved onset progression multiple sclerosis ms limits ability effectively treat complex neurological disease recent studies explore role immune cells different stages ms interact cells central nervous system cns findings presented begin question exclusivity antigenspecific cause highlight seemingly distinct immune cell types can share,0.0
microbiota alterations proline metabolism impact depression microbiotagutbrain axis emerged novel target depression disorder low treatment efficacy however field dominated underpowered studies focusing major depression addressing microbiome functionality compositional nature confounding factors applied multiomics approach combining preclinical models three human cohorts including patients mild depression microbial functions metabolites converging onto glutamate gaba metabolism,0.0
toxic sod1 trimers offpathway formation amyloidlike fibrils als accumulation insoluble amyloid fibrils widely studied critical factor pathology multiple neurodegenerative diseases including amyotrophic lateral sclerosis als fatal neurodegenerative disease misfolded cu zn superoxide dismutase sod1 first protein linked als nonnative sod1 trimeric oligomers recently linked cytotoxicity larger oligomers protective cells balance trimers larger aggregates process sod1,0.0
designing characterization tregitopebased multiepitope vaccine multiple sclerosis immunoinformatic approach conclusion computational analysis demonstrated vaccine harnessing pathogenic t cells can control ms disease progression even disease relapse,1.0
fibrintargeting molecular mri inflammatory cns disorders conclusions molecular imaging cns fibrin deposition provides imaging biomarker inflammatory cns pathology corresponds pathophysiological ecm remodelling disease activity yields high signaltonoise ratio can improve diagnostic neuroimaging across several neurological diseases variable degrees barrier impairment,0.0
bivalent epsteinbarr virus vaccine induces neutralizing antibodies block infection confer immunity humanized mice epsteinbarr virus ebv major cause infectious mononucleosis associated several human cancers recently multiple sclerosis despite prevalence health impact currently vaccines treatments four viral glycoproteins gp gp350 gh gl gp42 mediate entry major sites viral replication b cells epithelial cells designed nanoparticle vaccine displaying proteins showed elicits potent neutralizing,0.0
impact previous diseasemodifying treatment safety efficacy patients ms treated ahsct conclusion study provides level 4 evidence ahsct patients previously treated alemtuzumab cladribine rituximab safe efficacious,1.0
oneandahalf syndrome initial presentation multiple sclerosis abstract,0.0
fatigue sleepiness depression multiple sclerosis defining overlaps better phenotyping background objectives define boundaries overlaps fatigue sleepiness depression patients multiple sclerosis ms using different tools dimension including instrumental sleep analysis,0.0
cardiovascular autonomic dysfunction multiple sclerosisfindings relationships clinical outcomes fatigue severity conclusion cardiovascular autonomic modulation altered ms highly dependent disease variant disability level fatigue severity patients demographics,0.0
impact covid19 pandemic psychological status cortisol level multiple sclerosis patients study aimed compare changes psychological status cortisol level multiple sclerosis ms patients healthy control group hc one hundred fiftyfive ms patients 165 hc subjects completed questionnaires consisting 36item short health survey sf36 hamilton anxiety rating scale hama beck depression inventoryii bdiii fatigue severity score fss one year onset covid19 pandemic salivary cortisol level,0.0
th17 cells promote cns inflammation sensing danger signals via mincle ctype lectin receptor mincle known important role innate immune cells recognizing pathogen damage associated molecular patterns report t cellintrinsic role mincle pathogenesis experimental autoimmune encephalomyelitis eae genomic deletion mincle t cells impairs th17 th1 cellmediated eae alignment significantly higher expression mincle th17 cells th1 cells mechanistically dying cells release,0.0
microglia brain development regeneration recently emerged microglia tissueresident macrophages central nervous system play significant noninnate immune roles support development maintenance homeostasis repair brain apart highly specialized brain phagocytes microglia modulate development functions neurons glial cells direct indirect interactions thus recognizing elements influence homeostasis heterogeneity microglia,0.0
targeted delivery platforms treatment multiple sclerosis multiple sclerosis ms neurodegenerative condition central nervous system cns presents varying levels disability patients displaying significance timely effective management complication though several treatments developed protect nerves comprehensive improvement ms still considered essential bottleneck therefore development innovative treatment methods ms one core research areas regard,0.0
neuromyelitis optica spectrum disorder postcovid19 infection rare case report northeast india multiple sclerosis neuromyelitis optica spectrum disorder may seen acute setting coronavirus disease 2019 covid19 infection even postrecovery patients may present optic neuropathy along weakness back lower limbs ascending paralysis can present respiratory distress acute covid19 infection may even prove fatal report unique case 16yearold female past history covid19 infection optic neuropathy,0.0
systematic analysis genegene interaction multiple sclerosis conclusions study showcases ability epigwas uncover biologically interpretable epistatic interactions potentially actionable development combination therapy,0.0
lipocalin2 influence eae clinical score increases inflammation central nervous system contribution lipocalin2 lcn2 multiple sclerosis ms controversial herein induced experimental autoimmune encephalomyelitis eae lcn2null wildtype wt mice find differences genotypes regarding clinical score lcn2null eae mice presented decreased expression interferon gamma diminished demyelination cerebellum genotypes presented similar alterations thymocyte splenocyte populations ms patients higher,1.0
acute axon damage demyelination mitigated 4aminopyridine 4ap therapy experimental traumatic brain injury damage long axons white matter tracts major pathology closed head traumatic brain injury tbi acute tbi treatments needed protect axon damage promote recovery axon function prevent long term symptoms neurodegeneration prior characterization axon damage demyelination tbi led us examine repurposing 4aminopyridine 4ap fdaapproved inhibitor voltagegated potassium kv channels 4ap currently indicated provide,1.0
difference safety humoral response mrna sarscov2 vaccines patients autoimmune neurological disorders ancovax study conclusion sarscov2 mrna vaccines safe large group anc patients anticd20 fingolimod treatment well vaccination bnt162b2 vaccine led reduced humoral response findings inform vaccine policies anc patients undergoing immunotherapy,0.0
axonal injury asymptomatic individuals preceding onset multiple sclerosis axonal loss main cause irreversible disability multiple sclerosis ms serum neurofilament light snfl biomarker axonal disintegration nested casecontrol study blood samples 519 presymptomatic persons age range 439 years later received ms diagnosis showed higher snfl concentrations 519 matched controls p 00001 noticeable least 10 years clinical ms onset mean values prems control groups 96 pg ml versus 74 pg ml,0.0
correction covid19 outcomes vaccination people relapsing multiple sclerosis treated ofatumumab abstract,0.0
collective health research assessment developing tool measure impact multistakeholder research initiatives conclusions msc example views society can taken account research impacts assessed sustainable balanced way engagement patients stakeholders integral part crif facilitating collaborative decisionmaking design policies research agendas policy making collective approach allows evaluation perspective extended needs society towards responsible research,0.0
recombinant ctype lectin protein toxocara canis increases population spleen foxp3+ regulatory t cells balb c mice toxocara canis t canis common parasitic nematode dogs cats parasitic worms can cause chronic longterm infections host due ability neutralize hosts defense mechanisms can stimulate immune responsemediated regulatory t treg cells aim study evaluate effect recombinant t canis ctype lectin protein tctl1 cell infiltration brains balb c mice well number regulatory t cells sixweekold,0.0
epsteinbarr virus envelope glycoprotein gp350 tricks cr2 molecular dynamics study connection epstein barr virus ebv diseases burkitt lymphoma hodgkin disease multiple sclerosis systemic lupus erythematosus various bcell lymphomas made ebv glycoproteins one popular vaccine immunogens protein encoded ebv viral membrane envelope protein gp350 studied extensively due abundancy surface interaction complementary receptor cr2 binding cr2 gp350 leads entrance,0.0
diseasemodifying drugs breastfeeding multiple sclerosis narrative literature review pregnancyrelated issues women multiple sclerosis ms receiving increasing attention particular interest use diseasemodifying therapies dmts conception pregnancy postpartum including breastfeeding risk relapse higher early postpartum period especially cases significant disease activity prior pregnancy thus treatment resumption switching strategies might necessary moreover breastfeeding,0.0
impact pathological conditions postural reflex latency adaptability following unpredictable perturbations systematic review metaanalysis conclusions systematic review demonstrated postural reflexes significantly delayed people multiple sclerosis +22 ms stroke +34 ms diabetes +19 ms hiv +9 ms incomplete spinal cord injury +57 ms back knee pain +12 ms pathological conditions characterized impaired sensation neural function contrast timing postural reflexes impaired people parkinsons disease cerebellar dysfunction confirming limited involvement,0.0
optic neuritis potential poor outcome optic neuritis treatment trial previously reported corticosteroids accelerated visual recovery optic neuritis without improving outcome finding related largely multiple sclerosis ms subsequently neurologists tended await spontaneous recovery since nonms cases identified antibodies aquaporin4 aqp4 myelin oligodendrocyte glycoprotein mog disorders can closely mimic multiple sclerosisassociated idiopathic,1.0
darq deep learning quality control stereotaxic registration human brain mri t1w mniicbm 152 template linear registration stereotaxic space common first step many automated imageprocessing tools analysis human brain mri scans step crucial success subsequent imageprocessing steps several wellestablished algorithms commonly used field neuroimaging task none 100 success rate manual assessment registration commonly used part quality control reduce burden timeconsuming step propose,0.0
effect photobiomodulation fatigue individuals relapsingremitting multiple sclerosis pilot study multiple sclerosis autoimmune disease central nervous system characterized inflammation destruction myelin sheath fatigue one main symptoms disease negative impact quality life treatment options photobiomodulation used several inflammatory conditions may beneficial treatment fatigue individuals multiple sclerosis conduct pilot study analyze effect photobiomodulation fatigue,1.0
visual evoked potentials monitor myelin cuprizoneinduced functional changes visual system one accessible routes study central nervous system pathological conditions multiple sclerosis ms noninvasive visual evoked potential vep optical coherence tomography oct used assess visual function neuroretinal thickness c57bl 6 taking 02 cuprizone 7 weeks 5 8 12 15 days returning normal diet veps significantly delayed starting 4 weeks cuprizone progressive,1.0
doubleblind placebocontrolled singleascendingdose intravenous infusion study rhigm22 subjects multiple sclerosis immediately following relapse conclusion although limited high variability small sample size data suggest enhanced cns uptake associated drop csf levels study demonstrated safety antibody directed myelin oligodendrocytes course active demyelinating disease research rhigm22 warrantedclinicaltrialsgov nct02398461 https clinicaltrialsgov ct2 show study nct02398461termm22draw2rank8,1.0
treatment ifb088 improves neuropathy cmt1a cmt1b mice charcotmarietooth disease type 1a cmt1a caused duplication peripheral myelin protein 22 pmp22 gene cmt1b caused mutations myelin protein zero mpz gene two common forms demyelinating cmt cmt1 treatments available either prior studies mpzser63del mouse model cmt1b demonstrated protein misfolding endoplasmic reticulum er retention activation unfolded protein response upr contributed,1.0
recent trends practices toward assessment rehabilitation neurodegenerative disorders insights human gait study human movement biomechanics forms integral part various clinical assessments provides valuable information toward diagnosing neurodegenerative disorders motor symptoms predominate conventional gait postural balance analysis techniques like force platforms motion cameras etc complex expensive equipment requiring specialist operators thereby posing significant challenge toward translation clinics current manuscript presents,0.0
group resilience training program people multiple sclerosis study protocol multicentre clusterrandomized controlled trial multiready ms conclusion expected study will contribute body evidence efficacy effectiveness ready comparing active group intervention frontline ms rehabilitation clinical settings results will disseminated peerreviewed journals relevant conferences,0.0
treatment challenges multiple sclerosis continued role glatiramer acetate earlier diagnosis access diseasemodifying therapies dmts improved supportive care favorably altered disease course multiple sclerosis ms leading improvement longterm outcomes people ms pwms success changed medical characteristics population seen ms clinics comorbidities accompanying polypharmacy immune senescence growing number approved dmts make selecting optimal agent individual patient,0.0
renal function body mass index contribute serum neurofilament light chain levels elderly patients atrial fibrillation objective serum neurofilament light chain snfl increasingly used neuroaxonal injury biomarker elderly besides age little known physiological factors like renal function body mass index bmi alter levels investigated association estimated glomerular filtration rate egfr bmi snfl large sample elderly patients atrial fibrillation af,0.0
determinants physical activity women multiple sclerosis based theory planned behavior conclusion findings indicate constructs tpb used behavioral interventions healthcare providers increasing pa among women ms,0.0
comparison employment among people multiple sclerosis across europe conclusions found remarkable differences european registers countries studied may indicate inequalities european level furthermore findings suggest feasible useful combine data different ms registers europe albeit data structures heterogeneous,0.0
brain mri dataset multiple sclerosis consensus manual lesion segmentation patient meta information magnetic resonance imaging mri provides significant key diagnose monitor progression multiple sclerosis ms disease manual mslesion segmentation expanded disability status scale edss patients meta information can provide gold standard research terms automated mslesion quantification automated edss prediction identification correlation mslesion patient disability dataset provide novel multisequence mri dataset,0.0
early vs late treatment initiation multiple sclerosis impact cost illness registerbased prospective cohort study sweden conclusions early dmt ms result lower productivity losses possibly maintained work capacity coi serves objective measure showing advantage early vs late treatment initiation ms,0.0
loss thymic function promotes eae relapse anticd52treated mice anticd52 treatment creates longlasting cd4 t cell lymphopenia reduces multiple sclerosis ms relapses humans contrast anticd52 therapy disease onset fully suppresses experimental autoimmune encephalomyelitis eae mice t cell repopulation rapid test whether prolonged t cell lymphopenia promotes relapses thymectomized mice prior eae induction anticd52 treatment thymectomy greatly reduced number recent thymic emigrant t cells,0.0
enigmatic links epsteinbarr virus infection multiple sclerosis abstract,0.0
pain symptoms optic neuritis signs symptoms optic neuritis autoimmune disorder central nervous system cns differ patients pain commonly reported patients may major reason patients visit clinic article reviews presence pain related respect underlying disorders including multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd myelin oligodendrocyte glycoprotein associated disease mogad aim,1.0
use benzodiazepines zdrugs multiple sclerosis conclusion use bzd common people ms general population controls use agents persons ms often chronic,0.0
true burden heart failure among multiple sclerosis patients addressing potential publication bias summarypublication bias potential source concern many metaanalyses published contemporary literature new improved method detection publication bias doi plot several advantages counterpart funnel plot doi plot can accurately assess publication bias even number studies less ten pooling proportions additionally utility google scholar supplementary database identify relevant studies gray literature needs highlighted due indexation large volumes articles,0.0
validity reliability 3meter backward walk test patients multiple sclerosis abstractbackgroundthe 3meter backward walk test 3mbwt evaluates neuromuscular control proprioception protective reflexes fall risk balance study aimed examine reliability validity minimal detectable change mdc 3mbwt patients multiple sclerosis pwms methods40 pwms 8 male 32 female included study intraclass correlation coefficient icc used reliability 3mbwt mdc estimates calculated using baseline data validity 3mbwt evaluated correlation timed go test tug 12item multiple sclerosis walking scale msws12 2minute walk test 2mwt timed 25foot walk test t25fw four square step test fsst resultsthe intrarater icc 09440945 interrater icc 09320935 reliability 3mbwt determined excellent mdc values intrarater 113130 sec mdc values interrater 110124 sec correlation 3mbwt tug msws12 2mwt found statistically significantconclusionthe 3mbwt found valid reliable pwms short easily applied test outpatient inpatient clinics without need equipment according mdc results small differences pwms can adequately detected 3mbwt therefore may clinically suitable test detecting subtle changes synergistic motor functions related prorioception relapsing remitting periods also may add information edss data following disease progression well treatment responses,0.0
late onset neuromyelitis optica spectrum disorders lonmosd nationwide portuguese study antiaqp4 positive antimog positive seronegative subgroups abstractintroductionseveral neuroimmunological disorders distinct phenotypes according age onset multiple sclerosis myasthenia gravis also described late onset nmosd lonmosd different phenotypeobjectiveto describe clinical demographic characteristics lonmosd distinguish early onset eonmosd methodsfrom nationwide portuguese nmosd study analyzed clinical demographic characteristics lonmosdresultsfrom 180 portuguese patients 45 disease onset 50 years old 80 female 23 antiaqp4 antibodies 511 13 antimog antibodies 289 9 double seronegative 200 common presenting phenotypes lonmosd transverse myelitis 533 optic neuritis 267 without difference eonmosd p0074 mean edss lonmosd 60 sd28 mean followup time 458 sd447 years significantly greater mean edss eonmosd 325 sd180 p0022 antiaqp4 antibodies positive lonmosd patients increased disability compared antimog antibodies positive lonmosd p0022 survival analysis showed reduced time use cane lonmosd irrespective serostatus p0001 conclusionslonmosd increased disability faster progression despite differences presenting clinical phenotype seen cohort,0.0
fatigue brain atrophy egyptian patients relapsing remitting multiple sclerosis abstractbackground fatigue troublesome symptom relapsing remitting multiple sclerosis rrms starts early disease course escalates disease progression impacts patients quality life aim work estimate frequency fatigue evaluate relationship severity fatigue clinical data level disability volumetric brain atrophy rrmsmethods 43 rrms patients 40 age sexmatched normal volunteers recruited demographic clinical data recorded participant assessed expanded disability status scale edss fatigue severity scale fss brief cognitive assessment multiple sclerosis bicams variety brain volumetric measuresresults 31 721 rrms patients found fatigue significant differences demographic data patients without fatigue according fss however patients fatigue higher number attacks higher scores edss bicams nonfatigued patients greater reduction total brain volume cerebral grey matter brain stem thalamic caudate volumes fatigued compared nonfatigued patients controls fss significantly correlated patients age duration illness total number attacks edss bicams total brain cerebral grey matter thalamic volumes negative correlations fatigue severity regression analysis showed edss accounted 46 variance fatigue scores thalamic brainstem atrophy accounted 507conclusion fatigue fairly common rrms patients level disability atrophy thalamus brain stem best predictors fatigue,0.0
fatigue brain atrophy egyptian patients relapsing remitting multiple sclerosis abstractbackgroundfatigue troublesome symptom relapsing remitting multiple sclerosis rrms starts early disease course escalates disease progression impacts patients quality life aim work estimate frequency fatigue evaluate relationship severity fatigue clinical data level disability volumetric brain atrophy rrmsmethods43 rrms patients 40 age sexmatched normal volunteers recruited demographic clinical data recorded participant assessed expanded disability status scale edss fatigue severity scale fss brief cognitive assessment multiple sclerosis bicams variety brain volumetric measuresresults31 721 rrms patients found fatigue significant differences demographic data patients without fatigue according fss however patients fatigue higher number attacks higher scores edss bicams nonfatigued patients greater reduction total brain volume cerebral grey matter brain stem thalamic caudate volumes fatigued compared nonfatigued patients controls fss significantly correlated patients age duration illness total number attacks edss bicams total brain cerebral grey matter thalamic volumes negative correlations fatigue severity regression analysis showed edss accounted 46 variance fatigue scores thalamic brainstem atrophy accounted 507conclusionfatigue fairly common rrms patients level disability atrophy thalamus brain stem best predictors fatigue,0.0
true burden heart failure among multiple sclerosis patients addressing potential publication bias summarypublication bias potential source concern many metaanalyses published contemporary literature new improved method detection publication bias doi plot several advantages counterpart funnel plot doi plot can accurately assess publication bias even number studies less ten pooling proportions additionally utility google scholar supplementary database identify relevant studies grey literature needs highlighted due indexation large volumes articles,0.0
validity reliability 3meter backward walk test patients multiple sclerosis abstractbackgroundthe 3meter backward walk test 3mbwt evaluates neuromuscular control proprioception protective reflexes fall risk balance study aimed examine reliability validity minimal detectable change mdc 3mbwt patients multiple sclerosis pwms methods40 pwms 8 male 32 female included study intraclass correlation coefficient icc used reliability 3mbwt mdc estimates calculated using baseline data validity 3mbwt evaluated correlation timed go test tug 12item multiple sclerosis walking scale msws12 2min walk test 2mwt timed 25foot walk test t25fw four square step test fsst resultsthe intrarater icc 09440945 interrater icc 09320935 reliability 3mbwt determined excellent mdc values intrarater 113130 sec mdc values interrater 110124 sec correlation 3mbwt tug msws12 2mwt found statistically significantconclusionthe 3mbwt found valid reliable pwms short easily applied test outpatient inpatient clinics without need equipment according mdc results small differences pwms can adequately detected 3mbwt therefore may clinically suitable test detecting subtle changes synergistic motor functions related prorioception relapsing remitting periods also may add information edss data following disease progression well treatment responses,0.0
modeling neurodegenerative disorders zebrafish neurodegeneration major cause alzheimers parkinsons huntingtons multiple amyotrophic lateral sclerosis pontocerebellar hypoplasia dementia brain disorders complex pathogenesis commonly includes genetic neurochemical deficits misfolded protein toxicity demyelination apoptosis mitochondrial dysfunctions albeit differing specific underlying mechanisms neurodegenerative disorders typically display evolutionarily conserved mechanisms across taxa,1.0
german guideline diagnosis treatment multiple sclerosis survey focusing neurologists daily practise performed webbased survey among germanspeaking neurologists evaluate acceptance 2021 german guideline diagnosis treatment multiple sclerosis based 327 replies total current survey largely reproduced findings earlier smaller survey prefinal consultation version guideline confirmed high acceptance rates half participants practising neurologists neurologists ms centers 500 patients per year,0.0
association depression obesity creactive protein germany large nationally representative study conclusions data suggest obesity status strongly associated increased inflammation depressive symptoms mdd relationship depression hscrp populationbased sample substantially influenced obesity status well medical factors lifestyle socioeconomic status furthermore findings suggest association hscrp depression symptomspecific rather generalized,0.0
evaluation cerebrospinal fluid neurofilament light chain levels multiple sclerosis nondemyelinating diseases central nervous system clinical biochemical perspective neurofilament light chain nfl promising biomarker diagnosis prognosis treatment response evaluation neurological diseases aims study compare cerebrospinal fluid csf nfl levels multiple sclerosis ms certain nondemyelinating diseases central nervous system ndcns determine relationship clinical radiological features csf nfl levels patients ms compare enzymelinked immunosorbent assay,1.0
meningeal lymphatic vasculature neuroinflammation abstractthe lymphatic vasculature unidirectional network lymphatic endothelial cells whose main role maintain fluid homeostasis along absorption dietary fat gastrointestinal organs management coordination immune cell trafficking lymph nodes homeostasis inflammatory conditions homeostatic conditions immune cells dendritic cells macrophages t cells can enter lymphatic vasculature move easily lymph reaching secondary lymph nodes immune cell activation peripheral tolerance can modulated however inflammatory conditions pathogen infection increased permeabilization lymphatic vessels allows faster immune cell migration inflamed tissues following chemokine gradient facilitating pathogen clearance resolution inflammation interestingly since rediscovery lymphatic vasculature central nervous system known meningeal lymphatic vasculature role lymphatics key player several neurological disorders described emphasis neurodegenerative process alternatively less discussed meningeal lymphatics role neuroinflammation review discuss current knowledge anatomy function meningeal lymphatic vasculature specifically analyze contribution different neuroinflammatory processes highlighting potential therapeutic target meningeal lymphatic vasculature pathological conditions,0.0
neuroimmunomodulatory balance pro antiinflammatory cytokines regulate mcov induced alteration gap junction protein cx43 mouse hepatitis virus mhv murine cov experimental model used understand viralinduced acute neuroinflammation chronic progressive demyelination characteristic hallmarks human neurological disease multiple sclerosis mhv induced neuroinflammation provides excellent causeeffective platform understand virus can initiate neuroinflammation causing direct neuroglial cell dystrophy leading chronic progressive myelin damage without concurrent axonal loss previous studies postulated significant nexus host proteins also involved regulating host response viral replication one protein transmembrane protein connexin 43 cx43 belonging gap junction family cx43 one abundant gap junction proteins astrocytes responsible metabolic coupling cns cells maintain homeostasis mhv infection mice results significant decrease expression cx43 acute stage day 56 mhv infection viral titer reaches peak brain presents acute encephalitis characterized perivascular cuffing microglial nodule formation surprisingly cx43 returns normal levels infectious viral particles go detection limit day 10 pi marks transition innate immune responses adaptive immunity interestingly reduced expression cx43 day 5 accords increased proinflammatory cytokines oxidative stress activation upr pathway proteins study investigated transcriptional regulation tnf il6 il10 il1 tgf alteration cx43 expression trafficking day 5 6 day 10 post mhv infection tnf il10 il6 il1 major inflammatory cytokines upregulated acute stage mhv infection 56 pi additionally tnf il1 known negative regulators cx43 expression attributed decrease cx43 observed studies furthermore studies also revealed mhv infection apart high expression il10 another antiinflammatory cytokine tgf expression increases proinflammatory milieu cytokines shifts towards antiinflammatory condition inflamed brain tgf positive regulator cx43 may responsible restoration cx43 expression trafficking cell surface resulting functional gap junctional communication reestablishment intercellular communication maybe essential bring back homeostasis inflamed brain balance proinflammatory cytokines antiinflammatory mediators may regulate host response counteract viral infection altering gap junctional communication study thus presents crucial evidence support nexus immune inflammatory mediators host regulatory responders mhv induced neuroinflammation,1.0
matrine inhibits wnt3a catenin tcf7l2 signaling pathway experimental autoimmune encephalomyelitis oligodendrocyte ol death remyelination failure lead progressive neurological deficits multiple sclerosis ms animal model experimental autoimmune encephalomyelitis eae matrine mat quinolizidine alkaloid component derived root sophora flavescens capacity effectively inhibit central nervous system cns inflammation promote neuroregeneration present study explored regulatory mechanism wnt catenin tcf7l2 pathway,1.0
wuzi yanzong pill attenuates mptpinduced parkinsons disease via pi3k akt signaling pathway wuzi yanzong pill wyp found play protective role nerve cells neurological diseases however molecular mechanism unclear understand molecular mechanisms underly neuroprotective effect wyp dopaminergic neurons parkinsons disease pd pd mouse model induced 1methyl4phenyl1 2 3 6tetrahydropyridine mptp gait hanging tests used assess motor behavioral function immunofluorescence assay used determine thpositive,1.0
nurr1 modulation mediates neuroprotective effects statins ligandsensing transcription factor nurr1 emerges promising therapeutic target neurodegenerative pathologies nurr1 ligands functional studies therapeutic validation lacking pronounced nurr1 modulation statins clinically relevant neuroprotective effects demonstrated reported several statins directly affect nurr1 activity cellular cellfree settings low micromolar submicromolar potencies simvastatin example exhibits,1.0
cyclindependent kinase 7 contributes myelin maintenance adult central nervous system promotes myelin gene expression mechanisms regulating oligodendrocyte differentiation developmental myelination myelin maintenance adulthood complex still completely described understanding crucial development new protective therapeutic strategies demyelinating pathologies multiple sclerosis perspective investigated role cyclindependent kinase 7 cdk7 kinase involved cellcycle progression transcription regulation,1.0
abcb1 gene polymorphisms impact effect highdose intravenous methylprednisolone therapy optic neuritis associated aqp4iggpositive neuromyelitis optica spectrum disorder known objective patients optic neuritis significant individual differences response highdose intravenous methylprednisolone himp therapy study aims evaluate association gene polymorphisms efficacy himp therapy chinese han patients mediated aquaporin4 immunoglobulin g antibody aqp4igg positive neuromyelitis optica spectrum disorder nmosd multiple sclerosis ms,0.0
clinical mri predictors cognitive decline patients relapsingremitting multiple sclerosis 2year longitudinal study abstractbackground study conducted prospective 2year cohort patients rrms healthy controls hcs investigate rate clinical imaging predictors cognitive decline relapsingremitting multiple sclerosis rrms methods total 107 patients clinically definite rrms 74 hcs recruited hebei general hospital shijiazhuang hebei patients assessed minimal assessment cognitive function ms macfims baseline 2year followup visits classified cognitivelydeclining cognitivelystable rrms baseline demographic clinical imaging parameters inserted separate multivariate regression models investigate predictive power factors future cognitive declineresults based classification protocol data hcs 355 rrms patients categorized cognitivelydeclining multivariate logistic regression analyses demonstrated disease duration edss average disease attack year clinical parameters significant predictive value future cognitive decline r20344 within wholebrain mri measures total brain cortical grey matter gm subcortical gm volumes significantly predict cognitive decline r20566 wm lesion volume also significantly predict cognitive decline r20645 within lobar brain measures frontal temporal lobe volumes r20666 finally within subcortical gm volumes hippocampus pallidum putamen thalamus predictive future cognitive decline r20732 conclusions findings suggest rrms patients disease severity higher gm atrophy increased wm lesion volume susceptible cognitive decline studies assess underpinnings cortical subcortical atrophy lead cognitive decline rrms patients,0.0
influence diseasemodifying therapy hidden disability burden people newly diagnosed relapsingremitting multiple sclerosis abstractbackground addition motor disability hidden disability depression anxiety fatigue sleep disturbance cognitive impairment pain major complaint people multiple sclerosis explored changes hidden disability burden early postdiagnostic period examined hypothesis disease modifying therapies beneficial effect hidden disability burdenmethods adults recently diagnosed 6 months relapsingremitting multiple sclerosis n440 mean age 374104 76 female national multicentre cohort study futurems underwent testing clinical neuropsychological instruments well brain mri baseline 12months disease modifying therapies started baseline assessment classified injectables n70 interferons glatiramer acetate dmts n215 dmt n117 reference sensitivity analyses undertaken using alternative classifications disease modifying therapy vs none 3category system performed latent transition analysis hidden disability burden latent variable including propensity score weightsresults identified three classes low 58 moderate 25 high 17 hidden disability burden 70 transition unchanged reference 26 transitioned lower burden class improvement 4 transitioned higher burden class worsening median treatment duration 11 months iqr 912 injectables 13 95cis 07 23 p04 dmts 14 95cis 09 21 p02 associated significant change hidden disability burden either direction improvement worsening alternative 3category classification category 2 treatment fingolimod cladribine n22 associated improvement 43 26 70 p0001 conclusion hidden disability present newly diagnosed people multiple sclerosis majority remained unchanged approximately quarter improved immediate postdiagnostic period disease modifying therapy significant influence hidden disability burden study period one year following diagnosis trend towards favourable outcomes fingolimod cladribine interpreted caution due small sample size exploratory data observational scope attendant biases highlight need study including longerterm evaluation well randomised trials nonmotor disability,0.0
epidemiological analysis multiple sclerosis patients hospitalized united states available,0.0
epidemiological analysis multiple sclerosis patients hospitalized united states available,0.0
using ms induced pluripotent stem cells investigate ms aetiology abstractmultiple sclerosis ms complex disease pathophysiology impacts function immune central nervous system cell types despite extensive investigation aetiology ms underlying cause s remain elusive consequently faithful vitro vivo preclinical models ms exist advances human stem cell technologies enabled generation induced pluripotent stem cells ipscs people ms review summarises discoveries made using ipscs derived people ms explores current potential application s ms research,0.0
mirnas multiple sclerosis clinical approach abstractmicrornas mirnas noncoding single stranded segments rna measuring 19 25 nucleotides length play active role autoimmune diseases including multiple sclerosis ms structures studied given implication process diagnosis disease development treatment prognosis ms given progressive neurodegenerative nature ms mirnas identified critical mediators molecular pinpoints disease poses excellent candidates obtention suitable biomarkers treatment targets review condenses recent findings role mirnas multiple sclerosis including role ms etiology molecular mechanisms disease exploitation mirnas diagnostic tools biomarkers mirnas treatment option target ms significance predictors disease prognosis,1.0
design methodological characteristics studies using observational routinely collected health data investigating link cancer neurodegenerative diseases protocol metaresearch study introduction health services generate large amounts routine health data eg administrative databases disease registries electronic health records important secondary uses research increases availability ability access analyse large amounts data represent major opportunity conducting studies possible relationships complex diseases objective study will evaluate design methods reporting studies,0.0
machine learning reveals distinct gene signature profiles lesional nonlesional regions inflammatory skin diseases analysis gene expression cutaneous lupus erythematosus psoriasis atopic dermatitis systemic sclerosis using gene set variation analysis gsva revealed lesional samples condition unique features four diseases displayed common enrichment multiple inflammatory signatures findings confirmed classification regression tree analysis machine learning ml models nonlesional samples disease also differed normal,0.0
cd4sup+ supcmetsup+ supitg4sup+ sup t cell subset promotes murine neuroinflammation objective cmet tyrosine kinase receptor unique receptor hepatocyte growth factor hgf hgf cmet axis reported modulate cell migration maturation cytokine production antigen presentation report cd4 + cmet + t cells detected increased levels experimental autoimmune encephalomyelitis eae mouse model multiple sclerosis ms,0.0
periventricular magnetisation transfer abnormalities early multiple sclerosis conclusion pvmtr gradients present earliest stage ms consistent pronounced microstructural wmdamage closer ventricles positive association reduced cmt lower mtr pvnawm suggests common pathophysiologic mechanism together findings indicate potential use multimodal mri refined marker msrelated tissue changes,0.0
impact antiinfective screening monitoring protocol together infectious disease consultation preventing infective adverse events patients treated anticd20 cd52 agents multiple sclerosis conclusions risk mitigation program including infectious disease consultation standardized screening prophylactic protocols effective reducing infective adverse events patients receiving anti cd20 cd52 agents ms,0.0
serum neurofilament light chain levels predict longterm disability progression patients progressive multiple sclerosis conclusions snfl can considered prognostic biomarker future longterm disability progression patients progressive ms data expand little knowledge existing role snfl longterm prognostic biomarker patients progressive ms,0.0
nuclear pore complexes doorway neural injury neurodegeneration genetic underpinnings endstage pathological hallmarks neurodegenerative diseases increasingly well defined cellular pathophysiology disease initiation propagation remains poorly understood especially sporadic forms diseases altered nucleocytoplasmic transport emerging prominent pathomechanism multiple neurodegenerative diseases including amyotrophic lateral sclerosis alzheimer disease frontotemporal dementia huntington disease,0.0
yoga provision individuals living multiple sclerosis future online conclusions homebased yoga practice viable enjoyable option individuals living ms recommended yoga studios offering homebased yoga provision consider individual differences preference well fluctuations symptoms may create inequitable access services may prevent participation,0.0
vitamin d calcium multiple sclerosis abstract,0.0
cost associated relapsefree patient multiple sclerosis realworld health indicator conclusions treatment cost per year achieve relapsefree patient stable successive measurements population therefore may considered good realworld health indicator patients rrms treated dmts,0.0
effects teriflunomide treatment cognitive performance brain volume patients relapsing multiple sclerosis post hoc analysis temso core extension studies conclusion teriflunomide improves cognition largely effects bvl accelerated bvl earlier disease course may predict cognitive outcomes,0.0
interdisciplinary approach opportunistic infections staphylococcal meningitis patient multiple sclerosis treatment dimethyl fumarate abstract,0.0
18f fdg brain pet clinical symptoms different autoantibodies autoimmune encephalitis systematic review conclusion results indicate huge diversity metabolic patterns among different ae subtypes hard draw firm conclusion moreover timing imaging seizures acute treatments can alter pet patterns strongly prospective investigations specific inclusion exclusion criteria carried identify metabolic defect different ae subtypes,0.0
research progress association neurological disorders periodontal diseases periodontal diseases inflammatory diseases caused oral pathogens around periodontal supporting tissues leading systemic chronic inflammatory conditions continuous chronic systemic inflammation may trigger neuroinflammation prominent feature variety neurological disorders implies may causal link periodontal diseases neurological disorders article presents epidemiological biological evidences,0.0
genetic biomarkers multiple sclerosis umbrella review metaanalyses observational studies abstractbackgroundmultiple sclerosis ms multifactorial nature genetic environmental factors contributing disease risk umbrella review aimed summarize various nonhla genes investigated association ms risk metaanalyses mas observational studiesmethodsmedline embase epistemonikos cochrane database systematic reviews searched mas july 2021 evidence association ranked according established criteria follows convincing highly suggestive suggestive weak significantresultsfrom 1 533 publications 85 fulltext articles evaluated eligibility 15 articles selected described 114 genetic associations associations supported convincing evidence one association rs2104286 vs g contrast polymorphism interleukin 2ra il2ra gene increased ms susceptibility initially supported highly suggestive evidence 117 95 ci 110125 downgraded suggestive sensitivity subgroup analyses also found six associations supported suggestive evidence main analysisconclusionthe findings study imply cytokines genes interleukin il2ra il7r may play role development ms data betterdesigned studies needed establish robust evidence,0.0
genetic biomarkers multiple sclerosis umbrella review metaanalyses observational studies abstractbackground multiple sclerosis ms multifactorial nature genetic environmental factors contributing disease risk umbrella review aimed summarize various nonhla genes investigated association ms risk metaanalyses mas observational studiesmethods medline embase epistemonikos cochrane database systematic reviews searched mas july 2021 evidence association ranked according established criteria follows convincing highly suggestive suggestive weak significantresults 1 533 publications 85 fulltext articles evaluated eligibility 15 articles selected described 114 genetic associations associations supported convincing evidence one association rs2104286 vs g contrast polymorphism interleukin 2ra il2ra gene increased ms susceptibility initially supported highly suggestive evidence 117 95 ci 110125 downgraded suggestive sensitivity subgroup analyses also found six associations supported suggestive evidence main analysisconclusion findings study imply cytokines genes interleukin il2ra il7r may play role development ms data betterdesigned studies needed establish robust evidence,0.0
shift multiple sclerosis onset towards older age conclusion study shows forward shift towards older age onset ms thus suggesting considerable thought placeintherapy currently used diseasemodifying treatments standard care older population,0.0
multiple sclerosis biomarker candidates revealed celltypespecific interactome analysis multiple sclerosis ms demyelinating disorder affects multiple regions central nervous system brain spinal cord optic nerves susceptibility ms well disease progression rates displays marked patienttopatient variability date biomarkers forecast differences clinical phenotypes outcomes limited context celltypespecific interactome analyses offer important prospects hope novel diagnostics,1.0
contactdependent granzyme bmediated cytotoxicity th17polarized cells toward human oligodendrocytes multiple sclerosis ms characterized loss myelin myelinproducing oligodendrocytes ols central nervous system cns proinflammatory cd4 + th17 cells considered pathogenic ms harmful ols investigated mechanisms driving human cd4 + t cellmediated ol cell death using fluorescent brightfield vitro live imaging found compared th2polarized cells th17polarized cells show greater interactions primary human ols,1.0
prevalence depression anxiety among adult patients multiple sclerosis riyadh city saudi arabia conclusion depression frequent anxiety result assessing psychiatric diseases study group depression anxiety may expected frequent amongst greater disability,0.0
active videogaming interventions adults neuromuscular conditions scoping review review synthesized active videogaming avg intervention literature 10year period 20102020 people neuromuscular conditions 1864 years age examining interventions aimed improve health secondary conditions physical activity outcomes quality life qol systematic searches yielded 40 eligible studies major groups multiple sclerosis 40 stroke 33 study participants mostly mildtomoderate disability able,0.0
tissue donations multiple sclerosis research current state suggestions improvement although major progress multiple sclerosis research made last decades key questions related cause mechanisms brain spinal cord pathology remain unresolved cover broad range topics including disease aetiology antigenic triggers immune response inside outside cns mechanisms inflammation demyelination neurodegeneration tissue repair questions can addressed novel molecular technologies,1.0
objectively assessed physiological physical cognitive function along patientreported outcomes first 2 years alemtuzumab treatment multiple sclerosis prospective observational study conclusion present findings suggest alemtuzumab treatment relapsingremitting pwms can improve certain domains physical function short distance walking cognitive function processing speed memory furthermore stabilize physiological physical function along patientreported outcomes,0.0
engineered nanoerythrocyte alleviate central nervous system inflammation regulating polarization inflammatory microglia microglial polarization one promising therapeutic strategies multiple central nervous system cns disorders however safe effective controllable microglial regulation still faces formidable challenges although antiinflammatory factors promote microglia polarization short halflife high cost unpredictable vivo behavior complex delivery operations hamper clinical application inspired natural microhemorrhage cleaning mechanism,1.0
clinical advances rna therapeutics treatment neurological neuromuscular diseases rna therapeutics comprise diverse group oligonucleotidebased drugs antisense oligonucleotides asos small interfering rnas sirnas short hairpin rnas shrnas can designed selectively interact drug targets currently undruggable small moleculebased drugs monoclonal antibodies furthermore rnabased therapeutics potential modulate entire disease pathways thereby represent new modality unprecedented potential generating,1.0
multiple sclerosis cancer diagnosis diagnostic route cancer stage diagnostic interval breast colorectal cancer conclusion breast cancers less likely detected screening colorectal cancer likely detected early stage people ms without ms msrelated disability may prevent people getting mammograms colonoscopies understanding pathways earlier detection cancers critical developing planning interventions ameliorate outcomes people ms cancer,0.0
tuberous sclerosis complex complex case tuberous sclerosis complex tsc inheritable disorder characterized formation benign yet disorganized tumors multiple organ systems germline mutations tsc1 hamartin frequently tsc2 tuberin genes causative tsc malignant manifestations tsc pulmonary lymphangioleiomyomatosis lam renal angiomyolipoma aml may also occur independent sporadic perivascular epithelial cell tumor pecoma characterized somatic tsc2 mutations thus,0.0
longterm immunological consequences anticd20 therapies humoral responses covid19 vaccines multiple sclerosis observational study conclusion anticd20induced inhibition humoral responses covid19 vaccines transient antibody production pronounced 18 months anticd20 treatment discontinuation immunological effect bcell counts appears wane time,0.0
th17 pathway vascular inflammation culprit consort involvement il17a autoimmune inflammatory diseases prompted development therapeutic strategies block th17 pathway promising results came use psoriasis ankylosing spondylitis il17a acts various cell types local systemic effects considering premature mortality observed chronic inflammatory diseases il17a action vascular cells studied vitro vivo results suggest cytokine favors,0.0
sleeprelated breathing disorders multiple sclerosis prevalence features associated factors conclusion study provide evidence association msspecific symptoms fatigue sleepiness depression central obstructive apneas even presence brainstem lesions,0.0
intellectual structure emerging trends white matter hyperintensity studies bibliometric analysis 2012 2021 white matter hyperintensities wmhs significant effect human health received increasing attention since number publications increased past 10 years aimed explore intellectual structure hotspots emerging trends publications wmhs using bibliometric analysis 2012 2021 publications wmhs 2012 2021 retrieved web science core collection citespace 58r3 vosviewer 1617 online bibliometric,0.0
cancer screening patients multiple sclerosis enough abstract,0.0
multiple sclerosis incidence black patients time away racial medical myth abstract,0.0
association obesity different age periods multiple sclerosis saudi arabia multicenter casecontrol study conclusion overweight obesity intermediate school period ages 1315 years associated increased risk ms particularly among females,0.0
efficacy safety rituximab patients multiple sclerosis observational study tertiary center makkah saudi arabia conclusion rituximab efficient drug reducing annual relapse rate mri activity patients ms tolerable side effects leading drug discontinuation lethal outcome,0.0
multimodal biomarkers repetitive head impacts traumatic encephalopathy syndrome clinicopathological case series traumatic encephalopathy syndrome tes criteria developed aid diagnosis chronic traumatic encephalopathy cte pathology life interpreting clinical biomarker findings patients tes life requires autopsybased determination neuropathological profile report clinicopathological series 9 patients prior repetitive head impacts rhi classified retrospectively using tes research framework 100 male white caucasian age death,0.0
factors associated oral fingolimod use injectable disease modifying agent use multiple sclerosis conclusions initial years market approval patients highly active ms likely receive oral fingolimod injectable dmas research needed understand determinants newer oral dmas,0.0
role multidisciplinary health care team management patients systemic sclerosis systemic sclerosis ssc rare connective tissue disease characterised immune dysfunction vascular damage fibrosis affecting skin multiple internal organs clinical spectrum ssc wide manifestations may lead severe morbidity mortality addition great impact patients quality life due multifaceted clinical manifestations ssc management requires combined expertise different medical specialists guarantee adequate,0.0
socioeconomic impact multiple sclerosis france results petals study conclusions ms imposes substantial cost burden french society approximately half total annual costs driven indirect costs,0.0
multiple sclerosis progressive courses clinical cohort longterm disability progression study conclusions study provides estimates annual disability progression edss changes ppms spms estimates useful tool healthcare decision makers clinicians properly assess impact clinical interventions,0.0
racial ethnic disparities multiple sclerosis prevalence conclusions ms prevalence varies race ethnicity similarly high white black significantly lower hispanic asian persons southern california taken together previous studies findings indicate burden ms us black community long underrecognized studies needed determine whether ms emerging disease among us hispanic adults whether ms susceptibility prevalence vary among hispanic asian individuals,0.0
followup retinal thickness optic mri optic neuritis antimog antibodyassociated disease antiaqp4 antibodypositive nmosd conclusions progression retinal atrophy chronic phase observed patients aqp4abpositive nmosd remains uncertain patients mogad visual impairments upon similar levels retinal atrophy worse aqp4abpositive nmosd possibly attributable part higher incidence optic nerve atrophy disease,0.0
quality life pediatriconset multiple sclerosis different disease course different impact different measurement approach needed abstractobjectiveto understand impact pediatric multiple sclerosis ms healthrelated quality life hrql measures used however specific areas concern youths ms known objective study contribute content inclusion new conditionspecific measure life impact ms children adolescentsmethodsa patient engagement framework used online survey developed using patient generated index pgi text threads generated pgi mapped international classification functioning disability health icf comprehensive icf core set msresultsa total 20 people completed pgi survey 11 youths ms aged 14 22 years 75 areas nominated youths ms related activities participation approximately 20 related body function contrast 60 areas nominated parents related body function finding indicated measure life impact need include impairments associated ms important activities roles new approach disability component covers msrelated impairments completed using pgi system youth select disability areas affected ms rate prioritize area improvement quality life component queries areas going wellconclusionthis new measurement approach prove useful overcoming challenges developing conditionspecific measures rare conditions,0.0
quality life pediatriconset multiple sclerosis different disease course different impact different measurement approach needed abstractobjectiveto understand impact pediatric multiple sclerosis ms healthrelated quality life hrql measures used however specific areas concern youths ms known objective study contribute content inclusion new conditionspecific measure life impact ms children adolescentsmethodsa patient engagement framework used online survey developed using patient generated index pgi text threads generated pgi mapped international classification functioning disability health icf comprehensive icf core set msresultsa total 20 people completed pgi survey 11 youths ms aged 14 22 years 75 areas nominated youths ms related activities participation approximately 20 related body function contrast 60 areas nominated parents related body function finding indicated measure life impact need include impairments associated ms important activities roles new approach disability component covers msrelated impairments completed using pgi system youth select disability areas affected ms rate prioritize area improvement quality life component queries areas going wellconclusionthis new measurement approach prove useful overcoming challenges developing conditionspecific measures rare conditions,0.0
digital selfmonitoring multiple sclerosis interview study dutch health care providers expected new configuration roles responsibilities conclusions findings show health care providers envisage particular type patient empowerment personalized health care tensions arise health care providers acting gatekeepers patient autonomy patient empowerment patient disempowerment weight given quantitative objective data given patients subjective experiences future research interesting investigate actual experiences health,0.0
alemtuzumab induced hemodynamic change relapsing multiple sclerosis occurs independent corticosteroid premedication retrospective multicentre study background alemtuzumab atz highly effective disease modifying treatment relapsing multiple sclerosis ms associated rare risk intracerebral hemorrhage increase blood pressure bp hypothesized causative prior administration highdose methylprednisolone hdmp potential confounder objective analyze bp change ms patients treated atz prior hdmp treatment compared patients receiving hdmp acute relapse methods,0.0
seroconversion antiaquaporin4 antibody patient neuromyelitis optica spectrum disorder case report report case patient neuromyelitis optica spectrum disorder nmosd originally treated multiple sclerosis ms due negative antiaquaporin4 aqp4 antibody test later antibody titer became positive 58yearold woman without prior medical history developed acute left facial pain vomiting hiccups mri showed intraparenchymal lesion extending medulla oblongata cervical cord high t 2 weighted signal intensity patient,0.0
association evidence disease activity longterm disability progression multiple sclerosis systematic review metaanalysis conclusions neda3 associated longterm disability progression rrms low high efficacy therapies studies early composite outcome measures incorporating easily measurable biomarkers longer followup may help improve prognostic value neda3 rrms,0.0
general vaccination willingness current vaccination status relation clinical psychological variables patients multiple sclerosis conclusions specific personality trait defined relation general vaccination willingness complete vaccination status younger patients made aware influenza vaccination reasons rather low vaccination rates need investigated,0.0
corpus callosum damage account cognitive affective socialcognitive dysfunctions multiple sclerosis model callosal disconnection syndrome corpus callosum cc major commissure interconnecting two hemispheres particularly affected multiple sclerosis ms present review aimed investigate role played callosal damages pathogenesis msrelated dysfunctions examine whether model callosal disconnection syndrome valid model ms purpose will first review structural functional evidence callosal pathology ms second will account,0.0
antisarscov2 monoclonal antibodies treatment active covid19 multiple sclerosis observational study monoclonal antibodies mabs severe acute respiratory syndrome coronavirus 2 sarscov2 received emergency use authorization acute treatment covid19 aware published data use immunosuppressed people multiple sclerosis pwms report 23 pwms mean age 49 years ocrelizumab n 19 fingolimod n 2 vaccinated least initial series n 19 received mab acute covid19 following mab receipt approximately half,0.0
virusspecific antibody indices may supplement total igg index diagnostics multiple sclerosis intrathecal antibody synthesis viruses associated multiple sclerosis ms igg levels epsteinbarr virus ebv bamhia rightward frame 1 barf1 ebv nuclear antigen 1 ebna1 mumps virus muv nucleoprotein nup measles virus mev nup rubella virus ruv capsid protein cap found elevated serum cerebrospinal fluid csf ms patients compared healthy controls hcs whereas opposite found cytomegalovirus cmv pp52 strong,0.0
association parental mental illness autoimmune diseases offspring nationwide registerbased cohort study sweden mental illness previously linked autoimmune diseases yet associations parental mental illness offsprings risk autoimmune diseases largely unknown conducted populationbased cohort study 2 192 490 swedish children born 1991 2011 parents determine associations parental mental illness risk autoimmune diseases among offspring timedependent diagnoses parental mental illness psychosis alcohol drug,0.0
humoral cellular response sarscov2 vaccine modified dmt patients multiple sclerosis autoimmune diseases conclusion anticd20s s1prm modify immunological responses sarscov2 vaccines,0.0
lower cerebral arterial blood flow associated greater serum neurofilament light chain levels multiple sclerosis patients conclusion lower cabf associated increased snfl ms patients highlighting relationship cerebral hypoperfusion axonal pathology,0.0
toward identification personalized immunological profiles multiple sclerosis diversity four previously unidentified autoantigens found multiple sclerosis mirrors notorious clinical variability,0.0
multiple sclerosis immunopathological heterogeneity implications multiple sclerosis ms common autoimmune demyelinating disease central nervous system cns past decades several immunomodulatory disease modifying treatments multiple presumed mechanisms action developed ms remains incurable disease whereas high efficacy least early disease corroborates underlying immunopathophysiology profound heterogeneity clinical presentation well immunophenotypes may also vary,1.0
identification four novel t cell autoantigens personal autoreactive profiles multiple sclerosis multiple sclerosis ms inflammatory disease central nervous system cns pathological t cells likely autoimmune play key role despite central importance autoantigen repertoire remains largely uncharacterized using novel vitro antigen delivery method combined human protein atlas library screened t cell autoreactivity 63 cnsexpressed proteins identified four previously unreported autoantigens ms fatty acidbinding,0.0
association traumatic brain injury without loss consciousness neuropathologic outcomes communitydwelling older persons conclusions relevance crosssectional analysis suggests history tbi even without loc associated agerelated neuropathologic outcomes neurodegenerative vascular variation neuropathologic outcomes individuals without loc may provide clues potential mechanisms diagnoses management persons tbi,0.0
pure relapsing short myelitis part multiple sclerosis spectrum new entity background objectives pure relapsing short myelitis clinical paraclinical features suggesting multiple sclerosis ms described recently evaluated existence potential new form ms retrospectively searching similar cases databases french tertiary ms centers,0.0
para postcovid19 cns acute demyelinating disorders children case series expanding spectrum clinical radiological characteristics viral infections can serve trigger variable autoimmune antibodymediated demyelinating disorders accumulating evidence severe acute respiratory syndrome coronavirus 2 sarscov2 virus causing coronavirus disease 2019 covid19 infection responsible current worldwide pandemic can lead cascade immunemediated brain spinal cord demyelinating injuries however observation pediatric age group reported,0.0
comparison multicenter mri protocols visualizing spinal cord gray matter conclusion propose quality assessment criteria metrics graymatter visualization apply different protocols proposed criteria metrics analyzed protocols opensource code can serve benchmark future optimization spinal cord graymatter imaging protocols,0.0
disproportional increase psoriasis reports association b cell depleting therapies patients multiple sclerosis abstractbackgroundsome pathways involved pathogenesis psoriasis share similarities processes involved multiple sclerosis ms pathogenesis however association ms psoriasis poorly understood since diseasemodifying therapies ms various targets may possible occurrence psoriasis varies drugobjectiveto analyze frequency psoriasis reports patients treated various diseasemodifying therapies msmethodsdata collected using fda adverse event reporting system faers openfda database january 2009 june 2020 study analyzed total reports psoriasis total reports skin subcutaneous tissue disorders category drug explored age sex distribution report source openfda data used perform statistical analyses including reporting odds ratios ror information componentsresultsthe study identified 517 psoriasis reports 45 547 total skin subcutaneous tissue disorders 113 faers highest proportions reports study associated rituximab ocrelizumab interferon beta 1a lowest proportion reports associated glatiramer acetate alemtuzumab dimethyl fumarate teriflunomide reports autoimmune skin disorders minimal 29 vitiligo 33 pemphigoid 7 pemphigus patients primarily drove reports dmts versus healthcare providers proportion reports female patients highest dmt except alemtuzumab openfda query retrieved 302 total reports psoriasis significantly increased reporting odds ratios rors 95 confidence interval psoriasis noted rituximab 714 3921300 ocrelizumab 379 274523 fingolimod 133 101176 significantly decreased rors noted natalizumab 053 036080 glatiramer acetate 058 035096 dimethyl fumarate 071 053094 conclusionthere frequent reports psoriasis ms patients treated various dmts however reports rors disproportionally high association b cell depleting therapies research required determine certain dmts may serve better options individuals affected highrisk developing psoriasis,0.0
disproportional increase psoriasis reports association b cell depleting therapies patients multiple sclerosis abstractbackgroundsome pathways involved pathogenesis psoriasis share similarities processes involved multiple sclerosis ms pathogenesis however association ms psoriasis poorly understood since diseasemodifying therapies ms various targets may possible occurrence psoriasis varies drugobjectiveto analyze frequency psoriasis reports patients treated various diseasemodifying therapies msmethodsdata collected using fda adverse event reporting system faers openfda database january 2009 june 2020 study analyzed total reports psoriasis total reports skin subcutaneous tissue disorders category drug explored age sex distribution report source openfda data used perform statistical analyses including reporting odds ratios ror information componentsresultsthe study identified 517 psoriasis reports 45 547 total skin subcutaneous tissue disorders 113 faers highest proportions reports study associated rituximab ocrelizumab interferon beta 1a lowest proportion reports associated glatiramer acetate alemtuzumab dimethyl fumarate teriflunomide reports autoimmune skin disorders minimal 29 vitiligo 33 pemphigoid 7 pemphigus patients primarily drove reports dmts versus healthcare providers proportion reports female patients highest dmt except alemtuzumab openfda query retrieved 302 total reports psoriasis significantly increased reporting odds ratios rors 95 confidence interval psoriasis noted rituximab 714 3921300 ocrelizumab 379 274523 fingolimod 133 101176 significantly decreased rors noted natalizumab 053 036080 glatiramer acetate 058 035096 dimethyl fumarate 071 053094 conclusionthere frequent reports psoriasis ms patients treated various dmts however reports rors disproportionally high association b cell depleting therapies research required determine certain dmts may serve better options individuals affected highrisk developing psoriasis,0.0
opportunities molecular imaging multiple sclerosis management linking probe treatment imaging critical component multiple sclerosis ms management nearly 40 years visual information derived structural mri signs bloodbrain barrier disruption inflammation demyelination brain spinal cord atrophy primary metrics used evaluate therapeutic efficacy ms development targeted imaging probes expanded ability evaluate monitor ms therapies molecular level molecular imaging,1.0
auxilin novel susceptibility gene congenital heart block directly impacts fetal heart function conclusions study identifies auxilin first genetic susceptibility factor nle modulating cardiac function opening new avenues development screening therapeutic strategies chb,0.0
relationship subjective report objective assessment neurocognitive functioning persons multiple sclerosis conclusions results suggest msnqself msnqinformant show similar utility findings also suggest domains executive function memory may salient thus reflected subjective reports cognitive functioning future work examine impact mood disturbance cognitive performance iiv,0.0
validation pediatric idiopathic generalized epilepsy diagnoses danish national patient register 19942019 conclusion danish national patient register danish prescription database suitable identifying children ige subtypes except juvenile myoclonic epilepsy can identified caution,0.0
microstructural changes normal appearance cerebral cortex multiple sclerosis detected advanced diffusion mri technique abstract,0.0
imaging subtle leaks bloodbrain barrier aging human brain potential pitfalls challenges possible solutions recent studies using dynamic contrastenhanced magnetic resonance imaging dcemri gadoliniumbased contrast agents gbca demonstrated subtle bloodbrain barrier bbb leaks human brain normal aging individuals agerelated cognitive dysfunction genetic risk alzheimers disease ad mild cognitive impairment early ad cerebral small vessel disease svd neurodegenerative disorders neurological conditions bbb leaks quantified,0.0
tolerability feasibility athome remotely supervised transcranial direct current stimulation rstdcs singlecenter evidence 6 779 sessions conclusions athome rstdcs tolerable including used extended periods time homebased rstdcs feasible can enable class tdcs clinical trial designs,0.0
advancing care outcomes african american patients multiple sclerosis multiple sclerosis ms historically underdiagnosed undertreated among african americans recent evidence suggests african americans ms different clinical presentation increased disease incidence burden worsened longterm outcomes versus white counterparts due limited data available african americans ms clinical trials difficult make informed generalizable conclusions natural history prognosis therapeutic,0.0
neurological manifestations covid19 potential gate determinants poor prognosis conclusion covid19 neurologic complications key drivers patient severity mortality headache convulsions mental psychic disorders delirium insomnia just symptoms virus can cause olfactory nerve commonly damaged cranial nerve resulting anosmia stroke mostly infarction encephalitis meningitis guillainbarre syndrome relapse multiple sclerosis transverse myelitis symptoms squeals,0.0
radiosynthesis characterization carbon11 pet tracer receptorinteracting protein kinase 1 introduction receptorinteracting protein kinase 1 ripk1 emerged crucial regulator necroptosis inflammatory response activating group downstream immune receptors recognized pivotal contributor cell death inflammation various physiological pathological processes ripk1 deficiency dysregulation humans can cause severe immunodeficiency neurodegenerative diseases multiple sclerosis amyotrophic lateral sclerosis,0.0
medicalization exercise vigilance productivity selfcare secondary data analysis qualitative interviews among multiple sclerosis exercise becoming integrated management multiple sclerosis ms promoted manage impairments symptoms whereas extensive research outlines factors impacting participation less known regarding medicalized exercise promotion might impact views exercise self conducted secondary data analysis understand medicalized exercisepromotion paradigms impact meaning roles exercise among ms twentytwo interviews selected,0.0
autoimmune encephalitis associated covid19 systematic review conclusion systematic review revealed evidence ae development patients infected covid19 clinicians aware possible diagnosis ae considering neurological differential diagnosis sarscov2 infected patients,0.0
natalizumab therapy patients pediatriconset multiple sclerosis greece clinical immunological insights timelong administration future directionsa singlecenter retrospective observational study pediatriconset multiple sclerosis ms poms accounts 35 ms cases characterized highly inflammatory profile often warranting treatment highefficacy agents aim present realworld data series 18 hellenic poms patients treated natalizumab ntz either adolescents adults high disease activity efficiently subsided clinical imaging laboratory data 18 poms patients received least one ntz infusion,0.0
potential roles amino acids major derivatives management multiple sclerosis recently reviewed important role carbohydrates lipids metabolism different clinical aspects multiple sclerosis ms disease current paper aimed review contribution amino acids major derivatives different clinical outcomes disease including etiology pathogenesis diagnosis prognosis treatment line thr threonine phe phenylalanine glu glutamate trp tryptophan sero serotonin main examples,0.0
recurrent intracerebral hemorrhage due alemtuzumab treatment patient multiple sclerosis case report abstract,0.0
reliability validity 30second chair stand test modified four square step test persons multiple sclerosis conclusion 30scst mfsst valid reliable mildlydisabled individuals ms,0.0
multiple sclerosis patients altered gut mycobiome increased fungal bacterial richness trillions microbes bacteria fungi viruses exist healthy human gut microbiome although gut bacterial dysbiosis extensively studied multiple sclerosis ms significance fungal microbiome mycobiome understudied neglected part intestinal microbiome ms aim study characterize gut mycobiome patients relapsingremitting multiple sclerosis rrms compare healthy controls examine,0.0
atopic dermatitis risk autoimmune conditions populationbased cohort study conclusion people ad increased risk multiple autoimmune conditions especially severe ad,0.0
memory polish multiple sclerosis patients correlations mood fatigue conclusions memory impairment occurs patients ms affects employment status depressive symptoms anxiety fatigue unlike neurological status directly related memory status,0.0
moderatetovigorous physical activity associated processing speed learning memory cognitively impaired persons multiple sclerosis abstractbackgroundphysical activity pa measured steps day correlates cognition persons msobjectivesthe current study extended previous research examining association devicemeasured pa cognitive outcomes based neuropsychological testing among persons ms prescreened cognitive impairmentmethodsthe sample included 60 persons ms underwent cognitive performance tests sdmt cvltii bvmtr wore accelerometer elastic waist band waking hours 7day period measuring pa across activity spectrum sedentary behavior light pa lpa moderatetovigorous pa mvpa data analyzed bivariate partial spearman rankorder correlations using spssresultsmvpa statistically significant correlations sdmt cvltii bvmtr lpa statistically significant correlation sdmt cvltii bvmtr sedentary behavior demonstrate statistically significant correlations cognitive outcomes mvpa statistically significant correlations sdmt controlling age sex education disability status correlations statistically significant controlling covariatesconclusionthis initial crosssectional data supports design pa interventions target ambulatory pa form mvpa managing msrelated cps impairment ms,0.0
moderatetovigorous physical activity associated processing speed learning memory cognitively impaired persons multiple sclerosis abstractbackgroundphysical activity pa measured steps day correlates cognition persons msobjectivesthe current study extended previous research examining association devicemeasured pa cognitive outcomes based neuropsychological testing among persons ms prescreened cognitive impairmentmethodsthe sample included 60 persons ms underwent cognitive performance tests sdmt cvltii bvmtr wore accelerometer elastic waist band waking hours 7day period measuring pa across activity spectrum sedentary behavior light pa lpa moderatetovigorous pa mvpa data analyzed bivariate partial spearman rankorder correlations using spssresultsmvpa statistically significant correlations sdmt cvltii bvmtr lpa statistically significant correlation sdmt cvltii bvmtr sedentary behavior demonstrate statistically significant correlations cognitive outcomes mvpa statistically significant correlations sdmt controlling age sex education disability status correlations statistically significant controlling covariatesconclusionthis initial crosssectional data supports design pa interventions target ambulatory pa form mvpa managing msrelated cps impairment ms,0.0
motherhood choice multiple sclerosis moms development piloting patientreported outcome measures abstractbackgroundmultiple sclerosis ms particularly affects women age 20 40 therefore pregnancy often important issue women ms wwms misunderstandings misinformation uncertainties ms pregnancy common developed pilottested two questionnaires one knowledge mckq one attitudes coping strategies worries mpwq wwms regarding pregnancymethodsthis mixedmethods study followed mrc framework development evaluation complex interventions two questionnaires developed based earlier questionnaire qualitative study cognitively debriefed pilot tested webbased survey qualitative data analysed using thematic analysis psychometric analysis included item difficulty reliability questionnaires convergent validity assessment exploratory factor analysis efa mpwq resultsthe qualitative study three focus groups interviews 15 wwms overall interviews 4 experts revealed several topics requiring evidencebased decision support multidisciplinary panel produced 16item mckq 39item mpwq cognitive debriefing questionnaires went smoothly 128 wwms approached survey 95 74 completed mckq 89 70 mpwq mean age wwms 367 years 88 relapsing ms 32 children item difficulty reliability convergent validity acceptable questionnaires efa confirm threescale structure attitude worries coping conclusionthe developed questionnaires fill gap selfreported measures knowledge mckq attitudes worries coping strategies mpwq wwms regarding motherhood refinement mpwq validation larger sample warranted largescale use,0.0
motherhood choice multiple sclerosis moms development piloting patientreported outcome measures abstractbackgroundmultiple sclerosis ms particularly affects women age 20 40 therefore pregnancy often important issue women ms wwms misunderstandings misinformation uncertainties ms pregnancy common developed pilottested two questionnaires one knowledge mckq one attitudes coping strategies worries mpwq wwms regarding pregnancymethodsthis mixedmethods study followed mrc framework development evaluation complex interventions two questionnaires developed based earlier questionnaire qualitative study cognitively debriefed pilot tested webbased survey qualitative data analysed using thematic analysis psychometric analysis included item difficulty reliability questionnaires convergent validity assessment exploratory factor analysis efa mpwq resultsthe qualitative study three focus groups interviews 15 wwms overall interviews 4 experts revealed several topics requiring evidencebased decision support multidisciplinary panel produced 16item mckq 39item mpwq cognitive debriefing questionnaires went smoothly 128 wwms approached survey 95 74 completed mckq 89 70 mpwq mean age wwms 367 years 88 relapsing ms 32 children item difficulty reliability convergent validity acceptable questionnaires efa confirm threescale structure attitude worries coping conclusionthe developed questionnaires fill gap selfreported measures knowledge mckq attitudes worries coping strategies mpwq wwms regarding motherhood refinement mpwq validation larger sample warranted largescale use,0.0
neurosurgical mimics goal following article help practicing physician learn recognize conditions mimic conditions requiring neurosurgical intervention case vignette presented relevant clinical history examination imaging studies findings well testing results management corresponding diagnosis presented finally relevant mimics differentiating features discussed,0.0
assessment computer assisted rehabilitation environment caren system use mood patients multiple sclerosis conclusions current research evaluating rehabilitation patients ms using caren system scarce pilot study important inform prospective studies exploring use caren system psychological rehabilitation patients 5 caren sessions lower baseline phq9 scores may suggest mood plays role selection patients caren system use study shows mood affected caren system specific research needs,0.0
depletion b7h4 c3h10 t1 2 mesenchymal stem cells attenuates immunomodulatory therapy experimental autoimmune encephalomyelitis mice considering controversial issue whether msc therapy effective treatment multiple sclerosis important seek powerful data clarify effect mscs b7h4 unique costimulatory molecule belongs b7 ligand family broadly expressed lymphoid nonlymphoid tissues previous studies shown b7h4 involved regulating progression autoimmune diseases however role mscs stem cell transplantation remains,1.0
moderating roles selfefficacy depression dualtask walking multiple sclerosis test selfawareness theory conclusions findings indicate interplay physical ability psychological factors like depression fse may enhance understanding walking performance complex realworld dtw contexts,0.0
slowing processing speed associated cognitive fatigue newly diagnosed multiple sclerosis patients conclusions cf can detected even newly diagnosed pwms might objectively manifest progressive increase omissions sustained highly demanding task ie pasat pattern may reflect slowed processing speed increased fatigue pwms focusing omissions pasat instead correct responses may improve specificity objective measure cf,0.0
natural killer cells multiple sclerosis entering stage studies investigating immunopathology multiple sclerosis ms largely focused adaptive t b lymphocytes however recent years increased interest contribution innate immune cells amongst natural killer nk cells apart canonical role controlling viral infections cell stress malignancies nk cells increasingly recognized modulating effect adaptive immune system health autoimmune,0.0
effects 6min treadmill walking test dualtask gait performance prefrontal hemodynamics people multiple sclerosis fatigue one limiting symptoms people multiple sclerosis pwms can subdivided trait state fatigue activityinduced state fatigue describes temporary decline motor cognitive performance motor cognitive performance fatigability respectively increase perception fatigue perceived fatigability response motor cognitive tasks best knowledge effects 6min walk test 6mwt,0.0
sexbased differences oxygen cost walking energy equivalents minimally disabled individuals multiple sclerosis controls conclusions metabolic demands elevated walking minimally disabled individuals rrms furthermore higher energy demands occur men probably due increased step symmetry base support clinicians advised follow energy expenditure metrics collected walking can indicate decrease fitness even early phase ms,0.0
current evidence potential therapeutic applications transcranial magnetic stimulation multiple sclerosis systematic review literature conclusions excitatory electromagnetic pulses applied affected cerebral hemisphere allow us optimise functional brain activity including transmission nerve impulses demyelinated corticospinal pathway various studies tms safely shown statistically significant improvements spasticity fatigue lower urinary tract dysfunction manual dexterity gait cognitive deficits related working memory patients ms however exact level,1.0
bu shen yi sui capsules promote remyelination regulating microrna219 microrna338 exosomes promote oligodendrocyte precursor cell differentiation remyelination refractory feature demyelinating diseases multiple sclerosis ms studies shown promoting oligodendrocyte precursor cell opc differentiation achieved currently available therapeutic agents key enhancing remyelination bu shen yi sui capsule bsysc traditional chinese herbal medicine many years clinical practice found bsysc can effectively treat ms study effects bsysc,1.0
degenerative spine disorders multiple sclerosis multiple sclerosis ms autoimmune inflammatory disease results demyelination central nervous system cns ms affects many 350 000 individuals united states commonly presents age 45 years patients ms general population likely encounter degenerative changes spine age can pose unique challenge patients ms physicians conditions can great deal symptomatic overlap,1.0
sittostand transition biomarker impairment comparison instrumented 30second chair stand test daily life transitions multiple sclerosis falls mobility deficits common people multiple sclerosis pwms across levels clinical disability however functional mobility observed supervised settings may reflect daily life may impact assessments fall risk impairment clinic investigate compared utility sensorbased performance metrics sitstand transitions daily life structured task inform fall risk impairment pwms thirtyseven pwms,0.0
qualitative study health care professionals views bowel care multiple sclerosis whose job anyway conclusions hcps caring individuals ms see many bowel dysfunction variation care service provision hcps require education evidencebased clinical guidelines referral pathways improve case finding assessment management symptoms individuals ms,0.0
preliminary support behavioral intervention trait conscientiousness multiple sclerosis conclusions results support hypothesis behaviors typically associated low conscientiousness may addressed behavioral therapy ms population addition positive employment changes treatment group several quality life changes described study participants additional research needed,0.0
gut microbiota interact brain systemic chronic inflammation implications neuroinflammation neurodegeneration aging noticed recent years unfavorable effects gut microbiota exhaust host vigor life yet knowledge theory just beginning established increasing documentation suggests microbiotagutbrain axis impacts brain cognition psychiatric symptoms also precipitates neurodegenerative diseases alzheimers disease ad parkinsons disease pd multiple sclerosis ms bloodbrain barrier bbb machinery,0.0
isolation mouse primary microglia magneticactivated cell sorting animal models demyelination microglia resident innate immune cells brain primary responders inflammation injury central nervous system cns microglia can divided resting state activated state can rapidly change state response microenvironment brain microglia will activated different pathological conditions exhibit different phenotypes addition many different subgroups activated microglia great heterogeneity,1.0
characteristics prescription drug use among individuals multiple sclerosis us medicare population conclusions medicare beneficiaries ms using dmts face considerable outofpocket costs beneficiaries also used significant number medications potentially used msrelated symptoms although total outofpocket costs modest,0.0
oxygen cost walking people multiple sclerosis association fatigue systematic review metaanalysis conclusions individuals ms expend energy walking compared controls increase energy expenditure may contribute development fatigue studies found higher oxygen costs walking associated greater fatigue future studies investigate whether reducing energy expenditure movement improves fatigue,0.0
different impact gadopentetate gadobutrol inflammationpromoted retention toxicity gadolinium within mouse brain conclusions eae model neuroinflammation promoted increased gd retention brain gbcas whereas inflamed brains efficient clearance macrocyclic gadobutrol investigated time period observed gd retention application linear gadopentetate persisted entire observational period gadopentetate gadubutrol appeared neurotoxic ex vivo paradigm neuronal inflammation,0.0
immune cell contributors female sex bias multiple sclerosis experimental autoimmune encephalomyelitis multiple sclerosis ms chronic autoimmune demyelinating disease central nervous system cns leads axonal damage accumulation disability relapsingremitting ms rrms frequent presentation ms form ms three times prevalent females males female bias ms apparent puberty suggesting role sex hormones regulation however little known biological mechanisms underpin,1.0
recent advances acidsensitive ion channels central nervous system diseases acidsensitive ion channels asics cationic channels activated extracellular protons widely distributed nervous system mammals belongs enac deg family four coding genes asic1 asic2 asic3 asic4 encode eight subunit proteins asic1a asic1b asic1b2 asic2a asic2b asic3 asic4 asic5 different subtypes asics different distributions central nervous system play important role various physiological,0.0
covan leading eskd despite minimal covid symptoms report case dialysis dependence patient covid19associated nephropathy covan minimal respiratory manifestations 25yearold man history multiple sclerosis remission presented mild dyspnea due covid19 pneumonia found rapidly worsening kidney function required nasal cannula able weaned within days despite mild respiratory disease kidney function worsened urgent hemodialysis,0.0
multiple sclerosis treatment covid19 era riskbenefit approach covid19 pandemic poses ongoing global challenge several risk factors make people multiple sclerosis pwms particularly susceptible running severe disease course although literature report numerous articles risk factors severe covid19 vaccination response pwms scarcity reviews integrating aspects strategies aimed minimizing risks aim review describe risk vulnerable pwms exposed,0.0
multiple sclerosis lesions atrophy spinal cord distribution across vertebral levels correlation disability conclusion sc lesions atrophy already exist stage rrms whole sc accentuation cervical enlargement sc lesions atrophy pronounced stage pms contribute clinical picture largely independent,0.0
concomitant multiple sclerosis polycythemia vera successfully treated glatiramer acetate abstract,0.0
nutrition education programs adults neurological diseases lacking scoping review nutrition recommendation common neurological diseases follow national dietary guidelines mitigate malnutrition reduce risk dietrelated diseases help manage common symptoms including constipation nutrition education programs can support people adhering guidelines hence aim scoping review explore programs implemented adults neurological diseases conducted review according,0.0
cd40cd40l neurological disease immuneinflammatory conditions central nervous system cns rely molecular cellular interactions homeostatically maintained protect neural tissue harm cd40cd40l interaction upregulates key proinflammatory molecules function best understood context infection bcells activated via cd40 signaling produce antibodies however role cd40 neurological disease noninfectious etiology unclear review role,0.0
rankranklopg axis multiple sclerosis contribution placenta women multiple sclerosis ms can safely become pregnant give birth side effects impediments pregnancy generally accepted period wellbeing relapses softer evolution particularly third trimester herein hypothesized placenta via secretome contribute recognized beneficial effects pregnancy ms activity focused wellknown receptor ligand decoy receptor system one composed,0.0
safety data patients autoimmune diseases treatment high doses vitamin d3 according coimbra protocol conclusions data show reliable safety cp autoimmune patients appropriate supervision experienced physicians,0.0
1 5disubstituted acylated 2amino4 5dihydroimidazoles new class retinoic acid receptorrelated orphan receptor ror inhibitors growing body evidence suggests pathogenic role proinflammatory t helper 17 cells th17 several autoimmune diseases including multiple sclerosis rheumatoid arthritis inflammatory bowel disease type diabetes psoriasisdiseases curative treatment currently available nuclear retinoic acid receptorrelated orphan receptors alpha gamma ror particular truncated isoform rort specifically expressed thymus play critical,0.0
protein tyrosine phosphatase receptor type z central nervous system disease gliomas among common tumors central nervous system include highly malignant subtypes glioblastoma associated poor prognosis effective treatments therefore urgently needed despite recent advances neuroimaging technologies differentiating gliomas brain diseases multiple sclerosis remains challenging patients often requires invasive brain biopsy protein tyrosine phosphatase receptor type z ptprz,0.0
neuroprotective potential dendritic cells sirtuins multiple sclerosis myeloid cells including parenchymal microglia perivascular meningeal macrophages dendritic cells dcs present central nervous system cns establish intricate relationship cells playing crucial role health neurological diseases context dcs critical orchestrating immune response linking innate adaptive immune systems steadystate conditions dcs patrol cns sampling local environment,1.0
importance cxcl1 physiology noncancerous diseases bone bone marrow muscle nervous system review describes role cxcl1 chemokine crucial inflammation chemoattractant neutrophils physiology selected major noncancer diseases due vast amount available information focus role cxcl1 plays physiology bones bone marrow muscle nervous system reason describe effects hematopoietic stem cells myoblasts oligodendrocyte progenitors osteoclast precursors also present involvement,0.0
expanding role infectious disease expert context ms centre conclusion increasing awareness potential infectious complications ms exposure dmts interaction ms neurologist infectious disease specialist fundamental minimise infectious risk related disease dmts progressive shift complication management broader prevention workup time ms diagnosis including vaccination prophylactic treatments,0.0
update multiple sclerosis molecular biomarkers monitor treatment effects multiple sclerosis ms inflammatory neurodegenerative disease central nervous system characterized broad inter intraindividual heterogeneity relapse rate disability progression lesion load assessed mri used detect disease activity response treatment although possible standardize characteristics larger patient groups far difficult achieve individual patients easily detectable molecular,0.0
functions potassium channels blocked low micromolar 4aminopyridine crayfish nervous system 4aminopyridine 4ap potassium channel blocker used treat patients multiple sclerosis lamberteaton disease concentration drug blood patients estimated low submicromolar range animal studies shown 4ap low concentration selectively blocks subset channels kv1 kv3 families crayfish opener neuromuscular junction ventral superficial flexor vsf preparations used examine functions,0.0
programmed cell death protein 1positive cd8sup+ sup t cells multiple sclerosis exhausted fighters peacekeepers abstract,0.0
patterns cerebrospinal fluid alzheimers dementia biomarkers people living hiv crosssectional study associated factors according viral control neurological confounders neurocognition people living hiv plwh age excess burden comorbidities may increase incidence agerelated complications controversy surrounding hypothesis hiv can accelerate neurodegeneration alzheimers dementia ad performed retrospective study analyze distribution cerebrospinal fluid csf ad biomarkers beta amyloid 142 fragment tau phosphorylated tau adult plwh cart undetectable viremia n 136 detectable,0.0
prognostic markers ocrelizumab effectiveness multiple sclerosis real world observational multicenter study pivotal trials showed effectiveness monoclonal antibody ocrelizumab relapsing progressive multiple sclerosis ms however data everyday practice ms patients markers treatment effectiveness scarce aimed collect realworld data ocrelizumabtreated ms patients relapsingremitting rr progressive ms patients pms including active secondary progressive ms aspms primary progressive ms ppms patients explore potential prognostic,0.0
b cells specific cpg induces high il10 il6 expression vitro neurobehets disease remittingrelapsingmultiple sclerosis rrms neurobehet disease nbd two chronic neuroinflammatory disorders leading neurological damage herein investigated patients il10producing cells early stages disorders cellular molecular investigations carried treatment naive patients suffering rrms nbd recruited first episode clinical relapse findings demonstrate csfb cells nbd patients,0.0
regulatory aspects biological medicines bosnia herzegovina use biological medicines also called biologics contributed progress treatment many chronic diseases cancer rheumatoid arthritis crohns disease multiple sclerosis psoriasis however biologicals expensive healthcare systems several countries availability global issue affected many patients suffer various diseases biosimilar medicine also called biosimilar medicine similar,0.0
fatigue stigma mood patients multiple sclerosis effectiveness guided imagery conclusions results indicated guided imagery costeffective method can decrease fatigue stigma enhance mood patients ms therefore nursing staff can use method improve ms patients mood decrease fatigue stigma,0.0
matrine derivate masm inhibits astrocyte reactivity alleviates experimental autoimmune encephalomyelitis mice astrocytes ast play important role pathogenesis neurological disorders activation involved progression multiple sclerosis ms 6as 10s 11ar 11br 11cs 10methylaminododecahydro3a 7adiazabenzo de anthracene8thione masm novel derivative matrine exhibits vast pharmacological activities antitumor antifibrosis immune regulation study demonstrate masm promising agent treatment experimental,0.0
possible involvement sema3a sema4a pathogenesis multiple sclerosis conclusion show sema3a regulatory molecule ms whereas sema4a stimulatory one targeting sema3a sema4a become potential therapeutic approach ms,0.0
covid19 vaccination hesitancy among people chronic neurological disorders position paper background health risks associated sarscov2 infection undisputed moreover capability vaccination prevent symptomatic severe fatal covid19 recognized also early evidence vaccination can reduce chance long covid19 nonetheless willingness get vaccinated receive booster shots remains subpar among people neurologic disorders vaccine scepticism jeopardizes collective efforts end covid19 pandemic puts,0.0
isometric tests evaluate upper lower extremity functioning people multiple sclerosis reliability validity abstractbackground upper lower extremity motor symptoms common people multiple sclerosis pwms need develop objective reliable valid outcome measures aim study evaluate reliability external validity standard novel isometric tests assessment neuromuscular functioning upper grip force gf lower knee extensors ke extremities pwmsmethods twentynine relapsingremitting pwms expanded disability status scale edss 6 completed isometric functional tests upper grip force lower knee extension extremity two separate visits isometric testing included maximum force maxf maximum rate force development maxrfd recently developed novel brief force pulse protocol bfp dependent variables bfp included rate force development relaxation scaling factors rfdsf rfrsf quantifies individuals ability scale rates force development relaxation magnitude force pulse produced pwms also completed functional tests upper 9hole peg 9hpt finger tapping ftt lower extremity 25ft walk test t25wt timed go tug 5time sittostand 5sts multiple sclerosis spasticity scale msss88 results isometric outcome measures high reliability iccs087 cvs12 gf rfdsf rfrsf significant associations 9hpt ftt rs 049055 p005 ke maxf maxrfd rfdsf moderately correlated functional tests strongest correlations observed rfrsf t25fw r071 tug r060 5sts r047 msss88 r060 edss r071 multiple linear regression analysis indicated rfdsf predictor 9hpt rfrsf predictor walking speed among studied variablesconclusions bfp protocol provides highly reliable relevant outcome measures evaluate upper lower extremity functioning pwms specifically ability relax muscle forces quickly quick force production highly contributes walking speed pwms,0.0
feedback neurology residents neuroimmunology fellows practical training multiple sclerosis abstractobjective obtain feedback neurology residents neuroimmunology fellows practical training multiple sclerosis ms methods survey developed administered electronically neurology residents neuroimmunology fellows received training eight large ms outpatient clinics brazil 2018 2021 evaluated beliefs 1 optimal number ms patients evaluated 4hour outpatient clinic session 2 quality dedicated ms medical records 3 training neurological exam ms patients 4 teaching discussion attending neuroimmunologist 5 prescription ms diseasemodifying drugs dmds results response rate 57 43 76 found 4 5 ms patients optimal 4hour outpatient clinic session optimal ms medical records considered structured presented timeline disease activity history dmds 18 43 42 respondents felt insecure performing clinical scales used ms patients discussion attending neurologist specialized neuroimmunology considered adequate half respondents suggesting need improvement teaching strategies almost quarter respondents 11 43 26 felt prescription dmds complex challenging respondents suggested readymade templates helpfulconclusion number patients medical records use ms clinical scales discussion attending neurologist specialized ms care prescription dmds present room improvement ms training neurology residents neuroimmunology fellows,0.0
effects safety exergaming persons multiple sclerosis corticosteroid treatment pilot study abstractbackgroundthere information effects usability rehabilitation corticosteroid treatmentthis randomized clinical trial conducted evaluate compare effects safety exergaming conventional rehabilitation cr persons multiple sclerosis ms pwms corticosteroid treatmentmethodsthe participants randomly divided two groups exergaming n15 cr n15 rehabilitation applied physiotherapist expertise ms measurements done baseline t1 immediately discharge t2 1 month discharge t3 outcome measures includedupper extremity functions walking balance cognitive functions quality life depression fatigueresultsthe nine hole peg test california verbal learning test symbol digit modalities test ms walking scale12 six spot step test showed significant difference t1 t2 t1 t3 exergaming cr groups p 005 timed 25 foot walk multiple sclerosis international quality life questionnaire significantly different t1 t3 exergaming cr groups p 005 brief visuospatial memory testrevised significantly different t1 t3 t2 t3 exergaming cr groups p 005 mfis showed significant difference t1 t2 t1 t3 exergaming group p 005 conclusionsthis study suggests thatexergaming cr effective safe methods improving upper extremity cognitive functions fatigue quality life balance walking ability pwms hospitalization period,0.0
faster bcell repletion anticd20 infusion black patients compared white patients neurologic diseases summarythis retrospective singlecenter study aimed characterize compare kinetics bcell reemergence following anticd20 infusion anticd20i african american aa white patients ms nmosd logistic regression model included race time since anticd20i body mass index diagnosis aa race p001 time since anticd20i p00003 significant predictors bcell repletion however bcell subset composition similar aa white patients detectable cd19+ bcell counts findings highlight importance including diverse study population future studies anticd20 therapies,0.0
german guideline diagnosis treatment multiple sclerosis survey focusing neurologists daily practise abstractwe performed webbased survey among germanspeaking neurologists evaluate acceptance 2021 german guideline diagnosis treatment multiple sclerosis based 327 replies total current survey largely reproduced findings earlier smaller survey prefinal consultation version guideline confirmed high acceptance rates half participants practising neurologists neurologists ms centers 500 patients per year n26 critical guideline reiterated criticisms previous feedback particular felt safety aspects overemphasized guideline thereby superseding early aggressive therapy,0.0
prevalence internuclear ophthalmoparesis populationbased cohort individuals multiple sclerosis abstractbackgroundinternuclear ophthalmoparesis ino occurs 1552 individuals multiple sclerosis ms reliably detected infrared oculography methods diagnosing ino infrared oculography association ino ms characteristics need confirmation aimed describe ino prevalence clinical characteristics individuals ms ino populationbased cohort individuals ms born year 1966 project y methodspreviously described thresholds versional dysconjugacy index vdi assessed standardized infrared oculography used detect ino participants project y clinical characteristics visual functioning complaints compared individuals ms ino individuals ms without inoresultstwohundredtwenty individuals ms 110 healthy controls included vdi values exceeding threshold ino presented 53 24 individuals ms 19 controls 13 ino associated male sex greater disability worse cognition worse arm function individuals ms association disease duration visual functioning complaintsconclusionsino prevalent among individuals ms aged fiftythree related clinical characteristics ms ino frequently detected healthy controls previous studies implying oculography based diagnosis ino requires refinement,0.0
characterization immune profile aging multiple sclerosis clinic population backgroundthere limited data regarding adaptive immunity older persons multiple sclerosis ms objectivethe aim present study quantify adaptive immune cells younger age less 50 older age greater 50 ms context clinical parameters edss 25foot walk sdmt subjects either untreated ms medications 6 months taking injectables interferons glatiramer acetate approved ms treatmentsresultsa total 72 subjects enrolled 30 younger 42 older older ms patients untreated taking injectables lower cd8 cell counts older ms patients demonstrated increased levels cd4+cd25hi cells inflammatory serum cytokines tnf il8 suggestion ms treatments modulated il10 cognition assessed sdmt associated disease duration il10conclusioncomponents adaptive immunity influenced aging ms may also impact aspects cognition measured sdmt,0.0
incomplete reporting patientreported outcomes multiple sclerosis metaepidemiological study randomized controlled trials background multiple sclerosis significantly affects quality life often measured patientreported outcomes incorporation patientreported outcomes within clinical trials supplements efficacy outcomes order provide patients perspective clinicians objective evaluate current literature completeness reporting pros randomized controlled trials rcts management msmethods used medline embase cochrane central register controlled trials search rct publications investigating management ms duplicate screening via rayyan rcts fitting inclusion criteria abstracted employing consolidated standards reporting trials patientreported outcome consortpro adaptation cochrane collaboration risk bias rob 20 tool mean percent completion adaptation consortpro calculated address completeness reporting addition bivariate regression models used evaluate relationships trial characteristics completeness reportingresults search returned 3 966 results 92 rcts included data abstraction analysis found overall completion 4868 sd1903 sixtyfive 92 7065 rcts evaluated high rob significant associations completeness reporting following mention consort within published rcts t255 p013 length pro followup t29 p005 t214 p035 sample size t312 p002 significant associations foundconclusion study found incomplete adherence consortpro adaptation among rcts pertaining ms underreported items failure report hypothesis define approach missing data threaten validity evidence acquired rcts furthermore pros provide opportunity supplement trial outcomes patients perspective thus trialists future rcts may improve pro reporting increased adherence consortpro adaptation,0.0
incomplete reporting patientreported outcomes multiple sclerosis metaepidemiological study randomized controlled trials abstractbackgroundmultiple sclerosis significantly affects quality life often measured patientreported outcomes incorporation patientreported outcomes within clinical trials supplements efficacy outcomes order provide patients perspective clinicians objective evaluate current literature completeness reporting pros randomized controlled trials rcts management msmethodswe used medline embase cochrane central register controlled trials search rct publications investigating management ms duplicate screening via rayyan rcts fitting inclusion criteria abstracted employing consolidated standards reporting trials patientreported outcome consortpro adaptation cochrane collaboration risk bias rob 20 tool mean percent completion adaptation consortpro calculated address completeness reporting addition bivariate regression models used evaluate relationships trial characteristics completeness reportingresultsour search returned 3 966 results 92 rcts included data abstraction analysis found overall completion 4868 sd1903 sixtyfive 92 7065 rcts evaluated high rob significant associations completeness reporting following mention consort within published rcts t255 p013 length pro followup t29 p005 t214 p035 sample size t312 p002 significant associations foundconclusionour study found incomplete adherence consortpro adaptation among rcts pertaining ms underreported items failure report hypothesis define approach missing data threaten validity evidence acquired rcts furthermore pros provide opportunity supplement trial outcomes patients perspective thus trialists future rcts may improve pro reporting increased adherence consortpro adaptation,0.0
personality traits patients multiple sclerosis correlation anxiety depression levels crosssectional casecontrol study conclusions conclusion anxiety depression levels much higher among ms patients compared controls severity conditions correlate score disability index therefore complete comprehension conditions neurologist vital improving patients qol increasing compliance adherence pharmacological therapy,0.0
microtubule dynamics following central peripheral nervous system axotomy disturbance neuronal network leads instability microtubule mt railroad axons causing hindrance intraaxonal transport making difficult reestablish broken network peripheral nervous system pns neurons can stabilize mts leading formation regenerationpromoting structures called growth cones however central nervous system cns neurons lack intrinsic reparative capability instead form growthincompetent structures,0.0
safety efficacy fingolimod realworld data longterm noninterventional study treatment rrms patients spanning 5 years hungary conclusion nationwide hungarian cohort patients fingolimod treatment free relapses disability progression addition fingolimod proven welltolerated dmt sustained manageable safety profile high efficacy positive benefit risk ratio 5 years reallife setting,0.0
photobiomodulation modulates interleukin10 interferon gamma production mononuclear cells healthy donors persons multiple sclerosis background photobiomodulation pbm therapy previously shown reduce clinical severity disease modulated pro antiinflammatory cytokines animal model multiple sclerosis ms objective previous observations extended determine effect pbm therapy peripheral blood mononuclear cells cd4 + t cells isolated persons ms pwms healthy donors methods using vitro cell culture system isolated cells activated treated,0.0
realworld evidence cladribine tablets multiple sclerosis insights efficacy safety cladribine clad purine nucleoside analog approved tablet form treat highly active multiple sclerosis ms clad tablets first oral therapy infrequent dosing schedule administered two annual treatment courses divided two treatment cycles comprising 45 days treatment efficacy safety clad tablets verified randomized controlled clinical trials clinical observational studies performed representative populations,0.0
italian translation validation fatigue symptoms impacts questionnaire relapsing multiple sclerosis fsiqrms conclusion italian version fsiqrms excellent psychometric properties can used research clinical setting evaluate physical cognitive social fatigue rms spms,0.0
personalized disease monitoring pediatric onset multiple sclerosis using saliva free light chain test conclusions results show potential noninvasive saliva flc test new tool monitoring disease activity poms,0.0
effects emgcontrolled video games upper limb functionality patients multiple sclerosis feasibility study development description multiple sclerosis ms common inflammatory neurological disease young adults high prevalence worldwide 28 million people aid ms treatment using vr tools cognitive motor rehabilitation disease growing progressively last years however role vr rehabilitative tool ms treatment still debate paper explores effects vr training using emg activation upper limb functionality experimental,0.0
aim2 inflammasome activated astrocytes late phase eae inflammasomes class innate immune signaling platforms activate response array cellular damage pathogens inflammasomes promote inflammation many circumstances enhance immunity pathogens inflammatory responses effector cytokines il1 il18 multiple sclerosis animal model experimental autoimmune encephalomyelitis eae autoimmune conditions influenced inflammasomes despite work investigating inflammasomes,0.0
role diet gut microbiota regulating gastrointestinal inflammatory disease diet important lifestyle factor known contribute development human disease well established poor diet plays active role exacerbating metabolic diseases obesity diabetes hypertension understanding immune system drives chronic inflammation disease pathogenesis evolved recent years however contribution dietary factors inflammatory conditions inflammatory bowel disease multiple sclerosis,0.0
discovery phospholipase d inhibitors improved druglike properties central nervous system penetrance phospholipase d pld phospholipase enzyme responsible hydrolyzing phosphatidylcholine lipid signaling molecule phosphatidic acid choline therapeutic perspective pld implicated human cancer progression well target neurodegenerative diseases including alzheimers moreover knockdown pld rescues als phenotype multiple drosophila models als amyotrophic lateral sclerosis displays modest motor benefits sod1 als mouse,0.0
brainderived neurotrophic factor neurofilament light chain cerebrospinal fluid inversely correlated cognition multiple sclerosis time diagnosis abstractbackgroundcognitive performance may impaired ms even earliest stages disease tested whether brainderived neurotrophic factor neurofilament light chain levels serum cerebrospinal fluid csf samples snfl cnfl sbdnf cbdnf collected time diagnosis associated cognitive performancemethodswe measured snfl cnfl sbdnf cbdnf using singlemolecule array simoa 47 newly diagnosed patients 32 relapsingremitting ms 6 primary progressive ms 9 clinically isolated syndrome partial correlations average zscore neuropsychological tests snfl sbdnf cnfl cbdnf computed adjusting covariates multivariate analysis covariance determined effect cognitive status biomarker levels composite measure nfl bdnf submitted similar exploratory analysisresultscognitive performance correlated inversely cnfl r0451 q0032 cbdnf r0406 q0034 impairment least two different tests linked higher cnfl p0011 cbdnf p0035 levels compared impairment one test cnfl also compared impairment p001 composite csf biomarker measure accounting cnfl cbdnf correlated strongly tests information processing p0048 verbal learning memory consolidation p002 compared single csf biomarkersconclusionscsf bdnf nfl levels measured time diagnosis inversely associated cognitive performance ms findings suggest csf biomarkers linked different pathophysiological processes reflect neuropsychological impairment earliest stages disease combining different csf measures might facilitate developing better biomarker cognition ms,0.0
validation two new scales assessment fatigue multiple sclerosis f2ms facitf abstractbackground fatigue one common symptoms neurology especially ms patients prevalence 65 described disabling symptom 40 ms patients study aimed validate functional assessment chronic illness therapy fatigue version facitf f2ms scale new tool distinguish fatigue fatigabilitymethods one hundred fifteen patients relapsingremitting ms enrolled patients completed comprehensive neuropsychological battery previously validated ms fatigue evaluated using fatigue severity scale fss modified version fatigue impact scale mfis functional assessment chronic illness therapy measure system fatigue version fcitf new tool assessment fatigue fatigability f2ms scale internal consistency estimated cronbachs alpha intergroup comparisons students ttest pearsons chisquared test used pearsons correlation test calculated quantitative variables cohens d calculated evaluate effect size binary logistic regression performed considering presence fatigue criterion variable facitf f2ms scores added predictor variables roc curves also estimated conducted confirmatory factor analysis f2ms scale considering two latent factorsresults facitf f2ms showed high internal consistency scales highly correlated mfis fss showed low correlation symbol digit modalities test significant differences fatigued nonfatigued patients facitf f2ms scores large effect sizes scales showed auc 090 achieved correct classification 87 confirmatory factor analysis showed moderate evidence two dimensions f2ms scaleconclusions facitf f2ms scales showed appropriated psychometric properties used fatigue measures clinical research settings allowing correct distinction patients without fatigue contributing understanding complexities fatigue ms,0.0
metabolic potential paediatriconset multiple sclerosis gut microbiome abstractbackgroundthe aim study examine gut microbiomes metabolic potential paediatriconset ms patients symptom onset 18 years methodswe included 17 ms participants 20 controls similar sex age race stool consistency canadian paediatric demyelinating disease network study stoolderived gut metagenome gene abundances used estimate relative abundances turnover scores individual microbial metabolites composition diversity carbohydrateactive enzymes cazymes ms participants controls compared using wilcoxon ranksum test diseasemodifying drug dmd exposed nave ms participantsresultsthe median age s ms symptom onset161 years interquartile range iqr 17 stool sample procurement169 158 years iqr20 14 ms participants controls ms control participants girls 8082 five 29 ms participants never exposed dmd prestool sample 12 71 7 betainterferon 5 glatiramer acetate relative abundance metabolites differ ms participants controls turnover scores ms participants greater potential metabolize lipopolysaccharides controls score difference16e04 p0034 lower potential metabolize peptidoglycan molecules starch score differences22e02 p0040 although cazymes diversity differ p0050 starchdegrading subfamilies underrepresented ms participants versus controls relative abundance differences 034 p0040 dmd exposed verses dmd nave ms participants relative abundance differences020 p0049 conclusionpaediatriconset ms participants altered gut microbiomerelated metabolic potential compared controls including higher breakdown lipopolysaccharide molecules lower resistant starch metabolism,1.0
brainderived neurotrophic factor neurofilament light chain cerebrospinal fluid inversely correlated cognition multiple sclerosis time diagnosis abstractbackground cognitive performance may impaired ms even earliest stages disease tested whether brainderived neurotrophic factor neurofilament light chain levels serum cerebrospinal fluid csf samples snfl cnfl sbdnf cbdnf collected time diagnosis associated cognitive performancemethods measured snfl cnfl sbdnf cbdnf using singlemolecule array simoa 47 newly diagnosed patients 32 relapsingremitting ms 6 primary progressive ms 9 clinically isolated syndrome partial correlations average zscore neuropsychological tests snfl sbdnf cnfl cbdnf computed adjusting covariates multivariate analysis covariance determined effect cognitive status biomarker levels composite measure nfl bdnf submitted similar exploratory analysisresults cognitive performance correlated inversely cnfl r0451 q0032 cbdnf r0406 q0034 impairment least two different tests linked higher cnfl p0011 cbdnf p0035 levels compared impairment one test cnfl also compared impairment p001 composite csf biomarker measure accounting cnfl cbdnf correlated strongly tests information processing p0048 verbal learning memory consolidation p002 compared single csf biomarkersconclusions csf bdnf nfl levels measured time diagnosis inversely associated cognitive performance ms findings suggest csf biomarkers linked different pathophysiological processes reflect neuropsychological impairment earliest stages disease combining different csf measures might facilitate developing better biomarker cognition ms,0.0
kappa free light chains cerebrospinal fluid inflammatory noninflammatory neurological diseases conclusions determination biomarkers kflc oligoclonal bands recommended routine diagnosis differentiation noninflammatory inflammatory neurological diseases due high sensitivity physiological considerations assessment kflc reibers diagram preferred evaluation methods,0.0
first report tumor treating fields ttfields therapy glioblastoma comorbidity multiple sclerosis tumor treating fields ttfields therapy fda approved ce mark treatment newly diagnosed recurrent glioblastoma knowledge date ttfields therapy remains unstudied glioblastoma patients multiple sclerosis ms comorbidity present patient diagnosed ms age 34 treatment included several corticoid pulse treatments therapies interferon beta1a sphingosine1phosphate receptor modulator fingolimod,0.0
development evaluation website patients experiences multiple sclerosis mixed methods study conclusions findings suggest pexms website might potential useful source audiovisual information persons ms given lack websites available patients experiential information health care professionals may encouraged routinely inform patients website regular appointments,0.0
extracorporeal photopheresis systemic sclerosis metaanalysis randomized clinical trials conclusions evidence base extracorporeal photopheresis skin scores patients systemic sclerosis high enough support superior effect compared treatment sham photopheresis dpenicillamine article protected copyright rights reserved,0.0
quality life people solid cancer less worse diseases better prognosis except presence depression conclusion findings confirm strong impact sc showed hqol sc higher chronic diseases better quoad vitam outcome since depression strong determinant prevention early detection therapy main objectives must reached cancer patients,0.0
qualitative study identifies life shifts stress coping strategies people multiple sclerosis multiple sclerosis ms autoimmune disease bodys immune system attacks central nervous system demyelination nerve fibers can lead physical emotional cognitive impairments wanted learn challenges living illness people deal stress 128 individuals ms austria us participated qualitative interviews interviewed participants coded answers using inductive grounded theory asked,1.0
effects exergaming cognition lower limb functional coordination stepping time people multiple sclerosis randomized controlled trial conclusions shortterm exergames led improvements complex attention executive function lowerlimb functional coordination comparing matched conventional exercises midterm exergaming effective improving stepping time lowerlimb functional coordination however two approaches show superiority improving simple attention rtimplications rehabilitationwhen designed properly exergames great potential,0.0
systemic infection nonemalbicans candida em species affects development murine model multiple sclerosis candidiasis may affect central nervous system cns although candida albicans predominant nonalbicans candida species can also associated cns infections studies suggested candida infections increase odds multiple sclerosis ms development context investigated whether systemic infection nonalbicans candida species affect clinically immunologically severity experimental autoimmune encephalomyelitis eae,0.0
nimodipine exerts beneficial effects rat oligodendrocyte cell line oln93 multiple sclerosis ms chronic autoimmune disease central nervous system cns therapy currently limited drugs interfere immune system treatment options primarily mediate neuroprotection prevent neurodegeneration available studied effects nimodipine rat cell line oln93 resembles young mature oligodendrocytes nimodipine dihydropyridine blocks voltagegated ltype calcium channel family members,0.0
human myelin proteome submetalloproteome interaction map relevance myelinrelated neurological diseases myelin humans composed 80 lipids 20 protein initially myelin protein composition considered low various recent proteome analyses identified additional myelin proteins although myelin proteome qualitatively quantitatively identified complementary proteomic approaches corresponding proteinprotein interaction ppi network myelin yet available present work ppi network constructed based available,1.0
multiregression approach improve optical coherence tomography diagnostic accuracy multiple sclerosis patients without previous optic neuritis conclusion capability oct ms differentiation made robust accounting oct scans individual anatomical differences incorporating information optic disc macular regions representing markers axonal damage neuronal injury respectively,0.0
healthcare resource utilization costs extended interval dosing natalizumab multiple sclerosis aims natalizumab approved infusion every 4 weeks standardinterval dosing sid relapsingremitting multiple sclerosis ms extendedinterval dosing eid reduces risk progressive multifocal leukoencephalopathy pml compared sid impact healthcare resources costs remains unknown methods populationbased study included 208 natalizumabtreated ms patients classified eid 15 infusions previous 18 months n 51 age 337,0.0
impact antiinfective screening monitoring protocol together infectious disease consultation preventing infective adverse events patients treated anticd20#x2f cd52 agents multiple sclerosis abstractbackground monoclonal antibodies milestone treatment multiple sclerosis ms infective complications observed patients agents targeting lymphoid cells surface antigens namely anticd52 alemtuzumab anticd20 agents ocrelizumab rituximab despite increasing emerging data standardized consensus regarding pretreatment testing vaccinations patient education ms therapy optimal infectioncontrol strategiesmethods led retrospective prospective reallife study evaluate effectiveness program screening prophylaxis infective adverse events patients multiple sclerosis related disorders treated drugs directed cd20 52 antigens patients referring ms clinical care research center university naples federico ii started alemtuzumab ocrelizumab rituximab offlabel use 1 november 2015 30 june 2019 recruited 1st february 2018 patients underwent microbiological screening evaluated infectious disease specialist ids monoclonal antibodies infusion rule active infections evaluated incidence infective complications predictors retrospectively prospectively introduction abovementioned antiinfective programresultswe enrolled 275 patients 104 retrospectively preintervention group pre 171 prospectively postintervention group post pre group patients treated alemtuzumab 58 vs 32 p0001 frequently dmt nave 48 vs 36 p0044 received fingolimod past 48 vs 28 p0044 followup period longer post group 750 vs 191 days p0001 post group patients older median age 47 vs 42 years p0030 mostly received ocr 54 vs 14 p0001 lymphopenia baseline significantly commonly observed pre arm 47 vs 8 p0001 total 39 patients 38 pre arm 42 patients 25 post group experienced one infections p0022 severe infections significantly common pre patients 23 vs 14 p0022 antiinfective program associated lower iae incidence univariate multivariate analysis ahr infective events pre group 3652 ci 9039419 p 0001 moreover dmt nave patients significantly experienced fewer infective complications ahr 0470 ci 102255 p0040 conclusionsa risk mitigation program including infectious disease consultation standardized screening prophylactic protocols effective reducing infective adverse events patients receiving anti cd20 cd52 agents ms,0.0
impact antiinfective screening monitoring protocol together infectious disease consultation preventing infective adverse events patients treated anticd20#x2f cd52 agents multiple sclerosis abstractbackgroundmonoclonal antibodies milestone treatment multiple sclerosis ms infective complications observed patients agents targeting lymphoid cells surface antigens namely anticd52 alemtuzumab anticd20 agents ocrelizumab rituximab despite increasing emerging data standardized consensus regarding pretreatment testing vaccinations patient education ms therapy optimal infectioncontrol strategiesmethodswe led retrospective prospective reallife study evaluate effectiveness program screening prophylaxis infective adverse events patients multiple sclerosis related disorders treated drugs directed cd20 52 antigens patients referring ms clinical care research center university naples federico ii started alemtuzumab ocrelizumab rituximab offlabel use 1 november 2015 30 june 2019 recruited 1st february 2018 patients underwent microbiological screening evaluated infectious disease specialist ids monoclonal antibodies infusion rule active infections evaluated incidence infective complications predictors retrospectively prospectively introduction abovementioned antiinfective programresultswe enrolled 275 patients 104 retrospectively preintervention group pre 171 prospectively postintervention group post pre group patients treated alemtuzumab 58 vs 32 p0001 frequently dmt nave 48 vs 36 p0044 received fingolimod past 48 vs 28 p0044 followup period longer post group 750 vs 191 days p0001 post group patients older median age 47 vs 42 years p0030 mostly received ocr 54 vs 14 p0001 lymphopenia baseline significantly commonly observed pre arm 47 vs 8 p0001 total 39 patients 38 pre arm 42 patients 25 post group experienced one infections p0022 severe infections significantly common pre patients 23 vs 14 p0022 antiinfective program associated lower iae incidence univariate multivariate analysis ahr infective events pre group 3652 ci 9039419 p0001 moreover dmt nave patients significantly experienced fewer infective complications ahr 0470 ci 102255 p0040 conclusionsa risk mitigation program including infectious disease consultation standardized screening prophylactic protocols effective reducing infective adverse events patients receiving anti cd20 cd52 agents ms,0.0
preventing disease progression multiple sclerosisinsights large realworld cohorts multiple sclerosis chronic neuroinflammatory disease highly heterogeneous disease course preventing lasting disability requires early identification persons risk novel approaches towards patient stratification personalized treatment decisions comment discuss importance large datasets realworld cohorts order address unmet need,0.0
white matter tract conductivity resistant wide variations paranodal structure myelin thickness accompanying loss tyro3 experimental simulated analysis myelination within central nervous system cns crucial conduction action potentials neurons variation compact myelin morphology structure paranode hypothesised significant impact speed action potentials however limited experimental data investigating impact changes myelin structure upon conductivity central nervous system used genetic model myelin thickness reduced investigate,1.0
epsteinbarr virus multiple sclerosis new light old idea bjornevikkcortesemhealybckuhlejminamjlengy others 2022 longitudinal analysis reveals high prevalence epsteinbarr virus associated multiple sclerosis science375 6578 296301 lanztvbrewerrchoppmoonjsjudekmfernandezd others clonally expanded b cells multiple sclerosis bind ebv ebna1 glialcam nature2022 6033217 abstract,0.0
overview role tumor necrosis factoralpha epileptogenesis terapeutic implications complex association neuroinflammation seizures widely investigated recent years mediators inflammatory response cytokines like tumor necrosis factor tnfa potential therapeutic targets epileptic disorders tnfa pleiotropic cytokine controversial role epileptogenesis seemingly capable favor genesis seizures elicit neuromodulatory responses antitnf agents group monoclonal antibodies engineered,0.0
iguratimod inhibits skin fibrosis regulating tgf1 smad signaling pathway systemic sclerosis conclusion preliminary data indicated t614 inhibited dermal fibroblasts activation skin fibrosis least partly regulating tgf1 smad pathway experimental ssc models may promising therapeutic agent ssc,0.0
association neurodevelopmental abnormalities congenital heart renal defects tuberous sclerosis complex patient cohort conclusions study marks first empirical investigation comorbidity congenital heart defects chd ndds kds tsc1 tsc2 patients remains unique first step towards characterisation dynamic role genetics heart function brain function kidney function early development context tsc,0.0
alzheimers diseaserelated psychosis overview clinical manifestations pathogenesis current treatment behavioral psychotic manifestations including aggression delusions hallucinations frequent comorbidities patients debilitating nervous illnesses alzheimers disease ad amyotrophic lateral sclerosis multiple sclerosis parkinsons disease adrelated psychosis may linked poor disease prognosis highlighting early detection management mandatory manifestations variable may heterogeneous imposing real diagnostic,0.0
patientbased benefitrisk assessment medicines development refinement validation content search strategy retrieve relevant studies introduction poor indexing inconsistent use terms keywords may prevent efficient retrieval studies patientbased benefitrisk assessment bra medicines aimed develop validate objectively derived content search strategy containing generic search terms can adapted search evidence patientbased bra medicines therapeutic area,0.0
central stress processing tcell responsivity stress hormones disease severity multiple sclerosis epidemiological clinical neuroscientific studies support link psychobiological stress multiple sclerosis neuroimaging suggests blunted central stress processing goes along higher multiple sclerosis severity neuroendocrine studies suggest blunted immune system sensitivity stress hormones linked stronger neuroinflammation now however effort made elucidate whether central stress processing immune system sensitivity stress,0.0
unbiased metabolome screen leads personalized medicine strategy amyotrophic lateral sclerosis amyotrophic lateral sclerosis rapidly progressive neurodegenerative disease affects 1 350 individuals united kingdom cause amyotrophic lateral sclerosis unknown majority cases twosample mendelian randomization enables causal inference exposure serum concentration specific metabolite disease risk obtained genomewide association study summary statistics serum concentrations 566 metabolites population,0.0
somatic variants diverse genes leads spectrum focal cortical malformations postzygotically acquired genetic variants somatic variants arise cortical development emerged important causes focal epilepsies particularly due malformations cortical development pathogenic somatic variants identified many genes within pi3kaktmtorsignaling pathway individuals hemimegalencephaly focal cortical dysplasia type ii recently slc35a2 individuals focal cortical dysplasia type,0.0
minimally detectable change speech intelligibility speakers multiple sclerosis parkinsons disease conclusions agreement previous work als conducted similar conditions ie orthographic transcription sit sentences quiet listening environment mdc 95 speech intelligibility ranged 3 10 speakers ms pd mildly impaired speech estimates step toward development universal language evaluate speech changes variety patient populations,0.0
embodied learning multiple sclerosis using melodic sound visual feedback potential rehabilitation approach given prevalence motor cognitive functions persons multiple sclerosis pwms proposed theoretical framework embodiment provide rehabilitation avenue train functions one functional unit pwms n 31 age gendermatched healthy controls n 30 underwent embodied learning protocol involved learning cognitive sequence performing bodily stepping movement three feedback conditions melody sound,0.0
effect peer education based penders health promotion model quality life stress management selfefficacy patients multiple sclerosis randomized controlled clinical trial conclusion peer education based penders health promotion model improves patients quality life stress management selfefficacy multiple sclerosis nursing managers health system policymakers can use educational approach patients chronic diseases enhance quality life selfefficacy,0.0
outcomes total hip arthroplasty patients without multiple sclerosis retrospective cohort study conclusions although patients ms underwent tha 90day complication risk similar without ms risk requiring revision surgery 2fold higher additional studies needed understand reasons revision surgery developing strategies mitigate risk complications,0.0
research progress role regulatory mechanism pathogenic th17 cells neuroinflammation neuroinflammation complex immune response central nervous system various factors injury infection toxins interfere homeostasis involving variety immune cells lingering central nervous system persistent neuroinflammation common denominator etiology course neurological diseases including neurodevelopmental neurodegenerative psychiatric disorders alzheimers disease parkinsons disease multiple,0.0
longterm cognitive outcomes socioprofessional attainment people multiple sclerosis childhood onset background objectives patients pediatriconset multiple sclerosis ms can especially vulnerable cognitive impairment ci due onset ms critical period cns development maturation objective longitudinal study assess longterm cognitive functioning socioprofessional attainment italian pediatric ms cohort previously assessed baseline 2 5 years,0.0
olfactory dysfunction patients multiple sclerosis systematic review metaanalysis conclusion results systematic review show prevalence olfactory dysfunction ms patients high attention needs drawn aspect ms,0.0
brutons tyrosine kinase inhibitors similar efficacy risks abstract,0.0
alemtuzumab induced hemodynamic change relapsing multiple sclerosis occurs independent corticosteroid premedication retrospective multicentre study abstractbackground alemtuzumab atz highly effective disease modifying treatment relapsing multiple sclerosis ms associated rare risk intracerebral haemorrhage increase blood pressure bp hypothesized causative prior administration highdose methylprednisolone hdmp potential confounderobjective analyse bp change ms patients treated atz prior hdmp treatment compared patients receiving hdmp acute relapsemethods retrospective study 30 patients treated atz hdmp 60 age sex disabilitymatched controls treated hdmp included primary endpoint change systolic bp sbp atz cycle maximum value measured treatment cycle secondary endpoints change diastolic bp dbp heart rate hr results change sbp observed atz hdmp treated patients significantly higher hdmp controls mean maximal change 128 mmhg vs 81 mmhg p0033 increase sbp exceeding 20 baseline observed 5 167 patients atz hdmp compared 3 50 hdmp p0078 day 1st atz infusion mean hr higher atz hdmp group compared hdmp controls 825 vs 732 bpm p0005 although significant group difference timeconclusions atz treatment induced slight significant increase sbp independent hdmp although hemodynamic alterations alone seem unlikely putative mechanism cerebral bleedings strict cardiovascular monitoring recommended reduce rare severe cardiovascular side effects,0.0
chronic cortical inflammation cognitive impairment immune reactivity associated diffuse brain injury ameliorated forced turnover microglia ,1.0
experiences people multiple sclerosis work towards understanding needs job retention vocational rehabilitation intervention conclusion impact environmental factors eg attitudes towards disability employment difficulties equal greater diseaserelated factors environmental changes attitudes coworkers workplace flexibility can enable people ms remain work longer,0.0
guts imbalance imbalances brain review gut microbiota association neurological psychiatric disorders last 10 years growing interest relationship gut microbiota brain neurologicassociated affections multiple preclinical clinical research studies highlight gut microbiotas potential modulate general state health state goes without saying gut microbiota plays significant role neurogenesis mental cognitive development emotions behaviors progression neuropsychiatric illnesses gut,0.0
humoral cellular immune responses sarscov2 mrna vaccination patients multiple sclerosis israeli multicenter experience following 3 vaccine doses conclusion pwms treated dmts developed humoral tcell responses following 2 3 mrna sarscov2 vaccinations fingolimod ocrelizumabtreated patients diminished humoral responses fingolimod compromised cellular responses improvement 3 rd booster vaccination following 5 months since ocrelizumab infusion associated better seropositivity findings may contribute development treatmentstratified vaccination guidelines,0.0
dual biologic therapy ocrelizumab multiple sclerosis vedolizumab crohns disease case report review literature conclusion dbt may safe effective option treatment refractory disease multiple immunemediated diseases newer biologics improved safety profiles gut specificity may provide promising avenues treatment however caution must exercised appropriate selection biologics given inherent immunosuppressive properties side effects efficacy profiles current evidence suggests biologic therapy associated worse,0.0
fuzzy expert system early diagnosis multiple sclerosis conclusion proposed expert system study can analyze symptoms patients predict multiple sclerosis disease therefore can investigate initial status patients rapid costeffective manner moreover system can applied situations places human experts unavailable,0.0
efficacy disease modifying therapies progressive ms immune senescence may explain failure advent disease modifying therapies dmt past two decades cornerstone successful clinical management multiple sclerosis ms despite great strides made reducing relapse frequency occurrence new signal changes neuroimaging patients relapsing remitting ms rrms approved dmt challenging demonstrate effectiveness nonactive secondary progressive ms spms primary progressive ms ppms disease phenotypes,0.0
cardiovascular imaging systemic sclerosis monitoring management systemic sclerosis ssc complex connective tissue disease multiple clinical subclinical cardiac manifestations ssc can affect structural components heart including pericardium myocardium valves conduction system damaging cycle inflammation ischemia fibrosis cardiac involvement second leading sscrelated cause death frequently clinically silent early disease often missed routine screening facilitate,0.0
status epilepticus early development neuronal injury neurodegeneration consequences evidence showing immature brain vulnerable seizureinduced damage accumulating decades clinical data always suggested early life seizures associated negative sequellae clinical observations frequently obscured multiple uncontrolled contributing factors can rarely establish causality determining certainty seizures per se can cause neuronal death can irreversibly disrupt critical developmental processes,0.0
prognostic value serum neurofilament light chain disease activity worsening patients relapsing multiple sclerosis results phase 3 asclepios ii trials conclusion study confirms baseline snfl levels prognostic future onstudy lesion formation whole brain regional atrophy rms patients including recently diagnosed treatmentnaive patients,0.0
effective connectivity within papez circuit multiple sclerosis patients comparative study using restingstate fmri conclusion present study reveals significant difference effective connectivity papez nodes ms patients control group can exploited diagnosis predict evaluate treatment response patients,0.0
pseudobulbar affect neurodegenerative diseases systematic review metaanalysis conclusion review showed pba common patients neurodegenerative diseases including pd ad ms especially als due lack proper recognition medication treatment effective sufficient therefore can dramatically lower quality life pba patients decrease social interactions,0.0
association circulating micrornas hsamir92a1 hsamir454 multiple sclerosis phenotypes activity status efficient diagnosis multiple sclerosis ms disease along early prediction progression will ultimately lead better management control complications improvement therapeutic outcomes patients wellbeing blood based biomarkers like circulating micrornas represent non invasive fast easily measured markers promising potential work intended assess relative expression circulating hsamir454 hsamir92a1 diagnostic,0.0
validity reliability korean version modified fatigue impact scale mfis korean patients multiple sclerosis abstractbackground determine validity reliability korean version modified fatigue impact scale mfisk questionnaire patients multiple sclerosis ms methods prospectively enrolled 52 patients ms 102 healthy controls subjects asked complete korean version fatigue severity scale fss mfisk evaluate sleep quality depression pain quality life patients completed pittsburgh sleep quality index psqi beck depression scale ii bdi brief pain inventory bpi short form 36 health survey sf36 results demonstrated mfisk appropriate construct validity distinctive 3 factors cognitive physical psychosocial criterion validity also confirmed total score factor scores patients ms significantly higher healthy controls convergent validity mfisk verified correlations fatigue severity scale fss concurrent measures sleep disturbances depression pain limitations activities due health problems furthermore internal consistency temporal stability score consistency mfisk turned acceptablediscussion results indicate korean version mfis valid reliable scale assess fatigue korean ms population,0.0
validity reliability korean version modified fatigue impact scale mfis korean patients multiple sclerosis abstractbackgroundto determine validity reliability korean version modified fatigue impact scale mfisk questionnaire patients multiple sclerosis ms methodswe prospectively enrolled 52 patients ms 102 healthy controls subjects asked complete korean version fatigue severity scale fss mfisk evaluate sleep quality depression pain quality life patients completed pittsburgh sleep quality index psqi beck depression scale ii bdi brief pain inventory bpi short form 36 health survey sf36 resultsit demonstrated mfisk appropriate construct validity distinctive 3 factors cognitive physical psychosocial criterion validity also confirmed total score factor scores patients ms significantly higher healthy controls convergent validity mfisk verified correlations fatigue severity scale fss concurrent measures sleep disturbances depression pain limitations activities due health problems furthermore internal consistency temporal stability score consistency mfisk turned acceptablediscussionour results indicate korean version mfis valid reliable scale assess fatigue korean ms population,0.0
ubiquitinbinding domain abin1 critical regulating cell death inflammation development abin1 polyubiquitinbinding protein known regulate nfb activation cell death signaling mutations abin1 can cause severe immune diseases human psoriasis systemic lupus erythematosus systemic sclerosis generated mice disrupted ubiquitinbinding domain abin1 abin1 ubd ubd died later embryogenesis owing tnfr1mediated cell death similar abin1 mice abin1 ubd ubd cells rendered sensitive tnfinduced,0.0
cytokines interleukin6 interferon induce distinct microglia phenotypes conclusions findings demonstrate microglia responses il6 ifn highly stimulusspecific wideranging give rise divergent phenotypes modulate microglia responses neuroinflammatory neurodegenerative diseases,0.0
kidney transplantation patient tuberous sclerosis complex case report conclusion patients significant intellectual disability prevents maintaining conscious cooperation require rrt must individually adjusted therapy case presented patient decided perform preemptive kidney transplantation determined father,0.0
anticd20 immunotherapy progressive multiple sclerosis 2year realworld followup 108 patients conclusion large cohort confirms tolerance treatments realworld setting standardized clinical assessments improve detection deteriorating patients studies needed establish predictive factors,0.0
cellular senescence aging brain promising target neurodegenerative diseases aging inevitable along reduced ability maintain homeostasis various biological processes aging gradually deteriorates overall health extensive research aging brain identified cellular senescence critical risk factor neurodegeneration cognitive decline associations cellular senescence neurodegenerative diseases like alzheimers disease syndrome parkinsons disease multiple sclerosis evident extensive body literature,0.0
risk fingolimod rebound switching cladribine rituximab multiple sclerosis abstractbackground sudden onset extensive disease activity including severe clinical relapse extensive brain spinal magnetic resonance imaging mri lesions termed rebound disease activity reported withdrawal fingolimod patients multiple sclerosis ms objective compare risk rebound switching fingolimod cladribine rituximab msmethods patients switching fingolimod cladribine rituximab included retrospective cohort study utilizing prospectively collected data two university hospitals different treatment strategiesresults total 73 patients least 6 months followup switching identified 33 patients switched fingolimod cladribine 40 patients rituximab patients rituximab group seven 211 cladribine group qualified rebound disease activity ten 303 patients using cladribine five 125 patients using rituximab experienced relapse mri disease activity seen 18 545 eight 200 patients using cladribine rituximab respectively younger age previous high relapse rate associated increased risk rebound cladribine groupconclusions identify lower risk rebound first year switching fingolimod rituximab compared cladribine indicating better initial clinical outcome former treatment strategy,0.0
home treatment fatigue multiple sclerosis personalized bilateral wholebody somatosensory cortex stimulation abstractbackground fatigue multiple sclerosis ms highly invalidating symptom pharmacological efficacious therapies furthermore present frequent severe side effects two previous randomized controlled trials observed efficacy personalized neuromodulation treatment consisting personalized transcranial direct current stimulation tdcs 15 minutes per day 5 days faremus methods medicaldevice phase ii study aimed assessing feasibility acceptance safety efficacy faremus treatment applied patients home considered efficacy primary outcome assessed reduction fatigue levels measured modified fatigue impact scale mfis scored treatment primary outcome determined sample size estimate individual adhoc questionnaires quantified acceptance safety side effects treatmentresults 15 patients completed treatment reporting optimal acceptance safety using faremus home without sideeffects treatment ameliorated fatigue symptoms 20 baseline 10 15 patients 37 average corresponding effect size 121conclusions faremus personalized electroceutical intervention 5days anodal tdcs bilateral wholebody somatosensory cortex well accepted can feasibly safely efficaciously applied patients home offering comfortable treatment reducing need travel fatiguerelated symptoms hamper quality life,0.0
short report reallife analysis occurrence persistent transient fluctuating positive titres neutralizing antidrug antibodies multiple sclerosis patients treated interferon beta abstractinterferon beta ifn first line therapy treatment multiple sclerosis ms however 47 treated patients will develop neutralising antidrug antibodies nabs ifn high titres can inhibit therapeutic effect drug study aimed determine frequency transient fluctuating nab positivity realworld clinical routine setting using large retrospective international cohort ifntreated ms collected part abirisk consortium n 9657 transient fluctuating nabs rare 26 09 respectively bring noteworthy considerations clinical decisions context nabs,0.0
adherence subcutaneous interferon beta1a multiple sclerosis patients receiving periodic feedback drug use discussion readouts rebismartsup sup injector results prospective cohort study rebiflect conclusion treatment adherence rebismart device generally high consistent noninterventional studies first reflection talk supported rebismart induces excellent adherence stabilized repetition reflection patients subcutaneous interferon beta1a treatment monitored rebismart recommended ensure prolonged strong treatment adherence,0.0
realworld effectiveness safety fingolimod patients multiplesclerosis czech republic results core extension parts golems study 48months conclusion golems study demonstrated sustained effectiveness manageable safety profile fingolimod realworld conditions 48 months patients ms,0.0
early predictors clinical mri outcomes using lasso multiple sclerosis objective identify predictors common different clinical mri outcomes multiple sclerosis ms comparing predictive models,0.0
optical coherence tomography retinal imaging biomarker neuroinflammation neurodegeneration systemic disorders adults children retina optic nerve considered extensions central nervous system cns thus can serve window evaluation cns disorders spectral domain optical coherence tomography oct allows detailed evaluation retina optic nerve oct can noninvasively document changes single retina layer thickness structure due neuronal retinal glial cells rgc modifications systemic local inflammatory neurodegenerative diseases can,0.0
fatigue depression anxiety among ambulating multiple sclerosis patients conclusion current study shows depression anxiety fatigue tend correlated clustered together among pwms cohort however fatigue associated intensity physical activity undertaken results study important improvement clinical management ms patients,0.0
postural sway parkinsons disease multiple sclerosis patients tasks different complexity neurological diseases associated static postural instability differences postural sway neurological diseases include conceptual information certain symptoms affect static postural stability information might potential become helpful aid process finding appropriate treatment training program therefore study investigated static postural sway performance parkinsons disease pd multiple sclerosis,0.0
mouse models immune dysfunction neuroanatomical differences reflect anxietybehavioural phenotype extensive evidence supports role immune system modulating brain function behaviour however past studies revealed striking heterogeneity behavioural phenotypes produced immune system dysfunction using magnetic resonance imaging studied neuroanatomical differences among 11 distinct genetically modified mouse lines n 371 deficient different element immune system found significant heterogeneous effect immune dysfunction,0.0
longitudinal tracking axonal loss using diffusion magnetic resonance imaging multiple sclerosis axonal loss cns key driver progressive neurological impairments people multiple sclerosis currently established methods tracking axonal loss clinically study aimed determine sensitivity longitudinal diffusion mriderived fibrespecific measures axonal loss people multiple sclerosis fibre measures derived diffusion mri acquired part standard radiological mri protocol compared establish measures,0.0
hereditary gynecologic cancer syndromes narrative review hereditary cancer syndromes defined syndromes genetics cancer result low penetrant polymorphisms single gene disorder inherited mendelian fashion last decade compelling evidence accumulated approximately 510 cancers attributed hereditary cancer syndromes tremendous progress made last decade evaluation management syndromes however hereditary syndromes associated,0.0
contribution neuropathology multiple sclerosis research conclusions results studies highly relevant identification potential therapeutic targets ms patients design pivotal clinical trials,0.0
incidence developmental venous anomalies patients multiple sclerosis 3 tesla mri study conclusions frequency dva ms patients comparable controls whether dva size appearance may change time will investigated longitudinal manner larger sample size,0.0
french version short form neurogenic bladder symptom score crosscultural adaptation validation conclusions psychometric qualities french version nbsssf wellsupported thus providing valid tool measure bladder symptoms across three different domains patients neurogenic bladder,0.0
internuclear ophthalmoplegia characterizes multiple sclerosis rather neuromyelitis optica spectrum disease conclusions study shows incidence new ino 38 vs 239 per 1 000 person years odds ino time point significantly lower nmosd ms suggests ino consequently mlf lesions less common nmosd presence ino may help differentiation nmosd ms may aid earlier implementation disease appropriate therapy,0.0
comorbidities predictors allcause emergency department utilization among veterans multiple sclerosis abstractbackgroundwhile comorbidities associated allcause hospitalizations among persons multiple sclerosis ms examination role allcause emergency department ed utilization study aimed determine presence comorbidities increases odds ed usage national sample veterans msmethodsdata extracted retrospectively veterans affairs va ms center excellence data repository electronic health recordbased dataset veterans least one outpatient visit 2013 alive 2015 initially prescribed disease modifying therapy included dataset n3 742 current procedural terminology codes used determine participants least one ed visit 24month time frame beginning 1 1 2013 comorbidities identified using icd9 codes present 2013 separate logistic regressions conducted overall number comorbidities categorized comorbidities adjusting age race sexresultsnearly 32 n1 191 least one ed visit veterans average 667 sd332 comorbidities adjusting demographics number comorbidities significant predictor ed usage aor120 95 ci 117 123 p001 several comorbidities emerged independent contributorsconclusionsallcause ed utilization prevalent ms usage increasing presence chronic conditions findings underscore need view longterm ms care lens chronic disease management,0.0
comorbidities predictors allcause emergency department utilization among veterans multiple sclerosis abstractbackground comorbidities associated allcause hospitalizations among persons multiple sclerosis ms examination role allcause emergency department ed utilization study aimed determine presence comorbidities increases odds ed usage national sample veterans msmethods data extracted retrospectively veterans affairs va ms center excellence data repository electronic health recordbased dataset veterans least one outpatient visit 2013 alive 2015 initially prescribed disease modifying therapy included dataset n3 742 current procedural terminology codes used determine participants least one ed visit 24month time frame beginning 1 1 2013 comorbidities identified using icd9 codes present 2013 separate logistic regressions conducted overall number comorbidities categorized comorbidities adjusting age race sexresults nearly 32 n1 191 least one ed visit veterans average 667 sd332 comorbidities adjusting demographics number comorbidities significant predictor ed usage aor120 95 ci 117 123 p001 several comorbidities emerged independent contributorsconclusions allcause ed utilization prevalent ms usage increasing presence chronic conditions findings underscore need view longterm ms care lens chronic disease management,0.0
fractional anisotropy helps differentiate optic nerve impairment neuromyelitis optica spectrum disorders multiple sclerosis conclusion fa quantify characteristics nmosd msrelated optic nerve impairment dti simple effective imaging tool differentiate two,0.0
oscillatory calcium release sustained storeoperated oscillatory calcium signaling prevents differentiation human oligodendrocyte progenitor cells endogenous remyelination demyelinating diseases multiple sclerosis contingent upon successful differentiation oligodendrocyte progenitor cells opcs signaling via g q coupled muscarinic receptor m 1 3 r inhibits human opc differentiation impairs endogenous remyelination experimental models hypothesized calcium release following g q coupled receptor g q r activation directly regulates human opc hopc cell fate study show,1.0
evaluation psychometric properties health assessment questionnaire haq population individuals multiple sclerosis introduction health assessment questionnaire haq translated many languages classified predictor disability medical costs however psychometric properties haq never studied population neurological disease purpose study evaluation psychometric properties haq population individuals multiple sclerosis ms,0.0
covid19 outcomes myasthenia gravis patients analysis electronic health records united states conclusions covid19 patients mg likely admitted hospital require icu care older age patients dysphagia increased risk mortality,0.0
challenges opportunities realworld data statistical analysis plan optimisems multicenter prospective cohort pharmacovigilance study conclusion optimisems expected rich source data outcomes dmts realworld conditions several years followup inclusive sample uk ms patients analysis complicated influence confounding factors including complex treatment histories highly variable disease course statistical analysis plan includes measures mitigate biases factors can introduce will enable us address key questions beyond reach,0.0
neurogenerative disease diagnosis cepstral domain using mfcc deep learning underlying cognitive neuromuscular activities regulate speech signals biomarkers human voice can provide insight neurological illnesses multiple motor nonmotor aspects neurologic voice disorders arise underlying neurologic condition parkinsons disease multiple sclerosis myasthenia gravis als voice problems can caused disorders affect corticospinal system cerebellum basal ganglia upper lower motoneurons according,0.0
multiple sclerosisrelated fatigue lacks unified definition narrative review fatigue common symptom multiple sclerosis ms although msrelated fatigue msf strongly affects quality life social performance patients currently lack knowledge pathophysiology turns leads poor objective diagnosis management recent studies attempted explain potential etiologies well treatments msf however seems without consensus nature data provide route,0.0
phase ii study ketogenic diets relapsing multiple sclerosis safety tolerability potential clinical benefits conclusion kds safe tolerable 6month study period yield improvements body composition fatigue depression qol neurological disability adiposerelated inflammation persons living relapsing ms,0.0
neurophysiological behavioural correlates ocrelizumab therapy manual dexterity patients primary progressive multiple sclerosis conclusion intracortical sensorimotor networks involved hand dexterity dysfunction ppms ocrelizumab therapy displays beneficial effect hand dexterity impairment likely intracortical networks implicated fast sensorimotor integration,0.0
effectiveness acupuncture multiple sclerosis protocol systematic review metaanalysis conclusion study will perform comprehensive systematic review metaanalysis efficacy acupuncture ms making lack relevant evidence clinical use acupuncture,0.0
safety monitoring treatment diseasemodifying therapies multiple sclerosis background diseasemodifying therapies dmts multiple sclerosis ms widely used given proven efficacy relapsing form disease recently siponimod ocrelizumab approved progressive forms disease currently 22 diseasemodifying drugs approved fda 2012 nine market march 2019 august 2020 six new drugs approved rapid development new dmts highlights need update,0.0
immunopathology tumefactive demyelinating lesionsfrom idiopathic drugrelated cases tumefactive demyelinating lesions tdl represent diagnostic dilemma clinicians rare atypical cases collaboration neuroradiologist neurologist neuropathologist warranted accurate diagnosis recent advances neuropathology shown tdl represent umbrella many different diagnostic entities can responsible tdl can emerge part spectrum classic multiple sclerosis ms also can represent idiopathic,1.0
economic burden multiple sclerosis united states estimate direct indirect costs background objectives recent report estimated approximately one million adults living multiple sclerosis ms united states us ms rarely direct cause death debilitating effects normal body functions can result considerable disruption daily living life roles including work physical independence mobility social interaction participation leisure activities study estimated total economic burden ms us,0.0
evaluation surrogate endpoints using informationtheoretic measure association based havrda charvat entropy surrogate endpoints used assess efficacy treatment can potentially reduce duration number required patients clinical trials using information theory alonso et al 2007 proposed unified framework based shannon entropy new definition surrogacy departed hypothesis testing framework paper new family surrogacy measures havrda charvat hc entropy derived contains alonsos definition,0.0
costutility analysis teriflunomide nave vs previously treated patients relapsingremitting multiple sclerosis italy conclusion teriflunomide rrms nave vs experienced patients costeffective possibly strongly dominant healthcare sector society viewpoints italy findings need confirmation realworld studies,0.0
understanding magnetic resonance imaging multiple sclerosis umims development piloting online education program magnetic resonance imaging people multiple sclerosis conclusion satisfaction program good mririsk knowledge usage demonstrates need applicability ebpi mri ms,0.0
complex interplay trait fatigue cognition multiple sclerosis cognitive impairments frequent patients multiple sclerosis ms yet influence msrelated symptoms cognitive status clear studies investigating impact trait fatigue along anxiodepressive symptoms cognition seldom even less considered fatigue multidimensional moreover studies provided conflicting results twentynine ms patients 28 healthy controls matched age gender education underwent full comprehensive,0.0
role b cells interactions stromal cells context inflammatory autoimmune diseases interactions b cells stromal cells essential functions immune cell development responses chronic inflammation proinflammatory microenvironment leads changes stromal cells acquire pathogenic phenotype specific organ disease b cells recruited site inflammation interact pathogenic stromal cells contributing diseases severity addition producing autoantibodies b cells contribute,0.0
nfat5 contributes pathogenesis experimental autoimmune encephalomyelitis eae decrease t regulatory cells female mice multiple sclerosis disproportionally affects women present study undertaken determine whether nfat5 contributed pathogenesis experimental autoimmune encephalomyelitis eae model multiple sclerosis whether impact sex associated nfat5 haplodeficiency reduced disease severity female mice effect associated significant increases frequency t regulatory treg cells cns 145 039 373 094,0.0
consensus paper ataxic gait aim consensus paper discuss roles cerebellum human gait well assessment therapy cerebellar vermis critical postural control cerebellum ensures mapping sensory information temporally relevant motor commands mental imagery gait involves intrinsically connected frontoparietal networks comprising cerebellum muscular activities cerebellar patients show impaired timing discharges affecting patterning,0.0
brainstem connectome database connectivity data nervous system subdivisions brainstem cerebral cortex subcortical nuclei necessary understand connectional structures predict effects connectional disorders simulate network dynamics purpose database built analyzed comprises known directed weighted connections within rat brainstem longterm metastudy original research publications describing tract tracing results form foundation,0.0
brain virtual histology xray phasecontrast tomography part wholebrain myelin mapping whitematter injury models whitematter injury leads severe functional loss many neurological diseases myelin staining histological samples common technique investigate whitematter fibers however tissue processing sectioning may affect reliability 3d volumetric assessments purpose study propose approach enables myelin fibers mapped whole rodent brain microscopic resolution without need strenuous staining aim,1.0
peripheral b cell dysregulation associated relapse longterm quiescence multiple sclerosis patients b cells play major role multiple sclerosis ms many successful therapeutics capable removing circulation one therapy alemtuzumab thought reset immune system without need ongoing therapy proportion patients exact cells contributing disease pathogenesis quiescence remain identified utilised mass cytometry analyse b cells blood relapseremitting ms rrms patients alemtuzumab treatment,0.0
negative interpretation ambiguous bodily information patients relapsingremitting multiple sclerosis abstractrelapsingremitting ms rrms characterised patients experience periods exacerbation symptoms fear associated relapse influence quality life patients relationship bodily experiences previous studies suggested health anxiety ha contributes fear relapse investigated cognitive mechanisms involved developing maintaining fear relapse patients interested test relationship used online interpretation paradigm investigate biased interpretation ambiguous bodily information relationship ha among patients healthy controls 65 subjects group patients higher levels ha controls patients also interpreted ambiguous bodily information negatively controls significant positive correlation ha negative interpretation information whole sample among patients ha mediated relationship interpretation bias fear relapse findings study suggest negative interpretation bias can contribute higher ha turn contributed fear relapse among patients rrms findings important implications improving quality life patients suffering ms,0.0
negative interpretation ambiguous bodily information patients relapsingremitting multiple sclerosis abstractrelapsingremitting ms rrms characterised patients experience periods exacerbation symptoms fear associated relapse influence quality life patients relationship bodily experiences previous studies suggested health anxiety ha contributes fear relapse investigated cognitive mechanisms involved developing maintaining fear relapse patients interested test relationship used online interpretation paradigm investigate biased interpretation ambiguous bodily information relationship ha among patients healthy controls 65 subjects group patients higher levels ha controls patients also interpreted ambiguous bodily information negatively controls significant positive correlation ha negative interpretation information whole sample among patients ha mediated relationship interpretation bias fear relapse findings study suggest negative interpretation bias can contribute higher ha turn contributed fear relapse among patients rrms findings important implications improving quality life patients suffering ms,0.0
trpv2 key player myelination disorders central nervous system transient potential receptor vanilloid 2 trpv2 widely expressed nervous system specifically found neuronal subpopulations glial cells trpv2 known sensitized methionine oxidation results inflammation aim characterize expression regulation trpv2 myelination pathologies hypomyelination demyelination validated interaction trpv2 putative interactor opalin oligodendrocyte,1.0
cell differentiation proliferation bone marrow organs 2d2 mice spontaneous development eae leading production abzymes exact cellular molecular mechanisms multiple sclerosis autoimmune diseases established autoimmune pathologies known associated faults immune system changes differentiation profiles bone marrow stem cells study analyzed various characteristics experimental autoimmune encephalomyelitis eae 2d2 mice differentiation profiles six hematopoietic stem cells bone marrow found significantly differ 2d2,0.0
association latitude exposure ultraviolet b radiation severity multiple sclerosis international registry study background objectives severity multiple sclerosis ms varies widely among individuals understanding determinants heterogeneity will help clinicians optimize management ms aim study investigate association latitude residence ultraviolet b radiation exposure uvb severity ms,0.0
covid19 severity associated reduction tlymphocytes anticd20treated people multiple sclerosis neuromyelitis optica spectrum disorder abstract,0.0
effects latitude sunlight multiple sclerosis severity two peas pod abstract,0.0
molecular basis pathophysiology trigeminal neuralgia trigeminal neuralgia tn complex orofacial pain syndrome characterized paroxysmal onset pain attacks trigeminal distribution underlying mechanism debilitating condition still clearly understood decades basic clinical evidence support demyelination hypothesis demyelination along trigeminal afferent pathway major driver tn pathogenesis pathophysiology pathological demyelination can triggered physical,1.0
effects mediated dimethyl fumarate vitro oligodendrocytes implications multiple sclerosis conclusions results obtained confirm dmf antiinflammatory antioxidant effects also oli neu cells interestingly appears promote olcs differentiation towards mature potentially myelinating cells,1.0
use robotic devices gait training patients diagnosed multiple sclerosis current state art multiple sclerosis ms neurodegenerative disease produces alterations balance gait patients robotassisted gait training devices proposed complementary approach conventional rehabilitation treatment means improving alterations aim study investigate available scientific evidence benefits use robotics physiotherapy treatment people ms systematic review randomized controlled,0.0
predictors severe illness children multisystem inflammatory syndrome sarscov2 infection multicentre cohort study background sarscov2 infection can lead multisystem inflammatory syndrome children misc sought investigate risk factors admission intensive care unit icu explored changes disease severity time,0.0
longterm treatment anticd20 monoclonal antibodies untenable risk yes abstract,0.0
systematic review extracorporeal shock wave therapy botulinum toxin spasticity treatment comparison efficacy conclusions beneficial effect spasticity found treatments evidence showed eswt bonta can ameliorate spasticity considering parameters mas mts arom prom uefma vas sfs poststroke multiple sclerosis cerebral palsy patients research required strengthen evidence suitable study protocols highly needed,1.0
mapping neuroinflammationinduced hypoxia spinal cord using optoacoustic imaging recent studies suggest metabolic changes oxygen deficiency central nervous system play important role pathophysiology multiple sclerosis ms present study investigated changes oxygenation analyzed vascular perfusion spinal cord rodent model ms performed multispectral optoacoustic tomography lumbar spinal cord oxygen enhancement challenge mice experimental autoimmune encephalomyelitis,0.0
menstrual bloodderived mesenchymal stromal cells efficiently ameliorate experimental autoimmune encephalomyelitis inhibiting t cell activation mice conclusions data demonstrate readily available mbmscs significantly reduced disease severity eae upon transplantation thus potential developed readytouse allomscs msrelated inflammation,0.0
evaluation muscle synergy exoskeletonassisted walking persons multiple sclerosis conclusion exoskeletonassistance alter existing synergy modules induce new module emerge alters control modules ie modifies neural commands indicated reduced amplitude activation profiles,0.0
structural insights sphingosine1phosphate receptor activation significancesphingosine1phosphate s1p receptors valid therapeutic targets treat autoimmune diseases relapsing multiple sclerosis ulcerative colitis particularly s1pr1 well characterized nonredundant functions t b cells egress however activation mechanism s1pr1 still poorly understood therefore determined active s1pr1g complex structures bound distinct agonists phosphorylated fingolimod s fty720p modulate,0.0
nutritional nonnutritional strategies bodybuilding impact kidney function bodybuilders routinely engage many dietary practices purported harmful kidney health development acute kidney injury focal segmental glomerular sclerosis fsgs nephrocalcinosis may particular risks little evidence highprotein diets moderate creatine supplementation pose risks individuals normal kidney function though longterm high protein intake underlying impairment kidney function inadvisable links,0.0
evaluating impact regional studentled physiotherapy clinic model improve selfreported function communitydwelling adults neurological diagnoses background purpose neurological conditions major cause health morbidity negatively impacts function quality life qol despite burden community services disproportionally scarce studentled physiotherapy services slss model can increase community access health care providing authentic clinical experiences students slss consistently demonstrate high client satisfaction however limited evaluation impact model,0.0
pharmacological targeting sphingosine kinases impedes hiv1 infection cd4 t cells samhd1 modulation sphingosine1phosphate s1p sphingolipid modulator myriad cellular processes therapeutic targeting s1p signaling utilized clinically treat multiple sclerosis previously shown functional antagonism s1p receptors reduces cellfree celltocell latent hiv1 infection primary cd4 t cells work examined whether targeting sphingosine kinase 1 2 sphk1 2 inhibit s1p production prevent infection using multiple hiv1 primary,0.0
current insights role fli1 hematopoiesis malignant transformation fli1 member ets family transcription factors discovered 1991 retroviral insertional mutagenesis driver mouse erythroleukemias past 30 years nearly 2000 papers defined biology impact normal development cancer hematopoietic system fli1 controls selfrenewal stem cells differentiation diverse mature blood cells fli1 also controls endothelial survival vasculogenesis high low levels fli1,0.0
essential protective role catalytically active antibodies abzymes redox antioxidant functions animals humans life aerobic organisms oxygen resulting numerous reactions converted reactive oxygen species ros many ros dangerous due high reactivity strong oxidants react various cell components leading damage protect ros overproduction enzymatic nonenzymatic systems evolved aerobic cells several known nonenzymatic antioxidants relatively low specific antioxidant activity superoxide dismutases,0.0
relaxation related therapies people multiple sclerosis ms systematic review conclusion emerging evidence relaxation therapies can improve outcomes persons multiple sclerosis given high risk bias found included studies stronger conclusions drawn,0.0
author response burden sepsis critically ill patients multiple sclerosis populationbased cohort study abstract,0.0
mesenchymal stem cellderived extracellular vesicles therapeutic use central nervous system demyelinating disorders autoimmune demyelinating diseasesincluding multiple sclerosis neuromyelitis optica spectrum disorder antimyelin oligodendrocyte glycoproteinassociated disease acute disseminated encephalomyelitis glial fibrillary acidic protein gfap associated meningoencephalomyelitisare heterogeneous group diseases even though common pathology characterized neuroinflammation loss myelin reactive astrogliosis lack safe pharmacological therapies purported,1.0
long term persistence sarscov2 humoral response multiple sclerosis subjects abstractbackground objectivesthe persistence severe acute respiratory syndrome coronavirus sarscov 2 pandemic partly due appearance highly infectious variants made booster vaccinations necessary vulnerable groups present data regarding decline sarscov2 bnt162b2 mrna vaccineinduced humoral immune response monocentric cohort ms patientsmethods96 ms patients undergoing eight different dmts without previous sarscov2 infection evaluated antispike igg levels 21 days t1 56 months t2 second sarscov2 bnt162b2 mrna vaccine dose antispike igg titre ms subjects compared 21 age sexmatched healthy controls hc resultswhen compared sarscov2 igg levels t2 hc observed comparable levels interferon 1a dimethyl fumarate teriflunomide natalizumabtreated ms subjects impaired humoral response ms subjects undergoing glatiramer acetate cladribine fingolimod ocrelizumabtreatments moreover comparison sarscov2 igg spike titre t1 t2 revealed faster decline humoral response patients undergoing dimethyl fumarate interferon 1a glatiramer acetatetherapies receiving teriflunomide natalizumab showed higher persistence compared healthy controlsconclusionthe prominent decline humoral response ms subjects undergoing dimethyl fumarate interferon 1a glatiramer acetatetherapies considered formulating booster regimens subjects benefit early booster vaccinations,0.0
long term persistence sarscov2 humoral response multiple sclerosis subjects abstractbackground objectivesthe persistence severe acute respiratory syndrome coronavirus sarscov 2 pandemic partly due appearance highly infectious variants made booster vaccinations necessary vulnerable groups present data regarding decline sarscov2 bnt162b2 mrna vaccineinduced humoral immune response monocentric cohort ms patientsmethods96 ms patients undergoing eight different dmts without previous sarscov2 infection evaluated antispike igg levels 21 days t1 56 months t2 second sarscov2 bnt162b2 mrna vaccine dose antispike igg titres ms subjects compared 21 age sexmatched healthy controls hc resultswhen compared sarscov2 igg levels t2 hc observed comparable levels interferon 1a dimethyl fumarate teriflunomide natalizumabtreated ms subjects impaired humoral response ms subjects undergoing glatiramer acetate cladribine fingolimod ocrelizumabtreatments moreover comparison sarscov2 igg spike titre t1 t2 revealed faster decline humoral response patients undergoing dimethyl fumarate interferon 1a glatiramer acetatetherapies receiving teriflunomide natalizumab show higher persistence compared healthy controlsconclusionthe prominent decline humoral responses ms subjects undergoing dimethyl fumarate interferon 1a glatiramer acetatetherapies considered formulating booster regimens subjects benefit early booster vaccinations,0.0
disease modifying therapy switching relapsing multiple sclerosis delphi consensus demyelinating expert group spanish society neurology abstractbackground increase available disease modifying therapies dmts multiple sclerosis led greater emphasis improving treatment sequencing paradigms article summarises opinions panel 25 experts treatment switching approaches relapsing multiple sclerosis rms methods modified delphi consensus process carried develop clinically relevant statements aiding treatment decisions patients rms 16th january 9th october 2019 subgroup two experts core group carried extensive review literature formulated 106 statements expert panel evaluateresults total number 106 statements submitted expert panel critical evaluation consensus least 80 panelists agreed reached 99 statements cover treatment objectives reasons dmt switching suboptimal response criteria strategies treatment change washout periodsconclusion agreed statements provide uptodate guidance dmt sequencing optimal patient management,1.0
exploring recent trends management dementia frailty focus diagnosis treatment dementia frailty increase health adversities older adults topics growing research interest frailty considered correspond biological syndrome associated age frail patients may ultimately develop multiple dysfunctions across several systems including stroke transient ischemic attack vascular dementia parkinsons disease alzheimers disease frontotemporal dementia dementia lewy bodies corticobasal degeneration multiple system atrophy,0.0
pediatric multiple sclerosis developments timely diagnosis prognostication introduction pediatriconset po multiple sclerosis ms accounts 210 total ms cases recently greater attention given poms substantial improvements understanding pathophysiology diagnostic workup identification reliable prognosticators associated longterm disability patients,0.0
current standing autologous haematopoietic stem cell transplantation treatment multiple sclerosis autologous haematopoietic stem cell transplantation ahsct gaining traction valuable treatment option patients affected severe multiple sclerosis ms particularly relapsingremitting form describe current literature terms clinical trials observational retrospective studies well immune reconstitution following transplantation focus conditioning regimens used transplantation evidence base predominantly consists,0.0
critical review ozanimod treatment adults moderately severely active ulcerative colitis introduction ozanimod sphingosine1phosphate s1p modulator inhibits lymphocyte trafficking lymph nodes circulation approved us food drug administration fda treatment relapsing multiple sclerosis recently management moderatesevere ulcerative colitis uc,0.0
identifying prospective memory deficits multiple sclerosis preliminary evaluation criterion ecological validity single item version memory intentions test mist objectives difficulties prospective memory pm routinely assessed persons multiple sclerosis ms even though can impact daily functioning study aimed examine preliminary criterion ecological validity highly abbreviated memory intentions test mist intended serve initial screening pm persons ms methods participants n 112 classified impaired performed 15 standard deviations normative mean,0.0
realworld outcomes teriflunomide relapsingremitting multiple sclerosis prospective cohort study conclusions results support efficacy tolerability teriflunomide treatmentnave rrms patients realworld practice female patients patients less relapses less disability treatment likely benefit teriflunomide treatment,0.0
examining relationship reactive stepping outcomes falls people multiple sclerosis conclusion people ms history falling show delayed step onsets backward reactive stepping specifically every 10 milliseconds increase step latency people ms 25 times likely fall history although clinical trials necessary determine whether interventions targeting reactive stepping reduce falls people ms current work indicates latency steps may relevant target work,0.0
framework efficient nway interaction testing case control studies categorical data goal common diseases influenced multiple gene interactions interactions environment performing exhaustive search identify interactions computationally expensive needs address multiple testing problem fourstep framework proposed efficient identification nway interactions methods framework applied multiple sclerosis dataset 725 subjects 147 tagging snps first two steps framework quality,0.0
evaluation humoral cellular responses sarscov2 mrna vaccinated immunocompromised patients conclusion patients acquired inherited immune disorders may show variable immune responses vaccination bnt162b2 mrna vaccine sarscov2 whether humoral cellular immune responses delayed depends patient group therapy individual risk factors data may guide counselling patients immune disorders regarding vaccination sarscov2,0.0
kappa free light chains soluble interleukin2 receptor interleukin6 help explore patients presenting brain white matter hyperintensities introduction many patients referred multiple sclerosis ms tertiary centers manage brain white matter hyperintensities wmh multiple diagnoses can match situations lack proper tools diagnose complex cases,0.0
applied bayesian approaches research motor neuron disease statistical evaluation empirical data basis modern scientific method available tools include various hypothesis tests specific data structures well methods used quantify uncertainty obtained result statistics pivotal many misconceptions arise due complexity difficulttoacquire mathematical background even though studies rely frequentist interpretation statistical readouts application bayesian,0.0
serum 25 oh vitamin d level relapsingremitting multiple sclerosis clinically isolated syndrome groups conclusions since vitamin d deficiency poses problem early stage disease spectrum cis patients ms patients 25 oh vitamin d level routinely controlled replacement administered upon deficiency state,0.0
emtn emp peptide suppresses experimental autoimmune encephalomyelitis eae preclinical mouse model tnp family patented synthetic peptides preclinical development stage valuable potential therapeutic indication multiple sclerosis ms autoimmune demyelinating disease central nervous system cns use preclinical animal model experimental autoimmune encephalomyelitis eae deepened knowledge immunomodulatory functions tnp drug shown tnp possesses disease suppressive function eae ameliorating,1.0
efficacy safety abobotulinumtoxina patients neurogenic detrusor overactivity incontinence performing regular clean intermittent catheterization pooled results two phase 3 randomized studies content1 content2 conclusions intradetrusor abobonta effective treatment alternative option patients ndoi inadequate response oral anticholinergics already performing cic,0.0
tenascinc fibrosis multiple organs translational implications systemic sclerosis ssc scleroderma complex disease pathogenic triad autoimmunity vasculopathy fibrosis involving skin multiple internal organs 1 fibrosis accounts much 45 deaths worldwide appears increasing prevalence 2 understanding pathogenesis progression urgent scientific challenge fibroblasts myofibroblasts key effector cells executing physiologic tissue repair one hand,0.0
olfactory dysfunction reflects disease progression japanese patients multiple sclerosis objective olfactory dysfunction important clinical feature patients multiple sclerosis ms incidence extent olfactory dysfunction reportedly higher secondary progressive sp ms relapsing remitting rr ms investigated use olfactory dysfunction evaluating disease status japanese patients ms methods olfactory identification evaluated using odor stick identification test japanese ositj patients,0.0
undertaking specific stressreducing activities associated reduced fatigue depression increased mastery people multiple sclerosis abstractbackgroundmultiple sclerosis demyelinating autoimmune disease presenting heterogenous symptoms impact daily living undertaking stressreducing activities may reduce symptoms including depression fatigue enhance mastery sense control ones life assessed crosssectional associations undertaking stressreducing activities meditation depression fatigue mastery 5year prospective relationships meditation outcomesmethodsdata extracted longitudinal health outcomes lifestyle sample people multiple sclerosis holism study stressreducing activities categorised relaxation physical mindbody spiritual meditation analysed dichotomous term duration frequency practice depression fatigue mastery assessed patients health questionnaire9 fatigue severity scale pearlin mastery scale respectively associations depression fatigue mastery assessed logbinomial regression models adjusted age sex symptoms due relapse socioeconomic status employment status antidepressant antifatigue medication use appropriateresultscrosssectionally physical relaxation activities associated 40 33 lower frequencies depression respectively physical activities additionally associated 19 lower frequency fatigue meditation associated 30 lower frequency depression 17 higher mastery prospectively meditation associated 28 decreased depression 48 reduction developing depression 5year followupconclusionpotential benefits undertaking stressreducing activities meditation depression fatigue mastery promising assessed prospectively meditation practice encouraged safe inexpensive intervention prevention depression,1.0
undertaking specific stressreducing activities associated reduced fatigue depression increased mastery people multiple sclerosis abstractbackground multiple sclerosis ms demyelinating autoimmune disease presenting heterogenous symptoms impact daily living undertaking stressreducing activities may reduce symptoms including depression fatigue enhance mastery sense control ones life assessed crosssectional associations undertaking stressreducing activities meditation practice depression fatigue mastery 5year prospective relationships meditation outcomesmethods data extracted longitudinal health outcomes sample people multiple sclerosis holism study stressreducing activities categorised relaxation physical mindbody spiritual meditation analysed dichotomous term duration frequency practice depression fatigue mastery assessed patients health questionnaire9 fatigue severity scale pearlin mastery scale respectively associations depression fatigue mastery assessed logbinomial regression models adjusted age sex symptoms due relapse socioeconomic status employment status antidepressant antifatigue medication use appropriateresults crosssectionally physical relaxation activities associated 40 33 lower frequencies depression respectively physical activities additionally associated 19 lower frequency fatigue meditation associated 30 lower frequency depression 17 higher mastery prospectively meditation associated 28 decreased depression 48 reduction developing depression 5year followupconclusion potential benefits undertaking stressreducing activities meditation depression fatigue mastery promising assessed prospectively meditation practice encouraged safe inexpensive intervention prevention depression,1.0
advanced diffusionweighted imaging models better characterize white matter neurodegeneration clinical outcomes multiple sclerosis conclusion voxelbased fcs able detect wm tracts atrophy ms clinical phenotypes greater anatomical specificity compared measures volumetric dtderived measures wm damage fcs v ic measured baseline wm best predictors clinical disability cognitive impairment,0.0
glibenclamidesensitive trpm4mediated component ca1 excitatory postsynaptic potentials appears experimental autoimmune encephalomyelitis transient receptor potential melastatin 4 trpm4 channel contributes disease severity murine experimental autoimmune encephalomyelitis eae model multiple sclerosis neuronal cell death models excitotoxicity traumatic brain injury trpm4 activated intracellular calcium conducts monovalent cations hypothesized trpm4 may contribute boost excitatory synaptic transmission ca1 pyramidal neurons hippocampus using singlespine,0.0
brain atrophy patterns multiple sclerosis patients treated natalizumab clinical correlates conclusion atrophy rrms patients treated ntz regional targeting highly cognitive regions mainly subcortical gray matter cerebellum cerebellum atrophy marker physical disability progression ntz accelerate atrophy process ms may play neuroprotective role increasing thalamus volume,1.0
psoriasis caused ocrelizumab two persons primary progressive multiple sclerosis abstract,0.0
role cholesterol metabolism multiple sclerosis molecular pathophysiology radiological clinical disease activity multiple sclerosis ms chronic inflammatory disease cns leading demyelination axonal degeneration increasing body evidence suggests lipid metabolism associated adverse clinical mri outcomes ms review summarize findings association lowdensity lipoproteins ldl highdensity lipoproteins hdl apolipoproteins oxysterols clinical radiological disease activity ms although causality disease,1.0
challenges longitudinal characterization lower urinary tract dysfunction multiple sclerosis abstractbackgroundneurogenic lower urinary tract dysfunction lutd results lower urinary tract symptoms luts impact quality life people multiple sclerosis pwms risk factors contribution lutd multiple sclerosis ms disease progression underresearchedobjectiveto identify clinical demographic predictors luts pwms gaps clinical ascertainmentmethodsparticipants adults ms enrolled prospective multicenter study summit n802 including subset n258 patients ucsf epic study medical records reviewed demographic age sex race ethnicity clinical disease duration ms type femalespecific reproductive factors eg parity evaluated determine associations bowel bladder functional system scores participants medical records analyzed understand patterns luts ascertainment physicians specific contribution luts overall bowel bladder functional system scoresresults802 participants 713 female contributed analyses higher bowel bladder functional system scores indicating worsening symptoms function significantly associated female sex p0001 progressive ms type p 0001 epic participants femalespecific reproductive exposures parity menopause significantly associated worse bowel bladder fs scores 98 bowel bladder functional system scores reflected severity luts relative bowel dysfunction luts underascertained clinically women x2502 p008 conclusionsfemale sex ms type predictive worsening luts symptoms may less likely ascertained clinicians females compared males,0.0
critically appraised paper balance training cognitivebehavioural therapy promising reducing fatigue severity people multiple sclerosis commentary abstract,0.0
confirmatory factor analysis dutch screening visual complaints questionnaire people multiple sclerosis conclusions models may useful clinical care pwms onefactor model may give quick overview presence severity visual complaints general individual factors either three five factor models may contribute better recognition nature visual complaints pwms may guide steps rehabilitation pwms visual complaints,0.0
impact immunotherapies covid19 outcomes multiple sclerosis patients introduction sarscov2 pandemic led scientific community maximize efforts prevent infections disease severity patients multiple sclerosis pwms analyze impact immunotherapies covid19 outcomes pwms providing interpretation data,0.0
evolution acute black hole lesions patients relapsingremitting multiple sclerosis conclusions value lesiontocsf si ratio surface area found predictors black hole formation,0.0
potential application hydrogel diagnosis treatment multiple sclerosis multiple sclerosis ms chronic demyelinating disease central nervous system disorder may cause progressive permanent impairment placing significant physical psychological strain sufferers progress ms therapy marks significant advancement neurological research hydrogels can serve scaffold high water content high expansibility biocompatibility improve ms cell proliferation vitro therapeutic drug delivery cells vivo,1.0
impact covid19 pandemic physical therapy practice people multiple sclerosis multicenter survey study rims network abstractbackgroundthe impact covid19 pandemic physical therapy services people multiple sclerosis pwms unknown therefore special interest group mobility sig mobility european network best practice research multiple sclerosis rehabilitation rims undertaken initiative examine impact covid19 outbreak physical therapy services physical activity participation pwms across europe israel australiaobjectiveto describe impact covid19 outbreak physical therapy practice perspective therapistmethodsan online survey developed conducted december 2020 july 2021 survey 50 questions included multiplechoice questions openended responsesresultsin total 215 physical therapists pts 9 countries australia belgium czech republic ireland israel italy norway spain turkey participated study therapy affected pandemic aerobic training conditioning exercises 335 reported activities either reduced unavailable contrast 15 pts reported increased use relaxation mind body techniques fatigue management programs pandemic pts reported mixture positive negative feelings therapeutic sessions offered pandemic reported positive feelings included positive 265 optimistic 247 negative feelings frequently reported included worried 307 hesitant 209 pts reported 10 decrease use handson techniques 10 increase use oral instructions treating moderately severely pwms compared pandemicconclusionthe covid19 pandemic affected physical therapy services pwms internationally terms content frequency use format,0.0
parkinsonism multiple sclerosis patients prospective observational study abstractbackground rare cases coexisting multiple sclerosis parkinsonism reported literature however true prevalence clinical characteristics causal relation two entities systematically evaluatedobjective evaluate prevalence parkinsonism patients multiple sclerosis examine causal relationship anymethods consecutive patients referred multiple sclerosis clinic evaluated neurologist double training neuroimmunology movement disorders patients specifically screened movement disorders via movement disorder survey focused exam video samples independently rated two blinded movement disorder raters prespecified criteria developed five potential clinical scenarios incidental idiopathic parkinsons disease incidental parkinsonplus syndrome druginduced parkinsonism acute symptomatic parkinsonism chronic symptomatic parkinsonismresults 2016 2021 336 patients evaluated 12 patients 36 clinical parkinsonism average age 68 years 66 females nine patients 75 deemed incidental parkinsons disease 2 17 druginduced parkinsonism 1 83 deemed demyelinationrelated chronic symptomatic parkinsonism latter presented gradual progressive parkinsonism without prodromal symptoms blinded raters agreed parkinsonism phenomenology addition typical enhancing nonenhancing demyelinating lesions patient lesions bilaterally basal ganglia positive oligoclonal bands cerebrospinal fluid dat scan normal diagnosed ppms activity progression manifesting solely secondary parkinsonism disease stabilized ocrelizumab cases acute symptomatic parkinsonism coexisting parkinsonplus syndrome fiveyear duration study three incidental idiopathic parkinsons disease cases radiologically isolated syndromeconclusion parkinsonism ms rare cases incidental however clinicians need recognize entity demyelinationrelated chronic symptomatic parkinsonism patients progressive ms phenotypes demyelinating lesions basal ganglia upper midbrain parkinsonism may sole clinical presentation progressive ms indication dmt initiation escalation overrepresentation radiologically isolated syndrome patients presumptive incidental demyelination idiopathic parkinsons disease prospective studies utilizing highfield mri longitudinal dat scans needed better characterize complex relationship demyelination parkinsonism,1.0
prognosis walking function multiple sclerosis supported gait pattern analysis abstractbackground walking impairment common highly disabling symptom people ms pwms ambulatory deterioration poorly characterized pwms reliable prognosis may guide clinical decisions elusive study aimed objectively track progression clinical walking performance kinematic gait patterns pwms 4 years thereby revealing potential prognostic markers deterioration ambulatory functionmethods twentytwo pwms 488 99 years 14 females edss 45 09 points gait impairments recruited university hospital zurich switzerland gait function monitored period 4 years using set standardized clinical walking tests timed 25foot walk 6minute walk test 12item ms walking scale comprehensive 3d kinematic gait analysis walking decline assessed full patient cohort patient subgroups built according ms type relapsingremitting progressive subjects pathological gait signature cluster groups 13 results total cohort n22 found significant worsening 6mwt bl vs 4y 411m p00053 performance t25fw msws12 expanded disability status scale edss remained unchanged 4 years subjects pms n12 showed significant worsening edss bl vs 4y +06 points p00053 observed participants rrms n10 whereas deterioration clinical walking function different subjects rrms pms identified differences clinical walking deterioration pwms varying gait pattern pathologies subjects spasticparetic gait impairments cluster 1 n9 demonstrated marked worsening t25fw bl vs 4y +2 sec p00020 6mwt bl vs 4y 929m p 00001 seen pwms ataxialike cluster 2 n8 unstable walking pattern cluster 3 n5 deterioration clinical walking performance cluster 1 accompanied specific worsening gait deficits characteristic cluster baseline phenomenon found subgroups accordingly aggravation cluster 1specific gait impairments 4 years predicted deterioration 6mwt total cohort n22 accuracy 909 sensitivity 909 specificity 909 nagelkerkes coefficient determination r2 0721 unveiling key determinants msrelated walking declineconclusions findings highlight potential quantitative functional outcomes objective tracking disease progression pwms gait pattern analysis can provide valuable information underlying pathomechanisms gait deterioration may represent complementary prognostic tool walking function pwmsclinical trial clinicaltrialsgov nct01576354,1.0
parkinsonism multiple sclerosis patients prospective observational study abstractbackground rare cases coexisting multiple sclerosis parkinsonism reported literature however true prevalence clinical characteristics causal relation two entities systematically evaluatedobjective evaluate prevalence parkinsonism patients multiple sclerosis examine causal relationship anymethods consecutive patients referred multiple sclerosis clinic evaluated neurologist double training neuroimmunology movement disorders patients specifically screened movement disorders via movement disorder survey focused exam video samples independently rated two blinded movement disorder raters prespecified criteria developed five potential clinical scenarios incidental idiopathic parkinsons disease incidental parkinsonplus syndrome druginduced parkinsonism acute symptomatic parkinsonism chronic symptomatic parkinsonismresults 2016 2021 336 patients evaluated 12 patients 36 clinical parkinsonism average age 68 years 75 females nine patients 75 deemed incidental parkinsons disease 2 17 druginduced parkinsonism 1 83 deemed demyelinationrelated chronic symptomatic parkinsonism latter presented gradual progressive parkinsonism without prodromal symptoms blinded raters agreed parkinsonism phenomenology addition typical enhancing nonenhancing demyelinating lesions patient lesions bilaterally basal ganglia positive oligoclonal bands cerebrospinal fluid dat scan normal diagnosed ppms activity progression manifesting solely secondary parkinsonism disease stabilized ocrelizumab cases acute symptomatic parkinsonism coexisting parkinsonplus syndrome fiveyear duration study three incidental idiopathic parkinsons disease cases radiologically isolated syndromeconclusion parkinsonism ms rare cases incidental however clinicians need recognize entity demyelinationrelated chronic symptomatic parkinsonism patients progressive ms phenotypes demyelinating lesions basal ganglia upper midbrain parkinsonism may sole clinical presentation progressive ms indication dmt initiation escalation overrepresentation radiologically isolated syndrome patients presumptive incidental demyelination idiopathic parkinsons disease prospective studies utilizing highfield mri longitudinal dat scans needed better characterize complex relationship demyelination parkinsonism,1.0
effect virtual realitybased therapy fear falling multiple sclerosis systematic review metaanalysis abstractbackgroundvirtual realitybased therapies proposed rehabilitation people ms pwms systematic review aimed summarize effectiveness virtual realitybased vr therapy fear falling fof pwmsmethodspubmed via medline cochrane library cinahl scopus web science google scholar proquest databases systematically searched inception august 24 2021 randomized controlled trials rcts examining effect vr therapy fof pwms primary secondary outcome measure selected potential articles screened eligibility data extracted 3 independent reviewers methodological quality included studies assessed using pedro scale risk bias independently assessed three reviewers using cochrane collaboration risk bias tool raw unstandardized mean differences standard deviations differences included studies combined overall mean effect size calculated via fixedeffects model studyresultsfour rcts 140 participants included review metaanalysis studies included generally low unclear risk bias quality methodology low high metaanalysis confirmed vr therapy reduce fof pwms vr therapy promoted improvement greater conventional exercises balance exercises intervention md 298 95 ci 027 570 p00313 conclusionsthis study suggested vr therapy effective rehabilitative tool reducing fof pwms however due limited number studies included result interpreted caution,0.0
effect virtual realitybased therapy fear falling multiple sclerosis systematic review metaanalysis abstractbackgroundvirtual realitybased therapies proposed rehabilitation people ms pwms systematic review aimed summarize effectiveness virtual realitybased vr therapy fear falling fof pwmsmethodspubmed via medline cochrane library cinahl scopus web science google scholar proquest databases systematically searched inception august 24 2021 randomized controlled trials rcts examining effect vr therapy fof pwms primary secondary outcome measure selected potential articles screened eligibility data extracted 3 independent reviewers methodological quality included studies assessed using pedro scale risk bias independently assessed three reviewers using cochrane collaboration risk bias tool raw unstandardized mean differences standard deviations differences included studies combined overall mean effect size calculated via fixedeffects model studyresultsfour rcts 140 participants included review metaanalysis studies included generally low unclear risk bias quality methodology low high metaanalysis confirmed vr therapy reduce fof pwms vr therapy promoted improvement greater conventional exercises balance exercises intervention md 298 95 ci 027 570 p00313 conclusionsthis study suggested vr therapy effective rehabilitative tool reducing fof pwms however due limited number studies included result interpreted caution,0.0
effect dualtask training cognitive functions persons multiple sclerosis systematic review metaanalysis abstractbackgroundto summarize effectiveness cognitivemotor dualtask training dtt cognitive functions persons ms pwms methodsthe systematic search conducted pubmed web science physiotherapy evidence database scopus databases january 2022 methodological quality assessed using physiotherapy evidence database scale pooled effect sizes es 95 confidence interval ci calculated randomeffect modelsresultsa total 186 participants age ranges 35 567 six studies analyzed dtt improves executive function assessed frontal assessment battery es132 95 ci 076 187 p0001 nonsignificant beneficial effects cognitive processing speed sustained attention working memory evaluated using symbol digit modalities test es030 95 ci 006 066 p0102 paced auditory serial addition test es019 95 ci 033 071 p0474 also foundconclusionpwms may benefit cognitivemotor dtt improve cognitive functions benefit seems limited executive functions now larger sample randomized controlled trials needed,0.0
patientspecific outofpocket cost communication remote financial navigation patients multiple sclerosis randomized controlled feasibility study abstractobjectivewe conducted randomized controlled trial evaluating feasibility personalized outofpocket cost communication remote financial navigation counseling costcom intervention decreasing financial hardship among patients multiple sclerosis ms methodssixtytwo adult patients diagnosis ms prescription disease modifying therapy randomized 1 usual care n30 2 costcom n32 costcom included patientspecific outofpocket cost communication remote financial navigation counseling delivered enrollment 3 months usual care included routine neurology visits use available ancillary staff internal external resources financial assistance per normal clinic procedures feasibility outcomes included participation satisfaction costcom exploratory financial hardship outcomes included costrelated care nonadherence material hardship financial worry using comprehensive score financial toxicity cost resultsmean age 415 810 female 414 white 517 black race 32 costcom patients 968 687 completed baseline followup intervention financial assistance application completed 80 mean general satisfaction 5 costcom 3110 multivariable analyses costcom patients less financial worry ie higher cost scores 3 months compared usual care patients b coefficient 36 95 ci 01 71 costcom patients significant decreases 3 months nonadherence 727 compared enrollment 50 3 months nonadherence material hardship significantly different two armsconclusioncostcom interventions feasible acceptable yield potential benefits decreasing financial hardshiptrial registration study registered clinicaltrialsgov nct04257071,0.0
hypogammaglobulinemia infections covid19 people multiple sclerosis treated ocrelizumab abstractobjectiveto determine influence immunoglobulins ig level rate infections people multiple sclerosis pwms treated ocrelizumabmethodswe enrolled 109 consecutive pwms treated ocrelizumab mean followup 269056 136427 years retrospectively searched electronic database following information collected age sex ms characteristics number ocrelizumab cycles infections duration infection hospitalization due infection treatment infection covid19 characteristics ig levels measured within 14 days ocrelizumab infusionresultsnumber pwms values igm igg lower level normal baseline 3 28 2 28 respectively 6th cycle ocrelizumab 5 135 5 135 respectively levels igm steadily decreasing time levels igg started show statistically significant drop 5th cycle ocrelizumab 587 pwms experienced infection treatment median number infections per pwms 1 range 04 female sex increased risk infection hr 2561 95ci 13824774 p0003 higher age smaller drop igm 3rd ocrelizumab cycle increased risk infection requiring hospitalization hr 1086 95ci 10181159 p0013 hr 9216 95ci112475558 p0039 respectively longer disease duration increased risk covid19 hr 1075 95ci 10021154 p0045 conclusionthe present findings broaden limited realworld data infection covid19 risk pwms treated ocrelizumab,0.0
intranasal delivery smallmolecule erbb inhibitor promotes recovery acute latestage cns inflammation multiple sclerosis ms autoimmune inflammatory disease cns characterized demyelination axonal degeneration although several established treatments reduce relapse burden effective treatments halt chronic progression scarce singlecell transcriptomic studies ms animal models described astrocytes spatial functional heterogeneity important cellular determinants chronic disease combined cns singlecell transcriptome data,1.0
time course lesioninduced atrophy multiple sclerosis conclusion increased rates thalamic dgm atrophy restricted 1 year following newly developed disruption connected wm tracts research clinical settings additional gray matter atrophy may expected 1 year following new lesion growth connected white matter,0.0
oral cladribine patients change firstline disease modifying treatments multiple sclerosis protocol prospective effectiveness safety study clad cross conclusions clad cross will provide efficacy data cladribine tablets used followup treatment firstline dmds realworld setting will establish safety profile will collect information support pharmacoeconomic studies,0.0
analysis plasma using flow cytometry reveals increased immune cellderived extracellular vesicles untreated relapsingremitting multiple sclerosis extracellular vesicles evs secreted cells physiological pathological conditions found biological fluids displaying specific surface markers indicative cell origin evs emerged important signaling entities may serve putative biomarkers various neurological conditions including multiple sclerosis ms objective study measure compare immune cellderived evs within human plasma untreated,0.0
role autophagy function cd4sup+ sup t cells development chronic inflammatory diseases uncontrolled acute inflammation progresses persistent inflammation leads various chronic inflammatory diseases including asthma crohns disease rheumatoid arthritis multiple sclerosis systemic lupus erythematosus cd4 + t cells key immune cells determine development chronic inflammatory diseases cd4 + t cells orchestrate adaptive immune responses producing cytokines effector molecules functional roles t cells vary depending,0.0
effects vitamin d body mass index disease risk relapse hazard multiple sclerosis mendelian randomization study background objectives decreased vitamin d levels obesity associated increased risk multiple sclerosis ms however whether also affect disease course onset remains unclear larger data sets now available used mendelian randomization mr determine whether serum 25hydroxyvitamin d 25ohd body mass index bmi causally associated ms risk moving beyond susceptibility toward heterogeneity relapse hazard,0.0
intermediate uveitis etiologies outcomes tertiary referral hospital ksa conclusion study demonstrated kkesh iu cases idiopathic associated ms tuberculosis visual prognosis favorable even long duration iu numerous complications,0.0
new perspectives developing therapeutic bioconjugates metabolitedepleting enzymes lessons learned combating glutamate excitotoxicity glutamate main excitatory neurotransmitter central nervous system plays essential role several cognitive activities memorizing learning excessive glutamate release disturbance glutamate homeostasis participates multiple neuronal pathologies including cerebral ischemia inadequate blood supply traumatic brain injury eg fall accident multiple sclerosis epilepsy migraine fetal hypoxia alzheimers disease attenuating,0.0
effects cigarette smoke exposure mouse model multiple sclerosis multiple sclerosis ms inflammatory autoimmune disease associated genetic environmental factors cigarette smoking harmful health may one risk factors ms however systematic investigations controlled experimental conditions linking cigarette smoke cs ms present study first inhalation study correlate preclinical pathological manifestations affected different doses cs exposure mouse,0.0
oxidized phospholipids novel mediators neurodegeneration neurodegeneration drives progression many neurological diseases inflammation oxidative stress occurring cns promote lipid peroxidation leading generation oxidized phospholipids oxidized phosphatidylcholines oxpcs oxpcs proposed biomarkers oxidative stress detection lesions multiple sclerosis ms frontotemporal lobe dementia spinal cord injury amyotrophic lateral sclerosis als implies oxidative insult,0.0
lack association b 12 body mass index among saudi multiple sclerosis patients conclusion findings revealed association serum vitamin b12 concentration tsh bmi ms clinical parameters however studies required validate results,0.0
quantitative effect sex disease activity disability accumulation multiple sclerosis conclusion women inflammatory disease activity terms relapses men age menopause indicating sex hormones may play role men subject neurodegenerative component ms women particularly age 45 years,0.0
primary progressive multiple sclerosis overlapping antigad antihu antibodies positive neurological syndromes clinical considerations abstract,0.0
recommendations use propensity score methods multiple sclerosis research conclusion comprehensive set recommendations highlights key elements require careful attention using propensity score methods,0.0
vaccination immunotherapies neuroimmunological diseases neuroimmunological diseases treatment compromise immune system thereby increasing risk infections serious illness consequently vaccinations protect infections important part clinical management diseases however wide variety immunotherapies currently used treat neuroimmunological disease particularly multiple sclerosis neuromyelitis optica spectrum disorders can also impair immunological responses,0.0
preferencebased multiple sclerosis index assessment psychometric properties translation turkish conclusion turkish version pbmsi good psychometric properties assess healthrelated quality life people multiple sclerosis pbmsisg preferred pbmsirsimplications rehabilitationhealthrelated quality life often used primary secondary endpoint multiple sclerosis researchthe preferencebased multiple sclerosis index first preferencebased healthrelated quality life measure developed multiple sclerosis using patient,0.0
subcutaneous calcinosis different systemic sclerosis dermatomyositis calcinosis cutis deposition insoluble calcium skin subcutaneous tissues manifestation several autoimmune connective tissue diseases frequently systemic sclerosis juvenile dermatomyositis followed adult dermatomyositis autoimmune connective tissue diseaseassociated calcinosis dystrophic subtype occurs sites damaged tissue setting normal serum calcium phosphate levels juvenile dermatomyositis calcinosis,0.0
varicellazoster reactivation nonimmunized elderly multiple sclerosis patient delayedrelease dimethyl fumarate grade 2 lymphopenia profoundly low cd4+ cd8+ cell counts case report increased susceptibility opportunistic infections oi multiple sclerosis ms patients real concern amongst neurologists using diseasemodifying therapies dmts dmts used modulating suppressing immune system ms management may risk patient lymphocytopenia raising possibility oi however lymphopenia may contemplate biomarker drug response degree immunomodulation drug compliance oi reactivation,0.0
body mass index interleukin6 signaling multiple sclerosis mendelian randomization study conclusion study identified il6 signaling major mediator association bmi risk ms explorations pathways underlying association bmi ms required will together findings improve understanding ms biology potentially lead improved opportunities targeted prevention strategies,0.0
paul klees gastrointestinal maladies series historical clinical vignettes part iv paul klee 18791940 20 th century swissgerman artist suffered died complications systemic sclerosis ssc scleroderma series clinical historical vignettes various symptoms complications klees scleroderma described present evidence klees multiple gastrointestinal gi symptoms significant impact quality life,0.0
pathogenesis amyotrophic lateral sclerosis mitochondrial dysfunction protein misfolding epigenetics amyotrophic lateral sclerosis als neurodegenerative disease multiple complex mechanisms involved among mitochondrial dysfunction plays important role als multiple studies shown mitochondria closely associated reactive oxygen species production oxidative stress exhibit different functional states different genetic backgrounds review explored roles ca 2+ autophagy mitochondrial quality control regulation,0.0
baseline inflammatory status reveals dichotomic immune mechanisms involved primaryprogressive multiple sclerosis pathology conclusion baseline inflammation influences immunological pathways predominate patients ppms inflammatory b cells played pivotal role gd+ group inflammatory t innate immune cells gd patients b cell depletion can modulate mechanisms,0.0
immunological changes following electroconvulsive therapy multiple sclerosis conclusion patient trd ms ect safe feasible see neurobiological signs disease activation ms neurodegeneration course ect may even beneficial led increase neuroprotective ccl2 pathway presented patient,1.0
immune genes outside immune cells multiple sclerosis issue neuron meijer agirre et al 2022 demonstrate immune genes exhibit primed chromatin state healthy oligodendroglia transcriptionally activated ms series epigenetic activations including histone modification deposition transcription factor binding chromatin reconfiguration,0.0
migraine interferon 1a siponimod immunomodulator therapies conclusions interferon 1a might efficic therapy autoimmune migraine numerous immunomodulators currently available systemic autoimmune diseases associated comorbid migraine examining effect immunomodulatory therapies comorbid migraine headache beneficial finding specific immunomodulator therapy autoimmune migraine,0.0
role transcranial magnetic stimulation surrogate marker disease activity patients multiple sclerosis literature review conclusion discovery specific detailed neurophysiological parameters surrogate endpoints disease activity represent important step clinical trials changes cortical connectivity already demonstrated ms clinical practice measures typically used evaluate disease activity speculate tms might effective identifying disease progression leads longterm disability compared standard surrogate markers,0.0
identification hostpathogendisease relationships using scalable multiplex serology platform uk biobank certain infectious agents recognised causes cancer chronic diseases understand pathological mechanisms underlying relationships design multiplex serology platform measure quantitative antibody responses 45 antigens 20 infectious agents including human herpes hepatitis polyoma papilloma retroviruses well chlamydia trachomatis helicobacter pylori toxoplasma gondii assayed random subset 9695 uk biobank,0.0
transcription factor cmaf promotes immunoregulation programmed cell death 1expressed cd8 + t cells multiple sclerosis background objectives multiple sclerosis ms inflammatory demyelinating disease cns cd8 + t cells prominently found inflammatory sites recent advances understanding checkpoint molecules including programmed cell death 1 pd1 expressed cd8 + t cells highlight immune regulatory roles tcell subset however role cd8 + t cells ms unclear thus aimed reveal characteristics pd1expressed pd1 + cd8 + t cells,1.0
covid19 vaccines patients multiple sclerosis willingness unwillingness hesitancy systematic review metaanalysis conclusion according findings systematic review metaanalysis twothirds patients ms willing obtain covid19 vaccines,0.0
critically appraised paper balance training cognitivebehavioural therapy promising reducing fatigue severity people multiple sclerosis synopsis abstract,0.0
csf strem2 neurological diseases twosample mendelian randomization study conclusions findings provide support potential causal relationship elevated csf strem2 levels higher risk multiple sclerosis,0.0
effect rapamycin mogreactive immune cells lipopolysaccharideactivated microglia vitro approach screening new therapies multiple sclerosis rapamycin immunomodulatory drug evaluated preclinical clinical trials diseasemodifying therapy multiple sclerosis ms study evaluated vitro effect rapamycin immune cells pivotally involved pathogenesis experimental autoimmune encephalomyelitis eae animal model study ms splenocytes central nervous system cns mononuclear cells obtained eae mice stimulated myelin oligodendrocyte,1.0
clinical radiological effectiveness natalizumab extended dosage interval patients relapsing multiple sclerosis conclusions edi ntz maintains high clinical activity effectiveness mri,0.0
independent temporal lobe epilepsy patients tuberous sclerosis complex tuberous sclerosis complex tsc rare disease involves multiple organs including brain approximately 8090 tsc patients exhibit tscassociated epilepsy independent temporal lobe epilepsy tle tscunrelated epilepsy particularly rare patients tsc describe three patients tsc independent tles confirmed stereoelectroencephalography eeg postoperative pathological findings seizure outcome followup patients,0.0
multisite mri reproducibility lateral ventricular volume using naims cooperative pilot dataset conclusion fully automated lvv segmentation higher absolute variability wbv much lower relative variability compared clinically relevant changes may therefore meaningful proxy outcome measure neurodegeneration,0.0
progressive buildup perineuronal nets somatosensory cortex associated development chronic pain mice chronic pain sustained maladaptive form neuronal plasticity occurring stations pain neuraxis including cortical regions pain matrix report chronic inflammatory pain induced unilateral injection complete freund9s adjuvant cfa hindpaw male mice associated progressive buildup perineuronal nets pnns contralateral somatosensory cortex ssc medial prefrontal cortex mpfc reticular thalamic nucleus ssc density pnns labeled wisteria floribunda agglutinin wfa increased 3 7 d following cfa injection 7 d mpfc number parvalbumin pv positive interneurons enwrapped wfa+ pnns also increased three brain regions mice injected cfa remarkably pnn degradation induced intracortical infusion chondroitinaseabc significantly reduced mechanical thermal pain also reversed increased frequency ipscs recorded layer 5 pyramidal neurons contralateral ssc cfainjected mice findings suggest possible relationship cortical pnns nociceptive sensitization support hypothesis pnns maintain plasticity adult life regulate cortical responses sensory inputssignificance statement brain extracellular matrix provides structural support also regulates synapse formation function modulates neuronal excitability found chronic inflammatory pain mice enhances density perineuronal nets pnns somatosensory cortex medial prefrontal cortex remarkably enzymatic degradation pnns somatosensory cortex caused analgesia reversed alterations inhibitory synaptic transmission associated chronic pain findings disclose novel mechanism nociceptive sensitization support role pnns mechanisms neuronal plasticity adult brain,0.0
monoclonal antibodies treatment relapsing multiple sclerosis overview emphasis pregnancy vaccination risk management monoclonal antibodies become mainstay treatment patients relapsing multiple sclerosis rms provide benefit patients primary progressive ms highly precise specifically targeting molecules displayed cells involved distinct immune mechanisms ms pathophysiology differ target antigen recognize also mode action generates therapeutic effect natalizumab formula see text 4 formula,0.0
therapeutic potential clinical evidence hesperidin neuroprotective agent conclusion present study highlights benecial neuropharmacological potential hesperidin including anticonvulsant antidepressant antioxidant antiinammatory memory locomotor enhancing activities,1.0
rortexpressing pathogenic cd4sup+ sup t cells cause brain inflammation chronic colitis neurobehavioral disorders brain abnormalities extensively reported crohns disease ulcerative colitis patients however mechanism causing neuropathological disorders inflammatory bowel disease patients remains unknown studies linked th17 subset cd4 + t cells brain diseases associated neuroinflammation cognitive impairment including multiple sclerosis ischemic brain injury alzheimers disease better understand cd4 + t,0.0
patterns white gray structural abnormality associated paediatric demyelinating disorders impact multiple sclerosis ms myelin oligodendrocyte glycoprotein mog associated disorders mogad brain structure youth remains poorly understood reductions cortical mantle thickness structural mri abnormal diffusionbased white matter metrics eg diffusion tensor parameters well documented ms mogad characterizing structural abnormalities found children disorders can help clarify differences similarities,1.0
direction magnitude displacement differ slowly expanding nonexpanding multiple sclerosis lesions compared small vessel disease conclusion lesion dynamics may reveal distinct characteristics associated biology disease providing insights behavior inflammatory cns disorders,0.0
astroglial oligodendroglial markers cuprizone animal model de remyelination myelin loss consecutive axon degeneration impaired remyelination underlying causes progressive disease patients multiple sclerosis astrocytes suggested play major role processes unmasking distinct astrocyte identities health disease help understand pathophysiological mechanisms astrocytes involved however number specific astrocyte markers limited therefore performed immunohistochemical,1.0
relationship fatigue clinically accessible measure switching individuals multiple sclerosis conclusions may unique relationship fatigue switching processes identifiable clinical measures switching future research continue investigate relationship using behavioral neural markers test models fatigue eventually identify specific intervention targets,0.0
imaging multiple sclerosis abstract,0.0
longterm efficacy safety siponimod patients secondary progressive multiple sclerosis analysis expand core extension data gt 5 years conclusion sustained efficacy consistent longterm safety profile siponimod 5 years support clinical utility longterm treatment spms benefits continuous siponimod versus placebosiponimod group highlight significance earlier treatment initiation,0.0
association adverse childhood experiences development multiple sclerosis objective study whether exposure childhood emotional sexual physical abuse associated subsequent multiple sclerosis ms development,0.0
blood neurofilament light progressive multiple sclerosis post hoc analysis 2 randomized controlled trials conclusion pnfl associated future clinical radiological disability progression features group level pnfl reduced treatment may meaningful outcome measure pms studies,0.0
changes thumb tapping rates central motor conduction times associated persons multiple sclerosis introduction persons multiple sclerosis nerve conductivity can reduced assessment generally performed via motor evoked potentials mep far strongly associated motor performance surrogate changes extracted central motor conduction time cmct missing,0.0
pregnancy outcomes women multiple sclerosis treated ocrelizumab canada descriptive analysis realworld data abstractobjectives report describe realworld use ocrelizumab women multiple sclerosis ms canada pregnancy well fetal outcomesmethodswe identified retrospective prospective canadian pregnancy exposure cases roche global safety database november 5 2008 march 31 2021 linked cases information within canadian roche patient support program compass analysis included spontaneous reports noninterventional program details pregnancy exposures fetal outcomes well relevant patient characteristics collectedresults total 107 cases maternal exposures retrieved 104 972 prescribed ocrelizumab relapsingremitting ms rrms 105 981 reported compass program cases 85 794 prospective 22 206 retrospective cases pooled n65 unknown lost followup outcomes ongoing pregnancies excluded cases reporting outcome analyzed including 47 723 live births 447 full term 85 preterm 468 unknown gestational age 13 200 spontaneous abortions 2 31 therapeutic abortions elective terminations 3 46 ectopic pregnancies one major congenital anomaly limb polydactyly reported however multiple confounders likely contributors total maternal exposures n107 50 cases 466 exposed ocrelizumab utero 32 640 receiving last ocrelizumab infusion 3 6 months prior conception 17 340 receiving 6 months prior conception 1 case receiving unknown time point utero among 37 346 maternal exposure cases exposed utero 22 595 received last ocrelizumab infusion 3 months prior conceptionconclusion data presented although without limitations continues suggest increased risk congenital anomalies consistent ocrelizumab global pregnancy safety data epidemiological rates,0.0
pregnancy outcomes women multiple sclerosis treated ocrelizumab canada descriptive analysis realworld data abstractobjectivesto report describe realworld use ocrelizumab women multiple sclerosis ms canada pregnancy well fetal outcomesmethodswe identified retrospective prospective canadian pregnancy exposure cases roche global safety database november 5 2008 march 31 2021 linked cases information within canadian roche patient support program compass analysis included spontaneous reports noninterventional program details pregnancy exposures fetal outcomes well relevant patient characteristics collectedresultsa total 107 cases maternal exposures retrieved 104 972 prescribed ocrelizumab relapsingremitting ms rrms 105 981 reported compass program cases 85 794 prospective 22 206 retrospective cases pooled n65 unknown lost followup outcomes ongoing pregnancies excluded cases reporting outcome analyzed including 47 723 live births 447 full term 85 preterm 468 unknown gestational age 13 200 spontaneous abortions 2 31 therapeutic abortions elective terminations 3 46 ectopic pregnancies one major congenital anomaly limb polydactyly reported however multiple confounders likely contributors total maternal exposures n107 50 cases 466 exposed ocrelizumab utero 32 640 receiving last ocrelizumab infusion 3 6 months prior conception 17 340 receiving 6 months prior conception 1 case receiving unknown time point utero among 37 346 maternal exposure cases exposed utero 22 595 received last ocrelizumab infusion 3 months prior conceptionconclusionthe data presented although without limitations continues suggest increased risk congenital anomalies consistent ocrelizumab global pregnancy safety data epidemiological rates,0.0
evidencebased management multiple sclerosis spasticity nabiximols oromucosal spray clinical practice 10year recap effective symptomatic management multiple sclerosis ms spasticity remains unmet need many patients secondline option nabiximols widely investigated noninvasive antispasticity medications patient population clinical evidence accumulated nabiximols since first approved europe 2010 suggests 40 initial responders ie 20 improvement baseline 010 numerical rating scale score may expect achieve,1.0
sexual dysfunction women multiple sclerosis expectations regarding treatment information utility seamsf questionnaire conclusion date seamsf questionnaire validated women ms evaluation sexual expectations present study women felt strongly represented useful way introduce discuss subject sexual dysfunction doctor audrey sb marion r batrice m et al sexual dysfunction women multiple sclerosis expectations regarding treatment information utility seamsf questionnaire sex,0.0
proposals french expert panel respiratory care als patients conclusion french expert panel proposes evidencebased review update respiratory care recommendations als patients daily practice,0.0
clinically deployed computational assessment multiple sclerosis lesions multiple sclerosis ms demyelinating disease central nervous system affects nearly 1 million adults united states magnetic resonance imaging mri plays vital role diagnosis treatment monitoring ms patients particular followup mri t2flair images brain depicting white matter lesions mainstay monitoring disease activity making treatment decisions article present computational approach deployed,1.0
association maintenance intravenous immunoglobulin prevention relapse adult myelin oligodendrocyte glycoprotein antibodyassociated disease conclusions relevance results retrospective multicenter cohort study adult patients mogad suggest maintenance ivig associated reduction disease relapse less frequent lower dosing ivig may associated treatment failure future prospective randomized clinical trials warranted confirm findings,1.0
effects dimethyl fumarate brain atrophy relapsingremitting multiple sclerosis pooled analysis phase 3 define confirm studies conclusions lower rate whole brain volume loss dmf pooled bpf analysis second year vs pbo consistent effects relapses disability mri lesions brain volume changes first year may explained pseudoatrophy effects also described ms clinical trials,0.0
tenascins interfere remyelination ex vivo cerebellar explant model demyelination oligodendrocytes form myelin membranes thereby secure insulation axons rapid conduction action potentials diseases multiple sclerosis highlight importance glial cell population brain function adult brain efficient remyelination following damage oligodendrocytes compromised myelination characterized proliferation migration proper integration oligodendrocyte precursor cells opcs processes among others,1.0
genetic variants embaff em gene risk fatigue among patients primary sjgrens syndrome conclusions report novel association genetic makeup primary ssassociated fatigue rs9514828 tt genotype decreasing likelihood fatigue development among patients findings need validation multicenter studies,0.0
evaluation psychometric properties jebsen taylor hand function test jthft italian individuals multiple sclerosis introduction jebsen taylor hand function test jthft nondiagnostic assessment scale hand upper limb dexterity commonly used various countries around world diseases muscular dystrophy stroke spinal cord injury parkinson carpal tunnel syndrome rheumatoid arthritis study aimed evaluate psychometric properties jthft italian adults multiple sclerosis ms,0.0
aging multiple sclerosis agerelated factors socioeconomic risks conclusion danish patients ms higher risk losing income earnings much higher risk receiving disability pension compared healthy controls,0.0
multiple sclerosis risk cardiovascular diseases mendelian randomization study conclusions provided suggestive genetic evidence causal associations ms increased risk cad mi hf ais highlighted significance active monitoring prevention cardiovascular risk combat cardiovascular comorbidities ms patients,0.0
better cognitive function predicts maintenance dualtask walking ability time among people relapsingremitting ms conclusions results provide longitudinal evidence better cognitive function specifically global moca score may protect decline dualtask walking ability years psycinfo database record c 2022 apa rights reserved,0.0
cooccurrence hereditary angioedema multiple sclerosis therapeutic management diseases fingolimod conclusions herein provide long term evaluation extremely rare case concomitant existence hae ms present effects ms current diseasemodifying therapies hae attacks case highlights possible effect fingolimod immunoregulatorymechanisms implicated diseases,0.0
mrnacovid19 vaccination can considered safe tolerable frail patients conclusions study reports mrnacovid19 vaccination safe also frail patients expected side effects manageable minimum impact patient care path,0.0
misdiagnosis hiv toxoplasmosis encephalopathy progressive memory loss initial symptom case report toxoplasmosis encephalopathy te kind encephalopathy parasitic disease caused toxoplasma gondii common opportunistic central system infection patients acquired immunodeficiency syndrome aids human immunodeficiency virus without early diagnosis proper treatment opportunistic infection can lifethreatening common clinical manifestations disease include altered mental state epilepsy cranial nerve damage paresthesia,0.0
clemastine induces impairment developmental myelination abnormalities myelination associated behavioral cognitive dysfunction neurodevelopmental psychiatric disorders thus therapies promote accelerate myelination potentially ameliorate symptoms autism clemastine histamine h1 antagonist anticholinergic properties muscarinic m1 receptor promising drug promyelinating properties clemastine penetrates blood brain barrier efficiently promotes remyelination different animal,1.0
alemtuzumabinduced autoimmune thyroid dysfunction alemtuzumab humanized monoclonal antibody used diseasemodifying treatment relapsingremitting multiple sclerosis rrms frequently causes autoimmunity principal adverse effect describe typical case young man treated two courses alemtuzumab presenting 18 months later initial hyperthyroidism due graves disease gd followed persistent hypothyroidism discuss pathophysiological role stimulating blocking thyrotropin receptor antibodies,0.0
comparing longterm clinical economic impact ofatumumab versus dimethyl fumarate glatiramer acetate patients relapsing multiple sclerosis costconsequence analysis societal perspective germany conclusion immediate omb treatment early switch improves clinical productivity outcomes remaining almost cost neutral compared late switches,0.0
efficacy safety mesenchymal stem cell transplantation treatment autoimmune diseases rheumatoid arthritis systemic lupus erythematosus inflammatory bowel disease multiple sclerosis ankylosing spondylitis systematic review metaanalysis randomized controlled trial conclusion mscs certain effect different autoimmune diseases rcts needed modify confirm conclusion,0.0
prolongedrelease fampridine treatment myoclonus cervical myelitis case report prolongedrelease fampridine prfam potassium channel blocker approved improving walking ability patients multiple sclerosis ms beyond positive effects ms symptoms like fatigue cognition tremor described knowledge positive effect prfam spinal myoclonus described far report 32yearold female myoclonus cervical myelitis affecting hands markedly improved administration,0.0
aberrant cerebral iron trafficking comorbid chronic inflammation molecular mechanisms pharmacologic intervention redox properties make iron essential nutrient also make iron efficient prooxidant given nascent cytotoxicity iron homeostasis relies combination iron transporters chaperones redox buffers manage nonphysiologic aqueous chemistry firstrow transition metal although mechanistic understanding link brain iron accumulation bia neurodegenerative diseases lacking bia comorbid majority cognitive motor,0.0
multiple sclerosis severity score msss improves accuracy individualized prediction ms conclusion addition single readily available metric msss comprehensive msbase prediction model considerably improved individual accuracy prognostics ms,0.0
correction management hepatitis b virus prophylaxis patients treated diseasemodifying therapies multiple sclerosis multicentric italian retrospective study abstract,0.0
investigating demyelination efficient remyelination remyelination failure organotypic cerebellar slice cultures workflow practical tips healthy myelin essential proper brain function myelin sheath damaged fast saltatory impulse conduction lost neuronal axons become vulnerable degeneration thus regeneration myelin sheath encouraging oligodendrocyte lineage cells remyelinate denuded axons promising therapeutic target demyelinating diseases multiple sclerosis ex vivo organotypic cerebellar slice cultures useful model study developmental myelination,1.0
magnetization transfer ratio assessing remyelination transcranial ultrasound stimulation lysolecithin rat model multiple sclerosis shown transcranial ultrasound stimulation tus capable attenuating myelin loss providing neuroprotection animal models brain disorders study investigated ability tus promote remyelination lysolecithin lpc induced local demyelination hippocampus demyelination induced microinjection 15 l lpc 1 rat hippocampus treated group received daily tus 5 12 days magnetic resonance imaging,1.0
preclinical model multiple sclerosis focal chemical viral demyelination multiple sclerosis ms characterized presence demyelinating lesions central nervous system cns demyelination accompanied axonal degeneration activation cells innate adaptive immune systems accumulate around demyelinated plaques oligodendrocyte cell dysfunction death also evident relapsingremitting form ms dysfunction followed periods recovery newly mature oligodendrocytes ability,1.0
distinct mechanisms underlying therapeutic potentials cd20 neurological neuromuscular disease cluster differentiation 20 cd20 integral membrane protein expressed mainly different developmental stages b lymphocytes rarely t lymphocytes functions link b cell antigen receptor bcr immune microenvironment via regulating calcium ion influx cell cycle progression interaction isotypic bcrs coreceptors diverse therapeutic monoclonal antibodies mabs targeting cd20 generated grouped two types based ability,1.0
extension evaluation promis sexual function satisfaction measures use adults living multiple sclerosis conclusion study extended promis sexfs brief full profiles create sexfsms adding items measure relevant issues related sexual function individuals living ms amtmann d bamer salem r et al extension evaluation promis sexual function satisfaction measures use adults living multiple sclerosis j sex med 2021 xxxxxxxx,0.0
preclinical model multiple sclerosis methods autoimmune demyelination multiple sclerosis ms chronic demyelinating disease central nervous system cns characterized progressive demyelination neurodegeneration considered autoimmune disorder autologous myelinreactive t cells infiltrate cns activate peripheral resident innate immune cells promote local inflammation ms humans characterized wide variety clinical disease courses made disease complex model experimental,1.0
quantitative assessment myelin density using 11 c medas pet patients multiple sclerosis firstinhuman study conclusion 11 c medas pet can used quantification myelin density ms patients able distinguish differences myelin density within ms lesions 2t3k model optimal compartment model mlair2 best simplified method quantification,1.0
tcell surveillance human brain health multiple sclerosis circulating tissueresident t cells collaborate protection tissues harmful infections malignant transformation also can instigate autoimmune reactions similar roles t cells brain less evident due compartmentized organization central nervous system cns recent years beneficial well occasional detrimental effects tcelltargeting drugs people early multiple sclerosis ms increased interest t cells,0.0
barriers gaps headache education national crosssectional survey neurology residents denmark conclusions overall knowledge headache disorders amongst neurology residents denmark meet expectations set national international recommendations stakeholders make strategic initiatives structured education headache improved clinical outcomes parallel costs reduction resource optimization,0.0
physical activity vascular comorbidity black white persons multiple sclerosis crosssectional study conclusions findings indicate mvpa higher white black persons ms mvpa associated lower vascular comorbidity white persons ms physical activity behavior might potential target managing vascular comorbidity white persons ms,0.0
inhibition ripk1 zju37 promotes oligodendrocyte progenitor proliferation remyelination via nfb pathway receptor interacting serine threonine protein kinase 1 ripk1 activation necroptosis genetically mechanistically linked human multiple sclerosis neurodegenerative diseases demyelination common key pathology demyelination can healed remyelination mediated new oligodendrocytes derived adult oligodendrocyte progenitor cells opcs unfortunately efficiency remyelination declines progressive aging partially due,1.0
hidebound bowel sign systemic sclerosis systemic sclerosis ssc characterized excess collagen deposition multiple organs resulting dilatation intestine delayed transit chronic intestinal pseudoobstruction cipo bacterial overgrowth 58yearold woman 2year history ssc presented alternating diarrhea constipation,0.0
environmental risk factors multiple sclerosis bridging mendelian randomization observational studies multiple sclerosis ms complex disease genetic variants environmental factors involved disease susceptibility main environmental risk factors associated ms observational studies include obesity vitamin d deficiency epsteinbarr virus infection smoking modifying environmental lifestyle factors may enable prevention important pinpoint causal links factors ms leveraging genetics mendelian randomization,0.0
inhibition colony stimulating factor1 receptor csf1r potential therapeutic strategy neurodegenerative diseases opportunities challenges microglia specialized dynamic immune cells central nervous system cns plays crucial role brain homeostasis disease states persistent neuroinflammation considered hallmark many neurodegenerative diseases including alzheimers disease ad parkinsons disease pd huntingtons disease hd amyotrophic lateral sclerosis als primary progressive multiple sclerosis ms colony stimulating factor 1receptor csf1r predominantly expressed,0.0
neuroprotective effect liraglutide experimental mouse model multiple sclerosis role ampk sirt1 signaling nlrp3 inflammasome heterogeneous nature multiple sclerosis ms unavailability treatments addressing intricate network reversing disease state yet area needs elucidated liraglutide glucagonlike peptide1 analogue recently exhibited intriguing potential neuroprotective effects currents study investigated potential effect mouse model ms possible underlying mechanisms demyelination induced c57bl 6 mice cuprizone 400 mg kg day,1.0
stable multiple sclerosis patients anticd20 therapy go extended interval dosingcommentary abstract,0.0
proposal post hoc quality control instrumented motion analysis using markerless motion capture development usability study conclusions present qc pipeline seems feasible useful instant quality screening clinical setting results confirm need qc despite using standard test setups testing protocols operator training employed system extension taskbased motor assessment technologies results qc process can used clean existing data sets optimize quality assurance measures well foster development automated qc approaches,0.0
epsteinbarr virus driver multiple sclerosis accumulating evidence implicates epsteinbarr virus ebv etiological factor multiple sclerosis ms ebv driver causes antiviral immunity associated autoimmune components rather trigger unleashes selfperpetuating autoimmunity elimination ebv rational therapy ms,0.0
multiple sclerosis diagnosis diseasemodifying therapy prognosis background multiple sclerosis ms multifocal inflammatory central nervous system disorder now many highly effective diseasemodifying therapies dmts available treatment options significant impact disease activity longterm disabilityobjective aim article provide concise overview diagnosis dmts prognosis msdiscussion diagnosis ms made clinicoradiological grounds prove dissemination disease time space nervous system expanding options dmts significant impact disability make medication selection individual patients complicated patients ms often model care shared neurologist general practitioner review article summarises key aspects diagnosis dmts prognosis ms relevant general practitioner,0.0
human serum albumin neurodegeneration serum albumin sa exists relatively high concentrations close contact cells however adult brain except cerebrospinal fluid csf sa concentration relatively low mainly produced liver serve main protein blood plasma plasma functions carrier chaperon antioxidant source amino acids osmoregulator etc carrier facilitates stable presence transport hydrophobic hydrophilic molecules,0.0
cognitive rehabilitation multiple sclerosis background although cognitive impairment common disabling multiple sclerosis ms approved pharmacological treatments fortunately now good evidence cognitive rehabilitation effective ms however healthcare providers unaware treatment options,0.0
application diffusion kurtosis imaging heterogeneous white matter relapsingremitting multiple sclerosis conclusion applying dki imagingbased white matter classification potential reflect white matter damage correlated cognitive impairment,0.0
cognitive impairment multiple sclerosis role general practitioner cognitive screening care coordination background cognitive impairment common multiple sclerosis ms can impact aspects daily life also early marker increased ms disease activity indicates need optimise diseasemodifying therapies slow progression preserve brain functioning however difficult detect clinical interview alone patient selfreport unreliable,0.0
patient selfmanagement empowerment multiple sclerosis implications dietary lifestyle management primary care background multiple sclerosis ms chronic neurological condition increasing prevalence many people living ms will trial various alternative therapies including changed patterns eating try gain control condition new clinical guidelines advise reducing time first clinical symptoms treatment support healthcare team can empower person healthcare journey,0.0
secondary prevention radiologically isolated syndromes prodromal stages multiple sclerosis following extraordinary progress treatment multiple sclerosis ms two major unmet needs remain understanding etiology disease hence designing definitive cures perspective neither hand can taken granted etiologic targets will readily treatable prevention overt disabling disease seems realistic pragmatic perspective integration genetic data endophenotypes mri,0.0
walking impairment patients multiple sclerosis impact complex motor nonmotor symptoms across disability spectrum background multiple sclerosis ms neurodegenerative pathology affects young people prime lives often impact motor tasks walking subsequently affects participation daily activities symptoms caused ms highly variable rehabilitation strategies often focus movements exercises improve symptoms function variable success,0.0
magnetic resonance image monitor diagnosis patients neuromyelitis optica study aimed investigate craniocerebral magnetic resonance imaging mri measurement clinical characteristics patients neuromyelitis optica nmo multiple sclerosis ms 50 patients nmo nmo group 50 patients ms ms group studied clinical manifestations brain injury morphology mri signal characteristics brain distribution characteristics related laboratory tests serum aquaporin 4 aqp4 antibody statistically analyzed,0.0
slowly expanding lesions linked multiple sclerosis progression abstract,0.0
abnormal white matter microstructure limbic system associated tuberous sclerosis complexassociated neuropsychiatric disorders conclusion disruption white matter integrity may induce underconnectivity cortical subcortical regions findings suggest tands result abnormality specific brain region rather caused connectivity dysfunction network disorder study indicates abnormal white matter connectivity including limbic system relevant tand analysis brain behavior relationship feasible approach reveal tand related,0.0
timely action multiple sclerosis abstract,0.0
lived experience multiple sclerosis patient insights guide general practitioner care background multiple sclerosis ms neurodegenerative disease symptoms varied unpredictable although effective medications treat forms ms cure many ms diagnosis means decades living chronic illness disability,0.0
phrend realworld datadriven tool supporting clinical decisions optimize treatment relapsingremitting multiple sclerosis conclusion results support usefulness phrend shared treatmentdecision process physicians patients,0.0
alterations mir1263p pou2af1 spib axis jcpyv reactivation multiple sclerosis patients receiving natalizumab natalizumab ntz can reactivate human polyomavirus john cunningham polyomavirus jcpyv latent infection lead progressive multifocal leukoencephalopathy pml ntz modulates expression microrna1263p mir1263p target genes spib pou2af1 vascular cell adhesion molecule1 vcam1 spib protein binds jcpyv regulatory region initiating early gene transcription paper aimed evaluate mir1263p soluble s vcam1 concentration spib pou2af1,0.0
phenytoin promotes proliferation oligodendrocytes enhances expression myelin basic protein corpus callosum mice demyelinated cuprizone oligodendrocyte loss myelin sheet destruction crucial characteristics demyelinating diseases phenytoin promotes proliferation endogenous neural precursor cells ventricularsubventricular zone postnatal brain help restore oligodendroglial population study aimed evaluate whether phenytoin promotes myelin recovery corpus callosum demyelinated adult mice cd1 male mice exposed demyelinating agent 02 cuprizone 8 weeks,1.0
pediatric optic neuritis prospective outcomes study twoyear results conclusions despite poor va presentation children marked improvement va 6 months maintained two years associated neurologic autoimmune diagnoses common additional episodes occurred 5 18 participants 3 relapses 2 new episodes,0.0
trends diseasemodifying therapy use patients multiple sclerosis using 10year populationbased cohort study france conclusions study provides valuable insights realworld use dmts changes operated time,0.0
current treatment systemic sclerosisassociated interstitial lung disease systemic sclerosis ssc connective tissue disease characterized immune irregularity vasculopathy excessive collagen production causes skin internal organ fibrosis although ssc often affects multiple organs systems lung involvement especially interstitial lung disease ild leading cause death disease fact different treatment options raised recent years given hope clinicians management disease,0.0
transanal irrigation neurogenic bowel dysfunction multiple sclerosis retrospective study conclusions tai effective nbd especially ms patients initial moderate nbd score improvement voiding dysfunction following tai confirms pelvic organ crosstalk need systematically consider treat bowel dysfunction ms also improve urinary symptoms,0.0
eighteenmonth safety analysis offspring breastfed mothers receiving glatiramer acetate therapy relapsing multiple sclerosis cobra study conclusion maternal intake ga breastfeeding adversely affect offspring safety outcomes assessed first 18 months life,0.0
can cognitive training reignite compensatory mechanisms advanced multiple sclerosis patients explorative morphological network approach multiple sclerosis ms shown significantly impair brain connectivity alterations functional structural networks identified associated clinical status particularly cognitive deficits aimed identify structural connectivity changes grey matter networks following cognitive rehabilitation cr persons ms pwms fifteen longstanding pwms underwent 5week crprogram 5 healthy controls hc also investigated t1weighted mri,0.0
exercise training multiple sclerosis exercise training identified neuroprotectioninducing approach patients multiple sclerosis1 however recently published reviews involving small numbers randomised controlled trials rcts concluded exercise training associated neuroprotection2 3 argue absence evidence constitute evidence absencethese rcts typically involve 16 months general exercise training exploratory wholebrain structural neuroimaging metrics patients mildtomoderate multiple sclerosis without preexisting deficits short exercise training durations insufficient yielding measurable increases wholebrain volume even powerful disease modifying therapies exert effects 16 months4 exercise programmes designed inducing brain adaptations based neurophysiological hypotheses analogous conducting regulatory disease modifying therapy trial without incorporating preclinical research rcts involve apriori hypothesised regions interest studying exercise neuroprotection disproportionately rely wholebrain exploratory structural neuroimaging generating conclusions neuroprotection5 approach embodies generalised search possible signal within cns inconsistent research demonstrating focal exerciseinduced neuroprotection patients spinal cord injury using nonvolumetric neuroimaging rcts include patients without measurable preexisting cns damage precludes inferences neuroprotection involves stopping reversing existing measurable neural damage decline rcts include followup assessments beyond 6 months longerterm followup assessments crucial evaluating protection future cns decline consistent measurement intervals disease modifying therapy trials4the absence evidence exercise training neuroprotection multiple sclerosis disappointing engaging turf protection argue poorly designed studies render generation strong conclusions moot researchers carefully evaluate evidence making sweeping inferences can stall field inquiry field will advance studies collectively include shortterm generalised exercise poorly defined multiple sclerosis cohorts exploratory wholebrain neuroimaging endpoints short time periods acknowledge shift scientific paradigm slow arduous yet encourage design stronger rcts methodically address possibility neuroprotection exercise training patients multiple sclerosisgrc received consulting fees biodelivery sciences international biogen click therapeutics genzyme genentech gw pharmaceuticals immunic kleinbuendel medday medimmune neurogenesis novartis osmotica perception neurosciences recursion cerexis rekover roche tg therapeutics payment medical writing ashfield medcomms served data safety monitoring boards alexion astrazeneca avexis biolinerx brainstorm cell therapeutics bristol myers squibb celgene csl behring galmed greenvalley pharma mapi merck merck pfizer opko biologics oncoimmune neurim novartis ophazyme protalix sanofi reata teva pharmaceuticals vielabio horizon vivius us national institutes health president pythagoras authors declare competing interests,0.0
epsteinbarr virus multiple sclerosis supporting causality epsteinbarr virus ebv herpes virus infects around 95 individuals worldwide although infection generally asymptomatic acquired childhood ebv can cause infectious mononucleosis adolescents several tumours like lymphomas nasopharyngeal carcinoma adults ebv also associated multiple sclerosis common chronic inflammatory disease cns robust evidence indicates risk multiple sclerosis nearly absent ebvseronegative individuals increases considerably ebv infection increases even infectious mononucleosis 1 furthermore people multiple sclerosis increased antibody response ebv becomes detectable years disease onset 2 3 findings suggest multiple sclerosis might develop susceptible individuals due alteration ebvhost homoeostasis ordinarily ensures lifelong pacific coexistence continuous immune surveillance healthy ebv carriers 4 date however available evidence correlative nature difficult prove ebv causes multiple sclerosis 5,0.0
ultrasensitive profiling uv mutations identifies thousands subclinical facial tumors tuberous sclerosis complex conclusion tsc facial skin can viewed harboring patchwork clonal fibroblast proliferations microfaf indolent growth small proportion develop clinically observable faf observations also expand spectrum uvrelated mutation signatures,0.0
effectiveness intravenous sedation oral surgery patient multiple sclerosis past history posterior reversible encephalopathy syndrome case report conclusion appropriate preoperative evaluation anesthetic management important maintain hemodynamics avoid recurrence pres,0.0
lymphopenia tuberculous lymphadenitis immunomodulatory agents multiple sclerosis patient followup challenging case interferonbeta ifn 1a glatiramer acetate ga firstline therapies multiple sclerosis ms immunomodulatory effects present patient developed lymphopenia tuberculous lymphadenitis treatment agents female patient present 65 year old followed ms outpatient clinics received ga 20 mg day subcutaneous injection later ifn 1a 44 g thrice weekly subcutaneous injection course treatment,0.0
clarion study design status update longterm registrybased study evaluating adverse events special interest patients relapsing multiple sclerosis newly started cladribine tablets conclusion providing information adverse events special interest longterm followup clarion will assist neurologists patients regarding treatment decisionmaking management relapsing ms,0.0
shared mechanism candidate drugs multiple sclerosis sjogrens syndrome analyzed bioinformatics based gwas transcriptome data conclusion observed shared mechanism ms ss jakstat signaling pathway played vital role may genetic molecular bases comorbidity ms ss moreover jakstat inhibitors potential therapies ms ss especially comorbidity,0.0
pdk4 inhibition ameliorates melatonin therapy modulating cerebral metabolism remyelination eae demyelinating mouse model multiple sclerosis recently showed melatonin ameliorates severity experimental autoimmune encephalomyelitis eae animal model ms however efficiency melatonin therapy associated side effects manifested slowing remyelination increasing inhibitory effects brain pyruvate dehydrogenase kinase4 pdk4 pyruvate dehydrogenase complex pdc key enzyme fatty acid fa synthesis remyelination study investigated metabolic,1.0
new developing multiple sclerosis patient using tofacitinib due alopesia areata abstract,0.0
role sex pregnancy multiple sclerosis know introduction multiple sclerosis ms prevalent women men sex patient pregnancy reported associated clinical features ms mechanism unclear,0.0
ponesimod treatment relapsing forms multiple sclerosis update emerging clinical data sphingosine 1phosphate s1p receptors bioactive lipid metabolites bind five different types receptors expressed ubiquitously human body mediate broad range biological functions targeting s1p receptors nowadays wellestablished pharmacological strategy treat multiple sclerosis ms however adverse events associated ancestor fingolimod especially terms heart conduction slow reversibility pharmacodynamics effect lymphocytes,0.0
physiotherapy interventions may relieve pain individuals central neuropathic pain systematic review metaanalysis randomised controlled trials conclusion evidence supports use noninvasive neurostimulation treatment pain secondary sci phantom limb pain beneficial pain management outcomes also identified acupuncture stroke tens multiple sclerosis mirror therapy phantom limb pain,0.0
machine learning classification multiple sclerosis patients based raw data instrumented walkway conclusions use instrumented walkway can generate rich data generally unseen clinicians researchers machine learning applied standard gait variables can discern ms patients healthy controls excellent accuracy noteworthy classifications made stronger including novel gait features toe direction hull area base support area foot length foot area,0.0
functional connectivitybased prediction global cognition motor function riluzolenaive amyotrophic lateral sclerosis patients amyotrophic lateral sclerosis als increasingly recognized multisystem disorder accompanied cognitive changes date effective therapy available als patients partly due disease heterogeneity imperfect understanding underlying pathophysiological processes reliable models can predict cognitive motor deficits needed improve symptomatic treatment slow disease progression study aimed identify individualized functional,0.0
corrigendum trpm2 contributes neuroinflammation cognitive deficits cuprizoneinduced multiple sclerosis model via nlrp3 inflammasome neurobiology disease 160 2021 105534 abstract,0.0
changes gait characteristics immediately 6minute walk test persons multiple sclerosis systematic review conclusion quantitative gait parameters deteriorated 6mwt especially pwms moderatesevere disability,0.0
pregnancy loss risk multiple sclerosis autoimmune neurological disorder nationwide cohort study conclusions nationwide study pregnancy loss significantly associated autoimmune neurological disorder,0.0
increased remyelination proregenerative microglia siponimod therapy mechanistic models background objectives siponimod oral selective sphingosine1phosphate receptor1 5 modulator approved treatment multiple sclerosis,1.0
assessment disrupted brain functional connectome tuberous sclerosis complex using restingstate fmri tuberous sclerosis complex tsc rare genetic disorder multisystem involvement tsc characterized benign hamartomas multiple organs including brain clinical phenotypes may associated abnormal functional connections aimed use restingstate functional connectivity provide findings disrupted functional brain networks tsc patients using graph theoretical analysis gta networkbased statistic nbs analysisforty tsc patients age,0.0
global status trends heart failure preserved ejection fraction period 20092020 bibliometric analysis conclusions due multidimensional bibliometric analysis study shows wide view scientific productivity related hfpef provides valuable guidance researchers interested hfpef assisting understanding research status identifying potential collaborators discovering research hotspots frontiers conducting indepth research,0.0
construction mirnaregulated drugpathway network screen drug repurposing candidates multiple sclerosis given high disability rate multiple sclerosis ms need safer effective therapeutic agents existing literature highlights prominent roles mirna ms pathophysiology nevertheless studies explored usefulness existing drugs treating ms potential mirnamodulating abilitiesthe current investigation identifies genes may exacerbate risk ms due respective mirna associations findings,0.0
lateonset ms disease course safetyefficacy dmts multiple sclerosis ms inflammatory demyelinating neurodegenerative disease central nervous system usually begins ages 20 49 years though rare cases diagnosed childhood adolescence age 18 years age 50 years later onset disease occurs 50 years older conventionally defined late onset ms loms compared classical ms loms characterized progressive course greater,1.0
synthesis cellular evaluation clickchemistry probes study biological effects alpha betaunsaturated carbonyls humans commonly exposed unsaturated carbonyls environmental toxins eg acrolein therapeutic drugs eg dimethylfumarate dmfu frontline drug treatment multiple sclerosis psoriasis compounds undergo rapid michael addition reactions amine imidazole thiol groups biological targets reaction protein cys residues major reaction pathway however cellular targets species adductome poorly,0.0
repeat infusion autologous bone marrow cells progressive multiple sclerosis phase extension study siamms ii abstractbackgroundduring safety feasibility study intravenous autologous marrow multiple sclerosis siamms intravenous infusion autologous marrow well tolerated efficacy approach explored placebocontrolled randomised controlled trial actimus nct01815632 known whether repeated infusions will required optimise benefit objective current study explore safety feasibility repeat treatment intravenous autologous bone marrow patients progressive multiple sclerosis ms methodssiamms ii prospective single centre phase extension study participants siamms study offered repeat bone marrow harvest infusion autologous unfractionated bone marrow daycase procedure primary outcome measure number adverse events secondary outcome measures included change clinical rating scales disability global evoked potential cranial magnetic resonance imaging mri resultsin total 4 6 participants siamms study repeat bone marrow harvest infusion filtered autologous marrow day case procedure well tolerated serious adverse effects additional outcome measures including clinical scales global evoked potentials cranial mri stableconclusionsiamms ii demonstrates safety feasibility repeated nonmyeloablative autologous bone marrowderived cell therapy progressive ms,1.0
repeat infusion autologous bone marrow cells progressive multiple sclerosis phase extension study siamms ii abstractbackgroundduring safety feasibility study intravenous autologous marrow multiple sclerosis siamms intravenous infusion autologous marrow well tolerated efficacy approach explored placebocontrolled randomised controlled trial actimus nct01815632 known whether repeated infusions will required optimise benefit objective current study explore safety feasibility repeat treatment intravenous autologous bone marrow patients progressive multiple sclerosis ms methodssiamms ii prospective single centre phase extension study participants siamms study offered repeat bone marrow harvest infusion autologous unfractionated bone marrow daycase procedure primary outcome measure number adverse events secondary outcome measures included change clinical rating scales disability global evoked potential cranial magnetic resonance imaging mri resultsin total 4 6 participants siamms study repeat bone marrow harvest infusion filtered autologous marrow day case procedure well tolerated serious adverse effects additional outcome measures including clinical scales global evoked potentials cranial mri stableconclusionsiamms ii demonstrates safety feasibility repeated nonmyeloablative autologous bone marrowderived cell therapy progressive ms,1.0
antibodies blood coagulation components implicated patients multiple sclerosis abstractbackgroundthe strong link innate immunity thrombosis coagulation recently investigated light antibodies directed serine proteases coagulation pathway antibodies proposed contributing factors venous thromboembolism development key molecules initiation signaling inflammatory pathways neuroinflammatory diseases preliminary studies multiple sclerosis ms progression characteristics reactivity antibodies coagulant components limited considering development thrombosis early onset ms study aimed detect antibodies coagulant components ms evaluate possible association clinical profile diseasemethoda crosssectional study carried identify antibodies factor f viia thrombin prothrombin fxa fxii plasmin protein c serum samples 167 patients ms 40 healthy controls using enzymelinked immunosorbent assay statistical analysis performed evaluation dataresultsthe analysis revealed significantly higher prevalence igg ms patients n72 43 compared hcs n8 20 p001 specifically elevated antifviia n19 114 mean activity p00001 antifxii n12 72 mean activity p0001 antiplasmin n20 12 mean activity p001 levels observed patients compared controls additionally highest scores clinical characteristics like expanded disability status scale ms severity score linked igg seropositivity thrombin whilst antifxii levels corresponded lowest disease progressionconclusionthe findings study illustrate presence antibodies serine proteases coagulation cascade ms demonstrate association antibody activity disease progression particular thrombin igg seropositivity demonstrated associated worse outcomes severe disease phenotype observations suggest implication antibodies patient monitoring prognosis evaluation may elucidate inflammatory cascades antibodies act key mediators,0.0
proinflammatory cd20sup+ sup t cells contribute cnsdirected autoimmunity origin function cd20 + t cells poorly understood characterized cd20 + t cells mice humans investigated affected anticd20 antibody treatment report murine cd20 + t cells unable endogenously express b cell lineage marker cd20 development cd20 + t cells rodents requires presence cd20expressing b cells results demonstrated murine human t cells acquire cd20 b cells via,0.0
effect p38 mitogenactivated protein kinase signaling cascade radiation biodosimetry radiation biodosimetry based transcriptomic analysis peripheral blood valuable tool detect radiation exposure radiological nuclear event obtain useful biological information predict tissue organismal injury however confounding factors including chronic inflammation immune suppression can potentially obscure predictive power method members p38 mitogenactivated protein kinase mapk family respond proinflammatory signals,0.0
safety accuracy homebased ballistic resistance training people neurological conditions conclusion homebased ballistic resistance exercises safe accuracy low several ballistic resistance exercises higher selfselected walking speeds associated accurate performance,0.0
disseminated nocardiosis cladribine treatment relapsing remitting multiple sclerosis case report abstract,0.0
csf1 maintains pathogenic homeostatic myeloid cells central nervous system autoimmune neuroinflammation significancemultiple sclerosis ms animal model experimental autoimmune encephalomyelitis eae autoimmune diseases characterized accumulation myeloid cells central nervous system cns harmful beneficial myeloid cells present eae ms goal ms therapy preferentially remove harmful myeloid cells receptor csf1 csf1r found myeloid cells important survival csf1r can bind two ligands csf1 il34,1.0
effect retinoic acid neurovascular unit review retinoic acid metabolic product derived vitamin acting nuclear level maintain proper transcriptional activity moreover molecule contributes development maturation cerebral vascular system playing pivotal role development maintenance neurovascular unit integrity physiological structure comprised glial cells vascular cells neurons ensuring correct function bloodbrain barrier last instance,0.0
progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome discontinuation fingolimod progressive multifocal leukoencephalopathy pml rare complication immunosuppressive treatment ms patients immune reconstitution inflammatory syndrome iris appears withdrawal certain drugs natalizumab ntz fingolimod development pmliris ntz treatment described diagnosis made clinical radiological criteria determination john cunningham virus csf present clinical case patient ms,0.0
effect selfacupressure quality life physical cognitive function relapsing remitting multiple sclerosis patients randomized controlled study conclusion found selfacupressure effective improving physical function cognitive function quality life rrms patients additionally selfacupressure feasible accessible inexpensive method disease management multiple sclerosis needs treated supported continuously,1.0
stillbirth due sarscov2 placentitis without evidence intrauterine transmission fetus association maternal risk factors conclusions sarscov2 placentits occurred uncommonly covid19affected pregnancies nonvaccinated mothers extensive caused fetal demise evidence transplacental fetal infection thrombophilia prenatally detected iugr emerged independent predisposing factors potentially lethal sarscov2 placentitis article protected copyright rights reserved,0.0
dementia associated medial temporal atrophy even accounting neuropathologies brain atrophy associated degenerative neuropathologies clinical status dementia whether dementia associated atrophy independent neuropathologies known study examined pattern atrophy associated dementia accounting common dementiarelated neuropathologies used data national alzheimers coordinating center n 129 alzheimers disease neuroimaging initiative n 47 participants suitable vivo,0.0
quot dry oral ocular manifestations autoantibodies characteristic primary sjgren#39 s syndrome multiple sclerosisquot abstractintroductionthe relationship primary sjgren syndrome pss demyelinating diseases still well understood diseases seem coexist amidst autoimmunity raising questions clinical characteristics relationship immunomodulatory treatment possible common immunological background underlying pathogenesisobjectivecalculate frequency dry oral ocular manifestations autoantibodies characteristic primary sjgrens syndrome multiple sclerosismethods202 patients multiple sclerosis answered questionnaire identify complaints xerostomia xerophthalmia according diagnostic criteria primary sjgrens syndrome 43 answered positively least one question 27 comorbidities used drugs cause dry symptoms excluded 16 patients selected examinations oral ocular serum antiro ssa autoantibody evaluationresultseleven 6875 patients complained xerostomia 14 875 xerophthalmia sialometry01ml min observed three 188 13 patients underwent minor salivary gland biopsy histopathological examination focal score1 three 231 schirmer test was5mm 5min four 25 lyssamine green fluorescein dye score was5 three 188 antiro ssa10 ui mm two 125 three 1 49 patients met current criteria primary sjgrens syndromeconclusionspatients ms may report xerostomia xerophthalmia even absence comorbidities use medications capable causing symptoms may fulfill diagnostic criteria pss study frequency pss according current criteria within range observed literature older criteria question remains whether association diseases fortuitous whether pathogenic link,1.0
prevalence multiple sclerosis treatment utilization large highly diverse population abstractbackgrounddespite advances algorithms identifying people ms pwms large data sets limited data exists regional prevalence prevalence care minority populationsobjectivesto report 7year 01 01 2012 12 31 2018 prevalence demographics ms diseasemodifying therapy dmt utilization large diverse populationmethodsthis retrospective analysis used oneflorida data trust captures health data 15 million floridians across 10 constituent organizations validated algorithm identified subjects ms dmts identified using rxnorm concept unique identifiers national drug codes results stratified across age sex raceethnicity locationresultsof 6 638 649 adults database algorithm identified 9 681 pwms overall prevalence per 100 000 14583 ms prevalence considerable women races ethnicities ranging 13886 25376 per 100 000 526 pwms one dmt prescription dmt prescription likely hispanic pwmsconclusionprevalence analysis oneflorida data trust revealed substantial burden disease women races ethnicities variation treatment utilization among demographic subgroups underscores need additional studies assess health care disparities ms population level,0.0
quot dry oral ocular manifestations autoantibodies characteristic primary sjgren#39 s syndrome multiple sclerosisquot abstractintroduction relationship primary sjgren syndrome pss demyelinating diseases still well understood diseases seem coexist amidst autoimmunity raising questions clinical characteristics relationship immunomodulatory treatment possible common immunological background underlying pathogenesisobjective calculate frequency dry oral ocular manifestations autoantibodies characteristic primary sjgrens syndrome multiple sclerosis methods 202 patients multiple sclerosis answered questionnaire identify complaints xerostomia xerophthalmia according diagnostic criteria primary sjgrens syndrome 43 answered positively least one question 27 comorbidities used drugs cause dry symptoms excluded 16 patients selected examinations oral ocular serum antiro ssa autoantibody evaluationresults eleven 6875 patients complained xerostomia 14 875 xerophthalmia sialometry 01 ml min observed three 188 13 patients underwent minor salivary gland biopsy histopathological examination focal score 1 three 231 schirmer test 5millimeters 5minutes four 25 lyssamine green fluorescein dye score 5 three 188 antiro ssa 10 ui milimeters two 125 three 1 49 patients met current criteria primary sjgrens syndromeconclusions patients ms may report xerostomia xerophthalmia even absence comorbidities use medications capable causing symptoms may fulfill diagnostic criteria pss study frequency pss according current criteria within range observed literature older criteria question remains whether association diseases fortuitous whether pathogenic link,1.0
association common variable immunodeficiency rare complex connective tissue musculoskeletal diseases systemic literature review conclusions concurrence cvid complex connective tissue musculoskeletal diseases especially ss iim ssc relapsing polychondritis rare relevant measurements iglevels performed initiation immunosuppressive therapy allow differentiation primary secondary igdeficiency substitute ig necessary,0.0
magnolol prevented brain injury modulation nrf2dependent oxidative stress apoptosis plpinduced mouse model multiple sclerosis multiple sclerosis ms immunemediated chronic inflammatory demyelinating disease central nervous system cns aim current study investigate effects magnolol experimental autoimmune encephalomyelitis eae model ms female mice magnolol 01 1 10 mg kg administered daily 21 days immunization mice magnolol postimmunization treatment significantly reversed clinical scoring eaeassociated pain parameters motor,1.0
effect lesion filling brain network analysis multiple sclerosis using structural magnetic resonance imaging conclusion lesion filling might reduce variability across subjects resulting increased detection rate network alterations ms also induces significant artefacts therefore applied cautiously especially individuals higher lesions loads,0.0
retinal imaging optical coherence tomography multiple sclerosis novel aspects optical coherence tomography oct increasing interest clinical assessment multiple sclerosis ms patients beyond scope clinical studies narrative review discuss novel changes oct parameters acute optic neuritis disease course ms patients oct images document changes retinal layers episode acute optic neuritis can therefore provide valuable insights pathophysiology moreover ms patients show progredient,0.0
identification potential biomarkers peripheral blood mononuclear cells relapsingremitting multiple sclerosis patients multiple sclerosis ms described immune disorder inflammation neurodegeneration relapsingremitting ms rrms one common types ms diagnostic manner disorder typically includes usage magnetic resonance imaging mri however always precise diagnostic method identification molecular biomarkers rrms body fluids samples compared healthy subjects can useful indicate normal pathogenic biological,0.0
neuropathic pain neurologic disorders narrative review neuropathic pain defined painful condition caused neurological lesions diseases sometimes neurological disorders may also associated neuropathic pain can challenging manage example multiple sclerosis ms may cause chronic centralized painful symptoms due nerve damage chronic neuropathic pain syndromes may occur form poststroke pain spinal cord injury pain central pain syndromes chronic neuropathic pain associated,0.0
natural history newonset inflammatory bowel disease among patients multiple sclerosis abstract,0.0
pharmaceutical perspective neuropathic pain management primary care providers neuropathic pain np chronic condition affects 1 general population globally several conditions chronic diabetes herpes zoster hz cancer hiv stroke multiple sclerosis physical compression damage nerves certain surgical procedures can lead neuropathy related pain condition difficult treat traditional analgesic drugs typically nontraditional analgesics used treating pain condition antidepressants,0.0
noncoding rnas regulation bloodbrain barrier functions central nervous system disorders bloodbrain barrier bbb essential component neurovascular unit controls exchanges various biological substances blood brain bbb damage common feature different central nervous systems cns disorders plays vital role pathogenesis diseases noncoding rnas ncrnas micrornas mirnas long noncoding rna lncrnas circular rnas circrnas important regulatory rna molecules involved,0.0
systemlevel variation multiple sclerosis diseasemodifying therapy utilization findings multiple sclerosis continuous quality improvement research collaborative conclusion systemlevel effects ms treatment outcomes previously studied findings contribute initial evidence concerning systemlevel variation dmt utilization results suggest systemlevel variation dmt utilization ie adjusting individual level factors ms center location care person ms engages care influences dmt treatment choices resulting lack standardization dmt management continued research improvement,0.0
locus specific reduction l1 expression cortices individuals amyotrophic lateral sclerosis activation dysregulation retrotransposons identified cns individuals fatal neurodegenerative disorder amyotrophic lateral sclerosis als includes elements multiple different families subfamilies retrotransposons however limited knowledge specific loci expression occurs als long interspersed element1 l1 autonomous retrotransposon human genome members family,0.0
incidence prevalence multiple sclerosis malmo southern sweden conclusions first populationbased epidemiological study skne southwestern part sweden showing high incidence prevalence found lower incidence expected according previous nationwide figures probably due methodological differences studies findings support presence northsouth gradient ms prevalence sweden,0.0
tractometry principal component analysis white matter tract network structure relationships cognitive function relapsingremitting multiple sclerosis understanding brain changes underlying cognitive dysfunction key priority multiple sclerosis ms improve monitoring treatment debilitating symptom functional connectivity network changes associated cognitive dysfunction less well understood changes normal appearing white matter relate cognitive symptoms white matter tracts network structure expected tracts within network share susceptibility ms pathology,0.0
humoral response sarscov2 vaccines ms patients case series exploring impact dmt lymphocyte count immunoglobulins vaccine type abstractbackground objectivescertain disease modifying therapies may negatively impact humoral response sarscov2 vaccines many ms related clinical demographic immunological characteristics can also affect vaccine response fully explored study aimed investigate potential correlations clinical demographic immunological variables ms patients postvaccination spike protein antibody positivity rates levelsmethodspatients ms related neuroimmunological disorders requested verification immune response sarscov2 vaccine tested spike protein antibody january october 2021 performed exploratory analysis compare patients positive versus negative spike protein antibodyresultsfifty patients mean age 53 12 78 females included 29 patients positive postvaccination spike protein antibody 58 21 negative antibody 42 patients negative antibody likely bcell therapy 86 vs 31 p001 positive patients likely fumarate 31 vs 48 p03 thirty percent positive patients fumarate therapy mild lymphopenia differences existed groups gender age race disease phenotype vaccine brand lymphocyte counts among patients bcell therapy 33 positive spike protein antibody association detectable cd19 cells time vaccination positive humoral response vaccination p0049 relationship subgroups terms vaccine timing relative bcell therapy dose hypogammaglobulinemia associated seroconversion rates however associated decreased quantitative spike protein antibody levels p0045 discussionbcell therapy associated negative humoral response sarscov2 vaccines patients bcell depleting therapy detectable cd19 counts time vaccination associated positive humoral response relationship hypogammaglobinemia seroconversion rate however associated decreased spike protein antibody levels fumarates associated positive humoral response even presence mild lymphopenia,0.0
humoral response sarscov2 vaccines ms patients case series exploring impact dmt lymphocyte count immunoglobulins vaccine type abstractbackground objectivescertain disease modifying therapies may negatively impact humoral response sarscov2 vaccines many ms related clinical demographic immunological characteristics can also affect vaccine response fully explored study aimed investigate potential correlations clinical demographic immunological variables ms patients postvaccination spike protein antibody positivity rates levelsmethodspatients ms related neuroimmunological disorders requested verification immune response sarscov2 vaccine tested spike protein antibody january october 2021 performed exploratory analysis compare patients positive versus negative spike protein antibodyresultsfifty patients mean age 53 12 78 females included 29 patients positive postvaccination spike protein antibody 58 21 negative antibody 42 patients negative antibody likely bcell therapy 86 vs 31 p001 positive patients likely fumarate 31 vs 48 p03 thirty percent positive patients fumarate therapy mild lymphopenia differences existed groups gender age race disease phenotype vaccine brand lymphocyte counts among patients bcell therapy 33 positive spike protein antibody association detectable cd19 cells time vaccination positive humoral response vaccination p0049 relationship subgroups terms vaccine timing relative bcell therapy dose hypogammaglobulinemia associated seroconversion rates however associated decreased quantitative spike protein antibody levels p0045 discussionbcell therapy associated negative humoral response sarscov2 vaccines patients bcell depleting therapy detectable cd19 counts time vaccination associated positive humoral response relationship hypogammaglobinemia seroconversion rate however associated decreased spike protein antibody levels fumarates associated positive humoral response even presence mild lymphopenia,0.0
evolution increases primates brain complexity extending rbfox1 splicing activity lsd1 modulation recent branching 100 mya mammalian evolutionary tree enhanced brain complexity functions putative cost increased emotional circuitry vulnerability thus better understand psychopathology burden modern society novel approaches exploit evolutionary aspects psychiatricrelevant molecular pathways handful genes nowadays tightly associated psychiatric disorders among neuronalenriched rbfox1 modifies activity synaptic regulators response neuronal activity keeping excitability within healthy domains dissect higher primatesrestricted interaction rbfox1 transcriptional corepressor lysine specific demethylase 1 lsd1 kdm1a single nucleotide variation aa ag lsd1 gene appeared higher primates humans endowing rbfox1 ability promote alternative usage novel 3 ag splice site extends lsd1 exon e9 upstream intron e9long exon e9long regulates lsd1 levels nonsensemediated mrna decay reintroduction archaic lsd1 variant aa abolishes e9long splicing novel 3 ag splice site necessary rbfox1 control lsd1 levels lsd1 homeostatic immediate early genes iegs regulator playing relevant part environmental stressresponse primates humans inclusion lsd1 rbfox1 target provides rbfox1 additional ability regulate iegs data together extensive rbfox1 involvement psychiatric disorders stressdependent regulation male mice suggest rbfox1lsd1iegs axis evolutionary recent psychiatricrelevant pathway notably outside nervous system rbfox2dependent lsd1 modulation candidate deregulated mechanism cancersignificance statementto better understood anxiety depression need large human genetics studies aimed resolving often ambiguous aberrant neuronal pathomechanisms impact corticolimbic circuitry physiology several genetic associations alternative splicing regulator rbfox1 psychiatric conditions suggest homeostatic unbalance neuronal signature psychopathology move step forward characterizing diseaserelevant higher primatesspecific pathway rbfox1 acquires ability regulate neuronal levels lysine specific demethylase 1 epigenetic modulator environmental stress response thus two brainenriched enzymes independently shown homeostatically protect neurons clear readout terms emotional behavior lower mammals establish higher primates humans new functional cooperation enhancing complexity environmental adaptation stress vulnerability,0.0
selected factors determining failure undertake physical activity patients multiple sclerosis poland conclusion physicians relatively rarely encourage patients ms undertake hte opa patients perform hte primarily fears health deterioration fatigue undertaking hte influenced age undertaking forms physical activity type ms actions taken popularize hte opa especially hte among young patients,0.0
neutralizing antibody responses sarscov2 vaccinated people multiple sclerosis background patients multiple sclerosis pwms often treated disease modifying therapies dmt immunomodulatory effects particular concern following development several vaccines combat coronavirus disease 19 covd19 potentially fatal illness caused sarscov2 objectives determine efficacy sarscov2 vaccination pwms impact disease modifying therapies dmt vaccine response methods prospective longitudinal study pwms longitudinal serum samples obtained prior sarscov2 mrna vaccination novel neutralizing antibody nab assay used determine nabs titres sarscov2 spike results observed 1 pwms bcell depleting therapies exhibited reduced response vaccination compared pwms correlating time last anticd20 infusion 2 prior covid19 illness dmt category pyramidal function significant predictors vaccine responsiveness 3 circulating absolute lymphocyte count alc igg levels correlated nab levels conclusions demonstrate pwms exhibit reduced nab response mrna vaccination dependent dmt status identify predictive biomarkers vaccine efficacy conclude additional vaccination strategies may necessary achieve protective immunity pwms keywords covid19 multiple sclerosis diseasemodifying therapies immunology vaccination,0.0
delve multiple sclerosis ms lesion exploration modified attention unet ms lesion segmentation brain mri multiple sclerosis ms central nervous system cns disease magnetic resonance imaging mri system can detect segment lesions artificial neural networks anns recently reached noticeable performance finding ms lesions mri unet attention unet two successful anns field ms lesion segmentation work proposed framework segment ms lesions fluidattenuated inversion recovery flair t2 mri images modified unet,0.0
correction prevalence predictors bowel dysfunction large multiple sclerosis outpatient population italian multicenter study abstract,0.0
physiotherapist participant perspectives randomizedcontrolled trial physiotherapistsupported online vs paperbased exercise programs people moderate severe multiple sclerosis abstract purpose gap research best support exercise moderate severe ms objective study share perspectives people living ms physiotherapists experiences randomized clinical trial online physiotherapy vs active comparator methods semistructured exit interviews conducted volunteer participants online comparator arms trial focus groups held study physiotherapists transcripts analyzed using reflexive thematic analysis results perspectives participants ms yielded three themes usability program utility program motivation participate visual dexterity impairments limited usability online program opportunity pushed valued participants trial arms motivation exercise variable participants desired periodic facetoface contact physiotherapists perspectives trial physiotherapists yielded similar complementary findings concerning usability utility conclusions participants ms physiotherapists found online physiotherapy platform useful supporting exercise yet identified limitations appeal online platforms increased since pandemic will important consider needs people moderate severe ms trial registration number nct03039400implications rehabilitationpeople moderatetosevere ms physiotherapists involved clinical trial found online physiotherapy useful supporting exercise physiotherapists participants using online program desired improved platform accommodations people living ms visual dexterity impairmentsphysiotherapists people living ms online exercise program comparator groups perceived need facetoface contact opportunities build therapeutic allianceperspectives prescribing physiotherapists people living ms supporting exercise online may practice implications postpandemic keywords telerehabilitation exercise internetbased intervention multiple sclerosis ms patient preference physiotherapy,0.0
epigenetic modifications pathogenesis systemic sclerosis systemic sclerosis rare chronic autoimmune disease mainly manifests immune disorders vascular damage progressive fibrosis etiology ssc complex involves multiple factors genetic environmental factors involved pathogenesis one molecular mechanisms environmental factors epigenetic regulation plays important role occurrence development systemic sclerosis involves dna methylation histone modification,0.0
role effectiveness augmented reality patient education systematic review literature abstract objectives provide overview existing research concerning use effects ar patient education methods following prisma guidelines four electronic databases systematically searched inclusion criteria empirical studies using type ar intervention patient education across medical specialties quality assessment retrieved literature carried results ten papers comprising 788 patients identified included randomized controlled trial rct n 3 nonrandomized controlled trial n 3 beforeandafter study n 3 qualitative survey n 1 retrieved literature showed highly heterogeneous studied population included patients suffering diverse spectrum chronic diseases eg prostate cancer diabetes mellitus multiple sclerosis epilepsy quantitative results indicated use ar positive effect knowledge retention patient satisfaction qualitative findings suggested patients liked technology felt comfortable use educational purposes quality retrieved results shown moderate low conclusion limited evidence topic suggests possible potential ar patient education practice implication research using highquality study designs evidencebased interventions needed fully appreciate value ar patient education keywords ar augmented reality chronic disease knowledge retention patient education patient satisfaction systematic review,0.0
prospective memory multiple sclerosis clinical utility miami prospective memory test objective multiple sclerosis ms chronic inflammatory disease central nervous system frequently affects cognition persons ms pwms complain difficulties prospective memory pm capacity remember perform intended action appropriate moment future objective study assess clinical utility miami prospective memory test mpmt detecting pm deficits ms test brief easy administer accessible,0.0
impaired metabolism oligodendrocyte progenitor cells axons demyelinated lesion aged cns key pathology multiple sclerosis ms comprises demyelination axonal damage neuronal loss ms develops progressive phase essentially untreatable identifying new targets axons oligodendrocyte progenitor cells opcs rejuvenating aged opcs holds promise unmet medical need summarize recent evidence showing mitochondria axons opcs impaired lipid metabolism opcs within demyelinated lesion,1.0
comparative study capability mscs isolated different human tissue sources differentiate neuronal stem cells dopaminergiclike cells conclusion results indicate protocol utilized successfully differentiated bm wjmscs nsclike cells wjmscs possess higher potential transdifferentiate nsc dopaminergiclike cells thus might indicate protocol can used induce msc neuronal lineage provides additional alternative source cells used neurological cellbased therapies,0.0
il33 regulatory t cell axis suppresses skin fibrosis fibrosis pathological hallmark systemic sclerosis ssc deadly autoimmune disease affecting connective tissues multiple organs however immune mechanisms underlying fibrosis ssc remain unclear determine initiating immune pathway fibrosis investigated role type 2 alarmin cytokines mouse model skin fibrosis wildtype wt mice received subcutaneous bleomycin blm injections developed skin fibrosis accompanied elevated interleukin,0.0
translational advances melanocortin drugs integrating biology chemistry genetics melanocortin receptors emerged important targets unusual versatility widespread distribution multiple tissues eg skin adrenal glands brain immune cells exocrine glands together variety physiological processes control pigmentation cortisol release satiety mechanism inflammation secretions place family receptors genuine therapeutic targets many disorders review focuses journey development,0.0
reallife evidence treatment alemtuzumab patients diagnosed relapsingremitting multiple sclerosis colombia background physical disability cognitive impairment depression fatigue poorly understood latin american patients multiple sclerosis following alemtuzumab infusionobjectivesto describe sustained changes physical disability average 22month followup period alemtuzumab infusion demographical clinical variables modulate change edss adverse events changes cognition fatigue depressive symptoms average 15month followup periodmethod retrospective cohort observational study following review medical records 23 patients relapsing remitting multiple sclerosis treated alemtuzumab identified 17 baseline neuropsychological assessment 12 least one followup neuropsychological assessmentresultsmost patients presented low level physical disability depression fatigue cognitive impairment pronounced processing speed visuospatial memory baseline fifteen 23 652 patients showed disability improvement 7 301 patients remained stable 1 43 patient worsened change influenced age baseline disability score twenty 87 patients remained free clinical relapses performance improved bvmtr visual memory test 9 75 remained stable improved bicams 666 perceived decreased fatigue dfis adverse events occurred 7 301 patients common opportunistic infections 2 86 patients one 29yearold patient presented papillary thyroid carcinoma infusion second course alemtuzumabconclusionsresults suggest treatment alemtuzumab beneficial impact disability cognitive impairment perception fatigue percentage type adverse events observed cohort similar reported reallife studies,1.0
mesenchymal stem cell therapy cognition ms preliminary findings phase ii clinical trial abstractbackgroundmesenchymal stem cell msc therapies evaluated multiple sclerosis ms possible neural repair date potential benefits cognition received little attention objective current study comprehensively evaluate cognition msc therapy ms part doubleblind phase ii clinical trialmethodstwentyeight individuals confirmed diagnosis ms randomly assigned two study arms cognition evaluated using expanded minimal assessment cognitive function multiple sclerosis macfims battery battery administered week 0 week 24 week 48 results analysed group individual levelresultsno detectable effect mscmediated neural repair noted shortterm respect cognition although cognitive stability improvement observed decline noted cognitive areas immediately following procedure week 24 though temporary performance returning baseline levels week 48conclusionswhile msc therapy lead improvement cognition least shortterm neither procedure lasting deleterious effects current findings lend support safety feasibility msc therapy potentially viable treatment option individuals ms,1.0
reallife evidence treatment alemtuzumab patients diagnosed relapsingremitting multiple sclerosis colombia summarybackgroundphysical disability cognitive impairment depression fatigue poorly understood latin american patients multiple sclerosis following alemtuzumab infusionobjectivesto describe sustained changes physical disability average 22month followup period alemtuzumab infusion demographical clinical variables modulate change edss adverse events changes cognition fatigue depressive symptoms average 15month followup periodmethodretrospective cohort observational study following review medical records 23 patients relapsing remitting multiple sclerosis treated alemtuzumab identified 17 baseline neuropsychological assessment 12 least one followup neuropsychological assessmentresultsmost patients presented low level physical disability depression fatigue cognitive impairment pronounced processing speed visuospatial memory baseline fifteen 23 652 patients showed disability improvement 7 301 patients remained stable 1 43 patient worsened change influenced age baseline disability score twenty 87 patients remained free clinical relapses performance improved bvmtr visual memory test 9 75 remained stable improved bicams 666 perceived decreased fatigue dfis adverse events occurred 7 301 patients common opportunistic infections 2 86 patients one 29yearold patient presented papillary thyroid carcinoma infusion second course alemtuzumabconclusionsresults suggest treatment alemtuzumab beneficial impact disability cognitive impairment perception fatigue percentage type adverse events observed cohort similar reported reallife studies,0.0
towards imaging criteria best differentiate ms nmosd mogad large multiethnic population different clinical scenarios abstractbackgroundthe 1 3 brain magnetic resonance imaging mri criteria including 1 lesion adjacent lateral ventricle inferior temporal lobe 2 juxtacortical lesion 3 dawson fingertype lesion shown distinguish multiple sclerosis ms antibodymediated conditions large multicentre study aimed assess criteria perform 1 different onset phenotypes 2 distinct ethnic groups 3 absence myelin oligodendrocyte glycoprotein antibody mogab associated disease mogad typical fluffy infratentorial fit lesions longitudinally extensive transverse myelitis letm lesions added features 2 4 3 5 criteria respectively methods577 patients ms n332 aquaporin4 antibody aqp4ab neuromyelitis optica spectrum disorder nmosd n196 mogad n49 recruited 6 international centres buenos aires sao paolo maracaibo goyang oxford milan imaging scans obtained disease onset relapseresultsadding absence fit lesions increased specificity 1 3 criteria vs aqp4ab nmosd 847 872 vs mogad 857 939 without compromising sensitivity 86 particular presenting brain brainstem attacks 2 4 significantly higher specificity 1 3 85 vs 80 aqp4ab nmosd 889 vs 722 mogad positive predictive values 1 3 criteria ms lowest asian patients 848vs 991 white significantly increased adding criteria 941 3 5 conclusionthe 1 3 criteria perform well discriminating ms nmosd mogad regardless ethnic background clinical scenario adding absence fit lesions increases specificity presenting brain brainstem symptoms,1.0
towards imaging criteria best differentiate ms nmosd mogad large multiethnic population different clinical scenarios backgroundthe 1 3 brain magnetic resonance imaging mri criteria including 1 lesion adjacent lateral ventricle inferior temporal lobe 2 juxtacortical lesion 3 dawson fingertype lesion shown distinguish multiple sclerosis ms antibodymediated conditions large multicentre study aimed assess criteria perform 1 different onset phenotypes 2 distinct ethnic groups 3 absence myelin oligodendrocyte glycoprotein antibody mogab associated disease mogad typical fluffy infratentorial fit lesions longitudinally extensive transverse myelitis letm lesions added features 2 4 3 5 criteria respectively methods577 patients ms n332 aquaporin4 antibody aqp4ab neuromyelitis optica spectrum disorder nmosd n196 mogad n49 recruited 6 international centres buenos aires sao paolo maracaibo goyang oxford milan imaging scans obtained disease onset relapseresultsadding absence fit lesions increased specificity 1 3 criteria vs aqp4ab nmosd 847 872 vs mogad 857 939 without compromising sensitivity 86 particular presenting brain brainstem attacks 2 4 significantly higher specificity 1 3 85 vs 80 aqp4ab nmosd 889 vs 722 mogad positive predictive values 1 3 criteria ms lowest asian patients 848 vs 991 white significantly increased adding criteria 941 3 5 conclusionthe 1 3 criteria perform well discriminating ms nmosd mogad regardless ethnic background clinical scenario adding absence fit lesions increases specificity presenting brain brainstem symptoms,1.0
mesenchymal stem cell therapy cognition ms preliminary findings phase ii clinical trial backgroundmesenchymal stem cell msc therapies evaluated multiple sclerosis ms possible neural repair date potential benefits cognition received little attention objective current study comprehensively evaluate cognition msc therapy ms part doubleblind phase ii clinical trialmethodstwentyeight individuals confirmed diagnosis ms randomly assigned two study arms cognition evaluated using expanded minimal assessment cognitive function multiple sclerosis macfims battery battery administered week 0 week 24 week 48 results analysed group individual levelresultsno detectable effect mscmediated neural repair noted shortterm respect cognition although cognitive stability improvement observed decline noted cognitive areas immediately following procedure week 24 though temporary performance returning baseline levels week 48conclusionswhile msc therapy lead improvement cognition least shortterm neither procedure lasting deleterious effects current findings lend support safety feasibility msc therapy potentially viable treatment option individuals ms,1.0
reallife evidence treatment alemtuzumab patients diagnosed relapsingremitting multiple sclerosis colombia background physical disability cognitive impairment depression fatigue poorly understood latin american patients multiple sclerosis following alemtuzumab infusionobjectivesto describe sustained changes physical disability average 22month followup period alemtuzumab infusion demographical clinical variables modulate change edss adverse events changes cognition fatigue depressive symptoms average 15month followup periodmethod retrospective cohort observational study following review medical records 23 patients relapsing remitting multiple sclerosis treated alemtuzumab identified 17 baseline neuropsychological assessment 12 least one followup neuropsychological assessmentresultsmost patients presented low level physical disability depression fatigue cognitive impairment pronounced processing speed visuospatial memory baseline fifteen 23 652 patients showed disability improvement 7 301 patients remained stable 1 43 patient worsened change influenced age baseline disability score twenty 87 patients remained free clinical relapses performance improved bvmtr visual memory test 9 75 remained stable improved bicams 666 perceived decreased fatigue dfis adverse events occurred 7 301 patients common opportunistic infections 2 86 patients one 29yearold patient presented papillary thyroid carcinoma infusion second course alemtuzumabconclusionsresults suggest treatment alemtuzumab beneficial impact disability cognitive impairment perception fatigue percentage type adverse events observed cohort similar reported reallife studies,1.0
vitamin b complex experimental autoimmune encephalomyelitis attenuation clinical signs gut microbiota dysbiosis present study aimed investigate neuroprotective effects vitamin b complex b1 b2 b3 b5 b6 b12vbc studying changes femoral nerve quadriceps muscle popliteal lymph nodes gut microbiota rat model multiple sclerosis experimental autoimmune encephalomyelitis eae vbc treatment attenuated clinical signs eae disease reduced duration eae thereby contributing faster recovery vbctreated eae rats,1.0
role diet interventions multiple sclerosis review multiple sclerosis ms chronic autoimmune disease central nervous system cns characterized inflammation neurodegeneration prominent clinical features include visual loss sensorimotor symptoms mainly affects young age factors affecting pathogenesis genetic environmental including viruses smoking obesity nutrition current research provides evidence diet may influence ms onset course quality life,0.0
herpesvirus infections kir2dl2positive multiple sclerosis patients mechanisms triggering autoimmunity multiple sclerosis ms possible relationship viral infection evidenced clinical evidence implication infectious events disease onset relapse aim research study human herpesvirus hhvs infections might dysregulate innate immune system impact autoimmune responses ms analyzed 100 ms relapsing remitting patients remission phase 100 healthy controls 100 subjects inflammatory neurological,0.0
managing communication changes persons multiple sclerosis findings qualitative focus groups conclusions implications study identified wide range unmet wants needs pwms related communication changes participants wanted improved collaborative partnerships healthcare professionals better manage communication changes example healthcare professionals ask pwms potential communication changes provide education make appropriate referrals education information provision focus communication changes ms factors,0.0
predictive mri biomarkers msa critical review background objectives critical review explore potential use mri measurements prognostic biomarkers multiple sclerosis ms patients conventional measurements novel techniques magnetization transfer diffusion tensor proton spectroscopy mri materials methods authors individually comprehensively reviewed aspects listed pubmed medline google scholar results numerous mri metrics,0.0
gamcovidvac sputnik v pfizerbiontech vaccines adverse events following immunization patients affected parkinsons disease multiple sclerosis longitudinal study republic san marino covid19 vaccination campaign used gamcovidvac pfizerbiontech vaccines assess adverse events following immunization aefis approximately 6000 vaccine recipients monitored rocca study including subgroups parkinsons disease pd multiple sclerosis ms purpose study evaluate shortterm aefis 1month followup conducted longitudinal study using active surveillance evaluate safety profiles,0.0
alterations subset cytokine profile peripheral t helper cells pbmcs multiple sclerosis patients individuals ms risk snps near genes cyp27b1 cyp24a1 t helper cells play important role aetiology multiple sclerosis ms vitamin d antiinflammatory effect t helper cells can affect onset pathogenesis ms two genes metabolic vitamin d pathway expressed activated t helper th cells identified ms risk genes genomewide association studies cyp27b1 25 oh d 3 1alphahydroxylase cyp24a1 1 25 oh 2 d 3 24alphahydroxylase therefore hypothesize ms risk alleles around,0.0
prevalence severity outcomes risk factors covid19 multiple sclerosis observational study middle east crosssectional hospital recordsbased study conducted evaluate prevalence severity outcomes identify demographic clinical risk factors coronavirus disease covid19 patients ms study conducted multiple clinics oman kuwait united arab emirates uae march 2020 february 2021 association patient demographics ms disease characteristics use diseasemodifying therapies outcomes covid19 illness,0.0
microbiota iga multiple sclerosis multiple sclerosis ms neuroinflammatory disease characterized immune cell infiltration central nervous system destruction myelin sheaths alterations gut bacteria abundances present ms patients mouse models neuroinflammation depletion microbiota results amelioration symptoms gavage ms patient microbiota exacerbates disease inflammation via th17 cells hand depletion b cells using anticd20 efficient,1.0
botanicallyderived delta 9 tetrahydrocannabinol cannabidiol 11 combination modulate tolllike receptor 3 4 signalling immune cells people multiple sclerosis innate immune response bacterial viral molecules involves coordinated production cytokines chemokines type interferons ifns orchestrated tolllike receptors tlrs tlrs intracellular signalling intermediates closely associated multiple sclerosis ms pathogenesis recent data laboratory reported plantderived cannabinoids tetrahydrocannabinol thc cannabidiol cbd regulate viral bacterial inflammatory,0.0
disrupted structural network inferomedial temporal regions relapsingremitting multiple sclerosis compared neuromyelitis optica spectrum disorder multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd two representative chronic inflammatory demyelinating disorders central nervous system aimed determine compare alterations white matter wm connectivity ms nmosd healthy controls hc study included 68 patients relapsingremitting ms 50 nmosd 26 hc networkbased statistics method used assess disrupted patterns wm networks topological,1.0
prevalence severity potential drugdrug interactions patients multiple sclerosis without polypharmacy polypharmacy pp common problem modern medicine especially known affect patients chronic diseases multiple sclerosis ms increasing number drugs taken risk potential drugdrug interactions pddis rising study aims assess prevalence clinical relevance polypharmacy pddis patients ms pharmacological data 627 patients ms entered two drugdruginteraction databases determine number,0.0
endocannabinoid modulation neurodegenerative diseases pursuit certainty neurodegenerative diseases increasing cause global morbidity mortality occur central nervous system cns lead functional mental impairment due loss neurons recent evidence highlights link neurodegenerative inflammatory diseases cns typically associated several neurological disorders diseases fundamental differences regarding underlying physiology clinical manifestations although,0.0
assessment factors associated depression anxiety among pwms saudi arabia background multiple sclerosis ms inflammatory chronic disease characterized increased prevalence adverse mental health outcomes patients ms pwms main aim study investigate factors depression anxiety pwms kingdom saudi arabia ksa materials methods crosssectional study conducted ksa period march june 2020 participants recruited neuroimmunology clinics king fahad medical city kfmc king saud university medical city ksumc riyadh city ksa hospital anxiety depression scale hads used measure depression anxiety fatigue severity scale fss used measure fatigue pwms simple random sampling technique utilized select participants data analyzed using spss v240 results total 529 participants participated study response rate 531 prevalences anxiety depression 353 197 respectively findings also revealed depression likely significantly affected male low education unemployment physical inactivity fatigue anxiety significantly affected region unemployment short duration since last ms relapse physical inactivity fatigue conclusion anxiety depression uncommon pwms given impact lives affected patients early detection management symptoms associated factors crucial keywords anxiety depression fatigue ksa multiple sclerosis,0.0
nfb signaling inflammationdrug repurposing treat inflammatory disorders nfb central mediator inflammation response dna damage oxidative stress result central role many important cellular processes nfb dysregulation implicated pathology important human diseases nfb activation causes inappropriate inflammatory responses diseases including rheumatoid arthritis ra multiple sclerosis ms thus modulation nfb signaling widely investigated approach treat chronic inflammatory,0.0
kinesiophobia people multiple sclerosis relationship physical activity pain acceptance disease background objectives multiple sclerosis ms common chronic demyelinating disease factors reduce occurrence symptoms include physical activity pa however data indicate pa levels among people ms lower healthy peers cause may kinesiophobia aim study determine level kinesiophobia among people ms relationship age disease duration functional status pa degree acceptance,1.0
prescription trends diseasemodifying treatments multiple sclerosis iran past 30 years backgroundiran middle income country one places high rising prevalence multiple sclerosis ms regarding substantial economic burden reviewing trend prescribed disease modifying treatments dmts help studied dmt information nearly 14000 ms cases trends change 30 years improve health services patientsmethodsthe population base descriptiveanalytical crosssectional study consisted ms patients nationwide ms registry iran nmsri august 1 2021 registrars 15 provinces 24 cities 13 hospitals 8 ms associations 16 private offices 7 clinics entered dataresultsoverall 14316 cases enrolled majority 761 female youngest eldest patients 5 78 years old respectively diagnosis delay one year cases median 0 iqr 0 1 614 involved rrms generally platform injectables ifn beta glatiramer acetate used dmts 2010 seems introduction newer agents anticd20s oral dmts resulted decrease use former drugs since around 2015 unusual practices prominent using approved dmts ppms years administering high efficacy drugs like natalizumab cis results indicate remaining popularity first line injectable dmts female pediatric patientsdiscussionmean age sd onset study 29 88 near statistics asia oceania 28 07 concerns covid19 noticeable impact administering high efficacy drugs like rituximab fingolimod however male patients approach case may related aggressive disease course group possible explanation planning pregnancy female cases popularity platform injectable drugs pediatric ms may related favorable safety profile years another point group superiority rituximab highly efficient medications,0.0
humoral response booster dose antisarscov2 vaccine multiple sclerosis patients treated highefficacy therapies antisarscov2 mrna vaccines showed blunted antibody ab response people ms pwms high efficacy therapies suggesting need booster dose evaluated kinetics production antirbd immunoglobulins g igg vaccination cycle booster pwms receiving ocrelizumab fingolimod cladribine significant increase antirbd igg seroconversion observed booster respect vaccination cycle results obtained study will useful management pwms relation disease modifying therapy dmt future vaccination campaign,0.0
sleep disturbances degree disability quality life multiple sclerosis patients sleep disturbances pervasive patients multiple sclerosis ms incidence four times higher compared general population frequent primary sleep problems include insomnia restless leg syndrome sleeprelated movement disorders sleepdisordered breathing study aims assess relationships sleeping problems quality life qol ms patients crosssectional study conducted among 152 ms patients mean age 3627,0.0
analysis choroidal vascularity index multiple sclerosis patients without optic neuritis attack background evaluate choroidal structural changes multiple sclerosis ms patients without previous optic neuritis attacks methods forty eyes 20 ms patients without history 40 eyes 20 agematched healthy volunteers included study choroidal thickness ct measured three points subfoveal 1500 m nasal fovea 1500 m temporal fovea choroidal area ca luminal area la choroidal vascularity index cvi calculated using imagej results mean subfoveal nasal temporal ct decreased ms patients compared controls p0001 mean la 05720113 mm2 ms group 07290188 mm2 controls p0002 mean cvi decreased ms group 6938487 comparison controls 7341518 p0034 conclusion current study demonstrated significant anatomical alterations choroid eyes patients ms keywords binarization choroid choroidal vascularity index luminal area multiple sclerosis,0.0
awareness covid19 symptoms risk factors vaccinations patients multiple sclerosis multiple sclerosis ms common chronic autoimmune disease central nervous system affecting around 28 million people worldwide patients knowledge covid19 infection proper protective actions may reduce risk infection aim study assess knowledge patients ms sarscov2 covid19 illness relationship ms covid19 willingness vaccinated impact pandemic ms care original,0.0
cannabinoids therapeutic use clinical practice medical case reports suggest cannabinoids extracted cannabis sativa therapeutic effects however therapeutic employment limited due psychotropic effect major component 9tetrahydrocannabinol thc new scientific discoveries related endocannabinoid system including new receptors ligands mediators allowed development new therapeutic targets treatment several pathological disorders minimizing undesirable psychotropic,0.0
crosscountry adaptation psychological flexibility measure comprehensive assessment acceptance commitment therapy processes abstract purpose comprehensive assessment acceptance commitment therapy act processes compact 23item selfreport questionnaire assessing psychological flexibility overarching construct underpinning act framework conducted twophase project develop validated versions compact three languages phase 1crosscultural adaptation phase 2psychometric validation questionnaire use italy germany spain article focuses first phase methods translated culturally adapted compact three target languages following ispor tca task force guidelines process overseen translation panel three translators least two multiple sclerosis ms researchers lay person act experts clinicians research team country original compact developers debriefed new questionnaire versions via facetoface interviews minimum four adults general population gp four adults ms country results translationadaptation process went smoothly three countries items 7 italy 4 germany 6 spain revised feedback act experts cognitive debriefing showed compact deemed easy understand score target country gp ms adults conclusions italian german spanish versions compact semantic conceptual normative equivalence original scale good content validity findings informative researchers adapting compact selfreported outcome measures multiple languages cultures keywords compact cultural adaptation linguistic validation outcome measures psychological flexibility,0.0
dual role nasal microbiota neurological diseasesan unignorable risk factor potential therapy carrier recently comparative studies rapidly increased closer correlation microbiota neurological diseases however insights association microbiota neurological diseases still focus gutbrain axis ignore nasal microbiota form complex essential link nervous system via nosetobrain pathway suggesting role modulating immune system metabolic system nervous system development influence,0.0
emerging biomarkers multiple sclerosis blood csf focus neurofilaments therapeutic considerations introduction multiple sclerosis ms common immunemediated chronic neurodegenerative disease central nervous system cns affecting young people due permanent disability cognitive impairment enormous detrimental impact ms can exert patients healthrelated quality life great importance recognise time commence adequate treatment early stage currently used diseasemodifying therapies dmt aim reduce,0.0
radiologically isolated aquaporin4 antibody neuromyelitis optica spectrum disorder aquaporin4 antibody aqp4ab neuromyelitis optica spectrum disorder nmosd rare neuroinflammatory syndrome presenting predominantly optic neuritis transverse myelitis report case radiologically isolated longitudinally extensive optic neuritis asymptomatic 12yearold female positive serum aqp4ab resolution imaging changes immune therapy contrast patients radiologically isolated syndrome will never convert multiple,0.0
nucleotide pyrophosphatase phosphodiesterases npps including npp1 npp2 atx important drug targets patent review 20152020 introduction nucleoside triphosphate diphosphohydrolases ntpdases alkaline phosphatases aps ectonucleotide pyrophosphatases phosphodiesterases npps nucleotidases found cell surface promising therapeutic target range disorders including fibrosis tumour metastasis pruritus inflammation multiple sclerosis autoimmune diseases result therapeutic intervention including selective inhibitors npps required,0.0
bsde barycenter singlecell differential expression casecontrol studies motivation singlecell sequencing brings revolutionarily high resolution finding differentially expressed genes disentangling highly heterogeneous cell tissues yet analysis far mostly focused comparing different cell types individual singlecell sequencing becomes cheaper easier use increasing number datasets casecontrol studies becoming available call new methods identifying differential expressions,0.0
preanalytical stability serum biomarkers forneurological disease neurofilamentlight glial fibrillary acidic protein contactin1 conclusions overall serum biomarkers tested relatively unaffected variations sample handling serum nfl recommend storage rt centrifugation 28 c 6 h rt 24 h serum cntn1 advise maximum two freezethaw cycles results confirm expand recently launched consensus standardized operating procedures,0.0
bayesian network predict risk post influenza vaccination guillainbarr syndrome development validation study conclusions findings study illustrated bn model can effectively identify significant factors gbs improve understanding complex interactions among different postvaccination symptoms graphical representation accurately predict risk gbs established bn model assist clinical decisionmaking providing estimated risk gbs specific vaccinee developed openaccess platform vaccinees,0.0
innovating care multiple sclerosis feasibility synchronous internetbased teleconsultation longitudinal clinical monitoring coronavirus disease 2019 crisis recently forced expedited adoption teleconsultation tc medical domains shortterm digital interventions generally associated feasibility clinical benefits user satisfaction costeffectiveness patients multiple sclerosis ms outcomes repeated utilization extended periods need evaluated feasibility study 60 subjects ms 11 randomized receive standard care,0.0
entropy approach multiple sclerosis identification multiple sclerosis ms relatively common neurodegenerative illness frequently causes large level disability patients cause fully understood likely due combination genetic environmental factors diagnosis multiple sclerosis simple clinical examination might challenging evolution illness varies significantly patient patient patients experiencing long periods remission regard,0.0
structural plasticity hippocampus neurodegenerative diseases neuroplasticity capacity neural networks brain alter development rearrangement can classified structural functional plasticity hippocampus susceptible neuroplasticity compared brain regions structural modifications hippocampus underpin several neurodegenerative diseases exhibit cognitive emotional dysregulation article reviews findings several preclinical clinical studies role,0.0
sense coherence healthrelated quality life patients multiple sclerosis role physical neurological disability multiple sclerosis progressive demyelinating disease central nervous system can lead permanent disability significantly impact quality life present study explores relationship neurological disability disease symptoms quality life level sense coherence important resource coping disease edss gnds soc29 msis29 used presented study study group consisted 137 people diagnosed,1.0
cd8sup+ sup t cell senescence lights shadows viral infections autoimmune disorders cancer cd8 + t lymphocytes heterogeneous class cells play crucial role adaptive immune response pathogens cancer lifetime acquire cytotoxic functions ensure clearance infected transformed cells addition turn memory lymphocytes thus providing longterm protection ageing thymic involution causes reduction circulating t cells enrichment memory cells partially explaining lowering,0.0
emergency medical care multiple sclerosis fiveyear population study campania region south italy background emergency hospital admissions common multiple sclerosis ms can highlight unmet medical needs objectives evaluate burden predictors outcomes ms emergency admissions methods populationbased study conducted campania region south italy 2015 2019 using hospital discharge records drug prescriptions outpatients risk emergency hospital admissions likelihood worse outcomes evaluated using cox regression multinomial logistic regression models respectively relation age sex diseasemodifying treatments dmts comorbidities adherence results recorded 1225 emergency admissions 1001 patients 5765 prevalent ms patients overall costing 4 143 76467 eur risk emergency admissions increased age hazard ratio hr 102 95 confidence interval ci 101 103 p 001 comorbidities hr 162 p 001 decreased patients using dmts interferon beta peginterferon beta glatiramer acetate hr 019 p 001 teriflunomide dimethylfumarate fingolimod hr 018 p 001 alemtuzumab cladribine natalizumab ocrelizumab hr 021 p 001 higher adherence hr 018 95 ci 013 026 p 001 following emergency admission older age associated probability death n 63 odds ratio 106 p 001 discharge longterm facility n 65 103 p 001 conclusion 17 people ms requiring emergency medical care 5 years improved management dmts comorbidities potentially reduce medical social financial burden keywords multiple sclerosis adherence cost death emergency treatment,0.0
emerging insights complex genetics pathophysiology amyotrophic lateral sclerosis amyotrophic lateral sclerosis fatal neurodegenerative disease discovery genes associated amyotrophic lateral sclerosis commencing sod1 1993 started fairly gradually recent advances genetic technology led rapid identification multiple new genes associated disease new understanding oligogenic polygenic disease risk overlap genes associated amyotrophic lateral sclerosis neurodegenerative,0.0
psychological benefits neuropsychological assessment feedback psychoeducational therapeutic intervention randomizedcontrolled trial crossover multiple sclerosis abstractevidence supporting direct therapeutic benefits neuropsychological assessment npa feedback relies mostly upon postfeedback consumer surveys randomizedcontrolled trial crossover investigated benefits npa feedback multiple sclerosis ms seventyone participants randomly allocated npa feedback delayedtreatment control group primary hypotheses npa feedback lead improved knowledge cognitive functioning,0.0
high levels cerebrospinal fluid kappa free light chains relate igm intrathecal synthesis might prognostic implications relapsing multiple sclerosis cerebrospinal kappa free light chain kflc index marker intrathecal immunoglobulin synthesis aids diagnosis multiple sclerosis ms however little evidence exists prognostic role aim analyze relationship kflcindex ms biomarkers explore prognostic role monocentric observational study cohort 52 people relapsing ms pwrms performed prospectively acquired clinical data retrospective,0.0
phase 1 evaluation sup11 supccs1p1 assess safety dosimetry human participants purpose study evaluated safety dosimetry characteristics 11 ccs1p1 radiotracer targeting sphingosine1phoshate receptor 1 sphingosine1phoshate receptor 1 clinical interest role multiple sclerosis conditions expanding class sphingosine1phosphate receptor modulators approved relapsing multiple sclerosis 11 ccs1p1 binds sphingosine1phosphate receptor 1 high specificity shown promise animal models,0.0
mri predictors conversion contrastenhancing iron rim multiple sclerosis lesions background multiple sclerosis ms iron rim lesions irls characterized progressive tissue matrix damage therefore early identification represent interesting target therapeutic intervention minimize evolving tissue damage aim study identify magnetic resonance imaging mri parameters predicting conversion contrastenhancing irls,0.0
optical coherence tomography neurodegenerative disorders abstract structural imaging brain widely used diagnostic tool investigating neurodegenerative diseases advanced structural imaging techniques applied early prodromic phases expensive widely available therefore highly desirable search noninvasive easily accessible lowcost clinical biomarkers suitable largescale population screening order focus making diagnoses earliest stages disease scenario imaging studies focusing structures retina increasingly used evaluating neurodegenerative diseases retina shares embryological histological biochemical microvascular neurotransmitter similarities cerebral cortex thus making uniquely promising biomarker neurodegenerative diseases optical coherence tomography modern noninvasive imaging technique provides highresolution twodimensional crosssectional images quantitative reproducible threedimensional volumetric measurements optic nerve head retina technology widely used ophthalmology practice diagnosing following several eye diseases glaucoma diabetic retinopathy agerelated macular degeneration clinical impact neurodegenerative diseases raised enormous interest recent years several clinical studies demonstrated diseases give rise reduced thickness inner retinal nerve fiber layer mainly composed retinal ganglion cells axons review aimed address clinical utility optical coherence tomography diagnosing evaluating different neurodegenerative diseases show potential noninvasive easily accessible method,0.0
psychological impact covid19 pandemic people multiple sclerosis metaanalysis background covid19 pandemic caused relevant psychological consequences general population since people multiple sclerosis pwms usually higher risk psychological distress agematched healthy controls hc metaanalytic study conducted aimed evaluating differences pwms hc psychological variables pandemic ii differences levels anxiety depression stress sleep disturbances quality life covid19 pandemic pwmsmethods literature search three electronic databases yielded 196 studies 113 duplicates removal seven studies compared psychological variables pwms hc pandemic seven studies evaluated pre vs pandemic differences pwms following outcomes selected depression anxiety physical qol mental qol stress sleep quality disturbances mean weighted effect sizes es calculated using hedgesg via prometa3 softwareresults pandemic pwms showed higher levels depression g051 p0001 anxiety g041 p0032 stress g051 p0016 compared hc comparison psychological outcomes pandemic pwms revealed significant increase pandemic levels anxiety g008 p0380 depression g002 p0772 mental qol g 014 p0060 physical qol g000 p0986 whereas sleep quality deteriorated pandemic g052 p0001 conclusions agreement prepandemic literature pwms showed higher levels psychological distress hc also covid19 pandemic contrariwise longitudinal studies revealed pwms psychologicalassociated variable worsened significantly sleep quality outcome evaluated two studies future studies will assess evaluate longterm psychological consequences pandemic pwms,0.0
hearing loss among patients multiple sclerosis pwms systematic review metaanalysis backgroundmultiple sclerosis ms kind autoimmune disorder swept 2 million people worldwide caused multiple disabilities patients hearing loss hl also one disabilities numerous patients multiple sclerosis pwms experiencemethodswe searched four databases pubmed medline scopus web science embase 1970 july 2021 gray literature containing conference abstracts review studies references articles also investigated included studies reported pwms hlresultsout 1875 articles 1042 articles remained following eliminating duplicates afterward articles screened 953 eliminated based exclusion criteria full texts 89 articles collected finally eight articles selected based inclusion exclusion pooled prevalence hl pwms 11 95 ci 02 24 i28011 p0001 among 5187 ms populationconclusionour analysis suggests ms might risk hl patients might indicator ms diagnosis research larger sample numbers forms hl required,0.0
psychological impact covid19 pandemic people multiple sclerosis metaanalysis abstractbackgroundcovid19 pandemic caused relevant psychological consequences general population since people multiple sclerosis pwms usually higher risk psychological distress agematched healthy controls hc metaanalytic study conducted aimed evaluating differences pwms hc psychological variables pandemic ii differences levels anxiety depression stress sleep disturbances quality life covid19 pandemic pwmsmethodsthe literature search three electronic databases yielded 196 studies 113 duplicates removal seven studies compared psychological variables pwms hc pandemic seven studies evaluated pre vs pandemic differences pwms following outcomes selected depression anxiety physical qol mental qol stress sleep quality disturbances mean weighted effect sizes es calculated using hedgesg via prometa3 softwareresultsduring pandemic pwms showed higher levels depression g051 p001 anxiety g041 p032 stress g051 p016 compared hc comparison psychological outcomes pandemic pwms revealed significant increase pandemic levels anxiety g008 p380 depression g002 p772 mental qol g 014 p060 physical qol g000 p986 whereas sleep quality deteriorated pandemic g052 p001 conclusionsin agreement prepandemic literature pwms showed higher levels psychological distress hc also covid19 pandemic contrariwise longitudinal studies revealed pwms psychologicalassociated variable worsened significantly sleep quality outcome evaluated two studies future studies will assess evaluate longterm psychological consequences pandemic pwms,0.0
predictors unemployment status people relapsing multiple sclerosis single center experience background multiple sclerosis ms common cause nontraumatic chronic neurological disability affecting young adults crucial employment years objectives evaluate patients disease related factors associated unemployment cohort relapsingremitting rr ms patients methods included rrms patients followup least 1 year collected data years school education employment status patients underwent neuropsychological evaluation using brief international cognitive assessment multiple sclerosis bicams demographic clinical predictors unemployment assessed multivariable stepwise logistic regression model results evaluated 260 consecutive rrms patients employed patients less frequently female 684 vs 833 p 0006 less disabled median expanded disability status scale edss score 20 070 vs 25 075 p 0001 years school education mean standard deviation sd years 1374 030 vs 1086 347 p 0001 female sex higher edss score resulted associated greater risk unemployment 3510 95 ci 16547448 p 0001 1366 95 ci 10741737 p 0011 respectively whereas greater number years schooling current diseasemodifying therapy exposure resulted protective factors 0788 95 ci 07230858 p 0 001 0414 95 ci 02170790 p 0008 respectively conclusions understanding work pervasively influenced consequences ms confirmed impact demographic physical cognitive factors employment status rrms patients keywords disabilty multiple sclerosis unemployment,0.0
designing multiarm multistage adaptive trials neuroprotection progressive multiple sclerosis progressive multiple sclerosis pms significant health problem treatments shown slow disability progression one challenge efficiently testing pipeline candidate therapies preclinical studies clinical trials multiarm multistage mams platform trials may accelerate evaluation new therapies compared traditional sequential clinical trials describe mams design pms focusing selection interim final outcome measures sample size,0.0
keeping together role social integration health psychological wellbeing among individuals multiple sclerosis research indicates people multiple sclerosis ms likely report poorer health wellbeing peers without ms fortunately also known individuals social lifestyle factors play great role maintaining promoting ones health overall wellbeing present study aimed examine role social integration social support particular health psychological wellbeing pwb among individuals ms one hundred,0.0
pharmacologically enhanced regulatory hematopoietic stem cells revert experimental autoimmune diabetes mitigate autoimmune disorders type 1 diabetes t1d characterized loss immune selftolerance resulting aberrant immune responses selftissue therapeutics partially successful reverting slowing t1d progression patients infusion autologous hematopoietic stem cells hscs emerging option explored study proposed pharmacologically enhance ex vivo modulation small molecules immunoregulatory trafficking properties,0.0
dysregulation translation tdp43 proteinopathies deficits rna supply chain local protein production local control gene expression provides critical mechanisms regulating development maintenance plasticity nervous system among strategies known govern gene expression locally mrna transport translation emerged essential neurons ability navigate developmental cues establish strengthen remove synaptic connections throughout lifespan substantiating role rna processing nervous system several rna binding proteins,0.0
effects nonsurgical minimally noninvasive therapies urinary incontinence due neurogenic bladder systematic review metaanalysis abstract objective determine effects nonsurgical minimally noninvasive therapies urge urinary incontinence uui symptoms quality life qol individuals neurogenic bladder ngb data sources cochrane library embase medline pedro scopus web science databases searched inception september 2021 review methods randomized controlled trials compared therapies intravaginal electrical stimulation ives transcutaneous electrical nerve stimulation tens neuromuscular electrical stimulation nmes transcutaneous tibial nerve stimulation ttns pelvic floor muscle training pfmt behavioural therapy bt control included study screening data extraction study quality assessments performed two independent authors results fourteen trials 804 participants included study screening 4281 potentially relevant articles metaanalyses revealed significant effect electrical stimulation uui due multiple sclerosis standardized mean difference smd 0614 95 confidence interval ci 1023 0206 p 0003 stroke smd 2639 95 ci 3804 1474 p 0000 pooled analyses ttns weighted mean difference wmd 12406 95 ci 16015 8797 p 0000 bt wmd 9117 95 ci 14746 3487 p 0002 revealed significant effects interventions qol people parkinsons disease however metaanalyses revealed nonsignificant effects pfmt wmd 0751 95 ci 2426 0924 p 0380 bt wmd 0597 95 ci 1278 0083 p 0085 uui due parkinsons disease conclusions metaanalyses found electrical stimulation beneficial improving symptoms uui among people multiple sclerosis stroke review also revealed ttns bt might improve qol people ngb due parkinsons disease although effects pfmt bt uui warrant investigation keywords neurogenic bladder systematic review metaanalysis therapies urinary incontinence,0.0
preclinical analysis candidate antihuman cd79 therapeutic antibodies using humanized cd79 mouse model bcr comprises membranebound ig noncovalently associated heterodimer cd79a cd79b bcr ig component functions sense extracellular ag cd79 subunits contain cytoplasmic itams mediate intracellular propagation bcr signals critical b cell development survival aginduced activation cd79 therefore attractive target ab chimeric ag receptor t cell therapies autoimmunity b cell neoplasia although mouse attractive,0.0
synergistic enhancement rat intestinal alkaline phosphatase activity taurine sodium butyrate protects endotoxininduced bowel inflammation effect sodium butyrate sb taurine rat intestinal alkaline phosphatase ria effect interaction taurine sb bacterial lipopolysaccharides alp activity investigated vitro analysis activity ria carried using various concentrations sb taurine substrate concentrationdependent kinetic study performed 110 mm taurine sb 517 mm pnitrophenyl phosphate pnpp vivo effect,0.0
thinking anew accelerating clinical trials new therapies progressive multiple sclerosis abstract,1.0
bone fragility chronic kidney disease stage 3 5 use vitamin d supplementation frequently silent advanced stages bone fragility associated chronic kidney diseasemineral bone disease ckdmbd one devastating complications ckd pathophysiology includes reduction active vitamin d metabolites phosphate accumulation decreased intestinal calcium absorption renal alpha klotho production elevated fibroblast growth factor 23 fgf23 levels altogether factors contribute firstly secondary hyperparathyroidism,0.0
elevated atp via enhanced mirna30b 30c 30e downregulates expression cd73 cd8+ t cells hivinfected individuals cd8+ t cells play crucial role chronic viral infections however effector functions influenced expression costimulatory inhibitory receptors example cd73 works cd39 convert highly inflammatory atp adenosine however expression t cells context viral infections well defined analyzed expression cd73 human t cells cohort 102 hivinfected individuals including antiretroviral therapy,0.0
genetically engineered mesenchymal stem cell therapy murine experimental autoimmune encephalomyelitis used recombinant interleukin 23 receptor ril23r engineered mesenchymal stem cells mscs study therapeutic role enhancing inflammation nervous tissue mouse model eae multiple sclerosis ms recombinant il23 receptor construct designed enter mscs bioactivity constructs assessed coculture mscs cd4 + t cells eae model induced mice cell transplantation clinical scores evaluated tissue demyelination,1.0
tsubh sub cells cytokines encephalitogenic disorders invasion immune cells central nervous system cns hallmark process call neuroinflammation diseases encephalitides multiple sclerosis ms characterised dramatic influx t lymphocytes monocytes communication inflammatory infiltrates cns resident cells primarily mediated cytokines years numerous cytokine networks assessed better understand development immunopathology,0.0
association cerebrospinal fluid parameters neurofilament light chain retinal nerve fiber layer thickness multiple sclerosis abstract introduction multiple sclerosis ms pathophysiology comprises inflammatory neurodegenerative characteristics cerebrospinal fluid csf analysis allows assessment inflammation neurofilament light chain can indicate neuroaxonal damage retinal thinning robust prognostic biomarker neurodegeneration ms date association csf parameters upon ms diagnosis retinal thinning investigated aims objectives aimed determine whether csf parameters associated evolution retinal layer thinning people ms pwms methods longitudinal observational study investigated pwms vienna ms database vmsd undergone 1 diagnostic lumbar puncture lp 2015 2020 2 simultaneous optical coherence tomography oct 3 followup oct scan linear stepwise regression models calculated oct parameters peripapillary retinal nerve fiber layer prnfl thickness lp followup annualized loss prnfl thickness alprnfl dependent variable csf parameters white blood cell wbc count total protein csftp csf serum albumin ratio qalb intrathecal synthesis immunoglobulins neurofilament light chain nfl csf serum csfnfl snfl independent variables adjusted age sex disease duration results analyzed 61 pwms median age 300 years interquartile range 255350 574 female median disease duration 10 month iqr 020 lp median followup 19 years iqr 1135 csfnfl snfl measurements available 26 31 pwms respectively prnfl thickness lp inversely associated csf wbc count 036 95 ci 051 008 p 0008 find association csf parameters including csfnfl snfl alprnfl conclusions increased wbc count indicator acute inflammation bloodbrainbarrier breakdown seems associated amount retinal thickness already lost time lp however neither routine csf parameters singular nfl measurement allows prediction future retinal thinning keywords rnfl biomarker cerebrospinal fluid multiple sclerosis neurofilament optical coherence tomography,0.0
predictors correlates emotionalism across acquired progressive neurological conditions systematic review emotionalism can develop following range neurological disorders however aetiology emotionalism still unclear identify anatomical neuropsychological psychological predictors correlates emotionalism across neurological disorders stroke parkinsons disease multiple sclerosis traumatic brain injury alzheimers disease vascular dementia amyotrophic lateral sclerosis explore predictors correlates emotionalism differ across neurological,0.0
biochanin improves memory decline brain pathology cuprizoneinduced mouse model multiple sclerosis multiple sclerosis ms chronic inflammatory neurodegenerative disease central nervous system characterized demyelination nerves neural degeneration axonal loss cognitive impairment including memory decline significant feature ms affecting 70 patients thereby substantially impacts patients quality life biochanin bca omethylated isoflavone wide variety pharmacological activities including antioxidant,1.0
mediating role stigma internalized shame autonomous motivation relationship depression anxiety psychological helpseeking attitudes multiple sclerosis background depression anxiety commonly experienced individuals multiple sclerosis ms yet little known factors associated psychological helpseeking attitudes ms method current study investigated whether increased stigma related chronic illness internalized shame autonomous motivation mediated relationship depressive anxiety symptoms psychological helpseeking attitudes individuals ms two hundred fiftyfour participants ms completed online questionnaire assessing depressive anxiety symptoms stigma related chronic illness internalized shame autonomous motivation psychological helpseeking attitudes results stigma related chronic illness internalized shame autonomous motivation mediated relationships increased depressive symptoms anxiety symptoms psychological helpseeking attitudes study also found higher levels chronic illnessrelated stigma internalized shame associated negative psychological helpseeking attitudes higher autonomous motivation associated positive psychological helpseeking attitudes direct effects depressive anxiety symptoms psychological helpseeking attitudes conclusion significant mediating roles stigmarelated chronic illness internalized shame autonomous motivation indicate factors may useful include future depression anxiety intervention studies targeting ms populations keywords anxiety autonomous motivation depression multiple sclerosis psychological helpseeking attitudes shame stigma,0.0
reactivity rheumatoid arthritisassociated citrullinedependent antibodies epsteinbarr virus nuclear antigen13 rheumatoid arthritis ra chronic disease causes joint inflammation ultimately erosion underlying bone diagnosis ra based presence biomarkers anticitrullinated protein antibodies acpa rheumatoid factors along clinical symptoms much evidence points link epsteinbarr virus ra study analyzed acpa reactivity citrullinated peptides originating epsteinbarr nuclear antigens ebna1 ebna2,0.0
priming postural training cerebellar anodal transcranial direct current stimulation effects postural balance fear falling patients multiple sclerosis randomized doubleblind shamcontrolled study postural impairment one disorders patients multiple sclerosis ms fear falling can exacerbate patients one leading causes postural impairment fear falling patients ms cerebellum regions abnormalities may modulated cerebellar anodal transcranial direct current stimulation atdcs present study aimed investigate effects cerebellar atdcs concurrent postural training cerebellar,0.0
optical control protein delivery partitioning nucleolus nucleolus subnuclear membraneless compartment intimately involved ribosomal rna synthesis ribosome biogenesis stress response multiple optogenetic devices developed manipulate nuclear protein import export molecular tools tailored remote control selective targeting partitioning cargo proteins subnuclear compartments capable phase separation still limited report set singlecomponent photoinducible,0.0
progression independent relapse activity early multiple sclerosis reallife cohort study disability accrual multiple sclerosis may occur relapseassociated worsening progression independent relapse activity role progression independent relapse activity early ms yet established objective multicentre observational retrospective cohort study investigate contribution relapseassociated worsening progression independent relapse activity confirmed disability accumulation patients clinically isolated syndrome,0.0
botulinum toxin essential tremor hands tremor neurological diseases metaanalysis randomized controlled trials tremor common movement disorder essential tremor et common etiology tremor hands tremor disabling type tremor study aimed explore effects botulinum toxin bont tremor within 6 weeks treatment muscular weakness adverse effect within 6 weeks specifically randomized controlled trials pubmed embase cochrane library databases searched tremor severity grip strength bont treatment investigated,0.0
antisarscov2 vaccination time covid19 pandemic suspected adverse events reporting milestone postmarketing surveillance abstract,0.0
3dimensional fluid white matter suppression magnetic resonance imaging sequence accelerated compressed sensing improves multiple sclerosis cervical spinal cord lesion detection compared standard 2dimensional imaging abstract objectives fluid white matter suppression flaws recently proposed magnetic resonance sequence derived magnetizationprepared 2 rapid acquisition gradientecho providing 2 coregistered datasets white matter cerebrospinal fluidsuppressed signal enabling synthetic imaging amplified contrast although features high potential brain multiple sclerosis ms imaging spinal cord never evaluated sequence date objective work therefore assess diagnostic performance selfconfidence provided compressedsensing cs 3dimensional 3d flaws cervical ms lesion detection head scan includes cervical cord without changing standard procedures materials methods prospective 3 t scans ms first diagnosis followup acquired 2019 2020 retrospectively analyzed patients underwent 3d csflaws duration 5 minutes 40 seconds axial t2 turbo spin echo covering cervical spine cervicomedullary junction inferior level flaws sagittal cervical t2 short tau inversion recovery imaging two readers performed 2stage doubleblind reading followed consensus reading wilcoxon tests used compare number detected spinal cord lesions readers diagnostic selfconfidence using flaws versus reference 2d t2weighted imaging results fiftyeight patients included mean age 40 13 years 46 women 7 6 years mean disease duration csflaws detected significantly lesions reference t2weighted imaging 197 vs 152 detected lesions p 0001 sensitivity 98 t2weighted imaging sensitivity 90 consensual reading considering subgroup patients underwent sagittal t2 + short tau inversion recovery imaging magnetic resonance imaging multiple sclerosis subgroup +250 lesions detected flaws 63 vs 25 lesions detected p 0001 mean reading selfconfidence significantly better csflaws median 5 interquartile range 1 doubt diagnosis vs 4 interquartile range 1 high confidence p 0001 conclusions imaging csflaws provides improved cervical spinal cord exploration ms increased selfconfidence compared conventional t2weighted imaging clinically acceptable time,0.0
sixminute walk performance related factors pediatriconset multiple sclerosis abstract objective investigate functional exercise capacity relationship physical activity levels muscle strength balance fatigue quality life patients pediatriconset multiple sclerosis methods fifteen patients pediatriconset multiple sclerosis included 6minute walk test used determine functional exercise capacity walking distance godin leisuretime exercise questionnaire pedometer used evaluate physical activity timedup go dynamic balance isokinetic testing lower extremity muscle strength fatigue severity scale fatigue pediatric quality life inventory pedsql quality life results 6minute walking distance positively correlated glteq schoolwork subgroup score pedsqlselfreport negatively correlated timedup go fatigue severity scale dynamic balance physical activity fatigue significant predictors 6minute walking distance conclusions results showed 6minute walk test influenced physical activity dynamic balance fatigue related quality life patients pediatriconset multiple sclerosis keywords balance functional exercise capacity pediatriconset multiple sclerosis physical activity sixminute walk test,0.0
cladribine tablets relapsingremitting multiple sclerosis clinicians review multiple sclerosis ms chronic neurodegenerative disease characterized inflammation demyelination currently cure therefore aim therapy reduce risk relapse disability progression treatment options ms increased greatly recent years development several diseasemodifying therapies dmts advent immune reconstitution therapy irt irts administered shortdosing periods produce longterm,1.0
pregnancy planning health information service needs women chronic noncommunicable conditions systematic review narrative synthesis conclusion improve pregnancy outcomes women living ncds health care providers need ask women reproductive age proactively routinely pregnancy intentions provide personalised advice avoid unplanned pregnancy optimal health wish conceive prospero registration number crd42020176308,0.0
blue rubber bleb nevus syndrome pakistani child case report regional literature review blue rubber bleb nevus syndrome brbns rare disorder development multiple venous malformations haemangiomas skin visceral organs lesions mostly involve skin gastrointestinal systems organs including liver muscles central nervous system can also involved untreated affected individuals develop severe anaemia cases managed iron supplementation blood transfusions may require surgical,0.0
nr1d1 downregulation astrocytes induces phenotype detrimental cocultured motor neurons nuclear receptor subfamily 1 group d member 1 nr1d1 also known reverb nuclear transcription factor part molecular clock encoding circadian rhythms may link daily rhythms metabolism inflammation nr1d1 unlike nuclear receptors lacks liganddependent activation function domain 2 constitutive transcriptional repressor amyotrophic lateral sclerosis als common adultonset motor neuron disease caused progressive,0.0
natural polysaccharides alleviate neurological disorders new updates due difficulty pathogenesis nervous system disease nsd therapies long challenging problems researchers rise ageing population quest successful nsd therapies become hot topic polysaccharides demonstrated numerous biological effects antioxidation antiinflammation immune regulationin recent years several studies conducted light connection properties polysaccharides pathogenesis,0.0
targeted medical history diagnostic testing uveitis uveitis collective term variety different intraocular inflammations underlying etiologies vary greatly depending uveitis subtype particular anatomical focus common forms anterior uveitis acute fibrinous unilateral uveitis often associated hlab27 haplotype granulomatous inflammation typically associated sarcoidosis herpes infections intermediate uveitis usually idiopathic nature can also associated,0.0
effect fermented foods neurological diseases microbiota behaviors mini review fermented foods among traditional foods consumed centuries recent years awareness fermented foods increasing due positive health benefits fermented foods contain beneficial microorganisms fermented foods kefir kimchi sauerkraut yoghurt contain lactic acid bacteria lab lactobacilli bifidobacteria primary metabolites lactic acid although studies effect consumption fermented foods diabetes,0.0
different prognostic patterns epilepsies considerations denotations atypical patterns epilepsy dynamic heterogeneous neurological disease longterm studies prognosis classically 5 basic patterns early remission late remission relapsingremitting worsening nonremitting identified frequent pattern relapsingremitting course factors presence genetic etiology rare seizures beginning epilepsy absence psychiatric comorbid diseases found related pattern well,0.0
decision making process multiple sclerosis argentine pilot study backgroundthere scarce information regarding decisionmaking process dmp people ms pwms latin americaobjectiveto evaluate dmp argentinean pwms assess relationship patient preferences clinicaldemographic characteristicsmethodspwms patient organization esclerosis mltiple argentina n 1275 invited participate selfadministered webbased survey participants asked provide clinicaldemographic information complete questionnaire perceptions information provided physician control preference scale satisfaction decisions care questionnaire inquired preferred sources information msresultsthe survey completed 379 pwms females 67 mean age 403 sd111 years mean disease duration 79 sd 72 years patients decisional control preferred role active 47 shared 27 passive 26 moderate concordance weighted kappa 055 observed patients preferences selfreported dmp seventytwo percent participated dmp according preferences concordance rates active 66 shared 87 passive 51 83 declared receiving information neurologists matching preferences 94 conclusionsargentinian pwms distinctive preferences regarding information management decision making,0.0
agenda global patient reported outcomes multiple sclerosis proms initiative progresses open questions abstracton 12 september 2019 global patient reported outcome multiple sclerosis proms initiative launched 35th congress european committee treatment research multiple sclerosis ectrims multistakeholder proms initiative jointly led european charcot foundation ecf multiple sclerosis international federation msif italian ms society aism acting lead agency behalf global msif movement initiative ambitious mission maximize impact science patient input life people affected ms ii represent unified view patientreported outcomes ms people affected ms healthcare providers regulatory agencies health technologies assessments agencies equipped innovative participatory governance international interdisciplinary network different stakeholders proms potential guide future breakthroughs ms patientfocused research care paper present progresses global proms initiative discuss open questions aim address,0.0
influence socioeconomic factors access disease modifying treatment norwegian multiple sclerosis cohort objectiveseveral studies report impact socioeconomic factors access disease modifying treatment dmt multiple sclerosis ms trend less access deprived persons investigated impact socioeconomic status ses access treatment welldefined norwegian ms cohortmethodsthis study populationbased norwegian ms cohort collected detailed information disease development progression dmt administered socioeconomic data obtained statistics norway questionnaireresultswe included 1314 persons relapsing remitting ms prevalence date 01 01 2018 population ever treated dmts younger onset shorter time onset diagnosis lower expanded disability status score edss diagnosis persons ms pwms highest levels education married likely ever treated dmt subgroup treated high efficacy dmt first drug pwms younger prevalence date 399 years sd 121 compared treated high efficacy dmt first drug 438 years sd 103 subgroup treated high efficacy dmt first drug 05 point higher edss diagnosis compared treated high efficacy dmt first drug level education household income marital status inversely related access high efficacy dmt first drug none differences persist analyzing subgroup diagnosed within last six years 20122017 conclusionssince 2012 pwms norwegian cohort treated equally dmt terms different measures socioeconomic position,0.0
progressive retinal changes pediatric multiple sclerosis objectives determine extent acute demyelinating episodes versus chronic degenerative phenomena drive retinal neuroaxonal damage pediatric acquired demyelinating syndromes ads methods acquired optical coherence tomography oct data followup range 2 weeks 5 years variable intervals presentation pediatric participants multiple sclerosis ms monophasic ads healthy multivariable mixed effects models used assess association number demyelinating episodes either optic neuritis nonon relapses changes retinal nerve fiber layer rnfl ganglion cell layerinner plexiform layer gcipl thicknessresults 64 oct sans 23 ms 33 scans 12 monophasic ads participants compared 68 scans 62 healthy participants first episode biggest impact rnfl gcipl thickness monophasic ads rnfl 79 m ci55 p 00056 gcipl 84 m ci44 p 00002 ms rnfl 16 m ci 37 p 106 gcipl 15 m ci 26 p 106 nonon relapses also associated small significant retinal thickness reductions ms rnfl 26 m relapse ci 14 p 00003 gcipl 28 m relapse ci 089 p 106 ms participants showed progressive gcipl thinning independent acute demyelinating episodes 27 m year ci 19 p 00058 conclusions showed prominent impact early episodes oct measures neuroaxonal structure patients ads also demonstrated negative effects nonon relapses presence chronic retinal neurodegenerative changes youth ms,1.0
decision making process multiple sclerosis argentine pilot study abstractbackgroundthere scarce information regarding decisionmaking process dmp people ms pwms latin americaobjectiveto evaluate dmp argentinean pwms assess relationship patient preferences clinicaldemographic characteristicsmethodspwms patient organization esclerosis mltiple argentina n1275 invited participate selfadministered webbased survey participants asked provide clinicaldemographic information complete questionnaire perceptions information provided physician control preference scale satisfaction decisions care questionnaire inquired preferred sources information msresultsthe survey completed 379 pwms females 67 mean age 403 sd111 years mean disease duration 79 sd72 years patients decisional control preferred role active 47 shared 27 passive 26 moderate concordance weighted kappa 055 observed patients preferences selfreported dmp seventytwo percent participated dmp according preferences concordance rates active 66 shared 87 passive 51 83 declared receiving information neurologists matching preferences 94 conclusionsargentinian pwms distinctive preferences regarding information management decision making,0.0
agenda global patient reported outcomes multiple sclerosis proms initiative progresses open questions abstracton 12 september 2019 global patient reported outcome multiple sclerosis proms initiative launched 35th congress european committee treatment research multiple sclerosis ectrims multistakeholder proms initiative jointly led european charcot foundation ecf multiple sclerosis international federation msif italian multiple sclerosis society aism acting lead agency behalf global msif movement initiative ambitious mission maximize impact science patient input life people affected ms ii represent unified view patientreported outcomes ms people affected ms healthcare providers regulatory agencies health technologies assessments agencies equipped innovative participatory governance international interdisciplinary network different stakeholders proms potential guide future breakthroughs ms patientfocused research care paper present progresses global proms initiative discuss open questions aim address,0.0
prognostic biomarkers primary progressive multiple sclerosis validating scrutinizing multimodal evoked potentials abstract objective validate prognostic value multimodal evoked potentials mmep primary progressive multiple sclerosis ppms determine predictive epmodalities methods thirtynine patients ppms expanded disability status scale edss 2065 mean clinical followup 28 years visual vep upper lower limb somatosensory sep motor ep mep baseline quantitative epscores single qvep qsep qmep combined modalities correlated edss compared previously published data 21 ppms patients predictors edsschange analyzed pooled data linear regression results samples comparable except qvep epscores correlated edss baseline rho 045069 p 001 followup rho 059080 p 0001 combined epmodalities significantly predicted edsschange r2adj 024 edss age tibial qsep r2adj 022 qmep r2adj 026 best single modality predictors outperformed combination r2adj 032 conclusions quantitative epscores predict 32 edsschange three years modalities representing motor long tract function carry main prognostic information significance replication previous results corroborates use mmep prognostic biomarker candidate ppms keywords biomarker clinical trial design evoked potentials prognosis progressive multiple sclerosis quantitative ep score,0.0
simultaneous assessment regional distributions atrophy across neuraxis ms patients background ability assess brain cord atrophy simultaneously improve efficiency mri track disease evolution objective test promising tool simultaneously map regional distribution atrophy multiple sclerosis ms patients across brain cord methods voxelbased morphometry combined statistical parametric mapping probabilistic brainspinal cord spmbsc template applied standard t1weighted magnetic resonance imaging mri scans covering brain cervical cord 37 ms patients 20 healthy controls hc also measured cord area c2c3 semiautomatic segmentation method using t1weighted acquisitions used new voxelbased analysis ii dedicated spinal cord phase sensitive inversion recovery psir acquisitions cervical cord findings derived three approaches compared goodness fit clinical scores assessed regression analyses results spmbsc approach revealed severitydependent pattern atrophy across cervical cord thalamus ms patients compared hcs magnitude cord atrophy confirmed semiautomatic extraction approach c2c3 using standard brain t1weighted advanced cord dedicated acquisitions associations atrophy cord thalamus disability cognition demonstrated conclusion atrophy brain cervical cord ms patients can identified simultaneously rapidly voxellevel spmbsc approach yields similar results available standard processing tools added advantage performing analysis simultaneously faster,0.0
innate immune receptor nlrp12 suppresses autoimmunity retina background nodlike receptors nlrs critical innate immune activation induction adaptive t cell responses yet role autoinflammatory diseases central nervous system cns remains incompletely defined nlr nlrp12 reported inhibit promote neuroinflammation animal model multiple sclerosis experimental autoimmune encephalomyelitis eae t cellspecific role investigated uveitis resulting autoimmunity neuroretina extension cns involves breach immune privilege entry t cells eye examined contribution nlrp12 t cellmediated model uveitis experimental autoimmune uveitis eau methods mice immunized interphotoreceptor retinoidbinding protein peptide 120 irbp120 emulsified complete freunds adjuvant cfa uveitis evaluated clinical histopathological scoring comparisons made wt vs nlrp12 mice lymphopenic rag1 mice reconstituted wt vs nlrp12 cd4+ t cells among bone marrow bm chimeric mice antigenspecific theffector responses evaluated elisa intracellular cytokine staining cellular composition uveitic eyes wt nlrp12 mice compared using flow cytometry expression nlrp12 cytokines chemokines within neuroretina evaluated immunoblotting quantitative pcr results nlrp12 mice developed exacerbated uveitis characterized extensive vasculitis chorioretinal infiltrates photoreceptor damage nlrp12 dispensable t cell priming differentiation peripheral th1 th17 cells uveitis immunodeficient mice reconstituted either nlrp12 wt t cells similar collectively ruled t cells source nlrp12mediated protection eau uveitic nlrp12 eyes pronounced myeloid cell accumulation uveitic wt eyes transplantation nlrp12 bm resulted increased susceptibility eau regardless host genotype interestingly nonhematopoietic origin nlrp12 function also observed indeed nlrp12 found constitutively expressed neuroretina suppressed chemokine cytokine induction conclusions data identify combinatorial role nlrp12 dampening autoimmunity neuroretina findings provide pathway development therapies uveitis potentially autoinflammatory autoimmune diseases cns keywords nlrp12 nodlike receptor pattern recognition receptor uveitis,0.0
intrathecal baclofen pumps neurologist needs know increasing numbers patients intrathecal baclofen pump implanted part spasticity management neurologists may asked management devices patients attend emergency departments unrelated illnesses occasionally intrathecal baclofen system will directly lead acute presentation furthermore presence intrathecal baclofen pump needs consideration requesting investigations particularly mr imaging review aims,0.0
effect selfacupressure fatigue patients multiple sclerosis abstract aim study conducted randomized controlled study evaluate effect selfacupressure fatigue patients multiple sclerosis ms method sample study consisted 123 patients 41 experiment group 40 sham group 42 controls admitted neurology clinic university hospital collect data patient information form fatigue severity scale fss expanded disability status scale edss minimental status examination used depressive mood sleep quality may affect fatigue evaluated using beck depression scale bdiii pittsburg sleep quality index psqi respectively patients experimental group applied acupressure use li4 gu sp6 san yin jiao st36 zu san li points results majority patients female 675 mean age 4118 addition mean bdiii score patients found 1554 mean score psqi 678 mean scores scales similar groups baseline fss score means examined significant difference among groups acupressure554 087 control540 092 sham550 099 p 0816 4th week significant decrease mean score fatigue experimental group compared two groups acupressure415 109 control547 111 sham534 114 p 0 001 conclusion results suggest acupressure might effective method reduce fatigue patients ms keywords acupressure depression fatigue multiple sclerosis sleep,0.0
impact secondary infections covid19 critically ill patients abstract available keywords covid19 sarscov2 infection blood chemistry parameters clinical outcome microbiological data secondary infections,0.0
new mri guidelines multiple sclerosis abstract english german background improve efficient use magnetic resonance imaging mri routine clinical practice expert panel revised guidelines use diagnosis monitoring multiple sclerosis ms objectives revised guidelines now take account new developments relevant advances knowledge ongoing debate safety related intravenous gadoliniumbased contrast agents value spinal cord mri diagnostic prognostic surveillance purposes reevaluated standardization brain spinal cord mri protocols diagnosis assessment prognosis monitoring therapy well use 3dflair threedimensional fluidattenuated inversion recovery important sequence diagnosis lesions brain included allows better interpretation comparability eg followup assessments zusammenfassung hintergrund die leitlinien zum einsatz der magnetresonanztomographie mrt bei der diagnose und berwachung von multipler sklerose ms wurden von einem expertengremium berarbeitet um einen effizienten einsatz der mrt der klinischen routinepraxis zu bekommen ziele die leitlinienrevision bercksichtigt nun neue entwicklungen und relevante wissensfortschritte wie die anhaltende diskussion um die sicherheit bezug auf intravense gadoliniumbasierte kontrastmittel der wert der spinalen mrt fr diagnostische prognostische und berwachungszwecke wurde neu evaluiert die standardisierung zerebraler und spinaler mrtprotokolle fr diagnostik einschtzung der prognose und therapiemonitoring sowie der einsatz der 3dflair fluidattenuated inversion recovery als wichtigste sequenz fr die zerebrale diagnostik wurden eingefhrt da dies eine bessere interpretation und vergleichbarkeit z b bei verlaufsbeurteilungen erlaubt keywords brain followup magnetic resonance imaging monitoring standard operating procedure,0.0
determining optimal virtual reality exergame approach balance therapy persons neurological disorders using rasch analysis longitudinal observational study background virtual reality vr exergames gained popularity rehabilitation persons neurological disorders addon therapy increase intensity training intensity strongly dependent motivation patient motivation can increased delivering variation within training challenging exercises however patients often underchallenged exergame difficulty often match patients ability rasch analysis can establish hierarchy exergame items order assist delivery patientcentered therapy objective aim study apply rasch model create hierarchical order existing vr balance exergames relate exergames abilities persons neurological disorders order deliver challenge variation methods total 30 persons stroke 51 persons multiple sclerosis ms included study participants performed training program lasting 3 weeks persons ms 4 weeks persons stroke performed vr balance exergames movement recognitionbased system mindmotion go mindmaze sa vr exercise scores berg balance scale scores clinical descriptive data collected berg balance scale device scores analyzed rasch model using repeatedmeasures approach examine whether distribution exercise scores fitted rasch model secondly personitem map created show hierarchy exercise difficulty person ability results participants completed selection 56 balance exercises ie items consisted combination various balance tasks levels ie exercises using repeated measures resulted count 785 observations analysis showed strong evidence unidimensionality data total 47 exercises ie items sufficiently good fit rasch model six items showed underfit outfit mean square values 15 one item showed underfit kept analysis three items negative pointbiserial correlations final model consisted 47 exercises provided persons low moderate balance ability conclusions vr exercises sufficiently fitted rasch model resulted hierarchical order vr balance exercises persons stroke ms low moderate balance ability combination berg balance scale results can guide clinical decisionmaking selection patientfocused vr balance exercises trial registration clinicaltrialsgov nct03993275 https clinicaltrialsgov ct2 show nct03993275 keywords rasch analysis balance digital therapeutics exergaming multiple sclerosis neurorehabilitation stroke virtual reality,0.0
light chain deposition disease masquerading smokingassociated nodular glomerulosclerosis deposits identified electron microscopy light chain deposition disease lcdd form monoclonal gammopathy renal significance diagnosis based immunofluorescence findings linear monoclonal light chain staining basement membranes throughout kidney appear nonorganized granular punctate powdery electron dense deposits electron microscopy em although lcdd without em deposits welldescribed lcdd identified em negative rare hardly,0.0
multimodal magnetic resonance imaging quantification gray matter alterations relapsingremitting multiple sclerosis neuromyelitis optica spectrum disorder herein combined neurite orientation dispersion density imaging noddi synthetic magnetic resonance imaging symri evaluate spatial distribution extent gray matter gm microstructural alterations patients relapsingremitting multiple sclerosis rrms neuromyelitis optica spectrum disorder nmosd noddi neurite density index ndi orientation dispersion index odi isotropic volume fraction isovf symri myelin volume fraction mvf,0.0
ms ms t2weighted imaging t2wi based radiomic findings distinguish ms mimics backgroundischemic vasculopathy particularly smallvessel disease may mimic multiple sclerosis ms located periventricular subcortical region magnetic resonance mr examinations included differential diagnosis mslike lesionsobjectiveto evaluate performance t2weighted imaging t2wi based radiomic signature distinguish ms lesions lesions corresponding ischemic demyelination often mimics ms mrimethodsa retrospective study conducted 38 patients 627 lesions ms 914 patients 2466 lesions lesions mimicking ischemic demyelination periventricular subcortical region patients underwent 3 t mri total 472 radiomic features extracted t2wi data patient intraclass correlation coefficients used select features excellent stability repeatability used minimumredundancy maximumrelevance mrmr least absolute shrinkage selection operator lasso algorithms feature selection feature selection various classifiers including logistic regression decision tree adaboost random forest rf support vector machine svm trained performance classifier validated test set determining area curve auc resultsnine features selected distinguish ms lesions similar lesions ischemic demyelination radiomic signature showed significant difference ms ischemic demyelination patients p 001 rf svm overfitted lasso logistic regression model bestperforming radiomic model auc accuracy sensitivity specificity 0900 95 ci 08830918 870 589 952 respectively training set 0828 95 ci 07910864 877 536 944 respectively validation setconclusionthe t2wibased radiomic signature can effectively differentiate ms patients patients mslike lesions due ischemic demyelination,0.0
systematic review tissue single cell transcriptome proteome studies brain multiple sclerosis multiple sclerosis ms inflammatory demyelinating degenerative disease central nervous system cns although inflammatory responses efficiently treated therapies progression scarce suboptimal biomarkers predict disease course insufficient cure preventive measures ms require knowledge core pathological events site tissue damage novelties systems biology emerged paved way finegrained,1.0
contribution neuroimmune crosstalk pain peripheral nervous system spinal cord pain unpleasant sensation associated injury inflammation infection demonstrated communication immune cells neurons plays vital role pain painrelated diseases eg multiple sclerosis osteoarthritis irritable bowel syndrome growing data preclinical clinical studies established bilateral regulations peripheral immune cells nociceptive neurons beneficial detrimental development,0.0
contrastenhanced double inversion recovery sequence patients multiple sclerosis feasibility subtraction images pre postcontrast images background reports examined feasibility postcontrast double inversion recovery dir magnetic resonance mr sequence patients multiple sclerosis ms partial complete signal loss enhancing ms lesions purpose compare subtracted images dir precontrast postcontrast dir images contrast enhanced t1weighted cet1w images depiction contrast enhancement ms lesions material methods total 27 patients included two neuroradiologists interpreted images cet1w imaging subtracted dir interpretation images classified score 15 5 definitely superior contrast lesions dir subtraction compared conventional cet1w imaging 1 definitely superior contrast lesions cet1w imaging interrater agreement coefficient measured signaltonoise ratio snr contrastnoiseratio cnr lesion compared results significant difference p 0001 scoring seen conventional cet1w imaging 21 15 one reviewer 24 15 dir subtraction 44 10 one reviewer 47 08 snr conventional cet1w imaging 248 147 significantly superior dir subtraction 40 10 p 0001 cnr dir subtraction 3264 2500 significantly superior conventional cet1w imaging 08 55 p 0001 interrater agreement evaluation contrast enhancement lesions coefficients 084 conventional cet1w imaging 072 dir subtraction conclusion subtracted dir image enables obvious contrast enhancement ms lesions compared conventional cet1w imaging keywords magnetic resonance imaging adults brain brain stem imaging sequences intravenous contrast agents,0.0
association dietary inflammatory index risk demyelinating autoimmune diseases background considering limited data association dietary inflammatory index dii demyelinating autoimmune diseases studied issue early diagnosed patients eg preceding multiple sclerosis ms diagnosing level clinically isolated syndrome cis radiologically isolated syndrome ris ms neuromyelitis optica spectrum disorder nmosd using casecontrol study among iranian population methods total 291 subjects selected,1.0
work stress loss years lived without chronic disease 18year followup 15 million employees denmark aimed examine association exposure work stress chronic disease incidence loss chronic diseasefree life years danish workforce study population included 1 592 491 employees aged 3059 2000 without prevalent chronic diseases assessed work stress combination job strain effortreward imbalance using job exposure matrices used cox regressions estimate risk incident hospitaldiagnoses death chronic diseases ie,0.0
evaluation plasma neurofilament light chain levels biomarker neuronal injury active chronic phases autoimmune neurologic disorders abstract objective evaluate plasma neurofilament light nfl levels autoimmune neurologic disorders ainds autoimmune encephalitis ae background particular neural autoantibody syndrome different clinical phenotype making one unifying clinical outcome measure difficult assess heterogeneous group disorders final common pathway likely cns damage inflammation defining biomarker cns injury easily obtainable blood sample reflects positive treatment response highly advantageous future therapeutic trials measurement blood concentration neurofilament light nfl chain however may provide biomarker central nervous system cns injury ae ainds provide initial evaluation plasma nfl levels ae well ainds active chronic phases disease demonstrate potential utility minimallyinvasive biomarker ae ainds design methods patients retrospectively identified enrolled biorepository rocky mountain ms center university colorado prospectively enrolled initial presentation patients welldefined aind followed 2014 2021 nfl tested using single molecule array simoa technology patients headaches without significant neurologic disease included controls results twentysix plasma 14 csf samples patients ainds 20 plasma control samples stored biorepository evaluated positive correlation found plasma csf nfl levels patients aind r 2 083 p 0001 elevated plasma levels nfl seen patients active ae compared controls geometric mean gm 514 vs 64 pg ml p 0002 patients chronic symptoms 6 months since new worsening symptoms ae cerebellar ataxia ca showed trend toward lower plasma nfl levels gm 151 pg ml compared active ae ca six patients longitudinal prospective sampling available demonstrated trend decreased plasma nfl levels time conclusions findings support use plasma nfl potential minimallyinvasive biomarker cns injury keywords autoimmune encephalitis ae autoimmune neurological disorders biomarker cerebellar ataxia neurofilament nf neurofilament light nfl chain,0.0
patientcentered framework rehabilitation research outpatient settings conducting high quality clinical research dependent merging scientific rigor clinical environment often complex endeavor may include numerous barriers competing interests overcoming challenges successfully integrating clinical research programs clinical practice settings serving rehabilitation outpatients beneficial logistical perspective eg supports efficient successful research procedures establishment,0.0
platelets thromboinflammation neurovascular disease brain spinal cord immuneprivileged organs disease state protection mechanisms blood brain barrier bbb ineffective overcome pathological processes neuroinflammatory diseases microglia cells resident immune cells contribute local vascular inflammation potentially systemic inflammatory response taking place parallel microglia cells interact cells impacting integrity bbb propagate,0.0
role cxcl13 cxcr5 axis autoimmune diseases cxcl13 bcell chemokine produced mainly mesenchymal lymphoid tissue organizer cells follicular dendritic cells human t follicular helper cells binding receptor cxcr5 cxcl13 plays important role lymphoid neogenesis lymphoid organization immune responses recent studies found cxcl13 receptor cxcr5 implicated pathogenesis several autoimmune diseases rheumatoid arthritis multiple sclerosis systemic lupus erythematosus,0.0
diffusion tensor imaging revealed microstructural changes normalappearing white matter regions relapsingremitting multiple sclerosis conclusion study revealed widespread microstructure changes nawm rrms patients readymade wm atlas probabilistic lesion map findings support hypothesis demyelination accumulation inflammatory cells axonal injury nawm rrms dtibased metrics considered potential noninvasive biomarkers disease severity,1.0
pain prevalence multiple sclerosis lisbon tertiary hospital crosssectional study conclusion pain important symptom group patients ms significantly interfered mood general activity regular work maximum intensity pain felt patients significant 677 patients analgesic treatment mean pain relief 54 nsaids used drugs followed gabapentinoids acetaminophen management pain medical community must continue study population order improve approach,0.0
unique case radiologically isolated syndrome diagnosed followup cytomegalovirus meningoencephalitis radiologically isolated syndrome ris refers entity mri brain spine demonstrates incidental white matter lesions characteristic demyelinating disease morphology location highrisk ris may require diseasemodifying treatment dmt complex interaction among genetic environmental factors leads selfreactive immune mechanisms believed pivotal role pathogenesis demyelinating diseases viruses,1.0
novel emtbk1 em variant lys694del presenting corticobasal syndrome family ftdals spectrum diseases case report several variants tankbinding kinase 1 tbk1 gene associated frontotemporal dementia amyotrophic lateral sclerosis ftdals spectrum diseases corticobasal syndrome cbs characterized asymmetric limb rigidity dystonia myoclonus association speech limb apraxia cortical sensory deficit alien limb can result variety underlying pathologies although typically sporadic occasionally associated mapt grn,0.0
dysregulation survivintargeting micrornas autoimmune diseases new perspectives novel therapies well established etiopathogenesis diverse autoimmune diseases rooted autoreactive immune cells excessively proliferative state impaired apoptotic machinery survivin antiapoptotic mitotic factor sparked considerable research interest field survivin overexpression shown contribute significantly development autoimmune diseases via autoreactive immune cell overproliferation apoptotic dysregulation,0.0
effect fingolimod healthrelated quality life paediatric patients multiple sclerosis results phase 3 paradigms study background paradigms study fingolimod demonstrated superior efficacy versus interferon ifn 1a comparable overall incidence adverse events slightly higher rate serious adverse events patients paediatriconset multiple sclerosis poms report healthrelated quality life hrqol outcomes paradigms methods patients poms n215 aged 1018 years randomised oncedaily oral fingolimod n107 onceweekly intramuscular ifn 1a n108 hrqol outcomes assessed using 23item pediatric quality life pedsql scale comprises physical psychosocial health summary scores including emotional social school functioning post hoc inferential analysis evaluated changes selfreported parentreported pedsql scores baseline 2 years treatment groups using analysis covariance model results treatment fingolimod showed improvements versus ifn 1a pedsql scale selfreported parentreported total scale scores 466 vs 116 p0001 271 vs 102 p005 respectively proportion patients achieving clinically meaningful improvement pedsql total scale score two times higher fingolimod versus ifn 1a per selfreported scores 475 vs 242 p0001 fingolimod favoured versus ifn 1a per parentreported scores 378 vs 247 pnonsignificant group differences selfreported total scale scores favour fingolimod pronounced among patients 2 relapses year prior study entry showed improving stable expanded disability status scale scores study conclusion fingolimod improved hrqol compared ifn 1a patients poms evidenced selfreported parentreported pedsql scores keywords multiple sclerosis paediatric neurology quality life,0.0
motor preparation impairment multiple sclerosis evidence bereitschaftspotential simple complex motor tasks abstract objectives multiple sclerosis ms chronic inflammatory disease central nervous system characterized accumulation demyelinating lesions axonal loss course study aimed increase current knowledge motor preparation condition assessing two components bereitschaftspotential bp1 bp2 also known readiness potential methods twelve patients ms ten age gendermatched healthy controls hc included patients demographic clinical data collected participants asked perform two different tasks simple index extension luria sequence bp1 bp2 values obtained 18 central electroencephalography electrodes compared two groups results compared hc patients ms showed earlier bp1 onset ie longer latency almost analyzed scalp regions index extension also observed luria sequence centroparietal regions bp2 latency significant difference noted groups either task regard amplitudes patients ms larger bp1 amplitudes right frontocentral area index extension greater bp1 bp2 amplitudes bilateral centroparietal left central regions luria task bp1 latency also found significantly correlated disease duration performance executive function tests trail making test conclusions study showed first time changes bereitschaftspotential patients ms data reflect prolonged movement preparation population may suggest global alteration premotor scheme keywords bereitschaftspotential movement preparation multiple sclerosis premotor scheme readiness potential,1.0
multiple sclerosis relationship locus control quality life persons low versus high disability background health locus control hloc degree individuals believe health outcomes controlled external factors environmental forces chance fate people higher power internal factors behavior action literature hloc associates internal health locus control ihloc prohealth behaviors better health outcomes however studies also suggest chronic illnesses external,0.0
smoking attributable risk multiple sclerosis tobacco smoke important modifiable environmental risk factor multiple sclerosis ms risk population attributable fraction af ms due smoking can used assess contribution smoking risk ms development conducted matched casecontrol study including individuals ms populationbased controls overall sex genetic risk scorestratified af due smoking calculated fitting logistic regression models included 9 419 individuals,0.0
health related quality life perceived social support french lebanese ms patients comparative study abstractbackgroundthe perception diagnosis announcement social support coping strategies seem determining factors quality life multiple sclerosis ms patients possible transcultural variations study explores psychosocial dimensions lebanese french ms patientsmethodsfor crosssectional multicenter study 8 questionnaires used assess quality life family support coping strategies mood fatigue stress hopelessness ms patients 7 translated arabic back translated french administered group lebanese ms patients compared ms sample france data collected populations analyzedresultsa total 107 patients included 46 lebanese 61 french majority ms patients young females high level education relapsing remitting form ms low level disability populations exhibited comparable quality life answers questionnaires regarding mood disorders hopelessness perceived stress however french patients significantly fatigue perceived social support given family considered greater french group compared lebanese one also maladaptive coping strategies selfdistraction denial behavioral disengagement substance use selfblame venting used frequently french population compared lebanese correlated higher anxiety scores diagnosis communication overall brief informative satisfying populationsconclusionthis study highlighted transcultural differences french lebanese ms patients mainly social support coping strategies,0.0
impact diseasemodifying therapies mri outcomes patients relapsing remitting multiple sclerosis systematic review network metaanalysis abstractbackgroundmultiple sclerosis ms chronic autoimmune inflammatory demyelinating disorder central nervous system clinical presentation supported characteristic findings mri forms backbone current diagnostic criteria study aimed investigate efficacy based mri outcomes fda approved diseasemodifying therapies dmts relapsingremitting ms rrms materials methodswe searched pubmed embase cochrane central register controlled trials randomised controlled trials rcts dmts outcome measures mean number t2 new enlarging lesions new t1 gadoliniumenhancing gd+ t1 hypointense t1 lesions brain mri performed 12 months 24 months performed network metaanalysis using frequentist approach stata version 160resultswe identified 26 rcts final analysis interferon 1a placebo common comparison treatment ocrelizumab effective reducing number gd+t1 lesions dimethyl fumarate 480mg relatively better reducing number new t2 lesions treatment ranking showed ocrelizumab dimethyl fumarate 480mg efficacious 1 09 sucra respectively reducing number new gd+t1 hypointense lesions dimethyl fumarate 480mg 720mg natalizumab efficacious 10 09 08 sucra respectively reduce number new t2 lesionsconclusionocrelizumab dimethyl fumarate 480 720mg natalizumab demonstrated favourable mri outcomes patients rrms,1.0
impact diseasemodifying therapies mri outcomes patients relapsing remitting multiple sclerosis systematic review network metaanalysis background multiple sclerosis ms chronic autoimmune inflammatory demyelinating disorder central nervous system clinical presentation supported characteristic findings mri forms backbone current diagnostic criteria study aimed investigate efficacy based mri outcomes fda approved diseasemodifying therapies dmts relapsingremitting ms rrms materials methods searched pubmed embase cochrane central register controlled trials randomised controlled trials rcts dmts outcome measures mean number t2 new enlarging lesions new t1 gadoliniumenhancing gd+ t1 hypointense t1 lesions brain mri performed 12 months 24 months performed network metaanalysis using frequentist approach stata version 160results identified 26 rcts final analysis interferon 1a placebo common comparison treatment ocrelizumab effective reducing number gd+t1 lesions dimethyl fumarate 480 mg relatively better reducing number new t2 lesions treatment ranking showed ocrelizumab dimethyl fumarate 480 mg efficacious 1 09 sucra respectively reducing number new gd+t1 hypointense lesions dimethyl fumarate 480 mg 720 mg natalizumab efficacious 10 09 08 sucra respectively reduce number new t2 lesionsconclusion ocrelizumab dimethyl fumarate 480 720 mg natalizumab demonstrated favourable mri outcomes patients rrms,1.0
health related quality life perceived social support french lebanese ms patients comparative study backgroundthe perception diagnosis announcement social support coping strategies seem determining factors quality life multiple sclerosis ms patients possible transcultural variations study explores psychosocial dimensions lebanese french ms patientsmethodsfor crosssectional multicenter study 8 questionnaires used assess quality life family support coping strategies mood fatigue stress hopelessness ms patients 7 translated arabic back translated french administered group lebanese ms patients compared ms sample france data collected populations analyzedresultsa total 107 patients included 46 lebanese 61 french majority ms patients young females high level education relapsing remitting form ms low level disability populations exhibited comparable quality life answers questionnaires regarding mood disorders hopelessness perceived stress however french patients significantly fatigue perceived social support given family considered greater french group compared lebanese one also maladaptive coping strategies selfdistraction denial behavioral disengagement substance use selfblame venting used frequently french population compared lebanese correlated higher anxiety scores diagnosis communication overall brief informative satisfying populationsconclusionthis study highlighted transcultural differences french lebanese ms patients mainly social support coping strategies,0.0
sociodemographic clinical characteristics people multiple sclerosis neuromyelitis optica spectrum disorder central northern region chile prevalence study background scarcity information prevalence demyelinating diseases chile latin american countries aim study determine prevalence multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd region centralnorthern chilemethods crosssectional study performed patients region confirmed diagnosis ms nmosd control program end 2020 included study totalling sixty patients diagnosis ms eight patients nmosd sociodemographic clinical variables patients recorded neurologists charge ms programs public private facility coquimbo region january march 2021results prevalence ms 718 per 100 000 inhabitants 95 ci 536899 nmosd 095 per 100 000 population 95 ci 09162 diseases several times prevalent women men female male ratio ms 51 nmosd 71 mean age diagnosis 322 ms 322 years nmosd relevant risk factors identified terms type ms 866 patients diagnosis relapsingremitting ms 67 primary progressive ms 67 secondary progressive ms overall 20 patients ms 125 nmosd presented score 5 expanded disability status scale 875 nmosd patients receiving rituximabconclusion prevalence demyelinating diseases centralnorthern region chile corresponds reported rates latin american countries important contribution given scarcity evidence prevalence demyelinating diseases chile illnesses mainly affect young adult women cause disability among productive adults,1.0
validity responsiveness score interpretation promisnq physical function multiple sclerosis 15a short form multiple sclerosis background valid sensitive patientreported outcome pro measure physical function pf people multiple sclerosis ms substantial value routine care clinical research now describe development promisnq short form v20 pf multiple sclerosis 15a promisnq pf ms 15a assessing pf relapsing progressive ms also validity reliability responsiveness promisnq pf ms 15a evaluated minimal important difference mid thresholds score change estimated score interpretation guide developedmethods mixedmethods sequential design employed relevant pf concepts elicited semistructured interviews people relapsing ms mapped promis pf item bank measurement experts integrated results interviews people ms input panel neurologists generate draft short form relevance comprehensiveness draft short form assessed cognitive debriefing interviews people relapsing progressive ms subsequently item reduction evaluation psychometric properties performed two observational studies crosssectional study us n296 96week longitudinal study uk ms register cohort n558 main outcomes measures estimates knowngroups validity convergent validity reliability responsiveness mid worseningresults factor analyses supported unidimensionality newly derived 15item short form cronbachs alpha 097 intraclass correlation coefficient 097 testretest scores 527 days indicated strong reliability convergent validity demonstrated moderatetostrong correlations scores related pro measures scores discriminated among patient groups classified levels physical health criteria score changes 2126 points proposed mid criteria minimal worsening pfconclusion promisnq pf ms 15a demonstrated reliability validity sensitivity change input patients clinicians ensured content comprehensive relevant people ms,0.0
chemobrain mitoxantroneinduced oxidative stress apoptotic autophagic neuronal death adult cd1 mice mitoxantrone mtx topoisomerase ii inhibitor used treat wide range tumors multiple sclerosis associated potential neurotoxic effects mediated hitherto poorly understood mechanisms adult male cd1 mice underlying neurotoxic pathways clinically relevant cumulative dose 6 mg kg mtx evaluated biweekly administration 3 weeks sacrifice 1 week last administration undertaken oxidative stress neuronal damage apoptosis,0.0
acetyl11ketoboswellic acid improves clinical symptoms modulation nrf2 nfb pathways sjl j mouse model experimental autoimmune encephalomyelitis multiple sclerosis ms characterized chronic autoimmune inflammation central nervous system cns ie brain spinal cord autoimmune inflammation cns periphery causes demyelination axons ultimately leading clinical symptoms gait imbalance lack coordination paraplegia innate immune cells dendritic cells neutrophils play critical role initiation progression ms upregulation oxidants two prominent pathways,1.0
therapeutic plasma exchange pediatric patients acute demyelinating syndromes central nervous system singlecenter experience background therapeutic plasma exchange tpe extracorporeal treatment can used adult pediatric patients acute demyelinating syndromes central nervous system study efficacy safety tpe evaluated 10 pediatric patients underwent tpe unresponsive corticosteroid treatment methods records 10 pediatric patients underwent tpe pediatric intensive care unit picu may 2017 june 2020 used expanded disability status scale edss gait scale gs visual outcome scale vos applied patients tpe results 10 patients underwent tpe five diagnosed multiple sclerosis ms three transverse myelitis tm two acute disseminated encephalomyelitis adem median age patients 133 years iqr 815 median day symptom onset onset tpe 125 days iqr 728 total 104 tpe sessions performed successfully complications encountered three patients sessions common complication hypofibrinogenemia decrease edss gs scores found consistent clinical response patients statistically significant decrease vos conclusions study can say tpe feasible effective safe treatment modality children acute demyelinating syndromes central nervous system keywords therapeutic plasma exchange acute demyelinating syndromes children,1.0
characterization modification kelchlike echassociated protein 1 different fumarates fumarates fumaric acid esters primarily dimethyl fumarate dmf monoethyl fumarate mef salts orally administered systemic agents used treatment psoriasis multiple sclerosis widely believed pharmaceutical activities fumarates exerted keap1nrf2 pathway although revealed dmf mef differentially modify specific keap1 cysteine residues result differential activation nrf2 modification,0.0
multiple interventions thoracoabdominal aortic aneurysm child tuberous sclerosis thoracoabdominal aortic aneurysms toddlers extremely rare however experienced extent iii thoracoabdominal aortic aneurysm male tuberous sclerosis underwent three open repairs one endovascular aortic repair age 4 18 case highlights potential severe recurrent vascular aneurysms thoracic abdominal aorta complication tuberous sclerosis children although aortic aneurysms children rare vital,0.0
personality association selfmanagement multiple sclerosis background healthcare system aims empower patient selfmanagement becomes increasingly important multiple sclerosis effective selfmanagement associated various favorable healthrelated outcomes like improvement quality life reduction depression anxiety symptoms reduced healthcare costs study investigates association big five personality traits selfmanagement including activity selfhelp groupsmethods people ms recruited via several paths within germany eg medical practices social events german ms society final study sample consisted 682 participants answered multidimensional questionnaire comprised bigfiveinventory10 personality health education impact questionnaire heiq selfmanagement competencies questions participation selfhelp groups sociodemographic clinical variablesresults multivariate regression analyses showed personality explain greater amount variance selfmanagement sociodemographic clinical variables neuroticism strongest predictor correlated negatively heiqdimensions selfmanagement contrast logistic regression analysis none big five traits became significant predicting activity selfhelp groupsconclusion expected personality plays important role regarding selfmanagement ideally timesaving personality assessment considered routine clinical practice identify patients risk however minimum personality traits considered consultations neurologists may need help understand benefits effective selfmanagement receive support improve selfmanagement skills reduce neuroticism lower risk secondary complications,0.0
radiomics 3dimensional magnetic resonance fingerprinting influence dictionary design repeatability reproducibility radiomic features abstract objectives aimed investigate influence magnetic resonance fingerprinting mrf dictionary design radiomic features using vivo human brain scans methods scanrescans threedimensional mrf conventional t1weighted imaging performed 21 healthy volunteers 9 males 12 females mean age 413 146 years age range 2272 years five patients multiple sclerosis 3 males 2 females mean age 412 73 years age range 3253 years also included mrf data reconstructed using various dictionaries different step sizes first secondorder radiomic features extracted dataset intradictionary repeatability interdictionary reproducibility evaluated using intraclass correlation coefficients iccs features iccs 090 considered acceptable relative changes calculated assess interdictionary biases results overall scanrescan iccs mrfbased radiomics ranged 086 095 depending dictionary step size significant differences observed overall scanrescan repeatability mrfbased radiomic features conventional t1weighted imaging p 100 intradictionary repeatability insensitive dictionary step size differences mrfbased radiomic features varied among dictionaries overall icc interdictionary reproducibility 062099 especially step sizes large firstorder gray level cooccurrence matrix features reproducible feature classes among different step size dictionaries t1 mapderived radiomic features provided higher repeatability reproducibility among dictionaries obtained t2 maps conclusion mrfbased radiomic features highly repeatable various dictionary step sizes caution warranted performing mrfbased radiomics using datasets containing maps generated different dictionaries key points mrfbased radiomic features highly repeatable various dictionary step sizes use different mrf dictionaries may result variable radiomic features even mrf acquisition data used caution needed performing radiomic analysis using data reconstructed different dictionaries keywords brain magnetic resonance imaging neuroimaging repeatability reproducibility results,0.0
synthesis biological evaluation artemisinin derivatives potential ms agents paper series artemisinin derivatives synthesized evaluated studies shown ifn produced th1 cd4 + t cells il17a secreted th17 cd4 + t cells played critical roles treatment multiple sclerosis used different concentrations artemisinin derivatives inhibit th1 th17 differentiation naive cd4 + t cells characterize ifn il17a vitro experiments preliminary screening results showed ester compound 5,0.0
evaluation peripapillary subfoveal choroidal vascularity index patients multiple sclerosis conclusion pcvi sfcvi scores significantly lower ms patients compared healthy controls pcvi scores ms patients history significantly lower patients without previous attack sfcvi scores consider evaluation pcvi sfcvi might useful monitoring ocular involvement patients ms,0.0
spermine alleviates experimental autoimmune encephalomyelitis via regulating t cell activation differentiation multiple sclerosis ms chronic neuroinflammatory disease causes demyelination axonal damage even disability th1 th17 cells precisely ifn il17a double producing cd4 + t cells known play critical roles pathogenesis ms eae mouse model ms polyamines regulate immune system also essential normal function central nervous system cns study demonstrate supplementation,1.0
sarscov2 triggered relapse multiple sclerosis abstract objectives indications sarscov2 can trigger new onset relapses neuroimmunological disease report patient relapsing remitting multiple sclerosis rrms diseasemodifying therapy dmt experienced relapse rrms mild covid19 case report patient 27yearold female rrms developed third exacerbation rrms dmt two weeks mild covid19 compared previous imaging findings new studies revealed increase lesion load enhancing lesion two segments thoracic spine patient profited steroids replacement previous dmt tolerated first sarscov2 vaccination without side effects 6 months sarscov2 infection conclusions sarscov2 infections can followed exacerbation ms failure dmt arguments favour causal relation can raised neurologist remain vigilant new relapsing neuroimmunological disease following sarscov2 infections keywords covid19 central nervous system multiple sclerosis relapse sarscov2,0.0
finnish multiple sclerosis patients treated cladribine tablets nationwide registry study background cladribine tablets adult patients highly active relapsing multiple sclerosis ms available finland since 2018 realworld data different genetic geographical backgrounds needed complement data clinical trialsmethods investigated use cladribine tablets finland noninterventional cohort study based realworld data nationwide finnish ms registry eligible patients initiated treatment cladribine tablets 20182020 included descriptive analyses outcomes conducted using summary statistics timedependent endpoints analyzed using cumulated events analysis based 1kaplanmeier estimates curves subgroups analyzed separately according number previous diseasemodifying therapies dmts common last preceding therapiesresults data 179 patients analyzed median followup time 190 months interquartile range iqr 120262 134 patients followed least 12 months 112 patients 836 remained relapsefree followup mean annualized relapse rate arr 10 standard deviation sd 089 baseline 01 sd 030 followup patients two previous dmts shorter time first relapse median 25 months iqr 0693 compared patients 01 previous dmts median 114 months iqr 87131 p0013 excluding patients switching fingolimod n33 statistically significant difference time first relapse longer observed two groups p0252 adverse events aes reported 30 patients 168 frequent ae headache n14 78 one patient 06 died cardiac arrest discontinuation cladribine tablets reported nine patients 50 conclusion mean arr observed cohort similar reported clinical trials approximately half patients used two previous dmts cladribine tablets patients shorter time first relapse compared patients 01 previous dmts mostly driven early relapses patients switching fingolimod,0.0
functions astrocytes multiple sclerosis review backgroundmultiple sclerosis ms chronic autoimmune disease central nervous system cns usually affects young adults 20 40 years old chronic neurodegenerative diseases multiple sclerosis cns cells take several adaptations neuroinflammation main cells involved inflammatory process glial cells astrocytes stand cells play complex role several studies report reactive astrocytes lose supporting role gain toxic function progression diseasesresultsthe beneficial injurious effects group cells ms addressed work well drugs already used treatment patients multiple sclerosis aiming regulate astrocytic activitiesconclusionsthe knowledge functions astrocytes essential expansion scientific research area since cells important involved different mechanisms action especially neurodegenerative autoimmune diseases,0.0
identification potential key genes immune infiltration multiple sclerosis backgroundmultiple sclerosis ms extremely serious autoimmune disease nervous system extensive evidence indicated immune system activation plays crucial role development ms however exact mechanism ms still well understood objective identify potential key genes multiple sclerosis ms via bioinformatic analysis apply cibersort algorithms calculate proportion infiltrating immune cellsmethodsthe differentially expressed genes degs analyzed two public datasets included 99 ms 45 controls 133 ms 79 controls common degs obtained p 005 lasso regression analysis performed common degs gse17048 receiver operating characteristic roc curves created key genes screened based area receiver operating characteristic curve auc cibersort algorithms used explore immune infiltration msresults516 common degs screened two public datasets 54 signature genes obtained constructing lasso model ms4a6a cacna1i c9orf46 eif4ebp2 sertad2 tgfbr2 rab34 largest auc values selected key genes neutrophils monocytes resting memory cd4+ t cells cd8+ t cells resting nk cells accounted large proportion infiltrating immune cells msconclusionms4a6a cacna1i c9orf46 eif4ebp2 sertad2 tgfbr2 rab34 may closely related pathogenesis ms may represent new candidate biomarkers addition immune cell infiltration may also play important role progression ms,0.0
btk inhibition limits bcelltcell interaction modulation bcell metabolism implications multiple sclerosis therapy inhibition brutons tyrosine kinase btki now viewed promising nextgeneration bcelltargeting therapy autoimmune diseases including multiple sclerosis ms surprisingly little known however btki influences ms diseaseimplicated functions b cells demonstrate addition expected impact bcell activation btki attenuates bcelltcell interactions via novel mechanism involving modulation bcell metabolic pathways turn,0.0
physicochemical investigation novel curcumin diethyl aminobutyrate carbamate ester prodrug curcumin enhanced antineuroinflammatory activity curcumin polyphenol compound alleviates several neuroinflammationrelated diseases including alzheimers disease parkinsons disease multiple sclerosis epilepsy cerebral injury however therapeutic efficacy curcumin limited poor physicochemical properties present study aimed develop new carrierlinked curcumin prodrug curcumin diethyl aminobutyrate cur2ge improved physicochemical antineuroinflammatory properties cur2ge designed,0.0
multiple sclerosis relapses following cessation fingolimod background growing interest issue disease reactivation multiple sclerosis following fingolimod cessation relatively little known modifiers risk postcessation relapse including delay commencement new therapy prior disease activity objective aimed determine rate relapse following cessation fingolimod identify predictors relapse following cessation methods data extracted msbase registry march 2019 inclusion criteria clinically definite relapsing multiple sclerosis b treatment fingolimod 12 months c followup cessation 12 months d least one expanded disability status scale score recorded 12 months cessation results total 685 patients identified met criteria mean annualised relapse rate 171 95 ci 159 185 year prior fingolimod 050 95 ci 044 055 fingolimod 043 95 ci 038 049 fingolimod 218 32 patients experienced relapse first 12 months predictors higher relapse rate first year younger age fingolimod cessation higher relapse rate year prior cessation delaying commencement new therapy switching lowefficacy therapy conclusions disease reactivation following fingolimod cessation common younger patients greater disease activity prior cessation switch lowefficacy therapy,0.0
association pregnancies risk multiple sclerosis background pregnancies impact disease course multiple sclerosis ms relationship ms risk yet unclear objective determine relationships pregnancies gynecological diagnoses ms risk methods retrospective casecontrol study assessed differences gynecological international classification diseases 10th revision icd10 code recording rates women ms n 5720 crohns disease n 6280 psoriasis n 40 555 women without autoimmune diseases n 26 729 5 years diagnosis results twentyeight icd10 codes recorded less frequently women ms compared women without autoimmune disease 18 pregnancyrelated adjustment pregnancies codes unrelated pregnancies still negatively associated ms sensitivity analysis excluding women evidence possible demyelinating events diagnosis associations pronounced comparison women psoriasis associations confirmed true comparison women crohns disease conclusion findings provide evidence possible protective effect pregnancies ms risk likely independent addition previously suggested reversed causality negative associations gynecological disorders disease risk need investigation associations might shared different autoimmune diseases keywords multiple sclerosis autoimmune diseases casecontrol studies health services research pregnancy risk factors,1.0
immunomodulatory effects curcumin systemic autoimmune diseases systemic autoimmune diseases like rheumatoid arthritis multiple sclerosis systemic lupus erythematosus represent various autoimmune conditions identified immune system dysregulation activation immune cells autoantigen outbreak inflammation multiorgan impairment observed disorders immune system essential complex network cells chemical mediators defends organisms integrity foreign microorganisms precise operation,0.0
therapeutic plasma exchange tpe complications patients multiple sclerosis ms clinically isolated syndrome cis report tertiary center background therapeutic plasma exchange tpe conventional secondline treatment patients multiple sclerosis ms clinically isolated syndrome steroidrefractory relapses methods ms clinically isolated syndrome patients steroidrefractory relapse fulfilled indications tpe enrolled study expert nurse recorded data comprising age sex type ms disease modifying therapy disease duration relapse rate vital signs beginning end plasma exchange session plasma exchange volume normal saline volume tpe complications ultimately statistical association estimated amongst variables results total 122 cases assessed twelve cases 98 received plasmapheresis second time mean age 32287 years 107 877 female total 609 plasma exchange sessions completed hypotension skin reaction clinical complications hemoglobin loss hypokalemia laboratory complications fiftyfour cases 443 complications 40 328 1 complication 21 172 2 complications 6 49 3 complications 1 08 disclosed 4 complications relapse rate past 12 months mean plasma volume exchange significantly different groups conclusions revealed tpe considered safe secondline therapy ms relapses hypotension skin reaction hemoglobin loss hypokalemia complications tpe patients,0.0
dynamics retinal vessel loss acute optic neuritis patients relapsing multiple sclerosis background objectives rarefication retinal vasculature measured optical coherence tomography angiography octa novel finding patients multiple sclerosis ms study aimed analyze longitudinal dynamics retinal vasculature following acute inflammatory relapse including acute optic neuritis search associations alterations retinal architecture visual function,0.0
treatment adherence injectable treatments pediatric growth hormone deficiency compared injectable treatments chronic pediatric conditions systematic literature review conclusions adherence rhgh treatment high 80 many studies though comparability studies limited given substantial heterogeneity way adherence defined measured reported address heterogeneity recommend standardizing adherence defined reported encourage use standardized study designs outcome measures,0.0
mendelian randomization analysis suggests associations herpes simplex virus infections multiple sclerosis previous studies suggested association infection herpes simplex virus hsv liability multiple sclerosis ms remains largely unknown whether effect causal performed twosample mendelian randomization mr study explore relationship genetically predicted hsv infection ms risk genetic instrumental variables diagnosed infections hsv p 5 10 6 retrieved finngen study single nucleotide,0.0
four selfefficacy trajectories among people multiple sclerosis clinical associations implications background longitudinal studies among people multiple sclerosis pwms shown selfefficacy linked physical cognitive psychological functioning objectives determine distribution selfefficacy large sample pwms examining whether distinct groups show different selfefficacy trajectories time health status characteristics groups identified methods participants completed serial questionnaire packs including unidimensional selfefficacyms usems scale trajectories outcome neurological conditionsms tonicms study average 46month period resulting longitudinal data analysed groupbased trajectory model results 5887 pwms studied mean age 502 years sd 120 736 female relapsing remitting ms 618 secondary progressive 229 primary progressive 111 rapidly evolving relapsing remitting ms 42 four distinct selfefficacy trajectories emerged declining slightly declining stable improving selfefficacy showing different patterns health status indicators eq5d5l disability depression usems 18 baseline detected participants two declining groups conclusion future trials interventions selfefficacy assume priori low levels selfefficacy usems 18 baseline likely declining trajectory may need different interventions stable selfefficacy keywords multiple sclerosis patient reported outcome measures selfefficacy tonic study trajectories,0.0
ifngammaprimed hucmscs significantly reduced inflammation via foxp3 rorgammat stat3 signaling pathway animal model multiple sclerosis previous study showed interferon gamma ifn might enhance immunosuppressive properties mesenchymal stem cells mscs upregulating expression indoleamine 2 3dioxygenease therefore treated experimental autoimmune encephalomyelitis eae mice animal model multiple sclerosis ms ifnprimed human umbilical cord mscs ifnhucmscs study aimed investigate potential therapeutic effects ifnhucmscs transplantation identify,1.0
relaxationcompensated chemical exchange saturation transfer mri brain 7t application relapsingremitting multiple sclerosis chemical exchange saturation transfer cest magnetic resonance imaging mri can probe tissue biochemistry vivo high resolution sensitivity without requiring exogenous contrast agents applying cest mri ultrahigh field provides advantages increasing spectral resolution improving sensitivity metabolites faster proton exchange rates glutamate critical neurotransmitter brain prior magnetic resonance spectroscopy cest mri studies revealed,0.0
corrigendum curcumin betadglucuronide modulates autoimmune model multiple sclerosis altered gut microbiota ileum feces abstract corrects article doi 103389 fcimb2021772962 keywords alpha diversity picrust analysis animal model bacterial taxonomy bioinformatics confidence interval histology pattern matching,0.0
type interferon transcriptional network regulates expression coinhibitory receptors human t cells although inhibition t cell coinhibitory receptors revolutionized cancer therapy mechanisms governing expression human t cells elucidated present study show type 1 interferon ifni regulates coinhibitory receptor expression human t cells inducing pd1 tim3 lag3 inhibiting tigit expression hightemporalresolution mrna profiling ifni responses established dynamic regulatory networks uncovering three temporal transcriptional,0.0
multiple sclerosis cortical lesion detection deep learning ultrahighfield mri manually segmenting multiple sclerosis ms cortical lesions cl extremely timeconsuming past studies shown moderate interrater reliability accelerate task developed deep learningbased framework claims cortical lesion artificial intelligencebased assessment multiple sclerosis automated detection classification ms cl 7t mri two 7t datasets acquired different sites considered first consisted 60 scans include,0.0
effect intermittent vs continuous walking distance fatigue persons multiple sclerosis conclusion sample iw allowed pwms perform greater volume walking can option improve walking endurance populationimplications rehabilitationmultiple sclerosis ms disease progressively impacts walking resulting decrease maximum distance person ms can walkintermittent walking shown improve 6min walk test performance persons ms pwms compared continuous walking effects longer,0.0
natalizumab treatment pregnancy multiple sclerosis reappraisal maternal infant outcomes 6 years abstract objectives assess impact timing natalizumab cessation redosing longterm maternal infant outcomes 72 original 74 pregnancies italian pregnancy dataset multiple sclerosis ms methods maternal outcomes patients received natalizumab conception restarted drug within 1 month delivery treatment approach ta patients stopped natalizumab conception restarted drug later 1 month delivery conservative approach ca compared multivariable cox regression analyses pediatric outcomes assessed semistructured questionnaire results mean followup 61 years ca hazard ratio hr 41 95 ci 16106 p 0003 predictor relapse occurrence worsening expanded disability status scale edss associated higher annualized relapserate followup hr 33 95 ci 1479 p 0007 found major development abnormalities children discussion data confirm ta reduces risk disease activity observe increase major development abnormalities child keywords multiple sclerosis disability worsening infant outcomes natalizumab pregnancy,0.0
differences ms clinical epidemiological characteristics ashkenazi nonashkenazi jewish patients israel retrospective single center study prevalence severity multiple sclerosis ms varies across different ethnicities tendency severe phenotype noncaucasian populations objective evaluate differences disease phenotype ashkenazi jewish nonashkenazi jewish patients israel conducted single center retrospective cohort study subjects assigned ashkenazi nonashkenazi groups according selfreported ancestry disease severity assessed,0.0
measurement antisuprabasin antibodies multiple cytokines chemokines potential predictive biomarkers neuropsychiatric systemic lupus erythematosus neuropsychiatric systemic lupus erythematosus npsle varies presentation one leading causes morbidity mortality among patients sle study determined critical serum biomarkers development npsle may clinical utility prior onset neuropsychiatric symptoms retrospectively analyzed 35 npsle patients 34 sle patients 20 viral meningitis vm patients 16 relapsingremitting multiple sclerosis ms patients,0.0
correction ascertaining medication use patientreported outcomes via app exploring gamification patients multiple sclerosis treated interferon beta1b observational study abstract corrects article doi 102196 31972,0.0
remote administration bicams measures trailmaking test assess cognitive impairment multiple sclerosis reliable remote cognitive testing provide safer assessment cognitive impairment multiple sclerosis ms covid19 pandemic thereafter aimed investigate reliability feasibility administering brief international cognitive assessment ms bicams trailmaking test tmt people ms online betweengroup differences bicams tmt examined sample 68 participants group 1 n 34 tested inperson,0.0
microrna92a promotes cns autoimmunity modulating regulatory inflammatory t cell balance disequilibrium immunosuppressive regulatory t cells tregs inflammatory interleukin il 17producing th17 cells hallmark autoimmune diseases including multiple sclerosis ms however molecular mechanisms underlying treg th17 imbalance central nervous system cns autoimmunity remain largely unclear identifying factors drive imbalance high clinical interest report major diseasepromoting role microrna92a mir92a cns,0.0
association actigraphyderived behavioral clusters selfreported fatigue persons multiple sclerosis crosssectional study conclusions cluster analysis data proved feasible meaningfully differentiate different behavioral syndromes selfreports reflected different behavioral syndromes strongly testing additional domains eg volition processing speed assessments everyday life seem warranted better understand origins reported fatigue symptomatology,0.0
relation sensorimotor cognitive cerebellum functional connectivity brain structural damage patients multiple sclerosis disability abstract objective investigate relation functional connectivity fc sensorimotor cognitive cerebellum measures structural damage patients multiple sclerosis ms physical disability methods selected 144 relapsingremitting ms patients expanded disability status scale score 15 98 healthy controls italian neuroimaging network initiative database multimodal 3t magnetic resonance imaging mri including functional mri rest calculated lesion load cortical thickness white matter cortical gray matter caudate putamen thalamic cerebellar volumes voxelwise fc sensorimotor cognitive cerebellum assessed seedbased analysis multiple regression analysis used evaluate relationship fc structural damage results whole brain white matter caudate putamen thalamic volumes reduced patients compared controls cortical grey matter significantly different patients versus controls sensorimotor cognitive cerebellum showed widespread pattern increased decreased fc negatively associated structural measures indicating lower fc greater tissue loss lastly among multiple structural measures cortical gm wm volumes best predictors cerebellar fc alterations conclusions increased decreased cerebellar fc several brain areas coexist ms patients disability data suggest white matter loss hampers fc absence atrophy cortical volume represents framework fc increase keywords cognitive cerebellum disability functional mri multiples sclerosis neural plasticity sensorimotor cerebellum,0.0
burden illness first year diagnosed bladder dysfunction among people spinal cord injury multiple sclerosis danish register study background people spinal cord injury sci multiple sclerosis ms often living degree bladder bowel dysfunction due acquired neurogenic damage objective estimate burden illness sci ms first year diagnosed bladder dysfunction methods data extracted registers covering danish citizens people sci ms indexed diagnosis bladder dysfunction inclusion period 20022015 cases matched controls followed one year results 2 132 subjects sci 1 887 subjects ms identified healthcare utilization societal costs per patientyear significantly higher cases compared controls driven primarily inpatient care cases urinary tract infection significantly higher inpatient costs per patientyear compared controls sci 544 eur vs 23 p005 ms 497 eur vs 6 p005 medication constipation significantly costly per patientyear sci 178 eur vs 3 p005 ms 78 vs 1 p005 conclusions study demonstrates heavy societal personal costs first year bladder dysfunction people sci ms emphasizes need medical social interventions reduce burden illness keywords cost illness healthcare costs multiple sclerosis neurogenic bladder societal costs spinal cord injury urinary tract infection,0.0
classification multiple sclerosis patients based structural disconnection robust feature selection approach abstract background purpose although structural disconnection represents hallmark multiple sclerosis ms pathophysiology classification attempts based structural connectivity achieved low accuracy levels set fill gap exploring performance supervised classifiers features derived microstructure informed tractography selected applying novel robust approach methods using microstructure informed tractography diffusion mri data created quantitative connectomes 55 ms patients 24 healthy controls used robust approachbased two classical methods feature selection select relevant features three network representations whole connectivity matrices node strength local efficiency classification accuracy selected features tested five different classifiers meaningfulness tested via correlation clinical scales comparison classifiers run features selected standard procedure network analysis thresholding results procedure identified 11 features whole net five local efficiency seven node strength classifiers accuracy range 645911 features extracted whole net reaching maximum overcoming results obtained standard procedure cases correlations clinical scales identified across functional domains motor cognitive abilities fatigue depression conclusion applying robust feature selection procedure quantitative structural connectomes able classify ms patients excellent accuracy providing information white matter connections gray matter regions affected ms pathology keywords classification machine learning microstructure informed tractography multiple sclerosis quantitative structural connectivity robust feature selection,0.0
comparison goals set people multiple sclerosis two fatigue management interventions background identifying meaningful goals people multiple sclerosis pwms can facilitate tailored treatment plans objectives describe compare goals set pwms two interventions explore strategies used meet goals barriers facilitators influencing goal achievement methods data 56 communitydwelling pwms used secondary analysis 45 used interactive fatigue selfmanagement website ms inform 11 received ms inform coupled occupational performance coaching opc 3 months international classification functioning disability health icf used map compare goals strategies facilitators obstacles goal achievement groups goals also evaluated specific measurable attainable relevant timely smart results goals related looking ones health n 35 recreation leisure n 17 participants received opc set smart goals 75 vs 24 p 001 fatigue management strategies identified personal environmental factors found facilitators obstacles goal achievement conclusion significance coaching can help pwms goal setting adapt strategies achieve goals increased awareness goals set pwms may equip clinicians better assess clients needs keywords coaching secondary analysis selfmanagement,0.0
pregnancy fetal infant outcomes following maternal exposure glatiramer acetate pregnancy breastfeeding abstract introduction published data support safety glatiramer acetate patients multiple sclerosis pregnant breastfeeding longterm data limited objective aimed assess pregnancy fetal infant outcomes following maternal exposure glatiramer acetate methods inutero glatiramer acetateexposed postmarketing pregnancy reports 2019 2021 extracted tevas pharmacovigilance database pregnancy data acquired prior knowledge pregnancy outcome detection congenital malformation prospective reports used estimate pregnancy infant outcome rates glatiramer acetate 20 40mg ml exposure subgroup cases completed followup questionnaires analyzed separately results prospective cases 702 fetuses known outcomes 647 922 live births 47 67 spontaneous abortions 4 06 induced abortions 2 03 ectopic pregnancies 2 03 fetal deaths rates major congenital malformation 11 preterm births 72 low low birth weight 48 parameters growth within background rates infant developmental delay reported overall pregnancy infant outcomes similar across glatiramer acetate doses conclusions maternal exposure glatiramer acetate appear related adverse pregnancy fetal infant outcomes data support safety glatiramer acetate 20mg ml 40mg ml treatments pregnancy breastfeeding,0.0
aerobic exercise increases irisin serum levels improves depression fatigue patients relapsing remitting multiple sclerosis randomized controlled trial backgroundmultiple sclerosis ms chronic progressive neurodegenerative disease central nervous system although increasing evidence aerobic exercise positive effect cognitive psychological functioning limited evidence relapsingremitting ms rrms patients moreover unclear exercise modality intensity irisin cleaved circulating form exerciseassociated membrane protein fibronectin type iii domain containing 5 induced patients ms study aimed investigate effect regular aerobic exercise program irisin serum level depression fatigue cognitive performance patients msmethodsthirtytwo individuals rrms randomized 2 groups control study groups mean edss score 169 197 respectively study group received combined exercise training consisting three sessions aerobic exercise frenkel coordination exercises per week 6 weeks control group received frenkel coordination exercise training study cognitive performance participants evaluated paced auditory serial addition test 3second stimulus pasat3 maximum aerobic capacity fitmate pro vo2max fatigue status fatigue impact scale fis depression status beck depression inventory bdi irisin serum levels analyzed enzymelinked immunosorbent assay elisa test serum samples individualsresultsour results revealed irisin serum level significantly increased study group significant improvement aerobic capacity pasat3 fis bdi values observed study group compared control group irisin vo2max fis bdi values groups compared significant difference found favor study groupconclusionthe aerobic exercise revealed significant changes depression fatigue irisin serum levels ms patients think study significant increase irisin serum level significant improvement depression cognitive performance fatigue states obtained study group will pioneering study future studies aiming investigate effects irisin serum level symptoms detail,0.0
microglia phenotypes associated subregional patterns concomitant tau amyloid synuclein pathologies hippocampus patients alzheimers disease dementia lewy bodies abstractthe cellular alterations hippocampus lead memory decline shared symptom alzheimers disease ad dementia lewy bodies dlb patients however subregional deterioration pattern hippocampus differs ad dlb ca1 subfield severely affected ad activation microglia brain immune cells play role selective volume loss subregional microglia populations vary within ad dlb across conditions remains poorly understood furthermore nature hippocampal local pathological imprint associated microglia responses needs elucidated purpose employed automated pipeline analysis 3d confocal microscopy images assess ca1 ca3 dg ca4 subfields microglia responses postmortem hippocampal samples lateonset ad n 10 dlb n 8 agematched control ctl n 11 individuals parallel performed volumetric analyses hyperphosphorylated tau ptau amyloid phosphorylated synuclein psyn loads 32 447 extracted microglia 16 morphological features measured classify seven distinct morphological clusters results show similar alterations microglial morphological features clusters ad dlb prominent changes ad identified two distinct microglia clusters enriched disease conditions particularly increased ca1 dg ca4 ad ca3 dlb study confirms frequent concomitance ptau psyn loads across ad dlb reveals specific subregional pattern type pathology along generally increased severity ad furthermore ptau psyn loads highly correlated across subregions conditions uncovered tight associations microglial changes subfield pathological imprint findings suggest combinations severity subregional ptau psyn pathologies transform local microglia phenotypic composition hippocampus high burdens ptau psyn associated increased microglial alterations factor ca1 vulnerability ad,0.0
clinical prognostic aspects patients neuromyelitis optica spectrum disorder nmosd cohort northeast brazil abstractintroductionneuromyelitis optica spectrum disorders nmosd rare inflammatory demyelinating disease central nervous system cns frequent women afrodescendants previous epidemiological prognostic study conducted region state bahia brazilian northeastobjectiveto evaluate clinical prognostic aspects patients nmosd cohort northeastern brazilmaterial methodsa singlecenter retrospective study conducted consecutive patients diagnosed nmosd clinical epidemiological characteristics described degree disability expressed expanded disability status scale edss worsening disability analyzed negative binomial regression adjusted disease durationresultsninetyone patients included 72 791 female 67 736 afro descendants mean age onset 36 14 years 733 antiaquaporin4 antibody positive isolated transverse myelitis 329 isolated optic neuritis 224 frequent initial clinical syndromes multivariate analysis optic neuritis rr 045 95 ci 023 088 p 0020 dyslipidemia rr 040 95 ci 020 083 p 0014 associated slower disease progression area postrema involvement rr 670 95 ci 331 1354 p 0001 age onset rr 103 95 ci 101 105 p 0003 associated faster disease progressionconclusionsin first clinical prognostic study northeastern brazil identified area postrema involvement age onset optic neuritis fist syndrome dyslipidemia main prognostic factors associated disease progression,1.0
quantifying amount physical rehabilitation received individuals living neurological conditions community scoping review background physical rehabilitation often prescribed immediately following neurological event neurological diagnosis however many individuals require physical rehabilitation hospital discharge purpose scoping review determine amount physical rehabilitation individuals living community neurological conditions receive understand current global practices assess gaps research service usemethodsthis scoping review included observational studies 1 involved adults living neurological condition 2 quantified amount rehabilitation received community outpatient hospital setting literature published english considered medline embase amed cinahl cochrane library pedro databases searched inception two independent reviewers screened titles abstracts followed full texts data extraction mean annual hours rehabilitation estimated based amount rehabilitation reported included studiesresultsoverall 18 studies included screen 14 698 articles estimated mean annual hours rehabilitation varied greatly 49 1551 h individuals spinal cord injury stroke receiving greatest number hours participants typically received physical therapy occupational therapy difference range 1 22 h year lastly one study included individuals progressive neurological conditions highlighting research gapdiscussionthe amount rehabilitation received individuals neurological conditions living community varies greatly wide range time spent rehabilitation likely amount rehabilitation received individuals community insufficient improve function quality life future work identify barriers accessing rehabilitation resources community much rehabilitation needed observe functional improvements,0.0
occult insulinoma treatment refractory severe hypoglycaemia multiple endocrine neoplasia type 1 syndrome difficulties faced diagnosis localization management case report background multiple endocrine neoplasia type 1 men 1 syndrome rare complex genetic disorder characterized increased predisposition tumorigenesis multiple endocrine nonendocrine tissues diagnosis management men 1 syndrome challenging due vast heterogeneity clinical presentationcase presentationa 23yearold female previously diagnosed polycystic ovarian syndrome pcos pituitary microprolactinoma presented drowsiness confusion profuse sweating developing period one day preceded fluctuating hallucinatory behavior two weeks duration recent increase appetite significant weight gain fever seizures symptoms suggestive meningism body mass index bmi 32 kg m2she signs hyperandrogenism multiple cutaneous collagenomas noted anterior chest abdominal wall glasgow coma scale 9 15 pupils sluggishly reactive light tendon reflexes exaggerated going planter reflexes moderate hepatomegaly present rest clinical examination normal laboratory evaluation confirmed endogenous hyperinsulinaemic hypoglycaemia suggestive insulinoma hypercalcemia elevated parathyroid hormone level suggested parathyroid adenoma presence insulinoma primary hyperparathyroidism pituitary microadenoma 3rd decade life characteristic cutaneous tumours suggestive clinical diagnosis men 1 syndrome recurrent severe hypoglycaemia complicated hypoglycaemic encephalopathy refractory continuous parenteral glucose supplementation optimal pharmacotherapy complicated clinical course insulinoma localized selective arterial calcium stimulation test distal pancreatectomy four gland parathyroidectomy performed leading resolution symptomsconclusionsrenal calculi characteristic cutaneous lesions might forewarning clinical manifestations undiagnosed men 1 syndrome impending lifethreatening presentation comprehensive management men 1 syndrome requires multidisciplinary approach advanced imaging modalities advanced surgical procedures longterm follow due heterogeneous presentation varying severity depending disease phenotype,0.0
progressive multifocal fibrosing neuropathy description novel disease abstractentrapment peripheral neuropathies clinically characterized sensory impairment motor deficits usually caused mechanical injuries also frequent manifestation metabolic diseases toxic agent exposure systemic fibrotic disorders describe clinical radiological histopathological features novel progressive fibrotic disorder characterized progressive multifocal fibrosing neuropathy identified two patients presented severe progressive peripheral neuropathic symptoms sequentially affecting multiple sites patients presented severe progressive multifocal sequentially additive peripheral neuropathic symptoms extensive nerve conduction radiological studies showed sequential development multifocal motor sensory peripheral neuropathy absence exposure known infectious inflammatory fibrotic triggers lack family history compression neuropathies extensive clinical laboratory test evaluation failed support diagnosis primary inflammatory genetic peripheral neuropathy evidence systemic fibrosing disorder including systemic sclerosis lacking cutaneous fibrotic changes cardiopulmonary abnormalities clinical course progressive sequential development motor sensory deficits upper lower extremities displaying proximal predominance histopathological study tissues obtained nerve release surgeries showed severe perineural fibrosis marked accumulation thick collagen bundles encroaching peripheral nerves evidence vasculitic inflammatory vascular fibroproliferative lesions suggest clinical findings described represent previously undescribed fibrotic disorder affecting peripheral nerves propose descriptive term progressive multifocal fibrosing neuropathy refer novel disorder despite inherent limitations early description hope contribute identification additional cases,0.0
author response serum neurofilament light association progression natalizumabtreated patients relapsingremitting multiple sclerosis abstract,0.0
reader response serum neurofilament light association progression natalizumabtreated patients relapsingremitting multiple sclerosis abstract,0.0
cutting edge effect diseasemodifying therapies sarscov2 vaccineinduced immune responses multiple sclerosis patients multiple sclerosis ms demyelinating inflammatory disease cns treated diverse diseasemodifying therapies suppress immune system severe acute respiratory syndrome coronavirus 2 mrna vaccines effective immunocompetent individuals whether ms patients treated modifying therapies afforded protection known study determined dimethyl fumarate caused momentary reduction antispike s specific abs cd8 t cell,1.0
editors note serum neurofilament light association progression natalizumabtreated patients relapsingremitting multiple sclerosis abstract,0.0
associations optical coherence tomography disability brain mri volumetry patients multiple sclerosis abstract aim study investigate crosssectional study correlations optical coherence tomography oct clinical magnetic resonance imaging mri parameters multiple sclerosis ms patients material methods oct parameters include peripapillary retinal nerve fibre layer prnfl ganglion cell complex gcc brain magnetic resonance volumetry t2 t1 lesions volume whole brain volume grey matter volume evaluated using icobrain program clinical data compared according history optic neuritis hon correlations determined oct parameters demographic age gender clinical disease duration expanded disability status scale score edss mri data results 83 recruited people ms 27 hon mean age 75 patients nonon eyes 4208 1036 years 7067 sample females significant correlations found prnfl disability along several brain mrivolumetry variables fluidattenuated inversion recovery lesions volume flair t1hypointense lesions volume t1lesions volume change t1volume lesions enlarging whole brain volume whole brain volume normative percentile volume periventricular lesions multivariable linear regression analysis showed age prnfl gcc significantly associated t1hypointense lesions volume change model explained 24 overall variance dependent variable conclusions prfnl value correlates disability brain mrivolumetric parameters ms patients serving useful neurodegeneration inflammation surrogate marker keywords brain magnetic resonance volumetry multiple sclerosis neuroophthalmology optical coherence tomography,0.0
psoriasis pneumonia endstage renal disease population background psoriasis common chronic inflammatory skin disease associated increased risk acute infections chronic kidney disease risk factor pneumonia endstage renal disease esrd patients psoriasis may increased risk acquiring pneumonia methods retrospective cohort analysis performed using united states renal data system medical claims database esrd patients undergoing dialysis us logistic regression analysis used investigate association psoriasis pneumonia esrd patients results total 6 841 07 esrd patients diagnosed psoriasis 385 976 36 esrd patients pneumonia although simple models showed psoriasis associated increased risk pneumonia esrd population odds ratio 114 final multivariable model found psoriasis protective pneumonia 056 controlling age race sex ethnicity dialysis modality charlson comorbidity index cci multiple sclerosis tobacco use alcohol use due cci tobacco use strong confounders association psoriasis pneumonia black race hispanic ethnicity also protective pneumonia increasing age cci female sex hemodialysis multiple sclerosis tobacco alcohol use associated increased risk conclusions controlling multiple factors psoriasis increase risk pneumonia esrd patients cohort factors cci tobacco use strongly associated increased risk pneumonia psoriasis keywords chronic kidney disease pneumonia psoriasis,0.0
protecting effect emodin experimental autoimmune encephalomyelitis mice inhibiting microglia activation inflammation via myd88 pi3k akt nfb signalling pathway experimental autoimmune encephalomyelitis eae characterised demyelination central nervous system emodin anthraquinone derivative comprehensive antiinflammatory anticancer immunomodulatory effects widely used treatment inflammatory tumour immune system diseases however none clinical experimental studies explored therapeutic efficacy emodin eae multiple sclerosis ms thus evaluated protective effect,1.0
antibody therapies progressive multiple sclerosis promoting repair progressive multiple sclerosis pms clinically distinct relapsingremitting ms rrms pms clinical disability progression occurs independently relapse activity furthermore increasing evidence pathological mechanisms pms rrms different current therapeutic options treatment pms remain inadequate although ocrelizumab bcelldepleting antibody now available first approved therapeutic option primary progressive ms recent,0.0
neuromotor control associates muscle weakness observed mcardle sign multiple sclerosis objective multiple sclerosis ms often accompanied myelopathy may associated progressive worsening specific finding msassociated myelopathy mcardle sign wherein neck flexion associated prominent increased limb weakness relative detected neck extension study characterized neuromotor control properties finger extensors association mcardle sign,0.0
transdermal delivery baclofen using iontophoresis microneedles baclofen gaba b agonist used treatment multiple sclerosis neurodegenerative disease currently available dosage forms deliver baclofen oral intrathecal routes disadvantage oral baclofen requires administering drug multiple times day owing baclofens short halflife hand intrathecal baclofen pumps invasive alternative oral baclofen hence need develop dosage form,0.0
overground robotic training effects walking secondary health conditions individuals spinal cord injury systematic review abstractoverground powered lower limb exoskeletons exos proven valid devices gait rehabilitation individuals spinal cord injury sci although several articles reported effects exos individuals reviews available focused specific domains mainly walking aim systematic review provide general overview effects commercial exos ie exos used military industry applications medical purposes individuals sci systematic review conducted following prisma guidelines referred medline embase scopus web science cochrane library databases studies included randomized clinical trials rcts nonrct based exos intervention individuals sci 1296 studies screened 41 met inclusion criteria among exo studies ekso device discussed followed rewalk indego hal rex devices since 14 different domains considered outcome measures heterogeneous investigated domain walking followed cardiorespiratory metabolic responses spasticity balance quality life humanrobot interaction robot data bowel functionality strength daily living activity neurophysiology sensory function bladder functionality body composition bone density domains reports negative effects due exos trainings significant positive effects noted walking domain ekso rewalk hal indego devices ekso studies reported significant effects due training almost domains case rex device single study carried sensory functions bladder functionality reached significance exo possible draw general conclusions effects exos usage due lack highquality studies addressed downs black tool heterogeneity outcome measures protocols sci epidemiological neurological features however strengths weaknesses exos starting defined even considering different types adverse events exo training brought exo training showed bring significant improvements time whether effectiveness greater less conventional therapy treatments still mostly unknown highquality rcts necessary better define pros cons exos available today studies kind help clinicians better choose appropriate training individuals sci,0.0
immunotactoid glomerulopathy enigmatic case setting nodal marginal zone lymphoma systemic sclerosis sine scleroderma background immunotactoid glomerulopathy itg exceedingly rare type glomerulopathy characterised distinctive electron microscopic features itg linked lymphoproliferative autoimmune disorders clinical manifestations diverse including nephrotic syndrome ns haematuria acute kidney injury end stage renal failure esrd present case stage 3 nodal marginal zone lymphoma nmzl systemic sclerosis sine scleroderma ssss evolution itg documented 2 renal biopsies 19 months apart best knowledge cases reported linking itg nmzl furthermore one nonpeer reviewed report linking itg scleroderma discuss implications findings highlight satisfactory management casecase presentationa 79yearold female history systemic sclerosis sine scleroderma stage 3 nmzl presented acute kidney injury ns background chronic kidney disease first kidney biopsy showed diffuse proliferative glomerulonephritis serum protein electrophoresis showed abnormalities managed satisfactorily conservative measures returned 19 months later features fluid overload increasing proteinuria rising serum creatinine repeat serum protein electrophoresis showed excess free kappa light chains itg detected repeat kidney biopsy kidney function proteinuria showed good sustained response rituximab administered second biopsyconclusionitg rare type glomerulopathy associated underlying haematological malignancies autoimmune disorders may result esrdrituximab one effective agents used management itg haematological malignancies,0.0
impaired glymphatic function early stages disease tdp43 mouse model amyotrophic lateral sclerosis background multiple lines evidence suggest possible impairment glymphatic system amyotrophic lateral sclerosis als investigate used vivo magnetic resonance imaging mri assess glymphatic function early course disease transgenic mouse doxycycline dox controlled expression cytoplasmic human tdp43 htdp43nls mimicking key pathology implicated alsmethodsadult tdp43 transgenic littermate monogenic control mice underwent longitudinal multimodal mri one three weeks cessation dox feed together weekly rotarod assessments motor performance glymphatic function assessed using dynamic contrastenhanced mri track clearance mr contrast agent injected cisterna magnaresultscompared littermate controls tdp43 mice exhibited progressive neurodegeneration including within primary motor cortex primary somatosensory cortex corticospinal tract significant weight loss including gastrocnemius atrophy shortened telomere length furthermore presence alslike phenotype mice significantly disrupted glymphatic functionconclusionsalthough relationship glymphatic clearance als disease progression remains elucidated changes occurred early disease course provides initial evidence suggest glymphatic system might potential therapeutic target treatment als,0.0
prevalence thoracoabdominal imaging findings tuberous sclerosis complex background tuberous sclerosis complex tsc results neurodevelopmental phenotypes benign tumors cysts throughout body recent studies show numerous rare findings tsc guidelines suggest routine abdominal chest imaging monitor thoracoabdominal findings imaging uniformly done across centers thus prevalence many findings unknown answer categorized clinical reads 1398 thoracoabdominal scans 649 patients ages cincinnati childrens hospital tsc repository databaseresultstypical tsc findings present many patients kidney cysts 72 kidney fatcontaining angiomyolipomas 51 kidney lipidpoor angiomyolipomas 27 liver angiomyolipomas 19 lung nodules thought represent multifocal micronodular pneumocyte hyperplasia mmph 18 many features common tsc2 patients tsc1 patients higher prevalence mmph tsc2 patients 24 versus 13 p 005 many rare findings eg lymphatic malformations liver masses common tsc general population additionally thoracoabdominal imaging findings increased age except kidney cysts decreased 010 years age group highest percentage 69 010 years 49 1021 years 48 21 + years p 0001 finally population patients renal cell carcinoma found abdominal imagingconclusionsthese results show regular thoracoabdominal scans tsc may show several findings ignored conversely overreacted found patients tsc female sex tsc2 mutation age risk factors many thoracoabdominal findings data suggest novel interactions genetic mutation pulmonary nodules age renal cysts finally agreement works findings indicate several rare thoracoabdominal imaging findings occur higher rates tsc population general population work supports obtaining detailed thoracoabdominal imaging patients tsc,0.0
changes cannabis use associated correlates frances first covid19 lockdown daily cannabis users results large communitybased online survey background lockdown measures first wave covid19 pandemic france led serious public health concerns people use illicit drugs especially terms mental health assessed changes cannabis use first lockdown france among daily cannabis users associated correlates methodscannavid french national crosssectional webbased survey conducted 17 april 11 may 2020 daily cannabis users aged 18 years living france invited participate advertisements respondents completed ad hoc questionnaire dedicated online platform analyzed changes cannabis use first lockdown ie stopped decreased unchanged increased performed multinomial logistic regression analysis evaluate correlates changesresultsof 4019 participants 740 men median age 27 years interquartile range 2237 regard cannabis use 293 73 persons stopped 1153 287 decreased 1146 285 change 1427 355 increased use lockdown multinomial logistic regression model revealed several sociodemographic behavioral healthrelated factors associated changes cannabis use compared participants unchanged level cannabis use lockdown increased stopped cannabis use likely increased tobacco alcohol use experienced depression sleep disorders intensification stopped cannabis use also likely increased benzodiazepine use experienced pain increase lockdownconclusionsfrances first covid19related lockdown differential impact daily cannabis users consumption patterns study respondents reported changes cannabis consumption pattern reported stable cannabis use likely report fewer negative changes specific interventions needed population well research assess longterm impacts changes,0.0
therapeutic effect mechanism acupuncture autoimmune diseases autoimmune diseases aids conditions arising abnormal immune reactions autoantigens can defined loss immune tolerance autoantigens causing production autoantibodies subsequent inflammation tissue injury etiology aids remains elusive may involve genetic environmental factors diet drugs infections despite rapid progress treatment autoimmune diseases past decades still,0.0
handedness cognition multiple sclerosis potential indications hemispheric vulnerability background multiple sclerosis ms affects 25 million individuals worldwide yet much disease course unknown hemispheric vulnerability ms may elucidate part process yet studied current study assessed neuropsychological functioning relates hemispheric vulnerability ms methods verbal iq measured verbal comprehension index vci nonverbal iq measured perceptual reasoning index pri memory acquisition compared righthanded dextral nonrighthanded nondextral persons ms pwms results linear mixedeffects modeling indicated significant main effect handedness f 1 19535 395 p 048 composite measure vci pri memory acquisition better performance dextral pwms examining differences specific neuropsychological measures largest effect size dextral nondextral participants seen pri d 0643 f 1 341 12163 p 001 significant interaction effect handedness iq found f 3 52560 075 p 523 conclusions dextral pwms perform better nondextral pwms assessing neuropsychological performance memory iq combined results suggestive increased vulnerability left brain pathological process ms keywords assessment epilepsy intelligence language language disorders lateralization multiple sclerosis,0.0
distinct gene expression demyelinated white grey matter areas patients multiple sclerosis demyelination central nervous system prominent pathological hallmark multiple sclerosis affects white grey matter however demyelinated white grey matter exhibit clear pathological differences notably presence absence inflammation activated glial cells white grey matter respectively order gain insight differential pathology demyelinated white grey matter areas microdissected neighbouring white grey,1.0
realworld effectiveness safety profile teriflunomide management multiple sclerosis gulf cooperation council countries expert consensus narrative review background prevalence multiple sclerosis ms increasing gulf cooperation council gcc countries multiple sclerosis contributes significant burden patients caregivers pharmacological treatment ms involves treating acute exacerbations preventing relapses disability progression using diseasemodifying therapies clinical evidence suggests teriflunomide one therapeutic choices patients relapsingremitting ms rrms however genetic cultural differences across different regions may contribute variations drug use therefore necessary consider realworld evidence teriflunomide usage gcc countries methods expert group ms gathered gcc countries december 2020 consensus highlighting role teriflunomide ms management developed using clinical experiences evidencebased approach results expertrecommended patient profile teriflunomide usage includes individuals aged 18 years men women effective contraceptives clinically isolated syndrome rrms factors considered costeffectiveness drug patient preference adherence monitoring established safety profile coronavirus disease 2019 status conclusion expert recommendations based clinical experience will helpful clinicians clinical settings regarding usage teriflunomide provide valuable insights applicable daytoday practice keywords diseasemodifying therapies multiple sclerosis realworld evidence relapse teriflunomide,0.0
stratification multiple sclerosis patients using unsupervised machine learning singlevisit mridriven approach abstract objectives stratify patients multiple sclerosis pwms based brain mriderived volumetric features using unsupervised machine learning methods 3t brain mris relapsingremitting pwms including 3dt1w flairt2w sequences retrospectively collected along expanded disability status scale edss scores longterm 10 2 years clinical outcomes edss cognition progressive course mris volumes demyelinating lesions 116 atlasdefined gray matter regions automatically segmented expressed zscores referenced external populations following feature selection baseline mriderived biomarkers entered subtype stage inference sustain algorithm estimates subgroups characterized distinct patterns biomarker evolution stages within subgroups trained model applied longitudinal mris stability subtypes stage change time assessed via krippendorfs multilevel linear regression models respectively prognostic relevance sustain classification assessed ordinal logistic regression analyses results selected 425 pwms 359 99 years f m 301 124 corresponding 1129 mri scans along healthy controls n 148 359 130 years f m 77 71 external pwms n 80 404 119 years f m 56 24 reference populations based 11 biomarkers surviving feature selection two subtypes identified designated deep gray matter dgm first subtype n 238 cortexfirst subtype n 187 according atrophy pattern subtypes consistent time 0806 significant annual stage increase b 020 p 0001 edss associated stage dgmfirst subtype p 002 baseline stage predicted longterm disability transition progressive course cognitive impairment p 003 latter also associated dgmfirst subtype p 0005 conclusions unsupervised learning modelling brain mriderived volumetric features provides biologically reliable prognostically meaningful stratification pwms key points unsupervised modelling brain mriderived volumetric features can provide singlevisit stratification multiple sclerosis patients soobtained classification tends consistent time captures diseaserelated brain damage progression supporting biological reliability model baseline stratification predicts longterm clinical disability cognition transition secondary progressive course keywords brain machine learning magnetic resonance imaging multiple sclerosis prognosis,1.0
targeting lipophagy macrophages improves repair multiple sclerosis foamy macrophages containing abundant intracellular myelin remnants important pathological hallmark multiple sclerosis reducing intracellular lipid burden foamy macrophages considered promising therapeutic strategy induce phagocyte phenotype promotes central nervous system repair recent research group showed sustained intracellular accumulation myelinderived lipids skews phagocytes toward diseasepromoting inflammatory,1.0
pregnancy outcome following exposure ocrelizumab multiple sclerosis background ocrelizumab monoclonal antibody targeting cd20expressing b cells used treatment multiple sclerosis ms currently limited safety data pregnancy objectives report pregnancy outcome following exposure ocrelizumab ms methods retrospectively identified 14 pregnancies 12 ms patients exposed ocrelizumab within 6 months prior conception pregnancy specialty clinic western australia results 13 14 pregnancies resulted live births one pregnancy electively terminated following detection chromosomal defect one pregnancy complicated placental insufficiency infant developed hyaline membrane disease complicated sepsis observed major congenital anomalies preterm births stillbirths low birthweight observe serious maternal infections patients relapsefree despite mean ocrelizumabfree interval 651 weeks conclusions identify major safety signals among patients received ocrelizumab prior conception first trimester pregnancy patients appeared stable disease course despite prolonged period treatment interruption pregnancy keywords multiple sclerosis anticd20 therapy ocrelizumab pregnancy outcome,0.0
ermin deficiency leads compromised myelin inflammatory milieu susceptibility demyelinating insult ermin actinbinding protein found almost exclusively central nervous system cns component myelin sheaths although ermin predicted play role formation stability myelin sheaths directly examined vivo show ermin essential myelin sheath integrity normal saltatory conduction loss ermin mice caused decompacted fragmented myelin sheaths led slower conduction along progressive,1.0
decreasing multiple sclerosis treatment expenditures improving quality health system level abstract objective evaluate multicomponent health system intervention designed reduce escalating diseasemodifying treatment dmt expenditures improve multiple sclerosis ms outcomes increasing use preferred formulary highly effective dmts het methods conducted trend study treatment utilization expenditure outcomes prior 20092011 20122018 ms treatment optimization program mstop implementation kaiser permanente southern california kpsc compared kp region similar size annual relapse rates arr obtained kpscs electronic health records results adherence preferred formulary dmts increased 254 2011 722 2017 following mstop implementation kpsc 221 438 respectively comparator kpscs annual dmt expenditures 2018 less 2011 despite 113 increase dmttreated members decline average perpatientperyear treatment expenditures peak 431k 2014 263k 2018 kspc greater comparator peaked 521k declined 400k 2018 7 years following initiation mstop cumulative ms dmt expenditures 1616 million less comparator het use increased 625 perpatienttreatmentyears versus 324 comparator corresponded 69 decline adjusted arr 95ci 641732 p00001 among dmttreated patients kpsc interpretation novel expertled health system intervention reduced ms dmt expenditures despite rising prices simultaneously reducing ms relapse rates focus health system progress toward meaningful measurable targets serve model improve quality affordability ms care settings article protected copyright rights reserved,0.0
olfactory threshold predicts treatment response relapsing multiple sclerosis background olfactory threshold ot associated shortterm inflammatory activity relapsing multiple sclerosis rms objective aimed investigate ot prediction treatment response rms methods 5year prospective study 123 rms patients ot measured diseasemodifying treatment dmt initiation m0 3 months m3 12 months m12 sniffin sticks test primary endpoint defined absence relapse observation period expanded disability status scale edss progression magnetic resonance imaging mri activity secondary endpoints optimal cutoff values determined receiver operating characteristic analyses predictive value assessed multivariable cox regression models results higher ot scores m0 m3 m12 independently associated decreased relapse probability strongest risk reduction m3 hazard ratio hr 044 p 0001 improvement ot scores m0 m3 otm3 also associated reduced relapse risk hr 012 p 0001 ot score 65 m3 strongest predictor relapse freedom hr 010 p 0001 high diagnostic accuracy positive predictive value ppv 87 closely followed otm3 05 hr 012 p 0001 ppv 86 conclusions ot independent predictor freedom disease activity upon dmt initiation within 5 years may useful biomarker treatment response keywords mri multiple sclerosis diseasemodifying treatment olfactory threshold relapse treatment response,0.0
response sarscov2 vaccination multiple sclerosis patients disease modifying therapies abstract,0.0
ascertaining medication use patientreported outcomes via app exploring gamification patients multiple sclerosis treated interferon beta1b observational study background betaconnect autoinjector mybetaapp app designed support patients multiple sclerosis receiving interferon 1b ideal platform digital observational studies recent pilot study germany demonstrated feasibility using app recruit patients obtain informed consent evaluate medicationtaking behavior 6 months objective study aims describe medicationtaking behavior 1 year patients multiple sclerosis receiving interferon 1b based data collected app provide information patientreported outcomes pros optional use cognitive training tool peak peak formerly brainbow ltd included test feasibility gamification setting methods prospective retrospective exploratory digital observational cohort study conducted among users app germany invitations participate sent patients apps february may 2019 participants provided electronic informed consent injectionrelated data consenting patients devices collected prospectively 1 year following consent date retrospectively 1 year first day use historical data available participants also completed three electronic pro instruments every 3 months euroqol 5dimension 5level questionnaire eq5d5l treatment satisfaction questionnaire medication tsqm version ii questionnaire satisfaction treatment support server accessed via emailed hyperlink patients offered optional access professional version peak results 1778 registered app accounts may 2019 79 patients 444 provided informed consent 62 349 eligible inclusion prospective analysis 60 97 also retrospective data mean age 62 participants 432 sd 115 years 41 66 women compliance 1year prospective observational period primary end point high median 989 iqr 943100 similar among men women persistence adherence coprimary end points decreased 85 53 62 74 46 62 respectively 6 months 76 47 62 65 40 62 respectively 12 months higher men women retrospective analysis showed similar patterns pro questionnaires answered 79 49 62 participants baseline 50 31 62 month 12 women severe problems eq5d5l dimensions mobility usual activities pain discomfort lower median convenience scores tsqm version ii men month 12 84 26 31 patients satisfied satisfied app peak used 67 14 21 men 49 20 41 women conclusions study showed high compliance decreasing persistence adherence 1 year demonstrated feasibility including remotely completed electronic pro instruments digital observational studies keywords betaconnect app digital observational study gamification healthrelated quality life interferon 1b medication adherence medication compliance medication persistence mobile phone multiple sclerosis,0.0
diagnostic imaging diagnostics multiple sclerosis multiple sclerosis ms inflammatory autoimmune disease leads development demyelination foci central nervous system can affect neurological function developed world represents common chronic neurological nontraumatic disease young middleaged patients magnetic resonance imaging mri firstline imaging modality diagnosis followup ms currently valid mcdonald criteria updated 2017 define exact,1.0
covid19 outcomes vaccination people relapsing multiple sclerosis treated ofatumumab abstract introduction sarscov2 pandemic necessitated better understanding impact diseasemodifying therapies covid19 outcomes vaccination report characteristics covid19 cases vaccination status ofatumumabtreated relapsing multiple sclerosis rms patients methods covid19 data analyzed ongoing openlabel longterm extension phase 3b alithios study december 2019 pandemic start postmarketing cases august 2020 ofatumumab first approval 25 september 2021 covid19 cases severity seriousness outcomes vaccination status breakthrough infection evaluated results 25 september 2021 245 1703 patients 143 enrolled alithios receiving ofatumumab median exposure 245 years reported covid19 confirmed 210 suspected 35 covid19 mild 441 moderate 465 severity 9 severe lifethreatening covid19 24 serious cases 98 23 patients hospitalized 22 recovered 2 died study cutoff 241 patients 984 recovered recovering recovered sequelae 2 08 recovered ofatumumab temporarily interrupted 39 159 patients covid19 onset igg levels within normal range covid19affected patients igm 04 g l 23 94 patients patient reinfection overall 559 patients vaccinated full 476 partial 74 unspecified 9 breakthrough infection reported 15 7 476 patients 11 reported covid19 partial vaccination 25 september 2021 novartis safety database 4713 patienttreatment years recorded 90 confirmed covid19 cases receiving ofatumumab cases nonserious n 80 ten serious 1 medically significant 9 hospitalized 0 deaths among 36 90 cases outcomes reported 30 recovered 6 recover conclusion covid19 rms patients ofatumumab primarily mild moderate severity nonserious observational data recovered covid19 without treatment interruption two people died covid19 breakthrough covid19 despite fully partially vaccinated uncommon keywords alithios anticd20 therapy bcell therapy covid19 ofatumumab postmarketing relapsing multiple sclerosis sarscov2 vaccination,0.0
fever unknown origin workup diagnosis pelebstein fever clinical diagnostic workup fever unknown origin fuo key treatment patients internal medicine service article authors present case fever unknown origin walk differential diagnosis explain laboratory testing ordered workup patient well resulting values said testing discuss pathophysiology diagnostic criteria diagnosis pelebstein fever authors also discuss clinical,0.0
immunogenetics systemic sclerosis systemic sclerosis ssc rare disease prevalence ranging 7 700 cases per million like autoimmune diseases environmental genetic factors involved pathogenesis ssc though incidence ssc family members affected concordance rate twins low inheritance still strongest risk factor ssc thus multiple studies conducted identify genes responsible inheritance including,0.0
antisense therapies neurological diseases advances targeted regulation gene expression allowed new therapeutic approaches monogenic neurological diseases molecular diagnosis paved way personalized medicine targeting pathogenic roots dna rna transcript antisense therapies rely modified nucleotides sequences singlestrand dna rna belonging antisense oligonucleotides family doublestrand interfering rna act specifically pathogenic target nucleic acids thanks,0.0
dynamics relapses treatment switch relapsingremitting multiple sclerosis based reported trends relapse incidence among patients relapsingremitting multiple sclerosis original model response disease modifying therapies proposed population approach separate states patients accounting risk relapses system nonlinear equations formulated similarly established epidemiological models different parameters describe effect drugs treatment switch reducing frequency relapses model,0.0
serum neurofilament lightchain levels children monophasic myelin oligodendrocyte glycoproteinassociated disease multiple sclerosis acquired demyelinating syndrome abstract objective assess diagnostic prognostic potential serum neurofilament light chain snfl children first acquired demyelinating syndrome ads methods selected 129 children first ads including 19 children myelin oligodendrocyte glycoprotein mog antibody associated disease mogad 36 mog aqp4seronegative ads 74 multiple sclerosis ms biomarker study cohort children complete set clinical radiological laboratory data serum nfl measurement using highly sensitive digital elisa simoa control group 35 children noninflammatory neurological diseases included snfl levels compared across patient groups according clinical laboratory neuroradiological features outcome 2 years results snfl levels significantly increased mogad seronegative ads ms compared controls pvalue 0001 particular children acute disseminated encephalomyelitis adem like magnetic resonance imaging mri pattern p 0001 longitudinally extensive myelitis p 001 pediatric ms elevated snfl levels significantly associated higher numbers cerebral p 0001 presence spinal p 005 mri lesions baseline predicted higher number relapses p 005 conclusion snfl levels significantly elevated three studied pediatric ads subtypes indicating neuroaxonal injury pediatric ms high levels snfl associated risk factors disease progression keywords ads mog ms neurofilament autoimmune children,1.0
response evidence association polygenic risk multiple sclerosis mri phenotypes approximately 30 000 healthy adult uk biobank participants abstract,0.0
mechanistic contributions kupffer cells liver sinusoidal endothelial cells nanoparticleinduced antigenspecific immune tolerance intravenous delivery diseaserelevant antigens ag polymeric nanoparticles npags demonstrated agspecific immune tolerance autoimmune allergic disorders well allogeneic transplant rejection npags observed distribute spleen established role induction immune tolerance however studies shown spleen dispensable npaginduced tolerance suggesting significant contributions immunological sites,0.0
lateral interbody release fused vertebrae via transpsoas approach adult spinal deformity surgery preliminary report radiographic clinical outcomes background lateral interbody release lir via transpsoas lateral approach surgical strategy address degenerative lumbar scoliosis dls patients anterior autofusion vertebral segments study aimed characterize clinical radiographic outcomes lumbar reconstruction strategy using lir achieve anterior column correctionmethodsdata 21 fused vertebrae 17 consecutive patients underwent lir january 2014 march 2020 reviewed demographic intraoperative data recorded radiographic parameters assessed preoperatively final followup including segmental lordotic angle sla segmental coronal angle sca bone union rate pelvic incidence pi lumbar lordosis ll pelvic tilt sacral slope pill mismatch sagittal vertical axis cobb angle deviation c7 plumb line central sacral vertical line clinical outcomes evaluated using oswestry disability index odi visual analog scale vas scores low back leg pain short form 36 health survey questionnaire sf36 postoperatively final followup complications also assessedresultsmean patient age 703 48 years patients female average followup period 284 153 months average procedural time perform lir 213 97 min significantly different traditional lateral interbody fusion levels blood loss per single segment lir 387 532 ml fusion rate 1000 cohort sla improved significantly 76 92 degrees preoperatively 70 88 degrees final observation sca improved significantly 191 78 degrees preoperatively 87 59 degrees final observation p 00001 00001 respectively spinopelvic coronal parameters well odi vas improved significantly incidence peri postoperative complications iliopsoas muscle weakness leg numbness patients underwent lir much xlif incidence postoperative mechanical failure following lir also similar xlif reoperation rate 118 however reoperations associated lir segmentsconclusionsthe lir technique anterior column realignment fused vertebrae context severe asd may option safe effective surgical strategy,0.0
structural visual metrics associate moderate vigorous physical activity youth pediatric onset neuroinflammatory disorders backgroundhigher levels moderate vigorous physical activity mvpa associate disease activity pediatric multiple sclerosis ms measures retinal integrity associate lower brain atrophy yet relationship retinal integrity mvpa investigatedobjectiveto determine relationship mvpa retinal nerve fibre layer rnfl ganglion cellinner plexiform layer gcipl thickness patients ms myelin oligodendrocyte glycoproteinassociated disorders mogad neuromyelitis optica spectrum disorder nmosd monophasic acquired demyelinating syndromes monoads methods150 consecutive children 18 yo neuroinflammatory disorders included outcomes included godin leisure time activity questionnaire glteq modeled continuous categorical variable vs mvpa strenuous activity rnfl gcipl using linear mixed models jasp 0141 resultsan association identified mvpa rnfl thickness f 1 133 840 p 004 gcipl thickness f 1 131 768 p 006 ms cohort strenuous physical activity associated greater rnfl f 1 35 730 p 011 gcipl thickness f 1 35 873 p 006 conclusionsany mvpa participation associated higher rnfl gcipl thickness across neuroinflammatory disorders,1.0
frailty assessment using novel approach based combined motor cardiac functions pilot study background previous research showed association frailty impaired autonomic nervous system however direct effect frailty heart rate hr behavior physical activity unclear purpose current study determine association hr increase decrease frailty localized upperextremity function uef task establish multimodal frailty testmethodsolder adults aged 65 older recruited performed uef task rapid elbow flexion 20 s right arm wearable gyroscopes used measure forearm upperarm motion electrocardiography recorded using leads left chest using setup hr dynamics measured including time peak hr recovery time percentage increase hr uef percentage decrease hr recovery uefresultsfiftysix eligible participants recruited including 12 nonfrail age 7692 732 years 40 prefrail age 8053 812 years four frail individuals age 8825 443 years analysis variance models showed percentage increase hr uef percentage decrease hr recovery 47 smaller prefrail frail older adults compared nonfrails p 001 effect size 070 062 increase decrease percentages using logistic models uef kinematics hr parameters independent variables frailty predicted sensitivity 082 specificity 083conclusioncurrent findings showed evidence strong association hr dynamics frailty suggested combining kinematics hr data multimodal model may provide promising objective tool frailty assessment,0.0
subjective health status easily available independent robust significant predictive factor prometaphase vaccination programs vaccination behavior chinese adults background world health organization proposed covid19 vaccination emergent important method end covid19 pandemic since china started vaccination programs december 2020 vaccination spread provinces municipalities nationwide previous research focused peoples vaccination willingness influencing factors examined vaccination behavior examine effectiveness psychosocial factors predicting vaccination behaviormethodsa crosssectional online survey performed among chinese adults 8 may 4 june 2021 statistical analysis data included univariate analysis receiver operator characteristics roc analysis ordinal multiclassification logistic regression model analysisresultsof 1300 respondents 761 585 vaccinated univariate analysis showed high education level good subjective health status protective factors vaccination behavior suffering chronic diseases risk factor roc analysis showed subjective health status auc 0625 95 ci 05940656 p 0001 best predictor vaccination behavior logistic regression analysis subjective health status dependent variable indicated older age female sex depression neurasthenia obsession hypochondriasis chronic disease significant risk factors positive coping tendencies significant protective factorconclusionour study found simple effective marker subjective health status can predict vaccination behavior finding can guide future epidemic prevention work,0.0
cannabinoids management behavioral psychological motor symptoms neurocognitive disorders mixed studies systematic review abstractaimwe undertook systematic review determine efficacy safety cannabisbased medicine treatment behavioral psychological motor symptoms associated neurocognitive disordersmethodswe conducted prismaguided systematic review identify studies using cannabisbased medicine treat behavioral psychological motor symptoms among individuals alzheimers disease ad dementia parkinsons disease pd huntingtons disease hd considered englishlanguage articles providing original data three participants regardless designfindingswe identified 25 studies spanning 1991 2021 comprised 14 controlled trials 5 pilot studies 5 observational studies 1 case series cases cannabinoids tested dronabinol whole cannabis cannabidiol diagnoses included ad n 11 pd n 11 hd n 3 primary outcomes motor symptoms eg dyskinesia sleep disturbance cognition balance body weight occurrence treatmentemergent adverse eventsconclusionsa narrative summary findings limited number studies area highlights apparent association cannabidiolbased products relief motor symptoms hd pd apparent association synthetic cannabinoids relief behavioral psychological symptoms dementia across ad pd hd preliminary conclusions guide using plantbased versus synthetic cannabinoids safe alternative treatments managing neuropsychiatric symptoms neurocognitive vulnerable patient populations,0.0
promising role temelimab multiple sclerosis treatment backgroundmultiple sclerosis ms chronic debilitating neurological disease affecting young adults disease involves immunemediated demyelination nerve fibers neurons leads disruption brainbody communication leading permanent nerve damage msassociated retrovirus envelope protein msrvenv detected blood lesions ms patients role suggested pathogenesis ms temelimab humanized igg4 monoclonal antibody mab targets msrvenv protein neutralizes action several clinical trials conducted evaluate effectiveness drug msmaterials methodsa systemic search conducted electronic databases pubmed medline cochrane library google scholar inception 11th sept 2021 statistical analysis conducted review manager 541 studies meeting inclusion criteria selected studies selected compared temelimab therapy inactive control primary outcome interest drug safety efficacy information immunogenicity also included randomeffect model used pool studies result reported risk ratio rr corresponding 95 confidence interval ci resultsphase phase iia phase iib trials demonstrate safety effectiveness temelimab analysis showed statistically nonsignificant risk ratio rr adverse events temelimab group placebo group 101 070 146 pvalue 094 i2 0 considering effect temelimab brain lesions pooled result showed statistically significant risk ratio rr brain lesions placebo group temelimab group 075 069 081 pvalue 000001 i2 0conclusionqualitative quantitative analysis trials assessing safety efficacy temelimab demonstrate drug safe well favourable use ms patients,1.0
salivary bacterial signatures depressionobesity comorbidity associated neurotransmitters neuroactive dipeptides background depression obesity highly prevalent often cooccurring conditions marked inflammation microbiome perturbations implicated obesityinflammationdepression interrelationships microbiome mechanistically contributes pathology remains unclear metabolomic investigations microbial neuroactive metabolites may offer mechanistic insights hostmicrobe interactions using 16s sequencing untargeted mass spectrometry saliva blood monocyte inflammation regulation assays identified key microbes metabolites host inflammation association depressive symptomatology obesity depressive symptomatologyobesity comorbidityresultsgramnegative bacteria inflammation potential enriched relative grampositive bacteria comorbid obesitydepression supporting inflammationoral microbiome link obesitydepression interrelationships oral microbiome highly predictive depressive symptomatologyobesity cooccurrences obesity depressive symptomatology independently suggesting specific microbial signatures associated obesitydepression cooccurrences mass spectrometry analysis revealed significant changes levels signaling molecules microbiota microbial dietary derived signaling peptides aromatic amino acids among depressive symptomatology obesity comorbid obesitydepression furthermore integration microbiome metabolomics data revealed key oral microbes many previously shown neuroactive potential cooccurred potential neuropeptides biosynthetic precursors neurotransmitters dopamine epinephrine serotoninconclusionstogether findings offer novel insights oral microbialbrain connection potential neuroactive metabolites involved,0.0
longitudinal assessment relationship visual evoked potentials cognitive performance multiple sclerosis abstract objective visual evoked potentials veps can provide insight disease activity people multiple sclerosis pwms however studies tracked concurrent changes veps cognitive functioning time ms address examined longitudinal relationship vep cognitive performance pwms twoyear period methods baseline t1 followup t2 214 years baseline average p100 peak latency interocular latency iol eyes calculated vep elicited checkerboard patternreversal stimuli cognitive performance assessed seven different domains neurotrax battery potential vep variables predict t1tot2 change cognitive performance assessed series multiple linear regression models results baseline iol vep latency significantly associated t1tot2 change information processing speed posthoc analyses indicated pwms prolonged vep latency elevated iol baseline tended exhibit greater information processing speed decline increase vep latency t1tot2 also associated decline psychomotor function time conclusions findings provide evidence vep measures can serve valuable prognostic indicators longitudinal cognitive change pwms significance visual system neurophysiology corresponds changes speeded cognitive performance ms keywords cognitive decline interocular latency multiple sclerosis p100 psychomotor speed visual evoked potentials,0.0
restless legs syndrome patients multiple sclerosis evaluation risk factors clinical impact abstract introduction restless legs syndrome rls disorder characterised irresistible urge move legs usually accompanied unpleasant sensations frequent patients multiple sclerosis ms general population objectives evaluate prevalence rls defined according 4 essential requirements included diagnostic criteria proposed international restless leg syndrome study group cohort patients ms identify potential risk factors clinical impact rls results sample included 120 patients ms mean age symptom onset 40 years average disease duration 46 months prevalence rate rls 233 ms progression time significantly shorter patients rls p001 recent relapse symptoms anxiety depression neuropathic pain significantly associated risk rls p001 p001 p001 p001 respectively addition patients rls greater risk poor sleep quality fatigue daytime sleepiness poor quality life without rls p002 p017 p013 p009 respectively conclusions rls considered neurological evaluation patients ms early diagnosis treatment improve quality life patients ms presenting rls keywords depresin depression disability discapacidad esclerosis mltiple insomnia insomnio multiple sclerosis restless legs syndrome sndrome de piernas inquietas,0.0
effects flexible scheduling virtual visits burnout clinicians conclusions participants reported overall job satisfaction fs impact overall burnout fs likely indicate improvement control workload experienced reduced workrelated stress compared ss addition burnout likely 2039 year old age group suggesting special focus paid age group,0.0
frequent sign rare disease rare sign frequent disease read high interest study chen et al 2022 role optical coherence tomography oct first episode acute optic neuritis comparing 64 myelin oligodendrocyte glycoprotein antibodyassociated disease mogad patients 50 multiple sclerosis ms patients oct measurements within two weeks symptoms onset found mogad associated larger increase peripapillary retinal nerve fibers layer prnfl thickness ms moreover optimal prnfl cutoff 118 m determined youdens index provided sensitivity 74 specificity 82 discriminating mogad ms concluded oct helpful distinguishing acute mogad ms time presentation oct may provide guidance treatment acute results antibody testing return fully agree important finding however like stress conclusion mitigated taking account prevalence disease want oct provide guidance need know probability test will give correct diagnosis sensitivity specificity give information instead must estimate positive negative predictive values contrary sensitivity specificity directly depend prevalence disease altman bland 1994 using bayes theorem easy calculate positive negative predictive values corresponding published sensitivity specificity prevalence reflect clinical practice indeed ratio mogad vs ms current study reflect respective disease frequency routine practice prevalence ms mogad patients first episode acute precisely known tertiary referral centers can estimate ratio approximatively one mogad 7 ms patients deschamps et al 2017 exclude others aetiologies article chen et al 2022 notably high estimation mogad frequency since lower ratio described population studies around 1 10 hassan et al 2020 soelberg et al 2017 anyhow considering consecutives patients can estimate 125 mogad 875 ms taking account 74 sensitivity 82 specificity positive predictive value ie probability patient prnfl 118 m mogad among patients prnfl 118 m 37 less probability ms 63 importantly negative predictive value condition ie proportion patients prnfl 118 m mogad 96 others words absence prnfl thickening 118 m patients first episode acute makes diagnosis mogad unlikely,1.0
association cognition motor performance beyond structural damage relapsingremitting multiple sclerosis background previous studies demonstrated association motor cognitive performance multiple sclerosis ms however diseaserelated brain damage might represent common substrate phenomena considered objective aim study investigate whether association cognition motor function beyond structural damage patients ms methods eightyone healthy controls 106 relapsingremitting rr ms patients underwent 30 t mri quantification t2lesion volumes t1lesion volumes normalized brain volumes functional examination ninehole peg test 9hpt timed 25foot walk test t25fw expanded disability status scale neuropsychological evaluation brief repeatable battery neuropsychological tests also administered association demographic clinical cognitive mri functional measures analysed univariate analyses hierarchical linear regression results rrms patients spatial recall test symbol digit modalities test positively correlated 9hpt p 0001 t25fw p 0035 paced auditory serial addition test pasat correlated 9hpt p 0009 9hpt t25fw significantly associated normalized brain volumes p 0016 t2 t1lesion volumes p 0009 hierarchical regression models selected age normalized deep gray matter volume predictors t25fw adjustedr2 0109 younger age female sex higher normalized gray matter volume higher pasat 2 scores predicted higher 9hpt scores adjustedr2 0337 conclusions rrms patients deficit information processing speed executive function may contribute hand motor dysfunction beyond effect structural diseaserelated burden supporting integration motor cognitive assessment clinical settings keywords cognition executive function magnetic resonance imaging movement multiple sclerosis walking speed,0.0
beneficial effects spirulina consumption brain health spirulina microscopic filamentous cyanobacterium grows alkaline water bodies extensively utilized nutraceutical food supplement world due high levels functional compounds phycocyanins phenols polysaccharides antiinflammatory antioxidant immunomodulating properties vivo vitro several scientific publications suggested positive effects various pathologies cardiovascular diseases,0.0
chlorzoxazone alleviates experimental autoimmune encephalomyelitis via inhibiting il6 secretion dendritic cells multiple sclerosis ms chronic inflammatory demyelinating autoimmune disease chronic inflammatory demyelination cns experimental autoimmune encephalomyelitis eae important animal model study ms many pathological phenomena similar ms th17 cells important regulators eae ms pathogenesis cytokines needed th cell development secreted apcs dendritic cells dcs consequently ms improved inhibiting cytokine,1.0
oligoclonal bands clinical utility interpretation cues oligoclonal immunoglobulin g igg bands ocbs useful diagnostic tool detect central humoral response particular cerebrospinal fluid csf restricted ocbs represent hallmark multiple sclerosis ms can detected 90 cases support diagnosis although specific causative agent inducing b cell activation yet identified determination intrathecal igm including igm lipidspecific igm ocbs hand seems,0.0
strong tuberculin response bcg vaccination associated low multiple sclerosis risk populationbased cohort study background multiple sclerosis ms characterized inflammatory lesions central nervous system involving proinflammatory tcells immune dysregulation well described prevalent disease known whether precedes disease development bacillus calmettegurin bcg vaccination ameliorates mslike disease mice people vaccinated bcg tuberculin skin test tst offers standardized measure tcellmediated immune response therefore hypothesized strength tst response bcg vaccination associated subsequent ms risk methods using data norwegian tuberculosis screening programme 19631975 designed populationbased cohort study related size tst reactions individuals previously vaccinated bcg later ms disease identified norwegian ms registry fitted cox proportional hazard models flexible parametric survival models investigate association tst reactivity ms risk temporal relationship results among 279 891 participants 52 females 679 69 females later developed ms larger tst reactivity associated decreased ms risk hazard ratio ms per every 4mm increase skin induration size 086 95 confidence interval 076096 similar sexes strength association persisted 30 years tst conclusion strong vivo vaccine response bcg associated reduced ms risk 30 years later immunological mechanisms determining tst reactivity suggest skewed tcellmediated immunity precedes ms onset many decades keywords bacillus calmettegurin neurology cohort study immune responses multiple sclerosis neuroepidemiology neuroinflammation,0.0
association slowly expanding lesions mri disability people secondary progressive multiple sclerosis objectives explore relationship slowly expanding lesions sels mri disability secondary progressive multiple sclerosis spms methods retrospectively studied 345 patients spms enrolled mssmart trial nct01910259 underwent brain mri baseline 24 96 weeks definite sels defined concentrically expanding t2 lesions assessed nonlinear deformation volumetric t1weighted images associations sel volumes mri metrics disability assessed pearson correlations regression analysesresults averaged across patients 29 t2 lesions classified definite sels greater volume definite sels correlated higher total baseline t2 lesion volume r055 p0001 percentage brain volume reduction r026 p0001 higher number new persisting t1 black holes r019 p0001 subset 106 patients greater reduction magnetization transfer ratio adjusted difference052 p0001 regression analyses higher definite sel volume associated increasing disability assessed expanded disability status scale beta023 p0020 zscores multiple sclerosis functional composite beta 047 p0048 timed 25 foot walk test beta 210 p0001 paced auditory serial addition task beta 027 p0006 increased risk disability progression odds ratio192 p0025 conclusions definite sels represent almost one third t2 lesions spms associated neurodegenerative mri markers related clinical worsening suggesting may contribute disease progression new target therapeutic interventions,0.0
high prevalence intrathecal iga synthesis multiple sclerosis patients detection intrathecal iga synthesis ias multiple sclerosis ms underestimated assess develop highly sensitive assay based isoelectric focusing ief 151 ms patients 53 controls different neurological diseases recruited iga concentration analyzed using newly developed house elisa iga oligoclonal bands detect ias determined ief individuals showed iga concentration within normal range serum samples 9069,0.0
slowly expanding lesions new target progressive multiple sclerosis trials abstract,0.0
interaction nanoparticles immune system application treatment inflammatory diseases abstractnanoparticle np emerging tool applied biomedical field combination different materials adjustment physical chemical properties nanoparticles can diverse effects organism may change treating paradigm multiple diseases future results show nanoparticles can function immunomodulators formulas approved treatment inflammationrelated diseases however current understanding mechanisms nanoparticles can influence immune responses still limited systemic clinical trials necessary evaluation security longterm effects review provides overview recent advances nanoparticles can interact different cellular molecular components immune system application management inflammatory diseases caused abnormal immune reactions article focuses mechanisms interaction nanoparticles immune system tries provide reference future design nanotechnology treatment inflammatory diseasesgraphical abstract,0.0
engineering microbial consortia elizabethkingia meningoseptica escherichia coli strains biosynthesis vitamin k2 background study application microbial consortia topics interest fields metabolic engineering synthetic biology study report design optimisation elizabethkingia meningoseptica escherichia coli coculture bypass certain limitations found molecular modification e meningoseptica resistance many antibiotics fewer available molecular toolsresultsthe octaprenyl pyrophosphate synthase e meningoseptica sp f2 emopps expressed purified identified present study owing low vitamin k2 production e coli e meningoseptica sp f2 monoculture introduced e meningoseptica e coli coculture strategy improve vitamin k2 biosynthesis achieved production titres 32 mg l introducing vitamin k2 synthesisrelated genes e meningoseptica sp f2 e coli approximately threefold titre achieved e meningoseptica sp f2 monoculture study establishes foundation engineering mkn n 4 5 6 7 8 cocultivation system e meningoseptica e coli finally analysed surface morphology esterase activity membrane permeability microbial consortia using scanning electron microscopy confocal laser scanning microscopy flow cytometry respectively results showed cocultured bacteria closely linked lipase activity membrane permeability improved may conducive exchange substances bacteriaconclusionsour results demonstrated coculture engineering can useful method broad field metabolic engineering strains restricted molecular modifications,0.0
differentiating nonradiographic axial spondyloarthritis mimics narrative review background optimal treatment nonradiographic axial spondyloarthritis depends accurate timely diagnosis underlying disease however patients present common symptoms absence radiographic changes may confound diagnosismethods findingsin narrative review pubmed literature search conducted january 2021 date limits identify englishlanguage publications discussing classification nonradiographic axial spondyloarthritis emphasis clinical features presentation differential diagnoses mimics disease review describes epidemiology clinical features burden disease nonradiographic axial spondyloarthritis relates overall axial spondyloarthritis spectrum discusses mimics differential diagnoses nonradiographic axial spondyloarthritis considered evaluating patients suspected nonradiographic axial spondyloarthritis clinical practiceconclusionsrecognition clinical features nonradiographic axial spondyloarthritis along understanding comorbid conditions fibromyalgia allows differentiation mimics appropriate diagnosis nonradiographic axial spondyloarthritis important aggressive management disease reduce pain avoid loss function improve quality life,0.0
covid19 vaccine associated demyelination association mog antibody background chadox1s covishield vaxzervria astrazeneca bbv152 covaxin sarscov2 vaccines proven safe effective rare complications reportedobjective describe reports central nervous system cns demyelination following chadox1s bbv152 vaccinationsmethods results report 29 17 female mean 38 years cases cns demyelination twentyseven occurred temporal association chadox1s vaccine two association bbv152 vaccine eleven patients presentation myelitis six patients developed optic neuritis five acute demyelinating encephalomyelitis three presented brainstem demyelination four multiaxial involvement myelin oligodendrocyte glycoprotein mog antibodies positive ten patients one patient adem tumefactive demyelinating lesions died prolonged intensive care unit stay superimposed infection compared control group 87 postvaccinial cases found significantly higher mean age presence encephalopathy p value00007 csf pleocytosis p value 00094 raised csf protein p value 00062 conclusions difficult establish causal relationship vaccination neurological adverse events demyelination temporal association vaccination presence mog antibodies raises possibility immunogenic process triggered vaccine susceptible individuals,1.0
cinemeducation medicine mixed methods study students motivations benefits background cinemeducation courses used supplement standard teaching formats medical schools tend emphasise biopsychosocial aspects health purpose paper explore medical students attend cinemeducation course m23 cinema m23c lmu munich whether film screening subsequent expert peer discussion benefits studies future careers medical doctorsmethodsan exploratory sequential mixed methods study design used qualitative research ie three focus groups four expert interviews one group interview one narrative interview conducted inform subsequent quantitative survey qualitative data analysed using qualitative content analysis quantitative data analysed descriptively findings integrated using following thread protocolresultsin total 28 people interviewed 503 participants responded survey distributed seven m23c screenings participants perceive m23c informal teaching learn perspectives certain health topics combination film discussion spending time peers reasons reported benefits participation varied educational background participation frequency gender average participants gave 57 reasons attending m23c main reasons participating film topic ability discuss afterwards well spend evening peers attending m23c reported support students memory regards certain topics addressed m23c issues resurface later stage university courses hospital private lifeconclusionsthe m23c characterised unique combination film discussion encourages participants reflect upon opinions perspectives experiences participating m23c amplified understanding biopsychosocial aspects health illness students thus cinemeducative approaches m23c may contribute enabling health professionals develop apply humane empathetic relational skills,0.0
associations among quality life activities participation elderly residents joint contractures longterm care facilities crosssectional study background joint contractures degenerative osteoarthritis common joint diseases elderly population can lead limited mobility elderly individuals can exacerbate symptoms pain stiffness disability can interfere social participation quality life thus affecting mental health however relevant studies topic limited study describes associations joint contracture categories sites elderly residents longterm care facilities quality life activities participationmethodselderly individuals joint contractures residents longterm care facilities recruited world health organization quality life disability assessment schedule 20 used survey participants correlations multiple linear regressions multiple analyses variance joint contractures response variable used statistical analysisresultsthe final statistical analysis included 232 participants explanatory power contracture sites activities participation moderate strength association 2 113 compared elderly residents joint contractures osteoarthritis isolated upper limbs joint contractures osteoarthritis upper lower limbs significantly worse activity participation limitations significant differences activity participation found elderly residents joint contractures affecting upper limbs joint contractures affecting lower limbs f1 226 2604 f1 226 0674 nonsignificant osteoarthritis greatest impact activity limitations participation restrictions among elderly residents joint contractures affecting upper lower limbs f1 226 6251 p 014 conclusionselderly residents longterm care facilities belonging minority groups history stroke osteoarthritis high risk developing activity limitations participation restrictions moreover compared contraction sites regardless osteoarthritis joint contractures affecting upper lower limbs associated greatest activity limitations participation restrictionstrial registrationthis study registered chinese clinical trial registry registration number datechictr2000039889 13 11 2020,0.0
deep phenotyping reveals movement phenotypes mouse neurodevelopmental models background repetitive action resistance environmental change fine motor disruptions hallmarks autism spectrum disorder asd neurodevelopmental disorders vary considerably individual individual animal models conventional behavioral phenotyping captures finescale variations incompletely observed male female c57bl 6j mice methodically catalog adaptive movement multiple days examined two rodent models developmental disorders dynamic baseline investigated behavioral consequences cerebellumspecific deletion tsc1 protein wholebrain knockout cntnap2 protein mice mutations found clinical conditions associated asdmethodswe used advances computer vision deep learning namely generalized form highdimensional statistical analysis develop framework characterizing mouse movement multiple timescales using single popular behavioral assay openfield test pipeline takes virtual markers pose estimation find behavior clusters generate wavelet signatures behavior classes measured spatial temporal habituation new environment across minutes days different types selfgrooming locomotion gaitresultsboth cntnap2 knockouts l7tsc1 mutants showed forelimb lag gait l7tsc1 mutants cntnap2 knockouts showed complex defects multiday adaptation lacking tendency wildtype mice spend progressively time corners arena l7tsc1 mutant mice failure adapt took form maintained ambling turning locomotion overall decrease grooming however adaptation traits similar wildtype mice cntnap2 knockouts l7tsc1 mutant cntnap2 knockout mouse models showed different patterns behavioral state occupancylimitationsgenetic risk factors autism numerous tested two pipeline done conditions free behavior testing task social conditions reveal information behavioral dynamics variabilityconclusionsour automated pipeline deep phenotyping successfully captures modelspecific deviations adaptation movement well differences detailed structure behavioral dynamics reported deficits indicate deep phenotyping constitutes robust set asd symptoms may considered implementation clinical settings quantitative diagnosis criteria,0.0
interjoint coordination gait people multiple sclerosis focus effect disability backgroundwalking difficulties widespread among people ms pwms represent one major factors contributing physical disability may greatly affect individuals independence quality life context study lower limb kinematics may provide important contribution unveiling underlying mechanisms walking dysfunctions ms however limited information interjoint coordination gaitthe functional relationship joint pairs whole gait cycleis availablemethodswe retrospectively analyzed gait patterns 104 pwms 56 women 48 men mean age 463 average expanded disability status scale score 35 84 unaffected individuals ageandsexmatched underwent 3d computerized gait analysis carried using optical motion capture system pwms also stratified two groups according level disability edss 35 n 62 formed lowmild disability group edss 35 n 42 assigned moderatesevere disability group raw data processed calculate main spatiotemporal parameters kinematics sagittal plane hip knee ankle joints point gait cycle angular values employed build angleangle diagrams cyclograms hipknee kneeankle joint couples interjoint coordination quantified using geometric features cyclograms ie area perimeter dimensionless ratio compared groups pwms also explored possible relationships cyclograms parameters disability level spatiotemporal parameters gaitresultspwms exhibit wellknown gait pattern characterized reduced speed stride length increased step width double support phase duration interjoint coordination found altered hipknee kneeankle joint couples indicated significantly reduced cyclogram area perimeter respect unaffected individuals however detailed analysis angleangle diagram trajectories showed differences associated level disability particular pwms mildlow disability exhibit cyclograms partly superposed unaffected individuals first half stance phase hipknee couple second half swing phase kneeankle couple moderatesevere disability differences substantially extended whole gait cycle significant moderate large correlations also observed cyclogram area perimeter edss score spatiotemporal parameters gaitconclusionthe study interjoint coordination gait pwms represents useful source information way lower limb joints interact thus potentially expanding knowledge mechanisms underlying walking dysfunctions associated disease clinical perspective availability reference data covariation hipknee kneeankle joint angles gait can effectively support characterization progression disease assessment effectiveness rehabilitative treatments,0.0
lymphopenia multiple sclerosis patients treated ocrelizumab associated effect cd8 t cells backgroundin phase iii opera opera ii clinical trial lymphopenia reported 207 relapsingremitting multiple sclerosis rrms patients taking ocrelizumab ocr objectivethe objective study investigate effect ocr lymphocyte subtypes ms patients without lymphopeniamethodsretrospective study comparing lymphocyte subtypes ocrtreated ms patients low g1 normal g2 absolute lymphocyte count alc sixmonth followup cutoff 1000 106 l mann whitney u test used compare alc cd19 cd4 t cd8 t nk cell counts baseline sixmonth follow two groups linear mixed model applied compare changes alc subset counts proportions patients without lymphopenia performed analyses subpopulation nave treatment patients exclude possible influence previous disease modifying therapy dmt different kinetics observed two groupsresults one hundred sixtyseven patients included g1 n 34 g2 n 133 sixmonth followup compared baseline whole population observed significant reduction alc p00001 cd19 p00001 cd8 t p00288 lymphocytes also found increase cd4 cd8 ratio six months treatment p 00098 g1 showed lower alc g2 baseline six months mean alc 89641 15625 106 l g1 19099 62907 106 l g2 cd4 cd8 t cell mean counts lower p 00001 g1 g2 linear mixed model analysis found pronounced increase cd8 t percentage g2 g1 p 0008 nave treatment group fifty patients included cd4 cd8 t cell mean counts six months lower p 00074 p 00032 respectively g1 g2 linear mixed model analysis found pronounced decrease cd8 t cell count g1 g2 p 00103 furthermore found increase cd8 t percentage g2 whereas profound decrease cd8 t percentage observed g1 p 00052 adjusting confounders significantly positive correlations noted alc cd4 cd8 t cell counts negative correlation observed alc cd4 cd8 ratio driven low cd8 t cell countsconclusionocr decreases alc among t cells treatment predominantly impacts cd8 cells however cd8 t cell decrease pronounced patients lymphopenia studies needed establish relationship effect ocr alc cd8 t cells potential implication early clinical response risk viral infections,0.0
using causal methods map symptoms brain circuits neurodevelopment disorders moving identifying correlates developing treatments abstracta wide variety model systems experimental techniques can provide insight structure function human brain typical development neurodevelopmental disorders unfortunately work whether based manipulation animal models observational correlational methods humans high attrition rate translating scientific discovery practicable treatments therapies neurodevelopmental disorderswith new computational neuromodulatory approaches interrogating brain networks opportunities exist bedsideto bedsidetranslation potentially shorter path therapeutic options specifically methods like lesion network mapping can identify brain networks involved generation complex symptomatology acute onset lesionrelated symptoms focal developmental anomalies traditional neuroimaging can examine generalizability findings idiopathic populations noninvasive neuromodulation techniques transcranial magnetic stimulation provide ability targeted activation inhibition specific brain regions networks parallel realtime functional mri neurofeedback also allow endogenous neuromodulation specific targets may reach transcranial exogenous methodsdiscovery novel neuroanatomical circuits transdiagnostic symptoms neuroimagingbased endophenotypes may now feasible neurodevelopmental disorders using data cohorts focal brain anomalies novel circuits validation largescale highly characterized research cohorts tested prospectively using noninvasive neuromodulation neurofeedback techniques may represent new pathway symptombased targeted therapy,0.0
timed go tug cognitive manual tasks multiple sclerosis timed go tug cognitive manual tasks multiple sclerosis,0.0
impact covid19 pandemic prescription diseasemodifying therapy multiple sclerosis england nationwide study abstract available keywords covid19 multiple sclerosis,0.0
deep learningbased classification cancer cell leptomeningeal metastasis cytomorphologic features cerebrospinal fluid conclusion deep learning method developed assist lm diagnosis high accuracy low time consumption effectively thanks labeled data stepbystep training proposed method can successfully classify cancer cells csf assist lm diagnosis early addition unique research can predict cancers primary source lm relies cytomorphologic features without immunohistochemistry results show deep learning can widely used,0.0
evolution first clinical demyelinating even multiple sclerosis reflex trial regional susceptibility conversion multiple sclerosis disease onset amenability subcutaneous interferon beta1a abstract background purpose reflex trial clinicaltrialsgov identifier nct00404352 patients first clinical demyelinating event fcde displayed significantly delayed onset multiple sclerosis ms mcdonald criteria treated subcutaneous interferon 1a scifn1a versus placebo post hoc analysis evaluated effect scifn1a spatiotemporal evolution disease activity assessed changes t2 lesion distribution specific brain regions patients relationship conversion ms methods post hoc analysis baseline 24month mri data fcde patients received scifn1a 44 g three times weekly placebo reflex trial patients grouped according mcdonald ms status converter nonconverter treatment scifn1a placebo patient group baseline lesion probability map lpm longitudinal new enlarging shrinking disappearing lpms created lesion location frequency lesion occurrence assessed white matter wm results month 24 lesion frequency significantly higher anterior thalamic radiation atr corticospinal tract cst converters versus nonconverters p005 additionally overall distribution new enlarging lesions across brain month 24 similar placebo scifn1atreated patients ratio 095 patients treated scifn1a versus placebo showed significantly lower new lesion frequency specific brain regions cluster corrected atr p0025 superior longitudinal fasciculus p0042 cst p0048 inferior longitudinal fasciculus p0048 conclusions t2 lesion distribution specific brain locations predict conversion mcdonald ms show significantly reduced new lesion occurrence treatment scifn1a fcde population keywords first clinical demyelinating event interferonbeta lesions white matter tracts,1.0
immunological subsets characterization newly diagnosed relapsingremitting multiple sclerosis abstractobjectives using flow cytometry characterized myeloid b t cells patients recently diagnosed relapsingremitting multiple sclerosis rrms naive diseasemodifying therapies dmts methods prospective casecontrol study conducted tertiary ms center catania italy demographic clinical data peripheral bloods collected 52 naive patients recently diagnosed rrms sex agematched healthy controls hcs 21 ratio performed flow cytometry isolated peripheral blood mononuclear cells assess immune cell subsets differences rmms patients hcs explored biomarker potential cell subsets using receiver operating characteristic roc curves relative area curve auc analysesresults monocytic myeloidderived suppressor cells momdscs cd14+ hladr low inflammatory monocytes cd14+cd16+ displayed higher frequencies rrms patients compared hcs p 05 lower percentage bunswitched memory cells observed rrms patients compared hcs p 026 t cells higher frequency thelper cd4+ cells subset cd4+cd161+ rrms patients compared hcs p 001 roc analyses revealed auc 70 momdscs cd14+ hladr low inflammatory cd14+cd16+ thelper cd3+cd4+ thelper cd4+cd161+conclusions patients recent rrms diagnosis naive dmts showed peculiar myeloid b tcell immunophenotypeskeywords b cells t cells immunophenotype multiple sclerosis myeloid cells,0.0
perspectives experiences covid19 vaccines people ms background people ms may unique perspectives covid19 vaccines due condition medications objective assess perspectives experiences covid19 vaccination quantify variables impacting covid19 vaccine willingness people ms methods survey captured demographics ms characteristics covid19 infection exposures data opinions covid19 vaccine safety side effects efficacy experiences following vaccination chisquare tests logistic regression model used denote betweengroup differences variables predicting vaccine willingness respectively results 878 237 participants willing receive vaccine fifteen percent held delayed dmt dose vaccination ms symptoms worsened minority 76 first dose 147 second dose side effects mild 800 553 planning receive vaccine primarily concerned longterm safety 704 medical comorbidities adjusted odds ratio aor 5222 p004 following infection prevention precautions aor6330 p0008 associated vaccine willingness conclusion individuals ms surveyed plan receive covid19 vaccine people ms experience similar side effects general population experience transient ms symptom worsening results can inform conversations vaccination providers people ms keywords covid19 multiple sclerosis vaccine,0.0
prevention ms requires intervention causes disease reconciling genes epigenetics epstein barr virus prevention multiple sclerosis requires intervention modifiable causes condition making necessary establish causes ms often stated polygenic disease causal contributions environmental factors geneenvironment interactions implying additive independent relationship factors mechanistically independent contributions genes environmental factors traits model unrealistic still useful,0.0
causal biological network models reactive astrogliosis systems approach neuroinflammation astrocytes play central role neuroimmune response responding cns pathologies diverse molecular morphological changes process reactive astrogliosis used computational biological network model mathematical algorithms allow interpretation highthroughput transcriptomic datasets context known biology study reactive astrogliosis gathered available mechanistic information literature comprehensive causal,0.0
immune system enter brain multiple sclerosis ms considered frequent inflammatory demyelinating disease central nervous system cns occurs variable prevalence across world rich armamentarium disease modifying therapies selectively targeting specific actions immune system available treatment ms understanding immune cells primed access cns ms immunomodulatory treatments affect neuroinflammation requires proper,1.0
integrated analysis differentially expressed genes cerna network identify hub lncrnas potential drugs multiple sclerosis abstractobjective multiple sclerosis ms autoimmune neuroinflammatory disease nervous system however precise molecular mechanisms underlying ms yet fully elucidated study aim provide novel insight pathogenesis ms provide resource identifying new biomarkers therapeutics msmethods study analyzed gene expression profiles gse21942 mirna expression profiles gse61741 ms patient samples downloaded geo database identified differentially expressed mrnas mirnas demrnas demirnas next constructed proteinprotein interaction ppi network msspecific cerna network mcen integrating expression profiles interaction pairs mrnamirnas lncrnamirnas according modular structure ppi network identified hub demrnas generated cerna subnetwork analyze key lncrnas associated msresults first identified 4 modules constructing ppi network using demrnas functional enrichment analysis showed modules enriched immunerelated pathways constructed mcen hub geneassociated cerna subnetwork using comprehensive computational approach identified three key lncrnas linc00649 tp73as1 malat1 identified key lncrnamediated cernas within subnetwork finally analyzing linc00649mir1275cd20 identified 6 drugs may represent novel drugs msconclusion collectively results provide novel insight discovery biomarkers therapeutics ms provide suitable foundation design future investigations pathogenic mechanisms associated mskeywords multiple sclerosis biomarker cerna cerna network lncrna,0.0
magnetic resonance imaging criteria onset differentiate pediatric multiple sclerosis acute disseminated encephalomyelitis nationwide cohort study backgroundbrain mri critical distinguishing pediatric ms acute disseminated encephalomyelitis adem aim propose mri criteria distinguish ms monophasic adem based first brain mri validate previously proposed mri criteriamethodsa neuroradiologist undertook retrospective evaluation mri first demyelinating event children 18 years medical recordvalidated ms adem denmark 200815 used forward stepwise logistic regression identify mri categories differed significantly ms adem estimated accuracy statistics mri criteria distinguish ms ademresultsthe monophasic adem cohort n46 nationwide populationbased 200815 median age onset 53 years range 08172 children least five years followup ensure monophasic disease course children ms n67 median age onset 163 years range 33179 least two categories best distinguished ms monophasic adem area curve 83 89 corpus callosum long axis perpendicular lesion b welldefined lesions c absence basal ganglia thalamus lesion corpus callosum long axis perpendicular lesion b welldefined lesions c absence diffuse large lesions d black holes callen kidmus ipmssg criteria performed well mcdonald 2017 barkhof magnims verhey criteria poorer performanceconclusionthis study provides class ii evidence brain mri good performance differentiating ms monophasic adem onset,1.0
association socioeconomic disadvantage neighborhood disparities clinical outcomes multiple sclerosis patients background socioeconomic disadvantage may important contributor clinical outcomes ms well understood objective examine associations area deprivation index adi validated measure neighborhoodlevel disadvantage clinical outcomesmethods assessed longitudinal association ms performance test mspt quality life neurological disorders neuroqol measures adi quartiles q1 lowest deprivation q4 highest deprivation relapsing remitting ms rrms progressive ms cohortsresults study included 2 921 patients 658 rrms 341 progressive ms 13 715 visits patients living disadvantaged areas almost universal worsening baseline mspt neuroqol scores p 005 compared patients living areas lowest deprivation manual dexterity test mdt illustrated particular disparity rrms patients living greatest area deprivation mdt score averaged 29 seconds longer someone living areas least deprivation longitudinal analysis illustrated less favorable mspt neuroqol outcomes across visits q1 versus q4 adi quartiles within rrms cohort within progressive ms cohort adjustment linearly increasing area deprivation scores reflected less favorable processing speed test pst six neuroqol outcomes among rrms cohort within progressive cohort higher deprivation associated less favorable mdt pst 11 12 neuroqol outcome measuresconclusions study provides evidence socioeconomic disadvantage risk factor disability accrual ms may targeted improve care informing resource allocation,0.0
risk covid19 infection severe disease ms patients different diseasemodifying therapies background risk sarscov2 infection severity disease modifying therapies dmts multiple sclerosis ms remains unclear studies demonstrating increased risks infection bcelldepleting anticd20 therapies severity others fail observe association existing studies limited reliance numerator data ie covid19 cases onlyobjective assess risks covid19 dmt study aimed assess numerator patients sarscov2 infection denominator data patients treated dmts interest determine dmts impart increased risk sarscov2 infection disease severitymethods systematically reviewed charts queried patients clinic encounters nyu ms comprehensive care center msccc evidence covid19 patients commonly used dmts clinic sphingosine1phosphate receptor s1p modulators fingolimod siponimod rituximab ocrelizumab fumarates dimethyl fumarate diroximel fumarate natalizumab covid19 status determined clinical symptoms cdc case definition laboratory testing available sarscov2 pcr sarscov2 igg multivariable analyses conducted determine predictors infection severe disease hospitalization death using sarscov2 infected individuals per dmt group individuals given dmt denominatorresults identified 1 439 ms patients dmts interest 230 labconfirmed n173 752 suspected n57 248 covid19 infection frequent rituximab 35 138 254 followed fumarates 39 217 180 s1p modulators 43 250 172 natalizumab 36 245 147 ocrelizumab 77 589 131 14 hospitalizations 2 deaths dmt found significantly associated increased risk sarscov2 infection rituximab predictor severe sarscov2 infection among patients sarscov2 infection 67 95 ci 11417 reach statistical significance entire patient population dmt used 28 95 ci 06122 dmt associated increased risk severe covid19conclusions analysis covid19 risk among patients commonly used dmts demonstrate increased risk infection dmt rituximab associated increased risk severe disease,0.0
computational pathology musculoskeletal conditions using machine learning advances trends challenges abstracthistopathology widely used analyze clinical biopsy specimens tissues preclinical models variety musculoskeletal conditions histological assessment relies scoring systems require expertise time resources can lead analysis bottleneck recent advancements digital imaging image processing provide opportunity automate histological analyses implementing advanced statistical models machine learning deep learning greatly benefit musculoskeletal field review provides highlevel overview machine learning applications general pipeline tissue collection model selection highlights development image analysis methods including machine learning applications solve musculoskeletal problems discuss optimization steps tissue processing sectioning staining imaging critical successful generalizability automated image analysis model also commenting considerations taken account model selection considerable advances field computer vision outside histopathology can leveraged image analysis finally provide historic perspective previously used histopathological image analysis applications musculoskeletal diseases contrast advantages implementing stateoftheart computational pathology approaches deep learning approaches used significant opportunity expand use approaches solve musculoskeletal problems,0.0
microbiota restrains neurodegenerative microglia model amyotrophic lateral sclerosis background gut microbiota can affect neurologic disease shaping microglia primary immune cell central nervous system cns antibiotics improve models alzheimers disease parkinsons disease multiple sclerosis c9orf72 model amyotrophic lateral sclerosis als antibiotics worsen disease progression sod1g93a model als als microglia transition homeostatic neurodegenerative mgnd phenotype contribute disease pathogenesis whether switch can affected microbiota investigatedresultsin short report found lowdose antibiotic treatment worsened motor function decreased survival sod1 mice consistent studies using highdose antibiotics also found cohousing sod1 mice wildtype mice effect disease progression investigated changes microbiome found antibiotics reduced akkermansia butyrateproducing bacteria may beneficial als cohousing little effect microbiome investigate changes cns resident immune cells sorted spinal cord microglia found antibiotics downregulated homeostatic genes increased neurodegenerative disease genes sod1 mice furthermore antibioticinduced changes microglia preceded changes motor function suggesting may contributing disease progressionconclusionsour findings suggest microbiota play protective role sod1 model als restraining mgnd microglia opposite neurologic disease models sheds new light importance diseasespecific interactions microbiota microglia video abstract,0.0
transcriptomic characterization tissues patients subsequent pathway analyses reveal biological pathways implicated spastic ataxia background spastic ataxias sas encompass group rare severe neurodegenerative diseases characterized overlap ataxia spastic paraplegia clinical features associated pathogenic variants number genes including gba2 gene codes nonlysososomal glucosylceramidase involved sphingolipid metabolism catalytic role degradation glucosylceramide however mechanism gba2 variants lead development sa still unclearmethodsin work perform nextgeneration rnasequencing rnaseq attempt discover differentially expressed genes degs lymphoblastoid fibroblast cell lines induced pluripotent stem cellderived neurons derived patients sa homozygous gba2 c1780g c missense variant exploit degs pathway analyses order elucidate candidate molecular mechanisms implicated development gba2 geneassociated saresultsour data reveal total 5217 genes significantly altered expression patient control tested tissues furthermore significant extracted pathways presented discussed possible role pathogenesis disease among oxidative stress neuroinflammation sphingolipid signaling metabolism pi3kakt mapk signaling pathwaysconclusionsoverall work examines first time transcriptome profiles gba2associated sa patients suggests pathways pathway synergies possibly role sa pathogenesis lastly provides list degs pathways validated towards discovery disease biomarkers,0.0
elevated serum extracellular vesicle arginase 1 type 2 diabetes mellitus crosssectional study middleaged elderly population background serum extracellular vesicle ev derived arginase 1 arg 1 plays critical role diabetesassociated endothelial dysfunction study performed determine levels serum evderived arg 1 t2dm nont2dm participants examine association serum evderived arg 1 t2dm incidencemethodswe performed crosssectional study 103 chinese including 73 t2dm patients 30 nont2dm serum evs prepared via ultracentrifugation serum evderived arg 1 levels measured enzymelinked immunosorbent assay correlations serum evderived arg 1 clinical variables analyzed association serum evderived arg 1 levels t2dm determined multivariate logistic regression analysis interaction subgroup analysis used evaluate interaction relevant baselines association serum evderived arg 1 levels t2dmresultsserum evderived arg 1 levels significantly higher t2dm patients compared nont2dm patients p 0001 correlation analysis revealed serum evderived arg 1 levels positively associated fasting plasma glucose fpg r 0316 p 0001 glycated hemoglobin hba1c r 0322 p 0001 serum evderived arg 1 levels significantly associated t2dm especially subgroup t2dm 10 years 1651 95 ci 10662557 p value 0025 adjusting confounding factorsconclusionselevated concentration serum evderived arg 1 closely associated t2dm,0.0
differential antibody response covid19 vaccines across immunomodulatory therapies multiple sclerosis background prior studies suggest reduced humoral response covid19 vaccination immunosuppressed populations disease modifying therapies dmts multiple sclerosis ms variable immunomodulatory effects limited data available dmts aimed determine impact dmts antibody response covid19 vaccination among ms patientsmethods patients documented covid19 vaccination dates antispike antibody results postvaccination identified marchaugust 2021 clinical data retrospectively abstracted chart review deidentified data analyzed evaluate antibody response multivariable logistic regression analyses used identify clinical demographic predictors antibody response data analysis completed sas studio v38results total 353 individuals documented covid19 vaccine antibody test dates 58 pfizer 38 moderna 4 johnson johnson 353 patients 72 developed antibodies mean antibody test interval 53 days median 46 post final vaccine dose 100 dmt n34 injectables n20 teriflunomide n10 natalizumab n71 978 fumarates n46 47 positive antibody result one patient cladribine n1 negative antibody result sphingosine1 phosphate s1p modulators 724 n21 29 positive antibody result anticd20 therapies 376 n53 141 positive antibody result multivariate modeling total cohort showed anticd20 therapy significantly associated lower odds positive antibody response or0024 95 ci 001 005 p00001 among s1p modulators increased duration therapy lymphopenia may associated lower odds positive antibody response multivariate modeling anticd20 therapies showed therapy duration 1 year 814 95 ci 2896 22898 p0001 prior covid19 infection or395 95 ci 1137 13726 p03 significantly associated higher odds positive antibody response patients recent bcell data mean bcell count higher antibodypositive individuals compared antibodynegative 329 vs 39 cells p0056 conclusion ms dmts variable impact antibody response mrna viral vector covid19 vaccines patients dmt interferons glatiramer acetate teriflunomide natalizumab nearly fumarates positive antibody responses postvaccine s1p modulators anticd20 therapies attenuated antibody response postvaccine patients anticd20 therapies shorter duration therapy prior covid19 infection predicted positive antibody response studies needed determine clinical significance antibody testing development cellular mediated immunity benefits booster vaccinations,0.0
disentangling selfreported fatigue depression cognitive impairment people multiple sclerosis backgroundfatigue common problem among people multiple sclerosis ms can negative effect mental physical social function selfreported measures ms fatigue often operationalized multidimensional symptom however questions remain best account multidimensional aspects selfreported fatigue whether aspects distinct entities thus purpose study explore overlap distinctions selfreported measures severity impact fatigue mental physical fatigue mental fatigue depressive symptoms cognitive impairmentmethodsan observational study conducted 289 participants ms completed questionnaires baseline questionnaires unidimensional fatigue impact scale ufis chalder fatigue scale cfs fatigue scale motor cognitive functions fsmc multiple sclerosis neuropsychological screening questionnaire msnsq quality life neurological disorders short form depression neuroqol spearmans correlation coefficient used examine bivariate correlations composite subscale scores exploratory structural equation modeling esem used determine factor structure prespecified number factors retain modeling multiple items across questionnaires examine model fit subsequently poor fitting models iterative procedure determine better fitting multidimensional model posited bifactor confirmatory factor analysis modelresultsthe bivariate correlation analysis revealed subscales questionnaire measuring different aspects fatigue highest correlations r061068 subscales different questionnaires measuring aspect fatigue next highest correlations r042060 subscales different questionnaires measuring different aspects fatigue lowest correlations r034040 bifactor models general fatigue factor subdomains pertaining impact severity mental physical fatigue relatively good model fits compared models omitting subdomains however esem model using subscales cfs fsmc fit poorly adequately identify separate factors mental physical fatigue esem model separate factors selfreported mental fatigue depressive symptoms cognitive impairment good fitconclusionsthe working study hypothesis fatigue constructs moderately correlated yet distinct entities generally supported results study however found hypothesized separation latent dimension existed items subscales came questionnaire case level specificity terms target action context time elements measuring fatigue consistent implications principle compatibility measuring selfreported ms fatigue discussed,0.0
chromatin accessibility transcriptome integrative analysis revealed ap1mediated genes potentially modulate histopathology features psoriasis background psoriasis chronic hyperproliferative skin disease featured hyperkeratosis parakeratosis munro microabscess elongation rete pegs granulosa thinning lymphocyte infiltration previously profiled gene expression chromatin accessibility psoriatic skins transcriptome sequencing atacseq however integrating datasets unravel gene expression regulation lacking integrated transcriptome atacseq psoriatic normal skin tissues trying leverage potential role chromatin accessibility function histopathology features resultsby inducing binding expression target analysis beta algorithms explored target prediction transcription factors binding 15 psoriatic 19 control skins beta identified 408 upregulated genes rank product 001 133 downregulated genes linked chromatin accessibility noticed cumulative fraction genes upregulation group statistically higher background genes downregulation group significant kegg pathway analysis showed upregulated 408 genes enriched tnf nod il17 signaling pathways addition motif module beta suggested 57 upregulated genes targeted transcription factor ap1 indicating increased chromatin accessibility facilitated binding ap1 target regions induced expression relevant genes among genes sqle strn eif4 myo1b expression increased patients hyperkeratosis parakeratosis acanthosis thickeningconclusionsin summary advantage beta identified series genes contribute disease pathogenesis especially modulating histopathology features providing us new clues treating psoriasis,0.0
autologous treatment als implication broad neuroprotection background amyotrophic lateral sclerosis als characterized progressive loss motor neurons mns leading paralysis respiratory failure death within 25 years diagnosis exact mechanisms sporadic als comprises 90 cases remain unknown familial als mutations superoxide dismutase sod1 cause 10 casesmethodsals patientderived humaninduced pluripotent stem cells als hipscs harboring sod1av4 mutation differentiated mns alsmns neuroprotective effects conditioned medium cm hescs h9 wt hipscs wtc11 als ipscs mn apoptosis viability formation maintenance neurites mitochondrial activity expression inflammatory genes examined vivo studies 200 l cm als ipscs cs07 cs053 injected subcutaneously als model mice transgenic human sod1g93a mutation animal agility strength muscle innervation mass neurological score onset paralysis lifespan als mice assayed observing significant diseasemodifying effects cm characterized biochemically fractionation comparative proteomics epigenetic screens dependence pluripotency cm fibroblasts differentiated wt hipscs lacked neuroprotective activity used negative control throughout studiesresultsthe secretome pscs including als patient ipscs neuroprotective h2o2 model model pathogenic sod1 mutation als ipsccm attenuated examined hallmarks als pathology rescued human alsmns denervation death restored mitochondrial health reduced expression inflammatory genes als ipsccm also improved neuromuscular health function delayed paralysis morbidity als mice compared side side cyclosporine csa mitochondrial membrane blocker prevents leakage mitochondrial dna failed avert death alsmns although csa als ipsccm equally stabilized mn mitochondria attenuated inflammatory genes biochemical characterization comparative proteomics epigenetic screen suggested interactome several key proteins different fractions psccm delivered multifaceted neuroprotectionconclusionsthis work introduces mechanistically characterizes new biologic treating als complex neurodegenerative diseases,1.0
visual analog scale fatigue vasf multiple sclerosis ms visual analog scale fatigue vasf multiple sclerosis ms,0.0
bdnf val66met polymorphism associated motor recovery rehabilitation progressive multiple sclerosis patients background rehabilitation fundamental progressive multiple sclerosis ms predictive biomarkers motor recovery lacking making patient selection difficult motor recovery depends synaptic plasticity brainderived neurotrophic factor bdnf key player binding neurotrophictyrosine kinase2 ntrk2 receptor therefore genetic polymorphisms bdnf pathway may impact motor recovery wellknown polymorphism bdnf gene rs6265 causes valine methionine substitution val66met influences memory motor learning healthy individuals neurodegenerative diseases date studies explored whether polymorphisms bdnf ntrk2 genes may impact motor recovery ms objectives assess whether genetic variants bdnf ntrk2 genes affect motor recovery rehabilitation progressive ms methods association motor recovery intensive neurorehabilitation polymorphisms bdnf rs6265 ntkr2 receptor rs2289656 rs1212171 assessed using sixminuteswalkingtest 6mwt 10metrestest 10mt nineholepegtest 9hpt 100 progressive ms patients results observed greater improvement 6mwt rehabilitation carriers bdnf val66met substitution compared bdnf val homozygotes p 0024 significant association found 10mt 9hpt ntrk2 polymorphisms affect results motor function tests conclusion bdnf val66met associated walking function improvement rehabilitation progressive ms patients result line previous evidence showing protective effect val66met substitution brain atrophy ms larger studies needed explore potential predictive biomarker rehabilitation outcome keywords bdnf biomarker motor recovery multiple sclerosis neurotrophin progressive rehabilitation,0.0
cerebrospinal fluid progressive multiple sclerosis patients reduces differentiation immune functions oligodendrocyte progenitor cells oligodendrocyte progenitor cells opcs responsible remyelination central nervous system cns health disease patients multiple sclerosis ms remyelination always successful mechanisms differentiating successful failed remyelination wellknown growing evidence suggests immune role opcs addition regenerative role however clear helps hinders regenerative process studied effect,1.0
molecular research multiple sclerosis special issue molecular research multiple sclerosis provides better comprehension disease establishes possible new biomarkers ensure better care ms patients future contains review contribution metabolomics ms 1 impact sarscov2 infection 2 review common micrornas mirnas ms major depression md 3 first case comorbid ms phelan mcdermid syndrome pmcd regressive symptoms young woman improved treatment methylprednisolone 4 review intrathecal inflammation progressive ms 5 molecular research includes finding biomarkers diagnosis prognosis therapy response monitoring ms comorbidities molecular changes highlighted articles special issue means providing better comprehension diseasethe first tool better comprehension ms metabolomics 1 review contribution metabolomics emphasizes patients different phenotypes different time points diagnosis higher scylloinositol glutamine reported ms higher acetate glutamate lactate lysine reported neuromyelitis optica considered form ms prognosis evidence molecular mechanisms involved ms shown oxidative nitrosative stress kynurenine pathway relapsingremitting ms rrms chronic progressive ms eight biochemical pathways differences csf rrsm secondary progressive ms spms additionally ms patients plasma glycerophospholipids found abundant high body mass index connected increase ceramides regarding treatment response metabolomics useful tool describing response different drugs interferon beta1a glatiramer acetate another interesting aspect review metaanalysis conducted evaluate individual group effects metabolites upregulated different fluids csf blood urine ms patients highlight pathways likely play role 1 data integration milestone omics approaches demonstrated rispoli et al 1 monaco et al 5 special issue integrating results metabolomics neuroimaging data rispoli et al showed significant reduction arginine plasma concentration rrms higher concentration indolepyruvate spms compared rrms also higher concentration myelin basic protein macrophagederived chemokine 56dihydroxyprostaglandin highlighted worse disease progression spms 1 similar approach monaco et als article focusing intrathecal inflammation pms neuropathology molecular mri methodologies integrated showing molecules connected higher meningeal inflammation grey matter demyelination namely ifn tnf il2 il22 cxcl13 cxcl10 lt il6 il10 5 another important point molecular research role intrathecal inflammation compartmentalized cns nonneural tissues pms 5 indeed intrathecal inflammation part clinical pathological progression ms need clarify compartmentalization cellular inflammation occurs review authors emphasize molecules connected subpial lesions csf meningeal choroid plexus inflammation recent findings composition csf cellular trafficking molecular exchange compartments authors hypothesize proinflammatory milieu can damage tissues bathed studies needed point mechanisms behind promotion maintenance intrathecal inflammation 5 context mention recent work showing skull vertebral bone marrow source immune cells accumulate dura without passing blood 6 also intrathecal inflammation thought affect csf flow rate pulses interestingly recently shown csf flow affected circadian cycle 7 disruption normal csf circulation thought connected neurodegenerative diseases 8 increased interest understanding mechanism disrupted csf flow rate pulses ongoing inflammation whether contributes clears brain inflammationtwo papers highlight fact comorbidities must considered disease management 3 4 two comorbidities discussed namely md 3 pmcd 4 first md present 50 ms patients shares abnormalities neuroinflammation peripheral inflammation gut dysbiosis chronic oxidative nitrosative stress neuroendocrine abnormalities mitochondrial dysfunction analysis mirna regulation two diseases helps understand pathologies connected helps develop treatments reduce depression ms patients therefore author published nonexhaustive table 67 mirnas discussed expression ms md example importance considering md morbidity ms management shown ifn treatment incidence rate depression greater 01 probably due interaction immune endocrine neuronal pathways 3 second first case comorbid ms pmcd regressive symptoms young woman improved treatment methylprednisolone discussed 4 goal paper evaluate incidence pmcd ms coincidental correlation pathophysiology involvement shank3 igf1 cases needed confirm hypotheses however first case shows importance additional diagnostics patients pmcd regressive symptoms 4 finally another significant contribution molecular research ms review impact sarscov2 infection understand neurodegeneration processes common molecular pathways vascular damage ms 2 paper highlights sarscov2 potentially induces demyelination humans fact spike s glycoprotein sarscov2 binds receptor ace2 highly expressed respiratory epithelial cells neurons glial cells ms models induced different viruses murine coronavirus already exist leading demyelination mice humans principal suspects cytokine storms activation immune cells detailed authors also review emphasizes opposed thought higher risk infection ms patients taking diseasemodifying therapies dmts immunosuppressive effects case reports describe enhanced risk hospitalization fatal outcome surprisingly dmts even protective effect cytokine storm observed covid19 finally authors point enhancement vascular damage ms patients sarscov2 infection three types vascular dysfunctions known ms namely cardiovascular incidents chronic cerebral hypoperfusion chronic cerebrospinal venous insufficiency vascular damage ms connected excessive blood platelets activity interacting leukocytes leading increase autoreactive t cell infiltration cns therefore increases number neuroinflammatory lesions strong expression ace2 cns found perivascular astrocytes largely eliminated ms predict low level ace2 therefore reducing chance virus entering ms patients decreasing neurological complications however possible predict using one factor eg decreased expression ace2 several others influence 2 conclusion date biomarkers sensitive specific enough used population screening also sources interindividual variability must considered ms complex heterogeneous disease integrates crosses pathologies generating unexpected effects case md pmcd infections covid19 therefore single molecular marker unlikely exist efforts molecular research multiple sclerosis made towards integrating analytic approaches including clinical characteristics mri variables proteins metabolite concentrations create signatures ms disease diagnosis prognosis treatment response,1.0
results patient interviews fatigue progressive multiple sclerosis evaluation fatigue patientreported outcome pro instruments abstract introduction fatigue one common debilitating symptoms multiple sclerosis ms challenging assess comprehensively characterized patients progressive ms study aimed 1 obtain qualitative evidence patients progressive ms characterize msrelated fatigue concepts impacts healthrelated quality life hrqol 2 evaluate conceptual frameworks existing msspecific fatigue patientreported outcome pro instruments using study data determine suitable pro instrument population methods qualitative interviews conducted 30 us participants confirmed progressive ms fatigue last 6 months assess msrelated fatigue data compared concepts existing pro instruments evaluate relevance progressive ms results physical mental concepts fatigue identified characterized distinctly patients progressive ms patients characterized fatigue occurring daily lasting several hours negative impacts hrqol concept mapping existing msspecific fatigue pro instruments supported fatigue severity impact questionnairerelapsing multiple sclerosis fsiqrms suitable existing option assessing fatigue patients progressive ms separates physical mental aspects fatigue includes every highly endorsed concept reported interviewed patients conclusions qualitative study identified meaningful physical mental fatigue concepts patients progressive ms preliminarily supports use fsiqrms population research needed fully validate instrument progressive ms keywords fatigue fatigue severity impact questionnairerelapsing multiple sclerosis fsiqrms patientreported outcome pro primary secondary progressive multiple sclerosis ppms spms progressive multiple sclerosis progressive ms qualitative patient interview study,0.0
astrocytic junctional adhesion moleculea regulates tcell entry past glia limitans promote central nervous system autoimmune attack contactmediated interactions astrocytic endfeet infiltrating immune cells within perivascular space underexplored yet represent potential regulatory checkpoints cns autoimmune disease disability reactive astrocytes upregulate junctional adhesion moleculea immunoglobulinlike cell surface receptor binds t cells via ligand integrin lymphocyte functionassociated antigen1 tested role astrocytic junctional adhesion,0.0
role astrocytes prionlike mechanisms neurodegeneration accumulating evidence suggests neurodegenerative diseases merely neuronal nature comprise multicellular involvement astrocytes emerging key players pathomechanisms several neurodegenerative diseases involve deposition misfolded protein aggregates neurons characteristic prionlike behaviours templatedirected seeding intercellular propagation distinct conformational strains proteinmediated toxicity role astrocytes,0.0
women female infertility seeking medically assisted reproduction increased risk developing multiple sclerosis abstract study question female infertility among women seeking medically assisted reproduction mar associated prevalent well incident multiple sclerosis ms summary answer women record female infertility increased risk developing ms compared apparent fertile women however prevalence ms slightly higher among women undergoing mar compared women child without mar related origin infertility ie male versus female factor infertility known already women ms fewer children compared women without ms persons ms often coexisting autoimmune disorders including hypothyroidism compared general population thyroid dysfunction associated ovarian cause infertility miscarriage ovarian failure conversely women endometriosis highly associated infertility also often coexisting autoimmune diseases including ms hypothyroidism compared general population however whether low fertility rate among women ms due genetically predisposition autoimmune endocrine disorders leads reduced fertility active choice woman diseaserelated pathology treatmentspecific effect endocrine ovarian function completely understood study design size duration registerbased cohort study total 310 357 women 1996 2018 crosssectional design used analysing prevalence ms whereas cohort design 24 years followup used analysing incidence ms participants materials setting methods three cohorts included study 55 404 women female infertility diagnosis registered danish ivf register ii 25 096 women male factor infertility recorded ivf register thus female infertility diagnosis iii 229 857 age calendarmatched women record first child birth danish medical birth register dmbr record ever ivf register prevalence incidence ms female infertility cohort compared two control cohorts apparent fertile women using logbinomial regression cox proportional hazard regression respectively main results role chance crude prevalence ms per 1000 persons 32 women undergone mar treatment regardless origin infertility ie male versus female factor infertility 23 fertile dmbr controls age calendar educational level adjusted prevalence ratio diagnosis ms first mar treatment 127 95 ci 107152 infertile women compared fertile dmbr controls 100 95 ci 077131 comparison women male partner infertility also undergone mar treatment found association incident ms female infertility compared either control groups fertile women limitations reason caution cohort infertile women highly selected basis choice fertility treatment thus include women unestablished infertility women reason chosen mar treatment additionally due nature observational study design exclude possibility unmeasured residual confounding wider implications findings results suggest women ms may undergo mar treatment often women without ms due awareness possibility mar treatments sexual dysfunction related ms disease also need timing pregnancy avoid unnecessary long time period without disease modifying therapyespecially high efficacyand hence wish conceive quickly findings important clinicians dealing women ms childbearing age study funding competing interest s authors received financial support study tik served scientific advisory board novartis received support congress participation biogen mm served scientific advisory boards biogen sanofi roche novartis merck abbvie alexion received honoraria lecturing biogen merck novartis sanofi genzyme received research support support congress participation biogen genzyme roche merck novartis remaining authors declare conflict interest trial registration number n keywords ivf cohort study female infertility medically assisted reproduction multiple sclerosis,0.0
serum expression level highmobility group box 1 hmgb1 multiple sclerosis patients relationship physical psychological status 12month followup study newly diagnosed ms patients background strong need identify simple costeffective biomarkers multiple sclerosis ms objectives evaluate serum levels receptor advanced glycation end products rage ligand highmobility group box hmgb 1 correlation changes physical psychological indicators ms patients methods 12month followup serum level hmgb1 expanded disability status scale edss score rate clinical relapse quality life psychological indicators assessed baseline 6 months 12 months compared 60 newly diagnosed ms patients 60 healthy controls hcs data analyzed using ttest mannwhitney u test twoway repeated measures analysis variance anova spearmans rank correlation coefficient results significant decrease observed edss score p 0001 significant increase serum level hmgb1 ms patients p 0009 serum level hmgb1 higher ms patients compared hcs baseline 658 p 0007 sixmonth followup 739 p 0004 12month followup 776 p 0021 significant positive correlations serum level hmgb1 scores ms impact scalepsychological subscale msisps r 059 p 0001 beck depression inventory bdi r 0491 p 0031 pittsburgh sleep quality index psqi r 0471 p 0035 conclusion serum level hmgb1 predict patients psychiatric status better physical status keywords advanced glycation hmgb1 multiple sclerosis psychiatric status,0.0
efficacy safety ofatumumab recently diagnosed treatmentnaive patients multiple sclerosis results asclepios ii background phase iii asclepios ii trials participants relapsing multiple sclerosis receiving ofatumumab significantly better clinical magnetic resonance imaging mri outcomes receiving teriflunomide objectives assess efficacy safety ofatumumab versus teriflunomide recently diagnosed treatmentnaive rdtn participants asclepios methods participants randomized receive ofatumumab 20 mg subcutaneously every 4 weeks teriflunomide 14 mg orally daily 30 months endpoints analysed post hoc protocoldefined rdtn population included annualized relapse rate arr confirmed disability worsening cdw progression independent relapse activity pira adverse events results data analysed 615 rdtn participants ofatumumab n 314 teriflunomide n 301 compared teriflunomide ofatumumab reduced arr 50 rate ratio 95 confidence interval ci 050 033 074 p 0001 delayed 6month cdw 46 hazard ratio hr 95 ci 054 030 098 p 0044 6month pira 56 hr 044 020 100 p 0049 safety findings manageable consistent overall asclepios population conclusion favourable benefitrisk profile ofatumumab versus teriflunomide supports consideration firstline therapy rdtn patientsasclepios ii registered clinicaltrialsgov nct02792218 nct02792231 keywords relapsing multiple sclerosis neurofilament light chain evidence disease activity progression independent relapse activity recently diagnosed treatmentnaive,0.0
manipulating level sensorimotor stimulation lirtms can improve visual circuit reorganisation adult ephrina2a5sup sup mice repetitive transcranial magnetic stimulation rtms noninvasive brain stimulation technique potential treat variety neurologic psychiatric disorders extent rtmsinduced neuroplasticity may dependent subjects brain state time stimulation chronic low intensity rtms lirtms previously shown induce beneficial structural functional reorganisation within abnormal visual circuits ephrina2a5 mice ambient,0.0
hydrogen ion dynamics fundamental link neurodegenerative diseases cancer application therapeutics neurodegenerative diseases special emphasis multiple sclerosis phrelated metabolic paradigm rapidly grown cancer research treatment contribution recent oncological perspective laterally assessed first time order integrate neurodegeneration within energetics cancer acidbase conceptual frame levels study molecular biochemical metabolic clinical intimate nature processes appears consist opposite mechanisms occurring far ends physiopathological,0.0
colaborativa platform based gamified collaborative practices prevent pressure injuries wheelchair users pressure injuries wounds caused reduced blood circulation regular repetitive periods pressing human body hard surface pathology needs daily preventive care health promotion avoid incidences thus article aims validate platform based gamified collaborative practices model prevent pressure injuries methodological contribution design science software evaluated 16 wheelchair users aimed,0.0
identification lowerlimb motor tasks via braincomputer interfaces topical overview recent engineering neuroscience applications led development braincomputer interface bci systems improve quality life people motor disabilities area significant number studies conducted identifying classifying upperlimb movement intentions contrary works concerned movement intention identification lower limbs notwithstanding lowerlimb neurorehabilitation major topic medical,0.0
prognostic markers multiple sclerosis multiple sclerosis ms chronic autoimmune disease high degree heterogeneity due course prognosis half ms patients discuss longterm prognosis doctor time patients consider importance personalized prognosis decisions family planning career medical interventions clinical markers used determine prognosis routine clinical practice however nominally divided positive,0.0
adultonset mild encephalitis encephalopathy reversible splenial lesion induced mrsa endocarditis background mild encephalitis encephalopathy reversible splenial lesion mers clinicoradiological syndrome unknown pathogenic mechanism usually involves children thus adultonset mers quite rare case presentation 71yearold man undergoing haemodialysis due diabetesinduced chronic kidney disease manifested persistent fever disorientation blood culture detected methicillinresistant staphylococcus aureus mrsa echocardiography revealed vegetation aortic mitral valves magnetic resonance imaging head revealed fluidattenuated inversion recoveryhigh diffusionweighted imagehigh lesion splenium corpus callosum number emboli accordingly patient diagnosed mers induced mrsa endocarditis discussion neurological impairment mers can reversible however differential diagnosis disease includes ischaemic lesions multiple sclerosis malignant lymphoma acute disseminated encephalomyelitis posterior reversible encephalopathy clinicians consider diseases mers suspected learning points adultonset mild encephalitis encephalopathy reversible splenial lesion mers quite rare physicians aware differential diagnosis diffusionweighted imagehigh lesion splenium corpus callosummethicillinresistant staphylococcus aureus mrsa rarely reported triggering factor mers keywords bacteraemia staphylococcus aureus corpus callosum infective endocarditis mild encephalitis encephalopathy reversible splenial lesion,0.0
rapid discrimination neuromyelitis optica spectrum disorder multiple sclerosis using machine learning infrared spectra sera neuromyelitis optica spectrum disorder nmosd multiple sclerosis ms autoimmune inflammatory demyelinating diseases central nervous system nmosd highly disabling disease rapid introduction appropriate treatment acute phase crucial prevent sequelae specific criteria established 2015 provide keys distinguish nmosd ms one reliable criteria nmosd diagnosis detection patients serum antibody,1.0
new halogencontaining drugs approved fda 2021 overview syntheses pharmaceutical use review describes recent food drug administration fda approved drugs year 2021 containing least one halogen atom covalently bound structures proposed throughout work grouped according therapeutical use synthesis presented well number halogenated molecules reaching market regularly preserved 14 50 molecules approved fda last year contain halogens underlines emergent role,0.0
vivo assessment ameliorative impact medicinal plant extracts lipopolysaccharideinduced multiple sclerosis wistar rats multiple sclerosis chronic autoimmune disorder leads demyelination nerve fibers major cause nontraumatic disability around world herbal plants nepeta hindustana l vitex negundo l argemone albiflora l addition antiinflammatory antioxidative effects shown great potential neuroprotective agents study aimed develop neuroprotective model study effectiveness herbal plants n hindustana v negundo,1.0
monoclonal antibody therapies beyond complement nmosd mogad aquaporin4 aqp4 igg seropositive neuromyelitis optica spectrum disorders aqp4igg seropositive nmosd myelin oligodendrocyte glycoprotein mog iggassociated disease mogad inflammatory demyelinating disorders distinct multiple sclerosis ms anticd20 treatments can used treat ms aqp4igg seropositive nmosd ms medications ineffective exacerbate aqp4igg seropositive nmosd including betainterferons natalizumab,1.0
fingolimod multiple sclerosis familial mediterranean fever coexistence background intriguing relationship familial mediterranean fever fmf multiple sclerosis ms fmf hereditary autosomal recessive disease characterized recurrent acute selflimited attacks fever polyserositis ms chronic inflammatory demyelinating disease central nervous system characterized autoreactive lymphocytes microglial activation chronic neurodegeneration patients suffering fmf ms interesting test whether treatments ms affect course fmf vice versa however interaction studied yet case presentation herein reported case fmf relapsingremitting ms fingolimod immunomodulatory oral ms therapy led nearcomplete resolution fmf symptoms conclusion report demonstrates interesting clinical observation may promise patients suffering ms fmf drugs effect course fmf needs research keywords familial mediterranean fever fingolimod multiple sclerosis,1.0
tumefactive demyelinating brain lesion developing administration adenovectorbased covid19 vaccine case report background postmarketing surveillance covid19 vaccination reveals covid19 vaccine administration associated several rare serious neurological complications case report report case newonset tumefactive demyelinating brain lesion developed administration adenovectorbased covid19 vaccine middleaged female presented recent right hemiparesis noticed 2 days received first dose vaccine magnetic resonance imaging mri revealed large subcortical t2 flair hyperintensities involving corpus callosum well patient responded oral methylprednisolone 4 weeks followup mri revealed reduction size lesion conclusion conclude adenovectorbased covid19 vaccination may associated tumefactive demyelinating lesion keywords acute disseminated encephalomyelitis brain tumor corticosteroids multiple sclerosis,1.0
lncrnamirna network analysis across th17 cell line reveals biomarker potency lncrna neat1 kcnq1ot1 multiple sclerosis differentiation cd 4+ t cells th17 cells important factor onset progression multiple sclerosis ms th17 treg imbalance little known role lncrnas differentiation cd 4+ cells th17 cells study aimed analyse lncrnamirnas network involved ms disease role differentiation th17 cells lncrnas th17 differentiation obtained gse66261 using geo datasets differential expression,0.0
crosssectional longitudinal correlations arm function multiple sclerosis questionnaire amsq outcome measures multiple sclerosis background arm function multiple sclerosis questionnaire amsq first validated disease specific patientreported outcome measure prom designed assess upper extremity function patients multiple sclerosis ms objective determine correlations amsq established physician performance based outcome measuresmethods crosssectional cohort 533 patients correlations amsq expanded disability status scale edss functional systems 9hole peg test 9hpt timed25 foot walk t25fw determined subgroup analyses performed well also correlations determined 110 533 patients available longitudinal dataresults strongest correlations found crosssectional cohort amsq edss 060 p001 9hpt dominant hand 052 p001 9hpt nondominant hand 046 p001 pyramidal 057 p001 cerebellar functional system 054 p001 edssconclusion moderate correlations amsq several established physician performance based outcome measures underline amsq easily longdistance administrable prom considered reliable outcome measure monitoring ms daily practice additional research needed support findings,0.0
regulating discriminatory response antigen t cell receptor cellmediated immune response constitutes robust host defense mechanism eliminate pathogens oncogenic cells tcells play central role defense mechanism creating memories prevent potential infection tcell recognizes foreign antigen surface receptors presented antigenpresenting cells calibrates cellular response network intracellular signaling events activation tcell receptor tcr leads changes gene expression,0.0
effect siponimod magnetic resonance imaging measures neurodegeneration myelination secondary progressive multiple sclerosis gray matter atrophy magnetization transfer ratio analyses expand phase 3 trial background magnetic resonance imaging mri measurements gray matter gm atrophy magnetization transfer ratio mtr correlate myelination may provide better insights conventional mri regarding brain tissue integrity myelination multiple sclerosis ms objective examine effect siponimod expand trial wholebrain gm atrophy newly formed normalized magnetization transfer ratio nmtr lesions nmtrassessed integrity normalappearing brain tissue nabt cortical gm cgm normalappearing white matter nawm methods patients secondary progressive multiple sclerosis spms received siponimod 2 mg day n 1037 placebo n 523 endpoints included percentage change baseline months 12 24 wholebrain cgm thalamic volumes change nmtr baseline months 12 24 nabt cgm nawm mtr recovery newly formed lesions results compared placebo siponimod significantly reduced progression wholebrain gm atrophy 12 24 months associated improvements brain tissue integrity myelination within newly formed nmtr lesions across nabt cgm nawm 24 months effects consistent across age disease duration inflammatory activity subgroups disease severity conclusion siponimod reduced brain tissue damage patients spms evidenced objective measures brain tissue integrity myelination consistent central nervous system cns effects observed preclinical models clinicaltrialsgov number nct01665144 keywords mri secondary progressive multiple sclerosis brain integrity gray matter magnetization transfer ratio myelination siponimod,1.0
effect functional electrical stimulation cycling exercise lower limb strength asymmetry persons multiple sclerosis background lower limb strength asymmetry ie significant difference contralateral limbs associated mobility impairment persons multiple sclerosis ms however whether adaptive exercise modality can used modify lower limb strength potentially improve mobility unclear effect functional electrical stimulation fes cycling lower limb strength asymmetry persons ms mobility impairment assessed association change lower limb strength asymmetries changes functional selfreported mobility outcomes explored methods eight adults ms expanded disability status scale scores 5565 included outcomes included knee extensor knee flexor strength asymmetry timed 25foot walk t25fw test 2minute walk test 2mwt timed go tug test 12item multiple sclerosis walking scale msws12 participants received 24 weeks 3 times per week fes cycling passive leg cycling results fes condition demonstrated small decrease knee extensor d 033 knee flexor d 023 strength asymmetry compared passive leg cycling groups combined weaktostrong associations observed change knee extensor asymmetry change t25fw test time rs 043 2mwt time rs 024 tug test time rs 055 msws12 score rs 043 moderate correlations observed change knee flexor asymmetry change t25fw test time rs 031 tug test time rs 033 msws12 score rs 035 conclusions fes cycling may efficacious exercise modality reducing lower limb strength asymmetry improving mobility persons ms keywords fes cycling strength assymetry,1.0
exploring selfmanagement needs persons multiple sclerosis qualitative study mobile application development background multiple sclerosis ms common cause neurologic disability young adults individuals ms deal daytoday effects disease lives selfmanagement can help challenges study aimed explore ms selfmanagement needs according experiences persons ms conducted part research project develop ms selfmanagement mobile application methods used qualitative method elicit selfmanagement needs among 12 individuals ms conducted semistructured interviews participants chosen based snowball sampling interviews recorded transcribed verbatim finally qualitative data analyzed using content analysis method inductive way identify underlying themes subthemes results analysis resulted emergence 7 themes source information basic needs understanding ms physical exercises ms useful nutrition ms ms monitoring communication within 7 themes identified 23 subthemes conclusions themes emerged study show needs essential help persons ms improve selfmanagement capacity findings can help development selfmanagement mobile applications supporting individuals managing ms keywords ms selfmanagement mobile app mobile application,0.0
progressive multifocal leukoencephalopathy risk perception patients considering natalizumab multiple sclerosis background progressive multifocal leukoencephalopathy pml remains concern considering natalizumab multiple sclerosis ms treatment extensive research identified factors increase pml risk important providers patients accurately understand risk make appropriate benefitrisk decisions methods one hundred adult us patientcandidates natalizumab therapy questioned pml risk perception maximum pml risk deemed acceptable sources information used understand risk differences group distributions compared results patients estimated potential pml risk 01 87 mean 315 maximum pml risk deemed acceptable ranged 01 45 mean 145 actual risk mean 001 based published risk estimates calculated function time receiving therapy antijohn cunningham virus antibody index previous use immunosuppressants sexes perceived risks similarly similar risk acceptance patient perception pml risk increased age whereas willingness accept risk remained similar among ages higher levels education correlated accurate risk perception lower risk tolerance neither risk perception tolerance correlated disability level sixtythree percent patients indicated primary referring physicians concern level regarding potential risk pml benefitrisk discussion main source information risk conclusions patients ms substantially overestimated pml risk often three orders magnitude patients ms benefit accurate risk education providers play essential role presenting pml risk information manner understandable individual patient keywords natalizumab pml progressive multifocal leukoencephalopathy,0.0
effects sensory interventions fatigue people multiple sclerosis systematic review background fatigue 1 common annoying symptoms patients multiple sclerosis ms purpose study investigate effect sensory interventions fatigue people ms based systematic review sensory evidence methods google scholar pubmed scopus cochrane library databases searched january 1990 july 2020 studies nonpharmacologic sensory interventions main secondary intervention according assessment fatigue primary secondary therapy outcome patients ms included results nine articles reviewed examining inclusion exclusion criteria four types interventions related exercises including sensory integration exercises vestibular rehabilitation frenkel exercises exercises without vibration 2 types performed using robots 1 type using vibration vestibular rehabilitation therapies exercisebased sensory integration interventions use vibration shown significant effects relieving fatigue patients ms conclusions evidence study insufficient show dramatic effect sensory integration therapy various forms however despite studies sensory integration therapy can considered potential treatment fatigue patients ms studies stronger methods needed make treatment reality keywords fatigue sensory intervention,0.0
demyelinating events following antitumor necrosis factor alpha therapy rare challenging treat conclusions findings suggest minority suspected demyelinating disease following tnfi fulfill diagnostic criteria ms ms diagnoses also among fulfilling ms criteria may contribute inflated epidemiological risk estimates nevertheless fulfilling ms criteria initiation disease modulating therapy escalation needed important suppress disease activity,1.0
recommendations address unique clinical psychological needs transgender persons living multiple sclerosis background people living multiple sclerosis ms face challenges coping chronic illnesses transgender tgd persons living ms may experience additional unique challenges barriers care medical biases toward tgd people widely reported best practices tgd ms care identified methods case report tgd person living ms reviewed helped identify inform us regarding unique aspects clinical psychological care needs conducted systematic review literature according standard methods pubmed literature reviewed summarized relevant topics related unique care needs tgd persons living ms proposed care recommendations created results used aforementioned case identify inform special care needs subsequently describe proposed recommendations achieve inclusive comprehensive care tgd persons ms importance providing inclusive environment comprehensive care mental health screening domestic violence screening case coordination highlighted goal providing best practice recommendations comprehensive inclusive care tgd persons living ms conclusions lack published guidance care tgd persons living ms informative case led proposed recommendations care tgd persons living ms keywords lgbtq transgender,0.0
bcelldepletion reverses dysbiosis microbiome multiple sclerosis patients elucidate crosssectional patterns longitudinal changes oral stool microbiota multiple sclerosis ms patients effect bcell depletion conducted observational longitudinal clinical cohort study analysing four timepoints 12 months 36 ms patients 22 initiated bcell depleting therapy ocrelizumab healthy control group microbiota analysis oral cavity gut provided stool oral swab samples underwent 16s rdna,0.0
analysis csf ddimer identify intrathecal fibrindriven autoimmunity patients multiple sclerosis background objectives proteins coagulation system contribute autoimmune inflammation patients multiple sclerosis ms bloodbrain barrier bbb disruption fibrinogen enters cns rapidly converted fibrin unfolding pleiotropic autoimmune mechanisms fibrin accumulation leads subsequent proteolytic degradation results ddimer generation primary objective study determine intrathecal levels ddimer csf measure,0.0
physical activity sedentary behavior patterns across weekdays weekend days youth multiple sclerosis controls background study quantified compared weekday weekend patterns devicemeasured physical activity pa sedentary behavior youth pediatric multiple sclerosis ms controls purpose informing future pa behavior change interventions methods participant data obtained 3 ongoing observational studies sample included 40 participants pediatric ms 41 controls light pa lpa moderate vigorous pa mvpa sedentary behavior data collected using activity monitors actigraph llc 1 week main analysis involved 2way mixed factor analysis variance group betweensubjects factor pediatric ms vs control day withinsubjects factor weekday vs weekend day results group day interaction analysis variance percentage activity monitor wear time spent lpa mvpa sedentary behavior effect group lpa mvpa sedentary behavior effect day week percentage day spent lpa mvpa sedentary behavior conclusions results suggest youth pediatric ms controls less physically active sedentary weekends weekdays differences groups pa sedentary behavior overall day week physical activity interventions may successful initially targeting weekend day activity keywords physical activity exercise pediatric multiple sclerosis sedentary behavior,0.0
diagnosis differential diagnosis misdiagnosis susac syndrome conclusions sus patients frequently misdiagnosed initial presentation despite many symptoms radiological features red flags diagnosis delayed diagnosis can lead patient morbidity varied ways sus can present clinician failure consider recognize sus appear main factors leading misdiagnosis,0.0
work participation multimodal rehabilitation due neurological diseases representative analyses using routine data german pension insurance conclusion half persons neurological diseases return sustainable work medical rehabilitation germany amount sick leave income rehabilitation determining factors whether person will return work analysis provides representative data occupational reintegration medical rehabilitation due neurological disease first time,0.0
epsteinbarr virus trigger ms abstract epsteinbarr virus ebv putative trigger multiple sclerosis ms clear causality lacking recent issue science bjornevik cortese et al utilize longitudinal evaluation 10 million adults demonstrate increased ms risk ebv infection,0.0
tools comprehensive evaluation sexual function patients multiple sclerosis abstract introduction multiple sclerosis ms demyelinating disease central nervous system cns affects young adults causing variety symptoms motor alterations visual alterations loss sphincter control gait alterations impair patients functional status however symptoms sexual dysfunction can also effect quality life development sexual dysfunction can occur time course disease prevalence varies 50 90 can secondary demyelinating lesions spinal cord brain caused symptoms directly involve nervous system fatigue psychological social cultural factors etc although prevalence impact quality life well known sexual dysfunction still frequently underestimated therefore article review different scales assessing presence severity sexual dysfunction order offer early multidisciplinary management conclusion evaluated 5 questionnaires identify presence sexual dysfunction patients ms determine aetiology assisting treatment decision making ms must understood complex disease encompasses compromises different aspects patients health goes beyond simply measuring disability keywords calidad de vida depresin depression disability discapacidad disfuncin sexual esclerosis mltiple funcin urodinmica multiple sclerosis quality life sexual dysfunction urodynamic function,1.0
validity reliability scale report emotional stress signsmultiple sclerosis stressms assessing abuse neglect adults multiple sclerosis background approximately 30 people multiple sclerosis ms require caregiving unknown prevalence abuse neglect explore issues created scale report emotional stress signsmultiple sclerosis stressms objective develop validate fieldtest selfreport questionnaire screening people ms mistreatment methods developed stressms questionnaire administered 102 adults advanced msrelated disability 97 primary informal caregivers correlating responses direct observation mistreatment conducting item analysis evaluating validity using longitudinal expert data lead panel results stressms subscales correlated highly criterionstandard lead panel evaluations mistreatment strong concurrent discriminant validity nearly 53 participants ms reported experiencing psychological abuse 98 financial exploitation 69 physical abuse 49 neglect 39 sexual abuse protective factors people ms included social support older age risk factors included depression aggressiveness greatest risk factor informal caregiver spent 20 hours per week caring person ms conclusions stressms questionnaire reasonably reliable valid detecting caregiver mistreatment adults ms although informal caregivers abusive study highlights underrecognized need detect prevent abuse neglect people ms keywords stressms stress,0.0
immunosenescence role age multiple sclerosis conclusions number older people ms increasing due population ageing advances diseasemodifying treatments improved health social care patients ageing immune system increases risk infections tumours autoimmune diseases elderly individuals furthermore neurodegeneration accelerated patients ms due nervous systems loss remyelination capacity understanding changes affecting immune system,1.0
remote assessments hand function neurological disorders systematic review conclusions findings show remote assessment hand function feasible neurological disorders although varied assessments allow clinicians objectively record performance multiple hand function domains improving reliability traditional inclinic assessments remote assessments particularly via telerehabilitation smartphone tabletbased apps align inclinic metrics facilitate clinic home transitions barriers implementation,0.0
systematic overviews partnership principles strategies identified health research spinal cord injury related health conditions scoping review conclusion provided systematic overviews principles strategies research partnerships used researchers research users want work partnership plan conduct disseminate sci research findings informed development new sci integrated knowledge translation guiding principles wwwiktprinciplescom will support implementation principles within sci research system,0.0
quantitative susceptibility mapping versus phase imaging identify multiple sclerosis iron rim lesions demyelination abstract background purpose compare quantitative susceptibility mapping qsm highpassfiltered hpf phase imaging 1 identifying chronic active rim lesions myelin damage 2 distinguishing patients increased clinical disability multiple sclerosis methods eighty patients scanned qsm paramagnetic rim detection fast acquisition spiral trajectory t2prep myelin water fraction mwf chronic lesions classified based presence absence rim hpf qsm images lesionlevel linear mixedeffects model mwf outcome used compare myelin damage among lesion groups multiple patientlevel linear regression model fit establish association expanded disease status scale edss log number rim lesions results 2062 lesions 188 91 hpf rim+ qsm rim+ 203 98 hpf rim+ qsm rim remainder rim linear mixedeffects model hpf rim+ qsm rim+ lesions significantly lower mwf hpf rim+ qsm rim p 001 hpf rim qsm rim p 001 lesions mwf difference hpf rim+ qsm rim hpf rim qsm rim lesions statistically significant p 130 holding factors constant log number qsm rim+ lesion associated edss increase p 044 association log number hpf rim+ lesions edss statistically significant p 206 conclusions qsm identifies paramagnetic rim lesions average myelin damage stronger association clinical disability detected phase imaging keywords chronic active lesions highpassfiltered phase imaging multiple sclerosis myelin water fraction mwf paramagnetic rim quantitative susceptibility mapping qsm,1.0
unique features central neuropathic pain multiple sclerosis results cluster analysis background central neuropathic pain cnp excruciating condition prevalent third patients multiple sclerosis ms identifying cnp among ms patients particularly challenging considering ample comorbid chronic pain conditions sensory disturbances entailed disease aim identify sensory features unique cnp beyond chronic pain ms methods participants 112 ms patients 44 diagnosis cnp 28 diagnosis chronic musculoskeletal pain msp 40 painfree participants underwent testing thermal mechanical thresholds thermal grill illusion tgi pain adaptation pa offset analgesia oa chronic pain characterized twostep cluster analysis performed association cluster membership clinical group membership cnp msp painfree evaluated results cnp msp groups similar chronic pain variables eg severity location quality msrelated variables eg type severity medication intake three created clusters unique sensory features 1 hyposensitivity increased thermal touch thresholds characterized cnp group 2 poor inhibition hyperalgesia worst pa oa decreased tgi threshold characterized msp group 3 efficient inhibition best pa oa smallest sensory loss characterized painfree group conclusions unique sensory features cnp msp provide insight pathophysiology evaluating may increase ability provide individuallybased interventions efficient inhibition may protect ms patients chronic pain keywords multiple sclerosis qst central neuropathic pain cluster analysis,0.0
failure alemtuzumab therapy three patients mog antibody associated disease background myelin oligodendrocyte glycoprotein antibodyassociated disease mogad classically associated children adults phenotypes including bilateral recurrent optic neuritis transverse myelitis tm absence brain lesions characteristic multiple sclerosis ms adem phenotype common presentation mogad children however presence clinical phenotypes including unilateral short tm patients mogad may lead misdiagnosis ms thus clinically radiologically mogad can mimic ms clinical vigilance required accurate diagnostic workupcase presentationwe present three cases initially diagnosed ms treated alemtuzumab unexpectedly three patients quite poorly medication decline clinical status worsening expanded disability status scale edss increasing lesion load magnetic resonance imaging brain subsequently three cases found antimog antibody serumconclusionsthese cases highlight patient suspected ms respond conventional treatments alemtuzumab search alternative diagnoses mog antibody disease may warranted,1.0
pharmacological treatment tremor multiple sclerosis systematic review backgroundtremor relatively common symptom multiple sclerosis ms can negatively affect several aspects patients life one disabling symptoms ms pharmacological treatment msrelated tremor studied several years though treatment still challenging study will review studies pharmacological treatment tremor ms update treatment recommendationsmethodsany relevant englishlanguage clinical trial investigated pharmacological treatment msrelated tremor adults eligible study searched medline pubmed scopus embase web science bias assessment performed casp critical appraisal skills programme checklist methods followed prisma guidelinesresultsthe initial search resulted 3024 articles 26 articles included eligible studies 13 articles low risk bias remained full manuscript review results studies 5ht3 receptor antagonists single dose treatment inconsistent botulinum toxin significant effects msrelated tremor adverse effects injection procedures limited application application cannabisbased medicine treat msrelated tremor recommended due inconclusive therapeutic effects several side effects levetiracetam inconsistent results antiepileptic drugs studied precisely isoniazid minor therapeutic effects possible adverse effects treatment msrelated tremorconclusionfurther welldesigned comparative clinical trials large sample size can improve clinical management tremor patients ms,0.0
health related quality life among pregnant women living hiv kenya results comparing patient generated index euroqol 5 dimension 3 level background standardized tools used measure healthrelated quality life hrqol focus selected physical emotional social functioning approach may miss heterogeneity hrqol among various subpopulations patientgenerated index pgi tool used measure hrqol based patients expectations among patients living hiv hrqol important indicator world moves beyond unaids 909090 goals towards socalled fourth 90 aims good hrqol compared pgi euroqol 5 dimension 3level eq5d3l identify areas importance pregnant women living hiv affecting thier hrqolmethodsthrough convenience sampling surveyed 100 pregnant women living hiv attending antenatal postnatal clinics western kenya using pgi eq5d3l questionnaires pgi score eq5d3l index generated participant data pgi also summarized themes pgi scores eq5d3l index scores correlated using pearson correlationresultsfrom pgi tool 64 women reported two three main priority areas lives affected hiv status areas centered themes economic wellbeing 84 women physical health 58 psychological emotional health 49 relationships 28 mean pgi score 201 sd 110 median 110 majority women reported problems 5 dimensions captured eq5d3l mean eq5d3l score 094 sd 110 median 100 eq5d3l pgi showed less perfect hrqol correlation pgi eq5d3l scoresconclusionthe pgi may capture aspects contextual social emotional life kenyan pregnant women living hiv identified generic tools highlighting areas importance patients hrqol key focus shifts towards fourth 90 may also inform design care programs aligned patient needs,0.0
oligomers trigger necroptosismediated neurodegeneration via microglia activation alzheimers disease abstractalzheimers disease ad major adultonset neurodegenerative condition available treatment compelling reports point amyloid main etiologic agent triggers ad although extensive evidence detrimental crosstalk microglia contributes neuroinflammation ad exact mechanism leading neuron death remains unknown using postmortem human ad brain tissue show pathology associated necroptosis effector pmlkl moreover found burden oligomers ao correlates expression key markers necroptosis activation additionally inhibition necroptosis pharmacological genetic means reduce neurodegeneration memory impairment triggered ao mice since microglial activation emerging central driver ad pathogenesis tested contribution microglia mechanism aomediated necroptosis activation neurons using vitro model show conditioned medium aostimulated microglia elicited necroptosis neurons activation tnf signaling triggering extensive neurodegeneration notably necroptosis inhibition provided significant neuronal protection together findings suggest aomediated microglia stimulation ad contributes necroptosis activation neurons neurodegeneration necroptosis druggable degenerative mechanism findings might important therapeutic implications prevent progression ad,0.0
fluid shear stress enhances t cell activation piezo1 background t cell activation mechanical process much biochemical process study used coneandplate viscometer system treat jurkat primary human t cells fluid shear stress fss enhance activation t cells mechanical meansresultsthe fss treatment t cells combination soluble beadbound cd3 cd28 antibodies increased activation signaling proteins essential t cell activation zetachainassociated protein kinase70 zap70 nuclear factor activated t cells nfat nuclear factor kappa b nfb ap1 activator protein 1 fss treatment also enhanced expression cytokines tumor necrosis factor alpha tnf interleukin 2 il2 interferon gamma ifn necessary sustained t cell activation function enhanced activation t cells fss calcium dependent calcium signaling controlled mechanosensitive ion channel piezo1 gsmtx4 piezo1 knockout reduced zap70 phosphorylation fssconclusionsthese results demonstrate intriguing new dynamic t cell activation circulatory system consists different magnitudes fss proinflammatory role t cell function results also identify potential pathophysiological relationship t cell activation fss hypertension disease characterized abnormal blood flow correlated multiple autoimmune diseases,0.0
impaired functional network properties contribute white matter hyperintensity related cognitive decline patients cerebral small vessel disease background white matter hyperintensity wmh one typical neuroimaging manifestations cerebral small vessel disease csvd wmh correlates closely cognitive impairment ci csvd patients wmh altered topological properties brain functional network possible mechanism leads ci study aims identify differences characteristics brain functional network among patients different grades wmh estimates correlations different brain functional network characteristics cognitive assessment scoresmethods110 csvd patients underwent 30 t magnetic resonance imaging scans neuropsychological cognitive assessments wmh participant graded basis fazekas grade scale divided two groups wmh score 12 points n 64 b wmh score 36 points n 46 topological indexes brain functional network analyzed using graphtheoretical method ttest mannwhitney u test used compare differences topological properties brain functional network groups partial correlation analysis applied explore relationship different topological properties brain functional networks overall cognitive functionresultspatients high wmh scores exhibited decreased clustering coefficient values global local network efficiency along increased shortest path length whole brain level well decreased nodal efficiency brain regions nodal level p 005 nodal efficiency left lingual gyrus significantly positively correlated patients total montreal cognitive assessment moca scores p 005 significant difference found two groups aspect total moca minimental state examination mmse scores p 005 conclusiontherefore come conclusions patients high wmh scores showed less optimized smallworld networks compared patients low wmh scores global local network efficiency wholebrain level well nodal efficiency certain brain regions nodal level can viewed markers reflect course wmh,0.0
controlled human malaria infections mosquito bites induce severe clinical symptoms asexual bloodstage challenge infections backgroundfever inflammation hallmark clinical plasmodium falciparum pf malaria induced circulating asexual parasites although clinical manifestations inflammation associated parasite density relationship influenced complex network immunemodulating factors human parasite originmethodsin controlled human malaria infection chmi model compared clinical inflammation healthy malarianave volunteers infected either pfinfected mosquito bites mb n12 intravenous administration pfinfected red blood cells bs n12 findingsall volunteers developed patent parasitaemia incidence duration severe adverse events significantly higher mb infection similarly clinical laboratory markers inflammation significantly increased mbgroup well serum proinflammatory cytokine concentrations including ifn il6 mcp1 il8 parasite load reflected maximum parasite density area curve similar median duration parasitaemia treatment longer bsgroup compared mbgroup 8 days range 8 8 days versus 55 days range 35 125 days vitro response subsets peripheral blood mononuclear cells showed attenuated pfspecific ifn production tcells bsarminterpretationin conclusion irrespective parasite load pfinfections mb induce stronger signs symptoms inflammation compared chmi bs infection pathophysiological basis remains speculative may relate induced immune tolerancefundingthe trial supported paths malaria vaccine initiative current analyses supported ammodo science award 2019 tb,0.0
development translational inflammation panel quantification cerebrospinal fluid pterin tryptophankynurenine nitric oxide pathway metabolites backgroundneuroinflammatory diseases encephalitis meningitis multiple sclerosis neurological diseases inflammatory components demonstrated need diagnostic biomarkers define treatable reversible neuroinflammation development clinical validation targeted translational inflammation panel using liquid chromatography coupled tandem mass spectrometry lcms ms provide early diagnosis rapid treatment insights neuroinflammatory mechanismsmethodsan inflammation panel 13 metabolites neopterin tryptophan kynurenine kynurenic acid 3hydroxykynurenine xanthurenic acid anthranilic acid 3hydroxyanthranilic acid quinolinic acid picolinic acid arginine citrulline methylhistamine measured based simple precipitation filtration method using minimal csf volume chromatographic separation achieved using acquity uplc beh c18 column combination gradient elution within 12min time frame acute encephalitis n10 myelin oligodendrocyte glycoprotein encephalitis n3 antinmethyldaspartate encephalitis n2 acute disseminated encephalomyelitis n2 herpes simplex encephalitis n1 enteroviral encephalitis n1 frequencymatched noninflammatory neurological disease controls n10 examinedfindingsthe method exhibited good sensitivity limits quantification ranged 075 300 ng ml1 good linearity r 2 099 acceptable matrix effects 194 high recoveries 8981091 interferences observed common endogenous csf metabolites carryover concordance wellestablished clinical methods accuracy precision analytes within tolerances 15 mean relative error 15 coefficient variation respectively analytes matrixmatched pooled human csf calibrators human csf extracts stable 24 h extraction two freezethaw cyclesinterpretationthe method successfully applied pilot study investigating acute brain inflammation casecontrol groups statistical discrimination encephalitis n10 control groups n10 achieved using orthogonal partial least squares discriminant analysis heatmap cluster analysis statistical analysis measured metabolites identified significant alterations seven metabolites tryptophankynurenine pathway tryptophan kynurenine kynurenic acid 3hydroxykynurenine anthranilic acid 3hydroxyanthranilic acid quinolinic acid arginine neopterin presence acute neuroinflammation furthermore elevated ratios csf kynurenine tryptophan ratio quinolinic acid kynurenic acid anthranilic acid 3hydroxyanthranilic acid provided strong discriminative power neuroinflammatory conditions studies large groups neurological diseases required explore sensitivity specificity inflammation panelfundingfinancial support study granted dale nhmrc investigator grant app1193648 petre foundation cerebral palsy alliance department biochemistry childrens hospital westmead,1.0
development evaluation evidencebased patient information handbooks multiple sclerosis immunotherapies backgroundmultiple sclerosis treatment options increasing evidencebased patient information ebpi therefore crucial enable patient involvement decision making based earlier work decision support patient information handbooks 8 ms immunotherapies developed piloted evaluated support german clinical competence network ms german ms societymethodshandbooks structured according ebpi concepts drafts commented patient representatives neurologists ms expertise executive boards german ms society competence network well pharmaceutical companies feedback included handbooks distributed among ms neurologists german ms society evaluation followed applying mixed methods approach interviews focus groups surveys one survey addressed persons ms pwms based questionnaire included handbook neurologists received printed patient handbooks invited give feedback second surveyresultseight handbooks developed providing absolute relative risk information numbers figures well monitoring needs drug fact boxes despite high amount information display low absolute risk reduction rates treatments handbooks overall appreciated pwms n107 mostly also physicians n24 70 pwms information new understandable supportive decision making patients felt uncomfortable relative risk information however response rates evaluation low exposing challenges implementing ebpi clinical care therefore conclusions must considered preliminarilyconclusionebpi immunotherapies ms seem feasible appreciated patients treating neurologists implementation research needed,0.0
neuroimmunometabolism new pathological nexus underlying neurodegenerative disorders neuroimmunometabolism emerging field examines intersection immunological metabolic cascades brain neuroinflammatory conditions often involve differential metabolic reprogramming neuronal glial cells immunometabolic sensors impact bioenergetic adaptation general brain function poorly understood crosstalk becomes increasingly important neurodegenerative disorders exhibit reshaping neuroimmunometabolic pathways summarize intrinsic balance neuroimmunometabolic substrates sensors healthy brain dysregulation can contribute pathophysiology various neurodegenerative disorders review also proposes possible avenues disease management neuroimmunometabolic profiling therapeutics bridge translational gaps guide future treatment strategiessignificance statementneuroimmunometabolism intersects neuroinflammation immunometabolic regulation neurons glial cells cns emerging evidence neuroimmunometabolism plays essential role manifestation cns degeneration review highlights neuroimmunometabolichomeostasis disrupted various neurodegenerative conditions target new therapeutic strategies,0.0
vulvovaginal pyoderma gangrenosum patient treated ocrelizumab multiple sclerosis abstract,0.0
longitudinal relationships disability gait characteristics people ms longitudinal data vital order understand intra individual gait changes progression multiple sclerosis ms therefore primary aim study explore relationship changes disability changes major spatiotemporal parameters gait people ms pwms pwms n 83 completed two gait assessments performed separate time points m1 m2 individual absolute difference expanded disability status scale,0.0
abcb1 gene variants risk factors modulators age onset demyelinating disease mexican patients abstract introduction c1236t g2677t c3435t variants abcb1 gene alter functioning pglycoprotein transport endogenous exogenous substances across bloodbrain barrier act risk factors neurodegenerative diseases study aimed determine association demyelinating disease c1236t g2677t c3435t variants abcb1 haplotypes combinations genotypes methods polymerase chain reaction restriction fragment length polymorphism analysis pcrrflp sanger sequencing used genotype 199 patients demyelinating disease 200 controls mexicans mixed race frequencies alleles genotypes haplotypes genotype combinations compared patients controls conducted logistic regression analysis calculated chisquare values 95 confidence intervals ci odds ratios calculated evaluate association demyelinating disease results ttt cgc haplotypes frequent patients controls g2677 allele associated demyelinating disease 179 95 ci 112286 p 015 genotypes gg2677 272 95 ci 111668 p 025 cc3435 182 95 ci 115290 p 010 combination gg2677 cc3435 202 95 ci 117348 p 010 cat haplotype 021 95 ci 005066 p 001 tttttt carriers presented earliest age onset 230 77 years vs 316 107 p 0001 conclusions gg2677 cc3435 genotype combination associated demyelinating disease sample particularly among men may present toxic accumulation pglycoprotein substrates study g2677 allele abcb1 may differentially modulate age onset demyelinating disease men women keywords abcb1 gene anlisis de asociacin anlisis de haplotipos association analysis demyelinating disease enfermedad desmielinizante esclerosis mltiple gen abcb1 glicoprotena p haplotype analysis multiple sclerosis pglycoprotein,1.0
magnetic resonance imaging primary progressive multiple sclerosis patients review recently developed effective treatment primary progressive multiple sclerosis ppms requires accurate diagnosis patients type disease currently diagnosis ppms based 2017 mcdonald criteria although contribution magnetic resonance imaging mri process fundamental ppms one clinical types ms represents 1015 ms patients compared relapsingremitting ms rrms ppms differs terms pathology clinical,0.0
prevalence disability improvement relapsingremitting multiple sclerosis patients treated cladribine tablets background show application prevalence estimator expanded disability status scale edss improvement time patients treated cladribine tablets phase iii clarity clarity extension trials methods evaluated relapsingremitting ms patients entered clarity extension study patients originally randomized clarity cladribine tablets 35 mg kg placebo clarity extension early cladribine ec compared patients originally randomized placebo assigned cladribine tablets 35 mg kg delayed cladribine dc ec compared dc group prevalence edss improvement time cumulative incidence edss improvement prevalence improvement assessed new approach based difference kaplanmeier km estimators incidence improvement assessed standard km curves results total 98 patients ec group 244 patients dc group compared patients ec group showed significantly higher p0011 prevalence improvement year 2 ec 213 95ci 136293 dc 89 95ci 55128 year 5 ec 157 95ci 82237 dc 83 95ci 45124 cumulative incidence improvement also significantly different hr 182 95ci113294 p0013 conclusions assessment prevalence edss improvement alternative outcome assess treatment induces maintain improvement long term estimator resulted powerful cumulative incidence improvement detect treatment effect cladribine vs placebo 5 years keywords cladribine disability improvement edss prevalence longterm,0.0
acute effects axial loading postural control walking turning people multiple sclerosis pilot study background impaired sensory integration heavily involved gait control accentuates fall risk individuals multiple sclerosis ms axial loading found beneficial little known effect nonspecific axial loads gait parameters mobility tasks ms research question effects nonspecific axial loading via weighted vests walking turning ms methods twelve participants ms eleven age gendermatched healthy controls participated crosssectional study participants completed five trials continuous walking turns wearing weighted vests 0 2 4 5 0 body weight gait parameters measured using wireless inertial sensors 2 group x 5 vest weight multivariate analysis variance manova performed determine significant differences groups across weighted vests gait variable posthoc analysis paired ttests corresponding effect sizes also conducted results significant groups main effect found group f 6100 1474 p 000 multiple gait parameters p 005 although significant main effect found weighted vest within group analyses indicated significantly increased cadence gait speed across varying weighted vests ms control groups p 0 05 increased vest weight 0pre 2 also large effect shortening double support time increasing stride length ms group significance study provided preliminary evidence nonspecific axial loads varying weights appear improve certain gait parameters modality may offer mobility benefit serve accessible homebased intervention alternative aimed improving walking individuals ms keywords balance gait multiple sclerosis sensory modulation torso weighting,0.0
shining light clinical application mesenchymal stem cell therapy autoimmune diseases autoimmune diseases associated host immune system chronic inflammation immune reaction selfantigens leads injury failure several tissues onset autoimmune diseases related unbalanced immune homeostasis mesenchymal stem cells mscs multipotent cells capability selfrenew differentiate various cell types exert critical role immunomodulation regenerative therapy certain condition,0.0
antibiotic treatment pregnancy lactation dams exacerbates clinical symptoms inflammatory responses offspring experimental autoimmune encephalomyelitis growing body evidence demonstrates imbalance intensive communication gut microbiota host might associated immunerelated disorders multiple sclerosis study set determine whether antibiotic treatment pregnancy lactation can affect onset severity clinical symptoms inflammatory responses offspring experimental autoimmune encephalomyelitis eae mouse model multiples sclerosis female c57bl 6,0.0
microstructural white matter abnormalities multiple sclerosis neuromyelitis optica spectrum disorders evaluation advanced diffusion imaging abstract introduction despite differences pathogenesis treatment multiple sclerosis ms neuromyelitis optica spectrum disorders nmosd remains difficult distinguish study aimed discriminate ms nmosd using diffusion tensor imaging dti free water fw imaging neurite orientation dispersion density imaging noddi methods thirty patients relapsingremitting rr ms 18 nmosd patients positive antiaquaporin4 immunoglobulin g seroreactivity 20 age sex matched currently healthy subjects underwent mri differences dti fractional anisotropy fa axial diffusivity ad mean diffusivity md radial diffusivity rd fw fwcorrected dti noddi indices three groups evaluated using tractbased spatial statistics tbss regionofinterest roi analyses results roi analysis lesions indicated rrms group significantly higher ad md rd iso fwcorrected ad md lower intracellular volume fraction icvf nmosd group tbss analysis showed increased water content rrms patients compared nmosd patients compared healthy controls hcs using tbss roi analysis changes fw imaging indices limited dti rrms patients conclusion fw imaging noddi useful identifying etiology neurodegeneration neuroinflammationrelated microstructural changes rrms nmosd patients keywords diffusion tensor imaging free water imaging multiple sclerosis neurite orientation dispersion density imaging neuromyelitis optica spectrum disorders tractbased spatial statistics,0.0
clinical worsening following discontinuation tocilizumab diffuse cutaneous systemic sclerosis singlecentre experience japan abstract objective investigate outcomes following tapering discontinuation tocilizumab patients diffuse cutaneous systemic sclerosis dcssc realworld setting methods fifteen patients treated tocilizumab dcssc selected singlecentre cohort database evaluated serial changes modified rodnan total skin thickness score mrss predicted forced vital capacity fvc occurrence clinical worsening events introduction tocilizumab results 12 months treatment tocilizumab mrss decreased 204 107 123 85 p 0003 fvc increased 843 137 885 164 p 004 tocilizumab tapered discontinued 7 3 patients respectively improvement skin thickening without occurrence progression organ manifestations one 14 7 patients underwent tocilizumab tapering experienced worsening skin thickening 3 patients discontinued tocilizumab experienced worsening skin thickening new development pericarditis arthritis interstitial lung disease ild pulmonary arterial hypertension additional patient discontinued tocilizumab due adverse event experienced subsequent progression multiple organ manifestations including skin lung lower gastrointestinal renal involvement leading mortality conclusion findings suggest potential benefits prolonged tocilizumab use dcssc patients discontinuation tocilizumab can lead progression skin visceral manifestations tapering rather discontinuation tocilizumab viable option dcssc patients experience remarkable clinical improvement keywords il6 scleroderma systemic sclerosis interstitial lung disease tocilizumab,0.0
costeffectiveness budget impact analysis siponimod treatment secondary progressive multiple sclerosis italy background siponimod effective treatment patients secondary progressive multiple sclerosis spms active disease evidenced relapses imaging features characteristic multiple sclerosis inflammatory activity however need evaluate economic value sustainability compared disease modifyingtherapies dmts objective estimate siponimod costeffectiveness profile relative budget impact compared dmts using italian national healthcare system perspective methods performed 1 costeffectiveness analysis cea vs interferon beta1b using analytical markov model life timehorizon 2 budget impact analysis using 3years timehorizon results reported incremental costeffectiveness ratio icer netmonetary benefit nmb cea using willingness pay threshold 40 000 per qaly gained difference overall budget euro scenario without siponimod budget impact results base case scenario siponimod resulted costeffective compared interferon beta1b 28 891 per qaly overall market access siponimod associated increased budget 3 millions +09 next 3 years simulated conclusion compared interferon beta1b siponimod seems costeffective spms patients sustainable less 1 overall budget increased next 3 years future studies need confirm results real word setting countries,0.0
attentional networks neurodegenerative diseases anatomical functional evidence attention network test conclusions anatomical structures proposed 3 attentional networks model confirmed relevant structures alertness network prefrontal cortex parietal region thalamus cerebellum thalamus also relevant orienting network together posterior parietal regions executive network depend exclusively prefrontal cortex anterior cingulate cortex also involves subcortical structures basal,0.0
anaesthetic management child west syndrome associated tuberous sclerosis complex remote location case report west syndrome rare syndrome consists triad infantile spasms hypsarrhythmia pattern electroencephalogram mental retardation tuberous sclerosis complex tsc one disorders can cause radiology suites considered remote locations anaesthesiologists delivery anaesthesia becomes challenging patient rare disease multiple anaesthetic implications arrives present anaesthetic management radiological,0.0
coronaviruses relationship multiple sclerosis prevalence multiple sclerosis going increase covid19 pandemia purpose review examine whether possible etiological triggering relationship infection various coronaviruses including severe acute respiratory syndromerelated coronavirus2 sarscov2 virus responsible coronavirus disease19 covid19 pandemia multiple sclerosis ms whether increase prevalence ms current covid19 pandemia expected examining new preexisting data although exact,0.0
meniscal anterior posterior horn heights associated mridefined knee structural abnormalities middleaged elderly patients symptomatic knee osteoarthritis background meniscal morphological changes associated knee oa however correlation meniscal height oarelated knee structural abnormalities still well understood purpose present study investigate whether meniscal anterior posterior horn heights associated structural abnormalities knees symptomatic oamethodsour sample consisted 106 patients 61 female aged 4073 years symptomatic knee oa kellgrenlawrence system used radiographic evaluation sagittal sequence medial meniscal posterior horn height mph lateral meniscal anterior horn height lah lateral meniscal posterior horn height lph measured middle slice medial lateral compartment knee structural abnormalities assessed using modified wholeorgan magnetic resonance imaging score worms associations meniscal anterior posterior horn heights knee structural abnormalities assessed using linear regression analysisresultshigher mph significantly associated higher worms score medial meniscal anterior horn lesion p 0016 statistical association worms parameters increased lah statistically correlated decreased worms scores lateral compartmental cartilage lesions p 00010004 lateral compartmental bone marrow edema patterns bmeps p 00210027 moreover lph negatively associated worms scores lateral compartmental cartilage lesions p 00070041 lateral compartmental bmeps p 00220044 additionally higher mph statistically associated lower trochlea cartilage worms score higher lah significantly correlated higher worms score trochlea subarticular cystsconclusionschanges lah lph inversely associated severity lateral compartmental cartilage lesions bmeps higher mph significantly correlated severe medial meniscal anterior horn lesions besides mph lah also significantly associated patellofemoral structural abnormalities present study provided novel information understanding role meniscal morphological changes knee oa helpful identifying evaluating knees risks oa,0.0
multicenter study evaluate disease burden health economics inpatients multiple sclerosis china abstractobjectiveto assess disease burden health economics inpatients multiple sclerosis ms china evaluating direct indirect intangible costsmethodsa total 863 patients included crosssectional retrospective study 50 centers direct economic burden measured cost hospitalization outofhospital application drugs indirect economic burden measured human capital method disabilityadjusted life year daly used express intangible economic burden costutility analysis cua using dalys indicators health benefits performed calculating incremental costutility ratioresultsthe mean direct economic burden year daily medication expenses year daly indirect economic burden indirect economic burden year 2765557 yuan 1794497 yuan 1089 yuan 5120417 yuan 1129985 yuan respectively study period two years direct economic burden daily medication expense indirect economic burden 486 315 1985 total economic burden respectively disease burden number episodes remission statistically significant p0001 direct economic burden total economic burden diseasemodifying therapy dmt group higher nondmt group dalys statistical significance p0001 cua showed inpatients ms dmt group received daly every time compared nondmt groupconclusionthe daly losses concentrated young middleaged chinese people twoyear study cua prompted application dmt drugs increase economic burden dalys however followup time still short followup observation required,0.0
polymorphism rs12294045 eaat2 gene potentially associated schizophrenia chinese han population background recent studies shown excitatory amino acid transporters eaats associated schizophrenia aim study investigate relationship polymorphism eaat1 eaat2 genes schizophrenia chinese han populationmethodsa total 233 patients schizophrenia 342 healthy controls enrolled two snps eaat1 gene rs2269272 rs2731880 four snps eaat2 gene rs12360706 rs3088168 rs12294045 rs10836387 genotyped snapshot clinical features collected using selfmade questionnaire psychotic symptoms patients measured positive negative syndrome scale panss patients cognitive function assessed matrics consensus cognitive battery mccb resultssignificant difference allelic distributions cases controls confirmed locus rs12294045 0004 eaat2 gene different genotypes rs12294045 associated family history p 0046 patients ct genotype higher proportion family history psychosis polymorphism rs12294045 related working operational memory lns p 0016 verbal learning function hvltr p 0042 patients ct genotype lower scores however differences longer significant bonferroni correctionconclusionsour study showed polymorphism rs12294045 eaat2 gene may associated schizophrenia chinese han population ct genotype may one risk factors family history cognitive deficits patients,0.0
neurodegenerative disease landscape rare mutations colombia due founder effects background colombian population well latin american regions arose recent tricontinental admixture among native americans spanish invaders enslaved africans passed population bottleneck due widespread infectious diseases left small isolated local settlements result current population reflects multiple founder effects derived diverse ancestriesmethodswe characterized role admixture founder effects origination mutational landscape led neurodegenerative disorders historical circumstances genomes 900 colombian individuals alzheimers disease ad n 376 frontotemporal lobar degenerationmotor neuron disease continuum ftldmnd n 197 earlyonset dementia otherwise specified eod n 73 healthy participants n 254 analyzed examined global local ancestry proportions screened cohort deleterious variants diseasecausing riskconferring genesresultswe identified 21 pathogenic variants adftld related genes psen1 harbored majority 11 pathogenic variants variants identified three continental ancestries trem2 heterozygous homozygous variants common among ad risk genes 102 carriers point interest disease risk conferred variants differed according ancestry several gene variants known association mnd european populations ftld phenotypes native american haplotype consistent founder effects identity descent among carriers variant frequentconclusionscolombian demography multiple minibottlenecks probably enhanced detection founder events left proportionally higher frequency rare variants derived ancestral populations findings demonstrate role genomically defined ancestry phenotypic disease expression phenotypic range different rare mutations gene emphasize importance inclusiveness genetic studies,0.0
familial multiple sclerosis patients von hippellindau disease background multiple sclerosis ms progressive autoimmune demyelinating disorder recent studies suggest combination genetic susceptibility environmental insult contributes pathogenesis many candidate genes discovered modulate susceptibility developing ms genome wide association studies gwas include major histocompatibility complex mhc genes nonmhc genes ms cases context genetic diseases may provide different approaches clues towards identifying novel genes pathways involved ms pathogenesis present case series two related patients concomitant von hippellindau disease vhld mscase presentationwe present two patients mother case 1 daughter case 2 developed superimposed relapsingremitting multiple sclerosis background autosomal dominant genetic disorder vhld several tumors characteristic vhld developed cases pancreatic renal neoplasms cerebellar hemangioblastomas addition patients developed clinical symptoms consistent multiple sclerosis supported radiologic lesions disseminating time spaceconclusionthough nonmhc susceptibility genes remain elusive ms present striking finding superimposed multiple sclerosis mother daughter vhld vhl gene known primary regulator nrf2 wellestablished target fdaapproved therapeutic dimethyl fumarate cases provide support studies determine whether vhld pathway related genes represent novel genetic link multiple sclerosis,1.0
experimental laboratory biomarkers multiple sclerosis conclusions interactions environmental genetic factors implicated development ms previous investigations identified wide range biomarkers can used diagnosis disease management molecules associated studies provide vital insight data help primary physicians improve clinical health outcomes ms patients,0.0
psychopharmacology patients multiple sclerosis greece period 20172019 multiple sclerosis ms highly comorbid mental disorders disease stage psychiatric manifestations may precede onset neurological symptoms well diagnosis neuropsychiatric comorbidities associated elevated risk ms disability progression therefore people multiple sclerosis pwms psychiatric comorbidities often experience significantly lower functional status perform worse objective neuropsychological assessment less,0.0
s1p analogues sew2871 baf312 fty720 affect human th17 treg generation ex vivo multiple sclerosis immunemediated neurodegenerative disease il23mediated signaling th17 cells play critical roles disease pathogenesis murine models disease humans sphingosine 1 phosphate s1p regulates migration several types immune cells including th17 cells s1p analogues fingolimod fty720 siponimod baf312 approved currently used ms treatment immunomodulatory roles fty720 defined however different s1p,0.0
breaking barriers remyelination multiple sclerosis chronically demyelinated axons rendered susceptible degeneration loss trophic support oligodendrocytes myelin process underlies disability progression multiple sclerosis promoting remyelination promising neuroprotective therapeutic strategy date achieved simply promoting oligodendrocyte precursor cell differentiation clear detailed understanding molecular mechanisms underlying failed,1.0
experiences receiving diagnosis multiple sclerosis metasynthesis qualitative studies conclusions synthesis highlights need providing personcentred support advice time diagnosis presents conceptual map adjustment designing interventions improve adjustment following ms diagnosisimplications rehabilitationthe period surrounding multiple sclerosis diagnosis can stressful psychologically demandingchallenges disruptions diagnosis can threaten sense self resulting negative emotionsadaptive coping skills support,0.0
correction use modified rio score determining treatment failure patients multiple sclerosis retrospective descriptive case series study abstract,0.0
serum glial fibrillary acidic protein body fluid biomarker valuable prognostic neurological disease systematic review astrocytes abundant cell type human central nervous system play important role regulation neuronal physiology neurological disorders astrocyte disintegration leads release glial fibrillary acidic protein gfap tissue bloodstream elevated serum levels gfap can serve blood biomarkers useful prognostic tool facilitate early diagnosis several neurological diseases ranging stroke neurodegenerative,0.0
combinational role vitamin d conditions multiple sclerosis patients abstract,0.0
molecular pharmacology novel potential therapeutic applications fingolimod fingolimod welltolerated highly effective diseasemodifying therapy successfully utilized management multiple sclerosis active metabolite fingolimodphosphate acts sphingosine1phosphate receptors s1prs bring array pharmacological effects initially recognized novel agent can profoundly reduce tcell numbers circulation cns thereby suppressing inflammation ms now rapidly increasing knowledge,0.0
problems consider determining regimen treatment juvenile systemic sclerosis treatment case report tocilizumab monotherapy succeeded efficiently safely juvenile systemic sclerosis ssc rare condition results various disorders including growth retardation learning disabilities addition impaired quality life due fibrosis microvascular disorders multiple organs recently efficacies immunosuppressants cyclophosphamide mycophenolate mofetil well biological agents reported adult patients ssc however consensus treatment juvenile ssc due,0.0
polygenic risk score association multiple sclerosis susceptibility phenotype europeans polygenic inheritance plays pivotal role driving multiple sclerosis susceptibility inflammatory demyelinating disease central nervous system developed polygenic risk scores prs multiple sclerosis assessed associations disease status severity cohorts european descent largest genomewide association dataset multiple sclerosis date n 41 505 leveraged generate prs scores serving informative susceptibility marker tested,1.0
quality life experience national multiple sclerosis society strategic plan priorities people multiple sclerosis findings path analysis conclusion findings revealed relationships among mental health demographic factors overall ms experiences qol nmss participation resonance mission nmss complex highly nuanced yet strongly correlated importantly study highlights strong influence variables readily amenable change programmatic clinical intervention active selfmanagement participation,0.0
nicotine inflammatory diseases antiinflammatory proinflammatory effects antiinflammatory alkaloid nicotine plays dual roles treating diseases reviewed antiinflammatory proinflammatory effects nicotine inflammatory diseases including inflammatory bowel disease arthritis multiple sclerosis sepsis endotoxemia myocarditis oral skin muscle inflammation etc mainly concerning administration methods different models therapeutic concentration duration relevant organs tissues according data analysis,0.0
neurodegeneration convergent factors contributing deterioration cytoskeleton alzheimers disease cerebral ischemia multiple sclerosis review cytoskeleton main intracellular structure determines morphology neurons maintains integrity therefore disruption structure function may underlie several neurodegenerative diseases review summarizes current literature tau protein microtubuleassociated protein 2 map2 neurofilaments common denominators pathological conditions alzheimers disease ad cerebral ischemia multiple sclerosis ms insights,0.0
chemokinedriven migration proinflammatory cd4sup+ sup t cells cns autoimmune disease proinflammatory cd4 + t helper th cells drive pathogenesis many autoimmune conditions recent advances modified views phenotype proinflammatory th cells autoimmunity extending breadth known th cell subsets operate drivers responses heterogeneity plasticity within th1 th17 cells discovery subsets th cells dedicated production proinflammatory cytokines gmcsf led advances,0.0
identify report systematic review background examine relationship vitamin b12 folate concentrations cognitive function fatigue measures physical function quality life patientcentred outcomes homocysteine plasma concentrations intermediate marker cobalamin folate deficiency patients multiple sclerosis ms methods systematic searches eligible articles medline cinahl embase scopus web science opengray databases conducted 1983 march 2021,0.0
microglia polarization m1 m2 neurodegenerative diseases microgliamediated neuroinflammation common feature neurodegenerative diseases alzheimers disease ad parkinsons disease pd amyotrophic lateral sclerosis als multiple sclerosis ms microglia can categorized two opposite types classical m1 alternative m2 though theres continuum different intermediate phenotypes m1 m2 microglia can transit one phenotype another m1 microglia release inflammatory mediators induce,0.0
circulating memory b cells early multiple sclerosis exhibit increased iga + cells globally decreased baffr expression ebvrelated igm + cell signature multiple sclerosis ms immunemediated inflammatory disease central nervous system results demyelination axons inefficient signal transmission reduced muscular mobility recent findings suggest b cells play significant role disease development pathology explore b cell profiles peripheral blood 28 treatmentnaive patients early ms assessed using flow cytometry compared 17 healthy controls conventional,1.0
genetically predicted coffee consumption amyotrophic lateral sclerosis objective observational studies indicated association coffee consumption amyotrophic lateral sclerosis als nevertheless whether association causal still unclear conducted mendelian randomization study explore whether coffee consumption causally related als methods two genomewide association studies gwass investigating coffee consumption n 129 422 375 833 respectively adopted define instrumental variables coffee,0.0
effect noninvasive spinal cord stimulation anorectal function individuals spinal cord injury case series spinal cord injury sci devastating condition impacts multiple organ systems neurogenic bowel dysfunction nbd frequently occurs sci leading reduced sensation bowel fullness bowel movement often leading constipation fecal incontinence spinal neuromodulation proven successful modality improve sensorimotor autonomic function patients spinal cord injuries pilot data presented represents first demonstration using,0.0
cuprizone intoxication results myelin vacuole formation myelin damage histopathological hallmark multiple sclerosis lesions results post mortem studies suggest impaired myelinaxon interaction characterized focal myelin detachments early event lesion genesis study investigated ultrastructural changes axonmyelin interface cuprizone model using serial block face scanning electron microscopy immunohistochemistry show noninflammatory injury oligodendrocytes cuprizone,1.0
factors associated requesting accommodations among people multiple sclerosis background almost one million individuals living multiple sclerosis ms united states majority diagnosed 20s early stages careers employees ms experience various jobrelated challenges high unemployment underemployment accommodations assist individuals ms obtain maintain employment yet current understanding factors affecting decisions request withhold accommodations limited objective study aimed explore barriers facilitators workplace accommodation requests among individuals ms qualitative approach methods eightysix participants recruited agencies serving individuals ms us content analysis conducted examine responses one openended question related individual mss perception barriers facilitative strategies request accommodations results ten overarching themes related barriers facilitators requesting accommodations identified among three facilitators ie positive work environment employer compliance flexibility employee selfadvocacy proactivity seven barriers ie employers lack knowledge americans disabilities act accommodations employers discrimination resistance accommodation requests employees fear anxiety request due associated stigma employees lack knowledge accommodations disability resources well inaccessible workspace conclusions rehabilitation professionals can educate empower employees ms disclose disability request needed accommodations rehabilitation professionals also can educate employers individuals ms obligations laws provide accommodations sensitize coworkers individuals ms regarding disability keywords barriers disability facilitators multiple sclerosis workplace,0.0
proteinlosing gastroenteropathy complicated asymptomatic primary biliary cholangitis refractory immunosuppressant improved helicobacter pylori eradication case report background proteinlosing gastroenteropathy plge syndrome chief complaint hypoalbuminemia occurs due plasma protein leakage gastrointestinal tract leading general edema ascites pleural effusionscase presentationa 71yearold woman visited another hospital evaluation hypoalbuminemia systemic edema hospitalized close inspection hypoalbuminemia diagnosed plge steroid azathioprine therapy prescribed however hypoalbuminemia improve patients condition worsened due anasarca hospitalization prolonged patient transferred hospital infected helicobacter pylori performed h pylori eradication following h pylori eradication edema improved remarkablyconclusionwe present first case wherein h pylori eradication successfully improved protein leakage lower gastrointestinal tract patient diagnosed plge complicated refractory immunosuppressant treatment h pylori eradication considered patients plge complicated h pylori infection without specific endoscopic finding refractory immunosuppressants,0.0
gene therapy yeast ndi1 mitochondrial complex dysfunction rotenoneinduced parkinsons disease models vitro vivo abstractpurposeparkinsons disease pd second common neurodegenerative disease without cure effective treatment study explores whether yeast internal nadhquinone oxidoreductase ndi1 can functionally replace defective mammalian mitochondrial complex may provide gene therapy strategy treating sporadic pd caused mitochondrial complex dysfunctionmethodrecombinant lentivirus expressing ndi1 transduced shsy5y cells recombinant adenoassociated virus type 5 expressing ndi1 transduced right substantia nigra pars compacta snpc mouse pd cell mouse models established rotenone treatment therapeutic effects ndi1 rotenoneinduced pd models vitro vivo assessed neurobehavior neuropathology mitochondrial functions using apomorphineinduced rotation test immunohistochemistry immunofluorescence western blot complex enzyme activity determination oxygen consumption detection atp content determination ros measurementresultsndi1 expressed localized mitochondria shsy5y cells ndi1 resisted rotenoneinduced changes cell morphology loss cell viability accumulation synuclein ps129 synuclein mitochondrial ros production mitochondriamediated apoptosis basal maximal oxygen consumption mitochondrial coupling efficiency basal oligomycinsensitive atp complex activity cell model significantly increased rotenone + ndi1 group compared rotenone + vector group ndi1 efficiently expressed dopaminergic neurons right snpc without obvious adverse effects rotation number right side ndi1treated side significantly increased compared left side untreated side mouse model number viable dopaminergic neurons expression tyrosine hydroxylase total maximal oxygen consumption mitochondrial coupling efficiency complex enzyme activity right substantia nigra content dopamine right striatum significantly increased rotenone + ndi1 group compared rotenone + vector groupconclusionyeast ndi1 can rescue defect oxidative phosphorylation rotenoneinduced pd cell mouse models ameliorate neurobehavioral neuropathological damages results may provide basis yeast ndi1 gene therapy sporadic pd caused mitochondrial complex dysfunction,0.0
transcriptomic characterization molecular mechanisms induced rgma skeletal muscle nuclei accretion hypertrophy background repulsive guidance molecule rgma gpianchor axon guidance molecule first found play important roles neuronal development rgma expression patterns signaling pathways via neogenin bmp coreceptors indicated axon guidance molecule also working processes diseases including myogenesis previous works research group consistently shown rgma expressed skeletal muscle cells overexpression induces nuclei accretion hypertrophy muscle cell lineages however cellular components molecular mechanisms induced rgma differentiation skeletal muscle cells poorly understood work global transcription expression profile rgmatreated c2c12 myoblasts differentiation stage obtained rnaseq reportedresultsrgma treatment modulate expression pattern 2 195 transcripts c2c12 skeletal muscle 943 upregulated 1 252 downregulated among rgma interfered expression several rna types including categories related regulation rna splicing degradation data also suggested nuclei accretion induced rgma due capacity induce expression transcripts related adherens junsctions extracellularcell adhesion rgma effects muscle hypertrophy might due activation mtorakt independent axis ii regulation expression transcripts related atrophy finally rgma induced expression transcripts encode skeletal muscle structural proteins especially sarcolemma also associated striated muscle cell differentiationconclusionsthese results provide comprehensive knowledge skeletal muscle transcript changes pathways response rgma,0.0
microbiota medicine towards clinical revolution abstractthe human gastrointestinal tract inhabited largest microbial community within human body consisting trillions microbes called gut microbiota normal flora site many physiological functions enhancing host immunity participating nutrient absorption protecting body pathogenic microorganisms numerous investigations showed bidirectional interplay gut microbiota many organs within human body intestines lungs brain skin large body evidence demonstrated decade ago gut microbial alteration key factor pathogenesis many local systemic disorders regard deep understanding mechanisms involved gut microbial symbiosis dysbiosis crucial clinical health field review recent studies involvement gut microbiota pathogenesis many diseases also elaborate different strategies used manipulate gut microbiota prevention treatment disorders future medicine strongly related quality microbiota targeting microbiota dysbiosis will huge challenge,0.0
mesenchymal stem cells natural killer cells interaction mechanisms potential clinical applications abstractnatural killer cells nk cells innate immune cells activated fight tumor cells virusinfected cells nk cells also play important role graft versus leukemia response however can overdevelop inflammatory reactions secreting inflammatory cytokines increasing th1 differentiation eventually leading tissue damage today researchers attributed autoimmune diseases gvhd nk cells hand shown mesenchymal stem cells mscs can modulate activity nk cells researchers shown nk cells can cause mscs lysis therefore considered necessary investigate effect two cells signaling pathway contact also clinical applications,0.0
connexin 43 gap junctionmediated astrocytic network reconstruction attenuates isofluraneinduced cognitive dysfunction mice background postoperative cognitive dysfunction pocd common complication following anesthesia surgery general anesthetic isoflurane potential neurotoxicity induces cognitive impairments exact mechanism remains unclear astrocytes form interconnected networks adult brain gap junctions gjs primarily comprise connexin 43 cx43 play important roles brain homeostasis functions memory however role gjcx43mediated astrocytic network isofluraneinduced cognitive dysfunction definedmethods4monthold male c57bl 6 mice exposure longterm isoflurane induce cognitive impairment simulate vitro isofluraneinduced cognitive dysfunctionlike condition primary mouse astrocytes subjected longterm isoflurane exposure cognitive function assessed ymaze fear conditioning tests western blot used determine expression levels different functional configurations cx43 morphology gjscx43 evaluated immunofluorescence staining levels il1 il6 examined elisa ability gjscx43mediated intercellular communication examined lucifer yellow dye transfer assay ethidium bromide uptake assays used measure activity cx43 hemichannels ultrastructural morphology astrocyte gap junctions tripartite synapse observed transmission electron microscopyresultsafter longterm isoflurane anesthesia gjs formed cx43 mouse hippocampus primary mouse astrocytes significantly reduced gjs function impaired hemichannel activity enhanced levels il1 il6 increased mice showed significant cognitive impairment treatment novel gjcx43 enhancer zp1609 gjcx43mediated astrocytic network function enhanced neuroinflammation alleviated ameliorated cognition dysfunction induced longterm isoflurane exposure however zp1609 enhances astrocytic network promoting cx43 form gjs without affecting hemichannel activity additionally data showed longterm isoflurane exposure alter structure tripartite synapseconclusionour results reveal novel mechanism gjcx43mediated astrocytic network involved isofluraneinduced neuroinflammation cognitive impairments provides new mechanistic insight pathogenesis pocd identifies potential targets treatment,0.0
patterns acceptance mindfulness values japanese patients type 2 diabetes mellitus webbased survey background acceptance commitment therapy act model human functioning uses behavioral processes acceptance mindfulness values together compose psychological flexibility ability contact present moment fully conscious human either change persist serves valued ends increase effectiveness interventions medical treatment diabetes important examine effects patients type 2 diabetes promoting active component patterns act study explores pointsmethodsquestionnaires administered type 2 diabetes patients registered database research service provider data collected analyzed total 211 patients mean age sd 5884 years old 1025 1469 females resultscluster analysis yielded four clusters average average levels acceptance mindfulness values flexibility high levels acceptance mindfulness values values low average levels acceptance mindfulness low level values values high average levels acceptance mindfulness high level values patients flexibility values high clusters significantly fewer depressive symptoms clusters however members values high cluster demonstrated significantly higher glycated hemoglobin levels clustersconclusionsthe results indicate part act model necessary managing diabetes treatment improving quality life importance values emphasized act diabetes patients argue given results acceptance mindfulness important japanese patients type 2 diabetes study limited japanese patients type 2 diabetes research subject population must expanded people areas different racial backgrounds,0.0
pancreatic neuroendocrine neoplasms updates genomic changes inherited tumour syndromes sporadic tumours based classification pancreatic neuroendocrine neoplasms pannens neuroendocrine neoplasms greatest rate increase incidence approximately 10 pannens arise inherited tumour syndromes include multiple endocrine neoplasia type 1 multiple endocrine neoplasia type 4 von hippellindau syndrome neurofibromatosis type1 tuberous sclerosis complex 1 2 cowden syndrome glucagon cell hyperplasia neoplasia well familial insulinomatosis sporadic pannens driver mutations,0.0
use evidenceinformed deliberative processes health insurance benefit package revision iran conclusion implementation priority setting process ms diagnosis treatment services likely improved legitimacy decisionmaking involving stakeholders engaged deliberation based available evidence stepwise transparent process expected improve quality care ms patients well financial accessibility zero net budget impact pilot project served help irans health system move faster toward uhc broader,0.0
effectiveness physical therapy interventions reducing falls among people multiple sclerosis systematic review metaanalysis conclusion overall low moderate quality evidence presented showed effectiveness pt interventions reduce fall outcomes pwms limited however homebased exercise showed potential reduce fall outcomes ambulatory pwms need develop pt interventions reduce fall outcomes nonambulatory pwms due scarcity evidence population,0.0
genetics diagnosis pediatric neurocutaneous disorders neurofibromatosis tuberous sclerosis complex neurofibromatosis nf tuberous sclerosis complex tsc two common neurocutaneous disorders transmitted autosomal dominant case nf also mosaic conditions causative genetic mutations neurocutaneous disorders can lead benign skin changes uninhibited growth proliferation multiple organ systems due loss tumor suppression mapk mtor signaling pathways common clinical features include nf include pigmented lesions,0.0
discovery synthesis evaluation novel reversible monoacylglycerol lipase radioligands bearing morpholine3one scaffold monoacylglycerol lipase magl serine hydrolase plays important role endocannabinoid degradation brain recently emerged promising therapeutic target treatment neuroinflammatory neurodegenerative diseases multiple sclerosis alzheimers disease parkinsons disease development maglspecific radioligands noninvasive imaging positronemission tomography pet deepen knowledge relevant pathological changes,0.0
growing ganja permission real gateway thailands promising industrial crop abstractthe current revision thailands narcotics act 2563 permits thai corporations produce cannabis ganja therapeutic purposes well conduct beneficial research development science agriculture ganja possession distribution use still illegal thailand law removes certain elements cannabis sativa including hemp narcotic lists december 2020 thailands narcotics board plans remove totally lists last quarter 2022 thai food drug administration thai fda board maintains exclusive licensing authority assess applications provide authorization due complexity registration process view analyzed guidelines obtaining cannabis production license apparent announced law inline regulations setout many countries terms security prevention misuse criteria however fall merely onto government gains rather public interests avoid claimed state monopoly several types licensing issued future depending genuine purpose farmers complete regulation process conditions obtaining ganja growing license thailand highlighted discussed review,0.0
genetically predicted telomere length multiple sclerosis abstractsbackground previous epidemiological studies indicated role telomere length multiple sclerosis ms severity phenotype however studies failed establish causality telomere length ms susceptibility hence performed twosample mendelian randomization mr analysis explore causal relationship telomere length ms susceptibilitymethods used data genetic variants associated leukocyte telomere length instrumental variables ivs identified largest latest genomewide association study gwas uk biobank ukb 472 174 participants summary data ms obtained international multiple sclerosis genetics consortium performed twosample mr analyses using inversevariance weighted method primary approach mr approaches including mregger inverse variance weighted multiplicative random effects weighted median simple median weighted modebased methods causal analysis using summary effect estimates cause also conducted detect result robustnessresults genetic liability longer telomere length associated higher risk ms susceptibility odds ratio per onesd telomere length 191 95 confidence interval ci 148247 p804107 results remained consistent across multiple sensitivity analysesconclusions study supports causal relationship longer telomere length increased risk ms susceptibility,0.0
transmembrane protein 119 neither specific reliable marker microglia glia 2022 mar 4 doi 101002 glia24164 online ahead printabstractmicroglia resident innate immune cells central nervous system cns parenchyma determine impact microglia disease development progression neurodegenerative neuroinflammatory diseases essential distinguish microglia peripheral macrophages monocytes eventually equally recruited suggested transmembrane protein 119 tmem119 serves reliable microglia marker discriminates resident microglia bloodderived macrophages human murine brain investigated validity tmem119 microglia marker four vivo models cuprizone intoxication experimental autoimmune encephalomyelitis eae permanent filament middle cerebral artery occlusion fmcao intracerebral 6hydroxydopamine 6ohda injections well post mortem multiple sclerosis ms brain tissues applied animal models post mortem ms tissues found increased densities ionized calciumbinding adapter molecule 1+ iba1+ cells paralleled significant decrease tmem119 expression addition cell types peripheral tissues ie follicular dendritic cells brown adipose tissue also found express tmem119 summary study demonstrates tmem119 exclusively expressed microglia label microglia especially cellular stress conditions since novel transgenic lines developed label microglia using tmem119 promotor downregulation tmem119 expression might interfere results thus considered working transgenic mouse modelspmid35246882 doi101002 glia24164,0.0
eculizumab versus rituximab generalised myasthenia gravis j neurol neurosurg psychiatry 2022 mar 4jnnp2021328665 doi 101136 jnnp2021328665 online ahead printabstractobjective myasthenia gravis mg common autoimmune disorder affecting neuromuscular junction however evidence shaping treatment decisions particularly treatmentrefractory cases sparse rituximab eculizumab may considered therapeutic options refractory mg insufficient symptom control standard immunosuppressive therapiesmethods retrospective observational study included 57 rituximabtreated 20 eculizumabtreated patients mg compare efficacy treatment agents generalised therapyrefractory antiacetylcholine receptor antibody antiachrab mediated mg observation period 24 months change quantitative myasthenia gravis qmg score defined primary outcome parameter differences groups determined optimal full propensity score matching modelresults groups comparable terms clinical demographic characteristics eculizumab associated better outcome compared rituximab measured change qmg score 12 24 months treatment minimal manifestation disease frequently achieved eculizumabtreated patients rituximabtreated patients 12 24 months baseline however risk myasthenic crisis mc ameliorated either groupinterpretation retrospective observational study provides first realworld evidence supporting use eculizumab treatment refractory antiachrab positive mg nonetheless risk mc remained high prompts need intensified monitoring research effort aimed vulnerable patient cohortpmid35246490 doi101136 jnnp2021328665,0.0
multimodal prognostic features seizure freedom epilepsy surgery j neurol neurosurg psychiatry 2022 mar 4jnnp2021327119 doi 101136 jnnp2021327119 online ahead printabstractobjective accurate preoperative predictions seizure freedom following surgery focal drug resistant epilepsy remain elusive objective systematically evaluate metaanalyses epilepsy surgery seizure freedom primary outcome identify clinical features consistently prognostic included future modelsmethods searched pubmed cochrane using freetext medical subject heading mesh terms according preferred reporting items systematic reviews metaanalyses study registered prospero classified features prognostic nonprognostic uncertain seven subcategories clinical imaging neurophysiology multimodal concordance genetic surgical technique pathology propose structural causal model based featuresresults found 46 features 38 metaanalyses 22 years following consistently prognostic across metaanalyses febrile convulsions hippocampal sclerosis focal abnormal mri singlephoton emission computed tomography spect coregistered mri focal ictal interictal eeg eegmri concordance temporal lobe resections complete excision histopathological lesions tumours focal cortical dysplasia type iib severe learning disability predictive poor prognosis others including sex side resection nonprognostic limited metaanalyses investigating genetic contributions structural connectivity multimodal concordance adjusted known confounders performed corrections multiple comparisonssignificance seizurefree outcomes improved decades epilepsy surgery despite multitude models none prognosticate accurately list multimodal populationinvariant prognostic features proposed structural causal model may serve objective foundation statistical adjustments plausible confounders use highdimensional modelsprospero registration number crd42021185232pmid35246493 doi101136 jnnp2021327119,0.0
evaluation polarity switching untargeted lipidomics using liquid chromatography coupled high resolution mass spectrometry untargeted lipidomics using liquid chromatography highresolution mass spectrometry lchrms performed using polarity switching positive negative polarity separately set serum samples performances methods evaluated polarity switching causes increase cycle time hrms measurements 118 s cycle vs 027 s cycle resulting fewer data points across chromatographic peaks coefficient variation cv average lower,0.0
surgery tuberous sclerosis complexrelated epilepsy risk factors unfavorable seizure outcome abstract purpose study aimed identify risk factors postoperative seizure outcome consecutive cohort patients operated tscrelated focal epilepsy evaluating several presurgical surgical variables including also mrivisible brain abnormalities cortical tubers methods retrospective study included 51 patients surgically treated drugresistant focal epilepsy histological diagnosis cortical tuber followed least 12 months postoperatively investigated association several potentially explanatory variables seizure outcome univariate multivariate analysis whole cohort subgroups patients single multiple tubers respectively results median postoperative followup 115 months iqr 63168 549 patients engels class final control whole cohort variables independently associated unfavorable seizure outcome engels classes iiiv preoperative nonfocal interictal eeg rr 5 ci 246639 presence subependymal nodules sen rr 353 ci 171456 seizure onset first year age rr 356 ci 091689 nonfocal interictal eeg independently associated unfavorable outcome also subgroup patients multiple tubers rr 434 ci 223537 presence sen p00221 extracentral nervous system lesions p 00152 predicted unfavorable seizure outcome patients single tuber conclusion surgery represents effective option seizure control patients tscrelated epilepsy identification preoperative risk factors seizure outcome helpful optimizing patients selection surgery presurgical counseling keywords epilepsy surgery risk factors seizure outcome subependymal nodules sen tuberous sclerosis complex tsc,0.0
7deacetylgedunin suppresses proliferation human rheumatoid arthritis synovial fibroblast activation nrf2 signaling rheumatoid arthritis ra chronic autoimmune disease characterized high incidence however effective therapies ra therefore urgent discover new drugs ra treatment nuclear factor erythroid 2 nfe2 related factor nrf2 can effectively protect arthritic inflammatory diseases diverse stages regulating redox balance detoxification metabolism inflammation dimethyl fumarate dmf targets nrf2 pathway approved,0.0
contemporary advances antibodymediated encephalitis antilgi1 anticaspr2 antibody ab mediated encephalitides encephalitides antibodies directed leucinerich gliomainactivated 1 lgi1 contactinassociated proteinlike 2 caspr2 represent two increasingly well characterised forms autoimmune encephalitis share overlapping distinct clinical features mediated autoantibodies directed differing proteins complexed voltagegated potassium channels unique genetic predisposition identified date herein summarise disease mechanisms clinical,0.0
qsmrimnet imbalanceaware learning identification chronic active multiple sclerosis lesions quantitative susceptibility maps abstract background purpose chronic active multiple sclerosis ms lesions characterized paramagnetic rim edge lesion associated increased disability patients quantitative susceptibility mapping qsm mri technique sensitive chronic active lesions termed rim + lesions qsm present qsmrimnet data imbalanceaware deep neural network fuses lesionlevel radiomic convolutional image features automated identification rim + lesions qsm methods qsm t2weightedfluidattenuated inversion recovery t2flair mri brain collected 3 t 172 ms patients rim + lesions manually annotated two human experts followed consensus third expert total 177 rim + 3986 rim negative rim lesions automated rim + detection algorithm qsmrimnet consists twobranch feature extraction network synthetic minority oversampling network classify rim + lesions first network branch image feature extraction qsm t2flair second network branch fully connected network qsm lesionlevel radiomic feature extraction oversampling network designed increase classification performance imbalanced data results lesionlevel fivefold cross validation framework proposed qsmrimnet detected rim + lesions partial area receiver operating characteristic curve proc auc 0760 clinically relevant false positive rates less 01 considered method attained area precision recall curve pr auc 0704 qsmrimnet outperformed stateoftheart methods applied qsm proc auc pr auc subjectlevel comparing predicted rim + lesion count human expert annotated count qsmrimnet achieved lowest mean square error 098 highest correlation 089 95 ci 086 092 conclusion study develops novel automated deep neural network rim + ms lesion identification using t2flair qsm images keywords chronic active lesions convolutional neural network multiple sclerosis quantitative susceptibility mapping radiomic features,0.0
physiotherapy management acute transverse myelitis pediatric patient nigerian hospital case report background transverse myelitis rare neurological disorder spinal cord caused inflammation damage myelin sheath neurons spinal cord across one spinal segments causes disruption passage nervous signals leading motor sensory autonomic dysfunction affects physical psychological health well functional status patient case report presents physiotherapy evaluation management acute transverse myelitis pediatric patientcase presentationa 17yearold nigerian male diagnosed acute transverse myelitis referred physiotherapy team expert management patient presented severe muscle spasms frequent jerking movements shocking sensations hypertonicity spasticity modified ashworth scale 1+ right 2 right muscle strength lower limbs oxford muscle grading 3 5 left 1 5 left impaired functional status functional independence measure 70 126 patient tolerated participated physiotherapy interventions cryotherapy soft tissue mobilization splinting exercises free active resistance functional exercises ward outpatient clinic well subsequent home programmes free active resistance functional exercises patient also received medical pharmacological interventions ward 23 days therapy patient improved clinical outcomes including muscle spasm hypertonicity spasticity modified ashworth scale 0 bilaterally sensation muscle strength oxford muscle grading 5 5 bilaterally patients overall functional status also improved functional independence measure 117 126 conclusionsphysiotherapy improved symptoms acute transverse myelitis patient randomized controlled trials required replicate findings,1.0
multifocal micronodular pneumocyte hyperplasia lacking typical clinical features tuberous sclerosis complex case report literature review background multifocal micronodular pneumocyte hyperplasia mmph rare pulmonary manifestation tuberous sclerosis complex tsc distinctive histological characteristics case reports mmph associated tsc usually history typical clinical features seizures mental retardation skin lesions tsc present peculiar asymptomatic mmph case lacked history typical clinical features tsccase presentationa 56yearold man referred hospital bilateral groundglass opacities ggos chest computed tomography ct lasting 8 months complaint discomfort lack clinical manifestations diagnosis mmph tsc confirmed lung biopsy histopathology gene sequencing nonsense mutations tsc1 gene considering relevant literature review prognosis patients mmph generally stable special treatment given followed patient three years discharge clinical manifestations imaging features patient stableconclusionto best knowledge first case mmph lacking typical clinical manifestations tsc confirmed histopathology combined gene sequencing mmph considered one differential diagnoses multiple ggos lung even findings tsc recognized,0.0
microbiota inneuroinflammationandsynaptic dysfunction focus alzheimers disease background implication gut microbiota control brain functions health disease novel currently emerging concept accumulating data suggest gut microbiota exert action least part modulating neuroinflammation given link neuroinflammatory changes neuronal activity plausible gut microbiota may affect neuronal functions indirectly impacting microglia key player neuroinflammation indeed increasing evidence suggests interplay microglia synaptic dysfunction may involve microbiota among factors addition indirect microgliadependent actions microbiota neuronal activity recently recognized microbiota also affect neuronal activity directly stimulation vagus nervemain messagesthe putative mechanisms indirect direct impact microbiota neuronal activity discussed focusing alzheimers disease one studied neurodegenerative disorders prime cause dementia worldwide specifically mechanisms microbiotamediated microglial alterations discussed context peripheral central inflammation crosstalk next highlight role microbiota regulation humoral mediators peripheral immunity impact vagus nerve stimulation finally address whether microbiota perturbations affect synaptic neurotransmission downstream cognitive dysfunctionconclusionsthere strong increasing evidence supporting role gut microbiome pathogenesis alzheimers disease including effects synaptic dysfunction neuroinflammation contribute cognitive decline putative early intervention strategies based microbiota modulation appear therapeutically promising alzheimers disease still require investigation,0.0
physical exercise improve deteriorate treatment multiple sclerosis mitoxantrone experimental autoimmune encephalomyelitis study rats background mitoxantrone proved efficacy treatment multiple sclerosis ms fact physical exercise slow progression disease improve performance still debatable issue hence aimed studying whether combining mitoxantrone exercise value management msmethodsthirtysix male rats divided sedentary exercised groups 14day habituation period rats subjected exercise training rotarod 30 min day experimental autoimmune encephalomyelitis eae induction thereafter 17 consecutive days day 13 induction eae groups exercised sedentary divided untreated mitoxantrone treated ones disease development evaluated motor performance eae score cerebrospinal fluid csf used biochemical analysis brain stem cerebellum examined histopathological immunohistochemicallyresultsexercise training alone add significant value studied parameters except reducing foxp3 immunoreactivity eae group caspase3 mitoxantrone treated group unexpectedly exercise worsened mitoxantrone effect eae score bcl2 bax mitoxantrone alone decreased eae demyelination inflammation scores foxp3 immunoreactivity interleukin6 increased remyelination marker bdnf without change tumor necrosis factor clearly interrupted apoptotic pathway brain stem worsened eae mediated changes antiapoptotic bcl2 proapoptotic marker bax csfconclusionsthe neuroprotective effect mitoxantrone related remyelination immunosuppressive antiinflammatory potentials exercise training show added value mitoxantrone contrast disrupts apoptotic pathway,1.0
role th17 cells pathogenesis treatment breast cancer abstractbreast cancer severe problem worldwide due increase mortality prevalence among women despite early diagnostic procedures well advanced therapies investigation required find new treatment targets various factors mechanisms inflammatory conditions can play crucial role cancer progression among th17 cells identified effective cd4+ t cells play essential role autoimmune diseases inflammation may associated antitumor responses addition th17 cells one main factors involved cancer especially breast cancer via inflammatory process tumor immunity exact mechanism th17 cells entirely understood seems dual function tumor development various studies reported cytokines secreted th17 cells close relation cancer stem cells tumor microenvironment therefore play critical role growth proliferation invasion tumor cells hand studies reported t cells suppress growth tumor cells induction immune responses patients breast cancer compared normal individuals various studies reported th17 population dramatically increases peripheral blood results cancer progression seems th17 cells creating inflammatory conditions secretion cytokines including il22 il17 tnf il21 il6 can significantly enhance breast cancer progression therefore identify mechanisms factors involved activation development th17 cells can provide essential role preventing breast cancer progression present review role th17 cells breast cancer progression therapeutic potential investigated,0.0
clinical radiological evaluation cage subsidence following oblique lumbar interbody fusion combined anterolateral fixation background cage subsidence cs previously reported one common complications following oblique lumbar interbody fusion olif aimed assess impacts cs surgical results following olif combined anterolateral fixation determine radiological characteristics well related risk factorsmethodstwo hundred fortytwo patients underwent olif l45 minimum 12 months followup reviewed patients divided three groups according extent disk height dh decrease followup cs dh decrease 2 mm mild cs 2 mm dh decrease 4 mm severe cs dh decrease 4 mm clinical radiological results compared groups evaluate radiological features clinical effects risk factors csresultscs identified 79 326 patients including 48 198 mild cs 31 118 severe cs cs mainly identified within 1 month postoperatively progress 3 months postoperatively noted caudal endplate 44 557 terms clinical results patients mild cs group significantly worse cs group patients severe cs group significantly worse mild cs group significant difference fusion rate cs 926 151 163 mild cs 833 40 48 groups however significant lower fusion rate observed severe cs group 645 20 31 compared cs group cs related risk factors included osteoporosis 5976 dh overdistraction 1175 flat disk space 3309 endplate injury 6135 conclusioncs following olif early postoperative complication higher magnitudes cs associated worse clinical improvements lower intervertebral fusion osteoporosis endplate injury significant risk factors cs additionally flat disk space dh overdistraction also correlated increased probability cs,0.0
activation akt#x2f mammalian target rapamycin signaling peripheral blood women premature ovarian insufficiency correlation fmr1 expression background protein kinase b akt mammalian target rapamycin mtor signaling pathway regulates early follicular activation follicular pool maintenance female germline cells fragile x mental retardation 1 fmr1 regulates folliculogenesis variably expressed patients premature ovary insufficiency fmr1 expression supposed linked akt mtor signaling ovarian response dependent manner demonstrated recent vitro vivo studies female germline vitro vivomethodswe evaluated changes expression akt mtor signaling pathway genes real time pcr peripheral blood 74 patients premature ovarian insufficiency 56 fertile controls correlated expression fmr1 expressionresultsexpression genes akt1 tsc2 mtor s6k significantly abundant patients poi controls akt1 tsc2 mtor gene expression affected fmr1cgg repeat number 5untranslated region fmr1 s6k expression levels however significantly upregulated patients poi fmr1 premutation independent premutation expression mtor s6k tsc2 significantly correlated fmr1 patients furthermore grouped according ovarian reserve effect remained significant mtor s6k higher significance note patients premature ovarian insufficiency controlsconclusionsin premature ovarian insufficiency patients activation akt mtor signaling pathway remarkable putatively pathognomonic additionally seems triggered fmr1 mtor s6k linkage mechanism relevant premutation carriers,0.0
epidemiology familial multiple sclerosis iran national registrybased study background admittedly little known epidemiological signatures familial multiple sclerosis fms different geographical regions iranobjectiveto determine epidemiology risk fms incidence several provinces iran different ethnic population including fars tehran isfahan persians mazandaran mazanis kermanshah kurds chaharmahal bakhtiari lors methodsthis crosssectional registrybased study performed nationwide ms registry iran nmsri data collected 2018 2021 system registers baseline characteristics clinical presentations symptoms diagnostic treatments regional national levelsresultsa total 9200 patients including 7003 761 female 2197 239 male participated 19 patients reported family history ms order highest lowest fms prevalence follows fars 265 chaharmahal bakhtiari 211 tehran 205 isfahan 203 mazandaran 180 kermanshah 125 fms cases 747 1308 cases female 253 442 cases male fms occurrence much common females males pvalue 0001 mean age onset 30 years among fms cases substantially higher probability relapsingremitting ms secondaryprogressive ms found among fms cases sporadic ms sms p_value 0001 significant difference expanded disability status scale edss scores fms sms majority fms cases observed among firstdegree relatives highest rate siblings significant association ms risk positive familial history maternal paternal aunt uncle p_value 0043 p_value 0019 respectively multiple sclerosis occurrence among offspring females higher males p_value 0027 conclusionsin summary findings imply noteworthy upward trend fms iran even global prevalence suggests unique atlas fms prevalence multiethnic population despite highest rate fms within persian lor ethnicities statistically significant difference observed among provinces,0.0
quantitative evaluation disease severity connective tissue diseaseassociated interstitial lung disease dualenergy computed tomography background highresolution computed tomography hrct recommended diagnosing monitoring connective tissue diseaseassociated interstitial lung disease ctdild quantitative computed tomography potential precisely assess radiological severity ctdild still studyobjectiveto investigate whether dualenergy computed tomography dect novel quantitative technique can used quantitative severity assessment ctdildmethodsthis cross sectional study recruited adult ctdild patients underwent dect scans ice study october 2019 november 2021 dect parameters including effective atomic number zeff lung lobe volume monochromatic ct number mctn lung lobe evaluated ctdild classified extensive ctdild limited ctdild staging algorithm using combined forced vital capacity fvc predicted total extent ild tei ct dyspnea cough life quality scored borg dyspnea score leicester cough questionnaire lcq shortform 36 health survey questionnaire sf36 respectivelyresultsthere total 147 patients dect scans enrolled higher zeff value 3104 vs 2256 p 0001 higher mctn 72287 hu vs 80220 hu p 0001 lower lung volume 230951cm3 vs 347521cm3 p 0001 found extensive ctdild compared limited ctdild dect parameters significant moderate correlations fvcpredicted r 05420667 p 001 dlcopredicted r 03710427 p 001 tei r 04850742 p 001 receiver operating characteristic roc analysis indicated mctn averaged whole lung best performance extensive ctdild discrimination auc 0901 cutoff 76230 hu p 0001 sensitivity 821 specificity 854 zeff value independent risk factor dyspnea 3644 95 ci 18467192 p 0001 cough 3101 95 ci 15286294 p 0002 lung volume significantly contributed mental component summary mcs sf36 standardized 0198 p 005 conclusionsdect can applied evaluate severity ctdild,0.0
alzheimers disease journey healthy brain organ failure abstractas common dementia alzheimers disease ad exacts immense personal societal economic toll ad first described neuropathological level early 1900s today mechanistic insight select aspects ad pathogenesis ability clinically detect diagnose ad underlying ad pathologies living patients insights demonstrate ad complex insidious degenerative proteinopathy triggered aggregate formation time pathology drives neurofibrillary tangle nft pathology dysfunction virtually cell types brain ultimately overt neurodegeneration yet large gaps knowledge ad pathophysiology huge unmet medical need remain though largely conceptualize ad disease aging heritable nonheritable factors impact brain physiology either continuously specific time points lifespan thereby alter risk devolvement ad herein describe lifelong journey healthy brain birth death ad acknowledging many knowledge gaps remain regarding understanding ad pathogenesis ensure current lexicon surrounding ad changes inevitable incurable poorly manageable lexicon preventable curable manageable must address knowledge gaps develop therapies bigger impact clinical symptoms progression disease use interventions appropriate stage disease,0.0
physicians knowledge specific rare diseases associated factors national crosssectional study china background rare disease patients often experience diagnosis delays misdiagnosis may due lack knowledge rare diseases among physiciansobjectiveto assess chinese physicians knowledge specific rare diseases identify associated factorsmethodsthirtyfour patient organizations unique disease interest invited develop 3 knowledge questions rare disease assess physicians knowledge disease felt experienced total knowledge score participant ranged score 0 3 national crosssectional study conducted cohort 3197 physicians 6 provinces across western central eastern china demographic information participants collected including gender age birthplace income education hospital class working title working years specialty multiple linear regression analysis performed assess independent associations physician variables total knowledge scoreresultstwo thousand one hundred fifteen 6616 involved physicians obtained total knowledge score 2 3 median knowledge scores 10 294 rare diseases score 15 physicians female gender 008 p 005 females vs males monthly income 500010 000 rmb 011 p 001 500010 000 vs 5000 10 00030 000 rmb 014 p 005 associated higher score specialties physicians received relatively higher score included internal medicine obstetrics gynecology radiology intensive care unit surgeryconclusionsalmost two thirds participants average good level knowledge specific rare disease felt experienced physicians female gender monthly income 500010 000 rmb 10 00030000 rmb specialties internal medicine obstetrics gynecology radiology intensive care unit surgery associated relatively higher knowledge score,0.0
diagnosing transition secondary progressive multiple sclerosis spms stepbystep approach clinicians abstractupon approval diseasemodifying therapies dmts patients active secondary progressive phase multiple sclerosis spms became emerging need prospectively predict diagnose patients transitioning relapsingremitting secondary progressive phase ms whilst several research articles handle challenges diagnosing stage disease clear stepbystep diagnostic approach remains elusive review aims providing stepbystep diagnostic approach patients within transitioningnull ms based currently available research findings summarize gaps diagnostic approach recommendations future research area practice,0.0
cellular mechanisms underlying response resistance cdk4#x2f 6 inhibitors treatment hormone receptorpositive breast cancer abstractpharmacological inhibitors cyclindependent kinases 4 6 cdk4 6 now established standard care patients advanced hormone receptorpositive breast cancer canonical mechanism underlying cdk4 6 inhibitor activity suppression phosphorylation retinoblastoma tumor suppressor protein serves prevent cancer cell proliferation recent data suggest agents induce diverse effects within tumor stromal compartments serve explain aspects clinical activity review phenomena discuss might leveraged development novel cdk4 6 inhibitorcontaining combination treatments also briefly review various known mechanisms acquired resistance clinical setting,0.0
drug delivery strategy hepatocellular carcinoma therapy abstracthepatocellular carcinoma hcc one common malignant tumors worldwide high rates recurrence death surgical resection ablation therapy limited efficacy patients advanced hcc poor liver function pharmacotherapy firstline option patients traditional antitumor drugs disadvantages poor biological distribution pharmacokinetics poor target selectivity high resistance high toxicity nontargeted tissues recently development nanotechnology significantly improved drug delivery tumor sites changing physical biological characteristics drugs nanocarriers improve pharmacokinetics biological distribution selectively accumulate cytotoxic agents tumor sites systematically review tumor microenvironment hcc recent application nanotechnology hcc video abstract,0.0
persistently reduced humoral sustained cellular immune response first third sarscov2 mrna vaccination anticd20treated multiple sclerosis patients abstractobjective examine humoral cellular response multiple sclerosis patients anticd20 therapy third bnt162b2 mrna sarscov2 vaccinationmethodsa prospective longitudinal study design first throughout third vaccination danish american ms centers participants treated ocrelizumab antibody ab levels assessed third vaccination using sarscov2 igg ii quant assay abbott laboratories b tlymphocytes enumeration done bd multitest6color tbnk reagent spikespecific tcell responses measured pbmc stimulation spike peptide pools jpt peptide technologies results found 140 377 333 seropositive first second third vaccinationthe median ablevels 742 bau ml range 852427 second vaccination well 437 bau ml range 783661 313 bau ml range 795070 third vaccination respectivelyno difference found levels second third vaccination p01475 seropositivity dropped 250 participants third vaccination relative reduction 333 p00020 difference found frequencies spike reactive cd4+ cd8+ tcells second 065 008 095 020 respectively third vaccination 099 022 13 034 respectivelyconclusion longitudinal cohort found significant increased humoral cellular response administration third sarscov2 mrna vaccination findings suggest need clinical strategies include allowance b cell reconstitution repeat vaccination provision preexposure prophylactic monoclonal antibodies,0.0
effects transcranial direct current stimulation patients poststroke fatigue study protocol doubleblind randomized controlled trial abstractintroductionpoststroke fatigue psf abnormal persistent unexplained physical psychological tiredness patients stroke common symptom stroke patients poor quality life bleak prognosis incidence rate 39 72 widely reported medicine treatments achieved lot progress still needs develop powerful new strategies powerful effect transcranial directcurrent stimulation tdcs shows great potential treatment psf study proposes apply doubleblind randomized controlled clinical trial explore effect safety tdcs combined routine rehabilitation psfmethods analysisone hundred patients psf will randomly divided two groups one groups will receive conventional rehabilitation therapy active tdcs whereas another group will receive conventional rehabilitation treatment sham tdcs groups will receive intervention 4 weeks time will undergo either active sham tdcs 20 min day 6 days week primary outcome fatigue severity scale fss will measured baseline every weekend intervention period secondary results fatigue impact scale fis functional assessment chronic illness therapy fatigue facitf specialized quality life scale stroke ssqol will measured baseline end intervention time 4 weeks throughout study adverse events adverse reactions will measured every treatment research study effects transcranial direct current stimulation patients poststroke fatigue approved ethics committee first affiliated hospital nanchang university clinical medicine ethics review 2015 043 nov 2015discussionthis study will provide insight efficacy transcranial directcurrent stimulation poststroke fatigue doubleblind randomized controlled trial whose aim assess effects tdcs psf study can provide information treatment psf study period followup allows greater accuracy singlecenter trial may limitation limitation study relatively small number participants thus influence chance experimental results completely ruled outtrial registrationchinese clinical trial registry chictr2000031120 registered march 22 2020 protocol version number v11,0.0
multilesion radiomics model discrimination relapsingremitting multiple sclerosis neuropsychiatric systemic lupus erythematosus eur radiol 2022 mar 3 doi 101007 s00330022086532 online ahead printabstractobjectives develop mribased multilesion radiomics model discrimination relapsingremitting multiple sclerosis rrms mimicker neuropsychiatric systemic lupus erythematosus npsle methods total 112 patients rrms n 63 npsle n 49 assigned training test sets ratio 31 lesions across whole brain manually segmented t2weighted fluidattenuated inversion recovery images single lesion 371 radiomics features extracted trained using machine learning algorithms producing radiomics index lesion ril lesion singlelesion radiomics model subject single lesions assigned one two disease courts based distance decision threshold radiomics index subject ris calculated mean ril value lesions higherweighted court accordingly subjectlevel discrimination model constructed compared performances two radiologistsresults subjectbased discrimination model satisfactorily differentiated rrms npsle training auc 0967 accuracy 0892 sensitivity 0917 specificity 0872 test sets auc 0962 accuracy 0931 sensitivity 1000 specificity 0875 significantly better singlelesion radiomics method training p 0001 test p 0001 besides discrimination model significantly outperformed senior radiologist training set training p 0018 test p 0077 junior radiologist training test sets training p 0008 test p 0023 conclusions multilesion radiomics model effectively discriminate rrms npsle providing supplementary tool accurate differential diagnosis two diseaseskey points radiomic features brain lesions rrms npsle different multilesion radiomics model constructed using merging strategy comprehensively superior singlelesionbased model discrimination rrms npsle rrmsnpsle discrimination model showed significantly better performance trend toward significance radiologistspmid35243524 doi101007 s00330022086532,0.0
carotid intimamedia thickness measurements patients multiple sclerosis ann med surg lond 2022 feb 9 75103348 doi 101016 jamsu2022103348 ecollection 2022 marabstractobjectives goal study evaluate mean carotid intimamedia thickness cimt patients multiple sclerosis ms methods crosssectional study 100 patients ms enrolled carotid intimamedia thickness measured doppler ultrasonography mean cimt compared different groups sex age body mass index bmi medications site ms plaques brain cervical mri addition disease duration annual relapse rate expanded disability status scale edss compared high normal cimt groupsresults among 100 patients sixtytwo percent patients female mean age 3595 932 years mean cimt 038 02 mm 22 patients abnormal cimt measures cimt significantly associated higher age p 001 prolonged disease duration p 0001 cimt associated disease factors types diseasemodifying drug p 005 conclusion multiple sclerosis might associated carotid atherosclerotic vascular diseasepmid35242318 pmcpmc8866135 doi101016 jamsu2022103348,0.0
cooccurrence fatigue depression people multiple sclerosis minireview front neurol 2022 feb 15 12817256 doi 103389 fneur2021817256 ecollection 2021abstractfatigue depression common conditions diagnosed people multiple sclerosis ms fatigue defined subjective lack physical mental energy present 3597 people ms classify one serious symptoms interfering daily activities influencing quality life depression diagnosed 50 people ms since fatigue depression frequently coexists may quite hard differentiate primary fatigue primary depression ms caused inflammatory oxidative nitrosative neurodegenerative processes leading demyelination axonal damage brain atrophy people ms comorbid fatigue depression reported increased serum cerebrospinal fluid concentration inflammatory mediators tumor necrosis factor interleukins il1a il1b il6 interferon neopterin moreover brain atrophy prefrontal frontal parietotemporal regions thalamus basal ganglia observed people ms fatigue depression secondary fatigue secondary depression people ms may caused emotional factors sleep disorders pain coexistence diseases use medications studies use diseasemodifying therapies positively influenced fatigue probably reducing inflammatory response proves fatigue depression closely related immunological factors minireview pathogenesis methods evaluation differentiation possible therapies fatigue depression ms discussedpmid35242093 pmcpmc8886154 doi103389 fneur2021817256,1.0
cannabinoids orthopedic setting literature review orthopedics 2022 mar 417 doi 103928 014774472022022511 online ahead printabstractpublic interest analgesic potential cannabinoids grown consensus regarding orthopedic applications available evidence identified cannabinoid use arthritis neuropathic pain fibromyalgia multiple sclerosis postoperative pain extracted information included risks preoperative use associations opioid dependence surgical complications limited evidence therapeutic benefit cannabinoids rheumatoid arthritis fibromyalgia cannabinoids indicated postoperative pain preoperative unregulated use linked postoperative opioid dependence cannabinoids may considered second thirdline treatment analgesia orthopedic pathologies orthopedics 202x xx x xxxx pmid35245146 doi103928 014774472022022511,0.0
magnims recommendations harmonization mri data ms multicenter studies neuroimage clin 2022 feb 25 34102972 doi 101016 jnicl2022102972 online ahead printabstractthere increasing need sharing harmonized data large cooperative studies essential develop new diagnostic prognostic biomarkers field multiple sclerosis ms issue become paramount importance due need translate clinical setting recent mri achievements however differences mri acquisition parameters image analysis data storage across sites potential bias represent substantial constraint review focuses state art recent technical advances desirable future developments harmonization acquisition analysis storage largescale multicentre mri data ms cohorts huge efforts currently made achieve requirements needed provide harmonized mri datasets ms field proper management large imaging datasets one greatest opportunities challenges coming years recommendations based achievements will provided despite advances made complexity tasks requires research specialized academical centres dedicated technical human resources collective efforts involving different professional figures crucial importance offer ms patients personalised management minimizing consumption resourcespmid35245791 doi101016 jnicl2022102972,0.0
sphingosine1phosphate receptor modulators versus interferon beta treatment relapsingremitting multiple sclerosis findings randomized controlled trials neurol sci 2022 mar 3 doi 101007 s1007202205988y online ahead printabstractbackground one kind diseasemodifying therapies sphingosine1phosphate receptor s1pr modulators fingolimod ozanimod siponimod approved developed treat multiple sclerosis ms several randomized controlled trials rct implemented compare efficacy safety s1pr modulators versus interferon beta treatment people relapsingremitting multiple sclerosis rrms method searched rcts implemented january 2010 june 2020 searching pubmed embase cochrane library databases central register controlled trials finally five rcts included study carefully choosingresult pooled 4304 patients 5 rcts primary outcome annualized relapse rate found annualized relapse rate s1pr modulator group 20 less interferon beta group 95ci 032 007 p 0002 s1pr modulators led significant reduction number new enlarging t2 lesions per scan number gadoliniumenhancing lesions compared interferon beta moreover s1pr modulators can also improve 54item multiple sclerosis quality life msqol54 physical health composite score p 00005 conclusion s1pr modulators exhibited good efficacy safety treatment rrms compared interferon beta according followup trials s1pr modulators can improve msqol54 physical health composite score may beneficial neurological recovery need research confirmpmid35243548 doi101007 s1007202205988y,0.0
ceramide kinase knockout ameliorates multiple sclerosislike behaviors demyelination cuprizonetreated mice life sci 2022 mar 1120446 doi 101016 jlfs2022120446 online ahead printabstractchanges sphingolipid metabolism regulate alter many cellular functions brain ceramide central molecule sphingolipid metabolism phosphorylated ceramide1phosphate c1p ceramide kinase cerk cerk c1p reported regulate many cellular responses roles immunerelated diseases vivo well elucidated thus investigated effects cerk knockout onset progression multiple sclerosis ms chronic neurodegenerative disease accompanied loss myelin sheaths brain msmodel mice prepared using diet containing copper chelator cuprizone cpz treatment 8weekold mice 02 cpz 8 weeks resulted motor dysfunction based rotarod test caused loss myelinrelated proteins mrps brain demyelination corpus callosum without affecting synaptophysin levels cerk knockout affect developmental changes mrps ameliorated motor dysfunction loss mrps demyelination brain cpztreated mice loss tail tonus another marker motor dysfunction detected 1 week without demyelination cpz treatment cerk knockoutindependent manner cpzinduced loss tail tonus progressed specifically female mice 68 weeks loss ameliorated cerk knockout activities ceramide metabolic enzymes including cerk lysates brain affected cpz treatment inhibition cerk candidate ms treatment discussedpmid35245521 doi101016 jlfs2022120446,1.0
role autoantibody testing modern personalized medicine clin rev allergy immunol 2022 mar 4 doi 101007 s12016021089186 online ahead printabstractpersonalized medicine pm aims individualized approach prevention diagnosis treatment precision medicine applies paradigm pm defining groups individuals akin characteristics often two terms used interchangeably quest pm advancing centuries traditional nosology classification defines groups clinical conditions relatively similar prognoses treatment options however individual characterized unique set multiple characteristics therefore achievement pm implies determination myriad demographic epidemiological clinical laboratory imaging parameters accelerated identification numerous biological variables associated diverse health conditions contributes fulfillment one prerequisites pm advent multiplex analytical platforms contributes determination thousands biological parameters using minute amounts serum biological matrixes finally big data analysis machine learning contribute processing integration multiplexed data individual level allowing personalized definition susceptibility diagnosis prognosis prevention treatment autoantibodies traditional biomarkers autoimmune diseases can contribute pm many aspects including identification individuals risk early diagnosis disease subphenotyping definition prognosis treatment well monitoring disease activity herein address autoantibodies can promote pm autoimmune diseases using examples systemic lupus erythematosus antiphospholipid syndrome rheumatoid arthritis sjgren syndrome systemic sclerosis idiopathic inflammatory myopathies autoimmune hepatitis primary biliary cholangitis autoimmune neurologic diseasespmid35244870 doi101007 s12016021089186,0.0
plasma neurofilament light glial fibrillary acidic protein lysosphingolipid biomarkers pharmacodynamics disease monitoring gm2 gm1 gangliosidoses patients mol genet metab rep 2022 feb 1 30100843 doi 101016 jymgmr2022100843 ecollection 2022 marabstractgm2 gm1 gangliosidoses genetic neurodegenerative lysosomal sphingolipid storage disorders earlier age onset severe clinical presentation progression infantile juvenile lateonset presentations broadly delineated separate phenotypic subtypes gene substrate reduction therapies act directly sphingolipidosis entering clinical trials treatment disorders simple use biomarkers disease monitoring urgently required support expedite clinical trials lysosphingolipid protein biomarkers sphingolipidosis neuropathology respectively assessed plasma samples 33 gm2 gangliosidosis patients 13 gm1 gangliosidosis patients compared 66 controls lysogm2 lysogm1 detectable 31 33 gm2 gangliosidosis 12 13 gm1 gangliosidosis patient samples respectively controls levels axonal damage marker neurofilament light nfl highly elevated gm2 gm1 gangliosidosis patient plasma samples overlap controls levels astrocytosis biomarker glial fibrillary acidic protein gfap also elevated samples patient populations albeit overlap controls gm2 gangliosidosis patient plasma nfl tau gfap lysogm2 highly elevated infantile onset patients indicating relationship severity phenotype plasma nfl liver lysogm2 also elevated gm2 gangliosidosis mouse model lowered treatment drug slowed disease progression results indicate lysosphingolipids nfl gfap potential monitor pharmacodynamics pathogenic processes respectively gm2 gm1 gangliosidoses patientspmid35242574 pmcpmc8856936 doi101016 jymgmr2022100843,0.0
longterm effect permanent demyelination axonal survival multiple sclerosis neurol neuroimmunol neuroinflamm 2022 mar 3 9 3 e1155 doi 101212 nxi0000000000001155 print 2022 mayabstractbackground objectives investigate longterm effect permanent demyelination axonal attrition examining association intereye asymmetry multifocal visual evoked potential mfvep latency delay subsequent thinning retinal ganglion cell axons patients longstanding history unilateral optic neuritis methods patients significant degree chronic demyelination intereye latency asymmetry 5 ms included study level optic nerve demyelination estimated baseline latency delay mfvep degree axonal loss assessed thinning retinal nerve fiber layer rnfl thickness baseline followup visits lowcontrast visual acuity lcva also evaluated baseline followup patients examined twice average interval 61 14 yearsresults 85 examined patients multiple sclerosis 28 satisfied inclusion criteria latency mfvep delayed rnfl thickness reduced eyes compared fellow eyes visits significant correlation latency asymmetry baseline followup intereye rnfl thickness asymmetry intereye asymmetry lcva baseline correlated baseline latency asymmetry mfvep baseline asymmetry rnfl thickness latency mfvep eyes improved slightly followup period whereas latency fellow eye remained stable contrast rnfl thickness significantly declined fellow eyes followup period rate rnfl thinning eyes however 2 times faster compared fellow eyes p 0001 furthermore baseline latency asymmetry significantly correlated rate rnfl thinning eyes followup p 0001 explaining almost half variability temporal rnfl progression millisecond latency delay ie 05 mm demyelination along optic nerve temporal rnfl thickness annually reduced 005discussion study provides clear vivo evidence chronic demyelination significantly accelerates axonal loss however process slow effect mild longterm monitoring required establish confidently measure neurodegenerative consequences demyelinationpmid35241572 doi101212 nxi0000000000001155,1.0
mechanistic target rapamycin regulator metabolic function oligodendroglia remyelination curr opin pharmacol 2022 mar 1 63102193 doi 101016 jcoph2022102193 online ahead printabstractdespite evidence prominent metabolic dysfunction within multiple sclerosis ms lesions mechanisms controlling metabolic shifts oligodendroglia poorly understood cuprizone model demyelination remyelination valuable tool assessing metabolic insult oligodendrocyte death myelin degradation closely resembling distal oligodendrogliopathy seen pattern iii ms lesions review discuss metabolic processes oligodendrocytes disrupted ms cuprizone model well evidence mechanistic target rapamycin mtor signaling key regulator oligodendroglial metabolic function efficient remyelinationpmid35245799 doi101016 jcoph2022102193,1.0
neurofilament light chain levels multiple sclerosis correlate lesions containing foamy macrophages acute axonal damage neurol neuroimmunol neuroinflamm 2022 mar 3 9 3 e1154 doi 101212 nxi0000000000001154 print 2022 mayabstractbackground objectives investigate whether white matter lesion activity acute axonal damage axonal density ms associate csf neurofilament light chain nfl levelsmethods 101 brain donors ms n 92 progressive ms n 9 relapsingremitting ms ventricular csf collected nfl levels measured white matter lesions classified active mixed inactive remyelinated microglia macrophage morphology active mixed lesions classified ramified ameboid foamy addition axonal density acute axonal damage assessed using bielschowsky amyloid precursor protein app immune histochemistryresults csf nfl measurements donors recent 1 year clinically silent stroke excluded csf nfl levels correlated negatively disease duration p 69e3 r 031 donors without atrophy csf nfl levels correlated positively proportion active mixed lesions containing foamy microglia macrophages p 985e10 p 175e3 respectively containing ramified microglia csf nfl correlated negatively proportions inactive p 566e3 remyelinated lesions p 003 normal appearing pyramid tract axonal density negatively correlated csf nfl levels bielschowsky p 002 r 031 presence acute axonal damage lesions related higher nfl levels app p 117e6 amount acute axonal damage higher active lesions foamy microglia macrophages rim mixed lesions foamy microglia macrophages compared active lesions containing ramified microglia macrophages p 46e3 p 002 respectively center border mixed lesions containing ramified microglia macrophages center p 46e3 border p 46e3 ns p 46e3 respectively center mixed lesions containing foamy microglia macrophages p 46e3 p 002 respectively inactive lesions p 46e3 p 46e3 respectively remyelinated lesions p 003 p 004 respectively discussion results demonstrated active mixed white matter ms lesions foamy microglia show high acute axonal damage correlate elevated csf nfl levels data support use biomarker monitor inflammatory demyelinating lesion activity axonal damage mspmid35241571 doi101212 nxi0000000000001154,1.0
dihydroquercetin ameliorates lpsinduced neuroinflammation memory deficit curr res pharmacol drug discov 2022 feb 10 3100091 doi 101016 jcrphar2022100091 ecollection 2022abstractdihydroquercetin dhq pentahydroxyflavanone used important suppliment oxidative stress related inflammation neuroinflammation neuroinflammation activation defense mechanism central nervous system upon exposure stimuli like amyloid lewy bodies lipopolysaccharide lps reactive oxygen species important pathophysiological mediator number neurodegenerative disorders including alzheimers disease parkinsons disease multiple sclerosis others objective present study evaluate neuroprotective effect dhq potent antioxidant molecule lps induced neuroinflammation first day experiment day1 neuroinflammation induced intracerebroventricular injection lps 5 g 5 l lateral ventricle rats dhq05 1 2 g kg injected tail vein respective groups day2 day10 behavioral studies showed dhq attenuated lpsinduced loss longterm memory working memory evaluated elevated plus maze ymaze test respectively biochemical estimations revealed dhq dosedependently attenuated lpsinduced decrease acetylcholine level increased acetylcholineesterase activity hippocampal region dhq also increased catalase activity decreased nitric oxide lipid peroxidation altered lps injection dhq also attenuated interleukin6 brain elevated upon lps induction decrease il6 attributed antioxidant activity hence dhq potential therapeutic candidate management neuroinflammation related neurodegenerative disorderspmid35243333 pmcpmc8857648 doi101016 jcrphar2022100091,1.0
twin study probes nonheritable immune aspects multiple sclerosis nat rev neurol 2022 mar 3 doi 101038 s4158202200641w online ahead printno abstractpmid35241814 doi101038 s4158202200641w,0.0
amniotic suspension allograft improves pain function rat meniscal tearinduced osteoarthritis model background osteoarthritis degenerative disease knee affects 250 million people worldwide due rising incidence knee replacement revision surgery need nonsurgical treatment reduce pain improve function patients knee osteoarthritis placentalderived allografts amniotic suspension allograft asa provide growth factors cytokines potentially modulate inflammatory environment osteoarthritis purpose study evaluate efficacy asa rat medial meniscal tear mmt induced osteoarthritis model histology microct synovial fluid biomarkers behavioral testingmethodsrats underwent mmt surgery day 7 day 0 rats injected either asa vehicle control fibroblast growth factor18 fgf18 behavioral testing including gait analysis pain threshold incapacitance knee swelling evaluated inlife along histology microct analysis cartilage synovial fluid testing postsacrifice one mmt cohort sacrificed day 10 day 21 third cohort acted safety arm receive mmt surgery rats injected either vehicle control asa evaluated day 3 day 21resultsbehavioral testing showed significant improvement pain threshold incapacitance gait following injection asa microct showed significant improvements cartilage thickness attenuation day 10 histology showed detrimental effects compared vehicle control day 21 synovial fluid analysis showed significant increase antiinflammatory il10 safety cohort showed significant differences except increase synovitis day 21 evidence xenogeneic response modelconclusionsin study injection asa well tolerated adverse events improvements pain function along cartilage properties day 10 observed increases antiinflammatory cytokines also seen along significant cartilage degeneration day 21 compared vehicle control study provides evidence use asa nonsurgical treatment knee oa,0.0
ceftriaxone prevent pneumonia inflammation cardiac arrest protect study protocol randomized placebocontrolled trial background pneumonia common infection outofhospital cardiac arrest ohca occurring 65 patients remain comatose return spontaneous circulation preventing infection ohca may 1 reduce exposure broadspectrum antibiotics 2 prevent hemodynamic derangements due local systemic inflammation 3 prevent infectionassociated morbidity mortalitymethodsthe ceftriaxone prevent pneumonia inflammation cardiac arrest protect trial randomized placebocontrolled singlecenter quadrupleblind patient treatment team research team outcome assessors noncommercial superiority trial conducted maine medical center portland maine usa ceftriaxone 2 g intravenously every 12 h 3 days will compared matching placebo primary efficacy outcome incidence earlyonset pneumonia occurring 4 days mechanical ventilation initiation concurrently t cellmediated inflammation bacterial resistomes will examined safety outcomes include incidence typeone immediatetype hypersensitivity reactions gallbladder injury clostridioides difficileassociated diarrhea trial will enroll 120 subjects approximately 3 4 yearsdiscussionthe protect trial novel 1 inclusion ohca survivors regardless initial heart rhythm 2 use lowrisk antibiotic available usa previously tested ohca 3 inclusion antiinflammatory effects ceftriaxone novel mechanism improved clinical outcomes 4 complete metagenomic assessment bacterial resistomes pre postceftriaxone prophylaxis longterm goal develop definitive phase iii trial powered mortality functional outcometrial registrationclinicaltrialsgov nct04999592 registered august 10 2021,0.0
sixmonth humoral response mrna sarscov2 vaccination patients multiple sclerosis treated ocrelizumab fingolimod abstractintroduction realworld clinical data suggest attenuated shortterm humoral response sarscov2 vaccines patients multiple sclerosis pwms receiving high efficacy disease modifying therapies dmts ocrelizumab ocr fingolimod fng longterm humoral response pwms treated hedmts poorly investigated aim study explore humoral response six months full cycle bnt162b2 mrna covid19 vaccine pwms treated ocr fng compare age sexmatched healthy controls hcs ii relationship humoral response clinical immunological characteristics studied populationmethods serum samples collected hcs pwms treated ocr fng following time points bnt162b2 mrna covid19 vaccine t0 4 t1 8 t2 16 t3 24 t4 weeks first dosesera stored 20c tested quantitative detection igg antibodies sarscov2 trimeric spike protein antitsp igg expressed binding antibody units bau t1 neutralizing antibodies nabs titres assessed relationship antitsp igg timepoints clinical laboratoristic analyses analysed spearman correlation coefficientresults 47 hcs 50 pwms 28 ocr 22 fng included study hcs mounted positive humoral response t1 preserved six months t1 571 pwms ocr p0001 compared hcs 409 fng p0001 positive humoral response t1 393 273 maintaining positive response sixth months t4 respectively strong positive correlation observed nabs titres antitsp igg t1 rho 087 p00001 nabs titres significantly higher hcs compared pwms ocr fng p00001 also found strong positive correlation timewindow since last ocr infusion antitsp igg titres timepoints t1 rho058 p0001 t2 rho059 p0001 t3 rho053 p0004 t4 rho047 p001 fng group observed significant correlation humoral response measured t1 t4 treatment duration t1 rho 065 p0001 t2 rho 08 p 0001 t3 rho 072 p0001 t4 rho 067 p0001 ii disease duration t1 rho 05 p0017 t2 rho 06 p0003 t3 rho 058 p0005 t4 rho 057 p0006 iii baseline total lymphocyte count t1 rho 037 p008 t2 rho 045 p003 t3 rho 043 p004 t4 rho 045 p003 conclusions longterm data show weakened shortlasting humoral response sarscov2 mrna vaccine pwms treated ocr fng compared hcs time elapsed since last infusion pwms ocr lymphocyte count well disease treatment duration fng taken account ms neurologists called counsel regarding vaccination sarscov2 mrna vaccine,0.0
abnormal distribution peripheral b1 cells transition b cells patients idiopathic dilated cardiomyopathy pilot study background aberrant distribution peripheral b cell subsets associated pathogenesis variety inflammatory autoimmune diseases however distribution peripheral b cell subsets patients idiopathic dilated cardiomyopathy dcm remains elucidated methodstwentyseven patients idiopathic dcm dcm group 18 control patients heart failure hf group 21 healthy individuals hc group included study peripheral b cell subsets analysed using multicolour flow cytometry plasma 1 adrenergic receptor 1ar autoantibody titre determined using elisa additionally clinical features also collectedresultscompared hf hc groups percentage b1 cells significantly decreased whereas percentage transitional b cells tr significantly increased dcm group notably percentage b1 cells significantly lower patients 1ar autoantibodypositive dcm 1ar autoantibodynegative patients correlation analysis showed percentage b1 cells negatively correlated nterminal probrain natriuretic peptide ntprobnp levels positively correlated left ventricular ejection fraction patients dcmconclusionas shown present study percentage b1 cells peripheral blood patients idiopathic dcm abnormally decreased especially 1ar autoantibodypositive patients percentage tr cells significantly increased indicating b1 cells tr cells may implicated pathogenesis idiopathic dcm decrease percentage b1 cells directly related severity dcm,0.0
combining supervised homebased taskoriented circuit training improves walking endurance patients multiple sclerosis ms_toct randomizedcontrolled trial abstractbackgroundbalance mobility impairments widespread patients multiple sclerosis pwms even early stage can contribute disability physical deconditioning reduced quality life taskoriented training modality may promote walking abilities conditioning however effects usually shortlasting exercising home can several barriers randomized controlled trial aimed test effectiveness combination 2weeks inperson supervised taskoriented circuit training toct followed 12weeks homebased taskoriented program monthly inperson visitsmethods36 pwms edss 455 unassisted walking randomly assigned 10 supervised toct sessions two weeks phase 1 followed 12weeks homebased taskoriented program phase 2 delayedtreatment group end phase 2 delayedtreatment group usual care received toct protocol phase 1 composed six gaitbased workstations treadmill training whereas phase 2 based progressive taskoriented tasks practice home monthly visits adjust activities levels six minute walk test 6mwt timed 25foot walk test t25fw timed go test tug dynamic gait index dgi modified fatigue impact scale mfis multiple sclerosis walking scale 12 msws12 multiple sclerosis impact scale29 msis29 resting muscle oxygen consumption rmvo2 assessed outcome measures baseline phase 1 phase 2 retention tested whole sample 12weeks followupresultsthe entire sample completed 2weeks toct whereas adherence good 12weeks homebased taskoriented program 62 10 mean repetitions level difficulty task significantly increased every timepoint superiority taskoriented program verified 6mwt f 2 88780 p0001 usual care 12weeks homebased program moreover betweengroup differences highlighted point even t25fw tug msws12 rmvo2 fatigue significantly improved experimental group positive effects 6mwt retained 12 weeks end protocol p0001 whole sampleconclusionsthe combination supervised selfmanaged taskoriented program enhances walking endurance positive effects walking ability fatigue resting muscle oxygen consumption pwms unassisted walking preliminary results reflected intervention effective impairment activity improvements moreover cardiorespiratory stressful possibly reduced deconditioningkeywords taskoriented circuit multiple sclerosis endurance home rehabilitation muscle oxygen consumption,0.0
measurement prothrombin fragment 1+2 cerebrospinal fluid identify thrombin generation inflammatory central nervous system diseases abstractbackgroundthe interaction central nervous system inflammation coagulation system activation multiple sclerosis ms receives increasing attention diagnostic therapeutic potential bloodbrain barrier bbb disruption fibrinogen migrates cns contributes inflammation coagulation cascade fibrinogen converted fibrin thrombin cleaved prothrombin activated factor xii hypothesized conversion prothrombin thrombin can quantified prothrombin fragment 1+2 pf12 cerebrospinal fluid csf primary endpoint correlation pf12 ddimer fibrinogen csf patients neuroinflammatory diseases secondary endpoints pf12 levels depending presence contrast enhancement ce mri correlation pf12 serumcsf albumin quotient qalb additionally exploratory analysis csf pf12 levels distinguish mspatients controls without neurological disease performedmethodspatients admitted suspected inflammatory cns disease prospectively recruited october 2017 december 2020 citrated csf samples obtained analyzed pf12 fibrinogen ddimer using ahighly sensitive luminescent oxygen channeling immunoassay patient clinical data final diagnoses retrospectively collected analyzedresults187patientswere included 116 received diagnoses relapsingremitting rrms primaryprogressive ms clinically radiologically isolated syndrome antiaquaporin4 antimyelinoligodendrocyteglycoproteinantibodyrelated diseases csf analysis 116 patients revealed correlation pf12 csf fibrinogen 315 p001 well pf12 csf ddimer 531 p001 among 187 patients csf pf12 increased patients ce mri n71 14738 pmol l iqr 836821536 compared patients without ce n86 10003 pmol l iqr 338716280 p008 csf pf12 correlated significantly qalb 445 p001 differences csf pf12 levels observed rrms 13148 pmol l iqr 427520410 disease controls 10228 pmol l iqr 556015994 p606 conclusionin patients autoimmune inflammatory cns diseases pf12 correlated strongly fibrinogen ddimer csf indicating coagulation system activation findings suggest thrombin generation might require acute bbb dysfunction exert autoimmune effects cns,1.0
drugfree nanozyme mitigating oxidative stress inflammatory bowel disease abstractinflammatory bowel disease ibd incurable disease gastrointestinal tract lack effective therapeutic strategies proinflammatory microenvironment plays significant role amplifying sustaining inflammation ibd progression herein biocompatible drugfree ceria nanoparticles cenppeg regenerable scavenging activities multiple reactive oxygen species ros developed cenppeg exerted therapeutic effect dextran sulfate sodium dss induced colitis murine model evidenced corrected disease activity index restrained colon length shortening improved intestinal permeability restored colonic epithelium disruption cenppeg ameliorated proinflammatory microenvironment persistently scavenging ros downregulating levels multiple proinflammatory cytokines restraining proinflammatory profile macrophages th1 th17 response underlying mechanism may involve restraining coactivation nfb jak2 stat3 pathways summary work demonstrates effective strategy ibd treatment ameliorating selfperpetuating proinflammatory microenvironment offers new avenue treatment inflammationrelated diseasesgraphical abstract,0.0
calmodulin binding proteins neuroinflammation multiple neurodegenerative diseases abstractcalcium dysregulation calcium hypothesis early critical event alzheimers neurodegenerative diseases calcium binds regulates small regulatory protein calmodulin turn binds regulates several hundred calmodulin binding proteins initial continued research shown many calmodulin binding proteins mediate multiple events onset progression alzheimers disease thus establishing calmodulin hypothesis gain insight general applicability hypothesis involvement calmodulin neuroinflammation alzheimers amyotrophic lateral sclerosis huntingtons disease parkinsons disease frontotemporal dementia dementias explored literature search calmodulin binding 11 different neuroinflammatory proteins trem2 cd33 pilra cr1 ms4a clu abca7 epha1 abca1 ch3l1 ykl40 nlrp3 scanned calmodulin binding domains using calmodulin target database analysis revealed presence least one binding domain within visual scanning demonstrated presence valid binding motifs coupled previous research identified 13 neuroinflammation linked proteins bace1 bin1 camkii pp2b pmca nos nmdar achr ado a2ar apoe snca tmem175 work shows least 24 critical proteins involved neuroinflammation putative proven calmodulin binding proteins many proteins linked multiple neurodegenerative diseases indicating calmodulin binding proteins lie heart neuroinflammatory events associated multiple neurodegenerative diseases since many calmodulinbased pharmaceuticals successfully used treat huntingtons neurodegenerative diseases findings argue immediate therapeutic implementation,0.0
covid19 vaccine hesitancy iranian patients multiple sclerosis abstractbackground world health organization mentioned covid19 vaccination safest way eradicate pandemic meantime vaccine hesitancy delay accepting rejecting vaccine despite despite availability vaccination services barrier hence studied obstacle iranian multiple sclerosis ms populationobjective ms patients eligible vaccination asked complete google form survey demographic information ms diseaserelated factors flu vaccination history covid19 vaccination history cause vaccination refusal past history covid19 infection compliance public health guidelines vaccination recordedresults 1479 patients participated study 69 participants received vaccination sinopharm commonly used vaccine 929 vaccine hesitancy associated young age lower education unemployment negative flu vaccination history previous episode covid19 infection less concern covid19 expectation getting infected virus vaccination participants mentioned concerns side effects vaccines prevalent cause avoiding vaccination 580 patientsnull concern sarscov2 significantly decreased vaccination pvalue 0001 conclusion findings study elucidate minor group patients ms vaccine hesitancy may expose severe covid 19 treating physicians ask history vaccination try persuade patients scientific knowledge transformation longterm consequences vaccinated clarified patients especially receiving immunosuppressive agents,0.0
hornerin deposits neuronal intranuclear inclusion disease direct identification proteins compositionally biased regions inclusions abstractneuronal intranuclear inclusion disease niid neurodegenerative disorder characterized presence eosinophilic inclusions niis within nuclei central peripheral nervous system cells study aims identify components niis difficult analyze directly due insolubility order establish method directly identify components niis first analyzed huntingtin inclusionrich fraction obtained brains huntington disease model mice although sequence expanded polyglutamine identified liquidchromatography mass spectrometry amino acid analysis revealed glutamine huntingtin inclusionrich fraction increased significantly compatible calculated amino acid content transgene product therefore applied method analyze niis diseased human brains may proteins compositionally biased regions identified serinerich protein called hornerin since analyzed niirich fraction also serinerich suggested hornerin major component niis specific distribution hornerin niid also investigated matrixassisted laser desorption ionization imaging mass spectrometry immunofluorescence finally confirmed variant hornerin wholeexome sequencing dna sequencing study suggests hornerin may related pathological process niid direct analysis niis especially amino acid analysis using niirich fractions contribute deeper understanding disease pathogenesis,0.0
spatiotemporal parameters gait variability people psoriatic arthritis psa crosssectional study background foot involvement major manifestation psoriatic arthritis psa can lead severe levels foot pain disability impaired functional mobility quality life gait spatiotemporal parameters stps gait variability used clinical index gait stability associated several adverse health outcomes including risk falling functional decline mortality wide range populations previous studies showed alterations stps people psa however gait variability relationships stps gait variability selfreported foot pain disability never studied populations bodyworn inertial measurement units imus gaining interest measuring gait parameters clinical settingsobjectivesto assess stps gait variability people psa using imus explore relationship selfreported foot pain function investigate feasibility using imus discriminate patient groups based gait speedcritical valuesmethodstwentyone participants psa age 539 89 yrs median disease duration 6 yrs 21 age sexmatched healthy participants age 5423 93 yrs recruited participants performed three 10m walk test trials comfortable speed stps gait variability recorded calculated using six bodyworn imus mobility lab software apdm foot pain disability assessed participants psa using foot function index ffi resultscadence gait speed stride length swing phase significantly lower double support significantly higher psa group p 0006 strong correlations stps ffi total score demonstrated r 057 p 0006 gait variability significantly increased psa group correlated foot pain function p 0006 using imus three subgroups participants psa clinically meaningful differences selfreported foot pain disability discriminatedconclusionstps significantly altered participants psa associated selfreported foot pain disability future studies required confirm increased gait variability highlighted study potential underlying causes using imus useful objectively assess foot function people psatrial registrationclinicaltrialsgov nct05075343 retrospectively registered 29 september 2021,0.0
erap1 critical regulator inflammasomemediated proinflammatory er stress responses background addition role antigen presentation recent reports establish new role endoplasmic reticulum aminopeptidase 1 erap1 innate immunity however mechanisms underlying functions fully defined previously confirmed loss erap1 functions resulted exaggerated innate immune responses murine vivo model investigated role erap1 suppressing inflammasome pathways dependence er stress responsesresultsusing bone marrowderived macrophages bmdms found loss erap1 macrophages resulted exaggerated production il1 il18 augmented caspase1 activity relative wild type macrophages moreover vivo colitis model utilizing dextran sodium sulfate dss confirmed increased levels proinflammatory cytokines chemokines colon dss treated erap1 mice compared identically stimulated wt mice interestingly stimulated erap1 bmdms cd4+ t cells simultaneously demonstrated exaggerated er stress assessed increased expression er stressassociated genes state reverted wt levels use er stress inhibitor tauroursodeoxycholic acid tudca conclusionstogether results suggest erap1 important regulating inflammasome dependent innate immune response pathways vivo also propose mechanism underlies changes may associated increased er stress due lack normal erap1 functions,0.0
perfect match mtor inhibitors tuberous sclerosis complex abstracttuberous sclerosis complex tsc autosomal dominant syndrome presents diverse complex clinical features involves multiple human systems tscrelated neurological abnormalities organ dysfunction greatly affect quality life can even result death patients tsc widely accepted tscrelated clinical manifestations associated hyperactivation mammalian target rapamycin mtor pathway caused lossoffunction mutations tsc1 tsc2 remarkable progress basic translational research led encouraging clinical advances although mtor inhibitors rapamycin everolimus demonstrate great potential tsc management two major concerns hamper generalized application one frequent manifestation adverse events stomatitis infections menstrual disorders poor response certain patients thus indicators required effectively predict efficacy mtor inhibitors herein summarized current utilization mtor inhibitors treatment tsc focused efficacy safety attempt provide reference guide treatment tsc,0.0
improving clinical trial readiness accelerate development new therapeutics rett syndrome abstractrett syndrome associated severe functional impairments many comorbidities urgent need treatments mutations mecp2 gene identified causing rett syndrome 1999 past 20 years abundance preclinical research studies leading human clinical trials despite viable therapeutic options emerged investment effort reasons lack success relate preclinical research clinical trial landscape discussed considering needs done promote success field take positive constructive approach introduce concept clinical trial readiness necessary ingredients rett syndrome include listening needs families support advocacy groups optimising use existing clinic infrastructures available natural history data finally validation existing outcome measures development validation new measures conclude reiterating need collaborative coordinated approach amongst many different stakeholder groups need engage new types trial design much efficient less costly much less burdensome families,0.0
pathways cures multiple sclerosis research roadmap mult scler 2022 mar 28 3 331345 doi 101177 13524585221075990abstractbackground multiple sclerosis ms growing global health challenge affecting nearly 3 million people progress made understanding treatment ms last several decades cures remain elusive national ms society focused achieving cures msobjectives cures ms will hastened roadmap describes knowledge gaps milestones research priorities report share pathways cures research roadmap recommendations strategies accelerate development ms curesmethods roadmap developed engagement scientific thought leaders people affected ms north america united kingdom also included perspectives 300 people living ms endorsed many leading ms organizationsresults roadmap consist three distinct overlapping cure pathways 1 stopping ms disease process 2 restoring lost function reversing damage symptoms 3 ending ms prevention better alignment focus global resources high priority research questions also recommendedconclusions hope roadmap will inspire greater collaboration alignment global resources accelerate scientific breakthroughs leading cures mspmid35236198 doi101177 13524585221075990,1.0
effect diseasemodifying treatments antibodymediated response anticovid19 vaccination people multiple sclerosis j neurol 2022 mar 3 doi 101007 s00415022110033 online ahead printabstractbackground data available far antibodymediated immune response antisarscov2 vaccination people multiple sclerosis pwms treated diseasemodifying treatments dmts therefore issue explored reallife cohort pwmsmaterials methods retrospective monocentric study antispike protein antibody response pwms received vaccination sarscov2 adverse events following vaccination also recordedresults one hundred twenty pwms included 83 females 69 median age vaccination 42 years range 2173 112 120 patients 93 receiving dmts vaccination antispike protein igg antibodies detectable 102 120 85 cases overall proportion lower pwms receiving anticd20 antibodies 14 31 45 compared nondepletive treatments 77 78 99 p 00001 median antispike titre lower anticd20 antibodies fingolimodtreated pwms compared receiving dmts correlated anticd20 treatment duration r 093 p 00001 age vaccination pwms receiving depletive treatments r 025 p 0028 baseline cd19+ cell count available higher responder group nonresponders p 00001 two symptomatic covid19 infections diagnosed median followup 5 months range 27 adverse events aligned published literatureconclusion antibody response anticovid19 vaccines detected pwms analysed frequency responders reduced receiving cd20 depleting therapies compared dmtstreated pwms investigations cellmediated immune response needed assess whether protective immune response elicited also nonantibody responderspmid35239006 doi101007 s00415022110033,0.0
disabled society scoping review persons living multiple sclerosis disability j multidiscip healthc 2022 feb 24 15375390 doi 102147 jmdhs353347 ecollection 2022abstractmultiple sclerosis ms chronic neurological disease increasing prevalence studies devoted various medical aspects disease theoretical framework used scoping review social model disability perspective focusing environmental barriers discrimination disabled people face society aim explore previous research disabling barriers discrimination persons ms identify research gaps connection population scoping review performed two steps 1 main search 8 databases followed 2 citation reference searches final sample consisted 96 included articles result showed studies conducted us dominant area research employment discrimination previous research studied ms related various areas employment social welfare social services transportation housing accessibility public places health services relation others within society however scoping review showed although several areas disability ms included previous research identified areas researched studies without possibility generalize findings larger population crosscultural context studies compared differences persons ms based gender age ethnicity impact invisible symptoms ms disability also researched limited extent findings implications future research clinical practice better understand living conditions persons ms global perspective research across countries needed healthcare professionals need assess individuals situation regarding symptoms disease impact societal barriers discrimination optimize care persons mspmid35237043 pmcpmc8884705 doi102147 jmdhs353347,0.0
susac syndrome unique involvement thoracic spinal cord bmj case rep 2022 mar 2 15 3 e247351 doi 101136 bcr2021247351abstracta woman late 20s presented headaches subacute encephalopathy mris showed multiple punctate subcortical periventricular white matter hyperintensities diffusion restriction infratentorial lesions leptomeningeal enhancement cervical spinal cord brainstem cerebellum two areas highsignal abnormality t4 t6 raising suspicion multiple sclerosis acute disseminated encephalomyelitisfurther studies evolution symptoms hospital stay confirmed clinical triad encephalopathy branch retinal artery occlusions hearing loss pathognomonic susacs syndromewhile cervical spinal cord cauda equina involvement reported susacs syndrome previously thoracic spinal cord involvement reportedwe report novel mri finding thoracic spinal cord involvement susacs syndrome order avoid misdiagnosis neurologists neuroradiologists aware part spinal cord can involved susacs syndromepmid35236690 doi101136 bcr2021247351,0.0
hungarian multiple sclerosis care units fulfil international criteria plos one 2022 mar 3 17 3 e0264328 doi 101371 journalpone0264328 ecollection 2022abstracta patients past 3 decades extensive research several disease modifying therapies became available thus paradigm change multiple sclerosis care necessary 2018 therapeutic guideline created recommending treatment persons multiple sclerosis take place specified care units entire spectrum disease modifying therapies available patient monitoring ensured therapy side effects detected treated promptly 2019 multiple sclerosis care unit criteria developed emphasizing personnel instrumental requirements provide professional care however survey conducted assessing realworld adaptation criteriaobjective assess whether hungarian care units fulfil international criteriamethods selfreport questionnaire assembled based international guidelines sent hungarian care units focusing 3 main aspects personnel instrumental background diseasemodifying therapy use number people living multiple sclerosis receiving care care units data number persons multiple sclerosis compared hungarian prevalence estimates descriptive statistics used analyse dataresults 27 respondent care units 3 fulfilled minimum requirements 7 fulfilled minimum recommended requirements least prevalent neighbouring specialties spasticity pain specialist neuroophthalmologist otoneurologist 15 centres used available disease modifying therapies total number 7213 people multiple sclerosis received care 27 respondent centres compared prevalence estimates 2500 persons multiple sclerosis receive multiple sclerosis specific care hungaryconclusion less half hungarian care units provided sufficient care people living multiple sclerosis care units employing fewer neighbouring specialties might difficulties diagnosing providing appropriate care persons multiple sclerosis especially people progressive disease course contributing reported low number persons living multiple sclerosispmid35239686 doi101371 journalpone0264328,0.0
exerciseinduced increase bloodbased brainderived neurotrophic factor bdnf people multiple sclerosis systematic review metaanalysis exercise intervention trials plos one 2022 mar 3 17 3 e0264557 doi 101371 journalpone0264557 ecollection 2022abstractbackground exercise training may affect blood levels brainderived neurotrophic factor bdnf metaanalyses yet performed comparing pre postintervention bdnf concentrations patients multiple sclerosis pwms objective perform metaanalysis study influence exercise bdnf levels define components modulate across clinical trials exercise training adults living multiple sclerosis ms method five databases pubmed embase cochrane library pedro database cinahl searched june 2021 according preferred reporting items systematic reviews metaanalyses included 13 articles metaanalysis including 271 subjects investigate sources heterogeneity subgroup analysis metaregression sensitivity analysis conducted performed metaanalysis compare pre postexercise peripheral levels bdnf pwmsresults postexercise concentrations serum bdnf significantly higher preintervention levels standardized mean difference smd 033 95 ci 004 061 pvalue 002 metaregression indicated quality included studies based pedro assessment tool might source heterogeneity significant effect found chronological age disease severity according expanded disability status scaleconclusion systematic review metaanalysis shows physical activity increases peripheral levels bdnf pwms research effect different modes exercise bdnf levels pwms warrantedpmid35239684 doi101371 journalpone0264557,0.0
possible causal involvement neuroinflammatory purinergic p2x7 receptors psychiatric disorders curr neuropharmacol 2022 mar 2 doi 102174 1570159x20666220302152400 online ahead printabstractp2x7 receptors rs prominent members p2xr family binding atp open nonselective cationic channels allowing transmembrane passage na+ ca2+ k+ longlasting repetitive stimulation receptor agonist leads formation large membrane pores permeable organic cations 900 da molecular size pores believed play role apoptosis inflammation p2x7rs located primarily peripheral macrophages microglial cells resident macrophages cns coactivation tolllike receptors 4 tlr4 lipopolysaccharide constituent cell membrane gram negative bacteria p2x7r atp leads generation release proinflammatory cytokines interleukin1 il1 il6 tumor necrosis factor cytokines together microglial release chemokines reactive oxygen nitrogen species proteases also excitotoxic glutamate results neurodegeneration p2x7rs found amplify various neurodegenerative illnesses alzheimers disease parkinsons disease amyotrophic lateral sclerosis multiple sclerosis also participate range psychiatric diseases major depression bipolar disorder schizophrenia autism spectrum disorder based prevention reversal neuroinflammation pharmacological antagonists p2x7rs genetic deletion animal experiments counteracts deleterious psychiatric conditions hence brain penetrant p2x7r antagonists potential therapeutics psychiatric diseases although available evidence still needs extended validated clinical datapmid35236262 doi102174 1570159x20666220302152400,0.0
associations alcohol consumption smoking disease risk neurodegeneration individuals multiple sclerosis united kingdom jama netw open 2022 mar 1 5 3 e220902 doi 101001 jamanetworkopen20220902abstractimportance understanding effects modifiable risk factors risk multiple sclerosis ms associated neurodegeneration important guide clinical counselingobjective investigate associations alcohol use smoking obesity odds ms diagnosis macular ganglion cell layer inner plexiform layer mgcipl thicknessdesign setting participants crosssectional study analyzed data communitybased uk biobank study health behaviors retinal thickness measured optical coherence tomography eyes individuals aged 40 69 years examined december 1 2009 december 31 2010 risk factors identified multivariable logistic regression analyses adjust intereye correlations multivariable generalized estimating equations used explore associations alcohol use smoking mgcipl thickness finally interaction models explored whether correlations alcohol smoking mgcipl thickness differed individuals ms data analyzed february 1 july 1 2021exposures smoking status never previous current alcohol intake never special occasions low per month 4 times per week moderate daily almost daily high body mass indexmain outcomes measures multiple sclerosis case status mgcipl thicknessresults total 71 981 individuals 38 685 women 537 33 296 men 463 mean sd age 567 80 years included analysis 20 065 healthy control individuals 51 737 control individuals comorbidities 179 individuals ms modifiable risk factors significantly associated ms case status current smoking odds ratio 305 95 ci 195464 moderate alcohol intake 062 95 ci 043091 obesity 172 95 ci 115256 compared healthy control individuals compared control individuals comorbidities smoking associated case status 230 95 ci 148351 high alcohol intake associated thinner mgcipl individuals ms adjusted 309 95 ci 570 048 m p 02 alcohol interaction model high alcohol intake associated thinner mgcipl control individuals 093 95 ci 107 079 m p 001 statistically significant association individuals ms 227 95 ci 476 022 m p 07 smoking associated mgcipl thickness ms however smoking associated greater mgcipl thickness control individuals 089 95 ci 074105 m p 001 conclusions relevance findings suggest high alcohol intake associated retinal features indicative severe neurodegeneration whereas smoking associated higher odds diagnosed mspmid35238934 doi101001 jamanetworkopen20220902,0.0
detection antinmda receptor antibodies following bbibpcorv covid19 vaccination rituximabtreated person multiple sclerosis presenting manifestations acute relapse hum vaccin immunother 2022 mar 314 doi 101080 2164551520222033540 online ahead printabstractantinmethyldaspartate receptor nmdar encephalitis relatively unknown autoimmune entity scant reports postinfection vaccination antinmdar encephalitis exist hereby reviewed relevant cases added literature possible case antinmdar encephalitis following covid19 vaccination bbibpcorv sinopharm 50yearold persian woman previously known rituximabtreated ms presented complaining worsening neurological symptoms gradually starting worsening receiving second dose bbvipcorv 2 weeks notable findings physical examination included ataxic gait babinski sign considering acute ms relapse corticosteroid pulse therapy initiated referred mri revealed multiple new plaques serum sample interestingly tested positive antinmdar antibodies csf analysis unfortunately performed responded well corticosteroid pulse therapy showed substantial resolution symptoms considering relatively low cost workup benefits correct early diagnosis clinicians advised consider autoimmune encephalitis encountering patients progressive neurological symptoms administration vaccines including ones covid19 currently used extensivelypmid35239452 doi101080 2164551520222033540,0.0
visual search naturalistic scenes reveals impaired cognitive processing speed multiple sclerosis front neurol 2022 feb 14 13838178 doi 103389 fneur2022838178 ecollection 2022abstractbackground standardized neuropsychological testing serves quantify cognitive impairment multiple sclerosis ms patients however exact mechanism underlying translation cognitive dysfunction difficulties everyday tasks remained unclear answer question tested ms patients intact vs impaired information processing speed measured symbol digit modalities test sdmt differ visual search behavior ecologically valid tasks reflecting everyday activitiesmethods fortythree patients relapsingremitting ms enrolled eyetracking experiment consisting visual search task naturalistic images patients grouped impaired unimpaired according sdmt performance reaction time accuracy eyetracking parameters measuredresults groups differ regarding age gender visual acuity patients impaired sdmt cutoff sdmtzscore 15 performance needed time find fixate target q 0006 spent less time fixating target q 0042 impaired patients slower reaction times less accurate q 00495 even controlling patients upper extremity function exploratory analysis revealed unimpaired patients higher accuracy impaired patients particularly announced target unexpected location p 0037 correlational analysis suggested sdmt performance inversely linked time first fixation target announced target expected location r 0498 p 0003 vs r 0212 p 0229 conclusion dysfunctional visual search behavior may one mechanisms translating cognitive deficits difficulties everyday tasks ms patients results suggest cognitively impaired patients search visual environment less efficiently particularly evident topdown processes employedpmid35237231 pmcpmc8884171 doi103389 fneur2022838178,0.0
nicatalyzed crosscoupling 2iodoglycals 2iodoribals grignard reagents route 2cglycosides 2cnucleosides chemistry 2022 mar 2 doi 101002 chem202104311 online ahead printabstractthe synthesis 2 c glycals 2 c ribals achieved good yields using nickelcatalyzed crosscoupling 2iodoglycals 2iodoribal respectively grignard reagents prepared 2 c glycals ribals transformed 2 c 2deoxyglycosides 2 c diglycosides 2 c 2deoxynucleosides developed method applied synthesis 2chloroadenine 2deoxyribonucleoside structural analogue cladribine mavenclad leustatin clofarabine clolar evoltra two compounds used treatment relapsingremitting multiple sclerosis hairy cell leukemiapmid35238093 doi101002 chem202104311,0.0
mogspecific t cells lead spontaneous eae multilocular b cell infiltration gfil23 model neuromolecular med 2022 mar 3 doi 101007 s12017022087052 online ahead printabstractalthough il23 downstream signal transduction play essential roles neuroinflammation local impact il23 multiple sclerosis still fully understood previous study revealed central nervous system cns restricted expression il23 mouse model astrocytespecific expression il23 called gfil23 mice leads spontaneous formation infiltrates brain especially cerebellum investigate impact cnsspecific il23expression neuroinflammation studied gfil23 model mice expressing myelin oligodendrocyte glycoprotein mog specific t cell receptor gf232d2 mice gf232d2 mice developed chronic progressive experimental autoimmune encephalomyelitis myelitis ataxia without requiring additional immunization cnsproduction il23 alone induced pronounced neuroinflammation transgenic mogspecific t cell receptor model gf232d2 mice spontaneously developed multilocular infiltrates high number b cells demyelination proinflammatory cytokine milieu indicating interaction encephalitogenic t cells b cells via costimulatory factors seemed crucialpmid35239103 doi101007 s12017022087052,1.0
tuberous sclerosis complex novel amyloidindependent tauopathy associated elevated phosphorylated 3r#x2f 4r tau aggregation abstracttuberous sclerosis complex tsc neurodevelopmental disorder caused mutations tsc1 tsc2 genes autosomal dominantly inherited mutations cause hyperactivation mammalian target rapamycin mtor pathway leading development nonmalignant masses involving various organ systems patients tsc also experience neuropsychiatric symptoms collectively termed tuberous sclerosis complex associated neuropsychiatric disorder tand due research advancements tsc patients now live well beyond age 50 many experience objective impairment memory executive function supported formal neuropsychological testing beginning late 40s biomarker analysis described elevated levels phosphorylated tau181 cerebrospinal fluid patients tand taupet imaging also shown focal accumulation radiotracer flortaucipir av1451 suggesting tsc may neurodegenerative disorder arising accumulation phosphorylated tau however flortaucipir tracer reported significant offtarget binding preventing definitive conclusions drawn molecular etiology neurodegeneration tsc therefore initiated colocalization av1451 phosphorylated tau adult brain tissue capa study study aimed determine flortaucipir bound phosphorylated tau brains patients tsc sought determine specific tau isoform seen tsc results show flortaucipir labels 3r 4r isoform phosphorylated tau commonly seen alzheimers disease however amyloid staining negative brains adult patients tsc therefore conclude tand symptoms due accumulation phosphorylated tau isoform seen alzheimers disease study suggests hyperactivation mammalian target rapamycin pathway may play role amyloidindependent development 3r 4r tau aggregation findings lead new era antitau therapies used treat disorders,0.0
medical marijuana knowledge attitudes amongst internal medicine residents background mounting evidence suggests safety efficacy medical marijuana mm treating chronic ailments including chronic pain epilepsy anorexia despite incremental use medical recreational cannabinoids current limited evidence shows generalized unpreparedness medical providers discuss recommend substances patients herein present study aims examine internal medicine residents knowledge marijuana attitude towards medical usemethodsthis descriptive crosssectional study survey 12 standardized queries created distributed among internal medicine residents mount sinai morningsidewest msmw program july 2020 december 2020 participants included preliminary categorical residents postgraduate years one three survey consisted selfassessment residents knowledge indication contraindication adverse effects mmresultseightysix 59 145 residents completed questionnaire despite trainees 70 considered certifying use mm patients 90 reported none little knowledge use approximately 80 surveyed residents expressed willingness receive appropriate educational curriculumconclusionto best knowledge first study indicated critical lack medical marijuanarelated knowledge surveyed internal medicine residents population growing cannabis consumption physician training indication toxicity drug interaction cannabinoids warranted,0.0
amp5a modulates tolllike receptors 7 8 singlestranded rna immune responses pmadifferentiated thp1 pbmc background dysregulation antiviral immunity implicated progression acute respiratory syndrome coronavirus 2 infection severe cases coronavirus disease 2019 covid19 imbalances inflammatory response drive overabundant production proinflammatory cytokines chemokines low molecular weight fraction 5 human serum albumin commercial preparation amp5a novel biologic drug currently clinical investigation treatment osteoarthritis hyperinflammatory response associated covid19 study aims elucidate amp5a effects following activation immune cells agonists tolllike receptor tlr 7 8 detect ssrna viral sequencesmethodscxcl10 elisas used evaluate dynamics myeloid cells activated cl075 cl307 agonists tlr7 8 tlr7 respectively addition enrichment analysis gene sets generated elisa arrays utilized gain insight biologic processes underlying identified differentially expressed cytokine profiles finally relative potency rep employed confirm involvement mechanisms action paramount amp5a activityresultsamp5a inhibits release cxcl10 cl075 cl307activated pmadifferentiated thp1 peripheral blood mononuclear cells furthermore amp5a suppresses distinct set proinflammatory cytokines including il1 il6 il12 cxcl10 associated covid19 proinflammatory nfb activation rep experiments using antagonists specific immunomodulatory transcription factors peroxisome proliferatoractivated receptor aryl hydrocarbon receptor also indicate pathways involved ability amp5a inhibit cxcl10 releaseconclusiondue biphasic course covid19 therapeutic approaches augment antiviral immunity may beneficial early infection whereas later interventions focus inflammation suppression study show amp5a inhibits tlr 7 8 signaling myeloid cells resulting decrease inflammatory mediators associated hyperinflammation autoimmunity furthermore data demonstrating amp5a activates immunomodulatory transcription factors found protective lung disease provided findings suggest modes mechanisms action amp5a well suited treat conditions involving dysregulated tlr 7 8 activationgraphical abstract,0.0
functional standing frame programme early severe subacute stroke spires randomised controlled feasibility trial background early mobilisation 24 h poststroke recommended people stroke however paucity evidence implement early mobilisation people severe stroke prolonged standing taskspecific training sittostand repetitions separately evaluated literature however functionally linked tasks evaluated combination people severe subacute strokemethodsthe objective determine feasibility conducting randomised controlled trial rct functional standing frame programme compared usual physiotherapy people severe subacute stroke assessorblinded feasibility rct nested qualitative component interviews focus group process evaluation adopted participants aged 18 years new diagnosis severe subacute stroke modified rankin scale mrs 4 5 four stroke rehabilitation units across south west england participants randomised receive either 1 functional standing frame programme 30 min standing plus sittostand repetitions plus 15 min usual physiotherapy daily intervention 2 usual physiotherapy 45 min daily control programmes protocolised undertaken minimum five sessions per week 3 weeksfeasibility indicators included process resource management safety adherence fidelity acceptability trial intervention evaluated using data recorded therapists observation intervention control sessions interviews one focus group patient measures motor impairment activities participation quality life carried blinded assessors baseline 3 15 29 55 weeks postrandomisationresultsfortyfive participants 5196 years 42 male mrs 4 80 5 20 randomised n 22 intervention twentyseven 60 participants followedup time points twelve participants 27 died trial deaths related trial adherence minimum number sessions low none participants completed 21 sessions 8 participants 18 across groups completed 15 sessions 3 weeks 39 intervention 51 control sessions completed mean session duration 39 min sd 19 control 37 min intervention sd 11 intervention group mean standing time 13 min sd 9 mean sittostand repetitions session 5 sd 4 interviews conducted 10 participants four relatives six physiotherapists five physiotherapists attended focus groupconclusionsthe majority progression criteria feasibility trial met however adherence interventions unacceptably low aspect trial design needs addressed prior moving definitive rct standing frame intervention people severe subacute stroke solutions identified address concernstrial registrationinternational standard randomised controlled trial number isrctn15412695 registration 19 december 2016,0.0
systematic umbrella review association prescription drug insurance costsharing drug use health services use health background increasing spending use prescription drugs pose important challenge governments seek expand health insurance coverage improve population health controlling public expenditures patient costsharing deductibles coinsurance widely used aim control healthcare expenditures without adversely affecting healthmethodswe conducted systematic umbrella review quality assessment included studies examine association prescription drug insurance costsharing drug use health services use health searched five electronic bibliographic databases handsearched eight specialty journals two working paper repositories examined references relevant reviews least two reviewers independently screened articles extracted characteristics methods main results assessed quality included studyresultswe identified 38 reviews found consistent evidence drug insurance lower costsharing among insured associated increased drug use lack loss drug insurance higher drug costsharing associated decreased drug use also found consistent evidence poor chronically ill seniors children similarly responsive changes insurance costsharing found drug insurance lower drug costsharing associated lower healthcare services utilization including emergency room visits hospitalizations outpatient visits find consistent evidence association drug insurance costsharing health lastly find evidence association drug insurance costsharing drug use health services use health differed socioeconomic status health status age sexconclusionsgiven poor nearpoor often report substantially lower drug insurance coverage universal pharmacare likely increase drug use among lowerincome populations relative higherincome populations net probable health services use decrease universal pharmacare among gain drug insurance crossprice effects extending drug coverage included costing simulations,0.0
fam167a key molecule induce bcrablindependent tki resistance cml via noncanonical nfb signaling activation background bcrablindependent drug resistance barrier curative treatment chronic myeloid leukemia cml however molecular pathways underlying bcrablindependent tyrosine kinase inhibitor tki resistance remain unclearmethodsin silico bioinformatic analysis performed identify active transcription factor inducer contribute bcrablindependent tki resistance tandem mass spectrometry analysis performed identify receptor noncanonical nfb activator fam167a vitro vivo mouse experiments revealed detailed molecular insights functional role fam167adesmoglein1 dsg1 axis bclablindependent tki resistance cml cells derived cml patients analyzed using quantitative reverse transcription pcr flow cytometryresultswe found nfb greatest effect differential gene expression bcrablindependent tkiresistant cml cells moreover found previously uncharacterized protein fam167a activates noncanonical nfb pathway induces bcrablindependent tki resistance molecular analyses revealed fam167a activates noncanonical nfb pathway binding cell adhesion protein dsg1 upregulate nfbinducing kinase nik blocking ubiquitination neutralization fam167a mouse tumor model reduced noncanonical nfb activity restored sensitivity cells tkis furthermore fam167a surface dsg1 levels highly upregulated cd34+ cml cells patients bcrablindependent tkiresistant diseaseconclusionsthese results reveal fam167a acts essential factor bcrablindependent tki resistance cml activating noncanonical nfb pathway addition fam167a may serve important target biomarker bcrablindependent tki resistance,0.0
osteopontin autoimmune disorders current knowledge future perspective inflammopharmacology 2022 mar 2 doi 101007 s10787022009320 online ahead printabstractosteopontin opn multifunctional cytokine adhesion molecule well unusual regulator innate adaptive immune responses several immune cells can produce opn including dendritic cells dcs macrophages t lymphocytes opn expression reported increased wide range disorders including autoimmunity cancer allergy overexpression opn several autoimmune disorders rheumatoid arthritis ra systemic lupus erythematosus sle multiple sclerosis ms type 1 diabetes t1d inflammatory bowel disease ibd sjgrens myasthenia gravis shown correlated disease severity regarding important regulatory roles opn immune system study aimed review role molecule autoimmune disorders provide complete view current knowledge fieldpmid35235108 doi101007 s10787022009320,0.0
failed remyelination nonhuman primate optic nerve leads axon degeneration retinal damages visual dysfunction proc natl acad sci u s 2022 mar 8 119 10 e2115973119 doi 101073 pnas2115973119 epub 2022 mar 2abstractsignificance promotion remyelination become new therapeutic avenue prevent neuronal degeneration promote recovery white matter diseases multiple sclerosis ms date strategies developed shortlived rodent models demyelination spontaneously repair welldefined nonhuman primate models closer man allow us efficiently advance therapeutic approaches present nonhuman primate model optic nerve demyelination recapitulates several features ms lesions model leads failed remyelination associated progressive axonal degeneration visual dysfunction thus providing missing link translate emerging preclinical therapies clinic myelin disorders mspmid35235463 doi101073 pnas2115973119,1.0
antibody crossreactivity casein myelinassociated glycoprotein results central nervous system demyelination proc natl acad sci u s 2022 mar 8 119 10 e2117034119 doi 101073 pnas2117034119 epub 2022 mar 2abstractsignificance multiple sclerosis ms prevalent autoimmune disease central nervous system cns leading irreversible deficits young adults pathophysiology believed influenced environmental determinants far back 1990s suggested correlation consumption cows milk prevalence ms demonstrate high percentage ms patients harbor antibodies bovine casein also antibody crossreactivity cows milk cns antigens can exacerbate demyelination data broaden current understanding diet influences etiology ms set stage combining personalized diet plans diseasemodifying treatment strategiespmid35235454 doi101073 pnas2117034119,1.0
immune response third covid19 vaccine dose related lymphocyte count multiple sclerosis patients treated fingolimod j neurol 2022 mar 2 doi 101007 s00415022110300 online ahead printabstractbackground majority multiple sclerosis ms patients treated fingolimod fail develop protective level igg humoral adaptive cellular immune responses following full bnt162b2 sarscov2 vaccinationobjective compare efficacy third covid19 vaccine dose vaccine nonresponders fingolimodtreated ms patientsstudy design prospective 3month singlecenter randomized clinical trialmethods twenty relapsing ms patients fingolimod therapy 12 months failed develop humoral igg immune response 2dose pfizer bnt162b2 covid19 vaccination randomized two groups fingolimodcontinuation group fingolimoddiscontinuation group humoral memory cellular immune responses assessed within 1 3 months following third pfizer bnt162b2 vaccine dose compared groupsresults higher rate patients fingolimoddiscontinuation group n 8 10 compared fingolimodcontinuation group n 2 10 developed positive sarscov2 igg median igg titer 1 month following third dose 2023 bau ml vs 264 bau ml respectively p 0022 development igg humoral response correlated absolute lymphocyte count specific sarscov2 memory b cell t cell immune responses detected groups either 1 month 3 months following third covid19 vaccine doseconclusions short period fingolimod treatment discontinuation associated development humoral protection adaptive cellular immunitypmid35235002 doi101007 s00415022110300,0.0
neurological symptoms disorders following electrical injury registerbased matched cohort study plos one 2022 mar 2 17 3 e0264857 doi 101371 journalpone0264857 ecollection 2022abstractintroduction electric shocks may neurological consequences victims although literature neurological consequences electric shocks limited retrospective designs case studies studies selected patient groups previous research provides evidence link electric shocks diseases symptoms central nervous system cns eg epilepsy migraine vertigo peripheral nervous system pns eg loss sensation neuropathy muscle weakness study aims employ registerbased matched cohort study investigate whether individuals demonstrate greater risk neurological diseases symptoms cns pns years following electrical injurymaterials methods identified 14 112 electrical injuries period 19 years two danish registries matched three different groups persons prospective matched cohort study 1 patients dislocation sprain injuries 2 patients eye injuries 3 persons employed occupation year injury sex age used matching variables outcomes identified comprised neurological disorders central peripheral nervous system symptoms covered range diagnoses danish national patient register associations analysed using conditional logistic regression range time periods six months five years conditional cox regression analyses complete followup period 20 years results victims electric shock cns sequelae identified included increased risk epilepsy convulsions abnormal involuntary movements headache migraine vertigo also identified uncertain increased risk spinal muscular atrophy dystonia whereas identified increased risk parkinsons disease essential tremor multiple sclerosis degenerative diseases nervous system victims electric shock pns sequelae identified included increased risk disturbances skin sensation mononeuropathy arm leg nerve root plexus disorders also identified uncertain increased risk facial nerve disorders mononeuropathy polyneuropathyconclusion results confirm electrical injuries increase risk several neurological diseases symptoms cns pns years following injury often diseases symptoms diagnosed within first six months injury delayed onset 5 years ruled symptoms diagnoses conditions rare population limited ability identify associations warrants cautious interpretation therefore studies needed confirm findings studies examine mechanisms underlying associationspmid35235596 doi101371 journalpone0264857,0.0
dietary patterns risk multiple sclerosis results doublecenter casecontrol study iran nutr health 2022 mar 22601060221082379 doi 101177 02601060221082379 online ahead printabstractbackground suggested nutrition might contribute multiple sclerosis etiology ms aim casecontrol study aimed determine role food habits dietary patterns preventing developing ms multicenter study iran tehran shiraz methods study food intake 106 patients relapsing remitting ms rrms 72 healthy controls tehran 75 patients relapsing remitting ms rrms 72 healthy controls shiraz collected using validated semiquantitative food frequency questionnaire dietary patterns extracted using factor analysis association dietary patterns risk ms analyzed logistic regression results two major dietary patterns extracted healthy unhealthy patterns adjustment potential confounders tehran city subjects highest tertile unhealthy dietary pattern score greater odds ms compared lowest tertile 216 95 ci 195241 p trend 001 shiraz city subjects highest tertile unhealthy dietary pattern score greater odds ms lowest tertile 308 95 ci 127738 p trend 001 however groups significant association found healthy dietary pattern ms risk conclusions adherence unhealthy dietary pattern may increase risk ms iran results can used developing interventions aim promote healthy eating preventing mspmid35234101 doi101177 02601060221082379,0.0
adaptive immunity chronic inflammation clock semin immunopathol 2022 mar 1 doi 101007 s00281022009197 online ahead printabstractthe adaptive arm immune system facilitates recognition specific foreign pathogens via action t b lymphocytes induces finetuned response target pathogen develop immunological memory functionality adaptive immune system exhibits daily 24h variation homeostatic processes lymphocyte trafficking development t lymphocyte subsets responses challenge discuss circadian clock exerts influence function adaptive immune system considering roles cell intrinsic clockwork machinery cell extrinsic rhythmic signals inappropriate misguided actions adaptive immune system can lead development autoimmune diseases rheumatoid arthritis ulcerative colitis multiple sclerosis growing evidence indicates disturbance circadian clock negative impact development progression chronic inflammatory diseases examine current understanding clockimmune interactions setting inflammatory conditions greater appreciation circadian control adaptive immunity will facilitate understanding mechanisms driving daily variation disease states drive improvements diagnosis treatment chronic inflammatory diseasespmid35233691 doi101007 s00281022009197,0.0
emergency department use persons ms populationbased descriptive study focus infectionrelated visits mult scler 2022 mar 113524585221078497 doi 101177 13524585221078497 online ahead printabstractwe described emergency department ed visits visits infectionrelated persons multiple sclerosis ms british columbia canada 1 april 2012 31 december 2017 identified 15 350 ms cases using health administrative data 734 women averaging 514 years study entry 49 years followup mean 560 ms cases visited ed mean 06 visits person year total 37 072 visits diagnosis documented 25 698 693 ed visits 184 4725 25 698 infectionrelated inpatient admissions reported 204 5238 25 698 292 1380 4725 infectionrelated ed visits findings suggest ed plays substantial role ms healthcare infection managementpmid35232298 doi101177 13524585221078497,0.0
nephronectin influences eae development regulating th17#x2f treg balance via reactive oxygen species j physiol cell physiol 2022 mar 2 doi 101152 ajpcell003762021 online ahead printabstractblood levels extracellular matrix protein nephronectin npnt protein critical kidney development elevated autoimmune experimental encephalitis eae mice model multiple sclerosis found treatment antinpnt antibody directed 81 integrinbinding site npntfd antibody inhibits eae development selenium transporter selenoprotein p sep identified novel npntbinding partner eae npnt induced sep glutathione peroxidase 1 gpx1 expression followed reactive oxygen species ros inhibition cd4+ t cells changes disturbed npntfd antibody treatment also caused decreased differentiation interleukin il 17producing cd4+ thelper cells th17s increased differentiation regulatory t cells tregs treatment eae mice ros scavenger nacetyl cysteine nac blocked npntfd antibodyinduced decrease th17 differentiation increase treg differentiation conclusion interaction npnt sep contributes eae development regulating th17 treg balance via ros levelpmid35235429 doi101152 ajpcell003762021,0.0
sarscov2 infection novel risk factor multiple sclerosis neuroimmunomodulation 2022 mar 214 doi 101159 000521891 online ahead printabstractthe outbreak novel severe acute respiratory syndrome coronavirus2 sarscov2 challenged healthcare community worldwide sarscov2 primarily affects respiratory system however strong evidence suggests sarscov2 can neuroinvasive resulting several neurological complications previously assumed coronaviruses involved multiple sclerosis ms pathology via various mechanisms mechanisms involved coronavirusinduced central demyelination complex largely redundant molecular mimicry proposed one possible mechanisms disruption bloodbrain barrier dysregulation several inflammatory cytokines upregulation matrix metalloproteinases also thought induce central demyelinating pathology raises question possible role sarscov2 novel risk factor mspmid35235939 doi101159 000521891,1.0
automated method precise axon reconstruction recordings highdensity microelectrode arrays j neural eng 2022 mar 2 doi 101088 17412552 ac59a2 online ahead printabstractobjective neurons communicate sending action potentials axons velocity axonal signal propagation describes fast electrical action potentials can travel velocity can affected human brain several pathologies including multiple sclerosis traumatic brain injury channelopathies highdensity microelectrode arrays hdmeas provide unprecedented spatiotemporal resolution extracellularly record neural electrical activity high density recording electrodes enables image activity individual neurons subcellular resolution includes propagation axonal signals however axon reconstruction date mainly relies manual approaches select electrodes channels seemingly record signals along specific axon automated approach track multiple axonal branches extracellular actionpotential recordings still missingapproach article propose fully automated approach reconstruct axons extracellular electricalpotential landscapes socalled electrical footprints neurons initial electrode channel selection proposed method first constructs graph based voltage signal amplitudes latencies graph interrogated extract possible axonal branches finally axonal branches pruned axonal actionpotential propagation velocities computedmain results first validate method using simulated data detailed reconstructions neurons showing approach capable accurately reconstructing axonal branches apply reconstruction algorithm experimental recordings hdmeas show can used determine axonal morphologies signalpropagation velocities high throughputsignificance introduce fully automated method reconstruct axonal branches estimate axonal actionpotential propagation velocities using hdmea recordings method yields highly reliable reproducible velocity estimations constitute important electrophysiological feature neuronal preparationspmid35234667 doi101088 17412552 ac59a2,0.0
population pharmacokineticb cell modeling ofatumumab patients relapsing multiple sclerosis cns drugs 2022 mar 1 doi 101007 s4026302100895w online ahead printabstractbackground ofatumumab fully human anticd20 monoclonal antibody indicated treatment relapsing forms multiple sclerosis rms binds unique conformational epitope thereby depleting b cells efficiently allowing subcutaneous administration lower dosesobjectives aims characterize relationship ofatumumab concentration b cell levels including effect covariates body weight age baseline b cell count use simulations confirm chosen therapeutic dosemethods graphical regression analyses previously performed based data doserange finding study provided b cell depletion target used present work available adult phase 2 3 data ofatumumab rms patients pooled develop population pharmacokinetics pk b cell count model using nonlinear mixedeffects modeling population pkb cell model used simulate b cell depletion repletion times effect covariates pk b cell metrics well dose response across range subcutaneous ofatumumab monthly dosesresults final pkb cell model developed using data 1486 patients predetermined b cell target best achieved sustained 20mg dose regimen median b cell count reaching 8 cells l 11 days negligible repletion doses weight significant effect pk translate clinically relevant effect b cell levelsconclusion pkb cell modeling confirms dose chosen licensed ofatumumab regimen demonstrates requirement dose adjustment based adult patient characteristicspmid35233753 doi101007 s4026302100895w,0.0
norisoboldine induces development treg cells promoting fatty acid oxidationmediated h3k27 acetylation foxp3 abstractnorisoboldine alkaloid isolated radix lindera previously reported promote differentiation regulatory t cells treg cells important subtype lymphocytes capable controlling autoimmune diseases present study performed explore mechanism view cellular metabolism global metabolomic analysis indicated preferentially altered fatty acid oxidation fao pathway elevated content related metabolites treg cell differentiation detection oxygen consumption rate ocr mrna expression faorelated enzymes demonstrated promoted fao early stage treg cell differentiation consistently pharmacological genetic inhibition fao markedly diminished induction treg cell differentiation furthermore shown elevate level acetylcoa derived fao acetylation lysine 27 histone 3 h3k27 foxp3 promoter cns2 regions knockdown cpt1 ratelimiting enzyme fao weakened promotion development acetylcoa level acetylation h3k27 treg cells vitro mice collageninduced arthritis attenuated antiarthritic effect findings demonstrate induces development treg cells promoting fao therefore facilitating gene transcription foxp3 via acetylcoamediated h3k27 acetylation modification fao might serve novel target induce treg cell development,0.0
daam2 regulates myelin structure oligodendrocyte actin cytoskeleton rac1 gelsolin myelin essential neuronal health cns function oligodendrocytes ols undergo complex process cytoskeletal remodeling form compact myelin sheaths previously discovered formin protein daam2 suppresses ol differentiation wnt signaling however role cytoskeletal control remains unknown investigate used olspecific daam2 deletion daam2 cko mice either sex found myelin decompaction active period myelination postnatal development motor coordination deficits adulthood using primary ol cultures found daam2depleted ols showed morphological dysregulation differentiation suggesting daam2 regulates ol cytoskeleton vivo screening identified actin regulators rac1 gelsolin possible effectors daam2deficient ol cytoskeletal regulation using gain lossoffunction experiments primary ols found rac1 gelsolin operate downstream daam2 ol differentiation gelsolin daam2 promoting inhibiting membrane spreading late differentiation respectively vivo experiments using daam2 cko mice revealed increased protein levels gelsolin developing white matter change rna levels suggesting daam2 acts posttranslational manner suppress gelsolin levels vitro biochemical studies show daam2 induces gelsolin ubiquitination degradation ols together studies show daam2 essential formation functional myelin modulation gelsolin levels regulate ol cytoskeleton findings demonstrate critical role cytoskeletal dynamics myelination reveal novel avenues treatment variety white matter diseasessignificance statementproper myelin formation essential cns function oligodendrocytes ols require extensive changes actin cytoskeleton form myelin sheaths show formin protein daam2 necessary myelin compaction development motor learning adulthood demonstrate daam2 regulates ol differentiation morphology actin regulators rac1 gelsolin lastly find daam2 may control myelin compaction modulating ubiquitination degradation gelsolin recruitment e3 ubiquitin ligase nedd4 findings reveal novel pathways regulating myelin structure function white matter development,1.0
prevalence healthy aging among community dwelling adults age 70 older five european countries background compare prevalence healthy aging among adults age 70 older 5 european countries recruited dohealth clinical trial participants selected absence prior major health eventsmethodscrosssectional analysis dohealth baseline data 2 157 participants mean age 749 sd 44 617 women included 2 123 data domains healthy aging status ha definition ha assessed based nurses health study nhs definition requiring four domains major chronic diseases disabilities cognitive impairment montreal cognitive assessment moca 25 mental health limitation gds5 2 diagnosis depression association ha age bmi gender physical function sittostand gait speed grip strength assessed multivariate logistic regression analyses adjusting centerresultsoverall 418 dohealth participants healthy agers significant variability country austria innsbruck 583 switzerland zurich basel geneva 512 germany berlin 376 france toulouse 367 portugal coimbra 88 p 00001 differences prevalence country persisted adjustment age multivariate model younger age 095 95 ci 093 098 female gender 136 95 ci 103 181 lower bmi 094 95 ci 091 096 faster gait speed 470 95 ci 268 825 faster performance sittostand test 090 95 ci 087 093 independently significantly associated haconclusionsdespite inclusion exclusion criteria preselecting relatively healthy adults age 70 years older ha prevalence dohealth varied significantly countries highest participants austria switzerland lowest participants portugal independent country younger age female gender lower bmi better physical function associated hatrial registrationdohealth registered protocol nct01745263 international trials registry clinicaltrialsgov protocol number 201200124941 registration european community clinical trial system eudract,0.0
addressing need patientfriendly medical communications adaptation 2019 recommendations management mps vi mps iva background patients important stakeholders care disease educational need learn condition treatment receive considering need patientfocused materials present directed approach mucopolysaccharidosis mps vi mps iva pair rare inherited diseases affects multiple organs parts body independent guidelines treatment diseases recently published providing evidence expertisedriven recommendations optimize patient management however healthcare providers may training knowledge understand guidelines patients caregivers can find technical content challenging hence aimed develop plain language summaries pls mps vi mps iva guidelines patients primary audienceresultsa review guidelines expert team identified six domains information relevant patients multidisciplinary team regular tests checkups diseasemodifying supportive treatments general anesthetics earnosethroat respiratory care surgeries information adapted series infographics specific either mps vi mps iva designed appeal patients clearly present information concise mannerconclusionsthe use patientfriendly materials like infographics developed potential better inform patients engage care issue call arms medical community development similar pls materials rare diseases intended inform empower patients,0.0
evaluating impact understanding multiple sclerosis online course participant ms knowledge health literacy resilience selfefficacy quality life ms symptom severity abstractbackgroundlittle known impact online health education multiple sclerosis ms related knowledge health outcomes ms communityobjectivesto estimate impact participating massive open online course mooc ms course completer msrelated knowledge health literacy hl selfefficacy resilience quality life ms symptom severitymethodsin cohort study using single group pretest posttest design n560 examined effects mooc participation msrelated knowledge outcomes using paired ttest used regression structural equation modelling examine association participant characteristics changes outcomes changes msrelated knowledgeresultswe found significant increases msrelated knowledge people living ms pwms +213 points p0001 without ms +516 points p0001 larger effect sizes higher educational levels among pwms also significant increases seven hl subscales selfefficacy increase resilience ms symptoms severity quality life among people without ms increases two hl subscales quality life increase resilience selfefficacy changes msrelated knowledge associated sex changes study outcomesconclusionsthere significant increase msrelated knowledge unrelated changes study outcomes pwms living ms outcomespecific health educational interventions may needed affect change health outcomes,0.0
perceptions physical activity sedentary behaviour guidelines among endusers stakeholders systematic review background many worlds population across age groups abilities meeting even aware internationally recommended physical activity pa sedentary behaviour sb guidelines order enhance awareness uptake guidelines perceived positively targeted users purpose study review literature enduser stakeholder perceptions pa sb guidelinesmethodsthe electronic databases apa psycinfo cinahl medline sportdiscus using ebscohost research platform web science searched inception june 2021 keyword synonyms perceptions pa guidelines sb guidelines studies design collected stakeholder enduser responses pa sb guideline included assessed risk bias pa sb guideline type official form eg national documents organizational guidelines expert consensus statements etc country targets individuals regional provincial statewide national international level includes types guidelines eg strength aerobic clinical nonclinical screentime sitting etc data extracted analyzed using thematic synthesisresultsafter screening 1399 abstracts applying citation screening 304 fulltexts retrieved total 31 articles met inclusion criteria endusers stakeholders pa guidelines across age groups expressed need simplified language definitions relatable examples imagery quantification pa behaviours concern early years child pa guidelines leading guilt amongst parents sb guidelines particularly recommendations limit screentime unrealistic general age group pa guidelines perceived usable populations differing abilities clinical conditions socioeconomic status guidelines targeted clinical populations persons multiple sclerosis persons spinal cord injury well receivedconclusionsthere clear need balance evidence base pragmatic needs translation uptake guidelines ignored act barrier actual engagement,0.0
risk factors associated shortterm adverse events sarscov2 vaccination patients immunemediated inflammatory diseases background studies suggested incremental shortterm adverse events ae repeated vaccination report assessed occurrence risk factors shortterm aes following repeated sarscov2 vaccination patients various immunemediated inflammatory diseases imids methodsselfreported daily questionnaires aes first 7 days vaccination obtained 2259 individuals 2081 patients 178 controls participating ongoing prospective multicenter cohort study sarscov2 vaccination patients various imids netherlands t2bcovid relative risks calculated potential risk factors associated clinically relevant ae rae defined ae lasting longer 2 days impacting daily liferesultsin total 5454 vaccinations recorded 1737 first 1992 second 1478 third vaccinations multiple sclerosis crohns disease rheumatoid arthritis largest disease groups raes reported 573 95 ci 548598 patients first vaccination 615 95 ci 592637 second vaccination 58 95 ci 553606 third vaccination day 7 first second third vaccination respectively 76 95 ci 6391 74 95 ci 6287 68 95 ci 5483 patients still reported aes impacting daily life hospital admissions allergic reactions uncommon 07 female sex arr 143 95 ci 132156 age 50 arr 114 95 ci 106123 preceding sarscov2 infection arr 114 95 ci 101129 imid arr 116 95 ci 101134 associated increased risk raes following vaccination compared second vaccination first vaccination associated lower risk raes arr 092 95 ci 084099 third vaccination associated increased risk raes arr 093 95 ci 084102 bnt162b2 vaccines associated lower risk raes compared cx024414 arr 086 95 ci 080093 conclusionsa third sarscov2 vaccination associated increased risk raes imid patients compared second vaccination patients imid modestly increased risk raes vaccination compared controls aes resolved within 7 days hospital admissions allergic reactions uncommontrial registrationnl7497401820 trial id nl8900 registered 9 september 2020,0.0
rehabilitative interventions ischaemic digital ulcers pain hand functioning systemic sclerosis prospective beforeafter study background systemic sclerosis ssc rare connective tissue disease characterised immune dysfunction vasculopathy cellular inflammation fibrosis skin associated multiple internal organs involvement ischaemic digital ulcers idu hands commonly occur patients ssc adversely affecting functional independencepurposeaim study investigate effectiveness rehabilitation protocol based combined use ultrasound us therapy therapeutic exercise terms ulcers healing pain relief hand functioning patients affected ssc idus moreover also investigated safety proposed interventionstudy designprospective beforeafter studymethodswe included 20 patients idus secondary ssc patients treated us combined manual therapy including mcmennel joint manipulation pompage mobilization technique connective tissue massage 10 sessions evaluated softness dyschromia pain hand mobility using pressure sore status tool psst numerical rating scale nrs duruoz hand index dhi t0 end treatment t1 resultstreatment us combined manual therapy significantly reduced ulcers depth improved ulcers margins reduced periwound skin damage median psst score 16 t1 p00001 moreover significant benefits reported terms pain relief nrs 3 t1 p00005 hand function dhi score 19 t1 p00005 finally approach seems safe without side effects reported end treatment along optimal complianceconclusiontherapeutic us combined manual therapy used additional intervention manage idus ssc patients,0.0
treatment regimens neuromyelitis optica spectrum disorder attacks retrospective cohort study background neuromyelitis optica spectrum disorder nmosd attacks require urgent probabilistic antiinflammatory therapeutic strategy inadequately treated attacks result disability need identify optimal attacktreatment regimen study aimed identify predictors outcome first attack patients nmosd presentation propose best treatment strategymethodswe performed retrospective cohort study french national nmosd registry nomadmus nested cohort french multiple sclerosis observatory ofsep recruiting patients nmosd presentations france studied first attack independent locations clinical core characteristic nmosd treatmentnave patients primary outcome evolution expanded disability status scale edss score 6 months stratified two ways account recovery return baseline edss score treatment response classified good edss score decreased 1 point nadir edss score 3 2 points nadir edss score 3 used ordinal logistic regression infer statistical associations outcomeresultswe included 211 attacks among 183 patients 104 antiaqp4 antibodies 60 antimog antibodies 19 double seronegative attack treatment regimens comprised corticosteroids n 196 plasma exchanges pe n 72 intravenous immunoglobulins n 6 complete recovery reached 40 attacks 19 6 months treatment response good 134 attacks 635 improvement edss score 50 attacks 237 mogantibody seropositivity short delays pe significantly independently associated better recovery treatment responseconclusionswe identified two prognostic factors serostatus better outcomes among mogabpositive patients delay pe therefore argue aggressive antiinflammatory management first attacks suggesting nmosd presentation early combination pe corticosteroids,0.0
seroconversion covid19 vaccination multiple sclerosis patients high efficacy disease modifying medications abstractthe impaired ability mount effective immune response vaccination leaves immunosuppressed patients higher risk severe covid19 infection retrospective study aimed evaluate covid19 seroconversion antibody titers patients immune modulating therapies compared disease modifying therapy dmt expected individuals bcell depletion therapies bcdt sphingosine 1phosphate s1p modulators impaired humoral response mrna vaccination observed variable seroconversion depending type bcell depleting medication smaller percentage seroconversion patients infused bcdt ibcdt ocrelizumab rituximab compared ofatumumab humoral response vaccination impaired individuals natalizumab untreated ms patients observations may influence dmt selection covid19 era,0.0
central nervous system regeneration roles glial cells potential molecular mechanism underlying remyelination abstractglial cells play crucial roles brain homeostasis pathogenesis central nervous system cns injuries diseases however roles cells molecular mechanisms toward regeneration cns fully understood especially capacity toward demyelinating diseases therefore still limited therapeutic strategies restore function adult cns diseases multiple sclerosis ms remyelination spontaneous regeneration process cns requires involvement multiple cellular extracellular components promoting remyelination therapeutic interventions promising novel approach restore cns function herein review role glial cells cns diseases injuries particularly discuss roles glia functional interactions regulatory mechanisms remyelination well current therapeutic strategies ms,1.0
expert opinion recognition diagnosis management children adults fabry disease multidisciplinary turkey perspective abstractthis consensus statement panel fabry experts aimed identify areas consensus conceptual clinical therapeutic aspects fabry disease fd provide guidance healthcare providers best practice management pediatric adult patients fd consensus statement indicated clinical heterogeneity fd well large number pathogenic variants gla gene emphasizing need individualized approach patient care experts reached consensus critical role high index suspicion symptomatic patients screening certain atrisk groups reveal timely accurate diagnosis fd along increased awareness treating physician different kinds pathogenic variants clinical implications experts emphasized crucial role timely recognition fd minimal delay symptom onset definite diagnosis better management fd patients given likelihood changing diseases natural history improving patients quality life prognosis enzyme replacement therapy ert administered coordinated multidisciplinary care approach regard consensus document expected increase awareness among physicians unique characteristics fd assist clinicians recognizing fd wellestablished clinical suspicion consistent pathogenic variants genderbased heterogeneous clinical manifestations fd translating information clinical practice best practice management patients fd,0.0
peptidylarginine deiminase 2 promotes t helper 17like t cell activation activated t cellautonomous death acad endoplasmic reticulum stress autophagy coupling mechanism abstractpeptididylarginine deiminase type 2 padi2 catalyzes conversion arginine residues citrulline residues proteins demonstrate padi2 induces t cell activation investigate padi2 promotes activated t cell autonomous death acad activated jurkat t cells overexpression padi2 significantly increases citrullinated proteins induces endoplasmic reticulum er stress unfolded protein response upr signaling ultimately resulting expression autophagyrelated proteins autophagy padi2 promoted autophagy resulted early degradation p62 light chain 3b lc3b ii accumulation jurkat t cells silencing autophagyrelated gene atg 12 protein inhibits padi2mediated autophagy promotes er stress apoptosis whereas overexpression atg12 decreased er stress prolonged autophagy promote cell survival additionally padi2 regulates t cell activation production th17 cytokines jurkat t cells interleukins 6 il17a il17f il21 il22 jurkat t cells silencing il6 promotes autophagy mediated padi2 inhibits padi2induced apoptosis whereas silencing beclin1 increases activation survival th17like t cells decreasing autophagy apoptosis padi2 silencing alleviates er stress caused padi2 decreases cytokine expression associated th17like t cell activation acad propose padi2 involved th17 lymphocyte acad via mechanism involving er stress autophagy tightly regulated padi2mediated citrullination findings suggest inhibiting th17 t cell activation development severe autoimmune diseases may possible use novel antagonists specifically target padi2,0.0
guidelines bioinformatics singlecell sequencing data analysis alzheimers disease review recommendation implementation application abstractalzheimers disease ad common form dementia characterized progressive cognitive impairment neurodegeneration extensive clinical genomic studies revealed biomarkers risk factors pathways targets ad past decade however exact molecular basis ad development progression remains elusive emerging singlecell sequencing technology can potentially provide celllevel insights disease systematically review stateoftheart bioinformatics approaches analyze singlecell sequencing data applications ad 14 major directions including 1 quality control normalization 2 dimension reduction feature extraction 3 cell clustering analysis 4 cell type inference annotation 5 differential expression 6 trajectory inference 7 copy number variation analysis 8 integration singlecell multiomics 9 epigenomic analysis 10 gene network inference 11 prioritization cell subpopulations 12 integrative analysis human mouse scrnaseq data 13 spatial transcriptomics 14 comparison single cell ad mouse model studies single cell human ad studies also address challenges using human postmortem mouse tissues outline future developments single cell sequencing data analysis importantly implemented recommended workflow major analytic direction applied large single nucleus rnasequencing snrnaseq dataset ad key analytic results reported scripts data shared research community github summary comprehensive review provides insights various approaches analyze single cell sequencing data offers specific guidelines study design variety analytic directions review accompanied software tools will serve valuable resource studying cellular molecular mechanisms ad diseases biological systems single cell level,0.0
role nk nkt cells pathogenesis improvement multiple sclerosis following diseasemodifying therapies health sci rep 2022 jan 24 5 1 e489 doi 101002 hsr2489 ecollection 2022 janabstractbackground multiple sclerosis ms autoimmune inflammatory disease central nervous system cns t cells become autoreactive recognizing cns antigens innate adaptive immune systems involved pathogenesis ms recent years impact innate immune cells ms pathogenesis received attention cd56bright nk cells immunoregulatory subset nk cells can increase production cytokines modulate adaptive immune responses whereas cd56dim nk cells active cytolysis functions two main subsets nk cells may different effects onset progression ms invariant nkt inkt cells immune cells involved control autoimmune diseases however variant nkt vnkt cells despite limited information play role ms remission via immunoregulatory pathwayaim aimed evaluate influence ms therapeutic agents nk nkt cells nk cell subtypesmaterials methods possible mechanism ms therapeutic agent presented focusing effects different diseasemodifying therapies number nk nkt subtypesresults expansion cd56bright nk cells reduction cd56dim cells enhancement nkt cells important innate immune cells alterations following diseasemodifying therapiesconclusion expansion cd56bright nk cells reduction cd56dim cells associated successful response different treatments ms inkt vnkt cells beneficial effects ms improving seems enhanced due ms drugs leading disease improvement however reduction number nkt cells due adverse effects ms drugs bone marrowpmid35229046 pmcpmc8865072 doi101002 hsr2489,0.0
partners crime proteins implicated rna repeat expansion diseases wiley interdiscip rev rna 2022 feb 28e1709 doi 101002 wrna1709 online ahead printabstractshort tandem repeats repetitive nucleotide sequences robustly distributed human genome expansion underlies pathogenesis multiple neurological disorders including huntingtons disease amyotrophic lateral sclerosis frontotemporal dementia fragile xassociated tremor ataxia syndrome myotonic dystrophies known repeat expansion disorders reds several molecular pathomechanisms associated toxic rna containing expanded repeats rnaexp shared among reds contribute disease progression however detailed mechanistic insight processes limited deepen understanding interplay toxic rnaexp molecules multiple protein partners review discuss roles selected rnabinding proteins rbps interact rnaexp thus act partners crime progression reds gather current findings concerning rbps involved different stages rnaexp life cycle transcription splicing transport augindependent translation expanded repeats argue activity selected rbps can unique common among reds depending expanded repeat type also present proteins functionally depleted due sequestration rnaexp within nuclear foci participate rnaexp dependent innate immunity activation moreover discuss utility selected rbps targets development therapeutic strategies article categorized rna interactions proteins molecules proteinrna interactions functional implications rna disease development rna diseasepmid35229468 doi101002 wrna1709,0.0
transition secondary progressive multiple sclerosis consequences patients healthcare systems healthcare professional survey health sci rep 2022 jan 23 5 1 e474 doi 101002 hsr2474 ecollection 2022 janabstractbackground aims transition secondary progressive multiple sclerosis spms relapsingremitting ms rrms expected part disease trajectory patients however transition challenging identify due gradual nature progression complications superimposed relapses comorbidities natural variability symptoms healthcare professional hcp survey sought characterize transition management spms uk clinical practicemethods telephone interviews 20 neurologists ms specialist nurses england scotland gathered quantitative qualitative responses numerical analyses theoretical thematic methods used identify key emerging themesresults burden spms imposes patients caregivers major theme discharge specialist services common leading sense abandonment respondents acknowledged substantial hesitancy toward identifying spms predominantly due restricted options licensed reimbursed diseasemodifying therapies dmts spms compared rrms currently hcps continue dmts label rrms even recognition progression survey identified ms unusual comparison disease areas reimbursement guidelines direct impact clinicians decisions around disease staging respondents suggested reimbursed dmts proven slow disability progression spms will create stepchange identifying spms providing rationale acknowledge progression earlier removing key obstacles identification aid change respondents identified need spmsspecific diagnostic guidance despite substantial divergence implementation current guidanceconclusions contrast current heterogeneity structured standardized approach identification spms along guidelines treatment will ensure patients can maximally benefit treatment options spms evolvepmid35229042 pmcpmc8865068 doi101002 hsr2474,0.0
incentivizing prescription drug switching reduce patient health plan spending microsimulation model value health 2022 mar 25 3 427434 doi 101016 jjval202108012 epub 2021 oct 1abstractobjectives spending prescription drugs branded drugs direct generic equivalents many drugs therapeutic alternatives within class estimate potential savings providing patients financial incentive switch higher cost drug lower cost therapeutic alternative drugmethods used individual statetransition microsimulations model medication use spending without financial incentives 12month time horizon healthcare sector perspective costs utilization inputs individuals branded insulins multiple sclerosis drugs enrolled regional mixedmodel health maintenance organization basecase model used onetime financial incentive 83 250 offered patients higher cost insulin multiple sclerosis treatments respectively switch lower cost drugs within classresults savings per individual offered incentive insulin multiple sclerosis classes respectively 84 95 ci 46122 2 127 95 ci 2673 987 varying incentive size switch probability resulted maximum savings 712 elasticity 02 incentive size 250 insulin drug class multiple sclerosis drug class maximum savings 5945 elasticity 02 incentive size 1000 short time horizon makes savings estimates conservativeconclusions programs financial incentives encourage even small proportion patients switch among drugs within therapeutic class substantial savings generatedpmid35227455 doi101016 jjval202108012,0.0
safety experience continued exposure ofatumumab patients relapsing forms multiple sclerosis 35 years mult scler 2022 mar 113524585221079731 doi 101177 13524585221079731 online ahead printabstractbackground ofatumumab approved treatment relapsing multiple sclerosis rms ongoing safety reporting crucial understand longterm benefitrisk profileobjective report safety tolerability ofatumumab rms extended treatment 35 yearsmethods patients completing asclepios ii phase 3 aplios apolitos phase 2 trials enter alithios phase 3b openlabel longterm safety study analyzed cumulative data continuous ofatumumab treatment patients newly switched teriflunomideresults safety population 1969 patients 1292 continuously treated ofatumumab median timeatrisk 355 months 3253 patientyears 677 newly switched median timeatrisk 183 months 986 patientyears total 1650 patients 838 1 adverse events 191 97 1 serious adverse events opportunistic infections progressive multifocal leukoencephalopathy events identified risk malignancies low mean serum immunoglobulin ig g levels remained stable mean igm levels decreased remained lower limit normal serious infection incidence low decreased ig levels associated serious infectionsconclusion patients 35 years exposure ofatumumab well tolerated new safety risks identified findings established effectiveness support favorable benefitrisk profile ofatumumab rmspmid35229668 doi101177 13524585221079731,0.0
role cerebellar damage explaining disability cognition multiple sclerosis phenotypes multiparametric mri study j neurol 2022 mar 1 doi 101007 s00415022110211 online ahead printabstractbackground cerebellar involvement comprehensively studied mri point view multiple sclerosis ms aimed quantify cerebellar damage identify predictors physical disability cognitive dysfunction ms patients characterize patients cerebellar disabilitymethods prospective study 164 89 relapsingremitting 75 progressive ms patients 53 healthy controls enrolled subjects underwent 3t mri sequences assessing lesions atrophy cerebellum supratentorial brain brainstem cervical cord cerebellar peduncle diffusiontensor metrics also derived random forest models identified mri predictors expanded disability status scale edss score cognition zscore hierarchical clustering applied mri metrics patients cerebellar disabilityresults ms patients predictors higher edss score outofbagr2 083 lower cord grey matter gm global areas brain volume gm volume gmv cortical gmv cerebellum lobules iiv vermis gmv higher cord gm brainstem lesion volume lv predictors lower cognition zscore outofbagr2 025 higher supratentorial superior cerebellar peduncle lv lower brain thalamus basal ganglia volumes gmv cerebellum lobule viiib crus ii gmv patients cerebellar disability found three clusters homogenous mri metrics patients high brain lesion volumes including cerebellar peduncles marked cerebellum gm atrophy patients severe cord damageconclusions damage cerebellum gm connecting structures relevant role explaining cognitive dysfunction physical disability ms datadriven mri clustering might improve knowledge mriclinical correlationspmid35230471 doi101007 s00415022110211,0.0
development ageadjusted model blood neurofilament light chain ann clin transl neurol 2022 mar 1 doi 101002 acn351524 online ahead printabstractobjective develop ageadjustment model neurofilament light chain nfl emerging injury marker patients range neurologic conditions including multiple sclerosis ms methods serum plasma samples collected healthy donor hd cohort 118 individuals aged 24 66 years 90 patients relapsing ms rms 22 patients progressive ms pms serum plasma samples assessed nfl using simoa assay quanterix nfl advantage kit loglinear model used evaluate relationship nfl age calculate ageadjusted nfl levelsresults higher serum plasma nfl levels significantly associated increasing hd age logtransformation blood nfl levels reduced heteroscedasticity skewness loglinear model enabled adjustment agerelated increase serum plasma nfl levels 23 95 ci 1629 26 95 ci 1333 per year respectively following age adjustment nfl show significant association hd sex ethnicity unadjusted serum nfl levels elevated patients pms mean age 56 years compared rms mean age 37 years ageadjusted nfl levels differinterpretation loglinear age adjustment model developed enable comparison nfl levels across populations different ages additional data evidence needed patientlevel adoption valuable tool interpreting nfl levels across range patient groups neurologic conditionspmid35229997 doi101002 acn351524,0.0
case sporadic amyotrophic lateral sclerosis als senataxin setx gene variant rinsho shinkeigaku 2022 feb 25 doi 105692 clinicalneurolcn001675 online ahead printabstracta 67yearold man presented slowly progressive weakness extremities visited hospital nerve conduction study showed axonal neuropathy needle electromyography showed neurogenic changes denervation findings multiple limb muscles diagnosed probable amyotrophic lateral sclerosis als defined awaji criteria diagnosis als develop either respiratory muscle paralysis bulbar palsy characteristic symptoms sporadic als genetic testing revealed novel gene variant senataxin setx causative gene als4 make definite diagnosis als4 relatives perform genetic testing segregation study however considered variant can pathogenic previously reported absent least 1 000 healthy control individuals variant site highly conserved mammals may impair function senataxin protein silico analysis pmid35228463 doi105692 clinicalneurolcn001675,0.0
impact antipdgfr antibody surface functionalization lnc uptake oligodendrocyte progenitor cells int j pharm 2022 feb 26121623 doi 101016 jijpharm2022121623 online ahead printabstractimpairment oligodendrocyte progenitor cell opc differentiation oligodendrocytes chronic inflammation key determinants poor remyelination observed diseases multiple sclerosis many promyelinating molecules therapeutic potential hindered poor solubility limited access targeted cells promising approach improve delivery molecules opc encapsulate functionalized lipid nanocapsules lnc aimed develop first opctargeting lnc grafting antipdgfr antibody surface lnc using several strategies evaluating interaction pdgfr via elisa found siteselective clickchemistry grafting maintained antipdgfr pdgfr association confirmed vitro primary rat opc conclusion demonstrated possible produce antipdgfr functionalized lnc confirmed antibodys ability recognize receptor grafting optimized techniques characterize antibody functionalized lncpmid35231547 doi101016 jijpharm2022121623,1.0
pulmonary langerhans cell histiocystosis plch lymphangioleiomyomatosis lam circulating cells loss heterozygosity tsc2 gene chest 2022 feb 26s00123692 22 003981 doi 101016 jchest202202032 online ahead printabstractbackground lymphangioleiomyomatosis lam pulmonary langerhans cell histiocytosis plch cystic lung diseases neoplastic cell believed responsible disease pathogenesis neoplastic lam cell mutations tuberous sclerosis complex tsc genes tsc1 tsc2 whereas neoplastic plch cell may mutations several genes eg braf nras map2k1 mutations specific plch described multiple cancers tsc1 tsc2 mutations loss heterozygosity loh also described cancersresearch question tsc2 loh specific lam also found plch toostudy design recruited lam patients 53 healthy volunteers 22 compared presence cells tsc2 loh plch patients 12 blood urine samples collected analysismethods fluorescenceactivated cell sorting facs used identify subpopulations cells blood urine samples isolated cd45cd235a cd45cd235a+ cd45+cd235a cells blood following density gradient separation cells screened tsc2 loh 5 microsatellites markers ie kg8 d16s3395 d16s3024 d16s521 d16s291 obtained four cell subpopulations urine ie cd44v6+cd9+ cd44v6+cd9 cd44v6cd9+ cd44v6cd9 results using facs cells isolated blood urine plch patients showed tsc2 loh healthy volunteers cells tsc2 loh control cells isolated blood urine lam patients gave results similar reported previously data show tsc2 loh found patients cystic lung diseases potential neoplastic characteristics well patients cancerinterpretation presence tsc2 loh circulating cells specific lam data suggest chromosomal abnormalities affecting tsc2 gene found diseases associated cells cancerlike neoplastic cellspmid35231481 doi101016 jchest202202032,0.0
phosphoproteome profiling receptor tyrosine kinase musk identifies tyrosine phosphorylation rab gtpases mol cell proteomics 2022 feb 25100221 doi 101016 jmcpro2022100221 online ahead printabstractmusclespecific receptor tyrosine kinase musk agonist antibodies developed two decades ago explore benefits receptor activation neuromuscular junction unlike agrin endogenous agonist musk agonist antibodies function independently coreceptor lrp4 delay onset muscle denervation mouse models amyotrophic lateral sclerosis als performed dose response time course experiments myotubes systematically compare sitespecific phosphorylation downstream agonist remarkably agonists elicited similar intracellular responses known newly identified musk signaling components among inducible tyrosine phosphorylation multiple rab gtpases blocked musk kinase inhibition importantly mutation site rab10 disrupts association adaptor molecules mical1 3 together data provide indepth characterization musk signaling describe two novel musk inhibitors expose phosphorylation rab gtpases downstream receptor tyrosine kinase activation myotubespmid35227894 doi101016 jmcpro2022100221,0.0
resolving inflammatory links myocardial infarction vascular dementia semin immunol 2022 feb 25101600 doi 101016 jsmim2022101600 online ahead printabstractmyocardial infarction associated increased risk vascular dementia myocardial infarction vascular dementia evidence elevated inflammatory biomarkers associated worsened clinical outcomes myocardial infarction leads systemic inflammatory response may contribute recruitment activation myeloid cells including monocytes microglia perivascular macrophages within central nervous system however understanding causative roles cells linking cardiac injury development progression dementia incomplete herein provide overview inflammatory cellular molecular links myocardial infarction vascular dementia discuss strategies resolve inflammation myocardial infarction limit neurovascular injurypmid35227567 doi101016 jsmim2022101600,0.0
sphingomyelin maintains cutaneous barrier via regulation stat3 pathway abstractepidermal tissues play vital roles maintaining homeostasis preventing dysregulation cutaneous barrier sphingomyelin sm sphingolipid synthesized sphingomyelin synthase sms 1 2 involved signal transduction via modulation lipidraft functions though implications sms inflammatory diseases reported role dermatitis clarified study investigated role sm cutaneous barrier using dermatitis model established employing sgms1 2 deficient mice sm deficiency impaired cutaneous inflammation upregulated signal transducer activator transcription 3 stat3 phosphorylation epithelial tissues furthermore using mouse embryonic fibroblast cells sensitivity stat3 interleukin6 stimulation increased sgmsdeficient cells using tofacitinib clinical jak inhibitor study showed sm deficiency might participate stat3 phosphorylation via jak activation overall results demonstrate sm essential maintaining cutaneous barrier via stat3 pathway suggesting sm potential therapeutic target dermatitis treatment,1.0
incremental burden relapse patients major depressive disorder realworld retrospective cohort study using claims data background relapse common major depressive disorder mdd study evaluated incremental health care burden relapse patients mddmethodsthis realworld retrospective cohort study used administrative medical pharmacy claims data identify commercially insured adult patients united states diagnosed mdd initiated new antidepressant january 1 2012 september 30 2017 allcause health care resource utilization total costs medication adherence evaluated two cohorts patients patients without relapse relapse defined suicide attempts psychiatric hospitalization mental healthrelated emergency department ed visit use electroconvulsive therapy reinitiation treatment gap 6 monthsresultsthe study population included 14 186 patients 7093 baselinematched patients per cohort mean followup period 275 260 months patients patients without relapse respectively patients relapse significantly higher rates hospitalization 166 vs 85 p 0001 ed visits 548 vs 347 p 0001 patients without relapse total costs patients relapse significantly higher 12 594 vs 10 445 p 0001 patients relapse also less adherent antidepressants mean proportion days covered 043 vs 049 p 0001 conclusionsrelapse mdd associated increased total costs health care utilization lower adherence antidepressants reducing risk relapse may result reduction associated health care burden however findings may generalizable patients commercial insurance,0.0
serum neurofilament light chain individual prognostication disease activity people multiple sclerosis retrospective modelling validation study summarybackgroundserum neurofilament light chain snfl biomarker neuronal damage used monitor disease activity response drugs prognosticate disease course people multiple sclerosis group level absence representative reference values correct physiological agedependent increases snfl limited diagnostic use biomarker individual level aimed assess applicability snfl identification people risk future disease activity establishing reference database derive reference values corrected age bodymass index bmi furthermore used reference database test suitability snfl endpoint grouplevel comparison effectiveness across diseasemodifying therapiesmethodsfor derivation reference database snfl values control group created comprising participants evidence cns disease taking part four cohort studies europe north america modelled distribution snfl concentrations function physiological agerelated increase bmidependent modulation derive percentile z score values reference database via generalised additive model location scale shape tested reference database participants multiple sclerosis swiss multiple sclerosis cohort smsc compared association snfl z scores clinical mri characteristics recorded longitudinally ascertain respective disease prognostic capacity validated findings independent sample individuals multiple sclerosis followed swedish multiple sclerosis registryfindingswe obtained 10 133 blood samples 5390 people median samples per patient 1 iqr 12 control group control group snfl concentrations rose exponentially age steeper increased rate approximately 50 years age obtained 7769 samples 1313 people median samples per person 60 iqr 3080 people multiple sclerosis smsc snfl percentiles z scores indicated gradually increased risk future acute eg relapse lesion formation chronic disability worsening disease activity snfl z score 15 associated increased risk future clinical mri disease activity people multiple sclerosis odds ratio 315 95 ci 235423 p00001 people considered stable evidence disease activity 266 108655 p0034 increased z scores outperformed absolute raw snfl cutoff values diagnostic accuracy group level longitudinal course snfl z score values people multiple sclerosis smsc decreased seen control group use monoclonal antibodies ie alemtuzumab natalizumab ocrelizumab rituximab lesser extent oral therapies ie dimethyl fumarate fingolimod siponimod teriflunomide however longitudinal snfl z scores remained elevated platform compounds interferons glatiramer acetate p00001 interaction term treatment category treatment duration results fully supported validation cohort n4341 swedish multiple sclerosis registryinterpretationthe use snfl percentiles z scores allows identification individual people multiple sclerosis risk detrimental disease course suboptimal therapy response beyond clinical mri measures specifically people disease activityfree status additionally snfl might used endpoint comparing effectiveness across drug classes pragmatic trialsfundingswiss national science foundation progressive multiple sclerosis alliance biogen celgene novartis roche,0.0
pulmonary arterial hypertension hereditary hemorrhagic telangiectasia associated acvrl1 mutation case report abstractintroductionhereditary hemorrhagic telangiectasia autosomal dominant condition estimated prevalence 1 5000 characterized presence abnormalities vascular structures may affect many organ systems including lungs brain spinal cord gastrointestinal tract liver causative mutation identified approximately 97 patients definite hereditary hemorrhagic telangiectasia one three genes including mutation endoglin mutation locus mapped chromosome 5 activin receptorlike kinase1 acvrl1 mutation associated increased incidence primary pulmonary hypertension pulmonary arterial hypertension rare 1525 cases per million people severe vascular disorder heritable pulmonary arterial hypertension associated several gene mutations 75 mutation bone morphogenetic protein receptor 2 bmpr2 however remaining 25 patients associated genetic mutations including acvlr1 also associated hereditary hemorrhagic telangiectasia pulmonary arterial hypertension rare complication patients hereditary hemorrhagic telangiectasia 1 hereditary hemorrhagic telangiectasia population describe case report rare occurrencecase presentationa 70yearold white caucasian irish male presented screening hereditary hemorrhagic telangiectasia due history recurrent epistaxis week family history suggestive pulmonary hypertension genetic testing confirmed acvrl1 mutation echocardiogram right heart catheterization confirmed pulmonary arterial hypertension examination several mucocutaneous telangiectasia across face commenced tadalafil macitentan however led increased iron deficiency anemia pedal edema selexipag also added drug regime continues require intermittent admissions diuresis blood transfusionsconclusionthe association hereditary hemorrhagic telangiectasia pulmonary arterial hypertension rare 1 describe case hereditary hemorrhagic telangiectasia complicated pulmonary arterial hypertension result acvrl1 mutation also describe clinical challenges treating two conditions together treatment options pulmonary arterial hypertension tend worsen hereditary hemorrhagic telangiectasia symptoms,0.0
multiple sclerosis two decades progress past 20 years seen remarkable advances multiple sclerosis including better understanding fundamental immune drivers mediate cns demyelination neurodegeneration identification risk genes precise account epidemiology incidence development highly effective therapeutics nowadays multiple sclerosis relapses can completely safely eliminated patients treatmentresistant progressive symptoms can partially slowed together breakthroughs represent profound achievement modern molecular medicine,0.0
role bordetella pertussis development multiple sclerosis background multiple sclerosis ms one common neurological disorders main cause identified yet studies mentioned possible role infectious agents chlamydia pneumonia mycoplasma also b pertussis via asymptomatic nasopharyngeal colonization current study aimed investigate compared serum level b pertussis antibody rate nasopharyngeal colonization pathogen subjects without msmethodsin casecontrol study 109 patients ms 114 subjects without ms referred sina hospital hamadan 2019 studied compared terms serum titer b pertussis antibody nasopharyngeal colonization bacterium colonization evaluated using culture realtime pcr techniques data analyzed using spss version 16 95 confidence intervalresultsthe serum titer b pertussis antibody case control groups 378 351 respectively p 074 culture realtime pcr techniques revealed case nasopharyngeal colonization b pertussisconclusionthere difference b pertussis antibody titer rate nasopharyngeal colonization ms patients healthy control group therefore seems probably b pertussis role ms development,0.0
reality multiple sclerosis assessment middleincome countries position paper mike wattjes colleagues1 recommends frequent monitoring patients multiple sclerosis using mri however middleincome countries brazil reality low availability neuroimaging diagnosis monitoring patients neurological diseases outpatients might wait months cases never obtain neuroimaging public healthcare system pay private health care prices unaffordable great number people need anaesthetic sedation patients largely precludes use mri children high cost anesthesia public private healthcare systems short online survey 150 neurologists brazil asked think performing mri problem patients whether due cost reasons 19 32 60 respondents answered frequently 33 55 answered sometimes appendix p 2 finding alternatives mri diagnosis monitoring can improve care patients necessity despite low specificity low topographic resolution evoked potentials high sensitivity neural alterations particularly promising even subclinical impairments nerve conduction can disrupt wave latency wave magnitude waveforms2 3 4 however rise neuroimaging higher specificity spatial resolution evoked potentials allowed location lesions determined much accurately significantly improved diagnosis neurological disorders including multiple sclerosis2 therefore evoked potentials losing ground despite high sensitivity demyelinating diseasesneuroimaging irreplaceable obtaining specific diagnosis neurology however patients established diagnosis multiple sclerosis optic neuritis might benefit followup using evoked potentials given examinations easier cheaper mri sensitive changes functional state nervous system around 30 years rise highresolution neuroimaging evoked potentials proposed show stronger association clinical symptoms neuroimaging5 survey asked whether use evoked potentials 34 57 neurologists replied adopt exam general practice appendix p 2 therefore call new clinical techniques studies using evoked potentials hope future recommendations diagnosis monitoring people multiple sclerosis can include approach patient followupdma prg developing new technology recording analysing evoked potentials diagnosis neurological diseases authors declare competing interests,1.0
reality multiple sclerosis assessment middleincome countries authors reply great interest read correspondence response magnetic resonance imaging multiple sclerosis magnims consortium multiple sclerosis centres cmsc north american imaging multiple sclerosis cooperative naims recommendations use mri multiple sclerosis1we like thank dimitri marques abramov colleagues bringing light important issue care people multiple sclerosisthe concern limited access neuroimaging facilities particularly mri diagnosis monitoring people neurological diseases countries developing economiesthis concern certainly relevant multiple sclerosis monitoring compelling evidence brain occasionally spinal cord mri done yearly least patients receiving diseasemodifying drug monitoring treatment effectiveness prediction treatment response monitoring drug safety annual interval extended patients clinically stable first years particularly monitoring drug safety required patients mri assessment disease activity effect therapeutic managementaccording magnimscmscnaims recommendations 1 abbreviated protocol highquality threedimensional fluidattenuated inversion recovery cases gadoliniumenhanced t1weighted sequences generally sufficient monitoring purposes shortened protocol can obtained less 1520 min can implemented easily full mri protocol used diagnostic purposesalthough cost mri scan varies greatly countries generally lower developing economies developed economies contrast cost diseasemodifying drugs appears higher least latin american countries north america uk2 means cost obtaining annual mri scan monitoring purposes low compared total cost multiple sclerosis mainly dominated use diseasemodifying drugs3abramov colleagues propose consideration multimodal evoked potentials settings mri limited availability evoked potentials shown value supporting diagnosis multiple sclerosis although included 2017 mcdonald diagnostic criteria evoked potentials might also contribute predicting prognosis visual evoked potentials proposed response biomarker clinical trials particularly studies aiming promote remyelination halt multiple sclerosis progression4 evoked potentials however low accuracy terms spatial resolution pathology limited reliability incapable identifying treatmentrelated adverse events neither sensitive specific detecting focal inflammatory activity particularly outside examined systems5local programmes must established ensure availability mri monitoring patients multiple sclerosis low cost use abbreviated standardised protocols change contribute better costefficient management individuals multiple sclerosis currently possible countries developing economiesar serves scientific advisory boards novartis sanofigenzyme synthetic mr roche biogen tensormedical olea medical received speaker honoraria bayer sanofigenzyme merckserono teva pharmaceutical industries novartis roche biogen received personal fees biogen consortium ms centers sanofi genzyme bayer healtcare roche novartis teva neuroscience dsr reports personal fees bounds law group grants vertex sanofigenzyme abata therapeutics outside submitted work addition dsr patent system method automatically detecting tissue abnormalities issued us patent 9 607 392 patent method analysing multisequence mri data analysing brain abnormalities patient issued us patent 9 888 876 patent automatic identification patients risk multiple sclerosis pending us patent application 16 254 710 patent highresolution cerebrospinal fluidsuppressed t2weighted magnetic resonance imaging cortical lesions pending us patent application 62 838 578 mpw reports personal fees novartis sanofygennzyme genilac bayer heathcare roche biogen biologix celgene merck serono imcyse ixico medison,1.0
validity residuals approach measuring resilience adverse childhood experiences background resilience broadly defined ability maintain regain functioning face adversity recent work harmonise quantification definition resilience quantifies resilience residual variance psychosocial functioning remains accounting adversity exposure however published studies formally investigated validity approach considering examine construct predictive validity residuals approach using participants avon longitudinal study parents children alspac multigenerational longitudinal cohort studymethodswe regressed exposures adolescent adversity adolescent psychopathology scores using strength difficulties questionnaire obtained residual variance investigated construct validity analysing whether previously identified demographic resilience factors significantly predicted resilience predictive validity resilience investigated comparing predictive power resilience determinants psychosocial functioning two developmental outcomes depressive symptoms 18 years measured short moods feelings questionnaire neet employment education training status 17 23 years associations depressive symptoms 18 resilience aces covariates tested using multiple linear regression neet status 17 23 run separate binary multiple logistic regression models test associations resilience known demographics previously associated neet statusresultsseven previously identified protective factors including selfesteem positive sibling relationship temperament positive perception school significantly predicted resilience adolescent psychopathology thus providing strong construct validity resilience significantly predicted reduction depressive symptoms 18 years significantly decreased likelihood neet status 17 years 23 years even taking account early childhood adversity risk factors none socioeconomic factors significantly associated resilienceconclusionsour study demonstrates residuals method operationalising resilience good construct predictive validity yet recommend replication studies potential advance research mechanisms modifiability resiliencetrial registration applicable,0.0
iatrogenic calcinosis cutis 9monthold baby boy case report background calcinosis cutis rare condition characterized accumulation calcium salts skin subcutaneous tissue several types condition including dystrophic metastatic idiopathic calciphylaxis iatrogenic calcinosis cutis type related case iatrogenic calcinosis cutis one possible causes calcium intravenous infusion physicians aware condition giving calcium infusioncase presentationhere report case 9monthold arabic saudi baby boy presented abnormal movement 1 day upon investigation abnormal movement found manifestation hypocalcemia vitamin d deficiency treated intravenous calcium gluconate later treatmentrelated complication intravenous calcium site venipuncture causing swelling initially soft progressed hard left hand eventually diagnosed case iatrogenic calcinosis cutis due intravenous calcium treatmentconclusionthere multiple differential diagnoses calcinosis cutis resembles many conditions careful historytaking physical examination investigations radiological investigations will aid reaching accurate diagnosis thus early treatment intervention frequently checking intravenous line diluting intravenous calcium may help reduce occurrence iatrogenic calcinosis cutis,0.0
reality multiple sclerosis assessment middleincome countries authors#39 reply ,0.0
tfe3associated perivascular epithelioid cell tumor complete response mtor inhibitor therapy report first case literature review background perivascular epitheloid cell tumor pecomas characterized expression muscles often smooth muscle actin 80 cases melanocytic markers mainly hmb45 melan tfe 3associated pecomas new variant poorly defined due limited reports literature tumors lack response targeted mtor inhibitor therapy due lack mutation tsc gene hereby reporting case tfe3 associated pelvic pecoma showing excellent response everolimuscase presentationa 45yearold female presented complaint abdominal mass bleeding per vaginum 4 months history total abdominal hysterectomy 3 years back view abnormal uterine bleeding exploratory laprotomy 7 months back remove pelvic mass imaging suggested illdefined heterogenous mass 93 x 92 x 16 cm involving uterus cervix upper 1 3 vagina multiple omental peritoneal deposits also seen making probable diagnosis carcinoma endometrium usg guided biopsy showed cores fibrous tissue presence cells sheets granular eosinophillic cytoplasm ihc showed positivity tfe3 h caldesmon gata3 melan hmb45 ki 67 index 35 basis diagnosis pecoma made started everolimus repeat imaging 3 months therapy showed complete responseconclusionwe reporting first case malignant pelvic tfe 3 pecoma showing response mtor therapy identification tfe 3 pecoma important showed different biologic behavior conventional pecoma,0.0
p70s6 kinase regulates oligodendrocyte differentiation active remyelinating lesions brain commun 2022 feb 12 4 1 fcac025 doi 101093 braincomms fcac025 ecollection 2022abstractthe p70 ribosomal s6 kinases p70 ribosomal s6 kinase 1 p70 ribosomal s6 kinase 2 downstream targets mechanistic target rapamycin signalling pathway p70 ribosomal s6 kinase 1 specifically demonstrated functions regulating cell size drosophila insulinsensitive cell populations mammals prior studies demonstrated mechanistic target rapamycin pathway promotes oligodendrocyte differentiation developmental myelination however immediate downstream targets mechanistic target rapamycin regulate processes elucidated tested hypothesis p70 ribosomal s6 kinase 1 regulates oligodendrocyte differentiation developmental myelination remyelination processes cns demonstrate p70 ribosomal s6 kinase activity peaks oligodendrocyte lineage cells time transition myelinating oligodendrocytes developmental myelination mouse spinal cord show p70 ribosomal s6 kinase activity differentiating oligodendrocytes acute demyelinating lesions induced lysophosphatidylcholine injection experimental autoimmune encephalomyelitis mice demyelinated lesions expression p70 ribosomal s6 kinase target phosphorylated s6 ribosomal protein transient highest maturing oligodendrocytes interestingly also identified p70 ribosomal s6 kinase activity oligodendrocyte lineage cells active multiple sclerosis lesions consistent predicted function promoting oligodendrocyte differentiation demonstrate specifically inhibiting p70 ribosomal s6 kinase 1 cultured oligodendrocyte precursor cells significantly impairs cell lineage progression expression myelin basic protein finally used zebrafish show vivo inhibiting p70 ribosomal s6 kinase 1 function oligodendroglial cells reduces differentiation number myelin internodes produced data reveal essential function p70 ribosomal s6 kinase 1 promoting oligodendrocyte differentiation development remyelination across multiple speciespmid35224490 pmcpmc8864467 doi101093 braincomms fcac025,1.0
smartphone application exploratory endpoint phase 3 parkinson#39 s disease clinical trial pilot study digit biomark 2022 jan 10 6 1 18 doi 101159 000521232 ecollection 2022abstractbackground smartphones can generate objective measures parkinsons disease pd supplement traditional inperson rating scales however smartphone use clinical trials limitedobjective study aimed determine feasibility introducing smartphone research application pd clinical trial evaluate resulting measuresmethods smartphone application introduced partway phase 3 randomized clinical trial inosine application included finger tapping gait cognition tests participants asked complete assessment battery home clinic alongside movement disorder societyunified parkinsons disease rating scale mdsupdrs results 236 eligible participants parent study 88 37 consented participate 59 27 randomized inosine 32 placebo completed baseline smartphone assessment 59 participants collectively completed 1 292 batteries assessments proportion participants completed least one smartphone assessment 61 3 54 6 35 12 months finger tapping speed correlated weakly part iii motor portion r 016 left hand r 004 right hand total r 014 mdsupdrs gait speed correlated better measures r 025 part iii motor r 034 total 6 months finger tapping speed gait speed memory scores differ randomized active drug placeboconclusions introducing smartphone application midway phase 3 clinical trial challenging measures bradykinesia gait speed correlated modestly traditional outcomes consistent studys overall findings found benefit active drugpmid35224425 pmcpmc8832247 doi101159 000521232,0.0
msdriven metabolic alterations recapitulated ipscderived astrocytes ann neurol 2022 feb 28 doi 101002 ana26336 online ahead printabstractobjective astrocytes play significant role pathology multiple sclerosis ms nevertheless ethical reasons studies cells performed using experimental autoimmune encephalomyelitis model significant differences human mouse cells aimed better characterize astrocytes patients ms pwms focusing mainly mitochondrial function cell metabolismmethods obtained characterized induced pluripotent stem cell ipsc derived astrocytes three pwms three unaffected controls performed electron microscopy flow cytometry cytokine glutamate measurements gene expression situ respiration metabolomics validated findings using singlenuclei rna sequencing datasetresults detected several differences ms astrocytes including enrichment genes associated neurodegeneration ii increased mitochondrial fission iii increased production superoxide msrelated proinflammatory chemokines iv impaired uptake enhanced release glutamate v increased electron transport capacity proton leak line increased oxidative stress vi distinct metabolic profile deficiency amino acid catabolism increased sphingolipid metabolism already linked msinterpretation describe metabolic profile ipscderived astrocytes pwms validate model powerful tool study disease mechanisms perform noninvasive drug targeting assays vitro findings recapitulate several disease features described patients provide new mechanistic insights metabolic rewiring astrocytes ms targeted future therapeutic studies article protected copyright rights reservedpmid35226368 doi101002 ana26336,0.0
case report rapid desensitization ocrelizumab multiple sclerosis effective safe front immunol 2022 feb 9 13840238 doi 103389 fimmu2022840238 ecollection 2022abstractmonoclonal antibodies become mainstay treatment many inflammatory diseases malignancies multiple sclerosis chronic inflammatory demyelinating neurodegenerative disease central nervous system common cause disability young adults ocrelizumab recombinant humanized monoclonal antibody targets cd20positive b cells approved treatment multiple sclerosis although considered safe 30 patients treated ocrelizumab developed infusionrelated reactions mostly regarded mild severe can lead definite suspension drug present case report ocrelizumab desensitization female patient presented immediate hypersensitivity reaction urticaria angioedema first ocrelizumab infusion although mechanisms involved response elucidated procedure occurred uneventfully permitted firstline multiple sclerosis treatment maintenances desensitization considered safe therapeutic option patients immediate hypersensitivity reactions ocrelizumabpmid35222433 pmcpmc8865367 doi103389 fimmu2022840238,1.0
human herpesvirus 6a risk factor multiple sclerosis front immunol 2022 feb 10 13840753 doi 103389 fimmu2022840753 ecollection 2022abstractthe role human herpesvirus hhv 6a hhv6b multiple sclerosis ms pathogenesis controversial possibly damage virus infection may occur onset clinical symptoms difficult detect active infection separate serological responses hhv6a 6b recent studies report ms patients serological response hhv6a increased whereas decreased hhv6b effect seems even pronounced ms patients prior diagnosis supports previous studies postulating predomination hhv6a ms disease suggests infection important early stages disease furthermore hhv6a infection interacts factors suspected modulating ms susceptibility progression infection epsteinbarr virus ebv cytomegalovirus cmv tobacco smoking hla alleles uv irradiation vitamin d levels multifactorial nature ms pathophysiological role hhv6a inflammation autoimmunity discussedpmid35222435 pmcpmc8866567 doi103389 fimmu2022840753,0.0
incidence pediatric multiple sclerosis iran within 20002019 iran j child neurol 2022 winter 16 1 3138 doi 1022037 ijcnv16i135572 epub 2022 jan 1abstractobjectives due lack data pediatric multiple sclerosis ms epidemiology iran study aimed determine incidence rate pediatric ms iranmaterials methods data patients ms registered ministry health medical education iran 20 years collected study born 1982 diagnosed disease treated since 2000 included study therefor collected variables patients age time diagnosis gender year diagnosis urban rural residency province residence additionally agespecific incidence rates per 100 000 population calculatedresults study performed 4544 cases pediatric ms within 20002019 997 patients 219 male mean age patients ms time diagnosis 14346 years 4414 children 971 lived urban areas incidence rate pediatric ms iran 20 years increased 026 per 100 000 population 2000 153 2019conclusion incidence pediatric ms iran high development diagnostic practices past decade iran contributed detection high incidencepmid35222655 pmcpmc8753005 doi1022037 ijcnv16i135572,0.0
methylprednisoloneinduced symptomatic sinus bradycardia multiple sclerosis patient case report cureus 2022 jan 20 14 1 e21443 doi 107759 cureus21443 ecollection 2022 janabstractintermittent highdose methylprednisolone therapy widely used various autoimmune conditions treatment common side effects well known monitored carefully therapy although cardiovascular adverse events uncommon increasingly reported literature case 30yearold female developed symptomatic sinus bradycardia receiving three grams intravenous methylprednisolone pulse therapy multiple sclerosis flareups pulse rate reached 40bpm together lightheadedness chest tightness electrocardiogram confirmed sinus bradycardia initially managed splitting methylprednisolone dose half however 12 hours later heart rate decreased 35bpm symptoms worsened subsequently medicine omitted patient shifted intensive care unit close observation monitoring treated conservatively close observation resulted gradual normalization heart rate diagnosis methylprednisolone pulseinduced bradycardia made excluding common etiologies sinus bradycardia case report aims careful cardiovascular monitoring patients receiving high doses methylprednisolone due dosedependent cardiovascular riskspmid35223228 pmcpmc8857754 doi107759 cureus21443,0.0
successful desensitization alemtuzumab flow cytometric analysis peripheral blood cells j investig allergol clin immunol 2022 feb 170 doi 1018176 jiaci0795 online ahead printno abstractpmid35225791 doi1018176 jiaci0795,0.0
neuroimaging features associated factors multiple sclerosis patients perspective private care center addis ababa ethiopia ethiop j health sci 2021 sep 31 5 10431052 doi 104314 ejhsv31i517abstractbackground brain spine magnetic resonance image mri invaluable importance diagnosing multiple sclerosis ms low prevalence countries ethiopia objective study characterize neuroimaging features associated factors multiple sclerosis patients addis ababa ethiopiamethod crosssectional observational study conducted 30 multiple sclerosis patients yehuleshet specialty clinic addis ababa ethiopia descriptive analytical statistics used analyze dataresults enrolled 30 patients confirmed multiple sclerosis clinically isolate syndrome mean age 347 years 1sd89 female accounted 867 mean duration illness 34 years 1sd31 range 1 11 years relapsing remitting variant commonest sub type 667 alcohol use head injury commonest identified risk factors reported patients classical radiological features ms white matter lesions involving juxtacortical ufiber corpus callosum cc dawsons finger projections pattern observed 467 233 70 40 respectively cervical thoracic cords affected 40 67 respectively global cortical cc atrophy observed 167 67 respectively advanced age associated lesions corpus callosum adjusted duration illness history head injury aor 113 95 ci 101128 p004 conclusion typical neuroimaging features ms prevalent among ethiopian ms patients age independent predictor lesions involving corpus callosum global cortical atrophy common among ethiopian ms patientspmid35221622 pmcpmc8843137 doi104314 ejhsv31i517,0.0
experiences patients multiple sclerosis selfcompassion qualitative content analysis biomedicine taipei 2021 dec 1 11 4 3542 doi 1037796 221180391211 ecollection 2021abstractbackground selfcompassion enhances selfcare behavior patients multiple sclerosis concept defined previous studies however order effectively enhance patients perceptions experiences selfcompassion first understood therefore study aims explore meaning selfcompassion experienced patients multiple sclerosismethods directed qualitative study conducted 2019 iran twentythree patients multiple sclerosis selected purposefully interviewed individually qualitative content analysis used data analysis according hsieh shannons methodresults seventysix primary codes detected well following eleven categories selfkindness selfjudgment common humanity isolation mindfulness overidentification seeking support concealment spiritual resilience marital life concern turning example others categories express characteristics meaning selfcompassion patients multiple sclerosis six 11 characteristics accordance theory neffs theory five related patients cultural social arena study environmentconclusion results present study showed new dimensions selfcompassion found exploring multiple sclerosis patients experiences added suggested dimensions others study promising nurses paramedics will help better identify take better care patients result will also help design valid tool measure issue patientspmid35223417 pmcpmc8823481 doi1037796 221180391211,0.0
macromolecular proton fraction myelin biomarker principles validation applications front neurosci 2022 feb 9 16819912 doi 103389 fnins2022819912 ecollection 2022abstractmacromolecular proton fraction mpf quantitative mri parameter describing magnetization transfer mt effect defined relative amount protons bound biological macromolecules restricted molecular motion participate magnetic crossrelaxation water protons mpf attracted significant interest past decade biomarker myelin purpose mini review provide brief comprehensive summary mpf mapping methods histological validation studies mpf applications neuroscience technically mpf maps can obtained using variety quantitative mt methods enable clinically reasonable scan time resolution recent studies demonstrated feasibility mpf mapping using standard clinical mri pulse sequences thus substantially enhancing method availability number studies animal models demonstrated strong correlations mpf histological markers myelin minor influence potential confounders histological studies validated capability mpf monitor demyelination remyelination clinical applications mpf mainly focused multiple sclerosis method provided new insights white gray matter pathology besides several studies used mpf investigate myelin role neurological psychiatric conditions another promising area mpf applications brain development studies mpf demonstrated capabilities quantitatively characterize earliest stage myelination prenatal brain maturation protracted myelin development adolescence summary mpf mapping provides technically mature comprehensively validated myelin imaging technology various preclinical clinical neuroscience applicationspmid35221905 pmcpmc8863973 doi103389 fnins2022819912,1.0
cohesinmediated chromatin interactions autoimmunity front immunol 2022 feb 10 13840002 doi 103389 fimmu2022840002 ecollection 2022abstractproper physiological functioning cell type requires ordered chromatin organization context cohesin complex performs important functions preventing premature separation sister chromatids dna replication partnership ccctcbinding factor ensures insulator activity organize enhancers promoters within regulatory chromatin homozygous mutations dysfunction individual cohesin proteins embryonically lethal humans mice limits vivo research work embryonic stem cells progenitors conditional alleles cohesin complex proteins generated investigate functional roles greater detail later developmental stages thus genome regulation enabled action cohesin proteins potentially crucial lineage cell development including immune homeostasis review provide current knowledge role cohesin complex leukocyte maturation adaptive immunity conditional knockout shrnamediated inhibition individual cohesin proteins mice demonstrated importance haematopoiesis adipogenesis inflammation notably effects occur rather changes transcriptional gene regulation expected cell cycle defects positions cohesin crossroad immune pathways including nfkb il6 ifn signaling cohesin proteins emerged vital regulators early developmental stages thymocytes b cells antigen challenge human genomewide association studies remarkably concordant findings present associations cohesin rheumatoid arthritis multiple sclerosis hlab27 related chronic inflammatory conditions furthermore bioinformatic prediction based proteinprotein interactions reveal tight connection cohesin complex immune relevant processes supporting notion cohesin will unearth new clues regulation autoimmunitypmid35222432 pmcpmc8866859 doi103389 fimmu2022840002,0.0
double versus triple arthrodesis fusion rates systematic review j foot ankle surg 2022 jan 19s10672516 22 000126 doi 101053 jjfas202201012 online ahead printabstracthindfoot arthrodesis often required endstaged deformities posterior tibial tendon dysfunction osteoarthritis rheumatoid arthritis although need hindfoot arthrodesis generally accepted severe deformities debate whether double triple arthrodesis performed aim systematic review review fusion rates mean time fusion double triple arthrodesis total 184 articles identified using keyword search database articles published 2005 2017 review 3 physicians total 13 articles met eligibility criteria reason double triple arthrodesis within studies posterior tibial tendon dysfunction tarsal coalition degenerative joint disease osteoarthritis rheumatoid arthritis charcot marie tooth multiple sclerosis polio neuromuscular disorder cerebral palsy acrodystrophic neuropathy clubfoot posttraumatic seronegative arthropathy spondyloarthritis within 13 studies total 343 695 subjects extremities operated overall fusion rate double arthrodesis 9175 289 315 compared 9286 26 28 triple arthrodesis fusion rate p value 8370 mean time fusion double arthrodesis 1796 796 weeks compared 1670 818 weeks triple arthrodesis p value 8133 risks associated triple arthrodesis including increased surgical times lateral wound complications residual deformity surgical costs periarticular arthritis given benefits double arthrodesis triple arthrodesis nearly equivalent fusion rates time fusion double arthrodesis effective alternative triple arthrodesis authors systematic review recommend double arthrodesis hindfoot fusion procedure choicepmid35221217 doi101053 jjfas202201012,0.0
dissection immunohistochemistry drosophila adult leg detect changes neuromuscular junction identified motor neuron j vis exp 2022 feb 12 180 doi 103791 62844abstractdrosophila melanogaster represents genetically tractable model study neuronal structure function subsequent changes disease states well characterized larval neuromuscular junction often used studies however rapid larval development followed muscle histolysis nervous system remodeling metamorphosis makes model problematic study slow agedependent degenerative changes like occurring amyotrophic lateral sclerosis alternatively adult flies live 90 days adult leg can used study motor neuron changes course adult lifespan using vivo fluorescent imaging cuticle describe leg dissection technique coupled immunocytochemistry allows study molecular changes neuromuscular junction identified adult leg motor neurons techniques can coupled myriad antibodies labeling pre postsynaptic structures together procedures allow complete characterization slow agedependent changes adult flies can applied across multiple motor neuron disease modelspmid35225252 doi103791 62844,0.0
qingda granule attenuates angiotensin iiinduced renal apoptosis activation p53 pathway front pharmacol 2022 feb 10 12770863 doi 103389 fphar2021770863 ecollection 2021abstractbackground qingda granules qdg exhibit antihypertension multipletargetorgan protection however therapeutic potential qdg hypertensive renal injury remains unknown therefore main objective current study explore effects underlying mechanisms qdg treatment renal injury angiotensin ang iiinfused mice methods results mice infused ang ii 500 ng kg min saline 4 weeks subcutaneously implanted osmotic pumps infusion mice ang ii + qdg group intragastrically administrated qdg daily 1145 g kg day whereas control group ang ii group intragastrically administrated amount doubledistilled water blood pressure mice monitored using coda noninvasive blood pressure system revealed qdg treatment significantly attenuated elevated blood pressure moreover hematoxylineosin staining indicated qdg treatment ameliorated ang iiinduced renal morphological changes including glomerular sclerosis atrophy epithelial cell atrophy tubular dilatation rnasequencing rnaseq identified 662 differentially expressed transcripts dets renal tissues ang iiinfused mice reversed qdg treatment kyoto encyclopedia genes genomes kegg analysis based dets comparisons ang ii vs control ang ii + qdg vs ang ii identified multiple enriched pathways including apoptosis p53 pathways consistently terminal deoxynucleotidyl transferase tdt dutp nickend labeling tunel staining annexin v staining revealed qdg treatment significantly attenuated ang iiinduced cell apoptosis renal tissues cultured renal tubular epithelial cell lines nrk52e furthermore western blot analysis indicated ang ii infusion significantly upregulated protein expression p53 bcl2associated x bax clecaspase9 clecaspase3 downregulating protein expression bcl2 renal tissues attenuated qdg treatment conclusion collectively qdg treatment significantly attenuated hypertensive renal injury partially attenuating renal apoptosis suppressing p53 pathways might underlying mechanismspmid35222007 pmcpmc8867011 doi103389 fphar2021770863,0.0
recent considerations gaming console based training multiple sclerosis rehabilitation med sci basel 2022 feb 11 10 1 13 doi 103390 medsci10010013abstractmultiple sclerosis ms wellknown chronic demyelinating disease central nervous system cns one common causes disability young adults context one major challenges patients rehabilitation maintain gained motor abilities terms functional independence partially obtained applying new emerging cuttingedge virtual augmented reality serious game technologies playful noninvasive treatment demonstrated quite efficient effective enhancing clinical status patients re integration society recently cloud computing internet things iot emerged technologies can potentially revolutionize patients care achieve goal system one hand gathers patients clinical parameters network medical iot devices equipped sensors hand sends collected data hospital cloud processing analytics required paper assess effectiveness nintendo wii fit plus balance board wfbb used iot medical device adopted rehabilitation training program aimed improving physical abilities ms patients pwms particular main scientific contribution paper twofold present preliminary new pilot study investigating whether exercises based nintendo wii fit balance board included rehabilitation training program improve physical abilities quality life qol patients compared conventional fourweek rehabilitation training program ii discuss rehabilitation training program adopted perspective near future networks medical iotbased rehabilitation devices interconnected hospital cloud system big data processing improve patients therapies support scientific research motor rehabilitation results demonstrate advantages approach health technological points viewpmid35225946 doi103390 medsci10010013,1.0
case neuromyelitis optica puerto rican woman increased time lag diagnosis high response eculizumab therapy case rep neurol med 2022 feb 18 20224311382 doi 101155 2022 4311382 ecollection 2022abstracta link intractable hiccups initial symptom possible neuromyelitis optica spectrum disorder nmosd diagnosis confusing vital may made health care providers hcps aware 2015 nmosd criteria early diagnosis adequate treatment essential prevent disease progression report case 46yearold puerto rican female presented intractable hiccups 31 2004 almost 15 years passed since initial symptom two severe relapses received formal nmosd diagnosis march 2019 treatment started rituximab 1000 mg iv april 2019 however lack response treatment led switch eculizumab therapy august 2019 patient cervical brain magnetic resonance imaging mri conducted june 2020 depicted remarkable decrease swelling hyperintensity within cervical spinal cord enhancing lesions compared first mri february 2019 addition patient suffered new relapses improvement regarding disability reduction cervical spinal cord lesion size nonetheless substantial decrease occur nmosd patients awareness disease needed especially puerto rico case illustrates efficacy eculizumab therapy importance differentiating clinical histopathological neuroimaging characteristics separate demyelinating autoimmune inflammatory disorders nmosd multiple sclerosis ms pmid35223117 pmcpmc8881169 doi101155 2022 4311382,1.0
interventions instrumental activities daily living among adults multiple sclerosis systematic review j occup ther 2022 mar 1 76 2 7602205130 doi 105014 ajot2022049092abstractimportance occupational therapy practitioners need updated information interventions may improve maintain functional changes instrumental activity daily living iadl engagement caused multiple sclerosis ms objective conduct narrative synthesis updated evidence interventions within scope occupational therapy improve maintain performance participation iadls among adults msdata sources cinahl medline pubmed cochrane otseeker psycinfo study selection data collection systematic review followed cochrane collaboration methodology reported according preferred reporting items systematic reviews metaanalyses prisma guidelines conducting systematic review inclusion criteria level 1 2 evidence published english published january 2011 december 2018 intervention within occupational therapy scope practice least one iadl outcome measurefindings nineteen randomized controlled trials including pilot feasibility trials 1 preinterventionpostintervention study met inclusion criteria results review show strong strength evidence coaching interventions addressing physical activity pa routines moderate support addressing medication routines moderate strength evidence found mixed results interventions involving coaching plus prescribed pa improving pa participationconclusions relevance systematic review supports occupational therapy practitioners addressing pa medication health management maintenance iadls use coaching interventions treating people ms iadls addressed articles review require evidence make clinical recommendations article adds occupational therapy practitioners skills promoting habits routines paired utilization evidencesupported coaching interventions can support independence health management reduce negative impact ms daily activity participationpmid35226064 doi105014 ajot2022049092,0.0
relationship optical coherence tomography angiography visual evoked potential patients multiple sclerosis indian j ophthalmol 2022 mar 70 3 873878 doi 104103 ijoijo_431_21abstractpurpose study aimed identify easytoapply biomarker correlating visual evoked potential vep optical coherence tomography angiography octa results multiple sclerosis ms methods study planned prospectively patients ms divided two groups vep prolonged group 1 vep normal group 2 agematched gendermatched healthy individuals group 3 included control group vascular density vd optic nerve head onh radial peripapillary capillaries rpcs measured recorded octa optic nerve damage patients measured recorded vep deviceresults thirtytwo eyes included group 1 50 eyes included group 2 51 healthy eyes included group 3 terms visual acuity group 1 significantly lower groups p 0001 regardless prolongation p100 latency patients ms whole image inside disc onh vd sectors rpc vd found significantly lower control group p 005 retinal nerve fiber layer thickness found significantly lower group 1 group 2 group 3 p 005 significant correlation low onh vd rpc vd prolonged vep p100 p 005 conclusion vep measurements can correlated octa measurements patients ms can used biomarker determine degree optic nerve damagepmid35225535 doi104103 ijoijo_431_21,0.0
association dairy intake migraine odds among pediatrics adolescents casecontrol study iran j child neurol 2022 winter 16 1 105122 doi 1022037 ijcnv15i43062 epub 2022 jan 1abstractobjective migraine recognized disease unknown etiology various pathophysiologic pathways fully understood due relation dairy intake various chronic conditions children also paucity data probable role dairy intake pediatrics odds migraine study designedmaterials methods present study populationbased casecontrol design accomplished tertiary headache clinic290 child aged from7 14 years old included study definite diagnosis migraine performed neurologist concerning 2018 international classification headache disorder 3 ichd3 criteria also demographic anthropometric characteristics obtained addition usual dietary intake participants evaluated using validated semiquantitative food frequency questionnaire ffq results children case group significantly higher age bmi means pvalue0000 second regression model odds migraine 48 052 95ci027100 diminished second tertile 53 or047 95ci024092 third tertile lowfat dairy intake ptrend003 fully adjusted model achieved migraine ors followings048 95 ci024095 second tertile 046 95 ci021096 third tertile ptrend004 respectively children highfat dairy intake also consumed higher amounts energy pastries simple sugar unhealthy snacks hydrogenated oil p005 conclusion study results proposed greater amount lowfat dairy intake may attenuate odds migraine attacks pediatrics adolescents might risk headache can attributed micronutrient also bioactive content dietary componentspmid35222662 pmcpmc8753001 doi1022037 ijcnv15i43062,0.0
extended interval dosing natalizumab impact neuropsychological deficits relapsingremitting multiple sclerosis mult scler j exp transl clin 2022 feb 23 8 1 20552173211070752 doi 101177 20552173211070752 ecollection 2022 janmarabstractbackground cognitive impairment neuropsychiatric symptoms frequently reported relapsingremitting multiple sclerosis rrms natalizumab ntz usually administered 4weekly standard interval dosing sid schedule however extended interval dosing eid 68 weekly intervals proven noninferior regarding relapse risk lower risk progressive multifocal leukoencephalopathy pml impact eid ntz neuropsychological deficits rrms studied objective determine eid ntz demonstrates improvement neuropsychological parameters rrms patients method performed retrospective observational analysis 34 rrms patients treated august 20152017 patients underwent baseline neuropsychological testing commencing eid ntz second evaluation performed average 28 months commencing treatment results z scores initial assessment showed baseline cognitive impairment multiple domains 14 20 zscores showed improvement postntz 5 14 reached statistical significance namely trails visual attention processing speed lineorientation visualspatial picturenaming word finding digitalspan attention executive function memory storyrecall memory hospital anxiety depression scale hads data remained unchanged correlation matrix showed association hads scores time assessments changes z scores conclusion data suggests efficacy eid ntz improving cognitive impairment rrms prospective observational study warrantedpmid35223079 pmcpmc8874183 doi101177 20552173211070752,0.0
acute cerebellitis requiring posterior fossa decompression covid19 vaccination ocrelizumabtreated patient multiple sclerosis neurol sci 2022 feb 28 doi 101007 s10072022059664 online ahead printno abstractpmid35226212 doi101007 s10072022059664,0.0
fractal analysis quantification medical imaging associated multiple sclerosis pathology front biosci landmark ed 2022 feb 14 27 2 66 doi 1031083 jfbl2702066abstractbackgrounds multiple sclerosis ms inveterate phlogistic situation characterized focal vaguely diffusive demyelination neurodegeneration sphere central nervous system cns brains chronic inflammatory reaction includes astrocyte stimulation microglial motivation well macrophages marginal conscription lasting serious soreness brain connected neurodegeneration period disability advancemethods present study considering two main purposes follows primarily apply fractal analysis idea documenting fractals dominance stages nervous system hierarchy giving faith precept funciar relevancy secondly take account problems unresolved thorough connections selforganized criticality concept selfsimilarity notion precisely reality will obtain information fractal size lacunarity magnetic resonance imaging mri areas interest brain rich microglial cells fringes peripheral macrophages cellsresults approach will play decisive role action detecting neural disabilities particular multiple sclerosis cortical onset final goal investigation diagnosis based interpretation histological sample pictures images obtained nuclear magnetic resonance using fractal analysis calculated image separately fractal dimension lacunarity objective quantitative measure demyelinating actionconclusions three histopathological samples glial cells visible erosions fractal dimension value 189 lacunarity value 0050 0079 gray level stages studied mri pictures fractal dimension value 17 lacunarity values 00286 00393pmid35227009 doi1031083 jfbl2702066,1.0
guide diagnosis rare undiagnosed disease beyond exome abstractrare diseases affect 30 million people usa 300400 million worldwide often causing chronic illness disability premature death traditional diagnostic techniques rely heavily heuristic approaches coupling clinical experience prior rare disease presentations medical literature large number rare disease patients remain undiagnosed years many even die without accurate diagnosis recent years gene panels microarrays exome sequencing helped identify molecular cause rare undiagnosed diseases technologies allowed diagnoses sizable proportion 2535 undiagnosed patients often actionable findings however large proportion patients remain undiagnosed review focus technologies can adopted exome sequencing unrevealing discuss benefits sequencing whole genome additional benefit may offered longread technology pangenome reference transcriptomics metabolomics proteomics methyl profiling highlight computational methods help identify regionally distant patients similar phenotypes similar genetic mutations finally describe approaches automate accelerate genomic analysis strategies discussed intended serve guide clinicians researchers next steps encountering patients nondiagnostic exomes,0.0
intraarterial application nimodipine reversible cerebral vasoconstriction syndrome neuroradiological method help differentiate primary central nervous system vasculitis background reversible cerebral vasoconstriction syndrome rcvs characterized prolonged selflimiting segmental cerebral vasoconstriction neurological outcomes vary can severe clinical hallmark rcvs thunderclap headache might come along neurological symptoms distinguishing rcvs entities primary angiitis central nervous system pacns utmost importance appropriate therapy angiographic response intraarterial nimodipine application suggested additional diagnostic criterion rcvs confirmatory studies limited aimed evaluate angiographic nimodipine testmethodswe reviewed retrospectively clinical imaging data 13 rcvs patients admitted single german neurological department january 2013 december 2020resultsout 13 patients diagnosed rcvs 4 patients underwent angiographic nimodipine test 4 patients cerebral vasoconstriction completely resolved nimodipine application among four patients positive test one individual response detected delay 60 min patients found complete resolution cerebral vasoconstriction within 12 weeksconclusionour findings support usefulness application nimodipine diagnosing rcvs prolonged angiographic observation vascular response nimodipine injection important,0.0
neurovascular unit leukodystrophies towards solving puzzle abstractthe neurovascular unit nvu highly organized multicellular system localized brain formed neuronal glial astrocytes oligodendrocytes microglia vascular endothelial cells pericytes cells bloodbrain barrier complex dynamic endothelial cell barrier brain microvasculature separates blood brain parenchyma component nvu variety neurological disorders including alzheimers disease multiple sclerosis stroke dysfunctions nvu occurs however lack knowledge regarding nvu function leukodystrophies rare monogenic disorders primarily affect white matter since leukodystrophies rare diseases human brain tissue availability scarce representative animal models significantly recapitulate disease difficult develop introduction human induced pluripotent stem cells hipsc now makes possible surpass limitations maintaining ability work biologically relevant human context safeguarding genetic background patient review aims provide insights nvu functioning leukodystrophies special focus ipscderived models can used dissect neurovascular pathophysiology diseases,0.0
als monocytederived microglialike cells reveal cytoplasmic tdp43 accumulation dna damage cellspecific impairment phagocytosis associated disease progression background amyotrophic lateral sclerosis als multifactorial neurodegenerative disease characterised loss upper lower motor neurons increasing evidence indicates neuroinflammation mediated microglia contributes als pathogenesis microglial activation evident postmortem brain tissues neuroimaging data patients als however role microglia pathogenesis progression amyotrophic lateral sclerosis remains unclear partly due lack model system able faithfully recapitulate clinical pathology als address shortcoming describe approach generates monocytederived microglialike cells capable expressing molecular markers functional characteristics similar vivo human brain microgliamethodsin study established monocytederived microglialike cells 30 sporadic patients als including 15 patients slow disease progression 6 intermediate progression 9 rapid progression together 20 nonaffected healthy controlsresultswe demonstrate patient monocytederived microglialike cells recapitulate canonical pathological features als including nonphosphorylated phosphorylatedtdp43positive inclusions moreover als microglialike cells showed significantly impaired phagocytosis altered cytokine profiles abnormal morphologies consistent neuroinflammatory phenotype interestingly als microglialike cells showed abnormal phagocytosis consistent progression disease indepth analysis als microglialike cells rapid disease progression cohort revealed significantly altered cellspecific variation phagocytic function addition dna damage nodleucine rich repeat pyrin containing protein 3 nlrp3 inflammasome activity also elevated als patient monocytederived microglialike cells indicating potential new pathway involved driving disease progressionconclusionstaken together work demonstrates monocytederived microglialike cell model recapitulates diseasespecific hallmarks characteristics substantiate patient heterogeneity associated disease subgroups thus monocytederived microglialike cells highly applicable monitor disease progression can applied functional readout clinical trials antineuroinflammatory agents providing basis personalised treatment patients als,0.0
genome variation tick infestation cryptic divergence tunisian indigenous sheep background ticks obligate haematophagous ectoparasites considered second mosquitos vectors reservoirs multiple pathogens global concern individual variation tick infestation reported indigenous sheep genetic control remains unknownresultshere report 397 genomewide signatures selection overlapping 991 genes analysis using roh lrgwas xpehh fst 600 k snp genotype data 165 tunisian sheep showing high low levels tick infestations piroplasm infections consider 45 signatures detected consensus results least two methods highconfidence selection regions spanned 104 genes included immune system function genes solute carriers chemokine receptor one region spanned stx5 associated tick resistance cattle implicating prime candidate sheep also observed rab6b tf high confidence candidate region associated growth traits suggesting natural selection enhancing growth developmental stability tick challenge analysis also revealed finescale genome structure indicative cryptic divergence tunisian sheepconclusionsour findings provide genomic reference can enhance understanding genetic architecture tick resistance cryptic divergence indigenous african sheep,0.0
senescent skeletal cells crosstalk synovial cells plays key role pathogenesis osteoarthritis abstractosteoarthritis oa recognized agerelated degenerative disease commonly seen elderly affects whole organ including cartilage subchondral bone synovium muscles increasing number studies suggested accumulation senescent cells triggering various stresses local joint contributes pathogenesis agerelated diseases including oa review mainly focus role senescent skeletal cells chondrocytes osteoblasts osteoclasts osteocyte muscle cells initiating development progression oa alone crosstalk macrophages synovial cells accordingly summarize current oatargeted therapies based abovementioned theory eg eliminating senescent skeletal cells inhibiting senescenceassociated secretory phenotype sasp drives senescence furthermore existing animal models study oa perspective senescence highlighted fill gap basic research clinical applications overall review systematically assess current understanding cellular senescence oa turn might shed light stratified oa treatments,0.0
control charts chronic disease surveillance testing algorithm sensitivity changes data coding background algorithms used identify disease cases administrative health data may sensitive changes data time control charts can used assess variations administrative health data impact stability estimated trends incidence prevalence administrative data algorithms compared stability incidence prevalence trends multiple juvenile diabetes algorithms using observedexpected control chartsmethodseighteen validated algorithms juvenile diabetes applied administrative health data manitoba canada 1975 2018 trends disease incidence prevalence algorithm modelled using negative binomial regression generalized estimating equations modelpredicted case counts plotted observed counts control limits set predicted case count 08standard deviation differences frequency outofcontrol observations algorithm assessed using mcnemars test holmbonferroni adjustmentresultsthe proportion outofcontrol observations incidence prevalence ranged 057 076 045 083 respectively mcnemars test revealed difference frequency outofcontrol observations across algorithms sensitivity analysis relaxed control limits 2standard deviation detected fewer outofcontrol years incidence 019 033 prevalence 007 052 differences stability across algorithms prevalenceconclusionsour study using control charts compare stability trends incidence prevalence juvenile diabetes algorithms found differences disease incidence differences observed select algorithms disease prevalence using wider control limits,0.0
ccr1 antagonist ameliorates experimental autoimmune encephalomyelitis inhibition th9#x2f th22related markers brain periphery mol immunol 2022 feb 24 144127137 doi 101016 jmolimm202202017 online ahead printabstractmultiple sclerosis ms immunemediated disease central nervous system disease manifestation associated proliferation activation lymphocytes astrocytes leading demyelination neuronal damage current therapies completely effective target underlying pathophysiology ms t helper 9 th9 th22dominant cells proven play pathogenic role experimental autoimmune encephalomyelitis eae animal model ms goal present study investigate therapeutic efficacy j113863 novel ccr1 chemokine receptor plp139151induced eae sjl j mice following induction eae mice treated j113863 10 mg kg saline intraperitoneally daily day 14 day 25 clinical score evaluated investigated effect j113863 il9 irf4 il22 ifn stat3 ahr il17a cd3+ cd4+ ccr6+ ccr8+ spleen cells using flow cytometry also analyzed effect j113863 il9 irf4 il22 ifn stat3 ahr il17a mrna expression levels results revealed j113863 treatment notably attenuated severity clinical scores eae mice j113863 treatment decreased percentage expression cd4+il9+ ccr8+il9+ cd4+irf4+ cd3+il22+ ccr6+il22+ cd3+ifn+ ccr6+ifn+ cd3+stat3+ ccr6+stat3+ cd4+il17a+ ccr6+il17a+ increased percentage cd3+ahr+ ccr6+ahr+ cells spleen results confirmed j113863 suppressed th9 th22 cells reduce demyelination eae mice suggesting potential role novel drug candidate ms treatmentpmid35219910 doi101016 jmolimm202202017,1.0
evaluation unsupervised 30second chair stand test performance assessed wearable sensors predict fall status multiple sclerosis gait posture 2022 feb 23 941925 doi 101016 jgaitpost202202016 online ahead printabstractbackground one two people multiple sclerosis pwms will fall threemonth period predicting patients will fall remains challenge clinicians standardized functional assessments provide insight balance deficits fall risk use limited supervised visitsresearch question study aim characterize unsupervised 30second chair stand test 30cst performance using accelerometerderived metrics assess ability classify fall status pwms compared supervised 30cstmethods thirtyseven pwms 21 fallers performed instrumented supervised unsupervised 30csts single wearable sensor thigh unsupervised conditions participants performed bihourly 30csts rated balance confidence fatigue 48hours roc analysis used classify fall status 30cst performanceresults nonfallers p 002 fallers p 023 differed average unsupervised 30cst performance repetitions compared supervised performance unsupervised maximum number 30cst repetitions performed optimized roc classification auc 079 accuracy 784 specificity 900 fall status optimal cutoff 17 repetitionssignificance brief durations instrumented unsupervised monitoring adjunct routine clinical assessments improve ability predicting fall risk fluctuations functional mobility pwmspmid35220031 doi101016 jgaitpost202202016,0.0
rare tremors tremors occurring neurological disorders j neurol sci 2022 feb 19 435120200 doi 101016 jjns2022120200 online ahead printabstractalthough tremor deemed commonest movement disorder adults differential diagnosis usually boils whether patient essential tremor parkinsons disease likely led overdiagnosis conditions yet many important rare syndromes considered differential diagnosis patients tremor aim review focus rare forms tremor also view new tremor classification well tremor occurring neurological disorders aid recognition conditions reviewed treatable therefore missed review includes orthostatic tremor focal taskspecific tremors holmes tremor palatal oculopalatal tremor cortical tremor genetic forms tremor including fragile xassociated tremor ataxia syndrome well tremor associated neuromuscular disorders multiple sclerosis wilsons disease providing array demonstrative videos recognition disorders aid physician make correct diagnosis guide prompt interventionpmid35220114 doi101016 jjns2022120200,0.0
comparison machine learning methods using spectralis oct diagnosis disability progression prognosis multiple sclerosis ann biomed eng 2022 feb 26 doi 101007 s10439022029303 online ahead printabstractmachine learning approaches diagnosis prognosis multiple sclerosis ms analysed using retinal nerve fiber layer rnfl thickness measured optical coherence tomography oct crosssectional study 72 ms patients 30 healthy controls used diagnosis 72 ms patients involved 10year longitudinal followup study prognostic purposes structural measurements rnfl thickness performed using different spectralis oct protocols fast macular thickness protocol measure macular rnfl fast rnfl thickness protocol fast rnfln thickness protocol measure peripapillary rnfl binary classifiers multiple linear regression mlr support vector machines svm decision tree dt knearest neighbours knn nave bayes nb ensemble classifier ec long shortterm memory lstm recurrent neural network tested ms diagnosis best acquisition protocol fast macular thickness protocol using knn accuracy 958 sensitivity 944 specificity 972 precision 971 auc 0958 ms prognosis model 3year follow predict disability progression 8 years later best predictive model dt performed best fast macular thickness protocol accuracy 913 sensitivity 900 specificity 925 precision 923 auc 0913 svm fast rnfln thickness protocol accuracy 913 sensitivity 875 specificity 950 precision 946 auc 0913 work concludes measurements rnfl thickness obtained spectralis oct good ability diagnose ms predict disability progression ms patients machine learning approach help clinicians valuable informationpmid35220529 doi101007 s10439022029303,0.0
interstitial lung disease primary sjgren#39 s syndrome background interstitial lung disease ild may cause lifethreatening complications primary sjogrens syndrome pss poor prognosis terms survival quality life date studies investigated risk factors ild detected highresolution computed tomography hrct pss patients without respiratory symptomsmethodsdata 333 patients newly diagnosed pss retrospectively analysed interstitial lung disease involvement defined typical abnormalities hrct pulmonary function tests multivariate regression model used evaluate association interstitial lung disease pss characteristicsresultssixtysix patients 1982 diagnosed pssild ground glass opacities 8788 septal sub pleural lines 8182 frequent based pulmonary highresolution computed tomography patients divided nonspecific n 42 usual n 20 lymphocytic interstitial pneumonia n 3 cryptogenic organising pneumonia n 1 groups strong association erythrocyte sedimentation rate esr creactive protein crp hrctscore pulmonary function tests revealed impaired diffusion capacity carbon monoxide total lung capacity coexistence small airway lesions pssinterstitial lung disease logistic regression analysis age raynauds phenomenon lymphopenia cough dyspnoea rampant dental caries risk factors associated pssinterstitial lung diseaseconclusionsinterstitial lung disease involvement pss common clinical occurrence clinical manifestation nonspecific variable raynauds phenomenon lymphopenia may predict onset pss patients advanced age dry cough dyspnoea systematically evaluated ild involvement managed according symptoms,0.0
choroid plexus volume multiple sclerosis vs neuromyelitis optica spectrum disorder retrospective crosssectional analysis neurol neuroimmunol neuroinflamm 2022 feb 25 9 3 e1147 doi 101212 nxi0000000000001147 print 2022 mayabstractbackground objectives choroid plexus shown play crucial role cns inflammation previous studies found larger choroid plexus multiple sclerosis ms compared healthy controls however clear whether choroid plexus similarly involved ms neuromyelitis optica spectrum disorder nmosd thus aim study compare choroid plexus volume ms nmosdmethods retrospective crosssectional study patients included convenience sampling 4 international ms centers choroid plexus lateral ventricles segmented fully automatically t1weighted mri sequences using deep learning algorithm multidimensional gated recurrent units uni multivariable linear models applied investigate associations choroid plexus volume clinically meaningful disease characteristics mri parametersresults studied 180 patients ms 98 patients nmosd total 94 healthy individuals 47 patients migraine served controls choroid plexus volume larger ms median 1 690 l interquartile range iqr 648 l nmosd median 1 403 l iqr 510 l healthy individuals median 1 533 l iqr 570 l patients migraine median 1 404 l iqr 524 l p 0001 whereas difference nmosd migraine healthy controls also true adjusted age sex intracranial volume contrast nmosd choroid plexus volume ms associated number t2weighted lesions linear model adjusted age sex total intracranial volume disease duration relapses year mri disease course expanded disability status scale score diseasemodifying treatment treatment duration beta 44 95 ci 07881 p 0018 discussion study supports involvement choroid plexus ms contrast nmosd provides clues better understand respective pathogenesispmid35217580 doi101212 nxi0000000000001147,0.0
comparative effectiveness natalizumab versus anticd20 highly active relapsingremitting multiple sclerosis fingolimod withdrawal neurotherapeutics 2022 feb 25 doi 101007 s13311022012021 online ahead printabstractin france two therapeutic strategies can offered fingolimod fng withdrawal highly active relapsingremitting multiple sclerosis rrms patients natalizumab ntz anticd20 compared effectiveness two strategies switch fng within ofsep database primary endpoint time first relapse outcomes relapse rates 3month periods time worsening edss score proportion patients worsened 24month mri time treatment discontinuation incidence rates serious adverse events dynamics event rates time modeled using multidimensional penalized splines allowing possibility model effects covariates flexible way considering nonlinearity interactions total 740 patients included 337 anticd20 403 ntz difference two treatments regarding dynamic first occurrence relapse monthly probability 50 initiation 10 6 months rate edss worsening increased groups 6 months decreased difference proportion patients new t2 lesions 24 months observed 18 months followup greater risk ntz discontinuation found compared anticd20 study showed difference ntz anticd20 fng switch regarding clinical radiological activity effect treatments optimal 6 months frequent discontinuation ntz 18 months probably mainly related jc virus seroconversionspmid35217934 doi101007 s13311022012021,0.0
novel oxindole compounds inhibit aggregation amyloidogenic proteins associated neurodegenerative diseases biochim biophys acta gen subj 2022 feb 22130114 doi 101016 jbbagen2022130114 online ahead printabstractamyloidogenic proteins form aggregates cells thereby leading neurodegenerative disorders including alzheimers prions disease amyotrophic lateral sclerosis als humans degenerative myelopathy dm cognitive dysfunction dogs hence many smallmolecule compounds screened examine inhibitory effects amyloidogenic protein aggregation however effective drug suitable transition clinical use found examined several novel oxindole compounds gif compounds inhibitory effects aggregate formation canine mutant superoxide dismutase 1 csod1 e40k causative mutation resulting dm using thioflavint fluorescence gif compounds inhibited aggregation csod1 e40k among compounds gif0854r gif0890r effective inhibitory effects also observed csod1 e40ktransfected cells additionally gif0890r effectively inhibited aggregate formation human sod1 g93a causative mutation als gif0827r gif0856r also effectively inhibited aggregate formation human prion protein hprp subsequently correlation inhibitory effects csod1 hprp aggregation shown indicating gif compounds inhibited aggregate formation multiple amyloidogenic proteins conclusively novel oxindole compounds gif0827r gif0854r gif0856r gif0890r proposed useful therapeutic candidates amyloidogenic neurodegenerative disorderspmid35217127 doi101016 jbbagen2022130114,0.0
cortical subcortical changes restingstate neuronal activity connectivity early symptomatic als advanced frontotemporal dementia neuroimage clin 2022 feb 12 34102965 doi 101016 jnicl2022102965 online ahead printabstractthe objective study examine patterns restingstate brain activity functional connectivity cortical subcortical regions patients early symptomatic amyotrophic lateral sclerosis als resemble behavioural variant frontotemporal dementia bvftd crosssectional design eyesclosed restingstate magnetoencephalography meg data 34 als patients 18 bvftd patients 18 age gendermatched healthy controls hcs projected sourcespace using atlasbased beamformer group differences peak frequency bandspecific oscillatory activity functional connectivity corrected amplitude envelope correlation 78 cortical regions 12 subcortical regions determined false discovery rate used correct multiple comparisons bvftd patients compared als hcs showed lower relative beta power parietal occipital temporal nearly subcortical regions compared hcs patients als patients bvftd higher delta 054 hz gamma 3048 hz band restingstate functional connectivity high number overlapping regions frontal lobe limbic subcortical regions higher delta band connectivity widespread bvftd patients compared hcs als showed widespread higher gamma band functional connectivity compared bvftd conclusion meg early symptomatic als patients shows restingstate functional connectivity changes frontal limbic subcortical regions overlap considerably bvftd findings show potential meg detect brain changes early symptomatic phases als contribute understanding disease spectrum als bvftd two extreme endspmid35217500 doi101016 jnicl2022102965,0.0
diseasemodifying therapies t1 hypointense lesions patients multiple sclerosis systematic review metaanalysis cns neurosci ther 2022 feb 25 doi 101111 cns13815 online ahead printabstractbackground previous research shown cerebral t1 hypointense lesions positively correlated disability multiple sclerosis ms patients hence used objective marker evaluating progression disease date systematic evaluation effects diseasemodifying therapies dmts prognostic markerobjectives evaluate effects fdaapproved dmts numbers volume t1 hypointense lesions adult patients msmethods included studies mentioned desired outcomes march 2021 searched medline ovid embase central find relevant studies included studies assessed risk bias using rob2 tool extracted data analyzed using randomeffects model certainty evidence assessed using graderesults thirteen studies 7484 participants included metaanalysis revealed mean difference intervention comparator groups number lesions 13 95 ci 21 05 mean volume lesions 3631 95 ci 6116 1146 certainty evidence judged moderate heterogeneity considerablediscussion dmts reduce number volume t1 hypointense lesions although findings must interpreted cautiously due high values heterogeneitypmid35218155 doi101111 cns13815,0.0
risk disease relapse following covid19 vaccination patients aqp4iggpositive nmosd mogad mult scler relat disord 2022 feb 58103424 doi 101016 jmsard2021103424 epub 2021 nov 22abstractpostvaccination disease relapses reported patients mogad aqp4igg+nmosd retrospective multicenter italian study assessed frequency relapses sarscov2 vaccination included 56 cases mogad 30 aqp4igg+nmosd 26 vaccines received bnt162b2pfizerbiontech 42 patients mrna1273moderna 14 patients six patients history sarscov2 infection two experienced postinfection disease relapse mogad frequency relapses within one month sarscov2 vaccination 4 1 26 aqp4igg+nmosd group 0 mogad group patients potential benefits vaccination overcome risk relapsespmid35216793 doi101016 jmsard2021103424,0.0
saltinducible kinases inhibitor hg99101 targets ripk3 kinase activity alleviate necroptosismediated inflammatory injury cell death dis 2022 feb 25 13 2 188 doi 101038 s4141902204633yabstractreceptorinteracting protein kinase 3 ripk3 functions central regulator necroptosis mediating signaling transduction activate pseudokinase mixed lineage kinase domainlike protein mlkl phosphorylation increasing evidences show ripk3 contributes pathologies inflammatory diseases including multiple sclerosis infection colitis identified novel small molecular compound saltinducible kinases siks inhibitor hg99101 inhibiting necroptosis targeting ripk3 kinase activity found siks inhibitor hg99101 block tnf tolllike receptors tlrs mediated necroptosis independent siks revealed hg99101 dramatically decreased cellular activation ripk3 mlkl meanwhile hg99101 inhibited association ripk3 mlkl oligomerization downstream mlkl interestingly found hg99101 also trigger ripk3ripk1caspase 1caspase 8dependent apoptosis activated cleavage gsdme leading dependent pyroptosis mechanistic studies revealed siks inhibitor hg99101 directly inhibited ripk3 kinase activity block necroptosis interacted ripk3 recruited ripk1 activate caspases leading cleave gsdme importantly mice pretreated hg99101 showed resistance tnfinduced systemic inflammatory response syndrome consistently hg99101 treatment protected mice staphylococcus aureusmediated lung damage targeting ripk3 kinase activity overall results revealed siks inhibitor hg99101 novel inhibitor ripk3 kinase potential therapeutic target treatment necroptosismediated inflammatory diseasespmid35217652 doi101038 s4141902204633y,0.0
microglia therapeutic targets central nervous system remyelination curr opin pharmacol 2022 feb 23 63102188 doi 101016 jcoph2022102188 online ahead printabstractfailed remyelination underpins neurodegeneration central nervous system cns dysfunction aging progression neurological diseases multiple sclerosis alzheimers disease existing therapies shown limited efficacy halting disease progression humans highlighting need identify proremyelination treatments microglia cnsresident macrophages critical roles regulation remyelination representing promising therapeutic target however currently therapeutics specifically target microglia recent studies revealed microglia heterogenous population distinct transcriptional states health disease conditions including remyelination suggesting functional differences states discuss potential contributions different microglia states degenerative regenerative processes examine potential target microglia statespecific manner promote remyelination consider key issues addressed therapies can clinically appliedpmid35219055 doi101016 jcoph2022102188,1.0
effects continuous care model using smartphone application adherence treatment selfefficacy among patients multiple sclerosis background adherence diseasemodifying therapy important patients multiple sclerosis ms increase positive outcomes improve quality life study aimed determine effects continuous care model ccm using smartphone application adherence treatment selfefficacy among ms patientsmethodsthis quasiexperimental study pre posttest design conducted 72 ms patients shiraz iran june 2020 august 2021 samples randomly assigned intervention n 36 control n 36 groups intervention group ccm using smartphone application implemented two months however intervention performed control group data collected using selfreport multiple sclerosis treatment adherence questionnaire mstaq ms selfefficacy scale msss baseline two four months interventionresultsthe results showed improvement adherence treatment selfefficacy intervention group compared control group implementing virtual ccm twomonth followup p 0001 conclusionsimplementing ccm using smartphone application resulted improvements ms patients adherence treatment selfefficacy can concluded providing care using interactive multimedia application can improve outcomes well patients satisfaction especially covid19 pandemic therefore approach recommended used nurses healthcare providers clinicians,0.0
randomized feasibility trial scleroderma patientcentered intervention network selfmanagement spinself program background scleroderma patientcentered intervention network spin developed online selfmanagement program spinself designed improve diseasemanagement selfefficacy people systemic sclerosis ssc scleroderma aim study evaluate feasibility aspects conducting fullscale randomized controlled trial rct spinself programmethodsthis feasibility trial embedded spin cohort utilized cohort multiple rct design design time cohort enrollment cohort participants consent assessed trial eligibility randomized prior informed trial participants intervention arm informed provide consent control group forty englishspeaking spin cohort participants canada usa uk low diseasemanagement selfefficacy selfefficacy managing chronic disease scale semcd score 7 interested using online selfmanagement program randomized 32 ratio offered spinself program usual care 3 months program usage examined via automated usage logs user satisfaction assessed semistructured interviews trial personnel time requirements implementation challenges loggedresultsof 40 spin cohort participants randomized 26 allocated spinself 14 usual care automated eligibility randomization procedures via spin cohort platform functioned properly except two participants semcd scores 7 scores 72 73 respectively included caused system programming error rounded semcd scores 26 spin cohort participants offered spinself program 9 35 consented use program usage logs showed use spinself program low 2 9 users 22 logged program median 3 4 9 44 accessed none 1 9 programs modules median 2 conclusionsthe results study will lead substantial changes planned fullscale rct spinself program will incorporate planned additional feasibility trial progression fullscale trial changes include transitioning conventional rct design prerandomization consent supplementing online selfhelp peerfacilitated videoconferencebased groups enhance engagementtrial registrationclinicaltrialsgov nct03914781 registered 16 april 2019,0.0
factors associated switching injectable oral disease modifying agents among patients multiple sclerosis abstractbackground since introduction oral diseasemodifying agents dma 2010 treatment options multiple sclerosis ms changed significantly limited information regarding factors associated switching oral dma among prevalent injectable dma usersobjective study evaluated factors associated switching oral dmas among prevalent injectable dma users msmethods retrospective observational cohort study using trinetx electronic medical records emr data conducted among patients ms study included prevalent injectable dma users least two injectable dma interferon beta1a interferon beta1b peginterferon beta1a glatiramer acetate prescribing records within 6 months september 2010 may 2018 second injectable dma prescription date considered index date switching defined oral dma prescription record fingolimod dimethyl fumarate teriflunomide within 12 months index date patients infusion dma prescription first injectable dma prescription less 18 years age excluded study andersen behavioral model conceptual framework used identify predisposing enabling need factors measured 1year baseline period index date multivariable logistic regression model used examine predisposing age sex race ethnicity enabling timeperiod need factors comorbidities ms symptoms msrelated medication healthcare utilization associated switching injectable oral dmasresults among 2 943 prevalent injectable users included study 809 n238 patients switched oral dmas patients switched oral dmas primarily younger adults aged 1844 years 6429 females 8277 sensory visual symptoms corticosteroid utilization oneyear lookback period compared nonswitchers results multivariable logistic regression model revealed middleaged adults 4564 years adjusted odds ratio aor 043 95 confidence interval ci 032058 old adults 65 years aor 030 95 ci 013066 men aor 067 95 ci 047096 associated decreased odds switching oral dmas presence msrelated sensory symptoms aor 152 95 ci 107216 visual symptoms aor 159 95 ci 110231 corticosteroids usage aor 144 95 ci 104198 associated increased odds switching oral dmasconclusion study found one twelve prevalent injectable dma users switched oral dma demographic clinical factors associated switching oral dmas research needed evaluate outcomes switching inform treatment decisions ms management,0.0
acupuncture multiple sclerosis literature review abstractbackground acupuncture complementary alternative medicine cam modality appears helpful integrative therapy multiple sclerosis ms due chronicity disease persistent symptoms large number patients seek use cam ms treatment therefore present review aimed determine effectiveness acupuncture treatment multiple sclerosismethods pubmed database searched english articles least english abstracts september 2021 including articles published since earliest literature september 2021 review articles searched relevant data searched keywords titles abstracts included acupuncture electroacupuncture multiple sclerosis results totally 75 studied articles 31 included research advantages acupuncture mainly reflected regulating neuroimmune system improving quality life reducing fatigue improving bladder function reducing spasm pain limbs delaying progression disease reducing relapsesconclusions according review recent articles traditional chinese acupuncture scalp acupuncture appear help improve symptoms multiple sclerosis including fatigue neural functional deficits pain gait impairments bladder dysfunction reduce relapses therefore acupuncture used integrative therapy patients ms,0.0
pointofcare diagnostic test aquaporin4 antibody seropositive neuromyelitis optica abstractbackgroundgiven need specialized laboratory techniques diagnostic testing serum antibodies aquaporin4 protein associated neuromyelitis optica spectrum disorder nmosd globally accessible aimed evaluate novel pointofcare filter paperbased test serum aqp4 antibodies aqp4ab methodsadults aqp4ab seropositive nmosd seronegative controls central nervous system demyelinating diagnoses used lancets place blood drops 1ml filter paper cards samples analyzed average 94 days using transfected aqp4gfp hek293 cells results compared participantsnull prior serum aqp4ab test results blinded laboratory staffresultsof 40 participants mean age 537 years 83 female 25 cases 15 controls common diagnosis controls multiple sclerosis 73 average nmosd disease duration 63 years aqp4ab seropositive participants disease modifying therapies time participation pointofcare test yielded sensitivity 80 specificity 93 positive negative predictive values 95 74 conclusionthis pointofcare aqp4ab testing method may become pragmatic option diagnose aqp4ab seropositive nmosd difficulttoreach settings method confirmed testing parameters field tested new populations,1.0
study progress recreational activities loneliness young adult carers national student survey background young adults 1825 years informal care responsibilities received limited attention research literature little known caring responsibilities related functioning across different life domains present study examine associations care responsibilities study progress recreational life loneliness young adults higher educationmethodsa national survey conducted among norwegian students higher education shot2018study response rate 308 current sample subsample respondents including young adults 18 25 years old comprising 40205 participants 702 women mean age 220 years sd 17 participants reported whether regular care responsibility someone physical mental illness disabilities substance misuse also answered questions study progress number hours studying physical exercise involvement organized volunteer student activities number close friends feelings loneliness data analyzed chisquare tests logistic regression analyses adjusting age sex chronic illnessresultscompared students without care responsibility young adult carers n 2228 55 study sample likely report delayed study progress 120 p 001 higher average number failed exams eg failed three times 131 p 002 feelings loneliness 126 p 001 slightly fewer friends limited care responsibility 1 h daily likely participate organized volunteer student activities whereas students 2 h caring per day less likely participate leisure student activities study progress feelings loneliness related care responsibility responsedose pattern worse outcomes 2 h daily caring responsibility comparisons adjusted age sex chronic illnessconclusionsstudy progress recreational activities loneliness among young adults associated informal caring responsibilities professionals educational system well health personnel sensitized needs young adult carers necessary support made available,0.0
selective inhibitor nlrp3 inflammasome potential therapeutic approach neuroprotection transgenic mouse model huntingtons disease background huntingtons disease hd neurodegenerative disorder caused expansion cag repeat huntingtin htt gene number cag repeats exceeds 36 translated expanded polyglutaminecontaining htt protein mutant htt mhtt interferes normal functions many cellular proteins subsequently jeopardizes important cellular machineries major types brain cells including neurons astrocytes microglia nacht lrr pyd domaincontaining protein 3 nlrp3 inflammasome comprises nlrp3 asc caspase1 involved activation il1 il18 implicated various biological functions although existence nlrp3 inflammasome brain documented roles nlrp3 inflammasome hd remain largely uncharacterized mcc950 highly selective potent smallmolecule inhibitor nlrp3 used treatment several diseases alzheimers disease however whether mcc950 also beneficial hd remains unknown therefore hypothesized mcc950 exerts beneficial effects transgenic mouse model hdmethodsto evaluate effects mcc950 hd used r6 2 b6cbatg hdexon1 62gpb 1j transgenic mouse model hd expresses exon 1 human htt gene carrying 120 5 cag repeats male transgenic r6 2 mice treated daily mcc950 10 mg kg body weight oral administration water 5 weeks age 7 weeks examined neuronal density neuroinflammation mhtt aggregation striatum r6 2 mice vs wildtype littermates also evaluated motor function body weight lifespan r6 2 miceresultssystematic administration mcc950 r6 2 mice suppressed nlrp3 inflammasome decreased il1 reactive oxygen species production reduced neuronal toxicity assessed based increased neuronal density upregulation neun psd95 proteins importantly oral administration mcc950 increased neuronal survival reduced neuroinflammation extended lifespan improved motor dysfunction r6 2 miceconclusionscollectively findings indicate mcc950 exerts beneficial effects transgenic mouse model hd therapeutic potential treatment devastating neurodegenerative disease,0.0
plasma protein levels analysis multiple sclerosis sardinian families identified c9 cyp24a1 candidate biomarkers life basel 2022 jan 20 12 2 151 doi 103390 life12020151abstracthere investigate protein levels 69 multiple sclerosis ms cases 143 healthy controls hc twenty sardinian families search promising biomarkers plasma using antibody suspension bead array technology plasma levels 56 msrelated proteins obtained differences ms cases hc estimated using linear mixed models linear quantile mixed models proportion proteins level variability explained set 119 msrisk snps literature also quantified higher plasma c9 cyp24a1 levels found ms cases compared hc p 005 holm multiple testing correction protein level differences estimated respectively 053 95 ci 025 081 042 95 ci 019 065 times plasma level standard deviation measured hc furthermore c9 resulted statistically significantly higher relapsingremitting ms rrms secondaryprogressive ms spms compared hc spms showing highest differences instead cyp24a1 statistically significantly higher rrms compared hc respectively 26 95 ci 10 44 16 95 ci 9 39 cyp24a1 c9 plasma level variability explained known msrisk snps results highlight c9 cyp24a1 potential biomarkers plasma ms allow us gain insight molecular disease mechanismspmid35207439 doi103390 life12020151,0.0
vincamine modulates effect pantoprazole renal ischemia#x2f reperfusion injury attenuating mapk apoptosis signaling pathways molecules 2022 feb 18 27 4 1383 doi 103390 molecules27041383abstractpantoprazole antioxidant function reactive oxygen species ros vincamine herbal candidate indole alkaloid clinical use brain sclerosis aim present experiment evaluate molecular level first time value vincamine addition pantoprazole treating experimentally induced renal ischemia reperfusion injury iri onehundredandtwentyeight healthy male wistar albino rats included serum creatinine blood urea nitrogen malondialdehyde levels assessed elisa used estimate proinflammatory cytokines expression bcl2 bax genes assessed quantitative realtime pcr erk1 2 jnk1 2 p38 cleaved caspase3 nfb proteins expressions estimated using western blot assay kidneys also histopathologically studied iri resulted impaired cellular functions increased creatinine urea nitrogen malondialdehyde tnf il6 il1 serum levels upregulated nfb jnk1 2 erk1 2 p38 cleaved caspase3 proteins furthermore downregulated expression bcl2 gene upregulated bax gene treatment vincamine addition pantoprazole multiple doses significantly alleviated biochemical histopathological changes pantoprazole vincamine alone whether dose single multiple declaring synergistic effect conclusion vincamine pantoprazole multiple doses mitigated renal iri inhibition apoptosis attenuation extracellular signaling pathways proinflammatory cytokines levels suppression mapk erk1 2 jnk p38 nfb intracellular signaling pathwaypmid35209172 doi103390 molecules27041383,0.0
multimodal evoked potentials potential biomarkers disease activity patients clinically isolated syndrome front neurol 2022 feb 8 12678035 doi 103389 fneur2021678035 ecollection 2021abstractobjective ongoing search markers useful monitoring predicting disease activity early stage multiple sclerosis ms goals study prospectively evaluate changes parameters multimodal evoked potentials ep cognition within 3year followup period patients clinically isolated syndrome cis assess prognostic value baseline findings regard disease outcomesmethods 29 patients 20 women nine men mean age 311 multimodal visual brainstem auditory somatosensory eventrelated ep neuropsychological tests nt performed baseline t0 1 t1 3 t3 years results compared longitudinally baseline t1 t3 baseline results confirmed conversion cis multiple sclerosis ms disability level t1 t3 using multiple comparisons logistic regression modelresults apart mean n13 p16 sep somatosensory evoked potentials amplitude lower t1 t3 baseline t0 102 037 v t1 090 026 v t3 074 032 v p 005 comparisons significant changes ep nt parameters found longitudinal assessment baseline p300 pz latency longer patients ms cis t1 35269 vs 32556 ms predictive value shown analyzed baseline variables regard conversion cis mssignificance baseline erp abnormalities associated shortterm conversion ms erp worth considering multimodal ep evaluation early stage mspmid35211070 pmcpmc8860823 doi103389 fneur2021678035,0.0
quantification neurite degeneration enhanced accuracy efficiency vitro model parkinson#39 s disease eneuro 2022 feb 22eneuro0327212022 doi 101523 eneuro0327212022 online ahead printabstractneurite degeneration associated early stages neurodegenerative disorders alzheimers disease parkinsons disease pd amyotrophic lateral sclerosis one method commonly used analyze neurite degeneration involves calculation degeneration index di following utilization analyze particles tool imagej detect neurite fragments micrographs cultured cells however di analyses prone several types measurement error can time consuming perform limited application describe improved method performing di analyses accuracy measurements enhanced modification selection criteria detecting neurite fragments removal image artifacts nonneurite materials images optimization image contrast enhancements implemented imagej macro enables rapid fully automated di analysis multiple images macro features operations automated removal cell bodies micrographs thus expanding application di analyses use experiments involving dissociated cultures present experimental findings supporting compared conventional method enhanced analysis method yields measurements increased accuracy requires significantly less time perform furthermore demonstrate utility method investigate neurite degeneration cell culture model pd conducting experiment revealing effects cjun nterminal kinase jnk neurite degeneration induced oxidative stress human mesencephalic cells improved analysis method may used gain novel insight factors underlying neurite degeneration progression neurodegenerative disorderssignificance statementneurite degeneration cellular event associated early stages multiple types neurodegenerative disorders molecular factors regulate neurite degeneration remain poorly understood existing methods studying neurite degeneration limited application efficiency identify modifications widely used procedure analyzing neurite degeneration reduce measurement error methodological enhancements incorporated imagej macro thereby facilitating rapid completely automated analysis neurite degeneration using large sets micrographs using cell culture model parkinsons disease pd demonstrate macro facilitates accurate efficient neurite degeneration measurements expanding suitability analysis method experiments involving dissociated culturespmid35210286 doi101523 eneuro0327212022,0.0
newly diagnosed multiple sclerosis patient ocular myasthenia gravis case report medicine baltimore 2022 feb 25 101 8 e28887 doi 101097 md0000000000028887abstractrationale patients myasthenia gravis may also comorbid autoimmune diseases since myasthenia gravis neuromyelitis optica spectrum disease mediated antibodies likely occur together however since multiple sclerosis autoimmune disease mediated specific antibody fewer immune mechanisms common myasthenia gravis neuromyelitis optica spectrum disease encountered case newly developed multiple sclerosis patient myasthenia gravispatient concerns 46yearold man diagnosed ocular myasthenia gravis 6 years ago taking pyridostigmine control symptomsdiagnosis patient developed right optic neuritis multiple sclerosis suspected based brain magnetic resonance imaging findings however required diagnostic criteria metinterventions diseasemodifying therapy initiated clinical progression disease monitoredoutcomes one year onset optic neuritis patient developed myelitis diagnosed multiple sclerosis prompting treatment diseasemodifying therapylessons optic neuritis occurs patients myasthenia gravis careful evaluation necessary considering possibility may first symptom demyelinating central nervous system disease therefore important conduct shorterinterval monitoring symptom screening patients neurological autoimmune diseases myasthenia gravis even multiple sclerosis initially suspected achieve early detection multiple sclerosispmid35212290 doi101097 md0000000000028887,1.0
successful treatment tocilizumab refractory anemia slowly progressive renal glomerulosclerosis multicentric castleman disease case report medicine baltimore 2022 feb 25 101 8 e28941 doi 101097 md0000000000028941abstractrationale multicentric castleman disease mcd rare lymphoproliferative disorder accompanied systemic symptoms characterized polyclonal hypergammaglobulinemia chronic inflammation due overexpression interleukin6 histological heterogeneity renal involvement mcd described although number reports limited tocilizumab humanized antiinterleukin6 receptor antibody reported effective mcdpatent concerns 64yearold man experienced refractory anemia slowly progressive renal dysfunction proteinuria accompanied persistent inflammation 11 yearsdiagnosis two renal biopsies obtained first biopsy performed 7 years admission revealed nonspecific interstitial inflammation whereas second biopsy demonstrated global sclerosis glomeruli interstitial fibrosis patient multiple lymphadenopathies cervical lymph node biopsy histological findings compatible plasma cell type castleman disease patient evidence human hepatitis virus8 infectionintervention patient treated 60 mg d prednisolone followed 8 mg kg intravenous tocilizumab every 2 weeksoutcome anemia significantly improved well marked reduction proteinuria stabilization renal function experience renal function 2years followup periodlessons heterogeneity renal manifestations mcd sometimes makes early diagnosis difficult need interpret histological findings renal biopsy carefully advancedstage renal diseases tocilizumab might effective treatment strategy mcdpmid35212301 doi101097 md0000000000028941,0.0
increased complement activation systemic sclerosis patients skin lung fibrosis j pers med 2022 feb 15 12 2 284 doi 103390 jpm12020284abstractintroduction involvement complement system phenotypic expression systemic sclerosis ssc debated topic aimed assay complement fractions ssc patients correlate levels clinical course diseasekey points 1 ch50 increased ssc patients compared hc 2 serum c2 levels increased ssc patients compared hc 3 ch50 may represent biomarker skin lung fibrosis severity ssc patientsmethod complement hemolysis 50 ch50 c2 c3 c4 levels assessed 85 ssc patients 47 healthy controls hc results ssc patients displayed statistically significant higher value ch50 763 u ml iqr 658894 u ml vs 296 u ml iqr 24734 u ml p 00001 c2 261 mg l iqr 241321 mg l vs 227 mg l iqr 206244 mg l p 00001 compared hc patients diffuse cutaneous ssc dcssc higher levels ch50 patients limited cutaneous ssc lcssc 836 u ml iqr 7231027 u ml vs 713 u ml iqr 637836 u ml p 0003 ssc patients interstitial lung disease ild higher ch50 levels compared ssc patients without ild 796 u ml iqr 683974 u ml vs 697 u ml 546857 u ml p 0042 positive linear correlation existed ch50 modified rodnan skin score mrss r 0285 p 0008 disease severity scale dss r 0285 p 0005 negative linear correlation demonstrated ch50 diffusing capacity carbon monoxide dlco r 0252 p 0012 multiple linear regression analysis dss significant p 001 beta coefficient 2446 conclusions results show increment ch50 serum c2 levels ssc patients comparison hc retain ch50 may represent biomarker disease severity skin lung fibrosis patientspmid35207772 doi103390 jpm12020284,0.0
acidsensing ion channels glial cells membranes basel 2022 jan 20 12 2 119 doi 103390 membranes12020119abstractacidsensing ion channels asics protongated cation channels key mediators responses neuronal injury asics exhibit unique patterns distribution brain high expression neurons low expression glial cells lot focus asic neurons less known roles asics glial cells asic1a expressed astrocytes might contribute synaptic transmission longterm potentiation oligodendrocytes constitutive activation asic1a participates demyelinating diseases asic1a asic2a asic3 found microglial cells mediate inflammatory response pathological conditions asic dysregulation glial cells can contribute disease states example activation astrocytic asic1a may worsen neurodegeneration glioma staging activation microglial asic1a asic2a may perpetuate ischemia inflammation oligodendrocytic asic1a might involved multiple sclerosis review concentrates unique asic components glial cells integrates glialspecific asics physiological pathological conditions knowledge provides promising evidence targeting asics individual glial cells therapeutic strategy diverse range conditionspmid35207041 doi103390 membranes12020119,1.0
neurology#39 s vital role preventing unnecessary potentially harmful pediatric studies expert rev neurother 2022 feb 25 doi 101080 1473717520222045953 online ahead printabstractintroduction regulatory authorities recognize two human populations adults children defined 18 years drug approval demand separate studies humans mature slowly puberty 18th birthday administrative limit correspond physiological change separate drug approval 18th birthday reflects childrenaretherapeuticorphans concept emerged 1962 food drug administration fda backed away concept antiepileptic drugs sticks areas contrast european medicines agency ema continuously expanding demand pediatric studies parents hesitate increasingly let children participate questionable studiesareas covered neurologists challenge childrenaretherapeuticorphans mantra young patients need separate proof efficacy safety appropriate dosing recommendations minors treated human beings instead abused questionable studiesexpert opinion young patients multiple sclerosis neurological diseases deserve studies therapeutic intentions pediatric careers emerged academia regulatory authorities pharmaceutical companies institutional review boards ethics committees suspend questionable pediatric studies reject newly submitted ones medical professions distance questionable pediatric research reflects massive conflicts interestpmid35213279 doi101080 1473717520222045953,0.0
efficacy safety outcomes diroximel fumarate switching prior therapies continuing drf results phase3 evolvems1 study adv ther 2022 feb 24 doi 101007 s12325022020687 online ahead printabstractintroduction diroximel fumarate drf oral fumarate relapsing multiple sclerosis ms active metabolite dimethyl fumarate dmf drf safety efficacy profile similar dmf improved gastrointestinal gi tolerability low 1 treatment discontinuation due gi adverse events aes efficacy safety outcomes patients switched drf diseasemodifying therapies dmts evaluatedmethods evolvems1 ongoing 2year openlabel phase 3 study drf adults relapsingremitting ms patients either entered newly enrolled drf trials 5week randomized headtohead phase 3 evolvems2 study drf dmf analysis evaluated safety gi tolerability patients continuing drf drfrollover switching dmf dmfrollover following evolvems2 safety efficacy evaluated subset newly enrolled patients received prior glatiramer acetate ga ga drf interferons ifn ifn drf recent dmt prior switching drf evolvems1results september 1 2020 1057 patients enrolled evolvems1 including 166 182 239 225 patients ga drf ifn drf drfrollover dmfrollover groups respectively treatment discontinuation due gi aes 1 groups ga drf ifn drf patients experienced improvements baseline clinical radiological efficacy outcomes including significantly reduced annualized relapse rates rollover patients low rates new recurrent gi aes drfrollover 268 42 dmfrollover 271 49 conclusion 2 years drf exposure patients prior ga ifn fumarate treatment safety outcomes consistent previous fumarate studies efficacy patients prior ga ifn treatment consistent previous fumarate studies data suggest transition drf ga ifn dmf reasonable treatment strategy low rates discontinuation due gi aestrial registration clinicaltrialsgov nct02634307 infographicpmid35211872 doi101007 s12325022020687,0.0
tdp43 proteinopathy causes broad metabolic alterations including tca cycle intermediates dopamine levels drosophila models als metabolites 2022 jan 21 12 2 101 doi 103390 metabo12020101abstractamyotrophic lateral sclerosis als fatal complex neurodegenerative disorder causes selective degeneration motor neurons als patients exhibit symptoms consistent altered cellular energetics hypermetabolism weight loss dyslipidemia insulin resistance altered glucose tolerance although evidence supports metabolic changes als patients metabolic alterations cellular level remain poorly understood used drosophila model als based tdp43 expression motor neurons recapitulates hallmark features motor neuron disease including tdp43 aggregation locomotor dysfunction reduced lifespan gain insights metabolic changes caused tdp43 performed global metabolomic profiling larvae expressing tdp43 wt als associated mutant variant g298s identified significant alterations several metabolic pathways report alterations multiple metabolic pathways highlight upregulation tricarboxylic acid tca cycle metabolites defects neurotransmitter levels also show modulating tca cycle flux either genetically dietary intervention mitigates tdp43dependent locomotor defects addition dopamine levels significantly reduced context tdp43g298s find treatment pramipexole dopamine agonist improves locomotor function vivo drosophila models tdp43 proteinopathypmid35208176 doi103390 metabo12020101,0.0
autologous hematopoietic stem cell transplantation multiple sclerosis patients monocentric case series systematic review literature j clin med 2022 feb 11 11 4 942 doi 103390 jcm11040942abstractmultiple sclerosis ms chronic inflammatory immunemediated disease central nervous system cns commonly affecting young adults potentially associated lifelong disability 14 diseasemodifying treatments dmts currently approved treatment ms however despite use highly effective therapies patients exhibit highly active disease aggressive course onset higher risk longterm disability accrual last years several retrospective studies clinical trials metaanalyses systematic reviews investigated autologous hematopoietic stem cell transplantation ahsct possible therapeutic option order address unmet clinical need studies demonstrated ahsct highly efficacious relatively safe therapeutic option treatment highly active ms particularly recent years amount evidence grown significant improvements development patient selection criteria choice suitable transplant technique clinical experience paper present six patients received ahsct ms center systematically reviewed recent evidence longterm efficacy safety ahsct placement ahsct rapidly evolving therapeutic armamentarium mspmid35207216 doi103390 jcm11040942,0.0
painrelated coping behavior als interplay maladaptive coping patient#39 s affective state pain j clin med 2022 feb 11 11 4 944 doi 103390 jcm11040944abstractbackground pain common symptom patients amyotrophic lateral sclerosis als coping plays central role adjustment painobjective study evaluates use different pain coping strategies patients als investigates interplay maladaptive coping patients affective state painmethods one hundred fifty als patients three german outpatient clinics completed brief pain inventory bpi alsfunctional rating scaleextension alsfrsex als depression inventory adi12 subscale emotional functioning als assessment questionnaire alsaq40 coping strategies questionnaire csq based upon results correlational analyses multiple regression analyses performed identify predictors pain severity explore factors contributing maladaptive copingresults pain prevalent 56 n 84 patients patients applied different adaptive coping strategies well maladaptive strategy catastrophizing regression analysis indicated csqsubscale catastrophizing significantly predicted pain intensity explaining 340 variance p 0001 painrelated catastrophizing associated higher painrelated functional impairments worse emotional functioning adi12 sum score indicator depressive symptoms contributed significantly maladaptive coping strategy catastrophizing p 0001 explained 408 varianceconclusion patients als apply different strategies cope pain catastrophizing important determinant higher pain intensity ratings associated higher pain interferences decreased emotional wellbeing painrelated catastrophizing promoted depressive symptoms catastrophizing depressive symptoms thus represent important targets individualized painmanagement strategiespmid35207215 doi103390 jcm11040944,0.0
final frontier environmentgenome interactions integrated multiomic approaches predictions noncommunicable disease risk front genet 2022 feb 8 13831866 doi 103389 fgene2022831866 ecollection 2022abstractepidemiological associative research humans animals identifies correlations environment health impacts environmenthealth interrelationship effected individuals underlying genetic variation mediated mechanisms include changes gene regulation associated diversity phenotypes exhibit however causal relationships yet established part associations reduced individual interactions combinatorial effects rarely studied problem exacerbated fact genomes highly dynamic integrate information across multiple levels linear sequence structural organisation temporal variation open responds environmental influence unravel complexities genomic basis human disease particular noncommunicable diseases also influenced environment eg obesity type ii diabetes cancer multiple sclerosis neurodegenerative diseases inflammatory bowel disease rheumatoid arthritis imperative fully integrate multiple layers genomic data review current progress integrated genomic data analysis discuss cases data integration lead significant advances ability predict environment may impact health also outline limitations form basis future research questions review will lay foundations future research impact environment healthpmid35211161 pmcpmc8861380 doi103389 fgene2022831866,0.0
muscle quality knee extensors based several types force multiple sclerosis patients varying degrees disability medicina kaunas 2022 feb 19 58 2 316 doi 103390 medicina58020316abstractbackground objectives multiple sclerosis ms tends affect muscle performance mainly lower extremities degree disability associated loss strength muscle mass varying extents muscle quality mq expresses amount force produced relative activated muscle mass purpose study compare mq knee extensors main manifestations strength isometric dynamic strength power among patients differing degrees neurological disability evolutionary forms disease also establish reference values mq ms patients pwms materials methods total 250 pwms evaluated according expanded disability status scale edss maximum dynamic isometric forces muscle power manifested load 60 maximum dynamics knee extensors lean mass thigh hip determined densitometry mq calculated three types force evaluated results pwms relapsing remitting ms rrms presented isometric mq values 158 better pwms primary progressive ms ppms 138 better pwms secondary progressive ms spms pwms spms dynamic mq 167 worse patients rrms power mq 295 worse degree disability 4 75 edss score patients better mq mild edss scores patients severe edss scores 248 259 403 worse isometric dynamic power mq scores respectively rrms based results reference values mq pwms established conclusions pwms different types ms show differences lean mass strength show differences mq pwms different edss grades differences lean mass differences strength based mq especially power mqpmid35208639 doi103390 medicina58020316,0.0
astrocytes inflammatory t helper cells dangerous liaison multiple sclerosis front immunol 2022 feb 8 13824411 doi 103389 fimmu2022824411 ecollection 2022abstractmultiple sclerosis ms neurodegenerative autoimmune disorder central nervous system cns characterized recruitment selfreactive t lymphocytes mainly inflammatory t helper th cell subsets recruited within cns inflammatory th cells produce several inflammatory cytokines chemokines activate resident glial cells thus contributing breakdown bloodbrain barrier bbb demyelination axonal loss astrocytes recognized key players ms immunopathology respond th celldefining cytokines acquiring reactive phenotype amplify neuroinflammation cns contribute ms progression review summarize current knowledge astrocytic changes behaviour ms experimental autoimmune encephalomyelitis eae contribution pathogenic th1 th17 th1like th17 cell subsets cd8+ t cells morphological functional modifications occurring astrocytes pathological outcomespmid35211120 pmcpmc8860818 doi103389 fimmu2022824411,1.0
predicting multiple sclerosis challenges opportunities front neurol 2022 feb 8 12761973 doi 103389 fneur2021761973 ecollection 2021abstractdetermining effective means preventing multiple sclerosis ms relies testing preventive strategies trial populations however low incidence ms demonstrating preventive measure benefit requires either large trial populations enriched population higher disease incidence risk scores incorporate genetic environmental data used principle identify highrisk individuals enrolment preventive trials discuss concepts developing predictive scores identifying individuals high risk ms discuss empirical efforts using real cohorts challengesboth theoretical practicallimiting work argue scores offer means risk stratification preventive trial design unlikely ever constitute clinicallyhelpful approach predicting ms individualpmid35211072 pmcpmc8860835 doi103389 fneur2021761973,0.0
wsdtnbi novel networkbased inference method virtual screening chem sci 2021 dec 21 13 4 10601079 doi 101039 d1sc05613a ecollection 2022 jan 26abstractin recent years rapid development networkbased methods prediction drugtarget interactions dtis provides opportunity emergence new type virtual screening vs namely networkbased vs herein reported novel networkbased inference method named wsdtnbi compared previous networkbased methods use unweighted dti networks wsdtnbi uses weighted dti networks whose edge weights correlated binding affinities twopronged approach based weighted dti drugsubstructure association networks employed calculate prediction scores show practical value wsdtnbi performed networkbased vs retinoidrelated orphan receptor t rort purchased 72 compounds experimental validation seven purchased compounds confirmed novel rort inverse agonists vitro experiments including ursonic acid oleanonic acid ic50 values 10 nm 028 m respectively moreover direct contact ursonic acid rort confirmed using xray crystal structure vivo experiments demonstrated ursonic acid oleanonic acid therapeutic effects multiple sclerosis results indicate wsdtnbi might powerful tool networkbased vs drug discoverypmid35211272 pmcpmc8790893 doi101039 d1sc05613a,0.0
impact diseasemodifying therapies humoral cellular immuneresponses following sarscov2 vaccination ms patients clin transl sci 2022 feb 25 doi 101111 cts13256 online ahead printabstractthe impact distinct diseasemodifying therapies dmts sarscov2 vaccination efficacy multiple sclerosis ms patients still enigmatic prospective comparative study investigated humoral cellular immuneresponses ms patients receiving interferon beta natalizumab ocrelizumab prevaccination 6 weeks post 2nd sarscov2 vaccination healthy individuals interferon beta treated patients generated robust humoral cellular immuneresponses humoral immune responses diminished ocrelizumab treated patients cellular immuneresponses reduced natalizumab treated patients thus humoral cellular immuneresponses closely monitored patients dmts patients poor cellular immuneresponse may benefit additional vaccination cycles patients diminished humoral immuneresponse may benefit treatment sarscov2 antibodies case infectionpmid35213793 doi101111 cts13256,0.0
omicronspecific cytotoxic tcell responses third dose mrna covid19 vaccine among patients multiple sclerosis treated ocrelizumab jama neurol 2022 feb 25 doi 101001 jamaneurol20220245 online ahead printabstractimportance sarscov2 variant b11529 omicron escapes neutralizing antibodies elicited covid19 vaccination tcell responses might better conserved crucial assess third vaccination modifies responses particularly immunocompromised patients readily impaired antibody responsesobjective determine tcell responses omicron spike protein anticd20treated patients multiple sclerosis ms third messenger rna covid19 vaccinationdesign setting participants prospective cohort study conducted march 2021 november 2021 university hospital geneva adults ms receiving anticd20 treatment ocrelizumab identified treating neurologists enrolled study total 20 patients received third dose messenger rna covid19 vaccine included analysisinterventions blood sampling 1 month third vaccine dosemain outcomes measures quantification cd4 cd8 cytotoxic t cells specific sarscov2 spike proteins vaccine strain well delta omicron variants comparing frequencies third vaccine doseresults 20 included patients 11 55 male median iqr age 458 378533 years spikespecific cd4 cd8 tcell memory variants maintained 9 12 patients 6 months second vaccination albeit lower median frequencies delta omicron variants compared vaccine strain cd8 t cells delta 830 95 ci 7361145 omicron 789 95 ci 5941000 cd4 t cells delta 722 95 ci 674905 omicron 625 95 ci 510890 third dose enhanced number responders variants 11 15 patients significantly increased cd8 tcell responses frequencies omicronspecific cd8 t cells remained 711 95 ci 416962 responses specific vaccine strainconclusions relevance cohort study patients ms treated ocrelizumab robust tcell responses recognizing spike proteins delta omicron variants suggesting covid19 vaccination patients taking bcelldepleting drugs may protect serious complications covid19 infection tcell response rates increased third dose demonstrating importance booster dose populationpmid35212717 doi101001 jamaneurol20220245,0.0
genomewide dna methylation profiling identifies epigenetic changes cd4+ cd14+ cells multiple sclerosis patients abstractmultiple sclerosis ms chronic autoimmune degenerative disease central nervous system develops genetically predisposed individuals upon exposure environmental influences environmental triggers ms viral infections smoking demonstrated affect dna methylation thus involve important epigenetic mechanism development pathological process identify msassociated dna methylation hallmarks performed genomewide dna methylation profiling two cell populations cd4+ tlymphocytes cd14+ monocytes collected treatmentnaive relapsingremitting ms patients healthy subjects using illumina 450k methylation arrays revealed significant changes dna methylation cell populations ms cd4+ cells ms patients majority differentially methylated positions dmps shown hypomethylated cd14+ cells hypermethylated differential methylation hladrb1 gene cd4+ cd14+ cells associated carriage drb115 allele independently disease status besides 20 identified dmps shared two cell populations direction methylation changes may involved basic epigenetic processes occuring ms findings suggest epigenetic mechanism dna methylation immune cells contributes ms studies now required validate results understand functional significance,0.0
one year follow patients multiple sclerosis covid19 pandemic crosssectional study qom province iran abstractbackgroundin current covid19 pandemic multiple sclerosis ms patients represent population particular interest might higher risk covid19 infection itnulls complications present study aimed investigate one year follow patients ms covid19 pandemic qom province iranmethodsthis study performed ms clinic beheshti hospital june 1 2020 november 1 2021 202 patients diagnosis ms negative selfreported history covid19 beginning pandemic enrolled first demographic characteristics patients collected second patients underwent serological testing antisarscov2 igg antibodies year later revalauted asked occurrence clinical relapse leading hospitalization disease progression dmt profile covid19 vaccination history covid19 infection considered six weeks covid19 regarding relapse occurrence eventually statistical analysis carried using spss 260resultsof 202 patients 26 patients 1287 initially positive index antibody result followup periods 25 patients 1237 infected covid19 mainly mild 748 significantly lower general population 118 patients 5841 vaccinated covid19 reduced risk covid19 development p001 except case myelitis associated vaccination serious adverse event reported additionally one patient developed ms relapse following covid19 infection except clinical relapse p 0001 demographic ms characteristics dmt type associated covid19 terms ms course 12 patients 594 discontinued dmts regardless dmt adverse events treatment failure 41 patients 203 experienced clinical relapse 12 escalated second line dmt 27 patients 134 noted history worsening disability mainly occurred coivd19 infectionconclusionthe present study showed significant lower incidence covid19 infection ms patients except clinical relapse demographic ms characteristics dmt type associated covid19 infection addition covid19 vaccination reduced risk covid19 development prognosis favorable majority ms patients,0.0
rna targets tdp43 one important neurodegeneration nuclear loss cytoplasmic aggregation tdp43 common shared pathological feature frontotemporal dementia ftd amyotrophic lateral sclerosis als motor neuron disease also known lou gehrigs disease 1 tdp43 pathology found 97 als cases approximately 45 ftd cases neurodegenerative diseases alzheimers disease 2 however direct mechanisms tdp43 dysregulation contributes neurodegeneration remain largely elusive tdp43 rnabinding protein multiple roles rna metabolism including transcription splicing transport localization stability target mrnas well microrna biogenesis 3 tdp43 thousands rna targets largely unknown targets directly contribute disease known whether can either manipulated therapeutic targets influence disease progression serve biomarkers tdp43 pathologya key nuclear function tdp43 regulate alternative splicing notably suppress inclusion cryptic exons intronic sequences normally spliced mature mrnas 4 dysregulation may result inclusion new stretch amino acids protein production truncated protein loss fulllength protein nonsensemediated decay nmd mrnas premature termination codons ptcs introduced cryptic exons fig 1 rnaseq analysis human neurons reduced tdp43 expression revealed one downregulated genes stathmin 2 stmn2 encoding axonal growthassociated microtubulestabilizing protein expressed neurons 5 6 downregulation specific human stmn2 conserved rodents 5 6 extent loss fulllength stmn2 function contributes als ftd pathogenesis clinical phenotypes still known nonetheless restoring expression fulllength stmn2 represents novel potential therapeutic approachfig 1figure 1suppression cryptic exon splicing tdp43 one normal functions tdp43 nucleus suppress splicing cryptic exons located introns nuclear depletion tdp43 results inclusion cryptic exons mature mrnas leads production truncated proteins case stmn2 due alternative polya site cryptic exon loss normal expression case unc13a due presence premature termination codon ptc subsequent nonsensemediated decay mrna full size imagein studies identify key functional targets tdp43 may directly contribute disease pathogenesis ma et al 7 brown et al 8 identified novel cryptic exons regulated tdp43 including one unc13a fig 1 ma et al 7 reanalyzed published rnaseq dataset abnormal splicing events dataset obtained separating tdp43positive tdp43negative neuronal nuclei als ftd patient postmortem brains identify transcriptomic changes caused nuclear tdp43 depletion similarly brown et al rnaseq analysis human neurons derived induced pluripotent stem cells ipscs depletion tdp43 crispr inhibition 8 among dozens novel cryptic exons groups identified unc13a one robust misspliced genes brown et al also detected missplicing event another unc13 family member unc13b 8 confirm findings ma et al brown et al used human neuronal cell lines ipscderived neurons reduce tdp43 levels found tdp43 depletion caused inclusion cryptic exon unc13a transcript confirming role tdp43 suppressing cryptic exons effect seems direct tdp43 binding site within intron containing cryptic exon unc13a mrna 7 8 moreover found unc13a rna containing cryptic exon ptc degradation target nmd resulting reduced levels unc13a mrna protein effect distinct aberrant stmn2 mrna undergo nmd cycloheximide treatment instead translated truncated stmn2 due predicted alternative polya site cryptic exon 8 next ma et al brown et al analyzed bulk rna sequencing large set brain samples ftd als patients tdp43 pathology thus named ftdtdp alstdp without tdp43 pathology including ftdfus ftdtau alssod1 named based presence fus tau sod1 pathology unc13a cryptic exon found samples patients tdp43 pathology controls patients without tdp43 pathology thus unc13a cryptic exon specific feature tdp43 proteinopathies researchers also performed situ hybridization probes specific cryptic splicing site unc13a mrna unc13a cryptic exoncontaining rna detected neuronal nuclei tdp43 depletion ftdtdp patient brains neurons nuclear tdp43 patient samples controls groups also found correlation levels unc13a cryptic exon phosphorylated tdp43 patients 7 8 results provide evidence direct link tdp43 pathology unc13a cryptic exon raise possibility exon developed another biomarker majority ftd als casesunc13a mrna interesting target tdp43 previously identified risk factor sporadic als als ftd genomewide association studies gwas 9 since unc13a participates vesicle maturation neurotransmitter release 10 loss activity may compromise neuronal function patients groups found two snps strongly associated disease located either within unc13a cryptic exon intron near cryptic exon addition ma et al identified novel variant also located intron contains cryptic exon risk factor disease groups showed strong correlation diseaseassociated snps abundance cryptic exon patient brains expression minigenes containing disease risk variants cultured cells established direct effect variants increasing cryptic exon inclusion tdp43depleted cells findings support notion disease risk variants promote inclusion cryptic exon upon loss nuclear tdp43 providing mechanistic insight variants associated increased risk als als ftd highlighting key role tdp43 disease pathogenesis 7 8 genetic link unc13a disease blocking splicing cryptic exon unc13a another promising therapeutic approachseveral issues remain addressed since small percentage neurons patient brains show loss nuclear tdp43 end disease extent unc13a cryptic exon contributes disease needs established moreover interactions thousands target mrnas tdp43 affects many aspects rna metabolism thus remains seen whether correcting expression level one target mrna sufficient offer tangible clinical benefits many downstream pathways remain dysfunctional simultaneous blocking cryptic exon splicing multiple key target mrnas tdp43 may offer better chance success nonetheless gwas results strongly suggest contribution unc13a missplicing disease pathogenesis may fact tangible worth pursuing thus two new studies greatly enrich understanding key functions tdp43 suggest another cryptic exon novel target therapy potential biomarker familial sporadic als ftd,0.0
upper cervical cord atrophy independent cervical cord lesion volume early multiple sclerosis twoyear longitudinal study abstractbackgroundupper cervical cord atrophy lesions shown associated disease disability progression already early relapsingremitting multiple sclerosis rrms however longitudinal relationship remains unclearobjectiveto investigate crosssectional longitudinal relation focal t2 cervical cord lesion volume cclv regional global mean upper cervical cord area ucca relations disabilitymethodsover twoyear interval subjects rrms n36 healthy controls hc n16 underwent annual clinical mri examinations ucca cclv obtained c1 c4 level linear mixed model analysis performed investigate relation ucca cclv disability timeresultsucca baseline significantly lower rrms subjects compared hcs p0003 decrease faster time p0144 ucca cclv independent time points cervical levels time lower baseline ucca cclv related worsening upper lower extremities function timeconclusionucca cclv independent crosssectionally longitudinally early ms lower ucca cclv related increasing disability time,0.0
social prescribing covid19 pandemic qualitative study service providers clients experiences background covid19 public health restrictions social distancing selfisolation particularly challenging vulnerable people health conditions complex social needs link worker social prescribing widespread uk elsewhere regarded potential provide support vulnerable people pandemic qualitative study explores accounts existing social prescribing service adapted meet clients needs first wave pandemic clients experienced changesmethodsdata collected deprived urban area north east england via remote interviews clients n 44 link workers n 5 service provider managerial staff n 8 mayseptember 2020 thematic data analysis conductedresultsthe research found service providers quickly adapted remote intervention delivery aiming serve existing clients vulnerable groups service providers experienced improved access existing clients via telephone first months remote delivery cases able engage clients previously attended appointments gp surgeries however link workers also experienced challenges building rapport clients engaging clients aims intervention providing service digitally excluded people limited link worker capacity meant clients experienced variable contact link workers experiencing consistent support highly valued helping manage conditions mental wellbeing limited access linked services also adversely affected clients clients living less affluent circumstances worse health likely experience negative impacts longterm condition found health progress social prescribing hold going backwards sometimes negatively affected healthconclusionssocial prescribing offered valued support pandemic remote support sometimes limited impact clients findings highlight vulnerability social prescribings success linked services disrupted findings also show need done upscaling social prescribing provide support digitally excluded populations,0.0
impact posttraumatic stress quality life fatigue women gulf war illness background gulf war illness gwi chronic multisymptomatic disorder characterized fatigue muscle pain cognitive problems insomnia rashes gastrointestinal issues affecting estimated 30 750 000 returning military veterans 19901991 persian gulf war female veterans deployed combat war report medical symptoms like cognition respiratory troubles twice rate compared nondeployed female veterans era heterogeneity gwi symptom presentation complicates diagnosis well identification effective treatments exacerbated presence comorbidities defining subgroups illness may help alleviate complications one clear grouping along lines gender aim determine women gwi can subdivided distinct subgroups based posttraumatic stress disorder ptsd symptom presentationmethodsveterans diagnosed gwi n 35 healthy sedentary controls n 35 recruited miami veterans affairs medical health center symptoms assessed via rand short form health survey multidimensional fatigue inventory davidson trauma scale hierarchal regression modeling performed measures health fatigue ptsd symptoms covariate followed univariate analyses conducted two separate gwi groups based cutpoint 70 total davidson trauma scale value performing heteroscedastic ttests across measuresresultsbased distinct differences found ptsd symptomology regarding health trauma symptoms two subgroups derived within female gwi veterans hierarchical regression models displayed comorbid effects gwi ptsd conditions measurable impacts quality life fatigue r2 0080672 notable differences mental emotional measures overall cut point analysis indicated poorer quality life greater fatigue within measures women gwi ptsd symptoms comparison women gwi without ptsd symptoms healthy controlsconclusionsour current findings support understanding comorbid symptoms gwi ptsd subsequently result poorer quality life fatigue along establishing possibility varying clinical presentations,0.0
novel mribased quantitative water content atlas human brain neuroimage 2022 feb 21119014 doi 101016 jneuroimage2022119014 online ahead printabstractthe measurement quantitative tissuespecific mr properties eg water content longitudinal relaxation time t1 effective transverse relaxation time t2 using quantitative mri clinical field strength 15 t 3t wellexplored topic however none commonly used standard brain atlases mni jhu provide quantitative information within framework quantitative mri brain work reports development first quantitative brain atlas tissue water content 3t methodology create quantitative atlas vivo brain water content based healthy volunteers presented preliminary practical examples potential applications also shown established methods fast reliable measurement absolute water content used achieve high precision accuracy water content t2 mapped based two different methods intermediatetr twopoint method longtr singlescan method twenty healthy subjects age 253 25 years examined quantitative imaging protocols images normalised mni stereotactic coordinates water content atlases healthy volunteers created method compared regionsofinterest generated help standard mni template water content values averaged across rois compared water content values literature finally order demonstrate strength quantitative mri water content maps patients pathological changes brain due stroke tumour glioblastoma multiple sclerosis voxelwise compared healthy brain water content atlases largely independent method used acquire individual water maps global grey matter white matter water content values methods agreed within 05 feasibility detecting abnormal water content brains patients based comparison healthy brain water content atlas demonstrated summary first quantitative water content brain atlas vivo developed voxelwise assessment pathologyrelated changes brain water content performed results suggest qmri combination water content atlas allows quantitative interpretation changes due disease used disease monitoringpmid35202813 doi101016 jneuroimage2022119014,0.0
haematopoietic stem cell transplantation results extensive remodelling clonal t cell repertoire multiple sclerosis front immunol 2022 feb 7 13798300 doi 103389 fimmu2022798300 ecollection 2022abstractautologous haematopoietic stem cell transplantation ahsct vital therapeutic option patients highly active multiple sclerosis ms rates remission suggest ahsct effective form immunotherapy controlling disease despite evolving understanding biology immune reconstitution following ahsct mechanism ahsct enables sustained disease remission beyond period lymphopenia remains elucidated autoreactive t cells considered central ms pathogenesis analyse t cell reconstitution 36 months following ahsct cohort highly active ms patients longitudinal analysis sorted nave memory t cell clones establish ahsct induces profound changes dominant t cell landscape cd4+ cd8+ memory t cell clones lymphopenia induced homeostatic proliferation followed clonal attrition 19 dominant cd4 p 0025 13 dominant cd8 p 0005 clones pretransplant repertoire detected 36 months recovery thymicallyderived cd4 nave t cell repertoire occurs 12 months ongoing 36 months however diversity nave populations increased baseline suggesting principal mechanism durable remission ms ahsct relates depletion putative autoreactive clones cohort ms patients expressing ms risk allele hla drb11501 public clones probed potential biomarkers disease ahsct appears induce sustained periods disease remission dynamic changes clonal t cell repertoire 36 months posttransplantpmid35197974 pmcpmc8859174 doi103389 fimmu2022798300,0.0
coenzyme q10 effects neurological diseases physiol res 2021 dec 30 70 suppl4 s683s714abstractcoenzyme q10 coq10 lipophilic substituted benzoquinone present animal plant cells endogenously synthetized every cell involved variety cellular processes coq10 obligatory component respiratory chain inner mitochondrial membrane addition presence coq10 cellular membranes blood endogenous lipid antioxidant moreover essential factor uncoupling protein controls permeability transition pore mitochondria also participates extramitochondrial electron transport controls membrane physicochemical properties coq10 effects gene expression might affect overall metabolism primary changes energetic antioxidant functions can explain remedial effects coq10 supplementation safe welltolerated even high doses coq10 cause serious adverse effects humans experimental animals new preparations coq10 less hydrophobic structural derivatives like idebenone mitoq developed increase absorption tissue distribution review aims summarize clinical experimental effects coq10 supplementations neurological diseases migraine parkinsons disease huntingtons disease alzheimers disease amyotrophic lateral sclerosis friedreichs ataxia multiple sclerosis cardiovascular hypertension included central mechanisms controlling blood pressure brainstem rostral ventrolateral medulla hypothalamic paraventricular nucleus conclusion seems reasonable recommend coq10 adjunct conventional therapy cases however sometimes coq10 supplementations efficient animal models diseases human patients eg parkinsons disease rather vague eg friedreichs ataxia amyotrophic lateral sclerosis pmid35199552,0.0
mdivi1 promising drug underlying mechanisms treatment neurodegenerative diseases histol histopathol 2022 feb 2418443 doi 1014670 hh18443 online ahead printabstractmitochondria energyproducing organelles neurons high energy consumption cells therefore mitochondrial dysfunction critical factor neurodegenerative processes mitochondrial division inhibitor1 mdivi1 small chemical inhibitor mitochondrial division dynamin plays multiple roles mitochondrial dynamics mitochondrial autophagy atp production immune response ca2+ homeostasis mdivi1 inhibition excessive mitochondrial fission exerted cytoprotective effects neurodegenerative diseases alzheimers disease ad parkinsons disease pd multiple sclerosis ms mdivi1 changed mrna expression electron transport chain etc reduced ca2+ overload neuronal injury elucidation molecular mechanism mdivi1 neurodegenerative diseases will help evaluate therapeutic potential promote application clinical studies present article focused multiple effects mdivi1 mitochondrial function potential therapeutic effects neurodegenerative diseasespmid35199329 doi1014670 hh18443,0.0
monitoring autoimmune diseases bioelectrochemical detection autoantibodies application determination antimyelin basic protein autoantibodies serum multiple sclerosis patients talanta 2022 feb 18 243123304 doi 101016 jtalanta2022123304 online ahead printabstractthis work reports amperometric bioplatform determination antimyelin basic protein autoantibodies antimbp relevant biomarker multiple sclerosis ms autoimmune disease developed configuration involves use carboxylated magnetic microparticles cmbs protein specific capture target autoantibodies covalently attached immobilized antimbp conjugated secondary antibody labelled horseradish peroxidase hrpantihigg amperometric transduction performed adding hydrogen peroxide using hydroquinone hq redox mediator cathodic current resulting reduction corresponding quinone directly proportional logarithmic concentration target autoantibodies analytical performance developed method determination antimbp competitive terms sensitivity range linearity claimed biosensor reported far literature well commercially available elisa kits showing remarkably shorter assay time bioplatform applied analysis serum samples healthy individuals patients diagnosed ms providing results agreement elisa methodologypmid35202838 doi101016 jtalanta2022123304,1.0
lung microbiome regulates brain autoimmunity nature 2022 feb 23 doi 101038 s41586022044274 online ahead printabstractlung infections smoking risk factors multiple sclerosis tcellmediated autoimmune disease central nervous system1 addition lung serves niche diseaseinducing t cells longterm survival maturation migrationcompetent effector t cells2 lung tissue particular important role autoimmune disease brain yet known detected tight interconnection lung microbiota immune reactivity brain dysregulation lung microbiome significantly influenced susceptibility rats developing autoimmune disease central nervous system shifting microbiota towards lipopolysaccharideenriched phyla local treatment neomycin induced typeiinterferonprimed state brainresident microglial cells responsiveness towards autoimmunedominated stimulation type ii interferons impaired led decreased proinflammatory response immune cell recruitment clinical signs suppressing lipopolysaccharideproducing lung phyla polymyxin b led disease aggravation whereas addition lipopolysaccharideenriched phyla lipopolysaccharide recapitulated neomycin effect data demonstrate existence lungbrain axis pulmonary microbiome regulates immune reactivity central nervous tissue thereby influences susceptibility autoimmune disease developmentpmid35197636 doi101038 s41586022044274,0.0
multiple sclerosis relapse following covid19 vaccination case report literature review cureus 2022 jan 18 14 1 e21374 doi 107759 cureus21374 ecollection 2022 janabstractmass vaccination coronavirus disease 19 covid19 effectively controlled pandemic remarkably effective safe reports adverse events reported postmarketing surveillance present rare case multiple sclerosis ms relapse female presented fatigue involuntary eye movements numbness autoimmunity following covid19 vaccine also described diagnosed ms six years back remission received covid19 vaccine 18 days ago clinical radiological features confirmed ms relapse serology covid19 immunoglobulin g igg igm positive managed intravenous methylprednisolone symptomatic management case provides possible association vaccineassociated ms relapse however evidence warranted future studiespmid35198286 pmcpmc8854205 doi107759 cureus21374,0.0
theoretical therapeutic implications spasticityplus syndrome model multiple sclerosis front neurol 2022 feb 7 12802918 doi 103389 fneur2021802918 ecollection 2021abstractin patients multiple sclerosis ms typical pattern muscle tone alteration known spasticity frequently observed combination signs symptoms spasms cramps pain bladder dysfunction sleep disturbances fatigue tremor recently concept spasticityplus syndrome sps proposed take account frequent coexistence complaints patients ms common pathophysiological basis putative new clinical entity proposed muscle tone sleep bladder function pain pathway controlled cannabinoid cb1 cb1r cb2 receptors cb2r particularly enriched brainstem axons smaller diameters particularly susceptible conduction block irritative ephaptic consequences demyelination involvement demyelination process caused ms brainstem might underlie various clinical manifestations sps adoption sps clinical practice useful improve symptomatic treatments significant proportion patients ms possibly limiting adverse events produced polypharmacotherapypmid35197915 pmcpmc8859110 doi103389 fneur2021802918,1.0
teriflunomide shifts astrocytic bioenergetic profile oxidative metabolism glycolysis attenuates tnfinduced inflammatory responses sci rep 2022 feb 23 12 1 3049 doi 101038 s41598022070247abstractastrocytes utilize glycolytic mitochondrial pathways power cellular processes vital maintaining normal cns functions cells also mount inflammatory acute phase reactive programs response diverse stimuli metabolic functions astrocytes homeostatic conditions wellstudied role cellular bioenergetics astrocyte reactivity poorly understood teriflunomide exerts immunomodulatory effects diseases multiple sclerosis metabolically reprogramming lymphocytes myeloid cells hypothesized teriflunomide constrain astrocytic inflammatory responses purified murine astrocytes grown serumfree conditions prevent acquisition spontaneous reactive state stimulation tnf activated nfb increased secretion lcn2 tnf stimulation increased basal respiration maximal respiration atp production astrocytes assessed oxygen consumption rate tnf also increased glycolytic reserve glycolytic capacity astrocytes change basal glycolytic rate assessed measuring extracellular acidification rate tnf specifically increased mitochondrial atp production secretion lcn2 required atp generated oxidative phosphorylation inhibition dihydroorotate dehydrogenase via teriflunomide transiently increased oxidative phosphorylation glycolysis quiescent astrocytes increased glycolytic atp production sustained time resulting bias away mitochondrial atp production even doses 1 m preconditioning teriflunomide prevented tnfinduced skew toward oxidative phosphorylation reduced mitochondrial atp production reduced astrocytic inflammatory responses suggesting drug may limit neuroinflammation acting metabolomodulatorpmid35197552 doi101038 s41598022070247,0.0
tissue damage detected quantitative gradient echo mri correlates clinical progression nonrelapsing progressive ms mult scler 2022 feb 2313524585211073761 doi 101177 13524585211073761 online ahead printabstractbackground imaging biomarkers progressive multiple sclerosis ms needed quantitative gradient recalled echo qgre magnetic resonance imaging mri evaluates microstructural tissue damage msobjective evaluate qgrederived r2t imaging biomarker ms progression compared atrophy lesion burdenmethods twentythree nonrelapsing progressive ms pms 22 relapsingremitting ms rrms 18 healthy control participants underwent standard ms physical cognitive neurological assessments imaging qgre flair mprage 3t pms subjects tested clinically imaged every 9 months 45 months imaging measures included lesion burden atrophy r2t cortical gray matter gm deep gm normalappearing white matter nawm longitudinal analysis clinical performance imaging biomarkers pms subjects conducted via linear models subject repeated withinsubject factor relationship imaging biomarkers clinical scores assessed spearman rank correlationresults r2t reductions correlated neurological impairment crosssectionally longitudinally pms patients clinically defined disease progression n 13 showed faster decrease r2t nawm deep gm compared clinically stable pms group n 10 importantly tissue damage measured r2t outperformed lesion burden atrophy biomarker progression study periodconclusion qgrederived r2t potential imaging biomarker ms progressionpmid35196933 doi101177 13524585211073761,0.0
selfreported safety bbibpcorv sinopharm covid19 vaccine among iranian people multiple sclerosis hum vaccin immunother 2022 feb 2416 doi 101080 2164551520222041945 online ahead printabstractto affirm shortterm safety bbibpcorv sinopharm covid19 vaccine among people multiple sclerosis pwms 517 vaccinated 174 unvaccinated pwms interviewed 162 vaccinated pwms reported least one neurological symptom respective vaccinerelated atrisk periods arp period first dose two weeks second dose vaccine multivariable logistic regression model presence comorbidities p 001 use natalizumab p 003 experiencing postvaccination myalgia p 001 predicted development postvaccination neurological symptoms one ms relapse one covid19 contraction one ulcerative colitis flare first dose four ms relapses second dose vaccine reported serious adverse events arps show vaccine provoked ms relapses compared relapse rate vaccinated pwms vaccinerelated arp annualized relapse rate unvaccinated pwms prior yeara measure baseline ms relapsing activity respective timeusing multivariable poisson regression model accounting possible confounders failed show statistically significant increase p 078 hence subject replicationas vaccinated unvaccinated pwms differed baseline characteristicsthe bbibpcorv vaccine seem affect shortterm ms activity furthermore 8333 unvaccinated pwms reported fear possible adverse events reason vaccination hesitancy provision evidencebased consultations pwms encouraged limitations study briefly included lack data selfcontrolled analysis relapse rates possible presence recall bias lack onsite validations regarding clinical outcomes due remote naturepmid35201963 doi101080 2164551520222041945,0.0
risk infections multiple sclerosis neuromyelitis optica spectrum disorder diseasemodifying treatments eighth european committee treatment research multiple sclerosis focused workshop review april 2021 mult scler 2022 feb 2313524585211069068 doi 101177 13524585211069068 online ahead printabstractover recent years treatment multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd evolved rapidly large number diseasemodifying treatments dmts now available however dmts associated adverse events frequent infections consideration dmtassociated risks facilitates development risk mitigation strategies international focused workshop expertled discussions sponsored european committee treatment research multiple sclerosis ectrims held april 2021 review current knowledge risk infections associated use dmts people ms nmosd corresponding risk mitigation strategies workshop addressed dmtassociated infections specific populations children pregnant women ms people ms comorbidities live regions exceptionally high infection burden finally reviewed topic dmtassociated infectious risks context current sarscov2 pandemic herein summarize available evidence identify gaps knowledge justify researchpmid35196927 doi101177 13524585211069068,0.0
cervical vestibular evoked myogenic potentials video head impulse test studies alternative methods detecting brainstem involvement multiple sclerosis acta otolaryngol 2022 feb 2417 doi 101080 0001648920222039759 online ahead printabstractbackground brainstem involvement bsi reported major predictive factor future disability multiple sclerosis ms aims objectives evaluate whether cervical vestibular evoked myogenic potentials cvemps video head impulse test vhit can used detect demyelinating lesions vestibular pathways msmaterial methods fifty three people ms 40 controls evaluated dizziness handicap inventory dhi vhit cvempresults median value dhi ms group significantly higher controls p001 according vhit results results horizontal canal vestibuloocular reflex gain group brain stem involvement gbsi + significantly different controls group without brain stem involvement gbsi p 036 024 respectively results gbsi similar controls p 858 cvemp results examined mean p1 wave latency gbsi + significantly longer controls p 002 difference gbsi controls gbsi + statistically significant p 104 279 respectively conclusions significance vhit cvemp can used diagnosis followup people ms without demyelinating brainstem lesions mripmid35200078 doi101080 0001648920222039759,1.0
curdlan microbial betaglucan contrasting effects autoimmune viral models multiple sclerosis front cell infect microbiol 2022 feb 7 12805302 doi 103389 fcimb2022805302 ecollection 2022abstractmultiple sclerosis ms immunemediated disease characterized inflammatory demyelination axonal degeneration central nervous system cns bacterial fungal infections associated development ms microbial components present several microbes contribute ms pathogenesis among components curdlan microbial 1 3glucan can stimulate dendritic cells enhances t helper th 17 responses determined whether curdlan administration affect two animal models ms autoimmune model experimental autoimmune encephalomyelitis eae viral model theilers murine encephalomyelitis virus tmev induced demyelinating disease tmevidd induced relapsingremitting eae sensitizing sjl j mice myelin proteolipid protein plp 139151 peptide found curdlan treatment prior plp sensitization converted clinical course eae hyperacute eae mice developed progressive motor paralysis died within 2 weeks curdlantreated eae mice massive infiltration t cells neutrophils cns higher levels th17 th1 responses compared control eae mice hand tmevidd found curdlan treatment reduced clinical scores axonal degeneration without changes inflammation viral persistence cns summary although curdlan administration exacerbated autoimmune ms model enhancing inflammatory demyelination suppressed viral ms model reduced axonal degeneration therefore microbial infections may play contrasting roles ms depending etiology autoimmunity versus viral infectionpmid35198458 pmcpmc8859099 doi103389 fcimb2022805302,1.0
common data elements facilitate sharing reuse participantlevel data assessment psychiatric comorbidity across brain disorders front psychiatry 2022 feb 7 13816465 doi 103389 fpsyt2022816465 ecollection 2022abstractthe ontario brain institutes braincode largescale informatics platform designed support collection storage integration diverse types data across several brain disorders means understand underlying causes brain dysfunction developing novel approaches treatment providing access aggregated datasets participants without different brain disorders braincode will facilitate analyses within across diseases cover multiple brain disorders wide array data including clinical neuroimaging molecular help achieve goals consensus methodology used identify set core demographic clinical variables routinely collected across participating programs establishment common data elements within braincode critical enable high degree consistency data collection across studies thus optimize ability investigators analyze pooled participantlevel data within across brain disorders results also presented using selected common data elements pooled across three studies better understand psychiatric comorbidity neurological disease alzheimers disease amnesic mild cognitive impairment amyotrophic lateral sclerosis cerebrovascular disease frontotemporal dementia parkinsons disease pmid35197877 pmcpmc8859302 doi103389 fpsyt2022816465,0.0
t1#x2f t2weighted ratio multiple sclerosis longitudinal study clinical associations neuroimage clin 2022 feb 16 34102967 doi 101016 jnicl2022102967 online ahead printabstractbackground t1w t2w ratio proposed clinically feasible mri biomarker assess tissue integrity multiple sclerosis however data available earliest stages disease longitudinal studies analysing clinical associations scarceobjective describe longitudinal changes t1w t2w patients clinically isolated syndrome cis multiple sclerosis investigate clinical associationsmethods t1w t2w images generated mean value obtained corresponding lesion normalappearing grey nagm white matter nawm masks coregistering baseline followup mri evolved lesions assessed placing mask new lesions baseline study prelesional tissue integrity measuredresults included 171 cis patients 22 established multiple sclerosis patients cis evolved lesions showed significant t1w t2w increases compared baseline +76 p 0001 t1w t2w values new lesions lower prelesional tissue 282 p 0001 prelesional tissue already lower baseline nawm 78 p 0001 cis baseline higher nagm t1w t2w associated multiple sclerosis diagnosis longitudinal decreases nagm nawm t1w t2w associated disease activity established multiple sclerosis t1w t2w inversely correlated clinical disability disease durationconclusion decrease t1w t2w ratio precedes lesion formation cis higher t1w t2w associated multiple sclerosis diagnosis established multiple sclerosis lower t1w t2w values associated clinical disability possible differential impact chronic inflammation iron deposition demyelination considered interpret findingspmid35202997 doi101016 jnicl2022102967,1.0
cytotoxic b cells relapsingremitting multiple sclerosis patients front immunol 2022 feb 7 13750660 doi 103389 fimmu2022750660 ecollection 2022abstractbackground emerging evidence antibodyindependent functions well clinical efficacy anticd20 depleting therapies helped reassess contribution b cells multiple sclerosis ms pathogenesisobjective investigate whether cd19+ b cells may share expression serineprotease granzymeb gzmb resembling classical cytotoxic cd8+ t lymphocytes peripheral blood relapsingremitting ms rrms patientsmethods study 104 rrms patients different treatments 58 healthy donors included cd8 cd19 runx3 gzmb expression assessed flow cytometry analysesresults rrms patients fingolimod fty natalizumab ntz treatment showed increased percentage circulating cd8+gzmb+ t lymphocytes compared healthy volunteers increase circulating cd19+gzmb+ b cells observed rrms patients fty ntz therapies compared glatiramer ga untreated rrms patients healthy donors compared interferon ifn moreover regarding runx3 transcriptional factor classically associated cytotoxicity cd8+ t lymphocytes expression gzmb significantly higher cd19+runx3+expressing b cells compared cd19+runx3 counterparts rrms patientsconclusions cd19+ b cells may exhibit cytotoxic behavior resembling cd8+ t lymphocytes ms patients different treatments future monitoring cytotoxic subsets might become accessible marker investigating ms pathophysiology even development new therapeutic interventionspmid35197967 pmcpmc8859463 doi103389 fimmu2022750660,0.0
neuroimmunology multiple sclerosis fictions facts front neurol 2022 feb 7 12796378 doi 103389 fneur2021796378 ecollection 2021abstractthere tremendous advances neuroimmunology multiple sclerosis past five decades led improved diagnosis therapy clinic however advances must take account understanding complex issues field particularly appreciation facts fiction surprisingly given incredible complexity nervous immune systems understanding basic biology disease incomplete lack understanding led many controversies field review identifies controversies facts fictions relation basic neuroimmunology disease cells molecules important clinical issues fortunately field healthy transition excessive reliance animal models broader understanding disease humans will likely lead many improved treatments especially neurodegeneration multiple sclerosis ms pmid35197914 pmcpmc8858985 doi103389 fneur2021796378,0.0
diverse injury responses human oligodendrocyte mediators implicated multiple sclerosis brain 2022 feb 24awac075 doi 101093 brain awac075 online ahead printabstractearly multiple sclerosis lesions feature relative preservation oligodendrocyte cell bodies dying back retraction myelinating processes cell loss occurs disease progression putative injury mediators include metabolic stress low glucose nutrient proinflammatory mediators interferon tumor necrosis factor excitotoxins glutamate objective compare impact disease relevant mediators injury responses human mature oligodendrocytes current study determined effects mediators process extension survival human brain derived mature oligodendrocytes vitro used bulk rna sequencing identify distinct effector mechanisms underlie responses mediators induced significant process retraction oligodendrocytes dissociated cell culture metabolic stress low glucose nutrient conditions resulted delayed 46 days nonapoptotic cell death metabolic effects associated induction integrated stress response can protective contribute cell injury dependent level duration activation addition sephin1 agonist integrated stress response induced process retraction control conditions enhanced retraction metabolic stress conditions antagonist isrib restored process outgrowth stress conditions added already stressed cells reduced delayed cell death prolonged period recovery occur inflammatory cytokine functional effects associated activation multiple signaling pathways including jak stat1 regulate process outgrowth without integrated stress response induction glutamate application produced limited transcriptional changes suggesting contribution effects directly cell processes comparative studies indicate need consider specific injury mediators distinct cellular mechanisms responses human oligodendrocytes identify effective neuroprotective therapies multiple sclerosispmid35202462 doi101093 brain awac075,1.0
excess use thyroid hormone treatment among patients fibromyalgia crosssectional study primary health care abstractobjectivefrom previous studies known association fibromyalgia thyroid autoimmunity diseases exists hand recently suggested many cases thyroid hormone treatment might unnecessary aim study explore thyroid hormone treatment among primary health care fibromyalgia patients study crosssectional based fibromyalgia study city nokia health center clinical examination performed participants patients filled five questionnaires information electronic patient records gathered addition parameters studied patients thyroid function levels beginning thyroid hormone treatmentresultsfrom patients participating study n 103 34 n 33 thyroid hormone treatment taking thyroid hormone treatment 48 n 16 information regarding initial tsh t4v levels beginning treatment 37 n 6 normal thyroid function small sample size data gathered single health center effects generalizability findings however suggest studies confirm potential association fibromyalgia inappropriate thyroid hormone treatment,0.0
possible roles sestrin2 multiple sclerosis relationships clinical outcomes abstract background characterized demyelination inflammation axonal damage multiple sclerosis ms one common disorders central nervous system led immune system urgent obvious need biomarkers diagnosis followup ms objective investigate serum levels sestrin2 sesn2 protein responds acute stress ms patients methods total 85 participants 40 patients diagnosed previously relapsingremitting ms 45 healthy controls included serum sesn2 parameters investigated blood samples drawn participant patient control groups results sesn2 levels significantly lower ms patients controls z 306 p0002 roc analysis sesn2 predictive level ms 236 ng ml sensitivity 7250 specificity 5556 p0002 area curve auc 0693 cutoff value groups sesn2 independent predictor ms exp b 3977 95 confidence interval 95ci 150710494 p0013 conclusions decreased expression sesn2 may play role ms pathogenesis sesn2 used biomarker ms immunotherapeutic agent treat ms,1.0
serum levels irisin nesfatin1 multiple sclerosis abstract background multiple sclerosis ms inflammatory neurodegenerative autoimmune chronic neurological disease currently effective serum biomarkers verify ms diagnosis assess disease prognosis evaluate response ms treatment objective present study preliminary assessment irisin nesfatin1 serum levels patients relapsing remitting ms rrms methods total 86 participants 42 patients rrms diagnosis 44 healthy controls included study serum irisin nesfatin1 parameters patients control group members analyzed results irisin nesfatin1 levels rrms patients significantly lower controls z 382 p0001 z 479 p0001 respectively cutoff level irisin 10390 ng ml sensitivity 841 specificity 714 auc 0800 cutoff level nestatin1 7155 ng ml sensitivity 682 specificity 643 auc 0739 roc analysis cutoff levels casecontrol groups lower irisin nesfatin1 levels independent variables ms patients 9723 95ci 288432785 p0001 3992 95ci 133611928 p0001 respectively conclusion present study revealed lower irisin nesfatin1 levels patients rrms findings suggest decreased levels irisin nesfatin1 peptides may contribute ms pathogenesis inflammation oxidative stress apoptosis ms leading demyelination axonal damage neuronal loss gliosis,1.0
stable vs silent progressive multiple sclerosis realworld retrospective clinical imaging brazilian study abstract background clinical imaging required characterize activity progression ms parameters activity well defined progression ideal aim longterm treatment neither clinical imaging signs disease present also brain atrophy objectives conduct comparative clinicalimaging study focusing mri brain volumetry methods 174 consecutive relapsingremitting ms patients mcdonald 2001 studied focusing activity progression annual clinical evaluations relapse rate edss mri data along annualized evolution corpus callosum index cci compared results 174 patients 148 considered clinically stable based edss however 33 222 group showed annualized reductions cci 05 cutoff defining significant brain atrophy conclusions among apparently stable relapsingremitting ms patients 1 5 showed significant brain atrophy followup period least 7 years consider reasonable suggest mri volume sequences included followup protocols provide information real treatment response status,0.0
effect 12 weeks aquatic strength training individuals multiple sclerosis resumo antecedentes programas de exerccios fsicos recomendados para pacientes com esclerose mltipla entanto limitados os estudos que envolvem o treinamento aqutico de fora para melhoria das capacidades funcionais objetivo investigar o efeito de um programa de treinamento aqutico de fora nas capacidades funcionais e nos nveis de fora e fadiga de pessoas diagnosticadas com esclerose mltipla mtodos foram selecionados 29 voluntrios com esclerose mltipla todos os participantes realizaram uma bateria de testes incluindo os de capacidades funcionais nvel de fora e nveis de fadiga em dois momentos distintos printerveno e psinterveno o programa de treinamento de fora foi realizado durante 12 semanas foram utilizados exerccios de fora localizados com controle especfico de carga de trabalho que variou entre 50 e 90 mximo de acordo com semana de treinamento para anlise estatstica optouse por utilizar o teste t de student na comparao ente os momentos pr e psinterveno resultados os resultados demonstraram melhora significativa em todas variveis investigadas teste de 6 min de caminhada p0 00 fora mo dominante p0 02 fora mo dominante p0 00 levantar p0 00 sentar e levantarse p0 00 subir 15 degraus p0 00 descer 15 degraus p0 00 calar meias p0 00 gravidade da fadiga p0 01 impacto da fadiga p0 01 concluso o treinamento aqutico de fora foi eficiente para melhorar capacidades funcionais relacionadas qualidade de vida de pacientes com esclerose mltipla,0.0
coexistence restless legs syndrome multiple sclerosis aggravates anxiety depression abstract background among comorbidities accompany multiple sclerosis ms restless legs syndrome rls one common anxiety depression common psychological comorbidities impact quality life patients ms pwms well patients rls objective investigate psychiatric burden ms rls coexistence conducted nationwide multicenter crosssectional survey methods participants assessed using demographic clinical parameters along hamilton anxiety hamilton depression scales hama hamd results 1 068 participants 173 162 found rls rls + 895 838 rls mean scores hama hamd significantly higher among rls + subjects among rls subjects p0001 variables conclusions according data presence rls pwms may increase occurrence anxiety depression symptoms awareness treatment rls pwms possibly reduce symptoms psychiatric comorbidities originating rls,0.0
autoimmune disease interconnections vitamin d endocr connect 2022 feb 1ec210554 doi 101530 ec210554 online ahead printabstractvitamin d well documented effects calcium homeostasis bone metabolism recent studies suggest much broader role secosteroid human health key components vitamin d system notably vitamin d receptor vdr vitamin d activating enzyme 1hydroxylase present wide array tissues notably macrophages dendritic cells t lymphocytes t cells immune system thus serum 25hydroxyvitamin d 25d can converted hormonal 1 25dihydroxyvitamin d 1 25d within immune cells interact vdr promote transcriptional epigenomic responses neighbouring cells intracrine paracrine effects 1 25d shown drive antibacterial antiviral innate responses well attenuating inflammatory t cell adaptive immunity beyond mechanistic observations association studies reported correlation low serum 25d levels risk severity human immune disorders including autoimmune diseases inflammatory bowel disease multiple sclerosis type 1 diabetes rheumatoid arthritis proposed explanation decreased availability 25d compromises immune cell synthesis 1 25d leading impaired innate immunity overexuberant inflammatory adaptive immunity aim current review explore mechanistic basis immunomodulatory effects 25d 1 25d greater detail specific emphasis vitamin ddeficiency low serum levels 25d may lead dysregulation macrophage dendritic cell t cell function increase risk inflammatory autoimmune diseasepmid35196255 doi101530 ec210554,0.0
disease course chronic relapsing inflammatory optic neuropathy crion single care center arq neuropsiquiatr 2022 feb 21s0004282x2022005003211 doi 101590 0004282xanp20210157 online ahead printabstractbackground chronic relapsing inflammatory optic neuropathy crion recurrent idiopathic optic neuritis considered rare diseaseobjective describe clinical course longterm followup patients diagnosis crionmethods cohort 1 735 patients demyelinating disorders selected patients aged 16 years crion according current criteria demographic clinical data including initial presentation symptoms number relapses time delay diagnosis diagnostic methods treatment obtained clinical files infections autoimmune diseases multiple sclerosis among conditions ruled patientsresults analyzed 30 patients crion 24 women six men mean age 428102 years median disease course 79 years 529131 median number attacks 2 iqr 24 initial manifestation ocular pain 97 bilateral sequential affection 87 visual acuity recovered 50 improve 33 recovered incompletely 17 antibodies aquaporin4 aqp4abs negative 733 magnetic resonance imaging brain normal 767 none patients evolved another demyelinating disease time initial treatment methylprednisolone 100 plasmapheresis 20 currently patients maintenance treatment mycophenolate mofetil rituximab decrease relapsing rateconclusions diagnosis crion challenging kept mind prompt diagnosis adequate treatment close followup essential prevent disabling sequelae patientspmid35195230 doi101590 0004282xanp20210157,1.0
immune response sarscov2 vaccination relation peripheral immune cell profiles among patients multiple sclerosis receiving ocrelizumab j neurol neurosurg psychiatry 2022 feb 22jnnp2021328197 doi 101136 jnnp2021328197 online ahead printabstractbackground vaccination proven effective preventing sarscov2 transmission severe disease courses however immunocompromised patients included clinical trials realworld clinical data point attenuated immune response sarscov2 vaccines among patients multiple sclerosis ms receiving immunomodulatory therapiesmethods performed retrospective study including 59 ocrelizumab ocr treated patients ms received sarscov2 vaccination antisarscov2antibody titres routine blood parameters peripheral immune cell profiles measured prior first baseline median 4 weeks second vaccine dose followup moreover sarscov2specific t cell response peripheral b cell subsets analysed followup finally vaccinationrelated adverse events assessedresults vaccination found antisarscov2 s antibodies 271 sarscov2specific t cell response 927 ms cases t cellmediated interferon ifn release pronounced patients without antisarscov2 s antibodies antibody titres positively correlated peripheral b cell counts time since last infusion total igm levels negatively correlated number previous infusion cycles peripheral plasma cells increased antibodypositive patients positive correlation t cell response peripheral lymphocyte counts observed moreover ifn release negatively correlated time since last infusionconclusion ocrtreated patients ms humoral immune response sarscov2 vaccination attenuated t cell response preserved however still unclear whether t b cellmediated immunity required effective clinical protection nonetheless given longlasting clinical effects ocr monitoring peripheral b cell counts facilitate individualised treatment regimens might used identify optimal time vaccinatepmid35193952 doi101136 jnnp2021328197,0.0
hormone therapy disease activity danish women multiple sclerosis populationbased cohort study eur j neurol 2022 feb 23 doi 101111 ene15299 online ahead printabstractbackground sex differences multiple sclerosis ms prevalence disease course thought driven hormones exogenous exposure estrogens may affect ms disease course thus aim investigate association hormone therapy ht disease activity disability accrual among women msmethods registerbased cohort study prospectively enrolled cases danish ms registry information hormone exposure retrieved national prescription registry outcomes relapse rate relapse rate ratio recurrent relapses 6month confirmed sustained expanded disability status scale edss milestone 4 6 recurrent edss worseningresults 3 325 women eligible analyses 333 10 ever ht sometime followup found association ht disability accrual although trend increasing risk increasing length use seen risk reaching 6month confirmed sustained edss 4 among users 06 95 ci 0312 less one year use 14 95 ci 0922 five years ht compared never use risk recurrent relapse increased 20 95 ci 1014 among current users ht compared nonusers however risk recurrent relapses driven first calendar period 19962005 introduction high efficacy dmtsconclusions findings nationwide ms population suggest ht affect disability accrual women ms especially used less five yearspmid35196406 doi101111 ene15299,0.0
curing inflammatory diseases using phosphorous dendrimers wiley interdiscip rev nanomed nanobiotechnol 2022 feb 22e1783 doi 101002 wnan1783 online ahead printabstractdifferent types watersoluble phosphorous dendrimers synthesized display many different biological properties shown particular phosphorous dendrimers first generation functionalized azabisphosphonate terminal functions able stimulate human immune system ex vivo dendrimers internalized monocytes within seconds induce antiinflammatory activation presence dendrimers induces also inhibition differentiation monocytes osteoclasts maturation dendritic cells inhibits proliferation proinflammatory cd4+ t lymphocytes finally 23 weeks culture peripheral blood mononuclear cells amplifications several tens natural killer cells observed view properties influence azabisphosphonatedendrimers tested vivo several animal models different chronic acute inflammatory diseases multiple sclerosis rheumatoid arthritis uveitis psoriasis also myeloid leukemia hematological cancer hematological safety demonstrated mice platelet aggregation hemolysis disturbance hematological formula safety azabisphosphonatedendrimer assessed also nonhuman primates cynomolgus monkeys received repeated injections derisking preclinical test biochemical hematological immunological parameters peripheral blood remained within normal physiological range throughout study survived well phosphorous dendrimers also display antiinflammatory properties vivo particular dendrimers functionalized mannose derivatives prevent acute lung diseases given orally per os mice article categorized nanotechnology approaches biology nanoscale systems biology therapeutic approaches drug discovery emerging technologies therapeutic approaches drug discovery nanomedicine neurological diseasepmid35194953 doi101002 wnan1783,0.0
postcorona fatigueafamiliar picture anew guise onkologe berl 2022 feb 1716 doi 101007 s00761022011021 online ahead printabstractbackground myalgic encephalitis chronic fatigue syndrome cfs come focus result coronavirus disease 2019 covid19 fundamentally problematic fact cfs considered separate entity however extreme fatigue also common symptom underlying disease article aims increase acceptance cfs extreme fatigue facing symptomatology fully understood highlight need research orientation physicians counselling services patientsmaterials methods orientative research focused information gatheringresults various research projects hypothesis postinfectious cfs autoimmune disease confirmed general heterogeneity diagnostic criteria well variety formulations describe symptomatology different coding options make difficult clearly assign symptoms clinical picture exertion intolerance identified severe symptom postcovid19 disorder reason recommendations international guidelines currently revised especially regard pacing implications recommendations tumorrelated fatigue due multiple sclerosis unclearconclusion background decreasing burden disease due increasing vaccination rates research fatigue include viral diseasespmid35194336 pmcpmc8853121 doi101007 s00761022011021,0.0
jak1 signaling dendritic cells promotes peripheral tolerance autoimmunity pdl1mediated regulatory tcell induction cell rep 2022 feb 22 38 8 110420 doi 101016 jcelrep2022110420abstractdendritic cells dcs induce peripheral t cell tolerance cellintrinsic signaling cascades governing stable tolerogenesis remain poorly defined janus kinase 1 jak1 transduces cytokinereceptor signaling jak inhibitors jakinibs including jak1specific filgotinib break inflammatory cycles autoimmunity report heterogeneous dc populations multiple secondary lymphoid organs jak1 promotes peripheral t cell tolerance experimental autoimmune encephalomyelitis eae mice harboring dcspecific jak1 deletion exhibit elevated peripheral cd4+ t cell expansion less regulatory t cells tregs worse eae outcomes whereas adoptive dc transfer ameliorates eae pathogenesis inducing peripheral tregs programmed cell death ligand 1 pdl1 dependently tolerogenic program substantially reduced upon transfer jak1deficient dcs dcintrinsic ifnjak1stat1 signaling induces pdl1 required dcs convert cd4+ t cells tregs vitro attenuated upon jak1 deficiency filgotinib treatment thus dcintrinsic jak1 promotes peripheral tolerance suggesting potential unwarranted dcmediated effects jakinibs autoimmune diseasespmid35196494 doi101016 jcelrep2022110420,0.0
melanocortin 1 receptor activation protects alphasynuclein pathologies models parkinsons disease background epidemiological studies suggest link melanomarelated pigmentation gene melanocortin 1 receptor mc1r risk parkinsons disease pd previously showed mc1r signaling can facilitate nigrostriatal dopaminergic neuron survival present study investigates neuroprotective potential mc1r neurotoxicity induced alphasynuclein syn key player pd genetics pathogenesismethodsnigral dopaminergic neuron toxicity induced local overexpression asyn assessed mice inactivating mutation mc1r overexpress wildtype transgene treated mc1r agonists role nuclear factor erythroid 2related factor 2 nrf2 mc1rmediated protection syn characterized vitro furthermore mc1r expression determined human postmortem midbrain patients pd unaffected subjectsresultstargeted expression syn nigrostriatal pathway induced exacerbated synuclein pathologies mc1r mutant mice accompanied neuroinflammation altered nrf2 responses reversed human mc1r transgene two mc1r agonists neuroprotective syninduced dopaminergic neurotoxicity vitro experiments showed nrf2 necessary mediator mc1r effects lastly mc1r present dopaminergic neurons human substantia nigra appeared reduced tissue level pd patientsconclusionour study supports interaction mc1r syn can mediated neuronal mc1r possibly nrf2 provides evidence mc1r therapeutic target rationale development mc1ractivating strategies pd,1.0
b celldependent eae induces visual deficits mouse similarities human autoimmune demyelinating diseases background field autoimmune demyelinating diseases visual impairments extensively studied using experimental autoimmune encephalomyelitis eae mouse model classically induced immunization myelin oligodendrocyte glycoprotein peptide mog3555 however model involve b cells like human analogs new antigens thus developed induce b celldependent form eae better mimics human diseasesmethodsthe present study aimed characterize visual symptoms eae induced antigen called bmog induction eae bmog c57bl 6j mice visual function changes studied electroretinography optomotor acuity tests motor deficits assessed parallel standard clinical scoring method histological examinations western blot analyses allowed follow retinal neuron survival gliosis microglia activation opsin photopigment expression photoreceptors optic nerve demyelination disease effects retinal gene expression established rna sequencingresultswe observed bmog eae mice exhibited persistent loss visual acuity despite partial recovery electroretinogram motor functions loss likely due retinal inflammation gliosis synaptic impairments evidenced histological transcriptomic data analysis suggests mcone photoreceptor pathway also affectedconclusiontherefore documenting visual changes induced bmog showing similarities seen diseases multiple sclerosis neuromyelitis optica study offers new approach test protective restorative ophthalmic treatments,1.0
burden multiple sclerosis among postpartum women self management#39 s challenges pilot study supportive program egypt abstractbackgroundthis study aims determine effect multiple sclerosis supportive programs mothersnull selfmanagement postpartumstudy designa quasiexperimental nonequivalent group design utilized primigravida pregnant women 3537 weeks gestation recently diagnosed multiple sclerosis participated two preparation sessions first session pregnancy open conversation delivery key topics second session nature postpartum cycle expected relapsesresultsseventy pregnant women multiple sclerosis participated research results denoted statistical difference groups regarding selfmanagement 6th 12th weeks postpartum improvements related mothersnull relationships health care providers knowledge information multiple sclerosis transitional phase hand differences among groups related levels functional activities 6th 12th weeks postpartum although slight deterioration motor ability score among groups 12th weeknulls postpartum 543 intervention group vs 49 nonintervention group reported 100 absolute independence moreover total relapses threemonth postpartum ranged 16 increasing frequency relapses threemonth postpartum statistically significant differences groupsconclusionconducting multidisciplinary program follow counsel mothers ms helps enhance selfmanagement throughout threemonth postpartum period,0.0
pediatric antiphospholipid syndrome clinical features therapeutic interventions single center retrospective case series background purposepediatric antiphospholipid syndrome aps thromboinflammatory disease characterized presence circulating antiphospholipid antibodies either thrombotic events pregnancy morbidity objective study review large institutions experience better understand characteristics children apsmethodswe conducted retrospective review pediatric aps tertiary referral center electronic medical record system queried 2000 2019 21 cases included based meeting revised sapporo classification criteria age 18 younger comparisons primary secondary aps patients made twotailed ttestsresultstwentyone patients included median age diagnosis 16 years median followup 58 years secondary aps slightly common primary aps 11 vs 10 cases primarily diagnosed context systemic lupus erythematosus two thirds patients 67 also noncriteria manifestations aps including thrombocytopenia autoimmune hemolytic anemia livedo reticularis racemosa almost half patients 43 recurrent thrombosis typically patients subtherapeutic nonadherent anticoagulation damage index patients thrombotic aps diaps scores indicated chronic burden disease primary secondary aps patientsconclusionthis case series pediatric aps provides important context regarding disease phenotypes displayed children aps high prevalence noncriteria clinical manifestations highlights need consider characteristics developing pediatricspecific classification criteria considering relatively rare diagnosis pediatric practice,0.0
progressive buildup perineuronal nets somatosensory cortex associated development chronic pain mice chronic pain sustained maladaptive form neuronal plasticity occurring stations pain neuraxis including cortical regions pain matrix report chronic inflammatory pain induced unilateral injection complete freunds adjuvant cfa hindpaw male mice associated progressive buildup perineuronal nets pnns contralateral somatosensory cortex ssctx medial prefrontal cortex mpfctx reticular thalamic nucleus ssctx density pnns labeled wisteria fluribunda agglutinin wfa increased 3 7 days following cfa injection 7 days mpfctx number parvalbumin pv positive interneurons enwrapped wfa+ pnns also increased three brain regions mice injected cfa remarkably pnn degradation induced intracortical infusion chondroitinaseabc significantly reduced mechanical thermal pain also reversed increased frequency inhibitory postsynaptic currents ipscs recorded layer 5 pyramidal neurons contralateral ssctx cfainjected mice findings suggest possible relationship cortical pnns nociceptive sensitization support hypothesis pnns maintain plasticity adult life regulate cortical responses sensory inputssignificance statementthe brain extracellular matrix provides structural support also regulates synapse formation function modulates neuronal excitability found chronic inflammatory pain mice enhances density perineuronal nets pnns somatosensory cortex medial prefrontal cortex remarkably enzymatic degradation pnns somatosensory cortex caused analgesia reversed alterations inhibitory synaptic transmission associated chronic pain findings disclose novel mechanism nociceptive sensitization support role pnns mechanisms neuronal plasticity adult brain,0.0
correction impact covid19 pandemic frequency clinical visits performance mri studies therapeutic choices multiple sclerosis referral centre j neurol 2022 feb 22 doi 101007 s00415022110199 online ahead printno abstractpmid35192034 doi101007 s00415022110199,0.0
application extracellular vesicles derived mesenchymal stem cells potential therapeutic tools autoimmune rheumatic diseases int immunopharmacol 2022 feb 19 106108634 doi 101016 jintimp2022108634 online ahead printabstractmesenchymal stem cells mscs proven superior potential used astherapeutic candidates various disorders nevertheless clinical application cells restricted tumorigenic properties increasing evidence established valuable impacts mscs mainly attributable paracrine factors including extracellular vesicles evs evs nanosized doublelayer phospholipid membrane vesicles contain various proteins lipids mirnas mediate celltocell communications due inferior immunogenicity tumorigenicity well easier management evs drawn attention potential cellfree replacement therapy mscs reason herein reviewed recent findings researches different mscevs effectiveness treatment several autoimmune rheumatic diseases including multiple sclerosis inflammatory bowel disease rheumatoid arthritis osteoarthritis osteoporosis systemic lupus erythematosus well sjogrens syndrome systemic sclerosis autoimmune diseasespmid35193053 doi101016 jintimp2022108634,0.0
flu vaccination multiple sclerosis patients monocentric prospective vaccinevigilance study expert opin drug saf 2022 feb 22 doi 101080 1474033820222044787 online ahead printabstractbackground 2020 italian medicines agency recommended bring forward flu vaccination campaign whose importance also emphasized patients multiple sclerosis ms aimed assess safety profile flu vaccines terms occurrence shortterm longterm adverse events following immunization aefis methods observational study enrolled ms patients eligible flu vaccines recommended italian medicines agencyresults 194 patients enrolled 133 patients accepted vaccinated 45 experienced serious shortterm aefis pain injection site headache flulike symptoms fatigue longterm aes detected 12 vaccinated patients flulike symptoms covid19 ms relapse statistically significant differences terms infections ms relapse found vaccinated unvaccinated groups using kaplanmeier analysis observed differences cumulative survival rate groupsconclusion flu vaccines well tolerated ms patients mainly experienced serious short term aefis considering covid19 vaccines campaign still ongoing among ms patients results might bring new knowledge concerning safety profile vaccines frail populationpmid35189777 doi101080 1474033820222044787,0.0
ocrelizumab review multiple sclerosis drugs 2022 feb 22 doi 101007 s40265022016729 online ahead printabstractocrelizumab ocrevus intravenously administered humanized anticd20 monoclonal antibody approved treatment adults relapsing forms multiple sclerosis rms primary progressive multiple sclerosis ppms efficacy ocrelizumab reducing relapse rates disease activity patients rms demonstrated pivotal trials versus interferon 1a supporting singlearm studies specific subpopulations patients ppms ocrelizumab reduced measures clinical mri progression relative placebo clinical benefits maintained 75 study years treatment ocrelizumab generally well tolerated new safety signals emerged longterm use extensive albeit shortterm realworld data pertaining ocrelizumab consistent clinical trials ocrelizumab provides convenience short halfyearly infusions ocrelizumab continues represent generally welltolerated highefficacy diseasemodifying therapy dmt rms valuable treatment delaying disease progression patients ppms currently approved dmts pmid35192158 doi101007 s40265022016729,0.0
role glial cells multiple sclerosis disease progression nat rev neurol 2022 feb 21 doi 101038 s4158202200624x online ahead printabstractdespite development highly effective treatments relapsingremitting multiple sclerosis ms limited progress made addressing primary progressive secondary progressive ms lead loss oligodendrocytes neurons axons irreversible accumulation disability neuroinflammation central forms ms current effective therapies relapsingremitting ms target peripheral immune system treatments however repeatedly failed progressive ms greater understanding inflammation driven cnsresident cells including astrocytes microglia therefore required identify novel potential therapeutic opportunities advances imaging biomarker analysis genomics suggest microglia astrocytes central roles progressive disease process review provide overview involvement astrocytes microglia major sites pathology progressive ms discuss current future therapeutic approaches directly target glial cells either inhibit pathogenic functions restore homeostatic functions lost course disease also discuss bidirectional communication astrocytes microglia needs considered therapeutic targeting one likely alter functions otherpmid35190704 doi101038 s4158202200624x,0.0
correction bloodbrain barrier breakdown nonenhancing multiple sclerosis lesions detected 7tesla mp2rage deltat1 mapping plos one 2022 feb 22 17 2 e0264452 doi 101371 journalpone0264452 ecollection 2022abstract corrects article doi 101371 journalpone0249973 pmid35192677 doi101371 journalpone0264452,0.0
efficacy safety masitinib progressive forms multiple sclerosis randomized phase 3 clinical trial neurol neuroimmunol neuroinflamm 2022 feb 21 9 3 e1148 doi 101212 nxi0000000000001148 print 2022 mayabstractbackground objectives masitinib selective tyrosine kinase inhibitor targeting innate immune cells mast cells microglia involved pathophysiology progressive multiple sclerosis ms study ab07002 assessed oral masitinib patients progressive ms progressing clinically activemethods randomized doubleblind 2 parallelgroup placebocontrolled trial assessing 2 dose levels masitinib vs equivalent placebo conducted 116 hospital clinics specialized ms centers 20 countries randomization 21 minimization performed centrally using automated system patients physicians outcome assessors remained masked treatment group allocation patients primary progressive ms ppms nonactive secondary progressive ms nspms without relapse 2 years aged 1875 years baseline expanded disability status scale edss 2060 regardless time onset treated 96 weeks primary end point overall edss change baseline using repeated measures generalized estimating equation timeframe w12w96 measured every 12 weeks positive values indicating increased clinical deterioration efficacy safety assessed randomly assigned treated patientsresults total 611 patients randomized 301 masitinib 45 mg kg d parallel group 310 uptitrated masitinib 60 mg kg d parallel group masitinib 45 mg kg d n 199 showed significant benefit placebo n 101 according primary end point 0001 vs 0098 respectively betweengroup difference 0097 97 ci 0192 0002 p 00256 safety consistent masitinibs known profile diarrhea nausea rash hematologic events elevated risk infection efficacy results independent uptitrated masitinib 60 mg kg d parallel group inconclusive new safety signal observeddiscussion masitinib 45 mg kg d can benefit people ppms nspms confirmatory phase 3 study will initiated substantiate datatrial registration information first participant randomized study ab07002 august 25 2011 trial registered european clinical trials database #eudract 201002121917 july 1 2011 clinicaltrialsregistereu ctrsearch trial 201002121917 es clinicaltrialsgov #nct01433497 september 14 2011 clinicaltrialsgov ct2 show nct01433497 classification evidence study provides class ii evidence masitinib 45 mg kg d decreased progression disability measured edss adults ppms patients nspms exacerbations last 2 years pmid35190477 doi101212 nxi0000000000001148,0.0
multiple sclerosis patientoriented multiomics analysis tells us go next commentary alterations hostgut microbiome interactions multiple sclerosis gut microbiota profound influences human health close interactions host emergence nextgeneration sequencing gnotobiotic technologies allowed us understand overall picture gut microbiota explore functional significance alterations gut studies identified specific microbial taxa associated various human diseases research focusing central nervous system cns diseases growing interest socalled gutbrain axis assumes impact intestinal environment brain health cns disordersmultiple sclerosis ms autoimmune demyelinating disease cns onset young adulthood studies indicate number patients ms now estimated 28 million increasing decades world pooled incidence rate since 2013 across 75 reporting countries 21 per 10 000 persons year1 genetic risk factors ms considered unchanged period time nongenetic risk factors account increase ms among various risk factors ms importance gut microbiota highlighted recent studies2 3 4 5 6 following discovery dysbiosis increased decreased taxa associated ms including reduction butyrateproducing bacteria 1 2 functional significance altered microbiome investigated study fecal microbiota ms patients healthy subjects transferred germfree mice recipient mice immunized myelin antigen inducing conventional mouse model ms experimental autoimmune encephalomyelitis eae 4 clinical signs eae reflecting cns inflammation induced th17 cells serious mice transferred ms patientderived fecal samples compared transferred fecal samples healthy subjects another study fecal microbiota samples transferred tcr transgenic mice spontaneously develop signs ms5 results study essentially similar 4 indicating microbiota ms patients diseaseenhancing effects compared healthy subjectsdietary contents changed dramatically last decades change characterized reduction dietary fiber increase highfat consumption published data healthy subjects gnotobiotic mice revealed dietary changes may strongly affect structure gut microbiota accordingly can argued reduction scfa production gut patients japanese patients ms may result westernization lifestyle7 previous epidemiological studies regarding diet ms patients also supports hypothesiswhile comprehensive microbiome data gradually accumulating last five years limited number studies evaluated interactions microbial components various sources clinical laboratory data based multilayered analysis issue ebiomedicine cantoni et al performed elegant series multiomics analysis based data gut microbiome peripheral immune cells serum metabolites dietary contents obtained 24 ms patients 25 healthy subjects8 revealed significant correlation increase total intake meat increased abundance peripheral t helper 17 th17 cells corresponding gut microbial components serum metabolites patients ms obtained results support previously proposed axis 7 starting reduced intake dietary fiber reduction scfa production gut causes reduced frequency peripheral regulatory t cells enhancement cns inflammation6 9 study conclusively showed close interactions commensal microorganisms ms concert previous recent studies demonstrating significant role diet ms9while oral intake longchain fatty acids lcfa leads induction th17 cells worsening eae 8 shortchain fatty acids butyrate proprionate seems preventive development eae9 consistently recent clinical study revealed oral proprionic acid treatment ms induces regulatory t cells stabilize clinical course ms10 given diet dietary components play role immune system increased efforts directed towards exploring similarity gut microbiome among family members sharing diet8although results persuasive due power advanced multiomics analysis study8 several limitations patient cohort relatively small touch differences disease subtypes ms relapsing remittingms progressive ms additional information regarding disease activity clinical severity ms patients help obtain deeper insights pathogenesis another limitation study whether result cause consequence ms verification experiments using rodent model will enhance scientific significance studyeven little scientific evidence information management ms like desirable diet ms attract attention patients often rejected scorned new findings paper8 clearly support role diet pathogenesis ms strong impact biological research clinical practice daily life although results past 16s rrna analysis problems reproducibility across countries laboratories multiomics data8 provided affirmation dysbiosis altered gut microbiome ms real phenomenon summary work opens way diet microbiome dataassisted management ms useful prevention disease progression,1.0
changes intraocular pressure ocular pulse amplitude rhesus macaques blue light scleral crosslinking background scleral crosslinking can enhance biomechanical strength sclera expected new operative method prevention myopia however studies investigating changes intraocular pressure iop ocular pulse amplitude opa blue lightriboflavin induced scleral collagen crosslinking sxl rhesus monkeys limited study aimed investigate changes iop opa threeyearold rhesus macaques 1 week 1 month 3 months blue lightriboflavin sxlmethodsseven threeyearold rhesus macaques 14 eyes randomly divided two groups 4 monkeys group 8 eyes 3 monkeys group b 6 eyes right eye rhesus macaque used experimental eye whereas left eye used control group one quadrant right eye irradiated group b two quadrants right eye one quadrant left eye irradiated iop opa eyes measured seven rhesus macaques sxl 1 week 1 month 3 months postoperatively differences iop opa experimental control eyes evaluated via paired t testresultsin groups b significant differences experimental control eyes iop opa sxl 1 week 1 month 3 months postoperatively p 005 conclusionsthe iop opa significantly affected 1 vs 0 1 vs 2 quadrants blue light sxl,0.0
endocannabinoid system zebrafish potential study effects cannabis humans abstractzebrafish considered unprecedented animal model drug discovery review literature presents highlights elucidates biological effects chemical components found cannabis sativa particular attention paid endocannabinoid system ecb main receptors cb1 cb2 zebrafish model promising one study cannabinoids many similarities human system despite recent advances ecb system still need elucidate interactions thus zebrafish model can used purpose respects 3rs concept reduced time costs view relevance cannabinoids treatment prevention diseases well importance zebrafish animal model elucidating biological effects new drugs aim study bring light information use zebrafish animal model testing c sativabased medicines,0.0
determinants prevaccination antibody responses sarscov2 populationbased longitudinal study covidence uk background prospective populationbased studies investigating multiple determinants prevaccination antibody responses sarscov2 lackingmethodswe prospective populationbased study sarscov2 vaccinenaive uk adults recruited may 1 november 2 2020 without positive swab test result sarscov2 prior enrolment information 88 potential sociodemographic behavioural nutritional clinical pharmacological risk factors obtained online questionnaires combined igg iga igm responses sarscov2 spike glycoprotein determined dried blood spots obtained november 6 2020 april 18 2021 used logistic linear regression estimate adjusted odds ratios aors adjusted geometric mean ratios agmrs potential determinants sarscov2 seropositivity participants antibody titres seropositive participants respectivelyresultsof 11 130 participants 1696 152 seropositive factors independently associated higher risk sarscov2 seropositivity included frontline health care occupation aor 186 95 ci 148233 international travel 120 107135 number visits shops indoor public places 5 vs 0 week 129 106157 ptrend 001 body mass index bmi 25 vs 25 kg m2 124 111139 south asian vs white ethnicity 165 110249 alcohol consumption 15 vs 0 units week 123 104146 light physical exercise associated lower risk 080 070093 10 vs 04 h week among seropositive participants higher titres antispike antibodies associated factors including bmi 30 vs 25 kg m2 agmr 110 102119 south asian vs white ethnicity 122 104144 frontline health care occupation 124 95 ci 111139 international travel 111 105116 number visits shops indoor public places 5 vs 0 week 112 102123 ptrend 001 associations substantially attenuated adjustment covid19 disease severityconclusionshigher alcohol consumption lower light physical exercise represent new modifiable risk factors sarscov2 infection recognised associations south asian ethnic origin obesity higher risk sarscov2 seropositivity independent sociodemographic behavioural nutritional clinical pharmacological factors investigated among seropositive participants higher titres antispike antibodies people south asian ancestry obese people explained greater covid19 disease severity groups,0.0
identifying unanswered questions setting agenda future systematic research multiple sclerosis worldwide multistakeholder priority setting project abstractbackgroundeliciting research priorities people affected condition carers health care professionals can increase research value reduce research waste cochrane multiple sclerosis rare disease cns group collaboration cochrane neurological sciences field launched priority setting exercise aim prioritizing pressing questions ensure future systematic reviews useful possible people need countries regardless economic statusmethodsixteen high priority questions different aspects ms developed members multistakeholder priority setting steering group sg anonymous online survey translated 12 languages researchers clinicians people ms pwms carers asked identify rank 5 16 questions high priority provide explanation choice additional freetext priority research topic suggestion allowedresultsthe survey accessible ms advocacy associations social media cochrane web pages october 20 2020 february 6 2021 1190 responses 8673 web contacts evaluable included analysis responses came 55 countries worldwide 7 provided 75 respondents 95 high uppermiddle income countries 588 respondents live eu 23 americas 89 western pacific 28 eastern mediterranean 03 south eastern asia 75 respondents pwms five research questions answered highest priority question q 1 mri help predict disability worsening pwms 199 q5 benefits harms treating pwms one diseasemodifying drug compared another 193 q3 multidisciplinary care teams different social health professionals improve health outcomes experiences pwms 119 q16 psychological health affect disease progression pwms 92 q10 benefits harms exercise pwms 72 multivariable logistic regression analysis indicated significant influence geographic area income level ranking q1 marginal q16 top priority accounting effect predictors approximately 50 respondents indicated important additional suggestion consideredconclusionthis international collaborative initiative field ms offers worldwide perspective research questions perceived pivotal geographically representative sample multiple stakeholders field ms results survey guide prioritization research pharmacological nonpharmacological interventions meaningful useful pwms carers avoiding duplication efforts research waste high quality systematic reviews elicited priority setting exercises may offer best available evidence inform decisions healthcare providers policymakers can adapted different realities around world,0.0
covid19 increase longterm relapsingremitting multiple sclerosis clinical activity cohort study background current evidence pointing towards association covid19 worsening multiple sclerosis ms stressing importance preventing covid19 among people ms pwms however populationbased evidence regarding longterm postcovid19 course relapsingremitting multiple sclerosis rrms limited study initiatedobjectiveto detect possible changes ms clinical disease activity covid19methodswe conducted observational study july 2020 july 2021 isfahan ms clinic comparing trends probable disability progression pdp defined threemonth sustained increase expanded disability status scale edss score relapses probable definitive covid19 diagnosis cohort people rrms pwrrms resultsninety pwrrms identified definitive covid19 53 included final analysis pdp rate significantly 006 vs 019 p 004 relapse rate insignificantly 021 vs 030 p 030 lower postcovid19 compared precovid19 period results maintained offsetting followup period matched binary logistic model survival analysis indicate significant difference pdpfree hazard ratio hr 95 ci 046 012 173 p 025 relapsefree hr 95 ci 069 031 153 p 036 survivals pre postcovid19 periods sensitivity analysis resulted similar measurements although statistical significance achievedconclusionwhile subject replication future research settings results confirm increase longterm clinical disease activity measures covid19 contraction among pwrrms,0.0
polymorphisms mutations ace2andtmprss2genesare associated covid19asystematicreview abstractobjectiveto determine effect polymorphisms mutations angiotensinconverting enzyme 2 ace2 type 2 transmembrane serine proteases tmprss2 genes susceptibility corona virus disease 2019 covid19 patient prognosisintroductionfrom december 2019 current time outbreak epidemic covid19 characterized severe acute respiratory syndrome coronavirus 2 sarscov2 occurred around world now clear sarscov2 binds human ace2 receptors expression receptors correlated rate sarscov2 infection mortality polymorphisms individual patient factors ace2 tmprss2 genes linked increase negative outcomes although evidence affirm remains debatablemethodshere performed systematic review based guidelines preferred reporting items systematic reviews metaanalyses prisma criteria aim assessing whether polymorphisms ace2 tmprss2 genes affect covid19 condition extensively searched pubmed medline embase cochrane library web science databases relevant articles reports published english december 2019 december 2021resultsa total 495 fulltext articles downloaded 185 excluded preliminary examination duplicates finally 310 articles evaluated reading titles abstracts 208 eliminated based selection criteria finally 33 articles met inclusion criteria included final assessment genetic data 33 923 patients covid19 drawn general population deriving 160 regions 50 countries well approximately 560 000 samples globalpublic genetic databases included analysis ultimately identified 10 snps 21 mutations ace2 gene along 13 snps 12 variants tmprss2 gene may associated covid19conclusionsace2 tmprss2 play vital roles onset development prognosis sarscov2 infection strongly associated vulnerability intensity clinical result covid19 overall genetic factors may potential future development personalized drugs vaccines covid19trial registration crd42021239400 prospero 2021,0.0
temporal incidence prevalence trends multiple sclerosis markazi province iran abstractbackgroundthe epidemiology multiple sclerosis ms exhibits significant variability world additionally incidence prevalence disease geographically diverse different provinces iranobjectivesdue lack research epidemiology ms markazi province iran present study aimed estimate prevalence incidence provincemethodsthis crosssectional register study conducted according data related ms society markazi province inclusion criteria definite ms 20102019 residence markazi province membership ms society markazi province annual incidence prevalence ms per 100 000 personyears computed sex age groups agestandardized prevalence incidence rates calculated based iranian population gamma regression model log link utilized comparing rates time statistically prevalence incidence rates computed using excel r 405 applied fit gamma modelresultsin study total number ms cases 1 391 among 1 098 789 293 211 females males respectively onset ms occurred mean sd age 3176 898 years female male ratio 375 study period 20102019 incidence rate disease decline prevalence rate elevated indicating rising trend ms prevalence sexesconclusionthe results represented decreasing increasing trend incidence prevalence ms markazi province recent years province one regions high prevalence incidence rate ms compared national global statistical data,0.0
exosomal lncrna tug1 cancerassociated fibroblasts promotes liver cancer cell migration invasion glycolysis regulating mir5245p#x2f six1 axis background increasing evidence suggests taurine upregulated gene 1 tug1 crucial tumor progression however role hepatocellular carcinoma hcc underlying mechanisms well characterizedmethodsthe expression levels tug1 mir5245p sine oculis homeobox homolog 1 six1 determined using quantitative realtime pcr regulatory relationships confirmed dualluciferase reporter assay cell proliferation invasion assessed using cell counting kit 8 transwell assays glucose uptake cellular levels lactate lactate dehydrogenase ldh adenosine triphosphate atp detected using commercially available kits silencing tug1 six1 performed lentivirus transduction protein levels measured immunoblottingresultscancerassociated fibroblasts cafs secreted exosomes promoted migration invasion glycolysis hepg2 cells releasing tug1 promotive effects cafssecreted exosomes attenuated silencing tug1 tug1 six1 targets mir5245p six1 knockdown inhibited promotive effects mir5245p inhibitor silencing tug1 suppressed tumor growth lung metastasis therefore increased survival xenograft model mice also found tug1 six1 increased hcc patients metastasis mir5245p decreased hcc patients metastasisconclusionscafsderived exosomal tug1 promoted migration invasion glycolysis hcc cells via mir5245p six1 axis findings may help establish foundation development therapeutics strategies clinical management hcc future,0.0
a2a adenosine receptor antagonists potential neurological disorders curr med chem 2022 feb 18 doi 102174 0929867329666220218094501 online ahead printabstractendogenous nucleoside adenosine modulates number physiological effects interaction p1 purinergic receptors g protein coupled receptors date four subtypes characterized named a1 a2a a2b a3 recent years adenosine receptors particularly a2a subtype become attractive targets treatment several neurodegenerative disorders known involve neuroinflammation like parkinsons alzheimers diseases multiple sclerosis neuropsychiatric conditions fact demonstrated inhibition a2a adenosine receptors exerts neuroprotective effects counteracting neuroinflammatory processes astroglial microglial activation a2a adenosine receptor antagonist istradefylline developed kyowa hakko kirin inc approved japan adjunctive therapy treatment parkinsons disease recently approved also us food drug administration findings pave way new therapeutic opportunities review summary relevant promising a2a adenosine receptor antagonists will presented along preclinical clinical studies neuroinflammation related diseasespmid35184706 doi102174 0929867329666220218094501,1.0
stem cells human exfoliated deciduous teethconditioned medium shedcm promising treatment amyotrophic lateral sclerosis front pharmacol 2022 feb 3 13805379 doi 103389 fphar2022805379 ecollection 2022abstractamyotrophic lateral sclerosis als neurodegenerative disorder characterized loss upper lower motor neurons effective treatment yet developed previous reports shown excessive oxidative stress related mitochondrial dysfunction accumulation misfolding protein contributes als pathology terms treatment remains necessary identify effective medicines multiple therapeutic targets additive effects several disorders study investigated stem cells human exfoliated deciduous teeth shed release many factors neurotrophic factors cytokines applied treat neurological diseases specifically examined whether shedconditioned medium cm ie serumfree culture supernatant shed reduced mutant sod1induced intracellular aggregates neurotoxicity found shedcm significantly suppressed mutant sod1induced intracellular aggregates neurotoxicity neuroprotective effects shedcm partly related heat shock protein activation insulinlike growth factor1 receptor shedcm also protective effect induced pluripotent stem cellderived motor neurons moreover shedcm effective familial als also sporadic als overall results suggest shedcm promising treatment slowing progression alspmid35185565 pmcpmc8850386 doi103389 fphar2022805379,1.0
sexspecific environmental impacts initiation progression multiple sclerosis front neurol 2022 feb 3 13835162 doi 103389 fneur2022835162 ecollection 2022abstractthe immunological mechanisms contribute multiple sclerosis ms differ males females females 23 times likely develop ms compared males however reason discrepancy unknown ms established inflammatory yet milder form disease females whereas males generally suffer severe disease faster progression neural degradation disability differences relate genetics including genetic control immune regulatory genes xchromosome well immune modulatory properties sex hormones differences ms development may also relate sex interacts environmental risk factors several environmental risk factors ms including lateonset epstein barr virus infection low serum vitamin d levels low uv radiation exposure smoking obesity lack physical activity risk factors impact males females differently either due biological immunological processes behavioral differences review explore differences focus interaction environmental risk factors sex hormones may contribute significantly different prevalence pathology ms males femalespmid35185777 pmcpmc8850837 doi103389 fneur2022835162,0.0
therapeutic opportunities targeting cellular senescence progressive multiple sclerosis curr opin pharmacol 2022 feb 18 63102184 doi 101016 jcoph2022102184 online ahead printabstractrecent studies implicated cellular senescence diseaserelated process linked progressive forms multiple sclerosis ms herein present overview current pharmacopeia cellular senescence affecting compounds evidence effects known murine cellular models ms consideration also given utility compounds treatment progressive ms examination past current clinical trials tested agents often purposes ms patient population lastly discuss implications potential utility targeting cellular senescence strategy fulfil unmet need treatment options progressive ms populationpmid35189476 doi101016 jcoph2022102184,0.0
innate lymphoid cells central nervous system front immunol 2022 feb 3 13837250 doi 103389 fimmu2022837250 ecollection 2022abstractimmune cells present within central nervous system play important roles neurological inflammation disease relatively new described immune cell population innate lymphoid cells now increasingly recognized within central nervous system associated diseases innate lymphoid cells generally regarded tissue resident early responders conversely within central nervous system steadystate presence limited review describes current understandings innate lymphoid cells central nervous system steadystate borders plus involvement major neurological diseases like ischemic stroke alzheimers disease multiple sclerosispmid35185929 pmcpmc8852840 doi103389 fimmu2022837250,0.0
reviewemerging portable technologies gait analysis neurological disorders front hum neurosci 2022 feb 3 16768575 doi 103389 fnhum2022768575 ecollection 2022abstractthe understanding locomotion neurological disorders requires technologies quantitative gait analysis numerous modalities available today objectively capture spatiotemporal gait postural control features nevertheless many obstacles prevent application technologies full potential neurological research especially clinical practice include required expert knowledge time data collection missing standards data analysis reporting provide technological review wearable visionbased portable motion analysis tools emerged last decade recent applications neurological disorders parkinsons disease multiple sclerosis goal enable reader understand available technologies individual strengths limitations order make informed decision investigations clinical applications foresee ongoing developments toward userfriendly automated devices will allow closedloop applications longterm monitoring telemedical consulting reallife environmentspmid35185496 pmcpmc8850274 doi103389 fnhum2022768575,0.0
deformationbased morphometry identifies deep brain structures protected ocrelizumab neuroimage clin 2022 feb 14 34102959 doi 101016 jnicl2022102959 online ahead printabstractbackground despite advancements treatments multiple sclerosis insidious disease progression remains area unmet medical need atrophybased biomarkers may help better characterize progressive biologymethods developed applied method longitudinal deformationbased morphometry provide voxellevel assessments brain volume changes identified brain regions significantly impacted diseasemodifying therapyresults using brain mri data two identically designed pivotal trials relapsing multiple sclerosis total n 1483 identified multiple deep brain regions including thalamus brainstem volume loss time reduced ocrelizumab p 005 humanized anticd20 + monoclonal antibody approved treatment multiple sclerosis additionally identified brainstem shrinkage well brain ventricle expansion associated greater risk confirmed disability progression p 005 conclusions identification deep brain structures strong implication developing new biomarkers brain atrophy reduction advance drug development multiple sclerosis increasing focus targeting progressive biologypmid35189455 doi101016 jnicl2022102959,0.0
regulation activated microglia macrophages systemically administered dna#x2f rna heteroduplex oligonucleotides mol ther 2022 feb 18s15250016 22 001034 doi 101016 jymthe202202019 online ahead printabstractmicroglial activation followed recruitment bloodborne macrophages central nervous system cns aggravates neuroinflammation specifically multiple sclerosis ms well experimental autoimmune encephalomyelitis eae rodent model ms activated microglia macrophages mg m promote proinflammatory responses expand demyelination cns however potent therapeutic approach systemic route regulating functions yet developed demonstrated systemically injected dna rna heteroduplex oligonucleotide hdo composed antisense oligonucleotide aso complementary rna conjugated cholesterol cholhdo distributed efficiently demyelinating lesions spinal cord eae mice significant gene silencing parent aso importantly systemic administration cd40targeting cholhdo improved clinical signs eae significant downregulation cd40 mg m furthermore successfully identified macrophage scavenger receptor 1 msr1 responsible uptake cholhdo mg m eae mice overall findings demonstrate therapeutic potency systemically administered cholhdo regulate activated mg m neuroinflammationpmid35189344 doi101016 jymthe202202019,1.0
effectiveness anticluster differentiation 20 diseasemodifying therapy multiple sclerosis across different phenotypes university hospital caen cureus 2022 feb 11 14 2 e22120 doi 107759 cureus22120 ecollection 2022 febabstractbackground multiple sclerosis chronic demyelinating disorder occurring primarily two main forms relapsingremitting multiple sclerosis rrms found predominantly women primary progressive multiple sclerosis ppms occurring predominantly men retrospective singlecenter study aimed explore effects anticluster differentiation cd 20 treatment relapsingremitting primary progressive forms multiple sclerosis ms populationbased cohort treated university hospital methodology diagnostic factors assessed forms multiple sclerosis ms age first relapse whereas therapeutic factors age first diseasemodifying therapy dmt age starting anticd20 reason switch anticd20 duration anticd20 treatment primary outcomes measured number relapses progression disability measured expanded disability status scale secondary outcomes measures assessed number cerebral lesions mri level igg beginning end 12month treatment results treatment anticd20 demonstrated reduction number relapses 12 months treatment change progression disability rrms type increase ppms type change observed cerebral mri lesions end treatment 12 months statistically significant reduction serum igg value observed 12 months start treatment one 26 38 patients developed hypogammaglobulinemia igg less 6 g l none developed hypogammaglobulinemia less 5 g l conclusion anticd20 antibodies diseasemodifying therapy can profoundly impact course progression ms forms utilized earlier stage patients therefore greatly improve quality life patients living multiple sclerosispmid35186606 pmcpmc8844373 doi107759 cureus22120,1.0
characterization antigeninduced cd4+ tcell senescence multiple sclerosis front neurol 2022 feb 3 13790884 doi 103389 fneur2022790884 ecollection 2022abstractantigeninduced tcell exhaustion tcell senescence peripheral regulatory mechanisms control effector tcell responses markers exhaustion senescence t cells indicate previous activation repetitive stimulation specific antigens malignant tumors accompanied enhanced tcell exhaustion tcell senescence resulting immune evasion control mechanisms might diminished autoimmune diseases including multiple sclerosis ms better understand involvement antigeninduced tcell senescence controlling cd4+ tcellmediated autoimmune responses ms analyzed reexpression cd45ra downregulation cd28 cd27 molecules markers antigeninduced tcell senescence fresh cerebrospinal fluid csf infiltrating paired circulating t cells patients ms patients different levels cd4+ tcell senescence identified characterized regarding demographical clinical features well intrathecal markers neurodegeneration cd4+ tcell senescence also analyzed control patients explore putative deficit regulatory mechanism ms study shows heterogeneity markers cd4+ tcell senescence patients ms patients high levels cd4+ tcell senescence peripheral blood showed increased frequencies csfinfiltrating cd28+ cd27em cd4+ t cells proinflammatory th1 functional phenotype correlation cells intrathecal levels neurofilament light chain marker neurodegeneration suggests relevance disease pathogenesis involvement tcell senescence regulation markers antigeninduced tsenescence therefore show promise tool identify pathogenic cd4+ t cells patients mspmid35185762 pmcpmc8852676 doi103389 fneur2022790884,0.0
determination csf gfap ccn5 vwf levels enhances diagnostic accuracy clinically defined ms nonms patients csf oligoclonal bands front immunol 2022 feb 4 12811351 doi 103389 fimmu2021811351 ecollection 2021abstractbackground inclusion cerebrospinal fluid csf oligoclonal igg bands ocgb revised mcdonald criteria increases sensitivity diagnosis dissemination time dit proven ocgb negative patients unlikely develop clinically definite cd ms ocgb positivity may lead erroneous diagnosis conditions present similarly neuromyelitis optica spectrum disorders nmosd neurosarcoidosisobjective identify specific ocgbcomplementary biomarkers improve diagnostic accuracy ocgb positive patientsmethods analysed csf metabolome proteome cdms n41 confirmed nonms patients n64 comprising range cns conditions routinely encountered neurology clinicsresults ocgb discriminated cdms nonms high sensitivity 85 low specificity 67 previously described machine learning methods revealed ccn5 levels provide greater accuracy sensitivity specificity ocgb 79 +5 90 +5 72 +5 respectively glial fibrillary acidic protein gfap identified cdms 100 specificity +33 multiomics approach improved accuracy 90 +16 conclusion measurement additional csf biomarkers used complement ocgb improve specificity ms diagnosis clinical radiological evidence dit absentpmid35185866 pmcpmc8855362 doi103389 fimmu2021811351,0.0
spontaneous model experimental autoimmune encephalomyelitis provides evidence mogspecific b cell recruitment clonal expansion front immunol 2022 feb 3 13755900 doi 103389 fimmu2022755900 ecollection 2022abstractthe key role b cells pathophysiology multiple sclerosis ms supported presence oligoclonal bands cerebrospinal fluid association meningeal ectopic b cell follicles demyelination axonal loss reduction astrocytes well high efficacy b lymphocyte depletion controlling inflammatory parameters ms use spontaneous model experimental autoimmune encephalomyelitis eae study clonality b cell response targeting myelin oligodendrocyte glycoprotein mog particular 94 sjl j mice expressing ias mog92106 specific transgenic t cell receptor tcr1640 spontaneously develop chronic paralytic eae age 60500 days immune response triggered microbiota gutassociated lymphoid tissue evidence maturation autoimmune demyelinating response might occur cervical lymph nodes owing local brain drainage using mogproteintetramers tracked autoantigenspecific b cells localized enrichment cervical lymph nodes among brain immune infiltrate mogspecific igg1 antibodies detected serum diseased tcr1640 mice proved pathogenic upon adoptive transfer diseaseprone recipients ontogeny mogspecific humoral response preceded disease onset coherent contribution eae initiation humoral response however sufficient disease induction mogantibodies detected age 69 days model average age onset 197 days assess mogspecific b cell repertoire facssorted mogtetramer binding cells clonally expand vitro sequence paratopes igg heavy chain kappa light chains despite fragility clonally expanding mogtetramer binding effector b cells results indicate selection common cdr3 clonotype among igk light chains derived diseasefree diseased tcr1640 mice study demonstrates preclinical mobilization mogspecific b cell response within braindraining cervical lymph nodes reiterates mog antibodies poor biomarker disease onset progressionpmid35185870 pmcpmc8850296 doi103389 fimmu2022755900,1.0
progesterone inhibits establishment activationassociated chromatin th1 differentiation front immunol 2022 feb 2 13835625 doi 103389 fimmu2022835625 ecollection 2022abstractth1mediated diseases multiple sclerosis ms rheumatoid arthritis ra improve pregnancy coinciding increasing levels pregnancy hormone progesterone p4 highlighting p4 potential mediator immunomodulation performed detailed characterization p4 affects chromatin transcriptomic landscape early human th1 differentiation utilizing atacseq rnaseq time series analysis earlier events 0524 hrs th1 differentiation revealed p4 counteracted many changes induced normal differentiation mainly downregulating key regulatory genes upstream transcription factors tfs involved initial tcell activation members ap1 complex fosl1 fosl2 jun junb particularly affected promoters distal regulatory elements moreover changes induced p4 significantly enriched diseaseassociated changes related ms ra revealing several shared upstream tfs jun highlighted central importance findings support immune regulatory role p4 pregnancy impeding tcell activation crucial checkpoint pregnancy tcell mediated diseases central event prior tcell lineage commitment indeed p4 emerging likely candidate involved disease modulation pregnancy studies evaluating p4 potential treatment option neededpmid35185927 pmcpmc8848251 doi103389 fimmu2022835625,0.0
systematic review safety efficacy second thirdgeneration cd20targeting biologics treating immunemediated disorders front immunol 2022 feb 2 12788830 doi 103389 fimmu2021788830 ecollection 2021abstractbackground b cells can contribute immunemediated disorders targeting cd20 proved efficacious several b cellmediated immunopathologies illustrated use rituximab first anticd20 monoclonal antibody mab following rituximab second thirdgeneration anticd20 mabs developed tried immunemediated diseases including obinutuzumab ocrelizumab ofatumumab ublituximab veltuzumab however safety efficacy systematically reviewedobjective evaluate safety efficacy obinutuzumab ocrelizumab ofatumumab ublituximab veltuzumab treatment immunemediated disorders compared placebo conventional treatment biologicsmethods prisma checklist guided reporting data searched pubmed database 4 october 2016 22 july 2021 concentrating immunemediated disordersresults literature search identified 2220 articles screening titles abstracts inclusion exclusion criteria assessing full texts 27 articles finally included narrative synthesisconclusions obinutuzumab shown promising results case series patients phospholipase a2 receptorassociated membranous nephropathy mixed results systemic lupus erythematosus ocrelizumab approved use patients relapsingremitting multiple sclerosis primary progressive multiple sclerosis ocrelizumab also tested patients rheumatoid arthritis demonstrating promising results systemic lupus erythematosus revealing mixed results however conditions use associated increased risk serious infections ofatumumab received approval treating patients relapsingremitting multiple sclerosis moreover ofatumumab showed promising results patients antineutrophil cytoplasmic antibodyassociated vasculitis rheumatoid arthritis systemic lupus erythematosus well mixed results phospholipase a2 receptorassociated membranous nephropathy ublituximab assessed relapsingremitting multiple sclerosis neuromyelitis optica spectrum disorder promising results however included number patients small conclude veltuzumab tested patients immune thrombocytopenia resulting improved platelet countssystematic review registration https wwwcrdyorkacuk prospero identifier crd4201913421pmid35185862 pmcpmc8847774 doi103389 fimmu2021788830,0.0
quantitative mri findings indicate diffuse white matter damage susac syndrome mult scler j exp transl clin 2022 feb 14 8 1 20552173221078834 doi 101177 20552173221078834 ecollection 2022 janmarabstractbackground susac syndrome sus autoimmune endotheliopathy impacting brain retina cochlea can clinically mimic multiple sclerosis ms objective evaluate nonlesional white matter demyelination changes sus compared ms healthy controls hc using quantitative mrimethods 3t mri including myelin water imaging diffusion basis spectrum imaging acquired 7 sus 10 ms 10 hc participants nonlesional white matter analyzed corpus callosum cc normal appearing white matter nawm groups compared using ancova tukey correctionresults sus cc myelin water fraction mean 0092 lower ms 011 p 001 hc 011 p 004 another myelin marker radial diffusivity increased sus cc 027m2 ms compared hc 021m2 ms p 0008 ms 023m2 ms p 005 fractional anisotropy lower sus cc 082 hc 086 p 004 fiber fraction reflecting axons differ hc ms nawm radial diffusivity apparent diffusion coefficient significantly increased sus compared hc p 0001 measures ms p 0003 p 0001 respectively conclusions results provided evidence myelin damage sus particularly cc extensive microstructural injury nawm supporting hypothesis widespread microstructural changes sus syndrome including diffuse demyelinationpmid35186315 pmcpmc8851927 doi101177 20552173221078834,1.0
gut oraldysbiosis differentially impact spinal bulbaronset als predicting als severity potentially determining location disease onset background prior studies role gutmicrobiome amyotrophic lateral sclerosis als pathogenesis yielded conflicting results hypothesized gut oralmicrobiome may differentially impact two clinicallydistinct als subtypes spinalonset als sals vs bulbaronset als bals driving disagreement fieldmethodsals patients diagnosed within 12 months spouses healthy controls n 150 couples screened eligible sals bals patients n 36 healthy controls n 20 16s rrna nextgeneration sequencing done fecal saliva samples dna extractions examine gut oralmicrobiome differences microbial translocation blood measured blood lipopolysaccharidebinding protein lbp 16s rdna levels als severity assessed revised als functional rating scale alsfrsr resultssals patients manifested significant gutdysbiosis primarily driven increased fecal firmicutes bacteroidetesratio f bratio contrast bals patients displayed significant oraldysbiosis primarily driven decreased oral f bratio sals patients gutdysbiosis shift fecal f bratio oraldysbiosis strongly associated greater microbial translocation blood r 08006 p 00001 severe symptoms r 09470 p 00001 contrast bals patients oraldysbiosis shift oral f bratio gutdysbiosis strongly associated greater microbial translocation blood r 09860 p 00001 greater disease severity r 09842 p 00001 als subtypes greater microbial translocation associated severe symptoms sals r 07924 p 00001 bals r 07496 p 00067 importantly sals bals patients displayed comparable oralmotor deficits associations oraldysbiosis severity oralmotor deficits bals sals suggests oraldysbiosis simply caused oral bulbar respiratory symptoms represents pathological driver balsconclusionswe found increasing gutdysbiosis worsening symptoms sals patients increasing oraldysbiosis worsening symptoms bals patients findings support distinct microbial mechanisms underlying two als subtypes previously grouped together single disease study suggests correcting gutdysbiosis therapeutic strategy sals patients correcting oraldysbiosis therapeutic strategy bals patients,0.0
chinese expert recommendations ketogenic diet therapy superrefractory status epilepticus abstractsuperrefractory status epilepticus srse serious lifethreatening neurological condition ketogenic diet kd diet characterized high fat low carbohydrate moderate protein kd shows effectiveness controlling seizures half srse patients can treatment option srse currently kd treatment srse based personal experience observational evidence published context lack validated guideline convened multicenter expert panel within china association epilepsy caae ketogenic diet commission work chinese expert recommendations kd srse summarize discuss latest clinical practice kd srse critical care settings recommendations given patient selection timing kd diet implementation followup research data needed area support better clinical practice,0.0
ginkgo biloba leaf extract mitigates cisplatininduced chronic renal interstitial fibrosis inhibiting epithelialmesenchymal transition renal tubular epithelial cells mediated smad3#x2f tgf1 smad3#x2f p38 mapk pathways background previous study indicated ginkgo biloba leaf extract egb protect cisplatininduced acute kidney injury rabbits present study aimed determine effects potential molecular mechanisms egb chronic renal interstitial fibrosis induced cisplatin using vivo vitro modelsmethodsrats received single dose cisplatin day 1 subset rats intraperitoneally injected egb daily days 2240 vitro hk2 cells treated cisplatin subset cells cultivated egb sis3 smad3 inhibitor 48 h renal function rats assessed detecting levels serum creatinine scr blood urea nitrogen bun urinary nacetyldglucosaminidase nag hematoxylin eosin staining massons trichrome staining used evaluate damage fibrosis renal tissue western blotting immunohistochemistry immunofluorescence used detect protein levels fibrosisassociated proteins signaling pathwayrelated proteins rtqpcr analysis used examine mrna levels related indicatorsresultsegb significantly decreased increased levels scr bun urinary nag attenuated renal damage relative area renal interstitial fibrosis induced cisplatin additionally egb decreased protein levels sma col tgf1 smad2 3 phosphorylated p smad2 3 p38 mapk pp38 mapk ratio pp38 mapk p38 mapk mrna level p38 mapk renal tissues induced cisplatin agreement vivo studies egb significantly reduced increased protein levels indicators additionally egb significantly reduced increased protein levels vimentin timp1 ctgf well mrna levels sma vimentin tgf1 significantly increased reduced ecadherin protein level mmp1 timp1 ratio hk2 cells induced cisplatin worth noting effects sis3 changing indicators similar egbconclusionour study demonstrated egb improved cisplatininduced chronic renal interstitial fibrosis mechanisms associated inhibiting epithelialmesenchymal transition renal tubular epithelial cells via smad3 tgf1 smad3 p38 mapk pathways,0.0
two stools preclinical research reproducibility statistical design experiments abstracttranslation animalbased preclinical research hampered poor validity reproducibility issues unfortunately preclinical research fallen stools competing study design traditions preclinical studies often characterised small sample sizes large variability problem data although fishertype designs randomisation blocking appropriate vigorously promoted structured statisticallybased designs almost unknown traditional analysis methods commonly misapplied basic terminology principles inference testing misinterpreted problems compounded lack adequate statistical training researchers failure statistical educators account unique demands preclinical research solution return basics statistical education tailored nonstatistician investigators clear communication statistical concepts curricula address design data issues specific preclinical research statistics curricula focus statistics process data sampling study design analysis inference properlydesigned analysed experiments matter ethics much procedure shifting focus statistical education rote hypothesis testing sound methodology will reduce numbers animals wasted noninformative experiments increase overall scientific quality value published research,0.0
safety sinopharm vaccine people multiple sclerosis study adverse reactions disease activity abstractbackground aim study evaluate safety sinofarm vaccine bbibpcorv patients multiple sclerosis pwms methods study conducted pwms patients isfahan iran participants received two doses bbibpcorv sinopharm vaccine demographic information data vaccine side effects collected dose using questionnaires patients recorded worsening ms symptoms evaluated true relapse treated iv methyl prednisoloneresults 1538 patients 1151 748 female mean age 4045 974 average disease duration 1038681 years 761 participants rrms 928 participants using dmts mean edss 206 316 542 833 patient reported least one adverse event first dose vaccine 468 720 patient second dose cases going away days prevalent adverse events doses injection site pain headache myalgia fever fatigue adverse events prevalent younger less prevalent mildly disabled patients seven cases covid19 infection first second vaccination dose eight cases onemonth follow second dose none needed mechanical ventilation ten patients first dose thirteen patients second dose experienced acute relapse patient two relapses one vaccine dose clinically radiologically confirmed first relapse occurred seven days first vaccination hemiparesis relapse 14 days second dose diplopia hemiparesis ataxiaconclusion adverse events pwms following vaccination sinopharm vaccine similar general population common younger patients less common mild disability increase relapse rate vaccination detected sinopharm vaccine safe ms patients,0.0
discovery novel potent inhibitor differential speciesspecific effects nlrp3 aim2 inflammasomedependent pyroptosis eur j med chem 2022 feb 11 232114194 doi 101016 jejmech2022114194 online ahead printabstractthe nlrp3 inflammasome regulated proinflammatory programmed cell death form termed pyroptosis involved pathological process various human diseases multiple sclerosis type 2 diabetes gout thus compounds inhibiting activation nlrp3 inflammasome can promising treatments diseases study conducted phenotypic screening nlrp3dependent pyroptosis discovered hit compound 1 showed moderate antipyroptotic activity chemistry efforts improve potency 1 resulted novel compound 59 j114 exhibited halfmaximal inhibitory concentration ic50 0077 0008 m cell pyroptosis interestingly unlike pyroptosis inhibitors currently reported activity j114 showed significant differences human mousederived cells ic50 j114mediated inhibition il1 secretion human thp1 macrophages 0098 m nearly 150fold 500fold potent j774a1 1462 m bone marrowderived macrophages bmdms 4898 m respectively studies showed j114 displayed remarkable inhibitory activity nlrp3 aim2but nlrc4dependent activation caspase1 release il1 human thp1 macrophages mechanistically j114 disturbed interaction nlrp3 aim2 adaptor protein asc inhibited asc oligomerization overall study identified unique molecule inhibits nlrp3 aim2 inflammasome activation species differences worthy research understand differential regulation nlrp3 aim2 inflammasomes humans micepmid35183871 doi101016 jejmech2022114194,0.0
coupling brain activity structural network multiple sclerosis graph frequency analysis study j neurosci res 2022 feb 20 doi 101002 jnr25028 online ahead printabstractthe brain activities underlying wiring diagrams vulnerable multiple sclerosis ms also remains unknown whether complex coupling functional structural brain properties affected address issue adopted graph frequency analysis quantify highorder structuralfunctional interactions based combination brain diffusion functional mri data structuralfunctional decoupling index proposed measure much brain regional functional activity different graph frequency organized atop underlying wiring diagram ms identified patterns ms included 1 disruption inherent structuralfunctional coupling somatomotor network 005 p 003 2 excessive decrease decoupling subcortical 010 p 002 visual 004 p 001 dorsal attention networks 012 p 003 besides structuralfunctional coupling signature somatomotor network associated cognitive worsening ms patients 2431 p 0006 overall study unveiled unique signature brain structuralfunctional reorganization mspmid35184336 doi101002 jnr25028,0.0
expression pattern vista pbmcs relapsingremitting multiple sclerosis patients singlecell rna sequencingbased study biomed pharmacother 2022 feb 17 148112725 doi 101016 jbiopha2022112725 online ahead printabstractmultiple sclerosis ms inflammatory disease central nervous system cns dysregulated immune responses implicated ms development growing evidence indicated inhibitory immune checkpoint molecules can substantially regulate immune responses maintain immune tolerance vdomain ig suppressor t cell activation vista novel inhibitory immune checkpoint molecule can suppress immune responses however expression pattern peripheral blood mononuclear cells pbmcs relapsingremitting multiple sclerosis rrms thoroughly studied herein evaluated vsir expression pbmcs rrms patients characterized expression pattern vsir pbmcs ms patients besides investigated effect fingolimod ifn1 glatiramer acetate ga dimethyl fumarate dmf vsir expression pbmcs rrms patients results shown vsir expression significantly downregulated pbmcs patients rrms besides singlecell rna sequencing results demonstrated vsir expression downregulated classical monocyte intermediate monocytes nonclassical monocytes myeloid dcs mdc plasmacytoid dendritic cells pdcs naive bcells pbmcs ms patients compared control addition dmf ifn1 ga significantly upregulated vsir expression pbmcs rrms patients collectively current study shed light vsir expression pbmcs ms patients however studies needed elucidate significance vista mentioned immune cellspmid35183994 doi101016 jbiopha2022112725,0.0
developing tools evaluate quality care management patients living multiple sclerosis original french initiative rev neurol paris 2022 feb 16s00353787 22 001631 doi 101016 jneurol202112011 online ahead printabstractintroduction assessing quality care management patients chronic disease multiple sclerosis ms major challenge healthcare systems around world needs carried using tools recognized professionals patients alike concern practices systems scientific data tools currently available europe purpose present study develop indicators contribute assess quality care management patients ms francemethods expert panel comprising 25 professionals well known teams across france selected indicators basis consensus accordance rand ucla appropriateness method expert agree recommendations agreement among expertsresults expert panel selected 48 indicators representing seven domains care management patients ms physical rehabilitation medicine disease progression access care magnetic resonance imaging mri management relapse management management diseasemodifying treatments management symptoms disability progression quality indicators notably pertaining mri management previously identified literatureconclusion indicators may allow professionals comprehensively assess compare practices cooperation thereby contributing improve quality care management patients ms francepmid35183366 doi101016 jneurol202112011,0.0
realworld diseasemodifying therapy usage persons relapsingremitting multiple sclerosis crosssectional data swiss multiple sclerosis registry introductionseveral diseasemodifying therapies dmts covering broad spectrum mechanisms action approved regulatory agencies treatment relapsingremitting multiple sclerosis rrms however little known current realworld treatment situation switzerland based data diverse population 668 persons rrms swiss multiple sclerosis registry smsr present study aims fill gap descriptive crosssectional approachmethodsdata originated smsr baseline questionnaire followup surveys data current health status life situation last 6 months extracted survey distributed throughout 2020 2021 data diseasemodifying therapy dmt histories included preceding surveys initially data stratified three dmt groups according current dmt status dmt continued dmt started 6 months ago new dmt started less 6 months ago subsequent analysis sample stratified groups corresponding five frequently prescribed dmts selfreported outcomes including therapy discontinuation interruption relapses sideeffects last 6 months analyzed per group life health situation parameters also determined analyzedresultsthe study population consisted 445 666 individuals belonging continued 84 126 new 139 208 group within group 24 173 reported relapses furthermore selfreported relapses 28 333 sideeffects 39 464 treatment discontinuations interruptions 30 357 occurred frequently new compared continued group 37 83 125 281 8 18 respectively three groups also differed respect age time since diagnosis number symptoms dmt history healthrelated quality life five frequently prescribed dmts included fingolimod 334 dimethyl fumarate 250 ocrelizumab 236 natalizumab 106 teriflunomide 75 frequency selfreported relapses ranged 97 136 notable differences found number selfreported sideeffects ranging 91 natalizumab 567 dimethyl fumaratediscussionthis crosssectional analysis suggested majority individuals rrms switzerland continuously receive tolerable dmt however groups receiving dmt struggling sideeffects continued disease worsening dmt still persist conceivable number selfreported symptoms indicates need detailed clarification dmt characteristics expectations treatment outcomes injectable dmts longer play major role treatment rrms switzerland trend toward early use potent drugs emerging,0.0
prospective associations better quality diet improved quality life 75 years people multiple sclerosis abstractbackground increasing interest role diet multiple sclerosis ms progression whether healthier diet may lead improved health wellbeing people living ms plwms objective assess prospective relationship quality dietary intakes quality life qol international cohort plwms followed 75 yearsmethods data health outcomes lifestyle sample people multiple sclerosis holism cohort baseline 75year review analysed quality diet assessed using diet habits questionnaire dhq qol measured msqol54 including physical mental health composite scores multiple subdomains linear regression used determine crosssectional prospective relationships qol adjusted clinical demographic covariatesresults amongst 948 participants median physical mentalhealth qol scores 75year review 669 782 respectively baseline total dhq positively associated subsequent change physicalqol 75year review participants top two quartiles baseline dhq 065 064 higher physicalqol per year though similar association mentalqol persist adjustment baseline meat consumption associated 038 lower physicalqol baseline dairy consumption associated 050 041 lower physical mentalqol per year respectivelyconclusions results suggest efforts improve quality dietary intake beneficial wellbeing plwms subject replication aspect lifestyle useful intervention better managing ms,0.0
measuring cognitive function sdmt across functional domains useful sufficient abstractbackgroundthe symbol digit modalities test sdmt common screen cognitive function people multiple sclerosis pwms growing acknowledgement people cognitive impairment heterogeneous population suggests single screen may provide limited informationobjectiveto assess adequacy sdmt capturing impairment across specific cognitive domains measured multidomain cognitive assessment battery cab neurotrax methods113 pwms assessed sdmt cab cognitive impairment cab domain defined 15 sd normalized mean logistic regression models fit cab domain domainspecific cognitive impairment outcome sdmt predictor classifier created selecting cutpoints using youden index model performance assessed predicting domainspecific cognitive impairment independent data set consisting 81 pwmsresultssdmt significant predictor cognitive impairment outcomes considered odds ratio 08850950 prediction metrics area receiver operating curve auc modest 06230778 alignment observed predicted impairment less optimalconclusionthe sdmt sufficient differentiate impaired nonimpaired pwms across several cognitive domains,0.0
reduced cognitive function contributes economic burden multiple sclerosis abstractbackgroundcognitive impairment common symptom multiple sclerosis ms effect cognitive impairment people ms employment quality life mental health known however studies investigated cognitive deficits contribute economic burden msobjectiveto investigate cognitive impairment correlates economic burden msmethodsthe client service receipt inventory used determine cost healthcare system participant pocket cost community cost total societal cost quality life evaluated using euroqol participants cognitive performance assessed audio recorded cognitive screen symbol digit modalities test spearmannulls rank correlation coefficient r used gauge strength correlation domain scores cost metricsresultsmemory speed writing symbol digit modalities test negatively correlated aspects cost care r024059 p05 found independent factors edss mental health indicesconclusioncognitive deficits independently correlated economic burden ms monitored part routine care,0.0
aquatic exercise persons ms patientreported preferences obstacles recommendations abstractbackground many persons multiple sclerosis ms difficulties engaging traditional landbased physical activity due heat sensitivity physical disability aquatic exercise may suitable alternative individuals preventing overheating enabling range movements otherwise difficult land objective current study understand persons ms prefer aquatic exercise others prefer nonaquatic exercise will inform recommendationsmethods total 179 persons ms completed brief online survey 10 minutes exercise routines october 2020 april 2021results fiftysex percent respondents reported engaged nonaquatic exercise ie landbased activities jogging followed 36 respondents reported engaged aquatic nonaquatic exercise 7 respondents participated aquatic exercise frequently reported barriers aquatic exercise lack access pools associated expense among individuals tried aquatic exercise aquatic exercise preferred nonaquatic exercise 100 reported recommend aquatic exercise persons ms finally majority respondents reported exercising less coronavirus disease 2019 covid19 pandemicconclusion aquatic exercise well liked among persons ms tried however may feasible economically disadvantaged persons ms local charities health organizations may consider financially sponsoring aquatic exercise programs encourage participation physical activity ms population due negative impact pandemic exercise routines ms clinicians encourage patients resume exercise routines pandemic subsides,0.0
peginterferon beta1a concentrations breast milk lactating multiple sclerosis patients abstractbackgroundpeginterferon beta1a interferon beta1a formulation pegylated resulting longer halflife interferon beta formulations examined concentrations peginterferon beta1a breast milk lactating patients multiple sclerosis ms receiving peginterferon beta1a postpartum diseasemodifying therapymethodsafter completion titration full dose peginterferon beta1a following single full dose peginterferon beta1a injection 125 g breast milk samples 10 ml collected 5 women days 114 post injection peginterferon beta1a concentrations breast milk samples measured qualified enzymelinked immunosorbent assay detection threshold 15 pg ml mean median daily concentrations median maximum concentration cmax time cmax tmax time last measurable concentration tlast area concentrationtime curve auclast relative infant dose rid determinedresultsafter receiving single full dose peginterferon beta1a injection maximum breast milk concentration recorded individual patient 1262 pg ml 000013 g ml day 6 remaining patients maximum breast milk concentrations 72 pg ml geometric mean cmax 489 pg ml median tmax tlast 4 7 days respectively median auclast 2109 daypg ml among 5 study patients mean breast milk concentration across study days 3595 pg ml estimated rid 00054 maternal doseconclusionminimal concentrations peginterferon beta1a detected breast milk samples findings may useful clinicians considering postpartum ms treatment options,0.0
physical activity cardiorespiratory fitness subcortical brain structures explain reduced walking performance older adults multiple sclerosis abstractbackground adults multiple sclerosis ms age walking speed endurance progressively decline yet limited understanding factors explain agerelated declines current study examined subcortical brain structures cardiorespiratory fitness moderatetovigorous physical activity mvpa explanations reduced walking performance older adults msmethods older adults ms n29 62858 years ageandsex matched controls n28 63855 years completed measures walking speed timed25ft walk walking endurance sixminute walk cardiorespiratory fitness devicemeasured mvpa underwent mri provide composite volumes thalamus caudate putamen pallidum used mediator variable framework describe group differences determine correlations overall sample identify variables explain reduced walking performanceresults compared controls older adults ms worse walking speed p0001 endurance p0001 lower fitness p004 lower levels mvpa p0001 smaller composite volumes thalamus p0001 putamen p004 pallidum p0007 overall sample measures walking performance significantly correlated fitness mvpa volumes thalamus putamen r range 034065 regression analyses indicated mvpa 0007094 partially explained group differences walking speed fitness 77640 mvpa 175797 partially explained group differences walking enduranceconclusions collectively results suggest cardiorespiratory fitness mvpa subcortical brain structures may modifiable targets future interventions improving walking older adults ms,1.0
factors supporting availability homebased neuromodulation using remote supervision middleincome countries brazil experience brain stimul 2022 feb 15s1935861x 22 00033x doi 101016 jbrs202202005 online ahead printno abstractpmid35181531 doi101016 jbrs202202005,0.0
evolution antib cell therapeutics autoimmune neurological diseases neurotherapeutics 2022 feb 18 doi 101007 s1331102201196w online ahead printabstractb cells everincreasing role etiopathology number autoimmune neurological disorders acting antigenpresenting cells facilitating antibody production also sensors coordinators regulators immune response particular b cells can regulate t cell activation process participation antigen presentation production proinflammatory cytokines bystander activation suppression contribution ectopic lymphoid aggregates important interplay b t cells makes therapeutic depletion b cells attractive treatment strategy last decade antib cell therapies using monoclonal antibodies b cell surface molecules evolved rational approach successfully treating autoimmune neurological disorders even t cells seem main effector cells paper summarizes basic aspects b cell biology discusses roles b cells neurological autoimmunities highlights currently available development antib cell therapeutics exert action wide spectrum immunologically diverse neurological disorders efficacy various antib cell therapies practical issues induction maintenance therapy specifically detailed treatment patients multiple sclerosis neuromyelitisspectrum disorders autoimmune encephalitis hyperexcitability cns disorders autoimmune neuropathies myasthenia gravis inflammatory myopathies success antib cell therapies inducing longterm remission igg4 neuroautoimmunities also highlighted pointing potential biomarkers followup infusionspmid35182380 doi101007 s1331102201196w,0.0
incidence bladder cancer neurourological patients france nationwide study world j urol 2022 feb 19 doi 101007 s0034502203955y online ahead printabstractpurpose purpose study evaluate incidence bladder cancer bca patients main neurological diseases induce neurogenic lower urinary tract dysfunction namely multiple sclerosis ms spinal cord injury sci spina bifida sb methods conducted retrospective analysis nationwide data french hospital discharge database pmsi january 2010 december 2018 incidence bca calculated patients ms sci sb incidence sex age radical cystectomy bca diagnosis inhospital deaths compared three groups chi2 kruskalwallis tests used qualitative quantitative data comparisons respectivelyresults overall 2015 neurourological patients mean sd age 654 123 years hospitalized france 2010 2018 new diagnosis bca neurourological patients bca frequent men women sex ratio 308 incidence bca neurourological patients 1749 100 000 persons year incidence bca 7911 100 000 persons year sci compared 566 ms 1138 sb p 00001 initial diagnosis bca 551 273 patients underwent radical cystectomy 613 304 died hospital bca diagnosisconclusions incidence bca france 2010 2018 1749 100 000 persons year particularly high patients scipmid35182207 doi101007 s0034502203955y,0.0
tenyear followup mitoxantrone induction early highly active relapsingremitting multiple sclerosis observational study 100 consecutive patients rev neurol paris 2022 feb 15s00353787 22 000431 doi 101016 jneurol202111014 online ahead printabstractbackground six monthly courses mitoxantrone approved france 2003 patients highly active multiple sclerosis ms objective report 10year clinical followup safety mitoxantrone induction drug followed maintenance therapy patients early highly active relapsingremitting ms rrms expanded disability status scale edss score4 12months prior mitoxantrone initiationmethods total 100 consecutive patients highly active rrms rennes edmus database received monthly mitoxantrone 20mg combined methylprednisolone 1g 3 n75 6months n25 followed firstline diseasemodifying drug dmd 10year clinical impact studied clinical activity dmd exposure adverse eventsresults twentyfour percent relapsefree 10years mean annual number relapses 02 10years mean edss score remained significantly improved 10years changing 35 mitoxantrone initiation 27 10years probability disability worsening improvement mitoxantrone initiation 10years respectively 27 58 13 converted secondary progressive ms patients remained untreated treated firstline maintenance dmd 65years average cohort mitoxantrone generally safe leukemia observed six patients developed neoplasms including 4 solid cancersconclusion monthly mitoxantrone 3 6months followed maintenance firstline treatment may attractive therapeutic option patients early highly active rrms particularly lowincome countriespmid35181157 doi101016 jneurol202111014,0.0
degree cortical plasticity correlates cognitive performance patients multiple sclerosis brain stimul 2022 feb 16s1935861x 22 000353 doi 101016 jbrs202202007 online ahead printabstractbackground cortical reorganization plasticity may compensate structural damage multiple sclerosis ms important establish sensitive methods measure compensatory mechanisms may prognostic valueobjective investigate association degree cortical plasticity cognitive performance compare plasticity ms patients healthy controls hcs methods amplitudes motor evoked potential mep pre post quadripulse stimulation qps applied contralateral motor cortex served measure degree cortical plasticity 63 patients relapsingremitting ms rrms 55 matched hcs main outcomes correlation coefficients difference mep amplitudes post pre qps symbol digit modalities test sdmt brief visuospatial memory testrevised bvmtr qpsxgroup interaction mixed model predicting mep amplituderesults sdmt bvmtr correlated significantly qpsinduced cortical plasticity rrms patients plasticity significantly reduced patients cognitive impairment compared patients preserved cognitive function degree plasticity differentiated patient groups interestingly overall rrms patient cohort show reduced plasticity compared hcsconclusions provide first evidence qpsinduced plasticity may inform global synaptic plasticity rrms correlates cognitive performance well clinical disability larger longitudinal studies patients ms needed investigate relevance prognostic value measure disease progression recoverypmid35182811 doi101016 jbrs202202007,0.0
cellular specificity mitochondrial immunometabolic featuresin major depression mol psychiatry 2022 feb 18 doi 101038 s41380022014732 online ahead printno abstractpmid35181755 doi101038 s41380022014732,0.0
cannabinoid endocannabinoid system promising therapeutic intervention multiple sclerosis mol biol rep 2022 feb 18 doi 101007 s11033022072235 online ahead printabstractmultiple sclerosis ms chronic complex neurodegenerative disease distinguished presence lesions central nervous system cns due exacerbated immunological responses inflict oligodendrocytes myelin sheath axons recent years studies focused targeted therapeutics ms emphasize role g proteincoupled receptors gpcrs specifically cannabinoids receptors clinical studies suggested therapeutic potential cannabinoids derived cannabis sativa relieving pain tremors spasticity cannabinoids also appear prevent exaggerated immune responses cns due compromised bloodbrain barrier endocannabinoid system ecs modulators cannabinoid ligands actively promote oligodendrocyte survival regulating signaling migration myelination nerve cells cannabinoid receptors 1 cb1 2 cb2 ecs main ones focus therapeutic intervention ms various cb1 cb2 receptors agonists experimentally studied showed antiinflammatory properties considered effective potential therapeutics ms review focused exacerbated immune attack nerve cells role cannabinoids interaction ecs cns ms pathologypmid35182322 doi101007 s11033022072235,1.0
tiny size big impact extracellular vesicles modulators mood anxiety neurodevelopmental disorders neurosci biobehav rev 2022 feb 16104582 doi 101016 jneubiorev2022104582 online ahead printabstractextracellular vesicles evs tiny vesicles used cells means cellular communication function state given cell can changed body evidence suggested evs culprits development progression various types diseases including neurodegenerative diseases multiple sclerosis ms alzheimers disease ad unsurprisingly evs also implicate mood anxiety neurodevelopmental disorders major depressive disorder mdd anxiety disorder autismspectrum disorder asd respectively review stateofart regarding roles evs aforementioned diseases focus mechanisms can cause worsen disease harnessing knowledge evs important deliver different cargos cells specific manner treat diseases also establish reliable disease biomarkers will aid early disease diagnosis treatment increasing chance successful treatmentpmid35182538 doi101016 jneubiorev2022104582,0.0
targeting ifn signaling promotes recovery central nervous system autoimmunity j immunol 2022 feb 18ji2101041 doi 104049 jimmunol2101041 online ahead printabstracttype iii ifns ifnls newly discovered cytokines acting epithelial barriers exert immunomodulatory functions addition primary roles antiviral defense study define role ifnls maintaining autoreactive t cell effector function limiting recovery murine model multiple sclerosis ms experimental autoimmune encephalomyelitis genetic abbased neutralization ifnl receptor ifnlr resulted lack disease maintenance experimental autoimmune encephalomyelitis loss cns th1 effector responses limited axonal injury phenotypic effects ifnlr signaling traced increased apc function associated increase t cell production ifn gmcsf consistent ifnl levels within lesions cns tissues derived patients ms elevated compared ms normalappearing white matter furthermore expression ifnlr selectively elevated ms active lesions compared inactive lesions normalappearing white matter findings suggest ifnl signaling potential therapeutic target prevent chronic autoimmune neuroinflammationpmid35181638 doi104049 jimmunol2101041,1.0
prognostic value neurofilament light chain serum lancet neurol 2022 mar 21 3 207208 doi 101016 s14744422 22 000345no abstractpmid35182499 doi101016 s14744422 22 000345,0.0
homebased aerobic training vitamin d improve neurotrophins inflammatory biomarkers ms patients abstractbackgroundlifestyle modifications physical activity diet among promising strategies multiple sclerosis ms rehabilitation study aimed investigate effects combined homebased vit d neurotrophins level biomarker inflammation ms patients covid19 outbreakmethodsin randomized singleblinded placebocontrolled trial 38 females ms edss 35 aged 2040 years body mass index bmi 2530 kg m2 randomly assigned four groups at+vit d n10 n9 vit d n9 control c n10 program consisted 5070 hrmax 2540 min day three days wk eight weeks participants vit d group consumed 50000 iu vit d supplement capsules per week eight weeks data analyzed paired ttest oneway analysis variance tukeynulls post hoc test signification level p005resultsat+vit d vit d compared control increased bdnf ngf downregulated crp tnfa il6 il1 ms patients additionally at+vit d group showed significantly lower crp tnfa il6 il1 levels significantly higher bdnf ngf levels compared vit d groups also results study showed significant differences vit d groups variable mentioned aboveconclusionsthese findings suggest at+vit d improves neurotrophin inflammatory biomarker levels female ms patients effectively vit d alone,0.0
personality styles adherence treatment adult patients multiple sclerosis personality adherence treatment multiple sclerosis abstractsummarythere evidence personality characteristics traits highly prevalent people multiple sclerosis ms objective determine whether personality style adult patients ms associated adherence pharmacological neurorehabilitation treatmentsmethodcrosssection study included 56 adult patients ms adherence drug treatment assessed using measure medication adherence mma scale adherence rehabilitation measured using scale measure adherence neurorehabilitation sman personality styles assessed using millon index personality styles mips inventory analysis primary objective explanatory linear regression model developed adherence variables taken continuous variables independent variables incorporated model one time stepwise analysis adjusting covariates age sex edss level education duration disease treatment comorbidities association independent variable adherence considered significant p less 005resultsthe presence pleasureenhancing painavoiding confident asserting personalities significantly associated increase adherence drug treatment p0012 p0022 p002 respectively presence othernurturing feelingguided dutiful conforming personalities significantly associated lower adherence p0024 p0018 p0029 respectively regard adherence neurorehabilitation women lower adherence compared men pleasureenhancing painavoiding confident asserting personalities p0022 p0016 p0024 respectively also significantly associated increase adherence neurorehabilitation treatment presence othernurturing feelingguided personalities significantly associated lower adherence neurorehabilitation p0024 p0018 respectively conclusionthere personality traits ms patients independently associated adherence pharmacological treatment well neurorehabilitation getting know aspects will enable us develop individualized strategies order foster adherence treatments patients ms,0.0
towards individualized monitoring cognition multiple sclerosis digital era oneyear cohort study abstractbackground cognitive impairment frequent multiple sclerosis ms reliable sensitive individualized monitoring clinical practice still limited smartphoneadapted tests may enhance assessment function tests can performed frequently within daily living environment objectives prove reproducibility smartphonebased symbol digit modalities test ssdmt responsiveness relevant change clinical cognitive outcomes develop individualbased monitoring method cognitionmethods oneyear cohort study 102 patients ms weekly ssdmts performed analyzed reproducibility parameters standard error measurement sem smallest detectable change sdc responsiveness ssdmt relevant change 3monthly clinically assessed sdmt ie 4point change quantified area receiver operating characteristic curve auc curve fitting weekly ssdmt scores individual patients performed local linear trend model estimate visualize denoised cognitive state 95 confidence interval ci optimal assessment frequency determined analyzing ci bandwidth function ssdmt assessment frequencyresults weekly ssdmt showed improved reproducibility estimates sem294 sdc815 compared clinical sdmt aucvalues exceed 070 classifying relevant change csdmt however utilizing weekly ssdmt measurements estimated state curves 95 ci plotted showing detailed changes within individuals time test frequency per 12 days 4point changes ssdmt can detectedconclusion local linear trend model applied ssdmt scores individual patients increases signaltonoise ratio substantially improves detection statistically reliable changes therefore finegrained individualbased monitoring approach can used complement current clinical assessment enhance clinical care mstrial registration netherlands trial register nl7070 https wwwtrialregisternl trial 7070,0.0
imi2paincarebiopainrct1 study protocol randomized doubleblind placebocontrolled crossover multicenter trial healthy subjects investigate effects lacosamide pregabalin tapentadol biomarkers pain processing observed peripheral nerve excitability testing net background new drugs developed chronic pain drug development challenged uncertainty whether drug engages human target sufficiently meaningful pharmacodynamic effect imi2paincarebiopainrct1 one four similarly designed studies aim link different functional biomarkers drug effects nociceptive system serve accelerate future development analgesics study focusses biomarkers derived nerve excitability testing net using threshold tracking peripheral nervous systemmethodsthis multisite singledose subject assessorblind randomized placebocontrolled 4period 4way crossover pharmacodynamic pd pharmacokinetic pk study healthy subjects biomarkers derived net large sensory motor fibers small sensory fibers using perception threshold tracking will obtained three times administration three medications known act nociceptive system lacosamide pregabalin tapentadol placebo given single oral dose least 1 week apart motor sensory net will assessed right wrist nonsensitized normal condition perception threshold tracking will performed bilaterally nonsensitized sensitized forearm skin cutaneous highfrequency electrical stimulation used induce hyperalgesia blood samples will taken pharmacokinetic purposes pain ratings well predictive psychological traits will collected sequentially rejective multiple testing approach will used overall alpha error primary analysis split across two primary outcomes strengthduration time constant sdtc measure passive membrane properties nodal persistent na+ conductance large sensory fibers sdtc large motor fibers comparing lacosamide placebo key secondary endpoint sdtc measured small sensory fibers remaining treatment arm effects key net outcomes pk modelling prespecified secondary exploratory analysesdiscussionmeasurements net using threshold tracking protocols sensitive membrane potential site stimulation sets useful indices axonal excitability collectively may provide insights mechanisms responsible membrane polarization ion channel function activity ionic pumps process impulse conduction imi2paincarebiopainrct1 hypothesizes net can serve biomarkers target engagement analgesic drugs compartment nociceptive system future phase 1 clinical trials phase 2 3 clinical trials also benefit tools patient stratificationtrial registrationthis trial registered 25 06 2019 eudract 201900094236,0.0
sarcopenia motoric cognitive risk syndrome moderated mediation model background sarcopenia identified risk factor cognitive impairment motoric cognitive risk syndrome mcr recently defined predementia syndrome known whether related aimed investigate association potential pathways sarcopenia mcr community elderly establishing moderated mediation modelmethods846 community residents aged 60 years recruited may 2021 september 2021 comprehensive geriatric evaluation diagnosis sarcopenia followed criteria issued asian working group sarcopenia 2019 mcr defined subjective cognitive decline slow gait apathy symptoms physical activity assessed apathy evaluation scale aes international physical activity questionnaire ipaq logistic regression moderated mediation analyses conducted explore association fourresults60 71 mcr among 846 participants full adjustment sarcopenia odds ratio 381 95 confidence interval ci 169860 p 0001 aes score 109 95 ci 104114 p 0001 ipaq level 043 95 ci 028066 p 0001 associated mcr apathy partially mediated relationship sarcopenia mcr physical activity played moderation role indirect pathway mediation model increase physical activity can alleviate indirect effect sarcopenia mcrconclusionwe established moderated mediation model uncover underlying association mechanism sarcopenia mcr preliminarily findings suggest attention paid management apathy physical activity context sarcopenia prevent early dementia actively validation needed future longitudinal studies,0.0
gutoriented interventions patients multiple sclerosis fact fiction eur rev med pharmacol sci 2022 feb 26 3 935946 doi 1026355 eurrev_202202_28003abstractobjective multiple sclerosis ms chronic inflammatory demyelinating disimmune disease central nervous system whose etiology pathogenesis remain poorly understood due complex multifactorial nature evidence bidirectional connection linking gut microbiome intestinal barrier immune system gutbrain axis may implications pathogenesis inflammatory demyelinating diseases ms narrative review summarizes evidence gutbrain axis involvement pathogenesis ms examines role gutoriented interventions mspatients methods reviewed available studies pubmed concerning gutdirected interventions ms research conducted using different combinations pertinent keywords multiple sclerosis immunemediated inflammatory diseases autoimmune diseases first demyelinating event neurocognition neurological disorders neurology practice risk factors taxonomic biomarkers nutrition diet dietary additives complementary treatment gut bacteria gut microbiome microbiome gutbrain axis epidemiology alphalinolenic acid fermentative metabolites fat saturated fat monounsaturated fat polyunsaturated fat omega3 fatty acids calorie restricted diet fasting fecal microbiome fecal microbiota transplantation animal testing results emerging evidence alterations gut microbiome increased intestinal permeability may causative factors complex interplay nutrition metabolic status immuneinflammatory response patients ms suggests possibility modification lifestyle microbiome example specific diets fecal microbiota transplantation supplementation bile acids intestinal barrier enhancers may positively influence pathogenesis msconclusions although role nutritional factors pathogenesis ms remains established evidence appropriate gutdirected interventions diet nutritional supplementation fecal transplantation may modulate inflammatory response improve course ms complementary treatment diseasepmid35179760 doi1026355 eurrev_202202_28003,1.0
treatment rehacom computerized rehabilitation program improves response control attention children attentiondeficit#x2f hyperactivity disorder adhd j clin neurosci 2022 feb 15 98149153 doi 101016 jjocn202202008 online ahead printabstractattentiondeficit hyperactivity disorder adhd common psychiatric disorder children adhd impairs attention response control emotion regulation cognitive functions hand rehacom cognitive rehabilitation software therapeutic effects cognitive dysfunctions many diseases stroke multiple sclerosis schizophrenia goal present study investigate effect treatment rehacom auditory visual response control auditory visual attention children adhd forty patients selected participants assigned control n 20 experimental n 20 groups participants experimental group trained rehacom five weeks ten 45min sessions two sessions per week weeks 0 5 performance participants experimental group compared participants control group results showed treatment rehacom significantly improved auditory visual response control children adhd effect auditory visual attention conclusion rehacom may alter brains structural functional properties related response control suggest attention deficit adhd may result complicated dysfunctions brain affected rehacompmid35180505 doi101016 jjocn202202008,0.0
retinal nerve fiber ganglion cell complex layer thicknesses mirror brain atrophy patients relapsingremitting multiple sclerosis restor neurol neurosci 2022 feb 17 doi 103233 rnn211176 online ahead printabstractbackground multiple sclerosis ms associated progressive brain atrophy turn correlates disability depression cognitive impairment relapsingremitting multiple sclerosis rrms type ms relapses disease followed remission periods common type disease significant need easy lowcost methods cerebral changes changes retinal layer thickness may reflect alterations brain white gray matter volumes therefore paper aims determine whether retinal layer thickness measured using optical coherence tomography oct correlates volumetric brain assessments obtained magnetic resonance imaging mri methods retrospective cohort study recruited 53 patients relapsingremitting ms underwent mri oct examinations evaluation brain compartment volumes thickness retinal layers respectively oct parameters including central retinal thickness retinal nerve fiber layer thickness rnfl peripapillary thickness ganglion cell complex thickness gcc macular thickness expanded disability status scale edss results compared mri parameters cerebral cortex cerebral cortex basal ganglia combined brain hemispheres without ventricular system white matter plaques also checked whether correlation number rrms oct parametersobjective primary objective identify whether patients retinal thickness changes secondary objective check changes correlated mri brain anatomical changesresults rnfl gcc thicknesses strongly pvalue 005 associated cerebral cortex volume ii combination brain cortex basal ganglia volumes iii hemispheres without ventricular system white matter plaques combined showed weak correlation rnfl gcc correlation central retinal thickness brain compartment volumes weak correlations summary edss scores oct resultsconclusions retinal layer thickness measured oct correlates select volumetric brain assessments mri course rrms anatomopathological structure retina might serve surrogate marker brain atrophy clinical progression within selected domainspmid35180139 doi103233 rnn211176,0.0
effectiveness nonpharmacological rehabilitation interventions pain management patients multiple sclerosis systematic review metaanalysis neurorehabilitation 2022 feb 15 doi 103233 nre210328 online ahead printabstractbackground multiple sclerosis ms progressive inflammatory autoimmune neurological disease caused inflammation demyelination central nervous system pain typical symptom central nervous system demyelination affecting 63 adults ms recently role nonpharmacological pain management patients growing nonpharmacological interventions considered safe affordable easy accessible however date systematic reviews metaanalyses comprehensively examined therapeutic effects variety nonpharmacological therapeutic interventions management pain patients msobjective study aimed conduct systematic review metaanalysis assess effectiveness nonpharmacological rehabilitation interventions pain management patients msmethods comprehensive search using pubmed cochrane science direct databases performed included randomized controlled trials randomized crossover trials quasiexperimental trials assessing effect nonpharmacological interventions managing pain patients ms study conducted according prisma guidelines systematic review pairwise metaanalysis metaanalyses performed calculating standardized mean difference 95 confidence interval using review manager softwareresults twentynine papers included systematic review 22 included metaanalysis pooled analysis showed significant effect neuromodulation transcranial direct current stimulation pain intensity reduction patients ms smd 051 95 ci 051 009 p 002 smd 067 95 ci 118 016 p 001 respectively analysis showed significant improvement pain intensity patient ms mindbody therapies smd 045 95 ci 082 07 p 002 mindfulness smd 055 95 ci 096 014 p 0009 hypnosis smd 088 95 ci 130 046 p 00001 trigger point therapies smd 083 95 ci 165 001 p 005 cognitive behavioral therapy smd 064 95 ci 118 011 p 002 however significant effect relaxation therapy pain reduction patients ms smd 082 95 ci 194 031 p 015 conclusions results indicated majority nonpharmacological rehabilitation interventions showed potential therapeutic effects reducing pain intensity patients mspmid35180138 doi103233 nre210328,1.0
assessment smartphonebased spiral tracing multiple sclerosis reveals intraindividual reproducibility major determinant clinical utility digital test front med technol 2022 feb 1 3714682 doi 103389 fmedt2021714682 ecollection 2021abstracttechnological advances lack medical professionals high cost facetoface encounters disasters covid19 pandemic fuel telemedicine revolution numerous smartphone apps developed measure neurological functions however psychometric properties seldom determined unclear designs underlie eventual clinical utility smartphone tests developed smartphone neurological function tests suite neufunts systematically evaluating psychometric properties gold standard complete neurological examination digitalized neurextm app article examines fifth complex neufunts test spiral tracing generated 40 features training cohort 22 healthy donors hd 89 patients multiple sclerosis ms compared intraclass correlation coefficient fold change hd ms correlations relevant clinical imaging outcomes assembled best features machinelearning models examined performance independent validation cohort 45 patients ms show involving multiple neurological functions complex tests spiral tracing susceptible intraindividual variations decreasing reproducibility clinical utility simple tests reproducibly measuring single function s can aggregated increase sensitivity preferable app designpmid35178527 pmcpmc8844508 doi103389 fmedt2021714682,0.0
immune reconstitution following autologous hematopoietic stem cell transplantation multiple sclerosis review behalf ebmt autoimmune diseases working party front immunol 2022 feb 1 12813957 doi 103389 fimmu2021813957 ecollection 2021abstractmultiple sclerosis ms central nervous system cns disorder mediated abnormal immune response coordinated t b cells resulting areas inflammation demyelination axonal loss diseasemodifying treatments dmts available dampen inflammatory aggression ineffective many patients autologous hematopoietic stem cell transplantation hsct used treatment patients highly active disease achieving longterm clinical remission rationale intervention eradicate inflammatory autoreactive cells lymphoablative regimens restore immune tolerance immunological studies demonstrated autologous hsct induces renewal tcr repertoires resurgence immune regulatory cells depletion proinflammatory t cell subsets suggesting resetting immunological memory although understanding clinical immunological effects autologous hsct progressed work required characterize mechanisms underlie treatment efficacy considering memory b cells diseasepromoting stemlike t cells multipotent progenitors involved selfregeneration central effector memory cells investigating reconstitution b cell compartment stem effector subsets immunological memory following autologous hsct elucidate mechanisms since subjects need optimally protected vaccinepreventable diseases including covid19 need ensure vaccination subjects undergoing hsct effective safe additionally study vaccination hscttreated subjects means evaluating immune responses distinguish broad immunosuppression immune resettingpmid35178046 pmcpmc8846289 doi103389 fimmu2021813957,1.0
serum nfl chi3l1 als parkinsonian disorders process diagnosis j neural transm vienna 2022 feb 18 doi 101007 s0070202202470z online ahead printabstractserum neurofilament light chain nfl chitinase 3like 1 chi3l1 also called ykl40 concentrations attractive candidate biomarkers neurodegenerative disorders include amyotrophic lateral sclerosis als parkinsonian disorders aimed assess diagnostic power serum nfl chi3l1 concentrations regard early diagnosis als parkinsons disease pd studied 157 individuals included 41 healthy controls 8 patients als mimics 18 patients initially diagnosed als idals 32 patients latediagnosed als ldals 29 patients pd 12 patients pd mimics 17 patients initially diagnosed atypical parkinsonian disorders idapds initial stage diagnosis electrochemiluminescence used measure concentrations serum nfl chi3l1 diagnostic performance assessed using area receiver operating curves aucs aucs serum nfl 090 discriminating als mimics ldals initial stage diagnosis 089 discriminating als mimics als ld idals aucs serum nfl 076 discriminating pd pd mimics initial stage diagnosis 080 discriminating pd apd significant difference existed serum chi3l1 concentrations individuals suspected als parkinsonism p 014 p 044 respectively serum nfl excellent almost good diagnostic performances patients als pd respectively initial stage diagnosis whereas significant difference existed serum chi3l1 groupspmid35178615 doi101007 s0070202202470z,0.0
ccr6 cxcr6 identify th17 cells cytotoxicity experimental autoimmune encephalomyelitis front immunol 2022 feb 1 13819224 doi 103389 fimmu2022819224 ecollection 2022abstractdue plasticity il17producing cd4 t cells th17 cells longstanding challenge studying th17driven autoimmune lack specific surface marker identify pathogenic th17 cells vivo recently discovered pathogenic cd4 t cells cxcr6 positive experimental autoimmune encephalomyelitis eae commonly used th17driven autoimmune model herein revealed peripheral cxcr6+cd4 t cells contain functionally distinct subpopulation ccr6 positive enriched conventional th17 molecules il23r rort cytotoxic signatures additionally spinal cordinfiltrating cd4 t cells highly cytotoxic expressing granzyme s along ifn gmcsf collectively study suggested peripheral ccr6+cxcr6+cd4 t cells th17 cells cytotoxic property eae model highlighted cytotoxic granzymes eae pathologypmid35178050 pmcpmc8844514 doi103389 fimmu2022819224,0.0
hypnotherapy nonpharmacological treatment psychological symptoms multiple sclerosis altern ther health med 2022 feb 18at7070 online ahead printabstractcontext stress chronic pain factors influence quality life wellbeing people ms 90 adults ms suffer persistent fatigue symptoms can associated disorders depression drug treatments provide inadequate comfort people themobjective study intended examine impact hypnosis hypnotherapy management symptoms people multiple sclerosis ms stress chronic pain inferior quality life lack psychological wellbeingdesign research team performed systematic narrative review searching pubmed web science databases including review articles studies additional citationssetting study conducted scientific institute research irccs messinaresults 14 121 publications met inclusion criteria selected hypnotic treatment effective therapy beneficial impacts intensity perceived pain psychological wellbeing mood disorders fatigue addition significantly improves physical functioning ms patients effects havent obtained nonpharmacological techniquesconclusion hypnosis appropriate psychological therapy management ms patients symptomspmid35180100,0.0
choroid plexusselective inactivation adenosine a2a receptors protects t cell infiltration experimental autoimmune encephalomyelitis background multiple sclerosis ms one common autoimmune disorders characterized infiltration immune cells brain demyelination unwanted immunosuppressive side effect therapeutically successful natalizumab led us focus choroid plexus cp key site first wave immune cell infiltration experimental autoimmune encephalomyelitis eae control immune cells trafficking adenosine a2a receptor a2ar emerging potential pharmacological target control eae pathogenesis however cellular basis a2armediated protection remains undeterminedmethodsin eae model assessed a2ar expression leukocyte trafficking determinants cp immunohistochemistry qpcr analyses determined effect a2ar antagonist kw6002 treatment days 812 814 postimmunization t cell infiltration across cp eae pathology determined critical role cpa2ar t cell infiltration eae pathology focal knockdown cpa2ar via intracerebroventricular injection cretat recombinase a2arflox flox mice cultured cp epithelium also evaluated effect overexpression a2ars a2ar agonist cgs21680 treatment cp permeability lymphocytes migrationresultswe found specific upregulation a2ar cp associated enhanced cp gateway activity peaked day 12 postimmunization eae mice furthermore kw6002 treatment days 812 814 postimmunization reduced t cell trafficking across cp attenuated eae pathology importantly focal cpa2ar knockdown attenuated pathogenic infiltration th17+ cells across cp via inhibiting ccr6ccl20 axis nfb stat3 pathway protected eae pathology lastly activation a2ar cultured epithelium a2ar overexpression cgs21680 treatment increased permeability cp epithelium facilitated lymphocytes migrationconclusionthese findings define cp niche one primary sites a2ar action whereby a2ar antagonists confer protection eae pathology thus pharmacological targeting cpa2ar represents novel therapeutic strategy ms controlling immune cell trafficking across cp,1.0
insight mitochondrial unfolded protein response cancer opportunities challenges abstractthe mitochondrial unfolded protein response uprmt evolutionarily conserved protective transcriptional response maintains mitochondrial proteostasis inducing expression mitochondrial chaperones proteases response various stresses uprmtmediated transcriptional program requires participation various upstream signaling pathways molecules factors regulating uprmt caenorhabditis elegans c elegans mammals similar different cancer cells malignant cells uncontrolled proliferation exposed various challenges endogenous exogenous stresses therefore cancer cells uprmt hijacked exploited repair mitochondria promotion tumor growth invasion metastasis review systematically introduce inducers uprmt biological processes uprmt participates mechanisms regulating uprmt c elegans mammals crosstissue signal transduction uprmt roles uprmt promoting cancer initiation progression disrupting proteostasis cancer cells targeting uprmt constitutes novel anticancer therapeutic strategy,0.0
relationship white matter lesions gray matter atrophy multiple sclerosis systematic review neurology 2022 feb 16101212 wnl0000000000200006 doi 101212 wnl0000000000200006 online ahead printabstractbackground currently consensus extent gray matter gm atrophy can attributed secondary changes following white matter wm lesions temporal spatial relationships two phenomena elucidating interplay will broaden understanding combined inflammatory neurodegenerative pathophysiology multiple sclerosis ms separating atrophic changes due primary secondary neurodegenerative mechanisms will pivotal properly evaluate treatment effects especially treatments target different processes individuallyobjective untangle complex pathological mechanisms systematic review provides essential first step objective comprehensive overview existing vivo knowledge relationship brain wm lesions gm atrophy patients diagnosed ms overall aim clarify extent wm lesions associate global regional gm atrophy may differ different disease subtypesmethods searched medline pubmed embase reports containing direct associations brain gm wm lesion measures obtained conventional mri sequences patients clinically isolated syndrome cis ms restriction applied publication date quality risk bias included studies evaluated using quality assessment tool observational cohort crosssectional studies nih bethesda ma qualitative descriptive analyses performedresults total 90 articles included wm lesion volumes mostly related global cortical deep gm volumes significant associations almost without exception negative indicating higher wm lesion volumes associated lower gm volumes lower cortical thicknesses consistent relation wm lesions gm atrophy seen early relapsing disease less progressive msconclusion findings suggest gm neurodegeneration mostly secondary damage wm early disease stages becoming detached dominated possibly primary neurodegenerative disease mechanisms progressive mspmid35173016 doi101212 wnl0000000000200006,0.0
improving awareness transform outcomes degenerative cervical myelopathy ao spine recodedcm research priority number 1 global spine j 2022 feb 12 1_suppl 28s38s doi 101177 21925682211050927abstractstudy design literature review narrative objective introduce number one research priority degenerative cervical myelopathy dcm raising awarenessmethods raising awareness recognized ao spine recodedcm number one research priority article reviews evidence awareness low potential drivers must addressed case studies success diseases also reviewed drawing potential parallels opportunities dcmresults dcm may affect many 1 50 adults yet will receive diagnosis will wait many years leads poorer outcomes surgery greater disability dcm rarely featured healthcare professional training programs received relatively little research funding 2 amyotrophic lateral sclerosis multiple sclerosis last 25 years transformation stroke acute coronary syndrome services position best supportive care occasional surgery 50 years ago avoidable disability today represents transferable examples success potential opportunities dcm central raising awarenessconclusion despite devastating burden patient recognition across research clinical practice healthcare policy limited dcm represents significant unmet need must become international public health prioritypmid35174734 doi101177 21925682211050927,0.0
artificial double inversion recovery images can substitute conventionally acquired images mrihistology study sci rep 2022 feb 16 12 1 2620 doi 101038 s41598022065464abstractcortical multiple sclerosis lesions diseasespecific yet inconspicuous magnetic resonance images mri double inversion recovery dir images sensitive often unavailable clinical routine clinical trials artificially generated images can mitigate issue lack histopathological validation work artificial dir images generated postmortem 3dt1 protondensity pd t2 3dt1 3d fluidinversion recovery flair images using generative adversarial network sequences scored cortical lesions blinded histopathology subsequently tissue samples stained proteolipid protein myelin scored cortical lesions type iiv leukocortical intracortical subpial cortexspanning respectively histopathological scorings unblinded compared mri using linear mixed models images 38 patients 26 female mean age 643 107 included total 142 cortical lesions detected predominantly subpial histopathologyblinded unblinded sensitivity 134 352 artificial dir generated t1pd t2 141 415 artificial dir t1flair 176 493 conventional dir 106 345 3dt1 blinded histopathology differences histopathological feedback hand conventional dir artificial dir t1flair outperformed sequences differences histopathologyblinded unblinded sensitivity minified adjustment scoring criteria conclusion artificial dir images particularly generated t1flair potentially substitute conventional dir images unavailablepmid35173226 doi101038 s41598022065464,1.0
efficacy safety sampeginterferon beta1a treatment relapsing remitting multiple sclerosis results 52 weeks therapy randomized doubleblind clinical trial zh nevrol psikhiatr im s s korsakova 2022 122 1 6271 doi 1017116 jnevro202212201162abstractobjective evaluate efficacy safety sampegifn1a 180 g 240 g administered every 2 weeks treatment relapsing remitting multiple sclerosis rrms compared placebo low dose interferon beta1a lib 30 g administered weekly primary endpoint 52 weeks therapy time first relapse hypotheses noninferiority superiority lib testedmaterial methods international multicenter double blind comparative placebocontrolled clinical study enrolled 399 patients diagnosis rrms randomized 4 groups sampegifn1a180 g n114 sampegifn1a 240 g n114 lib n114 placebo n57 placebo group patients participated study 20 weeks 52 weeks therapy 4 weeks followup lib group patients completed participation study patients pegifn1a groups continued receive therapy week 100 inclusive article presents results analysis conducted end 52 weeks doubleblind comparative randomized placebocontrolled clinical trialresults final analysis efficacy safety performed 52 weeks study main statistical hypothesis testing proved doses sampegifn1a equally effective compared lib primary endpoint time first relapse due detection statistically significant differences primary endpoint study drug reference drug indicating greater efficacy study drug additional testing carried hypothesis superiority sampegifn1a dose 240 g reference lib proved evaluation dynamics certain key parameters magnetic resonance imaging mri brain clinical outcomes demonstrated positive effect sampegifn1a therapy form decreased activity demyelinating process brain reduce number relapses proportion patients without new t2 lesions 52 weeks 876 904 180 g 240 g sampegifn1a groups versus 726 lib group p00199 p00033 progression multiple sclerosis shown based edss scale evaluation study common adverse reactions flulike symptoms injection site reactionsconclusion new drug sampegifn1a effective safe agent relapsing remitting multiple sclerosis treatment advantage lowdose interferons form reduced frequency intramuscular injectionspmid35175704 doi1017116 jnevro202212201162,1.0
forgotten tract vision multiple sclerosis vertical occipital fasciculus fiber properties visuospatial memory brain struct funct 2022 feb 17 doi 101007 s00429022024643 online ahead printabstractvisual disturbances common disease manifestation multiple sclerosis ms due lesions damaging white matter tracts involved vision vertical occipital fasciculus vof tract located vertically occipital lobe neglected century hypothesize vof involved integrating information dorsal ventral visual streams thus damage ms well probable role visual processing using ms vof damage model needs clarified study fiber characteristics vof ms clinical visual learning associations 57 relapsingremitting ms rrms 25 healthy controls hc recruited acquired ms functional composite expanded disability status scale edss brief visuospatial memory testrevised bvmtr diffusion mri scans tractography vof optic radiation done vofs metrics statistically tested betweengroup differences clinical visual tests associations alongtract analysis laterality also tested rrms patients higher mean axial radial diffusivity nearly fiber points lower fractional anisotropy bilateral vofs compared hc laterality noted associated poor clinical outcomes poor visual scores edss lower total immediate delayed recall bvmtr rrms adjusting age gender fiber metrics vof damage present rrms associated visual symptoms visuospatial learning impairments seems vof involved integrating information visual streamspmid35174417 doi101007 s00429022024643,0.0
subcutaneous cladribine treat multiple sclerosis experience 208 patients ther adv neurol disord 2021 nov 25 1417562864211057661 doi 101177 17562864211057661 ecollection 2021abstractobjective report safety effectiveness subcutaneous cladribine litak multiple sclerosis ms patientsmethods litak offered mspatients irrespective disease course litak 10 mg administered 34 days week 1 based lymphocyte count week 4 patients received another 03 doses week 5 second course administered 11 months later followup included adverse events relapses expanded disability status scale edss 9holepeg timed25footwalking tests noevidenceofdiseaseactivity neda noevidenceofprogressionoractivedisease nepad mri cerebrospinal fluid csf neurofilament light chain nfl lymphocyte countsresults 208 patients received least one course treatment age baseline 44 1772 years edss 085 cladribine generally well tolerated one myocardial infarction one breast cancer three severe skin reactions occurred without longterm sequelae two patients died one pneumonia one encephalitis lymphopenia grade 3 occurred 5 grade 4 05 94 116 pwms baseline followup bafu data two treatment courses edss remained stable improved 18 months 64 patients relapsing ms bafu data n 39 neda 19 months 62 patients progressive ms bafu data n 13 nepad n 13 patients whose csfnfl baseline elevated 77 normalised within 12 monthsconclusions litak well tolerated effectiveness relapsing ms appeared similar cladribine tablets encouraging progressive ms data suggest cladribine may safe effective mspatients irrespective disease stagepmid35173808 pmcpmc8842147 doi101177 17562864211057661,0.0
recent advancements nanoparticlemediated approaches restoration multiple sclerosis j control release 2022 feb 14s01683659 22 000839 doi 101016 jjconrel202202009 online ahead printabstractmultiple sclerosis ms autoimmune disease complicated immunopathology necessitates considering multifactorial aspects management nanosized pharmaceutical carriers named nanoparticles nps can support impressive management disease early detection prognosis level also therapeutic manner prominent initiator ms domination cellular immunity humoral immunity increment inflammatory cytokines administration several platforms nps ms management holds great promise far efforts ms management vitro vivo experimental animal models evaluations pave new way highly efficient therapeutic means aiding translation clinic near futurepmid35176392 doi101016 jjconrel202202009,1.0
stem cell therapy covid19 pneumonia mol biomed 2022 feb 17 3 1 6 doi 101186 s43556021000678abstractsevere acute respiratory syndrome coronavirus 2 sarscov2 virus highly contagious microorganism despite substantial investigation progress achieved treating postcovid complications however virus made various mutations spread around world researchers tried different treatments reduce side effects covid19 symptoms one common effective treatments now used steroid therapy reduce complications disease longterm steroid therapy chronic inflammation following covid19 harmful increases risk secondary infection effective treatment remains challenging owing fibrosis severe inflammation infection sometimes immune system can severely damage ourselves disease past many researchers conducted various studies immunomodulatory properties stem cells property stem cells led modulate immune system autoimmune diseases like diabetes multiple sclerosis parkinsons immunomodulatory properties stem cellbased therapy employing mesenchymal hematopoietic stem cells may viable alternative treatment option patients priming immune system providing cytokines chemokines growth factors stem cells can employed build longterm regenerative protective response review addresses latest trends rapid progress stem cell treatment acute respiratory distress syndrome ards following covid19pmid35174448 doi101186 s43556021000678,0.0
relationship adaptation disease selfcare agency levels patients multiple sclerosis j neurosci nurs 2022 feb 16 doi 101097 jnn0000000000000630 online ahead printabstractbackground multiple sclerosis ms inflammatory demyelinating disorder central nervous system patients ms difficulties physical social psychological functions study carried determine relationship adaptation levels patients ms disease selfcare agency levels methods study used descriptive design carried university hospitals neurology clinic outpatient clinic july 2019 march 2020 sample size determined 258 using known universe sampling method data collected using adaptation chronic illness scale selfcare agency scale patient identification form spearmen correlation analysis used evaluate data results mean age patients participating study 4136 074 years 74 ms 3 years 58 last attack year ago 27 balance problems adaptation levels patients disease 7679 057 selfcare agency 8842 134 slightly higher moderate level moderatelevel significant positive correlation found adaptation level patients chronic illness selfcare agency levels r 0310 p 000 conclusion concluded moderatelevel significant positive correlation patients level adaptation ms disease level selfcare agency recommend provision supportive professional training patients ms diseasepmid35175988 doi101097 jnn0000000000000630,1.0
mental practice manipulative skills training among people multiple sclerosis pilot study j occup ther 2022 mar 1 76 2 7602205040 doi 105014 ajot2022044479abstractimportance multiple sclerosis ms demyelinating disease central nervous system produces motor cognitive dysfunctions impairments limb function result ms cause decline performance activities daily living adls objective determine whether use mental practice mp mp combined training motor manipulation skills skills training improve gross fine motor skills treatment satisfaction among people msdesign pilot study duration 3 mo plus 3mo followupsetting two ms associationsparticipants thirtyfive patients diagnosed ms relapsingremitting progressive secondary subtypes ages 25 60 yrintervention participants allocated one three groups according order inclusion study 1 mp 2 mp + skills training 3 control group treatment protocol 6wk duration total 12 sessions outcomes measures blinded evaluators performed three assessments patient pretreatment posttreatment 3mo followup using ninehole peg test box block test abilhand canadian occupational performance measure copm results found evidence benefits selfperceived performance adls respect gross fine motor skills however improvement perceived satisfaction performance activities independent treatment receivedconclusions relevance perceived adl performance satisfaction performance increases among people ms receive mp mp + skills training conventional rehabilitation treatment article adds mental practice combined conventional treatment contribute patients perceiving improved performance adls selfreported outcome measures copm provide highly valuable information occupation performance may match objective evidencepmid35175336 doi105014 ajot2022044479,1.0
multiple sclerosis prodrome evidence action front neurol 2022 jan 31 12761408 doi 103389 fneur2021761408 ecollection 2021abstracta growing body work points toward existence clinically symptomatic prodromal phase multiple sclerosis ms might span 510 years prodrome early set signs symptoms predating onset classical disease turn predates definitive diagnosis evidence prodromal phase ms major implications prevention earlier recognition treatment well improved disease course prognosis perspective provides succinct overview recent advances understanding ms prodrome current key challenges many ms prodromal features characterized thus far nonspecific common general population single feature alone sufficient identify individual prodromal ms biomarkers may increase specificity accuracy detecting individuals ms prodromal phase yet discovered formally validated progress made elucidation prodromal phases neurological immunemediated diseases suggests barriers can overcome therefore knowledge prodromal phase ms remains nascent best move rapidly growing evidence researchrelated action critical immediate implications include refining concept ms continuum include prodromal phase will help inform true risk period considering exposures might cause ms major longterm implications include earlier recognition ms improved prognosis earlier disease management future possibility ms disease preventionpmid35173664 pmcpmc8841819 doi103389 fneur2021761408,0.0
effect homebased virtual reality training telerehabilitation balance individuals parkinson disease multiple sclerosis stroke systematic review metaanalysis neurol sci 2022 feb 17 doi 101007 s10072021058552 online ahead printabstractobjective last decade growing interest use virtual reality rehabilitation clinical home settings aim systematic review summary current evidence effect homebased virtual reality training telerehabilitation postural balance individuals central neurological disordersmethods literature searched pubmed web science pedro sciencedirect medline randomized controlled trials rcts evaluating effect homebased virtual reality vr training telerehabilitation tr postural balance patients parkinsons disease multiple sclerosis stroke studies imported endnote excel perform two screening phases four reviewers risk bias assessed using pedro scale cochrane assessment tool risk bias synthesis data comparative outcomes performed using revman softwareresults seven rcts included three pathologies represented vr tr consisted training device eg nintendo wii xbox 360 monitoring device eg skype microsoft kinect five studies used berg balance scale bbs measuring postural balance across studies improvement bbs scores time experimental control groups effect remained followup groups however significant difference groups postintervention md 074 p 045 conclusion homebased vr tr can used prolongation conventional therapypmid35175439 doi101007 s10072021058552,0.0
caudovirales bacteriophages associated improved executive function memory flies mice humans cell host microbe 2022 feb 11s19313128 22 00049x doi 101016 jchom202201013 online ahead printabstractgrowing evidence implicates gut microbiome cognition viruses abundant life entities planet commonly overlooked component gut virome dominated caudovirales microviridae bacteriophages show discovery n 114 validation cohort n 942 subjects increased caudovirales siphoviridae levels gut microbiome better performance executive processes verbal memory conversely increased microviridae levels linked greater impairment executive abilities microbiota transplantation human donors increased specific caudovirales 90 siphoviridae family levels led increased scores novel object recognition test mice upregulated memorypromoting immediate early genes prefrontal cortex supplementation drosophila diet 936 group lactococcal siphoviridae bacteriophages resulted increased memory scores upregulation memoryinvolved brain genes thus bacteriophages warrant consideration novel actors microbiomebrain axispmid35176247 doi101016 jchom202201013,0.0
advanced diffusion mr imaging multiple sclerosis brain spinal cord magn reson med sci 2022 feb 15 doi 102463 mrmsrev20210091 online ahead printabstractdiffusion tensor imaging dti established usefulness evaluating normalappearing white matter nawm lesions difficult evaluate routine clinical mri evaluation brain spinal cord lesions multiple sclerosis ms demyelinating disease recent advances software hardware mri systems increasingly complex sophisticated mri analysis methods qspace imaging diffusional kurtosis imaging neurite orientation dispersion density imaging white matter tract integrity multiple diffusion encoding referred advanced diffusion mri proposed capable capturing vivo microstructural changes brain spinal cord normal pathological states greater detail dtithis paper reviews current status recent advanced diffusion mri assessing ms vivo part issue celebrating two decades magnetic resonance medical sciences mrms official journal japanese society magnetic resonance medicinepmid35173096 doi102463 mrmsrev20210091,1.0
function therapeutic value astrocytes neurological diseases nat rev drug discov 2022 feb 16 doi 101038 s4157302200390x online ahead printabstractastrocytes abundant glial cells central nervous system cns perform diverse functions health disease astrocyte dysfunction found numerous diseases including multiple sclerosis alzheimer disease parkinson disease huntington disease neuropsychiatric disorders astrocytes regulate glutamate ion homeostasis cholesterol sphingolipid metabolism respond environmental factors implicated neurological diseases astrocytes also exhibit significant heterogeneity driven developmental programmes stimulusspecific cellular responses controlled cns location cellcell interactions mechanisms review highlight general mechanisms astrocyte regulation potential therapeutic targets including drugs alter astrocyte metabolism therapies target transporters receptors astrocytes emerging ideas engineered probiotics gliatoneuron conversion therapies also discussed propose concise nomenclature astrocyte subsets use highlight roles astrocytes specific subsets neurological diseasespmid35173313 doi101038 s4157302200390x,0.0
brain antigens stimulate proliferation t lymphocytes pathogenic phenotype multiple sclerosis patients front immunol 2022 jan 31 13835763 doi 103389 fimmu2022835763 ecollection 2022abstracta method stimulate t lymphocytes broad range brain antigens facilitate identification autoantigens multiple sclerosis enable definition pathogenic mechanisms important multiple sclerosis previous work found obvious approach culturing leukocytes homogenized brain tissue work brain homogenate suppresses antigenspecific lymphocyte proliferation now report method substantially reduces suppressive activity used nonsuppressive brain homogenate stimulate leukocytes multiple sclerosis patients controls also stimulated common viruses comparison measured proliferation selected responding cd3+ cells flow cytometry sequenced transcriptomes mrna tcell receptor sequences mrna expression suggested brainresponding cells ms patients potentially pathogenic tcell receptor repertoire brainresponding cells clonal minimal overlap virus antigenspmid35173742 pmcpmc8841344 doi103389 fimmu2022835763,0.0
intensive circuit class therapy patients relapsingremitting multiple sclerosis j rehabil med 2022 feb 17 doi 102340 jrmv542027 online ahead printabstract longterm physiotherapy considerable benefit patients motor dysfunction gait impairment patients multiple sclerosis ms aim study determine effectiveness 12week intensive circuit class therapy ict patients ms wider focus fatigue gait ability methods total 46 relapsingremitting ms patients divided randomly twentythree mean expanded disability status scale edss 233074 took part intensive 12week course ict 23 mean edss 204063 served control group edss timed go tug test fourstage balance test fsbt made physical testing part supplemented questionnaires modified fatigue impact scale mfis 12item multiple sclerosis walking scale msws12 beck depression inventory bdi 36item short form survey sf36 results significant improvements found among ictexercising patients fsbt p005 tug test p001 mfis p001 bdi p005 msws12 p005 three subscales sf36 12 weeks ict significant changes control group ictexercising patients exhibited significant improvements fsbt p0005 tug test p0005 mfis p0001 bdi p0002 msws12 p0001 three subscales sf36 12 weeks ict compared control group conclusion intensive circuit class therapy effective therapeutic approach improving gait balance problems patients ms also proved alleviate fatigue symptoms depressionpmid35174869 doi102340 jrmv542027,1.0
gut microbiota composition related ad pathology front immunol 2022 jan 31 12794519 doi 103389 fimmu2021794519 ecollection 2021abstractintroduction several studies reported alterations gut microbiota composition alzheimers disease ad patients however observed differences consistent across studies aimed investigate associations gut microbiota composition ad biomarkers using machine learning models patients ad dementia mild cognitive impairment mci subjective cognitive decline scd materials methods included 170 patients amsterdam dementia cohort comprising 33 ad dementia 66 8 years 46f minimental state examination mmse 21 1924 21 mci 64 8 years 43f mmse 27 2529 116 scd 62 8 years 44f mmse 29 2830 fecal samples collected gut microbiome composition determined using 16s rrna sequencing biomarkers ad included cerebrospinal fluid csf amyloidbeta 142 amyloid phosphorylated tau ptau mri visual scores medial temporal atrophy global cortical atrophy white matter hyperintensities associations gut microbiota composition dichotomized ad biomarkers assessed machine learning classification models two models highest area curve auc selected logistic regression assess associations 20 best predicting microbes outcome measures machine learning models adjusting age sex bmi diabetes medication use mmseresults machine learning prediction amyloid ptau microbiota composition performed best aucs 064 063 highest ranked microbes included several short chain fatty acid scfa producing species higher abundance clostridium leptum lower abundance eubacterium ventriosum group spp lachnospiraceae spp marvinbryantia spp monoglobus spp ruminococcus torques group spp roseburia hominis christensenellaceae r7 spp associated higher odds amyloid positivity found associations lower abundance lachnospiraceae spp lachnoclostridium spp roseburia hominis bilophila wadsworthia higher odds positive ptau statusconclusions gut microbiota composition associated amyloid ptau status extend recent studies observed associations scfa levels ad csf biomarkers showing lower abundances scfaproducing microbes associated higher odds positive amyloid ptau statuspmid35173707 pmcpmc8843078 doi103389 fimmu2021794519,0.0
women#39 s health multiple sclerosis scoping review front neurol 2022 jan 31 12812147 doi 103389 fneur2021812147 ecollection 2021abstractbackground women multiple sclerosis ms may face challenges related managing reproduction pregnancy menopause simultaneously managing disease purpose scoping review map literature broadly related topics relevant womens health ms inform clinical research communities existing types sources evidence knowledge gaps apart coverage topics within field womens health interested potential gaps related geographic racial ethnic diversity also aimed understand degree inclusion women progressive ms researchmethods searched embase ovid medline databases 1980 november 23 2020 included casecontrol cohort studies clinical trials case series published language conducted women ms clinically isolated syndrome radiologically isolated syndrome addressed womens health two reviewers independently screened abstracts fulltext reports study inclusion completed data extractionresults 112 106 citations screened 1 041 underwent fulltext review 353 met inclusion criteria number studies regarding womens health increased exponentially time almost half studies conducted least part europe 217 conducted north america one study conducted africa studies report race ethnicity participants n 308 872 among 353 studies 509 topics reported studies addressed one topic onethird focused pregnancy n 201 372 followed fetal neonatal outcomes 144 sexual dysfunction 10 among 201 studies focused pregnancy 51 254 included participants progressive msconclusions review identifies important knowledge gaps related womens health ms particularly need future studies include participants broader range races ethnicities progressive ms living asiapacific african regionspmid35173669 pmcpmc8841798 doi103389 fneur2021812147,0.0
twin study reveals nonheritable immune perturbations multiple sclerosis nature 2022 feb 16 doi 101038 s41586022044194 online ahead printabstractmultiple sclerosis ms chronic inflammatory disorder central nervous system underpinned partially understood genetic risk factors environmental triggers undefined interactions1 2 investigated peripheral immune signatures 61 monozygotic twin pairs discordant ms dissect influence genetic predisposition environmental factors using complementary multimodal highthroughput highdimensional singlecell technologies conjunction datadriven computational tools identified inflammatory shift monocyte cluster twins ms coupled emergence population il2 hyperresponsive transitional naive helper t cells msrelated immune alterations integrating data immune profiles healthy monozygotic dizygotic twin pairs estimated variance cd25 expression helper t cells displaying naive phenotype largely driven genetic shared early environmental influences nonetheless expanding helper t cells twins ms also elevated nontwin patients ms emerged independent individual genetic makeup cells expressed central nervous systemhoming receptors exhibited dysregulated cd25il2 axis proliferative capacity positively correlated ms severity together matchedpair analysis extended twin approach allowed us discern genetically environmentally determined features msassociated immune signaturepmid35173329 doi101038 s41586022044194,0.0
potentials barriers using digital tools collecting daily measurements multiple sclerosis research digit health 2021 nov 26 720552076211055552 doi 101177 20552076211055552 ecollection 2021 jandecabstractobjective digital tools offer new ways collecting outcome data intervention research little known potentials barriers using tools outcome measurement multiple sclerosis trials study aimed examine reporting adherence barriers experienced people multiple sclerosis intervention study using three different digital tools outcome measurementmethods mixedmethods study conducted context randomized controlled trial data collected randomized controlled trial analysed assess reporting adherence twentythree semistructured indepth interviews conducted investigate randomized controlled trial participants experiencesresults reporting adherence high three measurement tools lower control group four main barriers defined 1 selfmonitoring aspect repeated tests imbedded digital tools affected participants behavior randomized controlled trial 2 selfmonitoring caused participants worry health 3 passively collected data always correspond participants experiences caused question validity collected data 4 daily reporting using different digital tools placed significant burden participantsconclusion study indicates high reporting adherence using digital tools among people multiple sclerosis however future studies carefully consider overall burden imposed participants taking approach measures taken avoid potential unintended effects selfmonitoring gamification aspects using digital tools measures include passive monitoring reducing frequency reporting blinding participants datapmid35173979 pmcpmc8842387 doi101177 20552076211055552,0.0
multiact model path forward participatory anticipatory governance health research care abstractthe covid19 pandemic unmasked even clearly need research care form unique interdependent ecosystem concept emerged recent years fact address urgent unexpected missions fighting together covid19 pandemic importance multistakeholder collaboration missionoriented governance flexibility demonstrated great efficacy calls policy integration strategy implementation responsible research innovation principles health promoting effective cooperation science society towards shared mission article describes multiact framework discusses innovative approach encompassing governance criteria patient engagement multidisciplinary impact assessment represents holistic management model structuring responsible research innovation participatory governance brain conditions research,0.0
genderaffirming hormone therapy induces specific dna methylation changes blood background dna methylation epigenetic mark influenced underlying genetic profile environment ageing addition xlinked dna methylation sexspecific methylation patterns widespread across autosomal chromosomes can present birth arise time individuals gender identity sex assigned birth markedly incongruent case transgender people feminization masculinization may sought genderaffirming hormone therapy gaht gaht cornerstone transgender care yet studies date investigated effect genomewide methylation profiled genomewide dna methylation blood transgender women n 13 transgender men n 13 gaht 6 months 12 months feminizing masculinizing hormone therapy resultswe identified several thousand differentially methylated cpg sites dmps 002 unadjusted p value 005 several differentially methylated regions dmrs people undergoing feminizing masculinizing gaht vast majority progressive changes time x chromosome sexspecific autosomal dna methylation patterns established early development largely refractory change association gaht 3 affected 002 unadjusted p value 005 small number sexspecific dmps affected gaht become sexspecific lifetime known sexandage dmps including dmrs prr4 vmp1 genes gahtinduced changes sexassociated probes consistently demonstrated shift towards methylation signature gahtnave opposite sex observed enrichment previously reported adolescenceassociated methylation changesconclusionwe provide evidence gaht inducing unique blood methylation signature transgender people study advances understanding complex interplay sex hormones sex chromosomes dna methylation context immunity highlight need broaden field sexspecific immunity beyond cisgender males cisgender females transgender people gaht exhibit unique molecular profile,0.0
attenuation osteoarthritis progression intraarticular injection combination synovial membranederived mscs smmscs plateletrich plasma prp conditioned medium secretome abstractpurposeosteoarthritis oa progressive destructive disease articular cartilage common joint disease characterized reduction joint cartilage thickness demolition cartilage surface new bone formation overcome problems purpose current research evaluate compare vivo effects synovial membranederived mesenchymal stem cell smmscs plateletrich plasma prp conditioned medium secretome collagenase iiinduced rat knee osteoarthritis koa remedymethodsfor first step smmscs isolated characterized also secretome collected smmscs culture furthermore prp collect rat heart venous blood second two injection collagenase ii interval 3 days performed knee intraarticular space induce osteoarthritis two weeks later animals randomly divided 6 groups control group without treatment positive group taken intraarticular sodium hyaluronate injection 01 ml treatment groups taken intraarticular injection treatment 1 smmscs 5 106 treatment 2 smmscs 5 106 secretome 50 l treatment 3 smmscs 5 106 prp 50 l treatment 4 smmscs 5 106 secretome 50 l prp 50 l three months later rats killed following assessments executed radiography histopathology immunohistochemistryresultsour findings represented combination smmscs secretome prp considerable effect glycosaminoglycans gags collagen ii contents articular cartilage preservation compared groups addition combination smmscs prp secretome showed lowest expression mmp3 sox9 highest expression comparison groups also smmscsinjected groups demonstrated better results compared positive control groupsconclusionsinjecting combination smmscs secretome prp resulted better efficacy terms joint space width articular cartilage surface continuity integrity subchondral bone ecm constituents collagen ii indeed transplantation combination considered preliminary therapy clinical trial study future,0.0
sixmonth humoral response bnt162b2 mrna covid19 vaccine people multiple sclerosis treated natalizumab neurol sci 2022 feb 16 doi 101007 s10072022059400 online ahead printabstractbackground studies investigated immune response sarscov2 vaccine patients multiple sclerosis pwms treated natalizumab ntz found shortterm efficient humoral response however studies assessing levels sarscov2 igg antibodies pwms treated ntz timemethods humoral immune response bnt162b2 mrna covid19 vaccine assessed group 26 pwms ntz 6 months full covid19 vaccination cycle compared 43 age sexmatched group hc serum samples collected first dose t0 4 weeks t1 6 months t2 first dose bnt162b2 mrna covid19 vaccine liaison sarscov2 trimericsigg assay diasorinspa employed detection igg antibodies sarscov2 spike protein cutoff positive igg antibodies 338 bau ml results t1 t2 groups showed efficient humoral response bnt162b2 mrna covid19 vaccine significant reduction igg antibodies sarscov2 spike protein detected t2 pwms hc sarscov2 igg antibodies still cutoff limit participantsconclusions pwms ntz develop maintain longterm humoral response full covid19 vaccination cycle comparable healthy peers findings relevant clinicians called counsel covid19 mrna vaccine timing booster doses pwms treated ntzpmid35171373 doi101007 s10072022059400,0.0
protocols measuring stability cytotoxicity cyclotides methods enzymol 2022 6631940 doi 101016 bsmie202109007 epub 2021 nov 9abstractcyclotides plant hostdefense peptides wide range biological activities diverse potential applications medicine agriculture 2737 amino acid peptides headtotail cyclic backbone built around cystine knot core makes exceptionally stable stability amenability sequence modifications made cyclotides attractive scaffolds drug design many synthetic cyclotides now designed synthesized test efficacy leads wide range diseases including infectious disease cancer pain multiple sclerosis additionally natural cyclotides selectively toxic certain cancer cell lines opening potential anticancer agents others insecticidal activity applications crop protection applications mind need able measure cyclotides pharmaceutical agrichemical formulations biological media blood serum well assess potential persistence environment used agrichemical agents chapter describes protocols quantifying cyclotides biological fluids measuring stability assessing relative cytotoxicity various types cellspmid35168789 doi101016 bsmie202109007,0.0
initial experience magnetic resonanceguided focused ultrasound stereotactic surgery central brain lesions young adults j neurosurg 2022 jan 1418 doi 103171 202110jns21416 online ahead printabstractobjective magnetic resonanceguided focused ultrasound mrgfus incisionless procedure capable thermoablation focus multiple acoustic beams although mrgfus currently approved treatment tremor adults safety feasibility profile intracranial lesions pediatric young adult population remains unknownmethods longterm outcomes prospective singlecenter singlearm trial mrgfus nicklaus childrens hospital miami florida presented patients 1522 years age centrally located lesions recruited clinically consistent grade tumors require surgical intervention cohort consisted 4 patients hypothalamic hamartoma hh 1 patient tuberous sclerosis complex harboring subependymal giant cell astrocytoma sega results case highintensity fus used target intracranial lesion realtime mri used monitor thermoablations primary outcomes interest tolerability feasibility safety fus radiographic ablation volume intra postoperative mri also assessed 5 patients tolerated procedure without complications successful thermoablation achieved 4 5 cases calcified sega undertreated due intratumor calcification prevented attainment target ablation temperature hhs underwent target tissue thermoablations led mr signal changes treatment site patients harboring hhs fus thermoablations occurred without procedurerelated complications led improvement seizure control hypothalamic hyperphagia 5 patients discharged home postoperative day 1 2 without readmissions cases hemorrhage electrolyte derangement endocrinopathy new neurological deficit cohortconclusions experience demonstrates fus thermoablation centrally located brain lesions adolescents young adults can performed safely provides therapeutic benefit associated symptomspmid35171812 doi103171 202110jns21416,0.0
pathological observations long spinal cord lesion patient multiple sclerosis neuropathology 2022 feb 15 doi 101111 neup12800 online ahead printabstractwe report autopsy case multiple sclerosis ms manifesting long spinal cord lesion patient japanese woman age 59 years presented onemonth history progressive paraplegia dysesthesia lower extremities urinary retention magnetic resonance imaging revealed long hyperintense lesion t2weighted images extended inferior portion medulla oblongata cervical segments spinal cord isolated lesion t6 level cerebrospinal fluid csf examination revealed presence oligoclonal bands increased myelin basic protein levels 999 pg ml serum antibody aquaporin 4 aqp4 undetectable patient diagnosed atypical ms experienced symptom improvement following immunotherapy corticosteroids plasma exchange died pneumonia renal failure age 62 years postmortem examination revealed long demyelinating lesion extended inferior portion medulla oblongata sacral segments spinal cord lesion comprised numerous demyelinating plaques inflammatory cell infiltration long spinal cord lesion usually indicative neuromyelitis optica spectrum disorder nmosd limited reports postmortem observations long spinal cord lesions among patients antiaqp4 antibodyseronegative ms findings suggest pathomechanisms long spinal cord lesion formation differ antiaqp4 antibodyseronegative ms nmosdpmid35170108 doi101111 neup12800,1.0
obesity adipose tissuederived cytokines pathogenesis multiple sclerosis endocr metab immune disord drug targets 2022 feb 15 doi 102174 1871530322666220215110041 online ahead printabstractmultiple sclerosis ms chronic autoimmune neurodegenerative disease central nervous system cns characterized demyelination neuronal loss permanent neurological impairments etiology ms clearly understood genetics environmental factors can affect susceptibility individuals obesity body mass index bmi 30 kg m2 associated serious health consequences lipid profile abnormalities hypertension type 2 diabetes mellitus reduced levels vitamin d systemic lowgrade inflammatory state can affect cns promote pathogenesis ms due part increased bloodbrain barrier permeability actions adipose tissuederived cytokines adipokines proinflammatory adipokines leptin resistin visfatin crossing bloodbrain barrier activate cnsresident immune cells promote inflammatory responses subsequently demyelinating lesions occur white matter brain spinal cord therefore better knowledge roles adipokines induction obesityrelated chronic inflammation subsequent events leading dysfunctional bloodbrain barrier considerable importance review recent evidence regarding possible roles obesity related systemic lowgrade inflammation well roles adipokines genetic variants modulation immune responses altered bloodbrain barrier permeability ms patients elucidated besides results current studies regarding potential use adipokines predicting ms disease severity response treatment exploredpmid35168514 doi102174 1871530322666220215110041,1.0
exploiting flow cytometry unbiased quantification protein inclusions caenorhabditis elegans j neurochem 2022 feb 15 doi 101111 jnc15591 online ahead printabstractthe aggregation proteins inclusions plaques prominent hallmark diverse range pathologies including neurodegenerative diseases quantification inclusions caenorhabditis elegans models aggregation usually achieved fluorescence microscopy techniques involving biochemical fractionation worm lysates describe simple rapid flow cytometrybased approach allows fluorescentlytagged inclusions enumerated whole worm lysate quantitative unbiased fashion demonstrate technique applicable multiple c elegans models aggregation importantly can used monitor dynamics inclusion formation response heat shock aging includes characterisation physicochemical properties inclusions apparent size may reveal aggregate formation distinct different tissues different stages pathology aging new method can used powerful technique medium highthroughput quantification inclusions future studies genetic chemical modulators aggregation c eleganspmid35170035 doi101111 jnc15591,0.0
multiple sclerosis lesion analysis brain magnetic resonance images techniques clinical applications ieee j biomed health inform 2022 feb 16 pp doi 101109 jbhi20223151741 online ahead printabstractmultiple sclerosis ms chronic inflammatory degenerative disease central nervous system characterized appearance focal lesions white gray matter topographically correlate individual patients neurological symptoms signs magnetic resonance imaging mri provides detailed invivo structural information permitting quantification categorization ms lesions critically inform disease management traditionally ms lesions manually annotated 2d mri slices process inefficient prone inter intraobserver errors recently automated statistical imaging analysis techniques proposed detect segment ms lesions based mri voxel intensity however effectiveness limited heterogeneity mri data acquisition techniques appearance ms lesions learning complex lesion representations directly images deep learning techniques achieved remarkable breakthroughs ms lesion segmentation task provide comprehensive review stateoftheart automatic statistical deeplearning ms segmentation methods discuss current future clinical applications review technical strategies domain adaptation enhance ms lesion segmentation realworld clinical settingspmid35171783 doi101109 jbhi20223151741,0.0
glycogen synthase kinase 3 involvement neuroinflammation neurodegenerative diseases curr med chem 2022 feb 16 doi 102174 0929867329666220216113517 online ahead printabstractbackground gsk3 activity strictly related neuroinflammation neurodegeneration alzheimers disease studied neurodegenerative disease gsk3 seems involved almost neurodegenerative diseases including parkinsons disease amyotrophic lateral sclerosis frontotemporal dementia huntingtons disease autoimmune disease multiple sclerosisobjective aim review help researchers working research topic comprehensive overview gsk3 context neuroinflammation neurodegenerationmethod literature searched using pubmed scifinder databases inserting specific keywords total 500 articles discussedresults first structure regulation kinase briefly discussed specific gsk3 implications neuroinflammation neurodegenerative diseases illustrated also help figures conclude comprehensive overview important gsk3 multitarget inhibitors discussed compounds structure ic50 values target kinase reportedconclusion gsk3 involved several signaling pathways neurons well glial cells immune cells fine regulation interconnection pathways base rationale use gsk3 inhibitors neuroinflammation neurodegeneration fact compounds now clinical trials despite pharmacodynamic adme tox profiles compounds often fully characterized deleterious complex systempmid35170406 doi102174 0929867329666220216113517,0.0
epsteinbarr virus sparks brain autoimmunity multiple sclerosis nature 2022 feb 15 doi 101038 d41586022003822 online ahead printno abstractpmid35169323 doi101038 d41586022003822,0.0
populationbased study nonelective postpartum readmissions women stroke migraine multiple sclerosis myasthenia gravis neurology 2022 feb 15101212 wnl0000000000200007 doi 101212 wnl0000000000200007 online ahead printabstractbackground objectives compare maternal obstetric complications nonelective readmissions women common neurological comorbidities wwn versus women without neurological disordersmethods performed retrospective cohort study index characteristics acute postpartum nonelective rehospitalizations 20152017 national readmissions database using international classification diseases tenth revision codes wald chisquared testing compared baseline demographic hospital clinical characteristics postpartum complications wwn include prior stroke migraine multiple sclerosis ms myasthenia gravis mg controls multivariable logistic regression models examined odds postpartum complications nonelective readmissions within 30 90 days neurological comorbidity compared controls alpha 005 results total 7 612 women prior stroke 83 430 women migraine 6 760 women ms 843 women mg 8 136 335 controls met criteria index admission viable infant delivery wwn likely controls inpatient diagnoses edema proteinuria hypertensive disorders received maternal care poor fetal growth adjusted odds centers disease control prevention cdc severe maternal morbidity indicator smm greater women prior stroke aor 853 95 ci 7241006 migraine aor 204 95 ci 185226 mg aor 445 95 ci 245808 p00001 readmission rates 30 90 days wwn higher controls 30 day prior stroke 29 migraine 17 ms 18 mg 43 controls 11 90 day prior stroke 37 migraine 25 ms 51 mg 60 controls 16 women mg highest adjusted odds readmission 30 days aor 396 95 ci 237665 p00001 90 days aor 330 95 ci 188578 p00001 discussion wwn may higher risk severe maternal morbidity time index delivery postpartum readmission realworld evidence needed develop research infrastructure create efficacious interventions optimize maternalfetal outcomes wwn especially expectant women prior stroke mgpmid35169012 doi101212 wnl0000000000200007,0.0
associations neuropsychiatric symptoms neuropathological diagnoses alzheimer disease related dementias jama psychiatry 2022 feb 16 doi 101001 jamapsychiatry20214363 online ahead printabstractimportance understanding associations alzheimer disease ad related dementias adrd pathologies common neuropsychiatric symptoms nps may implications diagnosis managementobjective evaluate adrd neuropathological diagnoses nps without consideration clinical diagnosisdesign setting participants retrospective cohort study evaluated 1808 brains 39 sites us national alzheimer coordinating center v 10 collection participants among neuropsychiatric inventory questionnaire npiq administered annually brain autopsy diagnoses ad lewy body disease lbd cerebral amyloid angiopathy frontotemporal lobar degeneration cerebrovascular disease hippocampal sclerosis known pathology examined autopsy data collected january 2012 january 2018 deidentified compiled publicly available v 10 database data analyzed february 2021 august 2021main outcomes measures primary outcome npiq domain score present time point mean npiq domain score followup secondary associations adrd diagnoses 12 npiq symptom domains examined regression analyses correcting multiple comparisonsresults study sample 1808 adults mean sd age 800 110 years 987 participants 546 male apathy prevalent nps reaching 80 203 254 individuals hippocampal sclerosis cerebrovascular disease showed nps associations frontotemporal lobar degeneration associated increased apathy increased disinhibition decreased psychosis agitation compared ad hippocampal sclerosis associated increased apathy odds ratio 260 95 ci 186366 false discovery rate controlled p 001 disinhibition odds ratio 215 95 ci 163284 false discovery rate controlled p 001 multiple regression analyses included concomitant neuropathologies main findings remained severe pathology consistently associated increased nps eg lbd associated increase hallucinations brain stem 023 95 ci 007076 p 02 limbic 169 95 ci 127227 p 001 neocortical 449 95 ci 327616 p 001 pathology hallucinations common participants ad lbd 168 534 315 compared ad without lbd 152 704 216 lbd without ad 23 119 196 conclusions relevance cohort study 1808 brains us national alzheimer coordinating center patients lbd ad showed higher prevalence hallucinations compared lbd without ad neuropsychiatric symptom criteria apathy disinhibition behavioral variant frontotemporal lobar degeneration supported study hippocampal sclerosis findings increased apathy disinhibition merit investigation severity neuropathology associated nps severity indicating nps may reflect underlying adrd pathology highlighting importance diagnosing treating npspmid35171235 doi101001 jamapsychiatry20214363,0.0
systematic review selfconcept change multiple sclerosis neuropsychol rehabil 2022 feb 16140 doi 101080 0960201120222030367 online ahead printabstractselfconcept sense self often altered context neurological illness yet core aspects subjective experience poorly understood people multiple sclerosis ms systematic review aimed synthesize findings quantitative qualitative studies investigating selfconcept ms psycinfo medline pubmed cinahl scopus web science last systematically searched may 2021 mixed methods appraisal tool consolidated criteria reporting qualiatative research used appraise quality eligible articles articles included measured explored selfconcept ms populations published english peerreviewed total 30 studies 11 quantitative 19 qualitative identified quantitative studies synthesized using narrative approach results suggesting ms associated degree selfconcept change qualitative studies synthesized using thematic synthesis results illustrating complex process selfconcept change catalyzed msrelated events characterized varying degrees resistance acknowledgement changes future prospective longitudinal studies needed characterize nature selfconcept change ms using validated tools measure relevant aspects selfconcept ms populationpmid35168496 doi101080 0960201120222030367,0.0
deep learningbased toolbox automated limb motion analysis alma murine models neurological disorders commun biol 2022 feb 15 5 1 131 doi 101038 s42003022030776abstractin neuroscience research refined analysis rodent locomotion complex cumbersome access technique limited necessity expensive equipment study implemented new deep learningbased opensource toolbox automated limb motion analysis alma requires basic behavioral equipment inexpensive camera alma toolbox enables consistent comprehensive analyses locomotor kinematics paw placement can applied neurological conditions affecting brain spinal cord demonstrated alma toolbox can 1 robustly track evolution locomotor deficits spinal cord injury 2 sensitively detect locomotor abnormalities traumatic brain injury 3 correctly predict disease onset multiple sclerosis model therefore established broadly applicable automated standardized approach requires minimal financial time commitments facilitate comprehensive analysis locomotion rodent disease modelspmid35169263 doi101038 s42003022030776,0.0
immunological predictors dimethyl fumarateinduced lymphopenia ann neurol 2022 feb 16 doi 101002 ana26328 online ahead printabstractobjective treatment dimethyl fumarate dmf leads lymphopenia infectious complications subset patients multiple sclerosis ms aimed reveal immune markers dmfassociated lymphopeniamethods prospective observational study longitudinally assessed 31 individuals ms singlecell mass cytometry 12 48 weeks dmf therapyresults employing neural networkbased representation learning approach identified ccr4expressing t helper cell population negatively associated relevant lymphopeniainterpretation ccr4expressing t helper cells represent candidate prognostic biomarker development relevant lymphopenia patients undergoing dmf treatment article protected copyright rights reservedpmid35170072 doi101002 ana26328,0.0
myelin oligodendrocyte glycoprotein antibodyassociated optic neuritis update arq bras oftalmol 2022 feb 14s000427492022005003210 doi 105935 0004274920230012 online ahead printabstractmyelin oligodendrocyte glycoproteinimmunoglobulin g igg associated optic neuritis established new entity immunemediated optic neuropathy patients usually present recurrent optic neuritis often bilaterally initially severe vision loss optic disc edema however contrast aquaporin 4iggseropositive neuromyelitis optica spectrum disorder visual recovery tends favorable good response steroid treatment another important differential diagnosis myelin oligodendrocyte glycoproteiniggassociated optic neuritis multiple sclerosis close monitoring signs relapse longterm immunosuppression may considered maintain optimal visual function diagnosis can made basis presence specific usually serological antibody myelin oligodendrocyte glycoprotein igg cellbased assay demyelinating event optic neuritis myelitis brainstem syndrome cortical lesions seizures clinical spectrum newly recognized inflammatory demyelinating disease expanding rapidly briefly review epidemiological characteristics clinical manifestations diagnostic considerations treatment options myelin oligodendrocyte glycoproteiniggassociated optic neuritispmid35170658 doi105935 0004274920230012,1.0
predictors glucocorticoid use acute optic neuritis united states 20052019 ophthalmic epidemiol 2022 feb 1617 doi 101080 0928658620222034167 online ahead printabstractpurpose acute optic neuritis variably treated glucocorticoids aimed describe factors associated glucocorticoid usemethods retrospective longitudinal cohort study insured patients united states 20052019 adults 1850 years old one inpatient 2 outpatient diagnoses within 90 days included glucocorticoid use classified none dose highdose 100 mg prednisone equivalent 1 days primary outcome glucocorticoid receipt within 90 days first diagnosis multivariable logistic regression models assessed relationship glucocorticoid use sociodemographics comorbidities clinician specialty visit number yearresults 3026 people 658 women n 1991 median age interquartile range 38 years 31 44 686 white n 2075 glucocorticoids received 46 n 1385 546 n 760 1385 received highdose odds receiving glucocorticoids higher among patients multiple sclerosis 161 95ci 128204 p 001 mri 175 95ci 109280 p 02 3 180 95ci 146222 p 001 408 95ci 337495 p 001 outpatient visits certain regions compared ophthalmologists patients diagnosed neurologists 136 95ci 110169 p 005 emergency medicine 397 95ci 266594 p 001 inpatient clinicians 294 95ci 222390 p 001 higher odds receiving glucocorticoids use increased 11 annually p 001 conclusions demyelinating disease care intensity setting region clinician type associated glucocorticoid use optimize care future studies explore reasons care variation patient clinician preferencespmid35168450 doi101080 0928658620222034167,1.0
subependymal giant cell astrocytoma tuberous sclerosis complex tscsega shinkei geka 2022 jan 50 1 111121 doi 1011477 mf1436204536abstractsubependymal giant cell astrocytoma sega lowgrade brain tumor occurring specifically patients tuberous sclerosis complex tsc tsc autosomal dominant genetic disease affecting multiple body systems wide variability presentation sega usually arises around caudothalamic groove near foramen monro can therefore cause lifethreatening complications due hydrocephalus sega develops due complete loss function tsc1 tsc2 complex twohit mechanism biallelic inactivation tsc1 tsc2 gene leading activation mammalian target rapamycin mtor identification pathogenic variant tsc1 tsc2 sufficient diagnosis tsc individuals segas presenting acute deterioration due obstructive hydrocephalus undergo urgent surgical treatment mtor inhibitors shown prevent sega growth patients tsc treatment mtor inhibitors primarily recommended individuals nonacute symptomatic asymptomatic growing large segas surgical candidates prefer medical treatment surgery longterm treatment mtor inhibitors efficiently reduced segas prevented hydrocephalus surgical risks potential side effects mtor inhibitors effect tsc manifestations considered best treatment option selectedpmid35169091 doi1011477 mf1436204536,0.0
increased oxidative stress contributes impaired peripheral cd56dimcd57+ nk cells patients systemic lupus erythematosus background systemic lupus erythematosus sle characterized loss immune tolerance imbalance immune cell subsets natural killer nk cells contribute regulate innate adaptive immune response study aimed detect alterations peripheral nk cells explore intrinsic mechanisms involving nk cell abnormality slemethodsblood samples healthy controls hcs patients sle rheumatoid arthritis ra collected nk count nk subsets cd56bright cd56dimcd57 cd56dimcd57+ phenotypes apoptosis evaluated flow cytometer mitochondrial reactive oxygen species mtros total ros levels detected mitosox red dcfhda staining respectively published data gse63829 gse23695 gene expression omnibus geo analyzed gene set enrichment analysis gsea resultstotal peripheral nk count downregulated untreated sle patients comparison untreated ra patients hcs sle patients exhibited selective reduction peripheral cd56dimcd57+ nk cell proportion negatively associated disease activity positively correlated levels complement c 3 c4 compared hcs peripheral cd56dimcd57+ nk cells sle patients exhibited altered phenotypes increased endogenous apoptosis higher levels mtros ros addition treated hydrogen peroxide h2o2 peripheral cd56dimcd57+ nk cell subset prone undergo apoptosis cd56dimcd57 nk cells furthermore nk cell subset sle patients exhibited impaired cytotoxicity response activated cd4+ t cells vitroconclusionour study demonstrated selective loss mature cd56dimcd57+ nk cell subset sle patients may caused preferential apoptosis subset increased oxidative stress sle attenuated vitro cytotoxicity cd56dimcd57+ nk cells may contribute impaired ability eliminating pathogenic cd4+ t cells sle,0.0
structural functional foot disorders patients genodermatoses singlecentre retrospective chart review background skin lesions feet foot deformities impair daily activities decrease quality life although substantial foot deformities occur many genodermatoses reports published topic therefore performed retrospective chart review identify patients genodermatoses foot disorders included 16 patients investigated clinically molecular biologyresultsthe following genodermatoses foot deformities detected autosomal recessive congenital ichthyosis arci n 7 palmoplantar keratodermas ppks n 6 ichthyosis follicularis atrichia photophobia ifap n 1 ectrodactylyectodermal dysplasiaclefting eec n 1 ichthyosis confetti iwc n 1 foot problems varied severity depending disease also showed phenotypic heterogeneity among patients condition foot deformities pronounced patients eec split foot iwc contractures less severe arci clawed toes ifap hollow feet ppk bone abnormalities feet conclusionbecause range distinct genodermatoses involve foot abnormalities early rehabilitation corrective measures provided patients foot involvement improve gait prevent delay irreversible complications,0.0
possible implement rare disease casefinding tool primary care ukbased pilot study abstractintroductionthis study implemented mendelscan primary care rare disease casefinding tool uk national health service population rare disease diagnosis challenging due disease complexity low physician awareness 2021 uk rare diseases framework highlights key priority need faster diagnosis improve clinical outcomes methods resultsa uk primary care locality 68 705 patients examined mendelscan encodes diagnostic screening criteria multiple rare diseases mapping clinical terms appropriate snomed ct codes uk primary care standardised clinical terminology create digital algorithms algorithms applied pseudoanonymised structured data extract electronic health records ehr locality flag atrisk patients may require evaluation flagged patients underwent internal clinical review doctor reviewing ehr flagged algorithm removing cases clear diagnosis diagnoses explains clinical features led patient flagged passed review report returned gp 55 76 disease criteria flagged least one patient 227 033 total 68 705 ehr flagged 18 ehr already diagnosed disease highlighted ehr diagnostic code rd screened eg behcets disease algorithm identifying ehr snomed ct code behcets disease 75 227 33 ehr passed internal review thirtysix reports returned gp feedback available 28 36 reports sent gp categorised nine reports reasonable possible diagnosis advance investigation six reports diagnosis already excluded ten reports patient clear alternative aetiology three reports patient left study locality unable reidentify accurately 9 cases considered reasonable possible diagnosis evaluationconclusionsthis pilot demonstrates implementing tool feasible population level casefinding tool identified credible cases subsequently referred investigation future work includes performancebased validation studies diagnostic algorithms scalability tool,0.0
wholebrain metabolic abnormalities associated mobility older adults multiple sclerosis neurorehabil neural repair 2022 feb 1415459683221076461 doi 101177 15459683221076461 online ahead printabstractbackground older adults multiple sclerosis ms experience mobility impairments conventional brain imaging poor predictor walking abilities populationobjective test whether brain metabolites measured magnetic resonance spectroscopy mrs associated walking performance older adults msmethods fifteen older adults ms mean age 609 sd 51 22 agematched healthy controls mean age 642 sd 57 underwent wholebrain mrs mobility testing levels nacetylaspartate naa myoinositol mi choline cho temperature 47 brain regions compared groups correlated walking speed timed 25 foot walk walking endurance sixminute walk results older adults ms higher mi 23 areas including bilateral frontal right t 21449 2605 p 016 left t 35 2434 p 020 temporal right t 35 3063 p 004 left t 35 3026 p 005 parietal lobes right t 21100 2886 p 009 left t 35 2507 p 017 right thalamus t 35 2840 p 007 mi eleven regions correlated walking speed mi twelve regions correlated walking endurance naa lower ms bilateral thalami right t 35 3449 p 001 left t 35 2061 p 047 caudate nuclei right t 33 2828 p 008 left t 32 2132 p 041 posterior cingulum right t 35 3077 p 004 left t 35 2972 p 005 naa four regions correlated walking speed endurance brain temperature higher ms patients four regions correlate mobility measures group differences choconclusion mi naa may useful imaging endpoints walking ability clinical outcome older adults mspmid35164595 doi101177 15459683221076461,0.0
kirenol potential natural lead molecule new drug design development therapy inflammation molecules 2022 jan 23 27 3 734 doi 103390 molecules27030734abstractkirenol potential natural diterpenoid molecule mainly found sigesbeckia species kirenol received lot interest recent years due wide range pharmacological actions particular significant ability interact wide range molecular targets associated inflammation review summarise efficacy safety kirenol reducing inflammation well potential mechanisms action opportunities future drug development based preclinical studies reported earlier kirenol good therapeutic potential inflammation involved multiple sclerosis inflammatory bowel disorders diabetic wounds arthritis cardiovascular disease bone damage joint disorders also address physicochemical druglike features kirenol well structurally modified kirenolderived molecules inhibition proinflammatory cytokines reduction nuclear factor kappab nfb attenuation antioxidant enzymes stimulation hemeoxygenase1 ho1 expression nuclear factor erythroid 2related factor 2 nrf2 phosphorylation among molecular mechanisms contributing kirenols antiinflammatory actions furthermore review also highlights challenges opportunities improve drug delivery kirenol treating inflammation according findings review kirenol active molecule inflammation numerous preclinical models indicating path using new drug discovery development treatment wide range inflammationspmid35163999 doi103390 molecules27030734,0.0
targeting neurological comorbidities multiple sclerosis beneficial effects vip pacap neuropeptides j integr neurosci 2022 jan 28 21 1 33 doi 1031083 jjin2101033abstractvasoactive intestinal peptide vip pituitary adenylate cyclaseactivating polypeptide pacap two widely expressed neuropeptides important immunomodulatory neuroprotective properties central nervous system cns vip pacap implicated several neurological diseases shown favourable effects different animal models multiple sclerosis ms ms chronic inflammatory neurodegenerative disease cns affecting 25 million people worldwide disease characterised extensive neuroinflammation demyelination axonal loss currently cure ms treatment options displaying partial efficacy importantly epidemiological studies ms population demonstrated high incidence neurological psychological comorbidities depression anxiety epilepsy stroke among afflicted people hence given widespread protective effects vip pacap system cns review will aim exploring beneficial roles vip pacap ameliorating common neurological comorbidities associated ms final scope review put emphasis targeting vip pacap system may effective therapeutic strategy modify ms disease course associated comorbiditiespmid35164469 doi1031083 jjin2101033,1.0
bacillus calmetteguerin vaccination multiple sclerosis populationbased birth cohort study quebec canada eur j neurol 2022 feb 15 doi 101111 ene15290 online ahead printabstractbackground bacillus calmetteguerin bcg vaccine reduce incidence multiple sclerosis ms immunomodulation previous studies presenting limitations reported association reexamined association large cohort focusing relapsingremitting ms rrms methods cohort included 400 563 individuals linked quebec provincial bcg vaccination registry administrative health data individuals followedup 1983 2014 within period 1 19831996 period 2 19972014 occurrence ms incident ms cases defined 3 hospital physician claims ms subjects 1 drug reimbursement ms diseasemodifying therapies classified rrms cox proportional hazards regression used estimate hazard ratios hr followups adjusting potential confounders possible effect modification due sex assessedresults total 178 335 46 individuals bcg vaccinated 274 006 incident ms cases identified 19831996 1 433 04 19972014 association found rrms either period 1 adjusted hrs 096 95 confidence interval 063145 96 cases period 2 hradj 102 085123 480 cases remaining ms cases phenotype unknown positively associated bcg entire followup hradj 125 110141 1 131 cases period 2 hradj133 117152 953 cases interaction sex foundconclusion findings suggest bcg vaccination decrease risk rrms future studies consider phenotypes mspmid35165983 doi101111 ene15290,0.0
brain grey matter perfusion primary progressive multiple sclerosis mild decrease years regional associations cognition hand function eur j neurol 2022 feb 15 doi 101111 ene15289 online ahead printabstractbackground extend dynamic neurodegeneration progressive multiple sclerosis ms might reflected global regional brain perfusion outcome intercept structure function provide first insight evolution brain perfusion association disability primary progressive ms ppms several yearsmethods 77 persons ppms followed 5 years visits included 3t mri pulsed arterial spin labelling asl perfusion timed25footwalk 9holepegtest nhpt symboldigitmodalitiestest sdmt expanded disability status scale edss extracted regional cerebral blood flow surrogates compared 11 controls analyses focused cortical deep gray matter change time associations disability regional global levelresults baseline brain perfusion patients controls comparable cortex p0716 deep grey matter p0095 edss disability increased mildly p0023 brain perfusion decreased follow p0001 disease duration p0009 lower global perfusion correlated higher disability indicated edss nhpt timed25footwalk p0001 motor task nhpt showed associations twenty gray matter regions contrast better sdmt performance correlated lower perfusion p0001 seven predominantly frontal regions indicating functional maladaptationconclusion decreasing perfusion indicates putative association ms disease mechanisms neurodegeneration reduced metabolism loss resilience low alteration rate limits use clinical practice regional association patterns might provide snapshot adaptive maladaptive functional reorganizationpmid35167161 doi101111 ene15289,0.0
new oligodendrocytes exhibit abundant accurate myelin regeneration survive demyelination nat neurosci 2022 feb 14 doi 101038 s4159302101009x online ahead printabstractoligodendrocytes survive demyelination can remyelinate including multiple sclerosis ms unclear study using zebrafish found surviving oligodendrocytes make new sheaths frequently mistarget new myelin neuronal cell bodies pathology also found ms contrast oligodendrocytes generated demyelination make abundant correctly targeted sheaths indicating likely also better regenerative potential mspmid35165460 doi101038 s4159302101009x,1.0
impact australian black summer bushfires covid19 pandemic wellbeing persons multiple sclerosis preparation future ongoing crises disabil rehabil 2022 feb 15114 doi 101080 0963828820222037756 online ahead printabstractpurpose australian multiple sclerosis ms community experienced two recent major crises widespread bushfires covid 19 pandemic aimed understand needs persons ms times crisismaterials methods consumerdirected mixedmethod study included online survey semistructured interviews workshop persons ms carers healthcare professionals disability advocates data collected via 1 176 people completing online surveys identify crisis concerns communications 2 29 people completing online interviews bushfire pandemic impact 3 13 people participating crisespriorities workshop descriptive data calculated survey response general inductive analytical approach taken interview workshop responsesresults significant concerns bushfire smoke exposure diseasemodifyingmedication susceptibility covid19 66 63 mean concern score respectively interviews indicated crises experiences bushfires pandemic overlapped respective changes mood symptom stability bushfires need future preparations pandemic benefits social restrictions disclosing personal health information increased care burden importantconclusions multiple crises challenged ms community offered lessons healthcare future crises continued progress centralised crisis information considered use telehealth rural healthcare support neededimplications rehabilitationthe ms community showed high concerns effect toxic smoke 2019 2020 australian bushfires separately diseasemodifyingmedication susceptibility covid19the ms community placed priority crisis management plan individualsreduced social activity due restrictions beneficial ms symptom selfawareness may help overall fatigue managementhealthcare system preparation must prepare alleviate increased carer workload times crisispmid35166613 doi101080 0963828820222037756,0.0
eagle syndrome rare cause stroke young patient cureus 2022 jan 11 14 1 e21102 doi 107759 cureus21102 ecollection 2022 janabstractstroke common acute neurological injury may develop due arterial thrombosis hemorrhage however uncommon young population etiologies stroke young patients different compared elderly population include various nonatherosclerotic angiopathies hematological conditions inflammatory disorders report case 26yearold man presented emergency department noticed right hand become clumsy first noticed symptom five days presentation noticed symptom improved significantly since began reported episodes neck pain pain around ear visited family physician clinic several times complaint diagnosed temporomandibular joint disorder neurological examination revealed decreased muscle strength right upper limb power 4 5 along sensory deficit coordination intact gait ataxia noted considering patients age initial diagnosis demyelinating disorder multiple sclerosis patient underwent magnetic resonance imaging brain demonstrated increased signal intensity territory left middle cerebral artery representing leftsided infarction subsequently patient underwent computed tomography angiography head rule structural malformation scan showed presence elongated styloid process appeared close proximity neck vasculature radiological findings consistent eagle syndrome patient underwent surgical resection styloid process eagle syndrome rare clinical condition may myriad clinical presentations high index suspicion condition vital reach diagnosis physicians keep condition differential diagnosis stroke young population risk factorspmid35165561 pmcpmc8829662 doi107759 cureus21102,1.0
healthy properties new formulation pomegranatepeel extract mice suffering experimental autoimmune encephalomyelitis molecules 2022 jan 28 27 3 914 doi 103390 molecules27030914abstracta new formulation pomegranatepeel extract pem obtained puae pulsed ultrasoundassisted extraction titrated ellagic acid ea punicalagin proposed characterized analyzed potential health properties mice suffering experimental autoimmune encephalomyelitis eae pem effects compared elicited formulation containing ea eam control eae mice chronically administered eam pem dissolved drinking water starting day 10 postimmunization dpi therapeutic protocol deliver daily 50 mg kg ea treated eae mice limit daily access beverage show changes body weight displayed significant amelioration vivo clinical symptoms ex vivo histochemical analysis showed spinalcord demyelination inflammation pem eamtreated eae mice 23 1 dpi comparable untreated eae animals microglia activation measured ionized calcium binding adaptor 1 iba1 staining astrocytosis quantified glial fibrillar acid protein gfap immunopositivity significantly recovered particularly gray matter eam pem displayed comparable efficiencies controlling spinal pathological cellular hallmarks eae mice support delivery dietary supplementation patients suffering multiple sclerosis ms pmid35164175 doi103390 molecules27030914,1.0
thematic analysis multiple sclerosis research enhanced strategic diagram mult scler 2022 feb 1513524585221075542 doi 101177 13524585221075542 online ahead printabstractrecent interest multiple sclerosis research warrants literature analysis evaluate current state discipline new research domains bibliometric review summarised research trends analysed research areas multiple sclerosis last decade documents containing term multiple sclerosis article title retrieved scopus database used harzings publish perish vosviewer citation analysis data visualisation respectively found total 18 003 articles published journals english language 2012 2021 emerging keywords identified utilising enhanced strategic diagram covid19 teriflunomide clinical trial microglia b cells myelin brain white matter functional connectivity pain employment healthrelated quality life metaanalysis comorbidity study demonstrates tremendous growth multiple sclerosis literature worldwide expected grow double next decade especially identified emerging topicspmid35164590 doi101177 13524585221075542,1.0
management hepatitis b virus prophylaxis patients treated diseasemodifying therapies multiple sclerosis multicentric italian retrospective study j neurol 2022 feb 14 doi 101007 s0041502211009x online ahead printabstractbackground patients multiple sclerosis ms often receive diseasemodifying therapies dmts can expose reactivation potential occult hepatitis b virus hbv infection pobi aimed evaluate ms centers behavior regarding hbv screening prophylaxis large cohort ms patients receiving anticd20 cladribinemethods retrospective multicentric study recruiting italian ms patients treated rituximab ocrelizumab cladribineresults included 931 ms patients 15 centers 38 patients performed complete hbv screening patients age 50 years significantly associated history vaccination hbsab titres 100 miu baseline p 0001 significant correlation found postvaccination hbsab titres type treatment p 05 preor posttherapy vaccination p 02 number previous dmts p 02 among pobi patients n 53 21 received antiviral prophylaxis 13 hbv dna monitoring 19 patients neither monitored hbv dna received prophylaxisconclusions baseline hbv screening patients receiving anticd20 cladribine consolidated practice nonetheless hbv vaccination coverage still lacking population age significant factor associated low hbv protection rituximab ocrelizumab cladribine impair hbv vaccine response almost 35 pobi patients fail receive hbvr prevention management hbv prophylaxis improved ms patients prospective studies needed assess effectiveness prophylactic strategies patientspmid35165767 doi101007 s0041502211009x,0.0
identification corosolic oleanolic acids molecules antagonizing human rort nuclear receptor using calculated fingerprints molecular similarity int j mol sci 2022 feb 8 23 3 1906 doi 103390 ijms23031906abstractrort protein product rorc gene belonging nuclear receptor subfamily retinoicacidreceptorrelated orphan receptors rors rort preferentially expressed th17 lymphocytes drives differentiation naive cd4+ cells involved regulation expression numerous th17specific cytokines il17 th17 cells implicated pathology autoimmune diseases eg psoriasis inflammatory bowel disease multiple sclerosis rort whose activity regulated ligands recognized drug target potential therapies diseases identification ligands timeconsuming usually requires screening chemical libraries herein using tanimoto similarity search found corosolic acid pentacyclic tritepenes library previously screened compounds highly similar rort inverse agonist ursolic acid furthermore using gene reporter assays th17 lymphocytes distinguished compounds exert stronger biological effects ursolic corosolic oleanolic acid ineffective asiatic maslinic acids providing evidence combinatorial methodology silico experimental might help wet screenings achieve accurate results eliminating false negativespmid35163824 doi103390 ijms23031906,0.0
neuroprotective effects icariin ageing various neurological neuropsychiatric disorders brain injury induced radiation exposure aging albany ny 2022 feb 14 14 undefined doi 1018632 aging203893 online ahead printabstractepimedium brevicornum maxim traditional chinese medicine used treatment impotence sinew bone disorders painful impediment caused winddampness numbness spasms hypertension coronary heart disease menopausal syndrome bronchitis neurasthenia many years china recent animal experimental studies indicate icariin major bioactive component epimedium may effectively treat alzheimers disease cerebral ischemia depression parkinsons disease multiple sclerosis well delay ageing recent study also suggested epimedium extract exhibit radioneuroprotective effects prevent ionizing radiationinduced impairment neurogenesis paper reviewed pharmacodynamics icariin treating different neurodegenerative neuropsychiatric diseases ageing radiationinduced brain damage relevant molecular mechanisms antineuroinflammatory antiapoptotic antioxidant well proneurogenesis roles also discussedpmid35165207 doi1018632 aging203893,1.0
clinical neurophysiological patterns impairments emotion attention empathy multiple sclerosis j integr neurosci 2022 jan 28 21 1 7 doi 1031083 jjin2101007abstractpatients suffering multiple sclerosis experience various cognitive affective impairments resulting negative impact social behavior personal independence differing degrees according often clinically subtle conflicting cognitiveaffective impairments recordings socially relevant issues still demand stratifying clinical social support sophisticated way therefore studied specific cognitive affective capacities eleven patients predominant relapsingremitting type multiple sclerosis applying paradigms eventrelated potentials wellselected neuropsychological test protocol thus far distinct cognitive disturbances executive attentional domains wechsler memory tests four memory indices found multiple sclerosis patients concerning affective domains patients showed discrete impairments affect discrimination affected naming proved specific testing tuebinger affect battery neurophysiologically eventrelated potentials recordings multiple sclerosis patients associated decreased implicit emotion processing cues different emotion arousal early processing stage depending attentional capacities alterations implicit emotion modulation late processing stages clinical neurophysiological neuropsychological data correlated part quantitative magnetic resonance imaging brain lesions summarizing data data indicate certain neurocognitive neuroaffective dysfunctions patients multiple sclerosis thus highlighting validity sensitive recording less apparent neurologic disturbances multiple sclerosis optimizing individual care management patientspmid35164443 doi1031083 jjin2101007,0.0
sensorbased gait analyses sixminute walk test identify qualitative improvement gait parameters people multiple sclerosis rehabilitation j neurol 2022 feb 15 doi 101007 s0041502210998z online ahead printabstractthe aim work determine whether wearable inertial measurement units imus detect gait improvements across different disability groups people multiple sclerosis pwms sixminute walk test 6mwt rehabilitation stay specialized rehabilitation center fortysix pwms 20 healthy controls hc included study performed 6mwt two inertial measurement units imus placed feet thirtytwo pwms retested end stay pwms divided milddisability moderatedisability group 6mwt divided six sections 1 min technical analysis linear mixed models used statistical analyses comparison two disability groups hc highlighted significant differences gait parameter p 0001 crossing effect testretest two disability groups showed greater improvement moderatedisability group finally gait parameter higher effect size allowing best differentiation disability groups foot flat ratio r2 053 gait analyses wearable sensors identified different evolutions gait patterns 6mwt pwms different physical disability measured effect shorttime rehabilitation gait 6mwt higher pwms higher degree disability using imus clinical setting allowed identify significant changes interstride gait patterns wearable sensors key parameters potential useful clinical tools focusing gait pwmspmid35166925 doi101007 s0041502210998z,0.0
characterizing time course cerebrovascular reactivity multiple sclerosis j neuroimaging 2022 feb 14 doi 101111 jon12979 online ahead printabstractbackground purpose changes cerebral perfusion occur early relapsing progressive multiple sclerosis ms patients though whether cerebral blood flow cbf can altered therapy unknown sought characterize time course change cbf cerebral vascular reactivity cvr following intravenous iv acetazolamide acz whole brain within various gray white matter brain regions ms patientsmethods enrolled five relapsing ms patients injectable therapies participants received 1000 mg iv bolus acz cbf measured using pseudocontinuous arterial spin labeling mri quantify differences time course patients calculated numerical integration cvr time using trapezoidal rule estimate area curve auc cvr results change whole brain cbf 3065 seen participants 15 minutes acz challenge cbf increases 20 baseline sustained 90 minutes within wholebrain normalappearing white matter total t2hyperintense lesioned tissue auc cvr values gray cortical deep gray matter white normalappearing t2lesioned matter regions similar patientsconclusion findings show prolonged time course vascular reactivity acz stimulus ms patients similar time course gray white matter brain regions including previously injured tissue preliminary results suggest blood flow can augmented established ms lesion suggesting even previously injured tissue might responsive treatmentpmid35165962 doi101111 jon12979,0.0
dietary habits nutritional status risk first demyelinating event incident casecontrol study southern european cohort neurol sci 2022 feb 15 doi 101007 s10072022059080 online ahead printabstractbackground relationship dietary habits multiple sclerosis ms risk still controversial studies involved populations scandinavia north america australia data populations southern europe area high ms prevalence scarceobjective examine association dietary habits nutritional status risk first demyelinating event southern european incident cohortmethods incident casecontrol study detailed nutritional assessment performed registered dietitian patients first demyelinating event age sexmatched controls body composition analysis anthropometric evaluation blood tests nutritional status also performedresults eightythree patients first demyelinating event prospectively recruited 1year period low intake fibers 0846 p 0014 vitamin d 0730 p 00001 alphalinolenic acid 0283 p 0014 high bmi 1132 p 0028 ever smoker status 4472 p 0003 independently associated risk first demyelinating event higher intake rapid absorption carbohydrates lower intake vegetal proteins higher intake animal proteins observed patients first demyelinating eventconclusions significant differences patients controls observed dietary habits time first demyelinating event suggesting low intake fibers vitamin d alphalinolenic acid main dietary risk factors furthermore high cardiovascular risk dietary habits frequent time ms onset suggesting usefulness nutritional intervention part activities ms centerspmid35166977 doi101007 s10072022059080,1.0
neuropsychological correlates cerebellar volumes multiple sclerosis mri volumetric analysis study j integr neurosci 2022 jan 28 21 1 13 doi 1031083 jjin2101013abstractthe hallmark multiple sclerosis ms pathophysiology damage myelin sheath around axons cerebellum predilection site demyelination wellrecognized role motor rather understudied contribution cognitive functions aim study investigate patterns cerebellar grey white matter pathology expressed reduced volume well cortical thickness potential contribution cognitive performance disability status patients ms 24 patients ms underwent extensive neuropsychological assessment using paper pencil tests brain health assessment bha tabletbased battery cerebellar lobular volumes thickness calculated using volumetric analysis automated segmentation cerebellum lobules main findings reduction cerebellar grey matter cgmv white matter volumes cwmv lobule x widespread cerebellar cortical thinning patients overall disease severity neurological disability assessed expanded disability status severity scale correlated fatigue information processing speed tasks cgmv cwmv cwmv cgmv lobule iii negatively correlated information processing speed well visuospatial memory tests finally inverse cortical thinning associations noted whole cerebellum lobule iii lobule iii lobule vi crus lobule viiia information processing speed verbal fluency tasks inverse associations observed may represent compensatory mechanism activated ms engaging additional highlevel cortical areas functionally interconnected damaged cerebellum order cope cognitive demands taskpmid35164449 doi1031083 jjin2101013,1.0
cortical white matter lesion topology influences focal corpus callosum atrophy multiple sclerosis j neuroimaging 2022 feb 14 doi 101111 jon12977 online ahead printabstractbackground purpose corpus callosum cc atrophy strong predictor multiple sclerosis ms disability contributing pathological mechanisms remain uncertain aimed apply advanced mri explore drives often nonuniform callosal atrophymethods prospective brain 7 tesla 3 tesla human connectom scanner mri performed 92 ms patients white matter leukocortical intracortical lesions manually segmented freesurfer used segment cc topographically classify lesions per lobe deep white matter lesions regression models calculated predict focal cc atrophyresults frontal parietal lobes contained majority 80 lesion classifications relapsingremitting secondary progressive ms subtypes anterior subsection cc smallest proportional volume difference subtypes 11 deep temporal occipital white matter lesions occipital intracortical lesions strongest predictors middleposterior callosal atrophy adjusted r2 5439 p 01 conclusions white matter cortical lesions contribute regional corpus callosal atrophy lobespecific lesion topology fully explain inhomogeneous cc atrophypmid35165979 doi101111 jon12977,0.0
human herpesvirus 6 infection trigger multiple sclerosis update recent literature background update existing evidence regarding relationship infection human herpesvirus 6 hhv6 multiple sclerosis ms order contribute attempt define nature strength relationshipresultsstudy quality assessed using criteria proposed moore wolfson classification criteria used canadian task force periodic health examination studies categorized experimental technique quality high intermediate b low c determined moore wolfson criteria overall 27 90 30 studies 18 86 classified quality reached statistically significant result according canadian task force classification studies categorized evidence qualityii1 limitations available experimental techniques perspectives future research discussedconclusionsthe current review continues emphasize need objective evidencebased examination relationship hhv6 infection multiple sclerosis,0.0
application wharton jellyderived mesenchymal stem cells patients pulmonary fibrosis abstractpulmonary fibrosis devastating disease eventually leads death respiratory failure despite wide range drugs including corticosteroids endothelin antagonist pirfenidone effective treatment main goal treatment alleviate symptoms much possible slow progression disease improve quality life lung transplantation may treatment option people pulmonary fibrosis develops established treatment pulmonary fibrosis caused covid19 virus another problem face patients despite efforts international medical communities therefore achieving alternative treatment patients great success today basic research using stem cells pulmonary fibrosis published promising results new stem cellbased therapies can helpful patients pulmonary fibrosis wharton jellyderived mesenchymal stem cells easily isolated large quantities made available clinical trials without causing ethical problems cells higher flexibility proliferation potential cells isolated different sources differentiated various cells laboratory environments clinical trials needed determine safety efficacy cells study will investigate cellular molecular mechanisms possible effects wharton jellyderived mesenchymal stem cells pulmonary fibrosis,0.0
characterization dna methylation well micorna expression screening epigenetic markers adipogenesis abstractthis study aimed use bioinformatics methods characterize epigenetic changes terms microrna mirna expression dna methylation adipogenesis mrna mirna expression microarray dna methylation dataset obtained geo database differentially expressed genes degs differentially expressed mirnas dems differentially methylated probes dmps filtered using limma package r language cluster profile package used functional enrichment analysis proteinprotein interaction ppi network constructed using string visualized cytoscape connection map cmap website tool used screen potential therapeutic drugs adipogenesis comparing early late stages adipogenesis 111 low mirna targeted upregulated genes 64 high mirna targeted downregulated genes obtained well 663 lowmethylated highexpressed genes 237 highmethylated lowexpressed genes addition 41 genes 24 upregulated 17 downregulated simultaneously regulated abnormal mirna changes dna methylation ten chemicals identified putative therapeutics adipogenesis addition among dualregulated genes identified canx hnrnpa1 mcl1 ppif may play key roles epigenetic regulation adipogenesis may serve aberrant methylation mirna targeting biomarkers,0.0
prediction liquidliquid phase separating proteins using machine learning background liquidliquid phase separation llps biomolecules cell underpins formation membraneless organelles condensates protein nucleic acid play critical roles cellular function dysregulation llps implicated number diseases although llps biomolecules investigated intensively recent years knowledge prevalence distribution phase separation proteins psps still lag behind development computational methods predict psps therefore great importance comprehensive understanding biological function llps resultsbased psps collected llpsdb developed sequencebased prediction tool llps proteins pspredictor attempt general purpose psp prediction depend specific protein types method combines componential sequential information protein embedding stage adopts machine learning algorithm final predicting proposed method achieves tenfold crossvalidation accuracy 9471 outperforms previously reported psps prediction tools applications built userfriendly pspredictor web server http wwwpkumdlcn pspredictor accessible prediction potential psps conclusionspspredictor identifie novel scaffold proteins stress granules predict psps candidates human genome study applications built userfriendly pspredictor web server http wwwpkumdlcn pspredictor provides valuable information potential psps recognition,0.0
nicotinic acetylcholine receptors expressed striatal interneurons inhibit striatal activity control striataldependent behaviors acetylcholine important modulator striatal activity vital controlling striataldependent behaviors including motor cognitive functions despite significance mechanisms determining acetylcholine impacts striatal signaling still fully understood particular little known role nicotinic acetylcholine receptors nachrs expressed striatal interneurons present study used fluorescent situ hybridization fish determine neuronal types express prevalent beta2 nicotinic subunit mouse striatum data support common view nachr expression mostly restricted striatal interneurons surprisingly though cholinergic interneurons cins identified population highest expression beta2 nicotinic subunit investigate functional significance beta2containing nachrs striatal interneurons deleted injecting aavcre vector striatum beta2flox flox male mice deletion led alterations several behavioral domains namely increased anxietylike behavior decrease sociability ratio deficit discrimination learning increased amphetamineinduced hyperlocomotion cfos expression mice beta2 deletion colocalization analysis showed increased cfos expression present medium spiny neurons presumed striatal interneurons present study concludes despite relatively rare beta2containing nachrs primarily expressed striatal neurons cins play significant role behaviorsignificance statementa large variety nicotinic acetylcholine receptors expressed striatum brain region crucial control behavior complexity receptors different functions hindering understanding mechanisms striatal acetylcholine modulates behavior focused role small population beta2containing nicotinic acetylcholine receptors identified neuronal types expressing receptors determined impact control explorative behavior anxietylike behavior learning sensitivity stimulants additional experiments showed alterations associated overall increased activity striatal neurons thus small population nicotinic receptors represents interesting target modulation response stimulant drugs striatalbased behavior,0.0
pattern classification hand movement tremor ms patients dbs j biomed phys eng 2022 feb 1 12 1 2130 doi 1031661 jbpev0i01028 ecollection 2022 febabstractbackground hand tremor one consequences ms disease degrading quality patients life recently dbs used prominent treatment reduce effect evaluation approach significant importance prevalence rate diseaseobjective purpose study nonlinear analysis tremor signal order evaluate quantitative effect dbs reducing ms tremor differentiating using pattern recognition algorithmsmaterial methods analytical study nine features extracted tremor signal statistical analysis significance level feature examined finally tremor signals categorized svm weighted knn nn classifiers performance methods compared roc graphresults results demonstrated dominant frequency maximum amplitude energy first imf deviation direct path sample entropy fuzzy entropy potential create significant difference tremor signals classification accuracy rate tremor signals three groups weighted knn nn svm gaussian quadratic kernels resulted 951 932 913 883 respectivelyconclusion generally nonlinear nonstationary analyses high potential quantitative objective measure ms tremor weighted knn shown best performance classification accuracy 95 indicated dbs positive influence reducing ms tremor therefore dbs can used objective improvement tremor ms patientspmid35155289 pmcpmc8819264 doi1031661 jbpev0i01028,0.0
evaluation il1beta il6 expression following ebna1 brlf1 peptide treatment epstein barr viruspositive multiple sclerosis patients intervirology 2022 feb 14 doi 101159 000522577 online ahead printabstractintroduction epsteinbarr virus ebv hhv4 implicated pathogenesis multiple sclerosis ms study conducted investigate levels proinflammatory cytokines il1 il6 healthy epsteinbarr virus ebv carriers ms patients prior ebv infection response treatment epsteinbarr virus nuclear antigen 1 ebna1 replication transcription activator brlf1 rta peptide antigens whole blood cell culture assess cytokine expression across cells peripheral bloodmethods isolated whole blood cells included participants incubated concertation 106 cells ml brlf1 ebna1 amount il1 il6 transcripts measured quantitative rtpcr day 3 incubation mtt assay conducted examine cytotoxicity peptides effect cell viability changes cytokine expression cell viability analyzed using oneway twoway anova respectivelyresults ten ms patients ten healthy donors enrolled study treatment peptide antigens resulted increased cytokines expression ms patients healthy subjects furthermore il1 levels higher ms patients compared healthy ebv carriers mtt assay revealed significant difference cell viability two groupsdiscussion higher levels il1 response ebv antigens ms patients may reflect host neuroinflammatory environment support notion immune response ebv role aggravating factor progression ms contributing neuroinflammatory cascadepmid35158367 doi101159 000522577,0.0
secukinumab treatment psoriatic arthritis ankylosing spondyloarthritis multiple sclerosis case series literature review immunotherapy 2022 feb 14 doi 102217 imt20210128 online ahead printabstractbackground aim multiple sclerosis ms demyelinating central nervous system disorder cases reported concomitant spondyloarthritis spa spectrum disorders ankylosing spondylitis psoriatic arthritis aim study evaluate effectiveness secukinumab treatment ms accompanying ankylosing spondylitis psoriatic arthritis materials methods addition four cases authors conducted systematic literature search demographics comorbidities symptoms ms spa medical treatments changes clinical laboratory findings treatment recorded results conclusions secukinumab therapy patients found treatment response regarding axial involvement without progression ms observed spa spectrum diseases ms secukinumab may appropriate choicepmid35152720 doi102217 imt20210128,1.0
lowgrade oncocytic tumor lot new renal entity ready prime time updated review histol histopathol 2022 feb 1418435 doi 1014670 hh18435 online ahead printabstractlowgrade oncocytic tumor lot kidney recently proposed new renal entity lot identified spectrum oncocytic renal tumors overlapping features oncocytoma eosinophilic chromophobe renal cell carcinoma labelled one entities prior studies practice lot often single relatively small tumor found nonsyndromic setting rare examples multiple lots admixed tumors found patients tuberous sclerosis complex lot typically solid architecture composed eosinophilic cells round oval lowgrade nuclei lacking irregularities showing focal perinuclear halos sharp transition edematous stromal areas scattered loosely arranged cells frequently found lot consistent immunohistochemical profile diffuse reactivity cytokeratin 7 absent rarely weak expression cd117 profile different oncocytoma eosinophilic chromophobe renal cell carcinoma similarly contrast entities also lacks shows weak expression foxi1 recent studies shown lot molecular genetic profile different renal tumors frequent alterations affecting mtor tsc pathway genes lot demonstrates either disomic pattern deletions 19p13 19q13 1p36 lacks complete chromosomal losses gains published studies date lot shown benign behavior review summarize evidence recently published studies strongly supports conclusion lot distinct unique renal entitypmid35156688 doi1014670 hh18435,0.0
generating realworld data health records design patientcentric study multiple sclerosis using commercial health records platform jamia open 2022 jan 17 5 1 ooab110 doi 101093 jamiaopen ooab110 ecollection 2022 aprabstractobjective flywheelms study will explore use realworld health record data set generated picnichealth patientcentric health records platform improve understanding disease course patterns care patients multiple sclerosis ms materials methods flywheelms study aims enroll 5000 adults ms united states create large deidentified longitudinal data set clinical research picnichealth obtains health records including paper charts electronic health records radiology imaging files healthcare site using largescale health record processing pipeline picnichealth abstracts standard conditionspecific data elements structured eg laboratory test results unstructured eg narrative text maps standardized medical vocabularies researchers can use resulting data set answer empirical questions study participants can access share harmonized health records using picnichealths web applicationresults november 24 2020 4176 participants 49 50 us states enrolled flywheelms study median 200 pages records collected 14 different doctors 8 years per participant abstraction precision established interabstractor agreement high 978 identifying mapping data elements standard ontologyconclusion using commercial health records platform flywheelms study generating realworld multimodal data set provide valuable insights patients ms approach data collection abstraction diseaseagnostic used address clinical research questions futurepmid35155999 pmcpmc8827034 doi101093 jamiaopen ooab110,0.0
walking horizontal head turns impaired persons earlystage multiple sclerosis showing normal locomotion front neurol 2022 jan 28 12821640 doi 103389 fneur2021821640 ecollection 2021abstractbackground turning head walking action often required daily living particularly challenging maintain balance can therefore potentially reveal subtle impairments earlystage people multiple sclerosis still show normal locomotion nwpwms help identifying subjects can benefit early preventive exercise aimed slowing msrelated functional declineobjectives analyze assessment walking horizontal head turns whht inertial sensors can discriminate healthy subjects hs nwpwms nwpwms subgroups assess discriminant ability instrumented whht higher compared clinical scores assess concurrent validity sensorbased metricsmethods multicenter study 40 hs 59 nwpwms expanded disability status scale edss 25 disease duration 5 years tested participants executed item6 fullerton advanced balance scaleshort fabs wearing three inertial sensors trunk ankles item required horizontally turn head beat metronome 100 bpm walking signals sensors processed compute spatiotemporal regularity symmetry dynamic stability trunk sway metrics descriptive whhtresults mediolateral regularity anteroposterior symmetry mediolateral stability reduced nwpwms vs hs p 0001 showed moderate discriminant ability area receiver operator characteristic curve auc 071073 ap symmetry ml stability reduced p 0026 edss 225 vs edss 015 subgroup auc 069070 number nwpwms showing least one abnormal instrumented metric 68 larger p 0002 number participants showing abnormal fabsitem6 32 fabs clinical scores 39 edss 225 subgroup included individuals showing abnormal instrumented metrics 86 compared edss 015 subgroup 57 instrumented metrics significantly correlated fabsitem6 fabs scores spearmans r s 037 p 0001 thus demonstrating concurrent validityconclusion instrumented assessment whht provided valid objective metrics discriminated higher sensitivity clinical scores hs nwpwms edss subgroups method promising tool complement clinical evaluation reveal subclinical impairments persons can benefit early preventive rehabilitative interventionspmid35153994 pmcpmc8833075 doi103389 fneur2021821640,0.0
local cholesterol metabolism orchestrates remyelination trends neurosci 2022 feb 10s01662236 22 000133 doi 101016 jtins202201001 online ahead printabstractcholesterol essential component cell membranes particularly enriched myelin membranes myelin membranes major target immune attacks chronic neurological disorder multiple sclerosis ms demyelinating insults cholesterol released damaged myelin increasing local levels unique lipid impeding tissue regeneration summarize current knowledge cholesteroldependent processes demyelination remyelination emphasizing cell typespecific responses discuss cellular lipid cholesterol metabolism early late disease phases highlight concept lipidbased pharmacological interventions propose knowledge interplay cell typespecific cholesterol handling inflammation bloodbrain barrier bbb integrity will unravel disease processes facilitate development strategies therapies promote remyelinationpmid35153084 doi101016 jtins202201001,1.0
evaluating effects epigallocatechin3gallate hif1alpha protein rorc gene expression peripheral blood mononuclear cells patients multiple sclerosis basic clin neurosci 2021 julaug 12 4 533540 doi 1032598 bcn202122521 epub 2021 jul 1abstractintroduction multiple sclerosis ms chronic inflammation central nervous system cns autoimmune disease ms widely considered mediated activation myelinspecific t cd4+ cells well th1 th17 cells th17 cells involved pathogenesis ms various manners hif1 rorc required natural differentiation th17 essential transcription factors evolution th17 cells numerous studies indicated epigallocatechin gallate egcg presents immunomodulatory antiinflammatory effects study investigated effects egcg normoxic hif1 rorc2 expression pbmcs among ms patientsmethods peripheral blood mononuclear cells pbmcs isolated whole blood new cases ms cells cultured presence different concentration egcg 25 50 100m 18 48 hours next hif1 rorc2 level expressions measured enzymelinked immunosorbent assay elisa realtime pcr respectivelyresults results showed egcg significantly decreased rorc2 gene expression egcg affect level hif1conclusion however egcg influence level hif1 present data led us conclude egcg considered antiinflammatory agent may serve achievable therapeutic agent mspmid35154593 pmcpmc8817175 doi1032598 bcn202122521,1.0
lipoxins nervous system brighter prospects neuroprotection front pharmacol 2022 jan 26 13781889 doi 103389 fphar2022781889 ecollection 2022abstractlipoxins lxs generated arachidonic acid involved resolution inflammation confer protection variety pathological processes nervous system lxs exert array protective effects neurological diseases including ischemic hemorrhagic stroke neonatal hypoxiaischemia encephalopathy brain spinal cord injury alzheimers disease multiple sclerosis neuropathic pain lipoxin administration potential therapeutic strategy neurological diseases due notable efficiency unique superiority regarding safety provide overview lxs terms synthesis signaling pathways neuroprotective evidence overall believe along advances lipoxinrelated drug design lxs will bring brighter prospects neuroprotectionpmid35153778 pmcpmc8826722 doi103389 fphar2022781889,1.0
role lowlevel laser therapy treatment multiple sclerosis review study j lasers med sci 2021 dec 28 12e88 doi 1034172 jlms202188 ecollection 2021abstractintroduction multiple sclerosis ms autoimmune disease inflammatory cells cytokines chemokines play major role pathogenesis disease lowlevel laser therapy lllt photobiostimulation approach affect wide range cellular responses lllt inhibits inflammatory signaling pathway improves cell viability inhibits apoptosis modulates immune responses induces production growth factors methods review discuss effect lllt cellular responses application treatment ms keywords lowlevel laser therapy photobiomodulation multiple sclerosis used find studies related laser therapy ms google scholar pubmed medline databases results lllt reduced inflammatory immune cells mediators also enhanced regeneration neurons conclusion investigations showed besides current treatment strategies lllt promising therapeutic approach treatment mspmid35155173 pmcpmc8837843 doi1034172 jlms202188,0.0
microrna22 novel potent biological therapeutics neurological disorders mol neurobiol 2022 feb 14 doi 101007 s12035022027698 online ahead printabstractmicrornas mirs regulatory rnas 1825 nucleotides lengths involved various biological processes mirs including mir22 play essential role regulating neurological disorders mir22 brainenriched regulatory element involved angiogenesis energy supply adjustment ionic channels suppression malignant cell proliferation migration invasion article discusses protective therapeutic effects mir22 neurological diseases injuries including cerebral ischemia neurodegenerative diseases epilepsy brain malignancies also correlated mir22 amyotrophic lateral sclerosis als multiple sclerosis ms panic disorders schizophrenia neural tube defect anencephaly traumatic brain injury work provides therapeutic perspective mir22 new approach treating neurological disorderspmid35156160 doi101007 s12035022027698,0.0
analysis factors correlated spinal clinically isolated syndrome conversion multiple sclerosis neurol neurochir pol 2022 feb 14 doi 105603 pjnnsa20220016 online ahead printabstractintroduction present study aims explore factors influencing spinal clinically isolated syndrome cis conversion multiple sclerosis ms material methods sixtyone patients diagnosed spinal cis january 2010 november 2020 divided nonprogressing cis group 27 patients conversion ms ms group 34 patients based whether converted ms clinical presentation onset expanded disability status scale edss steroid therapy results magnetic resonance imaging mri oligoclonal bands cerebrospinal fluid csfocb evoked potentials eps retrospectively analysedresults differences gender age statistically significant ms cis groups median time relapse 12 months ms group upper quartile 237 months 912 patients relapsed within three years univariate analysis patients cis beginning sensory symptoms lower level progression ms 0311 patients kurtzke functional systems scores fsss pyramidal functions 2 3582 positive csfocb 5208 quickly progressed ms significant difference two groups terms spinal cord lesions 3 vertebral segments gadolinium enhancing lesions abnormal eps difference edss scores steroid therapy higher ms group cis group p 0001 differences 15 edss scores steroid therapy risk factors cis conversion ms 9333 conclusions patients spinal cis pure sensory abnormalities onset less likely convert ms 0311 risk factors order risk difference edss score steroid therapy 15 9333 positive csfocb 5208 fss pyramidal functions score 2 3582 present study serves simple first step potential predictors identified validated via future prospective studiespmid35156691 doi105603 pjnnsa20220016,0.0
neurobiological promises bitter diterpene lactone andrographolide oxid med cell longev 2022 feb 1 20223079577 doi 101155 2022 3079577 ecollection 2022abstractandrographolide andro bitter diterpene lactone found andrographis paniculata burmf nees possesses several biological effects antioxidant antiinflammatory organoprotective effects scientific reports suggest also neuroprotective capacity various test systems purpose review synthesize neuropharmacological properties andro highlight molecular mechanisms action highlight activities careful search done pubmed google scholar databases using specific keywords findings suggest andro possess neuroprotective analgesic antifatigue effects prominent effects stated neuroinflammation cerebral ischemia alzheimers parkinsons diseases multiple sclerosis brain cancer mice rats furthermore andro derivatives can enhance memory learning capacity experimental animals rats without causing toxicity brain thus andro may one promising plantbased psychopharmacological lead compounds new drug developmentpmid35154564 pmcpmc8825670 doi101155 2022 3079577,1.0
efficacy bvitamins vitamin d therapy improving depressive anxiety disorders systematic review randomized controlled trials nutr neurosci 2022 feb 14121 doi 101080 1028415x20222031494 online ahead printabstractobjectives systematic review aimed evaluate efficacy b vitamins vitamin d therapy improving standard treatment depression anxiety disorders also aimed gather evidence supporting recommendations supplementation clinical practicemethods performed march 2020 september 2021 main inclusion criteria randomized controlled trials rcts patients 18 years old sexes fulfilling target diagnoses major depressive disorder mdd generalized anxiety disorder gad mild severe depressive anxiety symptoms addition rcts included scales assess severity symptoms standardized rating scales psychiatric trials reported diagnoses schizophrenia perinatal depression bipolar depression sleep disorders eating disorders cancer multiple sclerosis association mentioned diagnoses excludedresults identified 20 rcts matched eligibility criteria totaling 2 256 subjects diagnosed mdd gad depressive anxiety symptoms supplementation folic acid lmethylfolate b1 b12 methylcobalamin vitamin d different doses study duration significantly decreased depression anxiety score scales increasing response standard pharmacological treatment monotherapy including partial complete remissiondiscussion b vitamins vitamin d associated compounds also showed significant results improvement symptoms attributed strictly results suggest intervention b vitamins vitamin d may effective welltolerated adjuvant strategy improving symptoms depression anxiety according patients clinical status nutritional biomarkerspmid35156551 doi101080 1028415x20222031494,0.0
role immunometabolism pathogenesis systemic lupus erythematosus front immunol 2022 jan 26 12806560 doi 103389 fimmu2021806560 ecollection 2021abstractsystemic lupus erythematosus sle chronic autoimmune disorder pathogenic abnormalities within innate adaptive immune response described order activated proliferate maintain immunological response drastic upregulation energy metabolism required recently greater understanding changes cellular bioenergetics provided new insight links immune response pathogenesis number diseases ranging cancer diabetes multiple sclerosis review highlight latest understanding role immunometabolism sle particular focus role abnormal mitochondrial function lipid metabolism mtor signaling immunological phenomenon observed sle also consider implications future therapeutic options management disease futurepmid35154082 pmcpmc8826250 doi103389 fimmu2021806560,0.0
primary antiphospholipid syndrome pediatrics beyond thrombosis report 32 cases review evidence abstractobjectivedescribe frequency thrombotic nonthrombotic clinical manifestations laboratory treatment prognosis patients pediatric primary antiphospholipid syndromematerial methodsa retrospective study carried patients diagnosis primary antiphospholipid antibody syndrome 16 years age followup pediatric rheumatology service general hospital national medical center la raza january 2013 december 2020 antiphospholipid syndrome defined met laboratory criteria sidney criteria presence thrombosis noncriteria manifestations disease hematological neurological cutaneous renal cardiac pulmonary demographic clinical laboratory treatment prognosis data collectedresultswe report 32 patients 21 female 65 11 male 35 mean age 1175 years evolution time 16 weeks thrombosis 9 patients 28 1 arterial 8 venous nonthrombotic manifestations hematologic thrombocytopenia 22 patients 69 autoimmune hemolytic anemia 13 40 fisherevans syndrome 6 19 lupus anticoagulant hypoprothrombinemia syndrome 2 6 dermatological livedo reticularis 20 62 skin ulcers 2 6 raynauds phenomenon 8 25 neurological epilepsy 1 3 migraine 3 9 chorea 1 3 cognitive impairment 3 9 renal 4 13 laboratory prolonged aptt 30 93 lupus anticoagulant 32 100 positive igg anticardiolipin 20 62 positive igm anticardiolipin 19 60 antib2gpi performed 3 patients positive treatment anticoagulation patients thrombosis antiplatelet 23 72 steroid 30 94 immunosuppressant 30 94 rituximab 4 125 deaths reportedconclusionsthe clinical characteristics patients pediatric primary antiphospholipid syndrome differ presented adults since nonthrombotic manifestations frequent children classification criteria include manifestations necessary better characterization disease pediatric population,0.0
got catch baby qualitative study hospital birth background 16 planned births united states occur hospitals studies indicate planned outofhospital birth oohb safe satisfying women however great variation among ethnic groups black women underrepresented recent phenomenon choice unassisted birth uab midwife professional maternity care attendant purpose study fill gap understanding reasons choosing oohb uab two clinically important subgroups women black women women experienced childhood physical sexual abusemethodsthis study recruited 18 women oohb uab identified either black survivors trauma participate indepth qualitative interviews concerning choice give birth hospital grounded theory approach utilized involved discursive process data collection coding textual passages identify focused themes memo writing document analytic decisionmaking eventual conceptual modelingresultsall 18 participants endorsed history trauma focused coding identify inherent concepts led emergence theoretical model arc decisionmaking around choice place birth birth attendant lack thereof women may choose oohb uab previous trauma feel discriminated healthcare professionals either skin color age pregnancy weight health condition women may choose oohb uab affords control process giving birthconclusionprevious trauma experiences discrimination influential factors women study sample choice birthplace setting choice provider findings can inform clinical understanding birth professionals including doctors midwives doulas nurses social workers psychologists contributes broadly national conversation birth choices usa,0.0
cognitive function pediatriconset relapsing myelin oligodendrocyte glycoprotein antibodyassociated disease mogad abstractintroduction myelin oligodendrocyte glycoprotein antibodies identified approximately 3050 youth pediatriconset acquired demyelinating syndromes little known cognitive sequelae relapsing myelin oligodendrocyte glycoprotein antibodyassociated disease mogad onset childhood adolescenceoverall adults 41 risk children relapse whole disease course overall adults 41 risk children relapse whole disease courseobjective compare cognitive performance participants pediatriconset relapsing mogad pediatriconset multiple sclerosis poms agematched healthy controlsmethods penn computerized neurocognitive battery pcnb administered 12 individuals relapsing mogad age16348 years 75 female disease duration8127 years 68 individuals poms age18340 years 72 female disease duration3839 years 108 healthy controls age17049 years 685 female accuracy assessed four domains executive function episodic memory complex cognition social cognition overall response time rt rt across three factors ie time constrained openwindow memory global performance determined composite score multiple linear regression used examine group differences pcnb domain factor zscores controlling age sex also covaried disease duration relapsing mogad vs poms analysesresults relative healthy controls relapsing mogad participants less accurate complex cognition domain b028 se011 p02 slower overall response time b016 se007 p02 relative poms relapsing mogad participants accurate executive function domain b070 se030 p02 battery overall b041 se018 p02 relative controls overall pcnb score significantly lower poms group b028 se006 p001 whereas relapsing mogad participants differ controls p06 overall pcnb scoreconclusions relapsing mogad group demonstrated reduced reasoning skills slower overall response time relative controls broad pattern deficits observed among poms participants relative controls overall cognitive difficulties mogad group milder relative poms group,1.0
sick sinus syndrome initial manifestation neuromyelitis optica spectrum disorder case report background sick sinus syndrome sss known occur due lesions medulla oblongata although medullary lesions occurred patients neuromyelitis optica spectrum disorder nmosd reports sss associated nmosd report patient nmosd developed refractory nausea vomiting sss initial manifestationcase presentationa 77yearold female developed refractory nausea frequent episodes syncope patient diagnosed sss sinus pauses lasting five six seconds observed pacemaker implantation performed two months later referred hospital limb weakness sensory impairment progressed month patient confirmed muscle weakness manual muscle testing revealed grade 4 upper extremities grade 3 lower extremities tendon reflexes diminished pathological reflexes present thermal pain sensations impaired upper lower extremities vibration sensation impaired lower extremities bladder rectal disturbances also noted optic neuritis detected t2weighted magnetic resonance imaging mri showed highintensity lesions dorsal part medulla oblongata c36 cervical cord serum positive antibodies aquaporin 4 diagnosis nmosd made treated two courses intravenous methylprednisolone pulse one course plasma exchange transferred another hospital rehabilitationconclusionsbecause sss lifethreatening complication clinicians aware possibility medullary lesions nmosd can cause sss initial manifestation,0.0
proximity proteomics c9orf72 dipeptide repeat proteins identifies molecular chaperones modifiers polyga aggregation abstractthe common inherited cause two genetically clinicopathologically overlapping neurodegenerative diseases amyotrophic lateral sclerosis als frontotemporal dementia ftd presence expanded ggggcc intronic hexanucleotide repeats c9orf72 gene aside haploinsufficiency toxic rna foci another nonexclusive disease mechanism noncanonical translation repeat rna five different dipeptide repeat proteins dprs form neuronal inclusions affected patient brains evidence cellular animal models supports toxic gainoffunction pathologic polyga polygr polypr aggregates promoting deposition tdp43 pathology neurodegeneration affected brain areas relative contribution dprs disease process c9ftd als patients remains unclear used proximitydependent biotin identification bioid proximity proteomics approach investigate formation collective composition dpr aggregates using cellular models interactomes arginine rich polygr polypr aggregates overlapped enriched nucleolar ribosomal proteins polyga aggregates demonstrated distinct association proteasomal components molecular chaperones hspa1a hsp70 hspa8 hsc70 vcp p97 cochaperones bag3 dnaja1a factors regulate protein folding degradation sqstm1 p62 calr chip stub1 experiments cellular models polyga pathology show molecular chaperones cochaperones sequestered periphery dense cytoplasmic aggregates causing depletion typical cellular localization involvement pathologic process confirmed autopsy brain tissue hspa8 bag3 vcp adapter protein ubxn6 show close association polyga aggregates frontal cortex temporal cortex hippocampus c9ftld c9als cases association heat shock proteins cochaperones polyga led us investigate potential role reducing aggregation identified hsp40 cochaperones dnajb family potent modifiers increased solubility polyga highlighting possible novel therapeutic avenue central role molecular chaperones pathogenesis human c9orf72linked diseases,0.0
multifactorial interdisciplinary intervention prevent functional mobility decline participation pre frail communitydwelling older adults prometheus study protocol multicenter randomized controlled trial background agerelated decline physical capacity can lead frailty associated increased vulnerability adverse health outcomes greater healthcare utilization aging population effective strategies prevent physical decline frailty preserve independence needed prevention programs vulnerable communitydwelling older adults however often yet established implemented routine practice research feasibility implementation cost effectiveness multifactorial interdisciplinary intervention programs take advantage available services healthcare providers also limited main aim study evaluate effectiveness intervention program prometheus prevent functional mobility decline participation communitydwelling pre frail older adultsmethodsthe study designed threecenter randomized controlled trial 12month intervention period four hundred communitydwelling pre frail clinical frailty scale score 46 older adults 70 years will randomized 11 ratio intervention group ig control group cg ig will receive prometheus program consisting obligatory homebased physical exercises weightbearing exercise better balance accompanied physiotherapists facultative counseling services personenvironmentfit coping everyday life nutrition groupbased activities delivered via existing healthcare structures eg social workers nutritionists cg will receive usual care onetime counseling session recommendations physical activity nutrition primary outcomes assessed months 6 12 function component latelife function disability instrument university alabama birmingham lifespace assessment secondary outcomes disability physical capacity activity frailty nutritional status falls fear falling health status psychosocial components process economic evaluations also conducted primary statistical analyses will based intentiontotreat principlediscussioncompared usual care prometheus program expected result higher function mobility greater independence lower need care participation prometheus program draws existing german healthcare structures largescale translation delivery will feasible evidence cost effectiveness successful implementation can demonstratedtrial registrationgerman clinical trials register registered march 11 2021,0.0
spontaneous remyelination lesions protects integrity surrounding tissues time multiple sclerosis eur j neurol 2022 feb 12 doi 101111 ene15285 online ahead printabstractbackground lesion remyelination preserves axonal integrity animal models multiple sclerosis ms invivo demonstration protective effect surrounding tissues humans lackingmethods nineteen persons ms enrolled cohort study underwent 2 pet mri scans 14 months apart voxelwise maps 11 c pib distribution volume ratio reflecting myelin content used calculate index baseline demyelination dynamic demyelination remyelination followup 549 single white matter lesions changes fractional anisotropy fa mean diffusivity md reflecting microstructural damage calculated proximal distal 3mmthick rings surrounding lesion used classify perilesional microstructure preserved worsening followup mixedeffect linear models logistic regressions employed investigate whether petderived lesional indices associated changes mri metrics perilesions identify best predicted microstructural evolution perilesions timeresults higher index remyelination lower index baseline dynamic demyelination lesions associated less severe microstructural deterioration corresponding proximal distal perilesions time pvalue range00010012 index remyelination best predicting variable perilesional fate every extra 1 remyelination within lesion probability corresponding perilesional microstructure remain preserved time increased 39 or662 95ci2162032 p0001 conclusions intralesional remyelination associated microstructural preservation surrounding tissues possibly preventing neuroaxonal damage resulting wallerian degenerationpmid35152511 doi101111 ene15285,1.0
nutritional status patients advancedstage multiple sclerosis eur j neurol 2022 feb 12 doi 101111 ene15286 online ahead printabstractintroduction motor swallowing dysfunctions multiple sclerosis ms unbalance calories intakes energy expenditure modifying nutritional status ns one study described ns ms patients early stages median edss 3 never assessed severe goal present study describe ns advancedstage msmethods study noninterventional retrospective analysis prospective registry reviewed medical files consecutive ms patients admitted annual followup physical rehabilitation medicine unit may 2016 october 2018 malnutrition frail people according french health authority definition composite primary outcome criterion body mass index bmi 21kg m2 albumin35g l first performed descriptive analysis nutritional status second studied association malnutrition ms characteristics univariate multivariate analysesresults 163 patients median edss8 7 85 included ninetythree patients 57 met malnutrition criterion 36 albumin35g l 31 bmi21kg m2 10 malnutrition associated univariate analysis ms severity edss85 p00003 primary progressive type ms p001 swallowing disorders p0002 multivariate analysis showed low disability status edss 7 independent protective factor associated malnutrition 02 p003 conclusion malnutrition frequent advanced stages ms probably key point therapeutics never demonstrated standardized evaluation developed improve nutritional therapeutic strategies populationpmid35152502 doi101111 ene15286,0.0
salivary biomarkers neurodegenerative demyelinating diseases biosensors detection ageing res rev 2022 feb 10101587 doi 101016 jarr2022101587 online ahead printabstractsalivary analysis gaining increasing interest novel promising field research diagnosis neurodegenerative demyelinating diseases related aging collection saliva offers several advantages noninvasive stressfree repeatable moreover detection biomarkers directly saliva allow early diagnosis disease leading timely treatments aim manuscript highlight relevant researchers findings relatively salivary biomarkers neurodegenerative demyelinating diseases describe innovative advanced biosensing strategies detection salivary biomarkers review focused five relevant agingrelated neurodegenerative disorders alzheimers disease parkinsons disease amyotrophic lateral sclerosis huntingtons disease multiple sclerosis salivary biomarkers commonly associated advanced biosensors enabling molecular diagnostics detection salivary biomarkers presented order stimulate future research direction pave way clinical applicationpmid35151849 doi101016 jarr2022101587,1.0
amino acid solute carrier transporters inflammation autoimmunity drug metab dispos 2022 feb 12dmdar2021000705 doi 101124 dmd121000705 online ahead printabstractthe past decade exposed importance many homeostasis metabolism related proteins autoimmunity disease inflammation solute carriers slcs group membrane channels can transport amino acids building blocks proteins nutrients neurotransmitters review summarizes role slcs amino acid transporters inflammation autoimmunity disease detail importance glutamate transporters slc1a1 slc1a2 slc1a3 mainly expressed brain help prevent glutamate excitotoxicity discussed context central nervous system disorders multiple sclerosis similarly cationic amino acid transporter slc7a1 cat1 important arginine transporter t cells slc7a2 cat2 essential innate immunity slc3 family proteins bind light chains slc7 family slc7a5 slc7a7 slc7a11 form heteromeric amino acid transporters also explored describe roles t cells nk cells macrophages tumor immunotherapies altogether link slc amino acid transporters inflammation autoimmunity may contribute better understanding underlying mechanism disease provide novel potential therapeutic avenues significance statement significance statement review summarize link slc amino acid transporters inflammation immune responses specially slc1 family members slc7 members studying link may contribute better understanding related diseases provide potential therapeutic targets useful researchers interest involvement amino acids immunitypmid35152203 doi101124 dmd121000705,0.0
cumulative incidence predictors acquired aortic stenosis large population men followed 43years background acquired aortic stenosis increases age high mortality without intervention factors predicting development unclear although atherosclerotic factors assumed involved aim study estimate lifetime cumulative incidence predictors middleaged menmethodswe included random sample men n 9998 born 19151925 gothenburg sweden 7 494 examined followed diagnosis death maximum followup time 428 years identified diagnosis swedish national patient registry deaths swedish cause death registry using international classification disease icd diagnostic criteria study timedependent relationships risk factors death competing risk divided cohort three overlapping followup groups 2543 3043 3543 years used ageadjusted cox proportional hazards model identify predictors asresultsthe lifelong cumulative incidence 32 baseline participants third group healthier lifestyle lower body mass index bmi blood pressure serum cholesterol levels higher bmi obesity cholesterol hypertension atrial fibrillation smoking heredity stroke associated bmi 20225 reference hazard ratios diagnosed men baseline bmi 25275 kg m2 27530 kg m2 30 kg m2 199 95 ci 112355 298 95 ci 165540 355 95 ci 184687 respectivelyconclusionsthe lifetime cumulative incidence middleaged male population 32 multiple atherosclerotic risk factors particularly high bmi might associated higher risk developing,0.0
epidemiology multiple sclerosis west bank palestine abstractbackgroundmultiple sclerosis ms common demyelinating disease central nervous system major neurologic cause disability young adults incidence prevalence vary significantly different ethnic groups geographical regions thought ms frequent go equator palestine yet published data concerning incidence prevalence article aim study epidemiological clinical characteristics ms west bank palestinemethodsa retrospective observational study conducted year 2010 2019 among ms patients west bank demographic clinical records concerned patients collected database palestinian ministry health age sex onset symptoms first symptom year diagnosis family history smoking noted crude 2019 prevalence incidence rate calculatedresultswe identified 1652 ms patients 1074 6501 females 578 3499 males 2010 crude incidence rate 196 cases per 100 000 peaked 2017 608 dropped unexpectedly 2018 291 rerose 354 2019 incidence rates among females higher males 2010 2019 802 730 patients diagnosed age groups 30 year 3045 year respectively comprises 9274 patients males slightly affected later age group 3045 whereas females affected age group 30 common symptom disease onset motor presentation 1604 followed blurring vision 1574 conclusionthis first epidemiological study regarding ms disease west bank palestine results showed crude incidence rate increasing 2010 2017 part due increasing awareness disease well availability diagnostic tools researches will necessary closely monitor increasing trend disease amongst palestinian population coming future clinical features disease similar described literature,1.0
safety humoral response rate inactivated mrna vaccines sarscov2 patients multiple sclerosis abstractbackground safety effectiveness outcomes multiple sclerosis ms patients receiving different diseasemodifying therapies dmt different types vaccines sarscov2 limited growing evidence coming mainly israel europe north america using mrna adenoviral vector vaccines publishedobjectives assess safety humoral response inactivated virus mrna vaccines sarscov2 patients msmethods ongoing multicentric prospective observational study performed february september 2021 humoral response antibodies spike1 protein determined least 4 weeks complete schedule antisarscov2 vaccines categorical outcome positive negative total antibody titres recorded adverse events supposedly attributable vaccination aesav collectedresults 178 patients 68 women mean age 397112 years 123 received inactivated coronavacsinovac 51 mrna pfizerbiontech 4 adenoviral vector vaccines cansino n2 jonhsonjohnsonjannsen n1 oxfordastrazeneca n1 six patients history covid19 vaccination overall humoral response observed 669 626 inactivated vs 784 mrna p004 positive antis1antibodies observed 100 patients dmt n3 100 interferon glatirameracetate n11 100 teriflunomide dimethylfumarate n16 100 natalizumab n10 100 alemtuzumab n8 90 cladribine n10 88 fingolimod n17 43 patients receiving anticd20 n99 positive 38 inactivated vaccine vs 59 mrna vaccine p005 multivariate analysis including anticd20 patients predictors positive humoral response receiving mrna vaccine 811 179368 p0007 lower number total infusions 044 027074 p0002 frequent aesav local pain 14 4 22 patients experiencing mildmoderate relapses within 8 weeks first vaccination compared 11 relapses 62 within 8 weeks vaccination chisquared 341 p006 discussion higher humoral response rate observed using mrna compared inactivated vaccine patients using anticd20 significantly lower response rate patients using anticd20 fingolimod lower antibody titres ms patient cohort inactivated mrna vaccines sarscov2 appear safe increase relapse rate information may help guidelines including booster shots types vaccines selected populations,0.0
research landscape tuberous sclerosis complexassociated neuropsychiatric disorders tand comprehensive scoping review background tuberous sclerosis complex tsc associated neuropsychiatric disorders tand umbrella term behavioural psychiatric intellectual academic neuropsychological psychosocial manifestations tsc although tand affects 90 individuals tsc lifetime manifestations relatively underassessed undertreated underresearched performed comprehensive scoping review tand research date describe existing tand research landscape b identify knowledge gaps guide future tand researchmethodsthe study conducted accordance stages outlined within arksey omalley scoping review framework ten research questions relating study characteristics research design research content tand levels clusters examinedresultsof 2841 returned searches 230 articles published 1987 2020 included animal studies 30 case studies 47 cohort studies 153 half published since term tand coined 2012 118 230 51 cohort studies largely involved children adolescents 63 opposed older adults 16 studies represented across 341 individual research sites 45 countries majority usa 89 341 26 uk 50 341 15 48 research sites 14 within lowmiddle income countries lmics animal studies case studies relatively high high quality cohort studies showed significant variability 153 cohort studies 16 10 included interventions none nonpharmacological 13 employed remote methodologies eg telephone interviews online surveys tand clusters autism spectrum disorderlike cluster widely researched 138 230 60 scholastic cluster least 53 200 27 conclusionsdespite recent increase tand research studies represent participants across lifespan lmic research sites nonpharmacological interventions identified future priorities quality cohort studies requires improvement use standardised direct behavioural assessments may contribute human studies academic level particular warrants investigation remote technologies help address many tand knowledge gaps identified,0.0
erratum quot assessing diagnosis disclosure concealment multiple sclerosis building framework moving forwardquot mult scler 2022 feb 1113524585221079450 doi 101177 13524585221079450 online ahead printno abstractpmid35148657 doi101177 13524585221079450,0.0
cognitive aspects multiple sclerosis psychiatr danub 2021 dec 33 suppl 13 177182abstractbackground cognitive dysfunction appears course multiple sclerosis ms mild moderate cognitive impairment present 40 ms patients severe cognitive decline affects 50 patients progressive course disease common cognitive disorders ms include diminished information processing speed compromised word fluency complex attention deficit executive dysfunctionmethods mini review present reader common neuropsychological assessments evaluation cognition ms addressing question cognitive relapse source data presented review pubmed search recently published literature cognitive decline msresults patients cognitive relapse often fail meet diagnostic criteria classical relapse ms although cognitive decline relates poorly functional disability ms correlates well neuropsychological testing neuroimaging parameters diseaseconclusions cognitive decline might considered additional indicator ms activity therefore evaluated routinely irrespective clinical presentation brief cognitive assessment confirmed psychometric qualities might useful detection cognitive relapse ms patientpmid35150483,0.0
epidemiology pharmacological treatment multiple sclerosis croatia psychiatr danub 2021 dec 33 suppl 13 204208abstracttreatment multiple sclerosis dynamic field lately many new emerging treatment options study investigate use disease modifying therapies dmts multiple sclerosis croatia data dmt use provided agency medicinal products medical devices croatia halmed data 2005 2016 available consumption dmts ddd 1000 day increasing 9 annually average since 2005 period annual cost drugs increasing 146 annually average consumption ifnbeta 1a increasing much steeper rate ifnbeta 1b 2010 consumption glatiramer acetate negligible steep increase 2011 2014 steady rate consumption since recently several new dmts became available namely dimethyl fumarate teriflunomide fingolimod natalizumab became available 2010 consumption growing steadily consumption figures exceeded alemtuzumab new dmts readily available croatia countries however continuous increase number prescriptions along growing costs pharmacological treatment multiple sclerosis can expected become even pronounced following years due abundance new therapeutic options steadily becoming availablepmid35150487,0.0
acquired stuttering sole manifestation relapse multiple sclerosis secondary involvement left frontal aslant tract acta neurol belg 2022 feb 11 doi 101007 s13760022018953 online ahead printno abstractpmid35149981 doi101007 s13760022018953,0.0
genetics familial distribution multiple sclerosis review rev neurol paris 2022 feb 8s00353787 22 000017 doi 101016 jneurol202111009 online ahead printabstractpurpose review article reviews genetics multiple sclerosis ms well intrafamilial concordance clinical correlations different members family indeed significant findings made topics recent yearsrecent findings influence specific genes clinical radiological presentation ms described well preliminary findings field pharmacogenomics within familial forms ms correlations specific aspects disease described age onset clinical course siblingssummary genetic contribution risk developing ms now estimated 50 genes involved mainly located within major histocompatibility complex familial ms represents 126 ms cases risk depending degree genetic proximity index case furthermore familial cases seem different clinical presentation sporadic cases earlier worsening disability severe longterm disability clinical correlations different members family ms also described similar age onset siblings deep clinical radiological phenotyping warranted investigate ms disease severity concordance within familial cases mspmid35148907 doi101016 jneurol202111009,0.0
interferon acts directly tcells prolong allograft survival enhancing regulatory t cell induction foxp3 acetylation immunity 2022 feb 8s10747613 22 000401 doi 101016 jimmuni202201011 online ahead printabstracttype interferons ifns pleiotropic cytokines potent antiviral properties also promote protective t cell humoral immunity paradoxically type ifns including widely expressed ifn also immunosuppressive properties including promoting persistent viral infections treating tcelldriven remittingrelapsing multiple sclerosis although associative evidence suggests ifn mediates immunosuppressive effects impacting regulatory t treg cells mechanistic links remain elusive found ifn enhanced graft survival tregcelldependent murine transplant model genetic conditional deletion models revealed extended allograft survival treg cellmediated required ifn signaling t cells using silico computational model analysis human immune cells found ifn directly promoted treg cell induction via stat1 p300dependent foxp3 acetylation findings identify mechanistic connection immunosuppressive effects ifn treg cells therapeutic implications transplantation autoimmunity malignancypmid35148827 doi101016 jimmuni202201011,0.0
antineuronal nuclear antibody 3 autoimmunity targets dachshund homolog 1 ann neurol 2022 feb 12 doi 101002 ana26320 online ahead printabstractthe antigen specificity antineuronal nuclear antibodytype 3 anna3 igg unknown identified dachshundhomolog 1 dach1 anna3 autoantigen confirmed antigenspecific assays immunohistochemical colocalization immune absorption experiments patients median age 635 years range 4988 67 female neurological manifestations information available 30 patients included one neuropathy 12 cognitive difficulties 11 ataxia 8 dysautonomia 7 evidence neoplasm present 27 30 90 neuroendocrine lineage dach1igg rare represents novel proposed biomarker neurological autoimmunity cancer article protected copyright rights reservedpmid35150165 doi101002 ana26320,0.0
comparing natural history early late onset pediatric multiple sclerosis ann neurol 2022 feb 12 doi 101002 ana26322 online ahead printabstractobjectives describe compare disease course prognosis early ie disease onset age 11 years late ie disease onset age 11 years onset pediatric multiple sclerosismethods prospectivelycollected clinical information italian multiple sclerosis register 1993 pediatric multiple sclerosis patients 172 early onset analyzed cox models adjusted sex baseline expanded disability status scale score diseasemodifying treatments stratified diagnostic criteria adopted poser vs mcdonald used assess risk reaching irreversible expanded disability status scale scores 3 4 6 conversion secondary progressive phenotype early vs late onset pediatric patients prognostic factors also evaluatedresults greater proportion males isolated brainstem involvement longer time interval first second clinical episode observed early vs late onset pediatric patients compared late onset early onset pediatric patients took longer time disease onset convert secondary progressive phenotype reach disability milestones recovery first demyelinating event time first relapse annualized relapse rate first 3 years disease diseasemodifying treatments exposure independent predictors longterm disability early onset pediatric patients late onset pediatric patients isolated optic neuritis multifocal symptoms progressive course disease onset additional predictors longterm disabilityinterpretation findings point towards existence different natural history early vs late onset pediatric multiple sclerosis patients article protected copyright rights reservedpmid35150168 doi101002 ana26322,1.0
cognitive impairment markers optical neurodegeneration early multiple sclerosis neurol sci 2022 feb 12 doi 101007 s10072022059459 online ahead printabstractintroduction cognitive impairment retinal atrophy proposed two potential markers neurodegeneration multiple sclerosis ms aimed assessing relation peripapillary retinal nerve fiber layer prnfl macular ganglion cell layer mgcl atrophy cognitive performance early msmethods multicenter crosssectional study patients early ms clinically isolated syndrome relapsingremitting ms edss score 30 patients previous optic neuritis ocular diseases psychiatric illness recent relapse excluded patients underwent standardized optical coherence tomography oct neuropsychological evaluation validated tests ms patients cognitive impairment defined two cognitive tasks age educationadjusted normsresults recruited 52 patients early ms average age 37 years sd 105 average disease duration 369 years sd 23 median edss 10 iqr 05 sample 15 52 patients presented cognitive impairment regarding oct measurements 7 52 patients average prnfl 5th percentile 2 52 average mgcl 5th percentile average prnfl thickness comparable cognitively impaired cognitively preserved patients 1003 m vs 1031 m p 052 average mgcl thickness also similar values groups 505 m vs 53 m p 038 conclusions cognitive impairment frequent sample early ms however association reduced prnfl mgcl thickness found compared oct cognitive assessment provide earlier marker neurodegeneration mspmid35150351 doi101007 s10072022059459,0.0
efficacy speed processing training improving processing speed individuals multiple sclerosis randomized clinical trial j neurol 2022 feb 12 doi 101007 s00415022109809 online ahead printabstractobjective current study examines efficacy speed processing training sopt improve processing speed ps individuals multiple sclerosis ms outcomes included changes useful field view ufov neuropsychological evaluation npe methods doubleblind placebocontrolled randomized clinical trial included 84 participants clinically definite ms impaired ps 43 treatment group 41 placebo control group participants completed baseline npe repeat npe posttreatment treatment group randomized booster sessions contact longterm followup assessments completed 6 months treatmentresults significant effect sopt observed ufov large effect pattern comparison similar pattern results noted letter comparison albeit trend level treatment effect maintained 6 months later impact booster sessions significant correlations degree improvement ufov number levels completed within training task significant speed divided attention indicating completion levels training correlated greater benefitconclusion sopt effective treating ps deficits ms benefit documented ufov neuropsychological measure ps less benefit observed outcome measures became distinct cognitive demands treatment longterm maintenance observed number training levels completed within 10sessions exerted significant impact treatment benefit levels completed resulting greater benefitpmid35150301 doi101007 s00415022109809,0.0
neurophysiological outcomes following mesenchymal stem cell therapy multiple sclerosis clin neurophysiol 2022 jan 29 1366981 doi 101016 jclinph202201125 online ahead printabstractobjective report neurophysiological outcomes derived transcranial magnetic stimulation tms following autologous mesenchymal stem cells amscs therapy patients multiple sclerosis ms methods 20 adults confirmed ms recruited participate phase ii randomized control trial assess safety potential benefits amscs infusion week 0 patients randomly assigned receive either amscs n 9 placebo infusion n 11 week 24 placebo group received amscs infusion blind assessments performed weeks 0 24 48 outcomes consisted tms measures corticomotor excitability motor conduction along measures motor impairments disabilityresults postinfusion change detected measures corticomotor excitability measures intra interhemispheric inhibition latency motor evoked potentials central motor conduction time significantly prolonged changes motor conduction associated declines hand dexterity postinfusionconclusion clinical neurophysiological measures showed improvement following amscs therapy cohort ms patientssignificance although promising stem cell therapy remains elusive regarding benefits influencing disease activity ms patientspmid35149266 doi101016 jclinph202201125,0.0
effects relaxation techniques pain fatigue kinesiophobia multiple sclerosis patients 3arm randomized trial j neurosci nurs 2022 feb 10 doi 101097 jnn0000000000000620 online ahead printabstractbackground addition available medical treatment options multiple sclerosis ms patients may tend toward complementary integrative therapies relaxation techniques nonpharmacological sideeffectfree therapy option currently available alleviate symptoms many different chronic diseases aim study examine compare effects relaxation techniques pain fatigue kinesiophobia ms patients methods 3arm randomized controlled trial consisted 80 ms patients relaxation techniques progressive muscle relaxation benson relaxation technique applied 2 intervention groups third control group study lasted 12 weeks patient information form visual analog scale fatigue severity scale tampa scale kinesiophobia used data collection results statistically significant decrease pain fatigue kinesiophobia levels intervention groups compared control group p 05 progressive muscle relaxation effective benson relaxation technique p 05 conclusion relaxation techniques recommended management symptoms pain fatigue kinesiophobia can often cause disability ms patients side effects practical administrations exercises also promising rehabilitation process ms patientspmid35149625 doi101097 jnn0000000000000620,0.0
symptoms related gastrointestinal tract involvement low muscularity systemic sclerosis clin rheumatol 2022 feb 11 doi 101007 s10067022060595 online ahead printabstractintroduction objectives gastrointestinal tract git involvement frequently observed systemic sclerosis ssc may lead nutritional impairment aim study assess prevalence symptoms related git involvement analyze possible association gastrointestinal symptoms low muscularity ssc patientsmethods sixtynine consecutive patients 60 females median age 53 iqr 4363 body mass index bmi 232 iqr 209246 kg m2 diagnosis ssc admitted scleroderma unit enrolled clinical status anthropometric data bioelectrical impedance inbody 770 usa analysisassessed fatfree mass index ffmi recorded upon enrollment ucla questionnaire used quantify git involvement seven specific scalesresults mean ffmi 162 kg m2 iqr 152176 median ucla total score 053 iqr 019089 ffmi showed significant negative correlation ucla total score r 029 p 0016 ucla distention bloating r 035 p 001 16 patients 231 ffmi reduced ucla distention bloating significantly higher p 0039 ssc patients lower ffmi 175 iqr 075212 vs 075 iqr 025175 multiple linear regression model ffmi showed association ucla distention bloating beta coefficient 0315 95 ci beta coefficient 0591 0039 p 0026 bmi beta coefficient 0259 95 ci beta coefficient 0163 0355 p 0001 disease duration beta coefficient 0033 95 ci beta coefficient 0059 0007 p 0015 conclusions ssc low ffmi associated symptoms related git involvement particular distension bloating key points ffmi associated symptoms related git involvement low ffmi associated symptoms related ucla distention bloating malnutrition associated symptoms related git involvementpmid35149929 doi101007 s10067022060595,0.0
postzygotic de novo ncdn mutation identified sporadic ftld patient results neurochondrin haploinsufficiency altered fus granule dynamics abstractfrontotemporal dementia ftd heterogeneous clinical disorder characterized progressive abnormalities behavior executive functions personality language motricity neuropathological subtype ftd frontotemporal lobar degeneration ftld fet characterized protein aggregates consisting rnabinding protein fused sarcoma fus cause ftldfet well understood lack genetic evidence aid investigation mechanisms disease goal study identify genetic variants contributing ftldfet investigate effects fus pathology performed wholeexome sequencing 50yearold ftld patient ubiquitin fuspositive neuronal inclusions unaffected parents identified de novo postzygotic nonsense variant ncdn gene encoding neurochondrin ncdn nm_0142843c1206g p trp402 variant associated 31 reduction fulllength protein levels patients brain suggesting mutation leads ncdn haploinsufficiency examined effects ncdn haploinsufficiency fus found depleting primary cortical neurons ncdn causes reduction total number fuspositive cytoplasmic granules moreover found granules significantly larger highly enriched fus examined effects loss fus function ncdn neurons found depleting cells fus leads decrease ncdn protein mrna levels study identifies ncdn protein likely contributor ftldfet pathophysiology moreover provide evidence negative feedback loop toxicity ncdn fus loss ncdn alters fus cytoplasmic dynamics turn impact ncdn expression,0.0
muscle stem cell adaptations cellular environmental stress background lifelong regeneration skeletal muscle dependent rare population resident skeletal muscle stem cells also named satellite cells anatomical position outside myofibre underneath basal lamina muscle stem cells maintain prolonged quiescence activate myogenic programme cell cycle response injury expand population myogenic progenitors required regenerate muscle skeletal muscle regenerate absence muscle stem cellsmain bodythe notion lifelong regeneration muscle dependent rare nonredundant population stem cells seems contradictory accumulating evidence muscle stem cells activated multiple stress response pathways example muscle stem cell quiescence mediated part eif2 arm integrated stress response negative regulators mtorc1 two translational control pathways downregulate protein synthesis response stress muscle stem cells also activate pathways protect dna damage heat shock environmental stress review accumulating evidence muscle stem cells encounter stress prolonged quiescence activation stress response pathways classically described bimodal whereby threshold dictates cell survival versus cell death responses stress review evidence muscle stem cells additionally respond stress spontaneous activation fusion myofibresconclusionwe propose cellular stress test model whereby prolonged state quiescence microenvironment serve selective pressures maintain muscle stem cell fitness safeguard lifelong regeneration muscle fit muscle stem cells maintain robust stress responses permitted maintain muscle stem cell pool unfit muscle stem cells depleted pool first spontaneous activation case severe stress activating cell death senescence pathways,0.0
amyloid pet imaging dementias potential applications detecting quantifying early white matter damage abstractpurposepositron emission tomography pet amyloid tracers amypet allows quantification pathological amyloid deposition brain tissues including white matter wm evaluate amypet uptake wm lesions wml normalappearing wm nawm patients alzheimers disease ad nonad type dementiamethodsthirtythree cognitively impaired subjects underwent brain magnetic resonance imaging mri a142 determination cerebrospinal fluid csf amypet twentythree patients exhibiting concordant results csf analysis amypet cortical amyloid deposition recruited divided two groups amyloid positive a+ negative wml quantification brain volumes segmentation performed standardized uptake values ratios suvr calculated grey matter gm nawm wml amypet coregistered mri imagesresultsa+ compared showed higher wml load p 0049 alongside higher suvr brain tissues p 001 correlations csf levels wml nawm suvr found a+ csf levels directly correlated nawm suvr p 004 csf concentration predictor nawm suvr adj r2 091 p 004 a+ direct correlations identified wm gm suvr p 001 conclusionsour data provide evidence role amypet assessment microstructural wm injury nonad dementia whereas amypet seems less suitable assess wm damage ad patients due plausible amyloid accrual therein,0.0
relationship weather daily physical activity time spent home older adults germany actife study background need comprehensive evaluation associations varieties weather conditions time spent outofhome toh walking duration wd among older adults aim investigate extent various weather parameters temperature solar radiation sunshine duration humidity windspeed rain determine daily wd toh older adultsmethodsthe actife activity function older people ulm study prospective study participants aged 65 years older wore accelerometer kept movement diary three temporally separated waves 2009 2018 duration seven days per wave three weeks summary used weather data weather station near participants homes ageadjusted genderstratified generalized mixed models used predict wd toh 95 confidence interval ci within weather categories generalized additive models computed single predictions weather quartile boundaries cubic splines 95 pointwise confidence bands cb visualized continuous course weather valuesresultshigher temperatures solar radiation hours sunshine led increase wd toh higher precipitation humidities windspeeds led decrease women general higher wd toh times menconclusionsour data suggest weather parameters considerable influence pa toh future analyses interpretation pa data therefore account weather parameters,0.0
validation norma latina neuropsychological assessment battery individuals multiple sclerosis mexico abstractbackgroundbetween 5060 multiple sclerosis ms patients cognitive alterations several batteries assess cognitive impairments ms however exist latin americans objective study evaluate neuropsychological profile mexican people ms pwms assess utility norma latina new battery cognitive assessment latin america differentiating cognitive test performance pwms healthy controls hc methods100 pwms 100 hc mexico evaluated norma latina battery following analyses conducted 1 lowpercentiles participant calculated 2 area curve used determine whether battery discriminated pwms hc 3 four composite scores calculated studentnulls ttest used compare groups according domainsresultspwms obtained greater number impaired scores compared hcs principally executive function battery successfully discriminated pwms hcs strongest capacity discriminate executive functions weakest memoryconclusionestablishing validation neuropsychological battery mexican pwms will help accurately detect cognitive alterations will guide decisions professionals terms cognitive rehabilitation,0.0
centrallylocated transverse myelitis facilitate differentiation nmosd mogad ms abstractobjectives differentiating neuromyelitis optica spectrum disorder nmosd myelin oligodendrocyte glycoprotein antibodydisease mogad multiple sclerosis ms important since ms therapies might result progression relapse former diseases evidence long extending transverse myelitis letm magnetic resonance imaging mri one requirements make nmosd diagnosis however centrally located lesions spinal mri may bring higher sensitivity specificity nmosd mogad diagnosismethods aimed assess association nmosd diagnosis presence centrally located lesions disease onset reviewed 102 medical records isfahan ms clinic presented cervical cord lesions 17 ms 23 nmosd 6 mogad patients selected collected demographic clinical mri data patients clinical presentations cervical cord lesion disease onset characteristics lesion studiedresults association nmosd diagnosis presence centrally located lesion cltm p0001 presence letm p0001 intermediate high axial cord expansion p0001 cltm letm can also found mogad patients presence cltm sensitivity specificity 9565 6956 possessed higher sensitivity specificity nmo diagnosis letm presence sensitivity specificity 7826 4347 conclusion diagnostic criteria including centrality location expansion transverse myelitis lesions addition letm may accurate diagnosis nmosd mogad distinction ms,1.0
higher uric acid serum levels associated sarcopenia west china crosssectional study background sarcopenia decline muscle strength mass attributed aging pathogenesis sarcopenia may triggered oxidative stress uric acid ua strong antioxidant properties aim study investigate relationship ua sarcopenia communitydwelling adults west china using baseline data west china health aging trend wchat studydesigna crosssectional studymethods4236 adults aged 50 years older communities west china enrolled study applied asian working group sarcopenia awgs 2019 criteria define sarcopenia muscle mass measured using skeletal muscle index smi based bioimpedance analysis bia handgrip strength hgs gait speed gs recorded respectively different variables like anthropometry measures life styles chronic disease blood test collected general linear model done investigate relationship ua hgs gs smi adjusting age ethnic groups sleeping quality education level cognitive function smoking history drinking history adl score chronic diseaseresultsparticipants grouped according ua quartiles gender adjusting potential confounders negative association serum ua levels sarcopenia shown men women significant association serum ua levels hgs women shown inverted j shape besides positive association ua quartiles smi observed irrespective genderconclusionsour results showed higher uric acid levels significantly correlated higher muscle mass grip strength among chinese adults aged 50 higher ua serum levels might slow progression sarcopenia,0.0
managing neuropsychological impairment multiple sclerosis controlled study standardized metacognitive intervention matims abstractobjective multiple sclerosis ms inflammatory neurodegenerative disease central nervous system potential autoimmune origin frequently associated neuropsychiatric symptoms cognitive deficits well fatigue stress psychosocial burden present controlled multicenter trial investigated whether two specific neuropsychological interventions 1 metacognitive training matims 2 computerized working memory training brainstim combination matims applied addon therapies real life standard rehabilitation lead increased benefit selfperceived cognitive deficits primary outcome ms patients compared standard rehabmethods 288 adult persons three german rehab centers confirmed diagnosis ms sequentially allocated one three intervention groups 249 87 participants completed post assessment 187 63 online survey 12 months perceived cognitive deficits mood fatigue coping activity evaluated selfreports neuropsychological tests baseline 4 weeks postintervention selfreports additionally administered digitally three six twelve months baselineresults show differential effects primary outcome intervention groups control group p369 p934 immediately intervention show beneficial time effects three groups selfperceived cognitive deficits well outcomes reported effects however sustained 6 months followupconclusions findings show additional effect specific cognitive training cognitive deficit perception ms however findings indicate ms rehabilitation may improve patient reported outcomes short term also underline need concepts maintain rehabilitation gains patients return back home,0.0
acute disseminated encephalomyelitis bilateral optic neuritis following chadox1 covid19 vaccination background acute disseminated encephalomyelitis adem rare immunemediated inflammatory demyelinating disease central nervous system report case adem presenting bilateral optic neuritis temporally associated chadox1 vaccine sarscovid19 viruscase presentationa 36yearold female presented bilateral optic neuritis following first dose chadox1 vaccine initial mri brain showed evidence demyelination within subcortical white matter radiological involvement optic nerves visual evoked potentials consistent bilateral optic neuritis confirmed radiologically follow mri treated intravenous steroids improvement symptoms radiological appearance pseudorelapse occurred treated course intravenous steroids followed oral taper clinical radiological serological results consistent diagnosis ademconclusionsadem exceedingly rare complication chadox1 vaccine despite millions doses imperative clinicians remain aware neurological complications vaccines importance vaccination control pandemic undermined,1.0
comparative importance mental physical disorders healthrelated days role general population saudi arabia background major component illness burden role impairment part recentlycompleted saudi national mental health survey snmhs compare number days role saudi population associated ten core mental disorders assessed survey associated ten commonly occurring chronic physical disordersmethodsthe snmhs household survey assessed prevalence ten common anxiety mood disruptive behavior eating disorders nationally representative sample n 1981 citizens kingdom saudi arabia ksa ages 1565 comparison information obtained prevalence ten common chronic physical disorders number healthrelated days role dor 30 days interview generalized linear models used examine univariate multivariable associations disorders dor calculate population attributable risk par separately overall disorders controlling sociodemographicsresults199 respondents one selected mental disorders 471 one selected physical disorders nine mental disorders two physical disorders associated increased dor par 329 mental disorders 270 physical disorders 599 combinedconclusionsmental disorders associated substantial proportion healthrelated dor kingdom saudi arabia programs detect treat mental disorders might lead substantially decreased role impairment kingdom,0.0
curcumin assists antiev71 activity ifn inhibiting ifnar1 reduction shsy5y cells background aimenterovirus 71 ev71 can cause severe hand foot mouth disease hfmd brain tissue involvement effective antiev71 drugs presently available clinical practice interferon ifn ineffective curcumin effective restricting ev71 replication nonneuronal cells ubiquitinproteasomemediated degradation interferonalpha receptor 1 ifnar1 protein contributes ifn resistance current study aimed determine synergistic inhibition ev71 curcumin ifn human neuroblastoma shsy5y cellsmethodsshsy5y cells infected mock curcuminpreincubated ev71 transfected plasmid containing interferonstimulated response element isre mrna containing viral internal ribosomal entry site ires following posttreatment curcumin without ifn supernatant ifn detected elisa isre irse proteasome deubiquitinating activity measured luciferase assay ev71 rna viral protein ifnar1 determined qpcr western blot respectivelyresultsev71 flailed completely block ifn production inhibited ifn signal curcumin slightly inhibited ev71 proliferation without modulating virus attachment internalization however curcumin addition restored ifnmediated isre activity thus significantly inhibiting ev71 replication furthermore ev71 also reduced ifnar1 protein proteasomedependence shsy5y cells can reversed curcumin addition evidence lowered proteasome activityconclusionthese data demonstrate curcumin assists antiev71 activity ifn inhibiting ifnar1 reduction via ubiquitinproteasome disruption shsy5y cells,0.0
identification potential autophagyrelated genes steroidinduced osteonecrosis femoral head via bioinformatics analysis experimental verification abstractpurposesteroidinduced osteonecrosis femoral head sonfh refractory orthopaedic hip joint disease occurs young middleaged people previous experimental studies shown autophagy might involved pathological process sonfh pathogenesis autophagy sonfh remains unclear aimed identify validate key potential autophagyrelated genes involved sonfh illustrate mechanism autophagy sonfh bioinformatics analysismethodsthe gse123568 mrna expression profile dataset including 10 nonsonfh following steroid administration samples 30 sonfh samples downloaded gene expression omnibus geo database autophagyrelated genes obtained human autophagy database hadb autophagyrelated genes involved sonfh screened intersecting gse123568 dataset set autophagy genes differentially expressed autophagyrelated genes involved sonfh identified r software addition gene ontology go kyoto encyclopedia genes genomes kegg pathway enrichment analyses differentially expressed autophagyrelated genes involved sonfh conducted using r software correlations expression levels differentially expressed autophagyrelated genes involved sonfh confirmed r software moreover proteinprotein interaction ppi network analysed using search tool retrieval interacting genes string significant gene cluster modules identified mcode cytoscape plugin hub genes among differentially expressed autophagyrelated genes involved sonfh screened using cytohubba cytoscape plugin finally expression levels hub genes differentially expressed autophagyrelated genes involved sonfh validated hip articular cartilage specimens necrotic femur heads nfhs using gse74089 dataset verification qrtpcrresultsa total 34 differentially expressed autophagyrelated genes identified peripheral blood samples sonfh patients nonsonfh patients based defined criteria including 25 upregulated genes 9 downregulated genes go kegg pathway enrichment analyses revealed 34 differentially expressed autophagyrelated genes involved sonfh particularly enriched death domain receptors foxo signalling pathway apoptosis correlation analysis revealed significant correlations among 34 differentially expressed autophagyrelated genes involved sonfh ppi results demonstrated 34 differentially expressed autophagyrelated genes interacted ten hub genes identified using mcc algorithms cytohubba gse74089 dataset showed tnfsf10 pten cflar significantly upregulated bcl2l1 significantly downregulated hip cartilage specimens consistent gse123568 dataset tnfsf10 pten bcl2l1 detected consistent expression qrtpcrconclusionsthirtyfour potential autophagyrelated genes involved sonfh identified via bioinformatics analysis tnfsf10 pten bcl2l1 might serve potential drug targets biomarkers regulate autophagy results expand autophagyrelated understanding sonfh might useful diagnosis prognosis sonfh,0.0
motoneuronspecific pten deletion mice induces neuronal hypertrophy also regeneration facial nerve injury postmitotic neurons several tumor suppressor genes tsgs including p53 rb pten modulate axon regeneration success injury particularly pten inhibition key driver successful cns axon regeneration optic nerve spinal cord injury contrast peripheral neurons tsg influence neuronal morphology physiology pathology investigated depth study conditionally deleted pten mouse facial motoneurons ptenflox flox chatcre analyzed neuronal responses vivo without peripheral facial nerve injury male female mice uninjured motoneurons pten loss induced somatic axonal nerve hypertrophy synaptic terminal enlargement reduction physiological whisker movement despite morphological physiological changes pten deletion positively regulated facial nerve regeneration recovery whisker movement nerve injury regenerating pten deficient motoneurons upregulated pcreb signaling pathway involving pakt ppras40 pmtor p4ebp1 aged mice 12 months pten deletion induced hair loss facial hyperplasia epidermis suggests time window younger mice pten loss stimulating axon growth injury however risk hyperplasia formation later timepoints old animaloverall data highlight dual tsg function pten loss impairing physiological neuron function furthermore underscoring positive effects pten ablation axon regeneration also pnssignificance statement tumor suppressor genes tsg restrict cell proliferation growth tsg inhibition including p53 pten stimulates axon regeneration cns injury contrast pns axon regeneration tsgs analyzed great depth herein show enhanced peripheral axon regeneration pten deletion facial motoneurons invokes signaling cascade novel pten partners including creb pras40 adult mice pten loss induces hyperplasia skin epidermis suggesting detrimental consequences reaching adulthood contrast beneficial tsg role regeneration young adult mice thus data highlight doubleedged sword nature interfering tsg function,1.0
innate chronotoxicity hypothesis ubiquitous physiological flaw unnoticed inevitable circadian rhythm evolutionary mismatch clin ter 2022 feb 7 173 1 6778 doi 107417 ct20222395abstractobjective aim study outline flaw commonly scarcely considered physiological adaptation process unnoticed can lead severe pathologies range cancer autoimmunity circadian rhythm cr disruption common factor onset diseases additional objective paper assess whether cr advantageous organisms conditions may disadvantageous measure chronotoxicity term chronotoxicity intended denote degree environment desynchronizes cr organismmethods inductive research approach adopted integrate evaluate interpret findings existing literature form verify new interpretation field research study named innate chronotoxicity ic hypothesisresults analysis cited literature provided data derive four empirical assumptions attainment ic hypothesis namely equatorial region area planet chronotoxic humans constant ld cycle corresponds human organisms internal clock cycle may therefore correctly entrain circadian rhythm chronotoxicity therefore innate inevitable considering majority humans live long way equator circadian rhythm congenital physiological feature humans circadian rhythm evolutionary mismatch since innate chronotoxicity inherently disadvantage ic intensity increases proportionally distance person lives equatorconclusions innate chronotoxicity causes remained unnoticed undetected even day although studys findings robustly validate four assumptions hypothesis confirmed rigorous research bears significant implications worlds healthcare systems due burden placed estimated population affected severity resulting related diseases entertain speculation conclusions cautiously suggested expanded view circadian pacemaker treepmid35147650 doi107417 ct20222395,0.0
genotypephenotype correlation renal lesions tuberous sclerosis complex hum genome var 2022 feb 10 9 1 5 doi 101038 s41439022001811abstracttuberous sclerosis complex tsc autosomal dominant disease caused lossoffunction mutations either two tumor suppressor genes tsc1 tsc2 mutations lead growth benign tumors hamartomas many organs including central nervous system skin kidneys investigate genotypephenotype correlation performed sequence analysis tsc1 2 genes using nextgeneration sequencing classified 30 patients tsc whose pathogenic variants identified two groups mutations producing premature termination codons ptcs missense mutations compared phenotypes two groups patients ptc significantly likely manifest major symptoms diagnostic criteria without ptc p 0035 frequencies subependymal nodules p 0026 cortical tubers p 0026 renal cysts p 0026 significantly higher ptccontaining variants cases without ptc analyses limited renal angiomyolipoma aml cases tsc2 mutations difference tumor size cases without ptc however cases ptc showed trend toward disease onset younger age multiple tumors bilateral disease observed aml lesions tsc patients ptcproducing mutations might potentially manifest severe tsc phenotypes missense mutations largerscale study appropriate samples deserves investigationpmid35145067 doi101038 s41439022001811,0.0
effects transcranial direct current stimulation cerebral glucose uptake walking report three patients multiple sclerosis front hum neurosci 2022 jan 25 16833619 doi 103389 fnhum2022833619 ecollection 2022abstractcommon symptoms multiple sclerosis ms include motor impairments lower extremities particularly gait disturbances loss balance muscle weakness representing peripheral effects shown influence symptoms however individual role cortical subcortical structures central nervous system still understood assessing 18f fluorodeoxyglucose fdg uptake cns can assess brain activity directly associated regional neuronal activity one potential modality increase cortical excitability improve motor function patients ms pwms transcranial direct current stimulation tdcs however tdcs group outcomes may mirror individual subject responses impedes knowledge pathophysiology management diseases like ms three pwms randomly received 3 ma tdcs sham targeting motor cortex m1 controls moreaffected leg 20 min separate days walking treadmill radiotracer fdg injected minute two 20 min walk subjects underwent positron emission tomography pet scan immediately task differences relative regional metabolism areas tdcs anode basal ganglia calculated investigated results indicated diverse individualized responses regions anode consistent increases basal ganglia areas eg caudate nucleus thus anodal tdcs targeting m1 controls moreaffected leg pwms might capable affecting remote subcortical regions modulating activity motor cognitive behavioral functions circuitry connected regionspmid35145388 pmcpmc8824586 doi103389 fnhum2022833619,1.0
longterm effectiveness safety tolerability fingolimod patients multiple sclerosis realworld treatment settings france virgile study neurol ther 2022 feb 11 doi 101007 s4012002200334y online ahead printabstractintroduction important confirm effectiveness tolerability diseasemodifying treatments relapsingremitting multiple sclerosis rrms realworld treatment settings prospective observational cohort study virgile performed request french health authorities primary objective evaluate effectiveness fingolimod 05 mg reducing annualised relapse rate arr patients rrmsmethods participating neurologists enrolled adult patients rrms starting fingolimod treatment 2014 2016 followed 3 years followup consultations took place investigators discretion primary outcome measure change arr month 24 fingolimod initiation relapses adverse events documented consultation disability assessment edss magnetic resonance imagery performed investigators discretionresults 1055 eligible patients 633 patients assessable month 36 405 640 treated continuously fingolimod 3 years arr decreased 092 092 inclusion 031 051 month 24 significant reduction 058 95 ci 051 065 relapses year p 0001 since starting fingolimod 461 patients 609 remained relapsefree month 24 366 patients 555 month 36 multivariate analysis previous diseasemodifying treatment number relapses previous year lower edss score inclusion associated greater ontreatment reduction arr mean edss score remained stable course study sixtyone 289 211 patients presented new radiological signs disease activity treatmentrelated serious adverse events lymphopenia n 21 bradycardia n 19 elevated transaminases n 9 macular oedema n 9 conclusions effectiveness tolerability fingolimod everyday clinical practice consistent findings previous phase iii studies study highlights utility fingolimod longterm management patients multiple sclerosispmid35147904 doi101007 s4012002200334y,0.0
detection galanin receptors spinal cord experimental autoimmune encephalomyelitis biomed pap med fac univ palacky olomouc czech repub 2022 feb 11 doi 105507 bp2022005 online ahead printabstractaims neuropeptide galanin widely distributed neurotransmitter neuromodulator regulates variety physiological processes also participates regulation stress responses aims present study investigate expression galanin receptors galr1 galr2 galr3 spinal cords murine model multiple sclerosis experimental autoimmune encephalomyelitis eae using qpcr analysis determine galr1 cellular localization oligodendrocytes microglia astrocytes ependymal cells endothelial cells capillaries immunohistochemistrymethods twelve samples eae group 14 samples control group analyzed spinal cords samples obtained peak eae diseaseresults galr1 mrna level significantly decreased eae mice compared controls p0016 whereas mrna levels galr2 galr3 significantly different eae control mice significant correlations found severity eae disease mrna levels galr1 galr2 galr3 immunochemical detection galr1 revealed expression ependymal endothelial cells additionally weak galr1 immunoreactivity occasionally detected oligodendrocytesconclusion study provides additional evidence galanin involvement eae pathophysiology investigatedpmid35147137 doi105507 bp2022005,0.0
new evidence ebv infection cause multiple sclerosis neurology 2022 feb 10101212 wnl0000000000200243 doi 101212 wnl0000000000200243 online ahead printno abstractpmid35145009 doi101212 wnl0000000000200243,0.0
proof concept use immersive virtual reality upper limb rehabilitation multiple sclerosis patients adv exp med biol 2022 13567393 doi 101007 9783030877798_4abstractmultiple sclerosis ms debilitating disease gradually reduces motor function mobility virtual reality vr successfully utilised support existing therapeutic approaches many different conditions new innovative experimental features future vr rehabilitation quest new headset oculus builtin tracking relatively low cost portability lack reliance expensive processing heavy pcs power ideal system facilitate athome clinicbased upper limb rehabilitation handtrackingbased rehabilitation game aimed people ms developed oculus quest using unity two distinct games made replicate different types hand exercises piano playing isolated finger flexion maze tracking coordination arm flexion pilot study assesses value approach along evaluating intrinsic extrinsic methods providing feedback namely positive scoring negative scoring audio response one physiotherapist two individuals ms surveyed participant response positive although small sample size impacts user testing validity results future research recommended build data gathered pilot study increase sample size collect richer feedbackpmid35146618 doi101007 9783030877798_4,0.0
autologous hematopoietic stem cell transplantation vs lowdose immunosuppression secondaryprogressive multiple sclerosis eur j neurol 2022 feb 11 doi 101111 ene15280 online ahead printabstractbackground effectiveness autologous haematopoietic stemcell transplantation ahsct relapsingremitting multiple sclerosis ms well known secondaryprogressive sp ms still controversial therefore ahsct activity evaluated spms using lowdose immunosuppression cyclophosphamide cy comparative treatmentmethods retrospective monocentric 12 matched study spms patients treated beamahsct cases iv pulses cy controls single academic centre florence controls selected according baseline characteristics adopting cardinality matching trimming estimated propensityscore kaplanmeier cox analyses used estimate survival free relapses rfs disability progression pfs neda2results 93 spms included 31 ahsct 62 cy mean followup 99 months ahsct 91 months cy groups rfs higher ahsct compared cy patients year 5 100 vs 52 respectively p00001 pfs differ groups year 5 70 ahsct 81 cy p0572 neda2 p0379 sensitivity analysis including 31 bestmatched controls confirmed results three neoplasms 2 cy 1 ahsct two fatalities 2 cy occurredconclusion study provides class iii evidence spms superior effectiveness ahsct compared cy relapse activity without differences disability accrual despite suppression relapses observed ahsct group ahsct show advantages cy disability suggesting spms disability progression becomes based noninflammatory neurodegeneration inflammationpmid35146841 doi101111 ene15280,0.0
evolution disease modifying therapy benefits risks argument deescalation treatment paradigm patients multiple sclerosis front neurol 2022 jan 25 12799138 doi 103389 fneur2021799138 ecollection 2021abstractbackground strategies sequencing disease modifying therapies dmts multiple sclerosis ms patients include escalation high efficacy early induction deescalationobjective provide perspective deescalation aims match ratio dmt benefit risk aging patientsmethods reanalyzed data retrospective realworld cohort ms patients model disease activity oral dimethyl fumarate fingolimod higher efficacy infusible natalizumab rituximab dmts age patients relapsing ms conducted controlled stratified analysis examining odds disease activity oral vs infusible dmts patients 45 45 years reviewed literature identify dmt risks predictors safe discontinuationresults younger patients lower probability disease activity infusible vs oral dmts statistical difference age 542 years dichotomized patients 45 years oral dmts greater odds disease activity compared patients infusible dmts among 45 years difference literature review noted adverse events increase aging notably infections patients higher disability longer dmt duration additionally identified factors predictive disease reactivation including age clinical stability mri activityconclusion realworld cohort relapsing ms patients high efficacy dmts less benefit aging associated increased risks cohort helps overcome limitations trials older patients excluded better balance benefits risks propose dmt deescalation approach aging ms patientspmid35145470 pmcpmc8821102 doi103389 fneur2021799138,0.0
pharmacological blockade kv13 channel promising treatment autoimmune diseases j transl autoimmun 2022 jan 24 5100146 doi 101016 jjtauto2022100146 ecollection 2022abstractthere 100 autoimmune diseases ad high prevalence ranges 5 8 general population type diabetes mellitus multiple sclerosis systemic lupus erythematosus rheumatoid arthritis remain health problem highest concern among people worldwide due high morbidity mortality development new treatment strategies become research hotspot recent years study ion channels presents cells immune system regarding functional role consequences mutations genes different ways blocking subject intense research pharmacological blockade kv13 channel inhibits ca2+ signaling t cell proliferation proinflammatory interleukins production human cd4+ effector memory t cells cells mediated ad inhibition promising therapeutic target review will highlight biological function kv13 channel t cells consequence pharmacological inhibition anemone scorpion toxins synthetic peptides nanoparticles monoclonal antibodies well possible therapeutical application adpmid35146402 pmcpmc8818563 doi101016 jjtauto2022100146,0.0
vascular dysfunction dyslipidemia multiple sclerosis correlated disease duration disability status egypt heart j 2022 feb 11 74 1 9 doi 101186 s43044022002442abstractbackground strong evidence vascular dysfunction considered one possible causes morbidity mortality patients suffering multiple sclerosis ms work aimed assessing arterial function serum lipids ms patients correlating clinical radiological findingsresults casecontrol study included 50 patients ms 50 age sexmatched controls arterial function significantly reduced ms patients confirmed significantly higher pulse wave velocity pwv augmentation index aix carotid imt show significant difference two groups plaques patients significant positive correlation found pwv disease duration disability ms patients significantly higher serum levels tcholesterol triglycerides significantly lower serum levels hdlcholesterol compared controls significant correlation found serum lipids either disease duration disabilityconclusions significant impairment arterial function assessed brachial cuffbased method via mobilograph device ms patients compared controls impairment significantly correlated disease duration disability ms patients also significantly higher levels tcholesterol triglycerides compared controls significant correlation serum lipids either disease duration disabilitypmid35147792 doi101186 s43044022002442,0.0
increasing patient safety among multiple sclerosis ms drug dalfampridine users expanding awareness serious side effects cureus 2022 jan 3 14 1 e20884 doi 107759 cureus20884 ecollection 2022 janabstractdalfampridine drug used improve walking multiple sclerosis ms patients approved 2010 contraindicated patients history seizures renal disease case report present patient either contraindications yet seizure episode contributing factor use dalfampridinepmid35145789 pmcpmc8808083 doi107759 cureus20884,0.0
selfperceived versus physician documented adverse events patients multiple sclerosis regims pharmacovigilance registry patients multiple sclerosis germany abstractbackgroundpostmarketing studies including registries mark indispensable step establishment drug sideeffect profiles recent years inclusion patientsnull perspective gained increasing relevance regarding pharmacovigilanceobjectiveprimary objective study analyse concordance subjectively experienced symptoms multiple sclerosis ms patients treated immunotherapy adverse events reported treating physiciansmethodsregims data source study prospective registry investigating longterm drug safety treatment ms germany patients included meet revised mcdonald criteria 2005 treated immunotherapy concordance adverse events documented six 12 months baseline presentation 642 ms patients 46 different neurologic outpatient centres germany analysed physiciansnull documentation done either paper electronically routine visits patientsnull selfreports based mailed questionnaires regression models used analyse factors influencing reportingresultsduring one year followup patients reported total number 4 841 events per 1 000 patientyears pys physicians reported 467 events 1 000 pys patientsnull physiciansnull reports focused different body functions categories respectively factors increasing patientsnull likeliness report female gender coefficient 152 95 ci 096 209 history smoking 080 95 ci 013 147 higher edss score 028 95 ci 010 046 previous ms therapies 035 95 ci 011 059 increased patientsnull reporting aes physicians likely report ae fingolimod interferon beta preparations or322 95 ci 122 852 discussionunderreporting adverse events known problem clinical routine several years without signs substantial improvement encouraging patientsnull involvement adverse event reporting offers possibility holistic approach pharmacovigilance investigations patientsnull physiciansnull strategies comes causality assessment adverse events related ms medication may insightful,0.0
impact prenatal childhood adversityeffects around world war ii multimorbidity results koraage study background risk factors agerelated diseases may increase multimorbidity mm early life deprivation may also accelerate development chronic diseases mmmethodsthis study explores prevalence pattern mm 6571 yearold individuals born world war ii southern germany based two large crosssectional kora cooperative health research region augsburg age studies 2008 9 2016 mm defined least two chronic diseases birth periods classified five phases prewar early war late war famine famine period logistic regression models used analyze effect birth phases mm adjustment sociodemographic lifestyle risk factors furthermore used agglomerative hierarchical clustering investigate cooccurrence diseasesresultsparticipants born late war phase highest prevalence mm 622 single chronic diseases compared participants born phases born late war phase significantly associated higher odds mm 183 95 ci 115291 adjustment sociodemographic lifestyle factors women prevalence joint gastrointestinal eye diseases anxiety higher heart disease stroke diabetes common men moreover three main chronic disease clusters responsible observed associations identified joint psychosomatic cardiometabolic internal organ diseasesconclusionsour findings imply adverse earlylife exposure may increase risk mm adults aged 6571 years moreover identified disease clusters coincidental require investigation,0.0
effect acceptance commitment therapy mood sleep quality quality life menopausal women randomized controlled trial background one critical periods womans life menopause menopause depression anxiety among common mood changes sleep disorders also increase menopause leads quality life disorders different methods medication psychotherapy combination used treat disorders acceptance commitmentbased therapy one newest methods psychotherapy recently used lot therefore study conducted determine effect acceptance commitment therapy act mood primary outcome sleep quality quality life secondary outcomes menopausal womenmethodsthis randomized controlled trial performed 86 menopausal women tabriz iran 2021 using blocking method participants randomly assigned intervention control groups intervention group received counseling based act approach 8 sessions 60 90 min control group received routine health care depression anxiety stress scale21 dass 21 menopause quality life menqol pittsburgh sleep quality index psqi questionnaires completed intervention immediately intervention independent ttest mannwhitney u test used compare outcomes two groupsresultsin terms sociodemographic characteristics baseline values studied variables statistically significant difference study groups intervention end intervention mean sd standard deviation scores anxiety stress depression counseling group 266 128 291 162 198 159 control group 419 185 561 149 359 191 intervention group mean score three variables significantly lower control group p 0001 intervention mean sd total sleep quality score 404 252 counseling group 413 263 control group addition mean sd total quality life score 2347 2013 counseling group 2314 1776 control group study groups statistically significant differences mean overall score sleep quality p 0867 overall score quality life p 0759 conclusionusing actbased counseling can improve mood menopausal women however randomized clinical trials needed making definitive conclusionstrial registrationiranian registry clinical trials irct irct20120718010324n65 date registration 2 19 2021 date first registration 2 19 2021 url https enirctir user trial 53544 view date recruitment start date 2 22 2021,0.0
methotrexateloaded nanoparticles ameliorate experimental model autoimmune arthritis regulating balance interleukin17producing t cells regulatory t cells background rheumatoid arthritis ra progressive systemic autoimmune disease characterized infiltration inflammatory cells hyperplastic synovial tissue resulting subsequent destruction adjacent articular cartilage bone methotrexate mtx first conventional diseasemodifying antirheumatic drug dmard alleviate articular damage ra implicated humoral cellular immune responses however mtx several side effects efficient delivery lowdose mtx importantmethodsto investigate efficacy mtxloaded nanoparticles mtxnps experimental model ra free mtx mtxnps administered subcutaneous route mice collageninduced arthritis cia 3 weeks cii immunization levels inflammatory factors tissues determined immunohistochemistry confocal microscopy realtime pcr flow cytometryresultsmtxnps ameliorated arthritic severity joint destruction collageninduced arthritis cia mice compared free mtxtreated cia mice levels inflammatory cytokines including interleukin il 1 tumor necrosis factor vascular endothelial growth factor reduced mtxnpstreated mice number cd4 + il17 + cells decreased whereas number cd4 + cd25 + foxp3 + cells increased spleens mtx npstreated cia mice compared mtxtreated cia mice frequency cd19 + cd25 + foxp3 + regulatory b cells increased ex vivo splenocytes mtxloaded npstreated cia mice compared mtxtreated cia miceconclusionthe results suggest mtxloaded nps therapeutic potential ra,0.0
diagnosis genotypephenotype correlation patients pkd1#x2f tsc2 contiguous gene deletion syndrome clin nephrol 2022 feb 10 doi 105414 cn110476 online ahead printabstractdeletions involving tsc2 pkd1 genes lead tuberous sclerosis complex tsc autosomal dominant polycystic kidney disease adpkd known tsc2pkd1 contiguous gene deletion syndrome pkdts pkdts leads severe symptoms death reported cases pkdts phenotypic descriptions poor detailed statistics descriptions time onset prognosis pkdts lacking first study report clinical data pkdts patients china analyzed cases including chinese individuals summarized clinical manifestations genetic characteristics study first use combination exome sequencing multiplex ligationdependent probe amplification mlpa screen diagnose pkdts found many pkdts patients following multiple renal cysts angiofibromas 3 fibrous cephalic plaque subependymal nodules seizures intellectual disability pkdts develops polycystic kidney disease birth 17 years old time occurrence endstage renal disease dialysis 2162 1287 years age significantly earlier adpkd caused pkd1 mutation compared nonchinese individuals diverse ancestry chinese people significant differences clinical characteristics including ungual fibromas 2 shagreen patch five novel large deletions identified chinese found relationship clinical phenotype genotype combined exome sequencing mlpa develop diagnostic method pkdtspmid35142283 doi105414 cn110476,0.0
linking epsteinbarr virus infection multiple sclerosis nat rev immunol 2022 feb 9 doi 101038 s41577022006864 online ahead printno abstractpmid35140366 doi101038 s41577022006864,0.0
cortical lesion hotspots association subpial lesions disability multiple sclerosis mult scler 2022 feb 1013524585211069167 doi 101177 13524585211069167 online ahead printabstractbackground dramatic improvements visualization cortical especially subpial multiple sclerosis ms lesions allow assessment impact clinical courseobjective characterize cortical lesions 7 tesla t t2 t1weighted magnetic resonance imaging mri determine relationship ms pathology contribution disabilitymethods sixtyfour adults ms 45 relapsingremitting 19 progressive underwent 3 t brain spine mri 7 t brain mri clinical testingresults cortical lesions found 94 progressive median 56 range 2203 relapsingremitting 15 0168 p 0004 lesion distribution across 50 cortical regions nonuniform p 0006 highest lesion burden supplementary motor cortex highest prevalence superior frontal gyrus leukocortical white matter lesion volumes strongly correlated r 058 p 00001 subpial white matter lesion volumes moderately correlated r 030 p 0002 leukocortical p 002 subpial lesions p 040 correlated paramagnetic rim lesions correlated spinal cord lesions p 001 cortical lesion volumes total subtypes correlated expanded disability status scale 25foot timed walk ninehole peg test symbol digit modality test scoresconclusion cortical lesions highly prevalent associated disability progressive disease subpial lesion burden strongly correlated white matter lesions suggesting differences inflammation repair mechanismspmid35142571 doi101177 13524585211069167,0.0
trpmls tpcs targets lysosomal storage neurodegenerative disease therapy cell calcium 2022 feb 5 103102553 doi 101016 jceca2022102553 online ahead printabstractneurodegenerative diseases nd pose serious health burden society healthcare systems alike increasing incidence rates especially within aging populations alzheimers disease ad prevalent type nd dementia followed parkinsons disease pd multiple sclerosis amyotrophic lateral sclerosis huntingtons disease progressive neurological dysfunction regional neuronal loss constitute common characteristics nd many nd accompanied accumulation protein aggregates extracellular amyloid ad intraneuronal hyperphosphorylated tau ad synuclein pd two main systems responsible clearance damaged dysfunctional senescent proteins inside cells autophagylysosomal pathway ubiquitinproteasome system importance lysosomes neurodegenerative processes highlighted clinical phenotypes lysosomal storage disorders lsds comprising 70 inheritable diseases caused mutations lysosomal enzymes lysosomal membrane proteins often resulting severe neurodegeneration dysfunctional lysosomal proteins enzymes result lysosomal accumulation undigested macromolecules eg lipids glycoproteins glycosaminoglycans gangliosides defects intracellular transport pathways involving endosomes lysosomes increasingly recognized drivers neurodegenerative disease pathology including ad pd thus accumulation damaged proteins organelles eg mitochondria neurons glial cells overwhelms capacity intracellular recycling degradation mechanisms exacerbating disease pathology endolysosomal ion channels recently established important regulators lysosomal exocytosis ion homeostasis ph endolysosomal trafficking fusion fission autophagy particular two nonselective endolysosomal cation channel families mucolipin trpml mcoln channels twopore channels tpcs will discussed potential pharmacological targets lsd nd treatmentpmid35144097 doi101016 jceca2022102553,0.0
optimizing eeg source reconstruction concurrent fmriderived spatial priors brain topogr 2022 feb 10 doi 101007 s10548022008913 online ahead printabstractreconstructing eeg sources involves complex pipeline inverse problem challenging multiple inversion algorithms continuously developed aiming tackle nonuniqueness problem shown partially circumvented including prior information inverse models despite efforts still current persistent controversies regarding inversion algorithm choice optimal set spatial priors included inversion models use simultaneous eegfmri data one approach tackle problem spatial resolution fmri makes fmri derived spatial priors convenient eeg reconstruction however task activation maps restingstate networks rsns explored far overlooking recent already accepted notion brain networks exhibit dynamic functional connectivity fluctuations lack systematic comparison different source reconstruction algorithms considering potentially braininformative priors fmri motivates search better reconstruction models using simultaneous eegfmri data compared four different inversion algorithms minimum norm mn low resolution electromagnetic tomography loreta empirical bayes beamformer ebb multiple sparse priors msp bayesian framework implemented spm three different sets priors consisting 1 specific algorithm 2 specific algorithm plus fmri task activation maps rsns 3 specific algorithm plus fmri task activation maps rsns network modules taskrelated dfc states estimated dfc fluctuations quality reconstructed eeg sources quantified terms modelbased metrics namely expectation posterior probability p model data variance explained inversion models overlap proportion brain regions known involved visual perception tasks participants submitted rsn templates within eeg source components modelbased metrics suggested model parsimony preferred combination msp priors specific algorithm exhibiting best performance however optimal overlap proportion values found using ebb priors specific algorithm fmri task activation maps rsns msp considering priors algorithm priors fmri task activation maps rsns dfc state modules respectively indicating fmri spatial priors including dfc state modules might contain useful information recover eeg source components reflecting neuronal activity interest main results show providing fmri spatial derived priors reflect dynamics brain might useful map neuronal activity accurately eegfmri furthermore work paves way towards informative selection optimal eeg source reconstruction approach may critical future studiespmid35142957 doi101007 s10548022008913,0.0
evaluation s100a12 apoa1 plasma level potency untreated new relapsingremitting multiple sclerosis patients family members sci rep 2022 feb 9 12 1 2160 doi 101038 s41598022063224abstractmultiple sclerosis inflammatory disease spinal cord brain receptor advanced glycation end products apolipoprotein a1 apoai recommended pathogenic role neuroinflammatory disorder multiple sclerosis purpose research measure plasma levels s100a12 apoa1 firstdegree family relapsingremitting multiple sclerosis rrms patients plasma levels s100a12 apoa1 evaluated via enzymelinked immunosorbent assay thirtyfive new cases untreated patients deterministic rrms according mcdonald criteria twentyfour healthy controls twentysix firstdegree members untreated rrms patients called highrisk group main findings study follows plasma level s100a12 significantly lower new cases untreated rrms p 005 0045 highrisk p 005 0001 groups although plasma protein level apoa1 reduced significantly highrisk group p 005 p 0003 compared healthy control group significant difference untreated rrms patients p 0379 plasma level vitamin d3 rrms patients highrisk groups displayed significance reduction although significant association vitamin d s100a12 apoa1 levels given role s100a12 apoa1 inflammatory process performed firstdegree family members rrms patients revealed significant decrease group concluded can considered one contributing factors pathogenesis ms though research needed assuming predictive biomarkerspmid35140322 doi101038 s41598022063224,0.0
tyrphostin a9 protects axons experimental autoimmune encephalomyelitis activation erks life sci 2022 feb 7120383 doi 101016 jlfs2022120383 online ahead printabstractaims small molecule compound tyrphostin a9 a9 inhibitor plateletderived growth factor pdgf receptor previously reported group stimulate extracellular signalregulated kinase 1 erk1 2 erk2 neuronal cells pdgf receptorirrelevant manner study aimed investigate whether a9 protect axons experimental autoimmune encephalomyelitis activation erksmain methods a9 treatment protection neurite outgrowth shsy5y neuroblastoma cells primary substantia nigra neuron cultures neurotoxin mpp+ analyzed clinical symptoms well erk1 2 activation axonal protection induction abundance increases regeneration biomarker gap43 cns relapsingremitting experimental autoimmune encephalomyelitis eae model verifiedkey findings a9 treatment stimulate neurite outgrowth shsy5y neuroblastoma cells protect primary substantia nigra neuron cultures neurotoxin mpp+ relapsingremitting eae model oral administration a9 successfully ameliorated clinical symptoms activated erk1 2 induced axonal protection increased abundance regeneration biomarker gap43 cns interestingly gene deficiency erk1 erk2 disrupted beneficial effects a9 mog3555induced eaesignificance results demonstrated small molecule compounds stimulate persistent erk activation vitro vivo may useful protective restorative treatment neurodegenerative diseasespmid35143827 doi101016 jlfs2022120383,0.0
sec13 promotes oligodendrocyte differentiation myelin repair autocrine pleiotrophin signaling j clin invest 2022 feb 10e155096 doi 101172 jci155096 online ahead printabstractdysfunction protein trafficking intensively associated neurological diseases including neurodegeneration whether protein transport contributes oligodendrocyte maturation myelin repair white matter injury remains unclear ertogolgi trafficking newly synthesized proteins mediated coat protein complex ii copii complex demonstrate copii component sec13 essential oligodendrocyte differentiation postnatal myelination ablation sec13 oligodendrocyte lineage prevented opc differentiation inhibited myelination remyelination demyelinating injury central nervous system cns improving protein traffic tauroursodeoxycholic acid tudca ectopic expression copii components accelerated myelination copii components upregulated oligodendrocyte lineage cells demyelinating injury loss sec13 altered secretome oligodendrocytes inhibited secretion ptn identified function autocrine factor promote oligodendrocyte differentiation myelin repair data suggest sec13dependent protein transport essential oligodendrocyte differentiation sec13mediated ptn autocrine signaling required proper myelination remyelinationpmid35143418 doi101172 jci155096,1.0
causal relationship gut microbiota autoimmune diseases twosample mendelian randomization study front immunol 2022 jan 24 12746998 doi 103389 fimmu2021746998 ecollection 2021abstractbackground growing evidence shown alterations gut microbiota composition associated multiple autoimmune diseases ads however unclear whether associations reflect causal relationshipobjective reveal causal association gut microbiota ad conducted twosample mendelian randomization mr analysismaterials methods assessed genomewide association study gwas summary statistics gut microbiota six common ads namely systemic lupus erythematosus rheumatoid arthritis inflammatory bowel disease multiple sclerosis type 1 diabetes t1d celiac disease ced published gwass twosample mr analyses first performed identify causal bacterial taxa ads discovery samples significant bacterial taxa replicated independent replication outcome samples series sensitivity analyses performed validate robustness results finally reverse mr analysis performed evaluate possibility reverse causationresults combining results discovery replication stages identified one causal bacterial genus bifidobacterium higher relative abundance bifidobacterium genus associated higher risk t1d odds ratio 1605 95 ci 13391922 pfdr 419 107 ced 1401 95 ci 11391722 pfdr 203 103 respectively sensitivity analyses validated robustness associations results reverse mr analysis showed evidence reverse causality t1d ced bifidobacterium genusconclusion study implied causal relationship bifidobacterium genus t1d ced thus providing novel insights gut microbiotamediated development mechanism adspmid35140703 pmcpmc8819003 doi103389 fimmu2021746998,0.0
plasma microrna vary association progression alzheimer#39 s disease alzheimers dement amst 2022 feb 5 14 1 e12251 doi 101002 dad212251 ecollection 2022abstractintroduction early intervention alzheimers disease ad requires development easily administered test able identify risk focusing microrna robustly detected plasma standardizing analysis strategy sought identify diseasestage specific biomarkersmethods using taqman microfluidics arrays statistical consensus approach assessed plasma levels 185 neurodegenerationrelated microrna cohorts cognitively normal amyloid positive cna+ mild cognitive impairment mci alzheimers disease ad participants relative respective controlsresults distinct disease stage microrna biomarkers identified shown predict membership groups area curve auc 08 altered dynamically ad progression longitudinal study bioinformatics demonstrated microrna target known adrelated pathways phosphoinositide 3kinase pi3kakt signalling pathway furthermore significant correlation found mir27a3p mir27b3p mir3245p amyloid beta loaddiscussion results show microrna signatures alter throughout progression ad reflect underlying disease pathology may prove useful diagnostic markerspmid35141392 pmcpmc8817674 doi101002 dad212251,0.0
natalizumab treatment pregnancy multiple sclerosisclinical bioethical aspects ongoing debate wien med wochenschr 2022 feb 10 doi 101007 s10354022009136 online ahead printabstractbackground natalizumab approved treatment relapsing remitting multiple sclerosis however safety pregnancy formally provencase presentation report woman multiple sclerosis treated natalizumab pregnancy withdrawal natalizumab suffered severe disabling rebound agreement patient natalizumab restarted pregnancy patient improved substantially gave birth healthy boyconclusion use natalizumab pregnancy may option highly active multiple sclerosispmid35142953 doi101007 s10354022009136,0.0
window opportunity therapeutic use vitamin d multiple sclerosis neural regen res 2022 sep 17 9 19451954 doi 104103 16735374335139abstractmultiple sclerosis autoimmune treatable curable disease multiplicity medications multiple sclerosis therapy including class entitled diseasemodifying drugs mainly indicated reduce number severity disease relapses patients respond well therapies minor severe adverse effects reported vitamin d called sunshine vitamin studied possible light end tunnel review recapitulated similar immunopathogenesis multiple sclerosis experimental autoimmune encephalomyelitis immunomodulatory neuroprotective potential vitamin d stateofart concerning supplementation multiple sclerosis patients finally based groups experimental findings analyzed need consider relevance route different timepoint administration aspects rational indication vitamin multiple sclerosis patientspmid35142671 doi104103 16735374335139,1.0
mediterranean diet associated multiple sclerosis related symptoms fatigue severity nutr neurosci 2022 feb 1017 doi 101080 1028415x20222034241 online ahead printabstractobjective nutrition modulation can reduce multiple sclerosis ms related symptoms fatigue severity mediterranean diet may beneficial regarding antiinflammatory components however previous studies limited study aims investigate relationship mediterranean diet adherence msrelated symptoms fatigue severitymethods one hundred two adult ms patients enrolled crosssectional study dietary adherence assessed using mediterranean diet assessment tool medas msrelated symptoms determined using msrelated symptom checklist msrs fatigue severity scale fss applied linear regression models established assess predicted factors msrs fssresults mean age participants 331 981 years female higher education degree 716 608 respectively linear regression model medas associated msrs negatively associated fss scores msrs scores significantly higher among participants consumed one serving red meat products per day consumed less one serving butter margarine cream per day reported lower fss scores trend significances shown consume limited sweet lower fss scores likewise msrs scores lower three serving week intake fishconclusion following mediterraneanstyle diet encouraged improve fatigue severity components reduced consumption red meat saturated fatty acids sweets increased fish consumption promising reduce ms symptoms fatigue severity findings proven intervention studiespmid35143375 doi101080 1028415x20222034241,0.0
genistein review antiinflammatory properties front pharmacol 2022 jan 24 13820969 doi 103389 fphar2022820969 ecollection 2022abstractnowadays nonresolving inflammation becoming major trigger various diseases plays significant role pathogenesis atherosclerosis asthma cancer obesity inflammatory bowel disease chronic obstructive pulmonary disease neurodegenerative disease multiple sclerosis rheumatoid arthritis however prolonged use antiinflammatory drugs usually accompanied undesirable effects hence patients tend seek natural compounds alternative medicine considering fact urgency discover develop potential novel safe efficacious natural compounds drug candidates future antiinflammatory therapy genistein belongs flavonoid family subgroup isoflavones phytoestrogen mainly derived legumes naturally occurring chemical constituent similar chemical structure mammalian estrogens claimed exert many beneficial effects health protection osteoporosis reduction risk cardiovascular disease alleviation postmenopausal symptoms anticancer properties past numerous vitro vivo studies conducted investigate antiinflammatory potential genistein henceforth review aims summarize antiinflammatory properties genistein linking signaling pathways mediators involved inflammatory response well toxicity profile current outcomes analysed highlight prospect lead compound drug discovery data collected using pubmed sciencedirect springerlink scopus databases results showed genistein possessed strong antiinflammatory activities inhibition various signaling pathways nuclear factor kappab nfb prostaglandins pgs inducible nitric oxide synthase inos proinflammatory cytokines reactive oxygen species ros comprehensive assessment mechanism action antiinflammatory effects genistein included however evidence pharmacological effects still lacking studies using various animal models assess pharmacological effects toxicity pharmacokinetics pharmacodynamics bioavailability studies required clinical studies can conducted review will highlight potential use genistein lead compound future drug development antiinflammatory agentpmid35140617 pmcpmc8818956 doi103389 fphar2022820969,0.0
can predict patients plantar heel pain likely benefit insoles secondary exploratory analysis randomized controlled trial background plantar heel pain php common cause foot complaints treatment custommade insoles frequently applied far studies investigated patient characteristics predict response treatments aim secondary exploratory analysis twofold firstly identify patient characteristics predict prognosis patients php treated insoles secondly identify characteristics might interact treatment insolesmethodsdata randomized trial participants received either custom insoles n 70 sham insoles n 69 used baseline information collected demographics foot symptoms foot ankle range motion navicular drop presence neuropathic pain physical activity illnesses last 12 months primary outcome study foot function index score ffi 26 weeks multivariable linear regression models generated identify patients characteristics predict outcome type intervention ie insoles gpled usual care resultswe found two variables associated better function score 26 weeks patients treated insoles female sex 959 95ci 1787 131 lower ffi score baseline 056 95ci 030 082 explorative analyses patients treated insoles showed significant interaction effects type insole custommade versus sham potential predictive factorsconclusionwhen communicating effect insoles php clinicians take sex amount pain disability first presentation account women people better foot function scores baseline according ffi might respond better treatment insoles terms foot functiontrial registrationtrial registration ntr5346,0.0
sphingosine1 phosphate receptor 1 contributes central sensitization recurrent nitroglycerininduced chronic migraine model background central sensitization important pathophysiological mechanism chronic migraine cm microglia activation trigeminocervical complex tcc contributes development central sensitization emerging evidence implicates blocking sphingosine1phosphate receptor 1 s1pr1 can relieve development chronic pain inhibit activation microglia however unclear whether s1pr1 involved central sensitization cm therefore purpose study explore role s1pr1 downstream signal transducers activators transcription 3 stat3 signaling pathway cm mainly inflammationmethodschronic intermittent intraperitoneal injection nitroglycerin ntg established mouse model cm first observed changes subcellular localization s1pr1 trigeminocervical complex tcc w146 s1pr1 antagonist sew2871 s1pr1 agonist ag490 stat3 inhibitor applied intraperitoneal injection investigate related molecular mechanism changes number microglia expression calcitonin generelated peptide cgrp cfos tcc site explored immunofluorescence addition studied effect s1pr1 inhibitors stat3 lipopolysaccharidetreated bv2 microgliaresultsour results showed expression s1pr1 increased ntg injection s1pr1 colocalized neurons glial cells tcc s1pr1 antagonist w146 alleviated ntginduced hyperalgesia suppressed upregulation cgrp cfos pstat3 tcc importantly blocking s1pr1 reduced activation microglia addition found inhibiting stat3 signal also attenuated ntginduced basal mechanical thermal hyperalgesiaconclusionsour results indicate inhibiting s1pr1 signal alleviate central sensitization inhibit microglia activity caused chronic ntg administration via stat3 signal pathway provide new clue clinical treatment cm,0.0
central nervous system macrophages progressive multiple sclerosis relationship neurodegeneration therapeutics abstractthere 15 diseasemodifying drugs approved last 20 years treatment relapsingremitting multiple sclerosis ms limited treatment options available progressive ms development new drugs treatment progressive ms remains challenging pathophysiology progressive ms poorly understoodthe progressive phase ms dominated neurodegeneration heightened innate immune response trapped immune cells behind closed bloodbrain barrier central nervous system review microglia borderassociated macrophages include perivascular meningeal choroid plexus macrophages progressive phase ms cells vital largely basis define lesion types ms will review evidence reactive microglia macrophages upregulate proinflammatory genes downregulate homeostatic genes may promote neurodegeneration progressive ms will also review factors regulate microglia macrophage function progressive ms well potential toxic functions cells diseasemodifying drugs solely target microglia macrophage progressive ms lacking recent treatment successes progressive ms include include bcell depletion therapies sphingosine1phosphate receptor modulators will describe several therapies evaluated potential treatment option progressive ms immunomodulatory therapies can target myeloid cells potential neuroprotective agent,1.0
neurofilament light chain determination referee future vitamin d3 supplementation multiple sclerosis neuroimmunomodulation 2022 feb 913 doi 101159 000521266 online ahead printno abstractpmid35139509 doi101159 000521266,0.0
attrition within digital health interventions people multiple sclerosis systematic review metaanalysis j med internet res 2022 feb 9 24 2 e27735 doi 102196 27735abstractbackground digital health interventions revolutionized multiple sclerosis ms care supporting people ms better selfmanage disease now understood technological elements comprise category digital health interventions can influence participant engagement selfmanagement programs people ms can experience significant barriers influenced elements remaining engaged period learning essential explore influence technological elements mitigating attritionobjective study aimed examine study design technological elements documented digital health interventions targeted people msdigital health interventions intended support program engagement defined periodand explore correlated attrition among participants randomized controlled trials rcts methods conducted systematic review metaanalysis rcts n32 describing digital health selfmanagement interventions people ms analyzed attrition included studies using randomeffects model metaregression measure association potential moderatorsresults measured differences attrition intervention control arms however heterogeneity observed explained composite technological element score pooled attrition rates intervention control arms 147 156 respectivelyconclusions paper provides insight technological composition digital health interventions designed people ms describes degree attrition study arms paper will aid design future studies area particularly digital health interventions typepmid35138262 doi102196 27735,0.0
ctype lectin receptor clec1a plays important role development experimental autoimmune encephalomyelitis enhancing antigen presenting ability dendritic cells inducing inflammatory cytokine il17 exp anim 2022 feb 8 doi 101538 expanim210191 online ahead printabstractclec1a member ctype lectin receptor family carbohydrate recognition domain extracellular region known signaling motif cytoplasmic domain clec1a highly expressed endothelial cells weakly dendritic cells although molecule reported play important role host defense aspergillus fumigatus recognizing 1 8dihydroxynaphthalenemelanin fungal surface roles molecule uninfected animals remain elucidated study found clec1a mice develop milder symptoms upon induction experimental autoimmune encephalomyelitis eae animal model multiple sclerosis maximum disease score significantly lower demyelination inflammation spinal cord much milder clec1a mice compared wildtype mice abnormality detected immune cell composition draining lymph nodes spleen day 10 16 eae induction recall memory t cell proliferation restimulation myelin oligodendrocyte glycoprotein peptide mog3555 vitro decreased clec1a mice antigen presenting ability clec1a dendritic cells impaired interestingly rnaseq rtqpcr analyses clearly showed expression inflammatory cytokines including il17a il6 il1b greatly decreased clec1a mice induction eae suggesting reduced cytokine production responsible amelioration eae clec1a mice observations suggest novel function clec1a immune systempmid35135958 doi101538 expanim210191,1.0
exploring role stem cell therapy treating neurodegenerative diseases challenges current perspectives curr stem cell res ther 2021 aug 9 doi 102174 1574888x16666210810103838 online ahead printabstractseveral human neurological disorders parkinsons disease alzheimers disease amyotrophic lateral sclerosis huntingtons disease spinal cord injury multiple sclerosis brain stroke caused injury neurons glial cells recent years witnessed successful generation neurons glia cells driving efforts develop stemcellbased therapies patients combat broad spectrum human neurological diseases inadequacy suitable cell types cell replacement therapy patients suffering neurological disorders hampered development promising therapeutic approach attempts thus made reconstruct viable neurons glial cells different stem cells embryonic stem cells mesenchymal stem cells neural stem cells dedicated research cultivate stem cellbased brain transplantation therapies carried aim compiling breakthroughs field stem cellbased therapy treatment neurodegenerative maladies emphasizing shortcomings faced victories achieved future prospects therapy clinical settingspmid35135462 doi102174 1574888x16666210810103838,1.0
itaconate fumarate derivatives inhibit priming activation canonical nlrp3 inflammasome macrophages immunology 2022 feb 9 doi 101111 imm13454 online ahead printabstractthe nlrp3 inflammasome multiprotein complex regulates caspase1 activation subsequent interleukin il 1 il18 release innate immune cells response infection injury derivatives metabolites itaconate fumarate dimethyl itaconate dmi 4octyl itaconate 4oi dimethyl fumarate dmf limit expression release il1 following nlrp3 inflammasome activation however direct effects metabolite derivatives nlrp3 inflammasome responses require investigation using murine bone marrowderived macrophages mixed glia organotypic hippocampal slice cultures ohscs demonstrate dmi 4oi dmf pretreatment inhibit proinflammatory cytokine production response lipopolysaccharide lps well inhibiting subsequent nlrp3 inflammasome activation induced nigericin dmi 4oi dmf monomethyl fumarate mmf another fumarate derivative also directly inhibited biochemical markers nlrp3 activation lpsprimed macrophages mixed glia ohscs human macrophages response nigericin imiquimod including asc speck formation caspase1 activation gasdermin d cleavage il1 release dmf approved treatment multiple sclerosis well dmi 4oi mmf inhibited nlrp3 activation macrophages response lysophosphatidylcholine used induce demyelination suggesting possible mechanism dmf multiple sclerosis nlrp3 inhibition derivatives also reduced proil1 cleavage response calcium ionophore ionomycin together findings reveal immunometabolic regulation priming activation steps nlrp3 activation macrophages furthermore highlight itaconate fumarate derivatives potential therapeutic options nlrp3 il1driven diseases including brainpmid35137954 doi101111 imm13454,1.0
unusual primary central nervous system tcell#x2f histiocyterich large bcell lymphoma case report bmj case rep 2022 feb 8 15 2 e246355 doi 101136 bcr2021246355abstractwe report case 54yearold immunocompetent woman presented primary tcell histiocyterich large bcell lymphoma tchrlbcl central nervous system without systemic involvement diagnosed means brain biopsy treated corticosteroids subsequently started chemotherapy rituximab methotrexate ifosfamide intrathecal cytarabine patients symptoms gradually improved first weeks followedup autologous haematopoietic cell transplantation patient complete remission year primary tchrlbcl central nervous system immunocompetent patient extremely rare condition requires multidisciplinary approach case highlights importance undergoing sequential workup establishing treatment despite absence evidencebased guidelinespmid35135790 doi101136 bcr2021246355,0.0
differential activation mechanisms lipid gpcrs lysophosphatidic acid sphingosine 1phosphate nat commun 2022 feb 8 13 1 731 doi 101038 s41467022284172abstractlysophospholipids bioactive lipids can signal gproteincoupled receptors gpcrs best studied lysophospholipids lysophosphatidic acid lpa sphingosine 1phosphate s1p mechanisms lysophospholipid recognition active gpcr activations lysophospholipid gpcrgprotein complexes remain unclear report singleparticle cryoem structures human s1p receptor 1 s1p1 heterotrimeric gi complexes formed bound s1p multiple sclerosis ms treatment drug siponimod well human lpa receptor 1 lpa1 gi complexes presence lpa structural functional data provide insights lpa s1p adopt different conformations interact cognate gpcrs selectivity homologous lipid gpcrs s1p versus lpa different activation mechanisms gpcrs lpa s1p studies also reveal specific optimization strategies improve mstreating s1p1targeting drugspmid35136060 doi101038 s41467022284172,0.0
productivity loss among people early multiple sclerosis canadian study mult scler 2022 feb 913524585211069070 doi 101177 13524585211069070 online ahead printabstractobjectives analyze work productivity loss costs including absenteeism time missed work presenteeism reduced productivity working unpaid work loss among sample employed people multiple sclerosis pwms canada well association clinical sociodemographic workrelated factorsmethods used crosssectional data collected part canadian prospective cohort study understand progression ms canproco information valuation lost productivity questionnaireresults among 512 pwms employed 97 showed mild disability 55 experienced productivity loss due ms prior 3 months total productivity time loss 3month period averaged 60 hours sd 107 23 presenteeism 19 absenteeism 18 unpaid work leading mean cost lost productivity cad2480 sd 4282 per patient hourly paid productivity loss greater wage loss fatigue retained significant associations productivity loss outcomesconclusion unpaid work loss productivity losses exceeding employee alone due teamwork associated factors key additional contributors high economic burden ms workplace accommodations treatments targeted fatigue lessen economic impact mspmid35137613 doi101177 13524585211069070,0.0
neurotoxicityassociated sinus bradycardia chimeric antigen receptor tcell therapy hematol oncol 2022 feb 9 doi 101002 hon2976 online ahead printabstractthe advent chimeric antigen receptor car tcell therapy changed therapeutic landscape relapsed refractory aggressive bcell lymphomas cytokine release syndrome crs immune effector cellassociated neurotoxicity syndrome icans typical adverse events associated therapy cardiovascular toxicities also reported setting however scarce data regarding development sinus bradycardia car tcell therapy detail clinical course 4 patients aggressive bcell malignancies received car tcells developed transient reversible sinus bradycardia context icans also discuss several hypotheses behind pathophysiology potential new adverse eventpmid35139240 doi101002 hon2976,0.0
tumor necrosis factor systemic lupus erythematosus structure function therapeutic implications review int j mol med 2022 apr 49 4 43 doi 103892 ijmm20225098 epub 2022 feb 9abstracttumor necrosis factor tnf pleiotropic proinflammatory cytokine contributes pathophysiology several autoimmune diseases multiple sclerosis inflammatory bowel disease rheumatoid arthritis psoriatic arthritis systemic lupus erythematosus sle specific role tnf autoimmunity yet fully understood however partially complex disease sle engagement tnf receptor 1 tnfr1 tnf receptor 2 tnfr2 two variants soluble transmembrane tnf can exert multiple biological effects according different settings can either function immune regulators impacting b t dendritic cell activity modulating autoimmune response proinflammatory mediators regulating induction maintenance inflammatory processes sle present study reviews dual role tnf focusing different effects tnf may pathogenesis sle addition efficacy safety antitnf therapies preclinical clinical trials sle discussedpmid35137914 doi103892 ijmm20225098,0.0
threeyear outcome local injection autologous stromal vascular fraction cells microfat refractory perianal fistulas crohns disease abstractperianal fistulas crohns disease frequent disabling major impact patients quality life cellbased therapy using mesenchymal stem cells represents new hope patients longterm efficacy remains challenging pilot study including patients refractory complex perianal fistulas autologous adiposederived stromal vascular fraction adsvf combined microfat achieved combined remission 60 cases good safety profile 1 year purpose study assess whether results maintained longer term safety efficacy data ten patients evaluated retrospectively 3 years injection basis clinical radiological data mri analysed according magnificd score adverse event attributed experimental stemcell treatment combined remission achieved 7 patients 70 associated significant improvement magnificd mri score conclusion safety efficacy adsvf microfat injection crohns disease fistulas maintained 3 years demonstrating innovative strategy effective producing longlasting healing effect ongoing multicentre randomized placebocontrolled trial nct04010526 will helpful define place approach current therapeutic arsenal,0.0
evaluation complications associated bifocal bone transport treatment either proximal intermediate distal femoral defects caused infection outcome analysis 76 patients background purpose study evaluate outcomes bifocal bone transport treatment femoral bone defects caused infectionsmethodsclinical radiographic data patients infected femoral nonunion treated bifocal bone transport hospital analyzed retrospectively january 2008 december 2019 depending location bone defects patients divided three groups proximal intermediate distal association study application method ilizarov asami criteria applied assess bone functional outcomes postoperative complications three groups documented comparedresultsseventysix cases infected femoral bone defects 31 cases proximal 19 cases intermediate 26 cases distal managed bifocal bone transport successfully mean followup time 308 months range 23 41 months 58 men 763 18 women 236 mean age 388 years range 23 60 years bone union received 76 cases mean 69 months range 5 8 months pin tract infection observed twentynine cases 381 7 cases 92 muscle contractures 3 cases 79 joint stiffness 13 cases 171 axial deviation 2 cases 26 delayed union one case 13 nonunion none 0 transport gap refracture one patient 13 scheduled knee arthroplasty bone transport treatment endedconclusionsbone transport using external rail fixator practical method treat femoral bone defects since satisfactory rate bone union limb function recovery complications distal femoral bone transport severe proximal intermedia rate complication least three groups softtissuerelated complications likely occur intermediate bone transport,0.0
cytokine signatures differentiate systemic sclerosis patients high versus low risk pulmonary arterial hypertension background pulmonary arterial hypertension pah affects approximately 10 patients systemic sclerosis ssc leading cause death sought identify serum cytokine signatures risk stratify ssc patients potentially fatal complicationmethodssubjects high risk pah incident pah based right heart catheterization rhc enrolled multicenter prospective registry pulmonary hypertension assessment recognition outcomes scleroderma pharos lowrisk ssc patients enrolled stanford normal pulmonary function test echocardiogram parameters serum available 71 highrisk patients 81 incident pah patients 10 lowrisk patients 20 healthy controls hc custom 14 65plex arrays used cytokine analysis cytokine expression compared patient groups principal component analysis tukeys test result multiple hypotheses corrected p value 005 considered significantresultsexploratory analysis using principal components showed unique clustering patient group significant difference cytokine expression least one group comparison every cytokine overall little difference cytokine expression comparing highrisk pah patient groups however groups substantially different cytokine profiles compared lowrisk patients hcconclusionthese data suggest cytokine profiles can distinguish ssc patients highrisk pah ssc patients may lower risk pah hc however highrisk pah patients similar cytokine profiles suggesting patients disease continuum,0.0
cortical microstructure primary progressive aphasia multicenter study cortical mean diffusivity novel imaging metric sensitive early changes neurodegenerative syndromes higher cortical mean diffusivity values reflect microstructural disorganization prop,0.0
comparison tau amyloid cerebrospinal fluid biomarkers chronic traumatic encephalopathy alzheimer disease background cerebrospinal fluid csf tau betaamyloid levels chronic traumatic encephalopathy cte disease can clinically indistinguishable alzheimers disease ad largely unknown examined postmortem csf analytes among participants autopsy confirmed cte admethodsin crosssectional study 192 participants boston university ad research center vabuclf center framingham heart study fhs postmortem csf collected autopsy participants divided pathological groups based ad cte criteria 61 cte participants 18 low 43 high stage 79 ad participants 23 low 56 intermediate high 11 participants cte combined ad 41 participants lacking cte ad neuropathology meso scale discovery immunoassay system utilized measure amyloidbeta a140 a142 total tau ttau phosphorylated tau ptau181 ptau231 csf analytes compared across pathological groups cte ad control low cte low ad high cte intermediate high ad ad+cteresultsamong low disease state groups low cte group significantly higher levels ptau231 versus control group compared low ad group low cte group also found significantly lower levels a142 compared control group high cte group higher levels ptau231 lower levels a142 compared intermediate high ad groupconclusionsimportantly ptau231 a142 predictors diagnosis cte vs control cte vs ad increased csf ptau231 promising potentially sensitive biomarker cte csf a142 needs investigation cte,0.0
cannabis cannabinoids pharmacology therapeutic potential neurol neurochir pol 2022 feb 8 doi 105603 pjnnsa20220015 online ahead printabstractintroduction cannabis also known marijuana frequently used psychoactive substance world role cannabis medicine rapidly evolving advances understanding pharmacology led numerous proposed uses drugsstate art cannabis contains 9tetrahydrocannabinol cannabidiol primary constituents responsible pharmacological activity now known least two types cannabinoid receptors cb1 receptors found mainly cns primary role inhibit release neurotransmitters cb2 receptors leading role modulate cytokine release immune cell migration colocalisation cannabinoid receptors types nervous system receptors allows interact many transmitters dopamine noradrenaline acetylcholine gammaaminobutyric acid serotonin glutamic aspartic acidsclinical implications rapidly expanding understanding regarding cannabinoids led initial attempts treat selected diseases cannabinoid receptor agonists antagonists promising potential possibility treating diseases current therapy unsatisfactory neurological diseases including multiple sclerosis spastic muscular tension extrapyramidal system diseases neurodegenerative diseases cerebral ischaemia attempts treat psychiatric diseases eg psychoses neuroses mood disorders alcohol dependence syndrome cannabinoids much less advancedfuture directions cannabis cannabinoids can widely used treat several diseases alleviate symptoms efficacy specific indications always apparent exploration needed understand whether enhanced sensitivity cognitive effects 9thc depends brain cannabinoid receptor dysfunction changes contribute cognitive deterioration core pathophysiology symptoms associated schizophrenia neurological somatoform disorderspmid35133644 doi105603 pjnnsa20220015,0.0
anterior optic pathway pathology cns demyelinating diseases brain 2022 feb 3awac030 doi 101093 brain awac030 online ahead printabstractthe anterior optic pathway one preferential sites involvement cns inflammatory demyelinating diseases multiple sclerosis neuromyelitis optica optic neuritis common presenting symptom optic nerve involvement diseases often subclinical optical coherence tomography demonstrating progressive neuroretinal thinning absence optic neuritis pathological substrate findings poorly understood requires investigation access postmortem tissue samples optic nerves chiasms tracts 29 multiple sclerosis mean age 595 range 2584 years 73 samples 6 neuromyelitis optica spectrum disorders 56 1884 years 22 samples 6 acute disseminated encephalomyelitis 25 1039 years 12 samples cases 5 nonneurological controls 552 4464 years 16 samples formalinfixed paraffinembedded samples immunolabelled myelin inflammation microglial macrophage t bcells complement acute axonal injury astrocytes assessed extent distribution markers along anterior optic pathway case compartments ie parenchymal perivascular meningeal relevant demyelinated plaques classified active based established criteria multiple sclerosis demyelination present 828 cases 75 showed activity microglia macrophage lymphocyte inflammation frequently found parenchymal meningeal compartments nondemyelinated regions acute axonal injury affected 414 cases correlated extent inflammatory activity compartment even cases died advanced age 20 years disease duration anteroposterior gradient anterior optic pathway involvement observed optic nerves severely affected inflammation acute axonal injury compared optic tract higher proportion remyelinated plaques seen neuromyelitis optica spectrum disorder cases history optic neuritis extensive demyelination lost aquaporin4 reactivity contrast without prior optic neuritis demyelination rather diffuse microglial macrophage t blymphocyte inflammation parenchymal meningeal compartments acute axonal injury present 75 cases acute demyelinating encephalomyelitis featured intense inflammation perivenular demyelination 33 cases findings suggest chronic inflammation frequent leads neurodegeneration multiple sclerosis neuromyelitis optica regardless disease stage chronic inflammation subsequent neurodegeneration occurring along optic pathway broadens plaquecentred view diseases partly explains progressive neuroretinal changes observed optic coherence tomography studiespmid35134111 doi101093 brain awac030,1.0
interleukin 32 gene promoter polymorphism genetic risk factor multiple sclerosis kashmiri population gene 2022 feb 4146261 doi 101016 jgene2022146261 online ahead printabstractobjective although exact cause multiple sclerosis known number environmental genetic risk factors present study done determine association il32 gene promoter polymorphism il32 levels multiple sclerosismethods 48 relapsing remitting multiple sclerosis patients 60 healthy controls compared il32 gene promoter polymorphism il32 levelsresults significant difference genotype ct ms patients healthy controls p 0130 significant difference genotype cc frequencies among ms patients healthy controls p 0039 difference c allele frequency also statistically significant two study groups p 001 multivariate regression analysis revealed cc genotype might impact risk disease susceptibility 371 times presence c allele might increase risk susceptibility multiple sclerosis 226 fold serum il32 levels statistically different multiple sclerosis patients healthy controls wild mutant genotypesconclusions il32 gene promoter polymorphism genetic risk factor multiple sclerosis patients particularly womenpmid35131367 doi101016 jgene2022146261,0.0
economic burden multiple sclerosis georgia georgian med news 2022 jan 322 167170abstractthe purpose study estimate economic burden multiple sclerosis georgia compare costs patients different course disease disability level hospitalbased cohort study conducted psarajishvili institute neurology medical center pineo estimate direct medical costs patients ms treated 20192020 mean annual direct medical cost ms patient diseasemodifying therapies dmts statistically higher nondmts patient estimated 232547lari 73825 sd 90263 cis211337253758 versus 14291lari 4536 sd 8617 cis 1309515486 p00001 ms places huge economic burden healthcare model society georgia dmts main driver costpmid35134781,0.0
strong evidence epsteinbarr virus infection triggers multiple sclerosis nat neurosci 2022 feb 7 doi 101038 s41593022010175 online ahead printno abstractpmid35132232 doi101038 s41593022010175,0.0
pregnancy management multiple sclerosis demyelinating diseases continuum minneap minn 2022 feb 1 28 1 1233 doi 101212 con0000000000001108abstractpurpose review multiple sclerosis ms neuromyelitis optica spectrum disorders nmosds chronic autoimmune demyelinating conditions central nervous system often diagnosed women childbearing age therefore safe family planning pregnancy postpartum management important considerations many patients ms nmosdrecent findings many patients ms can safely become pregnant remain well throughout pregnancy postpartum period guidance specialists treatment planning pregnancy women nmosd may face increased risk neurologic obstetric complications recent attention focused evaluating safety pharmacologic agents pregnancy breastfeeding unfortunately care disparities remain common ms nmosd recovery function often optimally managed postpartum periodsummary article reviews current state knowledge peripartum management neurologic conditions offers practical considerations case studies caring women ms nmosd childbearing potential treatment planning important optimize outcomes patient newbornpmid35133309 doi101212 con0000000000001108,1.0
randomized controlled trial webbased mindfulness programme people ms without history recurrent depression mult scler 2022 feb 713524585211068002 doi 101177 13524585211068002 online ahead printabstractbackground evidence shows small positive effects associated psychological treatments people multiple sclerosis pwms recent metaanalysis treatment largest effect size mindfulnessbased intervention mbi objectives aimed determine whether internetdelivered mbi beneficial pwms furthermore aimed investigate history recurrent depression moderator treatment outcomemethods participants n 132 assessed based whether history recurrent depression stratified randomized mbi waitlist outcomes assessed baseline postintervention 3 6 monthsresults mbi group reported significantly improved depressive symptoms primary outcome compared waitlist p 0046 cohens d 039 history recurrent depression benefitted significantly without p 0034 d 066 benefits healthrelated quality life hrqol mbi irrespective depression history p 0009 d 05 pain interference less overall mbi group p 0001 d 02 change time differ waitlist treatment effects anxiety pain severity fatigueconclusion internetdelivered mbi significantly improved depressive symptoms hrqol pwms depression benefits greater history recurrent depressiontrial registration actrn12618001260213 available https wwwanzctrorgau trial registration trialreviewaspxid375598pmid35130768 doi101177 13524585211068002,0.0
cerebrospinal fluid kappa free light chains biomarker multiple sclerosisfrom diagnosis prediction disease activity wien med wochenschr 2022 feb 8 doi 101007 s10354022009127 online ahead printabstractmultiple sclerosis ms chronic immunemediated disorder central nervous system shows high interindividual heterogeneity frequently poses challenges regarding diagnosis prediction disease activity context evidence intrathecal inflammation provides important information might captured kappa free light chains flc cerebrospinal fluid csf review provide overview currently known flc historical development available assays current evidence diagnostic prognostic value ms briefly intrathecal flc synthesis reaches similar diagnostic accuracy compared wellestablished csfrestricted oligoclonal bands ocb identify patients ms recent studies even depict value prediction early ms disease activity furthermore detection flc significant methodological advantages comparison ocb detectionpmid35133530 doi101007 s10354022009127,0.0
serum neurofilament light multiple sclerosis progression independent acute inflammation jama netw open 2022 feb 1 5 2 e2147588 doi 101001 jamanetworkopen202147588no abstractpmid35133438 doi101001 jamanetworkopen202147588,0.0
impaired nuclear transport induced juvenile als causing p525l mutation nls domain fus molecular mechanistic study biochim biophys acta proteins proteom 2022 feb 5140766 doi 101016 jbbapap2022140766 online ahead printabstractamyotrophic lateral sclerosis als frontotemporal lobar degeneration ftld progressive neurological disorders affecting motor neurons cellular aggregates fused sarcoma fus protein found cytoplasm als ftld patients nuclear localisation signal nls domain fus binds karyopherin 2 kap2 drives nuclear transport fus cytoplasm several pathogenic mutations reported fus nls associated impaired nuclear transport cytoplasmic mislocalisation p525l mutation nls commonly found cases juvenile als jals affects individuals 25 years age jals progresses aggressively causing death within year onset study elucidates molecular mechanism behind jalscausing p525l mutation hindering nuclear transport fus perform multiple molecular dynamics simulations aqueous hydrophobic solvent understand effect mutation molecular level dynamics kap2fus complex better captured hydrophobic solvent compared aqueous solvent p525 y526 pymotif nls exhibit finetuned stereochemical arrangement essential optimum kap2 binding p525l causes loss several native contacts interface leading weaker binding promotes selfaggregation fus cytoplasm native complex samples closed conformation mutant complex exhibits open conformation exposing hydrophilic residues kap2 hydrophobic solvent mutant complex also fails exhibit springlike motion essential transport nuclear pore complex study provides mechanistic insight binding affinity nls kap2 inhibits selfaggregation fus preventing disease conditionpmid35134572 doi101016 jbbapap2022140766,0.0
epsteinbarr virus multiple sclerosis nat rev neurosci 2022 feb 7 doi 101038 s41583022005669 online ahead printno abstractpmid35132220 doi101038 s41583022005669,0.0
effects actual imagined musiccued gait training motor functioning brain activity people multiple sclerosis protocol randomised parallel multicentre trial bmj open 2022 feb 7 12 2 e056666 doi 101136 bmjopen2021056666abstractintroduction motor imagery mi refers mental rehearsal physical action without muscular activity previous studies showed mi combined rhythmicauditory cues improved walking fatigue quality life qol people multiple sclerosis pwms largest improvements seen music verbally cued mi unclear whether actual cued gait training achieves similar effects walking cued mi pwms furthermore pwms unknown whether interventions leads changes brain activation purpose study therefore compare effects imagined actual cued gait training combination thereof walking brain activation patterns fatigue cognitive emotional functioning pwmsmethods analysis prospective doubleblind randomised parallel multicentre trial will conducted 132 pwms mild moderate disability randomised three groups participants will receive music metronome verbal cueing plus mi walking 1 mi combined actual gait training 2 actual gait training 3 30 min 4 per week 4 weeks supported weekly phone calls participants will practise home guided recorded instructions primary endpoints will walking speed timed 25foot walk distance 2 min walk test secondary endpoints will brain activation patterns fatigue qol mi ability anxiety depression cognitive functioning musicinduced motivationtomove pleasure arousal selfefficacy data will collected baseline postintervention 3month followup mri reference values will generated using 15 matched healthy controlsethics dissemination study follows standard protocol items recommendations interventional trialspro extension ethical approval received ethics committees medical universities innsbruck 1347 2020 graz 33056 ex 20 21 austria results will disseminated via national international conferences published peerreviewed journalstrial registration number drks00023978pmid35131834 doi101136 bmjopen2021056666,0.0
association neurodegeneration local complement activation thalamus progressive multiple sclerosis outcome brain pathol 2022 feb 7e13054 doi 101111 bpa13054 online ahead printabstractthe extent grey matter demyelination neurodegeneration progressive multiple sclerosis pms brains postmortem associates severe disease regional tissue atrophy especially affecting cortical deep grey matter including thalamus prognostic poor outcomes microglial complement activation important pathogenesis contribute damaging processes underlie tissue atrophy pms investigated extent pathology innate immune activation thalamus comparison cortical grey white matter blocks 21 cases pms 10 matched controls using digital pathology workflow show thalamus invariably affected demyelination far higher proportion active inflammatory lesions forebrain cortical tissue blocks cases lesions larger frequent medial nuclei near ventricular margin whilst neuronal loss greatest lateral thalamic nuclei extent thalamic neuron loss associated thalamic demyelination correlated burden white matter pathology forebrain areas spearman r 079 p 00001 thalamic neuronal loss seen forebrain cortical areas correlated disease duration spearman r 058 p 0009 age death spearman r 047 p 0045 immunoreactivity complement pattern recognition molecule c1q products complement activation c4d bb c3b elevated thalamic lesions active inflammatory pathology complement regulatory protein c1 inhibitor unchanged expression conclude active inflammatory demyelination neuronal loss local complement synthesis activation thalamus important pathological clinical disease outcomes pmspmid35132719 doi101111 bpa13054,1.0
distribution relation two arm function tests box blocks test nine hole peg test across disease severity levels types multiple sclerosis abstractbackgroundregular upper limb evaluation persons multiple sclerosis detect early alterations monitor possible deterioration gross fine motor dexterity important optimal levels participation life activities across life span purpose present study inquire upon alterations bilateral gross fine manual dexterity measured box block test bbt nine hole peg test nhpt persons ms pwms across wide range disability levels across ms typesmethodsthis secondary crosssectional analysis bbt nhpt administered 215 pwms disability levels three ms phenotypes relapsingremitting primary progressive secondary progressive rrms ppms spms inquire prevalence alterations upper limb gross fine dexterity pwms test scores compared normative healthy subjectsnull values abnormal values defined scores equal exceeding 2 standard deviations normative values nhpt bbt data arms analyzed disability level type ms characterization comparisons based disability level sample divided four groups according edss score 035 categorized mild edssmi edss35 55 categorized moderate edssmo edss55 65 categorized severe edssse disability levels 7 beyond categorized severenonambulant edsssen finally correlations ul dexterity measures bilaterally carried outresultsmean sd age sample 5407 1281 years mean sd disease duration 1891 1095 years median edss iqr 65 55 7 fiftythree rrms 19 ppms 28 spms almost whole sample 962 showed abnormal scores bbt 915 abnormal bilateral scores abnormal scores present nhpt 854 whole sample 689 bilateral abnormal scores increase disability levels mean number blocks moved reduced time taken finish nhpt increased bbt nhpt arm highly correlated disability levels correlation ranging 074 086overall right left arm statistical differences median scores nhpt peg sec p0004 similar scores bbt p057 abnormal bilateral scores recorded 85 pwrr 96 pwsp 100 pwpp bbt 56 pwrr increasing 80 85 pwpp pwsp progressive forms ms presented statistically different values bbt p0001 nhpt respect rrms type p0001 conclusionwe found fine gross manual dexterity altered respect normative values persons ms abnormalities gross manual dexterity prevalent pronounced earlier disease course similarly regard ms types bilateral alterations gross manual dexterity prevalent fine manual dexterity three phenotypes considered,0.0
posttranslational modifications proteins key features identification csf biomarkers multiple sclerosis background multiple sclerosis inflammatory degenerative disease central nervous system cns characterized demyelination concomitant axonal loss lack single specific test similarity inflammatory diseases central nervous system makes difficult clear diagnosis multiple sclerosis therefore laboratory tests allows clear definite diagnosis well predict different clinical courses disease utmost importance herein compared cerebrospinal fluid csf proteome patients multiple sclerosis relapseremitting phase disease diseases cns inflammatory noninflammatory aiming identifying reliable biomarkers multiple sclerosismethodscsf samples discovery group resolved 2dgel electrophoresis followed identification protein spots mass spectrometry results analyzed using univariate students t test multivariate hierarchical cluster analysis principal component analysis linear discriminant analysis statistical numerical techniques identify set protein spots differentially expressed csf samples patients multiple sclerosis compared two groups validation results performed samples different set patients using quantitative eg elisa semiquantitative eg western blot experimental approachesresultsanalysis 2dgels showed 13 protein spots differentially expressed three groups patients alpha1antichymotrypsin prostaglandinh2isomerase retinol binding protein 4 transthyretin ttr apolipoprotein e gelsolin angiotensinogen agrin serum albumin myosin15 apolipoprotein b100 efhand calciumbinding domaincontaining protein elisa experiments allowed validating part results obtained proteomics analysis showed alterations csf proteome also mirrored serum samples multiple sclerosis patients csf multiple sclerosis patients characterized ttr oligomerization thus highlighting importance analyzing posttranslational modifications proteome identification novel biomarkers diseaseconclusionsthe model built based results obtained upon analysis 2dgels validation phase attained accuracy 80 distinguishing multiple sclerosis patients two groups,1.0
development convolutional neural network identification measurement median nerve ultrasound images acquired carpal tunnel level background deep learning applied ultrasound us can provide feedback sonographer correct identification scanned tissues allows faster standardized measurements frequently adopted parameter us diagnosis carpal tunnel syndrome increasing crosssectional area csa median nerve aim develop deep learning algorithm relying convolutional neural networks cnns localization segmentation median nerve automatic measurement csa us images acquired proximal inlet carpal tunnelmethodsconsecutive patients rheumatic musculoskeletal disorders recruited transverse us images acquired carpal tunnel inlet csa manually measured anatomical variants registered dataset consisted 246 images 157 training 40 validation 49 testing 103 patients associated manual annotations nerve boundary mask rcnn stateoftheart cnn image semantic segmentation trained dataset accurately localize segment median nerve section evaluate performances testing set precision prec recall rec mean average precision map dice similarity coefficient dsc computed subanalysis excluding anatomical variants performed csa automatically measured algorithmresultsthe algorithm correctly identified median nerve 41 49 images 837 41 43 images 953 excluding anatomical variants following metrics obtained without anatomical variants respectively prec 086 033 096 018 rec 088 033 098 015 map 088 033 098 015 dsc 086 019 088 019 agreement algorithm sonographer csa measurements excellent icc 097 094098 conclusionsthe developed algorithm shown excellent performances especially excluding anatomical variants future research aim expanding us image dataset including wider spectrum normal anatomy pathology deep learning approach shown high potentiality fully automatic support us assessment carpal tunnel syndrome,0.0
incidence cancer patients multiple sclerosis ms treated fingolimod systematic review metaanalysis abstractbackground fingolimod sphingosine1phosphatereceptor modulator used relapsing form ms controversial reports regarding incidence cancer patients ms treated fingolimod therefore designed systematic review metaanalysis estimate pooled incidence cancer patients ms treated various dose fingolimodmethod two expert researchers searched systematically pubmed scopus embase web science google scholar well references included studies conference abstracts published november 2021results found 5231 articles literature search deleting duplicates 3070 remained thirtyfour articles remained metaanalysis totally 64135 patients ms received fingolimod enrolled total number patients cancer 2561 pooled incidence cancer patients ms received fingolimod 202 95 ci200301 i2978 p0001 pooled incidence cancer group received 05 mg 201 95ci100204 i2917 p0001 pooled incidence cancer group received 125 mg 301 95ci202501 i2675 p0001 conclusion result systematic review metaanalysis shows pooled prevalence cancer ms patients received fingolimod 2 risk cancer higher patients ms received 125 mg fingolimod 125 mg cases received 05 mg,0.0
s1p receptor modulators multiple sclerosis detecting potential skin cancer safety signal abstractintroductions1p receptor modulators oral diseasemodifying therapies dmts multiple sclerosis associated cases basal cell carcinoma clinical trials study aims investigating realworld adverse event reporting system whether s1p receptor modulators increase risk skin cancer reporting compared dmtsmethodsadverse event reports fda adverse event reporting system faers extracted cleaned analyzed 2004q1 2020q4 crude adjusted reported odds ratios cror aror outcomes basal cell carcinoma squamous cell carcinoma melanoma calculated dmts sensitivity analysis looked outcome separatelyresultsthe aror 95ci siponimod 968 5481579 fingolimod 454 386532 indicating safety signal s1p receptor modulators skin cancer ozanimod 52 complete reports without cases sensitivity analysis siponimod showed signal basal cell carcinoma 2283 12273883 fingolimod outcomes separately including melanoma 302 231389 notably among dmts alemtuzumab 440 298625 cladribine 328 117713 presented also signal disproportionate reporting ocrelizumab showed signal sensitivity analysis melanoma 255 121465 conclusionss1p receptors seem increase skin cancer reporting faers association strongest basal cell carcinomas therefore close dermatologic surveillance therapy needed whether fingolimod ocrelizumab also increase risk melanoma needs investigation,0.0
humoral cellular immunity convalescent vaccinated covid19 people multiple sclerosis effects disease modifying therapies abstractobjectives determine antisarscov2 antibodies tcell immunity convalescent people multiple sclerosis pwms pwms vaccinated covid19 depending disease modifying therapy comparison healthy controls hc methods 75 participants enrolled group 129 387 covid19 convalescent participants group 234 453 covid19 vaccinated group 312 160 covid19 convalescent participants later vaccinated covid19 cellular immunity evaluated determination number cd4+ cd8+ cells secreting tnf ifn il2 stimulation sarscov2 peptidesresults pwms treated ocrelizumab less likely develop humoral immunity covid19 recovery vaccination difference observed cellular immunity studied parameters pwms treated ocrelizumab compared hc pwms treatment nave first line therapies findings consistent convalescent vaccinated convalescent+vaccinated participants covid19 vaccinated convalescent pwms ocrelizumab compared covid19 convalescent hc vaccinated show statistically difference rate seroconversion titers sarscov2 antibodiesconclusion presence cellular immunity pwms bcell depleting therapies reassuring least partial protection severe covid19 outcomes can expected,0.0
cns endothelial derived extracellular vesicles biomarkers active disease multiple sclerosis background multiple sclerosis ms complex heterogenous disease characterized inflammation demyelination bloodbrain barrier bbb permeability currently active disease determined physician confirmed relapse detection contrast enhancing lesions via mri indicative bbb permeability however clinical confirmation active disease can cumbersome disease monitoring ms benefit identification easily accessible biomarker active disease believe extracellular vesicles ev isolated plasma excellent candidates fulfill need critical role bbb permeability plays ms pathogenesis identification active disease sought identify ev originating central nervous system cns endothelial biomarkers active ms endothelial cells secrete ev stimulated injured hypothesized circulating concentrations cns endothelial derived ev will increased ms patients active diseasemethodsto test developed novel method identify ev originating cns endothelial cells isolated patient plasma using flow cytometry endothelial derived ev identified absence lymphocyte platelet markers cd3 cd41 respectively positive expression panendothelial markers cd31 cd105 cd144 determine endothelial derived ev originated cns endothelial cells ev expressing cd31 cd105 cd144 evaluated expression myelin lymphocyte protein mal protein specifically expressed cns endothelial cells compared endothelial cells peripheral organsresultsquality control experiments indicate ev detected using flow cytometry method 02 1 micron size flow cytometry analysis ev isolated 20 healthy controls 16 relapsingremitting ms rrms patients active disease receiving disease modifying therapy 14 rrms patients stable disease receiving disease modifying therapy 17 relapsingrrms patients stable disease receiving natalizumab 14 rrms patients stable disease receiving ocrelizumab revealed significant increase plasma concentration cns endothelial derived ev patients active disease compared groups p 0001 conclusions first time identified method identify cns endothelial derived ev circulation human blood samples results pilot study indicate increased levels cns endothelial derived ev may biomarker bbb permeability active disease ms,1.0
incidence malignant neoplasms mortality people affected multiple sclerosis epoch diseasemodifying treatments populationbased study tuscan residents abstractbackgroundconflicting data currently available risk malignancies people affected multiple sclerosis pwms potential relative contribution risk diseasemodifying therapies dmts still debated moreover data longterm prognosis pwms mostly derive natural history studies updated observations treatment era lackingmethodsincidence cancer mortality analysed pwms cohort residents tuscany 17year period observation treatment era compared rates observed 110 sex agematched control population resident geographical arearesultssixhundred sixtyone pwms included median age 43 years range 19 80 87 affected relapsingremitting ms sixtyeight percent cases exposed dmts study period age sex standardized incidence malignancy differ groups 391000 95 confidence interval ci 375 415 personyears 411000 95 ci 376 442 personyears ms control cohorts respectively frequent cancers reported pwms breast gastrointestinal gynaecological cancers standardized mortality rates 201000 personyears 95 ci 158 237 241000 95 ci 203 278 personyears ms control cohorts respectively differ groups also excluding traumatic causeofdeath 16 vs 17 conclusionsthe incidence cancer mortality differ pwms general population residing geographical area suggesting life expectancy pwms improved treatment era,0.0
tlr#x2f cd44 axis regulates t cell trafficking experimental human multiple sclerosis iscience 2022 jan 11 25 2 103763 doi 101016 jisci2022103763 ecollection 2022 feb 18abstractin pathogenesis autoimmune disorders modulation leukocytes trafficking plays central role still poorly understood focused effect tlr2 ligands trafficking t helper cells reshuffling cd44 isoforms repertoire concurrently strain background tlr2 haplotype affected wnt catenin signaling pathway expression splicing factors eae mcd44 v9 v 10 specifically enriched forebrain showed increased ability bind stably osteopontin similarly observed hcd44 v7 highly enriched cells cerebrospinal fluid ms patients active lesions moreover tlrs engagement modulated composition cd44 variants also human t helper cells supporting hypothesis pathogens commensals tlrs turn modulate repertoire cd44 isoforms thereby controlling distribution lesions cns interference mechanism s represents potential tool prevention treatment autoimmune relapses exacerbationspmid35128357 pmcpmc8804271 doi101016 jisci2022103763,0.0
comparison susceptibility weighted imaging conventional mri sequences multiple sclerosis plaque assessment crosssectional study j res med sci 2021 dec 22 26128 doi 104103 jrmsjrms_726_17 ecollection 2021abstractbackground current study performed compare susceptibilityweighted imaging swi magnetic resonance imaging mri methods t2weighted t2w fluidattenuated inversion recovery flair imaging multiple sclerosis ms plaque assessmentmaterials methods crosssectional study conducted among 50 ms patients referred shafa imaging center isfahan iran patients fulfilled mcdonald criteria diagnosed ms professional neurologist least 1 year study initiation included study eligible patients underwent brain scans using swi t2w imaging flair plaques number volume detected separately imaging sequence moreover identified lesions swi sequence evaluated terms iron deposition central veinsresults totally 50 patients 10 males 40 females mean age 2848 525 years included current study majority patients 60 disease duration 5 years mean expanded disability status score 256 132 significant difference different imaging modalities terms plaques number volume p 005 also found high correlation swi conventional imaging techniques t2w r 097 091 p 0001 flair r 099 099 p 0001 estimation number volume plaques p 0001 conclusion results present study indicated swi conventional mri sequences similar efficiency plaque assessment ms patientspmid35126591 pmcpmc8772512 doi104103 jrmsjrms_726_17,0.0
healthrelated quality life children multiple sclerosis mediated healthrelated quality life parents mult scler 2022 feb 713524585211061521 doi 101177 13524585211061521 online ahead printabstractbackground previously found children chronic disease multiple sclerosis ms reported lower healthrelated quality life hrqol compared children experienced transient illness termed monophasic acquired demyelinating syndromes monoads parents children ms also reported lower hrqolobjectives evaluated whether parental hrqol mediated relationship diagnosis ms hrqol affected children ascertain effect ms diagnosis compared children ms monoadsmethods children enrolled prospective multisite canadian study random effects models evaluated whether parental hrqol mediated relationship diagnosis ms hrqol affected children adjusting child family characteristicsresults 207 parentchild dyads 65 ms 142 monoads completed hrqol questionnaires modeled childs hrqol adjusting covariates parents hrqol diagnosis ms associated lower hrqol child p 0004 added parental hrqol model association diagnosis ms childs hrqol diminished p 013 conclusions parental hrqol mediated relationship diagnosis ms hrqol affected children emphasizing importance familycentered carepmid35130081 doi101177 13524585211061521,1.0
effects noninvasive brain stimulation multiple sclerosis systematic review metaanalysis ther adv chronic dis 2022 feb 2 1320406223211069198 doi 101177 20406223211069198 ecollection 2022abstractobjective objective metaanalysis summarize evidence therapeutic effects noninvasive brain stimulation nibs core symptoms multiple sclerosis ms specifically findings studies deploying transcranial direct current stimulation tdcs repetitive transcranial magnetic stimulation rtms protocols summarized reviewmethods systematically searched articles published four databases 31 may 2021 compared effects active tdcs rtms sham intervention ms patients used randomeffects model metaanalysis metaregression subgroup metaanalysis used examine effects stimulation dose different stimulation protocols respectivelyresults twentyfive randomized controlled trials rcts included review consisting 19 tdcs 6 rtms studies tdcs led significant immediate reduction fatigue large effect size hedgess g 0870 95 confidence intervals ci 1225 0458 number needed treat nnt 2 particularly subgroup analysis showed applying tdcs left dlpfc bilateral s1 led fatigue reductions compared sham stimulation furthermore tdcs favorable effects fatigue ms patients low physical disability high physical disability additionally improved cognitive function finally whereas rtms observed reduce muscle spasticity nibs protocols showed effect msassociated pain mood symptomsconclusion tdcs ms alleviates fatigue improves cognitive function whereas rtms reduces muscle spasticity highquality studies needed substantiate therapeutic effects different nibs protocols mspmid35126965 pmcpmc8814979 doi101177 20406223211069198,0.0
alu rna structural features modulate immune cell activation atoi editing alu rnas diminished human inflammatory bowel disease front immunol 2022 jan 20 13818023 doi 103389 fimmu2022818023 ecollection 2022abstractalu retrotransposons belong class short interspersed nuclear elements sines alu rna abundant cells repetitive structure forms doublestranded rnas dsrna activate dsrna sensors trigger innate immune responses significant pathological consequences mechanisms prevent innate immune activation include deamination adenosines inosines dsrnas referred atoi editing degradation alu rnas endoribonucleases sequestration alu rnas rna binding proteins previously demonstrated widespread loss alu rna atoi editing associated diverse human diseases including viral covid19 influenza autoimmune diseases multiple sclerosis demonstrate loss atoi editing leukocytes also associated inflammatory bowel diseases structurefunction analysis demonstrates ability activate innate immune responses resides left arm alu rna requires 5ppp rigi major alu dsrna sensor atoi editing disrupts structure function edited alu rnas inhibit activity unedited alu rnas altering alu rna nucleotide sequence increases biological activity two classes alu rnas exist one class stimulates irf nfkb transcriptional activity second class stimulates irf transcriptional activity thus alu rnas play important roles human disease may also therapeutic potentialpmid35126398 pmcpmc8813004 doi103389 fimmu2022818023,0.0
components endocannabinoid system effects cannabinoids bone diseases minireview front pharmacol 2022 jan 19 12793750 doi 103389 fphar2021793750 ecollection 2021abstractbackground endocannabinoid system ecs involved multiple physiological processes including appetite regulation pain perception motor function development immune response regulation cannabinoids approved clinical treatment nausea vomiting caused cytostatic therapy cancer chemotherapy loss appetite hiv aidsassociated cachexia refractory spasms induced multiple sclerosis chronic pain urinary incontinence methods check research ecs bone diseases past 20 years results many studies demonstrated endocannabinoids ecbs cannabinoid receptors cbrs expressed bone synovial tissues playing important roles bone metabolism preclinical studies using cannabisbased therapies animal models shown cannabinoids cbs can alleviate development osteoarthritis oa prevent osteoporosis op reduce cancerinduced osteolytic destruction improve fracture healing highlighting therapeutic potential cbs human bone diseases conclusions present review summarizes various components ecs bone diseases potential therapeutic targetpmid35126132 pmcpmc8815309 doi103389 fphar2021793750,0.0
safety efficacy mesenchymal stromal cells cellular therapeutics rheumatic diseases 2022 review know far arthritis rheumatol 2022 feb 6 doi 101002 art42081 online ahead printabstractalthough number new immunosuppressives biologics approved treating various autoimmune inflammatory rheumatic diseases remain substantial number patients clinical response limited clinical response available treatments use cellular therapies novel approach treatment autoimmune inflammatory rheumatic diseases perhaps enhanced efficacy less toxicity current therapies autologous hematopoietic stem cell transplants first foray cellular therapies proven efficacy scleroderma multiple sclerosis newer yet unproven cellular therapies include allogenic mesenchymal stromal cells shown effective graft vs host disease healing crohns fistulas cart cells effective various malignancies possible usage rheumatic diseases shown preclinical studies murine lupus recently human lupus t regulatory cells one master controllers immune response decreased number effectiveness specific autoimmune diseases expansion autologous t regulatory cells attractive approach controlling autoimmunity number regulatory cells immune system including regulatory b cells dendritic cells macrophages t cell types early development review current evidence efficacy mechanisms actions cellular therapies already use clinical trials human autoimmune diseases will discussed including limitations therapies potential side effectspmid35128813 doi101002 art42081,0.0
effect aromatherapy lavender essential oil working memory women multiple sclerosis j med life 2021 novdec 14 6 776781 doi 1025122 jml20200115abstractworking memory one cognitive components may impaired patients multiple sclerosis accordingly study aims determine effects aromatherapy lavender essential oil working memory women multiple sclerosis ms clinical trial 60 women multiple sclerosis selected using sampling method patients referred ms clinic rafsanjan based inclusion exclusion criteria participants randomly divided intervention placebo groups addition working memory test developed daneman carpenter used evaluate participants working memory intervention day last intervention collected data analyzed using spss statistics version 180 according intragroup comparison results based paired ttest mean score working memory intervention intervention group 8277687 increased 8764557 intervention p0001 average working memory score placebo group 80301109 82091131 intervention respectively statistically significant difference p0154 based findings independent ttest mean scores working memory statistically significant difference intervention placebo groups intervention p002 according results study aromatherapy lavender essential oil improved working memory women multiple sclerosispmid35126747 pmcpmc8811666 doi1025122 jml20200115,0.0
cytoprotective gastric pentadecapeptide bpc 157 resolves major vessel occlusion disturbances ischemiareperfusion injury following pringle maneuver buddchiari syndrome world j gastroenterol 2022 jan 7 28 1 2346 doi 103748 wjgv28i123abstractthe stable gastric pentadecapeptide bpc 157 counteracts various venous occlusioninduced syndromes summarized arguments roberts cytoprotection concept substantiate resolution different major vessel occlusion disturbances particular ischemiareperfusion injury following pringle maneuver buddchiari syndrome obtained bpc 157 therapy conceptually new point namely endothelium maintenance epithelium maintenance recruitment collateral blood vessels compensate vessel occlusion reestablish blood flow bypass occluded ruptured vessel paper summarize evidence native cytoprotective gastric pentadecapeptide bpc 157 stable human gastric juice membrane stabilizer counteracts gutleaky syndrome particular target distinctive standard peptide growth factors involving particular molecular pathways controlling vegf pathways early 1990s bpc 157 appeared late outbreak roberts szabos cytoprotectionorganoprotection concept like previous theoretical practical breakthrough 1980s braingut axis gutbrain axis time went reported effects likely useful theory practical implementation justification meantime several reviews suggest bpc 157 lethal dose profound cytoprotective activity used demonstrated ulcerative colitis multiple sclerosis trials likely may bring theory practical application starting initial argument degradation human gastric juice 24 h thereby therapeutic effectiveness including via therapeutic peroral regimen pleiotropic beneficial effectspmid35125818 pmcpmc8793015 doi103748 wjgv28i123,0.0
longterm suppression circulating proinflammatory cytokines multiple sclerosis patients following autologous haematopoietic stem cell transplantation front immunol 2022 jan 19 12782935 doi 103389 fimmu2021782935 ecollection 2021abstractautologous haematopoietic stem cell transplantation ahsct therapeutic option haematological malignancies nonhodgkins lymphoma nhl recently autoimmune diseases treatmentrefractory multiple sclerosis ms immunological mechanisms underlying remission ms patients following ahsct likely involve antiinflammatory shift milieu circulating cytokines hypothesised immunological tolerance ms patients postahsct reflected increase antiinflammatory cytokines suppression proinflammatory cytokines patient blood investigated hypothesis using multiplexelisa assay compare concentrations secreted cytokine peripheral blood ms patients nhl patients undergoing ahsct ms patients detected significant reductions proinflammatory t helper th 17 cytokines interleukin il 17 il23 il1 il21 th1 cytokines interferon ifn il12p70 ms patients day 8 24 months postahsct changes observed nhl patients despite similar preconditioning treatment ahsct proinflammatory cytokines show similar trends cohorts il8 tumour necrosis factor tnf indicating probable treatmentrelated ahsct response antiinflammatory cytokines il10 il4 il2 transiently reduced postahsct il10 exhibiting significant surge day 14 postahsct ms patients relapsed postahsct exhibited significantly elevated levels il17 12 months postahsct unlike nonrelapse patients displayed sustained suppression th17 cytokines postahsct timepoints 24 months findings suggest suppression th17 cytokines essential induction longterm remission ms patients following ahsctpmid35126353 pmcpmc8807525 doi103389 fimmu2021782935,0.0
constructing multiple sclerosis diagnosis model based microarray front neurol 2022 jan 20 12721788 doi 103389 fneur2021721788 ecollection 2021abstractintroduction multiple sclerosis immunemediated demyelinating disorder central nervous system complexity etiology pathology clinical manifestations diversity classification diagnosis ms difficult found mcdonald criteria strict relies heavily evidence dis dit therefore hope find new method supplement evidence improve accuracy ms diagnosisresults finally selected gse61240 gse18781 gse185047 based gpl570 platform build diagnosis model initially selected 54 ms susceptibility locus genes identified imsgc wtccc2 predictors model random forests series screening logistic regression model established 4 genes final predictors external validation model showed high accuracy auc 096 accuracy 8630 finally established nomogram online prediction tool better display diagnosis modelconclusion diagnosis model based microarray data study high degree discrimination calibration validation set helpful diagnosis absence evidence dis dit one sle case misdiagnosed ms indicating model high specificity 9393 useful differential diagnosis significance study lies proving feasible identify ms peripheral blood rna application model used supplement mcdonald criteria still need trained larger sample sizepmid35126277 pmcpmc8812326 doi103389 fneur2021721788,1.0
nextgeneration sequencing whole mitochondrial genome identifies functionally deleterious mutations patients multiple sclerosis plos one 2022 feb 7 17 2 e0263606 doi 101371 journalpone0263606 ecollection 2022abstractmultiple sclerosis ms immunemediated disease central nervous system genetics environmental determinants studies focused neurogenetics ms showed mitochondrial dna mtdna mutations can ultimately lead mitochondrial dysfunction alter brain energy metabolism cause neurodegeneration analyzed whole mitochondrial genome using nextgeneration sequencing ngs 47 saudi individuals 23 patients relapsingremitting ms 24 healthy controls identify mtdna diseaserelated mutations variants large number variants detected dloop coding genes mtdna distinct unique variants present patients occur controls number common variants shared among two groups prevalence common variants differed significantly patients controls thus implicated susceptibility ms unique variants present patients 34 missense mutations located different mtdnaencoded genes seven mutations previously reported ms predicted deleterious considerable impacts functions structures encodedproteins may play role pathogenesis ms include two heteroplasmic mutations namely 10237tc mtnd3 gene 15884gc mtcyb gene three homoplasmic mutations namely 9288ag mtco3 gene 14484tc mtnd6 gene 15431ga mtcyb gene 8490tc mtatp8 gene 5437ct mtnd2 gene notably patients harboured multiple mutations patients carried mutations study first sequence entire mitochondrial genome ms patients arab population results expanded mutational spectrum mtdna variants ms highlighted efficiency ngs populationspecific mtdna variant discovery investigations larger cohort warranted confirm role mtdna mspmid35130313 doi101371 journalpone0263606,0.0
evaluation expressed mir129 mir549a patients multiple sclerosis adv biomed res 2021 dec 25 1048 doi 104103 abrabr_268_20 ecollection 2021abstractbackground expression micrornas mirnas circulating biomarkers underlined multiple sclerosis ms last decade due presence possible relationship expressed mirnas heterogeneous appearances pathological processes ms present study attempts evaluate expression mir129 mir549a patients ms comparison healthy control hc groupmaterials methods peripheral blood mononuclear cells separated fifty patients ms subtypes including relapsingremitting ms secondary progressive ms kashani hospital isfahan iran fifty people hc group rna extraction complementary dna synthesis expression mir129 mir549a evaluated patients ms comparison hc group using quantitative realtime polymerase chain reaction assay data analyzed using kolmogorovsmirnov mannwhitney tests spearmans correlation coefficient used examine relationship mir129 mir549a ageresults results showed expression mir129 mir549a significant patients ms comparison hc group furthermore relationship mirnas age gender significantconclusion suggest expression mir129 mir549a circulating mirnas peripheral blood mononuclear cells considered biomarker diagnosis para clinicalpmid35127575 pmcpmc8781915 doi104103 abrabr_268_20,0.0
lowfield magnetic stimulation improved cuprizoneinduced depressionlike symptoms demyelination female mice exp ther med 2022 mar 23 3 210 doi 103892 etm202211133 epub 2022 jan 7abstractdepression common disabling comorbidity multiple sclerosis ms currently clear guidelines treatment lowfield magnetic stimulation lfms novel noninvasive neuromodulation intervention previously demonstrated rapidly alleviate mood disorders aim present study investigate effects lfms depressionlike behaviors demyelination wellestablished mouse model ms c57bl 6 female mice fed 02 cuprizone cpz diet 3 6 weeks induce acute demyelination time mice treated either sham lfms 20 min day 5 days week 3 6 weeks treatment behavior assessed open field task ymaze forced swim test prefrontal cortex hippocampus collected perform immunohistochemistry western blot analysis verify myelination status cpz diet cause significant locomotor deficits however working memory measured using y maze depressionlike behavior adaptive learning assayed using forced swim test significantly impaired animals lfms treatment demonstrated significant antidepressantlike effect markedly attenuated cpzinduced demyelination prefrontal cortex 3 6weeks treatment observed changes myelin basic protein immunostaining western blot analysis therefore results present study indicated lfms may promising therapy demyelinating diseases due improvement depressive symptoms via regulation myelination cortical areaspmid35126713 pmcpmc8796645 doi103892 etm202211133,1.0
inhibition sc4mol hsd17b7 shifts cellular sterol composition promotes oligodendrocyte formation rsc chem biol 2021 oct 21 3 1 5668 doi 101039 d1cb00145k ecollection 2022 jan 5abstractwhile cholesterol biosynthesis pathway extensively studied recent work forged new links inhibition specific sterol pathway enzymes accumulation unique sterol substrates biological areas diverse cancer immunology neurodegenerative disease recently reported dozens small molecules enhance formation oligodendrocytes glial cell type lost multiple sclerosis inhibiting cyp51 sterol 14reductase ebp inducing cellular accumulation 8 9unsaturated sterol substrates several adjacent pathway enzymes also 8 9unsaturated sterol substrates yet evaluated potential targets oligodendrocyte formation many biological contexts part due lack available smallmolecule probes show genetic suppression sc4mol hsd17b7 increases formation oligodendrocytes additionally identified optimized multiple potent new series sc4mol hsd17b7 inhibitors shown small molecules enhance oligodendrocyte formation sc4mol inhibitor cw4142 induced accumulation sc4mols sterol substrates mouse brain represents vivo probe sc4mol activity mechanistically cellular accumulation 8 9unsaturated sterols represents central driver enhanced oligodendrocyte formation exogenous addition purified sc4mol hsd17b7 substrates 8 9saturated analogs promotes opc differentiation work validates sc4mol hsd17b7 novel targets promoting oligodendrocyte formation underlines broad role 8 9unsaturated sterols enhancers oligodendrocyte formation establishes first highquality small molecules targeting sc4mol hsd17b7 novel tools probing diverse areas biologypmid35128409 pmcpmc8729178 doi101039 d1cb00145k,0.0
covid19 physical activity behaviour people neurological diseases systematic review j dev phys disabil 2022 feb 1126 doi 101007 s1088202209836x online ahead printabstractthe covid19 pandemic led radical lifestyle change may unintendedly change physical activity levels aimed perform systematic review investigate physical activity changes people neurological diseases examine relationship physical activity disease symptoms psychosocial factors review performed accordance preferred reporting items systematic reviews metaanalyses prisma statement systematic search literature across five databases pubmed cinahl web science scopus cochrane library carried using keywords relating covid19 physical activity sedentary behaviour exercise name neurological diseases systematic search updated 4 february 2021 keywords fourteen studies n 7662 persons neurological diseases n 1663 healthy controls eligible review study populations parkinson disease n 7 dementia n 1 multiple sclerosis n 1 spinal cord injury n 1 hereditary spastic paraplegia n 1 neuromuscular diseases n 1 charcotmarietooth neuropathy n 1 epilepsy n 1 thirteen studies reported decreased physical activity level one study reported high interruption rate physiotherapy rehabilitation furthermore physical activity reduction associated worse disease symptoms depression perceived health mental physical components quality life covid19 pandemic negative impact physical activity levels people neurological diseases change related worsening disease symptoms psychosocial factors registration number protocol review registered prospero database crd42020207676 supplementary information online version contains supplementary material available 101007 s1088202209836xpmid35125854 pmcpmc8803459 doi101007 s1088202209836x,0.0
type exercise beneficial quality life people multiple sclerosis network metaanalysisselect background overwhelming evidence regarding beneficial effects exercise management symptoms functionality healthrelated quality life hrqol people multiple sclerosis ms however analyses compared different types exercise objective aim network metaanalysis nma assess type physical exercise greatest positive effect hrqol people ms methods medline cochrane library embase web science physiotherapy evidence database sportdiscus databases searched inception june 2021 identify randomized controlled trials rcts examining effect physical exercise hrqol people ms nma included pairwise indirect comparisons ranked effect interventions calculating surface cumulative ranking sucra results included 45 rcts nma 2 428 participants 76 women mean age 45 years five types physical exercises ranked sensorimotor training highest effect size 087 95 confidence interval ci 060 115 highest sucra 87 total hrqol highest effect size sucra physical mental hrqol aerobic exercise 085 95 ci 028 142 89 mindbody exercises 054 95 ci 003 106 89 sensorimotor training best exercise mild disease aerobic exercise severe disease total hrqol conclusions sensorimotor training seems effective exercise improve hrqol aerobic mindbody exercises improve physical mental hrqol respectively,0.0
elimination circulating epsteinbarr virus infected b cells underlies anticd20 monoclonal antibody activity multiple sclerosis hypothesis abstractmultiple sclerosis chronic immunemediated disease central nervous system aspects repetitive inflammatory activity well slow neurodegenerative process immune assault nervous system triggered complex interaction immunogenetic environmental factors among different environmental factors compelling case buttressed strong epidemiological serological data made role epsteinbarr virus ebv pathogenesis ms however ubiquity ebv lack well understood role ms pathogenesis controversies regarding presence brains people ms caused debate exactly contributes ms recent years seen remarkable effect anticd20 therapies inflammatory component ms b cell depletion results salutary effect ms remains incompletely understood proposed depletion cd20+ bcells disrupts proinflammatory pathways immune system especially tcells paper make case robust effect anticd20 therapies ms activity actually removal circulating ebvinfected memory bcells drive cns inflammation immune pathways essence antiviral effect necessarily immunomodulatory effect,0.0
effect combined action observation therapy eccentric exercises treatment midportion achilles tendinopathy study protocol feasibility pilot randomised controlled trial background midportion achilles tendinopathy common overuse injury can difficult successfully rehabilitate whilst peripherally directed treatment approaches strengthen achilles tendon complex can efficacious individuals others will continue experience longstanding pain functional deficits expanding rehabilitation approach beyond tendon mechanical properties include techniques target central neurophysiological changes can occur chronic injuries including midportion may improve rehabilitation outcomes action observation therapy aot one technique targets central changes can enhance motor learning knowledge currently available information combined effect aot eccentric exercises rehabilitation midportion understanding feasibility conducting randomised controlled trials investigate combined centrally peripherally directed treatment approach protocol outlines design remotely conducted parallelgroup randomised controlled trial comparing efficacy combined aot eccentric loading exercises versus eccentric loading exercises alone midportion atmethodsparticipants recruited throughout ireland midportion will randomly assigned one following groups aot group will observe videos eccentric exercises prior physical performance eccentric exercises ii control group will observe videos landscapes prior performance eccentric exercises 12week daily intervention per alfredson loading protocol outcome measures will assessed baseline week 6 week 12 primary feasibility outcomes will include data numbers eligible participants recruitment retention rates along exercise compliance acceptability treatment primary clinical outcome measure will victorian institution symptom assessmentachilles questionnaire visaa assessing disability secondary clinical outcomes will address remaining core domains outlined international scientific tendinopathy symposium consensus icon group including pain participation functional physical function capacity quality life psychological factors widespread bodily pain centralised pain features patient satisfaction levels will also evaluateddiscussionthis study will provide scientific direction future randomised controlled trials exploring effect aot eccentric exercises treatment midportion pain centralised pain features motor nonmotor functions quality life patient satisfaction levels feasibility conducting study remotely participant screening final followup assessment will also providedtrial registration isrctn58161116,0.0
gas6 induces inflammation reduces plaque burden worsens behavior sexdependent manner app#x2f ps1 model alzheimers disease background alzheimers disease leading cause dementia worldwide tam receptor tyrosine kinases tyro3 axl mertk known role engagement phagocytosis modulation inflammation recent evidence suggests complex relationship axl mer microglial phagocytosis amyloid plaques ad gas6 primary cns tam ligand reduces neuroinflammation improves outcomes murine models cns disease therefore hypothesized aavmediated overexpression gas6 alleviate plaque pathology reduce neuroinflammation improve behavior app ps1 model alzheimers diseasemethodsadenoassociated viral vectors used overexpress gas6 app ps1 model alzheimers disease ninemonthold male female app ps1 nontransgenic littermates received bilateral stereotactic hippocampal injections aavgas6 aavcontrol expresses nonfunctional gas6 protein one month injections mice underwent battery behavioral tasks assess cognitive function brains processed immunohistochemical transcriptional analysesresultsgas6 overexpression reduced plaque burden male app ps1 mice however contrary hypothesis gas6 increased proinflammatory microglial gene expression worsened contextual fear conditioning compared controltreated mice gas6 overexpression appeared effect phagocytic mechanisms vitro vivo measured cd68 immunohistochemistry microglial methoxy04 uptake primary microglial uptake fluorescent fibrillar amyloid betaconclusionour data describes triad worsened behavior reduced plaque number increase proinflammatory signaling sexspecific manner gas6 historically induced antiinflammatory signatures peripheral nervous system data suggest alternative proinflammatory role context alzheimers disease pathology,1.0
artificial intelligence diagnosis multiple sclerosis systematic review abstractbackground recent years artificial intelligence ai techniques rapidly evolving clinical practices diagnosis prognosis processes assess treatment effectiveness monitoring diseases previous studies showed interesting results regarding diagnostic efficiency ai methods differentiating multiple sclerosis ms patients healthy controls demyelinating diseases great lack comprehensive systematic review study role ai diagnosis ms aimed perform systematic review document performance ai ms diagnosismethods systematic search performed using four databases including pubmed scopus web science ieee august 2021 original studies focused deep learning ai analyze modalities purpose diagnosing ms included studyresults finally 38 studies included systematic review abstract fulltext screening total 5433 individuals included including 2924 cases ms 2509 healthy controls sensitivity specificity reported 29 studies ranged 7692 100 sensitivity 74 100 specificity furthermore 34 studies reported accuracy ranged 81 100 among included studies magnetic resonance imaging mri 20 studies oct six studies serum cerebrospinal fluid markers six studies movement function three studies modalities breathing evoked potential used detecting ms via aiconclusion conclusion diagnosis ms based new markers ai growing field research mri images followed images obtained oct serum csf biomarkers motor associated markers results show advances made ai way monitor diagnose ms patients can change drastically,1.0
mildtosevere traumatic brain injury children altered cytokines reflect severity background paediatric traumatic brain injury tbi recognised significant longerterm neurocognitive effects childhood time high risk head injury functional recovery variable combination physical cognitive emotional impairment immune activation alteration cytokine levels present following tbi may differ adultsmethodspro antiinflammatory cytokines including interleukin il 2 il4 il6 il8 il10 il17a tumor necrosis factor tnf interferon ifn examined baseline following vitro treatment endotoxin whole blood following children severe tbi stbi initial glasgow coma scale gcs 8 mild tbi mtbi gcs 14 15 04d 1014d posttbi compared healthy agematched controlsresultsthe study enrolled 208 children including 110 tbi cohort n 104 mild 6 severe controls n 98 baseline children tbi increased il6 mtbi group significantly increased ifn versus controls stbi baseline ifn decreased compared controls baseline il8 il10 il17a tnf decreased mtbi compared controls persisted 2 week postmtbi auc detecting mtbi 0801 ci 073086 using il6 il10 ratio mtbi showed greater fold change il8 tnf response endotoxin stimulation response persisted 2 weeks children stbi significant il6 response endotoxin show increase il17aconclusionchildren tbi including mtbi show altered cytokine profiles altered endotoxin responses although cytokines increased stbi especially response endotoxin suppressed responses found mtbi coupled persistent immune dysfunction postinjury,0.0
abnormal respiratory progenitors fibrotic lung injury abstractrecent advances singlecell rna sequencing scrnaseq epithelium lineage labeling yielded identification multiple abnormal epithelial progenitor populations alveolar type 2 atii cell differentiation alveolar type 1 ati cells regenerative lung postfibrotic injury abnormal cells include basaloid basallike cells atii transition cells persistent epithelial progenitors peps cells occurred accumulated regeneration distal airway alveoli response chronic acute pulmonary injury among alveolar epithelial progenitors peps express distinct krt8+ phenotype rarely found intact alveoli however postinjury krt8+ phenotype seen dysplastic epithelial cells fully understanding characteristics functions newly found injuryinduced abnormal behavioral epithelial progenitors signaling pathways regulating phenotype potentially point way unique therapeutic targets fibrosing lung diseases review summarizes recent advances understanding epithelial progenitors relate uncovering regenerative mechanisms,0.0
identifying factors affecting patient engagement exercise rehabilitation background despite proven benefits exercise rehabilitation numerous health conditions musculoskeletal injuries recovery surgery patient adherence programs reported often less 35 increasing patient engagement therefore potential improve patient health outcomes benefiting patient carers services support aims review identify factors contribute patient engagement prescribed exercise rehabilitation using comb capability opportunity motivationbehaviour framework behavioural analysismethodsfive electronic databases pubmed embase cochrane web science clinicaltrialsgov searched comb key word searched specifically within titles abstracts combined either physical activity exercise included using operation records filtered excluded following fulltext screening based predetermined eligibility criteriaresultstwenty studies included review main comb themes highlighted improving patient engagement capabilityimproving patient knowledge cognitive skills behavioural regulation action planning action control also benefit timemanagement opportunitya balanced life situation enabled time devoted exercise program social support easily accessible affordable resources services motivationincreasing patient levels selfefficacy autonomous motivation noted influenced levels perceived capability additionally motivation noted influenced patients perceiving benefits exercise adherence program promoted goalsetting issues capability domain included fear dislike exerciseconclusionpatient engagement behavior shown influenced external opportunity intrapersonal variables capability motivation prescribing exercises within rehabilitation program need discuss factors patients codesign exercise rehabilitation program partnership patient since likely improve patient engagement thereby result superior health outcomes furthermore factors need consideration clinical trials findings trials translate mainstream healthcare settings,0.0
transitions longterm home ventilator engagement study transitions live study protocol pragmatic randomized controlled trial background overview rationalewe codeveloped multicomponent virtual care solution ttlive home mechanical ventilation hmv population using atouchaway platform aetonix ttlive intervention includes 1 virtual home visits 2 customizable care plans 3 clinical workflows incorporate reminders completion symptom profiles telemonitoring 4 digitally secure communication via messaging audio video calls 5 resource library including print audiovisual materialobjectives brief methodsour primary objective evaluate ttlive intervention compared usual care control group using eightcenter pragmatic parallelgroup singleblind outcome assessors randomized controlled trial eligible patients children adults newly transitioning hmv ontario canada target sample size 440 participants 220 arm coprimary outcomes number emergency department ed visits 12 months randomization change family caregiver fc reported pearlin mastery scale score baseline 12 months secondary outcomes also measured 12 months post randomization include healthcare utilization measured using hybrid ambulatory home care record ahcrhybrid fc burden using zarit burden interview healthrelated quality life using eq5d addition will conduct costutility analysis 1year time horizon measure process outcomes including healthcare provider time using care coordination measurement tool will use qualitative interviews subset study participants understand acceptability barriers facilitators ttlive intervention will administer family experiences care coordination fecc interview participants will use poisson regression number ed visits 12 months will use linear regression pearlin mastery scale score 12 months will adjust baseline score estimate effect intervention primary outcomes analysis secondary outcomes will employ regression causal linear mixed modeling primary analysis will follow intentiontotreat principles research ethics board approval sickkids childrens hospital eastern ontario mcmaster childrens hospital childrens hospitallondon health sciences sunnybrook hospital london health sciences west park healthcare centre ottawa hospitaldiscussionthis pragmatic randomized controlled singleblind trial will determine effectiveness costeffectiveness ttlive virtual care solution compared usual care providing important data patient family experience well process measures healthcare provider time deliver interventiontrial registrationclinicaltrialsgov nct04180722 registered november 27 2019,0.0
accurate identification circrna landscape complexity reveals pivotal roles human oligodendroglia differentiation background circular rnas circrnas novel class poorly conserved noncoding rnas regulate gene expression highly enriched human brain despite increasing discoveries circrna function human neurons circrna landscape function developing human oligodendroglia myelinating cells govern neuronal conductance remains unexplored meanwhile improved experimental computational tools accurate identification circrnas neededresultswe adopt published experimental approach circrna enrichment develop carp circrna identification using atailing rnase r approach pseudoreference alignment comprehensive 21module computational framework accurate circrna identification quantification using carp identify developmentally programmed human oligodendroglia circrna landscapes hog oligodendroglioma cell line distinct neuronal circrna landscapes numerous circrnas display oligodendrogliaspecific regulation upon differentiation among subclass regulated independently parental mrnas find circrna flanking introns often contain cisregulatory elements rna editing predicted bind differentiationregulated splicing factors addition discover novel oligodendrogliaspecific circrnas predicted sponge micrornas cooperatively promote oligodendroglia development furthermore identify circrna clusters derived differentiationregulated alternative circularization events within gene containing common circular exon achieving additive sponging effects promote human oligodendroglia differentiationconclusionsour results reveal dynamic regulation human oligodendroglia circrna landscapes early differentiation suggest critical roles circrnamirnamrna axis advancing human oligodendroglia development,1.0
emerging roles inflammationmediated endothelialmesenchymal transition health disease abstractendothelialmesenchymal transition endomt cellular differentiation process endothelial cells ecs lose properties differentiate mesenchymal cells observed development also various pathological states adults including cancer progression organ tissue fibrosis transforming growth factor tgf inflammationrelated cytokine shown play central roles induction endomt tgf induces endomt regulating expression various transcription factors signaling molecules cellular components confer ecs mesenchymal characteristics however tgf necessarily sufficient induce endomt promote progression endomtrelated diseases refractory extent addition tgf additional activation inflammatory factors often required stabilize progression endomt since recent lines evidence indicate inflammatory signaling molecules act enhancers endomt summarize roles inflammatory factors induction endomt related diseases hope review will help develop therapeutic strategies endomtrelated diseases targeting inflammationmediated endomt,0.0
edaravone ameliorates depressive anxietylike behaviors via sirt1#x2f nrf2#x2f ho1#x2f gpx4 pathway background inflammation oxidative stress os considered crucial components pathogenesis depression edaravone eda free radical scavenger processes strong biological activities including antioxidant antiinflammatory neuroprotective properties however role potential molecular mechanisms depression remain unclear present study aimed investigate antidepressant activity eda underlying mechanismsmethodsa chronic social defeat stress csds depression model performed explore whether eda produce antidepressant effects behaviors tests carried examine depressive anxietylike cognitive behaviors including social interaction si test sucrose preference test spt open field test oft elevated plus maze epm novel object recognition tail suspension test tst forced swim test fst hippocampal medial prefrontal cortex mpfc tissues collected nissl staining immunofluorescence targeted energy metabolomics analysis enzymelinked immunosorbent assay elisa measurement mda sod gsh gshpx taoc transmission electron microscopy tem western blotting wb quantitative realtime polymerase chain reaction qrtpcr detected sirt1 nrf2 ho1 gpx4 signaling pathway ex527 sirt1 inhibitor ml385 nrf2 inhibitor injected intraperitoneally 30 min eda injection daily knockdown experiments performed determine effects gpx4 csds mice eda treatment adenoassociated virus aav vector containing mirnai gpx4 egfp infusionresultsthe administrated eda dramatically ameliorated csdsinduced depressive anxietylike behaviors addition eda notably attenuated neuronal loss microglial activation astrocyte dysfunction oxidative stress damage energy metabolism proinflammatory cytokines activation hippocampus hip mpfc csdsinduced mice examination indicated application eda csds model significantly increased protein expressions sirt1 nrf2 ho1 gpx4 hip ex527 abolished antidepressant effect eda well protein levels nrf2 ho1 gpx4 similarly ml385 reversed antidepressant anxiolytic effects eda via decreased expressions ho1 gpx4 addition gpx4 knockdown csds mice abolished edagenerated efficacy depressive anxietylike behaviorsconclusionthese findings suggest eda possesses potent antidepressant anxiolytic properties sirt1 nrf2 ho1 gpx4 axis gpx4mediated ferroptosis may play key role effect,1.0
lowering blood cholesterol affect neuroinflammation experimental autoimmune encephalomyelitis background multiple sclerosis ms chronic disabling disease central nervous system cns commonly affecting young adults increasing evidence environmental factors important development course ms metabolic syndrome mets comprises dyslipidemia associated worse outcome ms disease furthermore lipidlowering drug class statins proposed improve ms disease course however cholesterol also ratelimiting myelin biogenesis promotes remyelination ms animal models thus impact circulating blood cholesterol levels disease remains debated controversialmethodswe assessed role circulating cholesterol murine model ms experimental autoimmune encephalomyelitis eae disease using two different approaches 1 mouse model familial hypercholesterolemia induced lowdensity lipoprotein receptor ldlr deficiency 2 use monoclonal antipcsk9 neutralizing antibody alirocumab reduces ldlr degradation consequently lowers blood levels cholesterolresultselevated blood cholesterol levels induced ldlr deficiency worsen clinical symptoms mice eae addition observed antipcsk9 antibody alirocumab influence eae disease course modulate immune response eaeconclusionsthese findings suggest blood cholesterol level direct role neuroinflammatory diseases previously shown protective effects statins ms related circulating cholesterol,1.0
crewed journey mars implications human microbiome abstracta human spaceflight mars scheduled next decade preparation unmatched endeavor plethora challenges must faced prior actual journey mars mission success will depend health crew working capacity hence journey mars will also depend microbiome farreaching effects individual crew health spaceships integrity food supply human beings rely microbiome microbes essential managed ensure beneficial effects outweigh potential risks commentary focus current state knowledge regarding healthy gut microbiome space travelers based research international space station simulation experiments earth indicate essential knowledge gaps microbial conditions longterm space missions isolated confined space habitats outposts give detailed recommendations microbial monitoring preflight inflight postflight finally conclusion outlines open questions aspects space travelers health beyond scope commentary video abstract,0.0
comprehensive review varicellazoster virus herpes simplex virus cryptococcal infections associated sphingosine1phosphate receptor modulators multiple sclerosis patients abstractsphingosine1phosphate s1p receptor modulators new class oral diseasemodifying therapies used multiple sclerosis ms immunomodulatory drugs can thus increase risk certain infections patients paper summarizes existing data common opportunistic infections associated drugs class varicella zoster virus vzv herpes simplex virus hsv cryptococcus neoformans literature review descriptive analysis reported cases clinical phase iii study findings incidences infections conducted using pubmed google scholar results regarding fingolimod siponimod ozanimod ponesimod obtained overall incidence infections found extremely low ms patients treated s1p receptor modulators among four drugs class incidence rates vzv hsv cryptococcal infections either similar slightly higher placebo infections reported cases ozanimod ponesimod resulted favorable outcomes disabilities fatalities however paper highlights increasing relevance assessing infectious risk factors promote early identification serious complications related drugs opportunistic infections considered differential diagnosis ms relapse setting diseasemodifying treatment,0.0
impaired sequential preserved motor memory consolidation multiple sclerosis disease neuroscience 2022 feb 3s03064522 21 006539 doi 101016 jneuroscience202112029 online ahead printabstractstudies investigating motor learning patients multiple sclerosis ms disease highlighted ms patients exhibit similar learning performance healthy controls learning can hampered progression ms eventually leading impaired efficiency subcorticalcortical networks aimed investigating whether longterm overnight consolidation sequential motor memories preserved ms disease 31 patients ms two healthy control groups 27 young 14 middle age tested two consecutive days using serial reaction time task performance tested 20 minutes end learning day 1 monitor transient offline shortterm increase motor sequential performance b 24h day 2 quantify overnight delayed changes performance reflecting memory consolidation besides slower overall rt patients ms motor performance similarly evolved groups sequence learning assessed interference effects similar patients ms control groups day 1 learning 20min test contrast interference effects keep increasing day 2 24h relearning healthy control groups reverted levels reached end learning patients ms longterm consolidation sequential knowledge impaired patients ms motor level learning overnight consolidation abilities preserved ms diseasepmid35124165 doi101016 jneuroscience202112029,0.0
serum hgf apn2 associated disability worsening spms j neuroimmunol 2021 dec 30 364577803 doi 101016 jjneuroim2021577803 online ahead printabstractthere reliable biomarkers predict disability worsening progressive multiple sclerosis ms analyzed circulating biomarkers hypoxia angiogenesis people secondary progressive ms spms participated clinical trial monitored prospectively disability worsening concentrations glucose transporter1 glut1 marker hypoxia higher spms compared controls moreover low levels angiopoietin2 apn2 hepatocyte growth factor hgf associated disability worsening neurofilament light emerging biomarker ms apn2 hgf neurotrophic potential biomarkers therapeutic targets spmspmid35124365 doi101016 jjneuroim2021577803,0.0
mcc950 treatment nlrp3mediated inflammatory diseases latest evidence therapeutic outcomes int immunopharmacol 2022 feb 3 106108595 doi 101016 jintimp2022108595 online ahead printabstractevidence suggests various innate immune system components involved pathological inflammatory conditions among components nlr family pyrin domain containing 3 nlrp3 inflammasome can participate destructive inflammatory responses inducing production active form inflammatory cytokines nlrp3 involved pathogenesis several inflammatory autoimmune diseases type 2 diabetes mellitus multiple sclerosis ms atherosclerosis alzheimers disease ad cryopyrinassociated periodic syndrome caps infectious diseases therefore inhibition nlrp3 can useful treatment option inflammatory diseases regard mcc950 small molecule capable inhibiting nlrp3 following inhibition nlrp3 production interleukin1 il1 il18 proinflammatory cytokines reduced interestingly mcc950 can inhibit nlrp3 inflammasomes nlrp1 nlr family card domain containing 4 nlrc4 review summarized structure mechanism action mcc950 control nlrp3dependent inflammation role mcc950 treatment nlrp3mediated inflammatory diseases based latest studiespmid35124417 doi101016 jintimp2022108595,0.0
vailability fibrinogen#x2f albumin ratio ms attack abstractbackground aim multiple sclerosis ms chronic central nervous system inflammatory disease fibrinogen albumin ratio far studied inflammatory marker past significant relationship inflammation shown study examined serum levels albumin fibrinogen far patients presenting ms attack investigated usability diagnosis management ms attacksmaterials methods retrospective study included 40 patients admitted hospital ms attack 40 control patients patientsnull demographics medical history mean expanded disability status scale edss imaging findings laboratory tests extracted medical records patientsnull fibrinogen albumin levels recorded blood tests performed steroid administration far values calculated patientsnull controlsnull results comparedresults fibrinogen far values significantly higher patient group p0001 difference patient control groups terms albumin p0 16 significant relationship found parameters edss disease duration smoking status far value p005 conclusion serum fibrinogen far levels patients presenting attack significantly higher control group far value vary disease duration edss score based information far may useful indicator ms attack regardless edss disease duration,0.0
systematic review metaanalysis mycobacterium avium subsp paratuberculosis environmental trigger multiple sclerosis mapassociated multiple sclerosis abstractmycobacterium avium subsp paratuberculosis map identified one environmental agents causes multiple sclerosis ms global prevalence ms upsurging years however efforts divulge role map ms limited result present study aimed assessing odd ratios ors associated map risk ms maprelated ms data obtained 6 databases using terms nullmultiple sclerosisnull nullmsnull nullparatuberculosisnull without regard time language restrictions following prisma standards total 2 538 participantsnull data 12 studies presenting antimap antibodies map dna 4 studies fitted randomeffects re fixedeffects fe metaanalytic models furthermore betweenstudy heterogeneity measured using i2values significant limit set 75 analytical rigour publication bias determined using leaveoneoutanalytics eggernulls tests pcurve analysis fe re models antimap antibodies data significantly associated ms risk map 1071 95ci 778 1474 pvalue 00001 1276 95ci 813 2002 pvalue 00001 respectively i2 value 349 95ci 00 672 pvalue011 similarly map dna dataset fe significantly present ms risk due map 553 95ci 354 866 pvalue 00001 re showed 527 95ci 322 860 p00017 i2value00 95ci 00 847 pvalue071 eggersnull test hand found publication bias antimap antibodies data intercept161 95 ci 045 277 t272 p0021 map dna dataset intercept557 95 ci 2044 929 t074 p054 robustness metaanalyses demonstrated sensitivity analyses addition evidence phacking observed rightskewness test pfull 0001 phalf 0001 statistical power 94 95ci 72599 conclusion synthesis revealed strong association map ms indicating map significant environmental agent may trigger ms thus early screening map ms cases may assist therapeutic approach management treatment therefore future studies tailored towards role map severity ms phenotypes well address global data gaps low disease surveillance,0.0
treatment multiple sclerosis children brief overview clin immunol 2022 feb 2108947 doi 101016 jclim2022108947 online ahead printabstractmultiple sclerosis ms common autoimmune chronic inflammatory demyelinating disorder central nervous system pediatriconset ms poms opposed adultonset ms aoms rare condition presenting similar clinical features aoms active course disease higher relapse rates greater white grey matter damage date therapeutic approaches treat poms extrapolated observational studies data trials conducted adults raising concerns efficacy safety pediatric population herein discuss common therapeutic strategies used poms management basing individual clinical practice experiencepmid35123059 doi101016 jclim2022108947,1.0
elevated levels il32 cerebrospinal fluid neurobehcet disease correlation nlrp3 inflammasome j neuroimmunol 2022 jan 30 365577820 doi 101016 jjneuroim2022577820 online ahead printabstractinterleukin32 il32 proinflammatory cytokine induces cytokines involved inflammation including tumour necrosis factor tnf il6 il1 objective study evaluate il32 nlrp3 inflammasome il1 il6 il17a tnfa il10 il37 cerebrospinal fluid csf paired serum samples patients neurobehcet disease nbd elisa rtpcr western blotting analysis receiver operating characteristic roc curve employed explore predictive value il32 levels il32 il1 il6 il17 tnf highly expressed csf nbd multiple sclerosis ms patients contrasting low levels patients noninflammatory neurological diseases nind headache attributed bd habd il32 nlrp3 inflammasome nbd correlate significantly crp esr il32 studied potential bd biomarker inflammation nbdpmid35123164 doi101016 jjneuroim2022577820,0.0
ionic mitigation cd4+ t cell metabolic fitness th1 central nervous system autoimmunity th2 asthmatic airway inflammation therapeutic zinc sci rep 2022 feb 4 12 1 1943 doi 101038 s41598022048276abstractt helper th cells provide immunity pathogens also contribute detrimental immune responses allergy autoimmunity th2 cells mediate asthmatic airway inflammation th1 cells involved pathogenesis multiple sclerosis t cell activation involves complex transcriptional networks metabolic reprogramming enable proliferation differentiation th1 th2 cells essential trace element zinc reported immunomodulatory capacity high zinc concentrations interfere t cell function however high doses zinc affect t cell gene networks metabolism remained far elusive herein demonstrate means transcriptomic analysis zinc aspartate unizink registered pharmaceutical infusion solution high bioavailability negatively regulates gene networks controlling dna replication energy metabolism murine cd3 cd28activated cd4+ t cells specifically presence zinc cd4+ t cells show impaired expression cell cycle glycolytic tricarboxylic acid cycle genes functionally cumulates reduced glycolysis oxidative phosphorylation metabolic fitness viability moreover high zinc concentrations impaired nuclear expression metabolic transcription factor myc prevented th1 th2 differentiation vitro reduced th1 autoimmune central nervous system cns inflammation th2 asthmatic airway inflammation induced house dust mites vivo together find higher zinc doses impair metabolic fitness cd4+ t cells prevent th1 cns autoimmunity th2 allergypmid35121767 doi101038 s41598022048276,0.0
neuroprotective effects transdifferentiation astrocytes dopaminergic neurons ginkgolide k parkinson#39 disease mice j neuroimmunol 2022 jan 7 364577806 doi 101016 jjneuroim2022577806 online ahead printabstractparkinsons disease pd chronic progressive movement disorder caused selective loss midbrain dopaminergic neurons unknown etiology now although great development treatments pd cures neuroprotective nerve regenerative effects underway pd patients reported neuroprotective effects ginkgolide k gk mice upon acute mptp exposure gk ameliorated gait dysfunction dopaminergic neuron loss gk exhibits ability immunomodulation including switching microglia m2 phenotype decreasing microgliamediated inflammation inhibiting peripheral cd4+ifn+ cd4+il17+ t cells synuclein specific autoantibodies expression neurotrophic factors bdnf gdnf nt3 promoted treatment gk mptp mice brains notably gk enhanced expression nestin gfap+ astrocytes followed transdifferentiation astrocytetoneuron independent wnt signaling although gk induced expression wnt signaling astrocytes based results work implicates therapeutic potential gk protecting th+ neurons multiple intercellular pathways modify nerve regeneration mptp mice however exactly cellular molecular mechanisms need explored confirmedpmid35121334 doi101016 jjneuroim2022577806,1.0
lesion volume relapsing multiple sclerosis associated perivascular space enlargement level basal ganglia ajnr j neuroradiol 2022 feb 43 2 238244 doi 103174 ajnra7398abstractbackground purpose perivascular spaces surround blood vessels brain involved neuroimmune functions clearance metabolites via glymphatic system brain enlarged perivascular spaces marker dysfunction processes therefore highly relevant monitoring disease activity ms study aimed compare number enlarged perivascular spaces people relapsing ms mr imaging markers inflammation brain atrophymaterials methods fiftynine patients 18 clinically isolated syndrome 22 early 19 late relapsingremitting ms scanned longitudinally mean followup duration 196 sd 05 months using t2weighted t1weighted flair mr imaging two expert raters identified counted enlarged perivascular spaces t2weighted mr images 3 rois centrum semiovale basal ganglia midbrain baseline change time number enlarged perivascular spaces correlated demographics lesion brain volumesresults late relapsingremitting ms greater average number enlarged perivascular spaces baseline level basal ganglia 723 compared early relapsingremitting ms 605 clinically isolated syndrome 547 f 34 p 042 finding correlated lesion volume r 044 p 0004 brain atrophy r 016 enlarged perivascular spaces increased number time regions rate increase differ among clinical groupsconclusions enlarged perivascular spaces level basal ganglia associated greater neuroinflammatory burden rate enlargement appears constant patients relapsingremitting disease phenotypespmid35121585 doi103174 ajnra7398,0.0
scalp dysesthesia neuropathic phenomenon j eur acad dermatol venereol 2022 feb 5 doi 101111 jdv17985 online ahead printabstractscalp dysesthesia abnormal sensation scalp absence cutaneous disease characterized burning itching sensation can related variety neurogenic psychogenic causes condition extremely bothersome also common especially amongst geriatric population women patients diabetes mellitus patients psychiatric history however despite prevalence many populations limited data causes characteristics given limited cutaneous manifestations also easily misdiagnosed underrecognized cause scalp pruritus dermatological community therefore education scalp dysesthesia paramount helping physicians identify provide appropriate treatment patients review focuses predominately neurogenic causes brief review psychogenic itch scalp dysesthesia therapeutics found effective condition neurogenic causes scalp dysesthesia occur damage central peripheral pathways itch sensation resulting modification heightened sensitivity nerves result abnormal sensations absence proportion external stimuli comprehensive review etiologies provided ranging lesions central nervous system caused cervical spine disease trigeminal trophic syndrome tumor stroke multiple sclerosis small fiber neuropathies caused diabetes brow lifts keloid burn scarring recently also reports scalp dysesthesias associated postinfectious covid19 treatment options tailored towards disease severity different causes disease will also discussed elucidating different mechanisms therapeutic treatments scalp dysesthesia hope provide clinicians tools identify treat condition well encourage research etiologies therapeuticspmid35122352 doi101111 jdv17985,0.0
tracking neural stem cells vivo achievements limitations stem cell rev rep 2022 feb 5 doi 101007 s1201502210333z online ahead printabstractneural stem cell nsc therapies developing rapidly proposed treatment option various neurological diseases stroke parkinsons disease multiple sclerosis however monitoring transplanted nscs exploring location migration evaluating efficacy safety become serious important issues two main problems tracking nscs noted labeling visibility imaging direct labeling reporter gene labeling two main methods labeling stem cells magnetic resonance imaging nuclear imaging including positron emission tomography singlephoton emission computed tomography optical imaging commonly used imaging techniques strengths weaknesses thus multimodal imaging combines two imaging methods complement advantages disadvantages garnered increased attention advances image fusion nanotechnology well exploration new tracers new imaging modalities substantially facilitated development nsc tracking technology however safety issues related tracking longterm tracking cell viability still challenges review discuss merits defects different labeling imaging methods well recent advances challenges prospects nsc trackingpmid35122628 doi101007 s1201502210333z,0.0
successful longterm management spasticity people multiple sclerosis using software application results randomizedcontrolled multicenter study eur j neurol 2022 feb 4 doi 101111 ene15271 online ahead printabstractbackground successful longterm treatment spasticity people multiple sclerosis pwms challenging investigated effects multidisciplinary inpatient rehabilitation mir individualized selftraining program delivered app spasticity pwmsmethods first assessed efficacy 4weeks mir ambulatory pwms edss70 moderate severe lower limb spasticity defined 4 points numeric rating scale spasticity nrss cohort 115 pwms 7 rehabilitation centers austria case clinically relevant improvement spasticity 20 nrss following mir n94 pwms randomly allocated 11 ratio either newly designed msspasticity app paperbased selftraining program 12 weeks primary outcome change nrss drks00023960 results mir led significant reduction 20 points nrss 95 confidence interval ci 25 20 p0000 mir associated statistically significant improvement spasticity modified ashworth scale strength mobility outcomes following mir selftraining msspasticity app associated sustained positive effect nrss paperbased selftraining led worsening spasticity median nrss difference 10 95 ci 17 03 p0009 msspasticity app also associated significantly better adherence selftraining 95 versus 72 completion rate p0001 conclusion pwms mir able significantly improve lowerlimb spasticity strength mobility following mir individually tailored antispasticity program delivered app leads sustained positive longterm managementpmid35122365 doi101111 ene15271,1.0
cathepsin b inhibitor alleviates th1 th17 th22 transcription factor signaling dysregulation experimental autoimmune encephalomyelitis exp neurol 2022 feb 2113997 doi 101016 jexpneurol2022113997 online ahead printabstractmultiple sclerosis ms autoimmune disease characterized inflammatory infiltration association demyelination central nervous system among factors involved immunological mechanisms ms th1 th17 th22 cells play critical role present study investigated role ca074 potent cathepsin b inhibitor ms progression using sjl j mouse model experimental autoimmune encephalomyelitis eae following induction eae mice administered ca074 10 mg kg intraperitoneally day beginning day 14 continuing day 28 evaluated clinical signs investigated effect ca074 th1 tbet stat4 th17 il17a rort th22 tnf il22 regulatory t treg foxp3 cells spleen using flow cytometry also analyzed effect ca074 tbet il17a rort il22 mrna protein levels using rtpcr western blot analysis brain tissues cathepsin b expression also assessed western blot brain tissues severity clinical scores decreased significantly ca074treated mice compared eae control mice moreover percentage cd4+tbet+ cxcr5+tbet+ cd4+stat4+ cd4+il17a+ cxcr5+il17a+ cd4+rort+ ccr6+rort+ cd4+tnf+ cd4+il22+ ccr6+il22+ cells decreased cd25+foxp3+ increased ca074treated eae mice compared vehicletreated eae mice ca074treated eae mice downregulated cathepsin b protein expression associated decreased tbet il17a rort il22 mrna protein expression results suggest cathepsin b novel therapeutic candidate treatment mspmid35122866 doi101016 jexpneurol2022113997,1.0
neuroradiological differentiation white matter lesions patients multiple sclerosis fabry disease abstractobjectivewhite matter lesions wml multiple sclerosis ms differ vascular wml caused fabry disease fd however atypical cases discrimination can difficult may vary individual raters aim study evaluate interrater reliability wml differentiation ms fd patientsmaterials methodsbrain mri scans 21 patients genetically confirmed fd compared 21 matched patients ms pseudonymized axial flair sequences assessed 6 blinded raters attributed either ms fd group investigate interrater reliability additionally localization wml compared two groupsresultsthe median age patients 46 years iqr 3558 interrater reliability moderate fleiss kappa 045 95ci 03059 overall 85 ratings ms group 75 fd group correct however 38 patients ms 33 patients fd correctly identified 6 raters wml involving corpus callosum p 0001 well juxtacortical p 0001 infratentorial lesions p 003 frequently observed ms patientsconclusioninterrater reliability regarding visual differentiation wml ms vascular wml fd standard axial flair images alone moderate despite distinctive features lesions group,0.0
relationship social capital quality life among adult stroke patients crosssectional study anhui province china abstractobjectivesfew studies investigated association social capital quality life qol among stroke patients address research gap aimed explore association social capital qol among stroke patients anhui province chinastudy designcrosssectional studymethodsthis crosssectional study conducted using multistage stratified random sampling method following data including demographic characteristics healthrelated conditions five dimensions social capital status quality life qol collected using questionnaire generalized linear models used determine relationship social capital qol adjusting confounding factorsresultsa total 390 participants included final analysis study results indicated subjects higher social capital including social connection coefficient 2828 95 ci 19393716 social support coefficient 2117 95 ci 10633171 trust coefficient 1346 95 ci 2732419 reciprocity coefficient 2556 95 ci 15973515 cohesion coefficient 1930 95 ci 9902870 increased odds reporting poor qol compared lower social capital group also observed association social capital qol varied across citiesconclusionsour findings show social capital associated qol adult stroke patients suggesting social capital may significant enhancing qol among adults stroke,0.0
white matter damage due vascular tau tdp43 pathologies relevance cognition abstractmulticompartment modelling white matter microstructure using neurite orientation dispersion density imaging noddi can provide information white matter health neurite density index free water measures hypothesized cerebrovascular disease alzheimers disease tdp43 proteinopathy associated distinct noddi readouts white matter damage informative identifying substrate cognitive impairment identified two independent cohorts multishell diffusion mri amyloid tau pet cognitive assessments specifically populationbased cohort 347 elderly randomly sampled olmsted county minnesota population clinical researchbased cohort 61 amyloid positive alzheimers dementia participants observed increase free water decrease neurite density using noddi measures genu corpus callosum associated vascular risk factors refer vascular white matter component tau pet signal reflective 3r 4r tau deposition associated worsening neurite density index temporal white matter measured parahippocampal cingulum inferior temporal white matter bundles worsening temporal white matter neurite density associated antemortem confirmed fdg tdp43 signature postmortem neuropathologic data small subset sample lend support findings communitydwelling cohort vascular disease prevalent noddi vascular white matter component explained variability global cognition partial r2 free water neurite density 83 mmse performance 82 comparable amyloid pet 74 global cognition 66 memory ad dementia cohort tau deposition greatest contributor cognitive performance 96 also nontrivial contribution temporal white matter component 85 cognitive performance differences observed two cohorts reflective distinct clinical composition white matter microstructural damage assessed using advanced diffusion models may add significant value distinguishing underlying substrate whether cerebrovascular disease versus neurodegenerative disease caused tau deposition tdp43 pathology cognitive impairment older adultsgraphical abstract,0.0
altered central blood glutathione alzheimers disease mild cognitive impairment metaanalysis background increasing evidence implicates oxidative stress os alzheimer disease ad mild cognitive impairment mci depletion brain antioxidant glutathione gsh may important osmediated neurodegeneration though studies postmortem brain gsh changes ad inconclusive recent vivo measurements brain blood gsh may shed light gsh changes earlier diseaseaimto quantitatively review vivo gsh ad mci compared healthy controls hc using metaanalysesmethodstudies vivo brain blood gsh levels mci ad hc group identified using medline psychinfo embase 1947june 2020 standardized mean differences smd 95 confidence intervals ci calculated outcomes using random effects models outcome measures included brain gsh meshchergarwood point resolved spectroscopy megapress versus nonmegapress blood gsh intracellular versus extracellular ad mci q statistic eggers test used assess heterogeneity risk publication bias respectivelyresultsfor brain gsh 4 ad ad135 hc223 4 mci mci213 hc211 studies included blood gsh 26 ad ad1203 hc1135 7 mci mci434 hc408 studies included brain gsh overall differ ad mci compared hc however subgroup studies using megapress reported lower brain gsh ad smd 95ci 145 183 106 p0001 mci 115 171 059 z40 p0001 ad lower intracellular extracellular blood gsh overall 087 1 30 044 z396 p0001 subgroup analysis intracellular gsh lower mci 066 111 021 p0025 heterogeneity observed throughout i2 85 fully accounted subgroup analysis eggers test indicated risk publication biasconclusionblood intracellular gsh decrease seen mci intra extracellular decreases seen ad brain gsh decreased ad mci subgroup analysis potential bias heterogeneity suggest need measurement standardization additional studies explore sources heterogeneity,0.0
measuring axial length eye magnetic resonance brain imaging background metrics derived human eye increasingly used biomarkers endpoints studies cardiovascular cerebrovascular neurological disease context important account potential confounding can arise differences ocular dimensions individuals example differences globe sizemethodswe measured axial length geometric parameter describing eye size t2weighted brain mri scans using three different image analysis software packages mango itk carestream compared results biometry measurements specialized ophthalmic instrument iolmaster 500 reference standardresultsninetythree healthy research participants mean age 510 sd 54 years analyzed level agreement mriderived measurements reference standard described mean differences follows mango 08 mm itk 05 mm carestream 01 mm upper lower 95 limits agreement across three tools ranged 09 mm 26 mm interrater reproducibility 003 mm 045 mm icc 065 093 intrarater repeatability 00 mm 02 mm icc 090 095 conclusionswe demonstrate axial measurements eye derived brain mri within 35 reference standard globe length 241 mm however limits agreement considered clinically significant axial length eye obtained mri replacement precision biometry absence biometry provide sufficient accuracy act proxy recommend measuring eye axial length mri studies biometry use retinal imaging study neurodegenerative changes control differing eye size across individuals,0.0
potential influencing factors aortic diameter specific segments population cardiovascular risk background aortic diameter critical parameter diagnosis aortic dilated diseases aortic dilation common risk factors cardiovascular diseases study aimed investigate potential influence traditional cardiovascular risk factors measures subclinical atherosclerosis aortic diameter specific segments among adultsmethodsfour hundred eight patients cardiovascular risk factors prospectively recruited observational study comprehensive transthoracic mmode 2dimensional doppler echocardiographic studies performed using commercial clinical diagnostic ultrasonography techniques aortic dimensions assessed different levels 1 annulus 2 midpoint sinuses valsalva 3 sinotubular junction 4 ascending aorta level largest diameter 5 transverse arch including proximal arch mid arch distal arch 6 descending aorta posterior left atrium 7 abdominal aorta just distal origin renal arteries multivariable linear regression analysis used evaluating aortic diameterrelated risk factors including common cardiovascular risk factors comorbidities subclinical atherosclerosis lipid profile hematological parametersresultssignificant univariate relations found aortic diameter different levels traditional cardiovascular risk factors carotid intimamedia thickness significantly correlated diameter descending abdominal aorta multivariate linear regression showed potential effects age sex body surface area cardiovascular risk factors aortic diameter enlargement among highdensity lipoprotein cholesterol significantly positive effect diameter ascending abdominal aorta diastolic blood pressure observed positive associations diameters five thoracic aortic segments systolic blood pressure independently related mid arch diameterconclusionaortic segmental diameters associated diastolic blood pressure highdensity lipoprotein cholesterol atherosclerosis diseases traditional cardiovascular risk factors determinants still need clarified better understanding aortic dilation diseases,0.0
testretest reliability performancebased outcome measures among individuals arthrogryposis multiplex congenita background individuals arthrogryposis multiplex congenita rare condition characterized joint contractures 2 body regions foot ankle involvement leading compromised gait balance purpose study establish betweendays testretest reliability performancebased outcome measures evaluating gait balance ie 10m walk test figureof8 walk test 360degree turn test modified four square step test among adolescents adults arthrogryposis multiplex congenitamethodsthis reliability study included ambulatory participants aged 10 50 years medical diagnosis arthrogryposis multiplex congenita participants completed performancebased measures randomized order two separate occasions intraclass correlation coefficients 95 confidence intervals minimal detectable changes 90 95 confidence level calculatedresultsparticipants included 38 communityambulators median 13 14 upper lower joint regions affected intraclass correlation coefficient point estimates 95 confidence intervals ranged 8597 7098 respectively minimal detectable changes 10 39 sample means largest modified four square step testconclusionsamong individuals arthrogryposis gait speed per 10m walk test well nonlinear walking dynamic balance assessment per figureof8 walk 360 degree turn tests adequate testretest reliability enabling evaluation individual patient changes changes groups ambulatory individuals arthrogryposis multiplex congenita may reliably evaluated studied outcome measures,0.0
serum metabolic profiles metal levels patients multiple sclerosis patients neuromyelitis optica spectrum disorders nmr spectroscopy icpms studies abstractbackground objectives neuromyelitis optica spectrum disorder nmosd disease misdiagnosed multiple sclerosis ms hypothesized serum metabolic profile helpful differentiation diseases early stagemethods included controls patients ms diagnosed according mcdonald criteria 2010 patients nmosd diagnosed according criteria 2015 blood samples collected clots participants overnight overfasting obtained metabolic profiles using proton magnetic resonance spectroscopy 1hnmr serum hydrophilic hydrophobic compounds serum metal levels measured using isotopespecific detection mass spectrometry icpms statistical analyses used anova tests multivariate analysis mva orthogonal partial least square discriminant analysis oplsda results analyzed metabolite levels patient groups compared controls observed significantly different levels ten metabolite signals patients ms vs controls eighteen metabolite signals patients nmsod vs controls observed significantly different levels five signals patients ms vs nmosd mva analysis patient groups indicated compounds differentiated groups compounds involved cycles connected inflammation process oxidative stress results metallomics studies confirmed metal participation processesdiscussion possible distinguish patients ms nmosd controls using anova mva tests chosen metabolite profile analyses might possibly helpful distinguishing two diseases seronegative radiologically negative cases,0.0
thrombotic microangiopathy transiently positive direct coombs test adult poststreptococcal acute glomerulonephritis case report background date case reports described association poststreptococcal acute glomerulonephritis psagn hemolytic anemia thrombocytopenia without pathology similar thrombotic microangiopathy tma however detailed mechanism leading complication tma psagn patients remains clarified contrast infection neuraminidaseproducing streptococcus pneumoniae wellknown cause tma reported transient positivity direct coombs test observed 90 patientscase presentationa 44yearold man hospitalized acute nephritic syndrome 3 weeks developing pharyngitis psagn suspected owing low complement c3 increased antistreptolysino serum creatinine 546 mg dl hematuria proteinuria throat antigen test group streptococcus positive developed hemolytic anemia thrombocytopenia hospital day 9 tma suspected owing minimal coagulation abnormalities adamts13 activity normal whereas direct coombs test transiently positive renal biopsy demonstrated glomerular endocapillary proliferation without crescents severe tubulitis peritubular capillaritis light microscopy immunofluorescence demonstrated c3 deposition along glomerular capillary walls many subepithelial humps observed electron microscopy deposition nephritisassociated plasmin receptor naplr nephritogenic protein streptococcus pyogenes observed glomeruli thus histological diagnosis typical psagn atypical severe tubulointerstitial lesions positive direct coombs test often observed pneumococcal tma patients attributed exposure thomsenfriedenreich t antigen neuraminidase streptococcus pyogenes one neuraminidaseproducing bacteria streptococcus pneumoniae tantigen exposure analyzed renal tissue patient using labelled peanut lectin probe strong specific binding affinity tantigen exposure tantigen found tubular epithelial cells small vessels tubulointerstitial area glomeruli patientconclusionthese findings suggest 2 pathogenic proteins streptococcus pyogenes ie naplr neuraminidase induced glomerular lesions psagn tubulointerstitial inflammation tma respectively resulting severe acute kidney injury patient,0.0
national multicenter study germany assess implementation infusion management treatment satisfaction quality life ms patients receiving alemtuzumab abstractbackground alemtuzumab anticd52 antibody approved treatment relapsing remitting multiple sclerosis rrms summary product characteristics smpc provides recommendations administration alemtuzumab prevent reduce risk serious side effects associated alemtuzumab infusion including myocardial ischemia hemorrhagic stroke arterial dissection pulmonary alveolar hemorrhage however realworld implementation alemtuzumab infusion management recommendations previously assessedmethods provide largescale multicenter outpatient observational study alemtuzumab infusion management daily clinical care germany alemll08025 infusems nisno 364 parameters infusion management including infusion administration clinical laboratory monitoring assessed compared study centers occurrence infusionassociated reactions iars documented moreover tsqm msis29 questionnaires used quantify patient satisfaction healthrelated quality liferesults 140 rrms patients enrolled study alemtuzumab infusion regimes treatment course 1 2 comparable infusion sites accordance recommendations smpc standardization infusion management associated satisfactory safety profile iars usually mild headache 136 rash 107 pyrexia 64 common ones tsqm msis29 scores denoted high patient satisfaction healthrelated quality life among rrms patients treated alemtuzumabconclusion conclusion results indicate infusion management alemtuzumab highly standardized line smpc alemtuzumab treatment implementation infusion management recommendations associated satisfactory safety profile regarding occurrence iars high patient satisfaction healthrelated quality life important indicators quality ms care,0.0
t h 17 cells multiple sclerosis dislodge another brick wall sci immunol 2022 feb 4 7 68 eabo2989 doi 101126 sciimmunolabo2989 epub 2022 feb 4abstract figure see text pmid35119940 doi101126 sciimmunolabo2989,0.0
disentangling glial diversity peripheral nerves singlenuclei resolution nat neurosci 2022 feb 3 doi 101038 s41593021010051 online ahead printabstractthe peripheral nerve contains diverse cell types support proper function maintenance study analyzed multiple peripheral nerves using singlenuclei rna sequencing allowed us circumvent difficulties encountered analyzing cells complex morphologies via conventional singlecell methods resultant mouse peripheral nerve cell atlas highlights diversity cell types including multiple subtypes schwann cells scs immune cells stromal cells identified distinct myelinating sc subtype expresses cldn14 adamtsl1 pmp2 preferentially ensheathes motor axons number motorassociated pmp2+ scs reduced amyotrophic lateral sclerosis als sod1g93a mouse model human als nerve samples findings reveal diversity scs cell types peripheral nerve serve reference future studies nerve biology diseasepmid35115729 doi101038 s41593021010051,1.0
changes functional connectivity dimethyl fumarate treatment multiple sclerosis neurol ther 2022 feb 4 doi 101007 s4012002200328w online ahead printabstractintroduction despite increased availability diseasemodifying therapies dmts treating relapsingremitting multiple sclerosis rrms studies evaluated dmtassociated brain functional changesmethods investigated whether significant restingstate functional connectivity fc changes occurred rrms patients 6 12 months dimethyl fumarate dmf treatment using seedbased datadriven approachresults thirty patients followed 6 months therapy 27 reached 12month followup three patients baseline one 12 months showed gadoliniumenhancing lesions find significant fc changes therapy either time point 12 months dmf observed relatively modest brain volume loss significant improvement paced auditory serial addition test 3 s 25foot walk test scoresconclusion absence fc changes due low degree baseline inflammation patients though exclude time may required observe changes fc changes may reflect beneficial effect dmf therapy supported conventional mri findings clinical improvementpmid35119678 doi101007 s4012002200328w,0.0
neural diffusion tensor imaging metrics correlate clinical measures people relapsingremitting ms neuroradiol j 2022 feb 419714009211067400 doi 101177 19714009211067400 online ahead printabstractbackground purpose diffusion tensor imaging dti can detect microstructural changes white matter multiple sclerosis ms might clarify mechanisms responsible disability thus aimed compare dti metrics relapsingremitting ms patients rrms healthy controls hcs explore correlations dti metrics total brain white matter tbwm white matter lesion wml clinical parameters compared volumetric measuresmaterial methods 37 rrms patients 19 age sexmatched hcs included participants clinical assessments structural diffusion scans 3t mri volumetric white matter dti metrics fractional anisotropy fa mean radial axial diffusivities md rd ad estimated correlated clinical parameters mean group differences calculated using ttests univariate correlations pearson correlation coefficientsresults compared hcs statistically significant increases md +36 rd +48 ad +27 decrease fa 43 tbwm rrms observed p 01 md rd tbwm ad wml correlated moderately disability status volumetric segmentation indicated decrease total brain volume gm wm 5 reciprocal increase csf +26 rrms p 01 importantly dti parameters showed medium correlation cognitive domains contrast white matterrelated volumetric measurements rrms pearson correlation p 05 conclusions study shows correlation dti metrics clinical symptoms ms particular cognition generally findings indicated dti useful unique technique evaluating clinical features white matter disease warrants investigation clinical rolepmid35118885 doi101177 19714009211067400,0.0
monthly tripledose gadolinium administration potential associations leukopenia hypophosphatemia bone marrow t1 hyperintensity j int med res 2022 feb 50 2 3000605221076977 doi 101177 03000605221076977abstractobjective monthly scanning tripledose gadopentetate dimeglumine shown associated progressive increases bone t1 hyperintensity hypophosphatemia leukopenia study performed retrospectively investigate potential associations among phenomenamethods retrospective analysis involved patients received monthly tripledose gadopentetate dimeglumine 2 years part treatment multiple sclerosis monthly magnetic resonance imaging scans brain n 67 segmented evaluate signal intensity cranial marrow potential associations among marrow t1 hyperintensity serum phosphate concentration white blood cell count examinedresults patients leukopenia group showed statistically significant mean monthly increase bone marrow signaltonoise ratio 00430 month patients leukopenia group showed mean monthly increase bone marrow signaltonoise ratio 00398 month statistically significant patients hypophosphatemia group significantly less likely develop leukopenia patients never developed hypophosphatemiaconclusions although monthly administration tripledose gadopentetate dimeglumine 13 months associated progressive increases leukopenia hypophosphatemia t1 signal intensity bone study showed inverse relationship leukopenia hypophosphatemiapmid35118901 doi101177 03000605221076977,0.0
blood gfap emerging biomarker brain spinal cord disorders nat rev neurol 2022 feb 3 doi 101038 s41582021006163 online ahead printabstractbloodderived biomarkers brain spinal cord diseases urgently needed introduction highly sensitive immunoassays led rapid increase number potential bloodderived biomarkers diagnosis monitoring neurological disorders 2018 fda authorized blood test clinical use evaluation mild traumatic brain injury tbi test measures levels astrocytic intermediate filament glial fibrillary acidic protein gfap neuroaxonal marker ubiquitin carboxyterminal hydrolase l1 tbi blood gfap levels correlated clinical severity extent intracranial pathology evidence also indicates blood gfap levels hold potential reflect might enable prediction worsening disability individuals progressive multiple sclerosis growing body evidence suggests blood gfap levels can used detect even subtle injury cns importantly successful completion ongoing validation pointofcare platforms blood gfap might ameliorate decision algorithms acute neurological diseases tbi stroke important economic implications review provide systematic overview evidence regarding utility blood gfap biomarker neurological diseases propose model gfap concentration dynamics different conditions discuss limitations hamper widespread use gfap clinical setting opinion clinical use blood gfap measurements potential contribute accelerated diagnosis improved prognostication represents important step forward era precision medicinepmid35115728 doi101038 s41582021006163,0.0
neuron oligodendrocyte precursor cell synapses protagonists oligodendrocyte development myelination targets therapeutics front neurosci 2022 jan 18 15779125 doi 103389 fnins2021779125 ecollection 2021abstractthe development neuronal circuitry required cognition complex motor behaviors sensory integration requires myelination role glial cells astrocytes microglia shaping synapses circuits covered reviews journal elsewhere review summarizes role another glial cell type oligodendrocytes shaping synapse formation neuronal circuit development myelination normal development demyelinating disease oligodendrocytes ensheath insulate neuronal axons myelin facilitates fast conduction electrical nerve impulses via saltatory conduction oligodendrocytes also proliferate postnatal development defects maturation linked abnormal myelination myelination also regulates timing activity neural circuits important maintaining health axons providing nutritional support recent studies shown dysfunction oligodendrocyte development myelination can contribute defects neuronal synapse formation circuit development discuss glutamatergic gabaergic receptors voltage gated ion channel expression function oligodendrocyte development myelination explain role excitatory inhibitory neurotransmission oligodendrocyte proliferation migration differentiation myelination focus understanding synaptic connectivity neurons opcs can inform future therapeutics demyelinating disease discuss gaps literature inform new therapies remyelinationpmid35115904 pmcpmc8804499 doi103389 fnins2021779125,1.0
onychomycosis caused kloeckera apiculata case report patient multiple sclerosis skin appendage disord 2022 jan 8 1 4952 doi 101159 000518046 epub 2021 aug 13abstractwe report first case onychomycosis caused kloeckera apiculata woman multiple sclerosis videodermoscopic examination showed spiked pattern distal irregular aspect colonies sabouraud agar white creamy smooth microscopic examination showed blastoconidia malditof confirmed kloeckera apiculata causal agentpmid35118131 pmcpmc8787566 doi101159 000518046,0.0
intertwined like double helix metasynthesis qualitative literature examining experiences living someone multiple sclerosis health expect 2022 feb 4 doi 101111 hex13432 online ahead printabstractbackground multiple sclerosis ms chronic serious condition uncertain course outcome relatively little literature experiences people live person ms inhabit locus care spans caring relational act caring moral stance addressing fairness compassion justice person msmethods using theoretical lens personhood undertook scoping review metasynthesis qualitative literature experiences people live person ms focusing nature constraints upon caringresults 330 articles 49 included review identified five themes one theseseeking information supportreflects political economy care two concerned moral domain care caring labour living uncertainty final two themeschanging identities adapting life person mspoint negotiation reconstitution personhood person ms people live withconclusion people ms embedded relational social networks partners family friends fundamental support personhood people live coconstituents patients identity assisting make sense world self times disruption due illness support services health care professionals caring people ms currently much patientcentred young people particular report roles elided health systems interaction parent ms need look beyond person ms recognize relational network people surround broaden focus encompass networkpatient public involvement research team includes four members ms two members lived experience living working people ms third person team member lives partner ms provided feedback paperpmid35118764 doi101111 hex13432,0.0
antiinflammatory proautophagy effects cannabinoid receptor cb2r possibility modulation type 1 diabetes front pharmacol 2022 jan 18 12809965 doi 103389 fphar2021809965 ecollection 2021abstracttype 1 diabetes mellitus t1dm autoimmune disease resulting loss insulinsecreting cells islets langerhans loss cells initiated selftolerance cellderived contents breaks leads t cellmediated cell damage ultimately cell apoptosis many investigations demonstrated positive effects antagonizing cannabinoid receptor 1 cb1r metabolic diseases fatty liver disease obesity diabetes mellitus role cannabinoid receptor 2 cb2r diseases relatively unknown activation cb2r known immunosuppressive roles multiple sclerosis rheumatoid arthritis crohns celiac lupus diseases since autoimmune diseases can share common environmental genetic factors propose cb2r specific agonists may also serve disease modifiers diabetes mellitus cnr2 gene encodes cb2r protein result gene duplication cnr1 encodes cb1r protein ortholog evolved rapidly transitioning invertebrates vertebrate hundreds million years ago human specific cnr2 isoforms induced inflammation pancreatic islets cnr2 nonsynonymous snp q63r associated autoimmune diseases collected evidence literature studies demonstrating cb2r involved regulating inflammasome especially release cytokine interleukin 1b il1 furthermore cb2r activation controls intracellular autophagy may regulate secretion extracellular vesicles adipocytes participate recycling lipid droplets dysregulation induces chronic inflammation obesity cb2r activation may play similar role islets langerhans will discuss future strategies unravel roles cb2r modifiers potentially play t1dmpmid35115945 pmcpmc8804091 doi103389 fphar2021809965,0.0
different bloodbrainbarrier disruption profiles multiple sclerosis neuromyelitis optica spectrum disorders neuropsychiatric systemic lupus erythematosus neurol neurochir pol 2022 feb 4 doi 105603 pjnnsa20220013 online ahead printabstractaim study assess differences bbb damage profiles measuring serum levels soluble vascular cell adhesion molecule1 svcam1 soluble platelet endothelial cell adhesion molecule1 specam1 soluble intercellular adhesion molecule1 sicam1 s100 calciumbinding protein b s100b relapsingremitting multiple sclerosis rrms neuromyelitis optica spectrum disorders nmosd neuropsychiatric systemic lupus erythematosus npsle patientsclinical rationale study bloodbrainbarrier bbb disruption one key pathological processes involved various demyelinating diseases central nervous system cns associated shedding cell adhesion molecules s100b serum compartment therefore making assessment serum levels abovementioned molecules provide information disease pathogenesis severity bbb disruption disease activitymaterial methods recruited 42 rrms 19 nmosd 35 npsle patients subjects treated betainterferons glatiramer acetate rrms oral steroids azathioprine nmosd npsle immunosuppressants npsle antimalarials npsle clinical condition patients assessed using kurtzke expanded disability status scale ms nmosd systemic lupus erythematosus disease activity index npsle serum levels svcam1 specam1 sicam1 s100b determined using enzymelinked immunosorbent assay elisa results found lowest levels specam1 sicam1 s100b sera nmosd patients highest levels specam1 sicam1 observed npsle npsle ms respectively statistically significant differences svcam1 levels examined groups ms nmosd negative correlation edss score following molecules specam1 sicam1 s100bconclusions clinical implications conclude different profile bloodbrainbarrier disruption reflected cell adhesion molecules shedding spectrum autoimmune cns disorders disseminated white matter lesions molecules become new biomarkers used cns demyelinating diseases differential diagnoses monitoring disease activity studies larger groups patients necessarypmid35118639 doi105603 pjnnsa20220013,1.0
uncovering patterns realworld psychological support seeking patient experience multiple sclerosis abstractbackgroundwith rate psychological disorder disproportionately high people multiple sclerosis pwms important receive adequate psychological support informal formal sources psychological support ms available paucity research understanding actual pattern support pwms interact realworld context aimed understand examining pattern access across different sources psychological support large cohort pwms experiences support received also explore context different ms symptom profiles demographicsmethodin online survey asked 565 pwms report actual pattern usage experience receiving psychological support four key sources friends family peers ms organisations charities ms specialist nurses mental health professionals demographic clinical data also gathered ms profile symptomsresultsfriends family peers rated common helpful easy access source psychological support however participants received psychological support multiple sources almost always conjunction support friends family peers demographic ms related factors predicted whether patients access source younger pwms recently diagnosed likely avail support friend family peers patients bothered symptoms likely avail psychological support sources particular pwms bothered fatigue psychological symptoms likely avail support mental health professionals overall helpfulness support depended largely well support provider knew pwms person ms condition well level emotional practical skills support providedconclusionpeople ms need access multiple sources support meet full spectrum psychological needs needed friends family peers mental health professionals emotional support ms organisations charities specialist ms nurses learning skills manage ms points towards need take collaborative approach amongst different sources support ensure needs can effectively met,0.0
tlr9 regulates nlrp3 inflammasome activation via nfkb signaling pathway diabetic nephropathy background tolllike receptors tlrs critical sensors conservation bacterial molecules play key role host defense pathogens effect tlrs maintenance diabetic nephropathy dn resistance infection investigated however detailed effects tlr9 dn development remain elusivemethodswe performed quantitative reverse transcriptionpolymerase chain reaction western blotting detect tlr9 expression levels kidneys experimental mice db db highglucosetreated mouse mesangial cell strains mcs resultstlr9 expression found remarkably upregulated kidneys experimental mice db db mcs cultivated hyperglycemic conditions moreover knockdown tlr9 restrain nfkb viability downregulate nlrp3 inflammasome high glucosetreated mcs tlr9 inhibition also alleviated inflammation apoptosis reversed addition nfb activator betulinic acid furthermore depleted tlr9 levels restrained nfb viability nlrp3 expression reduced kidney inflammation microalbuminuria discharge blood sugar level glomerular damage experimental mice db db kidneys conclusionsthese findings offer novel insights regulation tlr9 via nuclear factorkb nod lrr pyrin domaincontaining protein 3 inflammasome inflammation pathways dn progression,0.0
interactions selected cardiovascular active natural compounds cxcr4 cxcr7 receptors molecular docking molecular dynamics pharmacokinetic#x2f toxicity prediction study background chemokine cxcl12 two receptors cxcr4 cxcr7 involved inflammation hematopoietic cell trafficking study designed investigate molecular docking interactions four popular cardiovascularactive natural compounds curcumin resveratrol quercetin eucalyptol receptors predict druglike properties hypothesize compounds can modify cxcl12 cxcr4 cxcr7 pathway offering benefits coronary artery disease patientsmethodsdocking analyses carried characterized molecular environment moe software protein data bank http wwwrcsborg retrieved protein structure generation crystal structures cxcr4 cxcr7 receptors pdb code 3odu 6k3f active sites receptors evaluated extracted full protein molecular docking protocol done compounds presented parameters included docking scores ligand binding efficiency hydrogen bonding pharmacokinetic toxic properties adme t calculated using swissadme protoxii predherg softwares predict druglike properties compounds thermochemical molecular orbital analysis molecular dynamics simulations also doneresultsall compounds showed efficient interactions cxcr4 cxcr7 receptors docking scores toward proteins 3odu cxcr4 6k3f cxcr7 771 717 curcumin 597 603 quercetin 568 549 transresveratrol 488 470 1 s 4 s eucalyptol respectively indicating compounds except quercetin interactions cxcr4 cxcr7 structurally functionally important residues interactive sites docked cxcr4complex cxcr7complex identified adme analysis showed compounds druglike properties 1 s 4 s eucalyptol potential weak cardiotoxicity results thermochemical molecular orbital analysis molecular dynamics simulation validated outcomes molecular docking studyconclusionscurcumin showed top binding interaction active sites cxcr4 cxcr7 receptors best safety profile followed quercetin resveratrol eucalyptol compounds demonstrated druglike properties eucalyptol promising potential can used inhalation skin massage knowledge first attempt find binding interactions natural agents cxcr4 cxcr7 receptors predict druggability,0.0
urine neopterin childhood acute demyelinating diseases potential differential diagnosis abstractinflammatory demyelinating diseases central nervous system cns childhood include clinically radiologically defined diseases acute disseminated encephalomyelitis adem multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd myelin oligodendrocyte glycoprotein antibodyassociated disorder mogad differentiation phenotypes can difficult cases meeting established diagnostic criteria may remain without specific diagnosis months laboratory markers can assist diagnosis management diseases previous studies suggest serum kynureninetryptophan pathway products serum neopterin biomarkers cns autoimmune diseases urine reliable repeatable source analysis products additional advantage easy sampling measured neopterin concentrations serum urine samples urinary biopterin serum kynureninetryptophan levels autoimmune demyelinating diseases cns pediatric multiple sclerosis pms n27 mogad n10 nmosd n5 patients control group consisting healthy children children noninflammatory diseases n13 total 55 children methods high performance liquid chromatography hplc neopterin biopterin creatinine urine kynurenine tryptophan serum elisa used serum neopterin comparison biomarkers diagnostic groups showed urinary neopterin values significantly higher pms group p0002 cutoff point determined roc analysis indicated urinary neopterin 16775mol mol creatinine distinguish patients controls sensitivity 71 specificity 90 significant difference pms control groups p0002 difference observed pms patients relapse stable state therefore urinary neopterin appeared potential marker differentiate pms demyelinating patient groups mogad nmosd well controls fact pteridine pathway products studied urine serum children demyelinating disease highlights novelty study research larger samples confirm present results molecules might assist differential diagnosis pms demyelinating cns diseases,1.0
clinical language search algorithm freetext facilitating appropriate imaging background comprehensiveness maintenance american college radiology acr appropriateness criteria ac makes unique resource evidencebased clinical imaging decision support underutilized clinicians facilitate use imaging recommendations develop natural language processing nlp search algorithm automatically matches clinical indications physicians write imaging orders appropriate ac imaging recommendationsmethodswe apply hybrid model semantic similarity sent2vec model trained 223 million scientific sentences combined term frequency inverse document frequency features ac documents ranked based embeddings cosine distance query model testing compiled dataset simulated simple complex indications ac document n 410 another clinical indications randomly sampled radiology reports n 100 compare algorithm custom google search engineresultson simulated indications algorithm ranked ground truth documents top 3 98 simple queries 85 complex queries similarly randomly sampled radiology report dataset algorithm ranked 86 indications single match top 3 vague distracting phrases present freetext indications main sources errors algorithm provides relevant results custom google search engine especially complex queriesconclusionswe developed evaluated nlp algorithm matches clinical indications appropriate ac guidelines approach can integrated imaging ordering systems automated access guidelines,0.0
early predictive risk factors dimethyl fumarateassociated lymphopenia patients multiple sclerosis abstractbackgroundlymphopenia major concern ms patients treated dimethylfumarate dmf increases risk progressive multifocal leukoencephalopathy pronounced reduction absolute lymphocyte counts alcs early treatment initiation suggested associated occurrence lymphopenia thereafterobjectivesto identify risk factors dmfinduced lymphopenia evaluate whether degree decrease alcs three months initiation dmf treatment predictor subsequent development lymphopeniamethodsin realworld spanish prospective multicenter study conducted ms patients started dmf 2014 2019 analyzed association dmfrelated lymphopenia percentage early alcs decline using regression models considering significant lymphopenia grades 2+3 severe lymphopenia grade 3 cutoff values early alcs declines obtained using roc curveresultsamong 532 ms patients treated dmf 193 363 developed grade lymphopenia older age lower alcs treatment onset predicted risk lymphopenia best predictive risk factor reduction alcs within three first months treatment specifically reduction alcs212 associated 65fold higher risk developing significant lymphopenia decrease alcs402 127fold higher risk developing severe lymphopeniaconclusionsa pronounced reduction alcs early initiation dmf ms patients best predictive risk factor subsequent development significant lymphopenia,0.0
association microglial activation serum kynurenine pathway metabolites multiple sclerosis patients abstractbackgroundmicroglial activation associates ms progression unclear drives persistent proinflammatory state metabolites kynurenine pathway kp main metabolism route tryptophan can influence function brain innate immune cellsobjectiveto investigate whether tryptophan metabolites blood associate tspopet measurable microglial activation ms brainmethodsmicroglial activation detected using pet imaging tspobinding radioligand 11c pk11195 distribution volume ratios dvr specific 11c pk11195binding normal appearing white matter nawm lesions thalamus calculated ultrahigh performance liquid chromatographytandem mass spectrometry used measure serum levels tryptophan kynurenine pathway metabolitesresultsthe study cohort consisted 48 ms patients increased dvr nawm thalamus correlated decreased serum 3hydroxykynurenine level r 031 p0031 r032 p0028 increased edss correlated decreased 3hydroxykynurenine xanthurenic acid r 036 p0012 r031 p0034 increased dvr nawm thalamus r033 p0023 r034 p0020 respectively conclusionsthis clinical study demonstrates association low serum 3hydroxykynurenine high microglial activation ms investigations warranted elucidation biological mechanisms behind association,0.0
incidence prevalence characteristics heart failure among patients multiple sclerosis systematic review metaanalysis abstractintroductionmultiple sclerosis ms common neurological autoimmune disease although primarily harms central nervous system organs liable affected well growing body evidence suggesting heart failure considered potential suspect cardiac dysfunction insufficiency among ms patients designed systematic review metaanalysis elaborate incidence prevalence characteristics hf among ms patientsmethodswe conducted systematic computerized search using four data banks pubmed medline scopus web science embase via elsevier literature search found 930 articles eliminating duplicates 695 articles remained 42 articles assessed inclusion eligibility eventually 8 fulltext articles included final data extraction tableresultsthe overall prevalence heart failure 1 95 ci 06 15 ranged 06 observed uk 18 taiwan study overall incidence heart failure also 07 95 ci 04 12 ranging 02 observed uk 14 usa pooled odds ratio association heart failure multiple sclerosis calculated based 4 studies using random effect model 129 95 ci 074226 i2825 significantconclusionin conclusion study demonstrates patients ms elevated risk developing heart failure compared general population highlights importance regular thorough checkups pwms effort better detect cardiovascular abnormality dysfunction disease soon possible help improve prognosis,0.0
unusual neurologic manifestations vogtkoyanagiharada disease systematic literature review background purposethe usual neurologic manifestations vogtkoyanagiharada vkh disease include aseptic meningitis headaches performed present study review unusual neurologic manifestations reported vkh disease summarize themmethodsa literature search performed english language scopus medline via pubmed 1946 july 31 2021 using following terms vogt koyanagi harada disease vkh disease brain spinal cord cns central nervous system neurologic peripheral nervous system polyneuropathies inclusion criteria unusual neurologic manifestations vkh diseaseresultsour literature search yielded 417 total articles pubmed 334 scopus 83 32 studies comprising 43 patients 22 men 21 women 628 younger 50 years included systematic literature review regarding study design studies case reports published 1981 2021 cns involvement reported 93 vkh disease peripheral nervous system involvement represents 7 cases cerebral lesions parenchymal inflammatory lesions white matter posterior fossa contrast enhancement 163 leptomeningitis 93 pachymeningitis 7 meningoencephalitis 23 ischemic stroke 46 hemorrhagic stroke 23 transient ischemic attack 23 hydrocephalus 23 optic nerve lesions anterior ischemic optic neuropathy 209 optic neuritis 93 concerning spinal cord lesion mainly myelitis 14 conclusionthis systematic literature review provides summary different unusual neurologic manifestations reported vkh disease,0.0
therapeutic options premature ovarian insufficiency updated review abstractprimary ovarian insufficiency poi rare gynecological condition disease causes menstrual disturbances infertility various health problems historically hormone replacement therapy firstline treatment disorder women diagnosed poi left limited therapeutic options order remedy situation new generation therapeutic approaches vitro activation mitochondrial activation technique stem cell exosomes therapy biomaterials strategies plateletrich plasma intraovarian infusion developed however emerging therapies yet experimental stage require precise design components accelerate conversion clinical treatments thus medical practitioner bears responsibility selecting suitable therapies individual patients article provide timely analysis therapeutic strategies available poi patients discuss prospects poi therapy,0.0
epidemiological study multiple sclerosis illawarra region intern med j 2022 feb 3 doi 101111 imj15704 online ahead printabstractbackground multiple sclerosis ms autoimmune inflammatory demyelinating disease causes significant disabilities latest ms epidemiological data australia reveals rising prevalence epidemiological study ms conducted far illawarra regionaim calculate prevalence incidence ms illawarra compare regions states national prevalence datamethod data ms patients illawarra collected hospital medical records ambulatory care units hospital pharmacy prevalence calculated alive ms patients june 30 2018 expressed per 100 000 population yearly adjusted incidence rate calculated 10 years 20092019 expressed cases per 100 000 populationyearsresults estimated ms prevalence illawarra 1166 per 100 000 population yearly incidence 20092019 506 cases per 100 000 populationyears female male 31 relapsingremitting ms rrms common type 277 397 697 primary progressive ms ppms 52 397 13 secondary progressive ms spms 45 397 113 unknown 23 commonest age diagnosis ranged 3039 years types rrms ppms 3039 years 4049 years respectively commonly recorded treatment natalizumab 103 patients followed fingolimod 82 patients interferon 58 patients conclusion calculated ms prevalence illawarra higher nsw australian average ms prevalence epidemiological studies focusing ms risk factors factors bearing ms prevalence illawarra required article protected copyright rights reservedpmid35112760 doi101111 imj15704,1.0
frequency ocular manifestations multiple sclerosis patients admitted tertiary care hospital saudi arabia eur rev med pharmacol sci 2022 jan 26 2 637642 doi 1026355 eurrev_202201_27890abstractobjective multiple sclerosis ms one destructive demyelinating diseases nervous system manifests broad involvement visual system present study aimed evaluate frequency ocular symptoms among ms patients admitted kingdom hospital saudi arabia patients methods crosssectional study aiming investigating prevalence eye disease among ms patients referred hawtat sudair hospital zulfi general hospital majmaah general hospital kingdom hospital riyadh saudi arabia january 2020 december 2020 sample size made 100 ms patients including 50 males 50 females presented eye disorders data analyzed spss 25 chisquare test descriptive statisticsresults examined patients included 100 patients ms symptoms aged 35 years ranging 20 70 years results showed considerable lack sharpness vision among patients 80 rate double vision reported 49 among prevalent vision problem onset disease examination timeconclusions achieved data study demonstrated multiple sclerosis cause eye diseases initial recognition syndrome provides possibility appropriate evaluation patients clinicians moreover prevalence ms ocular symptoms may occur consequentlypmid35113439 doi1026355 eurrev_202201_27890,1.0
indepth characterization somatic orofacial sensitive dysfunctions interferingsymptoms relapsingremitting experimental autoimmune encephalomyelitis mouse model front neurol 2022 jan 17 12789432 doi 103389 fneur2021789432 ecollection 2021abstractamong many symptoms motor sensory cognitive associated multiple sclerosis ms chronic pain common disabling condition particular neuropathic pain symptoms prevalent debilitating even early stages disease unfortunately chronic pain still lacks efficient therapeutic agents progress needed clinically better characterizing pain symptoms ms understanding underlying mechanisms ii preclinically developing closely dedicated model identify new therapeutic targets evaluate new drugs setting new variants experimental autoimmune encephalomyelitis eae currently developed mice exhibit less severe motor impairments thereby avoiding confounding factors assessing pain behaviors disease course among optimized relapsingremitting eae quilaeae mouse model induced using myelin oligodendrocyte glycoprotein peptide fragment 3555 pertussis toxin quillaja bark saponin seems promising study sought better define sensitive dysfunctions ii extend behavioral characterization interfering symptoms often associated pain ms mood disturbances fatigue cognitive impairment optimized quilaeae model made indepth characterization optimized quilaeae model describing first time somatic thermal hyperalgesia associated mechanical cold allodynia evaluation orofacial pain sensitivity showed mechanical thermal allodynia detailed evaluation motor behaviors highlighted slight defects fine motor coordination quilaeae mice without impact pain evaluation finally anxietyrelated cognitive impairment observed peak sensitive symptoms pharmacologically previously described found pregabalin treatment commonly used neuropathic pain patients induced analgesic effect mechanical allodynia addition showed antihyperalgesic thermal effect model results demonstrate quilaeae model clearly interest studying pain symptom development used identify evaluate new therapeutic targets presence interfering symptoms still needs characterizedpmid35111128 pmcpmc8801881 doi103389 fneur2021789432,1.0
longterm outcome radiofrequency ablation multiple sclerosisrelated symptomatic trigeminal neuralgia neurosurgery 2022 jan 11 doi 101227 neu0000000000001817 online ahead printabstractbackground radiofrequency lesioning rfl used surgically manage trigeminal neuralgia tn secondary multiple sclerosis ms however longterm outcome rfl establishedobjective investigate longterm clinical outcome rfl msrelated tn symptomatic trigeminal neuralgia stn methods 23yr period institutional data available 51 patients stn underwent least one rfl procedure treat facial pain patient outcome evaluated mean followup 69 mo 95 confidence interval range 5286 mo pain medication npnm primary longterm outcome measureresults initial rfl procedure immediate pain relief achieved 50 patients 98 npnm assessed 1 3 6 yr 86 52 22 respectively last clinical visit initial rfl 23 patients 45 pain recurrence underwent repeat rfl npnm 1 3 6 yr repeat rfl 85 58 32 respectively difference pain outcome initial repeat rfl p 77 ten patients pain recurrence underwent additional rfl procedures two patients developed mastication muscle weakness one patient experienced corneal abrasion resolved early ophthalmological interventions one patient experienced bothersome numbnessconclusion rfl achieves npnm status stn can repeated similar efficacypmid35113822 doi101227 neu0000000000001817,0.0
genomic multiple sclerosis risk variants modulate expression ankrd55il6st gene region immature dendritic cells front immunol 2022 jan 17 12816930 doi 103389 fimmu2021816930 ecollection 2021abstractintronic singlenucleotide polymorphisms snps ankrd55 gene associated risk multiple sclerosis ms rheumatoid arthritis genomewide association studies gwas risk alleles linked higher expression levels ankrd55 neighboring il6st gp130 gene cd4+ t lymphocytes healthy controls biological function ankrd55 role immune system cellular sources expression lymphocytes remain uncharacterized show monocytes gain capacity express ankrd55 differentiation immature monocytederived dendritic cells modcs presence interleukin il 4 granulocytemacrophage colonystimulating factor gmcsf ankrd55 expression levels enhanced retinoic acid agonist am580 downregulated following maturation interferon ifn lipopolysaccharide lps ankrd55 detected nucleus modc nuclear speckles also analyzed adjacent il6st il31ra slc38a9 genes note healthy controls ms risk snp genotype influenced ankrd55 il6st expression immature modc opposite directions cd4+ t cells effect stronger partially correlated snp rs13186299 located similar main ms risk snps ankrd55 intron upon analysis ms patients main gwas ms risk snp rs7731626 associated ankrd55 expression levels cd4+ t cells modcspecific ankrd55 il6st mrna levels showed significant differences according clinical form disease contrast healthy controls influenced genotype also measured serum sgp130 levels found higher homozygotes protective allele rs7731626 study characterizes ankrd55 expression modc indicates monocytetodendritic cell modc differentiation process potentially influenced ms risk snpspmid35111166 pmcpmc8801523 doi103389 fimmu2021816930,0.0
b tcell responses sarscov2 vaccination patients multiple sclerosis receiving disease modifying therapies immunological patterns clinical implications front immunol 2022 jan 17 12796482 doi 103389 fimmu2021796482 ecollection 2021abstractbackground vaccination campaign contrast spread severe acute respiratory syndrome coronavirus2 sarscov2 raised issue vaccine immunogenicity special populations people multiple sclerosis pwms highly effective disease modifying treatments dmts humoral responses sarscov2 mrna vaccines well characterized general population pwms little known cellmediated responses conferring protection sarscov2 infection severe coronavirus disease2019 covid19 methods pwms ocrelizumab fingolimod natalizumab vaccinated two doses mrnabnt162b2 comirnaty vaccine enrolled antispike s antinucleoprotein n antibody titers ifngamma production upon s n peptide libraries stimulation peripheral blood lymphocyte absolute counts assessed least 1 month within 4 months vaccine second dose administration group age sex matched healthy donors hd included reference group statistical analysis performed using graphpad prism 821results thirty pwms 9 hds enrolled patients negative antin antibody detection reported previous symptoms covid19 peripheral blood lymphocyte counts assessed pwms showing reduction circulating blymphocytes pwms ocrelizumab ii reduction peripheral blood b tlymphocyte absolute counts pwms fingolimod iii normal b tlymphocyte absolute counts increase circulating cd16+cd56+ nkcells pwms natalizumab three patterns immunological responses identified pwms patients ocrelizumab antis antibody lacking reduced tcell responses normal patients fingolimod antis titers tcell mediated responses impaired patients natalizumab antis titers tcell responses present comparable observed hdconclusions evaluation tcell responses antis titers peripheral blood lymphocyte absolute count pwms dmts can help better characterize immunological response sarscov2 vaccination evaluation tcell responses longitudinal cohorts pwms will help clarify protective role preventing sarscov2 infection severe covid19 correlation dmt treatment immunological responses sarscov2 vaccines help better evaluate vaccination strategies pwmspmid35111162 pmcpmc8801814 doi103389 fimmu2021796482,0.0
closer look influence mood disability illness intrusiveness multiple sclerosis rehabil psychol 2022 feb 67 1 100109 doi 101037 rep0000393 epub 2021 oct 4abstractpurpose multiple sclerosis ms patients often report high levels illness intrusiveness direct indirect effects disability psychological symptoms illness intrusiveness remain largely unknown despite pervasiveness present study aimed examine depression anxiety can serve mechanisms disability may impact illness intrusiveness 3 life domainsinstrumental activities intimacy relationships personal developmentmethod participants n 72 adults mage 4786 sd 1179 predominantly female 736 diagnosed relapseremitting ms 819 data used archival neuropsychological database data selfreport measures analyzed examine relationship disability illness intrusiveness depression anxiety mediators mediation models run total illness intrusiveness subscalesresults depression anxiety significant mediators disability may impact overall illness intrusiveness examining life domains depression significant mediator domains anxiety significant mediator disability relationships personal developmentconclusions results suggest greater disability directly indirectly interferes illness intrusiveness via depression anxiety however life domains differentially impacted thus study helps guide interventions best symptoms target improve illness intrusiveness overall quality life psycinfo database record c 2022 apa rights reserved pmid35113641 doi101037 rep0000393,0.0
gastrointestinal motility disorders patients multiple sclerosis singlecenter study neurogastroenterol motil 2022 feb 3e14326 doi 101111 nmo14326 online ahead printabstractbackground prevalent gastrointestinal symptoms multiple sclerosis ms relate lower bowel dysfunction often association bladder manifestationsobjective assess clinical objective gastrointestinal motor dysfunctions patients msmethods singlecenter retrospective study 166 patients evaluated 1996 2020 reviewed characterization ms gastrointestinal neurological symptoms measurements gastrointestinal colonic transit anorectal manometrykey results time gastrointestinal evaluations 166 patients ms 138 women 83 111 relapsingremitting phase 52 progressive phase 3 patients disease phase assigned due insufficient data constipation identified 82 136 166 patients 103 116 88 patients bladder symptoms also constipation fecal incontinence delayed gastric emptying 4 h colonic transit 24 h identified 16 7 cohort respectively 22 accelerated gastric emptying anorectal manometry resting anal sphincter pressure 90 mm hg rectoanal pressure differential 50mm hg suggested evacuation disorder patients constipationconclusions inferences addition slow colonic transit anorectal dysfunction leading constipation ms 22 patients accelerated gastric emptyingpmid35112759 doi101111 nmo14326,0.0
paraneoplastic autoimmune encephalitides antineuronal antibodies t lymphocytes questions pathogenesis front neurol 2022 jan 17 12744653 doi 103389 fneur2021744653 ecollection 2021abstractautoimmune paraneoplastic encephalitides represent increasingly recognized cause devastating human illness well emerging area neurological injury associated immune checkpoint inhibitors two groups antibodies detected affected patients antibodies first group directed neuronal cell surface membrane proteins exemplified antibodies directed nmethyldaspartate receptor antinmdar found patients autoimmune encephalitis antibodies directed leucinerich gliomainactivated 1 protein antilgi1 associated faciobrachial dystonic seizures limbic encephalitis antibodies group produce nonlethal neuronal dysfunction associated conditions often respond treatment antibodies second group exemplified antiyo antibody found patients rapidly progressive cerebellar syndrome antihu antibody associated encephalomyelitis react intracellular neuronal antigens antibodies characteristically found patients underlying malignancy neurological impairment result neuronal death within last years major advances made understanding pathogenesis neurological disorders associated antibodies neuronal cell surface antigens contrast events lead neuronal death conditions associated antibodies directed intracellular antigens antiyo antihu remain poorly understood respective roles antibodies t lymphocytes causing neuronal injury defined animal model review discuss current knowledge two groups antibodies terms discovery arise interaction types antibodies molecular targets attempts made reproduce human neuronal injury tissue culture models experimental animals discuss emerging area autoimmune neuronal injury associated immune checkpoint inhibitors implications current research treatment affected patientspmid35111121 pmcpmc8801577 doi103389 fneur2021744653,0.0
perivascular space associated brain atrophy patients multiple sclerosis quant imaging med surg 2022 feb 12 2 10041019 doi 1021037 qims21705abstractbackground perivascular space pvs associated neurodegenerative neuroimmune diseases multiple sclerosis ms traditionally neuroimmune disease however studies show neurodegeneration also plays vital role ms present studies conclude severer pvs ms imaging marker neuroinflammation 7t mri study suggests pvs ms associated neurodegenerationmethods study 82 ms patients n82 32 healthy controls n32 enrolled following indexes measured number size distribution pvs pvs score corpus callosum index cci corpus callosum area cca ratio corpus callosum cranium ccr aligned third ventricle width a3vw unaligned third ventricle width u3vw results pvs score 4 vs 3 p0041 pvss number 10328045107 vs 8762530139 p0035 enlarged perivascular spaces epvss number 9 vs 1 p0001 ms patients significantly higher healthy controls pvss number 235 vs 13 epvss number 1 vs 0 basal ganglia bg epvss number 3 vs 0 centrum semiovale cso ms patients significantly higher healthy controls p0001 ms patients pvs correlated age hypertension extended disability status scale edss score clinical data ms patients pvs score correlated cca rs0272 p0013 ccr rs0219 p0048 pvss number correlated cca rs0255 p0021 correlation disappeared adjusting hypertension age ms patients remission pvss number correlated cca rs0487 p0019 ccr rs0479 p0021 pvs score correlated cca rs0453 p003 adjustment hypertension age total number pvss correlated cca rs0419 p0049 conclusions pvs load ms patients heavier healthy people especially bg cso pvs correlated edss ms patients pvs ms patients associated cca ccr pvss number independently related cca ms patients remissionpmid35111601 pmcpmc8739126 doi1021037 qims21705,0.0
estimating risk multiple sclerosis disease reactivation pregnancy postpartum viprims score front neurol 2022 jan 17 12766956 doi 103389 fneur2021766956 ecollection 2021abstractbackground evidence guiding personalized decisionmaking respect diseasemodifying therapy dmt around pregnancy relapsing multiple sclerosis rms lackingobjective generate validate risk score disease reactivation intrapartum postpartum rmsmethods vienna innsbruck ms database vimsd included 343 pregnancies patients rms primary endpoint disease reactivation patients randomly assigned 21 generation validation dataset predictive score calculated using cox regression validatedresults generation dataset occurrence relapse type dmt year conception dmt washout duration expanded disability status scale edss conception time dmt restart postpartum identified independent predictors disease reactivation p 0001 resulting 10point risk score robustly predicted reactivation explaining 75 variance p 0001 identifying patients high 6 points mean risk 65 range 50100 hazard ratio hr 145 intermediate 35 points mean risk 24 range 1535 hr 43 low risk 2 points mean risk 6 range 08 disease reactivation pregnancy 6 months postpartumconclusion composite vienna innsbruck pregnancy risk multiple sclerosis viprims score valuable clinical tool support patients neurologists anticipating risk thus individualizing treatment decisionmaking around pregnancypmid35111123 pmcpmc8801570 doi103389 fneur2021766956,0.0
role antifibrotic therapies treatment systemic sclerosisassociated interstitial lung disease ther adv musculoskelet dis 2022 jan 29 141759720x211066686 doi 101177 1759720x211066686 ecollection 2022abstractsystemic sclerosis ssc rare autoimmune condition complex pathogenesis characterized heterogeneous presentation different disease courses fibrosis multiple organs including lungs favored inflammation vasculopathy hallmark ssc sscassociated interstitial lung disease sscild common can associated poor outcomes complication leading cause death recent series huge heterogeneity sscild management can challenging immunosuppressive therapy long used prevent sscild progression modest effects clinical trials however thanks better understating ssc pathogenesis innovative therapies including antifibrotics increasingly developed achievement safety efficacy nintedanib systemic sclerosis senscis trial led approval drug agencies first antifibrotic drug sscild parallel antifibrotics investigated possible beneficial therapies sscild important unmet need remains clarify positioning various strategies added value combination immunosuppressants antifibrotic therapies patients high risk progression indeed irreversible lung injury selfperpetuated progression highlights concept window opportunity sscild patients herewith provide overview significant clinical trials antifibrotic drugs developed recent years management sscild viewpoint positioning treatment algorithmspmid35111241 pmcpmc8801639 doi101177 1759720x211066686,0.0
mimicking amyotrophic lateral sclerosis case spinal dural arteriovenous fistula case rep neurol 2021 dec 27 13 3 802806 doi 101159 000521030 ecollection 2021 sepdecabstracta number conditions can mimic amyotrophic lateral sclerosis als general excluded neurophysiological neuroimaging investigation present novel mimicking disorder 58yearold male without relevant past medical history presented 7year history progressive paraparesis examination bilateral thigh atrophy fasciculations asymmetric paraparesis severe left side upper motor neuron signs present lower limbs normal sensory examination needle emg disclosed mild chronic neurogenic changes lower limbs brain spinal cord neuroimaging normal namely dorsolumbar segment lumbar puncture showed mild hyperproteinorachia diagnosis slowly progressive possible als established one year later required bilateral support walk neurological examination revealed weak tendon reflexes abnormal pinprick proprioceptive sensation legs repeated lumbar mri showed extensive spinal cord oedema t7 conus multiple perimedullary vessel flow voids suggestive vascular malformation conventional angiography revealed spinal dural arteriovenous fistula l2l3 left l4 lumbar branch afferent artery dural arteriovenous fistula common vascular malformation spinal cord despite rare leads arterialization spinal veins causing venous hypertension spinal cord oedema ischaemia clinical picture includes stepwise sometimes fluctuant myeloradiculopathy case emg changes meet awaji criteria case reinforces need critically follow atypical cases ascertain clinical progression patients suspected alspmid35111029 pmcpmc8787513 doi101159 000521030,0.0
family planning people multiple sclerosis plain language summary neurodegener dis manag 2022 feb 3 doi 102217 nmt20210045 online ahead printabstractthis plain language summary article originally published journal frontiers neurology people multiple sclerosis often shortened ms may concerns pregnancy fertility understand concerns 332 people ms usa uk france germany italy spain took survey questions made family planning decisionsmost survey participants around 82 women survey found people ms less likely children people without ms half 56 people ms said disease impacted family planning decisions way almost one quarter 22 significantly changed plans timing pregnancy number children 14 decided children almost 4 5 81 people ms main source family planning information healthcare professionalsoverall ms significantly impacted patients decisions family planningpmid35112573 doi102217 nmt20210045,0.0
acute cardiovascular conditions setting multiple sclerosis relapse practical implications kardiol pol 2022 feb 3 doi 1033963 kpa20220025 online ahead printno abstractpmid35114003 doi1033963 kpa20220025,0.0
antiaquaporin4 immunoglobulin g colorimetric detection silver nanoparticles nanomedicine 2022 jan 31102531 doi 101016 jnano2022102531 online ahead printabstractneuromyelitis optica spectrum disorders nmosd inflammatory autoimmune disease whose biomarker antiaqp4igg autoantibody binds aquaporin4 aqp4 protein introduced nanosensor sensitivity 846 higher cbas 765 using silver nanoparticles agnps detected seropositive also falsenegative patients previously classified cba consisted agnps coated one panel 5 aqp4 epitopes ability detecting antiaqp4igg nmosd patients depended epitope synergy obtained combining different epitopes demonstrated nmosd patients easily distinguished healthy subjects patients multiple sclerosis using sensitive aqp46170 peptide established calibration curve estimate concentration antiaqp4igg seropositive nmosd patients ability enhance accuracy diagnosis may improve prognosis 1027 antiaqp4igg seronegative patients worldwidepmid35114406 doi101016 jnano2022102531,0.0
ebv linked multiple sclerosis nat rev microbiol 2022 feb 2 doi 101038 s41579022007014 online ahead printno abstractpmid35110729 doi101038 s41579022007014,0.0
peripheral helper t cells pathogenesis multiple sclerosis mult scler 2022 feb 313524585211067696 doi 101177 13524585211067696 online ahead printabstractbackground peripheral helper t cells tph likely implicated pathogenesis various inflammatory diseases tph cells share functions follicular helper t cells including plasma cell differentiation antibody productionobjective methods investigate possible role tph cells pathogenesis multiple sclerosis ms used flow cytometry analyze function phenotype central nervous system cns recruitment tph cells blood cerebrospinal fluid csf controls patients relapsingremitting rr primary progressive pp msresult study identified two functionally distinct tph cell populations regulatory counterpart tpr cells differences blood frequencies cytokine production potential interact b cells found controls patients ms along equal cnsmigration potential found tph cell populations enriched csf surprisingly increased frequency intrathecal tph cells control group compared patients msconclusion altogether find increased frequency csf tph cells patients rrms ppms findings indicate rather involved ms pathogenesis tph cells may implicated normal cns immunosurveillancepmid35112578 doi101177 13524585211067696,0.0
aerobic exercise effect pain sensitisation individuals musculoskeletal pain systematic review background pain sensitisation plays major role musculoskeletal pain however effective treatments limited although growing evidence exercise may improve pain sensitisation amount type exercise remains unclear systematic review examines evidence effect aerobic exercise pain sensitisation musculoskeletal conditionsmethodssystematic searches six electronic databases conducted studies included examined relationship aerobic physical activity pain sensitisation individuals chronic musculoskeletal pain excluding specific patient subgroups fibromyalgia risk bias assessed using cochrane methods qualitative analysis conductedresultseleven studies seven repeated measures studies four clinical trials 590 participants included eight studies low moderate risk bias 11 studies found aerobic exercise increased pressure pain thresholds decreased pain ratings musculoskeletal pain median minimum maximum improvement pain sensitisation 106 22 241 studies aerobic exercise involved walking cycling performed submaximal intensity incremental increases 460 min duration improvement pain sensitisation occurred one session observational studies 212 weeks clinical trialsconclusionsthese findings provide evidence aerobic exercise reduces pain sensitisation individuals musculoskeletal pain work needed determine whether translates improved patient outcomes including reduced disability greater quality life,0.0
atypical skeletal involvement patients erdheimchester disease ct imaging findings abstractobjectivesto review retrospectively atypical bone findings computed tomographic ct imaging patients erdheimchester diseasemethodsall 28 patients erdheimchester disease 13 men 15 women mean age 45 years range 763 years underwent chestabdomenpelvis ct ct images reviewed analyzed various features atypical bone lesions two radiologists consensusresultstwentyone patients atypical bone involvement radiologically atypical osseous lesions categorized three types diffuse nodular patchy eleven 52 21 patients spinal lesions four 36 diffuse type eight 73 nodular pattern six 55 patchy pattern sixteen 76 21 patients pelvic involvement two 13 diffuse nine 56 nodular 11 69 patchy ribs involved seven 33 21 patients nodular pattern one 14 patient patchy type six 86 patients clavicle involvement seen nine 43 21 patients diffuse type found one 11 patient nodular type six 67 patients solitary patchy type four 44 patients sternum involvement seen 10 48 21 patients nodularconclusionsthis series provides detailed description atypical bone involvement erdheimchester disease ct displays three major patterns understanding patterns may help increase accuracy diagnosis disease,0.0
rapidly progressive osteoarthritis hip establishing validating diagnostic criteria southeast asian population background study aimed establish quantitative diagnostic criteria rapidly progressive osteoarthritis rpoa hip compare criteria pathological hip entities asian populationmethodsfrom july 2011 september 2019 126 patients undergone hip replacement retrospectively recruited fasttrack joint replacement list patient demographics radiological parameters evaluated diagnosis hip rpoa established based lequesne et als criteria patients rpoa hip dysplasia avascular necrosis primary osteoarthritis allocated corresponding groups separately compared diagnostic criteria rpoa established validated sample populationresultsdiagnosis hip rpoa confirmed 18 patients mean age surgery 72 years significantly higher group dysplasia avascular necrosis groups mean pelvic tilt parameter 0485 rpoa group significantly lower groups mean initial tonnis angle 835 rpoa group significantly higher avascular necrosis osteoarthritis groups differences statistically significant rpoa nonrpoa groups limb shortening rate superior joint space narrowing acetabular destruction head destruction p 005 tonnis angle lateral subluxation also increased significantly disease progressionconclusionposterior pelvic tilt increased tonnis angle may contribute pathogenesis rpoa leading progressive acquired acetabular obliquity lateral subluxation propose modern comprehensive diagnostic criteria based existing literature current findings external validation recommended,0.0
neuronal grk2 regulates microglial activation contributes electroacupuncture analgesia inflammatory pain mice background g protein coupled receptor kinase 2 grk2 demonstrated play crucial role development chronic pain acupuncture alternative therapy widely used pain management study investigated role spinal neuronal grk2 electroacupuncture ea analgesiamethodsthe mice model inflammatory pain built subcutaneous injection complete freunds adjuvant cfa plantar surface hind paws mechanical allodynia mice examined von frey test mice subjected ea treatment bl60 st36 acupuncture points 1 week overexpression downregulation spinal neuronal grk2 achieved intraspinal injection adeno associated virus aav containing neuronspecific promoters microglial activation neuroinflammation evaluated realtime pcrresultsintraplantar injection cfa mice induced decrease grk2 microglial activation along neuroinflammation spinal cord ea treatment increased spinal grk2 reduced neuroinflammation significantly decreased cfainduced mechanical allodynia effects ea markedly weakened noncellspecific downregulation spinal grk2 intraspinal injection aav containing neuronspecific promoters specifically downregulated neuronal grk2 weakened regulatory effect ea cfainduced mechanical allodynia microglial activation meanwhile overexpression spinal neuronal grk2 decreased mechanical allodynia indicated neuronal grk2 mediated microglial activation neuroinflammation subsequently contributed cfainduced inflammatory painconclusionthe restoration spinal grk2 subsequent suppression microglial activation neuroinflammation might important mechanism ea analgesia findings suggested spinal grk2 especially neuronal grk2 might potential target ea analgesia pain management provided new experimental basis ea treatment pain,0.0
effect novel anticonvulsant chemical q808 gut microbiota hippocampus neurotransmitters pentylenetetrazoleinduced seizures rats background gut microbiota can modulate brain function behavior increasingly recognized important factor mediating risk epilepsy effects seizure interventions drug therapy one factors influence composition intestinal microbiota q808 innovative chemical strong anticonvulsant activity low neurotoxicity however studies evaluating effect q808 gut microbial communities lacking study aimed evaluate anticonvulsant activity q808 pentylenetetrazol ptz induced seizure model analyze compare intestinal microbiota composition nonptz vehicle control group ptzinduced seizure model rats without q808 16s rdna sequencing neurotransmitter levels hippocampus quantitatively estimated using hplcmsresultsthe results suggest q808 effectively alleviates seizures chronic ptzkindled model rats additionally based analyzed abundance gut microbiota dysbacteriosis model rats found corrected q808 treatment phylum level unique bacterial taxa eg lactobacillus associated acetylcholine production significantly increased several shortchain fatty acids scfas producing bacteria including roseburia alloprevptella prevotellaceae_nk3b31_group prevotellaceae_ucg001 prevotella_9 enriched hippocampus contents acetylcholine increased whereas levels 3methoxytyramine glutamine 5hydroxyindole acetic acid 5hiaa decreased q808 treatmentconclusionsthis study demonstrates q808 can used remodel dysbiosis gut microbiome influence neurotransmitter levels hippocampus ptzinduced seizure model rats hope novel findings prompt research interaction gut microbiota seizures mechanism q808,0.0
deep learning prediction population health costs background accurate prediction healthcare costs important optimally managing health costs however methods leveraging medical richness data health insurance claims electronic health records missingmethodshere developed deep neural network predict future cost health insurance claims records applied deep network ridge regression model sample 14 million german insurants predict total oneyear health care costs methods compared existing models various performance measures also used predict patients change costs identify relevant codes predictionresultswe showed neural network outperformed ridge regression well considered models cost prediction neural network superior ridge regression predicting patients cost change identified specific codesconclusionin summary showed deep neural network can leverage full complexity patient records outperforms standard approaches suggest better performance due ability incorporate complex interactions model model might also used predicting health phenotypes,0.0
involvement denervated midbrainderived factors formation ectopic corticomesencephalic projection hemispherectomy neuronal remodeling brain injury essential functional recovery unilateral cortical lesion axons intact cortex ectopically project denervated midbrain molecular mechanisms remain largely unknown address issue examined gene expression profiles denervated intact mouse midbrains hemispherectomy early developmental stages using mice either sex ectopic contralateral projection occurs robustly analysis showed various axon growthrelated genes upregulated denervated midbrain genes reportedly expressed glial cells identify underlying molecules receptors candidate upregulated molecules knocked layer 5 projection neurons intact cortex using crispr cas9mediated method axonal projection knockedout cortical neurons examined hemispherectomy found ectopic projection significantly reduced integrin subunit three neurotrophic receptor tyrosine kinase 2 also known trkb knocked overall present study suggests denervated midbrainderived glial factors contribute lesioninduced remodeling corticomesencephalic projection via receptorssignificance statement brain injury compensatory neural circuits established contribute functional recovery however little known intrinsic mechanism underlies injuryinduced remodeling found unilateral cortical ablation expression axongrowth promoting factors elevated denervated midbrain involved formation ectopic axonal projection intact cortex evidence demonstrated factors expressed astrocytes microglia activated denervated midbrain thus present study provides new insight mechanism lesioninduced axonal remodeling therapeutic strategies brain injury,0.0
ofatumumab relapsing forms multiple sclerosis drugs today barc 2022 jan 58 1 921 doi 101358 dot20225813353168abstractin recent years b cells extensively studied therapeutic target multiple sclerosis ms particularly anticd20 monoclonal antibodies mabs rituximab ocrelizumab proven effective treating various forms ms ofatumumab secondgeneration anticd20 igg1 fully human mab binds different membraneproximal epitope cd20 compared anticd20 mabs thus ensuring slower dissociation rate results dosedependent bcell depletion mainly exerted mechanism complementdependent cytotoxicity repletion kinetic faster rituximab ocrelizumab ofatumumab first approved drug relapsing forms ms administered via subcutaneous injection every 4 weeks two phase ii two phase iii clinical trials shown effective reducing annualized relapse rate clinical disability worsening well suppressing magnetic resonance imaging mri disease activity safety profile drug proven favorable good tolerability low immunogenic risk moreover subcutaneous injection grants easier way administration current evidence ofatumumab efficacy safety reviewed present articlepmid35107090 doi101358 dot20225813353168,0.0
multisystem screening reveals sarscov2 neurons myenteric plexus megakaryocytes j pathol 2022 feb 2 doi 101002 path5878 online ahead printabstractsarscov2 causative agent covid19 typically manifests respiratory illness although extrapulmonary involvement gastrointestinal tract nervous system well frequent thrombotic events increasingly recognised maps onto sarscov2 organ tropism histological level however remains unclear perform comprehensive validation monoclonal antibody sarscov2 nucleocapsid protein np followed systematic multisystem organ immunohistochemistry analysis viral cellular tropism tissue 36 patients 16 postmortem cases 16 biopsies polymerase chain reaction pcr confirmed sarscov2 status peaks pandemic 2020 four precovid postmortem controls sarscov2 antinp staining postmortem cases revealed broad multiorgan involvement respiratory digestive haematopoietic genitourinary nervous systems typical pattern staining characterised punctate paranuclear apical cytoplasmic labelling average time symptom onset time death shorter positively versus negatively stained postmortem cases mean 103 days versus mean 203 days p 00416 cases showing definitive staining interval exceeded 15 days one striking finding widespread presence sarscov2 np neurons myenteric plexus site high ace2 expression entry receptor sarscov2 one earliest affected cells parkinsons disease bone marrow observed viral sarscov2 np within megakaryocytes key cells platelet production thrombus formation 15 tracheal biopsies performed patients requiring ventilation near complete concordance immunohistochemistry pcr swab results going forward findings relevance correlating clinical symptoms organ tropism sarscov2 contemporary cases well providing insights potential longterm complications covid19 article protected copyright rights reservedpmid35107828 doi101002 path5878,0.0
covid19 hospitalizations intensive care unit stays ventilation death among patients immune mediated inflammatory diseases compared controls j rheumatol 2022 feb 1jrheum211012 doi 103899 jrheum211012 online ahead printabstractobjective investigate covid19 hospitalization risk patients immune mediated inflammatory diseases imids compared matched nonimid comparators general populationmethods conducted populationbased matched cohort study using health administrative data january july 2020 ontario canada cohorts following imids assembled rheumatoid arthritis ra psoriasis psoriatic arthritis psa ankylosing spondylitis systemic autoimmune rheumatic diseases sards multiple sclerosis ms iritis inflammatory bowel disease polymyalgia rheumatica vasculitis patient matched 5 nonimid comparators based sociodemographic factors compared cumulative incidence hospitalizations covid19 outcomes imid nonimid patientsresults total 493 499 imid patients 417 hospitalizations 2 466 946 nonimid comparators 1 519 hospitalizations assessed odds hospitalized covid 19 significantly higher patients imids compared matched nonimid comparators matched unadjusted odds ratio 137 adjusted 123 significantly higher risk hospitalizations found patients iritis 146 ms 183 psa 220 ra 142 sards 147 vasculitis 207 covid19 hospitalizations associated older age male sex longterm care residence multimorbidity lower income odds complicated hospitalizations 21 higher among imid versus matched nonimid patients association attenuated adjusting demographic factors comorbiditiesconclusion patients imids higher risk hospitalized covid19 risk explained part comorbiditiespmid35105713 doi103899 jrheum211012,0.0
humoral cellular responses sarscov2 convalescent covid19 patients multiple sclerosis neurol neuroimmunol neuroinflamm 2022 feb 1 9 2 e1143 doi 101212 nxi0000000000001143 print 2022 marabstractbackground objectives information humoral cellular responses severe acute respiratory syndrome coronavirus 2 sarscov2 antibody persistence convalescent covid19 patients multiple sclerosis pwms scarce objectives study investigate factors influencing humoral cellular responses sarscov2 persistence convalescent covid19 pwmsmethods retrospective study confirmed covid19 convalescent pwms identified february 2020 may 2021 sarscov2 antibody testing examined relationships demographics ms characteristics diseasemodifying therapy dmt humoral immunoglobulin g spike nucleocapsid proteins cellular interferongamma ifn responses sarscov2results total 121 8345 145 pwms seropositive 25 42 595 presented cellular response 131 months covid19 anticd20treated patients lower antibody titers dmts p 0001 severe covid19 longer time last infusion increased likelihood producing humoral response ifn levels differ among dmt five 7 714 anticd20treated seronegative patients cellular response humoral response persisted 6 months 41 56 8113 pwms multivariate analysis seropositivity decreased due anticd20 therapy 008 95 ci 001055 increased males 359 1021268 whereas cellular response decreased progressive disease 004 0001088 factors associated antibody persistencediscussion humoral cellular responses sarscov2 present covid19 convalescent pwms 1310 months covid19 humoral response decreases anticd20 treatment although cellular response can detected anticd20treated patients even absence antibodiespmid35105687 doi101212 nxi0000000000001143,0.0
dimethyl fumarate decreases shortterm longterm inflammation focal eae model neuroinflammation ejnmmi res 2022 feb 2 12 1 6 doi 101186 s1355002200878yabstractbackground dimethyl fumarate dmf oral immunomodulatory drug used treatment autoimmune diseases sought study whether effect dmf can detected using positron emission tomography pet targeting 18kda translocator protein tspo focal delayedtype hypersensitivity rat model multiple sclerosis fdtheae rats treated orally twice daily lesion activation day 0 either vehicle tap water 008 methocel 200 l control group n 4 3 week four 15 mg kg dmf n 4 008 aqueous methocel 200 l 8 weeks animals imaged pet using tspo tracer 18f ge180 weeks 0 1 2 4 8 18 following lesion activation nondisplaceable binding potential bpnd calculated immunohistochemical staining iba1 cd4 cd8 performed week 18 separate cohorts animals following 2 4 weeks treatmentresults using fdtheae model dmf reduced 18f ge180 bpnd dmftreated animals compared control animals 1 week treatment twotailed unpaired t test p 0031 weeks 2 4 8 18 imaged vivo pet immunostaining iba1 showed dmf effect perilesional volume core lesion volume 2 4 weeks treatment 18 weeks however optical density od measurements cd4+ staining showed reduced od lesions treated ratsconclusions dmf reduced microglial activation fdtheae model 1 week treatment detected pet imaging tspo ligand 18f ge180 however extended time course reduced microglial activation observed using 18f ge180 immunohistochemistry iba1+ microglia macrophages additionally dmf affect infiltration cd4+ cd8+ tlymphocytes fdtheae lesionpmid35107664 doi101186 s1355002200878y,0.0
ofatumumab subcutaneous injection treatment relapsing forms multiple sclerosis expert rev clin immunol 2022 feb 2 doi 101080 1744666x20222031982 online ahead printabstractintroduction recent years different studies highlighted importance b cells pathophysiology multiple sclerosis ms secrete cytokines modulate inflammatory environment present antigens activation t lymphocytes secrete antibodies contributing destruction myelin sheath combined findings lead new possible means treating msareas covered review provide uptodate overview characteristics ofatumumab aka kesimpta differences drug anticd20 monoclonal antibodies used treat msexpert opinion evolution diseasemodifying treatment algorithms ms underlines importance starting treatment soon diagnosis defined adequate treatment intensity monoclonal antibodies aggressive treatments now considered option clinical presentation disease based prognostic profile emerging clinical paraclinical investigations recent adoption new diagnostic criteria allows early diagnosis ms together availability diseasemodifying therapies dmts ofatumumab good efficacy safety profile easy administer contribute significant improvements longterm prognosis mspmid35107057 doi101080 1744666x20222031982,1.0
significant association rs77493513 polymorphism 3#39 utr nrg1 gene risk multiple sclerosis disease metab brain dis 2022 feb 2 doi 101007 s11011022009229 online ahead printabstractmultiple sclerosis ms chronic inflammatory autoimmune disease characterized demyelination central nervous system cns neuregulin 1 nrg1 signaling protein plays important role variety biological processes including potentiate oligodendrocyte differentiation myelination cns immune response regulation inflammation single nucleotide polymorphism snp rs77493513 located untranslated region 3 mrna 3utr nrg1 gene predicted binding site several micrornas may play important role posttranscriptional regulation study aimed investigate association snp rs77493513 nrg1 gene risk ms disease study genomic dna extracted whole blood samples 182 patients relapsingremitting multiple sclerosis rrms 198 controls different genotypes rs77493513 polymorphism determined using rflppcr technique statistical analysis performed using spss 210 software t 2 logistic regression tests data showed genotypes ac or363 ci 193681 p0001 cc or790 ci 4131511 p0001 significantly increased risk ms disease c allele risk allele also ac or016 ci 004063 p 0009 cc or014 ci 003053 p004 genotypes significantly decrease age onset disease results show allele c rs77493513 polymorphism nrg1 gene can risk factor mspmid35106689 doi101007 s11011022009229,1.0
healthrelated quality life people multiple sclerosis population compare populationbased norms different health domains j patient rep outcomes 2022 feb 2 6 1 12 doi 101186 s41687022004154abstractpurpose purposes investigation 1 identify domains healthrelated quality life impacted people rrms 2 compare healthrelated qol people rrms general population norms 3 describe subgroups within rrms population similar health wellness needsmethods crosssectional qol investigation adults rrms sf36v2 survey demographic information collected electronically via qualtrics participants n 120 recruited social media national multiple sclerosis society united states onesample ztests completed subscales component mean scores determine difference sample population norms existedresults values z statistically significant p 01 subscale composite scores social function physical function mental health component scores lowest subscale means first stage depression screen revealed 49 surveyed population risk depression compared 18 general population dividing sample years since ms diagnosis recently diagnosed group 61 risk depressionconclusions challenges related mental health individuals rrms influencing overall healthrelated qol early disease course 03 years mental health affected qol physical health attention must given nonphysical domains health advance qol people rrmspmid35107657 doi101186 s41687022004154,0.0
vitamin d ophthalmopathias review cesk slov oftalmol 2022 winter 2 ahead print 10011004abstractthe importance vitamin d3 hydroxycholecalciferol one liposoluble vitamins known prevention treatment metabolic bone diseases rickets osteomalacia osteoporosis recent years however information increased importance vitamin d3 numerous organ systems pathogenesis various diseases e g ophthalmopathies immunological functions vitamin d3 subject studies dealing autoimmune optic nerve disorders results appear positive effect demyelinating diseases also plays important role maintaining thickness retinal nerve fiber layer additional administration successful optical neuritis may first sign multiple sclerosis appears sufficient serum vitamin d3 levels may protect patients deterioration form attack demyelination course diabetic retinopathy probably also influenced vitamin d3 inter alia correlating fact receptor enzymes metabolism expressed retina low serum levels vitamin d3 may even trigger agerelated macular degeneration conversely higher dietary intake vitamin d3 may positively affect neovascularization optimal level hydroxycholecalciferol 60 200 nmol l severe deficit represents decrease 25 nmol l body can normally produce 10 000 iu vitamin exposure sunlight however demonstration protective character connection mentioned diseases retina optic nerve will require sufficient number studies confirm facts found far rediscovered vitaminpmid35105147,1.0
slowly expanding lesions predict 9year multiple sclerosis disease progression neurol neuroimmunol neuroinflamm 2022 feb 1 9 2 e1139 doi 101212 nxi0000000000001139 print 2022 marabstractbackground objectives chronic active lesions contribute multiple sclerosis ms severity association longterm disease progression evaluated yet white matter wm lesions showing linear expansion time serial t1 t2weighted scans ie slowly expanding lesions sels proposed marker chronic inflammation study assessed whether sel burden microstructural abnormalities associated expanded disability status scale edss score worsening secondary progressive sp conversion 91year followup patients relapsingremitting rr msmethods 52 patients rrms sels identified among wm lesions linearly fitting jacobian nonlinear deformation field time points obtained combining 3t brain t1 t2weighted scans acquired baseline months 6 12 24 logistic regression analysis applied investigate associations sel number volume magnetization transfer ratio mtr t1weighted signal intensity disability worsening ie edss score increase sp conversion median followup 91 yearsresults followup 20 52 38 patients ms showed edss score worsening 13 52 25 showed sp conversion higher baseline edss score point higher 315 95 ci 161 838 p 0003 higher proportion sels among baseline lesions increase 122 104 158 p 004 lower baseline mtr values sels higher 066 041 092 p 0033 significant independent predictors edss score worsening followup cindex 0892 higher baseline edss score point higher 637 198 2053 p 0002 lower baseline mtr values sels higher 048 025 089 p 002 independently predicted spms conversion cindex 0947 discussion proportion sels associated ms progression 9 years severe sel microstructural abnormalities independently predict edss score worsening spms conversion quantification sel burden damage using t1 t2weighted mtr sequences may identify patients rrms higher risk longterm disability progression spms conversionclassification evidence study provides class iii evidence patients rrms starting treatment natalizumab fingolimod proportion sels brain mri associated edss score worsening spms conversion 9year followuppmid35105685 doi101212 nxi0000000000001139,0.0
effectiveness rituximab vs ocrelizumab treatment primary progressive multiple sclerosis realworld observational study j neurol 2022 feb 2 doi 101007 s00415022109890 online ahead printabstractintroduction ocrelizumab anticd20 antibody drug approved treat patients primary progressive multiple sclerosis pwppms candidates receive treatment due prescription limitations rituximab another anticd20 antibody used offlabel pwppms ocrelizumab approval however studies comparing effectiveness drugs lackingobjective evaluate effectiveness rituximab ocrelizumab pwppms reallife conditionsmethods conducted multicentric observational study pwppms started ocrelizumab rituximab according clinical practice minimum followup 1 year data collected prospectively retrospectively primary outcome time confirmed disability progression 3 months cdw secondary outcome serum neurofilament light chain levels snfl end followupresults 95 111 pwppms fulfilled inclusion criteria followup data availability 49 516 received rituximab 46 484 ocrelizumab rituximabtreated patients significantly higher baseline edss disease duration history previous diseasemodifying treatment dmt ocrelizumabtreated patients mean followup 183 months sd 59 26 patients experienced cdw 214 15 306 rituximab group 11 239 ocrelizumab group survival analysis revealed differences time cdw snfl measured 60 patients differences groups foundinterpretation provide realworld evidence effectiveness ocrelizumab rituximab pwppms differences time cdw found treatments however study establish equivalence treatments warrant clinical trial confirm findingspmid35107597 doi101007 s00415022109890,0.0
roles mir155 neuroinflammation neurological disorders potent biological therapeutic target cell mol neurobiol 2022 feb 2 doi 101007 s1057102201200z online ahead printabstractneuroinflammation plays crucial role development progression neurological disorders microrna155 mir155 mir known play inflammatory responses associated susceptibility inflammatory neurological disorders neurodegeneration including alzheimers disease parkinsons disease multiple sclerosis amyotrophic lateral sclerosis well epilepsy stroke brain malignancies mir155 damages central nervous system cns enhancing expression proinflammatory cytokines like il1 il6 tnf irf3 also disturbs bloodbrain barrier decreasing junctional complex molecules claudin1 annexin2 syntenin1 dedicator cytokinesis 1 dock1 hallmark many neurological disorders review discusses molecular pathways involve mir155 critical component progression neurological disorders representing mir155 viable therapeutic targetpmid35107690 doi101007 s1057102201200z,0.0
new master#39 s program multiple sclerosis management wien med wochenschr 2022 feb 2 doi 101007 s10354021009003 online ahead printabstractthe new study program multiple sclerosis management aimed physicians therapists nurses scientists pharmacists psychologists biologists want specialize field multiple sclerosis ms successful accreditation 2019 first students masters program offered dresden international university diu since 2020 period four semesters can completed parttime largely digitally masters program divided six modules focusing basics clinical diagnostic aspects ms studies statistics diseasemodifying symptomatic therapy disease monitoring documentation teaching includes theoretical parts numerous practical units goal derive therapeutic intervention plans problemsolving strategies scientific publications clinical studies develop apply patient care lecturers come germany austria switzerland predominantly professors german multiple sclerosis society patron course article presents study program detailpmid35107651 doi101007 s10354021009003,0.0
roles microglia astrocytes phagocytosis myelination insights cuprizone model multiple sclerosis glia 2022 feb 2 doi 101002 glia24148 online ahead printabstractin human demyelinating diseases multiple sclerosis ms imbalance demyelination remyelination can trigger progressive degenerative processes clearance myelin debris phagocytosis site demyelination microglia critically important achieve adequate remyelination slow progression disease however microglia phagocytose myelin debris clearance impaired ms fully known likewise role microglia remyelination remains unclear recent studies using cuprizone cpz animal model central nervous system demyelination revealed upregulation signaling proteins microglia facilitates effective phagocytosis myelin debris moreover demyelination protective mediators released activated microglia resulting acceleration remyelination cpz model contrast inadequate microglial activation recruitment site demyelination production toxic mediators impairs remyelination resulting progressive demyelination addition microgliamediated phagocytosis astrocytes play important role phagocytic process recruiting microglia site demyelination producing regenerative mediators current review update emerging findings cpz animal model discussing roles microglia astrocytes phagocytosis myelinationpmid35107839 doi101002 glia24148,1.0
sustained immunotolerance multiple sclerosis stem cell transplant ann clin transl neurol 2022 feb 1 doi 101002 acn351510 online ahead printabstractobjective autologous haematopoietic stem cell transplantation ahsct potential induce sustained periods disease remission multiple sclerosis ms inflammatory disease central nervous system cns characterised demyelination axonal degeneration however mechanisms associated durable treatment responses ms require elucidationmethods characterise longer term immune reconstitution effects ahsct 24 36 months m posttransplant highdimensional immunophenotyping peripheral blood mononuclear cells 22 ms patients performed using two customdesigned 18colour flow cytometry panelsresults higher baseline frequencies specific proinflammatory immune cells thelper17 th17 cells mucosalassociated invariant tcells cnshoming tconventional tconv cells observed ms patients decreased postahsct 36m accompanied postahsct increase frequencies absolute counts immunoregulatory cd56hi natural killer cells 24m terminally differentiated cd8+ cd28 cd57+ cells 36m sustained increase proportion nave bcells persistent depletion memory bcells plasmablasts observed 36m reconstitution bcell repertoire accompanied reduction frequency circulating tfollicular helper cells ctfh expressing programmed cell death1 pd1+ 36m associations frequency dynamics clinical outcomes indicated responder patients exhibit decrease th17 cnshoming tconv pd1+ ctfh proinflammatory subsets 36m increase cd39+ tregulatory cells 24minterpretation ahsct induces substantial recalibration proinflammatory immunoregulatory components immune system ms patients 36m posttransplantpmid35106961 doi101002 acn351510,1.0
multimorbidity resilience covid19 pandemic selfreported impact worry among older adults study based canadian longitudinal study aging clsa background coronavirus disease2019 covid19 pandemic created spectrum adversities affected older adults disproportionately paper examines older adults multimorbidity using longitudinal data ascertain vulnerable individuals coped pandemicinduced risk stressors better others termed multimorbidity resilience investigate prepandemic levels functional social psychological forms resilience among subpopulation atrisk individuals two outcomes selfreported comprehensive pandemic impact personal worrymethodsthis study conducted using followup 1 data canadian longitudinal study aging clsa baseline exit covid19 study conducted april december 2020 final subgroup 9211 older adults two chronic health conditions selected analyses logistic regression generalized linear mixed models employed test hypotheses multimorbidity resilience index three subindices measured using prepandemic followup 1 data outcomes including covariatesresultsthe multimorbidity resilience index inversely associated pandemic comprehensive impact covid19 baseline wave 083 p 0001 95 ci 080 086 exit wave 084 p 0001 95 ci 081 087 personal worry exit 089 p 0001 95 ci 086 093 final models covariates full index also associated comprehensive impact covid waves estimate 019 p 0001 95 ci 022 016 psychological resilience subindex inversely associated comprehensive impact baseline 089 p 0001 95 ci 087 091 exit waves 089 p 0001 95 ci 087 091 final model covid waves estimate 011 p 0001 95 ci 013 010 social resilience subindex exhibited weak positive association 104 p 005 95 ci 101 107 personal worry functional resilience measure associated either outcomeconclusionsthe findings show psychological resilience pronounced protecting pandemic comprehensive impact personal worry addition several covariates also associated outcomes findings discussed terms developing retrofitting innovative approaches proactive coping among multimorbid older adults prepandemic peripandemic periods,0.0
elevated proportion tlr2 tlr4expressing th17like cells activated memory b cells associated clinical activity cerebral cavernous malformations background recent evidences suggested involvement tolllike receptor tlr 4 pathogenesis cerebral cavernous malformations ccm elevated frequency tlr+tcells associated neurological inflammatory disorders tcells bcells found ccm lesions objective present study evaluate cytokine profile tcells expressing tlr2 tlr4 well bcell subsets asymptomatic ccmasympt symptomatic ccmsympt patientsmethodsfor study cytokine profile tlr2+ tlr4+ tcell bcell subsets ccmasympt ccmsympt patients investigated using flow cytometry elisa tcells stimulated vitro anticd3 anticd28 beads tlr2 pam3c tlr4 lps ligandsresultsccmsymptc patients presented higher frequency tlr4+ cd4+ cd8+ tcells greater density tlr4 expression cells regard cytokine profile percentage tlr2+ tlr4+ th17 cells higher ccmsympt patients addition elevated proportion tlr4+ tc1 cells well tc17 th171 cells expressing tlr2 tlr4 observed symptomatic patients contrast percentage tlr4+ il10+cd4+ t cells higher ccmasympt group pam3c lps able elevate frequency il6+cd4+t cells th171 cells ccmsympt cell cultures furthermore comparison asymptomatic patients purified tcells ccmsympt group released higher levels th17related cytokines response pam3c mainly lps well activation via tcr cd28 concerning bcell subsets higher frequency memory memory activated bcells observed ccmsympt patientsconclusionsour findings reveal increase circulating th17 tc17 cell subsets expressing functional tlr2 mainly tlr4 molecules associated increase memory bcell subsets ccm patients clinical activity disease,0.0
administration maresin1 ameliorates physiopathology experimental autoimmune encephalomyelitis background resolution inflammation active regulated process leads clearance cell debris immune cells challenged tissue facilitating recovery homeostasis physiological response coordinated endogenous bioactive lipids known specialized proresolving mediators spms resolution fails inflammation becomes uncontrolled leading chronic inflammation tissue damage occurs multiple sclerosis ms methodsspms key biosynthetic enzymes involved spm production analysed metabololipidomics qpcr active brain lesions serum peripheral blood mononuclear cells pbmc ms patients well spinal cord mice experimental autoimmune encephalomyelitis eae also tested therapeutic actions spm coined maresin1 mar1 eae mice studied impact inflammation luminex flow cytometry analysisresultswe show levels mar1 spms limit detection increased spinal cord eae mice whereas production proinflammatory eicosanoids induced disease progression similarly reveal spms undetected serum active brain lesion samples ms patients linked impaired expression enzymes involved biosynthetic pathways spms demonstrate exogenous administration mar1 eae mice suppressed protein levels various proinflammatory cytokines reduced immune cells counts spinal cord blood mar1 also decreased numbers th1 cells increased accumulation regulatory t cells drove macrophage polarization towards antiinflammatory phenotype importantly provide clear evidence administration mar1 mice clinical signs eae enhanced neurological outcomes protected demyelinationconclusionsthis study reveals imbalance production spms ms patients eae mice increasing bioavailability spms mar1 minimizes inflammation mediates therapeutic actions thus data suggest immunoresolvent therapies mar1 novel avenue treatment ms,1.0
improvement gait balance patients multiple sclerosis multidisciplinary physical rehabilitation analysis realworld data russia multidisciplinary physical rehabilitation effective method impovement gait balance disturbances patients msamong various baseline characteristics disease duration edss score age patients significant predictors improvementrehabilitation outcomes measures based level disability patientsapplied mcids require standardization relieble evaluation rehabilitation methods,1.0
estimation medical cost multiple sclerosis iran 20192020 background due high increasing economic burden chronic diseases including multiple sclerosis ms aimed investigate medical cost ms iranmethodsthis descriptive crosssectional study conducted using comprehensive national prescription data irans health insurance organization ihio rehabilitation data ministry health iran welfare organization time period considered study 20192020 order calculate medical cost ms costofillness coi method used based prevalencebased approach cost medications determining diagnosing ms risk followup rehabilitation estimatedresultsthe total medical cost ms iran 20192020 estimated 238 124 160 medications rehabilitation services largest share medical cost ms iran 80 19 respectively cost share determining diagnosing disease risk accounted less 1 total medication cost estimated equal 192 298 thousand total cost determining diagnosing ms risk estimated 348 574 total cost rehabilitation services ms subgroups 20192020 estimated 45 477 205conclusionsresults calculating medical cost ms iran 20192020 showed significant burden iranian health care system society among medication cost largest share requires serious attention health system policymakers,0.0
mesenchymal stem cells combined autocrosslinked hyaluronic acid improve mouse ovarian function activating pi3kakt pathway paracrine manner background declining ovarian function advanceaged women premature ovarian insufficiency poi patients seriously affects quality life currently effective treatment rescue ovarian function clinic stem cell transplantation promising therapeutic strategy ovarian aging clinical application limited due low efficiency unclear mechanism novel combination umbilical cordmesenchymal stem cells ucmscs autocrosslinked hyaluronic acid ha gel explored rescue ovarian reserve fecundity poi naturally aging micemethodsto investigate ha prolonged survival ucmscs transplantation pcr immunofluorescence performed track cells day 1 3 7 14 transplantation effects ha ucmscs analyzed cck8 assay rnasequencing 440 cytokine array vivo experiments conducted evaluate therapeutic effects ucmscs combined ha transplantation 4vinylcyclohexene diepoxide vcd induced poi mice naturally aging mice model ovarian function analyzed ovarian morphology follicle counts estrous cycle hormone levels fertility ability investigate mechanisms stem cell therapy conditioned medium collected ucmscs fibroblast vitro ovarian culture model 440 cytokine array applied assess paracrine effect determine underlying mechanism hepatocyte growth factor hgf identified effective factor verified hgf cytokine neutralization antibody supplementation ovarian culture systemresultsha prolongs retention ucmscs ovary also boosts secretory function ucmscs promote follicular survival activating pi3kakt pathway paracrine mechanism vitro vivo importantly hgf identified key functional cytokine secreted mscsconclusionsthe results show ha excellent cell scaffold improve treatment efficiency ucmscs ovarian aging physiological pathological conditions therapeutic mechanism activation pi3kakt pathway via hgf findings will facilitate clinical application mscs transplantation ovarian disorders,0.0
vagus nerve stimulation modulates hippocampal inflammation caused continuous stress rats background previous studies shown vagus nerve stimulation vns can attenuate inflammatory responses peripheral tissues also improve neurological disorders cognitive function brain however clear vns involved neuropathological processes brain tissues investigated regulatory effects vns production proinflammatory cytokines hippocampus animal model continuous stress cs methodscs induced placing rats cages immersed water acute chronic electrical stimulation applied cervical vagus nerve cs animals protein levels gastric hippocampal tissues measured western blotting protein signals analyzed immunofluorescence staining von frey test forced swimming test performed assess pain sensitivity depressivelike behavior rats respectivelyresultslevels tnf il1 il6 gastric hippocampal tissues significantly increased cs animals compared untreated control downregulated acute vns avns iba1labeled microglial cells hippocampus cs animals revealed morphological features activated inflammatory cells changed normal shape vns vns elevated hippocampal expression 7 nicotinic acetylcholine receptors 7 nachr cs animals pharmacological blockade 7 nachr increased production tnf il1 il6 thus suppressing cholinergic antiinflammatory activity mediated vns chronic vns cvns downregulated hippocampal production active form caspase 3 5ht1a receptors also decreased levels tnf il1 il6 gastric hippocampal tissues cs animals pain sensitivity depressivelike behavior increased cs improved cvnsconclusionsour data suggest vns may involved modulating pathophysiological processes caused cs brain,0.0
roles eph receptors neuropilin1 p2x7 cd147 covid19associated neurodegenerative diseases inflammasome jak inhibitors potential promising therapies abstractthe novel coronavirus disease 2019 covid19 pandemic spread worldwide finding safe therapeutic strategy effective vaccine critical overcoming severe acute respiratory syndrome coronavirus 2 sarscov2 therefore elucidation pathogenesis mechanisms especially entry routes sarscov2 may help propose antiviral drugs novel vaccines several receptors demonstrated interaction spike s protein sarscov2 host cells including angiotensinconverting enzyme ace2 ephrin ligands eph receptors neuropilin 1 nrp1 p2x7 cd147 expression entry receptors central nervous system cns may make cns prone sarscov2 invasion leading neurodegenerative diseases present review provides potential pathological mechanisms sarscov2 infection cns including entry receptors cytokines involved neuroinflammatory conditions moreover explains several neurodegenerative disorders associated covid19 finally suggest inflammasome jak inhibitors potential therapeutic strategies neurodegenerative diseases,0.0
cocreating patients impact framework across medicines life cycle qualitative study exploring patients experiences involvement perceptions impact measures background biopharmaceutical industry challenged efficiently delivering medicines patients truly value can addressed engaging patients caregivers throughout medicines life cycle ensuring products meet needs expectations take isolated best practice examples patient engagement exist remain relatively ad hoc fully embedded within research development rd practices encourage patient engagement impact patient engagement projects pep must objectively measured demonstrated frameworks proposed however evidence widespread adoption patients perspectives robustly explored objective qualitative study therefore understand patients perspectives impact measurement can systematically applied within biopharmaceutical companymethodssemistructured interviews conducted 13 patient organisation po representatives exploring experiences engagement reflections 23 candidate patient engagement impact measures categorised five groups medicines rd priorities clinical trial design regulatory market access submissions product support information disease support information thematic analysis undertaken impact measures revised line interview participant feedback emerging themes revisions impact measures validated joint workshop 4 patient advisors representing 4 posresultsthe study revealed po representatives feel deep sense accomplishment ownership collaborating peps biopharmaceutical companies largely conceptualise impact positive tangible useful outcomes revisions made predefined patient engagement impact measures fell three broad categories 1 requirement greater context 2 capturing nature patient influence 3 terminology changes greatest number revisions concerned requiring greater context example including additional descriptions patient quotes satisfactionconclusionsthis study sheds light patient advocates view impact typically means delivering value important therefore authors paper created term valueimpact comprehensively characterise conceptualisation propose valueimpact measurement plan incorporating longitudinal data understanding light recently published work widescale adoption implementation measurement valueimpact across biopharmaceutical industry can realised,0.0
erp57#x2f pdia3 new insight abstractthe erp57 pdia3 protein pleiotropic member pdis family although predominantly located endoplasmic reticulum er indeed found cellular compartments nucleus cell membrane erp57 pdia3 important research target considering can found various subcellular locations protein involved many different physiological pathological processes review describes new data functions summarizes ligands identified pdia3specific inhibitors,0.0
association personality traits physical function cognition mood multiple sclerosis abstractbackgroundgrowing literature supports hypothesis personality influences health outcomes studies examined association personality traits key clinical manifestations persons multiple sclerosis pwms objectiveto investigate whether personality traits associated physical function cognition depression persons msmethodsin crosssectional study analyzed data two cohorts upmc n365 cuimc n129 participants completed personality scale assessing neuroticism extraversion openness agreeableness conscientiousness validated surveys measuring physical function cognition depression stepwise linear regressions used evaluate associations personality traits outcome measuresresultsconsistently across cohorts higher extraversion associated better physical function whereas higher neuroticism associated worse depression first cohort higher extraversion associated better cognition higher neuroticism associated greater risk memory impairment second cohort relationships independent age disease durationconclusionfindings suggest potentially protective role extraversion harmful role neuroticism msspecific patientreported clinical outcomes increased understanding interplay personality health outcomes may inform risk models physical decline cognitive impairment depression pwms,0.0
intersecting kinematic encoding readout intention autism proc natl acad sci u s 2022 feb 1 119 5 e2114648119 doi 101073 pnas2114648119abstractobservers autism spectrum disorders asds find difficult read intentions movements however computational bases difficulties unknown difficulties reflect intention readout deficit likely rooted kinematic dis similarities typical asd kinematics combined motion tracking psychophysics computational analyses uncover singletrial intention readout computations typically developing td children n 35 children asd n 35 observed actions performed td children children asd average intention discrimination performance chance td observers asd observers however singletrial analysis showed td asd observers read singletrial variations movement kinematics td readers better able identify intentioninformative kinematic features observation td actions conversely asd readers better able identify intentioninformative features observation asd actions crucially td observers generally able extract intention information encoded movement kinematics autism unable results extend existing conceptions mind reading asd suggesting intention reading difficulties reflect interaction failure rooted kinematic dissimilarity td asd kinematics level feature identification individual readout deficit level information extraction accompanied overall reduced sensitivity intention readout singletrial variations movement kinematicspmid35101921 doi101073 pnas2114648119,0.0
patients multiple sclerosis acquire disability brain 2022 feb 1awac016 doi 101093 brain awac016 online ahead printabstractpatients multiple sclerosis acquire disability either 1 relapseassociated worsening raw 2 progression independent relapse activity pira study addresses relative contribution relapses disability worsening course disease early progression begins extent multiple sclerosis therapies delay disability accumulation using novartisoxford ms noms data pool spanning multiple sclerosis phenotypes pediatric multiple sclerosis evaluated 200 000 edss transitions 27 000 patients 15 years followup analyzed three datasets full analysis dataset containing observational randomized controlled clinical trials disability relapses assessed n 27 328 b phase 3 clinical trials n 8364 c placebocontrolled phase 3 clinical trials n 4970 determined relative importance raw pira investigated role relapses allcause disability worsening using andersengill models observed impact mechanism worsening disease modifying therapies dmts time reach milestone disability levels using time continuous markov models pira started early multiple sclerosis occurred phenotypes became principal driver disability accumulation progressive phase disease relapses significantly increased hazard allcause disability worsening events following year relapses occurred vs year without relapses hazard increased 3148 p 0001 preexisting disability older age principal risk factors incomplete relapse recovery placebotreated patients minimal disability edss 1 took 895 years increased limitation walking ability edss 4 1848 years require walking assistance edss 6 treating patients dmts delayed times significantly 351 years 95 confidence limit 319 396 309 years 260 372 respectively relapsingremitting multiple sclerosis rrms patients worsened exclusively due raw events took similar time reach milestone edss values compared pira events fastest transitions observed patients pira superimposed relapses data confirm relapses contribute accumulation disability primarily early multiple sclerosis pira starts already rrms becomes dominant driver disability accumulation disease evolves preexisting disability older age principal risk factors disability accumulation using dmts delays disability accrual years potential gain time highest earliest stages multiple sclerosispmid35104840 doi101093 brain awac016,0.0
accumulation meningeal lymphocytes correlates white matter lesion activity progressive ms jci insight 2022 feb 1e151683 doi 101172 jciinsight151683 online ahead printabstractsubpial cortical demyelination important component multiple sclerosis ms pathology contributing disease progression yet mechanism s underlying development remain unclear compartmentalized inflammation involving meninges may drive type injury given recent findings identifying substantial white matter wm lesion activity patients progressive ms elucidating whether wm lesional activity relates meningeal inflammation subpial cortical injury interest using postmortem formalinfixed paraffinembedded tissue blocks range 572 blocks median 30 blocks 27 progressive ms patients assessed relationship meningeal inflammation extent subpial cortical demyelination state subcortical wm lesional activity meningeal accumulations t cells b cells myeloid cells spatially adjacent subpial cortical lesions greater immunecell accumulation associated higher subpial lesion numbers patients higher extent meningeal inflammation harboured greater proportion active mixed activeinactive wm lesions overall lower proportion inactive remyelinated wm lesions findings support involvement meningeal lymphocytes subpial cortical injury also point potential link inflammatory subpial cortical demyelination pathological mechanisms occurring subcortical white matterpmid35104246 doi101172 jciinsight151683,1.0
myotubularinrelated protein protects neuronal degeneration mediated oxidative stress infection j biol chem 2022 jan 28101614 doi 101016 jjbc2022101614 online ahead printabstractmicrobial infections linked onset severity neurodegenerative diseases amyotrophic lateral sclerosis multiple sclerosis alzheimers disease underlying mechanisms remain largely unknown used genetic screen genes involved protection infectionassociated neurodegeneration identified gene mtm10 validated role encoded myotubularinrelated protein mtm10 protecting dendrites caenorhabditis elegans degeneration mediated oxidative stress pseudomonas aeruginosa infection experiments indicated mtm10 expressed awc neurons c elegans functions cellautonomous manner protect dendrite degeneration caused pathogen infection also confirm changes observed dendrites animals due premature death overall sickness finally studies indicated mtm10 functions awc neurons preserve chemosensation following pathogen infection results reveal essential role myotubularinrelated protein 10 protection dendrite morphology function deleterious effects oxidative stress infectionpmid35101447 doi101016 jjbc2022101614,0.0
primary progressive multiple sclerosis portuguese patient neurofibromatosis type 1 cureus 2021 dec 21 13 12 e20561 doi 107759 cureus20561 ecollection 2021 decabstractneurofibromatosis type 1 nf1 frequent genetic neurocutaneous syndrome multiple sclerosis ms acquired demyelinating disease central nervous system association diseases rare case report describe 25yearold man gait impairment upper limbs tremor slurred speech urinary symptoms form urinary urgency incontinence symptoms started year earlier progressive course examination revealed scattered cafaulait spots right ptosis bilateral horizontal vertical nystagmus mild dysarthria quadriparesis generalized hyperreflexia bilateral babinski signs upper limb tremor bilateral proprioceptive errors bilateral appendicular dysmetria severe gait ataxia brain mri showed lesions involving deep subcortical white matter well thalami enhancement administration gadolinium suggestive focal areas signal intensity fasi setting nf1 also oval lesions periventricular white matter perpendicular ventricles involving corpus callosum atypical fasi spinal mri also demonstrated several lesions mildly enhance administration gadolinium cerebrospinal fluid csf examination revealed mild lymphocytic pleocytosis 18 l mildly elevated protein 053 g l normal glucose positive oligoclonal igg bands extensive laboratory workup including microbiological csf studies aquaporin4igg myelinoligodendrocyte glycoproteinigg autoimmune screening viral serology negative genetic study revealed new mutation nf1 gene previously reported intend discuss genetic autoimmune mechanisms ms nf1 appear related draw attention association timely diagnosis ms important prevent disability nf1 patientspmid35103140 pmcpmc8771896 doi107759 cureus20561,1.0
effects neurodynamic interventions pain sensitivity function patients multiple sclerosis randomized clinical trial physiotherapy 2021 apr 22 1153645 doi 101016 jphysio202104004 online ahead printabstractobjective assess effects adding neurodynamic intervention multimodal management approach individuals multiple sclerosis ms upper extremity pain symptomsdesign randomized clinical trialsetting tertiary hospital centerparticipants thirtytwo individuals ms randomly assigned multimodal usual care alone n16 multimodal usual care plus neurodynamic intervention n16 interventions groups received 5 sessions multimodal usual care 30minutes duration twice per week subjects allocated neurodynamic group also received bilateral neurodynamic slider interventions targeting upper extremity nerve trunksoutcome measures pressure pain thresholds ppts radial median ulnar nerve trunks second metacarpal tibialis anterior pain intensity upper extremity nprs 010 light touch detection threshold von frey hairs manual dexterity ninehole peg test assessed interventionresults subjects receiving neurodynamic interventions experienced larger improvements ppts locations moderate effect size betweengroups differences 895 1865kpa higher decrease pain intensity rest large effect difference 17 95ci 04 30 improvements sensitivity light touch moderate effect difference 07 95ci 13 01 manual dexterity large effect difference 77 95ci 40 114seconds receive neurodynamic interventionconclusions inclusion neural mobilization multimodal management approach resulted reduction pressure sensitivity greater reduction pain improvement sensitivity light touch manual dexterity ms studies necessary confirm findings longer term followups clinicaltrialsgov nct03595631 pmid35101724 doi101016 jphysio202104004,0.0
association early mri characteristics subsequent epilepsy neurodevelopmental outcomes children tuberous sclerosis complex neurology 2022 jan 31101212 wnl0000000000200027 doi 101212 wnl0000000000200027 online ahead printabstractbackground objective multiple factors found contribute high risk epilepsy infants tuberous sclerosis complex tsc including evolution eeg abnormalities tsc gene mutation mri characteristics aim present prospective multicenter study 1 identify early mri biomarkers epilepsy infants tsc aged 6 months seizure onset 2 associate mri biomarkers neurodevelopmental outcomes 2 years age study part epistop projectmethods evaluated brain mris performed infants tsc younger 6 months age used harmonized mriprotocols across centers children monitored closely neuropsychological evaluation serial video eeg mri characteristics defined tubers radial migration lines white matter abnormalities cysts calcifications subependymal nodules sen subependymal giant cell astrocytoma sega visually evaluated lesions detected semiautomatically lesion brain volume ratios calculated associated epilepsy neurodevelopmental outcomes two yearsresults lesions assessed mris 77 tsc infants 62 mris sufficient volume analysis presence tubers higher tuberbrain ratios associated development clinical seizures independently tsc gene mutation preventive treatment furthermore higher tuberbrain ratios associated lower cognitive motor development quotients two years independently tsc gene mutation presence epilepsydiscussion infants tsc significant association characteristic tsc lesions detected early brain mri development clinical seizures well neurodevelopmental outcomes first two years life according results early brain mri findings may guide clinical care young children tscclassification evidence study provides class evidence infants tsc significant association characteristic tsc lesions early brain mri development clinical seizures neurodevelopmental outcomes first two years lifepmid35101906 doi101212 wnl0000000000200027,0.0
comparing humoral immune response sarscov2 vaccines multiple sclerosis healthy controls austrian prospective multicenter cohort study eur j neurol 2022 feb 1 doi 101111 ene15265 online ahead printabstractbackground sarscov2 vaccination recommended patients multiple sclerosis pwms response may limited diseasemodifyingtreatments dmt objective compare rate humoral immune response safety sarscov2 vaccines pwms healthy controls hc methods multicenter prospective study 456 pwms 116 hc sarscov2igg response measured 3 months first vaccine dose primary endpoint defined proportion patients developing antibodies seroconversion secondary endpoints included antibody level safety efficacyresults compared 974 hc seroconversion occurred 967 88 91 untreated pwms 971 135 139 immunomodulatory imdmt 611 138 226 p0001 immunosuppressive dmt isdmt seroconversion lowest anticd20 monoclonal antibodies cd20mab 526 followed sphingosine1phosphatereceptormodulators s1pm 636 s1pmsubgroup seroconversion increased lymphocyte count 131 per 01 g l p0035 pwms cd20mab bcell depletion decreased seroconversion 052 p0038 whereas time since last dmt safety sarscov2 vaccines pwms excellentconclusions humoral response sarscov2 vaccines pwms generally excellent reduced isdmt importantly bcell depleting cd20mab s1pm seroconversion still expected majority patients sarscov2 vaccination offered every ms patientpmid35102646 doi101111 ene15265,0.0
management bladder dysfunction multiple sclerosis systematic review metaanalysis studies regarding bladder rehabilitation eur j phys rehabil med 2022 feb 1 doi 1023736 s1973908722072173 online ahead printabstractintroduction aim study investigate efficacy rehabilitation programs bladder disorders patients multiple sclerosis ms guide physicians delineating therapeutic tools programs physiatrists using best current strategiesevidence acquisition search conducted pubmed embase cochrane library web science studies eligible included adults bladder disorders related ms described specific treatments rehabilitation interest search identified 190 283 articles using keywords multiple sclerosis rehabilitation urinary bladder reviewers analyzed 81 fulltexts 21 publications met criteria included systematic reviewevidence synthesis systematic review identified specific rehabilitation treatments reported current literature metaanalysis compared scores scales used quantify bladder disorders due ms rehabilitation comparison control groupconclusions present study suggests need specific therapeutic protocol based degree disability symptom complexity patients msrelated neurogenic lower urinary tract dysfunction nlutd particularly metaanalysis shows effectiveness peripheral tibial nerve stimulation ptns pelvic floor muscle training pfmt neurogenic detrusor overactivity ndo however goal physiotherapy treat incontinence without making urinary retention worse viceversa reducing loss urine urgency ensuring emptying bladderpmid35102733 doi1023736 s1973908722072173,0.0
tdp43 pathology noxious assembly therapeutic removal prog neurobiol 2022 jan 28102229 doi 101016 jpneurobio2022102229 online ahead printabstractour understanding amyotrophic lateral sclerosis frontotemporal dementia advanced dramatically since discovery cytoplasmic tar dnabinding protein 43 tdp43 inclusions hallmark pathology neurodegenerative diseases recent studies provided insights physiological function tdp43 essential dna rnamodulating protein triggers consequences tdp43 dysfunction aggregation formation tdp43 pathology progressive process involving generation multiple distinct protein species varying biophysical properties roles neurodegeneration explore pathogenic changes tdp43 including mislocalisation misfolding aberrant liquidliquid phase separation stress granule assembly oligomerisation posttranslational modification drive diseaseassociation aggregation tdp43 proteinopathies highlight pathological tdp43 species formed contribute cellular dysfunction toxicity via lossoffunction gainoffunction mechanisms also review role protein homeostasis mechanisms namely ubiquitin proteasome system autophagylysosome pathway heatshock response chaperonemediated autophagy combating tdp43 aggregation discuss dysfunction likely promotes disease pathogenesis progression finally evaluate preclinical studies aimed enhancing tdp43 protein clearance via mechanisms provide insight promising strategies future therapeutic advances harnessing mechanisms protect ameliorate tdp43 pathology presents promising opportunities developing diseasemodifying treatments neurodegenerative diseasespmid35101542 doi101016 jpneurobio2022102229,0.0
highdensity lipoprotein reduces microglia activation protects experimental autoimmune encephalomyelitis mice int immunopharmacol 2022 jan 28 105108566 doi 101016 jintimp2022108566 online ahead printabstractstudies shown highdensity lipoprotein hdl powerful antiatherosclerosis factor vivo vitro antiinflammatory effects also plays important role immune system central nervous system cns study bv2 microglia inflammation model experimental autoimmune encephalomyelitis animal model used investigate potential mechanism hdl multiple sclerosis results show hdl inhibits activation bv2 microglia model bv2 microglia inflammation validated primary microglia hdl can downregulate expression tnf il6 inos western blot results showed hdl reduce expression levels tlr4 cd14 myd88 nfb p65 lpsinduced microglia mouse model experimental autoimmune encephalomyelitis hematoxylineosin staining showed decreased infiltration inflammatory cells brain spinal cord tissues luxol fast blue lfb staining showed significant improvement spinal cord demyelination found hdl reduced spinal cord brain inflammation eae induction inhibited infiltration cd68 iba1 positive inflammatory cells reduced production multiple proinflammatory cytokines including proinflammatory cytokines tnf il6 il1 western blot showed eae mice hdl inhibited activation erk1 2 jnk mapk pathway pib p65 nfb pathway taken together study suggests hdl may influence microglia activation inflammatory response mice regulating inflammatory signaling pathways improving induction experimental autoimmune encephalomyelitis animal model multiple sclerosis provides insights hdl therapy multiple sclerosispmid35101849 doi101016 jintimp2022108566,1.0
evaluation program training psychologists acceptance commitment therapy resilience intervention people multiple sclerosis singlearm longitudinal design nested qualitative study disabil rehabil 2022 feb 1113 doi 101080 0963828820222025926 online ahead printabstractpurpose singlearm longitudinal study evaluated effectiveness program training psychologists delivering acceptance commitment therapybased program resilience activities every day ready people multiple sclerosis pwms materials methods training encompassed three phases 1 training workshop 2 ready participation 3 ready delivery pwms selfreport data collected immediately workshop participation ready 3 15month followupsresults forty psychologists successfully completed training training effective fostering acquisition knowledge skills effective delivery ready pwms participants improved course training resilience positive affect wellbeing psychological flexibility associated processes improvements peaked participation ready phase continued accrue slower rate three months later psychological flexibility mediated improvements resilience positive affect wellbeing qualitative data confirmed personal professional multiple sclerosis ms psychologist community level positive training impactsconclusions training fostered positive professional personal development trainees consolidated integration ready frontline service pwms date 50 ready groups pwms conducted italyimplications rehabilitationtraining psychologists delivering acceptance commitment therapy act based resilience intervention people multiple sclerosis ms associated positive personal professional impacts traineesthe training program strengthened sense community among members professional network attended traineesin act training psychological flexibility plays key role improving resilience positive affect wellbeing trainees therefore important intervention targetact training practitioners fosters integration actbased interventions frontline servicespmid35100924 doi101080 0963828820222025926,0.0
anaplastic thyroid carcinoma unusual longterm survival case report background anaplastic thyroid carcinoma rare rapidly progressive highly aggressive tumor global annual incidence 12 per million people mostly affects older adults women median survival duration diagnosis exceed 68 monthscase presentationa 60yearold female patient mixed race honduran presented local medical service dysphonia started approximately 2 months earlier accompanied orthopnea started 1 month earlier physical examination soft mass palpated within anterior neck region approximately 4 cm diameter painless mobile swallowing irregular margins ultrasound computed tomography neck performed subsequently fine needle aspiration biopsy performed histological diagnosis anaplastic thyroid carcinoma stage ivb underwent total thyroidectomy chemotherapy currently fifth year remission diagnosis remains oncologic surveillancediscussionanaplastic thyroid carcinoma demonstrates lethal behavior approximately 18 survive year diagnosis 010 survive 5 years different pretherapeutic prognostic factors may affect survival including age 70 years absence distant metastases complete local resectionconclusionconventional treatment improves quality life patient results encouraging medium long term patients manage exceed average life expectancy 36 months despite undergoing currently available therapeutic regimen,0.0
trait mindfulness emotion dysregulation depression individuals multiple sclerosis abstractobjectives emotion dysregulation plays role development maintenance psychopathology given higher rates mood disturbances people multiple sclerosis pwms need explore relationships metrics emotion dysregulation potential protective traits mindfulness multifaceted trait characteristic reflecting present moment awareness one trait showing promise positive associations affective health current project assessed relationship trait mindfulness use emotion regulation strategies emotionally evocative task depression pwmsmethods sixtyone pwms completed worry rumination induction task examined emotion regulation strategy use response emotionally evocative stimuliresults higher trait mindfulness associated lower symptoms depression greater employment acceptancebased strategies following worry rumination inductions acceptance use mediated relationship trait mindfulness symptoms depressionconclusions results suggest association trait mindfulness emotion dysregulation extends use emotion regulation strategies emotionally evocative task additionally emotion regulation strategy use acceptance particular may play role relationship trait mindfulness depression findings suggest increasing levels mindfulness clinical interventions may present path toward improving emotion regulation extension reducing symptoms depression pwms,0.0
glucosylceramide synthase inhibition reduces ganglioside gm3 accumulation alleviates amyloid neuropathology stabilizes remote contextual memory mouse model alzheimers disease background gangliosides highly enriched brain critical normal development function however rare neurometabolic diseases deficiency lysosomal ganglioside hydrolysis pathogenic leads earlyonset neurodegeneration neuroinflammation demyelination dementia increasing evidence also suggests subtle ganglioside accumulation contributes pathogenesis common neurological disorders including alzheimers disease ad notably ganglioside gm3 levels elevated brains ad patients several mouse models ad plasma gm3 levels positively correlate disease severity ad patientsmethodstg2576 ad model mice fed chow formulated small molecule inhibitor glucosylceramide synthase gcsi determine whether reducing glycosphingolipid synthesis affected aberrant gm3 accumulation amyloid burden disease manifestations cognitive impairment gm3 measured lcms amyloid burden elisa amyloid red staining memory assessed using contextual fear chamber testresultsgcsi mitigated soluble a42 accumulation brains ad model mice treatment started prophylactically remarkably gcsi treatment also reduced soluble a42 levels amyloid plaque burden aged ie 70 weeks old ad mice preexisting neuropathology analysis contextual memory tg2576 mice showed impairments remote corticaldependent memory consolidation preceded deficits shortterm hippocampaldependent contextual memory consistent soluble a42 accumulation occurring rapidly cortex ad mice compared hippocampus notably gcsi treatment significantly stabilized remote memory consolidation ad miceespecially mice enhanced cognitive training finding consistent gcsi treatment lowering aberrant gm3 accumulation cortex ad miceconclusionscollectively results indicate glycosphingolipids regulated gcs important modulators neuropathology glycosphingolipid homeostasis plays critical role consolidation remote memories,1.0
efficiency safety umbilical cord mesenchymal stromal stem cells multiple sclerosis combined treatment summarymultiple sclerosis demyelinating disease nervous system affects young people working age quickly leads disability treatment pathology umbilical cord mesenchymal stem cells promising given immunomodulatory neurotrophic properties study involved 27 patients diagnosed multiple sclerosis 12 underwent combined treatment intravenous intrathecal administration umbilical cord multipotent mesenchymal stromal stem cells effectiveness treatment determined degree neurological deficit spasticity combined treatment umbilical cord mesenchymal stem cells significantly improves condition patients multiple sclerosis promotes regression neurological deficits spasticity treatment safe deeper study necessary continue research areakey words multipotent mesenchymal stem stromal cells multiple sclerosis safetyintroductionmultiple sclerosis demyelinating disease central nervous system multifactorial etiology pathogenesis accompanied rapid disability patients mostly young working age abi chahine lu 2020 baecherallan et al 2018 etiology ms considered influence adverse environmental factors genetic predisposition organism defects leukocyte antigen system hla beeravolu et al 2017 adverse factors may viral bacterial infection insufficient insolation vitamin d deficiency canto oksenberg 2018 cheng et al 2019 feige et al 2020 pathogenesis ms leading place belongs immunopathological reactions form imbalance subpopulations t lymphocytes disorders complement system accumulation proinflammatory mediators followed process axonal degeneration apoptosis glia cells result persistent neurological deficit fernndez et al 2018 remyelination processes occur patient clinically remitting type disease comparison demyelination processes much weaker gugliandolo et al 2020 due complexity pathogenesis multifactorial etiology also single effective approach treatment ms one promising approaches treatment ms use mesenchymal stromal stem cells mscs various origins mansoor et al 2019 lubetzki et al 2020 expediency approach substantiated number experimental works ranjbaran et al 2018 marrodan et al 2019 well clinical studies indicate safety ms treatment mscs riordan et al 2018 solomon 2019 tarlinton et al 2020 issues clinical effect dynamics neurological deficit combined use stem cells patients ms remain unresolved optimal source msc umbilical cord cells younger number mutations msc adult body uccelli et al 2019 zeydan kantarci 2020 use autologous mscs patients autoimmune diseases debatable issue also defective exhibit immunomodulatory properties relative recipient effectiveness mscs questionable toluvani 2019 aim study investigate efficiency safety combined umbilical cord multipotent mesenchymal stromal stem cells treatment multiple sclerosismaterial methodthe study performed basis reconstructive neurosurgery department xray surgery state institution romodanov neurosurgery institute nams ukraine frame scientific research work investigate effectiveness regenerative cell technologies neurosurgical treatment patients demyelinating diseases cns cerebral palsy 0119u000112 study approved meeting committee bioethics state institution romodanov neurosurgery institute nams ukraine 1 170120 informed consent participate study signed patients criteria inclusion patients study 1 age patients 18 55 years 2 verified diagnosis ms according mcdonalds criteria 2010 3 number points edss scale 1 75 deterioration neurological status 1 point edss scale last year indicating progression disease 4 lack effect treatment diseasemodifying drugs 5 fact treatment monoclonal antibodies 6 signed informed consent participate study criteria noninclusion patients study 1 pregnancy 2 contractures limbs 3 severe concomitant somatic pathology heart failure according nyha iiiiv centuries myocardial infarction renal failure glomerular filtration rate 59 ml min cachexia 4 acute infectious process body t 372 c positive pcr test covid19 4 mental disorders 5 malignant neoplasmsucmscs isolation cultivation phenotyping protocol ucmscs study prepared llc medical biotechnology company hemafund within framework agreement scientific practical cooperation dated 051119 umbilical cords obtained healthy fullterm infants signing informed consent parentsumbilical cords n3 stored aseptic conditions 2 days 4 c sterile physiological saline ps 09 w v sodium chloride processing isolate ucmscs umbilical cord placed sterile petri dishes washed ps supplemented 5 antibioticantimycotic solution sigma usa umbilical cord tissue cleaned blood clots cut pieces explants approximately 11 5 cm explants placed 75 cm2 culture flasks 12 explants per flask culture medium added flask cultural medium consisting dulbeccos modified eagles medium nutrient mixture f 12 ham dmemf12 gibco containing 5 fetal bovine serum capricorn germany 2 mm lglutamine capricorn germany 1 g ml amphotericin capricorn germany explants cells cultured 23 weeks culture medium change every 23 days humid co2 incubator 5 co2 air +37 cafter 8 days tissue inspected phase contrast light microscope monitor cell migration cells first passaged 80 confluency monolayer achieve cells detached surface flask 005 trypsinedta sigma usa transferred 175 cm2 culture flasks seeding 4 5x103cells cm2 density cultivated another 23 passagethe mscs derived umbilical cord displayed typical fibroblastic morphology fig 1 b administration 2nd fig 1 b 3rd passage ucmsc used percentage viable ucmscs cell suspension estimated flowmetry 9393 079 n3 uc mscs isolated human umbilical cord analysed surface marker expression profile passage 2nd cd34 cd45 cd19 hladr cd73 cd90 cd105 cultured mscs known strongly positive expression cd73 9953 013 cd90 9980 006 cd105 9953 023 negative expression cd34 0 cd45 00 cd19 0 hladr 001 001 due minimal criteria established mesenchymal tissue stem cell committee international society cellular therapyucmsc also tested differentiation adipocytes chondroblasts osteoblasts vitro using stained oil red alcian blue alizarin red respectivelyfig 1 phase contrast image mscs emerging umbilical cord tissue piece explant morphology ucmscs passage 0 eviction cells explant white arrows scale bar 100m b morphology ucmscs passage 2nd scale bar 100 mm treatment protocol patients n 27 underwent general examination well set laboratory instrumental examinations included general blood test general urine test biochemical blood test glucose bilirubin urea creatinine alt ast cholesterol immunogram determination level neuroautoantibodies mri brain cervical spine contrast enhancement electroencephalography eeg electroneuromyography enmg transcranial magnetic stimulation tms visual evoked potentials special consultations patients divided two groups according type clinical course group 1 9 patients diagnosed progressiveremitting 75 type disease 3 primary progressive 25 mean age patients group 1 3525 1372 years patients group 1 n 12 treated cultured umbilical cord mesenchymal stem cells ucmscs quality characteristics patients group 1 received total dose ucmscs rate 1 106 kg body weight 20 106 administered intrathecally rest material intravenously intrathecal administration performed according typical method performing lumbar puncture compliance rules asepsis antiseptics manipulation room using local anesthesia previously comparison group group 2 n 15 whose patients treated according multiple sclerosis treatment protocol mean age patients group 2 398 1023 years according type clinical course 12 patients progressiveremitting type course 80 2 primaryprogressive 134 1 secondaryprogressive 66 criteria inclusion noninclusion study given key observation points 1 month 6 months 1 year starting point observation period considered day ucmscs administration reintroduction ucmscs performed 6 months first procedure followup examinationobjective assessment clinical condition patients performed extended scale assessment degree disability according kurtzke expanded disability status scale edss spasticity assessed ashworth scalestatistical data processing statistica 100 software package licensed software used statistical data processing reliability difference indicators determined using students t test value p005 considered statistically significantresults discussionthe mean age patients group 1 3525 1372 group 2 398 1023 average duration disease time hospitalization department patients groups n 27 68 years predominant number patients women group 1 ratio women men 8 4 group 2 9 6 mean edss group 1 5583 1346 hospitalized 1 month ucmcss treatment statistically significant dynamics edss observed 5375 1245 p 0169 significant positive dynamics edss scale observed 6 months treatment 4583 0973 compared value treatment p 0024 1 month treatment p 0031 also significant difference value edss 1 year first treatment ucmscs 4208 0891 compared pretreatment p 0003 well indicators 1 month p 0003 6 months p 00007 group 2 mean edss score treatment 58 1293 1 month indicator 5433 1163 p 0011 6 months 5567 0799 p 0278 1 year 56 091 p 0239 statistically significant difference dynamics influence treatment comparing groups 1 2 statistically significant difference found edss index hospitalization p 0337 1 month treatment ucmscs p 0485 difference groups observed 6 weeks treatment p 0003 1 year p 00002 assessing spasticity patients group 1 mean value ashworth scale treatment 175 dynamics 1 month administration uc mscs average value scale 141 statistically insignificant p 0317 positive dynamics detected 6 months similar dynamics neurological deficit edss scale compared first month followup mean spasticity score 1 difference statistically significant compared pre treatment p 0008 1 year first injection uc mscs 6 months second decrease spasticity average value 083 p 0001 assessing spasticity patients group 2 mean value ashworth scale treatment 18 1 month treatment muscle relaxants mean value scale 154 statistically significant p 002 6 months compared first month followup mean score spasticity group 2 1 difference statistically insignificant compared pretreatment p 0066 1 year treatment decrease spasticity average value 1 p 0063 fig 2 fig 2 dynamics edss patients ms comparison rate spasticity two groups patients different time intervals difference treatment found p 0468 fig 3 first month treatment 2 groups difference statistically significant p 0426 6 months statistically significant difference groups found p 05 reduction spasticity statistically significant observed 1 year favor group 1 first application ucmscs p 004 results indicate improvement neurological status first month treatment patients ucmscs positive effect observed 6 months treatment continued increase dynamics 1 year suggests need extend observation period determine effectiveness ucmscs remote period regression spasticity occurs little later 6 months difference group 1 according ashworth scale dynamics statistically significant significant reduction spasticity observed time point corresponding 1 year first application 6 months second application obtained data consistent data authors toluvani tarlinton et al regarding peculiarities effect ucmscs course autoimmune process probably due immunomodulatory effect group 1 4 12 34 patients headache procedure alleviated taking nonsteroidal anti inflammatory drugs passed completely 812 hours 3 25 patients rise body temperature 386 c recorded also acquired symptomatic therapy among reactions msc administration general weakness observed first week treatment 8 12 67 patients underwent specific treatment data obtained allow us speak safety procedure need research large groups patients main disadvantages study small sample patients relatively short observation time however monitoring patients continues determine longterm effects sustainability positive effectfig 3 dynamics spasticity ashworth scale patients ms conclusionscombined treatment umbilical cord mesenchymal stem cells significantly improves condition patients multiple sclerosis contributes regression neurological deficits 2 umbilical cord mesenchymal stem cells significantly reduce spasticity improve motor function multiple sclerosis 3 treatment ucmsc safe reactions use shortlived require specific therapy,1.0
patient multiple sclerosis developed bilateral optic neuritis central trigeminal myelin lesion rinsho shinkeigaku 2022 jan 31 doi 105692 clinicalneurolcn001658 online ahead printabstracta 70yearold woman admitted hospital due bilateral optic neuritis left facial sensory disturbance became exacerbated 10 days serum cerebrospinal fluid csf negative aquaporin 4 antibody myelin oligodendrocyte glycoprotein antibody high level myelin basic protein mbp csf observed brain mri showed high t2 signal contrast enhancement bilateral optic nerve intramedullary tract central myelin lesion trigeminal nerve intravenous methylprednisolone pulse therapy visual impairment facial sensory disturbance gradually improved diagnosed clinically isolated syndrome based 2017 mcdonald criteria diagnosis multiple sclerosis ms suspected due trigeminal myelin lesion confined central myelin portion high level mbp csf treatment dimethyl fumarate effective preventing recurrence 13 months patient centralperipheral myelin transitional zone trigeminal nerve located 16 mm pons central myelin changes peripheral myelin patient showed high t2 signal trigeminal nerve 3 mm pons mri suggesting involvement central trigeminal myelin lesion findings central trigeminal myelin lesion mri may aid differentiating ms seronegative neuromyelitis optica spectrum disorderpmid35095049 doi105692 clinicalneurolcn001658,1.0
update optic neuritis international view neuroophthalmology 2021 aug 31 46 1 118 doi 101080 0165810720211964541 ecollection 2022abstractpreviously optic neuritis thought typical ie idiopathic multiple sclerosis ms related associated good visual prognosis atypical ie associated ms requiring corticosteroids plasma exchange vision recover recently importance optic neuritis neuromyelitis optica spectrum disorder myelin oligodendrocyte glycoprotein mog antibody disease become appreciated results optic neuritis treatment trial ontt influenced optic neuritis treated around world review surveyed international literature optic neuritis adults aims first find reported incidence optic neuritis different countries ascertain percentage cases seropositive antiaquaporin 4 antimog antibodies second document presenting features treatment outcomes first episode different types optic neuritis countries compare results outcomes ontt cohort data sought highlight ambiguities currently lie manage optic neuritis made recommendations future treatment trials optic neuritis carried current antibody testing erapmid35095131 pmcpmc8794242 doi101080 0165810720211964541,1.0
tim3 relieves experimental autoimmune encephalomyelitis suppressing mhcii front immunol 2022 jan 13 12770402 doi 103389 fimmu2021770402 ecollection 2021abstracttim3 immune checkpoint inhibitor widely expressed immune cells contributes immune tolerance however mechanisms tim3 induces immune tolerance remain determined major histocompatibility complex ii mhcii plays key role antigen presentation cd4+t cell activation dysregulated expressions tim3 mhcii associated pathogenesis many autoimmune diseases including multiple sclerosis demonstrated suppressing mhcii expression macrophages via stat1 ciita pathway tim3 inhibits mhciimediated autoantigen presentation cd4+t cell activation result overexpression blockade tim3 signaling mice experimental autoimmune encephalomyelitis eae inhibited increased mhcii expression respectively finally altered clinical outcomes thus identified new mechanism tim3 induces immune tolerance vivo regulating tim3mhcii signaling pathway expected provide new solution multiple sclerosis treatmentpmid35095844 pmcpmc8793033 doi103389 fimmu2021770402,0.0
pain multiple sclerosis understanding pathophysiology diagnosis management clinical vignettes front neurol 2022 jan 13 12799698 doi 103389 fneur2021799698 ecollection 2021abstractneuropathic pain pain syndromes occur vast majority patients multiple sclerosis time disease course pain can become chronic paroxysmal review will utilize clinical vignettes describe various pain syndromes associated multiple sclerosis pathophysiology syndromes vary central neuropathic pain lhermittes phenomenon associated central nervous system lesions trigeminal neuralgia optic neuritis pain associated nerve lesions muscular pain can also arise due spasticity addition will discuss strategies utilized help patients manage symptomspmid35095742 pmcpmc8794582 doi103389 fneur2021799698,0.0
dna methylation changes glial cells normalappearing white matter multiple sclerosis patients epigenetics 2022 jan 30120 doi 101080 1559229420212020436 online ahead printabstractmultiple sclerosis ms leading cause nontraumatic neurological disability young adults chronic inflammatory neurodegenerative disease central nervous system cns due poor accessibility target organ cnsconfined processes underpinning later progressive form ms remain elusive thereby limiting treatment options aimed examine dna methylation stable epigenetic mark genome activity glial cells capture relevant molecular changes underlying ms neuropathology profiled dna methylation nuclei nonneuronal cells isolated 38 postmortem normalappearing white matter nawm specimens ms patients n 8 comparison white matter control individuals n 14 using infinium methylationepic beadchip identified 1 226 significant genomewide adjusted pvalue 005 differentially methylated positions dmps ms patients controls functional annotation altered dmpgenes uncovered alterations processes related cellular motility cytoskeleton dynamics metabolic processes synaptic support neuroinflammation signaling wnt tgf pathways fraction affected genes displayed transcriptional differences brain ms patients reported publically available transcriptomic data cell typerestricted annotation dmpgenes attributed alterations cytoskeleton rearrangement extracellular matrix remodelling glial cell types processes including ion transport wnt tgf signaling immune processes specifically linked oligodendrocytes astrocytes microglial cells respectively findings strongly suggest nawm glial cells highly altered even absence lesional insult collectively exhibiting multicellular reaction response diffuse inflammationpmid35094644 doi101080 1559229420212020436,0.0
effect deep brain stimulation cerebellar tremor compared noncerebellar tremor using wearable device patient multiple sclerosis case report front hum neurosci 2022 jan 13 15754091 doi 103389 fnhum2021754091 ecollection 2021abstracttremor upper extremity significant cause disability patients multiple sclerosis ms ms tremor complex contains ataxic intentional tremor component due involvement cerebellum cerebellar outflow pathways ms plaques makes ms tremor general less responsive medications deep brain stimulation dbs associated essential tremor parkinsons disease cerebellar component thought main reason making dbs less effective although clear whether due lack suppression ataxic tremor dbs else goal study clarify effect dbs cerebellar tremor compared noncerebellar tremor patient ms wearing accelerometer index finger hand able quantitatively characterize kinetic tremor frequency amplitude cerebellar ataxia component one hand without cerebellar component hand beginning end hand movement approaching target dbs status found cerebellar tremor surprisingly good response dbs tremor without cerebellar component function control cerebellar tremor good due distal oscillation made amplitude tremor increasingly greater approached target explains cerebellar tremor ms tremor cerebellar component poor functional transformation even good percentage tremor control case study provides better understanding effect dbs cerebellar tremor ms tremor using wearable device help future studies improve patient selection outcome prediction dbs treatment disabling tremorpmid35095448 pmcpmc8792598 doi103389 fnhum2021754091,0.0
diseasemodifying drug uptake health service use ageing ms population front immunol 2022 jan 13 12794075 doi 103389 fimmu2021794075 ecollection 2021abstractbackground evidence regarding efficacy effectiveness diseasemodifying drugs dmds older multiple sclerosis ms population scarce contributed lack evidencebased treatment recommendations ageing ms population practice guidelines examined relationship age 55 55 years dmd exposure health service use ms populationmethods conducted populationbased observational study using linked administrative health data british columbia canada selected persons ms followed recent first ms demyelinating event 18th birthday 01january1996 index date earliest emigration death 31december2017 study end assessed dmd exposure status time initially versus dmd generation first second finally individual dmd agespecific analyses conducted allcause hospitalizations number physician visits assessed using proportional means model negative binomial regression generalized estimating equationsresults included 19 360 persons ms 72 women 10 741 19 360 56 ever reached 55th birthday personyears followup whilst aged 55 132 283 93 594 whilst aged 55 dmd versus dmd 55yearolds associated 23 lower hazard hospitalization adjusted hazard ratio ahr077 95ci 072082 55yearolds ahr095 95ci 087104 similar patterns observed first second generation dmds exposure versus dmd associated rates physician visits either age group 55 years adjusted rate ratio arr102 95ci 100104 55 years arr100 95ci 096103 variation arr observed across individual dmdsconclusion study showed beneficial effects dmds used treat ms hospitalizations aged 55 time exposure contrast individuals 55 years age exposed dmd hazard hospitalization significantly lowered study contributes broader understanding potential benefits risks dmd use ageing ms populationpmid35095869 pmcpmc8792855 doi103389 fimmu2021794075,1.0
singlecell transcriptome profiling unravels distinct peripheral blood immune cell signatures rrms mog antibodyassociated disease front neurol 2022 jan 14 12807646 doi 103389 fneur2021807646 ecollection 2021abstractrelapsingremitting multiple sclerosis rrms myelin oligodendrocyte glycoprotein mog antibodyassociated disease mogad inflammatory demyelinating diseases central nervous system cns due shared clinical manifestations detection diseasespecific serum antibody two diseases currently considered gold standard diagnosis however serum antibody levels unpredictable different stages two diseases herein peripheral blood singlecell transcriptome used unveil distinct immune cell signatures two diseases aim provide predictive discrimination singlecell rna sequencing scrnaseq conducted peripheral blood three subjects ie one patient rrms one patient mogad one patient healthy control results showed cd19+ cxcr4+ naive b cell subsets significantly expanded rrms mogad verified flow cytometry importantly rrms singlecell transcriptomic characterized increased naive cd8+ t cells cytotoxic memorylike natural killer nk cells together decreased inflammatory monocytes whereas mogad exhibited increased inflammatory monocytes cytotoxic cd8 effector t cells coupled decreased plasma cells memory b cells collectively findings indicate two diseases exhibit distinct immune cell signatures allows highly predictive discrimination two diseases paves novel avenue diagnosis therapy neuroinflammatory diseasespmid35095746 pmcpmc8795627 doi103389 fneur2021807646,1.0
central fibrous areas changes glomerular vascular pole lesions associated age disease int urol nephrol 2022 jan 31 doi 101007 s11255022031263 online ahead printabstractpurpose central fibrous areas cfas small hyalinotic monotonous nodular areas observed glomerular vascular pole lesions attempted clarify relationship cfa formation age healthy kidneys affected immunoglobulin iga nephropathymethods zerohour biopsy specimens living renal donors 135 cases iga nephropathy biopsy specimens 67 cases collected retrospectively observed biopsy specimen determined total number glomeruli total level glomerulosclerosis number observable glomerular vascular poles number glomeruli cfas serum creatinine level estimated glomerular filtration rate egfr additionally calculated glomerular sclerosis rate gsr vascular pole appearance rate par cfa rate cfar evaluate relationship factors patient ageresults significant negative correlation patient age egfr zerohour p 00001 spearman p 00009 multiple regression hereafter iga p 00022 p 00001 groups zerohour group observed significant positive correlation patient age gsr p 00001 p 00001 however correlation iga group groups significant positive correlation patient age cfar zerohour group p 00003 p 00091 iga group p 00001 p 00004 slope regression line iga group formula also significantly higher zerohour group formula p 001 conclusion findings indicate cfa may useful indicator kidney aging especially patients kidney disease caused iga nephropathypmid35099688 doi101007 s11255022031263,0.0
experiences people multiple sclerosis participating social cognitive behavior change physical activity intervention physiother theory pract 2022 jan 3119 doi 101080 0959398520222030828 online ahead printabstractbackground understanding experiences people ms taking part physical activity interventions critical inform future interventionsaim aim gain insight experiences people ms taking part behavior change group physical activity intervention novel social cognitive theory componentmethods qualitative semistructured interview format utilized questions focussed expectations views beliefs involved study beliefs physical activity subjective evaluation trial content delivery seventeen people interviewed data analyzed using thematic analysisresults three themes generated psychological social factors intervention processes ms identity acceptance ms identity acted initial barrier exercise positive exerciseenabling identity postintervention psychological factors selfefficacy anxiety well social factors social support found play important role participants experienced program similarly intervention processes included support groupbased activities structure exercise classes also interlinked themesconclusion appears groupbased exercise interventions acceptable feasible people ms qualitative findings support previously reported quantitative findings step intervention effective promoting physical activity improving psychological outcomespmid35094662 doi101080 0959398520222030828,0.0
defining routine fatigue care multiple sclerosis united kingdom treatments offered gets mult scler j exp transl clin 2022 jan 20 8 1 20552173211072274 doi 101177 20552173211072274 ecollection 2022 janmarabstractbackground fatigue common disabling multiple sclerosis ms recent metaanalytic systematic review reported 113 trials exercise behavioural interventions fatigue yet patients consistently describe fatigue undertreated extent researchtopractice gap yet documentedobjective describe fatigue treatments people ms pwms united kingdom uk offeredmethods crosssectional survey pwms uk ms register ukmsr data fatigue treatments offered collected using online questionnaire developed patient input summarised using descriptive statistics sociodemographic msrelated psychological factors associated treatment offered evaluated using logistic regression modelresults 4 367 respondents completed survey 903 reported experiencing fatigue 308 reported offered least one type pharmacological nonpharmacological treatment fatigue pharmacological treatments commonly offered 224 compared nonpharmacological treatments 126 29 exercise 59 behavioural therapy logistic regression model older age working shorter time since ms diagnosis lower fatigue associated lower odds offered treatment fatigueconclusion study accentuates extent unmet need fatigue treatment ms ukpmid35096412 pmcpmc8796089 doi101177 20552173211072274,0.0
smouldering multiple sclerosis #39 real ms#39 ther adv neurol disord 2022 jan 25 1517562864211066751 doi 101177 17562864211066751 ecollection 2022abstractusing philosophical approach deductive reasoning challenge dominant clinicoradiological worldview defines multiple sclerosis ms focal inflammatory disease central nervous system cns provide range evidence argue real ms fact driven primarily smouldering pathological disease process natural history studies clinical trials relapses focal activity revealed magnetic resonance imaging mri ms patients placebo diseasemodifying therapies dmts found poor predictors longterm disease evolution dissociated disability outcomes addition progressive accumulation disability ms can occur independently relapse activity early disease course scenario underpinned diffuse smouldering pathological process may affect entire cns many putative pathological drivers smouldering ms can potentially modified specific therapeutic strategies approach may major implications management ms patients hypothesise therapeutically targeting state evident inflammatory disease activity neida sufficiently prevent disability accumulation ms meaning treatment also focus brain spinal cord pathological processes contributing slow loss neurological function also complemented holistic approach management systemic disease processes shown worsen ms outcomespmid35096143 pmcpmc8793117 doi101177 17562864211066751,0.0
rpp25 prognosticrelated biomarker correlates tumor metabolism glioblastoma front oncol 2022 jan 12 11714904 doi 103389 fonc2021714904 ecollection 2021abstractrpp25 25 kda protein subunit ribonuclease p rnase p proteincoding gene disorders associated rpp25 include chromosome 15q24 deletion syndrome diffuse scleroderma systemic sclerosis can complicated malignancy however functional role rpp25 expression glioblastoma multiforme gbm unclear study comprehensive bioinformatics analysis used evaluate impact rpp25 gbm occurrence prognosis differential analysis multiple databases showed rpp25 commonly highly expressed multiple cancers lowly expressed gbm survival prognostic results showed rpp25 prognostically relevant six tumors cesc gbm laml luad skcm uvm high rpp25 expression significantly associated poor patient prognosis except cesc analysis rpp25 expression gbm alone revealed rpp25 significantly downregulated gbm compared normal tissue receiver operating characteristic roc combined kaplanmeier km analysis cox regression analysis showed high rpp25 expression prognostic risk factor gbm predictive value 1year 2year 3year survival gbm patients addition expression rpp25 correlated level immune cell infiltration gene set enrichment analysis gsea results showed rpp25 mainly associated signalling pathways related tumor progression tumor metabolismpmid35096558 pmcpmc8790702 doi103389 fonc2021714904,0.0
optical coherence tomography optical coherence tomography angiography findings multiple sclerosis patients neuroophthalmology 2021 aug 20 46 1 1933 doi 101080 0165810720211963787 ecollection 2022abstractin addition ocular neurodegeneration multiple sclerosis ms accompanying microvascular changes retina thought occur study sought compare retinal neurodegenerative changes using optical coherence tomography oct microvascular changes using oct angiography octa ms patients healthy controls crosssectional study included 164 eyes 83 ms patients 114 eyes 57 healthy control subjects significant differences retinal nerve fibre layer rnfl ganglion cell complex gcc radial peripapillary capillary rpc vessel density vd ms group control group significant differences superficial capillary plexus scp vd deep capillary plexus dcp vd foveal avascular zone faz nonflow area nfa choriocapillary flow ccf values comparing eyes without previous optic neuritis showed significant differences oct octa measurements negative correlation found expanded disability status scale score disease duration rnfl gcc values positive correlation found rnfl gcc values scp vd rpc vd ms patients rpc vd values decreased correlation decreases rnfl gcc reduction increased disease duration disability criteria increased oct octa may important biomarkers mspmid35095132 pmcpmc8794252 doi101080 0165810720211963787,0.0
use diagnostic outcomes cancer patient pathways denmark place initial diagnostic workup important factor abstractintroductionthe cancer patient pathway nonspecific symptoms signs cancer nssccpp implemented denmark regional intraregional differences places initial diagnostic workup often including ct scan performed general practitioners gps others hospitals variations may influence use organ specific cancer patient pathways oscpps prognostic outcomes patients therefore aims 1 analyse ct scan referred gp hospital followed oscpps nssccpps national regional level 2 analyse nationally regionally diagnostic outcomes persons referred ct scan either gp hospital six months mortality one year ct scanmethodsa nationwide populationbased study including individuals first ct scan 20132016 either referred gp hospitalresultsoverall individuals ct scan referred gps likely start nssccpp oscpp individuals ct scan referred hospitals across five regions denmark ct scans referred gps associated reduced odds total mortality regions north or078 073 083 central or092 087 096 south or085 081 089 capital or096 091 100 zealand or085 079 090 increased odds cancerspecific mortality four regions ors ranging 115151 difference region north 100 091 110 conclusionno obvious association ct scans cpps reduced diagnoses mortality observed different diagnostic models might explain prognostic outcomes different use ct scans regions play large role differences incidence mortality,0.0
perceived stress multiple sclerosis patients relationship mood states pain experience abstractbackgroundmultiple sclerosis related stressors significant emotional impact patients multiple sclerosis likely experience disturbed mood states pain exacerbations experience stressful life eventsobjectivethe study aimed determine relationship increased perceived stress mood states pain experience patients multiple sclerosismethodsa convenience sample 110 patients multiple sclerosis assembled neuropsychiatric outpatient clinics el hadara orthopedic traumatology alexandria university hospital four tools used biosociodemographic data structured questionnaire perceived stress scale profile mood states numeric rating pain scaleconclusionthis study concluded majority patients studied experienced moderate severe levels increased perceived stress disturbed mood states pain perception found significantly associated patientsnull perceived stress levels,0.0
impact cara mandates nurse practitioner controlled substance prescribing oregon cohort study background 2017 united states comprehensive addiction recovery act cara expanded authorization prescribe buprenorphine opioid use disorder oud nurse practitioners nps compared physicians nps required complete 16 additional hours training controlled substance prescribing buprenorphine waiver application differential additional education mandate seen potential barrier evaluated impact requirement np waiver acquisition prescribing controlled substances comparing nps obtained waivers notmethodsthrough 20162018 oregon prescription drug monitoring program linked np licensure data identified factors associated waiver acquisition baseline 2016 evaluated changes controlled substance prescribing 2016 waiver acquisition 2018 using chisquare mannwhitney u testing calculated described controlled substance prescribing types rates patient level quantities including coprescribing benzodiazepines opioids nps multivariable linear regression compared prescribing waivered nonwaivered nps significant changes nonbuprenorphine controlled substance prescribingresultswaivered nps likely psychiatric certification prior disciplinary action generally higher levels nonbuprenorphine controlled substance prescribing nonwaivered counterparts significant increase opioid prescriptions per patient among waivered nps following cara implementation coprescribing benzodiazepines opioids significantly declined among waivered nps relative nonwaivered npsconclusionsalthough educational requirements rescinded 2021 applicants enhanced opioid prescribing training incorporated professional educational offerings regardless regulatory mandate recommended continued focus education regarding avoidance high risk prescribing coprescribing opioids benzodiazepines nps acquire waivers may take higher risk patients already using opioids findings may represent transitions practice patient setting,0.0
mind diet adherence might associated reduced odds multiple sclerosis results casecontrol study neurol ther 2022 jan 29 doi 101007 s4012002200325z online ahead printabstractintroduction mediterranean dietary approaches stop hypertension dash intervention neurodegenerative delay mind diet shown beneficial neuroprotective effects purpose research evaluate link mind diet adherence multiple sclerosis ms degenerative neurological illnessmethods hospitalbased casecontrol setting 77 patients relapsingremitting multiple sclerosis rrms 148 healthy individuals recruited validated 168item semiquantitative food frequency questionnaire used assess participants dietary intakes mind diet score logistic regression model used evaluate association mind diet adherence msresults significant difference rrms control groups median q1q3 age years p value 0001 body mass index bmi kg m2 p value 0001 total intake calories kcal p value 0032 carbohydrates g p value 0003 animalbased protein g p value 0009 fiber g p value 0001 adherence mind diet associated reduced odds ms adjusted odds ratio aor 010 95 percent confidence interval 95 ci 001088 p trend 0001 ms odds significantly lower last tertile green leafy vegetables aor 002 95 ci 000021 p value 0001 vegetables aor 017 95 ci 004073 p value 0001 butter stick margarine aor 020 95 ci 006065 p value 0008 beans aor 005 95 ci 001028 p value 0001 consumption significantly higher last tertile cheese aor 445 95 ci 170116 p value 0003 poultry aor 395 95 ci 101155 p value 0039 pastries sweets aor 139 95 ci 3046418 p value 0001 fried fast foods aor 328 95 ci 5391993 p value 0001 conclusion mind diet components including green leafy vegetables vegetables beans seem decrease odds ms besides butter stick margarine mind diets unhealthy components seem protective effects pastries sweets cheese poultry fried fast foods inverse effectpmid35094301 doi101007 s4012002200325z,1.0
healthcare disruptions use telehealth services among persons multiple sclerosis covid19 pandemic arch phys med rehabil 2022 jan 27s00039993 22 001617 doi 101016 japmr202112028 online ahead printabstractobjective current study examined healthcare disruptions use telehealth services among persons multiple sclerosis pwms coronavirus disease 2019 covid19 pandemicdesign crosssectional surveysetting general communityparticipants seventy pwms 93 healthy controls hcs majority respondents united states us 88 interventions applicablemain outcome measure s rates healthcare disruptions eg missing canceling appointments experiencing delays telehealth use ms nonms medical care mental healthcareresults usmajority predominantly white high socioeconomic status sample 3850 pwms reported experiencing disruptions ms nonms medical care 2033 reported disruptions mental healthcare significantly lower observed among hcs compared hcs pwms likely utilize telehealth inperson services especially mental healthcare majority pwms hcs reported satisfied telehealth services individuals higher degrees functional limitation experienced healthcare disruptions likely utilize telehealth services individuals lower degrees functional limitationconclusions despite high healthcare disruption rates pwms frequently utilized highly satisfied telehealth services covid19 pandemic due physical limitations commonly observed ms population may preclude travel telehealth services continued even resolution pandemic order expand access reduce healthcare disparitiespmid35093328 doi101016 japmr202112028,0.0
telemedicine strategic intervention cognitive rehabilitation ms patients covid19 acta neurol belg 2022 jan 30 doi 101007 s13760022018757 online ahead printabstractthe recent covid19 pandemic taken lives nearly 52 million now definite treatment considering close contact primary mode transmission telemedicine emerged essential medical care platform virtual medical communications offered clinicians opportunity visit follow patients efficiently lockdown telemedicine improved multiple sclerosis ms patients health quality life pandemic also used costeffective platform physical cognitive ms rehabilitation programs cognitive impairment common problem among ms patients even initial phases disease rehabilitation training programs rehacom brainhq speed processing training pst cognitrack made great strides improving wide range cognitive functions ms patients challenged regarding impact covid19 cognitive aspects ms patients efforts implement rehabilitation training applications increased webbased mobile applications virtual visits telephone followups examples efforts said limitations privacy socioeconomic disparities ehealth literacy study settings challenges neurologic examinationss raised since ms patients young beneficiaries encouraged embrace research field pave road feasible efficient ways cognitive enhancement ms patientspmid35094365 doi101007 s13760022018757,0.0
abnormal multisensory integration relapsingremitting multiple sclerosis exp brain res 2022 jan 30 doi 101007 s00221022063100 online ahead printabstracttemporal binding window tbw represents reliable index efficient multisensory integration process allows individuals infer sensory inputs different modalities pertain event tbw alterations reported neurological neuropsychiatric disorders seem negatively affects cognition behavior far still unknown whether deficits multisensory integration indexed abnormal tbw present even multiple sclerosis addressed issue testing 25 participants affected relapsingremitting multiple sclerosis rrms 30 agematched healthy controls participants completed simultaneity judgment task sj2 assess audiovisual tbw two unimodal sj2 versions used control tasks individuals rrms showed enlarged audiovisual tbw width range 166 ms + 198 ms compared healthy controls width range 177 + 66 ms thus showing increased tendency integrate temporally asynchronous visual auditory stimuli instead simultaneity perception unimodal visual auditory events overall differ controls results provide first evidence selective deficit multisensory integration individuals affected rrms besides wellknown motor cognitive impairments reduced multisensory temporal acuity likely caused disruption neural interplay different sensory systems caused multiple sclerosispmid35094114 doi101007 s00221022063100,0.0
2chlorodeoxyadenosine cladribine preferentially inhibits biological activity microglial cells int immunopharmacol 2022 jan 27 105108571 doi 101016 jintimp2022108571 online ahead printabstractcladribine 2cda synthetic chlorinated purine nucleoside analogue acts prodrug requiring intracellular phosphorylation activated biologically active selected cell types results reduction circulating t b lymphocytes implicated multiple sclerosis ms pathogenesis addition 2cda shows good central nervous system cns penetration can therefore exert action microglia astrocytes therefore studied effects 2cda microglial cells astrocytes emerging potential targets ms therapy effects peripheral immune system 2cda induced apoptosis microglial cells inhibited proliferation reduced production cytokines particularly proinflammatory cytokines il1 il6 tnf represent additional mechanisms 2cda may contribute limiting inflammatory pathways contrast astrocytes showed resistance action 2cda may explained differences intracellular phosphorylation insights mechanism action resistance 2cda cnsresident cells may prove crucial optimal usepmid35093689 doi101016 jintimp2022108571,0.0
metabolomics lipidomics approaches human tears systematic review surv ophthalmol 2022 jan 27s00396257 22 00008x doi 101016 jsurvophthal202201010 online ahead printabstractthe human tear film interface ocular surface external environment although investigation hindered small volume improvements preanalytical analytical methods allowed omics approach represent innovative biomarker search strategy still significant lack standardization representing barrier performing betweenstudies comparisons transferring experimental findings clinical use trials summarize preanalytical analytical procedures describe biomarkers can found using metabolipidomics approach provide expert opinion omics investigations human tears systematic review 38 studies searched pubmed combining boolean operators following keywords tear metabolomic lipidomic omics human tear metabolipidome wellcharacterized normal individuals using highresolution liquid chromatography coupled mass spectrometry lipid metabolite profiles influenced ocular eg dry eye disorders meibomian gland dysfunction contact lens wear glaucoma keratoconus pterygium systemic conditions eg multiple sclerosis investigating tear metabolipidome improve understanding pathogenesis ocular systemic diseases also provide diagnostic well prognostic biomarkerspmid35093405 doi101016 jsurvophthal202201010,0.0
mortality parkinson#39 s disease italy 1980 2015 neurol sci 2022 jan 30 doi 101007 s10072021058543 online ahead printabstractobjective evaluate mortality parkinsons disease pd italy long time period 19802015 discuss role possible general specific influencing factorsmethods based mortality data provided italian national institute statistics sex agespecific crude mortality rates computed whole country main geographical subareas rates standardized using direct annual mortality rates amrs indirect standardized mortality rates smrs methods smrs used evaluate geographical differences whereas amrs joinpoint linear regression analysis study mortality trendsresults considering entire period highest mortality rates observed males amr 100 000 90 males 525 females northwest central italy smr 100 overall pd mortality decreased mideighties onwards rapidly reversed trend period 19982002 rising maximum 2015 differences according sex geographical areasconclusions several factors may contributed rapid inversion decreasing trend mortality observed last part xx century possible explanations rising trend related increasing burden pd especially males certain italian regions caused different factors population aging physiological prevalence rise due incidence exceeding mortality growing exposure environmental occupational risk factors addition accuracy death certificate compilation account geographical differences temporal trend role levodopa recently introduced dopaminergic drugs also discussedpmid35094172 doi101007 s10072021058543,0.0
stereotyped bcell responses linked igg constant region polymorphisms multiple sclerosis eur j immunol 2022 jan 29 doi 101002 eji202149576 online ahead printabstractclonally related b cells infiltrate brain meninges cerebrospinal fluid multiple sclerosis ms patients mechanisms driving bcell response shaping immunoglobulin repertoires remain unclear used singlecell fulllength rnaseq bcell receptor reconstruction simultaneously assess phenotypes isotypes constant region polymorphisms paired heavy lightchain repertoires intrathecal b cells detected extensive clonal connections memory b cell antibodysecreting cell compartments observed clonally related cells different isotypes including igm igg1 igg1 iga1 igg1 igg2 igm iga1 strong dominance g1m1 allotype constant region polymorphisms antibodysecreting cells memory b cells tightly linked g1m1 allotype found preferential pairing immunoglobulin heavychain variable ighv 4 gene family variable igkv 1 gene family ighv439 gene used showed highest frequency pairing igkv15 igkv1 d 33 results link igg constant region polymorphisms stereotyped bcell responses ms indicate intrathecal bcell response patients directed structurally similar epitopes article protected copyright rights reservedpmid35094395 doi101002 eji202149576,0.0
validity reliability tampa kinesiophobiafatigue scale patients multiple sclerosis ir j med sci 2022 jan 30 doi 101007 s1184502102902x online ahead printabstractbackground kinesiophobia can barrier physical activity patients multiple sclerosis pwms can develop result fear avoidance reactions due fatigue however valid reliable scale available assess kinesiophobia due fatigue pwmsaims investigate testretest reliability construct validity tampa scale kinesiophobiafatigue tskf pwmsmethods eightyseven pwms included study addition tskf following measurements used construct validity expanded disability status scale edss fatigue severity scale fss fatigue impact scale fis 6minute walking test 6mwt international physical activity questionnaire ipaq beck depression inventory bdi multiple sclerosis quality life scale54 msqol54 tskf administered twice 37 days apart measure testretest reliabilityresults intraclass correlation coefficient tskf 0867 weak correlation ipaq edss moderate correlation msqol54 6mwt strong correlation bdi fss fis respectively rho 0345 rho 0365 rho 0544 rho 0449 rho 0690 rho 0602 rho 0650 scale good performance discriminate disease severity area curve auc value 0730conclusions tskf excellent reliability moderatetogood validity evaluating kinesiophobia scale may useful outcome measurement assessment kinesiophobia due fatigue pwmspmid35094232 doi101007 s1184502102902x,0.0
deep learning approach predicting disease progression multiple sclerosis using magnetic resonance imaging invest radiol 2022 jan 28 doi 101097 rli0000000000000854 online ahead printabstractobjectives magnetic resonance imaging mri important tool diagnosis monitoring disease course multiple sclerosis ms however prognostic value predicting disease worsening still debated aim study propose deep learning algorithm predict disease worsening 2 years followup multicenter cohort ms patients collected italian neuroimaging network initiative using baseline mri compare 2 expert physiciansmaterials methods 373 ms patients baseline t2weighted t1weighted brain mri scans well baseline 2year clinical cognitive assessments collected italian neuroimaging network initiative repository deep learning architecture based convolutional neural networks implemented predict 1 clinical worsening expanded disability status scale edss based model 2 cognitive deterioration symbol digit modalities test sdmt based model 3 edss + sdmtbased model method tested independent data set compared performance 2 expert physiciansresults test set convolutional neural network model showed high predictive accuracy clinical 833 cognitive 677 worsening although highest accuracy reached training algorithm using edss sdmt information 857 artificial intelligence classification performance exceeded 2 expert physicians 70 accuracy human raters conclusions developed robust accurate model predicting clinical cognitive worsening ms patients 2 years based conventional t2weighted t1weighted brain mri scans obtained baseline algorithm may valuable supporting physicians clinical practice earlier identification ms patients risk disease worseningpmid35093968 doi101097 rli0000000000000854,0.0
global dna methylation changes treated untreated ms patients measured time j neuroimmunol 2022 jan 7 364577808 doi 101016 jjneuroim2022577808 online ahead printabstractmultiple sclerosis ms autoimmune neurological disease investigated genomewide dna methylation profiles cd4+ cd8+ t cells ms patients healthy controls baseline followup visit patients treatmentnave baseline either treatment remained untreated followup visit ms patients show changes t cell dna methylation profiles compared healthy controls time pronounced differences observed untreated ms patients findings underline potential dna methylation biomarkers mspmid35093762 doi101016 jjneuroim2022577808,0.0
identification mirnas potential effects multiple sclerosis related pathways using silico analysis abstractbackground micrornas mirnas regulate gene expression posttranscriptionally via mrna degradation result impact variety pathways organisms important health disease mirnas can used potential diagnostic prognostic therapeutic biomarkers immune nervous systemrelated diseases msmethod differentially expressed mirnas peripheral blood samples patient control groups selected ncbi geo datasets using geo2r common mirnas related pathways analyzed using mirnet mirwalk diana mirpath kegg pathway target genes proteinprotein interactions also evaluated using string genemaniaresults found 12 common mirnas four determined important msrelated pathways immune neural signaling networks include pathways neurotrophin jakstat b cell receptor erbb mapk fc gamma rmediated phagocytosis chemokine t cell receptor signalling pathways moreover target gene analyses performed mapk1 pik3cd pik3r1 pik3r2 pik3r3 pik3r5 akt2 sos2 raf1 genes found analysis showed identified genes related pathways interactions multiple points overlapping points commonly found pi3kakt signaling pathway conclusion paper msrelated mirnas potential effects related pathways evaluated study can used understanding ms pathogenesis provides new tools discovery new therapies,0.0
multiple sclerosis performance test mspt normative study 428 healthy participants ages 18 89 abstractbackgroundthe multiple sclerosis performance test mspt selfadministered ipadbased computerized system quantifying neuroperformance cognition upper lower extremity motor function vision patients multiple sclerosis ms objectivethe goal study provide regressionbased norms four mspt test modules adjust influence demographic variables age education sex methodsthe mspt administered 428 cognitively intact healthy adults ages 18 89 years participants recruited achieve demographically stratified sample four geographically diverse united states testing sitesresultsthe amount shared variance test performance accounted demographic variables 1823 upper extremity motor test 31 walking speed test 32 low contrast visual acuity test 48 cognitive test four test modules significantly influenced age linear nonlinear effects education additionally sex influenced performance cognitive walking speed testsconclusionthis study provides regressionbased equations can enhance clinical interpretation mspt scores adjusting potential influences age education sex,0.0
comorbidity multiple sclerosis emphasis patientreported outcomes abstractbackground aim study estimate prevalence comorbid conditions adverse health behaviors relapsingremitting multiple sclerosis rrms patients evaluate association comorbidity ms outcomes relapse rate fatigue quality life lithuanian settingmethods prospective cohort study carried ms center lithuanian university health sciences hospital kaunas clinics november 2016 march 2021 people ms filled selfreport comorbidity adverse health behavior questionnaire visual analogue fatigue scale vafs short form 36 sf36 v2 health related quality life questionnaire qol information disability relapses acquired medical documentation lithuanian ms registry baseline 24month observational period chi square ttest anova mannwhitney u used basic statistical evaluation multivariable logistic regression models used prognose ms outcomes association comorbidity adverse health behaviors adjusting age baseline disabilityresults 230 rrms patients 167 726 women average age 42 years 207 persons followed observational period included relapse analysis 112 487 participants reported least one comorbidity prevalent arterial hypertension 191 depression 165 anxiety 148 people comorbidities higher fatigue 66 vs 53 p0001 lower quality life overall sf36 463 vs 591 p0001 people consuming alcohol fewer relapses per 24 months 056 vs 082 p001 lower fatigue 57 vs 64 p003 better quality life overall sf36 568 vs 456 p0001 compared abstinentsin regression models comorbidities associated severe 7 vafs fatigue exp b 198 95 ci 102 386 p0043 diminished 50 sf36 qol exp b 350 95 ci 172 709 p0001 depression independently associated lower qol exp b 286 95 ci 104 788 p0042 severe fatigue exp b 465 95 ci 239 901 p0001 anxiety diminished qol exp b 499 95ci 167 1492 p0002 light alcohol consumption compared abstinents associated decreased risk relapse 24 months exp b 044 95 ci 024 077 p0005 severe fatigue exp b 048 95 ci 024 098 p0042 lower qol exp b 032 95 ci 016 065 p0002 conclusion comorbidity relevant issue multiple sclerosis half people ms report concomitant conditions hypertension depression anxiety especially prevalent ms study comorbidity associated quality life fatigue relapse rate depression anxiety independently associated lower quality life higher fatigue light alcohol consumption associated reduced relapse risk less fatigue better quality life overweight tobacco smoking seem negative impact ms outcomes sample,0.0
variability objective gait measures across expanded disability status scale people living multiple sclerosis crosssectional retrospective analysis abstractbackground expanded disability status scale edss widely utilized clinical trials routine care evaluate disease burden progression among people multiple sclerosis pwms however instrumental gait measures may suitable edss track walking disability pwms crosssectional study aimed quantify variability spatiotemporal gait measures within homologous edss categoriesmethods total 205 pwms age465 sd105 years 722 female edss range1065 studied retrospective analysis participants underwent walking assessments gaitrite system following spatiotemporal gait measures recorded gait speed mean normalized velocity mnv base support stride length step length percentage gait cycle spent double support single support functional ambulation profile edss evaluated certified neurologistresults gait measures exhibited fair strong correlations scores edss 081s025 poor fair correlations disease duration 032s017 overall percent variability gait measures increased across edss categories coefficients variation ranging 69 372 minimal disability group edss25 81 334 223 538 moderate 2545 disability groups respectivelyconclusion spatiotemporal gait measures great variability within homologous edss categories high percent variability gait speed mnv 50 suggests walking ability varies substantially within across disability levels therefore addition edss comprehensive multidimensional objective patientcentric metrics needed accurately evaluate disability pwms,0.0
healthrelated quality life neuromyelitis optica spectrum disorder patients argentinean cohort abstractbackground aimed describe healthrelated quality life hrqol patients neuromyelitis optica spectrum disorders nmosd compare hrqol nmosd patients multiple sclerosis ms healthy controls hc study associations hrqol clinical variables diseasemethods crosssectional study carried patients nmosd seropositive ms hc enrolled agematched hrqol studied using argentinean validation sf36 health questionnaire demographic clinical characteristics analyzed well edss total scores subscales sf36results 243 individuals included nmosd 53 ms100 hc90 mean edss 306 201 nmosd 267 183 ms mean disease duration 62 44 63 53 years respectively significant statistical differences observed total sf36 score nmosd ms vs hc p 001 differences found total sf36 score compared nmosd vs ms overall nmosd patients scored significantly lower total sf36 subscale scores compared hc p 005 nmosd patients also showed significant differences bodily pain 588 298 vs 751 251 p 001 general health 444 209 vs319 231 p 001 compared ms differences found comparing rest subscales found higher edss scores 128 p003 disease duration 08 p002 significantly associated lower worse general health dependent variable score nmosd patients applied multiple linear regression analysis additionally observed higher edss scores 102 p0008 presence relapses previous year 289 p002 significantly associated lower worse physical functioning dependent variable scoreconclusion pain seems significant undertreated symptom nmosd patients strongly impact hrqol patientreported hrqol scales scores provide comprehensive additional prognostic information beyond physical disability score,0.0
practical issues concerning use magnetic resonance imaging multiple sclerosis latin america discussion 16 centres behalf foro latam em study group abstractmagnimscmscnaims consensus recommendations use mri patients multiple sclerosis recently published fundamental improving patient care implementation previous magnims recommendations established many countries addressing local limitations behind difficulties needed panel 14 ms neurologists 16 different reference centres chile argentina mexico colombia ecuador panam per brazil met discuss current situation regarding use mri ms including access availability b standardized acquisition protocols reports c multicentric research potential,0.0
improving mental health multiple sclerosis interpersonal emotion regulation intervention prospective randomized controlled trial abstractbackgroundover third people multiple sclerosis pwms struggle poor mental health exacerbates physical symptoms complicates clinical treatment address tested efficacy interpersonal emotion regulation intervention intervention seeks improve mental health teaching participants use emotion regulation strategies leverage social support eg reaching others comfort experiencing stressful event methodnineteen pwms completed prospective blinded randomized controlled trial intervention n10 control n9 intervention participants met interventionist six weeks discuss emotional challenges develop goals use interpersonal emotion regulation strategies participants control condition met interventionist schedule emotion regulation strategies measured manipulated preregistered primary outcomes selfreported depression stress quality life qol preregistered secondary outcome selfreported social supportresultsintervention participantsnull depression scores improved time 1 time 2 mean difference360 95 ci 044676 yet remained unchanged control group mean difference167 95 ci 500167 overall interaction f 1 17 584 p027 p2256 remaining primary stress qol secondary social support outcomes show significant effect intervention stress p601 p2016 qol p179 p2104 social support p140 p2124 conclusioninterpersonal emotion regulation beneficial improving depression pwms consequently strategies can implemented conjunction existing mental health treatments holistic approach improving wellbeing,0.0
using myelin water imaging link underlying pathology clinical function multiple sclerosis scoping review abstractbackgroundmultiple sclerosis ms symptoms pathology heterogenous complex identifying links msrelated pathology ie myelin damage associated clinical symptoms critical developing targeted therapeutics conventional mri commonly used ms diagnosis disease monitoring lacks specificity functional performance myelin water imaging mwi demonstrates increased specificity myelin viewed gold standard imaging myelin content vivo yet paucity mwi studies ms limited number also examine clinical function thus remains unknown whether mwi corresponds functional performance ms scoping review aimed examine relations mwi functional domains relevant ms inform guide future researchmethodsseven databases searched inception september 1 2021 studies adults ms included brain mwi either measure physical function measure cognitive function measure disease severity included thirteen studies 11 observational 2 intervention met inclusion criteriaresultsthe commonly investigated mwi metric myelin water fraction mwf persons ms demonstrated markedly decreased mwf compared healthy controls globally across brain regions interest rois decreased mwf associated higher disability worse motor cognitive performance decreased intervention response five studies examined structurefunction relationships brain areas related walking cognitive function six studies extracted mwi metrics explicit brain roisconclusionsmwi neuroimaging technique increased specificity myelin offers greater insight msdriven pathology clinical manifestations including motor cognitive dysfunction rehabilitation response scoping review identified critical gaps mwi research ms offer future perspectives including roibased studies inclusion multidomain functional assessment examining mwi provide evidence neuroplasticity following training,1.0
multilocus evaluation genetic predictors multiple sclerosis gene 2021 oct 14146008 doi 101016 jgene2021146008 online ahead printabstractbackground genomewide association studies identified numerous susceptibility loci multiple sclerosis populations european ancestry associations always reproducible populations due admixture different linkage disequilibrium patterns obscuring true association signalsobjective aim identify genetic predictors multiple sclerosis three ethnically homogenous populations volgaural region russian federationmethods largest date study multiple sclerosis russian population involving 2048 participants republic bashkortostan russian federation 641 patients multiple sclerosis 1407 unaffected individuals performed replication analysis previously identified genomewide signals multiple sclerosis associations tested using logistic regression analysis additive genetic model adjusted sex metaanalysis study results three populations performed fixed effects random effects modelsresults demonstrate association multiple sclerosis five variants inava rs7522462 eomes rs11129295 c6orf10 rs3129934 cd86 rs9282641 gpr65 rs2119704 strongest association or216 ci185274 p253x1013 detected rs3129934 polymorphism major histocompatibility region multilocus analysis revealed 322 27 allelic patterns associated multiple sclerosis men women respectively women highest risk ms conferred c6orf10 rs3129934t t + stat3 rs744166t combination or1187 men c6orf10 rs3129934t + eomes rs11129295c + rps6kb1 rs180515c combination or325 conclusion confirm five associations multiple sclerosis previously reported genomewide scans europeans three ethnic groups volgaural region russiapmid34656742 doi101016 jgene2021146008,0.0
kappa free light chains diagnostic performance multiple sclerosis utility clinical laboratory clin chim acta 2022 jan 26s00098981 22 000262 doi 101016 jcca202201017 online ahead printabstractbackground automated technically simple analytical methods offering objective results highly valued clinical laboratories kappa free light chains kflc cerebrospinal fluid csf promising multiple sclerosis ms biomarkers particularly kappa k indexmethods kflc determined csf serum samples patients diagnosed ms clinically radiologically isolated syndrome n 39 controls n 152 inflammatory noninflammatory neurological disorders diagnostic performance several kflc parameters previously determined oligoclonal band ocb testing igg index assessed k index decision threshold sample screening identified reduction performed ocb analyses estimated accordinglyresults higher kflc parameters detected ms group k index performed best among auc 092 725 cutoff showed better sensitivity 85 vs 77 though less specificity 88 vs 91 ocbs comparatively igg indexs performance inferior auc 083 decision k index threshold 255 97 sensitivity reduce ocb testing 52 studied populationconclusions proposed 725 cutoff assist ms diagnostics identify false negative cases ocb studies sequential algorithms using k index decision perform ocb detection improve laboratory efficiency substantially reduce costspmid35092724 doi101016 jcca202201017,0.0
abnormal oxidative metabolism cuprizone mouse model demyelination vivo nirsmri study neuroimage 2022 jan 25118935 doi 101016 jneuroimage2022118935 online ahead printabstractdisruptions oxidative metabolism may occur multiple sclerosis demyelinating neurological diseases impact demyelination metabolic rate also understood possible mitochondrial damage may associated many neurological disorders study oxidative metabolism one model demyelination implemented novel multimodal imaging technique combining nearinfrared spectroscopy nirs mri cuprizone mouse model cuprizone model used study demyelination may associated inhibition mitochondrial function cuprizone mice showed reduced oxygen extraction fraction 391 p0001 increased tissue oxygenation 64 p0001 reduced cerebral metabolic rate oxygen cortical gray matter 621 p0001 changes resolved cessation cuprizone exposure partial remyelination decrease hemoglobin concentration 344 p0001 change cerebral blood flow also observed demyelination oxidized state mitochondrial enzyme cytochrome c oxidase cco increased 463 p0001 reduced state decreased 344 p005 significantly cuprizone mice total amount cco change significantly cuprizone exposure total cco decline recovery control 231 p001 cuprizone 288 p0001 groups may relate age reduction magnetization transfer ratio indicating demyelination found cuprizone group cerebral cortex 32 p001 corpus callosum 55 p0001 summary able detect evidence altered cco metabolism cuprizone exposure consistent mitochondrial defect observed increased oxygenation reduced metabolic rate associated reduced myelination gray white matter novel multimodal imaging technique applied shows promise noninvasively assessing parameters associated oxidative metabolism mouse models neurological disease translation study oxidative metabolism human brainpmid35091079 doi101016 jneuroimage2022118935,1.0
cortical subcortical dysmetabolism dynamic markers clinical disability course antilgi1 encephalitis neurol neuroimmunol neuroinflamm 2022 jan 28 9 2 e1136 doi 101212 nxi0000000000001136 print 2022 marabstractbackground objectives 18f fluorodeoxyglucose fdg pet study evaluates accuracy semiquantitative measurement putaminal hypermetabolism identifying antileucinerich gliomainactivated1 lgi1 protein autoimmune encephalitis ae addition extent brain dysmetabolism association clinical outcomes longitudinal metabolic changes immunotherapy lgi1ae examinedmethods fdgpet scans 49 agematched sexmatched subjects 13 lgi1ae group 15 nonlgi1ae group 11 alzheimer disease ad 10 negative controls ncs followup scans 8 patients lgi1 ae median 6 months immunotherapy analyzed putaminal standardized uptake value ratios suvrs normalized global brain psuvrg thalamus p th midbrain p mi evaluated diagnostic accuracy suvrg applied analysesresults psuvrg p th p mi higher lgi1ae group nonlgi1ae group ad group ncs p 005 p mi psuvrg differentiated lgi1ae group robustly groups areas curve 084099 mediotemporal lobe mtl suvrg increased lgi1ae nonlgi1ae groups compared ncs p 005 suvrg decreased several frontoparietal regions increased pallidum caudate pons olfactory inferior occipital gyrus lgi1ae group compared ncs p 005 lgi1ae group mtl putaminal hypermetabolism reduced immunotherapy normalization regional cortical dysmetabolism associated clinical improvement 6 20month followupdiscussion semiquantitative measurement putaminal hypermetabolism fdgpet may used distinguish lgi1ae pathologies metabolic abnormalities lgi1ae extend beyond putamen mtl subcortical cortical regions fdgpet may used evaluating disease evolution lgi1aeclassification evidence study provides class ii evidence semiquantitative measures putaminal metabolism pet can differentiate patients lgi1ae patients without lgi1ae patients ad ncspmid35091466 doi101212 nxi0000000000001136,0.0
subsecond accurate myelin water fraction reconstruction fastt2 data 3d unet magn reson med 2022 jan 28 doi 101002 mrm29176 online ahead printabstractpurpose develop 3d unet convolutional neural network rapid extraction myelin water fraction mwf maps sixecho fast acquisition spiral trajectory t2 prep data evaluate accuracy comparison multilayer perceptron mlp networkmethods mwf maps extracted 138 patients multiple sclerosis using iterative threepool nonlinear leastsquares algorithm nlls without spatial regularization srnlls used groundtruth labels train validate test unet mlp networks means accelerate data fitting network testing performed 63 patients multiple sclerosis numerically simulated brain phantom snr 200 100 50results simulations showed unet reduced mwf mean absolute error 301 564 168 536 whole brain 412 544 214 494 lesions predicting srnlls nlls mwf respectively compared mlp better performance lower snrs unet also outperformed mlp predicting srnlls mwf vivo multiplesclerosis brain data reducing mean absolute error whole brain 619 lesions 675 however mlp yielded 411 517 lower mean absolute error predicting vivo nlls mwf whole brain lesions respectively compared unet wholebrain mwf processing time using gpu 064 seconds unet 074 seconds mlpconclusion subsecond wholebrain mwf extraction fast acquisition spiral trajectory t2 prep data using unet feasible provides better accuracy mlp predicting mwf output srnlls algorithmpmid35092094 doi101002 mrm29176,1.0
covid19 vaccination patients multiple sclerosis safety humoral efficacy third booster dose j neurol sci 2022 jan 21 434120155 doi 101016 jjns2022120155 online ahead printabstractbackground immunity sarscov2 wanes following first second doses vaccination third dose administered several countries around world similarly first doses risks related vaccination humoral immune response patients multiple sclerosis ms need assessedobjective characterize safety humoral immune response following third dose covid19 vaccination large cohort ms patientsmethods assessed safety third dose bnt162b2covid19 mrna vaccination adult ms patients evaluated sarscov2 igg responseresults two hundred eleven adult ms patients received third dose bnt162b2 covid19 vaccination median follow time 66 days vaccine administration iqr 5484 frequency adverse event 545 common reported adverse events fatigue local pain injection site fever muscle joint pain transient increase ms symptoms reported 38 patients none requiring treatment rate acute relapses treated iv steroids 33 subgroup 55 patients 20 untreated 35 treated vaccinationsafe diseasemodifying treatments sarscov2 igg levels increased 21fold median sd 216 5305 conclusions third dose covid19bnt162b2 vaccine proved safe ms patients increased risk relapse activity untreated patients patients treated vaccinationsafe diseasemodifying treatments show significant increase sarscov2 igg levels following third dose vaccinationpmid35091386 doi101016 jjns2022120155,0.0
optic nerve lesion length acute phase optic neuritis predictive retinal neuronal loss neurol neuroimmunol neuroinflamm 2022 jan 28 9 2 e1135 doi 101212 nxi0000000000001135 print 2022 marabstractbackground objectives acute optic neuritis classical presenting symptom multiple sclerosis ms neuromyelitis optica spectrum disorders nmosd antimogassociated disorders resulting visual impairment variable can severe clinicians need predictive biomarkers optimize management acute longitudinal study irmano nct03651662 evaluated ability optic nerve lesion length measured mri acute phase predict retinal neuroaxonal loss visual impairment chronic stagemethods conducted longitudinal study irmano nct03651662 patients presented clinical episode 8 weeks patients underwent retinal optical coherence tomography oct brain optic nerve mri including 3d doubleinversion recovery dir sequence acute phase 12 months later primary outcomes optic nerve dir hypersignal lesion length macular ganglion cellinner plexiform layer gcipl volume measured oct lowcontrast monocular visual acuity lcmva results study group included 51 patients 33 women mean age 324 years 79 recruited patients clinically isolated syndrome n 20 relapsingremitting ms n 23 isolated n 6 first clinical episode nmosd n 2 optic nerve dir hypersignal observed 1 symptomatic optic nerves inclusion mean optic nerve lesion length mm 1235 598 mean gcipl volume mm3 significantly decreased inclusion 190 018 m12 167 021 p 00001 optic nerve lesion length inclusion significantly associated gcipl thinning estimate sd 0012 0004 p 00016 lcmva m12 0016 0003 p 0001 optic nerve lesion length significantly increased m12 1576 870 p 00007 increase optic nerve lesion length significantly associated gcipl thinning inclusion m12 0012 0003 p 00011 discussion acute phase optic nerve lesion length imaging biomarker predictive retinal neuroaxonal loss chronic visual impairment can help stratify future therapeutic strategies acute onclassification evidence study provides class evidence optic nerve lesion length measured mri acute phase first episode associated longterm retinal neuroaxonal loss visual impairmentpmid35091465 doi101212 nxi0000000000001135,0.0
pterostilbene protects optic nerves retina murine model experimental autoimmune encephalomyelitis via activation sirt1 signaling neuroscience 2022 jan 25s03064522 22 000306 doi 101016 jneuroscience202201016 online ahead printabstractoptic neuritis retinal damage common manifestations multiple sclerosis ms pterostilbene pt used treat multiple diseases antiinflammatory antiapoptosis neuroprotective activities study aimed investigate whether pt exerts therapeutic effect optic neuritis retinal damage triggered ms experimental autoimmune encephalomyelitis eae experimental model ms induced female c57bl 6 mice immunizing mog3555 peptide treating pertussis toxin mice intraperitoneally injected 20 mg kg 40 mg kg pt daily 25 days 24 h post immunization found pt alleviated eae severity delayed eae onset moreover pt mitigated eaeinduced optic nerves retinal inflammation indicated decreased iba1+ gfap+ cells mrna levels interleukin6 tumor necrosis factor interleukin1 increased iba1+sirtuin 1 sirt1 + gfap+sirt1+ cells optic nerves retina pt also protected optic nerves demyelination axonal loss retina disorders retinal morphology apoptosis retinal ganglion cells highdose pt significant effect protection optic nerves retina eae lowdose pt addition pt activated sirt1 signaling optic nerves retina notably ex527 inhibitor sirt1 reversed effect highdose pt optic nerves retina indicating pt exerted protective effect via activating sirt1 signaling study provides potential candidate treating mspmid35090883 doi101016 jneuroscience202201016,1.0
multiple sclerosis inflammatory bowel disease systematic review metaanalysis ann clin transl neurol 2022 jan 29 doi 101002 acn351495 online ahead printabstractbackground multiple sclerosis ms inflammatory bowel disease ibd two autoimmune diseases seriously affect patients quality life previous studies established association ms ibd including crohns disease cd ulcerative colitis uc results inconsistent aim study quantify prevalences association ms ibdmethods pubmed web science embase databases searched november 2020 studies reporting data ms among patients ibd vice versa main outcomes proportion ms patients ibd vice versa well association risk ratio rr ibd ms ms ibdresults based analysis 17 studies prevalence ms patients ibd 02 95 ci 0104 prevalence ibd patients ms 06 95 ci 0409 patients ms higher prevalence ibd controls rr 153 95 ci 138170 p 000001 similarly high risk developing cd rr 141 95 ci 114174 p 0001 uc rr 142 95 ci 117171 p 00003 patients ms p subgroup differences 097 patients ibd higher prevalence ms controls rr 191 95 ci 106345 p 003 conclusions clinicians aware increased risk ibd ms comorbidity diagnostic process systematic diagnosis management earlier stage suggestedpmid35092169 doi101002 acn351495,0.0
multiple sclerosis functional independence measure 107 best predictor outcome clean intermittent catheterization training ann phys rehabil med 2022 jan 25101636 doi 101016 jrehab2022101636 online ahead printabstractbackground assessment motor cognitive functions recommended clean intermittent catheterization training two validated instruments functional independence measure fim pencil paper test pptest associated ability learn selfcatheterization people multiple sclerosisobjectives aimed compare performance tools predicting outcome clean intermittent catheterization training multiple sclerosismethods people multiple sclerosis attending tertiary neurourology department 2011 2019 eligible clean intermittent catheterization included retrospective study reference standard ability perform least 2 trials selfcatheterization end training session 2 index tests fim pptest administered teaching session diagnostic performance estimated calculating sensitivity specificity area receiver operating characteristic curve auc auc values compared twosided delong testresults included 395 individuals mean sd age 498 12 years 70 women end session 87 patients succeeded learning selfcatheterization optimal cutoffs fim 107 pptest 13 estimated resulting sensitivity 73 95 confidence interval 6877 73 6777 specificity 73 5984 63 4976 respectively auc values fim pptest significantly different 079 vs 073 p0049 effect size large fim cohens d 114 pptest cohens d087 conclusions fim value 107 best specificity predict outcome clean intermittent catheterization training people multiple sclerosis sensitivity fim pptest similar large effect size outcome selfcatheterization training multiple sclerosispmid35091114 doi101016 jrehab2022101636,0.0
single nucleotide variants around connective tissue growth factor ctgf#x2f ccn2 gene association multiple sclerosis risk disability scores rate disease progression neurol sci 2022 jan 29 doi 101007 s10072021058525 online ahead printabstractbackground study aimed explore possible association single nucleotide polymorphisms snps upstream rs9402373 downstream regions rs9399005 rs12526196 gene encoding connective tissue growth factor ctgf ccn2 relapsingremitting multiple sclerosis rrms risk clinical parameters including disability scores rate disability progressionmaterials methods total 200 patients rrms 305 controls genotyped using realtime pcr rs1252696 c t rs9402373 g c pcrrflp rs9399005 c t methods furthermore association genotypes clinical parameters including expanded disability status scale edss score multiple sclerosis severity score msss age onset duration disease duration treatment presence contrastenhancing lesions analyzedresults rs9399005 genotypes tt ct dominant model significant predictors rrms vs control status logistic regression analysis 145 95 ci 101208 p 04 moreover genotypes rs9399005 associated msss 24 354 95 ci 156805 p 003 addition msss lower patients least one rs12526196c allele corresponding patients tt genotype p 02 conclusion knowledge first evidence involvement variants around ctgf gene ms risk disability progressionpmid35091888 doi101007 s10072021058525,0.0
association relapses stress depression people multiple sclerosis covid19 pandemic neurol sci 2022 jan 29 doi 101007 s1007202205917z online ahead printabstractbackground stress potential trigger clinical radiological activity multiple sclerosis ms covid19 pandemic relevant source mental distress people ms pwms deeply impacted disease managementobjective investigate association stress anxiety depression risk relapse covid19 pandemicmethods electronic database used clinical practice extracted data relapsingremitting rr relapsingprogressive rp ms patients calculated annualized relapse rate arr 2019 2020 01 12 2020 30 12 2020 enrolled patients invited fill google forms survey investigate depression anxiety stress posttraumatic stress disorder ptsd results selected 216 patients rr rpms calculate arr compared 2019 2020 significant increase arr p 00142 216 selected pwms 154 completed survey matching survey responses incidence relapses 2020 significant association relapses stress p 0030 relapses depression p 0011 relapses anxiety p 0130 ptsd p 0279 conclusions results support hypothesis pandemicrelated stress associated clinical exacerbations possible consequence covid19 impact ms carepmid35092543 doi101007 s1007202205917z,0.0
lifetime physical activity associated gut bacteria brain health people multiple sclerosis focus physical activity intensity abstractbackground physical activity can improve brain health people multiple sclerosis pwms one underlying mechanisms can modulation gut bacteria association different intensity physical activity lifetime brain volume lesion volume number gut bacteria counts investigated current studymethods fortyfive pwms recruited magnetic resonance imagining used evaluate brain volume lesion volume number also stool samples taken evaluation faecalibacterium prausnitzii akkermansia muciniphila prevotella bacteroidescount moreover lifetime physical activity assessed using adapted version historical activity questionnaireresults data revealed significant association physical activity brain volume r041 lesion volume r035 lesion number r037 akkermansia muciniphila r034 prevotella r052 bacteroides r032 count p005 moderateintensity physical activity associated brain volume r033 lesion volume r038 prevotella r035 bacteroides r040 count p005 moreover vigorousintensity physical activity associated brain volume r038 lesion number r039 akkermansia muciniphila r030 prevotella r056 count p005 conclusion results suggest lifetime physical activity associated brain health gut bacteria count pwms additionally heterogeneity association physical activity intensities studied variables indicates importance using different intensities physical activity greater benefit physical activity,0.0
human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing inhibitory role il16 myelination abstractone therapeutic approaches treatment autoimmune demyelinating disease multiple sclerosis ms bone marrow mesenchymal stromal cell hbmmscs transplantation however given capacity enhance myelination vitro hypothesised human olfactory mucosaderived mscs hommscs may possess additional properties suitable cns repair herein examined efficacy hommscs versus hbmmscs using experimental autoimmune encephalomyelitis eae model msc types ameliorated disease delivered initial onset symptomatic disease yet hommscs improved disease outcome administered established disease animals severe neurological deficits histological analysis spinal cord lesions revealed hommsc transplantation reduced bloodbrain barrier disruption inflammatory cell recruitment enhanced axonal survival early time points posthommsc treatment animals reduced levels circulating il16 reflected ability immune cells secrete il16 level il16 spinal cord inflammatory lesions vitro investigation revealed inhibitory role il16 oligodendrocyte differentiation myelination moreover availability bioactive il16 demyelination reduced presence hommscs combined data suggests human hommscs may therapeutic benefit treatment ms via il16mediated pathway especially administered active demyelination inflammation,1.0
functional performance patient satisfaction comparison 3d printed standard transradial prosthesis case report background delay amputation prosthesis fitting contributes high rate prosthetic abandonment despite advances technology threedimensional 3d printing allowed rapid fabrication prostheses allowing individuals amputations interact prosthesis shortly procedure may reduce rejection chances purpose current investigation compare functional outcomes patient satisfaction standard transradial prosthesis fitted clinic 3dprinted prosthesis fitted remotely standard prosthesis featured hook terminal device 3d printed prosthesis terminal device functional handresultsthe main finding case study use 3d printed arm prosthesis fitted remotely resulted better functional performance lower overall patient satisfaction standard arm prosthesis use 3d printed arm resulted improved gross manual dexterity measured box block test 3d printed prosthesis also allowed improved performance bimanual coordination however standardhook device scored higher patient satisfaction survey results patients concerns 3d printed prosthesis durability effectiveness deviceconclusionwhile durability complex grip patterns remain concern positive attributes 3d printed prostheses include visual appeal ease donning customization parameters improve upperlimb symmetry offers promising option familiarize new amputee patients use prosthesis rapid manufacturing remote fitting allows 3d printed devices serve postoperative transitional devices may function definitive devices minimal loss functionality standard clinicbased prostheses availablemethodsthe patient 59yearold male traumatic transradial amputation dominant arm 3d printed transradial prosthesis remotely fitted manufactured using photogrammetry assessments performed initially standardhook prosthesis 3d printed device 5week familiarization period functional outcomes evaluated using box block test bimanual coordination tray test patient satisfaction evaluated using two selfreported questionnaires quest 20 modified opus,0.0
fluoxetine inhibited activation a1 reactive astrocyte mouse model major depressive disorder astrocytic 5ht2br#x2f arrestin2 pathway background fluoxetine selective serotonin reuptake inhibitor reported directly bind 5ht2b receptor 5ht2br precise mechanisms whereby fluoxetine confers antidepressive actions via 5ht2br fully understood although neuroinflammationinduced a1 astrocytes involved neurodegenerative diseases role a1 astrocyte pathogenesis treatment major depressive disorder mdd remains unclearmethodsmice subjected chronic mild stress cms 6 weeks subsequently treated fluoxetine 4 weeks depressivelike anxietylike behaviors activation a1 reactive astrocyte hippocampus cortex mice measured primary astrocytes stimulated a1 cocktail tumor necrosis factor tnf interleukin il 1 c1q activated lps microgliaconditioned medium mcm il6 24 h expression a1special a2special markers determined using rtqpcr western blot role 5ht2br effects fluoxetine a1 reactive astrocyte measured using 5ht2br inhibitor sirna vitro aavs vivo functions downstream signaling gq protein arrestins effects fluoxetine activation a1 astrocyte determined using pharmacological inhibitor genetic knockout respectivelyresultsin study found fluoxetine inhibited activation a1 reactive astrocyte reduced abnormal behaviors cms mice well ameliorated a1 astrocyte reactivity three different stimulators primary astrocytes also showed astrocytic 5ht2br required inhibitory effects fluoxetine a1 reactive astrocyte mdd vivo vitro found functions fluoxetine activation a1 astrocyte independent either gq protein arrestin1 vitro arrestin2 pathway downstream signaling astrocytic 5ht2br mediated inhibitory effects fluoxetine a1 astrocyte reactivity primary astrocytes cms mice well improved roles fluoxetine behavioral impairments cms miceconclusionsthese data demonstrate fluoxetine restricts reactive a1 astrocyte via astrocytic 5ht2br arrestin2 pathway mouse model mdd provide novel therapeutic avenue mdd,0.0
bilateral corneal perforation caused neurotrophic keratopathy associated leprosy case report background neurotrophic keratopathy nk rare degenerative corneal disease caused damage trigeminal nerve hereby describe severe case bilateral corneal perforation due leprosy hansens disease associated nkcase presentationan 89yearold man history leprosy treated 40 years previously sanatorium developed bilateral corneal perforation due nk history bilateral persistent epithelial defects bacterial keratitis although epithelialization obtained use autologous serum eye drops progressive corneal thinning concomitant stromalysis led bilateral perforation one month treatment topical antibiotics antiinflammatory lubricants resulted healing epithelial defects corneal perforations cochetbonnet esthesiometer demonstrated total absence corneal sensation eyesconclusionsthe present case indicated irreversible nerve damage due leprosy cured 23 years ago can progress years cause bilateral corneal perforations,0.0
big deal qualitative study clinical biobank donation experience motives background success biobanking directly linked willingness people donate biological materials research storage ethical issues related patient consent essential component current biobanking agenda majority data available focused populationbased biobanks usa canada western europe donation decision process ethical applications clinical populations populations countries cultural contexts limited study aimed evaluate decisionmaking experience clinical biobank donors well psychological social motivators deterrents decision associated ethical risksmethodssemistructured interviews conducted two medical institutions st petersburg russia 20162017 among 13 donors clinical biobank pregnant women cardiac patients patients multiple sclerosis three donation organisersmedical specialists involved recruiting donors clinical biobank analysis interview data based qualitative content analysisresultsdonors clinical biobank express beliefs absence risks associated donation primary motivators donating biobank prosocial indirect reciprocity response anticipation act kind third party intrinsic motivation enhance selfesteem satisfying curiosity donation process comparability personal values high level trust biomedical research particular physician can contribute favourable decision overall decisionmaking process regarding biobank donation described quick based careful reading informed consent documents integration biobank donation decisionmaking process medical care might prompt patient donate biobank without proper consideration specific type therapeutic misconceptionthe presence unrealistic hope donation provide direct benefit third person need discoveredconclusionspatients recruited clinical biobank russia virtually concerns storage biomaterials donation decision mainly motivated prosocial attitudes factors similar motivating factors blood donation fact going inpatient treatment poor differentiation donation peoples benefit research purposes can make process obtaining consent ethically problematic,0.0
effectiveness decision aids pregnancy related decisionmaking women prepregnancy morbidity systematic review metaanalysis abstractintroductionwomen preexisting morbidity arising medical conditions previous caesarean section higher risk adverse pregnancy outcomes compared women without morbidity women often face complex pregnancyrelated decisionmaking may characterized conflicting maternal perinatal priorities aim systematic review metaanalysis assess randomised controlled trials decision aids evaluate whether effective reducing decisional conflict scores evaluate type decision aids effective women preexisting morbidity pregnancymethodswe searched medline via ovid embase via ovid cinahl via ebsco earliest entries september 2021 selected randomised controlled trials comparing patient decision aids women preexisting morbidity usual clinical practice control intervention study characteristics jadad risk bias recorded metaanalysis preexisting morbidity type performed using stata 17 data presented forest plot random effects models used calculate summary estimates substantial clinical statistical heterogeneity post mean dcs scores described sensitivity analysis presented line graph improve clinical interpretation results narrative synthesis selected studies evaluated type decision aid works circumstancesresultsten randomised controlled trials reported data 4028 women included patient decision aids evaluated women preexisting morbidity undertaking pregnancyrelated decisionmaking patient decision aids reduced decisional conflict scale scores additional 37 95 confidence interval 59 16 compared control group women preexisting medical conditions conflicted baseline greater reductions decisional conflict scale score mean difference vs control group 66 95 ci 98 33 contrast previous caesarean section mean difference 24 95 ci 48 01 limited evidence effect decision aids health outcomes decision aids reduced unwanted variation decisionmaking support across maternity settingsconclusionpatient decision aids effective tools support personalised care planning informed decisionmaking women preexisting morbidity women preexisting medical morbidity conflicted baseline likely benefit decision aids adoption aids population may lead improve adherence health outcomes warranting research,0.0
joint involvement disease activity quality life pediatric crohns disease crosssectional study background published data describe joint involvement prevalent extraintestinal manifestation affects quality life qol children crohns disease cd arthritis arthralgia rates pediatric cd patients reportedly 324 1722 respectively studies preemptive systematic screening joint involvement detailed musculoskeletal rheumatological exam lacking detailed data collection joint involvement improves understanding arthropathy relates disease activity qol measured pediatric cd activity index pcdai impactiii questionnaire study aims assess joint involvement pediatric cd correlate pcdai impactiiimethodsin crosssectional observational study pediatric gastroenterologist assessed consecutivelyseen pediatric cd patients tertiary care center patients screened prevalence current previous arthropathy including arthritis enthesitis arthralgia single experienced pediatric rheumatologist evaluated detailed musculoskeletal history joint status modified juvenile arthritis multidimensional assessment reports jamar pcdai impactiii sacroiliac mri hlab27 genetic testing also completedresultsa total 82 malefemale 121 age 137 32 years patients involved study mean disease duration time study 216 21 months eight patients newlydiagnosed 82 patients 29 35 evidence arthritis 24 revealed physical exam crosssectional screening prior documentation remaining five patients joint examination confirmed active arthritis 8 24 33 active enthesitis 1 24 4 evidence previous arthritis 15 24 625 patients hip 41 knee 38 joints commonly affected cumulative incidence arthralgia 48 39 82 46 18 39 patients arthralgia without arthritis usually affecting knee axial involvement present 10 82 12 patients joint involvement correlated severe cd disease activity specifically higher pcdai lower impactiii scores increased requirement infliximab treatment sacroiliitis hlab27 positivity insignificant factors cohortconclusionswhen rheumatologist performed assessment joint involvement pediatric cd prevalent previously reported crosssectional study arthritis associated severe cd disease activity lower qol,0.0
common incidenceage multistep model neurodegenerative diseases revisited wider general age range incidence corresponds fewer disease steps background previously collected agestratified incidence data 404 epidemiological datasets 10 neurodegenerative diseases nds namely amyotrophic lateral sclerosis als alzheimers disease ad parkinsons disease pd huntingtons disease hd fronto temporal dementia ftd dementia lewy bodies dlb parkinsonism pdm parkinsons disease dementia pdd creutzfeldtjakob disease cjd multiple sclerosis ms tested whether nd follows multistep model found number steps necessary onset nd found number common steps nds number specific steps nd built parsimony tree genealogy nds tree disclosed three groups nds stem nds less 3 steps trunk nds 57 steps crown nds 7 stepsmethodswe made multidimensional reduction previously collected agestratified incidence epidemiological data 10 nds studied general range incidence 10 nds using age sexstratified incidence data first calculated log incidence versus log age nd next calculated age intervals spread incidence nd calculated regression steps obtained multistep model versus age incidence ndsresultswe found number steps nds inversely correlated age incidence nds calculated number years required single step nd based results extended genealogy tree model nds account time needed nd step occurconclusionthe extended genealogy tree disclosed three groups nds according estimated time needed step occur stem nd hd 325 years step trunk nds als ftd pd cjd 67137 years step crown nds pdm pdd ad dlb 2338 years step thus nds cluster three groups according number steps number years step occur,0.0
ampkautophagymediated inhibition microrna30a5p alleviates morphine tolerance via socs3dependent neuroinflammation suppression background development morphine tolerance clinical challenge managing severe pain studies shown neuroinflammation critical aspect development analgesic tolerance found ampkautophagy activation suppress neuroinflammation improve morphine tolerance via upregulation suppressor cytokine signaling 3 socs3 inhibiting processing maturation microrna30a5pmethodscd1 mice utilized tailflick test evaluate morphine tolerance microglial cell line bv2 utilized investigate mechanism ampkautophagymediated posttranscriptional regulation socs3 proinflammatory cytokines measured western blotting realtime pcr levels socs3 mirnaprocessing enzymes evaluated western blotting realtime pcr immunofluorescence stainingresultsbased experimental verification mirna30a5p negatively regulate socs3 ampk activators aicar resveratrol metformin downregulated mirna30a5p found ampk activators specifically inhibited processing maturation mirna30a5p microglia degrading dicer ago2 via autophagy furthermore mirna30a5p inhibitor significantly improved morphine tolerance via upregulation scos3 mice markedly increased level socs3 spinal cord mice subsequently inhibited morphineinduced phosphorylation nfb p65 addition mirna30a5p inhibitor decreased levels il1 tnf caused morphine microgliaconclusionampkautophagy activation suppresses neuroinflammation improves morphine tolerance via upregulation socs3 inhibiting mirna30a5p,0.0
development standard care patients valosincontaining protein associated multisystem proteinopathy abstractvalosincontaining protein vcp associated multisystem proteinopathy msp rare inherited disorder may result multisystem involvement varying phenotypes including inclusion body myopathy pagets disease bone pdb frontotemporal dementia ftd parkinsonism amyotrophic lateral sclerosis als among others international multidisciplinary consortium 40+ experts neuromuscular disease dementia movement disorders psychology cardiology pulmonology physical therapy occupational therapy speech language pathology nutrition genetics integrative medicine endocrinology convened patient advocacy organization cure vcp disease december 2020 develop standard care heterogeneous underdiagnosed disease achieve goal working groups collaborated generate expert consensus recommendations 10 key areas genetic diagnosis myopathy ftd pdb als charcot marie tooth disease cmt parkinsonism cardiomyopathy pulmonology supportive therapies nutrition supplements mental health april 2021 facilitated discussion working groups conclusions consensus building techniques enabled final agreement proposed standard care vcp patients timely referral specialty neuromuscular center recommended aid efficient diagnosis vcp msp via singlegene testing case known familial vcp variant multigene panel sequencing undifferentiated cases additionally regular ongoing multidisciplinary team follow essential proactive screening management secondary complications goal consortium raise awareness vcp msp expedite time accurate diagnosis define gaps inequities patient care initiate appropriate pharmacotherapies supportive therapies optimal management elevate recommended best practices guidelines multidisciplinary care internationally,0.0
nanotechnologybased advances efficient delivery melatonin abstractn 2 5methoxy1hindol3yl ethyl simply melatonin biogenic amine produced pineal gland recently recognized various organs broad range biological function melatonin considered therapeutic agent high efficacy treatment multiple disorders cancer degenerative disorders immune disease however since melatonin can affect receptors cellular membrane nucleus can act antioxidant molecule unwanted effects may observed administration therefore entrapment melatonin biocompatible biodegradable safe nanodelivery systems can prevent degradation circulation decrease toxicity increased halflife enhanced pharmacokinetic profile leading improved patient compliance nanoparticles used deliver melatonin multiple studies present article aims cumulatively illustrate findings,0.0
sequential endoscopic robotassisted surgical solutions rare fungal spondylodiscitis secondary lumbar spinal stenosis subsequent discal pseudocyst causing acute cauda equina syndrome case report background fungal spondylodiscitis rare infectious disease secondary lumbar spinal stenosis postoperative discal pseudocyst even rarer surgical interventions disputed yet endoscopic robotassisted techniques may helpful different circumstancescase presentationa 62yearold female diagnosed infectious spondylodiscitis l4 5 level posterolateral endoscopic debridement performed invalid conservative therapy causative organism culture revealed rare fungus candida tropicalis secondary spinal stenosis refractory radiculopathy occurred almost 3 years first surgery successful endoscopic surgery implemented aiming decompress nerve minimally invasive way however 2 months later patient manifested severe acute cauda equina syndrome radiological examinations suggested rare postoperative discal pseudocyst laminectomy followed pseudocystectomy applied achieve thorough decompression innovative double trajectory system simultaneous traditional pedicle screw cortical bone trajectory screw accompanied posterolateral fusion designed executed professional robotassisted systemconclusionendoscopic robotassisted techniques may provide alternative solutions fungal spondylodiscitis accompanied sequelae,0.0
case multiple sclerosis protracted course covid19 infect disord drug targets 2022 jan 28 doi 102174 1871526522666220128121855 online ahead printabstractbackground reported case multiple sclerosis ms persistent symptomatic covid19 complicated newappearing severe pneumonia 40 days disease onsetcase presentation 38yearold man history multiple sclerosis referred hospital fever shaking chills cough dyspnea history patient developed mild covid19 40 days ago 7 days disease onset covid symptoms subsided partially fatigue myalgia intermittent fever loss taste smell continued physical examinations oral temperature 394 c respiratory distress blood oxygen saturation room air 90 spiral chest ct scan performed revealed bilateral ground glass alveolar opacities favor covid19 pneumonia result rtpcr test sarscov2 reported positive subsequently current ms medication rituximab received last dose rituximab two months developing covid19 patient admitted covid ward put remdesivir subcutaneous interferonbeta1b dexamethasone improved gradually discharged hospital favorable condition 10 days patient rare protracted disease course presumed prolong high degree fever 38 c patient beyond diagnosis postcovid19 syndrome compatible persistent infectionconclusion although immunocompromised patients effectively clear sarscov2 infection case report highlights risk persistent infection associated recurrence diseasepmid35088680 doi102174 1871526522666220128121855,0.0
engineered extracellular vesicles encapsulated bryostatin1 therapy neuroinflammation nanoscale 2022 jan 28 doi 101039 d1nr05517h online ahead printabstracttargeted effective drug delivery central nervous system cns lesions major challenge treatment multiple sclerosis ms extracellular vesicles evs great promise drug delivery nanosystem given unique characteristics including strong cargoloading capacity low immunogenicity high biocompatibility inherent stability high delivery efficiency ease manipulation bloodbrain barrier bbb penetration clinical applications however limited insufficient targeting capability dilution effects upon systemic administration neural stem cells nscs provide abundant source evs remarkable capacity selfrenewal developed novel therapeutic strategy local delivery treatment using evps derived nscs expression cns lesion targeting ligandpdgfr furthermore used evps targeting carrier encapsulating bryostatin1 bryo1 natural compound remarkable antiinflammation ability data showed bryo1 delivered evps stable concentrated cns native bryo1 systemic injection low dosage 1 108 particles evps + bryo1 versus evps bryo1 administration significantly ameliorated clinical disease development decreased infiltration proinflammatory cells blocked myelin loss astrogliosis protected bbb integrity altered microglia proinflammatory phenotype cns eae mice taken whole study showed engineered evs cns targeting capacity provides potentially powerful therapeutic effects treatment various neuroinflammatory diseasespmid35088795 doi101039 d1nr05517h,1.0
identification genetic mechanism associates l3mbtl3 multiple sclerosis hum mol genet 2022 jan 28ddac009 doi 101093 hmg ddac009 online ahead printabstractmultiple sclerosis ms complex demyelinating disease central nervous system one challenges postgwas era understand molecular basis statistical associations reveal gene networks potential therapeutic targets l3mbtl3 locus associated ms risk gwas identify causal variant locus performed fine mapping cohort 3440 ms patients 1688 healthy controls variant best explained association rs6569648 p 413e10 071 95 ci 064079 tagged rs7740107 located intron 7 l3mbtl3 rs7740107 t variant reported best expression splice quantitative trait locus eqtl sqtl region 35 human gtex tissues sequencing rna blood 17 ms patients quantification digital qpcr determined eqtl sqtl originated expression novel short transcript starting intron 7 near rs7740107 short transcript translated three proteins starting different translation initiation codons nterminal truncated proteins lacked region l3mbtl3 interacts transcriptional regulator rbpj recombination signal binding protein immunoglobulin kappa j region turn regulates notch signaling pathway data functional studies suggest genetic mechanism underlying ms association rs7740107 affects expression l3mbtl3 isoforms might also involve notch signaling pathwaypmid35088080 doi101093 hmg ddac009,1.0
cerebrospinal fluid biomarkers cognitive functions multiple sclerosis diagnosis j neurol 2022 jan 28 doi 101007 s00415021109454 online ahead printabstractcognitive impairment ci frequent disabling symptom multiple sclerosis ms axonal damage may contribute ci development early stages nevertheless biomarkers moment available track ci ms patients aimed explore correlation cerebrospinal fluid csf axonal biomarkers particular lightchain neurofilaments nfl tau betaamyloid protein abeta ms patients ci diagnosis 62 newly diagnosed ms patients enrolled cognition evaluated using brief international cognitive assessment ms bicams battery csf nfl abeta tau levels determined commercial elisa patients ci 451 differ demographic clinical mri characteristics except lower educational level displayed greater neurodegeneration exhibiting higher mean csf tau protein 1621 5296 pg ml versus 1322 6386 pg ml p003 differences observed abeta nfl number impaired tests tau significantly correlated r032 p001 tau higher particular patients slowed information processing speed ips p0006 linear regression analysis accounting edss mri ms subtype confirmed tau weak predictor ips cognitive impairment conclusion ci important burden quality life ms patients looked even diagnosis axonal damage biomarkers particular tau seem reflect cognition impairment early stagespmid35088141 doi101007 s00415021109454,0.0
changes trunk head acceleration 6minute walk test relation falls risk adults multiple sclerosis exp brain res 2022 jan 28 doi 101007 s00221021062961 online ahead printabstractfor persons multiple sclerosis ms general decline neuromuscular function underlies diminished balance impaired gait consequently increased risk falling gait optimal control head motion important feature achieved partly control trunkneck region dampen gaitrelated oscillations primary aim study examine effect performing 6minute walk test 6mwt head neck trunk accelerations individuals ms addressed using repeated measures generalized linear model also interested assessing whether 6mwt impact persons falls risk specific physiological measures related falls finally relation amplitude ie mean rms head trunk accelerations falls risk examined using linear regression main results course 6mwt individuals progressively slowed coupled concurrent increase gaitrelated upper body accelerations ps 005 despite increased acceleration significant changes attenuation trunk head observed indicating persons able maintain optimal level control oscillations performing 6mwt also negative impact posture falls risk significantly increasing following test p 005 interestingly overall falls risk values strongly linked vertical accelerations trunk head average walking speed 6mwt overall performing 6mwt leads changes walking speed upper body acceleration patterns increases overall falls riskpmid35088117 doi101007 s00221021062961,0.0
fast gray matter acquisition t1 inversion recovery sequence deep brain stimulation introducing rubral wing dentatorubrothalamic tract depiction tremor control neuromodulation 2022 jan 15s10947159 21 069488 doi 101016 jneurom202111015 online ahead printabstractbackground dentatorubrothalamic tract drt currently considered potential target deep brain stimulation dbs various types tremor however tractography depiction can vary depending included brain regions fast gray matter acquisition t1 inversion recovery fgatir sequence excellent delineation gray white matter possibly provides anatomical identification rubrothalamic drt fibersobjective study aimed evaluate fgatir sequence comparison drt depiction electrode localization effectiveness dbs therapymaterials methods patients dbs therapy medicationrefractory tremor fgatir sequence evaluated depiction thalamus red nucleus rn rubrothalamic connections deterministic tractography drt electrode localization tremor control compared essential tremor rating scale used assess hand tremor tremor control considered successful complete tremor suppression grade 0 almost complete suppression grade 1 observedresults postoperative phase evaluated 14 patients underwent drtguided dbs 12 patients essential tremor one tremordominant parkinson disease one multiple sclerosis representing 24 trajectories mean followup 113 months range 619 months fgatir sequence provided clear delineation hypointense white matter tract within hyperintense thalamus coronal plane tract readily recognizable rubral wing round rn base lateral triangular convergence deterministic drt depiction consistently situated within rubral wing number active contacts located within drt rubral wing 22 92 16 73 showed successful tremor controlconclusions fgatir sequence offers visualization rubrothalamic connections form drt readily recognizable rubral wing coronal plane sequence contributes tractographic depiction drt provides direct anatomical dbs target area tremor controlpmid35088745 doi101016 jneurom202111015,0.0
trends use diseasemodifying therapies among reproductiveaged women multiple sclerosis united states 20102019 pharmacoepidemiol drug saf 2022 jan 27 doi 101002 pds5411 online ahead printabstractpurpose multiple sclerosis ms chronic disease central nervous system disproportionately affects women typical onset reproductive age several diseasemodifying therapies dmts fdaapproved slow disease progression indicated use pregnancy objective describe trends time 20102019 monthly point prevalence dmt use among reproductiveage women overall generic namemethods study used administrative claims data us 20092019 identify women age 1545 ms continuous insurance coverage 12 months dmts identified using prescription fills procedural claims alemtuzumab daclizumab dimethyl fumarate fingolimod glatiramer acetate interferon beta mitoxantrone natalizumab ocrelizumab teriflunomide monthly prevalent use defined 1 days supply dmt month age regionstandardized monthly prevalence estimated nonparametricallyresults among 42 281 reproductiveaged women 818 179 personmonths dmt use increased minimum monthly prevalence 493 february 2011 maximum 587 april 2019 2010 prevalence injectable dmts 431 compared 25 oral dmts 2014 however oral dmts 265 surpassed injectable dmts 237 common route administration recent data available december 2019 common dmts dimethyl fumarate glatiramer acetate fingolimodconclusions dmt use among reproductiveaged women rapidly evolved past decade collaborative treatment decision making women ms clinicians may help optimize ms care improve dmt uptake reproductive yearspmid35088492 doi101002 pds5411,0.0
bridging callosal gap gait corpus callosum white matter integrity#39 s role lower limb coordination brain imaging behav 2022 jan 28 doi 101007 s11682021006127 online ahead printabstractbilateral coordination lower extremities essential component mobility corpus callosum bridges two hemispheres brain integral coordination complex movements aim project assess structural integrity transcallosal sensorimotor fiber tracts identify associations gait coordination using novel methods ecologically valid mobility assessments persons multiple sclerosis age gendermatched neurotypical adults neurotypical adults n 29 persons multiple sclerosis n 27 underwent gait diffusion tensor imaging assessments lower limb coordination via phase coordination index radial diffusivity indirect marker myelination applied primary outcome measures persons multiple sclerosis possessed poorer transcallosal white matter microstructural integrity sensorimotor fiber tracts compared neurotypical adults persons multiple sclerosis demonstrated significantly poorer bilateral coordination lower limbs overground walking comparison age gendermatched neurotypical cohort finally bilateral coordination lower limbs significantly associated white matter microstructural integrity dorsal premotor primary motor fiber bundles persons multiple sclerosis neurotypical adults analysis revealed persons multiple sclerosis exhibit poorer transcallosal microstructural integrity neurotypical peers furthermore structural deficits correlated poorer consistency accuracy gait multiple sclerosis together results emphasize importance transcallosal communication gait coordination multiple sclerosispmid35088352 doi101007 s11682021006127,1.0
measles summarymeasles highly contagious potentially fatal vaccinepreventable disease caused measles virus symptoms include fever maculopapular rash least one cough coryza conjunctivitis although vaccinated individuals can milder even symptoms laboratory diagnosis relies largely detection specific igm antibodies serum dried blood spots oral fluid detection viral rna throat nasopharyngeal swabs urine oral fluid complications can affect many organs often include otitis media laryngotracheobronchitis pneumonia stomatitis diarrhoea neurological complications uncommon serious can occur soon acute disease eg acute disseminated encephalomyelitis months even years later eg measles inclusion body encephalitis subacute sclerosing panencephalitis patient management mainly involves supportive therapy vitamin supplementation monitoring treatment secondary bacterial infections antibiotics rehydration case severe diarrhoea specific antiviral therapy treatment measles disease control largely depends prevention however despite availability safe effective vaccine measles still endemic many countries causes considerable morbidity mortality especially among children resourcepoor settings low case numbers reported 2020 worldwide resurgence measles 2017 2019 interpreted cautiously owing effect covid19 pandemic disease surveillance disrupted vaccination activities pandemic increase potential another resurgence measles near future effective timely catchup vaccination campaigns strong commitment leadership sufficient resources will required mitigate threat,0.0
physical exercise may improve problemsolving skills emotional intelligence patients relapsingremitting multiple sclerosis crosssectional study abstractbackgroundmultiple sclerosis disease can reduce quality life physical disability neuropsychiatric disorders cognitive dysfunctions therefore multiple sclerosis treatment include treatments cognitive neuropsychiatric disorders pharmacological treatments study aimed examine effects exercise neuropsychiatric disorders problemsolving skills emotional intelligence multiple sclerosis patientsmethodsthirtysix female relapsingremitting multiple sclerosis patients aged 1845 years expanded disability status scale 13 diagnosed definitive multiple sclerosis according revised mcdonald criteria included study participants completed outcome measures 12week exercise program demographic clinical information participants obtained baseline neurological examinations performed graded exercise testing bicycle ergometer performed determine aerobic capacity short form12 version 2 hospital anxiety depression scale modified fatigue impact scale problemsolving inventory emotional intelligence scale evaluated exercise program participantsresultswhile significant increase observed hrpeak values participants exercise p005 vo2max values also showed highly significant difference compared pretreatment values p001 significant difference detected mental subparameter short form12 p005 high level significant difference found physical subparameter p001 significant difference observed hospital anxiety depression scale anxiety subparameter p005 significant difference found depression subparameter p001 significant difference modified fatigue impact scale physical cognitive subparameters compared pretreatment p001 significant difference observed emotional intelligence scale total score treatment p001 conclusionsthe results study showed exercise relapsingremitting multiple sclerosis patients provided significant improvements emotional intelligence improved neuropsychiatric parameters increased problemsolving skills addition best knowledge study first study literature investigate effect physical activity exercises problemsolving skills multiple sclerosis patients,0.0
nad p h quinone oxidoreductase 1 attenuates oxidative stress apoptosis regulating sirt1 diabetic nephropathy background diabetic nephropathy dn one main complications diabetes oxidative stress plays important role progression nad p h quinone oxidoreductase 1 nqo1 protects cells oxidative stress toxic quinone damage present study aimed investigate protective effects underlying mechanisms nqo1 diabetesinduced renal tubular epithelial cell oxidative stress apoptosismethodsin vivo kidneys db db mice type 2 diabetes model infected adenoassociated virus induce nqo1 overexpression vitro human renal tubular epithelial cells hk2 cells transfected nqo1 pcdna31 + cultured high glucose hg gene protein expression assessed quantitative realtime pcr western blotting immunofluorescence analysis immunohistochemical staining reactive oxygen species ros examined mitosox red flow cytometry tunel assays used measure apoptosisresultin vivo nqo1 overexpression reduced urinary albumin creatinine ratio uacr blood urea nitrogen bun level db db mice results revealed nqo1 overexpression significantly increase ratio nad+ nadh silencing information regulator 1 sirt1 expression block tubular oxidative stress apoptosis diabetic kidneys vitro nqo1 overexpression reduced generation ros nadph oxidase 1 nox1 nox4 bax bcl2 ratio expression cleaved caspase3 increased nad+ nadh levels sirt1 expression hk2 cells hg conditions however effects reversed sirt1 inhibitor ex527conclusionsall data suggest nqo1 protective effect oxidative stress apoptosis dn may mediated regulation sirt1 increasing intracellular nad+ nadh levels therefore nqo1 may new therapeutic target dn,0.0
processing speed working memory predicted components successful aging hunt study background research demonstrated cognitive heterogeneity occurs aging within individuals purpose study explore whether cognitive heterogeneity aging related subgroups successful usual agingmethodparticipants representative sample normal older adults n 65 age range 7089 years subjects participated third phase nordtrndelag health survey hunt3 completed subtests wechsler memory scale wmsiii wechsler adult intelligence scale waisiii successful aging defined four ways study 1 absence disease 2 high functioning 3 active engagement life 4 three components combined five domains memory intelligence functions investigated using linear regression analysis group membership successful versus usual aging predictors age sex education correlatesresultsprocessing speed performance correlated successful aging component absence disease younger age female sex working memory performance correlated successful aging component absence disease years education performance domains verbal visuospatial episodic memory related successful aging definition age consistent negative effect processing speed domain successful aging definitions education positively linked cognitive performance verbal working memory domains female positively linked processing speed episodic memoryconclusionsprocessing speed working memory linked successful aging defined absence disease components successful aging ie domainspecific contrast cognitive domains related components successful aging,0.0
comparison modified facet joint fusion posterolateral fusion treatment lumbar degenerative diseases retrospective study abstractobjectiveto investigate safety effectiveness modified facet joint fusion treatment lumbar degenerative diseases compare posterolateral fusionmethodsa total 77 adult patients lumbar degenerative disease diagnosed january 2017 february 2019 considered present retrospective nonrandomized controlled study patients divided two groups according fusion technique used surgery posterolateral fusion plf group n 42 modified facet joint fusion mff group n 35 fusion rate oswestry disability index odi score visual analog scale vas score back pain leg pain japanese orthopedic association joa score european quality life5 dimensions eq5d score length hospital stay length operation intraoperative blood loss cost hospitalization complications reoperations compared 2 groupsresultsall patients underwent successful surgery followed significant differences found age sex bmi length hospital stay length operation cost hospitalization significant differences preoperative postoperative odi vas joa eq5d scores mff plf groups however fusion rate mff group higher plf group p 005 whats mff group less intraoperative blood loss plf group p 005 complications related iatrogenic nerve injury vascular injury epidural hematoma intravertebral infection internal fixation occur either group none patients required reoperationconclusionsmodified facet joint fusion safe efficient treatment lumbar degenerative disease fusion rate mff higher plf intraoperative blood loss mff less plf addition therapeutic effect mff worse plf therefore mff technique can promoted clinical treatment,0.0
brain macrophages acquire distinct transcriptomes multiple sclerosis lesions normal appearing white matter abstractmultiple sclerosis ms disease central nervous system characterized inflammation focal areas demyelination ultimately resulting axonal degradation neuronal loss several lines evidence point towards role microglia brain macrophages disease initiation progression exactly lesion formation triggered currently unknown characterized early changes ms brain tissue transcriptomic analysis normal appearing white matter nawm found nawm characterized enriched expression genes associated inflammation cellular stress derived brain macrophages single cell rna sequencing confirmed stress response brain macrophages nawm identified specific microglia macrophage subsets different stages demyelinating lesions identified phagocytic activated microglia cam clusters associated various ms lesion types overall changes microglia macrophages associated lesion development ms brain tissue may provide therapeutic targets limit lesion progression demyelination,1.0
circular rnas glioblastoma multiforme focus molecular mechanisms abstractglioblastoma multiforme gbm deadly almost incurable brain cancer invasive form cns tumors affects children adult population accounts approximately half primary brain tumors despite remarkable advances neurosurgery radiotherapy chemotherapeutic approaches cell heterogeneity numerous genetic alterations cell cycle control cell growth apoptosis cell invasion result undesirable resistance therapeutic strategies thereby median survival duration gbm patients unfortunately still less two years identifying new therapeutics employing combination therapies may considered wonderful strategies gbm regard circular rnas circrnas tumor inhibiting stimulating rna molecules can regulate cancerdeveloping processes including cell proliferation cell apoptosis invasion chemoresistance hereupon molecules introduced potentially effective therapeutic targets defeat gbm current study aims investigate fundamental molecular cellular mechanisms association circrnas involved gbm pathogenesis among multiple mechanisms pi3k akt mtor wnt catenin mapk signaling angiogenic processes metastatic pathways will thoroughly discussed provide comprehensive understanding role circrnas pathophysiology gbm video abstract,0.0
costeffectiveness analysis rituximab versus natalizumab patients relapsing remitting multiple sclerosis abstractintroductionmultiple sclerosis ms inflammatory disease myelin sheaths nerve cells brain spinal cord responsible communication destroyed cause physical signs symptoms according studies anticd20 monoclonal antibodies significant results treatment disease thus aim present study determine costeffectiveness rituximab natalizumab patients rrms southern iran 2020methodsthis economic evaluation including costeffectiveness analysis markov model lifetime horizon used study sample consisted 120 patients randomly selected among referred ms association special diseases unit shiraz university medical sciences study costs collected societal perspective outcomes obtained form quality adjusted life years qaly mean relapse rate treeage pro 2020 excel 2016 software used data analysisresultsthe comparative study rituximab natalizumab showed patients receiving rituximab lower costs 58 30793 vs 354 17485 qalys 777 vs 765 addition incidence relapse rituximab lower compared natalizumab 115 vs 257 probabilistic oneway sensitivity analysis showed robustness results scatter plots also showed rituximab costeffective patients 100 simulations threshold 37 641discussion conclusionaccording results study rituximab higher costeffectiveness natalizumab therefore priority rrms patients compared natalizumab reduced treatment costs increased effectiveness,1.0
chronic kidney disease mediates cardiac dysfunction associated increased resident cardiac macrophages background leading cause death endstage kidney disease related cardiovascular disease macrophages known involved chronic kidney disease ckd heart failure however role development cardiorenal syndrome less clear thus sought investigate role macrophages uremic cardiac diseasemethodswe assessed cardiac response two experimental models ckd tested macrophage chemokine implication monocytopenic ccr2 anticxcl10 treated mice quantified cxcl10 human ckd plasma tested response human ipscderived cardiomyocytes primary cardiac fibroblasts serum ckd donorsresultswe found reduced kidney function resulted expansion cardiac macrophages particular local proliferation resident populations influx circulating monocytes contributed increase identified cxcl10 crucial factor cardiac macrophage expansion uremic disease humans found increased plasma cxcl10 concentrations advanced ckd identified production cxcl10 cardiomyocytes cardiac fibroblastsconclusionsthis study provides new insight role innate immune system uremic cardiomyopathy,0.0
effects repetitive transcranial magnetic stimulation multiple sclerosis systematic review metaanalysis abstractobjective study aims quantitatively evaluate summarize effectiveness repetitive transcranial magnetic stimulation rtms treatment patients multiple sclerosis ms methods pubmed embase web science cochrane database systematic reviews cbm cnki wanfang databases searched randomized controlled trails rcts inception july 10 2021 rcts met inclusion exclusion criteria included study revman software used metaanalysis outcome indicators included scores fatigue severity scale fss modified ashworth scale mas h m amplitude ratio soleus h reflex p 005 difference considered significantresults total 10 articles included study 8 quantitative synthesis metaanalysis showed shortterm effect rtms treatment mas better control treatment 95 ci 127 025 p0004 compared control group effect rtms treatment h m ratio showed significant effect 95 ci 012 003 p0002 treatment effect fss significant 95 ci 487 128 p025 conclusions results provide preliminary evidence treatment patients ms rtms especially improving spasticity research needed evaluate effects fatigue,0.0
alterations hostgut microbiome interactions multiple sclerosis summarybackgroundmultiple sclerosis ms complex genetic immune metabolic pathophysiology recent studies implicated gut microbiome ms pathogenesis however interactions microbiome host immune system metabolism diet studied time disordermethodswe performed sixmonth longitudinal multiomics study 49 participants 24 untreated relapse remitting ms patients 25 age sex race matched healthy control individuals gut microbiome composition function characterized using 16s metagenomic shotgun sequencing flow cytometry used characterize blood immune cell populations cytokine profiles circulating metabolites profiled untargeted uplcms fourday food diary recorded capture habitual dietary pattern study participantsfindingstogether changes blood immune cells metagenomic analysis identified number gut microbiota decreased ms patients compared healthy controls microbiota positively negatively correlated degree disability ms patients ms patients demonstrated perturbations blood metabolome linoleate metabolic pathway fatty acid biosynthesis chalcone dihydrochalcone 4nitrocatechol methionine global correlations multiomics demonstrated disrupted immunemicrobiome relationship positive blood metabolomemicrobiome correlation ms specific feature association analysis identified potential correlation network linking meat servings decreased gut microbe b thetaiotaomicron increased th17 cell greater abundance meatassociated blood metabolites microbiome metabolome profiles remained stable six months ms control individualsinterpretationour study identified multisystem alterations gut microbiota immune blood metabolome ms patients global individual feature level multiomics data integration deciphered potential important biological network links meat intakes increased meatassociated blood metabolite decreased polysaccharides digesting bacteria increased circulating proinflammatory markerfundingthis work supported washington university st louis institute clinical translational sciences funded part grant number # ul1 tr000448 national institutes health national center advancing translational sciences clinical translational sciences award zhou y piccio l lovettracke tarr pi r01 ns10263304 zhou y piccio l leon harriet felman fund human ms research piccio l cross ah cantoni c supported national ms society career transition fellowship ta180531003 donations whitelaw terry jr valerie terry fund ghezzi l supported italian multiple sclerosis society research fellowship fism 2018 b 1 national multiple sclerosis society postdoctoral fellowship fg190734474 anne cross supported manny rosalyn rosenthaldr john l trotter ms center chair neuroimmunology barnesjewish hospital foundation content solely responsibility authors necessarily represent official views national institutes health,0.0
changes serum neurofilament light chain levels following narrowband ultraviolet b phototherapy clinically isolated syndrome brain behav 2022 jan 27e2494 doi 101002 brb32494 online ahead printabstractobjective determine whether serum neurofilament light chain snfl levels suppressed patients clinically isolated syndrome cis following narrowband ultraviolet b phototherapy uvbpt methods snfl levels measured using sensitive singlemolecule array assay baseline 12 months 17 patients cis 10 received uvbpt compared healthy control hc early relapsing remitting multiple sclerosis rrms group snfl levels correlated magnetic resonance imaging total lesion volume lv determined using icobrain version 441 clinical outcomesresults baseline median snfl levels significantly higher cis 206 pg ml interquartile range iqr 1371614 rrms groups 366 pg ml iqr 1622122 hc 107 pg ml iqr 49215 p 012 p 0002 respectively strongly correlated t2 t1 lv 12 months r 800 p 014 r 833 p 008 respectively cis group analysis changes snfl levels time cis group showed significant cumulative suppressive effect uvbpt first 3 months uvbpt 106 vs nonuvbpt +583 p 04 following levels two groups converged continued fallconclusions findings provide basis studies determine utility snfl levels marker neuroaxonal damage cis early ms assessing efficacy new therapeutic interventions uvbptpmid35084124 doi101002 brb32494,0.0
optic neuritis aetiopathogenesis diagnosis prognosis management rev neurol 2022 feb 1 74 3 93104 doi 1033588 rn74032021473abstractthe main causes optic neuritis multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd myelin oligodendrocyte glycoprotein antibody disease also known mogad screening negative can speak idiopathic although diagnosis provisional can diagnosed clinically paraclinical tests routinely required confirm however tests magnetic resonance imaging mri visual evoked potentials vep optical coherence tomography oct can lend support diagnosis clinical presentation atypical use new mri sequences oct multifocal veps determination neurofilaments allowed used model remyelination neuroprotection leading phase ii clinical trials drugs opicinumab clemastine phenytoin simvastatin shown positive results however clinical effect remains defined accepted corticosteroids improve longterm prognosis although retrospective studies suggest therapeutic window onset symptoms plasmapheresis also shown effective patients review will address basic aspects management fundamental context ms nmosd mogad emphasis etiopathogenic diagnostic prognostic therapeutic developmentspmid35084734 doi1033588 rn74032021473,1.0
r ketamine ameliorates demyelination facilitates remyelination cuprizonetreated mice role gutmicrobiotabrain axis neurobiol dis 2022 jan 24105635 doi 101016 jnbd2022105635 online ahead printabstractmultiple sclerosis ms common demyelinating disease attacks central nervous system recently reported new antidepressant r ketamine ameliorate disease progression experimental autoimmune encephalomyelitis model ms cuprizone cpz used produce demyelination resembles demyelination ms patients study undertaken investigate whether r ketamine affect demyelination cpztreated mice remyelination cpz withdrawal repeated treatment r ketamine 10 mg kg day twice weekly 6 weeks significantly ameliorated demyelination activated microglia brain compared salinetreated mice furthermore pretreatment ana12 trkb antagonist significantly blocked beneficial effects r ketamine demyelination activated microglia brain cpztreated mice 16s rrna analysis showed r ketamine significantly improved abnormal composition gutmicrobiota decreased levels lactic acid cpztreated mice addition significant correlations demyelination microglial activation brain relative abundance several microbiome suggesting link gut microbiota brain interestingly r ketamine facilitate remyelination brain cpz withdrawal conclusion study suggests r ketamine ameliorate demyelination brain cpztreated mice trkb activation gutmicrobiotamicroglia crosstalk may play role demyelination cpztreated mice therefore likely r ketamine new therapeutic drug mspmid35085752 doi101016 jnbd2022105635,1.0
fitness physical activity exercise multiple sclerosis systematic review current evidence interactions disease activity progression j neurol 2022 jan 27 doi 101007 s00415021109356 online ahead printabstractbackground moderate high level physical activity including regular exercise represents established behavioral rehabilitative approach persons multiple sclerosis pwms although increasingly proposed limit disease activity progression highquality evidence lackingobjective objective study provide valuable information ms clinicians researchers systematically evaluating current state evidence whether exercise interventions affect established clinical measures disease activity progression pwms ie edss relapse rate lesion load brain volume msfc ii physical activity fitness level interact measuresmethods literature search conducted medline embase cinahl sportdiscus evaluation evidence quality done based standards published american academy neurologyresults likely exercise improves msfc score whereas edss score lesion load brain volume likely remain unchanged intervention period possible exercise decreases relapse rate results crosssectional studies indicate beneficial effects high physical activity fitness level clinical measures however corroborated high evidence qualityconclusions supportive diseasemodifying effect exercise pwms concluded rather low evidence quality existing rcts underlines need conduct welldesigned studies assessing different measures disease activity progression primary end points major limitation short intervention duration existing studies limits meaningful exerciseinduced effects disability measures findings crosssectional studies difficult contextualize regarding clinical importance due solely associative character low evidence qualityprospero registration number crd42020188774pmid35084560 doi101007 s00415021109356,0.0
web portals patients chronic diseases scoping review functional features theoretical frameworks telerehabilitation platforms j med internet res 2022 jan 27 24 1 e27759 doi 102196 27759abstractbackground covid19 pandemic required increased need rehabilitation activities applicable patients chronic diseases telerehabilitation several advantages including reducing clinic visits patients vulnerable infectious diseases digital platforms often used assist rehabilitation services patients remote settings although web portals medical use existed years technology telerehabilitation remains novel methodobjective scoping review investigated functional features theoretical approaches web portals developed telerehabilitation patients chronic diseasesmethods pubmed web science reviewed identify articles associated telerehabilitation 477 nonduplicate articles reviewed 35 involving 14 portals retrieved scoping review functional features targeted diseases theoretical approaches portals studiedresults 14 portals targeted patients chronic obstructive pulmonary disease cardiovascular osteoarthritis multiple sclerosis cystic fibrosis diseases stroke breast cancer survivors monitoring data tracking communication functions common followed exercise instructions diary selfreport features several theoretical approaches behavior change techniques motivational techniques found utilizedconclusions web portals unify display multiple types data effectively provide various types information asynchronous correspondence favorable synchronous realtime interactions data acquisition often required assistance digital tools various functions patientcentered principles behavior change strategies motivational techniques observed better support shifting healthier lifestyle findings suggested web portals telerehabilitation provided entrance rehabilitation programs also reinforced participantcentered treatment adherence rehabilitation lifestyle changes timepmid35084355 doi102196 27759,0.0
comparative study brain fmri olfactory stimulation neuromyelitis optica spectrum disease multiple sclerosis front neurosci 2022 jan 10 15813157 doi 103389 fnins2021813157 ecollection 2021abstractobjective observe characteristics brain fmri olfactory stimulation patients neuromyelitis optica spectrum disease nmosd multiple sclerosis ms compare differences brain functional activation areas patients nmosd ms explore characteristics olfactoryrelated brain networks nmosd ms methods nineteen patients nmosd 16 patients ms met diagnostic criteria recruited 19 healthy controls matched sex age recruited olfactory function participants assessed using visual analog scale vas olfactory stimulation alternately performed using volatile body lavender rose solution difference brain activation evaluated tasktaste fmri scanning simultaneously results activation intensity weaker nmosd group healthy controls including left rectus right superior temporal gyrus left cuneus activation intensity stronger nmosd controls left insula left middle frontal gyrus p 005 activation intensity weaker ms group healthy controls bilateral hippocampus right parahippocampal gyrus right insula left rectus gyrus right precentral gyrus stronger left paracentral lobule among ms controls p 005 compared ms group activation intensity nmosd group weaker right superior temporal gyrus left paracentral lobule stronger among nmosd group bilateral insula bilateral hippocampus bilateral parahippocampal gyrus left inferior orbital gyrus left superior temporal gyrus left putamen left middle frontal gyrus p 005 conclusion olfactoryrelated brain networks altered patients differences olfactoryrelated brain networks may provide new reference index clinical differentiation disease evaluation nmosd ms moreover studies neededpmid35082598 pmcpmc8785660 doi103389 fnins2021813157,0.0
feel heal negative emotion differentiation promotes medication adherence multiple sclerosis front psychol 2022 jan 10 12687497 doi 103389 fpsyg2021687497 ecollection 2021abstractmultiple sclerosis ms debilitating chronic autoimmune disease central nervous system results lower quality life medication adherence important reducing relapse disease progression msrelated symptoms particularly early stages ms however adherence may impacted negative emotional states therefore important identify protective factors past research suggests ability discriminate negative emotional states also known negative emotion differentiation ned may protective enactment maladaptive riskrelated behaviors however less known ned may promote adaptive health behaviors medication adherence utilizing weekly diaries investigated whether ned moderates association negative affect medication adherence rates across 58 weeks among patients n 27 newly diagnosed ms following mcdonald criteria results revealed ned significantly moderated relationship negative affect medication adherence specifically greater negative affect associated lower adherence individuals reporting low ned however link disappeared reporting moderate high ned building upon past research findings suggest ned may promote adaptive health behaviors important clinical implications treatment management chronic illnesspmid35082708 pmcpmc8784965 doi103389 fpsyg2021687497,0.0
identification let7f mir338 plasmabased biomarkers sporadic amyotrophic lateral sclerosis using metaanalysis empirical validation sci rep 2022 jan 26 12 1 1373 doi 101038 s41598022050674abstractamyotrophic lateral sclerosis als lethal neurodegenerative disease cases occurs sporadic sals disease curable pathogenesis mechanisms well understood yet given intricacy underlying molecular interactions heterogeneity als discovery molecules contributing disease onset progression will open new avenue advancement early diagnosis therapeutic intervention conducted metaanalysis 12 circulating mirna profiling studies using robust rank aggregation rra method followed enrichment analysis experimental verification identified mir451a let7f5p metasignature mirnas whose targets involved critical pathogenic pathways underlying als including foxo signaling pathway mapk signaling pathway apoptosis systematic review 7 circulating gene profiling studies elucidated 241 genes upregulated sals circulation concomitant targets metasignature mirnas proteinprotein interaction ppi network analysis candidate targets using mcode algorithm revealed main subcluster involved multiple cascades eventually leads apoptosis including positive regulation neuron apoptosis besides validated metaanalysis results using rtqpcr indeed relative expression analysis verified let7f5p mir3383p significantly downregulated upregulated biomarkers plasma sals patients respectively receiver operating characteristic roc analysis also highlighted let7f5p mir3383p potential robustness plasma biomarkers diagnosis potential therapeutic targets sals diseasepmid35082326 doi101038 s41598022050674,0.0
smoothened#x2f ampactivated protein kinase signaling oligodendroglial cell maturation front cell neurosci 2022 jan 10 15801704 doi 103389 fncel2021801704 ecollection 2021abstractthe regeneration myelin known restore axonal conduction velocity demyelinating event remyelination failure central nervous system contributes severity progression demyelinating diseases multiple sclerosis remyelination controlled many signaling pathways sonic hedgehog shh pathway shown canonical activation key effector smoothened smo increases proliferation oligodendrocyte precursor cells via upregulation transcription factor gli1 hand inhibition gli1 also found promote recruitment subset adult neural stem cells subsequent differentiation oligodendrocytes since smo also able transduce shh signals via various noncanonical pathways blockade gli1 addressed potential noncanonical smo signaling contribute oligodendroglial cell maturation myelinating cells using noncanonical smo agonist gsa10 downregulates gli1 using olineum cell line show gsa10 promotes gli2 upregulation mbp mal opalin expression via smo ampactivated protein kinase ampk signaling efficiently increases number axonal contact ensheathment oligodendroglial cell moreover gsa10 promotes recruitment differentiation oligodendroglial progenitors demyelinated corpus callosum vivo altogether data indicate noncanonical signaling involving smo ampk modulation gli1 downregulation promotes oligodendroglia maturation axon engagement thus gsa10 activation signaling pathway represents novel potential remyelinating agentpmid35082605 pmcpmc8784884 doi103389 fncel2021801704,1.0
characteristics peerbased interventions individuals neurological conditions scoping review disabil rehabil 2022 jan 27132 doi 101080 0963828820222028911 online ahead printabstractpurpose peerbased interventions increasingly popular costeffective therapeutic opportunities support others experiencing similar life circumstances however little known similarities differences among peerbased interventions outcomes people neurological conditions scoping review aims describe compare characteristics existing peerbased interventions adults common neurological conditionsmaterials methods searched medline cinahl psychinfo embase research peerbased interventions individuals brain injury parkinsons multiple sclerosis spinal cord injury stroke june 2019 search updated march 2021 fiftythree 2472 articles found includedresults characteristics peerbased intervention population vary significantly include individual groupbased formats delivered inperson telephone online content varied structured education tailored approaches participant outcomes included improved health confidence selfmanagement skills however varied based intervention modelconclusion various peerbased interventions exist definition means peer research using rigorous methodology needed determine effective interventions clear definitions program component needed better understand outcomes mechanism action within interventionimplications rehabilitationrehabilitation services can draw various peer support interventions add experiential knowledge support based shared experience enhance outcomesfulfilling role peer mentor may beneficial encouraged part rehabilitation process people sci tbi stroke pd msin planning peerbased interventions tbi stroke sci pd ms populations important clearly define intervention components evaluate outcomes measure impact interventionpmid35085058 doi101080 0963828820222028911,0.0
epsteinbarr virus neurological diseases front mol biosci 2022 jan 10 8816098 doi 103389 fmolb2021816098 ecollection 2021abstractepsteinbarr virus ebv also known human herpesvirus 4 doublestranded dna virus ubiquitous 9095 population gamma herpesvirus exists two main states latent infection lytic replication encoding viral proteins different functions human blymphocytes epithelial cells ebvsusceptible host cells ebv latently infects b cells nasopharyngeal epithelial cells throughout life immunologically active individuals ebvinfected cells free viruses gene products abnormally elevated ebv titers observed cerebrospinal fluid studies shown ebv can infect neurons directly indirectly via infected blymphocytes induce neuroinflammation demyelination promote proliferation degeneration necrosis glial cells promote proliferative disorders b tlymphocytes contribute occurrence development nervous system diseases alzheimers disease parkinsons disease multiple sclerosis acute cerebellar ataxia meningitis acute disseminated encephalomyelitis brain tumors however specific underlying molecular mechanisms unclear paper review mechanisms underlying role ebv development central nervous system diseases bebeneficial providing new research ideas potential clinical therapeutic targets neurological diseasespmid35083281 pmcpmc8784775 doi103389 fmolb2021816098,1.0
natalizumab concentrations pregnancy three patients multiple sclerosis clinical commentary mult scler 2022 feb 28 2 326327 doi 101177 13524585211069922no abstractpmid35083940 doi101177 13524585211069922,0.0
effectiveness zonisamide childhood refractory epilepsy childs nerv syst 2022 jan 27 doi 101007 s0038102205458y online ahead printabstractintroduction zonisamide zns new generation antiepileptic drug aed used refractory epilepsy study assessed effectiveness reliability zns childhood refractory epilepsymethod sixtyeight epilepsy patients followed paediatric neurology clinic 2013 2019 addon therapy zns added seizures continued despite multiple drugs used included retrospective study demographic findings seizure aetiology pretreatment posttreatment electroencephalography findings treatment responses side effects drugs given assessed patientsresults 46 676 patients refractory generalized epilepsy rge group using multiple aeds 22 3235 patients refractory focal epilepsy rfe group patients 12 1765 followed idiopathic epilepsy 8 1176 followed epilepsy unknown aetiology twentytwo 3236 patients followed structural abnormality 8 patients 1177 followed genetic disease 4 patients 588 followed infectious sequel 14 patients 2059 followed metabolic reasons rge group 50 reduction found seizures 26 565 patients seizures 7 152 patients found terminated completely rfe group 50 reduction found seizures 19 864 patients seizures 2 91 patients found terminated completely termination 50 reduction seizures 4 6 patients followed diagnosis tuberous sclerosis complex tsc significantconclusion zns effective reliable option addon therapy paediatric refractory epilepsy especially focal epilepsy can also considered treatment tsc patientspmid35083515 doi101007 s0038102205458y,0.0
can cystinuria decrease effectiveness rirs highpower hoyag laser children outcomes tertiary endourology referral center urolithiasis 2022 jan 27 doi 101007 s0024002201301w online ahead printabstractcystinuria cause cystine urolithiasis accounts 26 urinary stones children low prevalence high recurrence rate making metabolic disorder therapeutic challenge pediatric population aim work evaluate efficacy safety retrograde intrarenal surgery rirs pediatric patients cystinuria kidney stones smaller 2 cm prospective study 64 stones treated 22 retrograde intrarenal surgeries rirs cystinuric pediatric patients renal proximal ureteral stones less 2 cm average age 95 years following data analyzed demographics stone characteristics surgical data intra postoperative complications location stones 687 calyces 203 renal pelvis 93 ureteropelvic junction 41 cases multiple locations average cystinuria level procedure 825 mg dl anatomy 73 interventions increased difficulty flexible ureteroscopy decreased stone free rates distorted renal anatomy present sclerosis pelvis infundibulum abnormal calyceal dilations excluded calyces intraoperative complications occurred 182 procedures renovesical ultrasound performed patients first postoperative month sfr 59 cystinuric patients challenge pediatric urologists decreasing effectiveness rirs however better treatment swl fewer complications pcnl pediatric population diseasepmid35084538 doi101007 s0024002201301w,0.0
intrinsic bloodbrain barrier dysfunction contributes multiple sclerosis pathogenesis brain 2022 jan 27awac019 doi 101093 brain awac019 online ahead printabstractbloodbrain barrier bbb breakdown immune cell infiltration central nervous system cns early hallmarks multiple sclerosis ms mechanisms leading bbb dysfunction incompletely understood generally thought consequence neuroinflammation challenged view asked intrinsic alterations bbb ms patients contribute ms pathogenesis end made use human induced pluripotent stem cells hipscs derived healthy controls hc ms patients differentiated brain microvascular endothelial cell bmec like cells vitro model bbb msderived bmeclike cells showed impaired junctional integrity barrier properties efflux pump activity compared hc also msderived bmeclike cells displayed inflammatory phenotype increased adhesion molecule expression immune cell interactions activation wnt catenin signaling msderived endothelial progenitor cells enhanced barrier characteristics reduced inflammatory phenotype study provides evidence intrinsic impairment bbb function ms patients can modeled vitro human ipscderived bmeclike cells thus suitable explore molecular underpinnings bbb dysfunction ms will assist identification potential novel therapeutic targets bbb stabilizationpmid35085379 doi101093 brain awac019,0.0
development indicator smoking status people multiple sclerosis administrative data mult scler j exp transl clin 2022 jan 21 8 1 20552173221074296 doi 101177 20552173221074296 ecollection 2022 janmarabstractbackground administrative data lack health behavior informationmethods developed administrative case definition past current ever smoking 1320 individuals ms manitoba canada candidate indicators ever smoked included smoking cessation medications diagnosis codes tobacco use chronic obstructive pulmonary disease using variable lookback periodsresults compared selfreported smoking status case definition incorporating indicators lifetime lookback period sensitivity 3198 positive predictive value 7826conclusion smoking status definition partially control confounding due smoking low sensitivitypmid35083062 pmcpmc8785308 doi101177 20552173221074296,0.0
ginsenosides central nervous system diseases pharmacological actions mechanisms therapeutics phytother res 2022 jan 27 doi 101002 ptr7395 online ahead printabstractthe nervous system one complex physiological systems central nervous system diseases cnsds serious diseases affect human health ginseng panax l root panax species famous chinese herbs used various diseases china japan korea since ancient times remain popular natural medicine used worldwide modern times ginsenosides main active components ginseng increasing evidence demonstrated ginsenosides can prevent cnsds including neurodegenerative diseases memory cognitive impairment cerebral ischemia injury depression brain glioma multiple sclerosis confirmed numerous studies therefore review summarizes potential pathways ginsenosides affect pathogenesis cnsds mainly including antioxidant effects antiinflammatory effects antiapoptotic effects nerve protection provides novel ideas treatment cnsdspmid35084783 doi101002 ptr7395,0.0
automatic deep learning multicontrast corpus callosum segmentation multiple sclerosis j neuroimaging 2022 jan 26 doi 101111 jon12972 online ahead printabstractbackground purpose corpus callosum cc atrophy predictive future disability multiple sclerosis ms however current segmentation methods either labor computationally intensive therefore developed automated deep learningbased cc segmentation tool hypothesized output correlate disabilitymethods cohort 631 ms patients 449 females baseline age 41 11 years 3dimensional t1weighted t2weighted fluidattenuated inversion recovery flair mri used development data 204 patients manually segmented train convolutional neural networks extracting midsagittal intracranial cc areas remaining data used compare segmentations freesurfer benchmark outputs regard clinical correlations 15 3 tesla reproducibility cohort 9 ms patients evaluated segmentation robustnessresults deep learningbased tool accurate selecting appropriate slice segmentation 98 accuracy within 3 mm manual ground truth segmenting cc dice coefficient 8891 intracranial areas 9798 accuracy lower higher atrophy reproducibility excellent intraclass correlation coefficient 90 t1weighted scans moderategood flair 7475 segmentations associated baseline future average followup time 67 years expanded disability status scale 13 24 symbol digit modalities test r 1829 scoresconclusions present fully automatic deep learningbased cc segmentation tool optimized modern imaging ms clinical correlations par computationally expensive alternativespmid35083815 doi101111 jon12972,0.0
pelvic floor muscle training multiple sclerosis patients lower urinary tract dysfunction systematic review metaanalysis abstractbackground pelvic floor muscle training pfmt conservative treatment programme management lower urinary tract dysfunction lutd systematic review aimed investigate overall effectiveness pfmt lutd people multiple sclerosis ms methods seven databases pubmed medline scopus pedro wos cinahl cochrane embase searched 1990 july 2019 investigated urine leakage primary outcome secondary outcomes neurogenic bladder symptoms measured overactive bladder questionnaire oabv8 questionnaire power endurance pelvic floor musclesresults fifteen studies identified eligible urine leakage standardised mean difference smd 050 95 ci 078 023 neurogenic bladder symptoms smd224 95 ci 444 003 significantly decreased pfmt people ms pfmt increased overall endurance power pelvic floor muscles moderately significantly smd125 95 ci 069 181 smd064 95 ci 024 105 respectivelyconclusions moderate highquality studies showed overall efficacy pfmt decreasing urine leakage neurogenic bladder symptoms increasing endurance power pelvic floor muscles ms patients lower urinary tract symptoms benefit pfmt short term,0.0
evidence telomere attrition potential role dna damage systemic sclerosis background investigate role cell senescence systemic sclerosis ssc analyzed telomere shortening ts ssc patients effect targeting dna damage bleomycin model skin fibrosisresultstelomere length tl blood leukocytes 174 ssc patients 68 healthy controls measured southern blot found shorter agestandardized tl ssc patients compared healthy controls tl shorter ssc patients ild compared without ild antitopoisomerase positive compared anticentromere positive patients analyze potential role dna damage skin fibrosis evaluated effects dna protective gse4 peptide bleomycin mouse model scleroderma fibrotic response cultured human dermal fibroblasts administration gse4nanoparticles attenuated bleomycininduced skin fibrosis measured massons staining collagen reduced acta2 ctgf mrna expression whereas transduction dermal fibroblasts lentiviral gse4 expression vector reduced col1a1 acta2 ctgf gene expression stimulation bleomycin tgf parallel reduction phosphohistone h2ax marker dna damageconclusionsssc associated ts particularly patients lung disease antitopoisomerase antibodies administration gse4 peptide attenuated experimental skin fibrosis reduced fibroblast expression profibrotic factors supporting role oxidative dna damage scleroderma,0.0
ebv cause multiple sclerosis available,0.0
medical cannabis use canadians multiple sclerosis abstractbackground extent medical cannabis use people multiple sclerosis ms canada evaluated decade since recreational cannabis legalized legalization provided avenue legal cannabis previously inaccessible access alternative therapy objective evaluate prevalence medical cannabis use canadians ms reasons used adverse effects well context surrounding obtained users learned itmethods anonymous questionnaire distributed prospective participants various channels questionnaire included questions participant characteristics quality life ms medical cannabis use also employed two validated patientreported outcome measures pdds msqol54results completed questionnaires submitted 344 individuals among respondents 215 344 645 reported used medical cannabis least 180 523 reported still currently using based disease quality life data found respondents severe progressive forms ms likely tried medical cannabis medical cannabis used current former users treat sleep problems 842 pain 800 spasticity 684 reported adverse effects drowsiness 572 feeling quiet subdued 488 difficulty concentrating 284 current former users obtained cannabis legal reliable source 761 many 74 learned medical cannabis someone healthcare providerconclusions study showed nearly twothirds survey respondents comprised canadians living ms tried medical cannabis least greater disease burden likely tried users reported cannabis moderately highly effective treating several symptoms adverse effects generally severe main factor driving medical cannabis cessation results support need research examining medical cannabis use ms evidencebased resources publicly available exploring potential therapy,0.0
ononin ameliorates inflammation cartilage degradation rat chondrocytes il1induced osteoarthritis downregulating mapk nfb pathways background osteoarthritis oa treatment aims improve inflammation delay cartilage degeneration however effective strategy presently available ononin representative isoflavone glycoside component extracted natural chinese herbs exerts antiinflammatory proliferative effects however therapeutic effect ononin chondrocyte inflammation remains unclearmethodsin study explored therapeutic effect potential mechanism ononin oa establishing interleukin1 beta il1 induced chondrocyte inflammation modelresultsour results verified ononin alleviated il1induced decrease chondrocyte viability attenuated overexpression inflammatory factors tumour necrosis factor tnf interleukin 6 il6 simultaneously inhibited expression cartilage extracellular matrix ecm degrading enzymes matrix metalloproteinase13 mmp13 furthermore decomposition collagen ii protein alleviated oa model ononin finally ononin improved chondrocyte inflammation downregulating mitogenactivated protein kinase mapk nuclear factor kappab nfb signalling pathwaysconclusionour findings suggested ononin inhibit il1induced proinflammatory response ecm degradation chondrocytes interfering abnormal activation mapk nfb pathways indicating protective effect oa,0.0
progressive multifocal leukoencephalopathy patient mediastinal teratoma case report background progressive multifocal leukoencephalopathy pml rare demyelinating lytic brain infection caused john cunningham virus jcv jcv manifests primarily patients innate immunodeficiency taking immunomodulatory medications case study report pml patient comorbid mediastinal teratoma mild lymphopeniacase presentationa 73yearold female presented 3month history progressive hemiplegia hemianopsia cognitive impairment diagnosed pml cerebrospinal fluid metagenomics sequencing brain biopsy extensive immunological tests reveal apparent immunodeficiency workup revealed pml likely first presentation mediastinal teratoma mild lymphopenia mirtazapine immunoglobulin started patients condition relatively stable approved discharged hospital unfortunately died lung infection 10 months first presentationconclusionsthis case confirms mediastinal teratoma may induce lymphopenia trigger pml delayed incorrect diagnosis may worsen course disease result poor prognosis,1.0
vision prognosis associated factors optic neuritis dependence glial autoimmune antibodies j ophthalmol 2022 jan 23s00029394 22 000162 doi 101016 jajo202201015 online ahead printabstractpurpose assess visual prognosis optic neuritis dependence glial autoimmune antibody status associated factorsdesign longitudinal observational cohort study methods patients measurements serum concentrations glial autoantibodies consecutively longitudinally examined minimal followup three months patients multiple sclerosis double seronegative results excludedresults study included 529 patients aquaporin4 immunoglobulin aqp4igg seropositive n291 myelin oligodendrocyte glycoprotein immunoglobulin mogigg seropositive n112 doubleseronegative n126 1022 episodes aqp4igg seropositive n550 mogigg seropositive n254 doubleseronegative n218 prevalence severe vision loss bestcorrected visual acuity bcva 20 200 end followup higher p0001 aqp4igg group 236 550 429 seronegative group 68 218 312 mogigg group 15 254 59 prevalence good vision recovery bcva20 40 higher p0001 mogigg group 229 254 902 seronegative group 111 218509 aqp4igg group 236 550 429 multivariable logistic analysis higher prevalence severe vision loss associated aqp4igg seropositivity odds ratio 166 95 confidence interval ci 114 243 p0008 male sex or197 95ci133 293 p0001 age onset 45 years or193 95ci135 277 p0001 nadir vision 20 200 or1411 95ci654 3693 p0001 higher number recurrences or135 95ci114 161 p0001 higher prevalence good vision outcome associated mogigg seropositivity or813 95ci482 142 p0001 age onset 18 years or178 95ci118 271 p0006 nadir visual acuity 20 40 or403 95ci145 1437 p0015 lower number recurrences or060 95ci050 072 p0001 conclusion severe vision loss prevalence aqp4igg group mogigg group seronegative group429 59 312 respectively associated aqp4igg seropositivity male gender older age onset worse nadir vision higher number recurrencespmid35081416 doi101016 jajo202201015,1.0
severe lateonset neutropenia induced ocrelizumab multiple sclerosis patient case report clin case rep 2022 jan 19 10 1 e05299 doi 101002 ccr35299 ecollection 2022 janabstractocrelizumab recombinant humanized antibody targeted cd20 molecule approved treatment relapsing primary progressive multiple sclerosis common adverse events ocrelizumab include infusionrelated reactions like rash pruritus flushing lateonset neutropenia lon rarely reported complication ocrelizumab therapy report case severe lateonset neutropenia patient primary progressive multiple sclerosis treated ocrelizumab neutropenia occurring 3 months last dose received treated empirical broadspectrum intravenous antibiotics filgrastim severe lateonset neutropenia rare unpredictable adverse event outlines importance regular routine blood workup detecting severe neutropenia early coursepmid35079395 pmcpmc8770231 doi101002 ccr35299,0.0
communication coordination security people multiple sclerosis cocosms randomised phase ii clinical trial protocol bmj open 2022 jan 25 12 1 e049300 doi 101136 bmjopen2021049300abstractintroduction patients multiple sclerosis ms complex needs range organising ones everyday life measures diseasespecific therapy monitoring palliative care patients ms likely depend multiple healthcare providers various authorities often difficult coordinate thus will probably benefit comprehensive crosssectoral coordination services provided care case management ccm though studies shown case management improves quality life qol functional status reduces service use benefits yet investigated severely affected patients ms explorative phase ll clinical trial evaluated ccm longterm crosssectoral outreaching services addition considered unit care patients caregivers methods analysis eighty patients ms caregivers will randomly assigned either control standard care intervention group standard care plus ccm 12 months regular data assessments will done baseline 3month intervals primary outcome will evaluate patients qol secondary outcomes patients treatmentrelated risk perception palliative care needs anxiety depression use healthcare services caregivers burden qol meeting patients caregivers needs evaluating ccm intervention will also evaluate ccm individual interviews focus groups sample size calculation based standardised effect 05 one baseline four followup assessments correlation 05 linear mixed models repeated measures will applied analyse changes quantitative outcomes time multiple imputation approaches taken assess robustness results explorative approach phase ll clinical trial embedded qualitative research will allow development final design confirmative phase lll trialethics dissemination trial will conducted declaration helsinki approved ethics commission cologne universitys faculty medicine trial results will published openaccess scientific journal presented conferencestrial registration number german register clinical studies drks drks00022771 pmid35078833 doi101136 bmjopen2021049300,0.0
oligodendrocytes myelin active players neurodegenerative brains dev neurobiol 2022 jan 26 doi 101002 dneu22867 online ahead printabstractoligodendrocytes ols major type glial cells central nervous system generate multiple myelin sheaths wrap axons myelin ensures fast efficient propagation action potentials along axons supports neurons nourishment decay ols myelin implicated agerelated neurodegenerative diseases changes generally considered inevitable result neuron loss axon degeneration noticeably ols myelin undergo dynamic changes healthy adult brains newly formed ols continuously added throughout life differentiation oligodendrocyte precursor cells opcs preexisting myelin sheaths may undergo degeneration remodeling increasing evidence shown changes ols myelin present early stages neurodegenerative diseases even prior significant neuronal loss functional deficits importantly oligodendrogliaspecific manipulation either deletion disease gene enhancement myelin renewal can alleviate functional impairments neurodegenerative animal models findings underscore possibility ols myelin passively actively involved neurodegenerative diseases may play important role modulating neuronal function survival review summarize recent work characterizing ol myelin changes healthy neurodegenerative brains discuss potential targeting oligodendroglial cells treating neurodegenerative diseases article protected copyright rights reservedpmid35081276 doi101002 dneu22867,1.0
citrullination pathology inflammatory autoimmune disorders recent advances future perspectives cell mol life sci 2022 jan 25 79 2 94 doi 101007 s00018022041263abstractnumerous posttranslational modifications ptms govern collective metabolism cell altering structure functions proteins action prevalent ptms encompassing phosphorylation methylation acylations ubiquitination glycosylation well documented less explored protein ptm conversion peptidylarginine citrulline subject review process citrullination catalysed peptidylarginine deiminases pads family conserved enzymes expressed variety human tissues accumulating evidence suggest citrullination plays significant role regulating cellular metabolism gene expression affecting multitude pathways modulating chromatin status will discuss biochemical nature arginine citrullination enzymatic machinery behind also provide information pathological consequences citrullination development inflammatory diseases rheumatoid arthritis multiple sclerosis psoriasis systemic lupus erythematosus periodontitis covid19 cancer thromboembolism finally developments inhibitors protein citrullination recent clinical trials providing promising therapeutic approach inflammatory disease targeting citrullination discussedpmid35079870 doi101007 s00018022041263,0.0
patient activation association symptom burden quality life across spectrum chronic kidney disease stages england background knowledge skills confidence manage ones health termed patient activation can assessed using patient activation measure pam measure increasingly recommended use chronic kidney disease ckd need better understand patient activation within population work aimed explore association pam patientreported outcomes namely symptom burden healthrelated quality life hrqol understand relationship patient activation outcomes importance people ckdmethodsnondialysis dialysis kidney transplant patients 14 renal units across england completed survey comprising questionnaires assessing patient activation symptom burden hrqollatent class analysis lca used determine hrqol symptom burden subgroups data multinomial logistic regression analyses performed investigate associations patient activation symptom burden hrqol classes separately adjusting age gender ethnicity deprivation treatment modalityresultsthree thousand thirteen participants mean age 615 years 618 males 47 haemodialysis included analysis patient activation strongly associated hrqol symptom burden classes identified highly activated patients likely report higher hrqol p 00001 292 95 ci 195439 fewer symptoms p 00001 259 95 ci 168402 conclusionlower activation levels associated higher symptom burden reduced hrqol across trajectory ckd stages treatment modalities therefore targeted holistic selfmanagement support focussing improving activation may potential improve aspects health experience valued individuals living kidney disease,0.0
novel disease specific scale characterize symptoms impacts fatigue us adults relapsing multiple sclerosis realworld study abstractbackground fatigue among frequent disabling symptoms patients relapsing multiple sclerosis rms objective measure ms fatigue impact daily life realworld us population using msspecific patientreported outcome pro instrument fatigue symptoms impacts questionnairerms fsiqrms methods ongoing prospective study recruited rms patients online patient community carenity across us baseline assessment data reported participants completed questionnaires including 20item fsiqrms questionnaire first seven symptomrelated items collected daily seven days 13 items seventh day assessing impacts fatigue fsiqrms scores range 0100 higher scoregreater severity impact fatigue several aspects patientsnull lives rated 0 impact 10 high impact data disease history disease status sleep social emotional functioning also captured baseline assessment data 300 rms patients reported followup assessments 18 months plannedresults 300 rms participants completed 7day assessment mean age 430 years 88 women fatigue rated severe mean score 573 fsiqrms symptom domain 3 impact subdomain scores 423 434 501 physical cognitive emotional coping participants relapse 78 reported less severe fatigue relapse 22 meansd symptom score 546178 vs 670197 p0001 fatigue higher intensity among depression without 49 vs 51 meansd symptom score 628169 vs 521193 p0001 among sleep disorder without 27 vs 73 612192 vs559186 p005 common factor associated increased fatigue heat exposure 82 participants 52 reported experiencing fatigue ms diagnosisconclusion fatigue influences daily functioning patients rms fsiqrms novel msspecific pro measure can advance understanding management fatigue,0.0
effect different initial rituximab regimens b cell depletion children autoimmune neurological diseases abstractbackgroundrituximab rtx promising bcelldepleting monoclonal antibody used treat several autoimmune neurological diseases children rtx administration regimen relies reconstitution b cells peripheral bloodobjectivethe objective study investigate effect different initial rtx regimens b cell depletionmethodsthis singlecenter retrospective analysis included children autoimmune neurological diseases received rtx group 1 received two infusions 375 mg m2 rtx group 2 received four infusions dose examined evolution b cells regular intervals patients time required b cell reconstitution risk factors effect immunoglobulin ig t cells studiedresultsa total 113 patients first course rituximab included median time required b cell reconstitution 1477 13011652 1819 16521986 days group 1 2 respectively p0008 ig production affected rtx reduced igg iga igm serum concentrations yet within normal level significant difference decline igg two groups absolute cell counts t cells change time treatment variation trend similar two groupsconclusionthe initial regimen rtx impacts time required b cell reconstitution increased time b cell reconstitution four standard infusions rtx compared two standard infusions furthermore prolonged b cell depletion leads decreased antibody production regular measurements serum ig concentrations rtx treatment followup performed regularly,0.0
effective rehabilitation interventions participation among people multiple sclerosis overview reviewsselect background multiple sclerosis ms common cause nontraumatic disability people aged 10 65 years evidence exists effectiveness multidisciplinary rehabilitation exercise however effectiveness rehabilitation approaches ms needs evaluation objective aimed systematically synthesize evaluate knowledge effectiveness rehabilitation interventions determinants participation among people ms pwms inform clinical guidelines rehabilitation methods joanna briggs institute methodology used pubmed embase cinahl psycinfo web science searched reviews systematic reviews metaanalyses metasyntheses published 2009 2019 types rehabilitation interventions provided pwms time settings eligible two reviewers independently screened extracted data recently published reviews mixed specific modalities included findings reported narrative summary mixedmethods analysis results among 108 eligible reviews 6 qualitative mixedmethods reviews 66 quantitative reviews included total pwms 90 000 overview provides solid evidence effectiveness spectrum modalities among modalities strong evidence effectiveness multidisciplinary cognitive exercise approaches physiotherapy occupational therapy including full body training functioning participation outcomes employment significantly affected quality life thus vocational rehabilitation initiated early healthcare professionals identify personal factors including relations coping rehabilitation process involve partners close family conclusions mixedmethods analysis revealed insufficient consensus perspectives pwms rehabilitation reported effects indicating research target experiences pwms furthermore rehabilitation patientcentred focus complexity needs organised performed experienced multidisciplinary team evidencebased rehabilitation initiated early pwms diagnosed follow international guidelines database registration prospero id crd42020152422,0.0
discovery novel sphingosine1phosphate1 receptor agonists treatment multiple sclerosis j med chem 2022 jan 25 doi 101021 acsjmedchem1c01979 online ahead printabstractthe sphingosine1phosphate1 s1p1 receptor agonists great potential treatment multiple sclerosis ms can inhibit lymphocyte egress receptor internalization designed synthesized triazole isoxazoline derivatives discover novel s1p1 agonist ms treatment two scaffolds isoxazoline derivative determined excellent vitro efficacy druglike properties among compound 21l found superior druglike properties well excellent vitro efficacies ec50 703 nm arrestin recruitment ec50 118 nm internalization also confirmed 21l effectively inhibited lymphocyte egress peripheral lymphocyte count test significantly improved clinical score experimental autoimmune encephalitis ms mouse modelpmid35077170 doi101021 acsjmedchem1c01979,0.0
clinical utility trendelenburg test people multiple sclerosis physiother theory pract 2022 jan 2418 doi 101080 0959398520222030446 online ahead printabstractbackground clinical utility trendelenburg test remains unknown people multiple sclerosis ms objective measure 1 intrarater reliability 2 agreement goniometerassessed trendelenburg pelvisonfemur angle pof motion capture 3 concurrent validity trendelenburg pof hip abduction strength pof walking step negotiationmethods trendelenburg pof measured 20 people ms using goniometry motion analysis addition peak pof measured using motion analysis walking step ascent step descent intrarater reliability goniometerassessed trendelenburg pof agreement motion analysisassessed pof analyzed pearsons r used determine relationships trendelenburg pof hip abduction strength peak pof functional activityresults goniometerassessed trendelenburg pof demonstrated strong reliability icc 0948 strong agreement 3d motion analysis icc 0792 correlated moderately peak pof walking r 0519 step ascent r 0572 weakly step descent r 0463 hip abductor strength correlated weakly peak pof step ascent r 0307 negligibly walking r 0270 step descent r 0249 conclusions goniometerassessed trendelenburg pof reliable agreed motion analysis may provide insight hip abduction muscle performance functional activities people mspmid35073816 doi101080 0959398520222030446,0.0
movement disorders prog brain res 2022 268 1 379384 doi 101016 bspbr202110042 epub 2021 dec 14abstractover 30 years demonstrated gamma knife thalamotomy valuable method treating tremor parkinsons disease essential tremor also effective tremor associated multiple sclerosis date gamma knife pallidotomy received acceptance professionpmid35074091 doi101016 bspbr202110042,0.0
trigeminal neuralgia cranial pain syndromes prog brain res 2022 268 1 347378 doi 101016 bspbr202110041 epub 2022 jan 13abstractspontaneous trigeminal neuralgia painful condition face may require interventional treatment medicines fail control pain include microvascular decompression mvd gkns former moderately effective gkns become accepted alternative mvd adjunct like treatments condition successful majority patients means repeat treatments possible trigeminal neuralgia secondary conditions response gkns different avms dural arteriovenous fistulae epidermoids dose treat visible lesion usually cures neuralgia meningiomas necessary treat neuralgia separate entity neuralgia dose focused nerve gkns improve rare neuralgia associated vestibular schwannomas works multiple sclerosis well spontaneous illness evidence gkns can useful rare glossopharyngeal sphenopalatine neuralgiaspmid35074090 doi101016 bspbr202110041,0.0
identification genetic risk loci prioritization genes pathways myasthenia gravis genomewide association study proc natl acad sci u s 2022 feb 1 119 5 e2108672119 doi 101073 pnas2108672119abstractmyasthenia gravis chronic autoimmune disease characterized autoantibodymediated interference signal transmission across neuromuscular junction performed genomewide association study gwas involving 1 873 patients diagnosed acetylcholine receptor antibodypositive myasthenia gravis 36 370 healthy individuals identify diseaseassociated genetic risk loci replication discovered loci attempted independent cohort uk biobank also performed transcriptomewide association study twas using expression data skeletal muscle whole blood tibial nerve test effects diseaseassociated polymorphisms gene expression discovered two signals genes encoding acetylcholine receptor subunits common antigenic target autoantibodies gwas signal within cholinergic receptor nicotinic alpha 1 subunit chrna1 gene twas association cholinergic receptor nicotinic beta 1 subunit chrnb1 gene normal skeletal muscle two loci discovered 10p14 11q21 previous association signals ptpn22 hladqa1 hlab tnfrsf11a confirmed subgroup analyses demonstrate early lateonset cases different genetic risk factors genetic correlation analysis confirmed genetic link myasthenia gravis autoimmune diseases hypothyroidism rheumatoid arthritis multiple sclerosis type 1 diabetes finally applied priority index analysis identify potentially druggable genes proteins pathways study provides insight genetic architecture underlying myasthenia gravis demonstrates genetic factors within loci encoding acetylcholine receptor subunits contribute pathogenesispmid35074870 doi101073 pnas2108672119,0.0
epidemiological investigation multiple sclerosis related medical utilisation taiwan mult scler 2022 jan 2513524585211061341 doi 101177 13524585211061341 online ahead printabstractbackground increasing trend prevalence multiple sclerosis ms neglected longterm epidemiological investigations ms patients registered taiwan scarceobjective aim study investigate epidemiology ms medical utilisation among ms patients taiwanmethods national health insurance research database used source research population time period investigated 20012015 descriptive statistical analysis number ms patients conducted newly diagnosed ms patients frequencies emergency visits hospitalisations changes temporal distributions calculatedresults standardised incidence ms peaked 050 100 000 2003 highest standardised prevalence 714 100 000 2015 highest standardised mortality 011 100 000 2015 overall mortality rate 1334 1000 personyears number annual emergency visits ms patients peaked 09 35 2011 longest annual length hospital stays 192 401 days 2001 decreased 56 235 days 2015conclusion standardised prevalence ms steadily increased incidence slightly decreased 2001 2015pmid35076314 doi101177 13524585211061341,0.0
teriflunomide reduced lesions pediatric multiple sclerosis jama 2022 jan 25 327 4 314 doi 101001 jama202125109no abstractpmid35076668 doi101001 jama202125109,1.0
impact covid19 lockdown progressive multiple sclerosis patients neurol sci 2022 jan 24 doi 101007 s1007202205909z online ahead printabstractintroduction covid19 pandemic caused major changes lifestyle access health services worldwide progressive multiple sclerosis pms patients vulnerable population high risk disability worseningobjective methods objective study assess health outcomes covid19 lockdown cohort 225 pms patientsresults worsening neurological disability 197 fatigue 324 depression 304 weight increase 283 observed pms patients lockdown along discontinuation regular physical exercise 471 physical therapy 593 conclusion results highlight adverse impact pms patients public health measures implemented containment pandemicpmid35075574 doi101007 s1007202205909z,0.0
successful use infliximab refractory genital ulceration patient multiple sclerosis behcet disease j clin rheumatol 2021 dec 1 27 8s s880s882 doi 101097 rhu0000000000000659no abstractpmid35073644 doi101097 rhu0000000000000659,0.0
modulation pacemaker channel function model thalamocortical hyperexcitability demyelination cytokines cereb cortex 2022 jan 25bhab491 doi 101093 cercor bhab491 online ahead printabstracta consensus yet reached regarding exact prevalence epileptic seizures epilepsy multiple sclerosis ms addition underlying pathophysiological basis reciprocal interaction among neuroinflammation demyelination epilepsy remains unclear therefore better understanding cellular network mechanisms linking pathologies needed cuprizoneinduced general demyelination rodents valuable model studying ms pathologies studied relationship among epileptic activity loss myelin proinflammatory cytokines inducing acute generalized demyelination genetic mouse model human absence epilepsy c3h hej mice cellular network mechanisms studied using vivo vitro electrophysiological techniques found acute generalized demyelination c3h hej mice resulted lower number spikewave discharges increased cortical theta oscillations reduction slow rhythmic intrathalamic burst activity addition generalized demyelination resulted significant reduction amplitude hyperpolarizationactivated inward current ih thalamic relay cells accompanied lower surface expression hyperpolarizationactivated cyclic nucleotidegated channels phosphorylated form trip8b ps237trip8b suggest demyelinationrelated changes thalamic ih may one factors defining prevalence seizures mspmid35076711 doi101093 cercor bhab491,1.0
correction reliability televisits patients mild relapsingremitting multiple sclerosis covid19 era neurol sci 2022 jan 25 doi 101007 s10072022059053 online ahead printno abstractpmid35076808 doi101007 s10072022059053,0.0
advantages using optic nerve ecography predict clinical progression multiple sclerosis neurologia engl ed 2022 janfeb 37 1 73 doi 101016 jnrleng202107001no abstractpmid35074191 doi101016 jnrleng202107001,0.0
noncriteria manifestations primary antiphospholipid syndrome french multicenter retrospective cohort study background retrospective study aimed 1 describe prevalence characteristics noncriteria features primary antiphospholipid syndrome paps 2 determine prognostic valuemethodsthis retrospective french multicenter cohort study included patients diagnosed paps sydney criteria january 2012 january 2019 used kaplanmeier adjusted cox proportional hazards models compare incidence relapse paps without noncriteria manifestationsresultsone hundred seventynine patients paps included study time median age 5250 years 390 6525 mainly women n 112 626 among fortythree patients 240 presented least one noncriteria manifestation followup autoimmune cytopenias n 17 395 libman sachs endocarditis n 5 116 aps nephropathy n 4 93 livedo reticularis n 8 186 neurological manifestations n 12 279 comparison paps without noncriteria manifestations n 136 paps noncriteria features arterial thrombosis n 24 558 vs n 48 353 p 0027 frequent preeclampsia n 6 143 vs n 4 31 p 002 prevalence triple positivity significantly increased patients noncriteria features n 20 476 vs n 25 198 p 0001 patients paps noncriteria manifestations n 43 received significantly additional therapies combined vitamin k antagonists antiaggregants catastrophic aps caps tended frequent paps noncriteria features n 2 51 vs none p 0074 paps noncriteria manifestations significantly increased rates relapse n 20 588 vs 33 337 p 0018 bivariate analysis survival analyses hazard ratio hr relapse significantly different two groups hr 134 067 268 p 040 conclusionsthe presence noncriteria features important consider associated particular clinical laboratory profiles increased risk relapse need additional therapies prospective studies necessary better stratify prognosis management paps,0.0
situational analysis child adolescent mental health services systems western cape province south africa background even though child adolescent mental health global health priority services limited particularly low middleincome countries lmic therefore need comprehensive strengthening requires knowledge hardware elements system human resources financing medicines technology organisational structure service infrastructure information systems study sought examine elements child adolescent mental health camh services systems western cape province south africamethodsthe world health organization assessment instrument mental health systems whoaims version 22 2005 adapted identify key variables interest camh data collected calendar year 2016 focused public health sector outlined findings based best available data across six domains whoaimsresultsin domain 1 found provincial camh policy implementation plans support national camh policy unable identify camhspecific budget domain 2 dedicated provincial leadership structure camh dedicated child adolescentfriendly mental health services primary secondary care levels tertiary level three specialist camh teams majority camh resources based city cape town limited resources rural districts essential medicines available facilities majority children adolescents access free services domain 3 data limited extent training offered primary healthcare staff little psychosocial interventions available primary care domain 4 identified small variable camh workforce across levels care domain 5 public health campaigns focused camh little evidence formal intersectoral collaboration camh identified domain 6 identified significant limitations health information systems camh including lack child adolescentspecific disaggregated data establish baselines policy development monitoring evaluation camh researchconclusionsthis study identified significant structural weaknesses camh presents clear call action strengthen services systems province south africa important expand research also include provider user perspectives service strengthening,0.0
excitotoxicity calcium mitochondria triad synaptic neurodegeneration abstractglutamate commonly engaged neurotransmitter mammalian central nervous system acting mediate excitatory neurotransmission however high levels glutamatergic input elicit excitotoxicity contributing neuronal cell death following acute brain injuries stroke trauma excitotoxic cell death also implicated neurodegenerative disease models role acute apoptotic cell death remains controversial setting chronic neurodegeneration nevertheless clear excitatory synaptic dysregulation contributes neurodegeneration evidenced protective effects partial nmethyldaspartate receptor antagonists review evidence sublethal excitatory injuries relation neurodegeneration associated parkinsons disease alzheimers disease amyotrophic lateral sclerosis huntingtons disease contrast classic excitotoxicity emerging evidence implicates dysregulation mitochondrial calcium handling excitatory postsynaptic neurodegeneration discuss mechanisms regulate mitochondrial calcium uptake release impact lrrk2 pink1 parkin betaamyloid glucocerebrosidase mitochondrial calcium transporters role autophagic mitochondrial loss axodendritic shrinkage finally discuss strategies normalizing flux calcium mitochondrial matrix thereby preventing mitochondrial calcium toxicity excitotoxic dendritic loss mechanisms underlie increased uptake decreased release mitochondrial calcium vary different model systems common set strategies normalize mitochondrial calcium flux can prevent excitatory mitochondrial toxicity may neuroprotective multiple disease contexts,1.0
thoracic lymphadenopathies diffuse systemic sclerosis observational study 48 patients using computed tomography background thoracic multidetector computed tomography mdct essential detection interstitial lung disease ild patients systemic sclerosis ssc thoracic mdct assessment can reveal presence thoracic lymphadenopathies lap whose signification remains uncertain purpose study describe characteristics assess significance thoracic lap patients diffuse sscmethodswe conducted monocentric observational study adult patients diffuse ssc collected general patient first thoracic mdct characteristics petct outcome data comparisons made patients without thoracic lapresultsfortyeight patients included 30 patients 625 ild 23 48 least one thoracic lap first mdct assessment median number per patient thoracic lap 3 18 mean size 117 17 mm mainly located right paratracheal area 228 total number lap right hilar area 203 left hilar area 65 subcarinal area 152 petct showed lymph node hypermetabolism 11 15 patients 733 mean suvmax 4 13 significantly males p 0002 patients exposed silica p 0001 patients thoracic lap ild significantly extended according goh score p 003 using semiquantitative score mixed groundglass reticulation p 001 global abnormalities p 003 patients thoracic lap ild thirteen patients 271 died followup without significant difference according presence thoracic lap p 015 also significant difference concerning immunosuppressive treatment initiation p 017 conclusionsthoracic lap common diffuse ssc generally multiple bulky moderately hypermetabolic located base mediastinum lymph node chains presence correlates extent ild absence ild thoracic lap presence seems often explained silica exposuretrial registration na,0.0
mixed blessing ampk signaling cancer treatments background nutrient acquisition metabolism pathways altered cancer cells meet bioenergetic biosynthetic demands major regulator cellular metabolism energy homeostasis normal cancer cells ampactivated protein kinase ampk ampk influences cell growth via modulation mechanistic target rapamycin mtor pathway specifically inhibiting mtor complex mtorc1 facilitates cell proliferation activating mtorc2 cell survival given conflicting roles effects ampk activation cancer can counter intuitive prior establishment cancer ampk acts tumor suppressor however following onset cancer ampk shown either suppress promote cancer depending cell type statemethodsto unravel controversial roles ampk cancer developed computational model simulate effects pharmacological maneuvers target key metabolic signalling nodes specific focus ampk mtorc modulators specifically constructed ordinary differential equationbased mechanistic model ampkmtorc signaling parametrized model based existing experimental dataresultsmodel simulations conducted yield following predictions increasing ampk activity opposite effects mtorc depending nutrient availability ii indirect inhibition ampk activity inhibition sirtuin 1 sirt1 effect mtorc activity conditions low nutrient availability iii balance cell proliferation survival exhibits intricate dependence dep domaincontaining mtorinteracting protein deptor abundance ampk activity iv simultaneous direct inhibition mtorc2 activation ampk potential strategy suppressing cell survival proliferationconclusionstaken together model simulations clarify competing effects roles key metabolic signalling pathways tumorigenesis may yield insights innovative therapeutic strategies,0.0
impact cyba genotypes severity progression multiple sclerosis eur j neurol 2022 jan 24 doi 101111 ene15259 online ahead printabstractbackground nox2 enzyme myeloid cells generates reactive oxygen species ros implicated pathology multiple sclerosis ms aimed determine impact genetic variation within cyba encodes functional cyba p22phox subunit nox2 ms severity progressionmethods one hundred three ms patients 49 median 17 years followup time first ms diagnosis genotyped single nucleotide polymorphisms snp rs1049254 rs4673 within cyba results matched disease severity time diagnosis secondary progressive ms spms nox2mediated formation ros measured chemiluminescence blood myeloid cells healthy donors n55 defined genotypes rs1049254 rs4673results rs1049254 g rs4673 cyba alleles associated reduced formation ros thus defined lowros alleles patients carrying lowros alleles showed reduced multiple sclerosis severity score p002 n103 linear regression delayed onset spms p002 hr 046 n100 logrank test cohort examined 2005 patients carrying lowros cyba alleles showed 20 years longer time secondary progression p0003 hr 029 n59 logrank test conclusions results implicate nox2 ms particular development secondary progressive disease point towards nox2reductive therapy aiming delay secondary progressionpmid35073438 doi101111 ene15259,0.0
clonally expanded b cells multiple sclerosis bind ebv ebna1 glialcam multiple sclerosis ms heterogenous autoimmune disease autoreactive lymphocytes attack myelin sheath central nervous system b lymphocytes cerebrospinal fluid csf patients ms contribute inflammation secrete oligoclonal immunoglobulins1 2 epsteinbarr virus ebv infection epidemiologically linked ms pathological role remains unclear3 demonstrate highaffinity molecular mimicry ebv transcription factor ebv nuclear antigen 1 ebna1 central nervous system protein glial cell adhesion molecule glialcam provide structural vivo functional evidence relevance crossreactive csfderived antibody initially identified singlecell sequencing pairedchain b cell repertoire ms blood csf followed protein microarraybased testing recombinantly expressed csfderived antibodies msassociated viruses sequence analysis affinity measurements crystal structure ebna1peptide epitope complex autoreactive fab fragment enabled tracking development naive ebna1restricted antibody mature ebna1glialcam crossreactive antibody molecular mimicry facilitated posttranslational modification glialcam ebna1 immunization exacerbates disease mouse model ms antiebna1 antiglialcam antibodies prevalent patients ms results provide mechanistic link association ms ebv guide development new ms therapies,1.0
multiple sclerosis disease activity disability following discontinuation natalizumab pregnancy jama netw open 2022 jan 4 5 1 e2144750 doi 101001 jamanetworkopen202144750abstractimportance magnitude risk pregnancyrelated multiple sclerosis relapses particularly severe relapses following natalizumab cessation unclear whether risk reduced pregnancy modifiable factorsobjective determine association early natalizumab withdrawal pregnancy risk severe relapses relapserelated disabilitydesign setting participants prospective cohort study used data german multiple sclerosis pregnancy registry enrolled participants november 2006 february 2018 data collected structured telephoneadministered questionnaires review neurologists notes registry patients stopped natalizumab treatment within 2 years first trimester pregnancy included analysis data analyzed january november 2021exposures cessation natalizumab pregnancy first trimestermain outcomes measures severe significant relapserelated disability defined least 20point increase expanded disability status scale new worsening relapserelated ambulatory impairment multivariable models accounting measures disease severity repeated events usedresults cohort comprised 255 women 274 pregnancies mean sd age pregnancy onset 3125 427 years stopped natalizumab pregnancy n 85 median time last menstrual period 1429 weeks iqr 3144243 weeks first trimester n 189 pregnancy postpartum year relapses reported 183 pregnancies 6678 severe relapses 44 pregnancies 1605 potentially lifethreatening relapses 3 pregnancies 110 one year post partum significant relapserelated disability accrued 29 pregnancies 1058 relapses pregnancy n 109 3978 postpartum period n 135 4927 common pregnancy timedependent covariate associated reduced relapse risk adjusted hr 090 95 ci 064127 neither exclusive breastfeeding adjusted hr 134 95 ci 086210 restarting natalizumab within 4 weeks post partum adjusted hr 106 95 ci 048236 associated reduced risk early postpartum relapses 6 months delivery however relapse rate ratio 12 months post partum lower 049 95 ci 028086 natalizumab restarted first 4 weeks birthconclusions relevance cohort studys finding suggest 10 women may retain clinically meaningful disability pregnancyrelated natalizumab cessation relapses 1 year post partum information shared women natalizumab desire pregnancy weigh high risk pregnancyrelated relapses disability partly uncertain risks continuing natalizumab throughout pregnancy switching depleting agents conceptionpmid35072719 doi101001 jamanetworkopen202144750,0.0
systematic review socioeconomic consequences patients multiple sclerosis different levels disability cognitive function front neurol 2022 jan 6 12737211 doi 103389 fneur2021737211 ecollection 2021abstractmultiple sclerosis ms challenging disabling condition predominantly affecting individuals early adulthood ms affects physical cognitive mental health persons suffering disease well great impact financial status quality life however lack systematic approach toward assessing socioeconomic consequences ms objective systematically review analytical observational studies investigating socioeconomic consequences persons ms different levels physical disability cognitive function conducted systematic review socioeconomic consequences ms focus employment income work ability relationshiprelated outcomes persons ms special focus disability cognition additionally educational characteristics examined 4 957 studies identified 214 assessed eligibility total 19 studies included qualitative assessment 21 different outcomes identified identified studies reported higher unemployment higher early retirement higher risk unemployment relation higher physical disability also cognitive function found predictor employment unemployment studies pointed significant correlations greater disability lower earnings higher income benefits study found correlation relation cognitive function studies reported higher work disability relation higher physical disability lower cognitive function conclusion systematic review summarizes pronounced differences various socioeconomic outcomes patients ms regards physical disability cognitive function addition identified lack studies longitudinal design field can provide robust estimates covariate adjustments disease modifying treatmentspmid35069404 pmcpmc8770980 doi103389 fneur2021737211,0.0
oblique saccades internuclear ophthalmoplegia exp brain res 2022 jan 24 doi 101007 s00221021062836 online ahead printabstractoblique saccades often display component stretching shorter vector one cardinal direction slowed duration matches longer vector orthogonal direction resulting straighter trajectory internuclear ophthalmoplegia adducting saccades typically slowed vertical saccades unaffected known whether slowed adducting movements accompanied adaptive component stretching vertical vector oblique saccades crosssectional study recorded saccadic eye movement 5 patients right bilateral internuclear ophthalmoplegia multiple sclerosis 17 healthy controls using eyelink 1000 machine target stimulus located varying angles 0360 amplitudes 4 8 12 degrees saccade calculated curvature index main outcome measure area actual ideal straight trajectory oblique saccadic eye movements divided square length straight trajectory give unitless metric curvature 17 control subjects curvature showed strong positive correlation adducting saccades yoked abducting saccades eye internuclear ophthalmoplegia adducting saccades showed strong curvature concave horizontal meridian indicating inadequate component stretching abducting saccades differ controls new sign oblique saccadic curvature internuclear ophthalmoplegia indicates limitation range central adaptive changes response distal lesions affecting transmission saccadic commandpmid35067725 doi101007 s00221021062836,0.0
therapeutic potential combined therapy vitamin vitamin c experimental autoimmune encephalomyelitis eae lewis rats mol neurobiol 2022 jan 24 doi 101007 s12035022027550 online ahead printabstractdemyelination inflammation oxidative injury glial activation main pathological hallmarks multiple sclerosis ms vitamins essential micronutrients seem crucial pathogenesis ms particularly vitamins c found protective role ms development progression study therapeutic potential combined therapy vitamins c progression experimental autoimmune encephalomyelitis eae myelin repair mechanisms examined eae animal model ms induced female lewis rats rats treated daily intraperitoneal injections vitamins c combination found cosupplementation vitamins c mitigated neurological severity eae disease progression histological study confirmed significant reduction demyelination size inflammation immune cell infiltration well microglia astrocyte activation following coadministration vitamins c coadministration vitamins c also decreased levels proinflammatory cytokines tnf il1 inos increased gene expressions il10 nrf2 ho1 mbp combination therapy vitamins c also increased total antioxidant capacity decreased levels oxidative stress markers finally proved coadministration vitamins c antiapoptotic neuroprotective impacts eae via decreasing caspase3 increasing bdnf neun expressing cells present study suggests combined therapy vitamins c may effective strategy development alternative medicine boosting myelin repair demyelinating diseasespmid35072933 doi101007 s12035022027550,1.0
mechanistic biomarker studies demonstrate immune tolerance multiple sclerosis front immunol 2022 jan 5 12787498 doi 103389 fimmu2021787498 ecollection 2021abstractthe induction specific immunological tolerance represents important therapeutic goal multiple sclerosis autoimmune diseases sound knowledge target antigens underlying pathomechanisms disease presumed mechanisms action respective toleranceinducing approach essential successful translation furthermore suitable tools assays evaluate induction immune tolerance key aspects development treatments however investigation mechanisms action underlying tolerance induction poses several challenges optimization sensitive robust methods allow assessment low frequency autoreactive t cells longterm reduction change responses detection regulatory cell populations immune mediators well validation specific biomarkers indicating reduction inflammation damage needed develop toleranceinducing approaches successfully patients short review focuses demonstrate mechanistic proofofconcept antigenspecific toleranceinducing therapies mspmid35069562 pmcpmc8766750 doi103389 fimmu2021787498,0.0
transcriptional effects fingolimod treatment peripheral t cells relapsing remitting multiple sclerosis patients pharmacogenomics 2022 jan 24 doi 102217 pgs20210118 online ahead printabstractaim investigate transcriptional changes induced fingolimod fty t cells relapsing remitting multiple sclerosis patients patients methods transcriptomic changes 6 months fty therapy evaluated t cells 24 relapsing remitting multiple sclerosis patients rnasequencing followed technical validation pathway analysis results among differentially expressed genes cx3cr1 ccr7 resulted strongly downregulated respectively two relevant genes validated quantitative pcr largely confirmed findings two previous microarraybased studies similar design pathway analysis pointed involvement processes related immune function cell migration conclusion data support evidence fty induces major transcriptional changes genes involved immune response cell trafficking t lymphocytespmid35068175 doi102217 pgs20210118,0.0
using realworld accelerometryderived diurnal patterns physical activity evaluate disability multiple sclerosis j rehabil assist technol eng 2022 jan 12 920556683211067362 doi 101177 20556683211067362 ecollection 2022 jandecno abstractpmid35070348 pmcpmc8771734 doi101177 20556683211067362,0.0
dietary interventions improve health outcomes people multiple sclerosis cochrane review summary commentary neurorehabilitation 2022 jan 19 doi 103233 nre228000 online ahead printabstractbackground broad range complementary alternative medicine cam approaches including different dietary interventions alone conjunction conventional medicine currently trailed people multiple sclerosis ms published clinical experimental data suggest certain dietary interventions may improve msrelated health outcomesobjective assess effectiveness dietary interventions improve msrelated health outcomesmethods summarize updated cochrane review dietary interventions multiple sclerosisrelated outcomes conducted parks et al best available evidence discussed rehabilitation perspectiveresults overall 30 rcts 2335 participants evaluated range dietary interventions polyunsaturated fatty acids antioxidant supplements dietary programmes dietary supplements included trials one methodological issues leading unknown high risk bias findings suggest evidence uncertain effect dietary interventions msrelated health outcomesconclusions evidence dietary interventions people ms sparse uncertain robust studies neededpmid35068420 doi103233 nre228000,0.0
protocol assessment human tcell activation realtime metabolic flux analysis star protoc 2022 jan 11 3 1 101084 doi 101016 jxpro2021101084 ecollection 2022 mar 18abstractthe elevation glycolysis autoreactive t cells key target prevention treatment t cellrelated autoimmune diseases type 1 diabetes t1d describe simple efficient protocol isolating human peripheral blood mononuclear cells pbmcs t cells subsequent assessment t cell glycolysis using seahorse analyzer protocol useful analyze different subsets t cells applicable different autoimmune disease models ie t1d multiple sclerosis complete details use execution profile please refer kong et al 2021 pmid35072113 pmcpmc8761778 doi101016 jxpro2021101084,0.0
t1#x2f t2weighted ratio surrogate marker demyelination multiple sclerosis mult scler 2022 jan 2213524585211063622 doi 101177 13524585211063622 online ahead printno abstractpmid35067108 doi101177 13524585211063622,1.0
t1#x2f t2weighted ratio surrogate marker demyelination multiple sclerosisyes mult scler 2022 jan 2213524585211066313 doi 101177 13524585211066313 online ahead printno abstractpmid35067111 doi101177 13524585211066313,1.0
immunogenicity safety third sarscov2 vaccine dose patients multiple sclerosis weak immune response covid19 vaccination jama neurol 2022 jan 24 doi 101001 jamaneurol20215109 online ahead printno abstractpmid35072702 doi101001 jamaneurol20215109,0.0
worse physical disability associated expression pd1 inflammatory tcells multiple sclerosis patients older appearing brains front neurol 2022 jan 6 12801097 doi 103389 fneur2021801097 ecollection 2021abstractbackground magnetic resonance imaging mri analysis method brainage paradigm offer intuitive prognostic metric brainpredicted age difference brainpad disability multiple sclerosis ms reflecting structural brain health adjusted aging equally cellular senescence reported ms using tcell biomarker cd8+cd57+ objective explored links mriderived brainage bloodderived cellular senescence examined value combining brainpad cd8+cd57+ ilt2+pd1+ tcells predicting disability score ms considered whether agerelated biological mechanisms drive disability methods brainage analysis applied t1weighted mri images disability assessed peripheral blood examined cd8+cd57+ tcell phenotypes linear regression models used adjusted sex age normalized brain volume results included 179 mainly relapsingremitting ms patients high brainpad associated high physical disability mean brainpad +654 512795 cd8+cd57+ ilt2+pd1+ tcell frequency neither associated disability brainpad physical disability predicted interaction brainpad cd8+cd57+ilt2+pd1+ tcell frequency ar 2 0196 yet without improvement compared brainpad alone ar 2 0206 aicc 18 conclusion higher frequency cd8+cd57+ilt2+pd1+ tcells peripheral blood patients older appearing brain associated worse disability scores suggesting role cells development disability ms patients poorer brain healthpmid35069428 pmcpmc8770747 doi103389 fneur2021801097,0.0
remote patient monitoring neuropsychiatric disorders scoping review current trends future perspectives recent publications upcoming clinical trials telemed j e health 2022 jan 24 doi 101089 tmj20210489 online ahead printabstractintroduction telemedicine remote patient monitoring rapidly growing fields scoping review provides update remote patient monitoring neuropsychiatric disorders recent publications upcoming clinical trials methods publications pubmed ichushi published january 2010 february 2021 trials clinicaltrialsgov japanese registries active recruiting march 2021 assessed wearable devices remote management monitoring patients neuropsychiatric disorders searched review focuses disorders 3 publications results identified 44 publications 51 active recruiting trials mostly 2019 2020 research digital devices common parkinsons disease 11 publications 19 trials primarily monitoring motor symptoms preventing falls disorders 35 publications included epilepsy electroencephalogram eeg seizure prediction sleep disorder sleep outcomes behavioral therapies multiple sclerosis physical activity symptoms depression physical activity symptoms behavioral therapies amyotrophic lateral sclerosis symptoms studies focused newly emerging technologies eg inear eeg portable oximeters studies integrated remote symptom monitoring telemedicine discussion currently development digital devices daily symptom monitoring focused parkinsons disease diseases reviewed studies mostly focused physical activity rather psychiatric nonmotor symptoms although validity usefulness many devices established models implementing remote patient monitoring telehealth settings established conclusions verification clinical effectiveness digital devices combined telemedicine needed advance remote patient care neuropsychiatric disorderspmid35073206 doi101089 tmj20210489,0.0
need strategic therapeutic approach multiple sclerosis check ther adv chronic dis 2022 jan 18 1320406223211063032 doi 101177 20406223211063032 ecollection 2022abstractmultiple sclerosis ms common chronic autoimmune neurological disease therapeutic management drastically evolved recent years development specific diseasemodifying therapies dmts together established injectables oral intravenous alternatives now available ms patients significant benefits modulate disease course certain drugs present higher efficacy others profiles frequencies adverse events differentiate well thus due several different treatment alternatives therapeutic approach adopted neurologists requires tactical focus targeted timed meaningful treatment decision integration rational emotional control proper communication skills necessary shared decisionmaking patients perspective paper reinforce necessary concept strategic ms treatment approach using available therapies based scientific evidence current experience apply didactic analogy strategic game chess opening oriented attack ie already early disease stages clinical isolated syndrome correct choice chess pieces move ie among several dmts reassessment reaction different scenarios eg sustained disease activity adverse events family planning advantage realworld data discussed try best approach ultimately successfully approach best personalized ms treatmentpmid35070250 pmcpmc8777338 doi101177 20406223211063032,0.0
wnt signaling pathways role pain processing neuromolecular med 2022 jan 24 doi 101007 s1201702108700z online ahead printabstractthe winglessrelated integration site wnt signaling pathway plays essential role embryonic development nervous system regulation critically involved multiple types neuropathic pain np hivrelated np cancer pain diabetic neuralgia multiple sclerosisrelated np endometriosis pain painful diseases wnt signaling also implicated pain induced sciatic nerve compression injury selective spinal nerve ligation thus wnt signaling pathway may potential therapeutic target nppmid35067780 doi101007 s1201702108700z,0.0
evaluating magnetic resonance diffusion properties together brain volumetry may predict progression multiple sclerosis acad radiol 2022 jan 20s10766332 21 005766 doi 101016 jacra202112015 online ahead printabstractrationale objectives although gold standard predicting future progression clinically isolated syndrome cis clinically definite multiple sclerosis cdms consists mcdonald criteria efforts made employ various advanced mri techniques predicting clinical progression studys main aim evaluate predictive power diffusion tensor imaging dti brain brain volumetry distinguish patients cis future progression cdms without progression following 2 years compare parameters conventional mri evaluationmaterials methods participants underwent mri scan brain dti volumetric data processed various parameters compared study groupsresults found significant differences subgroups patients differing future progression cdms dti volumetric parameters measured fractional anisotropy water diffusion proved strongest predictor clinical conversion among parameters evaluated demonstrating also higher specificity compared evaluation conventional mri images according mcdonald criteriaconclusion conclusion results provide evidence evaluation dti parameters together brain volumetry patients earlystage cis may useful predicting conversion cdms within following 2 years disease coursepmid35067451 doi101016 jacra202112015,0.0
t1#x2f t2weighted ratio surrogate marker demyelination multiple sclerosis commentary mult scler 2022 jan 2213524585211069363 doi 101177 13524585211069363 online ahead printno abstractpmid35067066 doi101177 13524585211069363,1.0
recall response covid19 antigen preserved people multiple sclerosis anticd20 medications pilot study abstractbackgroundantibody responses sarscov2 vaccination impaired people multiple sclerosis ms anticd20 therapies however unclear whether patients received basic immunization prior antib cell medication start respond covid19 booster dose b cells depletedaimto investigate humoral response recall antigen covid19 booster vaccines people ms pwms recently started anticd20 therapy compared people longterm b cell depletionmethodswe enrolled 15 pwms received booster vaccination anticd20 therapy 11 established anticd20 medications therefore vaccinated continuous state b cell depletion cd20vaccine cohort four pwms received basic immunization prior anticd20 therapy commencement booster dose vaccinecd20vaccine cohort conditions b cell depletion assessed sarscov2 specific antibody responses booster vaccination among groups evaluated accompanying b cell numbers proportions peripheral circulationresultsthe booster dose sarscov2 vaccination elicited measurable antibody responses 18 individuals cd20vaccine cohort compared 100 vaccinecd20vaccine cohort antibodylevels significantly higher among patients vaccinecd20vaccine cohort compared cd20vaccine cohort mean 95125 113796 bau ml vs mean 1236 1194 bau ml mean difference 938 bau ml 95 ci 2491629 bau ml p 00001 among vaccinecd20vaccine cohort booster immunization led augmentation spike antibody levels 75 despite concomitant b cell depletion values increased 38 94fold compared basic immunization observed correlation b cell kinetics sarscov2 antibody levelsconclusionour study suggests antibody production recall covid19 antigens preserved pwms despite concomitant anticd20 therapy corroborated bigger cohorts implications management individuals start b cell medications,0.0
markers epsteinbarr virus human herpesvirus6 infection multiple sclerosis clinical progression abstractbackgroundinfections epsteinbarr virus ebv human herpesvirus6 hhv6 implicated multiple sclerosis ms onset little work studied relationships early diseaseobjectiveevaluate associations markers ebv hhv6 infection reactivation ms conversion relapse edss msss among 205 cis participants ebv hhv6 data followed 5 yearsmethodbaseline serological viral load measures ebv hhv6 exposure reactivation measured infectious mononucleosis im history recorded conversion ms relapses assessed annually edss msss measured 5year review determinants ms conversion relapse assessed cox regression disability progression linear regressionresultsim history showed strong positive trend higher relapse risk ahr145 95ci097216 associated ms conversion ahr092 95ci057148 antihhv6 igg titre40 also showed strong positive trends higher relapse ahr161 95ci099263 ms conversion risks ahr148 95ci089246 antihhv6 igg titre640 significantly associated higher msss 015 95ci000 030 also showed strong positive trend higher edss 010 95ci002 021 hhv6 dna detection showed strong positive trends 83 95ci6357 77 95ci4328 higher ms conversion relapse risk antiebvead igg titre associated lower annualised disability progression edss ptrend0037 also showed strong positive trend higher msss ptrend0053 associations seen serological viral load markersconclusionoverall data provides evidence higher hhv6 igg associated increased risk ms conversion relapse borderline significance greater annualised disability progression ebv limited,0.0
research progress dendritic cell vaccines cancer immunotherapy abstractdendritic cell dc vaccines induce specific immune responses can selectively eliminate target cells recent years many studies conducted explore dc vaccination treatment hematological malignancies including acute myeloid leukemia myelodysplastic syndromes well nonleukemia malignancies least two different strategies use dcs promote antitumor immunity situ vaccination canonical vaccination monocytederived dcs modcs leukemiaderived dcs dcleu main types dcs used vaccines aml mds thus far different cancerrelated molecules peptides recombinant proteins apoptotic leukemic cells whole tumor cells lysates dcs dcleu containing vaster antigenic repertoire rna electroporation used antigen sources load dcs enhance dc vaccine efficacy new strategies combination conventional chemotherapy monospecific bispecific antibodies immune checkpointtargeting therapies explored decade trials tribulations much progress made much promise emerged field review summarize recent advances dc vaccine immunotherapy aml mds well nonleukemia malignancies,0.0
ontologybased identification prioritization candidate drugs epilepsy literature background drug repurposing can improve return investment finds new uses existing drugs literaturebased analyses exploit factual knowledge drugs diseases eg databases combine information scholarly publications report use open discovery process scientific literature identify nonexplicit ties disease namely epilepsy known drugs making full use available epilepsyspecific ontologiesresultswe identified characteristics epilepsyspecific ontologies create subsets documents literature subsets generated ranked lists cooccurring neurological drug names varying specificity ranked lists observed high intersection regarding reference lists pharmaceutical compounds recommended treatment epilepsy furthermore performed drug set enrichment analysis ie novel scoring function using adaptive tuning parameter comparing topk ranked lists taking account varying length current position list also provide overview pharmaceutical space context epilepsy including final combined ranked list 70 drug namesconclusionsbiomedical ontologies rich resource can combined text mining identification drug names drug repurposing domain epilepsy ranking drug names related epilepsy provides benefits patients researchers enables quick evaluation statistical evidence hidden scientific literature useful validate approaches drug discovery process,0.0
thermal dysregulation patients multiple sclerosis sarscov2 infection potential therapeutic role exercise abstractthermoregulation homeostatic mechanism disrupted neurological diseases patients multiple sclerosis ms susceptible increases body temperature especially severe neurological signs condition can become intolerable patients suffer febrile infections coronavirus disease2019 covid19 review mechanisms hyperthermia patients ms may encounter infected severe acute respiratory syndrome coronavirus 2 sarscov2 finally thermoregulatory role relevant adaptation regular physical exercise summarized,0.0
gut microbiotaderived metabolite 3idoleacetic acid together lps induces il35+ b cell generation background il35producing bregs treg cells critically regulate chronic illnesses worldwide via mechanisms related disrupting gut microbiota composition however whether gut microbiota regulates il35+ cells remains elusive herein investigated regulatory effects gut microbiota il35+ cells using genetically modified mouse models obesityresultswe first found gut reg4 promoted resistance highfat dietinduced obesity using 16s rrna sequencing combined lcms liquid chromatographymass spectrometry ms demonstrated gut reg4 associated bacteria lactobacillus promoted generation il35+ b cells 3idoleacetic acid iaa presence lps hureg4iectg mice fed highfat diet exhibited marked il35+ cell accumulation adipose tissues also colons whereas decreased il35+ cell accumulation observed adipose colon tissues reg4 knockout ko mice also found reg4 mediated hfdinduced obesity resistance via il35 lower levels iaa also detected peripheral blood individuals obesity compared nonobese subjects mechanistically iaa together lps mediated il35+ b cells pxr tlr4 ko pxr tlr4 impaired generation il35+ b cellsconclusiontogether iaa lps induce generation il35+ b cells pxr tlr4 video abstract,0.0
application mesenchymal stromal cells mscs derivative exosome skin wound healing comprehensive review abstractrecently mesenchymal stromal cells mscs also exosome become gamechanging tool context tissue engineering regenerative medicine mscs due competencies establish skin cells fibroblast keratinocyte also unique attribute suppress inflammation wound site attracted increasing attention among scholars addition mscs capabilities induce angiogenesis result secretion proangiogenic factors accompanied marked antifibrotic activities mainly mediated releases matrix metalloproteinase mmps make rational effective strategy accelerate wound healing small scar since chief healing properties mscs depend paracrine effects appears mscsderived exosomes also can alternative option support wound healing skin regeneration innovative cellfree approach exosomes convey functional cargos eg growth factor cytokine mirna etc mscs target cells thereby affecting recipient skin cells biological events migration proliferation also secretion ecm components eg collagen main superiorities exosome therapy parental mscs diminished risk tumor formation also lower immunogenicity herein deliver overview recent vivo reports rendering therapeutic benefits mscsbased therapies ease skin wound healing improving quality life among patients suffering conditions,0.0
immediate induction varicosities transverse compression uniaxial stretch axon mechanosensation abstractuniaxial stretch believed drive diffuse axonal injury dai mild traumatic brain injury mtbi axonal varicosities enlarged structures along axonal shafts represent hallmark feature dai report axonal varicosities initiate vivo immediately head impact mainly induced transverse compression uniaxial stretch vertical lateral impacts mouse head induced axonal varicosities distinct brain regions changes microglial markers varicosities preferentially formed along axons perpendicular impact direction cultured neurons whereas 50 uniaxial strain needed rapidly induce axonal varicosities nanowrinkled stretch assay physiologicallyrelevant transverse compression effectively induced axonal varicosities fluid puffing assay can generate large nonuniform deformation simulated finite element analysis therefore impact strength direction may determine threshold spatial pattern axonal varicosity initiation respectively partially resulting intrinsic properties axon mechanosensation,0.0
autoantigen microarrays reveal myelin basic protein autoantibodies morphea background morphea autoimmune sclerosing skin disorder despite recent emphasis immune dysregulation morphea role autoantibodies morphea pathogenesis utility biomarkers poorly definedmethodsautoantigen microarray used profile autoantibodies serum participants morphea adults children mac cohort clinical demographic features morphea patients myelin basic protein mbp autoantibodies compared without mbp immunohistochemistry staining subsequently performed morphea skin assess perineural inflammation areas staining immunofluorescence staining mouse brain tissue also performed using patient sera mouse antimyelin basic protein antibody confirm presence mbp antibodies patient seraresultsmyelin basic protein autoantibodies found greater frequency morphea n 50 714 compared systemic sclerosis n 2 67 healthy controls n 7 20 patients mbp antibodies reported pain higher frequencies morphea skin biopsies highlighted immunohistochemistry demonstrated increased perineural inflammation areas mbp expression immunofluorescence staining revealed increased fluorescence signal myelinated areas mouse brain tissue ie axons incubated sera mbp antibodypositive morphea patients compared sera mbp antibodynegative morphea patients epitope mapping revealed target epitopes mbp autoantibodies morphea distinct reported ms included fragments 1130 4160 5170 91110conclusionsa molecular classification morphea based distinct autoantibody biosignatures may used differentially classify morphea identified antimbp potential antibody associated morphea due increased expression morphea compared healthy controls systemic sclerosis patients,1.0
bloodbased biomarkers inflammation amyotrophic lateral sclerosis abstractamyotrophic lateral sclerosis als devastating neurodegenerative disease many processes detected including neuro inflammation many drugs tested als clinical trials failed reach primary endpoints development inclusion different types biomarkers diagnosis clinical trials can assist determining target engagement drug distinguishing als diseases predicting disease progression rate drug responsiveness adverse event ideally among characteristics biomarker als correlates highly disease process central nervous system disease progression conveniently obtained peripheral tissue describe state biomarkers inflammation als focusing peripherally detectable cellular responses blood cells provide new combinatorial directions exploration now feasible due technological advancements,0.0
identification multiple sclerosisrelated genes regulated ebvencoded micrornas b cells abstractbackground multiple sclerosis ms driven interaction genetic susceptibility environmental triggers particularly epsteinbarr virus ebv infection ebvencoded micrornas mirnas abundantly expressed stages ebv infection latency can target viral host cellular mrnas allowing ebvinfected b cells evade host immune response however remains big gap understand roles ebv mirnas target genes ms pathogenesismethods investigated correlation msrelated viruses infection ms risk quantitatively systematic analysis msrelated genes b cells obtained integrating ms susceptibility genes differentially expressed genes b cells comparison differentially expressed genes b cells ebv infection vitro confirmed ebvregulated msrelated genes subsequently obtained target ebv mirnas can regulate genes several online databases constructing pathwaypathway pathwaygene proteinprotein interaction networks screened msrelated genes risk pathways regulated ebv mirnas finally identified target ebv mirnas may directly regulate msrelated genes bioinformatic predictionresults ebv infection showed strongest correlation ms risk total 568 msrelated genes 80 risk pathways b cells obtained identified 112 msrelated genes 18 associated risk pathways ebv involved addition 33 human target genes regulated 33 ebv mirnas overlapped ebvregulated msrelated genes finally 15 target ebv mirnas regulated 7 msrelated genes malt1 bcl10 ifngr2 stat3 cxcr4 ptk2b foxp1 confirmed crucial pathogenic molecules promote initiation development ms nfkappa b malt1 bcl10 pdl1 pd1 ifngr2 stat3 pathways surprisingly ebvmirbhrf125p directly targeting malt1 confirmed experiments foxp1 identified target gene ebvmirbart11conclusions work identified target ebv mirnas regulated msrelated genes well risk pathways may provide novel insight discovering diagnostic biomarkers therapeutic targets ms,0.0
psychological impacts covid19 pandemic individuals living multiple sclerosis rapid systematic review abstractintroduction global spread covid19 raised concerns possible impact mental health people living multiple sclerosis pwms considered potentially vulnerable mental health effects pandemic may subject increased social isolationaim systematically review current evidence impact covid19 pandemic mental health outcomes among pwmsmethod searched four major databases medline embase psychinfo scopus global health covid19 research database included peerreviewed primary research studies using validated healthrelated quality life hrqol psychometric screening tools evaluate mental health outcomes among pwms covid19 pandemic studies reporting data prevalence mental health disorders severity psychological symptoms contributing demographic clinical factors pwms covid19 pandemic includedresults initial search yielded 268 records 19 studies 13 crosssectional 6 longitudinal included conducted peak pandemic host country via online platform main mental health outcomes depression anxiety stress sleep quality hrqol included studies used variety outcome assessment tools study designs prevalence mental health issues depression anxiety stress high among pwms pandemic addition compared control populations pwms experienced severe symptoms depression stress covid19 outbreak however results longitudinal studies demonstrate severity mental health symptoms among pwms pandemic significantly different compared prepandemic periodconclusion although mental health issues anxiety depression common among pwms pandemic current evidence suggests mental health among pwms significantly affected pandemicrelated restrictive measures instead observed differences may result prepandemic differences prevalence severity possible future studies seek address methodological issues identified included studies ensure data collected pandemic can synthesized recommendations policy practice,0.0
podcast b celltargeting therapies multiple sclerosis concerns covid19 neurol ther 2022 jan 23 doi 101007 s40120021003219 online ahead printabstractthe ongoing coronavirus disease 2019 covid19 pandemic continues raise questions people living multiple sclerosis ms healthcare providers common questions included whether people living ms higher risk covid19 severe disease whether certain diseasemodifying therapies dmts ms heighten covid19 risk covid19 vaccinations administered relation ms treatments anticd20 therapies target b cells particular interest given role b cells play response virus causes covid19 sarscov2 vaccines data surfaces pandemic evolves additional questions emerged regarding administration booster shots differences b celltargeting therapies dmts terms immunomodulatory effects podcast article ms specialists discuss challenges ms care covid19 pandemic recent data currently informing clinical decisionmaking pandemic evolves providers continually partner people living ms achieve ms treatment goals informed latest developments covid19 video podcast video mp4 388175 kb pmid35066816 doi101007 s40120021003219,0.0
serum levels lipocalin2 elevated early times african american relapsing remitting multiple sclerosis patients j neuroimmunol 2022 jan 12 364577810 doi 101016 jjneuroim2022577810 online ahead printabstractprevious studies showed depleting liver kinaseb1 lkb1 astrocytes increased inflammatory factors lipocalin2 lcn2 osteopontin opn eae single nucleotide polymorphism snp stk11 encoding lkb1 risk factor ms suggesting increased lcn2 opn contributes risk serum lcn2 opn levels african american female ms patients higher healthy controls levels increased disease duration cases without snp levels decreased duration cases snp increased ms risk associated stk11 snp may due higher lcn2 opn levels early timespmid35066333 doi101016 jjneuroim2022577810,0.0
importance drug titration management patients epilepsy epilepsy behav 2022 jan 20 128108517 doi 101016 jyebeh2021108517 online ahead printabstractthe variable response antiseizure medication asm treatment numerous drug patientrelated factors must considered initiating therapy make drug titration optimal tolerable dose essential component pharmacologic treatment patients epilepsy initiating new asm start low go slow titration approach generally recommended shown reduce risk severe idiosyncratic reactions certain medications improve tolerability regard many frequently occurring central nervous systemrelated adverse effects eg somnolence dizziness many patients epilepsy will require medication changes due lack efficacy intolerability initial regimen occurs patients may switched one monotherapy another receive adjunctive therapy transitioning patient one asm another referred monotherapy conversion transitional polytherapy several strategies tapering baseline asm depending clinical scenario regardless particular strategy goal discontinue baseline asm order prevent increased toxicity due drug load adding asm therapy flexible titration new asm adjustment concomitant asms achieve disease control lowest possible drug load lowest numbers lowest doses may help improve tolerability addon therapy communication patients initiation new therapy may help patients adhere titration schedule allowing reach optimal maintenance dosepmid35066388 doi101016 jyebeh2021108517,0.0
diseasemodifying treatments multiple sclerosis affected incidence neoplasms clinical trials 3 decades metaanalysis metaregression j neurol 2022 jan 23 doi 101007 s00415021109329 online ahead printabstractobjective study aimed estimate incidence neoplasms clinical trials dmts ms test hypothesis dmts increase risk neoplasms duration ms randomized controlled trials rcts methods data extracted 42 rcts dmts published 1991 2020 incidence rate ir neoplasms estimated pooling neoplasms active placebotreatment arm per patientyear neoplasm incidence rate ratio irr active placebotreatment arms used measure effect dmts risk developing neoplasmsresults metaanalysis included 10 638 placebo 16 360 activetreatment arm patients nonsignificant pooled neoplasm incidence rate ratio irr 10797 95 ci 08281 14077 p 05711 heterogeneity i2 0 observed active placebotreatment groups 1991 2020 found significant association incidence neoplasms year publication active placebo arms rcts trials sequestrating depletive dmts associated significantly higher incidence neoplasms active placebotreated arms compared immunomodulatory treatment trialsconclusions study indicates treatment dmts modified risk neoplasms ms clinical trials 1991 2020 may reflect low carcinogenic potential dmts neoplasia latencies far exceed typical ms trial observation periodspmid35066607 doi101007 s00415021109329,0.0
glutathione targeted tragacanthic acidchitosan nonviral vector brain delivery mirna219a5p vitro#x2f vivo study int j biol macromol 2022 jan 20s01418130 22 001155 doi 101016 jijbiomac202201100 online ahead printabstractmultiple sclerosis ms progressive chronic demyelinating neurodegenerative disease symptoms diminished stimulated remyelination although administration microrna219a5p mir219 seems recover damages hampered challenging delivery genes central nervous system across bloodbrain barrier enhance cns delivery mir219 novel nonviral targeted vector appraised conjugating chitosan ch tragacanthic acid ta glutathione glu nanoparticles characterized injected cuprizone model ms mice investigate vivo features resulting polyplex transmission electron microscopy luxol fast blue staining proteolipid protein 1 plp1 overexpression confirmed compact myelin sheaths following administration targeted mir219 nanoparticles positron emission tomography pet scan also demonstrated reduced inflammation higher cell regeneration brain fluorescence microscopy vivo imaging employed identify mir219 accumulation patterns mice polyplex led mir219 overexpression crystallin alpha b upregulation apolipoprotein e downregulation concluded glutathione targeted ch ta nanoparticles exploited feasible nonviral vector mir219 specific targeting brain mir219 overexpression inflammation abatement mspmid35066026 doi101016 jijbiomac202201100,1.0
inflammasome signaling aging brain agerelated neurodegenerative diseases mol neurobiol 2022 jan 23 doi 101007 s12035021026835 online ahead printabstractinflammasomes intracellular protein complexes members innate immune system activation regulation play essential role maintaining homeostatic conditions exogenous endogenous stimuli inflammasomes occur cytosolic proteins assemble complex recognition pathogenassociated dangerassociated molecular patterns patternrecognition receptors host cells formation inflammasome complex elicits signaling molecules proinflammatory cytokines interleukin1 interleukin 18 via activation caspase1 canonical inflammasome pathway whereas caspase11 case mouse caspase4 caspase5 case humans noncanonical inflammasome pathway resulting pyroptotic inflammatory cell death ultimately leads neuroinflammation neurodegenerative diseases inflammasome activation particularly microglial cells macrophages linked aging well agerelated neurodegenerative diseases accumulation abnormal misfolded proteins acts ligand inflammasome activation neurodegenerative diseases although recent studies revealed inflammasomes functionality vitro vivo models many inflammasome signaling cascade activations biological aging neuroinflammation neurodegeneration still ambiguous review comprehensively unveil cellular molecular mechanisms inflammasome activation neuronal aging agerelated neurodegenerative disorders alzheimers disease parkinsons disease huntingtons disease multiple sclerosis prion disease amyotrophic lateral sclerosispmid35066762 doi101007 s12035021026835,0.0
estrogen enhanced expression il17 tissueresident memory t cells uterus via interferon regulatory factor 4 abstracttissueresident memory t cells mucosal epithelial sites play important role pathogen clearance immunosurveillance participating physiological processes different barrier sites immune cells uterus face protection infections tolerate allogeneic fetus successful pregnancy previous study found tissueresident memory t cells enriched human murine uterus highly expressed il17 promoted invasion trophocytes vitro current study found t cells uterus blood spleens expressed higher levels estrogen receptors injection estrogen mice increased proportion t cells uterus spleens vivo via cxcr3cxcl10 chemokine axis addition found estrogen enhanced production il17 ifn vivo vitro via interferon regulatory factor 4 rort pstat3 mrna protein levels analysis cell transcriptome sequence identified multiple differentially expressed genes estrogen control t cells study demonstrated estrogen directly act t cells uterus enhance production il17 might promote invasion trophocytes furthermore study might provide new idea estrogen increased prevalence autoimmune diseases women enhancing t cellderived il17 production uterus uncover critical pathological roles estrogen development autoimmune diseases,0.0
prospective observational multicenter study assessing adherence interferon beta1b therapy patient satisfaction using betaconnect autoinjector neurol ther 2022 jan 22 doi 101007 s40120022003231 online ahead printabstractintroduction important achieve good persistence adherence diseasemodifying therapies dmts achieve best outcomes chronic diseases multiple sclerosis ms betaconnect device electronic autoinjector dmt interferon beta1b betaseron designed improve patients injection experience monitor adherence observational study aimed assess patient adherence persistence interferon beta1b therapy well patientreported satisfaction us populationmethods prospective observational multicenter study conducted 146 adult patients relapsingremitting ms clinically isolated syndrome newly prescribed currently established interferon beta1b therapy nave betaconnect device followed 6month observation periodresults among 91 patients completed study overall mean adherence rate 825 659 patients adherent least 80 duration 6month period 6 months 989 patients less 60day gap therapy 115 patients provided satisfaction data 905 patients either satisfied satisfied betaconnect deviceconclusion study shows betaconnect device associated high adherence interferon beta1b therapy patients ms patients also reported high degrees satisfaction device therefore may viable delivery option help adherence persistence potentially leading improved clinical outcomespmid35064907 doi101007 s40120022003231,0.0
hervw envelope triggers abnormal dopaminergic neuron process drd2#x2f pp2a#x2f akt1#x2f gsk3 schizophrenia risk viruses 2022 jan 14 14 1 145 doi 103390 v14010145abstractan increasing number studies begun considering human endogenous retroviruses hervs potential pathogenic phenomena previous research suggests hervw envelope hervw env hervw family envelope protein elevated schizophrenia patients contributes pathophysiology schizophrenia dopamine da hypothesis cornerstone research clinical practice related schizophrenia found concentration da expression da receptor d2 drd2 significantly higher schizophrenia patients healthy individuals intriguingly positive correlation hervw env da concentration depth analyses showed marked consistency hervw env drd2 schizophrenia studies vitro indicated hervw env increase da concentration regulating da metabolism induce expression drd2 coip assays laser confocal scanning microscopy indicated cellular colocalization direct interaction drd2 hervw env additionally hervw env caused structural functional abnormalities da neurons studies showed hervw env trigger pp2a akt1 gsk3 pathway via drd2 wholecell patchclamp analysis suggested hervw env enhanced sodium influx drd2 conclusion uncovered relationship hervw env dopaminergic system da neurons considering gnbac1 selective monoclonal antibody msrvspecific epitope promised therapy treating type 1 diabetes multiple sclerosis ms clinical trials understanding precise function hervw env dopaminergic system may provide new insights treatment schizophreniapmid35062349 doi103390 v14010145,0.0
principal component analysis approach estimate disability status patients multiple sclerosis using japanese claims data neurol ther 2022 jan 22 doi 101007 s40120022003240 online ahead printabstractintroduction claims databases preferred research multiple sclerosis ms condition characterized low prevalence long disease course however japanese claims databases contain information disease severity disability status ms aimed explore possibility utilizing principal component analysis pca estimate ms severity using japanese claims databasemethods ms severity score developed using pca factors related functional systems expanded disability status scale edss higher disease severity 74 diagnoses 68 drug prescriptions 77 procedures extracted claims database april 2008august 2018 score pc1 score developed patientyeareach year first diagnosis excluding year first diagnosis based first principal component included factors finally patientyears classified quartiles based pc1 score demographic information medical status analyzedresults database contained 7067 patients ms highest score group higher mean age 554 02 mean standard error years lower percentage women 644 07 longer mean disease duration first diagnosis 81 01 years lowest score group 433 02 years 684 08 60 01 years respectively addition pc1 score patient positively correlated disease duration diagnosisconclusion developed pc1 score indicate ms severity using information japanese claims database since changes demographic features observed consistent findings previous research score might represent ms severity extent research necessary validate score clinical measurement disability edsspmid35064908 doi101007 s40120022003240,0.0
mental health multiple sclerosis covid19 outbreak delicate balance fear contagion resilience j clin psychol med settings 2022 jan 22 doi 101007 s1088002209849w online ahead printabstractthe current study aimed exploring relationship objective disability illness perceptions resilience fear covid19 psychological distress ie anxiety depression stress people multiple sclerosis pwms second wave covid19 outbreak group 122 pwms recruited italian university hospital took part crosssectional monocentric study hierarchical multiple linear regression analyses performed assess strength hypothesized associations results indicated differently cognitive impairment motor disability positively associated anxiety however accounting subjective illness perception association longer significant moreover accounting protective risk factors models even illness perception longer significant highlighting central role resilience fear covid19 explaining negative emotional outcomes implications clinical interventions psychoeducational trainings discussedpmid35064863 doi101007 s1088002209849w,0.0
development technologies monitoring sixminute walk test systematic review sensors basel 2022 jan 12 22 2 581 doi 103390 s22020581abstractin pandemic time monitoring progression diseases affected rehabilitation complicated remote monitoring may help solve problem using mobile devices embed lowcost sensors can help measure different physical parameters many tests can applied remotely one sixminute walk test 6mwt 6mwt submaximal exercise test assesses aerobic capacity endurance allowing early detection emerging medical conditions changes paper presents systematic review use sensors measure different physical parameters performance 6mwt focusing various diseases sensors implemented methodologies performed prisma methodology search conducted different databases including ieee xplore acm digital library sciencedirect pubmed central filtering papers related 6mwt sensors selected 31 papers analyzed detail analysis discovered measurements 6mwt primarily performed inertial magnetic sensors likewise research studies related test focus multiple sclerosis pulmonary diseasespmid35062542 doi103390 s22020581,0.0
bloodbrain barrier dysregulated covid19 serves cns entry route sarscov2 stem cell reports 2022 jan 3s22136711 21 006500 doi 101016 jstemcr202112011 online ahead printabstractneurological complications common covid19 although sarscov2 detected patients brain tissues entry routes resulting consequences well understood show pronounced upregulation interferon signaling pathways neurovascular unit fatal covid19 investigating susceptibility human induced pluripotent stem cell hipsc derived brain capillary endotheliallike cells bcecs sarscov2 infection found bcecs infected recapitulated transcriptional changes detected vivo bcecs compromised paracellular tightness found sarscov2 basolateral compartment transwell assays apical infection suggesting active replication transcellular transport virus across bloodbrain barrier bbb vitro moreover entry sarscov2 bcecs reduced antispike antiangiotensinconverting enzyme 2 ace2 antineuropilin1 nrp1 specific antibodies transmembrane protease serine subtype 2 tmprss2 inhibitor nafamostat together data provide strong support sarscov2 brain entry across bbb resulting increased interferon signalingpmid35063125 doi101016 jstemcr202112011,0.0
advances ongoing research treatment autoimmune neuromuscular junction disorders lancet neurol 2022 feb 21 2 189202 doi 101016 s14744422 21 004634abstractmyasthenia gravis lamberteaton myasthenic syndrome antibodymediated autoimmune diseases neuromuscular junction usually present weakness ocular muscles proximal muscles limb trunk prognosis regarding muscle strength functional abilities quality life survival generally good however patients respond treatment symptomatic drugs corticosteroids steroidsparing immunosuppressive drugs remain cornerstone treatment past years new biological agents complement fcrn receptor bcell antigens tested clinical trials new therapies extend possibilities targeted immunotherapies promise exciting new options relatively rapid mode action challenges use might occur barriers due increase cost care additional considerations choice drugs potential consequences infection vaccination due covid19 pandemicpmid35065041 doi101016 s14744422 21 004634,0.0
physical activity sedentary behavior timing fatigued nonfatigued adults multiple sclerosis arch phys med rehabil 2022 jan 18s00039993 22 000181 doi 101016 japmr202112022 online ahead printabstractobjective present study examined devicemeasured physical activity levels sedentary behavior participation different times day ie morning midday evening adults multiple sclerosis ms differed fatigue statusdesign crosssectional surveysetting remote survey study managed universitybased research laboratoryparticipants populationbased sample 1 000 participants ms sent recruitment materials north american research committee multiple sclerosismain outcome measures participants n218 completed fatigue severity scale fss measure fatigue severity divided subgroups fatigued fss score 4 nonfatigued fss score 4 participants wore actigraph gt3x+ nondominant hip seven days measuring physical activity ie light physical activity lpa moderatetovigorous physical activity mvpa steps sedentary behaviorresults fatigued participants engaged less mvpa f 1 216 185 p0001 fewer steps f 1 216 278 p0001 sedentary time f 1 216 82 p0005 nonfatigued participants regardless group highest levels lpa f 17 3557 729 p0001 mvpa f 18 3953 230 p0001 occurred morning middle day lowest levels evening regardless group highest levels sedentary behavior occurred evening similar levels morning evening f 16 3545 843 p0001 regardless group participants steps middle day followed morning evening f 18 3839 847 p0001 conclusions results suggest physical activity timing considered future development delivery behavior interventions focus increasing physical activity reducing sedentary behavior among adults ms fatiguepmid35063422 doi101016 japmr202112022,0.0
safety efficacy rituximab relapse prevention myelin oligodendrocyte glycoprotein immunoglobulin g mogigg associated disorders mogad systematic review metaanalysis j neuroimmunol 2022 jan 13 364577812 doi 101016 jjneuroim2022577812 online ahead printabstractintroduction myelin oligodendrocyte glycoprotein immunoglobulin g mogigg associated disorders mogad neuroimmunological disorder manifesting episodes adem optic neuritis transverse myelitis brainstem encephalitis cns manifestations notably distinct multiple sclerosis ms neuromyelitis optica spectrum disorders nmosd current treatment strategy highdose intravenous methylprednisolone followed maintenance immunotherapy relapse prevention purpose study systematically create compelling evidence addressing role rituximab relapse prevention among patient mogadmethods study follows prisma preferred reporting items systematic reviews metaanalyses guideline searched pubmed embase google scholar english language papers published 2010 2021 individual study proportions metaanalyzed yield pooled relapsefree patient proportion individual studies mean pre posttreatment annualized relapse ratio arr expanded disability status scale edss used calculate overall mean differenceresults metaanalysis includes 13 studies 238 subjects rituximab treatment 55 95 ci 049061 mogad patients remained relapsefree study found rituximab therapy arr lowered 136 95 ci 102171 p 0001 similarly detected 052 95 ci 008 096 p 002 difference edss score starting rituximab medication handful included studies documented adverse events safety profile rituximab treatment mogad effectively determinedconclusion metaanalysis shows rituximab effectively prevents relapses mogad patientspmid35063726 doi101016 jjneuroim2022577812,1.0
covid19 vaccination willingness acceptability multiple sclerosis patients cross sectional study iran vaccines basel 2022 jan 17 10 1 135 doi 103390 vaccines10010135abstractmultiple sclerosis ms chronic predominantly immunemediated degenerative disease central nervous system due prolonged use immunomodulatory immunosuppressive medications vaccine hesitancy common among ms patients main aim current study evaluate willingness acceptability covid19 vaccination patients ms multicenter crosssectional questionnairebased clinical study 892 patients completed questionnaire may june 2021 questionnaire consisted demographic data ms diseaserelated factors history covid19 infection vaccination existing comorbidities statistical analysis performed using spss software version 19 overall 68 participants expressed willingness vaccinated major causes vaccine refusal patients fear reducing efficacy disease modifying drugs dmds upon vaccination well distrusting vaccines overestimation bias power innate immunity potential covid19 resistance demographic factors affected vaccination enthusiasm study findings show significant correlation age comorbidity vaccine willingness onethird patients received vaccine information healthcare providers majority received data official broadcasting channels social media however despite several concerns willingness covd19 vaccination iranian ms patients remarkablepmid35062796 doi103390 vaccines10010135,0.0
multiple sclerosis personality personality characteristics newly diagnosed multiple sclerosis association mood cognition j neurol sci 2022 jan 11 434120145 doi 101016 jjns2022120145 online ahead printabstractbackground neuropsychiatric changes common multiple sclerosis ms personality persons ms pwms understudied despite implications health behaviours symptoms quality life qol objective assess baseline personality characteristics relationship information processing speed ips mood persons early msmethods retrospective chart review 384 pwms psychometric testing within 2 years diagnosis february 2012 may 2021 testing included neofive factor inventory symbol digit modalities test hospital anxiety depression scale hads results participants highly agreeable 537 impaired ips 605 anxiety depression present 194 505 87 226 participants respectively females agreeable conscientious neuroticism conscientiousness extraversion moderatehigh correlations anxiety depression despite weak correlations conscientiousness extraversion openness pwms impaired versus normal ips significant personality differencesconclusions individuals recently diagnosed ms agreeable typically impaired ips often anxiety depression significant personality differences exist sexes pwms without anxiety depression early identification neuropsychiatric traits pwms may improve treatment adherence symptoms qolpmid35063812 doi101016 jjns2022120145,0.0
activation annexin a2 signaling bloodbrain barrier mouse model multiple sclerosis j neurochem 2022 jan 22 doi 101111 jnc15578 online ahead printabstractbloodbrain barrier bbb dysfunction fundamental cause multiple sclerosis identifying molecules responsible urgent matter protein expression comprehensively quantified bbb experimental autoimmune encephalomyelitis eae mice model multiple sclerosis using swath method concerning tight junction molecules level expression claudin5 previous immunohistochemical analysis confirmed downregulated eae remained unchanged expression claudin11 occludin decreased 069 062fold respectively brain capillaries isolated eae mice number cellcell junctional molecules including esam cadm1 cadm2 cadm3 cadm4 hepacam also downregulated levels expression icam1 vcam1 directly mediate infiltration lymphocytes across bbb increased eae mice 33 26fold respectively expression cxadr possibly facilitates adhesion migrating cells also increased 35fold interestingly various members annexin anxa family also upregulated brain capillaries isolated eae mice pathway associated cell infiltration tight junction disruption series molecules involved anxa2 signaling anxa2 ptp1b ahnak s100a11 cd44 kindlin2 integrin 5 fibronectin fibrinogen upregulated anxa2 selectively abundantly expressed endothelial cells brain daily administration anxa2 inhibitor lcklsl peptide significantly suppressed development eae mice summary activation anxa2 signaling bbb appear play important role pathogenesis eaepmid35064931 doi101111 jnc15578,0.0
cordycepin prevents ameliorates experimental autoimmune encephalomyelitis inhibiting leukocyte infiltration reducing neuroinflammation biochem pharmacol 2022 jan 18114918 doi 101016 jbcp2022114918 online ahead printabstractmultiple sclerosis ms neuroinflammatory autoimmune disease characterized multifocal perivascular infiltration immune cells central nervous system cns cordycepin 3deoxyadenosine adenosine analogue initially extracted fungus cordyceps militarisa one candidates multiple actions investigated crdycepin attenuated activation lpsinduced mouse bone marrowderived dendritic cells bmdcs human monocytederived dendritic cells modcs inhibition akt erk nfb ros pathways impaired migration bmdcs downregulation adhesion molecules chemokine receptors vitro experimental autoimmune encephalomyelitis eae model preventive treatment cordycepin decreased expression trafficking factors cns inhibited secretion inflammatory cytokines ifn il6 tnf il17 attenuated disease symptoms chemokine array indicated cordycepin treatment reversed high levels ccl6 parres2 il16 cxcl10 ccl12 brain spinal cord eae mice consistent rnaseq data moreover cordycepin suppressed release neuroinflammatory cytokines activated microglial cells macrophages th17 cells tc1 cells th1 cells vitro furthermore cordycepin treatment exerted therapeutic effects attenuating disease severity early disease onset stage late disease progression stage study suggests cordycepin treatment may prevent occurrence ms inhibiting dc activation migration also potentially ameliorates progression ms reducing neuroinflammation may provide insights development new approaches treatment mspmid35063441 doi101016 jbcp2022114918,0.0
impact lifetime coffee tea loads multiple sclerosis severity clin nutr espen 2022 feb 47199205 doi 101016 jclnesp202112014 epub 2021 dec 23abstractbackground aims association lifestyle factors multiple sclerosis ms disease severity progression investigated lesser extent compared susceptibility disease aimed assess impact lifetime coffee tea consumption ms severitymethods design crosssectional study two hundred eight patients 139 females 69 males consecutively recruited department neurology novara italy asked lifetime consumption coffee tea lifetime intensity consumption cups day estimated weighted sum mean number standard cups drunk per day different ages measure cumulative lifetime load exposure expressed terms cupyears disease severity estimated multiple sclerosis severity score msss hladrb115 hlaa02 genotyping performed 167 patientsresults msss associated status coffee tea consumer amount cups day cupyears odds ratios falling upper tertile msss distribution 130 95 confidence interval ci 047358 coffee consumers 13 cups day 114 95ci 033395 48 cups day vs nonconsumers 069 95ci 035134 tea consumers vs nonconsumers however heavy consumers coffee 48 cups day frequently progressive form small consumers 13 cups day nonconsumers 19 vs 14 vs 0 significantly higher age ms onset 366 103 315 95 286 81 years p 0001 although reaching statistical significance coffee consumers positive hlaa02 sixfold risk worst tertile compared never consumers whereas risk 13 coffee consumers negative alleleconclusions coffee tea intake associated different severity ms however exclude possible effect higher doses coffee subgroup progressive patientspmid35063202 doi101016 jclnesp202112014,0.0
therapeutic promise carotenoids antioxidants antiinflammatory agents neurodegenerative disorders biomed pharmacother 2022 feb 146112610 doi 101016 jbiopha2021112610 epub 2022 jan 4abstractneurodegenerative disorders nds including alzheimers disease parkinsons disease amyotrophic lateral sclerosis huntingtons disease multiple sclerosis various diseasespecific causal factors pathological features common characteristic nds oxidative stress os takes place due elevated generation reactive oxygen species progression nds furthermore pathological condition nds including increased level protein aggregates can lead chronic inflammation microglial activation carotenoids cts naturally occurring pigments play significant role averting brain disorders 750 cts present nature widely available plants microorganisms animals cts accountable red yellow orange pigments several animals plants colors usually indicate various types cts cts exert various bioactive properties characteristic structure including antiinflammatory antioxidant properties due protective properties cts levels cts human body markedly linked prevention treatment multiple diseases including nds review summarized relationship os neuroinflammation nds addition also particularly focused antioxidants antiinflammatory properties cts management ndspmid35062074 doi101016 jbiopha2021112610,0.0
hemostasis components therapeutic targets autoimmune demyelination clin pharmacol ther 2022 jan 21 doi 101002 cpt2532 online ahead printabstractseveral studies multiple sclerosis ms experimental autoimmune encephalitis eae shed light vascular mechanisms contributing ms pathogenesis dysregulation hemostatic pathways revealed play pivotal role review numerous findings providing evidence involvement hemostasis components ms pathogenesis highlight might considered potential therapeutic targets disease literature search articles january 1950 september 2021 conducted pubmed scopus consistent body evidence supports proinflammatory activity activated platelets ms pathogenesis beneficial effect aspirin administration eae clinical course neuropathological findings ms subjects experimental studies eae revealed dysregulation coagulation fibrinolysis system autoimmune demyelination fibrin deposition central nervous system interaction cd11b receptor microglia cells seems drive neuroinflammation autoimmune demyelination however present controversial clinical data available implementation drugs targeting fibrin deposition ms therapy conclusion targeting platelet activation receptors fibrin ogen deserve research hopefully purpose new drugs pharmacologic paraphernalia ms neurologistspmid35064575 doi101002 cpt2532,1.0
osteochondral regeneration femoral medial condyle using scaffoldfree 3d construct synovial membranederived mesenchymal stem cells horses background medical interventions subchondral bone cysts horses extensively studied study investigated regeneration articular cartilage subchondral bone scaffoldfree threedimensional 3d constructs equine synovial membranederived mesenchymal stem cells smmscs isolated three ponies expanded 10 107 cells passage 2 p2 resultssmmscs strongly positive cd11a cd18 cd44 major histocompatibility complex mhc class moderately positive cd90 cd105 mhc class ii negative cd34 cd45 flow cytometry differentiated osteogenic chondrogenic adipogenic lineages trilineage differentiation assay culturing smmscs p3 prepared construct diameter 63 mm height 50 mm comprising approximately 1920 spheroids containing 30 104 cells construct confirmed positive type collagen negative type ii collagen alcian blue safranino upon histological analysis subsequently implanted osteochondral defect diameter 68 mm depth 50 mm right femoral medial condyle contralateral left femoral defect served control 3 6 months surgery radiolucent volume rv mm3 defects calculated based multiplanar reconstruction computed tomography ct images magnetic resonance mr images evaluated using modified twodimensional mr observation cartilage repair tissue mocart grading system macroscopic gross microscopic histological characteristics scored according international cartilage repair society icrs scale compared control sites implanted defects showed lower rv percentages better total mocart scores higher average gross scores higher average histological scoresconclusionsimplantation scaffoldfree 3dconstruct smmscs osteochondral defect regenerate original structure cartilage subchondral bone 6 months postsurgery horses indicating potential technique treating equine subchondral bone cysts,0.0
contribution relapseassociated worsening overall disability accrual patients relapsingonset multiple sclerosis mediation analysis abstractobjective neurological disability accumulation patients relapsingonset multiple sclerosis ms commonly attributed relapseassociated worsening raw progression independent relapse activity pira using mediation model research aimed investigate quantify contributions raw pira overall disability accrualmethods clinical data containing expanded disability status scale edss scores duration attack number demographics collected 121 patients relapsingonset ms china included mediation model two phases defined early phase clinical onset edss 3 later phase greater edss 3results clinical attack number partly mediated relationship duration neurological disability durationattackedss score early phase ratio indirect raw total effect 0414 mediator effect became negligible 10 later phase predominating direct effect pira onset age positively correlated edss scores early stage independent clinical attack number direct effect significant indirect effect association insignificant later besides compared females male patients appeared relapse less frequently reaching edss 3 vulnerable accelerated progression thatconclusions relapsingonset ms pira major contributor irreversible disability accrual throughout whole disease course albeit raw also partly involved early stage correlations disabled outcome onset age sex vary different phases,0.0
efficacy safety oral immunotherapy children aged 13 years peanut allergy immune tolerance network impact trial randomised placebocontrolled study summarybackgroundfor young children peanut allergy dietary avoidance current standard care aimed assess whether peanut oral immunotherapy can induce desensitisation increased allergic reaction threshold therapy remission state nonresponsiveness discontinuation immunotherapy populationmethodswe randomised doubleblind placebocontrolled study five us academic medical centres eligible participants children aged 12 younger 48 months reactive 500 mg less peanut protein doubleblind placebocontrolled food challenge dbpcfc participants randomly assigned use computer 21 allocation ratio receive peanut oral immunotherapy placebo 134 weeks 2000 mg peanut protein per day followed 26 weeks avoidance participants study staff investigators masked group treatment assignment primary outcome desensitisation end treatment week 134 remission avoidance week 160 key secondary outcome assessed dbpcfc 5000 mg intentiontotreat population safety immunological parameters assessed population trial registered clinicaltrialsgov nct03345160findingsbetween aug 13 2013 oct 1 2015 146 children median age 393 months iqr 308447 randomly assigned receive peanut oral immunotherapy 96 participants placebo 50 participants week 134 68 71 95 ci 6180 96 participants received peanut oral immunotherapy compared one 2 00511 50 received placebo met primary outcome desensitisation risk difference rd 69 95 ci 5979 p00001 median cumulative tolerated dose week 134 dbpcfc 5005 mg iqr 37555005 peanut oral immunotherapy versus 5 mg 0105 placebo p00001 avoidance 20 21 95 ci 1330 96 participants receiving peanut oral immunotherapy compared one 2 00511 50 receiving placebo met remission criteria rd 19 95 ci 1028 p00021 median cumulative tolerated dose week 160 dbpcfc 755 mg iqr 02755 peanut oral immunotherapy 0 mg 055 placebo p00001 significant proportion participants receiving peanut oral immunotherapy passed 5000 mg dbpcfc week 134 longer tolerate 5000 mg week 160 p0001 participant receiving placebo desensitised week 134 also achieved remission week 160 compared placebo peanut oral immunotherapy decreased peanutspecific ara h2specific ige skin prick test basophil activation increased peanutspecific ara h2specific igg4 weeks 134 160 use multivariable regression analysis participants receiving peanut oral immunotherapy younger age lower baseline peanutspecific ige predictive remission participants 98 peanut oral immunotherapy vs 80 placebo least one oral immunotherapy dosing reaction predominantly mild moderate occurring frequently participants receiving peanut oral immunotherapy 35 oral immunotherapy dosing events moderate symptoms treated epinephrine 21 participants receiving peanut oral immunotherapyinterpretationin children peanut allergy initiation peanut oral immunotherapy age 4 years associated increase desensitisation remission development remission correlated immunological biomarkers outcomes suggest window opportunity young age intervention induce remission peanut allergyfundingnational institute allergy infectious disease immune tolerance network,0.0
increased admission serum total bile acids can associated decreased 3month mortality patients acute ischemic stroke background bile acids bas play important role lipid metabolism atherosclerosis also antiapoptotic neuroprotective effects however studies focused relationship total bile acid tba levels severity prognosis acute ischemic stroke ais objectivesthe aim study investigate potential associations fasting serum tba levels admission stroke severity inhospital complication incidence 3 month allcause mortality patients aismethodsa total 777 consecutive ais patients enrolled study divided four groups according quartiles serum tba levels admission univariate multivariate logistic regression analyses used explore relationship fasting tba levels stroke severity inhospital complications 3month mortality ais patientsresultspatients group q3 lowest risk severe ais nihss 10 regardless adjustments confounders p 005 hospitalization 115 patients 148 stroke progression nihss score increased 2 222 patients 286 developed least one complication significant difference among four groups p 005 significant difference incidence pneumonia urinary tract infection uti hemorrhagic transformation ht gastrointestinal bleeding gib seizures renal insufficiency ri among four groups p 005 total 114 patients 147 died various causes including inhospital deaths 3month followup including 42 213 26 133 19 99 27 139 patients groups q1 q2 q3 q4 respectively significant differences p 0013 adjusting confounding factors risk death decreased p trend 005 groups q2 q3 q4 compared group q1 values 036 016080 030 013070 029 013065 respectivelyconclusionstba levels inversely associated 3month mortality ais patients significantly associated severity stroke incidence complications,1.0
humoral cellular immune responses sars cov2 vaccination persons multiple sclerosis nmosd patients receiving immunomodulatory treatments abstractbackgroundvaccination sars cov2 results excellent personal protection severe course covid19 people multiple sclerosis pwms vaccination efficacy may reduced immunomodulatory medicationsobjectiveto assess vaccination induced cellular humoral immune response pwms receiving disease modifying therapiesmethodsin monocentric observational study pwms patients neuromyelitis optica quantified cellular humoral immune responses sars cov2resultspwms receiving glatiramer acetate interferon dimethylfumarate cladribine natalizumab intact humoral cellular immune responses following vaccination sars cov2 bcell depleting therapies reduced bcell responses affect t cell responses sphingosin1phospate s1p inhibitors strongly reduced humoral cellular immune responsesthere good agreement interferon gamma release assay tspot assay used measure viral antigen induced tcell responsesconclusionthis study demonstrates s1p inhibitors impair cellular humoral immune response sars cov2 vaccination whereas patients receiving bcell depleting therapies mount intact cellular immune response data can support clinicians counselling pwms nmosd patients covid 19 pandemic,0.0
cardiac valve calcification associated mortality hemodialysis patients retrospective cohort study background cardiac valve calcification cvc common endstage renal disease esrd investigated effect cvc allcause cardiovascular cv mortality maintenance hemodialysis mhd patientsmethodsa retrospective cohort study conducted 434 hemodialysis patients underwent echocardiography qualitative assessment valve calcification complete followup data january 1 2014 april 30 2021 baseline data cvc noncvc groups compared kaplanmeier method used analyse allcause cardiovascular mortality association cvc allcause cardiovascular mortality evaluated using multivariate cox regression analysisresultsoverall 272 patients mitral valve calcification mvc 318 aortic valve calcification avc echocardiography patients cvc showed significantly higher allcause logrank p 0001 cardiovascular logrank p 0001 mortality rates patients without cvc multivariate regression analyses mvc hr 1517 p 0010 avc hr 1433 p 0028 significant factors associated allcause mortality mvc hr 2340 p 0001 avc hr 2410 p 0001 also significant factors associated cardiovascular mortalityconclusionsmvc avc increased risk allcause cardiovascular mortality mhd patients regular followup echocardiography useful method risk stratification mhd patients,0.0
pregnancy outcomes following maternal paternal exposure teriflunomide danish ms population abstractbackground teriflunomide tfl oral drug used treatment multiple sclerosis ms due possible teratogenicity contraindicated women childbearing potential additionally low risk malemediated embryofetal toxicity described drug can transmitted via semen study investigated association adverse perinatal outcomes newborns either maternal paternal exposure tflmethods danish multiple sclerosis registry used identify patients treated teriflunomide 1st september 2013 31st december 2018 data merged nationwide national registries identify pregnancies potential exposure tfl exposure defined conception occurring least 30 consecutive days treatment either treatment within two years treatment discontinuation exposed pregnancies matched 14 controls general population individual outcomes adverse perinatal events namely preterm birth congenital malformations small gestational age sga stillbirth low apgar score used form composite outcome adverse event used analysis logistic regression used estimate association adverse event newborns either maternal paternal exposure tflresults total 112 tflexposed pregnancies included 49 maternal exposure 63 paternal exposure among women 21 49 pregnancies terminated 18 electively three spontaneously remaining 28 pregnancies resulted healthy newborns 3 preterm none newborns presented malformations sga low apgar score among men 63 pregnancies resulted birth 4 63 63 preterm major malformations registered 3 event newborn presented low apgar score sga increased association adverse event found newborns tfl exposure relative controls 103 95 ci 050213 conclusion find increased prevalence spontaneous abortion preterm birth congenital malformations low apgar score sga newborns maternal paternal exposure tfl compared general population however sample small draw firm conclusions,0.0
escalation vs early intense therapy multiple sclerosis j pers med 2022 jan 17 12 1 119 doi 103390 jpm12010119abstractthe treatment strategy multiple sclerosis ms highly controversial debate currently 19 drugs approved however clear evidence guide fundamental decisions treatment chosen first place treatment failure suboptimal response considered treatment considered cases escalation strategy consists starting treatment drugs low sideeffect profile low efficacy escalating drugs higher efficacywith potential sideeffectsif necessary strategy prevailed years however evidence supporting strategy based shortterm studies hope benefits will stand long term studies usually consider heterogeneity disease limited effect relapses longterm hand early intense therapy strategy refers starting treatment drugs higher efficacy beginning despite less favorable sideeffect profile approach takes advantage socalled window opportunity hope maximize clinical benefits longterm present debate remains open review will critically review strategies provide summary current evidence strategy without aiming reach definite conclusionpmid35055434 doi103390 jpm12010119,0.0
serum vitamin d biomarker autoimmune psychiatric neurodegenerative diseases diagnostics basel 2022 jan 6 12 1 130 doi 103390 diagnostics12010130abstractvitamin d steroid hormone regulating calciumphosphorus homeostasis immune response brain function past thirty years increasing number cohort studies metaanalyses randomized controlled trials rtcs evaluated serum levels 25hydroxyvitamin d 25 oh d considered vitamin d status biomarker patients affected neurological psychiatric autoimmune diseases although association low 25 oh d serum levels prevalence diseases found still unclear whether serum 25 oh d measurement can clinically useful biomarker diagnosis prognosis predicting treatment response neurodegeneration mental illness immunemediated disorders lack standardized data well discrepancies among studies analytical methods cutoffs endpoints study sets weakened findings achieved hindered pooling data consequently hampered drawing conclusions narrative review summarizes main findings studies performed serum 25 oh d neurological psychiatric autoimmune diseases clarifies whether serum 25 oh d can used reliable biomarker diseasespmid35054296 doi103390 diagnostics12010130,0.0
application quot risk ambulatory disabilityquot road score quot realworldquot singlecenter multiple sclerosis cohort cns neurosci ther 2022 jan 21 doi 101111 cns13806 online ahead printabstractsurvival analysis reaching edss 40 based road score 4 dashed line 4 solid line cox regression analysis unadjusted regression analysis b regression controlled sex immunotherapy groups trajectory treatment changes followuppmid35060326 doi101111 cns13806,0.0
synthesis biological investigation bile acidpaclitaxel hybrids molecules 2022 jan 12 27 2 471 doi 103390 molecules27020471abstractchenodeoxycholic acid ursodeoxycholic acid cdca udca respectively conjugated paclitaxel ptx anticancer drugs highyield condensation reaction bile acidptx hybrids baptx investigated proapoptotic activity towards selection cancer cell lines well healthy fibroblast cells chenodeoxycholicptx hybrid cdcptx displayed cytotoxicity cytoselectivity similar ptx whereas ursodeoxycholicptx hybrid udcptx displayed anticancer activity towards hct116 colon carcinoma cells pacific blue pb conjugated derivatives cdcptx udcptx cdcptxpb udcptxpb respectively also prepared via multistep synthesis evaluating ability enter tumor cells cdcptxpb udcptxpb flow cytometry clearly showed cdca udca conjugation ptx improved incoming hct116 cells allowing derivatives enter cells 999 respect 35 case ptx mean fluorescence intensity analysis cell populations treated cdcptxpb udcptxpb also suggested cdcptxpb greater ability pass plasmatic membrane udcptxpb hybrids showed significant lower toxicity respect ptx nih3t3 cell linepmid35056786 doi103390 molecules27020471,0.0
clinical predictors neurogenic lower urinary tract dysfunction persons multiple sclerosis diagnostics basel 2022 jan 13 12 1 191 doi 103390 diagnostics12010191abstractbackground multiple sclerosis patients often develop neurogenic lower urinary tract dysfunction potential risk upper urinary tract damage diagnostic tools urodynamics bladder diary uroflowmetry postvoid residual recommendations use controversialobjective aimed identify clinical parameters indicative neurogenic lower urinary tract dysfunction multiple sclerosis patientsmethods 207 patients prospectively assessed independent presence lower urinary tract symptoms analyzed expanded disability status scale scores uroflowmetry postvoid residual rate urinary tract infections standardized voiding frequency voided volume correlation urodynamic findingsresults found significant correlation postvoid residual odds ratio 417 confidence interval ci 1202246 urinary tract infection rate 391 ci 113210 voided volume 453 ci 1851199 increased standardized voiding frequency 740 ci 2153966 urodynamic findings indicative neurogenic lower urinary tract dysfunction expanded disability status scale shows correlation parameters except postvoid residual also associated reduced bladder compliance potential risk kidney damageconclusion therefore bladder diary urinary tract infection rate routinely assessed identify patients require urodynamicspmid35054358 doi103390 diagnostics12010191,0.0
vitro methodologies study role advanced glycation end products ages neurodegeneration nutrients 2022 jan 15 14 2 363 doi 103390 nu14020363abstractadvanced glycation end products ages can present food endogenously produced biological systems formation associated chronic neurodegenerative diseases alzheimers disease parkinsons disease multiple sclerosis amyotrophic lateral sclerosis implication ages neurodegeneration related ability bind agespecific receptors ability precursors induce socalled dicarbonyl stress resulting crosslinking protein damage however mode action underlying role neurodegeneration remains unclear research carried observational clinical studies vitro studies may help elucidate underlying modes action review presents discusses vitro methodologies used research potential role ages neuroinflammation neurodegeneration overview reveals main concepts linking ages neurodegeneration current findings available advisable vitro models study role moreover major questions regarding role ages neurodegenerative diseases challenges discrepancies research field discussedpmid35057544 doi103390 nu14020363,0.0
role efferocytosis neurodegenerative diseases neurol sci 2022 jan 21 doi 101007 s10072021058356 online ahead printabstractefferocytosis critical role maintaining tissues organs homeostasis removing apoptotic cells essential human health disturbances efferocytosis may result indifferent illnesses case inadequate clearance dead cells content cells released fact induces damages tissue leads prolonged inflammation unsuitable phagocytosis apoptotic cells involved occurrence well expansion numerous human chronic inflammatory diseases studies shown age dependence neurodegenerative diseases largely due neuroinflammation loss neurons thus cause brains functional disorders efferocytosis coupled antiinflammatory responses contribute elimination dying neurons neurodegenerative diseases disruption may make risk factor numerous human chronic inflammatory diseases multiple sclerosis alzheimers disease glioblastoma rett syndrome study review efferocytosis molecular pathways role neurodegenerative diseases order discover new treatment option cure patientspmid35059903 doi101007 s10072021058356,0.0
assessing visually guided reaching people multiple sclerosis without selfreported upper limb impairment plos one 2022 jan 21 17 1 e0262480 doi 101371 journalpone0262480 ecollection 2022abstractthe ability accurately complete goaldirected actions reaching glass water requires coordination sensory cognitive motor systems systems impaired like people multiple sclerosis pwms deficits movement arise date characterization upper limb performance pwms typically limited results attained selfreported questionnaires clinical tools aim characterize visually guided reaching performance pwms thirtysix participants 12 pwms reported upper limb impairment msr 12 pwms reported experiencing upper limb impairment msnr 12 age sexmatched control participants without ms ctl reached 8 targets virtual environment seeing visual representation hand form cursor screen reaches completed dominant nondominant hands participants able complete visually guided reaching task hand landed target however pwms showed noticeably atypical reaching profiles compared control participants accordance observations analyses reaching performance revealed msr group variable respect time took initiate complete movements compared ctl group performance msnr group differ significantly either ctl msr groups individuals msnr group less consistent performance compared ctl group together findings suggest pwms without selfreported upper limb impairment deficits planning control movements argue deficits observed movement pwms report upper limb impairment may arise due participants compensating impaired movement planning processespmid35061785 doi101371 journalpone0262480,0.0
relationship cognitive dysfunction postural stability multiple sclerosis medicina kaunas 2021 dec 21 58 1 6 doi 103390 medicina58010006abstractbackground objectives multiple sclerosis ms demyelinating disease central nervous system cns commonly characterized balance dysfunction fatigue syndrome cognitive impairment goal study determine association cognitive functions static posture control materials methods research group consisted 76 randomized ms patients icdg 350 hospitalized neurological rehabilitation clinic medical university lodz group divided three subgroups according cognitive assessment based mini mental state examination mmse patients 65 years age montreal cognitive assessment moca age 65 fatigue syndrome assessed using fatigue severity scale fss postural stability using stabilometric platform results men demonstrated poorer stabilometric platform measurements women statistically significant differences observed patients without dysfunction severe cognitive impairment results stabilometric platform found correlate body mass index three groups patients spearmans test conclusions body mass index cognition impact postural stability ms patients moderate disability fatigue syndromepmid35056313 doi103390 medicina58010006,1.0
recommendations diagnosis treatment multiple sclerosis relapses j pers med 2021 dec 22 12 1 6 doi 103390 jpm12010006abstractminimizing risk relapse essential multiple sclerosis ms none treatments currently available capable completely preventing relapses treatment episodes remains cornerstone ms care objective manuscript reduce uncertainty improve quality care neurological process article addresses definitions key concepts recommendations clinical examination classification criteria magnetic resonance imaging biomarkers specific therapeutic counsels including special populations pregnant breastfeeding women children algorithm treating ms relapses also providedpmid35055321 doi103390 jpm12010006,0.0
comparison magnetic resonance imaging methods assess multiple sclerosis lesions implications patient characterization clinical trial design diagnostics basel 2021 dec 30 12 1 77 doi 103390 diagnostics12010077abstractmagnetic resonance imaging mri sensitive imaging modality identifying inflammatory demyelinating lesions critical clinical diagnosis ms evaluating drug responses many unique means probing brain tissue status including conventional t1 t2 weighted imaging t1wi t2wi t2 fluid attenuated inversion recovery flair magnetization transfer myelin water fraction diffusion tensor imaging dti phasesensitive inversion recovery susceptibility weighted imaging swi study combined modalities single wellcontrolled investigation goals study compare different mri measures lesion visualization quantification evaluate repeatability various imaging methods healthy controls compare quantitative susceptibility mapping qsm myelin water fraction measure shortterm longitudinal changes white matter ms patients map tissue properties white matter hyperintensities using stage strategically acquired gradient echo imaging additionally outcomes study anticipated aid choice efficient imaging protocol reducing redundancy information alleviating patient burden sequences used t2 flair t2wi showed lesions differentiate putative demyelinating lesions inflammatory lesions fusion swi t2 flair used study suggests practical efficient imaging protocol combining t2 flair t1wi stage swi qsm can used rapidly image ms patients find lesions study demyelinating inflammatory characteristics lesionspmid35054244 doi103390 diagnostics12010077,1.0
advance care planning neurodegenerative disorders scoping review int j environ res public health 2022 jan 12 19 2 803 doi 103390 ijerph19020803abstractadvance care planning acp increasingly acknowledged key step enable patients define goals preferences future medical care together carers health professionals aimed map evidence acp neurodegenerative disorders conducted scoping review searching pubmed inceptiondecember 28 2020 addition trial review dissertation registers 9367 records included 53 studies mostly conducted europe 45 uscanada 41 within last five years twentysix percent studies qualitative followed observational 21 reviews 19 randomized controlled trials rcts 19 quasiexperimental 11 mixedmethods 4 twothirds studies addressed dementia followed amyotrophic lateral sclerosis 13 brain tumors 9 rct interventions dementia consisted educational programs facilitated discussions videos patients carers conclusion research needed investigate barriers facilitators acp uptake well develop test interventions almost neurodegenerative disorders common set outcome measures targeting discrete acp behavior validated across different diseases cultures also neededpmid35055625 doi103390 ijerph19020803,0.0
design oral sustainedrelease pellets modeling simulation approach improve compliance repurposing sobrerol pharmaceutics 2022 jan 11 14 1 167 doi 103390 pharmaceutics14010167abstractsobrerol oral mucolytic agent recent study showed promise treating multiple sclerosis human equivalent dose 486 mg sobrerol administered thrice daily ie 1459 mg daily dose demonstrated highest therapeutic efficacy repurposing use also points poor compliance administration study oral sustainedrelease pellets sobrerol successfully developed evaluated manufacturing conditions drug release kinetics design target drug product used modeling simulation approach establish predictive model oral pharmacokinetic profile exploring characteristics correlations corresponding pharmacokinetics pharmacodynamics sobrerol absorption lag time 018 h timescaling vitroin vivo correlation tinvitro 0494 tinvivo 00904 gastrointestinal transit time 8 h minimum effective concentration 161 g ml duration action 128 h results showed frequency administration daily dose remarkably reduced 333 ie thrice twice daily 228 respectively indicates prototype approach can adopted rapidly developing modifiedrelease dosage form sobrerol improvement compliance administration therapeutic efficacypmid35057064 doi103390 pharmaceutics14010167,0.0
local autoimmune encephalomyelitis model rat brain precise control lesion placement plos one 2022 jan 21 17 1 e0262677 doi 101371 journalpone0262677 ecollection 2022abstractdevelopment novel animal model multiple sclerosis ms reproducible predictable lesion placement enhance discovery effective treatments therefore like combine advantages demyelination model experimental autoimmune encephalomyelitis eae provide local autoimmune encephalomyelitis lae inside rat brain induced demyelinating lesion immunizing male wistar rats followed bloodbrain barrier opening protein vascular endothelial growth factor stereotactic injection confirmed immunization myelin epitopes minor neurological impairment histological assessment confirmed lesion development 3 7 days postinjection approach sufficient develop demyelinating lesion high reproducibility low morbiditypmid35061807 doi101371 journalpone0262677,1.0
information processing speed assessed letter digit substitution test croatian sample multiple sclerosis patients diagnostics basel 2022 jan 4 12 1 111 doi 103390 diagnostics12010111abstractcognitive impairment common complaint people multiple sclerosis pwms study objective determine psychometric properties letter digit substitution test ldst measures information processing speed investigate impact relevant predictors ldst achievement pwms design crosssectional study included 87 pwms 154 control subjects validity ldst examined hierarchical regression model used explore relevant predictors ldst success ldst excellent construct validity expressed differences pwms control subjects convergent validity ldst supported significant moderate correlation expanded disability status scale edss 036 p 005 significantly strong correlation multiple sclerosis impact scale msis29 physical subscale r 064 p 001 ldts score well differentiated pwms considering age education edss disease duration comorbidity medication therapy using ldst criterion variable pwms results showed consistent evidence age education edss impact ldst performance best cutoff score 35 discriminated control ms group ldst proved valid test assessing information processing speed pwmspmid35054278 doi103390 diagnostics12010111,0.0
successful treatment dimethyl fumarate child relapsingremitting multiple sclerosis brain dev 2022 jan 17s03877604 21 002473 doi 101016 jbraindev202112010 online ahead printabstractintroduction early disease control diseasemodifying drugs important improving prognosis multiple sclerosis ms children dimethyl fumarate dmf oral diseasemodifying drug ms adults relatively stable disease however use young children heavily documented current literature report case pediatric patient relapsingremitting ms treated dmfcase report 3yearold boy history common cold symptoms developed unsteadiness somnolence magnetic resonance imaging revealed multiple white matter lesions symptoms recurrent dmf prescribed 6 years age due relapse episode oculomotor disability facial paralysis however disease progression continued new lesions noted age 7 thus dose dmf increased 240 mg day relapse observed three years sequelae severe side effects absentconclusions dmf may useful oral diseasemodifying drug preventing recurrence young children mspmid35058083 doi101016 jbraindev202112010,0.0
therapeutic benefits shortarm human centrifugation multiple sclerosisa new approach front neurol 2022 jan 4 12746832 doi 103389 fneur2021746832 ecollection 2021abstractshortarm human centrifugation sahc proposed robust countermeasure treat deconditioning prevent progressive disability case secondary progressive multiple sclerosis based longterm physiological knowledge derived space medicine missions artificial gravity training seems promising physical rehabilitation approach toward prevention musculoskeletal decrement due confinement inactivity present study proposes novel infrastructure based sahc investigate hypothesis artificial gravity ameliorates degree disability patient submitted 4week training programme including three weekly sessions 30 min intermittent centrifugation 152 g sessions cardiovascular muscle oxygen saturation smo2 electroencephalographic eeg responses monitored whereas neurological physical performance tests carried intervention cardiovascular parameters improved way reminiscent adaptations aerobic exercise smo2 decreased sessions concomitant increased g load training progressed smo2 suffering limb dropped effects suggesting increased oxygen use similar seen hard exercise eeg showed increased slow decreased fast brain waves brain reorganization plasticity evidenced functional connectivity alterations multiplesclerosisrelated disability balance capacity also improved overall study provides novel evidence supporting sahc promising therapeutic strategy multiple sclerosis based mechanical loading thereby setting basis future randomized controlled trialspmid35058870 pmcpmc8764123 doi103389 fneur2021746832,0.0
cancellous bonelike tissue replacement calcinosis patients systemic sclerosis multiple external root resorption bone rep 2022 jan 8 16101165 doi 101016 jbonr2021101165 ecollection 2022 junabstractcalcinosis frequently observed patients systemic sclerosis ssc fundamental treatment calcinosis yet established followup calcinosis subcutaneous surface often spontaneously extracted remains confined fibrous tissues previously identified new symptom ssc patients multiple external root resorption merr patients calcifications nasal spine report first time calcinosis nasal spine patients merr can replaced cancellous bonelike tissue patients 1 2 62yearold japanese female 45yearold japanese female respectively merr previously treated ssc patient 1 limited type positive anticentromere antibody patient 2 diffuse type positive antiscl70 antissa antibodies patient 3 57yearold female merr previously treated ssc diffuse type positive antiscl70 antibody underwent denosumab injection osteoporosis conebeam computed tomography cbct ct images calcifications nasal spine patient 1 2 replaced cancellous bonelike tissue patient 3 serum laboratory examination performed assess systemic bone disease three patients normal clinical data within references apart slightly higher 1 25dihydroxyvitamin d levels patient 1 ssc patients calcinosis maxillofacial area need examined carefully bone replacement using cbct ctpmid35059476 pmcpmc8760497 doi101016 jbonr2021101165,0.0
complementary alternative therapies multiple sclerosis systematic literature classification analysis acta neurol belg 2022 jan 21 doi 101007 s13760021018473 online ahead printabstractintroduction aim multiple sclerosis ms disease determined inflammatory demyelination neurodegeneration central nervous system cns despite extensive utilization complementary alternative medicine cam ms need comprehensive evidence regarding application management ms symptoms manuscript systematic literature review classification slr cam therapies management ms symptoms based international classification functioning disability health icf modelmethod studies published 1990 2020 pubmed science direct scopus proquest google scholar using cam therapies management ms symptoms analyzedresults thirtyone papers subject analyzed classified findings review clearly show mindfulness yoga reflexology frequently used managing ms symptoms moreover papers used mindfulness yoga cam therapy management ms symptoms mostly devoted mental functions fatigue depression cognition neuromuscular functions gait muscle strength spasticity sensory function balance addition reflexology vastly used management mental functions ms patientsconclusion evidence suggested cam therapies patients ms potential target enhancement numerous elements outlined icf model although use cam therapies ms symptom management promising need strict clinical trials future research direction concentrate methodologically powerful studies find potential efficacy cam interventionpmid35060096 doi101007 s13760021018473,1.0
employment health visits mental health mortality parents chronically ill child danish nationwide populationbased cohort study eur j pediatr 2022 jan 21 doi 101007 s00431021043342 online ahead printabstractchronic diseases children can impact parents may overlooked clinical setting aim investigate associations chronic diseases children parents employment health care utilization mental health mortality matched cohort study using nationwide populationbased data denmark included parents children 18 years acute disseminated encephalomyelitis multiple sclerosis type 1 diabetes inflammatory bowel disease rheumatoid arthritis juvenile idiopathic arthritis 20082015 reference group parents unaffected children outcomes parental employment early retirement cash benefits income health care utilization eg general practitioner hospital visits mental health visits psychiatry psychology clinics antidepressant drug redemptions mortality included 13 769 parents chronically ill child 138 606 control parents annual income unaffected twoparent families childs disease onset twoparent families increased hazard early retirement 25 95 ci 101154 p 004 parents chronically ill child increased rate antidepressant drug redemptions psychology psychiatry visits hazard ratio 137 95 ci 128146 1year followup b increased health care utilization increased marginal mean primary care 1 95 ci 100102 p 0005 hospitalaffiliated visits 19 95 ci 114124 p 00001 hospital admissions 14 95 ci 109120 p 00001 c 69 increased mortality hazard 95 ci 130218 p 00001 parents younger 50 years comorbidities albeit small absolute numbersconclusion pediatric chronic diseases negatively associated parental employment mental health mortality increased health care utilization known studies impact pediatric chronic diseases parental health qualitative knowledge unavailable regarding impact parental work health care utilization mortality new among 13 769 parents chronically ill child 138 606 control parents parents chronically ill child 37 increased antidepressant drug redemptions parents 50 years without comorbidities 69 increased mortality hazard medical doctors consider parental health condition societal challenges related child chronic diseasepmid35059826 doi101007 s00431021043342,0.0
dual role beta 2 adrenoreceptor modulation il17 ifngamma production t cells multiple sclerosis int j mol sci 2022 jan 8 23 2 668 doi 103390 ijms23020668abstractnorepinephrine neurotransmitter also immunomodulatory effect involved multiple sclerosis ms pathogenesis study aimed clarify role 2adrenoreceptor norepinephrinemediated modulation interleukin17 il17 interferon ifn production play critical pathogenetic role ms cd4+ t cells obtained twentyfive relapsingremitting ms patients sixteen healthy subjects cultured ex vivo norepinephrine 2adrenoreceptor antagonist agonist followed cytokine production analysis using elisa norepinephrine suppressed il17 ifn production anticd3 anticd28microbeadstimulated cd4+ t cells groups blockade 2adrenoreceptor specific antagonist ici 118551 enhanced norepinephrinemediated il17 suppression decreased inhibitory effect ifn production ms patients contrast 2adrenoreceptor agonist formoterol influence norepinephrines inhibitory effect cytokine production groups blockade 2adrenoreceptor even absence exogenous norepinephrine suppressed il17 production influence ifn production groups conversely 2adrenoreceptor activation formoterol decreased ifn production affect il17 production groups data illustrate inhibitory effect norepinephrine il17 ifn production cd4+ t cells ms inhibitory effect norepinephrine ifn production cd4+ t cells ms mediated via 2adrenoreceptor activationpmid35054851 doi103390 ijms23020668,0.0
18ffdgpet correlates aging disease course als revealed distinct pvc approaches eur j radiol open 2022 jan 13 9100394 doi 101016 jejro2022100394 ecollection 2022abstractpurpose partial volume effect pve complicates pet studies neurodegenerative diseases since decreased 18ffdg retention might influenced atrophyrelated changes cortical regions multiple partial volume correction pvc methods therefore developed application amyotrophic lateral sclerosis als still rare additionally even metabolic changes established als study yet investigated may influenced aging disease course aim present study therefore apply compare multiple pvc approaches explore aging disease courserelated hypometabolism alsmethods pet mri data 15 als patients analyzed using petsurfer implement 4 distinct pvc methods nopvc meltzer mz mllergrtner mg symmetric geometric transfer matrix sgtm method region interest roi 18ffdg value regressed subject age disease durationresults mg sgtm application almost halved number regions showing significant agerelated hypometabolism effect observed disease course distribution identified regions varied three distinct patterns emerged regions showing significant age disease courserelated effect across different methods regions yielding significance mg sgtm application regions maintaining significance nopvc mz applicationconclusions significant changes distribution aging disease courserelated hypometabolism observed effect underlying structural status considered supporting need investigate impact pve petassessed metabolic changes clinical research settingspmid35059473 pmcpmc8760536 doi101016 jejro2022100394,0.0
thrombotic thrombocytopenic purpura interferon beta1atreated patient diagnosed relapsingremitting multiple sclerosis case report life basel 2022 jan 7 12 1 80 doi 103390 life12010080abstractbackground secondary thrombotic thrombocytopenic purpura ttp due interferon beta1a intramuscular im treatment uncommon adverse effect cases multiple sclerosis patients reported worldwide ttp together haemolytic uremic syndrome hus classic forms thrombotic microangiopathy characterized smallvessel platelet microthrombi manifest clinically similar manner common signs symptoms include bruises ecchymosis neurologic symptoms renal impairment interferon beta1a represents one firstline therapies relapsingremitting multiple sclerosis due accessibility efficacycase presentation 36yearold woman previously diagnosed relapsingremitting multiple sclerosis received weekly intramuscular injections betainterferon1a avonex 30 mcg 9 months treatment presented bruises ecchymosis limbs torso epistaxis gingival bleeding aggravated within 48 h persistent headache nonresponsive common analgesics haematology tests revealed typical results thrombotic microangiopathy including severe thrombocytopenia 4000 mm3 microangiopathic haemolytic anaemia frequent schistocytes peripheral blood smear betainterferon administration ceased upon initiation methylprednisolone symptoms remittedconclusions case study portrayed particular association remission phase multiple sclerosis violent onset interferoninduced thrombotic thrombocytopenic purpurapmid35054473 doi103390 life12010080,0.0
effects quarantine applied covid19 pandemic mental health quality life patients multiple sclerosis healthy controls neurol sci 2022 jan 21 doi 101007 s10072022059017 online ahead printabstractbackground coronavirus outbreak emerged wuhan china late 2019 spread world changed livesobjective investigate effects quarantine depression anxiety sleep quality fatigue sf36 multiple sclerosis ms patients covid19 outbreak differences healthy controls hc methods eightysix ms patients 65 hc patients included study participants filled various scales facetoface interviews mental health assessment january 15 february 15 2021results groups compared terms beckd inventory p 0001 becka inventory p 0010 fs p 0001 patient group significantly higher results physical functioning p 0001 physical role limitation p 0001 energy vitality rates p 0010 general health perception p 0001 higher hc group ms patients divided according edss scores becka p 0001 beckd p 0001 psqi p 0006 scores patients edss 3 higher emotional role restriction rates p 0006 energy vitality p 0018 pain p 0005 significantly lower edss 3 ms patients divided two groups covid19 compared sf36 subscale scores pain p 0049 mental status p 0030 obtained significant differences two groupsconclusions study revealed ms patients susceptible new normal emerged pandemic period among priority groups supported terms mental health well physical healthpmid35061136 doi101007 s10072022059017,0.0
effect dynamic neuromuscular stabilization balance trunk function people multiple sclerosis protocol randomized control trial background multiple sclerosis chronic disabling neurological disease among young people one major complaints patients multiple sclerosis pwms falling number factors risk factors falling including balance disorder spasticity core stability cs exercises trunk muscle strengthening exercises can improve balance mobility reduce falling dynamic neuromuscular stabilization dns exercise new functional rehabilitation strategy optimizes motor function based principles developmental kinesiology trial will evaluate effectiveness dns comparison cs balance spasticity falling pwmsmethodsa total 64 pwms 30 50 years old expanded disability status scale edss 2 5 will recruited neurophysiotherapy clinic faculty rehabilitation sciences iran university medical sciences participate 2armed parallel study participants will randomly divided two groups receive cs exercise dns exercise participants will receive exercise treatment 15 sessions period 5 weeks 3 sessions per week primary outcome measures will balance falling rate fear falling patient mobility well spasticity will measured secondary outcomes outcome measures will measured baseline day completion 15th session 17 weeksdiscussiondynamic neurostabilization exercises utilize subconscious stimulation special zones reflexively mediate diaphragm core stabilization muscles extremely effective individuals reduced somatosensory movement awareness findings proposed study expected benefit knowledge base physiotherapist can good alternative rehabilitation program even reduce medication use patients multiple sclerosis exercises easy understand applicable patients partners welltrial registrationthe trial registered iran registry organization code irct20140222016680n5 approved april 7th 2020 address irct administration team central library building iran university campus hemmat freeway next milad tower tehran iran postal code1449614535,0.0
factors affecting spinefemur discordance percentage young adult mean dualenergy xray absorptiometry elderly population retrospective study background several retrospective studies reported spinefemur discordance bone mineral density bmd values however average age individuals studies mid50s younger typical age individuals requiring treatment primary osteoporosis therefore aimed investigate factors associated discordance percentage young adult mean yam lumbar spine femoral neck elderly populationmethodswe evaluated 4549 dualenergy xray absorptiometry dxa measurements obtained 2161 patients 269 men 1892 women january 2014 december 2017 hospital individuals one eligible set measurements first record used investigated patients age sex body mass index current smoking status alcohol consumption use steroids presence diabetes mellitus presence rheumatoid arthritisresultsthe mean age patients 764 89 years older age p 0001 male sex p 0001 diabetes mellitus p 0007 significantly associated spinefemur discordance percentage yamconclusionthe frequency magnitude spinefemur discordance percentage yam dxa scans increased age notably 774 patients 90s spinefemur discordance 10 yam furthermore frequency spinefemur discordance higher men patients diabetes mellitus suggesting percentage yam lumbar spine may reliable diagnosis osteoporosis patients factors,0.0
immunometabolic rewiring tumorigenesis antitumor immunotherapy abstractcellular metabolism constitutes fundamental process biology tumor initiation progression cellular component cancerous niche undergoes dramatic metabolic reprogramming adapting challenging microenvironment hypoxia nutrient deprivation stresses metabolic hallmarks cancer extensively studied metabolic states immune cells less well elucidated review metabolic disturbance fitness immune system tumor microenvironment tme focusing impact oncometabolites function immune cells clinical significance targeting metabolism antitumor immunotherapy metabolic alterations immune system tme offer novel therapeutic insight cancer treatment,0.0
extended bcell depletion beyond 6months patients receiving ocrelizumab rituximab cns demyelinating disease abstractobjectives measure duration bcell depletion cohort patients receiving ocrelizumab rituximab multiple sclerosis ms neuromyelitis optica spectrum disorders nmosd methods retrospectively searched database patients diagnosed ms nmosd receiving ocrelizumab rituximab available cd19 measurements collected demographic data infusion doses infusion dates cd19 absolute counts percentages collection dates paired infusion subsequent cd19 measurements recorded next infusion discarding measurements done washout period 30 days infusion applied three definitions bcell depletion stringent absolute bcell count 20 cells ulresults 695 patients demyelinating diseases database period january 1st 2010 march 1st 2020 identified 188 patients 178 ms 10 nmosd received ocrelizumab rituximab available cd19 measurements 1054 cd19 measurements captured bcell depletion defined recorded far 228 months ocrelizumab infusion 223 months rituximab infusion 90 bcell measurements done 8 months 210 days ocrelizumab infusion 45 50 measurements showed bcell depletion similarly rituximab 113 measurements 49 43 showed bcell depletionconclusions study demonstrates bcell depletion ocrelizumab rituximab continues beyond traditional 6month reinfusion interval many patients report provides data can support clinical trials testing increasing interval reinfusion ocrelizumab rituximab beyond 6months guided bcell measurements,1.0
metrantes preserves bloodbrain barrier inhibiting ccr1#x2f src#x2f rac1 pathway intracerebral hemorrhage mice background cc chemokine receptor type 1 ccr1 endogenous ligand ccl5 participate pathogenesis neuroinflammatory diseases however much remains unknown regarding ccl5 ccr1 signaling bloodbrain barrier bbb permeability intracerebral hemorrhage ich methodsa total 250 cd1 male mice used ich induced via autologous whole blood injection either metrantes selective ccr1 antagonist metrantes combined rac1 crispr activator administered mice 1 h ich postich assessments included neurobehavioral tests brain water content bbb integrity hematoma volume western blot immunofluorescence staining ccr1 ligand rccl5 src crispr knockout nave mice used elucidate detrimental ccl5 ccr1 src signalingresultsbrain endogenous ccr1 ccl5 upregulated ich mice peak 24 h ccr1 expressed endothelial cells astrocytes neurons metr treatment reduced brain edema neurobehavioral impairment well preserved bbb integrity tight junction protein expression ich mice metr treatment decreased expression psrc rac1 albumin mmp9 increased claudin5 occludin zo1 tight junction proteins ich effects regressed using rac1 crispr activator administration rccl5 nave mice increased expression psrc rac1 albumin mmp9 decreased levels claudin5 occludin zo1 tight junction proteins effects nave mice reversed src crispr ko conclusionsour findings demonstrate ccr5 inhibition metr improves neurological deficits ich preserving bbb integrity inhibiting ccr1 src rac1 signaling pathway mice thus metr therapeutic potential management ich patients,0.0
heart rate heart rate variability patients chronic inflammatory joint disease role pain duration insular cortex background chronic inflammatory joint diseases cijd linked increased cardiovascular morbidity mortality decisive reason dysregulation autonomic nervous system responsible control cardiovascular function far cause changes autonomic nervous system functions remains elusive study investigate role chronic pain insular cortex autonomic control cardiac functioning patients cijdmethodswe studied autonomic nervous system assessment heart rate heart rate variability hrv rest cognitive stimulation furthermore investigated insular cortex volume performing surfacebased brain morphometry freesurfer study 47 participants recruited 22 individual age sexmatched pairs magnetic resonance imaging analyses 14 hrv analyses available patients data used analysisresultspain duration negatively correlated resting heart rate patients chronic inflammatory joint diseases n 20 multiple linear regression model including cijd patients heart rate rest dependent variable found significant positive relationship heart rate rest volume left insular cortex significant negative relationship heart rate rest volume right insular cortex however found significant differences hrv parameters insular cortex volumes groupsconclusionsin study provide evidence suggest insular cortex involvement process ans changes due chronic pain cijd patientsthe study preregistered german clinical trials register https wwwdrksde drks00012791 date registration 28 july 2017,0.0
trends administrative prevalence multiple sclerosis utilization patterns disease modifying drugs germany abstractbackground study aimed describe recent developments multiple sclerosis ms prevalence germany assess utilization patterns diseasemodifying drugs dmds methods used nationwide outpatient claims data statutory health insurance shi years 2012 2019 covering 87 total german population annual crosssectional analyses ms prevalence measured percentage shi population affected ms annual agentspecific prescription prevalence dmds calculated number patients receiving dmd per 1000 ms patientsresults 2012 2019 prevalence ms increased gradually 027 034 overall dmd prescription prevalence ms patients rose 436 per 1 000 ms patients 2012 483 2019 2012 2019 prescription prevalence interferonbeta 1a interferonbeta 1b decreased sharply 1802 708 61 802 341 57 respectively contrast prescription prevalence teriflunomide 2012 85 2019 545 fingolimod 2012 285 2019 638 exhibited pronounced increase factors 54 22 respectivelyconclusion ms prevalence germany steadily increased recent years ms treatment patterns changed markedly indicating shifting predominance dmd injectable drugs oral medications,0.0
transdiagnostic vivo magnetic resonance imaging markers neuroinflammation biol psychiatry cogn neurosci neuroimaging 2022 jan 17s24519022 22 000192 doi 101016 jbpsc202201003 online ahead printabstractaccumulating evidence suggests inflammation limited archetypal inflammatory diseases multiple sclerosis instead represent intrinsic feature many psychiatric neurological disorders typically classified neuroinflammatory importantly growing body research suggests neuroinflammation can observed early prodromal stages disorders certain circumstances may lead tissue damage traditional methods assess neuroinflammation include serum cerebrospinal fluid markers positron emission tomography pet methods require invasive procedures radiation exposure lack exquisite spatial resolution magnetic resonance imaging mri therefore increasing interest noninvasive neuroimaging tools evaluate neuroinflammation reliably high specificity mri provide information cellular level facilitates characterization several biophysical tissue properties closely linked neuroinflammatory processes purpose review evaluate potential mri noninvasive accessible costeffective technology image neuroinflammation across neurological psychiatric disorders provide overview current developing mri methods used study different aspects neuroinflammation weigh strengths shortcomings novel mri contrast agents increasingly able target inflammatory processes directly therefore offering high degree specificity particularly used conjunction multitissue biophysical diffusion mri compartment models capability methods characterize several aspects neuroinflammatory milieu will likely push mri forefront neuroimaging modalities used characterise neuroinflammation transdiagnosticallypmid35051668 doi101016 jbpsc202201003,0.0
risk getting covid19 people multiple sclerosis casecontrol study neurol neuroimmunol neuroinflamm 2022 jan 19 9 2 e1141 doi 101212 nxi0000000000001141 print 2022 marabstractbackground objectives several studies assessed risk factors associated severity covid19 outcomes people multiple sclerosis pwms potential role diseasemodifying therapies dmts demographic clinical factors risk acquiring sarscov2 infection evaluated far objective study assess risk factors contracting sarscov2 infection pwms using data collected italian ms register imsr methods casecontrol 12 study set cases included pwms confirmed diagnosis covid19 controls included pwms without confirmed diagnosis covid19 groups propensity scorematched date covid19 diagnosis date last visit region residence healthy controls included study covid19 risk estimated multivariable logistic regression models including demographic clinical covariates impact dmts assessed 3 independent logistic regression models including one following covariates last administered dmt previous dmt sequences place last treatment administeredresults total 779 pwms confirmed covid19 cases matched 1 558 pwms without covid19 controls 3 models comorbidities female sex younger age significantly associated p 002 higher risk contracting covid19 patients receiving natalizumab last dmt 95 ci 238 166342 p 00001 underwent escalation treatment strategy 157 116213 p 0003 significantly higher covid19 risk moreover pwms receiving last dmt requiring hospital access 165 134204 p 00001 showed significant higher risk taking selfadministered dmts homediscussion casecontrol study embedded imsr showed pwms higher covid19 risk younger frequently female individuals comorbidities longlasting escalation approach last therapies expose patients hospital environment seem significantly increase risk sarscov2 infection pwmsclassification evidence study provides class iii evidence among patients ms younger age female individuals comorbidities receiving natalizumab undergoing escalating treatment strategy receiving treatment hospital associated infected covid19 among patients ms infected covid19 severe course associated increasing age progressive form ms whereas treatment receiving interferon beta agent protectivepmid35046084 doi101212 nxi0000000000001141,0.0
astrocytederived pleiotrophin mitigates latestage autoimmune cns inflammation front immunol 2022 jan 3 12800128 doi 103389 fimmu2021800128 ecollection 2021abstractastrocytes abundant glial cells central nervous system cns capacity sense react injury inflammatory events widely documented astrocytes can exert tissuedegenerative functions less known protective diseaselimiting roles report upregulation pleiotrophin ptn mouse human astrocytes multiple sclerosis ms preclinical model experimental autoimmune encephalomyelitis eae using crisprcas9based genetic perturbation systems demonstrate vivo astrocytederived ptn critical recovery phase eae limits chronic cns inflammation ptn reduces proinflammatory signaling astrocytes microglia promotes neuronal survival following inflammatory challenge finally show intranasal administration ptn late phase eae successfully reduces disease severity making potential therapeutic candidate treatment progressive ms existing therapies limitedpmid35046956 pmcpmc8762329 doi103389 fimmu2021800128,0.0
ageperiodcohort analysis incidence multiple sclerosis twenty years lorraine france sci rep 2022 jan 19 12 1 1001 doi 101038 s41598022048365abstractmultiple sclerosis ms neurodegenerative disease central nervous system increase ms incidence time reported several regions world aimed describe evolution annual ms incidence lorraine region france 1996 2015 analyze potential components possible change temporal effect age ms onset ms onset period birth cohort overall sex cases identified relsep populationbased registry ms cases living lorraine northeastern france ms onset 1996 2015 ageperiodcohort modeling used describe trends ms incidence annual age sexstandardized incidences relatively stable 676 100 000 population 95ci 576791 1996 678 100 000 95ci 572797 2015 incidence ratio women men 24 time periods peak incidence occurred ages 25 35 years ageperiodadjusted cohort agecohortadjusted period analyses reveal period cohort effect incidence ms remained stable study period lorraine identify particular effect disease onset period birth period evolutionpmid35046460 doi101038 s41598022048365,0.0
identification key genes micrornas multiple sclerosis using bioinformatics analysis medicine baltimore 2021 dec 3 100 48 e27667 doi 101097 md0000000000027667abstractto better understand molecular mechanism underlying pathogenesis multiple sclerosis ms aimed identify key genes micrornas mirna associated ms analyze interactions differentially expressed genes degs mirnas dems based gene mirna dataset gse17846 mrna dataset gse21942 determined using r software next performed functional enrichment analysis constructed proteinprotein interaction network data validation performed ensure reliability hub genes mirnamrna regulatory network constructed total 47 dems 843 degs identified proteinprotein interaction network analysis identified several hub genes including jun fpr2 akt1 polr2l lyz cxcl8 hbb cst3 ctsz mmp9 especially lyz cxcl8 constructed mirnamrna regulatory network found hsamir1423p hsamir107 hsamir1405p hsamir613 important mirnas study reveals key genes mirnas may involved pathogenesis ms providing potential targets diagnosis treatment mspmid35049167 doi101097 md0000000000027667,0.0
lifestyle physical activity manual wheelchair users overlooked public health opportunity spinal cord 2022 jan 20 doi 101038 s4139302100729y online ahead printabstractpublic health guidelines health promotion efforts traditionally focused weekly accumulation moderate vigorous physical activity mvpa via structured exercise recent paradigm shift towards organic incorporation mvpa daily leisure nonleisure time termed lifestyle physical activity lpa however paradigm shift underlying research neglected manual wheelchair users mwcus spinal cord injury sci benefit lpa article argues expanding lpa paradigm shift research health promotion efforts involving mwcus sci suggest working definition lpa mwcus candidate metrics quantifying lpa followed brief overviews lpa correlates outcomes consequences interventions need theory based approaches study domains lastly suggest approach mitigating potential negative outcomes increased lpa mwcus suggest research agendapmid35046537 doi101038 s4139302100729y,0.0
multiple sclerosis lifnanocd4 trojan horse delivery neuroprotective biologic quot lifquot brain preclinical proof concept front med technol 2021 apr 7 3640569 doi 103389 fmedt2021640569 ecollection 2021abstractmultiple sclerosis ms demyelinating autoimmune disease attacks brain yearonyear loss brain volume starting late teens becoming manifest late twenties cure current therapies immunosuppressive lif vital stem cell growth factor active throughout lifeand essential health central nervous system cns tolerogenic myelinogenic neuroprotective nanoformulation lif lifnano using fdaapproved plga captures lifs compound therapeutic properties increasing potency 1 000fold targeted cd4 lifnanocd4 moreover circulating cd4+ lymphocytes regulated lif express treg phenotype known release t cellderived lif upon engagement cognate antigen perpetuating antigenspecific selftolerance longerterm aim treating inflammatory lesions ms asked lifnanocd4 cross bloodbrain barrier bbb measure pk pd using novel methodologies demonstrate crossing bbb show lifcargospecific antiinflammatory efficacy frontal cortex brain show safety intravenous delivery lifnanocd4 doses known provide efficacious concentrations lif cargo behind bbbpmid35047909 pmcpmc8757767 doi103389 fmedt2021640569,1.0
dimethyl fumarate reduces inflammation chronic active multiple sclerosis lesions neurol neuroimmunol neuroinflamm 2022 jan 19 9 2 e1138 doi 101212 nxi0000000000001138 print 2022 marabstractbackground objectives determine effects dimethyl fumarate dmf glatiramer acetate iron content chronic active lesions patients multiple sclerosis ms human microglia vitromethods retrospective observational study 34 patients relapsingremitting ms clinically isolated syndrome treated dmf glatiramer acetate patients lesions hyperintense rims quantitative susceptibility mapping treated dmf glatiramer acetate ga minimum 2 ontreatment scans changes susceptibility rim lesions compared among treatment groups linear mixed effects model separate vitro study induced pluripotent stem cellderived human microglia treated dmf ga treatmentinduced changes iron content activation state microglia comparedresults rim lesions patients treated dmf average 277unit reduction susceptibility per year rim lesions patients treated ga bootstrapped 95 ci 587 001 holding variables constant moreover dmf ga reduced inflammatory activation concomitantly iron content human microglia vitrodiscussion together data indicate dmfinduced reduction susceptibility ms lesions associated decreased activation state microglial cells demonstrated specific disease modifying therapy dmf decreases glial activity chronic active lesions susceptibility changes rim lesions provide vivo biomarker effect dmf microglial activityclassification evidence study provided class iii evidence dmf superior ga presence iron marker inflammation measured mri quantitative susceptibility mappingpmid35046083 doi101212 nxi0000000000001138,0.0
enrollment nonwhite participants reporting race ethnicity phase iii trials multiple sclerosis dmts systematic review neurology 2022 jan 19101212 wnl0000000000013230 doi 101212 wnl0000000000013230 online ahead printabstractbackground objectives black hispanic people ms pms found different disease courses worse outcomes associated ms compared white pms also likely negatively impacted social determinants health worsening disparities outcomes disparities may affect treatment response nonwhite pms must included trials greater generalizability research therefore inclusive treatment plans study aimed evaluate representation nonwhite groups phase iii trials approved diseasemodifying therapies dmts evolved time race ethnicity reported medical journals manufacturer websitesmethods conducted systematic review pubmed database 1995 june 2020 identify manufacturersponsored phase iii trials fdaapproved ms dmts explored race ethnicity reported trial publications using studies information available analyzed representation nonwhite pms time compared multinational census data additionally reviewed patient healthcare provider hcp facing websites available dmts assess dissemination information racial ethnic representation trialsresults 44 phase iii trial publications reviewed representing 45 trials among 17 378 report race ethnicity 14 311 reported race ethnicity proportion white participants 14 311 reported two races ethnicities compared multinational census data nonwhite pms significantly underrepresented ms trials due lack data trends representation races ethnicities assessed patient hcpfacing dmt websites reported data race ethnicity pivotal trials study results available study dashboardconclusion race ethnicity underreported ms dmt trial publications race ethnic representation omitted manufacturer websites available data show nonwhite pms significantly underrepresented ms trials availability information crucial patients together hcps make informed decisions carepmid35046135 doi101212 wnl0000000000013230,0.0
neurocoagulation mechanistic point view central nervous system semin thromb hemost 2022 jan 20 doi 101055 s00411741569 online ahead printabstractcoagulation mechanisms critical maintaining homeostasis central nervous system cns thrombin important player coagulation cascade activates protease activator receptors pars members gprotein coupled receptor family par1 located neurons glia following thrombin activation par1 signals extracellular signalregulated kinase pathway causing alterations neuronal glutamate release astrocytic morphological changes similarly anticoagulation factor activated protein c apc can cleave par1 following interaction endothelial protein c receptor thrombin apc expressed endothelial cells pericytes bloodbrain barrier bbb thrombininduced par1 activation increases cytosolic ca2+ concentration brain vessels resulting nitric oxide release increasing factin stress fibers damaging bbb integrity apc also induces par1 activation preserves bbb vascular integrity via coupling sphingosine 1 phosphate receptors thrombininduced par1 overactivation bbb disruption evident cns pathologies epileptic seizures bbb disruption promotes thrombin penetration thrombin induces par1 activation potentiates nmethyldaspartate receptors inducing glutamatemediated hyperexcitability specific par1 inhibition decreases status epilepticus severity vivo stroke elevation brain thrombin levels compromises bbb integrity direct parenchymal damage systemic factor xa inhibition improves neurological outcomes multiple sclerosis ms brain thrombin inhibitory capacity correlates clinical presentation thrombin inhibition hirudin use recombinant apc improve disease severity ms animal model review presents mechanisms underlying effects coagulation physiology pathophysiology cnspmid35052009 doi101055 s00411741569,0.0
spectral signature multiple sclerosis preliminary studies blood fraction atr ftir technique biochem biophys res commun 2022 jan 13 5934045 doi 101016 jbbrc202201046 online ahead printabstractmultiple sclerosis ms chronic neurodegenerative disease central nervous system characterized inflammation demyelination gliosis commonly known rapid accurate diagnosis ms determines treatment success standard diagnosis contains clinical symptoms observation magnetic resonance imaging mri central nervous system cns analysis cerebrospinal fluid csf nonetheless since csf sampling considered invasive individuals eligible mri decided propose diagnostic tool spectroscopy unlike lumbar puncture blood collection routine procedure regarded lowinvasive therefore used attenuated total reflectance fourier transform infrared atrftir spectroscopy technique combined chemometrics detailed spectral assay analyse blood plasma serum samples collected ms patients healthy individuals results revealed clear identification pattern ms suggesting conformation changes amide iii collagenlike proteins plasma dominance amide sheet structures changes serum spectra seem useful sample differentiationpmid35051781 doi101016 jbbrc202201046,1.0
automatic segmentation white matter hyperintensities validation comparison stateoftheart methods multiple sclerosis elderly subjects neuroimage clin 2022 jan 10 33102940 doi 101016 jnicl2022102940 online ahead printabstractdifferent types white matter hyperintensities wmh can observed mri brain spinal cord especially multiple sclerosis ms lesions patients suffering ms agerelated wmh subjects cognitive disorders elderly people better diagnose monitor disease progression quantitative evaluation wmh load proven useful clinical routine trials since manual delineation wmh segmentation highly timeconsuming suffers intra inter observer variability several methods proposed automatically segment either ms lesions agerelated wmh none validated wmh types aim proposing white matter hyperintensities automatic segmentation algorithm adapted 3d t2flair datasets whasa3d fast robust automatic segmentation tool designed implemented clinical practice detection ms lesions agerelated wmh brain using 3d t1weighted t2flair images order increase robustness ms lesions whasa3d expands original whasa method relies coupling nonlinear diffusion framework watershed parcellation regions considered wmh selected based intensity location characteristics finally refined geodesic dilation previous validation performed 2d t2flair subjects cognitive disorders elderly subjects 60 subjects heterogeneous database dementia patients multiple sclerosis patients elderly subjects multiple mri scanners wide range lesion loads used evaluate whasa whasa3d volume spatial agreement comparison consensus reference segmentations addition direct comparison ms database six available supervised unsupervised stateoftheart wmh segmentation methods lstlga lpa lesiontoads lesionbrain bianca nicmslesions default optimised settings feasible conducted whasa3d confirmed improved performance respect whasa achieving better spatial overlap dice 067 vs 063 reduced absolute volume error ave 311 vs 62 ml increased volume agreement intraclass correlation coefficient icc 096 vs 078 compared available stateoftheart algorithms ms database whasa3d outperformed unsupervised supervised methods used default settings showing highest volume agreement icc 095 well highest average dice 058 optimising retraining lstlga bianca nicmslesions using subset ms database training set resulted improved performances remaining testing set average dice lstlga default optimized 041 051 bianca default optimized 022 039 nicmslesions default optimized 017 063 whasa3d 058 evaluation comparison results suggest whasa3d reliable easytouse method automated segmentation white matter hyperintensities ms lesions agerelated wmh validation larger datasets useful confirm first findingspmid35051744 doi101016 jnicl2022102940,0.0
cerebrospinal fluid evaluation patients progressive motor impairment due critical central nervous system demyelinating lesions mult scler j exp transl clin 2022 jan 12 8 1 20552173211052159 doi 101177 20552173211052159 ecollection 2022 janmarabstractbackground elevated intrathecal immunoglobulin g igg oligoclonal bands ocbs igg people progressive motor impairment due critical demyelinating lesions uncertain significanceobjective compare clinical radiological features people critical demyelinating lesioninduced progressive motor impairment without elevated intrathecal igg synthesismethods total 133 people progressive motor impairment attributable critical demyelinating lesions corticospinal tract location consistent progressive motor deficit compared regarding clinical radiological presentation without 2 unique cerebrospinal fluid csf ocb igg index 085results ninetyeight 74 csfelevated ocb igg index higher increased magnetic resonance imaginglesion burden differences found without csf abnormalities sex 46 98 female 47 vs 22 35 63 p 011 onsetage median 49 vs 50 years p 05 progression onset 62 98 63 vs 25 35 71 progression postrelapse 36 98 37 vs 10 35 29 p 04 duration demyelinating disease onset csf examination 30 0359 vs 48 0323 months p 07 critical lesions radiologically similar commonly cervical spine located 72 98 74 vs 19 35 54 p 018 without csf abnormalitiesconclusions people critical demyelinating lesioninduced progressive motor impairment typically elevated intrathecal igg ocb igg similar clinical radiological presentation regardless csf findings therefore representing valid presentations progressive demyelinating diseasepmid35047187 pmcpmc8761886 doi101177 20552173211052159,1.0
informationseeking strategies people multiple sclerosis spain infoseekms study patient prefer adherence 2022 jan 11 165160 doi 102147 ppas344690 ecollection 2022abstractpurpose patients multiple sclerosis ms increasingly demanding access reliable information regarding disease objective infoseekms study assess strategies people ms use searching information disease including sources frequency reliability preferred contentpatients methods noninterventional crosssectional study conducted patients diagnosis ms according 2010 mcdonald criteria included infoseek questionnaire used assess patients strategies seeking information disease clinical characteristics variables including disability quality life fatigue cognition anxiety depression analysed using expanded disability status scale edss multiple sclerosis impact scale msis29 5item modified fatigue scale mfis5 symbol digit modalities test sdmt hospital anxiety depression scale hads respectivelyresults three hundred two patients studied mean age 423 10 years 64 female mean disease duration 96 70 years 90 relapsingremitting ms mean edss score 26 19 internet either via mobile computer frequently reported source information lifestylerelated information 672 research emerging treatments 636 symptom control 497 sharing experiences patients 464 disease prognosis 464 searched topics neurologists nurses trusted source information younger patients higher sdmt scores associated search resources m 377 m 4997 respectively frequency searches related number relapses r2 007 edss r2 014 msis29 physical psychological components r2 0132 inversely depression r2 0132 conclusion although healthcare professionals considered reliable source information people ms searching information internet frequent individualized information strategy considering different factors involved neededpmid35046641 pmcpmc8762518 doi102147 ppas344690,0.0
vitro models bloodbrain barrier tools translational medicine front med technol 2021 feb 15 2623950 doi 103389 fmedt2020623950 ecollection 2020abstractmedical progress historically depended scientific discoveries recently science driven technological advancements translated clinic fostered new treatments interventions recently technologydriven medical progress often outpaced laboratory research example intravascular devices pacemakers heart brain spinal cord stimulators surgical robots used routinely treat variety diseases rapid expansion science ever advanced molecular genetic mechanisms disease often distanced laboratorybased research daytoday clinical realities remain based evidence outcomes recognized reason hiatus lack laboratory tools recapitulate clinical reality faced physicians surgeons overcome nih fda recent past joined forces support development humanonachip will allow research scientists perform experiments realistic replica testing effectiveness novel experimental therapies development humanonachip rests capacity grow vitro various organsonachip connected appropriate vascular supplies nerves ability measure perform experiments virtually invisible organs one tissue structures scaled chip human bloodbrain barrier review gives historical perspective vitro models bbb summarizes recent 3d models attempt fill gap research modeling patient care also present summary vitro models bbb can applied study human brain diseases treatments chosen neuroaids covid19 multiple sclerosis alzheimers disease examples vitro model application neurological disorders major insight pertaining illnesses consequence profound understanding bbb can reveal new avenues development diagnostics efficient therapies definitive clarity disease etiology pathological progressionpmid35047899 pmcpmc8757867 doi103389 fmedt2020623950,0.0
prognosis second clinical event baseline mri patients cis multicenter study using machine learning approach neuroradiology 2022 jan 20 doi 101007 s00234021028857 online ahead printabstractpurpose predict occurrence second clinical event patients cis suggestive ms baseline magnetic resonance imaging mri means pattern recognition approachmethods two hundred sixtysix patients cis recruited four participating centers followup 3 years 130 patients second clinical episode 136 grey matter white matter t1hypointensities masks segmented 3d t1weighted images acquired 3 t scanners used features classification approach differences cis remained cis developed second event assessed global level regional level arranging regions according contribution classification modelresults classification metrics around even 50 global regional approaches accuracies change t1hypointensity maps added model just specificity increased 80 among 30 regions largest contribution 26 grey matter 4 white matter regions grey matter regions contributing showed either larger smaller volume group patients remained cis compared second event volume t1hypointensities always larger group presented second eventconclusions prediction second clinical event cis patients baseline mri seems present highly heterogeneous pattern leading low classification accuracies adding t1hypointensity maps seem improve accuracy classification modelpmid35048162 doi101007 s00234021028857,0.0
corpus callosum volumetrics clinical progression early multiple sclerosis eur rev med pharmacol sci 2022 jan 26 1 225231 doi 1026355 eurrev_202201_27772abstractobjective corpus callosum cc commonly affected multiple sclerosis ms known association cc atrophy ms clinical activity study assessed association callosal atrophy lesions volume residual cc volume clinical disability early ms patientssubjects methods thirteen ms subjects 9 female mean age 369 years studied magnetic resonance imaging mri selected mri scans performed baseline t0 6 t1 12 t2 24 months t3 baseline cc segmented three sections genu body splenium callosal boundaries outlined cc lesions manually traced normal cc cc lesion volumes measured using semiautomatic softwareresults january 2014 december 2016 selected patients confluent lesions mri t3 significant increase size confluent lesions compared baseline p00007 t1 significant increase size confluent p002 single lesions located callosal body p004 detected patients edss 15 also cc residual volume ccr rather whole cc volume ccv significantly correlated p003 clinical progression ms whole cohortconclusions early ms patients higher edss baseline significant increase confluent cc lesions size evident particularly callosal body also median ccr significantly associated ms progression whole ms group regardless initial edss given significant association disability encourage measuring cc body lesions residual cc size therapeutic decisions prognostic planning early mspmid35048999 doi1026355 eurrev_202201_27772,0.0
contribution rare lowfrequency variants multiple sclerosis susceptibility italian continental population front genet 2022 jan 3 12800262 doi 103389 fgene2021800262 ecollection 2021abstractgenomewide association studies identified 200 risk loci multiple sclerosis ms focusing common variants account 50 disease heritability goal study investigate whether lowfrequency rare functional variants located msestablished associated loci may contribute disease risk relatively homogeneous population testing cumulative effect burden genewise tests sequenced 98 genes 588 italian patients ms 408 matched healthy controls hcs variants selected using different filtering criteria based allelic frequency silico functional impacts genes showing significant burden n 17 sequenced independent cohort 504 ms 504 hc highest signal cohorts observed disruptive variants stopgain stoploss splicing variants located efcab13 gene coding protein unknown function p 104 among variants minor allele stopgain variant showed significantly higher frequency ms versus hc sequenced cohorts p 00093 p 0025 confirmed metaanalysis third independent cohort 1298 ms 1430 hc p 0001 assayed snp array realtime pcr 14 heterozygous individuals variant evidence presence stopgain allele suggesting transcript degradation nonsense mediated decay supported evidence carriers stopgain variant lower expression gene p 00184 conclusion identified novel lowfrequency functional variant associated ms susceptibility suggesting possible role rare lowfrequency variants ms reported complex diseasespmid35047017 pmcpmc8762330 doi103389 fgene2021800262,0.0
case report gallbladder agenesis novelty still laparoscopic surprise cureus 2021 dec 14 13 12 e20401 doi 107759 cureus20401 ecollection 2021 decabstractgallbladder agenesis ga rare embryological anomaly presents acute cholecystitis likesymptoms often incidental finding diagnosed surgery reported case ga patient presented dyspepsia acute right upper abdomen pain ultrasonographic signs acute lithiasic cholecystitis preoperative assessment according firstlevel exams oriented diagnosis acute lithiasic cholecystitis atrophy sclerosis laparoscopy proximal transverse colon found strictly adherent gallbladder fossa gallbladder found absent surgical procedure consisted lysis multiple colohepatic adhesions diagnosis congenital ga made laparoscopically postoperative radiological images based ct mr examinations documented diagnosis ga biliary duct anatomical variant recovery uneventful patient remained symptomfree four years ga clinical challenge still poses diagnostic therapeutic dilemmas although diagnostic therapeutic algorithm accepted worldwide due heterogeneity clinical scenarios variability hospital facilities surgeons familiar rare entity conversion laparotomy unnecessary operative procedures avoided operative settingpmid35047247 pmcpmc8756331 doi107759 cureus20401,0.0
impaired pharyngeal reflex responses negative pressure novel cause sleep apnea multiple sclerosis j appl physiol 1985 2022 jan 20 doi 101152 japplphysiol002402021 online ahead printabstractobstructive sleep apnea osa common people multiple sclerosis ms however people ms often typical anatomical risk factors ie nonobese female predominance accordingly nonanatomical factors impaired upper airway muscle function may particularly important osa pathogenesis ms therefore study aimed investigate genioglossus largest upperairway dilator muscle reflex responses brief pulses upper airway negative pressure people osa ms 11 people ms osa 10 osa controls without ms matched age sex osa severity fitted nasal mask pneumotachograph choanal epiglottic pressure sensors intramuscular electrodes genioglossus approximately 60 brief 250ms negative pressure pulses 12cmh2o mask pressure delivered every 26 breaths random quiet nasal breathing wakefulness determine genioglossus emg reflex responses timing amplitude morphology available recent clinical mri brain scans evaluated number size location brainstem lesions ms group present genioglossus reflex excitation responses similar ms participants controls eg peak excitation amplitude 22985 vs 28298 baseline p017 however 30 people ms either abnormal predominantly inhibition protective excitation reflex participants ms without reflex multiple brainstem lesions including hypoglossal motor nucleus may impair sensory processing efferent output impaired pharyngeal reflex function may important contributor osa pathogenesis proportion people mspmid35050793 doi101152 japplphysiol002402021,0.0
extracellular vesicles adiposederived stem cells promote microglia m2 polarization neurological recovery mouse model transient middle cerebral artery occlusion background adiposederived stem cells adscs extracellular vesicles evs therapeutic potential ischemic brain injury underlying mechanism poorly understood current study aimed explore contribution mirnas adscevs treatment cerebral ischemiamethodsafter intravenous injection adscevs therapeutic efficacy evaluated neurobehavioral tests brain atrophy volume polarization microglia assessed immunostaining qpcr performed mirna sequencing adscevs analyzed relationship upregulated mirnas adscevs microglial polarizationrelated proteins using ingenuity pathway analysis ipa resultsthe results showed adscevs reduced brain atrophy volume improved neuromotor cognitive functions mouse ischemic stroke loss oligodendrocytes attenuated adscevs injection number blood vessels well newly proliferated endothelial cells periischemia area higher adscevs treated group pbs group addition adscevs regulated polarization microglia resulting increased repairpromoting m2 phenotype decreased proinflammatory m1 phenotype finally stat1 pten highlighted two downstream targets upregulated mirnas adscevs among 85 microglia macrophage polarization related proteins ipa inhibition stat1 pten adscevs confirmed cultured microgliaconclusionsin summary adscevs reduced ischemic brain injury associated regulation microglial polarization mirnas adscevs partly contributed function regulating microglial polarization targeting pten stat1,0.0
twodimensional measurements cutoff values useful assessing brain volume physical disability processing speed multiple sclerosis abstractbackground twodimensional 2d measures proposed potential proxy measures wholebrain volume multiple sclerosis ms however cutoff values determine degree brain volume loss bvl established since previously developed system categorize ms patients clusters significantly different degrees bvl tried identify cutoff values 2d measurements can discriminate ms patients basis disease severity associated brain atrophymethods crosssectional analysis ninetyone consecutive japanese ms patientsclinically isolated syndrome 5 relapsingremitting ms 78 progressive ms 17 categorized two clusters cl1 cl2 significantly different degree bvl using method described previous study ms patients also evaluated 2d measurements namely third ventricle width lateral ventricle width lvw bicaudate ratio bcr corpus callosum index cci thereafter performed receiver operating characteristic analysis determine cutoff values 2d measurements categorizing ms patients two clustersresults identified optimal cutoff values 2d measure high specificity sensitivity cutoff values lvw bcr cci divided ms patients two subgroups wholebrain grey matter volume edss processing speed significantly differentconclusion lvw bcr cci particular cutoff values useful discriminate ms patients decreased brain volume physical disability processing speed,0.0
effect interventions anticipated improve plantar intrinsic foot muscle strength fallrelated dynamic function adults systematic review background plantar intrinsic foot muscles pifms role dynamic functions balance propulsion vital walking muscles atrophy older adults therefore population high risk falling may benefit strengthening muscles order improve retain gait performance therefore aim provide insight evidence effect interventions anticipated improve pifm strength dynamic balance control foot function gait adultsmethodsa systematic literature search performed five electronic databases eligibility peerreviewed papers published january 1 2010 july 8 2020 reporting controlled trials prepost interventional studies assessed two reviewers independently results moderate highquality studies extracted data synthesis summarizing standardized mean differences smd grade approach used assess certainty evidenceresultsscreening 9199 records resulted inclusion 11 articles five included data synthesis included studies mainly performed younger populations lowcertainty evidence revealed beneficial effect pifm strengthening exercises vertical ground reaction force smd 031037 lowcertainty evidence showed pifm strength training improved performance dynamic balance testing smd 041143 evidence effect pifm strengthening exercises medial longitudinal foot arch kinematicsconclusionsthis review revealed best lowcertainty evidence pifm strengthening exercises improve foot function gait lowcertainty evidence favorable effect dynamic balance control need highquality studies aim investigate effect functional pifm strengthening exercises large samples older adults outcome measures related fall risk role pifms propulsive forces balance locomotion addition pifm strength measures,0.0
cerebrospinal fluid findings covid19 multicenter study 150 lumbar punctures 127 patients background comprehensive data cerebrospinal fluid csf profile patients covid19 neurological involvement largescale multicenter studies missing farobjectiveto analyze systematically csf profile covid19methodsretrospective analysis 150 lumbar punctures 127 patients pcrproven covid19 neurological symptoms seen 17 european university centersresultsthe frequent pathological finding bloodcsf barrier bcb dysfunction median qalb 114 672508 present 58 116 50 samples patients without pre coexisting cns diseases group qalb remained elevated 14d 476 even 30d 556 neurological onset csf total protein elevated 54 118 458 samples median 6535 mg dl 4532404 strongly correlated qalb csf white cell count wcc increased 14 128 11 samples mostly lymphomonocytic median 10 cells l 100 4 albuminocytological dissociation acd found 43 115 374 samples csf llactate increased 26 109 24 median 304 mmol l 224 csfigg elevated 50 100 50 peripheral origin since qigg normal almost cases qiga qigm 58 103 samples 56 pattern 4 oligoclonal bands ocb compatible systemic inflammation present csfrestricted ocb found 2 103 19 sarscov2csfpcr negative 76 76 samples routine csf findings normal 35 cytokine levels frequently elevated csf often associated bcb dysfunction serum partly remaining positive high levels weeks months 939 tests note positive sarscov2iggantibody index ai found 2 19 105 patients associated unusually high wcc strongly increased interleukin6 il6 index one tested antineuronal antiglial autoantibodies mostly absent csf serum 1509 tests samples patients pre coexisting cns disorders group ii n 19 including multiple sclerosis jcvirusassociated immune reconstitution inflammatory syndrome hsv vzv encephalitis meningitis cns lymphoma antiyo syndrome subarachnoid hemorrhage csf findings mostly representative respective diseaseconclusionsthe csf profile covid19 neurological symptoms mainly characterized bcb disruption absence intrathecal inflammation compatible cerebrospinal endotheliopathy persistent bcb dysfunction elevated cytokine levels may contribute acute symptoms long covid direct infection cns sarscov2 occurring seems rare broad differential diagnostic considerations recommended avoid misinterpretation treatable coexisting neurological disorders complications covid19,0.0
diagnostic criteria acute headache attributed ischemic stroke sentinel headache ischemic stroke background defining relationship headache stroke essential current diagnostic criteria ichd3 acute headache attributed ischemic stroke based primarily opinion experts rather published clinical evidence based extensive casecontrol studies patients firstever stroke diagnostic criteria sentinel headache ischemic stroke exist present study aimed develop explicit diagnostic criteria headache attributed ischemic stroke sentinel headachemethodsthis prospective casecontrol study included 550 patients mean age 631 54 males firstever ischemic stroke 192 control patients mean age 587 36 males admitted emergency room without acute neurological deficits severe disorders standardized semistructured interview forms used evaluate past present headaches facetoface interviews neurologist admission emergency room groups patients headaches diagnosed according ichd3 tabulated onset different headaches firstever ischemic stroke time onset stroke divided three groups new type headache previous headache altered characteristics previous unaltered headaches done headaches control patients within one week admission hospital time entry data used create test diagnostic criteria acute headache attributed stroke sentinel headacheresultsour previous studies showed headache onset ischemic stroke present 82 149 550 patients 81 147 patients sentinel headache within last week stroke 60 headaches stroke onset fulfilled diagnostic criteria ichd3 therefore proposed alternative criteria sensitivity 100 specificity 97 besides developed diagnostic criteria sentinel headache first time specificity 98 sensitivity 100conclusionswe suggest alternative diagnostic criteria acute headache attributed ischemic stroke new diagnostic criteria sentinel headache high sensitivity specificity,0.0
serum molecular biomarkers neuromyelitis optica multiple sclerosis abstractbackgroundneuromyelitis optica spectrum disorder nmosd rare severe inflammatory demyelinating disorder central nervous system cns mainly affects optic nerves spinal cord aims study determine whether expression levels serological cytokines distinguish 1 nmosd healthy controls hcs 2 nmosd patients without aquaporin4 aqp4 antibody biomarker 3 nmosd patients without antibody aqp4 ms patientsmethodsthe expression levels 200 proteins serum 41 nmosd 32 antibodies aqp4 9 without antibodies aqp4 12 ms patients 34 hcs measured using glassbased antibody arrays none patients received immunosuppressive treatment parallel correlation protein expression nmosd ms patients clinical traits determined weighted gene coexpression network analysis wgcna resultsthirtynine serological proteins differentially expressed nmosd patients compared hcs 29 proteins observed ms patients addition data reveal 15 differentiallyexpression proteins deps aqp4igg seronegative aqp4igg seropositive nmosd patients 9 deps nmosd ms patients aqp4iggconclusionserological il17b significantly upregulated nmosd ms patients compared hcs key biomarker nmosd ms serological vegf mpif1 nrcam positively associated aqp4igg titer also demonstrate egf may involved breakdown bbb downregulating claudin5,1.0
dosedependent effect myelin oligodendrocyte glycoprotein visual function optic nerve damage experimental autoimmune encephalomyelitis j neurosci res 2022 jan 18 doi 101002 jnr25007 online ahead printabstractfemale dark agouti rats immunized increasing doses myelin oligodendrocyte glycoprotein mog develop experimental autoimmune encephalomyelitis eae preclinical model multiple sclerosis typical eae motor impairments assessed daily noninvasive visual evoked potentials veps recorded baseline 5 weeks immunization final histopathology optic nerves ons immunized rats exhibited relapsingremitting clinical course vep histological abnormalities detected mog dosedependent gradient increasing mog dosage augmented visual function impairment eae monitored vep recording assess demyelination axonal loss along onspmid35043454 doi101002 jnr25007,1.0
relationship presence spinal cord lesion restless legs syndrome multiple sclerosis somatosens mot res 2022 jan 1815 doi 101080 0899022020222027360 online ahead printabstractbackground even though prevalence restless leg syndrome multiple sclerosis ms known vary 125 60 underlying pathophysiological mechanism remains unclearaim study aims investigate relationship spinal cord lesions restless leg syndrome msmaterials methods total 959 persons ms enrolled study demographic clinical data persons ms recorded interviewing medical records neurologists blind presence restless leg syndrome evaluated mri scans presence demyelinating lesions brainstem spinal cordresults restless leg syndrome detected 222 participants 2315 restless leg syndrome significantly linked mean age body mass index gender ms duration persons ms restless leg syndrome higher disability level p 0044 addition difference brainstem thoracic cord found persons ms without restless leg syndrome significant relationship presence cervical cord lesion restless leg syndromeconclusion higher disability scores characteristics lesion patterns spinal cord explain higher rates restless leg syndrome persons ms considering negative effects restless leg syndrome increased awareness treatment restless leg syndrome among persons ms essential better managingpmid35042439 doi101080 0899022020222027360,1.0
updated review epigeneticrelated mechanisms contribution multiple sclerosis disease cns neurol disord drug targets 2022 jan 19 doi 102174 1871527321666220119104649 online ahead printabstractmultiple sclerosis ms multifactorial neurodegenerative inflammatory demyelination disease incomplete remyelination cns informative reveal underlying molecular mechanisms ms molecular mechanisms involving epigenetic changes play pivotal role disease epigenetic changes impact gene expression without altering underlying dna sequence main epigenetic modifications play key role regulation gene expression principally include dna methylation histone modifications micrornaassociated posttranscriptional gene silencing review summarize dynamics epigenetic changes relation environmental risk factors ms pathogenesis studies suggest epigenetic changes role development ms environmental risk factors vitamin d smoking epsteinbarr virus infection seem influence development susceptibility ms investigating epigenetic environmental factors can provide new opportunities molecular basis diseases shows complicated pathogenesis epigenetic research potential complete understanding ms initiation progression increasing knowledge molecular mechanisms ms sheds light new insights potential ms treatments however need vivo evaluation role epigenetic factors ms therapy valuable indicate role various epigenetic factors mspmid35043771 doi102174 1871527321666220119104649,1.0
edaravone attenuates disease severity experimental autoimmune encephalomyelitis increases gene expression nrf2 ho1 physiol res 2022 jan 19 online ahead printabstractthe aim study evaluate therapeutic potential edaravone murine model multiple sclerosis experimental autoimmune encephalomyelitis eae expand knowledge mechanism action edaravone 6 mg kg day administered intraperitoneally onset clinical symptoms end experiment 28 days disease progression assessed daily using severity scores peak disease histological analyses markers oxidative stress os parameters mitochondrial function brains spinal cords sc mice determined gene expression inducible nitric oxide synthase inos nuclear factor erythroid 2related factor 2 nrf2 heme oxygenase1 ho1 peroxisome proliferatoractivated receptorgamma coactivator pgc 1alpha determined end experiment edaravone treatment ameliorated eae severity attenuated inflammation sc eae mice verified histological analysis moreover edaravone treatment decreased os increased gene expression nrf2 ho1 increased activity mitochondrial complex ii iii reduced activity mitochondrial complex iv preserved atp production sc eae mice conclusion findings study provide additional evidence edaravone potential treatment multiple sclerosis expand knowledge mechanism action edaravone eae modelpmid35043649,0.0
selfinjectable dmts relapsing ms neda assessment 10 years realworld cohort acta neurol scand 2022 jan 19 doi 101111 ane13582 online ahead printabstractbackground multiple sclerosis ms immunemediated disorder central nervous system dmts effectively reduce annual relapse ratethus reducing disease activityand lesser extent dmts prevent disease progression people ms monitoring efficacy dmts evidence disease activity neda provides objective perspective evaluating treatment successobjective goal detect prevalence neda3 people ms treated selfinjectable dmts two years 10 years retrospective studymethods treatment continuation rates neda3 parameters 2nd 10th years evaluatedresults total 1032 patients diagnosed rrms included study 613 patients 593 continued treatment 10 years first two years neda3 detected 321 patients 524 112 613 patients continued selfinjectable dmts end 10 years 183 rate neda3 patients starting treatment age 35 151 compared patient group starting treatment aged 34 less 202 p 004 conclusion study includes comprehensive neda3 data real world evidence supports idea neda3 can effective early predictor progressionfree status treatment followup 10 yearspmid35043388 doi101111 ane13582,0.0
cognitive composites genetic frontotemporal dementia genficog background clinical endpoints upcoming therapeutic trials frontotemporal dementia ftd increasingly urgent cognitive composite scores often used endpoints lacking genetic ftd aimed create cognitive composite scores genetic frontotemporal dementia ftd well recommendations recruitment duration clinical trial designmethodsa standardized neuropsychological test battery covering six cognitive domains completed 69 c9orf72 41 grn 28 mapt mutation carriers cdr plus naccftld 05 275 controls logistic regression used identify combination tests distinguished best mutation carrier group controls composite scores calculated weighted averages test scores models based regression coefficients sample size estimates calculated individual cognitive tests composites theoretical trial aimed preventing progression prodromal stage cdr plus naccftld 05 fully symptomatic stage cdr plus naccftld 1 timetoevent analysis performed determine quickly mutation carriers progressed cdr plus naccftld 05 1 therefore long trial need resultsthe results logistic regression analyses resulted different composite scores mutation carrier group ie c9orf72 grn mapt estimated sample size detect treatment effect lower composite scores individual tests kaplanmeier curve showed 3 years 50 individuals converted cdr plus naccftld 05 1 means estimated effect size needs halved sample size calculations half mutation carriers expected progress cdr plus nacc ftld 05 1 without treatment time perioddiscussionwe created genespecific cognitive composite scores c9orf72 grn mapt mutation carriers resulted substantially lower estimated sample sizes detect treatment effect individual cognitive tests genficog composites potential cognitive endpoints upcoming clinical trials results study provide recommendations estimating sample size trial duration,0.0
functional characterisation amyotrophic lateral sclerosis risk locus gpx3#x2f tnip1 background amyotrophic lateral sclerosis als complex lateonset neurodegenerative disease genetic contribution disease liability genomewide association studies gwas identified ten risk loci date including tnip1 gpx3 locus chromosome five given association analysis data alone determine plausible risk gene locus undertook comprehensive suite silico vivo vitro studies address thismethodsthe functional mapping annotation fuma pipeline five tools conditional joint analysis gctacojo stratified linkage disequilibrium score regression sldsc polygenic priority scoring pops summarybased mendelian randomisation smrheidi transcriptomewide association study twas analyses used perform bioinformatic integration gwas data ncases 20 806 ncontrols 59 804 omics reference datasets including blood eqtlgen consortium n 31 684 brain n 2581 followed specific expression studies als casecontrol cohorts microarray ntotal 942 protein ntotal 300 gene knockdown kd studies human neuronal ipsc cells zebrafishmorpholinos mo resultssmr analyses implicated tnip1 gpx3 p 115 106 simple snp expression relationship integrating multiple datasets using pops supported gpx3 tnip1 vivo expression analyses blood als cases identified lower gpx3 expression correlated progressed disease als functional rating score p 55 103 adjusted r2 0042 beffect 274 133 ng ml alsfrs unit microarray protein data suggesting lower expression risk allele recessive model p 006 p 002 respectively validation vivo indicated gpx3 kd caused significant motor deficits zebrafishmo mean difference vs control 95 ci vs control swim distance 112 28 mm time 129 059 s speed 320 253 mm s respectively p 00001 rescued gpx3 expression phenotype identified tnip1 kd gpx3 overexpressionconclusionsthese results support gpx3 lead als risk gene locus data needed confirm reject role tnip1 implications understanding disease mechanisms gpx3 acts pathway sod1 wellestablished alsassociated gene identifying new therapeutic approaches previous examples indepth investigations risk loci als exist similar approach applied investigate future expected gwas findings,0.0
characterizing memory t helper cells patients psoriasis subclinical early psoriatic arthritis using machine learning algorithm background psoriasis patients developing psoriatic arthritis psa thought go different phases understanding underlying events phases crucial diagnose psa early characterized circulating memory t helper th cells psoriasis patients without arthralgia psoriasis patients developed psa followup subclinical psa early psa patients healthy controls elucidate role psa developmentmethodswe used peripheral blood mononuclear cells sex agematched psoriasis patients included rotterdam joint skin study n22 early psa patients included dutch south west early psoriatic arthritis cohort depar n23 healthy controls hc n17 profiled memory th cell subsets flow cytometry used machine learning algorithm flowsom interpret dataresultsthree 22 psoriasis patients developed psa 2year followup flowsom identified 12 clusters memory th cells including th1 th2 th17 22 th171 cells psoriasis psa patients higher numbers th17 22 healthy controls psoriasis patients without arthralgia lower numbers ccr6ccr4+cxcr3+ memory th cells higher numbers ccr6+ccr4cxcr3memory th cells compared hc psa patients higher numbers th2 cells ccr6+ccr4+cxcr3 cells lower numbers ccr6+ccr4+cxcr3+ memory th cells compared hc number ccr6+ th171 cells negatively correlated tender joint counts number ccr6+ th17 cells positively correlated skin disease severityconclusionsunsupervised clustering analysis revealed differences circulating memory th cells psoriasis psa patients compared hc however specific subset identified characterizing subclinical psa patients,0.0
development geras dancing cognition exercise dance feasibility study background dance mindbody activity purposeful rhythmic movement music growing interest using dance form cognitive physical rehabilitation manuscript describes development geras dancing cognition exercise dance evaluates feasibility older adults cognitive mobility impairmentsmethodsthe progressive dance curricula delivered 15 weeks 1h class twice weekly participants eligible communitydwelling older adults aged 60+ early cognitive mobility impairment able follow threestep commands move independently feasibility outcomes included recruitment retention adherence participant satisfaction safety adverse eventsresultstwentyfive older adults mean standard deviation sd age 7755 610 years range 6890 years early cognitive montreal cognitive assessment score sd 2177 405 mobility 92 prefrail frail indicated fried frailty phenotype impairments recruited geriatric outpatient clinic within community total 20 25 80 participants completed study average class attendance 72 selfreported homework adherence mostdays every day 89 stepwise progression dance curricula observed increases motor complexity balance demands 95 participants rated program justright challenge ninety percent participants rated geras dance excellent 100 recommend program friend family member 50 participants connected outside class time selfinitiated coffee club adverse events falls fractures reported 2 participants occurred home unrelated dance intervention study period predetermined thresholds feasibility met outcomesdiscussiongeras dance feasible enjoyable program older adults early cognitive mobility impairments geras dance curriculum grading duration sequence instructions motor complexity increases agility balance coordination appear appropriately tailored population future work will explore feasibility geras dance new settings ie virtually online community centers retirement homes mindbodysocial benefits dance,0.0
axon guidance molecules immunometabolic diseases abstractthe global prevalence metabolic diseases obesity diabetes atherosclerosis rapidly increasing now reached epidemic proportions chronic tissue inflammation characteristic metabolic diseases indicating immune responses closely involved pathogenesis metabolic disorders however regulatory mechanisms underlying immunometabolic crosstalk diseases completely understood recent studies revealed multifaceted functions semaphorins originally identified axon guidance molecules regulating tissue inflammation metabolic disorders thereby highlighting functional coupling semaphorin signaling immunometabolism review explore semaphorin signaling transcends beyond merely guiding axons controlling immune responses metabolic diseases,0.0
revealing potential diagnostic gene biomarkers septic shock based machine learning analysis background sepsis inflammatory response caused infection pathogenic microorganisms body shock caused called septic shock view aimed identify potential diagnostic gene biomarkers diseasematerial methodsfirstly mrnas expression data sets septic shock retrieved downloaded geo gene expression omnibus database differential expression analysis functional enrichment analysis used identify biological function demrnas differentially expressed mrnas machine learning analysis used determine diagnostic gene biomarkers septic shock thirdly rtpcr realtime polymerase chain reaction verification performed lastly gse65682 data set utilized perform diagnostic prognostic analysis identified superlative diagnostic gene biomarkersresultsa total 843 demrnas including 458 upregulated 385 downregulated demrnas obtained septic shock 15 superlative diagnostic gene biomarkers rab13 kif1b clec5a fcer1a cacna2d3 dusp3 hmgn3 mgst1 arhgef18 septic shock identified machine learning analysis rf random forests svm support vector machine dt decision tree models used construct classification models accuracy dt svm rf models high interestingly rf model highest accuracy worth mentioning arhgef18 fcer1a related survival cacna2d3 dusp3 participated mapk signaling pathway regulate septic shockconclusionidentified diagnostic gene biomarkers may helpful diagnosis therapy patients septic shock,0.0
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metabolomics promising tool improving understanding multiple sclerosis review recent advances biomed j 2022 jan 15s23194170 22 00004x doi 101016 jbj202201004 online ahead printabstractmultiple sclerosis ms inflammatory demyelinating disease central nervous system usually affects young adults development ms closely related changes metabolome metabolomics studies performed using biofluids tissue samples rodent models human patients reveal metabolic alterations associated ms progression review aims provide overview applications metabolomics investigations perturbed metabolic pathways ms reveal potential metabolomics personalizing treatments conclusion informative variations metabolites can potential biomarkers advancing understanding ms pathogenesis ms diagnosis predicting progression disease estimating drug effects metabolomics will promising technique improving clinical care mspmid35042018 doi101016 jbj202201004,1.0
optimization novel piperazinone series potent selective peripheral covalent btk inhibitors bioorg med chem lett 2022 jan 15128549 doi 101016 jbmcl2022128549 online ahead printabstractbtk tyrosine kinase playing important role b cell myeloid cell functions b cell receptor bcr signaling fc receptor fcr signaling selective inhibition btk potential provide therapeutical benefits patients suffering autoimmune diseases report design optimization characterization novel potent highly selective covalent btk inhibitors starting piperazinone hit derived selective reversible inhibitor solved whole blood cellular potency issue introducing electrophilic warhead reach cys481 design led covalent irreversible btk inhibitor series excellent kinase selectivity well excellent cd69 cellular potency optimization metabolic stability led representative compound like 42 demonstrated strong cellular potency based btk target occupancy inhibition bcell proliferation readouts proximal distal functional activitypmid35041943 doi101016 jbmcl2022128549,0.0
potentially modifiable associates anxiety people multiple sclerosis systematic review disabil rehabil 2022 jan 18112 doi 101080 0963828820212022776 online ahead printabstractpurpose high percentage people multiple sclerosis pwms experience anxiety can negatively impact quality life despite anxiety pwms remains researched review aims identify associates anxiety pwms amenable change view informing development interventions areamaterials methods following databases searched studies investigating anxiety pwms 2015 2021 psycinfo pubmed embase web science search consisted keywords relating ms fear anxiety worry screening completed two reviewers narrative synthesis used analyze data mmat used quality appraisalresults 3117 unique abstracts screened 39 studies met criteria inclusion evidence found linking anxiety pwms several modifiable factors broadly categorized either psychological social lifestyle factors perceptions self ones ability cope adjust ms emerged important psychological factors physical activity social support friends also linked improved anxiety outcomesconclusions anxiety pwms linked number modifiable factors findings may help inform development rehabilitation interventions decrease anxiety msimplications rehabilitationthis review highlights interventions successfully lowered anxiety people ms pwms however clear need development interventions target pathologically specific concerns surrounding anxiety populationwe show number factors amenable change associate anxiety suggesting factors may appropriate targets anxiety interventions pwmsenhancing physical activity selfefficacy important means healthcare professionals can reduce anxiety msidentifying ways encouraging positive coping increasing social support targets improving comorbid anxiety pwmsfocusing modifiable factors highlighted offers considerable potential enhancing psychological wellbeing grouppmid35040719 doi101080 0963828820212022776,0.0
progranulin therapeutic target neurodegenerative diseases trends pharmacol sci 2022 jan 15s01656147 21 002327 doi 101016 jtips202111015 online ahead printabstractprogranulin pgrn encoded grn gene plays key role development survival function maintenance neurons microglia mammalian brain regulates lysosomal biogenesis inflammation repair stress response aging grn lossoffunction mutations cause neuronal ceroid lipofuscinosis frontotemporal dementiagrn ftdgrn gene dosagedependent manner mutations reduce pgrn levels increase risk developing alzheimers disease parkinsons disease limbicpredominant agerelated transactivation response dnabinding protein 43 encephalopathy well exacerbate progression amyotrophic lateral sclerosis als ftd caused hexanucleotide repeat expansion c9orf72 gene elevating restoring pgrn levels attractive therapeutic strategy investigated neurodegenerative diseases multiple mechanisms actionpmid35039149 doi101016 jtips202111015,0.0
development population pharmacokinetic model diroximel fumarate metabolites monomethyl fumarate 2hydroxyethyl succinimide following oral administration diroximel fumarate healthy participants patients multiple sclerosis neurol ther 2022 jan 18 doi 101007 s40120021003166 online ahead printabstractintroduction diroximel fumarate drf nextgeneration oral fumarate indicated usa relapsing forms multiple sclerosis ms joint population pharmacokinetic model developed major active metabolite monomethyl fumarate mmf major inactive metabolite 2hydroxyethyl succinimide hes drfmethods mmf hes data included 341 healthy volunteers 48 patients ms across 11 phase iii studies drf administered single multiple doses population modeling performed nonmem version 73 firstorder conditional estimation methodresults estimated mmf clearance clmmf volume distribution absorption rate constant ka 135 l h 304 l 504 h1 respectively clmmf hes clearance clhes increased increasing body weight clhes decreased decreasing renal function clmmf clhes 28 12 lower patients ms healthy volunteers respectively ka reduced presence low medium highfat meals 37 51 67 respectively mmf 34 49 62 respectively hesconclusions age sex race baseline liver function parameters total bilirubin albumin aspartate aminotransferase considered significant predictors mmf hes dispositionpmid35041178 doi101007 s40120021003166,0.0
ictal onset stereoelectroencephalography patterns temporal lobe epilepsy type distribution prognostic value acta neurochir wien 2022 jan 18 doi 101007 s0070102205122z online ahead printabstractobjective aim study investigate different ictal onset stereoelectroencephalography patterns iops patients drugresistant temporal lobe epilepsy tle examined whether iops relate different tle subtypes mri findings underlying pathologies evaluated prognostic value predicting surgical outcomemethods retrospectively analyzed data patients tle underwent stereoelectroencephalography seeg monitoring followed surgical resection january 2018 january 2020 seeg recordings independently analyzed two epileptologistsresults fortyfive patients included study 61seizures analyzed five iops identified low voltage fast activity lvfa 443 spikeandwave activity 164 low frequency highamplitude periodic spikes lfps 18 burst highamplitude polyspikes 82 rhythmic sharp activity 13 hz 131 thirtytwo patients found single iop 13 patients two iops five iops found occur medial temporal lobe epilepsy mtle four iops occurred lateral temporal lobe epilepsy ltle lfps common iop distinguish mtle ltle x2 7046 p 0011 among mtle patients lfps exclusively seen cases hippocampal sclerosis x2 5058 p 0038 lvfa associated nonspecific histology x2 6077 p 0023 iops found differ according whether mri scans positive negative surgery patients achieved higher seizurefree rate 818 778 respectively lfps lvfa predominant patterns multiple iops negative mri indicate poor prognosisconclusions five distinct iops identified patients tle differences found important clinical implications provide complementary information surgical decisionmaking especially mrinegative patientspmid35041086 doi101007 s0070102205122z,0.0
cost illness multiple sclerosis isfahan iran social perspective comparison humancapital frictioncost methods value health reg issues 2022 jan 15 302630 doi 101016 jvhri202110006 online ahead printabstractobjectives multiple sclerosis ms chronic autoimmune disease central nervous system characterized demyelination neurodegenerative changes associated high levels disability study aimed investigate direct indirect costs illness patients ms isfahan using comparing humancapital frictioncost methods societal perspectivemethods total 300 patients ms 2 main centers disease isfahan ms center ayatollah kashani hospital isfahan ms center included patients demographic characteristics disease information annual social costs 20182019 collected using data collection form humancapital frictioncost methods applied compared value indirect costs loss productivityresults social perspective average annual total cost ms disease estimated 1 441 163 710 rials 34 313 us dollar usd per patient using humancapital approach 1 434 832 004 rials 34 162 usd use frictioncost method 1 428 668 396 rials 34 016 usd related direct costs main direct costs related diseasemodifying therapies referring physicians hospitals cost loss production greater humancapital approach comparison frictioncost methodconclusions prominent cost ms disease related drug costs indirect costs sensitive methods applied studypmid35042020 doi101016 jvhri202110006,1.0
osteochondrosis lesions intervertebral articular process rib joints occiput sacrum pigs poor back conformation relationship juvenile kyphosis background computed tomography ct used evaluate body composition limb osteochondrosis selection breeding boars pigs also develop heritably predisposed abnormal curvature spine including juvenile kyphosis suggested osteochondrosislike changes cause vertebral wedging kyphosis identifiable ct aim current study examine spine occiput sacrum map changes evaluate relationships especially whether osteochondrosis caused juvenile kyphosis case ct used selection wholebody ct scans collected retrospectively 37 landrace duroc boars poor back conformation scores spine curvature vertebral shape evaluated intervertebral articular process rib joints occiput sacrum assessed osteochondrosis lesionsresultstwentyseven 37 73 pigs normal spine curvature whereas 10 37 27 pigs abnormal curvature wedge vertebrae 37 pigs 875 focal lesions articular process rib joints 985 represented stages osteochondrosis five 37 pigs focal lesions parts vertebrae mainly consisting vertebral body osteochondrosis 10 pigs abnormal curvature 21 wedge vertebrae comprising 10 vertebrae without focal lesions six ventral wedge vertebrae ventral osteochondrosis lesions five dorsal wedge vertebrae lesions neurocentral synchondrosis articular process rib jointsconclusionscomputed tomography suited identification wedge vertebrae kyphosis due ventral wedge vertebrae compatible heritably predisposed vertebral body osteochondrosis articular process rib joint osteochondrosis may represent incidental findings wedge vertebrae role neurocentral synchondrosis pathogenesis vertebral wedging warrants investigation,0.0
validity reliability 3meter backward walk test mildly disabled persons multiple sclerosis abstractbackgroundone biggest problems persons multiple sclerosis pwms dizziness poor posture balance problems cause injurycausing falls aim study reveal testretest reliability validity 3meter backward walk test 3mbwt mildly disabled pwmsmethodsthis study included total 93 mildly disabled pwms mean edss 189 3mbwt functional access test frt dynamic gait index dgi timed 25foot walk t25fw timedup go tug applied patients measure testretest reliability second evaluation performed three days first evaluationresultscronbachnulls alpha coefficient found 0998 excellent intrarater agreement icc values individual test 0998 sem value 018 mdc value found 050 strong correlation revealed 3mbwt frt r 0931 p 0001 tug r 0968 p 0001 t25fw r 0879 p 0001 dgi r 0871 p 0001 falling history r 0932 p 0001 conclusionthe 3mbwt observed valid reliable mildly disabled pwms 3mbwt effective reliable tool measuring ability walk backward mildly disabled pwms,0.0
maslinic acid activates renal ampk#x2f sirt1 signaling pathway protects diabetic nephropathy mice background diabetic nephropathy devastating complication clinically urgent need nephroprotective agents delay onset diabetic nephropathy ameliorate symptoms maslinic acid pentacyclic triterpene acid protective effect multiple organs oxidative stress inflammation research hypothesized maslinic acid protects renal function diabetic nephropathymethodsc57bl 6 j male mice administrated 50 mg kg streptozocin stz daily used establish diabetic mouse model blood glucose levels 300 mg dl urinary levels albumin total proteins creatinine analyzed automatic analyzer staining used evaluate renal damage qrtpcr elisa performed investigate inflammation oxidative stress renal tissues western blot used assess activation ampk signalingresultsmaslinic acid treatment alleviated loss body weight blood glucose diabetic mice renal structure function protected maslinic acid diabetic mice 20 mg kg maslinic acid treatment 8 weeks significantly alleviated oxidative stress inflammation kidney diabetic rats maslinic acid treatment activated renal ampk sirt1 signaling pathwayconclusionmaslinic acid ameliorates diabetic nephropathy activates renal ampk sirt1 signaling pathway,0.0
high increasing serum nfl predictive impending multiple sclerosis relapses abstractbackgroundoneoff serum levels neurofilament light chain snfl established predictor emerging disease activity multiple sclerosis ms however importance longitudinal increases snfl yet enumerated important consideration test translated serial monitoring glial fibrillary acidic protein sgfap another biomarker predictive interest objective assess association longitudinal changes snfl prediction future relapses well possible role sgfapmethodsparticipants active ms prospectively monitored one year part clinical trial testing mesenchymal stem cells visits every three months less included clinical assessments mri scans serum draws snfl sgfap concentrations quantified single molecule array immunoassay used kaplanmeier estimates andersongill cox regression models without adjustment age sex disease subtype disease duration expanded disability status score edss estimate rate relapse predicted baseline longitudinal changes biomarkerresults58 canadian italian participants ms enrolled study higher baseline snfl future relapse logrank p00068 mri lesions p00096 compositerelapse associated worsening p001 progression independent relapse activity p00096 conversely baseline sgfap weakly associated mri lesions 0044 crosssectional analyses baseline snfl revealed twofold difference baseline snfl eg 10 20 pg ml associated 23fold increased risk relapse followup 95 confidence interval 165317 longitudinally twofold increase snfl level first measurement associated additional 146 times increased risk relapse 107200 impact longitudinal increases snfl risk relapse pronounced patients lower baseline values snfl 10 pg ml hr154 106224 associations remained significant adjustment potential confoundersconclusionwe enumerate risk relapse associated dynamic changes snfl baseline longitudinal change snfl may help identify patients benefit early treatment optimisationtrial registrationscanadanct02239393 italynct01854957eudract 201100129519classification evidencethis study provides class 1 evidence high baseline longitudinal increases snfl predictive impending relapses patients active ms,0.0
prioritising referrals individuals atrisk ra guidance based results 10year national primary care observational study background musculoskeletal msk symptoms among commonest reasons primary care assessments however individuals will diagnosed inflammatory arthritis ia within following year purpose study investigate individuals new msk symptoms association patient factors risk progression ia order optimise primary care referrals rheumatologymethodsindividuals 16 years old new nonspecific msk symptoms clinical synovitis recruited primary care across uk july 2007 may 2019 testing positive anticcp2 assay anticcp+ invited leeds followup subjects negative result anticcp sent 1year questionnaire general practitioners contacted confirm whether individual diagnosed ia rheumatologist predictors progression assessed using multivariable regression analysisresultssix thousand seven hundred eighty individuals recruited 3 anticcp+ 45 progressed ia predominantly rheumatoid arthritis anticcp+ participants high antibody levels odds ratio progression ia 942 p 0001 95 ci 3132830 hand pain 274 p 0043 95 ci 103727 foot pain 410 p 0003 95 ci 1591054 lowlevel anticcp+ individuals absence pain hands feet negative predictive value 96 progression iaoneyear followup data available 5640 anticcp individuals 53 diagnosed ia 093 pain hands 251 p 0018 95 ci 117539 knees 303 p 0003 95 ci 147625 associated development ia within 12 monthsconclusionsthis largest prospective primary care study individuals risk ia first one prospectively investigate outcome msk symptoms large anticcp cohort high anticcp levels pain hands feet indicated increased likelihood progression ia patients low anticcp level pain hands feet progression unlikely anticcp patients hand knee pain increased risk progression study demonstrates routinely available tests joint symptoms provide useful discrimination may used prioritise referrals rheumatology avoid delayed diagnosistrial registrationnct nct02012764 registered 25 january 2007,0.0
emotional processing intervention emoprint blinded randomized control trial treat facial affect recognition deficits multiple sclerosis abstractobjective facial affect recognition deficits noted persons ms however treatment impairments investigated efficacy emotional processing intervention emoprint 12session behavioral intervention teaching facial affect recognition skills mimicry improve facial affect recognition abilities persons msmethods double blind placebocontrolled randomized clinical trial two time points pretreatment posttreatment included 36 participants clinically definite ms 21 treatment group 15 placebo control group participants completed pretest posttest neuropsychological assessment consisted tasks facial affect recognition primary outcome measure questionnaires assess quality life emotional functioning secondary outcome measures hypothesized improvements facial affect recognition skills observed following treatment also examined changes quality life social functioning changes outcome measures analyzed using mixedmethod analysis varianceresults treatment group showed significantly improved facial affect recognition skills relative placebo group posttreatment f 1 34 591 p022 partial 20146 significant change noted secondary outcomes majority participants intervention group reported intervention helpful used skills learned daily interactionsconclusion emoprint effective improving facial affect recognition skills ms,0.0
editors impact mass vaccination sarscov2 infections among multiple sclerosis patients taking immunomodulatory diseasemodifying therapies england available,0.0
season birth associated multiple sclerosis disease severity mult scler j exp transl clin 2021 dec 22 7 4 20552173211065730 doi 101177 20552173211065730 ecollection 2021 octabstractbackground latitude gradient multiple sclerosis incidence indicates low sun exposure therefore vitamin d deficiency associated multiple sclerosis riskobjective investigation effect month birth influences postnatal vitamin d levels multiple sclerosis risk severity swedenmethods patients populationbased controls included three nationwide cohorts differences month birth cases controls analyzed using logistic regression examined effect modification calendar year geographic region birthresults males reduced risk multiple sclerosis born winter increased risk born early fall individuals born 1960 increased risk born summer fall born late summer early fall associated severe diseaseconclusions identified birth cohort effect association month birth multiple sclerosis significant effects births 1960 coincides period lower breastfeeding rates recommended intake vitamin d sun exposure resulting lower vitamin d exposure fall winter season infants born summerpmid35035988 pmcpmc8753082 doi101177 20552173211065730,0.0
nfl acute spinal cord lesions ms hurdle detection inflammatory activity j neurol 2022 jan 17 doi 101007 s00415021109267 online ahead printabstractintroduction levels neurofilament light chain nfl correlate clinical radiological activity multiple sclerosis ms used surrogate biomarker axonal destruction related inflammatory activity main objective work explore specific contribution acute inflammation within spinal cord elevation nfl levelspatients methods ms patients baseline study nfl diagnosis disease brain spinal cord mri scan selected patients classified according presence number location gadolinium enhancing lesion gel relationship nfl levels brain spinal cord gel exploredresults seventyseven patients selected nfl levels significantly higher patients one gel restricted brain without gel 1702 pg ml vs 7227 pg ml p 003 correlated number however differences seen among patients gel limited spinal cord without gel 7352 pg ml vs 7227 pg ml conclusion study reaffirms value nfl levels monitoring asymptomatic inflammatory activity brain measured gel however nfl concentration useful inflammatory activity occurs spinal cordpmid35038000 doi101007 s00415021109267,0.0
happy anniversary narcoms int j ms care 2021 novdec 23 6 iv doi 107224 15372073236ivb epub 2021 dec 29no abstractpmid35035300 pmcpmc8745230 doi107224 15372073236ivb,0.0
multiple sclerosis data alliance catalogue enabling webbased discovery metadata realworld multiple sclerosis data sources int j ms care 2021 novdec 23 6 261268 doi 107224 153720732021006 epub 2021 dec 29abstractbackground one major objectives multiple sclerosis data alliance msda enable better discovery multiple sclerosis ms realworld data rwd methods implemented msda catalogue available worldwide current version msda catalogue collects descriptive information governance purpose inclusion criteria procedures data quality control data collected including use ehealth technologies data collection covid19 variables current cataloguing procedure performed several manual steps securing effective catalogueresults herein summarize status msda catalogue january 6 2021 date 38 data sources across five continents included msda catalogue data sources differ purpose maturity variables collected landscaping effort shows substantial alignment domains msda catalogue shows personal data basic disease data collected categories variables whereas data fatigue measurements cognition scales least collected ms registries cohortsconclusions webbased msda catalogue provides strategic overview allows authorized end users browse metadata profiles data cohorts data sources many existing arising rwd sources ms detailed cataloguing ms rwd first useful step toward reducing time needed discover ms rwd sets promoting collaborationpmid35035297 pmcpmc8745233 doi107224 153720732021006,0.0
identifying candidate genes associated sporadic amyotrophic lateral sclerosis via integrative analysis transcriptomewide association study messenger rna expression profile cell mol neurobiol 2022 jan 17 doi 101007 s10571021011860 online ahead printabstractamyotrophic lateral sclerosis fatal neurodegeneration disease affecting motor neurons brain spinal cord difficult diagnose treat objective study identify novel candidate genes related als transcriptomewide association study als conducted integrating genomewide association study summary data including 1234 als patients 2850 controls precomputed gene expression weights different tissues alsassociated genes identified twas compared differentially expressed genes detected mrna expression profiles sporadic als functional enrichment annotation analysis identified genes performed r package functional mapping annotation software twas identified 761 significant genes ptwas 005 627 gene ontology terms 8 kyoto encyclopedia genes genomes pathways als c9orf72 three expression quantitative trait loci found significantly rs2453554 ptwas cbrs 468 1010 ptwas cbrs 254 109 rs10967976 ptwas cbrs 785 1010 ptwas cbrs 891 109 ptwas cbrs 149 107 ptwas cbrs 559 107 rs3849946 ptwas cbrs 769 104 ptwas ybl 402 102 mitochondrion padj 422 1016 cell cycle padj 204 103 moreover 107 common genes 4 kegg pathways 41 go terms detected integrating mrna expression profiles sals cpvl fc 206 pmrna 699 106 ptwas cbr 288 102 ptwas cbr 437 102 pyrimidine metabolism padj 243 102 cell activation padj 554 103 multiple candidate genes pathways detected als findings may provide novel clues understanding genetic mechanism alspmid35038056 doi101007 s10571021011860,0.0
guest editorial int j ms care 2021 novdec 23 6 ivaiv doi 107224 15372073236iva epub 2021 dec 29no abstractpmid35035301 pmcpmc8745231 doi107224 15372073236iva,0.0
north american registry care research multiple sclerosis narcrms int j ms care 2021 novdec 23 6 269275 doi 107224 153720732021021 epub 2021 dec 29abstractalthough many regional multiple sclerosis ms databases existed united states canada single clinicianderived registry examined disease group across north american continent distinction important information results database can potentially give perspectives ms derived single regional registry partnership forged pharmaceutical industry consortium multiple sclerosis centers cmsc create registry patients ms canada united states including puerto rico case report forms created collect physicianderived information patientreported outcomes measurement information system promis selected capture patientreported outcomes november 2021 754 1000 patients enrolled completion recruitment expected end 2021 twentyfive centers participating expected total 30 including five centers canada clinical status health economic outcomes magnetic resonance images soon biomarkers relevant understanding relapses progression collected shortterm goal understand better treat ms disease progression longterm goal prevention north american registry care research multiple sclerosis narcrms one clinician patientgenerated registries examines ms across north america including puerto rico information derived natural history studies help physicians pharmaceutical industry regulatory bodies understand ms better improve quality life patients ms worldwidepmid35035298 pmcpmc8745232 doi107224 153720732021021,0.0
narcoms registries multiple sclerosis issues insights int j ms care 2021 novdec 23 6 276284 doi 107224 153720732020133 epub 2021 dec 29abstractobservational studies registries can play critical role elucidating natural treated history multiple sclerosis ms identifying factors associated outcomes disability healthrelated quality life north american research committee multiple sclerosis narcoms registry one multiple registries worldwide focuses people ms one patientdriven ms registries 25th anniversary first data collection narcoms registry discuss importance disease registries ms field describe key concepts related registry design management highlight findings ms registries relevant clinical care health policypmid35035299 pmcpmc8745235 doi107224 153720732020133,0.0
prevalence osteoporosis#x2f osteopenia patients multiple sclerosis ms systematic review metaanalysis neurol sci 2022 jan 17 doi 101007 s1007202205871w online ahead printabstractbackground prevalence osteoporosis reported differently designed systematic review metaanalysis estimate pooled prevalence osteoporosis osteopenia patients msmethods independently two researchers searched pubmed scopus embase web science google scholar along gray literature conference abstracts references references march 2021 collected data regarding first author country origin number enrolled patients number cases osteoporosis osteopenia mean age f m ratio mean edss mean duration diseaseresults literature search revealed 847 articles 658 remained deleting duplicates finally 29 original articles 6 conference papers remained metaanalysis total 13 906 patients evaluated pooled prevalence osteoporosis 17 95 ci 1420 i2 904 p 0001 pooled prevalence osteopenia 43 95 ci 3551 i2 979 p 0001 conclusion osteoporosis osteopenia considered patients mspmid35038045 doi101007 s1007202205871w,0.0
structural functional markers optic nerve damage myelin oligodendrocyte glycoprotein antibodyassociated optic neuritis mult scler j exp transl clin 2021 dec 21 7 4 20552173211063126 doi 101177 20552173211063126 ecollection 2021 octabstractbackground optic neuritis occurs immunemediated disorders including multiple sclerosis ms aquaporin4 antibodypositive aqp4 neuromyelitis optica spectrum disorder aqp4nmosd myelin oligodendrocyte glycoprotein mog antibodyassociated demyelination mogad accurate determination aetiology critical appropriate treatment prognosticationobjective evaluate demyelination axonal loss mogon facilitate differentiation mson aqp4onmethods 15 mogad patients previous 25 eyes underwent multifocal visual evoked potential mfvep recordings optical coherence tomography scans comparison made previously reported ms patients n 67 69 eyes aqp4nmosd patients n 15 23 eyes prior healthy controls n 37 74 eyes results mogon patients less retinal nerve fibre layer rnfl loss aqp4on patients p 005 less mfvep latency prolongation mson patients p 001 number episodes mogad associated reduced rnfl thickness global p 007 temporal p 0001 mfvep amplitude p 0001 abnormality nonon eyesconclusions study demonstrated distinct pattern damage mogon compared aqp4on mson mogad produces less axonal loss aqp4nmosd damage accumulates relapses supporting role maintenance immunosuppression induce remission compared ms mogad causes less demyelinationpmid35035987 pmcpmc8753081 doi101177 20552173211063126,1.0
mick mobile integrated cognitive kit app digital rapid automatized naming visual assessment across spectrum neurological disorders j neurol sci 2022 jan 11 434120150 doi 101016 jjns2022120150 online ahead printabstractobjective rapid automatized naming ran tasks utilized decades evaluate neurological conditions time scores mobile universal lexicon evaluation system mules rapid picture naming staggered uneven number sun rapid number naming prolonged worse concussion mild cognitive impairment multiple sclerosis parkinsons disease purpose investigation compare paper pencil versions mules sun new digitized format mick appmethods participants healthy officebased volunteers professional womens hockey players completed two trials mules sun tests platforms tablet paper pencil order presentation testing platforms randomized betweenplatform variability calculated using twoway randomeffects intraclass correlation coefficient icc results among 59 participants median age 32 range 2283 significant differences observed comparisons mean best scores paper pencil versus mick app platforms counterbalanced order administration p 045 mules p 050 sun linear regression iccs agreement mick paper pencil tests 092 95 ci 086 095 mules 094 95 ci 089 096 sun representing excellent levels agreement interplatform differences vary systematically across range average best time score either testconclusion mick app digital administration mules sun demonstrates excellent agreement time scores paper pencil testing computerized app allows greater accessibility scalability neurological diseases inclusive remote monitoring sideline testing sportsrelated concussion may also benefit technologypmid35038658 doi101016 jjns2022120150,0.0
serum nfl levels first five years predict 10year thalamic fraction patients ms mult scler j exp transl clin 2022 jan 10 8 1 20552173211069348 doi 101177 20552173211069348 ecollection 2022 janmarabstractbackground serum neurofilament light chain snfl levels associated relapses mri lesions brain volume multiple sclerosis ms objective explore value early serum neurofilament light snfl measures prognosticating 10year regional brain volumes msmethods patients ms enrolled comprehensive longitudinal investigations ms brigham womens hospital climb study within five years disease onset annual blood samples years 110 n 91 studied snfl measured single molecule array simoa assay quantified global cortical thickness normalized deep gray matter dgm volumes fractions thalamus caudate putamen globus pallidus highresolution 3 t mri 10 years correlations yearly snfl levels 10year mri outcomes assessed using linear regression modelsresults snfl levels years 1 2 associated 10year thalamus fraction early snfl levels associated 10year putamen globus pallidus caudate fractions 10 years cortical thickness associated early snfl levels weakly correlated total dgm fractionconclusions early snfl levels correlate 10year thalamic volume supporting role prognostic biomarker mspmid35035990 pmcpmc8753083 doi101177 20552173211069348,0.0
lifestyle complementary therapies multiple sclerosis guidelines systematic review acta neurol scand 2022 jan 17 doi 101111 ane13574 online ahead printabstractmanagement multiple sclerosis ms may comprise clinical interventions selfmanagement strategies including complementary therapies modifiable lifestyle factors exercise smoking cessation lifestyle modifications complementary therapies proven safety efficacy essential part bestpractice ms management especially faced limited access healthcare services however unclear extent ms clinical practice guidelines consensus statements address strategies systematic review conducted wherein medline embase psycinfo cinahl scopus web science guideline databases developer sites searched guidelines consensus statements addressed lifestyle modifications complementary therapies interest two researchers independently screened articles extracted data assessed guideline quality using appraisal guidelines research evaluation version ii thirtyone guidelines consensus statements included quality high clarity presentation 77 scope purpose 73 moderate stakeholder development 56 rigour development 48 editorial independence 47 low applicability 29 two guidelines related physical activity exercise mindfulness smoking cessation vitamin d polyunsaturated fatty acid supplementation scored high domains guidelines two four guidelines intended use people ms highquality guidelines consensus statements guide lifestyle modifications complementary therapies ms management limited findings indicate need guidelines intended use people ms focus implementation resourcespmid35037722 doi101111 ane13574,0.0
pelvic floor muscle training urinary incontinence sexual function people multiple sclerosis systematic review abstractobjectivethis systematic review evaluates summarizes effects pelvic floor muscle training urinary incontinence sexual function people multiple sclerosisdata sourcespubmed scopus pedro cinahl web science ulakbim databases keywords multiple sclerosis urinary incontinence sexual function pelvic floor muscle training screened randomized controlled studies clinical trials beginning july 2020 updated august 2021 review methodstwo authors independently made study selection turkish english publications taken consideration risk bias included studies assessed using revised cochrane riskofbias tool randomized trials tool assessment study quality reporting exercise testext used assess methodological quality studies data extraction performed two researchers independentlyresultsinitial search identified total 2831 studies removing duplicates 2180 records screened 7 studies 248 participants mean age years 5001111 range 2067 mean expanded disability status scale score 42164 range 1575 met inclusion criteria one study included male people multiple sclerosis five studies judged concerns two studies judged high risk bias testext scores ranged 5 9 15 outcome measures healthrelated quality life 6 studies severity overactive bladder 5 studies leakage episodes 4 studies severity urinary incontinence 3 studies 24hour pad test 2 studies pad usage sexual function anxiety depression 1 study significant improvements observed specified outcome measures groups received pelvic floor muscle training majority studiesconclusioncurrent evidence suggests pelvic floor muscle training seems effective treatment modality improving healthrelated quality life reducing severity urinary incontinence overactive bladder symptoms people multiple sclerosis also can reduce leakage episodes pad usage anxiety depression improve sexual function however noted included studies concerns high risk bias least one domain risk bias assessment studies high quality,0.0
short structural variants informative genetic markers als disease risk progression abstractthere considerable variability disease progression patients amyotrophic lateral sclerosis als including age disease onset site disease onset survival time growing evidence short structural variations ssvs residing frequently overlooked genomic regions can contribute complex disease mechanisms can explain part phenotypic variability als patients discuss ssvs recently characterized laboratory discoveries integrate current literature als particularly context application future clinical trials markers may help identify differentiate patients clinical trials similar als disease mechanism s thereby reducing impact participant heterogeneity evidence accumulates genetic markers discovered sqstm1 scaf4 stmn2 hope improve outcomes future als clinical trials,0.0
cns malformations newborn abstractstructural brain anomalies relatively common may detected either prenatally postnatally brain malformations can characterized based developmental processes perturbed either environmental infectious disruptive genetic causes fetuses neonates brain malformations thoroughly surveilled potential anomalies depending nature brain malformation may require additional investigations genetic testing ophthalmological examinations cardiorespiratory monitoring screening laboratory studies,0.0
special role cxcl13 lyme neuroborreliosis case report abstractthe diagnosis chronic lyme neuroborreliosis can challenge even experienced neurologists clinical picture may multifaceted including polyradiculitis cranial nerve palsies meningitis encephalomyelitis encephalopathy peripheral neuropathy report patient presenting basal leptomeningoencephalitis associated vasculopathy chemokine cxcl13 cerebrospinal fluid played important diagnostic role,0.0
it#39 s time talk disclosure concealment ms summarydeciding disclose diagnosis multiple sclerosis ms complicated highly stressful individuals already facing many challenges date research studies explored specific ways challenge affects people ms cognitive neuroscience standpoint brain limited capacity system whereby allocation resources consequence overall brain efficiency better understand consequences allocating resources concealment behaviors disclosure decisions developed measurement tool discoms discuss insights gained followup focus group discussions ms patients,0.0
remyelination trial failures repercussions ignoring neurorehabilitation exercise repair abstractseveral putative neurorestorative therapies multiple sclerosis ms recently failed includes highdose biotin bexarotene retinoic acid receptor gamma agonist opicinumab antilingo1 failures biological due poor trial design argue failure include exercise trials selecting participants without capacity repair may explain disappointing results propose need mapping biological mechanisms recovery within trials understanding critical window remyelination repair occurs terms targeting interventions right time selecting subjects capable repair also make case testing combinations include prorepair interventions exercise nrf2 inducers possibly neurostimulation ms community cannullt afford treatments fail poor trial design ignoring biology,1.0
diagnosis concealment associated psychosocial outcomes persons multiple sclerosis abstractpersons multiple sclerosis pwms frequently conceal diagnosis fearing professional personal repercussions disclosing associations concealment behavior expected consequences disclosure psychosocial outcomes examined 90 pwms completed validated selfreport measures diagnosis concealment loneliness social support selfefficacy frequent concealment related worse loneliness rp 0213 p 0045 lower social support rp 0211 p 0047 controlling depression higher anticipated negative consequences disclosure associated worse loneliness rp 0263 p 0013 lower social support rp 0338 p 0001 lower selfefficacy rp 0350 p 0001 findings hold implications development psychological support strategies addressing concealment disclosure issues psychosocial consequences,0.0
peripheral magnetic theta burst stimulation muscles can effectively reduce spasticity randomized controlled trial background spasticity common complication many neurological diseases despite contributing much disability available therapeutic options limited peripheral magnetic stimulation one promising option study investigated whether peripheral intermittent theta burst stimulation pitbs will reduce spasticity applied directly spastic musclesmethodsin shamcontrolled study eight successive sessions pitbs applied directly spastic muscles supra threshold intensity assessment done modified ashworth scale mas estimated botulinum toxin dose ebtd baseline 8th session active sham groupsresultsa total 120 spastic muscles 36 patients included analysis significant reduction mas ebtd found active compared sham group p 0001 difference mas also significant tested upper limb lower limb subgroups degree reduction mas positively correlated baseline scores active groupconclusionpitbs promising method reduce spasticity ebtd consumes less time standard high frequency protocols without compromising treatment efficacytrial registration clinical trial registry number pactr202009622405087 retrospectively registered 14th september 2020,0.0
identification ferroptosisrelated gene pair biomarker immune infiltration landscapes ischemic stroke bioinformaticsbased comprehensive study background ischemic stroke principal contributor longterm disability adults new cell death mediated iron ferroptosis characterized lethal aggregation lipid peroxidation however paucity ferroptosisrelated biomarkers early identify now study investigated potential ferroptosisrelated gene pair biomarkers explored roles immune infiltrationresultsin total identified 6 differentially expressed ferroptosisrelated genes defrgs metadata cohort genes 4 defrgs incorporated competitive endogenous rna cerna network including 78 lncrnamirna 16 mirnamrna interactions based relative expression values defrgs constructed gene pairs integrated scheme consisting machine learning algorithms cerna network gene pair proposed screen key defrg biomarkers receiver operating characteristic roc curve witnessed diagnostic performance defrg pair cdkn1a jun superior single gene moreover cibersort algorithm exhibited immune infiltration landscapes plasma cells resting nk cells resting mast cells infiltrated less samples controls spearman correlation analysis confirmed significant correlation plasma cells cdkn1a jun cdkn1a r 0503 p 0001 jun r 0330 p 0025 conclusionsour findings suggested cdkn1a jun robust promising genepair diagnostic biomarker regulating ferroptosis progression via c9orf106 c9orf139mir223pcdkn1a gas5mir1395p mir429jun axes meanwhile plasma cells might exert vital interplay immune microenvironment providing innovative insight therapeutic target,0.0
a20 tnfaip3 alleviates viral myocarditis adar1#x2f mir1a3pdependent regulation abstractobjectiveto investigate effect a20 a20 regulated viral myocarditis vmc methodsbabl c mice primary neonatal rat cardiomyocytes h9c2 cells infected coxsackie virus b3 cvb3 establish animal cellular models vmc staining revealed pathologic condition myocardium elisa measured serum levels creatine kinase creatine kinase isoenzyme cardiac troponin effects a20 mir1a3p adar1 investigated using gain loss function approaches elisa measured levels il6 il18 tnf serum cell culture supernatant tunel staining flow cytometry assessed apoptosis myocardium cardiomyocytes respectively rnabinding protein immunoprecipitation dualluciferase reporter assays verified binding a20 mir1a3p coimmunoprecipitation assay verified binding adar1 dicerresultsa20 underexpressed mir1a3p overexpressed myocardium vmc mice well cvb3infected cardiomyocytes overexpression a20 suppressed cardiomyocyte inflammation apoptosis vivo vitro mir1a3p promoted cvb3induced inflammation apoptosis cardiomyocytes binding a20 expression mir1a3p regulated adar1 adar1 promoted slicing mir1a3p precursor binding dicerconclusiona20 regulated adar1 mir1a3p suppresses inflammation cardiomyocyte apoptosis vmc,0.0
decoding role macrophages periodontitis type 2 diabetes using singlecell rnasequencing abstractmacrophages resident myeloid cells gingival tissue control homeostasis play pivotal role orchestrating immune response periodontitis cell heterogeneity functional phenotypes macrophage subpopulations periodontitis remain elusive isolated gingival tissue periodontitisaffected healthy sites patients without type 2 diabetes mellitus t2dm used singlecell rnasequencing scrnaseq define heterogeneity tissueresident macrophages gingival tissue health vs periodontitis scrnaseq demonstrated unforeseen gene expression heterogeneity among macrophages periodontitis showed transcriptional signaling heterogeneity identified subsets independent cohort patients periodontitis t2dm bioinformatic inferences indicated divergent expression profiles macrophages driven transcriptional regulators ciita rela rfx5 runx2 macrophages periodontitis expressed proinflammatory antiinflammatory markers polarization mutually exclusive majority macrophages periodontitis expressed monocyte lineage marker cd14 indicating bone marrow lineage also found high expression activation rela subunit nfb transcription factor complex gingival macrophages periodontitis patients t2dm data suggested heterogeneity hyperinflammatory activation macrophages may relevant pathogenesis outcomes periodontitis may augmented patients t2dm,0.0
first evidence longterm effects transcranial pulse stimulation tps human brain background high spatial resolution potential reach deep brain structures ultrasoundbased brain stimulation techniques offer new opportunities noninvasively treat neurological psychiatric disorders however little known longterm effects ultrasoundbased brain stimulation applying longitudinal design comprehensively investigated neuromodulation induced ultrasound brain stimulation provide first shamcontrolled evidence longterm effects human brain behaviormethodstwelve healthy participants received three sham three verum sessions transcranial pulse stimulation tps focused cortical somatosensory representation right hand one week sham verum tps applications comprehensive structural functional resting state mri investigations behavioral tests targeting tactile spatial discrimination sensorimotor dexterity performedresultscompared sham global efficiency significantly increased within cortical sensorimotor network verum tps indicating upregulation stimulated functional brain network axial diffusivity left sensorimotor areas decreased verum tps demonstrating improved axonal status stimulated areaconclusionstps increased functional structural coupling within stimulated left primary somatosensory cortex adjacent sensorimotor areas one week last stimulation findings suggest tps induces neuroplastic changes go beyond spatial temporal stimulation settings encouraging clinical applications,0.0
engineered adiposederived stem cells igf1modified mrna ameliorates osteoarthritis development background osteoarthritis oa prevalent degenerative disease characterized degradation extracellular matrix ecm still lacks effective diseasemodifying therapy mesenchymal stem cells mscs transplantation regarded promising approach oa treatment engrafting cells alone might adequate effective regeneration genetic modification used optimize mscbased therapy however still significant limitations prevent clinical translation therapy including low efficacy safety concerns recently chemically modified mrna modrna represents promising alternative geneenhanced msc therapy regard hypothesized adipose derived stem cells adscs engineered modrna encoding insulinlike growth factor 1 igf1 superior native adscs ameliorating oa developmentmethodsmouse adscs acquired adipose tissue transfected modrnas first kinetics efficacy modrnamediated gene transfer mouse adscs analyzed vitro next applied indirect coculture system analyze proanabolic potential igf1 modrna engineered adscs named igf1adscs chondrocytes finally evaluated cell retention chondroprotective effect igf1adscs vivo using fluorescent labeling histology immunohistochemistryresultsmodrna transfected mouse adscs high efficiency 85 5 igf1 modrnatransfected adscs facilitated burstlike production biofunctional igf1 protein vitro igf1adscs induced increased anabolic markers expression chondrocytes inflammation environment compared untreated adscs murine oa model histological immunohistochemical analysis knee joints harvested 4 weeks 8 weeks oa induction suggested igf1adscs superior therapeutic effect native adscs demonstrated lower histological oarsi score decreased loss cartilage ecmconclusionsthese findings collectively supported therapeutic potential igf1adscs clinical oa management cartilage repair,0.0
consistency central vein sign chronic multiple sclerosis lesions abstractbackgroundin recent years increasing interest central vein sign cvs new imaging marker previous crosssectional studies demonstrated cvs potential discriminate multiple sclerosis ms lesions nonms lesions aim study investigate consistency cvs longitudinal magnetic resonance imaging mri data setmethods3t mri datasets seventyone people ms acquired baseline 12 monthsfollowup analyzed chronic lesions identified fluidattenuated inversion recovery flair images coregistered susceptibilityweighted flair images analyzed presence cvs baseline followupresultsa total 183 chronic lesions included final analysis baseline mri cvs detectable 141 183 77 lesions overall cvs consistent 114 141 81 lesions cohennulls kappa046 standard error007 conclusionthe cvs rather stable feature chronic ms lesions therefore represents robust imaging marker increase specificity mri ms,0.0
cognitive rehabilitation outcomes patients multiple sclerosis preliminary data potential role personality traits abstractbackground multiple sclerosis ms can associated personality changes personality traits affect cognitive functions mood psychological wellbeing people ms families objective aim study evaluate whether personality traits might predictors cognitive recovery people ms methods thirtyone patients diagnosis ms enrolled study participant evaluated neuropsychologist t0 end rehabilitation treatment t1 fivefactor model ffm used describe basic personality structure highlighting five personality traits extroversion neuroticism conscientiousness agreeableness openness rehabilitation program included conventional physiotherapy speech therapy psychological support cognitive rehabilitation nutritional therapy well robotic rehabilitation advanced cognitive rehabilitation virtual reality logistic regressions carried measure changes score t0 t1 results results showed patients significant improvement cognitive behavioral functioning considered relationships scores cognitive emotional behavioral domains five scales bfq besides psychiatric symptoms particular mental quality life visuospatial verbal longterm memory positively influenced agreeableness trait depression negatively affected trait conclusion data suggest personality traits influence cognitive behavioral recovery patients ms,0.0
downregulation brainspecific celladhesion molecule contactin3 tuberous sclerosis complex early postnatal period background genetic disorder tuberous sclerosis complex tsc frequently accompanied development neuropsychiatric disorders including autism spectrum disorder intellectual disability varying degrees impairment comorbidities tsc linked structural brain abnormalities cortical tubers recurrent epileptic seizures 7080 cases previous transcriptomic analysis cortical tubers revealed dysregulation genes involved cell adhesion brain may associated neurodevelopmental deficits tsc study aimed investigate expression one genes celladhesion molecule contactin3methodsreverse transcription quantitative polymerase chain reaction contactin3 gene cntn3 performed resected cortical tubers tsc patients drugresistant epilepsy n 35 age range 148 years compared autopsyderived cortical control tissue n 27 age range 044 years well western blot analysis contactin3 n 7 vs n 7 age range 03 years tsc controls immunohistochemistry n 5 tsc vs n 4 controls expression contactin3 analyzed fetal postnatal control tissue western blotting insitu hybridization well shsy5y neuroblastoma cell line differentiation model vitroresults cntn3 gene expression lower cortical tubers patients across wide range ages fold change 05 p 0001 compared controls contactin3 protein expression lower age range 03 years old fold change 38 p 0001 compared agematched controls control brain tissue contactin3 gene protein expression detected fetal development peaked around birth infancy declined adult brain cntn3 expression induced differentiated shsy5y neuroblastoma cells vitro fold change 62 p 001 conclusionsour data show lower expression contactin3 cortical tubers tsc patients early postnatal period compared controls may affect normal brain development might contribute neuropsychiatric comorbidities observed patients tsc,0.0
individualized strategy minimally invasive cardiac surgery congenital cardiac septal defects background intracardiac septal defect repaired using median sternotomy centers however several reports using minimally invasive surgery children adults study summarized strategy minimally invasive therapy using various lateral minithoracotomies patients congenital septal defectmethodsin study 472 patients underwent minimally invasive repair intracardiac septal defects atrial septal defect asd ventricular septal defect vsd atrioventricular septal defect avsd january 2012 june 2020 retrospectively reviewed underwent device closure excluded minimally invasive strategy included three groups right subaxillary vertical incision rsavi group n 335 including192 asds 135 vsds 8 avsds right anterolateral thoracotomy ralt group n 132 including 77 asds 51 vsds 4 avsds left anterolateral thoracotomy lalt group n 5 subpulmonary vsds resultsconcomitant surgeries included nine cases right ventricular outflow tract obstruction relief nine cases mitral repairs 37 cases tricuspid repairs one transition thoracotomy sternotomy three patients required second pump run residual lesions two residual vsd shunts one mitral regurgitation age body weight rsavi group significantly lower ralt lalt groups p 001 postoperative death observed postoperative complications included one case chest exploration bleeding one case reoperation due patch dehiscence admission one case transient neural dysfunction three cases diaphragmatic paresis 13 cases atelectasis median stay intensive care unit two days median postoperative hospitalization duration six days echocardiography results discharge indicated significant residual lesions reoperation new onset chest deformities sclerosis observed followupconclusionsintracardiac septal defects can safely effectively repaired minimally invasive surgery good cosmetic results rsavi suitable infants children ralt commonly used adolescents adults lalt alternative incision repair subpulmonary vsd,0.0
proteomics based markers clinical pain severity juvenile idiopathic arthritis abstractintroductionjuvenile idiopathic arthritis jia cluster autoimmune rheumatic diseases occurring children 16 years age less wellknown pain may experienced inflammatory noninflammatory states much remains ambiguous regarding molecular mechanisms may drive jia pain thus pilot study explored variability serum proteomes relation pain severity cohort jia patientsmethodsserum samples 15 jia patients male female 127 28 years age assessed using liquid chromatography mass spectrometry lc ms correlation analyses performed determine relationships among protein levels selfreported clinical pain severity additionally expression painassociated proteins related markers inflammation erythrocyte sedimentation rate esr morphological properties central nervous system subcortical volume cortical thickness implicated jia also evaluatedresults306 proteins identified jia cohort 14 significantly p 005 associated clinical pain severity functional properties identified painassociated proteins included limited humoral immunity iglv39 inflammatory response prg4 angiogenesis ang associations among painassociated proteins esr ighv39 prg4 cst3 vwf alb well caudate nucleus volume btd agt ighv374 insular cortex thickness btd lgals3bp also observedconclusionsthe current proteomic findings suggest inflammatory noninflammatory mediated mechanisms potential factors associated jia pain validation preliminary observations using larger patient cohorts longitudinal study design may point novel serologic markers pain jia,0.0
murine roseolovirus accelerate amyloid pathology human roseoloviruses overrepresented alzheimer disease brains background role viral infection alzheimer disease ad pathogenesis area great interest recent years several studies suggested association human roseoloviruses hhv6 hhv7 ad amyloid plaques hallmark neuropathological finding ad recently proposed antimicrobial function response infection identifying causative mechanistic role human roseoloviruses ad confounded limitations performing vivo studies recent omics based approaches demonstrated conflicting associations human roseoloviruses ad murine roseolovirus mrv natural murine pathogen highlyrelated human roseoloviruses providing opportunity perform wellcontrolled studies impact roseolovirus depositionmethodswe utilized 5xfad mouse model test whether mrv induces deposition vivo also evaluated viral load neuropathogenesis mrv infection evaluate interaction mrv performed electron microscopy rnasequencing cohort ad brains compared control used investigate association human roseolovirus adresultswe found 5xfad mice susceptible mrv infection developed neuroinflammation moreover demonstrated interacts viral particles vitro subsequent interaction can disrupt infection despite neither peripheral brain infection mrv increased accelerated plaque formation moreover omics based approaches demonstrated conflicting associations human roseoloviruses ad rnasequencing analysis cohort ad brains compared controls show association roseolovirus infection adconclusionalthough mrv infect brain cause transient neuroinflammation data support role murine human roseoloviruses development plaque formation ad,0.0
simple effective serum biomarkers potential predicting status epilepticus antinmethyldaspartate receptor encephalitis background patients antinmethyldaspartate receptor nmdar encephalitis also present status epilepticus se often poor prognosis aim study explore simple effective predictors antinmdar encephalitis accompanied semethodswe retrospectively analyzed 65 antinmdar encephalitis patients january 2015 december 2018 admitted third affiliated hospital sun yatsen university patients divided se group nonse groups pretreatment data 3month followup data retrospectively analyzedresultsthe results showed compared nonse group levels serum uric acid ua highdensity lipoprotein cholesterol hdlc antinmdar encephalitis patients se decreased significantly treatment additionally levels serum ua hdlc increased level creactive protein crp decreased 3 months treatment se group compared nonse group se patients higher modified rankin scale mrs scores mrs1 treatment mrs2 serum ua concentrations treatment showed significantly negative correlations mrs1 r 0407 p 001 mrs2 r 0458 p 0001 level serum crp treatment strong positive correlations mrs1 r 0304 p 005 mrs2 r 0301 p 005 antinmdar encephalitis patients receiver operating characteristic curve demonstrated combined detection ua hdlc crp treatment significantly higher value area curve 0848 95 confidence interval ci 0740957 p 0001 predict antinmdar encephalitis accompanied se single detectionconclusionshence combined detection serum ua hdlc crp treatment may simple effective indicators predicting se antinmdar encephalitis may helpful early stages remind clinicians alert emergence se,0.0
longterm vivo application potassium channelbased optogenetic silencer healthy epileptic mouse hippocampus background optogenetic tools allow precise manipulation neuronal activity via genetically encoded lightsensitive proteins currently available optogenetic inhibitors suitable prolonged use due shortlasting photocurrents tissue heating unintended changes ion distributions may interfere normal neuron physiology overcome limitations novel potassium channelbased optogenetic silencer named pack recently developed pack tool two components photoactivated adenylyl cyclase beggiatoa bpac campdependent potassium channel sthk carries large longlasting potassium current mammalian cells previously shown activating pack silencer short light pulses led significant reduction neuronal firing various vitro acute vivo settings examined viability performing longterm studies vivo looking inhibitory action side effects pack components healthy epileptic adult male miceresultswe targeted hippocampal cornu ammonis ca1 pyramidal cells using viral vector enabled illumination neurons via implanted optic fiber local field potential lfp recordings ca1 freely moving mice revealed significantly reduced neuronal activity 50min intermittent 01 hz illumination especially gamma frequency range adversely pack expression healthy mice induced chronic astrogliosis dispersion pyramidal cells generalized seizures side effects independent light application also present mice expressing bpac without potassium channel light activation bpac alone increased neuronal activity presumably via enhanced camp signaling furthermore applied bpac pack contralateral hippocampus chronically epileptic mice following unilateral injection intrahippocampal kainate unexpectedly expression bpac contralateral ca1 area sufficient prevent spread spontaneous epileptiform activity seizure focus contralateral hippocampusconclusionour study highlights pack tool potent optogenetic inhibitor vivo however refinement lightsensitive domain required avoid unexpected physiological changes,0.0
frequencies peripheral blood cd5+cd19+ b cells cd3cd16+cd56+ nk cd3+cd56+ nkt cells serum interleukin10 patients multiple sclerosis neuromyelitis optica spectrum disorder background multiple sclerosis ms neuromyelitis optica syndrome disease nmosd inflammatory diseases central nervous system pathogenesis treatments two conditions different natural killer nk natural killer t nkt cells immune cells important role shaping immune response b cells involved antigen presentation well antibody cytokine production conflicting evidence roles nk nkt b cells two conditions aimed compare frequency cd3cd16+cd56+nk cd3+ cd56+ nkt cd5+cd19+ b cells peripheral blood serum interleukin10 il10 patients ms nmosdmethodscd19+cd5+ b cd3 cd16+cd56+ nk cd3+cd56+ nkt cells quantitated flow cytometry 15 individuals interferonbeta ifn treated relapsingremitting ms rrms 15 untreated rrms 15 nmosd patients well 30 healthy controls hc serum il10 measured using enzymelinked immunosorbent assay elisa resultsthe percentage cd3cd56+cd16+ nk cells peripheral blood ifntreated ms 181 087 significantly lower untreated rrms 474 180 nmosd 464 126 hc 583 219 p 00001 also differences percentage cd3cd16+ cd3cd56+ cells p 0001 p 00007 respectively ifntreated rrms 289 151 lowest proportion cd3+cd56+ among study groups p 0002 untreated rrms 556 304 nmosd 547 124 higher levels cd3+cd56+ hc 316 198 mean percentage cd19+cd5+ b cells peripheral blood untreated rrms patients 132 067 higher compared patients nmosd 030 020 hc 05 022 ifntreated rrms 081 017 p 00001 serum interleukin10 significantly higher ifntreated rrms 806 539 hc 838 284 compared untreated rrms 507 144 patients nmosd 533 256 p 0003 conclusionsthe lower proportion cd3cd56+ cd16+ nk cd3+cd56+ cells peripheral blood ifntreated rrms compared groups suggests importance immunomodulation patients rrms disorder based differences cd19+cd5+ b cells serum il10 patients hc supplementary assessments value clarifying roles autoimmunity,0.0
analysis coisogenic prion protein deficient mice reveals behavioral deficits learning impairment enhanced hippocampal excitability background cellular prion protein prpc cell surface gpianchored protein usually known role pathogenesis human animal prionopathies however increasing knowledge participation prpc prion pathogenesis contrasts puzzling data regarding natural physiological role prpc expressed number tissues including high levels nervous system especially neurons glial cells previous studies established neuroprotective role conflicting evidence synaptic function revealed reduced enhanced longterm potentiation variable observations memory learning behavior evidence confounded absence appropriate knockout mouse model dissect biological relevance prpc functions recently shown misattributed prpc due presence genetic artifacts mouse models elucidate role prpc hippocampal circuitry related functions learning memory using recently available strictly coisogenic prnp0 0 mouse model prnpzh3 zh3 resultswe performed behavioral operant conditioning tests evaluate memory learning capabilities results showing decreased motility impaired operant conditioning learning anxietyrelated behavior prnpzh3 zh3 animals also carried vivo electrophysiological recordings ca3ca1 synapses living behaving mice monitored spontaneous neuronal firing network formation primary neuronal cultures prnpzh3 zh3 vs wildtype mice prpc absence enhanced susceptibility highintensity stimulations kainateinduced seizures however longterm potentiation ltp enhanced prnpzh3 zh3 hippocampus addition observed delay neuronal maturation network formation prnpzh3 zh3 culturesconclusionour results demonstrate prpc promotes neuronal network formation connectivity prpc mediates synaptic function protects synapse excitotoxic insults deletion may underlie epileptogenicsusceptible brain fails perform highly cognitivedemanding tasks associative learning anxietylike behaviors,1.0
potential therapeutic options covid19 update current evidence abstractsarscov2 novel coronavirus agent responsible covid19 pandemic major public health concern nowadays rapid global spread coronavirus leads increase hospitalizations thousands deaths many countries date great efforts made worldwide efficient management crisis still effective specific treatment covid19 primary therapies treat disease antivirals antiinflammatories respiratory therapy addition antibody therapies currently many active essential part sarscov2 infection treatment ongoing trials proposed different therapeutic options including various drugs convalescent plasma therapy monoclonal antibodies immunoglobulin therapy cell therapy present study summarized current evidence therapeutic approaches assess efficacy safety covid19 treatment tried provide comprehensive information available potential therapeutic approaches covid19 support researchers physicians current future progress treating covid19 patients,0.0
development validation risk nomogram postoperative acute kidney injury older patients undergoing liver resection pilot study background postoperative acute kidney injury aki associated poor clinical outcomes early identification highrisk patients developing postoperative aki can optimize perioperative renal management facilitate patient survival present study aims develop validate nomogram predict postoperative aki liver resection older patientsmethodsa retrospective observational study conducted involving data 843 older patients scheduled liver resection single tertiary high caseload general hospital 2012 2019 data randomly divided training 70 n 599 validation 30 n 244 datasets training cohort used construct predictive nomogram postoperative aki logistic regression model confirmed validation cohort model evaluated receiver operating characteristic roc curve calibration plot decision curve analysis validation cohort summary risk score also constructed identifying postoperative aki patientsresultspostoperative aki occurred 155 184 patients highly associated inhospital mortality 52 vs 07 p 0001 six predictors selected assembled nomogram included age preexisting chronic kidney disease ckd nonsteroidal antiinflammatory drugs nsaids usage intraoperative hepatic inflow occlusion blood loss transfusion predictive nomogram performed well terms discrimination area roc curve auc training 073 95 confidence interval ci 068078 validation 071 95 ci 063080 datasets nomogram wellcalibrated hosmerlemeshow chisquare value 968 p 047 decision curve analysis demonstrated significant clinical benefit summary risk score calculated sum points six variables one point variable performed well nomogram identifying risk aki auc 071 95 ci 066076 conclusionthis nomogram summary risk score accurately predicted postoperative aki using six clinically accessible variables potential application facilitating optimized perioperative renal management older patients undergoing liver resectiontrial registrationnct04922866 retrospectively registered clinicaltrialsgov june 11 2021,0.0
short inertial sensorbased gait tests reflect perceived state fatigue multiple sclerosis abstractbackground multiple sclerosis ms chronic autoimmune inflammatory disease central nervous system affecting 23 million people worldwide fatigue among common symptoms ms resulting reduced mobility quality life sixminute walking test 6mwt commonly used measure fatigability assessment state fatigue throughout treatment rehabilitation programs gold standardnull test timeconsuming can difficult exhausting patients high levels disability high rates fatigueresearch question can short inertial sensorbased gait tests assess perceived state fatigue ms patientsmethods sixtyfive ms patients equipped one sensor foot performed 6minute walk test 6mwt 25foot walk 25fw preferred fastest speed perceived state fatigue measured minute 6mwt using borg rating highest ratings served measure overall perceived state fatigue stridewise spatiotemporal gait parameters extracted 25fw first minute first 2 minutes first 4 minutes 6mwt principal component analysis performed perceived state fatigue predicted regression analysis using principal components gait parameters predictors statistical tests evaluated differences performance full 6mwt shortened 6mwt 25fwresults mean absolute error less 2 points borg rating obtained using shortened 6mwt 25fw significant differences prediction accuracy full 6mwt shortened gait testssignificance possible use shortened gait tests evaluating perceived state fatigue ms patients using inertial sensors substituting long gait tests may reduce burden testing patients clinicians approach taken may prompt future work explore use short bouts realworld walking unobtrusive inertial sensors state fatigue assessment,0.0
plasma lipocalin 2 alzheimers disease potential utility differential diagnosis relationship biomarkers background lipocalin2 glycoprotein involved various physiological pathophysiological processes brain expressed response vascular brain injury well alzheimers disease reactive microglia astrocytes plasma lipocalin2 proposed biomarker alzheimers disease available data scarce inconsistent thus evaluated plasma lipocalin2 context alzheimers disease differential diagnoses biomarkers clinical datamethodsfor twocenter casecontrol study analyzed lipocalin2 concentrations plasma samples cohort n 407 individuals diagnostic groups comprised alzheimers disease n 74 vascular dementia n 28 important differential diagnoses n 221 healthy controls n 84 main results validated independent cohort patients alzheimers disease n 19 mild cognitive impairment n 27 healthy individuals n 28 resultsplasma lipocalin2 significantly lower alzheimers disease compared healthy controls p 0001 groups p 001 except mixed dementia vascular alzheimers pathologic changes areas curve receiver operation characteristics discrimination alzheimers disease healthy controls 0783 95ci 07120855 study cohort 0766 95ci 06270905 validation cohort area curve alzheimers disease versus vascular dementia 0778 95ci 06670890 study cohort alzheimers disease patients plasma lipocalin2 show significant correlation cerebrospinal fluid biomarkers neurodegeneration adrelated pathology totaltau phosphorylated tau protein betaamyloid 142 cognitive status mini mental status examination scores apoe genotype presence white matter hyperintensities interestingly lipocalin 2 lower patients rapid disease course compared patients nonrapidly progressive alzheimers disease p 0013 conclusionsplasma lipocalin2 potential diagnostic biomarker alzheimers disease seems independent currently employed biomarkers,0.0
characterization use ecv304 autoantigenic citrullinome understand anticitrullinated protein#x2f peptide autoantibodies rheumatoid arthritis background anticitrullinated protein antibodies acpas highly specific rheumatoid arthritis ra vivo acpas target peptidylcitrulline epitopes cit variety proteins citprotacpas derived peptides citpeptacpas generated via peptidylarginine deiminase pad isoenzymes aimed identify cell line selfcitrullination capacity describe autoantigenic citrullinome test source autocitrullinated proteins peptidesmethodshuman cell lines screened citproteins western blot pad isoenzymes identified rtpcr autocitrullination ecv304 optimized ecv304 autocitrullinomes immunoprecipitated sera three ra patients characterized mass spectrometry citpeptacpas detected using anticcp2 elisa citprotacpas autocitprotecv304 elisa sera 177 ra patients 59 nonra rheumatic disease patients 25 nondisease controls testedresultsof seven cell lines studied ecv304 simultaneously overexpressed pad2 pad3 extracts reproducibly autocitrullinated self nonselfproteins proteomic analysis citecv304 products immunoprecipitated ra sera identified novel cittargets calreticulin profilin 1 vinculin new 1433 protein family members chaperones mitochondrial enzymes autocitprotecv304 elisa sensitivity 50 specificity 95 ra diagnosisconclusionsecv304 cells overexpress two pad isoenzymes capable citrullinating selfproteins autocitrullinated cells constitute basic clinical research tool enable detection citprotacpas high diagnostic specificity allow identification specific citproteins targeted individual ra sera,0.0
conventional laboratory housing increases morbidity mortality research rodents results metaanalysis background 120 million mice rats used annually research conventionally housed shoeboxsized cages restrict natural behaviours eg nesting burrowing can reduce physical fitness impair thermoregulation reduce welfare eg inducing abnormal stereotypic behaviours humans chronic stress biological costs increasing disease risks potentially shortening life using preregistered protocol https atriumlibuoguelphca xmlui handle 10214 17955 metaanalysis therefore tested hypothesis compared rodents enriched housing better meets needs conventional housing increases stressrelated morbidity allcause mortalityresultscomprehensive searches via ovid cabi web science proquest scopus may 24 2020 yielded 10 094 publications screening inclusion criteria published english using mice rats providing enrichments longterm housing yielded 214 studies within 165 articles using 6495 animals 591 mice 682 male 318 isolationhoused data allcause mortality plus five experimentally induced stresssensitive diseases anxiety cancer cardiovascular disease depression stroke systematic review center laboratory animal experimentation syrcle tool assessed individual studies risks bias randomeffects metaanalyses supported hypothesis conventional housing significantly exacerbated disease severity medium large effect sizes cancer smd 071 95 ci 054088 cardiovascular disease smd 072 95 ci 035109 stroke smd 087 95 ci 059115 signs anxiety smd 091 95 ci 056125 signs depression smd 124 95 ci 098149 also increased mortality rates hazard ratio 148 95 ci 125174 relative median survival 091 95 ci 089094 metaregressions indicated housing effects ubiquitous across species sexes identify impactful improvements conventional housing data variability assessed via coefficient variation also increased enriched housingconclusionsconventional housing appears sufficiently distressing compromise rodent health raising ethical concerns results also add previous work show research rodents typically cramped cold rotund abnormal malebiased poorly surviving enclosed distressed raising questions validity generalisability data generate research funded nserc canada,0.0
associao entre avaliao clnica e autopercepo da deglutio com escala de incapacidade motora em pacientes com esclerose mltipla codas 2022 jan 10 34 2 e20210026 doi 101590 23171782 20212021026 ecollection 2022purpose investigate association clinical evaluation selfperception deglutition motor disability scale patients multiple sclerosismethods crosssectional prospective study conducted individuals multiple sclerosis treated neuroimmunology outpatient clinic hospital southern brazil reviewed electronic medical records patients extract score last expanded disability status scale analysis inclusion criteria clinical consultation two protocols applied one selfperception risk dysphagia brazilian equivalence instrument eating assessment tool clinical evaluation swallowing food scale gugging swallowing screen data analyzed tables descriptive statistics tests fishers exact association test chisquare test assess association results applied scales considered maximum significance level 5 p 005 results possible observe significant association scores gugging swallowing screen scales expanded disability status scale patients addition also relation results protocols expanded disability status scaleconclusion patients multiple sclerosis study presented oropharyngeal dysphagia confirmed association clinical evaluation swallowing results instrument selfperception swallowing motor disability scale,0.0
therapy switches fingolimodtreated patients multiple sclerosis longterm experience german ms registry neurol ther 2022 jan 12 doi 101007 s4012002100320w online ahead printabstractintroductions therapy switches patients multiple sclerosis ms receiving treatment fingolimod occur frequently clinical practice well represented realworld data aim study identify characterize treatment switches reveal sociodemographic clinical changes time fingolimodtreated people ms pwms methods data 2536 fingolimodtreated pwms extracted german ms registry different time periods analyzed 20102019 results overall 283 pwms treatmentnave fingolimod initiation interferon beta 307 common prefingolimod treatment ocrelizumab 198 frequent subsequent treatment 944 patients fingolimod switched 2010 2019 median disease duration fingolimod initiation decreased 85 71 years p 0001 patients taking fingolimod 1 year treatment initiation decreased 896 805 p 0001 females p 0001 young patients p 0003 showed shorter time fingolimod frequent reason switching disease activity relapse mri despite treatment annualized relapse rate increased 037 patients fingolimod 047 treatment cessation decreasing 019 treatment subsequent diseasemodifying drug dmd initiatedconclusion treatment switches fingolimod subsequent dmds currently occur shorter treatment durations 10 years ago possibly due growing treatment spectrum planning adequate washout periods essential done individualized basispmid35020157 doi101007 s4012002100320w,0.0
reliability televisits patients mild relapsingremitting multiple sclerosis covid19 era neurol sci 2022 jan 11 doi 101007 s10072022058685 online ahead printabstractbackground evidence costeffectiveness telemedicine tm management multiple sclerosis ms provided recently however doubts persist accuracy neurological examinations performed remotelyobjectives study investigated reliability neurological evaluations performed tm mild ms patients compared standard inperson visitsmethods total 76 patients relapsingremitting ms expanded disability status scale edss 35 consecutively recruited 40 patients 526 accepted undergo inperson tm evaluations independent examiners within 48 h alternatively asked patients assure presence caregiver tm visits satisfaction questionnaire administered participantsresults interrater agreement attributed two independent neurologists tm visit high 080 edss functional systems fs scores moderate agreement tm inperson evaluations emerged pyramidal 057 p 0001 brainstem 057 p 0001 bowel bladder 054 p 0001 sensory 051 p 0001 fs scores higher patients providing support caregiver good reliability reported edss scores computed remote inperson visits icc 083 95 ci 070091 p 0001 conclusions despite complexity neurological examination tm useful monitoring ms patients low disabilitypmid35018548 doi101007 s10072022058685,0.0
quantification human plasma metalloproteins multiple sclerosis ischemic stroke healthy controls reveals association haptoglobinhemoglobin complexes age plos one 2022 jan 12 17 1 e0262160 doi 101371 journalpone0262160 ecollection 2022abstractadvanced analytical methods play important role quantifying serum disease biomarkers problem separating thousands proteins can reduced analyzing subproteome metalloproteome defined proteins contain bound metals employed size exclusion chromatography sec coupled inductively coupled plasma atomic emission spectrometer icpaes analyze plasma multiple sclerosis ms participants n 21 acute ischemic stroke ais participants n 17 healthy controls n 21 fe cu znmetalloproteins using anova analysis compare mean peak areas among groups revealed statistically significant differences ceruloplasmin p 031 2macroglobulin p 051 transferrin p 031 however statistically significant difference observed haptoglobinhemoglobin hphb complex p 004 driven difference control group ais p 0012 ms group p 013 based dunnes test linear regression model hphb complex groups now adjusted age found statistically significant differences groups p 095 suggestive age p 0057 measure strength association hphb complex age without possible modifications due disease calculated spearman rank correlation healthy controls latter revealed positive association r 039 95 confidence interval 005 083 suggests either removal hphb complexes blood circulation slows age release hb red blood cells increases age also observed fepeak corresponding hphb complex eluted 100 s later 14 study samples correlated age disease diagnosis consistent presence smaller hp 11 isoform 15 populationpmid35020753 doi101371 journalpone0262160,0.0
seroconversion following covid19 vaccination can optimize protective response cd20treated individuals clin exp immunol 2021 nov 18uxab015 doi 101093 cei uxab015 online ahead printabstractalthough everincreasing number diseasemodifying treatments relapsing multiple sclerosis ms appear influence covid19 severity concern use anticd20depleting monoclonal antibodies due apparent increased risk severe disease following sarscov2 infection inhibition protective anticovid19 vaccine responses antibodies given maintenance infusions injections cause persistent depletion cd20+ b cells notably memory b cell populations may instrumental control relapsing ms however also continuously deplete immature mature nave b cells form precursors infectionprotective antibody responses thus blunting vaccine responses seroconversion maintained sarscov2 neutralizing antibody levels provide protection covid19 however evident poorseroconversion occurs majority individuals following initial booster covid19 vaccinations based standard 6monthly dosing intervals seroconversion may optimized anticd20treated population vaccinating prior treatmentonset using extended delayed interval dosing 36 month extension dosing interval established therapy b cell monitoring 13 b cell repopulation occurs prior vaccination people will take year replete therefore protection may depend either vaccineinduced t cell responses typically occur may require prophylactic rapid postinfection therapeutic antibody small molecule antiviral treatment optimise protection covid19 studies warranted demonstrate safety efficacy approaches whether immunity wanes prematurely observed populationspmid35020857 doi101093 cei uxab015,0.0
assessment natural language processing methods ascertaining expanded disability status scale score electronic health records patients multiple sclerosis algorithm development validation study jmir med inform 2022 jan 12 10 1 e25157 doi 102196 25157abstractbackground expanded disability status scale edss score widely used measure monitor disability progression people multiple sclerosis ms however extracting deriving edss score unstructured electronic health records can timeconsumingobjective aimed compare rulebased deep learning natural language processing algorithms detecting predicting total edss score edss functional system subscores electronic health records patients msmethods studied 17 452 electronic health records 4906 ms patients followed one canadas largest ms clinics june 2015 july 2019 randomly divided records training 80 test 20 data sets compared performance characteristics 3 natural language processing models first applied rulebased approach extracting edss score sentences containing keyword edss next trained convolutional neural network cnn model predict 19 halfstep increments edss score finally used combined rulebasedcnn model approach determined accuracy precision recall fscore compared reference standard manually labeled edss scores clinic databaseresults overall combined keywordcnn model demonstrated best performance accuracy precision recall fscore 090 083 083 083 respectively respective figures rulebased cnn models individually 057 091 065 070 086 070 070 070 missing data model performance edss subscores lower total edss score performance improved considering notes known values edss subscoresconclusions combined keywordcnn natural language processing model can extract accurately predict edss scores patient records approach can automated efficient information extraction clinical research settingspmid35019849 doi102196 25157,0.0
effect cervical mobilization balance static plantar loading distribution patients multiple sclerosis randomized crossover study neurosciences riyadh 2022 jan 27 1 3139 doi 1017712 nsj2022120210099abstractobjectives investigate influence repeated cervical mobilization cm balance plantar loading distribution patients multiple sclerosis ms methods total 12 individuals included cross study designed cross sectional study carried october 2019 july 2020 individuals received traditional treatment tm cervical mobilization treatments cm 2 days week 4 weeks different order random method treated joint traction sliding techniques soft tissue mobilization techniques myofascial relaxation applied cm addition tm romberg test rt sharpened romberg test srt functional reach test frt used balance assessment plantar loading distribution evaluated pedobarography maximum mean pressure foot percentages pressure values fore rear foot percentages bodyweight discharge onto right feet left feet recordedresults forefoot loading increased treatment cm group p005 duration rt srt increased average pressure decreased cervical mobilization group p005 body weight discharge onto right feet left feet approached 50 cervical mobilization p005 conclusions cervical mobilization techniques can positively change balance plantar loading distribution compared traditional treatment cervical mobilization applications used support neurological rehabilitationpmid35017288 doi1017712 nsj2022120210099,0.0
translocator protein ligand piga1138 reduces disease symptoms severity experimental autoimmune encephalomyelitis model primary progressive multiple sclerosis mol neurobiol 2022 jan 11 doi 101007 s12035022027372 online ahead printabstractmultiple sclerosis ms autoimmune demyelinating disease central nervous system cns caused cns infiltration peripheral immune cells immunemediated attack myelin sheath neuroinflammation axonal neuronal dysfunctions drugs available cope relapsingremitting ms rrms therapy primary progressive ms ppms growing evidence supports regulatory role translocator protein tspo neuroinflammatory demyelinating neurodegenerative processes investigated therapeutic potential phenylindolyilglyoxylamydes pigas tspo ligands myelin oligodendrocyte glycoprotein mog induced experimental autoimmune encephalomyelitis eae mice mimicking human ppms mogeae c57bl 6mice treated tspo ligands piga839 piga1138 vehicle several methods combined evaluate pigastspo ligand effects mogeae symptoms cns infiltration immune cells demyelination axonal damages piga1138 15 mg kg drastically reduced mogeae mice clinical scores ameliorated motor dysfunctions assessed catwalk device counteracted mogeaeinduced demyelination preserving myelin basic protein mbp expression cns furthermore piga1138treatment prevented eaeevoked decreased neurofilament200 expression spinal cerebellar axons moreover piga1138 inhibited peripheral immunecd45 + cell infiltration cns suggesting may control inflammatory mechanisms involved ppms concordantly piga1138 enhanced antiinflammatory interleukin10 serum level mogeae mice piga1138treatment increased neurosteroid allopregnanolone production ameliorated pathological biomarkers piga839 unable activate neurosteroidogenesis vivo exerted moderate partial effects mogeae mice altogether results suggest piga1138based treatment may represent interesting possibility explored innovation effective therapies ppmspmid35018577 doi101007 s12035022027372,1.0
trafficgenerated air pollution exposure mediated expression factors associated demyelination female apolipoprotein e#x2f mouse model neurotoxicol teratol 2022 jan 8107071 doi 101016 jntt2022107071 online ahead printabstractepidemiology studies suggest exposure ambient air pollution associated demyelinating diseases central nervous system cns including multiple sclerosis ms pathophysiology ms results autoimmune response involving increased inflammation demyelination cns higher young adult females exposure trafficgenerated air pollution associated neuroinflammation detrimental outcomes cns however role progression pathologies associated demyelinating diseases yet fully characterized female model thus investigated effects inhalation exposure mixed vehicle emissions mve brains ovaryintact ov+ ovariectomized ov female apolipoprotein apoe mice ov + ov apoe mice exposed via wholebody inhalation either filtered air fa controls mixed gasoline diesel vehicle emissions mve 200 pm g m3 6 h d 7 d wk 30 d analyzed mveexposure mediated alterations myelination presence cd4+ cd8+ t cells reactive oxygen species ros myelin oligodendrocyte protein mog expression estrogen er er progesterone proa b receptors cns mveexposure mediated significant alterations myelination across multiple regions cerebrum well increased cd4+ cd8+ staining also increase ros production cns mveexposed ov ov + apoe mice ov mice displayed reduction cerebral er mrna expression compared ov + mice however mve exposure resulted even decrease er expression er pro b unchanged across groups findings collectively suggest inhaled mveexposure may mediate estrogen receptor expression alterations associated increased cd4+ cd8+ infiltration regional demyelination ros production cns female apoe micepmid35016995 doi101016 jntt2022107071,1.0
calorie restriction dietary restriction far can protect brain neurodegenerative diseases neural regen res 2022 aug 17 8 16401644 doi 104103 16735374332126abstractfinding correct nutritional intervention one biggest challenges treating patients neurodegenerative diseases general patients develop strong metabolic alterations resulting lower treatment efficacy higher mortality rates however still many open questions regarding effectiveness dietary interventions neurodiseases studies shown reduction calorie intake activates key pathways might important preventing slowing progression diseases however still unclear whether neuroprotective effects associated overall reduction calories hypocaloric diet specific nutrient restriction diet restriction therefore discuss commonly differently hypocaloric restricted diets modulate signaling pathways changes can protect brain neurodegenerative diseasespmid35017409 doi104103 16735374332126,1.0
adherence persistence diseasemodifying therapies multiple sclerosis 24 months retrospective claims analysis neurol ther 2022 jan 12 doi 101007 s40120021003193 online ahead printabstractintroduction sought assess adherence persistence ocrelizumab ocr compared diseasemodifying treatments dmts route administration roa multiple sclerosis ms 24 months united statesmethods retrospective claims analysis ms patients initiating new dmt conducted using ibm marketscan commercial medicare supplemental databases april 2016 december 2019 continuous enrollment 12 months 24 months initiating index dmt required adherence assessed based proportion days covered pdc followup period values 80 considered adherent persistence defined evidence switching another dmt gap 60 days dmt coverageresults total 1710 patients 24 months followup ocr n 524 oral n 701 injectable n 365 intravenous iv n 120 included patients initiating ocr higher adherence 80 vs 55 35 54 oral injectable iv respectively persistence 75 vs 54 33 55 respectively 24 months relative risks rrs 24month nonadherence initiating orals injectables ivs 22 95 ci 1729 30 95 ci 2240 22 95 ci 1533 respectively compared initiating ocr similarly patients receiving orals injectables ivs rr 19 95 ci 1424 25 95 ci 1934 18 95 ci 1226 24month discontinuation respectively similar patterns observed 12 18 monthsconclusions patients initiating ocr realworld setting achieved higher rates adherence persistence 24 months compared initiating dmts consistent published literature showing similar results 12 18 months optimizing medication adherence persistence fundamental ms care clinicians consider elements dmts may improve compliancepmid35020156 doi101007 s40120021003193,0.0
freewater diffusion tensor imaging detects occult periependymal abnormality aqp4iggseropositive neuromyelitis optica spectrum disorder sci rep 2022 jan 11 12 1 512 doi 101038 s41598021044903abstractto compare freewater corrected diffusion tensor imaging dti measures normalappearing periependymal area aqp4iggseropositive nmosd multiple sclerosis ms investigate occult pathophysiology prospective study included 44 patients mean age 3952 1190 years 14 men aqp4iggseropositive nmosd n 20 ms n 24 underwent dti april 2014 april 2020 based freewater corrected dti measures obtained normalappearing periependymal voxels 1 lateral ventricles 2 3rd 4th ventricles dependent variables mancova conducted compare two groups using clinical variables covariates significant difference found aqp4iggseropositive nmosd ms 3rd 4th periependymal voxels 0462 p 0001 fractional anisotropy axial diffusivity significantly decreased radial diffusivity increased aqp4iggseropositive nmosd posthoc analysis compared ms f 27616 p 0001 f 7336 p 0011 f 5800 p 0022 respectively freewater corrected dti measures differ periependymal area surrounding diencephalon brain stem cerebellum ms nmosd may suggest occult white matter injury areas distribution aqp4 nmosdpmid35017589 doi101038 s41598021044903,0.0
potential role bay117082 nfb blocker inhibiting experimental autoimmune encephalomyelitis c57bl#x2f 6j mice via declining nlrp3 inflammasomes clin exp immunol 2021 nov 27uxab022 doi 101093 cei uxab022 online ahead printabstractmultiple sclerosis ms inflammatory autoimmune demyelinating disease central nervous system nodlike receptor pyrin domaincontaining 3 nlrp3 inflammasome implicated pathogenesis ms animal model experimental autoimmune encephalomyelitis eae however exact mechanism nlrp3 inflammasome involved development ms eae clear nfkappab nfb associated activity nlrp3 inflammasomes role nfb controversial sought demonstrate nfb nlrp3 contribute development ms eae nfb pathway positively correlated nlrp3 activation eae inhibitor nfb nlrp3 bay117082 can prevent treat eae bay117082 5mg kg ip 20 mg kg ip intraperitoneally administered eae mice time second injection pertussis toxin bay117082 prevention group onset symptoms bay117082 treatment group mrna expressions nlrp3 determined qpcr protein expressions nlrp3 nfbp65 phosphorylatedp65 determined western blotting serum levels inflammatory cytokines measured cytometric bead array mice treated bay117082 prevention treatment groups showed lower clinical scores attenuated pathological changes nlrp3 inflammasome activity nfb spinal cord eae mice higher control group however level nlrp3 inflammasome decreased bay117082 prevention treatment groups bay117082 promising therapeutic agent ms nlrp3 activation eae maybe related nfb pathwaypmid35020839 doi101093 cei uxab022,1.0
characterization radioiodinated diaryl oxadiazole derivatives spect probes detection myelin multiple sclerosis acs chem neurosci 2022 jan 12 doi 101021 acschemneuro1c00753 online ahead printabstractmultiple sclerosis ms intractable disease central nervous system results destruction myelin sheath direct measurement de remyelination required monitoring disease stage ms useful method established study characterized four diaryl oxadiazole derivatives novel myelinimaging probes single photon emission computed tomography spect diaryl oxadiazole derivatives penetrated bloodbrain barrier normal mice among highest ratio radioactivity accumulation white matter myelinrich region gray matter myelindeficient region observed 60 min postinjection 125i 1 3 4podpdm ex vivo autoradiography using normal mice blocking study ex vivo autoradiography radioactivity accumulation 125i 1 3 4podpdm white matter markedly reduced 125i 1 3 4podpdm detected demyelination ex vivo autoradiographic images spinal cord experimental autoimmune encephalomyelitis mice also brain lysophosphatidylcholine lpc injection addition 123i 1 3 4podpdm image lpcinduced demyelination mouse brain spect results suggest 123i 1 3 4podpdm may potential spect probe imaging myelin mspmid35019269 doi101021 acschemneuro1c00753,1.0
side effects occurred early people multiple sclerosis first year treatment cladribine tablets plain language summary neurodegener dis manag 2022 jan 12 doi 102217 nmt20210041 online ahead printabstractpeople multiple sclerosis also shortened ms may difficulties staying treatment due side effects cladribine tablets approved treating relapsing forms ms given mouth four short periods two years benefit convenient dosing may lost side effects prevent people ms finishing treatment summary study examined side effects cladribine tablets treatment first 12 weeks two clinical studies called clarity oraclems overall 347 participants took cladribine tablets experienced drugrelated side effects compared 232 participants took placebo side effects mild seen 548 participants taking cladribine tablets 591 taking placebo low number participants discontinued treatment due side effects 16 participants took cladribine tablets 14 participants took placebo researchers concluded cladribine tablets welltolerated people ms likely complete full treatment course clinicaltrialsgov nct numbers clarity study nct00213135 oraclems study nct00725985pmid35019731 doi102217 nmt20210041,0.0
determinants longterm opioid prescribing urban population cross sectional study br j clin pharmacol 2022 jan 11 doi 101111 bcp15231 online ahead printabstractbackground opioid prescribing doubled uk 1998 2016 potential adverse health implications include dependency falls increased health expenditureaim describe predictors longterm opioid prescribing ltop 3 opioid prescriptions 90day period design setting retrospective crosssectional study 41 general practices south londonmethod multilevel multivariable logistic regression investigate determinants ltopresults 2 679 08 320 639 registered patients 18 years identified ltop patients likely ltop 5 long term conditions ltcs adjusted odds ratio aor 365 95 confidence interval ci 304438 24 ltcs aor 138 ci 119161 comparison ltcs 75 years compared 1824 years aor 1231 ci 71215 smokers compared nonsmokers aor 22 ci 2025 females compared males aor 19 ci 1720 deprived deprivation quintile aor 16 ci 1418 compared least deprived separate model examining individual longterm conditions ltcs strongest associations ltop noted sickle cell disease scd aor 184 ci 128264 osteoarthritis aor 30 ci 2833 rheumatoid arthritis aor 28 ci 2234 depression aor 26 ci 2328 multiple sclerosis 25 ci 1444 conclusion ltop significantly higher aged 75 years multimorbidity specific ltcs sickle cell disease osteoarthritis rheumatoid arthritis depression multiple sclerosis characteristics may enable design targeted interventions reduce ltoppmid35018644 doi101111 bcp15231,0.0
type interferons autoimmunity j invest dermatol 2022 jan 8s0022202x 21 026063 doi 101016 jjid202111031 online ahead printabstractdysregulated ifn1 responses play crucial roles development multiple forms autoimmunity many patients lupus systemic sclerosis sjogrens syndrome dermatomyositis demonstrate enhanced ifn1 signaling ifn1 excess associated disease severity autoantibodies potentially predict response newer therapies targeting ifn1 pathways review provide overview signaling pathway immune functions ifn1s health disease also review systemic autoimmune diseases classically associated ifn1 upregulation current therapeutic strategies targeting ifn1 systempmid35016780 doi101016 jjid202111031,0.0
atypical antipsychotics multiple sclerosis review vivo immunomodulatory effects abstractintroductionthe high efficacy atypical antipsychotics aap treating diverse psychiatric disorders partly attributed capacity curb neuroinflammation shared aspect diseases immunomodulatory properties aap lately explored context multiple sclerosis ms autoimmune demyelinating disease cnsmethodsthis study aimed review vivo studies reporting therapeutic effects aap eae main animal model ms cuprizoneinduced demyelination matter conducted literature search screening process eventually yielded 8 eligible studiesresultsall studies agreed efficiency aap dramatically reduce eae severity delay onset suppressing production numerous inflammatory cytokines clozapine showcased similar yet intense effects risperidone quetiapine olanzapine significantly attenuating cd4 t cell infiltration myeloid cell activation upregulating tregs clozapine also downregulated chemokines responsible migration immune cells cns caused dopamine receptor levels brain eae mice risediscussiontaken together findings unanimously attest antiinflammatory immunomodulatory properties aap suggesting therapeutic potential expands beyond current neuropsychiatric applications despite salutary effects aap ms reported vivo clinical trial clozapine ms patients failed confirm preclinical findings due low acceptability aap early participant withdrawalconclusionalthough preclinical evidence unquestionably supports multifaceted beneficial properties aap ms investigation required elucidate pharmacodynamic profile agents allow proper clinical testing ms patients,1.0
diagnosis multiple sclerosis progress confusion available,0.0
neuroimmunological investigations cerebrospinal fluid patients recent onset depression study protocol background proinflammatory response suggested involved pathophysiology depression subgroup patients however comprehensive largescale studies neuroimmunological investigations cerebrospinal fluid csf lacking largescale longitudinal csf studies comparing patients depression healthy controls currently existmethodsa longitudinal casecontrol study including least 100 patients first time depression icd10 f32 within past year ongoing symptoms least 100 sex age matched healthy controls collection csf blood fecal samples individuals will evaluated neurological examination including neurological soft signs interviewed psychopathology assessment symptomatology evaluated relevant rating scales level functioning quality life will evaluated panel interview questions rating scales cognitive function assessed relevant test battery addition large number potential confounders will registered bmi smoking status current medication etc primary outcomes csf white cell count csf serum albumin ratio csf total protein levels igg index csf levels il6 il8 prevalence cnsreactive autoantibody csf blood secondary outcomes exploratory analyses wide range neuroimmunological markers specific autoantibodies power calculations computed primary outcomes based previous csf studies including patients depression healthy controlsdiscussionthis study will represent hitherto largest investigation csf patients recent onset depression compared healthy controls expect elucidate neuroimmunological alterations individuals depression characterize immunological profile paving way development effective treatments based biomarkerstrial registrationthe study approved regional committee health research ethics capital region jno h16030985 danish data protection agency jno rhp2016020 isuite 04945,0.0
eligibility criteria pediatric patients may benefit anti sarscov2 monoclonal antibody therapy administration italian intersociety consensus statement abstractthe fast diffusion sarscov2 pandemic called equally rapid evolution therapeutic optionsthe human recombinant monoclonal antibodies mabs recently approved food drug administration fda italian medicines agency aifa subjects aged 12 sarscov2 infection specific risk factorscurrently indications specific use two different mabs combination bamlanivimab+etesevimab produced eli lilly casirivimab+imdevimab produced regeneron drugs shown favorable effects adult patients initial phase infection whereas date data available use childrenaifa criteria derived existing literature reports increased risk severe covid19 children comorbidities however studies analyzing determinants progression severe disease mainly monocentric limited numbers reporting mostly generic risk categoriesthus italian society pediatrics invited affiliated scientific societies produce consensus document based revision criteria proposed aifa light recent literature experts agreementthis consensus tries detail patients actually risk develop severe disease analyzing common comorbidities children order detail indications mabs administration guide clinicians identifying eligible patients,0.0
sublethal enteroviral infection exacerbates disease progression als mouse model background amyotrophic lateral sclerosis als fatal neurodegenerative disease motor neuron system associated genetic environmental risk factors infection enteroviruses including poliovirus coxsackievirus coxsackievirus b3 cvb3 proposed possible causal risk factor als due evidence enteroviruses can target motor neurons establish persistent infection central nervous system cns recent findings enteroviral infectioninduced molecular pathological phenotypes closely resemble als however causal relationship yet affirmedmethodswildtype c57bl 6j g85r mutant superoxide dismutase 1 sod1g85r als mice intracerebroventricularly infected sublethal dose cvb3 shaminfected subset mice ribavirin broadspectrum antirna viral drug given subcutaneously acute chronic stage infection following viral infection general activity survival monitored daily week 60 starting week 20 postinfection pi motor functions measured weekly mouse brains spinal cords harvested day 10 week 20 week 60 pi histopathological evaluation neurotoxicity immunohistochemical staining viral protein neuroinflammatory immune als pathology markers nanostring rtqpcr analysis inflammatory gene expressionresultswe found sublethal infection mimicking chronic infection sod1g85r als mice cvb3 resulted early onset progressive motor dysfunction shortened lifespan similar viral infection c57bl 6j background strain sod1g85r mice significantly affect motor function mortality compared mock infection within timeframe current study 60 weeks pi furthermore showed cvb3 infection led significant increase proinflammatory gene expression immune cell infiltration induced alsrelated pathologies ie tar dnabinding protein 43 tdp43 pathology neuronal damage cns sod1g85r c57bl 6j mice finally discovered early day 1 late day 15 administration ribavirin rescue alslike neuropathology symptoms induced cvb3 infectionconclusionsour study identifies new risk factor contributes early onset accelerated progression als offers opportunities development novel targeted therapies,0.0
new promising therapeutic avenues curcumin brain diseases molecules 2021 dec 31 27 1 236 doi 103390 molecules27010236abstractcurcumin dietary polyphenol isolated curcuma longa turmeric commonly used herb spice worldwide biopharmacological effects curcumin also called spice life fact recognized curcumin possesses important proprieties antioxidant antiinflammatory antimicrobial antiproliferative antitumoral antiaging neurodegenerative diseases alzheimers diseases parkinsons diseases multiple sclerosis group diseases characterized progressive loss brain structure function due neuronal death present effective treatment cure diseases protective effect curcumin neurodegenerative diseases proven vivo vitro studies current review highlights latest findings neuroprotective effects curcumin bioavailability mechanism action possible application prevention treatment neurodegenerative disorderspmid35011468 doi103390 molecules27010236,1.0
vitamin d depressive symptoms adults multiple sclerosis scoping review int j environ res public health 2021 dec 25 19 1 199 doi 103390 ijerph19010199abstractbackground vitamin d deficiency correlated multiple sclerosis ms risk disease activity controversy whether vitamin d impact depressive symptoms people ms pwms aim scoping review evaluate association vitamin d status depressive symptoms pwmsmethods searched databases include studies published march 2021 provide overview available evidence correlation vitamin d status depressive symptoms pwms eligibility criteria follows studies evaluating use vitamin d measurement depressive symptoms patients suffering ms including randomized nonrandomized studies studies written english studies exploring adult population age 18results eleven studies met inclusion criteria two abstracts majority crosssectional studies two prospective longitudinal studies one retrospective cohort study one randomized placebocontrolled trial rct eleven studies selected seven showed potential correlation low vitamin d levels depressive symptomsconclusion future rct studies include patients greater severity depressive symptoms consider confounding factors sun exposure seasonal variation vitamin dpmid35010459 doi103390 ijerph19010199,0.0
retinoid x receptor cellular biochemical roles nuclear receptor focus neuropathological involvement mol neurobiol 2022 jan 11 doi 101007 s1203502102709y online ahead printabstractretinoid x receptors rxrs present subgroup nuclear receptor superfamily particularly high evolutionary conservation ligand binding domain receptor exists isotypes form homo heterodimeric complexes permissive nonpermissive receptors research identified biochemical roles several nuclear receptor family members roles rxrs various neurological disorders remain relatively underinvestigated rxr acts ligandregulated transcription factor modulating expression genes plays critical role mediating several developmental metabolic biochemical processes cumulative evidence indicates abnormal rxr signalling affects neuronal stress neuroinflammatory networks several neuropathological conditions protective effects targeting rxrs pharmacological ligands established various cell animal models neuronal injury including alzheimer disease parkinson disease glaucoma multiple sclerosis stroke review summarises existing knowledge roles rxr interacting partners ligands cns disorders future research will determine importance structural functional heterogeneity amongst various rxr isotypes well elucidate functional links rxr homo heterodimers specific physiological conditions increase drug targeting efficiency pathological conditionspmid35015251 doi101007 s1203502102709y,0.0
assessing diagnosis disclosure concealment multiple sclerosis building framework moving forward mult scler 2022 jan 1113524585211069668 doi 101177 13524585211069668 online ahead printno abstractpmid35014561 doi101177 13524585211069668,0.0
immunological causes obsessivecompulsive disorder time concept quot autoimmune ocdquot subtype transl psychiatry 2022 jan 10 12 1 5 doi 101038 s41398021017004abstractobsessivecompulsive disorder ocd highly disabling mental illness can divided frequent primary rarer organic secondary forms association secondary autoimmune triggers introduced discovery pediatric autoimmune neuropsychiatric disorder associated streptococcal infection pandas pediatric acute onset neuropsychiatric syndrome pans autoimmune encephalitis systemic autoimmune diseases autoimmune brain diseases multiple sclerosis also reported sometimes present obsessivecompulsive symptoms ocs subgroups patients ocd show elevated proinflammatory cytokines autoantibodies targets include basal ganglia conceptual review paper clinical manifestations pathophysiological considerations diagnostic investigations treatment approaches immunerelated secondary ocd summarized novel concept autoimmune ocd proposed small subgroup ocd patients clinical signs based pandas pans criteria recent experience autoimmune encephalitis autoimmune psychosis suggested red flag signs autoimmune ocd include sub acute onset unusual age onset atypical presentation ocs neuropsychiatric features eg disproportionate cognitive deficits accompanying neurological symptoms eg movement disorders autonomic dysfunction treatment resistance associations symptom onset infections group streptococcus comorbid autoimmune diseases malignancies clinical investigations may also reveal alterations increased levels antibasal ganglia dopamine receptor antibodies inflammatory changes basal ganglia neuroimaging based red flag signs criteria possible probable definite autoimmune ocd subtype proposedpmid35013105 doi101038 s41398021017004,0.0
phase 1 study gdc0134 dual leucine zipper kinase inhibitor als ann clin transl neurol 2022 jan 10 doi 101002 acn351491 online ahead printabstractobjective dual leucine zipper kinase dlk regulates cjun nterminal kinase pathway involved axon degeneration apoptosis following neuronal injury potential therapeutic target amyotrophic lateral sclerosis als firstinhuman study investigated safety tolerability pharmacokinetics pk oral gdc0134 smallmolecule dlk inhibitor plasma neurofilament light chain nfl levels explored gdc0134treated als patients dlk conditional knockout cko micemethods study included placebocontrolled single multiple ascendingdose sad mad stages openlabel safety expansion ole adaptive dosing 48 weeksresults fortynine patients enrolled gdc0134 1200 mg daily well tolerated sad mad stages serious adverse events saes ole three study drugrelated saes occurred thrombocytopenia dysesthesia grade 3 optic ischemic neuropathy grade 4 grade 2 sensory neurological aes led dose reductions discontinuations gdc0134 exposure doseproportional median halflife 84 h patients showed gdc0134 exposuredependent plasma nfl elevations dlk cko mice also exhibited plasma nfl compared wildtype littermatesinterpretation trial characterized gdc0134 safety pk adequately tolerated dose identified nfl elevations gdc0134treated patients dlk cko mice raised questions interpretation biomarkers affected disease ontarget drug effects safety profile gdc0134 considered unacceptable led discontinuation drug development als work necessary understand relationships neuroprotective potentially therapeutic effects dlk knockout inhibition nfl changes patients alspmid35014217 doi101002 acn351491,1.0
cannabinoids breast cancer differential susceptibility according subtype molecules 2021 dec 28 27 1 156 doi 103390 molecules27010156abstractalthough cannabinoids used centuries diverse pathological conditions recently clinical interest application emerged due diverse pharmacological properties indeed well established cannabinoids exert important actions multiple sclerosis epilepsy pain relief regarding cancer cannabinoids first introduced manage chemotherapyrelated side effects though several studies demonstrated modulate proliferation death different cancer cells well angiogenesis making attractive agents cancer treatment relation breast cancer suggested estrogen receptornegative er cells sensitive cannabinoids estrogen receptorpositive er+ cells fact studies regarding effects breast tumors conducted triplenegative breast cancer tnbc nonetheless number studies human epidermal growth factor receptor 2positive her2+ er+ breast tumors rising recent years however besides optimistic results obtained thus far still long way go fully understand role molecules review intends help clarify clinical potential cannabinoids breast cancer subtypepmid35011388 doi103390 molecules27010156,0.0
early diagnosis multiple sclerosis using sweptsource optical coherence tomography convolutional neural networks trained data augmentation sensors basel 2021 dec 27 22 1 167 doi 103390 s22010167abstractbackground aim paper implement system facilitate diagnosis multiple sclerosis ms initial stages using convolutional neural network cnn classify images captured sweptsource optical coherence tomography ssoct methods ssoct images 48 control subjects 48 recently diagnosed ms patients used images show thicknesses 45 60 points following structures complete retina retinal nerve fiber layer two ganglion cell layers gcl+ gcl++ choroid cohen distance used identify structures regions within greatest discriminant capacity original database oct images augmented deep convolutional generative adversarial network expand cnns training setresults retinal structures greatest discriminant capacity gcl++ 4499 image points complete retina 2671 gcl+ 2293 thresholding images using inputs cnn comprising two convolution modules one classification module obtains sensitivity specificity 10conclusions feature preselection use convolutional neural network may promising nonharmful lowcost easytoperform effective means assisting early diagnosis ms based ssoct thickness datapmid35009710 doi103390 s22010167,0.0
pustular psoriasis following treatment multiple sclerosis clin exp dermatol 2022 jan 11 doi 101111 ced15100 online ahead printno abstractpmid35014707 doi101111 ced15100,0.0
highresolution quantitative mri multiple sclerosis spinal cord lesions magn reson med 2022 jan 11 doi 101002 mrm29152 online ahead printabstractpurpose validation quantitative mr measures myelin imaging postmortem multiple sclerosis spinal cordmethods four fixed spinal cord samples imaged first 3t clinical mr scanner identify areas interest scanning 7t small bore scanner using multicomponentdriven equilibrium singlepulse observation t1 t2 protocol produce apparent proton density t1 t2 myelin water intracellular water freewater fraction maps imaging cords sectioned stained histological markers hematoxylin eosin myelin basic protein neurofilament protein quantitatively compared mr mapsresults excellent correspondence found highresolution mr parameter maps histology particularly apparent proton density mri myelin basic protein stainingconclusion highresolution quantitative mri spinal cord provides biologically meaningful measures beneficial diagnose track multiple sclerosis lesions spinal cordpmid35014736 doi101002 mrm29152,1.0
potential contribution il27 il23 gene polymorphisms multiple sclerosis susceptibility association analysis genotype haplotype level j clin med 2021 dec 22 11 1 37 doi 103390 jcm11010037abstract 1 background interleukin 23 il23 interleukin 27 il27 modulate activity t helper 17 cells th17 critical roles autoimmune diseases multiple sclerosis ms genes responsible cytokine generation highly influenced presence single nucleotide polymorphisms snp main regions regulatory sequences promoter regions contributing disease susceptibility evolution present study analyzed associations il23 il27 snps susceptibility multiple sclerosis 2 methods performed casecontrol study including 252 subjects 157 patients diagnosed ms 95 controls used polymerase chain reactionrestriction fragment length polymorphism pcrrflp determine genotypes il27 t4730c rs 181206 il27 a964g rs 153109 il23 receptor gene il23r g1142a rs 11209026 3 results il27t4730c gene polymorphism significantly associated increased odds ms dominant genetic model tc + cc variant genotypes adjusted odds ratio 406 95 ci 214783 pvalue 0000007 qvalue 0000063 individuals carrying il27 a924g variant ag + gg genotype presented higher odds ms compared noncarriers dominant model adjusted 193 95 ci 105351 pvalue 00324 qvalue 005832 allelic genetic model unadjusted pvalue 0015 158 95 ci 109228 il23r381q snp conferred decreased odds ms codominant model inheritance adjusted 026 95 ci 008092 pvalue 00276 qvalue 0058 allelic model unadjusted pvalue 0008 023 95 ci 007075 additive model adjustment age group 40 years vs 40 years sex smoking patients carrying gc a964g t4730c haplotype 318 increased risk 95 ci 174581 p 0001 develop multiple sclerosis 4 conclusions results current study showed significant relationship il27a964g il27t4730c polymorphisms increased risk ms also protective role il23r381q polymorphism moreover haplotypebased analysis proposed mutant gc a924g t4730c significant risk haplotype development mspmid35011777 doi103390 jcm11010037,0.0
mir155 important regulator neuroinflammation int j mol sci 2021 dec 22 23 1 90 doi 103390 ijms23010090abstractmicrornas mirnas small noncoding rna molecules regulate gene expression posttranscriptional level play important role many cellular processes including modulation inflammation mirnas present high concentrations central nervous system cns spatially temporally expressed specific way therefore imbalance expression pattern small molecules can involved development neurological diseases generally cns responds damage disease activation inflammatory response many neurological disorders characterized uncontrolled neuroinflammation many studies support involvement mirnas activation inhibition inflammatory signaling promotion uncontrolled neuroinflammation pathological consequences mir155 proinflammatory mediator cns plays important regulatory role purpose review summarize mir155 regulated pathological consequences deregulation neuroinflammatory disorders including multiple sclerosis alzheimers disease neuroinflammatory disorders modulation mirnas expression used therapeutic strategy treatment pathological neuroinflammationpmid35008513 doi103390 ijms23010090,0.0
toe clearance facilitation improve walking multiple sclerosis effect cyclical focal muscle vibration pm r 2022 jan 10 doi 101002 pmrj12759 online ahead printno abstractpmid35014187 doi101002 pmrj12759,1.0
targeting ahr novel therapeutic modality inflammatory diseases int j mol sci 2021 dec 28 23 1 288 doi 103390 ijms23010288abstractfor decades activation aryl hydrocarbon receptor ahr excluded consideration therapeutic approach due potential toxic effects ahr ligands induction cytochrome p450 enzyme cyp1a1 following ahr activation however now understood ahr activation serves environmental sensor regulates effects environmental toxins also key immunomodulator ligands induce variety cellular epigenetic mechanisms attenuate inflammation thus emergence indepth research diverse groups compounds capable activating receptor prompted reconsideration use therapeutically aim review summarize body research surrounding ahr role regulating inflammation specifically evidence supporting potential targeting receptor modulate immune response inflammatory autoimmune diseases will highlighted additionally opportunities challenges developing ahrbased therapies suppress inflammation will discussedpmid35008717 doi103390 ijms23010288,0.0
tcell response varicella zoster virus patients multiple sclerosis relapse remission int j mol sci 2021 dec 28 23 1 298 doi 103390 ijms23010298abstractan association varicella zoster virus vzv multiple sclerosis ms reported mexican populations aim study compare response t cells ms patients relapse remission vitro stimulation vzv adenovirus av epsteinbarr virus ebv proliferation cytokine secretion t cells 29 relapsingremitting ms patients 38 healthy controls hc analyzed flow cytometry stimulating vzv av ebv igg igm levels vzv ebv quantified using enzymelinked immunosorbent assay relapsing ms patients showed higher percentage responding cd4+ cd8+ t cells vzv compared av hc remitting ms patients proliferation cd4+ t cells higher stimulated vzv compared ebv moreover t cells isolated remitting patients secreted predominantly th1 cytokines cell cultures stimulated vzv finally high concentration antivzv igg found sera patients controls results support previous studies vzvms association particular population studied provide additional information possible role virus pathogenesis mspmid35008726 doi103390 ijms23010298,0.0
brain homogenate decoys antigenspecific cell amplification acs appl bio mater 2021 jan 18 4 1 387391 doi 101021 acsabm0c01048 epub 2020 dec 23abstractmultiple sclerosis complex heterogeneous better tools needed able monitor disease among individuals bloodbased biomarkers often rare profile work developed antigenspecific biomaterials replicate central nervous system niche multiple sclerosis biomarkers amplified incorporated mouse brain homogenate microporous gelatin methacrylate network homogenatecontaining biomaterials differentially stimulated cells led marked amplification diseaserelevant antigenspecific b cells results demonstrate biomaterials containing primary tissue homogenate retain antigen specificity may useful tool decoding human autoimmunitypmid35014289 doi101021 acsabm0c01048,0.0
paratuberculosis hidden killer small ruminants animals basel 2021 dec 21 12 1 12 doi 103390 ani12010012abstractparatuberculosis ptb contagious chronic enteric disease ruminants many nonruminants caused mycobacterium avium subsp paratuberculosis map characterised diarrhoea progressive emaciation consequent serious economic losses due death early culling reduced productivity addition indirect economic losses may arise trade restrictions besides production limiting disease ptb potential zoonosis map isolated crohns disease patients associated human diseases rheumatoid arthritis hashimotos thyroiditis type 1 diabetes multiple sclerosis paratuberculosis sheep goats may globally distributed though information prevalence economic impact many developing countries seem scanty goats susceptible infection sheep species likely develop clinical disease ingestion feed water contaminated faeces mappositive animals common route infection spreads horizontally vertically african countries ptb described neglected disease small ruminants support livelihood people rural areas poor communities disease rarely reported prevention control small ruminants ptb difficult diagnostic assays demonstrate poor sensitivity early disease process addition difficulties identifying subclinically infected animals studies needed provide insight molecular epidemiology transmission impact animals humans socioeconomic aspects prevention control small ruminant ptbpmid35011118 doi103390 ani12010012,0.0
surprising course multiple sclerosis relapse patient sarscov2 vaccination kardiol pol 2022 jan 11 doi 1033963 kpa20220005 online ahead printno abstractpmid35014011 doi1033963 kpa20220005,0.0
optimizing readability format plain language summaries medical research articles crosssectional survey study j med internet res 2022 jan 11 24 1 e22122 doi 102196 22122abstractbackground plain language summaries plss intended provide readers clear nontechnical easily understandable overview medical scientific literature however audience preferences specific pls formats yet fully exploredobjective study aims evaluate preferred readability level format plss medical research articles different disease states via webbased survey audiences different age groupsmethods articles describing phase iii clinical trials published toplevel peerreviewed journals may 2016 may 2018 identified 3 chronic disease states representing range adult patient age groups 1 psoriasis skin disease representative younger patients 2 multiple sclerosis ms neurological disease representative middleaged patients 3 rheumatoid arthritis ra painful joint disease representative older patients four plss developed research article 3 textonly summaries written high medium low complexity 1 infographic evaluate 4 pls formats 20question open survey specific one 3 diseases sent representative sample selected via ukbased patient association websites twitter facebook patient groups weightedaverage calculation applied respondents ranked preferences pls formatresults 3 articles weightedaverage preference scores showed infographic psoriasis 291 ms 271 ra 278 mediumcomplexity textbased pls reading age 1417 years us grade 911 psoriasis 290 ms 247 ra 277 two preferred pls formatsconclusions audience preferences accounted preparing plss accompany peerreviewed original research articles oversimplified text can viewed negatively graphical summaries mediumcomplexity textbased summaries appear popularplain language summary patients caregivers chance read medical research format can understand however know much formats people different illnesses ages prefer researchers wanted find selected 3 medical articles illnesses affect different age groups psoriasis younger patients multiple sclerosis middleaged patients rheumatoid arthritis older patients created 4 summaries article one graphical summary 3 wordsonly summaries high medium low complexity researchers posted surveys uk patient group websites facebook patient groups ask people thought summaries surveys taken 167 people people patients psoriasis multiple sclerosis rheumatoid arthritis caregivers women half university degree illness people preferred graphical summary among wordonly summaries people preferred mediumcomplexity wording written reading age 14 17 years people felt graphical mediumcomplexity summaries clear concise others used jargon simple authors medical articles remember results writing summaries patients research needed preferences people illnesses see multimedia appendix 1 graphical summary plain language summary pmid35014966 doi102196 22122,0.0
role molecular imaging marker remyelination repair multiple sclerosis int j mol sci 2021 dec 31 23 1 474 doi 103390 ijms23010474abstractthe appearance new diseasemodifying therapies multiple sclerosis ms revolutionized ability fight inflammatory relapses immensely improved patients quality life although remarkable achievement carried reducing longterm disability ms clinical disability progression can continue relentlessly irrespective acute inflammation silent disease progression main contributor longterm clinical disability ms results chronic inflammation neurodegeneration repair failure investigating silent disease progression underlying mechanisms challenge standard mri excels depicting acute inflammation lacks pathophysiological lens required targeted exploration molecularbased processes novel modalities utilize nuclear magnetic resonances ability display vivo information imaging look bridge gap displaying cns molecular prism becoming undeniable reality review will focus molecular imaging biomarkers disease progression modalities can harmoniously depict anatomy pathophysiology making attractive candidates become first valid biomarkers neuroprotection remyelinationpmid35008899 doi103390 ijms23010474,1.0
pregnancyinduced brain mri changes women multiple sclerosis eur j neurol 2022 jan 11 doi 101111 ene15245 online ahead printabstractbackground effect pregnancy brain changes radiological disease activity women multiple sclerosis ms well understoodaims describe dynamic lesion activity brain volume changes pregnancy postpartum periodsmethods observational study 62 women relapsingremitting ms included mri 221 scans well clinical visits baseline 24 6 months prepregnancy 6 months postpartum 3 months followup 12 24 months delivery periodresults majority women mild disability short disease duration median 55 years eighteen 290 women relapse year preceding pregnancy onset 9 145 pregnancy 20 323 year following delivery disability status remained unchanged followup women postpartum period n62 higher t2 lesion volume median 094 ml vs 118 ml greater annualized t2 lesion volume increase 00 ml vs 023 ml lower brain parenchymal fraction 864 vs 856 greater annualized brain volume loss 016 vs 174 compared prepregnancy period p0001 1224 months delivery women n41 higher t2 lesion volume 10 ml vs 116 ml lower brain parenchymal fraction 865 vs 860 compared prepregnancy period p0001 conclusions postpartum period associated increase t2 lesion volume accelerated brain volume loss considerable proportion women considered treatment decisionmaking designing clinical trialspmid35015921 doi101111 ene15245,0.0
combination genomic transcriptomic approaches highlights vascular circadian clock components multiple sclerosis int j mol sci 2021 dec 28 23 1 310 doi 103390 ijms23010310abstractaiming exploring vascular components multiple sclerosis ms brain outflow disturbance combined transcriptome analysis ms internal jugular vein ijv wall wes ms families vertical transmission disease main results differential expression ijv wall 16 msgwas genes seven genes grin2a grin2b il20rb il26 per3 pitx2 ppargc1a previously indicated gwas encoding proteins functionally interacting ms candidate gene products strikingly 22 23 genes previously associated vascular neuronal traits diseases nine encoded transcriptional factors regulators six camk2g grin2a grin2b n1rd1 per3 ppargc1a circadian entrainment rhythm components among wes lowfrequency maf 004 snps n 7 filtered 16 genes nr1d1 rs17616365 showed significantly different maf network italian genomes affected cohort 1000 genome project tuscany samples pattern also detected five nonintronic variants grin2b rs1805482 per3 rs2640909 ppargc1a rs2970847 rs8192678 rs3755863 genes coding functional partners overall study proposes specific markers lowfrequency variants might help understand perturbed biological processes vascular tissues contributing ms disease ii characterize ms susceptibility genes functional association diseasepathwayspmid35008743 doi103390 ijms23010310,0.0
ethical practical considerations hiv curerelated research endoflife qualitative interview focus group study united states background one next frontiers hiv research focused finding cure new priority includes people hiv pwh nonaids terminal illnesses willing donate bodies endoflife eol advance search towards hiv cure endeavored understand perceptions research identify ethical practical considerations relevant implementing itmethodswe conducted 20 indepth interviews 3 virtual focus groups among four types key stakeholders united states pwh biomedical hiv cure researchers hiv clinicians bioethicists obtain triangulated viewpoints little known ethics topic group queried ethical considerations safeguards protections conducting hiv curerelated research eol ensure research remains acceptableresultsall four key stakeholder groups generally supported hiv curerelated research conducted eol history altruism within pwh community potential substantial scientific knowledge gained informants expressed 1 strong stakeholder community involvement integral ethical effective implementation well social acceptability research 2 pwh approaching eol inherently considered vulnerable class autonomy must respected choosing participate hiv curerelated research eol 3 greater diversity among study participants well multidisciplinary research teams necessitated hiv curerelated research eol 4 sensitive nature research warrants robust oversight ensure favorable risk benefit balance minimize possibility therapeutic misconception undue influence 5 research protocols remain flexible accommodate participants comfort needs eolconclusionbecause ethical issues presented hiv curerelated research eol robust ethical safeguards utmost importance proposed ethical practical considerations presented herein first step determining best way maximize researchs impact social value much inquiry will need directed towards understanding contextspecific cultural considerations implementing eol hiv cure research diverse settings,0.0
neurapraxia patients trigeminal neuralgia identifiable neurovascular conflict microvascular decompression retrospective analysis 26 cases background microvascular decompression mvd first choice patients classic trigeminal neuralgia tgn sufficiently controlled pharmacological treatment however neurovascular conflict nvc identified mvd patients describe efficacy safety treatment aneurysm clips situationsmethods total 205 patients underwent mvd classic tgn center january 1 2015 december 31 2019 patients without identifiable nvc upon dissection entire trigeminal nerve root neurapraxia performed using yasargil temporary titanium aneurysm clip force 90 g 40 s total 60 s process must suspended temporarily due bradycardia hypertension resultsa total 26 patients median age 64 years 15 women underwent neurapraxia five 26 patients received prior mvd relapsed immediate complete pain relief achieved 26 cases within median followup 3 years range 1060 recurrence noted 3 cases 115 postoperative complications included hemifacial numbness herpes labialis masseter weakness transient dissipated within 36 monthsconclusionsneurapraxia using aneurysm clip safe effective patients classic tgn identifiable nvc mvd whether method developed standardizable method needs investigation,0.0
fruit ripening dynamics integrated analysis carotenoids anthocyanins background fruits vital food resources loaded bioactive compounds varying different stages ripening fruit ripens dynamic color change observed green yellow red due biosynthesis pigments like chlorophyll carotenoids anthocyanins apart making fruit attractive visual indicator ripening status pigments add value ripened fruit making source nutraceuticals industrial products fruit matures undergoes biochemical changes alter pigment composition fruitsresultsthe synthesis degradation retention pathways fruit pigments mediated hormonal genetic environmental factors manipulation underlying regulatory mechanisms fruit ripening suggests ways enhance desired pigments fruits biotechnological interventions report indepth insight dynamics pigment change ripening regulatory mechanisms actionconclusionsthis review emphasizes role pigments asset ripened fruit augment nutritive value antioxidant levels net carbon gain fruits pigments source fruit biofortification tremendous industrial value along tool predict harvest report will great utility harvesters traders consumers natural product divisions extract leading nutraceutical industrial potential preferred pigments biosynthesized different fruit ripening stages,0.0
utilizing mest score prognostic staging iga nephropathy background oxford classification mest score established histopathologic scoring system patients iga nephropathy igan objective study derive prognostic model igan based mest score histopathologic featuresmethodsa total 306 patients biopsyproven primary igan included histopathologic samples retrieved norwegian kidney biopsy registry reclassified according oxford classification study endpoint endstage renal disease esrd patients subclassified three risk models based histologic features model composite score calculated adjusted hazard ratio values model b quartiles model c resultsthe mean followup time 165 years range 02281 total 61 20 patients reached esrd study period univariate analysis m e s t c lesions demonstrated types associated increased risk esrd however multivariate analysis revealed s t c lesions associated poor outcomes statistical analysis 15year data demonstrated models b predictive mest score areaunderthecurve 085 harrel c index values 081 080 mest score models b respectively present cohort adding c lesions mest score improve models prognostic valueconclusionspatients can divided risk classes based mest scores histopathologic data provide valuable prognostic information time diagnosis model b suitable clinical practice userfriendly,0.0
circulating inflammatory cytokines risk five cancers mendelian randomization analysis background epidemiological experimental evidence linked chronic inflammation cancer aetiology unclear whether associations specific inflammatory biomarkers causal due bias order examine whether altered genetically predicted concentration circulating cytokines associated cancer development performed twosample mendelian randomisation mr analysismethodsup 31 112 individuals european descent included genomewide association study gwas metaanalyses 47 circulating cytokines single nucleotide polymorphisms snps robustly associated cytokines located close coding gene cis used instrumental variables inversevariance weighted mr used primary analysis mr assumptions evaluated sensitivity colocalization analyses false discovery rate fdr correction multiple comparisons applied corresponding germline gwas summary data five cancer outcomes breast endometrial lung ovarian prostate subtypes selected largest cancerspecific gwass available cases ranging 12 906 endometrial 133 384 breast cancer resultsthere evidence inverse associations macrophage migration inhibitory factor breast cancer per sd 088 95 ci 083 094 interleukin1 receptor antagonist endometrial cancer 086 080 093 interleukin18 lung cancer 087 081 093 betachemokinerantes ovarian cancer 070 057 085 positive associations monokine induced gamma interferon endometrial cancer 373 186 747 cutaneous tcell attracting chemokine lung cancer 151 122 187 associations similar sensitivity analyses supported colocalization analysesconclusionsour study adds current knowledge role specific inflammatory biomarker pathways cancer aetiology validation needed assess potential cytokines pharmacological lifestyle targets cancer prevention,0.0
incidence persistent lymphopenia people multiple sclerosis dimethylfumarate abstractbackground dimethyl fumarate dmf disease modifying therapy dmt used management multiple sclerosis ms lymphopenia occurs approximately 30 people receiving medication recently revised summary product characteristics spc recommends increased monitoring cessation medication context persistent lymphopenia increased risk progressive multifocal leukoencephalopathy pml therefore important clinicians patients aware frequency persistent moderatesevere lymphopenia order make informed decisions regarding drug choice safety monitoringmethods reviewed medical records 156 people ms pwms started dmf 20142020 received least 6 months treatment order identify incidence duration persistent lymphopeniaresult ten excluded due missing data 146 patients treated 307 months mean 16 11 found experience persistent moderate lymphopenia 0507109 l 5 3 experienced persistent severe lymphopenia 05109 l 5 patients persistent severe lymphopenia 3 discontinued dmf two cases stopped directly due spc recommendations 6months dmts initiated treatment withdrawn case due lack efficacy two cases remained dmf persistent severe lymphopenia predated spc revision mean times persistent moderate severe lymphopenia 106 months 255 months respectively increased age predictor persistent lymphopenia b0071 p0004 sex previous dmt,0.0
constitutes good home care people dementia investigation views home care service recipients providers background objective explore people receiving providing care consider good inhome care people living dementiamethodswe conducted 36 indepth interviews two focus groups key stakeholders australia first quarter 2018 participants included receiving care 4 people living dementia 15 family carers providing care 9 case managers 5 service managers 10 home care workers qualitative thematic analysis guided braun clarkes sixstep approachresultsconsensus reached across groups five themes considered important good inhome dementia care 1 home care workers understanding dementia impact 2 home care workers demonstrating personcentred care empathy care relationship client 3 good relationships communication care worker person dementia family carers 4 home care workers knowing positive practical strategies changed behaviours 5 effective workplace policies workforce culture results contributed codesign dementia specific training program home care workersconclusionsit crucial consider views opinions stakeholder group involved providing receiving dementia care home care workers inform workforce training education program design service design results can used inform empower home care providers policy related decision makers guide delivery improved home care servicestrial registrationactrn 12619000251123,0.0
physiotherapists perceived role managing anxiety patients relapsingremitting multiple sclerosis mixedmethods study background anxiety common people multiple sclerosis pwms higher relapsingremitting ms rrms communitybased samples anxiety can impact selfefficacy pain fatigue engagement physical activity treatment adherence influence rehabilitation process little known physiotherapists manage anxiety pwms challenges associated anxiety throughout rehabilitation process community outpatient settingsmethodsa mixedmethods design combining crosssectional survey semistructured interviews ukphysiotherapists used answer research question inform qualitative study crosssectional survey collected data physiotherapists working neurology understand impact management anxiety people ms pwms rehabilitation analysis used descriptive statistics findings formed interview guide semistructured interviews specialist physiotherapists explored barriers facilitators managing anxiety pwms community outpatient settings identified perceived physiotherapy training needs offered suggestions develop physiotherapy research practice themes derived inductivelyresultsthe survey suggested pwms present anxiety impact rehabilitation physiotherapy management practices physiotherapist skills training needs five semistructured interviews specialist physiotherapists expanded survey findings identified five main themes understanding ms journey modifying assessment treatment anxiety management toolbox lagging behind musculoskeletal physiotherapy gaining knowledge skillsconclusionphysiotherapists encounter anxiety pwms community outpatient rehabilitation perceive role managing presents facilitators included communication listening skills opportunities develop strong therapeutic relationships poor training support lack clinical guidelines limited research evidence considered barriers clinically relevant learning opportunities interprofessional working greater support clinical supervision recommended better develop physiotherapy practice,0.0
comparative proteomic profiling identifies reciprocal expression mitochondrial proteins white gray matter lesions multiple sclerosis brains front neurol 2021 dec 24 12779003 doi 103389 fneur2021779003 ecollection 2021abstractmultiple sclerosis ms chronic inflammatory demyelinating disease central nervous system ongoing demyelination remyelination failure major factors progressive neurological disability report employed comprehensive proteomic approach immunohistochemical validation gain insight pathobiological mechanisms may associated progressive phase ms isolated proteins myelinated regions demyelinated whitematter lesions wmls graymatter lesions gmls wellcharacterized progressive ms brain tissues subjected labelfree quantitative mass spectrometry using systembiology approach detected increased expression proteins belonging mitochondrial electron transport complexes oxidative phosphorylation pathway wmls intriguingly many proteins pathways opposite expression patterns downregulated gmls progressive ms brains comparison human mitocarta database mapped mitochondrial proteins mitochondrial subunits wmls gmls taken together provide evidence opposite expression mitochondrial proteins response demyelination white graymatter regions progressive ms brainpmid35002930 pmcpmc8740228 doi103389 fneur2021779003,1.0
acute varicellazoster virus meningitis multiple sclerosis patient treated fingolimod rev neurol paris 2022 jan 6s00353787 21 007670 doi 101016 jneurol202109009 online ahead printno abstractpmid35000791 doi101016 jneurol202109009,0.0
review mechanism application keishibukuryogan front nutr 2021 dec 24 8760918 doi 103389 fnut2021760918 ecollection 2021abstractthe concept blood stasis called y xi chinese oketsu japanese one unique pathophysiology traditional medicine originated china inherited korea japan concept related multiple aspects hemodynamic disorders brought quantitative qualitative changes theorizes quantitative changes blood stasis related peripheral circulatory insufficiency chronic qualitative changes blood stasis produce stagnant blood turns pathological product cause inflammation lead organic changes trauma induced hematomas considered quantitative change blood also form blood stasis basic medicine research keishibukuryogan kbg japanese name traditional japanese medicine kampo one common anti blood stasis prescriptions also known guizhifulingwan gfw chinese traditional chinese medicine tcm indicated initiation quantitative changes closely related loss redox balances endothelial function induced oxidative stress following qualitative changes related coagulopathy hyper viscosity antiplatelet aggregation lipid metabolism regulation systemic leptin level lipid metabolism inflammatory factor cyclooxygenase1 2 cox1 2 interleukin6 8 tumor necrosis factor macrophage infiltration hyperplasia tissue fibrosis sclerosis caused transforming growth factor1 fibronectin dysfunction regulated cell deaths apoptosis autophagy ferroptosis ovarian hormone imbalance clinically kbg often used diseases related obstetrics gynecology endocrine metabolism rheumatology dermatology review give overview mechanism current clinical application kbg summary basic clinical research discuss future perspectivepmid35004802 pmcpmc8740291 doi103389 fnut2021760918,0.0
case report clinical imaging characteristics patient antiflotillin autoantibodies neuromyelitis optica multiple sclerosis front immunol 2021 dec 23 12808420 doi 103389 fimmu2021808420 ecollection 2021abstractbackground demyelination diseases complex puzzles always straightforward diagnose multiple sclerosis neuromyelitis optica two frequently encountered numerous autoantibodies newly discovered recent years significantly aided clinical reasoning diagnosis differentiating demyelination disorders report case demyelination disease antiflotillin autoantibodies positive common past referencescase summary patient presented characteristic neuromyelitis optica symptoms remission relapse images exhibited characteristics neuromyelitis optica spectrum illness multiple sclerosisconclusion first case report describing clinical course imaging characteristics demyelination illness associated antiflotillin autoantibodies although far appears subtype multiple sclerosis still potential separate ms nmosdpmid35003138 pmcpmc8733162 doi103389 fimmu2021808420,1.0
physical mental health comorbidities among adults multiple sclerosis mayo clin proc innov qual outcomes 2021 dec 23 6 1 5568 doi 101016 jmayocpiqo202111004 ecollection 2022 febabstractobjective compare incidence adjusted hazard ratios common cardiometabolic diseases musculoskeletal disorders psychological morbidities among adults without multiple sclerosis ms patients methods beneficiaries included international classification diseases ninth revision clinical modification diagnostic code ms n9815 national private insurance claims database clinformatics data mart optuminsight adults without ms also included n1 474 232 control group incidence estimates common cardiometabolic diseases musculoskeletal disorders psychological morbidities compared 5 years continuous enrollment survival models used quantify unadjusted adjusted hazard ratios incident morbiditiesresults adults ms higher incidence common cardiometabolic disease 516 2663 5164 vs 364 328 690 904 227 musculoskeletal disorder 688 3411 4959 vs 475 512 422 1 077 737 psychological morbidity 494 3305 6691 vs 308 380 893 1 235 388 adults without ms differences clinically meaningful p001 fully adjusted survival models revealed adults ms greater risk hazard ratio hr 137 95 ci 132 143 hr 119 148 common cardiometabolic diseases hr 159 95 ci 153 164 hr 122 277 musculoskeletal disorders hr 157 95 ci 151 162 hr 120 251 one impulse control disorders psychological morbidityconclusion adults ms significantly higher risk development common cardiometabolic diseases musculoskeletal disorders psychological morbidities p001 adults without ms efforts needed facilitate development improved clinical screening algorithms early interventions reduce risk chronic physical mental disease onset progression higher risk populationpmid35005438 pmcpmc8715377 doi101016 jmayocpiqo202111004,0.0
management endothelial dysfunction systemic sclerosis current developing strategies front med lausanne 2021 dec 22 8788250 doi 103389 fmed2021788250 ecollection 2021abstractsystemic sclerosis ssc autoimmune disease marked dysregulation immune system tissue fibrosis dysfunction vasculature vascular damage remodeling inadequate endothelial repair hallmarks disease since early stages ssc damage apoptosis endothelial cells ecs can lead perivascular inflammation oxidative stress tissue hypoxia resulting multiple clinical manifestations raynauds phenomenon edematous puffy hands digital ulcers pulmonary artery hypertension erectile dysfunction scleroderma renal crisis heart involvement severely affect quality life survival understanding pathogenic aspects biomarkers reflect endothelial damage ssc essential guide therapeutic interventions treatment approaches described sscassociated vasculopathy include pharmacological options improve blood flow tissue perfusion recently cellular therapy enhance endothelial repair promote angiogenesis heal injuries minireview examines current knowledge cellular molecular aspects ssc vasculopathy well established developing therapeutic approaches improving vascular compartmentpmid35004754 pmcpmc8727451 doi103389 fmed2021788250,0.0
integrated lymphopenia analysis younger older patients multiple sclerosis treated cladribine tablets front immunol 2021 dec 24 12763433 doi 103389 fimmu2021763433 ecollection 2021abstractcladribine tablets cladt preferentially reduce b t lymphocyte levels aging associated decline immune function effect cladt lymphocyte levels may differ age post hoc analysis combined data phase 3 clarity clarity extension oraclems studies examine effect age 50 50 years lymphopenia following cladt 35 mg kg cladt35 cumulative dose 2 years treatment 96 weeks cladt35 placebo given weeks 1 5 year 1 treatment weeks 48 52 year 2 treatment start studies absolute lymphocyte count alc levels lymphocyte subsets examined 1564 patients age 50 placebo n566 cladt35 n813 age 50 placebo n75 cladt35 n110 age groups following cladt35 treatment nadir alc occurred week 9 8 weeks following start year 1 treatment week 55 7 weeks following start year 2 treatment 96week period cd19+ b lymphocytes nadir occurred week 9 year 1 week 52 year 2 cd4+ t lymphocytes nadir occurred week 16 year 1 age groups weeks 60 72 year 2 age 50 50 groups respectively nadir cd8+ t lymphocytes occurred week 16 year 1 week 72 year 2 age 50 group levels remained normal range nadir occurred week 9 year 1 week 96 year 2 age 50 group lymphocyte recovery began soon nadir following cladt35 treatment median levels reached normal range end treatment year age groups week 96 25 patients treated cladt35 reported 1 episode grade 3 lymphopenia gr3l rate certain infections numerically higher older versus younger patients experienced gr3l conclusion cladt35 similar effect alc lymphocyte subsets younger older patient groupspmid35003076 pmcpmc8740297 doi103389 fimmu2021763433,0.0
extracellular vesicles exosomes ectosomes play key roles pathology brain diseases mol biomed 2021 jun 20 2 1 18 doi 101186 s43556021000405abstractlast century neurons glial cells mostly believed play distinct functions relevant brain progressively however became clear neurons astrocytes microglia cooperate intensely release binding signaling factors direct surface binding generation release extracellular vesicles exosomes ectosomes called together vesicles abstract present review focused vesicles fundamental various brain diseases properties extraordinary specificity membrane governs fusion distinct target cells variable depending state specificity cells origin target result vesicle fusion discharge cargos cytoplasm target cells cargos composed critical molecules proteins various nature function nucleotides especially mirnas playing critical roles immune neurodegenerative diseases among immune diseases multiple sclerosis affected extensive dysregulation cotrafficking neural glial vesicles distinct mirnas inducing severe reducing effects vesicledependent differences progressive relapsingremitting forms disease relevant clinical developments alzheimers disease vesicles can affect brain changing generation inducing corelease effective proteins tau neurons astrocytes specific mirnas can delay longterm development disease upon traffic bloodbrainbarrier vesicles various origin reach fluids essential identification biomarkers important diagnostic therapeutic innovations critical future many brain patientspmid35006460 doi101186 s43556021000405,0.0
systematic review risk sarscov2 infection severity covid19 therapies approved treat multiple sclerosis neurol sci 2022 jan 10 doi 101007 s10072021058463 online ahead printabstractthere growing concern multiple sclerosis ms patients certain therapies may higher risk severe coronavirus disease 2019 covid19 conducted systematic literature review examine available data us therapies approved treat ms risk sarscov2 infection severe covid19 outcomes conducted searches pubmed embase covid19 database may 2 2021 retrieved articles describing clinical data therapies approved treat ms risk infection sarscov2 effects therapies clinical outcomes covid19 literature search identified total 411 articles 97 pubmed 227 embase 87 database excluding duplicates screening identified 15 articles interest identified additional article broader secondary weekly search pubmed thus ultimately reviewed 16 observational studies available data suggest ms patients treated anticd20 monoclonal antibodies may increased risk severe covid19 subject relevant limitations generally studies identify increased risk covid19 worsening therapies approved treat ms based observational data biological plausibility novelty drugevent association public health implications subpopulation potential impaired response covid19 vaccines safety signal merits monitoringpmid35006442 doi101007 s10072021058463,0.0
using mnemonic management multiple sclerosis j neurosci nurs 2022 feb 1 54 1 4851 doi 101097 jnn0000000000000626abstractbackground multiple sclerosis ms disease involving demyelination central nervous system medication management ms vital step preventing disease progression objective article presents healthcare providers aidemmoire form mnemonic assist medication management ms methods explored recent guidelines systematic reviews randomized controlled trials using pubmed medline cinahl analyze role efficacy pharmacotherapy relapse prevention ms conclusion crucial consider classifications ms pathophysiology determine medication produces best results proposed mnemonic can support clinicians recall ability assist identifying respective ms medicationpmid35007262 doi101097 jnn0000000000000626,1.0
pharmacology focus multiple sclerosis treatment abstract available,0.0
vascular dementia crosstalk complement coagulation systems front cardiovasc med 2021 dec 23 8803169 doi 103389 fcvm2021803169 ecollection 2021abstractvascular dementia vad neurocognitive disorder caused reduced blood flow brain tissue resulting infarction second common type dementia complement coagulation systems evolutionary host defence mechanisms activated acute tissue injury induce inflammation clot formation lysis recent studies revealed systems closely interlinked overactivation systems recognised play key role pathogenesis neurological disorders alzheimers disease multiple sclerosis however role vad yet extensively reviewed review aims bridge gap knowledge collating current understanding vad enable identification complement coagulation components involved pathogenesis disorder may effects amplified supressed crosstalk exploration mechanisms may unveil novel therapeutic targets biomarkers improve current treatment strategies vadpmid35004913 pmcpmc8733168 doi103389 fcvm2021803169,0.0
tyrosine kinase tec regulates effector th17 differentiation pathogenicity plasticity tcelldriven intestinal inflammation front immunol 2021 dec 21 12750466 doi 103389 fimmu2021750466 ecollection 2021abstractt helper th 17 cells key controlling infections mediated extracellular bacteria fungi also triggering autoimmune responses th17 cells comprise heterogeneous subsets pathogenic functions can cease secrete hallmark cytokine il17a even convert t helper lineages process known transdifferentiation relying plasticity pathogenicity plasticity tightly linked il23 signaling show protein tyrosine kinase tec highly induced th17 cells th17 differentiation enhanced low interleukin6 il6 concentrations absence tec correlates increased stat3 phosphorylation higher il23r expression therefore uncovered function tec il6 sensing via stat3 cd4+ t cells defining tec finetuning negative regulator th17 differentiation subsequently using il17a fate mapping mouse combined vivo adoptive transfer models demonstrated tec restrained effector th17 differentiation also pathogenicity plasticity tcell intrinsic manner data suggest tec regulates inflammatory th17driven immune responses directly impacting disease severity tcelldriven colitis model notably consistent vitro findings elevated levels il23 receptor il23r observed intestinal pre postconversion th17 cells isolated diseased tec mice subjected adoptive transfer colitis highlighting fundamental role tec restraining il23r expression likely via il6stat3 signaling axis taken together findings identify tec negative regulator th17 differentiation pathogenicity plasticity contributing mechanisms help t cells orchestrate optimal immune protection restrain immunopathologypmid35003062 pmcpmc8728872 doi103389 fimmu2021750466,0.0
analysis multifocal visual evoked potentials using artificial intelligence algorithms transl vis sci technol 2022 jan 3 11 1 10 doi 101167 tvst11110abstractpurpose clinical trials remyelination multiple sclerosis ms require imaging biomarker multifocal visual evoked potential mfvep accurate technique measuring axonal conduction however produces large datasets requiring lengthy analysis human experts detect measurable responses versus noisy traces study aimed develop machinelearning approach identification true responses versus noisy traces detection latency peaks measurable signalsmethods obtained 2240 mfvep traces 10 ms patients using vs1 mfvep machine classified skilled expert twice interval 1 week 2025 90 classified consistently used study resnet50 vgg16 models trained tested produce three outputs signal upsloped signal downsloped signal model ran 1000 iterations stochastic gradient descent optimizer learning rate 00001results resnet50 vgg16 falsepositive rates 17 06 respectively testing dataset analyzed n 612 falsenegative rates 82 65 respectively dataset latency measurements validation testing cohorts study similarconclusions models efficiently analyze mfveps 2 false positives compared human false positives 8translational relevance mfvep safe neurophysiological technique analyzed using artificial intelligence can serve efficient biomarker ms clinical trials signal latency measurementpmid35006263 doi101167 tvst11110,1.0
infectious risk multiple sclerosis patients treated diseasemodifying therapies threeyear observational cohort study mult scler j exp transl clin 2022 jan 4 8 1 20552173211065731 doi 101177 20552173211065731 ecollection 2022 janmarabstractbackground diseasemodifying therapies dmts largely used multiple sclerosis ms may result higher infectious riskobjective aimed investigate infectious risk dmttreated ms patientsmethods ms patients evaluated infectious risk starting switching dmtresults threeyear observational cohort study 174 ms patients enrolled among 18 patients antihbc + 19 patients quantiferontb gold intube qft + patients antihbc + showed detectable hbvdna started dmt among qtb + patients 17 latent tb infections ltbis 2 active tb infections tbis identified one month ltbi prophylaxis tb treatment respectively patients started dmtsoverall 149 started dmts dmts one ocrelizumabtreated patient antihbc + developed hbv reactivation six patients 3 natalizumab 2 ocrelizumab 1 ifn showed reactivation hsv1 detectable plasma dna finally 1 cladribinetreated patient experienced vzv reactivation reactivations latent infections successfully treatedconclusion screening infectious diseases dmt candidate ms patients helps mitigate infectious risk dmts regular assessment infectious risk allows avoid discontinuing ms therapy guarantees higher degree safetypmid35003758 pmcpmc8733376 doi101177 20552173211065731,0.0
improving health people multiple sclerosis multicenter randomized controlled study parallel groups preliminary results efficacy mindfulness intervention intention implementation associated physical activity program front psychol 2021 dec 24 12767784 doi 103389 fpsyg2021767784 ecollection 2021abstractobjectives objective study investigate efficacy psychological interventions mindfulness implementation intention associated physical activity program delivered via internet reducing multiple sclerosis symptoms method thirtyfive adults randomly assigned one three groups mindfulnessbased intervention group n 12 implementation intention group n 11 control group n 12 groups received physical activity program mindfulness condition group received daily training form prerecorded sessions implementation group elaborated specific plans week mobility fatigue impact disease patients life measured two measurement times carried prepost intervention baseline eight weeks results overall 8 weeks intervention results show significant increase walking distance three groups addition withingroup analysis showed statistically significant improvement pre post intervention physical component disease impact scale implementation intention group p 0023 large effect size mindfulnessbased intervention group p 0008 medium effect size control group p 0028 small effect size implementation intention group physical psychosocial cognitive fatigue impact subscales scores decreased significantly p 0022 p 0023 p 0012 respectively physical component statistically negatively correlated r 0745 p 0008 implementation intention group practice mild moderate physical activity mindfulnessbased intervention group physical component mfis showed statistically significant improvement p 0028 correlation moderatetovigorous physical activity mvpa control group outcomes reveal significant change conclusion results study encouraging show feasibility mindfulness interventions associated physical activity improve health people ms study assess mindfulness interventions tailored ms condition using hedonic eudemonic measures happinesspmid35002857 pmcpmc8740326 doi103389 fpsyg2021767784,0.0
ifnbeta causing focal segmental glomerulosclerosis multiple sclerosis patienta case report j ther 2021 jun 17 doi 101097 mjt0000000000001407 online ahead printno abstractpmid35006656 doi101097 mjt0000000000001407,0.0
response quot frailty multiple sclerosis closer look deficit accumulation frameworkquot mult scler 2022 jan 813524585211068150 doi 101177 13524585211068150 online ahead printno abstractpmid35000469 doi101177 13524585211068150,0.0
infections scleroderma digital ulcers single center cohort retrospective study dermatol reports 2021 oct 5 13 3 9075 doi 104081 dr20219075 ecollection 2021 nov 17abstractsystemic sclerosis ssc complex autoimmune 50 patients develop digital ulcers revised fifty consecutive patients sscrelated digital ulcers dus referred scleroderma unit thirtyfive showed clear signs dus infection underwent cutaneous swab microbiological data collection performed 87 cutaneous swabs overall dus recurrent 58 patients multiple 60 patients fourtyfour swabs 53 positive staphylococcus aureus 13 methicillinresistant 9 10 positive pseudomonas aeruginosa others less frequently isolated nine patients 25 needed hospitalization data support patienttailored approached dus particularly infected selfhygiene asepsis dressing procedures mandatory patient must trained avoid dangerous behaviors reduce risk infectionpmid35003566 pmcpmc8672119 doi104081 dr20219075,0.0
rituximab intravenous immunoglobulin treatment pm#x2f scl antibodyassociated disease casebased review rheumatol int 2022 jan 10 doi 101007 s0029602105075z online ahead printabstractautoantibodies 75kda 100kda subunits pm scl nucleolar protein complex associated overlap syndrome manifesting clinical features systemic sclerosis idiopathic inflammatory myopathy describe diverse clinical features series 4 cases antipm scl75 antipm scl100 antibodies including severe proximal muscle weakness oesophageal dysfunction respiratory weakness requiring mechanical ventilation raynauds calcinosis cutis sclerodactyly critical digital ischaemia despite severity striated oesophageal muscle weakness patients responded well immune suppression calcinosis cutis one case regressed substantially highlight efficacy rituximab intravenous immunoglobulin therapy ivig cases enabling return normal muscle function within six months rituximab preferentially chosen cases hypergammaglobulinemia multiple autoantibodies addition antipm scl ivig utilised cases rapid onset effect required severe ventilatordependent respiratory muscle weakness oesophageal dysfunctionpmid35006287 doi101007 s0029602105075z,0.0
editorial nuclear receptors coregulators metabolism immunity front endocrinol lausanne 2021 dec 24 12828635 doi 103389 fendo2021828635 ecollection 2021no abstractpmid35002987 pmcpmc8740238 doi103389 fendo2021828635,0.0
rho gtpase signaling rheumatic diseases iscience 2021 dec 14 25 1 103620 doi 101016 jisci2021103620 ecollection 2022 jan 21abstractrho guanosine triphosphatase gtpases molecular switches identified dysregulated involved pathogenesis various rheumatic diseases mainly including rheumatoid arthritis osteoarthritis systemic sclerosis systemic lupus erythematosus downstream pathways involving multiple types cells fibroblasts chondrocytes synoviocytes immunocytes mediated activated rho gtpases promote pathogenesis targeted therapy via inhibitors rho gtpases implicated treatment rheumatic diseases demonstrating promising effects review effects rho gtpases pathogenesis rheumatic diseases summarized rho gtpasemediated pathways elucidated therapeutic strategies using rho gtpase inhibitors rheumatic diseases also discussed provide insights exploration targeted therapy preclinical studies clinical practice future directions studies rho gtpases rheumatic diseases based current understandings providedpmid35005558 pmcpmc8718819 doi101016 jisci2021103620,0.0
guanidinoacetatecreatine secondary progressive multiple sclerosis case report j int med res 2022 jan 50 1 3000605211073305 doi 101177 03000605211073305abstractacute secondary progressive multiple sclerosis spms characterized escalating neurological disability limited diseasemodifying therapeutic options 48yearold woman acute spms treated interferon beta1a oral corticosteroids presented clinical outpatient diseasemodifying effects treatment decision made treat combination guanidinoacetate creatine 21 days made clinical progress followup intensity fatigue dropping severe mild magnetic resonance spectroscopy revealed increased brain choline creatine nacetylaspartate glutathione patients spms may benefit guanidinoacetatecreatine treatment terms patient clinicianreported outcomes requires additional studypmid35000485 doi101177 03000605211073305,0.0
il2 il2 receptor pathway key understanding multiple sclerosis j transl autoimmun 2021 sep 21 4100123 doi 101016 jjtauto2021100123 ecollection 2021abstractthe development progression diagnosis treatment autoimmune diseases multiple sclerosis ms convoluted processes remain incompletely understood multiple studies demonstrated interleukin il 2 il2 receptor il2r pathway plays pivotal role within processes striking functions il2 il2r pathway differential induction autoimmune responses tolerance paradoxical function il2 il2r pathway may attractive therapeutic target autoimmune diseases ms however exact mechanisms lead autoimmunity tolerance remain elucidated furthermore another factor pathway soluble form il2r sil2r complicates understanding role il2 il2r pathway ms challenge unravel mechanisms prevent diagnose recover ms review first current knowledge ms il2 il2r pathway summarized second key findings relation il2 il2r pathway ms highlighted eventually review may launch broad interest il2 il2r pathway propelling research autoimmune diseases including mspmid35005590 pmcpmc8716671 doi101016 jjtauto2021100123,0.0
threedimensional virtual histology cerebral cortex based phasecontrast xray tomography biomed opt express 2021 nov 15 12 12 75827598 doi 101364 boe434885 ecollection 2021 dec 1abstractin work optimize setups experimental parameters xray phasecontrast computedtomography threedimensional imaging cyto myeloarchitecture cerebral cortex including human murine tissue present examples different optical configurations using stateofthe art synchrotron instruments holographic tomography well compact laboratory setups phasecontrast tomography direct contrast edgeenhancement regime apart unstained paraffinembedded tissue tested hydrated tissue well heavy metal stained resinembedded tissue using two different protocols show image quality achieved allows assess neuropathology multiple sclerosis biopsy sample collected surgerypmid35003854 pmcpmc8713656 doi101364 boe434885,0.0
p037effect ozanimod treatment discontinuation absolute lymphocyte count moderatetosevere ulcerative colitis results phase 3 trial j gastroenterol 2021 dec 1 116 suppl 1 s9 doi 1014309 01ajg0000798748091383fabstractbackground ozanimod oral sphingosine 1phosphate s1p receptor modulator selectively targeting s1p1 s1p5 reduces migration lymphocytes involved adaptive immunity lymphoid tissues blood inflamed tissues preserving components innate immune response ozanimod approved multiple countries treatment relapsing forms multiple sclerosis us treatment moderatelytoseverely active ulcerative colitis uc reduction circulating lymphocytes expected based mechanism action ozanimod thought important driver efficacymethods assessed absolute lymphocyte count alc ozanimod induction maintenance ozanimod discontinuation per protocol adults moderatelytoseverely active uc characterize time course alc reduction recovery analysis included patients received ozanimod 092 mg equivalent ozanimod hcl 1 mg placebo daily true north phase 3 randomized trial nct02435992 10week induction period patients randomized 21 doubleblind treatment ozanimod placebo cohort 1 received openlabel ozanimod cohort 2 patients either cohort clinical response ozanimod week 10 rerandomized 11 doubleblind treatment ozanimod placebo maintenance week 52 placebotreated patients clinical response week 10 continued placebo maintenance alc assessed baseline visits throughout induction maintenanceresults total 69 patients received continuous placebo treatment 230 received continuous ozanimod treatment 227 received ozanimod induction placebo maintenance patients received continuous placebo mean alc remained stable 1821 x 109 l time normal range 102336 x 109 l ozanimodtreated patients mean alc reduced 4345 baseline 7073 patients alc shifts normal baseline low 9 l week 10 patients continued ozanimod mean alc reductions sustained approximately level alc shifts normal baseline low maintained 7389 patients maintenance patients received ozanimod induction therapy rerandomized placebo maintenance mean alc recovered within 8 weeks levels similar baseline induction proportion patients alc shifts normal baseline low decreased 73 week 10 6 week 52 fewer 2 ozanimodtreated patients alc 9 l either induction maintenance alc generally returned 02 x 109 l patients remained ozanimod among switched ozanimod induction placebo maintenance occurrences alc 9 l end maintenance patients serious opportunistic infection concurrent alc 9 lconclusion consistent mechanism action ozanimod alc reductions occurred ozanimod induction sustained maintenance incidence alc 9 l low alc recovered switching placebo patients require treatment discontinuation changes alcpmid35006165 doi1014309 01ajg0000798748091383f,0.0
intranasal administration fingolimod fty720 attenuates demyelination area lysolecithininduced demyelination model rat optic chiasm abstractbackground fingolimod fty720 oral immunosuppressive compound prescribed multiple sclerosis ms patients since 2010 lipophilicity low molecular weight fty720 allows cross blood brain barrier bbb exert peripheral central effects previous reports showed intranasal administration drugs preferred noninvasive route bypasses bbb improves delivery bioavailability central nervous system cns therefore aimed compare effects oral administrations fty720 astrocyte activation demyelination levels optic chiasm focal demyelination modelmethods experimental model induced injection 2 l lysolecithin 1 optic chiasm male wistar rats rats treated oral gavage intranasal drop fty720 dose 03 mg kg 14 days astrocyte activation analyzed using gfap immunostaining extent demyelination myelination levels measured fluoromyelin staining mog immunostaining respectively concentration fty720 measured high performance liquid chromatography hplc method brain tissuesresults data showed administration fty720 significantly decreases astrocyte activation demyelination levels optic chiasm compared oral administration route addition concentration fty720 higher brain tissue receiving rats compared oral treated groupconclusion seems administration fty720 may preferred route decline central inflammation demyelination levels ms patients,1.0
role interleukin17 signaling pathway interaction multiple sclerosis acute myocardial infarction abstractbackground correlational relationship well established multiple sclerosis acute myocardial infarction incidence however etiology underlying relationship remains unclear purpose study investigate mechanisms behind relationship identifying candidate genes interaction two diseasesmethods using computational biology approach existing gene expression data nih gene expression omnibus metaanalysis conducted six datasets evaluate upregulated downregulated genes shared diseases overlapping genes evaluated string find kegg biological pathway connecting genesresults metaanalysis found 78 overlap genes upregulation 65 downregulation genes displayed significant interaction string network plausible kegg pathway resulting string analysis interleukin17 signaling pathway seven genes metaanalysis s100a8 s100a9 cxcl8 cox2 ap1 ikba a20 involved pathwayconclusions il17 signaling pathway influences relationship multiple sclerosis acute myocardial infarction represents potential target drug intervention,0.0
mind wandering people multiple sclerosis psychometric study abstractbackground although mind wandering mw associated various psychological aspects frequently affected people multiple sclerosis pwms lack validated tools assess mw clinical populationobjectivethis psychometric study aimed assess structural construct validity reliability brief italian version mind wandering mw scale measures two different dimensions mw ie spontaneous mws deliberate mwd methodsstructural validity mw scale assessed explorative factor analysis efa investigate construct validity mood hospital anxiety depression scale personality 10items big five inventory test correlated mw constructs reliability assessed cronbachnulls internal consistency intraclass correlation coefficientsresultsefa confirmed two distinct constructs mw ie mws mwd also pwms tool appropriately fits graded response model supporting validity 79 hypotheses convergent discriminant constructs confirmed internal consistency mws cronbachnulls 84 mwd cronbachnulls 88 conclusionmw scale useful tool measure mw also pwms mw seems connected clinical manifestations ms detailed assessment mw encouraged clinical practice,0.0
comparison subjective objective measurements spasticity neuromyelitis optica spectrum disorder patients abstractbackgroundspasticity common disabling problem multiple sclerosis ms effect cns inflammatory demyelinating diseases cnsidds neuromyelitis optica spectrum disorder nmosd widely studied study aims compare subjective objective measurements spasticity nmosd patients determine associated factorsmethodsa prospective crosssectional study performed cnsidd patients attending multiple sclerosis related disorders clinic siriraj hospital tertiary hospital thailand june november 2020 performed ms nmosd myelin oligodendrocyte glycoprotein antibodyassociated disease mogad patients included patientsnull selfrated numeric rating scale nrs spasticity clinicianevaluated modified ashworth scale mas scores visit compared assessed correlations data characteristics patients including demographics number transverse myelitis tm attacks disease duration expanded disability status scale edss score collectedresultsseventynine cnsidd patients included 25 ms 53 nmosd 1 mogad statistically significant correlation nrs mas scores r0934 p 0001 spasticity commonly observed nmosd patients compared ms 34 vs 8 p0016 clinical characteristics strongly associated spasticity higher number tm attacks p 0001 severe tm attacks p 0001 longitudinally extensive transverse myelitis attacks p 0001 longer disease duration p0025 higher edss p 0001 pyramidal functional system scale scores p0001 conclusionspatientsnull selfreported nrs score good correlation clinicianevaluated mas score spasticity assessment nmosd cnsidd patients overall number severity tm attacks associated spasticity spastic patients disability measured edss,1.0
mapping european research networks providing health data results infact joint action healthinformation background research networks offer multidisciplinary expertise promote information exchange researchers across europe essential european unions eu health information system providers health information data aim mapping exercise identify analyze eu research networks terms health data collection methods quality assessment availability accessibility proceduresmethodsa webbased search performed identify eu research networks part international organizations eg whoeurope oecd involved collection data health monitoring health system performance assessment general characteristics research networks eg data sources representativeness quality assessment procedures availability accessibility health data collected ad hoc extraction formresultsfiftyseven research networks representative national international regional level identified networks data mainly collected administrative sources health surveys cohort studies 70 networks provide information quality assessment data collection procedures networks share macrodata articles reports microdata available ten networks request data access required 14 networks three apply financial charge networks share data research networks 8 49 specify metadatareporting standards used data description 9 49 conclusionsimproving health information availability high quality data priority europe research networks play major role tackling health data information inequalities enhancing quality availability accessibility health data data sharing across european networks,0.0
fingolimod impairs inactivated vaccine coronavac induced antibody response sarscov2 spike protein persons multiple sclerosis abstractbackground impact diseasemodifying treatments humoral response induced inactivated severe acute respiratory syndrome coronavirus 2 sarscov2 vaccines understudiedmethods recruited 34 persons multiple sclerosis ms fingolimod treatment 25 healthy individuals antisarscov2 spike igg indices measured elisa sera participants coronavac vaccinationsresults persons ms displayed significantly lower antibody levels seropositivity prevalence persons ms longer fingolimod treatment durations displayed lower antisarscov2 indicesconclusion results support previous findings regarding humoral response impairing effect fingolimod vaccinations patients fingolimod treatment may require closer monitoring covid19,0.0
pathological synuclein recruits lrrk2 expressing proinflammatory monocytes brain background leucine rich repeat kinase 2 lrrk2 snca genetically linked lateonset parkinsons disease pd aggregated synuclein pathologically defines pd recent studies identified elevated lrrk2 expression proinflammatory cd16+ monocytes idiopathic pd well increased phosphorylation lrrk2 kinase substrate rab10 monocytes lrrk2 mutation carriers brainengrafting proinflammatory monocytes implicated dopaminergic neurodegeneration pd models examine synuclein lrrk2 interact monocytes subsequent neuroinflammatory responsesmethodshuman mouse monocytes differentiated distinct transcriptional states resembling macrophages dendritic cells microglia exposed wellcharacterized human mouse synuclein fibrils lrrk2 expression lrrk2dependent rab10 phosphorylation measured monoclonal antibodies myeloid cell responses synuclein fibrils r1441clrrk2 knockin mice g2019slrrk2 bac mice evaluated flow cytometry chemotaxis assays performed monocytederived macrophages stimulated synuclein fibrils microglia boyden chambersresultssynuclein fibrils robustly stimulate lrrk2 rab10 phosphorylation human mouse macrophages dendriticlike cells cells synuclein fibrils stimulate lrrk2 jakstat activation intrinsic lrrk2 kinase activity feedforward pathway upregulates phosphorylated rab10 contrast lrrk2 expression rab10 phosphorylation suppressed microglialike cells otherwise highly responsive synuclein fibrils corroborating results lrrk2 expression brain parenchyma occurs proinflammatory monocytes infiltrating periphery distinct brainresident microglia mice expressing pathogenic lrrk2 mutations g2019s r1441c increased numbers infiltrating proinflammatory monocytes acute response synuclein fibrils primary cultured macrophages lrrk2 kinase inhibition dampens synuclein fibril microgliastimulated chemotaxisconclusionspathologic synuclein activates lrrk2 expression kinase activity monocytes induces recruitment brain results predict lrrk2 kinase inhibition may attenuate damaging proinflammatory monocyte responses brain,0.0
wilcoxonmannwhitney odds ratio statistical measure ordinal outcomes edss abstractbackground many clinical situations ordinal scales afford primary method semiquantifying patient outcomes field multiple sclerosis primary ordinal scale expanded disability status scale predominant methods ordinal scale statistical analysis provide pvalue without effect size rely heavily assumption proportionality odds subjecting lack power error wilcoxonmannywhitney odds statistical method provides significant information pvalue effect size number needed treat confidence intervals largely assumptionfree however utility demonstrated field multiple sclerosismethods three clinical studies field multiple sclerosis selected utilized ordinal scale outcomes group individual levels data studies extracted using webplotdigitizer custom wilxoconmannwhitney odds software applied dataset reanalyze main outcomes studiesresults reanalysis manuscript muraro et al 2017 demonstrated autologous stem cell transplantation relapsing remitting multiple sclerosis resulted 65 chance improving expanded disability status scale category although significant reanalysis manuscript songthammawat et al 2019 demonstrated chance improvement intravenous methylprednisolone concurrent plasma exchange 185 versus 32 intravenous methylprednisolone addon plasma exchange although significant reanalysis kister et al 2012 demonstrated chances mobility cognition scores generally favored decline every 5year increment study although statistically significant smaller effect sizes ranging 11 chance improvement 66 chance decline 5year intervaldiscussion wilcoxonmannwhitney odds simplifies ordinal data analysis robust largely assumptionfree nature place numerous statistical tests single test provides effect size estimate number needed treat pvalues confidence intervals importantly wilcoxonmannwhitney odds effect size calculation intuitively applicable individual populationlevels wilcoxonmannwhitney odds allows intuitive description progression large cohorts time able clearly convey odds mobility cognitive decline 30 years large multiple sclerosis cohort overall wilcoxonmannwhitney odds powerful robust statistical test significant promise within field multiple sclerosis,0.0
pediatric quality life multidimensional fatigue scale pedsqlmfs detects effects 3week inpatient body weight reduction program children adolescents obesity background fatigue frequent complaint amongst children adolescents obesity interferes adherence dietary exercise regimes reduce obesity present study evaluated effect inpatient 3week body weight reduction program body weight fatigue methodone hundred children adolescents obesity 64 female aged 1118 years undertook inpatient program personalized diet daily exercise education counsellingresultsthe sample evidenced mean reduction body mass females m 43 sd 21 kg p 001 males m 62 sd 26 kg p 001 bmi standard deviation score females m 017 sd 007 males m 024 sd 008 p 001 fatigue females m 78 sd 97 males m 50 sd 69 p 001 measured pediatric quality life multidimensional fatigue scale pedsqlmfs improvements attention problems subscale youth self report total sample m 089 sd 244 p 001 reliable change analyses revealed fatigue changes achieved 34 females 17 males majority achieve reliable change changes fatigue correlated changes body massconclusionsthe program achieved clinically significant improvements children adolescents future studies explore predictors treatment responsivenesstrial registration observational study registered,0.0
approval rates corneal donation origin donor tissue transplantation universitybased tertiary referral center corneal subspecialization hosting lions eye bank background increasing demand corneas eye banks must optimize tissue donation collection selection process retrospective monocentric study analyzed approval rates corneal donation origin reasons discarding donor corneas 2010 2019methodsdata included number deceased approval rejection family corneal donation contraindications corneal grafts included deceased persons fullbody multiorgan donors saarland university medical center uks external institutions additional analyzed parameters included endothelial cell count ecc blood sample serology infections conjunctival swab testing resultsa total 1748 corneoscleral buttons harvested 10 265 deceased persons 17 contraindication uks 2010 2019 consent rate 233 number explants increased 136 2010 15 deceased total 925 251 2019 21 total 1214 general departmentspecific data showed similar percentages corneal donation years intensive care palliative units recently providing corneas increase number corneas processed cornea bank years 368 2010 compared 857 2019 linked better internal supply 2010 262 712 total compared 2019 519 606 external supply reinforcement cooperation external hospitals including luxembourg 2010 106 288 total compared 2019 338 394 total 195 377 corneas 52 discarded 2009 compared 260 715 36 2019 main reasons discarding low ecc 36 discarded corneas 2009 11 2019 positive conjunctival swab 11 2009 13 2019 blood sample serology 6 2009 2019 conclusiondespite increasing number donors demand corneas still rising improved cooperation internal departments external clinics led increasing number explanted corneas main reason discarding corneas low ecc followed positive conjunctival swab fungal bacterial contamination serology increased donation rates continued improvements collection selection processes necessary cover high demand corneas,0.0
oct retinal nerve fiber layer thickness differentiates acute optic neuritis mog antibodyassociated disease multiple sclerosis rnfl thickening acute optic neuritis mogad vs ms abstractbackgroundoptic neuritis common manifestation myelin oligodendrocyte glycoprotein antibody associated disorder mogad multiple sclerosis ms acute mogad thought associated severe optic disc edema demyelinating diseases quantitatively confirmed goal study determine whether optical coherence tomography oct can distinguish acute optic neuritis myelin oligodendrocyte glycoprotein antibodyassociated disease mogad multiple sclerosis ms establish sensitivity oct confirmatory biomarker entitiesmethodsthis multicenter crosssectional study mogad ms patients peripapillary retinal nerve fiber layer prnfl thickness measured oct within two weeks acute symptom cirrus hdoct carl zeiss meditec inc dublin ca usa used measure prnfl acute eyes prior optic neuritis disc pallor excluded receiver operating characteristic roc curve analysis performed assess ability prnfl thickness distinguish mogad msresultssixtyfour mogad 50 ms patients met study inclusion criteria median age 465 years interquartile range iqr 343570 mogad group 304 years iqr 257384 ms group p0001 thirtynine 61 mogad patients female compared 42 84 ms p0007 median prnfl thickness 164m iqr 116212 96 acute mogad eyes compared 103m iqr 93113 51 acute ms eyes p0001 roc area curve prnfl thickness 081 95 confidence interval 074088 discriminate mogad ms prnfl cutoff maximized youdennulls index 118m provided sensitivity 74 specificity 82 mogad among 31 mogad 48 ms eyes unaffected contralateral eye prior baseline symptomatic eye median estimated prnfl thickening 45m iqr 17105 75m iqr 118 respectively p0001 mogad affected eyes 5m prnfl thickening whereas 26 54 ms affected eyes 5m thickeningconclusionoctderived prnfl thickness acute can help differentiate mogad ms can aid early diagnosis guide diseasespecific therapy acute setting antibody testing returns help differentiate borderline cases addition prnfl thickening sensitive biomarker confirming acute mogad clinically helpful used adjudication attacks future mogad clinical trials,1.0
protective effects melatonin changes occurring experimental autoimmune encephalomyelitis model multiple sclerosis abstractbackgroundmelatonin related pathophysiology multiple sclerosis ms antiinflammatory immunomodulatory properties proved numerous neurodegenerative diseases study aimed find whether melatonin supplement ms able act benefit clinical status ie oxidative stress inflammation indirect biomarkers bacterial dysbiosis lipopolysaccharide lps lpsbinding protein lbp verifying therapeutic potential possible clinical use patients msmethodsthe animal ms model experimental autoimmune encephalomyelitis eae employed whereby 25 male dark agouti rats 5 animals per group divided control group manipulated control+vehicle group control+melatonin group eae group eae+melatonin group melatonin administered daily 51 days dose 1mg kg body weight ip day five days weekresultsthe results administration melatonin demonstrated improvement clinical status diminution oxidative stress inflammation well bacterial dysbiosisconclusionmelatonin play effective role ms either alone therapy combined traditional agents,0.0
heimannbielschowsky phenomenon optic neuritis abstracta 32yearold woman relapsingremitting multiple sclerosis right optic neuritis incomplete remission presented unique neuroophthalmologic abnormality consisting spontaneous pendular vertical movement right eye consistent heimannbielschowsky phenomenon hbp rare form dissociated nystagmus probably reflects dual abnormality mechanism comprising coexistence asymmetric conduction delay optic nerve strategic network disruption brainstem gaze holding centres clinician important recognize rare neuroophthalmologic syndrome aware benign nature,0.0
systemic sclerosis complicated renal thrombotic microangiopathy case report literature review background systemic sclerosis ssc may overlap connective tissue diseases named overlap syndrome scleroderma renal crisis src rare severe complication ssc ssc related thrombotic microangiopathy ssctma infrequent pathology type src ssctma accompanied overlap syndrome rarecase presentationthis study reported case acute kidney injury aki accompanied overlap syndrome ssc systemic lupus erythematosus sle polymyositis pm renal pathology supported diagnosis ssctma sle pmrelated renal injury characterized renal arteriolar thrombosis endothelial cells edema little cast tubules mild immune complex deposition primary tma related factors adamts13 complement h factor normal thus case diagnosed secondary tma associated ssc patient treated renin angiotensin system inhibitors sildenafil supportive plasma exchange dialysis rituximab combined glucocorticoids 2 months peritoneal dialysis treatment renal function recovered dialysis stoppedconclusionthis study presented case ssctma overlap syndrome rituximab can used treatment option patients high src risk already manifesting src,0.0
edaravone activates gdnf#x2f ret neurotrophic signaling pathway protects mrnainduced motor neurons ips cells background spinal cord motor neurons mns human ips cells ipscs wide applications disease modeling therapeutic development amyotrophic lateral sclerosis als mnassociated neurodegenerative diseases need highly efficient mn differentiation strategies generating ipscderived disease models closely recapitulate genetic phenotypic complexity als important application models understand molecular mechanisms action fdaapproved als drugs show modest clinical efficacy novel mechanistic insights will help us design optimal therapeutic strategies together predictive biomarkers achieve better efficacymethodswe induce efficient mn differentiation ipscs 4 days using synthetic mrnas coding two transcription factors ngn2 olig2 phosphosite modification mns extensive characterization applied electrophysiological neurotoxicity assays well transcriptomic analysis study neuroprotective effect molecular mechanisms edaravone fdaapproved drug als improving clinical efficacyresultswe generate highly pure functional mrnainduced mns mimns control als ipscs well embryonic stem cells edaravone alleviates h2o2induced neurotoxicity electrophysiological dysfunction mimns demonstrating neuroprotective effect also found glutamateinduced mimn neurotoxicity model guided transcriptomic analysis show previously unrecognized effect edaravone induce gdnf receptor ret gdnf ret neurotrophic signaling vitro vivo suggesting clinically translatable strategy activate key neuroprotective signaling notably edaravone can replace required neurotrophic factors bdnf gdnf support longterm mimn survival maturation supporting neurotrophic function edaravoneactivated signaling furthermore show edaravone gdnf combined treatment effectively protects mimns h2o2induced neurotoxicity single treatment suggesting potential combination strategy als treatmentconclusionsthis study provides methodology facilitate ipsc differentiation disease modeling discoveries will facilitate development optimal edaravonebased therapies als potentially neurodegenerative diseasesgraphical abstract,1.0
experienced fatigue people rare disorders scoping review characteristics existing research background experienced fatigue underrecognized underresearched feature persons many different rare diseases better overview characteristics existing research experienced fatigue children adults rare diseases needed purpose review map describe characteristics existing research experienced fatigue selection rare diseases rare developmental defects anomalies embryogenesis rare genetic diseases furthermore identify research gaps point research agendasmethodswe applied scoping review methodology performed systematic search march 2020 bibliographic databases references sorted evaluated inclusion using endnote rayyan data extracted main research questions concerning characteristics research experienced fatigue definition focus fatigue study populations research questions investigated methods used resultsthis review included 215 articles ten different rare developmental defects anomalies embryogenesis 35 rare genetic diseases 215 articles 82 investigation experienced fatigue primary aim outcome included 9 secondary research articles reviews 206 primary research articles minority articles included children large differences number studies different diseases 29 215 articles gave description defined concept experienced fatigue common researchquestion reported prevalence associations fatigue least common diagnostics development validation fatigue assessment methods specific patient group large variety methods used investigate experienced fatigue impeding comparisons within across diagnosesconclusionthis scoping review characteristics fatigue research rare diseases found large variety research experienced fatigue however minority studies investigation experienced fatigue primary aim large variation experienced fatigue defined also measured within across diagnoses research experienced fatigue needed children adults rare diseases review offers basis research,0.0
abnormal activation yap#x2f taz contributes pathogenesis tuberous sclerosis complex hum mol genet 2022 jan 6ddab374 doi 101093 hmg ddab374 online ahead printabstractthe multisystemic genetic disorder tuberous sclerosis complex tsc impacts multiple neurodevelopmental processes including neuronal morphogenesis neuronal migration myelination gliogenesis alterations contribute development cerebral cortex abnormalities malformations although tsc caused mtorc1 hyperactivation cognitive behavioral impairments improved mtorc1 targeting making study downstream effectors complex important understanding mechanisms underlying tsc mtorc1 shown promote activity transcriptional coactivator yap hypothesized altered yap taz signaling contributes pathogenesis tsc first observed level yap taz increased human cortical tuber sample embryonic cortices tsc2 conditional knockout cko mice next determine abnormal upregulation yap taz impacts neuropathology tsc deleted yap taz tsc2 cko mice importantly yap taz tsc2 tcko animals show reduced cortical thickness cortical neuron cell size despite persistence high mtorc1 activity suggesting yap taz play downstream role cytomegaly furthermore yap taz tsc2 tcko significantly restored cortical hippocampal lamination defects reduced hippocampal heterotopia formation finally loss yap taz increased distribution myelin basic protein tsc2 cko animals consistent improvement myelination overall results indicate targeting yap taz lessens severity neuropathology tsc animal model study first implicate yap taz contributors cortical pathogenesis tsc therefore potential novel targets treatment disorderpmid34999833 doi101093 hmg ddab374,1.0
key players parthanatos opportunities targeting multiple levels therapy parthanatosbased pathogenesis cell mol life sci 2022 jan 9 79 1 60 doi 101007 s0001802104109wabstractparthanatos form regulated cell death involved pathogenesis many diseases particularly neurodegenerative disorders parkinsons disease alzheimers disease huntingtons disease amyotrophic lateral sclerosis parthanatos multistep cell death pathway cascade involves poly adpribose polymerase 1 parp1 overactivation par accumulation par binding apoptosisinducing factor aif aif release mitochondria nuclear translocation aif macrophage migration inhibitory factor mif complex mifmediated largescale dna fragmentation key players parthanatos pathway pleiotropic proteins diverse functions indepth understanding structurebased activity key factors biochemical mechanisms parthanatos crucial development drugs therapeutic strategies review delve key players parthanatos pathway reveal multiple levels therapeutic opportunities treating parthanatosbased pathogenesispmid35000037 doi101007 s0001802104109w,0.0
neurological update treatment escalation multiple sclerosis patients refractory fingolimodpotentials risks subsequent highly active agents j neurol 2022 jan 9 doi 101007 s00415021109561 online ahead printabstracta critical issue management relapsing ms rms discontinuation diseasemodifying treatments dmt due lack efficacy intolerability impending risks new therapeutic agents introduced treatment rms immediate longterm consequences sequential drug use well effect sequence drugs given unclear may affect efficacy adverse events longterm immunocompetence absence clinical studies specifically addressing concerns observations clinical practice particular value guiding current management algorithms prompted study published ferraro et al journal set provide overview published realworld evidence effectiveness safety switching fingolimod another dmt patients active rms seventeen publications reporting relevant information identified literature suggests immune cell depletion induced alemtuzumab ocrelizumab associated increased risk relapse worsening disability patients switching fingolimod compared patients switching therapeutic agents however evidence reported natalizumab cladribine inconclusive shortening washout period may limit early disease reactivation fingolimod discontinuation strong evidence duration washout period absolute lymphocyte count baseline predictors attenuated longterm efficacy realworld studies required better understand outcomes among patients underrepresented controlled trialspmid34999925 doi101007 s00415021109561,0.0
cerebellar contributions motor cognitive control multiple sclerosis arch phys med rehabil 2022 jan 5s00039993 21 017731 doi 101016 japmr202112010 online ahead printabstractobjective evaluate relationships specific cerebellar regions common clinical measures motor cognitive function persons multiple sclerosisdesign crosssectional setting laboratory participants twentynine pwms 28 age sexmatched healthy controlsinterventions applicable main outcome measures diffusion lobule mri analyses common clinical measures motor cognitive function used examine structurefunction relationships cerebellumresults pwms demonstrate significantly worse motor cognitive function compared controls weaker strength slower walking poorer performance symbol digit modalities test demonstrate differences cerebellar volume however pwms demonstrate significantly worse diffusivity mean diffusivity p00003 axial diffusivity p00015 radial diffusivity p00005 fractional anisotropy p0016 superior cerebellar peduncle scp primary output cerebellum increased volume motor lobules iv viii significantly related better motor p0022 cognitive p0046 performance increased volume cognitive lobules vivii also related better motor p0032 cognitive p0008 performance supporting role cerebellum motor cognitive functioningconclusion data highlight contributions cerebellum motor cognitive function pwms using novel neuroimaging techniques examine structurefunction relationships pwms improves understanding individualized differences heterogeneous group may provide avenue targeted individualized rehabilitation aimed improving cerebellar dysfunction mspmid34998712 doi101016 japmr202112010,0.0
hsv encephalitis associated offlabel rituximab treatment multiple sclerosis neurol sci 2022 jan 9 doi 101007 s10072021058030 online ahead printno abstractpmid35000014 doi101007 s10072021058030,0.0
hearing abnormalities multiple sclerosis clinical semiology pathophysiologic mechanisms j neurol 2022 jan 9 doi 101007 s0041502110915w online ahead printabstractauditory manifestations multiple sclerosis ms common wellrecognized sentinel exacerbations optic neuritis partial myelitis motor weakness vertiginous episodes heat intolerance eye movement abnormalities paper discusses four cases auditory changes secondary ms describes first case knowledge palinacousis perseveration hearing despite cessation sound stimulus characterize initial complaint diagnostic work ultimately underscore individualized treatment interventions allowed us achieve remission four cases individually codifying treatment regimens served mitigate abolish clinical derangements hearing special attention focused upon examination clinical manifestations pathophysiologic mechanisms responsible emphasize differential diagnostic considerations physical exam findings along results laboratory testing neuroimaging sequences lesion localization taken together information germane organizing cogently coherent strategic treatment plan s believe small case series represents clinically pragmatic example precision medicine principal theme goal throughout paper achievement ms also illustration assessment management schema neuroimmunologic disorders generalpmid34999960 doi101007 s0041502110915w,0.0
low vitamin d levels predict risk autoimmune disease following alemtuzumab treatment multiple sclerosis abstractalemtuzumab highly effective treatment multiple sclerosis ms treatment strategy two cycles 12 months apart lot appeal patients widespread use alemtuzumab tempered treatment emergent autoimmunity seen approximately onethird patients 5 years treatment postulated relative vitamin d deficiency may causative factor setting conducted retrospective casecontrol study looking association vitamin d potentially relevant clinical factors likelihood treatment emergent autoimmune disease following alemtuzumab occurrence autoimmunity monitored clinically bloodwatch monitoring program clinical data vitamin d levels obtained part routine clinical practice recorded vitamin d levels seasonally adjusted cases complete data included univariable multivariable cox proportional hazards analyses performed 113 patients treated alemtuzumab complete data median follow 44 years risk autoimmune disease associated lower vitamin d levels risk autoimmune disease associated female sex hr 35 higher edss score treatment association edss lost analysis restricted 4 years follow data support role vitamin d supplementation prevention autoimmune disease following alemtuzumab males lower risk autoimmunity following alemtuzumab,0.0
neutrophiltolymphocyte ratio monocytetolymphocyte ratio associated 2year relapse patients multiple sclerosis abstractbackgroundthe association increased neutrophiltolymphocyte ratio nlr multiple sclerosis demonstrated several studies monocytetolymphocyte ratio mlr emerging biomarker disease monitoring moreover published taiwanese study dateaimto investigate correlation nlr mlr white blood cell wbc count possible biomarkers predicting 2year relapse patients multiple sclerosis ms materials methodsa total 641 taiwanese patients ms enrolled present study january 1 2001 december 31 2018 collected data nlr mlr wbc count diseasemodifying therapy dmt use time first diagnosis first relapse patients within 2year durationresultsin relapse group significantly patients nlr median mlr median p0006 p0020 respectively also patients wbc count median although difference statically significant p0069 adjusted hazard ratio relapse nlr median 161 p0008 adjusted hazard ratio relapse mlr median 143 p0044 patients nlr median mlr median significantly p0008 p0039 respectively increased risk ms relapse 2 years compared nlr conclusionnlr mlr widely available fast measurable inflammatory markers predicting relapse risk ms patients,0.0
role inflammasomes vascular cognitive impairment abstractthere increasing prevalence vascular cognitive impairment vci worldwide several studies suggested chronic cerebral hypoperfusion cch plays critical role disease onset progression however limited understanding underlying pathophysiology vci especially relation cch neuroinflammation significant contributor progression vci increased systemic levels proinflammatory cytokine interleukin1 il1 extensively reported vci patients recently established cch can activate inflammasome signaling pathways involving nlrp3 aim2 inflammasomes critically regulate il1 production given neuroinflammation early event vci important understand molecular cellular mechanisms enable development diseasemodifying treatments reduce structural brain damage cognitive deficits observed clinically elderly hence review aims provide comprehensive insight molecular cellular mechanisms involved pathogenesis cchinduced inflammasome signaling vci,0.0
dmts trialed individuals ppms spms without recent disease activity yes multiple sclerosis ms poster child success neurology multiple discasemodifyingtherapies dmtss developed treat relapsing formsof ms unfortunately things bright forprogressive ms one approved dmtfor primary progressive pp ms ocrelizumabthere single modem crapositive phaseiii trialin secondary progressive sp ms siponimodmany dmtss approved food drugadministration fda active spms theydeclared form relapsing ms noclear benefit progressionprogressive ms results neurodegencerativeinjury widespread damage synapses axons neurons 3 clinical expression involves gradual onset neurologic deficits independent ofrelapses neurodegeneration present carliest disease time point ms yet clinicallymanifest midlife clinical expressionagelocked likely explanation acritical threshold exceeded due ms damage normal aging damage loss central nervoussystem cns reserve repair besimilar occurs alzheimer parkinsonsdisease also suggests clinical progression apparent almost late therapeuticexpectations must tempered best progressionmay slowed stopped cns repair strategies neededthe processes driving neurodegeneration themost part distinct driving focalinflammation include compartmentalizedpersistent cns inflammation oxidative injury tomitochondria axons neurotoxic glia withmarked microglial activation mechanisms suchas complementmediated axonal pruning ion channel redistribution axonal transport disruptions lossof trophic myelin factors loss cns repair andreserve abilities increased iron deposition andexcitotoxicity damaging mechanisms areenhanced aging selected comorbiditiesneurodegeneration considered processin progressive phenotypes supportedby molecular data well successful progressive trials combining patients ppms andspms evaluated highdose highgrade biotin ibudilast masitinibtreatment progressive ms now priority howdo optimize future clinical trials makerecruitment inclusive meaningful possible excluding active activeprogressive msproposed new treatments progressive ms shouldfocus unique pertinent damage mechanismsthey cnspenetrating agents termactive ms somewhat artificial refers occurrence clinical relapse formation macroscopic magnetic resonance mri lesion new enlarging t2 contrast lesion defined periodsuch last year clearly allornonephenomenon overlap occurs routinely about15 ppms will experience relapse annually andcontrast lesions seen 42 ppms early macroscopic lesions also well recognized everyspms patient starts relapsing patient notrelapsing one day progressive next day therelapsing spms transition period lasts leastsyearsshould active progressive ms excluded trialsof new agents treat neurodegencration must bestudied separate neurodegeneration trials diseaseactivity arbitrarily confined strict timeframeofl or2 years guarantee excludedfocal inflammation exclude neurodegeneration ms phenotype working group indicated patients stratified entry andanalyzed disease subtype tracked,1.0
geneenvironment interactions increase risk pediatriconset multiple sclerosis associated ozone pollution backgroundwe previously reported relationship air pollutants increased risk pediatriconset multiple sclerosis poms ozone air pollutant may play role multiple sclerosis ms pathoetiology cd86 nonhla gene associated poms expression antigenpresenting cells apcs changed response ozone exposureobjectivesto examine association countylevel ozone poms interactions ozone pollution cd86 hladrb115 strongest genetic variant associated pomsmethodscases controls enrolled environmental genetic risk factors pediatric ms study us network pediatric ms centers countylevelmodeled ozone data acquired cdcs environmental tracking network participants assigned ozone values based county residence values categorized tertiles based healthy controls association ozone tertiles ms assessed logistic regression interactions tertiles ozone level gg genotype rs928264 g single nucleotide polymorphism snp within cd86 presence drb11501 drb115 odds poms evaluated models adjusted age sex genetic ancestry mothers education additive interaction estimated using relative excess risk due interaction reri attributable proportions aps disease calculatedresultsa total 334 poms cases 565 controls contributed analyses countylevel ozone associated increased odds poms odds ratio 247 95 confidence interval ci 169359 195 95 ci 132288 upper two tertiles respectively compared lowest tertile significant additive interaction high ozone tertiles presence drb115 reri 221 95 ci 083359 ap 056 95 ci 033079 additive interaction high ozone tertiles cd86 gg genotype present reri 160 95 ci 014306 ap 037 95 ci 0001075 compared lowest ozone tertile ap results indicated approximately half poms risk subjects can attributed possible interaction higher countylevel ozone carrying either drb115 cd86 gg genotypeconclusionsin addition association high countylevel ozone poms report evidence additive interactions higher countylevel ozone drb115 cd86 gg genotype identifying geneenvironment interactions may provide mechanistic insight biological processes play ms susceptibility work suggests possible role apcs countylevel ozoneinduced poms risk,0.0
genes brain dynamics art genetic underpinnings creativity dancing musicality visual arts j integr neurosci 2021 dec 30 20 4 10951104 doi 1031083 jjin2004110abstractcreativity art artistic creation music dance visual arts brain activities specific humans genetic background remained unexplored years many recent studies uncovered significant associations cognitionrelated genes loci studies summarized present article creativity trait heavy genetic influences also associated mental disorders altruism associated genes include dopaminergic serotoninergic genes a1antitrypsin neuregulin brainderived neurotrophic factor music another complex phenotype important genetic background studies musicians families highlighted contribution loci eg 4q22 specific genes vasopressin receptor 1 serotonin transporter latter two also associated dancing although studies investigated visual arts appear influenced genetic differences explain increased prevalence synesthesia artists individuals autism lastly although genes play important role creativity art epigenetics environment overlooked genetic exploration artistic creativity may provide useful knowledge cognition behavior brain function may also enable targeted personalized art therapy health diseasepmid34997732 doi1031083 jjin2004110,0.0
effects transcranial direct current stimulation sleep patients multiple sclerosisa pilot study neurophysiol clin 2022 jan 4s09877053 21 001271 doi 101016 jneucli202112001 online ahead printabstractbackground sleep complaints commonly reported patients multiple sclerosis pwms several pharmacological alternative interventions tried usually faced limited efficacy hence exploring methods transcranial direct current stimulation tdcs might interest aim study assess effects bifrontal tdcs subjective ie epworth sleepiness scale ess objective sleep measures ie actigraphy methods seven patients completed study patients randomly received two blocks five daily sessions crossover design active sham washout interval three weeks anode cathode placed left right dorsolateral prefrontal cortices respectively sleep assessment included ess sleep onset latency total sleep duration time bed sleep efficiency waking sleep onset number awakeningsresults compared baseline scores 1114 406 significant decrease ess obtained active intervention 786 418 p 0011 sham intervention 957 562 p 0142 significant changes observed regards actigraphy measures sessions well tolerated serious sideeffects reported timeconclusion bifrontal tdcs resulted significant improvement daytime sleepiness yield effect objective sleep measures pwms discrepency might explained modest association exist objective subjective sleep measures addition assumed modulating objective sleep measures require larger sample size stimulation sessions modulation cortical areaspmid34996695 doi101016 jneucli202112001,0.0
dairy intake parkinson#39 s disease mendelian randomization study mov disord 2022 jan 8 doi 101002 mds28902 online ahead printabstractbackground previous prospective studies highlighted dairy intake risk factor parkinsons disease pd particularly men unclear whether association causal explained reverse causation confoundingobjective aim examine association genetically predicted dairy intake pd using twosample mendelian randomization mr methods genotyped wellestablished instrumental variable dairy intake located lactase gene rs4988235 within couragepd consortium 23 studies 9823 patients 8376 controls european ancestry results based dominant model association genetic predisposition toward higher dairy intake pd odds ratio per one serving per day 170 95 confidence interval 112260 p 0013 restricted men 250 137456 p 0003 pdifference women 0029 conclusions using mr findings provide support causal relationship dairy intake higher pd risk biased confounding reverse causation studies needed elucidate underlying mechanisms 2022 international parkinson movement disorder societypmid34997937 doi101002 mds28902,0.0
fty720 resistant human epidermal growth factor receptor 2positive breast cancer sci rep 2022 jan 7 12 1 241 doi 101038 s4159802104328yabstractthe prognosis patients human epidermal growth factor receptor 2 her2 positive breast cancer considerably improved however reliable treatment besides antiher2 strategies available fty720 smallmolecule compound used treating refractory multiple sclerosis reported beneficial effects cancers therefore evaluated efficacy fty720 trastuzumabresistant breast cancer cells investigated possible mechanism involved study evaluated morphological changes fty720 treatment antiproliferative wst1 assays ldh cytotoxicity assay kits used determine treatment effects drugs whereas western blot analysis used evaluate protein expression apoptotic events investigated annexin v staining tunel assays using flow cytometry fty720 effective trastuzumabresistant breast cancer cell lines despite presence pik3ca mutation studied xenograft mouse model fty720treated groups statistically significantly poorer hcc1954 xenograft growth vivo compared control group findings suggest fty720 can overcome resistance trastuzumab therapy patients her2positive breast cancer fty720 plus trastuzumab might offer even better efficacy vitro vivopmid34997132 doi101038 s4159802104328y,0.0
correction innovative approach modelling optimal treatment sequence patients relapsingremitting multiple sclerosis implementation validation impact decisionmaking approach adv ther 2022 jan 8 doi 101007 s1232502102032x online ahead printno abstractpmid34997918 doi101007 s1232502102032x,0.0
residual symptoms longterm outcomes allcause autoimmune encephalitis adults j neurol sci 2021 dec 31 434120124 doi 101016 jjns2021120124 online ahead printabstractbackground objectives evaluate residual symptoms allcause autoimmune encephalitis reallife outpatient setting compare longterm outcome measures secondary objective identify correlates poor outcomesmethods analyzed patients referred neuroimmunology clinic evaluation autoimmune encephalitis standardized data collected compared prevalence symptoms latest followup presentation calculated symptom improvement rates compared modified rankin scale mrs clinical assessment scale autoimmune encephalitis case nonparametric wilcoxon rank sum tests fishers exact tests used compare clinical attributes patients without poor outcomesresults evaluated 54 patients 2017 2021 33 met inclusion criteria average age 4720 years 57 females 55 seropositive latest followup 94 improved compared presentation six patients 18 poor outcomes defined mrs 3 common residual symptoms cognitive mood dysfunction highest improvement rates alertness psychosis lowest motor function ataxia case moderate correlation mrs r2 053 95ci023 074 p 00015 captured nuances mrs presentation followup older age higher posttreatment case score correlated poor outcomesdiscussion autoimmune encephalitis patients experience symptom improvement posttreatment case score representative wide symptomatic spectrum autoimmune encephalitis correlated poor outcomes however case capture patients dysautonomia sleep dysfunction deathpmid34998237 doi101016 jjns2021120124,0.0
optical coherence tomography angiography octa differential diagnosis aquaporin4 antibody seronegative nmosd multiple sclerosis abstractbackround optic neuritis common feature relapsingremitting multiple sclerosis rrms neuromyelitis optica spectrum disorders nmosd crucial early differentiate two diseases differ pathophysiology treatmentobjective compare nmosd rrms patients using optical coherence tomography oct oct angiography octa assess retinal microvascular network differencesmethods fourteen rrms 28 eyes 9 nmosd patients 18 eyes 11 controls enrolled seropositivity aquaporin4 antibody antiaqp4 abs 444 peripapillary macular retinal nerve fiber layer rnfl thickness superficial peripapillary macular vessel density vd area perimeter circularity foveal avascular zone faz analyzedresults octa showed reduction peripapillary macular vd faz size nmosd+on compared rrms+on controls p0001 p0001 p0010 p0001 respectively peripapillary vd similar rrms +on controls peripapillary vd monophasic seronegative nmosd+on eyes significantly lower monophasic rrms+on eyes p0030 different controls faz area smaller unaffected eyes nmosd rrms controlsconclusions oct octa revealed considerable differences rrms nmosd patients providing promising results favor clinical utility octa differential diagnosis particularly antiaqp4 antibody negative patients octa might useful biomarker differentiating nmosd ms,0.0
research progress application mesenchymal stem cells chronic inflammatory systemic diseases abstractchronic inflammatory systemic diseases result bodys immune imbalance long course recurring episodes immunosuppressants main treatment patients respond well capable selfrenewal differentiation multiple tissue cells low immunogenicity mesenchymal stem cell promising treatment chronic inflammatory systemic diseases article describe research progress clinical application mesenchymal stem cells chronic inflammatory systemic diseases look influencing factors biomarkers can predict outcome patient mesenchymal stem cell transplantation,0.0
hypogonadism men multiple sclerosis prevalence clinical associations summaryit hypothesized multiple sclerosis ms hormonal influences testosterone may antiinflammatory functions context given prior reports lower testosterone levels men ms archival serum samples evaluated prevalence hypogonadism clinical setting association disability men ms subjects screened symptoms hypogonadism using clinical instrument positive screens total free morning testosterone levels checked 64 subjects screened 50 78 positive results 46 92 morning testosterone levels checked among latter 5 found testosterone levels lower limit normal expected inverse relation bmi testosterone correlate demographic disease related factors baseline testosterone predict risk edss t25fw progression future mri activity,0.0
potential application cryobiopsy histomolecular characterization mediastinal lymph nodes patients thoracic malignancies case presentation series implications future developments background management nonsmall cell lung cancer nsclc become increasingly complex due evolution personalized medicine approaches approaches characterized necessity adequate tumor samples hence improved biopsy techniques needed transbronchial lung cryobiopsy novel endoscopic procedure designed collect peripheral pulmonary tissue currently employed interstitial lung diseases use technique oncology might result improved mediastinum staging molecular characterizations however available data involving use cryoprobe mediastinal lymph nodes still limitedcase presentationhere present series five consecutive patients underwent endoscopic assessment mediastinal lymph nodes oncologic reasons patients subjected endobronchial ultrasoundguided transbronchial needle aspiration ebus tbna cryobiopsy mediastinal lymph nodes procedure complications observed three reported cases cryobiopsy cell block ebus tbna positive one case cryobiopsy diagnostic ebus tbna negative moreover one case showed discordance procedures cryobiopsy negative cell block obtained multiple stations diagnostic small cell lung cancer one case involving patient treated lymphoma cryobiopsy provided complete histologic characterization another case involving patient affected nsclc cryobiopsy provided material molecular analysesconclusionthis case presentation series suggests cryobiopsy generally used peripheral lung lesions far feasible safe approach diagnosis staging mediastinal lymph nodal involvement especially station 7 involved compared ebus tbna cryobiopsy might provide adequate histological samples possible impact molecular characterizations therefore therapeutic decisions however learning curve procedure understated optimal protocols implementing technique needed opinion studies designed integrate routine use cryobiopsy current practice solid eventually hematologic tumors mediastinal lymph node involvement warranted,0.0
gastrointestinal pathologic findings teriflunomide associated diarrhea abstractbackgrounddiarrhea generally benign selflimited adverse effect teriflunomide small intestinal pathology yet described teriflunomide associated diarrheaobjectiveto report small intestinal pathology teriflunomide associated diarrheamethodssmall intestinal colonic biopsies obtained patient teriflunomide associated diarrhearesultssmall intestinal biopsy demonstrated blunting villi increased intraepithelial lymphocytes expansion lamina propria gliadin ttransglutaminase antibodies negative diarrhea resolved following elimination teriflunomide cholestyramineconclusionthis first reported case small intestinal inflammation similar celiac disease teriflunomide associated diarrhea,0.0
comparison sarscov2 antibody response two doses mrna inactivated vaccines multiple sclerosis patients treated diseasemodifying therapies abstractbackground diseasemodifying therapy weaken immune system decrease immune response vaccines essential know vaccine protective sarscov2 multiple sclerosis populationobjective assess immune response messenger rna bnt162b2 pfizer biontech inactivated sinovac vaccines people multiple sclerosis pwms treated diseasemodifying therapy dmt compared healthy controlsmethods singlecentre crosssectional study included 526 ms patients treated dmt 44 healthy controls 21 untreated patients ms may 2021 september 2021 serum samples collected least two weeks second dose vaccineresults participants vaccinated bnt162b2 higher antibody titer sinovac group 95ci1023 1473 p 001 significant difference antibody titer pwms without treatment hc found 95ci 882 935 p 99 65 adults without dmt use hc+pwmswithout treatment seronegative cases observed vaccine group patients treated dmt bnt162b2 associated 163 greater absolute risk seropositivity sinovacconclusion mrna vaccine preferred choice protection sarscov2 pms treated dmt,0.0
vcp#x2f p97 inhibitor cb5083 modulates muscle pathology mouse model vcp inclusion body myopathy background pathogenic gain function variants valosincontaining protein vcp cause unique disease characterized inclusion body myopathy earlyonset paget disease bone frontotemporal dementia also known multisystem proteinopathy msp previous studies drosophila models vcp disease indicate treatment vcp inhibitors mitigates disease pathology earliergeneration vcp inhibitors display offtarget effects relatively low therapeutic potency new generation vcp inhibitors needs evaluated mouse model vcp disease study tested safety efficacy novel potent vcp inhibitor cb5083 using vcp patientderived myoblast cells animal model vcp diseasemethodsfirst analyzed effect cb5083 patientderived myoblasts typical disease autophagy tdp43 profile western blot next determined maximum tolerated dosage cb5083 mice treated 2monthold vcpr155h r155h mice 5 months 15 mg kg cb5083 analyzed motor function monthly rotarod assessed endpoint blood toxicology muscle brain pathology including autophagy tdp43 profile using western blot immunohistochemistry also treated 12monthold vcpr155h + mice 6 months performed similar analysis finally assessed potential side effects cb5083 retinal function using electroretinography chronically treated vcpr155h 155h miceresultsin vitro analyses using patientderived myoblasts confirmed cb5083 can modulate expression proteins autophagy pathways found chronic cb5083 treatment well tolerated homozygous mice harboring patientspecific vcp variant r155h can ameliorate muscle pathology characteristic disease vcpassociated pathology biomarkers elevated tdp43 p62 levels significantly reduced finally address potential adverse effect cb5083 visual function observed previous oncology clinical trial analyzed retinal function mice treated moderate doses cb5083 5 months documented absence permanent ocular toxicityconclusionsaltogether findings suggest longterm use cb5083 moderate doses safe can improve vcp diseaseassociated muscle pathology results provide translationally relevant evidence vcp inhibitors beneficial treatment vcp disease,0.0
identification common susceptibility genes drug target genes multiple sclerosis systemic lupus erythematosus rheumatoid arthritis value guide clinical treatment abstractbackgroundmultiple sclerosis ms autoimmunemediated demyelinating disease white matter central nervous system cns clinical practice found ms associated variety autoimmune diseases systemic lupus erythematosus sle rheumatoid arthritis ra aim study identify common susceptibility genes drug target genes ms sle ra provide new insights treatmentmethodsthe common susceptibility genes ms sle ra obtained searching gwas database using microarray data validate genome ontology go kyoto encyclopedia genes genomes kegg analyses performed common kegg pathways selected genes enriched common pathways obtained intersected susceptibility genes ms sle ra obtain pathway genes respectively found common pathogenesisrelated genes three diseases reviewing literature drugbank database drugs drug target genes approved treatment three diseases obtained finally dgidb database searched predict potential drugs molecular compounds interact susceptibility genes common ms sle raresultsin ms sle ra 46 common susceptibility genes 23 significantly differentially expressed microarray expression profile 2117 genes obtained 42 common pathways among 17 pathogenesisrelated genes common ms sle ra drugbank database used obtain 29 drug target genes ms 43 drug target genes ra 20 drug target genes sle dhodh common drug target gene ms sle ra corresponding drugs leflunomide teriflunomide total 13 genes 366 potential drugs molecular compounds predicted interaction relationships searching dgidb databaseconclusionthe common susceptibility genes drug target genes among ms sle ra provide theoretical basis comorbidity phenomenon three diseases clinical practice may guide clinical treatment,1.0
esomeprazole alleviates fibrosis systemic sclerosis modulating ahr#x2f smad2#x2f 3 signaling pharmacol res 2022 jan 4106057 doi 101016 jphrs2022106057 online ahead printabstractsystemic sclerosis ssc connective tissue disease involvement complex signaling pathways tgf smad2 3 ssc can lead severe multiple organ fibrosis effective therapy currently available unclear pathogenesis exploring new treatments focus recent research ssc recent studies implied potential antifibrotic role esomeprazole eso currently unidentified mechanisms signaling ahr liganddependent transcription factor described key controller fibrosis tumorigenesis immune balance recently reported eso may exogenous agonist ahr signaling previous study revealed effects eso ssc underlying mechanisms study demonstrate eso suppresses migration ssc dermal fibroblasts downregulates profibrotic markers including colia1 sma ctgf mmp1 limits collagen production potentially via activation ahr signaling importantly eso block smad2 3 phosphorylation concurrently reduction collagen via ahr signaling moreover results bleomycin blm induced ssc model skin lung shows eso ameliorates fibrosis vivo keeping vitro results conclude eso potential therapeutic drug ssc fibrosispmid34995795 doi101016 jphrs2022106057,0.0
envisioning postpandemic digital neurological psychiatric mental health care front digit health 2021 dec 21 3803315 doi 103389 fdgth2021803315 ecollection 2021abstractthe sarscov2 pandemic placed dramatic burden managed healthcare perhaps nowhere evident neurological psychiatric disease care said duration pandemic mandated adaptability entire care system oftvaunted benefits telehealth telemedicine subjected deep scrutiny scale positive experiences reported patients providers routine checkups use cognitive behavioral therapy associated mental disorders management complex diseases multiple sclerosis neurological psychiatric conditions integration standard care looks likely post pandemic era many healthcare systems moving expand reimbursement categories develop equitable incentive models developers providers commentary share perspective future care may evolve hybrid delivery models advent new therapeutic approaches can address pain points identified pandemicpmid34993505 pmcpmc8724196 doi103389 fdgth2021803315,0.0
physical exercise therapy autoimmune neuroinflammation application knowledge animal models patient care autoimmun rev 2022 jan 4103033 doi 101016 jautrev2022103033 online ahead printabstractphysical exercise pe impacts various autoimmune diseases accordingly clinical trials demonstrated safety pe multiple sclerosis ms patients indicated beneficial outcomes also increasing body research beneficial effects exercise experimental autoimmune encephalomyelitis eae animal model ms various mechanisms underlying effects suggested however despite documented favorable impact pe health still lack thorough understanding effects autoimmune neuroinflammation specific guidelines pe therapy ms patients lacking end current findings impact pe autoimmune neuroinflammation human ms animal models reviewed concept personalized pe therapy autoimmune neuroinflammation discussed future research providing biological rationale clinical trials pave road precise pe therapy ms patients describedpmid34995760 doi101016 jautrev2022103033,0.0
stable multiple sclerosis patients anticd20 therapy go extended interval dosing mult scler 2022 jan 713524585211064441 doi 101177 13524585211064441 online ahead printno abstractpmid34994665 doi101177 13524585211064441,0.0
body mass index predictor ms activity progression among participants benefit mult scler 2022 jan 713524585211061861 doi 101177 13524585211061861 online ahead printabstractbackground lack studies association obesity conversion clinically isolated syndrome cis multiple sclerosis ms objective aim study determine whether obesity predicts disease activity prognosis patients cismethods body mass index bmi baseline available 464 patients cis benefit obesity defined bmi 30 kg m2 normal weight 185 bmi 25 patients followed 5 years clinically magnetic resonance imaging hazard conversion clinically definite cdms 2001 mcdonald criteria mdms ms annual rate relapse sustained progression expanded disability status scale edss change brain lesion volume development new brain lesions evaluatedresults obese individuals 39 likely convert mdms 95 ci 102191 p 004 59 95 ci 101231 p 003 higher rate relapse individuals normal weight associations observed obesity conversion cdms sustained progression edss magnetic resonance imaging mri outcomes except larger reduction brain volume obese smokers compared normal weight smokers 082 95 ci 151 012 p 002 conclusion obesity associated faster conversion ms mdms higher relapse ratepmid34994579 doi101177 13524585211061861,0.0
iron rims patients multiple sclerosis neurodegenerative marker 7tesla magnetic resonance study front neurol 2021 dec 21 12632749 doi 103389 fneur2021632749 ecollection 2021abstractintroduction multiple sclerosis ms demyelinating neurodegenerative disease central nervous system characterized inflammatorydriven demyelination symptoms ms manifest physical neuropsychological deficits time inflammation accompanied neurodegeneration indicated brain volume loss mri combined clinical imaging serum biomarkers patients iron rim lesions irls lead severe tissue destruction thus contribute accumulation clinical disability objectives subcortical atrophy ventricular enlargement using automatic segmentation pipeline 7 tesla t mri serum neurofilament light chain snfl levels neuropsychological performance patients ms irls nonirls assessed methods total 29 patients ms 15 women 24 relapsingremitting multiple sclerosis rrms five secondaryprogressive multiple sclerosis spms aged 38 2269 years expanded disability status score 2 08 disease duration 11 540 years underwent neurological neuropsychological examinations volumes lesions subcortical structures lateral ventricles 7t mri swi flair mp2rage 3d segmentation software snfl concentrations using simoa srx analyzer irl nonirl patients assessed results 1 iron rim lesions patients higher flair lesion count p 0047 patients higher mp2rage lesion volume exhibited irls p 0014 showed poorer performance information processing speed tested within 1 year using symbol digit modalities test sdmt p 0047 2 within 3 years patients showed atrophy thalamus p 0021 putamen p 0043 enlargement lateral ventricles p 0012 baseline 3 years thalamic volumes lower irls nonirl patients p 0045 3 baseline irl patients higher snfl concentrations p 0028 higher snfl concentrations associated poorer sdmt p 0004 regardless irl presence 4 irl nonirl patients showed significant difference neuropsychological performance within 1 year conclusions compared nonirl patients irl patients higher flair lesion counts smaller thalamic volumes higher snfl concentrations pilot study combines irl snfl two biomarkers considered indicative neurodegenerative processes preliminary data underscore reported destructive nature irlspmid34992573 pmcpmc8724313 doi103389 fneur2021632749,1.0
treating sarcoidosisassociated progressive multifocal leukoencephalopathy infliximab brain commun 2021 dec 16 4 1 fcab292 doi 101093 braincomms fcab292 ecollection 2022 febabstractalthough progressive multifocal leukoencephalopathy cases sarcoidosis patients explained treatment immunosuppressive drugs also reported treatmentnaive sarcoidosis patients implies general predisposition sarcoidosis patients progressive multifocal leukoencephalopathy indeed shown active sarcoidosis patients increased regulatory t cell frequencies lead subsequent systemic immunosuppression however sarcoidosis systemic changes t cell subsets frequencies constitute risk factor development progressive multifocal leukoencephalopathy counteracted sarcoidosis treatment known cohort study included characterized followedup six patients bioptically confirmed definite progressive multifocal leukoencephalopathy definite probable sarcoidosis presenting april 2013 january 2019 four immunosuppressive therapy time developing first progressive multifocal leukoencephalopathy symptoms analysis immune cell subsets patients revealed significant imbalances cd4+ t cell regulatory t cell frequencies due progression progressive multifocal leukoencephalopathy four patients decided treat sarcoidosis anticipating normalization immune cell subset frequencies thereby improving progressive multifocal leukoencephalopathy notably treatment infliximab antibody directed tumour necrosis factor three patients continuously improved clinically jc virus longer detectable cerebrospinal fluid regulatory t cell frequencies decreased one patient initially misdiagnosed neurosarcoidosis died 9 weeks treatment initiation due aspiration pneumonia study provides insight sarcoidosis can lead changes t cell subset frequencies predisposes progressive multifocal leukoencephalopathy although immunosuppressive drugs avoided progressive multifocal leukoencephalopathy paradoxically patients sarcoidosis treatment immunosuppressive infliximab might restore normal t cell distribution thereby halt progressive multifocal leukoencephalopathy progressionpmid34993476 pmcpmc8727989 doi101093 braincomms fcab292,0.0
prevalence anxiety depression patients multiple sclerosis saudi arabia crosssectional study cureus 2021 dec 29 13 12 e20792 doi 107759 cureus20792 ecollection 2021 decabstractintroduction multiple sclerosis ms chronic disease progressive demyelination central nervous system carries significant risk depression psychological difficulties associated low quality life paucity data prevalence anxiety depression saudi arabia among patients ms conducted crosssectional study determine prevalence anxiety depression saudi arabia among patients ms age disease severity compliance medication social support methods crosssectional study measured prevalence anxiety depression 184 adult patients ms patients selected random sampling method pool ms societies saudi arabia participants completed selfadministered questionnaires included demographic variables participants also completed patient health questionnaire9 phq9 general anxiety disorder7 gad7 questionnaire results depression detected among 139 755 patients ms participants mild depression 31 women 831 experienced depression men 621 p 0002 anxiety disorder present 123 668 patients ms mild anxiety n 56 304 conclusion found high rate depression anxiety among patients ms saudi arabia results highlight need periodic screening examination patients ms psychiatrists facilitate early detection treatment comorbidities potentially improving patient quality life health outcomespmid34993046 pmcpmc8720031 doi107759 cureus20792,1.0
immunoglobulin g immune response sarscov2 vaccination people living multiple sclerosis within multiple sclerosis partners advancing technology health solutions mult scler 2022 jan 713524585211061343 doi 101177 13524585211061343 online ahead printabstractbackground impact multiple sclerosis ms diseasemodifying therapies dmts sarscov2 vaccination response uncertainmethods postsarscov2 vaccination blood samples across multiple dmts tested sarscov2 immunoglobulin g igg responseresults three hundred twentytwo people ms included 919 received mrna vaccine postvaccination reactive igg rates igg index 1 40 anticd20 32 80 patients 41 sphingosine 1phosphate receptor modulators s1prm 16 39 100 classes including dmt groupconclusion anticd20 therapies s1prms reduce igg response sarscov2 vaccination igg response preserved dmtspmid34994577 doi101177 13524585211061343,0.0
visual evoked potentials neuromyelitis optica spectrum disorders j cent nerv syst dis 2021 dec 21 1311795735211057315 doi 101177 11795735211057315 ecollection 2021abstractbackground neuromyelitis optica spectrum disorders nmosds rare antibodymediated disorders central nervous system predilection spinal cord optic nerves clinical utility evoked potential recordings eps already established multiple sclerosis particular abnormal visual evoked potentials vep key criterion mcdonald diagnostic criteria ms however reports eps patients nmosdaim aim study assess possible involvement optical pathway vep responses patients nmosdmethods veps prospectively performed 13 patients nmosd patients recruited outpatient clinic demyelinating diseases center recording done recommended international federation clinical neurophysiologyresults evaluated eyes 12 women mean age 42 years one man 25 years old 6 examined eye samples response obtained remaining 20 eye samples found significant increase p100 latency without amplitude changeconclusion veps showed significant increase p100 latency vep assessment noninvasive painless fast lowcost exam provides neurophysiological data diagnosis nmosdpmid34992486 pmcpmc8724984 doi101177 11795735211057315,1.0
divergent timevarying connectivity thalamic subregions characterizes clinical phenotypes cognitive status multiple sclerosis mol psychiatry 2022 jan 7 doi 101038 s4138002101401w online ahead printabstractwe aimed investigate abnormal timevarying functional connectivity fc thalamic subregions multiple sclerosis ms clinical cognitive mri correlates eightynine ms patients 49 relapsingremitting rr ms 40 progressive p ms 53 matched healthy controls underwent neurological neuropsychological resting state fmri assessment timevarying connectivity tvc quantified using slidingwindow seedvoxel correlation analysis standard deviation fc across windows taken measure tvc mean connectivity across windows expressed static fc ms patients showed reduced tvc vs controls thalamic subregions frontotemporooccipital regions time showed increased static fc thalamic subregions structurally connected corticosubcortical regions tvc reduction mainly driven rrms pms exhibited variable pattern tvc abnormalities characterized reduced tvc frontal motor thalamic seeds defaultmode network areas increased tvc vs controls rrms posterior thalamic subregions occipitotemporoinsular cortices associated severity clinical disability compared controls cognitively preserved impaired patients showed reduced tvc anterior thalamic subregions frontal cortex cognitively impaired patients also showed increased tvc right postcentral thalamic subregion cingulate cortex postcentral gyrus vs controls cognitively preserved patients divergent patterns tvc thalamic abnormalities found rrms pms patients tvc reduction rrms may represent attempt thalamic network keep stable connections conversely increased tvc posterior thalamic subregions characterized pms cognitively impaired ms possibly reflecting maladaptive mechanismspmid34992237 doi101038 s4138002101401w,0.0
autoimmune encephalitis autoantibodies review clinical implications j appl lab med 2022 jan 5 7 1 8198 doi 101093 jalm jfab102abstractbackground autoimmune encephalitis ae common cause encephalitis review recent evidence neuroimmune condition autoantibody testing currently availablecontent clinical criteria neuroimaging electroencephalography can facilitate diagnosis ae prior obtaining autoantibody testing results lead diagnosis ae even absence recognized antibody early treatment ae found correlate improved longterm functional cognitive outcomes suggest clinical approach diagnosis based predominant area nervous system involvement results ancillary testing widely available also propose 2tiered approach acute management probable definite ae finally provide guidance longterm management aea challenging understudied areasummary much work remains done improve care patients ae understanding pathophysiology predisposing factors underlying condition steadily increases evidencebased targeted approach treatment ae still desired nonetheless looking progress made past 2 decades since discovery first autoantibodies associated ae one help feel optimistic road aheadpmid34996085 doi101093 jalm jfab102,0.0
pathobiology diagnosis current biomarkers neuromyelitis optica spectrum disorders j appl lab med 2022 jan 5 7 1 305310 doi 101093 jalm jfab150abstractbackground neuromyelitis optica spectrum disorder nmosd characterized chronic inflammation central nervous system cns particularly optic nerves spinal cord although displays clinical features similar multiple sclerosis ms etiology treatment distinct therefore accurate diagnosis essential autoantibodies targeting water channel protein aquaporin4 aqp4 myelin sheath protein myelin oligodendrocyte glycoprotein major antigenspecific serological biomarkers known date destruction astrocytes primary mode cns damage aqp4positive diseasecontent minireview summarizes pathobiology clinical features current methods serological testing used assess nmosd differentiate disorder ms brief summary emerging therapies also presentedsummary nmosd can distinguished ms combination clinical findings imaging investigations serological analysis seronegative cases particularly difficult diagnose can pose challenge clinicians knowledge deepens new therapies biomarkers expected improve treatment rare debilitating diseasepmid34996075 doi101093 jalm jfab150,1.0
facial myokymia presenting feature multiple sclerosis pract neurol 2022 jan 6practneurol2021003268 doi 101136 practneurol2021003268 online ahead printno abstractpmid34992095 doi101136 practneurol2021003268,0.0
diagnostic features tuberous sclerosis complex case report literature review quant imaging med surg 2022 jan 12 1 846861 doi 1021037 qims21412abstracttuberous sclerosis complex tsc rare autosomal dominant genetic syndrome caused mutations tumour suppressor genes tsc1 tsc2 causes multiorgan growths tsc presents age wide range clinical phenotypic manifestations varying severity main goal article state two cases tsc review commonly reported major minor diagnostic clinical features common features led investigation possible tsc diagnosis herein report two cases tsc presented seizures first 6 months life case 1 presented multiple types seizures 6 months age diagnosed multiple calcified subependymal nodules sens detected computed tomography magnetic resonance imaging mri case 2 presented seizures 3 months age diagnosed prenatally tumour seen heart antenatal ultrasonography conclusion literature review revealed neurological manifestations mainly seizures main feature led investigation diagnosis tsc followed abdominal manifestations mainly renal features antenatal followup imaging manifestations skin chest eyes teeth heart rarely led tsc diagnosis cases tsc incidentally discovered medical imaging cortical tubers sens subependymal giant cell astrocytomas brain lesions commonly reported major features skin features including angiofibromas ungual fibromas shagreen patch second common major features reported literature however skin manifestations common led investigation diagnosis tsc renal features mainly angiomyolipomas amls third common major feature reported medical imaging plays essential role diagnosis tsc clinical features important clues lead investigation diseasepmid34993123 pmcpmc8666790 doi1021037 qims21412,0.0
phenotyping multiple sclerosis lesions according innate immune cell activation using 18 kda translocator proteinpet brain commun 2021 dec 22 4 1 fcab301 doi 101093 braincomms fcab301 ecollection 2022 febabstractchronic active lesions promotors neurodegeneration disease progression multiple sclerosis harbour dense rim activated innate immune cells lesion edge promotes lesion growth thereby induces damage conventional mri limited help identifying chronic active lesions alternative imaging modalities needed objectives develop petbased automated analysis method phenotyping chronic lesions based lesionassociated innate immune cell activation comprehensively evaluate prevalence lesions various clinical subtypes multiple sclerosis association disability work use 18 kda translocator proteinpet imaging phenotyping chronic multiple sclerosis lesions large scale identified 1510 white matter t1hypointense lesions 91 multiple sclerosis patients 67 relapsingremitting patients 24 secondary progressive patients innate immune cell activation lesion rim measured using pet imaging 18 kda translocator proteinbinding radioligand 11cpk11195 t1hypointense lesion classified rimactive distribution volume ratio 11cpk11195binding low plaque core considerably higher plaque edge significant ligand binding observed lesion classified inactive plaques considerable ligand binding core rim classified overallactive conventional mri disability assessment using expanded disability status scale performed time pet imaging secondary progressive cohort average 19 median interquartile range 1126 t1 lesions rimactive individual patient compared 10 interquartile range 020 among relapsingremitting patients p 0009 secondary progressive patients median 3 range 011 rimactive lesions versus 1 range 018 among relapsingremitting patients p 0029 among patients rimactive lesions n 63 average number active voxels rim higher among secondary progressive compared relapsingremitting patients median 158 versus 74 p 0022 number active voxels rim correlated significantly expanded disability status scale r 043 p 0001 volume rimactive lesions similarly correlated expanded disability status scale r 045 p 0001 study first report vivo phenotyping chronic lesions large scale based 18 kda translocator proteinpet patients higher disability displayed higher proportion rimactive lesions vivo lesion phenotyping methodology offers new tool individual assessment smouldering rimactive lesion burdenpmid34993478 pmcpmc8727984 doi101093 braincomms fcab301,0.0
prediction longterm mortality using machine learning models chinese patients connective tissue diseaseassociated interstitial lung disease background exact risk assessment crucial management connective tissue diseaseassociated interstitial lung disease ctdild patients present study develop nomogram predict 3 5year mortality using machine learning approach test ildgap model chinese ctdild patientsmethodsctdild patients diagnosed treated first affiliated hospital zhengzhou university enrolled based prior welldesigned criterion february 2011 july 2018 cox regression least absolute shrinkage selection operator lasso used screen predictors generate nomogram internal validation performed using bootstrap resampling nomogram ildgap model assessed via likelihood ratio testing harrells c index integrated discrimination improvement idi net reclassification improvement nri decision curve analysisresultsa total 675 consecutive ctdild patients enrolled study median followup period 50 interquartile range 3865 months 158 patients died mortality rate 234 feature selection 9 variables identified age rheumatoid arthritis lung diffusing capacity carbon monoxide right ventricular diameter right atrial area honeycombing immunosuppressive agents aspartate transaminase albumin predictive nomogram generated integrating variables provided better mortality estimates ildgap model based likelihood ratio testing harrells c index 0767 0652 respectively calibration plots application nomogram resulted improved idi 3 5year 0137 0136 respectively nri 3 5year 0294 0325 respectively compared ildgap model addition nomogram clinically useful revealed decision curve analysisconclusionsthe results study prove ildgap model may exhibit inapplicable role predicting mortality risk chinese ctdild patients nomogram developed performed well predicting 3 5year mortality risk chinese ctdild patients studies external validation will required determine clinical usefulness nomogram,0.0
exposure silicates systemic autoimmunerelated outcomes rodents systematic review background autoimmunity can result interplay genetic background effects environmental occupational exposure hazardous materials several compounds including silica dust linked systemic autoimmunity systemic autoimmune diseases based epidemiological evidence asbestos strong link systemic autoimmune diseases yet exist however several studies documented features autoimmunity following asbestos exposure even human studies limited ability identify examine isolated exposures making difficult demonstrate causation assess pathogenic mechanisms therefore systematic review examines existing animal evidence regarding autoimmunity exposure silicates silica asbestos methodspubmed embase systematically searched peerreviewed studies examining systemic autoimmune diseaserelated outcomes silicate exposure rodents literature databases searched september 2021 studies written english full text available search strings established based peco population exposure comparator outcome format title abstract fulltext screening thirtyfour studies identified analysis quality assessment toxr tool qualitative analysis results performedresultsalthough significant heterogeneity included studies terms exposure protocol genetic background rodent models used noted genetic background exposure silicates crystalline silica asbestos highly relevant development sub clinical systemic autoimmune diseaseconclusionparallels observed findings animal review human epidemiological studies arguing experimental animal models valuable tools examining exacerbation development autoimmune disease silicate exposure however genetic background synergism exposures considered future studies,0.0
clinical characteristics outcomes multiple sclerosis patients covid19 toronto canada abstractobjective report clinical characteristics outcomes people multiple sclerosis pwms developed covid19 infection toronto canadamethods descriptive retrospective singlecenter study included known pwms st michaelnulls hospital ms clinic pcrconfirmed covid19 infection march 2020 may 2021results 7000 pwms clinic 80 11 tested positive sarscov2 fiftyfour 675 diseasemodifying therapy dmt without overrepresentation single treatment seventyone patients 888 mild symptoms nine 113 hospitalized one 70yearold male patient treatment died hospitalized onethird treated ocrelizumabconclusion toronto pwms appear higher prevalence covid19 infection compared general population disease severity may affected dmt use findings add accumulating global data regarding covid19 infection pwms,0.0
platelettolymphocyte ratio differs ms nmosd disease onset predict disability abstractbackground aimed assess platelettolymphocyte plr neutrophiltolymphocyte ratios nlr differentiating multiple sclerosis ms aquaporin4antibodypositive neuromyelitis optica spectrum disorders nmosd disease onsetmethods nwe retrospectively enrolled reviewed medical records patients ms n50 nmosd n33 followed specialized ms nmosd centers argentina demographical clinical manifestation disability data neuroradiological features new enlarging contrastenhancing lesions assessed baseline 1 2 years serum samples obtained first relapse without previous acute chronic treatment 1 2 years mixedeffects model used identify independent associations logtransformed nlr plr ms nmosd outcomesresults plr increased nmosd compared ms 2294 8674 vs 1866 7017 p001 significant differences found nlr 351 129 vs 330 117 p043 plr independent predictor poor physical disability score edss 4 nmosd patients 2 years 028 p002 applying multivariate regression analysis additionally multivariate logistic regression analysis showed plr independent predictor edss 4 2 years 288 p0041 nmosd group area receiveroperating characteristic curve 0841conclusion plr potentially useful additional diagnostic tool differentiating two neuroinflammatory conditions presentation plr can predict severity neurological disability 2 years nmosd patients,0.0
study brain functional network alertness changes temporal lobe epilepsy without focal bilateral tonicclonic seizures background temporal lobe epilepsy tle commonly refractory epilepsy surgery effective treatment strategy refractory epilepsy patients history focal bilateral tonicclonic seizures fbtcs poor outcomes previous network studies epilepsy found tle idiopathic generalized epilepsy generalized tonicclonic seizures igegtcs showed altered global nodal topological properties alertness deficits also found tle however fbtcs common type seizure tle implications alertness well topological rearrangements associated seizure type well understoodmethodswe obtained rsfmri data collected neuropsychological assessment data 21 tle patients fbtcs tle fbtcs 18 tle patients without fbtcs tlenon fbtcs 22 controls constructed respective functional brain networks topological properties analyzed using graph theoretical approach correlations altered topological properties alertness analyzedresultswe found tlefbtcs patients showed serious impairment alertness effect intrinsic alertness phasic alertness patients tlenonfbtcs also showed significantly higher smallworldness normalized clustering coefficient trend higher global network efficiency ge compared tlenonfbtcs patients ge showed significant negative correlation intrinsic alertness tlenonfbtcs patientsconclusionour findings show different impairments brain network information integration segregation alertness patients tlefbtcs tlenonfbtcs demonstrating impairments brain network may underlie disruptions alertness functions,0.0
dialectical behavior therapy skills training individuals multiple sclerosis support partners pilot randomized controlled trial abstractbackground symptoms anxiety depression emotion dysregulation common among individuals ms support partners dialectical behavior therapy dbt type cognitive behavioral intervention may promising treatment individuals affected ms pilot randomized controlled trial rct assessed effects feasibility remotely delivered dbt skills anxiety depression symptoms emotion dysregulation individuals ms support partnersmethods study featured singlemasked twoarm parallel group design twenty pairs individuals ms support partners n40 randomized 12 weeks dbt facilitated peer support fps masked assessments completed weeks 0 baseline 13 postintervention 26 followup results postintervention primary endpoint participants randomized dbt exhibited significantly greater reductions anxiety depression symptoms compared fps b445 p04 cohennulls d057 secondary outcomes emotion dysregulation wellbeing favored dbt group reach statistical significance ds051 ps07 effects maintained followup 86 individuals screened eligible trial retention 70 differ study armsconclusions pilot rct provides encouraging evidence dbt skills feasible may improve depression anxiety emotion dysregulation individuals ms support partners future research needed optimize maintenance dbt skills investigate mechanisms improvements replicate promising effects fully powered trial,0.0
hlaspread natural language processing based resource curating hla association pubmed abstracts abstractextreme complexity human leukocyte antigens hla system nomenclature makes difficult interpret integrate relevant information hla associations diseases adverse drug reactions adr transplantation pubmed search displays 146 000 studies hla reported diverse locations currently ipdimgt hla robinson et al nucleic acids research 48d948d955 2019 database houses data 28 320 hla alleles developed automated pipeline unified graphical user interface hlaspread provides structured information snps populations resources adrs diseases information information hla extracted 28 million pubmed abstracts extracted using natural language processing nlp python scripts used mine curate information diseases filter false positives categorize 24 tree hierarchical groups named entity recognition ner algorithms followed semantic analysis infer hla association s resource 109 countries 40 ethnic groups provides interesting insights markers associated allelic haplotypic association autoimmune cancer viral skin diseases transplantation outcome adrs hypersensitivity summary information clinically relevant biomarkers related hla disease associations mapped susceptible risk alleles readily retrievable hlaspread resource available url http hlaspreadigibresin resource first kind can help uncover novel patterns hla genedisease associations,0.0
comparing diagnostic criteria diagnosis neurocognitive disorders multiple sclerosis abstractbackgroundpeople multiple sclerosis ms commonly experience cognitive impairment associated disease currently agreedupon operational definition identifying presence impairment either research clinic contexts international ms cognition society imscogs established task force begin examine issue paper represents results initial pilot investigation aim paper compare two criterion sets determine identify cognitive impairment among people ms general diagnostic statistical manual dsm5 criteria neurocognitive disorders criteria derived existing ms research scores two domains fall 15 standard deviations normative controls methodstwo hundred ten people ms presented brief cognitive evaluation ms multidisciplinary clinic midwestern academic medical center united states participants generally middle aged average 515 years female 738 white 933 mcnemarnulls test computed compare number individuals whose cognitive test score performance deemed cognitively normal mildly impaired significantly impairedresultsdsm5 criteria classified 872 sample cognitively impaired 667 mildly impaired 205 significantly impaired contrast researchbased criteria classified 633 sample cognitively impaired 495 mildly impaired 138 significantly impairedconclusionsthese findings indicate compared research criteria dsm5 criteria classified far people ms cognitive impairment secondary disease paper discusses potential benefits drawbacks two diagnostic methods highlighting work will needed order establish standardized validated method characterizing impairments,0.0
integrative analysis 3604 gwas reveals multiple novel cell typespecific regulatory associations background genomewide association study gwas single nucleotide polymorphisms snps known preferentially colocate active regulatory elements tissues cell types relevant disease aetiology characterisation associated cell typespecific regulation can broaden understanding gwas signals may contribute disease riskresultsto gain insight potential functional mechanisms underlying gwas associations developed forge2 https forge2altiusinstituteorg updated version forge web tool forge2 uses expanded atlas cell typespecific regulatory element annotations including dnase hotspots five histone mark categories 15 hidden markov model hmm chromatin states identify tissue cell typespecific signals analysis 3 604 gwas nhgriebi gwas catalogue yielded least one significant disease traittissue association 2 057 gwas including 400 associations specific epigenomic marks immune tissues cell types 30 associations specific heart tissue 60 associations specific brain tissue highlighting key potential tissue cell typespecific regulatory elements importantly demonstrate forge2 analysis can separate previously observed accessible chromatin enrichments different chromatin states enhancers active transcription start sites providing greater understanding underlying regulatory mechanisms interestingly tissuespecific enrichments repressive chromatin states histone marks also detected suggesting role tissuespecific repressed regions gwasmediated disease aetiologyconclusionin summary demonstrate forge2 potential uncover previously unreported diseasetissue associations identify new candidate mechanisms forge2 transparent userfriendly web tool integrative analysis loci discovered gwas,0.0
feasibility virtual realitybased exercise intervention lowcost motion tracking method estimation motor proficiency youth autism spectrum disorder background motor impairment widely acknowledged core feature children autism spectrum disorder asd can affect adaptive behavior increase severity symptoms lowcost motion capture virtual reality vr game technologies hold great deal promise providing personalized approaches motor intervention asd present study explored feasibility acceptability potential efficacy customdesigned vr gamebased intervention gaitwayxr improving gross motor skills youth asdmethodsten children adolescents 1017 years completed six 20min vrbased motor training sessions 2 weeks wholebody movement tracked lowcost motion capture system developed methodology using motion tracking data quantify wholebody movement terms efficiency synchrony symmetry studied relationships quantities standardized measures motor skill cognitive flexibilityresultsour results supported presumption vr intervention safe adverse events minor moderate sideeffects large proportion parents said use vr game home prohibitive reasons adopting system home therapy cost space although little evidence benefits gaitwayxr intervention improving gross motor skills showed several positive correlations standardized measures gross motor skills asd measures efficiency symmetry synchrony lowcost motion captureconclusionsthese findings though preliminary limited small sample size suggest lowcost motion capture children asd feasible movement exercises vrbased game environment based preliminary findings recommend conducting largerscale studies methods improving adherence vr gaming interventions longer periods,0.0
antiinflammatory agent bindarit attenuates impairment neural development suppression microglial activation neonatal hydrocephalus mouse model neonatal hydrocephalus presents various degrees neuroinflammation longterm neurological deficits surgically treated patients provoking need additional medical treatment previously reported elevated neuroinflammation severe periventricular white matter damage progressive hydrocephalus prh mutant contains point mutation ccdc39 gene causing loss ciliamediated unidirectional cerebrospinal fluid csf flow study identified cortical neuropil maturation defects impaired excitatory synapse maturation loss homeostatic microglia swimming locomotor defects early postnatal prh mutant mice strikingly systemic application antiinflammatory small molecule bindarit significantly supports healthy postnatal cerebral cortical development prh mutant bindarit mildly reduced ventricular volume significantly improved edematous appearance myelination corpus callosum moreover treatment attenuated thinning cortical layers iiiv excitatory synapse formation interneuron morphogenesis supporting ramifiedshaped homeostatic microglia excessive cell death also therapeutic effect led alleviation spastic locomotor phenotype mutant found microglia peripheral monocytes contribute amoeboidshaped activated myeloid cells prh mutants corpus callosum proinflammatory cytokines expression bindarit blocks nfkb activation downstream proinflammatory cytokines including monocyte chemoattractant protein1 prh mutant collectively revealed amelioration neuroinflammation crucial white matter neuronal maturation neonatal hydrocephalus future studies bindarit treatment combined csf diversion surgery may provide longterm benefits supporting neuronal development neonatal hydrocephalussignificance statementin neonatal hydrocephalus little known signalling cascades neuroinflammation impact inflammatory insults neural cell development within perinatal cerebral cortex report proinflammatory activation myeloid cells majority derived microglia impairs periventricular myelination cortical neuronal maturation using mouse prh genetic model neonatal hydrocephalus administration bindarit antiinflammatory small molecule blocks nfkb activation restored cortical thinning synaptic maturation defects prh mutant brain suppression microglial activation data indicate potential therapeutic use antiinflammatory reagents targeting neuroinflammation treatment neonatal hydrocephalus,1.0
higher levels igg3 antibodies serum csf distinguish multiple sclerosis neurological disorders j neuroimmune pharmacol 2022 jan 6 doi 101007 s1148102110048x online ahead printabstractincreased intrathecal igg oligoclonal bands ocb seminal features multiple sclerosis ms although differences ms blood total igg antibodies reported serum ocb common persistent finding ms systemic source recent studies showed igg3+ b cells higher levels serum igg3 linked development ms additionally intrathecal igg synthesis ms associated igg3 heavy chain gene single nucleotide polymorphisms strong relationship susceptibility ms igg3 restriction fragment length polymorphism studies support role igg3 disease pathogenesis using multiple immunoassays investigated levels total igg igg1 igg3 sera csf 102 ms patients 19 paired csf sera 76 patients neurological disorders 9 paired csf sera 13 healthy controls show higher levels total igg igg3 antibodies detected ms serum csf distinguishes ms inflammatory noninflammatory neurological disorders receiver operating characteristic roc curves 079 igg3 total igg data support notion igg3 antibodies may potential candidate ms blood biomarker developmentpmid34989971 doi101007 s1148102110048x,0.0
effects modified curcumin preparations glial morphology aging neuroinflammation neurochem res 2022 jan 6 doi 101007 s11064021034994 online ahead printabstractneuroinflammation characterized reactive microglia astrocytes collectively called gliosis central nervous system considered one main pathological hallmarks different neurodegenerative diseases alzheimers disease agerelated dementia multiple sclerosis upon activation glia undergoes structural morphological changes microglial cells swell size astrocytes become bushy play beneficial detrimental roles hence unable perform normal physiological role brain immunity curcumin cytokine suppressive antiinflammatory drug high proven preclinical potency efficacy reverse chronic neuroinflammation attenuating activation morphological changes occur microglia astrocytes review will highlight recent findings tree structure changes microglia astrocytes neuroinflammation effects curcumin activation morphology glial cellspmid34988899 doi101007 s11064021034994,0.0
clinical heterogeneity patients myoclonus associated covid19 neurol sci 2022 jan 6 doi 101007 s10072021058021 online ahead printabstractobjective study aims report clinical heterogeneity myoclonus 6 patients infected severe acute respiratory syndrome coronavirus 2 sarscov2 methods patient data obtained medical records university hospital dr josep trueta girona spainresults six patients 5 men 1 woman aged 6076 years presented different myoclonus phenotypes medical history hypertension overweight latency myoclonus appearance ranged 1 129 days phenotype observed generalized myoclonus special phenotypes painful legs moving toes syndrome jerking feet lazarus signlike action myoclonus ataxia syndrome segmental myoclonus secondary myelitis described levetiracetam clonazepam medications used successfully two patients died complications related myoclonusconclusions 6 cases highlight heterogeneity clinical spectrum myoclonus associated covid19 myaco myaco pathogenesis suspected due immunemediated para postinfectious phenomenon nevertheless research needed elucidate hypothesispmid34988717 doi101007 s10072021058021,0.0
characterization definitive regulatory b cell subsets cell surface phenotype function context front immunol 2021 dec 20 12787464 doi 103389 fimmu2021787464 ecollection 2021abstractregulatory b cell breg broad term represents antiinflammatory activity b cells describe individual phenotypes specific mechanisms regulation relevant disease contexts thus given variety b cell regulatory mechanisms reported human disease animal models thorough comprehensive identification strategy needed tracking comparing b cell subsets research groups clinical settings review summarizes discovery process mechanism action welldefined regulatory b cell subsets emphasis mouse model multiple sclerosis experimental autoimmune encephalomyelitis discuss importance conducting thorough b cell phenotyping along mechanistic studies prior defining particular subset b cells breg since virtually b cell subsets can exert regulatory activity timely definitive identification across studiespmid34987513 pmcpmc8721101 doi103389 fimmu2021787464,0.0
transcriptional analysis nuclearencoded mitochondrial genes eight neurodegenerative disorders analysis seven diseases reference friedreich#39 s ataxia front genet 2021 dec 20 12749792 doi 103389 fgene2021749792 ecollection 2021abstractneurodegenerative diseases ndds challenging understand diagnose treat revealing genomic transcriptomic changes ndds contributes greatly understanding diseases causes development moreover enables precise genetic diagnosis novel drug target identification potentially treat diseases least ease symptoms study analyzed transcriptional changes nuclearencoded mitochondrial nem genes eight ndds specifically address association genes diseases previous studies show strong links defects nem genes neurodegeneration yet connecting specific genes ndds well studied friedreichs ataxia frda ndd treated effectively therefore focused first frda compared outcome seven ndds including alzheimers disease amyotrophic lateral sclerosis creutzfeldtjakob disease frontotemporal dementia huntingtons disease multiple sclerosis parkinsons disease first weighted correlation network analysis performed frda rnaseq data set focusing nem genes carried differential gene expression analysis pathway enrichment analysis pinpoint differentially expressed genes potentially associated one analyzed ndds findings propose strong link nem genes ndds suggest identified candidate genes can potentially used diagnostic markers therapeutic targetspmid34987545 pmcpmc8721009 doi103389 fgene2021749792,0.0
diagnosis multiple sclerosis disease brain magnetic resonance imaging based harris hawks optimization algorithm biomed res int 2021 dec 27 20213248834 doi 101155 2021 3248834 ecollection 2021abstractthe damaged areas brain tissues can extracted using segmentation methods based integration machine learning data mining techniques important segmentation method utilize clustering techniques especially fuzzy cmeans fcm clustering technique sufficiently accurate overly sensitive imaging noise therefore fcm technique appropriate multiple sclerosis diagnosis although optimal selection cluster centers can affect segmentation difficult select nphard problem study harris hawks optimization hho algorithm used optimal selection cluster centers segmentation fcm algorithms hho accurate conventional algorithms genetic algorithm particle swarm optimization proposed method every membership matrix assumed hawk hho member next step generate population hawks membership matrices optimal selected find optimal cluster centers decrease multiple sclerosis clustering error according tests conducted number brain mris proposed method outperformed fcm clustering techniques knn algorithm support vector machine hybrid data mining methods accuracypmid34988224 pmcpmc8723867 doi101155 2021 3248834,0.0
salvinorin analogue ethoxymethyl ether salvinorin b promotes remyelination preclinical models multiple sclerosis front neurol 2021 dec 20 12782190 doi 103389 fneur2021782190 ecollection 2021abstractmultiple sclerosis neurodegenerative disease associated demyelination neuroinflammation central nervous system urgent need develop remyelinating therapies better treat multiple sclerosis demyelinating diseases kappa opioid receptor kor identified potential target development remyelinating therapies however prototypical kor agonists u50 488 side effects limit clinical use current study investigated salvinorin analog ethoxymethyl ether salvinorin b eom salb two preclinical models demyelination c57bl 6j mice showed cellular assays eom salb gprotein biased effect often correlated fewer kormediated side effects experimental autoimmune encephalomyelitis model found eom salb 0103 mg kg effectively decreased disease severity kordependent manner led greater number animals recovery compared u50 488 treatment furthermore eom salb treatment decreased immune cell infiltration increased myelin levels central nervous system cuprizoneinduced demyelination model showed eom salb 03 mg kg administration led increase number mature oligodendrocytes number myelinated axons myelin thickness corpus callosum overall eom salb effective two preclinical models multiple sclerosis demyelination adding evidence show kor agonists promising target remyelinating therapiespmid34987466 pmcpmc8721439 doi103389 fneur2021782190,1.0
neural correlates dualtask walking people central neurological disorders systematic review j neurol 2022 jan 6 doi 101007 s00415021109445 online ahead printabstractbackground people central neurological disorders experience difficulties dualtask walking due diseaserelated impairments objective review provide comprehensive examination neural correlates structural functional brain changes dualtask walking people parkinsons disease pd multiple sclerosis ms stroke alzheimers disease ad methods systematic review literature conducted following prisma guidelines medline embase scopus included studies examined relationship structural functional brain imaging dualtask walking performance people pd ms stroke ad articles met inclusion criteria baseline characteristics study design behavioral brain outcomes extracted twentythree studies included reviewresults structural imaging studies 75 found association decreased brain integrity poor dualtask performance specific brain regions showed association include striatum regions hippocampus pd supplementary motor area ms functional imaging studies reported association increased prefrontal activity maintained compensatory recruitment decreased dualtask walking performance pd stroke subset n 2 stroke papers found significant correlations increased supplementary motor area activity associated decreased performance ms stroke studies ad identifiedconclusion people pd ms stroke several neural correlates dualtask walking identified however direction association neural performance outcomes varied across studies type cognitive task used presentation modality eg visual may contributed mixed findingspmid34989867 doi101007 s00415021109445,0.0
diagnostic value lumbar puncture etiological assessment uveitis retrospective cohort 188 patients graefes arch clin exp ophthalmol 2022 jan 6 doi 101007 s00417021055144 online ahead printabstractaim assess relevance lumbar puncture lp etiological diagnosis uveitis establish predictive factors associated contributory usemethods performed retrospective study patients de novo uveitis referred tertiary hospital etiological diagnosis uveitis january 2003 july 2018 included patients underwent lp part etiological assessment uveitis lp considered contributory led etiological diagnosis correct initially suspected diagnosisresults one hundred eighty eight 1211 patients referred evaluation 16 lp among patients 93 494 abnormal results including 69 367 patients hypercellularity 69 367 hyperproteinorachia 28 149 oligoclonal bands increased igg index lp considered contributing diagnosis 31 164 cases among 10 53 contributions etiological diagnosis 21 112 modifications diagnosis classification multivariate analysis established african ethnicity p 0001 bilateral uveitis p 001 presence macular edema retinal serous detachment p 0048 presence retinal vasculitis p 0001 presence neurological signs symptoms p 001 contributing cerebral mri p 0001 significantly associated contributory lp lp lead therapeutic modificationconclusion lp direct contribution diagnosis rare often detected nonspecific abnormalities lp performed cases neurological clinical signs symptoms suspicion multiple sclerosis vogtkoyanagiharada syphilispmid34988612 doi101007 s00417021055144,0.0
lack association c282y h63d polymorphisms hemochromatosis gene risk multiple sclerosis metaanalysis biomed rep 2022 feb 16 2 12 doi 103892 br20211495 epub 2021 dec 17abstractincreasing evidence supports potential role iron metabolism multiple sclerosis ms previous studies examining association polymorphisms hemochromatosis gene hfe susceptibility ms yielded inconsistent results present study metaanalysis 7 studies performed conducted populations caucasian origin using comprehensive metaanalysis 30 software strength association c282y h63d polymorphisms hfe ms risk estimated odds ratios 95 confidence intervals cochrans q statistic i2 tests applied quantify heterogeneity studies eggers test used estimate publication bias c282y h63d polymorphisms significant association increased ms risk p005 following genetic comparison models dominant model yy + cy vs cc dd + hd vs hh allele contrast y vs c d vs h apparent publication bias significant heterogeneity found studies results suggest hfe polymorphisms c282y h63d associated susceptibility ms populations caucasian origin studies performed larger series ms patients evaluate contribution hfe genetic variants associated iron regulation development progression mspmid34987796 pmcpmc8719312 doi103892 br20211495,0.0
masked face recognition patients relapsingremitting multiple sclerosis ongoing covid19 pandemic neurol sci 2022 jan 6 doi 101007 s10072021057979 online ahead printabstractbackground face facial expression recognition abilities frequently evaluated assessment social cognition disorders patients ms investigation effect new difficulties emerging field face recognition widespread use masks ongoing covid19 pandemic patients ms may make new contributions literaturematerial methods study included 44 patients relapsingremitting ms rrmsp 51 controls matched case group terms age education level benton face recognition testshort form bfrtsf beck depression inventory closeended 13item survey face recognition difficulties due mask use pandemic administered groupsresults rrmsp mean disease duration 82 56 mean edss score 12 10 mean moca test score 2723 208 mean bfrtsf 199 24 rrmsp 216 18 healthy controlstwentyfive percent rrmsp 4 healthy controls required people remove masks able recognize faces improvement face recognition difficulty time reported 80 healthy controls 34 rrmspconclusion rrmsp worse performance masked face recognition required removal facial masks often healthy controls recognize faces rrms patients show much improvement recognizing masked faces time according onset pandemic healthy controlspmid34988718 doi101007 s10072021057979,0.0
adaptation validation hamburg quality life questionnaire multiple sclerosis haquams use iranian patients acta neurol taiwan 2022 jan 25 31 1 2435abstractpurpose quality life qol considered important criterion therapeutic effectiveness therefore present study aimed validate persian version hamburg quality life questionnaire multiple sclerosis haquams use iranian people msmethods crosssectional study 158 people ms selected census sampling method construct validity persian version haquams first evaluated confirmatory factor analysis cfa amos22 software internal consistency reliability itemtotal score correlations calculated subscale spss22results cfa output results indicated haquams fivefactor structure among iranian ms patients good construct validity item eliminated number covariance errors items released rmsea euqal 0069 internal consistency haquams subscales acceptable excellent alpha euqal 081 091 analysis itemtotal score correlation determining construct validity haquams indicated items questionnaire moderate strong positive correlation subscales p less 00001 r euqal 041 089 correlation total scores haquams beck depression inventoryshort form bdi13 equal 074 p less 00001 indicating good concurrent criterion validityconclusion persian version haquams fivefactor construct acceptable validity reliability used measurement health related qol iranian people mspmid34988951,0.0
effect month birth multiple sclerosis sasecontrol study northeast iran acta neurol taiwan 2022 jan 25 31 1 714abstractbackground multiple sclerosis ms autoimmune multifactorial eg environmental genetic disease conducted casecontrol study month season birth mob sob multiple sclerosis ms risk east iranmethods ms patients registered mashhad torbat heydariyeh ms society 20 march 2018 compared mob sob healthy population 1988 2018 case group matched age sex place residence control group differences distributions mob sob patients control groups assessed using chisquare testresults 2 160 ms patients case group 2 245 control group significant relationship mob ans sob risk ms p less 005 analysis showed significant p less 001 peak mob marapr equal 160 mayjun equal 130 augsep equal 242 conclusion findings show relationship mob sob risk factor ms northeast iran studies needed confirm result keyword multiple sclerosis month birth seasonality casecontrol iranpmid34988949,0.0
lipopolysaccharide induced altered signaling pathways various neurological disorders naunyn schmiedebergs arch pharmacol 2022 jan 6 doi 101007 s00210021021989 online ahead printabstractneuroinflammation defined inflammatory response within brain spinal cord whereas brains innate immune system triggered various inflammatory challenges injury infection exposure toxin lps ageing result cognitive impairment neurodegenerative diseases including alzheimers disease ad parkinsons disease pd amyotrophic lateral sclerosis als multiple sclerosis ms lipopolysaccharide lps main structural component outer membrane gramnegative bacteria widely used systematically stimulate immune system generate profound physiological behavioural changes consists three parts lipid core oligosaccharide o side chain reported several scientists besides systemic alteration lps also induces neurodegeneration promoting neuroinflammation upon binding stimulation tolllike receptor4 tlr4 receptors present glial cells mammalian tolllike receptor tlr family consists 13 membranes tlr discovered crucial pattern recognition receptor ppr involved recognition pathogenassociated molecular patterns pamps future studies will show damage dangerassociated molecular patterns damps recognised involvement pprs generated host stimulation tlr4 lipopolysaccharide phosphorylates two signalling pathways namely myd88dependent pathway myd88independent pathway activation subsequently triggers release various proinflammatory cytokines necessary activate innate immune responses promotes neuroinflammation review critically demonstrated epidemiology neuroinflammation types tlrs molecular mechanism tlr4 management neuroinflammationpmid34989812 doi101007 s00210021021989,0.0
establishment human induced pluripotent stem cells multiple sclerosis patients methods mol biol 2022 jan 6 doi 101007 7651_2021_453 online ahead printabstractthe patientderived ipsc lines provide valuable resources cells can utilized generate human cell types relevant disease interest context human ipscbased model systems particularly useful neurological diseases neuron glial cell types affected diseases difficult obtain multiple sclerosis demyelinating central nervous system disease characterized inflammation eventually axonal damage ips cells generated ms patients may allow unique approaches studying disease speciesspecific manner potentially limitless supply patients glial neuronal cells differentiated ipscs describe detailed protocol establishing ipscs peripheral blood mononuclear cells utilized model multiple sclerosis particularly focused optimized costeffective procedures using integrationfree sendai virusbased reprogramming method generation characterization ms ipscspmid34988943 doi101007 7651_2021_453,1.0
assessment peripheral biomarkers potentially involved episodic chronic migraine casecontrol study focus ngf bdnf vegf pge2 background several inflammatory vascular molecules neurotrophins suggested possible role development migraine however pathophysiological events leading migraine onset transformation episodic migraine em chronic migraine cm fully understood thus aimed assess peripheral levels nerve growth factor ngf brainderived neurotrophic factor bdnf vascular endothelial growth factor vegf prostaglandin e2 pge2 em cm patients controlsmethodsfrom september 2017 june 2020 89 subjects enrolled casecontrol study 23 36 em cm patients respectively 30 age sexmatched controls demographic data medical history obtained patients headache characteristics recorded baseline visit ensuing 30 days persons migraine disease serum levels ngf bdnf vegf pge2 measured controls em cm patients adjusted age sex body mass indexresultsserum levels ngf significantly lower em patients compared controls cm patients pvalue0003 0042 respectively serum levels bdnf significantly lower em cm patients opposed controls pvalue0001 comparable em cm patients pvalue0715 peripheral blood levels vegf significantly higher em cm patients opposed controls pvalue0001 different em cm patients pvalue0859 serum levels pge2 significantly lower em patients compared controls pvalue0011 however similar em cm patients pvalue0086 migraine patients serum levels ngf pge2 positively correlated headache frequency ngf 0476 pvalue0001 pge2 0286 pvalue0028 corresponding levels bdnf vegf correlate headache frequency bdnf 0037 pvalue0778 vegf 0025 pvalue0850 conclusionsour findings suggest ngf bdnf pge2 vegf may play significant role migraine pathogenesis chronification therefore might bear potential value novel targeted abortive prophylactic migraine therapy prospective cohort studies larger sample sizes can robustly evaluate implications findings,0.0
computerized cognitive training people depression protocol systematic review metaanalysis background people depression often present concurrent cognitive impairment computerized cognitive training cct safe efficacious strategy maintain enhance cognitive performance range clinical populations however efficacy people depression varies across populations design factors currently unclearmethodswe searched medline embase psycinfo inception 13 july 2021 randomised controlled trials examining efficacy cct vs control condition cognitive mood psychiatric symptoms psychosocial daily functioning adults depression eligible samples include studies specifically targeting people major depressive disorder well diagnoses least 50 sample meets clinical criteria depression exception major psychiatric disorders dementia primary outcome change overall cognitive performance multivariate analyses will used examine effect sizes outcome category well possible effect modifiers correlations categories risk bias will assessed using cochrane risk bias tool version 2discussionto best knowledge will first systematic review metaanalysis narrowly defined cct across clinical populations depression aim investigate whether cct efficacious cognition also effects vary across design factors clinically relevant outcomes might respond cct extent differ across populationssystematic review registrationprospero crd42020204209,0.0
military traumatic brain injury challenge straddling neurology psychiatry abstractmilitary psychiatry new subcategory psychiatry become invaluable intangible effect war review begin examining related military research summarizing related epidemiological data neuropathology research achievements diagnosis treatment technology discussing comorbidity sequelae date advances neuroimaging molecular biology greatly boosted studies military traumatic brain injury tbi particular terms pathophysiological mechanisms several preclinical studies identified abnormal protein accumulation bloodbrain barrier damage brain metabolism abnormalities involved development tbi important concept field psychiatry tbi based organic injury largely different many mental disorders therefore military tbi neuropathic psychopathic emerging challenge intersection neurology psychiatry,0.0
small fiber neuropathy assessment disease severity amyotrophic lateral sclerosis corneal confocal microscopy findings background amyotrophic lateral sclerosis als fatal neurodegenerative disorder progressive motor system impairment recent evidence identified extramotor involvement small fiber neuropathy reflecting sensory autonomic disturbances als reported accompany motor damage however noninvasive assessment impairment application disease evaluation als scarce aim evaluate use corneal confocal microscopy ccm noninvasively quantify corneal small fiber neuropathy als explore clinical value assessing disease severity alsmethodssixtysix patients als 64 healthy controls included crosssectional study participants underwent detailed clinical assessments corneal imaging vivo ccm using imagej following parameters quantified corneal nerve length iwl dendritic cell density iwdc inferior whorl region corneal nerve fiber length cnfl nerve fiber density cnfd nerve branch density cnbd dendritic cell density cdc peripheral region disease severity evaluated using recognized scalesresultscorneal nerve lengths iwl cnfl lower dendritic cell densities iwdc cdc higher patients als controls peripheral inferior whorl regions p 005 additionally corneal nerve complexity peripheral region greater patients controls higher cnbd p 0040 lower cnfd p 0011 iwl significantly associated disease severity p 0001 progression p 0002 patients als patients bulbar involvement showed significantly lower iwl p 0014 higher iwdc p 0043 patients without bulbar involvementconclusionsccm quantified significant corneal neuropathy als alterations inferior whorl region closely associated disease severity ccm serve noninvasive objective imaging tool detect corneal small fiber neuropathy clinical evaluation als,0.0
retrospective analysis arterial occlusive events pace trial independent adjudication committee background phase 2 pace ponatinib ph+ cml evaluation trial ponatinib showed robust longterm benefit relapsed philadelphia chromosomepositive ph+ leukemia arterial occlusive events aoes occurred 25 patients based investigator reporting however aoe rates vary depending definitions reporting approach usedmethodsto better understand clinically relevant aoes ponatinib independent cardiovascular adjudication committee reviewed 5year aoe data pace trial according charterdefined process standardized event definitionsresultsa total 449 patients chronic myeloid leukemia cml ph+ acute lymphoblastic leukemia received ponatinib median age 59 y 47 female 93 2 prior tyrosine kinase inhibitors tkis median followup 373 months adjudicated aoe rate 17 lower nonadjudicated rate ie rate adjudication 25 adjudicated aoe 2 patients peripheral arterial occlusive disease 4 exposureadjusted incidence newly occurring adjudicated aoes decreased time patients multiple baseline cardiovascular risk factors higher adjudicated aoe rates without risk factors conclusionsthis independent adjudication study identified lower aoe rates previously reported suggesting earlier overestimation may inaccurately reflect aoe risk ponatinib trial registered clinicaltrialsgov identifier nct01207440 september 23 2010 https clinicaltrialsgov ct2 show nct01207440,0.0
dysregulated b cell differentiation towards antibodysecreting cells neuromyelitis optica spectrum disorder background antiaquaporin 4 aqp4 antibody aqp4ab involved pathogenesis neuromyelitis optica spectrum disorder nmosd however mechanism involved aqp4ab production remains unclearmethodswe analyzed immunophenotypes patients nmosd neuroinflammatory diseases well healthy controls hc using flow cytometry transcriptome analysis b cell subsets obtained nmosd patients hcs performed differentiation capacity b cell subsets antibodysecreting cells analyzedresultsthe frequencies switched memory b smb cells plasmablasts increased nave b cells decreased nmosd patients compared relapsingremitting multiple sclerosis patients hc smb cells nmosd patients enhanced potential differentiate antibodysecreting cells cocultured t peripheral helper cells transcriptome analysis revealed profiles b cell lineage transcription factors nmosd skewed towards antibodysecreting cells il2 signaling upregulated particularly nave b cells nave b cells expressing cd25 receptor il2 increased nmosd patients higher potential differentiate antibodysecreting cells suggesting cd25+ nave b cells committed differentiate antibodysecreting cellsconclusionsto best knowledge first study demonstrate b cells nmosd patients abnormally skewed towards antibodysecreting cells transcriptome level early differentiation phase il2 might participate pathogenic process study indicates cd25+ nave b cells novel candidate precursor antibodysecreting cells autoimmune diseases,0.0
microrna210 regulates metabolic inflammatory status primary human astrocytes background astrocytes numerous glial cell type important roles maintaining homeostasis responding diseases brain astrocyte function subject modulation micrornas mirs short nucleotide strands regulate protein expression posttranscriptional manner understanding mir expression profile astrocytes disease settings provides insight cellular stresses present microenvironment may uncover pathways therapeutic interest methodslasercapture microdissection used isolate human astrocytes surrounding stroke lesions neurological control tissue astrocytic mir expression profiles examined using quantitative reverse transcription polymerase chain reaction rtqpcr primary human fetal astrocytes cultured vitro stress conditions transfection mir mimic used better understand altered levels mir210 affect astrocyte function astrocytic response stress studied using qpcr enzymelinked immunosorbent assays elisas measurement released lactate seahorseresultshere measured mir expression levels astrocytes around human ischemic stroke lesions observed differential expression mir210 chronic stroke astrocytes compared astrocytes neurological control tissue also identified increased expression mir210 mouse white matter tissue around middle cerebral artery occlusion mcao brain lesions aimed understand role mir210 primary human fetal astrocytes developing vitro assay hypoxic metabolic inflammatory stresses combination hypoxic inflammatory stresses observed upregulate mir210 expression transfection mir210mimic 210m increased glycolysis enhanced lactate export promoted antiinflammatory transcriptional translational signature astrocytes additionally 210m transfection resulted decreased expression complement 3 c3 semaphorin 5b sema5b conclusionswe conclude mir210 expression human astrocytes modulated response ischemic stroke disease vitro stress conditions supporting role mir210 astrocytic response disease conditions antiinflammatory proglycolytic impact mir210 astrocytes makes potential candidate research neuroprotective agent,1.0
experiences needs barriers people impairments related usability accessibility digital health solutions levels involvement design process strategies participatory universal design scoping review abstractobjectiveglobally number digital health solutions increasing always designed access utilisation people impairments mind development efforts often included voice requirements people impairments make 15 worlds population despite fact can help ensure broad access utilisation little attention limited inclusion people impairments development digital health solutions results continued reinforced inequalities health services provision people impairments review investigates needs barriers people impairments related use digital health solutions strategies foster user participation access utilisation digital health solutionsmethodsthis scoping review based joanna briggs institute manual five phases 1 identification aim research questions 2 literature search five databases april may 2020 3 literature screening based predetermined inclusion exclusion criteria 4 data extraction 5 reporting resultsresultsthe literature search resulted 5968 sources 25 met inclusion criteria people impairments appreciate digital health solutions designed meet specific impairmentrelated challenges reported needs barriers related technological design varied depending individuals challenges literature reported different types participatory codesign strategies foster access utilisation digital health solutionsconclusionthis scoping review support needs increased awareness among developers design solutions meet peoples needs contexts states health applying universal design strategy including people different types impairments starting idea creation phase digital health solutions throughout development developers can design solutions better accessibility digital health solutions accessible usable tremendous opportunity foster health equity achieve health promotion prevention selfcare turn can contribute closing gap different population groups reduce disparities get available healthcare services,0.0
constitutively active sarm1 variants induce neuropathy enriched als patients background response injury neurons activate program organized axon selfdestruction initiated nad+ hydrolase sarm1 healthy neurons sarm1 autoinhibited single amino acid changes can abolish autoinhibition leading constitutively active sarm1 enzymes promote degeneration expressed cultured neuronsmethodsto investigate whether naturally occurring human variants might disrupt sarm1 autoinhibition potentially contribute risk neurodegenerative disease assayed enzymatic activity 42 rare sarm1 alleles identified among 8507 amyotrophic lateral sclerosis als patients 9671 controls intrathecally injected mice virus expressing sarm1 constructs test capacity alsassociated constitutively active sarm1 variant promote neurodegeneration vivoresultstwelve 42 sarm1 missense variants small inframe deletions assayed exhibit constitutive nadase activity including half unique als patients occur multiple patients 5fold enrichment constitutively active variants among patients compared controls expression constitutively active alsassociated sarm1 alleles cultured dorsal root ganglion drg neurons prodegenerative cytotoxic intrathecal injection aav expressing common sarm1 reference allele innocuous mice construct harboring sarm1v184g constitutively active variant found frequently among als patients causes axon loss motor dysfunction sustained neuroinflammationconclusionsthese results implicate rare hypermorphic sarm1 alleles candidate genetic risk factors als neurodegenerative conditions,0.0
human astrocytes exhibit tumor microenvironment age sexrelated transcriptomic signatures astrocytes critical development function synapses notable species differences human astrocytes commonly used animal models yet unclear whether astrocytic genes involved synaptic function stable exhibit dynamic changes associated disease states age humans barrier understanding human astrocyte biology potential involvement neurological diseases better understand properties human astrocytes acutely purified astrocytes cerebral cortices 40 humans across various ages sexes disease states performed rna sequencing generate transcriptomic profiles astrocytes identified genes associated biological variables found human astrocytes tumorsurrounding regions downregulate genes involved synaptic function sensing signals microenvironment suggesting involvement peritumor astrocytes tumorassociated neural circuit dysfunction aging also found downregulation synaptic regulators upregulation markers cytokine signaling maturation identified changes ionic transport implications calcium signaling addition identified subtle sexual dimorphism human cortical astrocytes implications observed sex differences across many neurological disorders overall genes involved synaptic function exhibit dynamic changes peritumor microenvironment aging data provides powerful new insights human astrocyte biology several biologically relevant states will aid generating novel testable hypotheses homeostatic reactive astrocytes humanssignificance statementastrocytes abundant class cells playing integral roles synapses astrocyte dysfunction implicated variety human neurological diseases yet knowledge astrocytes largely based mouse studies direct knowledge human astrocyte biology remains limited present transcriptomic profiles human cortical astrocytes identified molecular differences associated age sex disease state found peritumor aging astrocytes downregulate genes involved astrocytesynapse interactions data provide necessary insight human astrocyte biology will improve understanding human disease,0.0
reliability gait parameters captured via instrumented walkways systematic review metaanalysis eur j phys rehabil med 2022 jan 5 doi 1023736 s197390872207037x online ahead printabstractintroduction electronic pressuresensitive walkways commonly available solutions quantitatively assess gait parameters clinical research purposes many studies evaluated measurement properties different conditions variable findings order informed current evidence reliability optimal clinical scientific decision making systematic review provided quantitative synthesis testretest reliability minimal detectable change captured gait parameters across different test conditions single cognitive dualtask conditions population groupsevidence acquisition literature search conducted pubmed embase scopus november 2021 identify articles examined testretest reliability properties gait parameters captured pressuresensitive walkways gait speed cadence stride length time double support time base support adult healthy individuals patients methodological quality rated using consensusbased standards selection health measurement instruments checklist data metaanalyzed intraclass correlation coefficient examine testretest relative reliability quantitative synthesis performed absolute reliability examined weighted average minimal detectable change valuesevidence synthesis total 44 studies included systematic review methodological quality adequate half included studies main finding pressuresensitive walkways reliable tools objective assessment spatial temporal gait parameters singleand cognitive dualtask conditions despite exceptions review identified intraclass correlation coefficient higher 075 minimal detectable change lower 30 demonstrating satisfactory relative absolute reliability examined populations healthy adults elderly patients cognitive impairment spinocerebellar ataxia type 14 huntingtons disease multiple sclerosis parkinsons disease rheumatoid arthritis spinal cord injury stroke vestibular dysfunction conclusions current evidence suggested despite different populations testing protocols used included studies testretest reliability examined gait parameters acceptable single cognitive dualtask conditions highquality studies powered sample sizes needed examine reliability findings currently understudied unexplored pathologies test conditionspmid34985239 doi1023736 s197390872207037x,0.0
hyponatremia tip iceberg late diagnosis tuberous sclerosis associated lymphangioleiomyomatosis cureus 2021 dec 3 13 12 e20131 doi 107759 cureus20131 ecollection 2021 decabstracttuberous sclerosis ts rare autosomal dominant multisystem genetic disease causes multiple benign tumors brain vital organs rarely can associated lymphangioleiomyomatosis lma characterized proliferation immature smooth muscle cells walls airways venules lymphatic vessels lung present case 44yearold intellectually disabled woman history marked polydipsia presented emergency department persistent vomiting hemodynamically stable fever analytical study showed severe symptomatic hyponatremia physical examination multiple skin lesions compatible angiofibromas noted diagnosis ts made confirmed genetic study multiorgan study documented presence multiple cystic images lung parenchyma associated lma aim case report highlight importance targeting cutaneous lesions rapid diagnosis pathology identify etiology severe symptomatic ionic disorder referral multidisciplinary teampmid34984158 pmcpmc8720458 doi107759 cureus20131,0.0
patientreported outcome severity emotional salience network disruption multiple sclerosis brain imaging behav 2022 jan 5 doi 101007 s11682021006145 online ahead printabstractbackground overall burden white matter damage associated increased selfreport fatigue severity people multiple sclerosis however paradoxically opposite association reported white matter damage tracts specific subnetworks including amygdala temporal pole insula based neuroanatomical principles data literature hypothesized results might indicative broader relationship damage subnetworks impaired recognition negative emotional salience central patientreported outcomesobjective examined whether damage previouslyidentified subnetworks also associated lower selfreport depressive symptoms something may decreased individuals impaired recognition negative emotional salience patient characteristics also exploredmethods cohort 137 people multiple sclerosis measured locationspecific network white matter tract damage proposed negative emotional salience network along selfreport severity depressive symptoms cognitive problems personality characteristics objective cognitive performance physical disability applied regression analyses accounting lesion burden explore relationship damage proposed negative emotional salience network factorsresults found disruption within negative emotional salience network associated lower selfreport depressive symptoms 0277 p 0036 cognitive complaints r 0196 p 0024 personality trait neuroticism r 0179 p 0042 contrast damage within network significantly associated objective cognitive processing speed personality trait openness physical disabilityconclusion identified network may generalizable network corresponds recognition negative emotional salience objective factors processing speed physical disability damage network may paradoxically buffer negative emotional perception symptom severity central patientreported outcomespmid34985619 doi101007 s11682021006145,0.0
long noncoding rna acta2as1 inhibits cisplatin resistance nonsmall cell lung cancer cells inhibiting autophagy suppressing tsc2 cell cycle 2022 jan 5111 doi 101080 1538410120212020433 online ahead printabstractlong noncoding rna lncrna acta2as1 reported play important role progression multiple human malignancies article aims explore role acta2as1 cisplatin resistance nonsmall cell lung cancer nsclc rtqpcr performed investigate expression acta2as1 cisplatinresistant nsclc cell lines western blot used investigate effects acta2as1 autophagyrelated protein expression rip assay rna pull used analyze combination acta2as1 enhancer zeste homolog 2 ezh2 chip used analyze combination tuberous sclerosis complex2 tsc2 gene promoter lys27 histone h3 h3k27me3 study acta2as1 downregulated cisplatinresistant nsclc cell lines acta2as1 negatively regulated cell viability positively regulated cell apoptosis cisplatinresistant nsclc cell lines furthermore results demonstrated acta2as1 promoted cisplatinresistant nsclc cells apoptosis inhibiting autophagy regulation acta2as1 cisplatinresistant nsclc cell autophagy reversed tsc2 increasing importantly results displayed acta2as1 bound ezh2 tsc2 gene promoter combined h3k27me3 inhibition acta2as1 tsc2 expression recused ezh2 silencing conclusion acta2as1 inhibited cisplatin resistances nsclc cell lines suppressing tsc2 expressing recruiting ezh2 tsc2 gene promoterpmid34985374 doi101080 1538410120212020433,0.0
predominant monomorphism rit2 gpm6b exceptionally long ga blocks human enriched divergent alleles disease compartment genetica 2022 jan 5 doi 101007 s10709021001435 online ahead printabstractacross human proteincoding genes human neuronspecific genes rit2 gpm6b contain two longest ga short tandem repeats strs 11 9repeats respectively length ranges functional result gene expression alteration sequenced rit2 gpm6b strs 600 human subjects consisting lateonset neurocognitive disorder n 200 multiple sclerosis n 200 controls n 200 furthermore selected two large human databases including generalpopulationbased gnomad https gnomadbroadinstituteorg mainly diseasephenotypearchiving database topmed https wwwnhlbiwgsorg compare allele frequencies general populations vs disease compartment rit2 gpm6b garepeats monomorphic human subjects studied lengths 11 9repeats respectively predominantly humanspecific formula exception included 9 11 genotype rit2 gastr isolate case female multiple sclerosis exceedingly rare alleles two ga repeats significantly enriched topmed vs gnomad report prime instances predominant monomorphism specific lengths strs human possible enrichment rare divergent alleles disease phenotype compartment strs attended high polymorphic nature str monomorphism underappreciated feature may link natural selection diseasepmid34984576 doi101007 s10709021001435,0.0
reduction cognitive processing speed surrounding multiple sclerosis relapse ann neurol 2022 jan 4 doi 101002 ana26301 online ahead printabstractobjective explore longitudinal relationship multiple sclerosis ms relapses information processing efficiency among persons relapsingremitting msmethods swedish nationwide cohort study persons incident relapsingremitting ms 20012019 relapse information symbol digit modalities test sdmt scores obtained swedish ms registry followup categorized two periods based relapse status relapse 90 days prerelapse 730 days postrelapse subdivided 10 periods remission linear mixed models compared sdmt scores relapse periods sdmt scores recorded remission reference results reported coefficients 95 confidence intervals ci adjusted age sex sdmt type written vs oral timevarying diseasemodifying therapy exposure sequence sdmtresults mean sd followup 107 43 years 31 529 distinct sdmts recorded among 3877 persons ms significant decline information processing efficiency lasted 30 days prerelapse 550 days postrelapse largest decline occurring 030 days postrelapse coefficient400 95ci 461 339 relative period remissioninterpretation found evidence cognitive change one month prior relapse onset reduction sdmt lasted 15 years clinically significant three months postrelapse results suggest effects relapse cognition longer previously thought highlight importance reducing relapse rates potential means preserving cognitive function article protected copyright rights reservedpmid34984719 doi101002 ana26301,0.0
results multicenter randomized doubleblind placebocontrolled study repository corticotropin injection multiple sclerosis relapse adequately respond corticosteroids cns neurosci ther 2022 jan 4 doi 101111 cns13789 online ahead printabstractintroduction 2035 multiple sclerosis ms patients fail respond highdose corticosteroids relapse repository corticotropin injection rci acthar gel naturally sourced complex mixture adrenocorticotropic hormone analogs pituitary peptides antiinflammatory immunomodulatory effectsaims study objective determine efficacy safety rci patients ms relapse inadequately responded corticosteroids multicenter doubleblind placebocontrolled study nonresponders highdose corticosteroids randomized receive rci 80 u placebo daily 14 days assessments included improvements expanded disability status scale edss multiple sclerosis impact scale msis29 clinical global impression improvement cgii adverse events aes results eighteen patients received rci 17 received placebo greater proportion edss responders observed rci group day 7 21 42 compared placebo group qualitative cgii showed patients receiving rci much improved much improved placebo meaningful differences observed treatment groups msis29 serious aes deaths reportedconclusion rci safe effective ms relapse patients respond highdose corticosteroidspmid34984839 doi101111 cns13789,0.0
determinants covid19related lethality multiple sclerosis metaregression observational studies j neurol 2022 jan 4 doi 101007 s00415021109516 online ahead printabstractobjective identify risk factors increased lethality covid19 patients multiple sclerosis ms methods searched scientific databases identify cohort studies number deaths patients ms fitted inversevariance weighted metaregressions randomeffects models identify potential moderators determinants covid19related lethality outcome results independent screening 18 articles satisfied eligibility criteria data collected antisarscov2 vaccination available 5 634 patients 111 died yielding pooled death rate 197 95 confidence intervals 161233 substantial heterogeneity included studies q17 669 p 0001 i2 775 relevant publication bias p 0085 higher lethality observed studies including older patients 080 p 0025 studies higher proportions patients comorbidity 017 p 0046 progressive disease course 015 p 0027 current treatment anticd20 agents 018 p 0001 otherwise higher proportions patients treated interferon beta 016 p 0001 teriflunomide 011 p 0035 associated lower lethality estimates change even multivariable metaregressions including adjustment variables leaveoneout sensitivity analysesconclusion except age comorbidities risk factors common general population identified msspecific determinants influencing lethality covid19 findings suggest implementation risk mitigation plan patients progressive ms treated anticd20 agentspmid34984514 doi101007 s00415021109516,0.0
comprehensive review role gut microbiome human neurological disorders clin microbiol rev 2022 jan 5e0033820 doi 101128 cmr0033820 online ahead printabstractthe human body full extensive number commensal microbes consisting bacteria viruses fungi collectively termed human microbiome initial acquisition microbiota occurs external maternal environments vast majority colonize gastrointestinal tract git microbial communities play central role maturation development immune system central nervous system git system also responsible essential metabolic pathways various factors including host genetic predisposition environmental factors lifestyle diet antibiotic nonantibiotic drug use etc affect composition gut microbiota recent publications highlighted imbalance gut microflora known dysbiosis associated onset progression neurological disorders moreover characterization microbiomehost cross talk pathways provides insight novel therapeutic strategies novel preclinical clinical research interventions related gut microbiome treating neurological conditions including autism spectrum disorders parkinsons disease schizophrenia multiple sclerosis alzheimers disease epilepsy stroke hold significant promise review aims present comprehensive overview potential involvement human gut microbiome pathogenesis neurological disorders particular emphasis potential microbebased therapies diagnostic microbial biomarkers review also discusses potential health benefits administration probiotics prebiotics postbiotics synbiotics fecal microbiota transplantation neurological disorderspmid34985325 doi101128 cmr0033820,0.0
constraintinduced movement therapy upper limb rehabilitation multiple sclerosis eur j phys rehabil med 2022 jan 5 doi 1023736 s1973908722070253 online ahead printno abstractpmid34985238 doi1023736 s1973908722070253,0.0
cxcl4 drives fibrosis promoting several key cellular molecular processes cell rep 2022 jan 4 38 1 110189 doi 101016 jcelrep2021110189abstractfibrosis major cause mortality worldwide characterized myofibroblast activation excessive extracellular matrix deposition systemic sclerosis prototypic fibrotic disease cxcl4 increased strongly correlates skin lung fibrosis aim elucidate role cxcl4 fibrosis development cxcl4 levels increased multiple inflammatory fibrotic mouse models using cxcl4deficient mice demonstrate essential role cxcl4 promoting fibrotic events skin lungs heart overexpressing human cxcl4 mice aggravates whereas blocking cxcl4 reduces bleomycininduced fibrosis singlecell ligandreceptor analysis predicts cxcl4 affect endothelial cells fibroblasts vitro confirm cxcl4 directly induces myofibroblast differentiation collagen synthesis different precursor cells including endothelial cells stimulating endothelialtomesenchymal transition findings identify pivotal role cxcl4 fibrosis substantiating potential role neutralizing cxcl4 therapeutic strategypmid34986347 doi101016 jcelrep2021110189,0.0
liraglutide attenuate central nervous inflammation demyelination ampk pyroptosisrelated nlrp3 pathway cns neurosci ther 2022 jan 5 doi 101111 cns13791 online ahead printabstractaims multiple sclerosis ms still maintains increasing prevalence poor prognosis glucagonlike peptide1 receptor glp1r agonists show excellent neuroprotective capacities recently thus aim evaluate whether glp1r agonist liraglutide lira ameliorate central nervous system demyelination inflammationmethods therapeutic effect lira tested experimental autoimmune encephalitis eae vivo microglia cell line bv2 vitroresults lira administration ameliorate disease score eae mice delay disease onset ameliorate pathological demyelination inflammation score lumbar spinal cord reduce pathogenic t helper cell transcription spleen restore phosphorylated adenosine monophosphateactivated protein kinase pampk level autophagy level inhibit pyroptosisrelated nlr family pyrin domaincontaining protein 3 nlrp3 pathway lumbar spinal cord additionally cell viability test lactate dehydrogenase release test dead live cell staining test bv2 cells showed lira salvage bv2 nigericininduced pyroptosis significantlyconclusion lira antiinflammation antidemyelination effect eae mice protective effect lira eae model may related regulation pampk pathway autophagy nlrp3 pathway however lira treatment significantly inhibit pyroptosis bv2 cells vitro study provides lira potential candidate multiple sclerosis treatmentpmid34985189 doi101111 cns13791,1.0
susac#39 s syndrome diagnostic difficulties neurological point view neurol neurochir pol 2022 jan 5 doi 105603 pjnnsa20210082 online ahead printabstractsusacs syndrome rare microangiopathy affecting small vessels retina inner ear brain characterised triad symptoms encephalopathy visual defects sensorineural hearing loss disease probably caused autoimmune process diagnosis based typical symptoms brain mri importantly fluorescein angiography important distinguish susacs syndrome multiple sclerosis migraine aura misdiagnosis leads wrong treatment date detailed guidelines treatment susacs syndrome developed immunosuppression seems effective must remembered early aggressive treatment crucial delays diagnosis result treatment implementation worsen prognosispmid34985117 doi105603 pjnnsa20210082,0.0
dicam promotes th17 lymphocyte trafficking across bloodbrain barrier autoimmune neuroinflammation sci transl med 2022 jan 5 14 626 eabj0473 doi 101126 scitranslmedabj0473 epub 2022 jan 5abstract figure see text pmid34985970 doi101126 scitranslmedabj0473,0.0
ponesimod inhibits astrocytemediated neuroinflammation protects cingulum demyelination via s1p1selective modulation abstractponesimod sphingosine 1phosphate s1p receptor s1pr modulator recently approved treating relapsing forms multiple sclerosis ms three fdaapproved s1pr modulators msfingolimod siponimod ozanimodshare peripheral immunological effects via common s1p1 interactions yet ponesimod may access distinct central nervous system cns mechanisms selectivity s1p1 receptor ponesimod examined s1pr internalization binding human astrocyte signaling singlecell rnaseq scrnaseq gene expression vivo using murine cuprizonemediated demyelination studies confirmed ponesimods selectivity s1p1 without comparable engagement s1pr subtypes s1p2 3 4 5 ponesimod showed pharmacological properties acute agonism followed chronic functional antagonism s1p1 major locus s1p1 expression cns astrocytes scrnaseq primary human astrocytes exposed ponesimod identified gene ontology relationship reduced neuroinflammation reduction known astrocyte diseaserelated genes including immediate early astrocytes strongly associated disease progression ms animal models remarkably ponesimod prevented cuprizoneinduced demyelination selectively cingulum corpus callosum data support cns activities ponesimod s1p1 including protective likely selective effects demyelination major connection pathway brain limbic fibers cingulum lesions associated several neurologic impairments including ms fatigue,1.0
grey systems management demand palliative care services poland background concept care people critical even terminal health condition last stage life become mission palliative care facilities therefore life sick patient poses number challenges health care services make sure medical services tailored trajectory disease well various needs preferences resources patients familiesmethodshealth systems financed public funds need adopt new methods management meet high arising demand longterm care several ways assessing demand longterm care services method recommended author presented detail paper one relying grey systems enables estimation forecasting models finally actual forecasts number potential future patientsresultsgst can used make predictions future behaviour system article aims present possibility using firstorder grey model gm 1 1 predicting number patients palliative care facilities poland analysis covers data 2014 2019 whereas prediction number patients additionally formulated 2020conclusionshealth systems particularly publicly funded ones characterised certain kind incompleteness uncertainty data structure behaviour individual components eg potential patients payers present study aims prove simple effective grey systems models decisionmaking process,0.0
brief electrical nerve stimulation enhances intrinsic repair capacity focally demyelinated central nervous system neural regen res 2022 may 17 5 10421050 doi 104103 16735374324848abstractour lab shown brief electrical nerve stimulation es dramatic impact remyelination lysophosphatidyl choline lpc induced focally demyelinated rat peripheral nerves also inducing axonprotective phenotype shifting macrophages predominantly proinflammatory toward prorepair phenotype whether potential exists central nervous system known thus proof principle studies peripheral nerve demyelination es model adapted central nervous system whereby unilateral focal lpcinduced demyelination dorsal column lumbar enlargement sciatic nerve afferents enter created subsequent ipsilateral sciatic nerve es results increased neural activity demyelinated axons data reveal robust focal demyelination 7 days postlpc injection delivery 1hour es 7 days postlpc polarizes macrophages microglia toward prorepair phenotype examined 14 days postlpc results smaller lpcassociated regions inflammation compared nonstimulated controls results significantly cells oligodendroglial lineage demyelinated region elevates myelin basic protein levels shifts paranodal protein caspr along demyelinated axons restricted distribution consistent reformation paranodes nodes ranvier es also significantly enhanced levels phosphorylated neurofilaments detected zones demyelination shown confer axon protection collectively findings support strategies increase neural activity brief electrical stimulation can beneficial promoting intrinsic repair following focal demyelinating insults demyelinating diseases multiple sclerosis animal procedures performed approved university saskatchewans animal research ethics board protocol# 20090087 last approval date november 5 2020 pmid34558531 doi104103 16735374324848,1.0
medicinal chemistry updates novel hdacs inhibitors 2020 present eur j med chem 2021 oct 22 227113946 doi 101016 jejmech2021113946 online ahead printabstractepigentic enzymes histone deacetylases hdacs catalyze removal acetyl groups nacetylated lysine residues various protein substrates including histone nonhistone proteins different hdacs distinct biological functions recruited specific regions genome due important biological functions hdacs validated clinics anticancer therapy explored potential treatment several diseases alzheimer disease ad metabolic disease viral infection multiple sclerosis etc besides five approved drugs thirty hdacs inhibitors currently investigated clinical trials centering advances drug discovery programs field since 2020 review discusses hdacs inhibitors aspects structurebased rational design isoform selectivity pharmacology toxicology compounds interest hope provide medicinal chemistry community uptodate information accelerate drug discovery programs areapmid34775332 doi101016 jejmech2021113946,0.0
myocardial infarction stroke risks multiple sclerosis patients twosample mendelian randomization study abstractobservational studies indicated multiple sclerosis ms patients may higher risk myocardial infarction mi stroke general population whereas previously reported findings inconsistent using twosample mendelian randomization mr analysis genetic data largescale genomewide association studies international multiple sclerosis genetics consortium containing 14 498 ms cases coronary artery disease genome wide replication metaanalysis plus coronary artery disease genetics consortium containing 43 676 mi cases 40 585 stroke cases found ms causally associated increased risk mi or103 95ci 100106 p00243 directionally consistent weighted median mregger mrpresso methods causal association ms stroke observed or101 95ci 099104 p02974 therefore timelier effective measures conducted among ms patients decrease burden diseases,0.0
correlations hippocampal functional connectivity structural changes clinical data patients relapsingremitting multiple sclerosis casecontrol study using multimodal magnetic resonance imaging neural regen res 2022 may 17 5 11151124 doi 104103 16735374324855abstractmultiple sclerosis associated structural functional brain alterations leading cognitive impairments across multiple domains including attention memory speed information processing hippocampus brain important structure involved memory undergoes microstructural changes early stage multiple sclerosis study analyzed hippocampal function structure patients relapsingremitting multiple sclerosis explored correlations functional connectivity hippocampus whole brain changes local brain function microstructure cognitive function rest retrospectively analyzed data 20 relapsingremitting multiple sclerosis patients admitted department neurology chinajapan union hospital jilin university china april 2015 november 2019 sixteen healthy volunteers recruited healthy control group participants evaluated using scale extended disability status montreal cognitive assessment within 1 week head diffusion tensor imaging functional magnetic resonance imaging compared healthy control group patients relapsingremitting multiple sclerosis lower montreal cognitive assessment scores regions simultaneously enhanced attenuated wholebrain functional connectivity local functional connectivity bilateral hippocampus hippocampal diffusion tensor imaging data showed compared healthy control group patients relapsingremitting multiple sclerosis lower hippocampal fractional anisotropy values higher mean diffusivity values suggesting abnormal hippocampal structure left hippocampus wholebrain functional connectivity negatively correlated montreal cognitive assessment score r 0698 p 0025 wholebrain functional connectivity right hippocampus negatively correlated extended disability status scale score r 0649 p 0042 mean diffusivity value left hippocampus negatively correlated montreal cognitive assessment score r 0729 p 0017 positively correlated extended disability status scale score r 0653 p 0041 right hippocampal mean diffusivity value positively correlated extended disability status scale score r 0684 p 0029 data suggest functional connectivity presence structural abnormalities hippocampus patients relapseremission multiple sclerosis correlated degree cognitive function extent disability study approved ethics committee chinajapan union hospital jilin university china approval 201702202 february 22 2017pmid34558540 doi104103 16735374324855,0.0
acazicolcept alpn101 dual icos#x2f cd28 antagonist demonstrates efficacy systemic sclerosis preclinical mouse models background uncontrolled immune response t cell activation key role pathogenesis systemic sclerosis ssc disorder characterized generalized fibrosis affecting particularly lungs skin costimulatory molecules key players immune activation recent evidence supports role cd28 icos development fibrosis herein investigated efficacy acazicolcept alpn101 dual icos cd28 antagonist two complementary sscrelated mouse models recapitulating skin fibrosis interstitial lung disease pulmonary hypertensionmethodsexpression circulating soluble icos skinexpressed icos investigated ssc patients thereafter acazicolcept evaluated hypochlorous acid hocl induced dermal fibrosis mouse model fra2 transgenic tg mouse model model mice received 400 g acazicolcept molarmatched dose fc control protein twice week 6 weeks 6 weeks skin lung evaluatedresultsicos significantly increased sera ssc patients ssc skin biopsies compared samples healthy controls similar body weight changes observed fc control acazicolcept groups hocl fra2 tg mice suggesting good tolerance acazicolcept treatment mice challenged hocl acazicolcept induced significant decrease dermal thickness collagen content myofibroblast number inflammatory infiltrates characterized b cells t cells neutrophils macrophages fra2 tg mouse model acazicolcept treatment reduced lung collagen content fibrillar collagen histological fibrosis score right ventricular systolic pressure rvsp reduction frequency cd4+ t effector memory cells increase percentage cd4+ t nave cells spleen lung acazicolcepttreated fra2 tg mice observed compared fc controltreated fra2 tg mice moreover acazicolcept reduced cd69 pd1 expression cd4+ t cells spleen lung target engagement acazicolcept demonstrated blockade cd28 icos detection flow cytometry treated miceconclusionsour results confirm importance costimulatory molecules inflammatorydriven fibrosis data highlight key role icos cd28 ssc using complementary models demonstrated dual icos cd28 blockade acazicolcept decreased dermal pulmonary fibrosis alleviated pulmonary hypertension results pave way subsequent research icos cd28targeted therapies,0.0
leukoencephalopathy brain calcifications cysts labrune syndrome case report diagnosis management rare neurological disease background leukoencephalopathy brain calcifications cysts lcc also known labrune syndrome rare genetic microangiopathy caused biallelic mutations snord118 mechanisms lossoffunction mutations snord118 lead phenotype leukoencephalopathy calcifications intracranial cysts unknowncase presentationwe present histopathology 36yearold woman ataxia neuroimaging findings diffuse white matter abnormalities cerebral calcifications parenchymal cysts diagnosis lcc confirmed genetic testing biopsy frontal white matter revealed microangiopathy small vessel occlusion sclerosis associated axonal loss within white matterconclusionsthese findings support white matter changes seen lcc arise consequence ischemia rather demyelination,1.0
apoptotic protease activating factor1 gene microrna484 possible interplay relapsing remitting multiple sclerosis abstractbackground emerging evidence suggests dysregulated apoptosis might implicated pathogenesis multiple sclerosis ms aim current study evaluate expression apoptotic protease activating factor1 apaf1 mrna potential regulator mir484 relapsing remitting ms patients rrms investigate role potential disease biomarkersmethods bioinformatic analysis conducted revealed mir484 involvement regulation apaf1 gene expression reverse transcriptionquantitative realtime pcr rtqpcr performed detect expression levels apaf1 mir484 peripheral blood mononuclear cells pbmcs 34 rrms patients recruited ms clinic kasr al ainy hospital faculty medicineegypt 34 healthy controlsresults apaf1 mrna significantly downregulated patients median rq54 p 001 whereas mir484 expression upregulated compared controls median rq208 sensitivity specificity apaf1 mir484 diagnose ms 882 867 853 765 respectivelyconclusion apaf1 mir484 play role potential ms diagnostic biomarkers however absence control group patients inflammatory diseases study warrants research corroborate findings,0.0
extensive brain pathologic alterations detected 70t mr spectroscopic imaging associated disability multiple sclerosis radiology 2022 jan 4210614 doi 101148 radiol210614 online ahead printabstractbackground mr spectroscopic imaging mrsi allows vivo assessment brain metabolism special interest multiple sclerosis ms morphologic mri depict major parts disease activity purpose evaluate ability 70t mrsi depict visualize pathologic alterations normalappearing white matter nawm cortical gray matter cgm participants ms investigate relation disability materials methods freeinduction decay mrsi performed 70 t participants ms age sexmatched healthy controls recruited prospectively january 2016 december 2017 metabolic ratios obtained white matter lesions nawm cgm regions subgroup analysis msrelated disability based expanded disability status scale edss scores performed using analysis covariance partial correlations applied explore associations metabolic ratios disability results sixtyfive participants ms mean age standard deviation 34 years 9 34 women 20 age sexmatched healthy controls mean age 32 years 7 11 women evaluated higher signal intensity myoinositol mi without reduced signal intensity nacetylaspartate naa visible metabolic images nawm participants ms higher ratio mi total creatine tcr observed nawm centrum semiovale ms subgroups including participants without disability marginal mean standard error healthy controls 078 004 edss 01 086 003 p 02 edss 153 095 004 p 001 edss 35 094 004 p 001 lower ratio naa tcr found ms subgroups disabilities nawm marginal mean standard error healthy controls 146 004 edss 153 133 003 p 03 edss 35 130 004 p 01 cgm marginal mean standard error healthy controls 142 005 edss 35 123 005 p 006 mi naa correlated edss nawm centrum semiovale r 047 p 001 parietal nawm r 043 p 002 frontal nawm r 034 p 01 frontal cgm r 037 p 004 conclusion mr spectroscopic imaging 70 t allowed vivo visualization multiple sclerosis pathologic findings visible t1 t2weighted mri metabolic abnormalities normalappearing white matter cortical gray matter associated disability rsna 2022 online supplemental material available article see also editorial barker issuepmid34981978 doi101148 radiol210614,0.0
intelligibility across reading passage effect dysarthria cued speaking styles j speech lang pathol 2022 jan 4119 doi 101044 2021_ajslp2100151 online ahead printabstractobjective reading passage loud commonly used task perceptual assessment dysarthria extent perceptual characteristics remain unchanged stable time course passage largely unknown study investigated crowdsourced visual analogue scale vas judgments intelligibility across reading passage function cued speaking styles commonly used treatment maximize intelligibilitypatients method hunter passage read aloud habitual slow loud clear speaking styles 16 speakers parkinsons disease pd 30 speakers multiple sclerosis ms 32 control speakers vas judgments intelligibility three fragments representing beginning middle end reading passage obtained 540 crowdsourced online listenersresults overall passage intelligibility reduced two clinical groups relative control group speaker groups exhibited intelligibility variation across reading passage trends increased intelligibility toward end reading passage control speakers speakers pd patterns intelligibility variation across passage reading differ speaking style ms group intelligibility variation across passage dependent speaking styleconclusions presence intelligibility variation within reading passage warrants careful selection speech materials research clinical practice results indicate crowdsourced vas rating paradigm useful document intelligibility reading passage different cued speaking styles commonly used treatment dysarthriapmid34982941 doi101044 2021_ajslp2100151,0.0
analysis microrna144 expression profile patients multiple sclerosis comparison healthy individuals rep biochem mol biol 2021 oct 10 3 396401 doi 1052547 rbmb103396abstractbackground etiology multiple sclerosis nonclarified seems environmental factors impact epigenetic disease micrornas mir epigenetic factors one important factors nongenetically neurodegenerative diseases found mir144 plays main role regulation many processes central nervous system aimed investigation mir144 expression alteration multiple sclerosis ms patientsmethods study 32 healthy 32 ms patients blood sample analyzed quantitative realtime pcr method obtained data analyzed rest 2009 softwareresults analysis realtime pcr data revealed mir144 increase significantly ms patients compared healthy controlsconclusion increase mir144 expression ms patients obvious mir144 can used biomarker ms help early diagnosis treatment diseasepmid34981016 pmcpmc8718777 doi1052547 rbmb103396,0.0
targeting neuroinflammation intranasal delivery nanoparticles neurological diseases comprehensive review naunyn schmiedebergs arch pharmacol 2022 jan 4 doi 101007 s0021002102196x online ahead printabstractneuroinflammation nif plays essential role pathology neurological disorders like parkinsons disease alzheimers disease multiple sclerosis epilepsy despite progress drug discovery development new drugs drug delivery central nervous system cns still represents challenge due presence bloodbrain barrier bbb targeting nif may require adequate amount drug cross bbb recently intranasal drug administration attracted increasing attention reliable method cross bbb treat neurological disorders hand using optimized nanoparticles may improve delivery limitations increase mucoadhesive properties prevent drug degradation nps can carry deliver drugs cns bypassing bbb review described briefly nif pathologic feature cns diseases potential treatment possibilities transfer nploaded drugs will enhance establishment efficient nanoformulations delivery systemspmid34982185 doi101007 s0021002102196x,0.0
acute subacute spinal cord infarction mimicking acute multiple sclerosis usefulness diffusionweighted mri diagnosis curr med imaging 2022 jan 3 doi 102174 1573405618666220103105910 online ahead printabstractbackground spinal cord infarction sci difficult diagnose rarity unknown etiology unestablished diagnostic criteria additionally timeline sci studied detail studies using diffusionweighted image dwi sequences spine small target population previously conductedcase study 56yearold male underlying arrhythmia suddenly developed visual field defects right side pain left upper extremity tingling sensation left hand brain magnetic resonance imaging mri revealed acute subacute stages multifocal brain infarction additional cervical spinal mri showed atypical mri findings sci considered late acute early subacute phase similar seen acute phase multiple sclerosis ms additional dwi revealed restricted diffusion findings inferred patients sci occurred time multifocal brain infarctions caused atrial fibrillationconclusion dwi sequence spine mri helpful diagnosis acute subacute phase sci differentiating acute mspmid34979892 doi102174 1573405618666220103105910,0.0
multiple sclerosisminimizing errors radiological diagnosis neurol india 2021 novdec 69 6 15391546 doi 104103 00283886333497abstractbackground multiple sclerosis chronic demyelinating disorder myriad imaging clinical features overlap number neurological conditions incorrect diagnosis poses significant risk patients may lead delays management increased morbidity also adds financial costobjective aim study highlight strategies efficient differentiation multiple sclerosis diseases may masquerade ms clinicoradiologicallymaterial methods systematic literature review conducted online databases including pubmed medline relevant publications radiological aspects multiple sclerosis white matter diseases mimickers multiple sclerosis included analysisresults common mimickers ms include small vessel disease acute disseminated encephalomyelitis neuromyelitis optica antimog encephalomyelitis vasculitis cadasil contrastenhanced mri study performed using ms protocol high strength mri system evaluated following structured protocol along clinical correlation effective differentiating ms mimickersconclusions contrastenhanced mri performed high strength scanner using ms protocol structured protocol evaluation along better collaboration radiologists clinicians may help minimizing errors diagnosis multiple sclerosispmid34979638 doi104103 00283886333497,1.0
longterm realworld effectiveness safety fingolimod 5years germany j neurol 2022 jan 4 doi 101007 s0041502110931w online ahead printabstractobjective evaluate 5year realworld benefitrisk profile fingolimod patients relapsingremitting ms rrms germanymethods postauthorization noninterventional german safety study gilenya pangaea noninterventional realworld study prospectively assess effectiveness safety fingolimod routine clinical practice germany followup period comprised 5 years patients included diagnosed rrms prescribed fingolimod part clinical routine exclusion criteria except contraindications fingolimod defined european label effectiveness safety analysis set comprised 4032 4067 rrms patients respectivelyresults time 5year followup pangaea 6657 patients still continued fingolimod therapy annualized relapse rates decreased baseline 15 115 042 0734 year 1 021 0483 year 5 disability status remained stable demonstrated expanded disability status scale mean change baseline 01 251 decrease multiple sclerosis severity score 51 259 baseline 39 231 60months followup percentage patients change clinical global impression scale 60months followup 7811 adverse events ae occurring 7504 patients line known safety profile fingolimod mostly nonserious ae 3362 nonserious adverse drug reactions 5059 serious ae 498 serious adr 1082 conclusions pangaea demonstrated sustained beneficial effectiveness safety fingolimod longterm realworld treatment patients rrmspmid34982201 doi101007 s0041502110931w,0.0
acute disseminated encephalomyelitis psychiatric presentation rare diagnosis innov clin neurosci 2021 julsep 18 79 4446abstractacute disseminated encephalomyelitis adem autoimmune inflammatory disease central nervous system characterized widespread demyelination predominantly involving white matter brain spinal cord often caused viral infection vaccination clinical features include acute encephalopathy multifocal neurologic signs deficits children can present psychosis depression abnormal behavior might mimic dissociative disorder report involves similar rare case 14yearold female patient presented fluctuating weakness body slurring speech tremor loss responsiveness abnormal behavior fever waned diagnosis dissociative disorder considered absence neurological findings ongoing significant stressor eventually turned adem confirmed late neurological manifestations radiological evaluation neuroimaging also revealed differences multiple sclerosispmid34980993 pmcpmc8667702,1.0
effect activation core muscles tremor patient multiple sclerosis neurol india 2021 novdec 69 6 17981801 doi 104103 00283886333519abstractbackground trunk stabilization important providing postural control extremity movements maintained muscles called coreobjective aim report demonstrate effect core muscles contraction upper extremity tremormaterials methods 22yearold multiple sclerosis patient right extremity ataxia included report scale assessment rating ataxia sara expanded disability status scale edss accelerometric tremorogram purdue peg board test ppbt performed assessments made without core muscles contractionresults total score sara decreased 16 14 due reduction dysmetria tremor scores tremor amplitude decreased contraction tremorogram 1st position tremor amplitude changed 146 contraction 183 contraction position 2 6 hz tremor disappeared contraction ppbt ataxic extremity performance increased 5 7conclusion contraction core muscles reduced postural tremor improved upper extremity performance considered planning training program ataxic ms patientspmid34979692 doi104103 00283886333519,0.0
brain pathology multiple sclerosis highfieldstrength mr spectroscopic imaging radiology 2022 jan 4212026 doi 101148 radiol212026 online ahead printno abstractpmid34981980 doi101148 radiol212026,0.0
ocrelizumab versus fingolimod natalizumab cessation multiple sclerosis observational study j neurol 2022 jan 4 doi 101007 s00415021109507 online ahead printabstractbackground exit strategy natalizumab cessation multiple sclerosis ms crucial point risk disease reactivation high period objective observational study compare ocrelizumab fingolimod natalizumab cessation patients relapsingremitting multiple sclerosis rrms methods rrms patients starting fingolimod ocrelizumab within 6 weeks natalizumab cessation included primary endpoint annualized relapse rate arr 1 yearresults included 54 patients receiving fingolimod 48 patients receiving ocrelizumab natalizumab cessation multivariate analysis arr 1 year significantly lower ocrelizumab group fingolimod group 012 039 versus 041 071 p 0026 ie 707 lower relapse rate cumulative probability relapses 1 year 315 17 54 patients fingolimod 104 5 48 patients ocrelizumab corresponding hazard ratio 34 95 confidence interval 1111 p 004 conclusions results suggest ocrelizumab potentially better exit strategy fingolimod natalizumab cessationpmid34982200 doi101007 s00415021109507,0.0
advances use stem cell transplants treatment multiple sclerosis j neurol 2022 jan 4 doi 101007 s00415021109276 online ahead printno abstractpmid34982199 doi101007 s00415021109276,0.0
improving healthcare professional psychological wellbeing neurorehabilitation exploratory study focusing work stress innov clin neurosci 2021 julsep 18 79 2128abstractbackground work stress ws set harmful physical emotional reactions occur demands coming work adequate skills resources needs worker causes physical mental psychological social suffering dysfunction can lead burnout syndromeobjective aim study evaluate ws healthcare professions evaluating effectiveness professional stress prevention program promote reduction wsmethods thirtythree healthcare professionals multiple sclerosis ms rehab ward irccs neurolesi messina italy enrolled study professional stress prevention program based group support activities well individual supportresults baseline found high burnout risk physiotherapists physicians healthcare professionals end meetings found normalization ws higher sense personal realization healthprofessions greater use functional coping strategiesconclusion occupational stressreducing intervention healthcare teams can promote reduction stress anxiety encouraging functional coping strategies face work difficultiespmid34980990 pmcpmc8667696,0.0
quality life patients multiple sclerosis neuromyelitis optica spectrum disorders crosssectional longitudinal analysis abstractbackgroundmultiple sclerosis ms aquaporin4 antibodypositive neuromyelitis optica spectrum disorders nmosd different pathogenic mechanisms negatively affect patients lifetime aimed analyze compare quality life qol patients ms nmosd longitudinal course associated factors two diseasesmethodsbetween june 2018 april 2020 patients ms nmosd visited tertiary hospital prospectively enrolled euroqol5 dimension eq5d utility index low values represent poor qol expanded disability status scale edss hospital anxiety depression scale hads collected enrollment followup 612month interval baseline degree qol determinants analyzed compared ms nmosd groups also analyzed longitudinal alteration eq5d utility indices time factors associated followup qolresultsduring study period 171 patients ms 120 nmosd 51 included median age 46 years median edss score followup duration 25 8 months respectively baseline eq5d utility indices low comparable ms nmosd groups median 086 vs 082 p0823 higher hads total score severe anxiety depression symptoms showed independent significant association baseline eq5d utility index disease groups longitudinally eq5d utility indices remained low although significantly change time group level 50 patients showed longitudinal change eq5d indices disease groups note higher hads total score enrollment independent predictor poor qol follow disease groupsconclusionsthe qol similarly impaired patients ms nmosd remained low followup period higher total scale hads independent risk factor lower qol baseline followup disease conditions suggesting clinicians pay attention anxiety depression patients ms nmosd long term,0.0
administration human derived upper gut commensal prevotella histicola delays onset type 1 diabetes nod mice background type 1 diabetes t1d autoimmune disease increasing prevalence worldwide one contributing factors pathogenesis t1d composition intestinal microbiota demonstrated t1d patients studies demonstrating deficiency levels prevotella isolated strain prevotella histicola duodenal biopsy antiinflammatory properties addition alters development autoimmune diseases mouse models therefore hypothesis oral administration p histicola might delay development t1d nonobese diabetic nod mice assess used following materials methods female nod mice ages 58 weeks administered every day p histicola cultured inhouse blood glucose levels measured every week mice sacrificed various time points histopathological analysis pancreas modulation immune response commensal tested analyzing regulatory tcells nkp46+ cells using flow cytometry intestinal cytokine mrna transcript levels using quantitative rtpcr microbial composition 16 s rrna gene analysis conducted stool samples collected various time pointsresultsadministration p histicola nod mice delayed onset t1d beta diversity fecal microbiomes demonstrated microbial composition mice administered p histicola different treated treatment p histicola led significant increase regulatory t cells concomitant decrease nkp46+ cells pancreatic lymph nodes compared untreated group 5 weeks treatmentconclusionsthese observations suggest p histicola treatment delayed onset diabetes increasing levels regulatory t cells pancreatic lymph nodes preliminary work supports rationale enteral exposure non pathogenic commensal p histicola tested future therapy t1d,0.0
developmental deficits staging dynamics age associated alzheimers disease neurodegeneration neuronal loss subjects syndrome abstractthe increased life expectancy individuals syndrome ds associated increased prevalence trisomy 21linked earlyonset alzheimers disease eoad dementia aims study 14 brain regions including entorhinal cortex hippocampus basal ganglia cerebellum 33 adults ds 2672 years age identify magnitude brain regionspecific developmental neuronal deficits contributing intellectual deficits apply baseline identification topography magnitude neurodegeneration neuronal volume losses caused eoad establish agebased staging pattern genetically driven neuropathology ds ds subject age stage dementia strongly correlated strong predictors adassociated decrease number neurons considered major contributor dementia ds cohort subclassified age pread stage 2641yearold subjects full spectrum developmental deficit limited incipient ad pathology 4349 5159 6172yearold groups predominant prevalence mild moderately severe severe dementia respectively multiregional study revealed 281 developmental neuronal deficit ds subjects 2641 years age 119 adassociated neuronal loss ds subjects 4349 years age 280 maximum neuronal loss 5159 years age 110 minimum neuronal loss 6172 years age total developmental neuronal deficit 408 million neurons adassociated neuronal loss 416 million neurons reflect comparable magnitude developmental neuronal deficit contributing intellectual deficits adassociated neuronal loss contributing dementia highly predictable pattern pathology indicates successful treatment ds subjects fourth decade life may prevent ad pathology functional decline,0.0
mitochondrial dysfunctions neurodegenerative diseases role disease pathogenesis strategies analysis therapeutic prospects neural regen res 2022 apr 17 4 754758 doi 104103 16735374322430abstractfundamental organelles occur every cell type exception mammal erythrocytes mitochondria required multiple pivotal processes include production biological energy biosynthesis reactive oxygen species control calcium homeostasis triggering cell death disruption anyone processes shown impact strongly function cells especially neurons review discuss role mitochondria impairment development neurodegenerative diseases amyotrophic lateral sclerosis parkinsons disease alzheimers disease highlight mitochondria disruption revolves around processes underlie mitochondrias life cycle fusion fission production reactive oxygen species energy failure genetic sporadic forms neurodegenerative diseases unavoidably accompanied often caused dysfunction one key mitochondrial processes therefore order get depth insights health status neurodegenerative diseases need focus innovative strategies aimed characterizing various mitochondrial processes current techniques include mitostress mitotracker transmission electron microscopy oxidative stress assays along expression measurement proteins maintain mitochondrial health will also discuss panel approaches aimed mitigating mitochondrial dysfunction include canonical drugs natural compounds supplements lifestyle interventions innovative approaches mitochondria transplantation gene therapy conclusion mitochondria fundamental organelles necessary virtually cell functions severely impaired neurodegenerative diseases critical develop novel methods measure mitochondrial state novel therapeutic strategies aimed improving healthpmid34472461 doi104103 16735374322430,0.0
y chromosome moving sex determination shadow abstractalthough sex hormones play key role sex differences susceptibility severity outcomes response therapy different diseases sex chromosomes also increasingly recognized important factor studies demonstrated y chromosome genetic wasteland can useful genetic marker interpreting various malespecific physiological pathophysiological characteristics y chromosome harbors malespecific genes either solely cooperation xcounterpart independent conjunction sex hormones considerable impact basic physiology disease mechanisms tissues development furthermore loss y chromosome aberrant expression y chromosome genes cause sex differences disease mechanisms launch human proteome project hpp association y chromosome proteins pathological conditions increasingly explored review involvement y chromosome genes malespecific diseases prostate cancer cases prevalent men cardiovascular disease neurological disease cancers highlighted understanding molecular mechanisms underlying y chromosomerelated diseases can significant impact prevention diagnosis treatment diseases,0.0
palliative care prehospital service brazil experiences health professionals background integrated care network emergency specialized primary care services can prevent repeated hospitalizations institutionalized death terminally ill patients palliative care pc identify perception health professionals regarding concept pc care experiences type patient prehospital care phc service brazilmethodsstudy qualitative approach interpretative nature based perspective ricoeurs dialectical hermeneuticsresultsthree central themes emerged professionals speeches 1 unpreparedness team 2 decision making 3 dysthanasiaconclusionsit necessary invest professional training associated pc home context principles affirming life considering death normal process rushing postponing death integrating psychological spiritual aspects patient family care including grief counseling improved quality life adopting specific policy pc involves levels care including phc adopt unified information system well effective procedures favor respect patients will without generating dissatisfaction team family,0.0
clinical outcomes dengue virus infection pregnant nonpregnant women reproductive age retrospective cohort study 2016 2019 paran brazil background increasing number dengue cases worldwide implies greater exposure atrisk groups pregnant women denv infection pregnancy increasingly associated unfavorable outcomes evolution disease clinical outcomes remain unclear objective study characterize dengue cases reproductive aged women comparing development disease pregnant nonpregnant womenmethodsa population based retrospective cohort study used data reported brazilian mandatory notifiable diseases information system 2016 2019 paran brazil compared sociodemographic clinical laboratory variables pregnant nonpregnant women hospitalization disease severity classification dengue dengue warning signs severe dengue considered outcome variablesresultsthe two groups differences year notification age distribution region residence laboratory investigation frequent among pregnant women denv2 prevailed groups risks hospitalization development severe dengue higher pregnant women deaths observed among pregnant womenconclusionthis study identified pregnancy risk factor increase severity denv infection reinforces importance identifying early signs complication close monitoring adequate treatment pregnant women,0.0
perceived burden family functioning among informal caregivers individuals living schizophrenia tanzania crosssectional study background globally families play critical role providing care support persons living schizophrenia important identify potentially modifiable factors influence perceived caregiver burden order properly address needs caregivers especially relevant lowresource settings psychiatric services scarce interventions effective targeted individual living schizophrenia caregiver study examines correlates perceived burden among informal caregivers individuals schizophrenia tanzania particular association burden caregiverreported family functioningmethodsthis study used baseline data individually randomized controlled trial 65 pairs individuals schizophrenia informal caregivers dar es salaam mbeya tanzania caregiver burden measured using burden assessment scale univariable multivariable regression analyses performed determine relationship caregiver burden family functioning explore correlates burdenresultssixtythree percent caregivers reported experiencing high burden result caring relative schizophrenia multivariable regression analyses revealed poor family functioning caregiver employed associated high caregiver burden higher levels hopefulness caregiver associated low caregiver burdenconclusioncaregivers employed reported poor family functioning low levels hopefulness likely perceive high caregiver burden future interventions aiming reduce caregiver burden may benefit improving family functioning nurturing hope among caregivers individuals living schizophrenia policies programs cognizant needs caregivers work addition providing care relative schizophrenia order better support,0.0
diphtheria toxin induced csf1r inhibitor mediated microglia ablation model leads loss csf#x2f ventricular spaces vivo independent cytokine upregulation background two recently developed novel rodent models reported ablate microglia either genetically targeting microglia via cx3cr1creer idtr + dtx pharmacologically targeting csf1r receptor inhibitor plx5622 models widely used recent years define essential functions microglia led high impact studies moved field forwardmethodsusing either cx3cr1idtr mice combination dtx via plx5622 diet pharmacologically ablate microglia compared two models via mri histology study general anatomy brain csf ventricular systems additionally analyzed cytokine profile microglia ablation modelsresultswe discovered genetic ablation cx3cr1idtr + dtx pharmacological microglia ablation plx5622 displays surprisingly rapid pathological condition brain represented loss csf ventricles without brain parenchymal swelling phenotype observed mri histological analysis surprise discovered idtr allele alone leads loss csf ventricles phenotype following diphtheria toxin dtx treatment independent cre expression examine underlying mechanism loss csf cx3cr1idtr ablation idtr models additionally investigated cytokine profile cx3cr1idtr + dtx idtr + dtx plx models found increases multiple cytokines cx3cr1idtr + dtx pharmacological ablation model idtr + dtx mouse brains time csf loss 3 days first dtx injection result suggests upregulation cytokines cause loss csf supported data indicating brain parenchyma swelling edema observed cx3cr1idtr + dtx microglia ablation model additionally pharmacological inhibition kc cxcr2 pathway upregulated cytokine cx3cr1idtr + dtx model resolve csf ventricular loss phenotype genetic microglia ablation model instead cx3cr1idtr + dtx ablation idtr + dtx models showed increased activated iba1 + cells choroid plexus cp suggesting cprelated pathology might contributing factor observed csf ventricular shrinkage phenotypeconclusionsour data first time reveal robust global csf ventricular space shrinkage pathology cx3cr1idtr genetic ablation model caused idtr allele plx5622 ablation model suggest pathology due brain edema formation cp related pathology given wide utilization idtr allele cx3cr1idtr model crucial fully characterize pathology understand underlying causal mechanisms specifically caution needed utilizing model interpret subtle neurologic functional changes thought mediated microglia instead due csf ventricular loss genetic ablation model,0.0
therapy development spinal muscular atrophy perspectives muscular dystrophies neurodegenerative disorders background major efforts made last decade develop improve therapies proximal spinal muscular atrophy sma introduction nusinersen spinraza antisense oligonucleotide therapy onasemnogene abeparvovec zolgensma aav9based gene therapy risdiplam evrysdi small molecule modifier premrna splicing set new standards interference neurodegenerationmain bodytherapies sma designed interfere cellular basis disease modifying premrna splicing enhancing expression survival motor neuron smn protein expressed low levels disorder corresponding strategies also can applied disease mechanisms caused loss function toxic gain function mutations development therapies sma based use cell culture systems mouse models well innovative clinical trials included readouts originally introduced optimized preclinical studies summarized first part review second part discusses current developments perspectives amyotrophic lateral sclerosis muscular dystrophies parkinsons alzheimers disease well obstacles need overcome introduce rnabased therapies gene therapies disordersconclusionrnabased therapies offer chances therapy development complex neurodegenerative disorders amyotrophic lateral sclerosis muscular dystrophies parkinsons alzheimers disease experiences made new drugs sma also experiences aav gene therapies help broaden spectrum current approaches interfere pathophysiological mechanisms neurodegeneration,0.0
decreased mitochondrial dloop region methylation mediates increase mitochondrial dna copy number cadasil background cerebral autosomal dominant arteriopathy subcortical infarcts leukoencephalopathy cadasil typical neurodegenerative disease associated mitochondrial dysfunction methylation dloop region mitochondrial dna copy number mtdnacn play critical role maintenance mitochondrial function however association dloop region methylation mtdnacn cadasil remains unclearmethodsoverall 162 individuals recruited including 66 cadasil patients 96 age sexmatched controls extracting genomic dna peripheral white blood cells levels dloop methylation mtdnacn assessed using methyltarget sequencing realtime pcr respectivelyresultswe observed increased mtdnacn decreased dloop methylation levels cadasil patients compared control group regardless gender stratification besides found negative correlation dloop methylation levels mtdnacn mediation effect analysis shows proportion association mtdnacn cadasil mediated dloop methylation 116 95 ci 56 226 gender stratification proportions associations mediated dloop methylation males females 72 95 ci 24 198 220 95 ci 74 501 respectivelyconclusiondecreased methylation dloop region mediates increased mtdnacn cadasil may caused compensatory mechanism mitochondrial dysfunction patients cadasil,0.0
ontogeny rort+ cells intestine newborns role development experimental necrotizing enterocolitis background neonates possess immature plastic immune system major cause diseases newborns necrotizing enterocolitis nec severe devastating intestinal disease typically affects premature infants however development intestinal immune cells neonates roles pathological process nec elucidatedresultswe examined ontogeny intestinal lamina propria lymphocytes early life mice found high percentage rort+ cells containing inflammatory th17 ilc3 populations first week life importantly proportion rort+ cells intestinal lamina propria increased nec mice patients tissue control furthermore application gsk805 specific antagonist rort inhibited il17a release ameliorated nec severityconclusionsour data reveal high proportion rort+ cells newborn mice may directly contribute development nec,0.0
neuroprotective effects lippia javanica burmf spreng herbal tea infusion leadinduced oxidative brain damage wistar rats background though lippia javanica burmf spreng antioxidant activity demonstrated effect protecting brain lead pb induced oxidative damage unknown study investigated effect l javanica pbinduced oxidative stress inflammation apoptosis acetylcholinesterase activity rats brainmethodsl javanica herbal tea infusion prepared phytochemical constituent revealed liquid chromatographymass spectrometer lcms administered simultaneously pb four groups male wistar rats n 5 group used control received distilled water pbacetate group received 50 mg pb kg bodyweight bw treatment group received 50 mg pb kg pbacetate + 5 ml kg bw l javanica l javanica group received 5 ml kg bw l javanica tea infusion 6 weeks treatment oxidative status acetylcholinesterase activity inflammation apoptosis assessed brain tissue also histologically examinedresultsmean brain heart weight reduced p 005 liver spleen weights increased p 005 pb exposed animals prevented l juvanica treatment treatment l javanica increased p 005 overall brain antioxidant status glutathione superoxide dismutase activities reduced lipid peroxidation p 005 compared pb exposed animals proinflammatory cytokine tumour necrotic factoralpha proapoptosis bax protein anticholinesterase activity reduced p 005 pbl javanica treated animals compared pb exposed group histological examination confirmed neuroprotective effects l javanica evidenced reduced apoptosis necrosis inflammationinduced vacuolization oedema hippocampus l javanica treatment alone detrimental effects rats lcms analysis revealed l javanica rich phenolicsconclusionsthis study demonstrated l javanica rich phenolics effective reducing pbinduced brain oxidative stress inflammation apoptosis acetylcholinesterase activity neuronal damage,1.0
intramedullary parasite eggs latent three decades mimicking acute transverse myelitis background intramedullary parasitic infection extremely uncommon clinical presentation brownsequard syndrome even rarercase presentationthe authors report case involving 57yearold woman brownsequard syndrome magnetic resonance imaging clinical epidemiological features similar acute transverse myelitis myelotomy suggested inflammation caused latent parasite eggs spinal cord antiparasitic steroid therapies administered postoperatively authors knowledge first report describe surgical experience taenia solium eggs spinal cordconclusionintramedullary parasitic infection diagnostic challenge requires careful discrimination diseases parasite infection suspected progressively deteriorating patient myelotomy considered rapid accurate treatment,0.0
osmotic pumpbased drugdelivery vivo remyelination research central nervous system j vis exp 2021 dec 17 178 doi 103791 63343abstractdemyelination identified multiple sclerosis ms also central nervous system diseases alzheimers disease autism evidence suggests remyelination can effectively ameliorate disease symptoms increasing focus drug development promote myelin regeneration process thus regionselectable resultreliable drug delivery technique required test efficiency specificity drugs vivo protocol introduces osmotic pump implant new drug delivery approach lysolecithininduced demyelination mouse model osmotic pump small implantable device can bypass bloodbrain barrier bbb deliver drugs steadily directly specific areas mouse brain can also effectively improve bioavailability drugs peptides proteins short halflife therefore method great value field central nervous system myelin regeneration researchpmid34978294 doi103791 63343,1.0
possible association pm25 neurodegenerative diseases systematic review environ res 2021 dec 31112581 doi 101016 jenvres2021112581 online ahead printabstractair pollution one serious environmental problems afflict planet one greatest risk factors human health particular pm25 able cross bloodalveolar bloodbrain barriers thus increasing onset respiratory cardiovascular neurodegenerative diseases neurodegenerative disease progressive neuronal dysfunction leads neuronal lesions structure function includes several diseases alzheimers disease ad parkinsons disease pd vascular dementia vad multiple sclerosis ms others carried systematic review using prisma approach investigate possible association exposure pm25 neurodegenerative diseases international databases pubmed science direct web sciences used find published studies topic search period january 2011 june 2021 2000 full research articles selected finally included 20 fullresearch articles selected studies highlighted pm25 exposure can associated onset neurodegenerative diseases ad pd ms vad association depends age pm25 levels exposure time also exposure air pollutants proximity areas high vehicular traffic presence comorbidities exposure pm25 promotes neuroinflammation processes breathing particles can reach nasal epithelial mucosa transferred brain olfactory bulb furthermore exposure pm25 associated increased expression markers neurodegenerative diseases eg alphasynuclein betaamyloid can contribute etiopathogenesis neurodegenerative diseases although many studies revealed pathological relationship pm25 exposure cognitive impairment potential cellular molecular mechanisms pm25 leading neurodegenerative disease remain entirely clear studies need carried topicpmid34979121 doi101016 jenvres2021112581,0.0
schizoaffective disorder concurrent rhabdomyolysis cureus 2021 nov 25 13 11 e19896 doi 107759 cureus19896 ecollection 2021 novabstractthe authors present unique case schizoaffective disorder exacerbation complicated substance misuse rhabdomyolysis acute renal injury patient recently released jail psychiatric medications aside family reported bizarre behavior involving patient spending significant amount time outdoor hot tub exposed extreme heat patient justified necessary protect snakes patient diagnosed severe dehydration rhabdomyolysis managed primary care team hospital setting specialist input psychiatry renal departments patient exhibited paranoid ideations toward medical team times agitated combative resolution distrust pivotal successful treatment made possible trilateral communication patient police officers medical staffpmid34976507 pmcpmc8712212 doi107759 cureus19896,0.0
ataxin2 essential cytoskeletal dynamics neurodevelopment drosophila iscience 2021 dec 3 25 1 103536 doi 101016 jisci2021103536 ecollection 2022 jan 21abstractataxin2 atx2 highly conserved rna binding protein atx2 undergoes polyglutamine expansion leading amyotrophic lateral sclerosis als spinocerebellar ataxia type 2 sca2 however physiological functions atx2 neurons remain unknown using powerful genetics drosophila show atx2 essential normal neuronal cytoskeletal dynamics organelle trafficking upon neuronspecific atx2 loss microtubule actin networks abnormally stabilized cargo transport drastically inhibited depletion atx2 caused multiple morphological defects nervous system third instar larvae include reduced brain size impaired axon development decreased dendrite outgrowth defects nervous system caused loss ability crawl lethality pupal stage taken together data mark atx2 major regulator cytoskeletal dynamics denote atx2 essential gene neurodevelopment well neurodegenerative factorpmid34977501 pmcpmc8689088 doi101016 jisci2021103536,0.0
rhabdomyoma hypoplastic left heart syndrome case report rare combination cureus 2021 nov 25 13 11 e19900 doi 107759 cureus19900 ecollection 2021 novabstractthe benign cardiac tumor pediatric population cardiac rhabdomyoma known associated tuberous sclerosis complex report case multiple cardiac rhabdomyomas another rare anomaly heart known hypoplastic left heart syndrome fetus antenatally diagnosed echocardiography showed rhabdomyoma hypoplastic left heart patient started prostaglandin immediately birth confirmed postnatally inoperable congenital hypoplastic left heart syndrome third day baby started progressive bradycardia diedpmid34976510 pmcpmc8712222 doi107759 cureus19900,0.0
effect gadoliniumbased contrastagents automated brain atrophy measurements freesurfer patients multiple sclerosis eur radiol 2022 jan 3 doi 101007 s00330021084058 online ahead printabstractobjective determine whether reliable brain atrophy measures can obtained postcontrast 3d t1weighted images patients multiple sclerosis ms using freesurfermethods twentytwo patients ms included 3d t1weighted mr images obtained scanner visit acquisition protocol administration gadoliniumbased contrast agents gbcas two freesurfer versions v601 v711 applied calculate grey matter gm white matter wm volumes global regional cortical thickness consistency measures obtained pre postcontrast images assessed intraclass correlation coefficient icc difference investigated paired ttests mean percentage increase decrease calculated total wm gm matter volume total deep gm thalamus volume mean cortical thicknessresults good excellent reliability found investigated measures icc ranging 0926 0996 p values 0001 gm volumes cortical thickness measurements significantly higher postcontrast images 31 174 total wm volume decreased significantly 17 p values 0001 conclusion consistency values obtained pre postcontrast images excellent suggesting may possible extract reliable brain atrophy measurements t1weighted images acquired administration gbcas using freesurfer however absolute values systematically different pre postcontrast images meaning images compared directly potential systematic effects possibly dependent gbca dose delay time contrast injection investigatedtrial registration clinical trialsgov identifier nct00360906key points influence gadoliniumbased contrast agents gbcas atrophy measurements still largely unknown challenges use considerable source historical prospective realworld data 22 patients multiple sclerosis consistency brain atrophy measurements obtained pre postcontrast images excellent suggesting may possible extract reliable atrophy measurements t1weighted images acquired administration gbcas using freesurfer absolute values systematically different pre postcontrast images meaning images compared directly measurements extracted certain regions eg temporal pole interpreted cautionpmid34978580 doi101007 s00330021084058,0.0
evaluation ureabased inhibitors dopamine transporter using experimental autoimmune encephalomyelitis model multiple sclerosis acs chem neurosci 2022 jan 3 doi 101021 acschemneuro1c00647 online ahead printabstractthe dopaminergic system involved regulation immune responses various homeostatic disease conditions conditions parkinsons disease multiple sclerosis ms pharmacological modulation dopamine da system activity thought therapeutic relevance providing basis using dopaminergic agents treatment relevant states particular proposed restoration da levels may inhibit neuroinflammation recently reported new class dopamine transporter dat inhibitors high selectivity dat gprotein coupled receptors tested continue evaluation monoamine transporter inhibitors furthermore show urealike dat inhibitor compound 5 statistically significant antiinflammatory effects attenuates motor deficits pain behaviors experimental autoimmune encephalomyelitis model mimicking clinical signs ms best knowledge first study reporting beneficial effects dat inhibitorbased treatment animals induced autoimmune encephalomyelitis observed results provide additional support model darelated neuroinflammationpmid34978174 doi101021 acschemneuro1c00647,0.0
treatment cd52 antibody protects neurons experimental autoimmune encephalomyelitis mice recovering phase front immunol 2021 dec 16 12792465 doi 103389 fimmu2021792465 ecollection 2021abstractmultiple sclerosis ms chronic autoimmune disease driven t b lymphocytes remyelination failure neurodegeneration results permanent clinical disability ms patients desirable therapy modulate immune system also promote neuroprotection remyelination investigate neuroprotective effect cd52 antibody ms c57bl 6j sjl mice experimental autoimmune encephalomyelitis eae treated cd52 antibody peak disease treatment cd52 antibody depleted t b lymphocytes blood reduced infiltration t lymphocytes microglia macrophages spinal cord anticd52 therapy attenuated eae scores recovery phase protected neurons immediately treatment within 4 days shown reducing accumulation amyloid precursor proteins potentially promoted remyelination increased number olig2 cc1positive mature oligodendrocytes prevented myelin loss following days eg 14 days post treatment experiments eae mice conditional knockout bdnf neurons administered cd52 antibodies neuronal deficiency bdnf attenuated effect anticd52 treatment reducing eae scores inflammatory infiltration affect anticd52 treatmentinduced improvement myelin coverage spinal cord summary anticd52 therapy depletes cd4positive t lymphocytes prevents myelin loss protects neurons eae mice neuronal bdnf regulates neuroprotective antiinflammatory effect cd52 antibody eae micepmid34975892 pmcpmc8716455 doi103389 fimmu2021792465,1.0
altered plasma metabolic profiles chinese patients multiple sclerosis front immunol 2021 dec 15 12792711 doi 103389 fimmu2021792711 ecollection 2021abstractmultiple sclerosis ms autoimmune disease leads demyelination nerve axons increasing number studies suggest patients ms exhibit altered metabolic profiles might contribute course ms however alteration metabolic profiles chinese patients ms potential roles regulating immune system remain elusive study performed global untargeted metabolomics approach plasma samples 22 msaffected chinese patients 21 healthy subjects total 42 differentially abundant metabolites dams belonging amino acids lipids carbohydrates identified plasma ms patients compared healthy controls observed evident reduction levels amino acids ltyrosine lisoleucine ltryptophan whereas great increase levels lglutamic acid lvaline msaffected patients levels lipid carbohydrate metabolites sphingosine 1phosphate myoinositol also reduced patients ms addition concentrations proinflammatory cytokines il17 tnf significantly increased whereas several antiinflammatory cytokines chemokines il1ra il7 mip1 distinctly reduced plasma ms patients compared healthy subjects interestingly dams ltryptophan sphingosine 1phosphate showed evident negative correlation changes level tnf il17 tightly positively correlating altered concentrations antiinflammatory cytokines chemokines mip1 rantes results revealed altered metabolomic profiles might contribute pathogenesis course ms disease modulating immunoinflammatory responses peripheral system essential eliciting autoimmune responses central nervous system thus resulting progression ms study provides potential clues developing therapeutic strategies ms near futurepmid34975894 pmcpmc8715987 doi103389 fimmu2021792711,1.0
polymorphisms cyp2r1 rs10766197 cyp27b1 rs10877012 multiple sclerosis casecontrol study j immunol res 2021 dec 23 20217523997 doi 101155 2021 7523997 ecollection 2021abstractbackground multiple sclerosis ms chronic autoimmune inflammatory disease low vitamin d levels reported risk factor ms genetic variances implicated aim study evaluate association ms rs10766197 polymorphism cyp2r1 gene rs10877012 polymorphism cyp27b1 gene second aim analyse whether polymorphisms associated severity progression ms material methods casecontrol study included 116 ms patients 226 controls mexican mestizo ms diagnosed mcdonald criteria 2017 complete neurological evaluation performed evaluate severity disease progression serum 25hydroxyvitamin d 25 oh vitamin d levels measured elisa single nucleotide polymorphisms rs10766197 cyp2r1 gene rs10877012 snp cyp27b1 gene genotyped realtime pcrresults serum 25 oh vitamin d levels lower ms patients controls p 0009 differences observed serum 25 oh vitamin d levels ms patients severe progression compared low progression p 088 higher frequency allele cyp2r1 rs10766197 observed ms patients controls p 005 differences observed frequency t allele cyp27b1 rs10877012 p 065 subanalysis patients ga + aa genotypes cyp2r1 rs10766197 increased risk ms compared controls p 003 increased risk observed gt + tt genotypes cyp27b1 rs10877012 p 063 differences observed allele frequencies either polymorphism patients severe vs low disease progressionconclusion lower serum 25 oh vitamin d levels observed ms patients controls although levels associated disease progression carriers ga + aa genotypes cyp2r1 rs10766197 increased risk ms none polymorphisms associated severe progression mspmid34977256 pmcpmc8718303 doi101155 2021 7523997,0.0
canadian physicians#39 use perioperative botulinum toxin injections spastic limbs crosssectional national survey arch rehabil res clin transl 2021 oct 8 3 4 100158 doi 101016 jarrct2021100158 ecollection 2021 decabstractobjective investigate practice patterns canadian physicians use perioperative botulinum toxin bont injections improve surgical outcomes spastic limbsdesign crosssectional national survey composed invitation email 18item questionnaire disseminated national physical medicine rehabilitation pmr society 138 physician members involved spasticity managementsetting applicableparticipants twentyfive percent participants n34 fully completed surveyinterventions applicablemain outcome measures participants completed online questionnaire examined practice patterns surgical outcomes associated perioperative bont injectionsresults majority n21 84 canadian physicians inject bont perioperatively improve outcomes surgeries performed spastic limbs specialists pmr practicing academic settings respondents 74 used bont injections perioperative treatment patients limb spasticity undergoing surgery surveyed 65 physicians used bont preoperatively 21 used bont intraoperatively 24 used bont postoperativelyof physicians performed bont injections preoperatively 6 performed bont injections 7 12 weeks preoperatively 32 performed bont injections 4 6 weeks preoperatively 47 performed bont injections 2 3 weeks preoperatively 15 performed bont injections 0 1 week preoperatively majority physicians 85 responded injecting bont perioperatively may improve patients surgical outcome participants 100 stated bont contribute perioperative complications adverse effects qualitative responses emphasized successful outcomes perioperative bont linked enhanced collaboration surgeons research needed determine optimal timing perioperative bontconclusion canadian physicians mostly pmr specialists administer perioperative bont improve outcomes surgeries performed spastic limbs optimal timing perioperative bont suggested 2 3 weeks surgery 47 survey respondents participating physicians responded perioperative bont contribute known perioperative complications adverse events study highlights importance conducting robust research better understand optimal timing perioperative bont injection enhancing collaboration physicians surgeons increasing awareness perioperative bont planning surgeries spastic limbspmid34977540 pmcpmc8683856 doi101016 jarrct2021100158,0.0
editorial microbial view central nervous system disorders interplay microorganisms neuroinflammation behaviour front immunol 2021 dec 16 12816227 doi 103389 fimmu2021816227 ecollection 2021no abstractpmid34975927 pmcpmc8716445 doi103389 fimmu2021816227,0.0
potential drug interactions multiple sclerosis covid19 therapies turk j pharm sci 2021 dec 31 18 6 665666 doi 104274 tjpsgalenos202192892no abstractpmid34978395 doi104274 tjpsgalenos202192892,0.0
therapeutic application rtms atypical parkinsonian disorders behav neurol 2021 dec 23 20213419907 doi 101155 2021 3419907 ecollection 2021abstractthe terms atypical parkinsonian disorders apds parkinson plus syndromes mainly used describe four major entities sporadic neuronal multisystem degeneration progressive supranuclear palsy psp corticobasal degeneration cbd multiple system atrophy msa dementia lewy bodies lbd apds characterized variety symptoms lack disease modifying therapies treatment thus remains mainly symptomatic brain stimulation via repetitive transcranial magnetic stimulation rtms safe noninvasive intervention using magnetic coil considered alternative therapy various neuropsychiatric pathologies paper review available studies investigate efficacy rtms treatment apds parkinson plus syndromes majority studies shown beneficial effects motor nonmotor symptoms research still preliminary phase large doubleblind studies lacking literaturepmid34976231 pmcpmc8718319 doi101155 2021 3419907,0.0
soluble receptor isoform ifnbeta sifnar2 multiple sclerosis patients association clinical response ifnbeta treatment front immunol 2021 dec 16 12778204 doi 103389 fimmu2021778204 ecollection 2021abstractpurpose interferon beta receptor 2 subunit ifnar2 can produced transmembrane protein also soluble form sifnar2 generated alternative splicing proteolytic cleavage agonist antagonist activities ifn however role regarding clinical response ifn relapsingremitting multiple sclerosis rrms unknown aim evaluate vitro shortterm effects 6 12 months ifn therapy sifnar2 production association clinical response ms patientsmethods ninetyfour rrms patients included evaluated baseline 6 12 months treatment onset subset 41 patients classified responders nonresponders ifn therapy sifnar2 serum levels measured elisa mrna expression ifnar1 ifnar2 splice variants mxa proteases assessed rtpcr shortterm effect evaluated pbmc rrms patients ifn stimulation vitroresults protein mrna levels sifnar2 increased ifn treatment according clinical response nonresponders increased sifnar2 significantly protein mrna levels sifnar2 gene expression correlated transmembrane isoform expression 23fold higher mxa gene expression increased significantly treatment ifnar1 ifnar2 slightly increased shortterm ifn vitro induction pbmc 6 7 patients increased sifnar2 expressionconclusions ifn administration induces production sifnar2 rrms higher levels might associated reduction therapeutic response thus levels sifnar2 monitored optimize effective response ifn therapypmid34975865 pmcpmc8716373 doi103389 fimmu2021778204,0.0
t cellmediated autoimmunity glaucoma neurodegeneration front immunol 2021 dec 16 12803485 doi 103389 fimmu2021803485 ecollection 2021abstractglaucoma leading neurodegenerative disease leads blindness 36 million people aged 50 years older worldwide many decades glaucoma therapy primarily focused controlling intraocular pressure iop sound evidence supports role delaying progress retinal ganglial cell rgc damage protecting patients vision loss meanwhile accumulating data point immunemediated attack neural retina underlying pathological process behind glaucoma may come independent raised iop recently scholars suggested autoimmune aspects glaucoma autoreactive t cells mediating chief pathogenic process autoimmune process well pathological features glaucoma largely overlaps neurodegenerative diseases central nervous system cns including alzheimers disease parkinsons disease multiple sclerosis addition immune modulation therapy regarded potential solution glaucoma boosted trials cns neurodegenerative diseases thus novel insights t cellmediated immunity treatment cns neurodegenerative diseases may serve valuable inspirations ophthalmologists review focuses role t cellmediated immunity pathogenesis glaucoma discusses potential applications relevant findings cns neurodegenerative diseases future glaucoma researchpmid34975917 pmcpmc8716691 doi103389 fimmu2021803485,0.0
synthesis pharmacological characterization visabron backbone cyclic peptide dual antagonist alpha4beta1 vla4 #x2f alpha9beta1 integrin therapy multiple sclerosis jacs au 2021 nov 24 1 12 23612376 doi 101021 jacsau1c00496 ecollection 2021 dec 27abstractintegrins 41 91 important pathogenesis progression inflammatory autoimmune diseases roles leukocyte activation trafficking natalizumab monoclonal antibody selectively targeting 41 integrin blocking leukocyte trafficking central nervous system immunotherapy multiple sclerosis ms however due adverse effects associated chronic treatment alternative strategies using small peptide mimetic inhibitors sought present study synthesized characterized visabron c 44 backbone cyclic octapeptide based sequence tmld nonrgd unique 41 integrin recognition sequence motif derived visabres proteinous disintegrin viper venom visabron c 44 selected minilibrary conformational diversity based potency selectivity functional adhesion cellular assays visabron c 44 s serum stability pharmacokinetics therapeutic effects following ip injection assessed experimental autoimmune encephalomyelitis eae animal model furthermore visabron c 44 s lack toxic effects mice verified blood analysis tissue pathology immunogenicity offtarget effects indicating significant tolerability lack immunogenicity visabron c 44 can delivered systemically vitro vivo data justify visabron c 44 safe alternative peptidomimetic lead compound drug monoclonal anti4 integrin antibodies steroids immunosuppressant drugs moreover visabron c 44 design may pave way developing new therapies variety inflammatory autoimmune diseasespmid34977904 pmcpmc8717366 doi101021 jacsau1c00496,0.0
dendrimer2pmpa selectively blocks upregulated microglial gcpii activity improves cognition mouse model multiple sclerosis nanotheranostics 2022 jan 1 6 2 126142 doi 107150 ntno63158 ecollection 2022abstractcognitive impairment common aspect multiple sclerosis ms treatments reduced brain nacetylaspartylglutamate naag levels linked impaired cognition various neurological diseases including ms naag levels regulated glutamate carboxypeptidase ii gcpii hydrolyzes neuropeptide nacetylaspartate glutamate gcpii activity upregulated multifold microglia following neuroinflammation although several gcpii inhibitors 2pmpa elevate brain naag levels restore cognitive function preclinical studies given high systemic doses via direct brain injection none clinically available due poor bioavailability limited brain penetration hydroxyldendrimers successfully used selectively deliver drugs activated glia methods attached 2pmpa hydroxyl polyamidoamine pamam dendrimers d2pmpa using click chemistry approach cy5labelledd2pmpa used visualize selective glial uptake vitro vivo d2pmpa evaluated antiinflammatory effects lpstreated glial cultures experimental autoimmune encephalomyelitis eae immunized mice d2pmpa dosed biweekly starting disease onset cognition assessed using barnes maze gcpii activity measured cd11b+ hippocampal cells results d2pmpa showed preferential uptake microglia robust antiinflammatory activity including elevations naag tgf mglur3 glial cultures d2pmpa significantly improved cognition eae mice even though physical severity unaffected gcpii activity increased 20fold cd11b+ cells eae mice significantly mitigated d2pmpa treatment conclusions hydroxyl dendrimers facilitate targeted drug delivery activated microglia data support development d2pmpa attenuate elevated microglial gcpii activity treat cognitive impairment mspmid34976589 pmcpmc8671953 doi107150 ntno63158,1.0
nk cells innatelike t cells autologous hematopoietic stem cell transplantation multiple sclerosis front immunol 2021 dec 16 12794077 doi 103389 fimmu2021794077 ecollection 2021abstractmultiple sclerosis ms autoimmune disease central nervous system autoreactive t b cells play important roles lymphocytes nk cells innatelike t cells appear involved well name examples cd56bright nk cells described immunoregulatory nk cell subset ms innatelike t cells ms described brain lesions proinflammatory signatures autologous hematopoietic stem cell transplantation ahsct procedure used treat ms procedure includes hematopoietic stem progenitor cell hspc mobilization highdose chemotherapy combined antithymocyte globulin atg subsequent infusion patients hspcs reconstitute functional immune system ahsct inhibits ms disease activity effectively long time presumably due elimination autoreactive t cells performed multidimensional flow cytometry experiments peripheral blood lymphocytes 27 ms patients ahsct address potential influence nk innatelike t cells ahsct relative frequency absolute numbers cd56bright nk cells rise preahsct levels studied innatelike t cell populations decrease hence data support enhanced immune regulation cd56bright nk cells efficient reduction proinflammatory innatelike t cells ahsct ms observations contribute current understanding immunological effects ahsct mspmid34975899 pmcpmc8716406 doi103389 fimmu2021794077,0.0
national institutes health pathways prevention workshop physical activity health wheelchair users arch rehabil res clin transl 2021 oct 17 3 4 100163 doi 101016 jarrct2021100163 ecollection 2021 decabstracthealth benefits physical activity well recognized general population reducing risk chronic health conditions less known effects physical activity people currently using may use wheeled mobility devices future specifically individuals multiple sclerosis cerebral palsy spinal cord injury increased likelihood use wheeled mobility device december 13 2020 national institutes health convened pathways prevention workshop can physical activity improve health wheelchair users consider available scientific evidence clinical benefits harms physical activity people currently using may use wheeled mobility devices future aim developing recommendations fill gaps evidence base multidisciplinary team content area experts developed agenda evidencebased practice center prepared evidence report independent panel selected national institutes health attended workshop convened develop recommendations basis systematic review presentations public comments received workshop revised recommendations based public comments received final report summarizes panels findings identifies current gaps knowledge panel made recommendations new research efforts including novel methods new research infrastructure improve evidence base effects physical activity people currently using may use wheeled mobility devices futurepmid34977545 pmcpmc8683862 doi101016 jarrct2021100163,0.0
quantifying impact upper limb tremor quality life people multiple sclerosis comparison quest msis29 scales abstractbackgroundupper limb tremor common people multiple sclerosis pwms can affect day day function impacting tremor related quality life tremorqol quality life essential tremor questionnaire quest tremorqol scale however validated use pwms contrast multiple sclerosis impact scale msis29 ms health related qol msqol scale validated pwms aim study quantify tremorqol pwms using quest msis29 establish convergent validity quest scale msis29methodsdata derived existing registered clinical trial studying efficacy botox onabotulinumtoxina compared placebo pwmsrelated upper limb tremor actrn12617000379314 determined msrelated disability expanded disability status scale score edss tremor severity bain findley clinical tremor rating scale bain cerebellar function scale assessment rating ataxia sara upper limb manual dexterity 9 hole peg test 9hpt quest msis29 used quantify tremorqol msqol respectively convergent validity investigated examining correlation quest msis29 pattern correlation two scales compared edss sara bain 9hptresultsour cohort 57 patients 16 male 41 female mean age 476 moderate msrelated disability median edss score 5 iqr35 median bain score 8 indicating mild tremor severity corresponded mild moderately poor tremorqol given mean quest summary index qsi 457 qsi correlated tremor severity measured bain total score rs 55 0339 p 001 manual dexterity measured 9hpt rs 55 0304 p 005 ms disease activity measured edss rs 55 0347 p 001 msis29 also showed correlations edss 9hpt correlate bain total score strong relationship qsi msis29 pwms r 55 0709 p 001 conclusionin crosssectional study found msqol tremorqol pwms upper limb tremor reduced also first demonstrate tremorqol pwms upper limb tremor can measured using quest may better suited use pwms affected armtremor msis29 lack literature specifically address tremorqol pwms research warranted,0.0
hematological malignancies systemic lupus erythematosus clinical characteristics risk factors prognosisa casecontrol study background systemic lupus erythematosus sle chronic complex multisystem autoimmune disorder higher risks hematological malignancies hm observed sle patients associated higher mortality mechanism risk factors hm oncogenesis sle patients still investigation aim study explore clinical characteristics risk factors prognosis sle patients without hm chinese populationmethodsa retrospective casecontrolled study conducted 72 sle patients january 2013 december 2020 clinical laboratory data collected compared two groups patients hm without hm logistic regression analysis performed determine risk factors hm oncogenesis survival rate estimated kaplanmeier methods cox proportional hazards regression analysisresultsamong 72 sle patients study fifteen complicated hm 57 without hm identified incidence rate hm approximately 024 elevated standardized incidence ratios lymphoma leukemia 27559 12708 respectively patients hm older diagnosed sle higher frequency infection splenomegaly lower levels hemoglobin highdensity lipoprotein compared without hm fewer patients hm expressed positive antidsdna antibody 267 vs 667 p 0005 received hydroxychloroquine treatment 400 vs 860 p 0001 older age sle diagnosis or1122 95 ci 10371214 regarded independent risk factor hm oncogenesis female rr 0219 95 ci 00700681 hydroxychloroquine rr 0281 95 ci 00940845 protective factors mortality sle patientsconclusionssle patients older age increased risk hm carcinogenesis prognosis male patients sle tends poorer whether complicated hm association antinuclear antibody spectrum medication hm oncogenesis sle needs investigation,0.0
worsening physical functioning patients neuroinflammatory disease covid19 pandemic abstractobjectiveto quantify changes psychological wellbeing physical function reported people neurological inflammatory disease pwnid covid19 pandemicmethods1134 pwnid 868 control participants recruited five major academic medical centers northeast midatlantic us beginning april 2020 participants completed serial surveys throughout covid19 pandemic aimed quantify mood symptoms physical function analyzed crosssectionally smaller cohort analyzed longitudinallyresultsthroughout pandemic depression scores significantly different pwnid controls although higher proportion pwnid reported clinically significant depression study entry depression scores worsen time either group loneliness strongest predictor worse depression along older age male gender pwnid controls well lack disease modifying therapy use disease duration pwnid contrast physical disability worsened significantly time pwnid controls age dmt status comorbid health conditions emerged significant predictors physical functionconclusionsdepressive symptoms remained consistent pwnid controls throughout covid19 pandemic physical function worsened significantly time groups particularly impactful pwnid higher baseline levels physical disability underscores importance reinstituting services interventions facilitate exercise reconditioning population,0.0
multimodal emotion perception young elderly patients multiple sclerosis abstractbackgroundstudies suggest emotion recognition empathy impaired patients ms pwms nonetheless studies emotion recognition used facial stimuli restricted young samples rely selfreport assessments empathy aims study determine impact ms age multimodal emotion recognition facial emotions vocal emotional bursts socioemotional sensitivity reported participants informants also aim investigate associations emotion recognition socioemotional sensitivity cognitive measuresmethodswe recruited 13 young healthy controls hc 14 young pwms 14 elderly hc 15 elderly pwms underwent short neuropsychological battery experimental emotion recognition task including facial emotions vocal emotional bursts participants study informants completed revisedself monitoring scale rsms assess participantnulls socioemotional sensitivityresultsthere significant effect age group recognition facial emotions emotional vocal bursts hc performing significantly better pwms young participants performing better elderly participants interaction effect effects observed selfreported socioemotional sensitivity however lower socioemotional sensitivity pwms reported informants finally multimodal emotion recognition correlate socioemotional sensitivity correlated global cognitive severityconclusionpwms present multimodal emotion perception deficits results extend previous findings decreased emotion perception empathy group elderly pwms advancing age accentuate deficits however decreased socioemotional sensitivity reported pwms appear observed relatives correlate emotion perception impairments future studies investigate reallife impacts emotion perception deficits pwms,0.0
potential value home squarestepping exercises inactive older adults exploratory case study background older adults engage regular physical activity however research options partake regular exercise population reducing barriers enhancing enablers still reaching benefits neededmethodsusing embedded mixed methods 10 inactive older adults age 65 completed 3week squarestepping exercise intervention help overcome initial barriers activate initial enablers perform regular exercise physical activity level tracked home pedometer using median steps day seven days prepost measure aerobic intensity squarestepping exercises quantified via heart rate monitor supervised session participant interview asking barriers enablers regular exercise intervention modify based initial physical activity framework matrix used pull potential barriers compare contrast search patterns participants lower higher initial physical activity levelsresultsthe 3week squarestepping exercise intervention helped participants overcome barriers uncomfortable fitness facility body image activate enablers use home equipment convenience median total steps day increased 12 p 002 moderateintensity level reached 80 sample participants performing square stepping exercise supervised session common barriers suitable program hard keep intensity reported participants regardless initial physical activity levelconclusionregardless initial physical activity level inactive older adults can increase physical activity level recommended intensity overcome common barriers exercise performing squarestepping exercises especially intimidated fitness facility setting concerned body image longer intervention including participants using squarestepping exercises required understand squarestepping exercises can increase proportion older adults exercising regularly,0.0
neck pain global epidemiology trends risk factors background neck pain one common musculoskeletal disorders agestandardised prevalence rate 270 per 1000 population 2019 literature review describes global epidemiology trends associated neck pain exploring psychological biological risk factors associated initiation progression neck painmethodsthe pubmed database google scholar search engine searched may 21 2021 studies included used human subjects evaluated effects biological psychological factors occurrence progression neck pain reported epidemiologyresultspsychological risk factors longterm stress lack social support anxiety depression important risk factors neck pain terms biological risks neck pain might occur consequence certain diseases neuromusculoskeletal disorders autoimmune diseases also evidence demographic characteristics age sex can influence prevalence development neck pain although research neededconclusionsthe findings present study provide comprehensive informative overview useful prevention diagnosis management neck pain,0.0
central vein sign present infratentorial multiple sclerosis plaques abstractbackground purpose growing evidence supporting presence central vein sign cvs supratentorial brain imaging biomarker multiple sclerosis ms diagnosis recently using optimized susceptibilityweighted angiography swanvenule detected cvs 86 supratentorial white matter lesions wmls clinical setting images obtained 3t mri scanner despite relevance infratentorial compartment cvs prevalence infratentorial ms plaques investigated detail objective determine proportion ms infratentorial lesions showing cvs positivitymaterials methods included subjects ms brain diseases showing least one infratentorial lesion larger 3 mm 3dflair patients scanned 3t mri scanner ge medical systems discoverymr750 applying comprehensive protocol including postcontrast 3dflair swanvenule sequences cvs presence confirmed two trained ratersresults thirty mris subjects ms analyzed one hundred one infratentorial lesions detected flair 86 centered vein fifteen mris nonms group analyzed 19 lesions visible flair 16 positive cvsconclusions swanvenule detects infratentorial lesions highlights central vein ms plaques 3t mri occurs supratentorial brain infratentorial lesions perivenular,0.0
new spontaneous animal model ankylosing spondylitis found cynomolgus monkeys background ankylosing spondylitis progressive disabling joint disease affects millions worldwide given unclear etiology studies ankylosing spondylitis relied heavily druginduced transgenic rodent models retain partial clinical features obviously lack useful disease model conduct comprehensive mechanistic studiesmethodswe followed group cynomolgus monkeys joint lesions reported spinal stiffness 2 years conducting hematological testing radiographic examination family aggregation analysis pathological analysis genetic testingresultsthe results confirmed diseased animals suffered spontaneous ankylosing spondylitis clinical features recapitulating human ankylosing spondylitis disease progression manifested pathological changes biochemical indicators similar ankylosing spondylitis patientsconclusionthe study offers promising nonhuman primate model spontaneous ankylosing spondylitis may serve excellent substitute preclinical research,0.0
functions roles sestrins regulating human diseases abstractsestrins sesns highly conserved stressinducible metabolic proteins known protect organisms various noxious stimuli including dna damage oxidative stress starvation endoplasmic reticulum er stress hypoxia sesns regulate metabolism mainly activation key energy sensor ampdependent protein kinase ampk inhibition mammalian target rapamycin complex 1 mtorc1 sesns also play pivotal roles autophagy activation apoptosis inhibition normal cells conversely promoting apoptosis cancer cells functions sesns diseases metabolic disorders neurodegenerative diseases cardiovascular diseases cancer broadly investigated past decades however limited number reviews summarized functions sesns pathophysiological processes human diseases especially musculoskeletal system diseases one aim review discuss biological functions sesns pathophysiological process phenotype diseases significantly include new evidence musculoskeletal system another purpose explore whether sesns potential biomarkers targets future diagnostic therapeutic process,0.0
impact rituximab mexican patients multiple sclerosis singlecenter retrospective study abstractbackgroundmultiple sclerosis ms chronic autoimmune disease central nervous system cns b cells essential role disease pathogenesis therefore selective bcell depletion commonly used treat disease rituximab rtx chimeric anticd20 monoclonal antibody demonstrated reduced inflammatory activity radiological activity ms patients due economic constrains treatment access limitations rtx often used treatment alternative patients described center experience rtx treated ms patientsmethodsa singlecenter observational retrospective study conducted mexican cohort ms 2010 2020 patients confirmed ms diagnosisall patients received fixed scheme involving induction 1 g day one day 15 followed 500 mg1g every six months maintenance annual relapse rate arr progression index pi expanded disability status scale edss mri activity disease evaluated comparison nave nonnave patients also conductedresultsa total 85 patients included mean age diagnosis 3313 890 years 73 859 rrms 39 341 treatmentnave treated rtx 62 729 patients reached freeofrelapse status statistically significant decrease mean arr 082 036 014 95ci 009020 p00001 edss 025 ci 005 p0034 decrease t1 gdenhancing mri lesions 164 vs 012 ci 070230 p0004 29 294 patients achieved neda3 among patients 2 24 experienced infusionrelated mild adverse events serious adverse events reportedconclusionwe found significant clinical radiological improvement nave nonnave ms patients treated rtx,0.0
presence noncriteria manifestations negatively affects prognosis seronegative antiphospholipid syndrome patients multicenter study background seronegative antiphospholipid syndrome snaps often defined presence aps criteria manifestations negative antiphospholipid antibodies apl coexistence aps noncriteria manifestations nevertheless impact noncriteria features still unclear different note relevance one single apl positive determination patients aps manifestations another domain limited evidence aim compare course snaps singlepositive apl spapl patients individuals aps manifestations without noncriteria features apl positivity controls methodsretrospective analysis patients thrombosis obstetric morbidity assessed two european hospitals 2005 2020 patients divided snaps spapl control groups clinical characteristics comorbidities therapies comparedresultsa total 82 patients included snaps group 88 spapl group 185 control group cox regression model snaps displayed thrombosis recurrence controls hr 38 95 ci 2265 p 0001 even adjusting presence hereditary thrombophilia systemic lupus erythematosus contraceptive hormonal treatment spapl difference thrombosis recurrence reach statistical significance p 0078 indefinite anticoagulation p 0001 p 0008 respectively vitamin k antagonist vka use p 0001 cases common snaps spaplconclusionsnaps displayed thrombosis recurrence indefinite anticoagulation vka use controls without noncriteria manifestations presence features patients thrombosis negative apl may negatively impact clinical course,0.0
elsberg syndrome following acute immunosuppressive treatment multiple sclerosis relapse abstractfirst described 80 years ago elsberg syndrome es continues underrecognized cause cauda equina syndrome ces es infectious disorder presents lower thoracic lumbosacral myelitis conjunction ces often occurs setting herpes simplex virus 2 hsv2 reactivation savoldi et al 2017 eberhardt et al 2004 whalen et al 2019 comorbid neurologic diseases like multiple sclerosis ms can become detrimental confounding factor leading delayed diagnosis management es due preexisting diagnostic bias present case relapsingremitting ms rrms complicated es likely due reactivation latent hsv infection following high immunosuppression presumed refractory ms relapses,0.0
long noncoding rna lncc11orf541 modulates neuroinflammatory responses activating nfb signaling meningitic escherichia coli infection abstractescherichia coli common gramnegative pathogenic bacterium causing meningitis penetrates bloodbrain barrier bbb activates nuclear factor kappa b nfb signaling vital events leading development meningitis long noncoding rnas lncrnas implicated regulating neuroinflammatory signaling previous study showed e coli can induce differential expression lncrnas including lncc11orf541 human brain microvascular endothelial cells hbmecs hbmecs constitute structural functional basis bbb however unclear whether lncrnas involved regulation inflammatory responses hbmecs meningitic e coli infection study characterized abundantly expressed lncrna lncc11orf541 degraded translocated coilin produce mgu219 mgu230 hbmecs e coli infection functionally lncc11orf541originated noncoding rna mgu230 interacted interleukin1 receptorassociated kinase 1 irak1 induce oligomerization autophosphorylation thus promoting activation nfb signaling facilitating production proinflammatory cytokines summary study uncovers involvement lncc11orf541 irak1nfb signaling functions positive regulator inflammatory responses meningitic e coliinduced neuroinflammation may valuable therapeutic diagnostic target bacterial meningitis,0.0
intestinal dysbiosis featuring abundance streptococcus associates henochschnlein purpura nephritis iga vasculitis nephritis adult background pathogenesis henochschnlein purpura nephritis hspn closely associated mucosal infection whether intestinal microbiota dysbiosis plays role clearmethodsa total 52 participants including 26 hspn patients 26 healthy controls included using 16s ribosomal rna gene sequencing intestinal microbiota composition hspn healthy controls compared diagnostic potency evaluated receiver operating characteristic roc area curves auc meanwhile correlation analysis also performedresultsthe lower community richness diversity fecal microbiota displayed hspn patients structure gut microbiota remarkedly different genuslevel comparison indicated significant increase proportions gbacteroides gescherichiashigella gstreptococcus marked reduction gprevotella_9 hspn patients suggesting overrepresentation potential pathogens reduction profitable strains main feature dysbiosis differential taxonomic abundance might make sense distinguishing hspn healthy controls auc 086 relative abundance differential bacteria also concerned clinical indices among streptococcus spp positively associated severity hspn p 0050 found hspn patients higher level streptococcus spp likely suffering hematuria hypoalbuminemia p 0050 conclusionsthe dysbiosis gut microbiota obvious hspn patients intestinal mucosal streptococcal infection distinctive closely related severity,0.0
mendelian randomization study updates effect 25hydroxyvitamin d levels risk multiple sclerosis background observational studies previous mendelian randomization mr studies shown genetically low 25hydroxyvitamin d 25ohd levels associated high susceptibility multiple sclerosis ms present mr study aims update causal estimates effects 25ohd levels ms riskmethodsto date largest genomewide association study gwas serum 25ohd n 401 460 ms 14 498 ms cases 24 091 controls used assess effect serum 25ohd levels ms participants european ancestry mregger_intercept test cochrans q statistic used determine pleiotropy heterogeneity respectively mregger weighted median inverse variance weighted multiplicative random effects simple mode weighted mode methods used evaluate causal association serum 25ohd levels ms finally effect single 25ohd snp single nucleotide polymorphism ms used test snp biasresultsone hundred fifteen newly identified serum 25ohd genetic variants extracted largescale serum 25ohd gwas dataset 20 effective independent 25ohd genetic instrumental variables extracted ms gwas summary statistics pleiotropy analysis suggested significant pleiotropic variant among 20 selected 25ohd genetic instrument variants ms gwas datasets serum levels 25ohd based genetic changes increased risk ms decreased using mregger beta 0940 p 0001 0391 weighted median beta 0835 p 0000 0434 ivw beta 0781 p 0000 0458 simple mode beta 1484 p 0016 0227 weighted mode beta 0913 p 0000 0401 results robust obvious bias based investigating single 25ohd snp msconclusionsour analysis suggested causal association genetically increased serum 25ohd levels reduced ms european population,0.0
injectable versus oral firstline multiple sclerosis therapies knows unknowns observational studies neural regen res 2022 mar 17 3 567568 doi 104103 16735374320985no abstractpmid34380893 doi104103 16735374320985,0.0
oligodendrocyte pathology fetal alcohol spectrum disorders neural regen res 2022 mar 17 3 497502 doi 104103 16735374314294abstractthe pathology fetal alcohol syndrome less severe fetal alcohol spectrum disorders includes brain dysmyelination recent studies shed light molecular mechanisms underlying white matter abnormalities rodent models fetal alcohol syndrome human studies shown suppressed oligodendrocyte differentiation apoptosis oligodendrocyte precursor cells ethanol exposure led reduced expression myelin basic protein delayed myelin basic protein expression rat mouse models fetal alcohol syndrome human histopathological specimens several studies reported increased expression many chemokines dysmyelinating disorders central nervous system including multiple sclerosis fetal alcohol syndrome acute ethanol exposure reduced levels neuroprotective insulinlike growth factor1 fetal maternal sheep human fetal brain tissues ethanol increased expression tumor necrosis factor mouse human neurons white matter lesions induced developing sheep brain alcohol exposure early gestation rat fetal alcohol syndrome models shown reduced axon diameters thinner myelin sheaths well reduced numbers oligodendrocytes also morphologically aberrant oligodendrocytes expressions markers mature myelination including myelin basic protein also reduced accumulating knowledge concerning mechanisms ethanolinduced dysmyelination lead development strategies prevent dysmyelination children exposed ethanol fetal development future studies using fetal oligodendrocyte oligodendrocyte precursor cellderived exosomes isolated mothers blood may identify biomarkers fetal alcohol syndrome even implicate epigenetic changes early development affect oligodendrocyte precursor cell oligodendrocyte function adulthood combining various imaging modalities molecular studies may possible determine fetuses risk intervene therapeutically early pregnancypmid34380877 doi104103 16735374314294,1.0
il17 crosses bloodbrain barrier trigger neuroinflammation novel mechanism nitroglycerininduced chronic migraine background chronic migraine places disabling burden patients extensively modeled nitroglycerin ntg treated animal model although nfb pathway involved increase cgrp levels activation trigeminal system ntg model relationship ntg neuroinflammation remains unclear study aimed optimize chronic ntg rat model hyperalgesia ethological capacity estimating migraine therapies explore underlying mechanism ntginduced migrainemethodsrats administered different doses ntg sc daily every 2 d 30 min 2 h later mechanical threshold tested 9 d rats injected eb cy55 permeability assay animals sacrificed brainstem caudal trigeminal ganglion removed test cgrp cfos nos activity cytokines levels tissue serum measured elisa nfb pathway bloodbrain barrier bbb related indicators analyzed using western blotting immunohistochemistry performed observe microglial polarization il17a+ t cell migration medulla oblongataresultsntg 10 mg kg sc every 2 d total 5 injections optimal condition resulting progressive hyperalgesia migraine behavior tnc neuroinflammation increases cytokines cgrp cfos activation nfb pathway observed changes alleviated ibuprofen furthermore ntg administration increased bbb permeability altering levels functional proteins rage lrp1 aqp4 mfsd2a structural proteins zo1 occludin vecadherin2 increase peripheral il17a permeation medulla oblongata activating microglia neuroinflammation eventually causing hyperalgesia migraine attackconclusionsthis study confirmed ntg 10 mg kg sc every 2 d total 5 injections optimal condition provoke migraine resulting mechanical hyperalgesia observable migrainelike behavior furthermore il17a crossed bloodbrain barrier medulla oblongata triggering tnc activation microgliamediated neuroinflammation process novel mechanism ntginduced chronic migraine suggesting il17a might novel target treatment migraine,0.0
hydroxychloroquine administration exacerbates acute kidney injury complicated lupus nephritis background hydroxychloroquine hcq recommended basic treatment lupus nephritis ln decade based ability improve lnrelated renal immunemediated inflammatory lesions classical lysosomal inhibitor hcq may inhibit lysosomal degradation disrupt protective autophagy proximal tubular epithelial cells ptecs therefore final renal effects hcq ln need clarifiedmethodhcq administered spontaneous female mrl lpr ln mice severe proteinuria daily 4 weeks moreover mrl lpr mice proteinuric ln subjected cisplatininduced unilateral ischemia reperfusion r induced acute kidney injury aki 2 weeks hcq preadministrationresultsas expected hcq treatment increased survival ratio downregulated levels serum creatinine mice ln ameliorated renal lesions inhibited renal interstitial inflammation unexpectedly hcq preadministration significantly increased susceptibility delayed recovery aki complicated ln demonstrated increase ptec apoptosis expression tubular injury marker kim1 well retardation ptec replenishment hcq preadministration suppressed proliferation ptecs arresting cells g1 s phase upregulated expression cell cycle inhibitors furthermore hcq preadministration disrupted ptec autophagylysosomal pathway accelerated ptec senescenceconclusionhcq treatment may increase susceptibility delay recovery aki complicated ln despite ability improve lnrelated renal immunemediated inflammatory lesions probable mechanism involves accelerated apoptosis inhibited proliferation ptecs via autophagylysosomal pathway disruption senescence promotion,0.0
drug library screen identifies inhibitors toxic astrogliosis abstractbackground multiple sclerosis ms chronic neuroinflammatory disorder activated immune cells directly indirectly induce demyelination axonal degradation inflammatory stimuli also change phenotype astrocytes making neurotoxic resulting toxic astrocytenull phenotype observed animal models neuroinflammation ms lesions proteins secreted toxic astrocytes elevated cerebrospinal fluid csf ms patients reproducibly correlate rates accumulation neurological disability brain atrophy suggests pathogenic role neurotoxic astrocytes msmethods applied commercially available library small molecules either food drug administrationapproved clinical development vitro model toxic astrogliosis identify drugs signaling pathways inhibit inflammatory transformation astrocytes neurotoxic phenotyperesults inhibitors three pathways related endoplasmic reticulum stress 1 proteasome 2 heat shock protein 90 3 mammalian target rapamycin reproducibly decreased inflammationinduced conversion astrocytes toxic phenotype dantrolene antispasticity drug inhibits calcium release ryanodine receptors expressed endoplasmic reticulum central nervous system cells also exerted inhibitory effect vivo achievable concentrations finally established csf serpina3 relevant pharmacodynamic marker inhibiting toxic astrocytes clinical trialsconclusion drug library screening provides mechanistic insight generation toxic astrocytes identifies candidates immediate proofofprinciple clinical trial s,1.0
monitoring safety effectiveness cladribine multiple sclerosis patients 50 years abstractclinical trial data regarding efficacy safety cladribine ms limited young individuals overall riskbenefit profile necessarily applies elderly patients investigated effectiveness safety outcomes ms patients initiating cladribine 50 years n35 50 years n62 median followup 124 months differences time evidence disease activity hr073 95ci018291 p0657 posttreatment lymphocyte counts 024 p0825 occurrence adverse events or084 95ci024293 p0791 age groups female sex greater disability associated higher risk adverse events especially infections limited data suggest safety concerns regarding use cladribine elderly ms,0.0
demand low supply pipeline personalized integrative medicine multiple sclerosis summarytimely personalized medicine unmet critical need multiple sclerosis ms major barrier providing individualized care lack information interventions appropriate viewpoint submit rationale threestep roadmap personalized integrative medicine multidisciplinary team approach requires 1 comprehensively assess whole health diagnosis 2 appropriately integrate data within electronic health record systems leverage machine learning analyze big data 3 design test deliver multimodal interventions using wholeperson approach assessment intervention will better informed provide personalized care level individual,0.0
surviving global pandemic experience depression anxiety loneliness among individuals multiple sclerosis abstractbackgroundthe world experiencing one significant worldwide health pandemics modern history result increased depression anxiety loneliness general population however populations demonstrated prepandemic emotional disturbance social isolation individuals multiple sclerosis ms likely uniquely vulnerable symptomsobjectivethe purpose present investigation examine emotional outcomes including reports loneliness individuals ms covid19 pandemic additionally sought examine individuals experiences pandemic may contribute specific covid19related depression anxietymethods142 individuals ms previously participated national online surveybased study asked complete online survey assessing current level depression anxiety loneliness perceived impact covid19 pandemicresultsincreases rates depression anxiety noted approximately 54 33 reporting new depression anxiety respectively given increase examined individuals new depression anxiety differed without depression anxiety prepandemic depression anxiety significant differences personspecific factors eg personality selfefficacy noted groups increased loneliness also found among depression anxiety regardless whether new prepandemic finally depressed anxious reported greater disruption distress related covid19 pandemic trend increased anxiety specifically related pandemic eg fear dying due covid19 among new depression anxiety compared existing depression anxiety suggesting influence pandemic specific reports new depression anxietyconclusionfindings suggest increased depression anxiety loneliness among individuals ms following covid19 pandemic reports new depression anxiety appears related pandemic specifically moreover factors commonly associated depression anxiety ms eg personality selfefficacy common among existing depression anxiety among experiencing new depression anxiety differences considered attempting ameliorate impact covid19 among experiencing emotional distress,0.0
economic burden multiple sclerosis crosssectional study iran background multiple sclerosis ms chronic debilitating disease imposes heavy socioeconomic burden societies study aimed determine economic burden ms patients using first cinnovex recigen second fingolimod natalizumab drug therapy linesmethodsthis cost illness study economic evaluation carried crosssectional research 2019 southern iran total 259 patients enrolled two lines drug therapy 178 patients first line 81 ones second prevalencebased approach bottomup approach used collect cost information calculate costs societal perspective respectively human capital approach applied calculate indirect costs collect required data researchermade data collection form utilized data obtained using information available patients medical records insurance invoices well selfreports companionsresultsthe results showed annual costs ms first second lines drug therapy per patient 1919 4082 purchasing power parity ppp respectively total 2721 ppp 2019 highest mean costs lines direct medical costs purchasing main medicines lines accounted highestconclusionconsidering findings study order reduce burden disease following suggestions presented providing necessary facilities production ms drugs country proper equitable distribution neurologists expanding provision home care services using technologies related internet including whatsapp follow ms patients treatment,0.0
unraveling complex interplay genes environment climate als ebiomedicine 2021 dec 30 75103795 doi 101016 jebiom2021103795 online ahead printabstractvarious genetic environmental risk factors implicated pathogenesis amyotrophic lateral sclerosis als despite cause als cases remains obscure review describe current evidence implicating genetic environmental factors motor neuron degeneration risk exerted many environmental factors may appear small effect magnified presence genetic predisposition postulate geneenvironment interactions account least portion unknown etiology als climate underlies multiple environmental factors implied als etiology impact global temperature increase geneenvironment interactions carefully monitored describe main concepts underlying interactions although lack large cohorts detailed genetic environmental information hampers search geneenvironment interactions newer algorithms machine learning approaches offer opportunity break stalemate understanding genetic environmental factors interact cause als may ultimately pave way towards precision medicine becoming integral part als carepmid34974309 doi101016 jebiom2021103795,0.0
mir125a5p attenuates macrophagemediated vascular dysfunction targeting ninjurin1 cell death differ 2022 jan 1 doi 101038 s4141802100911y online ahead printabstractninjurin1 ninj1 adhesion molecule regulates macrophage function hyaloid regression multiple sclerosis atherosclerosis however biological relevance mechanism underlying function vascular network integrity studied study investigated role ninj1 physiological postnatal vessel formation pathological endotoxinmediated inflammation diabetes conditions developed strategy regulate ninj1 using specific micro mi rnas pathological conditions ninj1deficient mice exhibited decreased hyaloid regression tip cell formation retinal vascularized area recruitment macrophages endothelial apoptosis postnatal development resulting delayed formation vascular network five putative mirnas targeting ninj1 selected using miranda algorithm comparison expression patterns among mir125a5p showed profound inhibitory effect ninj1 expression mir125a5p mimic suppressed celltocell celltomatrix adhesion macrophages expression proinflammatory factors mediated ninj1 furthermore mir125a5p mimic inhibited recruitment macrophages inflamed retinas endotoxininduced inflammation streptozotocininduced diabetes vivo particular mir125a5p mimic significantly attenuated vascular leakage diabetic retinopathy taken together findings suggest ninj1 plays pivotal role macrophagemediated vascular integrity mir125a5p acts novel regulator ninj1 management inflammatory diseases diabetic retinopathypmid34974535 doi101038 s4141802100911y,0.0
auditory evoked potentials children adolescents multiple sclerosis neuromyelitis optica spectrum disorders int j pediatr otorhinolaryngol 2021 dec 28 153111013 doi 101016 jijporl2021111013 online ahead printabstractbackground children acute demyelinating disease may evolve multiphasic disease multiple relapses multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd brainstem auditory evoked potentials baep longlatency auditory evoked potentials llaep contribute identification either retrocochlear changes central auditory nervous system cans changesobjectives characterize baep llaep children adolescents ms nmosd verify diagnostic values potentials demyelinating diseasesmethods 40 participants divided two study groups sg1 ms sg2 nmosd two comparison groups cg1 cg2 matched age 9 years17 years 11 months sex electrophysiological hearing assessment performed baep llaepresults sg1 sg2 compared cg1 cg2 regarding baep llaep sg1 sg2 presented higher occurrence changes also individuals ms higher occurrences baep changes whereas individuals nmosd higher occurrence llaep changesconclusions baep llaep children adolescents ms nmosd showed higher latencies lower amplitudes components individuals compared peers procedures highly accurate identify demyelinating diseases baep results abnormal individuals ms llaep nmosd findings indicate auditory evoked potentials important instruments differential diagnosis ms nmosd valuable monitor disease evolutionpmid34974278 doi101016 jijporl2021111013,1.0
atherosclerosis multiple sclerosis overview prevalence risk factors abstractbackground atherosclerosis leading cause ischemic heart disease coronary artery disease process atherosclerosis develops period years mainly immunemediated data regarding prevalence vascular disease atherosclerosis among people multiple sclerosis pwms inconsistent therefore aimed provide overview prevalence atherosclerotic risk factors pwmsmethods crosssectional study period one year among pwms visiting isfahan ms center study data extracted using participantsnull files checklist completed observers people relapsingremitting rrms secondary progressive spms forms ms included study participants primary progressive ppms disease described excluded analysesresults 396 pwms 343 rrms 53 spms descending order reported risk factors tobacco smoking 184 dyslipidemia 10 hypertension 88 diabetes mellitus 45 people rrms 174 smokers 99 dyslipidemia 81 hypertension 43 diabetes mellitus spms patients 245 reported history smoking 132 hypertension 94 dyslipidemia 37 diabetes mellitus smoking insignificantly associated higher expanded disability status scale z 170 pvalue0090 male sex rr 95ci 1628 1172 2261 pvalue004 increasing age rr 95ci 1024 1008 1040 pvalue003 associated higher number risk factorsconclusion highest observed atherosclerosis risk factor among pwms smoking diabetes mellitus least reported risk factor population whole overall participants rrms dyslipidemia hypertension second third commonly reported risk factors however hypertension exceeded dyslipidemia participants spms male sex increasing age associated higher number atherosclerosis risk factors,0.0
social determinants health neurology neurol clin 2022 feb 40 1 231247 doi 101016 jncl202108012abstractneurologic health disparities created perpetuated structural social determinants health factors include limited interpersonal bias institutional factors lead disparate access care neighborhoodlevel factors socioeconomic status segregation access healthy food effects determinants health can seen throughout neurology including stroke epilepsy headache amyotrophic lateral sclerosis multiple sclerosis dementia interventions improve neurologic health equity require multilayered approaches address interdependent factors create perpetuate disparate neurologic health access outcomespmid34798972 doi101016 jncl202108012,0.0
difference radiologic outcomes natalizumab patients treated extended interval dosing compared standard interval dosing realworld evidence ms paths abstractbackground extended interval dosing eid average dosing interval approximately every 6 weeks natalizumab associated significantly lower risk progressive multifocal leukoencephalopathy standard interval dosing sid every 4 weeks patients relapsingremitting multiple sclerosis ms realworld studies though limited suggest natalizumab effectiveness generally maintained patients switch eid initiation stable treatment sid ms paths multiple sclerosis partners advancing technology health solutions collaborative multicenter learning health system generates realworld clinical mri data using highly standardized acquisition protocols compared mri outcomes ms paths patients treated natalizumab eid versus sid also compared mri outcomes patients treated natalizumab eid sid versus injectable ms platform therapymethods natalizumab infusion data touch prescribing program database ms paths mri assessment data seven us sites july 23 2020 used identify patients relapsingremitting ms received natalizumab eid sid interval two mri scans mri segment patients received injectable platform ms therapy two mri scans also identified mri data used determine incidence rate odds developing new enlarging t2 lesions annualized percentage change t2 lesion volume t2lv annualized percentage change brain parenchymal fraction bpf mri outcomes compared 1 natalizumab eid treatment versus natalizumab sid treatment 2 natalizumab treatment eid+sid versus platform therapy 3 natalizumab eid versus platform therapy propensity scorebased weighting matching used balance covariates start mri segments comparisonsresults mri outcomes observed natalizumab eid treatment differ significantly observed natalizumab sid treatment odds ratio new enlarging t2 lesion 107 95 confidence interval ci 093 124 p0355 rate ratio 95 ci new enlarging t2 lesions 162 093 282 p0090 differences 95 ci eid sid patients mean annualized percentage change t2lv bpf 156 377 690 p0566 011 025 010 p0096 respectively conversely mri outcomes natalizumab platform therapy patients compared significant differences favoring natalizumab assessments odds new enlarging t2 lesion odds ratio 069 95 ci 064 075 p0001 incidence rate new enlarging t2 lesions rate ratio 047 95 ci 037 061 p0001 annualized percentage change decrease t2lv difference 368 95 ci 706 030 p0033 annualized percentage change increase bpf difference 022 95 ci 016 029 p0001 results subgroup comparison natalizumab eid patients platform therapy patients similar overallnatalizumabgroupversusplatformtherapy comparisonconclusions results indicate natalizumab eid sid provide comparable realworld effectiveness quantitative mri metrics data demonstrate natalizumab eid can provide superior realworld effectiveness injectable platform therapy quantitative mri metrics,0.0
real world comparison teriflunomide dimethyl fumarate nave relapsing multiple sclerosis patients evidence italian ms register abstractbackgroundteriflunomide teri dimethyl fumarate dmf licensed firstline diseasemodifying treatments dmts relapsing remitting multiple sclerosis rrms largely replacing injectable dmtsmethodsall rrms patients starting teri dmf january 1 2013 december 31 2017 included analysis time first relapse time confirmed disability progression cdp time dmt discontinuation investigated propensity score inverse probability treatment weighting iptwps used adjust comparisons baseline confounders aim study compare effectiveness rate discontinuation dmf teri first therapeutic choice italian ms registerresultsa total 683 patients considered analyses 185 teri 498 dmfpatients teri higher number relapses 2314 vs 1911 p033 higher baseline disability level assessed expanded disability status scale edss 20 interquartile rangeiqr 1030 vs 15 iqr 1020 p013 iptw adjusted cox models reveal difference investigated dmts investigated outcomesconclusionsteri dmf similar effectiveness rate discontinuation employed first therapeutic choice rrms patients,0.0
selfsupervised ivim dwi parameter estimation physics based forward model magn reson med 2021 oct 22 doi 101002 mrm28989 online ahead printabstractpurpose assess robustness repeatability intravoxel incoherent motion model ivim parameter estimation diffusionweighted mri abdominal organs constraints noisy diffusion signal using novel neural network methodmethods clinically acquired abdominal scans crohns disease patients retrospectively analyzed regions segmented kidney cortex spleen liver bowel novel ivim parameter fitting method based principle physics guided selfsupervised convolutional neural network require reference parameter estimates training compared conventional nonlinear least squares nnls algorithm voxelwise trained artificial neural network ann results results showed substantial increase parameter robustness noise corrupted signal intrasession repeatability experiment proposed method showed reduced coefficient variation cov multiple acquisitions comparison conventional nlls method comparable performance ann use d f estimates proposed method led smallest misclassification error linear discriminant analysis characterization normal abnormal crohns disease bowel tissue fitting d parameter remains challengingconclusion proposed method yields robust estimates d f ivim parameters constraints noisy diffusion signal indicates potential use proposed method conjunction accelerated dwmri acquisition strategies typically result lower signal noise ratiopmid34687065 doi101002 mrm28989,0.0
recombinant hepatitis b vaccine uptake multiple sclerosis risk marginal structural modeling approach abstractbackgroundthere ongoing debate regarding association uptake recombinant vaccine hepatitis b virus hbv multiple sclerosis ms risk casecontrol study tested hypothesis whether recombinant hbv vaccination status causally associated ms risk using targeted maximum likelihood estimation tmle techniquemethodsconfirmed 110 ms cases age 5 years gender nativity matched 11 110 controls enrolled data collected demographics environmental factors history vaccinations past morbidities facetoface interview cases controls estimate causal parameters including marginal odds ratio causal relative risk rr causal risk difference rd 95 confidence intervals cis implemented casecontrolweighted tmle matched design uses dataadaptive flexible stacked ensemblebased machine learning system namely super learner additionally population preventable fraction ppf ms risk computedresultsthis study demonstrated significant nonspecific protective effect hbv vaccination ms risk marginal 044 95 ci 019068 p0006 causal rr 064 95 ci 046089 p0004 significant causal rd showed among vaccinated 19 fewer ms cases occurred owing hbv vaccination causal rd 019 95 ci 032 006 p0014 source population vaccination hbv led 174 reduced ms risk ppf174 95 ci 38 363 conclusionthe results suggest significant nonspecific protective effect recombinant hbv vaccine ms risk future studies may contemplate confirm results,0.0
diagnosis management central nervous system demyelinating disorders neurol clin 2022 feb 40 1 113131 doi 101016 jncl202108008abstractthe spectrum demyelinating diseases affecting central nervous system broad although many chronic course neuroinflammatory conditions often present acute subacute onset symptoms requiring hospitalization severe article reviews acute phase assessment management disorders particular focus multiple sclerosis neuromyelitis optica spectrum disorder myelin oligodendrocyte glycoprotein antibody disorder several atypical demyelinating diseasespmid34798965 doi101016 jncl202108008,1.0
evaluation times disability progression related factors patients primary progressive multiple sclerosis argentina abstractbackground ppms primary progressive multiple sclerosis patients represent less 10 ms patients argentina men women similarly affected severe functional impairment rapid progression reported males case datasets main objective study determine time edss expanded disability status scale 4 6 7 ppms patients also compared times reach edss men women aimed identify factors associated disability progressionmethod cohort patients diagnosis ppms n253 selected followup recorded relevarem registry databaseresult median times edss 4 6 7 24 iqr 1248 72 iqr 3696 96 iqr 60120 months respectively comparison survival curves edss 4 6 7 according gender show significant differences p033 p055 p059 evidence association clinical adjustment variables sex age 40 years diagnosis edss 3 onset multifocal ms symptoms disease onset time arrival edss 4 6 7conclusion severe disability observed six years onset symptoms association found studied factors time arrival severe disability,0.0
deep brain stimulation use treating multiple sclerosis tremor practical approach metaanalyses summarydeep brain stimulation dbs introduced treatment option multiple sclerosis ms related tremor recent emerging studies investigated efficacy safety yet study systematically assessed evidence topic zali colleagues conducted first systematic review metaanalysis use dbs ms tremor patients letter highlight points metaanalysis regarding high heterogeneity levels reflect methodological concerns related pooling studies considerable variability also suggest approaches address problem,0.0
datadriven t 2 relaxation analysis approach myelin water imaging spectrum analysis multiple exponentials via experimental condition oriented simulation sameecos magn reson med 2021 sep 7 doi 101002 mrm29000 online ahead printabstractpurpose decomposition multiexponential decay data t2 spectrum poses substantial challenges conventional fitting algorithms including nonnegative least squares nnls based combination resolution limit constraint machine learning neural network algorithm datadriven highly tailorable analysis method named spectrum analysis multiple exponentials via experimental condition oriented simulation sameecos proposedtheory methods theory sameecos derived paradigm presented demonstrate sameecos workflow consisting series calculation simulation model training operations performance trained sameecos model evaluated using simulations six vivo brain datasets code available https githubcom hanwencat sameecosresults using nnls baseline sameecos achieved 15 higher overall cosine similarity scores producing t2 spectrum 10 lower mean absolute error calculating myelin water fraction mwf well demonstrated better robustness noise simulation tests applying vivo data mwf sameecos nnls highly correlated among study participants however distinct separation myelin water peak intra extracellular water peak observed mean t2 spectra determined using sameecos terms data processing speed sameecos approximately 30 times faster nnls achieving wholebrain analysis 3 minconclusion compared nnls sameecos method yields much reliable t2 spectra dramatically shorter time increasing feasibility multicomponent t2 decay analysis clinical settingspmid34490909 doi101002 mrm29000,1.0
recovering swifiltered phase data using deep learning magn reson med 2021 oct 5 doi 101002 mrm29013 online ahead printabstractpurpose develop deep neural network recover filtered phase clinical mr phase images enable computation qsmsmethods eighteen deep learning networks trained recover combinations 13 swi phasefiltering pipelines swifiltered data computed offline five multiorientation multiecho mri scans yielding 132 3d volumes 118 7 7 training validation testing two experiments conducted show efficacy networks first using qsm processing local fields computed raw phase subsequently filtered using swifiltering pipelines networks trained invert filtering operation second trained networks finetuned recover unfiltered local fields filtered local fields computed applying qsm processing swifiltered phase susceptibility maps computed recovered fields compared gold standard multiple orientation sampling reconstructionsresults susceptibility maps computed raw phase using standard qsm processing normalized root mean square error nrmse 0732 0095 susceptibility maps computed recovered phase obtained nrmses 0725 0095 network trained using 13 processing methods generalized well obtaining nrmses 0725 089 filters seen matching reconstruction accuracy networks trained recover single filterconclusion feasible recover swifiltered phase using deep learning qsm can computed recovered phase swi acquisition comparable accuracy standard qsm processingpmid34611931 doi101002 mrm29013,0.0
nmyc downstream regulated family member 1 ndrg1 enriched myelinating oligodendrocytes impacts myelin degradation response demyelination glia 2021 oct 23 doi 101002 glia24108 online ahead printabstractthe nmyc downstream regulated gene family member 1 ndrg1 gene whose mutation results peripheral neuropathy central manifestations previous studies characterized ndrg1 role schwann cells detection central nervous system symptoms identification ndrg1 gene silenced white matter multiple sclerosis brains raise question regarding role oligodendrocytes show ndrg1 enriched oligodendrocytes myelin preparations characterize expression using novel reporter mouse tgndrg1egfp report ndrg1 expression developmental myelination remyelination cuprizoneinduced demyelination adult corpus callosum transcriptome ndrg1egfp+ cells supports identification late myelinating oligodendrocytes characterized expression genes regulating lipid metabolism bioenergetics also generate lineage specific conditional knockout olig1cre + ndrg1fl fl line study function null mice develop normally despite similar numbers progenitor cells wild type fewer mature oligodendrocytes lower levels myelin proteins controls thereby suggesting ndrg1 important maintenance late myelinating oligodendrocytes addition control ndrg1 null mice subject cuprizoneinduced demyelination observe higher degree demyelination mutants together data identify ndrg1 important molecule adult myelinating oligodendrocytes whose decreased levels normal appearing white matter human ms brains may result greater susceptibility myelin damagepmid34687571 doi101002 glia24108,1.0
complete pathologic response pembrolizumab axitinib patient sarcomatoid rcc ocrelizumabtreated multiple sclerosis urology 2021 dec 29s00904295 21 011869 doi 101016 jurology202112015 online ahead printabstractnonclear cell renal cell carcinoma rcc heterogeneous disease report case sarcomatoid nonclear cell rcc patient underlying multiple sclerosis ms immunosuppression complete pathologic response pembrolizumab axitinib comprehensive genomic profiling revealed pathogenic mutations setd2 tp53 high rna expression levels immune checkpoint proteins case illustrates importance treatment selection based presence sarcomatoid features underlying autoimmune disease genomic profilingpmid34973243 doi101016 jurology202112015,0.0
perspective persistent toxicants veterans amyotrophic lateral sclerosis identifying exposures determining higher als risk j neurol 2022 jan 1 doi 101007 s00415021109285 online ahead printabstractmultiple studies indicate united states veterans increased risk developing amyotrophic lateral sclerosis als compared civilians however responsible etiological factors unknown general population specific occupational eg truck drivers airline pilots environmental exposures eg metals pesticides associated increased als risk increased prevalence als veterans strongly suggests exposures experienced military personnel disproportionate civilians service veterans may encounter numerous neurotoxic exposures eg burn pits engine exhaust firing ranges far however paucity studies investigating environmental factors contributing als veterans even fewer assessing exposure using biomarkers herein discuss als pathogenesis relation series persistent neurotoxicants often emitted mixtures including chemical elements nanoparticles lipophilic toxicants dioxins polycyclic aromatic hydrocarbons polychlorinated biphenyls propose toxicants directly measured veteran central nervous system tissue may accumulated decades specific toxicants mixtures thereof may accelerate als development following multistep hypothesis act synergistically servicelinked exposures eg head trauma concussions possibilities explain lower age onset observed veterans compared civilians identifying highrisk exposures within vulnerable populations key understanding als etiopathogenesis urgently needed act upon modifiable risk factors military personnel deserve enhanced protection years service shortterm also longterm healthpmid34973105 doi101007 s00415021109285,0.0
burden carers multiple sclerosis adv exp med biol 2021 1337169175 doi 101007 9783030787714_19abstractbackground family members patients multiple sclerosis ms called become carers playing vital difficult role supporting patients daily life aim study investigate extent multidimensional burden carers multiple sclerosismethods data collected 111 carers ms patients survey conducted patras general hospitalresults according research findings multidimensional burden carers proportional severity patients condition particular majority patients good kinetic state carers examined felt gentle moderate burden scales zarit bakas observed age caregiver type care provides patients dependence increase feeling burden positive results care improve caregivers relationship patient selfesteem ability cope stress according fcopes scale observed relationship caregiver patient responsible accepting problem greater caregivers age higher percentage seeking help doctors social servicesconclusions burden carers indisputable support family members social economic support education may mitigate burden carepmid34972903 doi101007 9783030787714_19,0.0
newly intervention strategy preeclampsia targeting pd1 tim3 signaling pathways modulate polarization decidual macrophages abstractprogrammed cell death1 pd1 tcell immunoglobulin mucin3 tim3 important immune checkpoint receptors prevent overreacted maternal immune response fetal antigens pregnancy disruption complex immune regulation mechanisms associated adverse pregnancy outcomes including preeclampsia pe recent study showed tim3 pathway involved regulation decidual macrophage polarization decidual macrophages polarized m1 phenotype may impair uterine vessel remodeling placentation accounting occurrence pe coblockade pd1 tim3 pathway shown successfully control tumor growth preclinical cancer models however effects activating pd1 tim3 pathways combined intervention strategy pe never reported herein observed skew decidual macrophage polarization toward m1 phenotype patients pe lipopolysaccharide lps induced pelike rat model moreover found activation pd1 tim3 pathway using pdl1 gal9 fusion proteins alleviate manifestation lpsinduced pelike rats protect offspring compared single intervention combination pdl1and gal9 fusion proteins exhibited obvious advantages relief pelike symptoms trophoblast invasion fetal vascular development indicating synergistic effect activated pd1 tim3 pathway vitro study also revealed combined intervention using pdl1 gal9 fusion proteins inhibited lpsinduced m1macrophage polarization via synergic activation erk gsk3 catenin signaling pathway together findings provide first evidence simultaneous activation pd1 tim3signaling pathways may optimal protective effect serve new potential target pe intervention,0.0
lipid scavenging macrophages inflammation biochim biophys acta mol cell biol lipids 2021 oct 6159066 doi 101016 jbbalip2021159066 online ahead printabstractmacrophages professional phagocytes indispensable maintenance tissue homeostasis integrity depending resident tissue macrophages exposed highly diverse metabolic environments adapted niche can contribute local metabolic turnover metabolite uptake conversion storage release disturbances tissue homeostasis caused infection inflammation damage dramatically alter local milieu impacting macrophage activation status metabolism case persisting stimuli defective macrophage responses ensue can promote tissue damage disease especially relevant herein disbalances lipid rich environments macrophages crucially involved lipid uptake turnover preventing lipotoxicity lipid uptake large extent facilitated macrophage expressed scavenger receptors dynamically regulated important many metabolic diseases review receptors mediating lipid uptake summarize recent findings role health disease highlight underlying pathways driving macrophage lipid acquisition impact myeloid metabolic remodellingpmid34626791 doi101016 jbbalip2021159066,0.0
culturing expansion quot clinical gradequot neural stem cells fetal human central nervous system methods mol biol 2022 23895766 doi 101007 9781071617830_5abstractnscs demonstrated useful grafts mammalian central nervous system investigate exploitation nsc therapy neurodegenerative disorders animal models neurodegenerative diseases push cell therapy cns stage clinical application necessary establish continuous standardized clinical grade ie produced following good manufacturing practice guidelines human neural stem cell linesin chapter will illustrate protocols production characterization routinely used gmp cell factory production clinical grade human neural stem cell lines already use clinical trials neurodegenerative diseases particularly amyotrophic lateral sclerosis als clinicaltrialsgov number nct01640067 secondary progressive multiple sclerosis spms clinicaltrialsgov number nct03282760 pmid34558001 doi101007 9781071617830_5,0.0
enhanced remyelination transthyretin null mice following cuprizone mediated demyelination neurosci lett 2021 oct 8136287 doi 101016 jneulet2021136287 online ahead printabstractthyroid hormones ths impact nearly every tissue body including adult developing central nervous system distribution ths around body facilitated specific th distributor proteins including transthyretin ttr addition produced liver ttr synthesized choroid plexus brain synthesis ttr choroid plexus epithelial cells allows transport ths blood brain adequate supply ths brain required developmental myelination axons maintenance mature myelin throughout adult life essential proper conduction nerve impulses insufficient ths developing mice results hypomyelination thinner myelin around axons however confounding evidence demonstrated developing brains ttr null mice hypermyelination axons observed corpus callosum raised question whether increased myelination occurs remyelination adult brain following targeted demyelination investigate effect ttr remyelination cuprizone induced depletion myelin corpus callosum adult mice initiated followed period myelin repair myelin thickness measured assess remyelination rates 6 weeks ttr null mice displayed expedited rates early remyelination preferentially remyelinating smaller axons compared wild type mice furthermore ttr null mice produced thicker myelin wild type mice remyelination results may broader implications understanding mechanisms governing remyelination particularly potential therapeutic contexts acquired demyelinating diseases multiple sclerosispmid34634393 doi101016 jneulet2021136287,1.0
immunomodulatory functions trpm7 implications autoimmune diseases immunology 2021 sep 24 doi 101111 imm13420 online ahead printabstractautoimamune disease inappropriate response ones tissues due break immune tolerance exposure selfantigens often leads structural functional damage organs well systemic disorders date effective interventions prevent progression autoimmune diseases hence urgent need new treatment targets trpm7 enzymecoupled transient receptor ion channel subfamily m plays vital role pathologic physiologic conditions trpm7 constitutively activated certain conditions can regulate cell migration polarization proliferation cytokine secretion however growing body evidence highlights critical role trpm7 autoimmune diseases including rheumatoid arthritis multiple sclerosis diabetes herein present review channel kinase properties trpm7 pharmacological properties b discuss role trpm7 immune cells neutrophils macrophages lymphocytes mast cells upstream immunoreactive substances c highlight trpm7 potential therapeutic target autoimmune diseasespmid34558663 doi101111 imm13420,0.0
computer analysis relation hydrogen bond stability sod1 mutants survival time amyotrophic lateral sclerosis patients j mol graph model 2021 oct 6 110108026 doi 101016 jjmgm2021108026 online ahead printabstractbackground objective mutations sod1 protein can lead death motor neurons turn causes incurable disease called amyotrophic lateral sclerosis als time mechanism onset development disease fully understood often contradictorymethods accelerated molecular dynamics implemented openmm library principal component analysis regression analysis random forest methodresults stability hydrogen bonds 72 mutants sod1 protein calculated principal component analysis carried based ten principal components acting predictors multiple linear regression model constructed analysis correlation ten principal components initial values stability hydrogen bonds made possible characterize contribution known structurally functionally important sites sod1 scatter als patients survival timeconclusion analysis made possible put forward hypotheses relationship stabilizing destabilizing effects mutations different structurally functionally important regions sod1 patientss survival timepmid34653813 doi101016 jjmgm2021108026,0.0
diagnostic therapeutic assistance pathway amyotrophic lateral sclerosis northeastern italian region satisfaction patients caregivers health soc care community 2021 may 20 doi 101111 hsc13379 online ahead printabstractin order evaluate users satisfaction degree diagnostic therapeutic assistance services amyotrophic lateral sclerosis als italian region friulivenezia giulia fvg selfcompiled anonymous multiplechoice questionnaire administered als patients caregivers questionnaire explored 41 different issues covering following areas access diagnostic pathway communication among patients families health professionals b quality disease monitoring effectiveness interventions aimed mitigating als symptoms c easiness access assistive devices eg wheelchair anklefootorthosis home assistance d patient choices sharing health professionals empathy issues proposed patients carers appropriately adapting questions period june december 2019 answers categorised according criticality level median interquartile range numeric variables percentages categorical variables answers questions calculated mean percentage satisfied users 728 considering areas pain treatment easiness access ambulance transport positive aspects 957 925 satisfied respondents respectively information possible enrolment clinical trials possible registration regional als association critical issues 309 434 satisfied users although satisfaction level als patients caregivers services provided resulted generally good areas improved purpose enhancement multidisciplinary collaboration sharing points view users different practitioners rising awareness among healthcare professionals clinical audits useful research needed identify wider range users unexplored unmet needspmid34014000 doi101111 hsc13379,0.0
treatment multiple sclerosis fatigue synthetic psychoactive drug modafinil exp neurol 2021 oct 25113906 doi 101016 jexpneurol2021113906 online ahead printabstractmultiple sclerosis ms complex disorder characterized broad spectrum symptoms evolve throughout disease symptoms can categorized visible invisible based external sight recognition however although others poorly recognize invisible symptoms mood dysfunction neuropathic pain fatigue can significantly affect activities daily living quality life people ms pwms pwms frequently complain fatigue physical cognitive manifestations fatigue ms improve resolve rest disproportionate respect exerted effort fatigue management ms challenging pharmacological approaches successfully proposed among drug modafinil attracted attention properties synthetic psychoactive drug review focus evidence available date supporting use modafinil ms fatigue however despite availability trials evaluating effects modafinil fatigue contrasting results failed support usefulness fatigue management mspmid34710403 doi101016 jexpneurol2021113906,1.0
editorial quot longitudinal sodium mri multiple sclerosis lesions added value sodium inversion recovery mriquot j magn reson imaging 2021 jul 29 doi 101002 jmri27872 online ahead printno abstractpmid34327746 doi101002 jmri27872,0.0
editorial quot unraveling mribased microstructural signatures behind primary progressive relapsingremitting multiple sclerosis phenotypesquot j magn reson imaging 2021 jul 23 doi 101002 jmri27862 online ahead printno abstractpmid34296789 doi101002 jmri27862,0.0
realworld study alemtuzumab cohort italian patients eur j neurol 2021 sep 24 doi 101111 ene15121 online ahead printabstractbackground realworld data alemtuzumab limited provide evidence effectiveness different disease modifying therapies dmts aim provide realworld data impact clinical variables previous dmts clinical response alemtuzumabmethods sixteen italian mscenters retrospectively included patients started alemtuzumab january 2015 december 2018 recorded demographics previous therapies washout duration relapses edss mri data negativebinomial regression models used assess effect factors annualized relapse rate arr alemtuzumab initiationresults studied 322 patients mean age 368 years median edss 3 median followup 194 years previous treatments fingolimod 106 natalizumab 80 firstline orals 56 firstline injectables ifn ga 30 drugs 15 thirtyfive patients treatmentnave prealemtuzumab arr 099 decreased 013 alemtuzumab p0001 number previous year relapses associated alemtuzumabarr adjusted rr138 p0009 progressionfree survival 945 one 892 two years alemtuzumab edss improvement occurred 135 one 206 two years rebaselining patients 6 months alemtuzumab treatment led neda status 716 1 year 589 2 yearsconclusions alemtuzumab decreases arr independent previous therapy including patients disease activity natalizumab overall 90 patients showed disease progression 20 improvement two years alemtuzumabpmid34558755 doi101111 ene15121,0.0
identification modified dynamic gait index cutoff scores assessing fall risk people parkinson disease stroke multiple sclerosis gait posture 2021 oct 2 9116 doi 101016 jgaitpost202109201 online ahead printabstractbackground balance gait impairments increase fall rate injury people neurological disorders pwnd modified dynamic gait index mdgi scale assessing dynamic balance walking however ability identifying fallers recurrent fallers studiedresearch question evaluate mdgis ability identifying retrospective fallers recurrent fallers establishing cutoff scores use clinical practicemethod crosssectional study number retrospective falls mdgi scores collected pwnd categorised nonfallers fallers falls1 recurrent fallers falls2 nonrecurrent nonfallers falls2 according number retrospective falls two months two generalised linear logistic models developed using machine learning method detect fallers model 1 recurrent fallers model 2 based mdgi scores roc curves used identify mdgi cutoff scores distinguish different fall categoriesresults 58 pwnd mean standard deviation age 634 12 years including 28 people multiple sclerosis 15 people parkinsons disease 15 people stroke analysed mdgi score median iqr nonfallers fallers recurrent fallers nonrecurrent nonfallers respectively 50 22 37 22 265 2025 465 205 points cutoff identify fallers nonfallers 49 points sensitivity100 specificity50 posttest probability mdgi cutoff 532 posttest probability mdgi cutoff 0 auc068 29 points sensitivity60 specificity79 posttest probability mdgi cutoff521 posttest probability mdgi cutoff161 auc070 best cutoff identify recurrent fallerssignificance people mdgi score49 points low minimal fall risk people mdgi score49 points investigated scales starting balancefocused rehabilitation intervention people scoring 29 points mdgi scale may need fall prevention intervention regardless results balance clinical measurespmid34628216 doi101016 jgaitpost202109201,0.0
lesion features mri discriminate multiple sclerosis patients eur j neurol 2021 aug 17 doi 101111 ene15067 online ahead printabstractbackground mri provides insight various pathological processes multiple sclerosis ms may provide insight patterns damage among patientsobjective sought determine mri features clinical discriminative power among cohort ms patientsmethods ninetysix relapsing remitting seven progressive ms patients underwent myelin water fraction mwf imaging conventional mri cortical thickness thalamic volume patients clustered based lesion level mri features using agglomerative hierarchical clustering algorithm based principal component analysis pca results 103 patients 1689 ms lesions analyzed pca mri features demonstrated lesion mwf volume distributions characterized 25th 50th 75th percentiles accounted 87 total variability based four principal components best hierarchical cluster confirmed two distinct patient clusters clustering features order importance lesion median mwf mwf 25th mwf 75th volume 75th percentiles median individual lesion volume total lesion volume cortical thickness thalamic volume pvalues 001368 clusters associated patient edss n103 p00338 baseline five years n72 p00337 conclusion results demonstrate individual mri features can identify two patient clusters driven lesionbased values unique approach analysis blinded clinical variables two distinct clusters exhibit mwf differences likely representing individual remyelination capabilities among different patient groups findings support concept patientspecific pathophysiological processes may guide future therapeutic approachespmid34402140 doi101111 ene15067,1.0
foundations lesion detection using machine learning clinical neuroimaging acta neurochir suppl 2022 134171182 doi 101007 9783030852924_21abstractthis chapter describes technical considerations current future clinical applications lesion detection using machine learning clinical setting lesion detection central neuroradiology precedes processes include limited lesion characterization quantification longitudinal disease assessment prognosis prediction treatment response number machine learning algorithms focusing lesion detection developed currently development may either support extend imaging process examples include machine learning applications stroke aneurysms multiple sclerosis neurooncology neurodegeneration epilepsypmid34862541 doi101007 9783030852924_21,0.0
compass guide insights th17 cellular metabolism autoimmunity immunometabolism 2022 4 1 e220001 doi 1020900 immunometab20220001 epub 2021 nov 18abstractt cells rapidly convert cellular metabolic requirements upon activation switching highly glycolytic program satisfy increasingly complex energy needs fundamental metabolic differences established development foxp3+ t regulatory treg cells versus th17 cells alterations can drive disease th17 cell dysregulation driver autoimmunity chronic inflammation contributing pathogenesis diseases multiple sclerosis recent paper published cell wagner et al combined scrnaseq metabolic mapping data interrogate potential metabolic modulators th17 cell pathogenicity compass th17 cell metabolism highlights polyamine pathway critical regulator th17 treg cell function signifying potential therapeutic targetpmid34900348 pmcpmc8654074 doi1020900 immunometab20220001,0.0
unraveling mribased microstructural signatures behind primary progressive relapsingremitting multiple sclerosis phenotypes j magn reson imaging 2021 jun 30 doi 101002 jmri27806 online ahead printabstractbackground mechanisms driving primary progressive relapsingremitting multiple sclerosis ppms rrms phenotypes unknown magnetic resonance imaging mri studies support involvement gray matter gm degeneration highlighting damage early feature phenotypes however role gm microstructure unclear calling new methods decryptionpurpose investigate morphometric microstructural gm differences ppms rrms characterize gm tissue degeneration using mristudy type prospective crosssectional studysubjects fortyfive ppms 26 females 45 rrms 32 females patientsfield strength sequence 3t scanner threedimensional 3d fast field echo t1weighted t1w 3d turbo spin echo tse t2w 3d tse fluidattenuated inversion recovery spin echoecho planar imaging diffusion mri dmri assessment t1w dmri data employed providing information morphometric microstructural features respectively dmri diffusion tensor imaging 3d simple harmonics oscillator based reconstruction estimation models used feature extraction predefined set regions support vector machine svm used perform patients classification relying measuresstatistical tests differences ms phenotypes investigated using analysis covariance statistical tests p 005 considered statistically significant results dmri indices showed significant microstructural alterations considered ms phenotypes example mode median return plane probability hippocampus conversely thalamic volume morphometric feature significantly different two ms groups ten 12 features retained selection process discriminative across two ms groups regarded hippocampus svm classifier using selected features reached accuracy 70 precision 69data conclusion provided evidence support ability dmri discriminate ppms rrms well highlight central role hippocampuslevel evidence 2 technical efficacy stage 3pmid34189804 doi101002 jmri27806,0.0
sex differences neurodegeneration role immune system humans biol psychiatry 2021 jan 8s00063223 21 000391 doi 101016 jbiopsych202101002 online ahead printabstractgrowing evidence supports significant involvement immune dysfunction etiology neurodegenerative diseases several also display prominent sex differences across prevalence pathology symptomology review summarize evidence human studies established recent findings sex differences multiple sclerosis alzheimers disease parkinsons disease amyotrophic lateral sclerosis discuss sexspecific central nervous system innate immune activity contribute downstream sex differences diseases examine human genomic transcriptomics studies neurodegenerative disease lens sex differences neuroimmune system highlight importance stratifying sex clinical translational research studies finally discuss limitations existing studies outline recommendations advancing sexbased analyses uncover novel disease mechanisms ultimately help treat sexespmid33715827 doi101016 jbiopsych202101002,0.0
tumor syndromes neurosurgical evaluation management neurosurg clin n 2022 jan 33 1 91104 doi 101016 jnec202109007 epub 2021 oct 26abstractthere multiple syndromes associated tumors central nervous system cns common cns tumor syndrome neurofibromatosis1 welldefined major minor criteria needed diagnosis syndromes variable degree cns extracns involvement neurosurgeon aware include neurofibromatosis2 turcot syndrome cowden syndrome gorlin syndrome lifraumeni syndrome ataxiatelangiectasia multiple endocrine neoplasia type 1 von hippellindau syndrome tuberous sclerosis complex although cns tumor syndromes follow autosomal dominant pattern inheritance genetic underpinnings disease complex increasingly better understoodpmid34801146 doi101016 jnec202109007,0.0
blood trace element status multiple sclerosis systematic review metaanalysis biol trace elem res 2021 feb 21 doi 101007 s12011021026215 online ahead printabstractthe aim metaanalysis investigate whether blood concentrations patients multiple sclerosis ms associated healthy control group terms trace elements including zinc zn iron fe manganese mn magnesium mg selenium se copper cu comprehensive search performed online databases including pubmed scopus embase web science studies addressed trace elements ms july 23 2020 chisquare test i2 statistic utilized evaluate interstudy heterogeneity across included studies weighted mean differences wmds corresponding 95 ci considered pooled effect size es twentyseven articles 32 studies total sample comprised 2895 participants ms patients n 1567 controls n 1328 included pooled results using randomeffects model indicated levels zn wmd 783 mcg dl 95 ci 1278 287 z 309 p 0002 fe wmd 1366 mcg dl 95 ci 2313 419 z 283 p 0005 significantly lower ms patients controls however found levels mn wmd 003 mcg dl 95 ci 001 004 z 289 p 0004 significantly higher ms patients yet significant differences observed levels mg se cu groups metaanalysis revealed circulating levels zn fe significantly lower ms patients mn level significantly higher control group however found significant difference ms patients controls regard levels mg se cupmid33611740 doi101007 s12011021026215,0.0
longitudinal sodium mri multiple sclerosis lesions added value sodium inversion recovery mri j magn reson imaging 2021 jul 14 doi 101002 jmri27832 online ahead printabstractbackground sodium enhancement demonstrated multiple sclerosis ms lesionspurpose investigate sodium mri without inversion recovery pulse acute ms lesions ms relapse recoverystudy type prospectivesubjects twentynine relapsingremitting ms patients acute relapse includedfield strength sequence 3d densityadapted radial sodium sequence 3 t using dualtuned 23 na 1 h head coilassessment fullbrain images tissue sodium concentration tsc1 n 29 sodium inversion recovery sequence sir1 n 20 beginning antiinflammatory therapy mediumterm followup visits days 2799 n 12 tsc n 5 sir measured regions interest rois contrast enhancement t1 ce+ without change t1weighted imaging fl + t1n normalized ntsc nsir gain insight origin tsc enhancement time point 1 investigated whether ntsc enhancement lesions accompanied change respective nsir potential prognostic value nsir1 examined referring ntsc progression statistical tests ntsc nsir compared regarding type lesion time point using oneway anova pearsons correlation coefficient calculated ntsc nsir ntsc1ntsc2 nsir1 pvalue 005 considered statistically significantresults first measurement lesion types showed increased ntsc nsir decreased fl + t1 n t1 ce+ lesions comparison normalappearing white matter acute lesions difference ntsc baseline ntsc time point 2 showed significant correlation baseline nsirdata conclusion time point 1 ntsc increased nsir unchanged decreased lesions mean sodium ir signal baseline correlates recovery progression acute lesionevidence level 2 technical efficacy stage 4pmid34259373 doi101002 jmri27832,0.0
impact comorbidities disability progression multiple sclerosis acta neurol scand 2021 aug 20 doi 101111 ane13516 online ahead printabstractobjectives investigation comorbidity burden persons multiple sclerosis pwms become increasingly important aim study investigate relationships cardiovascular disease cvd comorbidities type 2 diabetes disability progressionmaterials methods retrospective cohort study conducted clinic neurology belgrade belgrade ms population registry comprises 2725 active ms cases used source data mean duration disease 216 125 years expanded disability status scale edss followed pwms registry statistical analysis cox proportional hazard regression analysis kaplanmeier curve performedresults hypertension statistically significantly contributed rapid reaching investigated levels irreversible disability edss 40 60 70 presence investigated cvd comorbidities type 2 diabetes significantly contributed faster reaching edss 40 edss 60 multivariable model progression index pi singled hr 3171 p 001 indicating higher progression index pi independent predictor cvd occurrence ms patients case type 2 diabetes pi p 001 ms phenotype p 015 statistically significant multivariable cox regression analysisconclusions study confirms impact cvd comorbidities type 2 diabetes ms progression disability measured edss large cohort pwms population registrypmid34414566 doi101111 ane13516,0.0
childhood maltreatment psychiatric comorbidity immunemediated inflammatory disorders psychosom med 2021 oct 12 doi 101097 psy0000000000001025 online ahead printabstractobjective determine whether childhood maltreatment associated immunemediated inflammatory disorders imid multiple sclerosis ms inflammatory bowel disease ibd rheumatoid arthritis ra aimed determine relationship maltreatment psychiatric comorbidity imid whether relationships differed across imidmethods 681 participants ms 232 ibd 216 ra 130 healthy controls 103 completed structured psychiatric interview identify psychiatric disorders childhood trauma questionnaire evaluate five types maltreatment emotional abuse physical abuse sexual abuse emotional neglect physical neglect evaluated associations maltreatment imid psychiatric comorbidity using multivariable logistic regression modelsresults prevalence 1 maltreatment similar across imid higher controls ms 638 ibd 616 ra 623 healthy controls 456 emotional abuse associated imid adjusted odds ratio aor 237 115489 sexspecific analysis association present women history childhood maltreatment associated lifetime diagnosis psychiatric disorder imid cohort 224 158316 association differ across diseases imid total types maltreatments aor 136 117159 emotional abuse aor 264 166421 associated psychiatric comorbidityconclusions childhood maltreatment common imid healthy population associated psychiatric comorbidity given high burden psychiatric disorders imid population clinicians aware contribution maltreatment potential need traumainformed care strategiespmid34654023 doi101097 psy0000000000001025,0.0
ultrahighb diffusionweighted imaging quantitative evaluation myelination shiverer mouse spinal cord magn reson med 2021 aug 21 doi 101002 mrm28978 online ahead printabstractpurpose perform quantitative evaluation myelination wt myelindeficient shiverer mouse spinal cords using ultrahighb diffusionweighted imaging uhbdwi methods uhbdwi ex vivo spinal cord specimens two shiverer c3heb fejshiverer homozygous genotype mbpshi six wt black six c3heb fej mice acquired using 3d multishot diffusionweighted stimulatedecho epi homemade rf coil smallbore 7t mri system imaging performed transaxial plane 75 75 m2 inplane resolution 1mmslice thickness radial dwi using bmax 42 890 s mm2 histological evaluation performed upper thoracic sections using optical transmission electron microscopy numerical monte carlo simulations mcss water diffusion performed facilitate interpretation uhbdwi signalb curvesresults white matter ultrahighb radial dwi uhbrdwi signalb curves wt mouse cords behaved biexponentially highb diffusion coefficient dh 0020 103 mm2 s however expected less myelination signalb shiverer mouse cords behaved monoexponentially significantly greater dh 0162 103 0142 103 0164 103 mm2 s anterodorsal posterodorsal lateral columns respectively axial dwi signals mouse cords behaved monoexponentially d 07181124 103 mm2 s mcs suggests elevated dh mainly induced increased water exchange myelin sheath microscopic results consistent uhbrdwi findingsconclusion uhbdwi provides quantitative differences myelination spinal cords myelindeficit shiverer wt mice uhbdwi may become powerful tool evaluate myelination demyelinating disease models may translate human diseases including multiple sclerosispmid34418157 doi101002 mrm28978,1.0
multiple sclerosis 2021 progress progression papers multiple sclerosis published 2021 portray field transition previous focus blocking acute inflammation gradually yielding investigations origins disease prevention biological basis disability progression amelioration,1.0
anticd20 therapies decrease humoral immune response sarscov2 patients multiple sclerosis neuromyelitis optica spectrum disorders j neurol neurosurg psychiatry 2021 aug 2jnnp2021326904 doi 101136 jnnp2021326904 online ahead printabstractbackground sarscov2 seroconversion rate covid19 may influenced diseasemodifying therapies dmts patients multiple sclerosis ms neuromyelitis optica spectrum disorders nmosd objective investigate seroprevalence quantity sarscov2 antibodies cohort patients ms nmosdmethods blood samples collected patients diagnosed covid19 19 february 2020 26 february 2021 sarscov2 antibody positivity rates ig levels antis igg titre antis iga index antin igg index compared dmts groups multivariate logistic linear regression models used estimate influence dmts confounding variables sarscov2 serological outcomesresults 119 patients 115 ms 4 nmo mean age 430 years analysed overall seroconversion rate 806 within 50 sd 34 months infection 20 21 952 patients without dmt 66 77 857 patients dmts anticd20 least one sarscov2 ig positivity rate decreased 10 21 476 patients anticd20 p0001 anticd20 associated decreased odd positive serology 007 95 ci 001 069 p002 independently time covid19 total igg level age sex covid19 severity time last anticd20 infusion covid19 longer mean sd 37 20 months seropositive patients compared seronegative patients mean sd 19 15 months p004 conclusions sarscov2 antibody response decreased patients ms nmosd treated anticd20 therapies monitoring longterm risk reinfection specific vaccination strategies population may warrantedtrial registration number nct04568707pmid34341142 doi101136 jnnp2021326904,0.0
pathological phase transitions alsftd impair dynamic rnaprotein granules rna 2021 oct 27rna079001121 doi 101261 rna079001121 online ahead printabstractthe genetics human disease serves robust unbiased source insight human biology revealing fundamental cellular processes exposing vulnerabilities associated dysfunction last decade genetics amyotrophic lateral sclerosis als frontotemporal dementia ftd epitomized concept studies alsftdcausing mutations yielded fundamental discoveries regarding role biomolecular condensation organizing cellular contents implicating disturbances condensate dynamics central drivers neurodegeneration review genetic evidence highlight intersection patient pathology discuss studies model systems revealed role aberrant condensation neuronal dysfunction death detail multiple distinct types diseasecausing mutations promote pathological phase transitions disturb dynamics function ribonucleoprotein rnp granules dysfunction rnp granules causes pleiotropic defects rna metabolism can drive evolution structures endstage pathological inclusions characteristic alsftd propose aberrant phase transitions complex condensates cells provide parsimonious explanation widespread cellular abnormalities observed als well certain histopathological features characterize latestage diseasepmid34706979 doi101261 rna079001121,0.0
comprehensive review il26 pave new way profound understanding pathobiology cancer inflammatory diseases infections immunology 2021 oct 30 doi 101111 imm13424 online ahead printabstractcytokines considered vital mediators immune system upregulation mediators linked several inflammatory pathologic situations il26 referred identified member il10 family il20 subfamily due unique cationic structure il26 exerts diverse functions several diseases since il26 mainly secreted th17 primarily considered proinflammatory cytokine upon binding receptor complex il10r1 il20r2 il26 activates multiple signaling mediators especially stat1 stat3 cancer il26 induces il22producing cells consequently decreases cytotoxic t cell functions promotes tumor growth activating antiapoptotic proteins hypersensitivity conditions rheumatoid arthritis multiple sclerosis psoriasis allergic disease cytokine functions primarily diseasepromoting mediator might considered biomarker disease prognosis although il26 exerts antimicrobial function infections hepatitis tuberculosis leprosy also shown il26 might involved pathogenesis exacerbation sepsis besides involvement il26 confirmed conditions including graft versus host disease chronic obstructive pulmonary disease therefore due multifarious function cytokine proposed underlying mechanism regarding il26 function elucidated collectively hoped examination il26 several contexts might promising predicting disease prognosis might introduce novel approaches treatment various diseasespmid34716913 doi101111 imm13424,0.0
silent progression brain atrophy aquaporin4 antibodypositive neuromyelitis optica spectrum disorder j neurol neurosurg psychiatry 2021 aug 6jnnp2021326386 doi 101136 jnnp2021326386 online ahead printabstractobjective investigate longitudinal brain atrophy patients neuromyelitis optica spectrum disorder nmosd methods investigated longitudinal brain atrophy rate patients aquaporin4 antibodypositive nmosd aqp4+nmosd multiple sclerosis ms retrospective cohort study brain volume calculated statistical parametric mapping12results enrolled 36 patients aqp4+nmosd 60 ms patients nmosd older higher kurtzkes expanded disability status scale score baseline mri compared ms disease duration annual relapse rate intervals last attack diseasemodifying drugs initiation significantly different two groups lower normalised lesion volume higher normalised white matter volume found patients nmosd compared ms baseline mri however annualised atrophy rate normalised brain volume similar nmosd median 047 iqr 075 p049 ms median 046 iqr 084 groups adjustment age presence clinical relapse differences annualised atrophy rate normalised brain volume also found nmosd ms patients aqp4+nmosd long cord lesion showed higher annualised atrophy rate normalised grey matter volume compared without long cord lesionconclusions silent progression brain atrophy present patients aqp4+nmosd shown patients ms even clinically inactive agematched cases subclinical dying back degeneration may explain brain atrophy patients aqp4 +nmosdpmid34362853 doi101136 jnnp2021326386,0.0
exosomes derived bone marrow mesenchymal stromal cells promote remyelination reduce neuroinflammation demyelinating central nervous system exp neurol 2021 oct 12113895 doi 101016 jexpneurol2021113895 online ahead printabstractinjury oligodendrocytes ols induces demyelination patients neurodegenerative diseases exhibit demyelination concomitantly neurological deficit cognitive impairment oligodendrocyte progenitor cells opcs present adult central nervous system cns can proliferate differentiate remyelinate axons damage however remyelination therapies clinical use multiple sclerosis ms major demyelinating disease cns mesenchymal stromal cells mscs demonstrated therapeutic promise animal models clinical trials ms exosomes nanoparticles generated nearly cells mediate cellcell communication transferring cargo biomaterials hypothesize exosomes harvested mscs similar therapeutic effect enhancement remyelination mscs present study employed exosomes derived rhesus monkey mscs mscexo two mouse models demyelination employed 1 experimental autoimmune encephalomyelitis eae animal model ms 2 cuprizone cpz diet model toxic demyelination model mscexo pbs intravenously injected twice week 4 weeks starting day 10 post immunization eae mice week 2 weeks starting day cpz diet withdrawal neurological cognitive function tested opc differentiation remyelination neuroinflammation potential underlying mechanisms investigated using immunofluorescent staining transmission electron microscopy western blot data generated eae model revealed mscexo cross blood brain barrier bbb target neural cells compared controls p 005 treatment mscexo 1 significantly improved neurological outcome 2 significantly increased numbers newly generated ols brdu+ apc+ mature ols apc+ level myelin basic protein mbp 3 decreased amyloid precursor protein app + density 4 decreased neuroinflammation increasing m2 phenotype decreasing m1 phenotype microglia well related cytokines 5 inhibited tlr2 irak1 nfb pathway furthermore confirmed mscexo treatment significantly improved cognitive function promoted remyelination increased polarization m2 phenotype blocked tlr2 signaling cpz model collectively mscexo treatment promotes remyelination directly acting opcs indirectly acting microglia demyelinating cns study provides cellular molecular basis cellfree exosome therapy remyelination modulation neuroinflammation cns great potential treatment demyelinating neurodegenerative disorderspmid34653510 doi101016 jexpneurol2021113895,1.0
therapeutic acute intermittent hypoxia translational roadmap spinal cord injury neuromuscular disease exp neurol 2021 oct 9113891 doi 101016 jexpneurol2021113891 online ahead printabstractwe review progress towards greater mechanistic understanding clinical translation strategy improve respiratory nonrespiratory motor function people neuromuscular disorders therapeutic acute intermittent hypoxia taih 2016 2020 workshops create update road map clinical translation held help guide future research development taih restore movement people living chronic incomplete spinal cord injuries briefly discussing pioneering nontargeted basic research inspiring novel therapeutic approach summarize workshop recommendations emphasizing critical knowledge gaps priorities future research effort steps needed accelerate progress evaluate potential taih routine clinical use highlighted areas include 1 greater mechanistic understanding particularly nonrespiratory motor systems 2 optimization taih protocols maximize benefits 3 identification combinatorial treatments amplify plasticity remove plasticity constraints including taskspecific training 4 identification biomarkers individuals least likely benefit taih 5 assessment longterm taih safety 6 development simple safe effective device administer taih clinical home settings finally update ongoing clinical trials recent investigations taih sci clinical disorders compromise motor function including als multiple sclerosis strokepmid34637802 doi101016 jexpneurol2021113891,0.0
higher blood high density lipoprotein apolipoprotein a1 levels associated reduced risk developing amyotrophic lateral sclerosis j neurol neurosurg psychiatry 2021 sep 13jnnp2021327133 doi 101136 jnnp2021327133 online ahead printabstractbackground premorbid body mass index physical activity diabetes cardiovascular disease associated altered risk developing amyotrophic lateral sclerosis als evidence shared genetic risk als lipid metabolism large prospective longitudinal population cohort permits study range metabolic parameters risk subsequent diagnosis alsmethods risk subsequent als diagnosis enrolled prospectively uk biobank n502 409 examined relation baseline levels blood high low density lipoprotein hdl ldl total cholesterol total cholesterolhdl ratio apolipoproteins a1 b apoa1 apob triglycerides glycated haemoglobin a1c hba1c creatinine plus selfreported exercise body mass indexresults controlling age sex higher hdl hr 084 95 ci 073 096 p0010 apoa1 hr 083 95 ci 072 094 p0005 associated reduced risk als higher total cholesterolhdl associated increased risk als hr 117 95 ci 105 131 p0006 models incorporating multiple metabolic markers higher ldl apob associated increased risk als addition lower risk higher hdl apoa coronary artery disease cerebrovascular disease increasing age also associated increased risk alsconclusions association hdl apoa1 ldl levels risk als contributes increasing body evidence premorbid metabolic landscape may play role pathogenesis understanding molecular basis changes will inform presymptomatic biomarker development therapeutic targetingpmid34518331 doi101136 jnnp2021327133,0.0
drug connectivity mapping functional analysis reveal therapeutic small molecules differentially modulate myelination biomed pharmacother 2021 nov 20 145112436 doi 101016 jbiopha2021112436 online ahead printabstractdisruption loss oligodendrocytes ols myelin devastating effects cns function integrity occur diverse neurological disorders including multiple sclerosis ms alzheimers disease neuropsychiatric disorders hence need develop new therapies promote oligodendrocyte regeneration myelin repair promising approach drug repurposing agents potentially contrasting biological actions depending cellular context dosedependent effects intracellular pathways used combined systems biology neurobiological approach identify compounds exert positive negative effects oligodendroglia depending concentration notably next generation pharmacogenomic analysis identified pi3k akt modulator ly294002 highly ranked small molecule pro antioligodendroglial concentrationdependent effects validated silico findings using multidisciplinary approaches reveal profoundly bipartite effect ly294002 generation opcs differentiation myelinating oligodendrocytes postnatal adult contexts finally employed transcriptional profiling signalling pathway activity assays determine cellspecific mechanisms action ly294002 oligodendrocytes resolve optimal vivo conditions required promote myelin repair results demonstrate power multidisciplinary strategies determining therapeutic potential small molecules neurodegenerative disorderspmid34813998 doi101016 jbiopha2021112436,1.0
higher quality diet nonconsumption meat associated less selfdetermined disability progression people multiple sclerosis longitudinal cohort study eur j neurol 2021 aug 14 doi 101111 ene15066 online ahead printabstractbackground modifiable lifestyle factors including diet affect clinical outcomes multiple sclerosis ms study assessed relationships diet disability fatigue depressionrisk people msmethods participants holism international cohort assessed 25years dietary data obtained using modified diet habits questionnaire dhq disability calculated patientdetermined ms severity score pmsss fatigue using fatigue severity scale depressionrisk patient health questionnaire2 participants reported whether experiencing symptoms due recent relapse crosssectional prospective relationships diet disease outcomes explored adjusted relevant confoundersresults among 1 346 participants higher dhq scores showed significant dosedependent associations lower frequencies severe disability fatigue depressionrisk crosssectionally prospectively higher baseline dhq scores associated lower risk increasing disability median 41 36 lower risk increasing disability 030 pmsss points less disability progression associated fatigue depressionrisk meat consumption associated 022 pmsss points higher disability crosssectionally prospectively baseline meat consumption associated 76 higher risk increasing disability 018 pmsss points higher disability progression dairy consumption showed mixed associations crosssectionally prospectivelyconclusions results show better quality diet well consuming meat associated reduced disability progression people ms substantiation findings settings may inform opportunities manage disability progression people ms using dietary modificationspmid34390078 doi101111 ene15066,0.0
frequency characteristics multiple sclerosis misdiagnosis latin america referral center study buenos aires argentina abstractobjectivemost contemporary data concerning frequency causes multiple sclerosis ms misdiagnosis north america europe different healthcare system structure resources countries latin america sought determine frequency potential contributors ms misdiagnosis patients evaluated ms referral center argentinamethodsthe study retrospective medical record review included patients evaluated ms clinic fleni april 2013 march 2021 diagnoses prior consultation final diagnoses consultation demographic clinical paraclinical data treatment extracted classifiedresultsseven hundred thirtysix patients identified five hundred seventytwo presented established diagnosis ms evaluation misdiagnosis identified 89 16 women 83 greater risk misdiagnosis p0034 frequent alternative diagnoses cerebrovascular disease radiological isolated syndrome ris headache seventyfour 83 misdiagnosed patients presented syndrome atypical demyelination 62 70 atypical brain magnetic resonance imaging mri 54 61 prescribed diseasemodifying therapyconclusionsixteenpercent patients established ms subsequently found misdiagnosed women higher risk misdiagnosis expert application mcdonald criteria may prevent misdiagnosis associated morbidity healthcare system cost,1.0
treatment cladribine selects ifn+il17+ t cells rrms patients vitro study front immunol 2021 dec 14 12743010 doi 103389 fimmu2021743010 ecollection 2021abstractbackground multiple sclerosis ms incurable autoimmune disease mediated heterogeneous t cell population cd3+cd161+cxcr3ccr6+ifnil17+ cd3+cxcr3+ccr6+ifn+il17+ cd3+cxcr3+ifn+il17 phenotypes infiltrates central nervous system eliciting local inflammation demyelination neurodegeneration cladribine lymphocytedepleting deoxyadenosine analogue recently introduced ms therapy disease modifying drug dmd aim establish method early identification prediction cladribine responsiveness among ms patientsmethods experimental model designed study cytotoxic immunomodulatory effect cladribine t cell subsets nave relapsingremitting ms rrms patients analyzed ex vivo vitro comparatively healthy controls hc surviving cells stimulated rhinterleukin2 14days cell proliferation immunophenotype changes analyzed maximal phorbol myristate acetate ionomycin monensin physiological tcell receptor cd3 cd28 activation using multiparametric flow cytometry xmap technologyresults ex vivo cd161+th17 cells increased rrms patients ex vivo vitro phenotype shifts included decreased cd3+ccr6+ cd3+cd161+ subjects increased cd3+cxcr3+ rrms patients th171 showed increased proliferation vs th17 subjects cd3+il17+ cd3+ifn+il17+ continued proliferate till day 14 cd3+ifn+ till day 7 regarding cladribine exposure rrms cd3+ cells resistant compared hc treated cd3+ cells proliferated continuously 14 days untreated cells 7 days hc rrms cd3+cxcr3+ populations increased baseline till day 14 rrms patients vs hc il17 secretion cladribinetreated cells increased significantly line observed proliferation cd3+il17+ cd3+ifn+il17+ cells hc rrms cladribine led significant increase cd3+ifn+ cells day 7 effect day14 ifn il17 secreted culture media decreased significantly ex vivo vitroconclusions cd3+ subtypes showed different responsiveness due selectivity cladribine action patients leading vitro survival proliferation lymphocyte subsets known pathogenic ms vitro experimental model promising tool prediction individual responsiveness ms patients cladribine dmdspmid34970256 pmcpmc8712887 doi103389 fimmu2021743010,1.0
computational refinement identifies functional destructive single nucleotide polymorphisms associated human retinoid x receptor gene j biomol struct dyn 2021 dec 31121 doi 101080 0739110220212021991 online ahead printabstractalterations nuclear retinoid x receptor rxrs signalling implicated neurodegenerative disorders alzheimers disease parkinsons disease stroke multiple sclerosis glaucoma single nucleotide polymorphisms snps main cause underlying single nucleic acid variations turn determine heterogeneity within various populations genetic polymorphisms suggested associate various degenerative disorders populationwide analysis bioinformatics study designed investigate search retrieve identify deleterious snps may affect structure function various rxr isoforms computational molecular modelling approach amongst 1 813 retrieved snps several found deleterious rs140464195_g139r rs368400425_r358w rs368586400_l383f rxr mutant variants detrimental ones causing changes interatomic interactions decreasing flexibility mutant proteins molecular genetics analysis identified seven missense mutations rxr isoforms two novel mutations snp ids rs1588299621 rs1057519958 identified rxr isoform used several silico prediction tools sift polyphen imutant protein variation effect analyzer provean panther snpgo phdsnp snpeffect predict pathogenicity protein stability associated rxr mutations structural assessment dynamut tool revealed hydrogen bonds affected along hydrophobic carbonyl interactions resulting reduced flexibility mutated residue positions ultimately stabilizing molecule whole summarizing analysis missense mutations rxr isoforms showed mix conclusive inconclusive genotypephenotype correlations suggesting use sophisticated computational analysis tools studying rxr variantscommunicated ramaswamy h sarmapmid34971346 doi101080 0739110220212021991,0.0
comparison nephroscopy cystoscopy used treatment bladder stones systematic review metaanalysis randomized controlled trials background systematic review metaanalysis conducted compare safety efficiency nephroscopy cystoscopy transurethral cystolithotripsy tucl bladder stones bs methodsthe pubmed web science embase ebsco cochrane library databases searched january 2021 studies assessing effect different types endoscopes among patients underwent tucl search strategy study selection process accordance prisma statementresults five randomized controlled trials included metaanalysis results showed difference stonefree rate rr 100 ci 098102 p 100 two groups nonsignificant heterogeneity i2 0 p 100 patients rendered stone free use nephroscope significantly shortened operative time compared cystoscope group rr 2626 ci 3584 1668 p 000001 significant heterogeneity i2 87 p 000001 significant difference mean urethral entries rr 066 ci 071 204 p 035 hospitalization md 008 95 ci 007 023 p 031 total complication rate rr137 95 ci 047400 p 056 two groupsconclusionsin conclusion systematic review demonstrates nephroscopy cystoscopy high stone clearance efficiency low rates complications short hospitalizations mean urethral entries depend treatment method large stone fragments however use nephroscopy can significantly reduce operative time,0.0
absence attackindependent neuroaxonal injury mog antibodyassociated disease longitudinal assessment serum neurofilament light chain abstractto evaluate occurrence attackindependent neuroaxonal astrocytic damage myelin oligodendrocyte glycoprotein antibodyassociated disease mogad serum neurofilament light chain snfl serum glial fibrillary acidic protein sgfap levels longitudinally measured 102 sera using singlemolecule array assay sera 15 adults relapsing mogad available longitudinal samples median 24month followup 26 age sexmatched healthy controls analyzed snfl levels significantly elevated clinical attacks levels decreased close cutoff value within 6 months attacks snfl levels consistently low interattack periods contrast sgfap levels increase clinical attacks remained low followup significant neuroaxonal damage observed clinical attacks attackindependent neuroaxonal astrocytic injury absent mogad,1.0
cognitive dysfunction mortality multiple sclerosis longterm retrospective review abstractbackgroundcognitive dysfunction predictor clinical progression mortality multiple sclerosis ms still matter debateobjectivethe aim study explore longterm outcome associated neuropsychological performance cohort patients msmethodsa series 408 ms patients previously undergone comprehensive neuropsychological assessment contemporaneous neurological evaluation t1 retrospective review clinical records conducted 102192months t1 demographic clinical data regarding last clinical appointment edss measurement t2 collected date last clinical contact death ts recordedresultsthis review revealed cognitive dysfunction t1 associated higher odds transitioning relapsingremitting course progressive disease course adjusted odds ratio 229 p0043 higher hazard death total sample adjusted hazard ratio hr 307 p0006 progressive disease course subgroup adjusted hr368 p0007 even adjusting covariatesdiscussionthe study results demonstrate cognitive dysfunction ms predictive poorer prognosis mortality,0.0
impact clinical outcomes imaging measures healthrelated quality life secondary progressive ms abstractbackgroundhealthrelated quality life hrqol outcomes often included secondary outcomes clinical trials secondary progressive ms spms little known longitudinal association hrqol clinical imaging outcome measures spmsobjectiveto assess association change clinical imaging outcomes hrqol people spmsmethodswe used data ascend large randomized controlled trial n889 investigate association significant worsening expanded disability status scale edss timed 25 foot walk t25fw nine hole peg test nhpt symbol digit modalities test sdmt change lesional volumetric imaging outcomes significant worsening 36item short form health survey sf36 multiple sclerosis impact scale msis29 2 years followup using logistic regression modelsresultshrqol measures associated edss t25fw less nhpt sdmt associated lesional volumetric imaging outcomesdiscussionworsening edss t25fw associated two commonly used hrqol measures outcomes therefore appear patient relevant either nhpt sdmt context 2year clinical trial,0.0
contribute cerebrospinal fluid free lightchain assay diagnosis multiple sclerosis neurological diseases italian multicenter study abstractbackgroundcerebrospinal fluid csf free light chains flcs can alternative assay oligoclonal bands ocbs inflammatory neurological disorders threshold consensusobjectiveto assess diagnostic accuracy csf flcs multiple sclerosis ms neurological diseasesmethodsa total 406 patients five italian centers flcs measured csf serum using freelite mx assays optiliteresultsa total 171 patients diagnosed ms 154 noninflammatory neurological diseases 48 inflammatory central nervous system cns diseases 33 peripheral neurological diseases kflc flc indices significantly higher patients ms compared groups p00001 kflc index64 comparable ocb ms diagnosis area receiver operating characteristic curve auc 0876 sensitivity 836 vs 842 specificity 885 vs 906 flc index5 showed auc 0616 sensitivity 333 specificity 906 12 27 444 ms patients negative ocb kflc index64 interestingly 375 24 patients single csf igg band showed high kflc index 125 positive flc indexconclusionour findings support diagnostic utility flc indices ms cns inflammatory disorders suggesting combined use flc ocb help clinicians complementary information,0.0
assessing cognitive function multiple sclerosis digital tools observational study j med internet res 2021 dec 30 23 12 e25748 doi 102196 25748abstractbackground cognitive impairment ci one prevalent symptoms multiple sclerosis ms however difficult include cognitive assessment part ms standard care since comprehensive neuropsychological examinations usually timeconsuming extensiveobjective improve access ci assessment evaluated feasibility potential assessment sensitivity tabletbased cognitive battery patients msmethods total 53 participants ms 24 45 ci 29 55 without ci 24 nonms participants assessed tabletbased cognitive battery adaptive cognitive evaluation ace standard cognitive measures including symbol digit modalities test sdmt paced auditory serial addition test pasat associations performance ace sdmt pasat explored group comparisons evaluate whether ace modules can capture grouplevel differencesresults correlations performance ace sdmt r057 p001 well pasat r039 p01 observed compared nonms nonci ms groups ci ms group showed slower reaction time ci ms vs nonms p001 ci ms vs nonci ms p004 higher attention cost ci ms vs nonms p02 ci ms vs nonci ms p001 conclusions results provide preliminary evidence ace tabletbased cognitive assessment battery provides modules potentially serve digital cognitive assessment people mstrial registration clinicaltrialsgov nct03569618 https clinicaltrialsgov ct2 show nct03569618pmid34967751 doi102196 25748,0.0
simulated diagnostic performance lowfield mri harnessing openaccess datasets evaluate novel devices magn reson imaging 2021 dec 27s0730725x 21 002575 doi 101016 jmri202112007 online ahead printabstractthe purpose study demonstrate method virtually evaluating novel imaging devices using machine learning openaccess datasets applied new lowfield strength portable 64mt mri device paired 3 t 64mt brain images used develop validate transformation converting standard clinical images lowfield quality images separately 3 t images aggregated opensource databases spanning four neuropathologies lowgrade glioma lgg n 76 highgrade glioma hgg n 259 stroke n 28 multiple sclerosis ms n 20 transformation method applied opensource data generate simulated lowfield images pathology convolutional neural networks densenet121 trained detect pathology axial slices either 3 t simulated 64 mt images relative performance compared characterize potential diagnostic capabilities lowfield imaging algorithm performance measured using area receiver operating characteristic curve across cohorts pathology detection similar 3 t simulated 64mt images lgg 097 vs 098 hgg 096 vs 095 stroke 094 vs 094 ms 090 vs 087 pathology detection characterized function lesion size intensity contrast simulated images showed decreasing sensitivity lesions smaller 4 cm2 simulations replace prospective trials evaluation medical devices can provide guidance justification prospective studies simulated data derived opensource imaging databases may facilitate testing validation new imaging devicespmid34968700 doi101016 jmri202112007,0.0
subcortical volumes early predictors fatigue multiple sclerosis ann neurol 2021 dec 30 doi 101002 ana26290 online ahead printabstractobjective fatigue frequent severe symptom multiple sclerosis ms pathophysiological origin remains incompletely understood aimed examine predictive value subcortical gray matter volumes fatigue severity disease onset four years applying structural equation modeling sem methods multicenter cohort study included 601 treatmentnaive ms patients first demyelinating event patients underwent standardized 3t mri protocol subgroup 230 patients available clinical followup data four years also analyzed associations subcortical volumes included sem msrelated fatigue studied regarding predictive value addition subcortical regions central role brain network hubs determined structural covariance network scn analysisresults predictive causal modeling identified volumes caudate s standardized path coefficient 0763 p0003 left s0755 p0006 right putamen s0614 p0002 left s0606 p0003 right pallidum s0606 p0012 left s0606 p0012 right prognostic factors fatigue severity crosssectional cohort moreover volume pons additionally predictive fatigue severity longitudinal cohort s0605 p0013 scn analysis network hubs patients fatigue worsening detected putamen p0008 left p0007 right pons p00001 interpretation unveiled predictive associations specific subcortical gray matter volumes fatigue early initially untreated ms cohort colocalization subcortical structures network hubs suggests early role brain regions terms fatigue evolution article protected copyright rights reservedpmid34967456 doi101002 ana26290,1.0
cancer incidence mortality years life lost years lived disability disabilityadjusted life years 29 cancer groups 2010 2019 systematic analysis global burden disease study 2019 jama oncol 2021 dec 30 doi 101001 jamaoncol20216987 online ahead printabstractimportance global burden diseases injuries risk factors study 2019 gbd 2019 provided systematic estimates incidence morbidity mortality inform local international efforts toward reducing cancer burdenobjective estimate cancer burden trends globally 204 countries territories sociodemographic index sdi quintiles 2010 2019evidence review gbd 2019 estimation methods used describe cancer incidence mortality years lived disability years life lost disabilityadjusted life years dalys 2019 past decade estimates also provided quintiles sdi composite measure educational attainment income per capita total fertility rate younger 25 years estimates include 95 uncertainty intervals uis findings 2019 estimated 236 million 95 ui 222249 million new cancer cases 172 million excluding nonmelanoma skin cancer 100 million 95 ui 936106 million cancer deaths globally estimated 250 million 235264 million dalys due cancer since 2010 represented 263 95 ui 203323 increase new cases 209 95 ui 142276 increase deaths 160 95 ui 93228 increase dalys among 22 groups diseases injuries gbd 2019 study cancer second cardiovascular diseases number deaths years life lost dalys globally 2019 cancer burden differed across sdi quintiles proportion years lived disability contributed dalys increased sdi ranging 14 1118 low sdi quintile 57 4271 high sdi quintile high sdi quintile highest number new cases 2019 middle sdi quintile highest number cancer deaths dalys 2010 2019 largest percentage increase numbers cases deaths occurred low lowmiddle sdi quintilesconclusions relevance results systematic analysis suggest global burden cancer substantial growing burden differing sdi results provide comprehensive comparable estimates can potentially inform efforts toward equitable cancer control around worldpmid34967848 doi101001 jamaoncol20216987,0.0
effect lesion location visuospatial attentional bias patients multiple sclerosis neuropsychology 2021 dec 30 doi 101037 neu0000763 online ahead printabstractobjective lateralization visuospatial attention healthy people known pseudoneglect results leftward bias landmark line bisection tasks cognitive dysfunctions patients multiple sclerosis ms might affect visuospatial attentional abilities well study aimed examine association atrophy lesion location extent lateralization visuospatial attentional bias patients msmethod visuospatial attentional bias measured 35 relapsingremitting ms patients using landmark task evaluate relation spatial attentional bias gray matter atrophy voxelbased morphometry performed t1weighted magnetic resonance mr images order examine effect lesion location visuospatial attentional bias lesionsymptom mapping conducted manually segmented lesionsresults variability visuospatial attentional bias higher ms patients compared healthy controls p 04 lesion probability mapping showed lesions located along left superior longitudinal fascicle associated extent visuospatial bias p 05 correlation found gray matter atrophy attentional bias patientsconclusions results indicate lesions affecting integrity white matter pathways frontoparietal attentional network might accountable higher variability spatial attentional bias patients ms psycinfo database record c 2021 apa rights reserved pmid34968127 doi101037 neu0000763,0.0
health promotion functional abilities quality life covid19 people multiple sclerosis nurs res 2021 dec 28 doi 101097 nnr0000000000000573 online ahead printabstractbackground multiple sclerosis ms autoimmune disease many individuals ms take diseasemodifying drugs suppress immune response serious concerns expressed potential effct covid19 chronic conditionobjectives purpose research utilize recent 5 years data ongoing longitudinal study health promotion quality life qol among people longstanding ms investigate changes across time functional limitations health promotion healthrelated qolmethods participants mailed annual survey complete health promotion depressive symptoms health status social support msrelated functional limitations qol differences across time analyzed repeated measures analysis variances planned contrastsresults 2021 141 participants mean age 69 years diagnosed ms 34 years average attended college married partnered females reported adequate economic resources thirtyseven percent reported poor fair health physical activity health responsibility scores decreased significantly 20202021 compared 20172019 significant changes depressive symptoms social support functional limitations scores followed different pattern largest changes occurring 2018 2019 qol health promotion scores change significantly across timediscussion relatively small changes health indicators revealed suggest older people longstanding ms may generally able maintain health promotion functional abilities qol covid19 pandemic however nurses providers support resume physical activity regular provider contact covid19 restrictions eased patterns observed demonstrate importance examining changes across extended period rather simply looking 1 year 1 year major event covid19 findings can help nurses understand help patients chronic health conditions maximize health move forwardpmid34967826 doi101097 nnr0000000000000573,0.0
episodic foresight multiple sclerosis neuropsychology 2021 dec 30 doi 101037 neu0000785 online ahead printabstractobjective episodic foresight refers ability imagine future scenarios use imaginative capacity guide futuredirected behavior multiple sclerosis ms associated deficits generating phenomenological characteristics future events imaginative component episodic foresight study date tested whether ms also associated deficits using episodic foresight appropriately guide futuredirected behaviormethod forty people relapsingremitting ms rrms 40 demographically matched healthy participants completed validated measure met strict criteria assessing functional application episodic foresight virtualweek foresight vwforesight results overall people rrms differ significantly relative comparison participants likely spontaneously acquire items later allow problem solved also just likely subsequently use items solve problem however latter group difference large magnitude just failed attain significance higher levels depression significantly related performance use component foresight rrms group depressed rrms participants significantly impaired aspect foresight relative healthy participants nondepressed rrms participants depressed ms subgroup also differed nondepressed subgroup ability perform instrumental activities daily livingconclusions people rrms present heightened levels depressive symptomatology also appear greater risk experiencing specific problems episodic foresight psycinfo database record c 2021 apa rights reserved pmid34968126 doi101037 neu0000785,0.0
dynamic functional connectivity better predicts disability structural static functional connectivity people multiple sclerosis front neurosci 2021 dec 13 15763966 doi 103389 fnins2021763966 ecollection 2021abstractbackground advanced imaging techniques diffusion functional mri can used identify pathologyrelated changes brains structural functional connectivity sc fc networks mapping changes disability compensatory mechanisms people multiple sclerosis pwms study date performed comparison study investigate connectivity type sc static dynamic fc better distinguishes healthy controls hc pwms classifies pwms disability status aims aim compare performance sc static fc dynamic fc dfc classifying hc vs pwms b pwms disability vs disability secondary objective study identify brain regions connectome measures contribute classification tasks materials methods one hundred pwms 19 hc included expanded disability status scale edss used assess disability 67 pwms edss2 considered disability diffusion restingstate functional mri used compute sc fc matrices respectively logistic regression ridge regularization performed models included demographics clinical information either pairwise entries regional summaries one following matrices sc fc dfc performance models assessed using area receiver operating curve auc results classifying hc vs pwms regional sc model significantly outperformed others median auc 089 p 005 classifying pwms disability status regional dfc dfc metrics models significantly outperformed others median auc 065 061 p 005 regional sc dorsal attention subcortical cerebellar networks important variables hc vs pwms classification task increased regional dfc dorsal attention visual networks decreased regional dfc frontoparietal cerebellar networks certain dfc states associated group pwms evidence disability discussion damage scs hallmark ms unsurprisingly accurate connectomic measure classifying patients controls hand dynamic fc metrics important determining disability level pwms represent functional compensation response white matter pathology pwmspmid34966255 pmcpmc8710545 doi103389 fnins2021763966,0.0
minireview sarscov2 infection neurological manifestations perspective cns neurol disord drug targets 2021 jul 6 doi 102174 1871527320666210706103422 online ahead printabstractthe coronavirus also known sarscov2 severe acute respiratory syndrome corona virus19 rapid rate transmission progressed great impact respiratory function mortality worldwide nasal cavity promising gateway sarscov2 reach brain via systemic circulatory distribution recent reports revealed loss involuntary process breathing control brainstem results death signal neurological involvement early neurological symptoms like loss smell convulsions ataxia clues involvement central nervous system makes entry sarscov2 fatal lifethreatening requiring artificial respiration emergency admission hospitals studies performed patients infected sarscov2 revealed threestage involvement central nervous system cns progression sarscov2 infection direct involvement cns headache ataxia dizziness altered impaired consciousness acute stroke seizures major symptoms peripheral involvement impaired taste smell vision altered nociception skeletal muscle impairment includes skeletal muscle disorders leading acute paralysis particular area body previous era studied researched viruses beta coronavirus mouse hepatitis virus studied acute chronic encephalitis multiple sclerosis ms although early symptoms sarscov respiratory pathogenesis differential diagnosis always considered neurological perspective stop mortalitiespmid34967301 doi102174 1871527320666210706103422,0.0
paradoxical sexspecific patterns autoantibody response sarscov2 infection background pronounced sex differences susceptibility response sarscov2 infection remain poorly understood emerging evidence highlighted potential importance autoimmune activation modulating acute response recovery trajectories following sarscov2 exposure given immuneinflammatory activity can sexbiased setting severe covid19 illness aim study examine sexspecific autoimmune reactivity sarscov2 absence extreme clinical diseasemethodsin study assessed autoantibody aab reactivity 91 autoantigens previously linked range classic autoimmune diseases cohort 177 participants 65 women 35 men mean age 35 confirmed evidence prior sarscov2 infection based presence antibody nucleocapsid protein sarscov2 data compared 53 prepandemic healthy controls 49 women 51 men participant sociodemographic data serological analyses sarscov2 infection status covid19 related symptoms collected electronic survey questions symptoms burden score constructed based total number reported symptoms n 21 experienced within 6 months prior blood draw wherein greater number symptoms corresponded higher score assigned severe burdenresultsin multivariable analyses observed sexspecific patterns autoreactivity associated presence absence well timing clustering symptoms associated prior covid19 illness whereas overall aab response prominent women following asymptomatic infection breadth extent aab reactivity prominent men following least mildly symptomatic infection notably observed reactivity included distinct antigens molecular homology sarscov2conclusionour results reveal prior sarscov2 infection even absence severe clinical disease can lead broad aab response exhibits sexspecific patterns prevalence antigen selectivity understanding nature triggered aab activation among men women exposed sarscov2 will essential developing effective interventions immunemediated sequelae covid19,0.0
four square step test fsst multiple sclerosis ms four square step test fsst multiple sclerosis ms,0.0
activitiesspecific balance confidence abc scale multiple sclerosis ms 16item selfreport measure patients rate balance confidence performing several activities,0.0
functional reach test multiple sclerosis ms functional reach test multiple sclerosis ms,0.0
hauser ambulation index multiple sclerosis target population people multiple sclerosis ms,0.0
multiple sclerosis ms quality life inventory measures fatigue pain gait quality life role function social function,0.0
rivermead mobility index multiple sclerosis ms target population people multiple sclerosis ms,0.0
expanded disability status scale edss multiple sclerosis ms measures neurologic evaluation multiple sclerosis ms,0.0
multiple sclerosis ms functional composite msfc measures limitations unidimensionality prior existing functional status outcomes expanded disability status scale edss,0.0
berg balance scale bbs multiple sclerosis ms berg balance scale multiple sclerosis,0.0
expanded disability status scale edss measures neurologic evaluation multiple sclerosis ms,0.0
correction ofatumumab review relapsing forms multiple sclerosis drugs 2021 dec 29 doi 101007 s4026502101669w online ahead printno abstractpmid34964925 doi101007 s4026502101669w,0.0
role lipoic acid multiple sclerosis cns neurosci ther 2021 dec 28 doi 101111 cns13793 online ahead printabstractlipoic acid la endogenous antioxidant exists widely nature supplementation la promising approach improve outcomes patients multiple sclerosis ms systematic review aimed provide comprehensive overview vitro vivo studies describing pharmacokinetics efficacy safety mechanism la msrelated experiments clinical trials total 516 records identified searching five databases including pubmed web science embase scopus cochrane library overall included 20 studies reporting la effects cell mouse models ms 12 studies reporting la effects patients ms briefly cell experiments revealed la protected neurons inhibiting expression inflammatory mediators activities immune cells experimental autoimmune encephalomyelitis mouse experiments demonstrated la consistently reduced number infiltrating immune cells central nervous system decreased clinical disability scores patients ms showed relatively stable expanded disability status scale scores better walking performance adverse events oral administration la notably heterogeneity evidence existed among modeling methods la usage ms stage trial duration conclusion review provides evidence antiinflammatory antioxidative effects la vitro vivo experiments therefore patients ms may benefit la administration whether la can routine supplementary therapy warrants studypmid34964271 doi101111 cns13793,0.0
immunomodifying neuroprotective effects noscapine implications multiple sclerosis neurodegenerative psychiatric disorders chem biol interact 2021 dec 25109794 doi 101016 jcbi2021109794 online ahead printabstractnoscapine phthalide isoquinoline alkaloid antitussive activity noscapine protects oligodendroglia ischemic chemical injury binds bitter taste receptors antagonizes bradykinin histaminergic systems may benefit treatment multiple sclerosis noscapine normalizes axonal transport exerts significant therapeutic efficacy animal models parkinsons disease amyotrophic lateral sclerosis noscapine exerts neuroprotective effects oxygen glucosedeprived fetal cortical neuronal cells reduces ischemic brain damage neonatal rat pups pilot clinical studies indicated beneficial effects noscapine stroke noscapine harbours anxiolytic activity methylnoscapine blocks small conductance sk channels beneficial alleviating anxiety depression noscapine exerts anticholinesterase activity acts inhibitory inflammatory transcription factor nfb may harnessed treatment alzheimers disease bloodbrain barrier traversing features versatile actions noscapine may promising agent armamentarium neurodegenerative psychiatric diseasespmid34963564 doi101016 jcbi2021109794,1.0
converging roles psenen#x2f pen2 cln3 autophagylysosome system autophagy 2021 dec 29118 doi 101080 1554862720212016232 online ahead printabstractpsenen pen2 smallest subunit secretase complex intramembrane protease cleaves proteins within transmembrane domains mutations components secretase underlie familial alzheimer disease addition proteolytic activity supplementary secretase independent functions macroautophagy autophagylysosome system proposed screened pseneninteracting proteins identified cln3 mutations cln3 causative juvenile neuronal ceroid lipofuscinosis rare lysosomal storage disorder considered common neurodegenerative disease children mutations psenen cln3 genes cause different neurodegenerative diseases understanding shared cellular functions proteins might pertinent understanding general cellular mechanisms underlying neurodegeneration hypothesized cln3 modulates secretase activity psenen cln3 play associated roles autophagylysosome system applied crispr geneediting obtained independent isogenic hela knockout cell lines psenen cln3 following previous studies demonstrate psenen essential forming functional secretase complex indispensable secretase activity contrast cln3 modulate secretase activity significant degree observed psenen cln3knockout cells corresponding alterations autophagylysosome system include reduced activity lysosomal enzymes lysosome number increased number autophagosomes increased lysosomeautophagosome fusion elevated levels tfeb transcription factor eb study strongly suggests converging roles psenen cln3 autophagylysosome system secretase activityindependent manner supporting idea common cytopathological processes underlying different neurodegenerative diseasespmid34964690 doi101080 1554862720212016232,0.0
targeting pkc microglia promote remyelination repair cns curr opin pharmacol 2021 dec 26 62103108 doi 101016 jcoph202111008 online ahead printabstractmicroglia cnsinfiltrating macrophages play significant roles pathogenesis neuroinflammatory neurodegenerative diseases alzheimers disease parkinsons disease multiple sclerosis prolonged dysregulated inflammatory responses innate immune cells can deleterious effects surrounding cns microenvironment can worsen neurodegeneration demyelination however although chronic activation proinflammatory microglia maladaptive functional microglial subtypes play beneficial roles cns repair regeneration therefore tremendous interest understanding underlying mechanism activation reparative regenerative microglia review focus potential role pkc downstream signaling molecule trem2 plc2 pkc modulators promoting activation reparative regenerative microglial subtypes novel therapy neuroinflammatory neurodegenerative diseasespmid34965482 doi101016 jcoph202111008,1.0
humoral immune response third sarscov2 mrna vaccination cd20 depleted people multiple sclerosis vaccines basel 2021 dec 11 9 12 1470 doi 103390 vaccines9121470abstractcd20 depletion risk factor unfavorable outcomes covid19 people ms pwms evidence suggests protective igg response mrnabased vaccines b celldepleted individuals limited studied seroconversion third mrna sarscov2 vaccine b celldepleted pwms limited igg response standard immunization sixteen pwms treated ocrelizumab rituximab received third homologous sarscov2 mrna vaccine either moderna mrna1273 pfizerbiontechs bnt162b2 vaccine quantified response igg antibodies spike receptorbinding domain sarscov2 four weeks later antibody titer 100 au ml considered clinically relevant median time last infusion anticd20 treatment third vaccination 229 weeks range 151313 third vaccination one 16 patients showed igg titer deemed clinically relevant seroconverted patient measurable bcell counts time third vaccination development humoral immune response remains rare pwms anticd20 therapy even third dose homologous sarscov2 mrna vaccine remains determined whether tcell responses can compensate lack seroconversion provide sufficient protection cov2 infectionspmid34960216 doi103390 vaccines9121470,0.0
study protocol occupational rehabilitation multiple sclerosis sensors basel 2021 dec 17 21 24 8436 doi 103390 s21248436abstractdigital medical solutions can helpful restorative neurology allow patients practice rehabilitation activities remotely work discloses removes iomt system providing telemedicine services context multiple sclerosis rehabilitation within frame project storms rehabilitative protocol exercises can provided removes services integrated individual rehabilitation project designed remote multidimensional medical team present manuscript first phase study described including definition needs addressed employed technology design development exergames possible practical professional academic consequences storms project implemented aim act starting point development digital telerehabilitation solutions support multiple sclerosis patients improving living conditions paper introduces study protocol addresses preclinical research needs system issues can studied better understood might addressed also includes tools favor remote patient monitoring support clinical staffpmid34960529 doi103390 s21248436,0.0
lactate threshold training program patients multiple sclerosis multidisciplinary approach nutrients 2021 nov 27 13 12 4284 doi 103390 nu13124284abstractphysical activity play key role improving quality life particularly patients nervous system diseases multiple sclerosis ms lactacid anaerobic training study aims investigate effects biopsychophysical level counteract chronic fatigue associated pathology improve mental health psychological neurotrophic level eight subjects age 3488 445 years affected multiple sclerosis involved lactate threshold training program administered biweekly 12 weeks beginning study t0 end study t1 9 months end study t2 physical psychological hematochemicals parameters dietary habits tested results obtained confirmed lactacid exercise can influence brainderived neurotrophic factor bdnf levels well dehydroepiandrosterone sulfate dheas levels addition levels baseline lactate best used energy substrate showed decrease protocol training selfefficacy regarding worries concerns management significantly increased t0 t1 eating attitudes test eat26 highlight eating disease patients normal diet enrolled study physical exercise also greatly influenced patients psychologically emotionally increasing selfesteem lactate threshold training together dietary habits appears exert synergic positive effects inflammation neural plasticity neuroprotection producing preventive effects ms symptoms progressionpmid34959834 doi103390 nu13124284,0.0
role trpa1 channels central processing odours contributing behavioural responses mice pharmaceuticals basel 2021 dec 20 14 12 1336 doi 103390 ph14121336abstracttransient receptor potential ankyrin 1 trpa1 nonselective cation channel contributes several patho physiological processes smell loss early sign several neurodegenerative disorders multiple sclerosis parkinsons alzheimers diseases therefore focused role olfaction social behaviour aim reveal potential therapeutic use presence trpa1 mrna studied along olfactory tract mice combined rnascope situ hybridisation immunohistochemistry aversive effects fox cat odour examined parallel stress hormone levels vitro calcium imaging applied test substances can directly activate trpa1 receptors role trpa1 social behaviour investigated comparing trpa1 wildtype knockout mice ko trpa1 mrna detected olfactory bulb piriform cortex expression weak olfactory epithelium fox cat odour directly activated trpa1 channels trpa1overexpressing chinese hamster ovary cell lines accordingly ko animals showed less aversion fox cat odour social interest ko mice reduced social habituationdishabituation social interaction residentintruder tests trpa1 may contribute odour processing several points olfactory tract may play important role shaping social behaviour mice thus trpa1 may influence development certain social disorders serving potential drug target futurepmid34959735 doi103390 ph14121336,0.0
tibolone restrains neuroinflammation mouse experimental autoimmune encephalomyelitis j neuroendocrinol 2021 dec 9e13078 doi 101111 jne13078 online ahead printabstractmultiple sclerosis ms immunemediated degenerating disease myelin sheaths damaged result chronic progressive inflammation central nervous system tibolone 7 17 17hydroxy7methyl19norpregn5 10 en20in3one synthetic estrogenic compound tissuespecific actions used menopausal hormone therapy shows neuroprotective antioxidant properties vivo vitro present study analyzed whether tibolone plays therapeutic role experimental autoimmune encephalomyelitis eae mice commonly used model ms female c57bl 6 mice induced myelin oligodendrocyte glycoprotein mog3555 received sc tibolone 008 mg kg1 injection every day day induction death acute phase disease reactive gliosis toll like receptor 4 tlr4 high mobility group box protein 1 hmgb1 inflammasome parameters activated akt levels myelin assessed realtime polymerase chain reaction immunohistochemistry western blot analysis findings indicated eae spinal cord tibolone reversed astrocytic microglial reaction reduced hyperexpression tlr4 hmgb1 well nlr family pyrin domain containing 3caspase 1interleukin1 inflammasome activation time tibolone attenuated akt nuclear factor kappa b pathway limited white matter demyelination area estrogen receptor expression unaltered tibolone treatment clinically tibolone improved neurological symptoms without uterine compromise overall data suggest tibolone may serve promising agent attenuation msrelated inflammationpmid34961984 doi101111 jne13078,1.0
b cell modulation anticd79bantibodies ameliorates experimental autoimmune encephalitis mice eur j immunol 2021 dec 28 doi 101002 eji202149523 online ahead printabstractb cells play major role pathogenesis many autoimmune diseases like multiple sclerosis rheumatoid arthritis systemic lupus erythematosus depletion b cells anticd20 antibodies established therapy multiple sclerosis however total b cell depletion will also affect regulatory b cells known suppress autoimmune responses studies describe alternative approach based targeting cd79b induces partial b cell depletion achieves therapeutic effects b cell modulation prophylactic therapeutic treatment antibody cd79b also deglycosylated variant antibody lacking effector function like antibodydependent cellular cytotoxicity complement activation significantly reduced development progression experimental autoimmune encephalitis eae mice data show modulation b cells via cd79b equally effective almost complete b cell depletion anticd20 antibodies may constitute alternative approach treat multiple sclerosis article protected copyright rights reservedpmid34962287 doi101002 eji202149523,0.0
diet quality assessment wheelchair users multiple sclerosis nutrients 2021 dec 3 13 12 4352 doi 103390 nu13124352abstractbackground diet quality distinctively examined wheelchair users multiple sclerosis ms methods crosssectional study examined diet history questionnaire dhq iii automated selfadministered 24h asa24 dietary assessment tool 128 wheelchair users ms participants prompted complete dhqiii 3 asa24 recalls sevenday data collection period healthy eating index hei 2015 scores calculated dhqiii asa24 scores compared normative values spearmans correlation analyses rs estimated associations dhqiii asa24 hei2015 total component scores supportive paired sample ttestsresults hei2015 scores dhqiii asa24 significantly higher normative values total score total protein foods added sugar correlations hei2015 scores generated using asa24 dhqiii statistically significant range rs 023069 however significant differences asa24 dhqiii values noted hei2015 total score total fruits whole fruit total vegetable greens beans whole grains seafood plant protein refined grains saturated fatsconclusion study provided novel description diet quality wheelchair users ms guiding future research promoting healthy eating populationpmid34959904 doi103390 nu13124352,0.0
highfidelity fast volumetric brain mri using synergistic wavecontrolled aliasing parallel imaging hybrid denoising generative adversarial network hdngan med phys 2021 dec 27 doi 101002 mp15427 online ahead printabstractpurpose goal study leverage advanced fast imaging technique wavecontrolled aliasing parallel imaging wavecaipi generative adversarial network gan denoising achieve accelerated highquality highsignaltonoiseratio snr volumetric mrimethods threedimensional 3d t2 weighted fluidattenuated inversion recovery flair image data acquired 33 multiple sclerosis ms patients using prototype wavecaipi sequence acceleration factor r 32 275 minutes standard t2 space flair sequence r 2 725 minutes hybrid denoising gan entitled hdngan consisting 3d generator 2d discriminator proposed denoise highly accelerated wavecaipi images hdngan benefits improved image synthesis performance provided 3d generator increased training samples limited number patients training 2d discriminator hdngan trained validated data 25 ms patients standard flair images target evaluated data 8 ms patients seen training hdngan compared denoising methods including aonlm bm4d munet 3d gan qualitative quantitative analysis output images using mean squared error mse vgg perceptual loss compared standard flair images reader assessment two neuroradiologists regarding sharpness snr lesion conspicuity overall quality finally performance denoising methods compared higher noise levels using simulated data added rician noiseresults hdngan effectively denoised lowsnr wavecaipi images sharpness rich textural details adjusted controlling contribution adversarial loss total loss training generator quantitatively hdngan 103 achieved low mse lowest vgg perceptual loss reader study showed hdngan 103 significantly improved snr wavecaipi images p0001 outperformed aonlm p 0015 bm4d p0001 munet p0001 3d gan 103 p0001 regarding image sharpness outperformed munet p0001 3d gan 103 p 0001 regarding lesion conspicuity overall quality score hdngan 103 425043 significantly higher wavecaipi 369046 p 0003 bm4d 350071 p 0001 munet 325075 p0001 3d gan 103 350050 p0001 significant difference compared standard flair images 438048 p 0333 advantages hdngan methods obvious higher noise levelsconclusion hdngan provides robust feasible denoising preserving rich textural detail empirical volumetric mri data study using empirical patient data systematic evaluation supports use hdngan combination modern fast imaging techniques wavecaipi achieve highfidelity fast volumetric mri represents important step clinical translation gans article protected copyright rights reservedpmid34961944 doi101002 mp15427,0.0
association immune dysfunction covid19 breakthrough infection sarscov2 vaccination us jama intern med 2021 dec 28 doi 101001 jamainternmed20217024 online ahead printabstractimportance persons immune dysfunction higher risk severe covid19 outcomes however patients largely excluded sarscov2 vaccine clinical trials creating large evidence gapobjective identify incidence rate incidence rate ratio irr covid19 breakthrough infection sarscov2 vaccination among persons without immune dysfunctiondesign setting participants retrospective cohort study analyzed data national covid cohort collaborative n3c partnership developed secure centralized electronic medical recordbased repository covid19 clinical data academic medical centers across us persons received least 1 dose sarscov2 vaccine december 10 2020 september 16 2021 included samplemain outcomes measures vaccination covid19 diagnosis immune dysfunction diagnoses ie hiv infection multiple sclerosis rheumatoid arthritis solid organ transplant bone marrow transplantation comorbid conditions demographic data accessed n3c data enclave breakthrough infection defined covid19 infection contracted 14th day vaccination risk full partial vaccination assessed patients without immune dysfunction using poisson regression robust ses poisson regression models controlled study period pre postdelta variant june 20 2021 full vaccination status covid19 infection vaccination demographic characteristics geographic location comorbidity burdenresults total 664 722 patients n3c sample included patients median iqr age 51 3466 years predominantly women n 378 307 569 overall incidence rate covid19 breakthrough infection 50 per 1000 personmonths among fully vaccinated persons higher delta variant became dominant sarscov2 strain incidence rate vs june 20 2021 22 95 ci 2222 vs 73 95 ci 7374 per 1000 personmonths compared partial vaccination full vaccination associated 28 reduced risk breakthrough infection adjusted irr airr 072 95 ci 068076 people breakthrough infection full vaccination likely older women people hiv infection airr 133 95 ci 118149 rheumatoid arthritis airr 120 95 ci 109132 solid organ transplant airr 216 95 ci 196238 higher rate breakthrough infectionconclusions relevance cohort study found full vaccination associated reduced risk covid19 breakthrough infection regardless immune status patients despite full vaccination persons immune dysfunction substantially higher risk covid19 breakthrough infection without condition persons immune dysfunction continued use nonpharmaceutical interventions eg mask wearing alternative vaccine strategies eg additional doses immunogenicity testing recommended even full vaccinationpmid34962505 doi101001 jamainternmed20217024,0.0
current take systemic sclerosis patients#39 vaccination recommendations vaccines basel 2021 dec 2 9 12 1426 doi 103390 vaccines9121426abstractsystemic sclerosis ssc rare autoimmune inflammatory rheumatic disease prevalence ssc ranges 7 700 cases per million worldwide due multiple organ involvement constant inflammatory state group patients presents increased risk infectious diseases paper aimed gather uptodate evidence vaccination strategies patients ssc useful tool prevention management infectious diseases authors conducted scoping review paragraph presents data specific vaccines safety immunogenicity efficacy work deals following topics sarscov2 seasonal influenza s pneumoniae hav hbv hzv n meningitidis h influenzae hpv diphtheriatetanuspertussispmid34960174 doi103390 vaccines9121426,0.0
effect ketogenic diet quality life adults chronic disease systematic review randomized controlled trials nutrients 2021 dec 14 13 12 4463 doi 103390 nu13124463abstractbackground chronic diseases adversely affect quality life qol ketogenic diet kd may improve qolobjective aim systematic review summarize available evidence randomized controlled trials rcts establish effect kd qol adults chronic diseasesmethods reporting followed prisma guidelines included randomized controlled trials rcts conducted adults chronic disease including intervention group received kd control group qol reported outcome searched pubmed apa psycinfo embase cumulative index nursing allied health literature cinahl cochrane library clinicaltrialsgov references included articles previous relevant reviews without language time restrictions critically appraised included studies narratively synthesized findingsresults nine rcts included risk bias low except allocation concealment blinding patients cancer one rct found improvement overall qol another reported improved physical component summary one found superiority kd qol domains patients neurological disorders improved qol reported alzheimers disease patients whereas difference mental physical health qol noted patients multiple sclerosis patients obesity type ii diabetes one rct reported superiority energyrestricted kd improving role functioning mental health health perceptions pain compared guidelinebased diet whereas another rct high low carbohydrate diets achieved comparable improvements among patients knee osteoarthritis differences kd lowfat groups noted dietary compliance kd reported three studies shown high side effects mostly noted first weeks intervention adverse events markedly different kd comparison dietconclusions evidence rcts investigating effect kd qol adults chronic disease inconclusive promising effect noted included studies low rates adverse events side effects encourage future investigations regardpmid34960015 doi103390 nu13124463,0.0
cystectomy ileal conduit neurogenic bladder comparison open laparoscopic robotic approaches neurourol urodyn 2021 dec 28 doi 101002 nau24855 online ahead printabstractaim objective present study compare outcomes open versus laparoscopic versus robotic cystectomy ileal conduit neurogenic lower urinary tract dysfunction nlutd methods charts patients underwent cystectomy ileal conduit nlutd january 2004 november 2020 academic center retrospectively reviewed approach either open laparoscopic robotassisted depending period ie three consecutive era robotic approach diversion done either intracorporeally extracorporeally compared perioperative late postoperative outcomes three groupsresults exclusion 10 patients nonneurogenic benign conditions 126 patients included study period frequent neurological conditions multiple sclerosis 365 spinal cord injury 254 approach open laparoscopic robotassisted 31 246 26 206 69 547 cases respectively seventytwo patients experienced 90day postoperative complication 571 22 major complication clavien 3 higher 175 including one death 08 rate major postoperative complications significantly lower robotic group 23 vs 23 vs 10 p 0049 rate overall complications comparable across three groups 581 vs 539 vs 606 p 084 median followup 23 months 22 patients presented late complication 176 mainly incisional hernia 5 4 ureteroileal stricture 9 72 rate late complications differ significantly three approachesconclusion cystectomy ileal conduit neurogenic bladder associated relatively high perioperative morbidity robotassisted approach may decrease risk major postoperative complicationspmid34962653 doi101002 nau24855,0.0
vitamin d supplementation mental health multiple sclerosis patients systematic review nutrients 2021 nov 24 13 12 4207 doi 103390 nu13124207abstractvitamin d promising role multiple sclerosis ms management found beneficial patients mental health reduced ms patients aim present study conduct systematic review literature assess influence vitamin d supplementation mental health ms patients systematic review registered prospero database crd42020155779 conducted basis prisma guidelines search procedure conducted using pubmed web science databases included studies published september 2021 six studies included systematic review risk bias analyzed using newcastleottawa scale nos within included studies two studies randomized placebo four prospective studies studies presented vitamin d interventions randomized placebo randomized supplementation applied various durationsfrom 4 weeks 12 months studies compared patients applied vitamin d supplementation apply verified effect supplementation number years mental health outcomes assessed included quality life depression depressive symptoms fatigue additional element majority studies supported positive influence vitamin d mental health ms patients including study characterized highest quality randomized placebo highest nos score studies assessed quality life indicated positive influence vitamin d studies find positive influence vitamin d conducted depression depressive symptoms spite fact small number studies conducted far two studies randomized placebo conclusions may formulated systematic review allowed us conclude may positive effect vitamin d supplementation ms patients stated studies analyzing quality life well one study analyzing depressive symptoms considering vitamin d deficiency common ms patients potential positive influence supplementation quality life supplementation applied least doses cover recommended intakepmid34959758 doi103390 nu13124207,0.0
nanotechnologybased drug delivery strategies repair mitochondrial function neuroinflammatory neurodegenerative diseases pharmaceutics 2021 dec 1 13 12 2055 doi 103390 pharmaceutics13122055abstractmitochondria vital organelles eukaryotic cells control diverse physiological processes related energy production calcium homeostasis generation reactive oxygen species cell death several studies demonstrated structural functional mitochondrial disturbances involved development different neuroinflammatory ni neurodegenerative nd diseases nindds multiple sclerosis alzheimers disease parkinsons disease huntingtons disease amyotrophic lateral sclerosis remarkably counteracting mitochondrial impairment genetic pharmacologic treatment ameliorates neurodegeneration clinical disability animal models diseases therefore development nanosystems enabling sustained selective delivery mitochondriatargeted drugs novel effective strategy tackle nindds review outline impact mitochondrial dysfunction associated unbalanced mitochondrial dynamics altered mitophagy oxidative stress energy deficit proteinopathies nindds addition review different strategies selective mitochondriaspecific ligand targeting discuss novel nanomaterials nanozymes drugloaded nanosystems developed repair mitochondrial function therapeutic benefits protecting oxidative stress restoring cell energy production preventing cell death inhibiting protein aggregates improving motor cognitive disability cellular animal models different ninddspmid34959337 doi103390 pharmaceutics13122055,0.0
aptamer applications neuroscience pharmaceuticals basel 2021 dec 3 14 12 1260 doi 103390 ph14121260abstractbeing predominant cause disability neurological diseases received much attention global health community billion people suffer one following neurological disorders dementia epilepsy stroke migraine meningitis alzheimers disease parkinsons disease multiple sclerosis amyotrophic lateral sclerosis huntingtons disease prion disease brain tumors diagnosis treatment options limited many diseases aptamers small nonimmunogenic nucleic acid molecules easy chemically modify offer potential diagnostic theragnostic applications meet needs review covers pioneering studies applying aptamers shows promise future diagnostics treatments neurological disorders pose increasingly dire worldwide health challengespmid34959661 doi103390 ph14121260,0.0
combining human genetics multiple sclerosis oxidative stress phenotype drug repositioning pharmaceutics 2021 dec 2 13 12 2064 doi 103390 pharmaceutics13122064abstractin multiple sclerosis ms oxidative stress os implicated neurodegenerative processes occur beginning disease unchecked os initiates vicious circle caused crosstalk inflammation leading demyelination axonal damage neuronal loss failure ms antioxidant therapies relying use endogenous natural compounds drives application novel approaches assess target relevance disease prior preclinical testing new drug candidates identify drugs can act regulators intracellular oxidative homeostasis applied silico approach links genomewide ms associations molecular quantitative trait loci qtls proteins os pathway found 10 drugs central nervous system oral bioavailability targeting five 21 topscoring hits including arginine methyltransferase carm1 first linked ms particular direction brain expression qtls carm1 protein kinase mapk1 enabled us select biib021 peitc drugs required target modulation study highlights osrelated molecules regulated functional ms variants targeted existing drugs supplement approved diseasemodifying treatmentspmid34959343 doi103390 pharmaceutics13122064,1.0
myelin peptidemannan conjugate multiple sclerosis vaccines conjugation efficacy stability vaccine ingredient vaccines basel 2021 dec 8 9 12 1456 doi 103390 vaccines9121456abstractmyelin peptidemannan conjugates shown potential vaccines immunotherapy multiple sclerosis conjugates comprised epitope peptide polysaccharide mannan transfers carrier antigenic peptide dendritic cells process present antigenic peptides surface complex mhc class class ii resulting tcell stimulation conjugation antigenic peptide mannan occurs linker lysgly 5 connects peptide oxidized mannose units mannan study describes novel methods quantification vaccine ingredient peptide within conjugate prerequisite approval clinical trials pursuit multiple sclerosis therapeutics myelin peptides mog3555 mbp8399 plp131145 linear cyclic form altered peptide ligands conjugated appropriate carriers possess immunomodulatory properties experimental models potential candidates clinical trialspmid34960201 doi103390 vaccines9121456,1.0
patch individual filter layers cnns harness spatial homogeneity neuroimaging data sci rep 2021 dec 27 11 1 24447 doi 101038 s41598021037859abstractconvolutional neural networks cnns type deep learninghave specifically designed highly heterogeneous data natural images neuroimaging data however comparably homogeneous due 1 uniform structure brain 2 additional efforts spatially normalize data standard template using linear nonlinear transformations harness spatial homogeneity neuroimaging data suggest new cnn architecture combines idea hierarchical abstraction cnns prior spatial homogeneity neuroimaging data whereas early layers trained globally using standard convolutional layers introduce patch individual filters pif higher abstract layers learning filters individual latent space patches without sharing weights pif layers can learn abstract features faster specific regions thoroughly evaluated pif layers three different tasks data sets namely sex classification uk biobank data alzheimers disease detection adni data multiple sclerosis detection private hospital data compared two baseline models standard cnn patchbased cnn obtained two main results first cnns using pif layers converge consistently faster measured run time seconds number iterations baseline models second standard cnn pif model outperformed patchbased cnn terms balanced accuracy receiver operating characteristic area curve roc auc maximal balanced accuracy roc auc 9421 9910 sex classification task pif model 8124 8048 8889 8735 respectively alzheimers disease multiple sclerosis detection tasks standard cnn model conclusion demonstrated cnns using pif layers result faster convergence obtaining predictive performance standard cnn best knowledge first study introduces prior form inductive bias harness spatial homogeneity neuroimaging datapmid34961762 doi101038 s41598021037859,0.0
quantified hemodynamic parameters venous system multiple sclerosis systematic review abstractbackground multiple sclerosis ms complex neurodegenerative condition influenced combination genetic environmental factors included factors venous system however extent influences etiology ms yet fully characterised aim review critically summarise literature available concerning venous system ms primarily concerning specific data venous pressure blood flow systemmethods systematic review conducted application preferred reporting items systematic reviews metaanalyses prisma criteria advanced search functions scopus pubmed databases used conduct literature search resulting 136 unique articles initially identified applying relevant exclusion criteria 22 studies chosen reviewresults selected studies analysed venous pressure blood flow related findings 14 studies contributing data internal jugular vein ijv flow rate 5 blood flows intracranial venous sinuses 2 blood flow pulsatility 6 supplying information relevant venous pressure 3 studies contributed multiple areas general findings review included ijv flow significantly different ms patients controls however variances stenotic s nonstenotic ns ms patients due limited data two areas defined review research required establish variances ms presentconclusion remains unclear significant differences many flow variables ms patients controls considered review advantageous future work area focused understanding hemodynamics system primarily concerning flow rate venous pressure vascular resistance related impact factors etiology ms,0.0
efficacy technologybased clientcentred training system neurological rehabilitation randomised controlled trial background clientcentred taskoriented approach advantages towards motivation adherence therapy neurorehabilitation costly integrate practice intelligent activitybased clientcentred training iact lowcost kinectbased system developed integrates clientcentred taskoriented approach objectives 1 investigate effect additional iact training functioning 2 assess whether training iact resulted goal oriented trainingmethodsa singleblind randomised controlled trial performed 4 belgian rehabilitation centres persons central nervous system deficits participants randomly allocated independent websitebased code generator using blocked randomisation n 4 intervention control group intervention group received conventional care additional training iact 3 45 min week 6 weeks control group received solely conventional care functional ability performance quality life qol fatigue trunk movement shoulder active range motion arom assessed baseline 3 weeks 6 weeks training 6 weeks cessation training data analysed using nonparametric within group analysisresults47 persons randomised 45 analysed intervention n 25 control n 22 group improved time functional ability performance measured wolf motor function test manual ability measure36 canadian occupational performance measure major differences found groups primary outcome measures regarding qol fatigue trunk movement shoulder arom significant group differences found high adherence iact training found ie 9792 adverse events linked iact reported intervention group amount trained personal goals 88 much higher control group 46 conclusionsalthough additional use iact statistically significant added value regarding functional outcome conventional therapy additional iact training provides individualised clientcentred therapy adherence towards iact training high higher intensity iact training may increase therapy effects investigated future researchtrial registration clinicaltrialsgov identifier nct02982811 registered 29 november 2016,0.0
prevalence trigeminal neuralgia multiple sclerosis systematic review metaanalysis abstractbackgroundthe prevalence trigeminal neuralgia tn patients diagnosed multiple sclerosis ms insufficiently understood controversially reported study focused providing better understanding prevalence tn ms patientsmethodwe systematically searched pubmed scopus embase web science google scholar identify studies published january 1 1990 december 30 2020 included studies reporting tn prevalence among ms patients exclude case reports series editorial studies review studies nonenglish written articles used pooled prevalence estimates determine tn prevalence among ms patientsresultspooled overall tn prevalence among 19 studies 30 348 ms patients estimated 34 95 ci 1559 high level heterogeneity among studies i29892 p0001 pooled prevalence tn male female patients across 9 surveys 24 95 ci 0554 38 95 ci 0887 respectively heterogeneity two groupswas observed p0558 metaregression performed explore source heterogeneity none candidate covariates including year study publication sample size average age patients disease duration significant modelconclusionour results showed tn common problem among patients ms predominantly male patients future studies target general prevalence pain ms patients,0.0
examining transcranial random noise stimulation addon treatment persistent symptoms schizophrenia stimzo study protocol multicentre doubleblind randomized shamcontrolled clinical trial background one three patients schizophrenia failed respond adequately antipsychotics continue experience debilitating symptoms auditory hallucinations negative symptoms development additional therapeutic approaches persistent symptoms constitutes major goal patients develop randomizedcontrolled trial testing efficacy highfrequency transcranial random noise stimulation hftrns treatment resistant persistent symptoms schizophrenia patients various profiles symptoms cognitive deficits illness duration also aim investigate biological cognitive effects hftrns identify predictors clinical responsemethodsin randomized doubleblind 2arm parallelgroup controlled multicentre study 144 patients schizophrenia persistent symptoms despite prescription least one antipsychotic treatment will randomly allocated receive either active n 72 sham n 72 hftrns hftrns 100500 hz will delivered 20 min current intensity 2 ma 1ma offset twice day 5 consecutive weekdays anode will placed left dorsolateral prefrontal cortex cathode left temporoparietal junction patients symptoms will assessed prior hftrns baseline 10 sessions 1 3 6month followup primary outcome will number responders defined reduction least 25 baseline scores positive negative syndrome scale panss 10 sessions secondary outcomes will include brain activity connectivity source monitoring performances social cognition clinical including auditory hallucinations biological variables attitude toward treatmentdiscussionthe results trial will constitute first step toward establishing usefulness hftrns schizophrenia whatever stage illness level treatment resistance hypothesize longlasting effect active hftrns severity schizophrenia symptoms compared sham trial will also implications use hftrns preventive intervention relapse patients schizophreniatrial registrationclinicaltrialsgov nct02744989 prospectively registered 20 april 2016,0.0
energeyeze visionspecific ehealth intervention based cognitive behavioral therapy selfmanagement reduce fatigue adults visual impairment study protocol randomized controlled trial background half adults visual impairment experience severe symptoms fatigue negative impact daily life since evidencebased treatment reduce fatigue adults visual impairment developed energeyeze ehealth intervention based cognitive behavioral therapy selfmanagement tailored needs visually impaired adults aim describe study protocol randomized controlled trial testing energeyezemethodsa randomized controlled trial will conducted investigate costeffectiveness costutility energeyeze reduce fatigue severity compared care usual healthcare societal perspective total 172 severely fatigued adults visual impairment will recruited randomized either energeyeze intervention plus care usual care usual ratio 11 inclusion criteria visual impairment experiencing severe fatigue checklist individual strength subscale fatigue severity cisfs 35 18 years older understanding dutch language access internet intervention consists one facetoface session computer training followed internetbased modules information assignments coping fatigue 5month intervention participants will digitally supported social worker measurements will administered baseline 6 12 months additionally related costeffectiveness 3 9 months primary outcome fatigue severity cisfs discussionsevere fatigue top visual impairment compromises quality life associated incremental societal costs largely determine economic burden low vision blindness energeyeze contributes evidence base potentially feasible interventions reduce important healthrelated consequences vision loss fulfill gap knowledge skills treatment options low vision servicestrial registrationdutch trial register ntr7764 registered 28 may 2019,0.0
epilepsia partialis continua relapsingremitting multiple sclerosis possible distinct relapse phenotype clin neurol neurosurg 2021 dec 21 213107099 doi 101016 jclineuro2021107099 online ahead printabstractepilepsia partialis continua epc rare phenomenon multiple sclerosis ms describe patient relapsingremitting ms three episodes epc refractoriness antiseizure drugs corticosteroidresponsiveness lesions likely attributable episodes epc seen 15 tesla mri hypothesize due small volume presumed cortical juxtacortical lesions involving primary motor cortex association relapsingremitting disease corticosteroid responsiveness dissemination episodes epc space time patient suggest epc may represent distinct relapse phenotype mspmid34959105 doi101016 jclineuro2021107099,0.0
predictors fatigue selfmanagement behaviors adults multiple sclerosis neurorehabilitation 2021 dec 20 doi 103233 nre210179 online ahead printabstractbackground fatigue one common disabling symptoms people multiple sclerosis ms fatigue selfmanagement behaviors may effective reducing impact fatigue people ms however studies examined factors influence engagement fatigue selfmanagement behaviorsobjective identify factors directly indirectly influence fatigue selfmanagement behaviorsmethods participants ms n 300 completed online questionnaires baseline 6weeks using self family management framework examined influence health status resources environment healthcare utilization selfmanagement processes fatigue selfmanagement behaviors 6weeks multiple regression path analyses conductedresults final regression model variables accounted 4158 variance fatigue selfmanagement behavior included outcome expectation 0287 disability 0265 environmental barriers 0188 selfefficacy 0153 symptom severity 0113 living rural community 0108 living alone 0103 path analysis indicated outcome expectations may mediate relationship disability levels fatigue selfmanagement behaviorconclusions health status ie disability symptom severity environmental factors eg living situation selfmanagement processes ie selfefficacy outcome expectations may play important role influencing engagement fatigue selfmanagement behaviorspmid34957957 doi103233 nre210179,0.0
probable encephalopathy spasticity multiple sclerosis patient following carbapenem administration case report brief literature review j pharm pract 2021 dec 278971900211063277 doi 101177 08971900211063277 online ahead printabstractpurpose purpose case report describe spasticity encephalopathy developed multiple sclerosis patient following carbapenem administration summary 55yearold female multiple sclerosis developed spasticity encephalopathy within 24 hours meropenem ertapenem administration second time developed encephalopathy following carbapenem administration patient gradually recovered four days following discontinuation carbapenem therapy conclusion carbapenem neurotoxicity welldocumented adverse effect linked several risk factors including central nervous system lesions despite little evidence describing risk neurotoxicity patients multiple sclerosis important understand potential adverse effects carbapenems specific patient populations help guide appropriate treatment infectionspmid34958618 doi101177 08971900211063277,0.0
opportunities obstacles associated sequential immune reconstitution therapy multiple sclerosis case report front neurol 2021 dec 8 12664596 doi 103389 fneur2021664596 ecollection 2021abstractcladribine effective diseasemodifying treatment relapsingremitting multiple sclerosis acts immune reconstitution therapy administered pulsed manner despite efficacy severe disease reactivation early treatment represents serious clinical problem clear evidence guide management situation lacking describe case patient experiencing considerable disease activity 1st year initiation cladribine treatment patient switched alemtuzumab therefore received double immune reconstitution therapy data regarding approach lacking realworld observations may interest despite achieving good control disease activity observed several serious infectious complications results suggest sequential immune reconstitution therapies may effective however price higher susceptibility infectionspmid34956035 pmcpmc8692884 doi103389 fneur2021664596,0.0
effect different diseasemodifying therapies humoral response bnt162b2 vaccine sardinian multiple sclerosis patients front immunol 2021 dec 9 12781843 doi 103389 fimmu2021781843 ecollection 2021abstractobjectives vaccination covid19 highly recommended patients affected multiple sclerosis ms however impact ms diseasemodifying therapies dmts immune response following vaccination partially investigated aimed elucidate effect dmts humoral immune response mrnabased antisarscov2 vaccines ms patientsmethods obtained sera 912 sardinian ms patients 63 healthy controls 30 days second dose bnt162b2 vaccine tested sarscov2 response using antispike s proteinbased serology previous sarscov2 infection assessed antinucleocapsid n serology patients either untreated undergoing treatment total 13 different dmts differences treatment groups comprised least 10 patients assessed generalized linear mixedeffects model demographic clinical data smoking status analyzed additional factors potentially influencing humoral immunity covid19 vaccineresults ms patients treated natalizumab teriflunomide azathioprine fingolimod ocrelizumab rituximab showed significantly lower humoral responses compared untreated patients observe statistically significant difference response patients treated drugs dimethyl fumarate interferon alemtuzumab glatiramer acetate untreated patients addition older age male sex active smoking significantly associated lower antibody titers sarscov2 ms patients previously infected sarscov2 significantly higher humoral responses vaccine uninfected patientsconclusion humoral response bnt162b2 significantly influenced specific dmts followed patients well factors previous sarscov2 infection age sex smoking status results important inform targeted strategies prevent clinically relevant covid19 ms patientspmid34956211 pmcpmc8697018 doi103389 fimmu2021781843,0.0
autoimmune#x2f paraneoplastic encephalitis antibody biomarkers frequency age sex associations mayo clin proc 2021 dec 23s00256196 21 006510 doi 101016 jmayocp202107023 online ahead printabstractobjective determine frequency detection age sex associations autoimmune paraneoplastic encephalitis antibody biomarkers aeabs methods 42 032 patients tested mayo clinic neuroimmunology laboratory january 2018 december 2019 aeabs serum cerebrospinal fluid csf including nmdarigg amparigg gababrigg caspr2igg lgi1igg gad65igg crmp5igg amphiphysinigg pca1 2 triggs anna1 2 3iggs gfapigg mglur1igg dppxigg mogigg1 results examined determine frequency antibody positivity age sex associations examined multivariable logistic regressionresults adult serum analysis 22 472 patients 56 female revealed 814 36 positive nmdarigg 246 gad65igg 215 lgi1igg 205 others children 5649 50 female 251 44 positive nmdarigg 531 mogigg1 32 gad65igg 71 others adult csf analysis 18 745 patients 54 female revealed 796 42 positive nmdarigg 397 gad65igg 285 lgi1igg 114 others children 5136 50 female 282 55 positive nmdarigg 881 gad65igg 87 others age younger 20 years associated nmdarigg mogigg1 odds ratio 811 784 respectively p001 age older 65 years associated gababrigg lgi1igg caspr2igg anna1igg 733 1498 367 1453 p001 women accounted 60 nmdarigg csf 78 gad65igg csf serum cohorts 132 p002 223 p001 respectively men accounted 62 lgi1igg cohort 187 p001 age sex interacted nmdarigg particularly female patients younger 20 years 772 p001 conclusion frequent aeabs detected nmdarigg gad65igg lgi1igg mogigg1 age sex associations may suggest paraneoplastic aging influences neurologic autoimmunitypmid34955239 doi101016 jmayocp202107023,0.0
recommendations traveling altitude neurological disorders j cent nerv syst dis 2021 dec 20 1311795735211053448 doi 101177 11795735211053448 ecollection 2021abstractbackground several neurological conditions might worsen exposure high altitude ha aim review summarize available knowledge neurological ha illnesses risk people neurological disorders attend ha locationsmethods search literature conducted several neurological disorders pubmed databases since 1970 neurological conditions searched migraine different cerebrovascular disease intracranial space occupying mass multiple sclerosis peripheral neuropathies neuromuscular disorders epileptic seizures delirium dementia parkinsons disease pd results attempts made classify risk posed condition provide recommendations regarding medical evaluation advice traveling altitude individual cases advised careful examination risk evaluation performed either outpatient mountain medicine service physician knowledge ha risks preliminary diagnostic methods anticipation neurological complications neededconclusions recommendations suggest absolute contraindications ha exposure following neurological conditions 1 unstable conditionssuch recent strokes 2 diabetic neuropathy 3 transient ischemic attack last month 4 brain tumors 5 neuromuscular disorders decrease forced vital capacity 60 consider following relative contraindications decision made case case 1 epilepsy based recurrence seizure stabilization therapy 2 pd obstructive sleep apnea syndromeosas 3 mild cognitive impairment osas 4 patent foramen ovale migraine considered risk factors acute mountain sicknesspmid34955663 pmcpmc8695750 doi101177 11795735211053448,0.0
original articlequantifying upperlimb motor impairment people multiple sclerosis physiological profiling approach ann phys rehabil med 2021 dec 24101625 doi 101016 jrehab2021101625 online ahead printabstractbackground upperlimb sensory motor impairments common people multiple sclerosis ms yet current gold standard criteria documenting functional impairment largely focuses mobility balance postural stabilityobjective aimed determine validity upperlimb physiological profile assessment ppa people ms investigating whether included domains muscle strength dexterity arm stability position sense skin sensation bimanual coordination 1 sensitive differentiating people ms healthy controls 2 correlate validated measure upperlimb function scale quantifying disability msmethods crosssectional study 40 participants ms 80 healthy controls completed 13 upperlimb ppa tests within single sessionresults people ms impaired across physiological domains tested performance 4 13 tests correlated validated measure selfreported upperlimb function pearsons r spearmans rho 03330441 whereas 3 tests associated degree msspecific disability spearmans rho 0318 0456 conclusions upperlimb ppa offers valid clinically suitable assessment upperlimb function people ms clinicians prioritise assessments motor speed fine motor control functional tasks assessment upperlimb function people ms domains commonly significantly impairedpmid34958919 doi101016 jrehab2021101625,0.0
long noncoding rna associated competing endogenous rna axes tcells multiple sclerosis front immunol 2021 dec 8 12770679 doi 103389 fimmu2021770679 ecollection 2021abstractmultiple sclerosis ms immunemediated demyelinating degenerative disease unknown etiology inappropriate response tcells myelin antigens essential role pathophysiology ms clinical pathophysiological complications ms necessitate identification potential molecular targets understand pathogenic events ms since functions regulatory mechanisms long noncoding rnas lncrnas acting competing endogenous rnas cernas ms yet uncertain conducted bioinformatics analysis explain lncrnaassociated cerna axes clarify molecular regulatory mechanisms involved tcells responses ms two microarray datasets peripheral blood tcell subjects relapsingremitting ms matched controls containing data mirnas gse43590 mrnas lncrnas gse43591 downloaded gene expression omnibus database differentially expressed mirnas demirnas mrnas demrnas lncrnas delncrnas identified limma package r software proteinprotein interaction ppi network module developed using search tool retrieval interacting genes proteins string molecular complex detection mcode cytoscape plugin respectively using dianalncbase mirtarbase lncrnaassociated cerna axes constructed conducted pearson correlation analysis selected positive correlations among lncrnas mrnas cerna axes lastly demrnas pathway enrichment conducted enrichr tool cerna regulatory relationship among small nucleolar rna host gene 1 snhg1 hsamir1973p yod1 deubiquitinase yod1 zinc finger protein 101 znf101 downstream connected genes identified pathway enrichment analysis showed demrnas enriched protein processing endoplasmic reticulum herpes simplex virus 1 infection pathways knowledge first report possible role snhg1 hsamir1973p yod1 znf101 axes pathogenesis ms research remarks significance cernas prepares new perceptions discovering molecular mechanism mspmid34956196 pmcpmc8696673 doi103389 fimmu2021770679,1.0
salivary uric acid noninvasive wonder clinicians cureus 2021 nov 16 13 11 e19649 doi 107759 cureus19649 ecollection 2021 novabstractthis review summary modernday approach recent trend determination uric acid saliva humans use diagnosis clinicians uric acid end product obtained breakdown purine nucleotides important biomarker associated various conditions uric acid found various body fluids serum plasma urine can used important tool various diseases gout hyperuricemia conditions associated increased oxidative stress recently emergence studies utilized uric acid concentrations measured saliva studied association various diseases salivary uric acid can prove noninvasive method provide diagnosis serious illness raised uric acid level saliva can associated cancer human immunodeficiency virus hiv infection gout hypertension reduced level salivary uric acid hand can marker alzheimers disease progression multiple sclerosis impairment cognition online search databases including google scholar scopus pubmed web science searched articles published september 2021 based salivary uric acid analysis analyzed review uric acid essential biomarker antioxidant properties assessment salivary uric acid levels found essential conditions cancer metabolic syndrome neurological conditions psychiatric conditions human immunodeficiency virus gout monitoring treatment hyperuricemia although importance diagnosis therapeutic monitoring salivary uric acid analysis gained enough popularity due limitations saliva collection sample processing issues proper education standardization salivary uric acid analysis can used costeffective noninvasive tool getting clue antioxidant biomarker concentration saliva hence various diseases associated oxidative stresspmid34956769 pmcpmc8675576 doi107759 cureus19649,0.0
assessing causal relationship human blood metabolites five neurodegenerative diseases gwas summary statistics front neurosci 2021 dec 9 15680104 doi 103389 fnins2021680104 ecollection 2021abstractbackground neurodegenerative diseases ndds leading cause disability worldwide metabolic pathogenesis unclear genomewide association studies gwass offer unprecedented opportunity untangle relationship metabolites ndds methods leveraging twosample mendelian randomization mr approaches relying gwass summary statistics explore causal association 486 metabolites five ndds including alzheimers disease ad amyotrophic lateral sclerosis als frontotemporal dementia ftd parkinsons disease pd multiple sclerosis ms validated mr results extensive sensitive analyses including mrpresso mregger regression also performed linkage disequilibrium score regression ldsc colocalization analyses distinguish causal metabolitendd associations genetic correlation ld confounding shared causal genetic variants finally metabolic pathway analysis conducted identify potential metabolite pathways results detected 164 metabolites suggestively associated risk ndds particularly 2methoxyacetaminophen sulfate substantially affected als 0971 95cis 0961 0982 fdr 104e4 ftd 0924 95cis 0885 0964 fdr 0048 x11529 1604 95cis 1250 2059 fdr 0048 x13429 2284 95cis 1457 3581 fdr 0048 significantly impacted ftd associations confirmed weighted median maximum likelihood methods mrpresso mregger regression removing possibility pleiotropy also observed als ftd can alter metabolite levels including als ftd 2methoxyacetaminophen sulfate ldsc colocalization analyses showed none identified associations driven genetic correlation confounding ld common causal loci multiple metabolic pathways found involved ndds urea cycle p 0036 arginine biosynthesis p 0004 ad phenylalanine tyrosine tryptophan biosynthesis p 0046 als conclusion study reveals robust bidirectional causal associations servaral metabolites neurodegenerative diseases provides novel insight metabolic mechanism pathogenesis therapeutic strategies diseasespmid34955704 pmcpmc8695771 doi103389 fnins2021680104,0.0
overactive bladder symptoms within nervous system focus etiology front physiol 2021 dec 10 12747144 doi 103389 fphys2021747144 ecollection 2021abstractoveractive bladder oab common debilitating condition characterized urgency symptoms detrimental effects quality life survival exact etiology oab still enigmatic none therapeutic approaches seems curative oab generally regarded separate syndrome whereas clinic oab symptoms found numerous diseases nonurogenital systems particularly nervous system oab symptoms neurological diseases often poorly recognized inadequately treated review provided comprehensive overview recent findings related neurogenic oab symptoms relevant neurological diseases mainly divided seven kinds follows multiple sclerosis related neuroinflammatory disorders parkinsons diseases multiple system atrophy spinal cord injury dementia peripheral neuropathy others concurrently also summarized hypothetical reasonings available animal models elucidate underlying mechanism neurogenic oab symptoms review highlighted close association oab symptoms neurological diseases expanded current knowledge pathophysiological basis oab may increase awareness urological complaints neurological disorders inspire robust therapies better outcomespmid34955876 pmcpmc8703002 doi103389 fphys2021747144,0.0
multiple sclerosis masquerading post septorhinoplasty complication case report cureus 2021 nov 15 13 11 e19591 doi 107759 cureus19591 ecollection 2021 novabstractthis case report young woman successful septorhinoplasty procedure sustained repeated nasal trauma subsequent diagnosis multiple sclerosis ms large tertiary hospital riyadh saudi arabia 24yearold woman history childhood trauma presented difficulty breathing dissatisfaction nasal appearance successful uneventful septorhinoplasty required numerous hospital admissions due multiple episodes blunt nasal trauma culminating clear nasal discharge neurological symptoms including dizziness rightsided paresthesia difficulty walking cerebrospinal fluid csf leak ruled ct brain however magnetic resonance imaging mri brain spinal cord showed demyelinating areas brain cervical region spinal cord csf examination revealed presence oligoclonal bands neurologist confirmed diagnosis ms initiated treatment well tolerated patient remission mild paresthesia right hand despite repeated nasal trauma septorhinoplasty procedure excellent outcome conclusion repeated nasal trauma especially early postoperative period addition procedure failure may also point presence uncommon underlying neurological disorder hitherto undiagnosed therefore important open mind comes differential diagnosis unusual scenarios addition investigating recurrent nasal trauma extremely important keep mind rare neurological conditions especially younger patientspmid34956744 pmcpmc8675578 doi107759 cureus19591,1.0
leveraging visual outcome measures advance therapy development neuroimmunologic disorders neurol neuroimmunol neuroinflamm 2021 dec 26 9 2 e1126 doi 101212 nxi0000000000001126 print 2022 marabstractthe visual system offers unparalleled precision assessment neuroaxonal damage majority patients multiple sclerosis ms experiencing afferent efferent visual dysfunction outcome measures capturing deficits provide insight neuroaxonal injury even minimal disability ideal use clinical trials visual measures generally inexpensive accessible reproducible quantification visual acuity visual fields visual quality life electrophysiologic parameters allows assessment function whereas optical coherence tomography oct provides reliable measures structural integrity anterior afferent visual pathway technology oculomotor biometrics continues advance discrete measures fixation smooth pursuit saccadic eye movement abnormalities ready inclusion future trials ms progression visual outcomes allow tracking neuroaxonal injury aid distinguishing ms diseases neuromyelitis optica spectrum disorder nmosd myelin oligodendrocyte glycoprotein antibodyassociated diseases mogad oct also provided unique insights pathophysiology including identification foveal pitting nmosd possibly damage mller cells carry abundance aquaporin4 channels study designs costbenefit ratio favors visual outcomes expensive mri outcomes next frontier therapeutics focused remyelination neuroprotection visual outcomes likely take center stage international community collaborative committed vision scientists review international ms visual system consortium imsvisual outlines quality standards informatics framework needed routinely incorporate vision outcomes ms nmosd trialspmid34955459 doi101212 nxi0000000000001126,1.0
efficacy virtual reality exergaming improving balance patients multiple sclerosis systematic review metaanalysis front neurol 2021 dec 10 12773459 doi 103389 fneur2021773459 ecollection 2021abstractmultiple sclerosis ms one common causes neurological progressive disease can lead loss mobility walk impairment balance disturbance among several rehabilitative approaches proposed exergaming virtual reality vr studied recent years active video game therapy reduce boredom rehabilitation process increasing patient motivation providing direct feedback enabling dualtask training aim systematic review assess efficacy exergaming vr balance recovery patients ms pubmed scopus web science systematically searched inception may 14 2021 identify randomized controlled trials rcts presenting patients ms participants exergaming vr intervention conventional rehabilitation comparator balance assessment berg balance scale bbs outcome measure also performed metaanalysis mean difference bbs via randomeffects method 93 records systematic review included analyzed 7 rcts involving total 209 patients affected ms 97 patients performed exergaming vr 112 patients underwent conventional rehabilitation metaanalysis reported significant overall es 425 p 00001 showing subgroup analysis nonsignificant es 185 p 039 vr significant es 449 p 00001 exergames terms bbs improvement taken together findings suggested balance rehabilitation using exergames appears effective conventional rehabilitation patients affected mspmid34956054 pmcpmc8702427 doi103389 fneur2021773459,0.0
usefulness visual evoked potentials assessment pediatric multiple sclerosis eur j paediatr neurol 2021 dec 14 36130136 doi 101016 jejpn202112005 online ahead printabstractbackground evaluate significance visual evoked potentials vep early diagnosis optic neuritis detecting clinically silent lesions pediatric multiple sclerosis pedms study represents one largest series pedms evaluated characteristics vep pedms patientsmethods retrospective study 52 pedms patients aged 717 years vep analysis done patients first attack disease compared control subjects according patternreversal vep findingsresults mean age patients 1565 189 years male female ratio 16 308 36 692 patients relapsingremitting course disease discovered initial attack 18 346 patients 30 577 patients second attack pathological vep findings present 40 769 patients 22 423 pedms patients clinically silent lesions prolonged latency p100 waves pedms group statistically significant compared control subjects amplitude n1p1 showed correlation residual visual deficitconclusion results show common initial manifestation pedms serbian pedms population prolonged p100 latency main indicator vep objective fast accessible diagnostic method detecting clinical subclinical lesions thus vep deserves evaluation considered additional criterion pedms diagnosispmid34959110 doi101016 jejpn202112005,0.0
endothelial dysfunction pathological processes chronic liver disease aging abstractaging associated gradual changes liver structure physiological pathological functions hepatic cells including hepatocytes cholangiocytes kupffer cells hepatic stellate cells hscs liver sinusoidal endothelial cells lsecs lsecs specialized hepatic endothelial cells regulate liver homeostasis cells actively impact hepatic microenvironment fenestrations thin morphology allow substance exchange circulating blood liver tissue aging occurs lsecs reduction number size fenestrations referred pseudocapillarization along aging liver leads increased oxidative stress decreased availability nitric oxide decreased hepatic blood flow increased inflammatory cytokines lsecs vascular aging can also lead hepatic hypoxia hsc activation liver fibrosis review described basic structure lsecs effect lsecs hepatic inflammation fibrosis aging process briefly summarized changes hepatic microcirculation liver inflammation effect aging clearance function lsecs interactions lsecs immunity hepatocytes hepatic nonparenchymal cells therapeutic intervention liver diseases targeting lsecs vascular system since lsecs play important role development liver fibrosis changes lsec phenotype occur early stage liver fibrosis study lsecs fibrotic liver valuable detection early liver fibrosis early intervention fibrotic response,0.0
aerobic capacity fatigue relationship persons multiple sclerosis reproducible pooled analysis two randomized controlled trials abstractbackgroundfatigue one frequent symptoms persons multiple sclerosis pwms limited treatment options aerobic capacity endurance training discussed relevant factors improve fatigue however last decades results equivocal secondary analysis two pooled parallel group rcts three weeks endurance training high intensity interval training hiit moderate continuous training mct pwms aimed reproduce reported associations aerobic capacity fatigue crosssectional interventional level analysis aimed ii investigate intervention effects fatigue severely fatigued subgroup iii analyze differences changes fatigue peak oxygen uptake vo2peak responders nonrespondersmethodsboth rcts conducted inpatient rehabilitation clinic valens switzerland original primary outcomes cognitive function rct1 change proportion circulating regulatory tcells rct2 pwms n131 relapsingremitting secondary progressive ms phenotype expanded disability status scale score 1 65 eligible two studies participants exercised 3 5 times per week cycle ergometers intensities 65 70 maximum heart rate hrmax 30min mct groups three times per week five 90 180s intervals intensities 85 100 hrmax 90s rest intervals hiit groups main outcome measures present secondary analysis vo2peak measured cardiopulmonary exercise test fatigue scale motor cognitive functions fsmc assessed start end inpatient rehabilitationresultsbaseline correlations reveal significant association vo2peak fsmc significant improvements fatigue hiit mct overall sample subsample severely fatigued pwms significant differences fatigue changes vo2peakresponders nonrespondersconclusionsour analyses confirm aerobic capacity fatigue relationship crosssectional experimental level even analyzing subgroups benefit according proposed hypotheses,0.0
patient perspectives patientreported outcomes multiple sclerosis treatment trajectories qualitative study abstractbackground interest patientreported outcomes growing multiple sclerosis research clinical care recent years situation reflects need developing testing integrating measures adequately capture patientsnull perspectives symptoms functional capacity health status healthrelated quality life however patient perspective relevance content use patientreported outcomes yet investigated hence study aims investigate perspectives people multiple sclerosis value patientreported outcomes clinical encounters important aspects living multiple sclerosis reflected reports possible opportunities barriers integrating data clinical caremethods qualitative study conducted capture patient perspectives danish population people multiple sclerosis initially two focus group interviews conducted total 11 participants explore perspectives patientreported outcomes related prospects barriers subsequently nine individual interviews conducted investigate identified aspects opportunities barriers use patientreported outcomes clinical care treatmentresults general informants motivated report patientreported outcomes believed reports relevant clinical encounters well potential promote patient involvement focusing current challenges others disease however differences perceived need reporting patientreported outcomes detected regarding stage multiple sclerosis care trajectory relation disease phenotypes terms domains incorporated patientreported outcomes total 28 identified informants including neurological symptoms cognitive impairments mental health wellbeing selfcare activities social challenges several factors integrating patientreported outcomes clinical care emerged important particular related timing frequency reporting patient reported outcomes considerations cognitive impairments need individualized approaches patientreported outcomes need active use reports adjustment treatment approaches clinical encountersconclusion perspective people multiple sclerosis patientreported outcomes hold important potential enhanced patient involvement leading multifaceted agenda clinical consultations however patientreported outcomes need comprehensive encompass broad range measures regarding neurological symptoms cognitive impairments mental health wellbeing selfcare activities social challenges adequately capture support needs people multiple sclerosis clinical encounters important address barriers integration patientreported outcomes clinical care aim preventing misuse future studies focus synergy perspectives patients clinicians understand integration patientreported outcomes clinical care can succeed,0.0
chemokine cxcl1 potential marker disease activity systemic lupus erythematosus abstractobjectivesthe chemokine cxcl1 known growthrelated oncogene gro potent chemoattractant regulator neutrophils purpose study evaluate regulatory response cxcl1 serum patients systemic lupus erythematosus sle active stage disease assess whether implicated pathogenesis inflammatory process lupusmethodscxcl1 serum concentrations examined 90 sle patients 56 autoimmune diseases oads patients 100 healthy controls using enzymelinked immunosorbent methodologyresultssle patients exhibited significant increases serum cxcl1 concentrations 149286 73547288734 pg ml compared oads patients 15588 107736678 pg ml healthy controls 1358 8463722 pg ml p 0001 moreover level cxcl1 decreased level antidsdna igg decreased treatment antidsdnapositive sle patients antidsdnanegative sle patients additionly serum cxcl1 concentrations related different disease activity levels sle lupus nephritis ln high avidity igg anas ha igg anas p 005 furthermore cxcl1 serum concentrations significantly correlated sle disease activity index sledai score relative avidity index rai ha igg anas levels antidsdna igg crp esr albumin c3 c4additionally statistical analysis revealed positivity igg ana p 0001 presence ha igg anas p 0001 logarithmic level antidsdna igg p 0021 significantly associated logarithmic level cxcl1 standard partial regression coefficients 95 ci 2371 17343009 1231 0521937 0409 00620755 respectively finally using cutoff points 118217 pg ml 150031 pg ml serum cxcl1 levels similar sensitivity 76 specificity 100 75 diagnosis active sle ln respectivelyconclusionsserum cxcl13 concentrations might represent potential marker disease activity systemic lupus erythematosus,0.0
citrullinated myelin induces microglial tnf inhibits endogenous repair cuprizone model demyelination background microglia primary phagocytes central nervous system responsible removing damaged myelin following demyelination previous investigations exploring consequences myelin phagocytosis microglial activation overlooked biochemical modifications present myelin debris modifications including citrullination increased within inflammatory environment multiple sclerosis lesionsmethodsmouse cortical myelin isolated ultracentrifugation citrullinated ex vivo incubation calciumdependent peptidyl arginine deiminase pad2 demyelination induced 6 weeks cuprizone 03 treatment spontaneous repair initiated reversion normal chow citrullinated unmodified myelin injected primary motor cortex cingulum bundle time reversion normal chow consequent impact remyelination assessed measuring surface area myelin basic proteinpositive fibers cortex 3 weeks later microglial responses myelin characterized measuring cytokine release assessing flow cytometric markers microglial activation rnaseq profiling transcriptional changesresultscitrullinated myelin induced unique microglial response marked increased tumor necrosis factor tnf production vitro vivo response induced unmodified myelin injection citrullinated myelin unmodified myelin cortex cuprizonedemyelinated mice significantly inhibited spontaneous remyelination antibodymediated neutralization tnf blocked effect restored remyelination normal levelsconclusionsthese findings highlight role posttranslation modifications citrullination determination microglial activation response myelin demyelination inhibition endogenous repair induced citrullinated myelin reversal effect neutralization tnf may implications therapeutic approaches patients inflammatory demyelinating disorders,1.0
methodological approaches conducting followup research clinical trial participants scoping review expert interviews background evidencebased establishment implementation best principles laws ordinances regulate clinical research depend consultation involvement trial participants yet guidance methodological approaches obtain trial participants perspectives currently missing scoping review therefore aimed identifying describing evaluating research approaches obtain trial participants feedback views experiencesmethodswe searched electronic databases medline psycinfo via ovid web science core collection clinical trials included involved adult participants conducted selected highincome countries published peerreviewed journals 1985 2018 addition 29 expert interviews conducted march may 2019resultsout 5994 identified records 23 articles included review twelve studies used qualitative approach 10 quantitative one study used mixedmethod design 75 work conducted usa uk scoping review expert interviews highlighted recruitment participants generally done direct contact principal investigators study nurses searches deidentified patient databases authors used surveys interviews focus group discussions tools used either based existing validated ones developed verified de novo support experts patient representativesconclusionsto knowledge first methodological literature review approaches researching experiences clinical trial participants findings triangulated expert interviews covering range indications trial phases study settings demonstrates clinical trial participant perspectives experience heavily underresearched casts doubt overall robustness available insight trial participants views experiences results demonstrate methodology studying participant opinion perception experience adapted measure interest conform study population using valid patient experience data basis evaluate existing legal regulatory human subject research frameworks appropriateness patient perspective evaluation will critical empower research participants,0.0
myelinassociated glycoprotein activation triggers glutamate uptake oligodendrocytes vitro contributes ameliorate glutamatemediated toxicity vivo biochim biophys acta mol basis dis 2021 dec 23166324 doi 101016 jbbadis2021166324 online ahead printabstractbackground myelinassociated glycoprotein mag key molecule involved nurturing effect myelin ensheathed axons mag also inhibits axon outgrowth injury preclinical stroke models administration functionblocking antimag monoclonal antibody mab aimed improve axon regeneration demonstrated reduced lesion volumes rapid clinical improvement suggesting mechanism immediate neuroprotection rather enhanced axon regeneration addition reported antibodymediated crosslinking mag can protect oligodendrocytes ols glutamate glu overload unknown mechanismspurpose unravel molecular mechanisms underlying protective effect antimag therapy focus neuroprotection glu toxicityresults mag activation via antibody crosslinking triggered clearance extracellular glu uptake ols via high affinity excitatory amino acid transporters resulted protection ols also nearby neurons mag activation led pkcdependent activation factor nrf2 nuclearerythroid related factor2 leading antioxidant responses including increased mrna expression metabolic enzymes glutathione biosynthetic pathway regulatory chain cystine glu antiporter system xc increasing reduced glutathione gsh main antioxidant cells efficacy early antimag mab administration demonstrated preclinical model excitotoxicity induced intrastriatal glu administration extended model experimental autoimmune encephalitis showing axonal damage secondary demyelinationconclusions mag activation triggers glu uptake ols conditions glu overload induces robust protective antioxidant responsepmid34954343 doi101016 jbbadis2021166324,1.0
sarcopenia patients multiple sclerosis abstractbackground multiple sclerosis ms autoimmune neurodegenerative disease central nervous system sarcopenia characterized loss physical performance poor outcomes recently become focus research however relationship sarcopenia ms yet investigated study aims determine prevalence sarcopenia ms patients investigate factors associated sarcopeniamethods one hundred one ms patients can walk without assistance 55 healthy controls included handgrip strength hgs gait speed tests applied participants additionally anterior thigh muscle thickness anterior tmt skeletal muscle mass index ssmi estimated ultrasound bioelectrical impedance analysis bia respectively according tests ms patients grouped either sarcopenic nonsarcopenic groups compared using clinical laboratory data handgrip strength performance test modified fatigue impact scale mfis godin leisuretime exercise questionnaire glteq results hgs gait speed fat free mass ffm smmi anterior tmt sonographic thigh adjustment ratio star values patients ms significantly lower healthy controls sexes female p0001 p0001 p0010 p0049 p0001 p0101 respectively male p0001 compared healthy controls ms patients significantly lower glteq score p0001 mfis score p0001 higher according star hgs gait speed sarcopenia diagnosed 12 1764 female 7 2121 male patients ms wholebody sarcopenia diagnosed 11 109 patients bia hgs gait speed ffm anterior tmt star values sarcopenic ms patients significantly lower nonsarcopenic females p0001 p0001 p0004 p0001 p0001 respectively males p0001 p0001 p0011 p0003 p0001 respectively mfis score significantly higher sarcopenic patients nonsarcopenic females p0001 males p0036 physical fatigue subscale significantly higher physical fatigue score negatively correlated glteq ms patients r0276 p0005 positively correlated expanded disability status scale r0409 p0001 conclusion detected approximately onefifth ms patients sarcopenia regional sarcopenia prevalent whole body sarcopenia found high degree fatigue lack exercise sarcopenic ms patients,0.0
validity reliability modified tardieu scale spasticity outcome measure upper limbs adults neurological conditions systematic review narrative analysis bmj open 2021 dec 24 11 12 e050711 doi 101136 bmjopen2021050711abstractpurpose evaluate published evidence modified tardieu scale mts tool assess spasticity upper limbs adults neurological conditionsdata sources systematic search six electronic databases pubmed medline cinahl embase cochrane library web science physiotherapy evidence database inception 31 december 2020 search strategy developed using key elements research question population intervention action outcomestudy eligibility criteria inclusion criteria 1 adult participants neurological conditions 2 upper limb muscles joints tested elements 3 studies testing mts 4 reliability validity reportedexclusion criteria 1 nonenglish articles 2 nonempirical articles 3 studies testing tardieu scalestudy appraisal evidence quality evaluated using us national heart lung blood institute quality assessment tool observational cohort crosssectional studiesresults six reliability studies met inclusion criteria overall articles reported goodtoexcellent levels interrater intrarater testretest reliability however limitations study design weaknesses statistical misuses reporting biases undermine confidence reported conclusions validity mts also remained questionable based results one studyconclusions implications review find sufficient evidence either support reject use mts assessing spasticity upper limbs adults neurological conditions despite paucity research evidence mts may still remain clinically useful tool measure motor aspect spasticity future research benefit focus test standardisation wider field require development consensual definition spasticitypmid34952873 doi101136 bmjopen2021050711,0.0
human oligodendrocyte myelination potential relation age differentiation ann neurol 2021 dec 24 doi 101002 ana26288 online ahead printabstractobjective myelin regeneration human central nervous system relies progenitor cells within tissue parenchyma possible contribution previously myelinating oligodendrocytes multiple sclerosis demyelinating disorder variables affecting remyelination efficiency include age severity initial injury progenitor cell properties aim investigate effects age differentiation myelination potential human oligodendrocyte lineage cellsmethods derived viable primary oligodendrocyte lineage cells surgical resections pediatric adult brain tissue ensheathment capacity using nanofiber assays transcriptomic profiles rna sequencing compared a2b5+ antibodyselected progenitors mature oligodendrocytes nonselected cells results demonstrate pediatric progenitor mature cells ensheathed nanofibers robustly adult progenitor mature cells respectively within age groups percentage fibers ensheathed ensheathment length per fiber greater a2b5+ progenitors gene expression oligodendrocyte progenitor markers pdgfra ptprz1 higher a2b5+ vs a2b5 cells pediatric a2b5+ vs adult a2b5+ cells p38 map kinases actin cytoskeletonassociated pathways upregulated pediatric cells shown regulate ol process outgrowth significant upregulation cell senescence genes detected pediatric samples reflect role development increased susceptibility pediatric oligodendrocytes activating cell death responses stressinterpretation findings identify specific biological pathways relevant myelination differentially enriched human pediatric adult oligodendrocyte lineage cells suggest potential targets remyelination enhancing therapies article protected copyright rights reservedpmid34952986 doi101002 ana26288,1.0
association deprivation access disease modifying therapies multiple sclerosis england wide communitybased study uk ms register abstractbackgrounddeprivation can impact access health interventions publicly funded health systems cost dominant barrier study examined whether deprivation affected access disease modifying therapies dmts multiple sclerosis ms methodsall english adults uk ms register relapsing remitting ms diagnosed 2010 2017 age 29 years included deprivation measured using postcode based 2015 english index multiple deprivation imd divided quintilesresultsa total 1449 participants eligible 531 1449 366 received dmts participants lived deprived areas based imd scores significantly less likely receive dmts odds ratio069 95 confidence interval049 098 barriers housing services contributed disparity nagelkerke r2 value models showed 2 variation accessing dmts dependent deprivationconclusionsdeprivation measured imd negatively influences access dmts england findings also suggest lack access local ms dmt clinics deprived areas may contribute disparity,0.0
hippo signaling pathway leukemia function interaction carcinogenesis abstractcancer can considered communication disease within cells nevertheless effective therapy condition disease typically identified late stage chemotherapy radiation moleculartargeted treatment typically ineffective cancer cells better grasp processes carcinogenesis aggressiveness metastasis treatment resistance detection illness earlier stage obtaining better therapeutic response will made possible researchers discovered cancerous mutations mainly affect signaling pathways hippo pathway one main signaling pathways cell unique ability cause cancer order treat cancer complete understanding hippo signaling system will required hand interaction pathways like wnt tgf ampk notch jnk mtor ras map kinase pathways can contribute carcinogenesis phosphorylation oncogene yap taz lead leukemogenesis process regulated via signaling pathways review article aimed shed light hippo pathway interacts cellular signaling networks functions leukemia,0.0
patient carer staff perceptions robotics motor rehabilitation systematic review qualitative metasynthesis background recent years robotic rehabilitation devices often used motor training however date systematic reviews qualitative studies exploring enduser experiences robotic devices motor rehabilitation published aim study review endusers patients carers healthcare professionals experiences robotic devices motor rehabilitation conducting systematic review thematic metasynthesis qualitative studies concerning users experiences robotic devicesmethodsqualitative studies mixedmethods studies qualitative element eligible inclusion nine electronic databases searched inception august 2020 supplemented internet searches forward backward citation tracking included studies review articles data synthesised thematically following thomas harden approach casp qualitative checklist used assess quality included studies reviewresultsthe search strategy identified total 13 556 citations removing duplicates excluding citations based title abstract full text screening 30 studies included studies considered acceptable quality developed six analytical themes logistic barriers technological challenges appeal engagement supportive interactions relationships benefits physical psychological social function ing expanding sustaining therapeutic optionsconclusionsdespite experiencing technological logistic challenges participants found robotic devices acceptable useful beneficial physically psychologically socially well fun interesting supportive relationships significant others positive therapeutic relationships healthcare staff considered foundation successful rehabilitation recovery,0.0
diseasemodifying drugs multiple sclerosis subsequent health service use abstractobjectivewe assessed relationship multiple sclerosis ms diseasemodifying drugs dmds healthcare usemethodspersons ms aged 18 years identified using linked populationbased health administrative data four canadian provinces followed recent first ms demyelinating event 1 january 1996 earliest death emigration study end 31 december 2017 31 march 2018 prescription records captured dmd exposure examined dmd generation firstgeneration injectables secondgeneration orals infusions individual dmd associations subsequent allcause hospitalizations physician visits examined using proportional means model negative binomial regressionresultsof 35 894 ms cases 72 female mean followup 120 years personyears dmd exposure first secondgeneration dmd 63 290 54 605 8685 respectively dmd firstgeneration dmd exposure versus nonexposure associated 24 lower hazard hospitalization adjusted hazard ratio ahr 076 95 confidence intervals cis 071082 rising 29 secondgeneration dmds ahr 071 95 ci 058088 ranged 18 teriflunomide ahr 082 95 ci 067100 44 fingolimod ahr 056 95 ci 036087 contrast dmd exposure generally associated substantial differences physician visitsconclusionfindings provide realworld evidence beneficial relationship dmd exposure hospitalizations,1.0
trigeminal neuralgia associated solitary pontine lesion case report neurohospitalist 2022 jan 12 1 143146 doi 101177 19418744211027754 epub 2021 aug 3abstracttrigeminal neuralgia associated brainstem lesions currently considered rare condition patients reported far literature tohyama colleagues recently proposed nosological entity trigeminal neuralgia associated solitary pontine lesion trying categorize new clinical syndrome based description trigeminal neuralgia associated solitary pontine lesion patients identical clinical presentation compared patients trigeminal neuralgia solitary pontine lesion nature pontine lesion attributed several etiologies including ischemia demyelination previous pontine viral neuritis patients putative demyelinating lesion definite diagnosis multiple sclerosis made due lack dissemination space little known relation cerebrospinal fluid characteristics population patients present case 42yearold man suffering trigeminal neuralgia associated solitary pontine lesion possible demyelinating etiology patient herein described atypical trigeminal neuralgia associated single pontine lesion mri characteristics lesion along presence oligoclonal bands cerebrospinal fluid suggested demyelinating etiology trigeminal neuralgia associated solitary pontine lesion may categorized possible manifestation solitary sclerosis future research need reveal features can predict risk conversion clinically defined multiple sclerosis treatments modify riskpmid34950403 pmcpmc8689539 doi101177 19418744211027754,1.0
long noncoding rnas novel offenders guardians multiple sclerosis scoping review front immunol 2021 dec 7 12774002 doi 103389 fimmu2021774002 ecollection 2021abstractmultiple sclerosis ms chronic inflammatory demyelinating disease central nervous system one common neurodegenerative diseases worldwide ms results serious neurological dysfunctions disability disturbances coding noncoding genes key components leading neurodegeneration along environmental factors long noncoding rnas lncrnas long molecules cells take part regulation gene expression several studies confirmed role lncrnas neurodegenerative diseases ms current study performed systematic analysis role lncrnas disorder total 53 studies recognized eligible systematic review listed lncrnas 52 lncrnas upregulated 37 lncrnas downregulated 11 lncrnas significant expression difference ms patients compared controls also summarized mechanisms lncrna functions ms emerging role lncrnas neurodegenerative diseases suggests dysregulation trigger neuronal death via still unexplored rnabased regulatory mechanisms evaluation diagnostic significance therapeutic potential help design novel treatments mspmid34950142 pmcpmc8688805 doi103389 fimmu2021774002,1.0
identification clinical validation key extracellular proteins potential biomarkers relapsingremitting multiple sclerosis front immunol 2021 dec 7 12753929 doi 103389 fimmu2021753929 ecollection 2021abstractbackground multiple sclerosis ms demyelinating disease central nervous system cns mediated autoimmunity objective clinical indicators available diagnosis prognosis ms extracellular proteins glycosylated likely enter body fluid serve potential biomarkers work will contribute indepth study functions extracellular proteins discovery disease biomarkersmethods ms expression profiling data human brain downloaded gene expression omnibus geo extracellular proteindifferentially expressed genes epdegs screened protein annotation databases go kegg used analyze function pathway epdegs string cytoscape mcode cytohubba used construct proteinprotein interaction ppi network screen key epdegs key epdegs levels detected csf ms patients roc curve survival analysis used evaluate diagnostic prognostic ability key epdegsresults screened 133 epdegs degs epdegs enriched collagencontaining extracellular matrix signaling receptor activator activity immunerelated pathways pi3kakt signaling pathway ppi network epdegs 85 nodes 185 edges identified 4 key extracellular proteins il17a il2 cd44 igf1 16 extracellular proteins interacted il17a clinically verified il17a levels decreased del1 resolvind1 levels increased diagnostic accuracy del1 auc 0947 superior igg auc 0740 sensitivity 824 specificity 100 high del1 levels significantly associated better relapsefree progressionfree survivalconclusion il17a il2 cd44 igf1 may key extracellular proteins pathogenesis ms il17a del1 resolvind1 may coregulate development ms del1 potential biomarker ms used bioinformatics methods explore biomarkers ms validated results clinical samples study provides theoretical experimental basis revealing pathogenesis ms improving diagnosis prognosis mspmid34950135 pmcpmc8688859 doi103389 fimmu2021753929,1.0
fatigue physical disability selfefficacy predictors acceptance illness healthrelated quality life patients multiple sclerosis int j environ res public health 2021 dec 15 18 24 13237 doi 103390 ijerph182413237abstractmultiple sclerosis ms chronic progressive demyelinating disease central nervous system leads permanent disability many neurological symptoms making everyday functioning difficult predictors acceptance illness healthrelated quality life people ms include degree disability neurological symptoms psychosocial factors personal resources aim study determine relationships among disability fatigue selfefficacy acceptance illness quality life study group consisted 137 people diagnosed multiple sclerosis73 women 64 men edss gnds lses ais msis29 used present study results show tested variables significantly correlated disability fatigue significant predictors physical psychological aspects patients quality life selfefficacy significant predictor acceptance illness psychological aspect patients quality life based current research study can concluded factors biomedical nature explain aspects struggling disease rather psychological resourcespmid34948845 doi103390 ijerph182413237,1.0
realworld comparative costeffectiveness analysis different classes diseasemodifying therapies relapsingremitting multiple sclerosis saudi arabia int j environ res public health 2021 dec 16 18 24 13261 doi 103390 ijerph182413261abstractthe fact multiple sclerosis ms incurable necessitates lifelong care makes one burdensome illnesses aim study compare costeffectiveness orally administered medications eg fingolimod dimethyl fumarate teriflunomide interferon ifn based therapy monoclonal antibodies mabs eg natalizumab rituximab management relapsingremitting multiple sclerosis rrms saudi arabia using realworld data retrospective cohort study patients rrms aged 18 years without chronic health conditions nonmissing data least 12 months recruited electronic health records universityaffiliated tertiary care center multiple logistic regressions controlling age sex duration therapy conducted examine odds disability progression clinical relapse mri lesions composite outcome eg relapse lesion development mri disability progression number patients met inclusion criteria included analysis 146 patients female 7051 young eg 35 years age 40 patients orally administered agents eg dimethyl fumarate teriflunomide fingolimod 66 patients ifnbased therapy eg rebif 40 patients monoclonal antibodies eg rituximab natalizumab patients mabs lower odds composite outcome 017 95 ci 00680428 use orally administered agents dominant eg effective less costly average annual cost savings usd 433665 95 ci 520789390332 811 higher rate effectiveness 95 ci 14811807 compared rebif regard use mabs comparison rebif mabs associated higher cost better rate effectiveness average additional annual cost usd 138154 95 ci 42131362106 4311 higher rate effectiveness 95 ci 30386115 compared rebif addition use mabs associated higher cost better rate effectiveness average additional annual cost usd 571788 95 ci 497075827266 35 higher rate effectiveness 95 ci 1004250 compared orally administered agents use mabs management rrms among young patient population shown effective therapy comparison ifnbased therapy eg rebif orally administered agents higher cost orally administered agents resulted better outcomes lower costs comparison ifnbased therapy future studies examine costeffectiveness different diseasemodifying therapies management rrms using robust study designspmid34948876 doi103390 ijerph182413261,0.0
exercise training multiple sclerosis narrative review history benefits safety guidelines promotion int j environ res public health 2021 dec 16 18 24 13245 doi 103390 ijerph182413245abstractbackground significant advances medical treatment management multiple sclerosis pathogenesis relapse disease progression past 30 years advancements symptomatic treatment multiple sclerosis including management secondary multiple sclerosis expressions walking cognitive dysfunction fatigue depression scientific evidence expert opinion suggest exercise may single effective nonpharmacological symptomatic treatment multiple sclerosis article presents historical context exercise training within multidisciplinary management multiple sclerosis guide neurologists healthcare providers recommended prescription exercise practical theoretical methods overcome barriers exercisemethod undertook critical search historical current literature regarding exercise multiple sclerosis viewpoint exercise promotion neurologists multidisciplinary care teamresults highlight everstrengthening body research indicating exercise safe effective improving symptoms multiple sclerosis exercise training may necessary reducing disease progressionconclusion seek encourage neurologists specialists multidisciplinary healthcare teams prescribe promote exercise diagnosis across stages disease trajectory using prescriptive guidelines part comprehensive ms care available tools include clinical education dispel historical myths related exercise multiple sclerosis clinical exercise guidelines behaviour change theory overcome patients barriers exercisepmid34948854 doi103390 ijerph182413245,1.0
human gut microbiota health selected cancers int j mol sci 2021 dec 14 22 24 13440 doi 103390 ijms222413440abstractthe majority epithelial surfaces body digestive tract respiratory urogenital systems colonized vast number bacteria archaea fungi protozoans viruses microbiota particularly intestines play important beneficial role digestion metabolism synthesis vitamins metabolites stimulate cytokine production human host used potential pathogens composition microbiota influenced several internal external factors including diet age disease lifestyle changes called dysbiosis may involved development various conditions metabolic diseases including metabolic syndrome type 2 diabetes mellitus hashimotos thyroidis graves disease can also play role nervous system disturbances multiple sclerosis alzheimers disease parkinsons disease depression association also found gut microbiota dysbiosis cancer health closely associated state microbiota homeostasis aim review describe associations human gut microbiota cancer examine potential role gut microbiota anticancer therapypmid34948234 doi103390 ijms222413440,0.0
extended dosing monoclonal antibodies multiple sclerosis mult scler 2021 dec 2413524585211065711 doi 101177 13524585211065711 online ahead printabstractover past two decades treatment options patients multiple sclerosis ms increased exponentially current therapeutic landscape evidence ms disease activity within reach many patients minimizing risks complications improving treatment convenience decreasing health care costs goals yet reached one way optimize ms therapy implement personalized extended interval dosing monoclonal antibodies suitable candidates personalized dosing therapeutic drug monitoring extended interval dosing increasing number studies performed underway reporting altered dosing intervals anti41integrin treatment natalizumab anticd20 treatment ocrelizumab rituximab ofatumumab ms review current available evidence regarding personalized extended interval dosing monoclonal antibodies ms discussed recommendations future research clinical practicepmid34949134 doi101177 13524585211065711,0.0
evidence animalassisted therapy neurological diseases adults systematic review int j environ res public health 2021 dec 7 18 24 12882 doi 103390 ijerph182412882abstractbackground recent years possibility intervening humans animalassisted therapy aat growing due numerous physical psychological social benefits provided humanity enabling maintain improve quality life exist different animals therapy can performed purpose systematic review will focus effects aat several neurological diseasesmethods search clinical trials carried pubmed scielo embase pedro databases selection articles made according different inclusion exclusion criteria incorporating approached neurological diseases reviewedresults twentyfive clinical trials identified seventeen finally included review results indicate animalassisted therapy aat different neurological diseases many benefits several areas example motor physical ability well mental behavioural healthconclusions systematic review provides occupational therapy practitioners evidence use activity based animalassisted therapy novel field intervention can complement therapies obtain benefits different populationspmid34948491 doi103390 ijerph182412882,0.0
natalizumab rebound multiple sclerosis neurohospitalist 2022 jan 12 1 197198 doi 101177 19418744211031360 epub 2021 jul 7no abstractpmid34950414 pmcpmc8689555 doi101177 19418744211031360,0.0
whole fractionated human platelet lysate biomaterialsbased biotherapy induces strong neuroprotection experimental models amyotrophic lateral sclerosis biomaterials 2021 dec 4 280121311 doi 101016 jbiomaterials2021121311 online ahead printabstractamyotrophic lateral sclerosis als devastating neurodegenerative disease motor neurons leading death within 3 years without curative treatment neurotrophic growth factors ntfs pivotal cell survival reason lack patient efficacy single recombinant ntf brain infusion likely due synergistic neuroprotective action multiple ntfs diverse set signaling pathways fractionated protein size 50 30 10 3 kda heattreated human platelet lysate hhpl preparations adapted use brain tissue aim demonstrating therapeutic value als models elucidation mechanisms action neuronal culture fractions induced aktdependent neuroprotection well strong antiapoptotic antiferroptotic action 3 kda fraction antiferroptotic properties shown gpx4 dependent highlighting role platelet elements associated ntfs sod1g86r mouse model lifespan strongly increased intracerebroventricular delivery hhpl intranasal administration 3 kda fraction results suggest platelet lysate biomaterials neuroprotective als studies now validate theragnostic biomarker antiferroptotic action clinical developmentpmid34952382 doi101016 jbiomaterials2021121311,1.0
s100b protein therapeutic target multiple sclerosis s100b inhibitor arundic acid protects chronic experimental autoimmune encephalomyelitis int j mol sci 2021 dec 17 22 24 13558 doi 103390 ijms222413558abstracts100b astrocytic protein behaving high concentration damageassociated molecular pattern molecule direct correlation increased amount s100b inflammatory processes demonstrated particular inhibitor s100b activity pentamidine shown ameliorate clinical scores neuropathologicbiomolecular parameters relapsingremitting experimental autoimmune encephalomyelitis mouse model multiple sclerosis study investigates effect arundic acid aa known inhibitor astrocytic s100b synthesis chronic experimental autoimmune encephalomyelitis another mouse model multiple sclerosis usually studied daily evaluation clinical scores neuropathologicmolecular analysis performed spinal cord observed aatreated group showed lower severity compared vehicletreated mice particularly early phase disease onset also observed significant reduction astrocytosis demyelination immune infiltrates proinflammatory cytokines expression enzymatic oxidative reactivity aatreated group overall results reinforce involvement s100b development animal models multiple sclerosis propose aa targeting s100b protein focused potential drug considered multiple sclerosis treatmentpmid34948360 doi103390 ijms222413558,1.0
results 24month controlled prospective study relapsing multiple sclerosis patients risk progressive multifocal encephalopathy switched prolonged use natalizumab teriflunomide mult scler j exp transl clin 2021 dec 16 7 4 20552173211066588 doi 101177 20552173211066588 ecollection 2021 octabstractbackground natalizumab ntz highly effective disease modifying treatment relapsing multiple sclerosis rms increases risk progressive multifocal leukoencephalopathy pml patients serum anti john cunningham virus jcv antibodiesobjective assess safety efficacy rapid transition ntz teriflunomide tfm rms patientsmethods clinically stable ntztreated antijcv antibody positive rms patients switched tfm 28 7 days last dose ntz primary endpoint proportion relapse free patients 24 monthsresults median iqr age 55 enrolled patients 47 407 563 years 76 female median iqr number prior ntz treatments 34 18 64 annualized relapse rate arr 007 77 patients relapse free 24 months mean time first gad + lesion 196 months new enlarging t2 lesion 192 months mean time 3 month sustained disability worsening sdw 22 months proportion free 3month sdw 087 cases pmlconclusions washoutfree transition ntz tfm efficacious safe strategy patients risk developing pmlclinicaltrialsgov identifier nct01970410pmid34950502 pmcpmc8689625 doi101177 20552173211066588,0.0
developing clinicalenvironmentalgenotypic prognostic index relapsingonset multiple sclerosis clinically isolated syndrome brain commun 2021 dec 4 3 4 fcab288 doi 101093 braincomms fcab288 ecollection 2021abstractour inability reliably predict disease outcomes multiple sclerosis remains issue clinicians clinical trialists study aims create available clinical genetic environmental factors clinicalenvironmentalgenotypic prognostic index predict probability new relapses disability worsening analyses cohort included prospectively assessed multiple sclerosis cases n 253 2858 repeated observations measured 10 years n 219 diagnosed relapsingonset n 34 remained clinically isolated syndrome 10thyear review genotype data available 199 genetic variants associated multiple sclerosis risk penalized cox regression models used select potential genetic variants predict risk relapses worsening disability multivariable cox regression models backward elimination used construct clinicalenvironmental genetic clinicalenvironmentalgenotypic prognostic index respectively robust timecourse predictions obtained landmarking validate models weibull calibration models used chisquare statistics harrells cindex pseudor 2 used compare models predictive performance diagnosis evaluated using kullbackleibler brier dynamic prediction error reduction curves combined index clinicalenvironmentalgenotypic predicted quadratic timedynamic disease course terms worsening hr 274 ci 200376 pseudor 2064 cindex 076 relapses hr 216 ci 174268 pseudor 2 091 cindex 085 hr 332 ci 188586 pseudor 2 072 cindex 077 kullbackleibler brier curves suggested shortterm prognosis 5 years diagnosis clinicalenvironmental components disease relevant whereas genetic components reduced prediction errors longterm 5 years diagnosis combined components performed slightly better individual ones although prognostic sensitivities largely modulated clinicalenvironmental components created clinicalenvironmentalgenotypic prognostic index using relevant clinical environmental genetic predictors obtained robust dynamic predictions probability developing new relapses worsening symptoms multiple sclerosis prognostic index provides reliable information relevant longterm prognostication may used selection criterion risk stratification tool clinical trials work investigate component interactions required validate index independent data setspmid34950873 pmcpmc8691056 doi101093 braincomms fcab288,0.0
risk cardiovascular adverse events associated sphingosine1phosphate receptor modulators patients multiple sclerosis insights pooled analysis 15 randomised controlled trials front immunol 2021 dec 7 12795574 doi 103389 fimmu2021795574 ecollection 2021abstractbackground agents engaging sphongosine1phospate receptors s1prs will cardiovascular effect study aimed elucidate risk cardiovascular adverse events aes patients multiple sclerosis ms treated s1pr modulators s1prms methods systematically searched pubmed embase cochrane library databases randomised controlled trials rcts published january 5 2021 relative risks rrs 95 confidence intervals cis calculated using randomeffects model sensitivity analyses metaregression performedresults seventeen rcts 12 fingolimod 3 ozanimod 2 siponimod involving 13 295 patients included compared control treatment s1prms significantly increased risk cardiovascular aes rr 221 95 ci 158310 i2 756 notably highrisk cardiovascular aes associated s1prms primarily bradyarrhythmia rr 292 95 ci 191446 i2 308 hypertension rr 200 95 ci 149267 i2 565 subgroup analysis results consistent primary outcomes except ozanimod associated higher risk hypertension rr 176 95 ci 110282 i2 00 siponimod associated higher risk bradyarrhythmia rr 275 95 ci 175431 i2 00 significant intersubgroup differences observed pinteraction 005 conclusions s1prm use increased risk cardiovascular aes 121 times patients ms increased risks bradyarrhythmia hypertension 292 200fold respectively findings can help clinicians assess risk cardiovascular aes patients treated s1prmssystematic review registration prospero id crd42020183215pmid34950154 pmcpmc8688957 doi103389 fimmu2021795574,0.0
association dietary prebiotic consumption reduced risk alzheimer#39 s disease multiethnic population curr alzheimer res 2021 dec 21 doi 102174 1567205019666211222115142 online ahead printabstractobjective study aimed investigate association dietary prebiotic intake risk alzheimers disease ad methods longitudinal study includes 1 837 elderly 65 years participants multiethnic communitybased cohort study dementiafree baseline provided dietary information food frequency questionnaires total daily intake fructan one bestknown prebiotics calculated based consumption frequency fructan content per serving 8 food items associations daily fructan intake ad risk examined using cox proportional hazards model adjusted cohort recruitment wave age gender race ethnicity education daily caloric intake apoe genotype effect modification race ethnicity apoe genotype gender tested including interaction term cox models well stratified analysesresults among 1 837 participants 1 263 women 69 mean sd age 76 63 years 391 incident ad cases mean followup 75 years 13736 personyears additional gram fructan intake associated 24 lower risk ad 95 ci 060097 p 003 additional adjusting smoking alcohol consumption comorbidity index change results materially associations modified race ethnicity gender apoe genotype although stratified analyses showed fructan intake significantly associated reduced ad risk hispanics nonhispanic blacks whitesconclusion higher dietary fructan intake associated reduced risk clinical alzheimers disease among older adultspmid34951365 doi102174 1567205019666211222115142,0.0
levamisoleinduced leukoencephalopathy russia analysis 30 cases curr drug saf 2021 dec 24 doi 102174 1574886317666211224121517 online ahead printabstractaims raise medical specialists awareness regarding severity possible complications levamisole administration demonstrate role accurate medical history collection differential diagnosisbackground levamisole anthelmintic drug immunomodulatory effects long used worldwide till early 2000s association demyelinating leukoencephalopathy established however developing countries still widely used prevention treatment helminthic invasion humans actual prevalence levamisoleinduced multiple inflammatory leukoencephalopathy levinduced mil russia remains unknown therefore study frequency characteristics indisputably importantobjectives determine clinical features mri findings levamisoleinduced mil russian population analyse frequency diagnostic errors initial assessmentmethods singlecenter retrospective analysis total 30 patients diagnosed levinduced mil attended research center neurology conducted inclusion criteria 1 clinically acute subacute polysymptomatic onset neurological disturbances 2 mri multifocal demyelinating lesion evidence dissemination time 3 anamnestic data levamisole exposure 2 8 weeks symptoms onset well monophasic disease course absence relapses according follow assessments 3 years results clinically presentation constitutional symptoms including headache fever fatigue myalgia focal motor disturbances dysarthria prevailed cohort brain mri multiple foci demyelination simultaneous gadolinium enhancement observed link neurological symptoms levamisole intake often detected followup assessments patients often misdiagnosed acute disseminated encephalomyelitis stroke multiple sclerosis cases levinduced mil successfully treated intravenous corticosteroids plasma exchange plex however residual neurologic symptoms preserved patients additionally two detailed clinical cases patients initially misdiagnosed presented articleconclusion differential diagnosis remains difficult suspected cases levinduced mil lead delayed therapy initiation consequently incomplete recovery growing evidence suggests single administration levamisole even low doses might potentially lead severe neurological deficit death therefore changes medication management policies required order prevent uncontrolled use levamisolepmid34951579 doi102174 1574886317666211224121517,1.0
upright versus supine mri effects body position craniocervical csf flow background cerebrospinal fluid csf circulation brain spinal canal part glymphatic system provides homeostatic support brain functions waste clearance recently observed csf flow strongly driven cardiovascular brain pulsation affected body orientation advancement mri allowed noninvasive examination csf hydrodynamic properties however studies addressed relationship body position eg upright versus supine important understand csf hydrodynamics altered body position change single cardiac phase cumulative long hours staying either upright supine position can affect craniocervical csf flowmethodsin study investigate changes csf flow craniocervical region flowsensitive mri subjects moved upright supine position 30 healthy volunteers imaged upright supine positions using upright mri craniocaudal caudocranial csf flow velocity stroke volume measured c2 spinal level one cardiac cycle using phase contrast mri statistical analysis performed identify differences csf flow properties two positionsresultscsf stroke volume per cardiac cycle representing csf volume oscillating cranium 576 greater supine p 00001 due 838 increase caudocranial csf peak velocity diastole p 00001 extended systolic phase duration moving upright 025 005 s supine 034 008 s p 00001 extrapolation 24 h timeframe showed significantly larger total csf volume exchanged c2 10 h spent supine versus 5 h p 00001 conclusionsin summary body position significant effects csf flow cranium csf oscillating supine compared upright position difference driven increased caudocranial diastolic csf velocity increased systolic phase duration moving upright supine position extrapolation 24 h timeframe suggests time spent supine position increases total amount csf exchange may play beneficial role waste clearance brain,0.0
biochemical profile human infant cerebrospinal fluid intraventricular hemorrhage posthemorrhagic hydrocephalus prematurity background intraventricular hemorrhage ivh posthemorrhagic hydrocephalus phh complex pathophysiology involving inflammatory response ventricular zone cellcell junction disruption choroidplexus chp hypersecretion increased cerebrospinal fluid csf cytokines extracellular matrix proteins blood metabolites noted ivh phh osmolality electrolyte disturbances evaluated human infants conditions hypothesized csf total protein osmolality electrolytes immune cells increase phhmethodscsf samples obtained lumbar punctures control infants infants ivh prior development phh neurosurgical intervention osmolality total protein electrolytes measured 52 infants 18 controls 10 low grade lg ivh 13 high grade hg ivh 11 phh serum electrolyte concentrations csf serum cell counts within 1day clinical sampling obtained clinical charts frontal occipital horn ratio measured estimating degree ventriculomegaly dunn tukeys posttest anova analysis used pairwise comparisonsresultscsf osmolality sodium potassium chloride elevated phh compared control p 0012 00001 lgivh p 0023 00001 hgivh p 0015 00003 magnesium calcium levels higher compared control p 0031 lgivh p 0041 csf total protein higher hgivh phh compared control p 00009 00006 respectively lgivh p 0034 0028 respectively differences reflected serum electrolyte concentrations calculated osmolality across groups however quantitatively csf sodium chloride contributed 86 csf osmolality change control phh csf osmolality positively correlated csf sodium r p 055 00015 potassium r p 051 00041 chloride r p 060 00004 total protein across entire patient cohort csf total cells p 0012 total nucleated cells p 00005 percent monocyte p 0016 elevated phh compared control serum white blood cell count increased phh compared control p 0042 differences serum cell differential across groups csf total nucleated cells also positively correlated csf osmolality sodium potassium total protein p 0025 00008 whole cohortconclusionscsf osmolality increased phh largely driven electrolyte changes rather protein levels however serum electrolytes levels unchanged across groups csf osmolality electrolyte changes correlated csf total nucleated cells also increased phh suggesting phh neuroinflammatory condition,0.0
selected abstracts artery 21 n,0.0
pericytes mediators infiltration macrophages multiple sclerosis background multiple sclerosis ms neurodegenerative condition central nervous system cns associated bloodbrain barrier bbb breakdown intravasation leukocytes particularly monocytederived macrophages cns pericytes mural cells encased within basement membrane vasculature contribute functionally neurovascular unit cells play important role maintaining bbb integrity cns homeostasis however critical role pericytes mediating inflammation ms models unclear whether pericytes infiltrate cns parenchyma ms also needs clarificationmethodscns samples experimental autoimmune encephalomyelitis eae mouse model ms collected different time points immunohistochemical analysis pericytes along inflamed vasculature findings validated using ms brain specimens analysis pericyte involvement inflammation carried culturing primary pericytes macrophages multiplex elisa transmigration assay realtime pcr used study inflammatory potential pericytes culturesresultswe found pericytes exhibit heterogenous morphology notable elongation inflamed perivascular cuffs eae manifested decrease pericyte density increase coverage pericytes along vasculature chondroitin sulfate proteoglycans cspgs family extracellular matrix proteins enriched within inflamed perivascular cuffs elevated levels proinflammatory chemokines cytokines pericytes culture importantly pericytes stimulated cspgs enhanced macrophage migration detect pericytes cns parenchyma eae corroborated ms brain samplesconclusionsour data suggest pericytes seek restore bbb increased coverage exposure cspgs prompt facilitation macrophages enter cns elevate neuroinflammation eae ms,0.0
ctla4ig treatment induces m1m2 shift cultured monocytederived macrophages healthy subjects rheumatoid arthritis patients background rheumatoid arthritis ra macrophages play important role modulating immunoinflammatory response polarisation classically m1 alternatively activated m2 phenotypes ra ctla4ig abatacept reduces inflammatory activity macrophages interacting costimulatory molecule cd86 study aimed investigate efficacy ctla4ig treatment induce m2 phenotype m1polarised monocytederived macrophages mdms obtained healthy subjects hs cultured mdms obtained active ra patientsmethodscultured mdms obtained peripheral blood mononuclear cells 7 active ra patients 10 hs stimulation phorbol myristate acetate 5 ng ml 24 h hsmdms stimulated lipopolysaccharide lps 1 mg ml 4 h induce m1mdms m1mdms ramdms treated ctla4ig 100 m 500 m 3 12 24 48 h gene expression cd80 cd86 tlr4 m1 markers cd163 cd204 cd206 surface m2 markers mertk functional m2 marker evaluated qrtpcr protein synthesis surface m2 markers investigated western blotting statistical analysis performed wilcoxon ttestresultsin lpsinduced hsm1mdms ctla4ig 100 m 500 m significantly downregulated gene expression m1 markers 3 h p001 molecules 12 h p005 tlr4 cd86 significantly upregulated m2 markers primarily 12 h treatment cd163 p 001 p 005 cd206 p 005 p 001 cd204 p 005 100 mg ml moreover cells ctla4ig 500 m increased protein synthesis surface m2 markers p 005 similarly ramdms ctla4ig treatment significantly downregulated gene expression m1 markers concentrations primarily 12 h p 005 furthermore concentrations ctla4ig significantly upregulated gene expression cd206 3 h treatment p 005 cd163 mertk 12 h treatment p 005 whereas cd204 gene expression significantly upregulated high concentration ctla4ig p 005 protein synthesis surface markers increased primarily ctla4ig 500 m significantly cd204 cd206 24 h treatment p 005 conclusionsctla4ig treatment seems induce vitro shift m1 m2 macrophages hsm1mdms ramdms observed significant downregulation exerted selected m1 markers upregulation selected m2 markers suggesting additional mechanism modulation ra inflammatory process,0.0
tnf ms animal models implications chronic pain disease front neurol 2021 dec 6 12780876 doi 103389 fneur2021780876 ecollection 2021abstractmultiple sclerosis ms debilitating autoimmune disease often accompanied severe chronic pain common type pain ms called neuropathic pain arises disease processes affecting peripheral central nervous systems incredibly difficult study processes patients animal models experimental autoimmune encephalomyelitis eae mice used dissect complex mechanisms neuropathic pain ms pleiotropic cytokine tumor necrosis factor tnf critical factor mediating neuropathic pain identified animal studies tnf signaling pathway complex can lead cell death inflammation survival complex diseases ms signaling tnfr1 receptor tends proinflammation death whereas signaling tnfr2 receptor prohomeostatic however tnftargeted therapies indiscriminately block arms pathway thus therapeutic ms review explores pain ms inflammatory tnf signaling link two exploited develop effective tnftargeting pain therapiespmid34938263 pmcpmc8686517 doi103389 fneur2021780876,0.0
clinical onset multiple sclerosis relapse sarscov2 infection neurol int 2021 dec 6 13 4 695700 doi 103390 neurolint13040066abstractsevere acute respiratory syndrome coronavirus 2 sarscov2 infection associated several neurological disorders including headache facial palsy encephalitis stroke demyelinating disorders present report will discuss cases multiple sclerosis ms onset relapse beginning early sarscov2 infection cases magnetic resonance imaging mri showed widespread bilateral subcortical periventricular active lesions serum igg sarscov2 spike antigens confirmed seroconversion titers considered definitely protective possible reinfection hypothesize sarscov2 infection previously reported viruses drive active inflammatory response can contribute either onset ms relapse presented data support importance vaccination individuals mspmid34940752 doi103390 neurolint13040066,1.0
structural basis sphingosine1phosphate receptor 1 activation biased agonism nat chem biol 2021 dec 22 doi 101038 s41589021009303 online ahead printabstractsphingosine1phosphate receptor 1 s1pr1 master regulator lymphocyte egress lymph node established drug target multiple sclerosis ms mechanistically therapeutic s1pr1 modulators activate receptor yet induce sustained internalization potent association arrestin however structural basis biased agonism remains elusive report cryoelectron microscopy cryoem structures gibound s1pr1 complex s1p fingolimodphosphate fty720p siponimod baf312 combination functional assays molecular dynamics md studies reveal arrestinbiased ligands direct distinct activation path s1pr1 extensive interplay pif npxxy motifs specifically intermediate flipping w269648 retained interaction f265644 n307749 key features arrestin bias identify ligandreceptor interactions accounting s1pr subtype specificity baf312 structural insights provide rational basis designing novel signalingbiased s1pr modulatorspmid34937912 doi101038 s41589021009303,0.0
metabolomics autoimmune diseases focus rheumatoid arthritis systemic lupus erythematous multiple sclerosis metabolites 2021 nov 29 11 12 812 doi 103390 metabo11120812abstractthe metabolomics approach represents last downstream phenotype widely used clinical studies drug discovery paper outline recent advances metabolomics research autoimmune diseases ads rheumatoid arthritis ra multiple sclerosis mus systemic lupus erythematosus sle newly discovered biomarkers metabolic mechanism studies ads described addition studies elucidating metabolic mechanisms underlying ads presented metabolomics potential contribute pharmacotherapy personalization thus summarize biomarker studies performed predict personalization medicine drug responsepmid34940570 doi103390 metabo11120812,0.0
neuropathologic correlates human cortical proteins alzheimer disease related dementias neurology 2021 dec 22101212 wnl0000000000013252 doi 101212 wnl0000000000013252 online ahead printabstractbackground objectives alzheimers dementia complex clinical syndrome can defined broadly amnestic multidomain dementia previously reported human cortical proteins implicated alzheimers dementia understand pathologic correlates proteins underlying disease mechanisms investigated cortical protein associations common agerelated neuropathologiesmethods participants communitydwelling older adults two cohort studies aging dementia underwent detailed annual clinical evaluations brain autopsies performed death refer alzheimers disease ad pathologically defined disease refer alzheimers dementia clinical syndrome indices ad cortical lewy bodies limbic predominant agerelated tdp43 encephalopathy neuropathologic changes latenc hippocampal sclerosis macroscopic infarcts microinfarcts cerebral amyloid angiopathy atherosclerosis arteriolosclerosis quantified uniform structured neuropathologic evaluations highthroughput protein abundances frozen dorsolateral prefrontal cortex quantified using mass spectrometry based tandem mass tag proteomics analysis eleven human cortical proteins implicated alzheimers dementia including ace chsp1 cath doc2a ica1l lactb pkha1 rtf2 snx32 stx4 stx6 previously identified using integrative approach logistic regression analysis examined association protein expression neuropathologic indicesresults total 391 older adults included observe associations protein targets pathologic diagnosis ad contrast multiple proteins associated nonad neurodegenerative cerebrovascular conditions particular higher chsp1 expression associated cortical lewy bodies macroscopic infarcts higher cath expression associated latenc arteriolosclerosis higher stx6 expression increased risk alzheimers dementia protein associated neuropathologic indices investigateddiscussion cortical proteins implicated alzheimers dementia necessarily work ad pathogenesis rather nonad neurodegenerative vascular diseases well pathways play proteins pleiotrophic associated neurodegenerative cerebrovascular pathologiespmid34937778 doi101212 wnl0000000000013252,0.0
clinical profile imaging features short term visual outcomes indian optic neuritis patients without seromarkers myelin oligodendrocyte glycoprotein neuromyelitis optica indian j ophthalmol 2022 jan 70 1 194200 doi 104103 ijoijo_887_21abstractpurpose analyze clinical profile imaging features shortterm visual outcomes optic neuritis patients indian population without seromarkers myelin oligodendrocyte glycoprotein mog neuromyelitis optica nmo methods electronic medical records 203 optic neuritis patients presented june 2018 december 2019 neuroophthalmology services tertiary care center india retrospectively analyzedresults 203 patients 57 patients 2808 positive mogantibody 20 patients 985 positive nmo antibody 114 patients 5616 doublenegative negative antibodies 12 patients 591 diagnosed multiple sclerosis ms none patients antibodies mean age presentation 3129 1035 years female preponderance nmooptic neuritis nmoon msoptic neuritis mson groups 15 mean vision presentation worse logmar 1570 0863 nmoon group mean visual acuity showed statistically significant recovery logmar 0338 0639 final followup mogoptic neuritis mogon group multivariate logistic regression analysis revealed poor visual outcome patients presenting retrobulbar neuritis optic disc pallor bilateral sequential optic nerve involvement positive nmo antibody optic neuritis patients presenting disc edema associated pain positive mog antibody found better visual outcomeconclusion indian optic neuritis cohort prevalence mogon higher nmoon mogon better visual outcome nmoon incidence mson less compared western literature significant number patients 114 patients 5616 double negative seromarkers yet presented optic neuritis clinical imaging features suggestive ms mog associated disease mog ad nmo spectrum disorder nmo sd pmid34937238 doi104103 ijoijo_887_21,1.0
assessment neurologic signs symptoms establishing diagnosis multiple sclerosis prim care companion cns disord 2021 dec 23 23 6 20f02871 doi 104088 pcc20f02871abstractthe psychiatric consultation service massachusetts general hospital sees medical surgical inpatients comorbid psychiatric symptoms conditions twiceweekly rounds dr stern members consultation service discuss diagnosis management hospitalized patients complex medical surgical problems also demonstrate psychiatric symptoms conditions discussions given rise rounds reports will prove useful clinicians practicing interface medicine psychiatrypmid34942063 doi104088 pcc20f02871,0.0
association ebv hhv6 viral load different nk cd8 + t cell subsets acute phase relapsingremitting multiple sclerosis cell j 2021 nov 23 6 626632 doi 1022074 cellj20217308 epub 2021 nov 23abstractobjective epsteinbarr virus ebv human herpes virus 6 hhv6 believed involve multiple sclerosis ms pathogenesis natural killer nk cd8+ t cells essential roles handling viral infections phenotypic functional properties may influenced following exposure viral infections investigated association nk cd8+ t cells subpopulations frequency ebv hhv6 viral load ms patientsmaterials methods casecontrol study ebv hhv6 viral load evaluated plasma newly diagnosed relapsingremitting ms rrms patients relapse phase n23 diseasemodifying therapy dmt sex agematched healthy controls n19 using realtime polymerase chain reaction pcr frequency nk cd8+ t cells subsets assessed cd27 cd28 cd45ro cd56 cd57 markers using flow cytometryresults despite increased level ebv viral load rrms patients compared control group statistically significant difference ebv hhv6 copy numbers studied groups addition significant decrease observed percentages cd56bright cd57 cd56dim cd57+ cd8low cd45ro nk cells rrms patients comparison healthy controls analysis cd8+ t cell subsets showed substantially high proportion cd27+ cd28+ cd45ro+ cd57 cd8hi t cells patients relapse phase compared controls frequency nk t cells subtypes associated ebv hhv6 plasma viral loadsconclusion findings highlight variation nk cd8+ t cells subsets frequency clinically active rrms patients since composition cells associated ebv hhv6 viral load perhaps viral infections may involved altered nk cd8+ t cells subpopulation larger cohort studies needed confirm resultspmid34939755 doi1022074 cellj20217308,0.0
hepatotoxicity associated use teriflunomide patient multiple sclerosis case report medicine baltimore 2021 dec 23 100 51 e28246 doi 101097 md0000000000028246abstractrationale teriflunomide inhibitor pyrimidine synthesis available firstline treatment relapsingremitting multiple sclerosis druginduced liver damage relevant problem clinical practice representing frequent cause treatment discontinuation case report describes occurrence liver injury 337fold increase upper limit normality liver enzyme alanine aminotransferase treatment teriflunomide 14 mgpatient concern 44yearold woman receiving teriflunomide 14 mg treatment multiple sclerosis presented symptoms suggestive liver dysfunction 54 days starting treatment patient history using diseasemodifying therapy neither previous liver disease comorbiditiesdiagnostics suggested diagnosis druginduced liver injury classified hepatocellular possible hepatic autoimmune etiologies ruled outinterventions replacement teriflunomide treatment glatiramer acetate followup diseaseoutcomes signs symptoms regressed treatment teriflunomide 14 mg discontinued normalization liver enzyme activity 5 months causality assessment adverse drug reaction determined naranjo scaling system resulting probable final score 7conclusions teriflunomideinduced liver injury patients multiple sclerosis serious adverse reaction report case contributes updating knowledge safety aspects treatment teriflunomide planning monitoring strategies patient risk managementpmid34941096 doi101097 md0000000000028246,0.0
multiple sclerosis viruses new vaccines neurol int 2021 dec 13 13 4 712714 doi 103390 neurolint13040068abstractmultiple sclerosis ms common inflammatory neurological disease young adults estimated prevalence approximately 2 pmid34940754 doi103390 neurolint13040068,0.0
management adult tuberous sclerosis complexrelated angiomyolipoma singlecenter experience can urol assoc j 2021 dec 21 doi 105489 cuaj7556 online ahead printabstractintroduction tuberous sclerosis complex tsc rare multisystem genetic disease significant cause tscrelated morbidity potential bleeding renal angiomyolipoma aml preemptively decrease aml bleeding mtor inhibitors can used however thresholds initiating maintaining everolimus therapy remain uncertain recent literature suggests triggering active treatment amls based size thresholds alone evaluated appropriateness initiating everolimus therapy asymptomatic patients considering aml size rate growth factorsmethods diagnostic criteria developed 2012 international tsc consensus group presence aml used inclusion criteria medical imaging reports 20 tsc patients single center reviewedresults mean age 4055 1627 11 patients female eight asymptomatic patients high risk complications underwent everolimus therapy seven 88 demonstrated decreased aml size multiple side effects reported four highrisk asymptomatic patients undergo therapy due side effect concerns four lowrisk asymptomatic patients stable amls active surveillance four patients reduced amls local therapyconclusions everolimus treatment effective managing aml size highrisk asymptomatic patients tolerable side effects aml size can remain relatively stable asymptomatic lowrisk patients despite receiving intervention s patients tscrelated making including factors bleeding risk aml growth rate number absolute size amlspmid34941491 doi105489 cuaj7556,0.0
multiple sclerosis children differential diagnosis prognosis diseasemodifying treatment cns drugs 2021 dec 23 doi 101007 s4026302100887w online ahead printabstractpediatriconset multiple sclerosis poms rare neuroinflammatory neurodegenerative disease significant impact longterm physical cognitive patient outcomes small percentage multiple sclerosis ms diagnoses occur age 18 years treatment initiation careful differential diagnosis exclusion similar acquired demyelinating syndromes antiaquaporin4associated neuromyelitis optica spectrum disorder aqp4nmosd myelin oligodendrocyte glycoprotein antibody spectrum disorder mogsd warranted recent 2017 changes mcdonald criteria can successfully predict 71 ms diagnoses good specificity 95 sensitivity 71 additional measures presence t1weighted hypointense lesions contrastenhancing lesions significantly increase accuracy diagnosis adults early use diseasemodifying therapies dmts instrumental better longterm prognosis including lower rates relapse disability worsening numerous fdaapproved therapies adultonset ms available however unlike adult counterparts development testing regulatory approval poms treatments significantly slower hindered logistic ethical considerations currently two ms dmts fingolimod teriflunomide tested large phase iii trials approved regulatory agencies use poms firstline therapies approved fda use children interferon glatiramer acetate also commonly used result significant reduction inflammatory activity compared nontreated poms patients increasing number poms patients now treated moderate efficacy therapies dimethyl fumarate highefficacy therapies natalizumab anticd20 monoclonal antibodies anticd52 monoclonal antibodies autologous hematopoietic stem cell transplantation highefficacy dmts generally provide additional reduction inflammatory activity compared firstline medications 62 relapserate reduction therefore number phase ii iii trials currently investigating efficacy safety poms patients review discuss potential changes regulatory approval process poms patients recommended dmts already approved adult ms population including smaller sample size pharmacokinetic pharmacodynamic studies mricentered primary outcomes inclusion teenagers adult trialspmid34940954 doi101007 s4026302100887w,1.0
qosmos study pharmacistled multicentered observational study quality life multiple sclerosis neurol int 2021 dec 3 13 4 682694 doi 103390 neurolint13040065abstracthealthrelated quality life frequently included patientreported outcomes aimed evaluating effectiveness diseasemodifying drugs multiple sclerosis recent data italian patients missing multicenter observational crosssectional study performed students hospital pharmacy update existing data quality life correlate pharmacological medical history patients quality life qol assessed using msqol54 questionnaire pharmacist collected patients characteristics medical pharmacological history expanded disability status scale edss three hundred fortynine patients multiple sclerosis recruited 16 centers may 2018 june 2019 median age 441 years 689 women composite indexes physical mental wellbeing showed direct correlation r 0826 p 0001 edss disability independent negative predictor indexes r2 3508 p 0001 r2 1574 p 0001 respectively trend association physical health composite score different classes oral diseasemodifying drugs dmds observed study found decrease qol correlated teriflunomide deserves investigation experience demonstrates joint action scientific society students association can successful conducting noprofit multicenter observational study realworld settingpmid34940751 doi103390 neurolint13040065,0.0
ocular manifestations multiple sclerosis patients three countries webbased survey eur j ophthalmol 2021 dec 2311206721211069457 doi 101177 11206721211069457 online ahead printabstractobjective study evaluates epidemiological characteristics ophthalmological manifestations different therapeutic options available patients multiple sclerosis ms china spain cubamethods selfdesigned questionnaire used conduct comparable descriptive crosssectional study patients ms survey included patients demographic data ocular manifestations related ms treatment methodology followed three countries online survey designed using wenjuanxing survey platform survey link circulated whatsapp wechat emails quantitative data expressed mean standard deviation kruskalwallis test used nonparametric variables qualitative data expressed numerical percentage chisquare test 2 used compare groups response categories statistical difference considered significant p 005results femaletomale ratio three countries 231 relapsingremitting ms rrms frequent three countries vision loss slow progressive half patients three countries significant differences p 0524 higher percentage steroid treatment observed chinese patients comparison patients two countries p 0001 similar trend seen use traditional medicines almost onethird patients receive treatment recovered spontaneously three countries p 0097 conclusions ms occurs frequently relapsingremitting clinical form clear female predominance first ocular crisis clinical debut ms characterized slow progressive visual impairment increasing adding ocular manifestations evolutionary course spontaneous recovery vision attack optic neuritis course ms possiblepmid34939452 doi101177 11206721211069457,0.0
scavenging hidden impacts noncoding rnas multiple sclerosis noncoding rna res 2021 dec 7 6 4 187199 doi 101016 jncrna202112002 ecollection 2021 decabstractmultiple sclerosis ms chronic neuroinflammatory disease causes severe neurological dysfunction leading disabilities patients prevalence disease increasing gradually worldwide specific etiology behind disease yet fully understood therapies aimed treating ms patients growing lately intending delay disease progression increase patients quality life various pathways play crucial roles developing disease several therapeutic approaches tackling pathways however strategies shown several side effects inconsistent efficacy micrornas mirnas long noncoding rnas lncrnas circular rnas circrnas shown act key players various disease pathogenesis development several proinflammatory antiinflammatory mirnas reported participate development ms hence review assesses role mirnas lncrnas circrnas regulating immune cell functions better understand impact molecular mechanics mspmid34938929 pmcpmc8666456 doi101016 jncrna202112002,0.0
difficulty identification patients active secondary progressive multiple sclerosis clinical classification tools eur j neurol 2021 dec 22 doi 101111 ene15227 online ahead printabstractbackground transition relapsingremitting rrms secondary progressive spms multiple sclerosis well defined different definitions tools identify spms proposed meanwhile early diagnosis active spms getting progressively important pharmaceutical treatment options developed study compared different classification methods regarding accuracy reliably identify active spmsmethods independent previous diagnostic classification descriptively analyzed disease course regarding relapses progression mractivity 208 consecutive multiple sclerosis patients treated ms outpatient clinic 2018 patients reclassified according different spms criteria tools diagnostic accuracy identify patients active spms determinedresults comparing tools significant variability number patients identified spms well proportion patients active spms noted applying diagnostic criteria spms active disease reduced sensitivity identify patients active progressive disease approachesconclusion propose lessen emphasis label spms favor open term active progressive disease simplify process identification patients may benefit immune therapypmid34939266 doi101111 ene15227,0.0
metagenomic analysis pediatriconset multiple sclerosis gut microbiome neurology 2021 dec 22101212 wnl0000000000013245 doi 101212 wnl0000000000013245 online ahead printabstractbackground objectives little known functional potential gut microbiome pediatriconset multiple sclerosis ms performed metagenomic analyses using stool samples individuals pediatriconset ms unaffected controlsmethods persons 21 years old enrolled canadian pediatric demyelinating disease network providing stool sample eligible twenty ms patients mcdonald criteria symptom onset 18 years matched 20 controls sex age 3 years stool consistency race microbial taxonomy functional potentials estimated stool samplederived metagenomic reads compared disease status ms vs controls diseasemodifying drug dmd exposure using alphadiversity relative abundance prevalence using wilcoxon ranksum aldex2 fishers exact tests respectivelyresults individuals ms aged 136 years mean symptom onset 8 dmd nave mean ages stool sample 161 154 years ms control participants respectively 80 girls alphadiversity enzymes proteins differ disease dmd status p020 metabolic pathways gene annotations microbial taxonomy individuals ms vs controls exhibited higher methanogenesis prevalence odds ratio10 p0044 methanobrevibacter abundance log2 foldchange lfc 17 p00014 lower homolactic fermentation abundance lfc048 p0039 differences dmd status included lower phosphate butyryltransferase dmdnave vs exposed ms patients lfc10 p0033 discussion gut microbiomes functional potential taxonomy differed individuals pediatriconset ms versus controls including higher prevalence methaneproducing pathway archaea depletion lactate fermentation pathway dmd exposure associated butyrateproducing enzyme enrichment together findings indicate gut microbiome individuals ms may disturbed functional potentialpmid34937787 doi101212 wnl0000000000013245,1.0
impact metabolic disorders structural functional immunological integrity bloodbrain barrier therapeutic avenues abstractmounting evidence linked metabolic disease neurovascular disorders cognitive decline using murine model highfat highsugar diet mimicking obesityinduced type 2 diabetes mellitus t2dm humans show proinflammatory mediators altered immune responses damage bloodbrain barrier bbb structure triggering proinflammatory metabolic phenotype find disruption tight junctions basal lamina due loss control production matrix metalloproteinases mmps inhibitors timps causes bbb impairment together disruption structural functional integrity bbb results enhanced transmigration leukocytes across bbb contribute initiation neuroinflammatory response activation microglia using humanized vitro model bbb t2dm patient postmortem brains show translatable applicability results find leaky bbb phenotype t2dm patients can attributed loss junctional proteins changes inflammatory mediators mmp timp levels resulting increased leukocyte extravasation brain parenchyma investigated therapeutic avenues reduce restore bbb damage caused hfhsfeeding pharmacological treatment recombinant annexin a1 hranxa1 reversion highfat highsugar diet control chow diet dietary intervention attenuated t2dm development reduced inflammation restored bbb integrity animals given rising incidence diabetes worldwide understanding metabolicdiseaseassociated brain microvessel damage vital proposed therapeutic avenues help alleviate burden diseases,0.0
pharmaceutical subsidy policy iran qualitative stakeholder analysis background past three decades allocation foreign currency subsidies primary strategy various administrations iran improve access medicines strategy resulted several challenges including stakeholder conflicts interestobjectiveto identify power interest role stakeholders allocating foreign currency subsidies medicines iranian health systemmethodsin qualitative study 39 semistructured interviews conducted key informants recruited using purposive sampling technique theoretical framework adopted varvasovszky brugha employed data analysed using directed content analysisresultsthe foreign currency subsidy medicines included 21 stakeholders five main categories governmental organizations iranian parliament general population nongovernmental organizations ngos pharmaceutical industry stakeholders varied level participation support policymaking process among iranian government planning budget organization ministry health medical education mohme iran food drug administration ifda important stakeholders highly supportive positions domestic drug manufacturers strongest opponents policy government iran powerful institution regard ability allocate foreign currency subsidies medicines followed mohme ifdaconclusionthis study demonstrated identifying analysing stakeholders involved allocating foreign currency subsidies medicines can provide valuable information policymakers enable comprehensive understanding better capacity determine whether eliminate subsidies moreover decisionmaking process longterm issue requires consensus among stakeholders political social consequences eliminating foreign currency subsidies necessary political will institutionalized recommend stepbystep approach eliminating foreign currency subsidies requirements met ie related consequences interventions therefore revision current policy along requirements addition financial transparency enhanced efficiency will facilitate progress towards achieving sustainable development goals improving access medicines,0.0
microglia astrocyte involvement neurodegeneration brain cancer abstractthe brain unique complex organ body containing neurons several types glial cells different origins properties protect ensure normal brain structure function neurological disorders result failure nervous system multifaceted cellular networks although great progress made understanding glia involvement neuropathology therapeutic outcomes still satisfactory discuss recent perspectives role microglia astrocytes neurological disorders including two common neurodegenerative conditions alzheimer disease progranulinrelated frontotemporal lobar dementia well astrocytoma brain tumors emphasize key factors microglia astrocytic biology highly heterogeneic glial nature strongly dependent environment genetic factors predispose certain pathologies glia senescence inevitably changes cns landscape understanding diverse glial contributions neurological diseases can lead advances glial biology functional recovery cns malfunction,0.0
synaptic integration subquantal neurotransmission colocalized g proteincoupled receptors presynaptic terminals presynaptic terminals membranedelimited gi omediated presynaptic inhibition ubiquitous acts g inhibit ca2+ entry directly snare complexes inhibit ca2+dependent synaptotagminsnare complex interactions ca1subicular presynaptic terminals 5ht1b gabab receptors colocalize gabab receptors inhibit ca2+ entry whereas 5ht1b receptors target snare complexes demonstrate male female rats gabab receptors receptors alter pr whereas 5ht1b receptors reduce evoked cleft glutamate concentrations allowing differential inhibition ampa nmda receptor epscs reduction cleft glutamate concentration confirmed imaging glutamate release using genetic sensor iglusnfr simulations glutamate release postsynaptic glutamate receptor currents made tested effects changes vesicle numbers undergoing fusion single synapses relative placement fusing vesicles postsynaptic receptors rate release glutamate fusion pore experimental effects pr changes consistent gabab receptor effects straightforwardly represented changes numbers synapses effects 5ht1b receptormediated inhibition wellfit simulated modulation release rate glutamate cleft colocalization different actions gpcrs provide synaptic integration within presynaptic terminals traindependent presynaptic ca2+ accumulation forces frequencydependent recovery neurotransmission 5ht1b receptor activation consistent competition ca2+synaptotagmin g snare complexes thus stimulus trains 5ht1b receptor agonist unveil dynamic synaptic modulation sophisticated hippocampal output filter modulated colocalized gabab receptors alter presynaptic ca2+ combination pathways allow complex presynaptic integrationsignificance statementtwo g protein coupled receptors colocalize presynaptic sites mediate presynaptic modulation g one gabab receptor inhibits ca2+ entry another 5ht1b receptor competes ca2+synaptotagmin binding synaptic vesicle machinery investigated downstream effects signaling integrative properties receptors effects profoundly different gabab receptors alter pr leaving synaptic properties unchanged 5ht1b receptors fundamentally change properties synaptic transmission modifying ampa receptor sparing nmda receptor responses coactivation receptors allows synaptic integration convergence gabab receptor alteration ca2+ effect altered ca2+ signal 5ht1b receptor signaling presynaptic convergence provides novel form synaptic integration,0.0
density strips visualisation uncertainty clinical data summaries research findings bmj evid based med 2021 dec 21bmjebm2021111746 doi 101136 bmjebm2021111746 online ahead printabstractthe disproportionate focus statistical significance reporting interpreting clinical research studies contributes publication bias encourages selective reporting highlights need alternative approaches clearly communicate uncertainty data enabling researchers provide nuanced interpretation clinical research findingsour purpose article introduce density strip method one potential approach might act bridge data visualisation descriptive purposes formal statistical inference build existing theory translating applied research context illustrate utility clinical researcherswe achieve considering exemplar clinical trial multiple sclerosissecondary progressive multiarm randomisation trial mssmart mssmart multiarm randomised placebocontrolled trial three potentially neuroprotective drugs secondary progressive ms illustrate mssmart potential density strip effective visualisation distribution clinical trial outcomes complementary approach aid interpretation formal inferential statistical analysiswe conclude summarising advantages disadvantages density strip methodology provide suggestions potential extensions possible usespmid34933930 doi101136 bmjebm2021111746,1.0
bloodcsfbrain route neurological disease indirect pathway brain neuropathol appl neurobiol 2021 dec 21 doi 101111 nan12789 online ahead printabstractthe brain protected endothelial bloodbrainbarrier bbb limits access microorganisms tumour cells immune cells autoantibodies parenchyma however classic model disease spread across disrupted bbb explain focal distribution lesions seen variety neurological diseases lesions frequently adjacent cerebrospinal fluid csf spaces critically reviewed possible role bloodcsfbrain route disease entry pathway brain parenchyma initial step pathway transfer pathogens immune components blood csf choroid plexuses bloodcsfbarrier bcsfb located flow csf results disease dissemination throughout csf spaces access brain parenchyma csf can occur across ependymal layer ventricular surface across pialglial barrier subarachnoid space virchowrobin spaces reviewed anatomy physiology bloodcsfbrain pathway brain barriers controlling process summarised evidence supporting brain entry route crosssection neurological diseases including neuromyelitis optica multiple sclerosis neurosarcoidosis neuropsychiatric lupus cryptococcal infection solid haematological tumours summary highlights conditions share bloodcsfbrain pathway pathogenetic mechanism include characteristic proximity lesions csf evidence disruption brain barriers identification significant pathology within csf improved understanding pathological transfer csf across brain barriers will inform effective targeted treatments primary secondary disease central nervous systempmid34935179 doi101111 nan12789,0.0
colonystimulating factor1 receptor inhibition attenuates microgliosis myelin loss exacerbates neurodegeneration chronic cuprizone model j neurochem 2021 dec 22 doi 101111 jnc15566 online ahead printabstractmultiple sclerosis ms especially progressive phase involves early axonal neuronal damage resulting combination inflammatory mediators demyelination loss trophic support progressive disease stages microenvironment created within central nervous system cns favoring arrival retention inflammatory cells active demyelination neurodegeneration also linked microglia mg astrocyte ast activation early lesions reactive mg can damage tissue exacerbate deleterious effects contribute neurodegeneration noted activated mg possess neuroprotective functions well including debris phagocytosis growth factor secretion progressive form ms can modelled prolonged administration cuprizone cpz adult mice cpz induces highly reproducible demyelination different brain regions oligodendrocyte olg apoptosis accompanied mg ast activation axonal damage therefore goal evaluate effects reduction microglial activation orally administered brainpenetrant colonystimulating factor1 receptor csf1r inhibitor blz945 blz neurodegeneration correlation demyelination astroglial activation behavior chronic cpzinduced demyelination model results show blz treatment successfully reduced microglial population myelin loss however correlation found myelin preservation neurodegeneration axonal degeneration prominent upon blz treatment concomitantly blz failed significantly offset cpzinduced astroglial activation behavioral alterations results taken account proposing modulation microglial activation design therapies relevant demyelinating diseasespmid34935149 doi101111 jnc15566,1.0
adaptive platform trials transform als therapy development ann neurol 2021 dec 21 doi 101002 ana26285 online ahead printabstractcurrent therapeutic development als relies individual randomized clinical trials test specific investigational product single patient population approach intrinsic limitations including cost time lack flexibility adaptive platform trials represent novel approach investigate several interventions single disease continuous manner already use oncology approach now employed often neurology describe newly launched platform trial amyotrophic lateral sclerosis als healey als platform trial testing multiple investigational products concurrently people als goal rapidly identifying novel treatments biomarkers trial endpoints article protected copyright rights reservedpmid34935174 doi101002 ana26285,0.0
effect fluoxetine treatment neurotoxicity induced lysolecithin male rats can j physiol pharmacol 2021 dec 22110 doi 101139 cjpp20210077 online ahead printabstractdemyelination disorder unusual pathologic event occurs central nervous system cns multiple sclerosis ms inflammatory demyelinating disease affects cns leading cause disability young adults lysolecithin lpc one best toxininduced demyelination models study suitable model created effect fluoxetine treatment examined model case assumed daily fluoxetine treatment increased endogenous remyelination lpc model study focused investigating influence fluoxetine dose 5 10 mg kg per day 1 4 weeks lpcinduced neurotoxicity corpus callosum region performed demyelinating model male wistar rats 3 days fluoxetine injected intraperitoneally 5 10 mg kg per day 1 4 weeks group completing treatment course corpus callosum removed examine gene expression histological analysis performed results histopathological study hematoxylin eosin staining corpus callosum showed 1 4week treatment groups fluoxetine reduced level inflammation lpc injection site 5 10 mg kg per day fluoxetine treatment luxol fast blue lfb staining corpus callosum led increase myelination capacity doses times results genetic study showed fluoxetine significantly reduced expression level tumor necrosis factor nuclear factor induced nitric oxide synthase comparison untreated lpc group also fluoxetine treatment enhanced expression level forkhead box p3 foxp3 gene comparison untreated group fluoxetine increased expression level myelination neurotrophic genes myelin basic protein mbp oligodendrocyte transcription factor 2 olig2 brainderived neurotrophic factor bdnf outcomes demonstrated fluoxetine reduces inflammation strengthens endogenous myelination lpcinduced demyelination model however supplementary studies required specifying details mechanismspmid34935529 doi101139 cjpp20210077,1.0
therapeutic potentials poly adpribose polymerase 1 parp1 inhibition multiple sclerosis animal models concept revisiting adv sci weinh 2021 dec 21e2102853 doi 101002 advs202102853 online ahead printabstractpoly adpribose polymerase 1 parp1 plays fundamental role dna repair gene expression excessive parp1 hyperactivation however associated cell death parp1 activity dysregulated immune central nervous system multiple sclerosis ms patients animal models pharmacological parp1 inhibition shown protective immune activation disease severity ms animal models genetic parp1 deficiency studies reported discrepant results inconsistency suggests function parp1 parp1mediated parylation may complex contextdependent article reviews parp1 functions discusses experimental findings possible interpretations parp1 inflammation neuronal axonal degeneration oligodendrogliopathy three major pathological components cooperatively determining ms disease course neurological progression points future research directions cell type specific parp1 manipulations necessary revisiting role parp1 three pathological components prior moving parp1 inhibition clinical trials ms therapypmid34935305 doi101002 advs202102853,0.0
incidence risk cancer among multiple sclerosis patients matched populationbased cohort study eur j neurol 2021 dec 22 doi 101111 ene15226 online ahead printabstractbackground studies yet found conclusive results risk cancer patients multiple sclerosis ms study aimed compare incidence cancers specific types cancer ms patients general population age sexmethods prevalent ms patients identified 20082014 nationwide french healthcare database snds without history malignancy included cohort study followedup cancer occurrence date death 31 december 2015 whichever came first ms patients matched based sex year birth nonms controls general population without cancer index date incidence rate reported per 100 000 personyear py risk cancer estimated type cancer age sex using cox model hazard ratio hrs 95 confidence intervals 95ci results overall 576 cancers per 100 000 py observed ms patients versus 424 per 100 000 py control population risk cancer higher among ms patients among population controls whether considered overall hr 136 95ci 129143 prostate hr 208 95ci 168258 colorectal anal hr 135 95ci 116158 trachea bronchus lung hr 236 95ci 196284 lesser extent breast cancer hr 112 95ci 103123 conclusion ms patients associated increased risk cancer compared population controlspmid34936169 doi101111 ene15226,0.0
multiple sclerosis caregiving systematic scoping review map current state knowledge health soc care community 2021 dec 22 doi 101111 hsc13687 online ahead printabstractunpaid caregivers typically family friends provide significant amounts support people multiple sclerosis ms understanding experiences needs challenges necessary ensure caregivers receive support require continue role aim map current state knowledge unpaid caregivers people ms identify gaps knowledge guide future research practice used scoping review methodology three major healthrelated databases medline cinahl apa psychinfo searching september 2019 april october 2020 october 2021 selected peerreviewed scientific articles reporting primary studies unpaid caregivers people ms regardless topic research design extracted information study aim participant characteristics measures used key findings generate major themes identify knowledge gaps identified 108 published studies 1992 2021 met criteria studies spousal caregivers common studies focused primarily measurement caregiver burden negative consequences caregiving thirteen studies addressed positive consequences caregiving sixteen studies reported actual tasks performed caregivers seven reported outcomes caregiver support interventions attention diversity issues may influence caregiving experiences outcomes rare overall knowledge ms caregiving limited particularly respect tasks performed caregivers may contribute negative outcomes diversity issues effective approaches remediate caregiver burden without knowledge finding ways better support ms caregivers will difficultpmid34935217 doi101111 hsc13687,0.0
exploratory study regarding communication facilitators barriers reported cohort multiple sclerosis ms community members international massive open online course understanding ms abstractbackgroundeffective communication essential highquality multiple sclerosis ms related healthcare significant knowledge practice gaps remain area aim study explore facilitators barriers communication ms reported members ms communitymethodswe conducted exploratory mixed method study analysing selfreported facilitators barriers communication among ms community members participating free international online course ms called understanding ms commented optional discussion board quantitatively compared commenters course participants comment among commenters compared health information consumers people ms caregivers suppliers healthcare providers service providers researchers using chi square ttests evaluated free text discussion board responses emergent themes comparing contrasting consumer supplier responsesresultswe found sociodemographic characteristics commenters n262 similar course participants overall including age sex ms community role however among commenters consumers n152 9 years older suppliers n57 average mean age consumers 529 years suppliers 440 years p0001 less likely university degree p0004 live australia course host country representing almost 60 cohort p0001 nonetheless consumers suppliers listed similar facilitators communication ms honesty kindness empathy compassion openness effective listening consumers prioritized clarity patience consumers also likely list barriers communication commonly listing following barriers encountering lack knowledge ms invisible symptoms ms uncertainty appropriate amount communication concern perceived complaining burdening others finally consumers also discussed communication means educate others msconclusionseffective communication remains challenge ms community particularly health information suppliers health information consumers results exploratory study highlight areas considered developing communication strategies ms community members larger confirmatory study ms health information consumers suppliers uses focus groups individual interviews conducted explore emerging themes,0.0
mitophagy neurological disorders abstractselective autophagy evolutionarily conserved mechanism removes excess protein aggregates damaged intracellular components eukaryotic cells including neurons rely proficient mitophagy responses finetune mitochondrial number preserve energy metabolism circumstances presence pathogenic protein oligopolymers protein mutations dysfunctional mitophagy leads nerve degeneration agedependent intracellular accumulation protein aggregates dysfunctional organelles leading neurodegenerative disease however pathogenic protein oligopolymers protein mutations stress injury present mitophagy prevents accumulation damaged mitochondria accordingly mitophagy mediates neuroprotective effects forms neurodegenerative disease eg alzheimers disease parkinsons disease huntingtons disease amyotrophic lateral sclerosis acute brain damage eg stroke hypoxicischemic brain injury epilepsy traumatic brain injury complex interplay mitophagy neurological disorders suggests targeting mitophagy might applicable treatment neurodegenerative diseases acute brain injury however due complexity mitophagy mechanism mitophagy can harmful beneficial future efforts focus maximizing benefits discuss impact mitophagy neurological disorders emphasizing contrast positive negative effects mitophagy,1.0
computational basis decisionmaking impairment multiple sclerosis abstractbackgroundmultiple sclerosis ms commonly associated decisionmaking neurocognitive impairments mood motivational symptoms however relationship may obscured traditional scoring methodsobjectivesto study computational basis underlying decisionmaking impairments ms interaction neurocognitive neuropsychiatric measuresmethodstwentynine ms patients 26 matched control subjects completed computer version iowa gambling task igt participants underwent neurocognitive evaluation using expanded version brief repeatable battery hierarchical bayesian analysis used estimate three established computational models compare parameters groupsresultspatients showed increased learning rate reduced lossaversion decisionmaking relative control subjects alterations associated 1 reduced net gains igt 2 processing speed executive functioning memory impairments 3 higher levels depression current apathyconclusiondecisionmaking deficits ms patients described interplay latent computational processes neurocognitive impairments mood motivational symptoms,0.0
stable multiple sclerosis patients anticd20 therapy go extended interval dosingyes introductionanticd20 antibodies rituximab proved powerful yet remained offlabel treatment multiple sclerosis ms approval ocrelizumab 2018 drugfree intervals two courses bcell depletion long treatment efficacy determined prolonged immunosuppression can eventually assessed peripheral bcell reconstitution provides opportunity individually delay therapy known extended interval dosing eid likely beneficial view safety concerns specifically aside frequent infusion reactions continuous bcell depletion might associated longterm immunological complications increased risk malignancy hypogammaglobulinemia latter turn likely result higher infection rates reduced vaccine efficacy finally eid may also provide sufficient time drugfree pregnancy ongoing protection disease activityin light notable recent studies number mechanistic features argue favor durable efficacy beyond standard 6monthly dosing 20 patients treated rituximab even fewer 5 ocrelizumab began repopulate 6 months cd19+ repopulation took longer one year1 although potential anticd20 antibodies deplete bcell subsets yet fully elucidated agents deplete memory bcells 2 can last years treatment marked depletion memory bcells also appears common feature contributing efficacy socalled immune reconstitution therapies irt show longterm efficacy short treatment cyclesimpact eid anticd20 therapies disease activity patient safetyseveral studies showed eid two infusions rituximab ocrelizumab ms associated low risk disease activity recently published large multicenter study compared ocrelizumabtreated ms patients eid control group standard interval dosing 3 months last treatment cycle3 differences groups terms relapses confirmed progression disease neda3 status suggesting eid affect efficacy least shortterm evaluation similar findings observed baker et al4 longer followup periods specifically using data openlabel phase ii ocrelizumab extension trial demonstrated 12 18 months last infusion following three cycles ocrelizumab levels disease activity appear similar seen phase iii extension studies following six cycles ocrelizumab4 likewise smaller realworld studies supported longer treatmentfree intervals ocrelizumab ms without lack efficacy5 line phase extension study rituximab ms reported maintained benefit 12 months last infusion2 moreover offlabel studies rituximab treatment halted demonstrated longacting benefit absence rebound disease activity stopping therapy6 7regarding safety concerns one study showed fewer overall adverse events infections eid cohorts4 addition recently indicated delaying anticd20 infusions 3 6 months increases likelihood developing adequate humoral response covid19 vaccination8taken together findings make convincing argument bcelldepleting agents induce durable inhibition relapsing disease consequently likely efficacy can maintained reducing frequency dosing limiting infections risks associated continued immunosuppression allowing effective vaccinationpersonalized bcellbased treatment regimens timetoinfusion decisionmakingit repeatedly hypothesized continuous monitoring peripheral cd19+ bcells may sufficient guide individualized decisionmaking regarding reinfusion intervals indeed studies investigating rituximab autoimmune conditions indicated low levels cd19+ bcells serve surrogate marker justify delaying bcelldepleting infusions however evidence personalized bcelltailored eid ms patients remains controversial although eid anticd20 antibodies represented predictor repopulation cd19+ bcells several studies 5 7 9 one study showed therapeutic effect closely associated absence cd19+ bcells9 contrast association absolute cd19+ bcell number reemerging disease activity evident studies 3 7 suggesting effects rituximab ocrelizumab ms maintained cd19+ bcell repopulationof note detailed assessment bcells periphery including cd19+ cd27+ memory bcells shown reliable prediction clinical activity indeed preliminary study rituximab suggests dosing according memory bcell population kinetics reduces dosing frequency maintaining efficacy ms10 monitoring peripheral b memory cells demonstrated biomarker activity autoimmune diseases including neuromyelitis optica myasthenia gravisconclusionoverall findings indicate eid can performed without detrimental impact effectiveness improving patient safety although complex mechanisms underlying observed effects remain unclear findings suggest anticd20 antibodies likely possess features irta major challenge ms research now elucidate exact impact anticd20 antibodies immune system determine surrogate markers individual timetoinfusion decisionmaking context memory bcell repopulation rate appears promising candidate appraise individually adapted therapy intervalsthus concentrate research efforts headtohead studies anticd20 therapy extended doses compared current standard including immunophenotyping analysis moreover future prospective studies investigate longterm impact continuous eid terms clinical outcomes patient safetyif promising durable effect cd20 depletion confirmed ocrelizumab greater utility treatment ms due relatively low side effects limited need monitoring compared highly effective therapies however even ocrelizumab requires repeated treatments lower dosing frequency beneficial lessens likelihood infusionrelated events development severe infections,0.0
experiencia en la unidad de enfermedades desmielinizantes 2 aos multiple sclerosis chronic demyelinating disease causes progressive disability treatment focuses slowing progression preventing relapses effectively reducing symptoms conducted observational descriptive longitudinal singlecenter study patients admitted demyelinating diseases unit december 2017 february 2020 total number patients 625 received treatment ocrelizumab completed 12month followup without disease progression study highlight importance effectiveness diseasemodifying treatmentskeywords demielinating diseases multiple sclerosis ocrelizumab remitingrelapsing multiple sclerosis primary progressive multiple sclerosis,1.0
anatomical functional visual network patterns progressive multiple sclerosis hum brain mapp 2021 dec 20 doi 101002 hbm25744 online ahead printabstractthe gradual accrual disability time progressive multiple sclerosis believed driven widespread degeneration yet another facet problem may reside loss brains ability adapt damage incurred disease progresses study attempted examine whether changes associated optic neuritis structural functional visual networks can still discerned progressive patients even years acute insult fortyeight progressive multiple sclerosis patients 21 27 without prior optic neuritis underwent structural functional mri including dti resting state fmri anatomical functional visual networks analyzed using graph theorybased methods functional metrics significantly different two groups anatomical global efficiency density significantly lower optic neuritis group despite significant difference lesion load groups conclude longstanding distal damage optic nerve causes transsynaptic effects early ability cortex adapt may altered possibly nullified suggest limited ability brain compensate considered attempting explain accumulation disability progressive multiple sclerosis patientspmid34931352 doi101002 hbm25744,0.0
upper urinary tract function patients multiple sclerosis neurourol urodyn 2021 dec 21 doi 101002 nau24860 online ahead printabstractbackground neurogenic lower urinary tract dysfunction nlutd frequent multiple sclerosis ms renal prognosis key point bladder managementobjective assess upper urinary tract damage risk using voiding cystourethrography vcug patients pwms nlutdmethods conducted retrospective study 2010 2020 demographic data urinary symptoms urinary tract infection uti renal ultrasounds findings glomerular filtration rate gfr vcug data urodynamic parameters collected pwms nlutdresults among 325 pwms included 67 female mean age 516 120 years mean edss 46 18 vcug showed vesicoureteral reflux vur 18 patients link found vur progressive ms course p 004 hydronephrosis odds ratio 1744 95 confidence interval ci 3468787 p 0001 low gfr p 0001 detrusor overactivity p 004 association utis edss detrusor sphincter dyssynergia elicited multivariate analysis alteration gfr independently related presence vur 095 95 ci 092098 conclusions vur elicited vcug associated lower gfr hydronephrosis however due low prevalence 55 abnormality pwms vcug performed selected cases routinary practicepmid34931344 doi101002 nau24860,0.0
quality life disability clinical variables amyotrophic lateral sclerosis arq neuropsiquiatr 2021 dec 17s0004282x2021005028205 doi 101590 0004282xanp20210201 online ahead printabstractbackground amyotrophic lateral sclerosis als motor neuron disease results progressive increase dysfunctions limitations restrictions time can impact quality life qol therefore expanding knowledge qol possible factors associated als can enable development actions ensure greater wellbeing populationobjective investigate qol als determine associations demographic functional clinical aspectsmethods fortyfive individuals als 564111 years participated study demographic clinical functional aspects investigated functioning qol assessed using diseasespecific tools als functional ranting scalerevised alsfrsr als assessment questionnaire alsaq40 fatigue assessed using fatigue severity scale descriptive correlation stepwise multiple linear regression analyses performed aid spssresults mean alsaq40 score 27901183 qol significantly worse among women p0001 poor qol associated inability walk p0014 pain p0021 disease severity p0002 qol strongly correlated alsfrsr score r082 moderate weak correlations found mobility turning bed r062 locomotion r033 sit stand r040 strength r049 fatigue r035 pain r032 p003 regression analysis revealed alsfrsr score 076 p000 fatigue 020 p004 predictors qolconclusions qol worse women older people severe stages als patients impaired mobility poorer physical performance reported pain functional status fatigue predictors qol alspmid34932653 doi101590 0004282xanp20210201,0.0
frailty multiple sclerosis closer look deficit accumulation framework mult scler 2021 dec 2113524585211061332 doi 101177 13524585211061332 online ahead printno abstractpmid34931916 doi101177 13524585211061332,0.0
natalizumab concentrations pregnancy three patients multiple sclerosis mult scler 2021 dec 2113524585211052168 doi 101177 13524585211052168 online ahead printabstractin women active multiple sclerosis ms natalizumab can continued pregnancy prevent rebound disease activity aim evaluate changes serum natalizumab trough concentrations pregnancy blood samples 3 patients collected pregnancy natalizumab trough concentrations gradually decreased pregnancy patient lowest trough concentrations third trimester treated extended interval dosing eid delivery natalizumab concentrations increased similar levels pregnancy patients remained clinically radiologically stable ms neurologists aware decreasing natalizumab concentrations pregnancy especially patients low initial trough concentrations patients eidpmid34931887 doi101177 13524585211052168,0.0
evaluation upper extremity ataxia image processing individuals multiple sclerosis arq neuropsiquiatr 2021 dec 17s0004282x2021005027206 doi 101590 0004282xanp20200587 online ahead printabstractbackground impaired dexterity frequently reported disability among people ataxic multiple sclerosis ms objective quantify standardize evaluation upper extremity coordination disorder among patients multiple sclerosis ms using tablet ataxia assessment program taap methods x y axis movements 50 ms patients 30 healthy individuals evaluated using international cooperative ataxia rating scale icars also assessed using taap functional times participants right left hands recorded using ninehole peg test nhpt upper extremity coordination individuals ms evaluated using upper extremity kinetic functions section icarsresults deviations x y axis movements ms group greater control group p005 significant correlations shown taap scores nhpt icars scores strongest correlation found nhpt icars dominant hand rnhpt0356 pnhpt0001 ricars0439 picars0000 correlating y axis icars deviations y axis found greater nondominant hand x axis ryright0402 pyright0004 ryleft0691 pyleft0000 conclusion measurement using taap sensitive classical current methods evaluating ataxia think taap objective tool will allow neurorehabilitation professionals clinicians evaluate upper extremity coordinationpmid34932643 doi101590 0004282xanp20200587,0.0
correction adultonset vanishing white matter patient eif2b3 variants misdiagnosed multiple sclerosis neurol sci 2021 dec 21 doi 101007 s10072021057671 online ahead printno abstractpmid34932162 doi101007 s10072021057671,0.0
cerebellar dysfunction multiple sclerosis considerations research rehabilitation therapy neurorehabil neural repair 2021 dec 2115459683211065442 doi 101177 15459683211065442 online ahead printabstractintroduction cerebellar pathology common among persons multiple sclerosis pwms cerebellum well recognized role motor control motor learning cerebellar pathology multiple sclerosis associated enhanced motor impairment disability progression problem mitigate motor disability progression pwms commonly prescribed exercise taskspecific rehabilitation training yet whether cerebellar dysfunction differentially affects rehabilitation outcomes population remains unknown furthermore lack rehabilitation interventions targeting cerebellar dysfunction solution summarize current understanding impact cerebellar dysfunction motor control motor training rehabilitation persons multiple sclerosis recommendations additionally highlight critical knowledge gaps propose guide future research studying cerebellar dysfunction persons multiple sclerosispmid34931569 doi101177 15459683211065442,0.0
acute disseminated encephalomyelitis zh nevrol psikhiatr im s s korsakova 2021 121 11 119128 doi 1017116 jnevro2021121111119abstractacute disseminated encephalomyelitis aem immunemediated inflammatory demyelinating disease central nervous system cns usually singlephase wrem multiple lesions central nervous system inflammatorydemyelinating nature accompanied extremely polymorphic neurological disorders develop acutely subacutely review considers issues epidemiology trigger factors inflammatory process clinical manifestations differential molecular diagnostics wecm outlines ways study pathologypmid34932297 doi1017116 jnevro2021121111119,1.0
postvaccine covid19 patients multiple sclerosis neuromyelitis optica mult scler 2021 dec 2113524585211049737 doi 101177 13524585211049737 online ahead printabstractintroduction recent studies suggested anticd20 fingolimod may associated lower antispike proteinbased immunoglobuling response following covid19 vaccination evaluated covid19 occurred despite vaccination among patients multiple sclerosis ms neuromyelitis optica nmo using covisep registrycase series report 18 cases covid19 two doses bnt162b2vaccination 13 treated anticd20 four fingolimod covid19 severity milddiscussion results reinforce recommendation third covid19 vaccine dose among anticd20 treated patients stress need prospective clinical biological study covid19 vaccine efficacy among ms nmo patientspmid34931885 doi101177 13524585211049737,0.0
realworld patient characteristics treatment patterns costs relapsing multiple sclerosis patients treated glatiramer acetate dimethyl fumarate teriflunomide germany neurodegener dis manag 2021 dec 21 doi 102217 nmt20210031 online ahead printabstractaim evaluate adherence healthcare resource utilization hru costs glatiramer acetate ga injectable dimethyl fumarate oral teriflunomide oral relapsing multiple sclerosis patients methods retrospective analyses claims database results teriflunomide patients older comorbidities fewer relapses versus ga dimethyl fumarate ga patients mostly diseasemodifying therapies dmts treatment naive treatment adherence 6170 dmts reduced hru versus preindex costs comparable across cohorts high adherence reduced hospitalizations several costs versus low adherers conclusion adherence rates high comparable dmts similar high reductions hru costs occurred dmts high adherence improved economic outcomes versus low adherence thus investing adherence improvement beneficial improve outcomes relapsing multiple sclerosispmid34931528 doi102217 nmt20210031,0.0
genetically modified large animal models investigating neurodegenerative diseases abstractneurodegenerative diseases represent large group neurological disorders including alzheimers disease amyotrophic lateral sclerosis parkinsons disease huntingtons disease although group diseases show heterogeneous clinical pathological phenotypes share important pathological features characterized agedependent progressive degeneration nerve cells caused accumulation misfolded proteins association genetic mutations neurodegeneration diseases enabled establishment various types animal models mimic genetic defects provided important insights pathogenesis however genetically modified rodent models lack overt selective neurodegeneration seen patient brains making difficult use small animal models validate effective treatment neurodegeneration recent studies pig monkey models suggest large animals can faithfully recapitulate pathological features neurodegenerative diseases review discuss important differences animal models modeling pathological features neurodegenerative diseases aiming assist use animal models better understand pathogenesis develop effective therapeutic strategies,0.0
appearance claudin5+ leukocyte subtypes blood cns progression eae background tight junctions tjs membrane specializations characteristic barrierforming membranes function seal aqueous pathway endothelial cells epithelial cells thereby obstruct intercellular solute cellular movement however previous work laboratory found claudin5 cln5 tj protein prominent bloodbrain barrier bbb also detected ectopically leukocytes cln5+ blood central nervous system cns mice experimental autoimmune encephalomyelitis eae neuroinflammatory demyelinating disease model multiple sclerosis cln5 shown transferred endothelial cells circulating leukocytes disease prompting consideration action coupled leukocyte transendothelial migration tem cns fostering transient interactions corresponding leukocyte endothelial junctional proteins bbbmethodsto begin clarifying significance cln5+ leukocytes flow cytometry used determine appearance blood cns eaeresultsflow cytometric analysis revealed cln5+ populations among cd4 cd8 t cells b cells monocytes neutrophils appeared varying kinetics different extents blood cns cln5 levels circulating t cells correlated highly activation state percentage cln5+ cells among subtypes analyzed considerably higher cns tissue blood consistent interpretation cln5+ leukocytes gain preferred access cnsconclusionseveral leukocyte subtypes variably acquire cln5 blood enter cns event may represent novel mechanism guide leukocytes sites paracellular diapedesis across bbb,1.0
clinical tests predicting fallers among ambulatory patients amyotrophic lateral sclerosis preliminary cohort study j neuromuscul dis 2021 dec 12 doi 103233 jnd210730 online ahead printabstractbackground studies examined falls predictors patients amyotrophic lateral sclerosis als objective aim study survey fall incidence identify variables predicting presence absence falls occurring within 3 months discharge patients als hospitalmethods following variables evaluated 14 patients als timed go test tug functional reach test 10m comfortable gait speed singleleg stance time manual muscle test mmt scores lower limb total modified ashworth scale score lower limbs fear falling pull test score primary outcome variable occurrence fall within 3 months discharge fall rate calculated based fall record forms specific circumstances fall also recorded univariate multiple regression analyses used identify fall predictorsresults seven 14 als patients 50 experienced fall within 3 months five fallers reported experiencing fall caused injury three reported experiencing fall required hospital visit univariate logistic regression analysis identified tug time gait speed mmt ankle dorsiflexors factors associated falls p 002004 multiple linear regression analysis fall numbers identified age tug time predictor models p 003 conclusion tug time mmt ankle dorsiflexors may help predict falls als patients validation studies larger cohorts neededpmid34924399 doi103233 jnd210730,0.0
diffusely abnormal white matter converts t2 lesion volume absence mridetectable acute inflammation brain 2021 dec 20awab448 doi 101093 brain awab448 online ahead printabstractdiffusely abnormal white matter dawm characterised biochemical changes myelin absence frank demyelination associated clinical progression secondary progressive ms spms however little known changes dawm time relation focal white matter lesions fwml objectives work 1 characterize longitudinal evolution fwml dawm dawm transforms fwml 2 determine whether gadolinium enhancement known associated development new fwml also related dawm voxels transform fwml data included 4220 mri scans 689 spms participants followed 156 weeks 2677 scans 686 rrms participants followed 96 weeks fwml dawm segmented using previously validated automatic thresholding technique based normalized t2 intensity values using longitudinally registered images dawm voxels visit transformed fwml last mri scan well overlap gadolinium enhancing lesion masks identified results showed average yearly rate conversion dawmtofwml 127 cc spms 080 cc rrms fwml spms participants significantly increased t 39 p 00001 dawm significantly decreased t 43 p 00001 ratio fwmldawm increased t 127 p 000001 rrms participants also showed increase fwmldawm ratio t 69 p 000001 without significant change individual volumes gadolinium enhancement associated 73 187 focal new t2 lesion formation infrequent scans rrms spms cohorts respectively comparison 01 00 dawmtofwml voxels overlapped gadolinium enhancement conclude dawm transforms fwml time rrms spms dawm appears represent form prelesional pathology contributes t2 lesion volume increase time independent new focal inflammation gadolinium enhancementpmid34927199 doi101093 brain awab448,1.0
determining best window bnt162b2 mrna vaccination sarscov2 patients multiple sclerosis receiving anticd20 therapy mult scler j exp transl clin 2021 nov 29 7 4 20552173211062142 doi 101177 20552173211062142 ecollection 2021 octabstractwe studied serologic response bnt162b2 mrna vaccine four weeks second dose patients rrms treated rituximab extendedinterval dosing n 26 four weeks 73 patients seropositive patient without b cells first dose n 4 seropositive four seven 57 patients bcell proportion 0 5 seropositive patients bcell proportion 5 n 15 seropositive patients quantitative elisa measures vaccination correlated bcell counts measured vaccination patients receiving rituximab seropositivity bnt162b2 mrna vaccination emerged bcell repopulationpmid34925877 pmcpmc8673883 doi101177 20552173211062142,0.0
clinical features outcomes covid19 despite sarscov2 vaccination people multiple sclerosis mult scler j exp transl clin 2021 nov 26 7 4 20552173211057110 doi 101177 20552173211057110 ecollection 2021 octabstractbackground several studies demonstrated reduced serological response vaccines patients treated anticd20 agents however limited data exist surrounding clinical effect disease modifying therapy dmt use vaccine efficacyobjectives investigate breakthrough coronavirus disease 2019 covid19 vaccinated people multiple sclerosis pwms dmtmethods pwms dmt diagnosed covid19 full vaccination identified existing cleveland clinic covid19 registry supplemented provideridentified cases demographics disease history dmts comorbidities exposures vaccination status covid19 outcomes confirmed review electronic medical recordresults thirteen 38 344 fully vaccinated people multiple sclerosis disease modifying therapy diagnosed covid19 vaccination ten patients 769 anticd20 therapy remaining 3 231 fingolimod 2 patients 154 anticd20 therapy required hospitalization steroid treatment neither required intensive care unit admissionconclusion patients treated anticd20 agents sphingosine 1phosphate receptor modulators may still risk covid19 despite vaccination still risk hospitalization intubation death covid19 appear rare larger studies analyzing may differ setting emerging variants neededpmid34925875 pmcpmc8673876 doi101177 20552173211057110,0.0
longterm efficacy safety three times weekly dosing regimen glatiramer acetate relapsing multiple sclerosis patients sevenyear results glatiramer acetate lowfrequency administration gala openlabel extension study mult scler j exp transl clin 2021 dec 13 7 4 20552173211061550 doi 101177 20552173211061550 ecollection 2021 octabstractobjective describe longterm outcomes earlystart es delayedstart ds glatiramer acetate 40 mg ml treatment three times weekly ga40 seven years glatiramer acetate lowfrequency administration gala study patients relapsing multiple sclerosis rms methods patients evaluated every three six months primary efficacy endpoint annualized relapse rate arr additional endpoints exploratory post hoc efficacy data entire exposure period used es ds cohorts safety exposure ga40 consideredresults patients continued openlabel extension ole 580 834 70 es 261 419 62 ds completed ole entire placebocontrolled ole study period arr 026 es 031 ds patients risk ratio 083 95 confidence interval ci 070099 es prolonged median time first relapse versus ds 49 versus 43 years hazard ratio 082 95 ci 06096 oleonly results showed ds patients experienced similar efficacy relapse disability outcomes es patients adverse events consistent wellestablished ga safety profileconclusions ga40 treatment conferred clinical benefit seven years resulting sustained efficacy generally well tolerated rms patientspmid34925876 pmcpmc8671685 doi101177 20552173211061550,0.0
immune gene network neurological diseases multiple sclerosis ms alzheimer#39 s disease ad parkinson#39 s disease pd huntington#39 s disease hd heliyon 2021 dec 1 7 12 e08518 doi 101016 jheliyon2021e08518 ecollection 2021 decabstractneurological diseases ms ad pd hd major health concern elderly population still therapeutic options limited recent advances genomic sequencing bioinformatics present opportunity understand mechanisms diseases identification therapeutic targets several studies shown association immune dysfunction immune system mediated neurological disease ms well neurodegenerative diseases ad pd hd however similarities differences role immune system immune pathways immune cell types diseases remains unknown study immune cell type signature genes gene networks associated neurological diseases ms ad pd hd investigated using metaanalysis bioinformatics methods application weighted gene coexpression network analysis wgcna publicly available gene expression datasets microarray rnaseq revealed modarray_04 module microarray modrnaseq_06 module rnaseq significantly associated ms ad pd hd hypergeometric enrichment test revealed significant enrichment immune cell type genes neurological disease modules study demonstrates immune system mediated neurological disease ms neurodegenerative diseases ad pd hd share common gene network characterized immune cell type signature genes microglia monocytes macrophages probable targets therapeutic intervention summary work shows connection ms disease role immune system inflammation established neurodegenerative diseases ad pd hd role inflammation still hypothesispmid34926857 pmcpmc8649734 doi101016 jheliyon2021e08518,0.0
curcumin betadglucuronide modulates autoimmune model multiple sclerosis altered gut microbiota ileum feces front cell infect microbiol 2021 dec 3 11772962 doi 103389 fcimb2021772962 ecollection 2021abstractwe developed prodrug type curcumin curcumin monoglucuronide cmg whose intravenous intraperitoneal injection achieves high serum concentration freeform curcumin although curcumin reported alter gut microbiota immune responses unclear whether altered microbiota associated inflammation immunemediated diseases multiple sclerosis ms aimed determine whether cmg administration affect gut microbiota three anatomical sites feces ileal contents ileal mucosa leading suppression inflammation central nervous system cns autoimmune model ms experimental autoimmune encephalomyelitis eae injected eae mice cmg harvested brains spinal cords histological analyses conducted microbiome analyses using 16s rrna sequencing cmg administration modulated eae clinically histologically altered overall microbiota compositions feces ileal contents ileal mucosa principal component analysis pca microbiome showed principal component pc 1 values ileal contents feces correlated clinical histological eae scores hand analyzed individual bacteria microbiota eae scores correlated significant increases relative abundance two bacterial species anatomical site ruminococcus bromii blautia ruminococcus gnavus feces turicibacter sp alistipes finegoldii ileal contents burkholderia spp azoarcus spp ileal mucosa therefore cmg administration alter gut microbiota three different sites differentially overall gut microbiome compositions also abundance individual bacteria associated modulation neuroinflammationpmid34926318 pmcpmc8677657 doi103389 fcimb2021772962,0.0
t1 relaxation times cortex thalamus associated working memory information processing speed patients multiple sclerosis front neurol 2021 dec 3 12789812 doi 103389 fneur2021789812 ecollection 2021abstractbackground cortical thalamic pathologies associated cognitive impairment patients multiple sclerosis ms objective aimed quantify cortical thalamic damage patients ms using highresolution t1 mapping technique evaluate association changes clinical cognitive impairment methods study group consisted 49 patients mainly relapsingremitting ms 17 agematched healthy controls received 3t mris including t1 mapping sequence mp2rage mean t1 relaxation times t1rt cortex thalami compared patients ms healthy controls additionally correlation analysis performed assess relationship mri parameters clinical cognitive disability results patients ms significantly decreased normalized brain gray matter white matter volumes well increased t1rt normalappearing white matter compared healthy controls p 0001 partial correlation analysis age sex disease duration covariates revealed correlations t1rt cortex r 033 p 005 thalami right thalamus r 037 left thalamus r 050 p 005 working memory information processing speed measured symboldigit modalities test conclusion t1rt cortex thalamus correlate information processing speed patients mspmid34925222 pmcpmc8678069 doi103389 fneur2021789812,0.0
quantitative susceptibility mappingderived radiomic features discriminating multiple sclerosis neuromyelitis optica spectrum disorder front neurosci 2021 dec 3 15765634 doi 103389 fnins2021765634 ecollection 2021abstractobjectives implement machine learning model using radiomic features extracted quantitative susceptibility mapping qsm discriminating multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd materials methods fortyseven patients ms mean age 4000 1372 years 36 patients nmosd mean age 4214 1234 years underwent enhanced gradientecho t2weighted angiography eswan sequence 30t mri included april 2017 october 2019 qsm images reconstructed eswan qsmderived radiomic features obtained seven regions interest rois including bilateral putamen globus pallidus head caudate nucleus thalamus substantia nigra red nucleus dentate nucleus machine learning model logistic regression applied classify ms nmosd combined radiomic signatures demographic information assess classification accuracy using area receiver operating characteristic roc curve auc results radiomicsonly models showed better discrimination performance almost deep gray matter dgm regions demographic informationonly model highest auc dn 0902 95 ci 08400955 moreover hybrid model combining radiomic signatures demographic information showed highest discrimination performance achieved auc 0927 95 ci 08710984 fivefold crossvalidation conclusion hybrid model based qsm powered machine learning potential discriminate ms nmosdpmid34924934 pmcpmc8678528 doi103389 fnins2021765634,0.0
toxic heavy metal concentrations multiple sclerosis patients systematic review metaanalysis excli j 2021 nov 19 2015711584 doi 1017179 excli20213484 ecollection 2021abstractthe present metaanalysis performed assess association ms patients control subjects terms circulating levels arsenic lead pb mercury hg cadmium cd searched medline pubmed scopus web science embase june 2020 identify studies examined concentrations heavy metals ms patients statistical tests used assess interstudy heterogeneity cochranes q test i2 statistic given observed significant heterogeneity randomeffects model employed pool weighted mean differences wmds corresponding 95 confidence intervals cis total 1181 articles 16 studies 1650 participants 772 patients ms 878 controls included review metaanalysis pooled results using randomeffects model showed levels pb wmd 073 g l 95 ci 033 112 p 0001 wmd 248 g l 95 ci 144 353 p 0001 i2 989 p 0001 cd wmd 017 g l 95 ci 009 026 p 0001 significantly higher ms patients controls however significant differences levels hg wmd 014 g l 95 ci 077 049 p 0658 among groups sensitivity analysis indicated excluding onebyone study overall pooled wmd pb changed metaanalysis showed patients ms significantly higher levels circulatory cd compared controls yet statistically significant difference circulating levels hg pb among ms patients controls see also figure 1 fig 1 pmid34924905 pmcpmc8678057 doi1017179 excli20213484,0.0
spectrum clinical presentation multiple sclerosis neuromyelitis optica spectrum disorder young patients community cureus 2021 nov 14 13 11 e19576 doi 107759 cureus19576 ecollection 2021 novabstractbackground neuromyelitis optica spectrum disorder nmosd inflammatory demyelinating syndrome central nervous system cns affects spinal cord optic nerves aim study evaluate clinical appearance multiple sclerosis neuromyelitis optica spectrum disease young children community materials methods crosssectional study done neurology departments combined military hospital pak emirates military hospital rawalpindi six months april 2020 september 2020 eighty people ages 18 45 guillainbarre syndrome gbs multiple sclerosis ms neuromyelitis optica spectrum disorder participated prospective research patients demographic profile includes information age gender length kind sickness symptoms relationship sociodemographic factors assessed involvement one organ system time presentation results final study comprised 80 patients 31 385 percent men 49 6125 women fiftyfour 675 patients diagnosed multiple sclerosis 26 325 neuromyelitis optica spectrum disorders patients presented sensory symptoms followed visual disturbances twentynine 37 involvement one system 51 63 involvement one system time presentation female gender diagnosis multiple sclerosis statistically significant relationship involvement one one system conclusions individuals ms nmo motor sensory visual symptoms often observed time presentation involvement one one system time presentation fairly common among patients females patients diagnosis multiple sclerosis risk involvement one systempmid34926048 pmcpmc8671079 doi107759 cureus19576,1.0
phosphorylated neurofilament heavy chain pnfh clinically isolated syndrome multiple sclerosis noro psikiyatr ars 2021 nov 15 58 4 255256 doi 1029399 npa28019 ecollection 2021no abstractpmid34924782 pmcpmc8665293 doi1029399 npa28019,0.0
late onset psychotic depression multiple sclerosis case report psychiatr danub 2021 winter 33 4 574577 doi 1024869 psyd2021574no abstractpmid34928908 doi1024869 psyd2021574,0.0
female sexual function body image urinary diversion benign conditions j sex med 2021 dec 16s17436095 21 007839 doi 101016 jjsxm202111007 online ahead printabstractbackground simple cystectomy urinary diversion favored option treating conditions responsible neurogenic bladder dysfunction failure conservative treatments despite existence validated assessment tools impact cystectomy female sexual function remains scarcely investigatedaim aim assess sexual function body image female patients underwent urinary diversion nonmalignant condition investigate factors may influence sexual life qualitymethods 36 female patients underwent urinary diversion cystectomy benign condition january 1 2007 december 15 2019 included standardized questionnaires sent mail february april 2021 additional data collected patient computerized medical recordsoutcomes female sexual function index fsfi body image scale bis stoma quality life stomaqol questionnaires used assess sexual activity body image quality life related noncontinent stoma respectively quality pre postoperative information also assessedresults frequent etiology bladder dysfunction multiple sclerosis 14 389 surgery 29 806 patients sexually active mean range overall fsfi score 152 2333 mean range overall fsfi score fsfi arousal subscore lower 14 patients ileal conduit 111 2333 1 045 compared 14 patients continent stoma native urethra 192 2293 p 04 315 054 p 014 regarding sexual counseling 27 794 patients receive information surgery possible consequences sexual activity 31 912 asked sexual activity followup mean bis score higher patients ileal conduit 148 compared patients continent stoma 97 native urethra 51 p 002 patients ileal conduit mean stomaqol score 5256clinical implications optimal management include least routine assessment sexual function prior simple cystectomy screening sexual dysfunction followup strengths limitations main strength study lies use validated standardized questionnaires including fsfi considered relevant tool assessing female sexual function limitations include small number patients potential memory biasconclusion present study suggests urinary diversion mode impact sexual function body image cystectomy benign condition l margaux mj nicolas r alain et al female sexual function body image urinary diversion benign conditions j sex med 2021 xxxxxxxxpmid34924334 doi101016 jjsxm202111007,0.0
adequate antibody response biontech covid vaccine multiple sclerosis patient treated siponimod egypt j neurol psychiatr neurosurg 2021 57 1 171 doi 101186 s41983021004288 epub 2021 dec 14no abstractpmid34924749 pmcpmc8669414 doi101186 s41983021004288,0.0
minocycline mitigation tremor syndrome defect cognitive balance induced harmaline basic clin neurosci 2021 marapr 12 2 255268 doi 1032598 bcn12219801 epub 2021 mar 1abstractintroduction minocycline antiinflammatory antiapoptotic antioxidant effects preclinical data suggest minocycline beneficial treating common neurological disorders including parkinson disease multiple sclerosismethods study effects minocycline harmalineinduced motor cognitive impairments studied male wistar rats rats divided four groups ten animals harmaline used induction essential tremor et minocycline 90 mg kg ip administered 30 minutes saline harmaline tremor intensity spontaneous locomotor activity passive avoidance memory anxietyrelated behaviors motor function assessed ratsresults results showed minocycline recover tremor intensity step width failed recuperate motor balance memory impairments observed harmalinetreated rats somewhat reversed administration minocycline cerebellum inferior olive nucleus studied neuronal degeneration using histochemistry transmission electron microscopy techniques harmaline caused ultrastructural changes neuronal cell loss inferior olive cerebellar purkinje cells minocycline exhibited neuroprotective changes cerebellar purkinje cells inferior olivary neuronsconclusion results open new therapeutic perspectives motor memory impairments et however studies needed clarify exact mechanismspmid34925722 pmcpmc8672663 doi1032598 bcn12219801,1.0
evolution blood flow restricted exercise front physiol 2021 dec 2 12747759 doi 103389 fphys2021747759 ecollection 2021abstractthe use blood flow restricted bfr exercise become accepted alternative approach improve skeletal muscle mass function improve cardiovascular function individuals able wish use traditional exercise protocols rely heavy loads high training volumes bfr exercise involves reduction blood flow working skeletal muscle applying flexible cuff proximal portions persons arms legs results decreased arterial flow exercising muscle occluded venous return back central circulation safety concerns especially related cardiovascular system consistently reported exceptions however researchers agree bfr exercise can relatively safe technique people free serious cardiovascular disease well coronary artery disease also people suffering chronic conditions multiple sclerosis parkinsons osteoarthritis potential mechanisms explain benefits bfr exercise still mostly speculative may require invasive studies use animal models fully explore mechanisms adaptation setting absolute resistive pressures evolved based individuals systolic blood pressure relative measure based various percentages pressures needed totally occlude blood flow exercising limb however since several issues remain unresolved actual external loads used combination bfr type cuff used induce blood flow restriction whether restriction continuous intermittent paper will attempt address additional concernspmid34925056 pmcpmc8674694 doi103389 fphys2021747759,0.0
safety efficacy fingolimod iranian patients relapsingremitting multiple sclerosis basic clin neurosci 2021 marapr 12 2 233242 doi 1032598 bcn12216811 epub 2021 mar 1abstractintroduction fingolimod first confirmed oral immunemodulator treat relapsingremitting multiple sclerosis rrms study aimed investigate safety efficacy fingolimod therapy iranian patients rrmsmethods trial 50 patients resistant conventional interferon therapy assigned receive fingolimod 05 mg per day 12 months number dadolinium gd enhanced lesions enlarged t2 lesions relapses 12 months considered endpoints compared baseline liver biochemical evaluations lymphocyte count done baseline months 3 6 12 study patients also monitored possible cardiovascular events within first 24 h side effects routinelyresults among patients completed trial number gdenhanced enlarged t2 lesions 12 months significantly decreased p003 p0001 respectively proportion relapsefree patients higher compared onset fingolimod administration significant alterations expanded disability status scale edss scores slight transient increase recorded liver enzymes among participants lymphocyte count reduced 61 month 1 displayed gradual increase month 12 bradycardia macular edema recordedconclusion findings indicate effective firstline fingolimod therapy first time iranian patients rrms decrease number new attacks amelioration mri lesions benefits fingolimod therapy suggesting preferred medicines treat rrms iranpmid34925720 pmcpmc8672667 doi1032598 bcn12216811,0.0
dynamic topology analysis spatial patterns multifocal lesions mri med image anal 2021 oct 29 76102267 doi 101016 jmedia2021102267 online ahead printabstractquantitatively analysing spatial patterns multifocal lesions clinical mri important step towards better understanding disease precision medicine yet properly explored feature engineering deep learning methods network science addresses issue explicitly modeling interlesion topology however construction informative graph optimal edge sparsity quantification community graph structures current challenges network science paper address challenges novel dynamic topology analysis framework basis persistent homology aiming investigate predictive values global geometry local clusters multifocal lesions firstly dynamic hierarchical network proposed construct informative global communitylevel topology multiscale networks sparse dense multiscale global topology constructed nested sequence rips complexes new ksimplex filtration designed generate higherlevel topological abstraction community identification based connectivity ksimplices rips complex secondly quantify multiscale community structures design new decomposed community persistence algorithm track dynamic evolution communities summarise evolutionary communities incorporated customisable descriptor quantified community features encapsulated global geometric invariants topological pattern analysis proposed framework evaluated diagnostic differentiation prognostic prediction multiple sclerosis typical multifocal disease achieved roc_auc 0875 0767 respectively outperforming seven stateoftheart persistent homology methods reported performance six feature engineering deep learning methodspmid34929461 doi101016 jmedia2021102267,0.0
study ergocalciferol cholecalciferol vitamin d modeled optical properties optical detection using absorption raman spectroscopy spectrochim acta mol biomol spectrosc 2021 dec 10 269120725 doi 101016 jsaa2021120725 online ahead printabstractthe task assembling calculating spectrally significant lines vitamin d2 d3 related wider goal establishing possible develop noninvasive optical sensors substances present concentrations order tens nmol l noninvasive vivo sensor helpful medical considerations among others related multiple sclerosis prevention reduced risk mortality d3treated acute inpatients admitted covid 19 systemic infection acute respiratory tract infections including epidemic influenza communityacquired pneumonia concentrations 50nmol l 20ng ml dental health 90100nmol l 25 oh d general health others currently determine concentration substances necessary draw sample vein ambulatory settings analyse sample gold standard mass spectroscopy immunoassay article vitamin d optical properties studied density functional theory calculations compared reported data new calculated measured d2 d3 optical absorption lines presented well calculations compared spectral measurements optical transmission ftir atr raman spectrapmid34929622 doi101016 jsaa2021120725,0.0
encapsulation bryostatin1 targeted exosomes enhances remyelination neuroprotection effects cuprizoneinduced demyelinating animal model multiple sclerosis biomater sci 2021 dec 20 doi 101039 d1bm01142a online ahead printabstractdemyelination critical neurological disease still lack effective treatment methods past two decades stem cells emerged novel therapeutic effector neural regeneration however owing existence bloodbrain barrier bbb complex microenvironment targeted therapy still faces multiple challenges targeted exosome carriers drug delivery may considered promising therapeutic method exosomes isolated mice neural stem cells develop targeting exosomes generated lentivirus armed pdgfr ligand anchor membrane exosome targeting tests carried vitro vivo modified exosomes showed apparent ability target opcs lesion area next exosomes loaded bryostatin1 bryo cuprizonefed mice administered targeting exosomes data show bryo exhibits powerful therapeutic effect compared bryo alone exosome encapsulation specifically novel exosomebased targeting delivery bryo significantly improves protection ability myelin sheath promotes remyelination moreover blocks astrogliosis axon damage also inhibitory effect proinflammatory microglia results investigation provide straightforward strategy produce targeting exosomes indicate potential therapeutic approach demyelinating diseasepmid34928285 doi101039 d1bm01142a,1.0
psychosis rare onset symptom pediatric multiple sclerosis neurocase 2021 dec 2013 doi 101080 1355479420212016859 online ahead printabstractneuropsychiatric symptoms common multiple sclerosis ms rarely associated psychosis initial manifestation fourteenyearold boy admitted auditory hallucinations neurological examination normal brain magnetic resonance imaging mri showed multiple demyelinating lesions mesencephalon periventricular regions igg index high oligoclonal band positive ms diagnosed pulsed corticosteroids given psychotic symptoms regressed 22months patient presented hemihypoesthesia repeated mri showed new contrast enhancing lesion detected complaints completely resolved pulse corticosteroid therapy increasing morbidity due delay ms treatment underlines need consider ms differential diagnosis pediatric cases presenting psychosispmid34927555 doi101080 1355479420212016859,1.0
early firstline treatment response subsequent disability worsening relapsingremitting ms eur j neurol 2021 dec 20 doi 101111 ene15220 online ahead printabstractbackground treatment success relapsingremitting ms rrms generally determined using relapse frequency mri activity first 6 12 months treatment association definitions shortterm treatment success disability worsening disease activity longerterm unclear study investigated risk factors associated early firstline treatment failure rrms association early treatment failure subsequent disability worsening evidence disease activity neda3 statusmethods used data combirx clinicaltrialsgov identifier nct00211887 investigate risk factors associated early treatment failure association early treatment failure 6 12 months subsequent disability worsening evidence disease activity neda3 36 monthsresults combirx included 1 008 treatmentnave participants rrms randomly assigned treatment glatiramer acetate interferon beta combination early treatment failure 6 12 months several definitions associated neda3 failure 36 months subsequent disability worsening 36 months edss baseline characteristic associated risk disability worsening 36 months around 70 neda3 failures occurred due mri activity less 10 due edss worseningconclusions investigation shows current definitions early treatment failure rrms unrelated patientrelevant disability worsening 36 months followup research useful definitions treatment success failure rrms neededpmid34927308 doi101111 ene15220,0.0
pysustain python implementation subtype stage inference algorithm softwarex 2021 dec 16100811 doi 101016 jsoftx2021100811 epub 2021 sep 25abstractprogressive disorders highly heterogeneous symptombased clinical classification disorders may reflect underlying pathobiology datadriven subtyping staging patients potential disentangle complex spatiotemporal patterns disease progression tools enable high demand clinical treatmentdevelopment communities describe pysustain software package pythonbased implementation subtype stage inference sustain algorithm sustain unravels complexity heterogeneous diseases inferring multiple disease progression patterns subtypes individual severity stages crosssectional data primary aims pysustain enable widespread application translation sustain via accessible python package supports simple extension generalization novel modelling situations within single consistent architecturepmid34926780 pmcpmc8682799 doi101016 jsoftx2021100811,0.0
engineering characterization biological evaluation antibody targeting hgf receptor front immunol 2021 dec 3 12775151 doi 103389 fimmu2021775151 ecollection 2021abstractthe hepatocyte growth factor hgf receptor met promote several physiological activities tissue regeneration protection cell injury epithelial endothelial neuronal muscle cells therapeutic potential met activation scrutinized treatment acute tissue injury chronic inflammation renal fibrosis multiple sclerosis ms cardiovascular neurodegenerative diseases hand hgfmet signaling pathway may caught cancer cells turned work invasion metastasis drug resistance tumor microenvironment engineered recombinant antibody rdo24 two derived fragments binding extracellular domain ecd met protein antibody binds high affinity 8 nm met ecd crossreact closely related receptors ron semaphorin 4d deletion mapping studies computational modeling show rdo24 binds structure bent plexinsemaphorinintegrin psi domain implicating psi domain binding met intact rdo24 antibody bivalent fab2 monovalent fab induce met autophosphorylation mimicking mechanism action hgf activates receptor dimerization accordingly bivalent recombinant molecules induce hgf biological responses cell migration wound healing behaving met agonists therapeutic interest regenerative medicine vivo administration rdo24 murine model ms represented experimental autoimmune encephalomyelitis eae delays eae onset mitigates early clinical symptoms reduces inflammatory infiltrates altogether results suggest engineered rdo24 antibody may beneficial multiple sclerosis possibly types inflammatory disorderspmid34925346 pmcpmc8679783 doi103389 fimmu2021775151,0.0
immunosenescence autoimmunity exploiting tcell receptor repertoire investigate impact aging multiple sclerosis front immunol 2021 dec 1 12799380 doi 103389 fimmu2021799380 ecollection 2021abstracttcell receptor tcr repertoire diversity determining factor immune system capability fighting infections preventing autoimmunity life tcr repertoire diversity progressively declines physiological aging progress investigation tcr repertoire dynamics life represents powerful tool unraveling impact immunosenescence health disease multiple sclerosis ms demyelinating inflammatory tcell mediated autoimmune disease central nervous system age crucial widespread neurological disease among young adults furthermore patients age may impact ms progression treatments outcome crossing knowledge tcr repertoire dynamics ms patients life fundamental investigate disease mechanisms advent high throughput sequencing hts significantly increased knowledge topic report overview current literature impact immunosenescence agerelated tcr dynamics variation autoimmunity including mspmid34925384 pmcpmc8673061 doi103389 fimmu2021799380,1.0
recent advances clinical trials targeting kynurenine pathway pharmacol ther 2021 dec 17108055 doi 101016 jpharmthera2021108055 online ahead printabstractthe kynurenine pathway kp major catabolic pathway essential amino acid tryptophan leading production nicotinamide adenine dinucleotide inflammatory conditions activation kp leads production several bioactive metabolites including kynurenine 3hydroxykynurenine 3hydroxyanthranilic acid kynurenic acid quinolinic acid metabolites can redox immune suppressive activity neurotoxic neuroprotective activity pathway tightly regulated normal physiological condition can upregulated immunological activation inflammation dysregulation kp implicated wide range neurological diseases psychiatric disorders review discuss mechanisms involved kpmediated neurotoxicity immune suppression role diseases expertise including cancer chronic pain multiple sclerosis also provide updates clinical trials evaluating efficacy kp inhibitors analogues respective diseasepmid34929198 doi101016 jpharmthera2021108055,1.0
vaccination opportunities multiple sclerosis patients treated cladribine tablets curr neuropharmacol 2021 dec 17 doi 102174 1570159x20666211217160451 online ahead printabstractthe covid19 pandemic mass vaccination campaign highlighted situation vulnerable patients work focused attention patients multiple sclerosis ms particularly treatment cladribine tablets trying understand possible administer vaccine successfully considering innovative topic reviewed existing literature analysis experiences also related vaccinations including influenza vzv recent data countries vaccination campaigns already advanced overall taken account mechanism action pharmacokinetic pharmacodynamic cladribine changes immune system administration together preliminary data humoral response influenza vzv sarscov2 vaccinations cladribine treated patients conclusion data showed use cladribine tablets seems permit flexibility regarding vaccination timing suggest vaccination patients safe effectivepmid34923946 doi102174 1570159x20666211217160451,0.0
inadequate vaccine responses children multiple sclerosis front pediatr 2021 dec 1 9790159 doi 103389 fped2021790159 ecollection 2021abstractobjective immunizations hepatitis b virus hbv varicella zoster virus vzv recommended patients pediatric onset multiple sclerosis poms may required prior initiation disease modifying therapies however efficacy routine vaccine administration poms never studied sought assess humoral mediated vaccine response hbv vzv children poms methods multicenter retrospective chartbased review 62 patients poms performed clinical data antibody titers hbv vzv collected prior initiation disease modifying therapy steroids compared institutional control data using ttest chi squared analysis results low rates immunity hbv vzv 33 25 respectively among individuals poms fifteen individuals 24 nonimmune compared institutional control data individuals poms significantly less likely immune hbv p 0003 95 ci 022075 vzv p 0001 95 ci 009039 interpretation individuals poms low rates antibodymediated immunity hbv vzv despite receiving appropriate vaccinations suggests association poms systemic immune dysregulation although study neededpmid34926358 pmcpmc8678906 doi103389 fped2021790159,0.0
alpha#x2f betahydrolase domaincontaining 6 signaling function central nervous system front pharmacol 2021 dec 2 12784202 doi 103389 fphar2021784202 ecollection 2021abstractendocannabinoid ecb signaling plays important role central nervous system cns hydrolase domaincontaining 6 abhd6 transmembrane serine hydrolase hydrolyzes monoacylglycerol mag lipids endocannabinoid 2arachidonoyl glycerol 2ag abhd6 participates neurotransmission inflammation brain energy metabolism tumorigenesis biological processes potential therapeutic target various neurological diseases traumatic brain injury tbi multiple sclerosis ms epilepsy mental illness pain review summarizes molecular mechanisms action biological functions abhd6 particularly mechanism action pathogenesis neurological diseases provides theoretical basis new pharmacological interventions via targeting abhd6pmid34925039 pmcpmc8675881 doi103389 fphar2021784202,0.0
socioeconomic disadvantage multiple sclerosis inequality act substrate disability brain 2021 dec 20awab424 doi 101093 brain awab424 online ahead printno abstractpmid34927667 doi101093 brain awab424,0.0
reference ranges t lymphocyte subsets singleplatform among healthy population southwest china background appropriate reference ranges t lymphocyte subsets essential immune status evaluation patients immunological diseases aim establish age sexrelated reference intervals t lymphocyte subsets singleplatform southwest china population using indirect method data resulting 53 822 cases periodic health examination individuals laboratory information system lis west china hospital 2018 2020methodswe used boxcox conversion combined tukey method normalize data eliminate outliers nonparametric method estimate 95 distribution reference intervalsresultswe initially established reference ranges t lymphocyte subsets singleplatform among healthy population southwest china indirect method see text details using standard normal deviate test ztest suggested harris boyd according clsi ep28a3c scientific found reference ranges t lymphocyte subsets differentiated ages genders since reference ranges t lymphocyte subsets singleplatform different ages genders significantly differentconclusionswe demonstrated absolute count cd3 + t cell cd3 + cd4 + t cell cd3 + cd8 + t cell decreased aging marked men cd3 + cd8 + t cell count obtained reference intervals superior reference intervals derived reagent specification currently use,0.0
tdp43 pathology alzheimers disease abstracttransactive response dna binding protein 43 kda tdp43 intranuclear protein encoded tardbp gene involved rna splicing trafficking stabilization thus regulation gene expression cytoplasmic inclusion bodies containing phosphorylated truncated forms tdp43 hallmarks amyotrophic lateral sclerosis als subset frontotemporal lobar degeneration ftld additionally tdp43 inclusions found 57 alzheimers disease ad cases often limbic distribution without hippocampal sclerosis cases tdp43 deposits also found neurons neurofibrillary tangles ad patients tdp43 pathology increased severity cognitive impairment compared without tdp43 pathology furthermore common genetic risk factor ad apolipoprotein e4 apoe4 associated increased frequency tdp43 pathology findings provide strong evidence tdp43 pathology integral part multiple neurodegenerative conditions including ad review biology pathobiology tdp43 focus role ad emphasize need studies mechanisms lead tdp43 pathology especially setting agerelated disorders ad,0.0
bullous pemphigoid diabetic patients treated gliptins side coin abstractbullous pemphigoid bp common autoimmune bullous skin disease affects primarily patients older 60 years majority bp cases spontaneous bp can also triggered certain drugs exposures since 2011 growing number observations reporting cases bp type 2 diabetic patients forms linked use new category antidiabetic drugs called dipeptidyl peptidase inhibitors dpp4i gliptins date exact pathophysiological mechanisms underlying association completely elucidated although conventional gliptinassociated bp thought share similar clinical histopathological features thorough review recent literature shows 2 forms quite distinct dpp4iassociated bp seems appear earlier age spontaneous bp may manifest either noninflammatory inflammatory phenotype conventional form presents typical inflammatory phenotype additionally important distinctive histological feature recently shown gliptinassociated bp forms may present less significant eosinophils infiltrate upper dermis periblister lesions compared skin patients spontaneous bp seems specific feature clinically noninflammatory forms accordance previous literature found direct immunofluorescence dif gives identical findings dpp4iassociated conventional forms bp igg complement c3 deposition linear band dermalepidermal junction perilesional skin indirect immunofluorescence shows presence igg circulating autoantibodies patients serum titer differ spontaneous dpp4iassociated bp specificity autoantibodies may different spontaneous induced noninflammatory induced inflammatory forms epitope spreading phenomenon seems play role determining specificities research based integrated epidemiological clinical histoimmunological pharmacogenomic approaches may give insight forms bp combined approach will allow better define bp endotypes unveil mechanism spontaneous druginduced breakage immunotolerance skin selfantigens,0.0
assessment antipd l 1 patients coexisting malignant tumor tuberculosis classified active latent obsolete stage background rare clinical scenario patients presenting coexisting malignant tumor tuberculosis whether feasible conduct programmed death ligand 1 pd l 1 inhibitors patients especially active tuberculosis treated concurrent antituberculosis still unknownmethodsthis study enrolled patients coexisting malignancy tuberculosis treated antipd l 1 jan 2018 july 2021 2 institutions progressionfree survival pfs objective response rate orr safety antipd l 1 therapy well response antituberculosis treatment evaluatedresultsa total 98 patients screened cohort study 45 459 21 214 32 327 patients diagnosed active latent obsolete tuberculosis respectively overall orr 360 antipd l 1 therapy 342 355 412 subgroup median pfs 80 vs 60 vs 60 months p0685 subgroup time analysis patients active tuberculosis treated concurrent antituberculosis median duration antituberculosis therapy 100 95 ci 8011199 months 833 20 24 933 42 45 patients showing sputum conversion radiographic response respectively antituberculosis therapy two patients experienced tuberculosis relapse notably none patients latent one patient obsolete subgroups showed tuberculosis induction relapse antipd l 1 therapy treatmentrelated adverse events traes occurred 33 patients 733 treated concurrent antipd l 1 antituberculosis grade 3 higher traes hematotoxicity n 5 111 one patient suffered grade 3 pneumonitis leading discontinuation immunotherapyconclusionsthis study demonstrated patients coexisting malignant tumor tuberculosis benefited equally antipd l 1 therapy antituberculosis response unimpaired active tuberculosis notably combination antipd l 1 antituberculosis therapy welltolerated without significant unexpected toxic effects,0.0
novel betaretrovirus discovered cattle neurological disease encephalitis background majority emerging infectious diseases humans animal origin many caused neuropathogenic viruses many cases neurological disease encephalitis livestock remain etiologically unresolved posing constant threat animal human health thus continuous extension knowledge repertoire viruses prone infect central nervous system cns vital pathogen monitoring early detection emerging viruses using highthroughput sequencing hts bioinformatics discovered new retrovirus bovine retrovirus ch15 borv ch15 cns cow nonsuppurative encephalitis phylogenetic analysis revealed affiliation borv ch15 genus betaretrovirusresultsborv ch15 genomes identified prospectively retrospectively pcr rtpcr hts targeting viral rna proviral dna six additional diseased cows investigated period 20 years different geographical origins virus found brain samples healthy slaughtered control animals n 130 determined fulllength proviral genomes six seven investigated animals using situ hybridization identified viral rna cytoplasm cells morphologically compatible neurons diseased brainsconclusionsfurther screening brain samples virus isolation infection studies needed estimate significance findings causative association borv ch15 neurological disease encephalitis cattle however fulllength proviral sequences borv ch15 genomes provide basis molecular clone vitro investigationgraphical abstract,0.0
rapidly progressive respiratory failure helminth larvae ingestion background selfadministration helminths gained attention among patients potential unproven therapy autoimmune disease present case rapidly progressive respiratory failure patient systemic sclerosis ssc pulmonary arterial hypertension pah result selfadministration parasitic organismscasea 45yearold woman history interstitial lung disease pah due limited cutaneous ssc presented pulmonary clinic worsening dyspnea cough new onset hypoxemia three months prior presentation started oral helminth therapy necator americanus alternative treatment ssc laboratory evaluation revelaed eosinophilia elevated ige levels igg antibodies strongyloides detected high resolution computed tomography chest revealed progressive ild new diffuse ground glass opacities transthoracic echocardiogram right heart catheterization illustrated worsening pah right heart failure patient admitted hospital emergently evaluated lung transplantation candidate transplantation due comorbidities despite aggressive treatment pah right heart failure respiratory status deteriorated patient transitioned comfortfocused careconclusionalthough ingestion helminths poses risk infection helminth therapy investigated potential treatment autoimmune diseases case selfprescribed helminth ingestion precipitated fatal acute worsening lung inflammation hypoxemia right heart dysfunction highlighting risk experimental helminth therapy patients especially underlying respiratory disease,0.0
targeting ck2 mediated signaling impair#x2f tackle sarscov2 infection computational biology approach background similarities hijacking mechanisms used sarscov2 several types cancer suggest repurposing cancer drugs treat covid19 ck2 kinase antagonists proposed cancer treatment recent study cells infected sarscov2 found significant ck2 kinase activity use ck2 inhibitor showed antiviral responses cigb300 originally designed anticancer peptide antagonist ck2 kinase activity binds ck2 phosphoacceptor sites recent preliminary results show antiviral activity cigb300 using surrogate model coronavirus present computational biology study provides evidence molecular level cigb300 may interfere sarscov2 life cycle within infected human cellsmethodssequence analyses data phosphorylation studies combined predict infectioninduced molecular mechanisms can interfered cigb300 next integrated data multiomics studies data focusing antagonistic effect ck2 kinase activity cigb300 combination network functional enrichment analyses usedresultsfirstly sarscov studies inferred potential incidence cigb300 sarscov2 interference immune response afterwards analysis multiple omics data proposed action cigb300 early stages viral infections perturbing virus hijacking rna splicing machinery also predicted interference cigb300 virushost interactions responsible high infectivity particular immune response sarscov2 infection furthermore provided evidence cigb300 may participate attenuation phenotypes related muscle bleeding coagulation respiratory disordersconclusionsour computational analysis proposes putative molecular mechanisms support antiviral activity cigb300,0.0
factors impacting cumulative dissipated energy levels postoperative visual acuity outcome cataract surgery abstractpurposeto determine factors impacting cumulative dissipated energy cde postoperative bestcorrected visual acuity bcva phacoemulsificationdesignreview 1102 cases university california san francisco ucsf zhongshan ophthalmic center zoc chinasubjectspatients underwent cataract surgery ucsf 03 201403 2019 zoc 10 201805 2019methodspatient demographics medical history routine ocular examination surgical information including disassembly method complications surgeon training level recorded univariable multivariable regression models used determine factors associated cde good postoperative bcva 20 40 better 1 monthoutcome measurescde postoperative bcvaresultsin multivariable analysis patient age time surgery diabetes degree nuclear sclerosis ns whitetowhite corneal diameter disassembly method preoperative bcva surgeon training level surgical center significantly associated cde log10cde increased 020031 patient age 70 years 007 patient diabetes 012041 ns grade 2 048 per 10 mm increase whitetowhite corneal diameter 034047 disassembly method nonstop chop 016 per unit increase preoperative logmar bcva 009 phacoemulsification performed residents early training log10cde 033 higher ucsf zoc multivariable analysis worse baseline visual acuity age 90 years time surgery decreased odds good bcva 026 per unit increase preoperative logmar bcva 012 age 90 comorbid retinal issues decreased odds good postoperative bcva 013039 greater anterior chamber depth acd shorter axial length al increased odds good postoperative outcome 264 per 1 mm increase acd 084 per 1 mm increase al conclusionscataract grade determined slit lamp exam first time older patient age noted important predictors high cde cde risk factor postoperative bcva measured postoperative 1 month surgery performed trainees supervision lower training level associated higher cde worse postoperative bcva,0.0
sensorytactile functional mapping useassociated structural variation human female genital representation field precise location human female genital representation field primary somatosensory cortex s1 controversial capacity useassociated structural variation function sexual behavior remains unknown used fmricompatible sensorytactile stimulation paradigm functionally map location female genital representation field 20 adult women neural response tactile stimulation clitoral region versus right hand identified individuallydiverse focal bilateral activations dorsolateral areas s1 ba1ba3 alignment anatomical location next used cortical surface analyses assess structural thickness across 10 individually activated vertices per hemisphere woman show frequency sexual intercourse within 12 months correlated structural thickness individuallymapped left genital field results provide precise functional localization female genital field provide support useassociated structural variation human genital cortexsignifcancewe provide precise location human female genital field somatosensory cortex first time provide evidence support structural variation human genital field association frequency genital contact study represents significant methodological advance individually mapping genital fields structural analyses secondary level results suggest study investigating changes human genital field must map field individually achieve sufficient precision results pave way future research plasticity human genital cortex function normal adverse experience well changes pathological conditions ie sexual dysfunction sexual deviation sexual risktaking behavior,0.0
explaining stress coping behaviors patients multiple sclerosis based precede model qualitative directed content analysis background stress can regarded one consequences multiple sclerosis ms factor exacerbating recurring symptoms resulting disease study aimed explain stress coping behaviors patients ms based precede modelmethodsthis study qualitative directed content analysis research based precede model data obtained indepth semistructured interviews 26 patients ms selected using purposive sampling maximum diversity terms gender age education marital status employment data collection continued saturation occurred simultaneously collected data analyzed using qualitative directed content analysis methodresultsdata analysis led identification 11 subcategories 10 subcategories assigned three categories predisposing factors awareness attitude selfefficacy perceived severity enabling factors existence resources access resources skills using resources educational preferences reinforcing factors social support important others behavioral consequences social comparison category new category identified analysis interviewsconclusionsbased results individual environmental social factors play role stress patients designing programs lead empowerment improvements environmental social conditions can effective controlling stress patients based results planners can adopt appropriate strategies change determinants help reduce stress promote psychological standard living patients,0.0
catastrophic seronegative antiphospholipid syndrome case literature review background antiphospholipid syndrome aps multisystemic autoimmune disease characterized arterial venous thrombosis obstetric morbidity presence least one circulating antiphospholipid antibody spectrum vascular events varies deep venous thrombosis catastrophic aps rare form characterized acute multiorgan thrombosis high mortalitycase reportwe present case 32week pregnant woman arriving hospital emergency room bilateral acute lower limb ischemia obstetric evaluation fetal death declared computerized tomography angiography showed pulmonary embolism pulmonary arteries areas splenic right renal infarction multiple arterial venous thrombosis patient underwent urgent caesarean section axillarybifemoral bypass events registered postoperative period intensive care unit treatment rituximab plasmapheresis added anticoagulant therapy laboratorial investigation negative thrombophilia autoimmune diseasesconclusioncatastrophic aps develops quickly multiorgan involvement high mortality rate presented case poses multidisciplinary challenge surgical approach extraanatomical revascularization less invasive guaranteeing immediate perfusion lower limbs although serological tests negative antiphospholipid antibodies case hardly fits another diagnosis therefore treated catastrophic aps shown favorable evolution,0.0
global prevalence myasthenia gravis effectiveness common drugs treatment systematic review metaanalysis background myasthenia gravis neuromuscular autoimmune disorder characterized weakness disability voluntary muscles several preliminary studies epidemiology myasthenia gravis different parts world effectiveness common drugs treatment comprehensive study efficacy common drugs treatment myasthenia gravis therefore study aimed determine epidemiology myasthenia gravis globally effectiveness common drugs treatment using systematic review metaanalysismethodsresearch studies extracted irandoc magiran iranmedex sid sciencedirect web sciences wos proquest medline pubmed scopus google scholar based cochrans sevenstep guidelines using existing keywords extracted mesh browser i2 test used calculate heterogeneity studies begg mazumdar rank correlation tests used assess publication bias data analyzed using comprehensive metaanalysis software version 2 resultsin search descriptive studies based research question 7374 articles found deleting articles unrelated research question finally 63 articles sample size 1 206 961 907 people included metaanalysis prevalence mg worldwide estimated 124 people 95 ci 106145 per 100 000 population analytical studies effectiveness common myasthenia gravis drugs 4672 articles found initially removing articles unrelated research question finally 20 articles sample size 643 people drug group 619 people placebo group included study result combination studies difference mean qmgs score index taking mycophenolate immunoglobulin plasma exchange drugs group patients showed significant decrease 14 077 062 028 respectively p 001 conclusionthe results systematic review drug evaluation patients myasthenia gravis showed mycophenolate immunoglobulin plasma exchange drugs positive effects treatment mg also represents positive effect immunoglobulin plasma exchange reducing sfemg index qmgs index positive effect mycophenolate reducing mgadl index sfemg antiachr antibodies index addition based metaanalysis randomeffect model overall prevalence mg world 124 people per 100 000 population indicates urgent need attention disease prevention treatment,0.0
kallikrein8 blood biomarker detecting amnestic mild cognitive impairment results populationbased heinz nixdorf recall study background kallikrein8 klk8 might early bloodbiomarker alzheimers disease ad examined whether blood klk8 elevated persons amnestic mild cognitive impairment amci precursor ad compared cognitively unimpaired cu controlsmethodsforty cases 80 controls matched sex age 3years participants longitudinal populationbased heinz nixdorf recall study baseline 20002003 standardized cognitive performance assessed 5 t1 10 years baseline t2 cases cu t1 incidental amci t2 controls cu t1 t2 blood klk8 measured t2 using multiple logistic regression association klk8 cases vs controls investigated estimating odds ratios 95 confidence intervals 95ci adjusted interassay variability freezing duration using receiver operating characteristic roc analysis diagnostic accuracy klk8 determined estimating area curve auc 95ci adjusted interassay variability freezing duration age sex resultsthirtyseven participants amci vs 72 cu 367women 71080 meansd years valid klk8 measurements mean klk8 higher cases controls 91166198 pg ml vs78316330 pg ml fully adjusted klk8 increase 500pg ml associated 268 105684 higher chance amci compared cu auc 092 086097 blood klk8 strong discriminator amci cuconclusionthis first populationbased study demonstrate potential clinical utility blood klk8 biomarker incipient ad,0.0
effects socioeconomic factors research systemic sclerosis analysis based long time series bibliometric data background systemic sclerosis ssc rare detrimental disease warranting global research efforts evaluating socioeconomic factors impact country research output ssc help identify solutions advancing researchmethodspublication production ssc 19692018 data structural policy factors member countries collected public sources associations ssc research output countrylevel factors investigated panel regression differenceindifferences analysis assessed causal effects rare disease legislationresultsssc publications demonstrated exponential growth r 09410 r 08845 linear adjustment concentrated highincome countries hics ten countries nine hics published 12 261 775 ssc publications another 87 countries produced none gross domestic products gdp population expenditure research development positively associated ssc publications p 0001 higher health expenditure found associated increased ssc publications hics p 0001 rare disease legislation increased annual publication production 628 95 ci 03900867 p 0001 averagely middleincome countries mics effect especially swift lasting significant impact found gdp per capita female percentage political indicatorsconclusionsssc research output increased time substantial country disparities effective health policies facilitating research expanded especially among mics accelerate research advancement,0.0
bilateral facial colliculus syndrome caused pontine tegmentum infarction case report background bilateral facial colliculus syndrome rare clinical presentation patient pontine infarction herein described case bilateral facial paralysis complete horizontal gaze palsy possibly caused paradoxical embolization patent foramen ovale related strokecase presentationa 55yearold male presented sudden onset complete peripheral facial palsy horizontal gaze palsy valsava maneuver mri revealed symmetric involvement bilateral pontine tegmentum accordance location facial colliculus csf analysis followup mri showed evidence central demyelinating disease subsequent echocardiography revealed patent foramen ovale closure surgery performedconclusionsfacial colliculus syndrome symmetric dorsal pontine tegmentum involvement may rare manifestation posterior circulation stroke,1.0
midterm efficacy sacral nerve stimulation treatment chronic constipation zhonghua wei chang wai ke za zhi 2021 dec 25 24 12 10731078 doi 103760 cmajcn4415302021071900288abstractobjective investigate midterm efficacy sacral nerve stimulation sns chronic constipation methods descriptive case series study conducted patients chronic constipation treated xijing hospital digestive disease february 2013 december 2018 retrospectively enrolled types constipation confirmed based colon slow transit test anorectal manometry defecography xian mayinglong coloproctological hospital study registered china clinical trial registry registration chictrroc16008945 case inclusion criteria 1 constipation diagnosed according rome iii criteria 2 traditional treatment including education diet adjustment laxative biofeedback treatment failed least 1 year 3 constipationrelated organic diseases excluding neurogenic diseases including spinal cord injury multiple sclerosis 21 patients included study 10 males 11 females average age 509 1476 years relevant examination evaluation patients underwent percutaneous nerve evaluation pne patient experienced good response pne 2 3 weeks 50 permanent sns implantation performed improvement clinical symptoms quality life baseline pne latest followup time points compared improvement clinical symptoms including autonomic stool frequency per week autonomic stool days per week defecation time visual analogue scale vas lower score indicates serious symptoms score cleveland clinic constipation score cccs higher score indacates serious symptoms criteria change quality life scored sf36 questionnaires higher score indicates better quality life results 21 patients 18 857 experienced significant improvement symptoms pne 2 patients discontinued treatment due dissatisfaction sixteen patients 762 received permanent sns implantation two underwent bilateral pne implantation patients followedup mean 56 3472 months treatment continuously effective 13 patients 619 including 3 ods 1 stc 9 mixed constipation compared baseline score constipation patients receiving permanent sns implantation latest followup shown median autonomic stool frequency per week increased 10 07 75 010 p0001 median autonomic stool days per week increased 10 07 d 45 07 d p0001 median defecation time decreased 190 840 minutes 40 331 minutes p0001 median cccs decreased 200 1330 90 630 p0001 median vas score increased 90 740 800 1590 p0001 values 8 parts sf36 questionnaire increased p005 conclusion sns implantation safe obvious effects severe constipation stable midterm efficacypmid34923790 doi103760 cmajcn4415302021071900288,0.0
protective role exercise agerelated neurodegeneration ageing res rev 2021 dec 16101543 doi 101016 jarr2021101543 online ahead printabstractendurance exercise widely accessible lowcost intervention variety benefits multiple organ systems exercise improves multiple indices physical performance stimulates pronounced health benefits reducing range pathologies including metabolic cardiovascular neurodegenerative disorders endurance exercise delays brain aging preserves memory cognition improves symptoms neurodegenerative pathologies like amyotrophic lateral sclerosis alzheimers disease parkinsons disease huntingtons disease various ataxias potential mechanisms underlying beneficial effects exercise include neuronal survival plasticity neurogenesis epigenetic modifications angiogenesis autophagy synthesis release neurotrophins cytokines review discuss shared benefits molecular pathways driving protective effects endurance exercise various neurodegenerative diseases animal models humanspmid34923167 doi101016 jarr2021101543,0.0
epilepsy progression associated cumulative dna methylation changes inflammatory genes prog neurobiol 2021 dec 16102207 doi 101016 jpneurobio2021102207 online ahead printabstractmesial temporal lobe epilepsy hippocampal sclerosis mtlehs common focal epilepsy adults characterized alarming rates pharmacoresistance epileptogenesis associated occurrence epigenetic alterations epigenetic studies carried mtlehs mainly focused hippocampus study obtained dna methylation profiles hippocampus anterior temporal neocortex mtlehs patients subjected resective epilepsy surgery autopsied nonepileptic controls assessed progressive nature dna methylation changes relation epilepsy duration identified significantly altered hippocampal dna methylation patterns encompassing multiple pathways known involved epileptogenesis dna methylation changes even striking neocortex wherein pathogenic pathways genes common tissues importantly dna methylation changes many genomic sites varied significantly epilepsy duration progressive changes associated inflammationrelated genes hippocampus results suggest neocortex relatively spared extensive histopathological damage may also involved epilepsy development results also open possibility observed neocortical impairment represent preliminary stage epileptogenesis establishment chronic lesions consequence prolonged seizure exposure twotissue multilevel characterization mtlehs dna methylome suggests occurrence selfpropagating inflammatory wave epigenetic dysregulationpmid34923048 doi101016 jpneurobio2021102207,0.0
influence hladrb115 relationship microglia neurons multiple sclerosis normal appearing cortical grey matter brain pathol 2021 dec 13e13041 doi 101111 bpa13041 online ahead printabstractcortical tissue injury common multiple sclerosis ms associates disability progression previously shown hladrb115 genotype status associates extent cortical inflammatory pathology current study sought examine influence hladrb115 relationships inflammation neurodegeneration ms human postmortem ms cases n 47 controls n 10 used adjacent sections motor cortex stained microglia iba1+ cd68+ tmem119+ lymphocytes cd3+ cd8+ gfap+ astrocytes neurons neun+ subset ms cases n 20 controls n 7 doublelabeled neurofilament glutamic acid decarboxylase 65 67 gad+ assess extent inhibitory synaptic loss ms cases microglial protein expression positively correlated neuron density iba1+ r 0548 p 0001 cd68+ r 0498 p 0001 tmem119+ r 0437 p 0003 finding restricted ms cases carrying hladrb115 evidence 14 reduction inhibitory synapses ms detected ms 0299 0006 synapses m2 neuronal membrane versus control 0348 0009 synapses m2 neuronal membrane p 0005 neurons expressing inhibitory synapses 24 smaller ms cases compared control ms 403 15 m2 versus control 531 29 m2 p 0001 finding driven hladrb115+ cases 15+ 376 21 m2 vs 15 432 22 m2 p 0018 taken together results demonstrate hladrb115 modulates relationship microglial inflammation inhibitory synapses neuronal density ms cortexpmid34904300 doi101111 bpa13041,0.0
inhalation dimethyl fumarateencapsulated solid lipid nanoparticles attenuate clinical signs experimental autoimmune encephalomyelitis pulmonary inflammatory dysfunction mice clin sci lond 2021 dec 14cs20210792 doi 101042 cs20210792 online ahead printabstractrationale fda approved dimethyl fumarate dmf oral drug multiple sclerosis treatment based immunomodulatory activities however also caused severe adverse effects mainly related gastrointestinal systemobjective investigated potential effects solid lipid nanoparticles sln containing dmf administered inhalation clinical signs central nervous system cns inflammatory response lung function changes mice experimental autoimmune encephalomyelitis eae materials methods eae induced using mog3555 peptide female c57bl 6j mice treated via inhalation dmfencapsulated sln ctrl sln dmf eae sln dmf empty sln ctrl sln eae sln saline solution ctrl saline eae saline every 72 hours 21 daysresults 21 days postinduction eae mice treated dmfloaded sln compared eae saline eae sln showed decreased clinical score weight loss reduction brain spinal cord injury inflammation also related increased influx foxp3+ cells spinal cord lung tissues moreover data revealed eae mice showed signs respiratory disease marked increased vascular permeability leukocyte influx production tnf il17 perivascular peribronchial inflammation pulmonary mechanical dysfunction associated loss respiratory volumes elasticity dmfencapsulated reverted sln nebulizationconclusion study suggests inhalation dmfencapsulated sln effective therapeutic protocol reduces cns inflammatory process disability progression characteristic eae disease also protects mice lung inflammation pulmonary dysfunctionpmid34904644 doi101042 cs20210792,0.0
joint mri t1 unenhancing contrastenhancing multiple sclerosis lesion segmentation deep learning opera trials radiology 2021 dec 14211528 doi 101148 radiol211528 online ahead printabstractbackground deep learningbased segmentation facilitate rapid reproducible t1 lesion load assessments crucial disease management multiple sclerosis ms t1 unenhancing contrastenhancing lesions ms enhance enhance administration gadoliniumbased contrast agent t1weighted mri purpose develop deep learning models automated assessment t1 unenhancing contrastenhancing lesions investigate joint training improved performance reproduce known ocrelizumab treatment response evaluate association baseline t1weighted imaging metrics clinical outcomes relapsing ms clinical trials materials methods joint individual deep learning models unets developed retrospectively multimodal mri data sets large multicenter opera trials relapsing ms august 2011 may 2015 joint model included crossnetwork connections combined loss function models trained opera data sets threefold crossvalidation opera ii data sets internal test set dice coefficients lesion truepositive falsepositive rates areas receiver operating characteristic curve aucs used evaluate model performance association baseline imaging metrics clinical outcomes assessed cox proportional hazards models results total 796 patients 3030 visits mean age 37 years 9 521 women opera ii trial evaluated joint model achieved mean dice coefficient 077 074 lesion truepositive rate 088 086 lesion falsepositive rate 004 019 t1 contrastenhancing t1 unenhancing lesion segmentation respectively joint training improved performance smaller t1 contrastenhancing lesions 006 ml individual training auc 075 joint training auc 087 p 001 significant ocrelizumab treatment effect p 001 seen reducing mean number t1 contrastenhancing lesions 24 48 96 weeks manual assessment 24 weeks 10 lesions 366 patients ocrelizumab 141 lesions 355 patients interferon 93 reduction manual assessment 48 weeks six lesions 355 patients ocrelizumab 150 lesions 317 patients interferon 96 reduction manual assessment 96 weeks five lesions 340 patients ocrelizumab 157 lesions 294 patients interferon 97 reduction joint model assessment 24 weeks 19 lesions 365 patients ocrelizumab 128 lesions 354 patients interferon 86 reduction joint model assessment 48 weeks 14 lesions 355 patients ocrelizumab 121 lesions 317 patients interferon 90 reduction joint model assessment 96 weeks 10 lesions 340 patients ocrelizumab 144 lesions 294 patients interferon 94 reduction mean number new t1 unenhancing lesions across followup examinations manual assessment 504 lesions 1060 visits ocrelizumabtreated patients 1438 lesions 965 visits interferontreated patients 68 reduction joint model assessment 205 lesions 1053 visits ocrelizumabtreated patients 661 lesions 957 visits interferontreated patients 78 reduction baseline t1 unenhancing total lesion volume associated clinical outcomes manual hazard ratio hr 112 p 02 joint model hr 111 p 03 conclusion joint architecture training improved segmentation mri t1 contrastenhancing multiple sclerosis lesions deep learning models sufficiently high performance detect ocrelizumab treatment response consistent manual assessments clinicaltrialsgov nct01247324 nct01412333 rsna 2021 online supplemental material available article see also editorial talbott issuepmid34904871 doi101148 radiol211528,0.0
epidemiology acquired demyelinating syndrome children complex opportunity investigate etiopathogenesis multiple sclerosis dev med child neurol 2021 dec 14 doi 101111 dmcn15119 online ahead printno abstractpmid34904715 doi101111 dmcn15119,1.0
immunoadsorption plasma exchangeefficient treatment options neurological autoimmune diseases j clin apher 2021 dec 14 doi 101002 jca21953 online ahead printabstractbackground therapeutic plasma exchange tpe immunoadsorption ia first second line treatment options patients neurological autoimmune diseases including multiple sclerosis neuromyelitis optica spectrum disorders nmsod chronic inflammatory demyelinating polyneuropathy acute inflammatory demyelinating polyradiculoneuropathy guillainbarr syndrome autoimmune encephalitismethods prospective randomized controlled monocentric study assessed safety efficacy therapy ia tpe patients neurological autoimmune diseases treatment response assessed using various neurological scores well measuring immunoglobulin cytokine concentrations clinical outcome evaluated application specific scores underlying diseasesresults total 32 patients analyzed among 19 patients treated tpe 13 patients ia ia tpe therapy showed comparable significant treatment response patients ms nmosd mean edss treatment showed significant reduction treatment ia observed significant reduction proinflammatory cytokines il12 ll17 il6 inf tumor necrosis factor alpha ia treatment whereas reduction seen patients treated tpeconclusions summary ia tpe effective safe procedures treating neurological autoimmune diseases however trend towards longer therapy response patients treated ia compared tpe possibly related reduction plasma levels proinflammatory cytokines seen iatreated grouppmid34904748 doi101002 jca21953,1.0
b cells central nervous system disease diversity locations pathophysiology nat rev immunol 2021 dec 13 doi 101038 s41577021006526 online ahead printabstractb cells represent relatively minor cell population within healthy diseased central nervous system cns yet can profound effects emphasized multiple sclerosis b celldepleting therapies arguably efficacious treatment condition review discuss b cells enter persist cns many neurological conditions b cells concentrate within cns barriers rarely found parenchyma highlight b cells can contribute cns pathology antibody secretion antigen presentation secretion neurotoxic molecules using examples cns tumours cns infections autoimmune conditions neuromyelitis optica particular multiple sclerosis overall understanding common divergent principles b cell accumulation effects within cns offer new insights treating devastating neurological conditionspmid34903877 doi101038 s41577021006526,0.0
astrocyte control entorhinal cortexdentate gyrus circuit relevance cognitive processing impairment pathology glia 2021 dec 14 doi 101002 glia24128 online ahead printabstractthe entorhinal cortexdentate gyrus circuit centrally involved memory processing conveying hippocampus spatial nonspatial context information via respectively medial lateral perforant path mpp lpp excitatory projections onto dentate granule cells gcs review work several years group showing astrocytes sense local synaptic transmission exert turn presynaptic control ppgc synapses modulation neurotransmitter release probability astrocytes sets basal synaptic strength dynamic range longterm potentiation ppgc synapses intriguingly astrocyte control circuitspecific present mppgc lppgc synapses selectively express atypical presynaptic nmethyldaspartate receptors nmdar suitable activation astrocytereleased glutamate moreover astrocytic control peculiarly dependent cytokine tnf constitutive levels acts gating factor astrocyte signaling inflammation infection processes increased levels tnf lead uncontrolled astrocyte glutamate release altered ppgc circuit processing ultimately impaired contextual memory performance tnfdependent pathological switch synaptic control astrocytes deleterious consequences observed animal models hiv brain infection multiple sclerosis conditions known cause cognitive disturbances 50 patients review also discusses open issues related identified astrocytic pathway role contextual memory processing potential damaging role alzheimers disease existence vesicular glutamate release dg astrocytes possible synapticlike connectivity astrocytic output sites pp receptive sitespmid34904753 doi101002 glia24128,0.0
deep learning opera trials multiple sclerosis radiology 2021 dec 14212733 doi 101148 radiol212733 online ahead printno abstractpmid34904878 doi101148 radiol212733,0.0
mitigating site effects covariance machine learning neuroimaging data hum brain mapp 2021 dec 14 doi 101002 hbm25688 online ahead printabstractto acquire larger samples answering complex questions neuroscience researchers increasingly turned multisite neuroimaging studies however studies hindered differences images acquired across multiple sites effects shown bias comparison sites mask biologically meaningful associations even introduce spurious associations address field focused harmonizing data removing siterelated effects mean variance measurements contemporaneously increase popularity multicenter imaging use machine learning ml neuroimaging also become commonplace approaches shown provide improved sensitivity specificity power due modeling joint relationship across measurements brain work demonstrate methods removing site effects mean variance may sufficient ml stems fact methods fail address correlations measurements can vary across sites data alzheimers disease neuroimaging initiative used show considerable differences covariance exist across sites popular harmonization techniques address issue propose novel harmonization method called correcting covariance batch effects covbat removes site effects mean variance covariance apply covbat show withinsite correlation matrices successfully harmonized furthermore find ml methods unable distinguish scanner manufacturer proposed harmonization applied covbatharmonized data retain accurate prediction disease grouppmid34904312 doi101002 hbm25688,0.0
validity chronic disease diagnoses icelandic healthcare registries scand j public health 2021 dec 1314034948211059974 doi 101177 14034948211059974 online ahead printabstractaims evaluate validity recorded chronic disease diagnoses icelandic healthcare registriesmethods eight different chronic diseases multiple subspecialties medicine validated respect accuracy timeliness disease 30 patients recorded diagnosis 30 patients without diagnosis randomly selected 80 000 participants istopmm trial includes 54 icelandic population born 1976 case validated chart review physicians using predefined criteriaresults overall accuracy chronic disease diagnoses 96 95 ci 9497 ranging 92 98 individual diseases weighting disease prevalence accuracy estimated 985 overall positive predictive value ppv chronic disease diagnosis 93 95 ci 8996 overall negative predictive value npv 99 95 ci 96100 diseasespecific differences validity notably multiple sclerosis ppv 83 disorders ppvs 93 97 npv disorders 100 except hypertension heart failure 97 93 respectively registered chronic disease objective findings disease 96 casesconclusions determining presence chronic disease diagnosis data icelandic healthcare registries high ppv npv accuracy furthermore diagnoses can confirmed objective findings imaging blood testing findings can inform interpretation studies using diagnostic data icelandic healthcare registriespmid34903105 doi101177 14034948211059974,0.0
c1q inhibits differentiation oligodendrocyte progenitor cells via wnt#x2f betacatenin signaling activation cuprizoneinduced mouse model multiple sclerosis exp neurol 2021 dec 10113947 doi 101016 jexpneurol2021113947 online ahead printabstractmultiple sclerosis ms chronic central nervous system demyelinating disease autoimmune originate complement c1q complex glycoprotein mediates variety immunoregulatory functions considered important prevention autoimmunity although found increased serum c1q level highly associated fazekas scores t2 lesion volume ms patients effect mechanism c1q demyelination remains unclear cluster analysis protein array results showed serum wnt receptors frizzled6 lrp6 levels ms patients increased proposed c1q may involved demyelination via wnt signaling increased c1q protein levels serum brain tissue confirmed cuprizone cpz induced demyelination mice model moreover cpz treatment induced significant increase lrp6 frizzled6 protein mice corpus callosum lrp6 extracellular domain lrp6ecd level serum cerebrospinal fluid csf cpz mice also significantly increased knockdown subunit c1s c1 substantially attenuated demyelination promoted m2 microglia polarization improved neurological function inhibited catenin expression nuclear translocation oligodendrocyte progenitor cells opcs vitro c1s silence reversed increased level lrp6ecd medium catenin expression opcs induced c1q treatment meanwhile inhibition c1s also markedly lowered number edu positive opcs enhanced number cnpase positive oligodendrocyte protein mbp present study indicated c1q involved demyelination response cpz mice preventing opc differentiating mature oligodendrocyte via wnt catenin signaling activationpmid34902359 doi101016 jexpneurol2021113947,1.0
characterization clinical evidence supporting repository corticotropin injection fdaapproved indications scoping review jama intern med 2021 dec 13 doi 101001 jamainternmed20217171 online ahead printabstractimportance repository corticotropin injection expensive medication approved 1952 treatment many inflammatory conditions clinical evidence supporting use repository corticotropin hereinafter referred corticotropin weak perhaps approval predated modern review standards us food drug administration fda objective characterize clinical evidence supporting use corticotropin fdaapproved indicationsevidence review studies identified via electronic searches ovid medline cumulative index nursing allied health literature cinahl cochrane central register controlled trials central database inception may 12 2021 medline search updated june 8 2021 bibliographies retrieved articles also reviewed clinicaltrialsgov fda documents manufacturers website search terms included hp acthar acth gel repository corticotropin terms specific diseases multiple sclerosis nephrotic syndrome rheumatoid arthritis west syndrome spasms infantile review included randomized clinical trials rcts nonrandomized singlearm clinical trials prospective cohort studies compared corticotropin active comparator placebo treatment data extracted 1 reviewer verified second disagreements resolved discussion studies qualitatively synthesized indication summarize important design features resultsfindings 1059 records screened 203 fulltext articles assessed eligibility total 41 studies involving 2235 participants met inclusion criteria 11 involved infantile spasms 10 involved multiple sclerosis ms 11 involved rheumatological conditions 7 involved nephrotic syndrome 1 involved ocular conditions 1 involved sarcoidosis overall 19 studies either included single arm exclusively compared different corticotropin dosing strategies evidence robust treatment infantile spasms ms largest number studies comparing corticotropin active agent n 4 placebo n 5 pertained ms almost studies finding corticotropin performed better placebo different corticosteroids treatment infantile spasms 8 controlled studies identified 6 randomized 1 small rct found corticotropin significantly superior corticosteroids studies patients conditions n 20 frequently lacked control group n 12 placebocontrolled n 5 exclusively examined different corticotropin dosing strategies n 2 placebocontrolled rcts rheumatoid arthritis ankylosing spondylitis optic neuritis systemic lupus erythematosus nephrotic syndrome generally small consistently demonstrate corticotropin superior placebo blinded rcts showed similar greater number adverse effects corticotropin relative corticosteroidsconclusions relevance scoping review rcts supported clinical benefit corticotropin fdaapproved indications rcts found corticotropin superior corticosteroids treating relapses ms infantile spasmspmid34902005 doi101001 jamainternmed20217171,0.0
cd40l protects mouse hepatitis virusinduced neuroinflammatory demyelination plos pathog 2021 dec 13 17 12 e1010059 doi 101371 journalppat1010059 online ahead printabstractneurotropic mouse hepatitis virus mhva59 rsa59 infection mice induces acute neuroinflammation due direct neural cell dystrophy proceeds demyelination without axonal loss pathological hallmarks human neurological disease multiple sclerosis ms recent studies rsa59induced neuroinflammation model ms showed protective role cnsinfiltrating cd4+ t cells compared pathogenic role autoimmune model current study investigated molecular nexus cd4+t cellexpressed cd40ligand microglia macrophageexpressed cd40 using cd40l mice results demonstrate cd40l expression cns modulated upon rsa59 infection show evidence cd40l mice susceptible rsa59 induced disease due reduced microglia macrophage activation significantly dampened effector cd4+ t recruitment cns day 10 pi additionally cd40l mice exhibited severe demyelination mediated phagocytic microglia macrophages axonal loss persistent poliomyelitis chronic infection indicating cd40cd40l hostprotective rsa59induced demyelination suggests novel target designing prophylaxis virusinduced demyelination axonal degeneration contrast immunosuppression holds autoimmune mechanisms inflammatory demyelinationpmid34898656 doi101371 journalppat1010059,1.0
bibliometric analysis carbon exchange global drylands j arid land 2021 dec 4114 doi 101007 s4033302101123 online ahead printabstractdrylands refer regions aridity index lower 065 billions people depend services provided critically important ecosystems areas ecosystem carbon exchange global drylands ced occurs climate change affects ced critical global carbon cycle performed comprehensive bibliometric study fields annual publications marked journals marked institutions marked countries popular keywords temporal evolution understand temporal trends ced research past 30 19912020 found annual scientific publications ced research increased significantly average growth rate 793 agricultural water management ranked first among journals citations ten productive institutions centered drylands america china australia largest number citations publications ced research climate change climaterelated drought precipitation temperature rainfall research found popular study areas keywords classified five clusters indicating five main research focuses ced studies hydrological cycle effects climate change carbon water balance productivity carbonnitrogenphosphorous coupling cycles temporal evolution keywords showed areas focus ced studies transformed classical pedology agricultural research applied ecology global change ecological research past 30 future ced studies basic themes water yield salinity motor themes climate change sustainability remote sensing will focus research ced particular multiple integrated methods understand climate change ecosystem sustainability potential new research trends hotspotspmid34899874 pmcpmc8643123 doi101007 s4033302101123,0.0
sarscov2 memory b t cells profile mild covid19 convalescents subjects int j infect dis 2021 dec 8s12019712 21 012030 doi 101016 jijid202112309 online ahead printabstractobjectives antiviral adaptive immunity involves memory b mbc tcells mtc however dynamics sarscov2 convalescents warrant investigationmethods crosssectional longitudinal study evaluated bloodderived mbc mtcresponses 68 antispike iggpositive mildcovid19 convalescents visit 1 17 months median 41 months disease onset sarscov2 antispike igg performed elisa mbc sarscov2 specific receptor binding domain rbd elispot interferon gamma ifng interleukin 2 il2 ifng+il2 secreting mtc ifng il2 sarscov2 fluorospot 24 patients sampled first visit igg mbc mtc analysis also performed 3 months later second visitresults seventy two percent mbc mtcpositive 18 mbcpositive mtcnegative 10 mtcpositive mbcnegative peak mbcresponse level detected 3 months covid19 onset persisted 7 months post infection significant mtclevels detected one month onset response s1 s2_n snmo peptide pools frequency magnitude mtc response snmo higher s1 s2_n longitudinal analysis demonstrated even specific humoral immunity declined cellular immunity persistedconclusion findings demonstrate durability adaptive cellular immunity least 7months sarscov2 infection suggest longlasting protectionpmid34896265 doi101016 jijid202112309,0.0
interferonbeta fingolimod control microglial inflammatory cell polarization response multiple sclerosisassociated bacterial ligand 654 arch med res 2021 dec 8s01884409 21 002228 doi 101016 jarcmed202111002 online ahead printabstractbackground aims many endogenous exogenous risk factors associated multiple sclerosis ms recent studies suggest microbiomederived ligands play role disease process goal study characterize cellular response elicited human microglia upon treatment ifn fingolimod two first line medications management ms determine whether treatments affect response microglial cells msassociated bacterial ligand lipid 654materials methods hmc3 human microglial cells treated ifn fingolimod cytokine secretion evaluated using multiplex system microglia polarization assessed flow cytometryresults observed treatment ifn fingolimod induced differential secretion various proinflammatory cytokines upon cell stimulation lipid 654 observed ifn fingolimod decreased secretion m1associated cytokines using flow cytometry observed decrease inflammatory cytokine secretion likely due containment m1 phenotype microglia stimulation lipid 654conclusions findings provide new clues still unknown mechanisms action ifn fingolimod human microglia will prompt new avenues research use therapies regulation inflammatory response mspmid34895764 doi101016 jarcmed202111002,0.0
therapeutic effect novel curcumin derivative gt863 mouse model amyotrophic lateral sclerosis amyotroph lateral scler frontotemporal degener 2021 dec 1117 doi 101080 2167842120212012699 online ahead printabstractthe present study investigated therapeutic effects curcumin derivative 3 1e 2 1hindol6yl ethenyl 5 1e 2 2methoxy4 2pyridylmethoxy phenyl ethenyl 1hpyrazole gt863 amyotrophic lateral sclerosis als inhibitory effect gt863 superoxide dismutase 1 sod1 aggregation evaluated cellfree assays gt863 interfered conformational changes sod1 protein later oligomeric aggregation furthermore antioxidant antiinflammatory neuroprotective effects evaluated cellfree cultured cell assays gt863 inhibited h2o2 glutamateinduced cytotoxicity activated antioxidant responsive element pathway additionally vivo effects gt863 als mice model evaluated oral administration h46r mutant sod1 transgenic mice rotarod test showed gt863 administration significantly slowed progression motor dysfunction mice addition gt863 substantially reduced highlyaggregated sod1 preserving large neurons spinal cord gt863treated mice collectively results indicated gt863 viable therapeutic agent multiple vital actions treatment alspmid34894926 doi101080 2167842120212012699,1.0
deeplesionbrain towards broader deeplearning generalization multiple sclerosis lesion segmentation med image anal 2021 nov 27 76102312 doi 101016 jmedia2021102312 online ahead printabstractrecently segmentation methods based convolutional neural networks cnns showed promising performance automatic multiple sclerosis ms lesions segmentation techniques even outperformed human experts controlled evaluation conditions longitudinal ms lesion segmentation challenge isbi challenge however stateoftheart approaches trained perform well highlycontrolled datasets fail generalize clinical data unseen datasets instead proposing another improvement segmentation accuracy propose novel method robust domain shift performing well unseen datasets called deeplesionbrain dlb generalization property results three main contributions first dlb based large group compact 3d cnns spatially distributed strategy aims produce robust prediction despite risk generalization failure individual networks second propose hierarchical specialization learning hsl pretraining generic network whole brain using weights initialization locally specialized networks end dlb learns generic features extracted global image level specific features extracted local image level finally dlb includes new image quality data augmentation reduce dependency training data specificity eg acquisition protocol dlb generalization validated crossdataset experiments msseg16 isbi challenge inhouse datasets experiments dlb showed higher segmentation accuracy better segmentation consistency greater generalization performance compared stateoftheart methods therefore dlb offers robust framework wellsuited clinical practicepmid34894571 doi101016 jmedia2021102312,0.0
bacterial neurotoxic metabolites multiple sclerosis cerebrospinal fluid plasma brain 2021 dec 11awab320 doi 101093 brain awab320 online ahead printabstractthe identification intestinal dysbiosis patients neurological psychiatric disorders highlighted importance gutbrain communication yet question regarding identity components responsible cross talk remains open previously reported relapsing remitting multiple sclerosis patients rrms treated dimethyl fumarate prominent depletion gut microbiota thereby suggesting studying composition plasma cerebrospinal fluid csf samples patients may help identify microbially derived metabolites used functional xenogeneic assay consisting cultured rat neurons exposed csf samples collected multiple sclerosis patients dimethyl fumarate treatment assess neurotoxicity conducted metabolomic analysis plasma csf samples identify metabolites differential abundance weighted correlation network analysis allowed us identify groups metabolites present plasma csf samples whose abundance correlated neurotoxic potential csf analysis identified presence phenol indole group metabolites bacterial origin eg pcresolsulfate indoxylsulfate nphenylacetylglutamine potentially neurotoxic decreased treatment chronic exposure cultured neurons metabolites impaired firing rate induced axonal damage independent mitochondrial dysfunction oxidative stress thereby identifying novel pathway neurotoxicity clinical radiological cognitive test metrics also collected treated patients followup visits improved mri metrics disability cognition detected dimethyl fumarate treated rrms patients levels identified metabolites bacterial origin pcresolsulfate indoxylsulfate nphenylacetylglutamine inversely correlated mri measurements cortical volume directly correlated levels neurofilament light chain established biomarker neurodegeneration data suggest phenol indole derivatives catabolism tryptophan phenylalanine microbially derived metabolites may mediate gutbrain communication induce neurotoxicity multiple sclerosispmid34894211 doi101093 brain awab320,0.0
sarscov2 vaccine patients systemic sclerosis impact disease subtype therapy rheumatology oxford 2021 dec 11keab886 doi 101093 rheumatology keab886 online ahead printabstractobjective analyse safety immunogenicity factors affecting antibody response severe acute respiratory syndromecoronavirus2 sarscov2 vaccination patients systemic sclerosis ssc methods phase 4 prospective study within larger trial two doses inactivated sarscov2 vaccine coronavac 51 ssc patients compared 153 controls antisarscov2igg neutralizing antibodies nab assessed vaccine shot d0 d28 6 weeks 2nd dose d69 individuals negative baseline igg nab coronavirus19 covid19 followup vaccine safety also assessed participantsresults patients controls comparable median ages 48 38557 vs 48 3857 years p 0945 patients mostly diffuse ssc 686 majority 745 interstitial lung disease patients immunosuppressive therapy 725 mainly mycophenolate mofetil mmf 529 full vaccination d69 antisarscov2igg frequency 641 vs 942 p 0001 nab positivity 538 vs 769 p 0006 moderate although lower controls first dose response d28 low comparable sc p 0958 nab positivity p 0537 ssc patients mmf monotherapy vs therapy dmards lower immunogenicity sc 313 vs 90 p 0001 nab 188 vs 85 p 0001 multiple regression analysis confirmed mmf use disease subtype associated insufficient seroconversion odds ratio 0056 95ci 00090034 p 0002 nab positivity 0047 95ci 00070036 p 0002 moderate severe sideeffects observedconclusion coronavac excellent safety profile moderate response antisarscov2 vaccine ssc vaccine antibody response influenced disease subtype greatly affected mmf reinforcing need additional strategies upmodulate vaccine response subgroup patientstrial registration clinicaltrialsgov https clinicaltrialsgov nct04754698pmid34894235 doi101093 rheumatology keab886,0.0
impact natural killer nk cells immune reconstitution potential biomarker disease activity alemtuzumabtreated patients relapsing remitting multiple sclerosis observational study cns drugs 2021 dec 11 doi 101007 s40263021008750 online ahead printabstractbackground defining immune mechanisms leading multiple sclerosis ms difficult due great interindividual difference immune system responses anticd52 antibody alemtuzumab transiently abolishes differences immune parameters among individuals allowing analysis subsequent immune cell repopulation patterns possible role msobjective evaluate correlation innate adaptive immune cell subsets disease activity ms context treatment alemtuzumabmethods twocenter observational cohort patients treated alemtuzumab underwent immune profiling t b natural killer nk cells biomarker clinical radiological followupresults treatment percentage nk b cells increased nk t bcell populations underwent profound rearrangement within effector tcell compartment treatment led transient decrease followed increase thelper 1 cells transient decrease thelper 17 cells within tregulatory compartment nave tregulatory cells increased within bcell compartment memory b cells mature b cells decreased whereas transitional b cells increased within nk cell compartment cd56bright nk cells increased subjects without disease activity greater decrease serum nfl greater nk cell cd3+ t cell ratio nk cell numbers baseline treatment influenced reconstitution t b cells inversely correlated reconstitution proinflammatory cd3+ t cells mature b cells directly correlated increase transitional b cellsconclusions results study provide novel evidence nk cells influence reconstitution adaptive immune cells upon alemtuzumab patients successful response alemtuzumab early immune reconstitution dominated nk cellspmid34894339 doi101007 s40263021008750,0.0
cladribine potential object nucleoside transporterbased drug interactions clin pharmacokinet 2021 dec 11 doi 101007 s40262021010899 online ahead printabstractcladribine nucleoside analog phosphorylated target cells b tlymphocytes active triphosphate form 2chlorodeoxyadenosine triphosphate cladribine tablets 10 mg mavenclad administered 10 days per year 2 consecutive years 35mg kg cumulative dose 2 years used treat patients relapsing multiple sclerosis cladribine shown substrate various nucleoside transporters nts intestinal absorption distribution cladribine throughout body appear essentially mediated equilibrative nts ents concentrative nts cnts specifically ent1 ent2 ent4 cnt2 low affinity cnt3 efficient transporters cladribine abc efflux transporters specifically breast cancer resistance protein likely modulates oral absorption renal excretion cladribine key transporter intracellular uptake cladribine b tlymphocytes ent1 ancillary contributions ent2 cnt2 transporterbased drug interactions affecting absorption target cellular uptake prodrug cladribine likely reduce systemic bioavailability target cell exposure thereby possibly hampering clinical efficacy order manage optimized therapy ie ensure uncompromised target cell uptake preserve full therapeutic potential cladribine important clinicians aware existence ntinhibiting medicinal products various lifestyle drugs food components article reviews existing knowledge inhibitors nt may alter cladribine absorption distribution uptake target cells thereby summarizing existing knowledge optimized methods administration concomitant drugs avoided cladribine treatmentpmid34894346 doi101007 s40262021010899,0.0
investigation serum levels orexina transforming growth factor beta leptin patients multiple sclerosis j clin lab anal 2021 dec 11e24170 doi 101002 jcla24170 online ahead printabstractbackground multiple sclerosis ms chronic inflammatory autoimmune disease affecting various inflammatory nutritional parameters therefore study aimed investigate relationship body mass index bmi ms patients serum levels leptin orexina transforming growth factor tgf methods crosssectional study included 25 patients suffering ms 40 healthy individuals case control groups respectively serum levels leptin orexina tgf assessed participants using enzymelinked immunosorbent assay methods moreover data analyzed using descriptive statistical indices ttest chisquare test linear regression testresults according results participants mean age 3804 753 4023 588 case control groups respectively also groups significantly different gender age alcohol consumption smoking p 005 found mean serum levels orexina tgf significantly lower ms patients compared control group mean serum leptin levels significantly higher 428 vs 189 ng ml p 0001 moreover significant relationship bmi ms patients serum levels orexina tgf leptin p 005 conclusions conclusion found significantly lower levels orexina tgf significantly higher level leptin ms patients compared control group addition significant relationship bmi serum levels orexina tgf leptin ms patientspmid34894407 doi101002 jcla24170,0.0
epigenetic control epsteinbarr lifecycle curr opin virol 2021 dec 7 527888 doi 101016 jcoviro202111013 online ahead printabstractepsteinbarr virus ebv infects 95 adults worldwide causes infectious mononucleosis etiologically linked multiple sclerosis associated 200 000 cases cancer year ebv manipulates host epigenetic pathways switch series latency programs reactivate latency order colonize memory bcell compartment lifelong infection ultimately spread new hosts review recent advances understanding epigenetic mechanisms control ebv latency lytic gene expression ebvtransformed b epithelial cells highlight newly appreciated roles dna methylation epigenetic machinery host histone chaperones hippo pathway m6a rna modification nonsense mediated decay control ebv lifecyclepmid34891084 doi101016 jcoviro202111013,0.0
evaluation quality care pathway patients multiple sclerosis france results original study cohort 700 patients rev neurol paris 2021 dec 7s00353787 21 007669 doi 101016 jneurol202109008 online ahead printabstractintroduction evaluating quality care pathway patients chronic diseases multiple sclerosis ms important issue process indicators recognized method evaluating professional practices however tools little developed field ms data available aim study describe retrospectively validated indicators quality care pathway populationbased cohort 700 patients first manifestations disease occurring january 1 2000 december 31 2001 first 10 years diseasemethod assessment based 48 indicators specific ms information required calculation indicator collected source files 700 patients cohortresults data 10 years followup collected 80 patients total 36 indicators calculated results reveal room improvement particularly terms initial assessment access ophthalmological evaluation employment obtaining evaluation need rehabilitation access careconclusion results survey provide access unprecedented new data france professionals patients can appropriate improve targeting actions improve quality care patients ms france propose continue process submitting discussion targeted list updated indicators relating changes guidelines issues concerning quality patient managementpmid34893353 doi101016 jneurol202109008,0.0
developing communityengaged wheelchair exercise program persons ms community advisory board formation feedback disabil rehabil assist technol 2021 dec 1018 doi 101080 1748310720212010819 online ahead printabstractpurpose exercise safe evidencebased approach improving symptoms mobility impairment cognitive dysfunction fatigue however persons multiple sclerosis ms use wheelchairs mobility excluded research paper describes approach recruiting ten community advisor board cab members partnering developing novel homebased exercise training program wheelchair users msmaterials methods exercise training program developed based initial qualitative research includes progressive exercise prescription equipment oneonone behavioural coaching based social cognitive theory cab members convened groups five people five meetings online using virtual conference software cab meetings lasted approximately 1hour notes transcribed digital format data analysesresults content analysis identified elements aligned meeting foci ie prescription equipment coaching outcomes feedback divided categories refine program specifically modifying adding retaining content activities cab member feedback positive emphasised potential additions materials presented research team proposed implementing modifications based cab member feedback adding wrist weights equipment options completing resistance training exercisesconclusions overall cab feedback invaluable assessing appropriateness proposed exercise training program initiating feasibility testing report provides model guidance researchers seek communityengaged research approaches creating products interventionsimplication rehabilitationcommunity advisory board participation invaluable creating modifying novel exercise training programmes wheelchair users multiple sclerosis ms current study provides framework creation exercise interventions subpopulations persons ms may provide substantial rehabilitation benefits improved symptoms quality lifehealth behaviour interventists targeting individuals disabilities may consider benefits recruiting stakeholders community creation novel programmespmid34892990 doi101080 1748310720212010819,0.0
csf kappa free light chains cutoff validation diagnosing multiple sclerosis mayo clin proc 2021 dec 7s00256196 21 007102 doi 101016 jmayocp202109014 online ahead printabstractobjective determine validate cerebrospinal fluid csf kcsf value statistically comparable detection csfspecific oligoclonal bands ocb support diagnosis multiple sclerosis ms patients methods total 702 retrospective 657 prospective paired csf serum samples residual waste samples physicianordered ocb tests obtained tested kcsf mayo clinic charts reviewed neurologist blinded kcsf results specificity sensitivity ms diagnosis evaluated establish diagnostic cutoff value kcsf retrospective cohort validated prospective cohortresults retrospective prospective subgroups respectively included ms n85 70 nonms n615 585 undetermined diagnosis excluded n2 2 retrospective data established kcsf cutoff value 01 mg dl comparable ocb testing retrospective subgroup kcsf vs ocb sensitivities diagnosis ms 682 vs 750 p08 specificities 861 vs 876 p27 kcsf area receiver operating characteristic curve 0772 95 ci 0720 0824 ocb 0813 95 ci 0764 0861 prospective cohort used validate diagnostic kcsf value 01 mg dl kcsf vs ocb sensitivities 786 p99 specificities 871 vs 894 p09 conclusion kcsf value 01 mg dl valid alternative ocb testing offering standardized quantitative measure eliminating human error reducing cost turnaround time significant difference sensitivity specificity study provides class evidence kcsf value 01 mg dl can used place ocb testing support diagnosis mspmid34893322 doi101016 jmayocp202109014,0.0
tumefactive multiple sclerosis inflammatory demyelinating disease large lesions eur j neurol 2021 dec 10 doi 101111 ene15210 online ahead printno abstractpmid34890080 doi101111 ene15210,1.0
randomized placebocontrolled phase 3 study mesenchymal stem cells induced secrete high levels neurotrophic factors amyotrophic lateral sclerosis muscle nerve 2021 dec 10 doi 101002 mus27472 online ahead printabstractintroduction aims amyotrophic lateral sclerosis als fatal neurodegenerative illness great unmet patient need aimed evaluate whether mesenchymal stem cells induced secrete high levels neurotrophic factors mscntf novel autologous celltherapy capable targeting multiple pathways safely slow als disease progressionmethods randomized doubleblind placebocontrolled study enrolled als participants meeting revised el escorial criteria revised als functional rating scale alsfrsr 25 screening 3 alsfrsr points decline prior randomization participants received three treatments mscntf placebo intrathecally primary endpoint evaluated efficacy mscntf responder analysis safety change disease progression posttreatment 125 points month defines clinical response prespecified analysis leveraged baseline alsfrsr 35 subgroup thresholdresults overall mscntf treatment well tolerated safety concerns thirtythree percent mscntf 28 placebo participants met clinical response criteria 28 weeks or133 p045 thus primary endpoint met prespecified analysis participants baseline alsfrsr35 n58 showed clinical response rate 28 weeks 35 mscntf 16 placebo or26 p029 significant improvements csf biomarkers neuroinflammation neurodegeneration neurotrophic factor support observed mscntf placebo unchangeddiscussion study reach statistical significance primary endpoint however prespecified subgroup suggests mscntf participants less severe disease may retained function compared placebo given unmet patient need results trial warrant investigation article protected copyright rights reservedpmid34890069 doi101002 mus27472,0.0
correction pain quality life religiosity people multiple sclerosis neurol sci 2021 dec 10 doi 101007 s1007202105814x online ahead printno abstractpmid34890003 doi101007 s1007202105814x,0.0
multiple sclerosis myelin basic protein insights protein disorder disease amino acids 2021 dec 10 doi 101007 s00726021031117 online ahead printabstractmyelin basic protein mbp abundant protein central nervous system cns myelin mbp long studied factor pathogenesis autoimmune neurodegenerative disease multiple sclerosis ms ms characterized cns inflammation demyelination axonal loss one main theories pathogenesis ms suggests exposure foreign antigens causes activation crossreactive t cells genetically susceptible individuals mbp possible autoantigen direct role mbp primary antigen human ms unclear clear mbp functions myelin formation longterm maintenance linked ms review looks key molecular characteristics mbp relevance ms well mechanisms possible molecular mimicry mbp viral antigens also discuss use serum antimyelin antibodies biomarkers disease mbp prime example apparently simple fact biochemically structurally complex molecule closely linked normal nervous system development neurodegenerative diseasepmid34889995 doi101007 s00726021031117,1.0
therapeutic effects physical exercise mesenchymal stem cell secretome modulating neuroinflammatory response multiple sclerosis curr stem cell res ther 2021 dec 9 doi 102174 1574888x16666211209155333 online ahead printabstractmultiple sclerosis ms neurodegenerative demyelinating chronic inflammatory disease characterized central nervous system cns lesions lead high levels disability severe physical cognitive disturbances conventional therapies enough control neuroinflammatory process ms able inhibit ongoing damage cns thus secretome mesenchymal stem cells mscs postulated potential therapy mitigate symptoms disease progression considered combination physical exercise ex induce superior effects increase mscs effectiveness condition recent studies revealed ex mscs share similar mechanisms action mitigate autoreactive t cell infiltration regulate local inflammatory response modulate proinflammatory profile glial cells reduce neuronal damage clinical experimental studies reported treatments isolated way also improve myelination regeneration promote release neurotrophic factors increase recruitment endogenous stem cells together effects reduce disease progression improve patient functionality despite results combination methods yet studied ms review focus molecular elements cellular responses induced treatments separate way showing beneficial effects control symptoms disease progression ms well indicating contribution clinical fields addition propose combined use ex mscs strategy boost reparative immunomodulatory effects condition combining benefits synaptogenesis neurogenesis remyelination neuroinflammatory response findings reported based scientific evidence professional experience will bring significant progress regenerative medicine deal conditionpmid34886779 doi102174 1574888x16666211209155333,1.0
maximising abilities negotiating generating exercise options manage people multiple sclerosis feasibility randomised controlled trial clin rehabil 2021 dec 92692155211064949 doi 101177 02692155211064949 online ahead printabstractobjective investigate feasibility preliminary efficacy group selfmanagement exercise education program people multiple sclerosisdesign feasibility randomised controlled trialsetting outpatient rehabilitation facilitysubjects twentythree adults age 486 117 years recruited multiple sclerosis clinic registerinterventions intervention group undertook 12week group program incorporating behaviour change education exercise community integration compared waitlist control groupmain measures feasibility measured recruitment adherence safety efficacy outcomes included measures physical function 6metre 6min walk functional reach selfreport questionnaires fatigue quality life exercise benefits barriers baseline 6 12 24 weeksresults 74 individuals identified register 48 65 contacted deemed eligible 23 48 agreed participate high adherence attendance education 57 72 79 exercise 135 174 78 sessions adverse safety events occurred within intervention sessions missed attendances assessment sessions high 5 8 participants missed time point predominately due health issues intervention group demonstrated positive changes walking endurance functional reach fatigue whereas control reductions walking speed perceived exercise barriersconclusions manage program appears feasible safe people mildtomoderate multiple sclerosis high adherence exercise education sessions future trials consider strategies flexible scheduling alternative methods data collection improve followup assessment attendancepmid34881669 doi101177 02692155211064949,0.0
noddi reveals brain microstructural changes multiple sclerosis nat rev neurol 2021 dec 8 doi 101038 s4158202100600x online ahead printno abstractpmid34880470 doi101038 s4158202100600x,0.0
structure pathological tdp43 filaments als ftld nature 2021 dec 8 doi 101038 s41586021041993 online ahead printabstractthe abnormal aggregation tar dnabinding protein 43 kda tdp43 neurons glia defining pathological hallmark neurodegenerative disease amyotrophic lateral sclerosis als multiple forms frontotemporal lobar degeneration ftld 1 2 also common diseases including alzheimers parkinsons diseasemodifying therapies exist conditions early diagnosis possible structures pathological tdp43 aggregates unknown used cryoelectron microscopy determine structures aggregated tdp43 frontal motor cortices individual als ftld frontal cortex second individual diagnosis identical amyloidlike filament structure comprising single protofilament found brain regions individuals ordered filament core spans residues 282360 tdp43 lowcomplexity domain adopts previously undescribed doublespiralshaped fold shows similarity tdp43 filaments formed vitro3 4 abundance glycine neutral polar residues facilitates numerous turns restricts strand length results absence sheet stacking associated cross amyloid structure uneven distribution residues gives rise structurally chemically distinct surfaces face external densities suggest possible ligandbinding sites work enhances understanding molecular pathogenesis als ftld informs development diagnostic therapeutic agents target aggregated tdp43pmid34880495 doi101038 s41586021041993,0.0
cannabinoid interventions improving cachexia outcomes cancer systematic review metaanalysis j cachexia sarcopenia muscle 2021 dec 8 doi 101002 jcsm12861 online ahead printabstractcancerassociated cachexia cac wasting syndrome characterized involuntary weight loss anorexia clear definition diagnostic criteria cac lacking makes difficult estimate prevalence interpret research compare studies standard treatment manage cac previous studies support use cannabinoids cachexia chronic diseases including hiv multiple sclerosis however randomized controlled trials rcts one metaanalysis intervention cancer populations available nonrandomized studies interventions nrsis often excluded reviews due variable methodology potential biases review aimed consider nrsis alongside rcts provide complete summary available evidence clinical decision makers use future investigations literature searches conducted using three databases relevant rcts nrsis according cochrane methodology abstract full texts retrieved manuscripts selected retrieved two investigators based prismaa guidelines risk bias quality evidence assessments performed outcome data weight appetite quality life performance status adverse effects mortality combined narrative synthesis metaanalysis possible ten studies included four rcts six nrsis matching eligibility criteria lowquality evidence metaanalysis suggested significant benefits cannabinoids appetite compared control standardized mean difference 002 95 confidence interval 051 046 p 093 patientreported observations nrsis suggested improvements appetite another metaanalysis moderate quality evidence showed cannabinoids significantly less efficient active inactive control quality life standardized mean difference 025 95 confidence interval 043 007 p 0007 effectiveness cannabinoids alone improve outcomes cac remains unclear lowquality evidence rcts nrsis shows significant benefits cannabinoids weight gain appetite stimulation better quality life three important outcomes cachexia higher quality research integrating cannabinoids multimodal therapies may offer better opportunities developing cacspecific treatments review also highlights findings nonrandomized studies interventions nrsis can provide evidence effects intervention advocate feasibility larger rctspmid34881518 doi101002 jcsm12861,0.0
whole gut virome analysis 476 japanese revealed link phage autoimmune disease ann rheum dis 2021 dec 8annrheumdis2021221267 doi 101136 annrheumdis2021221267 online ahead printabstractobjective relationship autoimmune diseases gut microbiome intensively studied several autoimmunityassociated bacterial taxa identified however much less known roles gut virome autoimmune diseasesmethods performed whole gut virome analysis based shotgun sequencing 476 japanese included patients rheumatoid arthritis ra systemic lupus erythematosus sle multiple sclerosis healthy control subjectsresults casecontrol comparison viral abundance revealed crasslike phages one main components healthy gut virome significantly decreased gut patients autoimmune disease specifically patients ra sle addition podoviridae significantly decreased gut patients sle understand viruses affected bacteriome performed quantitative virusbacterium association analysis clustered regularly interspaced short palindromic repeatbased virusbacterium interaction analysis identified symbiosis podoviridae faecalibacterium addition multiple bacterial targets crasslike phages identified eg ruminococcus spp conclusion data suggest gut virome can affect body either directly via bacteria analyses elucidated previously missing part autoimmunityassociated gut microbiome presented new candidates contribute development autoimmune diseasespmid34880054 doi101136 annrheumdis2021221267,0.0
sixth nerve palsy children etiology longterm course diagnostic algorithm j child neurol 2021 dec 88830738211035912 doi 101177 08830738211035912 online ahead printabstractbackground acute onset strabismus worrisome parents physicians condition sometimes attributed sixth cranial nerve palsy may secondary various etiologies debate still exists appropriate diagnostic approachobjective objective study describe common etiologies sixth nerve palsy pediatric population suggest clear implementable diagnostic algorithmmethods authors conducted electronic medical review files patients admitted pediatric department emek medical center january 2014 april 2020 reviewed medical records study period patients following diagnoses according international classification diseases 9 sixth nerve palsy acute infective polyneuritis guillainbarr syndrome benign intracranial hypertension malignant neoplasm brain strabismus myasthenia gravis multiple sclerosis authors extracted information regarding clinical presentation previous history diagnostic workup including serological testing cerebrospinal fluid testing neuroimaging final diagnosis clinical followup assessedresults seventeen patients sixth nerve palsy identified common etiologies increased intracranial hypertension antigq1b syndrome 3 patients conclusions retrospective study patients diagnosed one medical center suggested algorithm validated prospective study etiologies sixth nerve palsy children variable authors suggest performing neuroimaging patients considering serum cerebrospinal fluid testing selected patients initial neuroimaging combined laboratory testing useful provides rational tools proper diagnosispmid34879720 doi101177 08830738211035912,0.0
reading quot tquot leaves covid19 vaccine responses multiple sclerosis neurology 2021 dec 8101212 wnl0000000000013166 doi 101212 wnl0000000000013166 online ahead printno abstractpmid34880090 doi101212 wnl0000000000013166,0.0
association time spent outdoors risk multiple sclerosis neurology 2021 dec 8101212 wnl0000000000013045 doi 101212 wnl0000000000013045 online ahead printabstractobjective study aims determine contributions sun exposure ultraviolet radiation uvr exposure risk paediatriconset multiple sclerosis ms methods children ms controls recruited multiple centres usa matched sex age multivariable conditional logistic regression used investigate association time spent outdoors daily summer use sun protection ambient summer uvr dose year prior birth year prior diagnosis ms risk adjusting sex age race birth season childs skin colour mothers education tobacco smoke exposure overweight epsteinbarr virus infectionresults 332 children ms median disease duration 73 months 534 controls included matching sex age fully adjusted model compared spending 30 minutes outdoors daily recent summer greater time spent outdoors associated marked reduction odds developing ms evidence doseresponse 30 minutes 1 hour adjusted odds ratio aor 048 95 confidence interval 95ci 023099 p005 12 hours aor019 95ci 009040 p0001 higher summer ambient uvr dose also protective ms aor076 per kj m2 95ci 062094 p001 conclusions causal association spending time sun summer may strongly protective developing paediatric ms well residing sunnier locationpmid34880094 doi101212 wnl0000000000013045,0.0
white matter microglia heterogeneity cns acta neuropathol 2021 dec 8 doi 101007 s0040102102389x online ahead printabstractmicroglia resident myeloid cells central nervous system cns play critical roles shaping brain development responding invading pathogens clearing tissue debris aberrant protein aggregations ageing neurodegeneration original concept like macrophages microglia either damaging proinflammatory regenerative antiinflammatory updated kaleidoscope view microglia phenotypes reflecting wideranging roles maintaining homeostasis cns contribution cns diseases well aiding repair use new technologies including single cell nucleus rna sequencing led identification many novel microglia states allowing better understanding complexity distinguishing regional variations cns also revealed differences species diseases microglia myeloid cells cns however data microglia heterogeneity generated cells isolated cortex whole brain whereas white matter changes differences white grey matter relatively understudied considering importance microglia regulating white matter health provide brief update current knowledge microglia heterogeneity white matter microglia important development cns microglial ageing affects cns white matter homeostasis discuss microglia intricately linked classical white matter diseases multiple sclerosis genetic white matter diseases putative roles neurodegenerative diseases white matter also affected understanding wide variety microglial functions white matter may provide basis microglial targeted therapies cns diseasespmid34878590 doi101007 s0040102102389x,0.0
mass spectrometry analysis human tear fluid biomarkers specificfor ocular systemic diseases context 3p medicine epma j 2021 dec 3127 doi 101007 s1316702100265y online ahead printabstractover last two decades large number noncommunicable chronic disorders reached epidemic level global scale diabetes mellitus type 2 cardiovascular disease several types malignancies neurological eye pathologiesall exerted systems enormous socioeconomic burden primary secondary tertiary healthcare paradigm change reactive predictive preventive personalized medicine 3pm pppm declared essential transformation overall healthcare approach benefit patient society large end specific biomarker panels instrumental costeffective predictive approach individualized prevention treatments tailored person source biomarkers crucial specificity reliability diagnostic tests treatment targets furthermore diagnostic approach preferentially noninvasive increase availability biomaterial decrease risks potential complications well concomitant costs requirements clearly fulfilled tear fluid represents precious source biomarker panels welljustified principle sick eye sick body makes comprehensive tear fluid biomarker profiling highly relevant diagnostics eye pathologies also prediction prognosis treatment monitoring systemic diseases one prominent example sicca syndrome linked cascade severe complications include dry eye neurologic oncologic diseases review protein profiles tear fluid highlighted corresponding biomarkers exemplified several relevant pathologies including dry eye disease diabetic retinopathy cancers neurological disorders corresponding analytical approaches sample preprocessing differential proteomics electrophoretic techniques highperformance liquid chromatography hplc enzymelinked immunosorbent assay elisa microarrays mass spectrometry ms methodology detailed consequently proposed overall strategies based tear fluid biomarkers application 3p medicine practice context 3p medicine tear fluid analytical pathways considered predict disease development target preventive measures create treatment algorithms tailored individual patient profilespmid34876936 pmcpmc8639411 doi101007 s1316702100265y,0.0
hladqa10401 related higher multiple sclerosis lesion load t2 flair mri sequences arq neuropsiquiatr 2021 dec 3s0004282x2021005026202 doi 101590 0004282xanp20200487 online ahead printabstractbackground genetic predisposition multiple sclerosis ms associated hla alleles especially hladrb11501objective identify associations findings magnetic resonance imaging mri genetic features brazilian cohort patients msmethods retrospectively studied data 95 consecutive patients ms two independent observers blinded clinical data identified black holes enhanced lesions t1 mri sequences counted measured contrastenhanced lesions t2 flair fluid attenuation inversion recovery sequences cases classified according lesion size number volume hladrb1 hladqb1 hladqa1 alleles rs4774 rs3087456 rs6897932 rs731236 rs1033182 single nucleotide polymorphisms identified polymerase chain reaction amplification sequencespecific primers using one lambda inc kit canoga park ca usaresults patients hladqa10401 allele lesion load adjusted age sex ms duration median compared patients hladqa1 alleles p002 differences among hla alleles single nucleotide polymorphisms lesion loadconclusions correlation hladqa10401 allele higher lesion load t2 flair mri sequences suggests presence allele associated risk greater ms severitypmid34877984 doi101590 0004282xanp20200487,0.0
spinal cord atrophy predicts progressive disease relapsing multiple sclerosis ann neurol 2021 dec 8 doi 101002 ana26281 online ahead printabstractobjective major challenge multiple sclerosis ms research understanding silent progression progressive ms using novel method accurately capture upper cervical cord area legacy brain mri scans aimed study role spinal cord brain atrophy silent progression conversion secondary progressive disease spms methods singlecenter observational study rrms n360 spms n47 patients 80 matched controls evaluated rrms patient subsets converted spms n54 silently progressed n159 respectively 12year observation period compared clinically matched rrms patients remaining rrms n54 stable n147 respectively brain mri assessed value brain spinal cord measures predict silent progression spms conversionresults patients developed spms showed faster cord atrophy rates 219 year least four years conversion compared rrms matches 088 year p0001 spinal cord atrophy rates decelerated conversion 163 year p0010 towards spms patients study entry 104 1 faster spinal cord atrophy rate associated 69 p00001 53 p00001 shorter time silent progression spms conversion respectivelyinterpretation silent progression conversion secondary progressive disease predominantly related cervical cord atrophy atrophy often present earliest disease stages predicts speed silent progression conversion progressive ms diagnosis spms rather late recognition neurodegenerative process distinct disease phase article protected copyright rights reservedpmid34878197 doi101002 ana26281,0.0
lactose casein cause changes biomarkers oxidative damage dysbiosis experimental model multiple sclerosis cns neurol disord drug targets 2021 dec 6 doi 102174 1871527320666211207101113 online ahead printabstractbackground objectives experimental autoimmune encephalomyelitis eae rats closely reproduces multiple sclerosis ms disease characterized neuroinflammation oxidative stress also appears extend organ compartments origin ms matter discussion seem altering certain bacterial populations present gut may lead proinflammatory condition due bacterial lipopolysaccharides lps socalled braingut axis casein lactose milk confer antiinflammatory properties immunomodulatory effects objectives study evaluate effects administration casein lactose oxidative damage clinical status caused eae verify whether casein lactose effect lps transport protein lbpmethods twenty male dark agouti rats divided control rats control eae rats eae rats casein lactose eae+casein eae+lactose respectively administered fiftyone days casein lactose administration rats sacrificed different organs studied brain spinal cord blood heart liver kidney small large intestine latter products derived oxidative stress studied lipid peroxides carbonylated proteins well glutathione redox system various inflammation factors total nitrite nuclear factorkappa b p065 rat tumour necrosis factor lps lbp valuesresults conclusion casein lactose administration improved clinical aspect disease time reducing inflammation oxidative stress exerting action glutathione redox system increasing gpx levelspmid34875994 doi102174 1871527320666211207101113,0.0
spatial patterns brain lesions assessed covariance estimations lesional voxels multiple sclerosis spacems technique neuroimage clin 2021 dec 2 33102904 doi 101016 jnicl2021102904 online ahead printabstractpredicting disability progressive multiple sclerosis ms extremely challenging although evidence spatial distribution white matter wm lesions may play role disability accumulation lack wellestablished quantitative metrics characterise aspects ms pathology makes difficult assess relevance clinical progression study introduces novel approach called spacems quantitatively characterise spatial distributional features brain ms lesions can assessed predictors disability accumulation spacems covariance matrix spatial positions patients lesional voxels computed eigenvalues extracted combined derive rotationallyinvariant metrics known common robust descriptors ellipsoid shape anisotropy planarity sphericity additionally spacems metrics include neuraxis caudality index defined wholebrain lesion mask well caudal brain lesion indicate distant supplementary motor cortex along neuraxis wholebrain mask caudal brain lesions applied spacems data 515 patients involved three studies mssmart nct01910259 msstat1 nct00647348 secondary progressive ms trials observational study primary secondary progressive ms patients assessed motor cognitive disability scales underwent structural brain mri 15 30 t baseline 2 years mri protocol included 3dt1weighted 1x1x1mm3 2dt2weighted 1x1x3mm3 anatomical imaging wm lesions semiautomatically segmented t2weighted scans deriving wholebrain lesion masks coregistering masks t1 images spacems metrics calculated analysed series multiple linear regression models built assess ability spatial distributional metrics explain concurrent future disability adjusting confounders patients whose wm lesions laid caudally along neuraxis isotropically distributed brain ie wholebrain lesion masks displaying high sphericity index baseline greater motor cognitive disability baseline time independently brain lesion load atrophy measures conclusion introduced spacems approach showed able capture clinically relevant spatial distributional features ms lesions independently sheer amount lesions brain tissue loss location lesions lower parts brain neurite density particularly high cerebellum brainstem greater spatial spreading lesions ie isotropic wholebrain lesion masks possibly reflecting higher number wm tracts involved associated clinical deterioration progressive ms usefulness spacems approach demonstrated ms may explored conditions also characterised presence brain wm lesionspmid34875458 doi101016 jnicl2021102904,0.0
effect natalizumab treatment rate evidence disease activity young adults multiple sclerosis relation pubertal stage j neurol sci 2021 nov 27 432120074 doi 101016 jjns2021120074 online ahead printabstractapproximately 40 youngonset multiple sclerosis ms patients experience breakthrough disease carries high risk longterm disability requires using therapies beyond traditional firstline agents despite increasing use newer diseasemodifying treatments dmts population data available guide need escalating dmts scarcity data effects natalizumab children young adults active disease performed retrospective analysis rate evidence disease activity neda tolerability safety natalizumab multicenter cohort 36 children young adults highly active ms patients active disease initiated treatment natalizumab primary endpoint rate achieving neda3 status within two years natalizumab treatment examine possible effect age outcome treatment outcomes also analyzed prepubertal n 13 children aged 913 years pubertal subgroups n 23 young adolescents aged 1420 years neda3 status prepubertal group 92 first second year pubertal group 96 first year 92 second year natalizumab reduced number volume brain lesions prepubertal pubertal groups treatment welltolerated 8 patients 222 adverse events 2year study period analysis shows natalizumab effective welltolerated prepubertal pubertal ms patientspmid34875473 doi101016 jjns2021120074,0.0
clinical perspective clinical outcome assessments neurosarcoidosis mult scler relat disord 2021 nov 15 57103403 doi 101016 jmsard2021103403 online ahead printabstractbackground validated clinical outcome assessments coas used neurosarcoidosisobjective surveyed clinicians treat patients neurosarcoidosis determine 1 current approaches assessment neurologic impairment 2 clinicians needs regarding future coa developmentmethods physician contacts foundation sarcoidosis research neurosarcoidosis consortium group sent online surveyresults 43 143 responders coas used minority settings apart time administration biggest barriers implementation lack validated diseasespecific measuresconclusions lack validated diseasespecific measures barrier monitoring neurological impairment neurosarcoidosispmid34875486 doi101016 jmsard2021103403,0.0
stemlike intestinal th17 cells give rise pathogenic effector tcells autoimmunity cell 2021 nov 30s00928674 21 013337 doi 101016 jcell202111018 online ahead printabstractwhile intestinal th17 cells critical maintaining tissue homeostasis recent studies implicated roles development extraintestinal autoimmune diseases including multiple sclerosis however mechanisms tissue th17 cells mediate dichotomous functions remain unknown characterized heterogeneity plasticity migratory phenotypes tissue th17 cells vivo combined fate mapping profiling transcriptomes tcr clonotypes 84 000 th17 cells homeostasis cns autoimmune inflammation inter intraorgan singlecell analyses revealed homeostatic stemlike tcf1+ il17+ slamf6+ population traffics intestine maintained microbiota providing ready reservoir il23driven generation encephalitogenic gmcsf+ ifn+ cxcr6+ t cells study defines direct vivo relationship il17+ nonpathogenic gmcsf+ ifn+ pathogenic th17 populations provides mechanism homeostatic intestinal th17 cells direct extraintestinal autoimmune diseasepmid34875227 doi101016 jcell202111018,0.0
analysing effect robotic gait lower extremity muscles classification using deep learning comput methods biomech biomed engin 2021 dec 7120 doi 101080 1025584220212012655 online ahead printabstractrobotic gait training helps nervous system recover strengthen weak muscle groups many studies literature show applying robotic gait rehabilitation patients neurological disorders multiple sclerosis ms stroke spinal cord injection sci effectively restores gait ability contrast studies literature included healthy individuals control patient groups formed detailed analyses carried groups study emg signals gma gme ilp bf vm mg ta muscles recorded simultaneously different electrode placement robotic gait first time literature location prevents phase shift presented classification performance also increased removing 26 different attribute parameters like time frequency statistics signals instead gait studies maximum 1216 traits extraction extracted features classified approaches multilayer perceptron neural networks mlp support vector machines svm knearest neighbourhood algorithm knn random forest classification algorithm rf deep learning detailed performance comparison realized among approaches compared stochastic gradient optimization algorithmbased deep learning structure produced best performance 985714 accuracy also seen essential plan exoskeleton robotic gait pattern suitable patients disease state muscle activationpmid34874210 doi101080 1025584220212012655,1.0
pet imaging reactive astrocytes neurological disorders eur j nucl med mol imaging 2021 dec 7 doi 101007 s00259021056405 online ahead printabstractthe reactive astrocytes manifest molecular structural functional remodeling injury infection diseases cns play critical role pathological mechanism neurological diseases growing need exists dependable approach better characterize activation astrocyte vivo advanced molecular imaging technology positron emission tomography pet potential visualizing biological activities cellular levels review summarized pet visualization strategies reactive astrocytes discussed applications astrocyte pet imaging neurological diseases future studies needed pay attention development specific imaging agents astrocytes improve exploration reactive astrocytes various diseasespmid34873637 doi101007 s00259021056405,0.0
pembrolizumab treatment inflammatory progressive multifocal leukoencephalopathy report two cases j neurovirol 2021 dec 7 doi 101007 s13365021010281 online ahead printabstractprogressive multifocal leukoencephalopathy pml rare devastating neurological disease caused reactivation jc virus susceptible individuals illness classically associated human immunodeficiency virus hiv multiple sclerosis ms patients treated natalizumab also associated haematological malignancies organ transplantation autoimmune disease immunodeficiency aside natalizumab range immunomodulators including obinutuzumab rituximab associated pml nature associations unclear due overall low incidence pml associated drugs fact patients will confounding risk factors developing disease known effective treatment available pml nonhiv nonms cohort recent case studies series proposed pembrolizumab antipd1 immune checkpoint inhibitor may potentially efficacious option patients present two cases nonhiv nonms patients pml treated pembrolizumab little clinical benefit literature surrounding pembrolizumab use pml discussed focus potential indicators successful outcomes patients receive therapypmid34874539 doi101007 s13365021010281,0.0
disrupted cognitive development following pediatric acquired demyelinating syndromes longitudinal study child neuropsychol 2021 dec 6122 doi 101080 0929704920212002289 online ahead printabstractlongterm cognitive deficits observed children experience acquired demyelinating syndrome ads examined changes cognitive functioning first two years following incident ads andtested whether normalized brain thalamic volume accounted decline time twentyfive youth mean age 128 years ads 9 diagnosed multiple sclerosis ms 16 experienced monophasic ads monoads underwent two neuropsychological evaluationsand mri scans approximately6 24months post adsonset examined changes cognitive outcomes time patient groups generalized linear mixedeffect regression models used examine association normalized brain thalamic volumesbetween two timepointswith cognitive zscores cognitive performance within ageexpected range groups remained stable time 15 measures combined sample monoads ms patients declines p 05 noted symbol digit modalities test sdmt auditory working memory awm wjiii visual matching vismat tests survive fdr correction clinically significant declines measured reliable change index observed sdmt awm vismattests 19 42 32 respectively lower normalized brain volume 6months predicted negative change sdmt b 045 95ci 007 083 awm b 030 95ci 013 047 chronicity demyelination required cognitive decline reduced brain volume suggesting even single demyelinating event may negatively impact cognitive potential childrenpmid34872458 doi101080 0929704920212002289,1.0
neuroretinitis associated multiple sclerosis j neuroophthalmol 2021 oct 22 doi 101097 wno0000000000001374 online ahead printno abstractpmid34873139 doi101097 wno0000000000001374,0.0
waterpipe tobacco smoking multiple sclerosis environmental risk factors neuroepidemiology 2021 dec 6 doi 101159 000521223 online ahead printabstractintroduction number wellestablished risk factors multiple sclerosis ms factors however showed conflicting nonconsistent results examine factors unique practiced saudi arabia sa arab region waterpipe tobacco smoking wts face veiling raw milk rm camel milk cm consumption tuberculosis tb infection addition traditional factors methods sex age matched casecontrol study used structured questionnaire examine relation number factors exposures risk ms three hundred ms patients 601 controls included data analyzed across different statistical models using logistic regression adjusting age sex marital status duration breastfeeding age first joining school coffee consumption face exposure results cigarette smoking 179 95 ci 101317 p 0047 wts 225 95 ci 121415 p 0010 cm consumption 250 95 ci 120521 p 0014 increased risk ms performing hajj 047 95 ci 034067 p 0001 tb infection 029 95 ci 011078 p 0015 face veiling 032 95 ci 023047 p 0001 coffee consumption 067 95 ci 049089 p 0008 appeared associated decreased risk association found fast food processed meat soft drinks animal milk camel rm consumption risk ms conclusion results casecontrol study confirm different means tobacco smoking associated increased risk ms also sheds light complex association infections mspmid34872078 doi101159 000521223,0.0
nmdar1 autoantibodies amplify behavioral phenotypes genetic white matter inflammation mild encephalitis model neuropsychiatric relevance mol psychiatry 2021 dec 6 doi 101038 s41380021013928 online ahead printabstractencephalitis estimated prevalence 001 even extensive diagnostic workup infectious etiology identified suspected 50 cases suggesting role etiologically unclear noninfectious processes mild encephalitis runs frequently unnoticed despite slight neuroinflammation detectable postmortem many neuropsychiatric illnesses widely unexplored field humans though clearly documented rodents genetic brain inflammation particularly associated myelin abnormalities inducing primary white matter encephalitis hypothesized autoimmune encephalitides may result brain inflammation concurring presence brain antigendirected autoantibodies eg nmethyldaspartatereceptor nr1 nmdar1ab causal may considerably shape encephalitis phenotype therefore immunized young female cnp mice lacking structural myelin protein 23cyclic nucleotide 3phosphodiesterase cnp cocktail nmdar1 peptides cnp mice exhibit early lowgrade inflammation white matter tracts bloodbrain barrier disruption novel mentaltimetravel test disclosed cnp mice compromised whatwherewhen orientation episodic memory readout deteriorated nmdar1ab contrast comparing wildtype cnp mice without nmdar1ab regarding hippocampal learning memory motor balance coordination revealed distinct stair patterns behavioral pathology elucidate potential contribution oligodendroglial nmdar downregulation nmdar1ab effects generated conditional nr1 knockout mice mice displayed normal morris water maze mentaltimetravel beam balance performance similar immunized cnp immunohistochemistry confirmed neuroinflammation neurodegeneration cnp mice yet without addon effect nmdar1ab conclude genetic brain inflammation may explain encephalitic component underlying autoimmune conditionspmid34866134 doi101038 s41380021013928,1.0
local remote interactions macrophages microglia neurological conditions curr opin immunol 2021 dec 1 74118124 doi 101016 jcoi202111006 online ahead printabstractin central nervous system cns parenchymal macrophages called microglial cells distinct developmental origin can selfrenew however pathological conditions bloodbrainbarrier becomes leaky including injury multiple sclerosis glioblastoma monocytederived macrophages mdm infiltrate cns cohabit microglia neurodegenerative diseases alzheimers disease als mdm mostly enter cns instead microglia take several identities specific case als affected motor neurons even surrounded locally microglia along peripheral nerves mdmderived macrophages specific functions interactions different myeloid cells starting recognized hold high promise targeted therapiespmid34864338 doi101016 jcoi202111006,0.0
role il17 antiil17 agents immunopathogenesis management autoimmune inflammatory diseases int immunopharmacol 2021 dec 1108402 doi 101016 jintimp2021108402 online ahead printabstractinterleukin17 il17 proinflammatory cytokine involved chronic inflammation occurring pathogenesis allergy malignancy autoimmune diseases rheumatoid arthritis systemic lupus erythematosus multiple sclerosis psoriasis il17 produced multiple cell types adaptive innate immunity including t helper 17 cells cd8 + t cells t cells natural killer t cells innate lymphoid cells monoclonal antibodies mabs targeting il17 il17r potential approach study therapeutic tool diseases current review aimed highlight characteristics il17 important role pathogenesis related diseases critical evaluation mabs targeting il17a il17 receptors eg ixekizumab secukinumab brodalumab various immunemediated diseases will provided finally clinical efficacy safety will reportedpmid34863654 doi101016 jintimp2021108402,0.0
immune signature multiple sclerosisassociated depression brain behav immun 2021 dec 1s08891591 21 006255 doi 101016 jbbi202111022 online ahead printabstractmultiple neurobiological pathways implicated pathobiology major depressive disorder mdd identification reliable biological substrates across entire mdd spectrum however hampered vast heterogeneity clinical presentation presumably consequence heterogeneous pathobiology one way overcome limitation explore disease subtypes based biological similarity inflammatory depression subtype may particularly enriched depressed patients underlying inflammatory condition multiple sclerosis ms provide informative disease context approach studies explored immune markers msassociated depression replications missing address analyzed data two independent casecontrol studies immune signatures msassociated depression conducted two different academic ms centers overall sample size n132 using stepwise datadriven approach identified cd4+ccr7lowtcm cell frequencies robust correlate depression ms signature associated core symptoms depression depression severity ms severity per se linked neuroinflammation determined magnetic resonance imaging mri furthermore exploratory analyses t cell polarization revealed largely driven cells th1like phenotype findings suggest neuro immune pathways linked affective symptoms autoimmune disorders ms potential relevance understanding inflammatory subtypes depressionpmid34863857 doi101016 jbbi202111022,0.0
survey clinical pipeline neuroscience bioorg med chem lett 2021 dec 2128482 doi 101016 jbmcl2021128482 online ahead printabstractmany new firstinclass drugs neuroscience indications introduced past decade including new treatments migraine amyotrophic lateral sclerosis depression multiple sclerosis however significant unmet patient needs remain areas chronic pain neurodegeneration psychiatric diseases epilepsy review summarizes advanced clinical compounds indications additionally current opportunities challenges remain respect genetic validation biomarkers translational models discussedpmid34864194 doi101016 jbmcl2021128482,0.0
mistaken identity many diagnoses frequently misattributed lyme disease j med 2021 nov 30s00029343 21 007920 doi 101016 jamjmed202110040 online ahead printabstractbackground prior studies demonstrated lyme disease frequently overdiagnosed however studies describe conditions misdiagnosed lyme diseasemethods retrospective observational cohort study evaluated patients referred lyme disease midatlantic academic center 20002013 lacked evidence borrelia burgdorferi infection primary outcome clinically described diagnoses contributing symptoms secondary outcomes included symptom duration determination whether diagnoses new attributed existing medical conditionsresults 1261 referred patients 1061 84 findings active lyme disease 690 65 receiving diagnoses resulting 405 59 newly diagnosed medical conditions 134 19 attributed preexisting medical issues 151 22 new preexisting conditions among 690 patients median symptom duration 796 days total 139 discrete diagnoses made infectious disease diagnoses comprised 32 leading diagnoses anxiety depression 222 21 fibromyalgia 120 11 chronic fatigue syndrome 77 7 migraine disorder 74 7 osteoarthritis 62 6 sleep disorder apnea 48 5 examples less frequent nonsyndromic diseases newly diagnosed included multiple sclerosis 11 malignancy 8 parkinsons disease 8 sarcoidosis 4 amyotrophic lateral sclerosis 4 conclusions patients longterm symptoms either new preexisting disorders accounting symptoms lyme disease suggesting overdiagnosis population patients referred consideration lyme disease chronic symptoms deserve careful assessment diagnoses borrelia burgdorferi infectionpmid34861197 doi101016 jamjmed202110040,0.0
development prognostic model predicting multiple sclerosis optic neuritis secondary analysis data optic neuritis treatment trial j neuroophthalmol 2021 oct 22 doi 101097 wno0000000000001424 online ahead printabstractbackground optic neuritis can initial manifestation multiple sclerosis ms purpose study develop prognostic model predicting risk ms development among patients optic neuritismethods data 388 patients optic neuritis retrieved optic neuritis treatment trial ontt cox proportional hazards regression analysis used develop prognostic model performance model assessed using harrells cindex calibration curves rates ms development estimated using kaplanmeier methodresults among enrolled subjects total 154 397 patients developed clinically definite ms median followup period 158 years interquartile range 72169 years factors associated development ms presence brain lesions baseline mri previous nonspecific neurologic symptoms commencing lowdose corticosteroids treatment ocular pain absence optic disc peripapillary hemorrhage incorporating 5 factors prognostic model cindex 072 95 confidence interval ci 069076 good calibration curves obtained cindex model significantly higher cindexes single factor p 0001 cases model able stratify ontt patient cohort 3 risk groups significantly different intergroup rates developing ms rates developing ms within 15year period highrisk group 757 95 ci 656829 intermediaterisk group 447 95 ci 314554 lowrisk group 208 95 ci 142268 logrank p 0001 conclusions prognostic model better prediction ability compared standard practice relies solely using brain lesions mri can therefore help guide decisionmaking initiate earlier diseasemodifying therapy patients optic neuritis risk developing mspmid34860745 doi101097 wno0000000000001424,0.0
immunogenicity safety mrna covid19 vaccines people multiple sclerosis treated different diseasemodifying therapies neurotherapeutics 2021 dec 3 doi 101007 s13311021011659 online ahead printabstractthe potential impact diseasemodifying therapies dmts multiple sclerosis ms covid19 vaccination poorly understood according recent observations humoral immune response impaired patients treated ocrelizumab fingolimod study evaluated immunogenicity safety mrna covid19 vaccines convenience sample 140 ms patients treated different dmts undergoing vaccination april june 2021 humoral immune response tested 1 month second dose using chemiluminescent microparticle immunoassay detect igg sarscov2 nucleoprotein explored potential correlation igg titer dmts patients treatment firstline dmts natalizumab cladribine alemtuzumab developed measurable humoral response patients treated ocrelizumab fingolimod igg level significantly lower patients 222 fingolimod 66 ocrelizumab failed develop measurable humoral response ocrelizumab group igg level positively correlated time last infusion sarscov2 infections reported vaccination reported side effects pain injection site 571 fatigue 379 patient experienced severe side effects requiring hospitalization study confirms covid19 vaccination safe welltolerated ms patients recommended patients regardless current dmts since fingolimod ocrelizumab reduce humoral immune response patients treated drugs detecting sarscov2 antibodies helpful monitor immune response vaccinationpmid34859382 doi101007 s13311021011659,0.0
regulation common neurological disorders gut microbial metabolites exp mol med 2021 dec 2 doi 101038 s1227602100703x online ahead printabstractthe gut connected cns immunological mediators lymphocytes neurotransmitters microbes microbial metabolites mounting body evidence indicates microbiome exerts significant effects immune cells cns cells effects frequently result suppression exacerbation inflammatory responses latter can lead severe tissue damage altered synapse formation disrupted maintenance cns herein review recent progress research microbial regulation cns diseases focus major gut microbial metabolites shortchain fatty acids tryptophan metabolites secondary bile acids pathological changes cns associated dysbiosis altered levels microbial metabolites can exacerbate various neurological disorders cellular molecular mechanisms gut microbial metabolites regulate inflammatory diseases cns discussed highlight similarities differences impact four major cns diseases ie multiple sclerosis parkinsons disease alzheimers disease autism spectrum disorder identify common cellular molecular networks governing regulation cellular constituents pathogenesis cns microbial metabolitespmid34857900 doi101038 s1227602100703x,0.0
marburg multiple sclerosis variant complete remission early administration mitoxantronea case report neurol ther 2021 dec 2 doi 101007 s40120021003086 online ahead printabstractmarburg variant severe fulminant pseudotumor form multiple sclerosis ms high morbidity mortality rates scarcity remains incompletely characterized physicians experiences will influence treatment report inflammatory explosive case 31yearold woman presenting rapid neurological degradation histology proven marburgs disease successfully treated early administration mitoxantrone mitx knowledge first case describing complete remission mitx biopsyproven conditionpmid34859363 doi101007 s40120021003086,1.0
preliminary analysis brain footprints multiple sclerosis females detrusor sphincter dyssynergia concurrent urodynamic functional magnetic resonance imaging study int neurourol j 2021 dec 2 doi 105213 inj2142012006 online ahead printabstractpurpose study evaluates grey white brain matter characteristics women multiple sclerosis ms detrusor sphincter dyssynergia dsd grey matter assessed via functional connectivity fc brain regions activated voiding using functional magnetic resonance imaging fmri two white matter tracts involved bladder function anterior thalamic radiation atr superior longitudinal fasciculus slf evaluated using diffusion tensor imaging dti methods twentyseven women ms two groups nodsd n23 dsd n4 eight healthy controls hc underwent concurrent urodynamicfmri evaluation four cycles bladder filling emptying fc similarity measure fc_sim calculated subject express similarity individual fc voiding initiation compared fc patterns atr slf tracts traced fractional anisotropy fa mean diffusivity md recordedresults mean fc_sim values significantly different among three groups indicating distinct fc patterns however significant difference found dsd nodsd groups dsd group showed trends lower fa higher md indicating loss coherence tracts compared hcs left right atr compared ms women neither dsd voiding dysfunction vd suggesting damage tracts ms women dsdconclusions women ms show distinctly different fc patterns compared hcs trends showing damage atr women ms dsd compared neither dsd vdpmid34856727 doi105213 inj2142012006,0.0
adrenal crisis presenting recurrent encephalopathy mimicking autoimmune infectious encephalitis common variable immune deficiency case report neurologist 2021 nov 30 doi 101097 nrl0000000000000374 online ahead printabstractintroduction adrenal crisis can present lifethreatening complications mimic autoimmune infectious encephalitis common variable immune deficiency cvid literature regarding neurological complications adrenal crisis limited focuses patients present hypotension electrolyte abnormalitiescase report 30yearold man presented 3 times hospital encephalopathy fever left sided weakness history multiple autoimmune diseases prior hospitalizations encephalopathy first 2 admissions normotensive without electrolyte abnormalities extensive workup infectious paraneoplastic seizure metabolic toxic vascular etiologies autoimmune encephalitis negative exam returned baseline empiric steroid treatment discharged represented 2 months later encephalopathy third admission subsequent presentation hyponatremia low serum osmolality elevated urine sodium undetectable morning cortisol 21 hydroxylase autoantibodies diagnosis autoimmune adrenal insufficiency established treated physiological doses hydrocortisone fludrocortisone improved rapidly near baseline function remained relapsefree 4year follow admissions also found low immunoglobulin g levels met criteria cvid however immunoglobin levels recovered steroid replacementconclusion reported patient demonstrated neurological complications adrenal crisis can mimic autoimmune conditions cvid neurologist aware recurrent encephalopathy adrenal insufficiency can occur regardless hemodynamic electrolyte changes typical hospital metabolic panelspmid34855666 doi101097 nrl0000000000000374,0.0
antigenpresenting innate lymphoid cells orchestrate neuroinflammation nature 2021 dec 1 doi 101038 s41586021041364 online ahead printabstractproinflammatory t cells central nervous system cns causally associated multiple demyelinating neurodegenerative diseases16 pathways control responses remain unclear define population inflammatory group 3 innate lymphoid cells ilc3s infiltrate cns mouse model multiple sclerosis ilc3s derived circulation localize proximity infiltrating t cells cns function antigenpresenting cells restimulate myelinspecific t cells increased individuals multiple sclerosis notably antigen presentation inflammatory ilc3s required promote t cell responses cns development multiplesclerosislike disease mouse models contrast conventional tissueresident ilc3s periphery appear contribute disease induction instead limit autoimmune t cell responses prevent multiplesclerosislike disease experimentally targeted present myelin antigen collectively data define population inflammatory ilc3s essential directly promoting tcelldependent neuroinflammation cns reveal potential harnessing peripheral tissueresident ilc3s prevention autoimmune diseasepmid34853467 doi101038 s41586021041364,1.0
validation dyals dysphagia amyotrophic lateral sclerosis questionnaire evaluation dysphagia als patients neurol sci 2021 dec 1 doi 101007 s10072021057751 online ahead printabstractbackground dysphagia common symptom trajectory als can significantly impact quality life prognosis patients nowadays specific tool screening dysphagia als validated approach heterogeneous across italian centresobjective validate dyals dysphagia amyotrophic lateral sclerosis questionnaire adapting dymus dysphagia multiple sclerosis questionnaire assessment dysphagia als patients order uniform evaluations across italian als networkmethods included 197 patients diagnosed als following el escorial criteria sixteen italian als centres 1st december 2019 1st july 2020 patient collected clinical demographic data obtained alsfrsr score alsaq5 score dymus score eat10 scoreresults across 197 patients ratio m f 113 84 median age 64 years iqr 56725 bulbar patients 20 spinal patients 80 median alsfrsr total score patients 35 iqr 2839 dyals score statistically higher bulbar als spinal als median 6 iqr 459 vs median 1 iqr 05 z 6253 p 00001 dyals questionnaire showed high internal consistency cronbachs alpha 088 statistically significant correlation dyals eat10 rho 090 p 00001 conclusions dyals scale reliable manageable easily usable screening dysphagia als can shared italian als centres order collect uniform data therapeutic strategies clinical trialspmid34853898 doi101007 s10072021057751,0.0
microglia monocytes inflammatory cns disease integrating phenotype function acta neuropathol 2021 dec 1 doi 101007 s00401021023842 online ahead printabstractin neurological diseases actions microglia resident myeloid cells cns parenchyma may diverge intersect recruited monocytes drive immunemediated pathology however defining precise roles cell type historically impeded lack discriminating markers experimental systems capable accurately identifying ability distinguish microglia monocytes neuroinflammation advanced singlecell technologies new markers drugs identify deplete respectively nevertheless focus individual studies particular cell types diseases experimental approaches limited ability connect phenotype function widely across diverse cns pathologies critically review tabulate integrate diseasespecific functions immune profiles microglia monocytes provide comprehensive atlas myeloid responses viral encephalitis demyelination neurodegeneration ischemic injury emphasizing differential roles microglia monocytes severe neuroinflammatory disease viral encephalitis connect inflammatory pathways common equally incapacitating diseases less severe inflammation examine findings context human studies highlight benefits inherent limitations animal models may impede facilitate clinical translation enables us highlight common contrasting nonredundant often opposing roles microglia monocytes disease targeted therapeuticallypmid34853891 doi101007 s00401021023842,1.0
als patients concurrent neuroinflammatory disorders nationwide clinical records study amyotroph lateral scler frontotemporal degener 2021 jul 10111 doi 101080 2167842120211946084 online ahead printabstractobjectiveto determine inflammation proximity motor unit may contribute neurodegeneration amyotrophic lateral sclerosis als methods identified patients diagnosed sweden concurrent als multiple sclerosis ms myasthenia gravis mg inflammatory polyneuropathies ip dermatopolymyositis dmpm 19912014 according swedish patient register n 263 validated medical records 92 patients 18 records retrieved three contain enough information compared patients confirmed overlap n 28 independent sample patients solely als n 271 results ninetyone patients deemed als 346 among remaining 151 validated als 12 also confirmed ms diagnosis nine confirmed mg diagnosis four confirmed ip diagnosis three confirmed dmpm diagnosis seventeen patients women 11 men seventynine percent patients confirmed overlap ms mg ip dmpm diagnosed prior als compared patients als concurrent patients significantly older symptoms onset higher prevalence bulbar onset used riluzole noninvasive ventilation less frequently conclusions found high concurrence als ms mg ip dmpm diagnoses largely due diagnostic uncertainty minority patients true concurrence ms mg ip dmpm preceded als diagnosis might due chance alone four patients diagnosed mg shortly onset als suggesting neurodegeneration might trigger autoimmunitypmid34852680 doi101080 2167842120211946084,0.0
detection ataxia hybrid convolutional neural network using static plantar pressure distribution model patients multiple sclerosis comput methods programs biomed 2021 nov 17 214106525 doi 101016 jcmpb2021106525 online ahead printabstractobjective study aimed detect ataxia persons multiple sclerosis pwms deep learningbased approach using image dataset containing static plantar pressure distribution alternative objective method will proposed assist physicians diagnose pwms early stagesmethods total 406 static bipedal pressure distribution image data 43 ataxic pwms 62 healthy individuals used study preprocessing images given input pretrained deep learning models vgg16 vgg19 resnet densenet mobilenet nasnetmobile data model utilized generate feature vectors finally feature vectors obtained static pressure distribution images classified svm support vector machine knn knearest neighbors ann artificial neural network addition crossvalidation method used examine validity classifierresults performance proposed models evaluated accuracy sensitivity specificity f1measure criteria vgg19svm hybrid model showed best performance 9512 acc 9491 sen 9531 spe 9444 f1conclusions study specific sensitive automatic test evaluation system proposed ataxic syndromes using digital images observe motor skills subjects comparative results show proposed method can applied practice ataxia clinically difficult detect yet symptomatic can defined using static plantar pressure distribution early stage can recommended assistant system physicians clinical practicepmid34852958 doi101016 jcmpb2021106525,0.0
mitochondrial dysfunction trigger programmed axon death trends neurosci 2021 nov 29s01662236 21 002149 doi 101016 jtins202110014 online ahead printabstractmitochondrial failure long associated programmed axon death wallerian degeneration wd widespread potentially preventable mechanism axon degeneration early findings axotomised axons indicated mitochondria involved execution steps pathway recent studies suggest addition mitochondrial dysfunction can initiate programmed axon death without physical injury mitochondrial dysfunction associated disorders involving early axon loss including parkinsons disease peripheral neuropathies multiple sclerosis findings programmed axon death activated mitochondrial impairment indicate involvement druggable mechanisms whose disruption may protect axons diseases review latest developments linking mitochondrial dysfunction programmed axon death discuss implications injury diseasepmid34852932 doi101016 jtins202110014,0.0
brief international cognitive assessment multiple sclerosis bicams discrete regressionbased norms brazilian context arq neuropsiquiatr 2021 nov 29s0004282x2021005025202 doi 101590 0004282xanp20200526 online ahead printabstractbackground brief international cognitive assessment multiple sclerosis bicams recently developed brief practical feasible tool cognitive impairment multiple sclerosis ms objective study aimed provide continuous discrete normative values bicams brazilian contextmethods normatization achieved using six hundred one healthy controls community assessed five brazilian geopolitical regionsresults mean raw scores t scores percentiles z scores bicams measure provided stratified age educational level regressionbased norms provided converting raw scores scaled scores regressed age gender education yielding equations can used calculate predicted scores regression analyses revealed age gender education significantly influenced test results previous studiesconclusions normative data bicams brazilian context presented good representativeness improving use daily clinical practicepmid34852072 doi101590 0004282xanp20200526,0.0
paramagnetic rim lesions multiple sclerosis comparison visualization 15t 3t mri ajr j roentgenol 2021 dec 1 doi 102214 ajr2126777 online ahead printabstractbackground multiple sclerosis ms characterized acute chronic intrathecal inflammation subset ms lesions show paramagnetic rims susceptibilityweighted mri sequences reflecting iron accumulation microglia paramagnetic rim lesions prls proposed marker compartmentalized smoldering disease prls demonstrated 7 t recently 3 t susceptibility effects weaker lower field strength remains unclear prls visible 15 t objective compare visualization prls using susceptibilityweighted imaging 15t 3t mri patients ms methods retrospective study included 9 patients 5 women 4 men mean age 468 years ms underwent 15t 3t mri using comparable susceptibilityweighted sequence manufacturer ge swan lesions measuring 3 mm annotated two reviewers independently assessed images field strength separate sessions classifying annotated lesions based susceptibilityweighted images isointense diffusely paramagnetic prl discrepancies discussed consensus sessions including third reviewer agreement assessed using kappa coefficients results 140 annotated lesions based 3t consensus readings 115 82 isointense 16 11 diffusely paramagnetic 9 6 prls based 15t consensus readings 115 82 isointense 14 10 diffusely paramagnetic 11 8 prls mean lesion diameter 119 mm prls versus 64 mm diffusely paramagnetic lesions p006 78 mm isointense lesions p003 interrater agreement lesion classification prl substantial 15 t 065 3 t 070 agreement prl also substantial consensus readings two field strengths 079 conclusion show comparable identification prls 15t 3t mri substantial interrater agreement field strengths substantial consensus agreement field strengths clinical impact prl may emerging marker chronic neuroinflammation ms visibility 15 t supports translational potential prl identification widespread clinical settings 15t scanners prevalentpmid34851712 doi102214 ajr2126777,0.0
effects homebased virtual reality telerehabilitation system people multiple sclerosis randomized controlled trial j telemed telecare 2021 dec 11357633x211054839 doi 101177 1357633x211054839 online ahead printabstractbackground objective multiple sclerosis inflammatory neurodegenerative disorder central nervous system can lead severe motor disability aim study verify health care effects integrated telerehabilitation approach involving dualdomains motor cognitive people multiple sclerosis using virtual reality rehabilitation system compared homebased conventional rehabilitative intervention usual care patientrelevant outcomes motor cognitive participation methods multicentre interventional randomized controlled trial included 70 participants multiple sclerosis 35 telerehabilitation group 30 sessions homebased virtual reality rehabilitation system training five sessions week lasting 45 min 35 usual care group 30 sessions conventional treatment five sessions week participants completed assessment motor cognitive participation outcomes baseline 6 weeks treatmentresults total 633 telerehabilitation group exhibited improvement physical domain quality life p 0045 telerehabilitation group showed greater improvement usual care group minibestest domains balance p 0014 postural control p 0024 dynamic walking p 0020 posttreatment higher adherence registered telerehabilitation compared usual care 8667 vs 800 discussion study provides evidence people multiple sclerosis can benefit telerehabilitation treatment physical domain quality life motor symptoms moreover considering persistent covid19 emergency telerehabilitation can represent effective telemedicine solution safely delivering effective rehabilitation care people multiple sclerosistrial registration number trial register trial registered clinicaltrialsgov nct03444454 pmid34851211 doi101177 1357633x211054839,0.0
p038 ozanimod firstdose cardiac effects patients moderately severely active ulcerative colitis relapsing multiple sclerosis j gastroenterol 2021 dec 1 116 suppl 1 s9s10 doi 1014309 01ajg000079875272296f3no abstractpmid34848625 doi1014309 01ajg000079875272296f3,0.0
functional disability among systemic sclerosis patients relation disease characteristics quality life parameters curr rheumatol rev 2021 nov 30 doi 102174 1573397117666211130150241 online ahead printabstractbackground disability patients scleroderma ssc associated poor healthrelated quality life hrqol dimensions including physical psychological social dimensionsobjective study conducted examine different factors may associated functional disability poor hrqol aim targeting factors future improve physical activity functional outcomes hrqolmethods singlecenter crosssectional study conducted 38 patients ssc compare characteristics patients without disability using health assessment questionnaire disability index haqdi quality life assessed using short form36 sf36 linear regressions performed examine variables contributing functional disabilityresults almost 6578 n 25 patients study group reported functional disability presence functional disability associated reduced hrqol reflected physical function p 00001 physical role p 0016 bodily pain p 0001 general health p 0002 social functional p 0002 emotional role p 0042 mental health p 0025 domains sf36 score multiple linear regression indicated main predictive factors associated haqdi modified hand mobility scleroderma modified rodnan skin score distance walked 6 minutes borg dyspnea index saturation oxygen 6 minutes dibosa fatigue severity scale among patients sscconclusion patients ssc recognizing relationships clinical findings functional disability will allow development management strategies minimize disease severity enhance hrqolpmid34847844 doi102174 1573397117666211130150241,0.0
fastvelocity resistance training improves force development mobility multiple sclerosis int j sports med 2021 nov 30 doi 101055 a17101492 online ahead printabstractthis study aimed analyze benefits lowerlimb fastvelocity concentric resistance training rate force development mobility quality life people multiple sclerosis randomized controlled trial conducted 30 people multiple sclerosis randomly assigned either experimental n18 control n12 group experimental group carried 10weeks fastvelocity concentric resistance training control group perform intervention early late rate force development knee extension legs sittostand timed go tests quality life questionnaire evaluated intervention training program evoked increase early rate force development experimental group 030 rightleg 639 p0001 es14 leftleg 527 p0001 es10 compared control group showed modest increases furthermore experimental group improved mobility training sittostand 222 p0001 es10 timed go test 101 p0001 es11 increased perception quality life training control showed changes fastvelocity concentric resistance training potential improve early rate force development mobility 10weeks training addition increase selfperceived quality life following training modality demonstrates promising results multiple sclerosis populationpmid34847589 doi101055 a17101492,0.0
lumbar spine intrathecal transplantation neural precursor cells promotes oligodendrocyte proliferation hot spots chronic demyelination brain pathol 2021 nov 29e13040 doi 101111 bpa13040 online ahead printabstractexperimental autoimmune encephalomyelitis eae basic reliable model used study clinical pathological hallmarks multiple sclerosis ms rodents several studies suggest neural precursor cells npcs significant research tool reporting transplanted npcs promising therapeutic approach treating neurological disorders ms main objective approach preclinical vivo scenario oligodendrogenesis npcs targeting main chronic demyelinated lumbosacral milieu eae via least invasive delivery method lumbar puncture utilized mog3555 peptide induce eae c57bl 6 mice prior acute relapse intervened either traceable gfp+ cellular therapy saline solution intrathecal space lumbar spine brdu injection enabled us monitor endogenous proliferation marked endpoint 50 days postinduction 50 dpi neuropathology highthroughput triple immunofluorescent transmission electron microscopy tem data extracted analyzed experimental treatment attenuated chronic phase eae 50 dpi score 1 following acute clinical relapse myelination axonal integrity rescued npctreated animals along suppressed immune populations differentiation profile exogenous npcs endogenous brdu+ cells locationdependent gfp+ rich areas drove undifferentiated phenotypes toward oligodendrocyte lineage situ oligodendrocyte enrichment demonstrated increased p 0001 gap junction channels cx32 cx47 reliable markers proliferative oligodendroglia syncytium tem morphometric analysis ultimately manifested increased gratio lumbosacral fibers recovered animals p 0001 herein suggest single lumbar intrathecal administration npcs capacitated viable cellular load resulted clinical pathological amelioration stimulating resident opcs overcome remyelination failure eae demyelinating localepmid34845781 doi101111 bpa13040,0.0
mri transcallosal white matter helps predict motor impairment multiple sclerosis radiology 2021 nov 30210922 doi 101148 radiol2021210922 online ahead printabstractbackground altered callosal integrity associated motor deficits patients multiple sclerosis ms contribution disability knowledge authors investigated using multiparametric mri approaches purpose investigate structural functional interhemispheric mri substrates global disability different milestones upper limb motor impairment ms materials methods crosssectional study healthy control patients patients ms january 1 2008 december 31 2016 retrospectively selected hospital database clinical assessment included expanded disability status scale edss ninehole peg test digital finger tapping test using structural restingstate functional mri sequences probabilistic tractography hand corticospinal tract fibers transcallosal fibers handmotor cortices hereafter referred handm1 supplementary motor areas smas premotor cortices pmcs voxelmirror homotopic connectivity vmhc analyzed random forest analyses identified mri predictors clinical disability different milestones edss scores 30 40 60 upper limb motor impairment ninehole peg test finger tapping test z scores healthy control patients 5th percentile results onehundred thirty healthy control patients median age 39 years interquartile range 3150 years 70 women 340 patients ms median age 43 years interquartile range 3351 years 213 women studied edss 30 predictors n 159 global measures atrophy lesions together damage measures corticospinal tracts transcallosal fibers pmcs smas accuracy 86 p 00101 edss 40 n 131 similar predictors found addition damage transcallosal fibers handm1 accuracy 89 p 001049 mri predictors found edss 60 n 70 ninehole peg test right n 161 left n 166 finger tapping test right n 117 left n 111 impairments predicted damage transcallosal fibers smas pmcs accuracy range 6977 p 001049 vmhc abnormalities explain clinical outcomes conclusion structural functional abnormalities mri transcallosal premotor motor white matter fibers predicted severity global disability upper limb motor impairment patients multiple sclerosis informative role predictors appeared less evident higher disability levels rsna 2021 online supplemental material available article see also editorial barkhof pontillo issuepmid34846201 doi101148 radiol2021210922,0.0
pharmacotherapy cerebellar vestibular disorders curr opin neurol 2021 nov 29 doi 101097 wco0000000000001015 online ahead printabstractpurpose review major therapeutic advances made patients episodic progressive cerebellar ataxias downbeat nystagmus vestibular disorders provide update review subject highlighting important research findings last two yearsrecent findings recently use omaveloxolone 2 years significantly improved upright stability friedreichs ataxia patients openlabel study nacetyllleucine administered 6weeks significantly improved clinical impression change ataxia quality life patients niemannpick disease type c1 12week treatment dalfampridine associated improved standing balance subgroup patients multiple sclerosis glutenfree diet alone improved ataxia half patients antiglutamic acid decarboxylase gad ataxia suggesting gluten sensitivity might part underlying pathogenesis antigad ataxia headtohead trial prolongedrelease 4aminopyridine 4ap acetazolamide effectively reduced attacks 60 patients episodic ataxia type 2 ea2 albeit 4ap fewer adverse effects small observational studies shown patients episodic vestibular syndrome diagnosed definite probable vestibular migraine might still improve vestibular symptoms following preventive treatment migraine use vitamin d supplementation benign paroxysmal positional vertigo steroids acute unilateral vestibulopathy betahistine mnires disease patients remains controversialsummary although use several therapies established treatment cerebellar vestibular disorders urgent need prospective controlled therapeutic trialspmid34845147 doi101097 wco0000000000001015,0.0
efficacy safety therapeutic use cannabis derivatives synthetic analogs overview systematic reviews phytother res 2021 nov 29 doi 101002 ptr7263 online ahead printabstractthe debate use cannabinoids therapeutic purposes constantly rise overview aimed map evidence therapeutic effects cannabis derivatives synthetic analogs systematic reviews srs randomized trials identified comprehensive search several databases methodological quality evaluated amstar2 results main outcomes presented prioritizing updated better quality srs finally 68 srs addressing 37 different health conditions included methodological quality high eight srs evidence certainty grade effects cannabinoids high outcomes identified evidence certainty moderate following cannabidiol appears beneficial quality life increases risk adverse events ulcerative colitis b cannabinoids general appear clinically important benefit chronic nononcologic pain spasticityrelated pain multiple sclerosis acute postoperative pain c cannabinoids general appear benefit reducing chemotherapyrelated nausea vomiting outcomes remaining comparisons evidence certainty low low evaluated prevents recommendations routine usepmid34841610 doi101002 ptr7263,0.0
impact ramadan fasting disease activity patients multiple sclerosis multicenter study nutr neurosci 2021 nov 28110 doi 101080 1028415x20212006955 online ahead printabstractbackground safety ramadan fasting muslim patients suffering multiple sclerosis ms still matter debate work aimed study clinical course ms ramadan fasting clarify predictors relapses symptoms exacerbationmethods retrospective study included 153 muslim patients ms data related disease course ramadan obtained patients files whereas data related disease activity ramadan collected patients two months following ramadanresults patients ms experienced relapses exacerbation symptoms development new symptoms ramadan statistically significant longer disease duration compared experience p 0001 0001 001 respectively also patients experienced relapses exacerbation symptoms development new symptoms ramadan statistically significant higher expanded disability status scale edss compared experience p 0001 0001 001 respectively occurrence relapses exacerbation symptoms development new symptoms ramadan significantly higher patients experienced relapses preceding year compared p 0002 0002 001 respectively binary logistic regression revealed score elevation edss increased odds relapse ramadan 102 pvalue 004 also months increase disease duration increased odds relapse ramadan 187 pvalue 0046 conclusion high edss long disease duration independent predictors relapse ramadanpmid34842062 doi101080 1028415x20212006955,0.0
dimethyl fumarate potential therapeutic option alzheimer#39 s disease j alzheimers dis 2021 nov 21 doi 103233 jad215074 online ahead printabstractbackground dimethyl fumarate dmf approved clinical treatment multiple sclerosis based antioxidant antiinflammatory effects activating nrf2 pathway since oxidative stress inflammation involved alzheimers disease ad dmf potential therapeutic option adobjective study aims test therapeutic effects dmf ad model mice reveal underlying molecular mechanismsmethods cell viability assay vitro immunofluorescence imaging used evaluate antioxidant effect dmf embryonic mouse hippocampal neurons behavioral test brain magnetic resonance imaging used assess therapeutic effects dmf spatial learning memory well hippocampal volume ad model mice without nrf2 knockdown western blotting used analyze expression antioxidant enzymes molecules associated adrelated pathological pathwaysresults dmf inhibits reactive oxygen species overproduction protects neurons without nrf2 knockdown death dmf reduces amyloid induced memory impairment hippocampal atrophy ad model mice rather nrf2 knockdown ad mice dmf delays progression ad activating nrf2 pathway enhance expression downstream antioxidant enzymes inhibits lipid peroxidation apoptosis inflammation mitochondrial dysfunction amyloid depositionconclusion results indicate dmf potential therapeutic option ad antioxidant antiinflammatory antiapoptotic antiad effects activating nrf2 pathwaypmid34842188 doi103233 jad215074,0.0
crystallographic landscape provides molecular insights modes action diverse rort modulators drug discov today 2021 nov 24s13596446 21 005031 doi 101016 jdrudis202111022 online ahead printabstractrort master regulator th17 cells activated binding small molecules orthosteric site followed recruitment coactivators corepressors ligand binding domain lbd th17 cells provide immunedependent protection cancers pathogens dysregulation causes inflammation therefore implicated various autoimmune diseases multiple sclerosis rheumatoid arthritis psoriasis consequently enormous interest development rort modulators agonist inverseagonists review advances development rort modulators made past decade focusing rich crystallography landscape rort cocrystals delineated relationship binding patterns modulators resulting biological activitiespmid34838728 doi101016 jdrudis202111022,0.0
frailty falls people living multiple sclerosis arch phys med rehabil 2021 nov 24s00039993 21 015768 doi 101016 japmr202110025 online ahead printabstractobjective explore association frailty history falls people living multiple sclerosis ms design secondary analysissetting university research laboratories united states israelparticipants 118 people relapsingremitting ms age489 years sd100 746 female expanded disability status scale edss range1060 studied crosssectional analysisintervention applicablemain outcomes frailty index calculated 40 health deficits following standard validated procedures number falls 12month history recordedresults overall 339 297 364 participants classified nonfrail moderately frail severely frail respectively frailty index significantly correlated 037 p0001 higher scores edss univariable negative binomial regression analysis frailty index associated higher number falls irr333 95ci 185599 p0001 adjustment age gender edss frailty remained strongly associated history falls irr278 95ci 151510 p0001 conclusion current study identifies significant relationship frailty history falls ms independent age gender disease severity findings support notion frailty syndrome related independent disability mspmid34838587 doi101016 japmr202110025,0.0
contribution light development systemic sclerosis modulating il6 th1 chemokine expression dermal fibroblasts j invest dermatol 2021 nov 25s0022202x 21 025239 doi 101016 jjid202110028 online ahead printabstractsystemic sclerosis ssc autoimmune vascular disease resulting multiple organ fibrosis il6 th2 th17 cytokines serve critical disease drivers light proinflammatory cytokine promoting il6 production lung fibroblasts th1 chemokine expression dermal fibroblasts stimulated interferon ifn study investigated potential contribution light ssc development using clinical samples animal models sscinvolved skin light upregulated inflammatory cells hvem receptor light downregulated dermal fibroblasts similar expression profiles light hvem reproduced bleomycintreated mice transcription factor fli1 bound hvem promoter fli1 sirna suppressed hvem expression normal dermal fibroblasts ssc dermal fibroblasts light significantly increased il6 production ifn lightdependent th1 chemokine induction decreased compared normal dermal fibroblasts importantly light sirna significantly attenuated bleomycininduced skin fibrosis serum light levels elevated patients diffuse cutaneous ssc positively correlated clinical parameters reflecting skin pulmonary fibrosis taken together results suggest altered response dermal fibroblasts light namely increased il6 production decreased th1 chemokine expression contributes development skin fibrosis sscpmid34838790 doi101016 jjid202110028,0.0
emerging methods applications ultrahigh field mr spectroscopic imaging human brain anal biochem 2021 nov 24114479 doi 101016 jab2021114479 online ahead printabstractmagnetic resonance spectroscopic imaging mrsi brain enables insights metabolic changes fluxes diseases tumors multiple sclerosis epilepsy hepatic encephalopathy well insights general brain functionality however routine application mrsi mostly hampered low signaltonoise ratios snr due low concentrations metabolites 10000 times lower water furthermore mrsi spectra dense information content many overlapping metabolite resonances especially proton mrsi mri scanners ultrahigh field strengths like 7 t offer opportunity increase snr well separation resonances thus promising solve challenges yet mrsi ultrahigh field strengths challenged decreased b0 b1homogeneity shorter t2 relaxation times stronger chemical shift displacement errors aggravated lipid contamination therefore capitalize advantages ultrahigh field strengths challenges must overcome review focuses challenges mrsi human brain faces ultrahigh field strength well possible applications datepmid34838516 doi101016 jab2021114479,0.0
systematic review cases cns demyelination following covid19 vaccination j neuroimmunol 2021 nov 9 362577765 doi 101016 jjneuroim2021577765 online ahead printabstractbackground since emergency use approval different types covid19 vaccines several safety concerns raised regarding early delayed impact nervous systemobjective study aims systematically review reported cases cns demyelination association covid19 vaccination performed knowledgemethods systematic review performed screening published articles preprints cases cns demyelination association covid19 vaccines pubmed scopus embase google scholar ovid medrxiv databases september 30 2021 study followed prisma guidelines descriptive findings reported cases reviewed stratified demographic clinical findings diagnostic workup management overall outcomeresults total 32 cases identified female predominance 688 median age 44 years eleven cases reported pfizer vaccine 8 following astrazeneca vaccine 6 following moderna 5 following sinovac sinopharm vaccines one following sputnik johnsonjohnson vaccines majority cases 718 occurred first dose vaccine neurological symptoms manifesting median 9 days common reported presentations transverse myelitis 12 32 mslike pictures first diagnosis relapse another 12 32 cases followed adem like 5 32 nmosd like 3 32 presentations history previous immunemediated disease reported 17 32 531 cases mrnabased vaccines resulted greatest number demyelinating syndromes 17 32 followed viral vector vaccines 10 32 inactivated vaccines 5 32 mslike episodes 9 12 triggered mrnabased vaccines tm occurred following viral vector mrnabased vaccines management included high dose methylprednisolone plex ivig combination favorable outcome majority case marked complete improvement 25 32 stabilized partial recovery remaining casesconclusion systematic review identified cases cns demyelination following types approved covid19 vaccines far clinical presentation heterogenous mainly following first dose however half reported cases history immunemediated disease favorable outcome observed cases suggest longterm postmarketing surveillance cases assess causality ensure safety covid19 vaccinespmid34839149 doi101016 jjneuroim2021577765,1.0
insilico design peptides inhibition hlaa03klietyfsk complex new drug design treatment multiples sclerosis disease j mol graph model 2021 nov 16 111108079 doi 101016 jjmgm2021108079 online ahead printabstractmultiple sclerosis recognized chronic inflammatory disease human leukocyte antigen hla plays important role initiating adaptive immune responses hla class present almost nucleated cells presents cleaved endogenous peptide antigens cytotoxic t cells hlaa03 one hla class alleles reported substantially related hla ms disease 2011 structure hlaa03 complex identified immunodominant proteolipid protein plp epitope klietyfsk complex reported important autoantigenpresenting complex ms pathogenesis study new peptides designed bind complex may prevent specific pathogenic cytotoxic t cell binding autoantigenpresenting complex cns demyelination herein 14 new helical peptides containing 19 amino acids designed structures predicted using pepfold server binding designed peptide mentioned complex performed mutation approach used beatmusic server improve binding affinity designed peptide position amino acid substitutions leading increase binding affinity peptide mentioned complex determined finally resulting complexes simulated 40 ns using amber18 software results revealed 14 designed peptides wrywwkdwakqfrqfyrwf peptide exhibited highest affinity binding mentioned complex peptide can considered potential drug control multiple sclerosis disease patients carrying hlaa03 allelepmid34837787 doi101016 jjmgm2021108079,1.0
validation spanishlanguage version montreal cognitive assessment screening test cognitive impairment multiple sclerosis neurologia engl ed 2021 nov 23s21735808 21 001838 doi 101016 jnrleng201911007 online ahead printabstractbackground neuropsychological batteries traditionally used assessment cognitive impairment ci patients multiple sclerosis complex tests requiring long time administer simpler tests needed detect cognitive impairment daily clinical practiceobjective aimed evaluate diagnostic validity reliability montreal cognitive assessment moca test screening tool ci patients multiple sclerosis compared brief neuropsychological batterymaterial methods recruited 52 patients multiple sclerosis 615 women mean age standard deviation 417 115 years analysed reliability internal consistency interobserver reliability testretest reliability construct validity factor analysis pearson correlation coefficient coefficient determination criterion validity roc curve sensitivity specificity total agreement positive negative predictive values positive negative likelihood ratios fagan nomogram moca test populationresults prevalence ci 212 according findings brief neuropsychological battery 25 according moca test moca test showed good internal consistency cronbach alpha 0822 interobserver testretest reliability intraclass correlation coefficient 080 096 respectively correlation coefficient total brief neuropsychological battery moca test scores 082 optimal cutoff point roc curve 2526 yielding 91 sensitivity 93 specificityconclusion moca test valid reliable tool screening ci patients multiple sclerosispmid34836843 doi101016 jnrleng201911007,0.0
risk factors severe covid19 people multiple sclerosis systematic review metaanalysis rev neurol paris 2021 nov 4s00353787 21 007438 doi 101016 jneurol202110003 online ahead printabstractobjectives gather synthesize metaanalyze data regarding risk factors associated severe course covid19 among patients multiple sclerosis pwms methods medline embase scopus wos searched may 2021 briefly eligibility criteria included 1 studies assessing covid19 severity among adult pwms 2 definitive diagnoses high clinical suspicion covid19 3 categorization covid19 severity least two categories 4 quantitative effect size precision measurements 5 english language 6 clear effect size precision measures internal validity studies assessed using nih quality assessment tools list possible risk factors created based search results later used extraction synthesis metaanalysis dataresults thirteen studies included syntheses outcome measures either extracted papers obtained primary researchers calculated manually metaanalyses showed significantly p005 increased odds severe covid19 pwms assessed risk factors except smoking dmtsconclusion study facilitates evidencebased risk benefit assessments practice older men progressive ms anticd20 therapies risk unfortunate covid19 outcomepmid34836608 doi101016 jneurol202110003,0.0
walleyed bilateral internuclear ophthalmoplegia webino mean walleyed pract neurol 2021 nov 26practneurol2021003157 doi 101136 practneurol2021003157 online ahead printno abstractpmid34836932 doi101136 practneurol2021003157,0.0
comments quot initial clinical manifestation multiple sclerosis immunization pfizerbiontech covid19 vaccinequot j neuroimmunol j neuroimmunol 2021 nov 18 362577780 doi 101016 jjneuroim2021577780 online ahead printno abstractpmid34826735 doi101016 jjneuroim2021577780,0.0
anticd52 antibody treatment murine experimental autoimmune encephalomyelitis induces dynamic differential modulation innate immune cells peripheral immune central nervous systems immunology 2021 nov 26 doi 101111 imm13437 online ahead printabstractanticd52 antibody anticd52ab leads rapid depletion t b cells followed reconstitution immune cells tolerogenic characteristics however little known effect innate immune cells study experimental autoimmune encephalomyelitis eae mice administered murine anticd52ab investigate effect dendritic cells monocytes macrophages periphery lymphoid organs central nervous system cns data show blood splenic innate immune cells exhibited significantly increased expression mhcii costimulatory molecules associated increased capacity activating antigen specific t cells first day three weeks five daily treatment anticd52ab comparison controls contrast periphery microglia infiltrating macrophages cns exhibited reduced expression levels mhcii costimulatory molecules antibody treatment time points investigated compared controls furthermore transit response peripheral innate immune cells anticd52ab treatment also observed lymphocytedeficient scid mice suggesting changes direct consequence mass depletion lymphocytes periphery study demonstrates dynamic tissuespecific modulation innate immune cells phenotype function following antibody treatment findings differential modulation microglia infiltrating macrophages cns comparison innate immune cells peripheral organs support cns specific beneficial effect alemtuzumab treatment inhibiting neuroinflammation multiple sclerosis ms patientspmid34826154 doi101111 imm13437,0.0
economic societal burden multiple sclerosis lebanese society costofillness quality life study protocol expert rev pharmacoecon outcomes res 2021 nov 2618 doi 101080 1473716720222008242 online ahead printabstractthis protocol describes estimation societal costs qualityoflife qol burden multiple sclerosis ms lebanon crosssectional prevalencebased burdenofillness study carried premier ms center lebanon enrolled lebanese patients aged 18 years older diagnosed ms 6 months study uses bottomup approach estimate costofillness coi qol using retrospective facetoface interview questionnaire resource utilization questionnaire adapted lebanese context clinical health economics experts methodologies used estimate consumption healthcare resources informal care productivity losses welldefined aligned lebanese healthcare system costs presented overall ms severity levels qol measured using euroqol eq5d5 l multiple sclerosis international quality life musiqol instrument protocol pioneers informing design future coi qol studies low middleincome countries lmics methods used applied similar lmics furthermore provide recommendations discuss challenges conducting highquality burdenofillness study lmics steps taken meet using case lebanonpmid34826264 doi101080 1473716720222008242,0.0
effects mannuronic acid il1beta il17a stat1 stat3 gene expression tlr2 tlr4 molecules multiple sclerosis j clin pharmacol 2021 nov 25 doi 101002 jcph2008 online ahead printabstractmultiple sclerosis ms chronic neurologic disease defined inflammation demyelination central nervous system cns comes variable degrees axonal neuronal damage efficacy dmannuronic acid m2000 novel drug immunosuppressive properties patented pct ep2017 067920 shown experimental model ms study effects m2000 il1 il17a stat1 stat3 gene expression tlr2 tlr4 molecules secondary progressive ms spms patients evaluated study 14 spms patients 14 healthy subjects control group entered phase 2 clinical trial clinical trial identifier irct2016111313739n6 gene expression il1 il17a stat1 stat3 assessed baseline measured 6 months therapy m2000 using quantitative realtime pcr method moreover expression tlr2 tlr4 molecules peripheral blood mononuclear cell pbmcs evaluated flow cytometry method gene expression il17a stat1 stat3 ms patients decreased six months therapy m2000 comparing treatment also gene expression il1 decreased numerically six months furthermore expression tlr2 tlr4 pbmcs patients declined compared baseline results investigation revealed m2000 downregulate il17 stat1 stat3 genes spms patients also reduce expression tlr2 tlr4 pbmcs moreover m2000 declined numerically il gene expression article protected copyright rights reservedpmid34825387 doi101002 jcph2008,1.0
autoimmunity motion mechanisms immune regulation destruction revealed vivo imaging immunol rev 2021 nov 25 doi 101111 imr13043 online ahead printabstractautoimmunity arises mechanisms immune tolerance fail discuss mechanisms t cell activation tolerance dynamics autoimmune response site disease live imaging autoimmunity provides ability analyze immune cell dynamics singlecell level within complex intact environment disease occurs analyses revealed mechanisms t cell activation tolerance lymph nodes mechanisms t cell entry sites autoimmune disease mechanisms leading pathogenesis protection autoimmune lesions overarching conclusions point stable versus transient t cell antigen presenting cell interactions dictating balance t cell activation tolerance t cell restimulation driver pathogenesis site autoimmunity findings models multiple sclerosis type 1 diabetes highlighted however results implications basic mechanisms t cell regulation immune responses tumor immunity autoimmunitypmid34825390 doi101111 imr13043,0.0
old new plasma exchange used fill therapeutic gap neurology j neurol sci 2021 nov 11120056 doi 101016 jjns2021120056 online ahead printabstractthe global tally neurological disorders exponentially rising yet effective therapies remain evasive great deal research novel small molecules immunotherapies gene therapies fill therapeutic gap believe greater focus plasma exchange research clinical tool may provide useful insight pathological mechanisms effective treatment strategies plasma exchange traditionally used treat antibodymediated neurological diseases myasthenia gravis neuromyelitis optica much wider future potential uses neurology plasma exchange antibody specific also removes variety plasmasoluble factors including agerelated diseaseassociated neurotoxic proteins fibrinogen amyloid research develops role bloodbrain barrier immunological alterations diseases typically regarded immunedriven interest neurotoxic plasma proteins grows highlight plasma exchange may uses outside antibodymediated neurological diseases removing neurotoxic proteins systemic circulationpmid34823869 doi101016 jjns2021120056,0.0
ctla4 gene mutation multiple sclerosis case report literature review j microbiol immunol infect 2021 nov 13s16841182 21 00236x doi 101016 jjmii202110009 online ahead printabstractwe reported patient autoimmunity multiple sclerosis immunodeficiency hypogammaglobulinemia severe infections enteropathy diarrhea intestinal inflammation splenomegaly lymphadenopathy lymphocytic infiltration nonlymphoid organs lung gut brain patient found heterozygous mutation cytotoxic t lymphocyte antigen4 excellent response abataceptpmid34824019 doi101016 jjmii202110009,0.0
therapeutic effect peglated nanoliposome pistachio unsaturated oils efficacy attenuate inflammation multiple sclerosis randomized doubleblind placebocontrolled clinical trial phase j neuroimmunol 2021 nov 17 362577768 doi 101016 jjneuroim2021577768 online ahead printabstractthe aim study evaluate therapeutic effect peglated nanoliposome pistachio unsaturated oils pegnlpuos efficacy attenuate inflammation multiple sclerosis ms study randomized doubleblind placebocontrolled clinical trial phase level docosahexaenoic eicosapentaenoic acid significantly increased level matrix metallopeptidase9 significantly decreased ms patients treated pegnlpuos level cytokine showed th2biased response attenuation inflammation treatment pegnlpuos number relapses disability scores t2 lesions significantly decreased treatment pegnlpuospmid34823120 doi101016 jjneuroim2021577768,0.0
quantitative analysis spinal cord neuropathology experimental autoimmune encephalomyelitis j neuroimmunol 2021 nov 18 362577777 doi 101016 jjneuroim2021577777 online ahead printabstractmultiple sclerosis inflammatory neurodegenerative condition frequently modeled using experimental autoimmune encephalomyelitis eae current methods eae histology include imprecise qualitative assessments timeconsuming analyses selected regions increasing interest neuroprotective reparative therapies important potential therapeutics evaluated eae quantitative neuropathology describe quantitative whole slide imaging immunofluorescence method allows longitudinal sections entire eae thoracic spinal cord investigated extent neuroinflammation axonal loss myelin density method impact ms research making histological comparisons eae increasingly robustpmid34823122 doi101016 jjneuroim2021577777,1.0
distinct immunological features inflammatory demyelinating diseases central nervous system neuroimmunomodulation 2021 nov 25111 doi 101159 000519835 online ahead printabstractobjective immunological features neuromyelitis optica spectrum disorder nmosd multiple sclerosis ms myelin oligodendrocyte glycoprotein antibodyassociated disease mogad lacked systemic comparisons accordingly aimed investigate immunological differences nmosd ms mogadmethods patients mogad ms nmosd received immunological tests including cytokine profiles cytometry analysis lymphocyte subgroups retrospectively reviewed divided training validation sets discriminatory models based immunological data established identify optimal classifiers using orthogonal partial least square discriminant analysis oplsda constructed models tested another independent cohortresults oplsda immunological data 50 patients 26 nmosd 14 ms 10 mogad demonstrated discriminatory values relatively low level tlymphocyte subsets especially cd4+ t cells mogad decreased nk cell eosinophil lymphocyte level elevated neutrophiltolymphocyte ratio nmosd declined ifnproducing cd4+ t cells th increased il8 concentration ms models nmosd vs ms nmosd vs mogad ms vs mogad exhibited significant predictive value accuracy 85 conclusions nmosd ms mogad may different pathogenesis several immunological biomarkers can serve potential classifiers clinicallypmid34823248 doi101159 000519835,1.0
understanding quality life across different clinical subtypes multiple sclerosis thematic analysis qual life res 2021 nov 25 doi 101007 s11136021030417 online ahead printabstractpurpose multiple sclerosis ms neurological disease different clinical presentations illness trajectories aim study explore factors important quality life qol people ms pwms understand may differ across three subtypesmethods convenience purposive sampling employed semistructured interviews conducted people relapsingremitting ms n 16 secondary progressive ms n 14 primary progressive ms n 13 interviews audio recorded transcribed verbatim thematic analysis involving inductive deductive processes separate analysis subtype made inductive process examining similarities differences across three subtypes deductive processfindings four factors identified important influence qol pwms restricted disrupted enjoyment disturbed future challenged sense self wellbeing significant others themes reflect pwms commonly perceived enjoyment purpose life also illustrating qol may questioned new perspectives going forward ms challenges sense self increased concerns significant others result ms subtype differences attributed different illness trajectories relapsing progressiveconclusions subtype differences negative impact ms qol clinicians encouraged understand challenges different illness trajectories particular traumatic nature relapses steady worsening symptoms among progressive subtypes mspmid34822047 doi101007 s11136021030417,0.0
personalized prediction rehabilitation outcomes multiple sclerosis proofofconcept using clinical data digital health metrics machine learning med biol eng comput 2021 nov 25 doi 101007 s1151702102467y online ahead printabstractpredicting upper limb neurorehabilitation outcomes persons multiple sclerosis pwms essential optimize therapy allocation previous research identified populationlevel predictors linear models clinical data work explores feasibility predicting individual neurorehabilitation outcomes using machine learning clinical data digital health metrics machine learning models trained clinical data digital health metrics recorded preintervention 11 pwms dependent variables indicated whether pwms considerably improved across intervention defined action research arm test arat box block test bbt nine hole peg test nhpt improvements arat bbt accurately predicted 88 83 accuracy using patient master data improvements nhpt predicted moderate accuracy 73 required knowledge sensorimotor impairments assessing digital health metrics clinical scales increased accuracy 10 nonlinear models improved accuracy bbt + 9 arat 1 nhpt 2 work demonstrates feasibility predicting upper limb neurorehabilitation outcomes pwms justifies development representative prediction models future digital health metrics improved prediction changes hand control thereby underlining advanced sensitivity graphical abstract work explores feasibility predicting individual neurorehabilitation outcomes using machine learning clinical data digital health metricspmid34822120 doi101007 s1151702102467y,0.0
relapse activity chronic phase antimyelinoligodendrocyte glycoprotein antibodyassociated disease j neurol 2021 nov 25 doi 101007 s0041502110914x online ahead printabstractobjective patterns relapse relapseprevention strategies antimyelin oligodendrocyte glycoprotein antibodyassociated disease mogad completely investigated compared patterns relapse later stages mogad antiaquaporin4 antibody aqp4ab positive neuromyelitis optica spectrum disorder nmosd methods observational comparative cohort study 66 patients mogad 90 aqp4abpositive nmosd enrolled compared patterns relapse annualized relapse rates arrs first 10 years disease onset stratified relapseprevention treatmentsresults approximately 50 patients mogad experienced relapses first 10 years among undergoing relapseprevention treatments arrs first 5 years slightly lower mogad patients aqp4abpositive nmosd patients mogad vs aqp4ab nmosd 019 vs 030 p 00753 5 years arr decreased mogad patients mogad vs aqp4ab nmosd 005 vs 034 p 00001 72 reduction first 5 years p 00090 eight 615 13 mogad patients 10year followup disease onset showed relapse 10 years onset clustering timing phenotype attacks observed disease patients effectiveness longterm lowdose oral psl relapse prevention patients mogad determinedconclusions relapse risk patients mogad generally lower patients aqp4abpositive nmosd especially 5 years onset meanwhile relapses later 10 years onset rare diseasespmid34820735 doi101007 s0041502110914x,1.0
evidence disease activity neda concept ms impact spinal cord mri j neurol 2021 nov 24 doi 101007 s00415021109012 online ahead printabstractbackground measures define treatment response evidence disease activity neda routinely used multiple sclerosis ms clinical practice although spinal cord involvement frequent feature ms magnetic resonance imaging mri monitoring routinely performedobjective assess impact spinal cord mri definition neda cohort people ms pwms available spinal cord imaging performed routine monitoringmethods included 115 pwms undergoing treatment firstline diseasemodifying therapies dmts retrospectively analyzed presence neda whole cohort either considering spinal cord imagingresults considering clinical brain mri measures 97 115 pwms 843 satisfied criteria neda cohort number pwms neda significantly decreased 88 765 p 001 considering also spinal cord imagingconclusion findings suggest routine clinical practice spinal cord mri monitoring pwms firstline dmts leads slight significant change proportion subjects classified clinically radiologically stable according neda definitionpmid34820734 doi101007 s00415021109012,0.0
standardized mortality ratios multiple sclerosis systematic review metaanalysis acta neurol scand 2021 nov 24 doi 101111 ane13559 online ahead printabstractobjective perform metaanalysis allcause causespecific genderspecific standardized mortality ratio crude mortality rate people multiple sclerosis also examined temporal trends datamethods medline cochrane library scopus searched keywords multiple sclerosis standardized mortality ratio standardized mortality ratio included longitudinal studies available data number deaths followup period person years reports standardized mortality ratio smr crude mortality ratio cmr calculated smr extracted cmrs logsmr pooled method inverse variance metaregression models used investigate temporal trendsresults fiftyseven articles screened fifteen studies included covering period 19492013 160 000 patients 21 225 deaths allcause smr people ms 261 95 ci 258 265 men 247 95 ci 242 252 women 257 95 ci 253 261 cmr 1345 1000 person years causespecific smr 174 167 181 cvd 470 445 487 respiratory disease infection 181 164 20 accident suicide 099 093 106 cancer metaregression analysis smr compared midpoint followup year revealed relationship coefficient 0001 p 98 conclusions people multiple sclerosis ms reduced overall survival increased risk death cardiovascular respiratory infectious disease well accidents suicide appear changed last 65 yearspmid34820847 doi101111 ane13559,0.0
timing treatment endogenous opioid alters immune response spinal cord pathology female mice experimental autoimmune encephalomyelitis j neurosci res 2021 nov 25 doi 101002 jnr24983 online ahead printabstractmultiple sclerosis ms progressive disease central nervous system cns primarily affects women second third decade life mechanism hypothesized involve unregulated peripheral inflammation resulting bloodbrain barrier damage eventual axonal damage demyelination based understanding animal model ms experimental autoimmune encephalomyelitis eae often utilized study lymphocyte activation therapeutic paradigms exogenous opioid growth factor ogf lowdose naltrexone ldn treatment can modulate eae little reported regarding ogf ldn effects peripheral inflammation microglia activation macrophage proliferation moreover little known differential responses ldn ogf relative duration timing treatment utilizing female mouse model eae two treatment regimens established investigate differences prophylactic treatment traditional therapy initiated time disease presentation prophylactic ogf ldn treatment delayed onset behavior suppressed neutrophil replication curtailed lymphocyte proliferation ultimately improved behavioral outcome traditional therapy ogf ldn reversed behavioral deficits restored ogf il17 serum levels inhibited microglial activation within 8 days reduced serum ogf levels untreated eae mice correlated increased microglia activation within lumbar spinal cords treatment regimens ogf ldn reduced activated microglia whereas prophylactic treatment prevented cns macrophage aggregation data demonstrate timing ldn ogf treatment initiation alters outcomes can prevent reverse behavioral deficits cytokine activation spinal cord pathologypmid34821408 doi101002 jnr24983,1.0
antiinflammatory activity natural herbalmarine drug ms14 sant susp compared sodium salicylate methylprednisolone rat model multiple sclerosis eur j transl myol 2021 nov 24 doi 104081 ejtm202210169 online ahead printabstracta natural compound marine herbal origin used persian traditional medicine relieve symptoms multiple sclerosis present study investigated antiinflammatory effects patented extracts traditional receipt ms14 preliminary experiment used seven groups six rats control group received vehicle two positive control groups treated either sodium salicylate 300 mg kg intraperitoneal ip methyl prednisolon mpn 10 mg kg ip test groups treated solution centrifuged ms14 sant 100 mg kg suspension ms14 susp 100 150 300 mg kg ip thirty minutes paw volume measured plethysmometer immediately formalin solution injected subcutaneously hind paw hour inflamed paw volume measured days 28 inflamed paw volume measured immediately drugs injected ip antiinflammatory effect mpn significant days 5 6 antiinflammatory effect ss significant 6th day antiinflammatory effect sant ms14 100 mg kg also significant 6th day susp ms14 150 mg kg significantly reduced edema second 6th day intraperitoneal injection susp ms14 300 mg kg toxic excluded study research indicates ms14 possesses antiinflammatory effect intraperitoneal administration comparative antiinflammatory effects ms14 glucocorticoids study may justify possible mechanism action multiple sclerosis studies will provid strong statistically confirmatory effects animals safety human trialspmid34818879 doi104081 ejtm202210169,1.0
prevalence multiple sclerosis liguria region italy estimate using capturerecapture method neurol sci 2021 nov 24 doi 101007 s1007202105718w online ahead printno abstractpmid34817728 doi101007 s1007202105718w,0.0
correction parkinson#39 s disease covid19 systematic review metaanalysis neurol sci 2021 nov 24 doi 101007 s10072021057813 online ahead printno abstractpmid34817731 doi101007 s10072021057813,0.0
slowing loss physical function amyotrophic lateral sclerosis edaravone post hoc analysis alsfrsr item scores pivotal study mci18619 muscle nerve 2021 nov 23 doi 101002 mus27467 online ahead printabstractintroduction phase 3 study mci18619 demonstrated less loss physical function edaravone versus placebo measured revised amyotrophic lateral sclerosis functional rating scale alsfrsr total score 1point drop individual alsfrsr item may clinically meaningful assessed alsfrsr item score changes identify clinical features protected edaravone treatmentmethods timetoevent analysis used assess cumulative probabilities reductions alsfrsr item scores amyotrophic lateral sclerosis assessment questionnaire alsaq40 subdomain scoresresults edaravone use accompanied 1 delayed drop 1 point alsfrsr item score 4 items salivation walking climbing stairs orthopnea unadjusted 2 items walking climbing stairs bonferroni correction multiple comparisons 2 delayed score transition 4 3 baseline 2 5 items swallowing eating motion walking climbing stairs orthopnea unadjusted 1 item climbing stairs bonferroni correction multiple comparisons 3 delayed worsening alsaq40 domain scores representing daily living independence eating drinking unadjusted discussion posthoc analyses identified alsfrsr item scores alsaq40 domain scores associated preserved gross motor function healthrelated quality life respectively edaravone treatment limitations posthoc analyses considered interpreting results recommend clinical trials employing alsfrsr include type analysis prespecified secondary outcome measurepmid34816454 doi101002 mus27467,0.0
pain quality life religiosity people multiple sclerosis neurol sci 2021 nov 23 doi 101007 s10072021057591 online ahead printabstractpurpose investigate multiple sclerosis ms patients relationship pain religiosity determine whether distinct dimensions religiosity associated quality lifemethods ms patients clinical followup filled visual analogue scale pain vas mc gill questionnaire mcgq 36item short form health survey sf36 religious attitude scale ras expanded disability status scale edss assessedresults ninetytwo ms patients enrolled two declined negative correlation religious practice faith domains sf36 positive correlation sensory affective evaluative aspects pain mcgq religious practices evaluative aspects pain mcgq faith edss significantly higher practitioner believers compared practitionersconclusions disabled ms patients worse quality life also due physical pain find source comfort faith religious practices pain relieved prayer therefore may guess ms poor beneficial effect religiosity practice pain perception may linked structural functional damage neural circuits involved reducing pain prayerpmid34816315 doi101007 s10072021057591,0.0
health effects vitamin d supplementation evidence human studies nat rev endocrinol 2021 nov 23 doi 101038 s4157402100593z online ahead printabstractvitamin d supplementation can prevent cure nutritional rickets infants children preclinical observational data suggest vitamin d endocrine system wide spectrum skeletal extraskeletal activities consensus severe vitamin d deficiency serum 25hydroxyvitamin d 25ohd concentration 30 nmol l corrected whereas guidelines recommend serum 25ohd concentrations 50 nmol l optimal bone health older adults however causal link vitamin d many extraskeletal outcomes remains unclear vital vida d2d randomized clinical trials combined number participants 30 000 indicated vitamin d supplementation vitamin dreplete adults baseline serum 25ohd 50 nmol l prevent cancer cardiovascular events falls progression type 2 diabetes mellitus post hoc analysis suggested extraskeletal benefits individuals vitamin d deficiency 60 mendelian randomization studies designed minimize bias confounding evaluated consequences lifelong genetically lowered serum 25ohd concentrations various outcomes studies found null effects four mendelian randomization studies found increased risk multiple sclerosis individuals genetically lowered serum 25ohd concentrations conclusion supplementation vitamin dreplete individuals provide demonstrable health benefits conclusion contradict older guidelines severe vitamin d deficiency prevented correctedpmid34815552 doi101038 s4157402100593z,0.0
clinical pathological features renal epithelioid angiomyolipoma pecoma single institution series urol oncol 2021 nov 20s10781439 21 00435x doi 101016 jurolonc202109010 online ahead printabstractrenal angiomyolipomas benign tumors kidney belong pecoma perivascular epithelioid cell family epithelioid amls eaml rare monotypic subtype malignant potential can occur sporadically associated tuberous sclerosis tsc due epithelioid nature eamls can closely resemble highgrade renal cell carcinoma rcc may result misdiagnosis multiple clinicopathologic parameters predictive worse outcomes patients eaml can used stratify patients groups low intermediate high risk disease progression high index suspicion thorough immunohistochemical study required correctly diagnose eaml radiographically eamls also diagnostic challenge share features rcc ct mr imaging due close mimicry true incidence eaml thought much higher 200 cases reported literature report series four patients diagnosed eaml compare clinical courses also report successful treatment patient pulmonary metastasis eaml using mtor inhibitor everolimus identifying eaml recognizing highrisk features possible mtor inhibitors may meaningful role adjuvant treatment patientspmid34815169 doi101016 jurolonc202109010,0.0
oral dmannose treatment suppresses experimental autoimmune encephalomyelitis via induction regulatory t cells j neuroimmunol 2021 nov 18 362577778 doi 101016 jjneuroim2021577778 online ahead printabstractdmannose dm glucose epimer found natural products especially fruits mouse models diabetes airway inflammation dm supplementation via drinking water attenuated pathology modifying cellular energy metabolism leading activation latent transforming growth factor beta tgf turn induced t regulatory cells tregs given tregs important controlling neuroinflammation experimental autoimmune encephalomyelitis eae likely multiple sclerosis ms hypothesized dm also suppress eae found dm delayed disease onset reduced disease severity two models eae importantly dm treatment prevented relapses relapsingremitting model eae mimics common clinical manifestation ms eae suppression accompanied increased frequency cd4+foxp3+ tregs central nervous system suggesting eae suppression resulted treg cell induction dm findings suggest dm potential safe lowcost complementary therapy mspmid34814011 doi101016 jjneuroim2021577778,0.0
greater mastery associated lower depression risk large international cohort people multiple sclerosis 25 years qual life res 2021 nov 23 doi 101007 s11136021030337 online ahead printabstractbackground mastery extent individual perceives life circumstances control predominantly influenced external factors relationship mastery clinical outcomes people multiple sclerosis pwms wellresearched assessed relationships mastery fatigue disability relapse number depression risk among pwms 25 years followupmethods data health outcomes lifestyle sample people multiple sclerosis study among 839 participants completed 25 5year reviews analysed mastery measured pearlin mastery scale fatigue fatigue severity scale depression risk patient health questionnaire9 disability patientdetermined disease steps diagnosed relapse number previous 12 months queried crosssectional prospective analyses undertaken logbinomial logmultinomial poisson regression appropriate adjusted relevant confoundersresults crosssectionally pwms highest quartile mastery 25 28 90 lower frequency depression risk 60 lower frequency clinically significant fatigue 77 fewer severe disability largely robust adjustment prospectively top two quartiles mastery 2125 25 28 66 74 lower subsequent depression risk robust adjustment significant associations seen prospectively change fatigue disability relapse number however robust associations mastery relapse number evidentconclusions prospectively protective relationship mastery subsequent risk depression observed suggesting may point intervention improve wellbeing pwmspmid34813035 doi101007 s11136021030337,0.0
group paks myelin formation repair central nervous system biol rev camb philos soc 2021 nov 22 doi 101111 brv12815 online ahead printabstractp21activated kinases paks family cell division control protein 42 rasrelated c3 botulinum toxin substrate 1 cdc42 rac1 activated serine threonine kinases group paks pak13 distinct activation mechanisms group ii paks pak46 focus review transformed cancer cells paks regulate variety cellular processes molecular pathways also important myelin formation repair central nervous system cns de novo mutations group paks frequently seen children neurodevelopmental defects white matter anomalies group paks regulate virtually every aspect neuronal development function yet functions cns myelination remyelination remain incompletely defined herein highlight current understanding paks regulating cellular molecular pathways discuss status pakregulated pathways oligodendrocyte development point outstanding questions future directions research field group paks oligodendrocyte developmentpmid34811887 doi101111 brv12815,1.0
covid vaccination patients treatment rituximab presentation two cases iran review current knowledge specific focus pemphigus dermatol ther 2021 nov 23e15216 doi 101111 dth15216 online ahead printabstractbackground sarscov2 vaccines approved without longterm monitoring due emergent situations raised issues timing protocol receiving vaccines specific situations patients receiving immunomodulatory agents including rituximab widely used various disorders multiple sclerosis pemphigus many rheumatologic disorderscase presentation described two cases pemphigus vulgaris new case one flareup following vaccination astrazeneca iran reviewed existing data regard searching pubmed google scholar scopus relevant papers published june 28 2021 access fulltexts includedresults found recommendations made rheumatologists neurologists dermatologists regard vaccination timing group patients tried summarize provide practical guide cliniciansconclusion clinicians perform careful individualized riskbenefit assessment patients consider delay rtx administration completion covid vaccination considerable risk disease relapse organ failure moreover choosing vaccines potential providing protection single dose especially countries limited access vaccines may reasonable approach article protected copyright rights reservedpmid34811862 doi101111 dth15216,0.0
effect interferonbeta therapy thelper 17#x2f mir326 thelper 1#x2f mir29b3p axis relapsingremitting multiple sclerosis patients neuroimmunomodulation 2021 nov 2219 doi 101159 000519777 online ahead printabstractbackground aimed evaluate therapeutic effects interferonbeta ifn hsamir29b3p hsamir326 isolated thelper th 1 th17 cells expressed relapsingremitting multiple sclerosis rrms patients 1 year treatment ifnmethods study done 19 rrms patients pre posttreatment ifn evaluate frequency th1 th17 cells flow cytometry expression level hsamir29b3p hsamir326 isolated th1 th17 cells assessed quantitative polymerase chain reaction enzymelinked immunosorbent assay also used measure plasma levels interferon gamma interleukin il 17aresults th17 cells plasma levels il17a decreased rrms patients ifn therapy hsamir29b3p hsamir326 expression significant change treated rrms patients versus baseline mxa gene expression significantly induced upon ifn therapy patients rrmsconclusion ifn therapy effective th17 th1 reform altered expression hsamir326 hsamir29b3p th17 th1 respectivelypmid34808619 doi101159 000519777,0.0
mouse homologue human hlado preempt autoimmunity controls murine gammaherpesvirus mhv68 j immunol 2021 nov 22ji2100650 doi 104049 jimmunol2100650 online ahead printabstracth2o human hlado relatively conserved nonclassical mhc class ii mhcii like molecule h2o interaction human hladm edits repertoire peptides presented tcrs mhcii long hypothesized human hladm inhibition h2o provides protection autoimmunity preventing binding highaffinity selfpeptides mhcii available evidence supporting hypothesis however inconclusive possibility still remained effect h2o deficiency autoimmunity better revealed using h2odeficient mice already genetically predisposed autoimmunity study generated used autoimmunityprone mouse models systemic lupus erythematosus organspecific autoimmunity type 1 diabetes multiple sclerosis definitively test whether h2o prevents autoimmune pathology whereas data failed support significance h2o protection autoimmunity found critical controlling herpesvirus mhv68 thus propose h2o editing mhcii peptide repertoire may evolved safeguard specific highly prevalent viral pathogenspmid34810225 doi104049 jimmunol2100650,0.0
evaluating contribution reactive balance prediction fall rates crosssectionally longitudinally persons multiple sclerosis gait posture 2021 nov 15 923035 doi 101016 jgaitpost202111008 online ahead printabstractbackground falls common persons multiple sclerosis pwms reactive postural controlones response balance perturbationis likely aspect fall risk however relationship reactive posture falls poorly understood pwmsobjective evaluated tibialis anterior muscle onset latency ta latency balance perturbations predictor fall rates pwms controlling clinical functional sensory psychological cognitive factorsmethod baseline 18month cohort study 122 participants ms edss 223 included assessments conducted every 6 monthsresults original 122 participants baseline collection data available 41 39 34 people 6 12 18 month followups respectively percent fallers four time points 353 122 154 205 crosssectionally ie baseline timed upandgo falls efficacy scale international fesi ta latency perturbations significant predictors retrospective falls rates using negative binomial regression longitudinally randomeffects negative binomial regression found traitlevel fesi stroop colorword ta latency significant predictors falls ratesconclusion delays automatic postural responses seem account uniquely fall rates pwmsbeyond clinical balance mobility measures delays may contribute increased fall rate pwms addition brief selfreport instruments fesi cognitive assessments muscle onset balance perturbations may valuable tool predicting falls mspmid34808516 doi101016 jgaitpost202111008,0.0
absence erap1 b cells increases susceptibility central nervous system autoimmunity alters b cell biology mechanistically explains genetic associations erap1 multiple sclerosis j immunol 2021 nov 22ji2100813 doi 104049 jimmunol2100813 online ahead printabstracthundreds genes linked multiple sclerosis ms yet underlying mechanisms behind associations investigated fraction cases endoplasmic reticulum aminopeptidase 1 erap1 endoplasmic reticulumlocalized aminopeptidase important roles trimming peptides destined mhc class regulation innate immune responses genetic polymorphisms erap1 linked multiple autoimmune diseases study present knowledge first mechanistic studies performed uncover polymorphisms erap1 associated increased susceptibility ms combining multiple mouse models cns autoimmunity highdimensional singlecell spectral cytometry adoptive transfer studies integrative analysis human singlecell rnasequencing datasets identify intrinsic defect b cells primarily responsible mice lacking erap1 susceptible cns autoimmunity adoptive transfer b cells lacking erap1 b celldeficient mice recapitulates susceptibility found b cells lacking erap1 display decreased proliferation vivo express higher levels activation costimulatory markers integrative analysis singlecell rna sequencing b cells 36 individuals revealed subsetconserved differences gene expression pathway activation individuals harboring mslinked k528r erap1 singlenucleotide polymorphism finally studies also led us create knowledge first murine proteinlevel map cns il10+ immune compartment steady state neuroinflammation studies identify role erap1 modulation b cells highlight one reason polymorphisms gene linked mspmid34810226 doi104049 jimmunol2100813,0.0
humoral tcellspecific immune responses sarscov2 mrna vaccination patients ms using different diseasemodifying therapies neurology 2021 nov 22101212 wnl0000000000013108 doi 101212 wnl0000000000013108 online ahead printabstractobjective evaluate immunespecific response full sarscov2 vaccination multiple sclerosis ms patients treated different disease modifying drugs detection serological tcell responsesmethods health care workers hcws ms patients completed twodose schedule mrnabased vaccine sarscov2 last 24 weeks enrolled two parallel prospective studies conducted rome italy national institute infectious diseases spallanzaniircss san camillo forlanini hospital serological response evaluated quantifying regionbindingdomain rbd neutralizingantibodies cellmediated response analyzed wholeblood test quantifying interferon ifn response spike peptides cells responding spike stimulation identified facs analysisresults prospectively enrolled 186 vaccinated individuals 78 hcws 108 ms patients twentyeight ms patients treated ifn 35 fingolimod 20 cladribine 25 ocrelizumab lower antirbdantibody response rate found patients treated ocrelizumab 40 p00001 fingolimod 857 p00023 compared hcws patients treated cladribine ifn antirbdantibody median titer lower patients treated ocrelizumab p00001 fingolimod p00001 cladribine p0010 compared hcws ifntreated patients importantly serum neutralizing activity present hcws tested minority fingolimodtreated patients 166 tcellspecific response detected majority ms patients 62 albeit significantly lower ifn levels compared hcws lowest frequency tcell response found fingolimodtreated patients 143 tcellspecific response correlated lymphocyte count antirbd antibody titer rho0554 p00001 rho0255 p00078 respectively finally ifn tcell response mediated cd4+ cd8+ t cellsconclusion mrna vaccines induce humoral cellmediated specific immune responses spike peptides hcws majority ms patients results carry relevant implications managing vaccinations suggesting promote vaccination treated ms patientsclassification evidence study provides class iii data covid mrna vaccination induces humoral cellmediated specific immune responses viral spike proteins majority ms patientspmid34810244 doi101212 wnl0000000000013108,0.0
cave paintings shallow watersthe case advancing spinal cord imaging multiple sclerosis jama neurol 2021 nov 22 doi 101001 jamaneurol20214245 online ahead printno abstractpmid34807242 doi101001 jamaneurol20214245,0.0
selfreported behaviour change among multiple sclerosis community members interested laypeople following participation free online course multiple sclerosis health promot j austr 2021 nov 22 doi 101002 hpja559 online ahead printabstractissue addressed evaluated impact understanding multiple sclerosis ms massive open online course intended increase understanding awareness ms selfreported health behaviour changemethods observational cohort study evaluating pre baseline postcourse 810week followup survey data main study outcomes selfreported health behaviour change change type measurable improvement also collected participant characteristic data eg age physical activity compared participants reported health behaviour change followup compared improved using chi square ttests participant characteristics change types change improvement described descriptivelyresults n560 course completers included study study cohort included ms community members eg people ms healthcare providers nonmembers n247 441 reported behaviour change 1 area followup 160 648 reported measurable change 109 681 showed improvement participants reported change improved significantly lower precourse health behaviours characteristics eg quality life diet quality reported change types knowledge exercise physical activity diet care practiceconclusion understanding ms encourages health behaviour change among course completers primarily provision information goalsetting activities discussions online education intervention can effectively encourage health behaviour change 810week followup period information provision including scientific evidence lived experience goalsetting activities discussions primary mechanisms underpinning changepmid34807490 doi101002 hpja559,0.0
functional connectivity lateralisation shift resting state networks linked visuospatial memory white matter microstructure relapsingremitting multiple sclerosis brain topogr 2021 nov 22 doi 101007 s1054802100881x online ahead printabstractlaterality patterns resting state networks rsn change various neuropsychiatric conditions multiple sclerosis ms causes neurocognitive symptoms involving dysfunctional largescale brain networks yet whether healthy laterality patterns rsns maintained ms whether altered laterality patterns explain disease symptoms explicitly investigated analysed functional mri diffusion tensor imaging data 24 relapsingremitting ms patients 25 healthy participants performed grouplevel independent component analysis used dual regression estimate individual versions wellestablished rsns voxelwise laterality indices calculated rsn group differences assessed via general linear modelbased approach relationship functional laterality white matter microstructural asymmetry assessed using tractbased spatial statistics spearmans correlation calculated laterality indices brief international cognitive assessment multiple sclerosis scores functional laterality dorsal attention network showed significant leftward shift ms group posterior intraparietal sulcus p 0033 defaultmode network laterality showed significant leftward shift ms group angular gyrus p 0005 diminished dorsal attention network laterality associated increased fractional anisotropy asymmetry superior longitudinal fasciculus p 002 defaultmode network leftward laterality angular gyrus associated higher bvmtr scores r 052 p 0023 results confirm previous descriptions rsn dysfunction relapsingremitting ms show altered functional connectivity lateralisation patterns rsns might contibute cognitive performance structural remodellation even patients mild clinical symptomspmid34807323 doi101007 s1054802100881x,0.0
theory mind emotion recognition emotional reactivity factors early multiple sclerosis results south american cohort appl neuropsychol adult 2021 nov 22111 doi 101080 2327909520212004542 online ahead printabstractobjectives study different components social cognition quality life patients early multiple sclerosis low expanded disability status scale test influence cognitive performance fatigue neuropsychiatric symptoms social cognition performancemethods thirtyfour patients relapsingremitting ms 2 years disease duration scores 2 edss 30 healthy controls underwent neuropsychological assessment brief repeatable neuropsychological test battery components social cognition emotion recognition theory mind empathy emotional reactivity assessed reading mind eyes test faux pas task international affective imagery system empathy quotient anxiety depression fatigue quality life measuredresults patients showed significant differences verbal memory executive functions social cognition especially emotion recognition tom regarding emotional reactivity patients showed positive bias interpretation valence neutral imagesconclusions patients early ms showed impairments several components social cognition independent cognitive performance neuropsychiatric symptoms fatigue social cognition deficits may present ms even early stagespmid34807785 doi101080 2327909520212004542,0.0
ager gene variant risk factor juvenile idiopathic arthritis j gene med 2021 nov 21e3399 doi 101002 jgm3399 online ahead printabstractbackground ager gene encodes cell surface multiligand receptor advanced glycation endproducts also capable binding molecules involved numerous pathways related inflammation apoptosis immunity study aimed investigate whether ager rs1035798 ga intronic polymorphism showing association multiple sclerosis rheumatoid arthritis adults related juvenile idiopathic arthritis jia methods caucasian children belarusian population enrolled study total 201 cases jia 37 juvenile systemic lupus erythematosus 222 children articular syndrome nonautoimmune etiology positive control jia 365 negative controls children without autoimmune inflammatory diseases genomic dna samples patients controls genotyped realtime pcr instrumentsresults marked association homozygous aa rs1035798 genotype jia p5104 found allele also associated jia p00058 well articular syndrome nonautoimmune etiology p00264 highest frequencies aa genotype found subgroups jia patients polyarthritis severe oligoarthritis aa genotype patients also smallest mean age jia onsetconclusions results demonstrate ager rs1035798 aa genotype risk factor jia belarusian children also suggest link ager aa genotype risk jia early onset severity however functional relevance rs1035798 polymorphism still unclearpmid34806241 doi101002 jgm3399,0.0
pediatric cervical kyphosis mri era 19842008 longterm follow literature review childs nerv syst 2021 nov 22 doi 101007 s0038102105409z online ahead printabstractobjective cervical kyphosis rare pediatric population may syndromic acquired secondary laminectomy neoplasia trauma regardless avoided prevent progressive spinal deformity neurological deficit longterm followup needed evaluate fusion status spine growth potential instability neurological functionmethods materials retrospective review 27 children 6 months 16 years cervical kyphotic deformity performed limited mri era 2008 provide longterm followup complex instrumentation available 27 patients 19 syndromic average age 536 years 8 nonsyndromic average age 14 years syndromes encountered spondyloepiphyseal dysplasia sed 4 spondylometaphyseal dysplasia 1 unnamed collagen abnormality syndrome 1 osteogenesis imperfecta oi 2 aarskog syndrome 1 weaver syndrome 1 larsen syndrome 1 multiple cervical level disconnection syndrome 1 klippelfeil 3 congenital absence c2 pars 4 nonsyndromic cases 2 neurofibromatosis nf1 prevertebral tumors fibromatosis 1 spontaneous kyphosis 1 postlaminectomy 4 factors considered age pathology flexibility cervical spine dynamic films reduction traction spinal cord compression patients flexible kyphosis underwent dorsal fixation children nonflexible ventral compression kyphosis crown halo traction irreducible kyphosis ventral decompression fusion well dorsal fusion eleven 19 syndromic children flexible reducible kyphosis underwent dorsal fixation alone four 8 nonsyndromic 2 nf1 needed ventral dorsal approachesresults preoperative deformity global local cobb angles well neurological status improved growth followup impaired encounter instability junctional kyphosis complications seen syndromic patients one patient sed showed delayed cantilever bending ventral fusion mass requiring reoperation 1 oi child left c5 c6 nerve root weakness anterior c4 c5 decompression resolved 1 year one child sed developed cervicothoracic junction scoliosis 18 years later thoracic scoliosis surgeryconclusions syndromic pathology presented early neurological dysfunction 24 rigid kyphosis attempt traction reduction successful tables 1 2 majority exhibited longterm improvement kyphosis function treatment algorithm literature review presented table 1 motor function modified japanese orthopedic association joa score children 24 37 score upper extremity unable move hands feed oneself 0 can move hands unable eat spoon 1 able eat spoon difficulty 2 able use spoon clumsy buttoning 3 healthy dysfunction 4 lower extremity unable sit stand 0 unable walk without cane walker 1 walks independently level floor needs support stairs 2 capable walking clumsy 3 dysfunction 4 table 2 pediatric cervical kyphosispreoperative evaluations case id year presented age sex diagnosis presentation imaging apex cobb angle degree reducibility preop traction syndromic #1 2003 4 years m sed progressive quadriparesis bladder incontinence severe c24 kyphosis cord compression c34 85 #2 2001 3 years m sed progressive quadriparesis c23 kyphosis dorsal c2 buckled cord c23 25 recurrent weakness recovery 2 years later kyphosis fusion site c23 33 #3 1997 13 years m sed neck pain hand weakness thoracic scoliosis c13 kyphosis os odontoideum c23 30 yes #4 2006 6 years f sed tingling hands bladder incontinence deformed c2 body odontoid c12 instability c23 27 yes #5 1997 4 years m smd quadriparesis previous c23 kyphosis oc3 dorsal fusion elsewhere fixed c12 dislocation c23 kyphosis oc4 fusion c2 35 partial yes 4 days #6 2007 13 years f syndromic collagen abnormality neck pain leg length discrepancies tl scoliosis quadriparesis bilateral c2 partial c3 spondylolysis ct levoscoliosis c23 35 partial yes 4 days #7 2003 14 years f osteogenesis imperfecta oi able use right upper extremity c35 kyphosis canal diameter 4 mm c4 c4 25 #8 1989 3 years f oi brucks syndrome quadriparesis age 9 months c1c3 posterior decompression fusion elsewhere progressive kyphosis worse weakness bend fusion c12 40 #9 1996 11 years m aarskog syndrome neck pain limited neck motion cervical myelopathy psychomotor delay c45 spondylolysis c56 kyphosis c5 30 yes 3 days #10 1989 3 years f weaver syndrome quadriparesis age 2 years elsewhere c1c3 dorsal rib fusion wires fusion failure c23 subluxation cord compression c23 3 yes yes 1 day #11 1986 11 years f larsen syndrome neck pain extension quadriparesis c23 kyphosis deformed bodies c25 os odontoideum c12 instability c23 28 yes yes 1 day #12 1996 5 years m multilevel cervical disconnect syndrome horner pupil right small right arm quadriparesis c4 c5 vertebral bodies behind c5 c5 body canal left vertebral artery c5 body c45 35 #13 1985 3 years f klippelfeil neck pain weak hands atlas assimilation c34 kyphosis posterior bony arches c3 c4 c34 40 yes #14 1994 3 years f klippelfeil unable sit floppy quadriparesis c23 kyphosis posterior arches c23 l4 c23 45 yes #15 1993 11 months f tuberous sclerosis spondylolysis c2 salam seizures quadriparesis pars c2 c23 kyphosis c23 30 yes #16 1998 2 years m c2 spondylolysis quadriparesis arms worse legs c2 spondylolysis c23 kyphosis c23 35 yes #17 1998 6 months m c2 spondylolysis failure thrive apneic spells weak arms endoscopy c23 kyphosis c2 lamina cord compression c34 mri c23 45 yes #18 1990 4 years f c2 spondylolysis developmental delay quadriparesis c2 spondylolysis c23 kyphosis c3 45 yes #19 1994 4 years f klippelfeil posterior c2 torticollis age 6 mo quadriparesis c23 kyphosis posterior arch c2 fused c34 bodies c23 45 yes nonsyndromic #20 1996 15 years m nf1 ventral prevertebral plexiform neurofibroma neck pain weak arms cervical myelopathy c45 kyphosis cord draped c45 enhanced prevertebral tumor c45 60 partial yes 4 days #21 1996 6 years m nf1 age 6 mo c13 laminectomies elsewhere progressive kyphosis quadriparesis c35 plexiform neurofibromas c24 kyphosis c34 45 #22 1993 11 years m fibromatosis neck pain gag right hemiparesis c2 body odontoid curved dorsally c23 kyphosis c2 40 yes 3 days #23 2007 13 f midcervical kyphosis neck pain unable move neck c34 kyphosis c34 45 yes halo vest elsewhere 6 weeks repeat traction referral #24 1998 12 years m chiari syringohydromyelia difficulty swallowing quadriparesis previous posterior fossa c13 decompression basilar invagination c34 kyphosis c34 50 yes halo traction 3 days #25 1994 16 years m chiari shm difficult speech quadriparesis previous posterior fossa c14 laminectomies c34 kyphosis basilar invagination c34 55 yes halo traction 3 days #26 2002 11 years m chordoma c35 initial quadriparesis improved posterior decompression worse dorsal lateral tumor c34 c34 20 yes traction 3 days #27 2006 13 years m c4 lamina aneurysmal bone cyst neck shoulder pain c4 laminectomy tumor resection worse 4 months later c45 kyphosis c34 40 yes table 3 pediatric cervical kyphosispostoperative evaluations case id diagnosis treatmentoperation complication po orthosis f u time fusion status preop cobb postop cobb preop joa postop joa comments syndromic #1 sed crown halo traction 1 median mandibular glossotomy resection c23 bodies rib graft fusion 2 dorsal oc3 rib graft fusion none halo vest 3 months soft collar 3 months 8 years complete anterior posterior fusion 85 10 2 8 complete neurological recovery #2 sed crown halo traction 1 median mandibular glossotomy c24 corpectomies c25 anterior rib graft fusion recurrent weakness 2 years s later halo vest 3 months 2 years fused 25 20 4 5 t scoliosis cardiac abnormalities walking quadriparesis redo ventral resection c14 iliac bone graft worsening quadriparesis minerva brace 1 year 18 years fused 33 15 3 5 much improved 6 months #3 sed crown halo traction dorsal oc4 fusion loop rib graft none miami j collar 3 months 10 years fused 30 13 4 7 works bookstore #4 sed crown halo traction dorsal oc3 fusion loop rib graft 4 years later developed ct scoliosis t scoliosis surgery miami j collar 3 months 14 years fused 27 5 5 7 ct scoliosis developed thoracic scoliosis correction #5 smd crown halo traction transoral c2 odontoid resection none minerva brace 6 months 20 years preop status 35 10 1 4 wheelchair works programmer #6 collagen abnormality crown halo traction c25 acdf c25 plate c34 lag screws junctional kyphosis 7 years later scoliosis correction miami j collar 6 weeks 12 years fused 36 5 4 7 abnormal vertebral arteries thoracic outlet syndrome maythurner syndrome #7 oi crown halo traction c35 corpectomies c26 orion plate iliac crest graft none soft collar 4 years fused 25 30 1 5 restrictive lung disease multiple fractures expired #8 oi bruck syndrome 1 redo c12 dorsal rib graft fusion change molded minerva brace 4 years fused 40 35 3 4 increased weakness age 7 2 11 years age anterior c37 decompression plate c37 worsening left deltoid biceps function molded minerva brace 30 years fused 52 34 3 5 lives alone wheelchair computer technologist uses hands well #9 aarskog syndrome crown halo traction c26 anterior cervical fusion iliac crest graft none molded minerva brace 20 years fused 30 14 4 7 works farm myelopathy syndrome family #10 weaver syndrome crown halo traction redo c14 dorsal rib graft fusion none miami j collar 2 years fused 3 10 2 5 neuroblastoma age 3 months chemotherapy stable #11 larsen syndrome crown halo traction oc5 dorsal fusion none halo vest 6 weeks miami j 3 months 6 years fused 28 10 3 7 well #12 multilevel cervical disconnect syndrome crown halo traction c5 corpectomy c46 iliac bone fusion anteriorly dorsal c46 fusion none halo vest 3 months 5 years fused 35 5 3 7 persistent horner pupil #13 klippelfeil crown halo traction c26 posterior rib graft fusion none halo vest 3 months 19 years fused 40 12 3 7 hearing loss genitourinary abnormalities sprengels deformity #14 klippelfeil crown halo c25 dorsal rib graft fusion none halo vest 3 months 35 years fused 45 10 1 6 hearing loss genitourinary abnormalities #15 tuberous sclerosis spondylolysis c2 c14 dorsal interlaminar rib fusion none halo vest 3 months 6 years fused 30 5 1 6 psychomotor delay #16 c2 spondylolysis c14 dorsal interlaminar fusion none halo vest 3 months 4 years fused 35 10 2 6 recovered full function one year #17 c2 spondylolysis tracheostomy molded cervicothoracic brace none mold brace 4 years 6 years formed c2 posterior arches 45 20 1 3 reformed c2 4 years ct parents wish surgery #18 c2 spondylolysis intraoperative traction c13 dorsal rib graft fusion none neck brace 4 months 8 years fused 45 12 2 5 developed c2 posterior elements #19 klippelfeil intraoperative traction oc4 fusion rib graft none molded brace 6 months 1 years fused oc2 dorsally 45 16 1 4 able sit use hands nonsyndromic #20 nf1 resection ventral tumor c36 c45 corpectomies c45 iliac graft c37 orion plate none halo vest 6 weeks 14 years fused 60 15 3 7 recovered 6 weeks works farm #21 nf1 intraoperative traction resect prevertebral tumor c25 kyphectomies c26 anterior fusion iliac crest none halo vest 3 months 2 years fused 45 20 3 5 initial c13 decompression done elsewhere #22 fibromatosis 1 transoral c2 decompression 2 dorsal oc3 fusion loop none brace 3 months 12 years fused 40 12 4 6 age 2 years neck mass resected diagnosis fibromatosis #23 midcervical kyphosis traction c25 lateral mass fusion screws rods rib grafts worse removal initial traction brace 3 months 8 years fused 45 15 7 8 well #24 chiari shm intraoperative traction oc5 rib graft fusion none halo vest 3 months 21 years fused 50 7 2 6 facets atrophied c2 c3 surgery #25 chiari shm intraoperative traction oc5 dorsal fusion loop rib none miami j brace 4 months 22 years fused 55 10 3 6 facets atrophied c24 surgery #26 chordoma c34 1 dorsal lateral c36 fusion 2 c25 anterior fusion iliac bone none miami j brace 6 months 18 years fused 20 12 5 8 weak hands initial surgery elsewhere #27 abc tumor c4 anterior c35 fusion plate bone none miami j brace 4 weeks 12 years fused 40 15 5 8 recurrence sed spondyloepiphyseal dysplasia smd spondylometaphyseal dysplasia joa japanese orthopedic association mri magnetic resonance imaging shm syringohydromyelia nf1 neurofibromatosis type 1 f u follow oi osteogenesis imperfecta ct computed tomography jk junctional kyphosispmid34806157 doi101007 s0038102105409z,0.0
diffusion imaging fornix interconnected limbic deep grey matter linked cognitive impairment multiple sclerosis eur j neurosci 2021 nov 22 doi 101111 ejn15539 online ahead printabstractdiffusion tensor imaging dti volumetric mri shown white matter wm deep grey matter gm abnormalities limbic system multiple sclerosis ms participants structures like fornix associated cognitive impairment ci ms diffusion metrics often biased partial volume effects cerebrospinal fluid csf due small bundle size intraventricular location errors dti parameter estimation worsen atrophy ms goal evaluate dti parameters volumes fornix well associated deep gm structures like thalamus hippocampus highresolution fluidattenuated inversion recovery flair dti 3t 43 ms patients without ci versus 43 controls fornix thalamus hippocampus displayed atrophy abnormal diffusion metrics fornix showing extensive changes within structures studied mainly ci ms affected fornix volumes diffusion metrics associated thalamic atrophy atypical diffusion metrics interconnected limbic gm larger total lesion volume global brain atrophy lower fractional anisotropy fa higher mean radial diffusivity fornix lower hippocampus fa lower thalamus volume strongly correlated ci ms hippocampus fa thalamus atrophy negatively correlated fatigue longer time since ms symptoms onset respectively flairdti volumetric analyses provided methodologically superior evidence microstructural abnormalities extensive atrophy fornix interconnected deep gm ms associated cognitive deficitspmid34806796 doi101111 ejn15539,0.0
models materials exercise promotion comprehensive multiple sclerosis care completion #39 exercise medicine#39 development process disabil rehabil 2021 nov 2219 doi 101080 0963828820211998662 online ahead printabstractpurpose health care providers highlighted need tools resources support promotion exercise behavior within comprehensive multiple sclerosis ms care study involved final quality improvement evaluation exercise promotion models materials inclusion within settingmethods materials research team distributed paperbased survey containing likert scales open answer questions copies models editing distributed survey among health care providers across united states conducted novel mixedmethods analysis evaluating quantitative qualitative creative dataresults received completed surveys 13 health care providers strongly rated clarity applicability models materials reported major improvements necessary minor improvements specific per comprehensive ms care center feedback indicated exercise medicine models materials guides processes integrated real world practice amending roles responsibilities team members structure per comprehensive ms care centerconclusion paper presents finalized models materials exercise promotion within comprehensive ms care ready tested feasibility efficacy clinical trialimplications rehabilitationhealth care providers require support promote exercise within context comprehensive ms carethe practice models article provide guides regarding promote exercise contextimplementing exercise promotion guides can reduce burden neurologists ensure patients receive exercise support appropriate providersthese guides implemented within context individual care center explicit step step guide care center uniquepmid34802341 doi101080 0963828820211998662,0.0
role vitamins neurodegenerative diseases review cns neurol disord drug targets 2021 nov 19 doi 102174 1871527320666211119122150 online ahead printabstractbackground vitamins micronutrients required boosting immune system managing future infection vitamins involved neurogenesis defense mechanism working neurons metabolic reactions neuronal survival neuronal transmission deficiency leads abnormal functions brain like oxidative stress mitochondrial dysfunction accumulation proteins synuclein plaques neurodegeneration excitotoxicitymethods review compiled various reports collected pubmed scholar google research gate science direct findings evaluated compiled represented manuscriptconclusion deficiency vitamins body causes various neurological disorders like alzheimers disease parkinsons disease huntingtons disease depression discussed role vitamins neurological disorders normal human body depression linked deficiency vitaminc vitamin b case alzheimers disease lack vitaminb1 b12 vitamina results aplaques similarly parkinsons disease vitamind deficiency leads decrease level dopamine imbalance vitamin d leads accumulation synuclein ms vitaminc vitamind deficiency causes demyelination neurons huntingtons disease vitamin c deficiency decreases antioxidant level enhances oxidative stress disrupts glucose cycle vitamin b5 deficiency huntingtons disease disrupts synthesis acetylcholine hormones brainpmid34802410 doi102174 1871527320666211119122150,1.0
technologysupported acceptance commitment therapy chronic health conditions systematic review metaanalysis behav res ther 2021 nov 12 148103995 doi 101016 jbrat2021103995 online ahead printabstractchronic health conditions chcs common associated functional limitations acceptance commitment therapy act shows promise improving functioning quality life distress across several chcs purpose study conduct systematic review technologysupported act chcs perform metaanalysis functioning act process outcomes multiple databases systematically searched randomized controlled trials total 20 unique studies 2 430 randomized participants included chcs addressed studies chronic pain k 9 obesity overweight k 4 cancer k 3 hearing loss k 1 hiv k 1 multiple sclerosis k 1 tinnitus k 1 internet telephone used technology platforms studies included therapist contact considerable heterogeneity studies random effects metaanalyses found medium effect sizes showing technologysupported act outperformed comparator groups measures function posttreatment hedges g 049 p 0002 followup hedges g 052 p 002 well act process outcomes posttreatment hedges g 048 p 0001 followup hedges g 044 p 0001 technologysupported act shows promise improving function act process outcomes across range chcs recommendations provided optimize technologysupported act chcs prospero registration number crd42020200230pmid34800873 doi101016 jbrat2021103995,0.0
serotonin systemic sclerosis emerging player pathogenesis joint bone spine 2021 nov 17105309 doi 101016 jjbspin2021105309 online ahead printabstractobjectives systemic sclerosis ssc complex autoimmune disease characterized multiple organ fibrosis vasculopathy experimental clinical evidence indicates serotonin crucially involved fibrotic process mediates vascular manifestations raynauds phenomenon rp pulmonary arterial hypertension pah key features ssc review summarize current knowledge potential contribution serotonin ssc pathogenesis provide rationale investigation molecule therapeutic targetmethods medline cochrane databases searched inception april 2021 using search terms systemic sclerosis scleroderma raynaud pulmonary arterial hypertension serotoninresults serotonin key molecule array central peripheral functions multifaceted role regulating fibrosis vasculopathy experimental data suggest serotonin drives fibrosis skin visceral organs promotes platelet aggregation induces vasoconstriction increases pulmonary vascular resistance earlier human trials regarding drugs inhibit serotonin signaling produced mixed results however recent advances understanding underlying molecular mechanisms help identify novel therapeutics targeting serotonin pathway inform future clinical trialsconclusions serotonin may mediator fibrosis vasculopathy exploration potential role serotonin ssc justifiedpmid34800695 doi101016 jjbspin2021105309,0.0
progressive multifocal leukoencephalopathy sphingosine 1phosphate receptor modulators used multiple sclerosis updated review literature j neurol 2021 nov 20 doi 101007 s00415021109101 online ahead printabstractobjective progressive multifocal leukoencephalopathy pml serious viral infection associated diseasemodifying therapies dmt multiple sclerosis ms including sphingosine 1phosphate receptor s1pr modulators objective review investigate characteristics pml ms patients associated drugs s1pr modulatormethods conducted literature review analysis 24 patients 12 publications pubmed scopus embase descriptive analysis study characteristics pml associated fingolimod related s1pr modulator group dmtresults total 24 cases pml ms patients treated fingolimod identified 21 cases contained data regarding changes expanded disability status scale edss one case pml association ozanimod treatment clinical trial also identified pml cases associated fingolimod mean age time pml diagnosis 5091 115 years patients treated fingolimod 24 months compared patients improved stable terms edss symptomatic management pml nonimproved groups significantly older fatalities either group reported followup periodconclusion incidence pml appears extremely low ms patients treated s1pr modulators risk pml increases increase duration treatment s1pr modulators like fingolimod increased age time pml diagnosis associated worse prognosispmid34800168 doi101007 s00415021109101,0.0
correction treatment response scoring systems assess longterm prognosis selfinjectable dmts relapsingremitting multiple sclerosis patients j neurol 2021 nov 20 doi 101007 s0041502110906x online ahead printno abstractpmid34800172 doi101007 s0041502110906x,0.0
multiple sclerosis impairment scale brain mri secondary progressive multiple sclerosis acta neurol scand 2021 nov 19 doi 101111 ane13554 online ahead printabstractobjective examine multiple sclerosis impairment scale msis secondary progressive ms spms relation expanded disability status scale edss magnetic resonance imaging mri outcomes mobilitymethods observational singlecenter study 68 secondary progressive multiple sclerosis spms patients examined msis edss functional mobility tests upper lower extremities multimodal mri participants edss 35 decline daily activities last year unrelated relapses 6month confirmed disability progressionresults mean disease duration 231 83 years mean age 544 81 years msis edss corresponding motor cerebellar sensory subscores correlated p 0001 motor subscores msis correlated stronger timed25footwalk t25fw pyramidal functional system score fss p 03 edss stronger correlation t25fw total msis score p 01 msis cerebellar subscore correlated stronger 9hole peg test 9hpt cerebellar fss p 04 sensory msis subscore also showed correlation 9hpt contrast sensory fss p 006 msis subscores stronger correlations mri volumetry measures fss scores lesion volume putamen thalamus corpus callosum volumetry p 000100017 conclusion patients spms msis correlated functional motor tests msis showed stronger correlations atrophy central nervous system areas may sensitive scale cerebellar sensory function edsspmid34799851 doi101111 ane13554,0.0
clinical reasoning 57yearold man stepwise progressive paraparesis sensory loss urinary retention constipation neurology 2021 nov 19101212 wnl0000000000013090 doi 101212 wnl0000000000013090 online ahead printabstractwe present case 57yearold man protein s deficiency left leg deep vein thrombosis dvt five years prior developed stepwise progressive bilateral lower limb weakness numbness paresthesia gait imbalance hesitancy micturition constipation setting recurrent left common femoral dvt treated apixaban symptoms amplified valsalva corticosteroids postlumbar puncture longitudinally extensive midthoracic t2hyperintense lesion extending conus associated hazy holocord enhancement magnetic resonance imaging mri raising suspicion spinal dural arteriovenous fistula sdavf initial digital subtraction angiography dsa negative sdavf however cerebral spinal fluid csf herpes simplex virus hsv 2 positive treated antiviral therapy unfortunately continued worsen despite treatment repeat neuroimaging twelve months initial presentation demonstrated persistent lower thoracic conus lesion addition cauda equina enhancement subtle dorsal t2hypointense flow voids raised red flags eg lack clinical prodrome herpetic rash csf pleocytosis rostral extent lesion suggested hsv2 nucleic acid detection perhaps unrelated neurological syndrome given high index suspicion sdavf repeated spinal vascular imaging spinal mra demonstrated dilated right dorsal perimedullary veins t10 t11 repeat dsa revealed right t10 sdavf microsurgical treatment rather embolization fistula successful without complication significant improvement motor sphincter lesser extent sensory function residual gait imbalance inpatient rehabilitation three weeks postoperativelypmid34799458 doi101212 wnl0000000000013090,0.0
epsteinbarr virus nuclear antigen 2 extensively rewires human chromatin landscape autoimmune risk loci genome res 2021 nov 19 doi 101101 gr264705120 online ahead printabstractthe interplay environmental genetic factors plays key role development many autoimmune diseases particular epsteinbarr virus ebv established contributor multiple sclerosis lupus disorders previously showed ebv nuclear antigen 2 ebna2 transactivating protein occupies half risk loci set seven autoimmune disorders examine mechanistic roles played ebna2 loci genomewide scale globally examined gene expression chromatin accessibility chromatin looping ebna2 binding b cell line 1 uninfected 2 infected strain ebv lacking ebna2 3 infected strain expresses ebna2 identified 400 ebna2dependent differentially expressed human genes 5000 ebna2 binding events human genome atacseq analysis revealed 2000 regions human genome ebna2dependent chromatin accessibility hichip data revealed 1700 regions ebna2 altered chromatin looping interactions autoimmune genetic risk loci highly enriched sites ebna2dependent chromatinaltering events present examples autoimmune risk genotypedependent ebna2 events nominating genetic risk mechanisms autoimmune risk loci zmiz1 taken together results reveal important interactions host genetic variation ebna2driven disease mechanisms study highlights critical role ebna2 rewiring human gene regulatory programs rearrangement chromatin landscape nominates interactions components genetic mechanisms influence risk multiple autoimmune diseasespmid34799401 doi101101 gr264705120,0.0
kinetics myelin breakdown products labeling study patients progressive multiple sclerosis clin transl sci 2021 nov 19 doi 101111 cts13181 online ahead printabstractthe majority disease modifying therapies multiple sclerosis ms reduce inflammation target remyelination development remyelinating therapies will benefit method quantify myelin kinetics patients ms labeled myelin vivo deuterium modeled kinetics myelin breakdown products galactosylceramide galc noctadecanoylsulfatide nosulf five patients ms received 120 ml 70 d2 o daily 70 days compared six healthy subjects previously received procedure mass spectrometry compartmental modeling used quantify turnover rate galc nosulf cerebrospinal fluid csf turnover rate constants fractions galc nosulf nonnegligible turnover 000186 000714 respectively healthy subjects patients ms turnover halflife galc nosulf calculated 373 days 965 days respectively effect ms nosulf 494 lower fraction nonnegligible turnover pronounced compared effect galc turnover 183 lower fraction nonnegligible turnover kinetics myelin breakdown products csf different patients ms compared healthy subjects may caused slower myelin production patients higher level degradation stable component myelin likely combination two processes labeling myelin breakdown products useful method can used quantify myelin turnover patients progressive ms can therefore used proofofconcept studies remyelination therapiespmid34799987 doi101111 cts13181,1.0
vivo detection damage multiple sclerosis cortex cortical lesions using noddi j neurol neurosurg psychiatry 2021 nov 19jnnp2021327803 doi 101136 jnnp2021327803 online ahead printabstractobjective characterise vivo microstructural abnormalities multiple sclerosis ms normalappearing na cortex cortical lesions cls relations clinical phenotypes disability using neurite orientation dispersion density imaging noddi methods one hundred seventytwo patients ms 101 relapsingremitting multiple sclerosis rrms 71 progressive multiple sclerosis pms 62 healthy controls hcs underwent brain 3t mri brain cortex cls segmented threedimensional t1weighted double inversion recovery sequences using noddi diffusionweighted sequence intracellular volume fraction icv_f orientation dispersion index odi assessed na cortex cls default optimised parallel diffusivity cortex d 17 12 m2 ms respectively results na cortex patients ms significantly lower icv_f versus hcs cortex d values false discovery rate fdr p 0001 cls showed significantly decreased icv_f odi versus na cortex hcs patients ms d values fdrp 0008 patients pms versus rrms significantly decreased na cortex icv_f odi fdrp0050 fdrp0032 d 17 m2 ms cl microstructural differences found ms clinical phenotypes ms na cortex icv_f odi significantly correlated disease duration clinical disability lesion burden global regional brain atrophy r 051 071 fdrp 0001 0045 conclusions significant neurite loss occurs ms na cortex cls show neurite density reduction reduced odi suggesting simplification neurite complexity noddi relevant investigate vivo heterogeneous pathology affecting ms cortexpmid34799405 doi101136 jnnp2021327803,0.0
innovative approach modelling optimal treatment sequence patients relapsingremitting multiple sclerosis implementation validation impact decisionmaking approach adv ther 2021 nov 18 doi 101007 s12325021019755 online ahead printabstractintroduction innovative computational model developed address challenges regarding evaluation treatment sequences patients relapsingremitting multiple sclerosis rrms concept virtual physician observes assesses patients time describe implementation validation model apply framework case study determine impact different decisionmaking approaches optimal sequence diseasemodifying therapies dmts associated outcomesmethods patientlevel discrete event simulation des used model heterogeneity disease trajectories outcomes evaluation dmt options implemented markov model representing patients disease outcomes included lifetime costs quality life des markov models underwent internal external validation analyses optimal treatment sequence patient based several decisionmaking criteria treatment sequences compared current treatment guidelinesresults internal validation indicated model outcomes natural history consistent input parameters used inform model costs quality life outcomes successfully validated published reference models whereas decisionmaking criterion generated different optimal treatment sequence cladribine tablets dmt common treatment sequences choosing treatments basis minimising disease progression number relapses possible improve current treatment guidelines however treatment sequences costly maximising costeffectiveness resulted lowest costs also associated worst outcomesconclusions model robust generating outcomes consistent published models studies also able identify optimal treatment sequences based different decision criteria innovative modelling framework potential simulate individual patient trajectories current treatment landscape may useful treatment switching treatment positioning decisions rrmspmid34796464 doi101007 s12325021019755,0.0
amygdala network reorganization mediates theory mind performances multiple sclerosis j neurosci res 2021 nov 19 doi 101002 jnr24986 online ahead printabstracttheory mind tom seems affected multiple sclerosis ms mri studies suggested role amygdala social cognitive performances therefore explored role amygdala network tom using multimodal mri approach ms patients impaired tom showed contradictory dysexecutive neuropsychological profile therefore compared neural networks involved tom executive functions efs twenty patients relapsingremitting ms 15 matched healthy controls selected tom faux pas test mind stories efs assessed within outside scanner subjects underwent battery neuropsychological tests multimodal mri structural diffusion imaging functional restingstate taskbased sequences used analyze role connections amygdala tom functioning cognitive tom performances similar patients controls restingstate data revealed decreased connectivity left amygdala frontal areas patients compared controls p 00001 taskbased functional mri patients demonstrated increased connectivity amygdala several cerebellar left temporal regions p 005 microstructural alterations left amygdala left temporal regions associated increased functional connectivity within pathway r 074 p 001 overlap observed functional networks involved tom efs study demonstrates connectivity recruitment amygdala cerebellar temporal regions ms patients reach preserved tom performance microstructural abnormalities related compensatory network finally different networks involved efs tompmid34796987 doi101002 jnr24986,0.0
central vein sign putative diagnostic marker multiple sclerosis acta neurol scand 2021 nov 18 doi 101111 ane13553 online ahead printabstractthe presence central vein sign cvs introduced biomarker diagnosis multiple sclerosis ms shown ability accurately differentiate ms white matter diseases ms mimics following development susceptibilitybased magnetic resonance venography allowed vivo detection cvs standard cvs definition established introducing 40 rule assesses number ms lesions cvs fraction total number lesions differentiate ms lesions types lesions 50 rule threelesion criteria sixlesion criteria later introduced defined rules high levels sensitivity specificity accuracy differentiating ms diseases recognized magnetic resonance imaging ms magnims group consortium ms centers task force north american imaging multiple sclerosis cooperative even provided statements recommendations aiming refine standardize evaluate cvs ms herein review existing literature cvs evaluate added value diagnosis ms usefulness differentiating vasculopathies also review histopathology cvs identify available automated cvs assessment methods well define role vascular comorbidities diagnosis mspmid34796472 doi101111 ane13553,0.0
correction vaccine considerations multiple sclerosis covid19 era adv ther 2021 nov 18 doi 101007 s12325021019675 online ahead printno abstractpmid34792786 doi101007 s12325021019675,0.0
robust t cell responses anticd20 treated patients following covid19 vaccination prospective cohort study clin infect dis 2021 nov 17ciab954 doi 101093 cid ciab954 online ahead printabstractbackground patients treated anticd20 therapy particularly risk developing severe covid19 however little known regarding covid19 vaccine effectiveness populationmethods prospective observational cohort study assesses humoral tcell responses vaccination 2 doses mrnabased covid19 vaccines patients treated rituximab rheumatic diseases ocrelizumab multiple sclerosis n37 compared immunocompetent individuals n22 results sarscov2specific antibodies detectable 694 patients levels significantly lower compared controls seroconverted contrast antibodies spike s specific cd4+ t cells equally detected immunocompetent anticd20 treated patients 8590 mostly th1 phenotype response rates sspecific cd8 + t cells higher ocrelizumab 962 rituximabtreated patients 818 compared controls 667 sspecific cd4 + cd8 + t cells polyfunctional expressed activation markers patients controls followup three ms patients without sarscov2specific antibody response mild breakthrough infection one detectable sspecific t cells vaccinationconclusions study suggests patients anticd20 treatment able mount potent tcell responses mrna covid19 vaccines despite impaired humoral responses play important role reduction complications severe covid19pmid34791081 doi101093 cid ciab954,0.0
review mendelian randomization amyotrophic lateral sclerosis brain 2021 nov 16awab420 doi 101093 brain awab420 online ahead printabstractamyotrophic lateral sclerosis als relatively common rapidly progressive neurodegenerative disease majority cases thought determined complex geneenvironment interaction exponential growth number performed genomewide association studies gwas combined advent mendelian randomization mr opening significant new opportunities identify environmental exposures increase decrease risk als discoveries potential shape new therapeutic interventions however rigorous methodological standards must applied performance mr performed review mr studies performed als date identified 20 mr studies including evaluation physical exercise adiposity cognitive performance immune function blood lipids sleep behaviours educational attainment alcohol consumption smoking type 2 diabetes mellitus evaluated study using gold standard methodology supported mr literature strobemr checklist discrepancies exist mr studies suggest underlying reasons number studies conclude causal link blood lipids risk als replication across different datasets even different populations adds confidence putative risk factors smoking immune function mr studies provided cause doubt highlight use positive control analyses choosing exposure snps make mr instrument use snp clumping avoid false positive results due snps linkage importance multiple testing correction discuss implications survival bias study late age onset diseases als make recommendations mitigate potentially important confounder mr useful als field high methodological standards must applied ensure reproducibility mr already impactful tool poor quality studies will lead incorrect interpretations field includes nonstatisticians wasted resources missed opportunitiespmid34791088 doi101093 brain awab420,0.0
restingstate eeg reveals four subphenotypes amyotrophic lateral sclerosis brain 2021 nov 17awab322 doi 101093 brain awab322 online ahead printabstractamyotrophic lateral sclerosis als devastating disease characterised primarily motor system degeneration clinical evidence cognitive behavioural change 50 cases als clinically biologically heterogeneous subgrouping currently undertaken using clinical parameters site symptom onset bulbar spinal burden disease based modified el escorial research criteria genomics familial disease however exception genomics subcategories take account underlying disease pathobiology fully predictive disease course prognosis recently shown restingstate eeg can reliably quantitatively capture abnormal patterns motor cognitive network disruption als network disruptions identified across multiple frequency bands using measures neural activity spectral power connectivity comodulation activity amplitude envelope correlation synchrony imaginary coherence sourcelocalised brain oscillations highdensity eeg using datadriven methods similarity network fusion spectral clustering now undertaken clustering analysis identify disease subphenotypes determine whether different patterns disruption predictive disease outcome show als patients n 95 can subgrouped four phenotypes distinct neurophysiological profiles clusters characterised varying degrees disruption somatomotor band synchrony frontotemporal band neural activity lband synchrony frontoparietal lband comodulation networks reliably correlate distinct clinical profiles different disease trajectories using indepth stability analysis show clusters statistically reproducible robust remain stable reassessment using followup eeg session continue predict clinical trajectory disease outcome data demonstrate novel phenotyping using neuroelectric signal analysis can distinguish disease subtypes based exclusively different patterns network disturbances patterns may reflect underlying disease neurobiology identification als subtypes based profiles differential impairment neuronal networks clear potential future stratification clinical trials advanced network profiling als can also underpin new therapeutic strategies based principles neurobiology designed modulate network disruptionpmid34791079 doi101093 brain awab322,0.0
caregiver involvement ms duty disruption neurol ther 2021 nov 18 doi 101007 s40120021002994 online ahead printabstractmultiple sclerosis ms complex condition numerous physical cognitive emotional symptoms may necessitate significant permanent lifestyle changes people multiple sclerosis pwms caregivers families meaning important contemporary neurological practice consider including families caregivers management ms however existing evidence suggests family involvement always beneficial example can exert either strong positive negative influence ability pwms achieve optimal outcomes treatment disease management paper based live debate neurologists pwms examines current perceptions constructive involvement families caregivers consultations management ms reveals several areas additional studies warranted shared decisionmaking ms historically collaboration solely healthcare professionals hcps pwms pwms now frequently accompanied appointments support person paper encourages hcps understand dynamics pwms support person individualize consultations information accordingly family caregiver involvement provision care pwms needs benefit discretion pwms support families pwms although important may effectively appropriately delivered channels outside clinical setting educating hcps current patient experience enable provide improved personalized care will ensure mutualistic patientcentred relationship pwms will help optimize outcomes communication tools may also facilitate interactionspmid34792783 doi101007 s40120021002994,0.0
design validation expanded disability status scale model multiple sclerosis eur neurol 2021 nov 17110 doi 101159 000519772 online ahead printabstractintroduction aimed develop validate expanded disability status scale edss model clinical optical coherence tomography oct magnetic resonance imaging mri measuresmethods sixtyfour multiple sclerosis ms patients underwent peripapillary retinal nerve fiber layer segmented macular layers evaluation oct spectralis heidelberg engineering brain parenchymal fraction quantified freesurfer cervical spinal cord sc volume assessed manually guided spinal cord toolbox software analysis edss neuroradiological oct assessment carried within 3 months oct parameters calculated average nonoptic neuritis eyes case patient previous value fellow nonon eye taken brain lesion volume sex age disease duration history diseasemodifying treatment 1st 2nd line diseasemodifying treatments tested covariables edss scoreresults edss values correlated patients age r 0543 p 0001 sc volume r 0301 p 0034 ganglion cell layer gcl r 0354 p 0012 using correlations ordinal regression model express probability diverse edss scores designed highest probable nagelkerke r2 433 using edss cutoff point 40 dichotomous model compared cutoff 20 permits inclusion gcl disability predictor addition age scconclusions ms disability measured edss agedependent magnitude partly conditioned sc gcl studies assessing paraclinical disability predictors neededpmid34788755 doi101159 000519772,0.0
parkinson#39 s disease covid19 systematic review metaanalysis neurol sci 2021 nov 17 doi 101007 s10072021057564 online ahead printabstractbackground patients parkinsons disease pd higher risk covid19 infection older age goal study update pooled prevalence covid19 infection patients pdmethods two researchers systematically searched pubmed scopus embase web science google scholar also gray literature including references included studies published september 2021 extracted data regarding total number participants first author publication year country origin mean age number covid19 symptoms hospitalization deathresults found 1693 articles literature search deleting duplicates 798 remained thirty articles remained metaanalysis pooled prevalence covid19 infection pd cases 5 95ci 46 i2 981 p 0001 pooled prevalence fever cases pd 4 95ci 26 i2 96 p 0001 pooled prevalence cough cases pd 3 95ci 24 i2 959 p 0001 pooled prevalence hospitalization cases covid19 infection 49 95ci 2952 i2 935 p 0001 pooled prevalence mortality covid19 cases 12 95ci 1014 i2 976 p 0001 conclusion results systematic review metaanalysis show pooled prevalence covid19 infection pd cases 5 besides hospitalization mortality rates 49 12pmid34787753 doi101007 s10072021057564,0.0
routine gadolinium use mri followup multiple sclerosis counterpointgadolinium always used assess disease activity ajr j roentgenol 2021 nov 17 doi 102214 ajr2127069 online ahead printno abstractpmid34786958 doi102214 ajr2127069,0.0
methyl butyrate alleviates experimental autoimmune encephalomyelitis regulates balance effector t cells regulatory t cells inflammation 2021 nov 16 doi 101007 s10753021015968 online ahead printabstractmultiple sclerosis ms autoimmune disease central nervous system cns characterized demyelinating neuropathy etiology ms yet clear treatment remains major medical challenge search drugs can effectively treat experimental autoimmune encephalomyelitis eae animal model ms also hope explore possible pathogenesis present study investigated whether methyl butyrate mb alleviate eae potential mechanisms eae mice found administration mb effective alleviating clinical signs improving histopathological manifestations cns cns intestinal lamina propria observed fewer effector t cells including th1 th17 mbtreated group mb also increased proportion regulatory t cells secretion il10 peripheral immune organs vitro mb led suppression th1 cells promotion regulatory t cells differentiation given mb direct effect th17 cell differentiation vitro hypothesized mb suppressed th17 cells indirectly inhibiting secretion il6 later confirmed vitro vivo addition found mb treatment upregulated maf gene expression mice explained promotion il10 secretion findings suggest mb may provide new ideas study mechanism ms positive implications new drug developmentpmid34786625 doi101007 s10753021015968,1.0
administrative data observational research multiple sclerosis opportunities challenges mult scler 2021 nov 1713524585211055787 doi 101177 13524585211055787 online ahead printno abstractpmid34787000 doi101177 13524585211055787,0.0
routine gadolinium use mri followup multiple sclerosis pointthe role leptomeningeal enhancement ajr j roentgenol 2021 nov 17 doi 102214 ajr2126999 online ahead printno abstractpmid34786959 doi102214 ajr2126999,0.0
prevalence multiple sclerosis ms iran systematic review metaanalysis neurol sci 2021 nov 17 doi 101007 s1007202105750w online ahead printabstractbackground prevalence multiple sclerosis ms increasing worldwide iran exception prevalence reported differently various provinces designed systematic review metaanalysis estimate pooled prevalence ms iranmethods two researchers systematically searched scientific information database sid pubmed scopus embase web science google scholar also searched references included studies conference abstracts published april 2021 search strategy included mesh text words multiple sclerosis sclerosis multiple sclerosis disseminated disseminated sclerosis ms multiple sclerosis multiple sclerosis acute fulminating prevalence prevalences period prevalence prevalence period point prevalence point prevalences prevalence point iran islamic republic iran results literature search revealed 2817 articles deleting duplicates 2184 remained systematic review 34 studies included prevalence highest tehran lowest khuzestan sistanbaluchestan provinces pooled prevalence 0001 95 ci 00000001 i20 p0001 conclusion results study show pooled prevalence ms iran 100 100 000 high prevalence provinces increases dramaticallypmid34787755 doi101007 s1007202105750w,0.0
patientreported outcomes associated transition secondary progressive multiple sclerosis qual life res 2021 nov 16 doi 101007 s11136021030346 online ahead printabstractpurpose investigate patientreported outcome pro measures patients relapsingremitting multiple sclerosis rrms transition secondary progressive multiple sclerosis spms methods subjects enrolled comprehensive longitudinal investigation multiple sclerosis brigham womens hospital climb completed pro measures rrms spms phases identified n 52 pro measures medical outcomes study shortform 36 health survey sf36 modified fatigue impact scale mfis center epidemiologic studies depression scale cesd two control groups rrms climb patients progress spms identified based different matching criteria related age sex disease duration expanded disability status scale edss summary statistics pro calculated last rrms measurement first spms measurement change transition calculated using paired ttest patients transitioned compared control groups using linear regression adjust age disease duration edss mixed model account matching random effect matched groupresults patients transitioned rrms spms noticeable deficits terms quality life qol fatigue visit prior transition patients worsened terms sf36 role physical 36 66 07 social functioning 37 64 10 physical component summary 23 45 01 transition rrms spms patients transitioned compared matched subjects worse scores several outcomes including physical functioning adjusted mean difference 108 141 75 physical component summary 52 93 10 fatigue 89 17 161 depression 31 03 59 conclusions patients period closely preceding transition rrms spms worse physical qol fatigue compared subjects remain rrmspmid34783972 doi101007 s11136021030346,0.0
healthcare professionals#39 involvement breaking bad news newly diagnosed patients motor neurodegenerative conditions qualitative study disabil rehabil 2021 nov 16114 doi 101080 0963828820212002436 online ahead printabstractpurpose research breaking bad news bbn healthcare mostly focused doctorpatient interaction single consultation however increasingly recognised bbn wider process also involves healthcare professionals qualitative study explored nonmedical1 healthcare professionals involvement bbn newly diagnosed patients motor neurodegenerative conditions ukmaterials methods 19 healthcare professionals working people motor neurone disease multiple sclerosis parkinsons disease huntingtons disease took part individual semistructured interviews analysed using thematic analysisresults four themes constructed dealing diagnostic aftermath unpacking diagnosis breaking bad news balancing act empowering patients regain control health lives participants reported broadly involved bbn supporting patients negative diagnostic experiences reiterating diagnostic information helping patients understand impact condition challenges effectively breaking bad news difficult conversations help empower patients also emphasisedconclusions bbn critical challenging aspect healthcare professionals clinical work newly diagnosed patients motor neurodegenerative conditions besides providing information bbn perceived way educate patients encourage make decisions prepare futureimplications rehabilitationbreaking bad news potentially underrecognised significant aspect neurorehabilitation neurodegenerative conditionslistening patients stories long occasionally unsatisfactory diagnostic journey allowing express frustration can critical regaining patients trust building relationship themnewly diagnosed patients always received adequate information condition diagnosis might understood retained information therefore essential patients understanding condition assessed misconceptions cleared appropriate information nature impact diagnosis providedirrespective length experience breaking bad news perceived multifaceted challenging stressful emotionally demanding taskformal support specialised training breaking bad news addresses incurable unpredictable progressive nature motor neurodegenerative conditions help professionals challenging taskpmid34783624 doi101080 0963828820212002436,0.0
dehydrocholesterol reductase 24 dhcr24 medicinal chemistry pharmacology novel therapeutic options curr med chem 2021 nov 15 doi 102174 0929867328666211115121832 online ahead printabstractduring last decade understanding biological functions cholesterol biosynthesis intermediates changed significantly particularly enzyme sterol dehydrocholesterol reductase 24 dhcr24 taken center stage potential drug target inhibition dhcr24 leads accumulation endogenous biologically active metabolite cholesta5 24dien3ol desmosterol desmosterol endogenous agonist liver x receptor lxr lxr master regulator lipid metabolism involved numerous pathophysiological processes inflammation atherosclerosis cancer diabetes mellitus dm multiple sclerosis ms nonalcoholic steatohepatitis nash progression viral infections now selective pharmacological targeting lxr without activating sterolresponse element binding proteins srebp thereby boosting endogenous lipid biosynthesis achieved turn selective lxr receptor agonists leveraging beneficial activation yet reached clinic therefore using potent selective inhibitors dhcr24 leading accumulation endogenous desmosterol promising alternative strategy selective activation lxr summarize present landscape novel lead structures targeting dhcr24 covering steroidal enzyme inhibitors eg 20 25diazacholesterol sh42 well nonsteroidal scaffolds eg amiodarone triparanol explain molecular mechanisms dhcr24 inhibition lxr activation discuss possible therapeutic applications underpin dhcr24 upcoming promising drug targetpmid34781860 doi102174 0929867328666211115121832,0.0
restless legs syndrome related factors people multiple sclerosis turkey neurol res 2021 nov 1518 doi 101080 0161641220212000822 online ahead printabstractobjective restless legs syndrome one reported sleep disorders multiple sclerosis ms study aims investigate possible factors related occurrence severity restless legs syndrome persons ms pwms comparing healthy controlsmethods casecontrol study included 447 pwms 57 healthy controls demographic clinical data gender age duration education body mass index marital status disease duration ms type recorded neurological disability assessed expanded disability status scale restless legs syndrome rating scale used assess severity restless legs syndromeresults prevalence restless legs syndrome pwms 133 298 3 49 healthy controls p 0001 significant difference groups terms gender body mass index ms type p 005 patients restless legs syndrome advanced age longer disease duration higher expanded disability status scale scores patients without restless legs syndrome p 005 correlation restless legs syndrome severity age expanded disability status scale score disease duration statistically significant p 005 conclusions study shown presence restless legs syndrome high persons ms compared healthy controls advanced age disease duration higher disability level related increased rate restless legs syndrome persons ms especially highfrequency symptomspmid34781840 doi101080 0161641220212000822,0.0
immigrant family kii amyotrophic lateral sclerosis#x2f parkinsonismdementia complex neurol sci 2021 nov 15 doi 101007 s10072021057377 online ahead printabstractobjectives amyotrophic lateral sclerosis parkinsonismdementia complex als pdc unique endemic guam island usa kii peninsula japan papua state indonesia pathomechanism als pdc remains solved although interaction environmental factors genetic background plausible first autopsyproven immigrant family als pdc kii peninsulamethods daughter father immigrated high incident area outside kii peninsula father developed als 18 years later immigration daughter also developed als 65 years immigration showed pure als phenotype without parkinsonism dementiaresults daughter diagnosed neuropathologically kii als pdc multiple proteinopathies tauopathy synucleinopathy tdp43 proteinopathy gene analysis familial alsrelated genes including c9orf72 showed mutationdiscussion findings immigrant family established certain environmental factors play critical role pathogenesis kii als pdcpmid34779964 doi101007 s10072021057377,0.0
novel tfg mutation korean family alphasynucleinopathy amyotrophic lateral sclerosis mov disord 2021 nov 15 doi 101002 mds28857 online ahead printabstractbackground tropomyosinreceptor kinase fused gene tfg functions regulator intracellular protein packaging trafficking endoplasmic reticulum exit sites tfg recently proposed cause multisystem proteinopathyobjectives describe korean family presenting parkinsons disease amyotrophic lateral sclerosis caused novel variant tfg c1148 g parg383his methods collected clinical genetic dopamine transporter imaging nerve conduction electromyography data seven subjects verify pathogenicity r383h variant studied cell viability abnormal aggregation synuclein tar dnabinding protein 43 tdp43 hela cells expressing r383htfgresults clinical phenotypes r383htfg mutation varied five family members one parkinsons disease three subclinical parkinsonism one proband amyotrophic lateral sclerosis individual multiple system atrophy probands paternal cousin tfg genotype confirmed due unavailability samples vitro studies showed r383htfg overexpression impaired cell viability cells coexpressing r383htfg synuclein insoluble synuclein aggregates increased concentration secreted cells colocalized r383htfg levels cytoplasmic insoluble aggregates tdp43 increased hela cells expressing r383htfg colocalized r383htfgconclusions clinical vitro studies supported pathogenic role novel tfg mutation synucleinopathy tdp43 proteinopathy findings expand phenotypic spectrum tfg suggest pivotal role endoplasmic reticulum dysfunction neurodegeneration 2021 international parkinson movement disorder societypmid34779525 doi101002 mds28857,0.0
patterns balance loss systematic perturbations parkinson#39 s disease multiple sclerosis neurorehabilitation 2021 nov 10 doi 103233 nre210200 online ahead printabstractbackground multiple sclerosis ms parkinsons disease pd may affect balance differently however studies compared loss balance lob patterns following multidirectional perturbationsobjective 1 determine reliability lob ratings following standardized manual perturbations 2 compare lob ratings ms pd healthy control hc groups following perturbations upper lower torso anterior posterior right left rotational directionsmethods 1 reviewers rated videotaped lob following perturbations applied 4 clinicians 610 hcs 2 three groups 64 ms 42 pd 32 hc received perturbations lob ratings following perturbations analyzed using twofactor mixed anovas magnitude prevalenceresults 1 lob ratings showed moderate good icc good excellent agreement 2 ms group showed greater magnitude prevalence lob pd hc groups p 001 groups showed greater lob right left versus anterior posterior perturbations p 01 pd showed greater lob perturbations upper versus lower torso ms hc showed greater lob posterior versus anterior perturbationsconclusions reliable rating scale showed differences patterns lob following manual perturbations ms pd hc clinically accessible reliable assessment lob facilitate targeted perturbationbased interventions reduce falls vulnerable populationspmid34776428 doi103233 nre210200,0.0
anorectal dysfunction multiple sclerosis patients pilot study effect individualized rehabilitation approach neurorehabilitation 2021 nov 7 doi 103233 nre210226 online ahead printabstractbackground anorectal dysfunction ard especially bowel incontinence frequently compromises quality life multiple sclerosis ms patients effect rehabilitation procedures clearly establishedobjective determine effect individualized rehabilitation approach bowel incontinence anorectal pressuresmethods ms patients ard underwent 6months individually targeted biofeedback rehabilitation high resolution anorectal manometry hram st marks fecal incontinence scores smis completed prior rehabilitation 10 weeks supervised physiotherapy 3 months selftreatmentresults ten patients 50 completed study repeated measures analysis variance anova demonstrated significant improvement smis questionnaire time 1400 baseline vs 970 supervised physiotherapy vs 930 selftreatment p 0005 significant improvements time noted hram readings maximal pressure 4985 mmhg baseline vs 5760 supervised physiotherapy vs 6088 selftreatment p 058 pressure endurance 3641 vs 4689 vs 4995 p 053 resting pressure 5583 vs 5269 vs 5184 p 0704 area curve 2300 vs 5208 vs 5019 p 016 conclusions proposed individualized rehabilitation program supports positive overall effect anorectal dysfunction ms patientspmid34776431 doi103233 nre210226,0.0
lateonset neuromyelitis optica spectrum disorder case series iran rev neurol paris 2021 nov 11s00353787 21 007335 doi 101016 jneurol202108006 online ahead printabstractintroduction neuromyelitis optica spectrum disorder nmosd disabling autoimmune disease central nervous system can start ages 50 called lateonset nmosd lonmosd data disorder sparse crosssectional study patient characteristics disease studied lonmosd patients tertiary center tehran studied 2016 2020case reports eight patients identified half men diagnostic delay timelapse three years mean 062 sd 106 significantly shorter earlyonset patients seven patients 875 tested positive aqp4igg significantly higher compared earlyonset patients pvalue001 four patients 50 transverse myelitis optic neuritis presenting symptoms three 38 just myelitis one 12 optic neuritisconclusion discrepancy regarding different aspects lonmosd studies needed clarify subject order enhance diagnosis treatmentpmid34776261 doi101016 jneurol202108006,0.0
immune checkpoint ligandbioengineered schwann cells antigenspecific therapy experimental autoimmune encephalomyelitis adv mater 2021 nov 13e2107392 doi 101002 adma202107392 online ahead printabstractfailure establish immune tolerance leads development autoimmune disease ability regulate autoreactive t cells without inducing systemic immunosuppression represents major challenge develop new strategies treat autoimmune disease describe translational method bioengineering programmed deathligand 1 cluster differentiation 86functionalized mouse schwann cells prevent ameliorate multiple sclerosis established mouse models chronic relapsingremitting experimental autoimmune encephalomyelitis eae show intravenous administration immune checkpoint ligandfunctionalized mouse schwann cells modifies course disease ameliorates eae found bioengineered mouse schwann cells inhibit differentiation myelinspecific helper t cells pathogenic t helper type 1 type 17 cells promote development tolerogenic myelinspecific regulatory t cells resolve inflammatory cns microenvironments without inducing systemic immunosuppression article protected copyright rights reservedpmid34775659 doi101002 adma202107392,1.0
abuse dependence potential sphingosine1phosphate s1p receptor modulators used treatment multiple sclerosis review literature public data psychopharmacology berl 2021 nov 13 doi 101007 s00213021060116 online ahead printabstractabuse misuse prescription drugs remains ongoing concern usa worldwide thus centrally active new drugs must assessed abuse dependence potential sphingosine1phosphate s1p receptor modulators used primarily treatment multiple sclerosis among new s1p receptor modulators siponimod ozanimod ponesimod recently approved usa european union eu countries review literature public data undertaken assess potential abuse s1p receptor modulators including ozanimod siponimod ponesimod fingolimod well several similar compounds development s1p receptor modulators shown chemical pharmacological similarity known drugs abuse shown abuse dependence potential animal models subjective effects reinforcement physical dependence adverse event profiles demonstrating effects interest individuals abuse drugs sedative stimulant moodelevating hallucinogenic effects addition reports actual abuse misuse dependence identified scientific literature fingolimod market since 2010 usa 2011 eu overall data suggest s1p receptor modulators associated significant potential abuse dependence consistent unscheduled status usa internationallypmid34773483 doi101007 s00213021060116,0.0
t cells hopedfor savior sarscov2 vaccination cd20depleting antibody therapy commentary quot discordant humoral t cell immune responses sarscov2 vaccination people multiple sclerosis anticd20 therapyquot ebiomedicine 2021 nov 10 74103692 doi 101016 jebiom2021103692 online ahead printno abstractpmid34773893 doi101016 jebiom2021103692,0.0
laminin regulates oligodendrocyte development myelination glia 2021 nov 12 doi 101002 glia24117 online ahead printabstractoligodendrocytes cells myelinate axons provide trophic support neurons cns dysfunction associated group disorders known demyelinating diseases multiple sclerosis oligodendrocytes derived oligodendrocyte precursor cells differentiate premyelinating oligodendrocytes eventually mature oligodendrocytes development function oligodendrocytes tightly regulated variety molecules including laminin major protein extracellular matrix accumulating evidence suggests laminin actively regulates every aspect oligodendrocyte biology including survival migration proliferation differentiation myelination can laminin exert diverse functions oligodendrocytes speculated distinct laminin isoforms laminin receptors key signaling molecules expressed oligodendrocytes different developmental stages reasons understanding molecular targets signaling pathways unique aspect oligodendrocyte biology will enable accurate manipulation oligodendrocyte development function may implications therapies demyelinating diseases review first introduce oligodendrocyte biology followed expression laminin laminin receptors oligodendrocytes cns cells next functions laminin oligodendrocyte biology including survival migration proliferation differentiation myelination discussed detail last key questions challenges field discussed providing comprehensive review laminins roles ol lineage cells hope stimulate novel hypotheses encourage new research fieldpmid34773273 doi101002 glia24117,1.0
populationbased incidence clinicoradiological characteristics tumefactive demyelination olmsted county minnesota usa eur j neurol 2021 nov 12 doi 101111 ene15182 online ahead printabstractbackground tumefactive demyelination td presents large inflammatory lesions mimicking tumors spaceoccupying lesions limited epidemiology clinical radiologic data exist report incidence rate clinical radiological features olmsted county minnesotamethods retrospectively reviewed patients cns inflammatory demyelinationrelated diagnostic codes 1 1 9812 31 18 via rochester epidemiology project database incidence rates age sex adjusted 2010 us total population used expanded disability status scale score edss assess outcomes index attack last followup results 15 792 multiple sclerosis ms patients 8 males 7 females tumefactive ms representing 19 ms population median attackonset age 342 years range 261 tumefactive lesion first clinical ms attack 8 16 patients csf oligoclonal bands ocbs present 8 12 patients 11 16 patients met barkhof criteria dissemination space remained fully ambulatory edss 4 13 16 81 median followup duration 105 years range 1205 ageadjusted annual incidence rates 046 100 000 95 ci 012081 females 066 100 000 95 ci 023102 males overall 056 100 000 95 ci 028083 age sexadjusted 2010 us total population overall annual incidence rate 057 95 ci 028084 despite aggressive clinical presentation disease onset patients remained fully ambulatory edss4 13 16 relapsingremitting courseconclusions although incidence rare td suspected patients presenting subacutely progressive neurological deficits associated mri findings ring enhancement adc restriction ocb spinal fluid analysispmid34773343 doi101111 ene15182,1.0
cognitive function oral health relapsingremitting multiple sclerosis clin oral investig 2021 nov 13 doi 101007 s00784021042721 online ahead printabstractobjectives multiple sclerosis ms often associated reduced cognitive function also emerging evidence heightened vulnerability oral health problems however although links cognitive function oral health identified special populations remains established whether relationship also evident people ms aim study provide first empirical test whether relationship cognitive function oral health people diagnosed relapsingremitting multiple sclerosis rrms methods one hundred eleven individuals evaluated 56 people diagnosed rrms 55 demographically matched healthy controls participants completed objective oral health assessment well standardized battery assessed six distinct neurocognitive domainsresults relative controls people rrms presented higher rates decayed teeth mild gingivitis also performed poorly three six neurocognitive domains assessed language complex attention executive function however rrms group associations emerged oral health performance six neurocognitive domainsconclusions data crossvalidate previous research shows people rrms likely present reduced cognitive function poorer oral health also extends literature meaningful way additionally showing first time clinical features unrelated rrmsclinical relevance findings emphasize need early assessment oral health cognitive function people rrms appropriate interventions support can put place clinical symptomspmid34773142 doi101007 s00784021042721,0.0
clinical application stem cell therapy neurogenic bladder systematic review metaanalysis int urogynecol j 2021 nov 12 doi 101007 s00192021049866 online ahead printabstractintroduction hypothesis review aims investigate effect stem cell sc therapy management neurogenic bladder ngb four neurological diseases including spinal cord injury sci parkinsons disease pd multiple sclerosis ms stroke clinical settingmethods electronic database search conducted cochrane library embase proquest clinicaltrialgov google scholar medline via pubmed ovid web science scopus ongoing trial registers conference proceedings june 2019 updated hand searching 1 february 2021 randomized controlled trials rcts quasi rcts phase ii clinical trials casecontrol retrospective cohorts comprehensive case series evaluated regenerative potential scs management ngb included cochrane appraisal risk bias checklist standardized critical appraisal instrument jbi metaanalysis statistics assessment review instrument jbimastari used appraise studiesresults twentysix studies among 1282 relevant publications met inclusion criteria sc therapy applied sci ms patients phase ii clinical trials without control arm conducted studies four rcts four studies 153 participants included metaanalysis main route transplantation via lumbar puncture serious adverse events nine studies sci one ms used urodynamics others reported improvement based patient satisfaction sc therapy significantly improve residual urine volume detrusor pressure maximum bladder capacity also quality publications low unclearconclusion although clinical trials provide evidence safety effectiveness mscs management ngb metaanalysis results show significant improvement however interpretation study results difficult lack placebo controlspmid34767058 doi101007 s00192021049866,0.0
mribased thalamic volumetry multiple sclerosis using fslfirst systematic assessment common error modes j neuroimaging 2021 nov 12 doi 101111 jon12947 online ahead printabstractbackground purpose fsls fmribs integrated registration segmentation tool fslfirst widely used wellvalidated tool automated thalamic segmentation common application important longitudinal measure multiple sclerosis ms however fslfirsts algorithm based shape models derived nonms groups present study sought systematically assess common thalamic segmentation errors made fslfirst mris people multiple sclerosis pwms methods fslfirst applied generate thalamic segmentation masks 890 mr images pwms images masks reviewed systematically classify quantify errors well associated anatomical variations mri abnormalities cases overt errors n 362 thalamic masks corrected quantitative volumetric differences calculatedresults entire quantitative volumetric group mean volumetric error fslfirst 274 0360 ml among corrected cases mean volumetric error 679 0894 ml average percent volumetric error associated seven error types two anatomical variants motions artifacts reported additional analyses showed presence motion artifacts anatomical variations significantly increased probability error 2 1814 p 01 2 6489 p 001 respectively finally thalamus volume error negatively associated degree atrophy smaller thalami systematically overestimated r 28 p 001 conclusions pwms fslfirst thalamic segmentation miscalculates thalamic volumetry predictable fashion may biased overestimate highly atrophic thalami recommended segmentations reviewed corrected manually appropriate specific studiespmid34767684 doi101111 jon12947,0.0
changes john cunningham virus index multiple sclerosis patients treated different diseasemodifying therapies curr neuropharmacol 2021 nov 11 doi 102174 1570159x19666211111123202 online ahead printabstractbackground progressive multifocal leukoencephalopathy pml opportunistic infection caused john cunningham virus jcv reactivation potentially associated natalizumab ntz treatment multiple sclerosis ms antijcv antibodies titre jcv index increases ntz treatment however effects disease modifying therapies dmts jcv index fully exploredobjective evaluate changes jcv index treatment several dmtsmethods longitudinal study evaluated jcv index starting dmt t0 dmt t1 results total 260 654 females mean age 43113 enrolled 68 262 treated fingolimod fty 65 25 rituximab ocrelizumab rtx ocr 37 142 dimethylfumarate dmf 29 112 cladribine cld 23 88 teriflunomide tfm 20 77 interferon glatiramer acetate ifn ga 18 69 alemtuzumab alm t1 percentage patients jcv index 090 significantly increased alm group 167 versus 667 p005 percentage patients jcv index 151 significantly reduced rtx ocr group 516 versus 375 p004 fty group significant reduction percentage patients jcv index 090 also found 235 versus 14 p00006 mean jcv index reduced rtx ocr alm groups significant increase observed fty groupconclusion dmts t b depleting mechanism action induced significant reduction jcv index results may suggest new possible sequencing strategies potentially maximizing disease control reducing pml riskpmid34766895 doi102174 1570159x19666211111123202,0.0
immersive virtual reality vestibular rehabilitation multiple sclerosis case report jmir serious games 2021 oct 12 doi 102196 31020 online ahead printabstractbackground background dizziness imbalance common disabling symptoms multiple sclerosis ms patients caused central peripheral mixed vestibulopathy central vestibular disorder frequent report ms population due demyelination vestibular rehabilitation ameliorates symptoms repercussions quality life however immersive virtual reality vri growing tool fieldwork previous research performed studying effects msobjective objective apply vri vestibular training protocol patient ms assess effects induced experimental interventionmethods methods case study 54yearold woman relapsing remitting multiple sclerosis rrms developed standardized vri exercise protocol vestibular rehabilitation based gold standard vestibular training cawthornecooksey 20session intervention formed 10 initial sessions 10 advanced sessions 50minute session will performed 23 times per week 7 weeks four evaluations carried study period baseline t0 two intervention phases t1 end intervention onemonth followup t3 outcomes research dizziness balance gait impact fatigue quality life repercussions muscular tone usability hmdresults results patient improved dhi t062 points t24 bbs t047 t254 itug t0835 sec t2557 sec muscular tone erector spinae rectus femoris soleus mfis t061 t237 msqol54 t2 physical area6716 t2 mental area 3356 receiving vri vestibular protocol system usability scale reached 90 usability gradeconclusions conclusions although research needed study provided initial evidence first vri vestibular protocol ms population improve dizziness balance gait impact fatigue quality life muscular tone exergame intervention study may help set standardized vri protocol vestibular rehabilitationclinicaltrial clinicaltrialsgov nct04497025pmid34766551 doi102196 31020,1.0
retinal intereye difference atrophy progression multiple sclerosis diagnostics j neurol neurosurg psychiatry 2021 nov 11jnnp2021327468 doi 101136 jnnp2021327468 online ahead printabstractbackground visual system included diagnostic criteria multiple sclerosis ms demonstrate dissemination space dis dissemination time dit objective investigate diagnostic value retinal asymmetry msmethods prospective longitudinal study individuals ms n151 healthy controls n27 optical coherence tomography oct performed 0 2 4 years macular ganglion cell inner plexiform layer mgcipl thickness determined well measures retinal asymmetry intereye percentage difference iepd intereye absolute difference iead receiver operator characteristics curves plotted area curve auc calculated group comparisons mgcipl iepd iead atrophy ratesresults diagnostic accuracy iepd iead differentiating bilateral unilateral ms optic neuritis high stable time aucs 088093 iepd slightly outperformed iead atrophy rates showed low discriminatory abilities differentiating ms controls auc 049058 conclusion intereye differences mgcipl value demonstration dis individuals longstanding ms dit may considered test detect dis future diagnostic criteria validation large prospective study people presenting symptoms suggestive ms requiredpmid34764152 doi101136 jnnp2021327468,0.0
characterizing internet search patterns neurologic neurosurgical conditions following celebrity diagnosis j neurosurg sci 2021 nov 11 doi 1023736 s0390561621055697 online ahead printabstractbackground social media internet platforms become significant drivers massinformation highly publicized events john mccains announcement glioblastoma diagnosis often drive national public interest medical topics improved understanding temporality interest spikes well nature information garners attention outside medical community can help inform ways medical community can boost awareness interest field neurosurgerymethods utilized explore topics feature google trends obtain web news youtube search data may 1 2015 may 1 2019 terms glioblastoma brain tumor stroke multiple sclerosis identify periods visibly increased search interestresults search results glioblastoma showed significantly elevated average interest period july 323 2017 compared generated since specific time period 426 vs 873 p0001 increased search activity therefore directly correlated john mccains public announcement glioblastoma diagnosis similar search interest spike evident using search term brain tumor 873 vs 642 p0001 search results multiple sclerosis showed result online buzz created selma blairs battle disease significantly elevated average interest october 8 2018 october 28 2018 february 11 2019 march 3 2019 compared average interest remaining time 59 vs 4016 p0001 69 vs 4016 p0001 finally corresponding elevations youtube search interest terms associated increased interest google trendsconclusions following major events related neurological disease public figures expected rise google search interest relevant topics findings suggest optimal window approximately 2 weeks following events activist clinical groups publicize desired message field neurosurgery neurological science increase public awareness regarding specific diseases regression baseline interest 4months following eventpmid34763394 doi1023736 s0390561621055697,0.0
selective capture antinglucosylated nthi adhesin peptide antibodies multivalent dextran conjugate chembiochem 2021 nov 11 doi 101002 cbic202100515 online ahead printabstracttentaclelike polymers decorated several copies peptide antigens can interesting tools increase ability capture circulating antibodies patient sera using cooperative effects stronger avidity previously showed antibodies multiple sclerosis ms patient sera preferentially recognize hyperglucosylated adhesin protein hmw1 nontypeable haemophilus influenzae nthi selected cterminal hmw1 13471354 minimal epitope prepared diglucosylated analogue ackan glc vtln glc ttgk n 3 nh 2 graft 40 kda dextran scaffold modified glycidylpropargyl moieties perform copper catalysed alkyneazide coupling reaction cuaac quantitative nmr measurements allowed characterize peptide loading 195 multivalent dextran conjugate novel polymeric structure displayed optimal capturing properties igg interestingly igm antibodies ms sera specific antibodies representative ms serum successfully depleted using sepharose resin bearing new glucosylated multivalent conjugate confirmed elisa results may offer promising proofofconcept selective purification high affinity autoantibodies sera patients affected autoimmune patients general specific high affinity antibodies minimal glycosylated epitope asn glc sera multiple sclerosis ms patients particularpmid34761861 doi101002 cbic202100515,0.0
histone deacetylase inhibitor belinostat ameliorates experimental autoimmune encephalomyelitis mice inhibiting tlr2#x2f myd88 hdac3#x2f nfb p65mediated neuroinflammation pharmacol res 2021 nov 7105969 doi 101016 jphrs2021105969 online ahead printabstractmultiple sclerosis ms th cellmediated inflammatory demyelinating autoimmune disease ms cured longterm drug treatment still needed ms patients study examined effect belinostat panhistone deacetylase inhibitor hdaci experimental autoimmune encephalomyelitis eae elucidated mechanism action found belinostat alleviates clinical symptoms histopathological central nervous system cns inflammation demyelination outcomes eae mice compared ms oral drug dimethyl fumarate dmf 100mg kg belinostat 30mg kg treatment exhibited better efficacy improving clinical symptoms eae mice belinostat treatment significantly suppressed activation m1 microglia proinflammatory cytokine expression effects m2 microglial polarization belinostat also decreased inos levels lpsstimulated bv2 microglia accordingly belinostat treatment eae mice significantly inhibited activation tlr2 myd88 signaling pathway downregulated expression hdac3 upregulating acetylated nfb p65 levels taken together data demonstrate first time belinostat ameliorates eae mice inhibiting neuroinflammation via suppressing m1 microglial polarization implicating belinostat potential candidate treatment multiple sclerosispmid34758400 doi101016 jphrs2021105969,1.0
effects orally administered cannabidiol neuroinflammation intestinal inflammation attenuation experimental autoimmune encephalomyelitis j neuroimmune pharmacol 2021 nov 10 doi 101007 s11481021100236 online ahead printabstractcannabidiol cbd bioactive compound isolated cannabis plants garnered attention within medical community due potent antiinflammatory properties better understand cbd limits excessive neuroinflammation administered cbd via oral gavage 20 mg kg murine model multiple sclerosis ms known experimental autoimmune encephalomyelitis eae using single cell rna sequencing scrna seq arraybased transcriptomics able delineate cbd limits excessive inflammation within central nervous system cns well within intestinal lining eae indepth scrna seq analysis cns tissue demonstrated cbd treatment resulted significant reduction cxcl9 cxcl10 il1 expression within cns leading inhibited infiltration inflammatory macrophages cbd inhibited il1 production independent classical cannabinoid receptors cb1 cb2 cbd treatment also led induction myeloidderived suppressor cells mdscs cns periphery interestingly cbd treatment eae mice revealed significant suppression inflammation gastrointestinal gi tract intestinal epithelial cells iecs cbd treated mice demonstrated transcriptional inhibition family pyroptosis initiators drive localized inflammation known gasdermins gsdms investigation gi tract via 16s sequencing cecal fecal contents demonstrated oral administration cbd resulted significant changes intestinal microbiota composition findings demonstrate beneficial effect cbd treatment autoimmune neuroinflammation ablating expression proinflammatory chemoattractants regulating inflammatory macrophage activity promoting mdsc expansion limiting systemic lowgrade inflammation gi tract culminating attenuation eaepmid34757526 doi101007 s11481021100236,0.0
novel probiotic strain exerts therapeutic effects mouse model multiple sclerosis altering expression inflammasome ido genes modulation t helper cytokine profile metab brain dis 2021 nov 10 doi 101007 s11011021008577 online ahead printabstractmultiple sclerosis inflammatory demyelinating disease commences neuronal cell destruction recently promising evidence synergic effects combined supplementation vitamin d probiotics modulating gut microbiota metabolome emerging bacillus coagulans ibrcm10791 novel strain chosen prevention treatment impacts regular administered studied cuprizoneinduced c57bl 6 mouse demyelination mice divided six groups received daily dose cuprizone probiotics investigate effect probiotic ido1 cyp27b1 nlrp1 nlrp3 aim2 expression estimated realtime pcr il4 il17 ifngamma tgfbeta cytokines measured elisa results showed significant decrease il17 ifn modulatory effects il4 tgf hand demonstrated significant decrease expression ido1 cyp27b1 nlrp1 nlrp3 aim2 genes prevention treatment groups compared cuprizone group also significant enhancement rate remyelination alternations proved lfb staining ymaze test conclusion study provides insight therapeutic effect chosen strain probiotic correlated modulation level inflammatory antiinflammatory cytokines demonstrated expression genes related tryptophan vitamin d inflammasome pathways affected bcoagulans study beneficial provide novel cotherapeutic strategy multiple sclerosispmid34757579 doi101007 s11011021008577,1.0
interventions promote independent participation among communitydwelling middleaged adults longterm physical disabilities systematic review disabil rehabil 2021 nov 10112 doi 101080 0963828820211998668 online ahead printabstractpurpose people aging longterm physical disabilities pawltpd aging accelerated rate beginning middleage face agerelated challenges conjunction existing disabilities thus maintaining independence age often difficult aim systematic review examine effectiveness rehabilitation interventions middleaged pawltpd participate independently home communitymaterials methods searched four databases medline cinahl web science embase studies published january 2005 december 2020 information included studies extracted using critical appraisal form studies categorized based common themes assigned level evidence assessed risk biasresults fourteen articles included common themes derived fall risk reduction functional capacity community mobility function within home strongest evidence supports wheelchair skills training programs wstps among manual wheelchair users targeted paretic limb exercise poststroke moderate evidence supports exercise multicomponent interventions multiple sclerosis adaptive strategy training wstps improve satisfaction mobility power wheelchair users home modifications assistive technology mobilityimpaired individualsconclusion interventions strong moderate evidence routinely offered middleaged pawltpd future research focus developing evidencebased interventions middleaged pawltpdimplications rehabilitationmiddleaged pawltpd face agingrelated challenges people without disabilities will experience additional difficulties due compounding effects longterm health conditions agingcurrent effective interventions promote participation middleaged pawltpd measured wide range outcomes many interventions used clinicians casebycase basiswheelchair skills training found strongest evidence recommended use middleaged pawltpd use manual power wheelchairspmid34757870 doi101080 0963828820211998668,0.0
vivo stiffness multiple sclerosis lesions similar normalappearing white matter acta biomater 2021 oct 28s17427061 21 006991 doi 101016 jactbio202110038 online ahead printabstractin 1868 french neurologist jeanmartin charcot coined term multiple sclerosis ms observation numerous white matter wm glial scars felt like sclerotic tissue nowadays magnetic resonance elastography mre can generate images contrast stiffness cs soft vivo tissues may therefore sensitive ms lesions provided sclerosis indeed mechanical signature disease analyzed cs total 147 lesions patients relapsingremitting ms compared control regions contralateral brain regions phantom data well performed numerical simulations determine delineation limits multifrequency mre 2040hz ms mre analysis simulated waves revealed delineation limit approximately 10 cs detecting 9mm lesions mean size patient population due inversion bias limit reached true cs 11 soft 35 stiff lesions vivo mre identified 35 stiffer lesions 17 softer lesions compared surrounding wm mean stiffness 93482pa however similar pattern found contralateral brain suggesting range stiffness changes wm lesions due ms within normal range wm variability normal heterogeneityrelated cs consequently charcots original intuition ms focal sclerotic disease can neither dismissed confirmed vivo mre however observation ms lesions markedly differ stiffness surrounding brain tissue suggests marked tissue sclerosis mechanical signature ms statement significance multiple sclerosis ms named jm charcot sclerotic changes brain tissue found postmortem autopsies since nothing revealed actual stiffening ms lesions vivo studying viscoelastic properties plaques natural environment major challenge can overcome mr elastography mre therefore used multifrequency mre answer question whether ms lesions patients relapsingremitting disease course mechanically different surrounding tissue findings suggest range stiffness changes white matter lesions due ms within normal range white matter variability vivo tissue sclerosis might mechanical signature mspmid34757062 doi101016 jactbio202110038,0.0
adultonset vanishing white matter patient eif2b3 variants misdiagnosed multiple sclerosis neurol sci 2021 nov 9 doi 101007 s10072021057104 online ahead printabstractbackground vanishing white matter vwm autosomal recessive disorder characterized childhood ataxia central hypomyelination adultonset vwm considered differential diagnosis suspected cases multiple sclerosis ms methods targeted region sequencing trs sanger sequencing validation performed identify validate likely pathogenic mutations family vwmresults main clinical manifestations proband included decreased vision sleepiness accompanied atrophy corpus callosum affected inner rim corpus callosum decreased apparent diffusion coefficient value persistent hyperintensitydiffusionweighted imaging atrophied optic nerve recordable visual evoked potentials due slow development atypical vwm image features ms initially suspected prednisone administered patients condition improve significantly diseases considered trs sanger sequencing identified compound heterozygous mutations eif2b3 proband c965c g pala322gly exon 8 c130g pglu44lys exon 2 missense mutations inherited mother father respectively probands oldest brother compound heterozygous mutations showed symptomsconclusion first report adultonset vwm chinese family initially ms suspected genetic testing confirmed diagnosis vwm study may broaden clinical spectrum eif2b3 thus providing foundation research pathogenesis genetic therapy vwmpmid34755279 doi101007 s10072021057104,1.0
abca8b promotes myelination via regulation chondroitin sulfate proteoglycan 4 localization oligodendrocyte precursor cells mice j lipid res 2021 nov 6100147 doi 101016 jjlr2021100147 online ahead printabstractthe myelin sheath wrapped around axons lipidenriched structure produced mature oligodendrocytes disruption myelin sheath observed several neurological diseases multiple sclerosis crucial component myelin sphingomyelin levels can increased abca8 member atpbinding cassette transporter family abca8 highly expressed cerebellum specifically oligodendroglia however whether abca8 plays role myelination mechanisms underlie role remain unknown found absence abca8b mouse ortholog abca8 led decreased numbers cerebellar oligodendrocyte precursor cells opcs mature oligodendrocytes mice show oligodendrocytes abca8 interacts chondroitin sulfate proteoglycan 4 cspg4 molecule essential opc proliferation migration myelination absence abca8b localization cspg4 plasma membrane decreased contributing reduced cerebellar cspg4 expression cerebellar cspg4+ opcs also diminished leading decreased mature myelinating oligodendrocyte numbers cerebellar myelination levels abca8b mice addition electron microscopy analyses showed number nonmyelinated cerebellar axons increased cerebellar myelin thickness gratio myelin sheath periodicity axonal diameter decreased indicative disordered myelin ultrastructure line disrupted cerebellar myelination abca8b mice showed lower cerebellar conduction velocity disturbed locomotion summary abca8 modulates cerebellar myelination part functional regulation abca8interacting protein cspg4 findings suggest abca8 disruption may contribute pathophysiology myelin disorderspmid34752805 doi101016 jjlr2021100147,1.0
t1#x2f t2 ratio quantitative sensitive marker brain tissue integrity multiple sclerosis j neuroimaging 2021 nov 9 doi 101111 jon12943 online ahead printabstractbackground purpose aim study determine whether cerebral white matter wm microstructural damage defined decreased fractional anisotropy fa increased axial ad radial rd diffusivities detected accurately measuring t1 t2 ratio relapsingremitting multiple sclerosis rrms patients compared healthy control hc subjectsmethods twentyeight rrms patients 24 hc subjects included study regionbased analysis based icbm81 diffusion tensor imaging dti atlas wm labels performed compare t1 t2 ratio dti values normalappearing wm nawm regions interest lesions segmentation also performed compared hc global wmresults significant 1965 decrease t1 t2 ratio values observed nawm regions rrms patients compared hc significant 630 decrease fa well significant 476 1027 increases ad rd respectively observed rrms compared hc group various nawm regions compared global wm hc mask lesions significantly decreased t1 t2 ratio fa increased ad rd p 001 conclusions results showed significant differences rrms hc dti t1 t2 ratio measurements t1 t2 ratio even demonstrated extensive wm abnormalities compared dti thereby highlighting ratios sensitivity subtle differences cerebral wm structural integrity using conventional mri sequencespmid34752685 doi101111 jon12943,0.0
diffusely abnormal white matter multiple sclerosis j neuroimaging 2021 nov 9 doi 101111 jon12945 online ahead printabstractmri enables detailed vivo depiction multiple sclerosis ms pathology localized areas ms damage commonly referred lesions plaques focus clinical research mri studies four decades nonplaque mri abnormality present least 25 ms patients received far less attention diffusely abnormal white matter dawm dawm poorly defined boundaries signal intensity normalappearing white matter classic lesions proton density t2 weighted images clinical phenotypes ms demonstrate dawm including clinically isolated syndrome dawm associated higher lesion volume reduced brain volume earlier conversion ms advanced mri metric abnormalities dawm tend greater nawm severe focal lesions myelin axons waterrelated changes commonly reported histological studies demonstrate primary lipid abnormality dawm axonal damage lesser involvement myelin proteins review provides overview dawm identification summarizes vivo postmortem observations comments potential pathophysiological mechanisms may underlie dawm ms given prevalence potential clinical impact dawm number imaging studies focusing dawm insufficient characterization dawm significance microstructure benefit larger longitudinal additional quantitative imaging efforts revisiting data previous studies included proton density t2 imaging enable retrospective dawm identification analysispmid34752664 doi101111 jon12945,1.0
retinal imaging biomarkers neurodegenerative diseases clin exp optom 2021 nov 9111 doi 101080 0816462220211984179 online ahead printabstractthe timely detection neurodegenerative diseases central improving clinical care well enabling development deployment diseasemodifying therapies retinal imaging emerging method detect features number neurodegenerative diseases given anatomical functional similarities retina brain review provides overview current status retinal imaging biomarkers neurodegenerative diseases including alzheimers disease parkinsons disease lewy body dementia frontotemporal dementia huntingtons disease multiple sclerosis whilst research findings promising efforts harmonise study designs imaging methods will important translating findings clinical care may mean eye care providers will play important roles detection variety neurodegenerative diseases futurepmid34751086 doi101080 0816462220211984179,0.0
direct indirect neurological signs covid19 neurosci behav physiol 2021 nov 4111 doi 101007 s11055021011449 online ahead printabstractobjective systematize neurological manifestations covid19 materials methods systematic computerized analysis currently available publications neurological manifestations covid19 undertaken 2374 reports pubmed topological data analysis results set interactions infection sarscov2 metabolic impairments affecting neurotransmitters acetylcholine dopamine serotonin gaba enkephalins neurotrophins micronutrients chronic acute inflammation encephalopathy cerebral ischemia neurodegeneration including demyelination described typical neurological manifestations covid19 anosmia ageusia due ischemia neurodegeneration systematic increases proinflammatory cytokine levels covid19 provoked ischemic stroke guillainbarr syndrome polyneuropathy encephalitis meningitis parkinsonism coronavirus infection increased severity multiple sclerosis myopathies possible roles human virome pathophysiology covid19 considered clinical case patient neurological complications covid19 described conclusions longterm perspective covid19 promotes increases neurodegenerative changes requires special neurological rehabilitation programs use cholinergic drugs antihypoxic agents compatible covid19 therapy advisedpmid34751196 pmcpmc8566113 doi101007 s11055021011449,1.0
antifibrotic factor klf4 repressed mir10#x2f tfap2a#x2f tbx5 axis dermal fibroblasts insights twins discordant systemic sclerosis ann rheum dis 2021 nov 8annrheumdis2021221050 doi 101136 annrheumdis2021221050 online ahead printabstractobjectives systemic sclerosis ssc complex disease unknown aetiology inflammation fibrosis lead multiple organ damage currently effective therapy can halt progression fibrosis reverse thus studies provide novel insights disease pathogenesis identify novel potential therapeutic targets critically neededmethods used global gene expression genomewide dna methylation analyses dermal fibroblasts dfbs unique cohort twins discordant ssc identify molecular features pathology validated findings using vitro ex vivo vivo modelsresults results revealed distinct differentially expressed methylated genes including several transcription factors involved stem cell differentiation developmental programmes klf4 tbx5 tfap2a homeobox genes micrornas mir10a mir10b target several deregulated genes show klf4 expression reduced ssc dfbs expression repressed tbx5 tfap2a also show klf4 antifibrotic conditional knockout fibroblasts promotes fibrotic phenotypeconclusions data support role epigenetic dysregulation mediating ssc susceptibility dfbs illustrating intricate interplay cpg methylation mirnas transcription factors ssc pathogenesis highlighting potential future use epigenetic modifiers therapiespmid34750102 doi101136 annrheumdis2021221050,0.0
exploiting preferential phagocytic uptake nanoparticleantigen conjugates effective treatment autoimmunity nanomedicine 2021 nov 5102481 doi 101016 jnano2021102481 online ahead printabstracttolerance induction central suppression autoimmunity engineered preferential uptake nanoconjugated autoantigens spleenresident macrophages reintroduce selftolerance suppress autoimmunity brain autoantigen myelin oligodendrocyte glycoprotein mog conjugated 200 500nm silica nanoparticles snp delivered spleen liverresident macrophages experimental autoimmune encephalomyelitis eae mice model multiple sclerosis mogsnp conjugates significantly reduced signs eae low dose 50g compared higher dose 800g freemog associated reduced proliferation splenocytes proinflammatory cytokines secretion decreased spinal cord inflammation demyelination axonal damage notably biodegradable porous snp showed enhanced disease suppression assisted elevated levels regulatory t cells programmeddeath ligands pdl1 2 splenic lymph node cells results demonstrate targeting nanoconjugated autoantigens tissueresident macrophages lymphoid organs can effectively suppress autoimmunitypmid34748963 doi101016 jnano2021102481,1.0
glia major player glutamategaba dysregulationmediated neurodegeneration j neurosci res 2021 nov 8 doi 101002 jnr24977 online ahead printabstractthe imbalance glutamate aminobutyric acid gaba results loss synaptic strength leading neurodegeneration dogma field considered neurons main players excitationinhibition e balance however current strategies focusing neurons failed completely understand condition bringing importance glia alternative modulator neuroinflammation glia alter activity neurons source neurotrophic neurotoxic factors reviews primary goal illustrate role glia e balance central nervous system interaction neurons rather focusing neuronal targets take deeper look glial receptors proteins also explored drug targets early responders neurotoxic insults review summarizes neuronglia interaction concerning gaba glutamate possible targets involvement e imbalance neurodegenerative diseases like alzheimers disease parkinsons disease huntingtons disease multiple sclerosispmid34748682 doi101002 jnr24977,0.0
insight role liposomal therapeutics reversion multiple sclerosis expert opin drug deliv 2021 nov 8 doi 101080 1742524720212003327 online ahead printabstractintroduction multiple sclerosis ms autoimmune disease complicated immunopathology makes management relevant various factors novel pharmaceutical vehicles especially liposomes can support efficacious handling disease early detection prognosis also therapeutic manner wellknown trigger ms onset predominance cellular humoral immunity enhancement inflammatory cytokines level installation liposomes nanoparticles control disease holds great promise nowareas covered various types liposomes different properties purposes formulated targeted immune cells surface manipulations may encapsulated antiinflammatory msrelated therapeutics immunodominant myelinspecific peptides attaining higher therapeutic efficacy drugs tolerance induction cationic liposomes also highly applicable gene delivery antiinflammatory cytokines silencing inflammatory cytokines liposomes also used biotools comprehending ms pathomechanisms diagnostic agentsexpert opinion efforts manage ms nanomedicine especially liposomal therapeutics pave new avenue highthroughput medication autoimmune disease translation clinic future overcoming challenges ms patients confrontpmid34747298 doi101080 1742524720212003327,1.0
restingstate functional brain connectivity human mentalizing biobehavioral mechanisms theory mind multiple sclerosis soc cogn affect neurosci 2021 nov 8nsab120 doi 101093 scan nsab120 online ahead printabstractalthough neural hubs mentalizing acknowledged brain mechanisms underlying mentalizing deficit characterizing different neurological conditions still matter debate investigate neural underpinning theory mind tom deficit multiple sclerosis ms region interest roi based restingstate fmri study proposed 37 ms patients 23 females mean age54081137 years median expanded disability status scale600 underwent mri neuropsychosocial examination compared 20 sexageeducation matched healthy subjects neuroanatomical tom model constructed deriving 11 bilateral roi withinfunctional connectivity fc assessed test group differences correlation psychosocial scores also investigated lower tom performance registered ms cognitive affective tom significantly associated processing speed disconnection limbicparalimbic network prefrontal execution loops observed trend aberrant intrinsic connectivity ms within anterior cingulate cortex acc also reported finally correlation cognitive tom intrinsic fc detected acc dorsal striatum belonging limbicparalimbic network likely explaining behavioral deficit ms results suggest aberrant intrinsic extrinsic connectivity constitutes crucial neural mechanism underlying tom deficit mspmid34748015 doi101093 scan nsab120,0.0
efficacy safety ocrelizumab patients relapsingremitting multiple sclerosis suboptimal response prior diseasemodifying therapies primary analysis phase 3b casting singlearm openlabel trial eur j neurol 2021 nov 8 doi 101111 ene15171 online ahead printabstractbackground using treatment goal evidence disease activity neda incorporating mri rebaselining assessed efficacy ocrelizumab patients relapsingremitting multiple sclerosis prior suboptimal response defined mri relapse criteria one two diseasemodifying therapies dmts methods casting prospective international multicenter singlearm openlabel phase iii trial nct02861014 patients expanded disability status scale edss score 40 discontinued prior dmt 6 months duration due suboptimal disease control received intravenous ocrelizumab 600 mg every 24 weeks 96 weeks primary endpoint neda defined absence relapses disability progression inflammatory mri measures prespecified mri rebaselining week 8 96 weeksresults total 680 patients enrolled 167 246 based mri activity week 96 748 95 ci 713780 n n492 658 patients neda neda highest among patients enrolled due mri activity alone 806 686896 n n50 62 versus relapse 751 690806 n n172 229 relapse mri 705 600790 n n74 105 neda across subgroups highest patients baseline edss score 25 772 728812 n n315 408 neda higher patients receiving one prior dmt 776 732816 n n312 402 versus two 703 643758 n n180 256 conclusions patients switching therapy due suboptimal disease control treatment ocrelizumab led overall high neda rate across wide range diseaserelated demographic subgroups regardless prior treatment background new safety signals detectedpmid34748672 doi101111 ene15171,0.0
alemtuzumab induced red cell aplasia immune cytopenias #39 pure#39 immunotherapy 2021 nov 8 doi 102217 imt20210163 online ahead printabstractwe report presentation outcome 28yearold female developed red cell aplasia following alemtuzumab therapy relapsing remitting multiple sclerosis patient also developed synchronous immune thrombocytopenia immune neutropenia aplastic anemia patient received high dose steroids intravenous immunoglobulin ivig rituximab red cell transfusions vincristine gcsf cyclosporin mycophenolate treat combination cytopenias period 6 months subsequent improvement bone marrow function alemtuzumab several recognized autoimmune complications little known potential hematological side effects combination red cell aplasia immune thrombocytic purpura autoimmune neutropenia previously described literature following alemtuzumab immunotherapy highlights importance monthly blood monitoring post alemtuzumab administrationpmid34743591 doi102217 imt20210163,0.0
vaccination setting patients autoimmune diseases times severe acute respiratory syndrome coronavirus type 2 pandemic using example multiple sclerosis patients longitudinal multicenter study eur neurol 2021 nov 518 doi 101159 000519582 online ahead printabstractbackground severe acute respiratory syndrome coronavirus type 2 sarscov2 infection represents serious health risk especially chronically ill people multiple sclerosis ms common chronic immunemediated neurological disease vaccinations play important role therapeutic ms management study aimed determining ms patients attitudes toward vaccinations governmental measures sarscov2 pandemic including associations sociodemographic clinical variablesmethods longitudinal multicenter study 200 ms patients investigated regarding vaccination attitudes first wave sarscov2 pandemic data vaccination status burden physical psychological social experienced caused pandemic related governmental safety measures registeredresults patients progressive ms felt significantly pandemicburdened patients relapsingonset ms p 0001 older patients frequently willing get vaccinated sarscov2 younger patients p 0001 first pandemic wave patients prepandemic willingness comply vaccination recommendations likely accept recommended standard vaccinations 60 vs 36 possible sarscov2 vaccination prepandemic nonwilling patients 667 vs 420 conclusions vaccination topic immediately present many patients pandemic ms patients need comprehensive understandable education meeting concerns using evidencebased convincing arguments subject vaccination particularly younger patients older patients already often willing become vaccinated complete vaccination status necessary avoid multiple infectionspmid34743082 doi101159 000519582,0.0
pleiotropic predisposition alzheimer#39 s disease educational attainment insights summary statistics analysis geroscience 2021 nov 6 doi 101007 s11357021004841 online ahead printabstractepidemiological studies report beneficial associations higher educational attainment edu alzheimers disease ad prior genomewide association studies gwas also reported variants associated ad edu separately analysis pleiotropic associations phenotypes may shed light edurelated protection ad performed pleiotropic metaanalyses using fishers method omnibus test applied summary statistics single nucleotide polymorphisms snps associated ad edu largescale univariate gwas suggestiveeffect 5 108 p 01 genomewide p 5 108 significance levels report 53 snps attained p 5 108 least one pleiotropic metaanalyses reported univariate gwas 5 108 p 01 46 pleiotropic snps according fishers method additionally fishers method identified 25 206 snps pleiotropic effects attained p 5 108 univariate gwas showed large fraction pleiotropic associations affected counterintuitive phenomenon antagonistic genetic heterogeneity explains increase rather decrease significance pleiotropic associations omnibus test functional enrichment analysis showed apart cancers gene set harboring nonpleiotropic snps characterized lateonset ad neurodevelopmental disorders pleiotropic gene set characterized broad spectrum progressive neurological neuromuscular diseases immunemediated conditions including progressive motor neuropathy multiple sclerosis parkinsons disease severe ad results suggest disentangling genes harboring variants without pleiotropic associations ad edu promising dissecting heterogeneity biological mechanisms adpmid34743297 doi101007 s11357021004841,0.0
impact covid19 pandemic international rehabilitation study ms cogex experience j neurol 2021 nov 5 doi 101007 s00415021108813 online ahead printabstractpandemic restrictions led changes therapy plans disrupted rehabilitation services people multiple sclerosis cogex international multicentre ms dualintervention cognitive rehabilitation aerobic exercise randomized controlled rehabilitation trial confined people progressive disease primary outcome cognition processing speed 11 treatment sites six countries participants required make 27 site visits 12 weeks collectively large inperson demands trial varying international policies containment covid19 might disproportionately impact administration cogex first lockdown centres closed average 829 sd 243 days one site required lockdown two occasions one site remained closed 16 months ten staff 192 required quarantine eight staff 154 tested positive covid 10 264 38 participants acquired covid19 survived mean duration enrollment delay 2367 sd 2145 days restarting participants whose interventions interrupted pandemic meant recalculating intervention prescriptions individuals impact pandemic cogex considerable study sites open participants staff shown considerable flexibility resilience keeping complex international endeavour running future general remains uncertain midst pandemic cautious optimism study will completed sufficient sample size robustly evaluate hypothesis provide meaningful results ms community impact interventions people progressive mstrial registration trial registered september 20th 2018 wwwclinicaltrialsgov identifier nct03679468 registration performed recruitment initiatedpmid34741240 doi101007 s00415021108813,0.0
epilepsy management tuberous sclerosis complex existing evolving therapies future considerations pediatr neurol 2021 sep 30 1261119 doi 101016 jpediatrneurol202109017 online ahead printabstracttuberous sclerosis complex tsc rare autosomal dominant condition affects multiple body systems disruption mammalian target rapamycin mtor pathway results abnormal cell growth proliferation protein synthesis cell differentiation migration tsc central nervous system mtor disruption also believed influence neuronal excitability promote epileptogenesis epilepsy common neurological manifestation tsc affects 80 90 individuals high rates treatment resistance 75 onset epilepsy majority individuals tsc occurs age two years critical time neurodevelopment medically refractory epilepsy earlyonset epilepsy associated intellectual disability tsc seizure control remission associated lower rates cognitive impairment current knowledge treatment epilepsy tsc expanded immensely last decade several new therapies preemptive vigabatrin therapy infants cannabidiol mtor inhibitors emerged recent years treatment epilepsy tsc review will provide clinicians comprehensive overview pharmacological nonpharmacological therapies available treatment epilepsy related tscpmid34740132 doi101016 jpediatrneurol202109017,0.0
validity reliability physical activity measures multiple sclerosis physiother theory pract 2021 nov 5117 doi 101080 0959398520211996498 online ahead printabstractpurpose purpose evaluate psychometric properties physical activity measures persons multiple sclerosis pwms methods adults multiple sclerosis recruited n 30 validation n 57 testretest steps measured piezorx yamax sw200 actigraph gt9x link aglink time different positions measured aglink validated data video analysis psychometric properties physical activity disability survey revised swedish version padsr sw evaluatedresults valid measures aglink using lowfrequency extension filter piezorx median absolute percentage errors meapes 0931 1333 meapes higher yamax sw200 29210 aglink display 36448 aglink normal filter 89489 indicating low validity aglink valid measurements sitting meape 120125 lying meape 310417 correlation padsr sw aglink steps r 0492 p 009 relative reliability padsr sw icc2 1 085 ci 076091 absolute reliability sem 054conclusion aglink piezorx valid measures steps pwms questionnaire padsr sw valid high relative reliability absolute reliability unsatisfactorypmid34738486 doi101080 0959398520211996498,0.0
correction rim lesions demonstrated early relapsingremitting multiple sclerosis using 3 tbased susceptibilityweighted imaging multiinstitutional setting neuroradiology 2021 nov 5 doi 101007 s00234021028442 online ahead printno abstractpmid34738181 doi101007 s00234021028442,0.0
case report recurrent severe uveitis secondary primary progressive multiple sclerosis responsive ocrelizumab ocul immunol inflamm 2021 nov 413 doi 101080 0927394820211980809 online ahead printabstractpurpose report case severe recurrent bilateral panuveitis secondary primary progressive multiple sclerosis responsive ocrelizumab infusionsobservation describe clinical progression 40 year old female presented 3week history insidious bilateral visual loss clinically consistent panuveitis diagnosis multiple sclerosis established serial magnetic resonance imaging mri coincided focal neurological events separated time initially good response high dose oral prednisolone however patient recurrent uveitis time dose weaned guidance neurology initiated treatment ocrelizumab stability ocular inflammation past 24 monthsconclusion sixmonthly 600mg ocrelizumab infusions may effective steroid sparing option patients severe recurrent bilateral panuveitis secondary primary progressive multiple sclerosispmid34735301 doi101080 0927394820211980809,0.0
effect air pollution covid19 severity sample patients multiple sclerosis eur j neurol 2021 nov 4 doi 101111 ene15167 online ahead printabstractbackground studies shown air pollution often assessed thin particular matter diameter 25 g m3 pm25 may contribute severe covid19 courses well plays role onset evolution multiple sclerosis ms however impact air pollution covid19 never explored specifically among patients ms pwms objectives retrospective observational study aims explore associations pm25 covid19 severity among pwmsmethods data retrieved italian webbased platform musc19 includes pwms covid19 pm25 20162018 average concentrations provided copernicus atmospheric monitoring service included italian patients inserted platform january 15 2020 april 9 2021 covid19 positive test used ordered logistic regression models study associations pm25 covid19 severityresults included 1087 patients 13 required hospitalization 2 admitted intensive care unit died based multivariate analysis higher concentrations pm25 increased risk worst covid19 course or190 p0009 conclusions even several factors explain unfavorable course covid19 pwms role air pollutants must considered investigatedpmid34735749 doi101111 ene15167,0.0
dentatenucleus gadolinium deposition magnetic resonance imaging ultrasonographic clinical correlates multiple sclerosis patients neurol sci 2021 nov 4 doi 101007 s10072021057024 online ahead printabstractobjective objective study find whether gadolinium accumulation dentate nucleus dn repeated gadoliniumbased contrast agent gbca administration multiple sclerosis ms patients related tissue alteration detectable transcranial ultrasoundmethods casecontrol study 34 patients 17 17 age sex ms severity durationmatched participants without visually rated dn t1hyperintensity received 228 mean 11 7 consecutive 15tesla mri examinations application linear gbca included realtime mriultrasound fusion imaging applied exactly superimposing dn identified mri calculate corresponding echointensity digitized ultrasound image analysis addition cerebellar ataxia cognitive performance assessed correlation analyses adjusted age ms duration ms severity time mri scansresults dntopons t1signal intensityratios dpsir larger patients visually rated dn t1hyperintensity compared without 116 010 vs 109 006 p 001 combined group dpsir correlated cumulative lineargbca dose r 049 p 0003 dpsir change last versus first mri r 059 p 0003 neither dpsir globus pallidus internustothalamus t1signal intensityratios related echointensity corresponding rois dpsir correlated dysarthria r 057 p 0001 subscore international cooperative ataxia rating scale clinical scoreconclusions dn gadolinium accumulation associated trace metal accumulation calcification tissue alteration detectable ultrasound possible mild effect dn gadolinium accumulation cerebellar speech function ms patients suggested present data needs validated larger study samplespmid34735650 doi101007 s10072021057024,0.0
mechanismbased criteria improve therapeutic outcomes progressive multiple sclerosis nat rev neurol 2021 nov 3 doi 101038 s4158202100581x online ahead printabstractin contrast multiple diseasemodifying therapies available relapsingremitting multiple sclerosis ms therapeutic options progressive ms pms limited recent advances understanding neuroimmunology pms including mechanisms drive slowly expanding lesions fuelled optimism improved treatment condition review highlight commonly observed neuropathology pms discuss associated mechanisms cns injury apply knowledge formulate criteria therapeutic efficacy pms beginning need early treatment owing substantial neuropathology already present initial clinical presentation requirements include antagonism neuroaxonal injury mediators proinflammatory microglia lymphocytes remediation oxidative stress resulting iron deposition mitochondrial dysfunction promotion neuroprotection remyelination consider whether current diseasemodifying therapies relapsingremitting ms meet criteria successful therapeutics pms suggest evidence favours early introduction sphingosine 1phosphate receptor modulators finally weigh emerging medications including repurposed generic medications brutons tyrosine kinase inhibitors fundamental criteria new therapeutic era pms success depends collectively understanding disease mechanisms drug characteristics including brain penetration rational usepmid34732831 doi101038 s4158202100581x,1.0
discovery preclinical characterization biib091 reversible selective btk inhibitor treatment multiple sclerosis j med chem 2021 nov 4 doi 101021 acsjmedchem1c00926 online ahead printabstractmultiple sclerosis chronic autoimmune neurodegenerative disorder central nervous system cns characterized inflammation demyelination axonal injury leading permeant disability early stage ms inflammation primary driver disease progression remains unmet need develop high efficacy therapies superior safety profiles prevent inflammation processes leading disability herein describe discovery biib091 structurally distinct orthosteric atp competitive reversible inhibitor binds btk protein dfgin confirmation designed sequester tyr551 important phosphorylation site btk inactive conformation excellent affinity preclinical studies demonstrated bib091 high potency molecule good druglike properties safety tolerability profile suitable clinical development highly selective reversible btki treating autoimmune diseases mspmid34734694 doi101021 acsjmedchem1c00926,1.0
review available data efficacy effectiveness nabiximols oromucosal spray sativex multiple sclerosis patients moderate severe spasticity background sativex usan nabiximols oromucosal spray indicated treatment multiple sclerosis ms patients moderate severe spasticity inadequate response antispasticity medications demonstrate clinically significant improvement initial trial therapy narrative review investigated efficacy effectiveness nabiximols oromucosal spray moderate severe ms spasticity examining spasticity 010 numerical rating scale nrs data interventional observational studies featured 4week trial period per european union approved labelsummary across study types clinically relevant statistically significant reductions mean ms spasticity 010 nrs scores measured soon treatment start maintained mid long term treatment responders initial responder rates 20 nrs improvement baseline week 4 ranged 476 814 tending lower randomized clinical trials setting clinically relevant responder rates 30 nrs improvement baseline week 12 similar study types range 3041 except one outlier 74 observational study two open studies reported treatment continuation 18 months approximately half patients initiated treatment longerterm studies symptomatic improvement ms spasticity maintained mean daily dosages 67 sprays day safety consistent known profile nabiximols key messages experimental observational studies nabiximols oromucosal spray recorded similar findings half twothirds ms patients begin treatment will perceive initial symptomatic relief spasticity within 4week trial period 40 patients initiate treatment will reach 30 nrs improvement threshold 3 months comprising majority patients continue longterm treatment trial therapy nabiximols useful identify patients likely gain longerterm improvement spasticity symptoms discontinue insufficient benefit,1.0
practicerelevant autoimmune diseases central nervous system pediatrics early diagnosis adequate initiation treatment nervenarzt 2021 nov 3 doi 101007 s0011502101211z online ahead printabstractbackground pediatric autoimmune diseases affecting central nervous system recently come focus attention important advances made field children multiple sclerosis ms led better understanding clinical characteristics treatment options furthermore new autoantibodies target antigens neurons peripheral nerves myelin sheath detectedobjective article summarizes new advances children ms addresses differences adult counterparts addition important forms autoimmune encephalitis nmethyl daspartate receptor nmdar myelin oligodendrocyte glycoprotein mog encephalitis children described together diagnostic algorithm therapeutic approach event suspected autoimmune encephalitis lastly clinical spectrum mog antibodyassociated diseases mogad detailedpmid34731279 doi101007 s0011502101211z,1.0
tumefactive demyelinating cns lesion a60yearold woman familial mediterranean fever wien med wochenschr 2021 nov 3 doi 101007 s1035402100893z online ahead printabstractwe report 60yearold woman familial mediterranean fever fmf developed cognitive impairment 16 years initial diagnosis mri new extensive white matter lesion right frontal lobe mild local mass effect without contrast enhancement detectable classified tumefactive lesion additional mr spectroscopy showed markedly increased choline levels accompanied significant lactate peak highly suggestive lowflorid demyelinating process although diffuse central nervous system cns lesions described single fmf cases tumefactive lesions observed fmf patients without concomitant multiple sclerosis summary case highlights rare differential diagnoses atypical inflammatory cns lesions clinical utility mr spectroscopypmid34731365 doi101007 s1035402100893z,1.0
setting meaningful goals rehabilitation qualitative study experiences clients clinicians working practical tool clin rehabil 2021 nov 32692155211046463 doi 101177 02692155211046463 online ahead printabstractobjective evaluate experience clients clinicians working tool help set goals personally meaningful rehabilitation clientsdesign applied tool outpatient rehabilitation setting clients clinicians experiences working tool evaluated individual semistructured interviews focus group interviews respectively thematic analysis used analyze datasetting university medical center rehabilitation centersubjects clients firsttime stroke n 8 multiple sclerosis n 10 clinicians n 38 intervention tool help set meaningful goals consisted session explore clients fundamental beliefs goals attitudes ii identify meaningful overall rehabilitation goal results session used multidisciplinary rehabilitation team iii help client set specific rehabilitation goals served achieve meaningful overall rehabilitation goalresults clients clinicians reported tool helped set meaningful overall rehabilitation goal specific goals became meaningful served achieve overall goal contributed clients intrinsic rehabilitation motivation clients meaningfulness rehabilitation goals facilitated process behavior change clients clinicians made suggestions tool improvedconclusion opinion clients clinicians tool indeed result goal setting personally meaningful development implementation evaluation tool warrantedpmid34730459 doi101177 02692155211046463,0.0
antipolymyositis#x2f scl antibodypositive overlap syndrome diffuse cutaneous systemic sclerosis dermatomyositis systemic lupus erythematosus antiphospholipid syndrome j dermatol 2021 nov 3 doi 101111 1346813816219 online ahead printabstracta 37yearold japanese man 3year history diffuse cutaneous systemic sclerosis admitted hospital high fever arthralgia myalgia muscle weakness physical examination revealed facial erythema gottrons sign mechanics hands addition skin sclerosis laboratory data revealed significantly elevated levels creatine kinase decreased complement antirnp antismith antidna anti2 glycoprotein 1 antipolymyositis pm scl75 antipm scl100 antibodies detected also urinary protein interstitial lung disease pericarditis multifocal cerebral infarctions leukoencephalopathy thus diagnosis overlap syndrome diffuse cutaneous systemic sclerosis dermatomyositis systemic lupus erythematosus antiphospholipid syndrome made intractable course treated multiple immunosuppressive immunomodulatory drugs including three rounds 1000 mg methylprednisolone pulse therapy first case report antipm scl antibodypositive overlap syndrome three major connective tissue diseasespmid34730249 doi101111 1346813816219,0.0
differences cardiometabolic comorbidities black white persons living multiple sclerosis arch phys med rehabil 2021 oct 30s00039993 21 015215 doi 101016 japmr202110011 online ahead printabstractobjective determine differences obesity type 2 diabetes hypertension black patients compared white patients multiple sclerosis ms design crosssectional database reviewsetting large academic medical center research records databaseparticipants 3 191 patient cases 77 female 34 black identified ms diagnosis within medical recordinterventions applicable main outcome measures diagnosis codes type 2 diabetes hypertension body mass index bmi race age sex collected anova continuous variables x2 analyses categorical variables conducted determine differences obesity diabetes hypertension race sex logistic regression conducted determine odds ratios developing diabetes hypertension based race sex bmi ageresults black patients twice likely diagnosed diabetes 215 95 ci 170 272 p00001 hypertension 244 95 ci 205 291 p00001 compared whites sex present greater likelihood diagnosed diabetes however males 122 times likely diagnosed hypertension compared females 95 ci 101 149 p00439 increased age bmi also significantly associated likelihood diagnosis diabetes hypertension age diabetes 105 95 ci 104 106 p00001 hypertension 106 95 ci 105 106 p00001 bmi diabetes obese vs normal 211 95 ci 143 311 p 00002 hypertension obese vs normal 172 95 ci 139 213 p 00001 conclusion black patients ms significantly likely cardiometabolic conditions white patients conditions associated poorer health outcomes people ms may impact differences ms disease course reported black patientspmid34728190 doi101016 japmr202110011,0.0
sex differences regulate immune responses experimental autoimmune encephalomyelitis multiple sclerosis eur j immunol 2021 nov 2 doi 101002 eji202149589 online ahead printabstractmultiple sclerosis ms autoimmune disease central nervous system cns afflicts 25 million people worldwide striking sex differences susceptibility progression disease humans females twice likely develop ms males whereas disease progression disability rapid males compared females however latter still controversial growing evidence mainly animal models innate adaptive immune responses different males females can influence outcome range diseases including infection cancer autoimmunity since ms immunemediated disease sex differences pathogenic immune responses may account differences susceptibility progression seen men versus women indeed data mouse model ms experimental autoimmune encephalomyelitis eae already provided evidence female mice earlier disease onset associated stronger th17 responses review will discuss possible immunological basis sex differences susceptibility disease outcome eae ms better understanding sex differences responses diseasemodifying therapies may lead improved patient treatment article protected copyright rights reservedpmid34727577 doi101002 eji202149589,0.0
correction disability assessment using google maps neurol sci 2021 nov 2 doi 101007 s1007202105707z online ahead printno abstractpmid34727256 doi101007 s1007202105707z,0.0
application step beat alignment approaches effect gait progressive multiple sclerosis severe cerebellar ataxia proof concept case study mult scler 2021 nov 213524585211054000 doi 101177 13524585211054000 online ahead printabstractbackground case report progressive multiple sclerosis cerebellar impairments reported synchronisation steps beats possible 12 usual walking cadence 1 minute walkingobjectives methods investigate effect synchronisation using two different alignment approaches patients gait pattern 2 minutes walking compared walking silenceresults conclusion proof concept showed adaptive approach successful resulting improved gait pattern compared conditions providing preliminary evidence support fullscale intervention studypmid34726562 doi101177 13524585211054000,0.0
efficacy transcranial direct current stimulation people multiple sclerosis comprehensive review eur j neurol 2021 nov 1 doi 101111 ene15163 online ahead printabstractbackground multiple sclerosis ms chronic inflammatory disease causing wide range symptoms including motor cognitive impairment fatigue pain last two decades noninvasive brain stimulation nibs especially transcranial direct current stimulation tdcs increasingly used modulate brain function various physiological pathological conditions however experimental applications people ms pwms noted early 2010 growing since efficacy use pwms remains questionable results existing studies largely conflicting hence aim review paint picture current state tdcs ms research grounded studies applying tdcs done datemethods performed keyword search retrieve articles earliest article identified 14th february 2021 using combination groups 1 multiple sclerosis ms encephalomyelitis 2 tdcs transcranial direct current stimulationresults analysis 30 articles included review underlined inconsistent effects tdcs motor symptoms ms based small sample sizes however tdcs showed promising benefits ameliorating fatigue pain cognitive symptomsconclusion tdcs attractive nondrug approach ameliorating ms symptoms treatment options remain limited development protocols tailored individuals neuroanatomy using high definition tdcs introduction network mapping experimental designs might help overcome variability studiespmid34725881 doi101111 ene15163,0.0
overlap autoimmune syndrome primary progressive multiple sclerosis primary biliary cirrhosis raynaud phenomena digital necrosis acta neurol belg 2021 nov 1 doi 101007 s13760021018339 online ahead printno abstractpmid34724168 doi101007 s13760021018339,0.0
emerging role noncoding rnas neuroinflammation implications pathogenesis therapeutic approaches j cell physiol 2021 nov 1 doi 101002 jcp30624 online ahead printabstractnoncoding rnas ncrnas important regulators gene expression different cell processes due ability monitoring neural development genes transcripts confer neurons potential exert broad control expression genes performing neurobiological functions although change ncrna expression different neurodegenerative diseases reviewed elsewhere recent evidence drove attention unravel involvement molecules neuroinflammation within devastating disorders remarkably interactions ncrnas inflammatory pathways fully recognized therefore review focused interplay diverse inflammatory pathways related ncrnas including micrornas long noncoding rnas competing endogenous rnas alzheimers disease parkinsons diseases amyotrophic lateral sclerosis epilepsy multiple sclerosis huntingtons disease prion diseases providing novel insights field combining biomarkers critical step using diagnostic tools therapeutic targets clinical settingspmid34724212 doi101002 jcp30624,0.0
alemtuzumabinduced autoimmune thyroid events patients relapsingremitting multiple sclerosis reallife monocentric experience tertiarylevel centre clin endocrinol oxf 2021 nov 1 doi 101111 cen14616 online ahead printabstractobjective alemtuzumabinduced autoimmune thyroid events aiates common adverse effects observed relapsingremitting multiple sclerosis rrms patients study aims explore clinical biochemical characteristics aiates examine risk factors occurrence particularly worst clinical phenotype fluctuating graves disease gd design patients measurements retrospectively analysed reallife singlecentre consecutive series 57 rrms patients treated alemtuzumab whose clinical biochemical parameters collected starting treatment monthly followupresults aiates developed 39 patients mean 17 months 11 first cycle alemtuzumab common aiates gd 64 followed hashimotos thyroiditis hypothyroidism 23 tshreceptorantibody trab positive hypothyroidism 9 silent thyroiditis 4 gd showed fluctuating course 57 cases baseline positivity antithyroperoxidase antibodies higher absolute titers antithyroglobulin antithyroperoxidase antibodies correlated significantly risk developing aiates trab positivity higher trab titers time gd diagnosed correlated strongly greater risk fluctuating gd phenotype roc curve analysis found cutoff 73 iu l used predict risk developing fluctuating gd positive predictive value 100conclusions trab levels measured commercial automatic methods time patient diagnosed alemtuzumabinduced gd emerged novel biomarker predicting fluctuating disease phenotype influence subsequent therapeutic decisions patients followuppmid34724236 doi101111 cen14616,0.0
quot walking tightropequot grounded theory approach informal caregiving amyotrophic lateral sclerosis health soc care community 2021 oct 31 doi 101111 hsc13625 online ahead printabstractinformal caregivers mainly family members friends provide supportive palliative care people amyotrophic lateral sclerosis als terminal disease course informal caregiving people als continues towards palliative care endoflife care progression disease study provide theoretical understanding informal caregiving als utilising 23 semistructured interviews conducted informal caregivers people als pwals switzerland due expected death care recipient grounded theory approach outlines informal caregivers caregiving work effort secure balance amongst different caregiving activities feed final stage providing palliative care overall theoretical understanding als informal caregiving work encompasses core category holding balance four secondary categories organising support present managing everyday life keeping als core category holding balance underlines significance ensuring care normalcy even disease progresses end life informal caregivers balancing act key element care provision pwals therefore guides decisions surrounding caregiving understanding caregivers succeed holding balance can provide care home death balance heavily influenced contextual factors caregiving example relating personal characteristics caregiver activities caregiving goal ensure quality life pwals heterogeneity speed subtype progression als work accounts multiple caregiving trajectoriespmid34719073 doi101111 hsc13625,0.0
socioeconomic disparity associated faster retinal neurodegeneration multiple sclerosis brain 2021 oct 29awab342 doi 101093 brain awab342 online ahead printabstractdisease course multiple sclerosis notably heterogenous prognostic indicators consistently associated multiple sclerosis severity general population socioeconomic disparity associated multimorbidity may contribute worse disease outcomes multiple sclerosis herein assessed whether indicators socioeconomic status ses associated disease progression people multiple sclerosis using highly sensitive imaging tools like optical coherence tomography oct determined differential multiple sclerosis management comorbidity mediate observed sesassociated effects included 789 participants longitudinal oct low contrast letter acuity lcla 125 25 neighborhood derived via 9digit postal codes participantlevel ses indicators available 10 years ms symptom onset sensitivity analyses included participants ses indicators available 3years symptom onset n 552 neighborhoodlevel indicators included state national area deprivation indices adi median household income agency healthcare research quality ahrq ses index participantlevel indicators included education level biannual oct scans segmented quantify thickness composite macular ganglion cell+inner plexiform layer gcipl assessed association ses indicators gcipl atrophy lcla loss using mixed models adjusting demographic including race ethnicity diseaserelated characteristics also assessed ses indicators relation multiple sclerosis therapy changes comorbidity risk using survival analysis disadvantaged neighborhoodlevel patientlevel ses indicators associated faster retinal atrophy differences rate gcipl atrophy individuals top quartile disadvantaged relative bottom quartile least state adi 012 m year faster 95ci 019 004 p 0003 national adi 008 m year faster 95ci 015 0005 p 002 household income 011 m year faster 95ci 019 003 p 0008 ahrq ses index 012 m year faster 95 ci 019 004 education level 017 m year faster 95ci 026 008 p 00002 similar associations observed ses indicators lcla loss lower ses associated higher risk incident comorbidity followup low ses individuals faster rates therapy escalation suggesting association ses gcipl atrophy may explained differential contemporaneous multiple sclerosis therapy management conclusion socioeconomic disparity associated faster retinal neurodegeneration multiple sclerosis low ses associated higher risk incident comorbidities may adversely affect multiple sclerosis outcomes comorbidity prevention may mitigate unfavorable sesassociated consequencespmid34718423 doi101093 brain awab342,0.0
smartphonederived keystroke dynamics sensitive relevant changes multiple sclerosis eur j neurol 2021 oct 31 doi 101111 ene15162 online ahead printabstractbackground investigate smartphone keystroke dynamics kd derived regular typing sensitivity relevant change disease activity fatigue clinical disability multiple sclerosis ms methods preplanned interim analysis cohort study 102 ms patients assessed baseline 3month followup gadoliniumenhancing lesions mri relapses fatigue clinical disability outcomes keyboard interactions unobtrusively collected typing using neurokeys app interactions 15 keystroke features derived aggregated using 16 summary time series statistics responsiveness kd clinical anchorbased change assessed calculating area receiver operating characteristic curve auc optimal cutpoint used determine minimal clinically important difference mcid compared smallest real change src commonly used clinical measures analyzed comparisonresults 94 patients completed followup five best performing keystroke features aucvalues ranging 072 078 change gadoliniumenhancing lesions 067070 checklist individual strength fatigue subscale 066079 expanded disability status scale 069073 ambulation functional system 072075 arm function ms questionnaire mcid features exceeded src group level kd higher aucvalues comparative clinical measures study outcomes aside ambulatory functionconclusions kd demonstrated good responsiveness changes disease activity fatigue clinical disability ms detected important change beyond measurement error group level responsiveness kd better commonly used clinical measurespmid34719076 doi101111 ene15162,0.0
pivotal trials multiple sclerosis similarities prove useful neurol ther 2021 oct 30 doi 101007 s4012002100291y online ahead printabstractwe present commentary inclusion criteria outcome measures major randomized trials multiple sclerosis qualitative comparison characteristics enrolled patients done objective stimulate discussion need improve research strategies discovery new drugs studied without personalized criteria allow useful advances knowledgepmid34718965 doi101007 s4012002100291y,0.0
population pharmacokinetic modeling inebilizumab subjects neuromyelitis optica spectrum disorders systemic sclerosis relapsing multiple sclerosis clin pharmacokinet 2021 oct 31 doi 101007 s40262021010715 online ahead printabstractbackground objective inebilizumab humanized affinityoptimized afucosylated immunoglobulin ig g1 monoclonal antibody binds cd19 resulting effective depletion peripheral b cells developed treat various autoimmune diseases including neuromyelitis optica spectrum disorders nmosd systemic sclerosis ssc relapsing multiple sclerosis ms methods pharmacokinetic data pivotal study adult subjects nmosd two earlystage studies subjects ssc relapsing ms pooled simultaneously analyzed using population approachresults upon intravenous administration pharmacokinetics inebilizumab adequately described twocompartment model parallel firstorder timedependent nonlinear elimination pathways asymptotic nonlinear elimination suggests inebilizumab undergoes receptor cd19 mediated clearance estimated systemic clearance cl firstorder elimination pathway 0188 l day volume distribution vd 552 l typical therapeutic immunoglobulins elimination halflife approximately 18 days maximum velocity vmax nonlinear elimination pathway decreased time presumably due depletion b cells upon inebilizumab administration therapeutic monoclonal antibodies cl vd inebilizumab increased body weightconclusions presence antidrug antibodies status hepatic renal function use smallmolecule drugs commonly used subjects nmosd clinically relevant impact pharmacokinetics inebilizumab nonlinear elimination pathway 300 mg therapeutic dose level considered clinically relevantpmid34718986 doi101007 s40262021010715,0.0
spectrum sublytic astrocytopathy neuromyelitis optica brain 2021 oct 30awab394 doi 101093 brain awab394 online ahead printabstractneuromyelitis optica autoimmune inflammatory disorder targeting aquaporin4 water channels cns astrocytes histopathologic descriptions astrocytic lesions reported neuromyelitis optica date emphasized characteristic loss aquaporin4 deposition igg complement lysis astrocytes sublytic reactions underappreciated performed multimodality study 23 neuromyelitis optica autopsy cases clinically pathologicallyconfirmed 337 tissue blocks evaluating astrocytic morphology immunohistochemistry aqp4 rna transcripts associations demyelinating activity documented spectrum astrocytopathy addition complement deposition microglial reaction granulocyte infiltration regenerating activity within advanced demyelinating lesions periplaque areas remarkable hypertrophic astrogliosis subtle astrocytic lysis degenerative component suggested dystrophic morphology cytoplasmic vacuolation rosenthal fibres associated stress protein markers abundance aqp4 mrna transcripts sublytic reactive astrocytes devoid aquaporin4 protein supported vivo restoration following igginduced aquaporin4 endocytosis degradation astrocytic alterations extending beyond demyelinating lesions speak astrocytopathy early primary event evolving neuromyelitis optica lesion focal astrocytopathy observed without aquaporin4 loss lytic complement component deposition verifies astrocytic reactions nmo solely dependent iggmediated aquaporin4 loss lysis complement iggdependent leukocyte mediators conclude neuromyelitis optica reflects global astrocytopathy initiated binding igg aquaporin4 simply definable demyelination astrocytic lysis spectrum astrocytic morphological changes neuromyelitis optica attests complexity factors influencing range astrocytic physiological responses targeted attack aquaporin4specific igg sublytic astrocytic reactions doubt important determinant lesions evolution potential repair pharmacological manipulation astrocytic stress response may offer new avenues therapeutic interventionpmid34718426 doi101093 brain awab394,1.0
autonomic nervous system function newly diagnosed multiple sclerosis association lipid levels insulin resistance physiol res 2021 oct 30 70 6 online ahead printabstractautonomic nervous system ans disorders common multiple sclerosis ms previous studies showed differences insulin resistance ir lipoprotein levels ms subjects compared controls lipolysis caused increased sympathetic activity one possible linking mechanisms leading dyslipidemia ms study aimed evaluate ans activity context glucose lipid metabolism people ms prospectively measured shortterm heart rate variability hrv fasting lipoprotein concentrations calculated ir indices based plasma glucose insulin levels oral glucose tolerance test ogtt 32 patients ms 29 healthy controls matched age sex body mass index study significant difference hrv parameters lipoprotein levels ms controls significant positive correlation found low highfrequency power ratio lf hf triglycerides r0413 p0021 ms subjects controls significantly lower wholebody insulin sensitivity index isimat found patients ms compared control group 7337 vs 9856 p0041 significant correlations found lf hf ir parameters ms subjects positive correlation lf hf triglycerides reflect effects sympathetic activity lipolysis positive correlations sympathetic activity increased lipoprotein levels rather reflect processes associated immune system activation inflammation processes involved glucose homeostasis maintenancepmid34717060,0.0
performance 2017 2010 revised mcdonald criteria predicting ms diagnosis clinically isolated syndrome magnims study neurology 2021 oct 29101212 wnl0000000000013016 doi 101212 wnl0000000000013016 online ahead printabstractbackground objectives compare performance 2017 revisions mcdonald criteria 2010 mcdonald criteria establishing ms diagnosis predicting prognosis patients clinically isolated syndrome cis suggestive multiple sclerosis ms methods csf examination brain spinal cord mri obtained 5 months cis onset followup brain mri acquired within 15 months cis onset evaluated 785 cis patients 9 european centers date second clinical attack reaching expanded disability status score edss 30 occurred also collected performance 2017 2010 mcdonald criteria dissemination space dis time dit including oligoclonal bands assessment dis + dit predicting second clinical attack clinically definite cd ms edss 30 followup evaluated time ms diagnosis different criteria also estimatedresults followup median 691 months 406 785 cis patients developed cdms 36 months 2017 dis + dit criteria higher sensitivity 083 vs 066 lower specificity 039 vs 060 similar area curve values 061 vs 063 median time ms diagnosis shorter 2017 vs 2010 cdms criteria 2017 revision 32 2010 revision 130 cdms 585 months 2 sets criteria similarly predicted edss 30 milestone three periventricular lesions improved specificity patients 45 yearsdiscussion 2017 mcdonald criteria showed higher sensitivity lower specificity similar accuracy predicting cdms compared 2010 mcdonald criteria shortening time diagnosis msclassification evidence study provides class ii evidence 2017 mcdonald criteria accurately distinguish cdms patients early cis compared 2010 mcdonald criteriapmid34716250 doi101212 wnl0000000000013016,0.0
insights extracellular vesicles mesenchymal stem cells prospective cellfree regenerative medicine neurodegenerative disorders mol neurobiol 2021 oct 29 doi 101007 s12035021026037 online ahead printabstractmesenchymal stem cells mscs multipotent adult stem cells found numerous tissues like umbilical cord whartons jelly bone marrow adipose tissue possess capacity selfrenewal dividing differentiating various cellular lineages characteristic therapeutic potential exploited far made desirable candidate regenerative medicine neurodegenerative diseases nds like alzheimers disease ad parkinsons disease pd huntingtons disease hd amyotrophic lateral sclerosis als ischemic stroke treated mscs mscderived products past decades witnessed significant contributions discovering etiology various nds possible therapeutic solutions one mscbased therapeutics extracellular vesicles evs contain multiple biologically active molecules like nucleic acids proteins contents evs ferried cells intercellular communication leads regulation homeostasis recipient cells evs serve considerable means cellfree therapies like tissue repair regeneration evs can maintain therapeutically effective cargo parent cells free various ethical issues cellbased therapies due paucity standard protocols extraction procedures evs pharmacological properties mechanisms development new ev dependent therapies challenging review attempt made annotate mechanisms can help advance novel therapeutic approaches towards treat define narrowed approach nd devise effective mscbased therapies cure avert diseasespmid34714469 doi101007 s12035021026037,1.0
effects pregnancy breastfeeding clinical outcomes mri measurements women multiple sclerosis exploratory realworld cohort study neurol ther 2021 oct 29 doi 101007 s40120021002976 online ahead printabstractintroduction pregnancy represents important event women multiple sclerosis ms often accompanied postpartum disease reactivation date influence reproductive phase longterm ms outcomes still largely unexplored objective study characterise large realworld cohort women ms evaluate effects pregnancy breastfeeding short longterm clinical magnetic resonance imaging mri outcomes exploring relationships mri measurements brain atrophymethods ms patients without pregnancy recruited clinical relapses mri activity year conception versus year delivery evaluated regression models performed investigate relationships longterm ms outcomes edss score mri brain measurements obtained sienax software pregnancy breastfeeding durationresults two hundred ten women ms enrolled 129 614 least one pregnancy pregnancies n 212 occurred ms onset 90 424 examined evaluate shortterm outcomes higher annualised relapse rate postpartum year versus preconception year 054 084 vs 045 071 p 004 observed regression analysis showed clinical activity delivery associated clinical activity year conception p 0001 well duration breastfeeding p 0022 similarly postpartum mri activity associated preconception mri activity p 0026 shorter breastfeeding duration p 0013 regarding longterm outcomes least one pregnancy ms associated lower edss score p 0021 relationships reported mri measurements conversely breastfeeding duration 6 months associated lower white matter volume p 0008 conclusions study underlines importance considering effects pregnancy breastfeeding short longterm ms outcomes current therapeutic landscape pregnancy planning treatment optimisation postpartum period particular women choose breastfeed fundamental management biological phases central womans lifepmid34714518 doi101007 s40120021002976,0.0
new pharmaceuticals approved fda 2020 smallmolecule drugs derived amino acids related compounds chirality 2021 oct 29 doi 101002 chir23376 online ahead printabstractamino acids aas play important role modern health industry key synthetic precursors pharmaceuticals biomaterials biosensors drug delivery systems currently 30 smallmolecule drugs contain residues tailormade aas derived aminoalcohols diamines review article profile 12 aaderived new pharmaceuticals approved fda 2020 newly introduced drugs include tazverik epithelioid sarcoma gemtesa overactive bladder zeposia multiple sclerosis byfavo induction maintenance procedural sedation cu 64 dotatate gallium 68 psma11 pet imaging rimegepant acute migraine zepzelca lung cancer remdesivir covid19 amisulpride nausea vomiting setmelanotide obesity lonafarnib progeria syndrome compound describe spectrum biological activity medicinal chemistry discovery synthetic preparationpmid34713503 doi101002 chir23376,0.0
functional network dynamics decreased conscientiousness multiple sclerosis j neurol 2021 oct 29 doi 101007 s00415021108608 online ahead printabstractbackground conscientiousness personality trait declines people multiple sclerosis pwms decline predicts worse clinical outcomes study aims investigate neural underpinnings lower conscientiousness pwms examining mri anomalies functional network dynamicsmethods 70 pwms 50 healthy controls underwent personality assessment restingstate mri associations dynamic functional network properties ie eigenvector centrality evaluated using dynamic slidingwindow approachresults pwms lower conscientiousness associated increased variability centrality left insula tmax 421 right inferior parietal lobule tmax 379 relationship also observed regressions accounting handedness disease duration disability tract disruption relevant structural networks r2 0071 p 0003 r2 0094 p 0004 centrality dynamics observed regions associated neuroticism r2 0001 p 0956 r2 0001 p 0945 well higher conscientiousness associated greater variability connectivity left insula defaultmode network f 392 p 0023 limbic network f 566 p 0005 conclusion lower conscientiousness pwms associated increased variability network centrality prominently left insula right inferior parietal cortex effect specific conscientiousness significant accounting disability structural network damage indicate overall stable network centrality lost patients low conscientiousness especially insula right parietal cortex positive relationship conscientiousness variability connectivity left insula defaultmode network potentially affirms dynamics salience defaultmode networks related regulation behaviorpmid34713325 doi101007 s00415021108608,0.0
three strategies physicians provide complex information interactions patients recognize measure patient educ couns 2021 oct 13s07383991 21 00673x doi 101016 jpec202110013 online ahead printabstractobjective define operationalize three taught strategies providing information interactions patients using videos collected randomized controlled trial rct methods qualitative exploratory study embedded randomized controlled design using microanalysis facetoface dialogue inductive video analysis method operationalize physicians use three informationprovision strategies data 34 videorecorded simulated unscripted interactions 17 physicians 34 multiple sclerosis patients collected brief course information provision operationalized 1 mapping patients preferences 2 checking patients understanding pauses indicative 3 portioning informationresults results detailed analytical definitions criteria assessable quantifiable outcomes three strategies patients responded portioning pauses expected whereas 91 pauses elicited immediate patient response 23 nonportioning pauses soconclusion methods revealed define evaluate information sharing strategies physicians used within contingencies clinical interactionpractice implications findings provide applicable methods teach analyze evaluate information sharing strategies indications trainingpmid34711445 doi101016 jpec202110013,0.0
hepatocytic p62 suppresses ductular reaction tumorigenesis mouse livers mtorc1 activation defective autophagy j hepatol 2021 oct 25s01688278 21 021516 doi 101016 jjhep202110014 online ahead printabstractbackground aims either activation mtorc1 due loss tsc1 tuberous sclerosis complex 1 defective hepatic autophagy due loss atg5 leads spontaneous liver tumorigenesis mice purpose study investigate mechanisms autophagy impacts mtorc1 activationmediated liver metabolic changes tumorigenesismethods atg5 flox flox atg5f f tsc1f f mice crossed albumin cre mice generate liverspecific atg5 knockout latg5 ko ltsc1 ko latg5 tsc1 double ko dko mice mice crossed p62 sqstm1f f p62 whole body nrf2 ko mice generate latg5 tsc1 p62 latg5 tsc1 nrf2 triple ko tko mice mice housed various time points 12 months blood liver tissues harvested biochemical histological analysis results deletion atg5 ltsc1 ko mice inhibited liver tumorigenesis increased mortality ltsc1 ko mice accompanied drastically enhanced hepatic ductular reaction dr hepatocyte degeneration metabolic reprogramming deletion p62 reversed dr hepatocyte degeneration metabolic reprogramming well mortality latg5 tsc1 dko mice unexpectedly promoted liver tumorigenesis via activation group oncogenic signaling pathways nrf2 ablation markedly improved dr increased hepatocyte population improved metabolic reprogramming survival l atg5 tsc1 dko mice without tumor formation decreased p62 increased mtor activity also found subset human hepatocellular carcinomaconclusions results reveal previously undescribed functions hepatic p62 suppressing tumorigenesis regulating liver cell repopulation metabolic reprogramming resulting persistent mtorc1 activation defective autophagylay summary metabolic liver disease viral hepatitis common chronic liver diseases risk factors hepatocellular carcinoma often associated impaired hepatic autophagy increased mtor activation using multiple genetic engineered mice defective hepatic autophagy persistent mtor activation dissected complex interplay among mtor autophagy p62 nrf2 liver cell repopulation metabolic reprogramming redox homeostasis liver tumorigenesis results uncovered unexpected novel tumor suppressor function p62 sqstm1 regulating liver cell repopulation ductular reaction metabolic reprogramming liver tumorigenesispmid34710483 doi101016 jjhep202110014,0.0
astrocytic outer retinal layer thinning feature aqp4igg seropositive neuromyelitis optica spectrum disorders j neurol neurosurg psychiatry 2021 oct 28jnnp2021327412 doi 101136 jnnp2021327412 online ahead printabstractbackground patients antiaquaporin4 antibody seropositive aqp4igg+ neuromyelitis optica spectrum disorders nmosds frequently suffer optic neuritis leading severe retinal neuroaxonal damage relationship retinal damage primary astrocytopathy nmosd uncertain primary astrocytopathy suggested cause onindependent retinal damage contribute changes particularly outer plexiform layer opl outer nuclear layer onl reported earlier studies however limited sample size contradictory localisation study assesses outer retinal layer changes using optical coherence tomography oct multicentre crosssectional cohortmethod 197 patients aqp4igg+ 32 myelinoligodendrocyteglycoprotein antibody seropositive mogigg+ patients enrolled study along 75 healthy controls participants underwent neurological examination oct central postprocessing conducted single siteresults significant thinning opl 2502203 m onl 6163704 m observed patients aqp4igg+ compared patients mogigg+ comparable neuroaxonal damage opl 2510200 m onl 6471787 m healthy controls opl 2458164 m onl 6359578 m eyes patients aqp4igg+ 1984509 m p0027 mogigg+ 1982478 m p0004 history showed parafoveal opl thinning compared healthy controls 2099514 m observed elsewhereconclusion results suggest outer retinal layer loss consistent component retinal astrocytic damage aqp4igg+ nmosd longitudinal studies necessary determine opl onl damaged late disease due retrograde transsynaptic axonal degeneration whether outer retinal dysfunction occurs despite measurable structural correlatespmid34711650 doi101136 jnnp2021327412,1.0
trpa1 mediates headacherelated cephalic allodynia mouse model relapsingremitting multiple sclerosis pain 2021 oct 26 doi 101097 jpain0000000000002520 online ahead printabstractprimary headache conditions frequently associated multiple sclerosis ms mechanism triggers worsens headaches ms patients poorly understood previously showed proalgesic transient receptor potential ankyrin 1 trpa1 mediates hind paw mechanical cold allodynia relapsingremitting experimental autoimmune encephalomyelitis rreae model mice investigated development periorbital mechanical allodynia pma rreae hallmark headache trpa1 contributed response rreae induction injection myelin oligodendrocyte peptide fragment 3555 mog3555 quillaja adjuvant quil c57bl 6j female mice elicited delayed sustained pma pma day 35 induction reduced calcitonin generelated peptide cgrp receptor antagonist olcegepant serotonin 5ht1b d receptor agonist sumatriptan two known antimigraine agents genetic deletion pharmacological blockade trpa1 attenuated pma associated rreae levels oxidative stress biomarkers 4hydroxynonenal hydrogen peroxide known trpa1 endogenous agonists superoxide dismutase nadph oxidase activities increased trigeminal ganglion rreae mice besides treatment antioxidants apocynin lipoic acid attenuated pma thus results study indicate trpa1 presumably activated endogenous agonists evokes pma mouse model relapsingremitting mspmid34711761 doi101097 jpain0000000000002520,1.0
long noncoding rna gas5 agerelated diseases curr med chem 2021 oct 27 doi 102174 0929867328666211027123932 online ahead printabstractaging refers natural process universal phenomenon cells tissues organs whole organism long noncoding rnas lncrnas noncoding rnas length 200 nucleotides lncrna growth arrestspecific 5 lncrna gas5 often downregulated cancer accumulation lncrna gas5 found able inhibit cancer growth invasion metastasis enhancing sensitivity cells chemotherapy drugs lncrna gas5 can signaling protein specifically transcribed different triggering conditions subsequently involved signal transmission numerous pathways signal node lncrna gas5 close relationship multiple mirnas suggested involved signaling pathway three action modes ie signal bait guidance lncrna gas5 found involved different agerelated diseases eg rheumatoid arthritis type 2 diabetes atherosclerosis osteoarthritis osteoporosis multiple sclerosis cancer etc study mainly summarized regulatory effect exerted lncrna gas5 agerelated diseasespmid34711157 doi102174 0929867328666211027123932,0.0
monocytes central nervous system remyelination glia 2021 oct 28 doi 101002 glia24111 online ahead printabstractremyelination failure aging progression neurodegenerative disorders contributes axonal dysfunction highlighting importance understanding mechanisms underpinning process develop regenerative therapies central nervous system cns macrophages encompassing resident microglia blood monocytederived cells play crucial role driving successful remyelination although focus critical roles microglia remyelination specific contribution monocytederived macrophages still fully understood recently lack tools enabling distinction cns macrophage populations hindered understanding monocyte influence remyelination recent advances allowed identification characterization monocyte populations health aging neurodegenerative conditions like multiple sclerosis indicating heterogeneity monocyte subsets impacted intrinsic extrinsic factors discuss new tools enabling distinction macrophage populations advancements understanding importance monocytes remyelination reflect potential therapeutic targeting monocytes promote remyelinationpmid34708884 doi101002 glia24111,1.0
effect exercise balance patients stroke parkinson multiple sclerosis systematic review metaanalysis clinical trials neurol sci 2021 oct 28 doi 101007 s1007202105689y online ahead printabstractbackground stroke parkinson multiple sclerosis range diseases affecting nervous system show balance impairments due damage balance control system many early articles published effect exercise balance patients suffering neuromuscular diseases however comprehensive study showing clear result three diseases found hence purpose present metaanalysis systematic review determine effect exercise balance people stroke parkinson multiple sclerosismethods according prisma 2009 multistep instructions keywords related purpose research browsed mesh browser databases irandoc magiran iranmedex sid sciencedirect web science wos proquest medline pubmed scopus google scholar searched extract articles published persian english language search process retrieving articles sources mentioned january 01 2000 december 30 2020 done heterogeneity index studies determined using i2 test given heterogeneity randomeffects model used combine articles resultsresults initially 7067 articles found removing duplicate irrelevant articles 96 clinical trials sample size intervention group 1760 people included study result articles composition mean balance score index exercise intervention group showed significant increase 067 012 unit p001 highest rate increase balance score intervention reported patients myelomeningocele 166 03 unit p001 conclusion considering positive effect using exercise increasing balance patients stroke parkinson multiple sclerosis recommended health care providers implement regular exercise program improve condition patientspmid34709478 doi101007 s1007202105689y,0.0
serum levels genetic variation il35 associated multiple sclerosis populationbased casecontrol study immunol res 2021 oct 27 doi 101007 s12026021092469 online ahead printabstractthis study aimed investigate association serum levels polymorphic variants il35 susceptibility clinical features disease severity multiple sclerosis ms patientsthis casecontrol study recruited 186 ms patients 195 sex agematched healthy controls serum levels polymorphic variants il35 determined elisa restriction fragment length polymorphism rflp pcr high resolution melting hrm analysis methods respectively addition silico analysis evaluated location function polymorphismserum levels il35 significantly lower patients healthy controls 493 37 vs 695 78 p 0009 ebi3 rs4740 polymorphism il35 associated 22fold increased risk ms susceptibility 95 ci 1339 p 0005 however differences genotype distribution allele frequencies il35 rs568408 patients controls p 005 silico results showed variation il12a ebi3 may affect protein pathways cells different components immune system nfb infthe results show il35 polymorphisms might genetic risk factor development mspmid34708312 doi101007 s12026021092469,0.0
threeyear longitudinal study retinal function structure patients multiple sclerosis doc ophthalmol 2021 oct 27 doi 101007 s10633021098557 online ahead printabstractbackground researchers recent years begun investigate ophthalmological manifestations multiple sclerosis ms optic neuritis now clear changes retinal function measured using electroretinogram erg structure measured using optical coherence tomography oct found ms patients irrespective prior episodes erg results consistent dysfunctional bipolar cells autoimmune diseases date studies presented crosssectional data regarding erg oct therefore studied longitudinal course erg oct patients ms well effect disability changes nonon clinical relapses functional structural measuresmethods ms patients n 23 participating ongoing longitudinal observational study invited take part 3year ophthalmological substudy erg oct performed measures msrelated disability relapse history obtained study visits repeated annually erg peak times rod bwave amplitude mixed rod cone cone b awave amplitude ratios thickness peripapillary retinal nerve fibre layer volumes segmented retinal layers complexes analysed using generalised estimating equation models adjusted age ms treatment status assessed changes erg oct study duration effect changes disability recent nonon ms relapses erg oct effect selected oct parameters corresponding erg parametersresults group level small fluctuations several erg peak times recorded oct values remaining stable increased disability visits associated significant prolongation mixed rodcone erg bwave peak times evidence associations oct erg parameters observedconclusions retinal bipolar cell function may affected changes disability patients ms however recent nonon ms clinical relapses appear affect erg oct results erg changes ms patients 3 years likely small uncertain clinical relevance longitudinal studies retinal function ms planned extended periodpmid34705132 doi101007 s10633021098557,0.0
k2p181 translates t cell receptor signals thymic regulatory t cell development cell res 2021 oct 26 doi 101038 s4142202100580z online ahead printabstractit remains largely unclear thymocytes translate relative differences t cell receptor tcr signal strength distinct developmental programs drive cell fate decisions towards conventional tconv regulatory t cells treg following tcr activation intracellular calcium ca2+ important second messenger potassium channel k2p181 relevant regulator identify k2p181 central translator tcr signal thymusderived treg ttreg selection process tcr signal coupled nfbmediated k2p181 upregulation ttreg progenitors k2p181 provided driving force sustained ca2+ influx facilitated nfb nfatdependent expression foxp3 master transcription factor treg development function loss k2p181 ioncurrent function induced mild lymphoproliferative phenotype mice reduced treg numbers led aggravated experimental autoimmune encephalomyelitis gainoffunction mutation k2p181 resulted increased treg numbers mice findings human thymus recent thymic emigrants multiple sclerosis patients dominantnegative missense k2p181 variant associated poor clinical outcomes indicate k2p181 also plays role human treg development pharmacological modulation k2p181 specifically modulated treg numbers vitro vivo finally identified nitroxoline k2p181 activator led rapid reversible treg increase patients urinary tract infections conclusively findings reveal k2p181 translates tcr signals thymic t cell fate decisions treg development provide basis therapeutic utilization treg several human disorderspmid34702947 doi101038 s4142202100580z,0.0
modelinformed assessment ethnic sensitivity dosage justification asian populations global clinical development use cladribine tablets clin transl sci 2021 oct 26 doi 101111 cts13166 online ahead printabstractcladribine tablets approved many countries treatment patients various forms relapsing multiple sclerosis ms cladribine unique pharmacokinetic pharmacodynamic pk pd profile short elimination halflife 1 day relative prolonged pd effect specific immune cells notably reversible reduction b t lymphocyte counts results short dosing schedule 20 days 2 years treatment sustain efficacy least another 2 years global clinical studies conducted primarily white patients part due distinctly higher prevalence ms white patients given low prevalence asian countries ms considered rare disease spite limited participation asian patients demonstrate favorable benefit risk profile treatment ms demanded application totality evidence approach assess ethnic sensitivity informing regulatory filings asian countries supporting clinical use cladribine asian patients population pd modeling simulation treatmentrelated reduction absolute lymphocyte count mechanismrelated biomarker drug effect confirmed consistent pds asian nonasian patients ms supporting absence ethnic sensitivity common dosage across populations example demonstrate value holistic integration available data using modelinformed drug development midd framework totality evidence mindset evaluate ethnic sensitivity support asiainclusive development use drug across populationspmid34704362 doi101111 cts13166,0.0
primary progressive multiple sclerosis overlapping antigad antihu antibodies positive neurological syndromes neurol neurochir pol 2021 oct 27 doi 105603 pjnnsa20210078 online ahead printno abstractpmid34704603 doi105603 pjnnsa20210078,0.0
comparison radiation toxicity outcomes patients without autoimmune diagnoses requite study int j radiat oncol biol phys 2021 nov 1 111 3s e238 doi 101016 jijrobp202107808abstractpurpose objective s requite study multicenter prospective observational study includes standardized radiotherapy data nongenetic risk factor data biobank data including common genetic variants may provide important information differences radiation toxicity predictive biomarkers amongst patients autoimmune disease goal analysis determine association late toxicity outcomes autoimmune disease phenotypes requite study cohort use determining autoimmunerelated genomic predictors toxicitiesmaterials methods compared late radiation toxicity prostate cancer patients without autoimmune phenotype autoimmune diagnoses included systemic lupus erythematosus collagen vascular disease rheumatoid arthritis inflammatory bowel disease autoimmune disorders eg multiple sclerosis probability symptom worsening baseline 1224 months determined proctitis rectal bleeding hematuria urinary obstruction incontinence frequency retention erectile dysfunction ejaculation disorder orgasmic dysfunction adjusted estimates association autoimmune phenotype late toxicity modeled multivariable logistic regression adjusting multiple comparisons false discovery rate t 010 models adjusted toxicity progressive disease risk factors including comorbidities heart disease hypertension diabetes hemorrhoids smoking treatment modality prior turp radical prostatectomy hormone therapy age patients maximal scores 3 4 3 3 2 2 baseline excludedresults 1441 prostate cancer patients treated radiotherapy 76 53 autoimmune phenotype reported likely also hypertension among patients baseline longitudinal scores common toxicities included sexual toxicity erectile dysfunction n 475 945 50 ejaculation disorder n 373 787 47 orgasmic dysfunction n 324 760 43 urinary frequency n 396 1311 30 incontinence n 282 1313 21 proctitis n 224 1331 17 rectal bleeding n 218 1329 16 adjusted estimates demonstrate independent association autoimmune disease proctitis 23 95 ci 130388 p 0003 q 002 rectal bleeding 20 ci 111348 p 002 q 007 rectal bleeding current smoking 45 ci 2579 p 001 q 005 hypertension 066 ci 4889 p 001 q 005 protectiveconclusion certain gastrointestinal radiation treatmentrelated toxicities associated autoimmune phenotype patients treated prostate cancer large prospective cohort next step includes performing analysis candidate genes addition polygenic risk score predicting toxicitypmid34700988 doi101016 jijrobp202107808,0.0
post srs target diffusion metrics response prognostication idiopathic trigeminal neuralgia int j radiat oncol biol phys 2021 nov 1 111 3s e76e77 doi 101016 jijrobp202107440abstractpurpose objective s diffusion tensor imaging dti used measure movement water molecules biological tissue permits thorough characterization white matter microstructure quantitative diffusivity metrics commonly used diffusivity metric fractional anisotropy fa provides insight overall white matter microstructural properties whereas radial diffusivity rd axial diffusivity ad mean diffusivity md suggest changes myelination axonal integrity underlying neuroinflammation edema respectively study purpose find whether trigeminal nerve diffusivity metrics single early time point frameless srs predictive longterm pain relief patients tnmaterials methods study cohort comprised 44 pts inclusion criteria 1 diagnosis classic type 1 tn 2 srs treatment prior surgical procedures tn 3 3 tesla mri scans 6 months posttreatment range 57 months 4 least 12 months clinical followup patients tn secondary multiple sclerosis cranial tumors vertebrobasilar dolichoectasia compressing brainstem excluded study patient diffusivity metrics fa md rd ad extracted affected unaffected trigeminal nerves 6 months posttreatment 6 months diffusivity metrics compared longterm clinical outcome patients identified longterm responders achieved least 75 reduction preoperative pain 12 months longer following srs average microstructural diffusivity differences within group pre post treatment across group responder nonresponders analyzed using paired independent t testresults trigeminal nerve diffusivity 6 months postsrs predictive longterm clinical effectiveness longterm responders n 36 showed significantly lower fractional anisotropy radiosurgical target affected nerve compared contralateral unaffected nerve nonresponders radial diffusivity mean diffusivity correlates myelin alterations inflammation also significantly higher affected nerve longterm responders compared unaffected nerve nonresponders n 8 exhibit characteristic diffusivity changes srsconclusion dti fa specifically appears strong objective measure assess effects radiation nerve incorporating early dti assessment can provide prognostic information supplements clinical measurespmid34701964 doi101016 jijrobp202107440,1.0
relevance competences healthy physically active lifestyle persons multiple sclerosis path analytical approach behav med 2021 oct 26111 doi 101080 0896428920211935437 online ahead printabstractto promote health counteract decline associated disease persons multiple sclerosis pwms advised lead healthy physically active lifestyles physical activityrelated health competence pahco model posits individuals must meet three integrated personrelated requirements adoption lifestyle movement competence control competence selfregulation competence gain insights needs challenges pwms goal present study empirically examine roles competences within target group total 475 pwms underwent multidimensional onlinebased assessment pahco participants selfreported amount physical activity pa health status diseaserelated sociodemographic information used series path analyses investigate relevance three competence areas individuals pa level subjective health stepwise multivariate analyses revealed selfregulation competence significantly associated overall pa volume contrast movement competence contribute prediction control competence also related pa level however accordance pahco model factor exerted independent qualitative effect participant health summary selfregulation competence appears play crucial role regard pa volume specifically control competence appears key qualitative aspect pa promotion characterizing individuals application appropriate stimulus achievement health integrating promotion selfregulation control competences rehabilitation practices can help foster healthy physically active lifestyles pwmssupplemental data article available online https doiorg 101080 0896428920211935437 pmid34702133 doi101080 0896428920211935437,1.0
sociodemographic predictors stage iv breast cancer presentation vulnerable patient population int j radiat oncol biol phys 2021 nov 1 111 3s e325 doi 101016 jijrobp202107999abstractpurpose objective s socially disadvantaged populations united states experience worse outcomes compared general population diagnosed breast cancer one potentially vulnerable population includes patients age 65 qualify medicare due debilitation group includes patients received social security disability insurance least 2 years diagnosed endstage renal disease amyotrophic lateral sclerosis current literature suggests population experiences worse oncologic outcomes national cancer database ncdb analyzed determine factors among patients age 65 qualify medicare predict higher likelihood presenting stage iv breast cancermaterials methods ncdb queried breast cancer patients diagnosed 20042014 age 65 qualified medicare patients excluded presented noninvasive disease ajcc stage unknown patients excluded social determinants race income quartiles charlsondeyo comorbidity score travel distance hospital factors facility type facility location unknown pearson chisquare test used identify associations categorial variables stage univariate analysis sociodemographic factors performed statistically significant factors included multinomial logistic regression model determine independent covariates associated stage iv presentationresults 56 964 patients met study criteria based p values p 005 strength odds ratios following variables included final model race income comorbidity score travel distance facility type facility location covariates except facility location distance significant predictors metastatic disease presentation race significant predictor white patients less likely stage iv presentation 073 p 0001 compared black patients individuals earning 38 000 annually significantly likely present stage iv 115 p 0001 patients traveled shorter distances treatment facility nonsignificantly higher odds presenting stage iv 137 p 0608 higher comorbidity score significant predictor stage iv disease presentationconclusion multiple sociodemographic factors powerful predictors stage iv breast cancer presentation select population patients 65 years old qualify medicare due debilitation deeper understanding factors can help identify patients high risk metastatic cancer presentation order provide screening preventative services earlier stage vulnerable populationpmid34701187 doi101016 jijrobp202107999,0.0
populationbased study association autoimmune disease lymphoma national health insurance servicenational sample cohort 20022015 korea int j radiat oncol biol phys 2021 nov 1 111 3s e300 doi 101016 jijrobp202107944abstractpurpose objective s aimed evaluate association autoimmune disease aid lymphoma incidence korean population also aimed compare overall survival os patients aidassociated lymphoma aal patients lymphoma without aidmaterials methods used national sample cohort 20022015 provided national health insurance service among 1 011 638 patients 994 496 recruited final cohort 130 987 patients 132 aid group 863 509 868 control lymphoma diagnosed 1 162 patients 322 patients accompanying aid irrespective time point diagnosis defined aal patients experienced lymphoma development least one year aid diagnosis defined postaid lymphoma n 155 results median followup duration 137 years aal accounted 003 total 277 lymphoma cases aid patients experienced epsteinbarr virus 002 vs 001 p 0027 helicobacter pylori infection 639 vs 414 p 0001 control group aid associated 145fold increased risk lymphoma median time interval aid aal 109 months risk lymphoma increased order psoriasis adjusted odds ratio aor 161 systemic lupus erythematosus aor 399 multiple sclerosis aor 452 sarcoidosis aor 2637 sjogren syndrome related lymphoma cohort 5year os aal different lymphoma patients without aid 609 vs 615 p 0970 conclusion association patterns aal korean population different western countries studies lymphomatogenesis distinct baseline characteristics eg chronic infection status elucidate difference based race ethnicitypmid34701128 doi101016 jijrobp202107944,0.0
significance serum vip pacap multiple sclerosis exploratory casecontrol study neurol sci 2021 oct 26 doi 101007 s10072021056825 online ahead printabstractbackground multiple sclerosis ms chronic inflammatory neurodegenerative disease central nervous system vasoactive intestinal peptide vip pituitary adenylate cyclaseactivating peptide pacap neuropeptides play roles antiinflammation neuroprotection ms study aimed determine serum levels vip pacap ms patients versus healthy controls correlate demographics clinical characteristicsmethods serum samples collected ms patients n 145 healthy controls n 73 measure serum levels vip pacapresults vip serum levels lower ms patients healthy controls p 0001 serum pacap levels among two groups genderbased analysis showed vip levels lower healthy females 1238840 pg ml healthy males 3300105 pg ml p 0001 pacap serum levels significantly lower male ms patients 48 516214 fg ml female ms patients 62 466400 fg ml p 0029 roc curve suggested serum vip level can discriminate patients ms healthy controls relapsingremitting ms progressivems clinically isolated syndrome groups different age ms disease duration edss score vip levels p 005 ms disease type history previous relapses preceding 24 months predicted serum vip levels gender predicted pacap levelsconclusion vip serum levels decreased ms patients can used differentiate ms patients healthy controls studies larger sample sizes required investigate vip marker reflect ms disease progressionpmid34698942 doi101007 s10072021056825,0.0
psychological wellbeing people multiple sclerosis descriptive review effects obtained mindfulness interventions neurol sci 2021 oct 25 doi 101007 s10072021056861 online ahead printabstractmultiple sclerosis neuroinflammatory neurodegenerative disease causing several psychosocial problems significantly impairs quality life common physical mental symptoms anxiety depression stress fatigue pain several studies investigated effectiveness nonpharmacological approaches improving psychological wellbeing review focused impact mindfulness interventions patients multiple sclerosis reduce psychopathological symptoms improve wellbeing searched pubmed database screening references included studies review articles additional citations initial 107 studies 8 met search criteria studies showed efficacy mindfulness treatment reduction depressive symptoms better quality life mental physical decreased level fatigue findings demonstrated mindfulness useful improvement psychological symptoms pain management improvement also shown positive impact quality life coping adaptation strategies however according poor available clinics evidence conclude mindfulness interventions superior active interventions treatment psychological symptoms smpmid34697659 doi101007 s10072021056861,0.0
iliofemoral venous stenting patients central neuromuscular disorders j vasc surg venous lymphat disord 2021 oct 22s2213333x 21 005163 doi 101016 jjvsv202110010 online ahead printabstractbackground leg swelling patients various central neuromuscular disorders common clinical scenario can lead significant morbidity aim report evaluate subset patients central neuromuscular disorders iliofemoral venous stenting performed specialty venous clinic tertiary care hospitalmethods january 2000 december 2020 records patients known central neuromuscular disorder underwent iliofemoral venous stenting chronic iliofemoral venous obstruction civo retrospectively analyzedresults 42 patients 45 limbs central neuromuscular disorders underwent iliofemoral stenting failure trial conservative therapy distribution central neuromuscular disorders parkinsons disease n20 limbs multiple sclerosis n15 limbs neuromuscular conditions n10 limbs mean age sample 59 14 years ratio postthrombotic nonthrombotic iliac vein lesions nivls 31 majority patients ceap class c4 higher 644 25 limbs prior history vte 56 trend improvement clinical parameters vcss vas pain edema grade performance stenting upto 90 ulcer healing rate noted stenting total 24 limbs required form reintervention 53 initial stent placementconclusion venous intervention form endovenous stenting associated improvement clinical parameters patients central neuromuscular disorders however patients counselled relatively higher rate reinterventions may needed correct residual recurrent symptomspmid34695594 doi101016 jjvsv202110010,0.0
demographic clinical factors associated frequent shortnotice cancellations veterans multiple sclerosis disease modifying therapies arch phys med rehabil 2021 oct 22s00039993 21 014994 doi 101016 japmr202110004 online ahead printabstractobjectives 1 identify rate shortnotice cancelled appointments large national sample persons multiple sclerosis ms 2 examine demographic clinical factors associated frequent cancellationsdesign retrospective crosssectional cohort using electronic health recordssetting veterans health administration va participants veterans ms n 3 742 part va ms center excellence data repository 1 least one outpatient appointment va 2013 2 alive 2015 3 prescribed disease modifying therapy dmt interventions applicablemain outcome measures frequent shortnotice cancellations defined 20 scheduled appointments cancelled less 24hour notification 24month period threshold based definition 80 suboptimal treatment adherence several demographics clinical variables examined potential explanatory factorsresults approximately 75 n 2 827 least one shortnotice cancellation 3 n 117 categorized frequent cancellers odds frequent cancellations greater women 181 p 004 among 1844 yearolds 277 p 004 4564 yearolds 249 p 003 compared 65+ yearolds odds lower among persons lived 25 miles away 058 p 043 compared persons lived 75 miles away least one er visit 055 p 012 conclusions shortnotice cancellations common persons ms although 20 findings highlight greater risk frequent cancellation disruptions care additional research needed results provide insights clinics may approach handling frequent shortnotice cancellations among persons mspmid34695387 doi101016 japmr202110004,0.0
nucleic acids novel therapeutic modalities address multiple sclerosis onset progression cell mol neurobiol 2021 oct 25 doi 101007 s10571021011584 online ahead printabstractthe issue treating multiple sclerosis ms begins diseasemodifying treatments dmts may cause lymphopenia dyspnea many adverse effects consequently identification evaluation alternative treatments crucial monitoring longterm outcomes hopefully moving toward personalized approaches can translated clinical treatments article focused novel therapeutic modalities alter interaction cellular constituents contributing ms onset progression furthermore studies performed evaluate optimize drugs efficacy particularly show limitations strengths also presented preclinical trials novel approaches multiple sclerosis treatment provide promising prospects cure disease pinpoint precision considering fact single treatment effective enough cover aspects ms treatment additional researches therapies need developed future since pathophysiology ms resembles jigsaw puzzle researchers need put host pieces together create promising window towards ms treatment thus combination therapy encompassing modules highly likely succeed dealing disease use different therapeutic approaches reinduce selftolerance autoreactive cells contributing ms pathogenesis presented combination therapy using tools may help deal clinical disabilities symptoms disease futurepmid34694513 doi101007 s10571021011584,0.0
ddimer elevation first alemtuzumab administration multiple sclerosis patient case report acta neurol belg 2021 oct 24 doi 101007 s1376002101822y online ahead printno abstractpmid34693511 doi101007 s1376002101822y,0.0
myelinassociated oligodendrocyte basic protein rs616147 polymorphism risk factor parkinson#39 s disease acta neurol scand 2021 oct 25 doi 101111 ane13538 online ahead printabstractbackground rs616147 polymorphism myelinassociated oligodendrocyte basic protein mobp gene locus associated amyotrophic lateral sclerosis als als parkinsons disease pd two common neurodegenerative disorders share features regarding etiology pathophysiology genetic backgrounds mobp rs616147 polymorphism associated als little known role pdobjective assess role mobp rs616147 pd riskmethods casecontrol comparison study consists 358 pdaffected cases 358 controls neurology clinic university hospital larissa university thessaly faculty medicine greece diagnosis pd made specialist neurologist according uk parkinsons disease society brain banks clinical criteria participants genotyped mobp rs616147 furthermore order validate results genotyped 327 patients alzheimers disease ad mobp rs616147 compared control groupresults according univariate analysis significant association rs616147 pd dominant 95 ci 070 052094 p 018 overdominant 95 ci 068 050092 p 011 codominant g vs g g 95 ci 066 048091 p 035 modes inheritance contrast association mobp rs616147 polymorphism adconclusions provide preliminary results associating mobp rs616147 genetic variant pdpmid34694630 doi101111 ane13538,1.0
incidence paediatric multiple sclerosis acquired demyelinating syndromes 10year followup surveillance study dev med child neurol 2021 oct 24 doi 101111 dmcn15098 online ahead printabstractaim describe 10year followup children 16y acquired demyelinating syndromes ads ukwide prospective surveillance studymethod diagnoses retrieved patients records via patients paediatric adult neurologist using questionnaire demyelinating phenotypes followup classified expert review panelresults twentyfour 125 192 children 64 males 61 females median age 10y range 1y 4mo15y 11mo identified original study diagnosed multiple sclerosis incidence 204 million children year 23 24 fulfilled 2017 mcdonald criteria onset aquaporin4antibody neuromyelitis optica spectrum disorders diagnosed three 24 026 million children year relapsing myelin oligodendrocyte glycoprotein antibodyassociated disease five 4 043 million children year three 125 seronegative patients relapsed 85 125 68 remained monophasic 10 years five 125 patients 4 originally diagnosed ads reclassified followup three children diagnosed initially acute disseminated encephalomyelitis subsequently diagnosed acute necrotising encephalopathy ranbinding protein 2 mutation primary haemophagocytic lymphohistiocytosis munc 134 gene inversion antinmethyldaspartate receptor encephalitis one child initially diagnosed optic neuritis later diagnosed vitamin b12 deficiency one presenting transverse myelitis subsequently diagnosed sjgren syndromeinterpretation majority ads presentations children monophasic even 10year followup given implications treatment strategies multiple sclerosis central nervous system autoantibody mimics warrant extensive investigationpmid34693523 doi101111 dmcn15098,1.0
cerebellar pathology disability worsening relapsingremitting multiple sclerosis retrospective analysis combirx trial eur j neurol 2021 oct 25 doi 101111 ene15157 online ahead printabstractbackground cerebellar damage valuable predictor disability particularly progressive multiple sclerosis ms clear equally useful predictor motor disability worsening relapsingremitting phenotypemethods cerebellar lesion loads volumes estimated baseline mri scan combirx trial n838 relationship cerebellar damage time disability worsening confirmed disability progressioncdp timed 25 foot walk testt25fwt 9hole peg test9hpt worsening tested stagewise stepwise cox proportionalhazards models accounting demographics supratentorial damageresults shorter time 9hpt worsening associated higher baseline edss hr 1408 p00042 higher volume supratentorial cerebellar t2 lesions hr 1005 p00196 hr 2211 p00002 respectively shorter time t25fwt worsening associated higher baseline edss hr 1232 p00006 shorter time cdp associated older age hr 1026 p00010 lower baseline edss hr 0428 p00001 higher volume supratentorial t2 lesions hr 1024 p00001 conclusion among explored outcomes single timepoint evaluation cerebellar damage allows prediction manual dexterity worsening clinical studies selection imaging biomarkers informed outcome interestpmid34695274 doi101111 ene15157,0.0
noninvasive individualized cortical modulation using transcranial rotating permanent magnet stimulator voiding dysfunction women multiple sclerosis pilot trial j urol 2021 oct 25101097ju0000000000002297 doi 101097 ju0000000000002297 online ahead printabstractbackground voiding dysfunction vd leading urinary retention common neurogenic lower urinary tract symptom multiple sclerosis ms patients currently effective management ms patients vd catheterization transcranial rotating permanent magnet stimulator trpms noninvasive portable multifocal neuromodulator simultaneously modulates multiple cortical regions strength functional connections pilot trial clinicaltrialsgov identifier nct03574610 investigated safety therapeutic effects trpms modulating brain regions interest roi engaged voiding initiation improve vd ms womenmethods ten ms women vd postvoid residual bladder capacity pvr bc 40 lower 10th percentile liverpool nomogram underwent concurrent functional magnetic resonance imaging urodynamic study fmri uds three cycles bladder filling emptying baseline posttreatment predetermined rois activations voiding initiation identified patients baseline fmri uds scans corresponding microstimulators placement patients received ten consecutive 40minute treatment sessions brain activation group analysis noninstrumented uroflow validated questionnaires compared baseline posttreatmentresults treatmentrelated adverse effect reported posttreatment patients showed significantly increased activation regions known involved voiding initiation healthy subjects pvr bc significantly decreased significant improvement bladder emptying symptoms reported patients via validated questionnairesconclusion neuroimaging clinical data suggested trpms effectively safely modulated brain regions involved voiding phase micturition cycle leading clinical improvements bladder emptying ms patientspmid34694911 doi101097 ju0000000000002297,0.0
effects robotassisted gait training patients multiple sclerosis singleblinded randomized controlled study j phys med rehabil 2021 oct 20 doi 101097 phm0000000000001913 online ahead printabstractobjective study aims evaluate compare effects conventional robotassisted gait training ragt programs fatigue mood quality life patients multiple sclerosis ms fatiguemethods singleblinded randomized controlled study thirtyseven patients ms randomized two groups ragt n 18 conventional gait training cgt n 19 ragt group gait training robogait cgt group received conventional physiotherapistassisted gait training outcome measures fatigue severity scale fss hospital anxiety depression scale hads multiple sclerosis quality life54 msqol54 extended disability status scale edss functional ambulation category fac berg balance test bbt six minute walk test 6mwt results baseline demographic clinic functional data similar groups showed improvements fss hadsdepression msqol bbt 6mwt scores treatment ragt group showed improvement hadsanxiety score ragt group better fss hads scoresconclusion combination standard rehabilitation program ragt cgt effective ms however ragt superior effects terms fatigue depression anxiety therefore may preferred ms patients exhibit prominent symptoms fatigue depression anxietypmid34686632 doi101097 phm0000000000001913,1.0
covid19 vaccine response people multiple sclerosis ann neurol 2021 oct 22 doi 101002 ana26251 online ahead printabstractobjective investigate effect disease modifying therapies immune response sarscov2 vaccines people multiple sclerosismethods 473 people multiple sclerosis provided one dried blood spot samples information covid19 vaccine history medical drug history extracted questionnaires medical records dried blood spots eluted tested antibodies sarscov2 antibody titres partitioned tertiles people disease modifying therapy reference calculated odds ratio seroconversion univariate logistic regression compared quantitative vaccine response kruskal wallis following sarscov2 vaccine according disease modifying therapy used regression modelling explore effect vaccine timing treatment duration age vaccine type lymphocyte count vaccine responseresults compared disease modifying therapy use anticd20 monoclonal antibodies odds ratio 003 95 confidence interval 001006 p0001 fingolimod odds ratio 004 95 confidence interval 001012 associated lower seroconversion following sarscov2 vaccine drugs differ significantly untreated cohort time since last anticd20 treatment total time treatment significantly associated response vaccination vaccine type significantly predicted seroconversion anticd20 medications preliminary data cellular tcell immunity showed 40 seronegative subjects measurable antisarscov2 t cell responsesinterpretation disease modifying therapies convey risk attenuated serological response sarscov2 vaccination people ms provide recommendations practical management patient group article protected copyright rights reservedpmid34687063 doi101002 ana26251,0.0
colored filters enhancing visual evoked potential vep response multiple sclerosis j optom 2021 oct 19s18884296 21 000637 doi 101016 joptom202109005 online ahead printno abstractpmid34686477 doi101016 joptom202109005,0.0
relapsingremitting secondaryprogressive mspatients differ decoding others emotions eyes eur j neurol 2021 oct 22 doi 101111 ene15155 online ahead printabstractbackground difficulties emotion processing social cognition identified ms patients potential impact adaptation social environmentobjective aimed explore neural correlates emotion recognition ms possible differences relapsingremitting rrms secondaryprogressive spms patients reading mind eyes test rmet method total 43 ms patients 27 rrms 16 spms 25 matched healthy controls hc underwent clinical assessments rmet highresolution t1weighted mri scan 3t number correct answers rmet compared groups t1weighted volumes processed according optimized voxelbased morphometry vbm protocol obtain grey matter gm maps voxelwise analyses run assess potential associations rmet performance regional gm volumesresults taken altogether ms patients reported significantly lower performance rmet compared hc dividing patients rrms spms latter group found perform significantly worse hc rmet vbm analysis revealed significant association rmet scores gm volumes several cortical temporoparietooccipital cortex subcortical hippocampus parahippocampus basal ganglia brain regions cerebellum spms patients onlyconclusions results suggest addition clinical differences rrms spms ability recognize others emotional states may interest spms significantly rrms patients supported behavioral mri datapmid34687120 doi101111 ene15155,0.0
efficacy highintensity aerobic exercise common multiple sclerosis symptoms acta neurol scand 2021 oct 22 doi 101111 ane13540 online ahead printabstractobjectives fatigue walking impairment disabling symptoms multiple sclerosis ms investigated effects progressive aerobic exercise pae fatigue walking cardiorespiratory fitness vo2 max quality life people ms pwms materials methods randomized controlled trial 11 ratio stratified sex 24week crossover followup intentiontotreat analysis allocation exercise 24 weeks pae followed selfguided physical activity waitlist 24 weeks habitual lifestyle followed pae group pae comprised two supervised sessions per week 3060 min 6595 maximum heart rate fatigue impact modified fatigue impact scale mfis severity fatigue severity scale fss walking ability 12item ms walking scale msws12 capacity sixminute walk test 6mwt six spot step test ssst quality life short form 36 health survey sf36 vo2 max measured baseline 24 weeks 48 weeksresults eightysix pwms enrolled following pae betweengroup differences showed reductions mfistotal 53 95 ci 109 04 point estimate clinical relevance mfisphysical subscore 28 56 01 mfispsychosocial subscore 09 16 02 increase vo2 max +35 ml o2 min kg 20 51 msws12 59 119 02 6mwt +14 m 5 33 differences suggested potential small walking improvements changes observed fss ssst sf36conclusions representative sample pwms pae induced clinically relevant reduction fatigue impact whereas small effects seen walking quality life respectively results need confirmation future trial due study limitationspmid34687036 doi101111 ane13540,0.0
humoral immunity sarscov2 mrna vaccination multiple sclerosis relevance time since last rituximab infusion first experience sporadic revaccinations j neurol neurosurg psychiatry 2021 oct 20jnnp2021327612 doi 101136 jnnp2021327612 online ahead printabstractintroduction effect diseasemodifying therapies dmt vaccine responses largely unknown understanding development protective immunity paramount importance fight covid19 pandemicobjective characterise humoral immunity mrnacovid19 vaccination people multiple sclerosis pwms methods pwms norway fully vaccinated sarscov2 invited national screening study humoral immunity assessed measuring antisarscov2 spike rbd igg response 312 weeks full vaccination compared healthy subjectsresults 528 pwms 627 healthy subjects included reduced humoral immunity antisarscov2 igg 70 arbitrary units present 82 80 pwms treated fingolimod rituximab respectively patients treated dmt showed similar rates healthy subjects untreated pwms found significant correlation time since last rituximab dose development humoral immunity revaccination two seronegative patients induced weak antibody responseconclusions patients treated fingolimod rituximab informed risk reduced humoral immunity vaccinations timed carefully rituximab patients results identify need studies regarding durability vaccine responses role cellular immunity revaccinationspmid34670844 doi101136 jnnp2021327612,0.0
association serum prolactin levels neurodegenerative diseases systematic review metaanalysis neuroimmunomodulation 2021 oct 20112 doi 101159 000519552 online ahead printabstractintroduction prolactin prl exerts inflammatory antiinflammatory properties also thought play important role pathogenesis neurodegenerative diseases nds however serum prl levels patients nds inconsistent research literatureobjective aimed assess serum prl levels patients ndsmethods electronic databases including medline embase cochrane library database clinicaltrialsgov web science google scholar reference lists articles searched december 31 2020 pooled standard mean difference smd 95 confidence interval ci calculated fixedeffect randomeffect model analysisresults total 36 comparisons 29 studies 3 rcts 26 case controls focusing nds including parkinsons disease alzheimers disease huntingtons disease hd multiple sclerosis ms epilepsy reported metaanalysis showed statistically significant difference serum prl levels patients nds healthy controls smd 040 95 ci 016 096 p 016 subgroup analysis showed serum prl levels patients hd ms higher healthy controls furthermore patients nds aged 45 years higher serum prl levels smd 097 95 ci 016178 p 0018 healthy controls high serum prl levels found subgroups microenzymatic method asia americasconclusions metaanalysis showed serum prl levels patients hd ms significantly higher healthy controls serum prl levels associated age region detection method larger sample studies using uniform detection methods necessary confirm resultspmid34670217 doi101159 000519552,0.0
preclinical pharmacology toxicology evaluation anticd52 monoclonal antibody produced perfusion fermentation process j ind microbiol biotechnol 2021 oct 20kuab078 doi 101093 jimb kuab078 online ahead printabstractanticd52 monoclonal antibody employed treatment chronic lymphoblastic leukemia multiple sclerosis previously developed perfusion process produce biosimilar mab named mabth series quality assessments conducted fields structural identification purity analysis activity measurement quality researches report laid emphasis preclinical pharmacology toxicology evaluation mabth characterized biological pharmacological toxicological properties comparison original drug alemtuzumab binding activity immune dependent toxicity vitro activity evaluated severer immune deficient mice transplanted human leukemia cell line also used vivo pharmacological model fourweek repeated dosing study cynomolgus monkeys conducted evaluate safety differences results demonstrated mabth anticd52 antibody generated perfusion process high similarity vitro vivo activities compared alemtuzumab relevant preclinical models results supported biosimilar candidate clinical evaluationpmid34669957 doi101093 jimb kuab078,0.0
product review mabs alemtuzumab ocrelizumab treatment multiple sclerosis hum vaccin immunother 2021 oct 20118 doi 101080 2164551520211969850 online ahead printabstracttraditionally management active relapsing remitting ms based socalled maintenance therapy characterized continuous treatment particular disease modifying therapy dmt return disease activity drug discontinued another approach characterized short treatment course dmt hypothesized act immune reconstitution therapy irt potential protect relapses years short course treatment introduction monoclonal antibodies treatment ms revolutionized ms treatment last decade however given increasingly complex landscape dmts approved ms people ms neurologists constantly faced question dmt appropriate given patient question still answer product review will discuss first dmt acts irt anticd52 monoclonal antibody alemtuzumab anti cd20 monoclonal antibody ocrelizumab potential act irt administered continuously special emphasis will given safety context covid19 pandemics vaccination strategiespmid34668842 doi101080 2164551520211969850,0.0
neurological autoimmune diseases following vaccinations sarscov2 case series eur j neurol 2021 oct 19 doi 101111 ene15147 online ahead printabstractbackground populationbased studies suggest sarscov2 vaccines may trigger immunemediated thrombotic thrombocytopenia vitt raising concerns autoimmune responses aimed characterize neurological autoimmunity sarscov2 vaccinationsmethods singlecenter prospective case study report patients neurological autoimmunity temporal association 6 weeks sarscov2 vaccinations without triggers clinical laboratory imaging data collected median followup 49 daysresults study period 232 603 inhabitants main catchment area hospital rheinneckarkreis county received sarscov2 vaccinations identified 21 cases new onset n17 flares n4 diagnosed median 11 days range 323 following sarscov2 vaccinations bnt162b2 n12 chadox1 n8 mrna1273 n1 cases included vitt cerebral venous sinus thrombosis n3 central nervous system demyelinating diseases n8 inflammatory peripheral neuropathies n4 myositis n3 myasthenia n1 limbic encephalitis n1 giant cell arteritis n1 patients predominantly female ratio 321 median age diagnosis 50 years range 2286 therapy included administration steroids n15 intravenous immunoglobulins patients guillainbarr syndrome vitt n4 plasma exchange cases unresponsive steroids n3 anticoagulation vitt outcomes favorable partial complete remissions achieved 71 24 respectively two patients received second vaccination without aggravation autoimmune symptoms lowdose immunosuppressantsconclusions study characterize various neurological autoimmune disorders encountered following sarscov2 vaccinations given assumed low incidence mostly favorable outcome autoimmune reponses benefits vaccinations outweigh comparatively small riskspmid34668274 doi101111 ene15147,1.0
barriers leading increased disability neurologically challenged populations covid19 pandemic scoping review disabil rehabil 2021 oct 19114 doi 101080 0963828820211986747 online ahead printabstractpurpose objective scoping review get overview barriers emerging across globe pandemic likely increase level preexisting disability status neurologically challenged populationsmethods database searches pubmed medline cinahl proquest ovid scopus web science updated december 2020 conducted articles identified challenges barriers neurorehabilitation impact disability status health care services included fulltext articles limited english language restrictions study design included data synthesized based recurrent themes identifiedresults thirtyseven studies included review neurological populations considered stroke multiple sclerosis amyotrophic lateral sclerosis parkinsons disease autism developmental disabilities required neurosurgical care barriers grouped categories increased disease risk complications delayed restricted access neurorehabilitation limited hospital access telerehabilitation limitations shutdown special centers aidconclusions covid19 pandemic given rise barriers affect almost every aspect healthcare rehabilitation neurologically challenged populations prompting increase disability level can assist policymakers designing mitigation strategies minimize detrimental effects vulnerable populationimplications rehabilitationpandemic led worsening existing motor nonmotor symptoms need monitored assessed managed medically rehabilitation neurologically challenged populationsnotable decline cognition physical activity neurologically challenged populations needs assessed efforts reverse outcomes attemptedrehabilitation services hospital care centers aid need made accessible neurologically challenged populations covid19 precautionary measurestelemedicine telerehabilitation need upgraded enhance face face like interactions tracking progressive diseasepmid34666575 doi101080 0963828820211986747,0.0
candidate gene study reveals association variant srp55 splicing factor gene systemic sclerosis clin exp rheumatol 2021 oct 19 online ahead printabstractobjectives examine possible implication mrnabinding protein serine arginine protein 55 srp55 also known srsf6 rs2235611 single nucleotide polymorphism snp genetic predisposition systemic sclerosis ssc susceptibility clinical phenotypemethods total population 872 white italian individuals 414 ssc patients 458 controls studied ssc patients assessed limited diffuse cutaneous subsets presence autoantibodies interstitial lung disease ild nailfold videocapillaroscopy nvc abnormalities srp55 rs2235611 snp genotyped taqman realtime pcrresults srp55 rs2235611 genotype distribution allele frequency similar ssc healthy controls though trend toward significance observed genotype distribution p007 srp55 rs2235611 aa genotype significantly influenced predisposition ssc p 003 srp55 rs2235611 minor allele aa genotype showed significant risk association susceptibility sscrelated ild allele p0046 aa genotype p0007 significant association aa genotype ssc late nvc pattern also found p0006 bonferroni correction multiple comparisons risk association srp55 rs2235611 aa genotype sscrelated ild late nvc pattern remained significant padj0049 padj0042 respectively conclusions srp55 rs2235611 aa genotype significantly influences susceptibility ssc specifically associates presence sscrelated ild late nvc pattern indepth studies srp55 gene locus will hopefully contribute extend knowledge genetic predisposition major sscrelated manifestations pulmonary fibrosis peripheral microvasculopathypmid34665708,0.0
serinethreonine kinase inhibition antifibrotic therapy tgf rock inhibitors rheumatology oxford 2021 oct 19keab762 doi 101093 rheumatology keab762 online ahead printabstractserinethreonine kinases mediate phosphorylation intracellular protein targets transferring phosphorus group atp molecule specific amino acid residues within target proteins serinethreonine kinases regulate multiple key cellular functions large group kinases transforming growth factor beta tgf serinethreonine activity receptors rho kinase rock play important role development maintenance fibrosis various human diseases including systemic sclerosis recent years multiple drugs targeting inhibiting kinases developed opening possibility becoming potential antifibrotic agents clinical value treating fibrotic diseases review analyzes contribution tgf rockmediated serinethreonine kinase molecular pathways development maintenance pathological fibrosis potential clinical use inhibitionpmid34664623 doi101093 rheumatology keab762,0.0
rim lesions demonstrated early relapsingremitting multiple sclerosis using 3 tbased susceptibilityweighted imaging multiinstitutional setting neuroradiology 2021 oct 19 doi 101007 s0023402102768x online ahead printabstractpurpose rim lesions characterised paramagnetic rim susceptibilitybased mri suggested reflect chronic inflammatory demyelination multiple sclerosis ms patients assess susceptibilityweighted imaging swi prevalence longitudinal volume evolution clinical associations rim lesions subjects early relapsingremitting ms rrms methods subjects n 44 recently diagnosed rrms underwent 3 t mri baseline m0 1 year m12 part multicentre study swi acquired m12 using 3d segmented gradientecho echoplanar imaging sequence rim lesions identified swi manually segmented flair images time points volumetric analysisresults twelve subjects 27 least one rim lesion m12 linear mixedeffects model subject random factor revealed mixed evidence difference longitudinal volume change rim lesions nonrim lesions p 00350 p 00556 subjects without rim lesions respectively 25 rim lesions identified showed t1weighted hypointense signal subjects without rim lesions differ significantly respect age disease duration clinical measures disability p 005 conclusion demonstrate rim lesions detectable earlystage rrms 3 t mri across multiple centres although relationship lesion enlargement equivocal small cohort identification swi rims subjective agreed criteria defining rim lesions validation biomarker chronic inflammation required translation swi routine ms clinical practicepmid34664112 doi101007 s0023402102768x,1.0
simultaneous modulation nlrp3 inflammasome nrf2#x2f pathway rescues thioacetamideinduced hepatic damage mice role oxidative stress inflammation inflammation 2021 oct 18 doi 101007 s10753021015713 online ahead printabstractchronic tissue injury resulting fibrosis multiple organs responsible onethird death globally liver fibrosis common pathway condition involved chronic liver diseases thioacetamide taa hepatotoxicant used induce hepatic fibrosis antidiabetic drug glibenclamide glb possesses antiinflammatory properties inhibits nacht lrr pyd domainscontaining protein 3 nlrp3 inflammasome activation dimethyl fumarate dmf multiple sclerosis drug activates nuclear factor erythroid 2related factor 2 nrf2 antioxidant response element pathway maintains antioxidant status cell present study designed investigate role nlrp3 inflammasome nrf2 pathway taainduced hepatotoxicity liver fibrosis ii mechanism involved glb dmf mediated hepatoprotection taainduced hepatotoxicity iii additional synergistic hepatoprotective effect combination treatment nlrp3 inhibition + nrf2 activation glb + dmf mcc950 + 4oi reverse ameliorate experimental liver fibrosis completely taa administered intraperitoneally mice seven consecutive weeks treatments glb dmf glb + dmf mcc950 4oi mcc950 + 4oi provided last three consecutive weeks intervention glb dmf glb + dmf mcc950 4oi mcc950 + 4oi significantly protected taainduced oxidative stress inflammatory conditions improving biochemical histological immunoexpression changes mice glb dmf glb + dmf intervention exhibited better protective effect compared mcc950 4oi mcc950 + 4oi revealed specific inhibitor activator possesses nlrp3 inflammasome inhibitory nrf2 activatory properties contrast clinical drug glb dmf several beneficial effects independent nlrp3 inhibition nrf2 activationpmid34664134 doi101007 s10753021015713,0.0
quality life individuals newly diagnosed multiple sclerosis clinically isolated syndrome j neurol 2021 oct 19 doi 101007 s0041502110842w online ahead printabstractbackground little known quality life qol time multiple sclerosis ms clinically isolated syndrome cis diagnosis evolves critical adjustment period immediately following new diagnosisobjectives 1 describe qol trajectory first year postms cis diagnosis 2 examine associations demographic biopsychosocial factors qol baseline evolves first year postms cis diagnosismethods participants n 250 individuals newly diagnosed ms cis participants completed selfreport assessments qol demographics biopsychosocial factors 1 2 3 6 9 12 months postdiagnosis using validated measuresresults 1month postdiagnosis qol m 752 100 subsequent assessments revealing consistent ratings average modelling revealed small number variables predictive qol baseline change qol timeconclusion qol first year postms cis diagnosis average high stable subset modifiable factors across biopsychosocial spectrum associated baseline level qol change qol time stability qol suggests patients can assessed early diagnosis key variables predictive current future qolpmid34665331 doi101007 s0041502110842w,0.0
central vein sign multiple sclerosis lesions susceptibility relaxation optimization routine mri multiecho gradient echo sequence j neuroimaging 2021 oct 19 doi 101111 jon12938 online ahead printabstractbackground purpose white matter lesion central vein sign cvs emerging biomarker multiple sclerosis ms differential diagnosis currently cvs detected susceptibility weighted imaging swi suboptimal contrast developed imaging method called susceptibility relaxation optimization sro improve cvs visualizationmethods retrospective study ms patients mri june 2018 routine 3d multiecho gradient echo gre t2weighted fluidattenuated inversion recovery flair sequences sro swi images reconstructed gre data ms lesions identified flair image cvs detection rate image quality score cvs conspicuity range 03 central veintolesion contrast compared sro swi imagesresults 20 ms patients mean age 45 9 years 15 women sro significantly increased cvs detection rate compared swi 533 274 514 vs 329 169 514 p001 mcnemars test median image quality score sro 2 compared 1 swi p001 wilcoxon signedrank test median overall image quality score sro 7 compared 6 swi p 003 wilcoxon signedrank test central veintolesion contrast 012 012 sro compared 0031 0075 swi p001 ttest conclusions sro yields better central vein contrast increases cvs detection rate compared swipmid34664747 doi101111 jon12938,0.0
increasing role imaging differentiating ms nonms defining indeterminate borderline cases neurol neurochir pol 2021 oct 19 doi 105603 pjnnsa20210077 online ahead printabstractmultiple sclerosis ms heterogenous condition differences patients regarding disease presentation imaging features disease activity prognosis treatment responses following discovery new biomarkers concept ms evolved syndromes previously considered variants now recognised separate entities including aquaporin4 aqp4 antibody ab neuromyelits optica spectrum disorders nmosd myelin oligodendrocyte glycoprotein mog ab disease mogad line distinct pathology newly emerging conditions imaging characteristics dissimilar typical ms progress reclassifying demyelinating cns conditions highlighted challenge meaningful categorisation atypical presentations borders ms antibodynegative neuromyelitis opticalike syndromes tumefactive demyelinating lesions balos concentric sclerosis review discuss increasing role imaging distinguishing ms nonms cns inflammatory demyelinating conditions defining undetermined borderline cases progress relies better characterisation imaging features conditions conventional imaging terms appearance location well implementation novel image acquisition postprocessing techniques allowing indepth lesion assessment including presence central vein sign paramagnetic rimpmid34664709 doi105603 pjnnsa20210077,1.0
neurotoxicity pesticides context cns chronic diseases int j environ health res 2021 oct 19138 doi 101080 0960312320211987396 online ahead printabstractfollowing introduction application pesticides human life always along health concerns acute poisoning chronic toxicities neurotoxicity pesticides chronic exposures known one important human health problems chemicals act interacting elements nervous system pesticideinduced neurotoxicity can defined different categories neurological disorders including neurodegenerative alzheimer parkinson amyotrophic lateral sclerosis multiple sclerosis neurodevelopmental attention deficit hyperactivity disorder autism spectrum disorders developmental delay intellectual disability neurobehavioral neuropsychiatric depression suicide attempt anxiety insomnia cognitive impairment disorders among debilitating human health problems review neurotoxicity pesticides mentioned categories subcategories neurological diseases systematically presented relation different route exposures including general occupational environmental prenatal postnatal paternalpmid34663153 doi101080 0960312320211987396,0.0
shortchain fatty acid pregnancy multiple sclerosis prospective cohort study eur j neurol 2021 oct 18 doi 101111 ene15150 online ahead printabstractbackground shortchain fatty acids scfas can pro antiinflammatory properties relationship multiple sclerosis ms relapses pregnancy remains unknown study aimed explore scfa profiles ms patients pregnancy assess association appearance relapses pregnancy postpartummethods prospectively included 53 pregnant ms patients 21 healthy control women patients evaluated pregnancy puerperium scfas measured liquid chromatographymass spectrometryresults sixteen patients 32 relapses pregnancy puerperium 37 68 ms patients showed significant increases acetate levels pregnancy postpartum period compared nonms women however propionate butyrate values associated disease activity values higher nonrelapsing patients remained similar control group relapsing patients variable best identified active patients propionate acetate ratio ratios 036 first trimester associated higher inflammatory activity odds ratio 165 confidence interval ci 1022394 p 001 nonrelapsing patients showed values 036 similar healthy pregnant womenconclusions low propionate acetate ratio values first trimester gestation identified ms patients risk relapses pregnancy postpartum periodpmid34662474 doi101111 ene15150,0.0
birthweight subsequent risk thyroid autoimmune conditions postmenopausal women j dev orig health dis 2021 oct 1818 doi 101017 s204017442100057x online ahead printabstractthe objective study determine association birthweight risk thyroid autoimmune conditions large sample postmenopausal women baseline data womens health initiative n 80 806 used examine associations birthweight category 6 lbs 67 lbs 15 oz 89 lbs 15 oz 10 lbs prevalent thyroid underactive overactive thyroid goiter autoimmune lupus rheumatoid arthritis ra multiple sclerosis ulcerative colitis crohns disease conditions followup questionnaire data used examine associations birthweight incident underactive overactive thyroid lupus ra logistic cox proportional hazards regression models used estimate crude adjusted odds hazards ratios hr respectively overall women born weighing 10 lbs increased risk underactive thyroid 114 95 ci 102 128 incident lupus hr 151 95 ci 112 203 decreased risk overactive thyroid 067 95 ci 050 092 compared women born weighing 6799 lbs adjustment adult bmi demographic variables lifestyle factors women born weighing 6 lbs increased risk underactive thyroid 113 95 ci 104 122 birthweight associated thyroid autoimmune disorders high birthweight associated laterlife thyroid autoimmune conditions low birthweight associated underactive thyroid preconception prenatal interventions aimed reducing risk high low birthweights may reduce burden laterlife thyroid autoimmune conditionspmid34658316 doi101017 s204017442100057x,0.0
brief international cognitive assessment multiple sclerosis scores associated cortical thickness specific cortical areas relapsingremitting patients rev neurol paris 2021 oct 14s00353787 21 007025 doi 101016 jneurol202106014 online ahead printabstractbackground cognitive impairment frequent disabling multiple sclerosis ms brief international cognitive assessment ms bicams recent short battery usable clinical practice cognitive evaluation ms patientsobjective find cortical areas brain volumes magnetic resonance imaging mri structural sequences associated bicams scores msmethods crosssectional singlecenter study nct03656055 september 4 2018 96 relapsing remittingms patients natalizumab without recent clinical radiological inflammation included patients underwent brain mri three bicams tests evaluating information processing speed sdmt visuospatial memory bvmtr verbal memory fvlt results cortical thickness left frontal superior right precentral gyri associated bvmtr scores whereas cortical thickness left brocas area right superior temporal gyrus associated fvlt scores observed associations white matter inflammatory lesions connected cortical regions bicams subscoresconclusions bicams scores associated specific cortical areas cognitive domain matching known functions cortical area specific cognitive impairments ms may associated specific cortical regions influenced white matter inflammatory lesions demographical parameters age sex education level pmid34657733 doi101016 jneurol202106014,0.0
current status drug repositioning hematology expert rev hematol 2021 oct 16 doi 101080 1747408620211995348 online ahead printabstractintroduction drug repositioning dr defined determining new therapeutic applications existing drugs approach advantageous de novo drug discovery accelerating clinical development terms lower costs shortened development period wellknown action mechanism feasible dosage acceptable safety profileareas covered work aimed reviewing agents successful dr hematologyexpert opinion thalidomide plerixafor successfully repositioned treating multiple myeloma harvesting peripheral blood stem cells respectively former originally developed sedative latter antihiv drug currently feasibility repositioning various agents explored eg antiinfluenza virus drug oseltamivir primary immune thrombocytopenia antihiv drug abacavir adult tcell leukemia macrolide antibiotic clarithromycin multiple myeloma furthermore bosutinib chronic myeloid leukemia antiplatelet drug cilostazol suggested clinical benefits management amyotrophic lateral sclerosis ischemic stroke respectively promote dr effective application artificial intelligence stem cell models comprehensive database construction shared academia pharmaceutical companies suitable handling drug patents wide cooperation area specialty warrantedpmid34657533 doi101080 1747408620211995348,0.0
cerebellar contributions motor impairments people multiple sclerosis cerebellum 2021 oct 17 doi 101007 s12311021013366 online ahead printabstractalthough charcot characterized classic cerebellar symptoms people multiple sclerosis pwms 1877 impact cerebellar dysfunction ms symptoms predominately evaluated last two decades recent studies clearly demonstrated association cerebellar pathology including atrophy reduced fractional anisotropy peduncles motor impairments reduced gait velocity time complete walking tasks however future studies using novel imaging techniques needed elucidate potential pathophysiology associated disability pwms additionally future studies required determine effective treatments motor impairments pwms including specific type duration exercise interventions potential means amplify effects transcranial direct current stimulation tdcs minireview critically discusses distinct role cerebellar dysfunction motor impairments pwms potential treatments directions future studiespmid34657272 doi101007 s12311021013366,0.0
editorial quot improved assessment longitudinal spinal cord atrophy multiple sclerosis using registrationbased approach relevance clinical studiesquot j magn reson imaging 2021 oct 15 doi 101002 jmri27958 online ahead printno abstractpmid34655127 doi101002 jmri27958,0.0
understanding managing autonomic dysfunction patients multiple sclerosis expert rev neurother 2021 oct 15 doi 101080 1473717520211994856 online ahead printabstractintroduction multiple sclerosis ms chronic demyelinating immune mediated disease central nervous system autonomic dysfunction ad frequently present persons ms pwms increases disease duration progressionareas covered cardiovascular genitourinary sudomotor autonomic dysfunction pwms reviewed managing disorders addressedexpert opinion ad pwms can manifest myriad symptoms including cardiovascular urogenital sweating disorders symptoms can significantly impact quality life pwms poor tolerance upright position difficulties sexual function low endurance physical activity especially warm environments health professionals involved care pwms possess basic knowledge function autonomic nervous system informed way disorders autonomic function may manifest pwms order provide proper carepmid34654355 doi101080 1473717520211994856,1.0
effect bdnf val66met polymorphism hippocampal subfields multiple sclerosis patients mol psychiatry 2021 oct 14 doi 101038 s41380021013451 online ahead printabstractbrainderived neurotrophic factor bdnf val66met polymorphism shown strongly affect bdnf function role modulating gray matter damage multiple sclerosis ms patients still clear given bdnf relevance hippocampus aimed explore bdnf val66met polymorphism effect hippocampal subfield volumes role cognitive functioning ms patients using 3t scanner obtained dualecho 3dt1weighted sequences 50 ms patients 15 healthy controls hc consecutively enrolled ms patients also underwent genotype analysis bdnf neurological neuropsychological evaluation hippocampal subfields segmented using freesurfer bdnf val66met polymorphism found 22 ms patients 44 compared hc ms patients lower volume bilateral hippocampusamygdala transition area hata cornus ammonis ca 1 granule cell layer dentate gyrus gcldg ca4 ca3 left hippocampal head molecular layer ml left hippocampal body presubiculum right hippocampal body right fimbria compared bdnf val66val val66met ms patients higher volume bilateral hippocampal tail ca1 ml ca3 ca4 gcldg left hippocampal head ca1 ml ca3 left hippocampal body left hata presubiculum right hippocampal head ms patients higher lesion burden associated lower volume presubiculum right hippocampal body lower volume left hippocampal tail associated worse visuospatial memory performance lower volume left hippocampal head worse performance semantic fluency findings suggest bndf val66met polymorphism may protective role ms patients hippocampal atrophy cognitive impairment bdnf genotype might potential biomarker predicting cognitive prognosis interesting target study neuroprotective strategiespmid34650209 doi101038 s41380021013451,1.0
similarities differences multiple sclerosis type 1 diabetes diabetes metab res rev 2021 oct 14e3505 doi 101002 dmrr3505 online ahead printabstractmultiple sclerosis ms type 1 diabetes t1d chronic conditions result dysfunction immune system common root autoimmunity stimulates interest exploration similarities differences two diseases genetic susceptibility relevant creating substrate environmental factors act trigger aberrant immune response despite tcell mediated disorders strong involvement humoral arm immunomodulation mainstay ms management whereas hormone replacement therapy remains principal approach t1d t1d usually diagnosed children adolescents ms typical young adults difference implications disease progression treatment sarscov2 pandemic effect immunity may affect prevalence conditions well clinical manifestation article protected copyright rights reservedpmid34651395 doi101002 dmrr3505,0.0
cochlear implantation patient multiple sclerosis case report systematic review j laryngol otol 2021 oct 15118 doi 101017 s0022215121002917 online ahead printno abstractpmid34649636 doi101017 s0022215121002917,0.0
autopsy confirmed neuromyelitis optica spectrum disorder extensive brain white matter lesion optic neuritis intact spinal cord clinically mimicking secondary progressive multiple sclerosislike course intern med 2021 oct 12 doi 102169 internalmedicine763521 online ahead printabstracta 57yearold woman presented optic neuritis repeated clinical symptoms focal demyelination cerebral white matter brain stem 14 years end patients course clinical signs mimicked secondary progressive multiple sclerosis whether caused interferon administration neuromyelitis optica spectrum disorders nmosd combination otherswas unclear histopathological findings indicated etiology nmosd apparent plaque spinal cord specimens case suggests accurate clinical diagnosis requires serum antiaquaporin 4 antibody measurements well autopsy examinationpmid34645756 doi102169 internalmedicine763521,1.0
ocrelizumab treatment multiple sclerosis danish populationbased cohort study eur j neurol 2021 oct 13 doi 101111 ene15142 online ahead printabstractbackground realworld evidence regarding effectiveness safety ocrelizumab treatment multiple sclerosis ms limited aimed evaluate effectiveness safety ocrelizumab treatment ms realworld settingmethods conducted nationwide populationbased cohort study analyzed clinical mri data ms patients enrolled prospectively danish multiple sclerosis registry dmsr initiated ocrelizumab treatment january 2018 november 2020results total 1104 patients 857 relapsingremitting ms rrms 88 secondary progressive ms spms 55 primary progressive ms ppms included median followup period 13 years baseline mean age 414 years rrms group 445 years ppms group 503 years spms group median expanded disability status scale edss score 25 35 55 respectively rrms spms patients received previous diseasemodifying therapies 875 918 respectively whereas ppms patients mostly treatment nave 787 ocrelizumab initiation 93 patients experienced relapse 87 24week confirmed disability worsening conversely 167 showed 24week confirmed disability improvement 1 year treatment patients 945 free mri activity ocrelizumab generally well tolerated side effects reported 10 patients mostly consisting infusionrelated reactions infectionsconclusions show ms patients treated ocrelizumab clinically stabilized adverse event profile consistent experience pivotal clinical trialspmid34644452 doi101111 ene15142,0.0
infratentorial lesions multiple sclerosis patients intra interrater variability comparison fully automated segmentation using 3d convolutional neural networks eur radiol 2021 oct 13 doi 101007 s00330021083293 online ahead printabstractobjective automated quantification infratentorial multiple sclerosis lesions magnetic resonance imaging clinically relevant challenging overcome problems propose fully automated lesion segmentation algorithm using 3d convolutional neural networks cnns methods cnn trained flair image alone flair t1weighted images 1809 patients acquired 156 different scanners additional training using extra class infratentorial lesions implemented three experienced raters manually annotated three datasets 123 ms patients different scannersresults interrater sensitivity sen 80 supratentorial lesions 62 infratentorial lesions statistically significant difference interrater sen sen cnn respect raters supratentorial lesions cnn featured intrarater intrascanner sen 097 r1 090 r2 084 infratentorial lesion sen 093 r1 061 r2 073 conclusion performance cnn improved significantly infratentorial lesions specifically trained infratentorial lesions using t1 image additional input matches detection performance experienced raters furthermore infratentorial lesions cnn robust repeated scans experienced raterskey points 3d convolutional neural network trained mri data 1809 patients 156 different scanners quantification supratentorial infratentorial multiple sclerosis lesions interrater variability higher infratentorial lesions supratentorial lesions performance 3d convolutional neural network cnn improved significantly infratentorial lesions specifically trained infratentorial lesions using t1 image additional input detection performance cnn matches detection performance experienced raterspmid34643779 doi101007 s00330021083293,0.0
prognostic uncertainty multiple sclerosis concept analysis j clin nurs 2021 oct 12 doi 101111 jocn16069 online ahead printabstractaim report analysis concept prognostic uncertainty patients multiple sclerosis ms background complexity ambiguity involved diagnosis ms lead occurrence prognostic uncertainty among patients concept analysis presented analyses prognostic uncertainty means experiencing transition relapsingremitting multiple sclerosis secondary progressive multiple sclerosisdesign concept analysisdata sources pubmed ovid medline cumulative index nursing allied health literature databases searched literature published within last 10 years using combinations terms prognostic diagnostic uncertainty multiple sclerosis along archival referencingmethods walker avant method used analyse concept prognostic uncertainty patients msresults defining attributes identified provide additional context prognostic uncertainty illness uncertainty intolerance uncertainty progressive dwindling related contrary model borderline cases presented discuss application key attributes conceptconclusion limited data prognostic uncertainty multiple sclerosis however patients physicians express uncertainty understanding ones disease trajectory determining patient relapsingremitting multiple sclerosis entered secondary progressive multiple sclerosis disease course leading ineffective communication frustrationrelevance clinical practice genetics genomics potential provide prognostic factor addressing concept uncertainty relates persons multiple sclerosis moving beyond concept analysis case made nurse involvement genetic genomic research conduct trials translate apply findings clinical practice nursing curricula addressing uncertainty experienced afflicted chronic illnesses multiple sclerosispmid34643008 doi101111 jocn16069,0.0
stigma multiple sclerosis important role sense coherence relation quality life int j behav med 2021 oct 12 doi 101007 s12529021100300 online ahead printabstractbackground anticipated experienced stigma constitute important issues patients multiple sclerosis receiving adequate healthcare stigma likely associated lower quality life patients multiple sclerosis underlying mechanisms contributing factors unclearmethods conducted crosssectional survey among n 101 patients diagnosis multiple sclerosis german outpatient department patients completed questionnaires enacted selfstigma ssci8 sense coherence socl9 quality life musiqol age sex disease duration disability extent limitations edss cognition sdmt depression bdiii fatigue fsmc used covariates linear regression mediation modelsresults 573 patients ms reported experienced stigmatization due ms least fatigue b 0199 p 0001 enacted stigmatization experience b 0627 p 0010 sense coherence b 0654 p 0001 significant predictors quality life mediation analysis showed partial mediation association enacted stigma quality life patients sense coherence direct effect b 1042 t 4021 p 0001 indirect effect b 0773 ci 13510339 association selfstigma quality life fully mediated sense coherence b 1579 ci 29540669 conclusion patients multiple sclerosis affected stigma associated lower quality life sense coherence potentially important mediator stigma represents promising target refine existing stigma interventions improve quality life patientspmid34642890 doi101007 s12529021100300,0.0
evaluation aggregated time savings adopting fast brain mri techniques outpatient brain mri acad radiol 2021 oct 8s10766332 21 003196 doi 101016 jacra202107011 online ahead printabstractintroduction clinical validation studies demonstrated ability accelerated mri sequences decrease acquisition time motion artifact preserving image quality operational benefits however less explored report initial clinical experience implementing fast mri techniques outpatient brain imaging covid19 pandemicmethods aggregate acquisition times extracted medical record consecutive imaging examinations performed matched preimplementation 7 1 201912 31 2019 postimplementation periods 7 1 202012 31 2020 expected acquisition time reduction mri protocol calculated manual collection acquisition times conventional accelerated sequences performed pre postimplementation periods aggregate expected acquisition times compared five frequently performed brain mri protocols brain without contrast br brain without contrast br+ multiple sclerosis ms memory loss mml epilepsy epl results expected time reductions br br+ ms mml epl protocols 66 min 119 min 14 min 108 min 141 min respectively overall median aggregate acquisition time 31 25 36 min preimplementation period 18 15 22 min postimplementation period difference 13 min 42 median acquisition time reduced 4 min 25 br 140 min 44 br+ 14 min 38 ms 11 min 52 mml 16 min 35 eplconclusion implementation fast brain mri sequences significantly reduced acquisition times commonly performed outpatient brain mri protocolspmid34635436 doi101016 jacra202107011,0.0
parkinsonism motor neuron disorders lessons western pacific als#x2f pdc j neurol sci 2021 oct 2120021 doi 101016 jjns2021120021 online ahead printabstractrecognized worldwide unusual overlap syndrome parkinsonism motor neuron disease without dementia best exemplified former highincidence clusters amyotrophic lateral sclerosis parkinsonismdementia complex als pdc guam usa kii peninsula honshu island japan papua indonesia western side new guinea western pacific als pdc disappearing neurodegenerative disorder multiple sometime overlapping phenotypes als atypical parkinsonism dementia appear constitute single disease environmental origin particular exposure genotoxins neurotoxins seed cycad plants cycas spp formerly used traditional source food guam medicine guam kiijapan papuaindonesia seed compounds include principal cycad toxin cycasin active metabolite methylazoxymethanol mam nonprotein amino acid nmethylaminolalanine lbmaa reproduces components als pdc neuropathology individually administered laboratory species single doses perinatally mam lbmaa repeatedly prolonged periods young adult animals lbmaa human exposure mam potent dnaalkylating mutagen also potential relevance high incidence diverse mutations found among guamanians without als pdc sum seven decades intensive study als pdc revealed field laboratory approaches leading discovery disease etiology now applied sporadic neurodegenerative disorders als beyond western pacific region article part special issue parkinsonism across spectrum movement disorders beyond edited joseph jankovic daniel d truong matteo bolognapmid34635325 doi101016 jjns2021120021,0.0
sporadic facial angiofibroma sporadic angiomyolipoma mimicking tuberous sclerosis complex j med genet 2021 oct 11jmedgenet2021108160 doi 101136 jmedgenet2021108160 online ahead printabstracttuberous sclerosis complex tsc genetic syndrome due mutations either tsc1 tsc2 leading development hamartomatous tumours multiple body sites including facial skin facial angiofibroma faf brain cortical tubers kidney angiomyolipoma aml report describe individual minimal tsc clinical features mutation identified nmi prior genetic testing clinical laboratory massively parallel sequencing mps analysis multiple samples different body sites tumours including blood saliva normal skin aml faf revealed extraordinary situation faf aml completely independent inactivating biallelic variants tsc2 present matched samples suggests two different lesions aml faf due underlying germline mosaic mutation rather likely sporadic events case demonstrates relevance thorough clinical examination highcoverage mps multiple tumours matched normal tissues appropriate genetic counselling individuals marginal tsc features possible tsc1 tsc2 mosaicismpmid34635572 doi101136 jmedgenet2021108160,0.0
realworld application autologous hematopoietic stem cell transplantation 507 patients multiple sclerosis j neurol 2021 oct 11 doi 101007 s00415021108202 online ahead printabstractobjective investigate results realworld application nonmyeloablative autologous hsct multiple sclerosis ms methods july 2003 october 2019 single center northwestern university 414 patients relapsing remitting ms rrms 93 patients newly diagnosed secondary progressive ms spms underwent nonmyeloablative hsctresults one treatmentrelated death 019 due hospitalacquired legionella pneumonia one patient developed neutropenic bacteremia klebsiella pneumonia without sepsis overall 5year survival 988 post hsct secondary autoimmune diseases 2nd ads idiopathic thrombocytopenia itp hypo hyperthyroidism itp highest alemtuzumab 14 0 28 nonalemtuzumab regimens hsct 16 patients developed hypothyroidism 35 15 developed hyperthyroidism graves disease 33 relapse free survival rfs 5 years rrms spms 801 981 respectively progression free survival pfs 4 years rrms spms 95 versus 66 respectively patients rrms edss significantly improved p 00001 followup prehsct mean 387 251 250 241 233 219 1 2 3 4 5 years respectively spms edss improved significantly 1 year thereafter spms mean baseline edss 509 changed posthsct 485 p 004 488 p 02 492 p 27 472 p 007 42 p 021 1 2 3 4 5 years respectivelyconclusion patients rrms autologous nonmyeloablative hsct effective onetime therapy hsct appears less benefit newly diagnosed spmspmid34633525 doi101007 s00415021108202,1.0
cortical plasticity causes useless hand syndrome multiple sclerosis neurophysiological study rare case somatosens mot res 2021 oct 1113 doi 101080 0899022020211986384 online ahead printabstractbackground useless hand syndrome uhs rare clinical manifestation upper cervical cord lesion commonly associated multiple sclerosis ms pathophysiological mechanism underlying uhs remains unclearcase report 25yearold woman described numbness left upper extremity cervical magnetic resonance imaging revealed posterior upper cervical cord lesion cortical lesion explain clinical findings measured 1 shortlatency afferent inhibition sai obtaining motor evoked potentials indicator sensorimotor integration 2 somatosensorial temporal discrimination threshold stdt display central somatosensory pathway function right cerebral hemisphere found excessive increase stdt inhibition sai paradigmconclusions findings indicate impairment sensorimotor integration central processing sensory stimuli cause useless hand syndromepmid34632929 doi101080 0899022020211986384,0.0
early unrestricted access highefficacy diseasemodifying therapies consensus optimize benefits people living multiple sclerosis j neurol 2021 oct 9 doi 101007 s00415021108368 online ahead printabstractearly intervention highefficacy diseasemodifying therapy dmt may best strategy delay irreversible neurological damage progression multiple sclerosis ms european healthcare systems however patient access dmts ms often restricted later stages disease due restrictions reimbursement despite broader regulatory labels although every patient treated dmts initial stages disease early unrestricted access dmts positive benefitrisk profile reasonable value proposition will provide freedom choice appropriate treatment based shared decision expert physicians patients will optimize outcomes facilitate efficient resource allocation sustainability healthcare systems societypmid34626224 doi101007 s00415021108368,0.0
blocking kallikrein 6 promotes developmental myelination glia 2021 oct 9 doi 101002 glia24100 online ahead printabstractkallikrein related peptidase 6 klk6 secreted serine protease highly expressed oligodendrocytes implicated demyelinating conditions gain insights significance klk6 oligodendrocyte biology investigated impact global klk6 gene knockout cns developmental myelination using spinal cord male female mice model results demonstrate constitutive loss klk6 expression accelerates oligodendrocyte differentiation developmentally including increases expression myelin proteins mbp plp cnpase number cc1+ mature oligodendrocytes myelin thickness end first postnatal week coordinate elevations promyelinating signaling pathways erk akt expression fatty acid 2hydroxylase myelin regulatory transcription factor also observed spinal cord 7d klk6 knockouts lc ms ms quantification spinal cord lipids showed sphingosine sphingomyelins elevated klk6 knockouts peak myelination oligodendrocyte progenitor cells opcs derived klk6 knockouts wild type opcstreated klk6 inhibitor dfkz251 also showed increased mbp plp moreover inhibition klk6 opc cultures enhanced brain derived neurotrophic factordriven differentiation altogether findings suggest oligodendrocytederived klk6 may operate autocrine paracrine rheostat brake promyelinating signaling serving regulate myelin homeostasis developmentally adult findings document first time inhibition klk6 globally specifically oligodendrocyte progenitors strategy increase early stages oligodendrocyte differentiation myelin production cnspmid34626143 doi101002 glia24100,1.0
readmission cardiac noncardiac causes among adults epilepsy multiple sclerosis nationwide analysis epilepsy behav 2021 oct 5 124108338 doi 101016 jyebeh2021108338 online ahead printabstractpurpose aim study determine proportions 30day cardiac readmissions adults epilepsy compared multiple sclerosis ms neither condition predictors causes readmissions also examinedmethods used 2014 nationwide readmissions database icd9cm codes identify people epilepsy ms without epilepsy ms multinomial logistic regressions fitted 1 examine association 30day readmissions epilepsy ms neither 2 describe causes predictors 30day readmission cardiac readmissions epilepsyresults 6 870 508 adults admitted 2014 202 938 298 epilepsy 29 556 045 ms proportion 30day readmission epilepsy ms respectively 1 due cardiac causes 017 vs 013 2 due causes 1389 vs 1061 odds 30day cardiac readmission epilepsy ms lower compared without either condition 064 95 ci 057073 p 00001 060 95 ci 043084 p 0003 among epilepsy increasing age 103 95 ci 102104 p 00001 charlson comorbidity index 1 179 95 ci 124260 p 0002 associated higher odds 30day cardiac readmission higher proportion epilepsy readmitted within 30days due cardiac causes died hospital 1009 compared ms reportable due cell frequency 10 without epilepsy ms 561 conclusion admitted hospital living epilepsy higher proportion cardiac readmissions death hospital compared living ms determinants likely multifactorial findings important need explored identify strategies prevent readmissions due cause treatments reduce mortalitypmid34624805 doi101016 jyebeh2021108338,0.0
impact smoking cessation multiple sclerosis disease progression brain 2021 oct 8awab385 doi 101093 brain awab385 online ahead printabstractthe negative impact smoking ms well established however much less evidence whether smoking cessation beneficial progression ms adults ms registered united kingdom ms register 20112020 formed retrospective prospective cohort study primary outcomes changes 3 patient reported outcomes pros normalised ms physical impact scale msis29phys normalised ms walking scale msws12 hospital anxiety depression scale hadsanxiety hadsdepression time event outcomes clinically significant increases pros 7983 participants included 4130 517 ever smoked 1315 165 current smokers 2815 4130 682 former smokers pros current smokers time completing first questionnaire higher pro scores indicating higher disability compared never smoked 10 points difference msis29phys msws12 1518 point hadsanxiety hadsdepression improvement pro scores increasing time since quitting former smokers 923 participants formed prospective parallel group demonstrated msis29phy 503 371 634 msws12 528 362 694 hadsdepression 071 047 096 worsened period 4 years whereas hadsanxiety remained stable smoking status significant year 4 current smokers higher msis29phys hadsanxiety scores 305 022 588 114 052 176 former smokers lower msis29 score 291 503 079 4642 participants comprised time event analysis still smoking associated shorter time worsening event pros msis29phys n 4436 p 00013 msws12 n 3902 p 00061 hadsanxiety n 4511 p 00017 hadsdepression n 4511 p 00001 worsening motor disability msis29phys msws12 independent baseline hadsanxiety hadsdepression scores statistically significant difference rate worsening never former smokers smokers quit slowing rate motor disability deterioration matches rate motor decline never smoked suggests smoking cessation beneficial people mspmid34623418 doi101093 brain awab385,0.0
flair2 postprocessing improving ms lesion detection standard ms imaging protocols j neurol 2021 oct 8 doi 101007 s0041502110833x online ahead printabstractbackground technical improvements magnetic resonance imaging mri acquisition higher field strength optimized sequences lead better multiple sclerosis ms lesion detection characterization multiplication 3dflair 3dt2 sequences flair2 results isovoxel images increased contrasttonoise ratio increased whitegraymatter contrast improved ms lesion visualization without increasing mri acquisition time current study aims assess potential 3dflair2 detecting cortical leucocortical lc juxtacortical jc white matter wm lesionsobjective compare lesion detection 3dflair2 stateoftheart 3dt2flair 3dt2weighted imagesmethods retrospectively analyzed mri scans thirteen ms patients showing previously noted high cortical lesion load scans acquired using 3 t mri scanner wm jc lc lesions manually labeled manually counted randomization 3dt2 3dflair 3dflair2 scans using itksnap toolresults lc lesion visibility significantly improved 3dflair2 comparison 3dflair 4 vs 1 p 0018 3dt2 4 vs 1 p 0007 comparing lc lesion detection 3dflair2 vs 3dflair 3dflair2 detected average 32 cortical lesions 95 ci 91 28 comparing 3dt2 3dflair2 detected average 37 lc lesions 95 ci 33107 conclusions 3dflair2 easily applicable timesparing mr postprocessing method improve cortical lesion detection larger sampled studies warranted validate sensitivity specificity 3dflair2pmid34623512 doi101007 s0041502110833x,0.0
caregivers#39 use personal social resourcefulness differences care recipient condition west j nurs res 2021 oct 81939459211050951 doi 101177 01939459211050951 online ahead printabstractalthough family caregivers use personal social resourcefulness skills best health outcomes unknown whether tendency toward personal social resourcefulness varies care recipients condition crosssectional study existing data 234 caregivers persons various conditions examined five item pairs resourcefulness scale responses capturing personal social resourcefulness relation anxiety anger sadness indecision financial distress caregivers categorized recipients condition amyotrophic lateral sclerosis cancer dementia mental illness parkinsons disease stroke traumatic brain injury multiple conditions findings showed across groups caregivers used personal social resourcefulness angry sad indecisive personal resourcefulness anxious managing money caregivers persons cancer traumatic brain injury stroke mental illness differed findings provide basis future clinical trials across diverse caregiver groupspmid34622720 doi101177 01939459211050951,0.0
effects cognition dmts multiple sclerosis moving beyond prevention inflammatory activity j neurol 2021 oct 7 doi 101007 s0041502110832y online ahead printabstractin review critically summarize recent findings derived randomized controlled trials rcts observational studies metaanalyses published last 3 years included effects dmts cognitive performances among outcomespmid34618224 doi101007 s0041502110832y,0.0
mdivi1 modulates macrophage#x2f microglial polarization mice eae via inhibition tlr2#x2f 4gsk3nfb inflammatory signaling axis mol neurobiol 2021 oct 7 doi 101007 s12035021025521 online ahead printabstractmacrophage microglial modulation plays critical role pathogenesis multiple sclerosis ms inflammatory disorder central nervous system dynaminrelated protein 1 cytoplasmic molecule regulates mitochondrial fission proven mitochondrial fission inhibitor 1 mdivi1 small molecule inhibitor drp1 can relieve experimental autoimmune encephalomyelitis eae preclinical animal model ms whether macrophages microglia involved pathological process mdivi1treated eae remains determined studied antiinflammatory effect mdivi1 mice oligodendrocyte glycoprotein peptide3555 mog3555 induced eae found drp1 phosphorylation serine 616 macrophages microglia decreased mdivi1 treatment accompanied decreased antigen presentation capacity macrophages microglia eae mouse spinal cord mdivi1 treatment caused macrophage microglia produce low levels proinflammatory molecules cd16 32 inos tnf high levels antiinflammatory molecules cd206 il10 arginase1 suggesting mdivi1 promoted macrophage microglia shift inflammatory m1 phenotype antiinflammatory m2 phenotype moreover mdivi1 able downregulate expression trl2 trl4 gsk3 phosphorylated nfbp65 prevent nfbmediated il1 il6 production conclusion results indicate mdivi1 significantly alleviates inflammation mice eae promoting m2 polarization inhibiting tlr2 4 gsk3mediated nfb activationpmid34618332 doi101007 s12035021025521,0.0
clinical laboratory features children tremor singlecenter experience acta neurol belg 2021 oct 7 doi 101007 s13760021018040 online ahead printabstractaim tremor involuntary rhythmic oscillatory movement body parts around central point plane arises contraction antagonist muscles evaluation pediatric patients tremor can challenging due limited populationbased studies children aim study evaluate demographic clinical laboratory features childhood tremor retrospectivelymaterials methods patients age 18 years presenting tremor n 111 pediatric neurology unit kecioren research training hospital january 2014 december 2019 included study patients neuromuscular disease vertebral pathology incomplete data hospital records included also benign tremor causes jitteriness shuddering attack etc seen neonatal infancy period excluded study number patients insufficient demographic data type duration tremor accompanying symptoms chronic diseases medications family history physical neurological examination laboratory findings neuroimaging findings retrospectively analyzed recordedresults total 111 children 59 girls 52 boys included study female male ratio 11 mean age tremor onset age admission hospital 132 28 years range 417 years 148 20 years range 617 years respectively common type tremor essential tremor 622 followed enhanced physiologic 189 none patients acute metabolic disorder diagnostic tests revealed etiology 12 patients vitamin b12 deficiency 11 patients multiple sclerosis one patient druginduced taskspecific tremors determined 4 patients determined patients positive family history tremor appeared noticed younger ageconclusions cases tremor can diagnosed accurately detailed medical history physical neurological examination essential tremor common type tremor children laboratory tests imaging methods limited additional yield elucidating etiology early recognition tremor related signs symptoms childhood important detection treatment possible underlying causepmid34618342 doi101007 s13760021018040,0.0
utility paramagnetic rim lesions 15t susceptibility phase imaging diagnosis pediatric multiple sclerosis pediatr radiol 2021 oct 6 doi 101007 s00247021051884 online ahead printabstractbackground studies suggested paramagnetic rim lesions 7tesla t 3t susceptibilitybased brain mri specific features multiple sclerosis ms lesions adultsobjective aim study investigate whether presence paramagnetic rim lesions 15t phase images can help discriminate pediatric patients ms demyelinating diseasesmaterials methods retrospective study reviewed brain mris performed 15t scanners included susceptibilityweighted imaging swi sequences phase images children younger 18 years diagnosed ms acquired demyelinating syndromes case five white matter lesions selected using t2 fluidattenuated inversion recovery images paramagnetic rim evaluation swi two researchers performed independent assessments presence paramagnetic rim lesions discrepancies settled consensus input senior neuroradiologistresults included 13 children diagnosed ms 16 children diagnosed nonms demyelinating diseases analyzed total 132 focal white matter lesions seventyone percent lesions ms group paramagnetic rims none lesions nonms group rims one children ms least one lesion paramagnetic rim presence one lesion paramagnetic rim 15t phasecontrast images resulted 70 sensitivity 100 specificity msconclusion paramagnetic rim lesions detected 15t phasecontrast mr images can help discriminate ms acquired demyelinating syndromes pediatric populationpmid34611736 doi101007 s00247021051884,1.0
trend analysis neurological disorders major causes death disability according human development 19902019 environ sci pollut res int 2021 oct 5 doi 101007 s11356021166045 online ahead printabstractthis study aims assess trends incidence rate neurological disorders developed developing countries worldwide 19902019 agestandardized incidence rate per 100000 persons neurological disorders primary outcome extracted global burden disease database 189 countries territories 1990 2019 using human development index hdi countries classified developed hdi 07 developing hdi 07 groups longitudinal analysis performed using latent growth model lgm assess change incidence rate neurological disorders time groups developed countries increasing rate related depressive disorders rising rate 4015 100000 every five years p 0001 alzheimers dementia parkinson multiple sclerosis next rank increasing rates 877 124 02 respectively p 0001 time significant decreasing trend determined related conducting disorder attentiondeficit hyperactivity meningitis anxiety eating disorders rates 1392 496 27 16 144 respectively p 005 developing countries meningitis conduct disorder attentiondeficit hyperactivity stroke autism spectrum showed significant decreasing trend time rates 1545 584 256 186 107 respectively p 005 headache disorder increasing rate 795 following depressive rate 3532 substance use rate 1499 anxiety rate 718 eating rate 34 disorders also alzheimers dementia bipolar disorder schizophrenia parkinsons brain central nervous system cancer multiple sclerosis next rank significant increasing trends p 005 given high economic social burden neurological disorders rate diseases countries seem dropped remarkably heterogeneous incidence rate world countries seems due underestimating gaps epidemiological information necessary provide exact registry systems health policies especially developing countriespmid34609680 doi101007 s11356021166045,0.0
illness representations psychological outcomes chronic lymphocytic leukaemia br j health psychol 2021 oct 4 doi 101111 bjhp12562 online ahead printabstractobjectives chronic lymphocytic leukaemia cll lifelong cancer subtle symptoms treatment curative often involves repeated relapses retreatments illness perceptions cognitive emotional representations illness stimuli studied cll patients 1 identify illness perception profiles prior treatment 2 test whether profile membership predicts psychological responses 12 months later treatment continueddesign cll patients n 259 randomized one four cancer treatment trials testing targeted therapy assessed starting treatment 12 monthsmethods brief illness perception questionnaire bipq assessed perceived consequences timeline personal treatment control identity comprehension concern emotions toward cll psychological outcomes depressive symptoms phq9 bdiii negative mood poms cancer stress iesr latent profile analysis lpa determined number profiles differential bipq items profile multilevel models tested profiles predictors 12month psychological outcomesresults lpa selected threeprofile model profiles revealing low n 150 579 moderate n 21 81 highimpact n 88 340 illness representations profiles defined differences consequences identity concern emotions profile membership predicted psychological outcomes ps038 lowimpact profile patients endorsed minimal psychological symptoms highimpact profile patients reported substantial symptomsconclusions results first cll illness representation study provide directions future clinical efforts identifying differences among patients perceptions cll consequences symptom burden concerns emotional responses atrisk patient group might receive tailored psychological treatment treatments may address negative perceptions reduce psychological risk associated chronic cancerpmid34608724 doi101111 bjhp12562,0.0
selfreported work productivity people multiple sclerosis association mental physical health disabil rehabil 2021 oct 5110 doi 101080 0963828820211981468 online ahead printabstractpurpose study aimed identify mental health physical health demographic disease characteristics relating work productivity people multiple sclerosis ms methods crosssectional study 236 employed people ms median age 42 years 788 female underwent neurological neuropsychological assessments additionally completed questionnaires inquiring work productivity presenteeism reduced productivity working absenteeism loss productivity due absence work mental physical health demographic disease characteristics multiple linear logistic regression analyses performed presenteeism absenteeism dependent variables respectivelyresults model mental physical health factors significantly predicted presenteeism f 11 202 1133 p 0001 r2 038 higher cognitive p 0001 physical impact p 0042 fatigue associated presenteeism model mental health factors significantly predicted absenteeism 2 11 3772 p 0001 r2 027 nagelkerke r2 016 cox snell specifically observed symptoms depression p 0041 higher cognitive impact fatigue p 0011 significantly associated absenteeismconclusions people ms cognitive physical impact fatigue positively related presenteeism symptoms depression cognitive impact fatigue positively related absenteeismimplications rehabilitationmultiple sclerosis ms affects people working age significantly interfering work productivityhigher cognitive physical impact fatigue associated presenteeism workers msa higher cognitive impact fatigue depressive symptoms associated absenteeism workers msoccupational healthcare professionals aware impact physical mental health work productivity workers mspmid34607481 doi101080 0963828820211981468,0.0
cd4+ tcell dna methylation changes pregnancy significantly correlate diseaseassociated methylation changes autoimmune diseases epigenetics 2021 oct 4116 doi 101080 1559229420211982510 online ahead printabstractepigenetics may play central yet unexplored role profound changes maternal immune system undergoes pregnancy involved pregnancyinduced modulation several autoimmune diseases investigated changes methylome isolated circulating cd4+ tcells nonpregnant pregnant women 1st 2nd trimester using illumina infinium human methylation 450k array explored changes related autoimmune diseases known affected pregnancy pregnancy associated several hundreds methylation differences particularly 2nd trimester networkbased modular approach identified several genes eg cd28 fyn vav1 pathways related tcell signalling activation highlighting tcell regulation central component observed methylation alterations identified pregnancy module significantly enriched diseaseassociated methylation changes related multiple sclerosis rheumatoid arthritis systemic lupus erythematosus negative correlation pregnancyassociated methylation changes diseaseassociated changes found multiple sclerosis rheumatoid arthritis diseases known improve pregnancy whereas positive correlation found systemic lupus erythematosus disease instead worsens pregnancy thus directionality observed changes line previously observed effect pregnancy disease activity systems medicine approach supports importance methylome immune regulation tcells pregnancy findings highlight relevance using pregnancy model understanding identifying diseaserelated mechanisms involved modulation autoimmune diseasesabbreviations bmiq betamixture quantile dilation dmgs differentially methylated genes dmps differentially methylated probes fe fold enrichment fdr false discovery rate go gene ontology gwas genomewide association studies mds multidimensional scaling ms multiple sclerosis pbmc peripheral blood mononuclear cells pbs phosphate buffered saline ppi proteinprotein interaction ra rheumatoid arthritis sd standard deviation sle systemic lupus erythematosus snp single nucleotide polymorphism th cd4+ t helper cell vista divisive shuffling approachpmid34605719 doi101080 1559229420211982510,0.0
immune response multiple sclerosis annu rev pathol 2021 oct 4 doi 101146 annurevpathol052920040318 online ahead printabstractmultiple sclerosis ms chronic autoimmune inflammatory neurodegenerative disease affects central nervous system cns ms characterized immune dysregulation results infiltration cns immune cells triggering demyelination axonal damage neurodegeneration although exact causes ms fully understood genetic environmental factors thought control ms onset progression article review main immunological mechanisms involved ms pathogenesis expected final online publication date annual review pathology mechanisms disease volume 17 january 2022 please see http wwwannualreviewsorg page journal pubdates revised estimatespmid34606377 doi101146 annurevpathol052920040318,1.0
systemic sclerosis tapse#x2f spap ratio can used addition detect algorithm pulmonary arterial hypertension diagnosis rheumatology oxford 2021 oct 4keab748 doi 101093 rheumatology keab748 online ahead printabstractobjective early detection pulmonary arterial hypertension pah crucial improve patient outcomes aim study compare positive predictive value ppv echocardiographyderived tricuspid annular plane systolic excursion systolic pulmonary artery pressure tapse spap ratio detect algorithm pah screening cohort systemic sclerosis ssc patientsmethods 51 ssc patients screened pah using detect algorithm echocardiographyresults echocardiography recommended detect algorithm step 1 34 patients 667 right heart catheterization rhc recommended detect algorithm step 2 16 patients 314 pah confirmed rhc 5 patients detect algorithm positive predictive value ppv 313tapse spap ratio higher ssc patients referred rhc ssc patients referred rhc according detect algorithm step 2 083 035140 mm mmhg vs 074 012109 mm mmhg p 005 using cutoff 060 mm mmhg 8 157 ssc patients tapse spap ratio 060 mm mmhg pah confirmed rhc 5 patients ppv tapse spap 625in multiple regression analysis tapse spap associated age coefficient 0348 95 ci 0011 0003 p 001 detect algorithm step 1 coefficient 1023 95 ci 00060024 p 001 detect algorithm step 2 coefficient 1758 95 ci 0059 0021 p 00001 conclusion ssc patients detect algorithm step 2 total score 35 tapse spap ratio can used select patients requiring rhc confirm pah diagnosispmid34605890 doi101093 rheumatology keab748,0.0
decreased astrocytic ccl2 accounts baf312 effect pbmcs transendothelial migration blood brain barrier vitro model j neuroimmune pharmacol 2021 oct 2 doi 101007 s11481021100165 online ahead printabstractdisruption blood brain barrier bbb common event several neurological diseases particular multiple sclerosis ms contributes infiltration central nervous system peripheral inflammatory cells sphingosine1phosphate s1p bioactive molecule pleiotropic effects agonists s1p receptors fingolimod siponimod baf312 clinical practice ms shown preserve bbb function inflammatory conditions using vitro bbb model endothelialastrocytes coculture exposed inflammatory insult tumor necrosis factor interferon ti show baf312 reduced migration peripheral blood mononuclear cells pbmcs endothelial layer presence astrocytes effect accompanied decreased expression adhesion molecule icam1 baf312 also reduced activation astrocytes controlling nfkb nlrp3 induction preventing increase proinflammatory cytokine chemokines reduction ccl2 baf312 may responsible observed effects accordingly addition exogenous ccl2 able counteract baf312 effects rescued ti responses pbmc migration icam1 expression astrocyte activation present results point baf312 effects bbb properties suggesting also key role astrocytes mediating drug effects endothelial functionpmid34599741 doi101007 s11481021100165,0.0
experiences attitudes lifestyle modification management multiple sclerosis qualitative analysis freetext survey data health expect 2021 oct 2 doi 101111 hex13364 online ahead printabstractbackground growing evidence suggests role lifestyle modification improved health outcomes people multiple sclerosis pwms however perspectives pwms engage lifestyle modification lackingobjective explored perspectives pwms regarding modification lifestylerelated risk factors multiple sclerosis ms disease management understand attitudes experiences lifestyle modification part selfmanagement patient perspectivedesign participants 18 years english speaking responded freetext openended question health outcomes lifestyle sample pwms holism international online survey responses analysed utilizing inductive thematic analysisresults exploration lifestyle modification themes describing experiences attitudes participants included practical challenges physical psychological barriers enablers change experienced outcomes although participants reported practical psychological challenges adoption maintenance lifestyle behaviours many expressed ability gain control ms engagement lifestyle behaviours development hope optimism accompanied sense control times leading sense personal transformationconclusion findings highlight challenges experienced pwms adopting lifestyle modifications disease management well positive benefits following healthy lifestyle behaviours findings may form basis focussed qualitative explorations experiences outcomes lifestyle modification ms futurepatient contribution consenting pwms completed survey capturing data demographics clinical course lifestyle behaviours health outcomespmid34599857 doi101111 hex13364,0.0
conjunctival impression cytology tear film parameters patients multiple sclerosis int ophthalmol 2021 oct 1 doi 101007 s10792021020315 online ahead printabstractpurpose evaluate conjunctival impression cytology cic findings tear film parameters patients multiple sclerosis ms compared controlsmethods thirtythree patients ms ms group 33 age sexmatched healthy subjects control group included crosssectional comparative study cic grades tear breakup time tbut schirmer 1 test results ocular surface disease index osdi scores compared two groups correlations cic grade tbut schirmer 1 test result osdi score expanded disability status scale score disease duration analyzedresults mean cic grade higher ms group control group 148 071 039 056 respectively p 0001 ms group cic 14 participants 424 grade 23 control group cic one participant 33 grade 2 none grade 3 tbut 812 316 1306 423 s ms control groups respectively p 0001 schirmer 1 test results 845 575 1736 1089 mm ms control groups respectively p 0001 lower osdi score 3636 1919 1370 1536 ms control groups respectively p 0001 higher ms group compared control groupconclusion patients ms objective findings dry eye subjective symptoms related dry eye cic abnormalities including high grades conjunctival squamous metaplasia goblet cell loss common patients ms monitored ocular surface alterations dry eye diseasepmid34599424 doi101007 s10792021020315,0.0
role plasma exchange treatment refractory autoimmune neurological diseases narrative review j neuroimmune pharmacol 2021 oct 2 doi 101007 s11481021100049 online ahead printabstractautoimmune neurological disorders commonly treated immunosuppressive therapy patients refractory conditions standard immunosuppression often insufficient complete recovery prevent relapses patients rely treatments manage disease treatment refractory cases differs diseases intravenous immunoglobulin plasma exchange plex immunemodulating treatments commonly used review focus five autoimmune neurological disorders themes 2018 midlands neurological society meeting plex refractory neurology autoimmune encephalitis ae multiple sclerosis ms neuromyelitis optica spectrum disorders nmosd chronic inflammatory demyelinating polyradiculoneuropathy cidp myasthenia gravis mg diagnosis inflammatory neuropathies often challenging plex can effective refractory autoimmune diseases ineffectiveness can confounded misdiagnosis one example poems syndrome characterized polyneuropathy organomegaly endocrinopathy myeloma protein skin changes often wrongly diagnosed cidp cidp responds well plex poems accurate diagnosis therefore essential success rates can also differ within one disease eg response rates plex considerably higher refractory relapsing remitting ms compared primary secondary progressive ms sufficient efforts made correctly pinpoint diagnosis along type subtype refractory autoimmune disease plex immunotherapies can play valuable role patient managementpmid34599742 doi101007 s11481021100049,1.0
deep learning algorithm white matter hyperintensity lesion detection segmentation neuroradiology 2021 oct 2 doi 101007 s0023402102820w online ahead printabstractpurpose white matter hyperintensity wmhi lesions mr images important indication various types brain diseases involve inflammation blood vessel abnormalities automated quantification wmhi can valuable clinical management patients existing automated software often developed single type disease may applicable clinical scans thick slices different scanning protocols purpose study develop validate algorithm automatic quantification white matter hyperintensity suitable heterogeneous mri data different disease typesmethods developed evaluated deepwml deep learning method fully automated white matter lesion wml segmentation multicentre flair images used mri 507 patients including three distinct white matter diseases obtained 9 centres wide range scanners acquisition protocols automated delineation tool evaluated quantitative parameters dice similarity sensitivity precision compared manual delineation gold standard results overall median dice similarity coefficient 078 range 064 086 across three disease types multiple centres median sensitivity precision 084 range 067 094 081 range 064 092 respectively tools performance increased larger lesion volumesconclusion deepwml successfully applied wide spectrum mri data three white matter disease types potential improve practical workflow white matter lesion delineationpmid34599377 doi101007 s0023402102820w,0.0
costutility oral methylprednisolone treatment multiple sclerosis relapses results copousep trial rev neurol paris 2021 sep 28s00353787 21 006640 doi 101016 jneurol202106009 online ahead printabstractbackground studies shown oral highdose methylprednisolone mp noninferior intravenous mp treating multiple sclerosis relapses terms effectiveness tolerance order assist resource allocation decisionmaking costeffectiveness must also assessed objective evaluate costutility per os highdose mp well costsavings associated implementing strategymethods costutility analysis 28 days carried using data french copousep multicenter doubleblind randomized controlled noninferiority trial statutory health insurance reimbursement database costs calculated using societal perspective including direct indirect costs incremental costeffectiveness ratio calculated bootstrapping methods assessed uncertainty surrounding results alternative scenario analysis mp administered home also carried budgetary impact analysis carried five yearsresults conditions trial hospitalized patients significant difference utilities costs 28 days incremental costeffectiveness ratio 15 360 per qualityadjusted lifeyear gained multiple sclerosis relapses treated home oral mp effective less costly associated annual savings 25 million euros french healthcare systemconclusions oral mp costeffective treatment multiple sclerosis relapses associated major savingspmid34598781 doi101016 jneurol202106009,0.0
assessing preanalytical variability plasma cerebrospinal fluid processing effects inflammationrelated protein biomarkers mol cell proteomics 2021 sep 28100157 doi 101016 jmcpro2021100157 online ahead printabstractproteomics studies important discovery new biomarkers clinical tools diagnosis disease monitoring however preanalytical variations caused differences sample handling protocol pose challenges assessing biomarker reliability comparability studies purpose study examine effects delayed centrifuging measured protein levels plasma csf blood healthy individuals patients multiple sclerosis along csf patients suspected neurological disorders left room temperature different time periods blood 1 24 48 72 hours csf 1 6 hours prior centrifuging ninetyone inflammationrelated proteins analyzed using proximity extension assay high sensitivity multiplex immunoassay additional metabolic neurology related markers also investigated csf summary many proteins particularly plasma increased levels longer delays processing likely due part intracellular leakage levels casp8 il8 il18 sirt2 st1a1 increased 210 fold plasma 24 hours room temperature similarly levels ctsh entpd5 wwp2 differentiated csf 6 hour delay processing however rate change many proteins relatively consistent therefore able characterize biomarkers detecting sample handling variability findings highlight importance timely consistent sample collection need increased awareness protein susceptibility sample handling bias addition suggested biomarkers may used certain situations detect correct preanalytical variation future studiespmid34597789 doi101016 jmcpro2021100157,0.0
fingolimod first secondline treatment miniseries young hellenic patients adolescentonset multiple sclerosis focus immunological data neurol sci 2021 oct 1 doi 101007 s10072021056232 online ahead printabstractbackground pediatric onset multiple sclerosis poms characterized highly active profile often warranting treatment high efficacy diseasemodulating therapies dmts fingolimod oral sphingosine1phosphate receptor modulator first food drug administration fda european medicines agency ema approved dmt treatment pomsobject aim present realworld data seven fingolimodtreated pomspatients recruited single ms center greecemethods clinical imaging laboratory data 7 hellenic patients fulfilling international pediatric multiple sclerosis study group ipmssg criteria poms diagnosis received fingolimod treatment selected human leukocyte antigen hla genotyping performed standard lowresolution sequencespecific oligonucleotide techniquesresults three patients treatmentnave adolescents received fingolimod firstline treatment two experienced ongoing clinical radiological disease activity switched natalizumab remaining cases postadolescent adults poms vast majority experienced total neartotal disease remission fingolimod generally welltolerated two patients high disease activity carried hladrb103 allele five patients carriers least one hladrb104 hladrb113 hladrb114 alleles combined hladrb103 showed trend towards favorable clinical course fingolimod responders showed trend towards increased cd 1656 +nk cell counts immunophenotyping assaysconclusions preliminary results support response poms patients fingolimod may partially dependent age previous dmt younger treatmentnave patients presenting worse outcomes role immunogenetics immunophenotyping personalized treatment warrants investigation larger diverse populationspmid34596776 doi101007 s10072021056232,0.0
treatment response scoring systems assess longterm prognosis selfinjectable dmts relapsingremitting multiple sclerosis patients j neurol 2021 oct 1 doi 101007 s0041502110823z online ahead printabstractbackground objectives different treatment response scoring systems treated ms patients exist objective assess longterm predictive value systems rrms patients treated selfinjectable dmtsmethods rrmstreated patients underwent brain mri onset therapy 12 months thereafter neurological assessments every 6 months clinical demographic characteristics collected baseline first year treatment several scoring systems rio score rs modified rio score mrs magnims score ms road score ros calculated coxregression survival analyses performed identify scores predicting longterm disabilityresults included 319 rrms patients survival analyses showed patients rs 1 ros 3 significant risk reaching edss 40 60 score best sensitivity 61 ros mrs showed best specificity 88 rs showed best positive predictive value 42 best accuracy 81 conclusions combined measures integrated different scores acceptable prognostic value identifying patients longterm disability thus data reinforce concept early treatment optimization minimize risk longterm disabilitypmid34596743 doi101007 s0041502110823z,0.0
immunosuppression multiple sclerosis neurologic disorders handb exp pharmacol 2021 oct 1 doi 101007 164_2021_545 online ahead printabstractmultiple sclerosis ms autoimmune disease central nervous system cns characterized peripheral immune cell infiltration brain spinal cord demyelination glial cell activation neuronal damage currently cure ms however available diseasemodifying agents minimize inflammation cns various mechanisms approved drugs lessen severity disease delay disease progression however still suboptimal patients experience adverse effects varying efficacies additionally one diseasemodifying therapy available debilitating progressive form ms chapter focuses presentlyavailable therapeutics importantly future directions ms therapy based preclinical studies early clinical trials immunosuppression neurological disorders including neuromyelitis optica spectrum disorders myasthenia gravis guillainbarr syndrome also discussedpmid34595582 doi101007 164_2021_545,1.0
uterine pecomatosis tsc1 mutation patient tuberous sclerosis case report literature review int j gynecol pathol 2021 sep 29 doi 101097 pgp0000000000000827 online ahead printabstractuterine pecomatosis rare phenomenon characterized presence multiple perivascular epithelioid cell tumors pecomas microscopic proliferations perivascular epithelioid cells herein report case pecomatosis arising 49yrold woman known history tuberous sclerosis targeted nextgeneration sequencing revealed tsc1 stopgain mutation pq732x tested nodules singlecopy tsc1 loss copyneutral tsc1 loss heterozygosity knowledge second report tsc1 inactivation uterine pecoma first report confirmed tsc1 abnormalities pecomatosispmid34593703 doi101097 pgp0000000000000827,0.0
biochemical markers chronic noninfectious disease human tear film clin exp optom 2021 sep 30111 doi 101080 0816462220211974282 online ahead printabstractthe tear film thin moist layer covering ocular surface laden proteins peptides lipids mucins electrolytes cellular debris function maintain healthy status ocular surface many cases ocular systemic disease integrity layer changed balance constituents disturbed since tears easy quick collect can stored long periods potential valuable source information relevant many disease states purpose review collate information known biomarkers systemic disease identified tears range conditions covered includes diabetes mellitus diabetic retinopathy diabetic peripheral neuropathy multiple sclerosis parkinsons disease alzheimers disease migraine systemic sclerosis cystic fibrosis thyroid disorders cancerpmid34592130 doi101080 0816462220211974282,0.0
autologous atgfree hematopoietic stem cell transplantation refractory autoimmune rheumatic diseases latin american cohort clin rheumatol 2021 sep 29 doi 101007 s10067021059310 online ahead printabstractautologous hematopoietic stem cell transplantation hsct recognized treatment alternative patients severe refractory autoimmune rheumatic diseases ards usually antithymocyte globulin atg containing conditioning regimens employed however atg unavailable developing nations report 15year clinical experience autografting patients ards atgfree conditioning regimen brief assessment patientreported outcomes posthsct patients active disease resistant multiple lines treatment eventfree survival efs assessed using kaplanmeier method eight patients underwent autologous hsct diagnoses included juvenile idiopathic arthritis n 3 systemic lupus erythematosus n 2 systemic sclerosis n 2 rheumatoid arthritis n 1 median time diagnosis hsct 3 years 07519 hematological recovery documented recipients 4 patients 50 completed procedure completely ambulatory setting five 625 patients achieved complete response 3 375 partial response median efs 7 months 95 ci 497902 1year efs rate 219 95 ci 18252576 transplantrelated mortality 0 1 recipient died 8 years posthsct due chronic kidney disease six 75 patients presented steroid dosage reduction posthsct 2 25 perceived improvement functionality despite relapsed hsct viable treatment alternative selected patients severe therapyresistant ards improvement disease management quality life documented need remains elucidate characteristics optimal hsct candidate well adequate conditioning regimen atg available key points despite advances treatment autoimmune rheumatic diseases patients remain refractory context autologous hematopoietic stem cell transplantation hsct rises viable alternative 8 hsct recipients autoimmune rheumatic diseases 5 625 patients achieved complete response 3 375 partial response 1year eventfree survival 219 transplantrelated mortality 0 4 50 patients autografted completely outpatient setting even relapse presented patients reported improvement functionality quality life also better response dmards reduction steroid dependency posthsct documentedpmid34585327 doi101007 s10067021059310,0.0
improved assessment longitudinal spinal cord atrophy multiple sclerosis using registrationbased approach relevance clinical studies j magn reson imaging 2021 sep 28 doi 101002 jmri27937 online ahead printabstractbackground reliable measurements cervical cord atrophy progression may useful monitoring neurodegeneration multiple sclerosis ms purpose compare new registrationbased reg method two existing methods active surface propagation segmentation propseg measure cord atrophy changes time msstudy type retrospectivesubjects cohort eight healthy controls hc 28 ms patients enrolled single institution cohort ii 25 hc 63 ms patients enrolled three european sitesfield strength sequence 3d t1weighted gradient echo sequence acquired 15 t cohort 30 t cohort ii assessment percentage cord area changes pcacs baseline followup cohort 234 years interquartile range 200255 years cohort ii 105 years interquartile range 101118 years evaluated subjects using reg propseg reg included accurate registration baseline followup straightened cord images followed asbased optimized cord segmentation subset studies analyzed twice two observersstatistical tests linear regression models used estimate annualized pcac effect sizes expressed ratio estimated differences hc error term p 005 reproducibility assessed linear mixedeffect models annualized pcacs used sample size calculations significance 005 power 1 080 results annualized pcacs related standard errors ses lower reg methods pcac ms patients 15 t 112 se 022 reg 132 se 030 140 se 033 propseg 30 t pcac 083 se 025 reg 092 se 032 118 se 053 propseg reflected larger effect sizes lower sample sizes intra interobserver agreement range 072091 096 regdata conclusion results support use registration method measure cervical cord atrophy progression future ms clinical studieslevel evidence 3 technical efficacy stage 2pmid34582062 doi101002 jmri27937,0.0
cost illness multiple sclerosis disease characteristics review reviews expert rev pharmacoecon outcomes res 2021 sep 28 doi 101080 1473716720221987218 online ahead printabstractintroduction light increasing number economic burden studies heterogeneity methodology reporting standards need robust evidence synthesis umbrella review levelareas covered carried first review reviews cost illness studies multiple sclerosis focusing disaggregated costs key disease characteristics disability level relapse disease course also characterized underlying methodological evidence base unique individual primary studiesexpert commentary identified 17 reviews encompassing 111 unique primary studies high degree overlap across reviews costs substantial rising disability level relapse episodes disease progression disability key cost driver compared mild disability total costs moderate disability 1423fold higher 1829fold higher severe disability escalating disability share costs outside health system indirect costs informal care increasingly outweighed share direct medical costs 111 primary studies 72 gathered resource use loss data patient selfreport associated costs mostly reported disability level 75 followed relapse 48 disease course 21 conclusion although heterogeneity can make indepth comparisons costs across studies impossible important patterns broadly apparentpmid34582300 doi101080 1473716720221987218,0.0
multiple sclerosis epidemiological trends italy highlight environmental risk factors j neurol 2021 sep 27 doi 101007 s00415021107825 online ahead printabstractitaly definitely highrisk country multiple sclerosis ms last 50 years several epidemiological studies including longitudinal surveys disclosed ms incidence prevalence italy mainland islands sardinia sicily progressively increased picturing semiparabolic curve based comprehensive scrutiny 58 papers conclude latitude risk gradient fit italian map ms genetic heterogeneity italian ethnicities likely forms basis ms predisposition account dramatic increase ms incidence prevalence observed italy last half century rather seems better explained effect environmental factorspmid34580756 doi101007 s00415021107825,0.0
lateonset neutropenia anticd20 therapy multiple sclerosis neuromyelitis optica spectrum disorders mog antibodyassociated disease prospective study rev neurol paris 2021 sep 24s00353787 21 006603 doi 101016 jneurol202106007 online ahead printabstractlateonset neutropenia lon anticd20 therapy poorly described side effect inflammatory disorders cns prospective study patients treated rituximab ocrelizumab ms neuromyelitis optica spectrum disorders mog antibodyassociated disease mogad asked perform complete blood count cbc every two weeks six months aim identifying lon 152 patients two 1 32 absolute neutrophil count 1 000 mm3 one patient mogad agranulocytosis one patient ms grade 3 neutropenia asymptomatic results confirm lon anticd20 therapy inflammatory disorders cns exceptional nevertheless biological complication remains infrequent justify close systematic cbc followuppmid34579948 doi101016 jneurol202106007,0.0
chronic necrotizing aspergillosis new risk teriflunomide multiple sclerosis patients rev neurol paris 2021 sep 24s00353787 21 00669x doi 101016 jneurol202106012 online ahead printno abstractpmid34579947 doi101016 jneurol202106012,0.0
dysregulation iron homeostasis cns role ferroptosis neurodegenerative disorders antioxid redox signal 2021 sep 25 doi 101089 ars20210218 online ahead printabstractsignificance iron accumulation occurs cns variety neurological conditions diverse spinal cord injury stroke multiple sclerosis parkinsons disease others iron redox active metal gives rise damaging free radicals intracellular levels controlled properly sequestered within cells accumulation iron occurs due dysregulation mechanisms control cellular iron homeostasis recent advances molecular mechanisms regulate cellular iron homeostasis revealed much detail past three decades new advances continue made understanding aspects iron homeostasis dysregulated different conditions will provide insights causes iron accumulation iron mediated tissue damage recent advances irondependent lipid peroxidation leading cell death called ferroptosis provided useful insights highly relevant lipid rich environment cnscritical issues review examines mechanisms control normal cellular iron homeostasis dysregulation mechanisms neurological disorders recent work iron can induce tissue damage via ferroptosisfuture directions quick reliable tests needed determine ferroptosis contributes pathogenesis neurological disorders addition need develop better drugable agents scavenge lipid radicals reduce cns damage neurological conditions currently effective treatmentspmid34569265 doi101089 ars20210218,0.0
louis dumnil 18231890 surgeon pioneer neurology rev neurol paris 2021 sep 23s00353787 21 006688 doi 101016 jneurol202106011 online ahead printabstractlouisstanislas dumnil 18231890 surgeon normandy contemporary jeanmartin charcot 18251893 throughout career dumnil published annotated observations neurological pathologies one year guillaume duchenne de boulogne 18061875 reported case progressive muscular paralysis tongue soft palate lips added five cases progressive muscular atrophy 1867 together histological examinations showed atrophy anterior horns spinal cord charcot described amyotrophic lateral sclerosis fail pay homage dumnil contribution 1862 dumnil added clinical observations progressive locomotor ataxia one first included anatomopathological examinations thus significantly completing clinical picture presented duchenne 1858 confirmed damage roots posterior tracts spinal cord finally providing multiple observations syndrome described octave landry 18261865 1859 contributed clinical picture acute ascending paralysis come us guillainbarr syndrome mention perspicacious physicians previous century already perfectly recognised disease finally augusta dejerineklumpke 18591927 paid warm tribute dumnil 1889 thesis calling one pioneers understanding individuality autonomy peripheral nervous system indeed pioneer although often overlookedpmid34565621 doi101016 jneurol202106011,0.0
cgasstingmediated ifni response host defense neuroinflammatory diseases curr neuropharmacol 2021 sep 24 doi 102174 1570159x19666210924110144 online ahead printabstractthe presence foreign misplaced nucleic acids danger signal triggers innate immune responses activating cytosolic dna sensor cyclic gmpamp synthase cgas binding downstream signaling effector stimulator interferon genes sting cgassting pathway activation links nucleic acid sensing immune responses pathogenic entities clearance however overactivation signaling pathway leads fatal immune disorders contributes progression many human inflammatory diseases therefore optimal activation pathway crucial elimination invading pathogens maintenance immune homeostasis review will summarize fundamental roles initiating host defense invading pathogens discuss pathogenic roles multiple neuroinflammatory diseases alzheimers disease ad parkinsons disease pd huntingtons disease hd amyotrophic lateral sclerosis als multiple sclerosis ms neurodegenerative diseasespmid34561985 doi102174 1570159x19666210924110144,0.0
differential effects fingolimod natalizumab magnetic resonance imaging measures relapsingremitting multiple sclerosis neurotherapeutics 2021 sep 24 doi 101007 s13311021011182 online ahead printabstractfingolimod natalizumab approved diseasemodifying drugs relapsingremitting multiple sclerosis rrms two drugs different modes action may therefore influence different aspects msrelated tissue damage retrospective cohort study longitudinally compared patients treated fingolimod patients treated natalizumab measures based structural magnetic resonance imaging mri included patients rrms given two standardized mri scans drug available interval least 6 months therapy start baseline scan baseline scan followup scan matching age baseline followup scans 93 patients fingolimod 48 natalizumab 45 investigated mean followup time 19 years determined number new white matter lesions well thalamic cortical wholebrain atrophy scaling time interscan interval measures analyzed group comparisons account demographic clinical characteristics multiple regression models binary logistic regression model compared natalizumab fingolimod treatment went along new white matter lesions median interquartile range iqr 00 00 07 vs 00 00 00 year p 001 whereas wholebrain atrophy lower median iqr 02 00 05 vs 05 02 10 year p 001 significant differences confirmed multiple regression models binary logistic regression model conclusion observation compatible stronger neuroprotective properties fingolimod compared natalizumabpmid34561843 doi101007 s13311021011182,1.0
multiple sclerosis genetic polymorphisms fibrinogenmediated hemostatic pathways casecontrol study neurol sci 2021 sep 24 doi 101007 s10072021056081 online ahead printabstractintroduction blood coagulation constituents might exert immunomodulatory functions cns may trigger neuroinflammation demyelination evaluated whether particular singlenucleotide polymorphisms snps thought involved fibrinogenmediated hemostatic pathways overrepresented patients ms compared controlsmethods casecontrol study consisted 119 ms patients recruited consecutively clinic 68 healthy controls afterwards created cumulative genetic risk score cgrs included 5 selected hemostatic risk alleles betafibrinogen 455g glycoprotein iiia p1a2 factor v leiden factor v h2r prothrombin 20210g multivariate ordinal logistic regression multivariate multinomial logistic regression applied evaluate effect cgrs ms susceptibilityresults fgb 455 g factor v h1299r variants might associated ms status recessive dominant model respectively cumulative association five snps investigated disease observeddiscussion found ms patients carried prohemostatic variants healthy controls increasing number unfavorable alleles might increase likelihood ms group cumulative analysis findings encourage evaluating variants larger populationbased cohortpmid34561786 doi101007 s10072021056081,1.0
visual function brief cognitive assessment multiple sclerosis optic neuritis clinically isolated syndrome patients j neuroophthalmol 2021 sep 23 doi 101097 wno0000000000001280 online ahead printabstractbackground study hypothesized clinically isolated syndromeoptic neuritis patients may disturbances neuropsychological functions related visual processesmethods fortytwo patients optic neuritis within 3 months onset 13 healthy controls assessed baseline 6 months mri brain volumes lesion load optic radiation lesion volume optical coherence tomography oct peripapillary retinal nerve fiber layer rnfl ganglion cell inner plexiform layers gcipls inner nuclear layer patients underwent brief cognitive assessment multiple sclerosis highcontrast lowcontrast letter acuity color visionresults baseline patients impaired visual function gcipl thinning eyes performed normative average visualrelated tests symbol digit modalities test brief visuospatial memory testrevised bvmtr time improvement visual function affected eye predicted baseline gcipl p 0015 rnfl decreased bvmtr improved p 0001 improvement bvmtr associated improvement highcontrast letter acuity affected eye p 003 independently oct mri metricsconclusion cognitive testing assessed binocularly visuospatial processing affected unilateral optic neuritis improves time visual recovery related structural markers visual central nervous systempmid34561401 doi101097 wno0000000000001280,0.0
fatigue selfmanagement education persons diseaserelated fatigue comprehensive review effectiveness fatigue quality life patient educ couns 2021 sep 14s07383991 21 00625x doi 101016 jpec202109016 online ahead printabstractobjectives systematically synthesize effectiveness fatigue selfmanagement education sme fatigue quality life qol persons diseaserelated fatigue describe intervention characteristicsmethods systematically reviewed literature smes people diseaserelated fatigue included randomized controlled trials rct aimed improve selfmanagement skills fatigue daily life synthesized effectiveness mapped intervention characteristicsresults included 26 rcts studying samples eight disease groups followup 46 studies reported statistically significant improvements fatigue 46 qol persons cancer 6 8 multiple sclerosis 8 10 rcts showed positive evidence favor sme range effect sizes wide d 00 08 delivery modalities inpatient outpatient home interactions individual group remote duration range h 1175 variedconclusions overall evidence effectiveness smes fatigue qol limited inconsistent persons cancer multiple sclerosis evidence provides positive effect rcts medium large effect qol indicate potential benefit smespractical implication duration peer interaction considered tailoring smes populations contextspmid34561143 doi101016 jpec202109016,0.0
brain oxygen extraction fraction mapping patients multiple sclerosis j cereb blood flow metab 2021 sep 24271678x211048031 doi 101177 0271678x211048031 online ahead printabstractwe aimed demonstrate feasibility whole brain oxygen extraction fraction oef mapping measuring lesion specific regional oef abnormalities multiple sclerosis ms patients 22 ms patients 11 healthy controls hc oef neural tissue susceptibility n maps computed mri multiecho gradient echo data ms patients 80 chronic active lesions hyperintense rim quantitative susceptibility mapping identified mean oef n within rim core compared using linear mixedeffect model analysis rim showed higher oef n core relative adjacent normal appearing white matter oef contrast 66 70 vs 98 78 p 0001 n contrast 339 203 ppb vs 257 205 ppb p 0017 ms hc oef n compared using linear regression model subjectbased regions interest whole brain compared hc ms lower oef 304 33 vs 214 44 p 0001 higher n 237 70 ppb vs 113 77 ppb p 0018 feasibility study suggests oef may serve useful quantitative marker tissue oxygen utilization mspmid34558996 doi101177 0271678x211048031,0.0
effect psychoeducation program based rational emotional behavioral approach individuals multiple sclerosis diagnosis randomized controlled trial perspect psychiatr care 2021 sep 23 doi 101111 ppc12949 online ahead printabstractpurpose study aimed examine effects psychoeducational program cognitive emotion regulation levels individuals multiple sclerosis ms design method study followed randomized controlled quasiexperimental design questionnaire including descriptive characteristics diseaserelated characteristics cognitive emotion regulation questionnaire used data collectionfindings difference pretestposttest followup test mean scores patients experimental group significant p 005 conclusion psychoeducation program based rational emotional behavioral approach increased use cognitive emotion regulation strategies individuals mspmid34558061 doi101111 ppc12949,0.0
depression anxiety fear covid19 patients multiple sclerosis pandemic era crosssectional study neurol sci 2021 sep 23 doi 101007 s10072021056125 online ahead printabstractbackground depression anxiety two important factors determining quality life patients multiple sclerosis pwms covid19 pandemic era several factors can provoke mental issues people patients crosssectional study aim estimate new prevalence anxious depressive symptoms relating factors pwmsmethods crosssectional study include pwms recruited ms clinic sina hospital tehran joined channel telegram media selfdesigned online questionnaire consisted 4 parts handed patients demographic clinical data beck depression inventory beck anxiety inventory fear covid19 scale univariate multiple logistic regression analyses performed find relating factors expression depressive anxious symptoms pwmsresults total 282 participants mean age 3566 307540 years suffering multiple sclerosis 736 310 years 817 women 691 classified relapsingremitting ms mean score bdi 1713 1151 classified minimalmoderate depressive symptoms 486 patients express depressive symptoms bdiii 14 others reported degrees depression univariate analysis employment p 0015 marital status p 0022 level education p 0004 number hospitalization due ms attacks p 0048 fear covid19 p 00001 associated significantly presence depressive symptoms entering factors binary logistic regression model level education p 0019 marital status p 0044 number hospital admissions due ms relapses 110 p 002 fear covid19 107 p 0001 remained significant relating factors mean score anxiety calculated 1454 975 just 32 patients severe anxiety employment p 0045 edss score p 0004 fear covid19 p 00001 reported relating anxious symptoms significantly univariate analysis entering logistic regression analysis edss 130 p 0001 fear covid19 113 p 00001 remained significant relating factors anxious symptomsconclusion overall prevalence depressive symptoms pwms ms clinic 514 obviously higher worlds centers due fear covid19 addition fear covid19 presence depressive symptoms pwms related significantly level education number hospital admissions due ms relapses marital status side patients classified suffering anxious symptoms severe problems fear covid19 recommended future studies compare patients score covid19 era score pandemicpmid34554334 doi101007 s10072021056125,0.0
predictors ocrelizumab effectiveness patients multiple sclerosis neurotherapeutics 2021 sep 22 doi 101007 s13311021011048 online ahead printabstractdata regarding effectiveness safety ocrelizumab postmarking setting lacking aim study provide effectiveness safety data ocrelizumab treatment patients relapsingremitting rr progressive multiple sclerosis pms evaluate clinical immunological predictors early treatment response singlecenter prospective observational study investigated effectiveness outcomes timetoconfirmed disability worsening timetofirst relapse timetofirst evidence mri activity timetofirst evidence disease activity clinical immunological predictors early treatment response incidence adverse events aes one hundred fiftythree subjects included 93 rrms 84 females median followup 19 1327 2year followup fu disability worseningfree survival 905 647 688 rrms primaryprogressive ms ppms secondaryprogressive ms spms patients respectively 2year fu 671 727 813 patients rrms ppms spms free mri activity neda3 percentages 621 546 551 respectively lower baseline edss independently associated reduced risk disability worsening hr 95ci 145 105200 p 0024 previous treatment exposure independently associated increased probability radiological activity hr 253 105610 p 0039 6month fu cd8 + cell decrease less pronounced patients inflammatory activity p 0022 six patients 39 discontinued ocrelizumab due severe aes findings suggest ocrelizumab effective treatment realworld patients rrms pms manageable safety profile better outcomes observed treatmentnave patients patients low baseline disability level depletion cd8 + cells underlie early therapeutic effects ocrelizumabpmid34553320 doi101007 s13311021011048,1.0
headache multiple sclerosis pharmacological aspects curr pharm des 2021 sep 22 doi 102174 1381612827666210922114100 online ahead printabstractfor decades headache considered typical symptom multiple sclerosis ms construed red flag important differential diagnoses cerebral vasculitis meanwhile several studies demonstrated increased prevalence headache ms compared general population due heterogeneity headache genesis frequent occurrence primary secondary headaches ms one hand ms migraine often comorbid hand secondary headaches occur frequently especially course ms relapses often migrainelike headaches caused inflammation can improve result msspecific therapy headaches particularly common early stages chronic inflammatory cns disease inflammatory activity greatest addition headache can also occur side effect diseasemodifying drugs dmds headache can occur dmds frequently described interferonbeta therapy aim work present prevalence headache describe heterogeneity possible causes headache ms addition important therapeutic aspects treatment ms patients general will presented well different approaches treatment headache ms depending etiological classificationpmid34551691 doi102174 1381612827666210922114100,0.0
association iron rim lesions brain cervical cord volume relapsing multiple sclerosis eur radiol 2021 sep 22 doi 101007 s0033002108233w online ahead printabstractobjectives multiple sclerosis ms iron rim lesions irls indicators chronic lowgrade inflammation ongoing tissue destruction aim study assess relationship irls clinical measures magnetic resonance imaging mri markers particular brain cervical cord volumemethods clinical mri parameters 102 relapsing ms patients relapses least 6 months contrastenhancing lesions included followup data obtained 12 months available 49 patients irls identified susceptibilityweighted images swis addition standard brain spinal cord mri parameters normalised crosssectional area ncsa upper cervical cord calculatedresults thirtyeight patients least one irl swi mri baseline patients irls higher edss scores higher lesion loads brain spinal cord lower cortical grey matter volumes lower ncsa followup brain atrophy rates higher patients irls irls correlated spatially t1hypointense lesionsconclusions relapsing ms patients irls showed aggressive mri disease characteristics crosssectional longitudinal analyseskey points multiple sclerosis patients iron rim lesions higher edss scores higher brain spinal cord lesion loads lower cortical grey matter volumes lower normalised crosssectional area upper cervical spinal cord iron rim lesions new lesion descriptor obtained susceptibilityweighted mri data suggests exploration lesion characteristic regard poorer prognosis multiple sclerosis patients warrantedpmid34549326 doi101007 s0033002108233w,0.0
modular deep neural networks automatic quality control retinal optical coherence tomography scans comput biol med 2021 sep 18104822 doi 101016 jcompbiomed2021104822 online ahead printabstractretinal optical coherence tomography oct intraretinal layer segmentation increasingly used ophthalmology also neurological diseases multiple sclerosis ms signal quality influences segmentation results highquality oct images needed accurate segmentation quantification subtle intraretinal layer changes among others oct image quality depends ability focus patient compliance operator skills current criteria oct quality define acceptable image quality depend manual rating experienced graders time consuming subjective paper propose validate standardized graderindependent realtime feedback system automatic quality assessment retinal oct images defined image quality criteria scan centering signal quality image completeness based published quality criteria typical artifacts identified experienced graders inspecting oct images trained modular neural networks oct data manual quality grading analyze image quality features quality analysis combination trained networks generates comprehensive quality report containing quantitative results validated approach quality assessment according oscarib criteria experienced grader 100 oct files volume circular radial scans centered optic nerve head macula analyzed classified specificity 096 sensitivity 097 accuracy 097 well matthews correlation coefficient 093 indicate high rate correct classification method shows promising results comparison manual oct grading may useful realtime image quality analysis analysis large data sets supporting standardized application image quality criteriapmid34548173 doi101016 jcompbiomed2021104822,0.0
association cholesterol 7alphahydroxylase cyp7a1 promoter polymorphism rs3808607 cholesterol 24shydroxylase cyp46a1 intron 2 polymorphism rs754203 serum lipids vitamin d levels multiple sclerosis risk turkish population neurol sci 2021 sep 21 doi 101007 s10072021055971 online ahead printabstractbackground patients multiple sclerosis ms significantly lower vitamin d levels cholesterol known precursor vitamin d synthesis cholesterol removal regulated cholesterol 7hydroxylase cyp7a1 liver cholesterol 24shydroxylase cyp46a1 brain study single nucleotide polymorphisms snps within genes cyp7a1 rs3808607 cyp46a1 rs754203 investigated effects serum lipid profiles vitamin d levels risk developing msmethods patients ms n 191 controls n 100 tested using pcrrflp method determine genotypes rs3808607 rs754203 snpsresults minor c allele frequency cyp7a1 rs3808607 variation 0380 patients ms 0305 control subjects p 074 cyp46a1 rs754203 frequencies minor c allele 0272 0250 patients control subjects respectively p 563 serum vitamin d 25 oh d3 concentrations significantly lower patients control subjects p 002 cyp46a1 rs754203 snp associated total cholesterol levels patients whereas cyp7a1 rs3808607 variant associated serum lipid parameters vitamin d levels patients control subjectsconclusion cyp7a1 rs3808607 cyp46a1 rs754203 variations likely confer independent risk ms development turkish population best knowledge first study investigate association cyp46a1 rs754203 ms riskpmid34546511 doi101007 s10072021055971,0.0
dry needling treatment muscle spasticity patient multiple sclerosis case report physiother theory pract 2021 sep 2117 doi 101080 0959398520211978118 online ahead printabstractbackground spasticity common cause disability multiple sclerosis ms can negatively affect patients walking balanceobjective evaluate immediate effect dry needling dn spasticity mobility female mscase description case 38yearold female 4year history ms treated hamstring muscles biceps femoris semitendinosus needled 1 minute single session main outcome measures modified modified ashworth scale mmas evaluate spasticity timed 25foot walk t25fw assessment mobility leg function performance stiffness biomechanical index spasticity measured dynamometer assessments done immediately dnoutcomes mmas scores decreased hamstrings 1 0 quadriceps 2 1 mobility improved time t25fw decreased 1630 929 seconds stiffness hamstring decreased treatment 0451 0312 conclusion one session dn hamstring muscle decreased spasticity improved mobility patient ms studies suggestedpmid34546842 doi101080 0959398520211978118,1.0
treatment options multiple sclerosis neuromyelitis optica spectrum disorders curr pharm des 2021 sep 20 doi 102174 1381612827666210920151231 online ahead printabstractthere diseases many therapeutic advances recent years multiple sclerosis nine different drug classes dozen approved therapies now available similarly unimaginable advances understanding neuromyelitis optica now neuromyelitis optica spectrum disorder nmosd past 15 years building knowledge gained first therapies approved recent years review aim present therapies approved treatment ms nmosd different forms application different approval criteria important side effects will presented work intended physicians interested ms nmosd therapies want get first overview replace respective guidelines regulatory authoritiespmid34544336 doi102174 1381612827666210920151231,0.0
potent t cell mediated antiinflammatory role selective cb2 agonist lenabasum multiple sclerosis neuropathol appl neurobiol 2021 sep 20 doi 101111 nan12768 online ahead printabstractbackground lenabasum synthetic cannabinoid receptor type2 cb2 agonist able exert potent antiinflammatory effects role t cells remains unknownobjectives present study undertaken investigate antiinflammatory mechanisms lenabasum t lymphocyte subsets vivo therapeutic efficacy experimental autoimmune encephalomyelitis eae methods mononuclear cells 17 healthy subjects hs 25 relapsingremitting multiple sclerosis rrms patients activated presence absence lenabasum analysed flow cytometry qrtpcr eae mice treated lenabasum clinical score neuroinflammation evaluatedresults lenabasum significantly reduced tnfa production cd4+ t cells cd8+ t cells dosedependent manner hs rrms patients ms patients lenabasum also reduced activation marker cd25 inhibited il2 production t cell subsets ifn il17 committed th1 th17 cells respectively effects blocked pretreatment selective cb2 inverse agonist sr144528 vivo treatment eae mice lenabasum significantly ameliorated disease severity reduced neuroinflammation demyelination spinal cordconclusion lenabasum exerts potent t cellmediated immunomodulatory effects suggesting cb2 promising pharmacological target counteract neuroinflammation mspmid34543449 doi101111 nan12768,1.0
propagating uncertainty across cascaded medical imaging tasks improved deep learning inference ieee trans med imaging 2021 sep 20 pp doi 101109 tmi20213114097 online ahead printabstractalthough deep networks shown perform well variety medical imaging tasks inference presence pathology presents several challenges common models challenges impede integration deep learning models real clinical workflows customary process cascading deterministic outputs sequence imagebased inference steps eg registration segmentation generally leads accumulation errors impacts accuracy downstream inference tasks paper propose embedding uncertainty estimates across cascaded inference tasks performance downstream inference tasks improved demonstrate effectiveness proposed approach three different clinical contexts demonstrate propagating t2 weighted lesion segmentation results associated uncertainties subsequent t2 lesion detection performance improved evaluated proprietary largescale multisite clinical trial dataset acquired patients multiple sclerosis ii show improvement brain tumour segmentation performance uncertainty map associated synthesised missing mr volume provided additional input followup brain tumour segmentation network evaluated publicly available brats2018 dataset iii show propagating uncertainties voxellevel hippocampus segmentation task subsequent regression alzheimers disease clinical score improvedpmid34543193 doi101109 tmi20213114097,0.0
assessment artificial intelligence automatic multiple sclerosis lesion delineation tool clinical use clin neuroradiol 2021 sep 20 doi 101007 s0006202101089z online ahead printabstractpurpose implement validate existing algorithm automatic delineation white matter lesions magnetic resonance imaging mri patients multiple sclerosis ms local singlecenter datasetmethods implemented white matter hyperintensity segmentation model based 2d convolutional neural network using conventional t2weighted fluid attenuated inversion recovery flair mri sequence input model adapted delineation ms lesions training local dataset 93 ms patients total 3040 lesions quantitative evaluation performed ten test patients modelgenerated masks compared manually delineated masks two expert delineators subsequent qualitative evaluation implemented model performed two expert delineators generated delineation masks clinical dataset 53 patients rated acceptable 10 errors unacceptable 10 errors based total number true lesionsresults quantitative evaluation resulted average accuracy score f1 071 recall 077 dice similarity coefficient 062 implemented model obtained highest scores three metrics compared three box lesion segmentation models clinical evaluation average 94 53 modelgenerated masks rated acceptableconclusion adaptation local dataset implemented segmentation model able delineate ms lesions high clinical value rated delineation experts outperforming popular box applications serves promising step towards implementation automatic lesion delineation ms clinicpmid34542644 doi101007 s0006202101089z,0.0
microrna22 level patients multiple sclerosis relationship vitamin d vitamin d receptor levels neuroimmunomodulation 2021 sep 1717 doi 101159 000519012 online ahead printabstractintroduction multiple sclerosis ms known multifactorial disorder numerous observational studies suggested implication multiple genetic environmental factors pathogenesis ms aim work evaluate expression microrna22 mirna22 level relation vitamin d vd vd receptor vdr levels patients ms remission statemethods casecontrol study conducted 50 patients clinically definite ms 50 age sexmatched healthy controls mirna22 expression assessed ms patients controls using quantitative rtpcr serum level vd vdr assessed ms patients controls using elisa techniquesresults mirna22 level significantly downregulated ms patients comparison controls p value 0001 ms patients also significantly lower vd vdr levels comparison controls p value 0001 0001 respectively patients secondary progressive ms spms significantly higher mirna22 level patients relapsing remitting ms rrms p value 0042 statistically significant positive correlation mirna22 level edss p value 0033 also statistically significant positive correlation mirna22 level vdr level p value 0002 conclusion mirna22 level significantly downregulated ms patients positive correlation disability status patients spms significantly higher mirna22 level patients rrms vd vdr levels significantly lower ms patients controls mirna22 level positively correlated vdr levelpmid34537762 doi101159 000519012,0.0
confisep impact covid19 pandemic lockdown patients multiple sclerosis north france rev neurol paris 2021 sep 11s00353787 21 006512 doi 101016 jneurol202109001 online ahead printabstractwe performed online survey assess lockdown impact 176 patients multiple sclerosis pwms north france access healthcare reduced 38 pwms mainly physiotherapy general practitioners neurologists 492 implemented selfrehabilitation programs medical support maintained 392 teleconsultations 762 reported negative impact lockdown related worsen disability 455 expressed beneficial effects like strengthening family relationships reduced fatigue previous studies found results disability discontinuation care however even period challenging pwms shown excellent adaptabilitypmid34538668 doi101016 jneurol202109001,0.0
reliability revised cochrane riskofbias tool randomised trials rob2 improved use implementation instruction j clin epidemiol 2021 sep 16s08954356 21 003073 doi 101016 jjclinepi202109021 online ahead printabstractobjective assess interrater reliability irr revised cochrane riskofbias tool randomised trials rob2 methods four raters independently applied rob2 critical important outcomes individually randomized parallelgroup trials rcts included cochrane review cannabis cannabinoids people multiple sclerosis calculated fleiss kappa multiple raters time complete tool performed calibration exercise five studies developed implementation document id specific condition intervention addressed review instructions answer signalling questions rob2 tool measured irr id adoption results 80 results related 7 outcomes 16 rcts assessed calibration exercise reached agreement overall judgment irr 015 irr individual domains ranged agreement fair mean time apply tool 1685 minutes per study time complete calibration exercise develop id 40 hours id adoption id overall agreement increased slightly irr 011 first 5 studies moderate irr 042 remaining 11 irr individual domains ranged agreement almost perfect mean time apply tool decreased 41 minutesconclusions rob2 tool comprehensive complex even high experienced raters development id specific review may improve reliability substantiallypmid34537386 doi101016 jjclinepi202109021,0.0
biological sex critical variable cd4+ effector t cell function preclinical models multiple sclerosis antioxid redox signal 2021 sep 20 doi 101089 ars20210202 online ahead printabstractt cells play pivotal role maintaining adaptive immune responses pathogens however misdirected t cell responses selftissues may lead autoimmune disease biological sex profound effects t cell function important determinant disease incidence severity autoimmune diseases multiple sclerosis ms many autoimmune diseases skew towards higher female incidence including ms however become increasingly accepted men living ms prone developing progressive disease course worsened disease outcomes review discuss known role biological sex t cell development differentiation examining evidence male sex can augment t helper 17 th17 responses next outline known sex differences animal models ms distinct roles played sex hormones versus sex chromosomes pathogenesis models finally will discuss recent advances examine molecular basis worsened disease outcomes males particular focus role played th17 cells modelspmid34538129 doi101089 ars20210202,0.0
exercise sports science australia essa position statement exercise people mild moderate multiple sclerosis j sci med sport 2021 aug 24s14402440 21 002140 doi 101016 jjsams202108015 online ahead printabstractobjectives multiple sclerosis ms common chronic progressive neurological condition central nervous system affects 26 000 australian adults exercise training beneficial effects msrelated impairments including reduced muscular strength poor aerobic capacity impaired mobility consequence can improve quality life position statement provides evidencebased recommendations exercise prescription delivery exercise training people ms mild moderate disabilitydesign methods synthesis published works within field exercise training msresults exercise provides many benefits people ms strong evidence resistance aerobic training performed 2 3 times per week moderate intensity safe can improve muscle strength cardiorespiratory fitness balance fatigue functional capacity mobility quality life people ms mild moderate disability expanded disease severity scale edss 65 however evidence severe disability edss 65 less clear effects exercise ms pathogenesis central nervous structures outcomes depression cognitive impairment adequately investigated effective exercise interventions improve balance joint contractures reduce falls people ms also urgently needed well investigations longterm 1 year effects exercise trainingconclusions resistance aerobic training exercises effective alleviate characteristic signs symptoms ms supplemented balance exercise prevent falls exercise training programs prescribed delivered qualified exercise professionals important recognise accommodate exerciseassociated complications fatigue heat sensitivitypmid34538565 doi101016 jjsams202108015,0.0
analysis patients#39 access reimbursed biotechnological medicines multiple sclerosis bulgaria greece expert rev pharmacoecon outcomes res 2021 sep 16 doi 101080 1473716720211981134 online ahead printabstractobjective goal perform comparative analysis multiple sclerosis patients access medicines bulgaria greecematerials methods comparative analysis pharmaceutical legislation bulgaria greece focusing medicines multiple sclerosis ms performed patients access therapy assessed guideline compliance index gci availability indexresults procedures marketing authorization pricing reimbursement inclusion medicines positive drug list pdl identical european union member states almost ms medicines authorized sale european union included bulgarian greek pdl pdls included medicines different groups immunostimulants immunostimulants immunosuppressors selective immunosuppressors immunosuppressors medicines fully paid health insurance funds countries average time inclusion medicines ms pdl bulgaria marketing authorization 3 years analysis pharmacotherapeutic guidelines showed high gci higher bulgaria 0846 vs 0769 1conclusions existing legislative measures national level bulgaria greece ensure adequate timely access patients ms treatmentpmid34525887 doi101080 1473716720211981134,0.0
ackr1 favors transcellular paracellular tcell diapedesis across bloodbrain barrier neuroinflammation vitro eur j immunol 2021 sep 15 doi 101002 eji202149238 online ahead printabstractthe migration cd4+ effector memory t cells across bloodbrain barrier bbb critical step multiple sclerosis animal model experimental autoimmune encephalomyelitis eae tcell diapedesis across bbb can occur paracellular via complex bbb tight junctions transcellular via pore brain endothelial cell body making use primary mouse brain microvascular endothelial cells pmbmecs vitro model bbb directly compared transcriptome profile pmbmecs favoring transcellular paracellular tcell diapedesis rna sequencing rnaseq identified atypical chemokine receptor 1 ackr1 one main candidate genes upregulated pmbmecs favoring transcellular tcell diapedesis confirmed upregulation ackr1 protein pmbmecs promoting transcellular tcell diapedesis venular endothelial cells cns eae lack endothelial ackr1 reduced transcellular tcell diapedesis across pmbmecs physiological flow vitro combining previous observation endothelial ackr1 contributes eae pathogenesis shuttling chemokines across bbb present data supports ackr1 mediated chemokine shuttling enhances transcellular tcell diapedesis across bbb autoimmune neuroinflammation article protected copyright rights reservedpmid34524684 doi101002 eji202149238,0.0
patient caregiver health state utilities tuberous sclerosis complex pharmacoecon open 2021 sep 15 doi 101007 s41669021002961 online ahead printabstractbackground tuberous sclerosis complex tsc rare multisystem disorder often associated treatmentresistant epilepsy costeffectiveness analysis new antiseizure medications typically requires health state utilities hsus reflect burden given conditionobjective study aimed estimate hsus focus valuing impact seizure type seizure frequency healthrelated quality life hrql patients tsc caregiversmethods targeted literature review qualitative research healthcare professionals caregivers informed development health state vignettes describing experience living tsc caring child tsc vignettes evaluated interviews uk general population using time tradeoff tto methodresults sixteen vignettes developed describing patient hrql n 8 caregiver hrql n 8 two hundred interviews conducted via online video calls due covid19 pandemic restrictions two hundred participants evaluated patient n 100 caregiver n 100 health state vignettes estimated utility scores varied consistently according seizure type seizure frequency patient tto utility scores ranged 0234 highest seizure frequency multiple seizure types 0725 seizurefree state caregiver tto utility scores ranged 0221 0905conclusions findings highlight substantial burden living tsc caring child tsc patient caregiver burden greater generalised versus focal seizures burden greatest combination seizure types worsened increasing seizure frequencypmid34524653 doi101007 s41669021002961,0.0
identification causal metabolites related multiple autoimmune diseases hum mol genet 2021 sep 15ddab273 doi 101093 hmg ddab273 online ahead printabstractobject observational studies provide evidence metabolites may involved development autoimmune diseases ads whether causal still unknownmethods based largescale gwas summary statistics twosample mendelian randomization mr performed evaluate causal association human serum metabolites multiple ads inflammatory bowel disease ibd ulcerative colitis uc crohns disease cd rheumatoid arthritis ra systemic lupus erythematosus sle type 1 diabetes t1d multiple sclerosis ms primary biliary cirrhosis pbc primary sclerosing cholangitis psc comprehensive sensitive analysis used validate robustness mr results multivariable mr analysis conducted avoid potential pleiotropic effect complex traits finally metabolic pathway analysis performed based causal metabolites ad respectivelyresults identified 6 causal features metabolite bonferroni adjustment ie glycerol 2phosphate t1d hexadecanedioate phenylacetylglutamine laurylcarnitine ra glycine arachidonate 204n6 cd comprehensively sensitive analysis proved robustness causal associations also observed overlaps metabolites among different ads indicating similar mechanisms controlling several common traits multivariable mr analysis ruled potential pleiotropic effects validated independence identified metabolites additionally total 6 metabolic pathways identified different adsconclusions study provided novel insights investigating causal role serum metabolites development multiple ads comprehensive genetic pathwaypmid34523675 doi101093 hmg ddab273,0.0
ratedependent depression impaired amyotrophic lateral sclerosis neurol sci 2021 sep 13 doi 101007 s10072021055962 online ahead printabstractobjective investigated ratedependent depression rdd hoffman reflex hreflex patients amyotrophic lateral sclerosis als degenerative disease ventral horn involvementpatients methods casecontrol study enrolled 27 patients als 30 matched healthy control subjects clinical electrophysiological assessments well rdd response various stimulation frequencies 05 hz 1 hz 3 hz 5 hz compared groups multiple clinical electrophysiological factors also explored determine underlying associations rddresults als group showed significant loss rdd across frequencies compared control group notably following 1 hz stimulation 191 203 vs 340 137 p 0003 among factors might influence rdd enlargement motor unit potential mup showed significant relationship rdd following multifactor analysis variance p 0007 pearson correlation analysis 070 p 0001 various upper motor neuron manifestations correlated rdd values p 005 conclusion report loss rdd patients als strong correlation detected rdd deficit increased mup suggests rdd sensitive indicator underlying spinal disinhibition alstrial registration chictr2000038848 10 7 2020 retrospectively registered http wwwchictrorgcn pmid34518934 doi101007 s10072021055962,0.0
evaluation unidimensional fatigue impact scale ufis crohn#39 s disease importance local item dependency j nurs meas 2021 sep 13jnmd2000116 doi 101891 jnmd2000116 online ahead printabstractbackground purpose unidimensional fatigue impact scale ufis developed use multiple sclerosis population aim determine whether ufis valid tool measuring impact fatigue crohns disease cd method cd patients completed ufis part validation study crohns life impact questionnaire cliq data analyzed according rasch measurement theory rmt results two hundred sixtyone completed ufis questionnaires available analysis rescoring items resolve disordered thresholds 22 items showed acceptable rmt fit however considerable local item dependency lid conclusion ufis provide unidimensional measurement sample cd patients due high levels lid combining three fis outcomes single measure justifiedpmid34518414 doi101891 jnmd2000116,0.0
good activity indices systemic sclerosis curr rheumatol rev 2021 sep 12 doi 102174 1573397117666210913102759 online ahead printabstractbackground fully validated index available assessing overall disease activity systemic sclerosis ssc objectives estimate effect disease activity measured different disease activity indices risk subsequent organ damagemethods european systemic sclerosis study group activity index escsg ai european scleroderma trials research group activity index reustar ai 12 point activity index proposed minier 12point ai calculated 91 patients criss composite response index systemic sclerosis patients included 2016 data analysed parametric nonparametric tests logistic regressionresults escsg ai reustar ai 12point ai correlated lung involvement escsg ai reustar ai correlated diffuse skin involvement escsg ai correlated digital ulcers diffuse cutaneous involvement reustar ai renal crisis bivariate analysis showed inverse correlation three disease activity scores forced vital capacity fvc p0001 diffusing capacity carbon monoxide dlco p0001 positive correlation pulmonary fibrosis p0001 modified rodnan skin score mrss p0001 health assessment questionnaire haq p0001 systolic pulmonary pressure spap p0001 creactive protein crp p0001 capillaroscopy scoring p0001 baseline visit 3year followup visit logistic regression revealed baseline escsg ai adjusted gender age baseline 12point ai adjusted unadjusted predicted worse skin involvement 3year followup adjusted escsg ai predicted decreasing dlco also 12point ai predicted decline fvc higher haq scores 3year follow baseline reustar ai able predict muscular deterioration decline fvc increase haq score 3 years following active disease according escsg ai first visit predicted progression joint involvement active disease baseline showed reustar ai predicted muscular deterioration fvc dlco worsening well increasing haq score followup period reustar ai score predict decrease fvc multiple regression prediction model 1306 1025 1665 p031 baseline escsg ai best predicted worsening dlco or1749 1104 2772 p0017 conclusion study establish gold standard assess disease activity ssc especially escsg ai reustar ai quantify predict major organ involvement daily practice criss can useful outcome measure patients short disease duration included clinical studiespmid34517805 doi102174 1573397117666210913102759,0.0
frequency diencephalic syndrome nmosd acta neurol belg 2021 sep 13 doi 101007 s13760021017921 online ahead printabstractbackground diencephalic region brain harbors sites considerable amount aquaporin4 expression neuromyelitis optica spectrum disorder nmosd primarily involves autoimmune processes molecule however little known frequency symptoms diencephalic involvement nmosd patientsobjective investigate frequency symptoms diencephalic involvement nmosd patients describe associated characteristics patients presenting symptomsmaterials methods retrospective cohort included 145 nmosd patients 39 males 106 females visited isfahan multiple sclerosis center january 2013 february 2020 approximately 61 months demographic clinical information patients findings radiological serological investigations retrievedresults frequency diencephalic involvement nmosd patients 34 five cases diencephalic syndromeassociated symptoms observed cohort consisted narcolepsy n 2 40 hypotension n 1 20 amenorrhea n 1 20 syndrome inappropriate antidiuretic hormone secretion n 1 20 manifestations responded well nmosdassociated treatments ie rituximab azathioprineconclusion although rarely manifested symptoms suggestive diencephalic involvement nmosd considered encountering patients diencephalic syndrome identify primary cause manifestationspmid34515964 doi101007 s13760021017921,0.0
role adenosine receptors rare neurodegenerative diseases motor symptoms curr protein pept sci 2021 sep 9 doi 102174 1389203722666210910110126 online ahead printabstractthe approval istradefylline adenosine 2a receptor a2ar antagonist addon treatment adult patients parkinsons disease food drug administration fda european medicines agency ema latest proof importance adenosinergic system nervous system adenosine endogenous purine nucleoside role modulator neurotransmission inflammatory response expression pattern 4 adenosine receptors a1r a2ar a2br a3r extracellular adenosine levels attracted great interest pathogenesis possible treatment rare neurodegenerative diseases motor symptoms include huntingtons disease hd amyotrophic lateral sclerosis als multiple sclerosis ms restless legs syndrome rls machadojoseph disease mjd also known spinocerebellar ataxia type 3 sca3 review shall focus role different adenosine receptor subtypes development possible treatment aforementioned rare neurodegenerative diseases motor symptoms using currently available data last section discusses possibility role adenosine receptors treatment rare diseases based available molecular pathology knowledgepmid34514988 doi102174 1389203722666210910110126,0.0
considerations regarding noncredible performance neuropsychological assessment patients multiple sclerosis case series appl neuropsychol adult 2021 sep 11110 doi 101080 2327909520211971229 online ahead printabstractdetermining validity data clinical neuropsychological assessment crucial proper interpretation extensive literature emphasized myriad methods diverse samples however little research considered noncredible presentation persons multiple sclerosis pwms pwms often experience one factors known impact validity data including major neurocognitive impairment psychological distress psychogenic interference secondary gain case series aimed illustrate potential relationships factors performance validity testing pwms six cases irbapproved database containing pwms referred neuropsychological assessment large academic medical center involving least one abovestated factors identified backgrounds neuropsychological test data clinical considerations reviewed interestingly pwms diagnosed major neurocognitive impairment found noncredible performance patient noncredible performance absence notable psychological distress given variability noncredible performance multiplicity factors affecting performance validity pwms clinicians strongly encouraged consider psychometrically appropriate methods evaluating validity cognitive data pwms additional research aiming elucidate base rates mechanisms begetting methods assessing noncredible performance pwms imperativepmid34514920 doi101080 2327909520211971229,0.0
effect exercise fatigue multiple sclerosis network metaanalysis comparing different types exercise arch phys med rehabil 2021 sep 9s00039993 21 014179 doi 101016 japmr202108008 online ahead printabstractobjective network metaanalysis nma current evidence conducted determine physical exercise positive influence multiple sclerosis ms fatigue type exercise largest effect fatigue also according disease severitydata sources medline embase sportdiscus pedro cochrane library web science search strategy combined relevant terms related multiple sclerosis b clinical trials c exercise d fatigue inception february 2021study selection randomized controlled trials concerning effectiveness different types exercise total physical fatigue people ms includeddata extraction data extracted predesigned data extraction tables risk bias evaluated cochrane risk bias tool rob 20 evaluate quality evidence grading recommendations assessment development evaluation tool useddata synthesis total 58 studies examined data pooled using random effects model ranking seven eight different exercise interventions physical total fatigue scores respectively achieved highest effects pairwise comparisons combined exercise resistance training versus control ranging 074 124 nma combined exercise 151 95 ci 201 101 resistance training 115 95 ci 181 049 compared control group achieved highest effects physical total fatigue respectivelyconclusion exercise considered effective fatigue management strategy among different exercise modalities combined exercise effective exercise modality improving physical total fatigue resistance training also effective exercise total fatigue among people diagnosed mspmid34509464 doi101016 japmr202108008,1.0
acute disseminated encephalomyelitis fet pet#x2f mr clin nucl med 2021 sep 8 doi 101097 rlu0000000000003879 online ahead printabstractafter 3 weeks daily headache 28yearold otherwise healthy woman admitted emergency department firsttime generalized seizure ct showed left frontal mass perifocal edema brain mri raised suspicion cerebral lymphoma cerebrospinal fluid analysis revealed mononuclear pleocytosis 14 cells l without malignant cells normal protein levels absence oligoclonal bands fet pet mri lesion showed fet characteristics inflammatory disease acute disseminated encephalomyelitis suggested diagnosis final histopathological results brain biopsy confirmed acute disseminated encephalomyelitispmid34507326 doi101097 rlu0000000000003879,0.0
role cognitive impairment physical therapy attendance outcomes multiple sclerosis j neurol phys ther 2021 sep 9 doi 101097 npt0000000000000375 online ahead printabstractbackground purpose many persons multiple sclerosis pwms experience cognitive impairments may affect ability engage physical therapy limited information cognitive impairments associated pwms ability participate improve functional outcomes study aimed assess relationship cognitive functioning pwms attendance total goal attainment functional improvement following physical therapy interventionmethods participants n 45 pwms participated larger selfmanagement study enrolled physical therapy within past 2 years objective cognitive functioning examined using tests prospective memory retrospective memory working memory processing speed along selfreport measure bivariate analyses conducted examine relationship cognitive functioning physical therapy outcome session attendance attaining goals changes functional outcome measures followed logistic regressions age education gender disability level covariatesresults difficulty learning new verbal information associated greater likelihood showing one physical therapy sessions reductions working memory processing speed associated pwms meeting rehabilitation goals despite deficits new learning memory processing speed 852 pre postscores showed improvements least one functional outcome measure following physical therapy interventiondiscussion conclusions findings demonstrate ability pwms make functional motor gains despite presence cognitive impairments highlight potential contributions cognitive functioning attendance goal attainment physical therapy interventionvideo abstract available insights authors see video supplemental digital content 1 available http linkslwwcom jnpt a362 includes background methods results discussion authors voices pmid34507342 doi101097 npt0000000000000375,0.0
serum ifn2 measured singlemolecule array associates systemic disease manifestations sjgren#39 s syndrome rheumatology oxford 2021 sep 10keab688 doi 101093 rheumatology keab688 online ahead printabstractobjectives type ifn ifni activation prominent feature primary ss pss sle ssc ultrasensitive singlemolecule array simoa technology facilitated measurement subfemtomolar concentrations ifns aimed measure ifn2 serum pss sle ssc using simoa immunoassay correlate levels blood ifnstimulated gene isg expression disease activitymethods serum ifn2 measured patients pss n 85 n 110 sle n 24 ssc n 23 healthy controls hc n 68 using ifn simoa assay hdx analyser ifni pathway activation additionally determined serum ifni reporter assay paired samples whole blood isg expression ifi44 ifi44l ifit1 ifit3 mxa rtpcr mxaelisaresults serum ifn2 levels elevated pss median613 fg ml compared hc median 5 fg ml p 0001 ssc median116 fg ml p 0043 lower compared sle median3135 fg ml p 0068 positively correlated blood isg expression r 066094 p 0001 comparable mxaelisa auc093 ifn2 measurement using simoa identified pss high isg expression auc090 8093 specificity 7184 sensitivity blinded validation independent pss cohort yielded comparable accuracy multiple regression indicated independent associations autoantibodies igg hcq treatment cutaneous disease history extraglandular manifestations serum ifn2 concentrations pssconclusion thus simoa serum ifn2 reflects blood isg expression pss sle ssc light ifntargeting treatments simoa potentially applied patient stratification retrospective analysis historical cohortspmid34505866 doi101093 rheumatology keab688,0.0
intracortical surfacebased mr diffusivity investigate neurologic psychiatric disorders review j neuroimaging 2021 sep 10 doi 101111 jon12930 online ahead printabstractdiffusion tensor imaging dti allows quantification water diffusivity within cerebral cortex alterations cortical mean diffusivity md suggested reflect microstructural damage interestingly microstructural changes can detected absence macrostructural alterations cortical thinning gray matter volume loss however volumebased neuroimaging techniques study cortical md shown limitations terms intersubject registration partial volume correction smoothing artifacts review summarize surfacebased approach assessment intracortical md overcome technical limitations also provided important contributions fields neurology psychiatry since proposal 2018 use neuroimaging technique revealed cortical microstructural alterations wide range clinical contexts including alzheimers disease parkinsons disease schizophrenia huntingtons disease multiple sclerosis amyotrophic lateral sclerosis primary progressive aphasia cases detection early intracortical md alterations preceded identification macrostructural changes importantly microstructural damage significantly correlated cognitive performance biomarker measures suggesting potential role use clinical trials sensitive imaging marker neurodegeneration given dti widely available imaging modality encouraging results motivate research using novel neuroimaging metric clinical contexts overall technique shed light key role early cortical degeneration many diseases cortical involvement previously thought limited clinical biological significancepmid34506674 doi101111 jon12930,0.0
current uses emerging applications clinical integration artificial intelligence neuroradiology rev neurosci 2021 sep 10 doi 101515 revneuro20210101 online ahead printabstractartificial intelligence ai branch computer science variety subfields techniques exploited serve deductive tool performs tasks originally requiring human cognition ai tools subdomains incorporated healthcare delivery improvement medical data interpretation encompassing clinical management diagnostics prognostic outcomes field neuroradiology ai manifested deep machine learning connected neural networks cnns demonstrated incredible accuracy identifying pathology aiding diagnosis prognostication several areas neurology neurosurgery literature review survey available clinical data highlighting utilization ai field neuroradiology across multiple neurological neurosurgical subspecialties addition discuss emerging role ai neuroradiology strengths limitations well future needs strengthening role clinical practice review evaluated data across several subspecialties neurology neurosurgery including vascular neurology spinal pathology traumatic brain injury tbi neurooncology multiple sclerosis alzheimers disease epilepsy ai established strong presence within realm neuroradiology successful largely supportive technology aiding interpretation diagnosis even prognostication various pathologies research warranted establish full scientific validity determine maximum potential aid optimizing providing accurate imaging interpretationpmid34506699 doi101515 revneuro20210101,0.0
comparative effectiveness dimethyl fumarate multiple sclerosis br j clin pharmacol 2021 sep 9 doi 101111 bcp15071 online ahead printabstractobjectives assess effectiveness dimethyl fumarate dmf annual rate relapse subject treatment arrt disability progression multiple sclerosis ms compared injectable immunomodulators imm teriflunomide teri fingolimob fty real life settingmethods populationbased cohort study conducted using data french nationwide claims database snds patients initiating imm teri fty dmf july 1 2015 december 12 2017 45 years database history 1 35 years followup included study dmf patients 11 matched imm teri fty using high dimensional propensity score negative binomial regression logistic regression models used estimate relative risk rr 95 ci arrt odds ratio 95 ci disability progression respectivelyresults overall 9 304 subjects identified 290 initiated dmf 332 teri 56 fty 322 imm matched cohorts consisted 1779 dmf imm patients 1679 dmfteri patients 376 dmffty patients dmf significantly reduced arrt compared imm rr 072 061086 teri 081 068096 show significant difference compared fty risk progression ms specific disability significantly different matched cohortsinterpretation dmf associated lower risk treated relapse patients rrms firstline rrms agents teri iim pmid34505304 doi101111 bcp15071,0.0
role mitochondrial genes neurodegenerative disorders curr neuropharmacol 2021 sep 8 doi 102174 1570159x19666210908163839 online ahead printabstractmitochondrial disorders clinically heterogeneous resulting nuclear gene mitochondrial mutations disturb mitochondrial functions dynamics lack evidence linking mtdna mutations neurodegenerative disorders mainly due absence noticeable neuropathological lesions postmortem samples review describes various gene mutations alzheimers disease parkinsons disease amyotrophic lateral sclerosis multiple sclerosis stroke abnormalities including pink1 parkin sod1 mutations seem reveal mitochondrial dysfunctions due either mtdna mutation deletion mechanism remains unclear depthpmid34503413 doi102174 1570159x19666210908163839,0.0
expression prognostic value mir146a mir155 turkish patients multiple sclerosis neurol res 2021 sep 1017 doi 101080 0161641220211975221 online ahead printabstractmultiple sclerosis ms inflammatory autoimmune demyelinating neurodegenerative disorder central nervous system interactions environmental factors predisposition genes determining genes appear involved etiology epigenetic mechanisms micrornamediated gene regulation can determine susceptibility severity autoimmune diseases therefore determine role mir146a mir155 ms developmental stages expression levels serum ms clinically isolated syndrome cis patients compared healthy controls present study expression levels mir146a mir155 assessed using quantitative realtime pcr blood samples 15 cis patients 61 relapsingremitting multiple sclerosis rrms patients alongside 32 healthy patients controls furthermore associations clinicopathologic variables patients also evaluated dysregulations found mir146a mir155 expressions rrmscontrol group rrms patients evaluated terms characteristics sex annual attack rate age diagnosis duration followup immunomodulatory treatments used significant differences observed however significant dysregulations identified mirna expression vitamin d level edss values number attacks roc curve analysis showed mir146a mir155 significant rrmscontrol group area curve auc possible mir146a may associated vitamin d deficiency disease disability mir155 may associated number attackspmid34503396 doi101080 0161641220211975221,1.0
mindfulnessbased interventions people multiple sclerosis systematic review metaaggregation qualitative research studies disabil rehabil 2021 sep 9115 doi 101080 0963828820211964622 online ahead printabstractpurpose mindfulnessbased interventions mbis effective treatments stress anxiety depression pwms however low adherence high attrition may limit effectiveness qualitative research can provide important insights mbi acceptability accessibility implementation systematic review metaaggregation evaluated qualitative research findings use mbis pwmsmethods systematic searches undertaken six major electronic databases studies using qualitative mixed methods included two reviewers screened data extracted critically appraised studies metaaggregation performed following joanna briggs institute approach extracting findings developing categories synthesizing findingsresults six eligible papers including 136 pwms included metaaggregation 136 findings extracted grouped 17 categories four synthesized findings 1 accessing mindfulness 2 sense belonging 3 experiencing mindfulness 4 making mindfulness relevant sustainable pwmsconclusions mbis pwms need take consideration disability can limit accessibility online mbis synchronous asynchronous appear acceptable alternatives traditional facetoface courses however pwms benefit shared mindful experiencing highlight mbi instructors crucial helping understand practice mindfulness involving pwms design delivery iterative refinement make mbis relevant taking partimplications rehabilitationboth facetoface online mindfulnessbased interventions mbis appear acceptable pwms ideally people offered choice training modalitypwms derive benefit undertaking mbis peers sense camaraderie belonging develop shared mindful experiencesinstructors delivering mbis pwms knowledgeable condition participants describe instructor key role helping practice mindfulness effectively context unpleasant experiences associated msmbis tailored pwms include precourse orientation session clearly articulate mindfulness practices can help ms provide wellorganized course materials large font size deliver individual mindfulness practices flexibly depending participant needpmid34498997 doi101080 0963828820211964622,0.0
male genital lichen sclerosus associated urological interventions microincontinence case series 21 patients clin exp dermatol 2021 aug 3 doi 101111 ced14869 online ahead printabstractbackground male genital lichen sclerosus mglsc acquired chronic inflammatory cutaneous disease associated significant morbidity squamous cell carcinoma penis consideration evidence suggests chronic exposure susceptible epithelium urinary occlusion foreskin likely pathomechanism mglsc never occurs men circumcised birth associated trauma instrumentation anatomical abnormalities eg frank hypospadia results microincontinenceaim describe 21 patients developed mglsc following urological diagnoses proceduresmethods conducted retrospective review patients diagnosis mglsc whose symptoms related urological procedures attended saw one authors cbb privately period juneoctober 2018results total 21 patients mean age 59 years identified referrals came local urology departments primary care extramural dermatology services patients uncircumcised men developed symptoms signs mglsc within 5 years following urological procedure examination 30 patients found damp penile skin due microincontinence 21 patients 10 undergone radical prostatectomy prostate cancer 4 diagnosis peyronie disease 4 undergone multiple cystoscopies urethroscopies 2 undergone surgery bladder neck 1 undergone implantation penile prosthesis treat erectile dysfunctionconclusion case series strengthens urinary occlusion hypothesis causation mglsc important recognize urological interventions can create incompetence naviculomeatal valve post voiding uncircumcised men creates risk factor mglsc previously present occlusion phenomenon koebnerization currently unelucidated epithelial susceptibility factors lead inflammation sclerosis cancer patients urologists aware possibilities preventative measures instituted eg adaptive voiding habits barrier protectionpmid34499360 doi101111 ced14869,0.0
incidence chronic immunemediated inflammatory diseases diagnosis kawasaki disease populationbased cohort study rheumatology oxford 2021 sep 8keab680 doi 101093 rheumatology keab680 online ahead printabstractobjectives kawasaki disease kda immunemediated vasculitis childhood multiorgan inflammation determined risk subsequent immunemediated inflammatory disease imid including arthritis type 1 diabetes inflammatory bowel disease ibd autoimmune liver disease ald primary sclerosing cholangitis psc multiple sclerosis ms methods conducted matched populationbased cohort study using health administrative data ontario canada children aged 18 years born 19912016 diagnosed kda n 3 753 matched 5 nonkda controls general population n 18 749 determined incidence imids resolution kda three 12month washout periods used exclude kdarelated symptomsresults elevated risk arthritis kda patients compared nonkda controls starting three months index date 1030 vs 127 per 100 000 personyears pys incidence rate ratio irr 807 95 ci 495132 hazard ratio hr 808 95 ci 495132 resulting overall incidence imids elevated kda patients 1751 vs 680 per 100 000 pys irr 258 95 ci 193343 hr 258 95 ci 194343 however increased risk diabetes ibd ald psc ms kda patients similar results observed using 12month washout periodconclusions children diagnosed kda increased risk arthritis following acute kda event imids health care providers monitor arthritis children following diagnosis kdapmid34498025 doi101093 rheumatology keab680,0.0
smoldering lesions ms like put rim neuroradiology 2021 sep 9 doi 101007 s00234021028000 online ahead printabstractpurpose multiple sclerosis ms chronic active smoldering white matter lesions presenting hypointense rims susceptibilityweighted imaging swi brain recognized important radiological feature aim work study prevalence paramagnetic rim lesions rls ms patients clinical setting assess differences demographic clinical variables regarding presence rlsmethods 3 t brain magnetic resonance mr studies performed ms patients july 2020 january 2021 reviewed patients rls assessed threedimensional 3d swi images t2 flair lesion load volume assessed demographic laboratory oligoclonal bands csf clinical data including functional status expanded disability status scale edss retrieved clinical filesresults 192 patients 113 59 presented least 1 rl rlpositive group mean rl count 481 ranging 1 37 significant difference number rls different types ms p 0858 regarding presence rls significant differences based gender p 0083 disease duration p 0520 treatment regime p 0326 edss score p 0103 associated t2 flair lesion load volumeconclusion swi rls frequently detected cohort regardless ms type t2 flair lesion load volume demographic features disease duration clinical score results suggest rls associated severe forms disease today rls can seen 3 t 3d swi although clinical standard sequence yet therefore considered additional helpful mr sequence diagnostic workup ms although studies warranted establish role rls prognostic markerspmid34498108 doi101007 s00234021028000,0.0
incidence prevalence disability associated neurological disorders italy 1990 2019 analysis based global burden disease study 2019 j neurol 2021 sep 8 doi 101007 s00415021107745 online ahead printabstractbackground neurological conditions highly prevalent disabling particular elderly italian population witnessed sharp ageing can thus expect rising trend incidence prevalence disability conditionsmethods relied global burden disease 2019 study extract italian data incidence prevalence years lived disability ylds referred broad set neurological disorders including brain nervous system cancers stroke encephalitis meningitis tetanus traumatic brain injury spinal cord injury assessed changes 1990 2019 counts agestandardized ratesresults prevalent conditions tensiontype headache migraine dementias whereas disabling migraine dementias traumatic brain injury ylds associated neurological conditions increased 225 decreased 23 agestandardized rates overall increase prevalence ylds counts stronger noncommunicable diseases onset old age compared young adultage onset ones trends opposite direction agestandardized rates taken accountconclusions increase ylds associated neurological conditions mostly due population ageing growth nevertheless lived disability consequence impact health systems increased actions needed improve outcome mitigate disability associated neurological conditions spanning among diagnosis treatment care pathways workplace interventionspmid34498172 doi101007 s00415021107745,0.0
cortical spinal sacral peripheral neuromodulations therapeutic approaches treatment lower urinary tract symptoms multiple sclerosis patients review neuromodulation 2021 sep 8 doi 101111 ner13525 online ahead printabstractintroduction multiple sclerosis ms often associated urological disorders mainly urinary incontinence retention management necessary improve patients quality life qol reduce potential urological complications besides classical treatments based mainly anticholinergics selfcatheterization several neuromodulation techniques tried recent years improve urinary disorders review aim providing overview neuromodulation electrostimulation approaches manage urinary symptoms ms patientsmaterials methods literature search using medline performed papers english describing effects neuromodulation ms patients consideredresults total 18 studies met inclusion criteria reviewed four related sacral neuromodulation snm seven percutaneous tibial nerve stimulation ptns six spinal cord stimulation scs one transcranial magnetic stimulation tms discussion ptns snm seem effective safe therapeutic options treating lower urinary tract symptoms ms patients principally case overactive bladder oab symptoms similarly also scs tms shown effective despite limited number patients small number studies found literature interestingly techniques effective even patients respond well conservative therapies anticholinergics furthermore given safety efficacy stimulations ptns considered firstline treatment oab ms patients also considering often preferred patients commonly used treatmentspmid34496454 doi101111 ner13525,0.0
functional roles curcumin astrocytes neurodegenerative diseases neuroimmunomodulation 2021 sep 8111 doi 101159 000517901 online ahead printabstractprogressive abnormality loss axons neurons central nervous system cns cause neurodegenerative diseases nds protein misfolding collection important pathological features nds astrocytes plentiful cells mammalian cns 2040 human brain several central functions maintenance health correct function cns astrocytes essential role preservation brain homeostasis surprising multifunctional cells implicated onset progression several nds thus become exciting target study nds almost 15 years revealed curcumin several therapeutic effects wide variety diseases treatment curcumin valuable ingredient present turmeric spice several essential roles including anticarcinogenic hepatoprotective thrombosuppressive cardioprotective antiarthritic antiinflammatory antioxidant chemopreventive chemotherapeutic antiinfectious furthermore curcumin can suppress inflammation promote angiogenesis treat diabetes pulmonary problems neurological dysfunction review effects curcumin astrocytes nds focus alzheimers disease parkinsons disease multiple scleroses huntingtons disease amyotrophic lateral sclerosispmid34496365 doi101159 000517901,0.0
primary mediastinal large bcell lymphoma blood 2021 sep 9blood2020008376 doi 101182 blood2020008376 online ahead printabstractprimary mediastinal large bcell lymphoma pmbcl separate entity classification based clinicopathologic features distinct molecular signature overlaps nodular sclerosis classical hodgkin lymphoma nschl molecular classifiers can distinguish pmbcl diffuse large bcell lymphoma dlbcl using rna derived paraffinembedded tissue integral future studies however given 5 dlbcl can molecular pmbcl phenotype absence mediastinal involvement clinical information will remain critical diagnosis studies last 1020 years elucidated biologic hallmarks pmbcl reminiscent chl including importance jakstat nfkb signaling pathways well immune evasion phenotype multiple converging genetic aberrations outcome pmbcl improved modern rituximab era however controversies remain whether single standard treatment patients integrate radiotherapy regardless frontline therapy refractory disease can occur 10 patients correlates poor outcome emerging data supporting high efficacy pd1 inhibitors pmbcl studies underway integrating upfront settingpmid34496020 doi101182 blood2020008376,0.0
splitting total dose cyclophosphamide two blocks apart conditioning autologous hematopoietic stem cell transplantation multiple sclerosis results diminished cardiotoxicity experience 1 000 patients rev invest clin 2021 sep 8 doi 1024875 ric21000206 online ahead printabstractautologous hematopoietic stem cell transplantation hsct given persons multiple sclerosis ms 20 years 3000 hscts done worldwide1 2 transplantrelated mortality ms managed hsct considered limiting factor decreased 22pmid34495949 doi1024875 ric21000206,0.0
skin care advice patients multiple sclerosis fingolimod treatment increased risk skin malignancyroom improvement ir j med sci 2021 sep 8 doi 101007 s1184502102768z online ahead printabstractfingolimod used treat relapsingremitting multiple sclerosis immunosuppressive effect predisposes skin malignancies summary product characteristics recommends persons receiving fingolimod educated regarding photoprotection vigilance skin lesions undergo dermatological evaluation initiation treatment 612 monthly thereafter incidence keratinocytic carcinomas longterm immunosuppression following solid organ transplantation declining trend coincided temporal changes immunosuppressive protocols introduction skin cancer prevention programmes suggesting risk developing malignancies may mitigated provision education patients amongst measures aim study assess health care professionals explaining skin advice documenting discussion prescribing fingolimod university hospital outpatient setting clinical records consecutive patients fingolimod reviewed data demographics documented provision advice skin protection provided advice collected fifty patients multiple sclerosis identified median age 405 years range 2563 fortytwo female 42 50 84 provision advice regarding skin protection documented 20 10 50 provided nurse specialists 14 7 50 doctors 10 5 50 4 2 50 risk developing skin cancers can reduced adoption simple preventative measures patients fingolimod increased risk developing cancers study demonstrates need improvement documentation advice around skin protectionpmid34495479 doi101007 s1184502102768z,0.0
role environmental factors multiple sclerosis expert rev neurother 2021 sep 8 doi 101080 1473717520211978843 online ahead printabstractintroduction environmental factors play significant role pathogenesis progression multiple sclerosis ms either acting alone interacting environmental genetic factors cumulative exposure external risk factors highly complex highly variable individualsareas covered authors narratively review current evidence role environmentspecific risk factors ms onset progression well effect geneenvironment interactions timing exposure ensure reviewed latest literature searched using ovid medline retrieving recently published systematic reviews metaanalyses recent studies previously included metaanalyses systematic reviewsexpert opinion good evidence suggesting impact environmental risk factors increasing risk developing ms tobacco smoking low vitamin d levels low sun exposure epstein barr virus ebv seropositivity history infectious mononucleosis may increase risk developing ms additionally evidence genesmoking geneebv smokingebv interactions affect risk ms onset however evidence role diverse environmental factors ms progression limited finally evidence tobacco smoking insufficient vitamin d levels sun exposure impacts ms phenotypes various markers disease activity including relapse disability progression mri findings clearly effect environmental factors ms disease course area requires significantly researchpmid34494502 doi101080 1473717520211978843,0.0
disease reactivation fingolimod discontinuation pregnant multiple sclerosis patients neurotherapeutics 2021 sep 7 doi 101007 s13311021011066 online ahead printabstractrecent studies estimated incidence 425 disease rebound withdrawal fingolimod fty reason specific data disease reactivation fty withdrawal due pregnancy limited aim study evaluate frequency predictors disease reactivation patients stopped fty pregnancy multicentre retrospective cohort study conducted four italian ms centres 20132019 planned unplanned pregnancies included annualized relapse rate arr calculated fty treatment fty treatment pregnancy year delivery total 27 patients mean age 29 years included arr 1 year fty treatment 13 patients exposed fty median 29 years arr 004 last year conception p 0001 compared arr fty treatment eleven patients became pregnant mean 88 days following fty discontinuation whereas 16 patients stopped fty pregnancy confirmation relapses observed 22 patients pregnancy 44 postpartum period arr increased pregnancy 049 p 0027 first year delivery 067 p 0001 compared last year pregnancy compared radiological assessment pregnancy patients showed new enlarging t2 lesions 63 vs 30 p 002 gadoliniumenhancing lesions 44 vs 0 p 00001 brain magnetic resonance imaging relapses pregnancy significant predictor postpartum relapses 19 95 ci 11131 one case spontaneous abortion cases abnormal foetal development observed despite adequate prolonged control disease activity women discontinue fty pregnancy risk disease reactivation patients relapsed pregnancy initiation highefficacy disease modifying drugs dmds soon delivery advisable prevent postpartum relapsespmid34494237 doi101007 s13311021011066,0.0
static dynamic pupillary characteristics multiple sclerosis eur j ophthalmol 2021 sep 811206721211044317 doi 101177 11206721211044317 online ahead printabstractpurpose examine static dynamic pupillary functions automated pupillography multiple sclerosis ms patients preserved visual acuitymethods fortyseven ms patients preserved visual acuity included study group 43 healthy volunteers control group visual evoked potential patients obtained routine ophthalmologic examination contrast sensitivity retinal nerve fiber layer rnfl thickness measured finally scotopic mesopic photopic pupillographies followed dynamic pupillography undertaken pupillary dilatation speed calculatedresults contrast sensitivity rnfl thickness ms group significantly lower control group p 005 ms control groups scotopic pupil diameters 548 103 528 078 mm mesopic pupil diameters 482 083 448 070 mm photopic pupil diameters 384 079 342 049 mm respectively p 0315 p 0044 p 0004 respectively dynamic pupillography pupil ms group dilated control group time sections examined except sixth second p 005 although mean pupillary dilation speed first second higher ms group p 0044 significant difference groups time intervals examined p 005 correlation pupillary parameters p100wave latency rnfl thickness contrast sensitivity p 005 conclusions static dynamic pupillary functions may affected ms patients preserved visual acuity although scotopic pupillary functions preserved mesopic photopic pupil functions weakenedpmid34493104 doi101177 11206721211044317,0.0
perspectives patient content analysis communication changes impact strategies facilitate communication multiple sclerosis int j speech lang pathol 2021 sep 7117 doi 101080 1754950720211973101 online ahead printabstractpurpose communication changes multiple sclerosis ms underexplored underrecognised persons ms pwms experts condition play valuable role informing clinicians researchers condition study aimed investigate perspectives pwms 1 msrelated communication changes 2 impact communication changes across key aspects persons life including work studies relationships general quality life 3 strategies used facilitate communication daily interactionsmethod twohundred sixty pwms recruited internationally completed online questionnaire content analysis used analyse openended questionnaire responsesresult onehundred ninetyseven 758 participants reported communication changes including language cognitive speech voice fluency changes participants described variety personal environmental factors influence communication negatively fatigue stress heat communication changes reported impact psychological wellbeing interpersonal relationships participation identity workforce career pathways tertiary studies around 40 participants reported using range overt covert strategies manage communication changes 112 n 22 197 participants reported communication changes accessed speechlanguage pathology slp servicesconclusion pwms can experience wide spectrum communication changes communication changes can profound farreaching impact psychological wellbeing societal participation engagement slp services limited compared reported prevalence communication changes need raise awareness role slp service provision pwms manage communication changes paper discusses provides suggestions slp services pwms communication changes timely need develop evidencebased interventions support pwms manage communication changes reduce impactpmid34493141 doi101080 1754950720211973101,0.0
functional role ascorbic acid central nervous system focus neurogenic synaptogenic processes nutr neurosci 2021 sep 8111 doi 101080 1028415x20211956848 online ahead printabstractascorbic acid watersoluble vitamin highly concentrated brain participates neuronal modulation regulation central nervous system cns homeostasis ascorbic acid emerged neuroprotective compound neurotoxicants neurodegenerative diseases including alzheimers disease multiple sclerosis amyotrophic lateral sclerosis moreover improves behavioral biochemical alterations psychiatric disorders including schizophrenia anxiety major depressive disorder bipolar disorder recent studies advanced knowledge mechanisms associated preventive therapeutic effects ascorbic acid showing linked improved neurogenesis synaptic plasticity review shows ascorbic acid potential regulate positively stem cell generation proliferation moreover improves neuronal differentiation precursors cells promotes adult hippocampal neurogenesis synaptogenic effects possibly linked protective therapeutic effects brainpmid34493165 doi101080 1028415x20211956848,1.0
cx3cl1 cx3cr1 signaling targets treatment neurodegenerative diseases pharmacol ther 2021 sep 4107989 doi 101016 jpharmthera2021107989 online ahead printabstractneuroinflammation initially thought consequence neurodegenerative disease pathology recently becoming clear plays significant role development progression disease thus neuroinflammation seen realistic valuable therapeutic target neurodegeneration neuroinflammation can modulated neuronglial signaling various soluble factors one critical modulator fractalkine cx3c motif chemokine ligand 1 cx3cl1 cx3cl1 produced neurons unique chemokine initially translated transmembrane protein can proteolytically processed generate soluble chemokine cx3cl1 shown signal sole receptor cx3cr1 located microglial cells within central nervous system cns although membrane bound soluble forms cx3cl1 appear interact cx3cr1 seem different signaling capabilities believed predominant function cx3cl1 within cns reduce proinflammatory response many studies shown neuroprotective effects however cases cx3cl1 appears promoting neurodegeneration review focusses presenting comprehensive overview complex nature cx3cl1 cx3cr1 signaling neurodegeneration may present therapeutic neurodegenerative diseases others role cx3cl1 cxcr1 reviewed context alzheimers disease ad parkinsons disease pd huntingtons disease hd ischemia retinopathies spinal cord neuropathic pain traumatic brain injury amyotrophic lateral sclerosis multiple sclerosis epilepsypmid34492237 doi101016 jpharmthera2021107989,1.0
accumulative risk clinical event highrisk radiologically isolated syndrome argentina data nationwide registry relevarem j neurol 2021 sep 7 doi 101007 s00415021107914 online ahead printabstractintroduction aimed analyze accumulative risk mri ob factors evolution ris ms subjects included argentinean ms registry nct03375177 methods ris subjects identified according ris diagnosis criteria subjects longitudinally followed clinical mri intervals 6 months time ris identification first clinical event estimated using kaplanmeier multivariable cox regression models created assess independent predictive value demographic characteristics well clinical ob mri data time first clinical event single increased risk factor evolution ris quantifiedresults total 88 ris subjects mean followup time 42 4 months included 39 443 23 261 new mri lesion clinical event respectively followup ob hr 59 95 ci 129101 p 0004 infratentorial lesions hr 37 95 ci 10975 spinal cord lesions hr 53 95 ci 1482 p 001 ris identification independent predictors associated subsequent clinical event accumulative risk showed two three factors ob infratentorial spinal cord lesions present hr 104 95 ci 4422 p 0001 three factors present hr 156 95 ci 5728 p 0001 relapseconclusion presence three factors significantly increased risk clinical event highrisk subjects probably managed different approach used individuals without highrisk factorspmid34491406 doi101007 s00415021107914,0.0
autoimmune diseases brain imaging clinical review neuroradiol j 2021 sep 719714009211042879 doi 101177 19714009211042879 online ahead printabstractthere extensive spectrum autoimmune entities can involve central nervous system expanded emergence new imaging modalities several clinicopathologic entities clinical presentation usually nonspecific imaging critical role workup diseases immunemediated diseases brain common daily practice radiologists except multiple sclerosis vague understanding differentiating based radiological findings review aim provide practical diagnostic approach based unique radiological findings disease hope diagnostic approach will help radiologists expand basic understanding discussed disease entities narrow differential diagnosis specific clinical scenarios understanding unique imaging features disorders along laboratory evaluation may enable clinicians decrease need tissue biopsypmid34490814 doi101177 19714009211042879,0.0
influence individual illness environmental factors place death among people neurodegenerative diseases retrospective observational comparative cohort study bmj support palliat care 2021 sep 6bmjspcare2021003105 doi 101136 bmjspcare2021003105 online ahead printabstractbackground longterm neurological conditions location death poorly understood seen marker quality dyingobjective examine individual illness environmental factors place death among people multiple sclerosis ms parkinsons disease pd isolation combination compare people without either conditionmethods retrospective observational comparative cohort study 582 people ms 579 people pd 95 controls uk multiple sclerosis parkinsons disease tissue bank subset people ms pd selected analysis individual clinical encounters 2 years death subset groups analysis impact advance care planning acp recognition dyingresults people ms died often 508 hospital pd 353 examining individual clinical encounters 2 years 4931 encounters identified increased contact services 12 months death f 1 58 6971 p00001 associated nonhospital deaths f 1 58 1001 p0321 presence acps recognition dying high among people ms pd associated nonhospital death acps likely prevent hospital deaths initiated general practitioners gps compared professional groups 26877 p00007 conclusions people ms pd acps contribute reducing dying hospital acps appear effective facilitated gps underlining importance primary care involvement delivering holistic care end lifepmid34489324 doi101136 bmjspcare2021003105,0.0
mir1423p regulates synaptopathydriven disease progression multiple sclerosis neuropathol appl neurobiol 2021 sep 7 doi 101111 nan12765 online ahead printabstractaim recently proposed mir1423p molecular player inflammatory synaptopathy new pathogenic hallmark multiple sclerosis ms mouse model experimental autoimmune encephalomyelitis eae leads neuronal loss independently demyelination mir1423p seems unique among potential biomarker candidates ms since inflammatory mirna playing dual role immune central nervous systems aimed verify impact mir1423p circulating cerebrospinal fluid csf ms patients clinical parameters neuronal excitability potential interaction disease modifying therapies dmts methods results cohort 151 ms patients found positive correlations csf mir1423p levels clinical progression il1 signalling well synaptic excitability measured transcranial magnetic stimulation furthermore therapy response patients low mir1423p dimethyl fumarate dmf established dmt superior patients high mir1423p levels accordingly eae clinical course heterozygous mir142 mice ameliorated peripheral dmf treatment greater impact relative wild type littermates addition central protective effect drug observed following intracerebroventricular ex vivo acute treatments eae wild type mice showing rescue mir1423pdependent glutamatergic alterations means electrophysiology molecular biochemical analysis suggest mir1423p molecular target dmfconclusion mir1423p novel potential negative prognostic csf marker ms promising tool identifying personalized therapiespmid34490928 doi101111 nan12765,1.0
psychotic symptoms prior concomitant diagnosis multiple sclerosis systematic review case reports case series int j psychiatry clin pract 2021 sep 617 doi 101080 1365150120211973506 online ahead printabstractobjective aimed examine clinical features psychotic symptoms preceding concomitant multiple sclerosis ms diagnosismethod 1st 10th january 2020 systematic review conducted electronic search different databases results limited english french german italian spanish language articlesresults identified 599 titles included 32 cases casereport case series one case report department added mean age first psychiatric symptoms 258 102 years mean age ms diagnosis 312 107 years mean delay ms diagnosis 27 3 years reported symptoms delusions 81 auditory hallucinations 59 visual hallucinations 50 upon ms diagnosis immunosuppressive therapy significantly effective psychotic symptoms antipsychotics 90 95ci 21537 p 0002 diffuse periventricular lesions found 956 cases mostly temporal frontal predominant lesions cases affected predominant temporal lesions 83 cases presented visual hallucinations p 005 conclusion poor response resistance antipsychotics treatment alert clinicians need consider differential diagnosis considering impact delay ms diagnosis research regarding subject warrantedkey pointsinsight occurrence psychotic symptoms multiple sclerosis ms mainly limited case reports case seriesdelay ms management initial psychotic symptoms ms diagnosis 273 3 years 08 12 years patients presenting first episode psychosisthe resistance poor response antipsychotics found cases 75 associated excellent improvement 95 psychiatric neurologic symptoms corticosteroidsprospective studies needed investigate spectrum psychosis mspmid34487465 doi101080 1365150120211973506,0.0
nonceliac gluten sensitivity underdiagnosed condition dermatology j eur acad dermatol venereol 2021 sep 6 doi 101111 jdv17642 online ahead printabstractnonceliac gluten sensitivity ncgs syndrome characterized intestinal bloating diarrhea extraintestinal symptoms headache fatigue others alleviated gluten free diet gfd subject meet criteria celiac disease cd wheat allergy 1 gluten main protein complex contained several cereals identified potential trigger syndrome prevalence syndromes far defined available data largely variablepmid34487592 doi101111 jdv17642,0.0
understanding covid19 risk patients immune mediated inflammatory diseases populationbased analysis sarscov2 testing arthritis care res hoboken 2021 sep 6 doi 101002 acr24781 online ahead printabstractobjective investigate incidence factors associated sarscov2 testing infection immune mediated inflammatory diseases imids versus matched nonimids comparators general populationmethods conducted populationbased matched cohort study among adult residents ontario canada january december 2020 created cohorts following imids rheumatoid arthritis ra psoriasis psoriatic arthritis ankylosing spondylitis systemic autoimmune rheumatic diseases multiple sclerosis ms iritis inflammatory bowel disease ibd polymyalgia rheumatica vasculitis patient matched five patients without imids based sociodemographic factors estimated incidence sarscov2 testing infection imids nonimids patients multivariable logistic regressions assessed odds sarscov2 infectionresults studied 493 499 patients imids 2 466 946 patients without imids patients imids likely least one sarscov2 test versus patients without imids 274 vs 227 proportion testing positive sarscov2 identical 09 groups overall imids patients 20 higher odds tested sarscov2 odds ratio 120 95 ci 119 121 odds sarscov2 infection varied across imids groups significantly elevated imid groups compared nonimids odds sarscov2 infection lower ibd ms marginally higher ra iritisconclusions patients across imids likely tested sarscov2 versus without imids risk sarscov2 infection varied across disease subgroupspmid34486829 doi101002 acr24781,0.0
symptomatic restorative therapies neuromyelitis optica spectrum disorders j neurol 2021 sep 5 doi 101007 s00415021107834 online ahead printabstractneuromyelitis optica spectrum disorders nmosd group autoimmune inflammatory conditions primarily target optic nerves spinal cord brainstem occasionally cerebrum nmosd characterized recurrent attacks visual motor sensory dysfunction often result severe neurological deficits recent years significant progress relapse treatment prevention residual disability per attack remains high although symptomatic restorative research limited nmosd therapeutic approaches can inferred published case series evidence multiple sclerosis literature review will discuss established emerging therapeutic options symptomatic treatment restoration function nmosd highlight nmosdspecific considerations identify potential areas future research review covers pharmacologic nonpharmacologic neuromodulatory approaches neuropathic pain tonic spasms muscle tone abnormalities sphincter dysfunction motor visual impairment fatigue sleep disorders neuropsychological symptoms addition briefly discuss remyelinating agents mesenchymal stem cell transplantation nmosdpmid34482456 doi101007 s00415021107834,1.0
pedal arterial calcification score associated risk major amputation chronic limbthreatening ischemia j vasc surg 2021 sep 2s07415214 21 019789 doi 101016 jjvs202107235 online ahead printabstractobjective medial arterial calcification mac score simple metric describes burden inframalleolar calcification based plain foot xray hypothesize higher mac score independently associated risk major amputation patients chronic limb threatening ischemia clti methods singleinstitution retrospective study 250 patients underwent infrainguinal revascularization clti 1 2011 7 2019 foot xrays available mac score calculation single blinded reviewer assigned mac scores 05 based twoview minimum plain foot radiographs 1 point calcification 2 cm dorsalis pedis plantar metatarsal arteries 1 cm hallux nonhallux digital arteriesresults mac score distribution 0 36 1 52 2 84 3 14 4 14 5 21 mac score trichotomized facilitate analysis clinical utility mild 01 moderate 24 severe 5 variables independently associated higher mac score male sex diabetes endstage renal disease esrd global limb anatomic staging system glass pedal score mac score associate society vascular surgery wound ischemia foot infection svs wifi grades overall wifi stage p058 median followup 759 days iqr 2641541 higher mac score significantly associated risk major amputation p00001 cox proportional hazards multiple regression model major amputation including trichotomized mac score diabetes esrd wifi stage 13 vs 4 mac score mac 5 p0001 hr 49 19131 mac 24 p001 hr 34 1388 wifi stage wifi 4 p003 hr 21 1139 significantly associated major amputation subsets patients advanced wifi stages 34 191 250 76 patients diabetes 185 250 74 mac stratified risk major amputation univariate multivariate analysesconclusions mac score simple practical tool strong independent predictor major amputation patients clti provides novel clinical data currently unmeasured validated clti staging system mac score promising standardized measure inframalleolar disease burden may used conjunction current wifi staging system help improve outcomes stratification determine optimal treatment strategies patients cltipmid34481900 doi101016 jjvs202107235,0.0
covid19 mrna vaccination leading cns inflammation case series j neurol 2021 sep 4 doi 101007 s00415021107807 online ahead printabstractthe availability vaccines severe acute respiratory syndrome coronavirus 2 sarscov2 provides hope towards mitigation coronavirus disease 2019 covid19 pandemic vaccine safety efficacy established individuals chronic autoimmune diseases multiple sclerosis ms anecdotal reports suggest vaccines may associated brain spinal cord peripheral nervous system cardiac inflammation based high morbidity unpredictable course covid19 need achieve herd immunity vaccination recommended patients ms report clinical mri features seven individuals received moderna n 3 pfizer n 4 sarscov2 mrna vaccines within one 21 days either first n 2 second n 5 vaccine dose patients developed neurologic symptoms mri findings consistent active cns demyelination optic nerve brain spinal cord symptoms included visual loss dysmetria gait instability paresthesias sphincter disturbance limb weakness age ranged 24 64 mean 391 years five woman 714 final diagnosis exacerbation known stable ms n 4 two receiving diseasemodifying therapy time vaccination new onset ms n 2 new onset neuromyelitis optica n 1 responded corticosteroid n 7 plasma exchange n 1 therapy five returning baseline two approaching baseline large prospective studies required investigate possible relationship covid19 vaccines acute cns demyelinationpmid34480607 doi101007 s00415021107807,1.0
global cerebrospinal fluid zeroreference regularization brain quantitative susceptibility mapping j neuroimaging 2021 sep 4 doi 101111 jon12923 online ahead printabstractbackground purpose objective ofthis study demonstrate global cerebrospinal fluid csf method consistent automated zero referencing brain quantitative susceptibility mapping qsm methods whole brain csf mask automatically segmented thresholding gradient echo transverse relaxation r 2 map regularization employed enforce uniform susceptibility distribution within csf volume fieldtosusceptibility inversion global csf regularization method compared prior ventricular csf regularization reconstruction methods compared repeatability study 12 healthy subjects using ttest susceptibility measurements patient studies 17 multiple sclerosis ms 10 parkinsons disease pd patients using wilcoxon ranksum test radiological scoresresults scanrescan experiments global csf regularization provided consistent csf volume well higher repeatability qsm measurements ventricular csf regularization smaller bias 27 parts per billion ppb versus 013 ppb ttest p005 narrower 95 limits agreement 725 699 ppb versus 1660 1119 ppb ftest p005 pd ms patients global csf regularization reduced smoothly varying shadow artifacts significantly improved qsm quality score p0001 conclusions proposed whole brain csf method qsm zero referencing improves repeatability image quality brain qsm compared ventricular csf methodpmid34480496 doi101111 jon12923,0.0
potential costeffectiveness cellbased bioelectronic implantable device delivering interferonbeta1a therapy versus injectable interferonbeta1a treatment relapsingremitting multiple sclerosis pharmacoeconomics 2021 sep 4 doi 101007 s4027302101081y online ahead printabstractbackground current firstline diseasemodifying therapies dmt multiple sclerosis ms patients injectable oral treatments optogenerapy consortium developing novel bioelectronic cellbased implant controlled release betainterferon ifn1a protein body current study estimated potential cost effectiveness optogenerapy implant hereafter optoferon compared injectable ifn1a avonex methods markov model simulating costs effects optoferon compared injectable 30 mg ifn1a 9year time horizon dutch societal perspective costs reported 2019 euros discounted 4 annual rate health effects discounted 15 annual rate cohort consisted 35yearold relapsingremitting ms patients mild disability device implanted daycare setting replaced every 3 years basecase analysis assumed equal input parameters optoferon avonex regarding disability progression health effects adverse event probabilities acquisition costs assumed reduced annual relapse rates withdrawal rates optoferon compared avonex sensitivity scenario value information headroom analysis performedresults optoferon dominant strategy cost reductions 26 966 health gains 045 qualityadjusted lifeyears gained main driver cost differences acquisition costs optoferon 25 times less costs avonex incremental costeffectiveness ratio sensitive variations annual acquisition costs avonex annual withdrawal rate avonex optoferon disability progression avonexconclusion innovative technology optoferon implant may costeffective therapy patients ms novel implantable mode therapeutic protein administration potential become new mode treatment administration ms patients disease areas however trials needed establish safety effectivenesspmid34480325 doi101007 s4027302101081y,0.0
engineered exosomes promising drug delivery strategy brain disease curr med chem 2021 sep 2 doi 102174 0929867328666210902142015 online ahead printabstractexosomes heterogeneous group nanosized natural membrane vesicles released various cells exist body fluids different previous understanding function exosomes garbage bins exosomes act carriers many kinds bioactive molecules eg proteins lipids nucleic acids play important role cellcell communication growing evidence recent years suggested exosomes also play roles pathogenesis diagnosis treatment modalities brain diseases including ischemic stroke alzheimers disease parkinsons disease multiple sclerosis brain cancers exosomes therapeutic drug carriers brain drug delivery received extensive attention well exosomes can overcome bloodbrain barrier bbb however low targeting ability sizedependent cellular uptake native exosomes profoundly affect delivery performance exosomes recent studies indicated engineered exosomes can increase drug uptake efficiency subsequent drug efficacy present paper will briefly introduce engineering methods applications engineered exosomes treatment brain diseases focus discussing advantages challenges exosomebased drug delivery platforms enrich boost development exosomes promising drug delivery strategy brain diseasespmid34477508 doi102174 0929867328666210902142015,0.0
obesity status obesityassociated gut dysbiosis effects hypothalamic structural covariance int j obes lond 2021 sep 1 doi 101038 s41366021009539 online ahead printabstractbackground functional connectivity alterations lateral medial hypothalamic networks associated development maintenance obesity possible impact structural properties networks remains largely unexplored also obesityrelated gut dysbiosis may delineate specific hypothalamic alterations within obese conditions aim assess effects obesity obesity gutdysbiosis structural covariance differences hypothalamic networks executive functioning depressive symptomsmethods medial mh lateral lh hypothalamic structural covariance alterations identified 57 subjects obesity compared 47 subjects without obesity gut dysbiosis subjects obesity defined presence high n 28 low n 29 values bmiassociated microbial signature posthoc comparisons groups used proxy explore role obesityrelated gut dysbiosis hypothalamic measurements executive function depressive symptomsresults structural covariance alterations mh striatum lateral prefrontal cingulate insula temporal cortices congruent previously functional connectivity disruptions obesity conditions mh structural covariance decreases encompassed postcentral parietal cortices subjects obesity gutdysbiosis increases subcortical nuclei involved coding foodrelated hedonic information subjects obesity without gutdysbiosis alterations structural covariance lh subjects obesity gutdysbiosis encompassed increases frontolimbic networks decreases lateral orbitofrontal cortex subjects obesity without gutdysbiosis subjects obesity gut dysbiosis showed higher executive dysfunction depressive symptomsconclusions obesityrelated gut dysbiosis linked specific structural covariance alterations hypothalamic networks relevant integration somaticvisceral information emotion regulationpmid34471225 doi101038 s41366021009539,0.0
deep attention graphical neural network multiple sclerosis lesion segmentation mr imaging sequences ieee j biomed health inform 2021 sep 1 pp doi 101109 jbhi20213109119 online ahead printabstractthe segmentation multiple sclerosis ms lesions mr imaging sequences remains challenging task due characteristics variant shapes scattered distributions unknown numbers lesions however current automated ms segmentation methods deep learning models face challenges 1 capturing multiple scattered lesions multiple regions 2 delineating global contour variant lesions address challenges paper propose novel attention graphdriven network dagnet incorporates 1 spatial correlations embracing lesions distant regions 2 global context better representing lesions variant features unified architecture firstly novel local attention coherence mechanism designed construct dynamic expansible graphs spatial correlations pixels proximities secondly proposed spatialchannel attention module enhances features optimize global contour delineation aggregating relevant features moreover dynamic graphs learning process dagnet interpretable turns support reliability segmentation results extensive experiments conducted public isbi2015 dataset inhouse dataset comparison stateoftheart methods based geometrical clinical metrics experimental results validate effectiveness proposed dagnet segmenting variant scatted lesions multiple regionspmid34469321 doi101109 jbhi20213109119,0.0
cholesterol dyshomeostasis amyotrophic lateral sclerosis cause consequence epiphenomenon febs j 2021 sep 1 doi 101111 febs16175 online ahead printabstractamyotrophic lateral sclerosis als common adultonset motor neuron disease characterized selective degeneration motor neurons leading paralysis eventual death multiple pathogenic mechanisms including systemic dysmetabolism proposed contribute als among dyslipidemia ie abnormal level cholesterol lipids circulation central nervous system cns reported als patients without consensus cholesterol constituent cellular membranes precursor steroid hormones oxysterols bile acids consequently optimal cholesterol levels essential health due bloodbrain barrier bbb cholesterol move cns rest body cholesterol metabolism cns proposed operate autonomously despite importance remains elusive cholesterol dyshomeostasis may contribute als review aim describe current state cholesterol metabolism research als identify unresolved issues provide potential directionspmid34469619 doi101111 febs16175,0.0
nonmemory composite embedded performance validity formulas patients multiple sclerosis arch clin neuropsychol 2021 aug 31acab066 doi 101093 arclin acab066 online ahead printabstractobjective research regarding performance validity tests pvts patients multiple sclerosis ms scant recommended batteries neuropsychological evaluations population lacking suggestions include pvts moreover limited work examined embedded pvts population previous investigations indicated nonmemorybased embedded pvts provide clinical utility populations study sought determine logistic regressionderived pvt formula can identified selected nonmemory variables sample patients msmethod total 184 patients m age 4845 766 female ms referred neuropsychological assessment large midwestern academic medical center patients placed credible n 146 noncredible n 38 groups according performance standalone pvt missing data imputed hotdeckresults classification statistics variety embedded pvts examined none appearing psychometrically appropriate isolation areas curve aucs 4864 four exponentiated equations created via logistic regression six five three predictor equations yielded acceptable discriminability auc 7174 modest sensitivity 3439 maintaining good specificity 90 two predictor equation appeared unacceptable auc 67 conclusions results suggest multivariate combinations embedded pvts may provide clinical utility minimizing test burden determining performance validity patients ms nonetheless authors recommend routine inclusion several pvts utilization comprehensive clinical judgment maximize signal detection noncredible performance avoid incorrect conclusions clinical implications limitations avenues future research discussedpmid34467368 doi101093 arclin acab066,0.0
content effects trunk rehabilitation trunk upper limb performance people multiple sclerosis systematic review eur j phys rehabil med 2021 sep 1 doi 1023736 s1973908721066892 online ahead printabstractintroduction persons multiple sclerosis pwms impaired trunk reduced postural control negatively impacts activities daily living evidence growing consider positive effects trunk training fall incidence balance problems effects trunk upper limb performance unknown systematic review provides overview trunk training programs effects ms specifically focusing content training modalities effects trunk upper limb performanceevidence acquisition two electronic databases used pubmed web science wos intervention studies without control group published english investigating effects active trunk training trunk upper limb performance pwms includedevidence synthesis sixteen studies met criteria investigating different rehabilitation modalities included interventions review varied generic postural interventions pilates n8 ai chi n1 focus abdominal muscle activation breathing neutral position lower extremity movements specifically developed trunk training programs like groupcoredist sit coduse n 6 bobath based trunk training n1 detected main focus trunk strengthening dynamic movements overall improvement trunk performance reported several tests trunk strength stability coordination majority programs integrated upper limb half used upper limb outcome measures evaluate effect overall significant improvements found upper limbconclusions systematic review showed different types trunk training programs can improve trunk upper limb function pwms findings review suggest focus trunk training achieve effects upper limb reasonable future research needed explore relations effect sizespmid34468108 doi1023736 s1973908721066892,0.0
nuclearimport receptors counter deleterious phase transitions neurodegenerative disease j mol biol 2021 aug 28167220 doi 101016 jjmb2021167220 online ahead printabstractnuclearimport receptors nirs engage nuclearlocalization signals nlss polypeptides cytoplasm transport cargo across sizeselective barrier nuclearpore complex nucleoplasm beyond canonical role nuclear transport nirs operate cytoplasm chaperone disaggregate nlsbearing clients indeed nirs can inhibit reverse functional deleterious phase transitions cargo including several prominent neurodegenerative diseaselinked rnabinding proteins rbps prionlike domains prlds tdp43 fus ewsr1 taf15 hnrnpa1 hnrnpa2 importantly elevated nir expression can mitigate degenerative phenotypes connected aberrant cytoplasmic aggregation rbps prlds review recent discoveries nirs can also antagonize aberrant interactions toxicity argininerich dipeptiderepeat proteins associated amyotrophic lateral sclerosis als frontotemporal dementia ftd caused g4c2 hexanucleotide repeat expansions first intron c9orf72 also highlight recent findings multiple nir family members can prevent reverse liquidliquid phase separation specific clients bearing rgg motifs nlsindependent manner finally discuss strategies enhance nir activity expression therapeutic utility several neurodegenerative disorders including als ftd multisystem proteinopathy limbicpredominant agerelated tdp43 encephalopathy tauopathies related diseasespmid34464655 doi101016 jjmb2021167220,0.0
realworld data regarding longterm administration natalizumab neurology department along literature review cns neurol disord drug targets 2021 aug 26 doi 102174 1871527320666210827113733 online ahead printabstractbackground natalizumab humanized monoclonal antibody high efficacy acceptable safety profile used treatment patients multiple sclerosis ms objectives aim report data regarding longterm administration natalizumab patients relapsingremitting multiple sclerosis rrms clinicmethods retrospective observational study performed including rrms patients underwent treatment 24 natalizumab infusions analyzed edss values relapse rate rate type adverse events related natalizumab administrationresults 51 subjects included predominance women 6274 average age 4043149 years mean disease duration 98607 years mean number natalizumab infusions 4558274 increased number patients 8039 relapsefree observed mild reduction mean edss value following natalizumab initiation patients treated disease modifying therapies anteriorly among encountered adverse events registered increased liver transaminases 1372 local infections 784 dysmenorrhea one patient rate severe adverse events 392 registered cases progressive multifocal leukoencephalopathy pml conclusions natalizumab proves effective adequate safety profile can administered good tolerability rather extended period time provided patients closely monitoredpmid34455973 doi102174 1871527320666210827113733,0.0
global intertuberal epileptic networks tuberous sclerosis based stereoelectroencephalographic seeg findings quantitative eeg analysis pediatric subjects surgical implications childs nerv syst 2021 aug 29 doi 101007 s00381021053421 online ahead printabstractobjective recent evidence favors network concept tuberous sclerosis tsc seizure generation propagation related changes global regional connectivity multiple anatomically distant tubers direct exploration network dynamics tsc made possible intracranial sampling stereoelectroencephalography seeg objective study define epileptic networks tsc using quantitative analysis seeg recordings also discuss impact definition epileptic networks surgical decisionmakingmethods intracranial seeg recordings obtained four pediatric patients presented medically refractory epilepsy secondary tsc subjected quantitative signal analysis methods cortical connectivity quantified calculating pairwise coherence contacts constructing association matrix global coherence defined ratio largest eigenvalue sum eigenvalues calculated frequency band delta theta alpha beta gamma spatial distribution connectivity identified plotting leading principal component product largest eigenvalue corresponding eigenvector results four pediatric subjects tsc underwent invasive intracranial monitoring seeg comprising 31 depth electrodes 250 contacts localization epileptogenic focus guidance subsequent surgical intervention quantitative connectivity analysis revealed change global coherence ictal period beta low gamma 1430 hz high gamma 3180 hz bands results corroborate findings existing literature implicate higher frequencies driver synchrony desynchronyconclusions coordinated highfrequency activity beta low gamma high gamma bands among spatially distant seeg define ictal period tsc timedependent change global coherence demonstrates evidence intratuberal intertuberal connectivity tsc observation surgical implications suggests targeting multiple tubers higher chance seizure control higher chance disrupting epileptic network use laser interstitial thermal therapy litt allowed us target multiple disparately located tubers minimally invasive manner good seizure control outcomespmid34455445 doi101007 s00381021053421,0.0
genes associated grey matter volume reduction multiple sclerosis j neurol 2021 aug 29 doi 101007 s00415021107772 online ahead printabstractthere extensive grey matter volume gmv reduction multiple sclerosis ms may account cognitive impairment disabling disorder although genomewide association studies gwass identified hundreds genes associated ms know little genes associated gmv reduction cognitive decline ms present study aimed uncover genes associated gmv reduction ms performing crosssample 1473 brain tissue samples partial least squares regression gene expression 6 postmortem brains casecontrol gmv difference ms metaanalysis 1391 patients 1189 controls discovery phase intergroup comparison 69 patients 70 controls replication phase identified 623 genes whose brain spatial expression profiles significantly associated gmv reduction ms genes showed significant enrichment msrelated genes identified gwas functionally associated ion channel synaptic transmission axon neuron projection showed significant cell typespecific expression neurons cell types importantly identified genes showed significant enrichment genes downregulated rather upregulated expression ms spatial distribution patterns expression identified genes showed significant correlations brain activation patterns memory language tasks findings indicate grey matter atrophy ms may resulted joint effects multiple genes associated disorder especially genes downregulated expression mspmid34455470 doi101007 s00415021107772,0.0
lessons s1p receptor targeting multiple sclerosis pharmacol ther 2021 aug 24107971 doi 101016 jpharmthera2021107971 online ahead printabstractsphingosine 1phosphate s1p potent bioactive sphingolipid binding specific g proteincoupled receptors expressed several organs relevance s1ps1p receptor axis pathophysiology immune nervous systems encouraged development s1p receptor modulators treatment neurological autoimmune inflammatory disorders currently four s1p receptor modulators approved drugs multiple sclerosis ms inflammatory disorder central nervous system main pharmacologic effect treatments induce lymphopenia due loss responsiveness s1p gradients guiding lymphocyte egress lymphoid organs bloodstream recent data point immunological effects s1p modulators beyond inhibition lymphocyte trafficking drugs may cross bloodbrain barrier directly target cns resident cells expressing s1p receptors review role s1p signalling neuroimmunology light evidences generated study mechanism action s1p receptor modulators ms integrate information findings derived neuroinflammatory animal models vitro observations insights can direct application therapeutic approaches targeting s1p receptors disease areaspmid34450231 doi101016 jpharmthera2021107971,0.0
mth1 target alleviate t cell driven diseases selective suppression activated t cells cell death differ 2021 aug 27 doi 101038 s41418021008544 online ahead printabstractt celldriven diseases account considerable morbidity disability globally urgent need new targeted therapies cancer cells activated t cells altered redox balance upregulate dna repair protein mth1 sanitizes oxidized nucleotide pool avoid dna damage cell death herein suggest upregulation mth1 activated t cells correlates redox status occurs ros levels increase challenging established conception mth1 increasing direct response increased ros status also propose heterogeneity mth1 levels among activated t cells smaller subset activated t cells upregulate mth1 despite activation proliferation study suggests vast majority activated t cells high mth1 levels sensitive mth1 inhibitor th1579 karonudib via induction dna damage cell cycle arrest th1579 drives surviving cells mth1low phenotype altered redox status th1579 affect resting t cells opposed established immunosuppressor azathioprine sensitivity among major immune cell types regarding function can observed finally demonstrate therapeutic effect murine model experimental autoimmune encephalomyelitis conclusion show proof concept existence mth1high mth1low activated t cells mth1 inhibition th1579 selectively suppresses proinflammatory activated t cells thus mth1 inhibition th1579 may serve novel treatment option autoreactive t cells autoimmune diseases multiple sclerosispmid34453118 doi101038 s41418021008544,0.0
dysregulated translational factors epigenetic regulations orchestrate b cells contributing autoimmune diseases int rev immunol 2021 aug 27125 doi 101080 0883018520211964498 online ahead printabstractb cells play crucial role antigen presentation antibody production pro antiinflammatory cytokine secretion adaptive immunity several translational factors including transcription factors cytokines participate regulation b cell development cooperation epigenetic regulations autoimmune diseases generally characterized autoreactive b cells highlevel pathogenic autoantibodies success b cell depletion therapy mouse model clinical trials proven role b cells pathogenesis autoimmune diseases failure b cell tolerance immune checkpoints results accumulated autoreactive nave b bn cells aberrant b cell receptor signaling dysregulated b cell response contributing selfantibodymediated autoimmune reaction dysregulation translational factors epigenetic alterations b cells demonstrated correlate aberrant b cell compartment autoimmune diseases systemic lupus erythematosus rheumatoid arthritis primary sjgrens syndrome multiple sclerosis diabetes mellitus pemphigus review intended summarize interaction translational factors epigenetic regulations involved development differentiation b cells mechanism dysregulation pathogenesis autoimmune diseasespmid34445929 doi101080 0883018520211964498,0.0
fatigue limiting factor vaginal birth patients multiple sclerosis neuro endocrinol lett 2021 aug 26 42 4 222228 online ahead printabstractobjectives multiple sclerosis ms chronic autoimmune neurodegenerative disease study evaluated pregnancyrelated issues patients ms one perinatological centrematerial methods singlecentre retrospective study perinatal period patients ms admitted dpt gynaecology obstetrics jessenius faculty medicine comenius university university hospital martin slovak republic european union january 1 2015 december 1 2020 performed selected parameters personal obstetric neurological histories analysedresults cohort 15 patients 32553 years relapsingremitting form ms gave birth 16 children mean length ms time delivery 936 years severity expanded disability status scale score 2015 caesarean section cs indicated 14 deliveries 875 elective cs 10 patients common indication elective cs combination significant chronic fatigue syndrome neurological deficit paresis conclusions basis management pregnancy childbirth postpartum period women ms planned pregnancy based close cooperation among patients gynaecologists neurologists vaginal delivery primarily contraindicated indications cs considered individually one way minimise indications cs accurate diagnosis personalised treatment fatigue pregnant women ms presumably obstetricians neurologists prefer vaginal delivery first choice patients fatigue syndromepmid34436842,0.0
preliminary efficacy quot sitless msquot intervention changing sedentary behaviour symptoms physical performance multiple sclerosis disabil rehabil 2021 aug 2518 doi 101080 0963828820211966520 online ahead printabstractpurpose people multiple sclerosis ms sit ie sedentary peers examined preliminary efficacy internetbased intervention focuses sitting less moving changing sedentary behaviour outcomes symptoms qol physical performance adults msmethods persons mildtomoderate disability ms took part 15week prepost trial outcomes including sedentary behaviour representative symptoms eg fatigue pain qol physical performance measures eg walking speed measured three time points prepost intervention followup unstructured linear mixedeffects model used determine change time per outcomeresults fortyone persons ms participated age 50 103 years significant reductions total sedentary time d 034 number long 30 min bouts sedentary time d 039 postintervention symptoms physical performance measures significantly improved following intervention effects sizes greatest fatigue d 061 depression d 079 changes maintained 7week followup except sedentary behaviour outcomes sleep quality cognition changeconclusions study provides preliminary support efficacy intervention focused sitting less moving improving symptoms adults msimplications rehabilitationthis research provides preliminary evidence intervention aimed reducing sedentary behaviour increasing light intensity activity throughout day can impactfatigue depression anxiety symptoms frequently encountered people ms showed greatest improvement following interventionweekly coaching sessions including discussions results activity monitoring provided motivation participantstrial registration sitless ms feasibility study registered clinicaltrialsgov trial registration number nct03136744 date registration 2 may 2017 find https clinicaltrialsgov ct2 show nct03136744pmid34433359 doi101080 0963828820211966520,1.0
histamine multiple sclerosis alliance pleiotropic actions functional validation curr top behav neurosci 2021 aug 26 doi 101007 7854_2021_240 online ahead printabstractmultiple sclerosis ms disease resilient inflammatory component caused accumulation cns inflammatory infiltrates macrophage microglia contributing severe demyelination neurodegeneration causes still part unclear key pathogenic mechanisms direct loss myelinproducing cells impairment caused immune system proposed etiology includes genetic environmental factors triggered viral infections although several diagnostic methods new treatments development curative palliative care relapsingremitting progressive forms ms recent times boost awareness role histamine signaling physiological pathological functions nervous system particularly ms evidence raising histamine might directly implicated disease acting different cellular molecular levels instance constitutively active histamine regulates differentiation oligodendrocyte precursors thus playing central role remyelination process histamine reduces ability myelinautoreactive t cells adhere inflamed brain vessels crucial step development ms histamine levels found increased cerebrospinal fluid ms patients aim present work present proofs alliance histamine ms introduce recent innovative histamine paradigms therapy will report longstanding molecule previously recognized immunomodulatory neuroprotective functions histamine might still provide renewed farreaching role mspmid34432258 doi101007 7854_2021_240,1.0
role d2like dopaminergic receptor dopaminemediated modulation th17cells multiple sclerosis curr neuropharmacol 2021 aug 22 doi 102174 1570159x19666210823103859 online ahead printabstractdopamine direct mediator neuroimmune interaction may play significant role multiple sclerosis ms pathogenesis modulating immune cell activity cytokine production studied effects dopamine th17cells function 34 patients relapsingremitting ms 23 healthy subjects production interleukin17 il17 interferon ifn granulocytecolony stimulating factor gmcsf il21 cd4+ tcells well dopamine comparable groups dopamine suppressed il17 ifn gmcsf il21 production stimulated d4+ tcells groups blockade d1like dopaminergic receptor specific antagonist sch23390 affect dopaminemediated cytokine suppression contrast blockade d2like dopaminergic receptor sulpiride decreased dopamines inhibitory effect il17 secretion groups gmcsf il21 production ms patients blockade d1like dopaminergic receptor directly inhibited il17 ifn gmcsf groups il21 production healthy subjects blockade d2like dopaminergic receptor effect cytokine secretion finally activation d2like dopaminergic receptor specific agonist quinpirole decreased il17 ifn gmcsf production groups data suggest inhibitory role dopamine th17cells ms mediated activation d2like dopaminergic receptorpmid34429055 doi102174 1570159x19666210823103859,0.0
asymmetric alterations white matter integrity patients insomnia disorder brain imaging behav 2021 aug 24 doi 101007 s1168202100512w online ahead printabstractdespite adverse consequences insomnia disorder individuals society underlying neurobiological processes poorly understood purpose understand alterations white matter tracts patients insomnia association sleep variables also determine diffusion tensor imaging measures useful disease marker twentysix patients insomnia 26 agematched healthy volunteers underwent diffusion tensor imaging employed automated probabilistic tractography analysis approach using tracts constrained underlying anatomy tracula quantify diffusion measures major white matter tracts found significantly increased fractional anisotropy right cingulumangular bundle uncinate fasciculus patients group compared controls moreover mean diffusivity radial diffusivity reduced right cingulumangular bundle patients group comparison controls also found significantly increased fractional anisotropy along bilateral cingulumangular bundle right uncinate fasciculus patients also mean radial diffusivity reduced along right cingulumangular bundle patients group compared controls significant positive correlation fractional anisotropy epworth sleepiness scale scores moreover negative correlations mean radial axial diffusivity total sleep time sleep efficiency also positive correlations mean radial axial diffusivity duration disease pittsburgh sleep quality index scores study showed importance examining wholetract waypoint white matter integrity insomnia disorder found asymmetric widespread white matter integrity changes patients insomniapmid34427878 doi101007 s1168202100512w,0.0
bingneel syndrome hidden multiple sclerosis challenging overlay diseases acta neurol belg 2021 aug 23 doi 101007 s13760021017770 online ahead printno abstractpmid34424495 doi101007 s13760021017770,0.0
regional cerebellar volume loss predicts future disability multiple sclerosis patients cerebellum 2021 aug 21 doi 101007 s12311021013120 online ahead printabstractcerebellar symptoms multiple sclerosis ms well described however exact contribution cerebellar damage ms disability fully explored longerterm observational periods necessary better understand dynamics pathological changes within cerebellum clinical consequences cerebellar lobe single lobule volumes automatically segmented 664 3dt1weighted mprage scans acquired single 15 t scanner 163 ms patients 111 women mean age 471 years 125 relapsingremitting rr 38 secondary progressive sp ms median edss 30 imaged annually 4 years clinical scores edss 9hpt 25fwt pasat sdmt determined per patient per year maximum clinical followup 11 years linear mixedeffect models applied assess association cerebellar volumes clinical scores whether cerebellar atrophy measures may predict future disability progression spms patients exhibited faster posterior superior lobe volume loss time compared rrms related increase edss time rrms cerebellar volumes significant predictors motor scores eg average edss t25fwt 9hpt sdmt atrophy motorassociated lobules ivvi + viii significant predictor future deterioration 9hpt nondominant hand spms atrophy rate posterior superior lobe vi + crus significant predictor future pasat performance deterioration regional cerebellar volume reduction associated motor cognitive disability ms may serve predictor future disease progression especially dexterity impaired processing speedpmid34417983 doi101007 s12311021013120,0.0
incidence optic neuritis associated risk multiple sclerosis service members us armed forces mil med 2021 aug 21usab352 doi 101093 milmed usab352 online ahead printabstractintroduction optic neuritis acute inflammation optic nerve resulting eye pain temporary vision loss one leading causes visionrelated hospital bed days us military may harbinger multiple sclerosis ms developed case identification algorithm estimate incidence rates conversion rate ms based retrospective assessment medical records service members sms us armed forcematerials methods electronic medical records emrs 2006 2018 defense medical surveillance system screened using case identification algorithms ms diagnosis incidences rates calculated rates conversion ms modeled using kaplanmeier survival analysisresults overall incidence rate 81 per 100 000 2006 2018 females rate 169 per 100 000 three times higher males 68 subsequent diagnoses ms made within 1 year diagnosis overall 5year risk progression ms 15 1116 95 ci risk conversion ms females significantly higher malesconclusions developed efficient tool explore emr database estimate burden us military ms conversion based dynamic cohort estimated conversion rates ms feeds inform retention fitnessforduty policy smspmid34417807 doi101093 milmed usab352,0.0
muscle architecture relationship lower extremity muscle strength multiple sclerosis acta neurol belg 2021 aug 20 doi 101007 s13760021017681 online ahead printabstractthis study planned determine muscle architecture pennation angle muscle fiber length muscle thickness relationship lower extremity muscle strength patients multiple sclerosis pwms muscle architecture pennation angle muscle fiber length muscle thickness lower extremity muscle strength assessed 33 pwms 13 relapsingremitting ms rrms 5 primary progressive ms ppms 5 secondary progressive ms spms 11 matched healthy controls hc muscle architecture features assessed ultrasonography muscle strength assessed digital handheld dynamometer rectus femoris muscle thickness pennation angle gastrocnemius muscle thickness tibialis anterior pennation angle significantly lower pwms compared hc p 005 strength hip flexors hip extensors knee extensors foot plantar foot dorsi flexors lower pwms ppms group muscle strength hip flexors lower rrms spms groups muscle strength foot dorsi flexors lower rrms p 005 pwms positive correlations found knee flexor strength biceps femoris pennation angle also knee extensor strength rectus femoris fiber length muscle thickness correlated positively p 005 according results muscle architecture affected ms determination architectural changes lower extremity muscles may guide arrangement optimal strength exercises functional rehabilitation programsclinicaltrials nct03766698pmid34417688 doi101007 s13760021017681,0.0
proposal study promyelinating proteins ms autoimmun rev 2021 aug 17102924 doi 101016 jautrev2021102924 online ahead printabstractmultiple sclerosis ms inflammatory degenerative disease cns unmet need ms repair ie promoting endogenous regeneration remyelination demyelinating inflammatory injury remyelination critical neuronal preservation prevention clinical progression good deal evidence histological repair remyelination ms patients repair driven several prominent endogenous promyelinating proteinsincluding neural cellular adhesion molecule ncam brain derived neurotrophic factor bdnf among others follow changes acute remyelination vivo ms subjects non conventional mri techniques necessary quantitative susceptibility mapping qsm detects release fe dying oligodendroglial cells myelin water imaging mwi detects water captured within newly formed myelin best time monitor changes promyelinating proteins link changes imaging evolution immediately acute inflammatory response ms lesions gadolinium enhancement gd+ intense period remyelination can monitor ms subjects new gd + lesions periodic imaging along sampling blood csf determine myelin formation linked increases promyelinating proteins lead potential therapeutic manipulation directly administered proteins promote cns remyelination animal models early clinical trialspmid34416371 doi101016 jautrev2021102924,1.0
extracellular vesicles stem cells role mirnas neurodegeneration curr neuropharmacol 2021 aug 17 doi 102174 1570159x19666210817150141 online ahead printabstractthere different modalities intercellular communication governed cellular homeostasis review will explore one forms communication called extracellular vesicles evs vesicles released cells body heterogeneous nature primary function evs share information cargo consisting proteins lipids nucleic acids mrna mirna dsdna etc cells direct consequence microenvironment will focus role evs mesenchymal stem cells mscs nervous system participate intercellular communication maintain physiological function provide neuroprotection however deregulation communication system play role several neurodegenerative diseases alzheimers disease parkinsons disease amyotrophic lateral sclerosis multiple sclerosis prion disease huntingtons disease release evs cell provides crucial information happening inside cell thus used diagnostics therapy will discuss explore new avenues clinical applications using engineered mscevs potential therapeutic benefit treating neurodegenerative diseasespmid34414870 doi102174 1570159x19666210817150141,0.0
genetic epigenetic control clock genes multiple sclerosis j genet genomics 2021 aug 16s16738527 21 002587 doi 101016 jjgg202107016 online ahead printno abstractpmid34411713 doi101016 jjgg202107016,0.0
hemostatic factors pathogenesis neuroinflammation multiple sclerosis mult scler 2021 aug 1913524585211039111 doi 101177 13524585211039111 online ahead printabstractbackground growing body evidence shed light role hemostatic pathway components pathogenesis multiple sclerosis ms particularly enhancing sustaining neuroinflammationobjective review clinical experimental neuroimaging evidence supporting role different components hemostatic pathway pathogenesis neuroinflammation ms discuss translational potential disease biomarkers therapeutic targetsmethods literature search relevant articles 1956 2020 conducted pubmed scopusresults hemostasis components appear involved different key events neuroinflammation ms including mononuclear cell diapedesis microglia activation neuronal damageconclusion findings interplay hemostatic thrombotic molecular pathways pathogenesis neuroinflammation ms open new opportunities developing novel biomarkers disease monitoring prognosis well novel therapeutic targetspmid34410198 doi101177 13524585211039111,0.0
relationship fall status cognition cerebellar lobule volume patients multiple sclerosis appl neuropsychol adult 2021 aug 19111 doi 101080 2327909520211962881 online ahead printabstractin prospective case control study relationship detailed cerebellar volumetric data cognition patients multiple sclerosis considering falling status using 3 d mri network analysis evaluated participants consist 106 adults relapsingremitting multiple sclerosis scores montreal cognitive assessment test symbol digit modality test ninehole peg test berg balance scale test timed go test timed 25foot walk test worse faller group non faller group p 005 tests significant difference terms cerebellar lobule volumes groups using artificial intelligence ai based network analysis brought new perspective interpreting relationship cerebellum cognition gait balance overall data study suggest possible relationship cerebellar volume changes cognitive dysfunction connectivity analysis patients multiple sclerosis studies needed examine issue using connectivity analysispmid34410894 doi101080 2327909520211962881,0.0
epidemiology multiple sclerosis iraq retrospective review 4355 cases literature review neurol res 2021 aug 19110 doi 101080 0161641220211952511 online ahead printabstractobjectives multiple sclerosis ms progressive demyelinating degenerative disease cns highly variable geographically objectives establish comprehensive nationwide ms epidemiological data compare similar studies conducted regional international communities best knowledge first nationwide comprehensive epidemiological study conducted iraqmethods retrospective study including 4355 ms cases 10 officially authorized ms clinics iraq january 2000 december 2018 cases diagnosed according mcdonalds criteria 2010 new cases diagnosed according new criteria mcdonalds criteria 2018 patients records reviewed scientific committeeresults study found 6851 ms females femaletomale ratio 2181 407 patients diagnosed reached 18 years age mean age 323 98 prevalence found 1173 100 000 162 100 000 among females 73 100 000 among males incidence 005 year 2000 15 year 2017 initial symptoms visual 3206 motor 2811 2558 sensory symptoms 8997 clinical form relapsing remitting ms rrms 8165 patients firstline treatment meanwhile 6697 cases diagnosed within weeks months symptom onset summer frequencies regarding birth seasonconclusions ms significantly increased incidence iraq prevalence low compared neighboring countries rrms common clinical form visual symptoms showed highest frequency first presenting symptomspmid34409919 doi101080 0161641220211952511,1.0
mrna covid19 vaccines increase shortterm risk clinical relapses multiple sclerosis j neurol neurosurg psychiatry 2021 aug 18jnnp2021327200 doi 101136 jnnp2021327200 online ahead printno abstractpmid34408003 doi101136 jnnp2021327200,0.0
effectiveness group resilience intervention people multiple sclerosis delivered via frontline services disabil rehabil 2021 aug 18111 doi 101080 0963828820211960441 online ahead printabstractpurpose study aims evaluate effectiveness acceptance commitment therapybased group resilience intervention resilience activities every day program ready delivered people ms pwms via frontline italian servicesmaterials methods singlearm longitudinal study nested qualitative study ready composed seven weekly inperson sessions 25h plus booster session five weeks later data collected immediately program booster session 3months followupresults thirtythree ready groups 237 participants run thirtythree trained psychologists participants improved resilience primary outcome anxiety depression stress healthrelated quality life hrqol psychological flexibility associated processes acceptance defusion values improvements outcomes occurred postintervention maintained 3month followup demographic illness variables predicted improvements psychological flexibility mediated improvements resilience anxiety depression stress hrqol qualitative data confirmed ready feasibility positive psychological impacts participantsconclusions study findings support ready effectiveness pwms broad applicability population delivery frontline servicesimplications rehabilitationready ms highly structured brief manualized group interventionit effective improving participants psychological functioning resilience anxiety depression stress hrqol psychological flexibility related act processes psychological flexibility mediated improvements resilience anxiety depression stress hrqolready can effectively delivered frontline services pwms without limitation terms participants demographic illness characteristicspmid34406895 doi101080 0963828820211960441,0.0
near visual signs symptoms multiple sclerosis compatible convergence insufficiency clin exp optom 2021 aug 1816 doi 101080 0816462220211961566 online ahead printabstractclinical relevance optometric management neurodegenerative diseases essential since visual signs double vision visual acuity reduction oculomotricity dysfunctions usually present subjects course disease present paper can guide clinicians better managing patients multiple sclerosisbackground patients multiple sclerosis present near vision symptoms may related binocular anomalies symptoms investigated related specific signs aim present study evaluate binocular vision subjects multiple sclerosis analyse near visual signs symptoms observed compatible found convergence insufficiency occurs neurodegenerative diseasesmethods total 57 multiple sclerosis patients 26 healthy controls examined classified potentially compatible convergence insufficiency according signs symptoms clinical diagnosis convergence insufficiency established subjects met following criteria npc breakpoint 6 cm pfv 15 baseout exophoria greater near distance least 4 convergence insufficiency symptom survey ciss administered assess symptomatology considering score 16 positiveresults according ciss score 54 4 multiple sclerosis subjects revised showed suspect convergence insufficiency median score 27 iqr 9 whereas one subject control group 38 showed suspect according diagnostic criteria based signs 158 multiple sclerosis patients real diagnosis convergence insufficiencyconclusion multiple sclerosis patients showed symptomatology compatible convergence insufficiency supported signs showed esophoric tendency discrepancies signs symptoms due questionnaire used including items also related cognitive function ocular abnormalitiespmid34406109 doi101080 0816462220211961566,0.0
neural correlates extrinsic intrinsic outcome processing learning individuals tbi pilot investigation brain imaging behav 2021 aug 18 doi 101007 s11682021005086 online ahead printabstractoutcome processing ability learn feedback important component adaptive behavior rehabilitation evidence healthy adults implicates striatum dopamine outcome processing animal research shows damage dopaminergic pathways brain can lead disruption dopamine tone transmission evidence thus suggests persons tbi experience deficits outcome processing however research directly investigated outcome processing associated neural mechanisms tbi examine outcome processing individuals tbi learning given tbi negatively impacts striatal dopaminergic systems hypothesize individuals tbi exhibit deficits learning outcomes test hypothesis individuals moderatetosevere tbi healthy adults presented declarative pairedassociate word learning task outcomes indicating performance accuracy presented immediately task performance form either monetary performancebased feedback two types feedback provided opportunity test whether extrinsic intrinsic motivational aspects outcome presentation play role learning outcome processing results show individuals tbi exhibited impaired learning feedback compared healthy participants additionally individuals tbi exhibited increased activation striatum outcome processing results study suggest outcome processing learning immediate outcomes impaired individuals tbi might related inefficient use neural resources task performance reflected increased activation striatumpmid34406636 doi101007 s11682021005086,0.0
identifying falls remotely people multiple sclerosis j neurol 2021 aug 17 doi 101007 s0041502110743y online ahead printabstractbackground falling common people multiple sclerosis ms tends underascertained undertreatedobjective evaluate fall risk people msmethods ninetyfour people ms able walk 2 min without assistive device expanded disability status scale edss 65 recruited clinicbased measures recorded baseline 1 year patientreported outcomes pros including fall survey ms walking scale msws12 completed baseline 15 3 6 9 12 months average daily step counts steps recorded using wristworn accelerometerresults 50 94 participants 532 reported falling least 56 participants reported fall research questionnaires medicalrecord documented falls fallers greater disability median edss 55 iqr 4060 versus 25 iqr 1540 p 0001 likely progressive ms p 0003 took fewer steps mean difference 1 979 p 0007 nonfallers stepwise regression revealed msws12 major predictor future fallsconclusions falling common people ms underreported underascertained neurologists clinic multimodal fall screening clinic remotely may help improve patient care identifying greatest risk allowing timely intervention referral specialized physical rehabilitationpmid34405267 doi101007 s0041502110743y,0.0
prioritization risk situations neurourology guidelines association franaise d#39 urologie afu association francophone internationale des groupes d#39 animation de la paraplgie afigap groupe de neurourologie de langue franaise genulf socit franaise de mdecine physique et de radaptation sofmer socit interdisciplinaire francophone d#39 urodynamique et de pelviprinologie sifudpp world j urol 2021 aug 17 doi 101007 s00345021038044 online ahead printabstractpurpose current health crisis drastically impacted patient management many fields including neurourology leading mandatory reorganization aim work establish guidelines regarding prioritization optimal timing step neurogenic lower urinary tract dysfunction managementmethods steering committee included urologists physical medicine rehabilitation practitioners based literature review expertise established comprehensive risksituation list built risk scale allowing multiple experts score clinical situation new recommendations generated using delphi process approachresults fortynine experts participated rating group among 206 initial items 163 selected divided four domains diagnosis assessment treatment followup complications two subdomains general applicable neurological conditions conditionspecific varying according neurological condition spinal cord injury multiple sclerosis brain injury parkinsonism dysraphism lower motor neuron lesions resulted guidelines expert opinions established panel frenchspeaking specialists limit scalability workconclusions present multidisciplinary collaborative work generates recommendations complement existing guidelines help clinicians reorganize patients list long term personalized medicine approach context health crisis notpmid34402945 doi101007 s00345021038044,0.0
factors determining treatment ineffectiveness multiple sclerosis neurol res 2021 aug 1619 doi 101080 0161641220211967680 online ahead printabstractbackground patients multiple sclerosis ms suboptimal response well evaluated every step treatmentreview summary determining patients moderate high activity suboptimal response treatment clinical variables mri activity perception patient physician side effects serious risks etc timely intervention treatment important achieving desired effectiveness long term within early stages limited time interval effective treatment ms patients time intervention critical achieve longterm positive results diagnosis early individualized specific treatment ms depending severity disease can prevent radiological physical disability medium long termconclusions emergence number new treatments benefits risks change nature interactions patients ms physicians anticipated will required patientrelated clinical decisionmaking process developing ms landscapepmid34396921 doi101080 0161641220211967680,1.0
modified mediterranean diet vs traditional iranian diet efficacy dietary interventions dietary inflammatory index score fatigue severity disability multiple sclerosis patients br j nutr 2021 aug 16135 doi 101017 s000711452100307x online ahead printabstractbackground current evidence suggests adherence mediterranean diet med can reduce inflammation chronic diseases however studies pertaining relapsingremitting multiple sclerosis rrms limited therefore aim study investigate potential modied med mmed improving dietary inflammatory index dii scores disability fatigue severity compared traditional iranian diet tid rrms patientsmethods initial screening n261 180 rrms patients randomized receive mmed tid control six months dii score expanded disability status scale edss 21item modified fatigue impact scale mfis evaluated baseline trial cessation multivariate analysis covariance conducted adjusted age gender body weight body mass index education level supplement use family history duration msresults 180 patients enrolled 147 participants included nal analysis n mmed68 n tid79 selfreported adherence good 81 dietary intakes 45 food parameters assessed food frequency questionnaire mmed significantly reduced dii scores six months 238021 187086 p0001 tid elicit changes 221044 214101 p0771 additionally mfis total score decreased significantly 724172 639142 p0001 whereas considerable improvement edss mmed groupconclusion adherence mmed six months improved dietary inflammatory status fatigue severity rrms patients however traditional iranian diet positively impact dietary inflammation mfis scorepmid34392854 doi101017 s000711452100307x,0.0
world brain day 2021 join us quot stop multiple sclerosisquot world federation neurology multiple sclerosis international federation collaboration can j neurol sci 2021 jun 2412 doi 101017 cjn2021147 online ahead printno abstractpmid34392849 doi101017 cjn2021147,0.0
clinical paraclinical correlates employment status multiple sclerosis neurol sci 2021 aug 15 doi 101007 s1007202105553z online ahead printabstractpurpose identify clinical paraclinical markers employment status multiple sclerosis ms methods crosssectional substudy investigating 1226 ms patients minimalized confounding effect two groups patients matched sex age education selected 307 patients full time employment 153 unemployed patients receiving disability pension explored associations employment status expanded disability status scale edss 25 foot walk test 25fwt nine hole peg test 9hpt brief international cognitive assessment ms bicams paced auditory serial addition test pasat beck depression inventory bdi sloan charts sloan brain volumetric mri measuresresults groups differed significantly variables interest p 0001 univariate analyses edss sdmt symbol digit modalities test adjusted bdi 25fwt 9hpt best explained variability vocational status multivariate analyses combination edss 25fwt sdmt bdi corpus callosum fraction ccf explained greatest variability next step patients matched edss differences sdmt 25fwt p 0001 9hpt ccf t2 lesion volume still present p 0005 groups best multivariate model consisted sdmt bdi t2 lesion volumeconclusions edss walking ability cognitive performance mri volumetric parameters independently associated employment statuspmid34392392 doi101007 s1007202105553z,0.0
validity 2 fall prevention strategy scales people stroke parkinson#39 s disease multiple sclerosis j geriatr phys ther 2021 aug 13 doi 101519 jpt0000000000000325 online ahead printabstractbackground purpose falls common persistent concern among people neurological disorders pwnd frequently result mobility deficits may lead loss functional independence study investigated ceiling floor effects internal consistency convergent validity 2 patientreported fall prevention strategy scales pwndmethods prospective cohort study twohundred ninetynine pwnd 111 people multiple sclerosis 94 people parkinsons disease 94 people stroke seen rehabilitation assessed number retrospective prospective falls use walking assistive devices scores fall prevention strategy survey fpss falls behavioural scale fab balance mobility scales berg balance scale dynamic gait index timed go 10m walking test activitiesspecific balance confidence analyzedresults total score distributions showed negligible ceiling floor effects fpss ceiling 03 floor 03 fab ceiling 0 floor 0 cronbach ci 087 085089 fpss 086 084088 fab terms convergent validity fpss fab moderately correlated spearman correlation coefficient 065 moreover correlations fpss fab balance mobility scales ranged 025 049 p 01 scales slightly better able distinguish retrospective fallers nonfallers area curve auc 95 ci fpss 061 0507 fab 060 0506 compared prospective fallers nonfallers auc 95 ci fpss 056 0406 fab 057 0406 scales accurately identified individuals typically required use walking assistive device daily ambulation auc 95 ci fpss 074 0708 fab 069 0607 multiple regression analysis showed previous falls use assistive device balance confidence significantly predicted participants prevention strategies fpss r2 031 f 8 159 105 p 01 fab r2 031 f 8 164 1089 p 01 conclusion fpss fab appear valid tools assess fall prevention strategies people neurological disorders scales provide unique added value providing information individual behavior fall preventionpmid34392263 doi101519 jpt0000000000000325,0.0
smoking obesity disability worsening ppms analysis informs original trial dataset j neurol 2021 aug 15 doi 101007 s0041502110750z online ahead printabstractbackground smoking obesity recognized modifiable risk factors associated higher ms incidence impact physical cognitive disability worsening less clearobjective investigate impact smoking obesity disability worsening primary progressive ms ppms methods used data informs clinicaltrialsgov identifier nct00731692 large randomizedcontrolled trial ppms compare significant worsening edss t25fw nhpt pasat smokers nonsmokers bmi groups 12 24 33 months followup investigated association smoking bmi screening risk disability worsening logistic regression modelsresults smokers significantly higher edss scores throughout trial edss significantly different bmi categories outcome measure significantly different smokers nonsmokers bmi categories throughout trial neither smoking status bmi associated significant worsening outcome measure time point followupconclusion despite known effects ms incidence smoking bmi associated risk physical cognitive disability worsening 3 years wellcharacterized ppms trial cohortpmid34392376 doi101007 s0041502110750z,0.0
sarscov2 antibodies multiple sclerosis patients depending vaccine mode action mult scler 2021 aug 1313524585211039128 doi 101177 13524585211039128 online ahead printno abstractpmid34387536 doi101177 13524585211039128,0.0
effect sarscov2 nervous system review neurological impacts caused human coronaviruses rev neurosci 2021 aug 13 doi 101515 revneuro20210041 online ahead printabstractthe covid19 pandemic affected millions people worldwide coronaviruses typically low rates neurotropic effects massive transmission sarscov2 suggests substantial population will suffer potential sarscov2related neurological disorders rapid recent emergence sarscov2 means little research exists potential neurological effects analyze effects similar viruses provide insight potential effects sarscov2 nervous system beyond seven coronavirus strains hcovoc43 hcovhku1 hcov229e hcovnl63 sarscov merscov sarscov2 can infect humans many strains cause neurological effects headaches dizziness strokes seizures critical illness polyneuropathy myopathy certain studies also linked coronaviruses multiple sclerosis extensive central nervous system injuries reviewing studies provides insight anticipated effects patients sarscov2 review will first describe effects coronaviruses caused severe disease sarscov merscov nervous system well proposed origins nonneurological effects neurological infection mechanisms will discuss known sarscov2 areas reference aforementioned viruses goal providing holistic picture sarscov2pmid34388333 doi101515 revneuro20210041,0.0
pregnancy patients multiple sclerosis j investig med 2021 aug 12jim2020001609 doi 101136 jim2020001609 online ahead printabstractmultiple sclerosis ms autoimmune disorder affects 25 million people globally women reproductive age highly susceptible disease study aims explore association ms pregnancy articles related topic investigation identified search terms included pregnancy multiple sclerosis ms women articles published 2010 2020 included review review shows researchers attempted explore link pregnancy ms results previous studies indicate pregnancy reduces risk ms relapse however evidence suggesting pregnancy can affect longterm progression ms lacking research results also indicate ms increase risk maternal fetal complications ms remains serious autoimmune disorder affects many women worldwide data gathered review indicate significant correlation exists pregnancy ms relapse rates findings presented review can aid management ms pregnancy furthermore research results provide vital insights caregivers can use monitor patients ms pregnancypmid34385291 doi101136 jim2020001609,0.0
multiple sclerosis plaques may undergo continuous myelin degradation crosssectional study myelin axonrelated quantitative magnetic resonance imaging metrics neuroradiology 2021 aug 12 doi 101007 s00234021027810 online ahead printabstractpurpose hypothesize myelin susceptible damage time axons investigated association estimated duration onset multiple sclerosis ms plaques myelin axonrelated quantitative synthetic magnetic resonance imaging symri neurite orientation dispersion density imaging noddi metricsmethods analyzed 31 patients ms 73 newly appeared plaques simple linear regression analysis performed assess association estimated duration onset plaques quantitative mri metrics metrics included myelin volume fraction mvf axon volume fraction gratio plaque normalappearing white matterresults ms plaques longer estimated duration onset significantly correlated lower mvf slope 00070 r2 00970 higher gratio slope 00078 r2 00842 p values 005 conclusion results suggested myelin plaques undergoes continuous damage axons myelin imaging symri noddi may useful quantitative assessment temporal changes ms plaquespmid34383123 doi101007 s00234021027810,1.0
acute attack patient multiple sclerosis 2 days covid vaccination case report acta neurol belg 2021 aug 11 doi 101007 s13760021017752 online ahead printno abstractpmid34382145 doi101007 s13760021017752,0.0
anticd20 therapies multiple sclerosis current status future perspectives j neurol 2021 aug 11 doi 101007 s0041502110744x online ahead printabstractmultiple sclerosis ms chronic inflammatory demyelinating neurodegenerative disease affecting central nervous system cns often characterized accumulation irreversible clinical disability time last years dramatic evolution several key concepts immune pathophysiology ms treatment disease demonstration strong efficacy good safety profile selective bcelldepleting therapies anticd20 monoclonal antibodies significantly expanded therapeutic scenario relapsing progressive ms patients identification new therapeutic target key role b cells triggering ms disease also pointed determining shift traditional view ms activity largely tcell mediated notion msrelated pathological processes involve bidirectional interactions several immune cell types including b cells periphery cns review provides updated overview involvement b cells immune pathophysiology pathology ms summarize rationale regarding use anticd20 therapies results main randomized controlled trials observational studies investigating efficacy safety profile rituximab ocrelizumab ofatumumab ublituximab suggestions regarding vaccinations management ms patients covid19 pandemic anticd20 therapies also discussed finally therapies investigation future perspectives anticd20 therapies taken considerationpmid34382120 doi101007 s0041502110744x,1.0
systematic review resting state functional mri connectivity changes cognitive impairment multiple sclerosis brain connect 2021 aug 12 doi 101089 brain20210104 online ahead printabstractintroduction cognitive impairment multiple sclerosis ms increasingly investigated resting state functional mri rsfmri functional connectivity fc however results remain difficult interpret showing high low fc associated cognitive impairment conducted systematic review rsfmri studies ms understand whether direction fc change relates cognitive dysfunction may influenced choice methodologymethods embase medline psycinfo searched studies assessing cognitive function rsfmri fc adults msresults fiftyseven studies included narrative synthesis 50 found association cognitive impairment fc abnormalities worse cognition linked high fc 18 studies low fc 17 studies nine studies found patterns high low fc related poor cognitive performance different regions different mr metrics clear link increased fc early stages ms reduced fc later stages predicted common models ms pathology throughout found substantial heterogeneity study methodology carefully consider may impact observed findingsdiscussion results indicate urgent need greater standardisation field terms choice mri analysis definition cognitive impairment will allow us use rsfmri fc biomarker future clinical studies tool understand mechanisms underpinning cognitive symptoms mspmid34382408 doi101089 brain20210104,0.0
prediagnostic neurofilament light chain levels amyotrophic lateral sclerosis neurology 2021 aug 11101212 wnl0000000000012632 doi 101212 wnl0000000000012632 online ahead printabstractobjective assess whether plasma neurofilament light chain nfl levels elevated als diagnosis evaluate whether prediagnostic nfl levels associated metabolic alterationsmethods conducted matched casecontrol study nested three large prospective us cohorts nurses health study health professionals followup study multiethnic cohort study identified 84 individuals developed als followup available plasma samples prior disease diagnosis als case randomly selected controls alive time case diagnosis matched birth year sex race ethnicity fasting status cohort time blood draw measured nfl plasma samples used conditional logistic regression estimate rate ratios rrs 95 confidence intervals cis als adjusting body mass index smoking physical activity urate levelsresults higher nfl levels associated higher als risk plasma samples collected within 5 years als diagnosis rr per 1 standard deviation sd increase 268 95 ci 118608 samples collected away diagnosis rr per 1 sd increase 116 95 ci 078173 total 21 metabolites correlated prediagnostic nfl levels als cases p 005 none remained significant multiple comparison adjustmentsconclusions plasma nfl levels elevated prediagnostic als cases indicating nfl may useful biomarker already earliest stages diseaseclassification evidence study provides class ii evidence plasma nfl levels elevated prediagnostic als patientspmid34380747 doi101212 wnl0000000000012632,0.0
cd19 + cd21 lo neg cells increased systemic sclerosisassociated interstitial lung disease clin exp med 2021 aug 10 doi 101007 s10238021007455 online ahead printabstractinterstitial lung disease ild represents significant cause morbidity mortality systemic sclerosis ssc purpose study examine recirculating lymphocytes ssc patients potential biomarkers interstitial lung disease ild peripheral blood mononuclear cells pbmcs isolated patients ssc healthy controls enrolled vanderbilt university myositis scleroderma treatment initiative center cohort 9 20176 2019 clinical phenotyping performed chart abstraction immunophenotyping performed using mass cytometry fluorescence cytometry combined tdistributed stochastic neighbor embedding analysis traditional biaxial gating study included 34 patients sscild 14 patients without sscild 25 healthy controls cd21lo neg cells significantly increased sscild ssc without ild 154 133 vs 58 09 p 0002 healthy controls 50 05 p 00001 cd21lo neg b cells can identified single biaxial gate tsne analysis reveals biaxial gate comprised multiple distinct subsets increased sscild cd21lo neg cells healthy controls sscild predominantly tbet positive intracellular cd21 immunohistochemistry staining demonstrated cd21lo neg b cells diffusely infiltrate lung parenchyma sscild patient additional work needed validate biomarker larger cohorts longitudinal studies understand role cells sscildpmid34374937 doi101007 s10238021007455,0.0
relationship type skin lesions nailfold capillaroscopy pattern mixed connective tissue disease clin rheumatol 2021 aug 9 doi 101007 s10067021057174 online ahead printabstractintroduction mixed connective tissue disease mctd rare disease clinical picture consisted multiple organ manifestations including skin changes resembling systemic lupus erythematosus sle systemic sclerosis ssc dermatomyositis dm background manifestations microvascular changes alteration endothelial function impairment endothelial progenitor cell nailfold capillaroscopy nfc simple noninvasive technique investigating microvascular involvement rheumatic diseasesobjectives describe relationship type skin lesions nfc pattern mctd patientsmethods analyzed clinical picture nfc patterns 79 patients mctd nfc changes classified normal early active late sclerodermalike patterns sdlike pattern based cutolo classification patients subjective physical examinations carried specifically occurrence skin lesions course mctd assessed systemic sclerosislike ssclike systemic lupus erythematosuslike slelike dermatomysitislike dmlike results skin changes present 64 81 patients involving 43 54 slelike 48 61 ssclike 4 51 dmlike nfc changes observed total 55 696 patients predominance early pattern 41 519 patients according skin change phenotypes nfc changes observed 31 72 patients slelike 32 667 patients ssclike skin phenotypes early pattern predominated groupconclusions find correlation nfc pattern type skin changes key points study show correlation presence absence skin lesions nfc pattern sclerodermalike patterns found 60 patients mixed connective tissue disease early pattern dominant regardless occurrence absence skin lesions patients mctd skin lesions regardless type sle ssc correlate type lesion found nfc examinationpmid34370129 doi101007 s10067021057174,0.0
job satisfaction among physicians nurses involved management multiple sclerosis role happiness meaning work neurol sci 2021 aug 7 doi 101007 s10072021055208 online ahead printabstractobjective health professionals caring persons multiple sclerosis ms faced increasingly complex working conditions can undermine job satisfaction quality healthcare services aim study delve health professionals job satisfaction assessing predictive role happiness meaning work specifically hypothesized job meaning moderate relationship job happiness satisfactionmethods study hypothesis tested among 108 healthcare professionals 53 physicians 55 nurses working eight ms centers italy participants administered eudaimonic hedonic happiness investigation job satisfaction questionnaire hierarchical regression analysis performed test moderating role job meaning job happiness satisfactionresults significant interaction effect job happiness meaning job satisfaction identified physicians nurses work attributed low meaning participants experiencing high job happiness satisfied work reporting low happiness contrast work perceived highly meaningful participants levels job happiness significantly contribute job satisfactionconclusions focusing interplay job happiness meaning findings bring forward practical suggestions preservation promotion job satisfaction among health professionals working ms patients particularly suggest need strengthen jobrelated aspects may enhance job meaning thus providing health professionals significant reasons persevere work face daily challengespmid34363548 doi101007 s10072021055208,0.0
vivo implementation mex mri myelin fraction mice brain magma 2021 aug 6 doi 101007 s1033402100950z online ahead printabstractobjective magnetization exchange mex sequence measures signal linearly dependent myelin proton fraction selective suppression water magnetization recovery period varying recovery period enables extraction percentile fraction myelin bound protons aim demonstrate mex sequence sensitivity fraction protons associated myelin mice brain vivomethods cuprizone mouse model used manipulate myelin content mice fed cuprizone n 15 normal chow n 8 imaged vivo using mex sequence mr images segmented corpus callosum internal capsule white matter cortical gray matter fitted recovery equation results analyzed correlation mwf histopathologyresults extracted parameters show significant differences corpus callosum cuprizone control groups cuprizone group exhibited reduced myelin fraction 265 p 001 gray matter values less affected 135 reduction p 005 changes detected internal capsule results validated mwf scans good correlation histology analysis r2 0685 conclusion results first vivo implementation mex sequence provide quantitative measure demyelination brain white matterpmid34357453 doi101007 s1033402100950z,1.0
ampk brain roles glucose neural metabolism febs j 2021 aug 6 doi 101111 febs16151 online ahead printabstractthe adenosine monophosphateactivated protein kinase ampk integrative metabolic sensor maintains energy balance cellular level plays important role orchestrating intertissue metabolic signaling ampk regulates cell survival metabolism cellular homeostasis basally well response various metabolic stresses studies far show ampk pathway associated neurodegeneration cns pathology mechanisms involved remain unclear ampk dysregulation reported neurodegenerative diseases amyotrophic lateral sclerosis multiple sclerosis alzheimers disease parkinsons disease huntingtons disease neuropathies ampk activation appears neuroprotective proapoptotic possibly dependent upon neural cell types nature insults intensity duration ampk activation embryonic brain development ampk null mice appears proceed normally without overt structural abnormalities recent study confirmed full impact ampk loss postnatal aging brain studies revealed ampk deletion neurons increased basal neuronal excitability reduced latency seizure upon stimulation three major pathways glycolysis pentose phosphate shunt glycogen turnover contribute utilization glucose brain ampks regulation aerobic glycolysis astrocytic metabolism warrants deliberation particularly glycogen turnover shuttling glucose glycogenderived lactate astrocytes neurons activation minireview focus recent advances ampk energysensing brainpmid34355526 doi101111 febs16151,1.0
qualitative investigation reasoning behind decisions decline participation research intervention studywithinatrial j health psychol 2021 aug 613591053211037736 doi 101177 13591053211037736 online ahead printabstractthe current studywithinatrial explored individuals decisions decline participation research trialling chronic illnessfocused therapy ie multiple sclerosis four themes identified seven semistructured interviews participation decliners confirmed host trials patient public involvement ppi panel acknowledgement value research fit study misinterpretation participant information ignorance bliss discussed light theory research studywithinatrial extends research trial recruitment participation decline also suggesting ppi can utilised practical impactful mannerpmid34355599 doi101177 13591053211037736,0.0
walleyed bilateral internuclear ophthalmoplegia associated etanercept pract neurol 2021 aug 5practneurol2021003064 doi 101136 practneurol2021003064 online ahead printno abstractpmid34353861 doi101136 practneurol2021003064,0.0
experience women multiple sclerosis sexuality disabil rehabil 2021 aug 517 doi 101080 0963828820211925750 online ahead printabstractpurpose understand women multiple sclerosis ms experience sexualitymaterial methods qualitative study eight women belonging ms associations elche alicante spain completed semistructured interviews subsequently carried thematic analysis dataresults four main themes multiple subthemes identified first theme influence stereotypes sexual expression included social gender perspectives second theme physical emotional causes sexual dysfunction classified primary secondary tertiary third theme experiencing sexuality personalised way included relationships partner concept sexuality resources improving sexual function final theme external support included sexual assistance professional care peer supportconclusions sexual needs change women ms diagnosis disease however addressed routinely health professionals search resources women ms highlighted support partners associations constitute support network expression sexualityimplications rehabilitationwomen ms refer changes sexual function changes addressed routinely healthcare providersinclusion sexual partners women ms consultations regarding treatment sexual dysfunctions considered previous consentthe positive experience woman ms used sexual assistant services may justify researchms associations can also play important role sexual field meeting place peers shared experiencespmid34352184 doi101080 0963828820211925750,0.0
disorders vision multiple sclerosis clin exp optom 2021 aug 4110 doi 101080 0816462220211947745 online ahead printabstractmultiple sclerosis ms neurological inflammatory disorder known attack heavily myelinated regions nervous system including optic nerves cerebellum brainstem spinal cord review will discuss clinical manifestations investigations ms similar neurological inflammatory disorders affecting vision well effects ms treatments vision assessment visual pathways critical considering ms can involve multiple components visual pathway including optic nerves uvea retina occipital cortex optical coherence tomography increasingly recognised highly sensitive tool detecting subclinical optic nerve changes magnetic resonance imaging mri critical ms diagnosis predicting longterm disability optic neuritis ms involves unilateral vision loss characteristic pain eye movement visual loss neuromyelitis optica spectrum disorder tends severe preferential altitudinal field loss chiasmal tract lesions also common differential diagnoses include chronic relapsing inflammatory optic neuropathy giant cell arteritis lebers hereditary optic neuropathy affects young males visual loss tends painless subacute typically involving optic nerves ms lesions vestibulocerebellum brainstem thalamus basal ganglia may lead abnormalities gaze saccades pursuit nystagmus can identified eye examination medial longitudinal fasciculus lesions can cause another frequent presentation ms internuclear ophthalmoplegia failure ipsilateral eye adduction contralateral eye abduction nystagmus treatments ms include highdose corticosteroids acute relapses diseasemodifying medications relapse prevention therapies may also adverse effects vision including central serous retinopathy corticosteroid therapy macular oedema fingolimodpmid34348598 doi101080 0816462220211947745,1.0
comparison visual evoked potentials patients affected optic neuritis multiple sclerosis neuromyelitis optica spectrum disorder j neuroophthalmol 2021 jul 27 doi 101097 wno0000000000001285 online ahead printabstractpurpose compare visual evoked potentials veps optic neuritis patients multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd controls evaluate correlations vep optical coherence tomography oct contrast sensitivity cs automated perimetrymethods fiftyfive eyes 29 patients ms 14 nmosd 15 57 eyes 29 controls evaluated using vep automated perimetry cs optical coherence tomography three groups analyzed 1 ms eyes history onms 2 nmosd eyes onnmosd 3 healthy controls groups compared associations parameters testedresults compared controls onms eyes showed significantly delayed n75 p100 latencies using mediumsized stimulus 30 delayed p100 latency using large stimulus 15 similar amplitudes compared controls onnmosd eyes showed significantly lower n75 p100 amplitudes stimulus sizes p100 n135 amplitudes 30 stimulus latencies differ except delayed p100 latency 30 stimulus comparing 2 groups using 15 stimulus significant delay p100 latency onms eyes reduction n75 p100 amplitude onnmosd eyes peripapillary retinal nerve fiber layer macular inner retinal layers cs measurements significantly smaller patients controls strong correlation found vep parameters inner retinal layer thickness onnmosd eyesconclusions onms eyes normal amplitude delayed vep latency whereas onnmosd eyes displayed reduced amplitude preserved latency elicited checkerboard stimulus large 15 checks conditions vep may help distinguish resolved msrelated resolved nmosdrelated onpmid34348361 doi101097 wno0000000000001285,0.0
prevalence predictors bowel dysfunction large multiple sclerosis outpatient population italian multicenter study j neurol 2021 aug 4 doi 101007 s0041502110737w online ahead printabstractintroduction bowel dysfunction bd reported common disabling symptom multiple sclerosis ms patients date studies explored prevalence symptoms large multicenter outpatient setting aims present study assess prevalence bd large multicenter italian ms population ii correlation clinicodemographic variables severity bdmethods nine participating center screened ms patients prospectively 1100 subjects enrolled patients underwent expanded disability status scale edss completed neurogenic bowel dysfunction score nbds multivariable linear logistic regression models used assess association nbds several clinicodemographic variablesresults fourteen percent ms patients showed moderate severe bd nbds 10 percentage increased patients high disability ranging 26 32 moderate severe bd frequent ms patients progressive phenotypes higher disability older age longer disease duration nbds severity predicted female sex ambulation impairment bladder symptomsconclusion study confirms relatively high prevalence moderate severe bd large multicenter unselected outpatient ms population bd appears mainly associated female sex msrelated disabilitypmid34347149 doi101007 s0041502110737w,0.0
moderators improvements fatigue impact following selfmanagement intervention multiple sclerosis secondary analysis randomized controlled trial j phys med rehabil 2021 aug 3 doi 101097 phm0000000000001861 online ahead printabstractfatigue one common disabling symptoms multiple sclerosis ms recent randomized controlled trial comparing fatigue selfmanagement program general ms education program found programs improved fatigue participants ms participants randomized selfmanagement program fatigue take control n 109 ms education program ms take control n 109 secondary analysis trial used multilevel moderation analysis examine moderators treatmentrelated effects fatigue modified fatigue impact scale baseline 6month followup following potential treatment moderators examined age sex cohabitation marital status baseline levels selfefficacy depression symptoms sleep quality cohabitation status living without spouse partner interacted intervention group time predict fatigue impact p 04 fatigue take control participants lived spouse partner showed marginal effect greater rate improvement fatigue compared lived alone p 08 however rates improvement fatigue ms take control participants similar living without spouse partner findings suggest living spouse partner may facilitate benefit selfmanagement interventions msrelated fatigue future research investigate contribution supportive others selfmanagement fatigue mspmid34347626 doi101097 phm0000000000001861,0.0
reliability validity turkish version telemedicine satisfaction usefulness questionnaire tsuq telemedicine patient questionnaire tpq individuals multiple sclerosis neurol sci 2021 aug 3 doi 101007 s10072021055191 online ahead printabstractobjective study aimed translate adapt telemedicine satisfaction usefulness questionnaire tsuq telemedicine patient questionnaire tpq turkish thereafter analyze psychometric properties questionnairesmethods total 149 multiple sclerosis ms patients recruited study 4 years patients supervised department clinician using telemedicine cronbachs alpha coefficient used assess internal consistency evaluating scores 41 retested patients 1 week later testretest reliability determined using intraclass correlation coefficient icc pearsons correlation coefficient used assess construct validity r results total 149 patients 103 women 46 men mean age 409109 years included study ms duration patients 915624 years internal consistency items total score tsuq excellent 080 ranged 09710974 hand internal consistency items total score tpq excellent either 080 ranged 08780890 icc tsuqs tpqs total score excellent 080 correlation tsuq tpq strong r0734 p001 addition moderate relationship tsuq beck depression scale bds r0363 p001 hand low correlation tpq bds r0217 p005 conclusion turkish version tsuq tpq valid reliable individuals mspmid34342782 doi101007 s10072021055191,0.0
outcome measures assisting treatment optimization multiple sclerosis j neurol 2021 aug 2 doi 101007 s00415021106748 online ahead printabstractobjective review instruments used assess disease stability progression persons multiple sclerosis pwms can guide clinicians optimizing therapymethods nonsystematic review scientific literature undertaken explore modalities monitoring symptoms disease evolution msresults multiple outcome measures tools developed use ms research well clinical management pwms beginning expanded disability status scale introduced 1983 clinicians researchers developed monitoring modalities assess aspects ms neurological impairment causesconclusions much progress made recent decades management ms evaluation disease progression new technology wearable sensors will provide new opportunities better understand changes function dexterity cognition essential work decades since edss introduced continues improve ability treat debilitating diseasepmid34338857 doi101007 s00415021106748,0.0
discrepancies selfreported devicemeasured sleep parameters adults multiple sclerosis j clin sleep med 2021 aug 2 doi 105664 jcsm9586 online ahead printabstractstudy objectives sleep problems common consequence multiple sclerosis ms however limited evidence regarding agreement devicemeasured selfreported sleep parameters adults ms present study examined agreement selfreported devicemeasured parameters sleep quality sample adults msmethods participants n49 completed sevenday sleep diary wore wristworn actigraph gt3x+ seven consecutive nights quantify selfreported devicemeasured sleep parameters respectivelyresults significant discrepancy selfreported devicemeasured parameters total time bed mean difference198 513 min sleep onset latency mean difference222 195 min frequency awakenings night mean difference128 68 intraclass correlation icc estimates indicated poor agreement methods parameters except total time bed icc080 blandaltman plots suggested total time bed total sleep time acceptable levels agreement linear regression analyses indicated sleep onset latency f11391 b134 p0001 number awakenings f54334 b185 p0001 sleep efficiency f1839 b077 p0001 significant proportional biasconclusions results draw attention discrepancies sleep parameter measurements highlight importance including selfreport devicemeasured outcomes complete accurate representation sleep adults mspmid34338630 doi105664 jcsm9586,0.0
massage therapy complementary alternative approach people multiple sclerosis systematic review disabil rehabil 2021 aug 1112 doi 101080 0963828820211949051 online ahead printabstractpurpose multiple sclerosis ms causes range different symptoms patients ms pwms looked alternative therapies control ms progress treat symptoms noninvasive therapeutic approaches massage can benefits mitigate symptoms however rigorous review massage effectiveness pwms present systematic review aims examine effectiveness different massage approaches common ms symptoms including fatigue pain anxiety depression spasticitymaterials methods systematic search related trials conducted electronic databases including cochrane library pubmed scopus web science google scholar using search terms related multiple sclerosis massage therapy pedro scale used evaluate methodological quality reviewed studiesresults total 12 studies met inclusion criteria rated 5 studies fair 7 studies good fatigue improved different massage styles reflexology nonspecific therapeutic massage swedish massage pain anxiety depression effectively improved reflexology techniques spasticity reduced swedish massage reflexology techniquesconclusions different massage approaches effectively improved ms symptoms fatigue pain anxiety depression spasticityimplications rehabilitationthe present review results indicate massage may beneficial effects motor nonmotor symptoms msmassage considered complementary alternative treatment combined conventional medicine people mspain fatigue best improved swedish massage anxiety depression effectively improved reflexologypmid34338108 doi101080 0963828820211949051,0.0
systematic review participant characteristics theorybased bahavior change interventions physical activity multiple sclerosis missing greatest potential lifelong benefits disabil rehabil 2021 jul 31120 doi 101080 0963828820211954705 online ahead printabstractpurpose study examined participant characteristics particularly disease duration theorybased physical activity behavior change trials multiple sclerosis ms summarized theoretical frameworks changes physical activity outcomesmaterials methods pubmed cinahl embase scopus searched identify potential trials one reviewer screened titles abstracts two reviewers independently screened fulltext articles based predetermined eligibility criteria data extracted one reviewer checked second reviewerresults among 33 trials reviewed one trial reported mean disease duration less five years ie 45 years sample remaining trials included samples mean disease duration 67 years longer common theories used social cognitive theory transtheoretical model motivational interviewing effects physical activity heterogeneous devicemeasured outcomes increased 414 studies selfreported outcomes improved 724 adherence 80 reported 345 studiesconclusions little focus persons ms early disease course physical activity behavior change interventions future research include comprehensive theoretical approaches homogeneous effects across outcome measures targeting early stage ms populationsimplications rehabilitationtheorybased physical activity behavior change interventions included persons multiple sclerosis ms early disease course 5 years since diagnosis disease duration criterion used include exclude participants reviewed theorybased behavior change interventions physical activity people msthe theorybased behavior change interventions review positively affected shortterm physical activity levels people mspmid34334057 doi101080 0963828820211954705,0.0
autoantibodies nmda receptor 1 modify rather cause encephalitis mol psychiatry 2021 jul 30 doi 101038 s41380021012383 online ahead printabstractthe etiology pathogenesis antinmethyldaspartatereceptor nmdar encephalitis role autoantibodies ab condition still obscure nmdar1ab exert nmdarantagonistic properties receptor internalization firm evidence exists date nmdar1ab induce brain inflammation encephalitis nmdar1ab immunoglobulin classes highly frequent across mammals multiple possible inducers boosters hypothesized nmdar encephalitis results primary brain inflammation coinciding presence nmdar1ab may shape encephalitis phenotype thus tested whether following immunization cocktail 4 nmdar1 peptides induction spatially temporally defined sterile encephalitis diphtheria toxinmediated ablation pyramidal neurons dta mice modify aggravate ensuing phenotype addition tried replicate recent report claiming immunizing just nmdar1n368 g369 region induced brain inflammation mice dta induction revealed syndrome comprising hyperactivity hippocampal learning memory deficits prefrontal cortical network dysfunction lasting blood brainbarrier impairment brain inflammation mainly hippocampal cortical regions pyramidal neuronal death microgliosis astrogliosis modest immune cell infiltration regional atrophy relative increases parvalbuminpositive interneurons presence nmdar1ab enhanced hyperactivity psychosislike phenotype whereas readouts identical controlimmunized dta mice nondta mice without nmdar1ab free encephalitic signs replication reported nmdar1n368 g369immunizing protocol two large independent cohorts wildtype mice completely failed conclude nmdar1ab can contribute behavioral phenotype underlying encephalitis induction encephalitis nmdar1ab remains provenpmid34331009 doi101038 s41380021012383,0.0
application deeplearning seronegative side nmo spectrum j neurol 2021 jul 30 doi 101007 s0041502110727y online ahead printabstractobjectives apply deeplearning algorithm brain mris seronegative patients neuromyelitis optica spectrum disorders nmosd nmosdlike manifestations assess whether structural features similar aquaporin4seropositive nmosd multiple sclerosis ms patientspatients methods analyzed 228 t2 t1weighted brain mris acquired aquaporin4seropositive nmosd n 85 ms n 95 aquaporin4seronegative nmosd n 11 three antimyelin oligodendrocyte glycoprotein antibodies mog aquaporin4seronegative patients nmosdlike manifestations idiopathic recurrent optic neuritis myelitis n 37 recruited february 2010 december 2019 seventythree percent aquaporin4seronegative patients nmosdlike manifestations also clinical followup median duration 4 years deeplearning neural network architecture based four 3d convolutional layers trained validated mri scans aquaporin4seropositive nmosd ms patients applied aquaporin4seronegative nmosd nmosdlike manifestations assignment unclassified aquaporin4seronegative patients compared clinical followupresults final algorithm differentiated aquaporin4seropositive nmosd ms patients accuracy 095 aquaporin4seronegative nmosd 36 37 aquaporin4seronegative patients nmosdlike manifestations classified nmosd antimog patients similar probability nmosd ms clinical followup one unclassified aquaporin4seronegative patient evolved ms three developed nmosd others change phenotypeconclusions findings support inclusion aquaporin4seronegative patients nmosd suggest possible expansion aquaporin4seronegative unclassified patients nmosdlike manifestations antimog patients likely intermediate brain features nmosd mspmid34328544 doi101007 s0041502110727y,1.0
exercise training improves participation persons multiple sclerosis systematic review metaanalysis j sport health sci 2021 jul 26s20952546 21 000892 doi 101016 jjshs202107007 online ahead printabstractobjectives previous studies examined effects exercise training international classification functioning disability health icf component levels persons multiple sclerosis ms effects exercise training participation remains unclear objectives review 1 systematically characterize use outcome measures capture participation exercise training studies 2 quantify effect exercise training participation persons msmethods search 6 electronic databases cinahl sport discuss embase medline cochrane central scopus conducted identify controlled noncontrolled trials involving exercise training participation persons ms search strings built medical subject headings mesh cinahl headings icf linking rules used identify participation chapters categories captured metaanalysis used quantify effect exercise training participation randomized controlled trials rcts comparing exercise effects intervention usual careresults fortynine articles involving controlled noncontrolled exercise trials included systematic review outcome measures sixteen different outcome measures captured 9 participation chapters 89 unique participation categories identified across 16 outcome measures mobility represented participation chapter 108 items subsample 23 rcts included metaanalysis overall effect 060 standard error 012 95 confidence interval 037084 z 49 p 0001 calculated indicating moderate positive effect exercise training participationconclusion current review provides information can used guide selection outcome measures capture participation studies exercise training persons ms exercise training positive effect outcomes capture participation providing evidence role exercise training promoting maintaining engagement everyday lifepmid34325022 doi101016 jjshs202107007,0.0
statins risk amyotrophic lateral sclerosis systematic review metaanalysis acta neurol belg 2021 jul 28 doi 101007 s13760021017538 online ahead printabstractamyotrophic lateral sclerosis als paralytic heterogeneous progressive disease characterized degeneration upper lower motor neurons several studies effects statins drug risk als showed contradictory results evidence inconclusive aimed perform metaanalysis previous studies clarify association statin use risk als databases including pubmed scopus web science searched february 2021 studies reported association statin use risk als eligible studies provide report effect statin incidence als comparing control group articles low statin exposure time absence control group unknown number als patients excluded rate ratio 95 confidence interval ci used association measures casecontrol cohort studies fulltext abstract review data 8 studies total 547 622 participants 13 890 cases als entered present metaanalysis combined eight studies using randomeffect model rr statin users among groups 098 95 ci 080120 indicates association statin incidence als also high heterogeneity detected across studies q value 2662 p 00 i2 7271 metaanalysis study found association statin use increase als incidence result line previous studies provides strong evidence denies possible association statin uptake disease inductionpmid34322852 doi101007 s13760021017538,0.0
neurocognitive performance relapsingremitting multiple sclerosis patients associated metabolic abnormalities thalamus hippocampus gabaedited 1h mrs study neurol res 2021 jul 2718 doi 101080 0161641220211956282 online ahead printabstractobjectives multiple sclerosis ms inflammatory demyelinating disease may cause physical disabling well cognitive dysfunction presented study investigated neuropsychological status depends thalamus hippocampuss metabolic processes using aminobutyric acidedited magnetic resonance spectroscopy gabaedited 1h mrs patients early ms results differ healthy volunteersmethods recruited 36 relapsingremitting rrms ms patients 22 controls con addition common 1h mrs metabolites nacetylaspartate tnaa myoinositol mins total choline creatine tcr tcho also evaluated gaba glutamate glutamine glx metabolite ratios correlated results singledigit modality test sdmt expanded disability status score edss results thalamus gaba ratios gaba tcr gaba tnaa significantly lower rrms patients con tcho minsratios correlated lower scores sdmt edss metabolic ratios hippocampus differ rrms con correlate performed testsdiscussion study first provide gabaedited 1h mrs evidence msrelated metabolic changes thalamus hippocampus findings underline importance evaluating subcortical grey matter ms patients improve understanding clinical manifestations ms potential future target treatmentpmid34313578 doi101080 0161641220211956282,1.0
nutritional status relapsingremitting multiple sclerosis rrms patients compared healthy people turkish hospitalbased study nutr neurosci 2021 jul 2619 doi 101080 1028415x20211956253 online ahead printabstractobjective study compares nutritional status physical activity levels relapsingremitting multiple sclerosis rrms patients healthy peoplemethod study included 120 participants 60 multiple sclerosis ms patients 60 controls rrms diagnoses made based 2017 mcdonald criteria food intake frequency questionnaire administered participants threeday food intake records collected activity levels determined anthropometric measurements made differences groups analyzed using mannwhitney u test pearsons exact chisquared testresults participants ms 467 significantly lower rate shopping food compared control group 683 p 0002 ms group 33 lower rate intake green leafy vegetables 5 times weekly frequently control group 200 p 005 control group 350 higher consumption rate pastry 1 2 times monthly ms group 133 p 005 participants ms higher intake fiber insoluble fiber omega 3 fatty acid control group p 005 expanded disability status scale edss scores indicates positive correlation found daily intake fiber insoluble fiber p 005 patients ms inactive group higher edss median 200 000 500 minimal active group 125 000 400 p 0034 conclusion increase disability ms patients physical activity levels decrease becomes difficult shop addition consumption frequency green leafy vegetables take time prepare source fiber also decreasing shown fiber intake decreases disability increase therefore preventing progression disability ms patients important ensuring diversity food consumptionpmid34311682 doi101080 1028415x20211956253,0.0
employing connectomebased models predict working memory multiple sclerosis brain connect 2021 jul 26 doi 101089 brain20210037 online ahead printabstractbackground individuals multiple sclerosis ms vulnerable deficits working memory search neural correlates working memory within circumscribed areas inconclusive given widespread neural alterations observed ms predictive modeling approaches capitalize wholebrain connectivity may better capture individual differences working memorymethods applied connectomebased predictive modeling fmri data working memory tasks two independent samples relapsingremitting ms internal sample ninternal 36 crossvalidation used train model predict accuracy paced visual serial addition test functional connectivity hypothesized msspecific model successfully predict performance nback task validation cohort nvalidation 36 additionally assessed generalizability existing working memory networks derived healthy young adults samples explored anatomical differences healthy ms networksresults successfully derived msspecific predictive model working memory internal sample full rs 47 permuted p 011 predictions significant validation cohort rs 047 p 78 mse 006 r2 221 contrast healthy networks successfully predicted working memory ms samples internal rs 33 p 049 mse 009 r2 134 validation cohort rs 46 p 005 mse 005 r2 169 demonstrating translational potentialdiscussion functional networks identified large sample healthy individuals predicted significant variance working memory ms networks derived small samples people ms may limited generalizability potentially due diseaserelated heterogeneity robustness models derived large clinical samples warrants investigationpmid34309408 doi101089 brain20210037,0.0
wheelchair locomotion interface vr disability simulation reduces implicit bias ieee trans vis comput graph 2021 jul 26 pp doi 101109 tvcg20213099115 online ahead printabstractthis research investigates experiencing virtual embodiment wheelchair affects implicit bias towards people use wheelchairs also investigate receiving information virtual instructor uses wheelchair affects implicit bias towards people use wheelchairs implicit biases actions judgments people towards various concepts stereotypes eg races hypothesized experiencing disability simulation ds avatar wheelchair receiving information instructor disability will significant effect participants ability recall disabilityrelated information will reduce implicit biases towards people use wheelchairs investigate hypothesis 2x2 betweensubjects user study conducted participants experienced immersive vr ds presents information multiple sclerosis ms factors instructor ie instructor disability vs instructor without disability locomotion interface ie without disability locomotion inplacewalking disability locomotion wheelchair participants took disabilityfocused implicit association test two times experiencing ds also took test knowledge retention ms primary result experiencing ds locomotion wheelchair better disabilityrelated information recall task reducing implicit bias towards people use wheelchairspmid34310308 doi101109 tvcg20213099115,0.0
impact marriage physical activity behavior women multiple sclerosis disabil rehabil 2021 jul 2419 doi 101080 0963828820211953622 online ahead printabstractpurpose adopting continuing physical activity pa critical management multiple sclerosis ms role spouses partners play adoption continuation pa women ms yet exploredmethods nine women ms respective spouses volunteered indepth semistructured interviews lasted approximately hour interviews transcribed analyzed thematically spouse interview data used contextualize provide richer understanding themes women msresults three themes constructed analysis interview data women ms support motivation perform pa pa prior ms support discussed took form joining pa supporting pa accomplishments information sharing assisting pa encouraging separate pa motivation perform pa prior pa also impacted womens spouses behaviorsconclusions study points importance support perception support spouses women ms support highly valued regardless form took women ms benefit understanding encouraging various supporting roles spouses play decisions women ms make physically activeimplications rehabilitationwomen ms spouses consider physical activity beneficialwomen ms value support spouses provide encourage physically activewomen ms can perceive support spouses varying ways including support initiating physical activity supporting physical activity accomplishments information sharing assisting physical activity encouraging separate physical activityphysical activity programming population consider ways incorporate spousal supportpmid34308724 doi101080 0963828820211953622,0.0
detection structural conformational changes alscausing mutant profilin1 hydrogen deuterium exchange mass spectrometry bioinformatics techniques metab brain dis 2021 jul 24 doi 101007 s1101102100763y online ahead printabstractthe hydrogen deuterium exchange hdx reliable method survey dynamic behavior proteins epitope mapping matrixassisted laser desorption ionizationtime flight mass spectrometry malditof ms quantifying tool assay hdx protein interest combined hdxmalditof ms molecular docking md simulation identify accessible amino acids analyze contribution structural changes profilin1 pfn1 molecular docking md simulations computational tools enabling analysis type amino acids may involved via hdx identified lowest binding energy condition glycine valine amino acid g117v substitution mutation linked amyotrophic lateral sclerosis als mutation found actinbinding site pfn1 prevents dimerization polymerization actin invokes pathologic toxicity leads als study sought understand pfn1 protein dynamic behavior using purified wild type mutant pfn1 proteins data obtained hdxmalditof ms pfn1wt pfn1g117v various time intervals seconds hours revealed multiple peaks corresponding molecular weights monomers multimers pfn1 benzaldehyde complexes identified 20 accessible amino acids hdx participate docking simulation surface wt mutant pfn1 consistent results hdxmalditof ms docking simulation predict candidate amino acid s involved dimerization polymerization pfng117v information may shed critical light structural conformational changes details amino acid epitopes mutant pfn1s dimerization oligomerization aggregationpmid34302583 doi101007 s1101102100763y,0.0
id proteins emerging roles cns disease targets modifying neural stemcell behavior cell tissue res 2021 jul 24 doi 101007 s0044102103490z online ahead printabstractneural stem progenitor cells nspcs found adult brain spinal cord endogenous transplanted nspcs contribute repair processes regulate immune responses cns however molecular mechanisms nspc survival integration well fate determination functionality still poorly understood inhibitor dna binding id proteins increasingly recognized key determinants nspc fate specification id proteins act antagonizing dnabinding activity basic helixloophelix bhlh transcription factors balance id bhlh proteins determines cell fate decisions numerous cell types developmental stages id proteins central responses environmental changes occur cns injury disease cellular responses adult nspcs implicate id proteins prime candidates manipulating stemcell behavior outline recent advances understanding id protein pleiotropic functions cns diseases propose integrated view id proteins promise potential targets modifying stemcell behavior ameliorate cns diseasepmid34302526 doi101007 s0044102103490z,1.0
lived experience uncertainty everyday life ms disabil rehabil 2021 jul 2317 doi 101080 0963828820211955302 online ahead printabstractpurpose article examines issues control certainty uncertainty experienced managed everyday life multiple sclerosis ms explores ways people living ms make sense experiencesmaterials methods qualitative interviews 23 women men diagnosed ms four relatives carried denmark drawing notion phenomenological uncertainty thematic approach used analyse interview dataresults three themes characterise participants experience uncertainty body issues control symptom fluctuations disease progression understanding interpreting embodied ms experiences shared themes focus body multifaceted bodily aspects uncertainty across diverse temporalitiesconclusion phenomenological uncertainty shapes pervades everyday lived experience ms present future gaining sense control certainty face daily uncertainty demands ongoing selfsurveillance evaluation reconciliation fluctuating ms symptom expressions disease progression personal needs abilities management strategiesimplications rehabilitationrehabilitation professionals physicians consider lived experience uncertainty everyday life ms contacts people living msthe multifaceted uncertainties experienced people living ms actively acknowledged incorporated discussions ms rehabilitation options integrating ms guideline content activitiesofdailyliving advicediscussions ms medical treatment options actively consider integrate multifaceted uncertainties experienced people living mspmid34297648 doi101080 0963828820211955302,0.0
sensorymotor affectivefatigue factors associated symbol digit performance multiple sclerosis j int neuropsychol soc 2021 jul 2319 doi 101017 s1355617721000540 online ahead printabstractobjectives oral symbol digit modalities test sdmt become standard brief screening cognitive impairment persons multiple sclerosis pwms shown sensitive sensorymotor factors involving rudimentary oral motor speed visual acuity well multiple sclerosis ms affectivefatigue factors including depression fatigue anxiety present study designed provide greater understanding noncognitive factors might contribute oral sdmt examining variables samplemethods examined 50 pwms 49 healthy controls hcs participants administered oral sdmt two sensorymotor tasks visual acuity oral motor speed three affectivefatigue measures depression fatigue anxiety results partially consistent hypotheses found sensorymotor skills affectivefatigue factors accounted group differences ms hc groups oral sdmt reducing ms hc group variance predicted 10 4 also pwms average sensorymotor abilities oral sdmt scores lower pwms intact sensorymotor skills p 05 finally 71 pwms belowaverage sensorymotor group impaired oral sdmt compared 14 intact group p 006 conclusions oral sdmt used sole screening tool cognitive impairment ms clinicians know limitations visual acuity rudimentary oral motor speed considered possibly associated performance mspmid34294175 doi101017 s1355617721000540,0.0
optical coherence tomography associated cognitive impairment multiple sclerosis j neuroophthalmol 2021 jul 21 doi 101097 wno0000000000001326 online ahead printabstractbackground optical coherence tomography oct sensitive method quantifying retinal neuronal axonal structures reductions retinal nerve fiber layer rnfl ganglion cell inner plexiform layer gcipl thicknesses reported association white grey matter atrophy multiple sclerosis ms hypothesized thinning intraretinal layer measurements associates cognitive decline ms patients prior event optic neuritis methods oct neurotrax computerized cognitive assessments performed 204 relapsing remitting ms patients history conditions affecting eye data collected 2010 2020 retrospectively analyzed correlations examined cognitive performance lower rnfl gcipl thickness multilinear regression model generated assess significance correlations regarding disability score disease durationresults 204 study participants mean age 4052 118 years mean sd disease duration 980 940 years mean rnfl thickness whole cohort 8222 1085 m global cognitive score 9532 1232 mean gcipl thickness measured subgroup 104 patients 7427 1037 m rnfl gcipl correlated global cognitive score r 0174 p 0013 r 029 p 003 respectively various cognitive domains however gcipl showed stronger correlations rnfl particularly executive function r 029 p 0003 attention r 0332 p 0001 information processing speed r 025 p 0012 correlations remained significant correcting confoundersconclusion oct measurements correlate cognitive performance ms patients oct can thus used evaluate central nervous system neurodegeneration ms reflected cognitive declinepmid34294657 doi101097 wno0000000000001326,0.0
comparison study dimethyl itaconate dimethyl fumarate electrophilicity nrf2 activation antiinflammation vitro j asian nat prod res 2021 jul 22112 doi 101080 1028602020211949303 online ahead printabstractdimethyl itaconate dmi analog dimethyl fumarate dmf approved nfe2related factor 2 nrf2 activator multiple sclerosis study evaluated potential dmi antiinflammatory agent comparing dmi dmf electrophilicity nrf2 activation antiinflammation vitro results showed dmi less electrophilic better inducing durable activation nrf2 compared dmf however dmi demonstrated poor antiinflammatory effects jurkat cells bone marrowderived dendritic cells raw2647 cells study suggested dmi potent electrophilic nrf2 activator probably promising antiinflammatory agentpmid34292106 doi101080 1028602020211949303,0.0
risk multiple sclerosis relapses switching fingolimod celldepleting agents role washout duration j neurol 2021 jul 22 doi 101007 s00415021107081 online ahead printabstractbackground fingolimod fty induces sequestration lymphocytes secondary lymphoid organs average lymphocyte recovery following discontinuation takes 12 months hypothesized therapeutic effects subsequent celldepleting agents may compromised initiated lymphocyte recovery occurredobjective assess risk relapses following fty discontinuation initiation b t celldepleting agent relation washout duration using data italian ms registermethods risk relapses assessed relation different washout durations 6 611 1217 18 weeks patients starting alemtuzumab rituximab ocrelizumab cladribine following fty discontinuationresults included 329 patients analysis 226f 103 m mean age 41 10 years celldepleting treatment incidence rate ratio relapse significantly greater patients washout period 1217 18 weeks compared reference period 6 weeks risk relapse significantly influenced occurrence relapses fty treatment washout length hazard ratios markedly increasing washout durationconclusion risk relapses increases washout duration switching fty lymphocytedepleting agentspmid34292396 doi101007 s00415021107081,0.0
bcell depletion therapy multiple sclerosis immunol med 2021 jul 2119 doi 101080 2578582620211952543 online ahead printabstractsince initial observation increased immunoglobulin concentrations cerebrospinal fluid multiple sclerosis ms patients 1940s b cells considered participate pathology ms production autoantibodies reactive central nervous system antigens however now recognized b cells contribute ms relapses via antibodyindependent activities including presentation antigens t cells release proinflammatory cytokines addition recent identification b cellrich folliclelike structures meninges progressive ms patients suggests pathogenic roles b cells also exist progressive phase disease recently largescale clinical trials demonstrated efficacy bcell depletion therapy using anticd20 antibodies relapsing well primary progressive ms bcell depletion therapy become essential treatment option ms based unique benefit risk balance relapsing ms drug shown effective primary progressive ms datepmid34289331 doi101080 2578582620211952543,0.0
transcriptome analysis reveals key genes modulated alk5 inhibition bleomycin model systemic sclerosis rheumatology oxford 2021 jul 21keab580 doi 101093 rheumatology keab580 online ahead printabstractobjective systemic sclerosis ssc rheumatic autoimmune disease affecting roughly 20 000 people worldwide characterized excessive collagen accumulation skin internal organs despite high morbidity mortality associated ssc approved diseasemodifying agents objective study explore transcriptomic modelbased drug discovery approaches systemic sclerosismethods study explored molecular basis ssc pathogenesis wellstudied mouse model scleroderma profiled skin lung transcriptomes mice multiple timepoints analyzing differential gene expression underscores development resolution bleomycininduced fibrosisresults observed shared expression signatures upregulation downregulation fibrotic skin lung tissue observed significant upregulation key profibrotic genes including gdf15 saa3 cxcl10 spp1 timp1 identify changes gene expression responses antifibrotic therapy assessed effect tgf pathway inhibition via oral alk5 tgf receptor inhibitor sb525334 observed timelagged response lung relative skin also implemented machine learning algorithm showed promise predicting lung function using transcriptome data skin lung biopsiesconclusion study provides comprehensive look gene expression dynamics animal model systemic sclerosis date provides rich dataset future comparative fibrotic disease research helps refine understanding pathways work ssc pathogenesis interventionpmid34289031 doi101093 rheumatology keab580,0.0
identification quantification bu shen yi sui capsule uplcltqorbitrapmsn uplcqtofms ms j chromatogr sci 2021 jul 21bmab091 doi 101093 chromsci bmab091 online ahead printabstracttraditional chinese medicines tcms considered important alternative therapeutics significant medicinal benefits specific diseases chinese herb formula characterized vast molecule differs routine medicines due tcms chemical complexity proper quality control great challenge choosing appropriate method identify qualify compounds important work ensure safety efficacy quality control thus study aimed providing novel information highresolution ltqorbitrap mass spectrometer uplcltqorbitrapmsn based identification bu shen yi sui capsule bsysc used treating multiple sclerosis kind tcms proposed chromatographic conditions 80 chemical components classified anthraquinone phenolic acid phenylethanoid glycosides separated identified bsysc coupled highperformance liquid chromatography quadrupole timeofflight mass spectrometry uplcqtofms ms method eight regarded marker compounds quantitative evaluation bsysc identification quantification precision uplcltqorbitrapmsn uplcqtofms ms facilitate essential data pharmacokinetic studies bsyscpmid 34286839doi101093 chromsci bmab091,0.0
patient#39 s point view use telemedicine multiple sclerosis webbased survey neurol sci 2021 jul 20 doi 101007 s10072021053986 online ahead printabstractrestrictions access healthcare facilities covid19 pandemic raised need remote monitoring chronic medical conditions including multiple sclerosis ms order enable continuity care circumstances many telemedicine applications currently tested physicians preferences commonly investigated data regarding patients point view still lacking built 37 items webbased survey exploring patients propensity awareness opinions telemedicine aim evaluate sustainability approach ms analysing 613 questionnaires 1093 sent persons ms followed multiple sclerosis center tor vergata university rome found half respondents 54 open televisit propensity toward telemedicine significantly depended higher income p 0037 living farther center p 0038 using computer tablet p 0010 using internet remote activities p 0001 conversely influenced specific disease characteristics ie degree disability main advantages disadvantages televisit reported participants respectively saving time 70 impossibility measure physical parameters 71 although majority respondents favour televisit far approach restricted displaying better socioeconomic conditions higher familiarity technology implications study telemedicine platforms better tailored patients demands order spread use telemedicine enhance usability increase patients adherencepmid34283343 doi101007 s10072021053986,0.0
cannabis pain scoping review braz j anesthesiol 2021 jul 16s01040014 21 002748 doi 101016 jbjane202106018 online ahead printabstractfor centuries cannabis used many different purposes including medicinal use usually bypassing formal approval process however last decade interest cannabis medicine increasing several countries including united states canada produced legislation marihuana cannabisbased medicines interest research increasing evidence medical effects becoming necessary conducted review examining evidence cannabis pain cannabis shown useful acute chronic pain however recently results controverted within different types chronic pain weak evidence neuropathic rheumatic pain headache modest evidence multiple sclerosis related pain adjuvant therapy cancer pain strong evidence recommend cannabis order decrease opioids patients chronic use even though cannabisbased medications appear mostly safe mild adverse effects common somnolence sedation amnesia euphoric mood hyperhidrosis paranoia confusion may limit use cannabis clinical practice risks systematically analyzed special concern arises adverse effect might affect vulnerable population elderly patients research needed order evaluate benefits risks well ideal administration route dosages cannabis use increases several countries answers questions might coming soonpmid34280454 doi101016 jbjane202106018,0.0
neurite orientation dispersion density imaging discloses early changes normalappearing white matter paediatric multiple sclerosis j neurol neurosurg psychiatry 2021 jul 16jnnp2021326355 doi 101136 jnnp2021326355 online ahead printno abstractpmid34272345 doi101136 jnnp2021326355,0.0
ensemble learning multiple sclerosis disability estimation using brain structural connectivity brain connect 2021 jul 16 doi 101089 brain20201003 online ahead printabstractbackground multiple sclerosis ms autoimmune inflammatory disease central nervous system characterized demyelination neurodegeneration processes leads different clinical courses degrees disability need anticipated neurologist personalized therapy recently machine learning ml techniques reached high level performance brain disease diagnosis prognosis decision process trained ml system typically nontransparent using brain structural connectivity data fully automatic ensemble learning model augmented interpretable model proposed estimation ms patients disability measured expanded disability status scale edss method ensemble four boostingbased models gbm xgboost catboost lightboost organized following stacking generalization scheme developed using dtibased structural connectivity data addition interpretable model based conditional logistic regression developed explain best performances terms white matter wm links three classes edss low medium high results ensemble model reached excellent level performance rmse 092 028 compared singlebased models provided better edss estimation using dtibased structural connectivity data compared conventional mri measures associated patient data age gender disease duration used interpretation estimation process counterfactual method showed importance certain brain networks corresponding mainly left hemisphere wm links connecting left superior temporal left posterior cingulate right precuneus gray matter regions interhemispheric wm links constituting corpus callosum also better accuracy estimation found high disability classconclusion combination advanced ml models sensitive techniques dtibased structural connectivity demonstrated useful estimation ms patients disability point important brain wm networks involved disabilitypmid34269618 doi101089 brain20201003,1.0
association acute zonal occult outer retinopathy multiple sclerosis report 2 cases j neuroophthalmol 2021 jul 13 doi 101097 wno0000000000001283 online ahead printno abstractpmid34270517 doi101097 wno0000000000001283,0.0
investigating job satisfaction palliative rehabilitation reflections perspectives health professionals working amyotrophic lateral sclerosis j eval clin pract 2021 jul 16 doi 101111 jep13599 online ahead printabstractstudy rationale amyotrophic lateral sclerosis progressive neurodegenerative disease causes impairment motor functions upper lower limbs bulbar muscles median survival time three years first appearance symptoms massive psychological impact health professionals persons amyotrophic lateral sclerosis hence work leads multiple challenges stressful demanding situations high risk experiencing diminished personal wellbeing including burnout moral distress compassion fatigueaim investigate reflections perspectives health professionals working within palliative rehabilitation elements importance relation job satisfactionmethods materials design qualitative based phenomenologicalhermeneutical methodology paul ricoeurs interpretation theory data consisted two semistructured focus group interviews total 12 specialized health professionals nurses psychologists physicians occupational therapists physiotherapists social workers working within hospital setting specialized palliative rehabilitation people amyotrophic lateral sclerosis familiesresults analysis revealed insight four themes fundamental drive working conditions value collegiality worklife balance fundamental drive deeply rooted professionals sense meaningful job working conditions selfmanagement important job satisfaction good collegial relations finally good balance working life private life considered important job satisfactionconclusion study indicates work within field palliative rehabilitation experienced enriching beneficial right circumstances appreciatory working environment found elements like autonomy mastery purpose collegiality worklife balance great importance findings can help guide managements health professionals palliative rehabilitation contexts ensure satisfied employees optimize quality carepmid34269500 doi101111 jep13599,0.0
dymus dypark validation screening questionnaire dysphagia parkinson#39 s disease dysphagia 2021 jul 15 doi 101007 s00455021103321 online ahead printabstractdysphagia common debilitating symptom people parkinsons disease pd adequate screening swallowing disorders fundamental dymus questionnaire shown good characteristics screening dysphagia multiple sclerosis might also prove useful screening dysphagia pd primary aim test validate dymus questionnaire pd patients observational multicentric study involving 103 patients affected pd subjects filled dymus eating assessment tool eat10 questionnaires subgroup patients n 53 underwent fiberoptic endoscopic evaluation swallowing fees dysphagia scored means dysphagia outcome severity scale doss dymus showed relatively high level internal consistency cronbachs alpha 079 significant positive correlation found dymus eat10 scores p 0001 negative correlation found dymus doss scores p 0001 dymus showed good sensitivity specificity compared fees detecting dysphagia area curve 082 p 0001 roc curve analysis showed dymus score 6 represents reliable cutoff risk dysphagia dymus questionnaire proved reliable screening tool detect dysphagia patients suffering pd easy understand can selfadministered therefore adequate adoption clinical practice convenient name dyparkpmid34264379 doi101007 s00455021103321,0.0
safety alemtuzumab nationwide cohort finnish multiple sclerosis patients j neurol 2021 jul 13 doi 101007 s0041502110664w online ahead printabstractbackground alemtuzumab effective diseasemodifying therapy dmt highly active multiple sclerosis ms however safety concerns limit use clinical practiceobjectives evaluate safety alemtuzumab nationwide cohort finnish ms patientsmethods retrospective case series study analyzed data two ms patients received alemtuzumab finland 2019 data systematically collected patient filesresults altogether 121 patients identified received previous dmts 826 median followup time treatment initiation 303 months exceeded 24 months 78 patients infusionassociated reactions iars observed 843 573 571 patients alemtuzumab courses 13 respectively serious adverse events saes observed 322 patients serious iars 124 patients saes iars 231 patients autoimmune adverse events observed 306 patients one patient died hemophagocytic lymphohistiocytosis one patient died pneumonia previously unreported case thrombotic thrombocytopenic purpura documentedconclusions saes frequent present cohort previous studies even though alemtuzumab highly effective therapy ms vigorous monitoring long enough followup time advisedpmid34255182 doi101007 s0041502110664w,0.0
understanding visualspatial perceptual deficits individuals multiple sclerosis analysis patient performance hooper visual organization test visual form discrimination int j neurosci 2021 jul 1319 doi 101080 0020745420211954642 online ahead printabstractalthough cognitive sequelae multiple sclerosis recognized four decades focus research studying common deficits disease including involving memory information processing speed less understood investigated visualspatial perceptual disturbances multiple sclerosis can difficult assess interpret given potential confounds associated physical problems cognitive disturbances disorder study examined visualspatial perceptual deficits multiple sclerosis 40 participants diagnosed condition using two measures generally unaffected aforementioned confounds hooper visual organization test visual form discrimination results revealed measures sensitive impairments multiple sclerosis suggested assessing somewhat different aspects visualspatial perception population given relationship one another diseaserelated variables light findings indicate complete accurate understanding visualspatial perceptual sequelae multiple sclerosis requires administration single measurepmid34253124 doi101080 0020745420211954642,0.0
cognitive rehabilitation program patients multiple sclerosis pilot study neurologia 2021 jul 9s02134853 21 000888 doi 101016 jnrl202103014 online ahead printabstractintroduction recent years increase studies dedicated cognitive rehabilitation patients multiple sclerosis ms however analyze impact variables cognitive reserve study aims explore effects cognitive rehabilitation program comprising combination cognitive physical exercises well group sessions improve cognitive performance emotional state cognitive reserve indexmethod fifty patients ms subdivided 2 groups control group performed aerobic exercise n25 experimental group n25 participated integrated cognitive rehabilitation program icrp participants evaluated 3 times baseline posttreatment longterm brief repeatable battery neuropsychological tests cognitive reserve scale beck depression inventory scale evaluating trait state anxietyresults compared control group patients experimental group showed improvements cognitive function significant changes measures information processing speed attention memory cognitive reserve index longterm moodconclusions icrp effective improving cognitive emotional function ms increased cognitive reserve indexpmid34253414 doi101016 jnrl202103014,0.0
review neurological rehabilitation multiple sclerosis british military bmj mil health 2021 jul 12bmjmilitary2021001852 doi 101136 bmjmilitary2021001852 online ahead printabstractmultiple sclerosis ms progressive neurological disorder classically presenting working age adults including armed forces defence medical rehabilitation centre dmrc stanford hall offers vocationally focused neurorehabilitation services service personnel sp ms goal minimise disability maximise independence remain able workthis paper two aims first briefly provides clinical update ms focusing pathology presentation diagnosis management finally will describe role dmrc data last decade management msour findings suggest sp ms referred dmrc significant delays potentially impacting patient support symptom management occupational outcomes hoped paper will improve awareness recognition ms armed forces personnelpmid34253640 doi101136 bmjmilitary2021001852,1.0
pleiotrophin serum level increased relapsingremitting multiple sclerosis correlates sex bmi treatment arch med res 2021 jul 9s01884409 21 001405 doi 101016 jarcmed202106005 online ahead printabstractbackground multiple sclerosis ms immunemediated demyelinating disease mainly affecting central nervous system cns 80 ms patients present relapsingremitting form rrms pleiotrophin ptn cytokine previously associated autoimmune neurological diseases play role pathophysiology rrms due neuro immunomodulatory effect however ptn never explored rrms patientsaim study determine ptn serum levels patients rrms treated glatiramer acetate ga interferonbeta ifn well nontreated patients healthy controls first attempt explore ptn rrmsmethods ptn serum levels quantified elisa 57 patients 18 controlsresults demonstrated ptn serum levels significantly higher rrms patients ifn treated patients alone ptn correlated positively time disease evolution time ifn use correlated negatively ms severity score msss comparing groups according weight status observed ptn statistically increased overweight female patients weight affect male patients area curve auc receiver operating characteristic roc curve analysis higher males compared femalesconclusion ptn serum level higher rrms patients associated sex bmi ifn treatment therefore propose ptn playing role ms studies must performed identify exact role ptn pathologypmid34247888 doi101016 jarcmed202106005,1.0
tspo imaging animal models brain diseases eur j nucl med mol imaging 2021 jul 10 doi 101007 s0025902105379z online ahead printabstractover last 30 years 18kda tspo protein considered pet imaging biomarker reference measure increased neuroinflammation generally assumed image activated microglia tspo also detected endothelial cells activated astrocytes provide exhaustive overview recent literature tspopet imaging search development new tspo tracers ii understanding acute chronic neuroinflammation animal models neurological disorders generally studies testing new tspo radiotracers prototypic 11c rpk11195 recent competitors use models acute focal neuroinflammation eg stroke lipopolysaccharide injection studies led development 60 new tracers last 15 years studies highlighted interpretation tspopet easier acute models focal lesions whereas chronic models lower diffuse microglial activation models alzheimers disease parkinsons disease tspo quantification detection neuroinflammation challenging mirroring observed clinic moreover technical limitations preclinical scanners provide drawback studying modest neuroinflammation small brains eg mice overall review underlines value tspo imaging study time course response treatment neuroinflammation acute chronic models diseases tspo remains gold standard biomarker reference neuroinflammation waiting new radioligands specific targets neuroinflammatory processes immune cells emergepmid34245328 doi101007 s0025902105379z,0.0
fingolimod significantly reduces mri activity paediatriconset multiple sclerosis ms arch dis child educ pract ed 2021 jul 9edpract2021322317 doi 101136 archdischild2021322317 online ahead printno abstractpmid34244234 doi101136 archdischild2021322317,0.0
corneal parameters patients multiple sclerosis pilot study klin monbl augenheilkd 2021 jul 9 doi 101055 a14972238 online ahead printabstractobjective evaluate corneal topographic parameter values measured pentacam scheimpflug system patients multiple sclerosis ms methods total 108 eyes 62 ms patients studied addition complete examination anterior posterior segments patients scanned using pentacam scheimpflug camera diagnosis ms made according mcdonald criteria ms patients clinically assessed using multiple sclerosis severity score msss results mean age 3889 1018 years 3616 4130 ms patients 4094 944 years 3849 4311 controls p 026 central corneal thickness cct corneal volume cv values significantly lower ms patients p 0001 corneal parameters significantly different study eyes control eyes p 005 pachymetric measurements corneal apex 52569 2935 51829 53367 m study eyes versus 56313 2370 56213 57636 m control eyes cv 5922 411 5818 6020 mm3 study eyes versus 6278 309 6238 6400 mm3 control eyesconclusion first study reported lower cct cv measurements ms patients healthy subjects similar age results supported studiespmid34243216 doi101055 a14972238,0.0
modulation mitochondrial inflammatory homeostasis rip140 neuroprotective adrenoleukodystrophy mouse model neuropathol appl neurobiol 2021 jul 8 doi 101111 nan12747 online ahead printabstractaims mitochondrial dysfunction inflammation core axonal degeneration several multifactorial neurodegenerative diseases including multiple sclerosis alzheimers parkinsons disease transcriptional coregulator rip140 nrip1 receptorinteracting protein 140 modulates functions liver adipose tissue role nervous system remains unexplored investigated impact rip140 abcd1 mouse model xlinked adrenoleukodystrophy xald genetic model chronic axonopathy involving convergence redox imbalance bioenergetic failure chronic inflammationmethods results provide evidence rip140 modulated redoxdependent mechanism driven longchain fatty acids vlcfas levels increased xald genetic inactivation rip140 prevented mitochondrial depletion dysfunction bioenergetic failure inflammatory dysregulation axonal degeneration associated locomotor disabilities vivo xald mouse modelsconclusions together findings show aberrant overactivation rip140 promotes neurodegeneration xald underscoring potential therapeutic target xald neurodegenerative disorders present metabolic inflammatory dyshomeostasispmid34237158 doi101111 nan12747,1.0
diagnosis management multiple sclerosis relapsing demyelinating disease childhood arch dis child 2021 jul 6archdischild2021321911 doi 101136 archdischild2021321911 online ahead printabstractthere several important relapsing demyelinating syndromes rds may present childhood paediatriconset multiple sclerosis common rare conditions recognising presentations referring early specialist services important enable prompt diagnosis effective treatment understanding rds rapidly evolving many new effective treatments aim reduce relapses disability accumulation holistic childfocused approach management key supporting patients families thought given early detection cognitive psychological issues provide appropriate supportpmid34230009 doi101136 archdischild2021321911,1.0
depression multiple sclerosis mediate effects cognitive functioning quality life qual life res 2021 jul 6 doi 101007 s1113602102927w online ahead printabstractpurpose patients multiple sclerosis ms significant risk decreased quality life qol part due factors cognitive impairment depression however objective versus subjective assessments cognitive functioning may differentially predict qol remains unknown whether impact qol levels depression aims present study included 1 testing effects cognitive impairment msrelated qol via depression symptoms 2 examining whether perceived objective cognitive functioning differentially predict qol depressionmethods patients formally diagnosed ms n 128 participated cognitive assessment brief international cognitive assessment multiple sclerosis completed selfreport measures perceived cognitive functioning perceived deficits questionnaire depression hospital anxiety depression scale msrelated qol functional assessment multiple sclerosis results mediational hypotheses tested regression structural equation modeling hypothesized perceived objective cognitive functioning independently predicted lower qol controlling effects depression p 0001 consistent hypotheses depression mediated effects perceived 95 ci 031 068 objective cognitive functioning 95 ci 009 696 qol tested separate models however predictors modeled simultaneously depression mediated effects perceived objective cognitive functioning 95 ci standardized effect 010 061 conclusions study thus suggests need conceptualize different pathways objective subjective cognitive impairment may shape qol lives individuals mspmid34228241 doi101007 s1113602102927w,0.0
autoimmune neurogenic dysphagia dysphagia 2021 jul 5 doi 101007 s00455021103389 online ahead printabstractautoimmune neurogenic dysphagia refers manifestation dysphagia due autoimmune diseases affecting muscle neuromuscular junction nerves roots brainstem cortex dysphagia either part evolving clinical symptomatology underlying neurological autoimmunity occurs sole manifestation acutely insidiously opinion article reviews autoimmune neurological causes dysphagia highlights clinical clues laboratory testing facilitate early diagnosis especially dysphagia presenting symptom outlines effective immunotherapeutic approaches dysphagia common inflammatory myopathies prominently inclusion body myositis frequent myasthenia gravis occurring early bulbaronset disease course progressive generalized disease acuteonset dysphagia often seen guillainbarre syndrome variants slowly progressive dysphagia paraneoplastic neuropathies highlighted presence specific autoantibodies common causes cns autoimmune dysphagia demyelinating inflammatory lesions brainstem occurring patients multiple sclerosis neuromyelitis optica spectrum disorders less common often overlooked dysphagia stiffperson syndrome especially conjunction cerebellar ataxia high antigad autoantibodies gastrointestinal dysmotility syndromes associated autoantibodies ganglionic acetylcholine receptor setting many neurological autoimmunities acuteonset progressive dysphagia potentially treatable condition requiring increased awareness prompt diagnosis early immunotherapy initiationpmid34226958 doi101007 s00455021103389,1.0
vibration therapy role neurological diseases rehabilitation umbrella review systematic reviews disabil rehabil 2021 jul 519 doi 101080 0963828820211946175 online ahead printabstractpurpose summarize findings evaluate role vibratory therapy rehabilitation neurological diseasesmethods systematically research pubmed scopus embase physiotherapy evidence database pedro web science cochrane library databases inception november 2020 included studies compared wholebody vibration wbv focal muscle vibration fmv placebo sham another form exercise neurological disease rehabilitation children adults result motor impairments disabilityresults included 16 systematic reviews good methodological quality evaluated using joanna briggs institute umbrella review assessment review information appraisal tool stroke patients wbv appears play role improving gait balance fmv effective reducing spasticity multiple sclerosis cerebral palsy evidence suggested vibration therapy increases patient outcomesconclusion wbv fmv appear play considerable role reducing spasticity improving gait balance motor function stroke patients contrast vibration therapy seems unable reduce spasticity multiple sclerosis cerebral palsy also correct use parameters therapy definedimplications rehabilitationbased growing number systematic reviews umbrella review aimed summarize findings evaluate role vibration therapy rehabilitation neurological diseaseswholebody vibration focal muscle vibration appear play considerable role reducing spasticity improving gait balance motor function patients affected strokefocal muscle vibration appears useful applied nonspastic antagonist muscles reciprocal inhibitory action spastic muscles subjects affected strokevibration therapy seems able reduce spasticity multiple sclerosis cerebral palsypmid34225557 doi101080 0963828820211946175,0.0
novel drug delivery system curcumin implementation improve therapeutic efficacy neurological disorders comb chem high throughput screen 2021 jul 4 doi 102174 1386207324666210705114058 online ahead printabstractbackground curcumin hydrophobic polyphenolic compound present curcuma longa linn turmeric used improve various neurodegenerative conditions including amyotrophic lateral sclerosis multiple sclerosis parkinsons disease prion disease stroke anxiety depression ageing however bloodbrain barrier bbb impedes delivery curcumin brain result limits therapeutic potentialobjective aim review summarises recent advances towards therapeutic efficacy curcumin along various novel strategies overcome poor bioavailability across bloodbrain barriermethods collection data compilation review work searched pubmed scopus google scholar science directresult various approaches opted expedite delivery curcumin across bloodbrain barrier including liposomes micelles polymeric nanoparticles exosomes dual targeting nanoparticles etc conclusion review also summarises numerous toxicological studies role curcumin cns disorderspmid34225614 doi102174 1386207324666210705114058,1.0
bruch membrane opening minimum rim width neuromyelitis optica j neuroophthalmol 2021 jul 1 doi 101097 wno0000000000001297 online ahead printabstractbackground optical coherence tomography oct analyzes neurodegeneration neuromyelitis optica nmo multiple sclerosis ms quantifies optical atrophy retinal nerve fiber layer rnfl ganglion cell layer gcl thickness decreased structural change correlated visual function patients including contrast vision visual field deviation main objective study evaluate bruch membrane opening minimum rim width bmo patients nmomethods studied thickness bmo oct patients nmo n 25 34 eyes ms n 50 70 eyes control group n 51 100 eyes study evaluated structurefunction relationship correlation oct visual function visual acuity pellirobson score sloan 25 125 color vision standard automated perimetry sap frequencydoubling technology perimetry fdt results average thickness bmo significantly reduced nmo ms without history optic neuritis significant thinning average nasal inferonasal bmo absence nmo found compared controls p 0022 0006 0026 respectively bmo strongly correlated pellirobson score p 0001 sloan 25 p 0001 mean deviation sap fdt p 0004 sectorial study found high correlation bmo corresponding sector visual fieldconclusions bmo thickness decreased nmo ms study showed improved ability bmo rnfl gcl detect infraclinical impairment patients nmo without history optic neuropathy like rnfl gcl bmo well correlated visual function including contrast vision visual field deviationpmid34224526 doi101097 wno0000000000001297,0.0
novel role nogo proteins regulating macrophages inflammatory disease cell mol neurobiol 2021 jul 5 doi 101007 s10571021011240 online ahead printabstractnogo proteins also known reticulon4 identified myelinderived inhibitors neurite outgrowth central nervous system cns three nogo variants nogoa nogob nogoc recent studies shown nogoa b abundant macrophages may wider effect inflammation review focus mainly possible roles nogoa b polarization recruitment macrophages involvement variety inflammatory diseases discuss nogo receptor1 ngr1 common receptor nogo proteins also abundant microglia macrophage cns interaction nogo ngr1 microglia macrophage may affect adhesion polarization macrophages involved multiple neurodegenerative diseases including alzheimers disease multiple sclerosis overall review provides insights roles nogo proteins regulating macrophage functions suggests potentially nogo proteins maybe new target treatment inflammatory diseasespmid34224050 doi101007 s10571021011240,1.0
optic neuritis classification 2021 eur j ophthalmol 2021 jul 311206721211028050 doi 101177 11206721211028050 online ahead printabstractoptic neuritis can associated inflammatory disease central nervous system can isolated without relapse can also associated infectious systemic disease multiple associations based variety clinical radiological biological criteria changed time led overlapping phenotypes single case can classified several ways simultaneously time early intensive treatment often required diagnosis rapid precise review present current state knowledge diagnostic criteria aetiologies adults children discuss overlapping phenotypes propose homogeneous classification scheme even distinctions typical atypical relevant phenotypes largely overlapping clinical criteria neither sensitive enough specific enough assure diagnosis initial cases clinicians perform contrast enhanced mri brain orbits cerebral spinal fluid analysis biological analyses exclude secondary infectious inflammatory systematic screening mogigg aqp4igg igg recommended children still matter debate adults early recognition neuromyelitis optica spectrum disorder mogiggassociated disorder chronic relapsing idiopathic optic neuritis required diagnoses require therapies relapse prevention different used treat multiple sclerosispmid34218696 doi101177 11206721211028050,0.0
bruton#39 s tyrosine kinase inhibition treatment preclinical models multiple sclerosis curr pharm des 2021 jul 1 doi 102174 1381612827666210701152934 online ahead printabstractsignificant progress made understanding immunopathogenesis multiple sclerosis ms recent years successful clinical trials cd20depleting monoclonal antibodies corroborated fundamental role b cells pathogenesis ms reinforced notion cells b cell lineage attractive treatment target therapeutic inhibition brutons tyrosine kinase btk enzyme involved b cell myeloid cell activation function regarded nextgeneration approach aims attenuate errant innate adaptive immune functions moreover brainpenetrant btk inhibitors may impact compartmentalized inflammation neurodegeneration within central nervous system targeting brainresident b cells microglia respectively preclinical studies animal models ms corroborated impact btk inhibition meningeal inflammation cortical demyelination notably btk inhibition attenuated antigenpresenting capacity b cells generation encephalitogenic t cells evobrutinib selective oral btk inhibitor tested recently phase 2 study patients relapsingremitting ms study met primary endpoint significantly reduced cumulative number gadoliniumenhancing lesions treatment evobrutinib compared placebo treatment thus results ongoing phase 2 3 studies evobrutinib fenobrutinib tolebrutinib relapsingremitting progressive ms eagerly awaited review article introduces physiological role btk summarizes preclinical trial evidence addresses potential beneficial effects btk inhibition mspmid34218776 doi102174 1381612827666210701152934,1.0
leg movement activity sleep multiple sclerosis without rls j clin sleep med 2021 jun 24 doi 105664 jcsm9466 online ahead printabstractstudy objectives carry analysis leg movement activity sleep polysomnography psg dataset patients multiple sclerosis ms comparison idiopathic restless legs syndrome irls healthy controlsmethods crosssectional observational instrumental study fiftyseven patients males females 11 46 mean age 462102 years diagnosis ms underwent telephone interview assessing five standard diagnostic criteria rls psg sleep architecture leg movement activity lma sleep subsequently compared 1 40 ms patients without rls msrls vs 28 healthy controls 2 17 ms patients rls ms+rls vs 35 patients irls 3 ms+rls vs msrlsresults msrls ms+rls presented increased sleep latency percentage sleep stage n1 reduced total sleep time compared healthy controls irls respectively periodic limb movements sleep plms index plmsi higher msrls healthy controls p 0035 lower ms+rls compared irls p 0024 plms ms+rls less periodic less often bilateral shorter single movements compared typical plms irlsconclusions ms risk factor rls plms lower sleep quality comparison healthy patients plms ms+rls fewer shorter compared irls results suggest dissociation motor plms sensory symptoms rls sensory component rls secondary ms possible treatment implicationspmid34216201 doi105664 jcsm9466,0.0
clinical features maxillary sinus fungus ball patients malignant hematological disease eur arch otorhinolaryngol 2021 jul 3 doi 101007 s00405021069735 online ahead printabstractpurpose previous studies fungus balls primarily focused immunocompetent patients studies described clinical characteristics fungus balls malignant hematological disease mhd patients therefore compared clinical features maxillary sinus fungus ball msfb immunosuppressive patients mhd immunocompetent patientsmethods twenty patients mhd 40 randomly selected immunocompetent patients enrolled divided mhd nonmhd groups patients diagnosed msfb clinical features retrospectively analyzedresults patients mhd group nonspecific clinical symptoms endoscopic manifestations msfb similar nonmhd group computed tomography ct mhd group showed higher lundmackay scores lesser single sinus opacifications multiple sinus opacifications affected side bilateral opacifications compared nonmhd group mhd group lower frequency central hyperdensity heterogeneous opacifications nonmhd group significant differences two groups terms fungalinfected side lateral sinus wall ratio sclerosis lateral sinus wall erosion inner sinus wall nasal septum deviationconclusion clinical symptoms endoscopic manifestations msfb patients mhd similar immunocompetent patients however atypical signs wider mucosal inflammation found ct scans msfb patients mhd results indicate caution executed excluding possibility fungus balls immunosuppressive patientspmid34216265 doi101007 s00405021069735,0.0
nmosd ms prevalence indigenous populations australia new zealand j neurol 2021 jul 2 doi 101007 s00415021106659 online ahead printabstractbackground studied prevalence neuromyelitis optica spectrum disorder nmosd multiple sclerosis ms indigenous populations australia new zealand aim assessing potential differencesmethods cases possible nmosd ms collected australia new zealand clinical details mr imaging serologic results used apply 2015 ipnd diagnostic criteria nmosd 2010 mcdonald criteria ms frequencies selfdetermined ethnic ancestry calculated confirmed nmosd suspected nmosd ms prevalence rates nmosd ms according ancestry comparedresults 75 cases nmosd 89 suspected nmsod 101 ms nmosd cases likely asian indigenous ancestry compared suspected nmosd ms differences clinical phenotype nmosd seen indigenous compared european ancestry populations per 100 000 prevalence estimate nmosd people mori ancestry 150 95 ci 052249 similar asian ancestry 157 95 ci 115198 nmosd prevalence australian aboriginal torres strait islander populations 038 95 ci 000080 per 100 000conclusion prevalence nmosd mori population similar south east asian countries reflecting historical origins prevalence ms group intermediate south east asian european ancestry living new zealand nmosd particularly ms appear uncommon indigenous populations australiapmid34213614 doi101007 s00415021106659,0.0
microstructureweighted connectomics multiple sclerosis brain connect 2021 jul 1 doi 101089 brain20210047 online ahead printabstractintroduction graph theory applied study pathophysiology multiple sclerosis ms since provides global focal measures brain networks properties affected ms typically connections strength consequently network s properties computed counting number streamlines nos connecting couples grey matter regions however recent studies shown method quantitativemethods evaluated diffusionbased microstructural measures extracted three different models assess network properties group sixtysix ms patients sixtyfour healthy subjects besides assessed correlation patients disability biological measure neuroaxonal damageresults graph metrics extracted connectomes weighted intraaxonal microstructural components sensitive ms pathology related clinical disability hand measures network segregation extracted connectomes weighted maps describing extracellular diffusivity related serum concentration neurofilament light chain network properties assessed nos neither sensitive ms pathology correlated clinical pathological measures disease impact ms patientsconclusion using tractometryderived graph measures ms patients identified set metrics based microstructural components highly sensitive disease provide sensitive correlates clinical biological deterioration ms patientspmid34210167 doi101089 brain20210047,0.0
reversal behavioural phenotype cannabinoidlike compound vsn16r fragile x syndrome mice brain 2021 jul 1awab246 doi 101093 brain awab246 online ahead printabstractfragile x syndrome common inherited intellectual disability monogenetic cause autism spectrum disorder neurodevelopmental condition occurring due cgg trinucleotide expansion fmr1 gene polymorphisms variants largeconductance calciumactivated potassium channels increasingly linked intellectual disability loss fmr protein caused reduced largeconductance calciumactivated potassium channel activity leading abnormalities synapse function using cannabinoidlike largeconductance calciumactivated potassium channel activator vsn16r rescued behavioural deficits repetitive behaviour hippocampal dependent tests daily living hyperactivity memory mouse model fragile x syndrome vsn16r shown safe phase 1 study healthy volunteers phase 2 study people multiple sclerosis high oral bioavailability serious adverse effects reported vsn16r therefore directly utilised fragile x syndrome clinical study moreover vsn16r showed evidence tolerance strongly suggests chronic vsn16r may great therapeutic value fragile x syndrome autism spectrum disorder study provides new insight pathophysiology fragile x syndrome identifies new pathway drug intervention debilitating disorderpmid34196695 doi101093 brain awab246,0.0
role gut microbiota multiple sclerosis potential therapeutic implications curr neuropharmacol 2021 jun 29 doi 102174 1570159x19666210629145351 online ahead printabstractthe role gut microbiota health diseases receiving increased attention recently emerging evidence previous studies gutmicrobiotabrain axis highlighted importance gut microbiota neurological disorders multiple sclerosis ms chronic inflammatory demyelinating disease central nervous system cns resulting tcelldriven myelindirected autoimmunity dysbiosis gut microbiota ms patients reported published research studies indicating gut microbiota plays important role pathogenesis ms gut microbiota also reported influence initiation disease severity experimental autoimmune encephalomyelitis animal model ms however underlying mechanisms gut microbiota involvement pathogenesis ms remain unclear therefore review summerized potential mechanisms gut microbiota involvement pathogenesis ms including increasing permeability intestinal barrier initiating autoimmune response disrupting bloodbrain barrier integrity contributing chronic inflammation possibility gut microbiota target ms therapy also discussed review provides new insight understanding role gut microbiota neurological inflammatory diseasespmid34191698 doi102174 1570159x19666210629145351,1.0
serological response sarscov2 vaccination multiple sclerosis patients treated fingolimod ocrelizumab initial reallife experience j neurol 2021 jun 26 doi 101007 s0041502110663x online ahead printabstractbackground recent observations suggest lack humoral response sarscov2 vaccination multiple sclerosis ms patients treated fingolimod ocrelizumab objectives assess serological response sarscov2 vaccination ms patients receiving diseasemodifying treatments dmts reallife settingmethods retrospective clinical data collection ms patients followed san raffaele hospital ms centre milan italy patients treated fingolimod ocrelizumab received complete anticovid19 vaccination course clinical history suggestive previous sarscov2 infection available postvaccination serological assay obtained least 14 days vaccination completion considered studyresults collected data 32 ms patients 16 treated fingolimod 16 receiving ocrelizumab among fingolimod group 10 patients 625 positive serological response vaccination among ocrelizumabtreated patients positive serological test found six cases 375 relation serological response clinical features ie treatment duration time vaccination last treatment dose white blood cells count identifiedconclusions initial reallife experience suggests variable antibody production ms patients receiving dmts present sufficient data recommend antisarscov2 vaccine patientspmid34189719 doi101007 s0041502110663x,1.0
pml risk main factor driving choice discontinuing natalizumab large multiple sclerosis population results italian multicenter retrospective study j neurol 2021 jun 28 doi 101007 s00415021106766 online ahead printabstractbackground natalizumab ntz effective treatment relapsingremitting multiple sclerosis rrms however patients physicians may consider discontinuing ntz therapy due safety efficacy issues aim study evaluate ntz discontinuation rate reasons discontinuation large italian population rrms patientsmaterials methods data extracted italian ms registry may 2018 collected 51 845 patients 69 italian multiple sclerosis centers ms patients least one ntz infusion period june 1st 2012 may 15th 2018 included discontinuation rates time point calculated reasons ntz discontinuation classified lack efficacy progressive multifocal leukoencephalopathy pml risk otherresults 51 845 5151 patients 3019 586 females mean age 436 101 years median 40 analyzed 2037 395 discontinued ntz significantly higher percentage suspended ntz pml risk compared lack efficacy 1682 327 5151 vs 221 43 p 0001 reasons identified 99 19 patients patients discontinuing treatment older longer disease duration worse edss time ntz initiation last followup ntz treatment jcv index edss baseline predictors stopping therapy hr 294 95 ci 122475 p 002 hr 136 95 ci 118541 p 004 conclusions roughly 60 ms patients stayed ntz treatment observation period patients ntz discontinuation required mainly due pml concernspmid34181077 doi101007 s00415021106766,0.0
improved assessment overall health variably aged murine models multiple sclerosis novel frailty index tool j gerontol biol sci med sci 2021 jun 28glab185 doi 101093 gerona glab185 online ahead printabstractthe experimental autoimmune encephalomyelitis eae model commonly used animal model multiple sclerosis ms however phenotypic characterization mice based traditional 5point clinical paralysis scale fully capture disease progression frailty index fi conceptualizes frailty accumulation health deficits widely used assess overall health aging humans preclinical models adapted established mouse fi tool use eae mice determined whether evaluate general signs health variably aged female eae mice eaeclinical fi included 34 items related clinical signs deficits characteristic aging ms tool clearly showed detailed eae progression severity ages highlighting changes systems motor paralysis measured traditional 5point paralysis scale induced disease 3 6monthsofage mice showed typical eae clinical manifestations peak disease severity 1719 days postinduction mean frailty scores 036 004 3monthold 043 005 6monthold contrast disease severity peaked 14 days 12monthold mice showed atypical signs including wobbling early belly drag splayed hindlegs better captured eaeclinical fi peak frailty scores also higher younger animals 054 004 ms often develops young middleaged people new tool may significant value use eae animal studies first step towards translation people mspmid34181005 doi101093 gerona glab185,0.0
therapeutic plasma exchange neurological diseases eleven years experience tertiary care center turkey ther apher dial 2021 jun 26 doi 101111 1744998713703 online ahead printabstractobjective therapeutic plasma exchange tpe apheresis procedure plasma separated blood cellular components ex vivo allocated replaced another plasma plasmareplacing fluid study aimed define rate complications determine tpe distribution various neurological diseasesmaterials methods study retrospective analysis neurologic diseases requiring tpe 2008 2019 selected using medical records neurology departments apheresis units databaseresults performed 1459 tpe procedures 207 patients 2008 2019 tpe procedure frequently applied patients myastheniagravis syndrome 347 complication ratio 16 total 1459 tpe procedures commonly specified adverse event allergic reactions 11 53 followed hypotension 6 29 conclusion tpe safe tolerable manageable complications experienced hands article protected copyright rights reservedpmid34173719 doi101111 1744998713703,0.0
initial treatment strategy clinical outcomes finnish ms patients propensitymatched study j neurol 2021 jun 25 doi 101007 s00415021106739 online ahead printabstractbackground optimal treatment strategy diseasemodifying therapies dmts relapsingremitting multiple sclerosis rrms remains uncertainobjective compare outcomes initial treatment infusion therapies starting therapy medium efficacy therapy propensitymatched cohort finnish rrms patientsmethods total 154 rrms patients initiating natalizumab alemtuzumab ocrelizumab rituximab first dmt high efficacy dmt hedmt group 1771 patients initially treated injectable therapies teriflunomide dimethylfumarate escalated based disease activity moderate efficacy dmt medmt group identified finnish ms registry nearest neighbor propensity matching 11 caliper 01 performed age sex baseline expanded disability status scale edss annual relapse rate arr one year prior dmt time since ms symptom onset primary outcome time 6month confirmed edss progression secondary outcome time first relapseresults propensitymatched group comparisons probability 6month confirmed disability progression cdp 5 years dmt start 284 95 ci 157393 hedmt group n 66 470 95 ci 331581 medmt group n 66 p 0013 probability relapse 5 years 346 95 ci 241436 hedmt n 105 472 95 ci 366561 medmt n 105 p 0019conclusions initiating mstherapy hedmt significantly reduced risk 5year disability progression relapse compared using medmt first dmt choice propensitymatched groups finnish mspatientspmid34170403 doi101007 s00415021106739,0.0
case report delayed alemtuzumabinduced concurrent neutropenia thrombocytopenia relapsingremitting multiple sclerosis j pharm pract 2021 jun 258971900211021235 doi 101177 08971900211021235 online ahead printabstractalemtuzumab anticd52 monoclonal antibody used treat relapsingremitting multiple sclerosis following failure secondline medications administered intravenously 2 treatment sequences 1 year apart drug frequently associated mild infusion reactions within days administration increased infection risk long term adverse events secondary autoimmunity alemtuzumabinduced serious immunemediated thrombocytopenia itp wellreported occurred 1022 participants initial phase 2 3 trials multiple sclerosis significant neutropenia however rare observed 01 study participants delayed neutropenia itp thought occur secondary autoimmunity case reports described severe neutropenia occurring beyond 2 months last alemtuzumab dose present unusual case delayed combined neutropenia thrombocytopenia occurred 15 months second infusion alemtuzumab patient asymptomatic presented following discovery neutropenia thrombocytopenia routine laboratory studies patient responded steroids initially discharged although outpatient cell counts subsequently revealed recurrent neutropenia itp adverse drug reaction probability naranjo scale completed showed probable likelihood adverse event alemtuzumabrelated long term screening delayed hematologic abnormalities least 4 years initial dose necessary using alemtuzumab greater research needed understand mechanism drugassociated neutropeniapmid34169768 doi101177 08971900211021235,0.0
increased risk endstage renal disease patients systemic sclerosis scand j rheumatol 2021 jun 2518 doi 101080 0300974220211917143 online ahead printabstractobjective systemic sclerosis ssc systemic autoimmune disease affecting multiple organs including kidneys lack longterm renal prognosis studies patients ssc aim study assess risk endstage renal disease esrd patients sscmethod designed prospective cohort study based national health insurance research database taiwan patients ssc nonssc control group selected 1 january 2000 31 december 2013 ssc cohort control group matched propensity score 12 ratio primary outcome development esrd cox proportional hazard regression performed assess effects ssc esrdresults propensity score matching enrolled 2012 patients ssc group 4024 patients control group mean followup 65 years 86 individuals ssc group n 41 204 control group n 45 112 developed esrd risk esrd ssc group approximately two times higher control group hazard ratio hr 212 95 confidence interval ci 139324 subgroup analysis revealed higher risk esrd predominantly males hr 414 95 ci 197871 younger population hr 709 95 ci 2312180 conclusion significantly higher risk esrd among ssc patients among general population males younger generations vulnerable groupspmid34169793 doi101080 0300974220211917143,0.0
meningeal b cell clusters correlate submeningeal pathology natural model multiple sclerosis j immunol 2021 jun 23ji2000514 doi 104049 jimmunol2000514 online ahead printabstractmultiple sclerosis ms idiopathic demyelinating disease meningeal inflammation correlates accelerated disease progression study meningeal inflammation ms limited constrained access ms brain spinal cord specimens lack experimental models recapitulating progressive ms unlike induced models spontaneously occurring model offer unique opportunity understand ms immunopathogenesis provide compelling framework translational research propose granulomatous meningoencephalomyelitis gme natural model study neuropathological aspects ms gme idiopathic progressive neuroinflammatory disease young dogs female bias gme cases examined study meninges displayed focal disseminated leptomeningeal enhancement magnetic resonance imaging correlated heavy leptomeningeal lymphocytic infiltration leptomeningeal infiltrates resembled tertiary lymphoid organs containing large b cell clusters included proliferating ki67+ cells plasma cells follicular dendritic reticular cells germinal center b celllike cells b cell collections confined specialized network collagen fibers associated expression lymphoorganogenic chemokines cxcl13 ccl21 although neuroparenchymal perivascular infiltrates contained b cells lacked immune signature aggregates meningeal compartment finally meningeal b cell accumulation correlated significantly cortical demyelination reflecting neuropathological similarities ms hence chronic neuroinflammation meningeal microenvironment sustains b cell accumulation accompanied underlying neuroparenchymal injury indicating gme novel naturally occurring model study compartmentalized neuroinflammation associated pathology thought contribute progressive mspmid34162727 doi104049 jimmunol2000514,1.0
t cells growing universe roles neurodegenerative diseases neuroscientist 2021 jun 2310738584211024907 doi 101177 10738584211024907 online ahead printabstractt cells play central role homeostasis host defense infectious diseases t cell dysregulation can lead recognizing selfantigens foreign antigens causing detrimental autoimmune response t cell involvement multiple sclerosis ms long understood autoimmunemediated neurodegenerative disease well characterized recently role t cells also identified neurodegenerative diseases alzheimers disease ad parkinsons disease pd amyotrophic lateral sclerosis als interestingly several alleles variants human leukocyte antigen hla genes classified ad pd risk genes hla codes components major histocompatibility complex mhc class class ii expressed microglia innate immune cells central nervous system cns thus microglia t cells may potentially interact antigendependent independent fashion shape inflammatory cascade occurring neurodegenerative diseases dissecting antigen specificity t cells may lead new options diseasemodifying treatments neurodegenerative diseases review current understanding t cells neurodegenerative diseases summarize subsets t cells phenotype potential functions animal models human studies neurodegenerative diseasespmid34160330 doi101177 10738584211024907,0.0
development clinical application tumorderived exosomes patients cancer curr stem cell res ther 2021 jun 22 doi 102174 1574888x16666210622123942 online ahead printabstracta tumor abnormal growth cells within tissue can lead death due late diagnosis poor prognosis drug resistance finally enhanced metastasis formation exosomes nanovesicles derived different cell types vesicles can transfer various molecules including distinct form nucleic acids mrna mirna circrna proteins tumorderived exosomes texs exceptionally important roles multiple molecular cellular pathways like progression tumorigenesis drug resistance well metastasis texs detectable body fluids serum urine convenient noninvasive way access nanosized vesicles texs lead symptom expression genetic aberrations tumor cell population making accurate sensitive biomarker diagnosis prognosis tumors hand texs contain major histocompatibility complexes mhcs play important dual roles regulating tumor immune responses can mediate immune activation suppression tumorassociated immunity despite numerous scientific studies still many technical barriers distinguish texs nontumorderived exosomes removing exosomes lead wide difference outcomes inside patients body hence controversial pieces evidence demonstrated vital role texs hopeful biomarkers early detection cancers evaluation therapeutic effects monitoring patientpmid34161212 doi102174 1574888x16666210622123942,0.0
clinical correlates chair sit stand performance people multiple sclerosis physiother theory pract 2021 jun 22112 doi 101080 0959398520211931590 online ahead printabstractobjective study aimed evaluate motor nonmotor factors associated sittostand performance people multiple sclerosis pwms design observational crosssectional study subjects total 88 individuals ms participated study main measures standing performance measured using fivetimessittostand test ftsts berg balance scale assess balance 10meter walking test 10mwt used assess walking speed patient determined disease steps pdds used assess disability level furthermore brief international cognitive assessment ms bicams used assess cognitive status hospital anxiety depression scale hads assess depression anxiety modified fatigue impact scale mfis evaluate fatigue spearman correlation coefficient used determine relationship variables ftsts furthermore multiple linear regression conducted determine predictive factors ftsts results ftsts score correlated significantly bbs pdds bicams 10mwt mfis r ranged 03 052 p 05 however significant correlation observed ftsts hadsdepression hadsanxiety considering multiple regression analysis following factors significantly predictive ftsts 10mwt mfis bicamsz score r2 0433 p 0001 conclusion study concludes sit stand multifactorial potentially associated walking speed cognitive function fatigue factors considered healthcare professionals interpreting sittostand performance pwms designing rehabilitation interventionspmid34156901 doi101080 0959398520211931590,0.0
t cell transgressions tales t cell form function diversedisease states int rev immunol 2021 jun 21142 doi 101080 0883018520211921764 online ahead printabstractinsights t cell form function dysfunction rapidly evolving t cells remarkably varied effector functions including protecting host infection activating cells innate immune system releasing cytokines chemokines heavily contributing immunological memory healthy conditions t cells orchestrate finely tuned attack invading pathogens minimizing damage host dark side t cells also exhibit autoreactivity inflict harm host cells creating autoimmunity mechanisms t cell autoreactivity complex dynamic emerging research elucidating mechanisms leading t cells become autoreactive responses cause contribute diverse disease states peripherally within central nervous system review provides foundational information t cell development differentiation functions key t cell subtypes cytokines create effector roles sex differences highlighted pathological t cell contributions diverse peripheral central disease states arising errors reactivity highlighted focus multiple sclerosis rheumatoid arthritis osteoarthritis neuropathic pain type 1 diabetespmid34152881 doi101080 0883018520211921764,0.0
participant experiences eight weeks supervised homebased pilates among people multiple sclerosis qualitative analysis disabil rehabil 2021 jun 1918 doi 101080 0963828820211939446 online ahead printabstractpurpose exploratory qualitative study investigating participants experiences feasibility study supervised homebased pilatesmethods 10 females participated eightweek supervised n 4 homebased pilates n 6 program invited agreed interviewed data collected via semistructured interviews researcher observations participant experiences data analysed using codebook thematic analysis frameworkresults two domain summaries emerged 1 suitability homebased pilates particular population participants indicated supervised homebased pilates safe intensityappropriate implementable exercise method improve mental health outcomes among persons multiple sclerosis pwms 2 benefits experienced pwms participating pilates homebased pilates reduced exercise participation accessibility barriers commonly experienced pwms furthermore pwms reported improvements mental health outcomes following pilates exercise environmentsconclusions pwms reported experiencing improved mood following regular pilates training indicated homebased particular reduced barriers regularly experienced population results support pilates feasible exercise modality providing potential mood improvements among pwms future appropriately powered homebased randomised controlled trials explore effects pilates training mental health among pwms minimaltomild mobility disability warrantedimplications rehabilitationparticipants study described mental health benefits experienced engaging pilates nontraditional exercise modalityhomebased pilates overcame participatory accessibility barriers exercise among people multiple sclerosis ms participants valued pilates low intensity exacerbate fatiguehomebased pilates feasible exercise method people ms minimaltomild mobility disabilitypmid34151667 doi101080 0963828820211939446,0.0
palliative care intervention trials adults living progressive central nervous system diseases caregivers systematic review j pain symptom manage 2021 jun 17s08853924 21 003869 doi 101016 jjpainsymman202106010 online ahead printabstractcontext interest implementing palliative care adults living progressive central nervous system diseases pcnsd caregivers increasingobjectives inform evidencebased practice future research critically evaluating randomized clinical trials rcts investigating palliative care interventions pcis adults living pcnsd caregivers using selfreported outcomes patient caregiverreported outcome measures employedmethods systematic search using prisma methods embase pubmed scopus web science databases using index keyword methods articles published inception 28 february 2021 performed rcts investigating pci primary aim using patient caregiverreported outcomes assess pci effectiveness adults living pcnsd caregivers included qualitative synthesisresults five rcts met criteria used 21 unique outcome measures pooled patient diagnoses included multiple sclerosis motor neuron disease movement disorders primarily parkinsons disease 5 rcts assessed pci effectiveness patient symptom burden caregiver burden 3 rcts used patient qol primary outcome overall risk bias low pooled positive findings limited modest changes patient qol specific physical symptoms caregiver burden outcome measures lacked clinimetric responsiveness detect change whether caused disease intervention patient caregiverconclusion sparse lowcertainty evidence pci impact patient qol symptom burden caregiver burden indicate future research consider refining study populations interventions outcomes assessed outcome measures detect change due pcipmid34147576 doi101016 jjpainsymman202106010,0.0
understanding polyomavirus cns disease perspective mouse models febs j 2021 jun 19 doi 101111 febs16083 online ahead printabstractjc polyomavirus jcpyv ubiquitous human pathogen causes several devastating brain diseases immune compromised individuals notable jcpyvassociated cns diseases frequently fatal demyelinating brain disease progressive multifocal leukoencephalopathy pml pml aidsdefining disease precart epoch emerged lifethreatening complication patients receiving immunomodulatory agents autoimmune inflammatory disorders treatment certain hematological malignancies among rapidly expanding list pmlassociated biologics natalizumab tysabri highest incidence ominous sequela multiple sclerosis ms patients otherwise benefit dramatic reductions relapses using immunomodulatory agent drug withdrawal therapeutic option pml often complicated highmortality cerebral inflammatory reaction antijcpyv agents available lack tractable animal model polyomavirusinduced central nervous system cns disease acknowledged bottleneck elucidating pml pathogenesis immunological mechanisms control jcpyv vivo evaluation agents inhibit polyomavirus replication tissue culture uncovering early events presage jcpyvassociated neuropathology natural virushost mouse polyomavirus mupyv model recently developed explore mechanisms polyomavirusassociated cns disease review will cover benefits using mupyv model answer fundamental questions innate adaptive immune control jcpyv impact immunomodulation jcpyv pathogenesis mupyv cns infection model will help improve criteria identifying patients risk jcpyvassociated cns diseases development irreversible lesionspmid34145975 doi101111 febs16083,1.0
disability assessment using google maps neurol sci 2021 jun 17 doi 101007 s10072021053897 online ahead printabstractobjectives evaluate concordance google maps application gm clinical practice measurements ambulatory function eg ambulation score respective expanded disability status scale edss people multiple sclerosis pwms materials methods crosssectional multicenter study edss calculated using gm routine clinical methods correspondence two methods assessed multinomial logistic model investigated demographic age sex clinical features eg disease subtype fatigue depression might influenced discrepancies two methodsresults two hundred fortythree pwms included discrepancies edds assessments gm routine clinical methods found 81 243 333 74 243 304 pwms respectively progressive phenotype odds ratio 28 95 confidence interval ci 11711 p 003 worse fatigue 103 95 ci 101106 p 001 severe depression 11 95 ci 104117 p 0002 associated discrepancies gm routine clinical scoringconclusion gm easily used reallife clinical setting calculate related edss scores gm considered validation clinical studiespmid34142263 doi101007 s10072021053897,0.0
level kisspeptin10 patients multiple sclerosis association third ventricle diameter size vitamin d level physiol int 2021 jun 16202100179 doi 101556 2060202100179 online ahead printabstractobjective multiple sclerosis ms chronic progressive neurological disease affecting central nervous system cns studies report association ms pathogenesis cytokines aimed determine evaluate serum kisspeptin10 level ms patients related clinic parametersmaterials methods total 92 participants 46 patients relapsingremitting ms mean age 3892 1476 22 men 24 women 46 healthy controls mean age 3704 1549 22 men 24 women enrolled study ms patients neurologically examined magnetic resonance imaging mri performed clinical data neuropathic pain expanded disability status scale edss score etc patients demographic characteristics recorded serum level kisspeptin10 analyzed enzymelinked immunosorbent assay elisa methodresults level kisspeptin10 measured 2305 2781 ng ml ms patients 9342 9483 ng ml controls ms patients significantly lower kisspeptin10 levels controls p 0000 kisspeptin10 highest diagnostic value area curve auc 0881 95 confidence interval ci 08120950 cutoff value 2470 sensitivity 8040 specificity 7287 ms group furthermore kisspeptin10 level negatively correlated third ventricle diameter tvd p 0048 vitamin d concentration p 0004 significant difference determined kisspeptin10 clinical parametersconclusion potential prognostic biomarker serum kisspeptin10 level significantly lower patients ms without moreover observed negative correlations vitamin d tvd size kisspeptin10 think comprehensive studies needed verify elucidate issuepmid34138749 doi101556 2060202100179,0.0
functional reach test people multiple sclerosis reliability validity study physiother theory pract 2021 jun 17115 doi 101080 0959398520211938308 online ahead printabstractbackground limits stability los major component balance dysfunction people multiple sclerosis ms functional reach test frt clinical los assessment however psychometric properties investigated people ms yet objectives investigate 1 intrarater interrater testretest reliability frt people ms 2 minimum detectable change mdc frt distances 3 concurrent discriminant validity frt 4 cutoff distance best discriminates people ms healthy people fallers nonfallers msmethods fortythree people ms 36 healthy people participated study frt administered along instrumented los test berg balance scale four square step test timed go test expanded disability status scale frt repeated rater 2 min first test session determine intrarater reliability simultaneously conducted two independent raters determine interrater reliability frt also repeated 710 days determine testretest reliability reliability quantified using intraclass correlation coefficients icc blandaltman plots mdc validity assessed correlating frt distances scores measures comparing frt distances ms group healthy people fallers nonfallers ms groupresults frt demonstrated good excellent intrarater interrater testretest reliability icc 3 1 080088 p 001 icc 3 2 094097 p 001 icc 2 3 084086 p 001 respectively blandaltman analyses showed systematic bias assessments mdc 828 centimeters frt correlated outcome measures correlation coefficients ranged 031 079 p 05 significant differences frt distances found people ms healthy people however significant difference found fallers nonfallers ms p 001 p 09 respectively cutoff distance 355 centimeters best discriminates healthy people people ms 285 centimeters discriminate fallers nonfallers msconclusions frt reliable valid easytoadminister tool assessing los people mspmid34137673 doi101080 0959398520211938308,0.0
happens fingolimod discontinuation multicentre reallife experience j neurol 2021 jun 16 doi 101007 s00415021106588 online ahead printabstractobjective analyse course multiple sclerosis ms fingolimod withdrawal multicentre cohortmethods patients discontinued fingolimod included relapses expanded disability status scale edss new gadoliniumenhancing lesions magnetic resonance imaging mri assessed last year fingolimod year discontinuation wilcoxon test used analyse difference edss relapses two periods compare lymphocyte counts discontinuation 3 months later demographic clinical variables evaluated using univariable multivariable logistic regression analysesresults patients 230 females 661 mean age 38 years median edss 3 fingolimod discontinued due inefficacy 57 874 started another treatment relapse observed 33 patients year discontinuation severe reactivation observed 15 first 6 months discontinuation new enhancing lesions seen 62 116 patients higher age fingolimod discontinuation found associated lower probability inflammatory activity p 0001 severe reactivation p 0007 year discontinuation lower lymphocyte count risk factor clinical radiological severe activity p 002 p 0002 p 001 respectively conclusions main reason discontinuation fingolimod inefficacy onethird patients relapse year discontinuation 15 experienced severe reactivation approximately 50 patients available mri scan new enhancing lesions risk factors disease activity discontinuation low lymphocyte count younger agepmid34136943 doi101007 s00415021106588,0.0
assessing accuracy reproducibility parietal deep learning brain extraction algorithm j magn reson imaging 2021 jun 16 doi 101002 jmri27776 online ahead printabstractbackground manual brain extraction magnetic resonance mr images timeconsuming prone intra interrater variability several automated approaches developed alleviate constraints including deep learning pipelines however methods tend reduce performance unseen magnetic resonance imaging mri scanner vendors different imaging protocolspurpose present evaluate clinical use parietal pretrained deep learning brain extraction method compare reproducibility scan rescan analysis robustness among scanners different manufacturersstudy type retrospectivepopulation twentyone subjects 12 women age range 2248 years acquired using three different mri scanner machines including scan rescan themfield strength sequence t1weighted images acquired 3t siemens magnetization prepared rapid gradientecho sequence two 15 t scanners philips ge spinecho spoiled gradientrecalled spgr sequences respectivelyassessment analysis intracranial cavity volumes obtained subject three different scanners scan rescan acquisitionsstatistical tests parametric permutation tests differences volumes rank statistically evaluate performance parietal compared stateoftheart methodsresults mean absolute intracranial volume differences obtained parietal scan rescan analysis 188 ml 391 ml 471 ml siemens ge philips scanners respectively parietal bestranked method siemens ge scanners decreasing rank 2 philips images intracranial differences subject scanners 546 ml 2716 ml 3044 ml ge philips siemens philips siemens ge comparison respectively permutation tests revealed parietal always rank 1 obtaining similar volumetric results scannersdata conclusion parietal accurately segments brain generalizes images acquired different sites without need training finetuning parietal publicly availablelevel evidence 2 technical efficacy stage 2pmid34137113 doi101002 jmri27776,0.0
systemlevel variation multiple sclerosis care outcomes initial findings multiple sclerosis continuous quality improvement research collaborative popul health manag 2021 jun 16 doi 101089 pop20210040 online ahead printabstractmultiple sclerosis ms 3c complex chronic costly condition common disabling neurological illness affecting approximately 1 million adults united states ms studied basic science individual population levels system level assess smallarea variation effects ms population health outcomes systemlevel effects observed 3c conditions including cystic fibrosis rheumatoid arthritis inflammatory bowel disease authors report systemlevel variation findings baseline period first year multiple sclerosis continuous quality improvement mscqi study stepwise binary logistic regression analyses conducted investigate systemlevel smallarea variation effects ms relapses exacerbations diseasemodifying therapy dmt utilization brain mri utilization controlling demographics age sex potential confounders significant differences observed people ms pwms centers number demographic disease characteristics including sex age ms subtype controlling factors significant systemlevel effects observed outcomes including dmt utilization mri utilization relapses significant relationships also observed outcomes urgent care utilization including emergency department visits hospitalizations initial study provides evidence establishing presence systemlevel variation effects ms outcomes multicenter population study pwms get care can influence outcomes results support continued systemslevel research improvement initiatives optimize ms population health outcomes challenging costly complex chronic conditionpmid34134513 doi101089 pop20210040,0.0
association exposure particulate matters multiple sclerosis systematic review metaanalysis neuroimmunomodulation 2021 jun 1617 doi 101159 000516559 online ahead printabstractthe association air pollution multiple sclerosis ms entirely clear metaanalysis aimed determining correlation particulate matter pm 25 pm10 ms incidence relapse literature search performed embase web science pubmed gray literature sixteen articles retrieved ten articles included evaluated three measures association used metaanalysis odds ratio crosssectional casecontrol studies incidence rate ratio hazard ratio cohort studies metaanalysis 3 studies pm25 indicated exposure pm25 associated ms relapse incidence 95 confidence interval ci 1178 1102 1279 p 005 also assessment risk ratio studies showed correlation pms pm10 pm25 ms incidence relapse 95 ci 128 113143 p 005 collectively found pm exposure pm10 pm25 ms patients associates occurrence relapse diseasepmid34134109 doi101159 000516559,0.0
validation brief international cognitive assessment multiple sclerosis bicams russian population j int neuropsychol soc 2021 jun 1618 doi 101017 s1355617721000722 online ahead printabstractobjective cognitive dysfunction common multiple sclerosis ms brief international cognitive assessment ms bicams battery tests suggested measure evaluation cognitive status ms patients study aims validate bicams battery russian population ms patientsmethods age sexmatched ms patients n 98 healthy individuals n 86 included study symbol digit modalities test sdmt california verbal learning test 2nd edition cvltii brief visuospatial memory test revised bvmtr administered participants battery readministered 1 month later 44 ms patients investigate testretest reliabilityresults ms patients exhibited significantly lower performance testing bicams control group three neuropsychological tests testretest reliability good sdmt cvltii r 82 r 85 respectively adequate bvmtr r 70 based proposed criterion impairment z score 15 sd mean control group found 34 98 35 ms patients found impaired least one cognitive domain patients expanded disability status scale score 35 performed significantly worse controls sdmt p 0001 cvltii p 03 bvmtr p 0004 30 scores notconclusion study demonstrates bicams battery valid instrument identify cognitive impairment ms patients can recommended routine use russian federationpmid34132190 doi101017 s1355617721000722,0.0
managing chronic disease covid19 pandemic elearning application promote healthy lifestyle persons multiple sclerosis psychol health med 2021 jun 1518 doi 101080 1354850620211939072 online ahead printabstractehealth applications can support continuing care persons chronic diseases multiple sclerosis ms developed webbased mobile app called viola used home persons ms pwms previously participated innovative multidisciplinary rehab program purpose viola reinforce participants learned healthy lifestyle keep motivated adhere rehabilitation programs outbreak covid19 pandemic severely curtailed pwms contact usual health providers quickly updated viola grant continuity care homebound patientsby monitoring pwms subscriptions individual modules found definite increase national lockdown declared subscribers rated app positivelyencouraged positive feedbacks planning extend access app also pwms prior specific learning experience limit psychophysical consequences lockdown furthermore viola effective maintaining proper lifestyle contributing improve quality life pwmsviola potential increasing adherence pwms rehabilitation confirming digital communication tools valuable solution homebound pmid34130565 doi101080 1354850620211939072,0.0
acute bilateral optic chiasm neuritis longitudinal extensive transverse myelitis longstanding stable multiple sclerosis following vectorbased vaccination sarscov2 j neurol 2021 jun 15 doi 101007 s0041502110647x online ahead printno abstractpmid34131771 doi101007 s0041502110647x,0.0
description preliminary experience virtual visit assessment viva covid19 pandemic structured virtual management protocol patients multiple sclerosis neurol sci 2021 jun 15 doi 101007 s10072021053713 online ahead printabstractin people multiple sclerosis pwms strict followup essential telemedicine potential overcome many difficulties routine management herein present structured protocol can used remotely manage patients ms describing detail steps taken exams needed stage working group established developed tailored protocol can adapted variety settings overall protocol consisted 5 phases enrolment document sharing phase preevaluation virtual visit postvisit phase divided 14 individual steps october 2020 25 virtual visits carried via skype patients caregiver present visits active role average duration virtual visit 24 min previsit postvisit around 15 min overall satisfaction rated physicians considered high 80 05 using system usability scale sus patients also favorably rated virtual visit 966 61 20 cases virtual visit sufficient provide adequate information inperson clinical visit recommended described protocol potential provide benefits healthcare system well patients caregivers beyond covid19 pandemicpmid34131815 doi101007 s10072021053713,0.0
pythagorean selfawareness intervention multiple sclerosis patients quasiexperimental pragmatic trial arch clin neuropsychol 2021 jun 15acab044 doi 101093 arclin acab044 online ahead printabstractobjective multiple sclerosis ms autoimmune disorder central nervous system affecting patients wellbeing quality life pythagorean selfawareness intervention psai novel nonpharmaceutical intervention significant benefits ms chronic diseases study longstanding effectiveness psai investigatedmethod twoarm quasiexperimental pragmatic trial relapsingremitting ms patients 23 psai 21 control group psai patients received 8week training period performed psai home another 16 weeks assessments took place baseline 8 weeks 24 weeks included cognition fatigue perceived stress hair cortisolresults significant group time interactions favoring psai found first 8week period information processing speed fatigue perceived stress however verbal memory found significantly improved psai group 24week followup period significant group time differences respect hair cortisol side effects noted compliance excellentconclusions psai mostly effective first 8week training period benefits worn nontraining period albeit observed delayed significant improvement verbal memory findings will help refine technique either extending training period including booster sessions throughout psai treatment study provided class iii evidence psaipmid34128954 doi101093 arclin acab044,0.0
reliability validity sixspot step test ssst stroke survivors eur j phys rehabil med 2021 jun 15 doi 1023736 s197390872106799x online ahead printabstractbackground sixspot step test ssst originally developed assess walking ability challenging balance walking patients multiple sclerosis provides comprehensive information ambulatory abilities several existing measures timed go test tug test functional gait assessment dynamic gait index assess advanced balance control ability stroke survivors modified ssst serve purposeaim aim study expand current understanding psychometric properties ssst using healthy older adults stroke survivorsdesign study adopted experimental designsetting universityaffiliated neurorehabilitation laboratorypopulation total 50 study participants including 25 chronic stroke survivors 25 healthy older adults recruited communitymethods ssst administered stroke survivors twice day 1 2 1week interval fuglmeyer assessment lower extremities fmale berg balance scale bbs limit stability los test timed go test tug test chinese version community integration measures cimc assessed day 1 random order healthy control group assessed sixspot step test day 1results ssst showed excellent interrater intrarater testretest reliability intraclass correlation coefficient095 p0001 significant correlations found ssst performance fmale results r0517 p005 bbs scores q r 0531 p005 tug test scores r 0828 p0001 mdc mean ssst time affected leg unaffected leg stroke survivors 605s cutoff time 1011s sensitivity 80 specificity 92 kicking obstacles affected leg 1018s sensitivity 80 specificity 92 kicking obstacles unaffected legconclusions ssst reliable test showed significant correlation fmale scores bbs scores tug test times stroke survivorsclinical rehabilitation impact ssst can used assess advanced balance control stroke survivorspmid34128605 doi1023736 s197390872106799x,0.0
apoe4positive multiple sclerosis patients likely cognitive impairment crosssectional study neurol sci 2021 jun 12 doi 101007 s1007202105383z online ahead printabstractbackground multiple sclerosis ms presents wide variety symptoms including cognitive dysfunction previous studies terms possible function apoe4 allele risk factor cognitive dysfunction ms patients associated conflicting results role 4 isoform apolipoprotein apoe4 investigated study risk factor cognitive dysfunction ms patientsmethods mildly disabled relapsingremitting ms rrms patients involved study neurocognitive assessment conducted minimal assessment cognitive function ms macfims battery determining genotype patients divided two groups apoe4positive apoe4negative groups cognitive findings comparedresults seventyone patients mean age 3143 875 involved study eleven 17 6470 patients apoe4positive group least one impaired test rate 16 54 2962 apoe4negative group p 001 rate overall cognitive impairment failure 2 tests statistically different groups study p 075 impairment paced auditory serial addition test pasat task also mean score brief visuospatial memory testrevised bvmtr tests different two groups p 001 002 respectively conclusion ms apoe4positive patients likely least one impaired cognitive test need studies larger sample sizes based msspecific cognitive tests confirm findingspmid34120271 doi101007 s1007202105383z,0.0
first manifestation multiple sclerosis immunization pfizerbiontech covid19 vaccine j neurol 2021 jun 11 doi 101007 s0041502110648w online ahead printno abstractpmid34115170 doi101007 s0041502110648w,0.0
multiple sclerosis experiences couples examination patient partner perspectives j health psychol 2021 jun 1113591053211017192 doi 101177 13591053211017192 online ahead printabstractthe study aims investigate multiple sclerosis ms experiences couples using dyadic qualitative method separate simultaneous interviews conducted 20 couples including one partner ms themes resulting content analysis examined two categories convergent anxiety future acceptance ms ms accelerator relationship divergent sexual problems experience ms symptoms priority problems untold issues findings revealed shared unique perspectives partners illness process potential guide psychosocial interventions couples living chronic illnesspmid34111986 doi101177 13591053211017192,0.0
10weeks resistance training improves sleep quality cardiac autonomic control persons multiple sclerosis disabil rehabil 2021 jun 919 doi 101080 0963828820211934738 online ahead printabstractpurpose examine acute chronic effects 10weeks progressive resistance training sleep quality sleeping heart rate variability persons multiple sclerosis pwms methods eighteen pwms age 448 106 years edss 31 17 completed 10week resistance training three training sessions per week session consisted 4 lower body exercises performing 24 sets exercise 815 repetitions set intensity ranging 60 75 1repetition maximum subjective actigraphic sleep quality sleeping heart rate variability carried 4 different times 1 starting intervention rest day 2 night training week 1 3 night training week 10 4 completing resistance training program rest dayresults regarding subjective sleep quality significant main effects observed variables sleep quality sleep comfort easy falling sleep easy waking felling rest sleep quality sleep comfort easy falling sleep greater rest night week 1 vs rest night week 10 actigraphic sleep quality also improved training program rest night week 1 vs rest night week 10 pairwise comparison showed acute effect session training program rest night week 10 training night week 10 hf pnn50 rmmsdconclusions resistance training nonpharmacological treatment capacity improve regulation autonomic system consequently sleep quality pwmsimplications rehabilitation10 weeks resistance training improves sleep quality persons multiple sclerosisresistance training can modulate autonomic cardiac control populationimproving sleep quality essential persons ms close relationship variables symptomatic fatiguepmid34107841 doi101080 0963828820211934738,0.0
cognitive trajectories multiple sclerosis longterm followup study neurol sci 2021 jun 8 doi 101007 s10072021053562 online ahead printabstractbackground cognitive impairment occurs multiple sclerosis ms undergoes progressive worsening disease course however clinicians still struggle predict course cognitive function evaluate baseline clinical imaging predictors cognitive abilities worsening time performed latent trajectory analysis cognitive performances ms patients 15 years disease onsetmethods collected age sex education dominant nondominant 9hole peg test 9hp timed 25foot walk t25fw well mri measures grey matter volume lesion load within 6 months disease diagnosis relapsingremitting ms rrms patients diagnosis followup also assessed cognitive status symbol digit modalities test sdmt cognitive impairment defined applying age gender educationadjusted normative values groupbased trajectory analysis performed determine trajectories predictive value clinical imaging variables baseline assessed multinomial logistic regressionresults included 148 rrms 98 females 50 males 11 4 year followup 514 remained cognitively stable whereas 486 cognitively worsened cognitively worsening patients higher t25fw time p 0004 reduced hippocampal volume baseline p 004 conclusion physical disability well hippocampal atrophy might depict patients risk cognitive worsening disease course therefore using predictors clinicians may select patients carefully evaluate cognitive impairment eventually introduce cognitive rehabilitation treatmentspmid34105018 doi101007 s10072021053562,0.0
tnf inhibitors used steroidsparing maintenance monotherapy parenchymal cns sarcoidosis j neurol neurosurg psychiatry 2021 jun 8jnnp2020325665 doi 101136 jnnp2020325665 online ahead printabstractobjective assess efficacy tumour necrosis factor tnf inhibitors used steroidsparing monotherapy central nervous system cns parenchymal sarcoidosismethods french multiple sclerosis neuroinflammation centers retrospectively identified patients definite probable cns sarcoidosis treated tnf inhibitors steroidsparing monotherapy patients cns parenchymal involvement demonstrated mri imaging followup included primary outcome minimum dose steroids reached associated clinical imaging worsening minimum 3 months dosing changeresults identified 38 patients cns sarcoidosis treated tnf inhibitors 23 fulfilled criteria 13 females treatments infliximab n22 adalimumab n1 median iqr 24 1740 months treatment initiation mean sd age 415 105 years median iqr disease duration 22 14495 months overall 60 patients received immunosuppressive agents tnf inhibitor mean sd minimum dose steroids 315 33 mg tnf inhibitor initiation 65 55 mg p0001 65 patients achieved steroids dosing 6 mg day 61 showed clinical improvement 30 stability 9 disease worsening imaging revealed improvement 74 patients stability 26conclusion tnf inhibitors can greatly reduce steroids dosing patients cns parenchymal sarcoidosis even refractoryclassification evidence study provides class iv evidence tnf inhibitor used steroidsparing monotherapy effective patients cns parenchymal sarcoidosispmid34103339 doi101136 jnnp2020325665,0.0
sleep disorders patients multiple sclerosis spain neurologia 2021 jun 5s02134853 21 000803 doi 101016 jnrl202103012 online ahead printabstractobjective study assesses presence sleep disturbances relationship clinical demographic variables patients ms view establishing correlations different variables frequency sleep disturbancesmethods pittsburgh sleep quality index psqi used detect sleep disorders contacted patients treated ms unit distributed questionnaire psqi 221 patients receiving 142 usable questionnaires 8 30 september 2019results prevalence patients sleep disturbances study 747 737 women 768 men therefore sleep disorders pervasive patients ms 3 4 patients experiencing higher rate observed population without disease frequency sleep disorders gradually increased line age 2 age groups analyzed 4454 years 5568 years proportion moderate severe sleep disorders 428 539 respectively moderate severe sleep disturbances observed 275 447 583 patients expanded disability status scale scores 03 36 6 respectivelyconclusion results indicate sleep disorders common patients ms populations patients secondary progressive forms ms frequently present sleep disturbances patients primary progressive forms report less frequently age degree disability positively correlated prevalence severity sleep disorders ms patientspmid34103173 doi101016 jnrl202103012,0.0
associations neurofilament light chain levels disease activity brain atrophy progressive multiple sclerosis biomed pap med fac univ palacky olomouc czech repub 2021 jun 1 doi 105507 bp2021034 online ahead printabstractbackground neurofilament light chain promising biomarker disease activity treatment response relapsingremitting multiple sclerosis ms role progressive ms less clearaim aim study assess relationship plasma neurofilament light chain pnfl disease activity defined concept neda3 evident disease activity brain volumetry cohort patients progressive disease form pms methods levels pnfl simoa technology examined 52 pms patients analysed relationship neda3 status annual brain volume loss bvl last 12 months statistical model developed using logistic regression analysis including demographic clinical magnetic resonance imaging mri data independent variables dependent variables neda3 status bvlresults mean age study participants n52 50 females 4585 sd 982 median disability score 50 iqr 5055 roc analysis showed pnfl predicts neda3 sensitivity specificity model 778 876 respectively p0001 abnormal bvl sensitivity specificity 966 682 respectively p0001 conclusions results show pnfl levels useful biomarker disease activity determined neda3 status including brain mrivolumetry patients progressive form mspmid34092793 doi105507 bp2021034,0.0
euthanasia assisted suicide neurological diseases systematic review neurologia 2021 jun 2s02134853 21 000906 doi 101016 jnrl202104016 online ahead printabstractobjective identify neurological diseases euthanasia assisted suicide frequently requested countries medical procedures legal specific characteristics euthanasia diseases show evolution euthanasia figuresmethods conducted systematic literature reviewresults dementia motor neuron disease multiple sclerosis parkinsons disease neurological diseases frequently motivate requests euthanasia assisted suicide claims related dementia constitute largest group growing raise additional ethical legal issues due patients diminished decisionmaking capacity countries ratios euthanasia requests cases multiple sclerosis motor neuron disease huntington disease higher diseaseconclusions cancer neurological diseases frequent reason requesting euthanasia assisted suicidepmid34090721 doi101016 jnrl202104016,0.0
farnesol induces protection murine cns inflammatory demyelination modifies gut microbiome clin immunol 2021 jun 3108766 doi 101016 jclim2021108766 online ahead printabstractfarnesol 15carbon organic isoprenol synthesized plants mammals antioxidant antiinflammatory neuroprotective activities sought determine whether farnesol treatment result protection murine experimental autoimmune encephalomyelitis eae wellestablished model multiple sclerosis ms compared disease progression severity c57bl 6 mice treated orally 100 mg kg day farnesol solubilized corn oil cornoil treated untreated eae mice farnesol significantly delayed onset eae 2 days dramatically decreased disease severity 80 compared controls disease protection farnesol associated significant reduction spinal cord infiltration monocytesmacrophages dendritic cells cd4+ t cells significant gut change microbiota composition including decrease firmicutesbacteroidetes ratio study suggests fol protect ms patients cns inflammatory demyelination partially modulating gut microbiomes compositionpmid34091018 doi101016 jclim2021108766,1.0
hif1alpha crosstalk reactive oxygen species autophagy process review multiple sclerosis cell mol neurobiol 2021 jun 5 doi 101007 s10571021011115 online ahead printabstractcellular stress can lead production reactive oxygen species ros autophagy catabolic pathway protects cells stress autophagy turn plays pivotal role pathophysiology multiple sclerosis ms current review first summarized contribution ros autophagy ms pathogenesis probable crosstalk two pathways hif1 first time proposed hope employing better understanding ms pathophysiology probable therapeutic approachespmid34089426 doi101007 s10571021011115,0.0
experiences perceived outcomes persons multiple sclerosis participating randomized controlled trial testing implementation canadian physical activity guidelines adults ms embedded qualitative study disabil rehabil 2021 jun 419 doi 101080 0963828820211914199 online ahead printabstractpurpose describe experiences outcomes participants enrolled randomized controlled trial testing implementation canadian physical activity guidelines adults multiple sclerosismaterials methods fiftysix persons ms enrolled trial participated current study involved semistructured interview 16week followup interview data analyzed using thematic analysisresults 56 participants 26 ended enrolling communitybased exercise program specialized persons multiple sclerosis ms 7 joined another gym 4 trained home 17 took part specific program across study participants positive outcomes reported across number domains including mental function knowledge physical activity pa ms physical function advocacy pa peers daily participation body awareness enrolled communitybased program supportive inclusive environment critical pa experiences furthermore environmental supports particularly knowledgeable supportive trainers similar peers contributed largely positive mental changes increased knowledge gainedconclusions study provides support promotion pa persons ms development communitybased programs adapted people msimplications rehabilitationengaging regular physical activity associated many positive benefits outcomes people mssupportive elements community peers also ms adaptive equipment trainers knowledgeable ms especially important creating positive experiences including enjoyment desire engage regular physical activitythis study provides support advocacy eg persons ms directly referral communitybased exercise programs adapted people mspmid34086513 doi101080 0963828820211914199,0.0
vivo targeting neurovascular unit challenges advancements cell mol neurobiol 2021 jun 4 doi 101007 s10571021011133 online ahead printabstractthe bloodbrain barrier bbb essential homeostasis central nervous system cns functions bbb performed neurovascular unit nvu consists endothelial cells pericytes astrocytes microglia basement membrane neurons nvu cells interact closely together responsible neurovascular coupling bbb integrity transendothelial fluid transport studies shown nvu dysfunction implicated several acute chronic neurological diseases including alzheimers disease multiple sclerosis stroke mechanisms nvu disruption remain poorly understood partially due difficulties selective targeting nvu cells review discuss relative merits available protein markers drivers nvu along recent advancements made field increase efficiency specificity nvu researchpmid34086179 doi101007 s10571021011133,0.0
syndemics approach exercise medicine health london 2021 jun 313634593211021481 doi 101177 13634593211021481 online ahead printabstractthis paper offers new insights promotion exercise medicine eim framework mental illness chronic disease utilising syndemics framework posits mental health conditions corollaries social conditions argue medicalized exercise promotion paradigms ignore social conditions can contribute mental illness can contribute mental illness via discrimination worsening selfconcept based disability first address ways current eim framework may narrow scope considering impact social factors determinants health consider narrow scope combination emphasis independence individual prescriptions may serve reinforce stigma shame associated chronic disease mental illness draw examples two distinct research projects one exercise interventions depression one exercise interventions multiple sclerosis ms order consider ways improve approach exercise promotion related populationspmid34082584 doi101177 13634593211021481,0.0
selfefficacy training adjunct exercise person progressive multiple sclerosis case report physiother theory pract 2021 jun 3110 doi 101080 0959398520211934921 online ahead printabstractbackground increasing selfefficacy exercise minimizing diseaserelated barriers shown improve physical activity levels quality life qol persons multiple sclerosis ms currently little research examined exercise selfefficacy persons advanced ms purpose explore effects selfefficacy plus exercise intervention physical activity endurance level qol fatigue individual advanced ms low selfefficacymethods participant 60yearold severely disabled female secondary progressive ms expanded disability status score edss 8 8week intervention consisted weekly discussions msrelated education four oneonone sessions ms mentor daily journal record sleep quality fatigue level physical activity outcomes included modified 5meter walk test 5mwt ms impact scale msis29 exercise selfefficacy scale exes modified fatigue impact scale mfis ms selfefficacy scale msses patient health questionnaire9 phq9 daily physical activity monitoring outcomes assessed baseline week 0 postintervention week 8 8 weeks post intervention week 16 participant continued regular exercise routine independently throughout study periodresults notable improvements exes mfis phq9 msis29 psychological subscale sleep quality morning fatigue ratings post intervention retained follow upconclusion findings illustrate 8week selfefficacy intervention increased exercise selfefficacy qol reduced perceived fatigue severely disabled individual progressive ms future research examine selfefficacy interventions larger sample size persons progressive mspmid34081567 doi101080 0959398520211934921,0.0
postoperative outcomes following posterior lumbar fusion patients multiple sclerosis clin spine surg 2021 jun 3 doi 101097 bsd0000000000001212 online ahead printabstractsummary background multiple sclerosis ms chronic inflammatory disease can cause physical neurological dysfunction patients ms living longer undergoing orthopedic procedures risk patients ms undergoing posterior lumbar fusion plf studied literature beforeobjective study aims 1 analyze rates postoperative complications ms patients undergoing primary plf 2 analyze economic burden associated surgeries ms population compared patients without msmethods retrospective review medicare database conducted patients underwent plf posterior lumbar interbody fusion years 2006 2013 cases involving sameday anterior revision procedures patients history spine infection trauma neoplasm excluded study demographics comorbidities 90day postoperative complications cost length stay calculated outcomes interest analyzed using multivariate logistic regression adjusting age sex comorbidity burden significance defined pvalue 005results 2363 patients ms 23 569 matched controlled patients found significant increase risk sepsis odds ratio 185 p0034 urinary tract infection or189 p0001 deep vein thrombosis or14 p0044 90day emergency room visit or114 p0027 90day readmissions or120 p0011 compared patients without history ms patients ms also incurred 4379 extra total hospital charge 1679 increase cost hospitalization increase length stay 405 vs 361 p0001 conclusions diagnosis ms associated significant increase postoperative complications higher costs hospitalization imperative physicians understand risk factors patients undergoing plf posterior lumbar interbody fusion ms better counsel postoperative complications surgerylevel evidence level iiipmid34081657 doi101097 bsd0000000000001212,0.0
provider experience teleneurology academic neurology department telemed j e health 2021 jun 1 doi 101089 tmj20210096 online ahead printabstractbackground teleneurology become widely adopted severe acute respiratory syndrome coronavirus 2 pandemic however provider impressions teleneurology experience well described methods novel questionnaire developed collect provider impressions video teleneurology encounters providers university pennsylvania health system uphs neurology department n 162 asked complete questionnaire video teleneurology patient encounter april august 2020 individual patient encounterlevel data extracted electronic medical record results one thousand six hundred three surveys completed 55 providers response rate 1012 history obtained ability connect patient considered better inperson visit almost encounters quality physicianpatient relationship good excellent 93 overall experience inperson visit 73 visits better 12 sixtyeight percent respondents reported none elements neurological examination performed person changed assessment plan assessment visit better increased 83 april 89 july 95 august headache 91 multiple sclerosis neuroimmunology 96 movement disorder 89 providers highest proportion ratings better overall experience neuromuscular providers lowest 60 conclusions provider impressions teleneurology history examination providerpatient relationship favorable majority responses important differences emerge provider specialty visit characteristics groupspmid34077285 doi101089 tmj20210096,0.0
dating diagnosis lived experience people multiple sclerosis sex disabil 2021 may 26118 doi 101007 s11195021096989 online ahead printabstractmultiple sclerosis ms neurological condition usually manifests ages 2040 years critical period developing relationships particularly romantic relationships people ms can experience sexual dysfunction limb weakness fatigue pain reduced mood bladder bowel dysfunction potentially affecting ability participate many meaningful activities including associated romantic relationships dating engaging sexual intercourse dating starting romantic relationships can difficult people physical disabilities can experience stigma negative societal attitudes fear requiring care potential partners dating experiences people progressive conditions like ms explored detail aim study develop rich understanding living ms interacts influences dating developing romantic relationships study used descriptive phenomenological design purposive sampling strategy colaizzis descriptive phenomenological method used analyze data colaizzi 1978 five females two males aged 2351 participated two online focus groups dating diagnosis ms highly personal phenomenon characterized individual differences values experiences core phenomenon personal decisionmaking disclosure diagnosis ongoing adaptation fluctuating nature condition partners new developing relationships findings will help health professionals working adults ms understand important aspect livespmid34075262 pmcpmc8153848 doi101007 s11195021096989,0.0
computed tomographic study endodontic apical changes 81 equine cheek teeth sagittal fractures equine vet j 2021 jun 1 doi 101111 evj13475 online ahead printabstractbackground sagittal fractures equine cheek teeth commonly observed oral examination reports apical endodontic pathology associated fractures seen computed tomographic ct examinationobjectives document prevalence ct changes indicative apical disease equine cheek teeth suffered sagittal fracture involving clinical + reserve crownstudy design retrospective case seriesmethods ct examinations equine heads sagittal fractures cheek teeth present reviewed 81 teeth 49 horses identified sagittal cheek tooth fracture images evaluated apical pathology including gas endodontic system periapically widened periodontal space periapical sclerosis apical clubbing cementoma hypercementosis lamina dura loss associated sinusitis sinus mucosal swelling apical infection grading system created give tooth score hounsfield units used measure density endodontic apical periapical regions fracture length ratio recorded statistical analysis performed using generalised estimating equation evaluate predictors apical infection associations clinical signs ct abnormalitiesresults 87 sagittal fractures 56 buccal 17 palatal lingual 14 midline 81 teeth recorded 74 maxillary 7 mandibular apical infection diagnosed 73 37 51 p 005 buccal 55 6 11 p 007 palatal lingual 100 13 13 midline 100 6 6 multiple fractures 96 23 24 p 0008 fractures involving infundibula significant relationship apical infection presence clinical signs associated dental pathology p 04 significant association fracture length ratio apical infection p 10 midline sagittal fractures significantly associated sinusitis compared maxillary fractures 592 95 ci 186 1672083 p0006 loss lamina dura significantly associated apical infection p05 main limitations maxillary tooth bias subjective grading systemconclusions large proportion fractured cheek teeth evidence apical infection ct examination therefore warrant treatmentpmid34060137 doi101111 evj13475,0.0
considerations hand surgery patients scleroderma hand n y 2021 may 3115589447211017211 doi 101177 15589447211017211 online ahead printabstractsystemic sclerosis scleroderma ssc autoimmune disease causes significant dysfunction multiple organ systems including musculoskeletal system poses significant challenges hand surgeon including calcinosis ischemic changes raynaud phenomenon tendinopathies synovitis joint contractures patients ssc also suffer multiorgan dysfunction makes highrisk surgical patients hand surgeon must understand pathophysiology treatment strategies special operative considerations required population avoid complications help maintain improve hand functionpmid34053315 doi101177 15589447211017211,0.0
experiences quality life people multiple sclerosis wheelchair nurs open 2021 may 30 doi 101002 nop2956 online ahead printabstractaim study includes healthrelated quality life people norway multiple sclerosis live home wheelchair n 6 purpose show experience living chronic disease ms perceive situation value health leads positive consequences central studydesign study qualitative design show healthrelated experiences living msmethod interviews conducted home later transcribed interview guide openended questions used transcribed material analysed thematic analysisresults key themes free independent threat self ones identity adaptation ms free independent everyday life essential informants dependent others basic needs something sought avoid adapting new situation changing roles challenge required lot thempmid34053191 doi101002 nop2956,0.0
care consumption people multiple sclerosis multichannel sequence analysis populationbased setting british columbia canada mult scler 2021 may 2813524585211016726 doi 101177 13524585211016726 online ahead printabstractbackground persons multiple sclerosis pwms typically require complex multidisciplinary care rarely formally assessedobjectives applied multichannel sequence analysis mcsa identify care consumption patterns pwms british columbia canadamethods created two cohorts comprising incident prevalent ms cases using linked clinical administrative data applied mcsa quantify compare care pathways pwms based allcause hospitalizations physician visits divided five specialities care consumption clusters characterized using demographic clinical featuresresults 1048 incident 3180 prevalent pwms mcsa identified 12 6 distinct care consumption clusters median followup 96 130 years respectively large disparities clusters observed median number annual consultations ranged 56 213 general practitioners 12 46 neurologists 0 53 psychiatrists incident cohort characteristics ms symptom onset associated highest care consumption included high comorbidity burden older age similar disparities associations prevalent pwmsconclusion distinct patterns care consumption reminiscent heterogeneity ms may facilitate health service planning evaluation provide novel outcome measure health researchpmid34048293 doi101177 13524585211016726,0.0
contrasting brain imaging features mogantibody disease aqp4antibody nmosd multiple sclerosis mult scler 2021 may 2813524585211018987 doi 101177 13524585211018987 online ahead printabstractbackground identifying magnetic resonance imaging mri markers myelinoligodendrocytesglycoprotein antibodyassociated disease mogad neuromyelitis optica spectrum disorderaquaporin4 positive nmosdaqp4 multiple sclerosis ms essential establishing objective outcome measuresobjectives quantify imaging patterns central nervous system cns damage mogad remission stage compare nmosdaqp4 msmethods 20 mogad 19 nmosdaqp4 18 ms remission brain spinal cord involvement 18 healthy controls hc recruited volumetrics lesions cortical lesions diffusionimaging measures analysedresults deep grey matter volumes lower mogad p 002 ms p 00001 compared hc strongly correlated current lesion volume mogad r 093 p 0001 ms r 065 p 00034 cortical juxtacortical lesions seen minority mogad majority ms none nmosdaqp4 nonlesional tissue fractional anisotropy fa reduced ms p 001 although focal reductions noted nmosdaqp4 reflecting mainly optic nerve corticospinal tract pathwaysconclusion mogad patients left grey matter damage may related persistent white matter lesions nmosdaqp4 patients showed relative sparing deep grey matter volumes reduced nonlesional tissue fa observations study can used identify new markers damage future multicentre studiespmid34048323 doi101177 13524585211018987,1.0
role teriflunamide multiple sclerosis patient observational study psychol health med 2021 may 2718 doi 101080 1354850620211931371 online ahead printabstractteriflunomide drug immunosuppressive selective immunomodulatory action characterized antiinflammatory antiproliferative properties several clinical studies demonstrated efficacy safety drug multiple sclerosis estimating significant improvement cognitive performancethe aim study evaluate effects teriflunomide analysing correlation brain atrophy general cognitive profile evaluating longterm changes effect teriflunomide studied 30 patients multiple sclerosis 30 control subjects patients underwent full cognitive profile assessment using brief repeatable battery neuropsychological tests neuroimaging examination 30 t working scannerour results suggested treatment teriflunomide potentially slow accumulation microstructural tissue damage grey matter matter also better preserve cognitive profile particularly highlighting benefits memory domain thanks drug therapy brain volume patients remained constant leading improvements memory indicating teriflunomide neuroprotective potential strengthening evidence link loss brain volume cognitive impairmentpmid34044680 doi101080 1354850620211931371,1.0
elucidating distinct clinicoradiologic signatures borderland neuromyelitis optica multiple sclerosis j neurol 2021 may 27 doi 101007 s00415021106191 online ahead printabstractbackground separating antibodynegative neuromyelitis optica spectrum disorders nmosd multiple sclerosis ms borderline cases extremely challenging due lack biomarkers elucidating different pathologies within likely heterogenous antibodynegative nmosd ms overlap syndrome therefore major unmet need help avoid disability inappropriate treatmentobjective study aimed identify distinct subgroups within antibodynegative nmosd ms overlap syndromemethods twentyfive relapsing antibodynegative patients nmosd features underwent prospective brain spinal cord mri subgroups identified unsupervised algorithm based preselected nmosd ms discriminatorsresults four subgroups identified patients group 1 termed mslike n 6 often central vein sign cortical lesions 83 67 respectively patients group 2 spinal mslike 8 shortsegment myelitis mslike brain lesions group 3 classic nmolike 6 high percentage bilateral optic neuritis longitudinally extensive transverse myelitis letm 80 60 respectively normal brain appearance 100 group 4 nmolike brain involvement 5 typically history nmosdlike brain lesions letm compared groups group 4 significantly decreased fractional anisotropy nonlesioned tracts 046 vs 049 p 0003 decreased thalamus volume 084 vs 098 p 004 conclusions nmosd ms cohort contains distinct subgroups likely corresponding different pathologies requiring tailored treatment propose nonconventional mri might help optimise diagnosis challenging patientspmid34043042 doi101007 s00415021106191,0.0
editors#39 note effect ocrelizumab vaccine responses patients multiple sclerosis veloce study neurology 2021 may 4 96 18 869 doi 101212 wnl0000000000011869no abstractpmid34032591 doi101212 wnl0000000000011869,0.0
insights potential mechanisms action functional electrical stimulation therapy combination taskspecific training scoping review neuromodulation 2021 may 24 doi 101111 ner13403 online ahead printabstractobjectives scoping review undertaken synthetize appraise literature potential mechanisms action functional electrical stimulation therapy combination taskspecific training fest + tst rehabilitation following stroke spinal cord injury traumatic brain injury multiple sclerosismaterials methods literature search performed using multiple databases including apa psycinfo medline pubmed embase ccrct cochrane database systematic reviews 1946 june 2020 literature search used following terms spinal cord injury paraplegia tetraplegia quadriplegia stroke multiple sclerosis traumatic brain injury acquired brain injury functional electrical stimulation fes search included clinical preclinical studies without limits languageresults 8209 titles retrieved primary search 57 publications fulfilled inclusion exclusion criteria scoping review publications clinical studies n 50 seven preclinical studies using animal models results review suggest fest + tst can result multiple effects different elements muscle cerebral cortex however studies focused muscle changes fest + tstconclusions results scoping review suggest fest + tst can result multiple effects different elements neuromuscular system research studies focused muscle changes fest + tst despite efficacy fest + tst neurorehabilitation cns injury disease results review underline important knowledge gap regards actual mechanism action fest + tstpmid34031937 doi101111 ner13403,0.0
efficacy homebased selfadministered hand exercise program patients systemic sclerosis randomized controlled evaluatorblind clinical trial j clin rheumatol 2021 may 6 doi 101097 rhu0000000000001752 online ahead printabstractbackground patients systemic sclerosis ssc hand involvement underrated clinical manifestation therefore aim study investigate efficacy hand exercise program demonstrate effect hand function quality life anxiety depression patients sscmethods study designed single blind randomized controlled comparative study sixtytwo female patients ssc randomized exercise group n 32 control group n 30 lost followup 25 patients analyzed group exercise group 8week intervention consisted isometric hand exercises selfadministered stretching repeated 10 times 2 sets per day patients assessed using hand mobility scleroderma hamis test duruoz hand index dhi grip strength 36item short form health assessment questionnairedisability index haqdi beck anxiety inventory bai beck depression inventory bdi baseline 4 8 weeks later withingroup comparisons time analyzed using friedman test post hoc analysis performed using wilcoxon signed rank test multiple linear regression analysis used define impact exercise clinical statusresults 50 total patients median age median body mass index 555 years 259 kg m2 median disease duration 100 years thirtyfour patients 680 diffuse cutaneous systemic sclerosis dcssc whereas 16 320 limited cutaneous systemic sclerosis lcssc primary outcome handgrip strength well hamis dhi haqdi bdi significantly improved time p 0001 p 0001 p 0001 p 0001 p 0005 respectively betweengroup comparison indicated significant improvement dhi handgrip strength haqdi bai bdi exercise group p 002 p 0013 p 0001 p 0015 p 0036 respectively multiple linear regression analysis exercise found efficient factor affecting improvement hamis dhi haqdi grip strengthconclusions 8week intervention composed isometric hand exercises selfadministered stretching provided significant improvement handgrip strength general health quality life psychological status patients sscpmid34030163 doi101097 rhu0000000000001752,0.0
sirtuins pharmacological targets neurodegenerative neuropsychiatric disorders br j pharmacol 2021 may 24 doi 101111 bph15570 online ahead printabstracthistone deacetylases hdac enzymes regulate several processes transcription cell proliferation differentiation development hdacs classified either zn2+ dependent nad+ dependent enzymes experimental clinical evidence demonstrated along years hdacs modulation critical process neurodegenerative psychiatric disorders nevertheless studies focused role zn2+ dependent hdacs development diseases although growing evidence showing nad+ dependent hdacs known sirtuins also promising targets sense literature reports decreased levels nad+ cns disorders can lead alterations sirtuins activation therefore result increased pathology review discuss role sirtuins neurodegenerative neuropsychiatric disorders well possible rationales considered pharmacological targets future therapeutic interventionspmid34029375 doi101111 bph15570,0.0
multiple sclerosis clinic utilization associated fewer emergency department visits can j neurol sci 2021 may 24114 doi 101017 cjn2021118 online ahead printno abstractpmid34027837 doi101017 cjn2021118,0.0
mriguided laser interstitial thermal therapy using visualase system navigus frameless stereotaxy infant technical case report j neurosurg pediatr 2021 may 2114 doi 103171 202011peds20823 online ahead printabstractlaser interstitial thermal therapy litt increasingly used surgical option treatment epilepsy placement laser fibers relies stereotactic navigation cranial fixation pins addition laser fiber stabilized cranium ablation using cranial bolt assumes maturity skull therefore younger infants 2 years age traditionally considered candidates litt however litt appealing option patients familial epilepsy syndromes tuberous sclerosis complex tsc due multiplicity lesions likely need multiple procedures 4monthold infant tsc presented refractory focal seizures despite receiving escalating doses 5 antiepileptic medications electrographic clinical seizures occurred numerous times daily noninvasive evaluations including mri magnetoencephalography scalp eeg spect localized ictal onset left frontal cortical tuber premotor area paper authors report novel technique overcome challenges performing litt infant immature skull repurposing navigus biopsy skull mount stereotactic placement laser fiber using electromagneticbased navigation patient underwent successful ablation tuber remained seizure free 4 months postoperatively authors knowledge youngest reported patient undergo litt safe method described perform litt infant using commonly available tools without dedicated instrumentation beyond standard stereotactic navigation biopsy platform visualase systempmid34020419 doi103171 202011peds20823,0.0
sensitivity t1 t2weighted ratio detection cortical demyelination similar magnetization transfer ratio using postmortem mri mult scler 2021 may 2013524585211014760 doi 101177 13524585211014760 online ahead printabstractbackground detecting cortical demyelination using magnetic resonance imaging mri multiple sclerosis ms remains challenge magnetization transfer ratio mtr t1weighted t2weighted ratio t1t2r t2weighted t2w signal sensitive cortical demyelination accuracy unknownobjectives quantify sensitivity specificity accuracy postmortem t1t2r mtr t2w detecting cortical demyelinationmethods situ postmortem mris 9 patients used measure t1t2r mtr t2w along midline cortical gray matter classified normal abnormal mris coregistered compared hemispheric myelin staining sensitivity specificity accuracy t1t2r mtr t2w detecting cortical demyelination measuredresults mean age standard deviation death 647 + 137 years disease duration 238 + 105 years sensitivity 78 mtr 75 t1t2r 63 t2w specificity 46 t2w 13 t1t2r 29 mtr accuracy 71 t2w 39 mtr 42 t1t2r significant differences different mri measures cortical demyelination intracortical subpial lesion detectionconclusions although somewhat sensitive modest specificity conventional mri modalities cortical demyelination indicates influenced cortical changes demyelination improved acquisition postprocessing needed reliably measure cortical lesion loadpmid34014144 doi101177 13524585211014760,1.0
review clinical imaging findings tumefactive demyelination ajr j roentgenol 2021 may 19112 doi 102214 ajr2023226 online ahead printabstractobjective tumefactive demyelination mimics primary brain neoplasms imaging often necessitating brain biopsy article reviews literature clinical radiologic findings tumefactive demyelination various disease processes facilitate identification tumefactive demyelination imaging conclusion clinical radiologic findings must integrated distinguish tumefactive demyelinating lesions similarly appearing lesions imaging research immunopathogenesis tumefactive demyelination associated conditions will elucidate interrelationshippmid34010036 doi102214 ajr2023226,1.0
multiple sclerosis health resource utilization survey fortschr neurol psychiatr 2021 may 18 doi 101055 a14713636 online ahead printabstractbackground health economic studies valid reliable cost data essential reach meaningful conclusions case multiple sclerosis ms studies often based primary data underlying survey instruments published addition heterogeneous methods make comparability interpretation study results difficult standardize health economic studies ms multiple sclerosis health resource utilization survey mshrs developed validated published freely accessible formatresearch question review focuses mshrs report methodological background studies assessment cost illness well mshrsbased results costs disease dynamics people msmethods article based selective literature review mshrs well health economic aspects cost assessmentresults mshrs provides holistic assessment direct medical direct nonmedical indirect resource utilization within indirect costs considered absenteeism either short term sick leave long term disability pension also presenteeism refers impaired performance work resources valued societal opportunity cost best possible approximation first analyses based mshrs showed addition inpatient disease severity clinical course disease dynamics form relapses progression enormous socioeconomic implicationsconclusion valid cost data bring transparency economic consequences diseases addition clinical data cost data can used determine costeffectiveness thus reveal opportunities efficient patient care case ms freely accessible tool available cost assessmentspmid34005824 doi101055 a14713636,0.0
diseasemodifying agents multiple sclerosis risk reporting cancer disproportionality analysis using us food drug administration adverse event reporting system faers database br j clin pharmacol 2021 may 16 doi 101111 bcp14916 online ahead printabstractaim efficacy diseasemodifying therapies dmts patients multiple sclerosis ms established little known longterm safety cancerrisk dmts use remains unclear study aims investigate whether prescription dmts patients ms increases risk reporting cancermethods data fda adverseevent reporting system extracted 2004 2020 data cleaning crude adjusted reported odds ratios cror aror cancer calculated dmts interferonbeta1a reference drug sensitivity analyses investigated group reports multiple registered dmts effect indication restriction results using rest dmts referenceresults malignant tumors aror ci 95 cladribine 046 018095 dimethyl fumarate 030 027034 fingolimod 061 053070 glatiramer 050 043058 alemtuzumab 084 064108 interferonbeta1b 049 042056 natalizumab 036 034039 ocrelizumab 048 029074 peginterferonbeta1a 035 026048 siponimod 089 047154 teriflunomide 025 021030 adjusted age gender concomitant medications sensitivity analysis rest drugs used reference interferonbeta1a peginterferonbeta1a aror ci 95 260 247274 p0001 alemtuzumab 147 113188 p0003 conclusions safety signal increased cancerrisk detected among approved dmts although robust evidence needed potential safety signal detected sensitivity analysis concerning interferonbeta1a alemtuzumab requires evaluation robust evidencepmid33998034 doi101111 bcp14916,0.0
videoconferencing multiple sclerosis management stopgap stay tuned can j neurol sci 2021 may 17111 doi 101017 cjn2021113 online ahead printno abstractpmid33998416 doi101017 cjn2021113,0.0
bisphenol factor mosaic autoimmunity endocr metab immune disord drug targets 2021 may 13 doi 102174 1871530321666210516000042 online ahead printabstractthe population worldwide largely exposed bisphenol bpa commonly used plasticizer similar molecular structure endogenous estrogens therefore able influence physiological processes human body taking part pathophysiology various endocrinopathies well cardiovascular neurological oncological diseases bpa found affect immune system leading development autoimmunity allergies last decades prevalence autoimmune diseases significantly increased explained rising exposure population environmental factors bpa bpa found play role pathogenesis systemic autoimmune diseases also organspecific autoimmunity thyroid autoimmunity diabetes mellitus type 1 myocarditis inflammatory bowel disease multiple sclerosis encephalomyelitis etc results studies remain still controversial research neededpmid33992069 doi102174 1871530321666210516000042,0.0
social cognition executive functioning multiple sclerosis clusteranalytic approach j neuropsychol 2021 may 14 doi 101111 jnp12248 online ahead printabstractmultiple sclerosis ms associated deficits social cognition process underlying social interaction cognitive function however relationships executive impairment social cognition remain unclear ms previous studies exclusively focused group comparisons healthy controls patients ms treating latter homogeneous population variability socio neurocognitive profiles pathology therefore remains underexplored present study used cluster analytic approach explore heterogeneity executive social cognition skills ms total 106 patients ms compared 53 healthy matched controls executive eg working memory social cognition facial emotion recognition theory mind performances cluster analysis performed focusing ms sample explore presence differential patterns interaction executive social cognition difficulties links sociodemographic clinical cognitive variables identified three distinct functional profiles patients executive social cognition deficits cluster 1 patients difficulties facial emotion recognition theory mind lesser extent executive functioning cluster 2 patients executive functioning difficulties cluster 3 clinical characteristics disease duration disability fatigue differ clusters conclusions results suggest qualitative differences social cognition executive difficulties commonly found among patients ms replicated identification profiles clinical practice allow individualized rehabilitationpmid33989458 doi101111 jnp12248,0.0
toulousepiron cancellation test normative scores portuguese population appl neuropsychol adult 2021 may 1317 doi 101080 2327909520211918694 online ahead printabstractthe toulousepiron cancelation test tp classic psychometric tool assessment selective sustained attention processing speed visuoperceptual abilities commonly used neurological disorders epilepsy multiple sclerosis alzheimers disease encompasses two main indexes workefficiency dispersionindex di aim study provide normative scores tp sample portuguese healthy adults tp administered convenience sample 357 cognitivelydwelling subjects aged 45 86 years old following standard assessment protocol normative scores adjusted age education education main predictor tpwe r2 310 whereas influence age score lower r2 191 two variables explained 501 variance results regarding tpdi education also main predictor results r2 039 whereas age responsible r2 011 together explained 5 variance tpdi tp performances strongly influenced age education first study focused establishment normative data age 45 portuguese population allowing reliable assessment clinical research contextspmid33984245 doi101080 2327909520211918694,0.0
functional independence measure predicts outcome clean intermittent catheterization training patients multiple sclerosis ann phys rehabil med 2021 may 10101539 doi 101016 jrehab2021101539 online ahead printabstractbackground clean intermittent catheterization cic reference treatment urinary retention people multiple sclerosis pwms predicting patients use treatment based motor cognitive abilities crucialobjectives determine whether functional independence measure fim used assess degree disability can predict outcome cic training pwmsmethods pwms attending tertiary neurourology department 2011 2019 eligible cic included retrospective study level disability assessed fim occupational therapist success learning cic defined ability perform least 2 trials technique recorded end session continence nurse physiatrist association fim success learning cic assessed multivariable analysisresults included 395 patients mean sd age 498 120 years 70 women half patients relapsingremitting disease expanded disability status scale score 6 mean fim total motor cognitive scores 1080 142 759 123 321 37 respectively maximal scores 126 91 35 end session 87 patients successful learning cic adjustment potential confounding variables including age sex obesity edss score fim total motor cognitive subscores significantly associated success odds ratio 95 confidence interval 106 103108 105 103108 121 112132 respectively conclusions fim independent predictor successful cic training pwms 1point increase fim associated 6 increased odds successfully mastering cic technique widespread use fim help determine different cognitive motor objectives need improved cic teachingpmid33984538 doi101016 jrehab2021101539,0.0
lactoferrin mental health neuroredox regulation neuroprotective effects across bloodbrain barrier special reference neurocovid19 j diet suppl 2021 may 12135 doi 101080 1939021120211922567 online ahead printabstractoverall mental health depends part bloodbrain barrier regulates nutrient transfer inandout brain central nervous system lactoferrin innate metaltransport protein synthesized substantia nigra particularly dopaminergic neurons activated microglia vital brain physiology lactoferrin rapidly crosses bloodbrain barrier via receptormediated transcytosis accumulates brain capillary endothelial cells lactoferrin receptors additionally present glioma cells brain microvessels neurons regulator neuroredox microglial lactoferrin critical protection repair neurons healthy brain function iron imbalance oxidative stress common among patients neurodegenerative disorders parkinsons disease alzheimers disease dementia depression multiple sclerosis endogenous ironchelator lactoferrin prevents iron accumulation dopamine depletion parkinsons disease patients oral lactoferrin supplementation modulate pakt pten pathway reduce deposition ameliorate cognitive decline alzheimers disease novel lactoferrinbased nanotherapeutics emerged effective drugdelivery systems clinical management neurodegenerative disorders recent emergence coronavirus disease2019 covid19 pandemic initially considered respiratory illness demonstrated broader virulence spectrum ability cross bloodbrain barrier inflict plethora neuropathological manifestations brain neurocovid19 severe acute respiratory syndrome coronavirus 2 sarscov2 infections widely reported parkinsons disease alzheimers disease dementia multiple sclerosis patients aggravated clinical outcomes lactoferrin credited several neuroprotective benefits brain serve potential adjuvant clinical management neurocovid19pmid33977807 doi101080 1939021120211922567,1.0
effectiveness safety cladribine ms realworld experience two tertiary centres mult scler 2021 may 1213524585211012227 doi 101177 13524585211012227 online ahead printabstractbackground oral cladribine approved treatment relapsing multiple sclerosis ms yet realworld evidence regarding effectiveness safety remains scarceobjective evaluate efficacy safety outcomes ms patients following induction cladribinemethods evaluated prospective cohort cladribinetreated ms patients two tertiary centres germany relapses disability worsening occurrence new enlarging t2hyperintense magnetic resonance imaging mri lesions assessed well lymphocyte counts herpes virus infectionsresults among 270 patients treated cladribine observed profound reduction relapses new enlarging mri lesions treatment appeared efficacious especially patients without previous therapy following platform substances patients switching natalizumab prone reemerging disease activity among patients following dimethyl fumarate pretreatment severe lymphopenia common associated increased rates herpes virus manifestationsconclusion overall observed efficacy safety profile cladribine consistent data phase 3 clinical trial however patients switching natalizumab experienced suboptimal disease control beyond rebound activity following cessation natalizumab furthermore dimethyl fumarate pretreatment associated profound risk developing severe lymphopenia subsequent herpes virus infectionspmid33975489 doi101177 13524585211012227,0.0
clinical spectrum outcome uveomeningitis comprehensive analysis 110 cases ocul immunol inflamm 2021 may 1116 doi 101080 0927394820211898000 online ahead printabstractpurpose uveitis can associated meningitis uveomeningitis inflammation shared central nervous system aimed describe characteristics outcome uveomeningitismethods retrospectively analyzed 110 consecutive adult patients uveomeningitisresults main causes uveomeningitis vogtkoyanagiharada 31 syphilis 16 sarcoidosis 12 behets disease 7 multiple sclerosis 5 sixteen percent uveomeningitis remained undetermined origin compared etiologymatched uveitis without meningitis patients uveomeningitis younger frequent neurological manifestations frequent abnormal cerebral magnetic resonance imaging findings contrast ocular feature upon examination significantly associated presence meningitis patients uveomeningitis frequently treated immunosuppressants uveitis relapse systemic complications differ groupsconclusion uveomeningitis associated limited spectrum diseases meningitis seem impact ocular extraocular outcomes therefore lumbar puncture performed individual basis diagnostic workup uveitispmid33974484 doi101080 0927394820211898000,0.0
evaluation inflammatory acquired demyelinating syndromes children singlecenter experience acta neurol belg 2021 may 10 doi 101007 s13760021017034 online ahead printabstractto evaluate clinical neuroimaging features pediatric acquired demyelinating syndromes ads tertiary pediatric neurology clinic turkey children diagnosed subset ads 2013 2018 included retrospective cohort study fortytwo patients 21 female median followup period 30 months included median age patients disease onset 11 years range 1517 years common pediatric ads categories according international pediatric multiple sclerosis study group consensus classification criteria acute disseminated encephalomyelitis adem multiple sclerosis ms seen 15 patients followed clinically isolated syndrome cis n 11 neuromyelitis optica spectrum disorder nmosd n 1 first clinical event children adem significantly differed children affected ms cis terms following parameters median age onset 7 vs 135 145 years p 0001 encephalopathy 933 vs 0 0 p 0001 basal ganglia thalamus lesions 733 vs 91 91 p 0001 frequency seizure pleocytosis higher adem group ms group p 005 whereas oligoclonal bands p 0001 periventricular white matter lesions p 001 frequently observed ms patients rituximab used great success prevention relapses 3 patients nmosd n 1 ms n 1 adem followed recurrent optic neuritis n 1 results define longitudinal disease course various ads categories single referral center addition study compares various clinical laboratory neuroimaging features ads categoriespmid33973168 doi101007 s13760021017034,1.0
analysis frequency severity relapses multiple sclerosis patients treated cladribine tablets placebo clarity clarity extension studies mult scler 2021 may 1013524585211010294 doi 101177 13524585211010294 online ahead printabstractbackground clarity cladribine tablets treating multiple sclerosis orally study patients relapsingremitting multiple sclerosis treatment cladribine tablets 35 mg kg cladt significantly reduced annualised relapse rate arr versus placebo effect sustained clarity extension without treatmentobjective assess frequency severity relapses patients treated cladt versus placebo clarity 2 years evaluate durability effect patients received treatment 2 years clarity extensionmethods post hoc analysis arrs calculated qualifying relapses qualifying severe relapses ie requiring steroid treatment leading hospitalisation patients treated cladt n 433 placebo n 437 clarity cladt group received placebo clarity extension n 98 results month 6 year 1 year 2 patients receiving cladt significantly lower risk qualifying relapses p 00001 qualifying severe relapses p 0005 compared placebo effect sustained clarity extension without treatmentconclusion results show durable efficacy cladribine tablets 35 mg kg reducing frequency severity relapses patients relapsingremitting multiple sclerosisclarity nct00213135 clarity extension nct00641537pmid33969750 doi101177 13524585211010294,0.0
factors influence quality life patients multiple sclerosis saudi arabia disabil rehabil 2021 may 919 doi 101080 0963828820211919929 online ahead printabstractpurpose study factors may contribute quality life qol patients multiple sclerosis pwms saudi arabiamethods 175 pwms 71 age gender bmimatched healthy subjects participated crosssectional study qol studied multiple sclerosis quality life54 msqol54 depression disability fatigue measured beck depression inventoryii bdiii expanded disability status scale edss modified fatigue impact scale mfis respectively effects demographic clinical characteristics msqol54 studiedresults qol worse pwms better qol pwms linked male relapsingremitting ms lower bmi employed low disability minimal depression fatigued age disease duration marital status living status level education affect qol qol showed moderate strong correlation depression fatigue weak correlation edss depression fatigue strongest predictors qol predictors included gender bmi edssconclusions many factors seem influence qol pwms modifiable evaluation management factors may improve qol pwmsimplications rehabilitationassessment qol using proper tool part every pwms evaluationdepression fatigue main predictors qol pwms therefore attention paid evaluation managementsexual dysfunction pain assessed managed early course diseasepmid33966564 doi101080 0963828820211919929,0.0
mizaj assessment multiple sclerosis ms patients based persian medicine j complement integr med 2021 may 10 doi 101515 jcim20200428 online ahead printabstractobjectives increased incidence multiple sclerosis ms calls supporting complementary therapies field persian medicine pm specialists present various assumptions help patients mizaj temperament modification confirmation requires scientific evidence study aimed identifying mizaj ms patients comparing mizaj onset disease healthy peoplemethods fortytwo ms fiftyfour healthy subjects participated study case control groups general brain mizaj patients identified five pm specialists onset disease mojahedi mizaj questionnaire mmq completed two groups validity mmq assessed using mizaj diagnosis pm specialists gold standard ttest mcnemarbowker wilcoxon chisquare 2 tests used compare mizaj patients onset disease two groups p005 results sensitivity specificity mmq hotness 75 81 coldness 75 65 acceptable significant differences patients healthy subjects terms general mizaj general brain mizaj patients developing ms inclined coldness dryness although merely inclination general mizaj coldness significant p003 conclusions according results mizaj ms patients inclination toward coldness dryness also mmq can used validated scale identifying mizaj ms patients future studiespmid33964198 doi101515 jcim20200428,0.0
neurostructural neurophysiological correlates multiple sclerosis physical fatigue systematic review metaanalysis crosssectional studies neuropsychol rev 2021 may 7 doi 101007 s11065021095081 online ahead printabstractfatigue one debilitating symptoms people multiple sclerosis pwms consolidating diverse conflicting evidencebase systematic review metaanalysis aimed gain new insights neurobiology ms fatigue medline proquest cinahl web science databases grey literature searched using medical subject headings eligible studies compared neuroimaging neurophysiological data people experiencing high mshf versus low mslf levels perceived ms fatigue defined validated fatigue questionnaire cutpoints data available 66 studies 46 used metaanalyses neuroimaging studies revealed lower volumetric measures mshf versus mslf whole brain 2274 ml 95 ci 3772 776 ml p 0003 grey matter 1881 ml 95 ci 2960 803 ml p 0001 putamen 040 ml 95 ci 069 010 ml p 0008 acumbens 009 ml 95 ci 015 003 ml p 0003 higher volume t1weighted hypointense lesions 110 ml 95 ci 047 173 ml p 0001 neurophysiological data showed reduced lowerlimb maximum voluntary force production 1923 n 95 ci 3593 253 n p 002 attenuation upperlimb 577 95 ci861 293 p 00001 lowerlimb 216 95 ci424 007 p 004 skeletal muscle voluntary activation accompanied pronounced upperlimb fatigability 561 95 ci 957 165 p 0006 mshf versus mslf results suggest ms fatigue characterised greater corticosubcortical grey matter atrophy neural lesions accompanied neurophysiological decrements include reduced strength voluntary activation prospero registration prospero registration number crd42016017934pmid33961198 doi101007 s11065021095081,0.0
dendritic cell pik3c3 vps34 controls pathogenicity cns autoimmunity independently lc3associated phagocytosis autophagy 2021 may 7110 doi 101080 1554862720211922051 online ahead printabstractpik3c3 vps34 key player macroautophagy autophagy map1lc3 lc3associated phagocytosis lap play critical roles dendritic cell dc function study assessed contribution pik3c3 dc function experimental autoimmune encephalomyelitis eae animal model multiple sclerosis ms found pik3c3deficient dcs exhibit attenuated capacity reactivate encephalitogenic t cells central nervous system leading reduced incidence severity eae dcspecific pik3c3deficient mice additionally animals dcspecific deficiency rb1cc1 fip200 rubcn protected eae suggesting eae phenotype dcspecific pik3c3deficient mice due defective canonical autophagy rather lap collectively studies revealed critical role pik3c3 dc function pathogenicity cells eae important implications development immunotherapies autoimmune diseases mspmid33960279 doi101080 1554862720211922051,0.0
interplay cognitive bowel bladder function multiple sclerosis int neurourol j 2021 may 6 doi 105213 inj2040346173 online ahead printabstractpurpose evaluate prevalence bowel bladder dysfunction multiple sclerosis ms association cognitive impairmentmethods prospectively enrolled 150 ms patients patients administered symbol digit modality test sdmt filled neurogenic bowel dysfunction score nbds actionable bladder symptom screening tool absst association bowel bladder dysfunction cognitive function assessed hierarchical regression models using sdmt clinicdemographic features independent variables nbds absst score dependent variablesresults prevalence bowel bladder deficit 447 26 patients 173 suffering bowel deficits 60 patients 40 bladder deficits total nbds absst correlated sdmt coeff 010 p0001 coeff 003 p004 respectively correction demographic features physical disabilityconclusions bowel bladder disorders common ms associated physical cognitive disability burden sdmt embedded routine clinical assessment lower score may warrant investigating bowel bladder dysfunction due strong interplaypmid33957715 doi105213 inj2040346173,0.0
nacetylcysteine protects cuprizoneinduced demyelination histological immunohistochemical study folia morphol warsz 2021 may 6 doi 105603 fma20210044 online ahead printabstractmyelination sequential process tightly controlled number intrinsic extrinsic factors cns disease neuronal myelin sheath damaged referred demyelinating disease present work designed study histopathological ultrastructural immunohistochemical changes rat brain mainly corpus callosum cc following oral administration cuprizone cpz role nacetylcysteine nac reducing changes demyelination induced cpz administration short 4ws long 8ws periods nac given concomitantly sequentially similar periods spontaneous recovery cessation cpz followed medication also investigated end experimental period cerebral hemispheres extracted prepared light electron microscopic examination immunohistochemical study obtained results showed direct proportion duration cpz administration severity demyelination coadministration cpz nac fair protective impact stronger sequential administration two drugs incomplete spontaneous remyelination observed cessation cpz evident short long period group indicating cpz administration prolonged remyelination delayed light results concluded nac neuroprotective effects potential novel therapeutic approach treatment demyelinating diseases multiple sclerosis however treatment begin soon disease manifestspmid33954959 doi105603 fma20210044,1.0
aggregation autoimmunity extended families people autoimmune addison#39 s disease intern med j 2021 may 5 doi 101111 imj15337 online ahead printabstractbackground autoimmunity accounts 90 cases primary adrenal insufficiency addisons disease ad affected persons present significant cooccurrence autoimmune conditions hence clustering autoimmunity also predicted among relativesaims aim study evaluate burden autoimmunity families people admethods 116 individuals ad surveyed occurrence 23 autoimmune diseases among relativesresults 741 persons ad reported least one relative autoimmune disorder 257 cases diagnosed 221 relatives hashimotos thyroiditis found 100 individuals followed graves disease vitiligo 25 24 relatives respectively type 1 diabetes diagnosed 23 relatives psoriasis 15 rheumatoid arthritis 12 pernicious anaemia 11 multiple sclerosis 8 premature menopause 8 women ad found 7 relatives alopecia 6 celiac disease 5 conditions rare significant correlation noticed number autoimmune conditions ad proband number affected relatives p 0031 664 people ad firstdegree relative suffering autoimmunity autoimmune conditions frequent among females sisters p 0001 mothers p 0002 grandmothers p 0002 conclusions considerable prevalence autoimmune conditions relatives persons ad confirms substantial risk autoimmunity especially females relatives patients affected multiplex autoimmunity data corroborate recommendation active screening autoimmune disorders particularly thyroid disease among ad family members article protected copyright rights reservedpmid33955139 doi101111 imj15337,0.0
staging stratifying cognitive dysfunction multiple sclerosis mult scler 2021 may 613524585211011390 doi 101177 13524585211011390 online ahead printabstractbackground sequence cognitive domains become impaired multiple sclerosis ms yet formally demonstrated unclear whether processing speed dysfunction temporally precedes cognitive impairments memory executive functionobjective determine order different cognitive domains become impaired ms validate findings using clinical vocational outcomesmethods longitudinal sample 1073 ms patients 306 healthy controls measured performance multiple consensusstandard neurocognitive tests used eventbased staging approach model sequence cognitive domains become impaired linear logistic mixedeffects models used explore associations stages impairment neurological disability employment statusresults model suggested order impairments follows processing speed visual learning verbal learning working memory attention executive function stage cognitive impairment predicted greater neurological disability 016 se 002 p 0001 probability unemployment 114 se 0001 p 0001conclusion first study introduce cognitive staging stratification system ms findings underscore importance using symbol digit modalities test routine screening cognitive impairment memory testing assess patients later disease evolutionpmid33951975 doi101177 13524585211011390,0.0
aberrant immunoglobulin g glycosylation multiple sclerosis j neuroimmune pharmacol 2021 may 3 doi 101007 s11481021099961 online ahead printabstracta hallmark inflammatory response multiple sclerosis ms presence intrathecal immunoglobulin g igg antibodies oligoclonal bands ocbs biological activity iggs modulated changes glycosylation using multiple immunoassays common lectins sialylation galactosylation investigated levels igg glycosylation 28 ms 37 control sera well paired csf serum demonstrated presence significantly lower levels igg sialylation ms csf compared paired serum showed ms correlation sialylated igg total igg antibodies sialylated igg csf serum elisa native igg antibodies showed significantly higher levels sialylated galactosylated igg ms compared neurological disorders normal healthy controls conclude lower levels sialylated intrathecal igg higher levels serum igg galactosylation ms may play significant role disease pathogenesis unique igg glycosylation profiles suggest complexed nature igg antibodies may influence effector functions mspmid33942224 doi101007 s11481021099961,0.0
cognitive assessment multiple sclerosis clinical care qualitative evaluation stakeholder perceptions preferences neuropsychol rehabil 2021 may 3119 doi 101080 0960201120211899942 online ahead printabstractthere growing consensus cognitive assessments form part routine clinical care multiple sclerosis ms however remains unclear assessments preferred stakeholders including people ms family members charity volunteers clinicians healthcare commissioners contexts formats therefore aim study collect synthesize stakeholders perceptions assessments acceptable feasible routine administration uk healthcare systemwe interviewed 44 stakeholders held one focus group n 5 asked stakeholders experience cognitive impairment assessment views cognitive assessment implemented within routine clinical careusing framework analysis summarized three themes current cognitive screening situation suitability commonly used assessments feasibility aspects including modality location testing participants acknowledged cognitive impairment significant impact quality life assessment monitoring routinely performed clinics barriers enablers described participants reported brief routine screening tests symbol substitution acceptable electronic selfadministration cognitive screening beneficial minimizing clinic attendance staff timepmid33941045 doi101080 0960201120211899942,0.0
temporal trends incidence prevalence multiple sclerosis razavi khorasan province northeast iran neurol sci 2021 may 3 doi 101007 s10072021052805 online ahead printabstractobjectives prevalence multiple sclerosis ms persian gulf countries significantly increasing past decades study conducted investigating prevalence incidence ms northeast iran khorasan razavi province methods crosssectional study conducted 1 january 1988 23 september 2018 patients clinically definite diagnosis ms according mcdonald criteria 2005 mri along medical diagnosis recorded khorasan ms society considered calculation crude agestandardized prevalence incidence rates ms periodic incidence rates calculated based year onset ms also calculated gender ratios prevalence incidence ratesresults mean agestandardized prevalence incidence rates ms khorasan razavi 869 95 ci 805941 per 100 000 399 95 ci 339474 males 1349 95 ci 12371476 females agestandardized prevalence 4887 95 ci 48374935 per 100 000 2247 95 ci 22012293 males 7565 95 ci 74807651 females also mean incidence prevalence mashhad county capital province 1138 5909 per 100 000 populations respectively female male ratio 333 age groupsconclusion results showed region highrisk area ms like central region iran results revealed prevalence incidence ms study area increased recent decades sharp slopepmid33939041 doi101007 s10072021052805,0.0
role micrornas aptamers neuroinflammation neurodegenerative disorders cell mol neurobiol 2021 may 1 doi 101007 s10571021010934 online ahead printabstractexploring micrornas aptamers therapeutic role biological drugs expanded horizon applicability various human diseases explicitly targeting genetic materials rnabased therapeutics widely explored treatment diagnosis multiple diseases including neurodegenerative disorders ndd latter includes microrna aptamers ribozymes small interfering rnas sirnas control gene expression mainly transcriptional strata one rna transcript translates different protein types hence therapies targeted transcriptional sphere may prominent extensive effects alternative therapeutics unlike conventional gene therapy rnas upon delivery can either altogether abolish alter synthesis protein interest therefore regulating activities controlled diverse manner ndds like alzheimers disease parkinsons disease huntingtons disease multiple sclerosis prion disease others characterized deposition misfolded protein amyloid tau synuclein huntingtin prion proteins neuroinflammation one perquisites neurodegeneration induced neurodegenerative pathogenesis review discuss micrornas aptamers role two different rnabased approaches unique ability regulate protein production transcription level hence offering many advantages biologicals microrna acts either alleviating malfunctioning rna expression working replacement lost microrna contrary aptamer act chemical antibody forms aptamertarget complexpmid33934227 doi101007 s10571021010934,0.0
autoantibody predictors gastrointestinal symptoms systemic sclerosis rheumatology oxford 2021 apr 28keab395 doi 101093 rheumatology keab395 online ahead printabstractobjectives assess prevalence burden systemic sclerosis ssc related gastrointestinal dysfunction sscgi evaluate associations demographic clinical serological characteristicsmethods patients completed ucla sctc git 20 questionnaire sscgi disease assess burden gi disease across multiple functional psychological domains questionnaire scores assessed using nonparametric quantile regression analysesresults cohort included 526 patients ssc typical distribution diseaseassociated autoantibodies aca ara ata pmscl u1rnp u3rnp demonstrated associations hallmark antibodies domainspecific burden gi disease particular aca ara enanegative demonstrated increased sscgi disease burden whilst pmscl conferred relative protection distributional analysis associations autoantibodies particularly marked highest burden gi diseaseconclusion significant burden sscgi disease patients ssc reflux bloating symptoms prominent ssc hallmark antibodies may predict increased risk sscgi disease particular aca ara whilst pmscl may protectivepmid33909895 doi101093 rheumatology keab395,0.0
effect anxiety level social support given multiple sclerosis patients perspect psychiatr care 2021 apr 28 doi 101111 ppc12807 online ahead printabstractpurpose descriptive study aiming determining effect anxiety level social support given multiple sclerosis ms patientsdesign methods study conducted 123 ms patients data collected multidimensional scale perceived social support mspss hamilton anxiety rating scale hama results multidimensional scale perceived social support total score average 5718 185 hama total score average 2033 1042 negative weak significant relationship found mspss total score average hama total score subdimensionspractice implications ms nurses plan anxiety management accordingly giving holistic care evaluating social support mechanismspmid33908627 doi101111 ppc12807,0.0
effects supervised versus home pilatesbased core stability training lower extremity muscle strength postural sway people multiple sclerosis mult scler 2021 apr 2813524585211012202 doi 101177 13524585211012202 online ahead printabstractbackground pilatesbased core stability training pbcst controlled form exercise may improve transmission torque upper extremities trunk lower extremities enabling core muscles activate effectivelyobjectives aim study investigate effects pbcst given supervised homebased lower extremity strength postural control multiple sclerosismethods fifty individuals enrolled randomly allocated two groups primary outcome measures knee muscle strength postural sway different conditions supervised group received pbcst 2 days per week 8 weeks clinic group performed pbcst home exercises progressed every 2 weeks groupsresults groups supervised group mostly superior home group p 005 significant improvement noted parameters groups except subparameters postural sway home pbcst p 005 conclusions supervised pbcst determined effective home pbcst improving strength postural control core stability physical capacity fatigue although supervised training primary choice home training can recommended patients limitations attending supervised sessionspmid33908294 doi101177 13524585211012202,0.0
effects tactile stimulation sensory motor cognitive function people multiple sclerosis clin neurol neurosurg 2021 apr 20 205106643 doi 101016 jclineuro2021106643 online ahead printabstractobjective multiple sclerosis ms chronic inflammatory neurodegenerative disease causes demyelination brain spinal cord repetitive sensory stimulation rss can enhance sensory perception motor function improve inappropriate synaptic connections adaptable malformations increase cognitive function purpose study specify effect rss sensory motor cognitive function people msmethods rss applied 50 people ms study following tests used twopoint discrimination 9hole peg test 9hpt box block test bbt hand mental rotation hmr paced auditory serial addition test pasat symbol digit modalities test sdmt tests performed interventionresults results study showed significant difference stimulation intervention control groups twopoint discrimination threshold groups 0001 bbt score groups p 0001 9hpt score groups p 0001 hmr ability reaction time groups p 0003 accuracy rate intervention p 0004 control p 0001 pasat score intervention p 0001 control p 0012 sdmt score intervention p 0008 control p 0001 statistical difference observed two groups intervention terms mentioned variables p 005 conclusion application 30 min rss right index finger people ms improve twopoint discrimination threshold manual dexterity addition intervention improve cognitive functionpmid33906001 doi101016 jclineuro2021106643,1.0
subclinical atherosclerosis patients relapsingremitting multiple sclerosis wien klin wochenschr 2021 apr 26 doi 101007 s00508021018627 online ahead printabstractbackground multiple sclerosis inflammatory disorder central nervous system inflammation may create high susceptibility subclinical atherosclerosis purpose study compare subclinical atherosclerosis role inflammatory cytokines group patients relapsingremitting multiple sclerosis rrms healthy controls matched age sexmethods study group consisted 112 nondiabetic nonhypertensive rrms patients treated disease modifying drugs dmd control group composed 51 healthy subjects common carotid artery cca intima media thickness imt investigated serum levels risk factors atherosclerosis inflammatory cytokines also determinedresults mean cca imt 0572 0131 mm vs 0571 0114 mm differ p 005 patients controls rrms patients cca imt significantly correlated serum interleukin 6 il6 p 0027 highsensitivity creactive protein hscrp p 0027 cystatin c p 00005 glucose p 0031 cholesterol p 0008 ldl p 0021 erythrocyte sedimentation rate p 0001 triglyceride p 0018 level fitted generalized linear models order assess relationship cca imt il6 adjustment sex age obtained results showed adjusted age p 0001 sex p 0048 il6 serum levels statistically significantly p 0009 predict cca imt rrms groupconclusion findings present study suggest treated dmd rrms might independent risk factor early atherosclerosis presenting arterial wall thickening however results suggest significant association il6 serum levels cca imt rrms grouppmid33903956 doi101007 s00508021018627,0.0
systematic assessment medical diagnoses preceding first diagnosis multiple sclerosis neurology 2021 apr 26101212 wnl0000000000012074 doi 101212 wnl0000000000012074 online ahead printabstractobjective explore occurrence diseases symptoms five years prior diagnosis patients multiple sclerosis ms casecontrol studymethods using ambulatory claims data systematically assessed differences occurrence diseases symptoms five years prior first diagnosis patients ms n10 262 compared patients two autoimmune diseases crohns disease n15 502 psoriasis n98 432 individuals without diseases n73 430 results fortythree icd10 codes recorded frequently patients ms diagnosis compared controls without autoimmune disease many findings confirmed comparison control groups high proportion icd10 codes represent symptoms suggestive demyelinating events neurological diagnoses sensitivity analysis excluding patients recordings prior first diagnosis association remained significant seven icd10 codes associated lower odds ratios ms four represented upper respiratory tract infections relations ms even pronounced sensitivity analysisconclusions analyses suggest patients ms frequently diagnosed first demyelinating event often years later symptoms physician encounters ms diagnosis seem related already ongoing disease rather prodrome observed association upper respiratory tract infections lower ors ms diagnosis suggests link protection infection ms however needs validated investigatedpmid33903190 doi101212 wnl0000000000012074,1.0
early diagnosis multiple sclerosis evidence missed opportunity neurology 2021 apr 26101212 wnl0000000000012087 doi 101212 wnl0000000000012087 online ahead printno abstractpmid33903189 doi101212 wnl0000000000012087,0.0
quality sleep fatigue patients relapsingremitting multiple sclerosis coronavirus disease2019 pandemic clin neurol neurosurg 2021 apr 14 205106640 doi 101016 jclineuro2021106640 online ahead printabstractbjective sleep disturbances fatigue frequent symptoms multiple sclerosis patients aim assess quality sleep qos fatigue patients relapsingremitting multiple sclerosis rrms coronavirus disease2019 covid19 pandemicmethods study included 67 patients rrms 85 healthy control subjects rrms patients tested first half 2019 retested april may 2020 covid19 pandemic collected sociodemographic clinical data also used following questionnaires pittsburgh sleep quality index psqi fatigue severity scale fss multiple sclerosis quality life54 instrument msqol54 results fss score psqi global score significantly higher patients rrms control group p 001 noticed statistically significant difference results obtained year ago results covid19 pandemic psqi global score p 001 subscores higher disability status independent predictor worse psqi scoresconclusion covid19 outbreak worse qos noticed rrms patients healthy individuals also qos rrms patients affected covid19 pandemic regular circumstances high levels sleep disturbance fatigue rrms patients correlates worse life quality female gender lower educational level partner status results present study provide evidence support regular screening monitoring fatigue qos patient population especially pandemic statespmid33901751 doi101016 jclineuro2021106640,0.0
embracing resilience multiple sclerosis new perspective covid19 pandemic psychol health med 2021 apr 2519 doi 101080 1354850620211916964 online ahead printabstractcoronavirus disease 2019 covid19 resulted several psychological consequences past epidemiological experiences already showed deep albeit heterogeneous psychological repercussions pandemics nevertheless little known covid19 outbreak possible strategies boosting resilience patients chronic diseases multiple sclerosis ms therefore designed study aiming assess changes mental distress covid19 outbreak patients ms identifyfactors contributing resiliences developmentwe enrolled 106 patients 69 relapsingremitting 20 secondaryprogressive 17 primaryprogressive whose neuropsychological assessment covid19 pandemic 1 january 20191 march 2020 available consisted brief international cognitive assessment ms bicams hospital anxiety depression scale hads patientreported ms neuropsychological screening questionnaire msnqp patients retested italian lockdown online survey comprehensive sociodemographic information hads selfrating scale msnqp questionnaire finally connordavidson resilience selfrating scale cdrisc 25 order evaluate resilienceno significant changes hads msnqp scores detected covid19 pandemic population though preexisting lower hads msnqp scores demographic disease treatmentrelated elements found significantly p 00001 independently associated better resilience attitudepmid33899615 doi101080 1354850620211916964,0.0
serum contactin1 biomarker longterm disease progression natalizumabtreated multiple sclerosis mult scler 2021 apr 2313524585211010097 doi 101177 13524585211010097 online ahead printabstractbackground natalizumab treatment provides model noninflammationinduced disease progression multiple sclerosis ms objective study serum contactin1 scntn1 novel biomarker disease progression natalizumabtreated relapsingremitting ms rrms patientsmethods eightynine natalizumabtreated rrms patients minimum followup 3 years included scntn1 analyzed baseline natalizumab initiation 3 12 24 months m last followup median 52 years compared 222 healthy controls hc 15 primary progressive ms patients ppms results compared patients progressive stable improved disability according edssplus criteriaresults median scntn1 levels ng ml rrms baseline 107 3m 97 12m 104 24m 108 last followup 97 significantly lower compared hc 125 p 0001 observed 48 patients showed progression followup 11 improved 40 remained stable scntn1 levels significantly lower progressors baseline 12m compared nonprogressors 1 ng ml decrease baseline scntn1 consistent odds ratio 123 95 confidence interval 104145 p 0017 progression followupconclusion lower baseline scntn1 concentrations associated longterm disability progression natalizumab treatment making possible bloodbased prognostic biomarker rrmspmid33890520 doi101177 13524585211010097,0.0
effect continuous positive airway pressure treatment obstructive sleep apneahypopnea multiple sclerosis randomized doubleblind placebocontrolled trial samspap study mult scler 2021 apr 2313524585211010390 doi 101177 13524585211010390 online ahead printabstractobjective aim study evaluate effect continuous positive airway pressure cpap treatment fatigue severity scale fss preplanned primary outcome another fatigue measure sleep quality somnolence pain disability quality life multiple sclerosis ms patients obstructive sleep apneahypopnea osah methods randomized doubleblind trial nct01746342 ms patients fatigue poor subjective sleep quality osah apneahypopnea index 15 events per hour sleep without severe osah apneahypopnea index 30 4 oxygen desaturation index 15 events hour severe somnolence randomized fixed cpap sham cpap 6 months outcome assessments performed 3 6 monthsresults 49 randomized patients 34 completed protocol among completers fss improve cpap compared sham 6 months fss tended improve p 009 sleepiness epworth sleepiness scale improved significantly p 003 3 months cpap compared sham improvements cpap either study evaluationconclusion nonsevere osah patients cpap significantly improve primary outcome fss change 6 months secondary analyses found trend improved fss significant reduction somnolence cpap 3 monthspmid33890515 doi101177 13524585211010390,0.0
mir124 promising therapeutic target central nervous system injuries diseases cell mol neurobiol 2021 apr 22 doi 101007 s10571021010916 online ahead printabstractcentral nervous system injuries diseases ischemic stroke spinal cord injury neurodegenerative diseases glioblastoma multiple sclerosis resulting neuroinflammation often lead death longterm disability micrornas small noncoding singlestranded rnas regulate posttranscriptional gene expression physiological pathological cellular processes including central nervous system injuries disorders studies mir124 one abundant micrornas central nervous system shown dysregulation related occurrence development pathology within central nervous system herein review molecular regulatory functions underlying mechanisms effective delivery methods mir124 central nervous system involved pathological conditions review also provides novel insights therapeutic target potential mir124 treatment human central nervous system injuries diseasespmid33886036 doi101007 s10571021010916,0.0
agathisflavone modifies microglial activation state myelination organotypic cerebellar slices culture j neuroimmune pharmacol 2021 apr 21 doi 101007 s11481021099916 online ahead printabstractoligodendrocytes produce myelin critical rapid neuronal transmission central nervous system cns disruption myelin devastating effects cns function demyelinating disease multiple sclerosis ms microglia endogenous immune cells cns play central role demyelination repair need new potential therapies regulate myelination microglia promote repair agathisflavone fab nontoxic flavonoid known antiinflammatory neuroprotective properties examined effects fab 550 m myelination microglia organotypic cerebellar slices prepared p10p12 sox10egfp plp1dsred transgenic mice immunofluorescence labeling myelin basic protein mbp neurofilament nf demonstrates fab significantly increased proportion mbp + nf + axons affect overall number oligodendroglia axons expression oligodendroglial proteins cnpase mbp fab known phytoestrogen blockade estrogen receptors er indicated myelination promoting effects fab mediated er examination microglial responses iba1 immunohistochemistry demonstrated fab markedly altered microglial morphology characterized smaller somata reduced branching processes consistent decreased state activation increased iba1 protein expression results provide evidence fab increases extent axonal coverage mbp immunopositive oligodendroglial processes modulatory effect upon microglial cells important therapeutic strategies multiple neuropathologiespmid33881709 doi101007 s11481021099916,1.0
beyond ajr quot longterm evolution multiple sclerosis iron rim lesions 7 t mriquot ajr j roentgenol 2021 apr 21 doi 102214 ajr2125953 online ahead printno abstractpmid33881902 doi102214 ajr2125953,0.0
central vein sign radiographic features distinguishing myelin oligodendrocyte glycoprotein antibody disease multiple sclerosis aquaporin4 antibodypositive neuromyelitis optica mult scler 2021 apr 1913524585211007086 doi 101177 13524585211007086 online ahead printabstractbackground myelin oligodendrocyte glycoprotein antibody disease mogad can radiographically mimic multiple sclerosis ms aquaporin4 aqp4 antibodypositive neuromyelitis optica spectrum disorder nmosd central vein sign cvs prevalence yet wellestablished mogadobjective characterize magnetic resonance imaging mri appearance cvs prevalence mogad patients comparison matched cohorts ms aqp4+ nmosdmethods clinical mris 26 mogad patients compared matched cohorts ms aqp4+ nmosd brain mris assessed involvement within predefined regions interest cvs assessed overlaying fluidattenuated inversion recovery flair susceptibilityweighted sequences topographic analyses performed spinal cord orbital mris availableresults mogad patients fewer brain lesions average cvs+ rate 121 compared 444 ms patients p 00008 mogad spinal cord optic nerve involvement lengthier ms 58 vs 10 vertebral segments p 0020 30 vs 05 cm p 00001 mogad patients tended bilateral anterior optic nerve pathology perineural contrast enhancement contrasting posterior optic nerve involvement nmosdconclusion cvs+ rate longer segments involvement spinal cord optic nerve can differentiate mogad ms discriminate well mogad aqp4+ nmosdpmid33870786 doi101177 13524585211007086,1.0
disability multiple sclerosis related thalamic connectivity cortical network atrophy mult scler 2021 apr 1913524585211008743 doi 101177 13524585211008743 online ahead printabstractbackground thalamic atrophy proposed major predictor disability progression multiple sclerosis ms thalamic function remains understudiedobjectives study thalamic functional connectivity fc related disability thalamic cortical network atrophy two large ms cohortsmethods structural restingstate functional magnetic resonance imaging fmri obtained 673 subjects amsterdam ms n 332 healthy controls hc n 96 graz ms n 180 hc n 65 comparable protocols including disability measurements ms expanded disability status scale edss atrophy measured thalamus seven wellrecognized restingstate networks static dynamic thalamic fc networks correlated disability significant correlates included backward multivariate regression modelresults disability strongly related adjusted r2 057 p 0001 higher age progressive phenotype thalamic atrophy increased static thalamic fc sensorimotor network smn static thalamussmn fc significantly higher patients high disability edss 4 related network atrophy thalamic atrophy lesion volumesconclusion severity disability ms related increased static thalamic fc smn thalamic fc changes related cortical network atrophy thalamic atrophypmid33870779 doi101177 13524585211008743,0.0
csf chitinase 3like 1 associated iron rims patients first demyelinating event mult scler 2021 apr 1913524585211010082 doi 101177 13524585211010082 online ahead printabstractbackground chronic active lesions iron rims prognostic implications patients multiple sclerosisobjective assess relationship iron rims levels chitinase 3like 1 chi3l1 neurofilament light chain nfl glial fibrillary acidic protein gfap patients first demyelinating eventmethods iron rims identified using 3t susceptibilityweighted imaging serum nfl gfap levels measured singlemolecule array assays csf cerebrospinal fluid chi3l1 levels measured enzymelinked immunosorbent assay elisa results sixtyone patients included study presence iron rims associated higher t2 lesion volume higher number gadoliniumenhancing lesions univariable analysis 2 iron rims vs 0 associated increased csf chi3l1 levels 141 95 confidence interval ci 110179 p 001 serum nfl levels 230 95 ci 147360 p 001 multivariable analysis however csf chi3l1 levels remained significantly associated presence iron rim lesions 145 95 ci 111190 p 001 presence 2 iron rims associated increased serum gfap levels univariable multivariable analysesconclusion findings support important contribution activated microglia macrophages pathophysiology chronic active lesions iron rims patients first demyelinating eventpmid33870790 doi101177 13524585211010082,1.0
cognitive performance patients multiple sclerosis optic neuritis presentation j neuroophthalmol 2021 apr 14 doi 101097 wno0000000000001245 online ahead printabstractbackground cognitive dysfunction common among patients multiple sclerosis ms effect coexisting optic neuritis first presentation multiple sclerosis course cognitive decline unknown purpose study assess whether presentation effect progression cognitive decline msmethods historical cohort study retrospectively compared cognitive performance patients relapsingremitting ms without time ms diagnosis subjects included cognitive test results available baseline least 36 months presentation grouped based presence mson absence msnonon optic neuritis presentationresults one hundred seventy consecutive subjects ms found suitable 12 malefemale ratio mean age diagnosis 330 109 years fortysix patients 271 presented significant differences found cognitive performance onset 2 groups groups similar followup duration prevalence cognitive decline general score significantly higher mson group compared msnonon group 65 vs 0 respectively p 0001 well attention 87 vs 16 p 0046 executive function 174 vs 24 p 0001 domainsconclusions optic neuritis presentation ms associated higher prevalence cognitive decline time potential benefit early intervention prevent cognitive decline may warrantedpmid33870943 doi101097 wno0000000000001245,0.0
current status neuroprotective neuroregenerative strategies multiple sclerosis systematic review mult scler 2021 apr 1913524585211008760 doi 101177 13524585211008760 online ahead printabstractbackground immunemediated demyelination consequent degeneration oligodendrocytes axons hallmark features multiple sclerosis ms remyelination declines progressive ms causing permanent axonal loss irreversible disabilities strategies aimed enhancing remyelination critical attenuate disease progressionobjective systematically reviewed recent advances neuroprotective regenerative therapies ms covering preclinical clinical studiesmethods searched three biomedical databases using defined keywords two authors independently reviewed articles inclusion based prespecified criteria data extracted study assessed risk biasresults search identified 7351 studies 2014 2020 221 met defined criteria studies reported 262 interventions wherein 92 evaluated animal models interventions comprised protein rna lipid cellular biologics small molecules inorganic compounds dietary physiological interventions small molecules highly represented strategy followed antibody therapies stem cell transplantationconclusion significant strides made develop regenerative treatments ms current evidence illustrates skewed representation types strategies advance clinical trials examination thus required address current barriers implementing experimental treatments clinical settingspmid33870797 doi101177 13524585211008760,1.0
downregulation mir125a5p mir2185p peripheral blood mononuclear cells patients relapsingremitting multiple sclerosis immunol invest 2021 apr 19113 doi 101080 0882013920211909616 online ahead printabstractmultiple sclerosis ms chronic neuroinflammatory disease brain spinal cord evidences demonstrated micrornas mirnas involved pathological process ms may confer valuable diagnostic biomarker disease diagnosis prognosis treatment hence assessed expression pattern mir125a5p mir2185p peripheral blood mononuclear cells pbmcs subjects relapsingremitting multiple sclerosis rrms recruited 50 rrms patients 50 age sexmatched healthy control subjects pbmcs isolated peripheral blood samples rna content extracted cdna synthesized finally expression level mirnas determined using quantitative realtime pcr data indicate significant downregulation mir125a5p mir2185p rrms patients compared healthy controls p 0001 levels mirnas significantly downregulated agedependent manner compared consistent healthy control groups 3040 years old p 0001 expression level mir2185p significantly changed female patients female group p 0001 male group p 12 receiver operating characteristic roc curve data indicated expression levels mirnas able discriminate rrms patients healthy subjects p 05 moreover bioinformatic enrichment analysis revealed target genes mirnas cardinal roles regulation key biological pathways involved clinical course pathogenesis ms collectively results suggested mir125a5p mir2185p play role rrms pathogenesis age sexdependent expression pattern patientspmid33866949 doi101080 0882013920211909616,0.0
pituitary metastasis unveiling lung adenocarcinoma endocrinol diabetes metab case rep 2021 feb 26 2021edm200211 doi 101530 edm200211 online ahead printabstractsummary pituitary metastasis pm can initial presentation otherwise unknown malignancy pm clinical radiological pathognomonic features diagnosis challenging authors describe case symptomatic pm revealed primary lung adenocarcinoma 62yearold woman multiple sclerosis history malignancy incidentally presented diffusely enlarged homogeneously enhancing pituitary gland associated stalk enlargement clinical biochemical evaluation revealed anterior hypopituitarism diabetes insipidus hypophysitis considered likely diagnosis however rapid visual deterioration pituitary growth raised suspicion metastatic involvement search systemic malignancy performed ct revealed lung mass proved lung adenocarcinoma accordingly patient started immunotherapy resection pituitary lesion performed histopathology analysis revealed metastatic lung adenocarcinoma following surgery patient underwent radiotherapy 2 years pm detection patient shows clinically relevant response antineoplastic therapy evidence pm recurrencelearning points although rare metastatic involvement pituitary gland reported increasing frequency last decades pituitary metastasis can initial presentation otherwise unknown malignancy considered differential diagnosis pituitary lesions irrespective history malignancy sudden onset rapid progression visual endocrine dysfunction pituitary lesion strongly raise suspicion metastatic disease mri features pituitary metastasis can overlap pituitary lesions including hypophysitis however rapid pituitary growth highly suggestive metastatic disease survival pituitary metastasis detection improved time encouraging individualized interventions directed metastasis improve quality life increase survivalpmid33865234 doi101530 edm200211,0.0
central amygdala inflammation drives pain hypersensitivity attenuates morphine analgesia experimental autoimmune encephalomyelitis pain 2021 apr 9 doi 101097 jpain0000000000002307 online ahead printabstractchronic pain highly prevalent symptom associated autoimmune disorder multiple sclerosis ms central nucleus amygdala plays critical role pain processing modulation neuropathic pain alters nociceptive signaling central amygdala contributing pain chronicity opioid tolerance demonstrate activated microglia within central amygdala disrupt nociceptive sensory processing contribute pain hypersensitivity experimental autoimmune encephalomyelitis eae frequently used animal model ms male female mice eae exhibited differences microglial morphology central amygdala associated heat hyperalgesia impaired morphine reward reduced morphine antinociception females eae animals displayed lack morphineevoked activity cells expressing somatostatin within central amygdala drive antinociception induction focal microglial activation nave mice via injection lipopolysaccharide central amygdala produced loss morphine analgesia females similar observed eae animals data indicate activated microglia within central amygdala may contribute sexually dimorphic effects morphine may drive neuronal adaptations lead pain hypersensitivity eae results provide possible mechanism underlying decreased efficacy opioid analgesics management msrelated pain identifying microglial activation potential therapeutic target pain symptoms patient populationpmid33863858 doi101097 jpain0000000000002307,0.0
aging multiple sclerosis longitudinal study physical function mental health memory two cohorts us women mult scler 2021 apr 1613524585211007739 doi 101177 13524585211007739 online ahead printabstractbackground unknown individuals multiple sclerosis ms age compared unaffected peersobjectives objective study describe impact ms health functioning aging womenmethods used 10item physical functioning scale pf10 scores short form36 sf36 indicators general physical mental health memory collected repeatedly 25 years selfadministered questionnaires among participants nurses health study n 121 700 recruited ages 3055 nurses health study ii n 116 429 recruited ages 2542 compare women ms n 733 unaffected peers health disability describe quantify burden aging msresults women ms consistently lower pf10 0917 standard deviations greater overall variability unaffected women pf10scores gradually decreased increasing age groups ms cases declined 34 times faster midlife decline similar old age physical function score 45yearold women ms comparable 75yearold unaffected women 70yearold women ms scored similarly 85yearold unaffected women ms cases also reported worse health disability throughout adulthood indicatorsconclusion agerelated decline physical health accelerated 1530 years ms patients compared unaffected peerspmid33860717 doi101177 13524585211007739,0.0
quot managing fatiguequot programme experiences shared ms participants scand j occup ther 2021 apr 16110 doi 101080 1103812820211905057 online ahead printabstractbackground managing fatigue mf programme can help people living multiple sclerosis ms manage fatigue everyday lives programme proven feasible swedish occupational therapists lack knowledge ms participants experience programme learned participating programmeaim describe swedish ms participants experience content structure swedish mf programme well learned participating programmematerial methods qualitative interviews performed nine ms participants data analysed according direct content analysisresults participants experienced programme material relevant valued structured sessions utilised different teaching forms participants described group format experienced course leader nurtured learning process learned occupational skills save energy revalue daily occupations initiated process change individual support needed programme completionconclusion significance findings support programme feasibility among ms participants show importance able practice skills handle fatigue everyday life future studies consider adding outcome measures focussing engagement occupations evaluating programme effectivenesspmid33861175 doi101080 1103812820211905057,0.0
falsepositive case brain 18 fcholine pet mr due tumefactive multiple sclerosis case report rev esp med nucl imagen mol 2021 apr 12s2253654x 21 00055x doi 101016 jremn202102013 online ahead printno abstractpmid33858799 doi101016 jremn202102013,0.0
switch sequestering anticd20 depleting treatment disease activity outcomes washout first 6 months ocrelizumab therapy mult scler 2021 apr 1513524585211005657 doi 101177 13524585211005657 online ahead printabstractobjectives switching treatments opportunity patients multiple sclerosis ms ameliorate disease control safety aim study investigate impact switching fingolimod fty natalizumab ntz ocrelizumab ocr disease activitymethods retrospectively enrolled 165 patients treated ocr 11 ms centres assessed association demographic clinical characteristics relapse rate rr activity magnetic resonance imaging mri washout 6 months treatment ocr univariable multivariable negative binomial regression modelsresults registered total 35 relapses washout period previous treatment fty relapses previous year relapsingremitting course associated higher rr first 6 months ocr 12 patients clinical mri disease activity higher expanded disability status scale edss higher lymphocyte count ocr start associated reduced probability relapsediscussion conclusion study confirms withdrawal sequestering agents fty increases risk relapses washout period nevertheless starting ocr achieving complete immune reconstitution limit effectiveness first 6 months probably trapped lymphocytes escape cd20mediated depletionpmid33855897 doi101177 13524585211005657,0.0
different susceptibility t b cells cladribine depends levels deoxycytidine kinase activity linked activation status j neuroimmune pharmacol 2021 apr 14 doi 101007 s11481021099943 online ahead printabstractdeoxycytidine kinase dck 5 deoxynucleotidase nt5c2 involved metabolism cladribine 2cda immunomodulatory drug multiple sclerosis mediating phosphorylation activation phosphorolysis deactivation 2cda respectively enzymes promote prevent accumulation cell leads cell death particular lymphocytes present high intracellular dck nt5c2 ratio sensitive 2cda immune cells aim determining expression enzymes activity differ specific progenitor mature immune cells influenced cellular activation exposure 2cda flow cytometry analysis showed difference dck nt5c2 ratio progenitor mature immune cells 2cda induced apoptosis stimulated t b cells unstimulated b cells dck expression enhanced 2cda mrna protein levels activated t cells mrna level activated b cells dck activity measured inhouse luminescence release enzyme assay higher activated t b cells increase abrogated activated b cells t cells upon exposure 2cda results reveal important relationship dck activity effect 2cda b t cells according activation status study warranted evaluate whether dck activity future suitable predictive biomarker lymphocyte response 2cdapmid33851318 doi101007 s11481021099943,0.0
overview neuroprotective effects maoinhibiting antidepressant phenelzine cell mol neurobiol 2021 apr 10 doi 101007 s10571021010783 online ahead printabstractphenelzine plz monoamine oxidase mao inhibiting antidepressant anxiolytic properties multifaceted drug number pharmacological neurochemical effects addition inhibition mao findings effects contributed body evidence indicating plz also neuroprotective neurorescue properties attributes reviewed paper include catabolism active metabolite phenylethylidenehydrazine peh effects plz peh gabaglutamate balance brain sequestration reactive aldehydes inhibition primary amine oxidase also discussed encouraging findings effects plz animal models stroke spinal cord injury traumatic brain injury multiple sclerosis well actions reduction nitrative stress reduction effects toxin dopaminergic neurons potential anticonvulsant actions effects brainderived neurotrophic factor neural cell adhesion molecules antiapoptotic factor brain levels ornithine nacetylamino acidspmid33839994 doi101007 s10571021010783,1.0
clinical features visual outcome poor prognostic factors occlusive retinal vasculitis can j ophthalmol 2021 apr 7s00084182 21 000910 doi 101016 jjcjo202103001 online ahead printabstractobjective investigate clinical features treatment visual outcome occlusive retinal vasculitis orv focal analysis prognostic factors associated poor visual outcomemethods conducted retrospective cohort study patients diagnosed orv least 6 months followup demographic data ocular features best corrected visual acuity bcva fluorescein angiography therapy regimens outcomes collected massachusetts eye research surgery institution database 2006 2017 multivariate logistic regression performed analyze factors independently predicting poor visual outcomeresults fifthtwo patients 69 eyes enrolled 42 noninfectious cause 9 infectious cause 1 masquerade uveitis systemic inflammatory diseases including necrotizing vasculitis sarcoidosis multiple sclerosis systemic lupus erythematosus behets disease comprised causes orv forty 42 patients noninfectious orv received immunomodulatory therapy imt 35 patients 875 able achieve steroidfree remission compared bcva initial visit 066 011 logmar significant improvement recent visit 037 007 logmar p 0001 multivariate analysis demonstrated optic nerve atrophy macular ischemia poor bcva initial presentation independently correlated poor visual outcomeconclusions orv caused wide spectrum systemic inflammatory diseases aggressive imt preferred achieve steroidfree durable remission noninfectious orv optic nerve atrophy macular ischemia poor bcva initial visit predict poor visual outcomepmid33838140 doi101016 jjcjo202103001,0.0
longitudinal imaging tcells inflammatory demyelination preclinical model multiple sclerosis using 18 ffarag pet mri j nucl med 2021 apr 9jnumed120259325 doi 102967 jnumed120259325 online ahead printabstractlymphocytes innate immune cells key drivers multiple sclerosis ms main target ms disease modifying therapies dmt ex vivo analyses ms lesions revealed cellular heterogeneity variable tcell levels may important implication patient stratification choice dmt although magnetic resonance imaging mri proven valuable monitor dmt efficacy lack specificity cellular subtypes highlights need complementary methods improve lesion characterization evaluated potential 2deoxy2 18f fluoro9darabinofuranosylguanine 18ffarag pet imaging noninvasively assess infiltrating tcells provide combination mri novel tool determine lesion types methods used novel ms mouse model combines cuprizone experimental autoimmune encephalomyelitis eae reproducibly induce two brain inflammatory lesion types differentiated tcell content 18ffarag pet imaging t2weighted mri t1weighted contrastenhanced mri performed prior disease induction demyelination high levels innate immune cells following tcell infiltration fingolimod immunotherapy used evaluate ability pet mri detect therapy response ex vivo immunofluorescence analyses tcells microglia macrophages myelin blood brain barrier bbb integrity performed validate vivo findings results 18ffarag signal significantly increased brain spinal cord time point tcell infiltration 18ffarag signal white matter corpus callosum grey matter cortex hippocampus correlated tcell density t2weighted mri detected white matter lesions independently tcells t1weighted contrastenhanced mri indicated bbb disruption time point tcell infiltration fingolimod treatment prevented motor deficits decreased tcell microglia macrophage levels agreement 18ffarag signal decreased brain spinal cord fingolimodtreated mice t1weighted contrastenhanced mri revealed intact bbb t2weighted mri remained unchanged conclusion combination mri 18ffarag pet enables detection inflammatory demyelination tcell infiltration ms mouse model providing new way evaluate lesion heterogeneity disease progression following dmt upon clinical translation methods hold great potential patient stratification monitoring ms progression therapy responsespmid33837066 doi102967 jnumed120259325,1.0
serum inflammatory markers patients multiple sclerosis association clinical manifestations mri findings acta neurol belg 2021 apr 9 doi 101007 s13760021016479 online ahead printabstractinflammation myelinated portion nervous system mainstay multiple sclerosis ms elevation inflammatory markers procalcitonin esr hscrp suspected occur ms patients however prognostic role relationship severity clinical symptoms ms mri evidences remained unnoticed literature hence aim evaluate serum level inflammatory markers acute attack ms patients demonstrate potential prognostic role inflammatory markers study carried case control groups definite ms patients cases patients active ms allocated four subgroups control group included patients nonactive ms furthermore participants underwent brain cervical magnetic resonance imaging mri using contrast agent significant difference detected hscrp level p 0009 across subgroups cases highest level hscrp reported patients cerebellar brain stem symptoms mean 699813 350116 lowest patients pyramidal urinary incontinence symptoms mean 195891 266216 moreover correlation coefficient values mri contrastenhanced lesions esr level statistically significant rs 0503 p 0001 elevation esr serum level positively correlates disease activity evidenced values contrastenhanced plaques mri relapsingremitting ms patients may predict disease activity addition ms relapse cerebellar brain stem symptoms associated high concentration hscrp plasma levelpmid33837496 doi101007 s13760021016479,1.0
impact adherence diseasemodifying therapies employment among veterans multiple sclerosis disabil rehabil 2021 apr 716 doi 101080 0963828820211907621 online ahead printabstractpurpose patients adhere diseasemodifying therapies dmts lower rate msrelated relapses disability sought determine adherence rate dmts association adherence dmts employment patients multiple sclerosis ms method one hundred fortytwo patients ms periodically followed clinic january 2000 january 2020 compared three groups patients defined according adherence dmts nonadherent poorly adherent adherent obtaining paid employmentresults fortyseven ms patients 331 nonadherent dmt medication 88 ms patients 620 demonstrated good 7 49 poor adherences patients goodadherence group paid employment 420 compared 234 nonadherent group p 0587 controlling potential cofoundersconclusion study veterans adhered dmts 24 times likely paidemployment compared non poorlyadherent patients clinical significance study encourage ms patients adhere dmts motivating factor paidemploymentimplications rehabilitationwhat known subject setting randomized controlled trial adherence rates reported different injectable dmts vary 7985 week interferon beta1a im ifnb1a 4978 injectable dmtswhat new findings impact clinical practicepaid employment common among veterans whose adherence dmts good 420 employed poor 429 among nonadherent 234 veterans adhered dmts also younger less severe ms displayed less cognitive physically impairment adherebeing employed can act motivating factor encourage adherence treatment aimed preventing accumulation mental physical disabilitiespmid33826431 doi101080 0963828820211907621,0.0
relevance brain mri patients uveitis retrospective cohort 402 patients ocul immunol inflamm 2021 apr 717 doi 101080 0927394820201870145 online ahead printabstractaim assess diagnostic value brain magnetic resonance imaging bmri etiological diagnosis uveitis establish predictive factors associated advantageous usemethods retrospective study patients de novo uveitis referred tertiary hospital underwent bmri 2003 2018results bmri contributive 19 402 cases 5 among patients contributive bmri 68 neurological signs univariate analysis established neurological signs p 001 granulomatous uveitis p 003 retinal vasculitis p 002 intermediate uveitis p 001 significantly associated contributive bmri multivariate analysis confirms significant association neurological signs p 001 intermediate uveitis p 01 conclusion bmri appears relevant exam specific cases intermediate posterior uveitis panuveitis accompanied neurological signs retinal vasculitis patients older 40 rule oculocerebral lymphomaabbreviations ace angiotensinconverting enzyme bmri magnetic resonance imaging cbc complete blood cell count bmri brain magnetic resonance imaging ct computerized tomography ms multiple sclerosis ns neurological signs ocl oculocerebral lymphoma ris radiologically isolated syndromepmid33826481 doi101080 0927394820201870145,0.0
topical rapamycin treatment facial angiofibromas tuberous sclerosis systematic review based evidence j dermatolog treat 2021 apr 617 doi 101080 0954663420211905768 online ahead printabstractintroduction facial angiofibromas tuberous sclerosis prevalent cutaneous manifestation affecting 80 patients cause facial lesions negative psychosocial consequences newly topical rapamycin established effective safe therapy skin conditionpurpose analyze available scientific evidence effectiveness safety topical sirolimus treatment facial angiofibromas tuberous sclerosismethods literature search conducted pubmed cochrane effectiveness safety analyzed along main characteristics formulation included studiesresults thirty studies included involving total 508 patients developed last 20 years four randomized clinical trial 17 case series 9 single case reports founded multiple topical rapamycin concentrations 00031 formulations gel ointment solution found literature rapamycin demonstrated effectiveness studies included except 5 patients 1 b study rapamycin shown safe treatment faconclusions topical sirolimus can considered effective safety option treatment facial angiofibromas tuberous sclerosis however longterm studies need establish evidencebased therapeutic protocolkey messageupdated review date topical rapamycin facial angiofibromas allowing support therapeutic decisionspmid33821748 doi101080 0954663420211905768,0.0
nad+ metabolism immune response autoimmunity inflammageing br j pharmacol 2021 apr 5 doi 101111 bph15477 online ahead printabstractmetabolism dynamically regulated accompany immune cell function altered immunometabolism can result impaired immune responses concomitantly pharmacological manipulation metabolic processes offers opportunity therapeutic intervention inflammatory disorders nicotinamide adenine dinucleotide nad+ critical metabolic intermediate serve enzyme cofactor redox reactions also used cosubstrate multiple enzymes sirtuins adenosine diphosphate ribose transferases synthases activities nad+ metabolism regulates broad spectrum cellular functions energy metabolism dna repair regulation epigenetic landscape inflammation thus manipulation nad+ availability using pharmacological compounds nad+ precursors can immunemodulatory properties inflammation herein discuss nad+ metabolism contributes immune response inflammatory conditions special focus multiple sclerosis inflammatory bowel diseases inflammageingpmid33817782 doi101111 bph15477,0.0
sarscov2 infection seroprevalence patients multiple sclerosis neurologia 2021 mar 19s02134853 21 00058x doi 101016 jnrl202103005 online ahead printabstractintroduction effect sarscov2 infection patients multiple sclerosis ms influence diseasemodifying therapies dmt ms covid19 unknown date patients ms shown present greater risk covid19 severe progression diseasemethods performed descriptive study patients ms presenting sarscov2 infection diagnosed pcr analysed demographic clinical laboratory treatment variables sample presence antibodies virus also determinedresults relapsingremitting ms rrms frequent form ms sample prognosis unfavourable 102 patients associated older age higher scores expanded disability status scale edss seroprevalence antibodies sarscov2 833 sample development antibodies associated dmt lymphocytopaenia variables analysedconclusions incidence covid19 slightly lower sample general population province unfavourable prognosis associated older age higher edss scores dmt lymphocytopaenia influence clinical course covid19 seroprevalence antibodies virus sample similar reported general population positive pcr results virus influence specific dmts determinedpmid33812762 doi101016 jnrl202103005,0.0
hemicraniectomy externalized ventricular drain placement pediatric patient myelin oligodendrocyte glycoproteinassociated tumefactive demyelinating disease childs nerv syst 2021 apr 2 doi 101007 s00381021051392 online ahead printabstractbackground acquired demyelination central nervous system children can manifest multiple sclerosis neuromyelitis optica myelin oligodendrocyte glycoprotein mog associated demyelination acute monophasic illness without serum antibodies rarely patients demyelinating disease need surgical intervention fulminant crisescase report case antimog antibodyrelated tumefactive demyelination 10yearold female required urgent hemicraniectomy external ventricular drain placement progressive white matter edema obstructive hydrocephalus subfalcine transtentorial herniationpmid33796928 doi101007 s00381021051392,1.0
bilateral acute retinal necrosis treatment alemtuzumab multiple sclerosis eur j ophthalmol 2021 mar 3111206721211006576 doi 101177 11206721211006576 online ahead printabstractintroduction alemtuzumab humanized monoclonal antibody used treatment multiple sclerosis ms chronic lymphocytic leukemia decreases t cell count leading significant immunosuppression increased risk systemic ocular infections herein report unique case bilateral acute retinal necrosis arn caused varicellazoster virus vzv patient affected ms treatment alemtuzumabcase description 36yearold man relapsingremitting ms treatment alemtuzumab developed bilateral visual loss anterior segment examination displayed granulomatous keratic precipitates 3+ cells anterior chamber fundoscopy showed bilateral 1+ vitritis peripheral retinal necrosis complicated retinal detachment left eye high viral load vzv aqueous humor samples univocal interpretation viral reactivation addition systemic therapy acyclovir patient treated bilateral intravitreal injections foscarnet underwent parsplana vitrectomy silicone oil tamponade retinal detachment left eyeconclusion report shows unique case bilateral arn caused vzv associated alemtuzumab visual loss ms patients biologic therapy underestimated performing accurate differential diagnosis optic neuritispmid33789493 doi101177 11206721211006576,0.0
drugs used treatment multiple sclerosis covid19 pandemic critical viewpoint curr neuropharmacol 2021 mar 29 doi 102174 1570159x19666210330094017 online ahead printabstractsince covid19 emerged word public health problem attention focused immune suppressive drugs used treatment autoimmune disorders influence risk sarscov2 infection development acute respiratory distress syndrome ards discuss diseasemodifying agents approved treatment multiple sclerosis ms within context interferon ifn 1a 1b display antiviral activity protective early stage covid19 infection although sarscov2 may developed resistance ifns however hyper inflammation stage ifns may become detrimental facilitating macrophage invasion lung organs glatiramer acetate analogues interfere development covid19 may considered safe teriflunomide firstline oral drug used treatment relapsingremitting ms rrms may display antiviral activity depleting cellular nucleotides necessary viral replication firstline drug dimethyl fumarate may afford protection sarscov2 activating nrf2 pathway reinforcing cellular defences oxidative stress concern raised use secondline treatments ms covid19 pandemic however concern always justified example fingolimod might highly beneficial hyperinflammatory stage covid19 number mechanisms including reinforcement endothelial barrier caution suggested use natalizumab cladribine alemtuzumab ocrelizumab although ms disease recurrence discontinuation drugs may overcome potential risk covid19 infectionpmid33784961 doi102174 1570159x19666210330094017,0.0
perceived fatigue impact cognitive variability multiple sclerosis j int neuropsychol soc 2021 mar 31111 doi 101017 s1355617721000230 online ahead printabstractobjective people multiple sclerosis pwms healthy controls hcs evaluated cognitive variability indices examined relationship fatigue cognitive variability groups intraindividual variability iiv neuropsychological test battery hypothesized mediate group differences expected fatiguemethod fiftynine pwms 51 hcs completed psychosocial interview battery neuropsychological tests questionnaires 1day visit fatigue study measured fatigue impact scale fis selfreport multidimensional measure fatigue iiv operationalized using two different measures maximum discrepancy score mds intraindividual standard deviation isd two cognitive domains memory attention processing speed two mediation analyses group pwms hcs independent variable variability composite memory attention processing speed measures mediators total residual fatigue accounting age outcome depression covariate conducted baron kenny approach testing mediation process macro testing strength indirect effect usedresults results mediation analysis using 5000 bootstrap samples indicated iiv domains attention processing speed memory significantly mediated effect patient status total residual fatigueconclusion iiv objective performance measure related differences fatigue impact pwms hcs pwms experience variability across tests attention processing speed memory experience variable performance may increase impact fatiguepmid33785084 doi101017 s1355617721000230,0.0
linear brain atrophy measures multiple sclerosis clinically isolated syndromes 30year followup j neurol neurosurg psychiatry 2021 mar 30jnnp2020325421 doi 101136 jnnp2020325421 online ahead printabstractobjective determine 30year brain atrophy rates following clinically isolated syndromes relationship atrophy first 5 years clinical outcomes 25 years latermethods cohort 132 people presented clinically isolated syndrome suggestive multiple sclerosis ms recruited 19841987 clinical mri data collected prospectively 30 years widths third ventricle medulla oblongata used linear atrophy measuresresults 30 years 27 participants remained classified clinically isolated syndrome 34 converted relapsing remitting ms 26 secondary progressive ms 16 died due ms mean age baseline 317 years sd 75 mean disease duration 308 years sd 09 change medullary third ventricular width within first 5 years allowing white matter lesion accrual expanded disability status scale increases period predicted clinical outcome measures 30 years 1 mm medullary atrophy within first 5 years increased risk secondary progressive ms ms related death 30 years 583 583 95 ci 174 1961 p0005 using logistic regressionconclusions findings show brain regional atrophy within 5 years clinically isolated syndrome predicts progressive ms related death disability 25 years laterpmid33785581 doi101136 jnnp2020325421,0.0
circulating plasma micrornas systemic sclerosisassociated pulmonary arterial hypertension rheumatology oxford 2021 mar 30keab300 doi 101093 rheumatology keab300 online ahead printabstractobjectives systemic sclerosisassociated pulmonary arterial hypertension sscapah late devastating complication systemic sclerosis ssc early identification sscapah may improve survival examined role circulating micrornas mirnas sscapahmethods using quantitative rtpcr abundance mature mirnas plasma determined 85 female patients anticentromere antibody positive limited cutaneous ssc twentytwo patients sscapah sixtythree ssc controls without pah matched disease duration fortysix selected mirna plasma levels correlated clinical data longitudinal samples analysed 14 sscapah 27 ssc patientsresults disease duration 12 years sscapah patients 127 years ssc controls plasma expression levels 11 mirnas lower patients sscapah four mirnas displayed higher plasma levels sscapah patients compared ssc controls significant difference groups mir20a5p mir203a3p correcting multiple comparisons p 0002 receiver operating characteristics curve showed auc 069083 mir215p mir20a5p combination mir20a5p mir203a3p correlated inversely ntprobnp levels r 042 047 mixed effect model analysis identify mirnas predictor pah development however mir20a5p plasma levels lower longitudinal samples sscapah patients ssc controlsconclusions study links expression levels circulating plasma mirnas especially mir20a5p mir203a3p occurrence sscapah female patients anticentromere antibody positive limited cutaneous sscpmid33784391 doi101093 rheumatology keab300,0.0
systematic review gender bias clinical trials monoclonal antibodies treatment multiple sclerosis neurologia 2021 mar 25s02134853 21 000086 doi 101016 jnrl202101003 online ahead printabstractintroduction article analyses presence gender bias clinical trials monoclonal antibodies used treat multiple sclerosismaterial methods performed systematic review controlled clinical trials 4 monoclonal antibodies used treat multiple sclerosis natalizumab rituximab alemtuzumab ocrelizumab searched pubmed medline database articles published english march 2020 study conducted accordance relevant international recommendationsresults search identified 89 articles 55 met inclusion criteria patients included trials 646 women lead authors 10 studies women fifteen 55 studies included sexbased analysis primary endpoint 8 articles discussed results separately men womenconclusions clinical trials 4 monoclonal antibodies present significant gender bias cases primary secondary endpoints analyzed according patient sex despite fact international recommendations include minimum requirement ensuring scientific validity obtaining appropriate results extrapolation wider populationpmid33775476 doi101016 jnrl202101003,0.0
cannabis medical purposes crosssectional analysis health care professionals#39 knowledge j assoc nurse pract 2021 mar 19 doi 101097 jxx0000000000000590 online ahead printabstractbackground legalization cannabis use evidence base supporting risks benefits cannabinoids expanding understanding health care professionals hcps knowledge cannabis medical purposes limited understanding knowledge base knowledge gaps medical cannabis use critical advanced practice registered nurses aprns increasingly called manage patients taking multiple drugs including prescribed unprescribed cannabis prescription cannabinoidspurpose purpose study examine hcps knowledge clinical cannabis including laws regulations risks harms pharmacology effects pain multiple sclerosis spasticity seizures assessed written tests inperson continuing medical education programmethods total scores differences among professions topics comparedresults total 178 226 program attendees completed test 79 107 47 physicians 30 13 aprns 18 8 registered nurses mean test score 632 sd 127 without significant differences among professions f 3 174 153 p 21 significant differences among topics 2 7 1068 20113 p 001 score lowest effects seizures 438 scores 70 areas except laws regulations 857 implications practice substantial gaps hcps knowledge clinical effects cannabis especially risks harms pharmacology effects pain multiple sclerosis spasticity seizures education may help hcps understand risks benefits cannabis cannabinoids across conditionspmid33767121 doi101097 jxx0000000000000590,0.0
incobotulinumtoxina versus onabotulinumtoxina intradetrusor injections patients neurogenic detrusor overactivity incontinence doubleblind randomized noninferiority trial minerva urol nephrol 2021 mar 26 doi 1023736 s2724605121042272 online ahead printabstractbackground randomized doubleblind noninferiority clinical study performed efficacy tolerability incobotulinumtoxina vs onabotulinumtoxina intradetrusor injections patients refractory neurogenic detrusor overactivity incontinence performing intermittent catheterizationmethods sixtyfour patients spinal cord injury multiple sclerosis randomized receive 30 intradetrusor injections incobotulinumtoxina onabotulinumtoxina 200 u 28 patients incobotulinumtoxina group 29 onabotulinumtoxina group completed study primary outcome measure noninferior variation baseline daily urinary incontinence episodes week 12 noninferiority margin one episode day secondary outcomes measures changes incontinence quality life questionnaire visual analog scale score bother symptoms quality life urodynamic parameters occurrence adverse effects related costs week 12 results week 12 mean value difference urinary incontinence episodes day two groups 02 95 twosided ci 1 07 difference incontinence episodes day two groups 04 higher limit onesided 95 ci 02 episodes day much lower noninferiority margin one episode day total score subscores incontinence quality life questionnaire visual analog scale scores urodynamics show differences two groups adverse effects similar treatments urinary tract infection frequent localised effect minor costs observed following incobotulinumtoxinaconclusions patients refractory neurogenic incontinence due spinal cord injury multiple sclerosis incobotulinumtoxina inferior onabotulinumtoxina improving clinical urodynamic findings shortterm followup comparable adverse effects minor costspmid33769020 doi1023736 s2724605121042272,0.0
impact covid19 multiple sclerosis care management results european committee treatment research multiple sclerosis survey mult scler 2021 mar 2513524585211005339 doi 101177 13524585211005339 online ahead printabstractbackground spread coronavirus disease19 covid19 poses unique challenges management people multiple sclerosis pwms objectives collect data impact covid19 emergency access care pwms ms treatment practicesmethods march july 2020 european committee treatment research multiple sclerosis ectrims promoted online survey covering patient access care management relapses visits diseasemodifying therapy dmt experience covid19results threehundred sixty neurologists 52 countries 68 europe completed survey 98 reported covid19related restrictions telemedicine adopted overcome limited access care newly activated 73 widely implemented 17 70 reported changes dmt management interferons glatiramer considered safe dimethyl fumarate teriflunomide fingolimod considered safe except patients developing lymphopenia modifications considered natalizumab 64 cladribine 24 anticd20 22 alemtuzumab 17 18 alemtuzumab cladribine 43 anticd20 considered postponing treatmentconclusion ectrims survey highlighted challenges keeping standards care clinical practice telemedicine clearly needs implemented gathering data dmt safety will remain crucial inform treatment decisionspmid33764197 doi101177 13524585211005339,0.0
acute psychotic episode primary clinical manifestation multiple sclerosisa case report nervenarzt 2021 mar 24 doi 101007 s0011502101107y online ahead printno abstractpmid33763707 doi101007 s0011502101107y,0.0
clinically isolated syndrome diagnosis risk developing clinically definite multiple sclerosis neurologia 2021 mar 20s02134853 21 000281 doi 101016 jnrl202101011 online ahead printabstractintroduction cases multiple sclerosis ms initially presents clinically isolated syndrome cis differentiating cis acute subacute neurological diseases estimating risk progression clinically definite ms essential since presenting second episode short time associated poorer longterm prognosisdevelopment conducted literature review evaluate usefulness different variables improving diagnostic accuracy predicting progression cis ms including magnetic resonance imaging mri biofluid markers oligoclonal igg igm bands lipidspecific oligoclonal igm bands csf csf kappa free lightchain kflc index neurofilament light chain nfl csf serum chitinase 3like protein 1 chi3l1 csf serumconclusions codetection oligoclonal igg bands mri lesions reduces diagnostic delays suggests high risk cis progression ms kflc index 106 csf nfl concentrations 1150 ng l indicate cis likely progress ms within one year 4050 90 patients cis serum chi3l1 levels 33 ng ml 100 lipidspecific oligoclonal igm bands present ms within one year cis onsetpmid33757657 doi101016 jnrl202101011,0.0
behcet#39 s disease associated multiple sclerosis rheumatoid arthritis korean populationbased study dermatology 2021 mar 2316 doi 101159 000514634 online ahead printabstractbackground epidemiologic study previously reported associations among behets disease bd autoimmune disordersobjectives investigate association bd autoimmune disorders multiple sclerosis rheumatoid arthritismethods medical records patients newly diagnosed bd n 6 214 20122017 analyzed using data entered large nationwide database 2007 2017 age sexmatched control population individuals without bd sampled ratio controlsbd cases 31 n 18 642 cohorts analyzed presence multiple sclerosis rheumatoid arthritis within minimum 5 years prior bd diagnosisresults patients bd significantly higher odds ratios ors multiple sclerosis 885 95 ci 2363317 rheumatoid arthritis 462 95 ci 335635 control group adjustment diabetes mellitus hypertension dyslipidemia bd patients aged 40 years higher proportion rheumatoid arthritis 2391 95 ci 5501039 older patients 396 95 ci 283554 conclusion results suggest bd associated multiple sclerosis rheumatoid arthritispmid33756455 doi101159 000514634,0.0
investigation less known effects manual lymphatic drainage narrative review lymphat res biol 2021 mar 22 doi 101089 lrb20190091 online ahead printabstractintroduction manual lymphatic drainage mld one components complex decongestive physiotherapy accepted gold standard treatment lymphedema used therapeutic purposes many diseases wellknown feature mld helps reduce edema addition reducing edema mld many effects increasing venous flow reducing fatigue raising pain threshold best knowledge study examining effects mld effects edema detail aim study compile effects mld provide better understanding effects mld methods literature search conducted medline embase cochrane library july 2019 identify different effects mld articles chosen first reading abstract subsequently data analyzed reading entire text fulltext resources undertake study collected information published different effects mld last 30 years 19892019 according results 20 studies met inclusion criteria conclusions study suggests mld can used symptomatic treatment various diseases multiple sclerosis parkinsons disease considering effects mld systemspmid33751912 doi101089 lrb20190091,0.0
cognition acute relapses psychometric evaluation correlation eventrelated potential p300 multiple sclerosis appl neuropsychol adult 2021 mar 21110 doi 101080 2327909520211897815 online ahead printabstractobjective acute relapses multiple sclerosis ms physical symptoms attract utmost care however cognitive impairment may constitute substantial part new relapse study evaluated cognitive status ms patients acute relapsesmaterials methods enrolled 35 definite ms patients 21 healthy subjects neuropsychometric tests eventrelated potential p300 administered ms patients corticosteroid treatment 3 months later control subjects tested onceresults differences scores timed 25foot walk test brief repeatable battery subtests 10 36 spart sdmt srt srtltm relapse remission phases statistically significant p 005 p 007 p 05 p 029 p 001 respectively latencies p300 waves relapses significantly prolonged ones remission controls p 004 p 001 respectively conclusions study observed significant involvement visualspatial perception remote memory recall well p300 latencies acute relapses inclusion cognitive assessment relapse can provide accurate information cognitive status future treatment modalitiespmid33749422 doi101080 2327909520211897815,0.0
recommendations coordination neurology neuroradiology departments management patients multiple sclerosis neurologia 2021 mar 17s02134853 21 000293 doi 101016 jnrl202101012 online ahead printabstractintroduction magnetic resonance imaging mri widely used diagnosis followup patients multiple sclerosis ms coordination neurology neuroradiology departments crucial performing interpreting radiological studies efficiently accurately possible however improvements can made communication departments many spanish hospitalsmethods panel 17 neurologists neuroradiologists 8 spanish hospitals held inperson online meetings draft series good practice guidelines coordinated management ms drafting process included 4 phases 1 establishing scope guidelines methodology study 2 literature review good practices recommendations use mri ms 3 discussion consensus experts 4 validation contentsresults expert panel agreed total 9 recommendations improving coordination neurology neuroradiology departments recommendations revolve around 4 main pillars 1 standardising process requesting scheduling mri studies reports 2 designing common protocols mri studies 3 establishing multidisciplinary committees coordination meetings 4 creating formal communication channels departmentsconclusions consensus recommendations intended optimise coordination neurologists neuroradiologists ultimate goal improving diagnosis followup patients mspmid33744061 doi101016 jnrl202101012,0.0
bmp tgf signaling modulator neurodegeneration als dev dyn 2021 mar 21 doi 101002 dvdy333 online ahead printabstractthis commentary focuses emerging intersection bmp tgf signaling roles nervous system function amyotrophic lateral sclerosis als disease state future research critical elucidate molecular underpinnings intersection cellular processes disrupted als influenced bmp tgf signaling including synapse structure neurotransmission plasticity neuroinflammation knowledge promises inform us ideal entry points targeted modulation dysfunctional cellular processes effort abrogate als pathologies likely different interventions required either discrete points disease progression across multiple dysfunctional processes together lead motor neuron degeneration death discuss challenging intriguing idea modulation pleiotropic nature bmp tgf signaling advantageous way simultaneously treat defects one cell process across different forms als article protected copyright rights reservedpmid33745185 doi101002 dvdy333,0.0
clinical paraclinical manifestations tuberous sclerosis complex children acta neurol belg 2021 mar 18 doi 101007 s1376002101635z online ahead printabstracttuberous sclerosis complex tsc autosomaldominant multisystem neurocutaneous disorder characterized hamartomas multiple organs study aimed evaluate clinical paraclinical manifestations children tsc clinical paraclinical characteristics 79 children tsc evaluated possible correlations factors calculated among studied children composed 41 females 519 38 males 481 skin manifestations hypopigmented macules well brain involvement cortical tubers 100 cases seizure 74 937 subependymal nodules 73 924 patients common findings renal angiomyolipoma diagnosed 36 706 51 patients subependymal giant cell astrocytoma 25 3 54 46 patients retinal hamartoma 15 429 35 patients cardiac rhabdomyoma 17 413 46 patients diagnosed furthermore 50 633 79 patients psychological disorders significant correlation prevalence seizures p 0002 given multisystemic involvement tsc necessary organs patients even without related clinical symptom sign examined regularly proper therapeutic intervention prevent disease progression growth hamartomas brain kidneys can lifethreatening therefore organs importance regularly followed examinedpmid33738777 doi101007 s1376002101635z,0.0
shear wave elastography evaluation brachial plexus multiple sclerosis acta radiol 2021 mar 172841851211002828 doi 101177 02841851211002828 online ahead printabstractbackground multiple sclerosis ms chronic neuroinflammatory disease characterized inflammation involving peripheral nerves shear wave elastography swe potentially method choice detecting peripheral nerve involvementpurpose compare degree thickening nerve elasticity brachial plexus bp nerve roots evaluate usefulness sonoelastography patients clinically diagnosed ms without brachial plexopathymaterial methods thirtytwo patients ms 32 controls included study bilateral c5 c6 c7 mean nerve root diameters mean elasticity values kilopascal kpa measured patient control groups relationship age height weight values nerve diameterelasticity values patient control groups comparedresults elasticity values c5 c6 nerve roots increased nerve root thickness decreased ms group compared control p 005 difference c7 mean nerve root elasticity kpa diameter measurements patient control groups p 005 conclusion study showed increase bp nerve root elasticity values kpa patients ms compared control group decrease diameter values thought related possible chronic atrophic process results consistent demyelinating process peripheral nervous system pns due mspmid33730859 doi101177 02841851211002828,1.0
nonlateonset neutropaenia following treatment multiple sclerosis ocrelizumab neurologia 2021 mar 13s02134853 21 000268 doi 101016 jnrl202101010 online ahead printabstractlateonset neutropaenia defined absolute neutrophil count 15103cells l starting4 weeks last dose rituximab absence identifiable causes lateonset neutropaenia rare adverse reaction rituximab observed approximately 5 patients rheumatic diseases constitute main indication rituximab patients neutropaenia appears mean of28 days ocrelizumab another monoclonal antibody binds cd20 glycosylated phosphoprotein mainly expressed membranes blymphocytes january 2018 approved treatment relapsingremitting primary progressive multiple sclerosis present case neutropaenia following intravenous infusion ocrelizumab patient primary progressive multiple sclerosis presented neutropaenic fever herpetic stomatitis ecthyma gangrenosum 20 days infusionpmid33726971 doi101016 jnrl202101010,0.0
significant higherlevel cc motif chemokine ligand 2 3 chemotactic power cerebral white matter grey matter rat human eur j neurosci 2021 mar 16 doi 101111 ejn15187 online ahead printabstractrecent observations indicate cerebral white matter wm exhibits higher chemoattractant capability immune cells cc motif chemokine ligand 2 3 ccl2 ccl3 key chemokines monocytes tcells however tissue differential chemokines unclear though higher ccl2 3 mrna levels found rodent wm shown immune cells infiltrated wm grey matter gm multiple sclerosis ms human simian immunodeficiency virus hiv siv infected brains nodular lesions also identified wm patients ms hiv siv encephalitis hypothesize higher levels ccl2 3 wm may associate neuropathogenesis test hypothesis compared ccl2 ccl3 peptide levels wm gm rat human found significantly higher wm next tested effect ccl2 primary rat microglia migration observed dosedependent migratory pattern assessed effects wm gm homogenates microglia chemotaxis observed significant stronger effects wm gm concentrationdependent manner concentrationdependent pattern tissue homogenates chemotaxis similar effect ccl2 finally found chemoattractant effects wm microglia significantly attenuated addition ccl2 receptor blocker culture medium neutralizing antibody ccl3 functional motif wm homogenate taking together results suggest ccl2 3 played significant roles microglia chemotaxis towards wm homogenatepmid33725384 doi101111 ejn15187,0.0
time walking aid 65 years ocrelizumab treatment patients relapsing multiple sclerosis data opera opera ii trials eur j neurol 2021 mar 16 doi 101111 ene14823 online ahead printabstractbackground requiring walking aid fundamental milestone ms represented expanded disability status scale edss score 60 assess effect ocrelizumab time edss60 relapsing msmethods time edss60 confirmed 24 48 weeks assessed 65 years 336 weeks doubleblind openlabel extension periods opera nct01247324 opera ii nct01412333 results time reach edss60 significantly delayed initially randomized ocrelizumab versus interferon 65 years risk requiring walking aid confirmed 24 weeks 34 lower among initiated ocrelizumab earlier vs delayed treatment average hr dbp+ole 95ci 066 045095 p 0024 risk requiring walking aid confirmed 48 weeks 46 lower average hr dbp+ole 95ci 054 035083 p 0004 conclusion reduced risk requiring walking aid earlier initiators ocrelizumab demonstrates longterm implications earlier highly effective treatmentpmid33724637 doi101111 ene14823,0.0
risk requiring wheelchair primary progressive multiple sclerosis data oratorio trial msbase registry eur j neurol 2021 mar 16 doi 101111 ene14824 online ahead printabstractbackground reaching expanded disability status scale edss 70 represents requirement wheelchair 1 assess effect ocrelizumab time edss 70 oratorio nct01194570 doubleblind extended controlled periods dbp+ecp 2 quantify likely longterm benefits extrapolating results 3 assess plausibility extrapolations using independent realworld cohort msbase registry actrn12605000455662 methods posthoc analyses assessing time 24week confirmed edss 70 two cohorts patients ppms baseline edss 3065 investigated oratorio msbaseresults oratorio dbp+ecp ocrelizumab reduced risk 24week confirmed edss 70 hazard ratio054 95ci 031092 p 0022 extrapolated median time 24week confirmed edss 70 121 192 years placebo ocrelizumab respectively 71year delay 95ci 43184 msbase median time 24week confirmed edss 70 124 yearsconclusion compared placebo ocrelizumab significantly delayed time 24week confirmed wheelchair requirement oratorio plausibility extrapolated median time reach milestone placebo group supported observed realworld data msbase extrapolated benefits ocrelizumab placebo represent truly meaningful delay loss ambulation independencepmid33724638 doi101111 ene14824,0.0
recurrent intracranial hemorrhage patient relapsing multiple sclerosis interferonbeta therapy neurologia 2021 mar 12s02134853 21 000116 doi 101016 jnrl202102002 online ahead printno abstractpmid33722454 doi101016 jnrl202102002,0.0
familial coexistence demyelinating diseases familial mediterranean fever rheumatol int 2021 mar 13 doi 101007 s00296021048217 online ahead printabstractfamilial mediterranean fever fmf monogenic autoinflammatory disease characterized fever serositis attacks caused mutations mediterranean fever mefv gene encoding pyrin gene gain function mutations pyrin gene lead stimulation proinflammatory cytokines persistent proinflammatory situation course fmf may play role development inflammatory diseases behcets disease psoriasis vasculitis multiple sclerosis ms demyelinating disorder also commonly seen fmf patients compared general population scarcely research reporting two diseases coexist one person family discovered cases fmf demyelinating disorders five members two different families besides two families reporting four families reported far combined data six families present casebased review study aimed draw attention physicians familial cooccurence fmf demyelinating disorders also discuss possible mechanisms coexistence two diseases light literaturepmid33715072 doi101007 s00296021048217,1.0
vagus nerve somatosensoryevoked potential neural disorders systematic review illustrative vignettes clin eeg neurosci 2021 mar 1215500594211001221 doi 101177 15500594211001221 online ahead printabstractobjective review scientific publications reporting vagal nerve somatosensoryevoked potential vsep findings individuals brain disorders present novel physiological explanations vsep origin methods systematic review papers reporting vsep findings individuals brain disorders controls evaluated papers published 2003 date indexed pubmed web science scielo databases extracted following information number patients controls type neural disorder age gender stimulating recording grounding electrodes well stimulus side intensity duration frequency polarity information physiological parameters neurobiological variables correlation studies also reviewed representative vignettes included add support conclusions results vsep studied 297 patients neural disorders parkinsons disease pd alzheimers disease vascular dementia mild cognitive impairment subjective memory impairment major depression multiple sclerosis scalp responses marked vsep showed high variability low validity poor reproducibility vsep latencies amplitudes correlate disease duration unified pd rating scale score heart function pd patients cerebrospinal fluid amyloid phosphor cognitive tests patients mental disorders vignettes demonstrated vsep volume conduction propagating muscles surrounding scalp recording electrodes conclusion vsep brainevoked potential neural origin muscle activity induced electrical stimulation tragus region ear review illustrative vignettes argue assessing parasympathetic system using socalled vseppmid33709798 doi101177 15500594211001221,0.0
early factors associated later conversion multiple sclerosis patients presenting isolated myelitis j neurol neurosurg psychiatry 2021 mar 9jnnp2020325274 doi 101136 jnnp2020325274 online ahead printabstractobjective identify early clinical paraclinical factors may help predict later conversion multiple sclerosis ms patients presenting isolated myelitis ie transverse myelitis without clinical radiological evidence inflammation demyelination elsewhere central nervous system methods retrospective cohort study included patients isolated myelitis followed clinically radiologically specialised myelopathy clinic excluded patients ms onset aquaporin4igg seropositivity myelin oligodendrocyte glycoproteinigg seropositivity identified aetiology logistic regression used identify factors predictive conversion ms defined 2017 mcdonald criteria results included 100 patients followed median 43 years conversion ms occurred 25 77 patients 32 shortsegment myelitis longest lesion spanning 3 vertebral segments mri compared 0 23 patients 0 longitudinally extensive myelitis p0002 among patients shortsegment myelitis factors identified highly predictive conversion ms using multivariate logistic regression included cerebrospinal fluid csf restricted oligoclonal bands ocb 92 95 ci 21 410 p0004 younger age 11 year younger 95 ci 10 11 p004 longer followup 13 year longer 95 ci 10 16 p004 conversion ms occurred median 28 years myelitis onsetconclusions shortsegment mri cord lesion s csfrestricted ocb younger age longer followup factors predictive conversion ms patients presenting isolated myelitispmid33687973 doi101136 jnnp2020325274,1.0
dysregulation sirt1 signaling multiple sclerosis neuroimmune disorders systematic review sirtuin activators potential immunomodulators influences dysfunctions endocr metab immune disord drug targets 2021 mar 8 doi 102174 1871530321666210309112234 online ahead printabstractimmune dysregulation neuronal inflammation oligodendrocyte degradation key causes autoimmune disorders like multiple sclerosis ms various otherimmune dysregulated neurodegenerative complications responsible cnsmediated immune responsessirtuins sirt1 nicotinamide adenosine dinucleotide nad dependent transcriptional protein thatdeacetylases removes acetyl groups transcription factors like p53 foxo nfb pgc1 sirt1 mediates wide range physiological functions including gene transcription metabolism neuronal apoptosis glucose productionsirt1 dysregulation targets transcription factors molecular alterations gene expression modification influence neuronal plasticity inhibits th17 cells interleukin1 can aggravate brain diseasespreclinical clinical findings show upregulation sirt1 reduces autoimmunity neurodegeneration neuroexcitation even though drugs developed symptomatic therapies clinical trials particular pharmacological implications improving postoperative conditions neurodegenerativepatients intensive care requiredunderstanding sirt1 signaling identifying immunemediated neuron deterioration can detect major therapeutic interventions prevent neurocomplicationsthus current review addressed manifestations disease downregulation sirt1 potentially cause ms neurodegenerative disorders provided data existing available effective drug therapies disease management strategiespmid33687904 doi102174 1871530321666210309112234,0.0
imperative role glycosylation human moghla interaction molecular insights mogab associated demyelination j biomol struct dyn 2021 mar 4111 doi 101080 0739110220211893816 online ahead printabstractmyelin oligodendrocyte glycoprotein transmembrane protein found outer lamella myelin sheath autoimmune attack mog leads demyelination differs normal multiple sclerosis mog three epitope regions mog122 mog3555 mog92106 extracellular region crucial mog3555 epitope human leukocyte antigen hla interaction initial step autoantibody generation study effective role glycosylation moghla interaction performed molecular dynamics simulations complex hla interacts three mog epitopes absence presence glycan results projected epitope mog122 decisive hla interaction absence glycan hla interacts epitope mog3555 irrespective glycan existence residues arg9 arg46 arg66 found interact strongly hla even presence glycan glycan increased flexibility hmog enhanced interaction mog water moleculespmid33663341 doi101080 0739110220211893816,1.0
serum based mirna diagnostic biomarker multiple sclerosis systematic review metaanalysis immunol invest 2021 mar 4116 doi 101080 0882013920211887888 online ahead printabstractthis systematic review metaanalysis aimed identify deferentially expressed serum mirnas multiple sclerosis patients evaluate diagnostic value multiple sclerosis diagnosis studies identified pubmed google scholar saudi digital library 30 september 2019 articles examined mirna expression level ms patients compared healthy control group included review data extracted three independent author comprehensive metaanalysis version 3 software used metaanalysis heterogeneity studies identified according i2 value literatures search identified 9 eligible articles concerning serum mirna diagnostic biomarker multiple sclerosis comparison healthy control group 19 serum mirnas differentially expressed ms patients identified 8 downregulated 11 upregulated 1 discordant result publications provided information specific mirna diagnostic value pooled auc 72 95 ci 065078 pvalue 000 overall multiple sclerosis patients primary progressive ms ppms 95 ci 066078 pvalue 000 mirna panel four mirnas showed high sensitivity 73 specificity 68 distinguishing multiple sclerosis control groups using single mirna mir145 sensitivity increased 79 specificity 87 available data literature metaanalysis suggests potential use serum mirna biomarkers early diagnosis ms high sensitivity specificity distinguishing multiple sclerosis subtypes healthy controlsabbreviation ms multiple sclerosis idd inflammatory demyelinating diseases rrms relapsingremitting multiple sclerosis ppms primary progressive multiple sclerosis spms secondary progressive multiple sclerosis nmo neuromyelitis optica mirna microrna ecmirna extracellular microrna auc area curve roc receiver operator characteristicpmid33660581 doi101080 0882013920211887888,1.0
autoimmune encephalitis proposed recommendations symptomatic longterm management j neurol neurosurg psychiatry 2021 mar 1jnnp2020325302 doi 101136 jnnp2020325302 online ahead printabstractthe objective paper evaluate available evidence step autoimmune encephalitis management provide expert opinion evidence lacking paper approaches autoimmune encephalitis broad category rather focusing individual antibody syndromes core authors autoimmune encephalitis alliance clinicians network reviewed literature developed first draft evidence lacking controversial electronic survey distributed members solicit individual responses sixtyeight members 17 countries answered survey popular bridging therapy oral prednisone taper chosen 38 responders rituximab popular maintenance therapy chosen 46 responders considered maintenance immunosuppression second relapse patients neuronal surface antibodies 70 seronegative autoimmune encephalitis 61 opposed onconeuronal antibodies 29 responders opted cancer screening 4 years patients neuronal surface antibodies 49 limbic encephalitis 46 opposed nonlimbic seronegative autoimmune encephalitis 36 detailed survey results presented manuscript summary diagnostic therapeutic recommendations presented conclusionpmid33649021 doi101136 jnnp2020325302,0.0
fingolimodassociated macular edema case report late onset eur j ophthalmol 2021 mar 11120672121999632 doi 101177 1120672121999632 online ahead printabstractintroduction authors present case male multiple sclerosis ms developed unilateral fingolimodassociated macular edema fame 10 years initiating fingolimod therapy reporting case study authors present comprehensive review fame current incidence therapy options ms patientscase description 58yearold caucasian male patient referred hospital history ms fingolimod treatment 10 years patient presented referring second episode blurred vision left eye os best corrected visual acuity bcva 20 20 right eye od 20 30 os dilated fundus examination os revealed dull foveal reflex retinal thickening spectral domain optical coherence tomography sdoct scan demonstrated increased central macular thickness 459 m foveal cysts subretinal fluid neurologists decided discontinue fingolimod treatment based ophthalmological findings three months post fingolimod discontinuation macular edema resolved bcva 20 20 od 20 25 os conclusions authors report case late onset fame fame may occur several years starting fingolimod treatment part differential diagnosis blurred vision patients receiving fingolimod microcystic macular edema secondary ms macular edema associated msinduced uveitis always excluded two conditions secondary ms might show lack drug effectiveness possible need changing existing therapy order prevent disease progresspmid33645300 doi101177 1120672121999632,0.0
connection jak stat ppargamma signaling progression multiple sclerosis insights modulation tcells immune responses brain curr mol pharmacol 2021 mar 1 doi 102174 1874467214666210301121432 online ahead printabstractmultiple sclerosis ms severe brain spinal cord condition diverse autoimmune response wide variety demyelination symptoms primarily affect young adults primary reason disease inflammation white grey matter caused increased production proinflammatory cytokines damages progenitor oligodendrocytes appears induce hypertrophy astrocytes gliosis overexpression jak stat signaling pathway contributes directly physiological pathological results motor neuron diseases cytokines il17 il6 il12 tnf inf use jak stat signaling trigger selfreactive cd4+ tcells differentiate th1 phenotypes overactivate immune reactions brain similarly ppar plays critical role regulating immune response providing antiinflammatory effect inhibiting macrophage cytokine production activation ppar also mediates intrinsic molecular process tcell selectively regulates differentiation th17 various studies indicate neuroprotective function ppar agonists attenuating jak stat mediated activation glial cells inhibiting interleukin differentiation th1 cells therefore maintain brains immune system ppar jak stat oppositely regulate dysregulation jak stat ppar signaling contributes several physiological changes leading neurological disorders including ms based view summarized combined role jak statpparsignaling ms explored potential therapeutic strategies disease improvement use pathway modulatorspmid33645493 doi102174 1874467214666210301121432,1.0
guidelines use interpretation assays monitoring autophagy 4th edition autophagy 2021 feb 81382 doi 101080 1554862720201797280 online ahead printabstractin 2008 published first set guidelines standardizing research autophagy since topic received increasing attention many scientists entered field knowledge base relevant new technologies also expanding thus important formulate regular basis updated guidelines monitoring autophagy different organisms despite numerous reviews continues confusion regarding acceptable methods evaluate autophagy especially multicellular eukaryotes present set guidelines investigators select interpret methods examine autophagy related processes reviewers provide realistic reasonable critiques reports focused processes guidelines meant dogmatic set rules appropriateness assay largely depends question asked system used moreover individual assay perfect every situation calling use multiple techniques properly monitor autophagy experimental setting finally several core components autophagy machinery implicated distinct autophagic processes canonical noncanonical autophagy implying genetic approaches block autophagy rely targeting two autophagyrelated genes ideally participate distinct steps pathway along similar lines multiple proteins involved autophagy also regulate cellular pathways including apoptosis can used specific marker bona fide autophagic responses critically discuss current methods assessing autophagy information can provide ultimate goal encourage intellectual technical innovation fieldpmid33634751 doi101080 1554862720201797280,0.0
bright spotty lesions imaging marker neuromyelitis optica spectrum disorder mult scler 2021 feb 261352458521994259 doi 101177 1352458521994259 online ahead printabstractneuromyelitis optica spectrum disorder nmosd rare inflammatory demyelinating disorder central nervous system cns aquaporin4 aqp4 antibodies serum highly specific diagnosis nmosd sensitivity remains 90 allowing diagnosis aqp4 igg seronegative disease remains crucial importance identify seronegative nmosd myelitis early first attack initiate longterm treatment will reduce future relapses disability avoid potentially harmful treatments multiple sclerosis ms years many spinal imaging features reported favour diagnosis nmosd longitudinally extensive transverse myelitis letm specific enough make diagnostic criteria aqp4 igg seronegative cases bright spotty lesions bsls defined hyperintense lesions axial t2weighted images sometimes associated t1 low signal now reported higher specificity sensitivity compared letm predicting diagnosis nmosd causes myelitis review aim highlight position bsls diagnosing nmosd well possible role prognostic factor clinical outcomepmid33635151 doi101177 1352458521994259,1.0
optic neuropathy ethambutol patient multiple sclerosis arch soc esp oftalmol 2021 feb 22s03656691 21 000198 doi 101016 joftal202012009 online ahead printabstractwe present clinical case patient developed toxic optic neuropathy due ethambutol context tuberculosis reactivation also personal history multiple sclerosis objective highlight importance making good differential diagnosis adverse effect knowing main clinical campimetric tomographic manifestations characteristics furthermore since reversibility damage still discussed literature early diagnosis essential purpose important inform patient possible symptoms carry ophthalmological examination colour tests starting treatment assess whether progressionpmid33632567 doi101016 joftal202012009,0.0
signal intensity evaluation dentate nucleus subcortical gray matter effect several administrations gadoterate meglumine multiple sclerosis clin neuroradiol 2021 feb 25 doi 101007 s00062021009956 online ahead printabstractpurpose several studies reported gadolinium deposition dentate nuclei dn globus pallidus gp associated linear gbca administrations rather macrocyclic therefore imperative evaluate assess safety cumulative administration gadoterate meglumine macrocyclic thus t1weighted images t1wi multiple sclerosis ms patients longitudinally followed 4 years retrospectively analyzedmethods study 44 patients 10 clinically isolated syndrome cis 24 relapsingremitting ms rrms 10 primaryprogressive ms ppms examined every 6 months first four scans 1year interval last two scans image processing consisted reorienting unenhanced t1wi standard space followed b1 inhomogeneity correction patientspecific template generated normalize t1wi signal intensity si segment dn subcortical gm structures structures transformed patient space order measure si region cerebellar peduncles cp semioval white matter manually delineated used reference calculate si ratios dn subcortical gm structures linear mixedeffect model finally applied longitudinally analyze si variationsresults si measurements performed structures showed significant increases cumulative gbca administrationconclusion study showed significant si increases within dn subcortical gm structures longitudinally followed ms patients even cumulative administration macrocyclic gbca gadoterate megluminepmid33630120 doi101007 s00062021009956,0.0
effects mindfulnessand acceptancebased interventions quality life coping cognition mindfulness people multiple sclerosis systematic review metaanalysis psychol health med 2021 feb 25118 doi 101080 1354850620211894345 online ahead printabstractthis systematic review metaanalysis randomized controlled trials rcts examined effects mindfulness acceptancebased interventions mabis quality life qol coping cognition mindfulness among people multiple sclerosis ms four electronic databases searched 3 july 2020 data combined randomeffects metaanalysis model eighteen rcts met eligibility criteria metaanalyses immediate posttest found moderate effects mabis qol coping attention large effect memory large effect mabis qol found followup significant effect mabis mindfulness relatively fewer studies outcomes qol found overall risk bias across included 18 rcts unclear future highquality studies followup evaluations needed support effects mabis qol coping cognition mindfulness people ms examine intervention features increase maintain effectspmid33629885 doi101080 1354850620211894345,0.0
rxr blocks nerve regeneration spinal cord injury targeting p66shc oxid med cell longev 2021 feb 10 20218253742 doi 101155 2021 8253742 ecollection 2021abstractnerve regeneration spinal cord injury regulated many factors studies found expression retinoid x receptor rxr change significantly spinal cord injury distribution rxr cells changes significantly undamaged tissues rxr distributed motor neurons cytoplasm glial cells rxr migrates nucleus surviving neurons injury indicating rxr involved regulation gene expression spinal cord injury p66shc important protein regulates cell senescence oxidative stress can induce apoptosis necrosis many cell types promoting body aging absence p66shc enhances resistance cells reactive oxygen species ros thus prolongs life found p66shc deletion can promote hippocampal neurogenesis play neuroprotective role mice multiple sclerosis verify function rxr spinal cord injury established rat t9 spinal cord transection model rxr agonist antagonist administration found rxr agonists inhibited nerve regeneration spinal cord injury rxr antagonists promoted regeneration injured neurites recovery motor function rats results showed rxr played impeding role repair spinal cord injury immunofluorescence staining showed p66shc expression upregulated neurons spinal cord injury vivo vitro colocalized rxr rxr overexpression cultured neurons promoted expression p66shc rxr interference inhibited expression p66shc using luciferase assay found rxr bind promoter region p66shc regulate expression p66shc thereby regulating nerve regeneration spinal cord injury results showed rxr inhibited nerve regeneration spinal cord injury promoting p66shc expression interference rxr p66shc promoted functional recovery spinal cord injurypmid33628383 pmcpmc7889345 doi101155 2021 8253742,1.0
amyloidoma mimicking multiple sclerosis pract neurol 2021 feb 24practneurol2020002855 doi 101136 practneurol2020002855 online ahead printno abstractpmid33627491 doi101136 practneurol2020002855,0.0
main role antibodies demyelination axonal damage multiple sclerosis cell mol neurobiol 2021 feb 24 doi 101007 s10571021010596 online ahead printabstractantibodies oxidative stress hallmarks multiple sclerosis ms lesions aimed clarify relation role ms patients investigate specificity comparing ms classical neurodegenerative diseases nd brain samples 14 ms cases 6 nd 9 controls without neurological diseases immunohistochemistry assays used detect oxidized lipids eo6 igg igm oligodendrocytes olig2 axons nf neurofilament cellular tunel axonal damage app amyloid precursor protein observe eo6 controls samples ms patients showed eo6 oligodendrocytes axons within lesions detect colocalization eo6 antibodies neither eo6 tunel app 944 tunelpositive cells normal appearing white matter also stained igg 755 igm igm igg colocalized app eo6 associated axonal damage amyotrophic lateral sclerosis als observe association antibodies cellular axonal damage nd patients ms patients showed higher number b cells plasma cells lesions meninges controls number b cells plasma cells associated presence antibodies activity lesions observed main role b lymphocytes development ms lesions antibodies contribute oligodendrocyte axonal damage ms oxidative stress associated axonal damage alspmid33625628 doi101007 s10571021010596,1.0
impact neurological disability sensory loss mindfulness practice disabil rehabil 2021 feb 2319 doi 101080 0963828820211887946 online ahead printabstractobjectives mindfulnessbased approaches increasingly recommended management medical conditions associated sensory loss absence spinal cord injury sci multiple sclerosis ms functional neurological disorder fnd yet implications undertaking practices body scanning living sensory loss considered study aimed explore impact sensory loss practice experience mindfulness qualified mindfulness teachers sci fnd msmethods eight mindfulness teachers 5 females 3 males sci fnd ms sensory loss wheelchair use recruited mindfulness teacher databases indepth semistructured interviews undertaken lasting 50 93 min interviews transcribed verbatim analysed using interpretative phenomenological analysis idiographic analyses descriptive linguistic conceptual themes completed crosscase analysesresults analyses resulted two superordinate themes 1 adopting body 2 sensation without loss themes reflected challenge overcoming initial resistance areas body sensory disruption building relationship whole body sensory awareness visualised experienced without proprioceptionconclusions mindfulness offers unique approach accepting working body paralysis sensory loss fundamental use mindfulness populations prioritisation inclusive sensory language exploring sensory absence well sensory presence cognitive emotional outcomes body scanning may uniquely elevated populations neurophysiological disorders highlighting benefits mindfulness adaptive protective selfmanagementimplications rehabilitationmindfulnessbased practices focus body sensation accessible people neurological limitationsmindfulness techniques can extended use visualisation strategies encourage nonproprioceptive awareness paralysed limbs areas body sensory lossthe language used mindfulnessbased interventions may need adapted practitioners remains inclusive people sensory loss well sensory presenceadditional care needs taken using body scans mindfulness potential exacerbate psychological distress people reduced sensory awarenesspmid33621135 doi101080 0963828820211887946,0.0
management strategies neurogenic lower urinary tract dysfunction qualitative study experiences people multiple sclerosis healthcare professionals disabil rehabil 2021 feb 22111 doi 101080 0963828820211887378 online ahead printabstractpurpose urinary symptoms highly prevalent among people ms study aimed explore experiences people ms hcps managing urinary symptoms explore views using ttns treat urinary symptomsmaterials methods audiorecorded semistructured interviews employed people ms hcps transcribed interviews exported nvivo software version 12 analyzed using reflexive approach thematic analysisresults four main themes identified wideranging negative impacts urinary symptoms limited everything else gaps urinary services somebody like sort specialized area management strategies dont go far toilet case need use one optimism ttns giving hope conclusion urinary symptoms common troublesome people ms despite prevalence many people ms continue suffer silence people ms require skilled multidisciplinary services guided clinical care pathways improve service provision address urinary symptoms hcps people ms open use ttns urinary symptoms clear preferences location duration intervention delivery implications rehabilitation urinary symptoms common troublesome people multiple sclerosis yet many continue suffer silence people multiple sclerosis lack knowledge treatment options urinary symptoms ongoing need healthcare provider education guidelines screening managing urinary symptoms people ms role specialist urinary service providers hcps people ms open use ttns urinary symptomspmid33617371 doi101080 0963828820211887378,0.0
novel coronavirus infection covid19 nervous system involvement mechanisms neurological disorders clinical manifestations organization neurological care neurosci behav physiol 2021 feb 1818 doi 101007 s11055021010500 online ahead printabstractthe new coronavirus sarscov2 disease causes covid19 involves respiratory system damage can also lead disorders central peripheral nervous system well muscular system article presents published data observations course neurological disorders covid19 patients relationship severity covid19 severity frequency neurological manifestations severe neurological disorders mostly seen severe cases covid19 include acute cerebrovascular accidents acva acute necrotizing encephalopathy guillainbarr syndrome factors potentially complicating course covid19 increasing development neurological complications include arterial hypertension diabetes mellitus chronic cardiac respiratory system diseases questions possible effects human coronaviruses course chronic progressive neurological diseases addressed using multiple sclerosis ms example discuss management patients acva ms depending risk developing coronavirus infectionpmid33619413 pmcpmc7889305 doi101007 s11055021010500,0.0
functional neurological disorder multiple sclerosis systematic review misdiagnosis clinical overlap j neurol 2021 feb 21 doi 101007 s00415021104366 online ahead printabstractmultiple sclerosis ms functional neurological disorder fnd diagnostically challenging conditions can present similar symptoms systematically reviewed literature identify patients ms misdiagnosed fnd patients fnd misdiagnosed ms reports patients conditions addition fnd included studies patients functional psychiatric disorders caused symptoms leading investigation diagnosis ms different context likely labeled fnd review suggests ms one common causes misdiagnosis fnd vice versa discuss clinical errors appear result misdiagnoses overreliance psychiatric comorbidity making diagnosis fnd overreliance neuroimaging diagnosis ms practical ways avoid comorbidity two conditions also likely common poorly studied adds complexity diagnosis treatment patients ms fnd misdiagnosis comorbidity landscape emerging evidencebased treatments ms fnd issues clinical importance care patients also treatment trials especially ms fnd hidden confounderpmid33611631 doi101007 s00415021104366,0.0
menopause modify disability trajectories longitudinal cohort women cis ms followed disease onset eur j neurol 2021 feb 20 doi 101111 ene14782 online ahead printabstractobjective evaluate effect menopause disability accumulation women followed clinically isolated syndrome cis methods examined longitudinal changes edss cis last followup women belonging barcelona cis prospective cohort followed menopausal transition analysis based 13 718 edss measurements average 28 edss per patient differences edss trajectories menopausal nonmenopausal women controlling age disease duration evaluated performed two sensitivity analyses women confirmed ms experiencing early menopauseresults 764 eligible women 496 65 responded questionnaire 74 149 reached menopause followup find significant inflection point edss trajectories around menopause slope change 0009 95ci 0066 0046 annual increase edss complete course disease significantly higher menopausal women 0049 ic 95 0026 0074 versus nonmenopausal 0019 ic 95 0008 0031 interaction pvalue 0025 difference lost controlling age disease duration edss annual increase 0059 95 ci 0025 0094 vs 0038 ic 95 0021 0057 respectively interaction pvalue 0321 inflection point detected analysis restricted women confirmed ms earlier menopauseconclusion menopause associated increased risk disability cis population considering edss trajectories throughout course disease together age disease durationpmid33609298 doi101111 ene14782,0.0
global transcriptome profiling peripheral blood mononuclear cells identifies dysregulation immune processes individuals radiologically isolated syndrome abstractthe presence brain spinal white matter lesions typical multiple sclerosis ms asymptomatic individuals known radiologically isolated syndrome ris taking account ris patients high risk ms development understanding mechanisms underlying pathogenesis great importance order investigate risspecific transcription signature performed highthroughput rnasequencing peripheral blood mononuclear cells pbmcs 8 ris patients 8 age sexmatched healthy controls identified 57 differentially expressed genes degs levels differed 2 times comparing ris patients healthy controls fdr p value 005 gene ontology enrichment analysis biological process category revealed 16 signaling pathways significantly overrepresented identified degs significant changes gene expression pbmcs ris patients occur pathways involved regulation immune response cytokine chemokine signaling cytokine production leukocyte migration general analyzing global transcriptome demonstrated dysregulation immune processes pbmcs ris patients confirming current assumption ris represents preclinical stage subclinical form ms,0.0
feasibility theoryinformed mobile app changing physical activity youth multiple sclerosis abstractbackgroundyouth multiple sclerosis ms high levels disease activity depression fatigue lower moderate vigorous physical activity pa pa participation associated lower disease activity depression fatigue well higher selfefficacy goal setting decreased barriers later constructs may targeted intervention program behavior change intervention must account disease rarity geographical proximity time constraints limit feasibility accessibility sustainability implementing pa intervention youth ms developed theoryinformed mobileapp based pa promotion program address barriers active teens multiple sclerosis atomic herein report feasibility delivering intervention youth msobjective determine feasibility delivering atomic program youth msmethodsfifteen youth ms 13f 16612 years followed hospital sick children enrolled atomic intervention participants underwent standard clinical evaluation exercise test determine cardiorespiratory fitness 7day pa monitoring accelerometer completed standardized depression fatigue questionnaires baseline postintervention social cognitive scales related selfefficacy selfmanagement goal setting perceived barriers outcome expectancy social support completed baseline six 12weeks 12week mobile app pa intervention informed social cognitive theory sct included individualized pa coaching pa selfmonitoring fitbit goal setting social support ms specific educational modules feasibility defined 1 meeting recruitment target 15 participants within oneyear period 2 completion 80 study related questionnaires testing 3 dropout rate less 20 4 adherence atomic intervention program components 80 fitbit wear pa coaching calls modules resultsfrom march 2018 april 2019 53 youth approached agreed participate 15 28 13 15 participants completed intervention 36 possible 39 coaching calls 92 3 possible phone calls per participant 89 wear adherence fitbitcharge2 data mean75 166 days 84 days 5 12 42 modules completed average 84 sd 40 range740 176 increase fitbit steps first week intervention observed pa level accelerometry 12weeks aerobic fitness depression fatigue unchanged sct scales indicated increase social support friends 067points t27 pholm004 decrease outcome expectancy 27 t30 pholm003 differences selfefficacy selfmanagement perceived barriers post interventionconclusionsour results indicate atomic program feasible delivery youth ms future work needed understand best implement element sct added features mobileapp evaluate individual components sct mediate change pa behaviours youth ms,0.0
temporal patterns microglial activation white matter following experimental mild traumatic brain injury systematic literature review abstractmild traumatic brain injuries mtbis prevalent form injury can result persistent neurological impairments microglial activation become increasingly recognized key process regulating pathology white matter wide range brain injury disease contexts white matter damage known major contributor impairments follow mtbi microglia rightfully become common target investigation development mtbi therapies biomarkers recent work demonstrated efficacy microglial manipulation therapeutic intervention following injury disease highly timesensitive emphasizing importance advancing understanding dynamics postmtbi microglial activation onset resolution current reporting microglial activation experimental studies mtbi nonstandardized limited ability identify concrete patterns postmtbi microglial activation time review examine preclinical studies mtbi report microglial activation white matter regions summarize current understanding patterns specifically summarize timecourses postmtbi microglial activation white matter regions brain identify factors influence activation examine temporal relationship microglial activation postmtbi assessments compare relative sensitivities various methods detecting microglial activation lack replicated experimental conditions limited extent conclusions can confidently drawn find microglia activated wide range timecourses following mtbi microglial activation longlasting outcome mtbi may resolve typical postmtbi assessments exception measuring oligodendrocyte lineage cell integrity identify several understudied parameters postmtbi microglial activation white matter inclusion female subjects review summarizes current understanding progression microglial activation white matter structures following experimental mtbi offers suggestions important future research directions,0.0
improve indepth immunological risk assessment optimize geneticcompatibility clinical outcomes child adolescent recipients parental donor kidney transplants protocol inception study background parental donor kidney transplantation common treatment option children adolescents kidney failure emerging data observational studies reported improved short mediumterm allograft outcomes recipients paternal compared maternal donors inception study aims identify potential differences immunological compatibility maternal paternal donor kidneys ascertain affects kidney allograft outcomes children adolescents kidney failuremethodsthis longitudinal observational study will recruit kidney transplant recipients aged 18 years received parental donor kidney transplant across 4 countries australia new zealand united kingdom netherlands 1990 2020 high resolution human leukocyte antigen hla typing recipients corresponding parental donors will undertaken provide indepth assessment immunological compatibility primary outcome composite de novo donorspecific antihla antibody dsa biopsyproven acute rejection allograft loss 60months posttransplantation secondary outcomes de novo dsa biopsyproven acute rejection acute chronic antibody mediated rejection chronic allograft damage index cadi score 1 allograft biopsy posttransplant allograft function proteinuria allograft loss using principal component analysis cox proportional hazards regression modelling will determine associations defined sets immunological clinical parameters may identify risk stratification primary secondary outcome measures among young people accepting parental donor kidney transplantation study design will allow us specifically investigate relative importance accepting maternal compared paternal donor families deciding best option donationdiscussionthe inception study findings will explore potentially differential immunological risks maternal paternal donor kidneys transplantation among children adolescents study will provide evidence base underpinning selection parental donor order achieve best projected longterm kidney transplant overall health outcomes children adolescents recognized vulnerable populationtrial registrationthe inception study registered australian new zealand clinical trials registry trial registration number actrn12620000911998 14th september 2020,0.0
targeted cognitive game training enhances cognitive performance multiple sclerosis patients treated interferon beta 1a background prevention cognitive decline multiple sclerosis ms major importance explored effect 6 months computerized game training program cognitive performance ms patients mild cognitive impairmentmethodsthis singlecenter randomized prospective study enrolled study 100 eligible ms patients treated interferonbeta1a rebif mild cognitive impairment either executive function information processing speed patients randomized 11 either use cognitive games platform happyneuron hn receive intervention executive function information processing speed scores measured 3 6 months baseline evaluate effect game training cognitive scoresresultsin executive function information processing speed game training group showed significant improvement 3 6 months nontraining group showed mild deterioration domains 3 months deterioration became significant 6 months executive function furthermore 6 months percent patients training group improved remained stable cognitive domains significantly higher compared nontraining groupconclusionsour findings suggest cognitive game training beneficial effect cognitive performance ms patients suffering mild cognitive impairment evaluation required assess longevity effect nonetheless recommend ms patients engaged cognitive gaming practice part holistic approach treating condition,0.0
efficacy intravenous immunoglobulin autoimmune neurological diseases literature systematic review metaanalysis autoimmun rev 2021 dec 14103019 doi 101016 jautrev2021103019 online ahead printabstractbackground corticosteroids firstline treatment several common autoimmune neurological diseases therapeutic approaches including intravenous immunoglobulin ivig plasmapheresis shown mixed results patient improvementobjective compare efficacy ivig administration corticosteroids plasmapheresis placebo autoimmune neurological diseases like guillainbarr syndrome myasthenia gravis chronic inflammatory demyelinating polyneuropathy optic neuritis multiple sclerosismethods systematic review performed databases pubmed medline embase cochrane controlled randomized studies comparing efficacy ivig placebo plasmapheresis glucocorticoid administration selected studies reporting number patients improved treatment included irrespective language publication year total 23 reports included metaanalysis studyresults metaanalysis showed beneficial effect ivig administration patient improvement placebo 279 ci 95 140555 p 001 meanwhile ivig administration showed virtually identical effects plasmapheresis 083 ci 95 045155 p 001 finally significant differences found efficacy ivig glucocorticoid administration 098 cl 95 058168 p 013 conclusion ivig can regarded viable therapeutic approach either first secondline therapy adjuvant therapy autoimmune neurological diseasespmid34920107 doi101016 jautrev2021103019,1.0
circ_0000518 promotes macrophage#x2f microglia m1 polarization via fus#x2f camkkbeta#x2f ampk pathway aggravate multiple sclerosis neuroscience 2021 dec 14s03064522 21 006369 doi 101016 jneuroscience202112012 online ahead printabstractevidence shown circ_0000518 upregulated peripheral multiple sclerosis ms patients suggesting may play important role progression ms however specific mechanism ms progression unclear study human microglial clone 3 hmc3 cells treated 100 ng ml lps 24 h short hairpin rna hsa_circ_0000518 shhsa_circ_0000518 transfected cells incubated 48 h found increased circ_0000518 expressions increased apoptosis oxidative stress increased m1 phenotype marker expression decreased m2 phenotype marker expression cells interfering circ_0000518 expression reversed effect lps hmc3 cells online bioinformatics database analysis indicated fus rna binding protein circ_0000518 next observed increased fus expression lps treated hmc3 cells interfering fus expression reduced lps triggered apoptosis oxidative stress decreased m1 phenotype marker expression promoted m2 phenotype marker expression mechanistic studies revealed interfering fus promoted polarization hmc3 cells m1 phenotype m2 phenotype via activation camkk ampkpgc1 pathway whereas promoting effect counteracted sto609 experimental autoimmune encephalomyelitis eae mouse model observed circ_0000518 knockdown reduced circ_0000518 fus expression brain spinal cord tissues reduced neurological scores mice alleviated inflammatory cell infiltration cns summarily study identified circ_0000518 promotes macrophage microglial m1 polarization fus camkk ampk pathway aggravates mspmid34920022 doi101016 jneuroscience202112012,0.0
paraneoplastic myelopathy amphiphysin autoantibodies lobular breast carcinoma situ j neurol sci 2021 dec 11 432120086 doi 101016 jjns2021120086 online ahead printno abstractpmid34920159 doi101016 jjns2021120086,0.0
optimized validated protocol inducingchronic experimental autoimmune encephalomyelitis c57bl#x2f 6j mice j neurosci methods 2021 dec 14109443 doi 101016 jjneumeth2021109443 online ahead printabstractbackground myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis eae commonly used animal model multiple sclerosis however variations induction protocol can affect eae progression may reduce comparability dataoptimized method present study investigated influence different components used eae induction c57bl 6j mice disease progression present study mog3555induced chronic eae c57bl 6j mice applied model challenge optimal pertussis toxin ptx dosing considering variations batch potencyresults demonstrate dosage ptx adjusted potency influences eae development dosedependent manner data show protocol considers ptx potency c57bl 6j mice consistently develop symptoms eae mice show typical chronic course symptom onset 105 108 days maximum severity around day 16 postimmunization followed mild remission symptomscomparison existing methods previously studies reveal alterations ptx dosing directly modify eae progression present study highlights ptx batches differ potency resulting inconsistent eae induction also provide clear protocol allows reduction number mice used eae experiments maintaining consistent resultsconclusion higher standards comparability reproducibility needed ensure maximize generation reliable eae data specifically consideration ptx potency method establishing consistent eae pathogenesis improved animal welfare standards reduction mice used experimentation can achievedpmid34920025 doi101016 jjneumeth2021109443,1.0
comparative effectiveness costeffectiveness natalizumab fingolimod patients inadequate response diseasemodifying therapies relapsingremitting multiple sclerosis united kingdom pharmacoeconomics 2021 dec 18 doi 101007 s40273021011066 online ahead printabstractbackground patients highly active relapsingremitting multiple sclerosis inadequately responding firstline therapies interferonbased therapies glatiramer acetate dimethyl fumarate teriflunomide known collectively bracetd often switch natalizumab fingolimodobjective aim estimate comparative effectiveness switching natalizumab fingolimod within bracetd using realworld data evaluate costeffectiveness switching natalizumab versus fingolimod using united kingdom uk thirdparty payer perspectivemethods realworld data obtained msbase patients relapsing bracetd year switching natalizumab fingolimod within bracetd threewaymultinomialpropensityscorematched cohorts identified comparisons treatment groups conducted annualised relapse rate arr 6monthconfirmed disability worsening cdw6m improvement cdi6m results applied costeffectiveness model lifetime horizon using published markov structure health states based expanded disability status scale model parameters obtained uk ms survey 2015 published literature publicly available uk sourcesresults msbase analysis found significant reduction arr rate ratio rr 064 95 confidence interval ci 057072 p 0001 increase cdi6m hazard ratio hr 167 95 ci 130215 p 0001 switching natalizumab compared bracetd switching fingolimod reduction arr rr 091 95 ci 081103 p 0133 increase cdi6m hr 130 95 ci 099172 p 0058 compared bracetd significant switching natalizumab associated significant reduction arr rr 070 95 ci 062079 p 0001 increase cdi6m hr 128 95 ci 101162 p 0040 compared switching fingolimod evidence difference cdw6m found treatment groups natalizumab dominated higher qualityadjusted lifeyears qalys lower costs fingolimod basecase costeffectiveness analysis 0453 higher qalys 20 843 lower costs per patient results consistent across sensitivity analysesconclusions novel realworld analysis suggests clinical benefit therapy escalation natalizumab versus fingolimod based comparative effectiveness results translating higher qalys lower costs uk patients inadequately responding bracetdpmid34921350 doi101007 s40273021011066,0.0
imaging features distinguish aqp4positive nmosd ms disease onset retrospective analysis singlecenter cohort eur j radiol 2021 nov 23 146110063 doi 101016 jejrad2021110063 online ahead printabstractpurpose compare diagnostic performance imaging criteria differentiate aqp4+ neuromyelitis optica spectrum disorders nmosd multiple sclerosis ms disease onset followup fu methods retrospectively analyzed mri scans defined first 60 days patientreported symptom onset 10 aqp4+nmosd 25 time mri matched relapsingremitting ms patients monocentric cohortresults matthews criteria met 20 aqp4+nmosd patients vs 33 fu 96 rrms patients vs100 fu specificity sp sensitivity se thus high timepoints spdo 96 spfu100 sedo 80 sefu 67 similar area curve auc values 88 95 ci 74100 fu 83 95 ci 67100 cacciaguerra criteria met 90 aqp4+nmosd patients vs 889 fu 24 rrms patients vs 14 fu spdo 87 spfu 86 sedo 90 sefu 89 similar auc values 88 95 ci 7698 fu 87 95 ci 7498 conclusions diagnostic mri criteria developed data acquired years disease onset study demonstrates high applicability earliest disease stages thus emphasising valuable use clinical practicepmid34922119 doi101016 jejrad2021110063,0.0
simplified stance limb kinetics patterns revealed gait initiation early stage multiple sclerosis clin biomech bristol avon 2021 dec 13 91105549 doi 101016 jclinbiomech2021105549 online ahead printabstractbackground although patients early stage multiple sclerosis ms commonly complain balance gait impairments troubles remain misunderstood objective compare body kinematics lower limb kinetics gait initiation patients ms edss score 4 healthy participantsmethods sixteen patients ms median edss score 25 04 disease duration 74 42 years well 16 healthy participants included 3d motion analysis performed gait initiation calculate spatiotemporal kinematic kinetic parametersfindings center pressure position beginning gait initiation anterior p 002 patients ms healthy participants kinetic parameters stance limb highly affected patients ms compared healthy participants gait initiation net muscular moments joint significantly different anticipatory postural adjustment phase smoother variations patients ms compared healthy participantsinterpretation early stage ms strongly affects motor modulation stance limb kinetics anticipatory postural adjustment gait initiation without alteration execution phase net muscular moments sensitive detecting unobservable balance impairments can used assess disease progression early stage results suggest early rehabilitation programs aimed improving motor modulation flexibility gait initiation implementedpmid34922096 doi101016 jclinbiomech2021105549,0.0
burden rare coding variants italian cohort familial multiple sclerosis j neuroimmunol 2021 nov 5 362577760 doi 101016 jjneuroim2021577760 online ahead printabstractbackground multiple sclerosis ms chronic inflammatory neurodegenerative demyelinating disease central nervous system complex heterogeneous disease caused combination genetic environmental factors can cluster familiesobjective evaluate genelevel aggregate contribution predicted damaging lowfrequency rare variants ms risk multiplex familiesmethods performed whole exome sequencing wes 28 multiplex ms families least 3 ms cases 81 affected 42 unaffected relatives 38 unrelated healthy controls genebased burden test performed focusing two sets candidate genes literaturedriven selection ii datadriven selectionresults identified 11 genes enriched predicted damaging lowfrequency rare variants ms compared healthy individuals among ubr2 dst two genes strongest enrichment p 5 104 3 104 respectively interestingly enough association signal ubr2 driven rs62414610 present 25 analysed familiesconclusion despite limitations one first studies evaluating aggregate contribution predicted damaging lowfrequency rare variants ms families using wes data replication effort independent cohorts warranted validate findings evaluate role identified genes ms pathogenesispmid34922125 doi101016 jjneuroim2021577760,1.0
physical telerehabilitation improves quality life patients multiple sclerosis stud health technol inform 2021 dec 15 284384388 doi 103233 shti210752abstractthe purpose study investigate effect physical telerehabilitation quality life qol patients multiple sclerosis pwms randomized controlled trial pwms groups received homebased individualized exercise plan based physical therapy exam pwms intervention group guided telerehabilitation system following exercise program daily basis whereas pwms control group received periodic newsletters diseasespecific qol assessed msqol54 survey baseline end 3month rehabilitation program among msqol subscales mean subscore values pain cognitive function control intervention groups significantly different demonstrated oneway anova pain f 4301 p 0044 cognitive function f 5053 p 0030 results demonstrated positive effects physical telerehabilitation ms symptoms qol development approaches promoting continuous participation telerehabilitation pwms warrantedpmid34920553 doi103233 shti210752,0.0
natural history optic neuritis multiple sclerosis pediatr engl ed 2021 dec 14s23412879 21 002040 doi 101016 janpede202011012 online ahead printno abstractpmid34920972 doi101016 janpede202011012,0.0
new diagnosis multiple sclerosis setting mrna covid19 vaccine exposure j neuroimmunol 2021 dec 9 362577785 doi 101016 jjneuroim2021577785 online ahead printabstractbackground multiple sclerosis ms onset setting acute sarscov2 virus infection reported reactivation ms following nonmrna covid19 vaccination noted three reports newly diagnosed ms following exposure mrna covid19 vaccine association determined causal latent central nervous system demyelinating disease may unmask setting infection systemic inflammatory response report series 5 cases newly diagnosed ms following recent exposure mrna covid19 vaccines latency vaccination initial presentation varied neurological manifestations clinical course appeared typical ms including response high dose steroids 4 cases additional need plasmapheresis one caseconclusion acute neurological deficits setting recent mrna covid19 vaccine administration may represent new onset multiple sclerosispmid34922126 doi101016 jjneuroim2021577785,1.0
humoral cellular immunity convalescent covid19 people multiple sclerosis treated ofatumumab j neuroimmunol 2021 dec 13 362577788 doi 101016 jjneuroim2021577788 online ahead printabstractobjectives report clinical outcome development humoral tcell mediated immunity convalescent covid19 people multiple sclerosis pwms treated ofatumumab alithios study single centermethods testing sarscov2 igg antibodies performed two occasions least three months apart two testing second antibody testing interferon elispot used assess cellular immunityresults four subjects mild covid19 infection without sequelae subjects except subject 2 covid19 confirmed pcr subjects 1 2 4 normal levels igm igg without measurable counts cd19 cells prior covid19 subject 3 administered last dose ofatumumab 24 days prior covid19 symptoms gap 28 weeks ofatumumab application beforehand due low igm levels subject 4 received covid19 vaccinations second testing second testing tcell immunity testing performed subjects cd19 depleted measurable levels sarscov2 igg antibodies subject 3 first second sarscov2 titer 118 u ml 250 u ml respectively three pwms showed t cell immunity sarscov2 quotient basal spots divided interferon secreting spot forming units 4 8 147 si subjects 1 2 3 respectively 3 considered reactive conclusion antibody response observed pwms cd19+ lymphocyte depleted t cell immunity sarscov2 observed three pwms treated ofatumumabpmid34922128 doi101016 jjneuroim2021577788,0.0
characterisation trim46 autoantibodyassociated paraneoplastic neurological syndrome j neurol neurosurg psychiatry 2021 dec 17jnnp2021326656 doi 101136 jnnp2021326656 online ahead printabstractobjectives report expanded neurological presentations oncological associations tripartite motifcontaining protein 46 trim46 igg seropositive patientsmethods archived sera cerebrospinal fluid csf evaluated tissuebased immunofluorescence assay identify patients identical axon initial segment ais specific staining pattern phage immunoprecipitation sequencing phipseq used identify putative autoantigenresults igg serum 17 csf 16 25 patients yielded unique aisspecific staining murine central nervous system cns tissue autoantibody specific trim46 identified phipseq autoantigen specificity confirmed transfected cos7 cellbased assay clinical information available 22 trim46igg seropositive patients fifteen female 68 median age 67 years range 2587 fifteen 68 patients presented subacute cerebellar syndrome six isolated nine cns accompaniments encephalopathy three brainstem signs two myelopathy two parkinsonism one phenotypes included limbic encephalitis three encephalopathy without seizures two myelopathy two eighteen 82 cancer neuroendocrine carcinomas 9 pancreatic 3 smallcell lung 4 oesophagus 1 endometrium 1 adenocarcinomas 6 lung 2 ovarian 2 endometrial 1 breast 1 sarcoma 2 gastrointestinal tumour 1 neurological symptoms three followed immune checkpoint inhibitor ici administrationconclusions study supports trim46igg biomarker paraneoplastic cns disorders expands neurological phenotypes oncological icirelated adverse event associationspmid34921120 doi101136 jnnp2021326656,0.0
glymphatic system impairment multiple sclerosis relation brain damage disability brain 2021 dec 17awab454 doi 101093 brain awab454 online ahead printabstractrecent evidences showed existence central nervous system waste clearance system defined glymphatic system glymphatic abnormalities described several neurodegenerative conditions including alzheimers parkinsons disease glymphatic function thoroughly explored multiple sclerosis neurodegenerative processes intermingled inflammatory processes aimed investigate glymphatic system function multiple sclerosis evaluate association clinical disability disease course demyelination neurodegeneration quantified using different mri techniques retrospective study enrolled 71 multiple sclerosis patients 49 relapsingremitting 22 progressive multiple sclerosis 32 age sex matched healthy controls subjects underwent neurological mri assessment including highresolution t1 t2 double inversion recovery sequences diffusion susceptibility weighted imaging calculated diffusion along perivascular space index proxy glymphatic function cortical deep gray matter volume white cortical gray matter lesion volume normal appearing white matter microstructural damage multiple sclerosis patients showed overall lower diffusion along perivascular space index vs healthy controls estimated mean difference 009 p 001 relapsingremitting progressive multiple sclerosis patients lower diffusion along perivascular space index vs healthy controls estimated mean difference 006 p 004 relapsingremitting 019 p 0001 progressive multiple sclerosis patients progressive multiple sclerosis patients showed lower diffusion along perivascular space index vs relapsingremitting multiple sclerosis patients estimated mean difference 009 p 003 multiple sclerosis patients lower diffusion along perivascular space index associated severe clinical disability r 045 p 0001 longer disease duration r 037 p 0002 interestingly detected negative association diffusion along perivascular space index disease duration first 413 years disease course r 038 p 004 without association thereafter 34 years disease duration lower diffusion along perivascular space index associated higher white r 036 p 0003 cortical r 041 p 0001 lesion volume severe cortical r 030 p 0007 deep r 042 p 0001 gray matter atrophy reduced fractional anisotropy r 042 p 0001 increased mean diffusivity r 045 p 0001 normalappearing white matter results suggest glymphatic system impaired multiple sclerosis especially progressive stages impaired glymphatic function associated measures demyelination neurodegeneration reflects severe clinical disability findings suggest glymphatic impairment may pathological mechanism underpinning multiple sclerosis dynamic interplay pathological substrates disease deserves investigationpmid34919648 doi101093 brain awab454,1.0
de novo pathogenic variant setx causes rapidly progressive neurodegenerative disorder early childhoodonset severe axonal polyneuropathy abstractpathogenic variants setx cause two distinct neurological diseases lossoffunction recessive disorder ataxia oculomotor apraxia type 2 aoa2 dominant gainoffunction motor neuron disorder amyotrophic lateral sclerosis type 4 als4 identified two unrelated patients de novo c23c t pthr8met variant setx presenting earlyonset severe polyneuropathy rare private gene variation often difficult link genetic neurological disease dna sequence alone used transcriptional network analysis functionally validate patients severe de novo setxrelated neurodegenerative disorder weighted gene coexpression network analysis wgcna used identify diseaseassociated modules two different als4 mouse models compared confirmed als4 patient data derive als4specific transcriptional signature wgcna whole blood rnasequencing data patient pthr8met setx variant compared als4 control patients determine signature used identify affected patients wgcna identified overlapping diseaseassociated modules als4 mouse model data als4 patient data mouse als4 diseaseassociated modules associated aoa2 disease modules confirming distinct diseasespecific signatures expression profile patient carrying c23c t pthr8met variant significantly associated human mouse als4 signature confirming relationship setx variant disease similar clinical presentations two unrelated patients de novo pthr8met variant functional data provide strong evidence pthr8met variant pathogenic distinct phenotype expands clinical spectrum setxrelated disorders,0.0
regulated cell death discovery features implications neurodegenerative diseases abstractregulated cell death rcd ubiquitous process living organisms essential tissue homeostasis restore biological balance stress decades various forms rcd reported increasingly found involve human pathologies clinical outcomes focus five highprofile forms rcd including apoptosis pyroptosis autophagydependent cell death necroptosis ferroptosis cumulative evidence supports different features various pathways also extensive crosstalks modes cell death understanding rcd pathway evolution development physiology disease continues improve review updated classification rcd discovery features processes prominent focus will placed key mechanisms rcd critical role neurodegenerative disease video abstract graphical abstract,0.0
one prick done mixedmethods exploratory study intramuscular injection heroinassisted treatment background intramuscular im injection drugs associated high rates injectingrelated injuries diseases however little known role route administration heroinassisted treatment aim study determine prevalence im diacetylmorphine administration associated complications well explore patients views opinions topic underlying reasons practicemethodsthe research site swiss outpatient treatment centre specialised heroinassisted treatment conducted indepth interviews two patients intramuscularly inject diacetylmorphine interviews analysed qualitatively emerging themes used develop 38item questionnaire im injections offered questionnaire patients treatment centreresultsfive main themes emerged indepth interviews poor venous access side effects subjective effects procedure im injection consideration alternatives im themes covered rationale using route administration complications subjective effects im diacetylmorphine hygiene safety measures well alternative routes administration fiftythree patients filled questionnaire lifetime prevalence im injections 604 n 32 344 n 11 patients stated im injection primary route administration participant reported using im route street drugs main reason im injections poor vein access reasons given time saving less risk injuries complications included induration muscle tissue pain whereas severe complications like thrombosis infections injection site reported much less oftenconclusionas population opioiddependent individuals aging deterioration access veins likely increase frequency im injecting will equally increase even though data show im injection diacetylmorphine clinical setting common practice appears relatively safe research alternative routes administration needed provide potentially less harmful alternative routes administration heroinassisted treatment,0.0
interferon beta1a treatment promotes sarscov2 mrna vaccine response multiple sclerosis subjects abstractbackgroundseveral concerns exist immunogenicity sarscov2 vaccines multiple sclerosis ms subjects due immunomodulating disease modifying therapies dmts report comparison humoral response bnt162b2mrna coronavirus covid 19 vaccine immunological phenotype cohort 125 ms subjects undergoing different dmts history sarscov2 infectionmethodswe collected serum blood samples first day vaccine t0 21 days second vaccine dose t1 125 ms subjects undergoing eight different dmts sera tested using elecsys antisarscov2igg assay detection igg antibodies sarscov2 spike protein antispike igg titres ms subjects compared 24 age sexmatched healthy controls hc percentage absolute number b t lymphocytes evaluated cytofluorimetric analysis study cohortresultswhen compared sarscov2 igg levels hc n24 median 1089 iqr 65251625 u ml observed increased secretion sarscov2 igg interferonbeta 1a ifn treated ms subjects n22 median 1916 iqr 10242879 u ml impaired humoral response ms subjects undergoing cladribine clad n10 median 3969 iqr 37527909 u ml fingolimod fty n19 median 79 iqr 481476 u ml ocrelizumab ocre n15 median 067 iqr 0459 u ml treatment moreover analysis geometric mean titre ratio gmtr different dmtnulls groups ms subjects revealed compared ifntreated ms subjects intrinsic antibody production impaired teriflunomide teri natalizumab nat clad fty ocre preserved dmf gatreated ms subjectsconclusionhumoral response bnt162b2mrnavaccine increased ifntreated ms subjects clearly blunted clad fty ocre treatment suggests dmts key role protection sarscov2 related disease complication ms subjects underlying novel aspect considered selection appropriate therapy covid19 pandemic,0.0
can adults cerebral palsy perform benefit ballistic strength training improve walking outcomes mixed methods feasibility study background power bursts hips ankle plantar flexors prerequisites walking propulsion however power bursts reduced gait persons cerebral palsy cp mainly ankle plantar flexors hence task specific training ballistic strength training suggested increase muscle power walking investigated adults cp therefore aim investigate adults cp perform benefit ballistic strength training improve walking evaluated physical measures selfreported measures interviewsmethodsin mixed methods feasibility study eight ambulatory adults aged 2456 spastic cp conducted ballistic strength training glideboard targeting ankle plantarflexors two times week eight weeks feasibility training assessed objectives described orsmond cohn intervention physical measures 6minute walk test eightitem highlevel mobility assessment tool selfreported measures patient global impression change numeric pain rating scale fatigue impact severity selfassessment walk12 collected intervention semistructured interviews explored experiences training resultsthe participants experienced training ankle plantar flexor relevant reported took four weeks coordinate exercises successfully although observed changes physical performance measures participants reported improvements felt steadier standing walking hoppingconclusionthis study demonstrated ballistic strength training feasible suitable adults cp however guidance long 4 weeks familiarization time reported necessary master exercises participants reported selfexperienced improvements although physical performance measures improved thus prolonged intervention may required perceived physical improvements emerge also outcome measures sensitive power output remains investigated,0.0
immunogenicity profile african green monkeys vaccine candidate based mutated form human interleukin15 background interleukin il 15 proinflammatory tcell growth factor overexpressed several autoimmune diseases rheumatoid arthritis initial strategy neutralize increased levels il15 consisted vaccine candidate based recombinant modified human il15 mhil15 mixed alum adjuvant previous study nonhuman primates macaca fascicularis shown vaccination induces neutralizing antibodies native il15 without affecting animal behavior clinical status percentage il15dependent cell populations however mhil15 used antigen active il2dependent cytotoxic tcell line ctll2 hinder therapeutic application current article evaluated immunogenicity african green monkeys vaccine candidate based il15 mutant d8sq108s inactive form human il15resultsil15 d8sq108s inactive ctll2 bioassay able competitively inhibit biological activity human il15 immunization 200 g il15 mutant combined alum elicited antiil15 igg antibodies second third immunizations median values antiil15 antibody titers slightly higher generated animals immunized 200 g mhil15 highest antibody titers induced third immunization monkeys vaccinated 350 g il15 d8sq108s addition sera immunized animals inhibited biological activity human il15 ctll2 cells maximum neutralizing effect observed third immunization sera monkeys vaccinated highest dose il15 mutant sera also inhibited proliferative activity simian il15 ctll2 bioassay affect il2induced proliferation aforementioned tcell line finally observed vaccination neither affects animal behavior general clinical parameters immunized monkeysconclusionimmunization inactive il15 d8sq108s mixed alum generated neutralizing antibodies specific human il15 african green monkeys based fact current vaccine candidate effective one based biologically active mhil15 treating autoimmune disorders involving uncontrolled overproduction il15,0.0
pdia3 inhibits mitochondrial respiratory function brain endothelial cells c elegans stat3 signaling decreases survival ogd background protein disulfide isomerase a3 pdia3 also named grp58 er60 erp57 conserved across species mediates protein folding endoplasmic reticulum pdia3 reportedly chaperone stat3 however role pdia3 regulating mitochondrial bioenergetics stat3 phosphorylation serine 727 s727 describedmethodsmitochondrial respiration compared immortalized human cerebral microvascular cells cmec wild type null pdia3 whole organism c elegans wt null pdi3 worm homologue mitochondrial morphology cell signaling pathways pdia3 wt cells assessed pdia3 cells subjected oxygenglucose deprivation ogd determine effects pdia3 cell survival injuryresultswe show pdia3 gene deletion using crisprcas9 cultured cmecs leads increase mitochondrial bioenergetic function c elegans gene deletion rnai knockdown pdi3 also increased respiratory rates confirming conserved role gene regulating mitochondrial bioenergetics pdia3 bioenergetic phenotype reversed overexpression wt pdia3 cultured pdia3 cmecs pdia3 sirna knockdown caused increase phosphorylation s727 residue stat3 known promote mitochondrial bioenergetic function increased respiration pdia3 cmecs reversed stat3 inhibitor pdia3 cmecs mitochondrial membrane potential reactive oxygen species production mitochondrial mass increased suggesting increased mitochondrial bioenergetic capacity finally pdia3 cmecs resistant oxygenglucose deprivation stat3 inhibition reduced protective effectconclusionswe discovered novel role pdia3 suppressing mitochondrial bioenergetic function inhibiting stat3 s727 phosphorylation,0.0
association helicobacter pylori infection risk metabolic syndrome insulin resistance updated systematic review metaanalysis background conflicting results recent studies association helicobacter pylori h pylori infection risk insulin resistance metabolic syndrome explored need updated metaanalysis issue therefore systematic review aimed estimate pooled effect h pylori infection risk insulin resistance metabolic syndromemethodsto identify casecontrol studies cohort studies evaluating association h pylori infection insulin resistance metabolic syndrome comprehensive literature search performed international databases including medline pubmed web sciences scopus embase cinhal january 1990 january 2021 used odds ratio 95 confidence interval quantify effect casecontrol studies risk ratio 95 ci effect cohort studiesresults22 studies 206 911 participants included metaanalysis pooled estimate odds ratio h pylori infection metabolic syndrome casecontrol studies 119 95 ci 105135 i2 0 cohort studies pooled risk ratio 131 95 ci 113151 i2 0 besides casecontrol studies showed pooled odds ratio 154 95 ci 119198 i2 688 association h pylori infection insulin resistanceconclusionin metaanalysis results showed possibility metabolic syndrome insulin resistance case h pylori infection,0.0
pandemicassociated mental health changes youth neuroinflammatory disorders abstractbackground children neuroinflammatory disorders high rates anxiety depression alongside low rates physical activity given general concerns mental physical health children covid19 pandemic lockdown sought understand sleep anxiety depression physical activity changed lockdown children neuroinflammatory disorders hypothesized outcomes worsen lockdown differ underlying disorder category agemethods patients attending specialized neuroinflammatory clinic n314 completed questionnaires n821 responses jan 2017aug 2020 assessing sleep anxiety depression physical activity respondents either childhoodonset chronic recurrent neuroinflammatory disorders crni history autoimmune encephalitis ae monophasic acquired demyelinating syndromes monoads performed linear mixed models examine association outcome measures sleep anxiety depression physical activity categories disorder type sex age physical activity relapses time pre vs post covid19 lockdown participant id acted random effect account repeated measuresresults sleep significantly increased first 6 months covid19 lockdown f 1 544 5685 p0001 across whole group anxiety depression change pandemic found differing trends age category anxiety decreased teenagers 13y z396 p0001 preteens depression remained higher teenagers preteens across timepoints f 1 597 630 p0012 physical activity levels change pandemic comparison prepandemic f 1 629 192 p0166 anxiety higher inactive individuals regardless timing f 2 547 374 p0024 conclusion youth neuroinflammatory disorders covid19 pandemic lockdown resulted increased hours nighttime sleep result significant overall changes selfreported anxiety depression prelockdown teenagers higher depression anxiety scores preteens postlockdown anxiety depression scores decreased teenagers compared preteens physical activity low pre postlockdown rates anxiety higher inactive participants timepoints differences based age suggest younger children 13 years negatively affected pandemic older children 13 years,1.0
serum saliva myelin basic protein multiple sclerosis biomarker basic clin neurosci 2021 mayjun 12 3 309314 doi 1032598 bcn20219502 epub 2021 may 1abstractintroduction multiple sclerosis ms presented motor sensory function loss caused demyelination following axonal lesion myelin basic protein mbp one key elements myelin cover examined level mbp serum stimulated unstimulated saliva suitable biomarker detecting msmethods casecontrol study performed 29 healthy women 32 definitive relapsingremitting ms patients hospitalized imam reza hospital tehran iran mbp level assayed serum stimulated unstimulated whole salivaresults mbp expressed lower level serum stimulated saliva ms patients compared control group serum mbp level considerable correlation stimulated saliva level receiver operating characteristic analysis showed significant diagnostic ability mbp discriminate ms patients serum stimulated saliva controlsconclusion serum saliva level mbp lower ms may considered potential biomarker mspmid34917290 pmcpmc8666920 doi1032598 bcn20219502,1.0
human endogenous retroviruses herv nonherv viruses incorporated human genome role development autoimmune diseases j transl autoimmun 2021 dec 9 4100137 doi 101016 jjtauto2021100137 ecollection 2021abstractgenomic incorporation viruses human endogenous retroviruses hervs components genome possibly originated incorporating ancestral exogenous viruses roles evolution human genome gene expression pathogenesis autoimmune diseases ads neoplastic phenomena subject intense research review analyzes evolutionary virological aspects hervs viruses incorporate genome human genome known role genesis ads insights helpful understand possible role autoimmunity genesis hervs ancestral viruses hervs modern viruses ability incorporate human genome interact hervspmid34917914 pmcpmc8669383 doi101016 jjtauto2021100137,0.0
urine specific gravity identify predict hydration need als amyotroph lateral scler frontotemporal degener 2021 dec 1718 doi 101080 2167842120212013894 online ahead printabstractintroduction multiple factors contribute increased risk dehydration amyotrophic lateral sclerosis als contributes shortened survival independent nutritional status assessment hydration doubly labeled water restricted due limited availability gold standard technique clinical use prompted us examine utility urinespecific gravity usg predictor hydration need als subjects material methods using data multicenter study 80 als subjects 250 visits conducted secondary analysis original data set doubly labeled water experiments used crosssection data one visit per 75 subjects model selection step test set repeated measures analysis validation step data 63 subjects 142 followup visits sensitivity detect inadequate water turnover rate surrogate water intake goal predictive model presented clinical use results discussion final predictive model estimate water requirement included usg gender body mass index alsfrs gross motor subscale score developed bestfit equation estimate water intake usg determine hydration status improve clinical care realworld als subjectspmid34918583 doi101080 2167842120212013894,0.0
leiomyomatosislike lymphangioleiomyomatosis case report colonic manifestation tuberous sclerosis medicine baltimore 2021 dec 17 100 50 e27723 doi 101097 md0000000000027723abstractintroduction tuberous sclerosis complex inherited multisystemic disorder manifestations various organ systems result mutation 1 2 tumor suppressor genes tuberous sclerosis complex1 tuberous sclerosis complex2 perivascular epithelioid cell tumors shown associated gene mutations include variety tumors angiomyolipomas lymphangioleiomyomatosispatient concerns report present case 28yearold woman presenting symptoms severe abdominal pain nausea medical history cardiac rhabdomyoma adenoma sebaceum ash leaf spots bilateral renal angiomyolipomas retinal hamartoma manifestations tuberous sclerosis complex patient operated twice colonic perforations rectosigmoid ileocecal regions pathologic examination revealed multiple tumoral lesions specimensdiagnosis tumor consisted myomatous component nodules composed spindle cells fascicular array lymphangiomatous component epithelioid cells observed immunohistochemically smooth muscle markers desmin sma positive epithelioid component showed hmb45 positivity diagnosis leiomyomatosislike lymphangioleiomyomatosis established due morphological immunohistochemical features presence tumor multiple foci widespread lymphovascular invasioninterventions patient perforation bowel twice hospital stay underwent hartmann operation ileocecal resection 2 different surgical operationsoutcomes second operation patient developed fever diagnosed sarscov2 infection complication observed stay patients followup unremarkableconclusion perivascular epithelioid cell tumors associated tuberous sclerosis can rarely appear colon therefore lymphangioleiomyomatosis differential diagnosis tuberous sclerosis patient presenting colonic tumorpmid34918628 doi101097 md0000000000027723,0.0
genetic immunological contributors virusinduced paralysis brain behav immun health 2021 nov 26 18100395 doi 101016 jbbih2021100395 ecollection 2021 decabstractinfection single virus can evoke diverse immune responses resulting different neurological outcomes depending hosts genetic background study heterogenous viral response use theilers murine encephalomyelitis virus tmev model virally induced neurological phenotypes immune responses collaborative cross cc mice cc resource consists genetically distinct reproducible mouse lines thus providing population model genetic heterogeneity similar humans examined different cc strains effect chronic stage tmevinduced immune responses neurological outcomes throughout 90 days post infection dpi particular focus limb paralysis measuring serum levels 23 different cytokines chemokines cc strain demonstrated unique set immune responses regardless presence absence tmev rna using stepwise regression significant associations identified il1 rantes paralysis frequency scores better understand interactions evaluated multiple aspects different cc genetic backgrounds including haplotypes genomic regions previously linked tmev pathogenesis viral clearance persistence individual cytokine levels tmevrelevant gene expression results demonstrate loci previously associated tmev outcomes provide incomplete information regarding tmevinduced paralysis cc strains overall findings provide insight complex roles immune response pathogenesis virusassociated neurological diseases influenced host genetic backgroundpmid34917987 pmcpmc8645428 doi101016 jbbih2021100395,0.0
feasibility cognitive rehabilitation patients advanced multiple sclerosis pilot study mult scler j exp transl clin 2021 dec 10 7 4 20552173211064473 doi 101177 20552173211064473 ecollection 2021 octabstractbackground feasibility cognitive rehabilitation rarely investigated patients advanced multiple sclerosismethods eighteen patients advanced multiple sclerosis median edss 75 randomized restorative compensatory cognitive rehabilitation feasibility determined adherence rate completion rate patient satisfaction selfreported fatigue training difficulty training durationresults adherence rates completion rates 70 patients highly satisfied groups energy levels decreased minimally sessions pre 69 vs post 64 training difficulty 46 duration 57 close ideal scale 110 5 ideal conclusions cognitive rehabilitation minor adjustments appears feasible patients advanced multiple sclerosispmid34917392 pmcpmc8669124 doi101177 20552173211064473,0.0
psychometric properties hads measure anxiety depression among multiple sclerosis patients croatia front psychol 2021 nov 30 12794353 doi 103389 fpsyg2021794353 ecollection 2021abstractdepression anxiety common complaints patients multiple sclerosis ms study objective investigate factor structure internal consistency correlates croatian version hospital anxiety depression scale hads patients ms total 179 patients ms 999 controls included online survey subjects completed hads selfadministered questionnaires capturing information demographic education level diseaserelated variables multiple sclerosis impact scale29 msis29 psychometric properties examined estimating validity reliability factor structure hads patients ms two hads subscales anxiety depression excellent internal consistencies cronbachs value 082083 factor analysis confirmed twofactor structure convergent validity hads subscales appeared good due significant correlations hads msis29 receiver operating characteristic roc analysis indicates hads subscales significant diagnostic validity group differentiation hierarchical regression analysis using msis29 subscales criterion variables showed consistent evidence incremental validity hads hads reliable valid selfassessment scale patients ms suggested used clinical monitoring psychiatric psychological status patients mspmid34917005 pmcpmc8670005 doi103389 fpsyg2021794353,0.0
neuronal endothelial transglutaminase2 expression experimental autoimmune encephalomyelitis multiple sclerosis neural regen res 2022 jul 17 7 14711472 doi 104103 16735374330598no abstractpmid34916421 doi104103 16735374330598,0.0
comparison 11cpittsburgh compoundb 18fflutemetamol white matter binding pet j nucl med 2021 dec 16jnumed121263281 doi 102967 jnumed121263281 online ahead printabstractpet imaging amyloid ligands emerging molecular imaging technique targeting white matter integrity demyelination amyloid pet ligands 11cpittsburgh compoundb 11cpib considered quantitative measurement myelin content changes multiple sclerosis ms 11cpib commercially available given short halflife 18fpet ligand flutemetamol longer halflife may alternative ability differentiate white matter hyperintensities wmh normal appearing white matter nawm relationship age remains investigated methods cognitively unimpaired cu older younger adults n 61 recruited community responding study advertisement amyloid pet participants prospectively underwent mri 11cpib 18fflutemetamol pet scans mriflair images segmented wmh nawm registered t1weighted mri 11cpib 18fflutemetamol pet images also registered t1weighted image mri 11cpib 18fflutemetamol standard uptake value ratios suvrs wmh nawm calculated using cerebellar crus uptake reference 11cpib 18fflutemetamol results median age 38 years range 3048 younger adults 67 years range 6183 older adults wmh nawm suvrs higher 18fflutemetamol 11cpib older p0001 younger p0001 cu adults 11cpib 18fflutemetamol suvrs higher older compared younger cu adults wmh p0001 nawm p0001 11cpib 18fflutemetamol suvrs higher nawm compared wmh older p0001 younger p0001 cu adults apparent difference 11cpib versus 18fflutemetamol suvrs differentiating wmh nawm older younger adults conclusion 11cpib 18fflutemetamol show similar topographical pattern uptake white matter similar association age wmh nawm 11cpib 18fflutemetamol can also effectively distinguish wmh nawm however given longer halflife commercial availability higher binding potential 18fflutemetamol can alternative 11cpib molecular imaging studies specifically targeting ms evaluate white matter integritypmid34916245 doi102967 jnumed121263281,1.0
phosphoinositide3kinase regulatory subunit 4 participates occurrence development amyotrophic lateral sclerosis regulating autophagy neural regen res 2022 jul 17 7 16091616 doi 104103 16735374330621abstractthe development amyotrophic lateral sclerosis als may related abnormal alterations multiple proteins previous study revealed expression phosphoinositide3kinase regulatory subunit 4 pik3r4 decreased als however role pik3r4 als pathogenesis remains unknown study first find transfection pc12 cells small interfering rna pik3r4 gene significantly decreased expression levels pik3r4 autophagyrelated proteins p62 lc3 additionally vivo experiments revealed pik3r4 protein extensively expressed anterior horn posterior horn central canal areas surrounding central canal cervical thoracic lumbar segments spinal cord adult mice pik3r4 protein mainly expressed neurons within spinal lumbar segments pik3r4 p62 expression levels significantly decreased preonset onset stages als disease tg sod1g93a 1gur mice compared control mice proteins markedly increased progression stage lc3 protein expression change progression als findings suggest pik3r4 likely participates prevention als progression study approved ethics committee animal care use jiangxi provincial peoples hospital affiliated peoples hospital nanchang university approval 2020025 march 26 2020pmid34916448 doi104103 16735374330621,0.0
embedding electronic health records onto knowledge network recognizes prodromal features multiple sclerosis predicts diagnosis j med inform assoc 2021 dec 16ocab270 doi 101093 jamia ocab270 online ahead printabstractobjective early identification chronic diseases pillar precision medicine can lead improved outcomes reduction disease burden lower healthcare costs predictions patients health trajectory improved application machine learning approaches electronic health records ehrs however methods traditionally relied black box algorithms can process large amounts data unable incorporate domain knowledge thus limiting predictive explanatory power present method incorporating domain knowledge clinical classifications embedding individual patient data biomedical knowledge graphmaterials methods modified version page rank algorithm implemented embed millions deidentified ehrs biomedical knowledge graph spoke resulted highdimensional knowledgeguided patient health signatures ie spokesigs subsequently used features random forest environment classify patients risk developing chronic diseaseresults model predicted disease status 5752 subjects 3 years diagnosed multiple sclerosis ms auc 083 spokesigs outperformed predictions using ehrs alone biological drivers classifiers provided insight underpinnings prodromal msconclusion using data ehr input spokesigs describe patients clinical biological levels provide clinical use case detecting ms 5 years prior documented diagnosis clinic illustrate biological features distinguish prodromal ms statepmid34915552 doi101093 jamia ocab270,0.0
dimethyl fumarate attenuates lps induced septic acute kidney injury suppression nfb p65 phosphorylation macrophage activation int immunopharmacol 2021 dec 13 102108395 doi 101016 jintimp2021108395 online ahead printabstractseptic acute kidney injury aki always accounts high mortality septic patients icu due well understood mechanism infection immuneregulation kidney dysfunction lack effective therapy without side effects dimethyl fumarate dmf immunomodulatory molecule approved treatment multiple sclerosis however therapeutic effect immunomodulatory role underlying dmf action septic aki unclear study aimed elucidate role dmf lipopolysaccharide lps induced septic aki involving macrophage regulation current study administered dmf oral gavage mice lpsinduced aki harvested serum kidney three different time points isolated bone marrowderived macrophages bmdms mice stimulated lps followed dmf treatment explore immunomodulatory role dmf macrophages depleted macrophages mice using liposomal clodronate dmf treatment upon lpsinduced septic aki observed dmf attenuated renal dysfunction murine pathological kidney injury lps injection dmf inhibit translocation phosphorylated nfb p65 suppress macrophage activation lpsinduced aki dmf reduced secretion tnf il6 whereas increased secretion il10 arg1 bmdms lps stimulation dmf also inhibited nfb p65 phosphorylation bmdms lps stimulation importantly effect dmf lpsinduced aki macrophage activation translocation phosphorylated nfb p65 impaired upon macrophage depletion thus dmf attenuate lpsinduced septic aki suppression nfb p65 phosphorylation macrophage activation work suggested potential therapeutic role dmf patients icu threatened septic akipmid34915410 doi101016 jintimp2021108395,0.0
rna binding protein imp2 drives stromalth17 cell circuit autoimmune neuroinflammation jci insight 2021 dec 16e152766 doi 101172 jciinsight152766 online ahead printabstractstromal cells emerging key drivers autoimmunity part producing inflammatory chemokines orchestrate inflammation chemokine expression regulated transcriptionally also posttranscriptional mechanisms specific drivers still incompletely defined ccl2 mcp1 multifunctional chemokine drives myeloid cell recruitment experimental autoimmune encephalomyelitis eae il17driven model multiple sclerosis ccl2 produced lymph node ln stromal cells essential immunopathology show ccl2 mrna upregulation human stromal fibroblasts response il17 requires rna binding protein rbp insulin like growth factor 2 mrna binding protein 2 igf2bp2 imp2 expressed almost exclusively nonhematopoietic cells imp2 binds directly ccl2 mrna markedly extending transcript halflife thus required efficient ccl2 secretion consistent imp2 mice showed reduced ccl2 production ln eae causing impairments monocyte recruitment th17 cell polarization imp2 mice fully protected cns inflammation moreover deletion imp2 eae onset sufficient mitigate disease severity data show posttranscriptional control ccl2 stromal cells imp2 required permit il17driven progression eae pathogenesispmid34914635 doi101172 jciinsight152766,0.0
abstracts virtual symposium signal transduction bloodbrain barriers n,0.0
nuclear receptor nur77 role chronic inflammatory diseases essays biochem 2021 jul 30ebc20210004 doi 101042 ebc20210004 online ahead printabstractnur77 nuclear receptor implicated regulator inflammatory disease expression nur77 increases upon stimulation immune cells differentially expressed chronically inflamed organs human experimental models furthermore variety animal models dedicated study inflammatory diseases changes nur77 expression alter disease outcome available studies comprise wealth information function nur77 diverse cell types tissues negative crosstalk nur77 nfb signaling complex example nur77 effector function alternative mechanism action established involving nur77mediated modulation metabolism macrophages well t cells review summarize current knowledge role nur77 atherosclerosis inflammatory bowel disease multiple sclerosis rheumatoid arthritis sepsis detailed insight control inflammatory responses will essential order advance nur77targeted therapeutic interventions inflammatory diseasepmid34328179 doi101042 ebc20210004,0.0
gene prediction agingrelated diseases based dnn mashup background present bioinformatics research relationship agingrelated diseases genes mainly establishment machine learning multilabel model classify gene existing methods predicting pathogenic genes mainly rely specific types gene features directly encode multiple features different dimensions use encoder concatenate predict final results will subject many limitations applicability algorithm possible shortcomings include incomplete coverage gene features single type biomics data overfitting small dimensional datasets single encoder underfitting larger dimensional datasetsmethodswe use known gene disease association data gene descriptors gene ontology terms go protein interaction data ppi pathdip kyoto encyclopedia genes genomes genes kegg etc input deep learning predict association genes diseases innovation use mashup algorithm reduce dimensionality ppi go large biological networks add new pathway data kegg database combine variety biological information sources modular deep neural network dnn predict genes related aging diseasesresult conclusionthe results show algorithm effective standard neural network algorithm area roc curve 08795 09153 gradient enhanced tree classifier logistic regression classifier paper firstly use dnn learn similar genes associated known diseases complex multidimensional feature space provide evidence assumed genes associated certain disease,0.0
dopaminergic stimulation leads bcell infiltration central nervous system upon autoimmunity background recent evidence shown dopamine major regulator inflammation accordingly dopaminergic regulation immune cells plays important role physiopathology inflammatory disorders multiple sclerosis ms inflammatory disease involving cd4+ tcelldriven autoimmune response central nervous system cns derived antigens evidence animal models suggested b cells play fundamental role antigenpresenting cells apc restimulating cd4+ t cells cns well regulating tcell response mean inflammatory antiinflammatory cytokines addressed role dopamine receptor d3 drd3 displays highest affinity dopamine b cells animal models msmethodsmice harbouring drd3deficient drd3sufficient b cells generated bone marrow transplantation recipient mice devoid b cells mice compared development experimental autoimmune encephalomyelitis eae induced immunization myelin oligodendrocyte glycoprotein mog derived peptide pmog model leads cnsautoimmunity irrespective apcfunction b cells immunization fulllength human mog protein humog model antigenspecific activated b cells display fundamental apcfunction cns apcfunction assessed vitro pulsing b cells humogcoated beads coculturing mogspecific t cellsresultsour data show selective drd3 deficiency b cells abolishes disease development humoginduced eae model mechanistic analysis indicates although drd3signalling affect apcfunction b cells drd3 favours cnstropism subset proinflammatory b cells humoginduced eae model effect associated higher cxcr3 expression conversely results show selective drd3 deficiency b cells exacerbates disease severity pmoginduced eae model analysis shows drd3stimulation increased expression cnshoming molecule cd49d bcell subset antiinflammatory features thus attenuating eae manifestation pmoginduced eae modelconclusionsour findings demonstrate drd3 b cells exerts dual role cnsautoimmunity favouring cnstropism proinflammatory b cells apcfunction promoting cnshoming b cells antiinflammatory features thus results show drd3signalling b cells critical regulator cnsautoimmunity,1.0
autophagy deficiency neurodevelopmental disorders abstractautophagy cell selfdigestion pathway lysosome plays critical role maintaining cellular homeostasis cytoprotection characterization autophagy related genes cell animal models reveals diverse physiological functions autophagy various cell types tissues central nervous system recycling injured organelles misfolded protein complexes aggregates autophagy integrated synaptic functions neurons subjected distinct regulation presynaptic postsynaptic neuronal compartments plethora studies shown neuroprotective function autophagy major neurodegenerative diseases alzheimers disease ad parkinsons disease pd huntingtons disease hd amyotrophic lateral sclerosis als recent human genetic genomic evidence demonstrated emerging significant role autophagy human brain development prevention spectrum neurodevelopmental disorders will review evidence demonstrating causal link autophagy deficiency congenital brain diseases mechanism whereby autophagy functions neurodevelopment therapeutic potential autophagy,1.0
lpa1 signaling drives schwann cell dedifferentiation experimental autoimmune neuritis background lysophosphatidic acid lpa pleiotropic lipid messenger addresses least six specific gprotein coupled receptors accumulating evidence indicates significant involvement lpa immune cell regulation well schwann cell physiology potential relevance pathophysiology peripheral neuroinflammation however role lpa signaling inflammatory neuropathies remained completely undefined given broad expression lpa receptors schwann cells cells innate adaptive immune system hypothesized inhibition lpa signaling may ameliorate course disease experimental autoimmune neuritis ean methodswe induced active ean inoculation myelin protein 2 peptide p25578 female lewis rats animals received orally available lpa receptor antagonist am095 specifically targeting lpa1 receptor subtype am095 administered daily via oral gavage therapeutic regimen 10 28 days postimmunization dpi analyses based clinical testing hemogram profiles immunohistochemistry morphometric assessment myelinationresultslewis rats treated am095 displayed significant improvement clinical scores notably remission phase cellular infiltration sciatic nerve discretely affected am095 hemogram profiles indicated impact circulating leukocytes however sciatic nerve immunohistochemistry revealed reduction number schwann cells expressing dedifferentiation marker sox2 paralleled corresponding increase differentiating sox10positive schwann cells line morphometric analysis sciatic nerve semithin sections identified significant increase largecaliber myelinated axons 28 dpi myelin thickness unaffected am095conclusionthus lpa1 signaling may present novel therapeutic target treatment inflammatory neuropathies potentially affecting regenerative responses peripheral nerve modulating schwann cell differentiation,1.0
dmts trialed individuals ppms spms without recent disease activity discasemodifying therapy dmt ms one important elements treatment plan across spectrum patients ms may ben efit window opportunity often clearest carly relapsing forms ms appropriate use dmt can effectively prevent relapses disability potentially delay onset secondary progressive ms advances ms thera peutics resulted highly effective dmts generally safe well tolerated patients ever derive benefit compared eras choosing higher efficacy therapy meant taking much risk despite advances appli cation dmt progressive ms populations less clear controversial given evidence clinical trials patients benefit fact risk associated dmt may higher patients population progressive forms ms personalized approach care possible justified select patients appropriate therapy maximize benefit reduce risk complications optimize value healthcare system multiple reasons personalized approach universal treatment approach appropriate pro gressive msfirst evidence laboratory suggests heterogencous mechanisms underlie com plex ms disease process specifically mechanisms underlie progression different mechanisms underlie relapses new lesion formation whercas acute inflammation adaptive immune mechanisms dominate relapsing forms disease may coexist progressive ms patients early disease likely pure progression associated mechanisms immune mediated rationale therefore using immunomodu latory therapies approved regulators largely based effect trials relapses new magnetic resonance imaging mri lesions purely progres sive disease well substantiated given complexity mechanisms contribute disability accumulation monolithic definition progressive ms based classic ms phenotype categories may therefore overly simplistic likely heterogencity patient patient mechanisms contributing thus determin ing across board eligibility therapy based phenotype alone may underestimating com plexity consensus phenotypes adapted include discase activity reflection prin ciples absent true biomarkers quantify mechanisms factors age disease duration recency new mri lesion formation recency relapses candidate factors characterize components discase process likely play individual patientssecond evidence clinical trial subanalyses suggests benefit dmt progressive ms,0.0
dmts trialed individuals ppms spms without recent disease activity commentary available,0.0
benefits aquatic exercise adults without chronic disease systematic review metaanalysis scand j med sci sports 2021 dec 16 doi 101111 sms14112 online ahead printabstractaquatic exercise increasingly recommended healthy individuals well people special health conditions systematic review metaanalysis performed synthesize analyse data effects waterbased training wt programs health status physical fitness healthy adults adults diseases develop useful recommendations health sports professionals searched three databases pubmed web science scopus june 2021 randomized trials examined wt adults total 62 studies included 26 involved healthy individuals 36 focused adults chronic diseases healthy group effects wt strength balance cardiorespiratory fitness beneficial indicating usefulness performing wt least 12 weeks 23x week 4665 min session among adults diseases improvements observed patients fibromyalgia balance cardiorespiratory fitness bone diseases pain balance flexibility strength coronary artery disease strength anthropometry hypertension quality life stroke quality life diabetes balance quality life multiple sclerosis quality life balance parkinsons disease pain gait cardiorespiratory fitness quality life research required determine effects wt patients heart disease especially coronary artery disease adults chronic disease benefits physical fitness healthrelated measures mainly observed 816 weeks training wt effective physical activity intention enhance health physical fitness healthy adults adults chronic diseasespmid34913530 doi101111 sms14112,0.0
synaptic loss multiple sclerosis systematic review human postmortem studies front neurol 2021 nov 29 12782599 doi 103389 fneur2021782599 ecollection 2021abstractbackground gray matter pathology plays central role progression multiple sclerosis ms occurrence synaptic loss appears important date still poorly investigated aspect ms pathology systematic review drew recent knowledge synaptic loss human postmortem studies methods conducted systematic search pubmed identify relevant publications publications available from15 june 2021 taken account selected human postmortem studies quantitatively assessed synapse number ms tissue results identified 14 relevant publications 9 reported synaptic loss least one investigated subregion commonly used synaptic marker synaptophysin nonetheless found substantial differences methodology selection reference tissue investigated regions included cortex hippocampus cerebellum thalamus spinal cord conclusion synaptic loss seems take place throughout entire central nervous system however results inconsistent probably due differences methodology moreover synaptic loss appears dynamic process thus nature pathology might captured using vivo synaptic density measurementspmid34912290 pmcpmc8666414 doi103389 fneur2021782599,0.0
erratum objective biomarkers clinical relapse multiple sclerosis metabolomics approach brain commun 2021 dec 8 3 4 fcab283 doi 101093 braincomms fcab283 ecollection 2021abstract corrects article doi 101093 braincomms fcab240 pmid34913033 pmcpmc8667265 doi101093 braincomms fcab283,0.0
antihuman herpesvirus 6 a#x2f b antibodies titers correlate multiple sclerosisassociated retrovirus envelope expression front immunol 2021 nov 29 12798003 doi 103389 fimmu2021798003 ecollection 2021abstracthuman endogenous retrovirus w family envelope proteins phervw env syncytin1 repeatedly associated multiple sclerosis ms focused study phervw env syncytin1 expression levels ms patients relapsing progressive forms healthy donors hd exploring possible relationship epsteinbarr virus ebv human herpesvirus6a b hhv6a b included blood samples 101 ms patients 37 hd analyze antiviral antibody titers elisa phervw env syncytin1 expression levels flow cytometry well qpcr patients relapsing ms forms showed significantly higher phervw env syncytin1 protein gene expression levels hd progressive ms patients also showed significantly higher protein gene expression levels hd relapsing ms patients regarding antiviral antibodies titers antihhv6a b igm levels positively correlated phervw env syncytin1 protein expression levels patients relapsing ms progressive forms patients correlation found antihhva b igg levels therefore phervw env involved ms pathogenesis playing role relapsing progressive forms besides antihhv6a b antibodies positively correlated phervw env expression studies needed better understand possible relationshippmid34912348 pmcpmc8666430 doi103389 fimmu2021798003,0.0
correction psychological wellbeing people multiple sclerosis descriptive review effects obtained mindfulness interventions neurol sci 2021 dec 16 doi 101007 s1007202105812z online ahead printno abstractpmid34913096 doi101007 s1007202105812z,0.0
timeg integrative statistical method partially missing multiomics data sci rep 2021 dec 15 11 1 24077 doi 101038 s4159802103034zabstractmultiomics data integration widely used understand genetic architecture disease multiomics association analysis data collected multiple omics set individuals immensely important biomarker identification sample size data limited presence partially missing individuallevel observations poses major challenge data integration often genotype data available individuals study gene expression methylation information missing different subsets individuals develop statistical model timeg identification diseaseassociated biomarkers casecontrol paradigm integrating abovementioned data types especially presence missing omics data based likelihood approach timeg exploits interrelationship among multiple omics data capture weaker signals remain unidentified singleomic analysis common imputationbased methods application real tuberous sclerosis dataset identified functionally relevant genes disease pathwaypmid34911979 doi101038 s4159802103034z,0.0
perspective insights repurposing pleiotropic efficacy statins neurodegenerative disorders expository appraisal curr res pharmacol drug discov 2020 dec 31 2100012 doi 101016 jcrphar2020100012 ecollection 2021abstractneurodegenerative disorders affects larger population pose great clinical challenge disorders impact quality life individual damaging neurons unit cells brain clinicians faced grave challenge inhibiting progression diseases available treatment options fail meet clinical demand thus treating disease disorder symptomatically hobsons choice goal researchers introduce newer therapies segment introducing new molecule will take long years development hence drug repurposing repositioning can better substitute comparison time consuming expensive drug discovery development cycle presently paradigm shift towards repurposing drugs can witnessed statins previously approved antihyperlipidemic agents limelight research repurposed drugs owing antiinflammatory antioxidant nature statins act neuroprotective several brain disorders attenuate amyloid plaques protein aggregation triggering factors alzheimers parkinsons respectively case huntington disease multiple sclerosis help improving psychomotor symptoms stimulate remyelination thus acting neuroprotective article reviews potential statins treating neurodegenerative disorders along brief discussion safety concerns associated use statins human clinical trial data linked retasking statins neurodegenerative disorders along regulatory perspectives involved drug repositioningpmid34909647 pmcpmc8663947 doi101016 jcrphar2020100012,1.0
gauging role impact drug interactions repurposing neurodegenerative disorders curr res pharmacol drug discov 2021 apr 8 2100022 doi 101016 jcrphar2021100022 ecollection 2021abstractneurodegenerative diseases nd vast origin characterized gradual progressive loss neurons brain region nd can classified according clinical symptoms present eg cognitive decline hyperkinetic hypokinetic movements disorder pathological protein deposited eg amyloid tau alphasynuclein tdp43 alzheimers disease preceded parkinsons prevalent form nd worldwide multiple factors like aging genetic mutations environmental factors gut microbiota bloodbrain barrier microvascular complication etc may increase predisposition towards nd genetic mutation major contributor increasing susceptibility towards nd concept one diseaseone gene obsolete now multiple genes considered involved causing one particular disease also involvement multiple pathological mechanisms like oxidative stress neuroinflammation mitochondrial dysfunction etc contributes complexity makes difficult treated traditional monotargeted ligands aspect polypharmacological drug approach targets multiple pathological pathways time provides best way treat complex networked cns diseases review provided overview nd pathological origin along brief description various genes associated multiple diseases like alzheimers parkinsons multiple sclerosis ms amyotrophic lateral sclerosis als huntingtons comprehensive detail polypharmacology approach mtdls fixeddose combinations along merits traditional singletargeted drug provided review also provides insights current repurposing strategies along regulatory considerationspmid34909657 pmcpmc8663985 doi101016 jcrphar2021100022,0.0
editorial comment paramagnetic rim lesionsan imaging biomarker chronic active lesions multiple sclerosis may help advance research progressive disease ajr j roentgenol 2021 dec 15 doi 102214 ajr2127198 online ahead printno abstractpmid34910543 doi102214 ajr2127198,0.0
order controls disordered droplets structurefunction relationships c9orf72derived poly pr j physiol cell physiol 2021 dec 15 doi 101152 ajpcell003722021 online ahead printabstractamyotrophic lateral sclerosis als frontotemporal dementia ftd thought two distinct neurodegenerative diseases however recent genetic screening careful investigations found genetic pathological overlap among disorders hexanucleotide expansions intron 1 c9orf72 leading cause familial als familial ftd expansions facilitate repeatassociated nonatg initiated translation ran translation producing five dipeptide repeat proteins drps including argrich poly pr proarg poly gr glyarg peptides arg positively charged highly polar amino acid facilitates interactions anionic molecules nucleic acids acidic amino acids via electrostatic forces aromatic amino acids via cationpi interaction suggesting argrich drps underlie pathophysiology als via argmediated molecular interactions argrich drps also reported induce neurodegeneration cellular animal models via multiple mechanisms however remains unclear argrich drps exhibit diverse toxic properties argrich peptides toxic minireview discuss current understanding pathophysiology argrich c9orf72 drps introduce recent findings role arg distribution determinant toxicity contribution pathogenesis alspmid34910602 doi101152 ajpcell003722021,0.0
oligodendrocytes bk channels remyelination f1000res 2021 aug 9 10781 doi 1012688 f1000research534221 ecollection 2021abstractoligodendrocytes wrap multiple lamellae membrane myelin around axons central nervous system cns improve impulse conduction myelin synthesis specialised dynamic responsive local neuronal excitation subtle pathological insults sufficient cause significant neuronal metabolic impairment myelin preservation necessary safeguard neural networks multiple sclerosis ms prevalent demyelinating disease cns ms inflammatory attacks myelin proposed autoimmune cause myelin decay oligodendrocyte loss leaving neurons vulnerable current therapies target prominent neuroinflammation mostly ineffective protecting neurodegeneration progressive neurological disability people ms substantially higher levels extracellular glutamate main excitatory neurotransmitter impairs cellular homeostasis cause excitotoxic stress large conductance ca2 +activated k + channels bk channels preserve myelin allow recovery protecting cells resulting excessive excitability review evaluates role excitotoxic stress myelination bk channels ms pathology explores hypothesis bk channel activation therapeutic strategy protect oligodendrocytes excitotoxic stress ms reduce progression neurological disability used parallel immunomodulatory therapiespmid34909188 pmcpmc8596180 doi1012688 f1000research534221,1.0
siponimod inhibits formation meningeal ectopic lymphoid tissue experimental autoimmune encephalomyelitis neurol neuroimmunol neuroinflamm 2021 dec 15 9 1 e1117 doi 101212 nxi0000000000001117 print 2022 janabstractbackground objectives investigate whether formation retention meningeal ectopic lymphoid tissue melt can inhibited sphingosine 1phosphate receptor 1 5 modulator siponimod baf312 murine model multiple sclerosis ms methods murine spontaneous chronic experimental autoimmune encephalomyelitis eae model featuring meningeal inflammatory infiltrates resembling ms used prevent treat eae siponimod administered daily starting either eae onset peak disease extent cellular composition melt spinal cord parenchyma spleen assessed histology immunohistochemistryresults siponimod applied disease onset ameliorated eae effect also present although less prominent treatment started peak disease treatment siponimod resulted strong reduction extent melt treatment paradigms b t cells diminished meningeal compartmentdiscussion beneficial effects disease course correlated reduction melt suggesting inhibition melt may additional mechanism action siponimod treatment eae studies needed establish causality confirm observation mspmid34911793 doi101212 nxi0000000000001117,0.0
specific hypomethylation programs underpin b cell activation early multiple sclerosis proc natl acad sci u s 2021 dec 21 118 51 e2111920118 doi 101073 pnas2111920118abstractepigenetic changes consistently detected different cell types multiple sclerosis ms however contribution ms pathogenesis remains poorly understood partly sample heterogeneity limited coverage arraybased methods fill gap conducted comprehensive analysis genomewide dna methylation patterns four peripheral immune cell populations isolated 29 ms patients clinical disease onset 24 healthy controls show b cells newonset untreated ms cases display significant methylation changes diseaseimplicated immune cell types consisting global dna hypomethylation signature importantly 4 933 msassociated differentially methylated regions b cells identified epigenetic signature underlies specific genetic programs involved b cell differentiation activation integration methylome changes gene expression susceptibilityassociated regions indicates hypomethylated regions significantly associated upregulation cell activation transcriptional programs altogether findings implicate aberrant b cell function ms etiologypmid34911760 doi101073 pnas2111920118,0.0
challenges persons multiple sclerosis ocrelizumab treatment covid19 pandemic neurol clin neurosci 2021 oct 28 doi 101111 ncn312561 online ahead printabstractbackground coronavirus disease 2019 pandemic caused much fear among people chronic diseases immunosuppressant treatment spreading knowledge infection fatal course populations people multiple sclerosis ocrelizumab treatment share fear aimed investigate treatment lifestyle changes people multiple sclerosis ocrelizumab treatment lockdownmethods surveyed 199 registered multiple sclerosis patients ocrelizumab treatment phoneresults survey delays treating 22 11 patients caused fear immunosuppressive drug use rather general fear contracting fatal disease case traveling hospital visits positive correlation living alone treatment delay p 029 emphasizing role family support just presence another person pandemicconclusion vaccines might soon solve pandemics issue case multiple sclerosis progression think twice discontinuing treatmentpmid34909197 pmcpmc8661795 doi101111 ncn312561,0.0
potential roles nrf2#x2f keap1 signaling anticancer drug interactions curr res pharmacol drug discov 2021 may 4 2100028 doi 101016 jcrphar2021100028 ecollection 2021abstractnuclear factor erythroidderived 2 related factor 2 nrf2 together suppressive binding partner kelchlike echassociated protein 1 keap1 regulates cellular antioxidant response drug metabolism roles nrf2 keap1 signaling pathology many diseases extensively investigated small molecules targeting nrf2 keap1 signaling developed prevent treat diseases multiple sclerosis chronic kidney disease cancer notably nrf2 plays dual roles cancer development treatment activation nrf2 keap1 signaling cancer cells reported promote cancer progression result therapy resistance since cancer patients often suffering comorbidities chronic diseases anticancer drugs coadministrated drugs herbs nrf2 keap1 signaling modulators especially activators common drugs herbs dietary ingredients even developed targets therefore drugdrug herbdrug interactions due modulation nrf2 keap1 signaling considered cancer therapies briefly summarize basic biochemistry physiology functions nrf2 keap1 signaling nrf2 keap1 signaling modulators cancer patients exposed anticancer drugs sensitive nrf2 keap1 signaling aiming call attention potential drugdrug herbdrug interactions anticancer drugs nrf2 keap1 signaling modulatorspmid34909662 pmcpmc8663926 doi101016 jcrphar2021100028,0.0
ponesimod treat multiple sclerosis drugs today barc 2021 dec 57 12 745758 doi 101358 dot202157123353166abstractponesimod act128800 directly bioavailable rapidly reversible sphingosine1phosphate s1p receptor modulator highly selective subtype 1 s1p receptor acts blocking egress lymphocytes lymphoid organs thus limiting entry autoreactive cells central nervous system unlike fingolimod ponesimod require monitoring first dose thanks 14day uptitration regimen markedly reduces incidence cardiodynamic effects related initiation therapy results optimum phase iii trial demonstrated superiority ponesimod teriflunomide disease activity markers without unexpected safety concerns furthermore drug eliminated within 1 week discontinuation allowing reversibility effects ponesimod recently approved us eu treatment relapsing forms multiple sclerosis review summarizes pharmacological characteristics ponesimod main studies led approvalpmid34909803 doi101358 dot202157123353166,0.0
accurate prediction acute pancreatitis severity based genomewide cell free dna methylation profiles background patients severe acute pancreatitis sap high mortality thus early diagnosis interventions critical improving survival however conventional tests limited acute pancreatitis ap stratification aimed assess ap severity integrating informative clinical measurements cell free dna cfdna methylation markersmethodsone hundred seventyfive blood samples collected 61 ap patients multiple time points plus 24 samples healthy individuals genomewide cfdna methylation profiles samples characterized reduced representative bisulfite sequencing clinical blood tests covering 93 biomarkers performed ap patients within 24 h sap predication models built based cfdna methylation conventional blood biomarkers separately combinationresultswe identified 565 59 cfdna methylation markers informative acute pancreatitis severity markers used develop prediction models ap sap area receiver operating characteristic 092 081 respectively twelve blood biomarkers systematically screened predictor sap sensitivity 875 sap specificity 100 mild acute pancreatitis significantly higher existing blood tests expanded model integrating 12 conventional blood biomarkers 59 cfdna methylation markers improved sap prediction sensitivity 922conclusionsthese findings demonstrated accurate prediction sap integration conventional novel blood molecular markers paving way early effective sap intervention noninvasive rapid diagnostic test,0.0
delphimethodbased consensus guideline definition treatmentresistant depression clinical trials mol psychiatry 2021 dec 15 doi 101038 s4138002101381x online ahead printabstractcriteria treatmentresistant depression trd partially responsive depression prd subtypes major depressive disorder mdd unequivocally defined present document used delphimethodbased consensus approach define trd prd serve operational criteria future clinical studies especially conducted regulatory purposes reviewed literature brought together group international experts including clinicians academics researchers employees pharmaceutical companies regulatory bodies representatives one person lived experience evaluate stateoftheart main controversies regarding current classification provided recommendations design clinical trials guide research unmet needs knowledge gaps report will feed one main objectives european patientcentric clinical trial platforms innovative medicines initiative eupearl imi mdd project design protocol platform trials new medications trd prdpmid34907394 doi101038 s4138002101381x,0.0
orexins promising target digestive cancers inflammation obesity metabolism dysfunctions world j gastroenterol 2021 nov 28 27 44 75827596 doi 103748 wjgv27i447582abstracthypothalamic neuropeptides named hypocretin orexins identified 1998 regulate critical functions wakefulness central nervous system past 20 years revealed orexins receptors system also present peripheral nervous system participated regulation multiple functions including blood pressure regulation intestinal motility hormone secretion lipolyze reproduction functions associated peripheral functions found orexins receptors involved various diseases acute chronic inflammation metabolic syndrome cancers present review suggests orexins orexin neural circuitry represent potential therapeutic targets treatment multiple pathologies related inflammation including intestinal bowel disease multiple sclerosis septic shock obesity digestive cancerspmid34908800 pmcpmc8641057 doi103748 wjgv27i447582,0.0
mir122 affects initiation maintenance hepatitis c virus infections j virol 2021 dec 15jvi0190321 doi 101128 jvi0190321 online ahead printabstracta liverspecific microrna mir122 anneals hcv genomic 5 terminus essential virus replication cell culture however bicistronic hcv replicons full length rnas specific mutations 5 utr can replicate albeit low levels without mir122 study identified hcv rnas lacking structural gene region emcv iresregulated translation reduced requirements mir122 addition found smaller proportion cells supported mir122independent replication compared population cells supporting mir122dependent replication viral protein levels per positive cell similar proportion cells supporting mir122independent replication increased amount viral rna delivered suggesting establishment mir122independent replication cell affected amount viral rna delivered hcv rnas replicating independent mir122 affected supplementation mir122 suggesting mir122 essential maintenance mir122independent hcv infection however mir122 supplementation small positive impact mir122dependent replication suggesting minor role enhancing ongoing virus rna accumulation suggest mir122 functions primarily initiate hcv infection minor influence maintenance present model mir122 required replication complex formation beginning infection also supports new replication complex formation ongoing infection infected cell division importance mechanism mir122 promotes hcv life cycle well understood role directly promoting genome amplification still debated study shown mir122 increases rate viral rna accumulation promotes establishment hcv infection greater number cells absence mir122 however also confirm minor role promoting ongoing virus replication propose role initiation new replication complexes throughout virus infection study implications use antimir122 potential hcv therapypmid34908444 doi101128 jvi0190321,0.0
direct imaging white matter ultrashort t2 components 7tesla magn reson imaging 2021 dec 11s0730725x 21 002393 doi 101016 jmri202111016 online ahead printabstractpurpose demonstrate direct imaging white matter ultrashort t2 components 7 tesla using inversion recovery ir enhanced ultrashort echo time ute mri investigate characteristics potentials limitations establish clinical protocolmaterial methods ir ute technique suppresses long t2 signals within white matter using adiabatic inversion combination dualecho difference imaging artifacts arising 7 t long t2 scalp fat components reduced frequency shifting ir pulse frequencies inverted likewise 8 healthy volunteers t2 relaxation times white matter quantified 20 healthy volunteers ute difference fraction contrast evaluated finally 6 patients multiple sclerosis ms performance technique assessedresults frequency shift 12 ppm ir pulse ie towards fat frequency provided good suppression artifacts ultrashort compartment 68 6 t2 time 147 58 s quantified chemical shift 36 05 ppm water within healthy volunteers white matter stable ultrashort t2 fraction contrast calculated ms patients significant fraction reduction identified lesions well normalappearing white matter observedconclusions quantification results indicate observed ultrashort components arise primarily myelin tissue direct ir ute imaging white matter ultrashort t2 components thus feasible 7 t high quantitative intersubject repeatability good detection signal loss mspmid34906631 doi101016 jmri202111016,1.0
largescale genomic study reveals robust activation immune system following advanced inner engineering meditation retreat proc natl acad sci u s 2021 dec 21 118 51 e2110455118 doi 101073 pnas2110455118abstractthe positive impact meditation human wellbeing well documented yet molecular mechanisms incompletely understood applied comprehensive systems biology approach starting wholeblood gene expression profiling combined multilevel bioinformatic analyses characterize coexpression transcriptional proteinprotein interaction networks identify meditationspecific core network advanced 8d inner engineering retreat program found response oxidative stress detoxification cell cycle regulation pathways downregulated meditation strikingly 220 genes directly associated immune response including 68 genes related interferon signaling upregulated significant expression changes inflammatory genes robust meditationspecific immune response network significantly dysregulated multiple sclerosis severe covid19 patients work provides foundation understanding effect meditation suggests meditation behavioral intervention can voluntarily nonpharmacologically improve immune response treating various conditions associated excessive persistent inflammation dampened immune system profilepmid34907015 doi101073 pnas2110455118,0.0
efficacy bcg vaccine animal models neurological disorders vaccine 2021 dec 11s0264410x 21 016133 doi 101016 jvaccine202112005 online ahead printabstractthe bacillus calmetteguerin bcg vaccine can modulate immune response via antigenspecific immune response also can confer nonspecific protection therapeutic benefits several neurological conditions different heterologous effects vaccination however precise mechanism action bcg remains unclear review different mechanisms underlying bcgmediated immunity will explained animal models reflects characteristic feature neuroinflammatory neurodegenerative disorders multiple sclerosis alzheimers parkinsons diseases furthermore evidence beneficial effect bcg neuropsychiatric disorders will also discussedpmid34906393 doi101016 jvaccine202112005,0.0
trpv1 channel mediates nlrp3 inflammasomedependent neuroinflammation microglia cell death dis 2021 dec 14 12 12 1159 doi 101038 s41419021044509abstractmultiple sclerosis ms chronic inflammatory autoimmune disease central nervous system cns nlrp3 inflammasome considered important regulator immunity inflammation play critical role ms however underlying mechanism nlrp3 inflammasome activation fully understood identified trpv1 transient receptor potential vanilloid type 1 channel microglia ca2+ influxregulating channel played important role nlrp3 inflammasome activation deletion pharmacological blockade trpv1 inhibited nlrp3 inflammasome activation microglia vitro research revealed trpv1 channel regulated atpinduced nlrp3 inflammasome activation mediating ca2+ influx phosphorylation phosphatase pp2a microglia addition trpv1 deletion alleviate mice experimental autoimmune encephalomyelitis eae reduce neuroinflammation inhibiting nlrp3 inflammasome activation data suggested trpv1 channel microglia can regulate nlrp3 inflammasome activation consequently mediate neuroinflammation meanwhile study indicated trpv1ca2+pp2a pathway may novel regulator nlrp3 inflammasome activation pointing trpv1 potential target cns inflammatory diseasespmid34907173 doi101038 s41419021044509,0.0
lycium barbarum polysaccharide promotes m2 polarization bv2 microglia induced lps via inhibiting tlr4#x2f nfb signaling pathway xi bao yu fen zi mian yi xue za zhi 2021 dec 37 12 10661072abstractobjective investigate effect lycium barbarum polysaccharide lbp polarization bv2 microglia m1 m2 induced lipopolysaccharide lps mechanism methods bv2 microglia divided control group lps group lbp treatment group 06 09 12 g l mtt assay used observe cell viability bv2 cells griess assay used detect release levels tumor necrosis factor tnf interleukin1 il1 detected elisa expressions tolllike receptor 4 tlr4 nuclear factor kappa b nfb inducible nitric oxide synthase inos arginase1 arg1 detected immunofluorescence cytochemistry western blot used evaluate protein levels ionized calciumbinding adaptor molecule1 iba1 tlr4 nfb inos arg1 results significant difference cell survival rate treatment different doses lbp compared control group lps group bv2 microglia activated amoebalike shape increased release expressions iba1 tlr4 nfb inos tnf il1 il6 significantly increased expressions arg1 il10 significantly decreased lbp group iba1 tlr4 nfb inos tnf il1 il6 dramatically decreased negatively correlated dose arg1 il10 increased positively correlated dose conclusion lbp inhibits activation bv2 microglia induced lps promots m2 polarization may realized inhibiting tlr4 nfb signaling pathwaypmid34906293,0.0
development exercise programme balance abilities people multiple sclerosis development concept study using rasch analysis background people multiple sclerosis pwms frequently impaired balance early stage disease balance difficulties can divided categories although date lack scientific foundation impaired balance pwms can addressed using specific challenging exercises exercises provide optimal challenge point however difficulty balance exercises often unknown making difficult target exercises individuals abilitiesthe aims study develop exercise programme pwms relating exercises balance problem categories establish order difficulty exercises category evaluate content structural validity exercise programmemethodsa construct map approach used design develop exercise programme pwms potentially relevant balance exercises identified framework set comprising four dimensions subsequently reduced three dimensions balance exercises relevance comprehensibility comprehensiveness exercise programme rated 13 physiotherapists also linked 19 key exercises balance categories total 65 pwms performed 19 balance exercises rated difficulty commented relevance comprehensibility exercise rasch model used evaluate relative difficulty exercises assess fit data rasch model rating scale model used unidimensional latent trait model polytomous item responsesresultsevaluation physiotherapists pwms indicated content validity exercise programme adequate rasch analysis showed latent trait balance exercises pwms comprised three subdimensions stable bos sway step walk 19 balance exercises showed adequate fit respective dimensions difficulties balance exercises adequate cover ability spectrum pwmsconclusiona balance exercise programme pwms comprising three dimensions balance exercises developed difficulty estimates established exercises can used targeted balance training content structural validity programme adequate,0.0
initial clinical manifestation multiple sclerosis immunization pfizerbiontech covid19 vaccine j neuroimmunol 2021 oct 20 361577755 doi 101016 jjneuroim2021577755 online ahead printabstractvaccine administration may involved development central nervous system demyelinating diseases covid19 vaccine administered entire population date little association vaccination risk developing multiple sclerosis ms suggested case reports published present 40yearold woman developed cervical myelitis receiving covid19 vaccine myelitis considered initial clinical manifestation ms case suggests possible link vaccination clinical ms attackpmid34700047 doi101016 jjneuroim2021577755,1.0
weight bearing measure disease progression experimental autoimmune encephalomyelitis j neuroimmunol 2021 oct 1 361577730 doi 101016 jjneuroim2021577730 online ahead printabstractmotor disability multiple sclerosis often modeled using experimental autoimmune encephalomyelitis eae assessed using clinical score cs observerdependent tool can lead potential bias advanced dynamic weight bearing adwb system evaluated observerindependent measurement eae symptoms adwb detected weight shifts onto front paws mice develop hindlimb motor disability cs adwb strongly correlated indicated measures comparable suggesting adwb may appropriate observerindependent tool assessment eae progressionpmid34628133 doi101016 jjneuroim2021577730,0.0
immunological effects dimethyl fumarate treatment blood csf patients primary progressive ms j neuroimmunol 2021 oct 22 361577756 doi 101016 jjneuroim2021577756 online ahead printabstractdimethyl fumarate efficient therapy used widely patients relapsingremitting multiple sclerosis rrms however lacking effect treatment recently reported patients primary progressive ms ppms hjsgaard chow et al 2021 order analyze immunological treatment response investigated systemic intrathecal immunological effects dimethyl fumarate dmf treatment 50 patients ppms participated 48week randomized controlled trial dimethyl fumarate vs placebo found substantial systemic immunomodulatory effects dmf treatment comparable observed patients rrms however intrathecal effects limited restricted cd4+ t cells presumably resulting higher concentrations intrathecal il7pmid34739914 doi101016 jjneuroim2021577756,0.0
carbonsilicon switch led discovery novel synthetic cannabinoids therapeutic effects mouse model multiple sclerosis eur j med chem 2021 oct 5 226113878 doi 101016 jejmech2021113878 online ahead printabstractcannabinoids widely studied therapeutic agents treatment various diseases among thc cbd two important phytocannabinoids served structural templates design synthetic analogs study designed synthesized variety novel cannabinoids based structural backbones thc cbd using carbonsilicon switch strategy dimethyl silyl group introduced tail group two series novel compounds designed synthesized showed wide range binding affinity cb1 cb2 receptors among compound 15b identified nonselective cb1 cb2 agonist 38b selective agonist cb2 receptor preliminary screening showed compounds improved metabolic stability carbon analogs good vivo pharmacokinetic profiles furthermore 15b 38b significantly alleviated phenotype experimental autoimmune encephalomyelitis eae micepmid34634742 doi101016 jejmech2021113878,0.0
lateonset shortterm intermittent fasting reverses agerelated changes calcium buffering inhibitory synaptic transmission mouse basal forebrain neurons aging often associated cognitive decline recurrent cellular molecular impairments lifelong caloric restriction cr may delay agerelated cognitive deterioration well onset neurological disease recent studies suggest lateonset shortterm intermittent fasting may show comparable beneficial effects lifelong cr improve brain health used new optogenetic aging model study effects lateonset 18 months shortterm 46 weeks agerelated changes gabaergic synaptic transmission intracellular calcium ca2+ buffering cognitive status utilized male mice bacterial artificial chromosome bac transgenic mouse line stable expression channelrhodopsin2 chr2 variant h134r vgatchr2 h134r eyfp reduced synaptic preparation allows specific optogenetic light stimulation gabaergic synaptic terminals across aging performed quantal analysis using method failures model show shortterm reverses agerelated decrease quantal content gabaergic synapses likewise shortterm also reversed agerelated changes ca2+ buffering spontaneous gabaergic synaptic transmission basal forebrain bf neurons aged mice findings suggest lateonset shortterm can reverse agerelated physiological impairments mouse bf neurons 4 weeks sufficient reverse agerelated cognitive declinesignificant statementhere demonstrate plasticity aging brain reversal welldefined hallmarks brain aging using shortterm intermittent fasting initiated later life therapeutics currently available treat agerelated neurological dysfunction although synaptic dysfunction occurs aging neurological disease topic intense research using new reduced synaptic preparation optogenetic stimulation able study agerelated synaptic mechanisms greater detail several neurophysiological parameters including quantal content altered aging reversed shortterm intermittent fasting methods can used identify potential therapies reverse physiological dysfunction aging,0.0
igg4related autoimmune manifestations alemtuzumabtreated multiple sclerosis patients j neuroimmunol 2021 oct 29 361577759 doi 101016 jjneuroim2021577759 online ahead printabstractwe aimed determine whether alemtuzumabinduced immune reconstitution affects immunoglobulin complement levels serum relapsingremitting multiple sclerosis rrms patients igg4levels increased 24months treatment initiation compared baseline levels twentynine patients alemtuzumabtreated patients highest igg4levels prone thyroidrelated autoimmune manifestations specific autoimmune adverse events crohns disease graves disease hemolytic anemia compared baseline total igglevels showed trend towards reduced levels following twocourses alemtuzumab significant change c3 c4levels observed conclusion monitoring igg4levels can serve marker secondary autoimmunity risk multiple sclerosis patients treated alemtuzumabpmid34742035 doi101016 jjneuroim2021577759,0.0
singlecell transcriptional changes neurodegenerative diseases neuroscience 2021 nov 5s03064522 21 005443 doi 101016 jneuroscience202110025 online ahead printabstractin recent decades understanding molecular changes involved neurodegenerative diseases transformed singlecell rna sequencing singlenucleus rna sequencing technologies applied provide cellular molecular details brain singlecell level expanded knowledge central nervous system provided insights molecular vulnerability brain cell types underlying mechanisms neurodegenerative diseases review highlight recent advances findings related neurodegenerative diseases using cuttingedge technologiespmid34748859 doi101016 jneuroscience202110025,0.0
staff awareness use cannabidiol cbd trustwide survey study uk abstractintroductioncannabidiol cbd now legal substance europe available high street shops usually cbd oil however united kingdom uk clear consensus among healthcare professionals organisations manage cbd use patients important issue cbd constituent medicinal recreational cannabis gaining support scientific literature lay media use physical mental health problems given aforementioned study exploration healthcare professionals beliefs attitudes regard cbdmethodsin july 2018 sent requests email approximately 2000 clinical staff including 319 physicians mental health trust south west london answer 8 questions single survey using surveyplanetcom beliefs regarding cbd specific method choosing staff aim get email request sent many staff possible service line analysis see attitudes beliefs different staff member groups compared also gave space offer free text responses illustrate ideas concerns used chisquared tests comparison across groups used odds ratio pairwise group comparisonsresultsone hundred ninety surveys received response 180 included final sample physician response rate 172 55 319 response rate nonphysicians estimated total number known outset 322 responders right prescribe 58 180 528 experience working addiction services 95 180 found staff members can prescribe 199 times likely believe cbd potential therapeutic properties compared 199 ci 103 382 p 0038 294 times less likely think dangerous side effects 034 ci 015 075 p 0006 prescribing healthcare professionals 23 times likely believe cbd reduces likelihood psychosis 230 ci 110 478 p 0024 however prescribing healthcare professionals ability prescribe 212 times likely believe cbd prescription 212 ci 112 401 p 002 individuals experienced addiction services 222 times likely associated belief cbd therapeutic properties 222 ci 122 404 p 0009 staff general reported lack knowledge cbd free text responsesconclusionswith almost 95 prescribers physicians appear demonstrate awareness potential therapeutic benefit reduced likelihood psychosis seeming lack dangerous side effects cbd however higher stringency need prescription implies attitude caution also suggestion biases cannabis influencing responses questions well external validity study diminished sampling bias limitation single mental health trust nonetheless results drew reasonable comparison similar studies,0.0
eosinophilia natalizumab treatment incidence risk factors temporal patterns j neuroimmunol 2021 sep 29 361577729 doi 101016 jjneuroim2021577729 online ahead printabstracteosinophilia common natalizumab treatment multiple sclerosis risk factors unknown aimed identify demographic clinical laboratory characteristics predicting eosinophilia sustained eosinophilia occurred 168 risk factors sustained eosinophilia included baseline pretreatment eosinophilia medical conditions potentially associated eosinophilia including allergies suboptimal compliance one temporal profile associated highest rapidly developing eosinophilia less likely resolve one case eosinophilia symptomatic changes eosinophil lymphocyte counts weakly correlated suggesting factors late antigen4 vla4 inhibition drive eosinophiliapmid34624660 doi101016 jjneuroim2021577729,0.0
risk factors idiopathic myelitis admission predictors late diagnostic change j neuroimmunol 2021 oct 8 361577747 doi 101016 jjneuroim2021577747 online ahead printabstractimmunemediated myelopathy imm diagnosis challenging etiology may remain unclear despite extensive investigation evaluated diagnostic changes imm patients followup included 80 patients 613 female median followup time 625 months diagnoses discharge 488 multiple sclerosisimm msimm 325 iimm 113 neuromyelitis optica spectrum disordersimm nmosdimm 13 mog encephalomyelitis mogad 62 others imm oimm twentytwo patients 275 changed diagnosis median 155 months 688 msimm 125 nmosdimm 38 mogad 100 iimm 50 oimm patients changed diagnosis iimm predictive factors diagnostic change iimm autonomous gait p 0029 lesions suggestive ms p 0039 higher number lesions p 0043 lesions length 3 vertebral bodies p 0033 cervical involvement p 0038 lower edss admission p 0013 etiologic reclassifications imm common therefore patients require appropriate followup time increase diagnostic accuracypmid34715592 doi101016 jjneuroim2021577747,0.0
humoral immune response multiple sclerosis patients following pfizerbnt162b2 covid19 vaccination 6 months crosssectional study j neuroimmunol 2021 oct 9 361577746 doi 101016 jjneuroim2021577746 online ahead printabstractappropriate immune response following covid19 vaccination important context diseasemodifying treatments dmts prospective crosssectional study determined sarscov2 igg response 6 months following pfizerbnt162b2 vaccination 414 multiple sclerosis ms patients 89 healthy subjects protective response demonstrated untreated ms patients n 76 100 treated cladribine n 48 100 dimethyl fumarate n 35 100 natalizumab n 32 100 teriflunomide n 39 100 similarly healthy subjects n 89 978 response decreased fingolimod n 42 95 ocrelizumab n 114 228 alemtuzumab n 22 864 treated patients igg response can help tailor adequate vaccine guidelines ms patients various dmtspmid34655991 doi101016 jjneuroim2021577746,0.0
development 18f mips15692 radiotracer invitro proofofconcept imaging mer tyrosine kinase mertk neuroinflammatory disease eur j med chem 2021 sep 4 226113822 doi 101016 jejmech2021113822 online ahead printabstractmer tyrosine kinase mertk upregulation associated m2 polarization microglia plays vital role neuroregeneration following damage induced neuroinflammatory diseases multiple sclerosis ms therefore radiotracer specific mertk great utility clinical management ms detection differentiation neuroregenerative neurodegenerative processes study aimed develop 18f ligand high affinity selectivity mertk potential positron emission tomography pet radiotracer mips15691 mips15692 synthesized kinase assays utilized determine potency selectivity mertk compounds shown potent mertk respective ic50 values 46 nm 40 nm also mertkselective plasma brain pharmacokinetics measured mice led selection mips15692 mips15691 xray crystallography used visualize mips15692 recognized enzyme 18f mips15692 synthesized using automated iphase flexlab module molar activity 49 26 gbq mol radiochemical purity 18f mips15692 99 decaycorrected radiochemical yields rcys determined 245 085 brain mertk protein density measured saturation binding assay brain slices cuprizone mouse model ms high levels specific binding 18f mips15692 mertk found especially corpus callosum hippocampus cc hc vivo pet imaging study 18f mips15692 suggested neuropk suboptimal clinical use current efforts underway optimize neuropk next generation pet radiotracers maximal vivo utilitypmid34563964 doi101016 jejmech2021113822,0.0
sexspecific disruption corticospinal excitability hemispheric symmetry multiple sclerosis brain res 2021 oct 8147687 doi 101016 jbrainres2021147687 online ahead printabstractmultiple sclerosis ms neurodegenerative disease pathophysiology symptom progression presents differently sexes cohort people ms n 110 used transcranial magnetic stimulation tms investigate sex differences corticospinal excitability cse sexspecific relationships cse cognitive function although demographics disease characteristics differ sexes males likely cognitive impairment measured montreal cognitive assessment moca 533 compared females 263 greater cse asymmetry noted females compared males females demonstrated higher active motor thresholds longer silent periods hemisphere corresponding weaker hand typical hand dominance patterns healthy individuals males females exhibited asymmetry nerve conduction latency delayed mep latency hemisphere corresponding weaker hand males also relationship delayed onset ipsilateral silent period measured hemisphere corresponding weaker hand moca suggestive crosscallosal disruption findings support sexspecific disruption cse exists ms pointing interhemispheric disruption potential biomarker cognitive impairment target neuromodulating therapiespmid34634288 doi101016 jbrainres2021147687,0.0
clinicoradiological comparative study aquaporin4igg seropositive neuromyelitis optica spectrum disorder nmosd mog antibody associated disease mogad prospective observational study review literature j neuroimmunol 2021 oct 8 361577742 doi 101016 jjneuroim2021577742 online ahead printabstractneuromyelitis optica spectrum disorders nmosd autoimmune inflammatory central nervous system diseases nmosd patients typically recurrent attacks severe optic neuritis myelitis majority autoantibodies aquaporin4 aqp4 recent past robust association autoantibodies fulllength human myelin oligodendrocyte glycoprotein mogigg optic neuritis myelitis brainstem encephalitis well acute disseminated encephalomyelitis adem like presentations demonstrated mogigg antibody associated disease mogad now considered disease entity right distinct classic ms aqp4iggpositive nmosd compared clinical laboratory radiological features treatment outcomes patients aquaporin4igg seropositive nmosd mogad relatively younger age onset lesser number relapses better response treatment favorable clinical outcomes found mogad group comparison aqp4iggpositive nmosd grouppmid34655992 doi101016 jjneuroim2021577742,1.0
age onset predicts outcome aquaporin4igg positive neuromyelitis optica spectrum disorder united kingdom population j neurol sci 2021 oct 24 431120039 doi 101016 jjns2021120039 online ahead printabstractbackground studies exploring prognostic factors patients aquaporin4 aqp4 igg positive neuromyelitis optica spectrum disorder nmosd objective assess predictors outcome patients aqp4antibody positive nmosd united kingdom uk populationmethods retrospective study 52 patients 2 neuroscience centres uk midlandsresults common initial presentations acute myelitis optic neuritis 22 52 cases 423 relapsing course seen 32 patients 615 mean annualised relapse rate 043 standard deviation 045 mean interval time first relapse 31 months range 2108 median expanded disability status scale edss score last follow 4 range 19 age onset independent predictor disability whole cohort patients nmosd every 10year increase age disease onset risk developing edss score 4 increased 34 patients presented initially longitudinally extensive transverse myelitis letm showed higher risk develop disability compared clinical presentations median time 4 years versus 13 years late onset lonmosd patients likely reach edss score 4 quickly compared early onset eonmosd median time 7 years versus 13 years higher median edss score last follow observed lonmosd compared eonmosd 6 versus 2 conclusion increasing age onset letm predict disability aqp4igg positive nmosd patientspmid34715481 doi101016 jjns2021120039,0.0
stat3 inhibitor mitigates cerebral amyloid angiopathy parenchymal amyloid plaques improving cognitive functions brain networks abstractprevious reports indicate potential role signal transducer activator transcription 3 stat3 amyloid processing neuritic plaque pathogenesis present study impact stat3 inhibition cognition cerebrovascular function amyloid pathology oxidative stress neuroinflammation studied using vitro vivo models alzheimers disease ad related pathology vitro experiments human brain vascular smooth muscle cells hbvsmc human brain microvascular endothelial cells hbmec used cultured cells exposed peptides followed measurement activated forms stat3 expression reactive oxygen species ros generation 6 months old 5xfad apoe4 5xe4 mice agematched negative littermates used vivo experiments mice treated stat3 specific inhibitor lll12 2 months followed neurobehavioral histopathological assessment vitro experiments showed exposure cerebrovascular cells peptides upregulated activated forms stat3 produced stat3mediated vascular oxidative stress 5xe4 mice treated stat3specific inhibitor lll12 improved cognitive functions functional connectivity augmented cerebral blood flow functional improvements associated reduction neuritic plaques cerebral amyloid angiopathy caa oxidative stress neuroinflammation reduction amyloid precursor protein app processing attenuation oxidative modification lipoprotein receptor related protein1 lrp1 identified potential underlying mechanisms results demonstrate broad impact stat3 cognitive functions parenchymal vascular amyloid pathology highlight therapeutic potential stat3 specific inhibition treatment ad caa,1.0
causal role high body mass index multiple chronic diseases systematic review metaanalysis mendelian randomization studies background obesity worldwide epidemic associated plurality diseases observational studies aim study summarize evidence mendelian randomization mr studies association body mass index bmi chronic diseasesmethodspubmed embase searched mr studies adult bmi relation major chronic diseases including diabetes mellitus diseases circulatory respiratory digestive musculoskeletal nervous systems neoplasms metaanalysis performed disease using results published mr studies corresponding de novo analyses based summarylevel genetic data finngen consortium n 218 792 individuals resultsin metaanalysis results published mr studies de novo analyses finngen consortium genetically predicted higher bmi associated increased risk type 2 diabetes mellitus 14 circulatory disease outcomes asthma chronic obstructive pulmonary disease five digestive system diseases three musculoskeletal system diseases multiple sclerosis well cancers digestive system six cancer sites uterus kidney bladder contrast genetically predicted higher adult bmi associated decreased risk dupuytrens disease osteoporosis breast prostate nonmelanoma cancer associated alzheimers disease amyotrophic lateral sclerosis parkinsons diseaseconclusionsthe totality evidence mr studies supports causal role excess adiposity plurality chronic diseases hence continued efforts reduce prevalence overweight obesity major public health goal,0.0
evolution prediction mismatch observed perceived upper limb function stroke prospective longitudinal observational cohort study background previously shown mismatch group patients good observed upper limb ul motor function low perceived ul activity six months post stroke tends use affected ul less daily life expected based clinical tests mismatch may also present 12 months aimed confirm group another cohort investigate evolution group six 12 months determine factors admission inpatient rehabilitation 6 months can discriminate mismatch good match groups 12 monthsmethodspersons stroke recruited rehabilitation admission reassessed six 12 months observed ul function measured upper extremity subscale fuglmeyer assessment fmaue perceived ul activity hand subscale stroke impact scale 30 sishand defined mismatch good observed ul function fmaue 50 66 low perceived activity sishand75 100 potential discriminators admission 6 months demographic characteristics stroke characteristics ul somatosensory function cognitive deficits mental function activity statistically compared match mismatch groups 12 monthsresultswe included 60 participants female 42 mean sd age 65 12 years confirmed mismatch group 11 18 patients 6 months increased 14 23 patients 12 months mismatch group compared good match group 12 months patients higher stroke severity somatosensory impairments admission 6 monthsconclusionswe confirmed group patients good observed ul function low perceived activity six 12 months post stroke assessment stroke severity somatosensory impairments admission rehabilitation determine mismatch 12 months might warrant intervention however large differences clinical outcomes patients mismatch group indicate importance tailoring training individual needs,0.0
biocompatible injectable hydrogel boost efficacy stem cells neurodegenerative diseases treatment life sci 2021 oct 27120108 doi 101016 jlfs2021120108 online ahead printabstractaims stem cell therapies emerged treatment modalities potential cure neurodegenerative diseases nds however despite high expectations clinical use still limited critical issues treatment outcomes may related stem cells formulation administration route develop hydrogel cell carrier consisting compounds phospholipids hyaluronic acidha naturally present central nervous system cns habased hydrogel physically crosslinked liposomes designed direct injection cns significantly increase bone marrow mesenchymal stem cells bmscs bioavailabilitymaterials methods hydrogel compatibility confirmed vitro bmscs vivo intracerebroventricular injection rats assess efficacy main cause chronic neurologic disability young adults selected namely multiple sclerosis ms efficacy developed formulation containing lower number cells previously reported demonstrated using experimental autoimmune encephalomyelitis eae rat modelkey findings distribution engineered hydrogel corpus callosum can ideal nds treatment since damage white matter structure responsible important neuronal deficits moreover bmscsladen hydrogel significantly decreases disease severity maximum clinical score eliminated relapsesignificance engineering advanced therapies using natural carrier can result efficacious treatments ms related debilitating conditionspmid34717909 doi101016 jlfs2021120108,0.0
neuronal cardiac toxicity pharmacological compounds identified transcriptomic analysis human pluripotent stem cellderived embryoid bodies toxicol appl pharmacol 2021 nov 3115792 doi 101016 jtaap2021115792 online ahead printabstractconcurrent 3r principle embryonic stem cell test est using mouse embryonic stem cells developed 2000 remains solely accepted vitro method embryotoxicity testing however scope implementation est embryotoxicity screening compliant regulatory requirements limited due technical complexity long testing period laborintensive methodology limited endpoint data leading misclassification embryotoxic potential study used human induced pluripotent stem cell hipsc derived embryoid bodies eb vitro model investigate embryotoxic effects carefully selected set pharmacological compounds morphology viability differentiation potential investigated exposing ebs folic acid alltransretinoic acid dexamethasone valproic acid 15 days results showed compounds differentially repressed cell growth compromised morphology triggered apoptosis ebs transcriptomics employed compare subtle temporal changes treated untreated cultures gene ontology pathway analysis revealed dysregulation large number genes strongly correlated impaired neuroectoderm cardiac mesoderm formation aberrant gene expression pattern associated several disorders brain like mental retardation multiple sclerosis stroke heart like dilated cardiomyopathy ventricular tachycardia ventricular arrhythmia lastly vitro findings validated using ovo chick embryo model taken together pharmacological compound druginduced defective eb development hipscs potentially used suitable vitro platform embryotoxicity screeningpmid34742744 doi101016 jtaap2021115792,0.0
health care professionals perspectives selfmanagement people parkinsons qualitative findings uk study background parkinsons disease longterm complex health condition improve maintain quality life people parkinsons can active involvement care selfmanagement techniques given complexity individualization selfmanagement people parkinsons will need support encouragement healthcare professionals hcps despite key role hcps research seldom explored perspectives understanding selfmanagement people parkinsonsmethodsmultidisciplinary teams providing care people parkinsons across london coventry hertfordshire approached took part either one four focus groups individual interviews fortytwo hcps including range specialist doctors general practitioners allied health professionals nurses social workers took part study interviews transcribed analysed using thematic analysis identify themesresultsfour themes developed data 1 empowerment patients holistic care personcentred 2 maximising motivation capability patients example using asset based approaches increasing opportunities 3 importance empowerment carers support selfmanagement 4 contextual barriers selfmanagement social contextconclusionsthis study first explore perspectives hcps selfmanagement people parkinsons findings identified important considerations surrounding empowerment motivation carers contextual barriers better understand enable effective selfmanagement techniques people parkinsons research build findings develop acceptable effective selfmanagement tools use practice people affected parkinsons,0.0
cgassting signaling pathway gastrointestinal inflammatory disease cancers abstractcyclic gmpamp synthase cgas stimulator interferon genes sting signaling pathway emerged key dnasensing machinery innate immunity activation cgassting signaling pathway mediates production interferons proinflammatory cytokines although cgassting signaling pathway shows critical function maintenance gut homeostasis overactive cgassting signaling pathway leads gastrointestinal gi inflammation harnessing effect mechanism cgassting signaling pathway beneficial development novel strategies treatment gi diseases review presents recent advances regarding role cgassting signaling pathway gi inflammatory disease cancers describes perspective therapeutic strategies targeting signaling pathway,0.0
atypical drainage persistent left vena cava superior left atrial appendage detected multidimensional imaging acase report review literature background common thoracic venous anomaly persistent left vena cava superior may present atypical variations important consider clinical managementcase presentationhere report 35yearold caucasian female patient drainage left atrial appendage presented shortness breath accompanied mild hypoxemia venous contrast filling context pulmonary scintigraphy suspected additional superior caval vein connected left atrial appendage diagnosis confirmed transesophageal echocardiography cardiac catheterization revealed minor righttoleft shunt symptoms allocated bronchial asthma treated according guidelines cerebral lesions detected patient due coincident multiple sclerosis rather cerebral embolisms thus venous anomaly classified incidental finding currently requiring treatmentconclusionsto best knowledge first report persistent left vena cava superior draining left atrial appendage,0.0
pediatric tizanidine toxicity reversed naloxone case report background tizanidine 2 adrenoceptor agonist widely prescribed management spasticity adults case reports pediatric tizanidine overdose limited report case pediatric tizanidine toxicity reversed naloxonecase presentationa 3yearold male presented emergency department lethargy bradycardia bradypnea accidental ingestion multiple tizanidine tablets improvements level consciousness respiratory heart rates observed two intravenous administrations naloxone dose 005 01 mg kg respectivelyconclusionsthis case report provides evidence regarding use naloxone viable antidote centrally acting 2 receptor agonists presents additional epidemiologic data childhood tizanidine poisoning,0.0
impact comorbidities risk angioedema without urticaria elderly patients background angioedema without urticaria awu disease found elderly population still poorly studied aim study investigate potential factors especially comorbidities may affect induction angioedema without urticaria patients 60 years agemethodsthis observational retrospective study 242 patients diagnosis awu 263 controls inclusion criteria follows least one episode confirmed awu based icd10 code t783 required treatment last 15 years 20042019 age 60 years detailed medical history comorbidities details regarding use drugs time serum functional quantitative c1 inhibitor assays performed serum c4 measuredcomorbidities grouped following panels autoimmune cancer cardiac metabolic respiratory allergic liver failure renal failure individual diseases checked according icd code treatmentresultsin 1 04 patient hereditary angioedema confirmed decreased levels c1inh observed 4 165 patients dysfunction c1inh observed 5 176 patients low levels c4 observed 9 371 patients study group multiple logistic regression model revealed patients hyperuricemia hashimotos disease significantly higher chance angioedema 321 95 ci 292366 p 0002 178 95 ci 137221 p 0034 respectively conclusionthe obtained results may indicate significant influence hyperuricemia hashimotos disease angioedema manifestations,0.0
conflictrelated health research syria 20112019 scoping review lancet aub commission syria background volume healthrelated publications syria increased considerably course conflict compared prewar period increase largely attributed commentaries news reports editorials rather research publications paper seeks characterise conflictrelated population humanitarian health health systems research focused inside syria published course syrian conflictmethodsas part broader scoping review covering english arabic french literature health syria published 01 january 2011 31 december 2019 indexed seven citation databases pubmed medline ovid cinahl complete global health embase web science scopus analyzed conflictrelated research papers focused health issues inside syria syrians residents syria classified research articles based major thematic areas studied abstracted bibliometric information study characteristics research focus funding statements key limitations challenges conducting research described study authors gain additional insights examined separately nonresearch publications reporting field operational activities well personal reflections narrative accounts firsthand experiences inside syriaresultsof 2073 papers identified scoping review 710 34 exclusively focus health issues syrians residents inside syria 350 49 conflictrelated including 89 25 research papers annual volume research increased time one publication 2013 26 publications 2018 29 2019 damascus frequently studied governorate n 33 followed aleppo n 25 papers used wide range research methodologies predominantly quantitative n 68 country institutional affiliation s first last authors predominantly syria n 30 21 respectively united states n 25 19 respectively united kingdom n 12 10 respectively majority authors academic institutional affiliations frequently examined themes health status health system humanitarian assistance response needs n 38 34 26 respectively authors described range contextual methodological administrative challenges conducting research health inside syria thirtyone publications presented field operational activities eight publications reflections firsthand personal accounts experiences inside syriaconclusionsdespite growing volume research publications examining population humanitarian health health systems issues inside conflictravaged syria considerable geographic thematic gaps including limited research several key pillars health system governance financing medical products issues injury epidemiology noncommunicable disease burden situation northeast south syria besieged areas populations recognising myriad complexities researching active conflict settings essential research syria continues order build evidence base understand critical health issues identify knowledge gaps inform research agenda address needs people syria following decade conflict,0.0
value willingness pay qaly gained iran modified chainedapproach background due lack constant willingness pay per one additional quality adjusted life years gained based preferences irans general public costeffectiveness health system interventions unclear making challenging apply economic evaluation health resources priority settingmethodswe measured costeffectiveness threshold participation 2854 individuals five provinces representing income quintile using modified time tradeoffbased chainedapproach onlinebased empirical survey extract health utility value participants randomly assigned one two green 21121 yellow 22222 health scenarios designed based earlier validated eq5d3l questionnaireresultsacross two health state versions mean values one qaly gain rounded ranged 67407400 64807120 respectively aggregate trimmed models equivalent 135118 times gdp per capita loglinear multivariate ols regression analysis confirmed respondents likely pay income disutility education level higher counterpartsconclusionsin health system iran intervention incremental costeffectiveness ratio equal less 740212 usd will considered costeffective,0.0
gut microbiota modulation possible mediating mechanism fastinginduced alleviation metabolic complications systematic review background intermittent fasting reported positive effects obesity diabetes cardiovascular diseases hypertension several neurodegenerative diseases different mechanisms alteration gut microbiota systematic review conducted aim providing overview existing animal human literature regarding gut microbiota alterations various fasting regimensmethoda systematic literature search conducted pubmed scopus web science databases may 2021 find relevant studies examining gut microbiota alteration fasting original researches animal models human patients included studyresultsthe search fulfilled 3072 documents 31 studies 20 animal 11 human studies included upon fasting abundance several beneficial bacteria including lactobacillus bifidobacterium shifted significantly moreover taxa including odoribacter negatively associated blood pressure bloomed fasting ramadan fasting kind intermittent fasting improves health parameters positive changes gut microbiota including upregulation muciniphila b fragilis bacteroides butyric acidproducing lachnospiraceaeconclusionthe findings suggest different fasting regimens including alternateday fasting calorie timerestricted fasting programs ramadan fasting promote health maybe modulation gut microbiome however studies needed explore properly connection gut microbiota meal frequency timing,0.0
tetrandrine alleviates podocyte injury via calciumdependent calpain1 signaling blockade background podocytes become crucial target interventions proteinuric kidney diseases many studies reported overexpression transient receptor potential cation channel protein 6 trpc6 podocyte injury upregulates intracellular ca2+ influx stimulates ca2+dependent protease calpain1 signaling traditional chinese drug tetrandrine nonselective ca2+ channel blocker long used treat chronic kidney disease research aimed explore possible mechanisms underlying antiproteinuric properties tetrandrinemethodswe investigated involvement tetrandrine ca2+ dependent calpain1 signaling mouse podocytes adriamycininduced nephropathy rats cyclosporine csa u73122 used positive controls cell viability cytotoxicity ca2+ concentration calpain activity mrna protein expression levels calpain1 signaling pathways examined clinical pathological changes measuredresultstetrandrine decreased intracellular ca2+ influx cultured trpc6overexpressing podocytes vitro vivo studies administration tetrandrine downregulated calpain activity expression calpain1 restored expression downstream talin1 nephrin compared csa tetrandrine treatment exhibited superior inhibitory effects calpain activity calpain1 expressionconclusionstetrandrine therapeutic potential podocyte damage blocking ca2+dependent activation calpain1 signaling pathway tetrandrine reduced proteinuria improved renal function alleviate renal pathological damage,0.0
tnf plays crucial role inflammation signaling via t cell tnfr2 proc natl acad sci u s 2021 dec 14 118 50 e2109972118 doi 101073 pnas2109972118abstracttnf produced largely t innate immune cells potently proinflammatory cytokines ifn il17 produced th1 th17 cells respectively asked tnf upstream th skewing toward inflammatory phenotypes exposure mouse cd4+ t cells tnf tgf generated th17 cells express low levels il17 rort+il17lo high levels inflammatory markers independently il6 stat3 mediated nondeath tnf receptor tnfr2 also contributed generation inflammatory th1 cells singlecell rna sequencing central nervous systeminfiltrating cd4+ t cells mouse experimental autoimmune encephalomyelitis eae found inflammatory gene expression profile similar cerebrospinal fluidinfiltrating cd4+ t cells patients multiple sclerosis notably tnfr2deficient cd4+ t cells produced fewer inflammatory mediators less pathogenic eae colitis il1 th17skewing cytokine induced tnf proinflammatory granulocytemacrophage colonystimulating factor gmcsf t cells inhibited disruption tnfr2 signaling demonstrating il1 can function indirectly via production tnf thus tnf just effector also initiator inflammatory th differentiationpmid34873037 doi101073 pnas2109972118,0.0
im walking unknown qualitative insights emotions lived experience related multiple sclerosis diagnosis impact decisions pursue disease modifying treatment abstractintroduction people relapsing remitting multiple sclerosis rrms increasingly included active participants shared decision making around treatment options choosing first disease modifying treatment dmt complex process often takes place soon diagnosis given patients therefore often required make difficult decisions time still coming terms illness study investigated views experiences recently diagnosed patients rrms making initial dmt choicemethod qualitative study involving indepth semistructured interviews patients rrms national health service nhs setting united kingdom data collected 6 patients analysis guided interpretive phenomenological analysis ipa approachresults initial reactions diagnosis characterized strong emotions feeling despair hopelessness subsequently dmt decision shaped multiple considerations around maintaining normality restoring hope control onenulls life whilst reconciling uncertainty around efficacy considering future dmt elicited reflections around employment family planningconclusion emotions lived experience related recent ms diagnosis can impact initial dmt decision number ways health care professionals need understand lived experience patients making dmt decisions soon diagnosis engaging shared decision making,0.0
estimating prevalence human traits among populations polygenic risk scores abstractthe genetic basis phenotypic variation across populations well explained traits several factors may cause disparities variation environments divergent population genetic structure hypothesized populationlevel polygenic risk score prs can explain phenotypic variation among geographic populations based solely risk allele frequencies applied populationspecific prs psprs 26 populations 1000 genomes four phenotypes lactase persistence lp melanoma multiple sclerosis ms height models assumed additive genetic architecture among polymorphisms psprss convention linear psprss explained significant proportion trait variance ranging 032 height men 088 melanoma best models lp height linear melanoma ms nonlinear variants prs may confer similar even risk among diverse populations also filtered snps assess whether variance explained improved using psprss fewer snps variance explained usually improved fewer snps psprs high 099 height men using 548 initial 4208 snps reducing snps improves psprss performance may indicate missing heritability partially due complex architecture mandate additivity undiscovered variants spurious associations databases demonstrated prsbased analyses can used across diverse populations phenotypes population prediction comparisons can identify universal risk variants,0.0
spectrum biopsyproven glomerular diseases tertiary hospital southern brazil background prevalence distribution glomerular diseases differ among countries indication perform kidney biopsy varies among centres study assessed prevalence primary secondary glomerulopathies based histological diagnoses correlation glomerulopathies demographic clinical data evaluatedmethodsin study 1051 kidney biopsies retrospectively reviewed 2000 2018 patient demographic clinical laboratory data assessed prevalence primary glomerulonephritis pg secondary glomerulopathies sg well tubulointerstitial diseases tids hereditary nephropathies hns diagnoses determined frequency primary secondary glomerulopathies evaluated age group temporal variation frequencies across three time periods 20002005 20062011 20122018 reportedresultsthe prevalence sg predominated 524 followed pg 296 diagnoses 107 tid 66 hn 11 among primary forms glomerular disease focal segmental glomerulosclerosis fsgs common 373 followed iga nephropathy igan 244 membranous nephropathy mn 186 minimal change disease mcd 84 lupus nephritis ln 411 common patients sg followed diabetic kidney disease dkd 178 systemic vasculitis sv 102 secondary fsgs 2nd fsgs 10 nephrotic syndrome common clinical presentation patients pg also patients drd 2nd fsgs whereas patients igan sv nephritic syndrome main presentation age group 18 50 years ln fsgs igan predominated patients aged 51 65 years proportion dkd 2nd fsgs increased sv common patients 65 years temporal variation pg across three time periods showed statistically significant increase igan p 0001 reduction fsgs time p 0001 sg reduction ln p 0027 increase dkd p 0001 time tendency 2nd fsgs decrease time p 0053 conclusionsin studied kidney biopsy registry fsgs igan prevalent diagnoses patients pg ln dkd prevalent patients sg nephrotic syndrome major indication biopsy comparing temporal variation glomerulopathies reduction fsgs increase igan patients pgs time patients sgs reduction ln increase cases dkd time,0.0
symptom rates profile clustering tuberous sclerosis complexassociated neuropsychiatric disorders tand background tuberous sclerosis complex tsc associated range neuropsychiatric difficulties appropriately termed tscassociated neuropsychiatric disorders tand objectives study analyze rates tand symptoms cohort patients seen tsc center excellence cincinnati childrens hospital identify clinically meaningful profiles based tand symptomsmethodsdata tand checklist obtained participants seen tsc center excellence cincinnati childrens hospital medical center june 2015 august 2018 cluster factor analyses tand symptom performed factor scores calculated participants kmeans cluster analysis scores used empirically identify distinct overall tand symptom profiles occurring tscresultsa total 1545 checklists completed 668 participants 37 adults 63 children approximately 90 participants reported least one tand symptom average 12 symptoms 29 symptom rates ranged 5 60 common symptoms neuropsychologic symptoms sevencluster sevenfactor solution found optimal kmeans cluster analysis resulted sevenprofile solution ranging low high symptom burdenconclusionthis study first identify natural phenotypic profiles tand symptoms study specific tand subpopulations shared profiles may facilitate better understanding underlying biology tand better assessment targeted treatments,0.0
seasonal variation attacks neuromyelitis optica spectrum disorders multiple sclerosis evaluation 794 attacks nationwide registry argentina abstractbackground identification triggers potentially instigate attacks neuromyelitis optica spectrum disorders nmosd multiple sclerosis ms remained challenging aimed analyze seasonality nmosd ms attacks argentinean cohort seeking differences two disordersmethods retrospective study conducted cohort nmosd ms patients followed specialized centers argentina enrolled relevarem nationwide longitudinal observational nonmandatory registry ms nmosd patients patients complete relapse data date month year onset followup included attack counts analyzed month using poisson regression model median monthly attack count used referenceresults total 551 patients 431 ms 120 nmosd experiencing 236 nmosdrelated attacks 558 msrelated attacks enrolled mean age disease onset nmosd 395 58 vs 312 96 years ms p001 mean followup time 61 30 vs 74 24 years p001 respectively included patients female groups 79 vs 60 p001 found peak number attacks june nmosd 28 attacks 118 vs ms 33 attacks 59 incidence rate ratio 182 95ci 115212 p003 differences found across months disorders evaluated separately strikingly observed significant difference incidence rate ratio attacks winter season comparing nmosd vs ms nmosd 75 attacks 317 vs ms 96 attacks 172 incidence rate ratio 182 95ci 121201 p002 applying poisson regression model similar results observed comparing seropositive nmosd n75 subgroup vs msconclusions lack seasonal variation ms nmosd attacks observed evaluated separately future epidemiological studies effect different environmental factors ms nmosd attacks evaluated prospectively latin america population,0.0
noncommunicable diseases southwest iran profile baseline data shahrekord persian cohort study background critical interprovincial differences within iran pattern noncommunicable diseases ncds difficulties inherent identifying prevention methods reduce mortality ncds challenged implementation provincial health system plan shahrekord cohort study scs designed address gaps chaharmahal bakhtiari province high altitude southwest iran characterized large bakhtiari population along fars turk ethnicity groupsmethodsthis ongoing cohort prospective largescale longitudinal study includes unique rich biobank conducted first time chaharmahal bakhtiari province iran scs part persian prospective epidemiological research studies iran cohort study began 2015 recruited 10075 participants 528 female 472 male urban n7034 rural n3041 areas participants will annually followed least 15 years crosssectional analysis conducted using baseline data scs using descriptive statistics logistic regression data analysis performed using stata softwareresultsthe prevalence ncds 98 type 2 diabetes 171 hypertension 116 thyroid disease 02 multiple sclerosis 57 09 13 ischemic heart disease stroke myocardial infarction respectively prevalence multimorbidity 2 ncds higher women 391 men 249 means standard deviations age bmi systolic blood pressure fasting blood glucose 495 9 years 276 46 kg m2 1154 173 mmhg 967 273 mg dl respectively logistic regression models showed older age female gender living urban area nonnative ethnicity high wealth index unemployment obesity low physical activity hypertriglyceridemia high fasting blood sugar alkaline urine ph high systolic diastolic blood pressure associated increased prevalence ncdsconclusionsthe scs provides platform epidemiological studies will useful better control ncds southwest iran foster research collaboration scs will essential resource identifying ncd risk factors region designing relevant public health interventions,0.0
case report chadox1 ncov19 vaccineassociated encephalitis background vaccination covid19 continues apace sideeffects common severe continue reported report first published case covid19 vaccinerelated encephalitiscase presentationa young woman presented acute neuropsychiatric symptoms following recent chadox1 ncov19 vaccination extensive investigation identify alternative causesconclusionsthis difficult case described including presentation investigation management study neuropsychiatric sideeffects covid19 vaccination including investigation whether may causal link required,0.0
neglected aspect points deal cognitive disorders people multiple sclerosis eagerly read article mahmoudi et al 2021 article examined prevalence alzheimernulls related dementia adrd people multiple sclerosis ms indicated rate alzheimernulls disease people ms significantly higher normal population rate increases age article presented important aspect cognitive impairment people ms known long time cognitive impairment common patients 40 70 suffer impairment alfalaki et al 2021 also understood conditions worsened time katsari et al 2020 even individuals ms progression illnesses may fast can quickly lead dementia naser moghadasi sahraian 2020 despite results cognitive impairment remains overlooked minor concern treatment ms according mahmoudi et al patients become older development adrd becomes severe hazard issue might caused part failure pay attention cognitive impairments people younger furthermore little effort made eliminate control risk factors cognitive disorders caused ms alzheimernulls people cognitive rehabilitation important part treatment cognitive disorders individuals still marginal issue however points indicate need guidelines treatment cognitive disorders people ms guidelines answer basic questions regard provide practical advice physicians treatment cognitive disorders important unanswered question field necessity nonnecessity changing diseasemodifying drugs dmds patients suffer cognitive disorders without manifestation physical condition usual goal treatment person ms prevent relapse disease progression disability increase new plaques magnetic resonance imaging mri increase brain atrophy patients although cognitive impairment may cause significant disability yet used criterion altering medication questions resolved include whether need periodic cognitive assessment individuals similar mri test distance employed cognitive rehabilitation considered management people although dmds necessary almost individuals diagnosed ms given according mahmoudi et al seems cognitive rehabilitation considered essential part treating ms outset administration dmds,0.0
novel biomimetic nanomedicine system antiinflammatory antiosteoporosis effects improves therapy efficacy steroidresistant nephrotic syndrome abstractclinically steroidresistant nephrotic syndrome srns always prolonged difficult treat easily develops endstage renal disease resulting low survival rate strategies reverse steroid resistance reduce longterm use high doses steroid medicines urgently needed study novel nanoparticle drug system pmgch coreshell structure designed metalorganic frameworks synthesized glycyrrhizic acid g calcium ions ca2+ loaded hydrocortisone h core nanoparticles platelet membrane vesicles shells natural platelet membrane endows pmgch good biocompatibility ability promote immune escape addition chemotaxis inflammatory factors platelet membranes assist pmgch nonspecific targeting inflammatory sites kidney inflammatory acid environment gch slowly degrades releases glycyrrhizic acid hydrocortisone glycyrrhizic acid inhibits inactivation hydrocortisone jointly inhibits activity phospholipase a2 pla2 classic activation pathway complement c2 blocks production inflammatory factors plays antiinflammatory role enhances efficacy hydrocortisone treatment srns moreover glycyrrhizic acid alleviates osteoporosis induced longterm use glucocorticoids results indicate pmgch promising treatment strategy srnsgraphical abstract,0.0
endothelial sphingosine1phosphate receptor 4 regulates bloodbrain barrier permeability promotes homeostatic endothelial phenotype precise regulation bloodbrain barrier bbb permeability immune cells bloodborne substances essential maintain brain homeostasis sphingosine1phosphate s1p lipid signaling molecule enriched plasma known affect bbb permeability previous studies focussed endothelial s1p receptors 1 2 reporting barrierprotective effect s1p1 barrierdisruptive effect s1p2 present novel data characterizing expression localization function s1p receptor 4 s1p4 primary brain microvascular endothelial cells bmecs hitherto receptor deemed exclusively immune cellassociated detected robust expression s1p4 homeostatic murine bovine porcine bmecs pinpointed localization abluminal endothelial membranes via immunoblotting fractionated brain endothelial membrane fragments apical s1p treatment bmecs tightened endothelial barrier vitro whereas basolateral s1p treatment led increased permeability correlated s1p4 downregulation likewise downregulation s1p4 observed mouse brain microvessels stroke neurological disease associated bbb impairment rna sequencing qpcr analysis bmecs suggested involvement s1p4 endothelial homeostasis barrier function using s1p4 ko mice s1p4 sirna well pharmacological agonists antagonists s1p4 vitro vivo demonstrate overall barrierprotective function s1p4 therefore suggest s1p4 novel target regulating bbb permeability propose therapeutic potential cns diseases associated bbb dysfunctionsignificance statementmany neurological diseases including multiple sclerosis stroke associated bbb impairment disturbed brain homeostasis sphingosine1phosphate receptors s1prs potent regulators endothelial permeability pharmacological s1pr modulators already clinical use however precise role s1p bbb permeability regulation function receptors s1p1 s1p2 therein still unclear study shows barrierdisruptive barrierprotective effects s1p bbb depend receptor polarization demonstrate expression novel barrierprotective function s1p4 brain endothelial cells pinpoint localization abluminal membranes work may contribute development novel specific s1pr modulators treatment neurological diseases associated bbb impairment,0.0
serological markers exploration realword effectiveness safety teriflunomide south chinese patients multiple sclerosis abstractbackground since september 2012 teriflunomide approved diseasemodifying treatment relapsing multiple sclerosis realworld observational studies teriflunomide chinese patients limitedmethods collected demographic characteristics peripheral blood samples different time points clinical symptoms magnetic resonance imaging data concentrations neurofilament light chains multiple cytokines different time points compared assess efficacy moreover safety assessed blood routine liver kidney function questionnaire report adverse reactionsresults teriflunomide significantly reduced serum levels neurofilament light chains several inflammatory cytokines accepting teriflunomide treatment many clinical symptoms improved scores expanded disability status scale decreased 20 175 annualized relapse rates decreased 145 031 29 8056 15 7895 patients achieved evidence disease activity3 status 6 months 12 months treatment respectively teriflunomide associated mild moderate discomfort discontinuation rates due adverse events lowconclusions serum neurofilament light chain protein sensitive teriflunomide treatment suggesting potential used indicator assess efficacy teriflunomide teriflunomide can significantly reduce concentrations inflammatory cytokines indicating teriflunomide may regulate neuroinflammation inhibitory effect variety immune cells cytokines teriflunomide can improve clinical symptoms disease severity ms patients southern china patients good compliance,0.0
transient hypertriglyceridemia common finding epsteinbarr virusinduced infectious mononucleosis background hypertriglyceridemia can occur lymphoproliferative disorders infectious mononucleosis selflimiting benign lymphoproliferative disorder study aimed investigate serum triglyceride concentrations change time patients infectious mononucleosismethodswe evaluated adult patient severe hypertriglyceridemia 1000 mg dl infectious mononucleosis reviewed records 360 patients admitted hospital infectious mononucleosis median age 19 years range 1587 years 514 male compared serum triglyceride concentrations control sample general population n75 second triglyceride measurement obtained convalescence median 30 days initial determination available 160 patientsresultsthe triglyceride concentrations acute phase median 156 mg dl significantly higher controls median 76 mg dl p0001 total 194 539 patients presented hypertriglyceridemia 150 mg dl common patients older 30 years younger patients 786 vs 506 p0001 significant correlation p0005 observed triglyceride levels white blood cell counts total cholesterol levels liver damage markers triglyceride concentrations decreased convalescence p0001 lower initial measurement 837 cases conversely total cholesterol concentrations acute phase lower controls increased convalescence p0001 conclusionspatients severe infectious mononucleosis frequently show mild transient hypertriglyceridemia studies needed elucidate mechanisms underlying finding,0.0
brutons tyrosine kinase drives neuroinflammation anxiogenic behavior mouse models stress background current therapies targeting several neurotransmitter systems able partially mitigate symptoms stress traumarelated disorder stress traumarelated disorders lead prominent inflammatory response humans preclinical models however mechanisms underlying induction neuroinflammatory response ptsd anxiety disorders clearly understood present study investigated mechanism underlying activation proinflammatory nlrp3 inflammasome il1 mouse models stressmethodswe used two mouse models stress ie mice subjected physical restraint stress brief underwater submersion predator odor stress mice injected mcc950 small molecule specific inhibitor nlrp3 activation pharmacologically inhibit btk specific inhibitor ibrutinib used validate observation ibrutinib studies separate group mice injected another btkspecific inhibitor lfma13 seven days induction stress mice examined anxious behavior using open field test oft lightdark test ldt elevated plus maze test epm following behavior tests hippocampus amygdale extracted analyzed various components nlrp3caspase 1il1 pathway plasma peripheral blood mononuclear cells also used assess induction nlrp3caspase 1il1 pathway stressed miceresultsusing two different preclinical models stress demonstrate heightened anxious behavior female mice compared male counterparts stressed animals exhibited upregulation proinflammatory il1 il6 caspase 1 activity nlrp3 inflammasome activation brain significantly higher female mice pharmacological inhibition nlrp3 inflammasome activation led anxiolysis well attenuated neuroinflammatory response observed induction activated brutons tyrosine kinase btk upstream positiveregulator nlrp3 inflammasome activation hippocampus amygdala stressed mice next conducted proofofconcept pharmacological btk inhibitor studies ibrutinib lfma13 sets experiments found btk inhibition led anxiolysis attenuated neuroinflammation indicated significant reduction nlrp3 inflammasome proinflammatory il1 hippocampus amygdala analysis plasma peripheral blood mononuclear cells indicated peripheral induction nlrp3caspase 1il1 pathway stressed miceconclusionour study identified btk key upstream regulator neuroinflammation drives anxiogenic behavior mouse model stress demonstrated sexually divergent activation btk providing clue heightened neuroinflammation anxiogenic response stress females compared male counterparts data pharmacological inhibition studies suggest btk novel target development potential clinical treatment ptsd anxiety disorders induction pbtk nlrp3 peripheral blood mononuclear cells stressed mice suggest potential effect stress systemic inflammation,0.0
effect preoperative ct angiography examination clinical outcome patients bmi 250kg#x2f m2 undergoing laparoscopic gastrectomy study protocol multicentre randomized controlled trial background gastric cancer fifth common malignancy third common cause cancerrelated death particularly predominant east asian countries china japan korea serious global health issue causes heavy financial burden government family knowledge reports multicentre randomized controlled trials utilization ct angiography cta patients histologically diagnosed gastric cancer surgery therefore planned rct verify whether utilization cta can change short longterm clinical outcomesmethodthe gissg 2001 study multicentre prospective openlabel clinical study emphasises application cta patients will undergo laparoscopic gastrectomy prove clinical findings total 382 patients meet inclusion criteria will recruited study randomly divided two groups 11 ratio cta group n 191 noncta group n 191 groups will undergo upper abdomen enhanced ct cta group will also receive ct angiography primary endpoint trial volume blood loss second primary endpoints number retrieved lymph nodes postoperative recovery course hospitalization costs length hospitalization days postoperative complications 3year os 3year dfsdiscussionit anticipated results trial will provide highlevel evidence clinical value application cta laparoscopic gastrectomytrial registrationclinicaltrialsgov nct04636099 registered november 19 2020,0.0
update pathogenesis diagnosis flow normoalbuminuric diabetes renal insufficiency abstractin recent decades prevalence diabetic kidney disease remained stable appears wide heterogeneity normoalbuminuric diabetes renal insufficiency characterized decline glomerular filtration rate absence albuminuria identified albuminuriaindependent phenotype diabetic kidney disease epidemiological data demonstrate normoalbuminuric phenotype prevalent compared albuminuric phenotype normoalbuminuric phenotype distinct clinical characteristics wide heterogeneity pathological features currently pathogenesis normoalbuminuric phenotype remains unclear additionally flow diagnosing normoalbuminuric phenotype perfect article review latest studies addressing epidemiology clinical characteristics pathology normoalbuminuric phenotype based studies clinical features renal histopathologic changes attempt propose underlying pathogenesis model flow chart diagnosing normoalbuminuric phenotype,0.0
little things big evaluation compassionate community approach promoting health vulnerable persons background vulnerable persons individuals whose life situations create exacerbate vulnerabilities low income housing insecurity social isolation vulnerable people often receive patchwork health social care services appropriately address needs cost health social care services escalate individuals live without appropriate supports compassionate communities apply population health theory practice wherein citizens mobilized along health social care supports holistically address needs persons experiencing vulnerabilitiesaimthe purpose study evaluate implementation compassionate community intervention vulnerable persons windsor ontario canadamethodsthis applied qualitative study informed consolidated framework implementation research collected analyzed focus group interview data 16 program stakeholders eight program clients three program coordinators two case managers regional health authority one administrator partnering community program two nursing student volunteers march june 2018 iterative analytic process applied understand aspects program work whyresultsthe findings suggest program acts safety net supports people falling cracks formal care system little things often biggest impact client wellbeing care delivery big little things achieved three key processes taking time advocating services resources empowering clients set personal health goals make authentic community connectionsconclusioncompassionate communities can address holistic personalized clientcentred needs people experiencing homelessness low income social isolation volunteers often untapped health social care capital can mobilized promote health vulnerable persons student volunteers may benefit experiencing responding needs communitys vulnerable members,0.0
altered brain functional network dynamics classic trigeminal neuralgia restingstate functional magnetic resonance imaging study background accumulating studies indicated wide range brain alterations respect structure function classic trigeminal neuralgia ctn given dynamic nature pain experience exploration temporal fluctuations interregional activity covariance may enhance understanding pain processes brain present study aimed characterize temporal features functional connectivity fc states well topological alteration ctnmethodsrestingstate functional magnetic resonance imaging threedimensional t1weighted images obtained 41 ctn patients 43 matched healthy controls hcs group independent component analysis sliding window based dynamic functional network connectivity dfnc analysis applied investigate specific fc states related temporal properties dynamics whole brain topological organization estimated calculating coefficient variation graphtheoretical properties correlation analyses performed measurements clinical dataresultstwo distinct states identified state 2 characterized complicated coupling default mode network dmn cognitive control network cc tight connections within dmn expressed ctn patients presented increased fractional windows dwell time moreover patients switched less frequently states hcs regarding dynamic topological analysis disruptions global graphtheoretical properties including network efficiency smallworldness observed patients coupled decreased variability nodal efficiency anterior cingulate cortex acc salience network sn thalamus caudate nucleus subcortical network sc variation topological properties showed negative correlation disease duration attack frequencyconclusionsthe present study indicated disrupted flexibility brain topological organization persistent noxious stimulation highlighted important role dynamic pain connectome regions including dmn cc sn pathophysiology ctn temporal fluctuation aspect additionally findings provided supplementary evidence current knowledge aberrant corticalsubcortical interaction pain development,0.0
explore correlation cerebral vessel characteristics cognitive impairment among elder individuals community study china background brain magnetic resonance imaging mri examination cerebral small vessel disease csvd may help screen vascular cognitive impairment recently estimated csvd score system suggested capture overall csvd burden study aimed detect association systemic evaluation score cerebral vascular imaging parameters cognitive functionsmethodsthis crosssectional study community settings october 2017 september 2018 elder 60 residents recruited onsite visit 6 communities shanghai china participants underwent brain mri carotid ultrasound laboratory tests blood urine samples cognitive function evaluated using minimental state examination mmse mri score csvd calculated according 2012 standard evaluation statistical changes imagingresultstotal 171 subjects completed survey examinations 55 participants diagnosed cognitive impairment total percentage 322 participants without cognitive impairment showed significant differences age bmi education level cognitive impaired participant disease history comorbidity hypertension chronic renal insufficiency higher level creatinine well lower level full blood count fbc alanine aminotransferase alt significant difference detected csvd score participants without cognitive impairment results linear regression analysis showed significant negative correlations mmse score left right carotid artery peak systolic velocity psv however csvd score borderline p 00566 positively correlated mmse multivariate linear correlation analysis including collected risk factor data showed left carotid artery psv score among independent negative correlated factors mmse multivariate binary logistic analysis showed age education history hypertension statistically associated factors cognitive impairmentconclusionsthe current study identified high prevalence cognitive impairment chinese community addition correlations cerebral vascular disease imaging status cognitive functions confirmed although sample size limited possibility screening cognitive impairment imaging technique,0.0
efficacy antifibrotic drugs nintedanib pirfenidone treatment progressive pulmonary fibrosis idiopathic pulmonary fibrosis ipf nonipf systematic review metaanalysis background research questions compare efficacy nintedanib pirfenidone treatment progressive pulmonary fibrosis compare efficacy antifibrotic therapy grouping nintedanib pirfenidone together patients ipf versus patients progressive lung fibrosis classified ipf study design methodsa search databases including medline embase pubmed clinicaltrialsgov conducted studies included randomised controlled trials pirfenidone nintedanib adult patients ipf nonipf patients extractable data mortality decline forced vital capacity fvc random effects metaanalyses performed changes fvc possible mortality selected studiesresults13 trials antifibrotic therapy pooled metaanalysis pirfenidone nintedanib considered together antifibrotic therapy change fvc expressed standardised difference allow pooling percentage absolute changes mean effect size ipf studies 0305 se 0043 p 0001 nonipf studies figures 0307 se 0063 p 0001 evidence difference two groups standardised rate fvc decline p 0979 pooling ipf nonipf showed significant reduction mortality mean risk ratio 0701 favour antifibrotic therapy p 0008 separate analysis restricted nonipf show significant reduction mortality risk ratio 0908 0547 1508 p 071interpretationantifibrotic therapy offers protection rate decline fvc progressive lung fibrosis similar efficacy shown two antifibrotic agents currently clinical use significant difference efficacy antifibrotic therapy whether underlying condition ipf nonipf progressive fibrosis supporting hypothesis common pathogenesis data analysis insufficient confident reduction mortality nonipf antifibrotic therapy trial registration prospero registration number crd42021266046,0.0
mood study protocol randomised controlled trial a2 betacasein versus conventional dairy products women low mood background betacasein major protein cows milk a1 a2 frequent variants recent evidence implicates a1 betacasein consumption mechanisms potential importance mental health yet possible effects psychological endpoints remains unknown primary aim study evaluate comparative effects consumption dairy products containing a2 betacasein versus conventional dairy ie containing a1 a2 betacasein symptoms psychological distress women low moodmethodsthe mood study 16week superiority 11 parallel group tripleblinded randomised controlled trial ninety women low mood patient health questionnaire score 5 will randomised consume either a2 betacasein conventional dairy products primary outcome symptoms psychological distress will measured 21item depression anxiety stress scale secondary outcomes will include symptoms depression anxiety stress severity low mood cognition gut microbiota composition gut symptomatology markers immune function gut inflammation systemic metabolites endothelial integrity oxidative stress body composition perceived wellbeing sleep quality life resource use costeffectivenessdiscussionthis study will advance understanding possible impact milk proteins psychological distress women well elucidate mechanisms underpinning association given dairy products form substantial component traditional western diets implications findings likely clinical public health importancetrial registrationthe trial protocol prospectively registered australia new zealand clinical trials registry actrn12618002023235 registered 17 december 2018,0.0
metformin alleviates calcification aortic valve interstitial cells activating pi3k#x2f akt pathway ampk dependent way background calcific aortic valve disease cavd prevalent valvular disease worldwide however effective treatment delay prevent progression disease due poor understanding pathological mechanism many studies showed metformin exerted beneficial effects multiple cardiovascular diseases mediating multiple proteins ampk nfb akt study aims verify whether metformin can inhibit aortic calcification pi3k akt signaling pathwaymethodswe first analyzed four microarray datasets screen differentially expressed genes degs signaling pathways related cavd aortic valve samples used verify selected genes pathways immunohistochemistry ihc western blot wb assays aortic valve interstitial cells avics isolated noncalcific aortic valves cultured phosphate medium pm without metformin verify whether metformin can inhibit osteogenic differentiation calcification avics finally used inhibitors sirna targeting ampk nfb akt study mechanism metforminresultswe screened 227 degs nfb pi3k akt signaling pathways implicated pathological mechanism cavd ihc wb experiments showed decreased ampk akt increased bax calcific aortic valves pm treatment significantly reduced ampk pi3k akt signaling pathways promoted bax bcl2 ratio induced avics calcification metformin treatment ameliorated avics calcification apoptosis activating pi3k akt signaling pathway ampk activation nfb inhibition inhibit avics calcification induced pm treatment however ampk akt inhibition reversed protective effect metforminconclusionsthis study first time demonstrates metformin can inhibit avics vitro calcification activating pi3k akt signaling pathway suggests metformin may provide potential target treatment cavd pi3k akt signaling pathway emerges important regulatory axis pathological mechanism cavd,0.0
quantitative contrast enhanced dual energy ct predict avascular necrosis feasibility study proximal humerus fractures background avascular necrosis delayed complication proximal humerus fractures increases likelihood poor clinical outcomes ct scans routinely performed guide proximal humerus fracture management hypothesized iodine concentration postcontrast dual energy ct scans identifies subjects develop avascular necrosis ischemia due compromised blood flow materials methods55 patients proximal humerus fractures enrolled 2014 2017 underwent clinical radiographic contrast enhanced dual energy ct assessment iodine densities humeral head glenoid control measured ct subjects managed open reduction internal fixation conservatively nonsurgical followed two years radiographic evidence avascular necrosis arthroplasty subjects underwent histopathologic evaluation ischemia resected humeral head results17 55 subjects 309 treated conservatively 21 382 underwent open reduction internal fixation 17 55 309 underwent arthroplasty 38 subjects treated conservatively orif 20 526 completed 12 months follow 14 368 24 months follow 12 months follow two 20 subjects 10 24 months 3 14 subjects 214 developed avascular necrosis 12 months mean humerus glenoid iodine ratio 105 standard deviation 024 subjects avn compared 091 024 24 months subjects avascular necrosis mean humerus glenoid iodine concentration ratio 106 017 compared 0924 021 17 arthroplasty subjects 2 severe ischemia iodine ratio 108 030 5 focal ischemia ratio 100 036 8 ischemia ratio 083 008 conclusionsquantifying iodine using dual energy ct subjects proximal humerus fractures technically feasible preliminary data suggest higher humeral head iodine concentration may increase risk avascular necrosis however future studies must enroll follow enough subjects managed open reduction internal fixation conservatively two years provide statistically significant resultstrial registrations nct02170545 registered june 23 2014 clinicaltrialsgov,0.0
case podocytic infolding glomerulopathy sle literature review background podocytic infolding glomerulopathy pig rare pathological change characterized microspheres microtubular structures thickened glomerular basement membrane gbm dozen cases reported worldwide far present case pig systemic lupus erythematosuscase presentationa 61yearold chinese female diagnosed systemic lupus erythematosus clinical manifestations proteinuria pleural effusion seroperitoneum anemia leukopenia thrombocytopenia antinuclear antibody positive hypocomplementemia also benign ovarian tumor epsteinbarr virus infection renal biopsy immunofluorescent staining showed igm c3 granularly deposited along capillary wall instead typical full house features electron microscopy showed lots microspheres structures seen thickened gbmconclusionwe present case pig patient systemic lupus erythematosus mechanisms pig unknown may associated connective tissue disease podocyte injury,0.0
mesangial sclerosis patient type 1 diabetes following simultaneous pancreaskidney transplantation despite maintenance normoglycemia case report background simultaneous pancreaskidney transplantation considered curative treatment type 1 diabetes complicated endstage kidney disease report herein case mesangial sclerosis patient underwent successful kidneypancreas transplantation despite wellcontrolled glucose excellent pancreatic allograft functioncase presentationa 76yearold type 1 diabetic man underwent simultaneous pancreaskidney transplantation 19 years prior presented persistent nephrotic range proteinuria although creatinine baseline normal level hemoglobin a1c fasting glucose well controlled without use insulin oral antihyperglycemic agents serum lipase amylase within reference range evidence donorspecific antibodies kidney allograft biopsy performed evaluate proteinuria showed diffuse capillary loop thickening diffuse moderate severe mesangial sclerosis resembling diabetic nephropathyconclusionsthis case demonstrates case mesangial sclerosis resembling diabetic nephropathy patient good glucose control simultaneous pancreaskidney transplantation excellent pancreatic allograft function,0.0
epigenetics neurodegenerative disorders induced pesticides abstractneurodegenerative diseases becoming major socioeconomic burdens however still effective treatment growing evidence indicates excess exposure pesticides involved development various forms neurodegenerative neurological diseases trigger epigenetic changes inducing disruption epigenome review summaries studies epigenetics alterations nervous systems relation different kinds pesticides highlighting potential mechanism etiology precision prevention target therapy various neurodegenerative diseases addition current gaps research future areas study also discussed,0.0
dise#x2f 6mer seed toxicitya powerful anticancer mechanism implications diseases abstractmicro mi rnas short noncoding rnas seed sequence pos 27 8 guide strand regulate cell function targeting complementary sequences seed matches located mostly 3 untranslated region 3 utr mrnas short rna enters rna induced silencing complex risc can kill cells mirnalike rna interference 6mer seed sequence pos 27 guide strand grich nucleotide composition grich seeds mediate 6mer seed toxicity targeting crich seed matches 3 utr genes critical cell survival resulting death induced survival gene elimination dise predominantly affects cancer cells may contribute cell death disease contexts review summarizes recent findings role dise 6mer seed tox cancer therapeutic potential contribution therapy resistance selectivity normal cells protected addition explore connection 6mer seed toxicity aging relation cancer certain neurodegenerative diseases,0.0
autoimmunity longterm safety efficacy alemtuzumab multiple sclerosis benefit#x2f risk following review trial postmarketing data abstractdoes preexisting treatmentemergent autoimmunity increase risk subsequent autoimmune disease individuals relapsingremitting multiple sclerosis ms alemtuzumab extended phase 2 3 trials 34 96 354 patients 395 1120 353 without preexisting autoimmunity developed nonms autoimmunity thyroid autoimmunity alemtuzumab courses 1 2 increase subsequent nonthyroid autoimmune adverse events therefore autoimmune disease alemtuzumab treatment predict autoimmunity courses preclude adequate alemtuzumab dosing control ms finally postmarketing safety data contribute toward full record alemtuzumab benefit risk profile ms field,0.0
creating digital toolkit reduce fatigue promote quality life multiple sclerosis participatory design usability study jmir form res 2021 dec 9 5 12 e19230 doi 102196 19230abstractbackground fatigue one common debilitating symptoms multiple sclerosis ms experienced 80 people ms facets fatigue applying cognitive behavioral energy effectiveness techniques lifestyle evidencebased facetoface 6session group fatigue management program people ms homework tasks integral part facets currently undertaken paperbased form feedback consultation undertaken facets attendees health care professionals experience delivering facets program suggested able complete homework tasks digitally desirable potentially enhancing engagement adherence enabling onthego access fit busy lifestyles relative longterm conditions apps specifically ms available many developed little input people msobjective purpose mixed methods study create digital toolkit comprising homework tasks eg activity diary goal planner thought diary facets program people ms considering end users unique requirements throughout design build prototyping testing stagesmethods phase 1 involved elicitation detailed user requirements toolkit via 2 focus groups previous attendees facets n3 n6 wireframing phase 2 involved supervised usability testing people ms n11 iterative prototyping usability sessions involved going test scenarios using facets toolkit android test phone video capture concurrent thinkaloud followed completion system usability scale sus semistructured interview collecting feedback design content functionalityresults mean sus score digital toolkit 743 sd 168 95 ci 632856 range 37595 equates adjective rating good b grade 70th79th percentile range saurolewis curved grading scale number usability design issues simplifying overall screen flow better meet users needs suggestions improvements using locationbased services displaying personalized information progress via central dashboard addressed implemented usability testing cycleconclusions work highlights importance participation people ms across entire development cycle working humancentered design methodology enable considered mscentered solution developed continued horizon scanning emergent technological enhancements will enable us identify opportunities improvements facets toolkit prior launch toolkit supports selfmonitoring management fatigue potential applicability longterm conditions fatigue significant issuepmid34889744 doi102196 19230,0.0
evaluation pediatric rheumatology telehealth satisfaction covid19 pandemic background coronavirus disease 2019 pandemic ambulatory pediatric rheumatology healthcare rapidly transformed mainly telehealth model however pediatric patient caregiver satisfaction broadly deployed telehealth programs remains largely unknown study aimed evaluate patient caregiver satisfaction telehealth identify factors associated satisfaction generalizable sample pediatric rheumatology patientsmethodspatients initial telehealth video visit rheumatology provider april june 2020 eligible patients caregivers sent postvisit survey assess modified version telehealth usability questionnaire tuq demographic clinical characteristics tuq total subscale usefulness ease use effectiveness satisfaction scores calculated classified positive based responses agree strongly agree 5point likert scale results analyzed using standard descriptive statistics wilcoxon signed rank testing association demographic clinical characteristics tuq scores assessed using univariate linear regressionresults597 patients caregivers met inclusion criteria survey response rate 42 n 248 juvenile idiopathic arthritis common diagnosis 335 majority patients diagnosed greater 6 months previously 726 prescribed chronic medications 597 median total tuq score 4 iqr 45 positive responses 81 items subscales usefulness scores lowest median 4 p 0001 telehealth saves time traveling highest median item score median 5 iqr 45 within subscales items scored significantly lower included convenience providing needs seeing rheumatologist well person acceptable way receive rheumatology services p 0001 significant demographic clinical features associated tuq scoresconclusionsour results suggest telehealth promising mode healthcare delivery pediatric rheumatic diseases also identifies opportunities improvement innovation research needed design telehealth system delivers high quality safe care improves healthcare outcomes since telehealth rapidly emerging form pediatric rheumatology care improved engagement training patients caregivers providers may help improve patient experience future,0.0
behavioral aspects nurse practitioners associated optimal multiple sclerosis care spain plos one 2021 dec 8 16 12 e0261050 doi 101371 journalpone0261050 ecollection 2021abstractbackground nurse practitioners nps play critical role multidisciplinary management patients multiple sclerosis ms neurologists behavioral characteristics associated suboptimal clinical decisions however limited information available impact among nps involved ms care aim study assess nurses therapeutic choices understand behavioral factors influencing decision making processmethods noninterventional crosssectional webbased study conducted nps actively involved care patients ms invited participate study spanish society neurology nursing participants answered questions regarding standard practice therapeutic management seven simulated relapsingremitting ms rrms case scenarios behavioral battery used measure participants life satisfaction mood positive social behaviors feeling helpfulness attitudes toward adoption evidencebased innovations occupational burnout healthcarerelated regret outcome interest therapeutic inertia ti defined lack treatment escalation clinical radiological evidence disease activity score quantify ti created based number simulated scenarios treatment intensification warrantedresults overall 331 nps invited participate 130 initiated study 96 29 completed study mean age sd 446 98 years 917 female seventythree participants 760 felt opinions significant influence neurologists therapeutic decisions sixteen nps 165 showed severe emotional exhaustion related work 13 135 depressive symptoms mean sd ti score 097 11 fiftysix nps showed ti least one case scenario higher years nursing experience p 0014 feeling helpfulness p 0014 positive attitudes toward innovations p 0046 higher intensity carerelated regret p 0021 associated lower risk ti adjusted r2 028 burnout associated higher risk ti p 0001 conclusions although nps prescribe ms treatments spain behavioral characteristics may influence management patients rrms continuing education specific strategies reducing occupational burnout may lead better management skills improve ms carepmid34879095 doi101371 journalpone0261050,0.0
osteopontin levels associated latetime lower regional brain volumes multiple sclerosis sci rep 2021 dec 8 11 1 23604 doi 101038 s41598021031733abstractosteopontin opn proinflammatory marker produced systemic immune central nervous system cns resident cells examined level opn cerebrospinal fluid csf blood associated latetime regional brain volumes white matter wm lesion load ms concentrations opn blood csf related mri findings 101 20 years later 46 patients ms opn concentration measured elisa regional brain volumes lesion load assessed magnetic resonance imaging mri using 3d mprage sequence automated mr volumetry opn measured csf associated several regional brain volumes wm lesion load measured 101 20 years later csf opn concentration correlated longterm enlargement lateral inferior lateral ventricles elevation gross csf volume conjunction reduction several cortical subcortical gray matter wm volumes serum opn showed longterm association regional brain volumes opn measured csf serum associated lower regional brain volumes measured decade later indicating primary role inflammation within cns developing longterm brain related alterationspmid34880402 doi101038 s41598021031733,0.0
identifying temporal electrophysiological molecular changes contribute tscassociated epileptogenesis jci insight 2021 dec 8 6 23 e150120 doi 101172 jciinsight150120abstracttuberous sclerosis complex tsc caused heterozygous mutations tsc1 tsc2 frequently results intractable epilepsy made use inducible tsc1knockout mouse model allowing us study electrophysiological molecular changes tsc1induced epileptogenesis time recorded pyramidal neurons hippocampus somatosensory cortex l2 l3 combined analysis transcriptome changes epileptogenesis deletion tsc1 resulted hippocampusspecific changes excitability adaptation emerged seizure onset progressed time phenotypes rescued early treatment rapamycin mtor inhibitor later epileptogenesis observed hippocampal increase excitationtoinhibition ratio cellular changes accompanied dramatic transcriptional changes especially seizure onset changes rescued upon rapamycin treatment genes encoding ion channels belonging gene ontology term action potential 27 differentially expressed just seizure onset suggesting potential driving role epileptogenesis data highlight complex changes driving epileptogenesis tsc including changed expression multiple ion channels study emphasizes inhibition tsc mtor signaling pathway promising therapeutic approach target epilepsy patients tscpmid34877936 doi101172 jciinsight150120,0.0
can improve experiences patients families request medical assistance dying multicentre qualitative study background medical assistance dying available canada 5 years unclear practices contribute highquality care aimed describe patient family perspectives quality care medical assistance dyingmethodswe conducted multicentre qualitative descriptive study including face face virtual onehour interviews using semistructured guide interviewed 21 englishspeaking patients found eligible medical assistance dying 17 family members four sites canada november 2017 september 2019 interviews deidentified analyzed iterative process thematic analysisresultswe identified 18 themes sixteen themes related single step process medical assistance dying maid requests maid assessments preparation dying death aftercare two themes coordination patientcentred care theme consistently across multiple steps maid process themes alongside participant recommendations developed clinical practice suggestions can guide careconclusionspatients families identified processspecific successes challenges process medical assistance dying importantly identified need care coordination patientcentred approach central highquality care research required characterize aspects care influence patient family satisfaction,0.0
elevated resting heart rate associated increased radiographic severity knee hand joints sci rep 2021 dec 8 11 1 23697 doi 101038 s41598021032374abstractalthough resting heart rate rhr predicts clinical outcomes cardiovascular disease chronic obstructive lung disease diabetes mellitus risk cancer role patients musculoskeletal diseases osteoarthritis oa remains unclear explored association rhr extents radiographic changes knees hands 2369 subjects donggu study radiographic hand knee joint findings graded semiquantitatively calculated total hand knee joint scores multiple linear regression performed examine associations rhr radiographic characteristics joints knee joints rhr associated positively total p 001 osteophyte p 001 joint space narrowing jsn p 001 tibial attrition p 002 scores adjustment age sex body mass index smoking status alcohol consumption educational physical activity levels comorbidities hand joints rhr associated positively jsn p 001 subchondral cyst p 001 scores adjustment rhr associated total osteophyte sclerosis erosion malalignment score hand joints study first reveal association rhr radiographic severity knee hand oapmid34880392 doi101038 s41598021032374,0.0
identifying comorbidities lifestyle factors contributing cognitive profile early parkinsons disease background identifying modifiable risk factors cognitive impairment early stages parkinsons disease pd estimating impact cognitive status may help prevent dementia pdd design cognitive trialsmethodsusing standard approach assessment global cognition pd controlling effects age education disease duration explored associations cognitive status comorbidities metabolic variables lifestyle variables 533 pd participants coppadis studyresultsamong overall sample 21 participants classified pdmci n 114 4 pdd n 26 prevalence hypertension diabetes dyslipidemia significantly higher cognitively impaired patients betweengroup differences found smoking alcohol intake use supplementary vitamins better cognitive scores significantly associated regular physical exercise p 005 cognitive stimulation 001 cognitive performance negatively associated interleukin 2 il2 p 005 il6 p 005 iron p 005 homocysteine p 0005 levels positively associated vitamin b12 levels p 0005 conclusionswe extend previous findings regarding positive negative influence various comorbidities lifestyle factors cognitive status early pd patients reinforce need identify treat potentially modifiable variables intention exploring possible improvement global cognitive status patients pd,0.0
cterminal ataxin2 disordered region promotes huntingtin protein aggregation neurodegeneration drosophila models huntington#39 s disease g3 bethesda 2021 oct 9jkab355 doi 101093 g3journal jkab355 online ahead printabstractthe ataxin2 atx2 protein contributes progression neurodegenerative phenotypes animal models amyotrophic lateral sclerosis als type 2 spinocerebellar ataxia sca2 parkinsons disease huntingtons disease hd however atx2 protein contains multiple separable activities deeper understanding requires experiments address exact mechanisms atx2 modulates neurodegeneration nd progression recent work two als models c9orf72 fus drosophila shown cterminal intrinsically disordered region cidr atx2 protein required assembly ribonucleoprotein rnp granules essential progression neurodegenerative phenotypes well accumulation protein inclusions associated als models show atx2cidr also similarly contributes progression degenerative phenotypes accumulation huntingtin protein aggregates drosophila models hd huntingtin established component rnp granules observations support recently hypothesized unexpected proteinhandling function rnp granules contribute progression huntingtons disease potentially proteinopathiespmid34718534 doi101093 g3journal jkab355,0.0
brighter spotty lesions spinal mri help differentiate aqp4 antibodypositive nmosd mogad abstractin large acute myelitis cohort aimed determine whether brighter spotty lesions bsls using refined terminologyon spinal magnetic resonance imaging mri help distinguish aquaporin4 antibodypositive neuromyelitis optica spectrum disorder aqp4nmosd myelin oligodendrocyte glycoprotein antibody disease mogad experienced neuroradiologist two neurologists independently analyzed 133 spinal mri scans 65 mogad 68 aqp4nmosd acquired within 1 month attacks bsls observed 18 61 30 participants aqp4nmosd none 49 participants mogad showed bsl p 0001 bsl acute phase useful differentiate aqp4nmosd mogad,1.0
expert opinion covid19 vaccination use cladribine tablets clinical practice ther adv neurol disord 2021 dec 7 1417562864211058298 doi 101177 17562864211058298 ecollection 2021abstractbackground gaps current evidence guidance leave clinicians unanswered questions use cladribine tablets treatment multiple sclerosis ms era covid19 pandemic particular relating covid19 vaccinationobjective describe consensusbased program led international ms experts aim supplementing current guidelines treatment labels providing timely recommendations relating covid19 vaccination use cladribine tablets clinical practicemethods steering committee sc 10 international ms experts identified 7 clinical questions answer concerning use cladribine tablets covid19 vaccination addressed issues relating patient selection timing efficacy safety clinical recommendations address question drafted using available evidence combined expert opinion sc extended faculty 28 ms experts representing 19 countries addition 10 sc members voted recommendations consensus recommendations achieved 75 respondents expressed agreement score 79 9point scaleresults consensus achieved 13 recommendations clinical recommendations provided whether patients ms receiving cladribine tablets vaccinated covid19 whether prioritized timing vaccination around dosing cladribine tablets ie treatment course safety covid19 vaccination patientsconclusion expert recommendations provide timely guidance covid19 vaccination patients receiving cladribine tablets relevant everyday clinical practicepmid34899987 pmcpmc8655448 doi101177 17562864211058298,0.0
increasing power analysis responder endpoints rheumatology software tutorial background composite responder endpoints feature frequently rheumatology due multifaceted nature many conditions current analysis methods used analyse endpoints discard much data used classify patients responders therefore highly inefficient resulting low power highlight novel augmented methodology uses information available improve precision reported treatment effects since methods challenging implement developed free userfriendly software available webbased interface r packages software consists two programs one supports analysis responder endpoints second facilitates sample size estimation demonstrate use software conduct analysis augmented standard analysis method using muse study phase iib trial patients systemic lupus erythematosusresultsthe software outputs similar point estimates smaller confidence intervals odds ratio risk ratio risk difference estimators using augmented approach sample size required arm future trial using novel approach based muse data 50 versus 135 standard method translating reduction required sample size approximately 63conclusionswe encourage trialists use software demonstrated implement augmented methodology future studies improve efficiency,0.0
interleukin17 affects synaptic plasticity cognition experimental model multiple sclerosis cell rep 2021 dec 7 37 10 110094 doi 101016 jcelrep2021110094abstractcognitive impairment ci disabling concomitant multiple sclerosis ms complex controversial pathogenesis cytokine interleukin17a il17a involved immune pathogenesis ms possible effects synaptic function cognition still largely unexplored study show il17a receptor il17ra highly expressed hippocampal neurons ca1 area exposure il17a dosedependently disrupts hippocampal longterm potentiation ltp activation receptor p38 mitogenactivated protein kinase mapk experimental autoimmune encephalomyelitis eae il17a overexpression paralleled hippocampal ltp dysfunction vivo behavioral analysis shows visuospatial learning abilities preserved eae induced mice lacking il17a overall study suggests key role il17 axis neuroimmune crosstalk occurring hippocampal ca1 area potential involvement synaptic dysfunction msrelated cipmid34879272 doi101016 jcelrep2021110094,0.0
evaluating course completion appropriateness burden understanding multiple sclerosis massive open online course cohort study j med internet res 2021 dec 7 23 12 e21681 doi 102196 21681abstractbackground massive open online course mooc research emerging field date research area focused participant engagementobjective aim study evaluate participant engagement measures satisfaction appropriateness burden mooc entitled understanding multiple sclerosis ms among cohort 3518 international course participantsmethods assessed association key outcomes participant education level ms status caregiver status sex age using summary statistics 2tailed t tests chisquare testsresults 3518 study participants 928 2637 people living ms among 2590 participants living ms 862 3328 identified formal informal caregivers key findings follows course completion rate among study participants 6717 2363 3518 course well received 9697 1502 1549 participants satisfied appropriate pitch low burden mean 22 hours engagement per week people living ms less likely living ms complete course people recent diagnosis ms caregivers participants without university education likely apply material course completionconclusions understanding ms mooc fit purpose presents information way readily understood course participants applicable livespmid34878985 doi102196 21681,0.0
basal lamina changes neurodegenerative disorders background neurodegenerative disorders group ageassociated diseases characterized progressive degeneration structure function cns two key pathological features disorders bloodbrain barrier bbb breakdown protein aggregationmain bodythe bbb composed various cell types noncellular componentthe basal lamina bl although different cells affect bbb well studied roles bl bbb maintenance function remain largely unknown addition located perivascular space bl also speculated regulate protein clearance via meningeal lymphatic glymphatic system recent studies laboratory others shown bl actively regulates bbb integrity meningeal lymphatic glymphatic function physiological pathological conditions suggesting may play important role pathogenesis progression neurodegenerative disorders review focus changes bl major components aging neurodegenerative disorders including alzheimers disease ad parkinsons disease pd amyotrophic lateral sclerosis als first introduce vascular lymphatic systems cns next discuss bl major components homeostatic conditions summarize changes aging ad pd als rodents humans functional significance alterations potential therapeutic targets also reviewed finally key challenges field future directions discussedconclusionsunderstanding bl changes functional significance changes neurodegenerative disorders will fill gap knowledge field goal provide clear concise review complex relationship bl neurodegenerative disorders stimulate new hypotheses research field,0.0
multiple sclerosis international federation guideline methodology offlabel treatments multiple sclerosis mult scler j exp transl clin 2021 dec 7 7 4 20552173211051855 doi 101177 20552173211051855 ecollection 2021 octabstractbackground total 28 million people living multiple sclerosis due disparities access medicines ability treat condition varies widely offlabel diseasemodifying therapies sometimes available affordable different health systems appropriate methodology integral creating highquality trustworthy guidelines article outline multiple sclerosis international federations msif approach creating guidelines offlabel treatments multiple sclerosismethods use guidelines international network gin mcmaster guideline development checklist grading recommendations assessment development evaluations grade evidencetodecision etd framework developed detailed health descriptors health outcomes panel drafted pico population intervention comparator outcome questions prioritised outcomes collaborate independent organisations systematically review collate information actively engaging stakeholders consulting relevant organisations boards working groups individualsresults draft guideline recommendations will published open comment stakeholders will encouraged endorse disseminate guidelines methodology ensures integrity transparency criteria evidence judgement used make recommendationsconclusions approach will facilitate transparent creation highquality trustworthy guidelines allow global guidelines adopted adapted national settingspmid34900327 pmcpmc8655455 doi101177 20552173211051855,0.0
cd8+ cell somatic mutations multiple sclerosis patients controlsenrichment mutations stat3 genes implicated hematological malignancies plos one 2021 dec 7 16 12 e0261002 doi 101371 journalpone0261002 ecollection 2021abstractsomatic mutations central role cancer role diseases common autoimmune disorders clear previously others demonstrated especially cd8+ t cells blood can harbor persistent somatic mutations patients multiple sclerosis ms rheumatoid arthritis concentrated cd8+ cells detail tested commonly somatic mutations detectable ii overall mutation load differ ms patients controls iii somatic mutations accumulate nonrandomly certain genes separated peripheral blood cd8+ cells newly diagnosed relapsing ms patients n 21 well matched controls n 21 performed nextgeneration sequencing cd8+ cells dna limiting search custom panel 2524 immunity cancer related genes enabled us obtain median sequencing depth 2000x discovered nonsynonymous somatic mutations ms patients controls cd8+ cell dna samples significant difference number groups p 060 median allelic fraction 05 range 0286 mutations showed statistically significant clustering especially stat3 gene also enrichment smarca2 dnmt3a socs1 ppp3ca genes known activating stat3 mutations found ms patients controls overall 1 5 mutations previously described cancer mutations detected clustering suggests selection advantage mutated cd8+ clones calls research possible phenotypic effectspmid34874980 doi101371 journalpone0261002,0.0
clinical characteristics surgical outcomes isolated inferior rectus palsy abstractaimas isolated inferior rectus muscle irm palsy represents rare clinical entity limited information available condition aim report elucidate etiology clinical characteristics surgical outcomes isolated irm palsymethodsisolated irm palsy cases underwent surgical treatments zhongshan ophthalmic center sun yatsen university china period january 2008 june 2019 reviewed retrospectively data evaluated cases included etiology ocular alignment ocular motility surgical procedures surgical outcomesresultsa total 61 patients 40 males 21 females included review mean sd age 2721 1603 years range 2 73 years cases 32 525 involved traumatic injury 28 459 congenital hypoplasia absence inferior rectus 1 16 thyroid ophthalmopathy right eye affected 33 patients 541 left 24 patients 393 eyes 4 patients 66 main clinical presentations consisted hypertropia affected eye motility limitation abduction depression incyclotropia treatment consisting various surgical approaches including muscle repair resection affected inferior rectus recession ipsilateral superior rectus elongation contralateral superior oblique partial transposition horizontal rectus isolated irm palsy rectified 49 patients 804 one surgery 11 cases 180 required two surgeries 1 case 16 needed three surgeries finally 52 patients 852 showed complete recovery 6 99 improved 3 49 experienced surgical failureconclusionthe main etiologies isolated irm palsy involved traumatic injury developmental events overall surgical outcomes various approaches employed quite effective,0.0
structural mri profiles tau correlates atrophy autopsyconfirmed cte background chronic traumatic encephalopathy cte neurodegenerative tauopathy currently diagnosed life atrophy patterns magnetic resonance imaging effective vivo biomarker cte characterized mechanisms neurodegeneration cte unknown characterized macrostructural magnetic resonance imaging features brain donors autopsyconfirmed cte association hyperphosphorylated tau ptau atrophy magnetic resonance imaging examinedmethodsmagnetic resonance imaging scans obtained medical record requests 55 deceased symptomatic men autopsyconfirmed cte 31 men n 11 deceased normal cognition time scan 60 years three neuroradiologists visually rated regional atrophy microvascular disease 0 none 4 severe microbleeds cavum septum pellucidum presence neuropathologists rated tau severity atrophy autopsy using semiquantitative scalesresultscompared unimpaired males donors cte 45 55stage iii iv greater atrophy orbitalfrontal mean diff129 dorsolateral frontal mean diff131 superior frontal mean diff105 anterior temporal mean diff157 medial temporal lobes mean diff160 larger lateral mean diff172 third mean diff080 ventricles controlling age scan ps005 effects posterior atrophy microvascular disease donors cte increased odds cavum septum pellucidum 67 p 005 among donors cte greater tau severity across 14 regions corresponded greater atrophy magnetic resonance imaging beta 068 p 001 conclusionsthese findings support frontaltemporal atrophy magnetic resonance imaging finding cte show ptau accumulation associated atrophy cte,0.0
virtual hand illusion younger older adults j rehabil assist technol eng 2021 dec 7 820556683211059389 doi 101177 20556683211059389 ecollection 2021 jandecabstractintroduction embodiment involves experiencing ownership body localizing space informed multiple senses visual proprioceptive tactile evidence suggests embodiment multisensory integration may change older age virtual hand illusion vhi used investigate multisensory contributions embodiment never evaluated older adults spatiotemporal factors unique virtual environments may differentially affect embodied perceptions older younger adultsmethods twentyone younger 1835 years 19 older 65+ years adults completed vhi paradigm body localization measured baseline subjective ownership ratings following synchronous asynchronous visualtactile interactionsresults higher ownership ratings observed synchronous relative asynchronous condition effects localization drift found age differences observed localization accuracy biased age groups virtual hand aligned real hand indicating visual mislocalization virtual handconclusions agerelated differences vhi observed mislocalization hand vr occurred groups even congruent aligned however tactile feedback reduced localization biases results expand current understanding agerelated changes multisensory embodiment within virtual environmentspmid34900329 pmcpmc8655451 doi101177 20556683211059389,0.0
trapeziectomy basal thumb osteoarthritis increase risk developing wrist osteoarthritis long term background symptomatic osteoarthritis basal joint thumb trapeziometacarpal joint common disabling condition mainly affecting women frequently treated complete removal trapezium without softtissue interposition limited evidence whether removal trapezium affects stability wrist joint increases risk developing wrist osteoarthritis aim study evaluate longterm prevalence oa wrists previous trapeziectomy compared wrists intact trapeziummethodspatients treated surgery trapeziometacarpal osteoarthritis one orthopedic department invited 1029 mean 17 years postoperatively bilateral radiographic examination included radiographs 114 hands trapeziectomy 46 hands intact trapezium 38 patients unilateral trapeziectomy intact contralateral trapezium radiographs blinded intact trapezium trapezial space trapeziectomy visible radiographs evaluated radiocarpal midcarpal osteoarthritis independently two assessors using three different osteoarthritis grading systems including kellgrenlawrence classification patients rated satisfaction function hands visual analog scale vas 0 100 higher score better resultsthe prevalence osteoarthritis ranged 20 26 mostly mild kellgrenlawrence grade 1 prevalence osteoarthritis differ wrists previous trapeziectomy intact trapezium whole cohort subgroup patients unilateral trapeziectomy intact contralateral trapezium significant difference hand function vas scores hands previous trapeziectomy hands intact trapezium whole cohort subgroupconclusionsremoval trapezium treatment basal thumb osteoarthritis increase risk developing wrist osteoarthritis long term,0.0
cascade process mediated left hippocampus left superior frontal gyrus affects relationship aging cognitive dysfunction background cognitive function declines age shown associated atrophy brain regions including prefrontal cortex however details relationship aging cognitive dysfunction well understoodmethodsacross wide range ages 24 85yearsold research measured gray matter volume structural magnetic resonance imaging data 39 participants brain regions set mediator variables assess cascade process aging cognitive dysfunction path analysisresultspath analysis showed age affected left hippocampus thereby directly affecting left superior frontal gyrus furthermore gyrus directly affected higher order flexibility maintenance abilities calculated wisconsin card sorting test two abilities affected assessment general cognitive functionconclusionour finding suggests cascade process mediated left hippocampus left superior frontal gyrus involved relationship aging cognitive dysfunction,0.0
association body mass index adolescence young adulthood longterm risk multiple sclerosis populationbased study neurology 2021 oct 25101212 wnl0000000000012957 doi 101212 wnl0000000000012957 online ahead printabstractobjective prospectively investigate longterm relationship body mass index bmi adolescents young adults risk multiple sclerosis ms population levelmethods utilized data populationbased compulsory norwegian tuberculosis screening program 19631975 including objectively measured height weight approximately 85 eligible citizens combined data norwegian ms registry biobank november 2020 bmi standardized according age sex risk ms calculated using cox proportional hazard modelsresults 30 829 506 years followup found 1 409 cases ms among 648 734 participants eligible age groups 1434 years overall obesity associated increased ms risk hr 153 95 ci 125188 risk similar men hr 14 95 ci 095206 women hr 159 95 ci 125202 risk highest youngest age groups age 1416 hr 173 95 ci 119253 1719 hr 161 95 ci 108239 2024 hr 156 95 ci 104236 longer present older 30 yearsconclusion high bmi individuals aged 14 24 years associated increased msrisk later life males femalespmid34697245 doi101212 wnl0000000000012957,0.0
high bmi youths modifiable risk factor multiple sclerosis weighing evidence neurology 2021 oct 25101212 wnl0000000000012966 doi 101212 wnl0000000000012966 online ahead printno abstractpmid34697244 doi101212 wnl0000000000012966,0.0
clinical relevance glomerular igm deposition patients lupus nephritis background aim study investigate clinical relevance igm deposition patients lupus nephritis ln large cohortresults217 patients renal biopsyproven active ln enrolled associations glomerular igm deposition clinicopathological parameters analyzed igm deposition positively correlated glomerular c1q c3 deposition moderately r 0436 p 0001 r 0408 p 0001 respectively inversely correlated plasma levels c3 cfh mildly r 0138 p 0043 r 0147 p 0037 respectively multivariate analysis found glomerular igm deposition independently contributed glomerular c3 deposition patients ln 2002 95 ci 12953094 p 0002 addition also found patients igm 02+ similar plasma cfh levels patients igm3+4+ plasma cfh levels significantly lower 3004 1558 g ml vs 4299 1875 g ml p 0001 furthermore patients high density glomerular igm low levels cfh heavier proteinuria higher serum creatinine lower plasma c3 levels 57 31 g d vs 47 35 g d p 0037 1501 1210 mol l vs 1056 971 mol l p 0005 03 02 g l vs 04 02 g l p 004 respectively comparing low density glomerular igm low levels cfh conclusionsour results suggested involvement glomerular deposited igm complement activation renal injury ln,0.0
selfadministered gerocognitive examination longitudinal cohort testing early detection dementia conversion background significant cognitive changes individuals age identified timely manner delaying diagnosis treatments use brief multidomain selfadministered objective cognitive assessment tools may remove barriers assessing identifying cognitive changes compared longitudinal selfadministered gerocognitive examination sage test scores nonselfadministered minimental state examination mmse scores 5 different diagnostic subgroupsmethodsa cohort study evaluating annual rates change performed 665 consecutive patients ohio state university memory disorders clinic patients least two visits 6 months apart evaluated sage mmse classified according standard clinical criteria subjective cognitive decline scd mild cognitive impairment mci alzheimers disease ad dementia included pattern change sage scores compared mmse one way repeated measures anova linear regression models usedresultsfour hundred twentyfour individuals 40 scd 94 mci nonconverters dementia 70 mci converters dementia 49 ad dementia 21 nonad dementia 220 ad dementia met inclusion criteria sage mmse scores declined respectively annual rates 191 points year p 00001 168 points year p 00001 mci converters ad dementia 182 points year p 00001 238 points year p 00001 ad dementia subjects sage mmse scores remained stable scd mci nonconverters statistically significant decline baseline scores sage occurred least 6 months earlier mmse mci converters ad dementia 144 vs 204 months mci converters nonad dementia 144 vs 329 months ad dementia individuals 83 vs 144 months conclusionssage detects mci conversion dementia least 6 months sooner mmse selfadministered sage also addresses critical need removing barriers performing cognitive assessments limitations singlesite cohort study include potential referral sampling biases repetitively administering sage identifying stability decline may provide clinicians objective cognitive biomarker impacting evaluation management choices,0.0
regional heterogeneity astrocyte morphogenesis dictated formin protein daam2 modifies circuit function embo rep 2021 oct 11e53200 doi 1015252 embr202153200 online ahead printabstractastrocytes display extraordinary morphological complexity essential support brain circuit development function formin proteins key regulators cytoskeleton however role astrocyte morphogenesis across diverse brain regions neural circuits unknown show loss formin protein daam2 astrocytes increases morphological complexity cortex olfactory bulb elicits opposing effects astrocytic calcium dynamics differential physiological effects result increased excitatory synaptic activity cortex increased inhibitory synaptic activity olfactory bulb leading altered olfactory behaviors proteomic profiling immunoprecipitation experiments identify slc4a4 binding partner daam2 cortex combined deletion daam2 slc4a4 restores morphological alterations seen daam2 mutants results reveal new mechanisms regulating astrocyte morphology show congruent changes astrocyte morphology can differentially influence circuit functionpmid34633730 doi1015252 embr202153200,0.0
proximal distal effects genetic susceptibility multiple sclerosis t cell epigenome nat commun 2021 dec 6 12 1 7078 doi 101038 s4146702127427wabstractidentifying effects genetic variation epigenome diseaserelevant cell types can help advance understanding first molecular contributions genetic susceptibility disease onset establish genomewide map dna methylation quantitative trait loci cd4+ tcells isolated multiple sclerosis patients utilizing map colocalization analysis identify 19 loci haplotype drives multiple sclerosis susceptibility local dna methylation also identify two distant methylation effects multiple sclerosis susceptibility loci chromosome 16 locus affects prdm8 methylation chromosome 4 region previously associated multiple sclerosis aggregate effect multiple sclerosisassociated variants major histocompatibility complex influences dna methylation near prkca chromosome 17 overall present new resource key cell type inflammatory disease research uncover new gene targets study predisposition multiple sclerosispmid34873174 doi101038 s4146702127427w,0.0
immunomodulatory peptide dendrimer inspired glatiramer acetate angew chem int ed engl 2021 oct 7 doi 101002 anie202113562 online ahead printabstractglatiramer acetate ga random polypeptide drug used treat multiple sclerosis ms chronic autoimmune disease aim identifying precisely defined alternative ga synthesized library peptide dendrimers amino acid composition similar ga challenged dendrimers trigger release antiinflammatory cytokine interleukin1 receptor antagonist il1ra human monocytes one effects ga immune cells several largest dendrimers tested active ga detailed profiling best hit showed dendrimer induces differentiation monocytes towards m2 antiinflammatory state ga however distinct immune marker profile peptide dendrimer might serve starting point develop welldefined immunomodulatory analog gapmid34618395 doi101002 anie202113562,0.0
csf neurofilament light chain predicts 10year clinical radiologic worsening multiple sclerosis mult scler j exp transl clin 2021 dec 6 7 4 20552173211060337 doi 101177 20552173211060337 ecollection 2021 octabstractbackground neurofilament light chain nfl attractive biomarker disease activity progression ms lack longterm prognostic dataobjective test longterm clinical radiological prognostic value cerebrospinal fluid csf nfl among newly diagnosed patients msmethods newly diagnosed ms patients followed prospectively baseline csfnfl repeated mri clinical assessments 10 years associations baseline csfnfl longitudinal mri clinical assessments found generalized estimating equations analysisresults fortytwo participants included csfnfl baseline significantly associated rate atrophy globus pallidus p 0009 hippocampus p 0001 evaluated mri baseline volumes thalamus 033 95 ci 057 010 p 0006 t1 028 95 ci 011 044 p 0001 t2 016 95 ci 004 027 p 0008 lesions baseline levels csfnfl 09 95 ci 03 15 p 0002 significantly predicted edss worsening 10 years baseline csfnfl gave comparable prediction best mri volumetric predictorsconclusion csfnfl predicted clinical radiological course newly diagnosed patients ms 10year period underlining prognostic rolepmid34900328 pmcpmc8652913 doi101177 20552173211060337,0.0
stress signal ulbp4 nkg2d ligand upregulated multiple sclerosis shapes cd8 + tcell behaviors neurol neuroimmunol neuroinflamm 2021 dec 6 9 1 e1119 doi 101212 nxi0000000000001119 print 2022 janabstractbackground objectives posit involvement natural killer group 2d nkg2d pathway multiple sclerosis ms pathology via presence specific nkg2d ligands nkg2dls aim evaluate expression nkg2dls cns csf patients ms identify cellular stressors inducing expression ul16binding protein 4 ulbp4 detectable nkg2dl finally evaluate impact ulbp4 functions cytokine production motility cd8+ t lymphocytes subset largely expressing nkg2d cognate receptormethods human postmortem brain samples csf patients ms controls used evaluate nkg2dl expression vitro assays using primary cultures human astrocytes neurons performed identify stressors inducing ulbp4 expression human cd8+ t lymphocytes ms donors age sexmatched healthy controls isolated evaluate functional impact soluble ulbp4results detected mrna coding 8 identified human nkg2dls brain samples patients ms controls ulbp4 protein expression detectable western blot ulbp4 levels greater patients ms particularly active chronic active lesions normalappearing white matter compared normalappearing gray matter ms donors white gray matter controls soluble ulbp4 also detected csf patients ms controls smaller shed soluble form 25 kda significantly elevated csf female patients ms compared controls male patients ms data indicate soluble ulbp4 affects various functions cd8+ t lymphocytes first enhanced production proinflammatory cytokines gmcsf interferon ifn second increased cd8+ t lymphocyte motility favored kinapselike behavior cultured presence human astrocytes cd8+ t lymphocytes patients ms especially altered presence soluble ulbp4 compared healthy controlsdiscussion study provides new evidence involvement nkg2d ligand ulbp4 ms pathology results point ulbp4 viable target specifically block 1 component nkg2d pathway without altering immune surveillance involving nkg2dlpmid34873031 doi101212 nxi0000000000001119,0.0
neuroimaging predictors longitudinal disability cognition outcomes multiple sclerosis patients systematic review metaanalysis abstractbackground crosssectional magnetic resonance imaging mri studies generated substantial evidence relating neuroimaging abnormalities clinical cognitive decline multiple sclerosis ms longitudinal neuroimaging studies may additional value predicting future cognitive deficits clinical impairment potentially leading earlier interventions better disease management conducted metaanalysis longitudinal studies using neuroimaging predict cognitive decline ie symbol digits modalities test sdmt disability outcomes ie expanded disability status scale edss msmethods systematic literature search yielded 64 relevant publications encompassing 105 distinct subanalyses performed multilevel randomeffects metaanalysis estimate overall effect size neuroimagingnulls ability predict longitudinal cognitive clinical decline metaregression investigate impact distinct study factors pooled effect sizeresults edss analyses metaanalysis yielded medium overall pooled effect size pearsonnulls correlation coefficient r042 95 ci 037 046 metaregression indicated analyses exclusively evaluating gray matter tissue significantly stronger effect sizes analyses white matter tissue whole brain analyses p005 study factors significantly influenced pooled effect size p005 sdmt analyses metaanalysis yielded medium overall pooled effect size r047 95 ci 032 060 metaregression found significant study factors influencing pooled effect sizeconclusion present findings indicate brain imaging medium predictor longitudinal change disability progression edss cognitive decline sdmt findings reinforce need longitudinal studies standardizing methods using multimodal approaches creating data consortiums publishing complete datasets investigating mri modalities predict longitudinal disability cognitive decline,0.0
single cell sequencing analysis identifies geneticsmodulated ormdl3+ cholangiocytes higher metabolic effects primary biliary cholangitis background primary biliary cholangitis pbc classical autoimmune disease highly influenced genetic determinants many genomewide association studies gwas reported numerous genetic loci significantly associated pbc susceptibility however effects genetic determinants liver cells immune microenvironment pbc remain unclearresultswe constructed powerful computational framework integrate gwas summary statistics scrnaseq data uncover geneticsmodulated liver cell subpopulations pbc based multiomics integrative analysis 29 risk genes including ormdl3 gsnk2b ddah2 significantly associated pbc susceptibility combining gwas summary statistics scrnaseq data found cholangiocytes exhibited notable enrichment pbcrelated genetic association signals permuted p 005 risk gene ormdl3 showed highest expression proportion cholangiocytes liver cells 2238 ormdl3+ cholangiocytes prominently higher metabolism activity score ormdl3 cholangiocytes p 138 1015 compared ormdl3 cholangiocytes 77 significantly differentially expressed genes among ormdl3+ cholangiocytes fdr 005 significant genes associated autoimmune diseasesrelated functional terms pathways ormdl3+ cholangiocytes exhibited relatively high communications macrophage monocyte compared ormdl3 cholangiocytes vegf signaling pathway specific ormdl3+ cholangiocytes interact cell populationsconclusionsto best knowledge first study integrate genetic information single cell sequencing data parsing geneticsinfluenced liver cells pbc risk identified ormdl3+ cholangiocytes higher metabolism activity play important immunemodulatory roles etiology pbcgraphical abstract,0.0
patientcentred evaluation phantom skin wetness sensory symptom people multiple sclerosis abstractbackground noticeable unknown proportion people multiple sclerosis pwms report sudden experience wetness dry skin site ie phantom wetness yet lack patientcentred investigations prevalence subjective experience uncomfortable symptomobjectives assess prevalence phantom wetness pwms association individual factors subjective experiencemethods 757 pwms completed online survey assessing frequency subjective experience phantom wetness calculated descriptive statistics odd ratios performed thematic analysis extract patientcentred description phantom wetnessresults 220 participants reported experiencing phantom wetness 29 females affected relapsing remitting rr ms 217 139 334 p0001 173 123 240 p0001 times likely experience phantom wetness males affected rr ms respectively thematic analysis indicated phantom wetness often experienced water trickling skin lower limbconclusion phantom wetness paraesthesia occurring almost third sample surveyed clinicians encouraged discuss pwms validate experience genuine symptom using patientgenerated language report may help facilitate conversations,0.0
optic nerve demyelination igg4 antineurofascin 155 antibodypositive combined central peripheral demyelination syndrome j cent nerv syst dis 2021 dec 6 1311795735211039913 doi 101177 11795735211039913 ecollection 2021abstractoptic nerve demyelination one clinical features combined central peripheral demyelination ccpd entity heterogenous immunopathogenesis clinical characteristics overlapping multiple sclerosis ms chronic inflammatory demyelinating polyneuropathy cidp interest earlier studies among patients cidp prior discovery antibodies paranodal protein neurofascin 155 antinf 155 also reported optic nerve dysfunction aimed evaluate optic nerve demyelination among antinf 155 cidp patients studied 2 patients antinf 155 cidp using visualevoked potentials vep optical coherence tomography oct patients distal acquired demyelinating symmetric dads subtype cidp common features prominent sensory ataxia hand tremors significantly elevated cerebral spinal fluid protein high titre antinf 155 antibodies poor response corticosteroid intravenous immunoglobulin ivig central nervous system neuroradiological abnormality detected normal visual acuity colour vision one subclinical right relative afferent pupillary defect rapd vep showed bilateral prolonged p100 latencies oct patient rapd demonstrated moderate severe retinal nerve fibre layer rnfl thinning identification optic nerve demyelination among subclinical cidp antinf 155 antibodies expanded spectrum demyelination within subset ccpdpmid34899003 pmcpmc8655830 doi101177 11795735211039913,1.0
antineuron antibody syndrome clinical features cytokines#x2f chemokines predictors background neuroimmunology rapidly expanding field recent discoveries new antibodies neurological syndromes current clinical studies focused disorders involving one specific antibody summarized class antibodies target common neuronal epitopes proposed term antineuron antibody syndrome anas study aimed clarify clinical range analyse clinical features cytokines chemokines predictors anasmethodsthis retrospective cohort study investigating patients neurological manifestations positive antineuron antibodiesresultsa total 110 patients identified 43 patients classified autoimmune encephalitis ae 67 classified paraneoplastic neurological syndrome pns regards antineuron antibodies 42 patients tested positive antinmethyldaspartate receptor nmdar antibody 19 antihu 14 antiyo 12 antipnma2 ma2 significant differences anas control groups serum b cellactivating factor baff levels cerebrospinal fluid csf cxc motif chemokine10 cxcl10 cxcl13 interleukin10 il10 baff transforming growth factor 1 tgf1 levels predictors poor outcomes included tumours p 00193 chronic onset p 00306 predictors relapses included lower levels csf baff p 00491 larger ratio serum tgf1 serum cxcl13 p 00182 conclusionsmost patients anas relatively good prognosis tumours chronic onset associated poor outcomes csf baff ratio serum tgf1 serum cxcl13 associated relapses,0.0
blood lactate concentrations rest exercise people multiple sclerosis systematic review metaanalysis abstractbackgroundmultiple sclerosis ms chronic disorder irreversibly damages axons within brain matter blood lactate concentration biomarker ms onset progression systematic review yet sought confirm dispute elevation biomarker potential blood lactate people ms pwms consolidate understanding lactate production exercise pwmsobjectiveto perform systematic review metaanalysis blood lactate pwms rest exertion compared healthy controls hc following chronic exercise interventionmethodsa systematic search six electronic databases pubmed cinahl science direct cochrane library sportdiscus pedro performed 10th april 2020 mean standard deviation sample size lactate measures rest exercise pooled determine overall effect size using random effects model 20point appraisal tool crosssectional studies utilised assess study quality inherent risk bias qualify inclusion studies include human adults 18 years confirmed clinical diagnosis ms published english undergone peer review report absolute blood lactate values data extraction involving testing exercise bilateral exercise methodsresults18 studies qualitatively analysed 15 studies quantitatively analysed outcome data available 1986 participants nms1129 total 7 papers tested blood lactate rest lactaterest 7 papers tested submaximal intensity exercise lactatesubmax 8 papers tested maximal intensity exercise lactatemax meta analyses showed elevated lactaterest reduced lactatemax pwms compared hc higher lactatemax lower edssscoring pwms compared higher edssscoring pwms lactatesubmax decreases lactatemax increases pwms following chronic exercise intervention qualitative analysis reported lactaterest reduced pwms following chronic exercise interventionconclusionslactaterest elevated pwms compared hc lactatemax lower pwms compared hc lower still higher compared lower edssscoring groups pwms chronic exercise interventions potential reduce lacatatesubmax given power output increase lactatemax pwms compared baseline values lactaterest may reduced pwms following chronic exercise intervention research required confirmation results review limited small sample sizes number studies available testing condition limited data available potentially confounding correlating factors eg vo2 power output well heterogeneity methodology adopted across studies often due lactate testing secondary outcome measureplslactate levels blood different rest intense exercise levels people multiple sclerosis ms compared healthy counterparts people ms showing smaller jump lactate intense exercise higher resting level exercising least 3 months blood lactate levels exercise may become similar levels seen people without multiple sclerosis research required give clearer picture can hopefully use blood lactate future measure progression ms individual well effectiveness exercise programme,0.0
covid19 vaccine intent appalachian patients multiple sclerosis abstractbackground rural people multiple sclerosis pwms face distinctive challenges covid19 pandemic purpose study determine covid19 vaccine intent factors associated vaccine hesitancy among appalachian adults msmethod conducted cross sectional phone inperson survey pwms large academic center west virginia wv february may 2021 study sample consists 306 adult participantsresults among 306 participants 104 3399 indicated vaccine hesitancy statistically significant factors p005 associated vaccine hesitancy compared received intend get vaccinated included concerns vaccine safety vaccine causing ms relapse vaccine making ms medication ineffective vaccine causing diseases getting covid19 infection vaccine fast approval vaccine ingredients well vaccine works sideeffects additional factors included prior bad experiences vaccines history getting flu vaccine lack consultation covid19 vaccine healthcare providersconclusions vaccine hesitancy among appalachian adult pwms higher compared pwms larger united states vaccine hesitancy especially higher among female younger 50 years old residing rural areas concerns vaccine safety perception infection risks past vaccine behaviors consultation healthcare providers important factors associated vaccine intent factors influencing vaccine hesitancy appalachian pwms largely consistent general public however concerns interaction vaccine ms specific population thus focus vaccine effort,0.0
fatigue associated physical inactivity people multiple sclerosis despite different environmental backgrounds merging comparing cohorts turkey israel abstractbackgroundexamining leisuretime physical activity people multiple sclerosis pwms different environmental backgrounds might increase understanding awareness inactivity pwms therefore study objective twofold compare level physical activity pwms israel turkey examine relationship level physical activity common diseaserelated symptoms demographical characteristics pwmsmethodscrosssectional data collected two centers combined physical activity level determined godin leisuretime exercise questionnaire subsequently classified one three subgroups active moderately active insufficiently active logistic regressions determined risks insufficiently active pwms according age gender body mass index disability impact walking impairment disease duration type ms perceived fatigue analysis variance test determined differences countries terms outcome variablesresultsthe study comprised 458 patients israel 575 turkey 682 turkish pwms classified insufficiently active compared 520 israeli pwms percentage insufficiently active pwms significantly higher categorized fatigued compared nonfatigued total cohort 724 vs 519 p0001 country separately based regression analysis fatigue main factor associated insufficiently physically active group odds ratio1968conclusionpwms increased fatigue tend participate less leisuretime physical activities compared nonfatigued observation supported merged data collected two countries turkey israel representing pwms different environmental backgrounds,0.0
impact mass vaccination sarscov2 infections among multiple sclerosis patients taking immunomodulatory diseasemodifying therapies england abstractbackgroundcontradicting assumptions made effectiveness sarscov2 vaccines patients multiple sclerosis ms receiving immunomodulatory diseasemodifying therapies dmts based quantification humoral cellular immune responses study aimed understand changes risk sarscov2 infection among total population patients receiving ms dmts england following mass vaccinationmethodsthis retrospective analysis national data collected prospectively longitudinally national health service nhs england nhs improvement nhse hold prescribing data commissioned ms dmts england united kingdom health security agency ukhsa collecting data registered sarscov2 test results including polymerase chain reaction rapid antigen tests patients receiving ms dmts identified using nhse datasets patients receiving ms dmts sarscov2 infection ie positive test march 2020 august 2021 identified merging nhse ukhsa datasets similar data general population captured using publicly available datasets united kingdom government incidence rate ratios irr sarscov2 infection among patients receiving ms dmts compared general population prevaccination november 2020 january 2021 postvaccination june august 2021 periods calculatedresultsa mean standard deviation 41 208 4 301 patients received ms dmt england month march 2020 august 2021 irr 95 confidence interval infection patients taking ocrelizumab versus general population increased 113 097131 prevaccination period 179 157203 postvaccination period patients fingolimod increased 087 073102 140 120163 periods significant changes patients ms dmtsconclusionsarscov2 vaccines offer less protection infection patients taking ocrelizumab fingolimod impaired immune response vaccines general population findings will implications vaccination policies,0.0
optogenetically controlled human functional motor endplate testing botulinum neurotoxins background lack physiologically relevant predictive cellbased assays one major obstacles testing developing botulinum neurotoxins bonts therapeutics humaninduced pluripotent stem cells hipscs derivatives now offer opportunity improve relevance cellular models thus translational value preclinical datamethodswe investigated potential hipscderived motor neurons hmns optical stimulation combined calcium imaging cocultured muscle cells activity investigate bontsensitivity vitro model human musclenerve systemresultsfunctional musclenerve coculture system developed using hmns human immortalized skeletal muscle cells results demonstrated hmns can innervate myotubes induce contractions calcium transient muscle cells generating vitro human motor endplate showing dosedependent sensitivity bonts intoxication implementation optogenetics combined live calcium imaging allows monitor impact bonts intoxication synaptic transmission human motor endplate modelconclusionsaltogether findings demonstrate promise optogenetically hipscderived controlled musclenerve system pharmaceutical bonts testing development,0.0
assessment automatic decisionsupport systems detecting active t2 lesions multiple sclerosis patients abstractbackgroundactive new enlarging t2 lesion counts routinely used clinical management multiple sclerosis thus automated tools able accurately identify active t2 lesions high interest neuroradiologists assisting clinical activityobjectiveto compare accuracy detecting active t2 lesions radiologically active patients based different visual automated methodsmethodsone hundred multiple sclerosis patients underwent two magnetic resonance imaging examinations within 12 months four approaches assessed detecting active t2 lesions 1 conventional neuroradiological reports 2 prospective visual analyses performed expert 3 automated unsupervised tool 4 supervised convolutional neural network gold standard reference outcome created consensus two observersresultsthe automated methods detected higher number active t2 lesions higher number active patients higher number falsepositive active patients visual methods convolutional neural network model sensitive detecting active t2 lesions active patients automated methodconclusionautomated convolutional neural network models show potential aid neuroradiological assessment clinical practice although visual supervision outcomes still required,0.0
emerging concepts treatment optic neuritis mesenchymal stem cellderived extracellular vesicles background optic neuritis frequently encountered multiple sclerosis neuromyelitis optica spectrum disorder antimyelin oligodendrocyte glycoprotein associated disease systemic autoimmune disorders hallmarks abnormal optic nerve inflammatory demyelination episodes optic neuritis tend recurrent particularly neuromyelitis optica spectrum disorder may result permanent vision lossmain bodymesenchymal stem cell msc therapy promising approach results remyelination neuroprotection axons demonstrated success clinical studies neurodegenerative diseases animal models however cell transplantation significant disadvantages complications cellfree approaches utilizing extracellular vesicles evs produced mscs exhibit antiinflammatory neuroprotective effects multiple animal models neurodegenerative diseases rodent models multiple sclerosis ms evs potential effective cellfree therapy optic neuritis antiinflammatory remyelination stimulating properties ability cross blood brain barrier ability safely administered without immunosuppressionconclusionwe review potential application msc evs emerging treatment strategy optic neuritis reviewing studies multiple sclerosis related disorders neurodegeneration discuss challenges potential rewards clinical translation evs including cell targeting carrying therapeutic micrornas prolonging delivery treatment optic neuritisgraphical abstract,1.0
exercise priming transcranial direct current stimulation study protocol randomized paralleldesign shamcontrolled trial mild cognitive impairment alzheimers disease background transcranial direct current stimulation tdcs noninvasive type brain stimulation uses electrical currents modulate neuronal activity small number studies investigated effects tdcs cognition patients mild cognitive impairment mci alzheimers disease ad demonstrated variable effects emerging evidence suggests tdcs effective applied active brain circuits aerobic exercise known increase cortical excitability improve brain network connectivity exercise may therefore effective yet previously unexplored primer tdcs improve cognition mci mild admethodsparticipants mci ad will randomized receive 10 sessions 2 weeks either exercise primed tdcs exercise primed sham tdcs tdcs alone blinded paralleldesign trial randomized exercise intervention will receive individualized 30min aerobic exercise prescriptions achieve moderateintensity dosage equivalent ventilatory anaerobic threshold determined cardiopulmonary assessment sufficiently increase cortical excitability tdcs protocol consists 20 min sessions 2 ma 5 times per week 2 weeks applied 35 cm2 bitemporal electrodes primary aim assess efficacy exercise primed tdcs improving global cognition using montreal cognitive assessment moca secondary aims evaluate efficacy exercise primed tdcs improving specific cognitive domains using various cognitive tests nback word recall word recognition tasks alzheimers disease assessment scalecognitive subscale neuropsychiatric symptoms neuropsychiatric inventory will also explore whether exercise primed tdcs associated increase markers neurogenesis oxidative stress angiogenesis changes markers correlated cognitive improvementdiscussionwe describe novel clinical trial investigate effects exercise priming tdcs patients mci mild ad proofofconcept study may identify previously unexplored noninvasive nonpharmacological combination intervention improves cognitive symptoms patients findings study may also identify potential mechanistic actions tdcs mci mild adtrial registrationclinicaltrialsgov nct03670615 registered september 13 2018,0.0
impact socioeconomic status mental health healthseeking behavior across race ethnicity large multiple sclerosis cohort abstractbackground psychiatric symptoms common multiple sclerosis ms may contribute worse ms outcomes previous studies suggest burden symptoms may vary race ethnicity socioeconomic status ses objective expand upon previous work explore associations ses race ethnicity predictors psychiatric symptoms mental health attitudes healthseeking behavior patients msmethods persons ms answered national webbased survey including demographic characteristics including race ethnicity measures ses mental health attitudes patient health questionnaire9 phq9 generalized anxiety disorder 7item gad7 scale modified fatigue impact scale 5item version mfis5 alcohol use disorders identification test audit survey also queried mental health availability perceptions care measured neighborhoodlevel ses nses participant using agency healthcare research quality ahrq index calculated 5digit postal codes indicators participantlevel ses included education level selfreported household income assessed association race ethnicity neighborhood participantlevel ses indicators affective symptom burden using generalized linear models adjusted age sex ms characteristicsresults 2095 participants answered survey mean ahrq index 54654 age 513122 years 7 black african american 54 hispanic latino 818 female lowest quartile nses disadvantaged likely either black african american hispanic latino compared highest quartile least disadvantaged lowest quartile nses higher mean mfis5 102 points 95 ci 039 143 phq9 124 points 95 ci 049 198 gad7 069 points 95 ci 001 138 scores relative highest quartile consumed alcohol n1489 participants lowest ahrq quartile lower mean audit scores 073 points 95 ci 118 029 compared higher quartiles race ethnicity associated selfreported psychiatric symptom burden cohort ses also associated selfreported improvement symptoms receiving mental health care higher proportion black african american 441 vs 302 p0003 hispanic latino 491 vs 306 p0001 participants likely report definitely go receive mental health care services colocated ms care compared white nonhispanic latino participants respectivelyconclusion higher ses associated lower burden psychiatric symptoms higher likelihood selfreported symptom recovery receiving mental health treatment attitudes regarding mental health care delivery ms varied according racial ethnic background future longitudinal studies diverse populations assess whether colocation mental health services ms care helps reduce gap access need mental health care ms,0.0
validation algorithms identifying outpatient infections ms patients using electronic medical records abstractbackground multiple sclerosis ms stakeholder groups expressed concerns whether ms diseasemodifying therapies dmts increase risk specific outpatient infections validated methods identifying risk selected outpatient infections general population either exist exclude clinically important possibility recurrent infections inaccurate largely existing studies relied primarily international classification diseases icd codes identify infectious outcomes additionally studies validated methods among ms population ms symptoms can mistaken infections eg urinary tract infections utis objective utilize multiple data elements electronic health record ehr improve accurate identification selected outpatient infections ms cohort general population controlsmethods searched kaiser permanente southern californianulls ehr based icd9 10 codes specified outpatient infections 1 1 200812 31 2018 among ms cohort n6000 51 general population controls matched age sex race ethnicity n30 010 random sample chart abstractions group used identify common coding errors outpatient pneumonia upper lower respiratory tract infection utis herpetic infections herpes zoster hz herpes simplex virus hsv fungal infections otitis media cellulitis influenza information used define discrete infectious episodes identify algorithm highest positive predictive value ppv supplementing icdcoded episodes radiology laboratory pharmacy dataresults ppvs relying icd codes alone inaccurate particularly identifying recurrent herpetic infections hz 42 hsv 60 utis 42 outpatient pneumonia 20 ms patients defining validating episodes improved ppvs selected infections final algorithmsnull ppvs 80100 ms 75100 general population including dispensed treatments uti herpetic infections yeast vaginitis timing dispensed treatments uti herpetic infections yeast vaginitis removal prophylactic antiviral use herpetic infections inclusion selected laboratory utis imaging results pneumonia exception outpatient pneumonia ppvs improved remained 70 significant differences ppvs final algorithms ms general populationconclusions provided herein accurate validated algorithms can used improve understanding risk recurrent outpatient infections influenced ms treatments msrelated disability comorbidities findings studies will important helping patients clinicians engage shared decisionmaking developing strategies mitigate risks recurrent infections,0.0
tunisian version brief international cognitive assessment multiple sclerosis validation normative values abstractbackground brief international cognitive assessment multiple sclerosis bicams specific batterie used identify cognitive impairment multiple sclerosis ms reliable easy way date arabicspeaking tunisian ms patients consensus use specific cognitive batteries msobjective aim work develop validate tunisian version bicams tbicams determine normative valuesmaterial methods patients diagnosed ms followed department neurology razi hospital recruited matched healthy controls according age sex educational level tbicams validity established comparing ms healthy controls symbol digit modalities test sdmt brief visual memory test bvmtr tunisian verbal learning tests tvlt used instead california verbal learning test cvltii results 104 ms patients 104 healthy controls comparable age sex educational level ms group exhibited lower performances tbicams domains compared healthy controls sdmt p0000 bvmtr p0002 tvlt p0000 tbicams cronbach alpha value 0741 normative values identified patients ms sdmt 3940 bvmtr 2627 tvlt 4344 cognitive impairment identified among 76 patients 731 males lower educational levels progressive ms associated severe cognitive impairmentconclusions current study established bicams valid reliable tool identification cognitive impairment tunisian ms population,0.0
epigenomewide association studies current knowledge strategies recommendations abstractthe aetiology pathophysiology complex diseases driven interaction genetic environmental factors variability risk outcomes diseases incompletely explained genetics environmental risk factors individually therefore researchers now exploring epigenome biological interface genetics environment can interact growing body evidence supporting role epigenetic mechanisms complex disease pathophysiology epigenomewide association studies ewases investigate association phenotype epigenetic variants commonly dna methylation decreasing cost measuring epigenomewide methylation increasing accessibility bioinformatic pipelines contributed rise ewases published recent years review current literature ewases provide recommendations strategies successfully conducting constrained review studies using methylation data studied epigenetic mechanism microarraybased data wholegenome bisulphite sequencing remains prohibitively expensive laboratories bloodbased studies due noninvasiveness peripheral blood collection availability archived dna well accessibility publicly available bloodcellbased methylation data address multiple novel areas ewas analysis covered previous reviews 1 longitudinal study designs 2 chip analysis methylation pipeline champ 3 differentially methylated region dmr identification paradigms 4 methylation quantitative trait loci methqtl analysis 5 methylation age analysis 6 identifying cellspecific differential methylation mixed cell data using statistical deconvolution,0.0
validation mri radiological reports pediatric ms according mcdonald 2017 criteria danish nationwide multicenter cohort study abstractbackgroundmri allows demonstration dissemination space time first demyelinating event however pediatric ms studies investigated validity msspecific outcomes described mri radiological reports clinicians rely make ms diagnosis assess ms treatment effect aim validate msspecific outcomes hospital mri reports pediatric ms comparing msspecific outcomes mri reports secondary mri reviewmethodsa senior consultant resident neurologist extracted data msspecific outcomes mri reports baseline followup children ms onset 200815 denmark gold standard expert neuroradiologists secondary mri review estimated percent agreement kappa values comparing data extracted hospital mri reports wanted test results secondary mri reviews gold standard resultsamong 55 children ms included 44 baseline 48 followup mris median age ms onset 163 years range 92179 agreement mri reports secondary mri review ranged 68100 msspecific outcomes agreement higher mri outcomes present kappa values ranged 042 moderate 100 excellent kappa fulfillment mcdonald 2017 criteria 060 baseline mri 053 followup mri kappa new lesion followup mri 041conclusionagreement moderate good msspecific outcomes ms neurologists data extraction hospital mri radiological reports compared neuroradiologists secondary mri review agreement moderate fulfilling mcdonald 2017 criteria acquiring new lesion followup mri recommend structured mri reporting children suspected acquired demyelinating syndromes increase validity hospital mri reports clinical use,1.0
cd19 b cell repopulation ocrelizumab alemtuzumab cladribine implications sarscov2 vaccinations multiple sclerosis abstractbackground ocrelizumab maintains bcell depletion via sixmonthly dosing whilst controls relapsing multiple sclerosis also inhibits seroconversion following sarscov2 vaccination unlike seen following alemtuzumab cladribine treatment emerging reports suggest 13 bcell repopulation facilitates seroconversion cd20depletionobjective determine frequency bcell repopulation levels ocrelizumab treatmentmethods relapse data lymphocyte cd19 bcell numbers obtained following requests clinical trial datarepositories information extracted phase ii ocrelizumab extension nct00676715 trial phase iii cladribine tablet nct00213135 alemtuzumab nct00530348 nct00548405 trials obtained clinical trial data requestsresults 35 people ms exhibit 1 bcells 6 months last infusion following 34 cycles ocrelizumab compared 5055 9 months 8590 12 months time relapses occurred consistent diseasebreakthrough rates compared people standard therapy contrast people 90100 exhibited 1 bcells treatment either cladribine alemtuzumabconclusions people demonstrate b cell repletion within 3 months last treatment alemtuzumab cladribine however people repopulate peripheral bcells standard ocrelizumab dosing controlled studies warranted examine view delaying dosing interval 36 months may allow people potentially seroconvert vaccination,0.0
effects adenovirusmediated knockdown irak4 synovitis osteoarthritis rabbit model background use interleukin1 receptorassociated kinase 4 irak4 inhibitor treatment inflammatory joint disease promising method however underlying mechanism osteoarthritis oa remains unclear purpose study look effects adenovirusmediated knockdown irak4 synovitis oa rabbit modelmethodsadshirak4 injected two weeks anterior cruciate ligament resection six weeks later rabbits killed expression irak4 tnfrassociated factor 6 traf6 tgfactivated kinase 1 tak1 pikb kinase pikk pnuclear factor kappab pnfb p38 pp38 synovial membrane detected western blot qrtpcr immunohistochemistry analysis immunohistochemistry detect expression irak4 proteins articular cartilage staining assess pathological changes synovium cartilage levels interleukin il 1 tumor necrosis factor tnf mmp13 synovial fluid measured elisa xray microcomputerized tomography ct scans used assess knee joint conditions microstructure subchondral boneresultsirak4 expression levels synovial tissues oa model group exhibited significant upward trend adshirak4 significantly reduced irak4 mrna expression synovium tissues notably adshirak4 suppressed tolllike receptor interleukin1 receptor tlr il1r signaling addition adshirak4 treatment group can see less inflammatory cell infiltration reduced hyperplasia angiogenesis levels il1 tnf mmp13 synovial fluid oa model group significantly higher control group reduced adshirak4 treatment finally results stains immunohistochemistry ct showed adshirak4 treatment protective effect cartilage damageconclusionsirak4 significantly upregulated synovium osteoarthritis rabbit model addition adshirak4 reduced expression irak4 suppressed tlr il1r signaling synovium osteoarthritis rabbit model adshirak4 alleviate synovitis cartilage degradation osteoarthritis rabbit model thus alleviate symptoms oa prevent progression oagraphical abstract,0.0
major sex differences migraine prevalence among occupational categories crosssectional study using uk biobank background migraine represents one prevalent neurological conditions worldwide disabling condition high impact working situation migraineurs interestingly genderrelated differences regarding association migraine important occupational characteristics hardly studiedmethodsthe current study scrutinizes genderspecific differences prevalence migraine across broad spectrum occupational categories shedding also light associations important jobrelated features shift work job satisfaction physical activity study included data 415 712 participants uk biobank cohort using official icd10 diagnosis migraine health conditions selection criteria prevalence ratios migraineurs compared healthy controls among different occupational categories jobrelated variables estimated using logbinomial regression analyses statistical models adjusted important sociodemographic features age bmi ethnicity education neuroticism better highlight specific differences men women stratified sexresultswe detected differential prevalence pattern migraine relation different job categories men women especially men migraine appears prevalent highly physically demanding occupations pr 138 95 ci 093 204 furthermore migraine also prevalent jobs frequently involve shift night shift work compared healthy controls interestingly prevalence especially high women shift work pr 145 95 ci 114 183 night shift work pr 146 95 ci 093 231 conclusionour results show migraine genderdependently associated physically demanding jobs shift working,0.0
prevalence multiple sclerosis clinical demographic characteristics kurdish populations western iran 2020 abstractbackground multiple sclerosis ms costly burdensome nervous system disorder leading several disabilities young middleaged people knowing ms clinical epidemiologic demographic characteristics may help estimate predict required health services medication facilities affected people study aimed determine prevalence ms demographic characteristic 2 million kurdish populations western iran 2020methods crosssectional study conducted 2020 ms patients kurdish ethnicity living kermanshah western iran mountainous area ms patients registered recruited study several centers settings approved nationwide ms registry iran nmsri using two questioners questionnaire included sex age age ms symptoms onset age diagnosis family history ms type ms second one expanded disability status scale edss checklist demographic information kermanshah province adopted statistical center iran addition descriptive statistics umannwhitney chisquare tests also usedresults total 1557 ms patients mean age sd 386699 years recruited study 1216 781 female majority patients 300 patients 193 age range 3539 years highest prevalence 18482 per 100000 populations observed age range 4044 years prevalence ms kermanshah province estimated 7950 per 100 000 people 12571 per 100 000 female 3441 per 100 000 male prevalence higher female female male 365 1 edss score significantly higher male female 30622 male versus 24218 female p0001 type ms significantly different male female spms ppms common male 31 103 22 73 female 81 75 39 36 p0012 positive family history ms found 126 patientsconclusion given information prevalence ms kermanshah 2012 prevalence ms kermanshah increased last decade ms disabilities extensive male rather female,0.0
maintained attention assessment patients affected myalgic encephalomyelitis#x2f chronic fatigue syndrome reliable biomarker abstractthe maintained attention cause great functional limitations cfs disease mainly affects women central period life cognitive function explored using montreal cognitive assessment maintained attention using toulousepiron test global index attention perception giap obtained fatigue using visual analog scale perception effort using modified borg scale final sample 84 patients 66 women 18 men met diagnostic criteria fukuda1994 carruthers2011 22 healthy controls 14 women 8 men patients maintain normal cognitive function showing low low attention score 70 patients marked cognitive fatigue compared control group p 005 significant differences genders giap fatigue cfs however sick women perceive cognitive effort higher men deficits sustained attention perception fatigue effort performing proposed test sensitive reliable indicator allows us substantiate clinical suspicion refer patients studies order confirm rule cfs,0.0
economic impact compassionate use medicines background compassionate use programs cup medicines respond ethical imperative providing access medicines marketing approval patients recruited trials economic impact clinical trials previously investigated evidence net economic benefit cup exists research aims address information gap estimating economic consequences 11 cup italy conducted march 2015 december 2020 perspective public health care system italy national health service eight programs concern cancer treatments two refer spinal muscular atrophy one indicated multiple sclerosismethodssince cup medicines covered industry net economic benefit includes avoided costs standard care soc patients received joined cup ii costs covered pharmaceutical industry sponsor instead sustained payers associated adverse events severe side effects resulting hospitalisation attributable cup medicines iii costs combination therapies diagnostic procedures used soc soc costing relied publicly available data information adverse events diagnostic procedures retrieved cup monetized using relevant fee episode service one cup excluded since soc identifiedresults2 713 patients treated 11 cup soc identified soc mean cost per patient ranged 11 415 20 299 total cost soc ranged 310 551 million mean cost per patient covered hospitals hosting cup equal 1 646 total cost 45 million net economic benefit ranged 265 million 506 millionconclusionsdespite research limitations paper illustrates first time net economic impact cup public payer perspective important integrate estimates prospective effects cup implementation ie economic value comparative benefit profile medicines used cup versus soc including effects societal perspective,0.0
progranulin potential therapeutic target immunemediated diseases j inflamm res 2021 dec 4 1465436556 doi 102147 jirs339254 ecollection 2021abstractprogranulin pgrn secretory glycoprotein consisting 593 amino acid residues key actor regulator multiple system functions innate immune response inflammation well tissue regeneration recently emerging evidence pgrn protective development variety immunemediated diseases including rheumatoid arthritis ra inflammatory bowel disease ibd type 1 diabetes mellitus t1dm multiple sclerosis ms regulating signaling pathways known critical immunology particularly tumor necrosis factor alpha tnf receptor tnf tnfr signaling pathway whereas role pgrn psoriasis systemic lupus erythematosus sle systemic sclerosis ssc controversial review summarizes immunological functions pgrn role pathogenesis several immunemediated diseases order provide new ideas developing therapeutic strategies diseasespmid34898994 pmcpmc8655512 doi102147 jirs339254,0.0
inhibition immunoproteasome lmp2 ameliorates ischemia#x2f hypoxiainduced bloodbrain barrier injury wnt#x2f catenin signalling pathway background disruption bloodbrain barrier bbb stroke can lead brain injury neurological impairment previous work confirmed involvement immunoproteasome subunit low molecular mass peptide 2 lmp2 pathophysiology ischemia stroke however relationship immunoproteasome lmp2 bbb remains unclearmethodsadult male spraguedawley rats subjected transient middle cerebral artery occlusion reperfusion mcao r three days mcao rats treated lentivirusmediated lmp2 shrna preparations stereotactical injection ipsilateral hemispheric region rat brain microvascular endothelial cell rbmvec line exposed oxygenglucose deprivation reperfusion ogd r mimic ischemic conditions vitro rna interferencemediated knockdown lmp2 catenin analysed vivo vitro analysis quantity extravasated evans blue eb cerebral fluorescent angiography performed evaluate integrity bbb immunofluorescence western blotting employed detect expression target proteins cell migration evaluated using scratch migration assay results immunofluorescence western blotting cell migration quantified using software imagej version 153m parametric data different groups compared using oneway anova followed least significant difference lsd testresultscerebral ischemia led lower levels structural components bbb tight junction proteins occludin claudin1 zo1 mcao r group compared sham group p 0001 however inhibition immunoproteasome lmp2 restored expression proteins resulting higher levels occludin claudin1 zo1 lmp2shrna group compared controlshrna group p 0001 addition inhibition immunoproteasome lmp2 contributed higher microvascular density decreased bbb permeability eg quantity extravasated eb lmp2shrna group 5854 737 g g vs controlshrna group 10374 432 g g p 0001 promoted upregulation wnt3a catenin proteins rats following mcao r vitro experiments ogd r induced marked upregulation lmp2 proapoptotic protein bax cleaved caspase3 downregulation occludin claudin1 zo1 bcl2 well inhibition wnt catenin pathway wnt3a catenin proteins rbmvecs compared control group normal culture conditions p 0001 however silencing lmp2 gene expression reversed protein changes promoted proliferation migration rbmvecs following ogd r silencing catenin transfection rbmvecs cateninsirna aggravated downregulation tight junction proteins reduced proliferation migration rbmvecs following ogd r compared controlsirna group p 0001 lmp2sirna cateninsirna cotransfection partly counteracted beneficial effects silencing lmp2sirna levels tight junction proteins rbmvecs exposed ogd rconclusionthis study suggests inhibition immunoproteasome lmp2 ameliorates ischemia hypoxiainduced bbb injury molecular mechanism involves immunoproteasomeregulated activation wnt catenin signalling pathway ischemic conditions,0.0
multidisciplinary approach drug gene delivery systems brain aaps pharmscitech 2021 dec 3 23 1 11 doi 101208 s12249021021441abstractdrug delivery brain long huge challenge bloodbrain barrier bbb offers great resistance entry foreign substances drugs inclusive brain barrier healthy individuals protective brain disallowing noxious substances present blood get brain allowing exchange small molecules brain diffusion however bbb disrupted certain disease conditions cerebrovascular diseases including acute ischemic stroke intracerebral hemorrhage neurodegenerative disorders including multiple sclerosis ms alzheimers disease ad parkinsons disease pd cancers review aims provide broad overview presentday strategies brain drug delivery emphasizing novel delivery systems hopefully review inspire scientists researchers field drug delivery across bbb uncover new techniques strategies optimize drug delivery brain considering anatomy physiology pathophysiological functioning bbb health disease conditions review focused controversies drawn conclusions recently published studies issues penetrability nanoparticles brain whether active targeted drug delivery brain achieved use nanoparticles also extended review cover novel nonnanoparticle strategies using viral peptide vectors noninvasive techniques enhance brain uptake drugspmid34862567 doi101208 s12249021021441,0.0
relationship balance confidence social engagement people multiple sclerosis abstractobjective evaluate relationships among patientreported balance confidence social satisfaction social participation people multiple sclerosis pwms methods 75 ambulatory pwms sustained least two falls near falls prior two months selfreported balance confidence activitiesspecific balance confidence abc questionnaire social satisfaction participation patient reported outcomes measurement information system promis measures correlations abc promis measures examined using spearmannulls rank correlationresults crosssectional analysis abc scores promis scores social satisfaction social participation statistically significantly correlated 037054 p 0001 correlation balance confidence social satisfaction consistently stronger time point balance confidence social participationconclusion selfreported balance confidence associated social satisfaction social participation pwms fall causal direction relationship remains uncertain,0.0
impact comorbid post traumatic stress disorder multiple sclerosis military veterans populationbased cohort study abstractbackgroundvery little known regarding impact post traumatic stress disorder ptsd course multiple sclerosis ms objectivesto explore impact preexisting ptsd ms relapses magnetic resonance imaging mri activity disability large populationbased cohortmethodsmilitary veterans ms ptsd prior symptom onset msptsd n96 identified using department veterans affairs ms databases msptsd cases matched ms controls without ptsd n95 number relapses number new t2 lesions new gadolinium lesions brain mri neurological disability abstracted 2015 2019resultsthe mean annualized relapse rate greater msptsd group versus controls 023 vs 006 respectively p005 annualized mean number new t2 gadoliniumenhancing lesions brain mri 052 vs 016 029 vs 008 respectively p005 disability accrual time disability status scale 60 rapid 237 vs 295years p005 relapsing ms patients ptsdconclusionpatients msptsd higher disease activity reach disability endpoints rapidly controls first study show ptsd potentially modifiable risk factor ms relapses mri activity disability,0.0
neurogenic bladder characteristics treatment approaches patients multiple sclerosis abstractobjectivesto analyze neurogenic bladder characteristics treatment approaches patients multiple sclerosis ms facilitate proper reasonable decisions relevant patientsdesignretrospective studysettingankara physical medicine rehabilitation training research hospital ankara turkeyparticipantsseventyfive patients ms included 20022015interventionurodynamic examinationoutcome measurethe detrusor type detrusor compliance sense bladder fullness storage disorder emptying disorder voided volume postvoid residual volume urine culture emptying method medical treatments recordedresultsthe study included 53 females 22 males mean age 36 101 years urodynamic examinations indicated 747 patients detrusor overactivity 747 detrusor hypocompliance 773 storage dysfunction 813 emptying dysfunction anticholinergic medication recommended 747 patients alphaadrenergic receptor blockers recommended 693 detrusor hypocompliance common group disease duration 10 years p0045 use external collector systems common urine culture frequently positive infections female patients p0001 p0049 respectively frequency normal bladderfilling sensation higher women p001 frequencies detrusor overactivity storage emptying disorders voided postvoid volumes ml bladder emptying methods different subgroups p005 conclusionthe study revealed significant neurogenic bladder dysfunction inadequate management dysfunction ms patients considering ms findings may progress time patients evaluated periodically controlling urinary system necessary modifications made treatments,0.0
investigating genetically mimicked effects statins via hmgcr inhibition immunerelated diseases men women using mendelian randomization sci rep 2021 dec 3 11 1 23416 doi 101038 s4159802102981xabstractstatins suggested potential treatment immunerelated diseases conversely statins might trigger autoimmune conditions clarify role statins allergic diseases autoimmune diseases conducted mendelian randomization mr study using established genetic instruments mimic statins via 3hydroxy3methylglutarylcoenzyme reductase hmgcr inhibition assessed effects statins asthma eczema allergic rhinitis rheumatoid arthritis ra psoriasis type 1 diabetes systemic lupus erythematosus sle multiple sclerosis ms crohns disease ulcerative colitis largest available genome wide association studies gwas genetically mimicked effects statins via hmgcr inhibition associated immunerelated diseases either study correcting multiple testing however positively associated risk asthma east asians odds ratio 205 per standard deviation sd decrease lowdensity lipoprotein cholesterol ldlc 95 confidence interval ci 120 352 p value 0009 associations differ sex robust sensitivity analysis findings suggested genetically mimicked effects statins via hmgcr inhibition little effect allergic diseases autoimmune diseases however exclude possibility genetically mimicked effects statins via hmgcr inhibition might increase risk asthma east asianspmid34862478 doi101038 s4159802102981x,0.0
white matter tracts overlap thalamus putamen protected multiple sclerosis pathology abstractbackgroundthe thalamus putamen highly connected hubs implicated multiple sclerosis ms pathology remains unclear white matter wm tracts pass different susceptibility ms pathology impact disability predominates exerted disease wm tracts hypothesized wm tracts connected passing hubs subsequently termed hub+ tracts susceptible msrelated pathology tracts pass hub tracts due retrograde anterograde distant degeneration thus compared lesion load neurite orientation dispersion density imaging noddi derived metrics hub+ hub tracts assessed relationship mri metrics physical impairmentmethodseighteen patients mean age 455 years 12 females 3 tesla mri consisting t1weighted t2weighted fluid attenuated inversion recovery flair noddi orientation dispersion index odi neurite density index ndi isotropic volume fraction ivf derived fortynine wm tracts ie 12 hub+ 37 hub tracts segmented exploratory analyses differences lesion burden whole tract normal appearing wm nawm noddi metrics carried two types tracts using mannwhitney u test correlations physical impairment assessed using expanded disability status scale edss timed 25foot walk t25fw assessed using spearman correlation analysesresultshub tracts larger t1 p0001 t2lesion p0001 volumes lower odi p0001 ndi p0001 higher ivf p0020 comparison hub+ tracts measures tissue injury hub+ tracts correlated clinical disability though less strongly hub tractsconclusionscontrary hypothesis exploratory pilot study results suggest wm tracts overlap thalamus putamen lower degree lesional nonlesional tissue injury suggesting protective role hubs ms pathology higher degree vulnerability passing hub stations also show weaker association disability impairment hub+ pathology compared hub tracts findings point potential role disease location relation hubs guidance treatment personalization ms,0.0
short review influence magnetic fields neurological diseases front biosci schol ed 2021 dec 3 13 2 181189 doi 1052586 s561abstractthis study reviews use magnetic electromagnetic fields emf pulsed electromagnetic fields pemf transcranial magnetic stimulation tms parkinsons disease alzheimers disease ad multiple sclerosis ms introduction provides review emf pemf tms based clinical observations followed description basic principles treatments literature review possible mechanisms describing coupling treatments biological responses response mechanisms include cell membrane embedded receptors channels pumps well signaling cascades within cell links cell organelles also discuss magnetic contribution coupling emf well recent finding cryptochrome putative magnetosensor conclusion summarizes complex network causal factors elicited emf arising cell membrane via signaling cascades radical oxygen species nitric oxide growth factors cryptochromes mechanisms involving epigenetic genetic changespmid34879470 doi1052586 s561,0.0
downregulating expression optn elevates neuroinflammation via aim2 inflammasome ripk1activating mechanisms app#x2f ps1 transgenic mice background neuroinflammation thought cause alzheimers disease ad partly caused inadequate mitophagy receptor mitophagy aimed reveal regulatory roles optineurin optn neuroinflammation pathogenesis admethodsbv2 cells app ps1 transgenic tg mice used vitro vivo experimental models determine regulatory roles optn neuroinflammation ad sophisticated molecular technologies including quantitative q rtpcr western blot enzyme linked immunosorbent assay elisa coimmunoprecipitation coip immunofluorescence employed reveal inherent mechanismsresultsas consequence key roles optn regulating neuroinflammation identified depressing activity absent melanoma 2 aim2 inflammasomes receptor interacting serine threonine kinase 1 ripk1 mediated nfb inflammatory mechanisms detail found expression optn downregulated resulted activation aim2 inflammasomes due deficiency mitophagy app ps1 tg mice ectopic expression optn blocks effects oligomer ao activating aim2 inflammasomes inhibiting mrna expression aim2 apoptosisassociated specklike protein containing cterminal caspase recruitment domain asc leading reduction active form caspase1 interleukin il 1 microglial cells moreover ripk1 also found negatively regulated optn via ubiquitin protease hydrolysis resulting synthesis il1 activating transcriptional activity nfb bv2 cells e3 ligase uban domain optn binds death domain dd ripk1 facilitate ubiquitination based observations ectopically expressed optn app ps1 tg mice deactivated microglial cells astrocytes via aim2 inflammasome ripkdependent nfb pathways leading reduce neuroinflammationconclusionsthese results suggest optn can alleviate neuroinflammation aim2 ripk1 pathways suggesting optn deficiency may potential factor leading occurrence ad,1.0
vitamin d supplementation systemic lupus erythematosus relationship disease activity fatigue interferon signature gene expression background addition wellknown role vitamin d calcium homeostasis bone metabolism vitamin d important modulation immune system inflammatory processes vitamin d deficiency common patients systemic lupus erythematosus sle possibly result sun avoidance aim prospective openlabel study assess effect treatment vitamin d deficiency insufficiency sle patients particularly regards disease activity fatigue interferon signature gene expressionmethods31 sle patients 13 vitamin d deficiency 18 vitamin d insufficiency treated vitamin d3 supplemented vitamin d3 8000 iu daily 8 weeks vitamin d deficient 8000 iu daily 4 weeks insufficient followed 2000 iu daily maintenance assessed baseline 6 12 months means interview filling questionnaires blood tests expression 12 interferon signature genes rna extracted whole blood measured using quantigene plex technologyresultsan improvement disease activity measured systemic lupus erythematosus disease activity index2k sledai2k p 0028 fatigue measured fatigue severity scale fss p 0071 12 months noted significant decrease antidouble stranded deoxyribonucleic acid dsdna titre p 0045 also noted mean interferon signature gene expression score decreased baseline 6 months however statistical significance achieved p 0165 conclusionsimproved disease activity fatigue noted vitamin d supplemented vitamin d deficient insufficient sle patients one possible mechanism suppression interferon signature gene expressiontrial registration study registered isrctn registry 12 04 2021 trial id isrctn59058825,0.0
vitamin d related genetic polymorphisms affect serological response highdose vitamin d supplementation multiple sclerosis plos one 2021 dec 2 16 12 e0261097 doi 101371 journalpone0261097 ecollection 2021abstractintroduction poor 25hydroxyvitamin d 25 oh d status much replicated risk factor developing multiple sclerosis ms several vitamin dassociated single nucleotide polymorphisms snps associated higher risk ms however studies benefit vitamin d supplementation ms show inconclusive results explore whether vitamin dassociated snps ms risk alleles confound serological response vitamin d supplementationmethods 34 participants solarium study consented genotyping 26 vitamin d data available solarium study randomised relapsingremitting ms patients placebo 14 000 iu vitamin d3 48 weeks participants categorised either carriers noncarriers risk allele 4 snps two related d binding protein dbp associated lower 25 oh d levels rs4588 rs7041 two related vitamin d metabolism enzymes cyp27b1 cyp24a1 associated higher risk ms rs12368653 rs2248359 respectively 25 oh d levels determined baseline 48 weeksresults dbprelated snps showed difference 25 oh d status baseline carriers rs7041 risk allele showed lower 25 oh dlevels compared noncarriers 48 weeks supplementation median 2242 vs 3320 nmol l p 0013 cyp related snps neither showed difference baseline carriers rs12368653 risk allele showed higher 25 oh dlevels compared noncarriers 48 weeks supplementation median 3041 vs 1520 nmol l p 0014 discussion vitamin drelated snps affect serological response highdose vitamin d supplementation effects common doses vitamin d well clinical consequence altered response need investigated furtherpmid34855907 doi101371 journalpone0261097,0.0
technical validation realworld monitoring gait multicentric observational study bmj open 2021 dec 2 11 12 e050785 doi 101136 bmjopen2021050785abstractintroduction existing mobility endpoints based functional performance physical assessments patient selfreporting often affected lack sensitivity limiting utility clinical practice wearable devices including inertial measurement units imus can overcome limitations quantifying digital mobility outcomes dmos supervised structured assessments realworld conditions validity imubased methods realworld however still limited patient populations rigorous validation procedures cover device metrological verification validation algorithms dmos computation specifically population interest daily life situations users perspective devicemethods analysis protocol designed establish technical validity patient acceptability approach used quantify digital mobility real world mobilised consortium funded european union eu part innovative medicine initiative aiming fostering regulatory approval clinical adoption dmosafter defining procedures metrological verification imubased device experimental procedures validation algorithms used calculate dmos presented include laboratory realworld assessment 120 participants five groups healthy older adults chronic obstructive pulmonary disease parkinsons disease multiple sclerosis proximal femoral fracture congestive heart failure dmos extracted monitoring device will compared different reference systems chosen according contexts observation questionnaires interviews will evaluate users perspective deployed technology relevance mobility assessmentethics dissemination study granted ethics approval centres committees londonbloomsbury research ethics committee helsinki committee tel aviv sourasky medical centre medical faculties university tbingen university kiel data algorithms will made publicly availabletrial registration number isrctn 12246987 pmid34857567 doi101136 bmjopen2021050785,0.0
results home mechanical ventilation national program among adults chile 2008 2017 background home mechanical ventilation hmv viable effective strategy patients chronic respiratory failure crf chilean ministry health started program adults 2008methodsthis study examined following data prospective cohort patients crf admitted national hmv program characteristics mode admission quality life time program survivalresultsa total 1105 patients included median age 59 years 4458 women accounted 581 sample average body mass index bmi 349 2646 kg m2 total 762 patients started hmv stable chronic mode 238 initiated hmv acute mode total 99 patients transferred childrens program 1047 patients noninvasive ventilation 58 patients invasive ventilation median baseline paco2 level 582 5265 mmhg device usage time 73 h d 5888 time hmv 216 122495 months diagnoses copd 35 obesity hypoventilation syndrome ohs 239 neuromuscular disease nmd 163 noncystic fibrosis bronchiectasis tuberculosis noncf bc tbc 83 scoliosis 59 amyotrophic lateral sclerosis als 524 baseline score severe respiratory insufficiency questionnaire sri 47 179 points significantly improved time lowest 1 3year survival rates observed als group lowest 9year survival rate observed noncf bc tb copd groups best survival rates 9 years ohs scoliosis nmd 2017 701 patients childrens program 722 adults program prevalence 104 per 100 000 inhabitantsconclusionthe common diagnoses copd ohs best survival observed patients ohs scoliosis nmd sri score improved significantly followup patients hmv prevalence hmv 104 per 100 000 inhabitantstrial registration study approved registered ethics committee north metropolitan health service santiago chile n 018 2021,0.0
charting global research strategy progressive msan international progressive ms alliance proposal backgroundprogressive forms multiple sclerosis ms affect 1 million individuals globally recent approvals ocrelizumab primary progressive ms siponimod active secondary progressive ms opened therapeutic door though results early trials neuroprotective agents mixed recent introduction term active secondary progressive ms therapeutic lexicon introduced potential confusion disease description thereby clinical managementobjectivethis paper reviews recent progress highlights continued knowledge proposes behalf international progressive ms alliance global research strategy progressive msmethodsliterature searches pubmed 2015 may 2021 conducted using search terms progressive multiple sclerosis primary progressive multiple sclerosis secondary progressive ms proposed strategies developed series inperson virtual meetings international progressive ms alliance scientific steering committeeresultssustaining accelerating progress will require greater understanding underlying mechanisms identification potential therapeutic targets biomarker discovery validation conduct clinical trials improved trial design encouraging developments symptomatic rehabilitative interventions starting address ongoing challenges experienced people progressive msconclusionwe need manage challenges realise opportunities context global research strategy will improve quality life people progressive ms,1.0
vaccination sarscov2 neuroinflammatory disease early safety#x2f tolerability data abstractbackground patients autoimmune disease immunotherapy largely excluded seminal vaccine trials led significant vaccine hesitancy patients neuroinflammatory diseases nid including limited multiple sclerosis ms neuromyelitis optica spectrum disorders nmosd neurosarcoidosis myelin oligodendrocyte antibodymediated disease mogad data urgently needed help guide clinical care nid populationmethods crosssectional observational study evaluating adults neurologistconfirmed diagnosis neuroinflammatory disease nid neurologically asymptomatic control population participants recruited multiple academic centers ms resilience covid19 collaborative study analyzed participant responses vaccinespecific questionnaire collected february may 2021results 1164 participants nid 595 controls completed vaccine survey hesitancy rates similar nid control groups n134 327 nid vs n56 306 control p082 common reasons hesitancy nid participants lack testing autoimmune population fear demyelinating neurologic event unvaccinated patients discussed vaccination doctor less likely hesitant n184 736 vs n83 597 p0007 634 nid patients 332 controls received least one dose vaccine sarscov2 time survey completion adjusting age bmi comorbidities difference selfreported side effects se groups first dose n256 422 nid vs 141 453 control p020 second dose n246 670 nid vs n114 648 control p085 mrna vaccines viralvector vaccines n6 46 nid vs n8 66 control p039 reported ses fell expected se profile difference report new recurrent neurologic symptoms n110 162 vaccinated vs 71 182 unvaccinated p044 radiologic disease activity n40 59 vaccinated vs n30 76 unvaccinated vaccinated unvaccinated nid participantsconclusions found difference patientreported vaccine side effects evidence nid worsening vaccination largescale realworld evidence needed validation,1.0
humoral immune response lymphocyte levels complete vaccination covid19 cohort multiple sclerosis patients treated cladribine tablets j cent nerv syst dis 2021 dec 2 1311795735211060118 doi 101177 11795735211060118 ecollection 2021abstractbackground patients multiple sclerosis ms receiving immunomodulatory drugs excluded clinical trials covid19 vaccines therefore data regarding efficacy covid19 vaccines induce humoral immunity ms patients treated b tcell depleting agents urgently warranted cladribine tablets highefficacy diseasemodifying treatment exerts therapeutic effect via sustained transient lymphocyte depletionaim report humoral responses german cohort ms patients treated cladribine tabletsmethods retrospective analysis included patients 18 years treated cladribine tablets relapsing ms first second year fully vaccinated covid19 two weeks second vaccination earliest blood samples obtained assessment antisarscov2 igg antibodies lymphocyte counts bcells cd4+ tcells cd8+ tcells antisarscov2 igg antibodies quantified liaison sarscov2 trimerics igg assay positivity defined cutoff value 338 bau mlresults total 38 patients 737 female aged 2366 years included analysis ten patients 263 treatmentnave initiating treatment cladribine tablets patients 842 received mrna vaccines time last dose cladribine tablets vaccination ranged 2 96 weeks six patients 158 vaccinated within 4 weeks last cladribine dose patients achieved positive antisarscov2 igg antibody levels humoral immune response independent age time vaccination relation last cladribine dose lymphocyte counts well b tcell countsconclusions treatment cladribine tablets impair humoral response covid19 vaccination time since last cladribine dose age prior therapy lymphocyte count well b tcell counts effect seropositivity antisarscov2 igg antibodiespmid34880703 pmcpmc8647228 doi101177 11795735211060118,0.0
25hydroxyvitamin d levels among 2yearold children findings japan environment childrens study jecs background study aim obtain epidemiological data vitamin d levels pediatric population japan assessed prevalence vitamin d deficiency insufficiency 2yearold japanese children using data large ongoing birth cohort studymethodsdata analysis obtained japan environment childrens study jecs subcohort study scs jecs evaluated childrens serum 25 oh d levels 5th 10th 25th 50th 75th 90th 95th percentiles rates vitamin d deficiency insufficiency also presented weighted prevalence rate vitamin d deficiency insufficiency among children jecsresultsafter excluding children missing 25 oh d2 25 oh d3 data analyzed 4655 remaining children 247 95 ci 235260 vitamin d deficiency 20 ng ml 513 95 ci 498527 risk vitamin d insufficiency 2030 ng ml estimated prevalence vitamin d deficiency insufficiency among children jecs 254 95 ci 241267 509 95 ci 494524 vitamin d deficiency found 229 boys 265 girls median serum 25 oh d concentrations lower among participants measured winter spring among measured summer autumn highest rate vitamin d deficiency observed hokkaido northernmost prefecture japanconclusionwe analyzed data serum 25 oh d levels birth cohort study found vitamin d deficiency insufficiency common among 2yearold japanese children sex season latitude affect serum 25 oh d concentrations,0.0
prevalence burden multiple sclerosisrelated fatigue systematic literature review background multiple sclerosis ms chronic demyelinating disease central nervous system results progressive irreversible disability fatigue one common msrelated symptoms characterized persistent lack energy impairs daily functioning burden msrelated fatigue complex multidimensional knowledge systematic literature review conducted subject purpose study conduct systematic literature review epidemiology burden fatigue people multiple sclerosis pwms methodssystematic searches conducted medline embase evidencebased medicine reviews identify relevant studies fatigue pwms englishlanguage records published 2010 january 2020 met predefined eligibility criteria included initially selected studies reported quality life qol economic outcomes according categories fatigue eg fatigued vs nonfatigued studies assessing associations economic outcomes fatigue continuous measure later included supplement available dataresultsthe search identified 8147 unique records 54 met inclusion criteria 39 reported epidemiological outcomes 11 reported qol 9 reported economic outcomes supplementary screen economic studies fatigue continuous measure included additional 20 recordsfatigue prevalence pwms ranged 365 780 msrelated fatigue consistently associated significantly lower qol results economic impact fatigue heterogeneous studies reported significant association presence severity fatigue employment status capacity work sick leave gap evidence regarding direct costs msrelated fatigue burden experienced caregivers pwmsconclusionfatigue prevalent symptom pwms associated considerable qol economic burden gaps evidence related direct costs msrelated fatigue burden fatigue caregivers addressing fatigue clinical course disease may improve health economic outcomes patients ms,1.0
implementation study 2021 german guideline diagnosis treatment multiple sclerosis highlightsfirst implementation study clinical practice guideline msearly aggressive treatment treatment stop major areas controversyoverall agreement survey datalow participation rates among neurologistsimproved implementation strategies needed,0.0
systemic inflammasome activation pyroptosis associate progression amnestic mild cognitive impairment alzheimers disease background growing evidence indicates inflammasomemediated inflammation plays important roles pathophysiology amnestic mild cognitive impairment amci alzheimers disease ad pyroptosis induced inflammasome gasdermin d gsdmd involved several neurodegenerative disorders however clear whether peripheral inflammasome pyroptosis activated amci ad patients influencing neuroinflammation aim study examine association systemic inflammasomeinduced pyroptosis clinical features amci admethodsa total 86 participants including 33 subjects amci 33 subjects ad 20 cognitively normal controls study mini mental state examination mmse montreal cognitive assessment moca scale used cognitive assessment levels inflammasomerelated genes proteins peripheral blood mononuclear cells pbmcs determined using quantitative polymerase chain reaction western blotting levels il1 a142 a140 ptau ttau cerebrospinal fluid csf well plasma il1 level measured enzymelinked immunosorbent assay finally lipopolysaccharides lps used investigate effects systemic inflammasomeinduced pyroptosis ad mice modelresultsseveral genes involved inflammatory response enriched pbmcs ad patients mrna protein levels nlrp3 caspase1 gsdmd il1 increased pbmcs amci ad patients il1 level plasma csf amci ad patients significantly higher controls negatively correlated csf a142 level well mmse moca scores furthermore positive correlation il1 level plasma csf amci ad patients vivo experiments showed systemic inflammasomeinduced pyroptosis aggravated neuroinflammation 5 fad miceconclusionsour findings showed canonical inflammasome signaling gsdmdinduced pyroptosis activated pbmcs amci ad patients addition proinflammatory cytokine il1 strongly associated pathophysiology amci ad targeting inflammasomeinduced pyroptosis may new approach inhibit neuroinflammation amci ad patients,0.0
experiences treatment multiple sclerosis natalizumab reallife cohort 15 years sci rep 2021 dec 2 11 1 23317 doi 101038 s41598021026656abstractnatalizumab ntz used treatment highly active relapsingremitting multiple sclerosis ms stopping ntz risk severe rebound phenomenon considered aimed investigate use ntz clinical routine focused identification potential risk factors disease reactivation treatment discontinuation medical university innsbruck austria identified ms patients treated ntz performed retrospective analysis therapeutic decision making disease course treatment ntz risk factors disease reactivation ntz discontinuation 235 ntz treated ms patients included 105 discontinued treatment ntz start disease duration 509 iqr 2091057 years average number total relapses 4 iqr 36 median edss 20 range 065 whereby values significantly decreased time reduction annualized relapse rate arr treatment 93 edss remained stable 64 multivariate regression models conversion secondary progressive ms spms treatment significantly associated lower risk disease reactivation ntz arr treatment associated earlier disease reactivation confirm high therapeutic efficacy ntz trends used earlier disease course nowadays discontinuation ntz seems safe patients convert spms treatment higher arr ntz increases risk disease reactivation treatment discontinuationpmid34857795 doi101038 s41598021026656,0.0
functional enrichment alternative splicing events nease reveals insights tissue identity diseases abstractalternative splicing important aspect gene regulation nevertheless role molecular processes pathobiology far understood roadblock tools functional analysis asset events lacking mitigate developed nease tool integrating pathways structural annotations proteinprotein interactions functionally characterize events show four application cases nease can identify pathways contributing tissue identity cell type development highlights splicingrelated biomarkers unique view nease generates unique meaningful biological insights complementary classical pathways analysis,0.0
valor pronstico del glutamato en el lquido cefalorraqudeo en esclerosis mltiple abstractthe objective study evaluate association glutamate glu levels cerebrospinal fluid csf disease onset disease progression follow cohort multiple sclerosis ms patients glu level measured disease onset first relapse mri obtained baseline followup every 12 months determine percent brain volume change pbvc cortical thickness ct t2 lesion volume t2lv primary predictors interest baseline csf glu levels pbvc ct well clinical disease progression measured expanded disability status scale edss annualized relapse rate followup total 26 ms patients included mean concentration glu csf diagnosis 53 04 m l significant association observed higher baseline levels glu increase edss follow b 106 95ci 047166 p 0003 well pbvc b 071 95ci 056138 p 0002 ct b 015 95ci 006033 p 001 observe association baseline glu levels relapse rate t2lv followup b 008 95ci 011043 p 011 b 195 95ci 39330 p 022 respectively higher glu concentrations disease onset associated increase pbvc edss progression followup ms patientskey words glutamate brain atrophy brain volume multiple sclerosis cerebrospinal fluid,0.0
systematic evaluation guidelines rehabilitation multiple sclerosis patients overview according icf functioning domains int j rehabil res 2021 oct 27 doi 101097 mrr0000000000000501 online ahead printabstracthighquality clinical practice guidelines cpgs can provide evidencebased recommendations optimizing care managing multiple sclerosis ms currently review compiles recommendations highquality cpgs guide decisionmaking ms rehabilitation aim identify evidencebased recommendations highquality multidisciplinary english cpgs rehabilitation ms cpgs published last 10 years 20092019 described recommendations rehabilitation searched pubmed turning research practice database international guideline databases national guideline databases websites ms organizations quality assessment cpgs conducted two evaluators using appraisal guidelines research evaluation ii instrument recommendations classified according international classification functioning disability health icf international classification health intervention ichi documented terms strength recommendation level evidence five cpgs satisfied inclusion criteria 120 recommendations 38 strong level moderate low level evidence 61 weak strength 18 formulated consensus experts recommendations categorized 12 domains 1 chapter body function level 1 chapter activity level 2 domains external factors existing cpgs demonstrated 100 evidence level recommendations followed clinical practice body functions icf developing uptodate cpgs focus activity participation domains countries various healthcare backgrounds may useful best clinical practicepmid34711756 doi101097 mrr0000000000000501,0.0
anca systemic sclerosis vasculitis overlaps vasculopathy devastating combination pathologies rheumatology oxford 2021 mar 21keab278 doi 101093 rheumatology keab278 online ahead printabstractin patients systemic sclerosis ssc coexistence ancaassociated vasculitis sscaav reported associated severe disease course including significant pulmonary renal involvement presence anca uncommon patients ssc therefore clinicians must maintain high index clinical suspicion sscaav panca antimpo antibodies common antibodies observed patients typically present clinical features microscopic polyangiitis renallimited vasculitis multiple areas potential interaction pathogenesis ssc aav can exacerbate compound vascular disease addition similar patterns major internal organ involvement eg lung kidneys seen conditions highlight diagnostic approach sscaav paucity data inform management sscaav typically treated per isolated aav can potentially hazardous patients ssc eg association highdose steroid scleroderma renal crisis propose rare clinical entity warrants rigorous investigation including definition therapeutic strategy ameliorate potentially devastating combination pathologies sscaavpmid33744916 doi101093 rheumatology keab278,0.0
etiological research pediatric multiple sclerosis tool assess environmental exposures pediatric italian genetic environment exposure questionnaire mult scler j exp transl clin 2021 dec 1 7 4 20552173211059048 doi 101177 20552173211059048 ecollection 2021 octabstractbackground etiology pediatriconset multiple sclerosis unknown although putative genetic environmental factors appear involved among children multiple sclerosis onset occurs closer susceptibility window thank adults exposure etiological environmental factors informative italian multicentre casecontrol study pediatric italian genetic environment exposure pedigree study designed investigate environmental exposures pediatriconset multiple sclerosis interaction geneticsobjectives collect evidence exposures environmental risk factors pediatriconset multiple sclerosis questionnaire developed italian population pedigree questionnaire presentedmethods pedigree questionnaire develops existing tool used casecontrol studies pediatriconset multiple sclerosis us americans translated adapted tested contents perceived relevance acceptability feasibility reliability population italian pediatric subjects parents recruited clinics general populationresults pedigree questionnaire contents overall deemed relevant study population acceptable 100 participants feasible least 98 pedigree questionnaire degree reliability ranged 56 72conclusion pedigree questionnaire proves efficient tool assess environmental exposures italian pediatric population encourage dissemination populationspecific questionnaires shared methodology optimize efforts ms etiological researchpmid34868629 pmcpmc8640303 doi101177 20552173211059048,0.0
association diseasemodifying treatment anticd20 infusion timing humoral response 2 sarscov2 vaccines patients multiple sclerosis jama neurol 2021 sep 23 doi 101001 jamaneurol20213609 online ahead printno abstractpmid34554185 doi101001 jamaneurol20213609,0.0
multiple sclerosis lesions segmentation multiple experts miccai 2016 challenge dataset neuroimage 2021 sep 23118589 doi 101016 jneuroimage2021118589 online ahead printabstractmri plays crucial role multiple sclerosis diagnostic patient followup particular delineation t2flair hyperintense lesions crucial although mostly performed manually tedious task many methods thus proposed automate task however sufficiently large datasets thorough expert manual segmentation still lacking evaluate methods present unique dataset ms lesions segmentation evaluation consists 53 patients acquired 4 different scanners harmonized protocol hyperintense lesions flair manually delineated patient 7 experts control t2 sequence gathered consensus segmentation evaluation provide raw preprocessed data split dataset training testing data latter including data scanner present training dataset strongly believe dataset will become reference ms lesions segmentation evaluation allowing evaluate many aspects evaluation performance unseen scanner comparison individual experts performance comparison challengers already used dataset etcpmid34563682 doi101016 jneuroimage2021118589,0.0
progressive functional neuroretinal affectation patients multiple sclerosis treated fingolimod j neuroophthalmol 2021 dec 1 41 4 e415e423 doi 101097 wno0000000000000991abstractbackground evaluate effect fingolimod visual function neuroretinal structures patients multiple sclerosis ms period 1 yearmethods longitudinal observational cohort study included 78 eyes 78 patients ms treated fingolimod subjects evaluated every 3 months 12 months compared 32 patients treated interferon beta patients examined highcontrast lowcontrast 25 125 visual acuity va contrast sensitivity vision csv using pellirobson csv1000e tests color vision farnsworth d15 lanthony d15 desaturated tests retinal structural measurements retinal nerve fiber layer rnfl ganglion cell layer gcl thickness using optical coherence tomography oct technologyresults patients ms treated fingolimod period 1 year showed significant reduction 100 125 contrast va p 0009 0008 respectively alteration contrast sensitivity color perception pellirobson test csv1000e test farnsworth d15 desaturated test lanthony d15 desaturated test p 0001 gcl thickness reduction p 0007 average macular central thickness increase 26 m p 0006 patients ms treated interferon beta show significant changes visual function tests neither macular thickness measurements showed significant reduction gcl rnfl thicknesses reduction neuroretinal structures observed oct significantly higher interferonbeta group patients treated fingolimod showed significant increase macular central thickness reduction low contrast vision p 0001 conclusions patients ms treated fingolimod clinically observable macular edema show significant change visual function parameters average macular central thickness increase compared treated interferon beta findings probably due subclinical macular edema produced fingolimod might considered indicator pharmacovigilance sphingosine1phosphate inhibitors improvedpmid34788241 doi101097 wno0000000000000991,0.0
quot sleeping beauty syndromequot psychosis precursory symptoms multiple sclerosis rare case literature review j nerv ment dis 2021 dec 1 209 12 933935 doi 101097 nmd0000000000001418abstractfrequently patients multiple sclerosis ms experience comorbid psychiatric symptoms mental disorders primarily occur simultaneously ms diagnosis however probability initial manifestation disease rare describe case 22yearold man previously hospitalized single psychotic episode alongside symptoms kleinelevin syndrome diagnosis acute transient psychotic disorders two years later diagnosed ms literature review possibility psychiatric episode overshadowing ms diagnosis presented clinicians always consider possibility underlying organicity case psychiatric presentation atypical features special attention given investigation process approach will lead early diagnosis organic disease can treated accordingly early possiblepmid34846357 doi101097 nmd0000000000001418,0.0
rituximab infusion timing cumulative dose hospitalization covid19 persons multiple sclerosis sweden jama netw open 2021 dec 1 4 12 e2136697 doi 101001 jamanetworkopen202136697no abstractpmid34851401 doi101001 jamanetworkopen202136697,0.0
papilledema patient treated multiple sclerosis j neuroophthalmol 2021 sep 30 doi 101097 wno0000000000001346 online ahead printno abstractpmid34629407 doi101097 wno0000000000001346,0.0
safety efficacy erythropoietin treatment patients optic neuritis tone randomised doubleblind multicentre placebocontrolled study summarybackgroundthe human cytokine erythropoietin conveys neuroprotection animal models shown ambiguous results phase 2 clinical trials patients optic neuritis assessed safety efficacy erythropoietin patients optic neuritis clinically isolated syndrome multicentre prospective randomised clinical trialmethodsthis randomised placebocontrolled doubleblind phase 3 trial conducted 12 tertiary referral centres germany included participants aged 1850 years within 10 days onset unilateral optic neuritis visual acuity 05 less without previous diagnosis multiple sclerosis participants randomly assigned 11 receive either 33000 iu erythropoietin placebo intravenously 3 days adjunct highdose intravenous methylprednisolone 1000 mg per day block randomisation performed trial statistician using sas code generated randomly varying block sizes stratified study site distributed using sealed envelopes trial participants study staff masked treatment assignment except trial pharmacist first primary outcome atrophy peripapillary retinal nerve fibre layer prnfl measured optic coherence tomography oct difference prnfl thickness affected eye week 26 unaffected eye baseline second primary outcome low contrast letter acuity week 26 measured 25 sloan chart score affected eye analysis performed full analysis set randomised participants treatment started least one followup oct measurement available safety analysed patients received least one dose trial medication trial registered clinicaltrialsgov nct01962571findings108 participants enrolled nov 25 2014 oct 9 2017 55 assigned erythropoietin 53 placebo five patients excluded primary analysis due receiving allocated medication withdrawn consent revised diagnosis loss followup yielding full analysis set 52 patients erythropoietin group 51 placebo group mean prnfl atrophy 1593 m sd 1491 erythropoietin group 1465 m 1560 placebo group adjusted mean treatment difference 102 m 95 ci 551 755 p076 mean low contrast letter acuity scores 4960 2131 erythropoietin group 4906 2193 placebo group adjusted mean treatment difference 403 1306 501 adverse events occurred 43 81 participants erythropoietin group 42 81 placebo group common adverse event headache occuring 15 28 patients erythropoietin group 13 25 patients placebo group serious adverse events occurred eight 15 participants erythropoietin four 8 placebo group one patient 2 erythropoietin group developed venous sinus thrombosis treated anticoagulants resolved without sequelaeinterpretationerythropoietin adjunct corticosteroids conveyed neither functional structural neuroprotection visual pathways optic neuritis future research focus modified erythropoietin administration assess efficacy independent corticosteroids investigate whether affects conversion optic neuritis multiple sclerosisfundinggerman federal ministry education research bmbf,0.0
humoral tcell response sarscov2 vaccination patients multiple sclerosis treated ocrelizumab jama neurol 2021 sep 23 doi 101001 jamaneurol20213599 online ahead printabstractimportance bcelldepleting therapies may affect development protective immune response following vaccination understanding ability develop vaccinespecific immunity covid19 patients multiple sclerosis ms treated bcelldepleting therapy importance clinical decisionsobjective assess sarscov2 vaccinespecific humoral cellular responses patients treated ocrelizumab compared healthy controlsdesign setting participants singlecenter study performed hadassah medical center jerusalem israel included patients ms treated ocrelizumab healthy controls untreated patients ms vaccination occurred december 2020 april 2021 participants donated blood 2 4 2 8 weeks second vaccine dose antibody tcell assessments respectivelyexposures participants received 2 doses bnt162b2 vaccine pfizer biontech completed studymain outcomes measures proportion patients treated ocrelizumab sarscov2specific serology tcell responses following vaccination participants underwent sarscov2 antibody testing 29 patients treated ocrelizumab 15 healthy controls evaluation sarscov2specific tcell responsesresults 112 participants 49 438 ms treated ocrelizumab 33 673 female mean sd age 479 133 years 23 205 ms treated diseasemodifying therapies 18 783 female mean sd age 49 134 years 40 357 healthy controls 25 625 female mean sd age 453 16 years twentysix 29 patients 897 treated ocrelizumab 15 15 healthy controls 100 sarscov2specific t cells following vaccination similar levels mean sd 154 76 143 63 spotforming cells respectively mean antibody titers positive serology rate lower group patients treated ocrelizumab mean sd antibody titers positive serology rate 262 492 3765 9076 au ml 10 40 25 20 49 408 s1 s2 receptorbinding domain respectively compared healthy controls mean sd antibody titers positive serology rate 283 100 12 712 9114 au ml 100 s1 s2 receptorbinding domain untreated patients mean sd antibody titers positive serology rate 2883 1138 10 877 9476 au ml 100 s1 s2 receptorbinding domain positive association time ocrelizumab infusion s1 s2 r 07 p 001 receptorbinding domain r 04 p 04 conclusion relevance study patients ms treated ocrelizumab generated comparable sarscov2specific tcell responses healthy controls lower antibody response following vaccination given potential role t cells protection severe disease reassuring will help physicians develop consensus guidelines regarding ms treatment era covid19 pandemicpmid34554197 doi101001 jamaneurol20213599,0.0
variation evolving optic neuritis j neuroophthalmol 2021 jul 23 doi 101097 wno0000000000001310 online ahead printabstractbackground typical natural history optic neuritis subjected important exceptions recognition exceptions led valuable insights regarding specific etiologies optic neuritis exceptions natural history recovering optic neuritis welldefined eg chronic relapsing inflammatory optic neuropathy exceptions natural history evolving optic neuritis less somethods medical records patients illustrating atypical course evolving optic neuritis reviewed retrospective manner patient treated least one authorsresults four patients identified illustrated atypical natural history incipient optic neuritis diagnoses included idiopathic optic neuritis seropositive neuromyelitis optica spectrum disease antimyelin oligodendrocyte glycoprotein antibody disease multiple sclerosis 1 patient features interest included atypical temporal relationship development pain onset clinical optic neuropathy unusually protracted duration pain unusually long duration worsening optic neuropathy stabilizationconclusions case series illustrates substantial clinical heterogeneity may observed evolution optic neuritis temporal relationship development pain onset clinical optic neuropathy duration pain duration worsening optic neuropathy stabilization subjected significant variability although patients optic neuritis present painful vision loss progresses 1 week less careful attention exceptions described herein may facilitate earlier recognition diagnostically challenging casespmid34310458 doi101097 wno0000000000001310,1.0
paediatric multiple sclerosis lesson terikids biological plausibility convincing evidence subgroup analyses indicate treatments proven efficacious adults multiple sclerosis generally effective patients younger active disease 1 findings give rationale use drugs paediatric multiple sclerosis put another way apparent reason effective treatments adults relapsingremitting multiple sclerosis effective children arguably important requirement advance care paediatric patients multiple sclerosis assessment longterm safety ensure treatment childhood adolescence expose patients future risk ways safety efficacy drugs might investigated patients paediatric multiple sclerosis discussed extensively consensus paper international paediatric multiple sclerosis study group ipmssg 2,0.0
acromiohumeral distance supraspinatus tendon thickness people shoulder impingement syndrome compared asymptomatic age gendermatched participants case control study background shoulder impingement syndrome sis common form shoulder pain conservative surgical treatments sis often effective one surgical intervention subacromial decompression aimed widening subacromial space sas better understanding changes sas may help explain relative ineffectiveness current interventionsobjective measure acromiohumeral distance ahd supraspinatus tendon thickness stt people sis using case control studymethodsthe ahd stt 39 participants sis 3 months 39 age gender dominant arm matched controls measured using ultrasound imaging betweengroup differences ahd stt compared using ttests linear regression used determine relationship ahd stt measures group covariateresultscompared controls mean age 557 years sd 106 individuals sis mean age 571 years sd 111 significantly larger ahd mean difference 214 mm 95 ci 121 307 p 0001 stt mean difference 125 mm 95 ci 060 190 p 0001 linear regression model indicated association ahd stt 059 95 ci 029 089 p 001 r2 035 n 78 suggesting stt increases size ahdconclusionindividuals sis larger ahd greater stt controls results suggest sas already wider people sis symptoms associated sis may related increased stt smaller sas,0.0
health disparities inequities social determinants health multiple sclerosis related disorders us review jama neurol 2021 oct 4 doi 101001 jamaneurol20213416 online ahead printabstractimportance empirical evidence social determinants health sdoh impact health outcomes black hispanic latinx individuals us recently sdoh risen top essential intervention targets help alleviate racial ethnic disparities neuromyelitis optica spectrum disorder nmosd disproportionately affects black individuals multiple sclerosis ms seen recent shift select racial groups unclear degree sdoh investigated contribute racial ethnic health disparities inequitiesobservations narrative review provides contemporary synthesis sdoh associated racial ethnic health disparities inequities ms nmosd autoimmune disorders myelin oligodendrocyte glycoprotein antibody mogab associated disease immunemediated neurological diseases chosen capacity high burden society complementary sdohassociated challenges among minority populations paucity research addressing inequities role sdoh ms nmosd noted despite findings black individuals higher risk developing ms nmosd associated mortality compared white individuals greater health disparities also found lower income education lower health literacy negative illness perceptions ms studies mogab disorders foundconclusions relevance increased efforts needed better understand role sdoh racial ethnic health disparities inequities ms nmosd emerging autoimmune disorders includes developing research frameworks aimed understanding magnitude interrelationships sdoh better develop systembased multilevel interventions across spectrum care neurological conditionspmid34605866 doi101001 jamaneurol20213416,1.0
novel transition clinic structure adolescent young adult patients childhood onset rheumatic disease improves transition outcomes transition health care pediatric adult providers adolescents young adults chronic disease associated poor outcomes despite importance transition 80 th,0.0
frequency new silent mri lesions myelin oligodendrocyte glycoprotein antibody disease aquaporin4 antibody neuromyelitis optica spectrum disorder jama netw open 2021 dec 1 4 12 e2137833 doi 101001 jamanetworkopen202137833abstractimportance multiple sclerosis magnetic resonance imaging mri new silent lesions contribute diagnostic criteria prognostic value used treatment monitoring aquaporin4 antibody neuromyelitis optica spectrum disorder aqp4nmosd rare attacks frequency association relapses adults myelin oligodendrocyte glycoprotein antibody disease mogad still unclearobjective examine frequency characteristics mri new silent lesions mogad aqp4nmosddesign setting participants retrospective cohort study analyzed clinical mri data 404 patients mogad aqp4nmosd february 1 1994 april 1 2021 data prospectively recorded oxford nmosd clinical database followup study conducted oxford national referral center nmosd participants included patients mogad aqp4nmosd treated within oxford national nmo specialist serviceexposures seropositive mogad aqp4nmosd patients mris attacks remission phase diseasemain outcomes measures frequency new silent lesions detected either attack mris acute clinical event remission mris performed outside relapse least 3 months last attack median time next relapse presence definite reference mri performed least 4 weeks last attack onset probable reference mri performed last attack new silent lesions remission mris also evaluatedresults one hundred eightytwo mogad patients 222 aqp4nmosd patients included mogad patients 113 62 female median age onset 28 years range 272 median followup 52 months range 11253 aqp4nmosd patients 189 85 female median age onset 43 years range 282 median followup 875 months range 11260 mogad patients 296 attack mri sessions 167 remission mri sessions new attack silent lesions found 97 296 33 attack mri sessions whereas new remission silent lesions found 5 167 30 remission mri sessions median time remission scan next relapse presence definite probable new remission lesions 2 months iqr 16 whereas absence new remission lesions 73 months iqr 20104 hazard ratio 2386 95 ci 7517579 p 001 aqp4nmosd patients 470 attack mri sessions 269 remission mri sessions new attack silent lesions detected 88 470 187 attack mri sessions whereas new remission silent lesions found 7 269 26 remission mri sessions median time remission scan next relapse presence definite probable new remission lesions 5 months iqr 26 whereas absence new remission lesions 85 months iqr 29167 hazard ratio 2123 95 ci 8055365 p 001 conclusions relevance contrast reported multiple sclerosis results cohort study suggest new remission silent lesions rare followup scans mogad aqp4nmosd appear indicate high risk imminent relapsepmid34878547 doi101001 jamanetworkopen202137833,1.0
mtans multiscale mean teacher combined adversarial network shapeaware embedding semisupervised brain lesion segmentation neuroimage 2021 sep 8118568 doi 101016 jneuroimage2021118568 online ahead printabstractthe annotation brain lesion images key step clinical diagnosis treatment wide spectrum brain diseases recent years segmentation methods based deep learning gained unprecedented popularity leveraging large amount data highquality voxellevel annotations however due limited time clinicians can provide cumbersome task manual image segmentation semisupervised medical image segmentation methods present alternative solution require labeled samples training paper propose novel semisupervised segmentation framework combines improved mean teacher adversarial network specifically framework consists student model teacher model segmenting target generating signed distance maps object surfaces ii discriminator network extracting hierarchical features distinguishing signed distance maps labeled unlabeled data besides based two different adversarial learning processes multiscale feature consistency loss derived student teacher models proposed shapeaware embedding scheme integrated framework evaluated proposed method public brain lesion datasets isbi 2015 isles 2015 brats 2018 multiple sclerosis lesion ischemic stroke lesion brain tumor segmentation respectively experiments demonstrate method can effectively leverage unlabeled data outperforming supervised baseline stateoftheart semisupervised methods trained labeled data proposed framework suitable joint training limited labeled data additional unlabeled data expected reduce effort obtaining annotated imagespmid34508895 doi101016 jneuroimage2021118568,0.0
application magnetic resonance imaging patients concussion clinical emergency comput math methods med 2021 dec 1 20217749540 doi 101155 2021 7749540 ecollection 2021abstractconcussion syndrome common disease neurosurgery incidence ranks first among traumatic brain injuries cognitive dysfunction one common functional impairments concussion syndrome neuroimaging content assessments concussion patients healthy control subjects used study uses mri technology evaluate brain pictures concussion patients moreover paper separately evaluates scores concussion syndrome group healthy control group multiple functional aspects performs independent sample ttest statistics two scores addition paper uses restingstate fmri study changes functional connectivity medial prefrontal lobe patients pcs certain significance revealing cognitive dysfunction concussion certain effect improving clinical emergency diagnosis treatment concussionpmid34899970 pmcpmc8654544 doi101155 2021 7749540,0.0
pet ownership multiple sclerosis covid19 int j environ res public health 2021 dec 1 18 23 12683 doi 103390 ijerph182312683abstractbackground multiple sclerosis ms associated lower quality life reduced social participation decreased selfefficacy covid19 pandemic documented effects health wellbeing people without ms previous research demonstrated positive impact pets can people living longterm conditions objectives explore rates pet ownership pet attachment people living ms pet ownership associations quality life satisfaction social roles selfefficacy scores explore effects covid19 outbreak peoples perceived relationships pets materials methods postal questionnaire distributed members local ms register control group people without ms questionnaire assessed quality life satisfaction social roles selfefficacy perceived roles pets petrelated concerns experienced covid19 pandemic results apparent difference attachment pets found patient control groups pet ownership level attachment associated differences quality life selfefficacy scores people living ms using multiple regression analysis pet ownership associated decrease satisfaction participation social roles estimated effect small compared diagnosis ms unemployed participants reported pets positive roles pandemic reported petrelated concern access veterinary treatment conclusion pet owners without ms reported subjective benefits wellbeing pet ownership covid19 although analysis suggested pet ownership associated reduction satisfaction social roles study several limitations suggestions made future workpmid34886405 doi103390 ijerph182312683,0.0
analysis clinical characteristics prognosis traumatic brain injury papua new guinea comput math methods med 2021 dec 1 20214948664 doi 101155 2021 4948664 ecollection 2021abstractobjective evaluate clinical characteristics prognosis tbi patients 2016 2019 admitted port moresby general hospital pmgh papua new guinea png compare results previous researches analyze current clinical characteristics prognosismethods retrospective study performed 389 tbi patients port moresby general hospital pmgh 48month period january 2016 december 2019 clinical radiographic data collected patients followed least 3 months outcomes assessed using glasgow outcome scale gos univariate multivariate logistic regressions performed analyze prognosis intracranial infection patients well effect surgery prognosis tbi patientsresults average age 389 tbi patients 249 years old common age 1840 years old accounting 555 proportion male patients 794 proportion juvenile patients 18 years 308 primary cause injury fighting brawling 380 admission patients average gcs score 91 patients severe tbi accounted 468 overall 321 patients good prognosis mortality rate 139 54 cases analyzing relationship surgical treatment prognosis 303 patients moderate severe tbi statistical significance univariate logistic regression analyses poor prognosis included gender gcs multiple injuries rotterdam ct scores intracranial infection univariate logistic regression analyses intracranial infection included gcs open brain trauma postoperative drainage timeconclusion despite secular trend towards reduced incidence tbi prognosis moderate severe tbi patients received surgery showed significant improvement indicating png backward developing country faced huge problem tbi prevention controlpmid34899966 pmcpmc8654555 doi101155 2021 4948664,0.0
safety efficacy teriflunomide paediatric multiple sclerosis terikids multicentre doubleblind phase 3 randomised placebocontrolled trial summarybackgroundtherapeutic options children multiple sclerosis scarce teriflunomide approved 80 countries treatment adults relapsing multiple sclerosis terikids study examined safety efficacy teriflunomide children relapsing multiple sclerosismethodsthe terikids trial multicentre phase 3 doubleblind parallelgroup randomised placebocontrolled study conducted 57 clinical centres 22 countries asia europe middle east north africa north america trial enrolled patients aged 1017 years diagnosed relapsing multiple sclerosis least one relapse year preceding screening least two relapses 2 years preceding screening patients randomly assigned 21 oral teriflunomide dosage equivalent 14 mg adults matching placebo using interactive web voice response system 96 weeks personnel sites patients masked study treatment doubleblind period early entry subsequent 96week openlabel extension phase possible end doubleblind period patients confirmed clinical relapse high mri activity least five new enlarged t2 lesions week 24 followed least nine new enlarged t2 lesions week 36 least five new enlarged t2 lesions weeks 36 48 weeks 48 72 primary endpoint time first confirmed clinical relapse end doubleblind period key secondary imaging endpoints number new enlarged t2 lesions number gadoliniumenhancing lesions per mri scan efficacy endpoints analysed intentiontotreat population safety assessed patients randomly assigned treatment exposed doubleblind study medication study registered clinicaltrialsgov trial number nct02201108 closed recruitment additional optional openlabel extension ongoingfindingsbetween july 24 2014 date last patient visit oct 25 2019 185 patients screened eligibility 166 90 enrolled 109 randomly assigned teriflunomide 57 randomly assigned placebo 102 94 109 53 93 57 completed doubleblind period switch ongoing openlabel extension high mri activity frequent anticipated placebo group 14 13 109 patients teriflunomide group vs 15 26 57 placebo group decreasing power study 96 weeks difference time first confirmed clinical relapse teriflunomide compared placebo hazard ratio 066 95 ci 039111 p029 teriflunomide reduced number new enlarged t2 lesions versus placebo 55 relative risk 045 95 ci 029071 p000061 number gadoliniumenhancing lesions 75 relative risk 025 013051 p00001 adverse events occurred 96 88 patients teriflunomide group 47 82 patients placebo group serious adverse events occurred 12 11 patients teriflunomide group 6 11 patients placebo group nasopharyngitis upperrespiratorytract infection alopecia paraesthesia abdominal pain increased blood creatine phosphokinase frequent teriflunomide placebo doubleblind phase four patients teriflunomide group pancreatic adverse events two acute pancreatitis two pancreatic enzyme elevation three events led treatment discontinuationinterpretationno significant difference time first confirmed clinical relapse found possibly patients expected switched doubleblind openlabel treatment period high mri activity key secondary imaging analyses prespecified sensitivity analysis probability relapse high mri activity suggest teriflunomide might beneficial effects children relapsing multiple sclerosis reducing risk focal inflammatory activityfundingsanofi,0.0
sustained erbb activation causes demyelination hypomyelination driving necroptosis mature oligodendrocytes apoptosis oligodendrocyte precursor cells oligodendrocytes vulnerable genetic environmental insults injury leads demyelinating diseases roles erbb receptors maintaining cns myelin integrity largely unknown overactivate erbb receptors mediate signaling either neuregulin nrg epidermal growth factor egf family growth factors found synergistic activation caused deleterious outcomes white matter sustained erbb activation induced tetracyclinedependent mouse tool plptta resulted demyelination axonal degeneration oligodendrocyte precursor cell opc proliferation astrogliosis microgliosis white matter moreover hypermyelination inflammatory pathologic events contrast sustained erbb activation induced another tetracyclinedependent mouse tool sox10+ rtta caused hypomyelination corpus callosum optic nerve appeared developmental deficit associate opc regeneration astrogliosis microgliosis tracing differentiation states cells expressing tetracyclinecontrolled transcriptional activator tta reverse tta rtta dependent transgene pulselabeled reporter proteins vitro vivo found plptta targeted mainly mature oligodendrocytes mos whereas sox10+ rtta targeted opcs newlyformed oligodendrocytes nfos distinct phenotypes mice erbb overactivation induced plptta sox10+ rtta consolidated nonoverlapping targeting preferences oligodendrocyte lineage enabled us demonstrate erbb overactivation mos induced necroptosis caused inflammatory demyelination whereas opcs induced apoptosis caused noninflammatory hypomyelination early interference aberrant erbb activation ceased oligodendrocyte deaths restored myelin development mice study suggests aberrant erbb activation upstream pathogenetic mechanism demyelinating diseases providing potential therapeutic targetsignificance statement primary oligodendropathy one etiologic mechanisms multiple sclerosis oligodendrocyte necroptosis pathologic hallmark disease moreover demyelinating disease now broad concept embraces schizophrenia white matter lesions emerging feature erbb overactivation implicated schizophrenia genetic analysis postmortem studies study suggests etiologic implications erbb overactivation myelin pathogenesis elucidates pathogenetic mechanisms,1.0
topiramateinduced severe electrolyte abnormalities hypernatremia leading central pontine myelinolysis bmj case rep 2021 nov 30 14 11 e245870 doi 101136 bcr2021245870abstractcentral pontine myelinolysis cpm develops due acute hypernatremia normal baseline serum sodium setting electrolyte abnormalities induced topiramate use topiramate commonly used medication several indications including migraines myoclonic jerks seizures reported cause renal tubular acidosis severe electrolyte abnormalities turn predispose patients neuropathology via renal concentration defects osmotic shifts patient 55yearold woman history multiple sclerosis myoclonus topiramate several years presented weakness found profoundly hypokalemic went develop changes mental status motor deficits evidence cpm mri hospitalisation surprisingly patient never hyponatremia however acute rise serum sodium normal baseline fluid resuscitation normal saline hypotension admissionpmid34848414 doi101136 bcr2021245870,1.0
circulatory antioxidant oxidative stress markers correlation demographics cognitive functions multiple sclerosis patients abstractbackgroundmultiple sclerosis ms common nontraumatic cause disability younger adults ms can presented wide range symptoms cognitive impairment ci oxidative stress oxs major basis pathogenesis ms positive correlation oxs factors progression disease ms patients limited studies regarding role oxs msrelated ci study exploratory analysis assess role endogenous antioxidants oxs factors cognitive function severity disability due ms demographic findings sample ms patientsmethodsadult 18 years old patients definite diagnosis ms based 2017 revised macdonald criteria included study neurophysiological assessment conducted using validated persian version minimal assessment cognitive function multiple sclerosis macfims battery composed seven different tests based structure battery ci defined failure least two different components macfims battery patients separated two groups ci nonci examined antioxidant factors included catalase activity cat glutathione peroxidase 1 gpx1 glutathione peroxidase 2 gpx2 reduced glutathione gsh superoxide dismutase sod serum total antioxidant capacity tac malondialdehyde mda also measured oxs markerresults71 patients involved study type ms relapsingremitting ms rrms 8028 participants disease duration p001 type ms p001 edss score p001 different ci nonci groups significant differences cat p080 gpx1 p071 gpx2 p041 gsh p096 tac p013 sod p037 mda p082 significant difference rrms progressive ms pms patients levels gpx1 p001 gpx2 p001 sod p001 observed also found higher circulatory levels cat p002 tac p001 male ms patients found significant correlations aging cat r028 p001 gpx1 r036 p001 gpx2 r034 p001 sod r040 p001 edss duration disease relapse rate number impaired cognitive tasks correlated investigated oxs antioxidant factors p005 terms detailed investigation associations macfims battery components levels oxs antioxidant factors significant relations regard p005 based logistic regression multivariate analysis disease duration p003 gpx1 p001 independently associated ci ms patients sampleconclusionthe circulatory levels gpx1 gpx2 sod significantly different rrms pms patients neither endogenous antioxidants mda oxs biomarker associated cognitive function level physical disability ms patients limitations study suggest need future studies larger sample ms patients,0.0
subjective global assessment malnutrition dysphagia effect clinical paraclinical outcomes elderly ischemic stroke patients communitybased study background malnutrition result insufficient intake uptake nutrition leads increasing rate chronic diseases stroke stroke one common causes death western countries increasing trend attracted lots attention regard seems logical focus modifiable risk factors nutrition order reduce resulting complications accordingly study aimed evaluating nutrition status stroke patients estimate relationship clinical outcomes strokemethodsin present crosssectional study 349 patients recruited nutrition assessment performed using patientgenerated subjective global assessment pgsga addition national institutes health stroke scale nihss modified rankin scale mrs biochemical tests performedresultsour findings elucidated significant positive correlation mrs pgsga consciousness score well negative correlation bmi calf circumference midarm circumference triceps skinfold admission time p 0002 moreover direct correlation found mrs pgsga consciousness score discharge time p 0001 contrast inverse correlation established mrs midarm circumference p 002 furthermore univariate analysis indicated significant associations mrs 3 age 102 95ci 100104 pgsga 108 95ci 103113 nihss 104 95ci 102107 dysphagia 169 95ci 103277 consciousness 148 95ci 107204 midarm circumference 095 95ci 090100 addition associations remained significant multivariate analysis pgsga 107 95ci 100113 nihss 104 95ci 101107 conclusionthis study revealed positive correlation mrs consciousness status pgsga score well negative one mrs mac discharge time,0.0
reduced expression mitochondrial fumarate hydratase progressive multiple sclerosis contributes impaired vitro mesenchymal stromal cellmediated neuroprotection abstractbackgroundcellbased therapies multiple sclerosis ms including employing autologous bone marrowderived mesenchymal stromal cells msc examined clinical trials however recent studies identified abnormalities ms bone marrow microenvironmentobjectivewe aimed compare secretome msc isolated control subjects cmsc people ms msmsc explore functional relevance findingsmethodswe employed high throughput proteomic analysis enzymelinked immunosorbent assays immunoblotting well vitro assays enzyme activity neuroprotectionresultswe demonstrated progressive ms msc secretome lower levels mitochondrial fumarate hydratase mfh exogenous mfh restores vitro neuroprotective potential msmsc furthermore msmsc expresses reduced levels fumarate hydratase fh downstream reduction expression master regulators oxidative stressconclusionsour findings evidence dysregulation bone marrow microenvironment progressive ms respect antioxidative capacity immunoregulatory potential given clinical utility fumaric acid ester dimethyl fumarate relapsingremitting ms findings potential implication understanding ms pathophysiology personalised therapeutic intervention,1.0
recovery covid19 multiple sclerosis prospective longitudinal cohort study united kingdom multiple sclerosis register neurol neuroimmunol neuroinflamm 2021 nov 30 9 1 e1118 doi 101212 nxi0000000000001118 print 2022 janabstractbackground objectives understand course recovery coronavirus disease 2019 covid19 among patients multiple sclerosis ms determine predictors including patients precovid19 physical mental health statusmethods prospective longitudinal cohort study recruited patients ms reported covid19 march 17 2020 march 19 2021 part united kingdom ms register ukmsr covid19 study participants used online questionnaires regularly update covid19 symptoms recovery status duration symptoms fully recovered questionnaires date stamped estimation covid19 symptom duration recovered last followup ukmsr holds demographic uptodate clinical data participants well webbased expanded disability status scale webedss hospital anxiety depression scale hads scores association factors recovery covid19 assessed using multivariable cox regression analysisresults 7 977 patients ms participated ukmsr covid19 study 599 reported covid19 prospectively updated recovery status twentyeight hospitalized participants excluded least 165 participants 297 longstanding covid19 symptoms 4 weeks 69 124 12 weeks participants precovid19 webedss scores 7 participants probable anxiety depression hads scores 11 covid19 onset women less likely report recovery covid19discussion patients ms affected postacute sequelae covid19 preexisting severe neurologic impairment mental health problems appear increase risk findings can implications tailoring postcovid19 rehabilitationpmid34848503 doi101212 nxi0000000000001118,0.0
covid19 infection fingolimod siponimodtreated patients case series neurol neuroimmunol neuroinflamm 2021 nov 30 9 1 e1092 doi 101212 nxi0000000000001092 print 2021 novabstractbackground objectives descriptive analysis covid19 infection patients multiple sclerosis ms receiving fingolimod siponimodmethods reviewed cases covid19 postmarketing ongoing clinical trials reported novartis december 27 2020results december 27 2020 283 cases reported fingolimodtreated patients mean age 44 years n 224 range 1169 years 190 women 161 cases available information 138 asymptomatic 6 mild 100 moderate 32 50 cases required hospitalization last followup 140 patients reported recovered recovering condition unchanged 22 deteriorated 3 patients 4 patients fatal outcome information available 114 patients 54 cases covid19 reported siponimodtreated patients 45 postmarketing setting 9 ongoing openlabel clinical trial mean age 54 years n 45 range 3170 30 women 28 cases available information 24 asymptomatic 2 mild 17 moderate 5 9 cases required hospitalization last followup 27 patients reported recovered recovering condition remained unchanged 1 3 patients fatal outcome information available 23 patientsdiscussion based review available information risk severe covid19 patients receiving fingolimod siponimod seems similar reported general population ms population covid19 however limitations spontaneous reporting especially missing data considered interpretation observationspmid34848501 doi101212 nxi0000000000001092,0.0
proceedings inaugural canadian healthcare navigation conference forum sharing innovations best practices navigation services background individuals experiencing chronic illnesses face many physical emotional social strains result illnesses trying navigate unfamiliar territory healthcare system navigation strategy can help people facing complex care needs barriers care finding accessing needed supports health care system navigators provide patientcentred service guiding individuals care plans overcoming barriers care navigation supports individuals experiencing complex care needs shown significant promise gaining traction across canadamethodsthe canadian healthcare navigation conference first event kind canada bring together navigation researchers service providers students decision makers individuals lived experience share lessons learned promising practices research findings event cohosted family navigation project sunnybrook health sciences centre navicare soinsnavi university new brunswick took place virtually april 1516 2021resultsthis event spanned two days began keynote address one researcher medical professional navigation another individual lived experience involved advocacy canadian healthcare concurrent oral presentations variety presenters held following keynote presentation poster session held end first day panel presentation rounded second day concurrent poster presentations covered range topics pertaining approaches navigation navigator roles evaluation quality improvement lived experience navigation navigation context covid19 pandemic panel presentation focused identifying navigation field progressed canada identifying crucial next steps navigation next steps determined 1 agreement navigationrelated definitions 2 regulation training 3 equity diversity inclusion accessibility 4 integrating lived experience 5 regional coordinationconclusionthis conference important first step creating shared national conversation navigation services can continue develop implement share best evidence practices field,0.0
bacterial variation oral microbiota multiple sclerosis patients plos one 2021 nov 30 16 11 e0260384 doi 101371 journalpone0260384 ecollection 2021abstractbackground microorganisms oral cavity called oral microbiota microbiome consists total genome content microorganisms host interaction host microorganisms important nervous system development nervous diseases autism alzheimer parkinson multiple sclerosis ms bacterial infections environmental factor ms pathogenesis play role t helper 17 th17 increase enhancing production proinflammatory cytokines interlukin21 il21 il17 il 22 oral microbiota consists diverse populations cultivable uncultivable bacterial species denaturing gradient gel electrophoresis dgge acceptable method identification uncultivable bacteria study compared bacterial population diversity oral cavity ms healthy peoplemethods october march 2019 samples taken kermanshah university medical sciences ms patients center total 30 samples taken ms patients another 30 samples taken healthy people phenotypic tests used identify bacteria pure cultures obtained dna extracted 1 ml saliva pcr products produced primers electrophoresed polyacrylamide gelsresults genera staphylococcus actinomyces fusobacterium bacteroides porphyromonas prevotella veillonella propionibacterium uncultivable bacteria accession number mw88091925 jq4774161 kf0748881 several unculturable strains significantly abundant ms group lactobacillus peptostreptococcus prevalent normal healthy group according logistic regression methodconclusion oral microorganisms may alleviate exacerbate inflammatory condition impact ms disease pathogenesis may assumed controlling oral infections may result reduction ms disease progressionpmid34847159 doi101371 journalpone0260384,0.0
effective therapy highly active pediatric multiple sclerosis ideggyogy sz 2021 nov 30 74 1112 413424 doi 1018071 isz740413abstractmultiple sclerosis ms typically disease young adults childhood ms can defined patients 18 years age although authors set limit age 16 formerly known earlyonset multiple sclerosis juvenile multiple sclerosis seen 35 ms patients nowadays owing everevolving better diagnostic tools welltraced strictly defined diagnostic criteria childhood ms showing increasing incidence worldwide 005285 100 000 ms characterized recurrent episodes central nervous system demyelination separated space time childhood almost exclusively relapsingremitting rr type ms occurs based experience adults goal pediatric population also early diagnosis initiate adequate dmt soon possible achieve symptom relief good quality life based efficacy safety studies adult population interferon 1a glatiramer acetate first approved fda ema treatment childhood ms also increased relapse rate rapid progression childhood ms unfavorable therapeutic response nearly 45 first dmt necessitated testing effective secondline drugs population 18 years age paradigms connect although natalizumab reported effective welltolerated highly active rrms childhood evidence based studies yet available patients treatment started article report successful treatment three active rrms patients individually authorized offlabel use natalizumabpmid34856082 doi1018071 isz740413,1.0
oral contraceptives modify risk second attack disability accrual prospective cohort women clinically isolated syndrome early multiple sclerosis abstractobjectiveto evaluate whether oral contraceptive oc use associated risk second attack disability accrual women clinically isolated syndrome cis early multiple sclerosis ms methodsreproductive information women included barcelona cis prospective cohort collected selfreported crosssectional survey examined relationship oc exposure risk second attack confirmed expanded disability status scale 30 using multivariate cox regression models adjusted age topography cis oligoclonal bands baseline brain t2 lesions body size menarche smoking diseasemodifying treatment dmt oc dmt exposures considered timevarying variables findings confirmed sensitivity analyses using propensity score modelsresultsa total 495 women included 389 786 referred ever use oc 341 689 started oc cis exposure oc associated second attack adjusted hazard ratio ahr 073 95 confidence interval ci 033161 disability accrual ahr 081 95 ci 017376 sensitivity analyses confirmed resultsconclusionoc use modify risk second attack disability accrual patients cis early ms considered timedependent exposure adjusted potential confounders,0.0
determining minimal important change 6minute walking test multiple sclerosis patients using predictive modelling anchorbased method abstractbackground minimal important change mic 6minute walk test 6mwt clear patients multiple sclerosis ms hampering treatment evaluation aim study therefore determine mic 6mwt ms patientsmethods ms patients 6mwt using instruction walk comfortable speed twice approximately one year second 6mwt completed 3point anchor question micadjusted 95 confidence interval ci calculated predictive modelling method bootstrappingresults 118 ms patients mean age 482 years 237 men included september 2018 october 2019 mean 6mwt distance 468 112m baseline 469 115m one year later twentythree 195 patients answered walking distance improved 43 364 answered worsened micadjusted improvement 197m 95ci 98309m found deterioration 72 95ci 33182m conclusions using sophisticated statistical method micadjusted 6mwt ms patients 197m improvement 72m deterioration knowledge allows physiotherapists physicians evaluate treatment led meaningful improvement ms patients walking patients deteriorated,0.0
coping strategies impact quality life physical disability people multiple sclerosis j clin med 2021 nov 29 10 23 5607 doi 103390 jcm10235607abstractthe aim study investigate impact coping strategies healthrelated quality life hrqol physical disability assessed expanded disability status scale edss people multiple sclerosis pwms pwms asked focus ms diagnosis core stressor one hundred eight pwms completed coping responses inventoryadult form criadult multiple sclerosis quality life29 msqol29 depression anxiety stress scale21 dass21 multiple regression analyses first block edss disease duration dass21 revealed physical msqol29 positively associated alternative rewards negatively resigned acceptance criadult mental msqol29 positively associated problemsolving negatively emotional discharge expanded disability status scale edss first block disease duration general distress negatively associated positive reappraisal analysis covariance ancova revealed pwms lower physical disability showed higher scores positive reappraisal lower scores emotional discharge pwms higher physical disability coping strategies can play role hrqol physical disability pwms beyond edss disease duration general distress psychological interventions considered pwms since time diagnosis promote engagement adaptive coping strategies contrast maladaptive onespmid34884308 doi103390 jcm10235607,0.0
characteristics covid19 patients multiple sclerosis abstractbackground regarding high prevalence multiple sclerosis ms covid19 iran multicenter study covid19 iranian ms patients carried address concerns populationmethods data ms patients covid19 nine provinces iran entered webbased registry system july 2020 march 2021 among covid19 symptoms dyspnea altered mental status resulting hospital admission considered severeresults total 397 eligible patients identified addition 310 78 female mean age 365 95 294 74 patients relapsing remitting form also four patients 1 expired due covid19 infection mean duration admission hospitalized patients 9 53 days mri performed 111 28 patients developing covid19 mri changes observed 27 24 cases ms drug changed 26 6 patients steroid use past three months 243 95 ci 1003 588 p value 0049 anticd20s 403 95 ci 241 668 p value 0001 showed significant association severe covid19 symptomsconclusion death rate covid19 among ms patients 1 lower overall death rate pandemic iran 3 received steroid past three months may increased risk severe forms covid19 still doubts effect anti cd20s covid19 severity,0.0
cenerimod selective s1p1 receptor modulator improves organspecific disease outcomes animal models sjgrens syndrome background sjgrens syndrome systemic autoimmune disease characterized immune cells predominantly infiltrating exocrine glands frequently forming ectopic lymphoid structures structures drive local functional immune response culminating autoantibody production tissue damage associated severe dryness mucosal surfaces salivary gland hypofunction cenerimod potent selective orally active sphingosine1phosphate receptor 1 modulator inhibits egress lymphocytes circulation based mechanism action cenerimod efficacy evaluated two mouse models sjgrens syndromemethodscenerimod administered two established models sjgrens syndrome firstly inducible acute viral sialadenitis model c57bl 6 mice secondly spontaneous chronic sialadenitis mrl lpr mouse model effects cenerimod treatment evaluated flow cytometry immunohistochemistry histopathology immunoassays comparisons groups made using mannwhitney testresultsin viral sialadenitis model cenerimod treatment reduced salivary gland immune infiltrates leading disaggregation ectopic lymphoid structures reduced salivary gland inflammation preserved organ function mrl lpr mouse model cenerimod treatment decreased salivary gland inflammation reduced t cells proliferating plasma cells within salivary gland ectopic lymphoid structures resulting diminished diseaserelevant autoantibodies within salivary glandsconclusionstaken together results suggest cenerimod can reduce overall autoimmune response improve clinical parameters salivary glands models sjgrens syndrome consequently may reduce histological clinical parameters associated disease patients,0.0
pharmacological sarm1 inhibition protects axon structure function paclitaxelinduced peripheral neuropathy brain 2021 may 8awab184 doi 101093 brain awab184 online ahead printabstractaxonal degeneration early ongoing event causes disability disease progression many neurodegenerative disorders peripheral central nervous systems chemotherapyinduced peripheral neuropathy cipn major cause morbidity main cause dose reductions discontinuations cancer treatment preclinical evidence indicates activation wallerianlike degeneration pathway driven sarm1 responsible axonopathy cipn sarm1 central driver evolutionarily conserved program axonal degeneration downstream chemical inflammatory mechanical metabolic insults axon sarm1 contains intrinsic nadase enzymatic activity essential prodegenerative functions making compelling therapeutic target treat neurodegeneration characterized axonopathies peripheral central nervous systems small molecule sarm1 inhibitors potential prevent axonal degeneration peripheral central axonopathies provide transformational diseasemodifying treatment disorders using biochemical assay sarm1 nadase identified novel series potent selective irreversible isothiazole inhibitors sarm1 enzymatic activity protected rodent human axons vitro sciatic nerve axotomy sna observed irreversible sarm1 inhibitors decreased rise nerve cadpr plasma neurofilament light chain nfl released injured sciatic nerves vivo mouse paclitaxel model cipn determined sarm1 ko mice prevented loss axonal function assessed sensory nerve action potential snap amplitudes tail nerve gene dosagedependent manner cipn model irreversible sarm1 inhibitors prevented loss intraepidermal nerve fibers induced paclitaxel provided partial protection axonal function assessed snap amplitude mechanical allodyniapmid33964142 doi101093 brain awab184,0.0
undetectable sarscov2 active adaptive immunitypostvaccination postcovid19 severe diseaseafter immunosuppressants use bmj case rep 2021 nov 29 14 11 e246308 doi 101136 bcr2021246308abstractsince beginning covid19 vaccination new jersey december 2020 observed multiple cases undetectable adaptive immunity postvaccination postcovid19 infection patients using immunosuppressants present three cases patients using immunosuppressants mycophenolate tacrolimus renal transplant ocrelizumab multiple sclerosis rituximab peripheral ulcerative keratitis three patients admitted acute respiratory distress syndrome ards covid19 pneumonia two patients reported received full covid19 vaccination prior admission one unvaccinated patient required readmission findings showed patients tested negative sarscov2 igm spike cov2 igg nucleocapsid antibodies three patients treated standardofcare remdesivir dexamethasone convalescent plasma two recovered successfully one patient died respiratory failure secondary worsening ards covid19 pneumonia highlight challenges treating immunosuppressed patients covid19 pneumonia era dissemination information paramount helping doctors standardise improve quality care patientspmid34844968 doi101136 bcr2021246308,0.0
dimethyl fumarate treatment restrains antioxidative capacity t cells control autoimmunity brain 2021 nov 29 144 10 31263141 doi 101093 brain awab307abstractdimethyl fumarate approved treatment relapsingremitting multiple sclerosis exerts pleiotropic effects immune cells well cns resident cells show dimethyl fumarate exerts profound alteration metabolic profile human cd4+ well cd8+ t cells restricts antioxidative capacities decreasing intracellular levels reactive oxygen species scavenger glutathione causes increase mitochondrial reactive oxygen species levels accompanied enhanced mitochondrial stress response ultimately leading impaired mitochondrial function enhanced mitochondrial reactive oxygen species levels result enhanced tcell apoptosis vitro well dimethyl fumaratetreated patients key wellknown immunomodulatory effects dimethyl fumarate vitro animal model multiple sclerosis ie experimental autoimmune encephalomyelitis indeed dimethyl fumarate immunemodulatory effects t cells completely abrogated pharmacological interference mitochondrial reactive oxygen species production data shed new light dimethyl fumarate bona fide immunemetabolic drug targets intracellular stress response activated t cells thereby restricting mitochondrial function energetic capacity providing novel insight role oxidative stress modulating cellular immune responses t cellmediated autoimmunitypmid34849598 doi101093 brain awab307,0.0
additive interaction effects working memory motor sequence training brain functional connectivity sci rep 2021 nov 29 11 1 23089 doi 101038 s41598021024929abstractalthough shared behavioral neural mechanisms working memory wm motor sequence learning msl suggested additive interactive effects training studied study aimed investigating changes brain functional connectivity fc induced sequential wm + msl msl + wm combined wm msl training programs 54 healthy subjects 27 women mean age 302 86 years allocated three training groups underwent twentyfour 40min training sessions 6 weeks four cognitive assessments including functional mri doublebaseline approach applied account practice effects test performances compared using linear mixedeffects models ttests resting state fmri data analysed using fsl processing speed verbal wm manual dexterity increased following training groups msl + wm training led additive effects processing speed verbal wm increased fc found training network including right angular gyrus left superior temporal sulcus right superior parietal gyrus bilateral middle temporal gyri left precentral gyrus difference fc found double baselines results indicate distinct patterns resting state fc modulation related sequential combined wm msl training suggesting relevance order training performance observations provide new insight planning effective training rehabilitationpmid34845312 doi101038 s41598021024929,0.0
humoral immune response covid19 vaccines people secondary progressive multiple sclerosis treated siponimod 1 introductioncompared relapsingremitting multiple sclerosis rrms secondary progressive multiple sclerosis spms characterized older age higher level disability higher occurrence cardiovascular comorbidities cree et al 2021 particular importance light covid19 pandemics realworld studies published far identified age cardiovascular comorbidities independent risk factors poor covid19 outcomes level neurological disability progressive multiple sclerosis ms phenotypes additionally increasing risk sormani et al 2021 salter et al 2021 arrambide et al 2021 data also suggest attenuated humoral response sarscov2 infection covid19 vaccination people rrms depending disease modifying therapies used habek et al 2021 achiron et al 2021 recently siponimoda sphingosine 1phosphate receptor modulatorhas approved treatment active spms ema 2021 limited data exist response vaccination people spms pwspms treated siponimod aim study determine development humoral response covid19 vaccination pwspms siponimod compared healthy controls hc 2 methodsin 13 pwspms taking siponimod 11 hc testing sarscov2 antibodies performed vaccination covid19 elecsys antisarscov2 s assay roche diagnostics int rotkreuz switzerland used per manufacturernulls instructions xxxx 2021 using cobas e 801 analytical unit immunoassay tests f hoffmannla roche ltd antibody titer 08 u ml considered positive recommended manufacturer international standard covid19 serological tests conversion factor bau ml 1288 1u ml equals 1288 bau ml infantino et al 2021 pwspms treated center treatment siponimod least 6 months received doses covid19 vaccine invited participate monthly visits clinicaladministrative visits due siponimod reimbursement hc aged sex matched healthcare workers received doses covid19 vaccine without neurological immune related conditionthe study approved ethical committee university hospital center zagreb 02 21 ag statistical analysis performed ibm spss v25 software data distribution tested kolmogorovsmirnov test differences qualitative variables tested chisquare test differences quantitative variables tested parametric independent sample ttest nonparametric mannwhitney test pvalues less 005 considered significant3 resultsdemographic characteristics vaccination status sarscov2 igg titer vaccination presented table 1 pwspms taking siponimod significantly lower titer sarscov2 antibodies compared healthy controls 194 0250 vs 250 250 p0001 figure 1 two 154 pwspms siponimod unmeasurable titers sarscov22 antibodies hc positive titers,0.0
ultrahigh field spinal cord mri multiple sclerosis standing literature review abstractmagnetic resonance imaging mri cornerstone multiple sclerosis ms diagnostics monitoring ultrahigh field uhf mri increasingly used becoming accessible due small diameter mobility spinal cord imaging structure ultrahigh fields poses additional challenges compared brain imaging review potential benefits ms field providing literature overview use uhf spinal cord mri ms research elaborate challenges faced benefits include increased signal contrasttonoise enabling higher spatial resolutions can improve ms lesion sensitivity spinal white matter well grey matter additionally benefits can aid imaging microstructural abnormalities spinal cord ms using advanced mri techniques like functional imaging mr spectroscopy diffusionbased techniques technical challenges include increased magnetic field inhomogeneities distortions physiological motion optimalisation sequences approaches including parallel imaging techniques real time shimming retrospective compensation physiological motion making increasingly possible unravel potential spinal cord uhf mri context ms research,0.0
natalizumab administration multiple sclerosis patients active sarscov2 infection case series background coronavirus disease 2019 covid19 caused new severe acute respiratory syndrome coronavirus 2 sarscov2 become pandemic affecting therapeutic management multiple sclerosis ms decision regarding discontinuation highpotency agents moderate highly active ms carefully evaluated taking account potential risk rebound disease particular data clinical outcome patients ms receiving natalizumab ntz active covid19 infection reported yetcases presentationwe reported 6 patients treated ntz relapsing ms active covid19 infection recovered without reporting worsening new symptoms patients asymptomatic exception one patient slight worst covid19 clinical course patients received o2therapy required intensive care neurological complications observedconclusionsthis paper reported clinical outcome patients ms receiving ntz active covid19 infection case series suggests treatment ntz pandemic relatively safe might continued selected patients infected covid19 thereby reducing risk ms disease rebound,0.0
evaluation shortterm safety covid19 vaccines patients multiple sclerosis latin america mult scler j exp transl clin 2021 nov 29 7 4 20552173211061543 doi 101177 20552173211061543 ecollection 2021 octabstractbackground date data available safety covid19 vaccines latin american patients multiple sclerosis ms objective characterize safety covid19 vaccines latin american latam patients multiple sclerosis pwms methods crosssectional study february 1 2021 april 30 2021 individuals ms latam countries invited participate selfadministered webbased survey ms patient organizations regionresults 393 vaccinated pwms 10 different latin american countries included vaccines administered inactivated virus vaccines ivv 382 patients adenovirus vector vaccines adv 488 mrna vaccines 13 patients received least one dose covid19 vaccines 123 313 declared receiving second dose mean sd age 415 118 years 824 female ms disease duration 84 82 years serious adverse events reported covid19 vaccines either first second dose lower frequency adverse events found ivv 22 comparison adv 464 mrna 353 p 001 five participants reported ms relapse ivv first doseconclusion covid19 vaccines applied latam proved safe ms patientspmid34868630 pmcpmc8637726 doi101177 20552173211061543,0.0
changes lymphocytes neutrophils immunoglobulins year1 cladribine treatment multiple sclerosis cladribine synthetic purine nucleoside analogue approved treatment active multiple sclerosis ms cladribine mechanismofaction encompasses selective cytotoxicity circulating autoreactive b t lymphocytes thought drive inflammatory demyelination neuroaxonal loss ms compston coles 2008 looking clinical trial results cladribine treatment marked longlasting cd19 bcell depletion rather modest tcell depletion baker et al 2017 stuve et al 2019 comi et al 2019 ideally cladribine targets memory b cells moser et al 2020 plasma cells remain unaffected jacobs et al 2018 normal immunoglobulin ig levels though never explored,1.0
potential serum neurofilament biomarker multiple sclerosis brain 2021 jun 28awab241 doi 101093 brain awab241 online ahead printabstractmultiple sclerosis highly heterogeneous disease detection neuroaxonal damage well quantification critical step patients bloodbased neurofilament light chain snfl currently close investigation easily accessible biomarker prognosis treatment response multiple sclerosis patients abundant evidence snfl levels reflect ongoing inflammatorydriven neuroaxonal damage eg relapses mri disease activity snfl levels predict disease activity next years contrast association snfl longterm clinical outcomes ability reflect slow diffuse neurodegenerative damage multiple sclerosis less clear however early results realworld cohorts clinical trials using snfl marker treatment response multiple sclerosis encouraging importantly clinical algorithms now developed incorporate routine use snfl guide individualized clinical decisionmaking people multiple sclerosis together additional fluid biomarkers clinical mri measures propose specific clinical scenarios implementing snfl measures may utility including among others initial diagnosis first treatment choice surveillance subclinical disease activity guidance therapy selectionpmid34180982 doi101093 brain awab241,0.0
intermittent hypoxia treatment alleviates memory impairment 6monthold appswe#x2f ps1de9 mice reduces amyloid beta accumulation inflammation brain background alzheimers disease ad progressive degenerative terminal disease without cure urgent need new strategy treat ad aim study investigate effects intermittent hypoxic treatment iht cognitive functions mouse model ad unravel mechanism action ihtmethodssixmonthold appswe ps1de9 app ps1 male mice exposed hypoxic environment 143 o2 4 h day 14 days 28 days cognitive functions measured morris water maze test either 14 days 42 days interval thereafter distribution amyloid plaque microglial activation determined mouse brain immunohistochemistry amyloid beta inflammatory cytokines measured elisa western blot microarray used studying gene expressions hippocampusresultsiht 14 days 28 days significantly improved spatial memory ability 6monthold app ps1 mice memory improvement 14 days iht lasted 14 days 42 days level plaques neurofilament accumulations reduced markedly iht exposure iht reduced proinflammatory cytokines il1 il6 levels secretase cleavage app processing implies reduced production microarray analysis revealed large number genes hippocampus significantly altered known metabolismregulated genesconclusionsthis study provides evidence beneficial effect iht progression ad alleviating memory impairment reducing accumulation inflammation brain iht can developed novel measure relieve progression ad targeting multiple pathways ad pathogenesis,0.0
pregnancy ms patients safe impact ms course real world evidence 1533 pregnancies czech republic abstractbackground special care ms women planning pregnancy highly demanding especially terms disease modifying treatment dmd decisions counselling regarding periods conception pregnancy postpartum periodobjective provide data impact pregnancy delivery miscarriage artificial abortion ms disease course czech women ms based analysis retrospective data czech national registry remusmethods analysis focused women ms least one record pregnancy registry clinical data edss relapses collected prior conception pregnancy delivery miscarriage artificial abortion data analysed according baseline characteristics dmd treatment prior conception according breastfeeding statusresults total 1533 pregnancies analysed period 2013 31st december 2019 occurrence relapses worse edss significantly related treatment escalation therapy prior conception relapses significantly frequent women breastfed less 3 months women breastfed 3 months breastfeed patients treated either fingolimod natalizumab prior pregnancy significantly likely develop relapses pregnancyconclusion pregnancy postpartum period generally safe czech women ms better disease outcomes observed treated first line injectable dmds prior conception either breastfed 3 months breastfeed confirmed assumption rebound phenomenon ms discontinuation treatment due planned pregnancy fingolimod natalizumab,0.0
optical coherence tomography visual evoked potential relationship neurological disability patients relapsingremitting multiple sclerosis abstractintroduction evaluate relationship retinal nerve fiber layer involvement visual evoked potential neurological disability scale relapsing remitting multiple sclerosismethods fiftytwo patients diagnosed relapsingremitting multiple sclerosis evaluated study optical coherence tomography retinal nerve fiber layer rnfl macular volume mv pattern visual evoked potential vep latency p100 wave amplitude neurological disability scale edss performed baseline evaluation carried repeated one year two yearsresults baseline values retinal nerve fiber layer 825 75935 latency amplitude vep 116 1081255 9 711 respectively edss 2 153 correlation found higher edss prolonged latency decreased amplitude p100 wave association higher edss prolongation latency p100 wave longer time evolution ms relationship found edss macular volume higher edss associated significant decrease rnfl discriminative performance disability evaluated latency vep presented area curve 079 ci95 067 092 amplitude vep area curve 071 ci95 056 087 rnfl area curve 076 95 ci 062 090 comparing rnfl mv pev eyes without previous optic neuritis rnfl values 88 8197 76 7181 p 00007 mv 246 232261 241 229251 p 02541 pev latency 109 105117 125 118129 p 00001 vep amplitude 9 710 9 711 p 09391 respectively shows statistically significant correlation decrease rnfl prolongation vep latency eyes previous optic neuritis 2year followup significant differences values rnfl vep edssdiscussion study relationship evidenced retinal nerve fiber thickness pev degree disability measured edss patients relapsing ms remissions baseline values lower rnfl thickness correlated prolonged latency decreased amplitude pev associated higher edss relationship significant eyes previous optic neuritis terms decreased rnfl thickness prolongation pev latency significant differences found 2year followup measurements made,0.0
microrna1005p microrna2985p released apoptotic cortical neurons endogenous tolllike receptor 7#x2f 8 ligands contribute neurodegeneration background microrna mirna expression brain altered neurodegenerative diseases recent studies demonstrated selected mirnas conventionally regulating gene expression posttranscriptional level can act extracellularly signaling molecules identity mirna species serving membrane receptor ligands involved neuronal apoptosis central nervous system cns well mirnas sequence structure required mode action remained largely unresolvedmethodsusing microarraybased screening approach analyzed apoptotic cortical neurons c56bl 6 mice supernatant respect alterations mirna expression presence hekblue tolllike receptor tlr 7 8 reporter cells primary microglia macrophages derived human mouse employed test potential identified mirnas released apoptotic neurons serve signaling molecules rnasensing receptors biophysical bioinformatical approaches well immunoassays sequential microscopy used analyze interaction candidate mirna tlr immunocytochemical histochemical analyses murine cns cultures adult mice intrathecally injected mirnas respectively performed evaluate impact mirnainduced tlr activation neuronal survival microglial activationresultswe identified specific pattern mirnas released apoptotic cortical neurons activate tlr7 tlr8 depending sequence species exposure microglia macrophages certain mirna classes released apoptotic neurons resulted sequencespecific production distinct cytokines chemokines increased phagocytic activity mirnas mir1005p mir2985p consistently linked neurodegenerative diseases entered microglia located endosomes directly bound human tlr8 mirnatlr interaction required novel sequence features specific structure formation mature mirna consequence mir1005p mir2985pinduced tlr activation cortical neurons underwent cellautonomous apoptosis presence mir1005p mir2985p cerebrospinal fluid led neurodegeneration microglial accumulation murine cerebral cortex tlr7 signalingconclusionour data demonstrate specific mirnas released apoptotic cortical neurons serve endogenous tlr7 8 ligands thereby trigger neuronal apoptosis cns findings underline recently discovered role mirnas extracellular signaling molecules particularly context neurodegeneration,0.0
comprehensive approach stool donor screening faecal microbiota transplantation china background faecal microbiota transplantation fmt effective therapy recurrent clostridium difficile infections chronic gastrointestional infections however risks fmt selection process suitable donors remain insufficiently characterized eligibility rate screening underlying microbial basis core ethical issues stool donors fmt yet elucidated chinaresultsthe potential stool donors screened december 2017 december 2019 help online survey clinical assessments stool blood testing bioinformatics analyses performed composition stability gut microbiota stool obtained eligible donors dynamically observed using metagenomics meanwhile build donor microbial evaluation index domei stool donor screening screening process also focused ethical principles requirements 2071 participants 66 donors selected via screening process 319 success rate although significant differences gut microbiota among donors found changes gut microbiota donor typically stable donors timeconclusionsdomei provides potential reference index regular stool donor reevaluation retrospective study summarised donor recruitment screening procedure ensuring safety tolerability fmt china based latest advances field carried rigorous recommendation method can assist stool bank clinicians screen eligible stool donor fmt,0.0
scleroderma patientcentered intervention network selfmanagement spinself program protocol twoarm parallel partially nested randomized controlled feasibility trial progression fullscale trial background systemic sclerosis scleroderma ssc rare autoimmune connective tissue disease completed initial feasibility trial online selfadministered version scleroderma patientcentered intervention network selfmanagement spinself program using cohort multiple randomized controlled trial rct design due low intervention offer uptake will conduct new feasibility trial progression fullscale trial using twoarm parallel partially nested rct design spinself program also revised include facilitatorled videoconference group sessions addition online material will test groupbased intervention delivery format evaluate effect spinself program disease management selfefficacy primary patient activation social appearance anxiety functional health outcomes secondary methodsthis study feasibility trial progression fullscale rct pending meeting predefined criteria spinself program participants will recruited ongoing spin cohort http wwwspinsclerocom en cohort via social media partner patient organizations eligible participants must ssc low moderate disease management selfefficacy selfefficacy managing chronic disease semcd scale score 70 participants will randomized 11 allocation groupbased spinself program usual care 3 months primary outcome fullscale trial will disease management selfefficacy based semcd scale scores 3 months postrandomization secondary outcomes include semcd scores 6 months postrandomization plus patient activation social appearance anxiety functional health outcomes 3 6 months postrandomization will include 40 participants assess feasibility end feasibility portion stoppage criteria will used determine trial procedures spinself program need important modifications thereby requiring reset fullscale trial otherwise fullscale rct will proceed outcome data feasibility portion will utilized fullscale trial fullscale rct 524 participants will recruiteddiscussionthe spinself program may improve disease management selfefficacy patient activation social appearance anxiety functional health outcomes people ssc spin works partner patient organizations around world disseminate programs freeofchargetrial registrationclinicaltrialsgovnct04246528 registered 27 january 2020,0.0
case report unexpected origin coma young adult abstractwe report peculiar case acute nontraumatic coma due neuromuscular hypoventilation syndrome caused nontraumatic spinal cord injury ntsci 21yearold patient presented emergency room complaining sudden onset weakness lower limbs shortness breath er briefly became comatose labs revealed acute respiratory acidosis detailed neurologic examination ultimately revealed upper motor neuron signs quadriplegia ultimately diagnosed nontraumatic spinal cord injury particular cervical transverse myelitis caused acute diaphragmatic weakness although rare cause coma emergency medicine physicians need aware transverse myelitis disorder may result rapidly progressive neurologic decline treated immunomodulation,0.0
dysregulated phosphoinositide 3kinase signaling microglia shaping chronic neuroinflammation abstractmicroglia integral mediators innate immunity within mammalian central nervous system typical microglial responses transient intending restore homeostasis orchestrating removal pathogens debris regeneration damaged neurons however prolonged persistent microglial activation can drive chronic neuroinflammation associated neurodegenerative disease recent evidence revealed abnormalities microglial signaling pathways involving phosphatidylinositol 3kinase pi3k protein kinase b akt may contribute altered microglial activity exacerbated neuroimmune responses scoping review known suspected roles pi3kakt signaling microglia health pathological states will examined key microglial receptors induce pi3kakt signaling microglia will described since aberrant signaling correlated neurodegenerative disease onset relationship maladapted pi3kakt signaling development neurodegenerative disease will also explored finally studies microglial pi3kakt signaling modulated will highlighted may prove promising therapeutic approach future treatment range neuroinflammatory conditions,0.0
exploring impact ineligibility individuals expressing interest trial aimed improving daily functioning regarding perceptions self research likelihood future participation background eligibility guidelines research trials necessary minimise confounds reduce bias interpretation potential treatment effects limited extant research investigating deemed ineligible trials might impact patients perceptions research better understanding impact patient ineligibility enhance design implementation future research studiesmethodseight semistructured telephone interviews conducted explore impact ineligibility selfperceptions perceptions regarding nature research likelihood expressing interest future research data collected analysed thematically inductive interpretive phenomenological analysis ipa resultsfive themes emerged regarding experience deemed ineligible 1 deemed ineligible emotion reaction evoking 2 bit helping others increasing value research 3 communication ineligibility 4 appreciation express interest 5 subsequent perceptions attitudes towards researchconclusionsthe results suggest deemed ineligible can elicit negative emotional outcomes likely change perceptions attitudes towards research possibly due desire help similar others ineligibility can impact future participation cases thus reducing recruitment pool subsequent research studies recommendations provided help minimise risk advising ineligibility personal way recommended enhanced clarity regarding reasoning behind decision providing opportunities ask questions ensuring appreciation patients time interest communicated,0.0
interferoninduced sarcoidosis uveitis initial symptom case report review theliterature background recent years numerous studies reported development exacerbation sarcoidosis due interferon therapy however ocular lesions rarely present initial symptoms herein describe rare case interferoninduced sarcoidosis uveitis initial symptom present review relevant literaturecase presentationthis case involved 62yearoldjapanese woman history combination treatment pegylated interferon2a ribavirin simeprevir developed granulomatous panuveitis subsequently diagnosed sarcoidosis following histological examination skin biopsy specimens addition reporting case performed literature review 27 cases 24 case reports histopathologically diagnosed interferoninduced sarcoidosis published january 2009 november 2018conclusionsamong reviewed cases 23 851 cases developed skin lesions 19 701 lung lesions three cases 111 accompanying eye lesions interferon therapy discontinued 16 cases 529 majority exhibited improvement systemic corticosteroid treatment reported cases interferoninduced sarcoidosis uveitis initial symptom however uveitis develops interferon treatment might represent initial symptom interferoninduced sarcoidosis observed present case,0.0
pentafluorosulfanyl sf5 superior 19f magnetic resonance reporter group signal detection biological activity teriflunomide derivatives acs sens 2021 oct 19 doi 101021 acssensors1c01024 online ahead printabstractfluorine 19f magnetic resonance imaging mri severely limited low signalto noise ratio snr tapping 19f drug detection vivo still poses significant challenge however bears potential labelfree theranostic imaging recently detected fluorinated dihydroorotate dehydrogenase dhodh inhibitor teriflunomide tf noninvasively animal model multiple sclerosis ms using 19f mr spectroscopy mrs present study probed distinct modifications cf3 group tf improve snr revealed sf5 superior alternative cf3 group value sf5 bioisostere 19f mri reporter group within biological pharmacological context far underexplored compared biological pharmacological activities different tf derivatives 19f mr properties chemical shift relaxation times 19f mr snr efficiency three mri methods revealed sf5substituted tf highest 19f mr snr efficiency combination ultrashort echotime ute mri method chemical modifications reduce pharmacological biological activity shown vitro dihydroorotate dehydrogenase enzyme t cell proliferation assays instead sf5substituted tf showed improved capacity inhibit t cell proliferation indicating better antiinflammatory activity suitability viable bioisostere context study proposes sf5 novel superior 19f mr reporter group ms drug teriflunomidepmid34666481 doi101021 acssensors1c01024,0.0
diagnostic value aquaporin4igg live cell based assay neuromyelitis optica spectrum disorders mult scler j exp transl clin 2021 nov 26 7 4 20552173211052656 doi 101177 20552173211052656 ecollection 2021 octabstractobjective determine utility aquaporin 4 igg aqp4igg testing live cellbased assay neuromyelitis optica spectrum disorders nmosd methods included mayo clinic patients 1 1 201812 31 2019 tested serum aqp4igg live cellbased flowcytometric assay medical records reviewed assess patients fulfilled 2015 nmosd criteriaresults 1371 patients tested 41 positive 3 fulfilled nmosd criteria aqp4igg specificity 100 10 1330 testing negative met nmosd criteria without aqp4igg sensitivity 80 seven 10 mogigg positiveconclusions aqp4igg live cellbased assay highly specific without false positives high throughput settingpmid34868626 pmcpmc8637716 doi101177 20552173211052656,0.0
new epidermalgrowthfactorrelated insights pathogenesis multiple sclerosis also epistemology front neurol 2021 nov 26 12754270 doi 103389 fneur2021754270 ecollection 2021abstractrecent findings showing epidermal growth factor egf significantly decreased cerebrospinal fluid csf spinal cord sc living deceased multiple sclerosis ms patients repeated administration rodents chemically virallyinduced demyelination central nervous system cns experimental allergic encephalomyelitis eae prevents demyelination inflammatory reactions cns led critical reassessment ms pathogenesis partly egf considered little role immunology egf myelinotrophic factor tested csf spinal cord ms patients shown good correspondence liquid tissue levels review briefly summarises positive egf effects neural stem cells oligodendrocyte cell lineage astrocytes order explain least part biological basis myelin loss remyelination failure ms b short analysis evolution principle causeeffect history western philosophy highlights lack experimental immune toxin virusmediated model precisely reproduces histopathological features clinical symptoms ms thus underlining inapplicability claude bernards crucial sequence observation hypothesis hypothesis testing followed discussion putative nonimmunologicallylinked points ms pathogenesis abnormalities myelinotrophic factor csf levels oligodendrocytes odcs astrocytes extracellular matrix epigenetics basis poppers falsification principle suggestion autoimmunity phologosis reactions surely devasting consequences disease probably last links chain events trigger reactions likely lack myelinotrophic growth factors myelinogenesis controlled various cns extracns growth factors molecules within outside odcs studies needed investigate role nonimmunological molecules time onset disease words galilei human mind prepared understand nature createdpmid34899572 pmcpmc8664554 doi103389 fneur2021754270,1.0
differential role p53 oligodendrocyte survival response various stresses experimental autoimmune encephalomyelitis cuprizone intoxication white matter stroke int j mol sci 2021 nov 26 22 23 12811 doi 103390 ijms222312811abstractpromoting oligodendrocyte viability proposed therapeutic strategy alleviating many neuronal diseases multiple sclerosis stroke however molecular pathways critical oligodendrocyte survival various stresses still well known p53 strong tumor suppressor regulates cell cycle dna repair cell death previous studies shown p53 plays important role promoting neuronal survival insults specific role oligodendrocyte survival known constructed mice oligodendrocytespecific p53 loss crossing trp53flox flox mice cnpcre mice found p53 dispensable oligodendrocyte differentiation myelin formation physiological condition experimental autoimmune encephalomyelitis eae model p53 loss function specifically oligodendrocytes affect eae disease severity effect demyelination spinal cord mice interestingly p53 deficiency oligodendrocytes significantly attenuated demyelination corpus callosum alleviated functional impairment motor coordination spatial memory cuprizone demyelination model moreover oligodendrocytespecific loss p53 provided protection subcortical white matter damage mitigated recognition memory impairment mice white matter stroke model results suggest p53 plays different roles brain spinal cord response various stresses thus p53 may therapeutic target oligodendrocyte prevention specific brain injuries white matter stroke multiple sclerosispmid34884611 doi103390 ijms222312811,1.0
microwellbased impedance sensor insertable microneedle realtime vivo cytokine detection microsyst nanoeng 2021 nov 26 796 doi 101038 s41378021002974 ecollection 2021abstractimpedancebased protein detection sensors pointofcare diagnostics require quantitative specificity well rapid realtime operation furthermore microfabrication sensors can lead formation factors suitable vivo operation herein present microfabricated needleshaped microwell impedance sensors rapidsampletoanswer labelfree detection cytokines biomarkers microneedle form factor allows sensors utilized transcutaneous transvascular sensing applications vitro experimental characterization confirmed sensor specificity sensitivity multiple proteins interest mechanical characterization demonstrated sufficient microneedle robustness transcutaneous insertion well preserved sensor function postinsertion utilized sensors carry realtime vivo quantification human interleukin 8 hil8 concentration levels blood transgenic mice endogenously express hil8 assess sensor functionality hil8 concentration levels serum samples mice quantified elisa excellent agreement realtime vivo sensor readings blood subsequent elisa serum assays observed multiple transgenic mice expressing hil8 concentrations 62 pg ml 539 ng mlpmid34900330 pmcpmc8626445 doi101038 s41378021002974,0.0
effects braincomputer interface functional electrical stimulation gait rehabilitation multiple sclerosis patients preliminary findings gait speed eventrelated desynchronization onset latency j neural eng 2021 nov 15 doi 101088 17412552 ac39b8 online ahead printabstractobjective braincomputer interfaces bci functional electrical stimulation fes feedback device might promote neuroplasticity hence improve motor function novel findings suggested neuroplasticity possible people multiple sclerosis pwms preliminary study explores effects using bcifes therapeutic intervention emerging methodology gait rehabilitation pwmsapproach people relapsingremitting primary progressive secondary progressive ms evaluated inclusion criteria enroll 9 participants required statistically computed sample size patient trained bcifes 24 sessions distributed 8 weeks effects evaluated gait speed timed 25 foot walk walking ability 12item multiple sclerosis walking scale quality life measures true positive rate bcifes performance metric eventrelated desynchronization onset latency sensorimotor rhythmsmain results seven patients completed therapeutic intervention statistically clinically significant posttreatment improvement observed gait speed result reduction time walk 25 feet 199 s p0018 walking ability 3125 score points p0028 true positive rate showed statistically significant improvement +1587 score points p0018 earlier eventrelated desynchronization onset latency 180ms treatment foundsignificance first study explored gait rehabilitation using bcifes pwms results showed improvement gait might promoted changes functional brain connections involved sensorimotor rhythm modulation although studies larger sample size control group required validate efficacy approach results suggest bcifes technology positive effect ms gait rehabilitationpmid34781272 doi101088 17412552 ac39b8,0.0
identification validation tumor microenvironmentrelated gene signature hepatocellular carcinoma prognosis front genet 2021 nov 26 12717319 doi 103389 fgene2021717319 ecollection 2021abstractbackground hepatocellular carcinoma hcc typical inflammatoryrelated malignant tumor complex immune tolerance microenvironment poor prognosis study aimed construct novel immunerelated gene signature prognosis hcc patients exploring tumor microenvironment tme cell infiltration characterization potential mechanisms methods total 364 hcc samples followup information tcgalihc dataset analyzed training prognostic signature least absolute shrinkage selector operation lasso regression based irgs conducted identify prognostic genes establish immune risk signature immune cell infiltration tme estimated via cibersort method gene set variation analysis gsva conducted compare biological pathways involved lowrisk highrisk groups furthermore paraffin sections hcc tissue microarrays containing 77 patients fudan university shanghai cancer center used ihc staining clinical characteristics 77 hcc patients collected summarized survival analysis validation via kaplanmeier km method results threegene signature close immune correlation risk score epo 002838 + birc5 002477 + spp1 00002044 constructed eventually proven effective prognostic factor hcc patients patients divided highrisk lowrisk group according optimal cutoff survival analysis revealed hcc samples highrisk immunoscore significantly poorer outcomes lowrisk group p 00001 results cibersort suggested immune cell activation relatively higher lowrisk group better prognosis besides gsva analysis showed multiple signaling differences high lowrisk group indicating threegene prognostic model can affect prognosis patients affecting immunerelated mechanisms tissue microarray tma results confirmed expression three genes hcc tissues closely related prognosis patients respectively conclusion study constructed validated robust threegene signature close immune correlation hcc presented reliable performance prediction hcc patients survivalpmid34899826 pmcpmc8662347 doi103389 fgene2021717319,0.0
diagnostic value gadolinium contrast administration spinal cord magnetic resonance imaging multiple sclerosis patients correlative markers lesion enhancement mult scler j exp transl clin 2021 nov 26 7 4 20552173211047978 doi 101177 20552173211047978 ecollection 2021 octabstractbackground magnetic resonance imaging essential monitoring people multiple sclerosis diagnostic value gadolinium contrast administration spine magnetic resonance imaging unclearobjective assess diagnostic value gadolinium contrast administration spine magnetic resonance imaging followup examinations identify imaging markers correlating lesion enhancementmethods total 65 multiple sclerosis patients least 2 spinal magnetic resonance imaging followup examinations included spine magnetic resonance imaging performed 3 tesla standardized protocol sagittal axial t2weighted turbo spin echo t1weighted postcontrast sequences t2 lesion load enhancing lesions assessed two independent neuroradiologists lesion size localization t2 signal ratio t2 signallesion t2 signalnormal appearing spinal cord results total 68 new spinal t2 lesions 20 new contrastenhancing lesions developed followup enhancing lesions discernable correlate new t2 lesion lesion enhancement correlated higher t2 signal ratio compared nonenhancing lesions t2 signal ratio 20 04 vs 14 02 p 0001 receiver operating characteristics analysis showed optimal cutoff value signal ratio 178 predict lesion enhancement 82 sensitivity 97 specificity conclusion gadolinium contrast administration dispensable followup spine magnetic resonance imaging new t2 lesions present probability enhancement correlates t2 signal ratiopmid34868625 pmcpmc8637714 doi101177 20552173211047978,0.0
metformin attenuates lpsinduced neuronal injury cognitive impairments blocking nfb pathway background neuroinflammatory response considered highrisk factor cognitive impairments brain lipopolysaccharides lps endotoxin induces acute inflammatory responses injected bodies however molecular mechanisms underlying lpsassociated cognitive impairments still remain unclearmethodshere primary hippocampal neurons treated lps western blotting immunofluorescence used investigate whether lps induces neurons damage time sd rats injected lps 830 g kg intraperitoneally open field test novel objective recognition test fear condition test used detect cognitive function ltp used assess synaptic plasticity molecular biology technology used assess nfb pathway elisa used detect inflammatory factors addition metformin used treat primary hippocampal neurons intraventricularly administered sd rats molecular technics behavioral electrophysiological tests used examine whether metformin alleviate lpsassociated neuronal damage well synaptic plasticity behavioral alterations sd ratsresultsaltogether neuronal damage observed primary hippocampal neurons lps intervention alleviated metformin treatment time lps injection rat triggers cognitive impairment activation nfb signaling pathway metformin administration alleviates lpsinduced memory dysfunction improves synaptic plasticityconclusionthese findings highlight novel pathogenic mechanism lpsrelated cognitive impairments activation nfb signaling pathway accumulation inflammatory mediators induces neuronal pathologic changes cognitive impairments however metformin attenuates lpsinduced neuronal injury cognitive impairments blocking nfb pathway,0.0
tetracyclines diminish vitro ifngamma il17producing adaptive innate immune cells multiple sclerosis front immunol 2021 nov 26 12739186 doi 103389 fimmu2021739186 ecollection 2021abstractintroduction limited data clinical trials multiple sclerosis ms reported minocycline widely used antibiotic belonging family tetracyclines tcs exerts beneficial shortlived clinical effect similar antiinflammatory effect minocycline attributed deviation th1 th2 immune response reported experimental models ms whether immunomodulatory mechanism operated human disease remains largely unknownaim assess vitro immunomodulatory effect tetracyclines particular minocycline doxycycline nave treated patients msmaterial methods peripheral blood mononuclear cells 45 individuals 35 ms patients amongst 15 nave patients 10 healthy controls hcs cultured minocycline doxycycline conventional stimulants pma ionomycin il12 il18 ifn il17 producing t nk nkt cells assessed flow cytometry effect tcs cell viability apoptosis assessed flow cytometry annexin v stainingresults tetracyclines significantly decreased dose dependent manner ifn production nkt cd4+ t lymphocytes ms patients nave treated stimulated il12 il18 decrease ifn producing cd8+ t cells naive ms treated rrms patients also decreased il17+ t nkt cells following pma ionomycinstimulation tetracyclines affect viability cell subsetsconclusion tetracyclines can vitro suppress ifn il17 producing cells ms patients may explain potential therapeutic effect vivopmid34899697 pmcpmc8662812 doi103389 fimmu2021739186,0.0
diffusely abnormal white matter clinically isolated syndrome associated parenchymal loss elevated neurofilament levels summarywe characterized frequency diffusely abnormal white matter dawm across broad spectrum multiple sclerosis ms participants 35 clinically isolated syndrome cis 57 relapsing remitting 64 secondary progressive ms participants demonstrated dawm cis dawm decreased cortical thickness higher lesion load higher concentration serum neurofilament light chain compared cis without dawm dawm may useful identifying cis patients greater injury brains larger longitudinal studies warranted,0.0
two weeks twicedaily prism adaptation treatment improve posture gait parkinsons disease doubleblind randomized controlled trial background gait difficulties parkinsons disease related problems shifting center gravity forward previously showed reduced forward stepping latencies people parkinsons disease one session adaptation upward visual shifts produces downward motor aftereffects potentially shifts center gravity forward tested repeated prism adaptation improved gait postural control parkinsons disease parallel doubleblind randomized shamcontrolled trialmethodswe recruited participants idiopathic parkinsons disease aged 4085 meeting one three clinical criteria 1 hoehn yahr stage ii5iv 2 scoring 0 gait freezing gait postural stability items movement disorder society unified parkinsons disease rating scale 3 timed go 12 s sealed envelope style randomization allocated participants two weeks twicedaily prism adaptation sham treatment participants care givers assessing outcomes blinded group assignment primary outcomes changes postural control measured using berg balance scale limits stability sensory organization motor control tests smart equitest system secondary outcomes included physiotherapy questionnaire measures outcomes assessed dartmouth hitchcock medical center immediately treatment period longterm postal followup 3 months outcomes analyzed using analyses variance followup t testsresultseighteen participants allocated undergo prism adaptation sixteen analyzed thirteen participants allocated undergo sham treatment analyzed prism adaptation group showed increased forward stepping velocity limits stability test pre m233 sem024 post m288 sem026 t 15 32 p005 d819 sham group showed change pre m213 sem022 1d post m224 sem022 t 13 636 p537 d176 however group differences outcome measures indications prism adaptation produced functional improvements posture gait activities daily livingconclusionsprism adaptation improve gait postural control parkinsons diseasetrial registrationclinicaltrialsgovnct02380859 registered prospectively 5 march 2015,0.0
characteristics mucosalassociated invariant t cells roles immune diseases int immunol 2021 sep 11dxab070 doi 101093 intimm dxab070 online ahead printabstractmucosalassociated invariant t mait cells subset innatelike t cells express semiinvariant t cell receptor restricted molecule major histocompatibility complex class irelated molecule 1 mr1 mait cells recognize biosynthetic derivatives riboflavin synthesis pathway present microbes mait cells attracted increased interest related various immune responses unique features including abundance humans nonpeptidic antigens ability respond antigenic nonantigenic stimuli numbers circulating mait cells decreased many immune diseases multiple sclerosis systemic lupus erythematosus inflammatory bowel diseases however remaining mait cells increased cytokineproducing capacity activated status related disease activity additionally mait cells observed sites inflammation including kidneys synovial fluid intestinal mucosa findings suggest involvement pathogenesis immune diseases minireview summarize recent findings mait cells human immune diseases animal models discuss role potential therapeutic targetpmid34508634 doi101093 intimm dxab070,0.0
trend analysis palliative care consultation service terminally ill noncancer patients taiwan 9year observational study background searly integration palliative care terminally ill noncancer patients improves quality life however scanty data palliative care consultation service pccs among noncancer patientsmethodsin 9year observational study data collected hospicepalliative clinical database hpcd taichung veterans general hospital tcvgh terminally ill noncancer patients 9 categories diagnoses received pccs 2011 2019 enrolled trend analysis performed evaluate differences categories diagnosis throughout study period duration pccs patient outcomes dnr declaration awareness disease patients families pccsresultsin total 536 noncancer patients received pccs 2011 2019 average age 707 years average duration pccs 184 days distributions age gender patient outcomes familys awareness disease pccs patients awareness disease pccs significantly different among diagnoses organic brain disease chronic kidney disease ckd prevalent diagnoses patients receiving pccs 2019 dnr declaration percentage patients signing dnr pccs remained high throughout study period 928 2019 patient outcomes varied according disease diagnosesconclusionthis 9year observational study showed trend pccs among noncancer patients changed duration study increasing number terminally ill noncancer patients received pccs late life thereby increasing awareness disease patients families tend better prepare terminally ill patients endoflife may consider dnr consent early integration pccs ordinary care terminally noncancer patients essential better quality life,0.0
optimise ms study protocol pragmatic prospective observational study address need challenges real world pharmacovigilance multiple sclerosis bmj open 2021 nov 25 11 11 e050176 doi 101136 bmjopen2021050176abstractintroduction power real world data improve understanding clinical aspects multiple sclerosis ms starting realised disease modifying therapy dmt use across uk driven national prescribing guidelines uk provides ideal country gather ms outcomes data rigorously conducted observational study focus pharmacovigilance potential provide important data inform clinicians patients testing reliability estimates pivotal trials applied patients ukmethods analysis primary aim study characterise incidence compare risk serious adverse events people ms treated dmts optimisems database enables electronic data capture secure data transfer selected clinical data clinical histories patientreported outcomes collected harmonised fashion across sites time routine clinical visits first patient recruited study 24 may 2019 january 2021 1615 individuals baseline data recorded followup data captured will reported due courseethics dissemination study ethical permission london city east ref 19 lo 0064 potential concerns around data storage sharing mitigated separation identifiable data clinical data limiting access identifiable data results study will disseminated via publication participants provide consent anonymised data shared research use enhancing value studypmid34824113 doi101136 bmjopen2021050176,0.0
therapeutic immunoglobulin antibody dysbiosisrelated diseases int immunol 2021 sep 7dxab066 doi 101093 intimm dxab066 online ahead printabstractdysbiosis alterations microbial composition compared healthy microbiota often features reduction gut microbial diversity change microbial taxa dysbiosis especially gut also proposed play crucial role pathogenesis wide variety diseases including inflammatory bowel disease colorectal cancer cardiovascular disease obesity diabetes multiple sclerosis body evidence shown intestinal polymeric immunoglobulin iga antibodies important regulate gut microbiota well exclude pathogenic bacteria viral infection influenza sarscov2 severe acute respiratory syndrome coronavirus 2 mucosal sites since 1970s trials oral administration therapeutic iga igg performed mainly treat infectious enteritis caused pathogenic escherichia coli clostridium difficile however successfully developed clinical application now addition protective function intestinal pathogens iga well known modulate gut commensal microbiota leading symbiosis nevertheless development therapeutic iga drugs treat dysbiosis progressing review advantages therapeutic iga antibodies problems development will discussedpmid34492105 doi101093 intimm dxab066,0.0
early upregulation cytosolic phospholipase a2 motor neurons induced misfolded sod1 mouse model amyotrophic lateral sclerosis background amyotrophic lateral sclerosis als fatal multifactorial neurodegenerative disease characterized selective death motor neurons cytosolic phospholipase a2 alpha cpla2 upregulation activation spinal cord als patients reported previously shown cpla2 upregulation spinal cord mutant sod1 transgenic mice sod1g93a detected long development disease inhibition cpla2 upregulation delayed diseases onset aim present study determine mechanism cpla2 upregulationmethodsimmunofluorescence analysis western blot analysis misfolded sod1 cpla2 inflammatory markers performed spinal cord sections sod1g93a transgenic mice primary motor neurons expression mutant sod1 performed induction transfection primary motor neurons differentiated nsc34 motor neuron like cells resultsmisfolded sod1 detected spinal cord 3 weeks old mutant sod1g93a mice cpla2 upregulation elevated expression misfolded sod1 cpla2 specifically detected motor neurons 6 weeks high correlation elevated tnf levels detected spinal cord lysates 6 weeks old mutant sod1g93a mice elevated tnf specifically detected motor neurons expression highly correlated cpla2 expression 6 weeks induction mutant sod1 primary motor neurons induced cpla2 tnf upregulation expression mutant sod1 nsc34 cells caused cpla2 upregulation prevented antibodies tnf addition tnf nsc34 cells caused cpla2 upregulation dose dependent mannerconclusionsmotor neurons expressing elevated cpla2 tnf inflammatory state early 6 weeks old mutant sod1g93a mice long development disease accumulated misfolded sod1 motor neurons induced cpla2 upregulation via induction tnf,0.0
genomic architecture competitive response arabidopsis thaliana highly flexible among plurispecific neighborhoods front plant sci 2021 nov 25 12741122 doi 103389 fpls2021741122 ecollection 2021abstractplants daily challenged multiple abiotic biotic stresses major biotic constraint corresponds competition plant species although plants simultaneously interact multiple neighboring species throughout life cycle still limited information genetics competitive response context plurispecific interactions using local mapping population arabidopsis thaliana set genome wide association study gwas estimate extent genetic variation competitive response 12 plant species assemblages based three competitor species poa annua stellaria media veronica arvensis based five phenotypic traits detected strong crossing reaction norms three bispecific neighborhoods also among plurispecific neighborhoods genetic architecture competitive response highly dependent identity relative abundance neighboring species addition enriched biological processes underlying competitive responses largely differ among neighborhoods rna related processes might confer broad range response toolkit multiple traits diverse neighborhoods processes signaling transport might play specific role particular assemblages altogether results suggest plants can integrate respond different species assemblages depending identity number neighboring species large range candidate genes associated diverse unexpected processes leading developmental stress responsespmid34899774 pmcpmc8656689 doi103389 fpls2021741122,0.0
multisite randomized controlled trial two group education programs fatigue multiple sclerosis long term 56 year followup one site mult scler j exp transl clin 2021 nov 25 7 4 20552173211054454 doi 101177 20552173211054454 ecollection 2021 octabstractbackground multicomponent group ms fatigue selfmanagement program reduced fatigue impact compared rigorous control 12 months enrollmentobjectives assess compare changes groups fatigue impact behavior changes implemented 56 years enrollmentmethods modified fatigue impact scale mfis behavior change questionnaire administered 56 years enrollmentresults significant changes mean mfis scores within groups baseline 56 years later behavior changes similar frequency groupsconclusion fatigue impact stable behavior changes similar groups 56 years fatigue selfmanagement programpmid34868627 pmcpmc8637710 doi101177 20552173211054454,0.0
intestinal flora neurological disorders sheng wu gong cheng xue bao 2021 nov 25 37 11 37573780 doi 1013345 jcjb210253abstractthe human intestinal flora highly diverse ecosystem composed trillions bacteria imbalance flora related variety diseases intestinal flora interacts nervous system bidirectionally many ways gutbrain axis causes neuroimmune inflammatory response dysfunction gut mucosa bloodbrain barrier direct stimulation vagus nerve spinal nerve enteric nervous system neuroendocrine hypothalamuspituitaryadrenal axis causing neurological disorders metabolites intestinal microbial community also play role article summarizes characteristics altered intestinal flora intervention measures autism spectrum disorder multiple sclerosis parkinsons disease epilepsy guillainbarr syndrome alzheimers disease neuromyelitis optica hepatic encephalopathy amyotrophic lateral sclerosis schizophrenia depression chronic fatigue syndrome huntingtons disease stroke current research intestinal flora still infancy studies carried causality underlying mechanisms prevents development precise florabased clinical intervention measures expected research intestinal flora lead novel approaches treatment neurological disorderspmid34841782 doi1013345 jcjb210253,0.0
lysine acetylation proteome renal tubular epithelial cells diabetic nephropathy front genet 2021 nov 25 12767135 doi 103389 fgene2021767135 ecollection 2021abstractdiabetic nephropathy considered one common microvascular complications diabetes pathophysiology involves multiple factors progressive diabetic nephropathy believed related structure function tubular epithelial cells kidney however role lysine acetylation lesions renal tubular epithelial cells arising hyperglycemia poorly understood consequently study cultured mouse renal tubular epithelial cells vitro high glucose conditions analyzed acetylation levels proteins liquid chromatographyhighresolution mass spectrometry identified 48 upregulated proteins downregulated 86 proteins addition identified 113 sites higher acetylation levels 374 sites lower acetylation levels subcellular localization analysis showed majority acetylated proteins located mitochondria 4317 nucleus 2857 cytoplasm 1619 enrichment analysis indicated acetylated proteins primarily associated oxidative phosphorylation citrate cycle tca cycle metabolic pathways carbon metabolism addition used mcode plugin cytohubba plugin cytoscape software analyze ppi network displayed first four compact mocdes top 10 hub genes differentially expressed proteins global acetylated proteomes finally extracted 37 conserved motifs 4915 acetylated peptides collectively comprehensive analysis proteome reveals novel insights role lysine acetylation tubular epithelial cells may make valuable contribution towards identification pathological mechanisms diabetic nephropathypmid34899851 pmcpmc8657754 doi103389 fgene2021767135,0.0
national representative crosssectional study hellenic academy neuroimmunology helani covid19 multiple sclerosis overall impact willingness toward vaccination front neurol 2021 nov 25 12757038 doi 103389 fneur2021757038 ecollection 2021abstractbackground context coronavirus disease 2019 covid19 pandemic constant needs people multiple sclerosis pwms caregivers urgently highlighted aim present study aims capture effects covid19 pandemic several aspects quality life pwms perception behavior covid19 multiple sclerosis ms well concerning healthcare working conditions willingness toward covid19 vaccination methods study initiative hellenic academy neuroimmunology helani included ms data alliance msda catalog can accessed creating account https msdaemifcatalogueeu login two online questionnaires administered impact covid19 pandemic quality life behavior healthcare pwms questionnaire ii vaccination covid19 questionnaire b people ms invited participate hellenic federation persons multiple sclerosis hfopwms results threehundredninety pwms responded questionnaire whereas 176 pwms provided answers questionnaire b older age longer disease duration higher msrelated disability associated increased perceived sensitivity toward severe acute respiratory syndrome coronavirus 2 sarscov2 infection well increased perceived severity covid19 upon potential infection significant proportion pwms experienced restricted access msrelated health professionals diseasemodifying therapy dmt prescription msrelated laboratory examination due pandemic subgroups pwms reported exacerbated symptoms ie chronic msrelated symptoms fatigue worsening preexisting fatigue sexual dysfunction worsening preexisting sexual dysfunction overall majority participants reported either strong willingness get vaccinated covid19 likeliness undergo vaccination aware helani recommendations regarding covid19 vaccination pwms reported increase willingness participants receive vaccine conclusions results highlight necessity scientific patient organizations taking joint action increase awareness healthrelated issues pandemic provide accurate uptodate guidance pwms online information communications technology ict tools polling public belief behavior may prove valuable means retaining active routes communication stakeholderspmid34899577 pmcpmc8656423 doi103389 fneur2021757038,0.0
role tgf bmpr2 signaling pathwayrelated mirna pulmonary arterial hypertension systemic sclerosis abstractpulmonary arterial hypertension pah severe complication connective tissue disease ctd causing death systemic sclerosis ssc past decade yielded many scientific insights microrna mirnas pah ssc growth knowledge wellillustrated complexity microrna mirna based regulation gene expression pah however mirnarelated sscpah elucidated review firstly discusses role transforming growth factorbeta tgf signaling bone morphogenetic protein receptor type ii bmpr2 pah ssc secondly mirnas relating tgf bmpr2 signaling pathways pah ssc merely pah subsequently summarized finally future studies might develop early diagnostic biomarkers targetoriented therapeutic strategies sscpah pah treatment,0.0
assessing lumbar plexus sciatic nerve damage relapsingremitting multiple sclerosis using magnetisation transfer ratio front neurol 2021 nov 25 12763143 doi 103389 fneur2021763143 ecollection 2021abstractbackground multiple sclerosis ms traditionally regarded disease confined central nervous system cns however neuropathological electrophysiological imaging studies demonstrated peripheral nervous system pns also involved demyelination lesser extent axonal degeneration representing main pathophysiological mechanisms aim purpose study assess pns damage lumbar plexus sciatic nerve anatomical locations people relapsingremitting ms rrms healthy controls hcs vivo using magnetisation transfer ratio mtr known imaging biomarker sensitive alterations myelin content neural tissue previously explored context pns damage ms method eleven hcs 7 female mean age 336 years range 2450 15 people rrms 12 female mean age 385 years range 3056 recruited study underwent magnetic resonance imaging mri investigations together clinical assessments using expanded disability status scale edss magnetic resonance neurography mrn first used visualisation identification lumbar plexus sciatic nerve mtr imaging subsequently performed using identical scan geometry mrn enabling straightforward coregistration data obtain global regional mean mtr measurements linear regression models used identify differences mtr values hcs people rrms identify association mtr measures edss results mtr values sciatic nerve people rrms found significantly lower compared hcs significant mtr changes identified lumbar plexus people rrms median edss people rrms 20 range 03 relationship mtr measures pns edss identified anatomical locations studied cohort people rrms conclusion results study demonstrate presence pns damage people rrms support notion changes suggestive demyelination maybe occurring independently different anatomical locations within pns investigations confirm findings clarify pathophysiological basis alterations warrantedpmid34899579 pmcpmc8654928 doi103389 fneur2021763143,1.0
interleukin 17 family members health disease int immunol 2021 oct 6dxab075 doi 101093 intimm dxab075 online ahead printabstractthe interleukin17 il17 family consists six family members il17ail17f corresponding receptors identified recently family mainly involved host defense mechanisms bacteria fungi helminth infection inducing cytokines chemokines recruiting neutrophils inducing antimicrobial proteins modifying thelper cell differentiation il17a family cytokines also involved development psoriasis psoriatic arthritis ankylosing spondylitis inducing inflammatory cytokines chemokines antibodies il17a well receptor il17ra successfully used treatment diseases involvement development inflammatory bowel disease multiple sclerosis rheumatoid arthritis tumors also suggested animal disease models review will briefly review mechanisms il17 cytokines involved development diseases discuss possible treatment inflammatory diseases targeting il17 family memberspmid34611705 doi101093 intimm dxab075,0.0
primary peripheral epsteinbarr virus infection can lead cns infection neuroinflammation rabbit model implications multiple sclerosis pathogenesis front immunol 2021 nov 25 12764937 doi 103389 fimmu2021764937 ecollection 2021abstractepsteinbarr virus ebv common herpesvirus associated malignant nonmalignant conditions accumulating body evidence supports role ebv pathogenesis multiple sclerosis ms demyelinating disease cns however little known details link ebv ms one obstacle hindered research area lack suitable animal model recapitulating natural infection humans recently shown healthy rabbits susceptible ebv infection viral persistence animals mimics latent infection humans used rabbit model investigate peripheral ebv infection can lead infection cns potential consequences injected ebv intravenously one group animals phosphatebuffered saline pbs another without immunosuppression histopathological changes viral dynamics examined peripheral blood spleen brain spinal cord using range molecular histopathology techniques investigations uncovered important findings previously addressed showed primary peripheral ebv infection can lead virus traversing cns cell associated free virus plasma correlated cns infection infected cells within brain found blymphocytes notably animals injected ebv pbs developed inflammatory cellular aggregates cns incidence aggregates increased immunosuppressed animals cellular aggregates contained compact clusters macrophages surrounded reactive astrocytes dispersed b t lymphocytes myelinated nerve fibers moreover studying ebv infection span 28 days revealed peak point viral load periphery cns coincides increased occurrence cellular aggregates brain finally peripheral ebv infection triggered temporal changes expression latent viral transcripts cytokines brain present study provides first direct vivo evidence role peripheral ebv infection cns pathology highlights unique model dissect viral mechanisms contributing development mspmid34899715 pmcpmc8656284 doi103389 fimmu2021764937,1.0
lps induced pyroptosis exacerbates bmpr2 signaling deficiency potentiate slepah abstractpulmonary arterial hypertension pah common fatal complication systemic lupus erythematosus sle whether bmp receptor deficiency found genetic form pah also involved slepah patients remains identified study employed patientderived samples sleassociated pah slepah established comparable mouse models clarify role bmp signaling pathobiology slepah firstly serum levels lps autoantibodies autoabs directed bmp receptors significantly increased patients slepah compared control subjects measured elisa mass cytometry applied compare peripheral blood leukocyte phenotype patients prior treatment steroids demonstrated inflammatory cells alteration slepah furthermore bmpr2signaling pyroptotic factors examined human pulmonary arterial endothelial cells paecs response lps stimulation interleukin8 il8 eselectin sele expressions upregulated autologous bmpr2+ r899x endothelial cells sibmpr2interfered paecs sleph model established mice induced pristane hypoxia moreover combination endothelial specific bmpr2knockout sle mice exacerbated pulmonary hypertension pyroptotic factors including gasdermin d gsdmd elevated lungs sleph mice pyroptotic effects serum samples isolated slepah patients paecs analyzed bmpr2signaling upregulator bur1 showed antipyroptotic effects sleph mice paecs results implied deficiencies bmpr2signaling proinflammatory factors together contribute development pah sle,0.0
exercise neuropathic pain systematic review expert consensus front med lausanne 2021 nov 24 8756940 doi 103389 fmed2021756940 ecollection 2021abstractbackground neuropathic pain np severe disruptive symptom following many diseases normally restricts patients physical functions leads anxiety depression economical effective therapy exercise may helpful np management however guidelines reviews focused exercise therapy np associated specific diseases study aimed summarize effectiveness efficacy exercise various diseases np supported evidence describe expert recommendations np different causes inform policymakers guidelines design systematic review expert consensus methods systematic search conducted pubmed included systematic review metaanalysis randomized controlled trials rcts assessed patients np studies involved exercise intervention outcome included pain intensity least physiotherapy evidence database assessment multiple systematic reviews tool used grade quality assessment included rcts systematic reviews respectively final grades recommendation based strength evidence consensus discussion results delphi rounds delphi consensus panel including 21 experts chinese association rehabilitation medicine results eight systematic reviews 21 rcts fulfilled inclusion criteria included used create 10 evidencebased consensus statements 10 expert recommendations regarding exercise np symptoms relevant following 10 different diseases spinal cord injury stroke multiple sclerosis parkinsons disease cervical radiculopathy sciatica diabetic neuropathy chemotherapyinduced peripheral neuropathy hiv aids surgery respectively exercise recommended expert consensus involved limited muscle stretching strengthening resistance exercise aerobic exercise motor control stabilization training mindbody exercise tai chi yoga conclusions based available evidence exercise helpful alleviate np intensity therefore expert consensuses recommend proper exercise programs can considered effective alternative treatment complementary therapy patients np expert consensus provided medical staff policymakers applicable recommendations formulation exercise prescription np consensus statement will require regular updates fiveten yearspmid34901069 pmcpmc8654102 doi103389 fmed2021756940,0.0
effect obesity retinal integrity african americans caucasian americans relapsing multiple sclerosis front neurol 2021 nov 24 12743592 doi 103389 fneur2021743592 ecollection 2021abstractobjective study effect obesity retinal structures african americans aas caucasian americans cas relapsingremitting multiple sclerosis rrms methodology 136 patients rrms without history optic neuritis divided two groups based body mass index bmi 67 obese 40 aa 27 ca mean bmi sd 367 58 69 nonobese 23 aa 46 ca mean bmi sd 240 31 peripapillary retinal nerve fiber layer prnfl thickness quantified optical coherence tomography oct segmented quadrant thickness superior s inferior temporal t nasal n papillomacular bundle pmb thickness retinal nerve fiber layer rnfl ganglion cell + inner plexiform layer gcipl inner nuclear inl outer plexiform opl outer nuclear onl total macular tmv volumes obtained results obesity associated lower t thickness 5854 152 vs 619 124 p 0044 higher inl 098 007 vs 096 006 p 0034 lower rnfl 077 014 vs 082 012 p 0009 volumes obese aa significantly thinner t 5854 1519 vs 6191 1239 p 0033 n 6894 27 vs 7794 33 p 0044 tmv 815 007 vs 852 009 p 0003 rnfl 074 002 vs 082 002 p 0013 opl 076 001 vs 079 01 p 0050 onl 168 0031 vs 179 0038 p 0026 gcipl 178 004 vs 19 005 p 0038 compared obese ca among patients nonobesity onl significantly lower aa 178 004 vs 19 005 p 0001 conclusions obesity associated retinal structure abnormalities patients rrms impact might prominent aa ca large longitudinal studies needed validate findingspmid34899566 pmcpmc8651698 doi103389 fneur2021743592,0.0
univariable multivariable twosample mendelian randomization investigating effects leisure sedentary behaviors risk lung cancer front genet 2021 nov 24 12742718 doi 103389 fgene2021742718 ecollection 2021abstractleisure sedentary behaviors lsb widespread observational studies provided emerging evidence lsb play role development lung cancer lc however causal inference lsb lc remains unknown methods utilized univariable uvmr multivariable twosample mendelian randomization mvmr analysis disentangle effects lsb risk lc mr analysis conducted genetic variants genomewide association studies lsb 408 815 persons uk biobank containing 152 singlenucleotide polymorphisms snps television tv watching 37 snps computer use four snps driving lc international lung cancer consortium 11 348 cases 15 861 controls multiple sensitivity analyses performed verify causality results uvmr demonstrated genetically predisposed 15h increase lsb spent watching tv increased odds lc 90 odds ratio 190 95 confidence interval ci 144250 p 0001 similar trends observed squamous cell lung cancer 197 95ci 131294 p 00010 lung adenocarcinoma 164 95ci 112239 p 00110 causal effects remained significant adjusting education 197 95ci 144268 p 0001 body mass index 186 95ci 136254 p 0001 mvmr approach association found prolonged lsb spent computer use driving lc risk genetically predisposed prolonged lsb additionally correlated smoking 1557 95ci 12871884 p 0001 alcohol consumption 1010 95ci 10041016 p 00016 consistency results across complementary sensitivity mr methods strengthened causality conclusion robust evidence demonstrated independent causal effect lsb spent watching tv increasing risk lc work necessary investigate potential mechanismspmid34899835 pmcpmc8651878 doi103389 fgene2021742718,0.0
repeated administration 2hydroxypropylcyclodextrin hpcd attenuates chronic inflammatory response experimental stroke globally 67 million people living effects ischemic stroke importantly many stroke survivors develop chronic inflammatory response may contribute cognitive impairment common debilitating sequela stroke insufficiently studied currently untreatable 2hydroxypropylcyclodextrin hpcd fdaapproved cyclic oligosaccharide can solubilize entrap lipophilic substances goal present study determine whether repeated administration hpcd curtails chronic inflammatory response stroke reducing lipid accumulation within stroke infarcts distal middle cerebral artery occlusion mouse model stroke achieve goal subcutaneously injected young adult aged male mice vehicle hpcd three times per week treatment beginning one week stroke evaluated mice 7 weeks following stroke using immunostaining rna sequencing lipidomic behavioral analyses chronic stroke infarct periinfarct regions hpcdtreated mice characterized upregulation genes involved lipid metabolism downregulation genes involved innate adaptive immunity reactive astrogliosis chemotaxis correspondingly hpcd reduced accumulation lipid droplets t lymphocytes b lymphocytes plasma cells stroke infarcts repeated administration hpcd also preserved neun immunoreactivity striatum thalamus cfos immunoreactivity hippocampal regions additionally hpcd improved recovery protection hippocampaldependent spatial working memory reduction impulsivity results indicate systemic hpcd treatment following stroke attenuates chronic inflammation secondary neurodegeneration prevents poststroke cognitive declinesignificance statementdementia common debilitating sequela stroke currently available treatments poststroke dementia study shows lipid metabolism disrupted chronic stroke infarcts causes accumulation uncleared lipid debris correlates chronic inflammatory response knowledge substantial changes lipid homeostasis previously recognized investigated context ischemic stroke also provide proof principle solubilizing entrapping lipophilic substances using hpcd effective strategy treating chronic inflammation stroke cns injuries propose using hpcd prevention poststroke dementia improve recovery increase longterm quality life stroke sufferers,0.0
retrospective analysis postmortem findings domestic ducks geese noncommercial flocks sweden 20112020 background small poultry flock ownership become popular hobby europe north america recent years general lack information regarding bird health welfare retrospective analysis routine postmortem cases noncommercial anseriform poultry aimed providing information causes mortality mostly relation mortality events purpose birds submitted routine postmortem diagnostics national veterinary institute sva sweden 20112020 retrospectively reviewed determine main causes mortalityresultsrecords 79 necropsy submissions involving 120 birds domestic ducks n 41 muscovy ducks n 45 hybrid ducks n 2 domestic geese n 32 retrieved analysed submissions 722 represented flock disease events unexpected mortality common cause submission 709 submissions twentytwo submissions 278 referred veterinarians wide range diagnoses infectious noninfectious aetiologies infectious causes mortality included parasitic 192 bacterial 133 fungal 100 viral infections 33 bird level 120 birds infections duck virus enteritis dve highly pathogenic influenza hpai h5n8 muscovy ducks leucocytozoonosis leucocytozoon sp three species likely acquired contact wild freeliving waterfowl generalised yeast infection muscovy duck disease diagnosed muscovy ducks muscovy duck domestic duck hybrid diseases related generalised noninfectious causes 275 birds including diseases kidney disease amyloidosis cardiac dilatation reproductive diseases idiopathic inflammatory conditions nutritional managementrelated diseases diagnosed 142 birds including rickets gastrointestinal impaction obstruction congenital developmental neoplastic toxic traumatic causes mortality rareconclusionsthe information obtained study can used identify evaluate risks help owners veterinarians prevent disease provide adequate veterinary care noncommercial anseriform poultry,0.0
brazilian society rheumatology 2020 guidelines psoriatic arthritis abstractpsoriatic arthritis psa chronic systemic immune disease characterized inflammation peripheral axial joints entheses patients psoriasis pso extraarticular extracutaneous manifestations numerous comorbidities can also present recommendations replace previous version published may 2013 systematic review literature retrieved 191 articles used formulate 12 recommendations response 12 clinical questions divided 4 sections diagnosis nonpharmacological treatment conventional drug therapy biologic therapy guidelines provide evidencebased information clinical management psa patients recommendation level evidence highest available degree strength oxford degree expert agreement interrater reliability reported,0.0
qualityoflife evaluation study assessing healthrelated quality life patients receiving medicinal cannabis quest initiative protocol longitudinal observational study jmir res protoc 2021 nov 24 10 11 e32327 doi 102196 32327abstractbackground evidence supports several countries introducing legislation allow cannabisbased medicine adjunctive treatment symptomatic relief chronic pain chemotherapyinduced nausea spasticity multiple sclerosis ms epileptic seizures depression anxiety however clinical trial participants represent entire spectrum disease health status seen patients currently accessing medicinal cannabis practiceobjective study aims collect realworld data evaluate healthrelated quality life patients prescribed medicinal cannabis oil describe differences time starting therapy 3 12 months therapymethods adult patients newly prescribed medicinal cannabis oil authorized prescribers special access schemes across australia will screened eligibility invited participate sample size 2142 required 3month followup participants will complete euroqol 5dimension european organization research treatment cancer quality life questionnaire30 depression anxiety stress scale21 patients global impression change patientreported outcomes measurement information system promis short form sf version 10 sleep disturbance 8b promis sf fatigue 13a questionnaires patients chronic pain conditions will also complete promis sf version 10 pain intensity 3a promis sf version 10 pain interference 8a patients movement disorders will also complete quality life neurological disorders neuroqol sf version 10 upper extremity function fine motor activities daily living chorea indicated neuroqol sf version 20 huntingtons disease healthrelated quality lifechorea 6a questionnaires will administered baseline 2 weeks titration monthly 3 months every 2 months 1 yearresults recruitment commenced november 2020 june 2021 1095 patients screened study 69 physicians centers across 6 australian states australian capital territory new south wales queensland south australia victoria western australia patients screened 833 39 target sample size provided consent completed baseline questionnaires results expected published 2022 results study will show whether patientreported outcomes improve patients accessing prescribed medicinal cannabis baseline 3 months whether changes maintained 12month period study will also identify differences improvements patientreported outcomes among patients different chronic conditions eg chronic pain ms epilepsy parkinson disease cancer conclusions protocol contains detailed methods will used across multiple sites australia findings study potential integral treatment assessment recommendations patients chronic pain health indicators accessing medicinal cannabistrial registration australian new zealand clinical trials registry anzctrn12621000063819 https wwwanzctrorgau trial registration trialreviewaspxid380807isreviewtrueinternational registered report identifier irrid derr1102196 32327pmid34821570 doi102196 32327,0.0
pilates exercises improve balance patients multiple sclerosis systematic review metaanalysis abstractintroduction purpose balance problems common people multiple sclerosis ms pilates can also treatment strategy people ms inadequate evidence support refute efficacy pilates especially balance ms patientsthe aim study conduct systematic review metaanalysis determine effects pilates exercises balance people msmethods conducted literature search cochrane library medline ebsco physiotherapy evidence database pedro cinahl ebsco pubmed ovid science direct scopus databases using following search terms multiple sclerosis pilates core stability balance equilibrium postural control content date database inception march 2021 included searchresults initial search strategy based date range language yielded 246 relevant records eight pilates ms according evaluation found significant advantage pilates balance patients ms compared control group berg balance scale smd1017 95 ci0040 1994 p0041 activities activitiesspecific balance confidence scale smd0604 95 ci0078 1130 p0024 timed go test smd0944 95 ci0022 1867 p0045 functional reach test smd1846 95 ci0080 3772 p0060 didnnullt found difference groupsconclusions pilates exercises might optional method improving balance ms patients however need robust studies prove whether effective physiotherapy interventions,0.0
value hackathons integrated knowledge translation ikt research waterlupus background despite growing movement toward knowledgeuserdriven research process understanding generation implementation evaluation specific approaches integrated knowledge translation ikt toolbox aim engage health healthcare knowledge users limited health hackathons offer innovative approach potential generate direct indirect healthrelated outcomes benefitting participants knowledge users broader population may 2019 research team hosted waterlupus health hackathon improve economic lives individuals systemic lupus erythematosus sle canada waterlupus held multistakeholder group 50 participants included advocacy organization representatives policymakers researchers physicians individuals lived experience students hackathon generated viable solutions potential positively impact lives individuals sle understanding participants perceived hackathon ikt tool critical planning implementation future ikt researchmethodssemistructured indepth telephone interviews conducted waterlupus participants n 13 august november 2019 1 explore participant experiences hackathon 2 investigate participantidentified hackathon outcomes 3 elicit recommendations future ikt research using health hackathonsresultsparticipants provided feedback format organization waterlupus identified direct indirect outcomes knowledge users students researchers beyond innovations generated event majority n 11 never participated hackathon prior waterlupus 13 stated participate future hackathons positive outcomes identified include connecting students sle stakeholders formation professional support networks increased awareness sle well innovations generated participant recommendations future health hackathons include addition stakeholders industry technology need clear designated roles stakeholders ensure efficient use resourcesconclusionsthis work contributes limited literature regarding use health hackathons social innovation offers knowledgeuser suggestions relevant implementation future ikt events hackathons specifically,0.0
exogenous abscisic acid priming modulates water relation responses two tomato genotypes contrasting endogenous abscisic acid levels progressive soil drying elevated co2 front plant sci 2021 nov 24 12733658 doi 103389 fpls2021733658 ecollection 2021abstractplants evolved multiple strategies survive adapt confronting changing climate including elevated co2 concentration e co2 intensified drought stress explore role abscisic acid aba modulating response plant water relation characteristics progressive drought ambient co2 400 ppm e co2 800 ppm growth environments two tomato solanum lycopersicum genotypes ailsa craig ac abadeficient mutant flacca grown pots treated without exogenous aba exposed progressive soil drying plant available water pot depleted results showed exogenous aba application improved leaf water potential osmotic potential leaf turgor increased leaf aba concentrations aba leaf ac flacca genotypes exogenous aba application decreased stomatal pore aperture stomatal conductance g s though effects less pronounced e co2 grown ac g s abatreated flacca gradually increased soil water threshold g s started decline addition abatreated flacca showed partly restored stomatal drought response even accumulation aba leaf vanished implying aba leaf might directly responsible decreased g s soil drying aba leaf remained higher e co2 grown plants compared co2 high xylem sap aba concentration also noticed abatreated flacca especially e co2 suggesting e co2 might exert effect aba degradation redistribution collectively finetune aba homeostasis combined e co2 drought stress allowed plants optimize leaf gas exchange plant water relations yet detailed research regarding aba metabolism still needed fully explore role aba mediating plant physiological response future drier co2enriched climatepmid34899772 pmcpmc8651563 doi103389 fpls2021733658,0.0
transcriptome sequencing identified cerna network associated recurrent spontaneous abortion background recurrent spontaneous abortion rsa one common complication pregnancy bringing heavy burden patients families study aimed explore lncrnamirnamrna network associated recurrent spontaneous abortionmethodsby transcriptome sequencing detected differences lncrna mirna mrna expression villus tissue samples collected 3 patients rsa 3 normal abortion patients differentially expressed lncrnas mirnas genes dels dems degs respectively identified geno ontology go kyoto encyclopedia genes genomes kegg analyses used determine functions dels degs analysed fishers test also observed regulatory relationships mirnamrna lncrnamirna cytoscape 361resultsthe results showed 1008 dels 523 upregulated 485 downregulated 475 degs 201 upregulated 274 downregulated 37 dems 15 upregulated 22 downregulated identified also constructed novel lncrnarelated cerna network containing 31 lncrnas 1 mirna hsamir2105p 3 genes ntng2 gria1 aqp1 conclusionslncrnarelated cerna network containing 31 lncrnas 1 mirna hsamir2105p 3 mrnas ntng2 gria1 aqp1 constructed results may provide basic theory elucidating mechanism underlying rsa,0.0
incidence malignancy multiple sclerosis cohort study danish multiple sclerosis registry mult scler j exp transl clin 2021 nov 23 7 4 20552173211053939 doi 101177 20552173211053939 ecollection 2021 octabstractbackground association multiple sclerosis malignancy controversial current appraisal neededobjective determine incidence malignancy patients multiple sclerosis compared general population relation diseasemodifying therapymethods patients multiple sclerosis 1995 2015 matched birth year sex individuals without multiple sclerosis general population patients multiple sclerosis initiating diseasemodifying therapy evaluated using landmark period analysis malignancy risk assessed incidence rates incidence rate ratios standardised incidence ratiosresults standardised incidence ratio malignancy excluding nonmelanoma skin cancer patients multiple sclerosis n 10 557 096 95 ci 088 106 increased incidence specific malignancy types compared general population cohort n 103 761 48month landmark period ageadjusted incidence per 100 000 personyears malignancy excluding nonmelanoma skin cancer 4367 95 ci 3610 5124 patients newly treated immunomodulatoronly 6751 95 ci 1304 12199 patients newly treated immunosuppressantonlyconclusions increased incidence malignancy overall type patients multiple sclerosis compared neither general population relation diseasemodifying therapypmid34840804 pmcpmc8613897 doi101177 20552173211053939,0.0
correlation symbol digit modalities test quality life depression japanese patients multiple sclerosis abstractbackground study aimed evaluate association cognitive impairment healthrelated quality life hrqol fatigue depression japanese patients multiple sclerosis ms methods brief international cognitive assessment ms bicams performed 184 japanese patients ms functional assessment ms fams fatigue severity scale fss beck depression inventorysecond edition bdiii used evaluate hrqol fatigue depression respectivelyresults multiple linear regression analysis demonstrated positive correlations symbol digit modalities test sdmt scores fams subscales mobility symptoms emotional wellbeing additional concerns total fams score even controlling expanded disability status scale score age examination duration education sdmt score bicams battery negative correlations bdiii score revealed multiple linear regression analysis none three tests bicams correlation fss scoreconclusion sdmt significant relationship hrqol depression japanese patients ms,0.0
proinflammatory diet associated increased likelihood first clinical diagnosis central nervous system demyelination women abstractbackground number studies examined associations dietary factors risk multiple sclerosis ms little known intakes inflammationmodulating foods nutrients risk msobjectives test associations dietary inflammatory index dii risk first clinical diagnosis central nervous system cns demyelination fcd 267 cases 507 controls using data ausimmune studymethods 20032006 ausimmune study multicentre matched casecontrol study examining environmental risk factors fcd common precursor ms dii wellrecognised tool categorises individualsnull diets continuum maximally antiinflammatory maximally proinflammatory dii score calculated dietary intake data collected using food frequency questionnaire conditional logistic regression models used estimate association dii fcd separately men womenresults women higher dii score associated increased likelihood fcd 17 increase likelihood fcd per oneunit increase dii score adjusted odds ratio 117 95 confidence interval 104133 association dii fcd men adjusted odds ratio 088 95 confidence interval 073107 conclusions findings suggest proinflammatory diet associated increased likelihood fcd women,1.0
myelin quantification white matter pathology progressive multiple sclerosis postmortem brain samples new approach quantifying remyelination int j mol sci 2021 nov 23 22 23 12634 doi 103390 ijms222312634abstractmultiple sclerosis ms demyelinating neurodegenerative disease central nervous system cns repair remyelination can extensive quantification remyelination remains challenging date method standardized digital quantification remyelination ms lesions exists methodological study aims present validate novel standardized method myelin quantification progressive ms brains study myelin content precisely fiftyfive ms lesions 32 tissue blocks 14 progressive ms cases five tissue blocks 5 nonneurological controls sampled ms lesions selected macroscopic investigation wm standard histopathological methods tissue sections stained myelin luxol fast blue lfb histological assessment de remyelination performed light microscopy myelin quantity estimated novel myelin quantification method mqm imagej three independent raters applied mqm interrater reliability calculated extended method diffusely appearing white matter dawm encephalitis test potential wider applicability method interrater agreement excellent icc 096 high reliability lower upper limit agreement 593 1843 variation myelin quantity study builds established concepts histopathological semiquantitative assessment myelin adds novel reliable accurate quantitative measurement tool assessment myelination human postmortem samplespmid34884445 doi103390 ijms222312634,1.0
neuroprotection ketogenic diet evidence controversies front nutr 2021 nov 23 8782657 doi 103389 fnut2021782657 ecollection 2021abstractthe ketogenic diet kd highfat lowcarbohydrate diet used decades nonpharmacologic approach treat metabolic disorders refractory pediatric epilepsy recent years enthusiasm kd increased scientific community due evidence diet reduces pathology improves various outcome measures animal models neurodegenerative disorders including multiple sclerosis stroke glaucoma spinal cord injury retinal degenerations parkinsons disease alzheimers disease clinical trials also suggest kd improved quality life patients multiple sclerosis alzheimers disease furthermore major ketone bodies bhb aca potential neuroprotective properties now known direct effects specific inflammatory proteins transcription factors reactive oxygen species mitochondria epigenetic modifications composition gut microbiome neuroprotective benefits kd likely due combination cellular processes potential mechanisms yet confirmed experimentally review provides comprehensive summary current evidence effectiveness kd humans preclinical models various neurological disorders describes molecular mechanisms may contribute beneficial effects highlights key controversies current gaps knowledgepmid34888340 pmcpmc8650112 doi103389 fnut2021782657,1.0
mri big data artificial intelligence rewards versus risks neurology 2021 oct 4101212 wnl0000000000012883 doi 101212 wnl0000000000012883 online ahead printno abstractpmid34607921 doi101212 wnl0000000000012883,0.0
three decades cdk5 abstractcdk5 prolinedirected serine threonine protein kinase governs variety cellular processes neurons dysregulation compromises normal brain function mechanisms underlying modulation cdk5 modes action effects nervous system great focus field nearly three decades review provide overview discovery regulation cdk5 highlighting recent findings revealing role neuronal synaptic functions circadian clocks dna damage cell cycle reentry mitochondrial dysfunction well nonneuronal functions physiological pathological conditions moreover discuss evidence underscoring aberrant cdk5 activity common theme observed many neurodegenerative diseases,0.0
recognizing visual complaints people multiple sclerosis prevalence nature associations key characteristics ms abstractbackground visual disturbances common multiple sclerosis ms visual complaints may underestimated complaints decrease quality life may discussed clinic visits people ms pwms may referred appropriate care therefore investigated prevalence nature associations visual complaints pwmsmethodswe performed cohort study comparison group pwms n493 healthy controls n661 filled screening visual complaints questionnaire svcq primary outcomes percentage pwms controls reported 19 complaints total scores svcq also compared scores svcq different groups pwmsresultsin general complaints reported often pwms controls pwms especially reported experiencing complaints often alwaysnull controls reported complaints primarily sometimesnull pwms without history optic neuritis showed similar complaints pwms longer disease duration spms reported complaints edss score disease duration showed limited association discomfort visual complaintsconclusionthe prevalence visual complaints among pwms high pwms may experience wide array different visual complaints anywhere along disease course regardless history optic neuritis using svcq may help detect pwmsnull visual complaints may facilitate referrals appropriate care,0.0
ophthalmic rosaidorfman disease multicentre comprehensive study background provide basic demographic information clinicopathologic features ophthalmic rosaidorfman disease rdd literature reviewmethodsa multicentre retrospective case series reviewing patients histopathologically confirmed ophthalmic rdd three tertiary eye care centres january 1993 december 2018resultseleven eyes eight patients histopathologically confirmed ophthalmic rdd included equal numbers males females median age 4025 years range 266724 two patients familial rdd orbit commonly involved site 909 eyes one patient one eye presented scleral nodule anterior uveitis cystoid macular oedema visual acuity ranged 20 25 light perception six patients extranodal ophthalmic disease remaining two associated submandibular lymphadenopathy nodal rdd conclusionsophthalmic rdd can manifestation systemic disease orbit commonly involved site exhibiting bone destruction intracranial sinus involvement variable degree visual loss ophthalmic familial rdd represent severe form malignant course steroid monotherapy may inadequate control orbital rdd thus combined treatment usually necessary comprehensive approach assessment management recommended,0.0
cardiorespiratory fitness moderatetovigorous physical activity older adults multiple sclerosis mult scler j exp transl clin 2021 nov 23 7 4 20552173211057514 doi 101177 20552173211057514 ecollection 2021 octabstractbackground cardiorespiratory fitness vo2peak may modifiable indicator health status wellbeing older adults multiple sclerosispurpose examined differences vo2peak moderatetovigorous physical activity older adults multiple sclerosis healthy controls whether moderatetovigorous physical activity accounted group differences vo2peakmethods older adults multiple sclerosis n 31 healthy controls n 29 completed cardiopulmonary exercise test wore accelerometer measuring moderatetovigorous physical activity data analyzed using baron kenny approach examining moderatetovigorous physical activity mediator group differences vo2peakresults multiple sclerosis group significantly lower vo2peak moderatetovigorous physical activity healthy controls vo2peak large correlation moderatetovigorous physical activity r 59 group initially explained 8 variance vo2peak 029 inclusion moderatetovigorous physical activity accounted additional 27 variance vo2peak moderatetovigorous physical activity 057 statistically significant correlate vo2peak effect group attenuated nonsignificant addition moderatetovigorous physical activity step 2 group step 1 029 group step 2 005 conclusions results provide initial support targeting moderatetovigorous physical activity approach improving vo2peak older adults multiple sclerosispmid34868628 pmcpmc8640293 doi101177 20552173211057514,0.0
opportunities understanding ms mechanisms progression mri using largescale data sharing artificial intelligence neurology 2021 oct 4101212 wnl0000000000012884 doi 101212 wnl0000000000012884 online ahead printabstractmultiple sclerosis ms patients heterogeneous clinical presentations symptoms progression time making ms difficult assess comprehend vivo combination largescale datasharing artificial intelligence creates new opportunities monitoring understanding ms using magnetic resonance imaging mri first development validated msspecific image analysis methods can boosted verified reference test benchmark imaging data using detailed expert annotations artificial intelligence algorithms can trained msspecific data second understanding disease processes greatly advanced shared data large ms cohorts clinical demographic treatment information relevant patterns data may imperceptible human observer detected artificial intelligence techniques applies image analysis lesions atrophy functional network changes large multidomain datasets imaging cognition clinical disability genetics etc reviewing datasharing artificial intelligence paper highlights three areas offer strong opportunities making advances next years crowdsourcing personal data protection organized analysis challenges difficulties well specific recommendations overcome discussed order best leverage data sharing artificial intelligence improve image analysis imaging understanding mspmid34607924 doi101212 wnl0000000000012884,0.0
neural processes psychological stress relaxation predict future evolution quality life multiple sclerosis front neurol 2021 nov 23 12753107 doi 103389 fneur2021753107 ecollection 2021abstracthealthrelated quality life hrqol essential complementary parameter assessment disease burden treatment outcome multiple sclerosis ms can affected neuropsychiatric symptoms turn sensitive psychological stress however now impact neurobiological stress relaxation hrqol ms investigated thus evaluated whether activity neural networks triggered mild psychological stress elicited fmri task comprising mental arithmetic feedback stress termination ie relaxation baseline t0 predicts hrqol variations occurring t0 followup visit t1 28 patients using robust regression permutation testing median delay t0 t1 902 range 3631 169 days assessed hrqol based hamburg quality life questionnaire ms haquams accounted impact established hrqol predictors cognitive performance participants relaxationtriggered activity widespread neural network predicted future variations overall hrqol t 368 p familywise error fwe corrected 0008 complementary analyses showed relaxationtriggered activity network baseline associated variations haquams mood subscale fwe 01 level t 337 p fwe 0087 finally stressinduced activity prefrontolimbic network predicted future variations haquams lower limb mobility subscale t 362 p fwe 0020 functional neural network measures psychological stress relaxation contain prognostic information future hrqol evolution ms independent clinical predictorspmid34887828 pmcpmc8650716 doi103389 fneur2021753107,0.0
complementary medicine germany multicentre crosssectional survey usage needs ofpatients hospitalized university medical centers background results recent surveys indicate 50 german population experience complementary alternative medicine cam uses cam regularly study investigated cam usage camrelated needs hospitalized patients university medical centres state badenwrttemberg germanymethodsa multicentre paperbased pseudonymous survey carried members academic centre complementary integrative medicine patients ages regardless sex diagnosis treatment hospitalized department cardiology gastroenterology oncology gynaecology surgery university medical centres freiburg heidelberg tbingen ulm eligible inclusionresultsof 1275 eligible patients 67 n 854 consented participate survey fortyeight percent study participants stated currently using cam frequently used therapies exercise 63 herbal medicine 54 dietary supplements 53 16 patients discussed cam usage attending physician half patients 48 interested cam consultations 80 patients desired reliable cam information stated physicians better informed camconclusionsthe frequency cam usage need cam counselling among hospitalized patients university medical centres badenwrttemberg high better meet patients needs cam research physician education intensifiedtrial registrationgerman clinical trial register drks00015445,0.0
association cytokines psychomotor speed spectrum psychotic disorders longitudinal study brain behav immun health 2021 nov 23 18100392 doi 101016 jbbih2021100392 ecollection 2021 decabstractbackground schizophrenia impaired psychomotor speed common symptom predicting worse functional outcome inflammation causes changes white matter integrity may lead reduced psychomotor speed therefore wanted investigate peripheral inflammation assessed cytokines affected performance psychomotor speed patients spectrum psychotic disordersmethods current study prospective cohort study including participants pragmatic randomised controlled trial comparing three atypical antipsychotics patients spectrum psychotic disorders purposes substudy analysed drug treatment groups collectively psychomotor speed assessed baseline weeks 6 12 26 52 followup using neuropsychological tests trail making test tmt b symbol coding serum concentration following cytokines measured interleukin il il2 il4 il6 il10 il12 p70 il17a interferon ifn tumor necrosis factor tnf blood samples collected baseline 1 3 6 12 26 39 52 weeks analysed effect cytokines levels psychomotor speed time linear mixed effects modelsresults linear mixed effects models controlling possible confounders ifn significant negative effect tmta symbol coding performance none tests psychomotor speed significantly associated cytokines overall psychomotor speed performance increased significantly across study period cytokine levels remained stableconclusion study indicates negative association ifn psychomotor speed might importance understanding mechanisms behind psychomotor deviations psychotic disorderspmid34877553 pmcpmc8633579 doi101016 jbbih2021100392,0.0
hypogammaglobulinemia infections patients multiple sclerosis treated rituximab neurol neuroimmunol neuroinflamm 2021 nov 23 9 1 e1115 doi 101212 nxi0000000000001115 print 2022 janabstractbackground objectives determine frequency hypogammaglobulinemia infections patients multiple sclerosis pwms receiving rituximab rtx methods prospective observational study included consecutive pwms receiving rtx university hospital marseille france 2015 2020 patient visits occurred least every 6 monthsresults included 188 patients 151 relapsingremitting ms mean age 434 years sd 129 median disease duration 10 years range 036 median expanded disability status scale 5 range 08 median followup 35 years range 158 median number rtx infusions 5 range 19 overall 317 symptomatic infections 13 severe infections occurred 133 188 707 11 188 59 patients respectively 4 years 244 patients 95 ci 180331 free infection 920 95 ci 871971 experienced severe infection rtx onset immunoglobulin g igg level abnormal 32 188 17 patients rtx igg level 7 6 4 2 g l 83 44 44 234 8 42 1 053 patients respectively risk infection associated reduced igg levels multivariate cox proportional hazards hazard ratio hr 086 95 ci 075098 p 003 risk reduced igg level 6 g l increased age hr 136 95 ci 105175 p 001 discussion pwms receiving rtx reduced igg level frequent interacted risk infectionpmid34815322 doi101212 nxi0000000000001115,0.0
identifying diseasecritical cell types cellular processes across human body integration singlecell profiles human genetics biorxiv 2021 nov 2320210319436212 doi 101101 20210319436212 preprintabstractgenomewide association studies gwas provide powerful means identify loci genes contributing disease many cases related cell types states genes confer disease risk remain unknown deciphering relationships important identifying pathogenic processes developing therapeutics introduce sclinker framework integrating singlecell rnaseq scrnaseq epigenomic maps gwas summary statistics infer underlying cell types processes genetic variants influence disease analyzed 16 million scrnaseq profiles 209 individuals spanning 11 tissue types 6 disease conditions constructed gene programs capturing cell types disease progression cellular processes within across cell types evaluated gene programs disease enrichment transforming snp annotations tissuespecific epigenomic maps computing enrichment scores across 60 diseases complex traits average n 297k cell type disease progression cellular process programs captured distinct heritability signals even within cell type show multiple complex diseases affect brain alzheimers disease multiple sclerosis colon ulcerative colitis lung asthma idiopathic pulmonary fibrosis severe covid19 inferred disease enrichments recapitulated known biology highlighted novel celldisease relationships including gabaergic neurons major depressive disorder mdd disease progression m cell program ulcerative colitis diseasespecific complement cascade process multiple sclerosis autoimmune disease healthy disease progression immune cell type programs associated whereas epithelial cells disease progression programs prominent perhaps suggesting role disease progression initiation framework provides powerful approach identifying cell types cellular processes genetic variants influence diseasepmid34845454 pmcpmc8629197 doi101101 20210319436212,0.0
tlr4 associated signaling disrupters new means overcome hervw envelopemediated myelination deficits front cell neurosci 2021 nov 23 15777542 doi 103389 fncel2021777542 ecollection 2021abstractmyelin repair adult central nervous system cns driven successful differentiation resident oligodendroglial precursor cells opcs thus constitutes neurodegenerative process capable compensate functional deficits upon loss oligodendrocytes myelin sheaths observed multiple sclerosis ms human endogenous retrovirus type w hervw represents msspecific pathogenic entity envelope env protein previously identified negative regulator opc maturationhence relevance context diminished myelin repair focused activity env protein investigated can neutralized improved remyelination envmediated activation toll like receptor 4 tlr4 increases inducible nitric oxide synthase inos expression prompts nitrosative stress results myelinassociated deficits decreased levels oligodendroglial maturation marker expression morphological alterations intervention tlr4 surface expression represents potential means rescue envdependent deficits end rescue capacity specific substances either modulating vatpase activity myeloid differentiation 2 md2 mediated tlr4 glycosylation status compound 20 c20 l48h437 folimycin analyzed processes demonstrated relevant tlr4 surface expression found pharmacological treatment can rescue maturation arrest oligodendroglial cells myelination capacity can prevent inos induction presence env protein addition downregulation tlr4 surface expression observed furthermore mitochondrial integrity crucial oligodendroglial cell differentiation affected presence env ameliorated upon pharmacological treatment study therefore provides novel insights possible means overcome myelination deficits associated hervw envmediated myelin deficitspmid34887730 pmcpmc8650005 doi103389 fncel2021777542,1.0
association history nontyphoidal salmonella risk systemic lupus erythematosus populationbased casecontrol study front immunol 2021 nov 23 12725996 doi 103389 fimmu2021725996 ecollection 2021abstractobjective investigated correlation nontyphoidal salmonella nts infection systemic lupus erythematosus sle riskmethods casecontrol study comprised 6 517 patients newly diagnosed sle 2006 2013 patients without sle randomly selected control group matched casecontrol ratio 120 age sex index year study individuals traced index date back nts exposure relevant covariates beginning year 2000 conditional logistic regression analysis used analyze risk sle adjusted odds ratios aors 95 confidence intervals cis nts control groupsresults mean age 378 years case control groups females accounted 855 aor nts infection significantly increased sle relative controls aor 920 95 ci 4511878 120 sexage matching analysis aor 747 95 ci2082682 propensity score matching analysis subgroup analysis indicated sle risk high among dwelled rural areas rheumatoid arthritis multiple sclerosis sjogrens syndrome developed intensive severe nts infection admissionconclusions exposure nts infection associated development subsequent sle taiwanese individuals severe nts infection autoimmune diseases rheumatoid arthritis multiple sclerosis sjogrens syndrome also contributed risk developing slepmid34887848 pmcpmc8650632 doi103389 fimmu2021725996,0.0
derisking cd20therapies longterm use abstractanticd20 quickly become mainstay treatment multiple sclerosis ms neuroinflammatory conditions however used maintenance therapy balance risks benefits changes review suggested six steps derisk anticd20 firstly secondly adequate infectious screening followed vaccinations starting anticd20 paramount third family planning needs discussed upfront every woman childbearing age fourth infusion reactions adequately managed avoid treatment interruption repeated infusions becomes important detect prevent anticd20related adverse events fifth recommended measuring immunoglobulin levels reviewing vaccinations annually well counselling adequate fever management female patients emphasised importance engage local breast cancer screening programs sixth fundamentally derisk anticd20 therapies need evidencebased approaches reduce dosing intervals guide retreatment,0.0
molluscum contagiosum setting fingolimod experience one institution abstractfingolimod treatment associated opportunistic infections notably pml cryptococcal meningitis rare reports infections like molluscum contagiosum typically associated impaired cellular immunity seen aids upon review multiple sclerosis patient database identified eight patients undergoing fingolimod treatment developed molluscum contagiosum infections suspect association class effect may also observed s1p receptor modulators molluscum contagiosum infection lifethreatening can extremely distressing patients resolution may require discontinuation fingolimod,0.0
serial mediation model gratitude life satisfaction people multiple sclerosis intermediary role perceived stress mental health symptoms abstractbackground although prior research explored role gratitude individuals disabilities relatively limited research examining positive influence gratitude decreasing psychological distress promoting mental health ultimately improving wellbeing multiple sclerosis ms population study aimed examine cumulative mediating effect perceived stress mental health gratitude life satisfaction among people msmethods study crosssectional participants 373 individuals ms descriptive statistics correlation analyses serial mediation analysis performed studyresults gratitude negatively associated perceived stress mental health symptoms positively associated life satisfaction perceived stress positively associated mental health symptoms negatively associated life satisfaction mental health symptoms negatively associated life satisfaction findings demonstrated relationship gratitude life satisfaction partially mediated perceived stress mental health symptoms individuals msconclusions findings provided implications integrating gratitude interventions working people ms increasing gratitude levels people ms may turn lead reduced perceived stress mental health symptoms turn may enhance life satisfaction,0.0
measuring duchenne muscular dystrophy impact development proxyreported measure derived promis item banks background personreported outcomes measurement development rare diseases lagged behind common diseases studies caregivers patients rare diseases one relies proxy report characterize disability important measure childs disability accurately comprehensively affects caregiver burden aimed create conditionspecific caregiver proxyreport measure duchenne muscular dystrophy dmd order understand impact dmd caregiver drawing relevant item banks patientreported outcome measurement information system promis sought confirm reliability validity target sample dmd caregiversmethodsthis webbased study recruited dmd caregivers via rare patient voice patientadvocacy groups word mouth recruitment stratified age caregivers child dmd broadly represents stages dmd progression 27 812 1317 18 telephone interviews dmd parentcaregivers pretested possible measures content validity webbased study utilized algorithm categorize respondents ambulatory status tailored administration promis parentproxy items well new items developed based caregiver interviews item response theory analyses implementedresultsthe study sample included 521 dmd caregivers representing equally four age strata proxyreport measure included following domains fatigue impact strength impact cognitive function upper extremity function positive affect negative affect sleepdevice symptoms mobility first five domains strong psychometric characteristics unidimensionality acceptable model fit strong standardized factor loadings high marginal reliability negative affect covering anger anxiety depressive symptoms psychological stress fit bifactor model good model fit high marginal reliability strong factor loadings sleepdevice symptoms domain unidimensional mobility domain simple structure due residual correlations among items opposite end mobilitydisability continuum two domain scores retained clinimetric indices ie uncalibrated scales achieve overall goal contentvalid dmdspecific measure across stages disease severityconclusionsthe present study derived dmdspecific proxyreport measure promis item banks supplemental items potentially utilized caregiver research across stages care recipients dmd future research will focus assessing responsiveness validity measure time comparison dmd patient selfreport,0.0
vaccines measles mumps rubella varicella children cochrane database syst rev 2021 nov 22 11cd004407 doi 101002 14651858cd004407pub5abstractbackground measles mumps rubella varicella chickenpox serious diseases can lead serious complications disability death however public debate safety trivalent mmr vaccine resultant drop vaccination coverage several countries persists despite almost universal use accepted effectiveness update review published 2005 updated 2012objectives assess effectiveness safety long shortterm adverse effects associated trivalent vaccine containing measles rubella mumps strains mmr concurrent administration mmr vaccine varicella vaccine mmr+v tetravalent vaccine containing measles rubella mumps varicella strains mmrv given children aged 15 yearssearch methods searched cochrane central register controlled trials central cochrane library 2019 issue 5 includes cochrane acute respiratory infections groups specialised register medline 1966 2 may 2019 embase 1974 2 may 2019 international clinical trials registry platform 2 may 2019 clinicaltrialsgov 2 may 2019 selection criteria included randomised controlled trials rcts controlled clinical trials ccts prospective retrospective cohort studies pcs rcs casecontrol studies ccs interrupted timeseries studies case crossover cco studies caseonly ecological method coem studies selfcontrolled case series sccs studies persontime cohort ptc studies casecoverage design screening methods ccd sm studies assessing combined mmr mmrv mmr+v vaccine given dose preparation time schedule compared intervention placebo healthy children 15 years agedata collection analysis two review authors independently extracted data assessed methodological quality included studies grouped studies quantitative analysis according study design vaccine type mmr mmrv mmr+v virus strain study settings outcomes interest cases measles mumps rubella varicella harms certainty evidence rated using grademain results included 138 studies 23 480 668 participants fiftyone studies 10 248 159 children assessed vaccine effectiveness 87 studies 13 232 509 children assessed association vaccines variety harms included 74 new studies 2019 version review effectiveness vaccine effectiveness preventing measles 95 one dose relative risk rr 005 95 ci 002 013 7 cohort studies 12 039 children moderate certainty evidence 96 two doses rr 004 95 ci 001 028 5 cohort studies 21 604 children moderate certainty evidence effectiveness preventing cases among household contacts preventing transmission others children contact one dose 81 rr 019 95 ci 004 089 3 cohort studies 151 children low certainty evidence two doses 85 rr 015 95 ci 003 075 3 cohort studies 378 children low certainty evidence three doses 96 rr 004 95 ci 001 023 2 cohort studies 151 children low certainty evidence effectiveness least one dose preventing measles exposure postexposure prophylaxis 74 rr 026 95 ci 014 050 2 cohort studies 283 children low certainty evidence effectiveness jeryl lynn containing mmr vaccine preventing mumps 72 one dose rr 024 95 ci 008 076 6 cohort studies 9915 children moderate certainty evidence 86 two doses rr 012 95 ci 004 035 5 cohort studies 7792 children moderate certainty evidence effectiveness preventing cases among household contacts 74 rr 026 95 ci 013 049 3 cohort studies 1036 children moderate certainty evidence vaccine effectiveness rubella using vaccine brd2 strain used china 89 rr 011 95 ci 003 042 1 cohort study 1621 children moderate certainty evidence vaccine effectiveness varicella severity two doses children aged 11 22 months 95 10 years followup rate ratio rr 005 95 ci 003 008 1 rct 2279 children high certainty evidence safety evidence supporting association aseptic meningitis mmr vaccines containing urabe leningradzagreb mumps strains evidence supporting association mmr vaccines containing jeryl lynn mumps strains rr 130 95 ci 066 256 low certainty evidence analyses provide evidence supporting association mmr mmr+v mmrv vaccines jeryl lynn strain febrile seizures febrile seizures normally occur 2 4 healthy children least age 5 attributable risk febrile seizures vaccineinduced estimated 1 per 1700 1 per 1150 administered doses analyses provide evidence supporting association mmr vaccination idiopathic thrombocytopaenic purpura itp however risk itp vaccination smaller natural infection viruses natural infection itp occur 5 cases per 100 000 1 case per 20 000 per year attributable risk estimated 1 case itp per 40 000 administered mmr doses evidence association mmr immunisation encephalitis encephalopathy rate ratio 090 95 ci 050 161 2 observational studies 1 071 088 children low certainty evidence autistic spectrum disorders rate ratio 093 95 ci 085 101 2 observational studies 1 194 764 children moderate certainty insufficient evidence determine association mmr immunisation inflammatory bowel disease odds ratio 142 95 ci 093 216 3 observational studies 409 cases 1416 controls moderate certainty evidence additionally evidence supporting association mmr immunisation cognitive delay type 1 diabetes asthma dermatitis eczema hay fever leukaemia multiple sclerosis gait disturbance bacterial viral infections authors conclusions existing evidence safety effectiveness mmr mmrv vaccines support use mass immunisation campaigns aimed global eradication assess epidemiological socioeconomic situations countries well capacity achieve high vaccination coverage evidence needed assess whether protective effect mmr mmrv wane time since immunisationpmid34806766 doi101002 14651858cd004407pub5,0.0
spatial navigation performance people multiple sclerosis largescale online study abstractobjectivespatial navigation crucial function daily life activities therefore strongly linked quality life autonomy mobility navigation shown frequently impaired forms acquired brain injury impact ms navigation ability yet studied better understanding potential navigation problems population improve patient care therefore aim current study measure objective subjective navigation performance people msmethodsperformance large sample people ms n359 compared group matched controls additionally impact ambulation selfreported cognitive performance studied within ms sample participants filled wayfinding questionnaire patientreported expanded disability status scale multiple sclerosis neuropsychological screening questionnaire selfreport measures objective navigation performance measured online navigation test using virtual environmentresultsresults indicate lower subjective well objective performance people ms compared healthy controls substantial contribution selfreported cognitive performance navigation abilityconclusionsthese findings indicate spatial navigation can significant problem people ms especially people ms cognitive impairments,0.0
sarscov2 serology among people multiple sclerosis diseasemodifying therapies bbibpcorv sinopharm inactivated virus vaccination story different vaccine abstractbackgroundvarious studies indicated blunted humoral responses covid19 mrna viral vector vaccines among people multiple sclerosis pwms sphingosine 1phosphate receptor s1pr modulators anticd20 therapies acd20 however study found assessing sarscov2 serology inactivated virus vaccinationobjectiveto provide evidence regarding humoral response covid19 inactivated virus vaccination among pwms diseasemodifying therapies dmts methodsa cohort study carried isfahan iran enrolling dmtexposed pwms unexposed ux healthy participants postvaccination antisarscov2 spike igg serology testing carried among participants compared participants based dmt exposure using proper statistical tests multivariable logistic regression model used control confounding association second vaccine dosetophlebotomy vac2phleb humoral response investigated dmtexposed cohort using linear regression among acd20 cohort association last acd20 infusiontofirst vaccine dose period serostatus investigated using unpaired ttestresultsafter enrolling 358 participants 144 pwms 214 healthy blunted humoral responses observed fingolimod log10 mean diff se 072 018 p0001 acd20 log10 mean diff se 075 015 p 0001 cohorts compared ux cohort multivariable analysis confirmed results study achieve enough statistical power detect significant association vac2phleb period humoral responses last acd20 infusion first vaccination dose period longer seroconverted pwms acd20 mean diff se 843 weeks 257 p0005 conclusionthe results study mirrored results previous studies among mrna viral vectorvaccinated pwms dmts therefore can concluded mode action contributes less timing efficiency vaccination strategies among pwms dmts especially ones s1pr modulators acd20 meanwhile mentioned pwms advised receive early boosters remain vigilant data becomes available efficient vaccination strategies crafted,0.0
evidence extensive cellular immune response sarscov2 vaccination ocrelizumabtreated patients multiple sclerosis background patients multiple sclerosis receiving ocrelizumabtreatment desperate need protection sarscov2 infectionmethodsin study euroimmun semiquantitative antisarscov2 igg detection humoral response elispot assays detection sarscov2specific tcellresponse used 10 ocrelizumabtreated patients multiple sclerosis twice vaccinated comirnaty mrna vaccine data compared control group 20 age sexmatched healthy volunteers previously received full sarscov2 mrna vaccination comirnaty spikevaxresultswhile subjects control group high humoral response vaccination bcelldepleted individuals significantly reduced antibody response vaccination sarscov2 observed sarscov2 specific tcellresponse however differ significantly cohortsconclusionstcellmediated response comirnaty vaccination observable despite attenuated humoral response bcelldepleted patients might enable partial protection covid19trial registration retrospectively registered,0.0
immunosuppressors immunomodulators neurology part guide management patients underimmunotherapy abstract patients autoimmune diseases risks benefits immunosuppressive immunomodulatory treatment matter continual concern knowledge followup routine drug crucial order attain better outcomes avoid new disease activity occurrence adverse effects achieve control autoimmune diseases immunosuppressive immunomodulatory drugs act different pathways immune response knowledge mechanisms action drugs recommended doses adverse reactions risks infection malignancy essential safe treatment drug specific safety profile management adapted different circumstances treatment primary prophylaxis opportunistic infections vaccination indispensable steps treatment plan given prevent potential severe infectious complications general neurologists frequently prescribe immunosuppressive immunomodulatory drugs awareness characteristics drug crucial treatment success implementation routine use drugs avoids treatmentrelated complications enables superior disease control,0.0
german multiple sclerosis pregnancy registry rationale objective design first results ther adv neurol disord 2021 nov 22 1417562864211054956 doi 101177 17562864211054956 ecollection 2021abstractobjectives multiple sclerosis ms neuromyelitis optica spectrum disorders nmosd predominantly affect women reproductive age last decades many diseasemodifying therapies dmts approved therefore important provide epidemiological structures collection safety information exposed pregnancies data disease activity withdrawal dmts high demand especially severe relapses described ceasing highly effective dmts although breastfeeding recommended still unclear early reintroduction especially highly effective dmts beneficial effect postpartum relapse risk combination however safety data lackingmethods german ms pregnancy registry dmskw nationwide observational cohort study pregnant women ms nmosd founded 2006 study procedure undergone important adaptation recent years described updated methodology including data source acquisition well variables collected within dmskwresults december 2020 dmskw database comprises 2579 pregnancies 2568 ms 11 nmosd women enrolled median gestational week 11 range 002421 median postpartum follow 12 years range 092 76 pregnancies exposed dmt mostly first trimester spontaneous abortion preterm birth occurred 7 10 respectively 19 women suffered least one relapse pregnancy minimum 6 third trimester pregnancyconclusion dmskw valuable structure providing safety data drug exposure pregnancy lactation combination information disease activity 6 years postpartum article will reference describing methods future publications dmskwpmid34840606 pmcpmc8613898 doi101177 17562864211054956,0.0
crotalphine attenuates pain neuroinflammation induced experimental autoimmune encephalomyelitis mice toxins basel 2021 nov 22 13 11 827 doi 103390 toxins13110827abstractmultiple sclerosis ms demyelinating disease inflammatory autoimmune origin induces sensory progressive motor impairments including pain cells immune system actively participate pathogenesis progression ms inducing neuroinflammation tissue damage demyelination crotalphine cro structural analogue peptide firstly identified crotalus durissus terrificus snake venom induces analgesia endogenous opioid release type 2 cannabinoid receptor cb2 activation since cb2 activation downregulates neuroinflammation ameliorates symptoms mice models ms presently investigated whether cro beneficial effect experimental autoimmune encephalomyelitis eae cro administered 5th day immunization single dose five doses starting peak disease cro partially reverted eaeinduced mechanical hyperalgesia decreased severity clinical signs addition cro decreases inflammatory infiltrate glial cells activation followed tnf il17 downregulation spinal cord peripherally cro recovers eaeinduced impairment myelin thickness sciatic nerve therefore cro interferes central peripheral neuroinflammation opening perspectives ms controlpmid34822611 doi103390 toxins13110827,1.0
feasibility safety immersive virtual realitybased vestibular rehabilitation programme people multiple sclerosis experiencing vestibular impairment protocol pilot randomised controlled trial bmj open 2021 nov 22 11 11 e051478 doi 101136 bmjopen2021051478abstractintroduction vestibular system damage patients multiple sclerosis ms may central peripheral origin subsequent vestibular impairments may contribute dizziness balance disorders fatigue population vestibular rehabilitation targeting vestibular impairments may improve symptoms furthermore successful tool neurological rehabilitation immersive virtual reality vri also implemented within vestibular rehabilitation interventionmethods analysis protocol describes parallelarm pilot randomised controlled trial blinded assessments 30 patients ms vestibular impairment dizziness handicap inventory 16 experimental group will receive vri vestibular rehabilitation intervention based conventional cawthornecooksey protocol control group will perform conventional protocol duration intervention groups will 7 weeks 20 sessions 3 sessions week primary outcomes feasibility safety vestibular vri intervention patients ms secondary outcome measures dizziness symptoms balance performance fatigue quality life quantitative assessment will carried baseline t0 immediately intervention t1 followup period 3 6 months t2 t3 additionally order examine feasibility intervention qualitative assessment will performed t1ethics dissemination study approved andalusian review board ethics committee virgen macarenavirgen del rocio hospitals id 2148n19 25 march 2020 informed consent will collected participants wish participate research results research will disseminated publication peerreviewed scientific journalstrial registration number nct04497025pmid34810187 doi101136 bmjopen2021051478,0.0
decomposition outpatient health care spending disease novel approach using insurance claims data background decomposing health care spending disease type care age sex can lead better understanding drivers health care spending lack diagnostic coding outpatient care often precludes decomposition disease yet health insurance claims data hold variety diagnostic clues may used identify diseasesmethodsin study decompose total outpatient care spending switzerland age sex service type 42 exhaustive mutually exclusive diseases according global burden disease classification using data large health insurance provider identify diseases based diagnostic clues clues include type medication inpatient treatment physician specialization disease specific outpatient treatments examinations determine diseasespecific spending direct cluesbased indirect regressionbased spending assignmentresultsour results suggest high precision disease identification many diseases overall 81 outpatient spending can assigned diseases mostly based indirect assignment using regression outpatient spending highest musculoskeletal disorders 192 followed mental substance use disorders 120 sense organ diseases 87 cardiovascular diseases 86 neoplasms account 73 outpatient spendingconclusionsour study shows potential health insurance claims data identifying diseases diagnostic coding available diseasespecific spending estimates may inform swiss health policies cost containment priority setting,0.0
transplantation human embryonic stem cells alleviates motor dysfunction aav2htt17182q transfected rat model huntingtons disease background human embryonic stem cells hescs transplantation shown provide potential source cells neurodegenerative disease studies lead behavioral recovery lentivirus transfected toxininduced huntingtons disease hd rodent model aimed observe transplantation superparamagnetic iron oxide nanoparticle spion labeled hescs migrate neural degenerated area improve motor dysfunction aav2htt17182q transfected huntington rat modelmethodsall animals randomly allocated three groups first hd group sham group control group six weeks animals hd group sham group divided two subgroups depending animals receiving either ipsilateral contralateral hescs transplantation performed cylinder test stepping test every two weeks aav2htt17182q injection hescs transplantation stem cell tracking performed per two weeks using t2 t2weighted images 47 tesla mri also performed immunohistochemistry immunofluorescence staining detect presence hescs markers huntingtin protein aggregations iron striatumresultsafter hescs transplantation htt virusinjected rats exhibited significant behavioral improvement behavioral tests spion labeled hescs showed migration hypointense signal mri cells positive iiitubulin gaba darpp32conclusioncollectively results suggested hescs transplantation can potential treatment motor dysfunction huntingtons disease,1.0
antispike igg multiple sclerosis patients bnt162b2 vaccine exploratory casecontrol study italy abstractbackground patients neuroimmunological conditions multiple sclerosis ms often receive diseasemodifying therapies dmts immunosuppressants may reduce response vaccines bnt162b2 pfizerbiontech first covid19 vaccine authorized italy clinical efficacy serological response evaluated ms patients receiving dmts immunosuppressants early multicenter study evaluated serological response bnt162b2 safety patientsmethods february 2020 enrolled consecutive ms patients treated least one dmt healthcare workers hcws received scheduled receive first dose bnt162b2 blood samples collected second vaccine dose analyzed quantitatively detect presence antispike antibodies serological response compared one control population hcws neither neuroimmunological conditions receiving immunosuppressants patients receiving treatments associated possible reduced response underscrutiny treatment group also compared undergoing treatments antispike levels described median interquartile range iqr comparisons performed wilcoxonmannwhitney test solicited unsolicited adverse events aes collectedresults 39 ms patients control population 273 hcws included one patient treatment ocrelizumab respond bnt162b2 remaining patients controls developed serological response vaccine median antispike levels similar patients 14710 bau ml iqr 7797 23570 controls 14790 bau ml iqr 8131 25280 p053 patients included underscrutiny treatments group showed reduced antispike levels 1564 bau ml iqr 334 5591 compared receiving treatments 15824 bau ml iqr 12965 22190 p0001 solicited aes mild moderate severity generally reported first days vaccination resolved following days two ms patients reported clinical relapse second vaccine doseconclusion bnt162b2 induced serological response ms patients treated dmts similar controls receiving dmts immunosuppressants treatments associated reduced levels antispike antibodies patients observations relevant implications treated patients receiving bnt162b2 community,0.0
longitudinal humoral response sarscov2 vaccination ocrelizumab treated ms patients wait repopulate abstractobjectivethe objective study measure humoral responses sarscov2 vaccination ms patients treated ocr compared ms patients without disease modifying therapies dmts relation timing vaccination bcell countmethodsocr treated patients divided early late group cutoff time 12 weeks infusion first vaccination patients vaccinated mrna1273 moderna bcells measured baseline sarscov2 antibodies measured baseline day 28 42 52 70results87 patients included 62 ocr patients 29 patients without dmts day 70 seroconversion occurred 393 ocr patients compared 100 ms patients without dmts ocr patients seroconversion varied 26 early group 50 late group 27 low bcells 56 least 1 detectable bcell l conclusionslow bcell counts prior vaccination shorter time ocr infusion vaccination may negatively influence humoral response preclude seroconversion advise ocr treated patients get first vaccination soon possible case additional booster vaccination timing vaccination based bcell count time last infusion may considered,0.0
recommendations scientific department neuroimmunology brazilian academy neurology dcni#x2f abn brazilian committee treatment research multiple sclerosis neuroimmunological diseases bctrims vaccination general specifically sarscov2 patients demyelinating diseases central nervous system abstract scientific department neuroimmunology brazilian academy neurology dcni abn brazilian committee treatment research multiple sclerosis neuroimmunological diseases bctrims provide recommendations document vaccination population demyelinating diseases central nervous system cns infections general severe acute respiratory syndrome coronavirus 2 sarscov2 causes covid19 emphasize seriousness current situation view spread covid19 country therefore reference guides vaccination clinicians patients public health authorities particularly important prevent infectious diseases dcni abn bctrims recommend patients cns demyelinating diseases eg ms nmosd continually monitored updates vaccination schedule especially beginning change treatment disease modifying drug dmd also important note vaccines safe physicians encourage use patients clearly special care taken live attenuated viruses involved finally important physicians verify dmd patient receiving last dose taken drug may affect induction immune response differently,1.0
translation cultural validation revised illness perception questionnaire healthcare professionals brazilian portuguese abstract background multiple sclerosis progression disability can rated differently healthcare professionals therefore physicians perceive disease can impact treatment decisions previous studies matter objective translate transculturally validate revised illness perception questionnaire healthcare professionals ipqr hp use brazilian portuguese methods process used validate ipqr hp based steps presented guide proposed dorcas beaton final version ipqr hp 38 questions divided seven different dimensions assess patientnulls disease also two clinical cases representative reallife patients multiple sclerosis ms assembled consider two main profiles disease applied questionnaire neurologists federal university paulo unifesp assess perception ms doctors also answered brief survey establish profile interviewees statistical analysis used bayesian cfa models kappa statistics conclusions kappa statistics showed general agreement 04 bayesian cfas sevenfactor correlation solution poor fit case 1 95 confidence interval ranging 52893 273797 ppp 0107 regarding case 2 model converge even 50 000 iterations indicated specified model ie sevenfactor correlation solution case 2 inadmissible thus ipqr hp questionnaire brazilian portuguese validated,0.0
ganab novel biomarker multiple sclerosis correlation neuroinflammation ifi35 pharmaceuticals basel 2021 nov 21 14 11 1195 doi 103390 ph14111195abstractmultiple sclerosis ms still lacks reliable biomarkers neuroinflammation predictive disease activity treatment response thus prospective study assessed 55 ms patients 28 interferon ifn treated 10 treated noifn therapies 17 untreated 20 matched healthy controls hcs putative correlation densitometric expression glucosidase ii alpha subunit ganab clinical paraclinical parameters interferoninduced protein 35 ifi35 also assessed disease progression terms rio score rs order distinguish responder patients ifn therapy rs 0 nonresponder ones rs 1 found ganab 251fold downregulated ifntreated group respect untreated one p 00001 339fold downregulated responder patients compared nonresponders p 00001 ganab correlated directly rs r 08088 p 00001 lesion load ll r 05824 p 00014 ifntreated group inversely disease duration dd r 06081 p 00096 untreated one lower mean values expressed ganab ifi35 ifn responder p 00001 higher mean values nonresponder patients p 00022 inverse correlations also expressed ifi35 overall patient population r 06468 p 00001 conclusion modular expression ganab reflects ifi35 rs dd ll values making biomarker neuroinflammation predictive disease activity treatment response mspmid34832977 doi103390 ph14111195,0.0
response treatment nmosd australasian experience abstractbackground neuromyelitis optica spectrum disorder nmosd associated significant morbidity mortality several therapies recommended nmosd recently clinical trials demonstrated efficacy three monoclonal antibody therapies present retrospective observational study treatment response nmosdmethods retrospective unblinded observational study treatment efficacy rituximab traditional immunosuppressive therapy patients aqp4 antibody positive nmosd treatment efficacy assessed using annualised relapse rates arr time first relapse expanded disability status scale edss scoresresults complete relapse treatment data available 43 68 63 aqp4 antibody positive nmosd cases covering 74 episodes treatment time first relapse analysis rituximab showed risk ratio 023 95 ci 008 065 compared treatment nonsignificant reduction arr 35 compared pretreatment interferon p00002 cyclophosphamide p00034 associated increased arr compared pretreatment rituximab median 40 range 00 70 p0042 traditional immunosuppressive therapy median 40 range 00 80 p0016 associated lower final edss compared interferon median 60 range 40 75 conclusions data provide additional support use rituximab preference traditional immunosuppressive agents ms disease modifying therapies first line treatment nmosd,0.0
clinical characteristics patients pulmonary hypertension combined obstructive sleep apnoea abstractobjectiveobstructive sleep apnoea osa one cause pulmonary hypertension ph can also emerge along ph clinical diagnosis treatment osa patients ph still controversial purpose clinical observation study observe summarize incidence clinical characteristics osa patients ph explore possible predictors ph combined osamethodspatients ph diagnosed right heart catheterization underwent overnight cardiorespiratory monitoring december 2018 december 2020 enrolled osa defined apnoeahypopnoea index 5 h 50 apnoeic events obstructive baseline clinical characteristics parameters collected compare ph patients without osa logistic regression analysis run determine risk factors osa ph patientsresultsa total 35 25 140 patients osa osa relatively frequent patients ph especially patients chronic thromboembolic pulmonary hypertension patients lung disease hypoxiaassociated ph patients osa mostly male higher age lower daytime arterial oxygen pressure logistic regression analysis found older age male sex lower daytime arterial blood oxygen pressure correlated osa ph patientsconclusionosa common patients ph lower daytime arterial oxygen pressure risk factor osa older male patients ph,0.0
transition cannabis mainstream australian healthcare framings professional medical publications background medicinal cannabis legalised use range specified medical conditions australia since 2016 however nature government regulations subsequent complexity prescribing well doctors safety uncertainties stigma plant remain contributing barriers patient access media representations can offer insights nature discourse new medical products therapies ideas understandings social phenomena become constructed focusing professional medical publications study sought investigate medicinal cannabis represented professional medical publicationsmethodsusing content analysis approach investigated articles medicinal cannabis 2000 end 2019 medical journal australia australian doctor medical observer australian journal general practice australian family physician australian medicine articles coded according article type framings cannabis headline article tone key sources used article also used manifest textual analysis search word frequencies specific conditions referred articles retrievedresultsa total 117 articles retrieved analysis majority news stories physician audience across longitudinal period found reports carried positive tone towards medicinal cannabis cannabis frequently framed legitimate therapeutic option complex prescribe access strong evidence base support use also carries safety concerns time outlook cannabis research data largely positive primary sources frequently used reports peerreviewed journals government reports voices medical associations foundations well government university researchers chronic pain pain conditions frequently mentioned articles cannabis followed epilepsy cancer cancer pain nausea chemotherapyconclusionsthis analysis offers evidence medicinal cannabis framed valid medicine advocated community potential addressing range conditions despite lack evidence medicine free risk,0.0
factors contributing csf nfl reduction time starting treatment multiple sclerosis observational study abstractbackground multiple sclerosis ms neurofilament light chain nfl marker neuronal damage secondary inflammation neurodegeneration nfl levels drop commencement diseasemodifying treatment especially highly active ones however factors influence drop unknownobjective examine patient treatmentrelated factors influence csf nfl starting treatmentmethods eligible patients across two centres two csf nfl measurements clinical mri data included part observational cohort studyresults data available 61 patients 40 untreated first csf sampling t1 treated second t2 mean t1t2 19 months csf nfl reduction correlated age beta124 95ci 107 143 r2017 p0005 expanded disability status scale edss beta112 95ci 100 125 r2021 p005 type ms beta063 95ci 043 092 r2012 p0018 referencerelapsing ms treatment effect baseline nfl 702 pg ml 451 pg ml 95ci 374 509 30yearold versus 228 pg ml 95ci 63 350 60yearold association csf nfl reduction bmi disease duration sex cladribine alemtuzumabtreated patients csf nfl t2 t1 ratio correlate lymphocyte depletion rate 23 weeksconclusions observational study found factors reflecting early disease stage including younger age lower disability relapsing ms associated treatment response csf nfl factors found related including lymphopaenia highlyactive treatments,0.0
lymphomatoid papulosis patient treated glatiramer acetate glatiramoid glatopa multiple sclerosis case report j cent nerv syst dis 2021 nov 20 1311795735211053784 doi 101177 11795735211053784 ecollection 2021abstracta 48yearold caucasian woman history multiple sclerosis ms presented erythematous papulonodular lesions extremities trunk treated glatiramer acetate ga past 10 years glatiramoid glatopa 2 years prior presentation skin biopsy showed cd30+ lymphoproliferative disorder consistent lymphomatoid papulosis lyp three weeks stopping glatopa skin lesions improved remains unclear whether gas glatopas capability alter tcell differentiation may link lyp case report reminder vigilant skin lesions patients mspmid34819759 pmcpmc8606967 doi101177 11795735211053784,0.0
circsmad4 alleviates high glucoseinduced inflammation extracellular matrix deposition apoptosis mouse glomerulus mesangial cells relieving mir3773pmediated bmp7 inhibition background diabetic nephropathy dn common complication diabetes mellitus accumulating studies suggest deregulation circular rna circrna involved dn pathogenesis study aimed investigate role circsmad4 dn modelsmethodsmice treated streptozotocin establish dn models vivo mouse glomerulus mesangial cells sv40mes13 treated high glucose establish dn models vitro expression circsmad4 mir3773p bone morphogenetic protein 7 bmp7 mrna measured quantitative realtime pcr qpcr releases inflammatory factors examined elisa protein levels fibrosisrelated markers apoptosisrelated markers bmp7 checked western blot cell apoptosis monitored flow cytometry assay predicted relationship mir3773p circsmad4 bmp7 validated dualluciferase reporter assay pulldown assayresultscircsmad4 poorly expressed dn mice hgtreated sv40mes13 cells hg induced sv40mes13 cell inflammation extracellular matrix ecm deposition apoptosis circsmad4 overexpression alleviated circsmad4 knockdown aggravated hginduced sv40mes13 cell injuries mir3773p targeted circsmad4 mir3773p enrichment partly reversed effects circsmad4 overexpression bmp7 target mir3773p circsmad4 regulated bmp7 expression targeting mir3773p mir3773p overexpression aggravated hginduced injuries suppressing bmp7conclusioncircsmad4 alleviates hginduced sv40mes13 cell inflammation ecm deposition apoptosis relieving mir3773pmediated inhibition bmp7 dn progression,0.0
developmental endothelial locus1 potential biomarker incidence acute exacerbation patients chronic obstructive pulmonary disease background despite high disease burden chronic obstructive pulmonary disease copd risk acute copd exacerbation copd biomarkers available developmental endothelial locus1 del1 proposed possess beneficial effects including antiinflammatory effects hypothesized del1 blood biomarker copdobjectiveto elucidate role plasma del1 biomarker copd terms pathogenesis predicting acute exacerbationmethodscigarette smoke extract cse saline intratracheally administered wildtype wt del1 knockout ko c57bl 6 mice subsequently lung sections obtained quantify degree emphysema using mean linear intercept mli additionally plasma del1 levels compared copd noncopd participants recruited ongoing prospective cohorts using negative binomial regression analysis association plasma del1 level subsequent acute exacerbation risk evaluated patients copdresultsin vivo study del1 ko induced emphysema ko saline vs wt saline p 0003 augmented cseinduced emphysema ko cse vs wt cse p 0001 29 mice among 537 participants patients copd presented plasma log del1 levels lower noncopd participants p 004 especially noncopd never smokers p 0019 12 03 years patients copd lowest quartile log del1 demonstrated increased risk subsequent acute exacerbation compared highest quartile log del1 adjusted incidence rate ratio 364 95 confidence interval 103129 conclusionlow del1 levels associated copd development increased risk subsequent copd acute exacerbation del1 can useful biomarker patients copd,0.0
correlational study weifuchun clinical effect intestinal flora precancerous lesions gastric cancer background weifuchun wfc chinese herbal prescription consisting red ginseng isodon amethystoides fructus aurantii commonly used china treat variety chronic stomach disorders aim paper determine effect wfc intestinal microbiota changes precancerous lesions gastric cancer plgc patientsmethodsplgc patients h pylori negative randomly divided two groups received either wfc tablets dose 144 g three times day vitacoenzyme vit tablets dose 08 g three times day patients treated 6 months consecutively gastroscopy histopathology used assess histopathological changes gastric tissues treatment 16s rrna gene sequencing carried assess effects wfc intestinal microbiota changes plgc patients receiver operating characteristics roc analysis used assess sensitivity specificity different intestinal microbiota distinguishing plgc patients healthy control groupresultsgastroscopy histopathological results indicated wfc improve pathological condition plgc patients especially case atrophy intestinal metaplasia results 16s rrna gene sequencing indicated wfc regulate microbial diversity microbial composition abundance intestinal microbiota plgc patients following wfc treatment relative abundance parabacteroides decreased wfc group compared vit group roc analysis found parabacteroides effectively distinguish plgc patients healthy individuals sensitivity 079 specificity 08conclusionswfc slow progression plgc regulating intestinal microbiota abundancetrial registration nct03814629 name registry randomized clinical trial weifuchun treatment precancerous lesions gastric cancer registered 3 august 2018retrospectively registered https registerclinicaltrialsgov nct03814629,0.0
effects selfmanagement interventions depressive symptoms adults chronic physical disease s experiencing depressive symptomatology systematic review metaanalysis background chronic diseases leading cause death worldwide estimated 20 adults chronic physical diseases experience concomitant depression increasing risk morbidity mortality low intensity psychosocial interventions selfmanagement part recommended treatment however systematic review evaluated effects depression selfmanagement interventions population primary objective examine effect selfmanagement interventions reducing depressive symptomatology adults chronic disease s cooccurring depressive symptoms secondary objectives evaluate effect interventions improving psychosocial physiological outcomes eg anxiety glycemic control assess potential differential effect based key participant intervention characteristics eg chronic disease provider methodsstudies comparing depression selfmanagement interventions control group identified systematic searches databases june 2018 medline 1946 embase 1996 psycinfo 1967 cinahl 1984 b secondary snowball search strategies methodological quality included studies critically reviewed screening titles abstracts full texts eligibility assessed independently two authors data extracted one author verified secondresultsfifteen studies retained 12 metaanalysis three descriptive review total trials included 2064 participants commonly evaluated interventions people cancer n 7 diabetes n 4 baseline 6months t1 pooled mean effect size 047 95 ci 073 021 compared control groups primary outcome depression 053 95 ci 091 015 6months t2 results also significant anxiety t1 glycemic control t2 selfmanagement skills decisionmaking taking action significant moderators depression t1conclusionselfmanagement interventions show promise improving depression anxiety concomitant chronic physical disease findings may contribute development future selfmanagement interventions delivering evidencebased care population highquality rcts needed identify sources heterogeneity investigate key intervention components,0.0
author correction methylprednisolone stimulated gene expression gilz mcl1 basal cortisol levels multiple sclerosis patients relapse associated clinical response sci rep 2021 nov 19 11 1 22940 doi 101038 s41598021024158no abstractpmid34799697 doi101038 s41598021024158,0.0
highfrequency oscillations detected electroencephalography biomarkers evaluate treatment outcome mirror pathological severity predict susceptibility epilepsy abstracthighfrequency oscillations hfos electroencephalography eeg extensively investigated potential biomarker epileptogenic zones understanding role hfos epilepsy advanced considerably past decade use scalp eeg facilitates recordings hfos hfos initially applied large scale epilepsy surgery now utilized applications review summarize applications hfos 3 subtopics 1 hfos biomarkers evaluate epilepsy treatment outcome 2 hfos biomarkers measure seizure propensity 3 hfos biomarkers reflect pathological severity epilepsy nevertheless knowledge regarding clinical applications hfos remains limited present validation prospective studies required reliable application clinical management individual epileptic patients,0.0
hospitalisation events people chronic kidney disease component multimorbidity parallel cohort studies research routine care settings background chronic kidney disease ckd typically coexists multimorbidity presence 2 longterm conditions ltcs associations ckd multimorbidity hospitalisation rates known aim study examine hospitalisation rates people multimorbidity without ckd amongst people ckd aim identify risk factors hospitalisationmethodstwo cohorts studied parallel uk biobank prospective research study 20062020 secure anonymised information linkage databank sail routine care database wales uk 20112018 adults included kidney function measured baseline nine categories participants used zero ltcs one two three four ltcs excluding ckd one two three four ltcs including ckd emergency hospitalisation events obtained linked hospital recordsresultsamongst 469 339 uk biobank participants without ckd median 1 ltc ckd median 3 ltcs amongst 1 620 490 sail participants without ckd median 1 ltc ckd median 5 ltcs compared zero ltcs participants four ltcs excluding ckd high event rates rate ratios uk biobank 495 95 confidence interval 482508 sail 377 371382 higher rates ckd one ltcs rate ratios uk biobank 783 742825 sail 992 9751009 amongst people ckd risk factors hospitalisation advanced ckd age 60 multiple cardiometabolic ltcs combined physical mental ltcs complex patterns multimorbidity ltcs three body systems conclusionspeople multimorbidity high rates hospitalisation importantly rates two three times higher ckd one multimorbid conditions research needed mechanism underpinning inform strategies prevent hospitalisation highrisk group,0.0
importance cyclic cystine knot structural motif immunosuppressive effects cyclotides acs chem biol 2021 sep 30 doi 101021 acschembio1c00524 online ahead printabstractthe cyclotide t20k inhibits proliferation human immune cells currently clinical trials multiple sclerosis provide novel functional data mechanistic insights structureactivity relationships t20k analogs partial complete reduction cystine knot loss function proliferation experiments similarly acyclic analog t20k inactive lymphocyte bioassays lack activity nonnative peptide analogs appears associated ability cyclotides interact penetrate cell membranes since cellular uptake studies demonstrated fast fractional transfer native peptide cytosol human immune cells therefore structural differences cyclic linear native folded peptides investigated nmr elucidate structureactivity relationships acyclic t20k less rigid backbone considerable structural changes loops 1 6 compared native cyclic t20k supporting idea cyclic cystine knot motif unique bioactive scaffold study provides evidence structural motif cyclotides governs bioactivity interactions transport across biological membranes structural integrity peptides observations useful understand structureactivity cystine knot proteins due structural conservation cystine knot motif across evolution provide guidance design novel cyclic cysteinestabilized moleculespmid34592097 doi101021 acschembio1c00524,0.0
human endogenous retrovirus multiple sclerosis review transcriptome findings abstractmultiple sclerosis autoimmune disease unknown etiology genetic environmental factors believed trigger ms autoimmunity among environmental factors infectious agents extensively investigated human endogenous retroviruses hervs especially hervw believed associated ms pathogenesis hervs derived ancestral infections comprise around 8 human genome although hervs silenced retroviral genes may expressed virion formation extensive evidence relationship hervw ms including higher levels hervw expression ms patients hervw protein detection ms plaques hervw env protein inducing inflammatory response vitro vivo models discuss possible links hervs pathogenesis ms present new data regarding diversity hervs expression samples derived ms patients,0.0
pregnancy women ms impact longterm disability accrual nationwide danish cohort abstractbackgroundpregnancy considered influence disease course women multiple sclerosis ms objectivethe aim study investigate effect pregnancy longterm disability accrual women msmethodsthe danish multiple sclerosis registry dmsr used identify women diagnosed clinically isolated syndrome relapsingremitting ms cox models pregnancy timedependent exposure propensity score ps models used evaluate time reach confirmed expanded disability status scale edss score 4 6resultsa total 425 women became parous 840 remained nulliparous including pregnancy timedependent exposure nonsignificant association time reach edss 4 hazard ratio hr 086 95 confidence interval ci 061120 edss 6 hr 070 95 ci 040120 found correspondingly ps model showed association pregnancy time reach edss 4 hr 085 95 ci 056128 conclusionthis study concludes pregnancy affect longterm disability accumulation,0.0
recovery motor function rats complete spinal cord injury following implantation collagen#x2f silk fibroin scaffold combined human umbilical cordmesenchymal stem cells summary objective study aimed assess effect collagen silk fibroin scaffolds seeded human umbilical cordmesenchymal stem cells functional recovery acute complete spinal cord injury methods fibroin collagen mixed mass ratio 37 composite scaffolds produced forty rats randomly divided sham group without spinal cord injury spinal cord injury group spinal cord transection without implantation collagen silk fibroin scaffolds group spinal cord transection implantation collagen silk fibroin scaffolds collagen silk fibroin scaffolds + human umbilical cordmesenchymal stem cells group spinal cord transection implantation collagen silk fibroin scaffolds cocultured human umbilical cordmesenchymal stem cells motor evoked potential bassobeattiebresnahan scale modified bielschowskynulls silver staining immunofluorescence staining performed results bbb scores collagen silk fibroin scaffolds + human umbilical cordmesenchymal stem cells group significantly higher spinal cord injury collagen silk fibroin scaffolds groups p005 p001 amplitude latency markedly improved collagen silk fibroin scaffolds + human umbilical cordmesenchymal stem cells group compared spinal cord injury collagen silk fibroin scaffolds groups p005 p001 meanwhile compared spinal cord injury collagen silk fibroin scaffolds groups neurofilament positive nerve fiber ensheathed myelin basic protein positive structure injury site observed collagen silk fibroin scaffolds + human umbilical cordmesenchymal stem cells group p001 p005 results bielschowskynulls silver staining indicated nerve fibers observed lesion site collagen silk fibroin scaffolds + human umbilical cordmesenchymal stem cells group compared spinal cord injury collagen silk fibroin scaffolds groups p001 p 005 conclusion results demonstrated transplantation human umbilical cordmesenchymal stem cells collagen silk fibroin scaffolds promote nerve regeneration recovery neurological function acute spinal cord injury,1.0
anaemia cerebrospinal fluid biomarkers alzheimers pathology cognitively normal elders cable study background anaemia reported associated cognitive decline alzheimers disease ad associations anaemia cerebrospinal fluid csf ad biomarkers still unknown study aimed investigate associations anaemia csf ad biomarkersmethodsparticipants included chinese alzheimers biomarker lifestyle cable study associations anaemia severity csf ad biomarkers including amyloid 142 a42 total tau ttau phosphorylated tau ptau analysed multiple linear regression models adjusted age gender educational levels apoe 4 alleles comorbidities history coronary heart disease history stroke hypertension diabetes mellitus dyslipidaemia glomerular filtration rateresultsa total 646 cognitively normal older adults consisting 117 anaemia patients 529 nonanaemia individuals included study anaemia patients lower levels csf a42 individuals without anaemia p 0035 besides participants severe anaemia lower csf a42 levels p 0045 significant association anaemia csf ttau ptau levels foundconclusioncrosssectionally anaemia associated lower csf a42 levels findings consolidated causal close relationship anaemia ad,0.0
new report combined central peripheral demyelination case report front neurol 2021 nov 19 12730129 doi 103389 fneur2021730129 ecollection 2021abstractcombined central peripheral demyelination ccpd encountered frequently clinical practice requires high level suspicion diagnosis describe case young man diagnosed radiologically isolated syndrome ris presenting initially symptoms suggestive central nervous system cns insult form double vision slurred speech leftsided numbness unsteadiness however next day admission neurological examination remarkable ataxia areflexia ophthalmoplegia typical triad miller fisher syndrome mfs confirming diagnoses final diagnosis ccpd made challenges one may face diagnose treat ccpd urge sharing similar cases open door extensive thorough investigations encourage studies analysis available data come consolidated management guidelines rare disorderspmid34867717 pmcpmc8639527 doi103389 fneur2021730129,1.0
cuprizone feed formulation influences extent demyelinating disease pathology sci rep 2021 nov 19 11 1 22594 doi 101038 s41598021019633abstractcuprizone copperchelating agent induces pathology similar within multiple sclerosis ms lesions reliability reproducibility cuprizone inducing demyelinating disease pathology depends animals ingesting consistent doses cuprizone cuprizonecontaining pelleted feed convenient way delivering cuprizone efficacy pellets inducing demyelination questioned study compared degree demyelinating disease pathology mice fed cuprizone delivered pellets mice fed powdered cuprizone formulation early 3 week demyelinating timepoint within rostral corpus callosum cuprizone pellets effective cuprizone powder increasing astrogliosis microglial activation dna damage decreasing density mature oligodendrocytes however cuprizone powder demonstrated greater protein nitration relative controls furthermore mice fed control powder significantly fewer mature oligodendrocytes fed control pellets caudal corpus callosum cuprizone pellets performed better cuprizone powder relative controls increasing astrogliosis microglial activation protein nitration dna damage tissue swelling reducing density mature oligodendrocytes importantly cuprizone pellets induced detectable demyelination compared controls two feeds similar effects oligodendrocyte precursor cell opc dynamics taken together data suggest demyelinating disease pathology modelled effectively cuprizone pellets powder 3 weeks combined added convenience cuprizone pellets suitable choice inducing early demyelinating disease pathologypmid34799634 doi101038 s41598021019633,1.0
b cells support repair injured tissues adopting myd88dependent regulatory functions phenotype abstractexogenously applied mature nave b220+ cd19+ igm+ igd+ b cells strongly protective context tissue injury however mechanisms b cells detect tissue injury aid repair remain elusive show distinct models skin brain injury myd88dependent tolllike receptor tlr signaling tlr2 6 tlr4 essential protective benefit b cells vivo b cellspecific deletion myd88 abrogated effect b cell response injury multimodal simultaneous production regulatory cytokines il10 il35 transforming growth factor beta tgf inflammatory cytokines tumor necrosis factor alpha tnf il6 interferon gamma cytometry analysis showed response time environmentdependent vivo 2030 applied b cells adopting immune modulatory phenotype high coexpression anti proinflammatory cytokines 1848 h injury site b cell treatment reduced expression tnf increased il10 tgf infiltrating immune cells fibroblasts injury site proteomic analysis showed b cells complex timedependent homeostatic effect injured microenvironment reducing expression inflammationassociated proteins increasing proteins associated proliferation tissue remodeling protection oxidative stress findings chart validate first mechanistic understanding effects b cells immunomodulatory cell therapy context tissue injury,0.0
effect ofatumumab versus placebo relapsing multiple sclerosis patients japan russia phase 2 apolitos study abstractbackgroundofatumumab first fully human anticd20 monoclonal antibody developed treatment relapsing multiple sclerosis rms can selfadministered homeobjectiveto investigate efficacy safety ofatumumab rms patients japan russiamethodsapolitos included 24week doubleblind placebocontrolled corepart followed openlabel extensionpart patients randomized 21 subcutaneous ofatumumab 20 mg placebo primary outcome number gadoliniumenhancing gd+ t1 lesions per scan 24 weeksresultssixtyfour patients randomized ofatumumab n 43 placebo n 21 primary endpoint met ofatumumab reduced gd + t1 lesions versus placebo 936 p 0001 results consistent across regions japan russia ofatumumab reduced annualized t2 lesion relapse rate versus placebo week 24 groups showed benefit ofatumumab extensionpart incidence adverse events lower ofatumumab versus placebo 698 vs 810 injectionrelated reactions common deaths opportunistic infections malignancies reportedconclusionofatumumab demonstrated superior efficacy versus placebo sustained effect 48 weeks rms patients japan russia switching ofatumumab 24 weeks led rapid radiological clinical benefits safety findings consistent pivotal trials,0.0
conditional deletion rock2 induces anxietylike behaviors alters dendritic spine density morphology ca1 pyramidal neurons abstractrhoassociated kinase isoform 2 rock2 attractive drug target several neurologic disorders critical barrier rock2based research therapeutics lack mouse model enables investigation rock2 spatial temporal control gene expression overcome generated rock2fl fl mice mice expressing cre recombinase forebrain excitatory neurons camkiicre crossed rock2fl fl mice cre rock2fl fl contribution rock2 behavior well dendritic spine morphology hippocampus medial prefrontal cortex mpfc basolateral amygdala bla examined cre rock2fl fl mice spent reduced time open arms elevated plus maze increased time dark lightdark box test compared littermate controls results indicated cre rock2fl fl mice exhibited anxietylike behaviors examine dendritic spine morphology individual pyramidal neurons ca1 hippocampus mpfc bla targeted iontophoretic microinjection fluorescent dye followed highresolution confocal microscopy neuronal 3d reconstructions morphometry analysis dorsal ca1 cre rock2fl fl mice displayed significantly increased thin spine density basal dendrites reduced mean spine head volume across spine types apical dendrites ventral ca1 cre rock2fl fl mice exhibited significantly increased spine length apical dendrites spine density morphology comparable mpfc bla genotypes findings suggest neuronal rock2 mediates spine density morphology compartmentalized manner among ca1 pyramidal cells absence rock2 mechanisms may contribute anxietylike behaviors,0.0
practice effects mobile tests cognition dexterity mobility patients multiple sclerosis data analysis smartphonebased observational study j med internet res 2021 nov 18 23 11 e30394 doi 102196 30394abstractbackground smartphones builtin sensors allow measuring functions diseaserelated domains mobile tests improve disease characterization monitoring potentially support treatment decisions multiple sclerosis ms multifaceted chronic neurological disease highly variable clinical manifestations practice effects can complicate interpretation improvement time potentially exaggerating treatment effects stability masking deteriorationobjective aim study identify shortterm learning longterm practice effects 6 active tests cognition dexterity mobility userscheduled highfrequency smartphonebased testingmethods analyzed data 264 people selfdeclared ms minimum 5 weeks followup least 5 repetitions per test floodlight open study selfenrollment study accessible smartphone owners 16 countries collected data openly available scientists using regression bounded growth mixed models characterized practice effects following tests electronic symbol digit modalities test esdmt cognition finger pinching draw shape dexterity two minute walk uturn static balance mobilityresults strong practice effects found esdmt n4824 trials finger pinching n19 650 draw shape n19 019 modeled boundary improvements 408 399416 862 836887 231 209252 baseline respectively half practice effect reached 11 repetitions esdmt 28 repetitions finger pinching 17 repetitions draw shape 90 reached 35 94 56 repetitions respectively although baseline performance levels highly variable across participants significant differences shortterm learning effects low performers 5th 25th percentile median performers high performers 75th 95th percentile found esdmt fifth trial 150200 small differences observed finger pinching 12525 uturn n15 051 static balance n16 797 shortterm learning effects observed ceased maximum 5 trials two minute walk n14 393 neither shortterm learning longterm practice effects observedconclusions smartphonebased tests promising monitoring disease trajectories ms chronic neurological diseases findings suggest strong longterm practice effects cognitive dexterity functions accounted identify diseaserelated changes domains especially context personalized health studies without comparator arm contrast changes mobility may easily interpreted absence longterm practice effects even though shortterm learning effects might consideredpmid34792480 doi102196 30394,0.0
role noncoding rnas parkinsons disease biomarkers associations pathogenic pathways abstractthe discovery various noncoding rnas ncrnas biological implications growing area cell biology increasing evidence revealed canonical noncanonical functions long small ncrnas including micrornas long ncrnas lncrnas circular rnas piwiinteracting rnas trnaderived fragments ncrnas ability regulate gene expression modify metabolic pathways thus may important roles diagnostic biomarkers therapeutic targets various diseases including neurodegenerative disorders especially parkinsons disease recently diverse sequencing technologies wide variety bioinformatic analytical tools reverse transcriptase quantitative pcr microarrays nextgeneration sequencing longread sequencing numerous ncrnas shown associated neurodegenerative disorders including parkinsons disease review article will first introduce biogenesis different ncrnas including micrornas piwiinteracting rnas circular rnas long noncoding rnas trnaderived fragments pros cons detection platforms ncrnas reproducibility bioinformatic analytical tools will discussed second part finally recent discovery numerous pdassociated ncrnas association diagnosis pathophysiology pd reviewed micrornas long ncrnas transported exosomes biofluids particularly emphasized,0.0
parenchymal neuroinflammatory signaling dural neurogenic inflammation migraine background pain generally concomitant inflammatory reaction site nociceptive fibers activated rodent studies suggest sterile meningeal inflammatory signaling cascade may play role migraine headache well experimental studies also suggest parenchymal inflammatory signaling cascade may report nonhomeostatic conditions brain meninges induce headache however signaling mechanisms function patients unclear debated aim discuss role inflammatory signaling migraine pathophysiology light recent developmentsbodyrodent studies suggest sterile meningeal inflammatory reaction can initiated release peptides active trigeminocervical cfibers stimulation resident macrophages dendritic mast cells inflammatory reaction might needed sustained stimulation sensitization meningeal nociceptors initial activation along ganglionic central mechanisms migraines likely cerebral origin suggested prodromal neurologic symptoms based rodent studies parenchymal inflammatory signaling cascade proposed potential mechanism linking cortical spreading depolarization csd meningeal nociception recent pet mri study using sensitive inflammation marker showed presence meningeal inflammatory activity migraine aura patients occipital cortex generating visual aura studies also suggest presence parenchymal inflammatory activity supporting experimental findings rodents parenchymal inflammatory signaling also shown activated migraine triggers sleep deprivation without requiring csd resultant transcriptional changes predisposing inadequate synaptic energy supply intense excitatory transmission thus may hypothesized neuronal stress created either csd synaptic activityenergy mismatch initiate parenchymal inflammatory signaling cascade propagating meninges converted lasting headache without auraconclusionexperimental studies animals emerging imaging findings patients warrant research gain deeper insight complex role inflammatory signaling headache generation migraine,0.0
association multiple sclerosis dietary patterns based traditional concept food nature casecontrol study iran abstractintroductionit remains matter debate whether traditional concepts regarding nature food affect development progression multiple sclerosis ms date limited studies investigated association ms dietary patterns based categories food nature hot cold balanced defined traditional medicinemethodthis casecontrol study conducted october 2019 february 2020 total 60 patients diagnosed ms within preceding 6 months referred neurology outpatient clinic included case group control group included 180 patients referred center general orthopedic surgery dietary intake assessed groups reliable valid semiquantitative food frequency questionnaire data assessed using principal component analysisresultsthe mean age participants 449 1733 years analysis showed four food patterns distinguished eigenvalue 1 namely additives coldnatured foods hot balanced foods nuts dairy legumes hot balanced starches food patterns explained 578 total varianceafter adjusting confounding factors individuals highest quartile medium quartile additives coldnatured foods elevated ms risk compared lowest quartile 721 95ci 2011238 337 95ci 1021135 respectively furthermore individuals highest quartile hot balanced foods nuts group protected ms compared lowest quartile 028 95ci 008090 moreover protective effect ms seen highest quartile hot balanced starches group relative lowest quartile 034 95ci 012098 significant association found dairy legumes risk msconclusionthis study revealed dietary patterns based traditional concept food nature might associated risk developing ms represents first work area research recommended,0.0
mri prognostic factors multiple sclerosis neuromyelitis optica spectrum disorder myelin oligodendrocyte antibody disease front neurol 2021 nov 18 12679881 doi 103389 fneur2021679881 ecollection 2021abstractseveral mri measures developed last couple decades providing number imaging biomarkers can capture complexity pathological processes occurring multiple sclerosis ms brains measures provided specific information heterogeneous pathologic substrate msrelated tissue damage able detect quantify evolution structural changes within outside focal lesions clinical practise mri increasingly used ms field help assess patients followup guide treatment decisions importantly predict disease course moreover process identifying new effective therapies ms patients supported use serial mri examinations order sensitively detect subclinical effects diseasemodifying treatments earlier stage possible using measures based clinical disease activity however despite largely demonstrated relapsing forms ms poor understanding underlying pathologic mechanisms leading either progression tissue repair ms well lack sensitive outcome measures progressive phases disease repair therapies makes development effective treatments big challenge finally role mri biomarkers monitoring disease activity assessment treatment response inflammatory demyelinating diseases central nervous system neuromyelitis optica spectrum disorder nmosd myelin oligodendrocyte antibody disease mogad still marginal advanced mri studies shown conflicting results background review focused recently developed mri measures sensitive pathological changes best contribute future provide prognostic information monitor patients ms inflammatory demyelinating diseases particular nmosd mogadpmid34867701 pmcpmc8636325 doi103389 fneur2021679881,1.0
ifnar1 gene mutation may contribute developmental stuttering chinese population background developmental stuttering common form stuttering without apparent neurogenic psychogenic impairment recently wholeexome sequencing wes suggested promising approach study mendelian disordersmethodshere describe application wes identify gene potentially responsible persistent developmental stuttering pds sequencing dna samples 10 independent pds families 11 sporadic cases sanger sequencing performed verification samples obtained 73 additional patients sporadic casesresultswe first searched cosegregating variants candidate genes chinese family family 0 sequencing dna obtained 3 affected members 3 controls next sequenced dna samples obtained 9 additional chinese families families 19 stuttering verify identified candidate genes intriguingly found two missense variants leu552pro lys428gln interferonalpha beta receptor 1 ifnar1 cosegregated stuttering three independent families families 0 5 9 moreover found two additional mutations gly301glu pro335del ifnar1 gene 4 patients sporadic cases using wes sanger sequencing receptor mutagenesis cell signaling studies revealed ifnar1 variants may impair activity type ifn signalingconclusionour data indicate ifnar1 might potential pathogenic gene pds chinese population,0.0
signaling s1ps1pr axis gut immune central nervous system multiple sclerosis implication pathogenesis treatment cells 2021 nov 18 10 11 3217 doi 103390 cells10113217abstractsphingosine 1phosphate s1p signaling molecule complex biological functions exerted activation sphingosine 1phosphate receptors 15 s1pr15 s1pr expression necessary cell proliferation angiogenesis neurogenesis importantly egress lymphocytes secondary lymphoid organs since inflammatory process key element immunemediated diseases including multiple sclerosis ms s1pr modulators currently used ameliorate systemic immune responses ubiquitous expression s1prs immune intestinal neural cells significant implications regulation gutbrain axis dysfunction bidirectional communication system may significant factor contributing ms pathogenesis since impaired intestinal barrier lead interaction immune cells microbiota potential initiate abnormal local systemic immune responses towards central nervous system cns appears secondary mechanisms s1pr modulators affecting gut immune system intestinal barrier directly cns coordinated promote therapeutic effects scope review focus s1ps1pr functions cells cns gut immune system particular emphasis immunologic effects s1pr modulation implication mspmid34831439 doi103390 cells10113217,0.0
aggregation intrinsic structural disorder dipeptide repeat peptides c9orf72related amyotrophic lateral sclerosis frontotemporal dementia characterized nmr j phys chem b 2021 nov 9 doi 101021 acsjpcb1c08149 online ahead printabstractdipeptide repeats dprs known play important roles c9orf72related amyotrophic lateral sclerosis als frontotemporal dementia ftd studies dprs reported kinetics aggregation toxicity lowresolution morphology aggregates peptides dipeptide hexarepeats glypro gp 6 shown nonaggregating glyala ga 6 glyarg gr 6 exhibited formation neurotoxic aggregates however structural studies dprs elusive study explored feasibility highresolution monitoring realtime aggregation peptides solution using nmr experiments although gp 6 disordered nonaggregating existence cis trans conformations observed nmr spectra remarkable gr 6 exhibited formation multiple conformations whereas hydrophobic lowsoluble ga 6 aggregated fast temperaturedependent manner results demonstrate feasibility monitoring minor conformational changes highly disordered peptides aggregation kinetics formation small molecular weight aggregates solution nmr experiments ability detect cis trans local isomerizations gp 6 noteworthy valuable study intrinsically disordered proteins peptides nmr early detection minor conformational changes valuable better understanding mechanistic insights formation toxic intermediates development approaches inhibit potentially aid development compounds treat devastating c9orf72related als ftd diseasespmid34751579 doi101021 acsjpcb1c08149,0.0
international headache congress ihs ehf joint congress 2021 late breaking abstracts n,0.0
depression readmission risk elevated multiple sclerosis compared chronic illnesses abstractobjectiveassess readmissions depression suicide attempt sa ms admission versus chronic inflammatory illnessesmethodsthis retrospective cohort study identified ms asthma rheumatoid arthritis ra depression sa 2013 national readmissions database international classification diseases codes index admissions ms n7698 asthma n93 590 ra n3685 depression sa readmission rates analyzed hazard ratios hrs estimated 1year depression sa readmission hazard comparing ms asthma ra adjusting age sex psychiatric comorbidity substance abuse tobacco use income index hospitalization characteristicsresultsms baseline depression 247 versus asthma 156 ra 146 ninetyday depression readmission rate higher ms 05 asthma 03 ra 003 depression readmission hr higher ms admission versus asthma hr137 95 confidence interval ci 100186 p00485 ra hr468 95 ci1601362 p00047 hr different sa readmission across groups depression readmission hr double ms patients psychiatric disease substance abuse versus ra asthma patients either comorbidityconclusiondepression readmission risk ms hospitalization elevated versus asthma ra substance use baseline psychiatric comorbidity strongly associated depression readmission ms patients,0.0
repair progressive retinal detachment complicating degenerative retinoschisis surgical management outcomes phakic eyes background degenerative retinoschisis common condition defined splitting neurosensory retina may rarely associated progressive retinal detachment rd aim describe anatomic functional outcomes surgical treatment progressive symptomatic retinal detachment complicating degenerative retinoschisis psrdcr using pars plana vitrectomy ppv scleral buckle sb combined ppv sb proceduremethodsa retrospective chart review patients psrdcr jan 1 2008 dec 31 2019 conducted data regarding demographics surgical approach anatomic functional outcomes collectedresultsof 4973 charts rd repair study period 36 eyes 07 retinoschisis rd 18 eyes met inclusion criteria 04 median age 54 years range 1874 eyes phakic eyes outer layer breaks olbs 16 eyes 89 identifiable inner layer breaks olbs posterior equator charts position recorded 16 eyes single surgery anatomic success ssas final anatomical success rates 66 12 18 100 respectively eyes treated ppv sb ssas rate 75 9 12 ppv sb ssas rates 66 2 3 33 1 3 respectivelyconclusionspsrdcr exceedingly rare complication degenerative retinoschisis associated ssas rate lower uncomplicated rhegmatogenous rd majority psrdcr repaired via combined ppv sb study rarity complication limits statistical support optimal surgical method prior studies role sb combined ppv psrdcr requires investigation,0.0
knockdown heterogeneous nuclear ribonucleoprotein a1 results neurite damage altered stress granule biology cellular toxicity differentiated neuronal cells eneuro 2021 oct 22eneuro0350212021 doi 101523 eneuro0350212021 online ahead printabstractheterogeneous nuclear ribonucleoprotein a1 hnrnp a1 rna binding protein rbp localized within neurons plays crucial roles rna metabolism importance neuronal functioning underscored study pathogenic features many neurodegenerative diseases neuronal hnrnp a1 mislocalized nucleus cytoplasm resulting loss hnrnp a1 function model hnrnp a1 lossoffunction sirna mediated knockdown differentiated neuro2a cells rna sequencing rnaseq followed gene ontology go analyses show hnrnp a1 involved important biological processes including rna metabolism neuronal function neuronal morphology neuronal viability stress granule sg formation confirmed several roles showing hnrnp a1 knockdown results reduction neurite outgrowth increase cell cytotoxicity changes sg formation summary findings indicate hnrnp a1 lossoffunction contributes neuronal dysfunction cell death implicates hnrnp a1 dysfunction pathogenesis neurodegenerative diseasessignificance statementhnrnp a1 plays biologically important role controlling gene expression maintaining proper cellular functioning neurons previous research shown many neurodegenerative diseases exhibit pathogenic features hnrnp a1 dysfunction whereby mislocalized homeostatic nuclear location cytoplasm resulting loss proper functioning model hnrnp a1 lossoffunction differentiated neuronal cells show contributes neuronal dysfunction cell death data important underscores importance lossoffunction models implicates hnrnp a1 dysfunction pathogenesis neurodegenerative diseasespmid34697074 doi101523 eneuro0350212021,0.0
cargo proteins extracellular vesicles potential novel therapeutics nonalcoholic steatohepatitis background extracellular vesicles evs recognized novel cellfree therapeutics nonalcoholic steatohepatitis nash remains critical health problem herein show evs pan peroxisome proliferatoractivated receptor agonistprimed induced mesenchymal stem cell pan pparimscevs unique cargo protein signatures demonstrate therapeutic function nashresultsa unique protein signatures identified pan pparimscevs nonstimulated imscevs nash mice receiving pan pparimscevs showed reduced steatotic changes ameliorated er stress mitochondiral oxidative stress induced inflammation moreover pan pparimscevs promoted liver regeneration via inhibiting apoptosis enhancing proliferationconclusionswe conclude strategy enriching unique cargo proteins evs may facilitate development novel therapeutic option nashgraphical abstract,0.0
utilisation disease modifying treatment diversity treatment pathways relapsing remitting multiple sclerosis abstractbackground minimal information utilisation ofdisease modifying treatment dmts multiple sclerosisthe appropriate safe use medicines informed utilisation studies outcomes can inform health interventions improve appropriate use medicines post marketing surveillance activities improve safetyobjective evaluate utilisation treatment patterns disease modifying treatments dmts relapsing remitting multiple sclerosis rrms methods representative sample australian pharmaceutical benefits scheme data analysed 20062016 demographics incident users trends incident prevalent users determined individual patient treatment pathways determined sequential initiation medicines two different periods 20062013 20142019 results 20 660 patients least one dispensing dmt rrms study period median age 41 years 75 female incident prevalent use increased 20 88 respectively market responsive 13 new listings dmts study period sequential treatment found 66 initiators 20062013 285 initiators 20142019 diverse treatment pathways found 278 93 unique sequences 20062013 20142019 respectivelyconclusion availability new dmts influenced initial treatment choice prevalence users individualised treatment patterns exposure multiple medicines time will challenge traditional pharmacovigilance systems,0.0
bcell depleters attenuate humoral response sarscov2 vaccines multiple sclerosis patients casecontrol study abstractbackgroundbcell depleting agents fda approved treatment rrms ocrelizumab ocr ofatumumab ofa ppms ocr case ocr prior studies raised concerns patientsnull ability form antibodies response various antigens especially sarscov2 addition emerging data shown attenuated humoral response vaccines sarscov2 objective study determine whether bcell depleters sphingosine 1phosphate s1p modulators attenuate antibody response various sarscov2 vaccines patients ms compared ms disease modifying therapies dmts methodsthis casecontrol study looking odds developing antibodies three sarscov2 vaccines pfizerbiontech moderna johnson johnson patients treated bcell depleters s1p modulators versus disease modifying therapies patients recruited comprehensive ms center methodist hospitals patients prior covid19 infection received one three vaccines tested antibodies sarscov2 spike protein labcorp semiquantitative total antibody least two weeks following final dose vaccine groups bcell s1p modulators dmt dmt compared antibody level main outcome whether humoral response detected antibody testing dichotomous antibody response tested using logistic regression models quantitative response tested using ancova adjusted covariates age sex race ms type disease duration vaccine lymphocyte count pvalues 005 considered significantresultssixtyseven patients enrolled study 17 ocr 3 ofa 12 s1p modulators 29 dmt 6 currently dmt patients received ocr ofa decreased odds forming antibodies 0031 p0001 95 ci 00030268 patients received s1p modulators decreased odds forming antibodies 0413 p0413 95 ci 028217 however analyzing antibody response continuous variable patients s1p modulators showed lower absolute levels antibodies p0024 conclusionspatients received bcell depleters within prior 6 months sarscov2 vaccination decreased odds developing antibodies compared dmts line similar research suggests bcell depleters attenuate antibody response sarscov2 vaccines although s1p modulators attenuation absolute antibody level odds negative differ dmts,0.0
associations longterm conditions upper gastrointestinal cancer incidence prospective populationbased cohort uk biobank participants j comorb 2021 nov 17 1126335565211056136 doi 101177 26335565211056136 ecollection 2021 jandecabstractbackground aims upper gastrointestinal cancers oesophageal stomach high mortality rates often diagnosed disease progressed making important identify populations greater risk upper gastrointestinal ugi cancer promote earlier diagnosis study aims determine association broad range longterm conditions ltcs incidence ugi cancersmethod prospectivebased cohort 487 798 uk biobank participants age 3773 years excluding previous ugi cancer least absolute shrinkage selection operator lasso regression used identify candidate ltcs predictors ugi cancer strength association studied using coxs regression adjusting demographics lifestyle factorsresults median followup period 86 months 598 participants developed oesophageal cancer 397 developed stomach cancer fully adjusted models participants alcohol addiction hazard ratiohr 411 95 confidence intervalci 201843 barretts oesophagus hr 568 95 ci 336958 bronchiectasis hr 272 95 ci 101731 diabetes hr 138 95 ci 106181 hiatus hernia hr 169 95 ci 116245 parkinsons disease hr 386 95 ci 160937 psoriasis eczema hr 153 95 108217 observed higher risk oesophageal cancer stomach cancer incidence higher among participants anorexia bulimia hr 886 95 ci 1206514 barretts oesophagus hr 337 95 139814 chronic fatigue syndrome hr 336 95 ci 125903 glaucoma hr 206 95 ci 116367 multiple sclerosis hr 460 95 ci 1711234 oesophageal stricture hr 104 95 ci 1467446 pernicious anaemia hr 693 95 ci 3421403 conclusion previously unrecognised ltcs may role symptom appraisal risk assessment ugi cancer primary care research explore mechanisms underpinning findings determine whether replicable populationspmid34820338 pmcpmc8606912 doi101177 26335565211056136,0.0
twominute walking test smartphone app persons multiple sclerosis validation study jmir form res 2021 nov 17 5 11 e29128 doi 102196 29128abstractbackground walking disturbances common dysfunction persons multiple sclerosis ms 2minute walking test 2mwt widely used quantify walking speed implemented smartphonebased 2mwt s2mwt ms sherpa app persons ms performing s2mwt users app instructed walk fast safely possible 2 minutes open air app records movement calculates distance walkedobjective aim study investigate concurrent validity testretest reliability ms sherpa s2mwtmethods performed validation study 25 persons relapsingremitting ms 79 healthy control hc participants hc group 21 participants matched persons ms based age gender education followed assessment schedule persons ms hcmatched group whereas 58 participants less intense assessment schedule determine reference values hcnormative group intraclass correlation coefficients iccs determined distance measured s2mwt distance measured using distance markers pavement s2mwt assessments iccs also determined testretest reliability derived 10 smartphone tests per study participant 3 days test interviewed 7 study participants ms regarding experiences s2mwtresults total 755 s2mwts completed adherence rate persons ms participants hcmatched group 924 425 460 calculated distance walked s2mwt average 843 m 5 sd 189 m 11 higher distance measured using distance markers n43 icc 0817 found concurrent validity s2mwt combined analysis persons ms hc participants average iccs 9 testretest reliability analyses s2mwt persons ms participants hcmatched group 0648 sd 0150 0600 sd 0090 respectively whereas average icc 2 testretest reliability analyses s2mwt participants hcnormative group 0700 sd 0029 interviewed study participants found s2mwt easy perform also expressed test results can confronting pressure reach certain distance can experiencedconclusions high correlation s2mwt distance conventional 2mwt distance indicates good concurrent validity similarly high correlations underpin good testretest reliability s2mwt conclude s2mwt can used measure distance persons ms walk 2 minutes outdoors near home clinical studies clinical practice can benefitpmid34787581 doi102196 29128,0.0
hounsfield unit value ct predictor cage subsidence following standalone oblique lumbar interbody fusion treatment degenerative lumbar diseases background investigate correlation vertebral hounsfield unit hu values cage subsidence patients treated standalone sa olifmethodsa retrospective review collected data performed 76 patients underwent sa olif utilized hu value lumbar bone mineral density bmd obtained preoperative ct vertebral hu values patients subsidence compared without subsidence correlation cage subsidence clinical score investigatedresultssixteen patients 211 least radiographic evidence interbody cage subsidence average cage subsidence 25 13 mm range 0948 mm significant differences sex bmi preoperative diagnoses fused level p 005 however significant differences cage subsidence group nonsubsidence group age average lowest tscore average hu value including l1 vertebrae l1l4 horizontal plane l1l4 sagittal plane p 005 average hu value l1l4 horizontal plane showed predictable auc 0909 95 ci 08340984 p 0001 compared average lowest tscore following auc 0791 95 ci 06740909 p 0001 based logistic regression analysis average hu value l1l4 horizontal plane 0912 95 ci 08610966 p 0002 independent factor influencing cage subsidenceconclusionspatients lower average hu values lumbar vertebrae much higher risk developing cage subsidence sa olif measurement preoperative hu values preexisting ct scans rapid simple feasible,0.0
fecal microbiota transplantation protects rotenoneinduced parkinsons disease mice via suppressing inflammation mediated lipopolysaccharidetlr4 signaling pathway microbiotagutbrain axis background parkinsons disease pd prevalent neurodegenerative disorder displaying wellknown motor deficits also gastrointestinal dysfunctions consistently increasingly evident gut microbiota affects communication gut brain pd pathogenesis known microbiotagutbrain axis approach reestablishing normal microbiota community fecal microbiota transplantation fmt exerted beneficial effects pd recent studies study established chronic rotenoneinduced pd mouse model evaluate protective effects fmt treatment pd explore underlying mechanisms also proves involvement gut microbiota dysbiosis pd pathogenesis via microbiotagutbrain axisresultswe demonstrated gut microbiota dysbiosis induced rotenone administration caused gastrointestinal function impairment poor behavioral performances pd mice moreover 16s rna sequencing identified increase bacterial genera akkermansia desulfovibrio fecal samples rotenoneinduced mice contrast fmt treatment remarkably restored gut microbial community thus ameliorating gastrointestinal dysfunctions motor deficits pd mice experiments revealed fmt administration alleviated intestinal inflammation barrier destruction thus reducing levels systemic inflammation subsequently fmt treatment attenuated bloodbrain barrier bbb impairment suppressed neuroinflammation substantia nigra sn decreased damage dopaminergic neurons additional mechanistic investigation discovered fmt treatment reduced lipopolysaccharide lps levels colon serum sn thereafter suppressing tlr4 myd88 nfb signaling pathway downstream proinflammatory products sn colonconclusionsour current study demonstrates fmt treatment can correct gut microbiota dysbiosis ameliorate rotenoneinduced pd mouse model suppression inflammation mediated lpstlr4 signaling pathway gut brain possibly plays significant role prove rotenoneinduced microbiota dysbiosis involved genesis pd via microbiotagutbrain axis video abstract,0.0
short quality life scale crosscultural validation iranian patients multiple sclerosis abstracthealthrelated quality life hrqol prioritized measure multiple sclerosis ms patients short quality life scale sqol developed devy et al 2013 msspecific abbreviated scale ten items suitable routine medical care settings current study reported crosscultural validation scale persian language total 455 convenient ms patients mean age 3839 928 ranged 18 64 filled primary measure validating measures including hospital anxiety depression scale visual analogue scale quality life single index number pastyear ms relapse confirmatory factor analysis original structure indicated acceptable model fit however modestly modified structure composing physicalfunctional dimension items #13 mental dimension items #58 pain energy dimension items 4 910 also exposed sound fit meaningful structure overall internal consistency reliability sound 088 concurrent validity confirmed persian short quality life scale psqol first translated validated version scale surfacing significant implications crosscultural investigations recommended reexamine current findings classic recent suggestions concerning close interplay immunity system psychological system implications based irannulls context discussed,0.0
associations lifestyle behaviors quality life differ based multiple sclerosis phenotype j pers med 2021 nov 17 11 11 1218 doi 103390 jpm11111218abstractmultiple sclerosis ms neuroinflammatory disorder occurs nonprogressive progressive phenotypes forms present diverse symptoms may reduce quality life qol adherence healthy lifestyle behaviors associated higher qol people ms whether associations differ based ms phenotype unknown crosssectional selfreported observational data 1108 iconquerms participants analysed associations lifestyle behaviors qol assessed linear regression phenotype differences via moderation analyses diet wellness physical activity vitamin d omega3 supplement use associated qol specifically certain diet types negatively associated qol relapsingremitting ms rrms positively associated progressive ms progms participation wellness activities mixed associations qol rrms associated progms physical activity positively associated qol rrms progms phenotype differences observed diet wellness physical qol physical activity qol subdomains findings show lifestyle behaviors associated qol appear differ based ms phenotype future studies assessing timing duration adherence adopting lifestyle behaviors may better inform role ms managementpmid34834570 doi103390 jpm11111218,0.0
impact chronic mild hypoxia cerebrovascular remodelling uncoupling angiogenesis vascular breakdown background chronic mild hypoxia cmh 8 o2 stimulates robust vascular remodelling brain also triggers transient vascular disruption raises fundamental question vascular leak unwanted sideeffect angiogenic remodelling pathological response unrelated endothelial proliferation declining oxygen levels trigger endothelial dysfunctionmethodsto answer question mice exposed cmh 8 o2 periods 14 days brain tissue examined immunofluorescence determine type blood vessel arteriole capillary venule commonly associated endothelial proliferation vascular leak correlated tight junction protein expression vascular perfusion examined using dii data analysed using oneway analysis variance anova followed tukeys multiple comparison posthoc testresultsthe following observed 1 endothelial proliferation extravascular fibrinogen leak occurred capillaries lesser degree venules 2 much surprise endothelial proliferation extravascular fibrinogen leak never colocalized 3 interestingly however endothelial proliferation strongly associated intravascular fibrinogen staining pattern seen stable blood vessels 4 dii perfusion studies revealed angiogenic vessels adequately perfused suggesting fibrinogen retention angiogenic vessels due temporary closure vessel likely fibrinogen retained within vessel wall 5 bromodeoxyuridine brdu labelling means permanently label proliferating endothelial cells confirmed lack connection endothelial proliferation extravascular fibrinogen leak 6 contrast proliferating microglia detected within extravascular leaksconclusionstaken together findings support concept shortterm hypoxiainduced endothelial proliferation triggers transient fibrinogen deposition within walls angiogenic blood vessels overt vascular leak occurs vessels importantly endothelial proliferation extravascular fibrinogen leaks never colocalize demonstrating extravascular leak unwanted sideeffect angiogenic endothelial proliferation rather dysfunctional vascular response hypoxia occurs distinct group nonangiogenic blood vessels,0.0
common rare genetic variants contribute severe otitis media australian aboriginal population clin infect dis 2021 mar 9ciab216 doi 101093 cid ciab216 online ahead printabstractbackground goal identify genetic risk factors severe otitis media om aboriginal australiansmethods illumina omni25 beadchip imputed data compared 21 children severe om multiple episodes chronic suppurative om perforations tympanic sclerosis 370 individuals without phenotype followed functional mapping annotation fuma exome data filtered common exac_all01 putative deleterious variants influencing protein coding caddscaled scores 15 used compare 15 severe om cases 9 mild cases single episode acute om recorded 3 consecutive years rare exac_all001 variants filtered present severe om enrichr used determine enrichment genes contributing pathways processes relevant omresults fuma analysis identified two plausible genetic risk loci severe om nr3c1 pimputed_1000g362x10 6 encoding glucocorticoid receptor nrep pimputed_1000g367x10 6 encoding neuronal regeneration related protein exome analysis showed association severe om variants influencing protein coding caddscaled 15 geneset grxcr1 cdh23 lrp2 fat4 arsa eya4 enriched mammalian phenotype level 4 abnormal hair cell stereociliary bundle morphology related phenotypes ii rare variants influencing protein coding seen severe om provided genesets enriched abnormal ear lmna cdh23 lrp2 myo7a fgfr1 integrin interactions transforming growth factor signalling cell projection phenotypes including hair cell stereociliary bundles cilium assemblyconclusions study highlights interacting genes pathways related cilium structure function may contribute extreme susceptibility om aboriginal australian childrenpmid33693626 doi101093 cid ciab216,0.0
white blood cell count profiles multiple sclerosis attacks initiation acute chronic treatments sci rep 2021 nov 16 11 1 22357 doi 101038 s41598021019428abstractmultiple sclerosis ms major demyelinating disease central nervous system however exact mechanism unknown study aimed elucidate profile white blood cells wbcs acute phase ms attack sixtyfour patients ms time diagnosis 2492 age sexadjusted healthy controls hcs enrolled data regarding blood cell counts compared groups total wbc p 00001 monocyte p 00001 basophil p 00027 neutrophil p 00001 counts higher ms group hc group whereas lymphocyte eosinophil counts differ adjustments smoking status body mass index yielded results total differential wbc counts patients ms correlate counts t2 hyperintense brain lesions levels neurological disturbance summary patients ms showed elevated counts total wbcs monocytes basophils neutrophils time diagnosis however clinical relevance biomarkers context development progression ms remains unclearpmid34785750 doi101038 s41598021019428,1.0
association cognitive trajectories disability progression patients relapsingremitting multiple sclerosis neurology 2021 sep 23101212 wnl0000000000012850 doi 101212 wnl0000000000012850 online ahead printabstractbackground objectives longitudinal cognitive trajectories multiple sclerosis heterogenous difficult measure aimed identify discrete longitudinal reaction time trajectories relapsing remitting multiple sclerosis using computerized cognitive battery assess association trajectories reaction time disability progressionmethods participants serially completed computerized reaction time tasks measuring psychomotor speed visual attention working memory participants completed least three testing sessions minimum 180 days longitudinal reaction times modelled using latent class mixed models identify groups individuals sharing similar latent characteristics optimal models validated consistency baseline associations class membership tested using multinomial logistic regression interclass differences probability reaction time worsening probability 6month confirmed disability progression assessed using survival analysisresults total 460 people relapsing remitting multiple sclerosis included analysis task msreactor battery optimal model comprised 3 latent classes msreactor tasks identify group high probability reaction time slowing visual attention working memory tasks identify group participants 37 26 times likely experience 6month confirmed disability progression respectively participants classified predicted cognitive trajectories just 5 tests 64 89 accuracydiscussion latent class modelling longitudinal cognitive data collected computerized battery identified patients worsening reaction times increased risk disability progression slower baseline reaction time age disability increased assignment trajectory monitoring cognition clinical practice using computerized tests may enable detection cognitive change trajectories people relapsing remitting multiple sclerosis risk disability progressionpmid34556562 doi101212 wnl0000000000012850,0.0
multiple sclerosis children adults age matter neurology 2021 oct 4101212 wnl0000000000012866 doi 101212 wnl0000000000012866 online ahead printno abstractpmid34607920 doi101212 wnl0000000000012866,0.0
discontinuation disease modifying therapies associated disability progression regardless prior stable disease age abstractbackground multiple sclerosis ms patients stable disease course might view continued treatment unnecessary however guidelines regarding treatment discontinuation currently lackingobjective assess clinical course treatment discontinuation ms patients long disease durationmethods patients discontinued diseasemodifying treatments dmts resume treatment n216 extracted new york state ms consortium nysmsc followed across three time points average 46 years stable course defined change expanded disability status scale edss scores 10 increase edss60 05point increase edss60 baseline time 1 dmt discontinuation time 2 stable worsening ms patients later assessed dmt discontinuation time 3 additional analyses performed based disease subtype type medication age cutoff 55 edss 60results cohort 216 ms patients discontinued dmt 161 725 classified stable dmt discontinuation dmt discontinuation 53 previously stable ms patients 329 experienced disability worsening progression dwp 292 40 previously stable rrms spms respectively dwp dmt discontinuation two years dmt discontinuation rate dwp similar patients younger older 55 years 311 vs 259 respectively ms patients edss60 greater dwp compared less disabled patients remaining therapy well discontinuation 407 vs 154 p0001 396 vs 152 p0001 respectively conclusion ms patients stable disease course experience dwp treatment discontinuation clear relation age disease subtype patients edss60 higher risk dwp,0.0
longterm outcomes two firstgeneration trabecular microbypass stents istent phacoemulsification primary openangle glaucoma eightyear results background short mediumterm outcomes istent extensively studied however studies investigated longterm outcomes assessed longterm efficacy safety two istents concomitant cataract surgery glaucomatous eyes also evaluating measures disease stability using visual field optical coherence tomography oct optic nerve macula throughout 8 years followupmethodsthis longitudinal singlecenter consecutive case series included glaucomatous eyes underwent implantation two firstgeneration trabecular microbypass stents istent concomitant cataract surgery eightyear efficacy outcomes included mean intraocular pressure iop medications well surgical success eightyear safety outcomes included bestcorrected visual acuity bcva visual field mean deviation vfmd cuptodisc ratio cdr retinal nerve fiber layer rnfl thickness ganglion cellinner plexiform layer gcipl thickness adverse eventsresultsa total 62 eyes primary openangle glaucoma poag included 8 years postoperative iop reduced 26 192 39 mmhg preoperatively 142 24 mmhg p 0001 911 eyes achieved iop 18 mmhg vs 516 preoperatively 696 eyes achieved iop 15 mmhg vs 145 preoperatively 25 eyes achieved iop 12 mmhg vs 16 preoperatively medication use decreased 179 28 11 preoperatively 23 12 p 0018 surgical success 90 six eyes underwent subsequent glaucoma surgeries safety measures bcva cdr rnfl thickness gcipl thickness remained stable 8 years postoperative vfmd remained stable postoperative year 5 subsequently progressed according natural history glaucomatous diseaseconclusionsimplantation two istents concomitant cataract surgery effective safe treatment option surgerynave poag eyes evidenced significant iop medication reductions reasonable surgical success favorable safety outcomes throughout 8year followup data additionally supports efficacy combined procedure stabilizing slowing disease progression,0.0
uncertainty leukoencephalopathies case report background adultonset leukoencephalopathies group heterogeneous disorders characterized white matter abnormalities leukoencephalopathy usually encountered children report case adultonset leukoencephalopathy also explore concept uncertainty medicine discussing approach case multiple possible etiologiescase presentationa 70yearold caucasian male presented subacute onset cognitive impairment mood disturbances associated behavioral changes neuroimaging demonstrated highintensity lesions involving cerebral white matter progressive dementia cognitive decline followed multiple possible etiologies discussed based patient presentation risk factorsconclusionadultonset leukoencephalopathy can become diagnostic challenge certain approaches need developed explore uncertainty conditions improve diagnostic yield,0.0
auraptene monoterpene coumarin inhibits ltainduced inflammatory mediators via modulating nfb#x2f mapks signaling pathways evid based complement alternat med 2021 nov 16 20215319584 doi 101155 2021 5319584 ecollection 2021abstractobjective oxidative stressmediated inflammatory events involve progress several diseases asthma cancers multiple sclerosis auraptene au natural prenyloxycoumarin possesses numerous pharmacological activities antiinflammatory effects au investigated lipoteichoic acid lta induced macrophage cells raw 2647 methods expression cyclooxygenase cox2 tumor necrosis factor tnf interleukin1 il1 inducible nitric oxide synthase inos phosphorylation extracellular signalregulated kinase erk 1 2 p38 mapk cjun nterminal kinase jnk heme oxygenase ho1 p65 ib identified western blotting assay level nitric oxide measured spectrometer analysis nuclear translocation p65 nuclear factor kappa b nfb assessed confocal microscopic staining method native polyacrylamide gel electrophoresis performed perceive activity antioxidant enzyme catalase cat results au expressively reduced production cox2 tnf il1 inos expression ltastimulated cells au higher concentration 10 m inhibited erk jnk p38 phosphorylation induced lta moreover au blocked ib p65 phosphorylation p65 nuclear translocation however au pretreatment effective antioxidant ho1 expression cat activity reduced glutathione gsh nonenzymatic antioxidant ltainduced raw 2647 cellsconclusion findings study advocate au shows antiinflammatory effects via reducing nfb mapks signaling pathwayspmid34824589 pmcpmc8610650 doi101155 2021 5319584,0.0
association age onset gray matter volume white matter microstructural abnormalities people multiple sclerosis neurology 2021 oct 4101212 wnl0000000000012869 doi 101212 wnl0000000000012869 online ahead printabstractobjective investigate whether age onset influences brain gray matter volume gmv white matter wm microstructural abnormalities adult multiple sclerosis ms patients given influence clinical phenotype disease coursemethod hypothesisdriven crosssectional study enrolled 67 pediatriconset ms poms patients 143 sex disease duration dd matched randomlyselected adultonset ms aoms patients together 208 healthy controls subjects underwent neurological evaluation 3t mri acquisition mri variables standardized based healthy controls remove effects age sex associations dd poms aoms patients studied linear models time reach clinical mri milestones assessed productlimit approachresults dd1 year gmv wm fractional anisotropy fa abnormal aoms poms patients significant interaction age onset poms vs aoms association dd found gmv wm fa crossing point regression lines poms aoms patients 20 years dd gmv 14 wm fa poms aoms patients median dd 29 19 years reach expanded disability status scale3 p0001 31 26 years reach abnormal paced auditory serial addition task3 p001 24 18 years reach abnormal gmv p004 19 17 years reach abnormal wm fa p036 conclusions younger patients initially resilient msrelated damage compensatory mechanisms start failing loss wm integrity followed gm atrophy finally disabilitypmid34607928 doi101212 wnl0000000000012869,0.0
expansion myeloidderived suppressor cells contributes metabolic osteoarthritis subchondral bone remodeling background osteoarthritis oa subsequent acute joint injury accounts significant proportion arthropathies myeloidderived suppressor cells mdscs heterogeneous population myeloid progenitor cells classically known potent immunesuppressive activity however mdscs can also differentiate osteoclasts addition population known expanded metabolic disease objective study determine role mdscs context oa pathophysiologymethodsin study examined differentiation functional capacity mdscs become osteoclasts vitro vivo using mouse models oa mdsc quantitation humans oa pathology relative obesity statusresultswe observed mdscs expanded mice humans obesity mdscs expanded peripheral blood oa subjects relative body mass index mice fed highfat diet hfd compared mice fed lowfat diet lfd mice monocytic mdsc mmdsc expanded dietinduced obesity dio expansion destabilization medial meniscus dmm surgery induce posttraumatic oa ptoa compared shamoperated controls mmdscs dio mice greater capacity form osteoclasts culture increased subchondral bone osteoclast number humans observed expansion mmdscs peripheral blood synovial fluid obese subjects compared lean subjects oaconclusionthese data suggest mdscs reprogrammed metabolic disease potential contribute towards oa progression severity,0.0
clinical demographic characteristics male ms patients included national registry relevarem sex phenotype make difference association poor prognosis abstractbackground multiple sclerosis demographics wellknown female prevalence male patients less specifically evaluated clinical studies though clinical differences reported sexesobjective objective study assess clinical demographic differences male female patients included national argentine ms registry relevaremmaterial methods study observational retrospective based data 3 099 ms patients included 04 april 2021 statistical analysis plan included bivariate analyses crude data also adjustment ms phenotype categorized progressiveonset ms relapsingonset ms adjusted analysis mantelhaenszel odds ratio compared crude odds ratio account phenotype confounderresults data 1 074 347 men 2 025 653 women ms diagnosis analysed males presented primary progressive disease two times often women 11 5 respectively crude analyses sex presence exclusively infratentorial lesions magnetic resonance imaging studies frequent males females adjustment ms onset phenotype difference present males relapsingonset ms p000006 similarly worse expanded disability status scale scores confirmed men relapsingonset disease phenotype adjustment p002 conclusion find statistically significant clinical demographic difference sexes progressive remitting ms phenotype specifically considered however differences found clinical phenotypes line literature highlight importance stratifying analyses sex phenotype designing ms studies,0.0
dual nadph oxidases duox1 duox2 synthesize naadp necessary ca2+ signaling t cell activation sci signal 2021 nov 16 14 709 eabe3800 doi 101126 scisignalabe3800 epub 2021 nov 16abstract figure see text pmid34784249 doi101126 scisignalabe3800,0.0
epidemiology management associated burden mental health illness atopic autoimmune conditions common infections alopecia areata protocol observational study series bmj open 2021 nov 16 11 11 e045718 doi 101136 bmjopen2020045718abstractintroduction alopecia areata aa common cause immunemediated nonscarring hair loss links aa common mental health autoimmune atopic conditions common infections previously described remain incompletely elucidated contemporary descriptions epidemiology aa uk lackingmethods analysis retrospective study series using large populationbased cohort 52 million oxford royal college general practitioners rcgp research surveillance centre rsc database exploring four themes aa epidemiology mental health comorbidities autoimmune atopic associations common infectionsin epidemiology theme will describe incidence point prevalence aa overall age sex sociodemographic factors healthcare utilisation primary care visits secondary care referrals treatments aa will also assessed mental health theme will explore prevalence incidence mental health conditions anxiety depressive episodes recurrent depressive disorder adjustment disorder agoraphobia selfharm parasuicide people aa compared matched controls will also explore mental health treatment patterns medication psychological interventions time work unemployment rates within autoimmune atopic associations theme will examine prevalence atopic atopic dermatitis allergic rhinitis asthma autoimmune conditions crohns disease ulcerative colitis coeliac disease type 1 diabetes hashimotos thyroiditis graves disease rheumatoid arthritis psoriatic arthritis ankylosing spondylitis systemic lupus erythematosus sle polymyalgia rheumatica sjgrens syndrome psoriasis vitiligo multiple sclerosis pernicious anaemia people aa compared matched controls will also estimate incidence newonset atopic autoimmune conditions aa diagnosis within common infections theme will examine incidence common infections respiratory tract infection pneumonia acute bronchitis influenza skin infection urinary tract infection genital infections gastrointestinal infection herpes simplex herpes zoster meningitis covid19 people aa compared matched controlsethics dissemination health research authority decision tool classed study usual practice ethics approval required study approval granted rcgp rsc study approval committee results will disseminated peerreviewed publicationsobservational study registration number nct04239521pmid34785540 doi101136 bmjopen2020045718,0.0
prediction ptau#x2f a42 cerebrospinal fluid blood micrornas alzheimers disease background common biomarkers alzheimers disease ad amyloid tau detected cerebrospinal fluid csf positron emission tomography imaging however procedures invasive expensive hamper availability general population report panel micrornas mirnas serum can predict ptau a42 csf readily differentiate ad dementias including vascular dementia vad parkinson disease dementia pdd behavioral variant frontotemporal dementia bvftd dementia lewy body dlb methodsrna samples extracted participants blood ptau a42 csf examined diagnostic purposes pilot study controls 21 ad 23 followed second controls 216 ad 190 third groups controls 153 ad 151 used establish verify predictive model ptau a42 csf test applied fourth group patients different dementias controls 139 ad 155 amnestic mild cognitive impairment amci 55 vad 51 pdd 53 bvftd 53 dlb 52 assess diagnostic capacityresultsin pilot study 29 upregulated 31 downregulated mirnas ad group found dataset 2 mirnas included independent variables linear regression model sevenmicrorna panel mir1393p mir1433p mir146a5p mir4855p mir10a5p mir26b5p mir451a5p accurately predicted values ptau a42 csf datasets 3 4 applying predicted ptau a42 predictive model successfully differentiates ad controls vad pdd bvftd dlbconclusionsthis study suggests panel micrornas promising substitute traditional measurement ptau a42 csf effective biomarker ad,0.0
much needed metric defining reliable statistically meaningful change oral version symbol digit modalities test sdmt abstractbackground symbol digit modalities test sdmt recommended use clinical trials outcome studies monitor cognitive change however defining meaningful change elusive several yearsobjective present investigation aimed develop methods assessing individuallevel statistically significant change sdmt reliable change indices rcis standardized regressionbased srb equationsmethods total 219 healthy individuals completed oral version sdmt baseline 6month 1year followupresults sdmt demonstrated high reliability across time points rnulls83 86 reliable change scores 7 8 10 points 6month intervals represented statistically meaningful change 70 80 90 confidence intervals respectively 1year difference 8 10 12 statistically meaningful 70 80 90 confidence intervals respectively srb equations also provided taking account additional factors found predictive sdmt scores timeconclusion clinicians frequently denote decline 4 points sdmt meaningful results large normative sample show higher cutpoints needed demonstrate statistically significant decline individual level rcis provided 6 month one year assessment typical clinical practice trials srb equations also provided use applicable may provide precise assessment meaningful change,0.0
tgfinduced fibrosis review underlying mechanism potential therapeutic strategies eur j pharmacol 2021 sep 21174510 doi 101016 jejphar2021174510 online ahead printabstracttransforming growth factorbeta tgf plays multiple homeostatic roles regulation inflammation proliferation differentiation healing various tissues many studies demonstrated tgf stimulates activation proliferation fibroblasts result extracellular matrix deposition increased expression can result many fibrotic diseases level expression often correlated disease severity basis inhibition tgf activity great therapeutic potential treatment various fibrotic diseases pulmonary fibrosis renal fibrosis systemic sclerosis etc understanding molecular mechanism tgf signaling activity researchers able develop different strategies order modulate activity tgf antisense oligonucleotide developed target mrna tgf inhibit expression also neutralizing monoclonal antibodies can target tgf ligands v6 integrin prevent binding receptor activation latent tgf respectively soluble tgf receptors act ligand traps competitively bind tgf ligands many small molecule inhibitors developed inhibit tgf receptor cytoplasmic domain also intracellular signaling molecules peptide aptamer technology used target downstream tgf signaling summarize underlying mechanism tgfinduced fibrosis also review various strategies inhibiting tgf preclinical clinical studiespmid34560077 doi101016 jejphar2021174510,0.0
4octylitaconate dimethyl fumarate inhibit cox2 expression prostaglandin production macrophages j immunol 2021 oct 11ji2100488 doi 104049 jimmunol2100488 online ahead printabstractpgs important proinflammatory lipid mediators significance highlighted widespread efficacious use nonsteroidal antiinflammatory drugs treatment inflammation 4octyl itaconate 4oi derivative krebs cyclederived metabolite itaconate recently garnered much interest antiinflammatory agent article show 4oi limits pg production murine macrophages stimulated tlr1 2 ligand pam3csk4 decrease pg secretion due robust suppression cyclooxygenase 2 cox2 expression 4oi mrna protein levels decreased dimethyl fumarate fumarate derivative used treatment multiple sclerosis properties similar itaconate replicated phenotype observed 4oi also demonstrate decrease cox2 expression inhibition downstream pg production occurs nrf2independent manner findings provide new insight potential 4oi antiinflammatory agent also identifies novel antiinflammatory function dimethyl fumaratepmid34635585 doi104049 jimmunol2100488,0.0
prodromal frontotemporal dementia clinical features predictors progression background prodromal phase frontotemporal dementia ftd still well characterized conversion rates dementia predictors progression 1year followup currently unknownmethodsin retrospective study disease severity assessed using global cdr plus nacc ftld prodromal ftd defined reflect mild cognitive behavioural impairment relatively preserved functional independence global cdr plus nacc 05 well mild moderate severe dementia classified global cdr plus nacc 1 2 3 respectively disease progression 1year followup serum nfl measurements acquired subgroup patientsresultsof 563 participants 138 classified prodromal ftd 130 mild 175 moderate 120 severe ftd prodromal mild phases observed early increase serum nfl levels followed behavioural disturbances deficits executive functions negative symptoms apathy inflexibility loss insight predominated prodromal phase serum nfl levels significantly increased prodromal phase compared healthy controls average difference 145 95 ci 29 261 pg ml lower patients mild ftd average difference 155 95 ci 284 27 pg ml 1year followup 512 patients prodromal phase converted dementia serum nfl measurements baseline strongest predictors disease progression 1year followup 107 95 ci 103 111 p 0001 conclusionsprodromal ftd mutable stage high rate progression fully symptomatic disease 1year followup high serum nfl levels may support prodromal ftd diagnosis represent helpful marker assess disease progression,0.0
digital personal assistants smart ways assistive technology aid health wellbeing patients carers background digital health solutions assistive technologies create significant opportunities optimise effectiveness health social care delivery assistive technologies include lowtech items memory aids digital calendars hightech items like health tracking devices wearables depending type assistive devices can used improve quality life effect lifestyle improvements increase levels independence acceptance technology among patients carers depends various factors perceived skills competencies using device expectations trust reliability service evaluation explored impact pilot service redesign focused improving health wellbeing use voiceactivated device smart speaker alexa echo show 8methodsa service evaluation market research conducted pilot service redesign programme data collected via survey person telephone two focus groups patients n 44 informal carers n 7 age study participants ranged 50 90 years also participants belonged two types cohort one specifically focused diabetes range longterm health conditions multiple sclerosis dementia depression othersresultsthe device positive impact health social wellbeing users many direct indirect benefits identified patients carers positive attitudes towards using device selfreported benefits included reminders medications appointments improved adherence disease control increased independence productivity living alone device helped combat loneliness low moodconclusionthe findings study help realise potential assistive technology empowering supporting health social care especially season covid19 pandemic highlighted need remote management health use assistive technology pivotal role play sustainability health social care provision promoting shared care care provider service user evaluation can explore key drivers barriers implementing assistive technologies especially people ageing longterm health conditions,0.0
second brain connection gut microbiota composition multiple sclerosis j neuroimmunol 2021 aug 24 360577700 doi 101016 jjneuroim2021577700 online ahead printabstractgut microbiota composition may affect central nervous system cns immune function several studies recently examined possible link gut microbiota composition multiple sclerosis ms animal model experimental autoimmune encephalomyelitis eae studies agree patients ms suffer dysbiosis moreover altered proportion certain phyla bacteria detected digestive tracts patients compared healthy individuals review article gathers information research papers examined relationship gut microbiota composition ms possible mechanismspmid34482269 doi101016 jjneuroim2021577700,0.0
healthrelated quality life people multiple sclerosis oman oman med j 2021 nov 15 36 6 e318 doi 105001 omj2021109 ecollection 2021 novabstractobjectives multiple sclerosis ms disabling neurological disorder significant adverse effects patients quality life qol despite increased prevalence ms arabian gulf countries recent years study assessed impact ms healthrelated qol hrqol omani patients therefore objective study determine impact ms hrqol omani patients using validated diseasespecific selfadministered ms international qol musiqol instrumentmethods conducted descriptive crosssectional survey april december 2019 177 omani patients ms attending sultan qaboos university hospital khoula hospital oman using musiqol instrumentresults majority 514 patients poor hrqol 486 moderate hrqol found 30 years female married separated widowed divorced visual sleep problems resulted poorer hrqol scores among different hrqol components relationships healthcare system relationships family friends affected disease process results also showed psychological wellbeing coping domains musiqol questionnaires significantly reduced females compared malesconclusions understanding hrqol omanis ms provides valuable knowledge help optimize management diseasepmid34804600 pmcpmc8593230 doi105001 omj2021109,0.0
validation discrete regressionbased performance cognitive fatigability normative data paced auditory serial addition test multiple sclerosis front neurosci 2021 nov 15 15730817 doi 103389 fnins2021730817 ecollection 2021abstractcognitive fatigability objective performance decrement occurs time task requiring sustained cognitive effort although cognitive fatigability common debilitating symptom multiple sclerosis ms currently standard quantification objective study validate paced auditory serial addition test pasat discrete regressionbased normative data quantifying performance cognitive fatigability ontariobased sample individuals ms healthy controls individuals ms completed 3 2 versions pasat pasat performance measured total correct dyad percent dyad scores cognitive fatigability scores calculated comparing performance first half third task last half third results revealed 3 pasat sufficient detect impaired performance cognitive fatigability individuals ms given increased difficulty 2 version addition using halves thirds calculating cognitive fatigability scores equally effective methods detecting impairment finally discrete regressionbased norms classified similar proportion individuals ms impaired performance cognitive fatigability newly validated discrete regressionbased pasat norms provide new tool clinicians document statistically significant cognitive fatigability patientspmid34867152 pmcpmc8634595 doi103389 fnins2021730817,0.0
diseasemodifying therapies progressive multifocal leukoencephalopathy multiple sclerosis systematic review metaanalysis j neuroimmunol 2021 sep 15 360577721 doi 101016 jjneuroim2021577721 online ahead printabstractbackground high efficacy disease modifying therapies dmt management multiple sclerosis ms favorable effect relapse rate disability progression however can expose patients significant risks progressive multifocal leukoencephalopathy pml objective study aims investigate prognostic factors can determine outcome msrelated pml patients methods conducted literature review metaanalysis 194 patients 62 articles pubmed scopus embase results 194 patients 665 women 335 men 81 progression edss score least 1 point time pml diagnosis edssp group remaining patients either stable improved edss edsss group univariate analysis older age time pml diagnosis associated higher probability disability accumulation worsening edss least 1 point mean age 448 p 0046 adjusting variables age time pml diagnosis remained significant predictive variable multivariable logistic model 093 95 ci 088099 p 0037 natalizumab commonly associated dmt linked pml followed fingolimod others including dimethyl fumarate ocrelizumab alemtuzumab among different treatments used therapeutic agent found superior improving postpml edss conclusions younger age lower jcv viral load time pml diagnosis associated better outcome msassociate pml none pml therapies superior others associated favorable outcomepmid34547511 doi101016 jjneuroim2021577721,0.0
body size perceptions amp diet modification youth multiple sclerosis abstractbackground investigate perceptions pediatric multiple sclerosis ms patients regarding body size assess feasibility recruitment study diet modification unique populationmethods crosssectional study surveyed cohort 43 consecutive youth ms survey queried participant demographics clinical disease characteristics body size perception opinions diet modificationresults three quarters surveyed participants overweight obese 58 participants selfidentify single participant attempting diet time survey 88 participants indicated interest pursuing diet modification bmi category impact individualnulls willingness pursue diet intervention however obese participants willing participate diet intervention longer durationsconclusion significant proportion ms youth elevated bmi yet majority selfperception overweight obese regardless bmi youth ms interest pursuing diet modification attempts benefit disease course,0.0
factors associated treatment escalation ms care results international conjoint study abstractbackground previous studies multiple sclerosis ms showed therapeutic inertia ti affects 60 90 neurologists 25 daily treatment decisions objective study determine common factors attribute levels associated decisions treatment escalation international study ms caremethods 300 neurologists ms expertise 20 countries invited participate participants presented 12 pairs simulated ms patient profiles described 13 clinically relevant factors used disaggregated discrete choice experiments estimate weight factors attributes affecting physiciansnull decisions considering treatment selection participants asked select ideal candidate treatment escalation modest higherefficacy therapiesresults overall 229 neurologists completed study completion rate 763 top 3 weighted factors associated treatment escalation previous relapses 20 baseline expanded disability status scale edss 18 mri activity 13 patient demographics desire pregnancy modest influence 3 observed differences weight factors associated treatment escalation ms specialists nonms specialistsconclusions results provide critical information factors influencing neurologistsnull treatment decisions applied continuing medical education strategies,0.0
using patient feedback adapt intervention materials based acceptance commitment therapy people receiving renal dialysis background theorybased intervention materials must carefully adapted meet needs users specific physical conditions acceptance commitment therapy act adapted successfully cancer chronic pain diabetes irritable bowel syndrome multiple sclerosis range conditions far people receiving renal haemodialysis paper presents findings study adapt actbased intervention materials specifically renal dialysismethodsdraft written materials consisting four stories depicting fictitious individuals used actrelated techniques help overcome different challenges difficulties related dialysis adapted using systematic patient consultation process participants 18 people aged 1980 years chronic kidney disease receiving renal dialysis individual semistructured interviews conducted elicit participants views content draft materials adapted make realistic relevant people receiving renal dialysis materials presented delivered people receiving renal dialysis interview transcripts analysed using qualitative adaptation delphi method themes used framework translating feedback proposals modificationsresultsthe analysis patient feedback supported use patient stories suggested presented video narrated real dialysis patients also indicated specific adaptations make stories credible realistic participant feedback translated proposals change considered along clinical ethical theoretical factors outcome design videobased intervention separated stories individuals explanations specific act techniques provided greater structure material organised smaller chunks intervention adapted specifically people receiving renal dialysis retaining distinctive theoretical principles actconclusionsthe study shows value consulting patients development intervention materials illustrates process integrating patient feedback theoretical clinical practical considerations intervention design,0.0
lymphocyte counts multiple sclerosis therapeutics mechanisms action treatmentlimiting side effects cells 2021 nov 15 10 11 3177 doi 103390 cells10113177abstractalthough detailed pathogenesis multiple sclerosis ms completely understood broad range diseasemodifying therapies dmts available common side effect nearly every ms therapeutic agent lymphopenia can beneficial cases treatmentlimiting sound knowledge underlying mechanism action selected agent required order understand treatmentassociated changes white blood cell counts well monitoring consequences review comprehensive summary currently available dmts regard effects lymphocyte count first part describe important general information role lymphocytes course ms essentials lymphopenic states second part introduce different dmts according underlying mechanism action summarizing recommendations lymphocyte monitoring definitions lymphocyte thresholds different therapeutic regimenspmid34831400 doi103390 cells10113177,0.0
mechanisms myelin repair mri techniques therapeutic opportunities multiple sclerosis abstractmultiple sclerosis ms chronic inflammatory demyelinating disease central nervous system cns remyelination process requires activation migration differentiation oligodendrocyte progenitor cells opc demyelinated areas metabolic dysfunction chronic demyelinating lesions impairs activation opcs myelin debris clearance microglia decreases age along diminished secretion factors promoting opc differentiation conventional magnetic resonance imaging mri sequences limited ability differentiate unmyelinated remyelinated lesions advanced mri sequences based magnetization transfer ratio mtr myelin water fraction mwf diffusion tensor imaging dti used evaluate remyelination clinical trials recently qspace myelin map qmm used experimental exploratory clinical studies improvement myelinspecific mri sequences high reliability standardization among centers will allow accurate evaluation new therapies improve remyelination new remyelination promoting treatments alone combination current options may reduce risk longterm disability ms,1.0
preliminary outcomes combination demineralized bone matrix platelet rich plasma treatment long bone nonunions background variety bone graft substitutes introduced treatment bone nonunions however clinical outcomes current evidences various conflicting study aimed present preliminary outcomes treatment protocol combination demineralized bone matrix dbm platelet rich plasma prp used bone graft substitute long bone nonunionsmethodsdata retrospective study reviewed collected consecutive case series involving 43 patients presented long bone nonunion treated department october 2018 may 2019 combination dmb prp applied bone defect filler 16 patients whilst 27 patients treated iliac bone autografting patients demographics postoperative complications result bone union compared evaluatedresultsthe demographic data two groups comparable significant difference found regard incidence postoperative complications graft rejection heterotopic ossification complications noted distribution bony healing time rather scattered differ significantly groups 7533 3357 months vs 6625 2516 months p0341 union identified radiographically 15 16 patients dbm+prp group 24 27 patients autograft groupconclusionsthe present study identified low incidence postoperative complications satisfactory bony healing rate achieved treatment long bone nonunions augmented combination dbm prp although findings might indicate promising future treatment protocol larger higher quality studies also executed assess routine use,0.0
lowdose naltrexone treatment fibromyalgia protocol doubleblind randomized placebocontrolled trial background lowdose naltrexone ldn used widely offlabel treatment pain despite limited evidence effectiveness small trials high risk bias investigated effect ldn pain associated fibromyalgia women larger methodologically robust studies needed primary aim randomized controlled trial investigate 12 weeks ldn treatment superior placebo reducing average pain intensity last 7 days women fibromyalgiamethodsa singlecenter permuted block randomized doubleblind placebocontrolled parallelgroup trial will performed denmark randomization comprises 100 women aged 1864 years diagnosed fibromyalgia will treated either ldn placebo 12 weeks including 4week titration phase primary outcome change average pain intensity last 7 days baseline 12 weeks secondary outcomes fibromyalgiarelated symptoms ie tenderness fatigue sleep disturbance stiffness memory problems depression anxiety measures global assessment physical function impact fibromyalgia pain distribution healthrelated quality life intentiontotreat analysis will performed number responders 15 30 50 improvement pain 12 weeks will calculated ldn placebo groups exploratory outcomes include measures pain sensitivity muscle performance biomarkersdiscussionthis study will contribute highlevel evidence efficacy lowdose naltrexone treatment pain women fibromyalgia secondary outcomes include diseasespecific generic components investigating whether ldn influences symptoms pain explorative outcomes included provide greater insight mechanism action ldn possibly better understanding underlying pathology fibromyalgiatrial registrationeudract 201900070230 registered 12 july 2019 clinicaltrialsgov nct04270877 registered 17 february 2020,0.0
chromophobe renal cell carcinomalike thyroid carcinoma possible misdiagnosis metastatic renal cell carcinoma int j clin exp pathol 2021 nov 15 14 11 10951101 ecollection 2021abstractto date multiple thyroid cancer variants reported herein report rare case chromophobe renal cell carcinomalike thyroid carcinoma crethca 60yearold woman morphologic findings resembled chromophobe renal cell carcinoma chrcc chrcc kidney characterized large polygonal tumor cells distinct cell borders perinuclear clearing multiple binucleate cells strongly positive immunostaining paired box gene 8 pax8 carbonic anhydrase ix ca ix case thyroid gland tumor incidentally detected routine medical screening without sufficient medical information showed similar histology immunohistochemical features chrcc initially misdiagnosed metastatic chrcc additional tests including kidney computed tomography positron emission tomography revealed abnormalities patients kidney therefore diagnosed tumor crethca focal weak staining thyroid transcription factor 1 ttf1 supporting evidence primary thyroid neoplasm best knowledge second report crethca literature novel variant difficult distinguish metastatic chrcc can diagnostic challenge pathologists studies similar cases done define new entitypmid34900078 pmcpmc8661068,0.0
elevated mycobacterium avium subsp paratuberculosis map antibody titer japanese multiple sclerosis j neuroimmunol 2021 aug 25 360577701 doi 101016 jjneuroim2021577701 online ahead printabstractto investigate whether antibody production mycobacterium avium subsp paratuberculosis map related clinical characteristics multiple sclerosis ms human leukocyte antigen hla alleles igg antibody three map peptides two human peptides homologous map measured sera 103 ms patients 50 healthy controls hcs ms patients higher igg levels map2694295303 map2694igg hcs antibodies comparable multivariate analysis demonstrated higher map2694igg titers associated higher edss scores hla alleles dairy product consumption immune response map may worsen ms disabilitypmid34507015 doi101016 jjneuroim2021577701,0.0
pharmacodynamic biomarkers longterm interferon beta1a therapy reflex reflexion j neuroimmunol 2021 sep 9 360577715 doi 101016 jjneuroim2021577715 online ahead printabstractthis posthoc analysis evaluated candidate biomarkers longterm efficacy subcutaneous interferon beta1a sc ifn 1a reflex reflexion studies clinically isolated syndrome samples 507 reflex 287 reflexion study participants analyzed investigated biomarkers significantly upregulated 154fold response sc ifn 1a treatment versus baseline p 0008 validity mx1 25oas il1ra biomarkers response sc ifn 1a confirmed large patient cohort biomarkers consistently upregulated dosedependent manner neopterin trail ip10 confirmed biomarkers associated longterm sc ifn 1a treatment efficacy 5 yearspmid34536787 doi101016 jjneuroim2021577715,0.0
rare presentation undiagnosed multiple sclerosis covid19 vaccine j community hosp intern med perspect 2021 nov 15 11 6 772775 doi 101080 2000966620211979745 ecollection 2021abstractmultiple sclerosis ms autoimmune mediated neurological disorder affects central nervous system leads myelin sheath destruction pathogenesis ms involves t helper cells causing inflammation eventual death oligodendrocytes etiologies development ms include combination genetic environmental immune factors vaccines proposed increase immune response reportedly activated autoimmune disorders although certain vaccines hepatitis b associated ms studies refuted cases present rare case 32yearold patient presented symptoms suggestive ms days receiving covid vaccine laboratory imaging findings confirmed diagnosis ms started steroids discharged stable condition days afterpmid34804388 pmcpmc8604537 doi101080 2000966620211979745,1.0
new perspectives cytoskeletal dysregulation mitochondrial mislocalization amyotrophic lateral sclerosis abstractamyotrophic lateral sclerosis als progressive neurodegenerative disease characterized selective early degeneration motor neurons brain spinal cord motor neurons long axonal projections rely integrity neuronal cytoskeleton mitochondria regulate energy requirements maintaining axonal stability anterograde retrograde transport signaling neurons formation protein aggregates contain cytoskeletal proteins mitochondrial dysfunction devastating effects function neurons shared pathological features across several neurodegenerative conditions including als alzheimers disease parkinsons disease huntingtons disease charcotmarietooth disease furthermore becoming increasingly clear cytoskeletal integrity mitochondrial function intricately linked therefore dysregulations cytoskeletal network mitochondrial homeostasis localization may common pathways initial steps neurodegeneration review discuss known contributors including variants genetic loci aberrant protein activities modify cytoskeletal integrity axonal transport mitochondrial localization als overlapping features neurodegenerative diseases additionally explore emerging pathways may contribute disruption als,0.0
insights role csf1r central nervous system neurological disorders front aging neurosci 2021 nov 15 13789834 doi 103389 fnagi2021789834 ecollection 2021abstractthe colonystimulating factor 1 receptor csf1r key tyrosine kinase transmembrane receptor modulating microglial homeostasis neurogenesis neuronal survival central nervous system cns csf1r can proteolytically cleaved soluble ectodomain intracellular protein fragment supports survival myeloid cells upon activation two ligands colony stimulating factor 1 interleukin 34 csf1r lossoffunction mutations major cause adultonset leukoencephalopathy axonal spheroids pigmented glia alsp dysfunction also implicated neurodegenerative disorders including alzheimers disease ad review physiological functions csf1r cns pathological effects neurological disorders including alsp ad frontotemporal dementia multiple sclerosis understanding pathophysiology csf1r critical developing targeted therapies related neurological diseasespmid34867307 pmcpmc8634759 doi103389 fnagi2021789834,0.0
evidence subclinical disease activity progressive disease mog antibody disease neuromyelitis optica spectrum disorder j neuroimmunol 2021 aug 26 360577702 doi 101016 jjneuroim2021577702 online ahead printabstractmyelin oligodendrocyte glycoprotein antibody disease mogad aquaporin4 igg seropositive neuromyelitis optica spectrum disorder aqp4igg+ nmosd generally considered relapsing disorders without clinical progression subclinical disease activity outside clinical relapses contrast multiple sclerosis ms advances diagnosis treatment conditions prolonged periods remission without relapses can achieved question whether progressive disease courses can occur reemerged review focus studies exploring evidence relapseindependent clinical progression subclinical disease activity patients mogad aqp4igg+ nmosdpmid34547512 doi101016 jjneuroim2021577702,1.0
c3 c4 complement levels aqp4iggpositive nmosd mogad j neuroimmunol 2021 aug 24 360577699 doi 101016 jjneuroim2021577699 online ahead printabstractwhile complementdependent cytotoxicity cdc known effector mechanism aquaporin4immunoglobulin ig gpositive aqp4igg+ neuromyelitis optica spectrum disorder nmosd role cdc myelin oligodendrocyte glycoprotein antibodyassociated disease mogad less clear determined complement c3 c4 plasma concentrations patients clinically stable aqp4igg+ nmosd n 16 mogad n 15 early multiple sclerosis ms n 19 healthy controls hc n 18 c4 lower aqp4igg+ nmosd mogad ms hc p 005 pairwise comparisons c3 lower aqp4igg+ nmosd ms p 0034 findings suggest subtle complement consumption clinically stable aqp4igg+ nmosd mogadpmid34464830 doi101016 jjneuroim2021577699,1.0
detrimental relevance helicobacter pylori infection sarcopenia background helicobacter pylori h pylori gram negative microaerophilic bacteria wellknown pathogen many gastrointestinal diseases several emerging evidences suggest role numerous extragastric diseases current study investigates relationship h pylori infection sarcopenia clinical condition characterized loss mass function skeletal muscle total 3453 eligible participants third national health nutrition examination survey nhanes iii united states enrolled based serum laboratory results subjects categorized three groups normal without evidence h pylori infection antih pylori igg positive h pylori + concurrent antih pylori igg anticytotoxinassociated gene igg positive caga + sarcopenia determined skeletal muscle index smi value 1 standard deviation away mean value sexspecific healthy young adults 20 39 years old risk sarcopenia components compared subgroupsresultsodds ratios confirmed diagnosis sarcopenia higher h pylori + 2052 95 ci 16972481 p 0001 caga + 1585 95 ci 12781965 p 0001 groups moreover negative beta regression coefficient smi shown h pylori + 0023 p 0001 caga + 0017 p 0001 subanalyses categorized participants gender revealed absolute value beta regression coefficient smi higher female h pylori + subgroup 1745 male 2942 female p 0001 caga + subgroup 1407 male 2159 female p 0001 conclusionspositive serum h pylori infectious markers including antih pylori antibody caga seropositivity correlated sarcopenia low muscle quantity therefore h pylori eradication therapy may bring benefits sarcopenia patients concurrent active h pylori infection,0.0
carbohydrate lipid metabolism multiple sclerosis clinical implications etiology pathogenesis diagnosis prognosis therapy arch biochem biophys 2021 sep 10109030 doi 101016 jabb2021109030 online ahead printabstractmultiple sclerosis ms complicated autoimmune disease characterized inflammatory demyelinating events central nervous system exact etiology pathogenesis ms elucidated however set metabolic changes effects immune cells neural functions explained review highlights contribution carbohydrates lipids metabolism etiology pathogenesis ms proposed hypothetical relationship metabolic changes immune system patients ms finally potential clinical implications metabolic changes diagnosis prognosis discovering therapeutic targets discussed concluded research pathophysiological alterations carbohydrate lipid metabolism may potential strategy paving way toward ms treatmentpmid34517010 doi101016 jabb2021109030,1.0
advancing data science drug development innovative computational framework data sharing statistical analysis background novartis university oxfords big data institute bdi established research alliance aim improve health care drug development making efficient targeted using combination latest statistical machine learning technology innovative platform developed manage large volumes anonymised data numerous data sources types plan identify novel patterns clinical relevance detected humans alone identify phenotypes early predictors patient disease activity progressionmethodthe collaboration focuses highly complex autoimmune diseases develops computational framework assemble researchready dataset across numerous modalities multiple sclerosis ms project collaboration anonymised integrated phase ii phase iv clinical imaging trial data 35 000 patients across clinical phenotypes collected 2200 centres worldwide il17 project collaboration anonymised integrated clinical imaging data 30 phase ii iii cosentyx clinical trials including 15 000 patients suffering four autoimmune disorders psoriasis axial spondyloarthritis psoriatic arthritis psa rheumatoid arthritis ra resultsa fundamental component successful data analysis collaborative development novel machine learning methods rich data sets construction research informatics framework can capture data regular intervals images anonymised integrated deidentified clinical data quality controlled compiled researchready relational database available multidisciplinary analysts collaborative development group software developers data wranglers statisticians clinicians domain scientists across organisations key framework innovative facilitates collaborative data management makes complicated clinical trial data set pharmaceutical company available academic researchers become associated projectconclusionsan informatics framework developed capture clinical trial data pipeline anonymisation quality control data exploration subsequent integration database establishing framework integral development analytical tools,0.0
impact helicobacter pylorirelated metabolic syndrome parameters arterial hypertension microorganisms 2021 nov 14 9 11 2351 doi 103390 microorganisms9112351abstractarterial hypertension risk factor several pathologies mainly including cardiocerebrovascular diseases rank leading causes morbidity mortality worldwide arterial hypertension also constitutes fundamental component metabolic syndrome helicobacter pylori infection one common types chronic infection globally displays plethora gastric extragastric effects among entities helicobacter pylori implicated pathogenesis metabolic syndrome within review illustrate current stateoftheart evidence may link several components helicobacter pylorirelated metabolic syndrome including nonalcoholic fatty liver disease arterial hypertension particular current knowledge helicobacter pylori exerts virulence dietary inflammatory metabolic pathways will discussed although still causative link entities emerging evidence basic clinical research supports proposal several components helicobacter pylori infectionrelated metabolic syndrome present important risk factor development arterial hypertension triad helicobacter pylori infection metabolic syndrome hypertension represents crucial worldwide health problem pandemic scale high morbidity mortality like covid19 thereby requiring awareness appropriate management global scalepmid34835476 doi103390 microorganisms9112351,0.0
predicting clinical events using bayesian multivariate linear mixed models application scleroderma background scleroderma serious chronic autoimmune disease patients disease state manifests several irregularly spaced longitudinal measures lung heart skin organ systems threshold crossings pulmonary cardiac measures indicate potentially lifethreatening key clinical events including interstitial lung disease ild cardiomyopathy pulmonary hypertension ph statistical challenge accurately precisely predict events using clinical history patient hand reference population patientsmethodswe use bayesian mixed model approach simultaneously characterize individuals future trajectories several biomarkers estimate model using large population patients johns hopkins scleroderma center research registry joint probabilities critical lung heart events calculated byproduct mixed modelresultsthe performance approach substantially better standard common alternatives order predict individuals risks clinical setting also develop crossvalidated sequential prediction cvsp algorithm additional data observed patients visit algorithm sequentially produces updated predictions future longitudinal trajectories ild cardiomyopathy ph updated prediction distributions little additional computing example within electronic health record ehr conclusionsthis method generates realtime personalized risk estimates implemented within electronic health record system clinical testing knowledge work represents first approach compute personalized risk estimates multiple scleroderma complications,0.0
views university students jordan towards biobanking background biobanks considered primary means+ supporting contemporary research order deliver personalized precise diagnostics public acceptance participation cornerstone successaimsthis study aims assess knowledge perception attitudes towards biomedical research biobanking among students university jordanmethodologyan online questionnaire designed developed piloted divided 5 sections included questions related issues biomedical research biobanking well factors influencing decision participateresultsresponses 435 students revealed 529 previously heard biobanks overwhelming acceptance participation biomedical genetic biobanking research blood sample preferred donation protection privacy informed consent prior donation approval ethics committee trust towards researchers important factors associated willingness participate hand vagueness type research performed biospecimens unavailability general research results donor negative connotation clear agreement type informed consent preferred students contacted informed research results preferred majority students also preferred disposal biospecimens information deciding withdraw participationconclusionthere strong enthusiasm among students participate biomedical research biobanking rights reserved thus providing hope promising future jordan,0.0
exploring enablers barriers social prescribing people living longterm neurological conditions focus group investigation background people living long term neurological conditions ltncs value peer support social activities psychological support wellbeing enables manage condition social prescribing formal process referring patients link worker codesign plan improve health wellbeing intervention involves supporting participation activities based within individuals local community study aimed explore barriers enablers accessing social prescribing people living ltncs plwltncs methodsa total four focus groups carried 17 participants including different neurological conditions multiple sclerosis fragile x syndrome epilepsy traumatic brain injury two participants family carers supported people living epilepsy motor neurone disease findings analysed using thematic analysisresultsfive themes identified 1 lack knowledge 2 service provision difficulties 3 benefits social prescribing activities 4 physical barriers 5 psychological barriers lack knowledge social prescribing actually participants anticipated service provision difficulties relating funding link workers need knowledge ltncs activities varied individualised potential benefits social prescribing activities recognised across groups especially potential tackle loneliness offer plwltncs purpose participants highlighted number physical barriers transport accessibility psychological barriers anxiety stigmaconclusionsocial prescribing aims address health inequalities living longterm conditions however currently likely exclude plwltncs recommendations practice future research made,0.0
identification peptides novel inhibitors target ifn il3 tnf systemic lupus erythematosus biomed res int 2021 nov 13 20211124055 doi 101155 2021 1124055 ecollection 2021abstractautoimmune disorder chronic immune imbalance developed series pathways defect b cells t cells lack selftolerance greatly associated onset many types autoimmune complications including rheumatoid arthritis systemic lupus erythematosus sle multiple sclerosis chronic inflammatory demyelinating polyneuropathy sle autoimmune disease common type lupus causes tissue organ damage due wide spread inflammation current study twenty antiinflammatory peptides derived plant animal sources docked ligands peptides counter proinflammatory cytokines interferon gamma ifn interleukin 3 il3 tumor necrosis factor alpha tnf targeted study involved pathogenesis sle many clinical studies two docking approaches ie proteinligand docking peptideprotein docking employed study using molecular operating environment moe software haddock web server respectively amongst docked twenty peptides peptide dedtqammpfr sscore 113018 haddock score 103 25 kcal mol showed best binding interactions energy validation active amino acids ifn protein docking approaches depending upon results peptide used potential drug candidate target ifn il3 tnf proteins control inflammatory events peptides ie qepqesqq frdehkk also revealed good binding affinity ifn sscores 1098 1055 respectively similarly peptides khdrgdef frdehkk qepqesqq showed best binding interactions il3 sscores 881 864 817 respectivelypmid34812407 pmcpmc8605925 doi101155 2021 1124055,1.0
metabolic reprogramming mediates hippocampal microglial m1 polarization response surgical trauma causing perioperative neurocognitive disorders background microglial polarization toward proinflammatory m1 phenotype major contributors development perioperative neurocognitive disorders pnds metabolic reprogramming plays important role regulating microglial polarization therefore hypothesized surgical trauma can activate microglial m1 polarization metabolic reprogramming induce hippocampal neuroinflammation subsequent postoperative cognitive impairmentmethodswe used aged mice establish model pnds investigated whether surgical trauma induced metabolic reprograming hippocampus using pet ct gc tofms based metabolomic analysis determined effect glycolytic inhibitor 2deoxydglucose 2dg hippocampal microglial m1 polarization neuroinflammation cognitive function 3 d surgeryresultswe found surgery group less contextrelated freezing time either control anesthesia group p 005 without significant difference tonerelated freezing time p 005 level iba1 fluorescence intensity hippocampus significantly increased surgery group control group p 005 accompanied activated morphological changes microglia increased expression inos cd86 m1 marker enriched microglia hippocampus p 005 pet ct metabolomics analysis indicated surgical trauma provoked metabolic reprogramming oxidative phosphorylation glycolysis hippocampus inhibition glycolysis 2dg significantly alleviated surgical trauma induced increase m1 cd86+cd206 phenotype enriched microglia hippocampus upregulation proinflammatory mediators il1 il6 expression hippocampus furthermore glycolytic inhibition 2dg ameliorated hippocampus dependent cognitive deficit caused surgical traumaconclusionsmetabolic reprogramming crucial regulating hippocampal microglial m1 polarization neuroinflammation pnds manipulating microglial metabolism might provide valuable therapeutic strategy treating pnds,0.0
validation brief computerized cognitive assessment multiple sclerosis bccams comparison reference batteries abstractbackgroundthe brief computerized cognitive assessment multiple sclerosis bccams short neuropsychological battery persons multiple sclerosis pwms objectivesthe main objective study validate bccamsmethodspwms healthy subjects hs evaluated using bccams include two computerized tests computerized speed cognitive test computerized episodic visual memory test cevmt newly developed visuospatial memory test french learning test minimal assessment cognitive function ms macfims including brief international cognitive assessment multiple sclerosis bicams tests also administered regressionbased norms bccams calculated 276 hs bccams compared bicams macfims detection cognitive impairment ci resultsout 120 pwms ci detected using bccams bicams one impaired test macfims two impaired tests 591 50 379 respectively bccams produced predictive value bicams battery detecting ci macfimsconclusionthis study validated bccams validated computerized short assessment information processing speed learning ms,0.0
bashy dye platform enables fluorescence bioimaging myelin debris phagocytosis microglia demyelination cells 2021 nov 13 10 11 3163 doi 103390 cells10113163abstractmultiple sclerosis ms demyelinating disease central nervous system characterized presence demyelinated regions accumulated myelin lipid debris importantly allow effective remyelination debris must cleared microglia therefore study microglial activity sensitive tools great interest better monitor ms clinical course using boronic acidbased bashy fluorophore specific nonpolar lipid aggregates aimed address bashys ability label nonpolar myelin debris image myelin clearance context demyelination demyelinated ex vivo organotypic cultures ocscs primary microglia cells immunostained evaluate bashys colocalization myelin debris also evaluate bashys specificity phagocytosing cells additionally mice induced experimental autoimmune encephalomyelitis eae injected bashy posteriorly analyzed evaluate bashy+ microglia within demyelinated lesions indeed vitro ex vivo studies showed significant increase bashy labeling demyelinated ocscs mostly colocalized iba1expressing amoeboid phagocytic microglia importantly bashys presence also found within demyelinated areas eae mice essentially colocalizing lesionassociated iba1+ cells evidencing bashys potential vivo bioimaging myelin clearance myelincarrying microglia regions active demyelinationpmid34831386 doi103390 cells10113163,1.0
tafazzin deficiency impairs mitochondrial metabolism function lipopolysaccharide activated b lymphocytes mice abstractb lymphocytes responsible humoral immunity play key role immune response optimal mitochondrial function required support b cell activity activation examined deficiency tafazzin cardiolipin remodeling enzyme required mitochondrial function alters metabolic activity b cells response activation lipopolysaccharide mice b cells isolated 3monthold wild type tafazzin knockdown mice incubated 72h lipopolysaccharide cell proliferation expression cell surface markers secretion antibodies chemokines proteasome immunoproteasome activities metabolic function determined addition proteomic analysis performed identify altered levels proteins involved survival immunogenic proteasomal mitochondrial processes compared wild type lipopolysaccharide activated b cells lipopolysaccharide activated tafazzin knockdown b cells exhibited significantly reduced proliferation lowered expression cluster differentiation 86 cluster differentiation 69 surface markers reduced secretion immunoglobulin m antibody reduced secretion keratinocytesderived chemokine macrophageinflammatory protein2 reduced proteasome immunoproteasome activities reduced mitochondrial respiration glycolysis proteomic analysis revealed significant alterations key protein targets regulate cell survival immunogenicity proteasomal processing mitochondrial function consistent findings functional studies results indicate cardiolipin transacylase enzyme tafazzin plays key role regulating mouse b cell function metabolic activity activation modulation mitochondrial function,0.0
association vitamin d deficiency hypothyroidism results national health nutrition examination survey nhanes 20072012 abstractpurposemany smaller studies previously shown significant association thyroid autoantibody induced hypothyroidism lower serum vitamin d levels however finding confirmed largescale studies study evaluated relationship hypothyroidism vitamin d levels using large populationbased datamethodsfor study used national health nutrition examination survey nhanes years 20072012 categorized participants three clinically relevant categories based vitamin d levels optimal intermediate deficient participants also split hypothyroid hyperthyroid weighted multivariable logistic regression analyses used calculate odds hypothyroid based vitamin d statusresultsa total 7943 participants included study 614 77 hypothyroidism nearly 256 hypothyroid patients vitamin d deficiency compared 206 among normal controls adjusted logistic regression analyses showed odds developing hypothyroidism significantly higher among patients intermediate adjusted odds ratio aor 17 95 ci 1518 deficient levels vitamin d aor 16 95 ci 1419 conclusionlow vitamin d levels associated autoimmune hypothyroidism healthcare initiatives mass vitamin d deficiency screening among atrisk population significantly decrease risk hypothyroidism longterm,0.0
feasibility efficacy homebased neurofunctional exercise vs resistance exercise programs ambulatory disability multiple sclerosis patients cognitive impairment abstractbackground ambulatory disability cognitive impairment common cooccuring manifestations multiple sclerosis ms neurofunctional training specific intervention performed realistic environments may beneficial effects ambulatory disability persons ms cognitive impairment pilot sudy investigated feasibility efficacy eightweek homebased neurofunctional training hbnft program vs homebased resistance training hbrt ambulatory performance ms patients cognitive impairmentmethods thirty males females ms age 1850 years expanded disability status scale edss score 6 processing speed score 415 marker cognitive impairment randomly assigned hbnft hbrt groups one week three sessions centerbased supervised training learning programs maximizing safety participants completed eight weeks three sessions per week homebased training programs programs supported videos brochures digital video discs dvds provided clinic visits weeks 1 5 ambulatory performance tandem stance test tandem walk test timed upandgo tug sixminute walk test 6mwt 10meter walking test 10mwt timed 25 foot walk test t25fwt five times sit stand test 5tsts six spot step test ssst hand grip measured exercise programs feasibility acceptability exercise programs assessed eightweek periodresults hbnft significantly improved tandem walk test p0018 ssst p0026 6mwt p0037 compared hbrt significant changes differences observed outcomes p005 hbnft well tolerated resulted adverse events whereas reports pain muscle cramps extreme fatigue among hbrt participantconclusion current pilot study provided initial support hbnft safe feasible approach improving aspects ambulation persons ms cognitive impairment pilot study provides initial proofofconcept data design implementation appropriatelypowered randomized controlled trial rct neurofunctional training vs traditional resistance exercise larger sample persons ms present cooccurring impairments mobility cognition,0.0
effect desire pregnancy decisions escalate treatment multiple sclerosis care differences ms specialists nonms specialists abstractbackgroundtherapeutic inertia ti worldwide phenomenon affects 60 90 neurologists 25 daily treatment decisions management multiple sclerosis ms patients large volume ms patients women childbearing age desire pregnancy complex variable often affecting ms care objective study determine effect desire pregnancy decisions escalate treatment management ms patientsmethods300 neurologists expertise ms 20 countries invited participate study participants presented 12 pairs simulated ms patient profiles reflective case scenarios encountered clinical practice participants asked select ideal candidate treatment escalation modest higherefficacy therapies disaggregated discrete choice experiments used estimate weight factors attributes affecting physiciansnull decisions considering treatment selection excel calculator provides estimates percentage participants escalate treatment simulated casescenario constructedresults229 763 completed study mean age sd study participants 44 10 years mean sd number ms patients seen per month neurologist 18 16 nonms specialists significantly less likely escalate treatment ms specialists across mild moderate severe patient cases differences accentuated case scenarios introduced desire pregnancy findings consistent mrilesions severity symptoms number relapses includedconclusionsdesire pregnancy differentially influences decisions escalate treatment suggesting knowledgetoaction gaps ms nonms specialists findings indicate need educational strategies overcome gaps improve clinical outcomes ms patients desire pregnancy,0.0
systematic review relapse rates pregnancy postpartum patients relapsing multiple sclerosis ther adv neurol disord 2021 nov 12 1417562864211051012 doi 101177 17562864211051012 ecollection 2021abstractintroduction pregnancy widely accepted period relapses multiple sclerosis ms decreased increased risk relapse first months postpartum systematic review evaluated relapses pregnancy postpartum according diseasemodifying therapy dmt exposure pregnancy influence dmt outcomesmethods searched medline embase identify relevant publications november 2009 2019 along references lists selected articles publications filtered assessed two independent reviewers ensure appropriate data extractionresults 469 articles identified 28 included analysis including 4739 pregnancies 5324 patients five studies comparing natalizumab fingolimod highefficacy dmts use preconception versus interferon beta glatiramer acetate dimethyl fumarate dmt suggested greater risk relapse pregnancy following withdrawal highefficacy dmts 10 studies evaluating relapses pregnancy five studies found continuing dmts early pregnancy reduced relapses compared discontinuing treatment dmt exposure preconception generally effect postpartum relapses versus dmt however natalizumab fingolimod use preconception associated postpartum relapse versus highefficacy dmt one study dmt exposure pregnancy associated fewer postpartum relapses versus dmt exposure four seven studies three found difference groupsconclusion results systematic review concerning women relapsing ms show complex often conflicting picture regarding dmt exposure relapses pregnancy although data limited variability studies evidence suggesting use natalizumab fingolimod preconception associated increased risk relapses pregnancy highlighting need effective diseasemanagement strategies especially highrisk patientspmid34876925 pmcpmc8645312 doi101177 17562864211051012,0.0
dimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation abstractobjectivedimethyl fumarate dmf reported exert protective role diverse lung diseases cognitive impairmentrelated diseases thus study aimed investigate role acute lung injury ali related cognitive impairment animal modelmethodsc57bl 6 mice divided four groups control group dmf group ali group ali + dmf group ali group ali mice model created airway injection lps 50 l 1 g l ali + dmf group dmf dissolved 008 methylcellulose treated twice day 2 days third day mice injected lps ali modeling mice preadministered methylcellulose dmf without lps injection pbs instead used control group dmf group respectively morris water maze test performed treatment 0 h 6 h lpsinduction 54 h evaluate cognitive impairment mice next brain edema blood brain barrier bbb permeability ali mice assessed brain water content evans blue extravasation fitcdextran uptake assays addition effect dmf numbers total cells neutrophils protein content balf quantified inflammatory factors balf serum brain tissues examined elisa qrtpcr western blot assays effect dmf cognitive impairmentrelated factor hif1 level lung brain tissues also examined western blotresultsdmf reduced numbers total cells neutrophils protein content balf ali mice inhibited levels il6 tnf il1 balf serum brain tissues ali mice protein expressions pnfb nfb pikb ikb also suppressed dmf ali mice morris water maze test showed dmf alleviated cognitive impairment ali mice reducing escape latency path length moreover dmf lessened bbb permeability decreasing cerebral water content evans blue extravasation fitcdextran uptake ali mice hif1 levels lung brain tissues ali mice also lessened dmfconclusionin conclusion dme ability alleviate lung injury cerebral cognitive impairment ali model mice protective effect partly associated suppression inflammation dmf,0.0
aging enhances neural activity auditory visual somatosensory cortices common cause revisited humans agerelated declines vision hearing touch coincide changes amplitude latency sensory evoked potentials agerelated differences neural activity may related common deterioration supramodal brain areas eg prefrontal cortex mediate activity sensory cortices reflect specific sensorineural impairments may differ sensory modalities distinguish two possibilities measured neuroelectric brain activity 37 young adults 1830 years 18 males 35 older adults 6088 years 20 males presented rapid randomized sequence lateralized auditory visual somatosensory stimuli within sensory domain compared amplitudes latencies sensoryevoked responses source activity functional connectivity via phaselocking value groups found older adults9 early sensoryevoked responses greater amplitude young adults three modalities coincided enhanced source activity auditory visual somatosensory cortices older adults also showed stronger neural synchrony young adults superior prefrontal sensory cortices older adults degree phase synchrony positively correlated magnitude source activity sensory areas critically older adults showed enhanced neural activity one sensory domain also showed enhanced activity modalities together findings support common cause hypothesis aging highlight role prefrontal regions exerting topdown control sensory corticessignificance statementa prominent theory aging posits agerelated declines sensory processing across domains related single common neurobiological mechanism however neural evidence supporting common cause hypothesis remained elusive study revealed robust agerelated changes three sensory domains across range neural metrics importantly older adults showed increased neural activity within one sensory domain also showed enhanced neural activity two sensory modalities relation among activity sensory cortices observed young adults agerelated increases neural activity sensory cortices coincided enhanced neural synchrony prefrontal cortex sensory cortices underlining importance prefrontal cortex regulating sensory processing,0.0
remyelination prospects regenerative therapies multiple sclerosis emerg top life sci 2021 aug 20etls20210164 doi 101042 etls20210164 online ahead printabstractmultiple sclerosis ms involves immune system attacking myelin sheaths surrounding axons major cause disability workingage adults various approved therapies now provide reasonably good control ms neuroinflammation none pronounced impact neurodegeneration associated disease one prominent approach fulfilling unmet need neuroprotective therapies search agents promote remyelination namely generation new oligodendrocytes can form replacement myelin sheaths around denuded axons article discuss emerging targets remyelinating therapies mainly pursued recently formed small companies translating academic findingspmid34415022 doi101042 etls20210164,1.0
genomewide identification analysis splicing qtls multiple sclerosis rnaseq data front genet 2021 nov 12 12769804 doi 103389 fgene2021769804 ecollection 2021abstractmultiple sclerosis ms autoimmune disease characterized inflammatory demyelinating lesions central nervous system recently dysregulation alternative splicing brain found significantly influence progression ms moreover previous studies demonstrate many msrelated variants genome act important regulation factors events contribute pathogenesis ms however far genomewide research effect genomic variants events ms reported first implemented strategy obtain genomic variant genotype isoform average percentage splicedin values rnaseq data 142 individuals 51 ms patients 91 controls combing two sets data performed cissplicing quantitative trait loci sqtls analysis identify cisacting loci affected differential events ms explored characteristics cissqtls finally weighted gene coexpression network gene set enrichment analyses used investigate gene interaction pattern functions affected events ms total identified 5835 variants affecting 672 differential events cissqtls tend distributed proximity gene transcription initiation site intronic variants capable regulating events retained intron events susceptible influence genome variants functions involved protein kinase phosphorylation modification summary findings provide insight mechanism mspmid34868258 pmcpmc8633104 doi103389 fgene2021769804,1.0
regenerative effects cdpcholine dosedependent study toxic cuprizone model de remyelination pharmaceuticals basel 2021 nov 12 14 11 1156 doi 103390 ph14111156abstractinflammatory attacks demyelination central nervous system cns key factors responsible damage neurons multiple sclerosis ms remyelination natural regenerating process demyelination also provides neuroprotection often incomplete fails ms currently available therapeutics affecting immune system substance might enhance remyelination cytidinesdiphosphate choline cdpcholine precursor biomembrane component phospholipid phosphatidylcholine shown improve remyelination two animal models demyelination however doses used previous animal studies high 500 mg kg clear lower doses applied human trials might exert beneficial effect remyelination aim study confirm previous results determine potential regenerative effects lower doses cdpcholine 100 50 mg kg effects cdpcholine investigated toxic cuprizoneinduced mouse model de remyelination found even low doses cdpcholine effectively enhanced early remyelination beneficial effects myelin regeneration accompanied higher numbers oligodendrocytes conclusion cdpcholine become promising regenerative substance patients multiple sclerosis tested clinical trialpmid34832936 doi103390 ph14111156,1.0
using mixed method develop consensusbased aims contents intended learning outcomes teaching evaluation methods course epilepsy postgraduate continuing education community health nursing programs background knowledge deficits regard epilepsy reported among healthcare professionals study conducted develop consensusbased aims contents intended learning outcomes teaching evaluation methods course epilepsy postgraduate continuing education community health nursing programsmethodsa mixed method combined thorough search literature nominal group technique delphi technique survey students agreement used databases medline pubmed embase cochrane cinahl ebesco scopus google scholar google books amazon searched identify potential aims topics contents intended learning outcomes teaching evaluation methods discussions deliberations serial meetings based nominal group technique attended educators academicians n 12 neurologists n 2 practicing nurses n 5 pharmacists n 2 patients epilepsy n 2 students postgraduate continuing education programs n 7 supplement refine data collected literature qualitative data analyzed using rqda tool r delphi technique used among educators academicians n 15 neurologists n 2 practicing nurses n 5 pharmacists n 2 patients epilepsy n 3 students postgraduate continuing education programs n 8 achieve formal consensusresultsconsensus achieved 6 aims 16 intended learning outcomes 27 topics course topics 13 relevant nature epilepsy seizures 2 relevant impact epilepsy seizures different life aspects patients epilepsy 4 relevant advocating patients supporting choices 5 relevant educating patients caregivers 3 relevant assessments servicesconclusionconsensusbased aims topics contents intended learning outcomes teaching evaluation methods course epilepsy postgraduate continuing education community health nursing programs developed consensusbased courses bridge knowledge gaps improve educating community health nursing programs epilepsy studies needed determine consensusbased courses promote care patients epilepsy,0.0
retinal nerve fiber layer thickness multiple sclerosis without optic neuritis fouryear followup study oman background multiple sclerosis ms autoimmune disease attacks central nervous system optic neuritis common early manifestation retinal nerve fiber layer rnfl thickness may biomarker neuroaxonal damage ms patients sought evaluate changes rnfl thickness 4 years omani ms patients without comparison healthy control groupmethodsthis retrospective casecontrol study involved 27 ms patients 25 healthy controls optical coherence tomography performed upon first diagnosis fouryear followup differences mean rnfl thickness calculatedresultsa total 51 eyes ms group 50 eyes control group evaluated significant reduction mean rnfl thickness among ms patients followup 8121 versus 7214 m p 003 whereas significant rnfl thinning observed among ms patients without however significant reduction rnfl thickness among ms patients compared healthy controls 7679 versus 9372 m p 009 regardless presence absenceconclusionsaxonal damage seen optic nerves omani ms patients moreover significant reduction rnfl thickness among ms patients disease progressed however evidence rnfl thinning ms patients without difference lacked statistical significance evaluation rnfl thickness may represent useful biomarker monitoring disease progression ms association,0.0
myotonometric comparison sternocleidomastoideus masseter muscles multiple sclerosis patients swallowing problem healthy individuals abstractbackgrounddysphagia occurring oral pharyngeal phases swallowing ms patients may caused changes musclesnull viscoelasticity aim study compare musclesnull sternocloideomastoideus masseter viscoelasticity properties myotonometer ms patients healthy individualsmethodsthis study design crosssectional noninterventional study ten healthy individuals allocated control group eleven ms patients without swallowing problems allocated without swallowing group ten ms patients swallowing problems allocated swallowing group disability evaluated using expanded disability status scale edss swallowing problem assessed dysphagia multiple sclerosis dymus scale measure viscoelastic parameters tone stiffness elasticity sternocloideomastoideus scm masseter muscles bilaterally myotonpro used comparison groups performed using kruskalwallis h testresultsit observed difference terms viscoelastic properties masseter muscle groups p005 difference groups terms elasticity scm muscle p005 however tonus stiffness scm left side ms patients higher groups p0050 p0005 conclusionthe increment level tone stiffness scm muscle related swallowing problems patients ms due swallowing problems ms orofacial neck regionnulls musclesnull viscoelastic properties may change time may affected phases swallowing problems,0.0
recurrent ataxia dysarthria myelin oligodendrocyte glycoprotein antibodyassociated disorder bmj case rep 2021 nov 12 14 11 e245341 doi 101136 bcr2021245341abstractthe spectrum central nervous system demyelinating disorders vast heterogeneous often overlapping clinical presentations misdiagnosis might occur cases serious therapeutic repercussions however introduction several new biomarkers aquaporin4 igg myelin oligodendrocyte glycoprotein igg made distinction diseases multiple sclerosis myelin oligodendrocyte glycoprotein antibodyassociated disorder easier report case 15yearold male patient subacute multifocal neurological presentation without encephalopathy eventually diagnosed myelin oligodendrocyte glycoprotein antibodyassociated disorderpmid34772679 doi101136 bcr2021245341,1.0
multiomics study heterotardigrade echinisicus testudo suggests possibility convergent evolution abundant heatsoluble proteins tardigrada background many limnoterrestrial tardigrades can enter ametabolic state known anhydrobiosis upon desiccation animals can withstand extreme environments genomics studies molecular components anhydrobiosis beginning elucidated expansion oxidative stress response genes loss stress signaling pathways gain tardigradespecific heatsoluble protein families designated cahs sahs however date studies predominantly investigated class eutardigrada molecular mechanisms remaining class heterotardigrada still remains elusive address gap research report multiomics study heterotardigrade echiniscus testudo one desiccationtolerant species yet culturable laboratory conditionsresultsin order elucidate molecular basis anhydrobiosis e testudo employed multiomics strategy encompassing genome sequencing differential transcriptomics proteomics using ultralow input library sequencing protocol single specimen sequenced assembled 1537 mbp genome annotated using rnaseq data none previously identified tardigradespecific abundant heatsoluble genes conserved loss expansion existing pathways partly shared furthermore identified two families novel abundant heatsoluble proteins named e testudo abundant heat soluble etahs predicted contain large stretches disordered regions likewise ahs families eutardigrada etahs shows structural changes random coil alphahelix water content decreased vitro characteristics etahs proteins analogous cahs eutardigrades conservation sequence levelconclusionsour results suggest heterotardigrada partly shared distinct anhydrobiosis machinery compared eutardigrada possibly due convergent evolution within tardigrada 276 350,0.0
lymphocyteglia connection sets pace smoldering inflammation cell 2021 nov 11 184 23 56965698 doi 101016 jcell202110018abstractsuccessful therapeutic options directly targeting disability progression patients multiple sclerosis ms chronic inflammatory disorder central nervous system lacking now study published nature absinta colleagues profiles lymphocyteglia connection edge chronic active lesions continuously drives neurodegenerative pathwayspmid34767775 doi101016 jcell202110018,0.0
antibodies neurofilament light potential biomarkers multiple sclerosis bmj neurol open 2021 nov 11 3 2 e000192 doi 101136 bmjno2021000192 ecollection 2021abstractbackground objective concentration neurofilament light nfl protein cerebrospinal fluid csf blood widely considered quantitative measure neuroaxonal injury immune reactivity nfl released extracellular fluids induces specific autoantibody response investigated levels avidity antibodies nfl patients multiple sclerosis ms treated diseasemodifying therapies dmts correlation disease worsening nfl protein concentrationmethods conducted prospective longitudinal study 246 patients ms 125 dmttreated 121 untreated baseline serum levels nfl antibodies antibody avidity immune complexes determined elisa nfl protein measured using simoa platform clinical variables tested association measured parameters multivariate generalised estimating equation modelsresults multivariate analysis showed levels nfl antibodies higher progressive ms compared clinically isolated syndrome cis relapsing remitting multiple sclerosis rrms p0010 antinfl levels drop increasing disability score expanded disability status scale edss p0002 although conversely significantly elevated cis rrms recent edss increase p0012 patients receiving dmts showed decreased levels antinfl p0008 highavidity antibodies p0017 immunecomplexes compared untreated cis rrms patients ms switching natalizumab showed lower levels antinfl higher immune complexes compared healthy controls p00071 weak association observed levels nfl protein nfl antibodiesconclusions results support potential usefulness quantifying antibody response nfl potential markers progression treatment response ms need considered interpreting peripheral blood nfl levelspmid34786556 pmcpmc8587694 doi101136 bmjno2021000192,0.0
effectiveness intervention based transactional model improving coping efforts stress moderators hemodialysis patients tehran randomized controlled trial background present study conducted determine effect training coping efforts stress moderators based transactional model lazarus folkman hemodialysis patientsmethodsthis randomized controlled clinical trial 116 hemodialysis patients referred dialysis centers tehran may august 2018 patients assigned two experimental control groups using simple randomization method intervention included 6 training sessions form coping efforts moderators transactional model data collected 3 months intervention data analyzed using spss 16resultsafter 3 months training intervention significant increase intervention group mean scores coping efforts p 0001 moderators subscales emotional regulation 5118 2042 6487 1318 p 0001 dispositional coping style 4556 1945 5584 1803 social support 4961 2014 5555 1735 p 0005 conclusionthe training based transactional model successful increase social support dispositional coping style emotional regulation hemodialysis patients therefore nurses healthcare providers can use program help hemodialysis patients increase adaptation illness reduce stresstrial registrationirct registration number irct20180524039814n1 registration date 13082018 registration timing retrospectively registered last update 13082018,0.0
healthcare people multiple sclerosis germany designedthe rationale protocol mixedmethods study multiple sclerosispatientoriented care lower saxony mspov plos one 2021 nov 11 16 11 e0259855 doi 101371 journalpone0259855 ecollection 2021abstractbackground multiple sclerosis ms common autoimmune inflammatory disease central nervous system europe often causing severe physical cognitive emotional impairments currently unclear whether healthcare provisions people ms pwms line recommendations treatment based guidelines patients needs main objectives study follows investigate well pwms treated b develop needsoriented patientcentred care modelmethods mixedmethods study focuses adult pwms living lower saxony federal state germany qualitative study comprises focus groups pwms physicians people involved healthcare process well future workshop quantitative study comprises crosssectional online survey addresses patientrelevant outcomes needs previously determined literature searches focus groups will administered pwms insured statutory health insurance company involved project n7 000 survey data will linked longitudinal secondary data statutory health insurance company data german ms registry available linked single data sources will statistically analyseddiscussion comprehensively comparing current healthcare provisions needs requirements pwms strengths weaknesses overall healthcare process provision assistive devices can identified barriers facilitators health service providers impact daily life will explored qualitative analyses reliable recommendations improvements will given based study population drawn largest statutory health insurance company lower saxony quantitative analyses however inherent advantages limitations qualitative quantitative research approaches need consideredtrial registration study registered german clinical trials register drks00021741pmid34762697 doi101371 journalpone0259855,0.0
impact dietary intervention serum neurofilament light chain multiple sclerosis neurol neuroimmunol neuroinflamm 2021 nov 11 9 1 e1102 doi 101212 nxi0000000000001102 print 2022 janabstractbackground objectives adapted ketogenic diet akd caloric restriction cr suggested alternative therapeutic strategies multiple sclerosis ms information impact neuroaxonal damage lacking thus explored impact diets serum neurofilament light chain snfl levels patients relapsingremitting msmethods retrospectively evaluated prospective randomized controlled trial 60 patients ms common diet ketogenic diet fasting examined snfl levels 40 participants baseline end study 6 months using single molecule array assayresults snfl levels investigated 9 controls 14 participants cr 17 participants akd correlation analysis showed association snfl age disease duration association also found snfl multiple sclerosis functional composite akd significantly reduced snfl levels 6 months compared common diet group p 0001 discussion clinical study use consider akd may incline snfl levels independent relapse activity 3 months initiation 6 months akd complements current therapies reduced snfl levels therefore suggesting potential neuroprotective effects ms single cycle sevenday fasting affect snfl akd may addition armamentarium help clinicians support patients ms personalized manner tailored diet strategiestrial registration information clinical trial registration number nct01538355pmid34764215 doi101212 nxi0000000000001102,1.0
editorial update vascular contributions agerelated neurodegenerative diseases cognitive impairment research isnvd 2020 meeting front neurol 2021 nov 11 12797486 doi 103389 fneur2021797486 ecollection 2021no abstractpmid34858320 pmcpmc8632484 doi103389 fneur2021797486,0.0
radiological pleuroparenchymal fibroelastosislike lesion idiopathic interstitial pneumonias background pleuroparenchymal fibroelastosis ppfe characterised predominant upper lobe pleural subpleural lung parenchymal fibrosis radiological ppfelike lesion associated various types interstitial lung diseases however prevalence clinical significance radiological ppfelike lesion patients idiopathic interstitial pneumonias iips fully understood aimed determine prevalence clinical impact survival radiological ppfelike lesion patients iipsmethodsa posthoc analysis conducted using data japanese nationwide cloudbased database patients iips patients database diagnosed iips multidisciplinary discussion patients diagnosed idiopathic ppfe excluded clinical data chest computed tomography ct image 419 patients iips analysed presence radiological ppfelike lesion independently evaluated two chest radiologists blind clinical dataresultsof 419 patients iips radiological ppfelike lesions detected 101 241 patients mainly idiopathic pulmonary fibrosis ipf unclassifiable iips less idiopathic nonspecific interstitial pneumonia prognostic analyses revealed radiological ppfelike lesion significantly associated poor outcome patients iips independent age ipf diagnosis fvc survival analyses patients radiological ppfelike lesions poor survival compared without logrank p 00001 subgroup analyses demonstrated radiological ppfelike lesion significantly associated poor survival patients ipf unclassifiable iipsconclusionradiological ppfelike lesion condition exist iips mainly ipf unclassifiable iips importantly radiological ppfelike lesion noninvasive marker predict poor outcome patients iips carefully considered clinical practice,0.0
tissuebioengineering strategy modeling rare human kidney diseases vivo nat commun 2021 nov 11 12 1 6496 doi 101038 s4146702126596yabstractthe lack animal models human diseases precludes understanding disease mechanisms ability test prospective therapies vivo generation kidney organoids tuberous sclerosis complex tsc patientderivedhipscs allows us recapitulate rare kidney tumor called angiomyolipoma aml organoids derived tsc2 hipscs isogenic tsc2+ tsc2+ + hipscs share common transcriptional signature myomelanocytic cell phenotype kidney amls develop epithelial cysts replicating two major tscassociated kidney lesions driven genetic mechanisms consistently recapitulated transgenic mice transplantation multiple tsc2 renal organoids kidneys immunodeficient rats allows us model aml vivo study tumor mechanisms test efficacy rapamycinloaded nanoparticles approach rapidly ablate amls collectively experimental approaches represent innovative scalable tissuebioengineering strategy modeling rare kidney disease vivopmid34764250 doi101038 s4146702126596y,0.0
adherencia al tratamiento de la esclerosis mltiple en un programa de atencin mdica abstractadherence prescribed treatment chronic diseases occurs multiple sclerosis ms critical factor successful therapeutic response objective study evaluate association demographic variables adherence treatment population ms patients argentina retrospective cohort study ms patients received treatment diseasemodifying drugs included drug dispensing database national care medical program pami programa asistencia mdica integral conducted optimal adherence defined acquisition drug greater 80 9month followup total 648 patients included mean age 55 years iqr 4664 594 women mean adherence treatment 67 iqr 4489 optimal adherence documented 355 cases adherence injectable medications 10 lower oral drugs p 00001 use original brands associated 74 greater adherence generic drugs p 0001 conclusion adherence treatment suboptimal patagonian region use injectables generic drugs associated lower adherence therapy data important order planning sociosanitary programs aim increase therapeutic adherencekey words adherence multiple sclerosis disease modifying treatment,0.0
mapping microstructure striae human olfactory tract diffusion mri human sense smell plays important role appetite food intake detecting environmental threats social interactions memory processing however little known neural circuity supporting function olfactory tracts project olfactory bulb along base frontal cortex branching several striae meet diverse cortical regions historically using diffusion magnetic resonance imaging dmri reconstruct human olfactory tracts prevented susceptibility motion artifacts used dmri method readout segmentation long variable echotrains resolve minimize image distortions characterize human olfactory tracts vivo collected highresolution dmri data 25 healthy human participants 12 male 13 female performed probabilistic tractography using constrained spherical deconvolution individual subject level identified lateral medial intermediate striae respective cortical connections piriform cortex amygdala olfactory tubercle anterior olfactory nucleus combined individual results across subjects create normalized probabilistic atlas olfactory tracts investigated relationship olfactory perceptual scores measures white matter integrity including mean diffusivity importantly found olfactory tract mean diffusivity negatively correlated odor discrimination performance summary results provide detailed characterization connectivity human olfactory tracts demonstrate association structural integrity olfactory perceptual functionsignificance statementthis study provides first detailed vivo description cortical connectivity three olfactory tract striae human brain using diffusion magnetic resonance imaging additionally show tract microstructure correlates performance odor discrimination task suggesting link structural integrity olfactory tracts odor perception lastly generated normalized probabilistic atlas olfactory tracts may used future research study integrity health disease,0.0
comparative risk incident coronary heart disease across chronic inflammatory diseases front cardiovasc med 2021 nov 10 8757738 doi 103389 fcvm2021757738 ecollection 2021abstractbackground chronic inflammatory diseases cids considered risk enhancing factors coronary heart disease chd however sparse data exist regarding relative chd risks across cids objective determine relative differences chd risk across multiple cids psoriasis rheumatoid arthritis ra systemic lupus erythematosus sle human immunodeficiency virus hiv systemic sclerosis ssc inflammatory bowel disease ibd methods cohort included patients cids controls without cid urban medical system 2000 2019 patients cids frequencymatched noncid controls demographics hypertension diabetes chd defined myocardial infarction mi ischemic heart disease coronary revascularization based validated administrative codes multivariableadjusted cox models used determine risk incident chd mi cid relative noncid controls secondary analyses compared chd risk disease severity within cid results 17 049 patients included analysis 619 incident chd 202 mi average 44 years followup multivariableadjusted risk chd significantly higher sle hazard ratio hr 19 95 confidence interval ci 12 32 ssc hr 21 95 ci 12 39 patients sle also significantly higher risk mi hr 36 95 ci 19 68 cids categorized markers disease severity creactive protein cids except hiv cd4 t cell count used greater disease severity associated higher chd risk across cids conclusions patients sle ssc higher risk chd chd risk hiv ra psoriasis ibd may elevated greater disease severity clinicians personalize chd risk treatment based type severity cidpmid34859072 pmcpmc8631433 doi103389 fcvm2021757738,0.0
mapping connectivity fingerprints presurgical evaluation temporal lobe epilepsy background surgery may render temporal lobe epilepsy tle patients seizurefree however tle heterogenous entity surgical prognosis varies patients networkbased biomarkers shown altered tle patients hold promise classifying tle subtypes improving presurgical prognosis aim present study investigate networkbased biomarker weighted degree connectivity wdc individual level relation tle subtypes surgical prognosismethodsthirty unilateral tle patients undergoing surgical procedure anterior temporal resection 18 healthy controls included patients followedup center mean time 685 years classified seizurefree sf non seizurefree nonsf using presurgical resting state functional mri whole brain wdc values patients controls calculated divided temporal lobes three regionsofinterest rois mesial pole lateral areas known behave differently seizure onset propagation delimiting different tle profiles wdc values defined rois individual patient compared healthy groupresultsafter surgery 14 tle patients remained sf group patients higher wdc controls temporal pole p 005 well mesial regions p 0002 toberesected temporal lobe comparing sf nonsf patients stepwise binary logistic regression model including rois showed increased wdc temporal pole p 005 mesial area p 005 toberesected temporal lobe associated seizure freedom longterm surgeryconclusionsthis study provides networkbased presurgical biomarker pave way towards personalized prediction patients tle undergoing anterior temporal resections increased wdc rest signature epileptogenic area help identifying patients benefit surgery,0.0
year fear covid19 multiple sclerosis patients examination depression sleep quality quality life pandemic abstractbackgroundthe covid19 outbreak caused great fear affected many aspects life even healthy individuals become threatening people multiple sclerosis pwms aimthe aim present study evaluate depression sleep quality life one year covid19 pandemic pwms association fear covid19 parametersmethodsa total 89 pwms 262 healthy controls included descriptive crosssectional study study compared data collected pandemic data collected online approximately one year onset pandemic fear covid19 scale fcv19s worry anxiety questionnaire waq beck depression inventory bdi pittsburgh sleep quality index psqi ms quality life scale msqol54 used data collection toolsresultsthe mean age patients 4108 102 years 62 female half 506 patients working mean edss mean duration diagnosis found 133 16 773 61 respectively mean age control group 3808 114 515 female groups social pwms 798 vs hc 893 psychological pwms 618 vs hc 519 fields found affected covid19 pandemic patients 19 reported frequency exacerbations increased pandemic patient group fear coronavirus p0808 sleep quality p0906 found different control group however anxiety p0001 depression p0001 levels determined significantly higher compared prepandemic period sleep quality patients seen impaired pandemic p005 however depression scores seen change p005 although improvements energy vitality p0001 sexual function p0002 scale scores compared prepandemic period deterioration many subdimensions quality life detected multiple regression analysis demonstrated anxiety depression sleep problems predictors physical health p0001 mental health p0001 subdimensions fear coronavirus determined significant effect quality life p005 conclusionit determined pwms psychosocially affected covid19 pandemic significant deterioration sleep quality end year spent pandemic addition deterioration depression scores although statistically significant considering fact many subdimensions quality life especially associated mental health impaired can said providing psychosocial support patients important necessity,0.0
medical management heavily exposed victims experience tokaimura criticality accident j radiol prot 2021 sep 15 doi 101088 13616498 ac270d online ahead printabstracta criticality accident occurred uranium conversion plant tokaimura ibaraki prefecture japan september 30 1999 uranyl nitrate overloaded critical mass level uncontrolled fission reaction occurred procedure carried according jco manual although officially approved manual three workers heavily exposed neutrons rays produced nuclear fission subsequently developed acute radiation syndrome ars average doses whole body three workers approximately 25 9 3 gyeq biologically equivalent dose exposure respectively dose distribution analysis later revealed extreme heterogeneity doses 2 workers triaged according predicted clinical needs two workers developed severe bone marrow failure received hematopoietic stem cell transplantation one peripheral stem cell transplantation hla compatible sister umbilical cord blood transplantation graft initially successful workers autologous hematopoietic recovery observed donor recipient mixed chimerism one despite medical efforts available including hematopoietic stem cell transplantation investigational drugs skin graft two workers died multiple organ involvement failure 83 211 days accident respectively clinically well pathologically direct cause death deemed intractable gi bleeding one thoracoabdominal compartment syndrome due dermal fibrosis sclerosis third worker also developed bone marrow suppression treated granulocyte colonystimulating factor gcsf recovered without major complications now periodical medical followup experiences suggest treatment bone marrow limiting factor saving life ars victims severely exposed successful treatment organs lungs skin gastrointestinal tract also essential furthermore wholebody dose may always reflect prognosis ars victims nature accidental exposure heterogenous exposurepmid34525457 doi101088 13616498 ac270d,0.0
ancient retroviral rna element hidden mammalian genomes involvement coopted retroviral gene regulation background retroviruses utilize multiple unique rna elements control rna processing translation however unclear functional rna elements present endogenous retroviruses ervs gene cooption ervs sometimes entails conservation viral ciselements required gene expression might reveal rna regulation ervsresultshere characterized rna element found ervs consisting three specific sequence motifs called spre sprelike elements found different erv families exogenous viral sequences examined observed thousand copies sprelike elements several mammalian genomes human marmoset genomes overlapped lineagespecific ervs spre originally found human syncytin1 syncytin2 indeed several mammalian syncytin genes macsyncytin3 macaque syncytinten1 tenrec syncytincar1 carnivora contained sprelike elements reporter assay revealed enhancement gene expression spre depended reporter genes mutation spre impaired wildtype syncytin2 expression mutation affect codonoptimized syncytin2 suggesting spre activity depends coding sequenceconclusionsthese results indicate multiple independent invasions various mammalian genomes retroviruses harboring sprelike elements functional sprelike elements found several syncytin genes derived retroviruses element may facilitate expression viral genes suppressed due inefficient codon frequency repressive elements within coding sequences findings provide new insights longterm evolution rna elements molecular mechanisms gene expression retroviruses,0.0
hemispheric asymmetry reduction older adults motor cortex reflect compensation older adults tend display greater brain activation nondominant hemisphere even basic sensorimotor responses debated whether hemispheric asymmetry reduction older adults harold reflects compensatory mechanism across two independent fmri experiments involving adultlifespan human samples n 586 n 81 approximately half female performed right hand finger responses distinguished hypotheses using behavioural multivariate bayes mvb decoding approaches standard univariate analyses replicated harold pattern motor cortex outofscanner behavioural results demonstrated evidence compensatory relationship reaction time measures task performance older adults relate ipsilateral motor activity likewise mvb showed increased ipsilateral activity older adults carry additional information anything combining ipsilateral contralateral activity patterns reduced action decoding older adults least experiment 1 results contradict hypothesis harold compensatory instead suggest agerelated ipsilateral hyperactivation nonspecific line alternative hypotheses agerelated reductions neural efficiency differentiation interhemispheric inhibitionsignificance statementa key goal cognitive neuroscience ageing provide mechanistic explanation brainbehaviour relationships change age one interpretation common finding taskbased hemispheric activity becomes symmetrical older adults shift reflects compensatory mechanism nondominant hemisphere needing help computations normally performed dominant hemisphere contrary view behavioural brain data indicate additional activity ipsilateral motor cortex older adults reflective better task performance better neural representations finger actions,0.0
fasciculation differences als nonals patients ultrasound study background fasciculation important sign diagnosis amyotrophic lateral sclerosis als study aimed analyze difference fasciculation detected muscle ultrasonography mus als patients nonals patients symptoms resembling alsmethodseightyeight als patients fiftyfour nonals eight multifocal motor neuropathy 32 chronic inflammatory demyelinating polyneuropathy charcotmarietooth 14 cervical spondylopathy lumbar spondylopathy patients recruited mus performed 19 muscle groups cervical lumbosacral bulbar thoracic regions patient intensity fasciculation divided five grades based firing frequency number involved muscle groupsresultsthe overall detection rates 728 als 18 nonals patients fasciculation grades median iqr 2 03 als 0 00 nonals patients p 0001 fasciculations observed four regions als patients primarily distributed proximal limbs fasciculations nonals patients primarily lowgrade mostly distributed distal limbsdiscussionthe fasciculation grade higher als nonals patients distribution pattern fasciculation different als nonals patientsconclusionsthe fasciculation grade distribution pattern detected mus help distinguish als nonals patients,1.0
measuring productivity loss early relapsingremitting multiple sclerosis abstractbackgroundmultiple sclerosis one common causes neurological disability young adults major consequences autonomy capacity maintain employmentobjectivethe aim study assess impact work productivity earlystage relapsingremitting multiple sclerosis rrms methodsa multicenter noninterventional study conducted adult patients diagnosis rrms disease duration 3 years expanded disability status scale edss score 055 included absenteeism presenteeism unpaid work loss due rrms measured using valuation lost productivity volp questionnaire edss symptomscreen 5item modified fatigue impact scale hospital anxiety depression scale symbol digit modalities test multiple sclerosis work difficulties questionnaire used gather information disability patients perception symptom severity fatigue mood anxiety cognition problems workplace respectively associations volp clinical work outcomes analyzed using spearmannulls rank correlationsresultsa total 189 patients included mean age sd 361 94 years 714 female mean disease duration 12 08 years median edss score 10 iqr 0 20 one hundred thirty patients 688 working pay selfemployed fiftythree patients 408 reported absence work past 3 months average 143 absent workdays health problems resulted loss 34 actual work time past 7 days thirty patients got help 118 hours unpaid work activities past 7 days absenteeism significantly correlated anxiety depression rho0298 0291 p0001 fatigue rho0214 p0014 symptom severity rho0213 p0015 presenteeism significantly correlated fatigue rho0375 p0001 symptom severity rho0373 p0001 depression rho0263 p0008 disability rho0215 p0031 conclusionsproductivity loss even rrms population short disease duration stresses need efficient treatment control disease activity earlier stages,0.0
dssinduced inflammation colon drives proinflammatory signature brain ameliorated prophylactic treatment s100a9 inhibitor paquinimod background inflammatory bowel disease ibd established drive pathological sequelae organ systems outside intestine including central nervous system cns many patients exhibit cognitive deficits particularly disease flare connection colonic inflammation neuroinflammation remains unclear characterization neuroinflammatory phenotype brain colitis illdefinedmethodstransgenic mice expressing bioluminescent reporter active caspase1 treated 2 dextran sodium sulfate dss 7 days induce acute colitis colonic systemic neuroinflammation assessed experiments mice prophylactically treated paquinimod abr215757 inhibit s100a9 inflammatory signaling positive control peripheralinduced neuroinflammation mice injected lipopolysaccharide lps colonic systemic brain inflammatory cytokines chemokines measured cytokine bead array cba proteome profiler mouse cytokine array bioluminescence quantified brain caspase activation confirmed immunoblot immune cell infiltration cns measured flow cytometry light sheet microscopy used monitor changes resident microglia localization intact brains dss lpsinduced neuroinflammation rna sequencing performed identify transcriptomic changes occurring cns dsstreated mice expression inflammatory biomarkers quantified brain serum qrtpcr elisa wbresultsdsstreated mice exhibited clinical hallmarks colitis including weight loss colonic shortening inflammation colon also detected significant increase inflammatory cytokines serum brain well caspase microglia activation brain mice ongoing colitis rna sequencing brains isolated dsstreated mice revealed differential expression genes involved regulation inflammatory responses inflammatory phenotype similar signature detected lpstreated mice albeit less robust transient inflammatory gene expression returned baseline following cessation dss pharmacological inhibition s100a9 one transcripts identified rna sequencing attenuated colitis severity systemic neuroinflammationconclusionsour findings suggest local inflammation colon drives systemic inflammation neuroinflammation can ameliorated inhibition s100 alarmin s100a9,0.0
b cells cns postmortem associated worse outcome cell types multiple sclerosis neurol neuroimmunol neuroinflamm 2021 nov 10 9 1 e1108 doi 101212 nxi0000000000001108 print 2022 janabstractbackground objectives define clinical pathologic correlations compartmentalized perivascular b cells postmortem progressive multiple sclerosis ms brainsmethods brain slices acquired 11 people secondary progressive sp ms 5 people primary progressive pp ms 4 controls brain slices immunostained b lymphocytes cd20 t lymphocytes cd3 cytotoxic t lymphocytes cd8 neuronal neurofilaments nf200 myelin smi94 macrophages microglia cd68 iba1 astrocytes glial fibrillary acidic protein gfap mitochondria voltagedependent anion channel cytochrome c oxidase subunit 4 differences cd20 immunostaining intensity disease groups associations cd20 immunostaining intensity clinical variables immunostaining intensities explored linear mixed regression models cox regression models appropriateresults cd20 immunostaining intensity higher ppms coeff 0410 95 confidence interval ci 0046 0774 p 0027 spms coeff 0302 95 ci 0020 0585 p 0036 compared controls cd20 immunostaining intensity higher cerebellar spinal cord pyramidal onset coeff 0274 95 ci 0039 0510 p 0022 compared optic neuritis sensory onset higher cd20 immunostaining intensity associated younger age onset hazard ratio hr 1033 95 ci 1013 1053 p 0001 sp conversion hr 1056 95 ci 1022 1091 p 0001 wheelchair dependence hr 1472 95 ci 1108 1954 p 0008 death hr 1684 95 ci 1238 2291 p 0001 higher immunostaining intensity cd20 associated higher immunostaining intensity cd3 coeff 0114 95 ci 0005 0224 p 0040 cd8 coeff 0275 95 ci 0200 0350 p 0001 cd68 coeff 0084 95 ci 0023 0144 p 0006 gfap coeff 0002 95 ci 0001 0004 p 0030 damaged mitochondria coeff 3902 95 ci 0891 6914 p 0011 discussion perivascular b cells associated worse clinical outcomes cnscompartmentalized inflammation findings support concept targeting compartmentalized bcell inflammation progressive mspmid34759021 doi101212 nxi0000000000001108,1.0
covid19 outcomes persons multiple sclerosis treated rituximab abstractbackgroundoutcomes covid19 pwms persons multiple sclerosis immunosuppressive therapies particularly bcell depletors can unpredictable concern postponing avoiding use rituximab rtx covid19 pandemic report course outcomes covid19 pwms receiving rtxmethodspwms receiving rtx contracted covid19 closely monitored teleconsultation evaluated hospital visits requiring hospitalization oxygen therapy admission icu expiring due covid19 considered severe disease without desaturation manageable home considered mild disease disease course outcomes notedresultstwelve 62 194 pwms rtx therapy developed covid19 four age 3549 years mean 435 severe covid three secondary progressive ms spms one pwms expired two prolonged fever lasting 1 month one demonstrated features sarscov2 reactivation interval last rtx infusion average dose 750mg covid19 onset ranged 14 mean 37 months eight pwms mild covid19 age 2654 years mean 377 six rrms two spms rtx dose lower average dose 625 mg infusion covid19 onset duration longer ranging 420 mean 95 months four patients two mild severe covid19 groups neurological deterioration none true relapsesconclusionrtx treated pwms may unpredictable disease outcomes contract covid19 may risk severe disease persistent infection series higher age spms shorter interval rtx infusion covid19 onset higher dose rtx noted amongst developing severe disease rtx use cautiously covid19 pandemic unavoidable less frequent lower doses considered patients receiving rtx must counselled follow strict covid19 preventive measures,0.0
dimethyl fumarate alleviates nlrp3 inflammasome activation microglia sickness behavior lpschallenged mice front immunol 2021 nov 10 12737065 doi 103389 fimmu2021737065 ecollection 2021abstractnlrp3 inflammasome activation contributes several pathogenic conditions including lipopolysaccharide lps induced sickness behavior characterized reduced mobility depressive behaviors dimethyl fumarate dmf immunomodulatory antioxidative molecule commonly used symptomatic treatment multiple sclerosis psoriasis study investigated potential use dmf microglial nlrp3 inflammasome activation vitro vivo vitro studies lps atpstimulated n9 microglial cells used induce nlrp3 inflammasome activation dmfs effects inflammasome markers pyroptotic cell death ros formation nrf2 nfb pathways assessed vivo studies 1214 weeksold male balb c mice treated lps dmf + lps ml385 + dmf + lps behavioral tests including open field forced swim test tail suspension test carried see changes lipopolysaccharideinduced sickness behavior furthermore nlrp3 caspase1 expression isolated microglia determined immunostaining demonstrated dmf ameliorated lps atpinduced nlrp3 inflammasome activation reducing il1 il18 caspase1 nlrp3 levels reactive oxygen species formation damage inhibiting pyroptotic cell death n9 murine microglia via nrf2 nfb pathways dmf also improved lpsinduced sickness behavior male mice decreased caspase1 nlrp3 levels via nrf2 activation additionally showed dmf pretreatment decreased mir146a mir155 vivo vitro results proved effectiveness dmf amelioration microglial nlrp3 inflammasome activation anticipate study will provide foundation consideration studies aiming suppress nlrp3 inflammasome activation associated many diseases better understanding underlying mechanismspmid34858398 pmcpmc8631454 doi103389 fimmu2021737065,0.0
acute posterior reversible encephalopathy syndrome pres setting interferonbeta use case presentation reduction edema 72h cessation interferonbeta therapy subclinical inflammation background posterior reversible encephalopathy syndrome pres represents transient change mental status associated vasogenic edema cortical subcortical brain structures often attributed multifactorial etiology including hypertension altered hemodynamics disruption vessel integrity patients autoimmune disease certain immune modulator therapies greater riskcase presentationa 54yearold female past medical history wellcontrolled multiple sclerosis interferonbeta since 2013 presented witnessed tonic colonic seizure also noted demonstrate left gaze deviation leftsided hemiparesis mri fluidattenuated inversion recovery sequence showed hyperintensity subcortical u fibers concentrated occipital parietal lobes frontal lobes systolic blood pressure 160 mmhg arrival patient started seizure prophylxis interferon beta discontinued patients mentation seizures hemiapresis significantly improved next 72 h tight blood pressure control notble improvement mri imaging inflammatory markers lumbar puncture csf results devoid infectious autoimmune pathologyconclusionsa middleaged female multiple sclerosis chronic ifnbeta presented emergency room witnessed tonicclonic seizure mri t2 flair imaging consistent pres notable clinical improvement decreased edema imaging improved inflammatory markers 72 h cessation ifnbeta therapy,0.0
hypoxia kynurenine pathway implications therapeutic prospects alzheimer#39 s disease oxid med cell longev 2021 nov 10 20215522981 doi 101155 2021 5522981 ecollection 2021abstractneurodegenerative diseases nds like alzheimers disease multiple sclerosis amyotrophic lateral sclerosis parkinsons disease huntingtons disease predominantly pose significant socioeconomic burden characterized progressive neural dysfunction coupled motor intellectual impairment pathogenesis nd may result contributions certain environmental molecular factors one condition hypoxia characterized reduced organ tissue exposure oxygen reduced oxygen supply often occurs pathogenesis nd aging process despite wellestablished relationship two conditions ie hypoxia nd underlying molecular events mechanisms connecting hypoxia nd remain illdefined however relatedness may stem protective deleterious effects transcription factor hypoxiainducible factor 1alpha hif1 upregulation hif1 occurs pathogenesis nds dual function hif1 acting killer factor protective factor depends prevailing local cellular condition kynurenine pathway metabolic pathway involved oxidative breakdown tryptophan essential neurotransmission immune function like hypoxia associated nd thus good understanding factors including hypoxia ie biochemical implication hif1 kynurenine pathway activation nds focusing alzheimers disease prove beneficial new therapeutic approaches disease thus aim reviewpmid34804368 pmcpmc8598363 doi101155 2021 5522981,0.0
use caralluma fimbriata appetite suppressant weight loss supplement systematic review metaanalysis clinical trials background obesity prevalence increased past decades causing pandemic influx comorbidities many factors influence weight gain obesogenic environment therefore strategies treating obesity may vary conventional dietary physical activity interventions pharamacotherapy shift unconventional strategies herbal products treating obesity investigated one plant extract caralluma fimbriata c fimbriata studies included systematically reviewed gather evidence potential effects c fimbriata appetite suppressant weight loss supplementmethodsa systematic review clinical trials reporting effects c fimbriata appetite suppression antiobesity supplement reported according prisma guidelines data obtained searching three databases pubmed web science sciverse scopus studies published 30th april 2020resultsa total 7 articles studying c fimbriata satisfied inclusion exclusion criteria sourced various countries including australia 3 cuba 1 india 2 spain 1 almost studies recruited adults overweight obese bmi 25 kg m2 n 5 exception two studies one recruited healthy adults bmi average 265 kg m2 second one utilised population children adolescents praderwillis syndrome pws parameters assessing obesity biochemical appetite factors analysed carrying metaanalysis compared placebo controlled group c fimbriata extract significantly reduced wc 159 cm 95 ci 307 010 p 0041 whr 006 95 ci 012 001 p 005 although significant effects seen bw bmi hc biochemical appetite parameters outcome c fimbriata consumption significant changes side effects individuals ingested extract reported studies common effects constipation diarrhoea nausea rashesconclusionappetite parameters showed significant changes metabolic parameters improve cfimbriata supplementation therefore unlikely recommend c fimbriata weight loss supplement appetite suppressant,0.0
cladribine alters immune cell surface molecules adhesion costimulation insights mode action multiple sclerosis cells 2021 nov 10 10 11 3116 doi 103390 cells10113116abstractcladribine clad deoxyadenosine analogue prodrug given multiple sclerosis ms two short oral treatment courses 12 months apart reconstitution adaptive immune function following selective immune cell depletion presumed mode action exploratory study investigated impact clad tablets immune cell surface molecules adhesion cams costimulation coss people ms pwms studied 18 pwms started treatment clad 10 healthy controls hcs peripheral blood mononuclear cells collected baseline every 3 months throughout 24month period analysed icam1 lfa1 cd28 hladr cd154 cd44 vla4 cd49d cd29 psgl1 pd1 regard expression b t cells t helper th cytotoxic t cells ct surface density mean fluorescence intensity mfi flow cytometry targeted analysis cam cos surface immune cells pwms revealed higher percentage icam1 b cells th ct lfa1 b cells ct hladr b cells ct cd28 ct cd154 th pwms found lower frequencies th ct cells expressing psgl1 b cells inhibitory signal pd1 whereas surface expression lfa1 ct hladr b cells denser twentyfour months first clad cycle frequencies b cells expressing cd44 cd29 cd49d lower compared baseline together decreased densities icam1 cd44 hladr rate cd154 expressing th cells dropped 12 months ct changes seen frequency density immune reconstitution oral clad associated modification promigratory inflammatory surface patterns cams coss immune cell subsets observation pertains primarily b cells key cells underlying ms pathogenesispmid34831335 doi103390 cells10113116,0.0
focal igg4related autoimmune pancreatitis distal choledochal adenocarcinoma rare case report background autoimmune pancreatitis aip rare disease manifests pancreatic involvement systemic igg4related disease igg4rd special type chronic pancreatitis caused autoimmune abnormalities main imaging manifestations igg4related aip consist diffuse localized pancreatic enlargement irregular pancreatic duct narrowing diagnosis aip challenging can present focal lesions similar radiologically bile duct cancer pancreatic cancercase presentationa 55yearold male patient admitted painless jaundice multiple radiographic findings pancreatic head mass well intrahepatic extrahepatic bile duct dilatation various imaging methods indicated pancreatic cancer however endoscopic ultrasonography guided fine needle aspiration eusfna laparoscopic pancreatic biopsy suggested igg4related aip one month magnetic resonance imaging showed lesion slightly grown combined ca199 indexes possibility malignancy high still surgical indications pathological analysis following pancreaticoduodenectomy revealed poorly differentiated adenocarcinoma distal common bile ductconclusionto date reports described pancreatic extrapancreatic malignancies aip patients association aip bile duct adenocarcinoma previously confirmed case discuss differentiation aip malignancy recent research progress correlation two diseases highlights importance carefully evaluating patients aip rule potential tumors well critical need follow treatment,0.0
downregulation epb41l4aas1 mediated brain aging neurodegenerative diseases via damaging synthesis nad+ atp background aging neurodegenerative diseases typical metabolicrelated processes metabolismrelated long noncoding rna epb41l4aas reported potentially involved development brain aging neurodegenerative diseases study sought reveal mechanisms epb41l4aas aging neurodegenerative diseasesmethodshuman hippocampal gene expression profiles downloaded genotypetissue expression database analyzed obtain agestratified differentially expressed genes weighted correlation network analysis algorithm used construct gene coexpression network differentially expressed genes obtain gene clustering modules gene ontology kyoto encyclopedia genes genomes proteinprotein interaction network correlation analysis used reveal role epb41l4aas1 mechanism verified using gene expression omnibus dataset gse5281 biological experiments construction cell lines realtime quantitative pcr western blot measurement atp nad+ levels nicotinamide riboside treatment chromatin immunoprecipitation neurons glialderived cellsresultsepb41l4aas1 downregulated aging alzheimers disease epb41l4aas1 related genes found enriched electron transport chain nad+ synthesis pathway furthermore genes highly associated neurodegenerative diseases positively correlated epb41l4aas1 addition biological experiments proved downregulation epb41l4aas1 reduce expression genes via histone h3 lysine 27 acetylation resulting decreased nad+ atp levels epb41l4aas1 overexpression nicotinamide riboside treatment restore nad+ atp levelsconclusionsdownregulation epb41l4aas1 disturbs nad+ biosynthesis also affects atp synthesis result high demand nad+ atp brain met promoting development brain aging neurodegenerative diseases however overexpression epb41l4aas1 nicotinamide riboside substrate nad+ synthesis can reduce epb41l4aas1 downregulationmediated decrease nad+ atp synthesis results provide new perspectives mechanisms underlying brain aging neurodegenerative diseases,0.0
covid19 vaccination reactogenicity persons multiple sclerosis neurol neuroimmunol neuroinflamm 2021 nov 9 9 1 e1104 doi 101212 nxi0000000000001104 print 2022 janabstractbackground objectives limited data severe acute respiratory syndrome coronavirus 2 sarscov2 vaccine reactogenicity persons multiple sclerosis pwms reactogenicity affected diseasemodifying therapies dmts objective retrospective crosssectional study generate realworld multiple sclerosisspecific vaccine safety information particularly context specific dmts provide information mitigate specific concerns vaccine hesitant pwmsmethods 3 2021 6 2021 participants iconquerms online peoplepowered research network reported sarscov2 vaccines experiences local itch pain redness swelling warmth injection site systemic fever chills fatigue headache joint pain malaise muscle ache nausea allergic reactions within 24 hours none mild moderate severe dmt use attributes multivariable models characterized associations clinical factors reactogenicityresults 719 pwms 64 reported experiencing reaction first vaccination shot 17 reported severe reaction common reactions pain injection site 54 fatigue 34 headache 28 malaise 21 younger age female prior sarscov2 infection receiving chadox1 ncov19 oxfordastrazeneca vs bnt162b2 pfizerbiontech vaccine associated experiencing reaction first vaccine dose similar relationships observed severe reaction including higher odds reactions among pwms physical impairment lower odds reactions pwms alpha4integrin blocker sphingosine1phosphate receptor modulator 442 pwms received second vaccination shot 74 reported experiencing reaction whereas 22 reported severe reaction reaction profiles second shot similar reported first shot younger pwms received mrna1273 moderna vs bnt162b2 vaccine reported higher reactogenicity second shot whereas sphingosine1phosphate receptor modulator fumarate significantly less likely report reactiondiscussion sarscov2 vaccine reactogenicity profiles associated factors convenience sample pwms appear similar reported general population pwms specific dmts less likely report vaccine reactions overall shortterm vaccine reactions experienced study population mostly selflimiting including pain injection site fatigue headache feverpmid34753828 doi101212 nxi0000000000001104,0.0
clinical correlation multiple sclerosis immunopathologic subtypes neurology 2021 sep 9101212 wnl0000000000012782 doi 101212 wnl0000000000012782 online ahead printabstractobjective compare clinical characteristics across immunopathological subtypes patients multiple sclerosismethods immunopathological subtyping performed specimens 547 patients biopsy autopsy confirmed cns demyelinationresults frequency immunopathological subtypes pattern 23 ii 56 iii 22 immunopatterns similar terms age autopsy biopsy median age 41 years range 483 years p016 proportion female 54 p071 median followup symptom onset 23 years range 038y addition overrepresented among autopsy cases 45 vs 19 biopsy cohort p0001 index attackrelated disability higher pattern iii vs pattern ii median edss 4 vs 3 p002 monophasic clinical course common patients pattern iii pattern ii 59 vs 33 vs 32 p0001 similarly patients pattern iii pathology likely progressive disease compared patients patterns ii followed 5 years 24 overall p049 differences longterm survival despite fulminant attack presentationconclusion three immunopatterns can detected active lesions although found less frequently later disease due lower number active lesions pattern iii associated fulminant initial attack either pattern ii biopsied patients appear similar longterm outcomes irrespective immunopatterns progressive disease less associated initial immunopattern suggests convergence final common pathway related chronically denuded axonpmid34504026 doi101212 wnl0000000000012782,1.0
percutaneous posterior tibial nerve stimulation ptns lower urinary tract symptoms lutss treatment patients multiple sclerosis ms systematic review metaanalysis abstractbackground lower urinary tract symptoms lutss common patients multiple sclerosis ms percutaneous posterior tibial nerve stimulation ptns minimally invasive treatment considered effective patients suffer luts symptoms previous studies endpoints treatment reported differently designed systematic review metaanalysis estimate pooled efficacy ptns based different assessment methodsmethods systematically searched pubmed scopus embase web science google scholar also searched gray literature including references included studies conference abstracts published may 2021 search strategy included mesh text words tibial nerves posterior tibial nerve posterior tibial nerves medial plantar nerves medial plantar nerve tibial nerve stimulation transcutaneous tibial nerve stimulation percutaneous tibial nerve stimulation cutaneous tibial nerve stimulation multiple sclerosis sclerosis multiple sclerosis disseminated disseminated sclerosis ms multiple sclerosis multiple sclerosis acute fulminating two independent researchers independently evaluated articlesresults found 2430 articles literature search deleting duplicates 2027 remained eight articles remained metaanalysisthe pooled smd post voiding residual pvr posttreatment pretreatment 075 95ci093 056 i20 p067 pooled smd voiding volume posttreatment pretreatment 121 95 ci094149 i20 p04 pooled smd nocturia posttreatment pretreatment 110 95 ci133 087 i2864 p0001 pooled smd leakage per day posttreatment pretreatment 069 95 ci093 045 i2843 p0001 pooled frequency responders 66 95 ci5973 i20 conclusion results systematic review metaanalysis show ptns effective treating luts patients ms,0.0
effects hmgcoa reductase inhibitors disease activity multiple sclerosis systematic review metaanalysis statins multiple sclerosis abstractobjectiveto assess whether statins 3hydroxy3methylglutaryl coenzyme reductase inhibitors exert diseasemodifying effects multiple sclerosis ms approacha systematic review metaanalysis performed including randomizedcontrolled clinical trials rcts statin use ms randomeffects model applied calculate pooled estimates odds ratios ors corresponding 95 confidence intervals cis comparing patients treated statins alone adjunct disease modifying treatment dmt nonstatintreated patientsresultswe identified 7 rcts including 789 patients relapsingremitting ms rrms received additional dmt ifn single identified rcts secondaryprogressive ms spms clinically isolated syndrome cis optic neuritis metaanalyzed rrms addon statin use associated risk clinical relapse or130 95ci 090187 edssprogression baseline neither appeared related risk new contrastenhancing t2 lesions or128 95ci 036458 risk wholebrain volume reduction mri addon statins ifn safe welltolerated spms standalone simvastatin led significantly reduced annualized rate wholebrain volume reduction cis statins associated reduced risk new t2 lesions improved visual recovery respectivelyconclusionswe detected benefit statin treatment addon ifn rrms however potential beneficial effect spms cis deserves independent confirmation evaluation within adequately powered rcts,0.0
robust stable gene selection algorithm based graph theory machine learning background nowadays observing explosion gene expression data phenotypes enables us accurately identify genes responsible certain medical condition well classify drug target like phenotype data medical domain gene expression data phenotypes also suffer underdetermined system large set features small sample size domain eg dna microarray rnaseq data gwas data etc often reported several contrasting feature subsets may yield near equally optimal results phenomenon known instability considering facts developed robust stable supervised gene selection algorithm select set robust stable genes better prediction ability gene expression datasets phenotypes stability robustness ensured class instance level perturbations respectivelyresultswe performed rigorous experimental evaluations using 10 real gene expression microarray datasets phenotypes reveal algorithm outperforms stateoftheart algorithms respect stability classification accuracy also performed biological enrichment analysis based gene ontologybiological processes gobp terms disease ontology terms biological pathwaysconclusionsit indisputable results performance evaluations proposed method indeed effective efficient supervised gene selection algorithm,0.0
mechanisms network changes cognitive impairment multiple sclerosis neurology 2021 oct 14101212 wnl0000000000012834 doi 101212 wnl0000000000012834 online ahead printabstractbackground objectives cognitive impairment multiple sclerosis ms associated functional connectivity abnormalities calls use functional connectivity measures biomarkers remains full understanding affected ms crosssectional study tested hypothesis functional network regions may susceptible diseaserelated wearandtear can observable cooccuring abnormalities mr metrics tested whether functional connectivity abnormalities cognitively impaired ms patients cooccur either 1 overlapping 2 local 3 distal changes anatomical connectivity cerebral blood flow abnormalitiesmethods multimodal 3t mri assessment brief repeatable battery neuropsychological tests performed 102 relapsingremitting ms patients 27 healthy controls ms patients classified cognitively impaired scored 15 standard deviations control mean 2 tests n55 else cognitively preserved n47 functional connectivity assessed independent component analysis dual regression restingstate fmri images cerebral blood flow maps estimated anatomical connectivity assessed anatomical connectivity mapping fractional anisotropy diffusionweighted mri changes cerebral blood flow anatomical connectivity assessed within resting state networks showed functional connectivity abnormalities cognitively impaired ms patientsresults functional connectivity significantly decreased anterior posterior default mode networks significantly increased right left frontoparietal networks cognitively impaired relative cognitively preserved ms patients tfcecorrected p005 twosided networks showing functional abnormalities showed altered cerebral blood flow anatomical connectivity locally distally overlapping locationsdiscussion provide first evidence fc abnormalities accompanied local cerebral blood flow structural connectivity abnormalities also demonstrate effects occur exactly location findings suggest possibly shared pathological mechanism altered functional connectivity brain networks mspmid34649879 doi101212 wnl0000000000012834,0.0
prevalence pediatric onset multiple sclerosis saudi arabia mult scler int 2021 nov 9 20214226141 doi 101155 2021 4226141 ecollection 2021abstractbackground prevalence multiple sclerosis ms appears increasing worldwide however data pediatric onset ms lacking particularly developing countriesobjective study aimed reporting current burden pediatric onset ms five regions saudi arabiamethods study used relevant data national saudi ms registry operational 2015 2018 data patients pediatric onset ms hospitals included registry retrospectively analyzed using age diagnosis patients 118 years old diagnosed included analysisresults registry included 287 patients pediatric onset ms mean age diagnosis 157 sd 206 742 participants females included hospitals estimated prevalence pediatric ms 273 100 000 pediatric saudi population prevalence pediatric ms remaining nonparticipant hospitals projected taking account size pediatric population kingdom per region number facilities treating managing ms corresponding regions overall projected prevalence found 1433 100 000 saudi pediatric populationconclusion best knowledge study reported latest epidemiological data pediatric onset ms saudi arabia current prevalence ms among pediatric saudi population found 273 100 000 overall projected prevalence estimated 1433 100 000 findings similar pediatric ms cohorts studies needed understand longterm prognosis response treatment disease coursepmid34796030 pmcpmc8595009 doi101155 2021 4226141,0.0
associations diseasemodifying therapies covid19 severity multiple sclerosis neurology 2021 oct 5101212 wnl0000000000012753 doi 101212 wnl0000000000012753 online ahead printabstractbackground people multiple sclerosis ms vulnerable group severe covid 19 particularly taking immunosuppressive diseasemodifying therapies dmts examined characteristics covid19 severity international sample people msmethods data 12 datasources 28 countries aggregated sources include patients 112 countries demographic age sex clinical msphenotype disability dmt untreated alemtuzumab cladribine dimethylfumarate glatiramer acetate interferon natalizumab ocrelizumab rituximab siponimod dmts covariates queried alongside covid19 severity outcomes hospitalisation icu admission requiring artificial ventilation death characteristics outcomes assessed patients suspected confirmed covid19 using multilevel mixedeffects logistic regression adjusted age sex msphenotype edssresults 657 281 suspected 1 683 619 confirmed covid19 analysed among suspected+confirmed confirmedonly covid19 209 269 hospitalised 54 72 admitted icu 41 54 required artificial ventilation 32 39 died older age progressive msphenotype higher disability associated worse covid19 outcomes compared dimethylfumarate ocrelizumab rituximab associated hospitalisation aor156 95ci101 241 aor243 95ci148402 icu admission aor230 95ci098539 aor393 95ci156989 though rituximab associated higher risk artificial ventilation aor400 95ci1541039 compared pooled dmts ocrelizumab rituximab associated hospitalisation aor175 95ci129 238 aor276 95ci187407 icu admission aor255 95ci149436 aor432 95ci227823 rituximab artificial ventilation aor615 95ci3091227 compared natalizumab ocrelizumab rituximab wereassociated hospitalisation aor186 95ci113307 aor288 95ci168492 icu admission aor213 95ci085535 aor323 95ci117891 rituximab ventilation aor552 95ci1711784 importantly associations persisted restriction confirmed covid19 cases associations observed dmts death stratification age msphenotype edss found indications dmt associations covid19 severity reflected differential dmt allocation underlying covid19 severityconclusions using largest cohort people ms covid19 available demonstrated consistent associations rituximab increased risk hospitalisation icu admission requiring artificial ventilation ocrelizumab hospitalisation icu admission despite studys crosssectional design internal external consistency results prior studies suggests rituximab ocrelizumab use may risk factor severe covid19pmid34610987 doi101212 wnl0000000000012753,0.0
covid19 severity multiple sclerosis putting data context neurol neuroimmunol neuroinflamm 2021 nov 9 9 1 e1105 doi 101212 nxi0000000000001105 print 2022 janabstractbackground objectives unclear multiple sclerosis ms affects severity covid19 aim study compare covid19related outcomes collected italian cohort patients ms outcomes expected age sexmatched italian populationmethods hospitalization intensive care unit icu admission death covid19 diagnosis 1 362 patients ms compared age sexmatched italian population retrospective observational casecohort study populationbased control observed vs expected events compared whole ms cohort different subgroups higher risk expanded disability status scale edss score 3 least 1 comorbidity lower risk edss score 3 comorbidities 2 test risk excess quantified risk ratios rrs results risk severe events twice risk age sexmatched italian population rr 212 hospitalization p 0001 rr 219 icu admission p 0001 rr 243 death p 0001 excess risk confined higherrisk group n 553 lowerrisk patients n 809 rate events close italian age sexmatched population rr 112 hospitalization rr 152 icu admission rr 119 death lowerrisk group increased hospitalization risk detected patients anticd20 rr 303 p 0005 whereas decrease detected patients interferon 0 observed vs 4 expected events p 004 discussion overall ms cohort risk severe events twice risk age sexmatched italian population excess risk mainly explained edss score comorbidities whereas residual increase hospitalization risk observed patients anticd20 therapies decrease people interferonpmid34753829 doi101212 nxi0000000000001105,0.0
serum neurofilament light association progression natalizumabtreated patients relapsingremitting multiple sclerosis neurology 2021 sep 9101212 wnl0000000000012752 doi 101212 wnl0000000000012752 online ahead printabstractobjectivethe objective study investigate potential serum neurofilament light nfl reflect predict progression mostly independent acute inflammatory disease activity patients relapsing remitting multiple sclerosis rrms treated natalizumabmethodspatients selected prospective observational cohort study initiated 2006 vu university medical center amsterdam netherlands including patients rrms treated natalizumab selection criteria included age 18 years older minimum followup 3 years natalizumab initiation clinical mri assessments performedon yearly basis serum nfl measured 5 timepoints followup including day natalizumab initiation baseline 3 months 1 year 2 years natalizumab initiation last followup visit using general linear regression models compared longitudinal dynamics nfl patients without confirmed edss progression year 1 visit last followup individuals without edss+ progression composite endpoint including edss 9 hole peg test timed 25 footwalkresultseightynine natalizumabtreated patients rrms included median followup time 52 years iqr 4367 range 30110 natalizumab initiation mean age time natalizumab initiation 369 sd 85 median disease duration 74 years iqr 38121 year 1 last followup 28 89 315 individuals showed confirmed edss progression data edss+ endpoint available 73 89 patients 35 73 479 showed confirmed edss+ progressionwe observed significant reduction nfl levels 3 months natalizumab initiation reached nadir close 50 baseline levels 1 year treatment initiation found difference longitudinal dynamics nfl progressors versus nonprogressors nfl levels baseline 1 year natalizumab initiation predict progression last followupdiscussionin cohort natalizumabtreated patients rrms nfl fails capture predict progression occurs largely independently clinical radiological signs acute focal inflammatory disease activity additional biomarkers may thus needed monitor progression patientsclassification evidencethis study provides class ii evidence serum nfl levels associated disease progression natalizumabtreated patients rrmspmid34504023 doi101212 wnl0000000000012752,0.0
quantification normalappearing white matter damage early relapseonset multiple sclerosis neurite orientation density dispersion imaging abstractbackground neurodegeneration major contributor neurological disability multiple sclerosis ms possibility fully characterize normal appearing white matter nawm damage provide missing information needed clarify mechanism beyond disability progressionobjective present study aimed characterize presence extent nawm damage correlation clinical disabilitymethods applied diffusion tensor imaging dti neurite orientation dispersion density imaging noddi cohort 27 early relapseonset ms patients disease duration 5 years compared population 26 age sexmatched healthy controls hcs patients underwent neurological examination including expanded disability status scale edss results ms patients showed lower fractional anisotropy fa values 112 main wm bundles according jhu atlas corticospinal tract corpus callosum superior middle cerebellar peduncles posterior thalamic radiation includes optic radiation cingulum external capsule mean diffusivity md increased 412 investigated wm brain areas reduced fa also displayed increase md compared hcs brain areas reduced fa increased md also displayed reduction neurite density index ndi however comparing individual voxels wm skeleton ms hcs higher number ndi significant voxels disclosed compared fa md 564 vs 112 412 significant correlations observed dti noddi metrics edssconclusions findings suggest ndi may allow better characterization understanding microstructural changes nawm since early relapsingremitting ms phases future studies including larger cohort patients different clinical phenotypes may clarify role evaluating clinical disability,0.0
clinical application mesenchymal stem cells rheumatic diseases abstractmesenchymal stem cells mscs pluripotent stem cells derived mesoderm early development characterized high selfrenewal ability multidirectional differentiation potential cells present various tissues human body can cultured vitro specific conditions mscs can differentiate osteoblasts neuronlike cells adipocytes muscle cells therefore great application value cell replacement therapy tissue repair recent years application mscs rheumatic diseases received increasing attention one hand mscs ability differentiate bone cartilage cells hand stem cells also involved immune regulation resulting alleviation inflammation antifibrotic properties promotion vascular repair thus bringing new hope treatment rheumatic diseases article reviews clinical progress msc application treatment rheumatic diseases,0.0
relationship serum neurofilament light multiple sclerosis disability progression clear mud neurology 2021 sep 9101212 wnl0000000000012755 doi 101212 wnl0000000000012755 online ahead printno abstractpmid34504029 doi101212 wnl0000000000012755,0.0
bcell depletion covid19 severity multiple sclerosis remaining challenges neurology 2021 oct 5101212 wnl0000000000012754 doi 101212 wnl0000000000012754 online ahead printno abstractpmid34610986 doi101212 wnl0000000000012754,0.0
association small dense lowdensity lipoprotein cholesterol neuroimaging markers cerebral small vessel disease middleaged elderly chinese populations background cerebral small vascular disease csvd one leading causes death aged population closely related abnormalities lowdensity lipoprotein cholesterol ldlc study aims clarify relationship small dense lowdensity lipoprotein cholesterol sdldlc subcomponent ldlc neuroimaging markers csvdmethodsin total 1211 chinese adults aged 45 years cranial magnetic resonance imaging mri recruited retrospective study january 2018 may 2021 serum lipids baseline characteristics investigated relation occurrence csvd logistic regression model performed analyze relationships ldl subtypes csvd risk pearson correlation coefficient used analyze correlation clinical characteristics csvd risk roc curves aucs created depicted predict best cutoff value ldlc subtypes csvd risk based data performed comprehensive analyses investigate risk factors csvdresultsultimately 623 eligible patients included present study 623 eligible patients 487 included csvd group 136 included group without csvd control group adjusted confounders multivariate logistic regression model ldlc3 still higher csvd patients group without csvd 95 ci 122 108138 p 005 pearson correlation showed positive correlation levels ldlc3 ldlc4 ldlc5 glucose age hypertension previous ischemic stroke csvd risk r 015 p 001 moreover best cutoff value ldlc3 predict csvd 95 mg dl 684 sensitivity 728 specificity best cutoff value ldlc4 predict csvd 55 mg dl 505 sensitivity 904 specificityconclusionthe results indicate ldlc3 independent risk factor csvd new prediction model based ldlc3 ldlc4 can help clinicians identify highrisk csvd even people normal ldlc levels levels sdldlc considered assessment management csvd,0.0
nearinfrared aie fluorescent probe myelin imaging sciatic nerve optically cleared brain tissue 3d proc natl acad sci u s 2021 nov 9 118 45 e2106143118 doi 101073 pnas2106143118abstractmyelin structure surrounds insulates neuronal axons important component central nervous system visualization myelinated fibers brain tissues can largely facilitate diagnosis myelinrelated diseases understand brain functions however widely used fluorescent probes myelin visualization vybrant fluoromyelin strong background staining lowstaining contrast low brightness drawbacks may originate selfquenching properties greatly limit applications threedimensional 3d imaging myelin tracing chemical probes fluorescence imaging myelin 3d especially optically cleared tissue highly desirable rarely reported herein developed nearinfrared aggregationinduced emission aie active probe pmml highperformance myelin imaging pmml plasma membrane targeting good photostability specifically label myelinated fibers teased sciatic nerves mouse brain tissues highsignaltobackground ratio pmml used 3d visualization myelin sheaths myelinated fibers fascicles highpenetration depth staining compatible different brain tissueclearing methods cleart cleart2 utility pmml staining demyelinating disease studies demonstrated using mouse model multiple sclerosis together work provides important tool highquality myelin visualization across scales may greatly contribute study myelinrelated diseasespmid34740969 doi101073 pnas2106143118,1.0
subjective versus objective performance people multiple sclerosis using msreactor computerised cognitive tests abstractbackground perceived cognitive impairment ms associated adverse changes employment capacity sexual function aspects daily living studies shown relationships perceived cognitive impairment objective neuropsychological functioning mood subjective cognitive performance people ms previously compared objective performance computerised cognitive batterymethods participants completed least 6monthly serial testing msreactor computerised cognitive testing platform consisting 3 reaction time tasks measure psychomotor processing speed simple reaction time attention choice reaction time working memory one back task addition collected subjective cognitive performance patient reported outcomes depression anxiety quality life strength direction relationships subjective objective performance cognitive tasks examined using kendalls rank coefficient year 1 year 2 calculated partial correlation estimates subjective performance also associated patient reported outcomesresults subjective overall performance correlated weakly working memory task tau 010 95 confidence interval ci 019 001 subjective performance also correlated weakly depression anxiety quality life subjective reaction speed correlated weakly psychomotor processing speed tau 010 ci 019 001 subjective accuracy correlated weakly attention tau 012 ci 003 021 working memory tau 015 ci 005 024 tasks respectivelyconclusion participantsnull perceived performance msreactor tests correlated weakly objective changes depression associated subjective cognitive performance reports results suggest person msnull perception cognitive performance weakly associated cognitive changes detected using msreactor,0.0
validation fatigue severity scale croatian population patients multiple sclerosis disease factor structure internal consistency correlates abstractbackgroundfatigue common symptom people multiple sclerosis ms evaluated monitored selfreport questionnaires objective study determine psychometric properties croatian version fatigue severity scale fss people msmaterial methodsthis retrospective cohort study conducted online survey december 16 2020 january 13 2021 total 179 people ms 999 control subjects completed fss selfadministered questionnaires capturing information demographic education level diseaserelated variables duration disease ms type expanded disability status scale edss multiple sclerosis impact scale29 msis29 psychometric properties examined estimating validity reliability factor structure fss scale people msresultsthe croatian version fss excellent internal consistency cronbachnulls value 93 factor analysis demonstrated unidimensional structure concurrent validity fss appeared satisfactory due significant differences people ms control subjects p05 correlations fss msis29 physical r60 psychological r50 subscale results confirmed convergent validity fss scale results also indicated best cutoff score 4 5 relatively high sensitivity specificityconclusions croatian version fss shown excellent psychometric properties people ms can used research clinical settings evaluating fatigue people ms croatia,0.0
gadolinium enhancement cranial nerves implications interstitial fluid drainage brainstem cranial nerves humans proc natl acad sci u s 2021 nov 9 118 45 e2106331118 doi 101073 pnas2106331118abstractdrainage interstitial fluid solutes brainstem well studied map one drainage pathway human brainstem took advantage focal bloodbrain barrier disruption occurring multiple sclerosis brainstem lesion coupled intravenous injection gadolinium simulates intraparenchymal injection gadolinium tracer within restricted confines small brain region using highresolution mri show possible interstitial fluid drain adjacent trigeminal oculomotor nerves keeping pathway communication extracellular spaces brainstem cranial nerve parenchymapmid34728566 doi101073 pnas2106331118,0.0
humoral tcell responses sarscov2 vaccination multiple sclerosis patients treated ocrelizumab abstractbackground covid19 epidemic raises important questions efficacy vaccines people treated ocrelizumab anticd20 therapy ocrelizumab shown reduce humoral response sarscov2 infection vaccination tcell response vaccination fully characterized sought provide data regarding b tcell mediated responses sarscov2 vaccination ocrelizumabtreated patients determine variables correlate vaccine immunogenicity hypothesized patients without humoral response sarscov2 vaccination still intact tcell responsesmethods conducted prospective observational single center cohort study patients ms treated either ocrelizumab natalizumab comparator march 2 2021 july 1 2021 eligible patients age 18 55 known prior infection vaccination sarscov2 patients prior use immunosuppressive chemotherapeutic agents treatment anticd20 therapy ocrelizumab within 12 months enrollment excluded roche elecsys antisarscov2 s immunoassay performed prior 34 weeks post vaccination evaluate antibody response sarscov2 spike igg adaptive biotechnologies tdetect covid test performed evaluate adaptive tcell immune response sarscov2 ocrtreated patients detectable antibodies data analyzed using descriptive statistics fishernulls exact test wilcoxon rank sumresults fortyeight patients enrolled study 69 treated ocrelizumab 31 treated natalizumab eighteen percent ocrelizumab 100 natalizumab patients positive antibody response ocrelizumabtreated patients correlation age sex bmi total number infusions immunoglobulin g cd19 absolute lymphocyte count antibody response trend suggesting longer interval last infusion vaccination increased likelihood producing antibodies p0062 ocrelizumab patients negative antibody responses positive tcell responsesconclusions treatment ocrelizumab substantially impaired humoral response sarcov2 vaccination impair tcell responses research needed determine tcell response sarscov2 vaccination sufficient prevent infection reduce severity covid patients produce antibodies,0.0
longterm safety efficacy subcutaneous cladribine used increased dosage patients relapsing multiple sclerosis 20year observational study j clin med 2021 nov 8 10 21 5207 doi 103390 jcm10215207abstractcladribine currently registered 10milligram tablet formulation fixed cumulative dosage 35 mg kg 2 years important investigate increased dosage may lead clinical stability preserved safety study used offlabel subcutaneous sc formulation cladribine compared outcomes expanded disability status scale edss scores disease progression 52 relapsing multiple sclerosis rms patients receiving different sc dosing regimens 20 years followup study group received induction therapy sc cladribine 18 mg kg cumulative dose consistent 35 mg kg cladribine tablets patients subsequently offered maintenance therapy repeated courses 03 mg kg sc cladribine 520year followup fortyone patients received increased cumulative dose higher induction dose 18 mg kg 11 received standard induction dose risk progression edss correlated lower cumulative dose p 005 advanced disability treatment initiation p 005 assessed edss change year 1 years 5 10 last followup maintenance treatment safe welltolerated based limited source data subcutaneous cladribine increased cumulative maintenance dosage associated disease stability favorable safety prolonged period followup 20 years rms patientspmid34768726 doi103390 jcm10215207,0.0
measuring effects nurse practitioner np led care depression anxiety levels people multiple sclerosis study protocol randomized controlled trial background canada one highest rates multiple sclerosis ms world treatments supports people ms pwms become increasingly complex requiring individualized adaptive care specialized nps provide advanced skills complex medical conditions potential enhance health functioning quality life pwms study aims determine effect nurse practitioner np depression anxiety levels pwmsmethodswe will perform parallel randomized controlled trial pwms followed general privatepractice neurologists will randomly assigned intervention group npled care usual care control group general neurologist family physician registered nurse support intervention group np will assess provide care ms patient caregiver baseline visit 3month 6month followup visits pwms control group will receive usual care provided community neurologists family physicians standard assistance provided registered nurses experienced ms care primary outcome will difference change patients anxiety depression scores measured validated hospital anxiety depression scale hads questionnaire 3 months secondary outcomes will include difference change hads 6 months modified fatigue impact scale scores msif 3 6 months eq5d scores 3 6 months caregiver healthrelated quality life ms measures careqolms 3 6 months number visits phone calls healthcare professionals recorded patient satisfaction npled care vs usual care measured validated consultant satisfaction questionnairediscussionfindings study will contribute exploring benefits advanced nursing practitioner interventions pwms followed general neurologists family physicians community setting will provide evidence benefits npled care pwms offer alternative healthcare resource management mstrial registrationclinicaltrialsgovpro00069595 retrospectively registered june 26 2020 protocol version january 2017 version 1,0.0
comparison bone articular cartilage changes osteoarthritis microcomputed tomography histological study surgically chemically induced osteoarthritic rabbit models background osteoarthritis oa multifaceted condition affects subchondral bones articular cartilage animal models widely used effective supplement simulation human oa studies investigating disease mechanisms pathophysiology study aimed evaluate temporal changes bone cartilage surgically chemically induced osteoarthritis using microcomputed tomography histologymethodsthirty rabbits underwent either anterior cruciate ligament transection aclt procedure injected intraarticularly monosodium iodoacetate mia 8 mg right knee joint subchondral bones scanned via microct articular cartilage assessed histologically 4 8 12week postinductionresultsbased bone microarchitecture parameters surgically induced group revealed bone remodelling processes indicated increase bone volume thickening trabeculae reduced trabecular separation reduced porosity hand chemically induced group showed active bone resorption processes depicted decrease bone volume thinning trabeculae increased separation trabecular increased porosity consistently week 12 histologically chemically induced group showed severe articular cartilage damage compared surgically induced groupconclusionsit can concluded aclt group subchondral bone remodelling precedes articular cartilage damage vice versa mia group findings revealed distinct pathogenic pathways induction methods providing insight tailored therapeutic strategies well disease progression treatment outcomes monitoring,0.0
emotional experience increased emotion recognition decreased multiple sclerosis sci rep 2021 nov 8 11 1 21885 doi 101038 s4159802101139zabstractemotional disorders multiple sclerosis ms frequently described difficulties recognizing facial expressions rarely experience dimension moreover interaction emotional disorders cognitive psychological disorders remains little documented aim study explore emotions ms emotion recognition emotional experience compare data cognitive psychological disease aspects twentyfive women ms ms group 27 healthy controls control group matched age sex education assessed emotion recognition florida affect battery emotional experience international affective picture system photographs participants also assessed cognitive psychological aspects compared control group ms group difficulty recognizing emotions subjective evaluations presented iaps pictures scattered globally increased emotional dimensions correlated executive functions neither correlated alexithymia depression anxiety ms characteristics conclusion ms patients present difficulties identifying emotion emotional experience appears increased disorders correlated cognition remain independent psychological disease aspects considering implications emotional disorders may seems essential take aspects account clinical practicepmid34750435 doi101038 s4159802101139z,0.0
relationship arterial stiffness index coronary heart disease severity background arterial stiffness index asi closely related coronary atherosclerosis study aims explore whether asi can predict coronary heart disease chd severitymethodsin study total 726 patients suspected chd recruited based coronary angiography results subjects assigned three groups control group without obvious coronary artery disease singlevessel disease group multivessel disease group number vessels diseased 2 time according results angiography myocardial enzyme spectrum electrocardiogram color doppler echocardiography clinical manifestations patients divided four groups control group stable angina sa group unstable angina ua group acute myocardial infarction ami group compared whether differences asi related baseline data groups receiver operating curve roc analysis conducted determine whether asi predict chd evaluate severityresultsasi positively correlated number diseased branches coronary artery value asi increased number diseased branches increased asi value sa group significantly higher compared control group furthermore asi value ua ami groups remarkably increased compared control sa groups results roc analysis indicated sensitivity specificity asi 710 854 diagnosing chd respectively asi used predicting severity chd sensitivity 721 specificity 579conclusionasi great value diagnosis coronary heart disease prediction severity,0.0
role dendritic cells interactions pathogenesis antibodyassociated autoimmune encephalitis abstractautoimmune encephalitis ae inflammatory brain disease frequently associated antibodies abs cellsurface synaptic intracellular neuronal proteins increasing evidence dendritic cells dcs implicated key modulators keeping balance immune response tolerance cns migratory features dcs brain linked initiating maintaining neuroinflammation genetic polymorphisms together triggers systemic cerebral viral infection systemic malignancies contribute dysbalance regulatory encephalitogenic dcs subsequent dysregulated t b cell reactions ae novel vivo models implantation mature dcs containing neuronal antigens help study pathogenesis perhaps understand origin ae investigations dcs human blood lymphoid tissues csf brain parenchyma patients ae necessary deepen knowledge complex interactions dcs t b cells neuroinflammation ae can support developing new therapy strategies,0.0
treatment satisfaction safety tolerability cladribine tablets patients highly active relapsing multiple sclerosis clarifyms study 6month interim analysis abstractbackground multiple sclerosis ms chronic disabling disease associated negative effects healthrelated quality life hrqol due reduced physical psychosocial functioning cladribine tablets 10 mg 35 mg kg cumulative dose 2 years approved treatment adult patients highly active relapsing multiple sclerosis rms ongoing clarifyms study nct03369665 eudract number 201700263217 aims assess effect cladribine tablets 35mg kg hrqol patients highly active rmsobjective report design clarifyms study baseline patient characteristics results preplanned interim analysis focusing treatment satisfaction safety tolerability includes data reported till 6months start treatmentmethods clarifyms study 2year openlabel singlearm prospective multicenter phase iv study eligible patients highly active rms assigned receive cladribine tablets 35mg kg 2 years treatment satisfaction assessed using treatment satisfaction questionnaire medication tsqm v14 scale range 0 100 higher values indicating higher satisfaction safety assessments including occurrence treatmentemergent adverse events teaes adverse event reported drug administration serious adverse events saes lymphocyte counts summarized descriptivelyresults total 482 patients 85 sites europe treated cladribine tablets mean patient age 374 years 338 701 women median edss 25 345 716 prior users diseasemodifying therapy dmt first 6 months start treatment reaching full dose cladribine tablets mean tsqm global satisfaction score overall population 704 standard deviation 1848 side effects score 919 1768 convenience scored 866 1357 effectiveness 658 2114 total 275 patients 571 reported least one teae 9 patients 19 sae majority observed lymphopenia cases grade 1 2 33 68 total study cohort grade 3 lymphopenia grade 4 lymphopenia reportedconclusion patients reported high treatment satisfaction tsqm cladribine tablets preplanned interim analysis 6 months serious unexpected adverse events reported instances grade 4 lymphopenia first 6 months preliminary data indicate good tolerability convenience administration cladribine tablets patients highly active rms,0.0
rituximab people multiple sclerosis cochrane database syst rev 2021 nov 8 11cd013874 doi 101002 14651858cd013874pub2abstractbackground multiple sclerosis ms common neurological cause disability young adults offlabel rituximab ms used countries surveyed international federation ms including highincome countries onlabel diseasemodifying treatments dmts available objectives assess beneficial adverse effects rituximab first choice switching adults mssearch methods searched central medline embase cinahl trial registers completed ongoing studies 31 january 2021selection criteria included randomised controlled trials rcts controlled nonrandomised studies interventions nrsis comparing rituximab placebo another dmt adults msdata collection analysis followed standard cochrane methodology used cochrane collaborations tool assessing risk bias rated certainty evidence using grade disability worsening relapse serious adverse events saes healthrelated quality life hrqol common infections cancer mortality conducted separate analyses rituximab first choice switching relapsing progressive ms comparison versus placebo another dmt rcts nrsismain results included 15 studies 5 rcts 10 nrsis 16 429 participants 13 143 relapsing ms 3286 progressive ms studies one two years long compared rituximab first choice placebo 1 rct dmts 1 nrsi rituximab switching placebo 2 rcts dmts 2 rcts 9 nrsis studies conducted worldwide originated highincome countries six swedish ms register pharmaceutical companies funded two studies identified 14 ongoing studies rituximab first choice relapsing ms rituximab versus placebo studies met eligibility criteria comparison rituximab versus dmts one nrsi compared rituximab interferon beta glatiramer acetate dimethyl fumarate natalizumab fingolimod active relapsing ms 24 months followup rituximab likely results large reduction relapses compared interferon beta glatiramer acetate hazard ratio hr 014 95 confidence interval ci 005 039 335 participants moderatecertainty evidence rituximab may reduce relapses compared dimethyl fumarate hr 029 95 ci 008 100 206 participants lowcertainty evidence natalizumab hr 024 95 ci 006 100 170 participants lowcertainty evidence may make little difference relapse compared fingolimod hr 026 95 ci 004 169 137 participants lowcertainty evidence study reported deaths 24 months study measure disability worsening saes hrqol common infections rituximab first choice progressive ms one rct compared rituximab placebo primary progressive ms 24 months followup rituximab likely results little difference number participants disability worsening compared placebo odds ratio 071 95 ci 045 111 439 participants moderatecertainty evidence rituximab may result little difference recurrence relapses 060 95 ci 018 199 439 participants lowcertainty evidence saes 125 95 ci 071 220 439 participants lowcertainty evidence common infections 114 95 ci 075 173 439 participants lowcertainty evidence cancer 050 95 ci 007 359 439 participants lowcertainty evidence mortality 025 95 ci 002 277 439 participants lowcertainty evidence study measure hrqol rituximab versus dmts studies met eligibility criteria comparison rituximab switching relapsing ms one rct compared rituximab placebo relapsing ms 12 months followup rituximab may decrease recurrence relapses compared placebo 038 95 ci 016 093 104 participants lowcertainty evidence data confirm exclude beneficial detrimental effect rituximab relative placebo saes 090 95 ci 028 292 104 participants lowcertainty evidence common infections 091 95 ci 037 224 104 participants lowcertainty evidence cancer 155 95 ci 006 3915 104 participants lowcertainty evidence mortality 155 95 ci 006 3915 104 participants lowcertainty evidence study measure disability worsening hrqol five nrsis compared rituximab dmts relapsing ms 24 months followup data confirm exclude beneficial detrimental effect rituximab relative interferon beta glatiramer acetate disability worsening hr 086 95 ci 052 142 1 nrsi 853 participants lowcertainty evidence rituximab likely results large reduction relapses compared interferon beta glatiramer acetate hr 018 95 ci 007 049 1 nrsi 1383 participants moderatecertainty evidence fingolimod hr 008 95 ci 002 032 1 nrsi 256 participants moderatecertainty evidence data confirm exclude beneficial detrimental effect rituximab relative natalizumab relapses hr 10 95 ci 02 50 1 nrsi 153 participants lowcertainty evidence rituximab likely increases slightly common infections compared interferon beta glatiramer acetate 171 95 ci 111 262 1 nrsi 5477 participants moderatecertainty evidence compared natalizumab 158 95 ci 108 232 2 nrsis 5001 participants moderatecertainty evidence rituximab may increase slightly common infections compared fingolimod 126 95 ci 090 177 3 nrsis 5187 participants lowcertainty evidence may make little difference compared ocrelizumab 002 95 ci 000 040 1 nrsi 472 participants lowcertainty evidence data confirm exclude beneficial detrimental effect rituximab mortality compared fingolimod 559 95 ci 022 13989 1 nrsi 136 participants lowcertainty evidence natalizumab 666 95 ci 027 16658 1 nrsi 153 participants lowcertainty evidence included studies measure saes hrqol cancerauthors conclusions preventing relapses relapsing ms rituximab first choice switching may compare favourably wide range approved dmts protective effect rituximab disability worsening uncertain limited information determine effect rituximab progressive ms evidence uncertain effect rituximab saes relatively rare people ms thus difficult study well reported studies increased risk common infections rituximab absolute risk small rituximab widely used offlabel treatment people ms however randomised evidence weak absence randomised evidence remaining uncertainties beneficial adverse effects rituximab ms might clarified making realworld data availablepmid34748215 doi101002 14651858cd013874pub2,0.0
added value cognitiontargeted exercise versus symptomtargeted exercise multiple sclerosis fatigue randomized controlled pilot trial plos one 2021 nov 8 16 11 e0258752 doi 101371 journalpone0258752 ecollection 2021abstractbackground fatigue considered one common symptoms multiple sclerosis ms lacks current standardized treatment therefore aim study examine feasibility effectiveness cognitiontargeted exercise versus symptomtargeted exercise ms fatiguemethods pilot parallelgroup randomized controlled trial sixty participants multiple sclerosis randomly assigned either cognitiontargeted exercise cte n 30 mean age 41 symptomtargeted exercise ste n 30 mean age 42 participants experimental group received eight 50minute sessions weekly cognitive behavior therapy cbt addition cte program whereas participants control group received eight 50minute sessions weekly cbt addition standardized physiotherapy program ste program feasibility assessed recruitment rate participant retention adherence safety addition clinical outcome measures including 1 modified fatigue impact scale mfis 2 work social adjustment scale wsas 3 hospital anxiety depression scale hads perceived stress scale pss outcome measures assessed baseline pretreatment following completion eight visit intervention protocol 3months followupresults recruitment rate 60 93 participants completed entire study recruited participants complied 98 required visits adverse events recorded generalized estimation equation model revealed significant difference time interaction term post follow visit clinical outcome measures p 001 conclusion addition cte cbt exhibited positive lasting influence ms fatigue outcomes compared symptomtargeted exercise ste feasibility efficacy data pilot study provide support fullscale rct cte integral component multiple sclerosis fatigue managementpmid34748549 doi101371 journalpone0258752,0.0
sex differences expression endocannabinoid system within v1m cortex pag sprague dawley rats background several chronic pain disorders migraine fibromyalgia increased prevalence female population underlying mechanisms sexbiased prevalence yet thoroughly documented related endogenous differences neuromodulators pain networks including endocannabinoid system cellular endocannabinoid system comprises endogenous lipid signals 2ag 2arachidonoylglycerol aea anandamide enzymes synthesize degrade cannabinoid receptors relative prevalence different components endocannabinoid system specific brain regions may alter responses endogenous exogenous ligandsmethodsbrain tissue nave male estrous staged female sprague dawley rats harvested v1m cortex periaqueductal gray trigeminal nerve trigeminal nucleus caudalis tissue analyzed relative levels endocannabinoid enzymes ligands receptors via mass spectrometry unlabeled quantitative proteomic analysis immunohistochemistryresultsmass spectrometry revealed significant differences 2ag aea concentrations males females well female estrous cycle stages specifically 2ag concentration lower within female pag compared male pag p 00077 female 2ag concentration within pag demonstrate estrous stage dependence immunohistochemistry followed proteomics confirmed prevalence 2agendocannabinoid system enzymes female pagconclusionsour results suggest sex differences exist endocannabinoid system two cns regions relevant cortical spreading depression v1m cortex descending modulatory networks pain anxiety pag basal differences endogenous endocannabinoid mechanisms may facilitate development chronic pain conditions may also underlie sex differences response therapeutic intervention,0.0
progressive pseudorheumatoid dysplasia misdiagnosed juvenile idiopathic arthritis case report background progressive pseudorheumatoid dysplasia rare autosomal recessively inherited noninflammatory musculoskeletal disorder caused mutations occurring wnt1inducible signaling pathway protein 3 gene joint cartilage primary site involvement leading arthralgia joint stiffness contractures enlargement epiphyses metaphysis hand joints spinal abnormalities short stature early osteoarthritis osteoporosis juvenile idiopathic arthritis common chronic rheumatic disease childhood unknown etiology clinical features progressive pseudorheumatoid dysplasia resemble juvenile idiopathic arthritis patients progressive pseudorheumatoid dysplasia usually misdiagnosed juvenile idiopathic arthritiscase presentationa 13yearold yemeni female presented rheumatology clinic history joint pains bone pains bone deformity 7 years weight height third percentiles tender swelling metacarpophalangeal interphalangeal joints presented scoliosis radiographs hands revealed widening epiphyses progressive pseudorheumatoid dysplasia suspected genetic testing wnt1inducible signaling pathway protein 1 2 3 requested findings homozygous likely pathogenic variant identified wnt1inducible signaling pathway protein 3 gene confirmed diagnosisconclusionprogressive pseudorheumatoid dysplasia rare form spondyloepimetaphyseal dysplasia clinically misdiagnosed juvenile idiopathic arthritis crucial consider progressive pseudorheumatoid dysplasia especially patients standard inflammatory markers followed juvenile idiopathic arthritis improving antirheumatic intervention,0.0
headache immunological#x2f autoimmune disorders comprehensive review available epidemiological evidence insights potential underlying mechanisms abstractseveral lines evidence support role immune system headache pathogenesis particular regard migraine firstly alterations cytokine profile lymphocyte subsets reported headache patients secondly several genetic environmental pathogenic factors seem frequently shared headache immunological autoimmune diseases accordingly immunological alterations primary headaches particular migraine suggested predispose patients development immunological autoimmune diseases hand pathogenic mechanisms underlying autoimmune disorders cases seem favour onset headache therefore association headache immunological autoimmune disorders thoroughly investigated last years knowledge possible association may relevant implications clinical practice deciding diagnostic therapeutic approaches present review summarizes findings date regarding plausible relationship headache immunological autoimmune disorders starting description immunological alteration primary headaches moving onward evidence supporting potential link headache specific autoimmune immunological disease,0.0
webbased lifestyle exercise activity intervention people progressive multiple sclerosis results singlearm feasibility study abstractbackgroundpeople progressive multiple sclerosis often struggle access appropriate inclusive support regular physical activity lifestyle exercise activity package leapms intervention codesigned webbased physical activity intervention people progressive multiple sclerosis ms consists two key components 1 webbased physical activity coaching physiotherapists using selfmanagement support strategies 2 interactive webbased platform including physical activity information suite activity selection planning tool participantphysiotherapist messaging system aimed evaluate recruitment retention uptake single arm feasibility studymethodsparticipants primary secondary progressive ms expanded disability status scale score 6 8 recruited assessments included ms impact scale msis29 measures participation baseline three six months participants received intervention consisted six webbased physiotherapy led physical activity coaching sessions alongside access webbased education activity suites recruitment retention uptake data summarised predefined progression criteria used guide feasibility assessment clinical outcome data analysed descriptivelyresultsfiftyeight percent 21 36 submitting expressions interest recruited 76 completed followup prespecified progression criteria retention met recruitment meet progression criteria intervention achieved set fidelity criteria three months 12 participants 75 reported improvements routine activities intervention msis29 physical scores improved average eight points 95 ci 126 33 improvements also seen msis29 psychological scores fatigue improvements maintained six monthsconclusionsthe leapms intervention feasible associated improvements msis29 scores intervention facilitated partnership working physiotherapists people progressive ms users developed valuable skills supported selfmanagement focussing enhancing physical activity support overall wellbeing work laid foundations largescale evaluation codesigned intervention potential far reaching impact lives people progressive ms,0.0
proceedings 27th european paediatric rheumatology congress pres 2021 lightning talks autoinflammatory diseases disease outcome transition new diseases patient parent organisation initiativeso1 longterm efficacy safety canakinumab patients mevalonate kinase deficiency results randomized phase 3 cluster trialj jeyaratnam1 simon2 calvo3 t constantin4 shcherbina5 m hofer6 m gattorno7 martini8 b badermeunier9 b vastert10 j levy11 e dekker11 f de benedetti12 j frenkel11department pediatrics university medical center utrecht utrecht 2department internal medicine radboud university medical center radboudumc expertise center immunodeficiency autoinflammation reia nijmegen netherlands 3pediatric rheumatology unit hospital universitario y politcnico la fe valencia spain 42nd department pediatrics semmelweis university budapest hungary 5department immunology dmitry rogachev national medical center pediatric hematology oncology immunology moscow russian federation 6unit centre multisite romande dimmunoe rhumatologie pediatrique centre hospitalier universitaire vaudois chuv lausanne switzerland 7center autoinflammatory diseases immunodeficiencies irccs g gaslini genova 8university genoa genoa italy 9department pediatric immunology hematology rheumatology universite de paris institut des maladies genetiques imagine institute reference centre rheumatic autoimmune systemic diseases children raise necker hospital assistance publiquehopitaux de paris paris france 10department pediatric immunology university medical center utrecht netherlands 11novartis pharma ag basel switzerland 12division rheumatology ospedale pediatrico bambino ges roma italycorrespondence j jeyaratnamintroduction mevalonate kinase deficiency mkd rare monogenic autoinflammatory disease characterized fever generalized inflammation evidencebased therapy become available since canakinumab proved effective control disease activity prevent flaresobjectives study evaluated longterm efficacy safety canakinumab patients mkd open label extension period epoch 4 weeks 41 113 randomized controlled cluster trialmethods patients received open label canakinumab 150 300mg every 4 8 q4 q8 weeks study period 72 weeks stepwise dose increase maintained patients experienced flare downtitration allowed epoch 4the disease activity evaluated every 8 weeks using physician global assessment pga counting number flares measurement c reactive protein crp serum amyloid saa protein concentrations performed safety studied determination classification observed adverse events safety efficacy analyzed separately three subgroups patients receiving cumulative dose less 2700 mg 27005400mg 5400 mgresults 74 mkd patients started cluster study 66 entered epoch 4 65 completed overall 18 patients received cumulative dose 2700 mg 34 patients received 27005400 mg 14 patients received cumulative dose 5400 mgat start epoch 4 19 patients 29 receiving lowest dose regimen 150mg q8 12 18 dose sufficient control disease throughout epoch 4 another 20 patients 30 received intermediate doses 150mg q4 300mg q8 end study however highest dose 300mg q4 required 32 patients 49 end epoch 4 regimen used treat 18 patients 27 startduring 72week period 42 64 patients experienced flares 13 20 one flare compared median 12 flares per year reported baseline baseline patients mild severe disease activity according pga score low pga scores seen end study groups 90 reporting minimal disease activity none median crp concentrations consistently equal lower 10 mg l crp levels seemed slightly lower patients receiving highest cumulative dose 5400mg median saa concentrations remained slightly normal range 10mg lthe exposureadjusted rate adverse events 272 per 100 day infection frequently reported class twentyseven serious adverse events reported fourteen patients serious adverse events considered caused mkd flares eleven serious infections reported nine patients pneumonia n3 one anal abscess appendicitis bronchitis herpes virus infection influenza orchitis pyelonephritis tonsillitis conclusion canakinumab proved effective control disease activity prevent flares mkd 72week study period individual dose adjustments may required maintain therapeutic effect canakinumab new unexpected safety concerns reported,0.0
cd47 antibody blockade suppresses microgliadependent phagocytosis monocyte transition macrophages impairing recovery eae jci insight 2021 sep 30e148719 doi 101172 jciinsight148719 online ahead printabstractexperimental autoimmune encephalomyelitis eae wellcharacterized animal model multiple sclerosis early phase eae infiltrating monocyte monocytederived macrophages activated resident microglia contribute t cell recruitment especially cd4+ t cells cns resulting neuronal demyelination however later stages promote remyelination recovery removal myelin debris phagocytosis sirp cd47 abundantly expressed cns deletion either molecule protective myelin oligodendrocyte glycoprotein mog induced eae due failed effector t cell expansion trafficking report treatment function blocking cd47 antibody ab miap410 significantly reduced infiltration pathogenic immune cells impaired recovery paresis underlying mechanism blocking emergence cd11chigh mhciihigh microglia peak disease expressed receptors phagocytosis scavenging lipid catabolism mediated clearance myelin debris transition monocytes macrophages cns recovery phase eae miap410 ab treated mice worsening paresis sustained inflammation limited remyelination compared control ab treated mice summary ab blockade cd47 impaired resolution cns inflammation thus worsening eaepmid34591795 doi101172 jciinsight148719,1.0
womens experiences accessing individualized disability supports gender inequality australias national disability insurance scheme background care services industrialized nations increasingly moving towards individualized funding models aim increase individuals flexibility choice control services supports recent research suggests schemes potential exacerbate inequalities however none explored gendered dimensions inequality australian national disability insurance scheme ndis major individualized funding reform female participation rate 37 despite women girls making half disability populationmethodsthe objective study explore possible gendered barriers applying receiving adequate support ndis suggest directions future research report semistructured interviews 30 women disability explore experiences ndis perspectives challenges associated woman seeking disability support australia analyse results using thematic analysisresultsmost women sample reported differences experiences men women seeking disability support australia commonly reported gendered barriers women able access right supports disability involve confidence negotiation selfadvocacy b gendered discrimination diagnosis medical system implications disability support access c support recognition caring rolesconclusionsthese results suggest women receiving equitable treatment regard ndis research policy reform needed ensure women disability disadvantaged result move toward individualized funding models,0.0
european evidencebased recommendations clinical assessment upper limb neurorehabilitation caulin data synthesis systematic reviews clinical practice guidelines expert consensus background technologysupported rehabilitation can help alleviate increasing need costeffective rehabilitation neurological conditions use clinical practice remains limited agreement core set reliable valid accessible outcome measures assess rehabilitation outcomes needed generate strong evidence effectiveness rehabilitation approaches including technologies paper collates synthesizes core set multiple sources combining existing evidence clinical practice guidelines expert consensus european recommendations clinical assessment upper limb neurorehabilitation caulin methodsdata systematic reviews clinical practice guidelines expert consensus delphi methodology systematically extracted synthesized using strength evidence rating criteria addition recommendations assessment procedures three sets defined core set strong evidence validity reliability responsiveness clinical utility recommended least two sources extended set strong evidence recommended least two sources supplementary set evidence recommended least one sourcesresultsin total 12 measures primary focus stroke included encompassing body function activity level international classification functioning health core set recommended clinical practice research fuglmeyer assessment upper extremity fmaue action research arm test arat extended set recommended clinical practice clinical research kinematic measures box block test bbt chedoke arm hand activity inventory cahai wolf motor function test wmft nine hole peg test nhpt abilhand supplementary set recommended research specific occasions motricity index mi chedokemcmaster stroke assessment cmsa stroke rehabilitation assessment movement stream frenchay arm test fat motor assessment scale mas bodyworn movement sensors assessments conducted predefined regular intervals trained personnel global measures applied within 24 h hospital admission upper limb specific measures within 1 weekconclusionsthe caulin recommendations outcome measures assessment procedures provide clear simple evidencebased threelevel structure upper limb assessment neurological rehabilitation widespread adoption sustained use will improve quality clinical practice facilitate metaanalysis critical advancement technologysupported neurorehabilitation,0.0
neuropathic pain knee osteoarthritis background study aimed investigate relationship neuropathic pain knee osteoarthritis body composition anthropometric postural features physical function quality lifemethodspatients primary knee osteoarthritis 5070 years age included study divided group 1 neuropathic pain group 2 neuropathic pain according douleur neuropathique4 groups compared terms demographic clinical radiological laboratory findings anthropometric measurements body composition physical function tests osteoarthritis severity quality life posturographyresults200 patients included study 98 826 female group 1 102 745 female group 2 age higher group 1 compared group 2 61 5070 575 5070 respectively p 003 symptom duration also longer group 1 521 476 338 358 p 0002 body mass indices 319 56 301 48 p 0015 kellgrenlawrence class western ontario mcmaster osteoarthritis index short form36 scores unfavorable group 1 although fall risk similar stability fourier harmony indices impaired group 1 compared group 2 especially visual proprioceptive input blockedconclusionsalmost half patients knee osteoarthritis neuropathic pain associated longer symptom duration higher age lower education higher body mass index severe radilogical findings worse pain perception lower physical function quality life lower stability,0.0
relationship lymphopenia disease activity persons multiple sclerosis treated dimethyl fumarate abstractbackground dimethyl fumarate dmf diseasemodifying therapy dmt used treat relapsing multiple sclerosis ms precise mechanism treating ms involves nuclear factor erythroidderived 2related factordependent independent pathways lymphopenia defined according nih common terminology adverse events v50 one potential adverse effect unclear whether lymphopenia correlates disease activity existing studies yielded conflicting resultsobjective determine whether lymphopenia dmftreated persons ms pwms correlates disease activitymethods retrospective chart review 66 pwms treated dmf january 1 2013 september 30 2020results participants experienced lymphopenia older p0001 longer disease duration p0012 lower baseline absolute lymphocyte count alc p0001 breakthrough disease activity common reason dmf discontinuation 530 lymphopenia occurred 364 alcs decreasing first 12 months therapy plateauing lymphopenia associated trend towards reduced relapses p0059 significantly improved mri activity p0001 evidence disease activity neda3 p0022 disability progression p0549 persons lymphopenia significantly less likely treated another dmt dmf p0036 conclusion risk factors rates lymphopenia resembled existing data lymphopenia associated significantly improved mri activity achievement neda3 whether pwms treated another dmt dmf studies required clarify mechanism dmf lymphocyte subsets relationship disease activity characteristics predict response dmf,0.0
movementtomusic m2m study study protocol randomized controlled efficacy trial examining rhythmic teleexercise intervention people physical disabilities background people physical disabilities need exercise routines enjoyable readily available home adapted functional level eliminate common barriers exercise participation related transportation time commitment purpose movementtomusic m2m study address issues establishing remotely delivered rhythmic exercise program people physical disabilitiesmethodsthe study twoarm randomized controlled efficacy trial examining 12week remotely delivered m2m intervention em2m 108 people physical disabilities primary outcomes changes cardiorespiratory fitness muscle strength post 12week interventiondiscussionthe em2m study will enhance understanding alternative intervention design delivery mode removes common barriers exercise participation experienced people physical disabilities em2m intervention may alternative option people physical disabilities obtain regular exercise especially pandemic exercising indoor facilities may problematictrial registrationclinicaltrialsgov nct03797378 registered january 9 2019 trial name movementtomusic lakeshore examination activity disability exercise response study m2m leaders,0.0
therapeutic potential triptolide autoimmune diseases strategies reduce toxicity abstractwith increasing epidemiology autoimmune disease worldwide urgent need effective drugs low cost clinical treatment triptolide potent bioactive compound traditional chinese herb tripterygium wilfordii hook f possesses immunosuppression antiinflammatory activity potential drug treatment various autoimmune diseases clinical application still restricted due severe toxicity review pharmacodynamic effects pharmacological mechanisms triptolide autoimmune diseases summarized triptolide exerts therapeutic effect regulating function immune cells expression cytokines inflammatory signaling pathways well maintaining redox balance gut microbiota homeostasis meanwhile research progress toxicity triptolide liver kidney reproductive system heart spleen lung gastrointestinal tract systematically reviewed vivo experiments different animals clinical trials demonstrate dose time dependent toxicity triptolide different administration routes furthermore focus strategies reduce toxicity triptolide including chemical structural modification novel drug delivery systems combination pharmacotherapy review aims reveal potential therapeutic prospect limitations triptolide treating autoimmune diseases thus providing guiding suggestions study promoting clinical translation,0.0
osteopontin malaria direct effect parasite growth correlation p falciparumspecific b cells baff malaria endemic area background dysregulation b cell activation prevalent naturally acquired immunity malaria osteopontin opn protein produced various cells including b cells phosphorylated glycoprotein participates immune regulation suggested involved immune response malaria studied longitudinal concentrations opn infants mothers living uganda opn concentrations correlated b cell subsets specific p falciparum b cell activating factor baff also investigated direct effect opn p falciparum vitroresultsthe opn concentration higher infants compared mothers opn concentration infants decreased birth 9 months opn concentration infants 9 months independent opn concentrations corresponding mothers opn concentrations infants inversely correlated total atypical memory b cells mbcs well p falciparumspecific atypical mbcs positive correlation opn baff concentrations mothers infants opn added p falciparum cultured vitro parasitemia unaffected regardless opn concentrationconclusionsthe concentrations opn infants higher independent opn concentrations corresponding mothers vitro opn direct effect p falciparum growth correlation analysis results suggest opn role b cell immune response acquisition natural immunity malaria,0.0
virtual realitybased therapy improves fatigue impact quality life patients multiple sclerosis systematic review metaanalysis sensors basel 2021 nov 6 21 21 7389 doi 103390 s21217389abstractpatients multiple sclerosis pwms high level fatigue reduced quality life qol due impact multiple sclerosis ms virtual realitybased therapy vrbt used reduce disability pwms aim study assess effect vrbt fatigue impact ms qol pwmsmethods systematic review metaanalysis conducted bibliographic search pubmed scopus web science pedro april 2021 included randomized controlled trials rcts pwms received vrbt comparison conventional therapy ct including physiotherapy balance strength exercises stretching physical activity among others comparison simple observation order assess fatigue msimpact qol effect size calculated using cohens standardized mean difference 95 confidence interval 95 ci results twelve rcts provided data 606 pwms 4283 686 years old 70 women included methodological quality mean according pedro scale 583 083 points global findings showed vrbt effective reducing fatigue smd 033 95 ci 061 006 lowering impact ms smd 03 95 ci 055 004 increasing overall qol 05 95 ci 023 076 subgroup analysis showed following 1 vrbt better ct reducing fatigue smd 04 95 ci 07 011 well improving mental dimension qol smd 051 95 ci 002 1 2 vrbt better simple observation reducing impact ms smd 061 95 ci 097 023 increasing overall qol smd 079 95 ci 03 128 3 combined ct vrbt effective ct improving global smd 06 95 ci 013 107 physical smd 087 95 ci 03 143 mental dimensions smd 06 95 ci 008 111 qolconclusion vrbt effective reducing fatigue ms impact improving qol pwmspmid34770694 doi103390 s21217389,0.0
forensics clinical research expanding variant calling pipeline precision id mtdna whole genome panel int j mol sci 2021 nov 6 22 21 12031 doi 103390 ijms222112031abstractdespite multitude methods sample preparation sequencing data analysis mitochondrial dna mtdna demand innovation remains particularly comparison nuclear dna ndna research applied biosystems precision id mtdna whole genome panel thermo fisher scientific usa innovative library preparation kit suitable degraded samples low dna input however bioinformatic processing occurs enterprise ion torrent suite software tss yielding bam files aligned unorthodox version revised cambridge reference sequence rcrs heteroplasmy threshold level 10 present alternative customizable pipeline precisioncallerpipeline pcp processing samples correct rcrs output ion torrent sequencing precision id library kit using 18 samples 3 original samples 15 mixtures derived 1000 genomes project achieved overall improved performance metrics comparison proprietary tss optimal performance 25 heteroplasmy threshold validated findings 50 samples ongoing independent cohort stroke patients pcp finding 9831 tsss variants tss found 5792 pcps variants significant correlation variant levels variants found pipelinespmid34769461 doi103390 ijms222112031,0.0
effect body mass index brain volume cognitive function relapsingremitting multiple sclerosis combirx secondary analysis j cent nerv syst dis 2021 nov 6 1311795735211042173 doi 101177 11795735211042173 ecollection 2021abstractbackground multiple sclerosis ms autoimmune disease leading physical emotional cognitive disability high body mass index bmi may impact cognitive function brain volume ms yet paucity evidence addressing impact bmi cognitive function brain volume msobjectives purpose study examine effects bmi normal appearing brain volume cognitive function patients relapsingremitting msmethods secondary data analysis nih combirx study conducted multivariate regression mixed model analyses executed analyze effect bmi brain volume cognitive functionresults mean baseline age 768 participants 382 sd 94 years 73 female 888 caucasian mean bmi 288 kg m2 sd 67 multivariate regression mixed model analyses failed show clinical effect bmi brain volume cognitive functionconclusion bmi show effect cognitive function brain volume among ms patients although increased interest effects modifiable factors course ms effects bmi brain volume cognitive function debatable warrant researchclinicaltrialsgov nct00211887pmid34759712 pmcpmc8573693 doi101177 11795735211042173,0.0
promise micrornabased therapies alzheimers disease challenges perspectives abstractmultipathway approaches treatment complex polygenic disorders emerging alternatives classical monotarget therapies micrornas particular interest regard microrna research come long way initial discovery cumulative appreciation regulatory potential healthy diseased brain however systematic interrogation putative therapeutic toxic effects micrornas models alzheimers disease currently missing fundamental research findings yet translated clinical applications review literature summarize knowledge microrna regulation alzheimers pathophysiology critically discuss whether extent increasing insights can exploited development micrornabased therapeutics clinic,0.0
characterization mitochondrial dna quantity quality human aged alzheimers disease brain background mitochondrial dysfunction feature neurodegenerative diseases including alzheimers disease ad changes mitochondrial dna copy number mtdnacn increased mitochondrial dna mutation burden associated neurodegenerative diseases cognitive decline study aims systematically identify common brain pathologies aged human brain associated mitochondrial recalibrations disentangle relationship pathologies mtdnacn mtdna heteroplasmy aging neuronal loss cognitive functionmethodswholegenome sequencing data n 1361 human brain samples 5 different regions used quantify mtdnacn well heteroplasmic mtdna point mutations small indels brain samples assessed 10 common pathologies annual cognitive test results used assess cognitive function proximal death subset samples neuronal proportions estimated rnaseq profiles mass spectrometry used quantify mitochondrial protein content tissueresultsmtdnacn 714 lower ad relative control participants accounting 10 common neuropathologies tau significantly associated lower mtdnacn dorsolateral prefrontal cortex posterior cingulate cortex tdp43 pathology demonstrated distinct association mtdnacn changes observed cerebellum affected late pathologies neither age gender associated mtdnacn studied brain regions adjusting pathologies mitochondrial content mtdnacn independently explained variance cognitive function unaccounted pathologies implicating complex mitochondrial recalibrations cognitive decline contrast mtdna heteroplasmy levels increased 15 per year life cortical regions displayed association pathologies cognitive functionconclusionswe studied mtdna quantity quality relation mixed pathologies aging showed tau amyloid primarily associated reduced mtdnacn posterior cingulate cortex association tdp43 low mtdnacn points vulnerability region limbicpredominant agerelated tdp43 encephalopathy found low mtdnacn brain regions affected pathologies absence associations mtdna heteroplasmy burden indicates mtdna point mutations small indels unlikely involved pathogenesis lateonset neurodegenerative diseases,0.0
semantics microglia activation neuroinflammation homeostasis stress abstractmicroglia emerging critical regulators neuronal function behavior nearly every area neuroscience initial reports focused classical immune functions microglia pathological contexts however immunological concepts studies applied describe neuroimmune interactions absence disease injury infection indeed terms microglia activation neuroinflammation used ubiquitously describe changes neuroimmune function disparate contexts particularly stress research terms prompt undue comparisons pathological conditions creates barrier investigators new neuroimmunology ultimately hinders understanding stress effects microglia studies seek understand role microglia neurobiology behavior increasingly important develop standard methods study define microglial phenotype function review summarize primary research role microglia pathological physiological contexts propose framework better describe changes microglia1 phenotype function chronic stress approach will enable precise characterization microglia different contexts facilitate development microgliadirected therapeutics psychiatric neurological disease,0.0
eficacia y seguridad del rituximab en el tratamiento de la esclerosis mltiple una postura racional en el contexto colombiano summaryintroductionmultiple sclerosis neuroinflammatory chronic degenerative incurable disease associated neuronal loss increasing degrees disability cognitive control treatment causes great costs health systems society generalobjectiveto evaluate efficacy safety use rituximab management multiple sclerosismaterials methodsliterature review evaluation minihta type health technology collaborative network multiple sclerosis committee colombian association neurology global institute clinical excellenceresults27 fulltext references identified safety efficacy analysis rituximab management multiple sclerosis cost analysis epidemiological indicators pivotal studies rituximab incorporated analysisconclusionthe evidence analyzed confirms rituximab therapy effective safe management forms recurrentremittent multiple sclerosis rrms primaryprogressive multiple sclerosis ppms lower rate adverse events discontinuation withdrawal rates treatment lower diseasemodifying therapieskeywords multiple sclerosis rituximab treatment technology assessment biomedical safety treatment outcome mesh,0.0
carnosine quenches reactive carbonyl acrolein central nervous system attenuates autoimmune neuroinflammation background multiple sclerosis ms chronic autoimmune disease driven sustained inflammation central nervous system one pathological hallmarks ms extensive free radical production however subsequent generation potential pathological role detoxification different lipid peroxidationderived reactive carbonyl species neuroinflammation unclear therapeutic benefits carbonyl quenchers investigated reactive carbonyl acrolein therapeutic effect acrolein quenching carnosine neuroinflammationmethodsthe abundance localization acrolein investigated inflammatory lesions ms patients experimental autoimmune encephalomyelitis eae mice addition analysed carnosine levels acrolein quenching endogenous exogenous carnosine eae finally therapeutic effect exogenous carnosine assessed vivo eae vitro primary mouse microglia macrophages astrocytes resultsacrolein substantially increased inflammatory lesions ms patients eae mice levels dipeptide carnosine alanyllhistidine endogenous carbonyl quencher particularly reactive towards acrolein carnosineacrolein adduct carnosinepropanal twofold lower within eae spinal cord tissue oral carnosine treatment augmented spinal cord carnosine levels tenfold increased carnosineacrolein quenching reduced acroleinprotein adduct formation suppressed inflammatory activity alleviated clinical disease severity eae vivo vitro studies indicate proinflammatory microglia macrophages generate acrolein can efficiently quenched increasing carnosine availability resulting suppressed inflammatory activity properties carnosine antioxidant nitric oxide scavenging may also contribute therapeutic effectsconclusionsour results identify carbonyl particularly acrolein quenching carnosine therapeutic strategy counter inflammation macromolecular damage ms,1.0
effects melatonin sleep disturbances multiple sclerosis randomized controlled pilot study mult scler j exp transl clin 2021 nov 5 7 4 20552173211048756 doi 101177 20552173211048756 ecollection 2021 octabstractbackground sleep disturbances commonly reported people multiple sclerosis pwms however optimal management sleep disturbances uncertain objective studies sleep quality pwms scarceobjectives determine effect exogenous melatonin sleep quality sleep disturbances pwmsmethods thirty adult pwms reporting sleep difficulties recruited randomized controlled doubleblind crossover study took either melatonin placebo 2 weeks opposite following 2 weeks weeks 2 4 actigraph used capture mean total sleep time sleep efficiency patientreported outcomes pros collected weeks 0 2 4results melatonin use significantly improved mean total sleep time p 003 trend towards higher sleep efficiency p 006 pros significantly different trend melatonin use decrease mean insomnia severity index score p 007 improve pittsburgh sleep quality index sleep quality component p 007 improve neuroqolfatigue p 006 pros showed differences melatonin placebo step count measured actigraphy p 045 conclusion results provide preliminary evidence melatonin lowcost overthecounter supplement improve objective measures sleep quality pwmspmid34777854 pmcpmc8573503 doi101177 20552173211048756,0.0
severe outcomesofcovid19 among patients multiple sclerosis anticd20 therapies systematic review metaanalysis abstractbackgroundcovid19 may spread various ways ranging asymptomatic severe forms respiratory failure critical conditions death occurs particular concern patients affected multiple sclerosis especially diseasemodifying treatments studies found association anticd20 therapies especially rituximab severe covid19 however results always clear thus systematic review helpfulmethodsa systematic literature search performed independently two authors main search tools considering key inclusion criterion presence data patients ocrelizumab rituximab positive covid19 quality included studies evaluated based modified version dutch cochrane centre critical review checklist proposed moose case missing data email sent corresponding authors asking missing information excluding casereports random effects metaanalysis proportions conducted using continuity correction thei2statistic calculated measure heterogeneityresults29 articles included analysis median quality articles reached 4 5 integrated additional details provided authors articles included 5173 patients 770 148 455 88 respectively ocrelizumab rituximab pooled estimates hospitalization pneumonia intensive care unit admission 181 148 33 respectively pooled estimate death 18 overall 16 45 respectively patients ocrelizumab rituximabconclusionpatients treated rituximab seem higher risk severe covid19 outcomes compared patients treatments,0.0
nonconventional clinical uses tsh receptor antibodies case chronic autoimmune thyroiditis front endocrinol lausanne 2021 nov 5 12769084 doi 103389 fendo2021769084 ecollection 2021abstractanti tsh receptor antibodies tshrab family antibodies different activity stimulating thyroid function tsab others blocking properties tbab common finding antibodies different function might coexist patient can modulate function thyroid however labs routinely detect antibodies binding tsh receptor trab ie tshreceptor antibodies detected binding assay without definition functional property classical use tshrab assay graves disease tested diagnostic prognostic issues however can used specific settings chronic autoimmune thyroiditis cat well aim present paper highlight conditions detection tshrab can clinical relevance prevalence tshrab different 2 main form cat ie classical hashimotos thyroiditis atrophic thyroiditis tbab play major role simultaneous presence tsab tbab serum patient might clinical implication cause shift hyperthyroidism hypothyroidism vice versa evaluation trab recommended case patients thyroid associated orbitopathy associated hyperthyroidism present however relevant recommendation use trab assay patients cat secondary known agent particular treatment alemtuzumab multiple sclerosis conclusion routine use antitsh receptor antibodies either trab tsab tbab assay suggested present diagnosis follow patients affected cat however several conditions detection can clinically relevantpmid34803929 pmcpmc8602826 doi103389 fendo2021769084,0.0
changes biomarkers cigarette smoke exposure 6 days switching exclusively partially use juul system two nicotine concentrations randomized controlled confinement study adult smokers nicotine tob res 2021 jun 23ntab134 doi 101093 ntr ntab134 online ahead printabstractintroduction evidence suggests cigarette smokers switch electronic nicotine delivery systems ends reduce exposure harmful toxicants carcinogens unclear dual use associated decreases exposure toxicantsmethods parallelgroup confinement study assessed changes biomarkers exposure boes six days among healthy adult smokers randomized 1 11 study groups eight juulbrand system juul groups 4 juul flavors virginia tobacco menthol mint mango 2 nicotine concentrations 50 30 weight dual use group used preferred juul flavor 50 nicotine 50 usual brand ub cigarettes day ub cigarette group one group abstained tobacco nicotine product use abstinence group urine blood analysis assessed changes primary boe endpoints nnal 3hpma mhbma spma cohb secondary boe endpoints nnn hmpma cema 1ohp otoluidine 2na 4abp among 279 adult smokersresults juul groups median percent reductions primary boes day 6baseline 90 100 abstinence significant differences juul groups abstinence reductions juul groups substantially statistically significantly greater reductions ub cigarette group ps0025 median reductions primary boes dual use group 4355 abstinence similar results observed secondary boesconclusion study suggests use juul complete partial substitute ie dual use 50 reduction cigarette consumption combustible cigarettes can substantially reduce exposure multiple toxins associated cigarette smokingimplications study adds growing body evidence supporting utility ends products potentially reducedharm alternatives cigarettes adult smokers adult smokers switched completely cigarette smoking use juul system juul two nicotine concentrations 50 30 four flavors significantly reduced exposure multiple classes cigaretterelated toxicants additionally smokers used juul continued smoking reduced daily cigarette consumption 50 dual users also significantly reduced toxicant exposure compared cigarette smokingpmid34161586 doi101093 ntr ntab134,0.0
impact andropause multiple sclerosis front neurol 2021 nov 5 12766308 doi 103389 fneur2021766308 ecollection 2021abstractandropause results natural decrease testosterone levels occurs age contrast menopause universal wellcharacterized process associated absolute gonadal failure andropause ensues gradual decline hypothalamicpituitarygonadal axis activity well testicular function process usually develops period many years increasing evidence greater risk multiple sclerosis ms associated lower testosterone levels reported likewise epidemiological studies shown later age onset ms men relative women perhaps respond decline protective testosterone levels review will discuss role androgens development function innate adaptive immune response well neuroprotective mechanisms relevant ms testosterone effects observed different animal models epidemiological studies humans will discussed well correlation physical disability cognitive function levels finally published ongoing clinical trials exploring role androgens particularly key stages sexual maturation will reviewedpmid34803897 pmcpmc8602357 doi103389 fneur2021766308,1.0
fisetin potential flavonoid multifarious targets treating neurological disorders updated review eur j pharmacol 2021 sep 10174492 doi 101016 jejphar2021174492 online ahead printabstractneurodegenerative disorders pose significant health burden imprint debilitative impact quality life importantly aging intricately intertwined progression disorders prevalence increases rise aging population worldwide recent times fisetin emerged one potential miracle molecules address neurobehavioral cognitive abnormalities effects attributed actions several macromolecules multiple molecular mechanisms fisetin belongs class flavonoids found abundantly several fruits vegetables fisetin manifested several health benefits preclinical models neurodegenerative diseases alzheimers disease vascular dementia schizophrenia parkinsons disease amyotrophic lateral sclerosis huntingtons disease stroke traumatic brain injury tbi ageassociated changes review aimed evaluate potential mechanisms pharmacological effects fisetin treating several neurological diseases review also provides comprehensive data uptodate recent literature highlights various mechanistic pathways pertaining fisetins role treating various neurodegenerative diseasespmid34516952 doi101016 jejphar2021174492,0.0
distinct effect prenatal postnatal brain expression across 20 brain disorders anthropometric social traits systematic study spatiotemporal modularity brief bioinform 2021 jun 4bbab214 doi 101093 bib bbab214 online ahead printabstractdifferent spatiotemporal abnormalities implicated different neuropsychiatric disorders anthropometric social traits yet investigation temporal network modularity brain tissue transcriptomics lacking developed supervised network approach investigate genomewide association study gwas results spatial temporal contexts demonstrated 20 brain disorders anthropometric social traits brainspan transcriptome profiles used discover significant modules enriched trait susceptibility genes developmental stagestratified manner investigated whether developmental stages gwasimplicated genes coordinately expressed brain transcriptome identified significant network modules disorder trait different developmental stages providing systematic view network modularity specific developmental stages myriad brain disorders traits specifically observed strong pattern fetal origin psychiatric disorders traits schizophrenia scz bipolar disorder obsessivecompulsive disorder neuroticism whereas increased coexpression activities genes strongly associated neurological diseases alzheimers disease ad amyotrophic lateral sclerosis anthropometric traits college completion education subjective wellbeing postnatal brains analyses revealed enriched cell types functional features supported corroborated prior knowledge specific brain disorders clathrinmediated endocytosis ad myelin sheath multiple sclerosis regulation synaptic plasticity college completion education study provides landscape view spatiotemporal features myriad brainrelated disorders traitspmid34086851 doi101093 bib bbab214,1.0
interferons pain infections emerging roles neuroimmune neuroglial interactions front immunol 2021 nov 5 12783725 doi 103389 fimmu2021783725 ecollection 2021abstractinterferons ifns cytokines possess antiviral antiproliferative immunomodulatory actions ifn ifn two major family members typei ifns used treat diseases including hepatitis multiple sclerosis emerging evidence suggests typei ifn receptors ifnars also expressed microglia astrocytes neurons central peripheral nervous systems apart canonical transcriptional regulations ifn ifn can rapidly suppress neuronal activity synaptic transmission via nongenomic regulation leading potent analgesia ifn member typeii ifn family induces central sensitization microglia activation persistent pain discuss typei typeii ifns regulate pain infection via neuroimmune modulations special focus neuroinflammation neuroglial interactions also highlight distinct roles typei ifns peripheral central nervous system insights ifn signaling nociceptors distinct actions physiological vs pathological acute vs chronic conditions will improve treatments pain surgeries traumas infectionspmid34804074 pmcpmc8602180 doi103389 fimmu2021783725,0.0
molecular characterization gut microbiome egyptian patients remitting relapsing multiple sclerosis abstractbackgroundmultiple sclerosis common chronic demyelinating disease central nervous system representing main cause nontraumatic disabling disorders young adults etiology multiple sclerosis fully appreciated although strong evidence points genetic environmental factors role gut microbiome multiple sclerosis pathogenesis rapidly emerging area study fieldaimthe aim present study identify gut microbiome likely related multiple sclerosis well possible role susceptibility course diseasemethodsthirty egyptian patients relapsing remitting multiple sclerosis presented multiple sclerosis clinic alexandria university hospital enrolled study diagnosed according mcdonald 2017 criteriaa cross matching control group 20 healthy subjects similar age sex included stool specimens taken detection gut microbiome profile quantitative sybr green real time pcr assayresultsthe present study demonstrate rrms patients distinct gut microbiome compared healthy controls certain gut microbes showing decreased increased abundance multiple sclerosis patients compared controlsmultiple sclerosis patients significantly higher b fragilis normal control although level prevotella lactobacilli appear much less ms patients control difference statistically significant c perfringes higher multiple sclerosis patientsconclusionthe overall results study agree previous studies reporting patients multiple sclerosis egypt exhibit microbial gut dysbiosis however results individual bacteria may differ according age treatment level physcial exercise type therapy time enrollment,1.0
translation validation persian version godin leisuretime exercise questionnaire patients multiple sclerosis abstractstudy designpsychometric studyobjectivethe purpose study translate culturally adapt evaluate validity reliability persian farsi version glteq patients multiple sclerosismethodsthis study three phases including translation questionnaire persian making cultural adaptation evaluation prefinal version questionnaires comprehensibility pilot study investigation reliability validity final version translated questionnaire content validity convergent validity correlations among persian version glteq global physical activity questionnaire gpaq international physical activity questionnaire ipaq testretest reliability studiedresultsthe subjects 87 ms patients persian version demonstrated moderate good convergent validity correlation coefficient persian version gpaq r064 p0001 persian version ipaq r059 p0001 testretest reliability strong intraclass correlation icc value ranged 0908 0992 besides face validity content validity acceptableconclusionsthe persian version glteq valid reliable instrument assess physical activity patients ms questionnaire can step toward standardization physical activity measurement patients ms also research provides possibilities carry comparative study across cultures using outcome measure,0.0
silyl resveratrol derivatives potential therapeutic agents neurodegenerative neurological diseases eur j med chem 2021 jun 18 223113655 doi 101016 jejmech2021113655 online ahead printabstractnatural phenolic compounds found food demonstrated interesting preventive therapeutic effects large variety pathologies indeed resveratrol res examined clinical trials nevertheless success scarce mainly due low bioavailability study found serendipitously osilyl res derivatives exerted better neuroprotective activity resveratrol decided explore potential drugs neurodegenerative neurological diseases also designed prepared series osilyl res prodrugs improve bioavailability found ditriethylsilyl ditriisopropylsilyl res derivatives better vitro neuroprotective antiinflammatory agents res among derivatives corresponding acyl glycosyl carbamoylprodrugs 3 5triethylsilyl4 6octanoylglucopyranosyl resveratrol 26 showed best profile toxicity neuroprotective activity zebra fish embryo compound 26 also capable reducing loss motor coordination 3nitropropionic acid mice model huntingtons disease similar way res however 26 diminished proinflammatory cytokine il6 higher extent res improved latency fall rotarod test 10 respect res finally investigated 26 res potential treatments experimental autoimmune encephalomyelitis eae multiple sclerosis mice model observed therapeutic regimen 26 significantly diminished progression eae severity reduced percentage animals moderate severe clinical score whereas res showed improvementpmid34175536 doi101016 jejmech2021113655,1.0
identification viralmediated pathogenic mechanisms neurodegenerative diseases using networkbased approaches brief bioinform 2021 may 10bbab141 doi 101093 bib bbab141 online ahead printabstractduring course viral infection virushost proteinprotein interactions ppis play critical role allowing viruses replicate survive within host interspecies molecular interactions can lead viralmediated perturbations human interactome causing generation various complex diseases evidences suggest viralmediated perturbations possible pathogenic etiology several neurodegenerative diseases nds diseases characterized chronic progressive degeneration neurons current therapeutic approaches provide mild symptomatic relief therefore unmet need discovery novel therapeutic interventions paper initially review databases tools can utilized investigate viralmediated perturbations complex nds using networkbased analysis examining interaction ndrelated ppi disease networks virushost ppi network afterwards present theoreticaldriven integrative networkbased bioinformatics approach accounts pathogengenesdiseaserelated ppis aim identify viralmediated pathogenic mechanisms focusing multiple sclerosis ms disease identified seven high centrality nodes can act disease communicator nodes exert systemic effects msenriched kyoto encyclopedia genes genomes kegg pathways network addition identified 12 kegg pathways 5 reactome pathways 52 gene ontology immune system processes 80 viral proteins eight viral species might exert viralmediated pathogenic mechanisms ms finally analysis highlighted th17 differentiation pathway disease communicator node part 12 underlined kegg pathways key viralmediated pathogenic mechanism possible therapeutic target ms diseasepmid34237135 doi101093 bib bbab141,0.0
sfrp1 modulates astrocytetomicroglia crosstalk acute chronic neuroinflammation embo rep 2021 sep 27e51696 doi 1015252 embr202051696 online ahead printabstractneuroinflammation common feature many neurodegenerative diseases fosters dysfunctional neuronmicrogliaastrocyte crosstalk turn maintains microglial cells perniciously reactive state often enhances neuronal damage molecular components mediate critical communication fully explored show secreted frizzledrelated protein 1 sfrp1 multifunctional regulator celltocell communication part cellular crosstalk underlying neuroinflammation mouse models acute chronic neuroinflammation sfrp1 largely astrocytederived promotes sustains microglial activation thus chronic inflammatory state sfrp1 promotes upregulation components hypoxiainduced factordependent inflammatory pathway lower extent downstream nuclear factorkappa b thus propose sfrp1 acts astrocytetomicroglia amplifier neuroinflammation representing potential valuable therapeutic target counteracting harmful effect chronic inflammation several neurodegenerative diseasespmid34569685 doi1015252 embr202051696,0.0
corneal confocal microscopy demonstrates axonal loss different courses multiple sclerosis sci rep 2021 nov 4 11 1 21688 doi 101038 s41598021012261abstractaxonal loss main determinant disease progression multiple sclerosis ms study aimed assess utility corneal confocal microscopy ccm detecting corneal axonal loss different courses ms results confirmed two independent segmentation methods 72 subjects 144 eyes clinically isolated syndrome n 9 relapsingremitting ms n 20 secondaryprogressive ms n 22 agematched healthy controls n 21 underwent ccm assessment disability status two independent algorithms accmetrics voxeleron deepnerve used quantify corneal nerve fiber density cnfd accmetrics corneal nerve fiber length cnfl corneal nerve fractal dimension cnfrd data expressed mean standard deviation 95 confidence interval ci compared controls patients ms significantly lower cnfd 3476 557 vs 1985 675 fibers mm2 95 ci 1824 1159 p 0001 cnfl accmetrics 1975 239 vs 1240 330 mm mm2 95 ci 894 577 p 0001 deepnerve 2198 276 vs 1440 417 mm mm2 95 ci 955 56 p 0001 cnfrd accmetrics 152 002 vs 145 004 95 ci 009 005 p 0001 deepnerve 129 003 vs 119 007 95 013 007 p 0001 corneal nerve parameters comparably reduced different courses ms excellent reproducibility algorithms significant corneal axonal loss detected different courses ms including patients clinically isolated syndromepmid34737384 doi101038 s41598021012261,0.0
accuracy stroke volume measurement phasecontrast cardiovascular magnetic resonance patients aortic stenosis background phase contrast pc cardiovascular magnetic resonance cmr ascending aorta aao widely used calculate left ventricular lv stroke volume sv accuracy pc cmr may altered turbulent flow measurement sv another site suggested presence aortic stenosis data validates accuracy inaccuracy pc setting objective compare flow measurements obtained aao lv outflow tract lvot patients aortic stenosismethodsretrospective analysis patients aortic stenosis cmr echocardiography patients mitral regurgitation excluded pc aao lvot acquired derive sv lv sv endsystolic enddiastolic tracings used reference measure difference 10 volumetric method pc derived svs considered discordant metrics turbulence jet eccentricity assessed explore predictors discordant measurementsresultswe included 88 patients 41 bicuspid aortic valve lvot sv concordant volumetric method 79 90 patients vs 52 59 patients aao sv p 0015 multivariate analysis aortic stenosis flow jet angle strong predictor discordant measurement aao p 0003 mathematical correction jet angle improved concordance 59 91 concordance comparable patients bicuspid trileaflet valves 57 62 concordance respectively p 011 accuracy sv measured lvot influenced jet eccentricity aortic regurgitation quantification pc aao better correlation volumetric assessments lvot pcconclusionlvot pc sv patients aortic stenosis eccentric jet might accurate compared aao sv mathematical correction jet angle aao might another alternative improve accuracy,0.0
persistent hypercalcemia similar familial hypocalciuric hypercalcemia features case report literature review background primary hyperparathyroidism phpt familial hypocalciuric hypercalcemia fhh important differential diagnosis parathyroid hormone pth dependent hypercalcemia clinical features fhh phpt can overlap cases therefore two diseases must differentiated prevent unnecessary parathyroidectomy present case entirely matched known differential diagnoses hypercalcemiacase presentationa 19yearold girl history disease presented persistent hypercalcemia without specific musculoskeletal complaint found persistent hypercalcemia routine laboratory data 3 years ago data available childhood period dietary calcium intake normal mention history renal stone bone fracture well family history hypercalcemia biochemical features showed normal values serum creatinine high normal serum calcium range 103113 mg dl normal range 88104 nonsuppressed pth levels range 372581 pg ml normal range 1065 serum 25 oh vitamin d level first visit 161 ng ml treated vitamin d supplementation since 25 oh vitamin d levels acceptable range correction vitamin d deficiency followup period calcium creatinine clearance ratio s cccr calculated range 0009 0014 means 1 clinical laboratory data indicate fhh rather phpt genetic studies negative common genes associated fhh casr gna11 ap2s1 genes multiple endocrine neoplasia type1 men1 hand evidence autoimmunity found support autoimmune fhhlike syndrome hence case match completely diagnosis fhh phpt decided follow herconclusionwe presented patient fhh phenotype whose common genetic tests negative research needed ascertain causes leading similar manifestations,0.0
clinical efficacy safety fulldose versus halfdose corticosteroids plus leflunomide iga nephropathy background results leflunomide lef patients iga nephropathy igan inconsistentmethodsa total 149 kidney biopsyconfirmed igan patients estimated glomerular filtration rate egfr 50 ml min 173 m2 protein excretion levels 075 g d enrolled 65 subjects receiving halfdose cs plus lef lef group 84 counterpart patients accepting fulldose corticosteroid full cs group primary outcomes included complete remission cr rates incidence adverse events aes secondary outcomes overall remission rates combined event egfr reduced 30 endstage renal disease esrd hemodialysis peritoneal dialysis kidney transplantation resultsduring 18 months followup cr rates 72 64 lef full cs groups p 0299 respectively proportion patients rates lef group full cs group 89 versus 75 respectively p 0027 serious aes observed full cs group p 0017 incidences total aes p 0036 infections p 0024 lower lef group full cs groupconclusionslef combined halfdose cs superior fulldose cs treatment igan,0.0
involvement classic alternative nonhomologous end joining pathways hematologic malignancies targeting strategies treatment abstractchromosomal translocations main etiological factor hematologic malignancies translocations generally consequence aberrant dna doublestrand break dsb repair dsbs arise either exogenously endogenously cells repaired major pathways including nonhomologous endjoining nhej homologous recombination hr minor pathways alternative endjoining aej therefore defective nhej hr aej pathways force hematopoietic cells toward tumorigenesis components repair pathways overactivated various tumor entities targeting pathways cancer cells can sensitize especially resistant clones radiation chemotherapy agents however targeted therapybased studies currently underway area furtherly biological pitfalls clinical issues limitations related targeted therapies need considered review aimed investigate alteration dna repair elements cnhej aej hematologic malignancies evaluate potential targeted therapies pathways,0.0
zinc antagonizes ironregulation tyrosine hydroxylase activity dopamine production drosophila melanogaster background dopamine da neurotransmitter plays roles movement cognition attention reward responses deficient da signaling associated progression number neurological diseases parkinsons disease due critical functions da expression levels brain tightly controlled one important ratelimiting step biosynthetic pathway catalyzed tyrosine hydroxylase th enzyme uses iron ion fe2+ cofactor role metal ions additionally associated etiology parkinsons disease however way dopamine synthesis regulated vivo whether regulation metal ion levels component da synthesis fully understood analyze role catsup drosophila ortholog mammalian zinc transporter slc39a7 zip7 regulating dopamine levelsresultswe found catsup functional zinc transporter regulates intracellular zinc distribution er golgi cytosol lossoffunction catsup leads increased da levels showed increased dopamine production due reduction zinc levels cytosol zinc ion zn2+ negatively regulates dopamine synthesis direct inhibition th activity antagonizing fe2+ binding th thus rendering enzyme ineffective nonfunctionalconclusionsour findings uncovered previously unknown mechanism underlying control cellular dopamine expression normal levels dopamine synthesis maintained balance fe2+ zn2+ ions findings also provide support metal modulation possible therapeutic strategy treatment parkinsons disease dopaminerelated diseases,0.0
targeting ifn activity b cells plasmacytoid dendritic cells induces robust tolerogenic response protection eae sci rep 2021 nov 3 11 1 21575 doi 101038 s41598021008916abstracttype interferon ifn first drug approved treatment multiple sclerosis ms still frequently used first line therapy however systemic ifn also causes considerable side effects affecting therapy adherence dose escalation addition mechanism action ifn ms multifactorial still completely understood using actaferons activityontarget ifns afns optimized ifnbased immunocytokines allow cellspecific targeting previously demonstrated specific targeting ifn activity dendritic cells dcs can protect experimental autoimmune encephalitis eae inducing vivo tolerogenic protective effects evidenced increased indoleamine2 3dioxygenase ido transforming growth factor tgf release plasmacytoid p dcs improved immunosuppressive capacity regulatory t b cells report targeting type ifn activity specifically towards b cells also provides strong protection eae targeting pdcs using siglechafn can significantly add protective effect superior protection achieved simultaneous targeting b lymphocytes pdcs correlated improved il10 responses b cells conventional cdcs previously unseen robust ido response several cells including b t lymphocytes cdc1 cdc2pmid34732771 doi101038 s41598021008916,0.0
neurodegenerative diseases cholesterol seeing field players front aging neurosci 2021 nov 3 13766587 doi 103389 fnagi2021766587 ecollection 2021abstractneurodegenerative diseases namely alzheimers ad parkinsons pd huntingtons disease hd together amyotrophic lateral sclerosis als multiple sclerosis ms devastate millions lives per year worldwide impose increasing socioeconomic burden across nations consequently diseases occupy considerable portion biomedical research aiming understand mechanisms neurodegeneration develop efficient treatments potential culprit cholesterol serving essential component cellular membranes cofactor signaling pathways precursor oxysterols hormones article uncovers workforce studying research neurodegeneration cholesterol using teamtree analysis new bibliometric approach reveals history dynamics teams exposes key players based citationindependent metrics teamcentered view reveals players important field biomedical researchpmid34803658 pmcpmc8595328 doi103389 fnagi2021766587,0.0
hospitalization budget impact covid19 pandemic spain abstractobjectivesthe aim determine direct impact covid19 pandemic spains health budgetmethodsbudget impact analyses based retrospective data patients suspected severe acute respiratory syndrome coronavirus 2 sarscov2 admitted spanish hospital february 26 may 21 2020 direct medical costs perspective hospital calculated analyzed diagnostic tests drugs medical nursing care isolation ward icu stays three cohorts patients seen emergency room hospitalized patients tested positive sarscov2 patients tested negativeresultsthe impact hospitals budget 3 months calculated 15 633 180 974 related health care hospitalization icu stays accounted 53 total costs mean cost per patient 10 744 main costs staffing costs 10 131 11 357 patient physicians 10 274 11 215 patient nurses scenario analysis showed range hospital expenditure 14 693 256 16 524 924 median impact pandemic spanish health budget sensitivity analysis using bootstrapped individual data 9357 million interquartile range iqr 9071 9689 conservative scenario 113 588 hospital admissions 11 664 icu admissions 10 385 million iqr 110 030 10 758 worstcase scenario including suspected cases conclusionthe impact covid19 spanish public health budget 123 total public health expenditure greater multiple sclerosis cancer diabetes cost,0.0
differential hippocampal protein expression normal mice mice perioperative neurocognitive disorder proteomic analysis abstractobjectivesto compare differential expression protein hippocampal tissues mice perioperative neurocognitive disorder pnd normal control mice explore possible mechanism pndmethodsmice randomly divided pnd group n 9 control group n 9 mice pnd group treated open tibial fracture intramedullary fixation isoflurane anesthesia mice control group received pure oxygen without surgery cognitive functions two groups examined using morris water maze experiment open field test fear conditioning test protein expression hippocampus mice analyzed highperformance liquid chromatographymass spectrometry hplcms ms gene ontology go kyoto encyclopedia genes genomes kegg pathway enrichment analyses performed explore principal functions dysregulated proteinsresultsa total 21 proteins differentially expressed pnd control mice days 1 3 7 operation proteins involved many pathological processes neuroinflammatory responses mitochondrial oxidative stress impaired synaptic plasticity neuronal cell apoptosis also dysregulated proteins involved mapk ampk erbb signaling pathwaysconclusionthe occurrence pnd attributed multiple mechanisms,0.0
risk factors immunerelated adverse events learned lies ahead abstractimmune checkpoint inhibitors icis heralded advent new era oncology holding promise prolonged survival severe otherwise treatmentrefractory advanced cancers however remarkable antitumor efficacy agents overshadowed potential inducing autoimmune toxic effects collectively termed immunerelated adverse events iraes autoimmune adverse effects often difficult predict possibly permanent occasionally fatal hence identification risk factors iraes urgently needed allow prompt therapeutic intervention review discusses potential mechanisms iraes arise summarizes existing evidence regarding risk factors associated occurrence iraes particular examined available data regarding effect series clinicopathological demographic factors risk iraes,0.0
serum neurofilament light chain correlates myelin axonal magnetic resonance imaging markers multiple sclerosis abstractbackgroundneurofilaments cytoskeletal proteins detectable blood neuroaxonal injury multiple sclerosis ms disease progression greater lesion volume brain atrophy associated higher levels serum neurofilament light chain nfl studies examined relationship nfl advanced magnetic resonance imaging mri measures related myelin axons assessed relationship serum nfl brain mri measures diverse group ms participantsmethods materials103 participants 20 clinically isolated syndrome 33 relapsingremitting 30 secondary progressive 20 primary progressive underwent 3t mri obtain myelin water fraction mwf geometric mean t2 gmt2 water content t1 high angular resolution diffusion imaging hardi derived axial diffusivity ad radial diffusivity rd fractional anisotropy fa diffusion basis spectrum imaging dbsi derived ad rd fa restricted hindered water fiber fractions volume measurements normalized brain lesion thalamic deep grey matter gm cortical thickness multiple linear regressions assessed strength association serum nfl dependent variable mri measure whole brain wb normal appearing white matter nawm t2 lesions independent variables controlling age expanded disability status scale disease durationresultsserum nfl levels significantly associated metrics axonal damage fa r2wbhardi029 r2nawmhardi031 r2nawmdbsi030 r2lesiondbsi031 ad r2wbhardi031 myelin damage mwf r2wb029 r2nawm030 rd r2wbhardi032 r2nawmhardi034 r2lesiondbsi030 edema inflammation t1 r2lesion032 gmt2 r2wb031 r2lesion031 cellularity restricted fraction r2wb030 r2nawm032 across entire ms cohort higher serum nfl levels associated significantly higher t2 lesion volume r2035 lower brain structure volumes thalamus r2031 deep gm r2033 normalized brain r2031 smaller cortical thickness r2031 conclusionthe association nfl myelin mri markers suggest elevated serum nfl useful biomarker reflects acute axonal damage also damage myelin inflammation likely due known synergistic myelinaxon coupling relationship,1.0
mriderived gratio lesion severity newly diagnosed multiple sclerosis brain commun 2021 nov 3 3 4 fcab249 doi 101093 braincomms fcab249 ecollection 2021abstractmyelin loss associated axonal damage established multiple sclerosis relationship challenging study vivo early disease ask whether myelin loss associated axonal damage diagnosis combining noninvasive neuroimaging blood biomarkers performed quantitative microstructural mri singlemolecule elisa plasma neurofilament measurement 73 patients newly diagnosed immunotherapy nave relapsingremitting multiple sclerosis myelin integrity evaluated using aggregate gratios derived magnetization transfer saturation neurite orientation dispersion density imaging diffusion data found significantly higher gratios within cerebral white matter lesions suggesting myelin loss compared normalappearing white matter 061 versus 057 difference 0036 95 ci 00290043 p 0001 lesion volume spearmans rho rs 038 p 0001 gratio rs 024 p 005 correlated independently plasma neurofilament patients substantial lesion load n 38 higher gratio defined greater median likely abnormally elevated plasma neurofilament normal gratio defined less median 11 23 48 versus 2 15 13 p 005 data suggest even multiple sclerosis diagnosis reduced myelin integrity associated axonal damage mriderived gratio may provide useful additional information regarding lesion severity help identify individuals high degree axonal damage disease onsetpmid34877533 pmcpmc8643503 doi101093 braincomms fcab249,1.0
early treatment responses peginterferon beta1a associated longerterm clinical outcomes patients relapsingremitting multiple sclerosis subgroup analyses advance attain abstractbackground early intervention welltolerated diseasemodifying therapies dmts relapsingremitting multiple sclerosis rrms recommended order delay disease progression reduce neurologic damage preserve brain volume optimize longterm patient outcomes lack conversion new newly enlarging t2 net2 gadoliniumenhancing gd+ lesions chronic hypointensities black hole conversion achievement evidence disease activity neda early course treatment considered potential indicators treatment effect predictors longerterm clinical outcomesmethods patients rrms treated peginterferon beta1a 2year advance phase 3 clinical trial nct0090639 2year openlabel extension study attain nct01332019 grouped newly diagnosed diagnosed 1 year prior enrollment dmt naive nonnewly diagnosed analyses impact early treatment disease activity control newly diagnosed nonnewly diagnosed subgroups divided based whether initiated peginterferon beta1a every 2 weeks q2w starting study year 1 continuously treated peginterferon beta1a q2w every 4 weeks study year 2 delayed treatment patient subgroups evaluated conversion net2 gd+ lesions persistent black holes pbhs brain atrophy percentage change whole brain volume wbv achievement neda composite outcomes association disease activity measures longerterm clinical outcomes annualized relapse rate arr confirmed disability worsening cdw results 2 years significantly fewer pbhs developed net2 lesions gd+ lesions newly diagnosed nonnewly diagnosed patients continuously treated peginterferon beta1a corresponding delayedtreatment groups p00001 percentage decrease wbv 6 months rebaselined 2 years significantly lower newly diagnosed nonnewly diagnosed patients received continuous peginterferon beta1a treatment patients received delayed treatment p00442 study year 1 higher proportion newly diagnosed nonnewly diagnosed patients treated peginterferon beta1a treated placebo achieved neda newly diagnosed 283 vs 135 p00010 nonnewly diagnosed 408 vs 158 p00001 neda rates remained stable study years 24 newly diagnosed range 500539 nonnewly diagnosed range 544570 subgroups patients without pbh conversion significantly lower arr 2 years newly diagnosed p00109 nonnewly diagnosed p00044 lower proportion patients 12week cdw 2 years newly diagnosed p02787 nonnewly diagnosed p00045 corresponding patient subgroups pbh conversion patients achieved neda advance study years 12 significantly lower arr attain study years 34 patients achieve neda newly diagnosed p00003 nonnewly diagnosed p00001 4 years safety outcomes differ newly diagnosed nonnewly diagnosed patient subgroupsconclusions results indicate newly diagnosed nonnewly diagnosed patients treated continuously peginterferon beta1a q2w experienced better disease control time received delayed treatment patients neda evidence less radiological disease activity first 2 years treatment better longerterm clinical outcomes evidence greater disease activity,0.0
bruton#39 s tyrosine kinase btk inhibitors autoimmune diseases making sense btk inhibitor specificity profiles recent clinical trial successes failures front immunol 2021 nov 3 12662223 doi 103389 fimmu2021662223 ecollection 2021abstractclinical development btk kinase inhibitors treating autoimmune diseases lagged behind development drugs treating cancers due part concerns lack selectivity associated toxicity profiles first generation drug candidates used long term treatment immune mediated diseases second generation btk inhibitors made great strides limiting offtarget activities distantly related kinases though variable success limiting crossreactivity within closely related tec family kinases investigated btk specificity toxicity profiles drug properties disease associated signaling pathways clinical indications trial successes failures 13 btk inhibitor drug candidates tested phase 2 higher clinical trials representing 7 autoimmune 2 inflammatory immunemediated diseases focused rheumatoid arthritis ra multiple sclerosis ms systemic lupus erythematosus sle majority btk nonclinical clinical studies reported additional information pemphigus vulgaris pv sjogrens disease sj chronic spontaneous urticaria csu graft versus host disease gvhd asthma included available improved btk selectivity versus kinases outside tec family improved clinical toxicity profiles less profile distinction evident within tec family analysis genetic associations ra ms sle biomarkers tec family members revealed btk tec family members may drivers disease however mediators signaling pathways associated pathophysiology autoimmune diseases btk particular may associated b cell myeloid differentiation well autoantibody development implicated immune mediated diseases successes clinic treating ra ms pv itp gvhd sle sj support concept btk plays important role mediating pathogenic processes amenable therapeutic intervention depending disease based data collected study propose current compound characteristics btk inhibitor drug candidates treatment autoimmune diseases achieved selectivity safety coverage requirements necessary deliver therapeutic benefitpmid34803999 pmcpmc8595937 doi103389 fimmu2021662223,0.0
clinicallycompatible workflow computeraided assessment brain disease activity multiple sclerosis patients front med lausanne 2021 nov 3 8740248 doi 103389 fmed2021740248 ecollection 2021abstractover last 10 years number approved disease modifying drugs acting focal inflammatory process multiple sclerosis ms increased 3 10 wide choice offers opportunity personalized medicine objective clinical radiological activity patient new paradigm requires optimization detection new flair lesions longitudinal mri paper describe complete workflowthat developed implemented deployed evaluatedto facilitate monitoring new flair lesions longitudinal mri ms patients workflow designed usable hospital private neurologists radiologists france consists three main components software component allows automated secured anonymization transfer mri data clinical picture archive communication system pacs processing server viceversa ii fully automated segmentation core enables detection focal longitudinal changes patients t1weighted t2weighted flair brain mri scans iii dedicated web viewer provides intuitive visualization new lesions radiologists neurologists first present different components evaluate workflow 54 pairs longitudinal mri scans analyzed 3 experts 1 neuroradiologist 1 radiologist 1 neurologist without proposed workflow show workflow provided valuable aid clinicians detecting new ms lesions terms accuracy mean number detected lesions per patient per expert 18 without workflow vs 23 workflow p 5104 time dedicated experts mean time difference 245 p 104 increase number detected lesions implications classification ms patients stable active even experienced neuroradiologist mean sensitivity 074 without workflow 090 workflow pvalue difference 0003 therefore potential consequences therapeutic management ms patientspmid34805206 pmcpmc8595265 doi103389 fmed2021740248,0.0
prevalence vitamin d deficiency associated risk factors among rural population northern part persian gulf background accumulating evidence indicates vitamin d deficiency increased globally last two decades however majority studies concerned cities scant information regarding prevalence vitamin d rural areas main aim study investigate prevalence vitamin d deficiency associated risk factors among rural population bushehr province shares longest border persian gulfmethodsthe rural inhabitants 25 years old three mountainous plain seashore areas bushehr province selected stratified multicluster random sampling method obtaining participants demographic anthropometric data past medical history serum 25hydroxyvitamin d 25 oh d measured using elisaresultsa total 1806 means sd 46 14years old rural subjects 35 males 65 females participated study prevalence vitamin d deficiency insufficiency sufficiency 28 50 22 respectively deficiency vitamin d women higher men or127 95 ci 105 154 p004 positive significant correlation age serum vitamin d levels men vitamin d deficiency higher bmi p0008 association observed among women p07 significant difference food items consumption frequencies vitamin d status p005 mountainous plain areas highest lowest vitamin d levels respectivelyconclusionsalthough bushehr province located sunny part iran prevalence vitamin d deficiency high among rural population shift lifestyle patterns rapid industrialization rural areas may responsible therefore enrichment dietary sources vitamin d use vitamin d supplements recommended tackle high prevalence vitamin d deficiency rural population northern part persian gulf,0.0
reduced risk recurrent pneumothorax sirolimus therapy surgical pleural covering entire lung lymphangioleiomyomatosis background patients lymphangioleiomyomatosis lam frequently experience pneumothorax although sirolimus standard therapy lam effect pneumothorax controversial recently total pleural covering tpc modified tpc mtpc introduced surgical treatment options pneumothorax patients lam however effect sirolimus recurrence pneumothorax patients underwent treatments still uncertain hypothesized clinical factors including sirolimus treatment predict postoperative recurrence pneumothorax order clarify hypothesis retrospectively analyzed clinical data 18 consecutive patients lam underwent 24 surgical pleural covering entire lung spc 17 tpc 7 mtpc pneumothoraces surgical database january 2005 january 2019 determined predictors postoperative recurrenceresultsof 24 surgeries spc 14 surgeries 583 history two ipsilateral pneumothoraces 11 surgeries 458 history ipsilateral pleural procedures spc sixteen surgeries 666 12 patients received treatment sirolimus spc sirolimus group median followup time 690 months spc four surgeries 166 three patients postoperative recurrence 5year recurrencefree survival rfs spc 829 patients postoperative recurrence serum level vascular endothelial growth factors d significantly higher nonrecurrence 32605 vs 8927 pg ml p 002 rate sirolimus treatment recurrence group significantly lower norecurrence group 0 vs 80 p 0006 logrank test showed rfs sirolimus group sirolimus use spc significantly better nonsirolimus group p 0001 significant difference observed factorsconclusionwe first reported sirolimus might effectively suppress recurrence pneumothoraces lam patients received spc sirolimus induction spc tpc mtpc might feasible option frequent pneumothorax lam,0.0
can covid19 exacerbate multiple sclerosis symptoms case series analysis abstractintroduction peripheral inflammation can exacerbate preexisting lesions central nervous system cns context neurodegenerative diseases including multiple sclerosis ms objective analyze clinical effect covid19 infection generator peripheral inflammation ms patients groupmethods retrospective analysis 400 medical records ms patients referral center carried ms patients presented covid19 surveyed symptoms exacerbation type duration onset exacerbation previous vaccination covid19 ms severity clinical demographic information medical records included descriptive inferential analysis performed using graphpad prism v6results 41 patients included 61 n25 reported neurological worsening 97 n4 relapses 73 n3 required corticosteroids found significant differences edss patients exacerbated ms symptoms p003 performing multivariate regression analysis found edss independently associated presence exacerbations ms context sarscov2 infection or244 p0022 conclusions preliminary study suggests covid19 infection trigger exacerbations ms symptoms new studies needed elucidate relationship covid19 ms,0.0
tensor electrical impedance myography identifies clinically relevant features amyotrophic lateral sclerosis physiol meas 2021 sep 14 doi 101088 13616579 ac2672 online ahead printabstractobjective electrical impedance myography eim shows promise effective biomarker amyotrophic lateral sclerosis als eim applies multiple input frequencies characterise muscle properties often via multiple electrode configurations herein assess nonnegative tensor factorisation can provide framework identifying clinically relevant features within high dimensional eim datasetapproach eim data recorded tongue healthy als diseased individuals resistivity reactivity measurements made 14 frequencies three electrode configurations gives 84 2 14 3 distinct data points per participant nonnegative tensor factorisation ntf applied dataset dimensionality reduction termed tensor eim significance tests symptom correlation classification approaches explored compare ntf using raw data feature selectionmain results tensor eim provides highly significant differentiation healthy als patients p 0001 auroc078 similarly tensor eim differentiates mild severe disease states p 0001 auroc075 significantly correlates symptoms 07 p 0001 trend centre frequency shifting right identified diseased spectra line electrical changes expected following muscle atrophysignificance tensor eim provides clinically relevant metrics identifying als related muscle disease procedure advantage using whole spectral dataset reduced risk overfitting process identifies spectral shapes specific disease allowing deeper clinical interpretationpmid34521070 doi101088 13616579 ac2672,0.0
dmannose suppresses oxidative response blocks phagocytosis experimental neuroinflammation proc natl acad sci u s 2021 nov 2 118 44 e2107663118 doi 101073 pnas2107663118abstractinflammation drives pathology many neurological diseases dmannose found exert antiinflammatory effect peripheral diseases effects neuroinflammation inflammatory cells central nervous system studied aimed determine effects dmannose key macrophage microglial functionsoxidative stress phagocytosis murine experimental autoimmune encephalomyelitis eae found dmannose improved eae symptoms compared phosphatebuffered saline pbs control mice monosaccharides multiagent molecular mri performed assess oxidative stress targeting myeloperoxidase mpo using mpobis5hydroxytryptamide diethylenetriaminepentaacetate gadolinium gd phagocytosis using crosslinked iron oxide clio nanoparticles vivo revealed dmannosetreated mice smaller total mpogd+ areas pbscontrol mice consistent decreased mpomediated oxidative stress interestingly dmannosetreated mice exhibited markedly smaller clio+ areas much less t2 shortening effect clio+ lesions compared pbscontrol mice revealing dmannose partially blocked phagocytosis vitro experiments different monosaccharides confirmed dmannose treatment blocked macrophage phagocytosis dosedependent manner phagocytosis myelin debris known increase inflammation decreasing phagocytosis result decreased activation proinflammatory macrophages indeed compared pbscontrol eae mice dmannosetreated eae mice exhibited significantly fewer infiltrating macrophages activated microglia among proinflammatory macrophages microglia greatly reduced antiinflammatory macrophages microglia increased uncovering dmannose diminishes proinflammatory response boosts antiinflammatory response findings suggest dmannose overthecounter supplement high safety profile may lowcost treatment option neuroinflammatory diseases multiple sclerosispmid34702739 doi101073 pnas2107663118,1.0
polyclonal aptamers specific fluorescence labeling quantification health relevant human gut bacterium parabacteroides distasonis microorganisms 2021 nov 2 9 11 2284 doi 103390 microorganisms9112284abstractsinglestranded dna aptamers affinity molecules rapid reliable detection intestinal bacteria particular interest equip health systems novel robust cheap diagnostic tools monitoring success supplementation strategies selected probiotic gut bacteria fight major widespread threats obesity neurodegenerative diseases human gut bacterium parabacteroides distasonis p distasonis positively associated diseases obesity nonalcoholic fatty liver disease multiple sclerosis reduced cell counts diseases thus promising potential probiotic bacterium future microbial supplementation paper report evolution specific polyclonal aptamer library fluorescence based flucellselex directed whole cells p distasonis specifically efficiently binds labels p distasonis aptamer library showed high binding affinity suited quantitatively discriminate p distasonis prominent gut bacteria also mixtures believe library promising probiotic bacterium prototype may open new routes towards development novel biosensors easy efficient quantitative monitoring microbial abundance human microbiomes generalpmid34835410 doi103390 microorganisms9112284,0.0
development internal validation disability algorithm multiple sclerosis administrative data front neurol 2021 nov 2 12754144 doi 103389 fneur2021754144 ecollection 2021abstractobjective developed internally validated algorithm disability status multiple sclerosis ms using administrative data methods linked administrative data manitoba canada clinical dataset expanded disability status scale edss scores people ms clinical edss scores constituted reference standard created candidate indicators using administrative data included indicators based use particular health care services home care longterm care rehabilitation admission use specific diagnostic codes spasticity quadriplegia codes based use employment income insurance developed algorithms predict severe disability edss 60 predict disability continuous measure manually developed algorithms also employed regression approaches selected preferred algorithms disability tested association health care use due cause infection potential confounders results linked clinical administrative data 1 767 persons ms women living urban areas individual indicators tested specificities 90 severe disability diagnosis visual disturbance positive predictive values ppv 70 combination home care longterm care use rehabilitation admission sensitivity 619 specificity 9076 ppv 7006 negative predictive 8721 based regression modeling bestperforming algorithm predicting edss continuous variable included age home care use longterm care admission admission rehabilitation visual disturbance paralytic syndromes spasticity mean difference observed predicted values edss 00644 95ci 01632 00304 greater disability whether measured using clinical edss either administrative data algorithms similarly associated increased hospitalization rates due cause infection conclusion developed internally validated algorithm disability ms using administrative data may support populationbased studies wish account disability status access clinical data sources information also found severe disability associated increased health care use including due infectionpmid34795632 pmcpmc8592934 doi103389 fneur2021754144,0.0
circulating mirnas potential biomarkers distinguishing relapsingremitting secondary progressive multiple sclerosis review int j mol sci 2021 nov 2 22 21 11887 doi 103390 ijms222111887abstractmultiple sclerosis ms debilitating neurodegenerative highly heterogeneous disease variable course common ms subtype relapsingremitting rr interchanging periods worsening relative stabilization decade rr patients alters secondary progressive sp phase debilitating one clear remissions leading progressive disability deterioration among greatest challenges clinicians understanding disease progression molecular mechanisms since rr mainly characterized inflammatory processes sp neurodegeneration prevails especially important distinguishing rr sp subtype early will enable faster implementation appropriate treatment currently ms course wellcorrelated biomarkers routinely used clinical practice despite many studies still reliable indicators correlating disease stage activity degree circulating micrornas mirnas may considered valuable molecules ms diagnosis presumably helpful predicting disease subtype mirna expression dysregulation commonly observed ms course moreover knowledge diverse mirna panel expression rrms spms may allow deterring disability progression successful treatment therefore review address current state research differences mirna panel expression phasespmid34769314 doi103390 ijms222111887,0.0
sulfonylurea receptor 1 central nervous system injury updated review int j mol sci 2021 nov 2 22 21 11899 doi 103390 ijms222111899abstractsulfonylurea receptor 1 sur1 member adenosine triphosphate atp binding cassette abc protein superfamily encoded abcc8 recognized key mediator central nervous system cns cellular swelling via transient receptor potential melastatin 4 trpm4 channel discovered approximately 20 years ago channel normally absent cns transcriptionally upregulated cns injury comprehensive review pathophysiology role sur1 cns published 2012 since breadth depth understanding involvement channel secondary injury undergone exponential growth sur1trpm4 inhibition shown decrease cerebral edema hemorrhage progression multiple preclinical models well early clinical studies across range cns diseases including ischemic stroke traumatic brain injury cardiac arrest subarachnoid hemorrhage spinal cord injury intracerebral hemorrhage multiple sclerosis encephalitis neuromalignancies pain liver failure status epilepticus retinopathies hivassociated neurocognitive disorder given substantial developments combined timeliness ongoing clinical trials sur1 inhibition now another decade later review advances pertaining sur1trpm4 pathobiology spectrum cns diseaseproviding overview journey patchclamp experiments phase iii trialspmid34769328 doi103390 ijms222111899,0.0
allogeneic vs autologous mesenchymal stem#x2f stromal cells medication practice abstractmesenchymal stem stromal cell msc based therapeutics already available treatment range diseases medical conditions autologous allogeneic mscs obtained self donors advantages disadvantages medical practice therapeutic benefits using autologous vs allogeneic mscs inconclusive transplanted mscs within body interact physical microenvironment niche physiologically pathologically cells newly established tissue microenvironment may impacted pathological harmful environmental factors alter unique biological behaviors meanwhile temporary microenvironment niche may also altered resident nichesurrounding mscs therefore functional plasticity heterogeneity mscs caused different donors subpopulations mscs may result potential uncertainty safe efficacious medical practice acknowledging connection mscs biology existing microenvironment donorcontrolled clinical practice longterm therapeutic benefit suggested consider minimizing mscs potential harm mscbased individual therapies review summarize advantages disadvantages autologous vs allogeneic mscs therapeutic applications among issues highlight importance better understanding various microenvironments may affect properties nichesurrounding mscs discuss clinical applications mscs within different contexts treatment different diseases including cardiomyopathy lupus lupus nephritis diabetes diabetic complications bone cartilage repair cancer tissue fibrosis,0.0
optimisation maintenance delivery systems cytostatic medicines background realworld application maintenance organisations brings together number maintenance policies order achieve desired availability efficiency profitability however literature mostly chooses single maintenance policy decision process suited real conditions company applied study takes combination maintenance policies alternatives conforms actual practice maintenance organisations furthermore introduces possibility including extra spare parts outsourcing maintenance policies although selection maintenance policies applied many kinds business machine almost instance application hospitals never applied delivery systems cytostatic drugsmethodsthe model uses fuzzy technique order preference similarity ideal solution topsis recognised highly suitable solving group decisionmaking problems fuzzy environment fuzzy set theory also considered proficient crisp numbers handling ambiguity imprecisions data scarcity uncertainty inherent decisions made human beings judgements required obtained decision group comprising heads facilities maintenance maintenance medical equipment health safety work environment programmingadmission group also included care staff specifically heads main clinical services medical supervisors model includes original criteria quality health care measures impact care function mean availability alternative also considers impact hospital management via criteria working environment organisation impact health care former criterion measures equality among care services hospital latter assesses effect regional health cover model built using real data obtained state hospital spain model can also easily applied national international healthcare organisations providing weights specific criteria produced decision group healthcare organisation alternatives updated accordance considered important hospitalresultsthe results obtained model recommend changing alternative currently use corrective preventive maintenance corrective preventive maintenance plus two spare hoods alternative lead availability 1 highest possible systems preparing personalised cytotoxic drugs quality service therefore high additionally offer services users hospital also offer cover preparation cytotoxic medicines hospitals catchment areaconclusionsthe results suggest possibility improvements support logistical systems include maintenance traditionally held effect quality care may key improving care quality also reducing risk patients care noncare staff environment,0.0
p62 accumulates neuroanatomical circuits response tauopathy propagation abstractin alzheimers disease related tauopathies transsynaptic transfer accumulation pathological tau donor recipient neurons thought contribute disease progression underlying mechanisms poorly understood using complementary vivo vitro models examined relationship two processes neuronal clearance accumulation p62 marker defective protein clearance correlated pathological tau accumulation two mouse models tauopathy spread entorhinal cortextau ectau mice tau pathology progresses time ec brain regions ps19 mice injected tau seeds models several brain regions p62 colocalized human tau pathological conformation mc1 antibody ectau mice p62 accumulated overt tau pathology developed associated presence aggregationcompetent tau seeds identified using fretbased assay furthermore p62 accumulated cytoplasm neurons dentate gyrus ectau mice prior appearance mc1 positive tauopathy however mc1 positive tau shown present synapse colocalize p62 shown immuno electron microscopy vitro p62 colocalized tau inclusions two primary cortical neuron models tau pathology threechamber microfluidic device containing neurons overexpressing fluorescent tau seeding tau donor chamber led tau pathology spread p62 accumulation donor recipient chamber overall data accordance hypothesis accumulation transsynaptic spread pathological tau disrupts clearance mechanisms preceding appearance obvious tau aggregation vicious cycle tau accumulation clearance deficit expected feedforward exacerbate disease progression across neuronal circuits human tauopathies,0.0
impact diseasemodifying therapies mri neurocognitive outcomes relapsingremitting multiple sclerosis protocol systematic review network metaanalysis bmj open 2021 nov 2 11 11 e051509 doi 101136 bmjopen2021051509abstractintroduction diseasemodifying therapies dmts mainstay treatment relapsingremitting multiple sclerosis rrms established evidence dmts effective reducing relapse rate disease progression rrms less consideration synthesis mri neurocognitive outcomes play increasingly important role treatment decisions aim systematic review network metaanalysis examine relative efficacy acceptability tolerability dmts rrms using mri neurocognitive outcomesmethods analysis will search electronic databases including medline embase cochrane central register controlled trials date restrictions will also search websites international regulatory bodies pharmaceuticals international trial registries will include parallel group randomised controlled trials dmts including interferon beta1a intramuscular interferon beta1a subcutaneous interferon beta1b peginterferon beta1a glatiramer acetate natalizumab ocrelizumab alemtuzumab dimethyl fumarate teriflunomide fingolimod cladribine ozanimod mitoxantrone rituximab either headtohead placebo adults rrms primary outcomes include efficacy mri outcomes including new t1 hypointense lesions t2 hyperintense lesions acceptability allcause dropouts secondary outcomes include gadoliniumenhancing lesions cerebral atrophy tolerability dropouts due adverse events neurocognitive measures across three domains including processing speed working memory verbal learning will included exploratory outcomes data will analysed using randomeffects pairwise metaanalysis bayesian hierarchical random effects network metaanalysis evaluate efficacy acceptability tolerability included dmts subgroup sensitivity analyses will conducted assess robustness findings review will reported using preferred reporting items systematic reviews incorporating network metaanalyses statementethics dissemination protocol require ethics approval results will disseminated peerreviewed academic journalprospero registration number crd42021239630pmid34728450 doi101136 bmjopen2021051509,0.0
cold exposure protects neuroinflammation immunologic reprogramming cell metab 2021 oct 19s15504131 21 004800 doi 101016 jcmet202110002 online ahead printabstractautoimmunity energetically costly impact metabolically active state immunity immunemediated diseases unclear ly6chi monocytes key effectors cns autoimmunity elusive role priming naive autoreactive t cells provide unbiased analysis immune changes various compartments cold exposure show energetically costly stimulus markedly ameliorates active experimental autoimmune encephalomyelitis eae cold exposure decreases mhcii monocytes steady state various inflammatory mouse models suppresses t cell priming pathogenicity modulation monocytes genetic antibodymediated monocyte depletion adoptive transfer th1 th17polarized cells eae abolishes coldinduced effects t cells eae respectively findings provide mechanistic link environmental temperature neuroinflammation suggest competition coldinduced metabolic adaptations autoimmunity energetic tradeoff beneficial immunemediated diseasespmid34687652 doi101016 jcmet202110002,0.0
therapeutic maps sensorbased evaluation deep brain stimulation programming biomed tech berl 2021 nov 1 doi 101515 bmt20200210 online ahead printabstractprogramming deep brain stimulation dbs labourintensive process treating advanced motor symptoms specifically patients medicationrefractory tremor multiple sclerosis ms wearable sensors able detect manifestations pathological signs intention tremor ms however methods needed visualise response tremor dbs parameter changes clinical setting patients perform motor task fingertonose end attended dbs programming sessions ms patient intention tremor effectively quantified acceleration amplitude frequency new method introduced results generation therapeutic maps systematic review programming procedure dbs maps visualise combination tremor acceleration power clinical rating scores total electrical energy delivered brain possible side effects therapeutic maps yet employed lead certain degree standardisation objective decisions dbs settings maps provide base future research visualisation tools assist physicians frequently encounter patients dbs therapypmid34727584 doi101515 bmt20200210,0.0
interleukin6 evolving role management neuropathic pain neuroimmunological disorders background neuropathic pain neuroimmunological disorders refers pain caused lesion disease somatosensory system multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd ms nmosd autoimmune disorders central nervous system 50 patients disorders experience chronic neuropathic pain currently available medications management neuropathic pain limited effectiveness patients ms nmosd unmet medical need identify novel therapies management chronic neuropathic pain patients review article summarize role interleukin6 il6 pathogenesis ms nmosd ameliorative effects antiil6 therapies mouse models experimental autoimmune encephalomyelitis eae main bodyintraperitoneal injection mr161 antiil6 receptor il6r antibody reduced mechanical allodynia spontaneous pain eae mice attributed reduction microglial activation inhibition descending pain inhibitory system effect antiil6 therapies ameliorating neuropathic pain clinical setting controversial reduction pain intensity reported antiil6 antibody four studies namely case report pilot study retrospective observational study case series pain intensity evaluated using numerical rating scale nrs lower score indicating lesser pain reduction nrs score reported four studies however two randomized controlled trials another antiil6r antibody change visual analog scale pain score statistically significantly different compared placebo attributed low mean pain score baseline trials concomitant use medications pain one trials may masked effects antiil6r antibody neuropathic painconclusionthus antiil6 therapies might potential reduce neuropathic pain investigations warranted clarify effect inhibition il6 signaling neuropathic pain associated ms nmosd,0.0
hiv1 env enable development protective broadly neutralizing antibodies experimental autoimmune encephalomyelitis mouse model front immunol 2021 nov 2 12771359 doi 103389 fimmu2021771359 ecollection 2021abstractrecent studies showed immunological tolerance may restrict development envspecific autoreactive broadly neutralizing antibodies evidence consistent finding env immunization systemic lupus erythematosus sle murine model produced antibodies neutralize tier 2 hiv1 strains study address possibility eliciting neutralizing antienv antibodies autoimmune diseases multiple sclerosis ms reported sle showed first time small number hiv1 negative relapsing remitting ms patients exhibited antibodies neutralizing properties attempts inducing antibodies eae mouse model ms failed success eliciting envspecific neutralizing antibodies might related specific characteristics autoimmune disease might rely improving vaccination design studies using mouse models useful gain insight hivspecific neutralizing antibody responses regulated order develop protective hiv1 vaccinepmid34795677 pmcpmc8593332 doi103389 fimmu2021771359,1.0
safety tolerability activity mesenchymal stem cells versus placebo multiple sclerosis mesems phase 2 randomised doubleblind crossover trial summarybackgroundmesenchymal stem cells mscs also known mesenchymal stromal cells proposed promising therapeutic option people multiple sclerosis basis immunomodulatory neuroprotective properties mesenchymal stem cells multiple sclerosis mesems study devised evaluate safety tolerability activity autologous mscs derived bone marrow infused intravenously patients active multiple sclerosismethodsmesems randomised phase 2 trial done 15 sites nine countries patients aged 1850 years active relapsingremitting progressive multiple sclerosis included disease duration 215 years since onset multiple sclerosis expanded disability status scale score 2565 patients randomly assigned 11 according crossover design receive single intravenous dose autologous bone marrowderived mscs followed placebo week 24 receive placebo followed autologous mscs week 24 followup visit week 48 primary objectives test safety activity msc treatment primary safety endpoint assess number severity adverse events within treatment arm primary efficacy endpoint number gadoliniumenhancing lesions gels counted week 4 12 24 compared treatment groups primary efficacy endpoint assessed full analyis set participants completed week 24 visit efficacy endpoints evaluated using predefined statistical testing procedure safety monitored throughout study recording vital signs adverse events visitfindingsfrom july 16 2012 july 31 2019 144 patients randomly assigned first receive early intravenous infusion autologous bone marrowderived mscs n69 placebo n75 msc treatment meet primary endpoint efficacy total number gels accumulated baseline week 24 rate ratio rr 094 95 ci 058150 p078 213 adverse events recorded similarly distributed groups 93 cases recorded 35 51 69 patients treated first mscs vs 120 cases 42 56 75 patients infused first placebo frequent adverse events reported infection infestations total 54 25 213 adverse events 18 19 93 earlymsc group 36 30 120 delayedmsc group nine serious adverse events reported seven patients treated placebo versus none msc group serious adverse events considered unrelated treatment infusion deaths reported studyinterpretationbone marrowderived msc treatment safe well tolerated show effect gels mri surrogate marker acute inflammation patients active forms multiple sclerosis week 24 thus study support use bone marrowderived mscs treat active multiple sclerosis studies address effect mscs parameters related tissue repairfundingfondazione italiana sclerosi multipla fism european committee treatment research multiple sclerosis ectrims multiple sclerosis international federation msif centralised activities individual trials participating mesems network funded following agencies fism compagnia di san paolo italy danish multiple sclerosis society toyota foundation danish blood donorsnull research foundation denmark spanish health research institute carlos 3 andalusian public foundation progreso y salud spain royan institute stem cell biology technology iran spinal cord injury tissue regeneration centre salzburg paracelsus medical university salzburg austria fondation pour lnullaide la recherche sur la sclrose en plaques arsep french muscular dystrophy association afm telethon france uk multiple sclerosis society uk stem cell foundation uk multiple sclerosis society canada multiple sclerosis scientific research foundation research manitoba canada,1.0
grp78 antibodies associated bloodbrain barrier breakdown antimyelin oligodendrocyte glycoprotein antibodyassociated disorder neurol neuroimmunol neuroinflamm 2021 nov 1 9 1 e1038 doi 101212 nxi0000000000001038 print 2022 janabstractbackground objectives analyze 1 effect immunoglobulin g igg patients antimyelin oligodendrocyte glycoprotein antibody mogab associated disorder bloodbrain barrier bbb endothelial cells 2 positivity glucoseregulated protein 78 grp78 antibodies mogabassociated disordersmethods igg purified sera patients mogabassociated disorder acute phase acute mog n 15 stable stage stable mog n 14 healthy controls hcs n 9 disease controls dcs n 27 human brain microvascular endothelial cells bmecs incubated igg number nuclear nfb p65positive cells bmecs using highcontent imaging system quantitative messenger rna change gene expression whole transcriptome using rnaseq analyzed grp78 antibodies patient iggs detected western blottingresults igg acute mog group significantly induced nuclear translocation nfb increased vascular cell adhesion molecule 1 intercellular adhesion molecule 1 expression permeability 10kda dextran compared stable mog hc dc groups rnaseq pathway analysis revealed nfb signaling oxidative stress nqo1 play key roles nqo1 nrf2 protein amounts significantly decreased exposure igg acute mog group rate grp78 antibody positivity acute mog group 10 15 67 95 confidence interval 3888 significantly higher stable mog group 5 14 36 1365 multiple sclerosis group 4 29 14 432 dcs 3 27 11 229 hcs 0 9 0 removal grp78 antibodies mogigg reduced effect nfb nuclear translocation increased permeabilitydiscussion grp78 antibodies may associated bbb dysfunction mogabassociated disorderpmid34725263 doi101212 nxi0000000000001038,1.0
mechanistic dissection dominant aire mutations mouse models reveals aire autoregulation j exp med 2021 nov 1 218 11 e20201076 doi 101084 jem20201076 epub 2021 sep 3abstractthe autoimmune regulator aire essential establishment central tolerance prevention autoimmunity interestingly different aire mutations cause autoimmunity either recessive dominantnegative manners using engineered mouse models establish monoallelic mutants including c311y c446g cause breakdown central tolerance using rnaseq atacseq chipseq protein analyses dissect underlying mechanisms dominancy specifically show recessive mutations result lack aire protein expression dominant mutations phd domains augment expression dysfunctional aire altered capacity bind chromatin induce gene expression finally demonstrate enhanced aire expression partially due increased chromatin accessibility aire proximal enhancer serves docking site aire binding therefore data elucidate aire mutations recessive others dominant also identify autoregulatory mechanism aire negatively modulates expressionpmid34477806 doi101084 jem20201076,0.0
phase separation toxicity c9orf72 poly pr depends alternate distribution arginine j cell biol 2021 nov 1 220 11 e202103160 doi 101083 jcb202103160 epub 2021 sep 9abstractarg r rich dipeptide repeat proteins dprs poly pr proarg poly gr glyarg encoded hexanucleotide expansion c9orf72 gene induce neurodegeneration amyotrophic lateral sclerosis als although rrich dprs undergo liquidliquid phase separation llps affects multiple biological processes mechanisms underlying llps dprs remain elusive using silico vitro cellulo methods determined distribution charged arg residues regulates complex coacervation anionic peptides nucleic acids proteomic analyses revealed alternate arg distribution poly pr facilitates entrapment proteins acidic motifs via llps transcription translation diffusion nucleolar nucleophosmin npm1 impaired poly pr alternate charge distribution poly pr variants consecutive charge distribution propose pathogenicity rrich dprs mediated disturbance proteins entrapment phaseseparated droplets via sequencecontrolled multivalent proteinprotein interactionspmid34499080 doi101083 jcb202103160,0.0
multiple sclerosis meets systems immunology authors#39 reply ,0.0
multiple sclerosis meets systems immunology review 1 amit baror rui li argue autoimmune diseases like multiple sclerosis arise perturbations cellular networks resulting disbalance proinflammatory antiinflammatory mechanisms disbalance potentially enables spontaneous stabilisation exacerbation disease activity observed relapsing multiple sclerosis underlying immune processes partly stochastic yet shaped multitude genetic environmental influencesthe concept immune disbalance belongs wider context systems immunology2 systems immunology leverages rapidly expanding knowledge components immune system reached new level advent singlecell technologies begun revolutionise biomedicine3 example singlecell rna sequencing can identify genomewide transcriptome cell providing profound insights cellular lineage relationships differentiation pathways activation states information integrated genomic epigenomic proteomic metabolomic data multiomic approach 3 cellular elements therefore whole immune system can described terms multilayered networks single cells can isolated human blood accessible body fluids tissues systems immunology approaches hold particular promise human immunology medicine4baror li optimistic new technologies systems approaches will pave way personalised therapies dream might come true future now keep mind fundamental questions multiple sclerosis research yet answeredregarding causes multiple sclerosis one like know state disbalance initiated first place triggered epsteinbarr virus infection change microbiome low serum vitamin d concentrations environmental factors uniform trigger mechanism vary patientsregarding immunological markers antigens targeted autoreactive t cells b cells discovery autoantibodies aquaporin4 myelin oligodendrocyte glycoprotein led identification two new disease entities5 contrast uniform pathogenic autoantigen still missing multiple sclerosis unique antigenic target exist multiple sclerosis heterogeneous regard antigen reactivityregarding progressive multiple sclerosis can tackle vexingly complex association neuroinflammation neurodegeneration can systems immunology integrated systems neurobiology help unravel complexityi declare competing interests,1.0
understanding role blood brain barrier peripheral inflammation behaviour pathology ongoing confined cortical lesions abstractbackground inflammation central nervous system cns associated blood brain barrier bbb breakdown early stages multiple sclerosis ms indicating facilitated entry waves inflammatory cells circulation cns progressive forms ms lesion becomes chronic inflammation remains trapped within cns compartment forming slow evolving lesion characterized low inflammation microglia activation lesions edges chronic expression interleukin 1 il1 cortex induces bbb breakdown demyelination neurodegeneration microglial macrophage activation impaired cognitive performance latter can improved long bbb recovers lesion presents low inflammation study effects peripheral inflammation cortical central lesions restoration bbb order elucidate role peripheral inflammation lesions intact bbb occurs progressive forms msmaterials methods cortical lesions peripheral inflammation induced chronic expression il1 using adenovector performed histological immunohistochemistry brain tissue behavioural analysesresults effects chronic expression il1 cortex resolved within 56 days however peripheral sustained inflammation reopened bbb allowing reappearance neuroinflammatory processes within cortical lesions increased demyelination neurodegeneration increase behavioral symptoms cognitive impairment anxietylike symptomsconclusions early treatment peripheral inflammatory processes considered order protect brain exacerbation ongoing neurodegenerative process,1.0
mesenchymal stem cells multiple sclerosis hype hope search new approaches treat even cure multiple sclerosis several forms cellbased therapies explored including haematopoietic stem cells mesenchymal stem cells oligodendrocyte progenitor cells past 15 years several small uncontrolled trials assessed safety feasibility approaches using mesenchymal stem cells derived diverse tissues eg bone marrow adipose tissue placenta different routes administration eg intravenous intrathecal various outcome measures eg clinical neurophysiological mribased measures petrou colleagues 2 randomised doubleblind placebocontrolled trial investigate safety efficacy bone marrowderived mesenchymal stem cells patients progressive multiple sclerosis following complex crossover design 48 patients secondary progressive n41 primary progressive n7 multiple sclerosis received mesenchymal stem cells placebo via intravenous intrathecal injection results positive primary efficacy outcome based expanded disability status scale met 2 significantly fewer patients treatment failure groups treated mesenchymal stem cells intrathecally 67 intravenously 97 shamtreated group 419 p00003 vs intrathecal administration p00008 vs intravenous administration 2 patients mri activity received mesenchymal stem cells intrathecally showed largest benefit 2,1.0
cumulative roles epsteinbarr virus human endogenous retroviruses human herpes virus6 driving inflammatory cascade underlying ms pathogenesis front immunol 2021 nov 1 12757302 doi 103389 fimmu2021757302 ecollection 2021abstractroles viral infections aberrant immune responses driving localized neuroinflammation neurodegeneration multiple sclerosis ms focus intense research epsteinbarr virus ebv persistent frequently reactivating virus major immunogenic influences near 100 epidemiological association ms considered play leading role ms pathogenesis triggering localized inflammation near within central nervous system cns triggering may occur directly via viral products rna protein indirectly via antigenic mimicry involving bcells tcells cytokineactivated astrocytes microglia cells damaging myelin sheath neurons genetic msrisk factor hladr2b drb11501 dra10101 may contribute aberrant ebv antigenpresentation antiebv reactivity also mimicryinduced autoimmune responses characteristic ms central role proposed inflammatory eber1 ebvmirna lmp1 containing exosomes secreted viable reactivating ebv+ bcells repetitive release ebna1dna complexes apoptotic ebv+ bcells forming reactive immune complexes ebna1igg complement may accompanied cytokine ebvinduced expression human endogenous retrovirusw k hervw k elements possibly activation human herpesvirus6a hhv6a earlystage cns lesions contributing inflammatory cascade causing relapsingremitting neuroinflammatory progressive features characteristic ms elimination ebvcarrying bcells antibody ebvspecific tcell therapy may hold promise reducing ebv activity cns thereby limiting cns inflammation ms symptoms possibly reversing disease approaches targeting hhv6 hervw limiting inflammatory kinasesignaling treat ms also tested promising results article presents overview evidence ebv hhv6 hervw may pathogenic role initiating promoting ms possible approaches mitigate development diseasepmid34790199 pmcpmc8592026 doi103389 fimmu2021757302,1.0
aqp4iggseronegative patient outcomes nmomentum trial inebilizumab neuromyelitis optica spectrum disorder abstractbackgroundthe nmomentum trial doubleblind randomized placebocontrolled phase 2 3 study inebilizumab neuromyelitis optica spectrum disorder nmosd enrolled participants aquaporin4immunoglobulin g aqp4igg seropositive aqp4+ seronegative aqp4 manuscript reports aqp4 participant outcomesmethodsaqp4igg serostatus determined screened participants central laboratory using validated fluorescenceobservation cellbinding assay medical histories screening data aqp4 participants assessed independently eligibility committee three clinical experts screening diagnosis nmosd confirmed majority decision using 2006 neuromyelitis optica criteria myelin oligodendrocyte glycoproteinimmunoglobulin g mogigg serology using clinically validated flow cytometry assay annualized attack rates aars evaluated post hoc efficacy outcomes assessed comparing prestudy onstudy aars treated participantsresultsonly 18 50 aqp4 screened participants 36 initially considered eligible randomization 16 randomized received full treatment 4 placebo 1 mogiggseropositive mog+ 12 inebilizumab 6 mog+ common reason failure pass screening among prospective aqp4 participants failure fulfill 2006 nmo mri criteria inebilizumabtreated aqp4 participants onstudy aars 95 confidence interval ci calculated treatment initiation whether randomization received start openlabel period end study lower prestudy rates aqp4 participants n16 mean 95 ci aar 0048 002015 versus 170 074266 respectively subset aqp4 mog+ participants n7 aar 0043 00060302 treatment versus 193 110314 study subset aqp4 mog participants n9 posttreatment aar 0051 00130204 versus 160 102238 three attacks occurred randomized controlled period aqp4 inebilizumab group mild severity attacks occurred aqp4 placebo group low number participants receiving placebo n4 confounds direct comparison inebilizumab group attacks seen aqp4 participant second infusion inebilizumab inebilizumab generally well tolerated aqp4 participants adverse event profile observed similar aqp4+ participantsconclusionthe high rate rejection aqp4 participants enrollment study highlights challenges implementing diagnostic criteria aqp4 nmosd apparent reduction aar participants aqp4 nmosd received inebilizumab warrants investigation,1.0
multiple sclerosis meets systems immunology authors reply correspondence reinhard hohlfeld rightly points major gaps knowledge complex pathophysiology multiple sclerosis topics raised covered review1 limited available space focus cellular immune interactions influencing new bouts inflammatory activity emerge patients established disease rather upstream mechanisms involved disease causation eg early geneenvironment interactions targets presumed downstream consequences eg progressive disease distinguish immune mechanisms involved disease propagation hence therapeutic targets limiting disease activity need mechanisms involved disease initiation2bouts new disease activity patients multiple sclerosis arise interacting immune checks balances potentially shaped myriad internal external factors combine produce state insufficient regulation tissuedirected effectors relative contributions check balance almost certainly differ across individuals example patient can autoimmune disease activity despite relatively normal tcell responses bcell myeloid cell responses sufficiently imbalanced agree fully emphasis complexities contribute biological heterogeneity promise challenges posed systems immunology3 applied precision medicinea major advance precision immunology ability measure individuals immune stateincluding capacity define distinguish normal immune health immune illhealththereby identifying predominant immune imbalances tailored treatment agree yet able translate multiparametric ie multiomic analyses refine individual patient care one major impediment hinges gaps understanding functional consequences given complex omic landscape4 attractive approach require detailed knowledge disease mechanisms create iterative maps integrate landscapes thousands patients known diagnoses outcomes researchers identify clusters omic characteristics associate particular immune states treatment responses eventually enabling clinicians assess new patient fit map therefore likely respond given treatmentthe complex cellular interactions playing health disease humans readily recapitulated animal models need elucidated one potential source insight immune heterogeneity involves measuring immune responses standardised immune perturbations immune therapy immunisation done context sarscov2 mrna vaccination patients multiple sclerosis given anticd20 bcelldepleting therapy5 approach heterogeneity responses vaccine used characterise immune response propensity individual provide novel insights complex vivo interactions immune cell subsets involved maintenance restoration normal immune checks balancesabo reports grants personal fees biogen idec genentechroche merckemd serono novartis personal fees glaxosmithkline medimmune bristolmyers squibbcelgenereceptos sanofigenzyme atara biotherapeutics janssenactelion accure gossamer rl declares competing interests,0.0
comparison dimethyl fumarate vs fingolimod rituximab vs natalizumab treatment multiple sclerosis jama netw open 2021 nov 1 4 11 e2134627 doi 101001 jamanetworkopen202134627abstractimportance diseasemodifying treatment options multiple sclerosis increase comparisons options based realworld evidence may guide clinical decisionmakingobjective compare relapse outcomes 2 pairs diseasemodifying treatments dimethyl fumarate vs fingolimod natalizumab vs rituximabdesign setting participants comparative effectiveness study integrated data clinicbased multiple sclerosis research registry linked electronic health records ehr system january 1 2006 december 31 2016 built treatment groups pairwise diseasemodifying treatment comparison according registry records electronic prescriptions parallel analyses conducted october 11 2019 july 7 2021main outcomes measures main outcomes 1year 2year relapse rates well time relapse compare relapse outcomes study adjusted covariates 2 sources registry ehr corrected confounding biases among covariates doubly robust estimationresults study included 4 treatment groups dimethyl fumarate n 260 198 women 762 227 nonhispanic white individuals 873 mean sd age diagnosis 417 104 years fingolimod n 267 190 women 712 222 nonhispanic white individuals 831 mean sd age diagnosis 379 99 years natalizumab n 204 160 women 784 172 nonhispanic white individuals 843 mean sd age diagnosis 372 106 years rituximab n 115 83 women 722 99 nonhispanic white individuals 861 mean sd age diagnosis 441 111 years significant differences found relapse outcomes dimethyl fumarate fingolimod correcting confounding biases multiple testing difference 1year relapse rate 0028 95 ci 0031 0084 difference 2year relapse rate 0071 95 ci 00080128 relative risk 2year nonrelapse 0957 95 ci 08841035 dimethyl fumarate reference compared rituximab natalizumab associated higher relapse rate 3 outcomes bias correction multiple testing difference 1year relapse rate 0080 95 ci 00130137 difference 2year relapse rate 0132 95 ci 00430189 relative risk 2year nonrelapse 0903 95 ci 08220944 confounders identified ehr data recorded registry data datadriven feature selectionconclusions relevance study reports realworld evidence equivalent relapse outcomes dimethyl fumarate fingolimod relapse reduction favor rituximab relative natalizumab approach illustrates value incorporating ehr data highdimensional covariates realworld treatment comparisonpmid34783826 doi101001 jamanetworkopen202134627,0.0
effectiveness longterm homebased aerobic exercise intervention slowing progression parkinson disease design cyclical lower extremity exercise parkinson disease ii cycleii study phys ther 2021 aug 6pzab191 doi 101093 ptj pzab191 online ahead printabstractobjective relatively short duration studies demonstrated highintensity aerobic exercise improves aspects motor nonmotor function people parkinson disease pwpd however effectiveness longterm exercise intervention slowing disease progression unknown primary aim study determine diseasealtering effects highintensity aerobic exercise administered upright stationary cycle progression pd secondary aim develop prognostic model 12month changes movement disorder society unified parkinsons disease rating scale mdsupdrs iii scores people undergoing aerobic exercise interventionmethods pragmatic multisite singlerater blinded randomized controlled trial will conducted 2 large urban academic medical centers exercise intervention will administered remotely homes 250 participants mild moderate idiopathic pd will followed 12 months participants will randomized 1 homebased aerobic exercise ae 2 usual customary care ucc people ae arm will asked complete inhome aerobic exercise sessions 60 80 heart rate reserve 3 times per week 12 months utilizing commercially available upright exercise cycle ucc group will continue normal activity levels daily activity will monitored groups throughout 12month study period primary outcome assess diseasemodifying response aerobic exercise prognostic modeling aerobic exercise arm 12month rate change mdsupdrs iii clinical biomechanical measures will also used assess upper lower extremity motor function nonmotor functionsimpact longterm aerobic exercise demonstrates diseasemodifying capabilities study will provide evidence exercise medicine pwpd derived prognostic model will inform patientspecific exercise prescription pwpd inform expected disease progressionpmid34363478 doi101093 ptj pzab191,0.0
assessment treatment depression people multiple sclerosis qualitative analysis specialist clinicians experiences abstractbackgrounddepression common people multiple sclerosis ms lifetime prevalence estimates 2550 depression commonly underdiagnosed undertreated people ms qualitative study assessed current practices well facilitators required resources improve detection management depression people msmethodsms clinicians living australia recruited ms healthcare provider clinics networks online interviews interviews transcribed coded nvivo framework analysisresultsparticipants included 15 ms specialists nine nurses six neurologists participants appreciated depression common symptom ms untreated depression impacted patientsnull wellbeing medication adherence capacity selfcare employment interpersonal relationships participants routinely screen depression noted lack time skills manage depression identified often recommending patients see general practitioner clinicians recognised people ms commonly experience barriers identifying managing depressive symptoms however clinics provide information discussion depression symptom ms patients findings suggest collaborative management depression improvement practices improve outcomesconclusionparticipants indicated need evidencebased guidance education training improve practices including screening depression urgent need local referral pathways affordable accessible mental health services people ms,0.0
multimodal assessment regional gray matter integrity early relapsingremitting multiple sclerosis patients normal cognition voxelbased structural perfusion approach br j radiol 2021 sep 720210308 doi 101259 bjr20210308 online ahead printabstractobjective increasing evidence gray matter gm impairment strongly associated clinical performance decline aim perform voxelwise analysis regional gm rgm perfusion structural abnormalities early relapsingremitting multiple sclerosis patients normal cognition rrmsic explore clinical correlate early rgm abnormalitiesmethods materials studied 14 early rrmsic patients 14 healthy age sexmatched controls brain perfusion single photon emission computed tomography spect structural mri comprehensive neuropsychological examination acquired participants neuropsychological tests include expanded disability status scale minimal mental status examination short physical performance battery wechsler memory scale quick smell test voxelbased morphometry used analyzing spect t1mr images identify rgm hypoperfusion atrophy respectively rrmsic vs controls group analysis also patient vs controls individual analysis p 0001 anatomical location impaired regions acquired automated anatomical labeling softwareresults significant difference total gm volume rrmsic healthy controls however rgm atrophy hypoperfusion detected individual analysis revealed rgm impairment compared group analysis rgm hypoperfusion extensive rather rgm atrophy rrmsic spatial association rgm atrophy rgm hypoperfusion p 005 rgm abnormalities correlated several relevant minimal clinical deficitsconclusion lack spatial correlation rgm atrophy hypoperfusion might suggest independent mechanisms might underlie atrophy hypoperfusion perfusion spect may provide supplementary information along mriadvances knowledge association rgm atrophy rgm hypoperfusion clinical significance early rrmsic well described yet study showed spatial dissociation rgm atrophy rgm hypoperfusion suggesting different mechanisms might underlie pathologiespmid34491820 doi101259 bjr20210308,0.0
identifying factors associated hospital readmission rate among patients major depressive disorder background major depressive disorder mdd common recurrent mental disorder one leading causes disability world recurrence mdd associated increased psychological social burden limitations patient family society therefore action reduce prevent recurrence disorder hospital readmissions depression among patients essentialmethodsthe data retrospective cohort study extracted records 1005 patients mdd hospitalized farshchian hospital hamadan city iran 20112018 hospital readmissions rate due depression episodes modeled using generalized poisson regression gpr demographic clinical characteristics patients considered explanatory variables sas v94 used p 005 resultsa majority patients male 6637 mean standard deviation age onset mdd average number hospital readmissions 3239 1303 years 053 184 respectively patients 743 experience hospital readmissions according results gpr lower age onset disease irr 102 p 0008 illiteracy irr 206 p 0003 living urban areas irr 156 p 0015 history psychiatric illnesses family irr 175 p 0004 history emotional problems irr 142 p 0028 medical disorders irr 144 p 0035 positively associated number hospitalizationsconclusionaccording findings urbanization early onset disease illiteracy family history mental illness emotional problems medical disorders among major risk factors associated increased number hospital readmissions mdd,0.0
acute movement disorders childhood cohort study review literature pediatr emerg care 2021 aug 31 doi 101097 pec0000000000002017 online ahead printabstractobjectives acute movement disorders amd frequent neurological pediatric emergencies studies analyzed amd children none tunisia african country purpose study describe peculiarities amd tunisian pediatric population literature reviewmethods conducted retrospective descriptive study 8 years including 80 children sex ratio 105 mean age onset 48 years amd followed tertiary referral child neurology department north tunisiaresults acute movement disorders mainly hyperkinetic n 67 dystonia n 33 mostly due inherited metabolic diseases imd 11 status epilepticus 10 children chorea n 14 sydenham chorea 5 myoclonus n 14 mostly opsoclonusmyoclonus syndrome 10 tremor n 6 posttraumatic origin half hypokinetic movement disorder md included acute parkinsonism 5 children infectious n 3 postinfectious n 1 malaria posttraumatic origin n 1 mixed md found 8 children mainly due imd half familial lupus two paroxysmal mds seen 2 children one multiple sclerosis one idiopathic origin psychogenic mds found 7 patients mainly dystonic type management amd comprised symptomatic treatment according phenomenology md causative treatment depending etiologyconclusions study illustrated broad range amd children wide spectrum etiologies series described exceptional findings etiologies amd children findings may denote specific profile amd country predominant infectious postinfectious imdpmid34469400 doi101097 pec0000000000002017,0.0
autoantibody screening guillainbarr syndrome background guillainbarr syndrome gbs acute inflammatory neuropathy heterogeneous presentation although evidences support role autoantibodies pathogenesis target antigens remain unknown substantial proportion gbs patients objective study screen autoantibodies targeting peripheral nerve components guillainbarr syndromemethodsautoantibody screening performed serum samples gbs patients included international gbs outcome study 11 different spanish centres screening included testing antiganglioside antibodies antinodo paranodal antibodies immunocytochemistry neuroblastomaderived human motor neurons murine dorsal root ganglia drg neurons immunohistochemistry monkey peripheral nerve sections analysed staining patterns patients controls prognostic value antiganglioside antibodies also analysedresultsnone gbs patients n 100 reacted nodo paranodal proteins tested 61 61 positive least one antiganglioside antibody gbs sera reacted strongly drg neurons frequently controls igg 6 vs 0 p 003 igm 11 vs 22 p 002 immunodetection differences observed proportion patients reacting neuroblastomaderived human motor neurons reactivity monkey nerve tissue frequently detected patients controls specific patterns detected gbs patients igg 13 13 patients reacted strongly schwann cells finally confirmed igg antigm1 antibodies associated poorer outcomes independently known prognostic factorsconclusionour study confirms 1 gbs patients display heterogeneous repertoire autoantibodies targeting nerve cells structures 2 gangliosides frequent antigens gbs patients prognostic value 3 antigendiscovery experiments may elucidate potential antigens gbs,0.0
study covid19 infection following vaccination patients multiple sclerosis abstractbackground time vaccination sarscov2 global priority cases multiple sclerosis ms among first vaccinated populations iran evaluated change frequency covid19 vaccination associated factors severe covid19 infection full vaccinationmethods questionnaire validated investigate basic characteristics age gender education body mass index smoking status comorbidities ms disease treatment status ms type ms duration expanded disability status scale edss disease modifying treatments information covid19 infection severityresults 692 919 participants received doses vaccines sinopharm appeared common type significant difference covid19 infection prevalence seen vaccination full vaccination difference 016 95 ci 012020 p value 0001 difference significant severe cases admitted ward icu relative covid19 cases whole participants basic disease factors edss showed significant association severe covid19 vaccination severe covid19 fully vaccinated cases show significant relation basic disease characteristics except prior history severe allergic reactions 171 p value 0001 discussion decreased frequency infection sarscov2 predictable insignificant difference cases severe forms disease raise concern significant predictor found severe allergic reactions debates anticd20s association severe covid19 vaccine efficacy find significant relation noticeable point found relation edss critical covid19 vaccination absence relation full vaccination,0.0
exposure systemic immunosuppressive ultraviolet radiation alters t cell recirculation sphingosine1phosphate j immunol 2021 sep 24ji2001261 doi 104049 jimmunol2001261 online ahead printabstractsystemic suppression adaptive immune responses major way uv radiation contributes skin cancer development immune suppression also likely explain uv protects autoimmune diseases multiple sclerosis however mechanisms underlying uvmediated systemic immune suppression well understood exposure c57bl 6 mice doses uv known suppress systemic autoimmunity led accumulation cells within skindraining lymph nodes away nonskindraining lymph nodes transfer cd451+ cells nonirradiated donors cd452+ uvirradiated recipients resulted preferential accumulation donor naive t cells decrease activated t cells within skindraining lymph nodes single dose immunesuppressive uv required cause redistribution naive central memory t cells peripheral blood skindraining lymph nodes specifically cd69independent increases sphingosine1phosphate s1p receptor 1negative naive central memory t cells occurred lymph nodes mass spectrometry analysis showed uvmediated activation sphingosine kinase 1 activity resulting increase s1p levels within lymph nodes topical application sphingosine kinase inhibitor skin prior uv irradiation eliminated uvinduced increase lymph node s1p t cell numbers thus exposure immunosuppressive uv disrupts t cell recirculation manipulating s1p pathwaypmid34561229 doi104049 jimmunol2001261,0.0
role tolllike receptors neuroimmune diseases therapeutic targets problems front immunol 2021 nov 1 12777606 doi 103389 fimmu2021777606 ecollection 2021abstracttolllike receptors tlrs class proteins playing key role innate adaptive immune responses tlrs involved development progression neuroimmune diseases via initiating inflammatory responses thus targeting tlrs signaling pathway may considered potential therapy neuroimmune diseases however role tlrs elusive complex neuroimmune diseases addition inadequate immune response tlrs inhibitors experiments recent studies also demonstrated partial activation tlrs conducive production antiinflammatory factors nervous system repair exploring mechanism tlrs neuroimmune diseases combining developing emerging drug may conquer neuroimmune diseases future herein provide overview role tlrs several neuroimmune diseases including multiple sclerosis neuromyelitis optica spectrum disorder guillainbarr syndrome myasthenia gravis emerging difficulties potential solutions clinical application tlrs inhibitors will also discussedpmid34790205 pmcpmc8591135 doi103389 fimmu2021777606,0.0
factors driving delayed time multiple sclerosis diagnosis results populationbased study abstractbackground multiple sclerosis ms highly complex chronic inflammatory disease diagnostic delay reduce available therapeutic options aim identify factors contributing diagnostic delay ms population living municipality biancavillamethods retrospective populationbased study consecutively selected patients ms diagnosed 1992 2018 resident city biancavilla sociodemographic clinical data collected imed database date final ms diagnosis obtained diagnostic delay calculatedresults total 70 patients 667 women found affected ms according 2011 mcdonald criteria municipality biancavilla period 20052010 mean diagnostic delay ms cohort biancavilla 338 56 months median 195 range 1315 multivariate logistic regression confirmed age 40 years lower educational level 15 years motor symptoms onset associated longer diagnostic delayconclusion populationbased study mean delay 30 months occurred initial symptoms ms diagnosis older age onset lower education level motor symptoms onset associated longer ms diagnostic delay,0.0
wearingoff phenomenon ocrelizumab patients multiple sclerosis abstractbackgroundpatients multiple sclerosis ms treated monoclonal antibodies frequently report increase msrelated symptoms prior next dose known wearingoff phenomenon objective study assess prevalence predicting factors wearingoff phenomenon patients ms using ocrelizumabmethodsthis prospective cohort study patients ms receiving ocrelizumab 1 year participants received bcell guided personalized extended interval dosing limit ocrelizumab exposure hospital visits covid19 pandemic cutoff 10 cells l participants completed questionnaires ocrelizumab infusion 2 weeks thereafter demographics clinical radiological characteristics cd19 bcell counts serum neurofilament light snfl levels collected data analyzed using logistic regression analysesresultsseventyone 61 117 participants reported wearingoff phenomenon ocrelizumab treatment frequently reported symptoms fatigue cognitive disability sensory symptoms wearingoff symptoms started 1 week 11 14 weeks 49 4 weeks 37 ocrelizumab infusion fifty participants 43 reported current wearingoff phenomenon first questionnaire higher body mass index threshold bmi 25 increased odds reporting current wearingoff phenomenon 270 95 ci 126 580 p0011 infusion interval edss score mri disease activity clinical relapses cd19 bcell counts snfl levels predictors disappearance wearingoff phenomenon occurred first week ocrelizumab infusion participants participants current wearingoff phenomenon significantly improved selfreported physical psychological functioning ocrelizumab infusion reporting wearingoff phenomenon influence treatment satisfaction forty 109 participants 37 reported postinfusion symptoms fatigue flulike symptoms walking difficulties postinfusion symptoms started directly first week ocrelizumab infusion disappeared within 2 weeksconclusionsthe wearingoff phenomenon reported half patients ms using ocrelizumab bmi identified predicting factor wearingoff phenomenon elicited extending infusion intervals higher bcell counts wearingoff phenomenon ocrelizumab therefore seem reflect suboptimal control ms disease activity,0.0
temporal spatial evolution various functional neurons demyelination induced cuprizone j neurophysiol 2021 oct 20 doi 101152 jn002242021 online ahead printabstractmultiple sclerosis ms inflammatory demyelinating neurodegenerative disease central nervous system cns reported temporal spatial evolution various functional neurons demyelination cuprizone cpz induced mouse model cpz significantly induce damage axons neurons 2 weeks feeding however 46 weeks cpz feeding axons neurons markedly reduced cortex posterior thalamic nuclear group hippocampus simultaneously expression tph+ tryptophan neurons vglut1+ glutamate neurons obviously decreased expression th+ dopaminergic neurons slightly decreased tail part substantia nigra striatum number chat+ cholinergic neurons significantly different brain second week feeding cpz caused higher level glutamate secretion upregulated expression eaat2 astrocytes contribute rapid sufficient glutamate uptake removal finding reveals astrocytedriven glutamate retake protected cns excitotoxicity rapid reuptake glutamate 46 weeks cpz feeding stage although ng2+ oligodendroglia progenitor cells opcs enhanced demyelination foci myelin sheath still absent conclusion comprehensively observed temporal spatial evolution various functional neurons results will assist understanding demyelination affects neurons cpzinduced demyelination provides novel information neuroprotection myelin regeneration demyelinating diseasespmid34669500 doi101152 jn002242021,1.0
new prospects ultrahighfield magnetic resonance imaging multiple sclerosis invest radiol 2021 jun 11 doi 101097 rli0000000000000804 online ahead printabstractthere growing interest imaging multiple sclerosis ms ultrahighfield uhf lens currently means static magnetic field strength 7 t higher higher signaltonoise ratio enhanced susceptibility effects uhf magnetic resonance imaging improves conspicuity ms pathological hallmarks among cortical demyelination central vein sign turn improve confidence ms diagnosis might also facilitate therapeutic monitoring ms patients furthermore uhf imaging offers unique insight ironrelated pathology leptomeningeal inflammation spinal cord pathologies neuroinflammation yet limitations longer scanning times achieve improved resolution incipient safety data implanted medical devices need considered review discuss applications uhf imaging ms advantages limitations practical aspects uhf clinical settingpmid34120128 doi101097 rli0000000000000804,1.0
voluntary cooling exercise augmented people multiple sclerosis experience heat sensitivity med sci sports exerc 2021 may 24 doi 101249 mss0000000000002707 online ahead printabstractintroduction tested hypothesis people multiple sclerosis ms experience heat sensitivity voluntarily engage coolseeking behavior exercise greater extent healthy controlsmethods 270 02 c 41 2 rh environment 7 participants relapsingremitting ms exhibited heat sensitivity 7 healthy controls completed two randomized trials cycling 40 min ex 35 wkg1 metabolic heat production followed 30 min recovery rec one trial participants restricted engaging cooling con participants voluntarily pressed button receive 2 min 2 c water perfusing top cool mean skin core temperatures mean skin wettedness recorded continuously total time cooling provided index coolseeking behavior ratings perceived exertion rpe total symptom scores tss ms subjective fatigue ms recorded every 10 minresults core temperature +05 01 c skin wettedness +053 002 au increased different groups trials endexercise p 0196 endrecovery p 0342 mean skin temperature reduced cool compared con endexercise p 0002 differences groups p 0532 ms spent total time cooling ex ms 13 3 min healthy 7 4 min p 0001 rec ms 2 1 min healthy 0 1 min p 0496 rpe greater endexercise ms p 0001 tss increased exercise p 0005 different trials p 0321 subjective fatigue attenuated cooling trial p 0065 conclusion voluntary cooling augmented ms consistently mitigate perceptions heat related symptoms subjective fatiguepmid34033624 doi101249 mss0000000000002707,0.0
genetic variation ndfip1 modifies metabolic patterns immune cells multiple sclerosis patients sci rep 2021 nov 1 11 1 21371 doi 101038 s41598021005288abstractone 233 polymorphisms associated multiple sclerosis ms susceptibility lies within ndfip1 gene previously identified eqtl healthy controls ndfip1 shows interesting immune functions involved development central nervous system aimed studying ndfip1 variant activation metabolism immune cells ndfip1 mrna protein expression assessed pbmcs qpcr western blot 87 ms patients 84 healthy controls genotyped rs4912622 immune activation pha stimulation evaluated cd69 upregulation metabolic function basal phaactivated lymphocytes studied seahorse xfpanalyzer minorallele homozygous controls patients found higher ndfip1 expression significantly reduced protein levels cd69 upregulation b tcells pbmcs minorallele homozygous controls showed significantly higher basal mitochondrial respiration atp production compared majorallele carriers minorallele homozygous patients showed significantly lower metabolic activity carriers major allele conclusion describe associations minorallele homozygous controls lower levels ndfip1 protein cd69 upregulation raised mitochondrial activity replicated ms patients suggesting ndfip1 differential effect health diseasepmid34725369 doi101038 s41598021005288,0.0
impact brain lesions sexual dysfunction patients multiple sclerosis systematic review magnetic resonance imaging studies abstractbackground sexual dysfunction common underestimated clinical symptom ms patients growing body evidence suggested link brain lesions sexual dysfunction sd patients multiple sclerosis ms however clinical research investigating relationship shown inconsistentresults aimed systematically review magnetic resonance imaging mri studies evaluating association brain lesions sd ms patientsmethods study provided according recommendations preferred reporting items systematic reviews metaanalyses statement comprehensive systematic search online databases performed find eligible studies december 2020 quality studies methodologically assessed using newcastleottawa scale scoreresults identified eight articles regarding ms brain lesions sd search strategy seven studies showed significant associations sd brain lesions three studies investigated brain stem two studies insular occipital region one study frontal lobe prefrontal cortex temporal lobe one study parietal areaconclusion results systematic review showed lesions different brain areas correlated sd ms patients plaques occipital hippocampus areas well left insula appear related dysfunction sexual arousability lubrication erection ms patients orgasmic dysfunction ms patients may associated brain lesions pons left temporal periventricular right occipital areas,0.0
resilience among older adults multiple sclerosis pattern correlates abstractbackground increasing number older adults multiple sclerosis ms present significant challenges associated aging conjunction chronic disabling disease resilience associated healthy aging general population yet limited research resilience correlates among older adults ms current study investigated difference resilience older adults ms demographically matched healthy controls examined associations resilience functional symptomatic sociobehavioral qol outcomes along demographic clinical characteristics among older adults ms method sample included 40 older adults ms 40 sex age matched healthy controls completed measures resilience battery demographic clinical functional symptomatic sociobehavioral qol outcomesresult differences older adults ms healthy controls regarding overall resilience scores resilience subscale scores resilience significantly associated neurological disability depression walking performance selfefficacy purpose lifeconclusion study suggests resilience older adults ms comparable healthy older adults positively associated walking performance selfefficacy purpose life negatively associated depression neurological disability believe time ripe developing delivering interventions among lower resilience improving resilience associated secondary outcomes,0.0
lymphopenia treatment dimethyl fumarate patients multiple sclerosis prevalence predicting factors clinical outcomes abstractbackgroundlymphopenia common side effect treatment dimethyl fumarate dmf patients multiple sclerosis pwms prevalence predictive factors side effect still uncertain literature provided discrepant results still matter debate lymphopenia associated better treatment outcomemethodswe retrospectively recruited pwms treated least one month dmf collected clinical demographic data absolute lymphocyte count alc followup lymphopenia graded according ctcae patients according grade lymphopenia grades severe lymphopenia grade iiiv evaluate predictors lymphopenia compared characteristics patients without lymphopenia patients without severe lymphopenia logistic binary regression performed elucidate predictive factor lymphopenia severe lymphopenia area curve auc calculated evaluate sensibility specificity predictors analyzed treatment outcome neda3 status 1 2yearsresults98 105 patients treated dmf included 46 9 developed lymphopenia 27 6 severe lymphopenia lymphopenia associated basal alc p0001 auc0786 treatment duration p001 auc0685 reduction third month p0001 auc0616 severe lymphopenia associated basal alc p0003 auc0750 neda3 status 1year n66 2year n44 differ patients without lymphopenia p0059 p0583 without severe lymphopenia p102 p0169 conclusionlymphopenia common side effect dmf basal alc predicts development lymphopenia associated achievement neda3 status,0.0
brain areas involved obsessivecompulsive disorder present different dna methylation modulation background obsessivecompulsive disorder ocd characterized intrusive thoughts repetitive actions presents involvement corticostriatal areas contribution environmental risk factors ocd development suggests epigenetic mechanisms may contribute pathophysiology dna methylation changes gene expression evaluated postmortem brain tissues cortical anterior cingulate gyrus orbitofrontal cortex ventral striatum nucleus accumbens caudate nucleus putamen areas eight ocd patients eight matched controlsresultsthere differentially methylated cpg cytosinephosphateguanine sites dmss brain area nevertheless gene modules generated cpg sites proteinproteininteraction ppi showed enriched gene modules brain areas ocd cases controls brain areas nucleus accumbens presented predominantly hypomethylation pattern differentially methylated regions dmrs although common transcriptional factors targeted dmrs targeted differentially expressed genes different among brain areas proteinprotein interaction network based methylation gene expression data reported brain areas enriched gprotein signaling pathway immune response apoptosis synapse biological processes brain area also presented enrichment specific signaling pathways finally ocd patients controls present significant dna methylation age differencesconclusionsdna methylation changes brain areas involved ocd especially involved genes related synaptic plasticity immune system mediate action genetic environmental factors associated ocd,0.0
microglia macrophage exhibit attenuated inflammatory response ferroptosis resistance rsl3 stimulation via increasing nrf2 expression many neurological diseases involve neuroinflammation overproduction cytokines immune cells especially microglia can aggregate neuronal death ferroptosis recently discovered cell met,0.0
facultative human oral pathogen prevotella histicola equine cheek tooth apical#x2f periapical infection case report background prevotella histicola facultative oral pathogen certain conditions causes pathologies caries periodontitis humans prevotella spp also colonize oral cavity horses can cause disease p histicola yet identifiedcase presentationa 12yearold tinker mare referred clinic persistent malodorous purulent nasal discharge quidding conservative antibiotic penicillin antiphlogistic meloxicam mucolytic dembrexinehydrochloride treatment prior referral unsuccessful symptoms worsened oral examination radiography sino rhinoscopy standing computed tomography revealed severe apical periapical infection upper cheek tooth 209 accompanying unilateral sinonasal inflammation conchal necrosis tooth exhibited extensive subocclusal mesial infundibular cemental hypoplasia caries occlusal fissure fracture mechanical debridement thermoplastic resin filling spacious subocclusal carious infundibular lesion tooth extracted intraorally sinusitis conchal necrosis treated transendoscopically selective bacteriological swab cultures affected tooth roots subsequent matrixassisted laser desorption ionizationtime flight mass spectrometry showed infection obligate anaerobic gramnegative bacterium p histicola surgical intervention adapted antibiotic therapy led normal healing without complicationsconclusionsthis study provides first documented case dental infection horse caused p histicola indicating necessity sufficient microbiological diagnostics targeted antibiotic treatment equine dental practice finding also conducive understand speciesspecific prevotella diversity crossspecies distribution,0.0
fty720 induces neutrophil extracellular traps via nadph oxidaseindependent pathway arch biochem biophys 2021 aug 23109015 doi 101016 jabb2021109015 online ahead printabstractfty720 immunosuppressive agent approved treat multiple sclerosis ms main object present study investigate whether fty720 potential induce formation neutrophil extracellular traps nets vitro using sytox green assay fluorescence microscopy results showed fty720 trigged net formation contrast classic net formation induced phorbol 12myristate 13acetate pma fty720induced nets detected earlier independent nadph oxidase nox activity pharmacological inhibitor experiments indicated autophagy also required net formation induced fty720 moreover p38 akt inhibitor significantly suppressed net formation fty720 whereas erk inhibitor effect suggesting fty720induced nets depended activation p38 akt found citrullination histone h3 peptidylarginine deiminase 4 pad4 mediated fty720induced net formation interestingly necroptosis signaling activation involved vital net formation fty720 however plasma membrane rupture resulting necroptosis major component net formation described collectively findings indicated fty720 potential antibacterial drug protect host pathogen infectionpmid34437865 doi101016 jabb2021109015,0.0
tale two nephropathies cooccurring alport syndrome iga nephropathy case report background alport syndrome iga nephropathy igan disorders can cause hematuria alport syndrome commonly xlinked disease caused col4a5 mutation mutations col4a3 col4a4 chromosome two also common causes alport syndrome igan common glomerulonephritis worldwide though igan usually sporadic estimated 15 cases inheritable component cases familal iga nephropathy figan can mutations genes known cause alport syndromecase presentationwe report case 27yearold man strong family history renal disease presented hematuria new nonnephrotic range proteinuria physical exam showed abnormalities creatinine remained persistently elevated renal ultrasound exhibited bilaterally increased echogenicity consistent chronic kidney disease twentyfourhour urinary collection revealed nonnephrotic range proteinuria 14 g otherwise negative workup biopsy iga positive immunofluorescent staining well moderate interstitial fibrosis tubular atrophy electron microscopy showed basketweave pattern thickening splitting lamina densaconsistent alport syndrome well mesangial expansion electrondense deposits consistent iganconclusionsmutations col4a5 x chromosome well mutations col4a3 col4a4 chromosome 2 can cause alport syndrome figan genome wide association studies identified certain angiotensin converting enzyme gene polymorphisms independent risk factors progression igan presentation cooccurring pathology suggests new paradigm alport syndrome figan may represent manifestations single disease spectrum rather two disparate pathologies appreciating hematuria framework implications treatments genetic counseling genome wide association studies will likely increase understanding alport syndrome figan causes hematuria,0.0
evolution multiple sclerosis spain last decade patient#39 s perspective abstractbackground updated information selfreported experience satisfaction care ms patients pwms spain scarce aim describe pwmsnull perspective disease impact quality life satisfaction level social healthcare support spain evolution last decademethods multicentre observational study based crosssectional nationwide survey completed 432 pwms spain throughout 2018 results compared similar study carried 2007 370 patients whose database retrieved baseline informationresults 432 patients recruited 61 neurology units fully completed study esurvey mean age 437 years 714 women personal profile patients largely similar 2007 2018 samples proportion patients identified relapsingremitting ms higher 2018 771 vs 567 2007 p00001 overall 2018 patients considered labouractive less disabled independent movement higher family income earners proportion patients satisfied satisfied healthcare services accessibility increased time 549 2007 vs 662 2018 p00009 similarly patients considered health condition good good 2018 558 vs 337 2007 p00001 contrast seems little progress social support terms opportunities equalityconclusions health condition pwms seems improved last decade result increasingly effective health care however social protection measures needed,0.0
green leafy vegetable lutein intake multiple health outcomes food chem 2021 may 18 360130145 doi 101016 jfoodchem2021130145 online ahead printabstractgreen leafy vegetables glvs key element healthy eating patterns important source lutein clarify evidence associations glvs lutein intake multiple health outcomes performed review total 24 metaanalyses 29 health outcomes identified eligibility criteria doseresponse analyses revealed per 100 g d glv intake associated decreased risk ca 25 allcause mortality coronary heart disease stroke beneficial effects glv intake found cardiovascular disease bladder oral cancer dietary lutein intake inversely associated agerelated macular degeneration agerelated cataracts coronary heart disease stroke oesophageal cancer nonhodgkin lymphoma metabolic syndrome amyotrophic lateral sclerosis caution warranted contamination potentially pathogenic organisms specifically escherichia coli glv consumption lutein intake therein generally safe beneficial multiple health outcomes humanspmid34034049 doi101016 jfoodchem2021130145,0.0
wavelet coherence measure trunk stabilizer muscle activation wheelchair fencers background intermuscular synchronization constitutes one key aspects effective sport performance activities daily living aim study assess synchronization trunk stabilizer muscles wheelchair fencers use wavelet analysismethodsintermuscular synchronization antagonistic emgemg coherence evaluated pairs right left latissimus dorsi external oblique abdominal ld eoa muscles study group consisted 16 wheelchair fencers members polish paralympic team divided two categories disability b data analysis carried three stages 1 muscle activation recording using semg 2 wavelet coherence analysis 3 coherence density analysisresultsin paralympic wheelchair fencers regardless disability category muscles activated low frequency levels 820 hz category fencers 515 hz category b fencersconclusionsthe results demonstrated clear activity trunk muscles wheelchair fencers including spinal cord injury can explained outcome intense training emg signal processing application great potential performance improvement diagnosis wheelchair athletes,0.0
kaposis sarcomaassociated herpesvirus infection promotes proliferation shsy5y cells notch signaling pathway background cancer caused kaposis sarcomaassociated herpesvirus kshv infection one major causes death aids patients patients neurological symptoms appear associated kshv infection based neurotropic tendency virus recent years objectives study investigate effects kshv infection neuronal shsy5y cells identify differentially expressed genesmethodskshv collected islk219 cells realtime pcr used quantify kshv copy numbers kshv used infect shsy5y cells kshv copy number supernatants mrna levels latencyassociated nuclear antigen lana orf26 k81 replication transcriptional activator rta detected realtime pcr proteins detected immunohistochemistry effect kshv infection cell proliferation detected mtt ki67 staining cell migration evaluated transwell wound healing assays cell cycle analyzed flow cytometry expression cdk4 cdk5 cdk6 cyclin d1 p27 measured western blotting levels cell cycle proteins reexamined lanaoverexpressing shsy5y cells transcriptome sequencing used identify differentially expressed genes kshvinfected cells levels notch signaling pathway proteins measured western blotting rna interference used silence notch1 proliferation analyzed againresultsshsy5y cells successfully infected kshv maintained ability produce virions kshvinfected shsy5y expressed lana orf26 k81 rta kshv infection cell proliferation enhanced cell migration suppressed kshv infection accelerated g0 g1 phase cdk4 cdk5 cdk6 cyclin d1 expression increased whereas p27 expression decreased lana overexpression cdk4 cdk6 cyclin d1 expression increased transcriptome sequencing showed 11 258 genes upregulated 1 967 genes downregulated kshvinfected shsy5y notch signaling pathway played role kshv infection shsy5y western blots confirmed notch1 nicd rbpj hes1 expression increased silencing notch1 related proteins cell proliferation ability decreasedconclusionskshv infected shsy5y cells promoted cell proliferation kshv infection increased expression notch signaling pathway proteins may associated enhanced cell proliferation,0.0
phase ii clinical trial repeated intrathecal injections autologous mesenchymal stem cells patients amyotrophic lateral sclerosis front biosci landmark ed 2021 oct 30 26 10 693706 doi 1052586 4980abstractbackground mesenchymal stem cells msc shown induce beneficial effects animal models neurodegeneration pilot human trials multiple sclerosis amyotrophic lateral sclerosis als aim openlabel clinical trial evaluate safety efficacy repeated intrathecal administrations autologousmsc alspatients methods study included 20 subjects age 2070 definite diagnosis als amyotrophic lateral sclerosis functional rating scale revised alsfrsr score 20 patients treated 14 intrathecal injections msc intervals 36 months primary endpoints safety tolerability efficacy measurements including alsfrsr score forced vital capacity fvc assessed secondary endpoints results serious adverse events observed whole period trial one patient withdrew study first injection monthly rate progression alsfrsr ameliorated 25 15 19 patients 1st 2nd injection mean improvement 1071 11 12 2nd 3rd injection 8 10 3rd 4th injection overall whole period till last transplantation 13 patients 25 improvement slope progression alsfrsr mean improvement 474 p 00038 wilcoxon rank signed test 7 19 patients actually improved clinically range increase alsfrsr +1 +4 degrees first transplantation 5 remained improved second cycle response rate correlated timeintervals injections conclusion results study show repeated intrathecal injections autologous msc safe patients als provide indications mediumterm clinical benefits related intervals administrations cells larger studies needed confirm observationspmid34719198 doi1052586 4980,0.0
tcell dysregulation associated disease severity parkinsons disease abstractthe dysregulation peripheral immunity parkinsons disease pd includes changes relative numbers gene expression t cells presence peripheral tcell abnormalities pd welldocumented less known association clinical parameters age age onset progression rate severity disease took detailed look tcell numbers gene expression activation crosssectional cohorts pd patients agematched healthy controls means flow cytometry nanostring gene expression assay show wellpronounced decrease relative tcell numbers pd blood mostly driven decrease cd8+ cytotoxic t cells primarily associated severity disease addition demonstrate expression inflammatory genes t cells pd patients also associated disease severity pd t cells presented increased activation upon stimulation phytohemagglutinin also correlated disease severity summary data suggest consequences disease severity account changes pd t cells rather age age onset duration disease progression rate,0.0
sarscov2 ebv cost second mitochondrial whammy abstractwe others suggested sarscov2 virus may modulate mitochondrial function good mitochondrial reserve health key determining disease severity exposed virus immune system dependent organelles function recent publication paper showing long covid associated reactivation epstein barr virus well known manipulate mitochondria suggest represent second mitochondrial whammy might support mitochondrial hypothesis underlying covid19 severity potentially occurrence longerterm symptoms mitochondrial function declines age important factor older populations susceptible key factors ensure optimal mitochondrial health generally ensure healthy ageing good lifestyle plenty physical activity ability viruses manipulate mitochondrial function well described now also thought evolutionary reasons also manipulate ageing process given slowing ageing process well linked better economic outcomes link mitochondrial health economics covid19 viruses well lifestyle needs considered,0.0
prmt5 promotes symmetric dimethylation rna processing proteins modulates activated t cell alternative splicing ca2+#x2f nfat signaling immunohorizons 2021 oct 29 5 10 884897 doi 104049 immunohorizons2100076abstractprotein arginine methyltransferase prmt 5 type 2 methyltransferase catalyzing symmetric dimethylation arginine prmt5 inhibition deletion cd4 th cells reduces tcr engagementinduced il2 production th cell expansion confers protection experimental autoimmune encephalomyelitis animal model multiple sclerosis however mechanisms prmt5 modulates th cell proliferation still completely understood neither methylation targets t cells manuscript uncover role prmt5 alternative splicing activated mouse t cells identify several targets prmt5 symmetric dimethylation involved splicing addition find possible link prmt5mediated alternative splicing transient receptor potential cation channel subfamily m member 4 trpm4 tcr nfat signaling il2 production understanding may guide development drugs targeting processes benefit patients t cellmediated diseasespmid34716181 doi104049 immunohorizons2100076,0.0
case report portal cavernoma secondary multiple liver hydatidosis rare cause cataclysmic haemorrhage young adult f1000res 2021 oct 29 101097 doi 1012688 f1000research740121 ecollection 2021abstractclinical presentation liver hydatidosis can vary asymptomatic forms lethal complications report rare case 27yearold male rural tunisian region presented largeabundance haematemesis haemodynamic instability marked biological signs hypersplenism endoscopy showed bleeding esophageal varicose veins ligated abdominal ultrasound concluded presence three type ce2 hydatic liver cysts causing portal cavernoma signs portal hypertension despite resuscitation patient died massive rebleeding leading haemorrhagic shock hepatic hydatid cyst considered indirect cause gastrointestinal bleeding endemic countries early abdominal ultrasound varicose haemorrhage essential orienting diagnosispmid34900234 pmcpmc8630548 doi1012688 f1000research740121,0.0
tolllike receptors tolllike receptortargeted immunotherapy glioma abstractglioma represents fast proliferating highly invasive brain tumor resistant current therapies invariably recurs despite advancements antiglioma therapies patients prognosis remains poor tolllike receptors tlrs act first line defense immune system detectors associated bacteria viruses danger signals glioma microenvironment tlrs expressed immune tumor cells playing dual roles eliciting antitumoral innate adaptive immunity protumoral cell proliferation migration invasion glioma stem cell maintenance responses date several tlrtargeting therapies developed aiming glioma bulk stem cells infiltrating immune cells immune checkpoint axis among others tlr agonists exhibited survival benefit clinical trials attracts attention involved combinatorial treatment radiation chemotherapy immune vaccination immune checkpoint inhibition glioma treatment tlr agonists can used immune modulators enhance efficacy treatment avoid dose accumulation brings interests can potentiate immune checkpoint delayed resistance pd1 pdl1 blockade upregulating pd1 pdl1 overexpression thus unleash powerful antitumor responses combined immune checkpoint inhibitors herein focus recent developments clinical trials exploring tlrbased treatment provide picture relationship tlr glioma implications immunotherapy,0.0
role multifocal visually evoked potential biomarker demyelination spontaneous remyelination myelin repair multiple sclerosis front neurosci 2021 oct 29 15725187 doi 103389 fnins2021725187 ecollection 2021abstractmultiple sclerosis ms complex disease central nervous system cns characterized inflammation demyelination neuroaxonal loss gliosis inflammatory demyelinating lesions hallmark disease spontaneous remyelination however often incomplete strategies promote remyelination needed result accurate sensitive vivo measures remyelination necessary visual pathway provides unique opportunity vivo assessment myelin damage repair msaffected brain since highly susceptible damage ms frequent site ms lesions visually evoked potential vep eventrelated potential generated striate cortex response visual stimulation uniquely placed serve biomarker myelination along visual pathway multifocal vep mfvep represents recent addition array vep stimulations article provides current view role mfvep biomarker demyelination spontaneous remyelination myelin repair mspmid34776840 pmcpmc8586643 doi103389 fnins2021725187,1.0
case report persisting lymphopenia neuropsychiatric tumefactive multiple sclerosis rebound upon fingolimod withdrawal front neurol 2021 oct 29 12785180 doi 103389 fneur2021785180 ecollection 2021abstractfingolimod fty disease modifying therapy relapsing remitting multiple sclerosis rrms can lead severe lymphopenia requiring therapy discontinuation order avoid adverse events however can result severe disease reactivation occasionally presenting tumefactive demyelinating lesions tdls tdls thought originate massive reentry activated lymphocytes central nervous system larger 2 cm diameter may feature mass effect perifocal edema gadolinium enhancement cases can challenging exclude important differential diagnoses tdls progressive multifocal leukoencephalopathy pml opportunistic infections present case 26yearold female patient suffered massive rebound tdls following fty discontinuation primarily neuropsychiatric symptoms despite persisting lymphopenia two cycles seven plasmaphereses necessary achieve remission ocrelizumab used longterm stabilizationpmid34777236 pmcpmc8585856 doi103389 fneur2021785180,1.0
treatment multiple sclerosis teriflunomide multicenter study real clinical practice valencian communityspain front neurol 2021 oct 29 12727586 doi 103389 fneur2021727586 ecollection 2021abstractintroduction different treatment alternatives relapsingremitting multiple sclerosisrrmswithin socalled platform drugs desirable know ideal drug patient real clinical practice studies provide us data drug efficacy medium long term safety beyond clinical trials can help us know patient profile appropriate therapy material methods observational multicenter study real clinical practice patients rrms treated teriflunomide valencian community since teriflunomide authorized spain database created study collects retrospectively patients followed prospectively ms clinics objectives analyze efficacy safety teriflunomide treatment patients rrms conditions real clinical practice identify patient profile responding treatment results obtained data 340 patients received least one dose 14 mg teriflunomide patients 694 female 306 male mean age 464 years mean time progression ms 115 years mean preteriflunomide relapse rate 04 years mean edss scorewas 198 igg oligoclonal bands present csf 662 patients igm oligoclonal bands present 469 mean number gadoliniumenhancing lesions 107 lesions per patient beginning treatment average number treatments previously received 104 2853 nave followup 4 years reduction annualized cumulative annualized relapse rate observed first year second year third year compared pretreatment year edss scores stabilized throughout followup likewise reduction gadoliniumenhancing lesions 1st 2nd years compared pretreatment period applying different generalized multiple linear regression models identified profile responding patient teriflunomide male without igm oligoclonal bands csf previous edss score 3 5 years duration mspmid34803877 pmcpmc8603659 doi103389 fneur2021727586,1.0
higher burden multiple sclerosis genetic risk confers earlier onset abstractbackgroundage onset multiple sclerosis ms objective influential predictor evolution ms independent disease durationobjectivesdetermine influence ms genetic predisposition age onsetmethodswe conducted comprehensive investigation ms risk variants age onset 3495 nonlatinx white individuals including combinations hladrb11501 alleles quintiles unweighted genetic risk score grs 198 200 autosomal ms risk variants reside outside major histocompatibility complexresultsthe mean age onset 32years 29 male 46 hladrb11501 carriers greatest genetic risk burden highest grs quintile two hladrb11501 alleles average 5years younger onset p0002 lowest genetic risk burden lowest grs quintile hladrb11501 alleles strong inverse relationship ms genetic risk burden age onset ms p5108 conclusionwe demonstrate significant gradient elevated ms genetic risk burden earlier onset ms suggesting higher ms genetic risk burden accelerates onset disease,0.0
cd8+ t cells specific cryptic apoptosisassociated epitopes exacerbate experimental autoimmune encephalomyelitis cell death dis 2021 oct 29 12 11 1026 doi 101038 s41419021043106abstractthe autoimmune immunopathology occurring multiple sclerosis ms sustained myelinspecific nonspecific cd8+ t cells previously shown ms activated t cells undergoing apoptosis induce cd8+ t cell response directed antigens unveiled apoptotic process namely caspasecleaved structural proteins nonmuscle myosin vimentin explored vivo development function immune responses cryptic apoptosisassociated epitopes aes wellestablished mouse model ms experimental autoimmune encephalomyelitis eae combination immunization approaches multiparametric flow cytometry functional assays first confirmed model recapitulated main findings observed ms patients namely apoptotic t cells effector memory aespecific cd8+ t cells accumulate central nervous system mice eae positively correlating disease severity interestingly found aespecific cd8+ t cells present also lymphoid organs unprimed mice proliferated peptide stimulation vitro failed respond peptide immunization vivo suggesting physiological control response however mice immunized aes along eae induction aespecific cd8+ t cells effector memory phenotype accumulated central nervous system disease severity exacerbated conclusion demonstrate aespecific autoimmunity may contribute immunopathology neuroinflammationpmid34716313 doi101038 s41419021043106,1.0
integrins regulate stemness solid tumor emerging therapeutic target abstractintegrins adhesion molecules transmembrane receptors consist subunits binding extracellular matrix components integrins trigger intracellular signaling regulate wide spectrum cellular functions including cell survival proliferation differentiation migration since pattern integrins expression key determinant cell behavior response microenvironmental cues deregulation integrins caused various mechanisms causally linked cancer development progression several solid tumor types review discuss integrin signalosome highlight key prooncogenic pathways elicited integrins uncover mutational transcriptomic landscape integrinencoding genes across human cancers addition focus integrinmediated control cancer stem cell tumor stemness general tumor initiation epithelial plasticity organotropic metastasis drug resistance insights integrins contribute stemlike functions now gain better understanding integrin signalosome will greatly assist novel therapeutic development precise clinical decisions,0.0
factors influencing failure undergo interval cholecystectomy percutaneous cholecystostomy among patients acute cholecystitis retrospective study background percutaneous cholecystostomy pc interval cholecystectomy effective treatment modality highrisk patients acute cholecystitis however patients still fail undergo interval cholecystectomy pc reasons rarely reported hence study aimed explore factors prevent patient undergoing interval cholecystectomymethodsdata patients acute cholecystitis undergone pc january 1 2017 december 31 2019 hospital retrospectively collected followup endpoint patient undergoing cholecystectomy patients failed undergo cholecystectomy followed every three months death univariate multivariate analyses performed analyze factors influencing failure undergo interval cholecystectomy nomogram used predict numerical probability noninterval cholecystectomyresultsoverall 205 participants identified 67 327 undergo cholecystectomy followup period multivariate analysis revealed tokyo guidelines 2018 tg18 grade iii status odds ratio 383 95 confidence interval ci 1271149 p 0017 acalculous cholecystitis 455 95 ci 1591250 p 0005 albumin level 28 g l 415 95 ci 1091581 p 0037 history malignancy 465 95 ci 1621337 p 0004 independent risk factors patients failure undergo interval cholecystectomy among presence history malignancy exhibited highest influence nomogram predicting noninterval cholecystectomyconclusionshaving tg18 grade iii status acalculous cholecystitis severe hypoproteinemia history malignancy influence failure undergo cholecystectomy pc patients acute cholecystitis,0.0
influencing factors complication aneurysm rupture fetal posterior communicating artery clipping lateral supraorbital approach prognosis background explore influencing factors complication aneurysm rupture fetal posterior communicating artery clipping lateral supraorbital lso approach prognosismethodsa total 119 patients posterior communicating artery aneurysm pcoaa accompanied fetal posterior cerebral artery fpca underwent clipping lso approach january 2014 december 2019 selected aged 5070 years old 605 137 average treatment outcome incidence complications followup results analyzed based followup results univariate comparative analysis conducted clinical data patients good poor prognosis statistically significant factors incorporated multivariate cox regression analysis nomogram prediction model prognosis established accuracy model assessed using hosmerlemeshow goodnessoffit testresultsclipping lso approach successful cases perioperative complications occurred 41 patients according followup results 89 patients good prognosis 30 poor prognosis age 65 years old history hypertension high hunthess grade high modified fisher grade independent risk factors poor prognosis patients pcoaa accompanied fpca clipping lso approach results obtained established model consistent actual onesconclusionage history hypertension hunthess grade modified fisher grade independent risk factors prognosis patients pcoaa accompanied fpca clipping lso approach,0.0
centrality drug targets protein networks background pharmaceutical industry competing validated drug targets drive identify new ways therapeutic intervention attempted define guidelines evaluate targets fitness based node characteristics within annotated protein functional networks complement contingent therapeutic hypothesesresultswe observed targets approved selective small molecule drugs exhibit high node centrality within protein networks relative broader set investigational targets spanning various development stages targets approved drugs also exhibit higher centrality proteins within respective functional class findings expand previous reports drug targets network centrality suggesting centrality metrics low topological coefficient inherent characteristics good target relative exploratory targets regardless functional class centrality metrics thus indicators individual proteins fitness potential drug target correlations protein nodes network centrality number associated publications underscored possibility knowledge bias inherent limitation predictionsconclusionsdespite entanglement knowledge bias like structureoriented druggability assessments new protein targets centrality metrics assist early pharmaceutical discovery teams evaluating potential targets limited experimental proof concept help allocate resources effective drug discovery pipeline,0.0
atypical involvement central nervous system classic hodgkin lymphoma case report background hodgkin lymphoma systemic disease commonly involves cervical supraclavicular mediastinal lymph nodes involvement central nervous system hodgkin lymphoma extremely rare diagnosis usually established using distinct morphological immunohistochemical staining tissue biopsied extranodal presentation hl rare occurrence evident prognosis encouraging patients disease limited just central nervous system initially relapse compared involvement multiple sites relapsecase presentationwe herein report case 35yearold southeast asian male relapsed hodgkin lymphoma patient developed parotid gland lesion cervical lymphadenopathy significant weight loss intermittent night sweats along spread central nervous system high suspicion tuberculosis upon biopsy cervical lymph node patient confirmed hodgkin lymphoma immediate treatment began six cycles chemotherapy consisting adriamycin bleomycin vinblastine dacarbazine patient received three cycles chemotherapy consisting ifosfamide carboplatin etoposide lost followup five years later patient suffered road traffic accident upon workup right parietal spaceoccupying lesion moderate cerebral edema midline shift found computed tomography brain patient underwent resection spaceoccupying lesion brain features consistent classical hodgkin lymphoma histopathology examination crucial lesions investigated meticulously rule secondary disease processconclusionrelapsed hodgkin lymphoma central nervous system involvement relatively rare just two dozen cases reported date observed infrequently developing nations therefore spaceoccupying lesion always investigated biopsy lesions gold standard establish diagnosis timely appropriate therapy complete remission can achieved however largescale studies prudent explore presentation survival treatment options patients hodgkin lymphoma involving central nervous system,0.0
dysregulation mir638 diabetic nephropathy role inflammatory response background microrna mirna can used biomarker early diagnosis diabetic nephropathy dn purpose study evaluate diagnostic value mir638 dn analyse regulatory effect inflammationmethodsthis retrospective study involved 98 subjects including nondiabetic healthy controls n 30 patients type 2 diabetes t2dm n 36 without complications patients dn n 32 anthropometric biochemical evaluation serum mir638 levels assessed realtime reverse transcriptionpolymerase chain reaction qrtpcr levels inflammatory cytokines interleukin il 1 il6 tumor necrosis factoralpha tnf detected using enzymelinked immunosorbent assay spearman correlations used analyze correlation mir638 urinary albumin excretion uae estimated glomerular filtration rate egfr inflammatory factors furthermore receiver operating characteristic roc curve used measure diagnostic value mir638 dn human mesangial cells hmcs treated normal glucose ng 55 mm glucose high glucose hg 30 mm glucose high osmotic pressure solution ho 55 mm glucose + 245 mm mannitol vitro simulate hyperglycamic state vivo subsequently hmcs transfected mir638 mimics regulate level mir638 cells detect regulation cell inflammation proliferationresultscompared healthy controls patients t2dm serum mir638 patients dn significantly lower reduced mir638 expression significant diagnostic value can significantly distinguish patients dn healthy controls patients t2dm inflammatory factors significantly upregulated patients dn negatively correlated mir638 levels addition mir638 negatively correlated uae positively correlated egfr hg decreased level mir638 promoted expression inflammatory factors proliferation hmcs however mir638 mimic significantly decreased levels inflammatory factors inhibited proliferative ability induced hgconclusionsserum mir638 expression low dn can potentially valuable biomarker dn mirna seems influence inflammatory responses participate progression dn regulating proliferation,0.0
motor improvements enabled spinal cord stimulation combined physical training spinal cord injury review experimental evidence animals humans abstractelectrical spinal cord stimulation scs gaining momentum potential therapy motor paralysis consequence spinal cord injury sci specifically recent studies combining scs activitybased training reported unprecedented improvements motor function people chronic sci persist even without stimulation work first provide overview critical scientific advancements led current uses scs neurorehabilitation eg understanding scs activates dormant spinal circuits lesion recruiting largetomedium diameter sensory afferents within posterior roots discuss led standardization implant position resulted consistent observations independent clinical studies scs combination physical training promotes improvements motor performance neurorecovery reported participants able move previously paralyzed limbs day 1 recovery complex motor functions gradual timeframe first observations proportional task complexity interestingly individuals sci classified ais b c regained motor function paralyzed joints even without stimulation individuals motor sensory complete sci ais experiments animal models sci investigating potential mechanisms underpinning neurorecovery suggest synaptic reorganization corticoreticulospinal circuits correlate improvements voluntary motor control future experiments humans animal models paralysis will critical understand potential limits functional improvements people different types levels timeframes severities sci,1.0
isolated central nervous system familial hemophagocytic lymphohistiocytosis fhlh presenting mimic demyelination children abstractisolated central nervous system cns presentations haemophagocytic lymphohistiocytosis hlh traditionally systemic inflammatory condition reported adults children identified nine patients diagnosis isolated cns familial hemophagocytic lymphohistiocytosis fhlh symptom onset 18years age one asymptomatic sibling children atypical chronic recurrent cns inflammation considered immunological genetic panel testing fhlh even absence systemic inflammatory features despite haematopoietic stem cell transplantation hsct mainstay treatment treatment failure high morbidity mortality posthsct suggest alternative immune therapies may worth considering,1.0
dynamics predictors cognitive impairment along disease course multiple sclerosis j pers med 2021 oct 28 11 11 1107 doi 103390 jpm11111107abstract 1 background evolution predictors cognitive impairment ci multiple sclerosis ms poorly understood aimed define temporal dynamics cognition throughout disease course identify clinical neuroimaging measures predict ci 2 methods paper features longitudinal study 212 patients underwent several cognitive examinations different time points dynamics cognition assessed using mixedeffects linear spline models machine learning techniques used identify baseline demographic clinical neuroimaging measures best predicted ci 3 results first 5 years ms detected increase zscores global cognition verbal memory information processing speed followed decline global cognition memory p 005 years 5 15 15 30 years disease onset cognitive decline continued affecting global cognition verbal memory baseline measures best predicted ci education disease severity lesion burden hippocampus anterior cingulate cortex volume 4 conclusions ms cognition deteriorates 5 years disease onset declining steadily next 25 years markedly affecting verbal memory education disease severity lesion burden volume limbic structures predict future ci may helpful identifying atrisk patientspmid34834459 doi103390 jpm11111107,0.0
clinicopathological characteristics prognosis patients iga nephropathy renal vasculitic lesions background studied patients iga nephropathy igan compared without renal vasculitic lesions rvls methodsfrom january 2006 december 2011 patients biopsyproven primary igan institution retrospectively examined assigned rvl group norvl group rvls defined thromboses arteries arterioles necrosis capillary loops crescent formation fibrinoid necrosis small blood vessels association rvls clinical outcomes analyzed using multivariate models primary composite endpoint endstage renal disease doubling serum creatinineresultsthere 1570 patients 502 788 rvls 498 782 without rvls rvl group younger shorter disease course severe proteinuria hematuria worse renal function prescribed steroids immunosuppressants rvl group greater prevalence global glomerular sclerosis crescents higher oxford classification grade total 501 patients rvl group 507 487 norvl group 493 completed followup rvl group likely reach composite endpoint 1 3 5 years p 0001 proteinuria anemia low egfr global segmental sclerosis independent predictors progression composite endpoint patients rvlsconclusionsalmost half igan patients rvls patients younger worse renal function severe proteinuria hematuria severe pathologic lesions igan patients rvls worse renal outcomes without rvls,0.0
transcriptomic analysis loss gli1 neural stem cells responding demyelination mouse brain sci data 2021 oct 28 8 1 278 doi 101038 s4159702101063xabstractin adult mammalian brain gli1 expressing neural stem cells reside subventricular zone progeny recruited sites demyelination white matter generate new oligodendrocytes myelin forming cells remarkably genetic loss pharmacologic inhibition gli1 enhances efficacy remyelination neural stem cells understand molecular mechanisms involved performed transcriptomic analysis gli1pool neural stem cells compared murine nscs either intact deficient gli1 expression adult mice control diet cuprizone diet induces widespread demyelination data will valuable resource identifying therapeutic targets enhancing remyelination demyelinating diseases like multiple sclerosispmid34711861 doi101038 s4159702101063x,1.0
natural history comparison sod1mutant patients amyotrophic lateral sclerosis chinese german populations currently effective treatment amyotrophic lateral sclerosis als despite limited efficacy riluzole 1 edaravone 2 sod1 coding cu zn superoxide dismutase second frequent genetic cause als c9orf72 patients european ancestry frequent asian als populations 3 multiple therapeutic approaches targeted sod1related als including antisense oligonucleotide tofersen promising results recent phase ii trial 4 given clinical heterogeneity among different sod1 mutations study enrolled genetically confirmed als patients sod1 mutations two prospectively established hospitalbased cohorts china 5 germany 6 clinically characterize distinct sod1 mutations compare related phenotypes asians caucasians explorative nature study results interpreted hypothesisgenerating rather confirmatory adjustment multiple testing madewe identified 66 chinese 84 german als patients carrying total 69 distinct sod1 mutations including 61 known mutations sod1 5 variants uncertain significance 3 likely pathogenic variants frequent mutation populations phis47arg 8 chinese 2 german common mutations featured consistent phenotypes including aggressive form als pgly148asp slowprogressing forms pglu41gly phis47arg pasn87ser additional file 1 table s1 interestingly majority mutations chinese patients located exon 2 german patients exon 4 significant difference average age onset chinese german patients carrying mutations exon 4 374 vs 499 years p0001 site onset diagnostic delay survival differ significantly among exons additional file 1 fig s1 among patients sod1 mutations median interquartile range iqr age onset 460 400540 years chinese patients younger age onset 430 383500 vs 500 410580 p0002 consistent previous study 6 however difference significant adjusting demographic structures identical general als populations 6 p007 proportion youngonset als defined onset 25 45 years 475 two cohorts higher china 625 vs 307 p0001 median iqr body mass index bmi diagnosis significantly lower chinese cohort 226 209249 german cohort 259 231287 p0001 difference remained significant p003 adjusting bmi identical general als populations median bmi 230 chinese 245 german 6 median iqr diagnostic delay 120 60350 months chinese 145 60365 vs german 110 60320 p059 survival 1410 2103640 months chinese available due 60 censored cases german 1980 2203640 p090 despite lower riluzole prescription rate chinese population 283 vs 813 p0001 survival differences observed p090 table 1 table 1 clinical characteristics chinese german als patients sod1 mutationsfull size tablethe majority cases 943 spinal onset difference proportion site onset two groups males females twenty percent patients pure lower motor neuron phenotype chinese 173 german 250 p041 table 1 patients progressed slowly phis47arg others showed aggressive pattern pala5val phis44arg male patients significantly shorter diagnostic delay p001 survival p0005 compared females additional file 1 table s2 fig s2 significant relationship diagnostic delay early late progression rate see definition additional file 2 supplementary methods sex age onset site onset late progression rate included multivariate cox regression analysis revealed patients bulbar onset hazard risk 1031 p001 higher late progression rate hazard risk 242 p0003 much shorter survival time additional file 1 table s3 fig s3 present study three major implications first study reported first time distinct distributions sod1 mutations chinese mainly exon 2 german patients mainly exon 4 consistent phenotypes common mutations common sod1 mutations germany parg116gly 26 patients pasp91ala 11 explained known founder effects among caucasian populations similar effect may involved chinese patients carrying phis47arg 8 patients predominate mutation north america pala5val 7 rare china 1 patient albeit without founder haplotype 8 absent germany second chinese sod1mutant patients significantly lower age onset higher proportion youngonset cases compared german counterparts may reflect higher burden genetic environmental risk factors 9 third known prognostic factors bmi age onset sporadic als associated survival sod1carrying patients indicating different spectrum diseasemodifying factorsin future desirable establish detailed genotypephenotype database sod1 mutationcarriers different populations order clarify underlying pathomechanisms precisely design clinical trials sod1related als,0.0
teriflunomide levels women whose male sexual partner teriflunomide relapsing multiple sclerosis abstractbackgroundfor small molecules teriflunomide used treat relapsing multiple sclerosis ms potentially embryotoxic theoretical risk transmission medication males drug female sexual partners however risk undefined nowmethodsteriflunomide concentrations assayed concomitantly ten sexually active couples using barrier methods contraception male partner ms treatment teriflunomide 14 mg daily least two months results compared male female age teriflunomide concentrations reported average number incidences sexual intercourse per month threshold level detection teriflunomide 0020 g ml femalesresultsthe average age cohort 4670 males 4710 females four ten females detectible teriflunomide concentrations mean 0046g ml range 0220077 standard deviation 0025 male age female teriflunomide positive threshold female teriflunomide concentration inversely correlated r067 r2045 p0034 former r062 r2039 p05 ns latter significant correlations observed female age male teriflunomide concentrations reported mean monthly episodes sexual intercourseconclusionthis limited study suggests small risk low levels teriflunomide can transmitted male female partners via sexual intercourse related male age supports recommendations found united states product insert uspi stating men taking teriflunomide wish father child female partners use reliable contraception men wishing father child discontinue use teriflunomide undergo accelerated elimination procedure reduce plasma concentrations medication less 002 mg l 002 g ml1,0.0
zootherapeutic uses animals excreta case elephant dung urine use sayaboury province laos background despite widespread aversion towards faeces urine animal excreta used traditional medicine many countries since centuries records scattered therapeutic uses accurately documented current context emerging zoonoses records may major interestmethodologyin study investigated therapeutic uses mahouts xayaboury province lao pdr make elephant urine faeces well brood chamber beetles heliocopris dominus fashion elephant dung semistructured interviews conducted mahouts elephant diet health problems responses disease andwhether use elephant products data supplemented interviews traditional healersresultsseven respondents reported use elephant urine ethnoveterinary care elephants human medicine case diabetes otitis 25 respondents reported therapeutic use elephant faeces ef elephant dung beetle brood chambers major indications gastrointestinal skin problems macerations decoctions drunk used externally lotion mahouts attribute therapeutic effectiveness efs content includes remains many species elephant diet consider medicinaldiscussionthe indications uses consistent pharmacological clinical studies highlighting properties different animals urine faeces curative potential tested vivo acknowledgement mahouts medicinal properties elephant faecal bolus contrasts rare justifications animal material use recorded zootherapeutic studies falls within symbolic domain however numerous studies highlight preponderant role microbiota physiological processes raising hypothesis curative action ef rebalancing users microbiotaconclusionthe therapeutic uses ef preparations despite possible curative properties potential source zoonotic transmission elephants humans current context globalisation trade favours emergence zoonoses relation issue one health becomes crucial document zootherapeutic practices prevent emerging diseases elephants local related ethnoethological knowledge threatened documenting urgent contribute preservation,0.0
quality life surveillant endocannabinoid system front neurosci 2021 oct 28 15747229 doi 103389 fnins2021747229 ecollection 2021abstractthe endocannabinoid system ecs important brain modulatory network ecs regulates brain homeostasis throughout development progenitor fate decision neuro gliogenesis synaptogenesis brain plasticity circuit repair learning memory fear protection death major player hypothalamicperipheral systemadipose tissue regulation food intake energy storage nutritional status adipose tissue mass consequently affecting obesity loss ecs control might affect mood disorders anxiety hyperactivity psychosis depression lead drug abuse impact neurodegenerative alzheimers parkinson huntington multiple amyotrophic lateral sclerosis neurodevelopmental autism spectrum disorders practice regular physical mindbody mindfulness meditative activities shown modulate endocannabinoid ecb levels addition players brainderived neurotrophic factor bdnf ecs involved pain inflammation metabolic cardiovascular dysfunctions general immune responses asthma allergy arthritis tumor expansion either brain periphery reason vast impact fact arachidonic acid precursor ecbs present every membrane cell body demand ecbs synthesis regulated electrical activity calcium shifts novel lipid lipoxins resolvins peptide hemopressin players ecs also operate regulators physiological allostasis indeed presence cannabinoid receptors intracellular organelles mitochondria lysosomes nuclear targets ppar might impact energy consumption metabolism cell death live better life implies vigilant ecs healthy diet selection based balanced omega3 6 polyunsaturated fatty acids weekly exercises meditation therapy regulating ecbs levels surrounded constructive social network cannabidiol diet supplement major player antiinflammatory anxiolytic antidepressant antioxidant activities cognitive challenges emotional intelligence might strengthen ecs built variety synapses modify human behavior therapeutically concerned ecs essential maintaining homeostasis cannabinoids promising tools control innumerous targetspmid34776851 pmcpmc8581450 doi103389 fnins2021747229,0.0
vivo highresolution structural mribased atlas human thalamic nuclei sci data 2021 oct 28 8 1 275 doi 101038 s4159702101062yabstractthalamic nuclei play critical roles regulation neurological functions like sleep wakefulness increasingly implicated neurodegenerative neurological diseases multiple sclerosis essential tremor however segmentation thalamic nuclei difficult due poor visibility conventional mri scans sophisticated methods proposed require specialized mri acquisitions complex post processing high spatial resolution 1 mm3 higher vivo mri thalamic atlases available currently goal work development vivo mribased structural thalamic atlas 07 07 05 mm resolution based manual segmentation 9 healthy subjects using morel atlas guide using data analysis healthy subjects well patients multiplesclerosis essential tremor 3t 7t mri demonstrate utility atlas provide fast accurate segmentation thalamic nuclei conventional t1 weighted images availablepmid34711852 doi101038 s4159702101062y,0.0
immune regulatory cell bias following alemtuzumab treatment relapsingremitting multiple sclerosis front immunol 2021 oct 28 12706278 doi 103389 fimmu2021706278 ecollection 2021abstractalemtuzumab highly effective treatment relapsingremitting multiple sclerosis selectively targets cd52 antigen induce profound lymphocyte depletion followed recovery t b cells regulatory phenotypes previously showed regulatory t cell function restored cellular repletion little known functional capacity regulatory bcells peripheral blood monocytes repletion phase study clinicaltrialsgov id# nct03647722 simultaneously analyzed change composition function regulatory lymphocyte populations distinct monocyte subsets crosssectional cohorts ms patients prior 6 12 18 24 36 months first course alemtuzumab treatment found absolute number percentage cells regulatory b cell phenotype significantly higher treatment positivity correlated regulatory t cells addition b cells treated patients secreted higher levels il10 bdnf inhibited proliferation autologous cd4+cd25 t cell targets though little change monocytes populations overall following second annual course treatment cd14+ monocytes significantly increased antiinflammatory bias cytokine secretion patterns results confirmed immune system alemtuzumabtreated patients altered favor regulatory milieu involves expansion increased functionality multiple regulatory populations including b cells t cells monocytes showed first time functionally competent regulatory b cells reappear similar kinetics regulatory tcells whereas change antiinflammatory bias monocytes occur second treatment course findings justify future studies regulatory cell types following alemtuzumab treatment reveal insights mechanisms drug action identify key immunological predictors durable clinical efficacy alemtuzumabtreated patientspmid34777337 pmcpmc8581537 doi103389 fimmu2021706278,0.0
reduced exercise capacity patients systemic sclerosis associated lower peak tissue oxygen extraction cardiovascular magnetic resonanceaugmented cardiopulmonary exercise study background exercise intolerance systemic sclerosis ssc typically attributed cardiopulmonary limitations however problems skeletal muscle oxygen extraction fully investigated study used cardiovascular magnetic resonance cmr augmented cardiopulmonary exercise testing cmrcpet simultaneously measure oxygen consumption cardiac output allowed calculation arteriovenous oxygen content gradient recognized marker oxygen extraction performed cmrcpet 4 groups systemic sclerosis ssc systemic sclerosisassociated pulmonary arterial hypertension sscpah nonconnective tissue disease pulmonary hypertension ncpah healthy controlsmethodswe performed cmrcpet 60 subjects 15 group using supine ergometer following ramped exercise protocol exhaustion values oxygen consumption cardiac output oxygen content gradient well ventricular volumes obtained rest peakexercise subjects addition t1 t2 maps acquired rest recent clinical measures hemoglobin lung function 6min walk cardiac catheterization collected resultsall patient groups reduced peak oxygen consumption compared healthy controls p 0022 ssc sscpah groups reduced peak oxygen content gradient compared healthy controls p 003 conversely sscpah ncph patients reduced peak cardiac output compared healthy controls ssc patients p 0006 higher hemoglobin associated higher peak oxygen content gradient p 0025 higher myocardial t1 associated lower peak stroke volume p 0011 conclusionsreduced peak oxygen consumption ssc patients predominantly driven reduced oxygen content gradient sscpah patients amplified reduced peak cardiac outputtrial registration study registered clinicaltrialsgov protocol registration results system clinicaltrialsgov id 100358,0.0
altered substrate metabolism neurodegenerative disease new insights metabolic imaging abstractneurodegenerative diseases nds alzheimers disease ad parkinsons disease pd multiple sclerosis ms relatively common devastating neurological disorders example 6 million individuals living ad united states number projected grow 14 million year 2030 importantly ad pd ms characterized lack true diseasemodifying therapy able reverse halt disease progression addition existing standard care nds addresses symptoms disease therefore alternative strategies target mechanisms underlying neuropathogenesis disease much needed recent studies indicated metabolic alterations neurons glia commonly observed ad pd ms lead changes cell function can either precede protect disease onset progression specifically singlecell rnaseq studies shown ad progression tightly linked metabolic phenotype microglia key immune effector cells brain however analyses involve removing cells native environment performing measurements vitro influencing metabolic status therefore technical approaches can accurately assess cellspecific metabolism situ potential transformative understanding mechanisms driving ad review current understanding metabolism neurons glia homeostasis disease also evaluate recent advances metabolic imaging discuss emerging modalities fluorescence lifetime imaging microscopy flim potential determine metabolic perturbations may drive progression nds finally propose temporal regional cellspecific characterization brain metabolism afforded flim will critical first step rational design metabolismfocused interventions delay even prevent nds,0.0
ocular adverse events pharmacological treatment patients multiple sclerosisa systematic review literature abstractpurposethe aim study review scientific evidence describe ocular treatmentemergent adverse events teaes related pharmacological treatment patients multiple sclerosismethodsa systematic review literature conducted according preferred reporting items systematic reviews metaanalysis guidelines medline lilacs embase cochrane databases articles filtered based title abstract considering selection criteria subsequently filtered fulltext reading resulting articles evaluated using joanna briggs institute quality tools study characteristics results extracted presented structured tables conduct narrative synthesisresultsa total 2852 published articles extracted using strategy removing duplicates 2841 articles screened based title abstract 102 articles evaluated using quality tools 69 articles filtered fulltext reading search strategy 60 articles met inclusion criteria seven articles search update conducted manner included resulted 67 articles meeting inclusion criteria 11 experimental 56 observational therapies related ocular teaes alemtuzumab amantadine fingolimod steroids ctla4 ig estriol interferon natalizumab hyperbaric oxygen rituximab siponimod teriflunomide tovaxin fingolimod siponimod commonly associated macular edema interferon associated retinopathy alemtuzumab associated thyroid eye disease amantadine associated corneal edema steroids associated acute retinal necrosis opportunistic infections also found one lifethreatening caseconclusionsour search revealed different methodological assessments topic however longitudinal studies regarding ocular teaes related multiple sclerosis therapy necessary provide evidencebased recommendations especially understudied regions latin america africa physicians monitor ocular symptoms patients treated multiple sclerosis consider interdisciplinary approachsystematic review registrationprospero id crd42020106886,0.0
diagnosis alzheimer#39 s disease related dementia among people multiple sclerosis large cohort study usa abstractbackground alzheimernulls disease related dementia adrd multiple sclerosis ms two neurodegenerative diseases shared pathophysiological characteristics salient attribute adrd progressive decline cognitive function ms mainly known causing physical weakness vision loss muscle stiffness progressive cognitive decline however uncommon among ms patients many case reports ms indicative adrd coexistence due lack large epidemiological studies topic aimed examine time diagnosis adjusted hazard adrd using administrative claims data comparing adults without msmethods using 20072017 private claims data optum clinformatics data mart us identified adults 45+ ms diagnosis n6 151 well adults without ms comparison n916 143 propensity score matched people ms without n6 025 using age sex race ethnicity chronic conditions including cardiometabolic psychologic musculoskeletal us census division socioeconomic variables addition incidence estimates adrd diagnosis compared 4years survival models utilized quantify unadjusted fully adjusted adjusted propensitymatched hazard ratiosresults unmatched data revealed incidence earlyonset adrd diagnosis 7 times higher among adults 4564 years old ms 14 compared without 02 among older adults 65+ ms incident adrd 40 compared 33 among without ms adjusted survival models indicated adults ms substantially high risk earlyonset adrd diagnosis among 4564 years old unmatched hazard ratio hr 425 95 ci 340 532 matched hr 449 95 ci262769 among 65+ years old unmatched hr 139 95 ci 122 158 matched hr 126 104 154 conclusions individuals ms greater incidence risk early lateonset adrd diagnosis compared without ms clear whether greater risk due accelerated dementia risk least partially due clinical misdiagnosis advancements development clinical imaging biomarkers commonly used clinical settings facilitate future research topic,0.0
see feel identification illness perception schema association adaptation outcomes multiple sclerosis 5year prospective study plos one 2021 oct 28 16 10 e0258740 doi 101371 journalpone0258740 ecollection 2021abstractthe aim study assess role illness perception adaptation chronic disease among patients relapsingremitting multiple sclerosis rrms differences obtained configurations illness perception components four measurements model predictions values adaptation indicators ie depression anxiety quality life subsequent measurements analyzed illness representation assessed baseline via illness representation questionnairerevised adaptation indicatorsanxiety depression measured hads quality life measured msis29 measured baseline three times fiveyear period kmeans cluster analysis twoway repeated measures anova conducted group 90 patients 4889 women 5111 men subsequently mean values depression anxiety physical psychological quality life compared clusters using kruskallwallis test finally crosslagged panel modeled hads msis29 subscales measurement occasion t1t4 three different illness perception clusters anxious realistic fatalistic illness perception named aip rip fip composed differentiated depression anxiety quality life level age fip showed lowest adaptation outcomes small differences aip rip also significantly characterized highest age positive adaptation indicators related rip cluster model presented rather satisfactory fit 2 48 8105 cfi 968 tli 925 srmr 050 slightly inflated rmsea 087 90ci 053120 based initial measurements individual characteristics possible predict functioning patients several years patients aip covariance anxiety depression significant patients ripdepression anxiety patients fipdepression addition variables predictor subsequent measurements particular time intervals illustrating dynamics changes results highlight illness perceptions formed beginning rrms important process adaptation disease moreover showed differences adaptation outcomes supporting idea cognitive representation might important level psychological functioningpmid34710124 doi101371 journalpone0258740,0.0
myelin oligodendrocyte glycoproteinimmunoglobulin g csf clinical implication testing association disability neurol neuroimmunol neuroinflamm 2021 oct 28 9 1 e1095 doi 101212 nxi0000000000001095 print 2022 janabstractbackground objective investigate clinical relevance csf myelin oligodendrocyte glycoproteinimmunoglobulin g mogigg testing large multicenter cohortmethods multicenter cohort study paired serumcsf samples 474 patients suspected inflammatory demyelinating disease idd 11 referral hospitals included serum screening patients grouped seropositive myelin oligodendrocyte glycoprotein antibody associated disease mogad 31 aquaporin4iggpositive neuromyelitis optica spectrum disorder aqp4igg + nmosd 60 idds 217 multiple sclerosis ms 45 nonidds 121 screened csf mogigg compared clinical serologic characteristics patients uniquely positive mogigg csf seropositive patients mogadresults nineteen patients seropositive mogad 613 9 idds csf mog + idd 41 4 ms 89 none aqp4igg + nmosd nonidds tested positive csf mogigg clinical pathologic prognostic features patients uniquely positive csf mogigg nonms phenotype comparable seropositive mogad intrathecal mogigg synthesis observed onset disease shown 12 patients 4 28 seropositive 8 uniquely csf positive involvement either brain spinal cord csf mogigg titer corrected csf serum mogigg index serum mogigg titer associated disability csf pleocytosis level csf proteinsdiscussion csf mogigg found idd ms also ms idd ms csf mogigg positivity can support diagnosis mogad synthesis mogigg cns patients mogad can detected onset disease associated severity diseaseclassification evidence study provides class ii evidence presence csf mogigg can improve diagnosis mogad absence ms phenotype intrathecal synthesis mogigg associated increased disabilitypmid34711644 doi101212 nxi0000000000001095,1.0
palliative care needs patients multiple sclerosis southeast iran background due chronic nature multiple sclerosis palliative care can play significant role improving quality life wellbeing affected patients essential step developing appropriate palliative care patients determine types palliative care necessary different points view therefore study conducted compare palliative care needs nurses patients points view southeast iran 2017methodthis descriptiveanalytical crosssectional study conducted 154 nurses working neurology wards teaching hospitals associated kerman university medical sciences 132 patients multiple sclerosis referred hospitals southeast iran data collected using questionnaire assessing palliative care needs patients multiple sclerosis pearson correlation coefficient independent ttest anova chisquare mannwhitney kruskalwallis tests used examine dataresultsboth nurses patients mentioned palliative needs patients multiple sclerosis terms physical social spiritual psychological economic dimensions respectively results showed significant difference two groups dimensions palliative needs p 00001 conclusiongiven differences patients nurses prioritize palliative care needs essential consider different dimensions palliative needs patients multiple sclerosis,0.0
motor symptoms quality life relapsingremitting multiple sclerosis patients specialized center south brazil abstract background spasticity fatigue muscle weakness changes gait main motor symptoms multiple sclerosis ms changes can interfere patients quality life objective characterize motor quality life symptoms patients relapsingremitting multiple sclerosis specialized center methods fifty five patients neuroimmunology outpatient clinic hospital de clnicas de porto alegre evaluated fatigue fatigue severity scale fss walking ability functional ambulation categories fac impact ms walking multiple sclerosis walking scale12 msws12 walking speed 10meter walk test 10mwt times 25foot walk test t25fw functional independence barthel index bi functional mobility timed go tug quality life multiple sclerosis impact scale msis29 results patients mostly women 691 average age 433 121 years old time since diagnosis 82 53 years edss average 43 13 bi mean 966 57 points 80 patients fac 5 msis29 patients higher average score psychological scale 195267 physical scale 102236 patients 691 presented fatigue conclusion patients preserved functional independence functional walking ability presence fatigue minimal impact ms patients quality life,0.0
taar1 expression human macrophages brain tissue potential novel facet ms neuroinflammation int j mol sci 2021 oct 27 22 21 11576 doi 103390 ijms222111576abstracttaar1 neuroregulator emerging evidence suggesting role immunomodulation multiple sclerosis ms immunemediated demyelinating disease central nervous system investigate taar1 expression human primary monocytes peripherallyderived macrophages ms brain tissue rtqpcr used assess taar1 levels ms monocytes using previously validated antihuman taar1 antibody fluorescence microscopy taar1 protein visualized lipopolysaccharidestimulated basal human macrophages well macrophage microglia populations surrounding bordering within mixed active inactive ms lesion vivo taar1 mrna expression significantly lower ms monocytes compared age sexmatched healthy controls vitro taar1 protein showed predominant nuclear localization quiescent control macrophages shift diffuse intracellular distribution following lipopolysaccharideinduced activation brain tissue taar1 protein predominantly expressed macrophages microglia within border region mixed active inactive ms lesions considering taar1mediated antiinflammatory effects previously reported decreased mrna ms patients suggests possible pathophysiologic relevance shift taar1 localization following proinflammatory activation suggests function altered proinflammatory states taar1expressing macrophages microglia bordering ms lesion supports taar1 novel pharmacological target cells directly implicated ms neuroinflammationpmid34769007 doi103390 ijms222111576,1.0
estimation sample size randomized controlled trials multiple sclerosis studying annualized relapse rates systematic review abstractbackgroundin multiple sclerosis ms studies appropriate model distribution number relapses shown negative binomial nb distributionobjectiveto determine whether samplesize estimation sse analysis annualized relapse rates arrs randomized controlled trials rcts aligned compare sse normal nb distributionsmethodssystematic review phase 3 4 rcts primary endpoint arr relapsing remitting ms published since 2008 preselected major medical journals pubmed search performed 30 november 2020 checked whether sse arr analyses congruent also performed standardized fixed number arms overdispersion sses using data collected studiesresultstwenty articles 22 studies selected nb distribution quasipoisson used sse 7 22 studies whereas 21 22 used arr analyses sse relying nb regression necessitated smaller sample size 21 22 calculationsconclusionsse rarely performed using appropriate model however use nb model recommended optimize number included patients congruent final analysis,0.0
homozygosity haplotype wholeexome sequencing analysis identify potentially functional rare variants involved multiple sclerosis among sardinian families curr issues mol biol 2021 oct 27 43 3 17781793 doi 103390 cimb43030125abstractmultiple sclerosis ms complex multifactorial autoimmune disease whose sex ageadjusted prevalence sardinia italy among highest worldwide date 233 loci associated ms almost 20 risk heritability attributable common genetic variants many lowfrequency rare variants remain discovered aimed contribute understanding genetic basis ms investigating potentially functional rare variants end analyzed thirteen multiplex sardinian families immunochip genotyping data five families whole exome sequencing wes data also available firstly performed nonparametric homozygosity haplotype analysis identifying region common ancestor rca potential diseaselinked rca searched presence rare variants shared affected individuals analyzing wes data found variant 43181034 t g splicing region exon 27 cul9 ii variant 50245517 c splicing region exon 16 atp9a iii nonsynonymous variant 43223539 c exon 9 ttbk1 iv nonsynonymous variant 42976917 c exon 9 ppp2r5d v variant 109859349109859354 3utr myo16pmid34889895 doi103390 cimb43030125,0.0
crosstalk autophagy inhibitors endosomerelated secretory pathways challenge autophagybased treatment solid cancers abstractautophagy best known role organelle protein turnover cell quality control metabolism autophagic machinery however also adapted enable protein trafficking unconventional secretory pathways organelles autophagosomes multivesicular bodies delivering cargo lysosomes degradation can change mission fusion lysosomes fusion plasma membrane followed secretion cargo cell factors key signalling functions enter conventional secretory pathway can secreted autophagymediated mannerpositive clinical results autophagy inhibitors encouraging nevertheless becoming clear autophagy inhibition even within cancer type can affect cancer progression differently even nextgeneration inhibitors autophagy can significant nonspecific effects impacts endosomerelated secretory pathways secretion extracellular vesicles evs many studies suggest cancer cells release higher amounts evs compared nonmalignant cells makes effect autophagy inhibitors evs secretion highly important attractive anticancer therapy review article discuss different inhibitors autophagy may influence secretion evs summarize nonspecific effects autophagy inhibitors focus endosomerelated secretory pathways modulation autophagy significantly impacts quantity evs also content can deep impact resulting protumourigenic anticancer effect autophagy inhibitors used antineoplastic treatment solid cancers,0.0
longitudinal analysis regional brain changes antinmdar encephalitis case report background antinmda receptor encephalitis immunemediated disorder characterized antibodies glun1 subunit nmda receptor increasingly recognized treatable cause childhood epileptic encephalopathy adults disorder associated reversible changes brain volume course treatment recovery children little known time course associated imaging manifestationscase presentationa previously healthy 20monthold boy presented firsttime unprovoked seizures dysautonomia dyskinesia paraneoplastic workup negative csf positive antinmdar antibodies patients clinical condition waxed waned 14month course treatment first secondline immunotherapies including steroids ivig rituximab cyclophosphamide serial brain mris scans obtained 5 time points spanning period showed abnormal signal enhancement remarkable cycles reversible regional cortical volume loss scans included identical 1mm resolution 3d t1weighted sequences obtained 3 t scanner using novel longitudinal processing stream freesurfer6 reuter m et al neuroimage 61140218 2012 quantified rate change cortical volume vertex volume change per month consecutive scans correlated changes time course patients treatment clinical response found regionally specific changes cortical volume 7 per month preferentially affected frontal occipital lobes paralleled patients clinical course clinical decline associated volume loss clinical improvement associated volume gainconclusionsour results suggest reversible cortical volume loss antinmda encephalitis regional specificity mirrors many clinical symptoms associated disorder tracks dynamics disease severity time case illustrates quantitative morphometric techniques can applied clinical imaging data reveal patterns brain change may provide insight disease pathophysiology widespread application approach might reveal regional temporal patterns specific different types autoimmune encephalitis providing tool diagnosis surrogate marker monitoring treatment response,0.0
optical coherence tomography differential diagnosis patients multiple sclerosis patients mri nonspecific white matter lesions sensors basel 2021 oct 27 21 21 7127 doi 103390 s21217127abstractin differential diagnosis nonspecific white matter lesions nswmls detected magnetic resonance imaging mri multiple sclerosis ms taken consideration optical coherence tomography oct promising tool applied differential diagnostic process ms tested whether oct may useful distinguishing ms nswmls patients patients ms n 41 nswmls n 19 following oct parameters measured thickness peripapillary retinal nerve fibre layer prnfl superior inferior nasal temporal segments thickness ganglion cellinner plexiform layer gcipl thickness macular rnfl mrnfl macular volume mv ms patients gcipl significantly lower nswmls patients p 0024 additionally ms patients mrnfl significantly lower nswmls patients p 0030 average segmental prnfl mv differ ms nswmls patients p 005 gcipl macular rnfl thinning significantly influenced risk ms 186 95 ci 27 253 274 95 ci 45 623 reduced gcipl thickness appeared best predictor ms conclude oct may helpful differential diagnosis ms nswmls patients realworld settingspmid34770434 doi103390 s21217127,0.0
canadian prospective cohort study understand progression multiple sclerosis canproco rationale aims study design background neurological disability progression occurs across spectrum people living multiple sclerosis ms although handful diseasemodifying treatments approved use progressive phenotypes ms treatments substantially modify course clinical progression ms characterizing determinants clinical progression can inform development novel therapeutic agents treatment approaches target progression ms one greatest unmet needs clinical practice canada one worlds highest rates ms publiclyfunded health care system represents optimal country achieve indepth analysis progression accordingly overarching aim canadian prospective cohort study understand progression ms canproco evaluate wide spectrum factors associated clinical onset rate disease progression ms describe factors relate one another influence progressionmethodscanproco prospective observational cohort study investigators specializing epidemiology neuroimaging neuroimmunology health services research health economics canprocos study design approved international review panel comprised content experts key stakeholders one thousand individuals radiologicallyisolated syndrome relapsingremitting ms primaryprogressive ms within 1015 years disease onset will recruited 5 academic ms centres canada participants will undergo detailed clinical evaluation annually 5 years including advanced appbased clinical data collection subset participants within 510 years disease onset n 500 blood cerebrospinal fluid research mris will collected allowing integrated indepth evaluation factors contributing progression ms multiple perspectives factors interest range biological measures eg singlecell rnasequencing mribased microstructural assessment participant characteristics selfreported performancebased clinicianassessed healthsystem based micro macroenvironmental factorsdiscussionhalting progression ms remains fundamental need improve lives people living ms achieving requires leveraging transdisciplinary approaches better characterize clinical progression occurs canproco pioneering multidimensional cohort study aiming characterize determinants inform development implementation efficacious effective interventions,0.0
development validation clinical usefulness prognostic model relapse relapsingremitting multiple sclerosis prognosis occurrence relapses individuals relapsingremitting multiple sclerosis rrms common subtype multiple sclerosis ms support individualized decisions diseas,0.0
vgf biomarker therapeutic target neurodegenerative psychiatric diseases brain commun 2021 oct 27 3 4 fcab261 doi 101093 braincomms fcab261 ecollection 2021abstractneurosecretory protein vgf nonacronymic belongs granin family neuropeptides vgf vgfderived peptides repeatedly identified wellpowered welldesigned multiomic studies dysregulated neurodegenerative psychiatric diseases new therapeutics urgently needed devastating costly diseases new biomarkers improve disease diagnosis mechanistic understanding list 537 genes involved alzheimers disease pathogenesis vgf highlighted accelerating medicines partnership alzheimers disease potential therapeutic target greatest interest vgf levels consistently decreased brain tissue csf samples patients alzheimers disease compared controls levels correlate disease severity alzheimers disease pathology brain vgf exists multiple functional vgfderived peptides fulllength human vgf1615 undergoes proteolytic processing prohormone convertases proteases regulated secretory pathway produce least 12 active vgfderived peptides cell animal models vgfderived peptides linked energy balance regulation neurogenesis synaptogenesis learning memory depressionrelated behaviours throughout development adulthood cterminal vgfderived peptides tlqp62 vgf554615 tlqp21 vgf554574 differential effects alzheimers disease pathogenesis neuronal microglial activity learning memory tlqp62 activates neuronal cellsurface receptors regulates longterm hippocampal memory formation tlqp62 also prevents immunemediated memory impairment depressionlike anxietylike behaviours mice tlqp21 binds microglial cellsurface receptors triggering microglial chemotaxis phagocytosis actions reported reduce amyloid plaques decrease neuritic dystrophy transgenic mouse model familial alzheimers disease expression differences vgfderived peptides also associated frontotemporal lobar dementias amyotrophic lateral sclerosis lewy body diseases huntingtons disease pain schizophrenia bipolar disorder depression antidepressant response review summarizes current knowledge highlights questions future investigation regarding roles vgf dysregulation neurodegenerative psychiatric disease finally potential vgf vgfderived peptides biomarkers novel therapeutic targets neurodegenerative psychiatric diseases highlightedpmid34778762 pmcpmc8578498 doi101093 braincomms fcab261,0.0
molecular mechanisms muscle fatigue int j mol sci 2021 oct 27 22 21 11587 doi 103390 ijms222111587abstractmuscle fatigue mf declines capacity muscles complete task time constant load mf usually shortlasting reversible experienced feeling tiredness lack energy leading causes shortlasting fatigue related overtraining undertraining deconditioning physical injury conversely mf can persistent serious associated pathological states following chronic exposure certain medication toxic composites conjunction chronic fatigue muscle feels floppy force generated muscles always low causing individual feel frail constantly leading cause underpinning development chronic fatigue related muscle wasting mediated aging immobilization insulin resistance highfat dietary intake pharmacologically mediated peroxisome proliferatoractivated receptor ppar agonism diseases associated systemic inflammation arthritis sepsis infections trauma cardiovascular respiratory disorders heart failure chronic obstructive pulmonary disease copd chronic kidney failure muscle dystrophies muscle myopathies multiple sclerosis recently coronavirus disease 2019 covid19 primary outcome displaying chronic muscle fatigue poor quality life type fatigue represents significant daily challenge affected national health authorities financial burden attached patient support although origin chronic fatigue multifactorial mf illness conditions intrinsically linked occurrence muscle loss sequence events leading chronic fatigue can schematically denoted trigger genetic pathological molecular outcome within muscle cell muscle wasting loss muscle function occurrence chronic muscle fatigue present review will highlight discuss current knowledge molecular mechanisms contribute upregulation muscle wasting thereby helping us understand prevent treat debilitating conditionpmid34769017 doi103390 ijms222111587,0.0
longterm prognosis predictors epilepsy retrospective study 820 patients background investigate prognosis predictors seizure control epileptic patients chinamethodseight hundred twenty patients epilepsy visited xuanwu hospital october 2017 january 2020 enrolled clinical information patients obtained retrospectively reviewing medical records prognostic measures seizure control included remission relapse occurrence drug resistance relationship prognosis seizure control factors demographics clinical characteristics initial electroencephalography eeg features investigatedresultsa total 503 613 patients experienced 1year remission 330 493 669 2year remission idiopathic type epilepsy p 0001 normal eeg p 005 number antiepileptic drugs p 005 seizure frequency 1 month p 0001 first arrival predicted remission independently 503 patients achieved 1year remission 184 366 experienced relapse due external reversible causes 58 patients unknown reversible triggers 126 patients factors found associated relapse p 005 end study 322 patients 393 developed drug resistance development drug resistance associated following factors symptomatic aetiology epilepsy epileptiform abnormality eeg number antiepileptic drugs seizure frequency 1 month first arrival p 0001 symptomatic epilepsy patients meningitis encephalitis p 0007 likely develop drugresistant epilepsy causesconclusionsremission common process type epilepsy idiopathic symptomatic eeg features seizure frequency treatment history first arrival related remission terminal drug resistance among various causes symptomatic epilepsy meningitis encephalitis associated worst prognosis epilepsy,0.0
prevalence factors associated receipt provider recommendation influenza vaccination uptake influenza vaccination pregnancy crosssectional study background seasonal influenza vaccination recommended pregnant women germany since 2010 aim study examine prevalence determinants receipt provider recommendation influenza vaccination well influenza vaccination uptake pregnancymethodswe analysed data kuno kids health study prospective birth cohort study period 5th july 2015 27th june 2018 data collected participating mothers interview questionnaire according andersens behavioural model health services use potential influencing factors describing circumstances characteristics mothers pregnancies potentially affecting whether women receive recommendation vaccination whether utilize influenza vaccination classified three domains predisposing characteristics enabling resources need using multivariable logistic regression models odds ratios corresponding 95 confidence intervals 95 ci calculatedresultsas combined result across three flu seasons 368 1814 203 women received influenza vaccination recommendation pregnancy highrisk pregnancy increased odds receiving vaccination recommendation 13 95 ci 1016 p 0045 contrast pregnancy onset summer 07 95 ci 0510 p 0027 autumn 04 95 ci 0305 p 0001 winter 05 95 ci 0306 p 0001 compared spring well mothers birthplace outside germany 06 95 ci 0409 p 0023 reduced chance getting vaccination recommendationtwo hundred fortytwo one thousand eight hundred sixtyfive 13 women vaccinated influenza pregnancy received vaccination recommendation strongly associated vaccination uptake 378 95 ci 255559 p 0001 higher health literacy status also associated higher chance vaccination uptake 17 95 ci 1226 p 0008 whereas pregnancy onset autumn compared spring reduced chance 05 95 ci 0308 p 0008 conclusionsat 13 uptake rate influenza vaccination low received recommendation vaccinate strongly associated uptake one fifth mothers report recommendation raising awareness physicians regarding vaccinating pregnancy seems essential importance increase vaccine uptake prevent influenzarelated complications pregnant women,0.0
development validation disease specific problems questionnaire patients multiple sclerosis background patients multiple sclerosis face numerous problems lifetime selfreport measurement disease specific problems required developed patients multiple sclerosis based different cultural factors accordingly can advance understanding diseasespecific problems care planning well improving coping ways quality life study aimed develop validate scale diseasespecific problems multiple sclerosismethodsthis exploratory sequential mixed method study conducted three phases correspondingly first phase concept diseasespecific problems defined using content analysis approach patients ms second phase item pool generated findings first phase third phase psychometric properties scale including face content construct validity reliability evaluatedresultsafter examining validity reliability 28 items developed final questionnaire well performing factor analysis five factors revealed follows physical problems psychological problems emotional problems family problems socioeconomic problems internal consistency stability questionnaire calculated 082 090 respectively indicating excellent reliabilityconclusionthe 28item questionnaire valid reliable measurement level disease specific problems iranian people ms,0.0
increased risk multiple sclerosis associated hladrb11501 smoking modified alcohol consumption sci rep 2021 oct 27 11 1 21237 doi 101038 s4159802100578yabstractprevious studies observed inverse association alcohol consumption multiple sclerosis ms risk aimed investigate possible interactions alcohol consumption msassociated human leukocyte antigen hla genes smoking regarding ms risk used swedish populationbased casecontrol study 2059 incident cases 2887 controls matched age sex residential area subjects different genotypes alcohol consumption habits compared regarding ms risk calculating odds ratios 95 confidence intervals using logistic regression models interaction additive scale nondrinking genotype smoking assessed calculating attributable proportion due interaction ap dosedependent inverse association alcohol consumption ms risk p trend 00001 potentiating effect observed nondrinking presence drb11501 ap 03 95 ci 0205 similar magnitude irrespective smoking habits nondrinking also interacted smoking increase ms risk ap 02 95 ci 00604 nondrinking interacts drb11501 smoking increase risk ms better understanding mechanisms behind findings may help define ways achieve protection ms means alcohol consumptionpmid34707149 doi101038 s4159802100578y,0.0
comparison sex hormones serum level women recurrent aphthous stomatitis healthy population crosssectional study background study aimed evaluate sex hormonal serum level patients recurrent aphthous stomatitis compare healthy participants methodsthis crosssectional study done patients recurrent aphthous stomatitis referred shiraz dental faculty oral maxillofacial medicine department 20182019 non menopause women recurrence least 3 lesions per year enrolled study mean serum level fsh lh prl prolactin testosterone dht dihydrotestosterone dheas dehydroepiandrosterone sulfate estradiol progesterone 30 participants group case control measured compared data analyzed spss version 18 independent ttest mannwhitney u test spearmans correlation coefficient test chisquare test fishers testresultsthe mean serum level dheas patients recurrent aphthous stomatitis ras significantly lower control group p value 002 addition dheas mean serum level testosterone lower evaluation group although difference significant p value 0057 considering effect age mean serum level sex hormones results revealed dheas mean serum level decreased increasing age participants patients ras p value 0018 number participants abnormal range testosterone p value 00001 progesterone p value 0037 serum level significantly patients ras frequency ras year show significant relationship serum level evaluated hormonesconclusionthe patients ras lower serum level dheas mean serum level testosterone progesterone significantly abnormal ras patients,0.0
effects covid19 pandemic quality life survey mildly disabled multiple sclerosis patients east mediterr health j 2021 oct 27 27 10 10011006 doi 1026719 emhj21034abstractbackground almost everyones healthrelated quality life hqol can affected huge health problem like covid19 pandemicaims assessed shortterm impact covid19 pandemic hqol multiple sclerosis ms patients tabriz islamic republic iranmethods printed version msspecific hqol questionnaire completed patients neurology department university hospital tabriz scores pandemic 2019 2020 comparedresults recruited 50 patients study although overall physical 6929 + sd 1659 6840 + sd 2095 mental health 6736 + sd 1902 6676 + sd 2270 composite scores decreased slightly second stage however change statistically significant p 067 p 083 severity ms associated changes mental physical health compositesconclusions effect pandemic hqol mildly disabled ms patients statistically significantpmid34766326 doi1026719 emhj21034,0.0
adaptation patients diagnosed human papillomavirus grounded theory study background human papillomavirus common cause sexually transmitted diseases various studies report positive human papillomavirus diagnosis results psychosexual issues infected reduces quality life however adaptation infected addressed yet present study aims identify process individuals infected human papillomavirus adapt diseasemethodthis qualitative work research grounded theory design setting study skin clinic shahid faghihi hospital shiraz participants consisted 27 individuals 18 patients 3 doctors 2 counselors 4 spouses patients subjects selected via purposeful theoretical sampling method data saturation reached data collected facetoface indepth semistructured interviews april 2019 december 2020 collected data analyzed using corbin strausss method 2015 maxqda 2018resultsthe theory emerged data trying maintain resilience absence psychological security analysis data showed main concern participants adapting diagnosis human papillomavirus life stress stigma ignorance found contextual condition paradox support intervening condition patients adaptation patients action interaction responses main concern context question emotional confrontation maintaining resilience outcome oscillation tension tranquilityconclusionthe present study explains process patients human papillomavirus adapt condition identification concerns patients human papillomavirus factors affect adaptation can help healthcare policymakers providers develop effective support plans order increase patients quality life early interventions eg counseling care providers modify behaviors toward alleviating psychosexual tension infected can facilitate adaptation infected decrease consequences infection themgraphical abstract,0.0
autoimmunity increases susceptibility mortality sepsis immunohorizons 2021 oct 26 5 10 844854 doi 104049 immunohorizons2100070abstractwe recently demonstrated sepsis influences subsequent development experimental autoimmune encephalomyelitis eae presented conceptual advance understanding postsepsis chronic immunoparalysis state however reverse scenario autoimmunity prior sepsis defines highrisk patient population whose susceptibility sepsis remains poorly defined study present retrospective analysis university iowa hospital clinics patients demonstrating increased sepsis prevalence among multiple sclerosis ms relative nonms patients interrogate autoimmune disease influences host susceptibility sepsis wellestablished murine models ms sepsis eae cecal ligation puncture respectively used eae relative noneae mice highly susceptible sepsisinduced mortality elevated cytokine storms results recapitulated lps streptococcus pneumoniae sepsis models work highlights relevance identifying highly susceptible patient populations expands growing body literature host immune status time septic insult potent mortality determinantpmid34702761 doi104049 immunohorizons2100070,0.0
multicenter crosssectional french study impact covid19 neuromuscular diseases background due health condition patients neuromuscular diseases nmd greater risk developing serious complications covid19 objective study analyze prevalence covid19 among nmd patients risk factors impact severity first wave pandemic clinical data collected nmdcovid19 patients march 25 2020 may 11 2020 anonymous survey carried expert physicians french health care network filnemus resultsphysicians reported 84 patients including 34 myasthenia gravis 27 myopathy 23 neuropathy covid19 effect nmd 48 58 patients 48 58 patients developed low covid19 severity covid19 caused death 9 11 nmd patients diabetic patients greater risk dying patients diabetes hypertension severe forms nmd higher risk developing moderate severe form covid19 cohort corticosteroids immunosuppressants significantly associated higher covid19 severity acquired nmdconclusionduring period small percentage french nmd patients affected covid19 compared general french population covid19 limited shortterm effect diabetes hypertension severe degree nmd identified risk factors unfavorable outcome following covid19 conversely cohort patients acquired nmd corticosteroids immunosuppressants appear risk factors severe covid19,0.0
diabetes mellitus exacerbates experimental autoimmune myasthenia gravis via modulating adaptive innate immunity background diabetes mellitus dm common concomitant disease lateonset myasthenia gravis mg however impacts dm progression lateonset mg unclearmethodsin study examined immune response experimental autoimmune myasthenia gravis eamg rats dm phenotype function spleen lymph nodes determined flow cytometry serum antibodies tfh cells germinal center b cells determined elisa flow cytometry roles advanced glycation end products ages regulating tfh cells explored vitro coculture assaysresultsour results indicated clinical scores eamg rats worse diabetes rats compared control due increased production antir97116 antibody antibodysecreting cells furthermore diabetes induced significant upregulation tfh cells subtypes tfh1 tfh17 cells provide assistance antibody production total percentages b cells increased activated statue improved expression costimulatory molecules cd80 cd86 found cd4+ tcell differentiation shifted treg cells towards th1 th17 dm+eamg group compared eamg group addition innate immunity diabetic eamg rats displayed cxcr5 expression nk cells however expression cxcr5 nkt cells downregulated increased percentages nkt cells dm+eamg group ex vivo studies indicated tfh cells upregulated ages instead hyperglycemia upregulation mediated existence b cells mechanism might attributed elevated molecule cd40 b cellsconclusionsdiabetes promoted adaptive innate immunity exacerbated clinical symptoms eamg rats considering effect diabetes therapy reducing blood glucose levels mg patients might improve clinical efficacy suppressing innate adaptive immune responses additional studies needed confirm effect glucose ages reduction seek treatment mg,0.0
neuroprotective potential chrysin mechanistic insights therapeutic potential neurological disorders molecules 2021 oct 26 26 21 6456 doi 103390 molecules26216456abstractchrysin herbal bioactive molecule exerts plethora pharmacological effects including antioxidant antiinflammatory neuroprotective anticancer growing body evidence highlighted emerging role chrysin variety neurological disorders including alzheimers parkinsons disease epilepsy multiple sclerosis ischemic stroke traumatic brain injury brain tumors based results recent preclinical studies evidence studies humans review focused molecular mechanisms underlying neuroprotective effects chrysin different neurological diseases addition potential challenges opportunities chrysins inclusion neurotherapeutics repertoire critically discussedpmid34770864 doi103390 molecules26216456,1.0
clinical neurophysiological mri markers fampridine responsiveness multiple sclerosisan explorative study front neurol 2021 oct 26 12758710 doi 103389 fneur2021758710 ecollection 2021abstractobjective persons multiple sclerosis pwms already established responders nonresponders fampridine treatment compared terms disability measures physical cognitive performance tests neurophysiology magnetic resonance imaging mri outcomes 1year explorative longitudinal study materials methods data 1year longitudinal study analyzed examinations consisted timed 25foot walk test t25fw six spot step test ssst ninehole peg test 9hpt five times sittostand test 5sts symbol digit modalities test sdmt transcranial magnetic stimulation tms elicited motor evoked potentials mep examining central motor conduction times cmct peripheral motor conduction times pmct amplitudes electroneuronography eng lower extremities brain structural mri measures results fortyone responders eight nonresponders fampridine treatment examined intergroup differences except pmct nonresponders prolonged conduction times compared responders fampridine six spot step test associated cmct throughout study 1 year cmct prolonged cortical mep amplitudes decreased groups pmct eng change throughout study cmct associated expanded disability status scale edss 12item multiple sclerosis walking scale msws12 sdmt associated number t2weighted lesions lesion load lesion load normalized brain volume conclusions peripheral motor conduction time prolonged nonresponders fampridine compared responders transcranial magnetic stimulationelicited meps sdmt can used markers disability progression lesion activity visualized mri respectively clinical trial registration wwwclinicaltrialsgov identifier nct03401307pmid34764932 pmcpmc8576138 doi103389 fneur2021758710,0.0
neuronal cholesterol synthesis essential repair chronically demyelinated lesions mice cell rep 2021 oct 26 37 4 109889 doi 101016 jcelrep2021109889abstractastrocytederived cholesterol supports brain cells physiological conditions however demyelinating lesions astrocytes downregulate cholesterol synthesis cholesterol essential remyelination originate cellular sources show repair following acute versus chronic demyelination involves distinct processes particular chronic myelin disease recycling lipids often defective de novo neuronal cholesterol synthesis critical regeneration gene expression profiling genetic lossoffunction experiments comprehensive phenotyping provide evidence neurons increase cholesterol synthesis chronic myelin disease models patients multiple sclerosis ms mouse models neuronal cholesterol facilitates remyelination specifically triggering oligodendrocyte precursor cell proliferation data contribute understanding disease progression implications therapeutic strategies patients mspmid34706227 doi101016 jcelrep2021109889,1.0
relationship cognitive impairment cognitive fatigue visual evoked potential latency people multiple sclerosis abstractbackground fatigue people multiple sclerosis pwms can impact physical cognitive psychosocial domains daily life experience fatigue pwms thought originate central nervous system particularly domain cognitive fatigue tested hypothesis fatigue scores pwms significantly associated index neural activity latency p100 visual evoked potential vep line notion centralized origin fatigue predicted prolonged vep latency associated greater fatigue relationship pronounced within domain cognitive fatigue methods pwms n249 completed modified fatigue impact scale global physical cognitive psychosocial scales mfis fatigue severity scale vep latency obtained using alternating checkerboard paradigm also examined influence depression beck depression inventory second edition bdiii cognitive functioning neurotrax testing battery vep fatigue relationship results surprisingly observed earlier later vep latency significantly associated higher mfis cognitive score negative relationship vep latency cognitive fatigue evident pwms poor cognitive performance measured latent variable reflected attention executive function information processing speed motor skills significant relationship observed pwms exhibited good performance measure conclusions findings can interpreted within metacognitive framework greater fatigue may perceived neural performance level mental effort expended translate efficient cognitive performance cognitive fatigue may particularly salient pwms neural resources unable compensate cognitive difficulties mismatch expectation occur occur cognitive performance may key feature experience cognitive fatigue pwms,0.0
early diagnosis treatment associated improved outcomes patients multiple sclerosis neurology 2021 sep 14101212 wnl0000000000012738 doi 101212 wnl0000000000012738 online ahead printno abstractpmid34521689 doi101212 wnl0000000000012738,0.0
effect changes ms diagnostic criteria 25 years time treatment prognosis patients clinically isolated syndrome neurology 2021 sep 14101212 wnl0000000000012726 doi 101212 wnl0000000000012726 online ahead printabstractobjectives explore whether time diagnosis time treatment initiation age reach disability milestones changed patients clinically isolated syndrome cis according different multiple sclerosis ms diagnostic criteria periodsmethods retrospective study based data prospective collected barcelonacis cohort 1994 2020 patients classified five periods according different ms criteria time ms diagnosis treatment initiation evaluated age ms patients reached edss 30 assessed cox regression analysis according diagnostic criteria periods finally order remove classical will rogers phenomenon use different ms criteria time might result changes prognosis 2017 mcdonald criteria applied age edss 30 also assessed cox regressionresults 1174 patients included median time cis ms diagnosis cis treatment initiation showed 77 82 reduction poser mcdonald 2017 diagnostic criteria periods respectively patients given age diagnosed recent diagnostic criteria periods lower risk reaching edss 30 patients age diagnosed earlier diagnostic periods reference category poser period adjusted hazard ratio ahr 047 95 confidence interval 024090 mcdonald 2001 ahr 025 012054 mcdonald 2005 ahr 030 012075 mcdonald 2010 ahr 007 001045 mcdonald 2017 earlytreatment patients displayed ahr 053 033085 reaching age edss 30 compared latetreatment changes prognosis together earlytreatment effect maintained excluding possible bias derived use different diagnostic criteria time called will rogers phenomenon conclusion continuous decrease time ms diagnosis treatment initiation observed across diagnostic criteria periods overall patients diagnosed recent diagnostic criteria periods displayed lower risk reaching disability importantly prognostic improvement maintained discarding will rogers phenomenon early treatment appears likely contributing factorpmid34521693 doi101212 wnl0000000000012726,0.0
multiple sclerosis microglia monocytes macrophagemediated demyelination j neuropathol exp neurol 2021 sep 23nlab083 doi 101093 jnen nlab083 online ahead printabstractthis study examined roles microglia monocytes myelin destruction patients early multiple sclerosis ms twentytwo cases studied clinical duration 9 weeks 10 cases twenty myeloid cell subtypes categories identified including 2 cell types known previously occur demyelinating diseases commencing myelin breakdown plaques perivascular subpial tissues occurred immediate presence infiltrating monocytes effected homogeneous population iggpositive fc receptorbearing early phagocytes interacting abnormal myelin oligodendrocyte apoptosis observed intact myelinated tissue bordering areas active demyelination capillaries cerebral cortex plugged large numbers monocytes common acute cases ms patient neuromyelitis optica variant extreme systemic recruitment monocytes ms patient progressive disease microglial nodules centered mhciipositive capillaries plugged monocytes present cerebral cortex constitutes new gray matter lesion mspmid34553215 doi101093 jnen nlab083,1.0
increased radiographic progression distal hand osteoarthritis occurring biologic dmard monotherapy concomitant rheumatoid arthritis abstractobjectivesa considerable proportion patients rheumatoid arthritis ra also suffer hand osteoarthritis oa assess association conventional synthetic cs biological b diseasemodifying antirheumatic drugs dmards radiographic distal interphalangeal dip oa patients ramethodsadult ra patients longitudinal swiss registry rheumatic diseases 2 hand radiographs included first radiograph followed outcome last radiograph patients grouped two cohorts based whether dip oa present absent cohort entry cohorts 1 2 respectively modified kellgrenlawrence scores kls obtained evaluating dip joints severity osteophytes joint space narrowing subchondral sclerosis erosions kls 2 1 dip joint indicated incident existing oa increase 1 kls 1 dip joint indicated progression existing dip oa timevarying cox regression generalized estimating equation gee analyses performed estimated hazard ratios hrs odds ratios ors 95 confidence intervals ci dip oa incidence cohort 2 progression cohort 1 bdmard monotherapy bdmard csdmard combination therapy past never dmard use compared csdmard use post hoc analyses descriptively analytically assessed individual kls features cohort 1resultsamong 2234 ra patients 5928 radiographs 1340 patients dip oa baseline cohort 1 radiographic progression dip oa characterized new progressive osteophyte formation 666 524 joint space narrowing 379 275 subchondral sclerosis 238 178 erosions 62 43 bdmard monotherapy increased risk radiographic dip oa progression compared csdmard monotherapy adjusted hr 134 95 ci 107169 risk significant csdmard bdmard combination users hr 112 95 ci 096131 absent past dmard users hr 096 95 ci 066141 significantly lower among never dmard users hr 054 95 ci 033090 osteophyte progression hr 174 95 ci 111274 significantly increased oa feature bdmard use compared csdmard use 894 patients without initial dip oa cohort 2 risk incident oa differ treatment groups results gee analyses corroborated findingsconclusionsthese realworld ra cohort data indicate monotherapy bdmards associated increased radiographic progression existing dip oa incident dip oa,0.0
information processing speed prognostic marker physical impairment progression patients multiple sclerosis abstractbackgroundprediction disability progression patients ms pwms challenging far scarce evidence exists suggesting knowledge cognitive performance may potentially improve prediction physical impairment disability progression ms therefore wanted assess prognostic value cognitive performance regarding physical impairment disability progression pwmsmethods85 patients 64 female 60 relapseremitting ms mean age3678 963 years underwent clinical neuropsychological brief repeatable battery neuropsychological test brbn brain mri t1weighted t2weighted flair images assessment baseline average 7 years sd375 followup assessed physical impairment annualized disability progression disability progression divided followup duration using expanded disability status scale edss compare patients mild physical impairment edss25 patients moderate severe physical impairment edss30 used edss score 30 cutoff silent progression defined edss worsening least 05 absence relapses inflammation relapsingremitting msresultsin hierarchical regression models method stepwise forward performance information processing speed significant independent predictor physical impairment edss30 followup model r0671 b146 or023 p0001 annualized disability progression adjusted model r0257 026 95 ci 0066 0008 p0012 addition demographics age education individual followup time clinical edss disease duration clinical phenotype annualizedrelapserate mri measures brain volumes t2lesion load mancova controlled age disease duration individual followup time worse baseline performance information processing speed found patients higher edss followup m191 sd118 p0001 silent progression m219 sd101 p0038 conclusionperformance information processing speed might help identify patients risk physical impairment therefore neuropsychological assessment integrated clinical standard care support disease management pwms,0.0
tachycardia hypertension enhance tracer efflux spinal cord background disruption cerebrospinal fluid csf interstitial fluid isf exchange spinal cord likely contribute central nervous system cns diseases involve abnormal fluid accumulation including spinal cord oedema syringomyelia however physiological factors govern fluid transport spinal cord poorly understood aims study determine effects cardiac pulsations respiration tracer signal increase indicative molecular movement following infusion spinal cord grey white mattermethodsin sprague dawley rats physiological parameters manipulated effects spontaneous breathing generating alternating positive negative intrathoracic pressures mechanical ventilation positive intrathoracic pressure tachycardia heart atrial pacing well hypertension pharmacologically induced separately studied since fluid outflow spinal cord directly measured assessed molecular movement fluorescent ovalbumin afo647 visualised increase tracer signal following injection cervicothoracic spinal grey white matterresultstachycardia hypertension increased afo647 tracer efflux concomitant negative positive intrathoracic pressures generated spontaneous breathing compared positivepressure ventilated controls following afo647 tracer injection spinal grey matter increasing blood pressure heart rate resulted increased tracer movement away injection site compared hypotensive bradycardic animals hypertension p 005 tachycardia p 00001 similarly hypertension tachycardia produced greater movement afo647 tracer longitudinally along spinal cord following injection spinal white matter p 00001 p 0002 respectively tracer efflux strongly associated blood vessel typesconclusionsarterial pulsations profound effects spinal cord interstitial fluid homeostasis generating greater tracer efflux intrathoracic pressure changes occur respiratory cycle demonstrated increased craniocaudal csf tracer movement spinal cord parenchyma,0.0
creactive protein levels gadoliniumenhancing lesions associated degree depressive symptoms newly diagnosed multiple sclerosis front neurol 2021 oct 26 12719088 doi 103389 fneur2021719088 ecollection 2021abstractbackground inflammation essential pathogenesis multiple sclerosis ms immune system contribution development neurological symptoms intensively studied inflammatory biomarkers mental symptoms depression poorly understood context ms test depression correlates peripheral central inflammation markers ms patients soon diagnosis established methods fortyfour patients newly diagnosed relapsingremitting ms primary progressive ms clinically isolated syndrome age gender edss creactive protein crp albumin white blood cells count cerebrospinal fluid csf wbc presence gadolinium enhanced lesions ge t1weighted images total number typical ms lesion locations included linear regression models predict beck depression inventory bdi score depression dimension symptoms checklist 90revised scl90rd results crp elevation ge predicted significantly bdi crp p 0007 ge p 0019 scl90rd crp p 0004 ge p 0049 combination factors resulted pronounced depressive symptoms p 004 csf wbc edss well variables correlated depressive symptoms conclusions crp elevation ge associated depressive symptoms newly diagnosed ms patients markers can used identify ms patients exhibiting high risk development depressive symptoms early phases diseasepmid34764926 pmcpmc8575739 doi103389 fneur2021719088,0.0
identification solution drugrelated problems neurology unit tertiary hospital china background prevalence characteristics drugrelated problems drps factors associated occurrence drps neurology unit china remain unknown study aimed determine prevalence characteristics severity ratings drps identify factors associated occurrence drps neurology unit tertiary care academic teaching hospital chinamethodsa retrospective study drps pharmacists interventions neurology patients performed nonconsecutive 24month study period patient demographics clinical characteristics pharmacists intervention records collected characteristics severity ratings drps categorized using pharmaceutical care network europe pcne drp classification tool v900 national coordinating council medication error reporting prevention nccmerp classification respectivelyresultsa total 242 drps detected 974 admitted patients average 025 drps per patient treatment safety major type drps 106 438 followed treatment effectiveness 78 322 primary causes drps drug selection 124 441 dose selection 92 327 clinical pharmacists provided 525 interventions interventions occurred prescriber level 241 459 total 914 interventions accepted contributing solving 930 identified problems majority drps 210 868 rated severity categories b d causing patient harm multiple logistic regression showed creatinine clearance number medications used nasogastric feeding diabetes infectious diseases associated frequent drps p 005 conclusionsdrps relatively common neurology unit china primary causes drug dose selection clinical pharmacists can effectively reduce prevent drps optimize medication therapy,0.0
safety clinical effectiveness peginterferon beta1a relapsing multiple sclerosis realworld setting interim results plegridy observational program abstractbackgroundthe plegridy observational program pop ongoing 5year phase 4 realworld study safety effectiveness subcutaneous peginterferon beta1a patients relapsing multiple sclerosis rms methodsthis interim analysis pop assessed safety effectiveness peginterferon beta1a including subgroup analyses patients aged 50 50 years newly diagnosed nonnewly diagnosed patients new experienced peginterferon beta1a usersresultsa total 1208 patients enrolled pop mean standard deviation peginterferon treatment duration overall population 7570 5295 days overall incidence treatmentemergent adverse events aes 655 incidence higher new experienced peginterferon beta1a users 781 vs 524 overall incidence treatmentemergent serious aes 76 incidence lower younger older patients 58 vs 111 new unexpected safety signals reported overall treatment discontinuation due aes occurred 207 patients higher proportion new experienced peginterferon beta1a users 270 vs 142 discontinuing treatment due aes flulike symptoms injection site reactions significant predictors time treatment discontinuation adjusted annualized relapse rate arr 012 95 confidence interval 011013 overall population similar across subgroups overall population 4 years 791 patients relapse free estimated cumulative proportion patients confirmed disability worsening 18 67 patients achieved clinical evidence disease activity neda conclusionssafety data patients enrolled pop consistent established clinical safety profile peginterferon beta1a addition low arr high proportion patients achieving clinical neda 4 years across subgroups indicates effectiveness peginterferon beta1a treating rms realworld clinical settings,0.0
aberrant mitochondrial dynamics exacerbated response neuroinflammation novel mouse model cmt2a int j mol sci 2021 oct 26 22 21 11569 doi 103390 ijms222111569abstractcharcotmarietooth disease type 2a cmt2a common hereditary axonal neuropathy caused mutations mfn2 encoding mitofusin2 multifunctional protein located outer mitochondrial membrane order study effects novel mfn2k357t mutation associated early onset autosomal dominant severe cmt2a generated knockin mouse model mfn2k357t k357t mouse pups postnatally lethal mfn2+ k357t heterozygous mice asymptomatic histopathological changes sciatic nerves 10 months age however immunofluorescence analysis mfn2+ k357t mice revealed aberrant mitochondrial clustering sciatic nerves 6 months age optic nerves 8 months lumbar spinal cord white matter 10 months along microglia activation ultrastructural analyses confirmed dysmorphic mitochondrial aggregates sciatic optic nerves exposure 6monthold mice lipopolysaccharide mfn2+ k357t mice displayed higher immune response severe motor impairment increased cns inflammation microglia activation macrophage infiltrates overall ubiquitous mfn2k357t expression renders cns peripheral nerves mfn2+ k357t mice susceptible mitochondrial clustering augments response inflammation modeling cellular mechanisms may relevant development neuropathy patients cmt2apmid34769001 doi103390 ijms222111569,0.0
accuracy diagnostic indicators coeliac disease systematic review metaanalysis plos one 2021 oct 25 16 10 e0258501 doi 101371 journalpone0258501 ecollection 2021abstractbackground prevalence coeliac disease cd around 1 diagnosis challenged varied presentation nonspecific symptoms signs study aimed identify diagnostic indicators may help identify patients higher risk cd testing warrantedmethods international guidance systematic review methods followed review registered prospero crd42020170766 six databases searched april 2021 studies investigating diagnostic indicators symptoms risk conditions people without cd eligible inclusion risk bias assessed using quadas2 tool summary sensitivity specificity positive predictive values estimated diagnostic indicator fitting bivariate random effects metaanalysesfindings 191 studies reporting 26 diagnostic indicators included metaanalyses found large variation diagnostic accuracy estimates studies studies high risk bias found strong evidence people dermatitis herpetiformis migraine family history cd hla dq2 8 risk genotype anaemia type 1 diabetes osteoporosis chronic liver disease likely general population cd symptoms psoriasis epilepsy inflammatory bowel disease systemic lupus erythematosus fractures type 2 diabetes multiple sclerosis showed poor diagnostic ability sensitivity analysis revealed 3fold higher risk cd firstdegree relatives cd patientsconclusions targeted testing individuals dermatitis herpetiformis migraine family history cd hla dq2 8 risk genotype anaemia type 1 diabetes osteoporosis chronic liver disease improve casefinding cd therefore expediting appropriate treatment reducing adverse consequences migraine chronic liver disease yet included risk factor cd guidelines may appropriate added future research establish diagnostic value combining indicatorspmid34695139 doi101371 journalpone0258501,0.0
dyadic coping couples facing chronic physical illness systematic review front psychol 2021 oct 25 12722740 doi 103389 fpsyg2021722740 ecollection 2021abstractobjective chronic physical illness affects patients also partners dyadic coping dc ways couples cope dealing stressor chronic illnesshas received increased attention last three decades aim current study summarize state research dc couples chronic physical illnesses methods conducted systematic review qualitative quantitative mixedmethods studies published 1990 2020 assessing dc couples affected severe physical illnesses used dc related search terms literature search psycinfo psyndex medline five thousand three hundred thirty studies identified three electronic databases 49 included review 5 440 individuals reported 2 820 dyads excluded studies cancer cardiovascular disease multiple sclerosis existing reviews respective fields half studies included diabetes studies arthritis chronic obstructive pulmonary disease copd cystic fibrosis human immunodeficiency virus hiv huntingtons disease lupus erythematosus parkinsons disease renal diseases stroke endometriosis two raters extracted data using predefined protocol including study quality results collated narrative synthesis organized illness dc operationalization results overall dc associated beneficial outcomes physical health wellbeing relationship satisfaction differential effects became apparent certain chronic conditions potentially depending certain disease characteristics earlyonset suddenonset lifethreatening conditions conclusion facing challenges together couple seemed indispensable adapting diverse range demands related chronic illnesses specific demands particular chronic diseases need development truly dyadic interventions eye specific challenges various chronic conditionspmid34759866 pmcpmc8573212 doi103389 fpsyg2021722740,0.0
csf findings acute nmdar lgi1 antibodyassociated autoimmune encephalitis neurol neuroimmunol neuroinflamm 2021 oct 25 8 6 e1086 doi 101212 nxi0000000000001086 print 2021 novabstractbackground objectives csf antibodydefined autoimmune encephalitis ae subtypes shows subtypedependent degrees inflammation ranging rare often mild frequent often robust aes nmda receptor antibodies nmdare leucinerich gliomainactivated protein 1 antibodies lgi1e represent opposite ends spectrum nmdare typically frequent robust lgi1e rare mild csf inflammation indepth analysis characterized csf findings acute therapynaive nmdare lgi1e multicentric retrospective crosssectional settingmethods eightytwo patients nmdare 36 patients lgi1e german network research autoimmune encephalitis generate lumbar puncture within 90 days onset immunotherapy included csf parameters comprised leukocytes oligoclonal bands ocbs csf serum ratios albumin immunoglobulin g igg iga m igm latter 3 converted z scores according reiber formulas mrz reaction tested 14 patients nmdare 6 patients lgi1e respectivelyresults csf abnormal 94 nmdare 36 lgi1e patients robust quantitative intrathecal immunoglobulin synthesis iis igg igm iga characteristic nmdare absent lgie nmdare csf leukocytes higher iis present pronounced addition nmdare csf leukocytes lower iis occurred less often lesser degree older age patients nmdare severe functional impairment often positive ocbs csf obtained later 3 weeks onset leukocytes lower parallel correlation leukocytes iis disappeared iis partially independent disease duration mrz reaction positive 5 36 patients nmdare associations completely absent lgi1e younger patients showed bloodcsf barrier dysfunction lgi1e nmdare bloodcsf barrier dysfunctional csf leukocytes higherdiscussion nmdare lgie differ typical extent csf inflammation addition patterns formed different inflammatory csf parameters relationship disease severity age disease duration subtypecharacteristic moreover signs multiple sclerosislike chronic inflammation present subgroup patients nmdare csf patterns might markers different immunopathogeneses lgi1e nmdarepmid34697224 doi101212 nxi0000000000001086,0.0
phenotypic spectrum genetics pax2related disorder chinese cohort background pathogenic variants pax2 cause autosomaldominant pax2related disorder includes variable phenotypes ranging renal coloboma syndrome rcs congenital anomalies kidney urinary tract cakut nephrosis phenotypic variability makes difficult define phenotypic spectrum associated genotypemethodswe collected phenotypes patients enrolled china national multicenter registry diagnosed pathogenic variant pax2 reviewed published cases pax2related disorders conducted phenotypebased cluster analysis variant types molecular modeling structural impact missense variantsresultstwenty different pax2 pathogenic variants identified 32 individuals 27 families diagnosis rcs 9 cakut 11 nephrosis 12 chinese cohort individuals abnormal kidney structure rcs cakut group tended likely presumed gene disruptive lgd variants fisher test p 005 system review 234 reported cases date indicated clear association rcs heterozygous lossoffunction pax2 variants lgd variants furthermore identified subset pax2 missense variants dnabinding domain predicted affect protein structure proteindna interaction associated phenotype rcsconclusiondefining phenotypic spectrum combined genotype pax2related disorder allows us predict pathogenic variants associated renal ophthalmological development highlighted approach structurebased analysis can applied diagnostic strategy aiding precise timely diagnosis,0.0
multiple sclerosis following sarscov2 infection case report literature review cureus 2021 oct 25 13 10 e19036 doi 107759 cureus19036 ecollection 2021 octabstractcoronavirus disease 19 covid19 caused severe acute respiratory coronavirus 2 sarscov2 apart respiratory manifestations covid19 can affect nervous system due neurotropic features neurological manifestations complications include headache polyneuropathies cerebrovascular accidents seizures encephalopathy demyelinating disease describe case multiple sclerosis demyelinating disease following covid19 infection rarely reported literature 47yearold female presented fatigue blurry vision numbness signs upper motor neuron lesions occurred three weeks covid19 infection magnetic resonance imaging brain revealed demyelinating lesions periventricular area hemispheres suggesting demyelinating disease provisional diagnosis multiple sclerosis made condition improved commencement methylprednisolonepmid34858736 pmcpmc8612412 doi107759 cureus19036,1.0
seasonal variability serum 25hydroxyvitamin d multiple sclerosis onset sci rep 2021 oct 25 11 1 20989 doi 101038 s41598021003440abstractvitamin d deficiency associated increased risk multiple sclerosis ms however effect age disease onset remains unclear study examines relationship serum 25hydroxyvitamin d 25 oh d levels age first symptom onset among recently diagnosed ms patients serum 25 oh d measured forty ms patients sampled near disease onset correcting seasonal variability association 25 oh d levels along clinical measures igg index age ms onset examined using multivariable linear regression serum 25 oh d correlated age onset p 05 observed bias among previously reported associations 25 oh d ms disease measures resulting nonrandom distribution sampling season correcting seasonal 25 oh d clinical measures csf igg index remained significantly associated age disease onset 535 p 0028 summary observed association age onset serum 25 oh d levels observed negative correlation csf igg index although will require investigationpmid34697348 doi101038 s41598021003440,0.0
equine vitiligolike depigmentation grey horses related genes involved immune response tumor metastasis background horses autoimmune disease vitiligo characterized loss melanocytes results patchy depigmentation skin around eyes muzzle perianal region vitiligolike depigmentation occurs predominantly horses displaying grey coat colour observed prevalence level 260670 grey horses compared 0835 nongrey horses polygenetic background complex disease well documented humans underlying candidate genes skin disorder horses remain unknown study aim perform genomewide association study gwas identifying putative candidate loci vitiligolike depigmentation horsesmethodsin current study performed gwas analysis using highdensity 670 k single nucleotide polymorphism snp data 152 lipizzan 104 noriker horses phenotyped vitiligolike depigmentation visual inspection quality control 376 219 snps remained analyses genomewide bonferroni corrected significance level p 133e7resultswe identified seven candidate genes four chromosomes eca1 eca13 eca17 eca20 putatively involved vitiligo pathogenesis grey horses highlighted genes phf11 setdb2 carhsp1 litafd associated innate immune system genes rcbtb1 litafd nubpl ptp4a1 play role tumor suppression metastasis antagonistic pathogenesis vitiligo relation cancer specific enhanced cell motility metastasis typical melanoma predilection sites underlines plausible involvement rcbtb1 litafd nubpl ptp4a1conclusionsthe proposed candidate genes equine vitiligolike depigmentation indicate antagonistic relation vitiligo tumor metastasis horse population higher incidence melanoma replication expression studies lead better understanding skin disorder horses,0.0
pediatriconset multiple sclerosis poland registrybased retrospective cohort study abstractbackground epidemiologic data pediatriconset multiple sclerosis poms central eastern europe limited aim study determine incidence prevalence clinical features poms polandmethods registrybased retrospective study conducted among polish children population age 18 years 1 january 2010 31 december 2019 total 329 pediatric juvenile patients fulfilled international pediatric ms study group ipmssg criteria ms reported polish multiple sclerosis registry considered estimation age sexspecific prevalence per 100 000 persons incidence rates per 100 000 personyears demographic data clinical presentation treatment strategies also investigatedresults december 31 2019 database collected data 329 patients 18 years poms diagnosis 101 boys 228 girls mean age 153 38 years ageadjusted prevalence standardized european standard population 519 100 000 95 confidence interval ci 464578 significantly higher prevalence recorded girls 741 95 ci 648844 boys 308 95 ci 250374 p0001 mean annual standardized incidence poland 2015 2019 077 95ci 045102 per 100 000 personyears highest overall standardized incidence 106 95ci 082134 noted 2018 patients 957 relapsingremitting disease polysymptomatic onset onethirds cases 823 treated diseasemodifying drugs family history ms reported 26 cases 79 conclusion first report registrybased study poland increasing prevalence incidence poms found last years temporal trend corroborate findings studies conducted elsewhere,0.0
diverse inflammatory threats modulate astrocytes ca2+ signaling via connexin43 hemichannels organotypic spinal slices abstractneuroinflammation escalation factor shared vast range central nervous system cns pathologies neurodegenerative diseases neuropsychiatric disorders cns immune status emerges integration responses resident resident cells leading alterations neural circuits functions explore spinal cord astrocyte reactivity inflammatory threats focused study effects local inflammation controlled microenvironment organotypic spinal slices developed spinal cord mouse embryos organ cultures represent complex vitro model sensorymotor cytoarchitecture synaptic properties spinal cord resident cells retained 3d fashion recently exploit cultures model two diverse immune conditions cns involving different inflammatory networks products specifically focus tuning calcium signaling astrocytes diverse types inflammation investigate mechanisms modulate intracellular calcium release spreading among astrocytes inflamed environment organotypic spinal cord slices cultured two three weeks vitro wiv exposed 6 h cocktail cytokines cks composed tumor necrosis factor alpha tnf interleukin1 beta il1 granulocyte macrophagecolony stimulating factor gmcsf lipopolysaccharide lps live calcium imaging ventral horn document increase active astrocytes occurrence spontaneous calcium oscillations displayed cells exposed inflammatory threat several pharmacological treatments demonstrate intracellular calcium sources activation connexin 43 cx43 hemichannels pivotal role increasing calcium intercellular communication cks lps conditions cx43 gap junction communication apparently reduced inflammatory treatments,0.0
role nutritional lifestyle physical activity multiple sclerosis pathogenesis management narrative review nutrients 2021 oct 25 13 11 3774 doi 103390 nu13113774abstractstudies role nutritional factors physical activity pa pathogenesis multiple sclerosis ms go back long time despite intrinsic difficulty studying positive negative role ms interest researchers topics increased last decades since role diet investigated perspective association diseasemodifying drugs dmd association dmd diets pa might additive effect modifying disease severity among various diets investigated lowcarbohydrate glutenfree mediterranean lowfat fastingmimicking western diets lowcarbohydrate mediterranean fastmimicking diets shown animal models humans positive effect ms course patientreported outcomes pros however mediterranean diet easier maintained compared fastmimicking lowcarbohydrate diets may lead detrimental side effects requiring careful clinical monitoring conversely western diet characterized high intake highly saturated fats carbohydrates may lead activation proinflammatory immune pathways therefore recommended pa showed positive effect animal models well disease course pros humans training combined exercises considered effective approachpmid34836032 doi103390 nu13113774,0.0
safety natalizumab reinfusion multiple sclerosis patients active sarscov2 infection summarycovid19 pandemic represented challenge management treatments multiple sclerosis ms natalizumab ntz ntz interferes homing lymphocytes central nervous system reducing immune surveillance opportunistic infection although ntz efficacy starts decline 8 weeks last infusion increasing risk disease reactivation evidence lacking safety reinfusion active sarscov2 infection report clinical outcomes 18 pwms receiving ntz retreatment confirmed sarscov2 infection worsening infection recovery delay observed data supports safety ntz redosing circumstances,0.0
advancing motor rehabilitation adults chronic neurological conditions increased involvement kinesiologists perspective review abstractmany people neurological conditions experience challenges movement although rehabilitation often provided acutely subacutely following onset condition motor deficits commonly persist longterm exacerbated disuse inactivity notably motor rehabilitation approaches incorporate exercise physical activity can support gains motor function even chronic stages many neurological conditions however delivering motor rehabilitation longterm basis people chronic neurological conditions challenge within health care systems onus often placed patients find pay services neurological motor rehabilitation largely domain physical occupational therapists kinesiologists may able complement existing care support delivery longterm neurological motor rehabilitation specifically provision supported exercise physical activity programs perspective style review article discuss potential contributions kinesiologists advancing field exercise programming focusing communitybased interventions increase physical activity levels conclude recommendations kinesiologists role might optimized towards improving longterm outcomes people chronic neurological conditions considering issues related professional regulation models care,0.0
predictors neutralizing antibody response bnt162b2 vaccination allogeneic hematopoietic stem cell transplant recipients background factors affecting response sarscov2 mrna vaccine allogeneic hematopoietic stem cell transplantation allohct recipients remain elucidatedmethodsforty allohct recipients included study immunization bnt162b2 mrna vaccine days 0 21 binding antibodies ab sarscov2 receptor binding domain rbd assessed days 0 21 28 49 neutralizing ab sarscov2 wild type nt50 assessed days 0 49 results observed allohct patients compared obtained 40 healthy adults naive sarscov2 infection flow cytometry analysis peripheral blood cells performed vaccination identify potential predictors ab responsesresultsthree patients detectable antirbd ab vaccination among 37 sarscov2 naive patients 20 54 32 86 patients detectable antirbd ab 21 days 49 days postvaccination comparing antirbd ab levels allohct recipients healthy adults observed significantly lower antirbd ab levels allohct recipients days 21 28 49 49 allohct patients versus 88 healthy adults detectable nt50 ab day 49 allohct recipients significantly lower nt50 ab titers healthy adults p 00004 ongoing moderate severe chronic gvhd p 001 well rituximab administration year prior vaccination p 005 correlated low antirbd nt50 ab titers 49 days first vaccination multivariate analyses compared healthy adults allohct patients without chronic gvhd rituximab therapy comparable antirbd ab levels nt50 ab titers day 49 flow cytometry analyses vaccination indicated ab responses allohct patients strongly correlated number memory b cells naive cd4+ t cells r 05 p 001 weakly number follicular helper t cells r 04 p 001 conclusionschronic gvhd rituximab administration allohct recipients associated reduced ab responses bnt162b2 vaccination immunological markers help identify allohct patients risk poor ab response mrna vaccination trial registration study registered clinicaltrialsregistereu 11 march 2021 eudractct # 202100067383,0.0
neuropathology sca34 showing widespread oligodendroglial pathology vacuolar white matter degeneration case study abstractspinocerebellar ataxia type 34 sca34 autosomal dominant inherited ataxia due mutations elovl4 encodes one longchain fatty acid elongases sca38 another spinocerebellar ataxia caused mutations elovl5 gene encoding another elongase however previous studies describing neuropathology either sca34 38 report describes neuropathological findings 83yearold man sca34 carrying pathological elovl4 mutation nm_022726 c736tg pw246g macroscopic findings include atrophies pontine base cerebellum cerebral cortices microscopically marked neuronal pontocerebellar fiber loss observed pontine base addition pontine base accumulation cd68positive macrophages laden periodic acidschiff pas positive material observed many vacuolar lesions found white matter cerebral hemispheres lesser extent brainstem spinal cord white matter immunohistological examination ultrastructural observations electron microscope suggest vacuolar lesions remnants degenerated oligodendrocytes electron microscopy also revealed myelin sheath destruction unexpectedly aggregation fourrepeat tau observed spatial pattern reminiscent progressive supranuclear palsy tau lesions included glial fibrillary tangles resembling tuftshaped astrocytes neurofibrillary tangles pretangles first report illustrate heterozygous missense mutation elovl4 leads neuronal loss accompanied macrophages laden paspositive material pontine base oligodendroglial degeneration leading widespread vacuoles white matter sca34,1.0
development therapies rare genetic disorders gpx4 roadmap opportunities background extremely rare progressive diseases like sedaghatiantype spondylometaphyseal dysplasia ssmd can neonatally lethal therefore go undiagnosed difficult treat recent sequencing efforts linked disease mutations gpx4 consequences resulting enzyme glutathione peroxidase 4 offers potential diagnostic therapeutic avenues suffering disease though steps toward treatments often convoluted expensive timeconsumingmain bodythe curegpx4 organization developed promote awareness gpx4related diseases like ssmd well support research lead essential therapeutics patients provide overview 21 published ssmd cases compiled additional sequencing data four previously unpublished individuals illustrate genetic component ssmd role sequencing data diagnosis outline detail steps curegpx4 taken reach milestones team creation disease understanding drug repurposing design future studiesconclusionthe primary aim review provide roadmap therapy development rare ultrarare difficult diagnose diseases well increase awareness genetic component ssmd work will offer better understanding gpx4related diseases help guide researchers clinicians patients interested rare diseases find path towards treatments,0.0
air pollution risk factor multiple sclerosis commentary n,0.0
air pollution risk factor multiple sclerosis yes n,0.0
effect cladribine covid19 serology responses following two doses bnt162b2 mrna vaccine patients multiple sclerosis abstractbackgroundmultiple sclerosis ms patients treated immunomodulatory treatments can influence ability develop protective antibody response sarscov2 vaccinevaccine efficacy important treatment decision patientsnull reassurancethe main objective assess antibody response sarscov2 vaccine ms patients treated cladribinemethodsserology response tested 97 participants 67 ms patients 30 healthy controls hcs using two independent methods 23 weeks following second dose bnt162b2 vaccineresultshcs n30 ms patients treated cladribine n32 100 positive serology response sarscov2 spike protein following second vaccine dose mean s1 s2igg rbdigg28451049 130419411 au ml 22631214 1055411405 au ml respectively comparable findings observed untreated ms patients interferon beta1atreated ms patients mean s1 s2igg 28211001 27699431 au ml respectively correlation found lymphocyte counts treatment duration time cladribine dose vaccination serology response antibody titersconclusion relevancecladribine treated ms patients able produce antibodies sarscov2 mrna vaccine era covid19 pandemic reassuring important patients physicians will allow develop consensus guidelines,0.0
air pollution risk factor multiple sclerosis n,0.0
temporal trends multiple sclerosis disease activity electronic health records indicators abstractbackgroundlongterm data multiple sclerosis ms inflammatory disease activity limited examined electronic health records ehr indicators disease activity people msmethodswe analyzed prospectively collected research registry data linked ehr data clinicbased cohort 2000 2016 used trend yearly incident relapse rate registry data benchmark calculated temporal trends potentially relevant ehr measures including mean count ms diagnostic code mentions msrelated concepts msrelated health utilizations selected prescriptionsresults1 555 ms patients registry ehr data 2000 2016 registry data showed declining trend yearly incident relapse rate parallel increasing trend dmt usage among ehr measures covariateadjusted frequency diagnostic code ms procedure codes msrelated imaging studies emergency room visits electronic prescription steroids declined time mirroring temporal trend benchmark yearly incident relapse rateconclusionthis study highlights ehr indicators ms relapse enable largescale examination longterm disease activities inform individual patient monitoring clinical settings ehr data available,0.0
clinical trials amyotrophic lateral sclerosis systematic review perspective brain commun 2021 oct 23 3 4 fcab242 doi 101093 braincomms fcab242 ecollection 2021abstractamyotrophic lateral sclerosis progressive devastating neurodegenerative disease despite decades clinical trials effective diseasemodifying drugs remain scarce understand challenges trial design delivery performed systematic review phase ii phase ii iii phase iii amyotrophic lateral sclerosis clinical drug trials trial registries pubmed 2008 2019 identified 125 trials investigating 76 drugs recruiting 15 000 people amyotrophic lateral sclerosis 90 trials used traditional fixed designs limitations understanding disease biology outcome measures resources barriers trial participation rapidly progressive disabling heterogenous disease hindered timely definitive evaluation drugs twoarm trials innovative trial designs especially adaptive platform trials may offer significant efficiency gains end propose flexible scalable multiarm multistage trial platform opportunities participate clinical trial can become default people amyotrophic lateral sclerosispmid34901853 pmcpmc8659356 doi101093 braincomms fcab242,0.0
case report multiple sclerosis relapses vaccination sarscov2 series clinical cases front neurol 2021 oct 22 12765954 doi 103389 fneur2021765954 ecollection 2021abstractobjective describe temporal association covid19 vaccine administration multiple sclerosis ms relapses methods case series study collected four ms centres central italy using data 16 ms patients received covid19 vaccination presented clinically radiologically confirmed relapses march june 2021 collected patients relevant medical history including demographics ms clinical course diseasemodifying treatment dmt received applicable data mri scans obtained covid19 vaccination results three 16 patients received diagnosis ms first episode occurring covid19 vaccination 13 already diagnosis ms among 9 treatment dmts ten patients received bnt162b2 pfizerbiontech 2 patients mrna1273 moderna 4 patients chadox1 ncov19 astrazeneca ms relapses occurred 3 days 3 weeks receiving first dose covid19 vaccination booster patients evidence radiological activity mri discussion clinical radiological findings cohort ms patients confirmed disease re activation suggested temporal association disease activity covid19 vaccination nature temporal association whether causative incidental remains establishedpmid34744992 pmcpmc8569136 doi103389 fneur2021765954,0.0
evaluating effects glatiramer acetate treatment amyloid deposition tau phosphorylation 3xtg mouse model alzheimer#39 s disease front neurosci 2021 oct 22 15758677 doi 103389 fnins2021758677 ecollection 2021abstractneuroinflammation driven accumulation amyloid can lead neurofibrillary tangle formation alzheimers disease ad test hypothesis antiinflammatory immunomodulatory agent might beneficial effects amyloid tau pathology well microglial phenotype evaluated glatiramer acetate ga multiple sclerosis drug thought bias type 2 helper t th2 cell responses alternatively activate myeloid cells administered weekly subcutaneous injections ga pbs 15monthold 3xtg ad mice develop amyloid tau pathology period 8 weeks found subcutaneous administration ga improved behavioral performance novel object recognition decreased plaque 3xtg ad mice changes tau phosphorylation mixed specific changes phosphoepitopes seen immunohistochemistry observed western blot addition found trend toward increased microglia complexity 3xtg mice treated ga suggesting shift toward homeostasis findings correlated subtle changes microglial transcriptome striking difference upregulation dcstamp lastly found evidence changes proportions major helper t cell th subtypes periphery overall study provides evidence benefits immunomodulatory therapies alter adaptive immune system goal modifying microglia responses treatment alzheimers diseasepmid34744620 pmcpmc8569891 doi103389 fnins2021758677,0.0
effect emotional freedom technique fatigue among women multiple sclerosis randomized controlled trial iran j nurs midwifery res 2021 oct 22 26 6 531536 doi 104103 ijnmrijnmr_188_19 ecollection 2021 novdecabstractbackground study aimed investigate effect emotional freedom technique eft severity fatigue among women multiple sclerosis ms materials methods singleblind randomized controlled trial study conducted 50 women ms isfahan iran sampling performed using simple sampling method participants randomly divided two groups case sham using minimization method eft intervention performed case group 2 sessions per week 4weeks period sham group psychological part eft technique like case group mild tapping applied false points period time fatigue severity score obtained using fatigue severity scale fss immediately 4 weeks intervention two groups data analysis conducted using descriptive inferential statistical methodsresults results independent ttest indicated mean sd score fatigue severity intervention significantly different case sham groups 548 075 539 071 p 067 however difference significant immediately 305 089 515 094 4 weeks intervention 310 081 559 057 p 0001 conclusions seems eft effective diminishing fatigue among patients ms recommended convenient safe nonmedicament strategy selfmanagement fatigue among patients can used bedside nursespmid34900653 pmcpmc8607895 doi104103 ijnmrijnmr_188_19,0.0
ideas initiative pilot study assess impact rare diseases patients healthcare systems background rare diseases rd diverse collection 710 000 different disorders affect small number people per disease rarity fragmentation patients across thousands different disorders medical needs rd patients well recognized quantified healthcare systems hcs methodologywe performed pilot ideas study attempted quantify number rd patients direct medical costs 14 representative rd within 4 different hcs databases performed preliminary analysis diagnostic journey selected rd patientsresultsthe overall findings notable 1 rd patients difficult quantify hcs using icd coding search criteria likely results undercounting underestimation true impact hcs 2 per patient direct medical costs rd high estimated around threefivefold higher agematched controls 3 preliminary evidence shows diagnostic journeys likely prolonged many patients may result progressive irreversible costly complications diseaseconclusionsthe results small pilot suggest rd high medical burdens patients hcs collectively represent major impact public health machinelearning strategies applied hcs databases medical records using sentinel disease patient characteristics may hold promise faster accurate diagnosis many rd patients explored help address high unmet medical needs rd patients,0.0
distribution trunk impairments relationship disability level individuals multiple sclerosis abstractbackgroundtrunk control essential movement balance walking ignored regular medical followupobjectivefirst describe distribution trunk impairments full range disability levels individuals ms second identify relationship trunk control measured trunk impairment scale tis 20 general disability measured expanded disability status scale edss methods154 individuals ms included mean age 536 sd 1106 edss ranging 10 85 mean 447 sd 255 relationship edss tis 20 calculated spearman correlation coefficient total sample subgroups edss 4 versus edss 45resultstrunk impairments detected throughout full range disability including individuals low disability pelvic elevation lower trunk rotation appeared difficult perform total sample moderate correlation found rho 608 disability edss trunk performance tis 20 subanalyses revealed poor correlation rho 193 edss 4 subgroup strong correlation edss 45 subgroup rho 712 conclusionthe results advocate including trunk assessment already early disease stages ms particularly pelvic elevation trunk rotation dedicated rehabilitation strategies,0.0
performance plasma a42#x2f a40 ratio measured novel hplcms#x2f ms method biomarker amyloid pet status dpukkorean cohort background assessed feasibility plasma a42 a40 determined using novel liquid chromatographymass spectrometry method lcms useful biomarker pet status korean cohort dpuk studymethodsa total 580 participants belonging six groups alzheimers disease dementia add n 134 amnestic mild cognitive impairment amci n 212 old controls oc n 149 young controls yc n 15 subcortical vascular cognitive impairment svci n 58 cerebral amyloid angiopathy caa n 12 included study plasma a40 a42 quantitated using new antibodyfree lcms drastically reduced sample preparation time cost performed receiver operating characteristic roc analysis develop cutoff a42 a40 investigated performance predicting centiloidbased pet positivity pet+ resultsplasma a42 a40 lower pet+ individuals add amci oc svci p 0001 caa p 0133 group yc oc amci add groups plasma a42 a40 predicted pet+ area roc curve auc 0814 cutoff 02576 adding age apoe4 diagnosis auc significantly improved 0912conclusionplasma a42 a40 measured novel lcms method showed good discriminating performance based pet positivity,0.0
classification neurological diseases using multidimensional cerebrospinal fluid analysis brain 2021 apr 12awab147 doi 101093 brain awab147 online ahead printabstractalthough cerebrospinal fluid csf analysis routinely enables diagnosis neurological diseases mainly used gross distinction infectious autoimmune inflammatory degenerative central nervous system cns disorders investigate whether multidimensional cellular blood csf characterization can support diagnosis clinically similar neurological diseases analyzed 546 patients autoimmune neuroinflammatory degenerative vascular conditions crosssectional retrospective study combining feature selection dimensionality reduction machine learning approaches identified pandisease parameters altered across autoimmune neuroinflammatory cnsdiseases differentiating neurological conditions interautoimmunity classifiers subdifferentiating variants cnsdirected autoimmunity pandisease well diseasesspecific changes formed continuum reflecting clinical disease evolution validation cohort 231 independent patients confirmed combining multiple parameters composite scores can assist classification neurological patients overall show integrated analysis blood csf parameters improves differential diagnosis neurological diseases thereby facilitating early treatment decisionspmid33848319 doi101093 brain awab147,0.0
ccl4 induces inflammatory signalling barrier disruption neurovascular endothelium brain behav immun health 2021 oct 22 18100370 doi 101016 jbbih2021100370 ecollection 2021 decabstractbackground neuroinflammation many chemokines alter function bloodbrain barrier bbb regulates entry macromolecules immune cells brain milieu brain altered biochemical structural changes contribute pathogenesis neuroinflammation may impact neurogenesis chemokine ccl4 previously known mip1 upregulated wide variety central nervous system disorders including multiple sclerosis thought play key role neuroinflammatory process however effect ccl4 bbb endothelial cells ecs unknownmaterials methods expression distribution ccr5 phosphorylated p38 factin zonula occludens1 zo1 vascular endothelial cadherin vecadherin analysed human bbb ec line hcmec d3 western blot immunofluorescence presence absence ccl4 barrier modulation response ccl4 using hcmec d3 monolayers assessed measuring molecular flux 70 kda ritcdextran transendothelial lymphocyte migration permeability changes response ccl4 vivo measured occlusion technique pial microvessels wistar rats fluorescein angiography mouse retinaeresults ccr5 receptor ccl4 expressed hcmec d3 cells ccl4 stimulation led phosphorylation p38 formation actin stress fibres indicative intracellular chemokine signalling distribution junctional proteins also altered response ccl4 junctional zo1 reduced circa 60 within 60 min addition surface vecadherin redistributed internalisation consistent changes ccl4 induced hyperpermeability vitro vivo increased transmigration lymphocytes across monolayers hcmec d3 cellsconclusion results show ccl4 can modify bbb function may contribute disease pathogenesispmid34755124 pmcpmc8560974 doi101016 jbbih2021100370,0.0
tspo pet imaging natalizumabassociated progressive multifocal leukoencephalopathy brain 2021 mar 23awab127 doi 101093 brain awab127 online ahead printabstractprogressive multifocal leukoencephalopathy pml severe infection central nervous system caused polyomavirus jc jcv can occur multiple sclerosis ms patients treated natalizumab clinical management patients natalizumabassociated pml challenging least current imaging tools early detection longitudinal monitoring differential diagnosis pml lesions limited evaluate whether tspo positron emission tomography pet imaging can applied monitor inflammatory activity pml lesions time differentiate ms lesions monocenter pilot study followed 8 patients natalizumabassociated pml pet imaging using tspo radioligand 18f ge180 combined frequent 3 t mri imaging addition compared tspo pet signals pml lesions signal pattern ms lesions 17 independent ms patients evaluated standardized uptake value ratio suvr well morphometry tspo uptake putative pml ms lesions areas compared radiologically unaffected pseudoreference region cerebrum furthermore tspo expression situ immunohistochemically verified determining density cellular identity tspoexpressing cells brain sections four patients early natalizumabassociated pml well five patients forms pml six patients inflammatory demyelinating cns lesions clinically isolated syndrome ms histological analysis revealed reticular accumulation tspo expressing phagocytes pml lesions phagocytes showed homogenous distribution putative ms lesions tspo pet imaging showed enhanced tracer uptake natalizumabassociated pml lesions present early chronic stages 52 months pml diagnosis gadolinium enhancement mri rapidly declined baseline levels tspo tracer uptake followed slow one phase decay curve tspobased 3dimensional diagnostic matrix taking account uptake levels well shape texture tspo signal differentiated 96 pml ms lesions indeed treatment rituximab natalizumabassociated pml three patients affect tracer uptake assigned pml lesions reverted tracer uptake baseline assigned active ms lesions taken together study suggests tspo pet imaging can reveal cns inflammation natalizumabassociated pml tspo pet may facilitate longitudinal monitoring disease activity help distinguish recurrent ms activity pml progressionpmid33757118 doi101093 brain awab127,1.0
patients experiences multiple sclerosis diseasemodifying therapies daily life qualitative interview study background besides coping disease many uncertainties people relapsingremitting multiple sclerosis face complex decisions concerning diseasemodifying therapies dmts interview study aimed assess patients experiences dmtsmethodsproblemcentred interviews conducted 50 people relapsingremitting multiple sclerosis germany using maximum variation sampling covering licensed dmts data analysed thematically using deductive inductive categoriesresults47 50 patients treatment least one approved dmts main themes 1 starting dmt 2 switching another dmt 3 discontinuing dmt 4 multiple sclerosis without starting dmt different intercorrelated factors influenced decisionmaking processes dmt individual experiences dmts daily life contained effort administration success failure dmts coping strategies wellbeing without dmts decisionmaking process dmt use treatments can understood constant continually shifting process complicated different factors change time experiences dmts characterized attempts handle uncertainty re gain control integrate adaptivity ones lifeconclusionsthe study provides rich nuanced amount patients experiences dmts findings demonstrate importance practitioners look current life circumstances patients multiple sclerosis recommending dmt promote enable patients make informed decisions,0.0
potential application maraviroc therapy neuropathic pain pol merkur lekarski 2021 oct 22 49 293 379381abstractaccording international association study pain iasp neuropathic pain defined pain caused lesion disease somatosensory nervous system general population 78 adults suffer chronic pain neuropathic characteristic common causes include lumbar radiculopathy postherpetic neuropathy hiv infection autoimmune diseases multiple sclerosis metabolic diseases diabetic neuropathy stroke spinal cord injury current pharmacotherapy neuropathic pain insufficient effectiveness comprehension neuropathic pain mechanism necessary research new therapeutic methods study verify analgesic effect maraviroc antagonist chemokine receptor ccr5 potential role treatment neuropathic pain study focused dependency opioid chemokine receptors similar structure receptors occurs crossdesensitization phenomenon chemokine antagonist maraviroc belongs group entry inhibitors antiretroviral drug enhances analgesic properties opioids inhibition crossdesensitization opioids receptor application maraviroc morphine can reduce effective dosage morphine 2 3 fold moreover research show prophylactic administration maraviroc without opioid analgesics suppresses development neuropathic pain symptoms influence glial phenotype decreases secretion proinflammatory cytokines increases antiinflammatory cytokine secretion furthermore decreases expression chemikine receptor mrna chemikine ligands secreted microglia astrocytes result nerve injury conclude maraviroc immunomodulatory properties potentiates opioid analgesics effect can used neuropathic pain therapy potential coanalgesicpmid34800029,0.0
type ii diabetes mellitus amyotrophic lateral sclerosis genetic overlap causality mediation j clin endocrinol metab 2021 jun 25dgab465 doi 101210 clinem dgab465 online ahead printabstractobjective disentangle nature inverse relationship type ii diabetes t2d mellitus amyotrophic lateral sclerosis als methods depending summary statistics t2d n898 130 als n80 610 estimated genetic correlation prioritized pleiotropic genes multipletissue eqtl weighted integrative analysis ccfdr method implemented mendelian randomization mr analyses evaluate causal relationship two diseases mediation analysis performed assess mediating role t2d pathway t2drelated glycemic anthropometric traits alsresults found supportive evidence common genetic foundation t2d als rg0223 p0004 identified eight pleiotropic genes ccfdr010 mr analysis confirmed t2d exhibited neuroprotective effect als leading approximately 5 95 confidence intervals 096 p0038 reduction disease risk contrast substantial evidence observed supported causal influence als t2d mediation analysis revealed t2d can also serve active mediator several glycemic anthropometric traits including highdensity lipoprotein cholesterol overweight body mass index obesity class 1 obesity class 2 mediation effect estimated 0024 0022 0041 0016 0012 respectivelyconclusion provided new evidence supporting observed inverse link t2d als revealed shared genetic component causal association commonly drove relationship also demonstrated mediating role t2d standing pathway t2drelated glycemic anthropometric traits alspmid34171091 doi101210 clinem dgab465,1.0
impact lockdown covid19 pandemic central activation muscle activity contractile function spasticity people multiple sclerosis biomed res int 2021 oct 21 20212624860 doi 101155 2021 2624860 ecollection 2021abstractbackground people multiple sclerosis ms suffer symptoms related neural control reduced central activation lower muscle activity accentuated spasticity forced 9week home confinement related covid19 spain may worsened symptoms however study demonstrated impact home confinement neuromuscular mechanisms ms population study aimed analyzing effects 9week home confinement central activation muscle activity contractile function spasticity ms patientsmethods eighteen participants enrolled study left right knee extensor maximum voluntary isometric contraction mvic maximal neural drive via peak surface electromyography emg vastus lateralis central activation ratio car muscle contractile function via electrical stimulation knee extensor muscles well spasticity using pendulum test measured immediately home confinementresults seventeen participants completed study car significantly decreased lockdown es 1271 p 0001 regarding spasticity trend decrease number oscillations es 0511 p 0059 significant decrease duration oscillations es 0568 p 0038 furthermore left leg significant decrease first swing excursion es 0612 p 0027 relaxation index es 0992 p 0001 muscle contractile properties mvic emg variables modified confinementconclusions results suggest home confinement period 9 weeks may lead increase lower limb spasticity greater deficit voluntary activation knee extensorspmid34692828 pmcpmc8531768 doi101155 2021 2624860,0.0
physicians experiences attitudes beliefs towards medical cannabis systematic literature review background increasing number countries legalise use medical cannabis allow narrow range medical conditions physicians often patients general practitioner play major role implementing policy many however perceive lack evidencebased knowledge confident providing patients medical cannabis objectives review synthesise findings hospital physicians gps experiences attitudes beliefs towards use medical cannabis purpose identifying barriers facilitators towards providing patientsmethodspeerreviewed articles addressing hospital physicians gps experiences attitudes beliefs towards use medical cannabis searched systematically pubmed scopus embase cochrane libraryresultstwentyone articles included five different countries medical cannabis laws varied studied physicians experienced frequent inquiries medical cannabis patients 4995 10 95 physicians willing prescribe provide patients depending setting specialty experience among physicians review found physicians experienced prescribing medical cannabis convinced benefits less worried adverse effects nonexperienced physicians however physicians specialized addiction treatment certain relevant indication areas seemed sceptical compared physicians general nevertheless physicians generally experienced lack knowledge clinical effects including beneficial adverse effectsconclusionthis review indicates gps hospital physicians various specialties frequently experience patient demands medical cannabis degree show openness using although wide gap studies terms willingness provide hospital physicians gps experienced prescribing convinced effects less worried adverse effects however physicians experience lack knowledge beneficial effects adverse effects advise patients may comprise barriers towards prescribing research including larger studies cohort designs qualitative studies needed examine facilitators barriers physicians prescribing practices,0.0
growth factors roles multiple sclerosis risk front immunol 2021 oct 21 12768682 doi 103389 fimmu2021768682 ecollection 2021abstractbackground previous studies suggested essential roles growth factors risk multiple sclerosis ms remains undefined whether effects causalobjective applied mendelian randomization mr approaches disentangle causal relationship genetically predicted circulating levels growth factors risk msmethods genetic instrumental variables fibroblast growth factor fgf 23 growth differentiation factor 15 gdf15 insulin growth factor 1 igf1 insulinlike growth factor binding proteins 3 igfbp3 vascular endothelial growth factor vegf obtained uptodate genomewide association studies gwas summarylevel statistics ms obtained international multiple sclerosis genetics consortium incorporating 14 802 subjects ms 26 703 healthy controls european ancestry inversevariance weighted ivw mr used primary method multiple sensitivity analyses employed studyresults genetically predicted circulating levels fgf23 associated risk ms odds ratio ivw 063 95 confidence interval ci 049082 p 0001 per one standard deviation increase circulating fgf23 levels weighted median estimators also suggested fgf23 associated lower ms risk 067 95 ci 051087 p 0003 mregger approach provided evidence horizontal pleiotropy intercept 0003 p 095 results ivw methods provided evidence causal roles gdf1 igf1 igfbp3 vegf ms risks additional sensitivity analyses confirmed robustness null findingsconclusion results implied causal relationship fgf23 risk ms studies warranted confirm fgf23 genetically valid target mspmid34745143 pmcpmc8566812 doi103389 fimmu2021768682,0.0
clinical pathway diagnosis management patients relapsingremitting multiple sclerosis first proposal peruvian population front neurol 2021 oct 21 12667398 doi 103389 fneur2021667398 ecollection 2021abstractbackground relapsingremitting multiple sclerosis rrms subtype degenerative inflammatory demyelinating disease multifactorial origin affects central nervous system leads multifocal neurological impairment objectives develop clinical pathway cp management peruvian patients rrms methods first performed literature review using medline embase cochrane proquest science direct structured information ordered logical series five topics defined timeline 1 ms diagnosed 2 relapse treated 3 dmt initiated 4 dmt used 5 patients followed results personnel involved care patients rrms can use series flowcharts diagrams summarize topics paper electronic format conclusions propose first cp rrms peru shows essential steps diagnosing treating monitoring rrms patients based evidencebased medicine method local expert opinions cp will allow directing relevant clinical actions strengthen multidisciplinary management rrms perupmid34744956 pmcpmc8567844 doi103389 fneur2021667398,1.0
anticancer activity aqueous extracts asparagus officinalis l byproduct breast cancer cells molecules 2021 oct 21 26 21 6369 doi 103390 molecules26216369abstractcultivation asparagus asparagus officinalis l asp food medicinal use taken place since early roman empire today asp represents worldwide diffuse perennial crop lower portions spears represent food industry waste product can used extract bioactive molecules study aqueous extracts derived nonedible portion plant hard stem prepared characterized chemical content furthermore biocompatibility bioactivity asp aqueous extracts assessed vitro normal fibroblasts breast cancer cell lines results showed interference fibroblast viability remarkable cytostatic concentrationdependent activity significant g1 s cell cycle arrest specifically observed breast cancer cells without apoptosis induction asp extracts also shown significantly inhibit cell migration analyses showed asp extracts characterized specific prooxidant activity tumoral cells importantly combination menadione resulted significant enhancement oxidants production respect menadione alone breast cancer cells normal cells selectivity action tumoral cells together easiness preparation makes aqueous asp extracts attractive investigation breast cancer research particularly investigate role possible coadjuvant agents clinical drug therapiespmid34770777 doi103390 molecules26216369,0.0
intranuclear delivery hif1tmd alleviates eae via functional conversion th17 cells front immunol 2021 oct 21 12741938 doi 103389 fimmu2021741938 ecollection 2021abstractt helper 17 th17 cells involved several autoimmune diseases multiple sclerosis ms rheumatoid arthritis ra addition retinoic acid receptorrelated orphan nuclear receptor gamma t rort hypoxiainducible factor1 hif1 essential differentiation inflammatory function th17 cells investigate roles hif1 functional regulation th17 cells normal physiological condition without genetic modification nucleustransducible form transcription modulation domain tmd hif1 nthif1tmd generated conjugating hif1tmd hph1 protein transduction domain ptd nthif1tmd effectively delivered nucleus t cells without cellular cytotoxicity nthif1tmd significantly blocked differentiation nave t cells th17 cells dosedependent manner via il17a rort expression inhibition however tcell activation events induction cd69 cd25 il2 differentiation potential nave t cells th1 th2 treg cells affected nthif1tmd interestingly th17 cells differentiated nave t cells presence nthif1tmd showed substantial level suppressive activity toward activated t cells increase foxp3 il10 expression detected th17 cells mrna expression pattern compared th17 cells nthif1tmdtreated th17 cells expression genes involved differentiation functions th17 cells downregulated genes necessary immunesuppressive functions treg cells upregulated mice experimental autoimmune encephalomyelitis eae treated nthif1tmd antiil17a mab positive control therapeutic efficacy nthif1tmd vivo comparable antiil17a mab nthif1tmdmediated therapeutic effect contributed functional conversion th17 cells immunesuppressive t cells results study demonstrate nthif1tmd can new therapeutic reagent treatment various autoimmune diseases th17 cells dominant pathogenic t cellspmid34745114 pmcpmc8566938 doi103389 fimmu2021741938,0.0
adverse childhood experiences predict reaction multiple sclerosis diagnosis health psychol open 2021 oct 21 8 2 20551029211052830 doi 101177 20551029211052830 ecollection 2021 juldecabstractobjective time multiple sclerosis ms diagnosis identifying risk poorer healthrelated quality life emotional wellbeing can critical consideration treatment planning study aimed test whether adverse childhood experiences predict ms patients healthrelated quality life emotional functioning time diagnosis initial course diseasemethods recruited patients time new ms diagnosis complete selfreport surveys baseline oneyear followup questionnaires included adverse childhood experiences aces well ms knowledge questionnaire mskq 36item short form health survey sf36 selfmanagement screening semas results total n 31 participants recently diagnosed relapsing remitting ms median edss 10 age m 3384 84 years completed study measures aces significantly predicted healthrelated quality life sf36 baseline adjusted r 2 018 p 0011 followup adjusted r 2 012 p 003 baseline scores semas depression scale adjusted r 2 019 p 0008 well followup scores semas anxiety adjusted r 2 019 p 0014 semas depression adjusted r 2 014 p 0036 scales importantly increased aces scores predictive increased anxiety oneyear followup assessment compared baselineconclusions childhood adversity predicts healthrelated quality life emotional wellbeing time ms diagnosis initial course disease measured using brief screening inventory aces routine administration may useful identifying patients need increased supportive servicespmid34707881 pmcpmc8543585 doi101177 20551029211052830,0.0
update extraoral bitter taste receptors abstractbitter tastesensing type 2 receptors tas2rs t2rs belonging subgroup family gprotein coupled receptors gpcrs crucial importance perception bitterness although first instance tas2rs considered exclusively distributed apical microvilli taste bud cells numerous studies detected sensory receptor proteins several extraoral tissues pancreatic ovarian tissues well corresponding malignancies critical points extraoral tas2rs biology structure roles signaling transduction pathways extensive mutational polymorphism molecular evolution currently broadly studied tas2r cascade instance recently considered pivotal modulator number patho physiological processes including adipogenesis carcinogenesis latest advances taste receptor biology raise possibility utilizing tas2rs therapeutic target informative index predict treatment responses various disorders thus focus review provide update expression molecular basis tas2rs functions distinct extraoral tissues health disease shall also discuss therapeutic potential novel tas2rs targets appealing due ligand selectivity expression pattern pharmacological profiles,0.0
epstein barr virus exploits genetic susceptibility increase multiple sclerosis risk microorganisms 2021 oct 21 9 11 2191 doi 103390 microorganisms9112191abstractmultiple sclerosis ms autoimmune disease central nervous system cns genetic environmental risk factors identified strongest synergy among exists mhc class ii haplotype infection epstein barr virus ebv especially symptomatic primary ebv infection infectious mononucleosis elevated ebvspecific antibodies review will summarize epidemiological evidence ebv infection prerequisite ms development describe altered ebv specific immune responses ms patients speculate possible pathogenic mechanisms synergy ebv infection msassociated mhc class ii haplotype will also discuss least one mechanisms might explain recent success b celldepleting therapies ms better mechanistic understanding role ebv infection immune control ms pathogenesis required calls development innovative experimental systems test proposed mechanisms therapies targeting ebvinfected b cells already starting explored ms patientspmid34835317 doi103390 microorganisms9112191,0.0
evaluation response electric pulp testing multiple sclerosis patients without history trigeminal neuralgia casecontrol study background importance evaluating pulpal threshold electrical stimulation side effect probable neuropathy multiple sclerosis ms patients novel issue study aimed investigate electrical pulp test thresholds ms patients without history trigeminal neuralgia compared healthy individualsmethodssixtynine maxillary central incisors belonging 34 relapsingremitting ms patients 35 healthy individuals included survey ms patients matched intended variables 2250 years old 1year history ms history trigeminal neuralgia neuropathy electric pulp sensibility test performed samples electric pulp testing ept results recorded based pulp testers grade evoked response data analyzed paired ttest mannwhitney test spearman correlation p 005 resultsaccording results study mean values response ept 12 05 18 05 ms patients healthy individuals respectively pulpal response ept two groups significantly different p 00001 conclusionsms patients showed significantly reduced response electric pulp test maxillary central incisors comparison matched healthy persons,0.0
vitamin d multiple sclerosislessons animal studies front neurol 2021 oct 20 12757795 doi 103389 fneur2021757795 ecollection 2021abstractmultiple sclerosis multifactorial disease central nervous system genetic environmental causes exact disease mechanisms still unclear consequently studies possible treatment preventive measures cover large setting heterogeneous approaches vitamin d one approaches many trials relation vitamin d serum levels multiple sclerosis disease risk activity describes different effects sometimes inconsistent findings animal models substantial research disease mechanisms many drugs currently use multiple sclerosis developed tested validated via animal studies especially clinical studies show contradicting findings use standardized settings information mechanistic background necessary purpose animal models essential tool variety different experimental settings types animal models available strengths also weaknesses minireview aims overview results vitamin d studies different animal models sums important recent findingspmid34744990 pmcpmc8563695 doi103389 fneur2021757795,0.0
identifying hub genes immune infiltration osteoarthritis using comprehensive bioinformatics analysis background osteoarthritis oa common chronic degenerative joint disorder globally characterized synovitis cartilage degeneration joint space stenosis subcartilage bone hyperplasia however pathophysiologic mechanisms oa thoroughly investigatedmethodsin study conducted various bioinformatics analyses identify hub biomarkers immune infiltration oa gene expression profiles synovial tissues 29 healthy controls 36 oa samples obtained gene expression omnibus database identify differentially expressed genes degs cibersort algorithm used explore association immune infiltration arthritisresultseighteen hub degs identified critical biomarkers oa gene ontology pathway enrichment analyses found degs primarily involved pi3kakt signaling pathway rap1 signaling pathway furthermore immune infiltration analysis revealed differences immune infiltration patients oa healthy controls hub gene znf160 closely related immune cells especially mast cell activation oaconclusionoverall study presented novel method identify hub degs correlation immune infiltration may provide novel insights diagnosis treatment patients oa,0.0
body fluids rat exposed chlorpyrifos induce cytotoxicity corresponding tissuederived cells vitro background study aims establish vitro monitoring approach evaluate pesticide exposures studied vitro cytotoxicity three different body fluids rats respective corresponding tissuederived cellsmethodswistar rats orally administrated daily three different doses chlorpyrifos 130 326 815 mg kg body weight day equal doses 1 125 1 50 1 20 ld50 respectively consecutive 90 days blood samples well 24hour urine fecal samples collected processed urine serum feces samples used treat correspondent cell lines ie t24 bladder cancer cells jurkat lymphocytes ht29 colon cancer cells respectively derived correspondent tissues interact respective corresponding body fluids organism cell viability determined using mtt trypan blue stainingresultsthe results showed urine serum feces extract rats exposed chlorpyrifos displayed concentration timedependent cytotoxicity cell lines furthermore found cytotoxicity body fluids exposed animals mainly due presence 3 4 5trichloropyrindinol major toxic metabolite chlorpyrifosconclusionsthese findings indicated urine serum feces extraction especially urine combining corresponding tissuederived cell lines vitro cell models used evaluate animal exposure pesticides even low dose apparent toxicological signs animals thus vitro approach served complementary methodology existing toolbox biological monitoring longterm lowdose exposure environmental pesticide residues practice,0.0
role gliaderived extracellular vesicles neurodegenerative diseases front aging neurosci 2021 oct 20 13765395 doi 103389 fnagi2021765395 ecollection 2021abstractextracellular vesicles evs nanosized vesicles secreted almost cells recognized essential transmitter celltocell communication participating multiple biological processes neurodegenerative diseases nd alzheimers disease parkinsons disease amyotrophic lateral sclerosis share common mechanisms aggregation propagation distinct pathologic proteins among cells nervous systems neuroinflammatory reactions mediated glia pathogenic process feature indicates vital role crosstalk neurons glia pathogenesis nd recent years gliaderived evs investigated potential mediators signals neurons glia provides new direction strategy understanding nd comprehensive summary can concluded gliaderived evs beneficial detrimental effect process nd therefore review article conveys role gliaderived evs pathogenesis nd raises current limitations potential application diagnosis treatment ndpmid34744700 pmcpmc8563578 doi103389 fnagi2021765395,0.0
evidence acrolein synovial fluid dogs osteoarthritis potential inflammatory biomarker background acrolein known proinflammatory toxic aldehyde propagating cellular damage tissue inflammation humans animal models various diseases osteoarthritis oa significant inflammatory component however presence acrolein synovial fluid joints oa previously reported first aim study evaluate evidence acrolein synovial fluid dogs oa well control joints second aim determine evidence acrolein can detected synovial fluid samples frozen state long periods timemethodsin pilot clinical study synovial fluid samples prospectively collected ie new samples single joint clinically healthy new control n 5 dogs oa new oa n 16 frozen time analysis additionally frozen synovial fluid samples biobank ie old samples used evaluate ability detect evidence acrolein longterm stored samples median 489 years old control n 5 old oa n 5 samples measurements acrolein synovial fluid samples based detection major protein adduct n 3formyl3 4dehydropiperidino lysine fdplysine using western blot method synovial fluid matrix metalloproteinase 2 mmp2 measured samples using western blot method positive control oa inflammationresultsacroleinlysine adduct detected control n 10 oa n 21 groups old new samples acroleinlysine adduct mmp2 detectable lower level old compared new synovial fluid samples however differences statistically significant p 01 measured mmp2 levels significantly higher oa compared control group samples p 0033 acroleinlysine adduct p 030 conclusionsthis study confirmed evidence acrolein canine synovial fluid oa control groups freezing synovial fluid 5 years appear significantly affect ability detect acroleinlysine adduct mmp2 samples,0.0
unusual course disease genetic profile lifraumeni syndromeassociated osteosarcoma case report background osteosarcoma highly malignant tumour associated numerous complex genetic alterations like copy number alterations recent whole genome studies revealed distinct mutations several candidate oncogeneswhile clinical parameters stratify osteosarcoma patients risk groups genetic profiles yet used tailor tumour treatment however specific copy number alterations seem prognostic impact osteosarcoma treatmentsomatic tp53 gene mutation frequently occurs sporadic osteosarcoma arising germline tp53 mutation leads lifraumeni syndrome may result early life osteosarcoma effect lifraumeni syndrome genetic profile osteosarcoma consideration syndrome cancer treatment topics current researchcase presentationwe report 25yearold female pelvic osteosarcoma refusing continuation therapy interrupted neoadjuvant chemotherapy according euramos1 coss recommendations declined local adjuvant therapy surprisingly remained sustained remission osteosarcoma eventually died newly diagnosed breast cancer establishment breast cancer detected tp53 germline mutation investigated osteosarcoma material arraycghconclusiongenetic examination tumour evidenced several copy number alterations striking differences previously reported data discuss possible influences genetic profile unusual clinical course significance lifraumeni syndrome genetic profile specific loss proto oncogenes might contributed unusual case largescale genetics lifraumeni patients combined detailed clinical data will help identify specific genetic risk profiles improve treatment,0.0
site cholesterol oxidation impacts localization domain formation neuronal plasma membrane acs chem neurosci 2021 oct 11 doi 101021 acschemneuro1c00395 online ahead printabstractcholesterol integral structure mammalian cell membranes oxidation cholesterol alters behaves membrane influences membrane biophysical properties elevated levels oxidized cholesterol associated neurodegenerative diseases alzheimers disease parkinsons disease multiple sclerosis huntingtons disease previous work investigated impact oxidized cholesterol context simple model membrane systems however growing body literature shows complex membranes possessing physiological phospholipid distributions different properties binary trinary model membranes current work impact oxidized cholesterol biophysical properties complex neuronal plasma membrane investigated using coarsegrained martini molecular dynamics simulations comparison native neuronal membrane neuronal membranes containing 10 tailoxidized 10 headoxidized cholesterol shows site oxidization changes behavior oxidized cholesterol membrane furthermore speciesspecific domain formation observed oxidized cholesterol minor lipid classes although tailoxidized headoxidized cholesterols modulate biophysical properties membrane smaller changes observed complex neuronal membrane seen previous work simple binary trinary model membranes work highlights presence compensatory effects lipid diversity complex neuronal membrane overall study improves molecularlevel understanding effects oxidized cholesterol properties neuronal tissue emphasizes importance studying membranes realistic lipid compositionspmid34633798 doi101021 acschemneuro1c00395,0.0
case report covid19 multiple sclerosis patients treated ocrelizumab case series front neurol 2021 oct 20 12691616 doi 103389 fneur2021691616 ecollection 2021abstractintroduction limited data available course coronavirus disease 2019 covid19 people multiple sclerosis ms realworld data needed help ms community manage ms treatment properly particular important understand impact immunosuppressive therapies used treat ms outcome covid19 methods retrospectively collected data confirmed cases covid19 ms patients treated ocrelizumab followed two ms centers based university hospitals northern italy february 2020 june 2021 results identified 15 ms patients treated ocrelizumab confirmed covid19 mean age 5047 91 years median edss 30 range 1070 14 confirmed nasal swab 1 confirmed serological test covid19 severity mild moderate majority patients n 11 733 mean age 4973 median edss 30 four patients 267 mean age 525 years median edss 6 severe disease hospitalized one died age 50 edss 60 comorbidities none underlying respiratory comorbidities conclusion case series highlights large variability course covid19 ocrelizumabtreated ms patients challenges encountered healthcare system early phase covid19 pandemic might contributed case fatality ratio observed series higher msrelated disability associated severe covid19 coursepmid34744958 pmcpmc8563620 doi103389 fneur2021691616,0.0
effectiveness natalizumab achieving evidence disease activity neda3 data local norwegian cohort front neurol 2021 oct 20 12765837 doi 103389 fneur2021765837 ecollection 2021abstractobjective aimed determine effectiveness natalizumab ntz assessing overall evidence disease activity 3 neda3 local norwegian cohort background ntz immunomodulating drug used treatment multiple sclerosis ms typically used secondline treatment certain patients high disease activity started directly ntz methods retrospective cohort study includes patients received ntz relapsingremitting ms nordland hospital period 20082018 june 2019 status every patient assessed survival curve used show cumulative probability achieving neda3 time results cohort consisted 66 patients 49 women 17 men mean age 400 108 years patient received average 458 364 ntz infusions mean age expanded disability status scale edss first infusion 348 105 32 19 respectively prior ntz treatment 83 used disease modulating drugs 65 antijc virus jcv seronegative study period seven patients converted seropositive 2019 40 patients switched stopped treatment 19 due positive jcv serostatus 9 due disease activity 7 due adverse effects complications 1 progressive multifocal leukoencephalopathy 2 due pregnancy 3 due autologous hematopoietic cell transplantation abroad three patients experienced rebound wake discontinuation 75 patients receiving ntz 3 years n 33 50 achieved neda3 3 years compared evidence disease activity eda neda3 patients significant lower edss score first ntz treatment p 004 also slightly significantly younger debut ms diagnosis first ntz treatment patients ever started ntz 23 achieved neda3 5 years later mean edss 2019 36 25 conclusion despite high rate treatment switch mainly due risk pml almost one four started ntz achieved neda3 5 years overall disease progression low total cohort treating less advanced disease seems predict better longterm stabilitypmid34744991 pmcpmc8563783 doi103389 fneur2021765837,0.0
memantine modulates oxidative stress rat brain following experimental autoimmune encephalomyelitis int j mol sci 2021 oct 20 22 21 11330 doi 103390 ijms222111330abstractexperimental autoimmune encephalomyelitis eae animal model commonly used research pathomechanisms multiple sclerosis ms inflammatory processes glutamate excitotoxicity oxidative stress proposed determinants accompanying demyelination neuronal degeneration course ms eae aim current study characterize role nmda receptors induction oxidative stress course eae effect memantine uncompetitive nmda receptor antagonist modulation neurological deficits oxidative stress eae rats analyzed using several experimental approaches demonstrated expression antioxidative enzymes superoxide dismutases sod1 sod2 elevated eae rat brains experimental conditions observed alterations oxidative stress markers increased levels malondialdehyde mda decreased levels sulfhydryl sh groups protein nonprotein indicating protein damage decline reduced glutathione importantly pharmacological inhibition ionotropic nmda glutamate receptors antagonist memantine improved physical activity eae rats alleviated neurological deficits paralysis tail hind limbs modulated oxidative stress parameters mda sh groups sods furthermore current therapy aiming suppress nmdarinduced oxidative stress partially effective nmdars antagonist administered early asymptomatic stage eaepmid34768760 doi103390 ijms222111330,1.0
clinical application pulmonary vascular resistance patients pulmonary arterial hypertension abstractpulmonary arterial hypertension type malignant pulmonary vascular disease mainly caused increase pulmonary vascular resistance due pathological changes pulmonary arteriole eventually leads right heart failure death one diagnostic indicators hemodynamics pulmonary vascular resistance plays irreplaceable role pathophysiology diagnosis treatment pulmonary arterial hypertension provides references evaluation pulmonary arterial hypertension patients article summarizes clinical application pulmonary vascular resistance patients pulmonary arterial hypertension,0.0
performance activities daily living people multiple sclerosis abstractobjective multiple sclerosis ms may result activity participation limitations including performance activities daily living adl study aims systematically investigate adl performance using assessment motor process skills amps people ms pwms disease types within kurtzke expanded disability status scale edss range 10 80methods eight multiple sclerosis ms centres participated data collection consecutive sample pwms subjects referred assessment occupational therapy ot treating physician recruited neurology department hospital patients assessed edss amps amps observational criterion referenced adl assessment providing values patientnulls adl performance terms motor process skills criterion referenced cutoff scores established 20 motor skills 10 process skills values cutoff score indicate competent independent safe efficient effortless adl performance process skills refer act carrying series actions summarized terms efficiency like initiating without pauses continuing actions completion performing actions logical order sequencing choosing completing task planned heeding results two hundred ten pwms recruited 48 + 13 years age 145 women 65 men average disease duration 118 + 96 years average edss 48+ 18 average motor skills score 101+ 112 indicating need assistance evidence increased clumsiness physical effort average process skills score 102 + 066 risk zone questionable efficiency likely need assistance overall motor skills process skills decreased increasing edss score need assistance motor skills indicated subjects lower edss scores 10 25 higher edss group 45 57 subjects needed assistance motor skills 27 process skills competency process skills either questionable reduced within edss scores however 3338 subjects higher edss scores 6085 showed competent performance process skills overall correlation motor process scores moderate r056 p00001 significant relationships motor process skills found lower edss 125 high edss scores 885 edss disease type significant predictors explaining 527 motor skills 223 process skills performanceconclusionproblems adl performance found edss categories 10 80 disease types therefore advisable screen pwms adl deficits provide relevant rehabilitation interventions,0.0
interlimb coordination performance seated position persons multiple sclerosis reduced amplitude 6 min higher coordination variability persons walking fatigability front hum neurosci 2021 oct 20 15765254 doi 103389 fnhum2021765254 ecollection 2021abstractbackground walking fatigability prevalent ms can measured percentage distance decline 6min walking test walking characterized accurate consistent interlimb antiphase coordination pattern decline coordination minute 6min walking test observed persons ms pwms measuring coordination 6min seated coordination task minimized balance strength requirements assumed examine fundamental interlimb antiphase coordination pattern pwms research aimed answer following research question interlimb antiphase coordination pattern change seated coordination task pwms walking fatigability wf nonwalking fatigability nwf healthy controls hc methods thirtyfive pwms 13 hc participated interlimb coordination assessed seated 6min coordination task 6mct instruction perform antiphase lower leg movements fast possible outcomes phase coordination index pci movement parameters amplitude frequency results mixed models revealed significant effect time variability generating interlimb movements difference mean values wf hc significant grouptime interaction effect found movement amplitude represented significant decrease movement amplitude wf group minute 1 end task conclusion higher variability interlimb coordination decrease movement amplitude time 6mct wf group indicator decreased control fundamental antiphase coordination pattern pwms walking fatigability clinical trial registration wwwclinicaltrialsgov identifier nct04142853 registration date october 29 2019 nct03938558 registration date may 6 2019 pmid34744669 pmcpmc8564500 doi103389 fnhum2021765254,0.0
longerterm safety bcell therapy ocrelizumab multiple sclerosis neurology 2021 sep 2101212 wnl0000000000012716 doi 101212 wnl0000000000012716 online ahead printno abstractpmid34475129 doi101212 wnl0000000000012716,0.0
adaptability resilience aging adults ariaa protocol pilot feasibility study chronic low back pain background chronic low back pain clbp leading cause disability among older adults one top reasons seeking healthcare resulting significant decrements physical functioning older adults among fastest growing cohorts usa incidence burden clbp expected increase considerably rendering geriatric pain management top health priority resilience defined process allowing individuals adapt recover adverse stressful conditions highlighted crucial factor positive healthrelated functioning growing body literature supports use resiliencebased interventions chronic pain research examining effectiveness older adults clbp remains limited primary aims study assess feasibility acceptability psychologically oriented resilience intervention among aging adults clbpmethodsin article describe rationale design adaptability resilience aging adults ariaa study singlearm intervention 60 participants ages 60 years clbp will recruited participate 7week groupbased program aimed enhancing psychological resilience intervention sessions will target positive psychology concepts eg positive affect pain acceptance hopeful thinking pain selfefficacy cognitive behavioral techniques established benefits pain management primary study outcomes include intervention feasibility acceptability measured treatment engagement intervention credibility satisfaction ability meet recruitment retention metrics feasibility questionnaire home activity completion outcomes will assessed baseline immediately posttreatment 3month followup perioddiscussionthis study will establish feasibility acceptability novel intervention aimed enhancing positive psychological functioning resilience older adults clbp achievement aims will provide rich platform future intervention research targeting improvements pain disability among geriatric populations will serve foundation fully powered trial examine treatment efficacy proposed interventiontrial registrationclinicaltrialsgov identifier nct04068922 registered 28 august 2019,0.0
adjunctive cytoprotective therapies acute ischemic stroke systematic review abstractwith introduction endovascular thrombectomy evt new era treatment acute ischemic stroke ais arrived however despite much larger recanalization rate compared thrombolysis alone final outcome remains far ideal raises question previously tested neuroprotective drugs warrant reevaluation since compounds tested studies largevessel recanalization rarely achieved acute phase review provides overview compounds tested clinical ais trials gives insight drugs warrant reevaluation addon therapy ais era evt literature search performed using search terms ischemic stroke brain title abstract additional filters exclusion papers using predefined selection criteria total 89 trials eligible review reported 56 unique compounds trial compounds divided 6 categories based perceived mode action systemic haemodynamics excitotoxicity neuroinflammation bloodbrain barrier vasogenic edema oxidative nitrosative stress neurogenesis regeneration recovery main trial outcomes safety issues summarized promising compounds reevaluation highlighted looking group effect drugs intervening oxidative nitrosative stress neurogenesis regeneration recovery appear favourable safety profile show promising results regarding efficacy finally possible theories behind individual group effects discussed recommendation promising treatment strategies described,1.0
safety ocrelizumab patients relapsing primary progressive multiple sclerosis neurology 2021 sep 2101212 wnl0000000000012700 doi 101212 wnl0000000000012700 online ahead printabstractobjectiveto report safety ocrelizumab ocr 7 years patients relapsing multiple sclerosis rms primary progressive multiple sclerosis ppms enrolled clinical trials treated realworld postmarketing settingsmethodssafety analyses based integrated clinical laboratory data patients received ocr 11 clinical trials including controlled treatment openlabel extension ole periods phase 2 3 trials plus phase 3b trials veloce chords casting oboe ensemble consonance liberto selected adverse events aes additional postmarketing data used incidence rates serious infections sis malignancies contextualized using multiple epidemiologic sourcesresultsat data cutoff january 2020 5 680 patients multiple sclerosis ms received ocr 18 218 patient years py exposure clinical trials rates per 100 py 95 ci aes 248 246251 serious aes 73 7077 infusionrelated reactions 259 251266 infections 762 749774 similar within controlled treatment period phase 3 trials rates common serious aes including sis 201 181223 malignancies 046 037057 consistent ranges reported epidemiologic dataconclusioncontinuous administration ocr 7 years clinical trials well broader use 3 years realworld setting associated favorable manageable safety profile without emerging safety concerns heterogeneous ms populationclassification evidencethis analysis provides class iii evidence longterm continuous treatment ocr consistent favorable safety profile patients rms ppms study rated class iii use ole data historical controlspmid34475123 doi101212 wnl0000000000012700,0.0
inhibition lysophosphatidic acid receptor 13 deteriorates experimental autoimmune encephalomyelitis inducing oxidative stress background lysophosphatidic acid receptors lpars gproteincoupled receptors involved many physiological functions central nervous system however role lpars multiple sclerosis ms clearly defined yetmethodshere investigated roles lpars myelin oligodendrocyte glycoprotein peptidesinduced experimental autoimmune encephalomyelitis eae animal model msresultspreinhibition lpar13 antagonist ki16425 deteriorated motor disability eaelow specifically lpar13 antagonist intraperitoneal deteriorated symptoms eaelow associated increased demyelination chemokine expression cellular infiltration immune cell activation microglia macrophage spinal cords mice compared sham group lpar13 antagonist also increased infiltration cd4+ ifn+ th1 cd4+ il17+ th17 cells spinal cords eaelow mice along upregulated mrna expression ifn il17 impaired bloodbrain barrier bbb spinal cord underlying mechanism negative effects lpar13 antagonist associated overproduction reactive oxygen species ros generating nicotinamide adenine dinucleotide phosphate nadph oxidases nox 2 nox3 interestingly lpar1 2 agonist 1oleoyllpa lpa 181 intraperitoneal ameliorated symptoms eaehigh improved representative pathological features spinal cords eaehigh miceconclusionsour findings strongly suggest agents can stimulate lpars might potential therapeutic implications autoimmune demyelinating diseases ms,1.0
comparison edss timed 25foot walk 9hole peg test clinical trial outcomes relapsingremitting multiple sclerosis neurology 2021 aug 25101212 wnl0000000000012690 doi 101212 wnl0000000000012690 online ahead printabstractbackground clinical trials relapsingremitting multiple sclerosis rrms usually use expanded disability status scale edss primary disability outcome measure recently developed outcomes timed 25 foot walk t25fw nine hole peg test nhpt may useful patientrelevantobjective compare edss t25fw nhpt large rrms randomized controlled trial rct datasetmethods used dataset combirx clinicaltrialsgov identifier nct00211887 large phase 3 rct compare edss alternative outcomes t25fw nhpt investigated disability worsening versus similarly defined improvement unconfirmed versus confirmed sustained disability change presentation methods cumulative kaplanmeier survival curves versus crosssectional disability worseningresults combirx included 1 008 participants comparison confirmed versus sustained worsening events showed throughout trial substantially fewer sustained confirmed events positive predictive value confirmed sustained worsening 24 months 073 edss 073 t25fw 08 nhpt concerning finding worsening edss occurred frequently similarly defined improvement throughout three years follow improvement rates increased parallel worsening rates t25fw showed low improvement rates 10 throughout trial also found kaplanmeier survival analysis standard presentation analysis method modern rrms trials yields exaggerated estimates disability worsening using kaplanmeier method proportion patients worsening events steadily increases reaches several fold number events seen conservative analysis methods 3 month cdw 36 months kaplanmeier method yields 26 fold higher estimates edss 29 fold higher estimates t25fw 51 fold higher estimates nhpt compared conservative presentation datadiscussion analyses raise concerns using edss standard disability outcome rrms trials suggest t25fw may useful measure findings relevant design critical appraisal rctspmid34433679 doi101212 wnl0000000000012690,0.0
novel method maintaining stability freshly cultured mesenchymal stem cells clinical grade injection ready state without cryopreservation background mesenchymal stem cells mscs multipotent cells low immuonogenecity dynamic tissue repair potential explains overwhelming attention attracted regenerative therapy one notable challenge mscs therapy bench bed timeline freshly cultured mscs exceed 24 h use 24 h msc need cryopreserved can preserve cells years costly damaging process introduce method extend bench bed lifetime mscs 4 days without high cost cell damaging effects cryopreservation method based preserving mscs human plasmamethodsmscs 12 tissue samples 4 adipose 4 bone marrow 4 whartons jelly cultured expanded standard conditions cells harvested passage 2 3 washed centrifuged pelleted resuspended human plasma cell suspensions refrigerated 5 3 c stored room temperature 22 3 c sterile temperature controlled room next 7 days two tubes one group examined every 24 h assess mscs viability growth potential day 3 assessed msc cell surface markers differentiation potential adipocyte osteocyte tissues results analyzed computing overall mean applying independentsamples ttest meansresultsthe sample means cell expansion cell viability compared two refrigerator room temperature groups although gradual decrease cell growth potential cells stored 1 day stored 7 days show 80 cells remain alive 4 days storage groups cells reached 80 confluency 20 days samples stored 4 days significant differences observed two groups room temperature refrigerator stored differentiation potential adipocyte osteocyte tested day 3 positive samples analysis cell surface markers tested day 3 positive cd90 cd105 cd73 negative cd34 cd45 hladrconclusionwe present method msc culture medium using human plasma can preserve viability growth potential 4 days room refrigerator temperatures without losing stemness characteristics recommend use 5 3 c novel method will allow rapid expansion therapeutic use mscs since cells can maintained clinical grade injection ready state several days can transported across globe,1.0
efficacy cladribine tablets treatment people multiple sclerosis protocol clobas study cladribine multicenter longterm efficacy biomarker australian study jmir res protoc 2021 oct 19 10 10 e24969 doi 102196 24969abstractbackground cladribine tablets marketed mavenclad new oral therapy recently listed pharmaceutical benefits scheme australia treatment relapsing multiple sclerosis ms current dosing schedule 2 courses given year apart shown effective treatment ms 4 years 75 patients based annualized relapse rate however reinitiation therapy year 4 studiedobjective study aims evaluate safety efficacy cladribine tablets 6year period according evidence disease activity 3methods will multicenter 6year phase iv low interventional observational study incorporates clinical hematological biochemical epigenetic radiological cognitive biomarkers disease participants considered treatment cladribine part routine clinical care will consented take part study will monitored regular intervals initial course medication administration years 1 2 year 3 patients will option redosing clinically indicated switch another diseasemodifying therapy throughout duration study will assess bloodbased biomarkers including lymphocyte subsets serum neurofilament light chain dna methylation rna analysis well magnetic resonance imaging findings brain volume lesion load cognitive performanceresults study approved hunter new england local health district human research ethics committee recruitment began march 2019 completed june 2021conclusions will first longterm efficacy trial cladribine offers reinitiation therapy 3rd year based disease activity initial 2 courses expect study will indicate whether assessed biomarkers can used predict treatment efficacy need future reinitiation cladribine people mstrial registration study registered australian new zealand clinical trials registry actrn12619000257167 universal trial number u111112282165 international registered report identifier irrid derr1102196 24969pmid34665152 doi102196 24969,0.0
cerebellar degeneration primary sjgren syndrome case report background cerebellar degeneration rare severe presentation primary sjgren syndrome case reports cerebellar degeneration associated different autoimmune diseases especially systemic lupus erythematosus neurobehcets disease six patients reported worldwide affected cerebellar atrophy associated primary sjgren syndrome report describe patient primary sjgren syndrome presented ataxia due cerebellar degenerationcase presentationwe report case 37yearold chinese woman primary sjgren syndrome presented ataxia 3 months associated tremor limbs magnetic resonance imaging brain revealed bilateral cerebellar atrophy based presence cerebellar signs magnetic resonance imaging brain findings diagnosed cerebellar degeneration secondary primary sjgren syndrome treated methylprednisolone hydroxychloroquine two cycles monthly intravenous cyclophosphamide subsequently refused treatment neurological symptoms remained upon last clinic review primary cerebellar degeneration rarely associated primary sjgren syndrome pathogenesis neurological manifestations primary sjgren syndrome unclear treatment involves corticosteroids immunosuppressive agents consensus specific therapy management primary sjgren syndrome central nervous system involvementconclusionscerebellar degeneration rare presentation primary sjgren syndrome early diagnosis treatment condition needed ensure good outcome,0.0
myelin oligodendrocyte glycoprotein antibodyassociated disease varicella zoster virus infection frequency association front immunol 2021 oct 19 12769653 doi 103389 fimmu2021769653 ecollection 2021abstractto determine whether correlation myelin oligodendrocyte glycoprotein mog antibodyassociated diseases varicella zoster virus vzv infection provide case report performed study determine frequency mog antibodies mogigg neurological vzv infections patients admitted medical university innsbruck 20082020 diagnosis neurological manifestation vzv infection n59 included study patients neuroborreliosis n34 served control group mogigg detected using live cellbased assays addition performed literature review focusing mog aquaporin4 aqp4 antibodies association vzv infection case presented vzvassociated longitudinally extensive transverse myelitis mogigg titer 11280 study detect mogigg patient neither vzv group including 15 vzv encephalitis myelitis neuroborreliosis group review literature 3 cases mogigg additional 9 cases aqp4 igg associated disorders association vzv infection identified mogigg rarely detected patients vzv infections associated neurological diseasespmid34737756 pmcpmc8560958 doi103389 fimmu2021769653,1.0
multiomic evaluation metabolic alterations multiple sclerosis identifies shifts aromatic amino acid metabolism cell rep med 2021 oct 19 2 10 100424 doi 101016 jxcrm2021100424 ecollection 2021 oct 19abstractthe circulating metabolome provides unique insights multiple sclerosis ms pathophysiology existing studies relatively small characterized limited metabolites test differences metabolome people ms pwms n 637 samples healthy controls hc n 317 samples assess association metabolomic profiles disability pwms assess whether metabolic differences correlate changes cellular gene expression using publicly available scrnaseq data whether identified metabolites affect human immune cell function pwms identify striking abnormalities aromatic amino acid aaa metabolites p 277e18 also strongly associated disability p 101e4 analysis scrnaseq data demonstrates altered aaa metabolism csf bloodderived monocyte cell populations pwms treatment aaaderived metabolites vitro alters monocytic endocytosis proinflammatory cytokine production identify shifts aaa metabolism resulting reduced production immunomodulatory metabolites increased production metabotoxins pwmspmid34755135 pmcpmc8561319 doi101016 jxcrm2021100424,0.0
pirfenidone vs nintedanib patients idiopathic pulmonary fibrosis retrospective cohort study background two antifibrotic drugs pirfenidone nintedanib licensed treatment patients idiopathic pulmonary fibrosis ipf however neither evidence prospective data guideline recommendation drug preferred study aimed compare pirfenidone nintedanibtreated patients regarding allcause mortality allcause respiratoryrelated hospitalizations overall well respiratoryrelated health care costs borne statutory health insurance shi methodsa retrospective cohort study shi data performed including ipf patients treated either pirfenidone nintedanib stabilized inverse probability treatment weighting iptw based propensity scores applied adjust observed covariates weighted cox models estimated analyze mortality hospitalization weighted cost differences bootstrapped 95 confidence intervals ci applied cost analysisresultswe compared 840 patients treated pirfenidone 713 patients treated nintedanib groups similar regarding twoyear allcause mortality hr 090 95 ci 076 107 oneyear cause hr 109 95 ci 095 125 respiratoryrelated hospitalization hr 089 95 ci 072 108 significant differences observed regarding total 807 95 ci 2977 1220 respiratoryrelated 1282 95 ci 3423 534 costsconclusionour analyses suggest patientrelated outcomes mortality hospitalization costs differ two currently available antifibrotic drugs pirfenidone nintedanib hence decision treatment pirfenidone versus treatment nintedanib made casebycase taking clinical characteristics comorbidities comedications individual risk side effects patients preferences account,0.0
therapeutic role yoga neuropsychological disorders world j psychiatry 2021 oct 19 11 10 754773 doi 105498 wjpv11i10754 ecollection 2021 oct 19abstractyoga considered widelyused approach health conservation can adopted treatment modality plethora medical conditions including neurological psychological disorders hence reviewed relevant articles entailing various neurological psychological disorders gathered data yoga exerts positive impacts patients diverse range disorders including modulatory effects brain bioelectrical activities neurotransmitters synaptic plasticity role yoga practice element treatment several neuropsychological diseases evaluated based findingspmid34733640 pmcpmc8546763 doi105498 wjpv11i10754,0.0
cns involvement chronic inflammatory demyelinating polyneuropathy subtle retinal changes optical coherence tomography neurol neuroimmunol neuroinflamm 2021 oct 19 9 1 e1099 doi 101212 nxi0000000000001099 print 2022 janabstractbackground objectives chronic inflammatory demyelinating polyneuropathy cidp autoimmune disease primarily affecting peripheral nervous system however several noncontrolled studies suggested concomitant inflammatory cns demyelination similar multiple sclerosis aim study investigate involvement visual pathway patients cidpmethods prospective crosssectional study used highresolution spectraldomain optical coherence tomography compare thickness peripapillary retinal nerve fiber layer deeper macular retinal layers well total macular volume tmv 22 patients cidp 22 agematched sexmatched healthy control hc individuals retinal layers semiautomatically segmented provided software correlated clinical measures nerve conduction studiesresults patients cidp compared healthy agematched sexmatched controls found slight significant volume reductions ganglion cell inner plexiform layer complex cidp 186 vs hc 195 mm3 p 0015 retinal pigment epithelium cidp 038 vs hc 040 mm3 p 002 tmv cidp 848 vs hc 875 mm3 p 0018 ganglion cell layer volume motor nerve conduction velocity positively associated b 0002 p 002 discussion data reveal subtle retinal neurodegeneration patients cidp providing evidence visual pathway involvement detectable oct results need corroboration independent larger cohortspmid34667130 doi101212 nxi0000000000001099,1.0
evaluation agedependent immune signatures patients multiple sclerosis neurol neuroimmunol neuroinflamm 2021 oct 19 8 6 e1094 doi 101212 nxi0000000000001094 print 2021 novabstractbackground objectives ms agerelated decline disease activity decreased efficacy diseasemodifying treatment linked immunosenescence state cellular dysfunction associated chronic inflammationmethods evaluate agerelated immunologic alterations ms compared immune signatures peripheral blood pb csf flow cytometry patients relapsingremitting rr pb n 38 csf n 51 primary progressive pp ms pb n 40 csf n 36 respective controls pb n 40 csf n 85 results analysis revealed significant agerelated changes blood immune cell composition especially cd8 tcell compartment healthy donors hds patients ms however hds displayed strong agedependent decline expression immunoregulatory molecules klrg1 lag3 ctla4 memory cd8 t cells whereas agedependent reduction completely abrogated patients ms agedependent increase expression costimulatory molecule cd226 memory cd8 t cells absent patients ms cd226 expression correlated disability younger 50 years patients ms csf analysis revealed significant agedependent decline various immune cell populations ppms rrms suggesting differential effect aging intrathecal compartment ppmsdiscussion data illustrate aging ms associated dysbalance costimulatory immunoregulatory signals provided cd8 t cells favoring proinflammatory phenotype importantly pattern premature immune aging cd8 tcell compartment young patients ms potential implications disease severitypmid34667129 doi101212 nxi0000000000001094,0.0
realworld experience ocrelizumab multiple sclerosis arab population j drug assess 2021 oct 19 10 1 106113 doi 101080 2155666020211989193 ecollection 2021abstractobjective pivotal clinical trials revealed good clinical efficiency ocrelizumab good safety profile management multiple sclerosis ms however realworld data ocrelizumab daily clinical practice remain scarce aim study evaluate preliminary safety profile effectiveness ocrelizumab treatment ms arab population realworld clinical settingmethods retrospective singlecenter observational study qatar reviewed medical records analyzed clinical mri data patients relapsingremitting ms rrms active secondary progressive ms aspms october 2017 december 2020who received least one infusion ocrelizumab qocre results total 60 ms patients included 57 rrms three spms median followup period 19 months range 132 common reason switching ocrelizumab increased disease activity threequarters patients previous diseasemodifying drug dmd evidence disease activity neda status year 1 achieved 73 cohort mild infusionrelated reactions irr infections reported mainly upper respiratory tract infections followed urinary tract infection declining percentage followup applications severe side effects observedconclusion realworld experience confirms good efficacy tolerability safety ocrelizumab arab populationpmid34692185 pmcpmc8530478 doi101080 2155666020211989193,0.0
serum ykl40 levels patients multiple sclerosis abstract background multiple sclerosis ms chronic inflammatory disease affecting central nervous system ykl40 protein secreted various cells contribute inflammation infection plays role immune regulation objective study investigated serum ykl40 levels patients clinically isolated syndrome cis ms methods participants divided three groups 1 patients cis n 20 2 patients relapsingremitting ms rrms n 39 3 healthy individuals n 35 ykl40 levels serum samples obtained participants measured using enzymelinked immunoassays results median serum ykl40 level 202 ng ml range 98759 ng ml patients cis 227 ng ml range 134579 ng ml patients rrms 110 ng ml range 100173 ng ml control group p 0001 serum ykl40 levels patients rrms correlated patients expanded disability status scale scores ages p 005 relationships determined serum ykl40 levels variables p 005 serum ykl40 levels higher cis group ms group findings show serum ykl40 levels high even beginning disease serum ykl40 levels also involved progression clinically definite ms conclusions findings study suggested ykl40 may useful marker inflammatory process ms,0.0
quantitative lcms#x2f ms uncovers regulatory role autophagy immune thrombocytopenia background immune thrombocytopenia itp autoimmune haemorrhagic disease whose pathogenesis associated bone marrow megakaryocyte maturation disorder destruction haematopoietic stem cell microenvironmentmethodsin study report qualitative quantitative profiles itp proteome liquid chromatographytandem mass spectrometry lcms ms conducted elucidate protein profiles clinical bone marrow mononuclear cell bmmc samples itp patients healthy donors controls gene ontology go kyoto encyclopaedia genes genome kegg pathway analyses performed annotate differentially expressed proteins proteinprotein interaction ppi network constructed blast online database target proteins associated autophagy quantitatively identified parallel reaction monitoring prm analysisresultsour approaches showed differentially expressed autophagyrelated proteins namely hspa8 park7 ywhah itgb3 csf1r changed protein expression csf1r itp patients higher controls autophagyrelated proteins expressed lower levels itp patients controlsconclusionbioinformatics analysis indicated disruption autophagy pathway potential pathological mechanism itp results can provide new direction exploring molecular mechanism itp,0.0
safety msc therapy past 15years metaanalysis background despite increasing clinical investigations emphasizing safety mesenchymal stem cell msc therapy different populations different diseases article recently reviewed adverse events populationsaimto evaluate safety msc therapy populations receiving msc therapy explore potential heterogeneities influencing clinical application mscsmethodsthe pubmed embase web science scopus databases searched onset 1 march 2021resultsall adverse events displayed odds ratios ors 95 cis confidential intervals total 62 randomized clinical trials included enrolled 3546 participants diagnosed various diseases approximately 20 types diseases treated intravenous local implantation versus placebo treatment studies high quality neither serious publication bias serious adverse events death infection discovered across included studies pooled analysis demonstrated msc administration closely associated transient fever 365 95 ci 205649 p 001 administration site adverse events 198 95 ci 101387 p 005 constipation 245 95 ci 101597 p 005 fatigue 299 95 ci 106844 p 004 sleeplessness 590 95 ci 1043347 p 005 interestingly msc administration trended towards lowering rather boosting incidence rate arrhythmia 062 95 ci 036107 p 009 conclusionsconclusively msc administration safe different populations compared placebo modalities,0.0
roles gtpaseactivating proteins regulated cell death tumor immunity abstractgtpaseactivating protein gap negative regulator gtpase protein thought promote conversion active gtpasegtp form gtpasegdp form based ability regulate gtpase proteins domains gaps directly indirectly involved various cell requirement processes reviewed existing evidence gaps regulating regulated cell death rcd mainly apoptosis autophagy well novel rcds particular attention association diseases especially cancer also considered gaps affect tumor immunity attempted link gaps rcd tumor immunity deeper understanding gaps regulating processes lead discovery new therapeutic targets avoid pathologic cell loss mediate cancer cell death,0.0
inducing chimeric antigen receptor car regulatory t cells invivo novel concept potential feasible cure demyelinating diseases abstractchimeric antigen receptor car regulatory t cell treg therapy approved promising murine experiments comprises exvivo introduction cars tregnulls recipient infusing back thereafter process requires enormous amounts equipment expertise therefore considered feasible people demyelinating diseases even proves effective safe future presented novel concept introduces feasibility car treg therapy shifting exvivo processes invivo interdisciplinary discussions concepts encouraged among experts different fields,1.0
longterm dynamics multiple sclerosis iron rim lesions abstractbackgroundseveral studies pointed seemingly chronic multiple sclerosis ms lesions may also inflammatory states pathological studies 40 chronic ms lesions characterized chronic active smoldering lesions characterized rim ironladen proinflammatory macrophages microglial cells lesion edge lowgrade continuous myelin breakdown vivo lesions can visualized iron rim lesions irls susceptibilityweighted imaging swi aim study investigate longterm dynamics irls vivo detailed evolution dynamic lesion volume changes occurring timemethodswe retrospectively identified patients ms followed least 36 months 72 months underwent least annual mri 3 tsystem using voxelguided morphometry vgm investigated regional volume changes within lesions correlated findings swi presence characteristic hypointense lesion rim estimate tissue damage apparent diffusion coefficient adc values every lesion baseline followup mris determinedresultsfortythree patients included study overall identified 302 supratentorial nonconfluent ms lesions 52 persistent irls nine transient irls 228 nonirls 13 acute contrastenhancing lesions followup persistent irls significantly enlarged whereas nonirls showed tendency shrink baseline mri adc values significantly higher persistent irls 123103mm s2 compared nonirls 101103mm s2 p 0001 compared transient irls 106103mm s2 p015 contrastenhancing lesions 115103mm s2 p10 followup adc values significantly increased often persistent irls compared lesion types p 00001 conclusionsour longterm data demonstrate persistent irls enlarge disease duration whereas nonirls show tendency shrink furthermore irls associated sustained tissue damage supporting notion irls represent new imaging biomarker ms,1.0
systematic review effects cannabis cognition people multiple sclerosis abstractbackground multiple sclerosis ms chronic demyelinating disease leads sensory motor autonomic cognitive symptoms cannabis common way persons ms pwms seek symptomatic therapy given capacity cannabis ms cause cognitive impairment important determine whether negative impact two cooccur objective systematic review evaluate effects cannabis medicinal cannabinoid products cognition pwms order provide guidance clinicians enable make evidencebased recommendations regarding cannabis cannabinoid productsmethods systematic review carried searching common keyword combinations cannabis ms across five databases producing 840 unique articles 18 included qualitative synthesisresults aggregate data existing studies date highlight potential impairments chronic wholeplant cannabis use commonly affected cognitive domains multiple sclerosis including attention working memory lesser extent visual memory verbal memory executive function results also suggest shortterm medicinal cannabinoid preparations significantly impair cognition may even ameliorate cognitive symptoms context obtrusive ms disease findings limited disparities detail cannabis use data reported across wholeplant cannabis publicationsconclusion existing literature cooccurrence cannabis use ms lacks high quality evidence recommend cannabis cannabinoid therapies pwms based cognitive effects existing data suggest cognition may differentially impacted pwms depending type product duration use indication future studies wholeplant cannabis require comprehensive cannabis use data reporting including frequency dosing duration type cannabis product future studies medicinal cannabinoid products longterm assess effects chronicity,1.0
somatosensory evoked potentials clinical practice review abstract authors present review current use somatosensory evoked potentials sseps neurological practice noninvasive neurophysiological technique purpose reviewed articles published english portuguese pubmed lilacs databases review address role sseps neurological diseases affect central nervous system peripheral nervous system especially demyelinating diseases monitoring coma trauma functioning sensory pathways surgical procedures latter along new areas research become one important applications sseps,1.0
current utilization research status traditional east asian herbal medicine treatment multiple sclerosis scoping review front neurol 2021 oct 18 12710769 doi 103389 fneur2021710769 ecollection 2021abstractbackground multiple sclerosis ms chronic immunemediated inflammatory disease central nervous system gradually increasing prevalence etiology ms remains unknown however assumed caused deterioration autoimmune regulation although immunomodulatory agents standard treatment option patients ms insufficient evidence clinical efficacy symptomatic treatment many ms patients resort complementary alternative medicine reason conducted scoping review investigate current status clinical evidence related traditional east asian herbal medicine treatment ms inform future research treatment strategies method scoping review emerging methodology knowledge synthesis adopts arksey omalley framework research question studied herbal medicine treatments administered patients ms articles published 2019 identified six databases pubmed embase cochrane koreamed ndsl oasis march 2020 data included studies charted descriptively analyzed relation studys research questions results 1 445 articles identified 14 studies included review single serial case reports constituted majority 4286 5714 studies conducted china total 20 prescriptions containing 95 herbs used intervention observational studies herbal medicines effective improving clinical symptoms ms reducing recurrence frequency main cause ms presumed oxidative stress enhances inflammation consequently causes neuronal death conclusion herbal medicines determined improve symptoms ms reduce frequency recurrences study suggests herbal medicines promising worth pursuing studies state current evidence poor thus highquality studies included larger randomized trial requiredpmid34733228 pmcpmc8559786 doi103389 fneur2021710769,0.0
memory rehabilitation people multiple sclerosis cochrane database syst rev 2021 oct 18 10cd008754 doi 101002 14651858cd008754pub4abstractbackground problems cognition particularly memory common people multiple sclerosis ms can affect ability complete daily activities can negatively affect quality life last years considerable growth number randomised controlled trials rcts memory rehabilitation ms guide clinicians researchers review provides overview effectiveness memory rehabilitation people msobjectives determine whether people ms received memory rehabilitation compared received treatment active control showed better immediate intermediate longerterm outcomes 1 memory functions 2 cognitive abilities 3 functional abilities terms activities daily living mood quality lifesearch methods searched central includes clinicaltrialsgov world health organization whoqol international clinical trials registry portal embase pubmed medline following electronic databases 6 september 2020 cinahl lilacs nihr clinical research network portfolio database allied complementary medicine database psycinfo cab abstractsselection criteria selected rcts quasircts memory rehabilitation cognitive rehabilitation people ms memory rehabilitation treatment group compared control group selection conducted independently first confirmed group discussion excluded studies included participants whose memory deficits result conditions ms unless identify subgroup participants ms separate resultsdata collection analysis eight review authors involved update terms study selection quality assessment data extraction manuscript review contacted investigators primary studies information required conducted data analysis synthesis accordance cochrane methods performed best evidence synthesis based methodological quality primary studies included outcomes considered separately immediate within first month completion intervention intermediate one six months longerterm six months time pointsmain results added 29 studies update bringing total 44 studies involving 2714 participants interventions involved various memory retraining techniques computerised programmes training using internal external memory aids control groups varied format assessmentonly groups discussion games nonspecific cognitive retraining attention visuospatial training risk bias amongst included studies generally low found eight studies high risk bias related certain aspects methodology abstract reporting outcomes intermediate timepoint ie one six months found slight difference groups subjective memory smd 023 95 ci 011 035 11 studies 1045 participants highquality evidence quality life smd 030 95 ci 002 058 6 studies 683 participants highquality evidence favoring memory rehabilitation group small difference groups verbal memory smd 025 95 ci 011 040 6 studies 753 participants lowquality evidence information processing smd 027 95 ci 000 054 8 studies 933 participants lowquality evidence favoring memory rehabilitation group found little difference groups visual memory smd 020 95 ci 011 050 6 studies 751 participants moderatequality evidence working memory smd 016 95 ci 009 040 8 studies 821 participants moderatequality evidence activities daily living smd 006 95 ci 036 024 4 studies 400 participants highquality evidence authors conclusions evidence support effectiveness memory rehabilitation outcomes assessed review intermediate followup evidence suggests memory rehabilitation results betweengroup differences favoring memory rehabilitation group intermediate time point subjective memory verbal memory information processing quality life outcomes suggesting memory rehabilitation beneficial meaningful people ms differential effects memory rehabilitation based quality trials studies high risk bias inflating positive outcomes robust largescale multicentre rcts better quality reporting using ecologically valid outcome assessments including health economic outcomes assessed longerterm time points still needed certain effectiveness memory rehabilitation people mspmid34661282 doi101002 14651858cd008754pub4,0.0
genetic spectrum clinical features cohort chinese patients autosomal recessive cerebellar ataxias background although many causative genes uncovered recent years genetic diagnosis still missing approximately 50 autosomal recessive cerebellar ataxia arca patients studies performed determine genetic spectrum clinical profile arca patients chinese populationmethodsfiftyfour chinese index patients unexplained autosomal recessive sporadic ataxia investigated wholeexome sequencing wes copy number variation cnv calling exomedepth likely causal cnv predictions validated cnvseqresultsthirtyeight mutations including 29 novel ones identified 25 54 patients providing 463 positive molecular diagnostic rate ten different genes involved four common genes sacs syne1 adck3 setx accounted 760 19 25 positive cases de novo microdeletion sacs reported first time china uniparental disomy adck3 reported first time worldwide clinical features patients carrying sacs syne1 adck3 mutations summarizedconclusionsour results expand genetic spectrum clinical profiles arca patients demonstrate high efficiency reliability wes combined cnv analysis diagnosis suspected arca emphasize importance complete bioinformatics analysis wes data accurate diagnosis,0.0
relationships changes daily occupations healthrelated quality life persons multiple sclerosis covid19 pandemic abstractbackground covid19 pandemic provided unique opportunity explore impact mandated lockdown social distancing policies engagement daily occupations individuals multiple sclerosis ms able bodied ie healthy adults study also examined whether changes daily occupations associated healthrelated quality life hrqol methods spring early fall 2020 69 persons ms 95 healthy adults completed online survey included measurements 26 activities daily life activity participants reported whether continued perform activity without adjustments whether stopped started perform activity pandemic social support hrqol demographics including financial distress also obtainedresults participants ms healthy adults reduced number activities performed pandemic healthy adults continued activities without adjustments compared participants ms groups better hrqol associated number activities participants continued without adjustments worse hrqol number activities stopped doingconclusions fewer persons ms engaged everyday occupations healthy adults following covid19 pandemic ability maintain occupational engagement participate social daily activities important maintaining high hrqol groups thus results call attention treatment selfmanagement ms symptomatology,0.0
impaired antioxidant keap1nrf2 system amyotrophic lateral sclerosis nrf2 activation potential therapeutic strategy background oxidative stress os imbalance oxidant antioxidant species together numerous pathological mechanisms leads degeneration death motor neurons mns amyotrophic lateral sclerosis als main bodytwo main players molecular cellular response os nrf2 transcription nuclear factor erythroid 2related factor 2 principal negative regulator keap1 kelchlike ech erythroid cellderived protein cnc homology associated protein 1 first provide overview structural organization regulation critical role keap1nrf2 system counteracting os focus alteration als examine several compounds capable promoting nrf2 activity thereby inducing cytoprotective effects currently different stages clinical development many pathologies including neurodegenerative diseasesconclusionsalthough challenges associated compounds remain important advances made development safer effective drugs actually represent breakthrough fatal degenerative diseases als,0.0
potential role covid19 pathogenesis multiple sclerosisa preliminary report viruses 2021 oct 17 13 10 2091 doi 103390 v13102091abstractcoronavirus 2019 covid19 infectious respiratory disease caused severe acute respiratory syndrome coronavirus 2 sarscov2 mainly affects lungs covid19 symptoms include presence fevers dry coughs fatigue sore throat headaches diarrhea loss taste smell however understood sarscov2 neurotoxic neuroinvasive enter central nervous system cns via hematogenous route via peripheral nerve route causes encephalitis encephalopathy acute disseminated encephalomyelitis adem covid19 patients review discusses possibility sarscov2mediated multiple sclerosis ms development future comparable surge parkinsons disease cases following spanish flu 1918 moreover sarscov2 infection associated cytokine storm review highlights impact modulated cytokines glial cell interactions within cns role potentially prompting ms development secondary disease sarscov2 sarscov2 neurotropic interfere various functions neurons leading ms development influence neuroinflammation microglia phagocytotic capabilities well hypoxiamediated mitochondrial dysfunction neurodegeneration mechanisms may ultimately trigger ms developmentpmid34696521 doi103390 v13102091,0.0
phenotypic intrafamilial variability including h syndrome rosaidorfman disease associated c1088ggt mutation slc29a3 gene background mutations slc29a3 gene encodes nucleoside transporter hent3 implicated syndromic forms histiocytosis including h syndrome pigmented hypertrichosis insulindependent diabetes faisalabad histiocytosis familial rosaidorfman disease rdd herein report five new patients single family present phenotypes associate features h syndrome familial rosaidorfman diseasemethodswe investigated clinical biochemical histopathological molecular findings five tunisian family members diagnosed familial rdd h syndrome solute carrier family 29 nucleoside transporters member 3 slc29a3 gene screened molecular diagnosis using direct sanger sequencingresultsgenetic analysis affected individuals revealed previously reported missense mutation c1088 g parg363gln exon 6 slc29a3 gene four affected members presented clinical features consistent classical h syndrome phenotype cousins features keeping familial rosaidorfman disease diagnosis previously undescribed cutaneous rdd presenting erythematous nodular plaques face report underlines clinical variability slc29a3 disorders even identical mutation familyconclusionwe report rare event 5 tunisian family members found homozygous slc29a3 gene mutations showing different phenotype severity study reveals despite single mutation clinical expression slc29a3 disorders may significantly heterogeneous suggesting poor genotypephenotype correlation disease,0.0
tumor necrosis factor alpha blockade multiple sclerosis exploring new avenues cureus 2021 oct 17 13 10 e18847 doi 107759 cureus18847 ecollection 2021 octabstractmultiple sclerosis ms common disabling disease central nervous system cns progressive neurodegenerative pattern characterized demyelination white matter cns apoptosis oligodendrocytes tumor necrosis factor tnf alpha major cytokine pathogenesis ms however failure tnf alpha inhibitors preclinical clinical trials disapproved use ms patients nevertheless failures misses sometimes open avenues new hits later years discovered tnf signaling mediated via two different receptors tnfr1 tnfr2 paradoxical effects tnfr1 mediates demyelination apoptosis tnfr2 promotes remyelination neuroprotection explained cause failure nonselective tnf alphablockers ms also enlightened researchers repurposing previously formulated nonselective tnf alphablockers using receptorselective approach lead discovering novel biologic agents broader spectrum indications better safety profiles review focuses novel premier tnfr1 blocker atrosab tested animal models ms experimental autoimmune encephalomyelitis eae demonstrated reduction symptom severity early promise shown atrosab preclinical studies given us hope find another revolutionary drug ms future clinical trials will finally decide whether drug can used better therapeutic agent ms still going currently approved evidence regarding efficacy agents treating mspmid34804701 pmcpmc8597935 doi107759 cureus18847,1.0
association risk brucellosis genetic variations microrna146a background single nucleotide polymorphisms snps common types dna changes human genome leading phenotypic differences humans micrornas mirnas usually affected various bacterial infections involved controlling immune responses microrna146a mir146a plays essential role development infectious inflammatory diseases aim present study investigate association risk brucellosis genetic variations mir146amethodsthis casecontrol study conducted 108 brucellosis patients 108 healthy controls genotyped two snps rs2910164 rs57095329 mir146a using tetraprimer amplification refractory mutation systempolymerase chain reaction tarmspcr restriction fragment length polymorphismpolymerase chain reaction rflppcr methodsresultsthe rs2910164 snp significantly associated brucellosis codominant 427 95 ci 235779 p 0001 dominant 352 95 ci 197630 p 0001 models codominant p 0047 recessive p 0018 models significant position rs57095329 two groups patient healthy c haplotype rs2910164 rs57095329 associated brucellosis assessed population 95 ci 198 122320 p 00059 conclusionsconsequently study demonstrated significant differences genotype haplotype frequencies mir146a variants brucellosis patients controls studies larger sample sizes required verify observed associations,0.0
comparing traditional modeling approaches versus predictive analytics methods predicting multiple sclerosis relapse abstractobjectivethis study compared traditional statistical methods different predictive analytics methods endpoint multiple sclerosis ms relapsestudy settingthis secondary data analysis four different ms centers based third year data july 2019june 2020study designthe parent study twopart 3year clinical quality improvement prospective study started june 2017 concluded june 2020 utilizes prospective steppedwedge randomized design binary logistic regression compared machine learning models specifically ridge least absolute shrinkage selection operator lasso random forestdata collectionthis study used electronic health record data extracted individual level rolled system population level inclusion criteria included participants aged 18 years older ms presenting four centers entered study quarter exclusion criteria included cases missing incorrectly input data refused participate studyprincipal findingswhen comparing relapse indices across models random forest significantly outperformed logistic regression machine learning algorithms perfa 271 perfm 275 however perff logistic regression random forest performed relatively ridge lasso outperformed logistic regression perfm1 09 perfm2 94 perff2258 respectively conclusionmultiple sclerosis complex costly chronic 3c condition currently cure condition like ms unpredictable course use predictive analytics help health systems learn better faster improve effectively predict rather react emerging health needs people ms comparing predictability relapse across various models predictive analytics framework can potentially change manage ms care,0.0
effects voice rehabilitation people ms doubleblinded longterm randomized controlled trial abstractbackgroundhypophonia prevailing problem people multiple sclerosis pwms however evidence supporting effectiveness voice rehabilitation lackingobjectivethe aim study identify effective method reduce hypophoniamethodsin randomized controlled trial 44 pwms randomized intensive higheffort voice treatment groups lsvtloud conventional treatment group subjects received 16 treatments 4 sessions week lasting 45minutes primary outcome voice intensity db monologue vocalization sentences voice handicap index vhi measured voice selfperception outcomes assessed blinded observer baseline posttreatment 15month followup fu resultslinear models revealed significant postintervention betweengroup mean difference favor lsvtloud monologue +63db 95 ci 25 101 vocalization +74db 95 ci 23 125 sentences +95db 95 ci 47 143 however 437 pwms lsvtloud 10 conventional treatment group obtained full recovery voice intensity 60db posttreatment fishers test133 p001 however improvements maintained fu betweengroup differences vhi 108 95 ci 212 04 113 95 ci 243 17 favor lsvtloud post fuconclusionlsvtloud can valid treatment increase voice intensity pwms however results suggest need fu interventions targeting maintenance,0.0
white matter injury germinal matrix hemorrhage induces elevated osteopontin expression human preterm brains abstractosteopontin opn matricellular protein mediates various physiological functions implicated neuroinflammation myelination perinatal brain injury however expression association brain injury preterm infants unexplored examined expression opn postmortem brains preterm infants explored expression affected brain injury analyzed brain sections cases white matter injury wmi cases germinal matrix hemorrhage gmh compared control cases brain injury wmi cases displayed moderate severe tissue injury periventricular deep white matter accompanied increase microglia amoeboid morphology apart visible hemorrhage germinal matrix gmh cases displayed diffuse white matter injury periventricular deep white matter noninjured preterm brains opn expressed low levels microglia astrocytes oligodendrocytes opn expression significantly increased regions white matter injury wmi cases gmh cases main cellular source opn white matter injury areas amoeboid microglia although significant increase also observed astrocytes wmi cases opn expressed germinal matrix case regardless whether hemorrhage conclusion preterm brain injury induces elevated opn expression microglia astrocytes increase found sites closely related injury white matter regions hemorrhage site germinal matrix thus appears opn takes part inflammatory process white matter injury preterm infants findings facilitate understanding opns role physiological pathological conditions human brain may lead greater elucidation disease mechanisms potentially better treatment strategies,1.0
safety immune effects blocking cd40 ligand multiple sclerosis neurol neuroimmunol neuroinflamm 2021 oct 15 8 6 e1096 doi 101212 nxi0000000000001096 print 2021 novabstractbackground objectives costimulation cd40 ligand cd40l cd154 important functional differentiation t cells preclinical studies recognized importance costimulatory interaction pathogenesis experimental models multiple sclerosis ms determine safety pharmacokinetics immune effect humanized monoclonal antibody mab cd40 ligand toralizumab idec131 patients relapsingremitting ms rrms methods singleinstitution openlabel doseescalation study phase enrolled 12 patients rrms receive 4 doses 1 5 10 15 mg kg humanized cd40l toralizumab iv infusion every week patients followed 18 weeks annually finally 5 years addition safety pharmacokinetics secondary exploratory measurements immune effects clinical mri laboratory neuropsychological evaluationsresults fifteen adverse events mild moderate severity considered possible unknown relationship treatment serious adverse events including thromboembolic events occurred 18week defined study period annual longterm followup 5 years revealed delayed toxicity pharmacokinetics nonlinear 5 10 mg kg dose groups serum halflife toralizumab consistent dose groups mean 153 days sd 19 flow cytometry revealed depletion lymphocyte subsets increase cd25+ cd3+ cd25+ cd4+ ratio shift toward antiinflammatory cytokine response seen treatmentdiscussion study suggests blocking cd40l safe well tolerated patients rrms increasing cd25 + t cells antiinflammatory cytokine profile findings support studies assess efficacy blocking cd40l potential treatment rrmsclassification evidence study provides class iv evidence safety pharmacokinetics immune effects mab cd40l patients rrmspmid34654708 doi101212 nxi0000000000001096,0.0
global prevalence depression suicide ideation attempts military forces systematic review metaanalysis cross sectional studies background given wide range depressive disorders suicidal ideation suicide attempts various military studies around world determining exact prevalence disorders line health planning well care treatment service designing military forces can useful aim present metaanalysis determine pooled prevalence depressive disorders suicide thoughts attempts militarymethodsthe present systematic review metaanalysis study performed based prisma criteria 5 steps search strategy screening selection articles data extraction evaluation article quality metaanalysis international databases pubmed medline scopus web science embase elsevier psycinfo ovid cochrane central ovid searched using related keywords extracted mesh emtree screening final selection articles data extracted qualitative evaluation performed using nos checklistresultsthe results metaanalysis showed prevalence depression active military forces veterans 23 95 ci 2026 20 95 ci 1822 respectively addition prevalence suicidal ideation attempts military 11 95 ci 1013 11 95 ci 913 respectively prevalence suicide ideation attempts drugusing military 18 95 ci 733 30 95 ci 2336 respectively prevalence suicidal ideation attempts military consuming alcohol 9 95 ci 413 8 95 ci 710 respectively militaries aids hiv prevalence suicide attempts 5 95 ci 48 conclusiontherefore necessary develop design training intervention programs order increase awareness military especially veterans prevent occurrence suicide depression,0.0
neurosarcoidosis mimicry ms clues cases cns tissue diagnosis j neurol sci 2021 aug 23 429117621 doi 101016 jjns2021117621 online ahead printabstractthe clinical picture neurosarcoidosis ns shares many aspects multiple sclerosis ms examine whether clinical measures can reliably distinguish ns mimicking ms ns coexisting ms informative role biopsy autopsy evidence may play understanding two disorders uniquely challenging explore rare patients presenting differential ms acute disseminated encephalomyelitis adem versus ns including ms adem associated illness patients systemic sarcoidosis ns patients red flags diagnosis ms strong enough rule common disorder biopsy autopsy findings indicate tendency ns granulomatous changes cns involve deep white matter perivascular spaces expected occur ms hence correlate tendency ns involving white matter produce classic mri findings ms spectrum ns includes cases limited single anatomical site including sites classically involved demyelinating cis optic nerve brainstem transverse myelitis asymptomatic nonspecific periventricular mri changes described many studies mslike biopsied autopsied cases yet proven associated classic pathological changes ms patients nspmid34455208 doi101016 jjns2021117621,1.0
project y search clues explaining phenotype variability ms abstractbackgroundto study phenotypic variability ms patients welldefined unbiased cohort studies necessary common probably important confounding factor studying disease phenotype ms ageobjectiveto describe study design subject characteristics unique birth cohort project y overall aim project y identify determinants associated phenotypic variability ms eliminating possibility confounding agemethodsproject y populationbased crosssectional study people ms born netherlands 1966 patients healthy controls subjected comprehensive examinations functional static imaging physical cognitive measurements lifestyle factors early later life addition body fluids collected stored future biomarker researchresults452 eligible ms patients identified december 2017 january 2021 367 ms patients 125 healthy controls participated total number identified cases results current prevalence least 189 100000 people born year 1966 netherlandsconclusionproject y unique cohort designed identify factors associated phenotypic variability ms patients without confounding effects age first description project y cohort indicates prevalence ms netherlands might higher previously presumed various studies using project y data ongoing results will published upcoming years,0.0
b cell depletion changes immune cell profile multiple sclerosis patients oneyear report j neuroimmunol 2021 jul 30 359577676 doi 101016 jjneuroim2021577676 online ahead printabstractb cell depletion therapy shown beneficial multiple sclerosis ms however mechanism b cell depletion mediates beneficial effects ms still unclear better understand b cell depletion may benefit patients disease previously thought primarily mediated cd4 t cells immune profiles monitored 48 patients phase ii trial ublituximab glycoengineered cd20 monoclonal antibody 18 time points year previously described significant shift percentages t cells nk cells myeloid cells following initial dose ublituximab shift normalized within week populations remained stable duration study however t cell subsets changed increase percentage nave cd4 cd8 t cells decline memory t cells importantly percentage th1 cd4+gmcsf+ t cells decreased percentage tregs continued increase year ublituximab depleted cd20+ b cells also cd20+ t cells favorable changes t cell subsets may contribute beneficial effects b cell depletion therapypmid34364105 doi101016 jjneuroim2021577676,0.0
noncoding rnas extensive interactive regulators bloodbrain barrier permeability rna biol 2021 jul 9 doi 101080 1547628620211950465 online ahead printabstractthe bloodbrain barrier bbb controls permeability nervous system tightly connected structural functional separation central nervous system cns circulating blood cns diseases alzheimers disease multiple sclerosis traumatic brain injury stroke meningitis brain cancers often develop increased bbb permeability leads irreversible cns injury noncoding rnas ncrnas functional rna molecules generally lack coding abilities can actively regulate mrna expression function different mechanisms various types ncrnas including micrornas mirnas long ncrnas lncrnas circular rnas circrnas highly expressed brain microvascular endothelial cells potential mediators bbb permeability summarized recent research progress mirna lncrna circrna roles regulating bbb permeability different cns diseases understanding ncrnas affect bbb permeability shall provide important therapeutic insights prevention control bbb dysfunctionpmid34241576 doi101080 1547628620211950465,0.0
separation magnetic susceptibility source separation toward iron myelin mapping brain neuroimage 2021 jul 6118371 doi 101016 jneuroimage2021118371 online ahead printabstractobtaining histological fingerprint invivo brain longstanding target magnetic resonance imaging mri particular noninvasive imaging iron myelin involved normal brain functions histopathological hallmarks neurodegenerative diseases practical utilities neuroscience medicine propose biophysical model describes individual contribution paramagnetic eg iron diamagnetic eg myelin susceptibility sources frequency shift transverse relaxation mri signals using model develop method separation generates voxelwise distributions two sources method validated using computer simulation phantom experiments applied exvivo invivo brains results delineate wellknown histological features iron myelin specimen healthy volunteers multiple sclerosis patients new technology may serve practical tool exploring microstructural information brainpmid34242783 doi101016 jneuroimage2021118371,1.0
regulation autoreactive cd4 t cells foxo1 signaling cns autoimmunity j neuroimmunol 2021 jul 31 359577675 doi 101016 jjneuroim2021577675 online ahead printabstractmyelinspecific cd4 t effector cells teffs th1 th17 cells encephalitogenic experimental autoimmune encephalomyelitis eae welldefined murine model multiple sclerosis ms implicated ms pathogenesis forkhead box o 1 foxo1 conserved effector molecule pi3k akt signaling critical differentiation cd4 t cells t helper subsets however unclear whether foxo1 may target redirecting cd4 t cell differentiation benefit cns autoimmunity using selective foxo1 inhibitor as1842856 show inhibition foxo1 suppressed differentiation expansion th1 cells transdifferentiation th17 cells encephalitogenic th1like cells suppressed foxo1 inhibition upon reactivation myelinspecific cd4 t cells eae mice transcriptional balance skewed th1 transcription factor tbet toward treg transcription factor foxp3 myelinspecific cd4 t cells treated foxo1 inhibitor less encephalitogenic adoptive transfer eae studies inhibition foxo1 t cells ms patients significantly suppressed expansion th1 cells furthermore foxo1 inhibition as1842856 promoted development functional itreg cells immune checkpoint programmed cell death protein1 pd1 induced foxp3 expression cd4 t cells impaired foxo1 inhibition data illustrate important role foxo1 signaling cns autoimmunity via regulating autoreactive teff treg balancepmid34403862 doi101016 jjneuroim2021577675,1.0
survey quality life italian patients fabry disease diseases 2021 oct 15 9 4 72 doi 103390 diseases9040072abstractfabry disease fd genetic disease included group lysosomal storage disorders caused xlinked deficiency enzyme alphagalactosidase aim study evaluate different aspects related quality life qol multicentre cohort italian patients fd observational survey conducted measure healthrelated quality life hrqol fd patients using capi computerassisted personal interview method 106 patients mostly women responded questionnaire geographically 537 patients lived northern italy 189 central italy 274 southern italy islands data collected fivedimensional euroqol questionnaire referring functional aspects mobility personal care routine activities perception physical mental wellbeing pain discomfort anxiety depression descriptive analysis responses performed fd patients compared terms qol subjects suffering chronic diseases crohns disease chronic hepatitis cirrhosis multiple sclerosis difficulty normal daily activities reported 472 fd patients one third subjects also mobility difficulties feelings loneliness isolation reported 333 6069 years old anxiety equally reported oldest youngest patients 667 depression relational problems fear peoples judgement increased along age reaching 667 over70years group male patients largely troubled risk physical disability particularly aged 60 years furthermore fd patients poorer qol people suffering chronic inflammatory disorders study upholds fd patients poor qol already known negatively impacting psychic wellbeing social activities survey also found worse qol fd patients compared severe chronic disorderspmid34698147 doi103390 diseases9040072,0.0
autoimmune gfap astrocytopathy presenting remarkable cns hyperexcitability oculogyric crises j neuroimmunol 2021 aug 14 359577695 doi 101016 jjneuroim2021577695 online ahead printabstractthe autoimmune gfap astrocytopathy associated meningoencephalomyelitis usually responds glucocorticoids report 20yearold man developed acute severe meningoencephalomyelitis remarkable cns hyperexcitability oculogyric crises csf analysis showed hypoglycorrhachia pleocytosis elevated ada csfimmunofluorescence characteristic autoimmune gfap astrocytopathy mri showed lesions thalamus corpuscallosum dorsal pons dentate nucleus associated myelitis immunotherapy led full recovery although mri activity observed followup cns hyperexcitability typically seen immunemediated syndromes represents novel presenting form included part clinical spectrum entitypmid34416409 doi101016 jjneuroim2021577695,0.0
antihbs titers decreased treatment oral cladribine patients multiple sclerosis vaccinated hepatitis b virus abstractbackgroundoral cladribine novel treatment multiple sclerosis ms purine nucleoside antimetabolite analogue incorporated dna resulting singlestrand breaks dna apoptosis replicating lymphocytes specifically cladribine induces limited depletion cd4 cd8 t subsets marked depletion memory b cell subsets therefore natural acquired humoral responses pathogens may potentially reduced aim study assess longitudinal variation antihbs titers patients ms treated cladribinemethodspatients ms treated 1 cycle cladribine 3 5 mg kg previously vaccinated hepatitis b virus hbv enrolled antihbs titers compared pre 12 months cladribine treatment total lymphocyte count also analysedresultsamong 13 rms patients 10 f 3 m mean age 33 8 sd 5 9 enrolled antihbs titers 10 mg dl baseline antihbs titer dropped reference value 12 months cladribine 1 case prepost cladribine mean antihbs values significantly different considering whole cohort wilcoxonmannwhitney test p0 762 four patients grade 1 1 patient grade 2 lymphocytopenia 12 monthsconclusions cladribine seem reduce humoral immune responses subjects previously vaccinated hbv even case lymphocytopenia results confirmed larger populations appear reassuring also vaccinations ie covid19 low impact cladribine plasma cells may explain findings,0.0
covid19 cladribinetreated patient multiple sclerosis j neuroimmunol 2021 aug 8 359577690 doi 101016 jjneuroim2021577690 online ahead printabstractcase report describing patient infected covid19 initiation cladribine favorable disease course positive seroconversionpmid34390951 doi101016 jjneuroim2021577690,0.0
galectins ligand glycoconjugates central nervous system physiological pathological conditions front neuroanat 2021 oct 15 15767330 doi 103389 fnana2021767330 ecollection 2021abstractgalectins galactosidebinding lectins consisting 15 members mammals galectin1 3 4 8 9 predominantly expressed central nervous system cns regulate various physiological pathological events review summarizes current knowledge cellular expression role galectins cns discusses functions neurite outgrowth myelination neural stem progenitor cell niches well ischemic hypoxic traumatic injuries neurodegenerative diseases multiple sclerosis galectins expressed neurons glial cells galectin1 mainly expressed motoneurons whereas galectin3positive neurons broadly distributed throughout brain especially hypothalamus indicating function regulation homeostasis stress response endocrine autonomic system astrocytes predominantly contain galectin1 galectin3 and9 upregulated along activation activated resting microglia contain galectin3 supporting phagocytic activity galectin1 3 4 characteristically expressed oligodendrocyte differentiation galectin3 microglia promotes oligodendrocyte differentiation myelination galectin1 axonal galectin4 suppress differentiation myelination galectin1 3positive cells involved neural stem cell niche formation subventricular zone hippocampal dentate gyrus migration newly generated neurons glial cells olfactory bulb damaged lesions neurodegenerative diseases galectin1 8 9 neuroprotective antiinflammatory activities galectin3 facilitates proinflammatory action however also plays important role recovery period several ligand glycoconjugates identified far laminin integrins neural cell adhesion molecule l1 sulfatide neuropilin1 plexina4 receptor complex triggering receptor myeloid cells 2 t cell immunoglobulin mucin domain nglycan branching lymphocytes oligodendroglial progenitors mediated 1 6nacetylglucosaminyltransferase v mgat5 gntv influences galectinbinding modulating inflammatory responses remyelination neurodegenerative diseases desulfated galactosaminoglycans keratan sulfate potential ligands galectins especially galectin3 regulating neural regeneration galectins multitudinous functions depending cell type context well posttranslational modifications including oxidization phosphorylation snitrosylation cleavage certain rules expression patterns galectins ligand glycoconjugates possibly related glucose metabolism cellspmid34720894 pmcpmc8554236 doi103389 fnana2021767330,1.0
trifluoperazine reduces cuprizoneinduced demyelination via targeting nrf2 ikb mice eur j pharmacol 2021 aug 17174432 doi 101016 jejphar2021174432 online ahead printabstractmultiple sclerosis ms one common neurodegenerative diseases disease immune system attacks oligodendrocyte cells myelin sheath myelinated neurons central nervous system causing destruction conditions lead impaired conduction nerve impulses manifested symptoms weakness fatigue visual motor disorders study aimed evaluate ability trifluoperazine tf improve cuprizoneinduced behavioral histopathological changes prefrontal cortex c57bl 6 male mice demyelination induced adding 02 cuprizone cpz standard animal diet 6 weeks three doses tf 05 1 2 mg kg day ip given daily last 2 weeks treatment treatment cpz induced weight loss 6 weeks treatment compared control group reversed administration tf behavioral tests pole test rotarod performance test showed decrease motor coordination balance group treated cpz p 001 treatment tf last two weeks able improve motor deficiencies histopathological examination also evidenced increase demyelination cpz group improved tf administration addition cpz intake significantly decreased cerebral cortex levels pnrf2 p 0001 increased levels pikb p 0001 changes normalized tf groups tf administration also reversed increased levels nitrite reduced activity antioxidant enzyme superoxide dismutase associated cpz exposure tf can reduce harmful effects cpz reducing demyelination modulating nrf2 nfkb signaling pathwayspmid34416238 doi101016 jejphar2021174432,1.0
accelerating quantitative susceptibility r2 mapping using incoherent undersampling deep neural network reconstruction neuroimage 2021 jul 16118404 doi 101016 jneuroimage2021118404 online ahead printabstractquantitative susceptibility mapping qsm r2 mapping mri postprocessing methods quantify tissue magnetic susceptibility transverse relaxation rate distributions however qsm r2 acquisitions relatively slow even parallel imaging incoherent undersampling compressed sensing reconstruction techniques used accelerate traditional magnitudebased mri acquisitions however recover full phase signal required qsm due nonconvex nature study learningbased deep complex residual network dcrnet proposed recover magnitude phase images incoherently undersampled data enabling high acceleration qsm r2 acquisition magnitude phase r2 qsm results dcrnet compared two iterative one deep learning methods retrospectively undersampled acquisitions six healthy volunteers one intracranial hemorrhage one multiple sclerosis patients well one prospectively undersampled healthy subject using 7t scanner peak signal noise ratio psnr structural similarity ssim rootmeansquared error rmse regionofinterest susceptibility r2 measurements reported numerical comparisons proposed dcrnet method substantially reduced artifacts blurring compared methods resulted highest psnr ssim rmse magnitude r2 local field susceptibility maps compared two iterative one deep learning methods dcrnet method demonstrated 32 91 accuracy improvement deep grey matter susceptibility accelerated factor four dcrnet also dramatically shortened reconstruction time single 2d brain images 36140 seconds using conventional approaches 1570 millisecondspmid34280526 doi101016 jneuroimage2021118404,0.0
medroxyprogesterone acetate attenuates demyelination modulating microglia activation cuprizone neurotoxic demyelinating mouse model j neurodegener dis 2021 oct 15 10 5 5768 ecollection 2021abstractclinical data reported reduction multiple sclerosis ms symptoms pregnancy progesterone levels high medroxyprogesterone acetate mpa synthetic progestin contraceptive unknown neuroprotective effects study investigated effect contraceptive dose mpa microglia polarization neuroinflammation neurotoxic cuprizone cpz induced demyelinating mouse model ms mice received 1 mg mpa weekly achieving similar serum concentrations human contraceptive users results revealed mpa therapy significantly reduced demyelination corpus callosum addition mpa treatment induced significant reduction microglia m1markers inos il1 tnf m2markers arg1 il10 tgf significantly increased moreover mpa resulted significant decrease number inos positive cells m1 whereas trem2 positive cells m2 significantly increased furthermore mpa decreased protein expression levels nfb nlrp3 inflammasome well mrna expression levels downstream product il18 summary mpa reduces level demyelination antiinflammatory role cns demyelination inducing m2 microglia polarization suppressing m1 phenotype inhibition nfb nlrp3 inflammasome results suggest mpa suitable contraceptive pharmacological agent demyelinating diseasespmid34824899 pmcpmc8610806,1.0
humoral immune response convalescent covid19 people multiple sclerosis treated highefficacy diseasemodifying therapies multicenter casecontrol study j neuroimmunol 2021 aug 16 359577696 doi 101016 jjneuroim2021577696 online ahead printabstractaim determine influence highefficacy disease modifying therapy dmt development igg sarscov2 antibody response covid19 convalescent people multiple sclerosis pwms methods seventyfour pwms taking highefficacy dmts specifically natalizumab fingolimod alemtuzumab ocrelizumab cladribine ublituximab diagnosed covid19 44 healthy persons hc enrolled sarscov2 antibodies tested elecsys antisarscov2 s assayresults pwms taking highefficacy dmts significantly higher chance negative titer sarscov2 antibodies compared healthy controls 33 negative pwms 446 compared one negative hc 23 p 0001 pwms taking bcell depleting therapy ocrelizumab ublituximab significantly higher chance negative titer sarscov2 antibodies compared pwms dmts 29 negative pwms bcell therapy 644 compared four negative pwms dmts 138 p 0001 dmts two 333 pwms taking fingolimod two 167 pwms taking cladribine failed develop igg sarscov2 antibodies bcell depleting therapy independently predicted negative titer igg sarscov2 antibody exp b 0014 95ci 00020110 p 0001 conclusions significant proportion convalescent covid19 pwms highefficacy dmts will develop igg sarscov2 antibodies bcell depleting therapies independently predict negative low titer igg sarscov2 antibodypmid34418815 doi101016 jjneuroim2021577696,0.0
burden multiple sclerosis iran 1990 2017 background multiple sclerosis ms burdensome chronic autoimmune disease central nervous system aimed report incidence prevalence mortality disability adjusted life years dalys ms iran national level different age sex groups period 28 years 19902017 methodsdata extracted global burden disease study gbd 1990 2017 published institute health metrics evaluation incidence dalys prevalence ms estimated report burden ms based sex age iran 1990 2017resultsat national level agestandardized incidence rate asir agestandardized prevalence rate aspr agestandardized dalys rate asdr agestandardized mortality rate asmr iran 2017 24 95 uncertainty interval ui 21 27 695 621 778 291 236 347 04 03 04 per 100 000 population respectively period 1990 2017 measures increased higher among females incidence rate began upward trend age 20 attained highest level age 25conclusionin iran agestandardized ms rates increasing 28 years 1990 2017 findings can help policy makers health planners design communicate plans better resource allocation depending incidence prevalence growing numbers ms patients iran,0.0
frequency raynauds phenomenon early diagnosis systemic sclerosis systemic sclerosis large veteran health administration database background describe raynauds phenomenon rp potential early diagnosis systemic sclerosis vedoss systemic sclerosis ssc veterans deployed support post9 11 operations sought describe military occupation specialty clinical features vasodilator use across three diagnosesmethodsindividual veterans medical records assessed rp icd94430 vedoss swelling hands icd972981 rp icd94430 ssc icd97101 distribution sociodemographic military service branch job classification vasodilator use comorbidities examined across three classifications disease chisquared test fishers exact compared frequency categorical variables logistic regression assessed likelihood characteristics three classificationsresultsin population 607 665 individual veteran medical records 857 rp 45 met possible vedoss criteria 71 diagnosis ssc majority rp potential vedoss ssc cases white males craftworks engineering maintenance healthcare greater likelihood rp less half rp vedoss patients vasodilators common comorbidities population diagnostic code pain highest potential vedoss group 816 followed depression groupsconclusionthis unique veteran population predominatelymale patients data suggests vasodilator medications potentially underutilized rp potential vedoss data highlights mood pain management important aspect ssc care,0.0
setipiprant androgenetic alopecia males results randomized doubleblind placebocontrolled phase 2a trial clin cosmet investig dermatol 2021 oct 15 1415071517 doi 102147 ccids319676 ecollection 2021abstractpurpose evaluate oral setipiprant versus placebo scalp hair growth men androgenetic alopecia aga patients methods males aged 18 49 years aga enrolled doubleblind multicenter 32week phase 2a trial randomized twicedaily bid 1000mg 2500 mg total daily dose 2000 mg setipiprant tablets placebo 24 weeks assessed weeks 4 8 16 24 week 32 followup study initially included finasteride 1mg oncedaily group removed protocol amendment changes baseline week 24 target area hair count tahc blinded subject selfassessment ssa target area photographs coprimary efficacy endpoints hair growth also evaluated using blinded investigator global assessment iga safety assessments included adverse events aes clinical laboratory tests analysis covariance models used test statistical significance tahc ssa iga data summarized without statistical analysis finasterideresults randomized subjects n169 included 74 placebo 83 setipiprant 12 finasteride subjects 117 692 113 669 subjects completed week 24 32 visits respectively treatment groups similar baseline characteristics neither coprimary efficacy endpoint met week 24 tahc ssa findings indicated hair growth improvements setipiprant versus placebo setipiprant also improve hair growth versus placebo per iga treatmentrelated aes mild moderate severity occurred 123 259 250 placebo setipiprant finasteride groups respectively two treatmentemergent serious aes tesaes cellulitis multiple sclerosis reported placebo group unrelated treatment tesaes reported setipiprant finasterideconclusion setipiprant 1000 mg bid safe well tolerated demonstrate efficacy versus placebo scalp hair growth men agapmid34703265 pmcpmc8526366 doi102147 ccids319676,0.0
wearingoff symptoms standard extended natalizumab dosing intervals experiences covid19 pandemic j neurol sci 2021 aug 22 429117622 doi 101016 jjns2021117622 online ahead printabstractnatalizumab effectively prevents disease activity relapsingremitting multiple sclerosis many treated patients report subjective wearingoff symptoms end 4week interval infusions extended interval dosing eid promising strategy mitigate risk natalizumabassociated progressive multifocal leukoencephalopathy unknown whether eid affects wearingoff symptoms observational study evaluated prevalence intensity wearingoff symptoms changed natalizumab dosing intervals extended 4 6 weeks 30 treated patients outbreak covid19 norway new increased wearingoff symptoms eid reported 50 symptom increase frequent among patients preexisting wearingoff symptoms standard dosing compared patients without preexisting symptoms p 00005 observations support need study effect eid wearingoff symptoms randomized controlled trialspmid34474301 doi101016 jjns2021117622,0.0
multiomic study skin peripheral blood serum serum proteome reflection disease process endorgan level systemic sclerosis background serum proteins can readily assessed routine clinical care however unclear extent serum proteins reflect molecular dysregulations peripheral blood cells pbcs affected endorgans systemic sclerosis ssc conducted multiomic comparative analysis ssc serum profile pbc skin gene expression concurrently collected samplesmethodsglobal gene expression profiling carried skin pbc samples obtained 49 ssc patients enrolled genisos observational cohort 25 unaffected controls levels 911 proteins determined olink proximity extension assay concurrently collected serum samplesresultsboth ssc pbc skin transcriptomes showed prominent type interferon signature examination ssc serum profile revealed upregulation proteins involved profibrotic homing extravasation well extracellular matrix components modulators notably several soluble receptor proteins egfr erbb2 erbb3 vegfr2 tgfbr3 pdgfr downregulated thirtynine proteins correlated severity ssc skin disease differential expression serum protein ssc vs control comparison significantly correlated differential expression corresponding transcripts skin pbcs moreover differentially expressed serum proteins significantly connected wellassociatedproteins skin pbc gene expression dataset assessment concordance betweensample similarities revealed molecular profile serum proteins skin gene expression data significantly concordant patients ssc healthy controlsconclusionsssc serum protein profile shows upregulation profibrotic cytokines downregulation soluble egf key receptors multilevel comparative analysis indicates serum protein profile ssc correlates closely molecular dysregulations skin pbcs might serve reflection disease severity endorgan level,0.0
neurofilament light possible prognostic biomarker treatment vascular contributions cognitive impairment dementia background decreased cerebral blood flow systemic inflammation heart failure hf increase risk vascular contributions cognitive impairment dementia vcid alzheimer diseaserelated dementias adrd previously demonstrated pna5 novel glycosylated angiotensin 17 ang 17 mas receptor masr agonist peptide effective therapy rescue cognitive impairment preclinical model vcid neurofilament light nfl protein concentration correlated cognitive impairment elevated neurodegenerative diseases hypoxic brain injury cardiac disease goal present study determine 1 treatment ang 17 masr agonists can rescue cognitive impairment decrease vcidinduced increases nfl levels compared hfsaline treated mice 2 nfl levels correlate measures cognitive function brain cytokines vcid modelmethodsvcid induced c57bl 6 male mice via myocardial infarction mi 5 weeks postmi mice treated daily subcutaneous injections 24 days 5 weeks mi pna5 angiotensin 17 500 microg kg day 50 microg kg day saline n 15 group following 24day treatment protocol cognitive function assessed using novel object recognition test cardiac function measured echocardiography plasma concentrations nfl quantified using quanterix simoa assay brain circulating cytokine levels determined milliplex map mouse high sensitivity multiplex immunoassay treatment groups compared via anova significance set p 005resultstreatment ang 17 masr agonists reversed vcidinduced cognitive impairment significantly decreased nfl levels mouse model vcid compared hfsaline treated mice nfl levels significantly negatively correlated cognitive scores concentrations multiple pleiotropic cytokines brainconclusionsthese data show treatment ang 17 masr agonists rescues cognitive impairment decreases plasma nfl relative hfsalinetreated animals vcid mouse model levels nfl significantly negatively correlated cognitive function several brain cytokine concentrations based preclinical findings propose circulating nfl might candidate prognostic biomarker vcid may also serve pharmacodynamic response biomarker therapeutic target engagement,0.0
prognostic utility igm oligoclonal bands myelin lipids multiple sclerosis j neuroimmunol 2021 aug 21 359577698 doi 101016 jjneuroim2021577698 online ahead printabstractigm oligoclonal bands ocmbs myelinspecific lipids identified marker poor prognosis multiple sclerosis ms aim examine relation lipidspecific ocmbs lsocmbs evolution ms analytical ambispective individualbased study conducted selected 116 patients 95 lsocmbs predominant lipid recognized phosphatidylcholine positive gangliosides ocmb group reached better scores 9hpt phosphatidylcholine sphingolipids phosphatidylethanolamine ocmb groups showed statistical differences magnetic resonance parameters conclusion lsocmbs showed statistically significant differences functional imaging testspmid34450374 doi101016 jjneuroim2021577698,1.0
assessment fingolimod versus dimethyl fumarate treatment multiple sclerosis 24month followup study background oral treatment multiple sclerosis ms using diseasemodifying therapies dmts challenge worldwide fingolimod fty dimethyl fumarate dmf two approved agents oral treatment ms remarkable efficacy relapse control deceleration disability progression therefore current study done compare disability control lesions magnetic resonance imaging mri adverse effects patients treated fty dmfmethods randomized clinical trial irmuirec13963786 conducted 60 patients randomly divided two groups treatment 05 mg daily dose fty n 30 240 mg dose dmf twice daily n 30 disability patients assessed using expanded disability status scale edss within 6 weeks 12 24 months following treatment initiation mri performed patients prior study initiation within 24 months obtained data compared two study groupsresults significant difference two treatment groups based edss scores brain lesions mri newly formed plaques p005 skin gastrointestinalrelated complaints common adverse effects dmf increase liver enzyme level thrombocytopenia common complications fty respectively pvalue 022 conclusion according findings within 24month followup dmf neither superior inferior fty comparing mri lesions edss scores adverse effects although evaluations larger sample size recommendedkeywords fingolimod dimethyl fumarate multiple sclerosis,0.0
multiple sclerosis care units latin america consensus recommendations objectives functioning implementation j neurol sci 2021 sep 8 429118072 doi 101016 jjns2021118072 online ahead printabstractobjective currently several reasons promote worldwide concept multiple sclerosis care units mscu better management affected patients ideally mscu human technical resources distinguish improve care affected patients however local regional aspects considered recommending units operate objective consensus recommendations review mscu work latin america improve longterm outcomes ms patientsmethods panel neurology experts latin america dedicated diagnosis care ms patients gathered virtually 2019 2020 carry consensus recommendation objectives functioning implementation mscu latin america achieve consensus methodology formal consensusrand ucla method usedresults recommendations focused objectives human technical resources general functioning mscu latin americaconclusions recommendations consensus guidelines attempt optimize health care management ms patients setting mscu work regionpmid34509134 doi101016 jjns2021118072,0.0
covid19 infection hospitalization rate iranian multiple sclerosis patients know may 2021 abstractbackground despite investigations effect disease modifying therapies dmts used multiple sclerosis ms coronavirus disease 2019 covid19 still controversiesobjective designed study evaluate epidemiological features covid19 large sample people ms pwms isfahan iran well association dmts risk covid19 infection hospitalizationmethods observational pwms interviewed subjects ms covid19 historyresults 3050 subjects included 74 female mean age 4136 423 138 confirmed covid19 shows pwms higher risk infection compared general population significant relationship observed covid19 infection individual drugs dimethyl fumarate rituximab lowest highest relative risks hospitalization rate compared drugs respectivelyconclusion found evidence supporting higher prevalence covid19 pwms compared general population however results show pwms prone hospitalization compared general population therefore advised use safer treatment possible complete vaccination postpone use rituximab,0.0
molecular mri neuroinflammation time overcome translational roadblock neuroscience 2021 aug 24s03064522 21 004231 doi 101016 jneuroscience202108016 online ahead printabstractthe ability detect molecular target central nervous system noninvasively high spatial resolution using magnetic resonance imaging mri attracted interest researchers several decades yet molecular mri studies remain restricted preclinical stage path clinical translation remains unclear focus molecular mri neuroinflammation moved parenchymal vascular targets easily reachable intravenously injected probes allowed use large superparamagnetic probes microsized particles iron oxide mpio dramatically improved sensitivity molecular mri compared smaller contrast agents particular recent studies demonstrated feasibility unraveling inflammation brain mri using mpio able bind activated endothelial cells potential applications neurovascular neuroinflammatory neurodegenerative disorders present review present striking advances field remaining challenges must overcome clinical use molecular mri neuroinflammationpmid34450211 doi101016 jneuroscience202108016,0.0
adverse events reported iranian patients multiple sclerosis first dose sinopharm bbibpcorv vaccine 2021 sep 23s0264410x 21 012214 doi 101016 jvaccine202109030 online ahead printabstractms patients one first populations vaccinated iran date used vaccine brand iranian ms patients sinopharm covid19 vaccine first study adverse events first dose sinopharm vaccine 583 iranian ms patients google form link sent ms patients social networks may 1 2021 may 22 2021 serious adverse event reported least one complaint mostly transient reported 350 60 vaccine recipients constitutional symptoms malaise fatigue fever shivering generalized body pain 51 headache 9 reported complaints found relation gender prior infection covid19 reported symptoms p value less 005 five recipients 09 reported ms relapse vaccination ms worsening minor incident related feverpmid34579974 doi101016 jvaccine202109030,0.0
changing firing threshold normal optic nerve axons application infrared laser light sci rep 2021 oct 15 11 1 20528 doi 101038 s41598021000841abstractnormal optic nerve axons exhibit temperature dependence previously explained membrane potential hyperpolarization warming now report near infrared laser light delivered via fibre optic light guide also affects axonal membrane potential threshold least partly photothermal effect application light optic nerve recording site gave rise local membrane potential hyperpolarization period minute increased size depolarizing potential application near site electrical stimulation reversibly raised currentthreshold change threshold recorded minutes irradiation significantly increased application ih blocker zd7288 50 m indicating ih limits hyperpolarizing effect light light application also fast effects nerve behaviour increasing threshold without appreciable delay within seconds probably mechanism independent kinetically fast k+ channels na+ channel inactivation hypothesized caused reversible changes myelin functionpmid34654844 doi101038 s41598021000841,1.0
facilitators barriers regulation medical cannabis scoping review peerreviewed literature background recent decades several political legislative judicial consumer commercial processes around world advanced legalization efforts use medical cannabis mc use mc evolves legislative reform increase public acceptance therapeutic potential need exists investigate facilitators barriers mc regulationmethodsa scoping review conducted identify facilitators barriers associated implementation mc regulations medline embase amed psycinfo databases systematically searched restrictions placed geographic location jurisdiction eligible articles included evaluated mc regulatory framework one countriesresultstwentytwo articles deemed eligible included review themes identified include 1 effects conflicts mindset ideology state population 2 use comparisons analyze mc regulation 3 need knowledge advice empirical clinical evidence inform future mc policiesconclusionpolicymakers aware facilitators mc regulation implementation process influence state federal congruence increased transparency incorporation stakeholder concerns order effectively respond growing societal acceptance mc use among patients given comprehensive understanding influential factors policymakers may better equipped meet consumer commercial demands rapidly evolving mc regulatory environment,0.0
novel vitro experimental approaches study myelination remyelination central nervous system front cell neurosci 2021 oct 14 15748849 doi 103389 fncel2021748849 ecollection 2021abstractmyelin lipidic insulating structure enwrapping axons allowing fast saltatory nerve conduction central nervous system myelin sheath result complex packaging multilamellar extensions oligodendrocyte ol membranes reaching myelinating capabilities ols undergo precise program differentiation maturation starts ol precursor cells opcs last 20 years biology opcs behavior pathological conditions studied several experimental models cocultured neurons opcs undergo terminal maturation produce myelin tracts around axons allowing investigate myelination response exogenous stimuli simple vitro system hand vivo models closely reproducing features human pathophysiology enabled assess consequences demyelination molecular mechanisms remyelination often used validate effect pharmacological agents however complex suitable large scale drug discovery screening recent advances cell reprogramming biophysics bioengineering allowed impressive improvements methodological approaches study brain physiology myelination rat mouse opcs can replaced human opcs obtained induced pluripotent stem cells ipscs derived healthy diseased individuals thus offering unprecedented possibilities personalized disease modeling treatment opcs neural cells can also artificially assembled using 3dprinted culture chambers biomaterial scaffolds allow modeling celltocell interactions highly controlled manner interestingly scaffold stiffness can adopted reproduce mechanosensory properties assumed tissues physiological pathological conditions moreover recent development ipscderived 3d brain cultures called organoids made possible study key aspects embryonic brain development neuronal differentiation maturation network formation temporal dynamics inaccessible traditional vitro cultures despite huge potential organoids application myelination studies still infancy review shall summarize novel relevant experimental approaches implications identification remyelinating agents human diseases multiple sclerosispmid34720882 pmcpmc8551863 doi103389 fncel2021748849,1.0
walking common ground crossdisciplinary scoping review clinical utility digital mobility outcomes npj digit med 2021 oct 14 4 1 149 doi 101038 s41746021005135abstractphysical mobility essential health patients often rate highpriority clinical outcome digital mobility outcomes dmos realworld gait speed step count show promise clinical measures many medical conditions however current research nascent fragmented discipline scoping review maps existing evidence clinical utility dmos identifying commonalities across traditional disciplinary divides november 2019 11 databases searched records investigating validity responsiveness 34 dmos four diverse medical conditions parkinsons disease multiple sclerosis chronic obstructive pulmonary disease hip fracture searches yielded 19 672 unique records screening 855 records representing 775 studies included charted systematic maps studies frequently investigated gait speed 704 studies step length 307 cadence 214 daily step count 207 studied differences healthy pathological gait 364 associations dmos clinical measures 488 outcomes 43 responsiveness interventions 268 gait speed step length cadence step time step count exhibited consistent evidence validity responsiveness multiple conditions although evidence inconsistent lacking dmos dmos adopted mainstream tools work needed establish predictive validity responsiveness ecological validity crossdisciplinary efforts align methodology validate dmos may facilitate adoption clinical practicepmid34650191 doi101038 s41746021005135,0.0
inhibition rho kinase fasudil ameliorates cognition impairment app#x2f ps1 transgenic mice via modulation gut microbiota metabolites front aging neurosci 2021 oct 14 13755164 doi 103389 fnagi2021755164 ecollection 2021abstractbackground fasudil rho kinase inhibitor exerts therapeutic effects mouse model alzheimers disease ad chronic neurodegenerative disease progressive loss memory however mechanisms remain unclear addition gut microbiota metabolites implicated ad methods examined effect fasudil learning memory using morris watermaze mwm test appswe psen1de9 transgenic app ps1 mice 8 months old treated ip fasudil 25 mg kg day adf saline adns age gendermatched wildtype wt mice fecal metagenomics metabolites performed identify novel biomarkers ad elucidate mechanisms fasudil induced beneficial effects ad mice results mwm test showed significant improvement spatial memory app ps1 mice treated fasudil compared adns metagenomic analysis revealed abundance dominant phyla three groups including bacteroidetes 23744 firmicutes 64266 increased relative abundance ratio firmicutes bacteroidetes adns 591 compared wt 317 contrast firmicutes bacteroidetes ratio decreased wt level adf 328 lefse analysis metagenomics identified s_prevotella_sp_cag873 adf potential biomarker s_helicobacter_typhlonius s_helicobacter_sp_mit_031616 adns potential biomarkers metabolite analysis revealed increment various metabolites including glutamate hypoxanthine thymine hexanoylcoa leukotriene relative adns adf microbiota potential biomarkers mainly involved metabolism nucleotide lipids sugars inflammatory pathway conclusions memory deficit app ps1 mice correlated gut microbiome metabolite status fasudil reversed abnormal gut microbiota subsequently regulated related metabolisms normal ad mice believed fasudil can novel strategy treatment ad via remodeling gut microbiota metabolites novel results also provide valuable references use gut microbiota metabolites diagnostic biomarkers therapeutic targets clinical studies adpmid34721000 pmcpmc8551711 doi103389 fnagi2021755164,0.0
global gene expression analysis systemic sclerosis myofibroblasts demonstrates marked increase expression multiple nbpf genes sci rep 2021 oct 14 11 1 20435 doi 101038 s4159802199292yabstractmyofibroblasts key effector cells responsible exaggerated tissue fibrosis systemic sclerosis ssc despite importance ssc pathogenesis specific transcriptome ssc myofibroblasts described purpose study identify transcriptome differences ssc myofibroblasts nonmyofibroblastic cells alpha smooth muscle actin sma expressing myofibroblasts sma negative cells isolated employing laser capture microdissection dermal cell cultures four patients diffuse ssc recent onset total mrna extracted cell populations amplified analyzed employing microarrays results specific genes validated western blots immunohistochemistry transcriptome analysis revealed 97 differentially expressed transcripts ssc myofibroblasts compared nonmyofibroblasts annotation clustering ssc myofibroblastspecific transcripts failed show tgf signature represented transcripts corresponded several different genes neuroblastoma breakpoint family nbpf genes nbpf genes highly expanded humans present murine rat genomes vitro studies employing cultured ssc dermal fibroblasts immunohistochemistry affected ssc skin confirmed increased nbpf expression ssc results indicate ssc myofibroblasts represent unique cell lineage expressing specific transcriptome includes high levels transcripts corresponding numerous nbpf genes elevated expression nbpf genes ssc myofibroblasts suggests nbpf gene products may play role ssc pathogenesis may represent novel therapeutic targetpmid34650102 doi101038 s4159802199292y,0.0
quantifying relationship disability progression quality life patients treated nmosd insights sakura studies abstractbackgroundto date specific scales developed explore impact neuromyelitis optica spectrum disorder nmosd related disability quality life qol expanded disability status scale edss euroqol 5dimensions eq5d used assess disability qol respectively patients nmosd however limited evidence surrounding use condition compared edss eq5d data across two clinical trials quantify relationship disability qol patients nmosdmethodssakurasky nct02028884 sakurastar nct02073279 phase 3 multicenter randomized international doubleblind placebocontrolled parallelassignment studies satralizumab administered combination baseline immunosuppressants sakurasky monotherapy sakurastar edss eq5d assessed baseline 24week intervals thereafter relationship disability qol assessed estimating eq5d utilities uk tariff incremental edss category repeatedmeasures linear model used regress health utilities edss scorederived health statesresultsoverall 176 patients underwent least one edss assessment completed eq5d survey included analysis clear association mean eq5d score edss score decreases qol observed incremental increase disability relationship edss eq5d score remained consistent across different treatment groupsconclusionsthese results generated highquality clinical trial data demonstrated strong consistent relationship disability qol patients nmosd,0.0
caracterizacin epidemiolgica clnica e imagenolgica de pacientes con esclerosis mltiple introductionmultiple sclerosis demyelinating degenerative chronic autoimmune inflammatory disease affects central nervous system condition leading cause neurological disability young adultsobjectiveto characterize patients diagnosis multiple sclerosis admitted neurology service arnaldo milin castro clinical surgical university hospitalmethodsa descriptive crosssectional study carried patients diagnosis multiple sclerosis admitted neurology service arnaldo milin castro clinical surgical university hospital santa clara villa clara january 2018 december 2019 study population consisted 30 patientsresultsthe average age debut 387 years ratio patients white nonwhite skin color 9 1 women men 14 1 relapsingremitting multiple sclerosis accounted 70 minimum degree disability 60 4827 4137 3793 patients supratentorial infratentorial lesions two four number respectivelyconclusionsfemale gender predominated age debut 20 29 years motor sensory cerebellar alterations common symptoms relapsingremitting multiple sclerosis predominant clinical presentation minimal degree disability supratentorial infratentorial lesions number lesions number two four frequent cases change intensity corpus callosummesh multiple sclerosis epidemiology demyelinating diseases,1.0
patterns correlates sedentary behaviour among people multiple sclerosis crosssectional study sci rep 2021 oct 13 11 1 20346 doi 101038 s4159802199631zabstracthigh levels sedentary behaviour associated poor health outcomes people multiple sclerosis ms identifying modifiable correlates sedentary behaviour people ms essential design effective intervention strategies minimise sedentary time study aimed quantify patterns identify correlates sedentary behaviour among adults ms fatigue selfefficacy walking capability physical psychological impact ms healthrelated quality life participation autonomy assessed questionnaire participants wore activpal monitor total min day prolonged bouts 30 min breaks sedentary time calculated associations examined using regression analysis adjusted demographic clinical confounders fiftysix adults ms participated mean sd age 570 925 years 66 female selfefficacy control ms associated sedentary time 016 95 ci 001 030 selfefficacy function maintenance 002 95 ci 000 004 healthrelated quality life euroqol5d 3160 95 ci 725 5596 autonomy indoors subscale impact participation autonomy questionnaire 511 95 ci 974 0485 associated breaks sedentary time future studies consider selfefficacy healthrelated quality life participation autonomy potential components interventions reduce sedentary behaviourpmid34645876 doi101038 s4159802199631z,0.0
durability evidence disease activity3 neda3 patients receiving cladribine tablets clarity extension study abstractbackgroundno evidence disease activity neda3 patientcentric outcome increasingly used goal multiple sclerosis treatmentobjectivedetermine treatment durability cladribine tablets beyond 2years considering variable bridging interval 011160weeks clarity clarity extensionmethodsbetween clarity clarity extension patients transitioned cladribine tablets 35mg kg placebo cp35 group n98 continued treatment cladribine tablets 35mg kg cc70 group n186 treatment assignment randomized blinded clarity clarity extensionresultsthe 2year neda3 clarity extension encompassing years clarity extension 296 cp35 group 328 cc70 group evidence treatment effect differed varying bridging intervals patients cp35 group bridging interval 48weeks 1year neda3 first year clarity extension 444 28 63 compared 314 11 35 patients bridging interval 48weeksconclusiontreatment cladribine tablets clarity followed either placebo cladribine tablets clarity extension produced sustained benefits neda3 constituent elements follow period 6years clarity baseline,0.0
critical role astrocyte nad+ glycohydrolase myelin injury regeneration westernstyle diets cause disruptions myelinating cells astrocytes within mouse central nervous system cns cd38 shows increased expression cuprizone experimental autoimmune encephalomyelitis models demyelination addition cd38 main nicotinamide adenine dinucleotide nad+ depleting enzyme cns altered nad+ metabolism linked high fat consumption multiple sclerosis ms identify increased cd38 expression male mouse spinal cord following chronic high fat consumption focal toxin lysolecithin ll mediated demyelinating injury reactive astrocytes within active ms lesions demonstrate cd38catalytically inactive mice substantially protected high fatinduced nad+ depletion oligodendrocyte loss oxidative damage astrogliosis cd38 inhibitor 78c increased nad+ attenuated neuroinflammatory changes induced saturated fat applied astrocyte cultures conditioned media saturated fatexposed astrocytes applied oligodendrocyte cultures impaired myelin protein production suggesting astrocytedriven indirect mechanisms oligodendrogliopathy cerebellar organotypic slice cultures subject ll demyelination saturated fat impaired signs remyelination effects mitigated concomitant 78c treatment significantly oral 78c increased counts oligodendrocytes remyelinated axons focal llinduced spinal cord demyelination using ribotag approach identified unique vivo brain astrocyte translatome profile induced 78cmediated cd38 inhibition mice including decreased expression proinflammatory astrocyte markers increased growth factors findings suggest high fat diet impairs oligodendrocyte survival differentiation astrocytelinked mechanisms mediated nad+ase cd38 highlight cd38 inhibitors potential therapeutic candidates improve myelin regenerationsignificance statementmyelin disturbances oligodendrocyte loss can leave axons vulnerable leading permanent neurologic deficits results study suggest metabolic disturbances triggered consumption diet high fat promote oligodendrogliopathy impair myelin regeneration astrocytelinked indirect nad+dependent mechanisms demonstrate restoring nicotinamide adenine dinucleotide nad+ levels via genetic inactivation cd38 can overcome effects moreover show therapeutic inactivation cd38 can enhance myelin regeneration together findings point new metabolic targeting strategy positioned improve disease course multiple sclerosis conditions integrity myelin key concern,1.0
radiological laboratory features multiple sclerosis patients immunosuppressive therapy multicenter retrospective study japan front neurol 2021 oct 13 12749406 doi 103389 fneur2021749406 ecollection 2021abstractbackground multiple sclerosis ms relapsing inflammatory demyelinating disease central nervous system showing marked clinical heterogeneity many factors might influence choice relapse prevention drug treatment response varies among patients despite enlargement diseasemodifying drugs ms msdmds patients treated corticosteroid immunosuppressant cs objective clarify radiological laboratory features ms treated cs relapse prevention methods clinical records including radiological laboratory findings drugs used relapse prevention reviewed retrospectively results 92 consecutive ms patients 25 27 treated cs followings observed less frequently patients treated cs msdmds three periventricular lesions ovoid lesions subcortical lesions typical contrastenhancing lesions negative serum autoantibodies positive oligoclonal bands cerebrospinal fluid multiple logistic regression analysis revealed absence typical contrastenhancing lesions positivity serum autoantibodies independent factors associated cs prescription odds ratio 25027 14537 respectively conclusion cohort japanese patients clinically diagnosed ms radiological serological findings atypical ms observed frequently patients treated cs msdmds part ms therapy absence contrastenhancing lesions typical ms positivity serum autoantibodies independent factors strongly associated cs usepmid34721276 pmcpmc8548818 doi103389 fneur2021749406,1.0
fouryear safety effectiveness data patients multiple sclerosis treated fingolimod spanish gilenya registry plos one 2021 oct 13 16 10 e0258437 doi 101371 journalpone0258437 ecollection 2021abstractobjective describe profile patients multiple sclerosis ms treated fingolimod spain assess effectiveness safety fingolimod 4 years inclusion spanish gilenya registrymethods observational retrospective prospective multicenter case registry including patients relapsingremitting ms rrms starting treatment fingolimod 43 centers spain analyses performed overall population subgroups according prior diseasemodifying therapy dmt glatiramer acetate interferon beta1 brace natalizumab treatment naveresults six hundred sixtysix evaluable patients included 911 previously treated least one dmt mean annualized relapse rate arr prior fingolimod 112 mean edss fingolimod initiation 303 fingolimod reduced arr 714 75 755 803 1 2 3 4 years respectively p0001 significant reduction arr continued observed subgroups 4 years edss showed minimal deterioration edss scores year 1 year 4 remaining mostly stable percentage patients without t1 gd+ lesions progressively increased 456 year prior fingolimod initiation 882 year 4 proportion patients free new enlarged t2 lesions 4 years fingolimod treatment 803 trend radiological measures also observed subgroups adverse events aes experienced 416 patients commonly lymphopenia 125 urinary tract infection 37 aes mild severity 36 patients serious aesconclusions patient profile similar observational studies results obtained longterm use fingolimod showed effective regardless prior dmt adequate safety results positive benefitrisk balancepmid34644366 doi101371 journalpone0258437,0.0
neuroimmune multihit perspective coronaviral infection abstractit well accepted environmental stressors experienced ones life microbial infections chemical toxicants even psychological stressors ultimately shape central nervous system cns functioning can also contribute eventual breakdown severity timing type environmental hits woven together genetic factors likely determine cns outcomes become apparent focused review assesses current covid19 pandemic lens multihit framework disuses sarscov2 virus causative agent might impact brain potentially interact environmental insults longterm consequences sar2 cov2 upon neuronal processes yet unclear emerging evidence suggesting possibility microglial inflammatory factors potentially contributing neurodegenerative illnesses finally critical consider impact virus context substantial psychosocial stress associated global pandemic indeed loneliness fear future loss social support alone exerted massive impact upon individuals especially vulnerable young elderly substantial upswing depression anxiety eating disorders evidence years come might matched similar spike dementia well motor cognitive neurodegenerative diseases,0.0
sarscov2 vaccination multiple sclerosis clearer picture time point cd20 depleting therapy ongoing coronavirus disease 2019 covid19 one deadliest pandemics history associated significant considerations people living multiple sclerosis plwms interest motivated knowing viral infections triggers disease exacerbation 1 chronic inflammatory demyelinating disorder central nervous system cns relapses associated infectious stimuli lead prolonged severe clinical worsening spontaneous relapses 2 moreover plwms higher risk infections increased need extended stay intensive care unit 3 likelihood infections increases immunomodulatory immunosuppressive agents required adequate disease control many patients admittedly impact covid19 disease reactivation ms still investigation however recent pooled analysis 18 observational studies comprising 5634 pwms provides first evidence assumption plwms vulnerable group severe acute respiratory syndrome coronavirus type 2 sarscov2 infection 4 study revealed 24 higher risk death observation requires confirmation prospective trialsmoreover study 125 plwms twothirds developed humoral immunity level considered protective covid19 5 notably chance developing sarscov2 antibodies halved treatment immunosuppressive therapies particularly anticd20 monoclonal antibodies rituximab ocrelizumab points mentioned spearheads considerations effective infection prevention employing vaccination sarscov2 plwmsin issue ebiomedicine sormani et al report first results largescale study conducted across 35 ms centers italy mrna vaccines bnt162b2 biontech pfizer 762 mrna1273 moderna 238 6 postvaccination sarscov2 antibodies detected 677 individuals 868 multivariable analysis antibody levels ocrelizumab 201fold decrease p0001 fingolimod 26fold reduction p 0001 rituximab treatment 20fold reduction p0001 significantly lower compared patients without diseasemodifying drug dmd furthermore antibody titers ocrelizumab rituximab given iv sixmonth intervals correlated time since last infusion rituximab longer intervals mean 386 days ocrelizumab mean 386 129 days respectively thus authors propose time point 143 days last infusion turning point sufficient humoral immune response mounted interestingly use mrna1273 vaccine showed systematically 325fold higher antibody levels bnt162b2 vaccine indicating differences immunogenicity two mrna vaccine preparations none cohort treatment ofatumumab cd20 depleting monoclonal antibody iven subcutaneously 4week intervals prolongation administration periods may required mount effective immune response treatment dmda key issue whether lower waning antibody levels also yield severe breakthrough infections seems clear neutralizing antibodies sarscov2 vaccination correlates well protective immunity cutoff antibodybased sarscov2 threshold remains established 7 addition ocrelizumab depletes circulating b cells within two weeks treatment sparing cd20negative plasma cells stem cells prob cells therefore resulting impairment antibody response shown study unexpected known nonlive vaccines 8 moreover humoral immune response one arm provide protective immune responses following vaccination early robust tcell responses present mild asymptomatic covid19 infection even absence antibodies ocrelizumabtreated plwms lower absent antibodies levels sarscov2 tcell responses vaccination bnt162b2 comparable healthy individuals 9 notably original pathogen challenges immune system broad spectrum antigens provides complex diverse immune response whereas vaccination likely induces narrower reaction might differences immunogenicity mrna vaccines related immunotherapy mode action vaccine vectorbased vaccines yielding even higher seropositivity rates antibody titers fingolimod treatment 10 fingolimod lipophilic s1p analog authors study mentioned discuss potential interaction mrna nanoparticles potentially lessening integrity immune response mrna vaccinesthe subsequent steps sormani et al commendable will try answer questions raised planned increase study cohort additional observational time points 6 18 months ideally heterologous boostering using another mrna vectorbased vaccine will demonstrate antibody levels develop longerterm remain protective plwms treated dmd,1.0
myelin imaging measures predictors cognitive impairment ms patients hybrid petmri study abstractbackgroundcognitive impairment one concerns multiple sclerosis ms related myelin loss different neuroimaging methods used quantify myelin relate cognitive dysfunctions among magnetization transfer ratio mtr diffusion tensor imaging dti recently positron emission tomography pet 11cpibobjectiveto investigate different myelin imaging modalities predictors cognitive dysfunctionmethodsfiftyone ms patients 24 healthy controls underwent clinical neuropsychological assessment mtr dti axial diffusionad fractional anisotropyfa maps 11cpib pet images pet mr hybrid systemresultsmtr dti fa differed patients without cognitive impairment association dti fa dti ad cognition psychomotor speed progressive ms 11cpib uptake mtr relapsingremitting ms mtr thalamus 051 p 0021 corpus callosum 024 p 0033 predictive cognitive impairment dtifa caudate 2693 p 0006 presented abnormal predictive resultconclusionlower myelin content 11cpib uptake associated worse cognitive status mtr predictive cognitive impairment ms,1.0
factors influencing degree disability patients multiple sclerosis front neurol 2021 oct 13 12714631 doi 103389 fneur2021714631 ecollection 2021abstractobjective explore factors influencing degree disability patients multiple sclerosis ms provide evidence early diagnosis prognostic evaluation clinical intervention methods retrospective observational study included 72 patients relapsingremitting multiple sclerosis rrms first hospital shanxi medical university patients completed craniocerebral spinal cord mri without gd enhancement evaluated expanded disability status score edss scores receiving treatment results among 72 patients rrms 45 625 edss score 3 total 27 patients 375 edss score 3 points univariate analysis showed age annual recurrence rate arr drug use albumin alb triglycerides tg total number lesions groups edss score 3 significantly different edss score 3 points p 005 multivariate logistic regression analysis showed alb total number lesions drug use independent influencing factors degree disability patients ms difference statistically significant p 005 roc curve constructed using alb total number lesions auc alb 0681 p 005 best cutoff value 442 g l sensitivity predict degree disability patients multiple sclerosis 852 specificity 511 auc total number lesions 0665 p 005 best cutoff value 55 sensitivity predict degree disability patients multiple sclerosis 704 specificity 644 auc combined alb total number lesions drug use 0795 p 005 sensitivity 778 specificity 733 optimal diagnostic cutoff value regression equation edss score patients multiple sclerosis 0420 conclusion serum alb total number lesions drug use patients multiple sclerosis independent factors influencing degree disability findings provide clinical evidence prognostic evaluation early intervention patients multiple sclerosispmid34721257 pmcpmc8548829 doi103389 fneur2021714631,0.0
robogait mobile robotic platform human gait analysis clinical environments sensors basel 2021 oct 13 21 20 6786 doi 103390 s21206786abstractmobile robotic platforms made inroads rehabilitation area gait assistance devices rarely used human gait monitoring analysis integration mobile robots field offers potential develop multiple medical applications achieve new discoveries study proposes use mobile robotic platform based depth cameras perform analysis human gait practical scenarios aim prove validity robot applicability clinical settings mechanical software design system presented well design controllers lanekeeping personfollowing servoing systems accuracy system evaluation joint kinematics main gait descriptors validated comparison viconcertified system tests performed practical scenarios effectiveness lanekeeping algorithm evaluated clinical tests patients multiple sclerosis gave initial impression applicability instrument patients abnormal walking patterns results demonstrate system can perform gait analysis high accuracy curved sections paths knee joint affected occlusion deviation person camera reference system issue greatly improved adjusting servoing system following distance control strategy robot specifically designed analysis human gait frontal part participant allows one capture gait properly represents one major contributions study clinical practicepmid34695999 doi103390 s21206786,0.0
increased 2arachidonoylsnglycerol levels normalize cortical responses sound improve behaviors fmr1 ko mice background individuals fragile x syndrome fxs autism spectrum disorder asd exhibit array symptoms including sociability deficits increased anxiety hyperactivity sensory hyperexcitability unclear endocannabinoid ecb modulation can targeted alleviate neurophysiological abnormalities fxs behavioral research reveals benefits inhibiting cannabinoid cb receptor activation increasing endocannabinoid ligand levels hypothesize enhancement 2arachidonoylsnglycerol 2ag fragile x mental retardation 1 gene knockout fmr1 ko mice may reduce cortical hyperexcitability behavioral abnormalities observed fxsmethodsto test whether increase 2ag levels normalized cortical responses mouse model fxs animals subjected electroencephalography eeg recording behavioral assessment following treatment jzl184 irreversible inhibitor monoacylglycerol lipase magl assessment 2ag performed using lipidomic analysis conjunction various doses time points postadministration jzl184 baseline electrocortical activity evoked responses sound stimuli measured using 30channel multielectrode array mea adult male mice 4 h 1 day postintraperitoneal injection jzl184 vehicle behavior assessment done using open field elevated plus maze 4 h posttreatmentresultslipidomic analysis showed 8 mg kg jzl184 significantly increased levels 2ag auditory cortex fmr1 ko wt mice 4 h posttreatment compared vehicle controls eeg recordings revealed reduction abnormally enhanced baseline gammaband power fmr1 ko mice significantly improved evoked synchronization auditory stimuli gammaband range postjzl184 treatment jzl184 treatment also ameliorated anxietylike hyperactivity phenotypes fmr1 ko miceconclusionsoverall results indicate increasing 2ag levels may serve potential therapeutic approach normalize cortical responses improve behavioral outcomes fxs possibly asds,0.0
mindfulness meditation impact attentional control emotion dysregulation arch clin neuropsychol 2021 oct 13 36 7 12831290 doi 101093 arclin acab053abstractobjective theoretical models mindfulness meditation conceptualize cultivation focused attention regulation emotional states attitudinal foundations promote nonjudgment acceptance facilitate cognitive affective processing resulting improved brain health within scientific study mindfulness meditation outcomes assessing behavioral neural correlates attentional control emotion regulation examined malleability function engagement mindfulness practices review synthesizes results pilot trials examining preliminary effects mindfulness meditation metrics cognitive affective brain health older adults individuals multiple sclerosisconclusions promising support mindfulness meditation enhance attentional control reduce mindwandering reduce emotion dysregulation however wellpowered efficacy trials objective assessment mindfulness practice data needed provide causal comprehensive evidence supporting efficacy mindfulness meditation brain health inclusion independently derived validated brainbased signatures cognitive affective functioning can additionally enable parsimonious understanding mindfulness meditation can causally impact metrics functional structural integrity human brainpmid34651648 doi101093 arclin acab053,0.0
effects mechanisms mucmscs ovarian structure function naturally ageing c57 mice background ovaries core reproductive organs women critical maintaining normal reproductive function endocrine system stability ageing c57 mouse model used evaluate efficacy mechanism mouse umbilical cord mesenchymal stem cells mucmscs explore mechanism mucmscs promote antioxidant repair mouse granulosa cells mgcs resultseighteenmonthold c57 mice randomly divided model group treatment group time 2monthold c57 mice established young group 15 mice per group mice treatment group injected via tail vein gfplabelled mucmscs ovarian volume ageing c57 mice decreased follicles stage mucmsc transplantation mouse ovaries increased size follicles various stages observed cortex antral follicle counts increased serum e2 amh inhb levels mice treatment group significantly higher mice model control group p 005 mucmscs downregulated expression autophagyrelated gene lc3b apoptosisrelated genes bax caspase3 upregulated expression sod2 peroxidase gene prdx iv reduced apoptosis rates reactive oxygen species ros levels granulosa cellsconclusionsmucmscs play roles promoting repair ageing ovaries regulating immunity antiinflammatory responses pi3kakt signalling pathway,0.0
impact data remote measurement technology clinical practice healthcare professionals depression epilepsy multiple sclerosis survey background variety smartphone apps wearables available help patients monitor health support health care professionals hcps providing clinical care part radarcns consortium conducted research application wearables smartphone apps care people multiple sclerosis epilepsy depressionmethodswe conducted large online survey study explore experiences hcps working patients one conditions survey covered smartphone apps wearables used clinicians patients data technologies impacted respondents clinical practice survey conducted february 2019 march 2020 via webbased platform detailed statistical analysis performed answersresultsof 1009 survey responses hcps 1006 included analysis data cleaning smartphone apps used half responding hcps three quarters patients use smartphone apps wearable devices healthrelated purposes hcps widely believe data patients collect using devices impacts clinical practice subgroup analyses show views impact data different aspects clinical work varies according whether respondents use apps lesser extent according clinical setting job roleconclusionsuse smartphone apps widespread among hcps participating large european survey caring people epilepsy multiple sclerosis depression majority respondents indicate treat patients use wearables devices healthrelated purposes data devices impact clinical practice,0.0
rebound activity fingolimod cessation case control study abstractbackgroundthere increase number reports multiple sclerosis ms rebound activity ra usually defined severe disease reactivation natalizumab fingolimod withdrawal exceeds pretreatment baseline inflammatory activity frequency risk factors predict ra remain unknown fingolimod currently frequently prescribed disease modifying therapy ms argentina need determine possible predictors raobjectivesto identify risk factors developing ra fingolimod cessation describe ra characteristics management evolutionmethodsthe study multicenter retrospective casecontrol study patients ms discontinued fingolimod followed nine months discontinuation demographic clinical paraclinical data extracted including age gender ms phenotype reason discontinuation number relapses year prior suspension time treated fingolimod edss rebound mri findingsresults26 cases ra matched 11 patients without ra median time elapsed ra 50 days 68 showed worsening edss evaluation 3 months ra compared control group difference found terms age gender phenotype edss moment suspension reason discontinuation number relapses previous year time therapyconclusionin casecontrolled study risk factors identified predict ra fingolimod cessation controlled prospective better powered studies needed confirm findings,0.0
effect benson relaxation technique depression anxiety stress jordanian patients diagnosed multiple sclerosis crosssectional study depress res treat 2021 oct 13 20218300497 doi 101155 2021 8300497 ecollection 2021abstractdepression anxiety stress das common symptoms multiple sclerosis ms patients highly correlated poor quality life managing das among patients can improve quality life qol empowering improved autonomy selfcare independency ability perform daily activities study aimed examining effectiveness benson relaxation technique brt reducing das among patients diagnosed ms jordan quasiexperimental study 105 jordanian patients diagnosed multiple sclerosis tested intervention group 60 patients received brt control group 45 patients received normal treatment data collected january 2021 april 2021 using arabic version depression anxiety stress scale dass21 intervention group instructed perform brt two times day 10 minutes home eight weeks two specific times 78hour intervals episode strobe guidelines followed reporting review baseline comparison statistical difference interventional control groups regard das levels das two groups three months last sessions intervention postintervention compared results showed intervention group significantly lower levels das compared control group levels das significantly lower intervention group postintervention adding relaxation techniques therapeutic routine costeffective complementary treatment decrease das among ms patients improve qol relevance practice study provides baseline data facilitate investigations future improve quality services delivered patients thus qol satisfactionpmid34691780 pmcpmc8528579 doi101155 2021 8300497,0.0
longitudinal extensive transverse myelitis following chadox1 ncov19 vaccine case report background transverse myelitis tm relatively uncommon condition vaccineassociated myelitis even rarer concern regarding neurological complications following vaccination escalated following report tm safety efficacy trials covid19 vaccinecase presentationwe report first case longitudinal extensive transverse myelitis letm malaysia following administration chimpanzee adenovirusvectored chadox1 ncov19 vaccine 25yearold female presented bilateral lower limb weakness inability walk sensory level t8 absent visual symptoms urgent gadoliniumenhanced magnetic resonance imaging mri spine showed long segment tm thoracic region cerebrospinal fluid autoantibodies antiaquaporin4 antimyelinoligodendrocyte negative diagnosis letm following vaccination made patient started high dose intravenous methylprednisolone patient eventually made recovery following treatmentconclusionletm rare serious adverse reaction following vaccination previously reported cases showed onset symptoms 10 14 days postvaccination suggesting delayed immunogenic reaction however incidence myelitis covid19 much common far greater risk associated vaccination,1.0
objective biomarkers clinical relapse multiple sclerosis metabolomics approach brain commun 2021 oct 12 3 4 fcab240 doi 101093 braincomms fcab240 ecollection 2021abstractaccurate determination relapses multiple sclerosis important diagnosis classification clinical course therapeutic decision making identification biofluid markers multiple sclerosis relapses add current diagnostic armamentarium increase understanding biology underlying clinical expression inflammation multiple sclerosis however presently biofluid marker capable objectively determining multiple sclerosis relapses although particular neurofilamentlight chain shown promise study sought determine metabolic perturbations present multiple sclerosis relapses identify candidate metabolite biomarkers evaluate discriminatory abilities group individual levels comparison neurofilamentlight chain highresolution global targeted 1h nuclear magnetic resonance metabolomics well neurofilamentlight chain measurements performed serum four groups relapsingremitting multiple sclerosis patients stratified time since relapse onset relapse r ii last relapse lr 1 month m 6 m ago iii lr 6 m 24 m ago iv lr 24 m ago two hundred one relapsingremitting multiple sclerosis patients recruited r n 38 lr 16 m n 28 lr 624 m n 34 lr 24 m n 101 using supervised multivariate analysis found global metabolomics profile r patients significantly perturbed compared lr 24 m patients identified discriminatory metabolites quantified using targeted metabolomics lysine asparagine higher r well isoleucine leucine lower r shortlisted potential metabolite biomarkers anova metabolites revealed significant differences across four patient groups clear trend time since relapse onset multivariable receiver operating characteristics analysis four metabolites discriminating r versus lr 24 m showed area curve 0758 area curve serum neurofilamentlight chain 0575 within individual patients paired relapseremission samples four metabolites significantly different relapse versus remission direction change consistent observed group level neurofilamentlight chain discriminatory perturbations identified metabolites point towards energy deficiency immune activation multiple sclerosis relapses measurement metabolites either singly combination useful biomarkers differentiate relapse remission group individual levelspmid34755110 pmcpmc8568847 doi101093 braincomms fcab240,0.0
correlation peripheral cd4+granzb+ctls disease severity patients primary sjgrens syndrome abstractintroductionprimary sjgrens syndrome pss chronic systemic autoimmune disease focal lymphocytic infiltration including majority cd4+ t cells study investigate correlation peripheral granzyme b granzb expressing cd4+ t cells disease severity histological lesion patients pssmethodswe recruited 116 pss 46 health control hc using flow cytometry examine percentage cd4+granzb+ctls peripheral blood immunofluorescence test expression labial glandresultsthe percentage cd4+granzb+ctls significantly upregulated pss hc 71 49 vs 31 19 p 00001 positive correlation essdai frequency markedly higher pss extraglandular manifestations excluding risk factors associated pss still related essdia extraglandular manifestations independently p 005 risk factor extraglandular involvement odds ratio 1928 moreover observed lsgs roc curve analysis indicated area curve auc cd4+granzb+ctls 0796 predict activity pss 0851 presume extraglandular manifestations best diagnostic cutoff point 4865 pss patientsconclusionin study provide new evidence indicating involvement cd4+granzb+ctls activation pathophysiology pss may serve new biomarker evaluate activity severity pss,0.0
transmission amyloidbeta tau pathologies associated cognitive impairments primate abstractamyloid pathology transmission described patients following iatrogenic exposure compounds contaminated proteins can induce cerebral angiopathy resulting brain hemorrhages devastating clinical impacts iatrogenic transmission tau pathology also suspected experimentally proven scenarios lesions detected several decades putatively triggering medicosurgical act however little information regarding cognitive repercussions individuals develop cerebral hemorrhages current study inoculated posterior cingulate cortex underlying corpus callosum young adult primates microcebus murinus either alzheimers disease control brain extracts led widespread tau pathologies alzheimerinoculated animals following 21monthlong incubation period n 12 whereas none control brain extractinoculated animals developed lesions n 6 deposition affected almost cortical regions tau pathology also detected adepositfree regions distant inoculation sites eg entorhinal cortex regions adjacent connected inoculation sites spared eg occipital cortex alzheimerinoculated animals developed cognitive deficits cerebral atrophy compared controls pathologies induced using two different batches alzheimer brain extracts first experimental demonstration tau can transmitted human brain extracts inoculations primate also showed first time transmission widespread tau pathologies can associated cognitive decline results thus reinforce need organize systematic monitoring individuals underwent procedures associated risk tau iatrogenic transmission also provide support alzheimer braininoculated primates relevant models alzheimer pathology,0.0
cm intact ham easily obtained product relevant implications translation regenerative medicine background now well established factors free extracellular vesicles secreted mesenchymal stromal cells msc important mediators msc regenerative actions herein produced secretome conditioned medium cm msc isolated amniotic membrane hamsc cm intact amniotic membrane ham manipulation enzymatic digestion order potentially identify effective easy less expensive secretome produce potential applications regenerative medicine given immunomodulation key mechanism action hamsc contributes tissue regeneration used comprehensive panel vitro immunomodulatory tests compare cmsmethodsamniotic membranes either cut fragments used hamsc isolation cms hamsc passages 0 2 collected standard 5day culture cm ham collected 2 5day culture immunomodulation assessed terms pbmc tcell proliferation tcell subset polarization tregulatory cell induction cell cytotoxicity monocyte differentiation toward antigenpresenting cells furthermore performed comparison cm obtained single donors pooled cm also assessed impact lyophilization immunomodulatory properties cmresultswe demonstrate cm ham comparable immunomodulatory properties cm hamsc passages 0 2 furthermore demonstrate pooled cms similar effects compared cm single donors used separately finally demonstrate lyophilization alter vitro immunomodulatory properties cm ham hamscconclusionsthe results presented herein support possibility produce secretome intact ham open prospect highly improve scalability gmp production process reducing costs time related process cell isolation expansion moreover possibility lyophilized secretome maintains original properties allow readytouse product easier handling shipping storage use lyophilized product will also facilitate clinicians permitting customized reconstitution volumes methods according suitable formula required clinical application,0.0
mast cells important regulators autoimmunity cancer development front cell dev biol 2021 oct 12 9752350 doi 103389 fcell2021752350 ecollection 2021abstractmast cells essential part immune system best known important modulators allergic anaphylactic immune responses upon activation mast cells release multitude inflammatory mediators various effector functions can protective damageinducing mast cells can antiinflammatory proinflammatory immunological effect play important roles regulating autoimmune diseases including rheumatoid arthritis type 1 diabetes multiple sclerosis importantly chronic inflammation autoimmunity linked development specific cancers including pancreatic cancer prostate cancer colorectal cancer gastric cancer inflammatory mediators released activated mast cells regulate immune responses promote vascular permeability recruitment immune cells site inflammation mast cells present increased numbers tissues affected autoimmune diseases well tumor microenvironments colocalize t regulatory cells t effector cells mast cells can regulate immune responses expressing immune checkpoint molecules surface releasing antiinflammatory cytokines promoting vascularization solid tumor sites result immune modulating activities mast cells diseasemodifying roles specific autoimmune diseases cancers therefore determining regulate activities mast cells different inflammatory tumor microenvironments may critical discovering potential therapeutic targets treat autoimmune diseases cancerpmid34712668 pmcpmc8546116 doi103389 fcell2021752350,0.0
ancestral diversity limited published t cell receptor sequencing studies immunity 2021 oct 12 54 10 21772179 doi 101016 jimmuni202109015no abstractpmid34644550 doi101016 jimmuni202109015,0.0
sarcopenia index based serum creatinine cystatin c predicts risk postoperative complications following hip fracture surgery older adults abstractobjectiveto assess utility preoperative sarcopenia index si predictive marker risk postoperative complications following hip fracture surgery older adultsstudy designthis observational study enrolled older adults hip fracture hospitalized department orthopedics west china hospital sichuan university december 7 2010 june 14 2017 underwent hip fracture surgeryprimary outcome measuresclinical data collected medical records serum creatinine cystatin c measured surgery outcomes included postoperative complications pneumonia urinary tract infection respiratory failure heart failure nongrade healing binary logistic regression analyses used analyze association si postoperative complicationsresultsa total 897 patients aged 60 years enrolled study age range 60 100 years 306 341 male 591 659 female postoperative complications included pneumonia 12 urinary tract infections 18 respiratory failure 15 heart failure 16 nona grade healing 36 patient group received joint replacements incidence pneumonia negatively associated si values adjusting potential confounding factors binary logistic regression analyses showed higher si independently associated lower risk pneumonia joint replacement surgery or039 95 ci018089 p005 however find statistically significant association si risk postoperative complications pneumonia among patients two types hip fracture surgeryconclusionthe si based serum creatinine cystatin c can predict pneumonia rather postoperative complications among older patients hip fracture joint replacement surgery,0.0
linking microstructural integrity motor cortex excitability multiple sclerosis front immunol 2021 oct 12 12748357 doi 103389 fimmu2021748357 ecollection 2021abstractmotor skills frequently impaired multiple sclerosis ms patients following grey white matter damage cortical excitability abnormalities applied advanced diffusion imaging 3t magnetic resonance tomography neurite orientation dispersion density imaging noddi well diffusion tensor imaging dti 50 ms patients 49 agematched healthy controls quantify microstructural integrity motor system assess excitability determined resting motor thresholds using noninvasive transcranial magnetic stimulation measures cognitivemotor performance conducted neuropsychological assessments including ninehole peg test trail making test part b tmta tmtb symbol digit modalities test sdmt patients evaluated clinically including assessments expanded disability status scale hierarchical regression model revealed lower neurite density index ndi primary motor cortex suggestive axonal loss grey matter predicted higher motor thresholds ie reduced excitability ms patients p 009 adjusted r 0117 furthermore lower ndi indicative decreased cognitivemotor performance p 007 adjusted r 142 tmta p 009 adjusted r 129 tmtb p 006 adjusted r 142 sdmt motor wm tracts patients characterized overlapping clusters lowered ndi p 05 cohens d 0367 dtibased fractional anisotropy fa p 05 cohens d 0300 ndi exclusively detecting higher amount abnormally appearing voxels orientation dispersion index motor tracts increased patients compared controls suggesting decreased fiber coherence p 05 cohens d 0232 study establishes link microstructural characteristics excitability neural tissue well cognitivemotor performance multiple sclerosis demonstrate noddi parameters neurite density index orientation dispersion index detect larger amount abnormally appearing voxels patients compared healthy controls opposed classical dti parameter fa work outlines potential microstructure imaging using advanced biophysical models forecast excitability alterations neuroinflammationpmid34712236 pmcpmc8546169 doi103389 fimmu2021748357,0.0
impact demographic clinical characteristics trajectories healthrelated quality life among patients fabry disease background fabry disease fd xlinked lysosomal storage disorder characterized multiorgan dysfunction since individuals fd usually experience progressive clinical disease manifestations healthrelated quality life hrqol expected change time however limited longitudinal research examining hrqol outcomes individuals fd aimed assess longitudinal outcomes hrqol adults fd examine physical mental hrqol trajectories initial registration baseline 35 year 713 year followups evaluate possible associations age sex medical complications physical mental hrqol trajectoriesmethodsfortythree individuals fd 53 female aged 18 81 years baseline attended clinical followup visits 2006 2020 medical records extracted retrospectively demographics 36item shortform health survey sf36 recorded scheduled visits except last data collection prospectively obtained 2020 physical pcs mental mcs composite scores sf36 chosen outcome measuresresultsthe eight sf36 domain scores stable span 13 years physical social functioning domains worsened clinically followup period mean baseline sf36 domain scores significantly lower decreased hrqol fd sample compared norwegian population norms two hierarchical linear models run examine whether demographics medical complications measured last clinical visit predicted physical mental hrqol trajectories age 47 years p 0001 male sex p 0027 small fibre neuropathy p 0001 renal dysfunction p 0001 cerebrovascular events p 0003 associated lower hrqol time significant interactions found time follow abovementioned predictors hrqolconclusionsoverall hrqol trajectories remained stable baseline 35 year 713 year followups majority individuals reporting decreased physical mental hrqol medical complications combination older age male sex important predictors lower hrqol fd awareness relationship valuable health care providers patients findings provide indicators can guide treatment decisions improve physical mental hrqol outcomes,0.0
predictors mortality among patients type 2 diabetes jordan background diabetes mellitus dm common metabolic disease associated increased risk mortalityobjectivethe aim study examine predictors mortality among patients type 2 diabetes north jordanmethodselectronic data files diabetes patients admitted period 20142018 tertiary center north jordan reviewed patients characteristics clinical laboratory data use medications mortality rate collectedresultsmean age patients n 957 6099 037 mean sem patients multiple risk factors underlying cardiovascular diseases cvds mortality rate 101 univariate predictors mortality included age chronic kidney disease ckd acute kidney injury hypertension heart failure hf coronary artery disease venous thromboembolism vte stroke atrial fibrillation af chronic obstructive pulmonary disease copd number cvds increases mortality rate also increases odd ratio 20 p 00001 use insulin aspirin acei arbs beta blockers diuretics also associated mortality fasting glucose percentage glycated hemoglobin associated mortality multivariable logistic regression analysis adjusting confounders collinearity age hf af copd vte ckd associated mortalityconclusionkey risk factors mortality cvds ckd indicating primary step management focus optimizing risk factors prevent diabetes complications death,0.0
current knowledge challenges associated targeted delivery neurotrophic factors central nervous system focus available approaches abstractduring last decades numerous basic clinical studies conducted assess delivery efficiency therapeutic agents brain spinal cord parenchyma using several administration routes among conventional inprogress administrative routes eligibility stem cells viral vectors biomaterial systems shown delivery ntfs despite manifold advances close association delivery system regeneration outcome remains unclear herein aimed discuss recent progress delivery factors pros cons related modality,0.0
teriflunomide promotes oligodendroglial 8 9unsaturated sterol accumulation cns remyelination neurol neuroimmunol neuroinflamm 2021 oct 12 8 6 e1091 doi 101212 nxi0000000000001091 print 2021 novabstractbackground objectives test whether low concentrations teriflunomide tf promote remyelination investigate effect tf oligodendrocyte culture remyelination vivo 2 demyelinating modelsmethods effect tf oligodendrocyte precursor cell opc proliferation differentiation assessed vitro glial cultures derived neonatal mice confirmed fluorescenceactivated cell sortingsorted adult opcs levels 8 9unsaturated sterols lanosterol zymosterol quantified tf shamtreated cultures vivo tf administered orally remyelination assessed myelin basic proteingfpnitroreductase mbpgfpntr transgenic xenopus laevis demyelinated metronidazole adult mice demyelinated lysolecithinresults cultures low concentrations tf 10 nm decreased opc proliferation increased differentiation effect also detected adult opcs oligodendrocyte differentiation induced tf abrogated oxidosqualene cyclase inhibitor ro 488071 mediated accumulation zymosterol demyelinated tadpole tf enhanced regeneration mature oligodendrocytes 25fold mouse demyelinated spinal cord tf promoted differentiation newly generated oligodendrocytes factor 17fold significantly increased remyelinationdiscussion tf enhances zymosterol accumulation oligodendrocytes cns myelin repair beneficial offtarget effect investigated patients multiple sclerosispmid34642237 doi101212 nxi0000000000001091,1.0
retinal oxygen metabolism haemodynamics patients multiple sclerosis history optic neuritis front neurosci 2021 oct 12 15761654 doi 103389 fnins2021761654 ecollection 2021abstractvascular changes alterations oxygen metabolism suggested implicated multiple sclerosis ms pathogenesis progression recently developed vivo retinal fundus imaging technologies provide now opportunity noninvasively assess metabolic changes neural retina study performed assess retinal oxygen metabolism peripapillary capillary density cd large vessel density lvd retinal nerve fiber layer thickness rnflt ganglion cell inner plexiform layer thickness gciplt patients diagnosed relapsing multiple sclerosis rms history unilateral optic neuritis 16 rms patients 18 healthy controls hc included study retinal oxygen extraction modeled using o2 saturations doppler optical coherence tomography doct derived retinal blood flow rbf data cd lvd assessed using optical coherence tomography oct angiography rnflt gciplt measured using structural oct measurements performed eyes ms+on without mson history rms patients one eye hc total oxygen extraction lowest ms+on 18 02 l o2 min higher mson 21 05 l o2 min p 0019 vs ms+on highest hc eyes 23 06 l o2 min p 0002 vs ms anova p 0031 rbf lower ms+on 332 60 l min compared mson 383 46 l min p 0005 vs ms+on hc eyes 372 47 l min p 0014 vs ms+on anova p 0010 cd lvd rnflt gcipl significantly lower ms+on eyes present data suggest structural alterations retina rms patients accompanied changes oxygen metabolism pronounced ms+on mson eyes whether alterations promote ms onset progression occur consequence disease warrants investigation clinical trial registration clinicaltrialsgov registry nct03401879pmid34712117 pmcpmc8546107 doi103389 fnins2021761654,0.0
new relapse multiple sclerosis neuromyelitis optica potential adverse event astrazeneca azd1222 vaccination covid19 abstractwe report nine patients eight cases ms one case nmosd presented disease relapse close temporal association first azd1222 vaccination dose covid19 patients stable median period six years evidence disease activity change medication median 13 days 7 25 days vaccination developed new relapse increased disability new lesions magnetic resonance imaging although exceedingly rare might adverse event azd1222,0.0
molecular biology autoinflammatory diseases abstractthe long battle humans various physical chemical biological insults cause cell injury eg products tissue damage metabolites infections led evolution various adaptive responses responses triggered recognition damageassociated molecular patterns damps pathogenassociated molecular patterns pamps usually cells innate immune system damps pamps recognized pattern recognition receptors prrs expressed innate immune cells recognition triggers inflammation autoinflammatory diseases strongly associated dysregulation prr interactomes include inflammasomes nfbactivating signalosomes type interferoninducing signalosomes immunoproteasome disruptions regulation interactomes leads inflammasomopathies relopathies interferonopathies proteasomeassociated autoinflammatory syndromes respectively review discuss currently accepted molecular mechanisms underlying several autoinflammatory diseases,0.0
mesenchymal stem#x2f stromal cell therapy atopic dermatitis chronic urticaria immunological clinical viewpoints abstractallergic diseases immunemediated diseases allergies share common immunopathogenesis specific differences according specific disease mesenchymal stem stromal cells mscs applied people suffering allergic many diseases review immunologic roles mscs systemically reviewed according disease immunopathogenesis clinical viewpoint mscs seem promising therapeutic modality symptomatic treatments also causative even preventive treatments allergic diseases including atopic dermatitis chronic urticaria,0.0
impact body mass index age relapsingremitting multiple sclerosis onset retrospective study neurol int 2021 oct 11 13 4 517526 doi 103390 neurolint13040051abstracta backround multiple sclerosis ms complex chronic disease central nervous system cns body mass index bmi component metabolic syndrome mets considered among risk factors ms however role ms remains ambiguousobjective examine impact bmi age onset patients relapsingremitting ms rrms greek cohortmethods data 821 greek patients rrms collected bmi values considered quartiles comparisons demographic characteristics quartiles made pearsons chisquare test categorical variables anova continuous variables overall pvalue calculated corresponding trend association case significant association posthoc analysis performed order identify differences demographic characteristics specific bmi quartiles groups linear regression analyses used assess relationship bmi age onset msresults comparisons participant characteristics quartiles bmi revealed participants highest bmi older age disease onset results linear regression analysis showed increase 1 bmi unit age rrms onset increases 0255 95 ci 0136 0374 years p 0001conclusions patients higher bmi parameter mets exhibit increased age rrms onset results may present alternative personalized approach diagnosis prognosis prevention rrmspmid34698268 doi103390 neurolint13040051,0.0
neuronal nmnat2 overexpression achieve significant neuroprotection experimental autoimmune encephalomyelitis#x2f optic neuritis front cell neurosci 2021 oct 11 15754651 doi 103389 fncel2021754651 ecollection 2021abstractoptic neuritis inflammation demyelination optic nerve one common clinical manifestations multiple sclerosis affected patients suffer persistent visual symptoms due degeneration secondary retinal ganglion cell rgc death mouse experimental autoimmune encephalomyelitis eae model replicates optic neuritis significant rgc soma axon loss nicotinamide mononucleotide adenylyltransferases nmnats nad+synthetic enzymes shown essential axon integrity activation significantly delays axonal wallerian degeneration nmnat2 enriched axons proposed promising therapeutic target axon injuryinduced neurodegeneration therefore investigated whether activation nmnat2 can used gene therapy strategy neuroprotection eae optic neuritis avoid confounding effects inflammatory cells play important roles eae initiation progression used rgcspecific promoter drive expression long halflife nmnat2 mutant mouse rgcs vivo however optical coherence tomography vivo retina imaging reveal significant protection ganglion cell complex visual function assays pattern electroretinography optokinetic response also showed improvement mice nmnat2 overexpression postmortem histological analysis retina wholemounts semithin sections confirmed vivo results nmnat2 activation rgcs provide significant neuroprotection rgcs eae optic neuritis studies suggest different degenerative mechanism wallerian degeneration involved autoimmune inflammatory axonopathy nmnat2 may major contributor mechanismpmid34707482 pmcpmc8542903 doi103389 fncel2021754651,1.0
p38 map kinase signaling microglia plays sexspecific protective role cns autoimmunity regulates microglial transcriptional states front immunol 2021 oct 11 12715311 doi 103389 fimmu2021715311 ecollection 2021abstractmultiple sclerosis ms autoimmune demyelinating disease central nervous system representing leading cause nontraumatic neurologic disease young adults disease three times common women yet severe men mechanisms underlying sex differences remain largely unknown ms initiated autoreactive t helper cells cnsresident cnsinfiltrating myeloid cells key proximal effector cells regulating disease pathology previously shown genetic ablation p38 map kinase broadly myeloid lineage protective autoimmune model ms experimental autoimmune encephalomyelitis eae females males precisely define mechanisms responsible used multiple genetic approaches bone marrow chimeras ablate p38 microglial cells peripheral myeloid cells deletion p38 cell types recapitulated previous sex difference reduced eae severity females unexpectedly deletion p38 periphery protective sexes contrast deletion p38 microglia exacerbated eae males revealing opposing roles p38 microglia vs periphery bulk transcriptional profiling revealed p38 regulated expression distinct gene modules male vs female microglia singlecell transcriptional analysis wt p38deficient microglia isolated inflamed cns revealed diversity complex microglial states connected distinct convergent transcriptional trajectories males microglial p38 deficiency resulted enhanced transition homeostatic diseaseassociated microglial states downregulation regulatory genes atf3 rgs1 socs3 btg2 increased expression inflammatory genes cd74 trem2 mhc class ii genes females effect p38 deficiency divergent exhibiting unique transcriptional profile included upregulation tissue protective genes small subset inflammatory genes also upregulated males taken together results reveal p38dependent sexspecific molecular pathway microglia protective cns autoimmunity males suggesting autoimmunity males females driven distinct cellular molecular pathways thus suggesting design future sexspecific therapeutic approachespmid34707603 pmcpmc8542909 doi103389 fimmu2021715311,1.0
society cardiovascular magnetic resonance 2020 case week series abstractthe society cardiovascular magnetic resonance scmr international society focused research education clinical application cardiovascular magnetic resonance cmr case week case series hosted scmr website https wwwscmrorg demonstrates utility importance cmr clinical diagnosis management cardiovascular disease case consists clinical presentation discussion condition role cmr diagnosis guiding clinical management cases instructive helpful approach patient management present digital archive 2020 case week series 11 cases means enhancing education interested cmr means readily identifying cases using pubmed similar search engine,0.0
sociodemographic clinical factors associated depression anxiety general mental health people multiple sclerosis covid19 pandemic abstractbackground people multiple sclerosis pwms may increased risk psychological distress covid19 study selfreported mental health us pwms covid19 prior vaccine rolloutmethods crosssectional survey distributed online pwms iconquerms 12 18 202002 10 2021 depressive anxiety symptom burdens general mental health status measured via patienthealth questionnaire9 generalized anxiety disorder7 promis global mental health scales linear regression models assessed associations mental health variables age sex disability status comorbidities social determinants healthresults 610 us pwms mean age 56 years standard deviation 11 range 2085 female 81 relapsing remitting disease 62 previous depression diagnosis 40 prevalences moderatetosevere depressive anxiety symptom burden 274 147 respectively 551 endorsed fair poor general mental health pwms tested positive covid19 n47 77 reported higher depressive anxiety symptom burdens p05 increased disability status score social determinants health associated depressive symptoms worse general mental health younger age associated increased depressive anxiety symptom burdens worse general mental health female sex associated greater anxiety symptomsconclusion specific associations worse mental health among pwms covid19 reflect combination clinical demographic social determinants health multidisciplinary care teams vigilance important address ongoing mental health impacts covid19 pwms,0.0
appraisal antigen identification igg effector functions driving host immune responses multiple sclerosis abstractincreased immunoglobulin g igg antibodies oligoclonal bands ocb characteristic features multiple sclerosis ms neuroinflammatory demyelinating disease neurodegeneration chronic stages ocb shown associated disease activity brain atrophy despite intensive research last several decades antigen specificities igg ms remained elusive present evidence supports intrathecal igg driven antigenstimulation therefore provide reasoning failed ms antigen identification presence codeposition igg activated complement products ms lesions suggest igg effector functions may play critical role disease pathogenesis,1.0
genetic impact ebola outbreak wild gorilla population background numerous ebola virus outbreaks occurred equatorial africa past decades besides human fatalities gorillas chimpanzees also succumbed fatal virus 2004 outbreak odzalakokoua national park republic congo alone caused severe decline resident western lowland gorilla gorilla gorilla gorilla population 95 mortality rate explore immediate genetic impact ebola outbreak western lowland gorilla populationresultsassociations survivorship evaluated utilizing dna obtained fecal samples 16 gorilla individuals declared missing outbreak nonsurvivors 15 individuals observed epidemic survivors used target enrichment approach capture sequences 123 genes previously associated immunology ebola virus resistance additionally analyzed gut microbiome influence survival infection results indicate changes population genetic diversity ebola outbreak significant differences microbial community composition survivors nonsurvivors however despite low power association analysis detect six nominally significant missense mutations four genes might candidate variants associated increased chance survivalconclusionthis study offers first insight genetics wild great ape population ebola outbreak using target capture experiments fecal samples presents list candidate loci may facilitated survival,0.0
microbiotagutbrain axis epilepsy review mechanisms potential therapeutics front immunol 2021 oct 11 12742449 doi 103389 fimmu2021742449 ecollection 2021abstractthe gutbrain axis refers bidirectional communication gut brain regulates intestinal homeostasis central nervous system via neural networks neuroendocrine immune inflammatory pathways development sequencing technology evidenced key regulatory role gut microbiota several neurological disorders including parkinsons disease alzheimers disease multiple sclerosis epilepsy complex disease multiple risk factors affect 50 million people worldwide nearly 30 patients epilepsy controlled drugs interestingly patients inflammatory bowel disease susceptible epilepsy ketogenic diet effective treatment patients intractable epilepsy based clinical facts role microbiome gutbrain axis epilepsy ignored review discuss relationship gut microbiota epilepsy summarize possible pathogenic mechanisms epilepsy perspective microbiota gutbrain axis discuss novel therapies targeting gut microbiota better understanding role microbiota gutbrain axis especially intestinal one help investigate mechanism diagnosis prognosis evaluation treatment intractable epilepsypmid34707612 pmcpmc8542678 doi103389 fimmu2021742449,0.0
emerging roles dysregulated adenosine homeostasis brain disorders specific focus neurodegenerative diseases abstractin modern societies increase older population agerelated neurodegenerative diseases progressively become greater socioeconomic burdens date despite tremendous effort devoted understanding neurodegenerative diseases recent decades treatment delay disease progression largely ineffective urgent demand development new strategies targeting pathological features timely topic important note degenerative diseases associated accumulation specific misfolded proteins facilitated several common features neurodegenerative diseases including poor energy homeostasis mitochondrial dysfunction adenosine purine nucleoside neuromodulator brain also essential component energy production pathways cellular metabolism gene regulation brain cells levels intracellular extracellular adenosine thus tightly controlled handful proteins including adenosine metabolic enzymes transporters maintain proper adenosine homeostasis notably disruption adenosine homeostasis brain various pathophysiological conditions documented past two decades adenosine receptors particularly a1 a2a adenosine receptors actively investigated important drug targets major degenerative diseases unfortunately except a2a antagonist istradefylline administered adjuvant treatment levodopa parkinsons disease effective drug based adenosine receptors developed neurodegenerative diseases review summarize emerging findings proteins involved control adenosine homeostasis brain discuss challenges future prospects development new therapeutic treatments neurodegenerative diseases associated disorders based understanding adenosine homeostasis,0.0
factors associated mortality rheumatoid arthritisassociated interstitial lung disease systematic review metaanalysis background interstitial lung disease ild common potentially lifethreatening complication rheumatoid arthritis ra patients however lack clear prognostic factors rheumatoid arthritisassociated interstitial lung disease raild patients purpose study complete systematic review metaanalysis factors associated mortality raild patientsmethodsmedline embase cochrane library searched september 1 2020 newcastleottawa scale nos applied assess methodological quality eligible studies study characteristics magnitude effect sizes extracted pooled hazard ratios hrs corresponding 95 confidence intervals cis pooled risk ratios rrs 95 cis calculated assess factors associated mortality raildresultstwentythree 3463 articles eligible ten factors associated mortality raild evaluated metaanalysis older age hrs 104 95 ci 103105 male sex hrs 144 95 ci 121173 smoking history hrs 142 95 ci 103196 lower diffusing capacity lung carbon monoxide dlco predicted hrs 098 95 ci 097100 forced vital capacity fvc predicted hrs 099 95 ci 098100 composite physiological index cpi hrs 104 95 ci 102106 usual interstitial pneumonia uip pattern hrct hrs 188 95 ci 114310 rrs 190 95 ci 150239 emphysema presence hrs 231 95 ci 158339 acute exacerbation ild hrs 270 95 ci 167436 associated increased mortality raild whereas rheumatoid factor rf positive status associatedconclusionsthrough systematic review metaanalysis found older age male sex smoking history higher cpi lower dlco predicted lower fvc predicted uip pattern hrct emphysema presence acute exacerbation ild associated increased risk mortality raild,0.0
bisperoxovanadium promotes motor neuron survival neuromuscular innervation amyotrophic lateral sclerosis abstractamyotrophic lateral sclerosis als common motor neuron mn disease present cure progressive loss mns hallmark als previously shown therapeutic effects phosphatase tensin homolog pten inhibitor potassium bisperoxo picolinato vanadium bpv pic models neurological injury demonstrated significant neuroprotective effects mn survival however accumulating evidence suggests pten detrimental mn survival als therefore hypothesized treating mutant superoxide dismutase 1 g93a msod1g93a mouse model als motor neuron degeneration vitro model msod1g93a motor neuron injury bpv pic prevent motor neuron loss test hypothesis treated msod1g93a mice intraperitoneally daily 400 g kg bpv pic 70 90 days age immunolabeled mns microglial reactivity analyzed lumbar spinal cord tissue bpv pic treatment significantly ameliorated ventral horn motor neuron loss msod1g93a mice p 0003 significantly altering microglial reactivity p 0701 treatment bpv pic also significantly increased neuromuscular innervation p 0018 affect muscle atrophy also cultured motor neuronlike nsc34 cells transfected plasmid overexpress mutant sod1g93a starved serumfree medium 24 h without bpv pic downstream inhibitor akt signaling ly294002 vitro bpv pic improved neuronal viability akt inhibition reversed protective effect p 005 conclusion study indicates systemic bpv pic treatment valuable neuroprotective therapy als,1.0
age differences trajectories selfrated health young people multiple sclerosis backgroundrecent evidence suggested existence multiple sclerosis ms prodrome hence young adults ms likely symptoms childhood adolescence therefore reasonable assume people aged 25 years ms might pediatriconset contrast young people aged 26 35 less likely pediatriconset contrasting two groups people lead valuable information impact ms time purpose study characterize selfrated health srh young people ms changed time estimate extent srh differs age groups 18 25 years 26 35 years sexmethodsthis study utilized placebo arm data multiple sclerosis outcome assessment consortium database responses rand36 srh item 393 participants included groupbased trajectory models gbtm used identify patterns change two years ordinal regression performed estimate whether trajectory groups differed age group sex relapse eventresultsresults gbtm showed groups stable time except one progressing rating good excellent posterior probabilities showed 35 people consistently rated health good excellent 2 consistently rated health poor health perceptions differed across age groups 05 17 ci 11 26 sex 01 09 ci 06 13 compared younger group people aged 26 35 years 17 times likely rate health poorer people relapses also 22 times likely rate health poorer 08 22 ci 15 32 conclusiontrajectories srh young people ms relatively stable absence drug treatment people younger group 25 years rated health better slightly older group consistent lower disability,0.0
paraneoplastic encephalomyeloradiculits multiple autoantibodies itpr1 gfap mog case report literature review background recently antibodies alpha isoform glialfibrillaryacidicprotein gfap identified small series patients encephalomyelitis coexisting autoantibodies nmda receptor gad65 antibodies described patients describe patient rapidly progressive encephalomyeloradiculitis combination antiitpr1 antigfap antimog antibodiescase presentation literature reviewa 44year old caucasian woman flulike prodrome presented meningism progressive cerebellar signs autonomic symptoms areflexia quadriplegia respiratory insufficiency mri showed diffuse bilateral t2whyperintense brain lesions cortex white matter corpus callosum well longitudinal lesion medulla oblongata entire spinal cord antiitpr1 antigfap antimog antibodies detected cerebrospinal fluid along lymphocytic pleocytosis borderline tumor ovary diagnosed thus disease patient deemed paraneoplastic patient treated surgical removal tumor steroids immunoglobulins plasma exchange rituximab four months presentation patient still tetraplegic reacted mimic expressions pain touch phonate solitary vowels extensive literature research performedconclusionour case literature review illustrate multiple glial neuronal autoantibodies can cooccur points paraneoplastic etiology ovarian teratoma thymoma clinical manifestation can mixture typically associated syndromes eg ataxia associated antiitpr1 antibodies encephalomyelitis antigfap antibodies longitudinal extensive myelitis antimog antibodies,0.0
cyclophosphamide highly aggressive marburglike multiple sclerosis ther adv neurol disord 2021 oct 10 1417562864211050028 doi 101177 17562864211050028 ecollection 2021no abstractpmid34659455 pmcpmc8512236 doi101177 17562864211050028,0.0
engaging people longterm health conditions communitybased physical activity initiative qualitative followup study evaluating parkrun prove project background parkrun running volunteering everyone prove project example communitybased physical activity volunteering initiative people living longterm health conditions england 3 year project involved appointing volunteer outreach ambassadors whose role promote parkrun people living longterm health conditions various outreach activities qualitative study aimed understand experience delivering project perspective volunteer outreach ambassadors prove project managermethodsthe prove project manager ten prove outreach ambassadors across nine health condition groups interviewed researcher asthma blood pressure deaf hard hearing dementia diabetes endometriosis heart conditions learning disabilities autism obesity interview transcripts analysed using thematic analysisresultsfour themes nine subthemes generated participants highlighted challenges measuring projects success bringing meaningful lasting change reflected value project learning opportunity despite successes thought project limited reach outside existing parkrun community outreach ambassadors reflected experiences role skills required finding rewarding highlighting importance networking forming connections key stakeholders findings discussed comparison interviews conducted outreach ambassadors 12 months earlierconclusionsthis study provides evidence support public health potential parkrun though targeted initiatives prove project provides critical reflection worked work delivering project findings relevance organisations wishing implement similar outreach initiatives using volunteer workforce including recommendations resource management communication leadership fostering volunteer autonomy defining capturing success,0.0
musc19 study egyptian cohort abstractobjective study aimed report severity covid19 cohort egyptian patients multiple sclerosis ms particular attention impact disease modifying drugs dmds methods study population included 119 ms patients recruited two centers ainshams university cairo university confirmed suspected covid19 period may september 2020 part musc19 project univariate logistic regression fitted assess risk factors severe covid19 least one outcome among hospitalization icu admission death results females 77 mean age 34 years mean duration ms 528 years median edss 3 patients 83 rrms 13 2 respectively spms ppms eleven patients 9 study population severe outcome 3 patients 3 died headache symptom significantly associated severity covid19 or1085 p0001 association dmds severe covid19 outcomeconclusion study showed acceptable safety profile dmds egyptian ms patients developed covid19 91 cohort favorable outcome headache symptom associated severe outcome egyptian patientsnull needs validation,0.0
multiple sclerosis phenotype germany abstractbackground diagnosis multiple sclerosis ms can categorized based disease course following phenotypes relapsingremitting ms rrms primary progressive ms ppms secondary progressive ms spms one exception studies ms phenotype either provide prevalence data describing drug utilization emphasis patients rrms drug utilization phenotype tends examined course year recent studies comprehensively evaluated ms phenotypes prevalence drug utilization comorbidities time populationbased perspective essential understanding disease burden identifying unmet needs ms germany one countries specific ms phenotypes commonly recorded routine clinical practice purpose study compare ms phenotypes respect changes populationbased prevalence rates types ms treatments prescribed time well frequency clinical conditions associated ms based data german health insurance databasemethods retrospective observational cohort study used data german health insurance database period 2010 2017 patients aged 18+ years specified phenotype ms based icd10 diagnosis coding included analysisresults 2010 rrms reported 73 ppms 8 spms 19 patients ms known phenotype mean ages patients 414 536 528 years respectively phenotypes associated female predominance 69 63 63 respectively prevalence rate phenotype markedly increased study period rrms +113 ppms +40 spms +54 2017 rates 183 14 34 per 100 000 respectively mean age patients reporting phenotype also increased p001 femalemale proportion remained stable rrms spms proportion females significantly declined time ppms group overall percentage patients prescribed diseasemodifying drug increased across phenotypes 51 57 prescription interferonbased therapies declined phenotype greatest declines observed rrms ppms ppms spms groups significantly prescriptions symptom management rrms group depression prevalent clinical condition associated phenotype significant difference percentage patients depression across phenotypes p003 highest among spms 44 compared rrms 35 ppms 37 significant differences p005 across phenotypes also observed composite prevalence cardiovascular conditions highest ppms cognitive dysfunction highest spms conclusion increasing numbers patients across ms phenotype aging population patients ms regardless phenotype gender differences variations across types treatments prescribed clinical conditions associated ms phenotype present new insight disease burden treatment strategies ms considered developing healthcare strategies optimizing care patients ms,0.0
acute fibrinous organizing pfneumonia two case reports literature review background acute fibrinous organizing pneumonia afop rare histologic interstitial pneumonia pattern characterized intraalveolar fibrin deposition organizing pneumonia clinical characteristics still well known consensus treatment yetcase presentationwe report two female cases fifties diagnosed afop confirmed second lung biopsy case 1 idiopathic afop manifestation 6week fever dyspnea cough case 2 secondary systemic lupus erythematosus fever major symptom chest ct scans revealed bilateral multiple consolidations predominantly lower lobes cases initially diagnosed pneumonia improve treatment broadspectrum antibiotics cases transbronchial biopsy bronchoalveolar lavage fluid examination inconclusive pathological diagnosis confirmed percutaneous lung biopsy patients good clinical response prednisoneconclusionswe report two rare afop cases highlight importance awareness disease perform comprehensive review date afop including 150 patients since 2002 consolidation common imaging pattern followed groundglass opacity nodules lung biopsy required definitive diagnosis corticosteroids recommended effective therapy treatment options depend etiology disease severity,0.0
application definitions conversion secondary progressive ms danish nationwide population abstractbackgroundthe number patients relapsing remitting multiple sclerosis rrms convert secondary progressive sp ms uncertain emerging treatment options spms important identify rrms patients transition sp phase objective present study characterize clinical parameters use disease modifying therapies patients diagnosed spms rrms patients already entered sp phase use danish multiple sclerosis registry dmsr methodswe used crosssectional design including living patients ms june 30 2020 dmsr first applied msbase definition spms rrms patients second applied slightly modified inclusion criteria expand clinical trial patients clinically confirmed spms patients rrms fulfilling msbase definition spms identify spms patients recently progressed may benefit treatment disease modifying therapy compared clinical characteristics diseasemodifying therapy use different patient groupsresultsamong patients clinically confirmed spms application slightly modified expand trial inclusion criteria spms mexpand captured patients converted spms recently relapsed initiated highefficacy treatment frequently moreover rrms patients fulfilling spmscriteria according msbase recently progression according mexpand similar characteristics remarkably resembled spms population expand trialconclusionour results indicate datadriven diagnostic definitions might help identify rrms patients risk spms highlight challenges reluctance diagnosing spms clinical practice,0.0
social cognitive theory variables correlates physical activity fatigued persons multiple sclerosis abstractbackground interest application behavioral interventions based theory increasing physical activity among adults multiple sclerosis ms date researchers applied theory social cognitive theory sct identifying correlates physical activity can inform design delivery behavioral interventions research often conducted heterogeneous samples persons ms without focus specific symptom fatigue may targeted physical activity behavioral interventions end study examined sct variables ie selfefficacy barriers outcome expectations goalsetting planning social support functional limitations correlates physical activity persons ms selfreported elevated fatiguemethods persons ms n210 aged 496 132 years ambulated without assistance participated study participants completed selfreport measures fatigue physical activity sct variables wore actigraph gt3x+ accelerometer belt around waist 7 days accelerometer data processed delineated time spent light moderatetovigorous physical activity mvpa based msspecific cutpoints generated groups fatigued n134 nonfatigued n76 persons ms based cutoff score 4 fatigue severity scaleresults differences physical activity sct variables fatigued nonfatigued persons ms among fatigue functional limitations 052 selfefficacy 031 goalsetting 025 associated devicemeasured mvpa sct variables except outcome expectations associated selfreported physical activity regression analyses indicated selfefficacy functional limitations goalsetting significant correlates mvpa fatigueconclusion selfefficacy goalsetting social support barriers may important targets sctbased behavioral interventions increasing physical activity among persons ms fatigue,0.0
relapseindependent multiple sclerosis progression natalizumab brain commun 2021 oct 9 3 4 fcab229 doi 101093 braincomms fcab229 ecollection 2021abstractthe objective study investigate confirmed progression independent relapse activity relapsingremitting multiple sclerosis patients longterm natalizumab treatment performed retrospective crosssectional study clinical data captured 1994 2019 two german multiple sclerosis tertiary referral centres data files relapsingremitting multiple sclerosis patients treated natalizumab 24 months analysed confirmed progression independent relapse activity defined 12 week confirmed disability progression roving expanded disability status scale reference score 1 point patients expanded disability status scale score 3 05 patients expanded disability status scale score 35 absence relapse cox proportional hazard models used analyse probability developing confirmed progression independent relapse activity depending disease natalizumab treatment duration among 184 patients identified 44 24 developed confirmed progression independent relapse activity natalizumab irrespective expanded disability status scale score natalizumab onset time confirmed progression independent relapse activity affected expanded disability status scale natalizumab onset categorized expanded disability status scale score 35 versus 35 duration disease duration therapy confirmed progression independent relapse activity occurred earlier disease course patients earlier natalizumab therapy onset regard disease duration stepwise forward regression analysis revealed disease duration main factor confirmed progression independent relapse activity development p 0005 taken together confirmed progression independent relapse activity occurs substantial proportion patients longterm natalizumab treatment independent expanded disability status scale score natalizumab onset findings suggest patients initiated natalizumab early disease course usually order treat aggressive clinical phenotype higher risk early confirmed progression independent relapse activitypmid34755108 pmcpmc8573181 doi101093 braincomms fcab229,0.0
methods inclusion realworld evidence network metaanalysis background network metaanalysis nma key component submissions reimbursement agencies worldwide especially limited direct headtohead evidence multiple technologies randomised controlled trials rcts many nmas include data rcts however realworld evidence rwe also becoming widely recognised valuable source clinical data study aims investigate methods inclusion rwe nma impact level uncertainty around effectiveness estimates particular interest effectiveness fingolimodmethodsa range methods inclusion rwe evidence synthesis investigated applying illustrative example relapsing remitting multiple sclerosis rrms literature search identify rcts rwe evaluating treatments rrms conducted assess impact inclusion rwe effectiveness estimates bayesian hierarchical adapted power prior models applied effect inclusion rwe investigated varying degree weighting part evidence use power priorresultswhilst inclusion rwe led increase level uncertainty surrounding effect estimates example depended method inclusion adopted rwe power prior nma model resulted stable effect estimates fingolimod yet increasing width credible intervals increasing weight given rwe data hierarchical nma models effective allowing heterogeneity study designs however also increased level uncertaintyconclusionthe power prior method inclusion rwe nmas indicates degree rwe taken account can significant impact overall level uncertainty hierarchical modelling approach allowed accommodating differences study types consequently work investigating empirical evidence biases associated individual rwe studies methods elicitation experts extent biases warranted,0.0
correction citrullinated native index autoantibodies hnrnpdl predicts individual window treatment success ra patients correction arthritis res ther 23 239 2021 https doiorg 101186 s1307502102603xfollowing publication original article 1 authors reported error additional file 1 wherein track changes visible additional file 1 updatedthe original article 1 updated,0.0
high prevalence vitamin d deficiency among south asian adults systematic review metaanalysis background vitamind deficiency linked wide range chronic infectious diseases body literature suggested prevalence deficiency can geographical variation although vitamin d deficiency frequently reported south asian population scarcity systematic reviews metaanalysis means true extent disease underlying factors causing poorly characterizedmethodsa systematic search performed using two databases pubmed scopus one search engine google scholar original studies south asian population published january 1 2001 december 31 2019 following search random effect metaanalysis performed calculate populationlevel weighted average pooled prevalence deficiency heterogeneity vitamin d among different countries genders addition south asia wholeresultsour study based selection criteria narrowed total 44 717 participants spanned 65 studies five south asian countries overall pooled prevalence deficiency 68 95 ci 64 72 significant heterogeneity i2 98 p 000 average level vitamin d ranged 47 32 ng ml weighted mean 1915 ng ml weighted standard deviation 1159 ng ml highest prevalence vitamin d deficiency found pakistan 73 95 ci 63 83 followed bangladesh 67 95 ci 50 83 india 67 95 ci 61 73 nepal 57 95 ci 53 60 sri lanka 48 95 ci 41 55 respectively finding indicated high degree heterogeneity among population i2 9876 furthermore genderwise analysis suggested south asia prevalence vitamin d deficiency higher females malesconclusionour findings reveal highly prevalent variable vitamin d deficiency among adults different south asian countries findings review helpful generate hypotheses explore factors affecting intercountry variability alongside strengthening evidence governments prioritize mitigation strategies region,0.0
comparison content psychometric properties assessment tools used brain tumor patients scoping review abstractaimsto determine frequently utilized functional status assessment instruments patients brain tumors compare contents using international classification functioning disability health icf psychometric propertiesmethodsa scoping review conducted explore possible assessment instruments summarize evidence systematic literature search performed identification frequently used functional assessment tool clinical trials pubmed sciencedirect proquest databases content used instruments linked icf categories psychometric qualities assessment tools systematically searched analyzedresultsnine used assessment tools clinical trials identified frequently used assessment instrument karnofsky performance scale developed general assessment oncological patients four selfassessment tools two diseasespecific eortc qlqbn20 factbr eortc qlqc30 shown good psychometric properties patients brain tumors well patients various oncological diseases similar sf36 used patients brain tumors well patients various diseases functional independence measure barthel index two objective assessment tools described functioning two neuropsychological tests mmse trial making test two hundred eightythree meaningful concepts identified linked 102 relevant secondlevel categories covering components icf fortynine studies reporting psychometric properties nine assessment tools identified indicating good reliability validity instrumentsconclusionnine frequently utilized functional status assessment instruments patients brain tumors represent components icf good psychometric properties however choice tool depends clinical question posed aim use,0.0
smoking cardiovascular risk factors lrp2 gene variation associations disease severity cognitive function brain structure primary progressive multiple sclerosis abstractbackground smoking cardiovascular risk factors genetic factors can adverse effects msobjective determine smoking disease onset cardiovascular risk factors genetic variants influence primary progressive ms ppms method crosssectional study smoking habits framingham risk score frs genetic variants including lowdensity lipoprotein receptorrelated protein 2 lrp2 snp rs12988804 mri collected 60 ppms trial participants disability cognition assessed agerelated multiple sclerosis severity armss score progressiveonset ms multiple sclerosis severity score brief international cognitive assessment msresults smoking ppms onset significantly associated higher armss 95 ci 0824 p000016 statistically significant bonferroni correction lower magnetization transfer ratio lesions also significantly associated smoking onset ppms 95 ci 0944 p00035 significant bonferroni correction packyears people smoked onset likewise significantly associated higher armss score b006 95 ci 002009 p00021 well lower symbol digit modalities test scores b040 95 ci 066013 p00037 statistically significant bonferroni correction lrp2 risk allele associated decreased performance california verbal learning test 2 cc vs ct+tt 95 ci 14234 p00018 significant bonferroni correction conclusion validated findings suggest intervention regarding smoking may beneficial ppms confirmed assessment lrp2 gene variant may aid understanding underlying pathological mechanisms ppms,0.0
attention timeofday variability improves reproducibility gene expression patterns multiple sclerosis iscience 2021 oct 9 24 11 103247 doi 101016 jisci2021103247 ecollection 2021 nov 19abstractlow reproducibility gene expression profiles observed transcriptome studies often limits applying findings clinical practice show timeofday effects gene expression analytical schemes increase reproducibility expression patterns recruited patients relapsingremitting multiple sclerosis rrms healthy subjects collected blood individuals twice day day 2 pm night 9 pm rna sequencing analyses found gene expression rrms relapse relapse significantly changed night compared either relapse day rrms remission remission gene set overrepresentation analysis demonstrated gene sets significantly changed relapse night enriched immune responses related ms pathology gene sets 68 genes significantly changed expression relapse night compared relapse day remission supports times sample collections standardized obtain reproducible gene expression patternspmid34746708 pmcpmc8551071 doi101016 jisci2021103247,0.0
consensus primary care clinical decisionmaking tool assessing diagnosing managing shoulder pain alberta canada background shoulder pain highly prevalent condition significant cause morbidity functional disability current data suggests many patients presenting shoulder pain primary care level receiving high quality care primary care decisionmaking complex potential influence quality care provided patient outcomes aim study develop clinical decisionmaking tool standardizes care minimizes uncertainty assessment diagnosis managementmethodsfirst rapid review conducted identify existing tools evidence support comprehensive clinical decisionmaking tool shoulder pain secondly provincial consensus established assessment diagnosis management patients presenting primary care shoulder pain alberta canada using threestep modified delphi approach project highly collaborative effort alberta health services bone joint health strategic clinical network bjh scn alberta bone joint health institute abjhi resultsa clinical decisionmaking tool shoulder pain developed reached consensus provincewide expert panel representing various health disciplines geographical regions tool consists clinical examination algorithm assessing diagnosis managing shoulder pain recommendations historytaking identification red flags additional concerns recommendations physical examination neurological screening recommendations differential diagnosis care pathways managing patients presenting rotator cuff disease biceps pathology superior labral tear adhesive capsulitis osteoarthritis instabilityconclusionsthis clinical decisionmaking tool will help standardize care provide guidance diagnosis management shoulder pain assist clinical decisionmaking primary care providers public private sectors,0.0
inflammatory complications cgrp monoclonal antibodies case series background calcitonin generelated peptide cgrp expressed throughout body known mediator migraine exerting biological effect activation trigeminovascular meningeal associated neuronal pathways located close proximity central nervous system monoclonal antibodies mab targeting cgrp pathway effective new preventive treatment migraine generally favourable adverse event profile preclinical evidence supports antiinflammatory immunoregulatory role cgrp organ systems therefore inhibition normal action peptide may promote proinflammatory responsecaseswe present case series eight patients new significantly worsened inflammatory pathology close temporal association commencement cgrp mab therapyconclusionthis case series provides novel insights potential molecular mechanisms sideeffects cgrp antagonism migraine supports clinical vigilance patient care going forward,0.0
prediction multiple sclerosis outcomes switching ocrelizumab abstractbackgroundincreasingly people relapsingremitting multiple sclerosis rrms switched highly effective diseasemodifying therapies dmts ocrelizumabobjectiveto determine predictors relapse disability progression switching another dmt ocrelizumabmethodspatients rrms switched ocrelizumab identified msbase registry grouped prior diseasemodifying therapy pdmt interferon glatiramer acetate dimethyl fumarate teriflunomide fingolimod natalizumab washout duration 1month 12months 26months survival analyses including multivariable cox proportional hazard regression models used identify predictors onocrelizumab relapse within 1year 6month confirmed disability progression cdp resultsafter adjustment relapse hazard switching fingolimod greater pdmts first 3months ocrelizumab therapy hazard ratio hr 398 95 confidence interval ci 1571111 p0004 adjusted hazard cdp significantly higher longer washout 26m compared 1m hr957 95 ci1924764 p0006 conclusionthe risk disability worsening switch ocrelizumab reduced short treatment gaps patients cease fingolimod heightened relapse risk first 3months ocrelizumab prospective evaluation strategies washout reduction may help optimise switch,0.0
magnetically guided theranostics montmorillonitebased iron#x2f platinum nanoparticles enhancing situ mri contrast hepatocellular carcinoma treatment abstractin asia including taiwan malignant tumors hepatocellular carcinoma hcc one liver cancer diagnosed subtype magnetic resonance imaging mri typical diagnostic method accurately diagnosing hcc difficult demonstrate nonenhanced mri tumors radiologists can use contrast agents gd3+ fe3o4 fept t1weighted t2weighted imaging remain liver long time facilitate diagnosis via mri however sometimes difficult t2weighted imaging detect small tumor lesions liver tissue may absorb iron ions makes early cancer detection challenging goal challenge prompted current research create novel nanocomposites enhancing noisetosignal ratio mri develop method can efficiently diagnose simultaneously treat hcc mri examination designed functionalized montmorillonite mmt material porous structure benefit related drugs mitoxantrone mit delivery carrier fept nanoparticles fept nps introduce cancer therapy multifunctional fept mmt can simultaneously visualize hcc enhancing mri signals treating various diseases used inducer magnetic fluid hyperthermia mfh loading drug mit fept mmtmit provides mfh treatment chemotherapy one nanosystem results ultimately prove functionalized fept mmtmit integrated versatile drugs delivery system combining mri chemotheraeutic drugs magnetic guide targeting,0.0
association lipid accumulation product chronic kidney disease chinese community adults report reaction study background limited studies regarding correlation lipid accumulation product lap decreased estimated glomerular filtration rate egfr yielded conflicting findings report demonstrated relationship lap chronic kidney disease ckd defined presence albuminuria decreased egfr purpose study estimate possible correlation lap ckd prevalence chinese community adultsmethodin crosssectional study lap level 7202 participants age 40 years determined possible association ckd evaluated multiple logistic regression modelresultscompared subjects nonckd nonalbuminuria high egfr lap levels significantly increased female male subjects ckd albuminuria low egfr respectively p 0001 univariate logistic regression analysis revealed lap level female male subjects significantly positively associated prevalence ckd p 0001 multivariate logistic regression analysis showed risk ckd prevalence female male subjects progressively increased across lap quartiles p trend 001 risk ckd prevalence subjects q4 significantly increased compared q1 adjustment potential confounding factors models 4 odds ratio 1382 95 confidence intervals ci 10021906 p 005 stratified analysis revealed positive associations lap quartiles risk ckd prevalence people following characteristics women older overweight hypertension normal glucose tolerance appropriate lowdensity lipoprotein cholesterol nonsmokers nondrinkers cardiovascular disease eventsconclusionshigh lap levels might significantly associated risk ckd prevalence communitydwelling chinese female adults may inform public health recommendations clinical practice,0.0
systematic review common genetic variation biological pathways autism spectrum disorder background autism spectrum disorder asd complex neurodevelopmental condition characterized persistent deficits social communication interaction common genetic variation appears play key role development condition systematic review describe relationship genetic variations autism created gene dataset genes involved pathogenesis autism performed overrepresentation analysis evaluate biological functions molecular pathways may explain associations variants development asdresults177 studies gene set composed 139 included qualitative systematic review enriched pathways overrepresentation analysis using kegg pathway database mostly associated neurotransmitter receptors subunits major overrepresented biological processes social behavior vocalization behavior learning memory enriched cellular component proteins encoded genes identified systematic review postsynaptic membrane cell junctionconclusionsamong biological processes examined genes involved synaptic integrity neurotransmitter metabolism cell adhesion molecules significantly involved development autism,0.0
regional brain tissue changes patients cystic fibrosis background cystic fibrosis cf patients present variety symptoms including mood cognition deficits addition classical respiratory autonomic issues suggests brain injury can examined noninvasive magnetic resonance imaging mri manifestation condition however brain tissue integrity sites regulate cognitive autonomic respiratory mood functions cf patients unclear aim assess regional brain changes using highresolution t1weighted images based gray matter gm density t2relaxometry procedures cf control subjectsmethodswe acquired highresolution t1weighted images protondensity pd t2weighted images 5 cf 15 control subjects using 30tesla mri highresolution t1weighted images partitioned gmtissue type normalized common space smoothed using pd t2weighted images wholebrain t2relaxation maps calculated normalized smoothed smoothed gmdensity t2relaxation maps compared voxelbyvoxel groups using analysis covariance covariates age sex spm12 p 0001 resultssignificantly increased gmdensity indicating tissues injury emerged multiple brain regions including cerebellum hippocampus amygdala basal forebrain insula frontal prefrontal cortices various brain areas showed significantly reduced t2relaxation values cf subjects indicating predominant acute tissue changes cerebellum cerebellar tonsil prefrontal frontal cortices insula corpus callosumconclusionscystic fibrosis subjects show predominant acute tissue changes areas control mood cognition respiratory autonomic functions suggests tissue changes may contribute symptoms resulting ongoing hypoxia accompanying condition,0.0
nintedanib idiopathic secondary pleuroparenchymal fibroelastosis background pleuroparenchymal fibroelastosis ppfe variable disease course dismal prognosis majority patients validated drug therapy study evaluate effect nintedanib patients idiopathic secondary ppfe patients admitted tertiary care center 20102019 included retrospective analysis multidisciplinary diagnosis ppfe followedup 3 months lung function tests chest cts available review changes pulmonary function tests assessed using nonparametric tests linear mixed effect model lung volumes measured lobar segmentation using chest ctresultsout 21 patients ppfe nine received nintedanib six received another treatment another six patients monitored without drug therapy annual fvc predicted relative decline 136 134 year nintedanib 16 602 year nintedanib treatment p 0014 whereas significant change fvc relative decline found patients receiving another treatment 1325 34 vs 1661 362 year treatment p 0343 using linear mixed effect model slope fvc 097 month 95 ci 142 052 treatment 050 month 95 ci 088 013 nintedanib difference groups + 047 month 95 ci 016 078 p 0004 decline upper lung volumes measured ct 233 ml year 387 ml year nintedanib 149 ml year 173 ml year nintedanib p 0327 nintedanib tolerability unremarkableconclusionin patients ppfe nintedanib treatment might associated slower decline lung function paving way prospective controlled studies,0.0
mindfulness training brief periods hospitalization multiple sclerosis ms beneficial alterations fatigue mediating role depression abstractobjectivespersons ms pwms frequently affected fatigue depression mindfulnessbased interventions may reduce symptoms pwms consequently application extended various settings efforts made explore effects shortterm mindfulness training brief periods hospitalization current study feasibility potential effects shortterm mindfulness training depression fatigue rumination cognition explored pwms acutecare hospital setting based previous work examined whether relation trait mindfulness fatigue prior following intervention mediated depression whether mediation effect also observable throughout interventionmethodsa shortterm mindfulness training protocol developed tailored requirements acutecare setting subsequently 30 pwms recruited sequentially received mindfulness training routine clinical process median duration hospital eight days number sessions four participants completed relevant selfreport measures depression fatigue rumination neuropsychological assessment trainingresultsparticipants reported significantly increased trait mindfulness decreased depression fatigue following intervention respective change scores highly correlated increased trait mindfulness associated decreased symptoms rumination domain patients reported tendency increased adaptive ability engage distractive behavior arising negative mood measures trait rumination cognition remained relatively stable results mediation analyses indicated depression mediated negative relationship trait mindfulness fatigue symptoms pre post assessments regards change scores association mindfulness cognitive fatigue ceased significant depression controlled albeit case mediation effect reach significanceconclusionresults current study indicate shortterm mindfulness training brief periods hospitalization may beneficial pwms complement previous work identifying depression potential mediator antagonistic relationship mindfulness fatigue based current exploratory study future trials warranted address mechanism mindfulness training detail,0.0
role human endogenous retroviruses hervs multiple sclerosis plausible interplay hervs epsteinbarr virus infection vitamin d abstractmultiple sclerosis ms one chronic inflammatory diseases neurological disability central nervous system cns although exact cause ms still largely unknown genetic environmental factors thought play role disease risk human endogenous retroviruses hervs endogenous viral elements human genome whose expression associated ms hervs normally silenced expressed low levels although expression higher ms healthy population several studies highlighted plausible interaction hervs ms risk factors including viral infection like epsteinbarr viruses vitamin d deficiency may lead high expression hervs patients understanding hervs act scenario can improve understanding towards ms etiology may lead development antiretroviral therapies patients review try examine different hervs expression implicated ms association ebv infection vitamin d status,0.0
epstein barr virus development vaccines immune cell therapy ebvassociated diseases front immunol 2021 oct 8 12734471 doi 103389 fimmu2021734471 ecollection 2021abstractepsteinbarr virus ebv first human tumor virus discovered strongly implicated etiology multiple lymphoid epithelial cancers year ebv associated cancers account 200 000 new cases cancer cause 150 000 deaths worldwide ebv also primary cause infectious mononucleosis 70 adolescents young adults developed countries suffer infectious mononucleosis addition ebv shown play critical role pathogenesis multiple sclerosis ebv prophylactic vaccine induces neutralizing antibodies holds great promise prevention ebv associated diseases ebv envelope proteins including gh gl gb gp350 play key roles ebv entry infection target cells neutralizing antibodies elicited proteins shown prevent ebv infection target cells markedly decrease ebv titers peripheral blood humanized mice challenged lethal dose ebv recent studies demonstrated immunization combination gh gl gb gp350 induced markedly increased synergistic ebv neutralizing activity compared immunization individual proteins previous clinical trials focused gp350 alone partially successful inclusion gh gl gb vaccine formulation gp350 represents promising approach ebv prophylactic vaccine development therapeutic ebv vaccines also tested clinically encouraging results immunization various vaccine platforms expressing ebv latent proteins ebna1 lmp1 lmp2 promoted specific cd4+ cd8+ cytotoxic responses antitumor activity addition ebv envelope proteins gh gl gb gp350 potential increase efficacy therapeutic ebv vaccine immune system plays critical role control tumors immune cell therapy emerged promising treatment cancers adoptive tcell therapy successfully used prevention treatment posttransplant lymphoproliferative disorder chimeric antigen receptor t cell therapy t cell receptor engineered t cell therapy targeting ebv latent proteins lmp1 lmp2 ebna1 development goal increase specificity efficacy treatment ebv associated cancerspmid34691042 pmcpmc8532523 doi103389 fimmu2021734471,0.0
role b cell profile predicting secondary autoimmunity patients treated alemtuzumab front immunol 2021 oct 8 12760546 doi 103389 fimmu2021760546 ecollection 2021abstractobjective explore baseline blood lymphocyte profile identify relapsing remitting multiple sclerosis rrms patients higher risk developing secondary autoimmune adverse events aiaes alemtuzumab treatmentmethods multicenter prospective study including 57 rrms patients treated alemtuzumab followed 325 35421 years median interquartile range blood samples collected baseline leukocyte subsets determined flow cytometry additional samples one year first cycle alemtuzumab treatment 39 casesresults twentytwo patients 386 developed aiaes followup higher bcell percentages baseline p00014 differences mainly due plasmablasts plasma cells pb pc p00011 aiaes higher percentages cd4+ t cells p0013 mainly due terminally differentiated td p0034 effector memory em p0031 phenotypes aiaes patients also showed higher values tnfalphaproducing cd8+ t cells p0029 percentage pb pc best variable differentiate groups patients baseline values 010 closely associated higher aiae risk odds ratio 591 95 ci 1831910 p0004 excluding 12 patients natalizumab decreases blood pb pc percentages last treatment alemtuzumab baseline pb pc 01 even predicted accurately risk aiaes 1167 95 ci 2625189 p00007 aiaes+ group continued high percentages pb pc year alemtuzumab treatment p00058 conclusions pb pc percentage 01 baseline identifies ms patients low risk secondary autoimmunity alemtuzumab treatmentpmid34691084 pmcpmc8531491 doi103389 fimmu2021760546,0.0
impact coronavirus disease 2019 pandemicrelated interruption regular physical rehabilitation functional abilities patient two chronic neurological diseases case report background regular outpatient rehabilitation prescribed many patients chronic neurological disorders parkinsons disease multiple sclerosis constantly support patients proxies disease management due coronavirus disease 2019 pandemic federal institutions governments worldwide directed local nationwide lockdowns times provision regular outpatient rehabilitation service drastically limited making actually impossible communitydwelling patients neurological disorders receive prescribed rehabilitation interventionscase presentationa 67yearold white swiss man two chronic neurological diseases parkinsons disease multiple sclerosis underwent 4week inpatient rehabilitation hospital main rehabilitation goals related improvements mobility decrease risk falls patient gained significant functional improvements maintained following months supported continuation physiotherapy domestic environment due coronavirus disease 2019 pandemicrelated interruption regular ambulatory rehabilitation several weeks first coronavirus disease 2019 wave switzerland patients functional abilities decreased significantly thus patient referred hospital intensive inpatient rehabilitation regain physical functioning mobility capacity hospital discharge patient improved physical functioning prepandemic levelconclusionsthe interruption rehabilitation service due pandemicrelated lockdown can significantly impact functional abilities patients chronic neurological diseases case report supports claim continuous access rehabilitation services people rehabilitation needs,0.0
central neuropathic pain multiple sclerosis associated impaired innocuous thermal pathways neuronal hyperexcitability pain med 2021 mar 18pnab103 doi 101093 pm pnab103 online ahead printabstractobjective third patients multiple sclerosis ms suffer chronic excruciating central neuropathic pain cnp mechanism underlying cnp ms clear since previous studies scarce results inconsistent aim determine whether cnp ms associated impairment spinothalamicthalamocortical pathways sttcs increased excitability pain systemdesign cross sectional studysetting general hospitalsubjects 47 ms patients cnp 42 ms patients without cnp 32 healthy controlsmethods sensory testing included measurement temperature pain touch thresholds thermal grill illusion tgi evaluating sttcs function hyperpathia allodynia indicators hyperexcitability cnp characterized using interviews questionnairesresults cnp group higher cold warm thresholds p 001 well higher tgi perception thresholds p 005 especially painful body regions compared controls whereas touch pain thresholds values normal cnp group also significantly greater prevalence hyperpathia allodynia regression analysis revealed whereas presence cnp associated higher cold threshold cnp intensity number painful body regions associated allodynia hyperpathia respectivelyconclusions cnp ms characterized specific impairment sttc function innocuous thermal pathways pain hyperexcitability whereas cnp presence associated sttc impairment severity extent associated pain hyperexcitability interventions reduce excitability level may therefore mitigate cnp severitypmid33734398 doi101093 pm pnab103,0.0
azd8055 ameliorates experimental autoimmune encephalomyelitis via mtor ros nlrp3 pathway biochem biophys res commun 2021 aug 6 5732734 doi 101016 jbbrc202108010 online ahead printabstractaims experimental autoimmune encephalomyelitis eae mouse model multiple sclerosis ms characterized immunemediated demyelination neurodegeneration nodlike receptor protein 3 nlrp3 inflammasome activation aggravates spinal cord inflammation eae autophagy associated alleviation systemic inflammation including encountered eae however effects autophagy nlrp3 eae still unclear evaluated effects autophagy activator azd8055 eaemethods eae model mice established histological examination performed assess degree inflammatory cell infiltration demyelination levels autophagy nlrp3mediated pyroptosis spinal cords assessed western blotting immunofluorescence analyses performed evaluate protein expression localizationresults azd8055 significantly enhanced autophagy spinal cords eae model mice coupled decreased abnormal clinical behavior scores increased body weights degree inflammatory cell infiltration demyelination mild azd8055treated eae model micemeanwhile pathway ros nlrp3 downregulated lc3 nlrp3 colocalizedconclusions azd8055 ameliorated eae antiinflammatory antipyroptosis effects via mammalian target mtor ros nlrp3 pathway findings provide insights interactions autophagy pyroptosis may facilitate development novel treatments mspmid34384953 doi101016 jbbrc202108010,1.0
prevalence overactive bladder symptoms impact healthrelated quality life medical dentistry students multicenter crosssectional study background overactive bladder oab popular distressing health condition negative impact healthrelated quality life hrqol inflicted individuals multicenter study conducted determine prevalence oab symptoms impact hrqol medical dentistry studentsmethodsthis study conducted crosssectional design 3 main universities palestine addition sociodemographic health academic characteristics medical dentistry students questionnaire also contained oab symptom bother 6items hrqol 13items shortform oabq sf scales kruskalwallis test mannwhitney u test pearson chisquare fishers exact test spearmans rank correlations multiple linear regression model used analyze dataresultsresponses collected medical dentistry students n 402 median oab symptom bother score 541 448 819 median hrqol score 944 884 944 strong negative correlation oab hrqol scores spearmans rho 644 p value 0001 oab scores significantly higher among dentistry students females chronic disease reported stressful life hrqol scores significantly higher among medicine students reported less stressful life reported satisfaction social life dentistry students female selfreported high stress 194fold 95 ci 105 356 191fold 95 ci 116 314 188fold 95 ci 121 291 likely report less optimal hrqol compared medicine students male selfreported low stress respectivelyconclusionsour findings suggested oab symptoms prevalent among medical dentistry students across palestinian universities decision makers academia healthcare authorities advocacy groups might need design appropriate interventions address health wellbeing issues medical dentistry students using appropriate diagnostic procedures reducing stress improving social life might help reducing burden oab improve hrqol medical dentistry students investigations conducted investigate interventions effective reducing oab symptoms improving hrqol,0.0
association neutrophiltolymphocyte ratio nlr prognosis first attack neuromyelitis optica spectrum disorder nmosd retrospective cohort study background investigate relationship neutrophiltolymphocyte ratio nlr prognosis first attack optic neuromyelitis optica spectrum disorder nmosd methodsin retrospective study included medical records 324 patients first episode nmosd collected data clinical parameters followup extended disability status scale edss score relapse rate analyzed using logistic regression models determine independent effect nlr outcomes receiver operating characteristic roc curves applied analyze predictive value nlr prognosis nmosd interaction stratification analyses used explore association nlr prognosis patients nmosd kaplanmeier analysis used investigate relationship nlr outcome association nlr level relapse rate poor recovery assessed cox regression analysisresultspatients highnlr group significantly higher edss scores relapse rates followup p 0001 lownlr group univariate analysis showed revealed nlr significantly associated relapse odds ratio 128 95 confidence interval ci 116141 p 0001 poor recovery 132 95 ci 120146 p 0001 associations remained significant even multifactorial analysis 133 95 ci 111159 p 0002 123 95 ci 106143 p 0007 respectively stratified analysis showed sex platelettolymphocyte ratio plr level lymphocytetomonocyte technical ratio lmr level strongly associated relapse owing elevated nlr kaplanmeier survival curve analysis showed median time relapse significantly lower highnlr group lownlr group p 0001 multivariate analysis showed significant relationship nlr level relapse hr 107 95ci 103110 p 0001 poor recovery hr 108 95ci 104111 p 0001 conclusionsnlr may used prognostic indicator first onset nmosd high nlr may significantly associated high relapse rates poor recovery,0.0
cardiac ectopic lymphoid follicle formation viral myocarditis involving regulation podoplanin th17 cell differentiation abstractautoimmunity contributes pathogenesis viral myocarditis vmc characterized production antiheart autoantibodies aha lymphoid follicles recently formation ectopic lymphoid follicles elfs reported heart grafts however existence role elfs myocardial tissues vmc remain unclear study aimed explore whether cardiac elfs germinal centers gcs generated development vmc identified existence elfs explored underlying mechanism balb c mouse model vmc dynamic myocardial infiltrations lymphocytic aggregates expressions associated lymphorganogenic factors investigated accompanied detection production location myocardial aha data indicated elfs formation myocardial tissues vmc number elfs accordance severity vmc moreover functional elfs gcs capable facilitating production local aha blocking il17 podoplanin pdpn inhibit cardiac elfs generation perhaps due negative regulation pdpn neutralization th17 cell proliferation differentiation presence cardiac elfs aha might offer new opportunities stratification early identification vmc patients,0.0
trajectories sickness absence disability pension days among people multiple sclerosis type occupation abstractbackgroundmultiple sclerosis ms can impact working life sickness absence sa disability pension dp different types occupations involve different demands may associated trajectories sa dp among people ms pwms objectivesto explore among pwms references sa dp differ according type occupation furthermore examine trajectories sa dp days associated type occupation among pwmsmethodsa longitudinal nationwide swedish registerbased cohort study conducted including 6100 individuals prevalent ms 38 641 matched references population trajectories sa dp identified groupbased trajectory modelling multinomial logistic regressions estimated associations identified trajectories occupationsresultsincrease sa dp time observed occupational groups pwms references higher levels sa dp among pwms lowest levels sa dp observed among managers three trajectory groups sa dp identified persistently low 552 moderate increasing 319 high increasing 128 managers working science technology economics social cultural likely belong persistently low groupconclusionresults suggest type occupation plays role level course sa dp,0.0
reappraisal csfspecific oligoclonal bands asia abstractthe prevalence cerebrospinal fluidspecific oligoclonal bands csfocbs reported low asian people multiple sclerosis pwms compared western pwms yet determined whether genuine feature asian pwms misapprehension owing past misclassification msmimicking diseases ms aimed reappraise prevalence csfocbs korean pwms carefully excluding central nervous systeminflammatory demyelinating diseases since 2017 among 88 subjects 78 886 positive csfocbs suggests prevalence csfocbs different korean western pwms,1.0
18ffdg positron emission tomography#x2f computed tomography pet#x2f ct distinguishing tuberous sclerosis complex lesions colon cancer metastases j case rep 2021 oct 7 22e933320 doi 1012659 ajcr933320abstractbackground tuberous sclerosis complex tsc bournevillepringle disease multisystem genetic disorder manifesting benign tumors can affect system malignant neoplasm may coexist patients tsc cases diagnostic difficulties distinguishing metastatic lesions benign changes show usefulness positron emission tomography pet resolving difficulties case report purpose article present usefulness metabolic imaging using 18ffluorodeoxyglucose positron emission tomography computed tomography 18ffdg pet ct distinguishing benign neoplastic lesions patient tsc 17yearold female patient tsc referred 18ffdg pet ct suspected lung bone metastases patient underwent bilateral nephrectomy multiple cysts angiomyolipomas colonoscopy performed preparation kidney transplantation revealed sevearal colon polyps one found cancerous upon histopathologic examination diagnosis adenocarcinoma g3 made ct scan chest abdomen performed afterwards showed multiple pulmonary nodules sclerotic bone lesions suggestive metastases two 18ffdg pet ct scans performed within 6 months showed multiple nodules 715 mm diameter changes typical multifocal micronodular pneumocyte hyperplasia lungs bones found multiple sclerotic lesions findings showed fdg uptake level background activity contradicted lesions metastatic origin conclusions using example 17yearold patient tsc present usefulness metabolic imaging using 18ffdg pet ct distinguishing benign neoplastic lesionspmid34618793 doi1012659 ajcr933320,0.0
linking immunemediated damage neurodegeneration multiple sclerosis networkbased mri help brain commun 2021 oct 7 3 4 fcab237 doi 101093 braincomms fcab237 ecollection 2021abstractinflammatory demyelination characterizes initial stages multiple sclerosis progressive axonal neuronal loss coexisting significantly contribute longterm physical cognitive impairment unmet need conceptual shift dualistic view multiple sclerosis pathology involving either inflammatory demyelination neurodegeneration integrative dynamic models brain reorganization glianeuron interactions synaptic alterations grey matter pathology longitudinally envisaged wholebrain level functional structural mri can delineate network hallmarks relapses remissions disease progression can linked pathophysiology behind inflammatory attacks repair neurodegeneration aim unify recent findings grey matter circuits dynamics multiple sclerosis within framework molecular pathophysiological hallmarks combined diseaserelated network reorganization highlighting advances animal models vivo ex vivo human clinical data imaging histological propose mribased brain networks characterization essential better delineating ongoing pathology elaboration particular mechanisms may serve accurate modelling prediction disease courses throughout disease stagespmid34729480 pmcpmc8557667 doi101093 braincomms fcab237,1.0
chronic use hydroxychloroquine protect covid19 large cohort patients rheumatic diseases brazil background lack information role chronic use hydroxychloroquine sarscov2 outbreak aim compare occurrence covid19 rheumatic disease patients hydroxychloroquine individuals household taking drug first 8 weeks community viral transmission brazil methodsthis baseline crosssectional analysis part 24week observational multicenter study involving 22 brazilian academic outpatient centers information regarding covid19 symptoms epidemiological clinical demographic data recorded specific webbased platform using telephone calls physicians medical students covid19 defined according brazilian ministry health bmh criteria mannwhitney chisquare exact fisher tests used statistical analysis two binary final logistic regression model wald test developed using backwardstepwise method presence covid19resultsfrom march 29th may 17st 2020 total 10 443 participants enrolled including 5166 539 rheumatic disease patients 825 systemic erythematosus lupus 78 rheumatoid arthritis 37 sjgrens syndrome 08 systemic sclerosis total 1822 191 participants reported flu symptoms within 30 days prior enrollment 31 fulfilled bmh criteria significant difference rheumatic disease patients 403 controls 325 adjustments multiple confounders main risk factor significantly associated covid19 diagnosis lung disease 163 95 ci 103258 rheumatic disease patients diagnosis systemic sclerosis 28 95 ci 119663 glucocorticoids 10 mg day 205 95 ci 131319 addition recent influenza vaccination protective effect 0674 95 ci 046098 conclusionpatients rheumatic disease hydroxychloroquine presented similar occurrence covid19 household cohabitants suggesting lack protective role sarscov2 infectiontrial registration brazilian registry clinical trials rebec rbr 9ktwx6,0.0
sub internal limiting membrane hemorrhage followed bilateral optic disc hemorrhage kikuchifujimoto disease case report background kikuchifujimoto disease kfd necrotizing lymphadenitis presents fever unknown origin cervical lymphadenopathy ocular complications unusual kfd report case sub internal limiting membrane ilm hemorrhage followed bilateral optic disc hemorrhage kfdcase presentationa 16yearold japanese man perceived sudden decrease right vision 3 days onset fever unknown origin left cervical lymphadenopathy presentation visual acuity va right eye 005 decimal chart 130 converted logarithm minimum angle resolution logmar fundus photograph showed extensive subilm hemorrhage right eye optic disc hemorrhages eyes fluorescein angiography presented hypo hyperfluorescences optic disc right eye hyperfluorescence disc left eye make definitive diagnosis cervical lymph node biopsy performed kfd diagnosed pathologically thereafter fever headache cervical lymphadenopathy disappeared spontaneously subilm hemorrhage drained vitreous cavity neodymiumyttriumaluminumgarnet laser nd yag hyaloidotomy va recovered 15 018 logmar va right eyeconclusionsubilm hemorrhage optic disc hemorrhage kfdrelated ocular complication,0.0
healthrelated benefits adverse events associated yoga classes among participants healthy poor health chronic diseases background previous study demonstrated 42 yoga class participants japan chronic diseases requiring medication raises question whether chronic diseases benefit practicing yoga higher risk specific adverse events compared healthy individuals receiving instructionmethodsto address questions 328 adults started practicing yoga first time asked complete profile mood states poms perceived stress scale pss medical outcomes study short form 8 standard version sf8 record adverse events first day yoga class three months later participants consisted three groups healthy h group n 70 poor health ph group n 117 chronic disease cd group n 141 degree subjective symptoms also compared pre postintervention period ph cd groupsresultstypically yoga classes held week 6090 min programs included asanas pranayamas meditation isometric yoga sukshma vyayama ph cd groups poms tensionanxiety fatigue scores decreased vigor score increased significantly first class furthermore pss scores decreased sf8 scores increased significantly three months later degree subjective symptoms easy fatigability shoulder stiffness insomnia also decreased three months individuals groups experienced frequent adverse events h group ph cd groups also experienced greater variety symptoms including psychological ones reported h group adverse events serious participants stopped practicing yoga class 60 participants highly satisfied participating yoga classesconclusionsif yoga classes conducted attention possible adverse events yoga practice yoga studio may beneficial effects people functional somatic symptoms chronic diseases well healthy participants benefits include reductions perceived stress uncomfortable symptoms well improved mood quality life,0.0
crosstalk microorganisms immune responses autoimmune neuroinflammation focus regulatory t cells front immunol 2021 oct 7 12747143 doi 103389 fimmu2021747143 ecollection 2021abstractregulatory t cells tregs major determinant peripheral immune tolerance many treg subsets described however thymusderived peripherally induced tregs remain important subpopulations multiple sclerosis prototypical autoimmune disorder central nervous system treg dysfunction pathogenic hallmark contrast induction treg proliferation enhancement function central immune evasion mechanisms infectious pathogens accordance treg expansion compartmentalized tissues high viral replication prolonged chronic infections friend retrovirus infection treg expansion mainly based excessive interleukin2 production infected effector t cells moreover pathogens seem also enhance treg functions shown human immunodeficiency virus infection tregs express higher levels effector molecules cytotoxic tlymphocyteassociated protein 4 cd39 camp show increased suppressive capacity thus insights molecular mechanisms intracellular pathogens alter treg functions might aid find new therapeutic approaches target central nervous system autoimmunity review summarize current knowledge role pathogens treg function context autoimmune neuroinflammation discuss mechanistic implications future therapies provide outlook new research directionspmid34691057 pmcpmc8529161 doi103389 fimmu2021747143,0.0
covid19 multiple sclerosis clinically reported outcomes uk multiple sclerosis register abstractbackground march 2020 united kingdom multiple sclerosis register ukmsr established electronic case return form designed collaboratively ms neurologists record data covid19 infections people ms pwms objectives examine hospital admission mortality affected disability age disease modifying treatments dmts people multiple sclerosis covid19methods anonymised data submitted clinical teams regression models tested predictors hospitalisation mortality outcomes separate analyses compared first second wavesnull pandemicresults univariable analysis found hospitalisation mortality associated increasing age male gender comorbidities severe disability progressive ms severe disability showed highest magnitude association dmt associated small lower risk multivariable analysis found age male gender significant post hoc analysis demonstrated factors significant hospitalisation mortality second wave hospitalisation mortality lower separate models first second wave using age gender found important role second waveconclusions features associated poor outcome covid19 similar populations dmt found associated adverse outcomes consistent smaller studies hospital factors predictive mortality reassuringly mortality appears lower second wave,0.0
scfd1 expression quantitative trait loci amyotrophic lateral sclerosis differentially expressed brain commun 2021 oct 7 3 4 fcab236 doi 101093 braincomms fcab236 ecollection 2021abstractevidence indicates common variants found genomewide association studies increase risk disease gene regulation via expression quantitative trait loci using multiple genomewide methods examined single nucleotide polymorphisms increase risk amyotrophic lateral sclerosis expression quantitative trait loci whether expression quantitative trait loci expression consistent across people amyotrophic lateral sclerosis combining public expression quantitative trait loci data amyotrophic lateral sclerosis genomewide association studies used summarydatabased mendelian randomization confirm scfd1 gene genomewide significant mediating amyotrophic lateral sclerosis risk via expression quantitative trait loci summarydatabased mendelian randomization beta 020 standard error 004 pvalue 429 106 using postmortem motor cortex tested whether expression quantitative trait loci showed significant differences expression amyotrophic lateral sclerosis n 76 controls n 25 genomewide 20 757 genes analysed two significant expression quantitative trait loci show differential expression amyotrophic lateral sclerosis controls involve two known amyotrophic lateral sclerosis genes scfd1 vcp cisacting scfd1 expression quantitative trait loci downstream gene showed significant differences expression amyotrophic lateral sclerosis controls top expression quantitative trait loci beta 034 standard error 0063 pvalue 454 107 scfd1 expression quantitative trait loci also significantly modified amyotrophic lateral sclerosis survival number samples 4265 hazard ratio 111 95 confidence interval 105117 pvalue 206 104 act amyotrophic lateral sclerosis transexpression quantitative trait loci hotspot wider network genes enriched scfd1 function amyotrophic lateral sclerosis pathways using geneset analyses found genes correlate transexpression quantitative trait loci hotspot significantly increase risk amyotrophic lateral sclerosis beta 0247 standard deviation 0017 p 0001 schizophrenia beta 0263 standard deviation 0008 pvalue 118 105 disease genetically correlates amyotrophic lateral sclerosis summary scfd1 expression quantitative trait loci major factor amyotrophic lateral sclerosis influencing disease risk differentially expressed postmortem amyotrophic lateral sclerosis scfd1 expression quantitative trait loci show distinct expression profiles amyotrophic lateral sclerosis correlate wider network genes also confer risk disease modify diseases durationpmid34708205 pmcpmc8545614 doi101093 braincomms fcab236,0.0
adipokines immune cell modulators multiple sclerosis int j mol sci 2021 oct 7 22 19 10845 doi 103390 ijms221910845abstractmultiple sclerosis ms chronic inflammatory demyelinating disease central nervous system cns major clinical societal problem tremendous impact life patients proxies current immunomodulatory antiinflammatory therapies prove relatively effective however fail concomitantly stop ongoing neurological deterioration reverse acquired disability proportion genetic environmental factors contribute etiology ms still incompletely understood however recent association ms etiology obesity shown obesity greatly increasing risk developing ms altered balance adipokines white adipose tissue wat hormones plays important role lowgrade chronic inflammation obesity pervasive modification local systemic inflammation vice versa inflammatory factors secreted immune cells affect adipokine function explore role adipokines ms pathology will review reciprocal effects adipokines immune cells summarize alterations adipokine levels ms patient cohorts finally will discuss proofofconcept studies demonstrating therapeutic potential adipokines target neuroinflammation neurodegeneration processes mspmid34639186 doi103390 ijms221910845,1.0
impact covid19 pandemic mental health wellbeing people living longterm physical health condition qualitative study background covid19 pandemic associated restrictions caused major global disruption individuals longterm physical health conditions ltcs higher risk severe illness often subject strictest pandemic guidance may disproportionally affected aim study qualitatively explore living ltc covid19 pandemic affected peoples mental health wellbeingmethodsparticipants people living ltcs participated telephone video call interviews based semistructured topic guide key themes subthemes determined using deductive inductive thematic analysisresultsthe sample included 32 participants ltcs commonly cancer respiratory conditions cardiovascular diseases mean age 57 sd 13 years 66 female 72 white british four overarching themes specific living ltc 1 high levels fear anxiety related perceived consequences catching covid19 2 impact shielding isolation mental health wellbeing 3 experience healthcare pandemic 4 anxiety created uncertainty future fourteen subthemes identified including concerns accessing essential supplies importance social support individuals lived alone advised shield profoundly negatively affectedconclusionsthis study found number aspects living ltc pandemic significant impact mental health wellbeing focus best provide practical social support people ltcs pandemic particularly shield isolate,0.0
significance diagnosis executive functions patients relapsingremitting multiple sclerosis int j environ res public health 2021 oct 7 18 19 10527 doi 103390 ijerph181910527abstractmultiple sclerosis ms progressive chronic disease central nervous system cns cognitive decline occurs rather rarely relapsingremitting multiple sclerosis rrms compared types present study aimed assess executive functions ef relation clinical demographic variables patients rrms study involved 22 individuals rrms aged 23 49 years 22 matching controls individuals rrms remission phase assessments carried using moca bdiii halstead category test porteus maze test verbal fluency tasks stroop colourword interference test findings show two groups differed significantly tests patients rrms remission phase presented least one cognitive deficit observed general cognitive functioning abstract reasoning executive functions ie fluency interference suppression planning ability modify activity response feedback deficits cases except measured moca category tests phonemic fluency related intensity depression duration disease findings suggest diagnostic process case patients rrms may include psychological assessment focusing potentially existing cognitive mainly executive deficits severitypmid34639827 doi103390 ijerph181910527,0.0
measurement neurofilaments improves stratification future disease activity early multiple sclerosis abstractbackgroundthe added value neurofilament light chain levels serum snfl concept evidence disease activity3 neda3 yet investigated detailobjectiveto assess whether combination snfl neda3 status improves identification patients higher risk disease activity following yearmethodswe analyzed 369 blood samples 155 early relapsingremitting ms patients interferon beta1a compared disease activity including rate brain volume loss subgroups defined neda3 status high low snfl 90th or90th percentile resultsin patients disease activity eda3 higher snfl higher odds eda3 following year low snfl 865 vs 579 or425 95 ci 202 895 p00001 greater whole brain volume loss following year 036 95 ci 060 013 p0002 accordingly neda3 patients high snfl showed numerically higher disease activity eda3 following year compared low snfl 571 vs 311 conclusionsnfl improves ability identify patients higher risk future disease activity beyond neda3 status measurement snfl may assist clinicians decisionmaking providing sensitive prognostic information,0.0
multiple sclerosis diagnosis knowledge gaps opportunities educational intervention neurologists united states abstractbackgroundfew studies addressed results educational efforts concerning proper use mcdonald criteria mc revisions outside multiple sclerosis ms subspecialty centers neurology residents ms subspecialist neurologists demonstrated knowledge gaps core elements mc recent prior studyobjectiveto assess comprehension application mc core elements nonms specialist neurologists united states routinely diagnose msmethodsthrough crosssectional study design previously developed survey instrument distributed onlineresultsa total 222 neurologists completed study survey syndromes atypical ms frequently incorrectly considered typical ms presentations fourteen percent correctly identified definitions periventricular juxtacortical lesions 2 correctly applied terms 9 9 images twentyfour percent correctly identified four central nervous system cns regions satisfaction magnetic resonance imaging mri dissemination space two presented cases 61 71 correctly identified dissemination time dit fulfilled 85 86 subsequently accepted nonspecific historical symptoms without objective evidence dit fulfillmentconclusionthe high rate knowledge deficiencies application errors core elements mc demonstrated participants study raise pressing questions concerning adequacy dissemination educational efforts upon publication revisions mc,0.0
interpreting change symbol digit modalities test people relapsing multiple sclerosis using reliable change methodology abstractbackgroundthe symbol digit modalities test sdmt increasingly utilized clinical trials sdmt score change 4 points considered clinically important based association employment anchors optimal thresholds statistically reliable sdmt changes accounting test reliability measurement error yet applied individual casesobjectivethe aim study derive statistically reliable marker individual change sdmtmethodsthis prospective casecontrol study enrolled 166 patients multiple sclerosis ms sdmt scores baseline relapse 3month followup compared relapsing stable patient groups using data stable group three previously published studies candidate thresholds reliable decline calculated validated tests clinically meaningful anchorcognitive relapseresultscandidate thresholds reliable decline 80 confidence level varied 6 11 points sdmt change 8 raw score points deemed offer best balance discriminatory power external validity estimating cognitive declineconclusionthis study illustrates feasibility usefulness reliable change methodology identifying statistically meaningful cognitive decline implemented identify change individual patients clinical management clinical trial outcomes,0.0
recombinant glucocorticoidinduced leucine zipper protein ameliorates symptoms dextran sulfate sodiuminduced colitis improving intestinal permeability abstractinflammatory bowel diseases ibds chronic inflammatory disorders characterized relapsing intestinal inflammation many details pathogenesis remain fully unraveled glucocorticoid gc induced leucine zipper gilz mediator antiinflammatory effects gcs powerful drugs ibd treatment cause several unwanted side effects fusion protein tatgilz successfully used preclinical models inflammatory autoimmune diseases test efficacy tatgilz treating dextran sulfate sodium dss induced colitis explore impact gut microbiome colitis induced dss c57bl 6j mice treated tatgilz dexamethasone various hallmarks colitis analyzed including disease activity index gut permeability expression proinflammatory cytokines tight junction proteins tatgilz treatment showed therapeutic effect administered onset colitis efficacy associated improved gut permeability evidenced zonula occludens1 cd74 upregulation inflamed colonic tissue tatgilz also ameliorated changes gut microbiota induced dss thus potentially providing optimal environment colonization mucosa surface beneficial bacteria overall results demonstrated first time tatgilz treatment proved effective disease onset allowing restoration gut permeability key pathogenic feature colitis additionally tatgilz restored gut dysbiosis thereby contributing healing mechanisms interestingly found unprecedented effects exogenous gilz overlap gcs,0.0
oligodendroglial ring finger protein rnf43 essential injuryspecific regulator oligodendrocyte maturation neuron 2021 aug 5s08966273 21 005390 doi 101016 jneuron202107018 online ahead printabstractoligodendrocyte ol maturation arrest human white matter injury contributes significantly failure endogenous remyelination multiple sclerosis ms newborn brain injuries hypoxic ischemic encephalopathy hie cause cerebral palsy study identify oligodendroglialintrinsic factor controls ol maturation specifically setting injury find requirement ring finger protein rnf43 normal development neonatal hypoxic injury remyelination adult mammalian cns rnf43 related znrf3 potently activated wnt signaling ol progenitor cells opcs marks activated opcs human ms hie rnf43 required injuryspecific context promotes opc differentiation negative regulation wnt signal strength opcs level fzd1 receptor presentation cell surface inhibition fzd1 using um206 promotes remyelination following ex vivo vivo demyelinating injurypmid34390652 doi101016 jneuron202107018,1.0
online clinical pathway chronic kidney disease management primary care retrospective cohort study background clinical pathways aim improve patient care sought determine whether online chronic kidney disease ckd clinical pathway associated improvements ckd managementmethodswe conducted retrospective pre post populationbased cohort study using linked health data alberta canada included adults 18 years older mean estimated glomerular filtration rate egfr 60 ml min 173m2 primary outcome measurement outpatient urine albumin creatinine ratio acr 28day period among people without test prior year secondary outcomes included use guidelinerecommended drug therapies angiotensinconverting enzyme inhibitors angiotensin receptor blockers statins resultsthe study period spanned october 2010 march 2017 84 independent 28day periods 53 pre 31 post pathway implementation including 345 058 adults population predominantly female 56 median age 77 years category 3a ckd 67 hypertension 82 adjusted segmented regression models increase rate change acr testing greatest calgary zone adjusted 119 per year 95 ci 116121 dissemination pathway strongest increase pronounced without diabetes adjusted 125 per year 95 ci 121129 small improvements guidelineconcordant medication use also observedconclusionsfollowing implementation online ckd clinical pathway improvements acr testing evident regions pathway actively used particularly among individuals without diabetes,0.0
infections multiple sclerosis world sardinia sardinia world front immunol 2021 oct 6 12728677 doi 103389 fimmu2021728677 ecollection 2021abstractmultiple sclerosis ms inflammatory disease central nervous system sardinia italian island one areas highest global prevalence ms genetic factors widely explored explain greater prevalence among populations genetic makeup sardinians appears make likely develop autoimmune diseases strong association ms infections reported globally robust evidence indicating role infections ms development concerns epsteinbarr virus ebv antiebv antibodies patients infected ebv associated development ms years later features also noted sardinian patients ms many groups found increased expression human endogenous retroviruses herv family patients ms role pathogenesis prognosis prediction treatment response proposed herv european multicentre study shown presence variable among populations ranging 59 100 patients higher herv expression noted sardinian patients ms mycobacterium avium subspecies paratuberculosis map dna antibodies map2694 protein found associated ms sardinian patients recently association also reported japanese patients ms study analysed role infectious factors sardinian patients ms compared findings reported populationspmid34691035 pmcpmc8527089 doi103389 fimmu2021728677,0.0
multiple sclerosis progression discussion tool usability usefulness clinical practice crosssectional webbased survey j med internet res 2021 oct 6 23 10 e29558 doi 102196 29558abstractbackground digital tool multiple sclerosis progression discussion tool msprodiscuss developed facilitate discussions health care professionals hcps patients evaluating early subtle signs multiple sclerosis ms disease progressionobjective aim study report findings usability usefulness msprodiscuss realworld clinical settingmethods crosssectional webbased survey hcps across 34 countries completed initial individual questionnaire comprising 7 questions comprehensibility usability usefulness using msprodiscuss patient consultation final questionnaire comprising 13 questions comprehensibility usability usefulness integration adoption clinical practice capture hcps overall experience using tool responses provided 5point likert scale analyses descriptive statistical comparisons maderesults total 301 hcps tested tool 6974 people ms 77 5370 6974 relapsingremitting ms including suspected transitioning secondary progressive ms time taken complete msprodiscuss reported range 1 4 minutes 973 6786 6974 initial 982 269 274 final cases 9354 6524 6974 initial 971 266 274 final cases hcps agreed 4 5 likert scale patients able comprehend questions tool hcps willing use tool patient 9047 6310 6974 initial cases hcps reported msprodiscuss useful discussing ms symptoms impact daily activities 6121 6974 8776 initial 252 274 92 final cognitive function 5482 6974 7861 initial 271 274 792 final well discussing progression general 6102 6974 8749 initial 246 274 898 final completing final questionnaire 949 260 274 hcps agreed questions similar asked regular consultation tool helped better understand impact ms symptoms daily activities 249 274 909 cognitive function 220 274 803 overall 92 252 274 hcps reported recommend msprodiscuss colleague 858 235 274 willing integrate clinical practiceconclusions msprodiscuss usable useful tool facilitate physicianpatient discussion ms disease progression daily clinical practice hcps agreed tool easy use willing integrate msprodiscuss daily clinical practicepmid34612826 doi102196 29558,0.0
predictors cognitive fatigue fatigability multiple sclerosis abstractbackground persons multiple sclerosis pwms commonly experience cognitive fatigue cf defined decrease cognitive performance sustained activity yet cf remains understudied relationship subjective cf objective cf cognitive fatiguability fully elucidated previous studies understanding predictors cognitive fatigue may scaffold development interventions target symptom objective prospective study evaluate extent depression anxiety information processing speed sleep quality predict subjective objective cfmethods pwms recruited one academic ms clinic london canada objective cf measured paced auditory serial addition test pasat performance last third pasat compared performance 1st third validated measurement objective cf subjective cf measured cognitive component modified fatigue impact scale mfis additionally depression anxiety information processing speed sleep quality data collected assessments took place day pearsonnulls r calculated examine relationship among continuous outcome measures linear regression analyses used examine predictors subjective objective cfresults sample consisted 53 subjects mostly female 37 698 mean age 442 years majority 47 887 relapsing ms objective cf subjective cf significantly related r16 statistically significant predictors objective cf noted contrast subjective cf demonstrated statistically significant relationship symbol digit modalities test sdmt r29 p05 hospital anxiety depression scale hads depression subscale r61 p 001 hads anxiety subscale r54 p 001 sleep quality r33 p02 additionally variables predicted subjective cf r2adj384 f 6 40 5783 p0002 particular anxiety significantly predicted subjective cf controlling depression information speed sleep qualityconclusion study demonstrated subjective cf significantly predicted anxiety strongly influenced information processing impairment depression addressing underlying affective factors anxiety depression may help alleviate perceived subjective cf among pwms thus improving function quality life studies larger sample size longitudinal follow may help define predictors objective cf,0.0
analysis status tendency ramp amp d input field rare diseases funded national natural science foundation china front public health 2021 oct 6 9729162 doi 103389 fpubh2021729162 ecollection 2021abstractbackground collection sorting rare disease projects funded national natural science foundation china understanding gained categories projects funded foundation field rare diseases types diseases categories disease systems regional distribution distribution supporting institutions dynamic changes followed analysis focuses influences relevant state policies will help improve rare diseaserelating policies state supporting key fields thus promoting healthy sustainable development field rare diseases method website inquiry projects funded national natural science foundation china retrieval made concerning projects funded foundation field rare diseases period 1986 2019 followed descriptive analysis fund input rare disease projects number projects temporal regional distribution analysis law dynamic changes result end 2019 57 rare diseases 678 related projects funded national natural science foundation china accumulated total funding 253 525 000 among categories projects mostfunded projects general 150 145 000 5922 followed youth foundation projects 53 719 000 2119 key projects 15 870 000 626 among categories disease systems funded disease system nervous system 93 186 000 3776 followed respiratory system 35 444 000 1398 funded diseases multiple sclerosis 34 870 000 1375 idiopathic pulmonary fibrosis 29 854 000 1178 retinitis pigmentosa 27 005 000 1065 funded regions east china 106 987 000 4220 north china 71 844 000 2834 least funded region northwest china 7 295 000 288 among supporting institutions funded institutions peking university 24 720 000 975 sun yatsen university 14 505 000 572 conclusion promulgation policies encouragement innovation accelerated approval procedures etc national natural science foundation china increasing funding rare diseases covering increasingly categories funded projects types diseases wider regions nonetheless support scientific research china still relatively weak therefore proposed healthy sustainable development course rare diseases promoted improvement relevant rare disease policies encouragement rd medicine rare diseases establishment special funds rare diseases acceleration fund circulation combination balanced development preferential funding key regions major diseasespmid34712637 pmcpmc8547256 doi103389 fpubh2021729162,0.0
spinal cord injury induces permanent reprogramming microglia diseaseassociated state contributes functional recovery microglia resident myeloid cells central nervous system recently singlecell rna sequencing enabled description diseaseassociated subtype microglia dam role neurodegeneration demyelination study use scrnaseq investigate temporal dynamics immune cells harvested epicenter traumatic spinal cord injury sci induced female mice find consequence sci baseline microglia undergo permanent transcriptional reprogramming previously uncharacterized subtype microglia striking similarities previously reported dam well distinct microglial state found development using microglia depletion model showed dam sci derived baseline microglia strongly enhance recovery hind limb locomotor function following injurysignificance statementalthough disease associated microglia subject strong research interest recent years eg jordo 2019 kerenshaul 2017 cellular origin role normal acute injury processes well understood work directly addresses origin role dam traumatic injury response use microglia depletion model prove dam sci indeed derived homeostatic microglia strongly enhance recovery thus work significantly expand knowledge immune response traumatic injury demonstrate applicability human injury via unique access injured human spinal cord tissue provide community comprehensive data set exploration,1.0
treatment patterns pediatric patients multiple sclerosis germanya nationwide claimbased analysis ther adv neurol disord 2021 oct 6 1417562864211048336 doi 101177 17562864211048336 ecollection 2021abstractbackground manifestation multiple sclerosis ms childhood adolescence occurs 35 ms cases however immunomodulatory symptomatic treatment options population group still limitedobjective aimed elucidate prescription frequency medications used pediatric patients multiple sclerosis pwms compared general population considering entire spectrum medications prescribedmethods based nationwide outpatient drug prescription data statutory health insurance shi physicians claims data 2018 conducted populationbased crosssectional study germany children adolescents aged 17 years n 11 381 939 diagnosed ms n 613 matched age sex health insurance sector control group n 6130 included prescription prevalence measured proportion ms patients 1 prescriptionresults 613 pediatric pwms median age 16 years 403 657 female 15 18 different active agents analyzed pwms significantly higher prescription prevalence control group fishers exact test p 0037 frequently prescribed drugs pwms ibuprofen 284 antiinflammatory drug cholecalciferol 230 vitamin d3 interferon beta1a 215 diseasemodifying drug dmd proportions dmd prescriptions antibiotic prescriptions higher among pwms aged 1517 years among 14 years dmd 434 vs 342 p 005 antibiotic 341 vs 248 p 0031 contrast younger pwms likely receive prescription antiinflammatory antirheumatic drugs 366 vs 265 p 002 conclusion study analyzing realworld medication data showed interferon beta antiinflammatory drugs vitamins play essential role treatment pediatric pwms future research evaluate longitudinal treatment patterns pediatric pwms paying particular attention time diagnosis time first dmd initiation therapy switchespmid34646362 pmcpmc8504210 doi101177 17562864211048336,0.0
early changes exo endocytosis eae mouse model multiple sclerosis correlate decreased synaptic ribbon size reduced ribbonassociated vesicle pools rod photoreceptor synapses int j mol sci 2021 oct 6 22 19 10789 doi 103390 ijms221910789abstractmultiple sclerosis ms inflammatory disease central nervous system finally leads demyelination demyelinating optic neuritis frequent symptom ms recent studies also revealed synapse dysfunctions ms patients ms mouse models previously reported alterations photoreceptor ribbon synapses experimental autoimmune encephalomyelitis eae mouse model ms present study found previously observed decreased imunosignals photoreceptor ribbons early eae resulted decrease synaptic ribbon size whereas number density ribbons photoreceptor synapses remained unchanged smaller photoreceptor ribbons associated fewer docked ribbonassociated vesicles functional level depolarizationevoked exocytosis monitored optical recording diminished even early day 7 eae induction moreover compensatory postdepolarization endocytosis decreased decreased postdepolarization endocytosis early eae correlated diminished synaptic enrichment dynamin3 contrast basal endocytosis photoreceptor synapses resting nondepolarized retinal slices increased early eae increased basal endocytosis correlated increased dephosphorylation dynamin1 thus multiple endocytic pathways photoreceptor synapse differentially affected early eae likely contribute observed synapse pathology early eaepmid34639129 doi103390 ijms221910789,1.0
covid19related allcause mortality risk among middleaged older adults across first epidemic wave sarscov2 infection populationbased cohort study southern catalonia spain marchjune 2020 background direct indirect covid19related mortality uncertain study investigated allcause covid19related deaths among middleaged older adults first wave covid19 pandemic period assessing mortality risks preexisting sociodemographic medical underlying conditionsmethodspopulationbased cohort study involving 79 083 individuals 50 yearsold tarragona southern catalonia spain baseline cohort characteristics age sex comorbidities medications vaccinations history established study start 01 03 2020 main outcomes covid19related deaths occurred among patients laboratoryconfirmed covid19 allcause deaths occurred among cohort members 01 03 202030 06 2020 mortality risks assessed cox regression analysesresultscohort members followed 1 356 358 personsweeks occurring 576 allcause deaths 124 covid19related deaths 124 deceased patients laboratoryconfirmed covid19 112 903 died due covid19 12 97 died covid19 likely due concomitant causes allcause mortality rate among cohort members across study period 425 deaths per 100 000 personsweek 228 among healthy unrelatedcovid19 subjects 2364 covid19excluded pcrnegative subjects 4937 covid19compatible pcrunperformed subjects 40091 covid19confirmed patients increasing age sex male nursinghome residence cancer neurologic cardiac liver disease receiving diuretics systemic corticosteroids protonpump inhibitors benzodiazepines associated increased risk allcause mortality conversely receiving reninangiotensin inhibitors statins associated reduced risk age years hazard ratio hr 108 95 confidence interval ci 106110 sex male hr 182 95 ci 124270 nursinghome residence hr 1256 95 ci 8071954 number preexisting comorbidities hr 114 95 ci 101129 significant predictors covid19related mortality none specific comorbidity emerged significantly associated increased risk multivariable analysis evaluating itconclusioncovid19related deaths represented 20 allcause mortality occurred among middleaged older adults first wave pandemic region considerable proportion around 10 covid19related deaths attributed concomitant causes theoretically covid19excluded subjects pcrnegative suffered tentimes greater allcause mortality healthy unrelatedcovid19 subjects points existence considerable number false negative results earlier pcr testing explain part global excess allcause mortality observed pandemic,0.0
vitro vivo investigation s1pr1 expression central nervous system using 3h cs1p1 11c cs1p1 acs chem neurosci 2021 sep 13 doi 101021 acschemneuro1c00492 online ahead printabstractsphingosine1phosphate receptor 1 s1pr1 ubiquitously expressed among tissues plays key roles many physiological cellular processes central nervous system cns s1pr1 expressed different types cells including neurons astrocytes oligodendrocyte precursor cells s1pr1 recognized novel therapeutic target multiple sclerosis diseases previously reported promising s1pr1specific radioligand 11c cs1p1 previously named 11c tz3321 clinical investigation human use current study performed detailed characterization 3h cs1p1 binding specificity s1pr1 cns using autoradiography immunohistochemistry human rat cns tissues data indicate 3h cs1p1 binds s1pr1 human frontal cortex tissue kd 398 nm bmax 1725 nm distribution 3h cs1p1 human rat cns tissues consistent distribution s1pr1 detected immunohistochemistry studies micropet studies 11c cs1p1 nonhuman primate nhp show standardized uptake value 24 nhp brain testretest variability 023 among six different nhps radiometabolite analysis plasma samples nhp rat well rat brain samples showed 11c cs1p1 stable vivo kinetic modeling studies using twocompartment tissue model showed positron emission tomography pet data fit model well overall study provides detailed characterization 3h cs1p1 binding s1pr1 cns combined micropet studies nhp brain data suggest 11c cs1p1 promising radioligand pet imaging s1pr1 cnspmid34516079 doi101021 acschemneuro1c00492,0.0
discriminative mobility characteristics neurotypical young middleaged older adults using wireless inertial sensors sensors basel 2021 oct 6 21 19 6644 doi 103390 s21196644abstractagerelated mobility research often highlights significant mobility differences comparing neurotypical young older adults neglecting report mobility outcomes middleaged adults moreover analyses regularly determine measures mobility can discriminate groups age brackets thus current study aimed provide comprehensive analysis commonly performed aspects mobility walking turning sittostand balance determine variables significantly different furthermore able discriminate neurotypical young adults yas middleaged adults maas older adults oas study recruited 20 yas 20 maas 20 oas participants came laboratory completed mobility testing wearing wireless inertial sensors mobility tests assessed included three distinct twominute walks 360 turns five times sittostands clinical balance test capturing 99 distinct mobility metrics various mobility tests assessed 360 turning measures demonstrated significance yas maas although capacity discriminate groups achieved gait turning measures variety mobility measures demonstrated significance maas oas furthermore discrimination achieved mobility test results indicate greater mobility differences maas oas although discrimination achievable group comparisonspmid34640963 doi103390 s21196644,0.0
mtor signaling regulates metabolic function oligodendrocyte precursor cells promotes efficient brain remyelination cuprizone model demyelinating diseases multiple sclerosis ms primary loss myelin subsequent neuronal degeneration throughout central nervous system cns impair patient functionality importance mechanistic target rapamycin mtor signaling developmental myelination known studies yet directly examined function mtor signaling specifically oligodendrocyte ol lineage remyelination conditionally deleted mtor adult oligodendrocyte precursor cells opcs using ng2creert male adult mice test function new ols responsible remyelination early remyelination cuprizoneinduced demyelination mice lacking mtor adult opcs unchanged ol numbers thinner myelin myelin thickness recovered latestage repair suggesting delay myelin production mtor deleted adult opcs surprisingly loss mtor opcs effect efficiency remyelination lysophosphatidylcholine lesions either spinal cord corpus callosum suggesting mtor signaling functions specifically pathway dysregulated cuprizone promote remyelination efficiency determined cuprizone inhibition mtor cooperatively compromise metabolic function primary rat ols undergoing differentiation taken together results support conclusion mtor signaling opcs required overcome metabolic dysfunction cuprizonedemyelinated adult brainsignificance statement impaired remyelination oligodendrocytes contributes progressive pathology multiple sclerosis critical identify mechanisms improving remyelination goal study examine mtor signaling remyelination provide evidence mtor signaling promotes efficient remyelination brain cuprizonemediated demyelination effect remyelination lysophosphatidylcholine demyelination spinal cord brain also present novel data revealing mtor inhibition cuprizone treatment additively affect metabolic profile differentiating oligodendrocytes supporting mechanism observed remyelination delay data suggest altered metabolic function may underly failure remyelination ms lesions mtor signaling may therapeutic potential promoting remyelination,1.0
broad spectrum posterior reversible encephalopathy syndrome case series clinical paraclinical characterisation histopathological findings background posterior reversible encephalopathy syndrome pres clinicalneuroradiologically defined potentially reversible limited data histopathological findings aimed describe clinical paraclinical features patients pres regard reversibilitymethodsthis retrospective case series encompasses 15 pres cases 1300 evaluated patients single german center january 1 2010 june 15 2020 pres established according diagnostic criteria proposed berlin pres study 2012 one cases studied subject brain autopsyresultsfrom 15 patients studied median age 53 years range 1773 11 female 67 presented epileptic seizures 40 suffered encephalopathy reduced consciousness 53 developed delirium 47 headache visual disturbances subcortical brain mri abnormalities related pres observed patients one patient developed spinal ischemia another guillainbarr syndrome addition pres hypertensive blood pressure main underlying trigger condition patients clinical symptoms mri changes reversible 42 even progressive 3 5 patients median time symptom onset diagnosis nonreversible cases 7 days range 013 median delay diagnosis reversible group 1 day range 03 cerebellar brain stem involvement status epilepticus frequently patients nonreversible disease course mortality due pres occurred 13 patients neuropathological examination brain 57yearold female patient revealed major leukencephalopathic changes fibrinoid necrosis endothelial cells fresh petechial hemorrhages accordance presconclusionsour case series demonstrates pres reversible 42 studied patients delay diagnosis seems contribute limited reversibility poor outcome,0.0
humoral response induced primeboost vaccination chadox1 ncov19 mrna bnt162b2 vaccines teriflunomidetreated multiple sclerosis patient vaccines basel 2021 oct 6 9 10 1140 doi 103390 vaccines9101140abstractpatients multiple sclerosis ms treated drugs may impact immune responses sarscov2 vaccination evaluation primeboost heterologous vaccination regimens including first administration viral vectorbased vaccine second one mrnabased vaccine patients yet completed present antispike protein s humoral response including neutralizing antibody response 54yearold ms patient treated teriflunomide past 2 years received heterologous chadox1 ncov19 bnt162b2 vaccination regimen results showed strong antis igg response good neutralizing antibody response results show teriflunomide prevent development satisfactory humoral response ms patient vaccination chadox1 ncov19 bnt162b2 primeboost protocolpmid34696248 doi103390 vaccines9101140,0.0
teriflunomide treatment multiple sclerosis selectively modulates cd8 memory t cells front immunol 2021 oct 5 12730342 doi 103389 fimmu2021730342 ecollection 2021abstractbackground objectives inhibition de novo pyrimidine synthesis proliferating t b lymphocytes teriflunomide pharmacological inhibitor dihydroorotate dehydrogenase dhodh shown effective therapy treat patients ms placebocontrolled phase 3 trials nevertheless underlying mechanism contributing efficacy dhodh inhibition partially elucidated aimed determine impact teriflunomide immune compartment longitudinal highdimensional followup patients relapseremitting ms rrms treated teriflunomidemethods highdimensional spectral flow cytometry used analyze phenotype function innate adaptive immune system patients rrms 12 months teriflunomide treatment addition assessed impact teriflunomide migration memory cd8 t cells patients rrms defined patient immune metabolic profilesresults found 12 months treatment teriflunomide patients rrms affect b cell cd4 t cell compartments including regulatory treg follicular helper tfh cell helper th cell subsets contrast observed specific impact teriflunomide cd8 t cell compartment characterized decreased homeostatic proliferation reduced production tnf ifn furthermore showed dhodh inhibition also negative impact migratory velocity memory cd8 t cells patients rrms finally showed susceptibility memory cd8 t cells dhodh inhibition related impaired metabolismdiscussion overall findings demonstrate clinical efficacy teriflunomide results partially specific susceptibility memory cd8 t cells dhodh inhibition patients rrms strengthens active roles t cells pathophysiological process mspmid34721394 pmcpmc8552527 doi103389 fimmu2021730342,0.0
nuclear ubiquitin ligase adaptor spop conserved regulator c9orf72 dipeptide toxicity proc natl acad sci u s 2021 oct 5 118 40 e2104664118 doi 101073 pnas2104664118 epub 2021 sep 30abstracta hexanucleotide repeat expansion c9orf72 gene common cause inherited amyotrophic lateral sclerosis als frontotemporal dementia ftd unconventional translation c9orf72 repeat produces dipeptide repeat proteins dprs previously showed dprs pr50 gr50 highly toxic expressed caenorhabditis elegans toxicity depends nuclear localization dpr unbiased genomewide rna interference rnai screen suppressors pr50 toxicity identified 12 genes consistently suppressed either developmental arrest paralysis phenotype evoked pr50 expression genes vertebrate homologs 7 12 contain predicted nuclear localization signals one genes spop1 c elegans homolog spop nuclear localized e3 ubiquitin ligase adaptor found metazoans spop also required gr50 toxicity functions genetic pathway includes cul3 canonical e3 ligase partner spop genetic pharmacological inhibition spop mammalian primary spinal cord motor neurons suppressed dpr toxicity without affecting dpr expression levels finally find knockdown bromodomain proteins c elegans mammalian neurons known spop ubiquitination targets suppresses protective effect spop inhibition together data suggest model spop promotes dprdependent ubiquitination degradation brd proteins speculate pharmacological manipulation pathway currently underway multiple cancer subtypes also represent entry point therapeutic intervention treat c9orf72 ftd alspmid34593637 doi101073 pnas2104664118,0.0
hiv encephalopathy mimicking acute demyelinating processes cureus 2021 oct 5 13 10 e18494 doi 107759 cureus18494 ecollection 2021 octabstracthuman immunodeficiency virus hiv encephalopathy lies severe spectrum hivassociated neurological disorder hand ranges asymptomatic condition minor neurological features severe dementia cerebrospinal fluid csf analysis helps rule presence opportunistic infections neuroimaging helps establish diagnosis report case 39yearold african american female presented signs symptoms suggestive acute multiple sclerosis ms flares setting advanced acute immunodeficiency syndrome aids encephalopathy presented bilateral lower extremity muscle weakness pain apparent cognitive decline notable laboratory findings included leukopenia normal neutrophils positive serology hiv1 mri showed mild postcontrast enhancement suggestive demyelinating disease favoring ms progressive multifocal leukoencephalopathy pml cerebrospinal fluid analysis significant positive oligoclonal bands negative serology started antiretroviral therapy art aids holding steroids due possibility worsening aids treatment hiv showed immunologic functional status improvement hiv encephalopathy must diagnosed ruling similar presenting neurological illnesses tactful patient managementpmid34754655 pmcpmc8569688 doi107759 cureus18494,1.0
characterizing 1year development cervical cord atrophy across different ms phenotypes voxelwise multicentre analysis abstractbackgroundspatiotemporal evolution cord atrophy multiple sclerosis ms investigated yetobjectiveto evaluate voxelwise distribution 1year changes cervical cord atrophy multicentre ms cohortmethodsbaseline 1year 3d t1weighted cervical cord scans clinical evaluations 54 healthy controls hc 113 ms patients 14 clinically isolated syndromes cis 77 relapsingremitting rr 22 progressive p used investigate voxelwise cord volume loss patients versus hc 1year volume changes clinical correlations spm12 resultsms patients exhibited baseline cord atrophy versus hc anterior posterior lateral c1 c2 c4c6 p 005 corrected cis patients showed baseline volume increase c4 versus hc p 0001 uncorrected rrms exhibited posterior lateral c1 c2 atrophy versus cis pms showed widespread cord atrophy versus rrms p 005 corrected 1 year 13 patients clinically worsened cord atrophy progressed ms driven rrms posterior lateral c2 c3c6 p 005 corrected cis patients showed volume changes pms showed circumscribed atrophy progression baseline cord atrophy posterior lateral c1 c2 c3c6 correlated concomitant 1year disability r 040 062 p 005 corrected conclusionsvoxelwise analysis characterized spinal cord neurodegeneration 1 year across ms phenotypes helped explain baseline 1year disability,0.0
molecular mechanisms cordycepin emphasizing potential neuroinflammation update eur j pharmacol 2021 jul 20174364 doi 101016 jejphar2021174364 online ahead printabstractrecent research emphasizes central role neuroinflammation complex neurological disorders alzheimers disease parkinsons disease depression multiple sclerosis traumatic brain injury multiple pathological variables identical molecular mechanisms implicated development cns inflammatory diseases therefore one crucial tasks management cns disorders alleviation neuroinflammation however many drawbacks new pharmacological drugs used management cns disorders including medication side effects treatment complications growing inclination towards bioactive constituents natural origin unearth potential remedies cordycepin adenosine analogue one bioactive constituent multiple actions viz anticancer antiinflammatory hepatoprotective antidepressant antialzheimers antiparkinsonian immunomodulatory effects along promotion remyelination review highlights converging neuroinflammatory targets cordycepin alzheimers disease parkinsons disease depression substantiate antineuroinflammatory property cordycepin acts downregulation adenosine a2 receptor inhibition microglial activation subsequent inhibition several neuroinflammatory markers nfb nlrp3 inflammasome il1 inos cox2 tnf hmgb1 cordycepin mitigates lpsmediated tolllike receptor activation activating adenosine receptor a1 thereby improving antioxidant enzymes superoxide dismutase glutathione peroxidase levels pieces evidence point probable antineuroinflammatory mechanisms cordycepin facilitate development new remedies neuroinflammationassociated cns disorderspmid34297967 doi101016 jejphar2021174364,1.0
parp1mediated parylation activity essential oligodendroglial differentiation cns myelination cell rep 2021 oct 5 37 1 109695 doi 101016 jcelrep2021109695abstractthe function poly adpribosyl polymerase 1 parp1 myelination remyelination central nervous system cns remains enigmatic report parp1 intrinsic driver oligodendroglial development myelination genetic parp1 depletion impairs differentiation oligodendrocyte progenitor cells opcs oligodendrocytes impedes cns myelination mechanistically parp1mediated parylation activity necessary also sufficient opc differentiation molecular level identify rnabinding protein myef2 parylated target controls opc differentiation parylationmodulated derepression myelin protein expression furthermore parp1s enzymatic activity necessary oligodendrocyte myelin regeneration demyelination together findings suggest parp1mediated parylation activity may potential therapeutic target promoting opc differentiation remyelination neurological disorders characterized arrested opc differentiation remyelination failure multiple sclerosispmid34610310 doi101016 jcelrep2021109695,1.0
astrocytic yap prevents demyelination promoting expression cholesterol synthesis genes experimental autoimmune encephalomyelitis cell death dis 2021 oct 5 12 10 907 doi 101038 s41419021042038abstractcholesterols main components myelin mainly synthesized astrocytes transported oligodendrocytes neurons adult brain reported hippo yesassociated protein yap pathways involved cholesterol synthesis liver however remains unknown whether yap signaling can prevent demyelination promoting cholesterol synthesis experimental autoimmune encephalomyelitis eae commonly used animal model multiple sclerosis characterized neuroinflammation demyelination found yap upregulated activated astrocytes spinal cords eae mice suppression hippo pathway yap deletion astrocytes aggravated eae earlier onset severer inflammatory infiltration demyelination loss neurons furthermore found neuroinflammation aggravated proliferation astrocytes decreased yapgfapcko eae mice mechanically rnaseq revealed expression cholesterolsynthesis pathway genes hmgcs1 decreased yap astrocytes qpcr western blot immunostaining confirmed significant reduction hmgcs1 spinal cord astrocytes yapgfapcko eae mice interestingly upregulation cholesterolsynthesis pathways diarylpropionitrile dpn erligand upregulate expression hmgcs1 treatment partially rescued demyelination deficits yapgfapcko eae mice finally activation yap xmump1 treatment promoted expression hmgcs1 astrocytes partially rescued demyelination inflammatory infiltration deficits eae mice findings identify unrecognized functions astrocytic yap prevention demyelination promoting cholesterol synthesis eae reveal novel pathway yap hmgcs1 cholesterol synthesis eae pathologypmid34611127 doi101038 s41419021042038,1.0
effects lipoic acid ischemiareperfusion injury oxid med cell longev 2021 oct 5 20215093216 doi 101155 2021 5093216 ecollection 2021abstractischemiareperfusion r injury often occurred pathologies surgeries r injury harmed physiological functions corresponding organ tissue also induced multiple tissue organ dysfunctions even distant locations although reperfusion blood attenuated r injury certain degree risk secondary damages difficult controlled even caused failures tissues organs lipoic acid la endogenous active substance functional agent food owns better safety effects body eg enhancing antioxidant activity improving cognition dementia controlling weight preventing multiple sclerosis diabetes complication cancer literature searching conducted pubmed embase cochrane library web science scopus inception 20 may 2021 showed endogenous la exhausted process r aggravated r injury thus supplements la timely especially pretreatments may prospective way prevent r injury recently studies demonstrated la supplements significantly attenuated r injuries many organs though clinic investigations short present hence urgent summarize progresses effects la different r organs well potential mechanisms enlighten investigations prepare clinic applications futurepmid34650663 pmcpmc8510805 doi101155 2021 5093216,0.0
choroid plexus volumetrics brain inflammation multiple sclerosis proc natl acad sci u s 2021 oct 5 118 40 e2115221118 doi 101073 pnas2115221118no abstractpmid34583997 doi101073 pnas2115221118,0.0
rapid sustained bcell depletion subcutaneous ofatumumab relapsing multiple sclerosis aplios randomized phase2 study abstractbackgroundofatumumab first fully human anticd20 monoclonal antibody approved several countries relapsing multiple sclerosis rms objectiveto demonstrate bioequivalence ofatumumab administered autoinjector versus prefilled syringe pfs explore effect ofatumumab bcell depletionmethodsaplios nct03560739 12week openlabel parallelgroup phase2 study patients rms receiving subcutaneous ofatumumab 20 mg every 4 weeks q4w week 4 initial doses days 1 7 14 patients randomized 101011 autoinjector pfs abdomen autoinjector pfs thigh respectively bioequivalence determined area curve auc maximum plasma concentration cmax weeks 812 bcell depletion safety tolerability assessedresultsa total 256 patients contributed bioequivalence analyses autoinjectorabdomen n 128 pfsabdomen n 128 abdominal ofatumumab pharmacokinetic exposure bioequivalent autoinjector pfs geometric mean auc 4877 vs 4741 h g ml ratio 103 cmax 1409 vs 1409 g ml ratio 100 bcell counts median cells l depleted rapidly groups 2140 baseline 20 day 14 ofatumumab well toleratedconclusionofatumumab 20 mg q4w selfadministered subcutaneously via autoinjector bioequivalent pfs administration provides rapid bcell depletion,0.0
ctbased morphological comparison glenoid inclination version angles mineralisation distribution human body donors background optimal prosthetic anchoring omarthritis surgery differentiated knowledge mineralisation distribution glenoid important however database mineralisation diseased joints potential relations glenoid angles limitedmethodsshoulder specimens ten female nine male body donors average age 815 years investigated using 3dctmultiplanar reconstruction glenoid inclination retroversion angles measured osteoarthritis signs graded computed tomographyosteoabsorptiometry ctoam established method determine subchondral bone plate mineralisation demonstrated serve marker longterm loading history joints based mineralisation distribution mappings healthy shoulder specimens physiological different ctoam patterns compared glenoid anglesresultsosteoarthritis grades 0i 526 3dctscans grades iiiii 343 grade iv 132 females twice frequently 45 higher grades iii iv males 22 iii average inclination angle 84 glenoids inclination 10 mineralisation predominantly centrally distributed tended shift cranially inclination raised 10 average retroversion angle 52 dorsally enhanced mineralisation distribution found glenoids versions 159 + 17 predominantly centrally distributed mineralisation accompanied narrower range retroversion angles 10 04conclusionsthis study one first combine ctbased analyses glenoid angles mineralisation distribution elderly population data set limited 19 individuals however indicates superior inclination 0 1015 dorsal version ranging 9 3 may predominantly associated anterior central mineralisation patterns previously classified physiological shoulder joint current basic research findings may serve basic data set future studies addressing glenoid geometry treatment planning omarthritis,0.0
diseaserelated knowledge measurement instruments people affected multiple sclerosis protocol systematic psychometric review bmj open 2021 oct 5 11 10 e049580 doi 101136 bmjopen2021049580abstractintroduction diseaserelated knowledge key component shared decision making relevant outcome measure effectiveness information provision interventions however systematic psychometric reviews found assess measurement instruments aimed evaluating diseaserelated knowledge people affected multiple sclerosis review aims systematically assess quality measurement properties available diseaserelated knowledge measurement instruments people affected multiple sclerosismethods analysis systematic psychometric review will carried accordance guidelines proposed international consensusbased standards selection health measurement instruments cosmin initiative studies meet following criteria will selected 1 whose aim measure diseaserelated knowledge 2 whose study populations affected multiple sclerosis 3 whose aims develop measurement instruments evaluate one measurement properties information sources will medline via pubmed cinahl psycinfo opengrey methodological quality will assessed using cosmin risk bias checklist available evidence will synthesised graded using modified grading recommendations assessment development evaluation approachethics dissemination systematic review ethics approval needed study findings will shared multiple sclerosis patient support groups reports funders results will submitted peerreviewed journal will presented national international conferencesprospero registration number crd42019125417pmid34610936 doi101136 bmjopen2021049580,0.0
fungal microbiome multiple sclerosis notsonew kid block human hosts commensal gut microbes symbiotic relationship hosts providing space nutrients microbes microbes supporting numerous physiological processes host including digestion food preventing pathogen colonization immune system modulation 1 thus surprising perturbations homeostasis linked number diseases 1 last two decades nonculturebased sequencing techniques afforded better understanding human microbiome health disease including multiple sclerosis ms several groups including ours shown patients ms gut dysbiosis specific bacteria either enriched depleted 2 however studies analyzed bacteria even though microbiome also consists fungi viruses article shah et al 3 profile fungal microbiome mycobiome patients ms pwms show patients distinct mycobiome compared healthy control hc participants study shah et al another preprint yadav et al showing fungal dysbiosis pwms 4 begin highlight importance mycobiome msshat et al compared mycobiomes 25 pwms 22 hcs showed mycobiome pwms higher fungal richness hcs mycobiome composition remaining mostly stable sixmonths 3 mycobiome pwms enriched certain fungi saccharomyces aspergillus interestingly diseasemodifying therapies including dimethyl fumarate possesses antifungal properties alter mycobiome composition authors also associated mycobiome profiles different microbiome compositions classifying mycobiome profiles two fungal clusters ie mycotypes mycotype 1 dominated saccharomyces whereas mycotype 2 greater diversity presence penicillium malassezia mucor besides saccharomyces positive correlation saccharomyces circulating basophil levels increased levels effector memory cd4+ t cells participants mycotype 2 cluster collectively results demonstrate mycobiota altered context ms likely implications disease progression severity particularly considering previous report showing distinct mycobiome signature patients diseases inflammatory bowel disease cancers atherosclerosis diabetes obesity alcoholic liver disease 5 6 view related content articlelike bacteria fungi also proposed play important symbiotic role maintaining immune homeostasis mucosal surfaces regulating innate adaptive immunity recognition fungi innate immune receptors dectin1 dectin2 ctype lectin receptors macrophageinducible ca2+dependent lectin receptor help finetune immune responses gut 6 additionally fungi specifically candida malassezia potent inducers systemic th17 response promote expansion neutrophil population 5 6 7 importance mycobiome t cell activation granulocytes expansion highlighted two recent studies show mycobiome enriched offspring wild mice received embryos laboratory mice laboratory mice reintroduced wild 8 9 laboratory mice differ human immune system reduced numbers activated t cells polymorphonuclear lymphocytes blood studies suggest lack complex commensal fungi mice might responsible differences immune parametersthe study discussed limited small sample size classification fungi low resolution absence validation cohort patients candida saccharomyces two abundant fungi human mycobiome significantly reduced abundance candida observed 3 surprising several human studies shown relatively higher abundance candida healthy participants 10 patients disease inflammatory bowel disease atherosclerosis type 2 diabetes mellitus 5 6 also observed higher candida levels pwms compared hc using markerbased fungal classification 4 lower candida levels current study may due geographic location lifestyles dietary habits participants bioinformatics pipeline used saccharomyces associated healthy mycobiome certain diseases suggesting either strainspecific role saccharomyces promoting disease overall composition mycobiome bacterial microbiome affects diseaseprotective promoting properties correlating abundance saccharomyces candida components microbiome context ms will important next step beginning uncover fungi might protect promotes diseasein conclusion study provides first evidence fungal component microbiome disrupted pwms paves way future work characterizing mycobiome context disease using shotgun metagenomic sequencing larger sample sizes combined mechanistic studies will help understanding precise role fungi pathobiology ms,0.0
predictors adherence persistence diseasemodifying therapies multiple sclerosis ther adv neurol disord 2021 oct 5 1417562864211031099 doi 101177 17562864211031099 ecollection 2021abstractbackground aims multiple sclerosis ms nonadherence nonpersistence related suboptimal response treatment including disease relapses need expensive healthcare aim study identify predictors related adherence disease modifying therapies dmts cohort argentinian ms patientsmethods conducted crosssectional study national medical care program argentina ms patients least one claim dmt 1 january 2017 1 october 2017 identified telephone survey performed assess clinical demographic factors medication possession ratio mpr used estimate adherence mpr 80 defined nonadherence associations studied using logistic regression modelresults database included 648 ms patients total 360 patients 60 females mean age 553 years accepted participate 308 855 patients receiving dmt time survey 198 637 receiving injectable therapies optimal adherence 477 adherence associated oral medication odds ratio 183 95 confidence interval ci 113300 p 0014 factor related oral drugs higher educational level 286 95ci 141581 p 0004 conclusion realworld study showed better adherence persistence treatment oral therapies ms patients argentinapmid34630632 pmcpmc8495537 doi101177 17562864211031099,0.0
uncommon cause acute transverse myelitis following acinetobacter baumanniiassociated uti responded intravenous pulse methylprednisolone alone cureus 2021 oct 5 13 10 e18509 doi 107759 cureus18509 ecollection 2021 octabstractacute transverse myelitis atm noncompressive localized inflammation involving one levels spinal cord due various etiologies characterized motor weakness sensory impairments autonomic dysfunction can idiopathic primary secondary due infection autoimmune disorder connective tissue disorder uncommonly vaccination came limelight ongoing massive vaccine drive coronavirus disease 2019 covid19 report case 21yearsold male presented gradually progressive weakness lower limbs following urinary tract infection uti history similar illness family improved high dose methylprednisolone antibiotic therapy followed physical rehabilitation diagnosis long segment atm possibly following uti suggested ruling secondary causes confirmed magnetic resonance imaging mri spinal cord asymmetric symptoms signs small lesions involving two vertebral segments peripheral lesion presence lhermittes sign relapsingremitting course distinguish atm debilitating disorder multiple sclerosis ms patients family history infection like uti can precipitate atm well uti may develop along neurogenic lower urinary tract dysfunction nlutd even recovery motor sensory impairment patients acute transverse myelitis need regular follow particularly subacute presentation positive family history rule relapse development multiple sclerosis common etiologies like uti may precipitate uncommon disorders like atmpmid34754669 pmcpmc8569673 doi107759 cureus18509,0.0
impact vitamin d supplementation multiple sclerosis cureus 2021 oct 5 13 10 e18487 doi 107759 cureus18487 ecollection 2021 octabstractmultiple sclerosis ms autoimmune disease affecting large number people every year exact causal factor disease unclear commonly affects middleaged women known triggers like stress childbirth infections poor diet lack sleep etc many epidemiological studies indicated various genetic abnormalities also critical drivers onset ms major risk factors ms identified include hypovitaminosis d environmental protective factors include allele hla drb1 1501 obesity epsteinbarr virus infection sexual hormones smoking article explores correlation deficiency vitamin d onset progression ms study uses systematic review methodology researching reviewing scholarly articles exploring topic conducted online searches literature google scholar pubmed using keywords vitamin d deficiency multiple sclerosis accessed relevant secondary literature sources review variables study included vitamin d insufficiency dependent variable ms independent variable causal variables included environmental genetic protective factors hypothesized indeed correlation vitamin d deficiency ms findings review indicate strong correlation insufficiency vitamin d onset progression ms results essential devising interventions accomplish primary secondary prevention ms well integrating vitamin d supplementation current treatment protocols mspmid34754649 pmcpmc8567111 doi107759 cureus18487,0.0
isolated cognitive syndrome prodromal presentation multiple sclerosis read great interest recently published article simonsen et al simonsen et al 2021 premorbid school achievement patients develop multiple sclerosis ms later design although similar article published team 2015 observe findings,0.0
expression correlational patterns among neuroinflammatory neuropeptide neuroendocrine molecules cerebrospinal fluid cerebral palsy background underlying pathogenesis cerebral palsy cp remains poorly understood possibility early inflammatory response acute insult increasing interest patterns inflammatory related biomarkers emerging potential early diagnostic markers understanding etiologic diversity cp presence investigated plasma umbilical cord blood cerebrospinal fluid csf methodsa clinical cp sample recruited using singletime point crosssectional design collect csf pointofcare standardofcare surgical procedure intrathecal pump implant patient demographic clinical characteristics sourced medical chart auditresultssignificant p 0001 associations found among neuroinflammatory neuroendocrine nociceptive analytes association patterns varying birth status term preterm extremely preterm birthgroup correlations compared directly significant difference preterm extremely preterm birth subgroups correlation tumour necrosis factor alpha tnf substance pconclusionthis investigation shows csf can used study proteins cp patients differences intercorrelational patterns among analytes varying birth status underscores importance considering birth status relation possible mechanistic differences indicated biomarker signatures future work oriented toward prognostic predictive validity continue parse heterogeneity cps presentation pathophysiology response treatment,0.0
altered adipokine levels associated dimethyl fumarate treatment multiple sclerosis patients abstractbackground obesity linked increased risk multiple sclerosis ms worsening disease severity recent experimental clinical data indicates adipokines involved regulating immune response serve cross talk immune neural system dimethyl fumarate dmf oral ms medication unknown mechanism action upregulates nuclear factor e2related factor 2 nrf2 pathway pathway adipocyte differentiation determine possible relationship treatment dimethyl fumarate serum adipokine profiles treatment response patients ms conducted observational cohort study measured serum adipokine vitamin d levels treatment dmf examined association treatment responsemethods identified patients enrolled comprehensive longitudinal investigation multiple sclerosis brigham womennulls hospital climb study treated dimethyl fumarate available serum samples longitudinal pretreatment ontreatment samples available 23 patients crosssectional ontreatment samples available 91 patients classified dmf responders nonresponders based radiologic clinical relapse activity disability progression measured serum leptin adiponectin resistin ghrelin fatty acid binding protein4 fabp4 and5 fabp5 vitamins d2 d3 statistical analysis performed paired ttests wilcoxon signedrank mannwhitney u testsresults treatment dmf serum adiponectin levels significantly increased whereas fabp4 levels significantly decreased compared baseline levels without statistically significant change patientsnull bmi ghrelin levels insignificantly lower posttreatment fabp4 levels significantly higher dmf responders compared nonresponders effect sexspecific higher fabp4 levels associated treatment response males femalesconclusion dmf treatment associated significant changes serum adipokine levels primarily adiponectin fabp4 sex may affect association fabp4 treatment response,0.0
prescribing disease modifying agents older adults multiple sclerosis abstractbackgroundthe use diseasemodifying agents dma treat multiple sclerosis ms older adults debated disease activity decreases aging however limited data exist regarding prescribing patterns dma among older adults msobjectiveto examine prescribing patterns dmas factors associated dma prescribing practices among older adults ms using electronic medical records emr datamethodsa retrospective longitudinal cohort study conducted using trinetx federated emr network us data 20162019 study included older adults 60 years ms diagnosis least one prescription record study period patients dma prescriptions identified classified injectable oral infusion users based last dma prescription multivariable logistic regression model used evaluate factors associated prescribing dmas multinomial logistic regression model also used determine factors associated prescribing particular dosage form dmaresultsthe study cohort consisted 12 922 older adults ms 2 455 1899 receiving dma prescriptions frequency prescribed dmas injectables 1046 followed orals 606 infusions 240 multivariable logistic regression revealed older adults 6064 years adjusted odds ratio aor 238 6569 years aor160 higher odds receiving dma compared older adults 70 years african americans aor171 higher odds receiving dma prescriptions compared caucasians presence symptoms pain fatigue speech walking difficulty use symptomatic medication antifatigue medication bladder dysfunction medication antispasmodics antidepressants relapse medication higher odds prescribed dma multinomial logistic regression found patients 6064 years age higher odds prescribed infusion aor 95 confidence interval ci 206 135315 oral 6569 years aor160 124207 injectable dma compared older adults aged 70 years older males aor168 95 ci 123230 associated increased odds prescribed infusion dma injectable dma compared females presence comorbidities coagulopathy peripheral vascular disorders lower odds prescribed oral dma injectable dma patients cerebellar symptoms increased likelihood prescribed infusion dma injectable dma patients using drugs treating relapses higher odds prescribed infusion dma injectable dma terms healthcare utilization older adults outpatient visits aor175 95 ci 126243 higher odds prescribed infusion dma injectable dma older adults inpatient visits aor032 95 ci 011096 lower odds prescribed infusion dma injectable dmaconclusionnearly one five older adults ms prescribed dmas majority receiving injectable dmas several demographic clinical factors associated prescribing dmas study fills data gap regarding utilization dmas older adults ms,0.0
assessing differential sensitivities wavecaipi vista myelin water fraction magnetization transfer saturation efficiently quantifying tissue damage ms abstractbackground wavecaipi visualization short transverse relaxation time component vista recently developed shortt1sensitized mri method fast quantification myelin water fraction mwf human brain represents promising technique evaluation subtle early signals demyelination cerebral white matter multiple sclerosis ms patients currently however studies exist robustly assess utility vista mwf measures myelin compared conventional mri measures myelin brain ms patients moreover previous studies evaluating sensitivity vista mwf noninvasive detection subtle tissue damage normalappearing white matter nawm white matter lesions ms patients result central purpose study systematically evaluate relationship myelin sensitivity t1based vista mwf mapping generally recognized metric magnetization transfer saturation mtsat healthy control ms brain white mattermethods vista mwf mtsat values evaluated automaticallyclassified normal appearing white matter nawm white matter wm lesion tissue cortical gray matter deep gray matter 29 ms patients 10 healthy controls using 3t mri mwf mt sat also assessed tractspecific manner using johns hopkins university wm atlas mriderived measures cerebral myelin content uniquely compared employing nonnormal distributionspecific measures median interquartile range skewness separate analyses variance applied test tissuespecific differences mtsat vista mwf distribution metrics nonparametric tests utilized appropriate tests corrected multiple comparisons using false discovery rate method level 005results differences whole nawm ms tissue damage detected higher effect size using vista mwf q00008 2034 compared mtsat q002 2024 also observed possible measure wm pathology vistaderived nawm mwf voxel distributions ms subjects consistently skewed towards lower mwf values mtsat voxel distributions showed reduced skewness values identified tractspecific reductions mean vista mwf ms patients compared controls observed mtsat however mtsat q141021 2 088 displayed higher effect sizes differentiating nawm ms lesion tissue using regression analysis group level identified linear relationship mtsat vista mwf nawm r2046 p78104 lesions r2030 p0004 tissue types combined r2071 p841045 linear relationship also observed wm tracts investigated vista mwf nawm ms patients correlated disease duration p002 r2027 wm lesion volume p0002 r2034 conclusion vista mwf mtsat metrics exhibit differential sensitivities tissue damage ms white matter can collected combination provide efficient comprehensive measure myelin water macromolecular pool proton signals complementary measures may offer sensitive noninvasive biopsy early precursor signals nawm occur prior lesion formation may also aid monitoring efficacy remyelination therapies,1.0
retinal microvascular neuronal function patients multiple sclerosis 2year followup abstractobjective determine longitudinal changes retinal microstructure microvasculature microcirculation axonal neuronal functions patients relapsingremitting multiple sclerosis rrms time course two yearsmethods total 30 patients 60 eyes rrms followed period 27 6 months evaluated battery clinical tests including low contrast letter acuity lcla intraretinal layer thicknesses optical coherence tomography oct ganglion cell function steadystate pattern electroretinography perg axonal function polarizationsensitive oct volumetric vessel density vvd oct angiography retinal tissue perfusion rtp retinal function imagerresults axonal function measured retinal nerve fiber layer birefringence temporal quadrant vessel density deep vascular plexus significantly decreased 2year followup p 005 subgroup analyses showed increased retinal blood flow volume occurred patients evidence disease activity neda stable improved visual function p 005 significant difference expanded disability state scale lcla rtp vvd perg measures two visits p 005 conclusion best knowledge first 2year prospective comprehensive study detailed assessment retinal microstructure neuronal functions patients rrms recovery retinal microcirculation occurred patients neda stable improved visual function suggesting measurements potential imaging biomarkers monitoring disease progression,0.0
intranasal administration undifferentiated oligodendrocyte lineage cells potential approach deliver oligodendrocyte precursor cells brain int j mol sci 2021 oct 4 22 19 10738 doi 103390 ijms221910738abstractoligodendrocyte precursor cell opc migration mechanism involved remyelination cells migrate niches adult cns however age disease reduce pool opcs result remyelination capacity cns decreases time several experimental studies introduced opcs brain via direct injection intrathecal administration study used noseto brain pathway deliver oligodendrocyte lineage cells human oligodendroglioma hog cells behave similarly opcs vitro end administered gfplabelled hog cells intranasally experimental animals subsequently euthanised 30 60 days results show intranasal route viable route cns hog cells administered intranasally migrate preferentially niches opcs clusters created embryonic development adult life study provides evidence albeit limited hog cells either form clusters adhere clusters opcs brains experimental animalspmid34639079 doi103390 ijms221910738,1.0
systemic intrathecal baclofen produce bladder antinociception rats background baclofen clinically available gabab receptor agonist produces nonopioid analgesia multiple models pain tested effects bladder nociceptionmethodsa series experiments examined effects systemic spinally administered baclofen bladder nociception female anesthetized rats models bladder nociception included employed neonatal adult bladder inflammation produce bladder hypersensitivityresultscumulative intraperitoneal dosing 18 mg kg ip cumulative intrathecal dosing 10160 ng baclofen led dosedependent inhibition visceromotor responses vmrs urinary bladder distension ubd tested models differences magnitude analgesic effects baclofen function inflammation versus inflammation treatments hemodynamic pressor responses ubd similarly inhibited baclofen well ubdevoked excitatory responses spinal dorsal horn neurons gabab receptor antagonist cgp 35 348 antagonized antinociceptive effects baclofen vmrs tested models affect magnitude vmrs suggesting tonic gabab activity present preparation tolerance seven day continuous infusion baclofen observedconclusionsthese data provide support clinical trial baclofen nonopioid treatment human bladder pain,0.0
t cellintrinsic function nfb relb experimental autoimmune encephalomyelitis sci rep 2021 oct 4 11 1 19674 doi 101038 s4159802199134xabstractnfkappab nfb family transcription factors pleiotropic functions immune responses alternative nfb pathway leads activation relb nfb2 previously associated activation function t cells though exact contribution nfb subunits remains unclear using mice carrying conditional ablation relb t cells evaluated role development conventional cd4+ t tconv cells function autoimmune diseases relb largely dispensable tconv cell homeostasis activation proliferation polarization toward different flavors thelper cells vitro moreover ablation relb impact capacity tconv cells induce autoimmune colitis conversely clinical severity experimental autoimmune encephalomyelitis eae mouse model multiple sclerosis ms significantly reduced mice relbdeficient t cells associated impaired expression granulocytemacrophage colonystimulating factor gmcsf specifically central nervous system data reveal discrete role relb pathogenic function tconv cells eae highlight transcription factor putative therapeutic target mspmid34608221 doi101038 s4159802199134x,0.0
conserved spinal cord bioenergetics experimental autoimmune encephalomyelitis c57bl6 mice measured using phosphorescence oxygen analyzer heliyon 2021 oct 4 7 10 e08111 doi 101016 jheliyon2021e08111 ecollection 2021 octabstractbackground previously reported spinal cord respiration cellular mitochondrial oxygen consumption atp content conserved studied model experimental autoimmune encephalomyelitis eae foreseeing recovery diseased rats exemplary lesion multiple sclerosis used measure spinal cord bioenergetics c57bl6 mice hypothesis despite wellknown focal axonal mitochondrial pathology bioenergetics cns reasonably preserved diseasemethods eae induced immunodominant myelin oligodendrocyte glycoprotein epitope complete freunds adjuvant appended injections pertussis toxin low highdose encephalitogen administered base tail hindflank investigated control mice received incomplete adjuvant tail oxygen measurements based quenching phosphorescence pd ii mesotetra sulfophenyl tetrabenzoporphyrin molecular oxygen cellular atp measured using luciferin luciferase systemresults kinetics spinal cord oxygen consumption zeroorder linear time inhibited cyanide confirming oxygen reduced cytochrome oxidase rate respiration m o2min1mg1 measured days 1328 control mice mean sd 0086 0024 n 8 immunized mice 0079 0020 n 15 p 0265 mannwhitney test consistently cellular atp mol mg1 dry pellet weight measured days 1328 control mice 0068 0079 n 11 immunized mice 0063 0061 n 24 p 0887 mannwhitney u test conclusions vitro measurements spinal cord bioenergetics show conservation mitochondrial function mice eae results suggest previously documented reduced mitochondrial electrochemical potential disease alterable likely reflects adverse events neuroinflammationpmid34693048 pmcpmc8511844 doi101016 jheliyon2021e08111,1.0
relationship plantar sensation muscle onset automatic postural responses people multiple sclerosis healthy controls abstractbackgroundplantar sensation critical balance control people multiple sclerosis pwms previous research described impact standing balance influence plantar sensation automatic postural responses aprs well understood pwms purpose study characterize relationship plantar sensation aprs pwms controls secondary aim determine whether relationship plantar sensation aprs different across pwms control groupsmethods121 pwms 51 agematched controls underwent forward backward supportsurface perturbations stance onset tibialis anterior ta medial gastrocnemius mg primary reactive balance outcome measures backward forward losses balance respectively plantar sensation measured vibration sensation threshold vt resultsas expected pwms significantly higher ie worse vt p0001 increased mg ta onset latency ta p0001 mg p001 compared control group higher vt related increased mg p0001 ta latency p0001 across participants however moderating effect group control pwms observed relationship vt muscle onset mg p014 ta p034 conclusionpwms poorer plantar sensation delayed muscle onset aprs compared controls plantar sensation related muscle onset perturbations participants although relationship moderated group may related lack dynamic range vt scores controls results indicate plantar sensation likely related reactive balance provides insight potential contributing factor delayed automatic postural reactions people ms,0.0
novel fatty acidbinding protein 5 7 inhibitor ameliorates oligodendrocyte injury multiple sclerosis mouse models abstractbackgroundmultiple sclerosis ms autoimmune disease characterised demyelination mature oligodendrocytes central nervous system recently several studies indicated vital roles fatty acidbinding proteins fabps 5 7 regulating immune responsemethodswe assessed novel fabp5 fabp7 inhibitor fabp ligand 6 mf 6 potential therapeutic ms therapy vivo established mog3555administered experimental autoimmune encephalomyelitis eae mice ms mouse model followed prophylactic symptomatic treatment mf 6 therapeutic effect mf 6 determined using behavioural biochemical analyses vitro mf 6 effects astrocytes oligodendrocytes examined using astrocyte primary culture kg1c cell linesfindingsprophylactic symptomatic mf 6 therapy reduced myelin loss clinical eae symptoms furthermore oxidative stress levels gfappositive ionised calciumbinding adaptor protein1positive cells reduced spinal cord mf 6treated mice addition mf 6 attenuated lipopolysaccharidestimulated interleukin1 tumour necrosis factor accumulation primary astrocyte culture moreover mf 6 indicated powerful protective function mitochondria oligodendrocytes eae mice via fabp5 inhibitioninterpretationsmf 6 potent inhibitor fabp5 fabp7 targeted inhibition two proteins may confer potential therapeutic effects ms via immune inhibition oligodendrocyte protectionfundingthis work supported strategic research program brain sciences japan agency medical research development jp17dm0107071 jp18dm0107071 jp19dm0107071 jp20dm0107071,1.0
intrapopulation differences apolipoproteins aqueous humor background evidence suggests proteins related lipid metabolism apolipoproteins play important role maintenance normal vision several members apolipoprotein family abundant human aqueous humor ah study remains difficult due ahs small volume low protein concentration invasive nature sample collection study report use liquid chromatography tandem mass spectrometry lcms ms discover associations ah apolipoproteins race gender ocular structure patients without primary open angle glaucoma poag methodsah samples collected 231 patients undergoing phacoemulsification glaucoma incisional surgery medical college georgia augusta university subsequently analyzed via lcms ms number peptide spectrum matches psms protein used semiquantitative measure relative protein levels parameters related ocular structure determined using optical coherence tomography oct heidelberg retinal tomography hrt data sets probed relationships apolipoprotein levels poag demographics gender race ocular structureresultsa total ten apolipoproteins detected 231 collected ah samples six detected 100 samples one detected almost 57 samples three detected less 10 samples levels apoa1 apoc3 apod higher among poag subjects stratification gender race revealed demographicspecific variations levels five apolipoproteins apoa1 apoa2 apoa4 apoc3 apod higher female poag patients whereas apolipoprotein levels altered male poag patients levels apoa1 apoa2 apoa4 apod increased glaucomatous african american patients whereas apoe apoh levels decreased glaucomatous caucasian patients also found distinct associations apolipoprotein levels oct hrt parameters patients without poagconclusionsthe intrapopulation variation apolipoprotein levels highlights heterogeneity glaucoma disease suggesting importance personalized treatments gender racespecific alterations may associated higher risks poag females members african american population,0.0
differential chemokine alteration variants primary progressive aphasiaa role neuroinflammation background primary progressive aphasias ppa represent group usually sporadic neurodegenerative disorders three main variants nonfluent agrammatic variant nfvppa semantic variant svppa logopenic variant lvppa usually associated specific underlying pathology nfvppa primary tauopathy svppa tdp43 proteinopathy lvppa underlying alzheimers disease ad little known cause pathophysiology prior studies ad svppa suggested role neuroinflammation study set investigate role chemokines across ppa spectrum primary focus central changes cerebrospinal fluid csf methodsthirtysix participants sporadic ppa 11 svppa 13 nfvppa 12 lvppa well 19 healthy controls recruited study donated csf plasma samples patients lvppa tau a42 biomarker profile consistent ad whilst normal ppa groups controls assessed twenty chemokines csf plasma using proximity extension assay technology ccl2 mcp1 ccl3 mip1a ccl4 mip1 ccl7 mcp3 ccl8 mcp2 ccl11 eotaxin ccl13 mcp4 ccl19 ccl20 ccl23 ccl25 ccl28 cx3cl1 fractalkine cxcl1 cxcl5 cxcl6 cxcl8 il8 cxcl9 cxcl10 cxcl11resultsin csf ccl19 cxcl6 decreased svppa nfvppa compared controls whilst cxcl5 decreased nfvppa group borderline significant decrease svppa group contrast ccl2 ccl3 cx3cl1 increased lvppa compared controls nfvppa greater svppa cx3cl1 cxcl1 also increased lvppa compared nfvppa groups cx3cl1 significantly correlated csf total tau concentrations controls ppa groups fewer significant differences seen groups plasma although general results opposite direction csf ie decreased lvppa compared controls ccl3 ccl19 increased svppa ccl8 nfvppa ccl13 conclusiondifferential alteration chemokines across ppa variants seen csf plasma importantly results suggest role neuroinflammation poorly understood sporadic disorders therefore also potential future therapeutic target,0.0
sociodemographic clinical characteristics diet adherence relationship diet quality international cohort people multiple sclerosis abstractbackground diet associated onset progression multiple sclerosis ms multiple diets varying recommendations proposed beneficial people ms characteristics follow specific dietprograms relationships dietprograms diet quality underexploredmethods data holism study analysed adherence selected msspecific diets ashton embry best bet mcdougall overcoming ms oms palaeolithic swank wahls elimination queried 5point likert scales moderate 3 5 rigorous 4 5 adherence defined sociodemographic clinical characteristics adherence evaluated logbinomial regression relationships dietprogram adherence diet quality assessed linear logbinomial regression appropriate characteristics diet quality measured diet habits questionnaire assessed linear regression multivariable models adjusted age sex socioeconomic status ses education clinically significant fatigueresults fortynine percent participants reported least 12month adherence dietprogram ms 313 rigorously adhered oms 49 swank 17 wahls 15 dietprograms adherence dietprogram oms wahls swank quantitatively assessed females participants lowerthanaverage ses longer disease duration less adherent dietprogram ms well higher disability clinically significant fatigue greater depression risk comorbidities higherthanaverage ses adherent higher physical mental quality life similar relationships seen oms dietprogram adherence adherence wahls dietprogram higher among progressive ms types longer disease duration associations found adherence swank dietprogram overall diet quality higher among participants following dietprogram particularly oms swank wahlsconclusion greater adherence ms specific diets associated higher ses higher quality life following diet program associated higher overall diet quality adhering oms diet highest diet quality results may inform health professionals providing guidance patients regarding diet ms,0.0
acute relapse poor immunization following covid19 vaccination rituximabtreated multiple sclerosis patient hum vaccin immunother 2021 may 2013 doi 101080 2164551520211928463 online ahead printabstractwith progress covid19 vaccination programs worldwide new adverse events associated available vaccines may unfold especially subpopulations representatives included phase ii iii clinical trials vaccines patients autoimmune diseases including multiple sclerosis ms 34yearold woman presented severe right hemiplegia ataxia diagnosed relapsingremitting ms rrms 13 years ago treated rituximab anticd20 monoclonal antibody last 15 months received first dose adenovirusvectored covid19 vaccine gamcovidvac sputnik v three months last infusion rituximab three days experiencing latest ms relapse episode preceded mild symptoms fatigue myalgia generalized weakness etc magnetic resonance imaging revealed several new periventricular juxtacortical brainstem cerebellar peduncle lesions received corticosteroid therapy five consecutive days neurological deficits slightly improved twentyone days receiving first dose vaccine antisarscov2 antibodies lower detection limit however decision made adhere vaccination schedule risk patients safety unfortunate covid19 contraction thus advised receive second gamcovidvac dose discontinuation oral steroid taper safety adenovirusbased vaccines patients autoimmune diseases requires investigation meanwhile clinicians raise awareness among patients regarding potentially limited efficacy covid19 vaccination treated anticd20 treatments careful individualized riskbenefit assessments planning delay pause treatments create time window patients receive vaccine develop antisarscov2 immunity may recommendedpmid34015240 doi101080 2164551520211928463,0.0
distinct b cell subsets peyers patches convey probiotic effects limosilactobacillus reuteri background intestinal peyers patches pps form unique niches bacteriaimmune cell interactions direct host immunity shape microbiome investigate peroral administration probiotic bacterium limosilactobacillus reuteri r2lc affects b lymphocytes iga induction pps well downstream consequences intestinal microbiota susceptibility inflammationresultsthe b cells pps separated size circumvent activationdependent cell identification biases due dynamic expression markers resulted two phenotypically transcriptionally spatially distinct subsets small igd+ gl7 s1pr1+ bcl6 ccr6expressing pregerminal center gc like b cells innatelike functions located subepithelially large gl7+ s1pr1 ki67+ bcl6 cd69expressing b cells strong metabolic activity found gc peroral l reuteri administration expanded b cell subsets enhanced innatelike properties pregclike b cells retaining subepithelial compartment increased sphingosine1phosphate s1pr1 signaling furthermore l reuteri promoted gclike b cell differentiation involved expansion gc area autocrine tgf1 activation consequently pd1t follicular helper celldependent iga induction production increased l reuteri shifted intestinal microbiome protected dextransulfatesodium induced colitis dysbiosisconclusionsthe peyers patches sense enhance transmit probiotic signals increasing numbers effector functions distinct b cell subsets resulting increased iga production altered intestinal microbiota protection inflammation video abstract,0.0
epilepsy predictor disease progression multiple sclerosis abstractbackgroundepilepsy development course multiple sclerosis ms considered result cortical pathology however longterm data exist whether epilepsy ms also leads increasing disability timeobjectiveto examine epilepsy leads rapid disease progressionmethodswe analyzed data 31 052 patients german multiple sclerosis register casecontrol studyresultssecondary progressive disease course odds ratio 223 age 112 per 10years disability 129 per expanded disability status scale edss point associated 5year prevalence epilepsy patients developed epilepsy course disease higher edss score disease onset compared matched control patients edss 20 vs 15 progressed faster dimension consequently showed higher disability edss 44 vs 34 lower employment status 40 vs 65 final followup 15years ms 64 patients without compared 54 patients epilepsy severely limited walking distanceconclusionthis work highlights association epilepsy disability progression ms need additional data clarify underlying mechanisms,0.0
analysis application glucocorticoids eight pediatric neurological disorders china zhonghua er ke za zhi 2021 oct 2 59 10 847852 doi 103760 cmajcn1121402021032300246abstractobjective investigate application glucocorticoids children neurological diseases pediatricians provide baseline data standardization glucocorticoids application methods crosssectional survey electronic questionnaire survey conducted online july 8 2019 july 28 2019 subspecialty group clinical pharmacology subspecialty group neurology expert committee rational use medicines children society pediatrics chinese medical association survey conducted application glucocorticoids 8 neurological diseases children compared current guidelines consensus judge whether application standard total 1 850 pediatricians 1 073 hospitals surveyed surveyed diseases included bacterial meningitis antinmethyldaspartate receptor encephalitis neuromyelitis optica spectrum disease nmosd multiple sclerosis guillainbarre syndrome myasthenia gravis juvenile dermatomyositis duchenne muscular dystrophy order explore associated factors standardized glucocorticoid application level hospital whether independent department pediatric neurology working experience doctor used independent variables 2 test multivariate logistic analysis used statistical analysis results total 1 834 991 valid questionnaires collected 1 073 hospitals 31 provinces autonomous regions municipalities coincidence rate recommendation current guideline consensus glucocorticoids 58 51 879 juvenile dermatomyositis 137 153 1 115 myasthenia gravis 182 142 781 bacterial meningitis 185 310 1 680 antinmethyldaspartate receptor encephalitis 230 248 1 079 duchenne muscular dystrophy 334 322 964 nmosd multiple sclerosis 435 477 1 096 guillainbarre syndrome common one irregular course treatment coincidence rate 368 125622 multivariate logistic regression analysis indicated use glucocorticoids standardized bacterial meningitis or183 95ci 139243 p001 guillainbarre syndrome or197 95ci 150259 p001 duchenne muscular dystrophy or185 95ci 138248 p001 juvenile dermatomyositis or208 95ci 103419 p0040 nmethyldaspartate receptor encephalitis or0302 95ci 020046 p001 pediatricians pediatric neurology specialty hospital conclusions coincidence rate recommendation current guideline consensus glucocorticoids less half children neurological diseases use glucocorticoids standardized variety diseases pediatricians pediatric neurology specialty hospital indicates study guidelines consensus special training pediatric neurologists strengthenedpmid34587681 doi103760 cmajcn1121402021032300246,0.0
restless legs syndrome pediatric onset multiple sclerosis abstractbackgroundrestless legs syndrome willisekbom disease rls wed shown high prevalence among adults multiple sclerosis ms objectivewe aimed investigate prevalence rls wed define disease characteristics young patients pediatric onset multiple sclerosis poms method50 patients poms questioned presence rls wed demographic clinical laboratory data compared poms patients without rls wed including total number clinical radiological ms attacks interval first two attacks edss number hyperintense contrastenhancing lesions localization demyelinating lesions igg index cerebrospinal fluid oligoclonal band serum ferritin creactive protein ratio neutrophil lymphocyte count 25hydroxy vitamindresultseleven patients 22 rls wed mostly moderate severity 545 mean edss score significantly higher poms patients rls wed without p0003 ig g index almost two times higher poms patients rls wed failed reach statistically significant level p0073 conclusionour study demonstrated high prevalence rls wed young patients poms higher edss scores patients poms rls wed indicates diseaserelated factors emergence rls wed,1.0
analysis 13 cases pediatric rheumatic disease combined endocrine disorder zhonghua er ke za zhi 2021 oct 2 59 10 865870 doi 103760 cmajcn1121402021030300178abstractobjective summarize clinical characteristics children rheumatic disease combined endocrine disorder methods retrospective analysis performed clinical data including sex age clinical presentation laboratory tests treatment outcome 13 patients rheumatic diseases combined endocrine disorder admitted department childrens hospital capital institute pediatrics january 2014 december 2020 results among 13 cases 3 males 10 females without family history age 104 years average course disease 41 months eight diagnosed systemic lupus erythematosus jsle 2 juvenile idiopathic arthritis jia 1 childhood vasculitis 1 juvenileonset systemic sclerosis jssc 1 juvenile dermatomyositis jdm regarding initial presentation 10 cases symptoms rheumatic disease 2 polydipsia polyuria 1 goiter 13 patients multiple system involvement regarding endocrine disorder 10 thyroiditis subclinical thyroiditis 4 diabetes mellitus one thyroid pancreas involvement thyroid stimulating hormone 10 patient thyroid involvment 196 52340 mu l total thyroxine 753 4521054 nmol l besides thyroid peroxidase antibody thyroglobulin antibody positive 7 cases blood glucose 4 children pancreatic injury 250 170330 mmol l cpeptide 04 0305 mg l glutamate dehydrogenase antibody protein tyrosine phosphatase antibody zinc transporter 8 antibody positive two cases treatement immunosuppressant immunoglobulin combined glucocorticoid nonsteroidal antiinflammatory drugs rheumatic symptoms levothyroxine insulin endocrine diseases followed 6 months maintained clinical stability conclusions rheumatic diseases children can complicated endocrine disorders involved organs usually thyroid pancreas children rheumatic disease thyroid injury usually subtle onset whereas pancreas injury develops rapidly even lifethreatening insulin used persistently instruction endocrinologistpmid34587684 doi103760 cmajcn1121402021030300178,0.0
interleukin1 receptor associated kinase 4 deficiency case report literature review zhonghua er ke za zhi 2021 oct 2 59 10 876880 doi 103760 cmajcn1121402021030900191abstractobjective summarize clinical characteristics children interleukin1 receptor associated kinase 4 irak4 deficiency methods clinical data child irak4 deficiency admitted department neurology shenzhen childrens hospital several times june 2019 august 2020 retrospectively analyzed related literature january 2021 key words irak4 gene variation interleukin1 receptorassociated kinase 4 deficiency pubmed cnki wanfang cqvip databases searched clinical characteristics disease summarized analyzed results boy 6 years age recurrent respiratory tract infections improved antibiotic treatment clinical manifestation included streptococcus pneumoniae meningoencephalitis multiple sclerosis invasive discitis inflammatory bone destruction familybased whole exome sequencing showed boy homozygous frameshift variation irak4 gene nm_0161233c540del pphe180leufs26 parents heterozygous total 23 cases reported ten english articles together case 24 cases including 13 males 11 females age onset 8 days 7 years main manifestations recurrent invasive bacterial infection including 11 cases streptococcus pneumoniae meningitis 9 cases streptococcus pneumoniae staphylococcus aureus septicemia 1 case pseudomonas aeruginosa meningitis 1 case salmonella infection 1 case staphylococcus aureus skin abscess 1 case recurrent virus infection 2 patients autoimmune diseases 1 autoimmune encephalitis one juvenile idiopathic arthritis among 24 cases 10 died 9 infancy surviving children diagnosed early received antibiotics preventively intravenous immunoglobulin ivig susceptibility infection decreased year year close normal children age 14 years among 24 cases 21 cases homozygous variation irak4 gene 3 cases complex heterozygous variation 15 kinds variation including 9 kinds frameshift variation 4 kinds nonsense variation 2 kinds missense variation one candidate variation hotspot c877 ct 3 cases conclusions irak4 deficiency mainly manifest recurrent invasive bacterial infection streptococcus pneumoniae meningitis septicemia common patients complicated autoimmune diseases mortality rate high infancy early diagnosis treatment can avoid severe illness deathpmid34587686 doi103760 cmajcn1121402021030900191,0.0
cardiorespiratory fitness freeliving physical activity associated cognition persons progressive multiple sclerosis baseline analyses cogex study abstractbackgroundaerobic exercise training physical activity improving cardiorespiratory fitness represents promising approach managing cognitive impairment multiple sclerosis ms however limited evidence levels physical activity fitness associated cognition progressive msobjectivewe examined associations among cardiorespiratory fitness moderatetovigorous physical activity mvpa cognitive performance large international progressive ms samplemethodstwo hundred forty european north american persons progressive ms underwent cardiorespiratory fitness measurement recumbent stepper wore actigraph gt3x+accelerometer 7days measuring mvpa underwent brief international cognitive assessment msresultscardiorespiratory fitness significantly correlated symbol digit modalities test sdmt r001 r004 california verbal learning testii cvltii r005 r005 brief visuospatial memory testrevised bvmtr r014 r014 zscores controlling age sex education mvpa sdmt r005 cvltii r007 bvmtr r001 zscores significantly correlatedconclusioncardiorespiratory fitness mvpa associated cognition large progressive ms sample yet outcomes represent critical manipulation checks documenting success cogex trial highlights importance examining exerciserelated mechanismsofaction improving cognition progressive ms,0.0
humoral immune response covid19 multiple sclerosis nationwide austrian study abstractbackgroundknowledge immunity sarscov2 infection patients multiple sclerosis pwms impact diseasemodifying treatment dmt limitedobjectiveto evaluate degree duration potential predictors specific humoral immune response pwms prior covid19methodsantisarscov2 antibody testing performed pwms pcrconfirmed diagnosis symptomatic covid19 nationwide registry predictors seropositivity identified multivariate regression modelsresultsin 125 pwms mean age 424years sd 123 years 70 female antisarscov2 antibodies detected 760 median 52months positive pcr seropositivity rate significantly lower patients isdmt 614 p0001 without dmt immunomodulatory dmt 806 860 respectively multivariate analysis isdmt associated reduced probability seropositivity odds ratio 051 95 confidence interval 95 ci 017082 p0001 predefined subgroup analyses showed marked reduction seropositivity pwms rituximab ocrelizumab 015 95 ci 005056 p0001 rate seropositivity change significantly 6monthsconclusionshumoral immunity stable sarscov2 infection ms reduced immunosuppressive dmt particularly anticd20 monoclonal antibodies provides important evidence advising pwms well planning prioritizing vaccination,0.0
longterm efficacy safety inebilizumab neuromyelitis optica spectrum disorder analysis aquaporin4immunoglobulin gseropositive participants taking inebilizumab 4years nmomentum trial backgroundefficacy safety inebilizumab treatment neuromyelitis optica spectrum disorder adults seropositive aquaporin4 aqp4 immunoglobulin ig g demonstrated 28week randomized controlled period nmomentum studyobjectiveto assess efficacy safety longterm inebilizumab treatmentmethodspost hoc analysis performed 75 aqp4iggseropositive participants receiving inebilizumab 4years randomized controlled period openlabel extension nmomentum studyresultseighteen attacks occurred 13 participants inebilizumab treatment annualized attack rate 0052 attacks personyear twelve attacks occurred first year treatment two occurred years 24 disability scores remained stable throughout 4years treatment inebilizumab well tolerated two 27 serious treatmentemergent adverse events related inebilizumab deaths immunoglobulin g levels decreased time however correlation severe infections low igg levels determined small numbersconclusionthese results nmomentum study continue support use inebilizumab treatment neuromyelitis optica spectrum disorder furthermore findings suggest efficacy inebilizumab may enhanced first year treatment warranting additional longterm investigation,1.0
free falls education exercise program reducing falls people multiple sclerosis randomized controlled trial abstractbackgroundpeople multiple sclerosis pwms fall frequently communitydelivered exercise education reduce falls older adults efficacy multiple sclerosis ms unknownobjectivesto evaluate impact free falls fff group education exercise program falls pwmsmethodsthis prospective assessorblinded twoarm parallel randomized controlled trial ninetysix participants randomized fff eight weekly 2hour sessions control condition fall prevention brochure informing neurologist fall history participants counted falls prospectively enrollment 6months following intervention effects fall frequency evaluated bayesian analysisresultsthe modeled mean fall frequency preintervention 12 falls month fff group 95 credible intervals cis 0820 14 falls month control group 95 ci 0921 fall frequency decreased 06 falls month groups time nadir 46months postintervention fff 06 falls month 95 ci 0409 control 08 falls month 95 ci 0511 conclusioninperson group exercise education superior written education neurologistinitiated interventions preventing falls pwms,0.0
diminished seroconversion following single sarscov2 vaccine ocrelizumabtreated relapsingremitting multiple sclerosis patients abstractbackgrounddespite impressive efficacy immunocompetent individuals immunogenicity single dose covid19 vaccine bcelldeplete patients remains unknownobjectiveswe aimed quantify realworld vaccine immunogenicity ocrelizumab recipientsmethodswe measured postvaccination sarscov2 immunoglobulin g igg ocrelizumab recipients using highly sensitive luminex assayresults441 patients detectable sarscov2igg 21+ days one vaccine dose regardless vaccine type azd1222 vs bnt162b2 odds ratio 062 95 confidence interval ci 0157232 p 072 bcell count strongly predicted seroconversion 1 1238 95 ci 4592016 p 00029 undetectable bcells preclude second vaccine seroconverted 53 patients already responded dose 1conclusionhumoral response one covid19 vaccine dose lower expected cd20deplete patients,0.0
clinical features combined central peripheral demyelination antibodies node ranvier abstractbackgroundcombined central peripheral demyelination ccpd disease inflammatory demyelination affects central peripheral nerves simultaneously temporally separatedobjectivesthis study evaluated clinical characteristics existence antinodal paranodal antibodies patients ccpdmethodswe reviewed clinical manifestations laboratory tests electrophysiological examinations neuroimaging findings treatment prognosis 31 patients ccpd using live cellbased assay tested antinodal paranodal antibodiesresultsthe common symptoms motor weakness 833 hyporeflexia 633 sphincter disturbance 581 total 166 patients impaired vision symptoms whereas 333 patients abnormal visualevoked potentials veps total 211 4 19 patients positive antiaqp4 aquaporin 4 antibodies 200 2 10 patients positive antinf155 neurofascin155 antibodies 100 1 10 patients positive antimag myelinassociated glycoprotein antibodies effective rates intravenous corticosteroids intravenous immunoglobulins rituximab 722 375 100 respectively illness peak 75 patients ccpd mrs modified rankin scale score 4 greater remission 375 mrs score 4 greaterconclusionthe clinical manifestations patients ccpd highly heterogeneous recommend testing antinodal paranodal antibodies patients ccpd,1.0
biosimilars treatment multiple sclerosis iran arch iran med 2021 oct 1 24 10 779782 doi 1034172 aim2021115abstractbiological drugs manufactured via changes made living organisms genetic engineering notably biological drugs expensive importation can impose economic pressure especially poorer countries thereafter manufacturing drugs considered policymakers many countries resulting production biosimilars iran requires wide range biological drugs due growing number patients multiple sclerosis hand poor economic situation iran due repeated sanctions great impact health care system prevented allocation sufficient financial resources regard therefore manufacturing biosimilar drugs due lower cost received much attention various fields treatmentpmid34816701 doi1034172 aim2021115,0.0
gray matter atrophy relapsingremitting multiple sclerosis associated white matter lesions connecting fibers abstractbackgroundlesions brain white matter wm atrophy brain gray matter gm wellestablished surrogate parameters multiple sclerosis ms unclear closely parameters relate otherobjectiveto assess across whole cerebrum whether gm atrophy can explained lesions connecting wm tractsmethodsgm images 600 patients relapsingremitting ms women 68 median age 330years median expanded disability status scale score 15 converted atrophy maps data healthy control cohort atlas wm tracts human connectome project individual lesion maps merged identify potentially disconnected gm regions leading individual disconnectome maps across whole cerebrum gm atrophy potentially disconnected gm tested association crosssectionally longitudinallyresultswe found highly significant correlations disconnection atrophy across cerebrum longitudinal analysis demonstrated close temporal relation wm lesion formation gm atrophy connecting fibersconclusiongm atrophy associated wm lesions connecting fibers caution warranted interpreting group differences gm atrophy exclusively differences early neurodegeneration independent wm lesion formation,0.0
chewing fat emerging target multiple sclerosis article ebiomedicine cheng colleagues show blocking function fatty acidbinding proteins fabps pharmacologically alleviates severity inflammatory demyelinating neurological condition experimental autoimmune encephalomyelitis eae mouse model 1 suggesting targeting lipid metabolism may viable therapeutic strategy several pathological hallmarks multiple sclerosis ms appreciate finding need examine role fabp relationship msn ms multifactorial autoimmune neurodegenerative condition presence proinflammation brought reactive t cells microglia astrocytes oxidative stress mitochondrial dysfunction perpetuate degeneration neurons glial cells including oligodendrocytes common hallmarks early ms hence therapeutic targets suppress proinflammatory activities immune cells astrocytes promote remyelination capability oligodendrocytes priorities ms researchn fatty acids known involved inflammatory response oxidative stress mitochondrial dysfunction processes relevant ms moreover myelin lipidrich membrane structure production dependent fatty acid synthesis made oligodendrocytes 2 makes lipid metabolism modulation key therapeutic target considering increased adiposity risk factor linked increased disability ms postulated inflammation ms secondary consequence dysregulated lipid metabolismn fabps lipid chaperones regulate fatty acid metabolism differential subtype expressions confer tissue cell specificity example brain fabp fabp7 expressed astrocytic cells epidermal fabp fabp5 expressed immune cells microglia early limited clinical evidence showing fabp involved ms recent paper showed increased fabp4 associated higher disability ms patients 3 suggesting fabp modulation attractive therapeutic approach potential cell specific interventions ms development fabp inhibitors currently underwayn several studies targeting fabp limit proinflammation injuries central nervous system demonstrated overlapping pathological hallmarks across neurodegenerative diseases including ms example mice lacking fabp4 5 reduced eae severity associated impaired proinflammatory activities 4 similar outcome can achieved pharmacologically selective inhibitor fabp5 known ei03 5 results still infancy involve animal models primary focus immune modulationn cheng colleagues show mf6 novel ligand binds fab5 7 reduces eae severity attenuates proinflammatory activities limiting reactive astrocytes consistent previous findings 6 authors go provide direct evidence fabp5 7 inhibition limit oxidative stressinduced damage eae targeting reactive microglia protecting oligodendrocytes considered key strategies limiting ms progression mf6 ideal drug candidate specifically target immune cells astrocytes relevant ms pathologyn several questions remain tempting first think inhibiting lipid metabolism may key limiting ms progression least eae model however fatty acids increased ms summarized recent systematic review 7 decreased beneficial ms oleic acid 8 poses contradictory predicament underlying therapeutic mechanism lipid metabolism inhibition basic research perspective using allornothing approach creates epitome doubleedged sword inhibiting fabps also inhibit beneficial fatty acids ms potential sideeffects longterm use need multimodal treatmentn although mf6 shown welltolerated animal study factors need considered recent epigenomewide study showed narcolepsy sleep disorder ms overlapping dna methylation fabp7 suggesting downregulation inhibition may impact sleep physiology 9 prominent problem ms community potential issues need addressed also presents opportunities noteworthy mention inhibition fabps can increase cellular endocannabinoid anandamide levels 10 can protective effects ms hence inhibition fabps may promising target limited fatty acid metabolismn feasibility modulating complex fatty acid metabolic processes multitarget treatment neuroinflammatory degenerative conditions ms requires precise mechanistic control including disease timing cell specificity host fatty acid metabolome profiles achieve holistic precision medicine approach findings presented study make even case targeting multiple cell types responsible proinflammation oxidative stress mitochondrial dysfunction myelination signals exciting time next generation treatments targeting fabp ms possibly neurodegenerative diseases share overlapping pathologiesn,1.0
neuromyelitis optica brain stem involvement middleaged ethiopian woman case report review literature abstractintroductionneuromyelitis optica demyelinating disease central nervous system predominantly affects optic nerves spinal cord neuromyelitis optica white blood cells antibodies primarily attack optic nerves spinal cord may also attack brain brainstem manifestation described recently far neuromyelitis optica rare ethiopia two case reports first case report neuromyelitis optica brainstem involvementcase presentationa 47yearold addis ababa woman presented saint pauls hospital millennium medical college history visual loss 7 years bilateral lower limb weakness 4 days duration bilateral oculomotor nerve palsy past medical history showed systemic hypertension 18 years dyslipidemia 1 year objective evaluation patient revealed right optic nerve atrophy suggesting optic neuritis flaccid paraplegia sensory level fourth thoracic vertebra diagnostic workup using electromyography spinal magnetic resonance imaging revealed demyelinating anterior visual pathway dysfunction signs extensive cervicothoracic transverse myelitis third cervical lower thoracic vertebrae respectively diagnosis neuromyelitis optica established treatment highdose systemic steroid followed azathioprine patient stable several months significant improvement vision lowerextremity weakness relapse symptomsconclusionthe case described rare inflammatory demyelinating disorder central nervous system occurring east africa reminds clinicians suspect neuromyelitis optica patient presented unexplained recurrent optic neuritis make timely diagnosis prevention permanent neuronal damage neuromyelitis optica can also associated oculomotor nerve involvement,1.0
comparison spinal cord magnetic resonance imaging features among children acquired demyelinating syndromes jama netw open 2021 oct 1 4 10 e2128871 doi 101001 jamanetworkopen202128871abstractimportance recognition magnetic resonance imaging mri features associated distinct causes myelitis children essential guide investigations support diagnostic categorizationobjective determine clinical mri features outcomes associated spinal cord involvement pediatric myelin oligodendrocyte glycoprotein antibodyassociated disease mogad multiple sclerosis ms seronegative monophasic myelitisdesign setting participants cohort study participants recruited 2004 2017 multicenter canadian pediatric demyelinating disease study enrolled youth younger 18 years presenting within 90 days acquired demyelinating syndrome 430 participants recruited lesions available spine mri antimog testing performed archived samples obtained close clinical presentation selected participants poorquality images final diagnoses nondemyelinating disease antiaquaporin 4 antibody positivity relapsing seronegative myelitis excluded data analysis performed december 2019 november 2020main outcomes measures spinal cord involvement evaluated 324 mri sequences reviewers blinded clinical serological brain mri findings associated clinical features disability scores 5 years followup retrieved results compared groupsresults total 107 participants median iqr age onset 1114 5591339 years 55 girls 51 included analyses 40 children mogad 21 ms 46 seronegative myelitis longitudinally extensive lesions common among children mogad 30 40 children 75 less common among seronegative myelitis 20 46 children 43 rare children ms 1 21 children 5 axial gray matter t2hyperintensity ie hsign observed 22 35 children 63 mogad 14 42 children 33 seronegative myelitis none ms presence leptomeningeal enhancement highly suggestive mogad 22 32 children 69 mogad vs 10 38 children 26 seronegative myelitis 1 15 children 7 ms children mogad likely complete lesion resolution serial images 14 21 children 67 compared ms 0 13 children conclusions relevance findings suggest several features may help identify children presentation likely myelitis associated mogad prominent involvement gray matter leptomeningeal enhancement common pediatric mogad although pathological underpinning observations requires studypmid34643718 doi101001 jamanetworkopen202128871,1.0
role chaperonemediated autophagy pathophysiology including pulmonary disorders abstractautophagy highly conserved mechanism delivering cytoplasmic components lysosomal degradation among three major autophagic pathways chaperonemediated autophagy cma primarily characterized selective nature protein degradation mediated heat shock cognate 71 kda protein hsc70 also known hspa8 recognition kferq peptide motif target proteins lysosomeassociated membrane protein type 2a lamp2a responsible substrate binding internalization lysosomes thus lysosomal expression level lamp2a ratelimiting factor cma recent advances uncovered physiological also pathological role cma multiple organs including neurodegenerative disorders kidney diseases liver diseases heart diseases cancers accumulation unwanted proteins increased degradation target proteins concomitant metabolic alterations resulting cma malfunction respect pulmonary disorders involvement cma demonstrated lung cancer chronic obstructive pulmonary disease copd pathogenesis regulating apoptosis understanding cma machinery may shed light molecular mechanisms refractory disorders lead novel treatment modalities cma modulation,0.0
amyotrophic lateral sclerosis systemic disease peripheral contributions inflammationmediated neurodegeneration curr opin neurol 2021 aug 16 doi 101097 wco0000000000000983 online ahead printabstractpurpose review neuroinflammation important mediator pathogenesis disease amyotrophic lateral sclerosis als genetic mutations c9orf72 begun define numerous cell autonomous pathways initiate motor neuron injury yet signalling surrounding glia peripherally derived immune cells initiates noncell autonomous inflammatory process promotes selfpropagating motor neuron cell death purpose review explore systemic immune inflammatory contributions pathogenesis als peripheral proinflammatory signatures initiates presence represent potential therapeutic targetsrecent findings als motor neuron cell death initiated multiple cell autonomous pathways leading misfolded proteins oxidative stress altered mitochondria impaired autophagy altered rna metabolism collectively promote noncell autonomous inflammatory reactivity resulting disease characterized activated microglia astrocytes well peripherally derived proinflammatory innate adaptive immune cells unrelenting disorder circulating blood monocytes natural killer cells proinflammatory furthermore regulatory t lymphocytes dysfunctional proinflammatory cytokines acute phase proteins elevatedsummary collective dysregulation cells cytokines patients als accurately reflect increased disease burdens rapid progression rates reduced survival times reinforcing concept als disorder extensive systemic proinflammatory responses increased systemic proinflammatory immune constituents provide potentially meaningful therapeutic targetspmid34402459 doi101097 wco0000000000000983,0.0
pregnancy multiple sclerosis update curr opin obstet gynecol 2021 jul 22 doi 101097 gco0000000000000731 online ahead printabstractpurpose review provide latest evidence treatment advances multiple sclerosis women childbearing age prior conception pregnancy postpartumrecent findings recent changes permitting interferon beta ifn use pregnancy breastfeeding broadened choices disease modifying treatments dmts patients high relapse rates natalizumab may also continued 34 weeks pregnancy patients requiring persisting treatment drugs known potential teratogenicity fingolimod teriflunomide avoided recommended washout times medications cladribine alemtuzumab ocrelizumab considered teriflunomide fingolimod recommended breastfeeding however glatiramer acetate ifn considered safesummary evidence potential fetotoxicities adverse pregnancy outcomes associated dmts increasing although research needed evaluate safety drugs track longterm health outcomes mother childpmid34310364 doi101097 gco0000000000000731,0.0
evaluation edaravone effects differentiation human adipose derived stem cells oligodendrocyte cells multiple sclerosis disease rats life sci 2021 jul 12119812 doi 101016 jlfs2021119812 online ahead printabstractaims among treatments multiple sclerosis stem cell transplantation adscs attracted great deal scientific attention hand edaravone antioxidant component combination stem cells increase survival differentiation potential stem cellsmain methods 42 rats divided control cuprizone cpz sham edaravone ed hadscs ed hadscs groups following induction cuprizone induced ms model behavioral tests designed evaluate motor function luxal fast blue staining done measure level demyelination remyelination immunofluorescent staining used evaluate amount mbp olig2 mog proteins mrna levels human mbp mog olig2 rat mbp mog olig2 determined via rtpcrkey findings flow cytometry analysis exhibited extracted cells positive cd73 938 3 cd105 916 3 yet negative cd45 206 05 behavioral tests unveiled significant improvement ed p 0001 hadscs p 0001 ed hadscs p 0001 groups compared others ed hadscs group myelin density significantly higher ed treated hadscs treated groups p 001 edaravone hadscs increased expression mbp mog olig2 genes cuprizone rat models moreover significant differences seen ed treated hadscs treated groups ed hadscs group p 005 mbp olig2 p 001 mog significance edaravone combination hadscs reduced demyelination increased oligodendrogenesis cuprizone rat modelspmid34265362 doi101016 jlfs2021119812,1.0
evaluation impact lockdown health lifestyle users fundacio esclerosi multiple#39 s neurorehabilitation centres lleida reus rev neurol 2021 oct 1 73 7 249257 doi 1033588 rn73072020640abstractintroduction 13 march 2020 state alarm declared due covid19 pandemic resulting total lockdown spain neurorehabilitation centres fundacio esclerosi multiple fem provide care people diagnosed neuroprogressive diseases significant health deficits look lockdown can affect way lifeaims assess manage impact lockdown persons multiple sclerosis ms neurodegenerative diseasespatients methods analytical observational study anonymous questionnaire administered patients undergoing comprehensive rehabilitation treatment two fem centres survey included questions demographic clinical characteristics subjects assessment impact pandemic physical social psychological spheresresults total 202 surveys analysed average age participants 4909 years 778 ms 222 conditions frequently reported physical symptoms muscle weakness loss balance fatigue study population remained active lockdown half report increase cognitive symptoms mention increased sense worry emotional levelconclusions can state actions deployed fem reduce consequences lockdown effective minimised occurrence maladaptive behaviours study also opened door us add new lines interventionpmid34569035 doi1033588 rn73072020640,0.0
factors associated use complementary therapies taiwanese patients systemic lupus erythematosus crosssectional study background study aimed investigate prevalence factors associated regular use complementary therapies taiwanese patients systemic lupus erythematosus sle methodsin crosssectional study 351 patients sle consecutively recruited regional hospital southern taiwan april august 2019 demographic clinical information including use different types complementary therapies ascertained using selfconstructed questionnaire diseasespecific quality life measured using lupus quality life lupusqol questionnaire sle disease activity assessed using rheumatologistscored systemic lupus erythematosus disease activity index 2000 sledai2 k factors associated regular use complementary therapies evaluated using multiple logistic regression analysesresultsof 351 patients sle 903 female 601 40 years age prevalence regular use type complementary therapy 855 five popular types complementary therapy used 1 fitness walking strolling 2 buddhist prayer attending temple 3 vitamin consumption 4 calcium supplementation 5 fish oil supplementation multiple logistic regression analyses revealed significant independent factors associated regular use complementary therapies patients sle age 40 years adjusted odds ratio aor 276 p 0013 nonoverweight nonobesity aor 029 p 0004 engagement vigorous exercise past year aor 462 p 0002 lower sledai2 k score aor 090 p 0029 lower score physical health domain lupusqol aor 057 p 0001 conclusionsa high prevalence complementary therapy use taiwanese patients sle observed rheumatologists routinely ask patients use supplements minimize risk interaction medical therapy,0.0
risk factors time clinical symptoms multiple sclerosis among patients radiologically isolated syndrome jama netw open 2021 oct 1 4 10 e2128271 doi 101001 jamanetworkopen202128271abstractimportance younger age oligoclonal bands infratentorial spinal cord lesions factors associated increased 10year risk clinical conversion radiologically isolated syndrome ris multiple sclerosis ms whether diseasemodifying therapy beneficial individuals ris currently unknownobjectives evaluate 2year risk clinical event onset clinical symptoms ms prospectively identify factors associated developing early clinical event simulate sample size needed phase iii clinical trial individuals ris meeting 2009 ris criteriadesign setting participants cohort study used data prospectively followedup individuals ris identified 1 26 tertiary centers ms care france collect data observatoire franais de la sclrose en plaques database participants aged 10 80 years 2 magnetic resonance imaging mri scans study entry index scan 2000 diagnoses validated expert group whose review included double centralized mri reading data analyzed july 2020 january 2021exposure diagnosis rismain outcomes measures risk clinical event associated covariates index scan analyzed among individuals ris time first clinical event compared covariates sample size estimates modeled based identified risk factorsresults among 372 individuals ris mean sd age index mri scan 386 121 years 354 individuals included analysis 264 746 women clinical event identified among 49 patients 138 within 2 years associated estimated risk conversion 192 95 ci 141240 multivariate analysis age younger 37 years hazard ratio hr 404 95 ci 200815 p 001 spinal cord lesions hr 511 95 ci 1991313 p 001 gadoliniumenhancing lesions index scan hr 209 95 ci 113387 p 02 independently associated increased risk conversion ms 2 factors time index mri scan associated risk 279 95 ci 135399 seminal event within 2 years increasing 909 95 ci 411986 individuals 3 factors 3 risk factors vs none hr 2334 95 ci 9085996 p 001 overall 80 power detect effect size 60 within 24 months total 160 individuals ris needed assuming event rate 20conclusions relevance study found age younger age 37 years spinal cord involvement gadoliniumenhancing lesions index mri scan associated earlier clinical disease relevant number enrolled patients needed detect potential treatment effectpmid34633424 doi101001 jamanetworkopen202128271,0.0
evaluation interactive webbased programme relapse management people multiple sclerosis power ms2 study protocol process evaluation accompanying randomised controlled trial bmj open 2021 oct 1 11 10 e046874 doi 101136 bmjopen2020046874abstractintroduction process evaluations accompanying complex interventions examine implementation process underlying intervention identify mechanisms impact assess contextual factors paper presents protocol process evaluation conducted alongside randomised controlled trial power ms2 trial comprises evaluation webbased complex intervention relapse management 188 people multiple sclerosis conducted 20 centres webbased intervention programme focuses relapse treatment decision making includes decision aid nurseled webinar online chat process evaluation presented aim assess participants responses interactions intervention understand intervention produces changemethods analysis mixed methods design used explore acceptance intervention well use impact participants participants people multiple sclerosis neurologists nurses stakeholders quantitative semistandardised evaluation forms will collected throughout study qualitative semistructured telephone interviews will conducted end study selected participants especially people multiple sclerosis neurologists quantitative data will collected analysed descriptively based results qualitative interviews will conducted analysed thematically results will merged joint display tableethics dissemination process evaluation received ethical approval ethical committee university lbeck reference 19024 findings will disseminated peerreviewed journals conferences meetings relevant patient websitestrial registration number nct04233970pmid34598981 doi101136 bmjopen2020046874,0.0
treatment escalation vs immediate initiation highly effective treatment patients relapsingremitting multiple sclerosis data 2 different national strategies jama neurol 2021 aug 16 doi 101001 jamaneurol20212738 online ahead printabstractimportance treatment strategies relapsingremitting multiple sclerosis rrms vary markedly denmark sweden difference association national strategies clinical outcomes unknownobjective investigate association national differences diseasemodifying treatment dmt strategies rrms disability outcomesdesign setting participants cohort study used data 4861 patients danish swedish national multiple sclerosis ms registries date index dmt initiation january 1 2013 december 31 2016 last recorded visit time data extraction october 2 2019 exposures msspecific dmts initiated observation period included analysismain outcomes measures primary study outcome time 24week confirmed disability worsening secondary outcomes 24week confirmed disability improvement milestone expanded disability status scale scores 3 4 annualized relapse rate time first relapse treatment switching data analyzed using inverse probability treatment weightingbased models using propensity score weight correct comparison imbalance confounders observed baseline 2 countriesresults total 2700 patients swedish ms registry 1867 women 692 mean sd age 361 95 years 2161 patients danish ms registry 1472 women 681 mean sd age 373 94 years started first dmt 2013 2016 included analysis observed mean sd 41 15 years total 1994 danish patients 923 initiated low moderately effective dmt teriflunomide 907 420 165 76 initiated highly effective dmt whereas total 1769 swedish patients 655 initiated low moderately effective dmt teriflunomide 64 24 931 345 initiated highly effective dmt swedish treatment strategy associated 29 reduction rate postbaseline 24week confirmed disability worsening relative danish treatment strategy hazard ratio 071 95 ci 057090 p 004 swedish treatment strategy also associated 24 reduction rate reaching expanded disability status scale score 3 hazard ratio 076 95 ci 060097 p 03 25 reduction rate reaching expanded disability status scale score 4 hazard ratio 075 95 ci 061096 p 01 relative danish patientsconclusions relevance findings study suggest association differences treatment strategies rrms disability outcomes national level escalation treatment efficacy inferior using efficacious dmt initial treatmentpmid34398221 doi101001 jamaneurol20212738,0.0
adem chadox1 ncov19 vaccine case report abstractacute disseminated encephalomyelitis adem inflammatory demyelinating disease central nervous system cns clinically defined acute polyfocal neurological syndrome usually monophasic course adem often occurs infections 510 cases preceded vaccinations several cases adem described severe acute respiratory syndrome coronavirus 2 sarscov2 infection whereas case reported adenovirusvectored mrna covid19 vaccine administration describe case adem presenting 2 weeks receiving first dose chadox1 ncov19 vaccine patient clinical magnetic resonance imaging mri status spontaneously improved rapidly resolved corticosteroids 4month followup showed complete recovery relapses,1.0
neurologist agent exercise rehabilitation multiple sclerosis exerc sport sci rev 2021 may 28 doi 101249 jes0000000000000262 online ahead printabstractthis review hypothesizes neurologist represents linchpin exercise behavior change within comprehensive multiple sclerosis ms care settings based series recent papers developed actionable practice models accomplishing behavior change neurologist primary agent provides tangible next steps exercise promotion mspmid34049322 doi101249 jes0000000000000262,0.0
advances genetic classification amyotrophic lateral sclerosis curr opin neurol 2021 aug 2 doi 101097 wco0000000000000986 online ahead printabstractpurpose review amyotrophic lateral sclerosis als archetypal complex disease wherein disease risk severity majority patients product interaction multiple genetic environmental factors period unprecedented discovery new largescale genomewide association study gwas accelerating discovery risk genes however much observed heritability als undiscovered yet approaching elucidation total genetic architecture will necessary comprehensive disease subclassificationrecent findings summarize recent developments discuss future new machine learning models will help address nonlinear genetic interactions statistical power genetic discovery may boosted reducing searchspace using cellspecific epigenetic profiles expanding scope include genetically correlated phenotypes structural variation somatic heterogeneity consideration environmental modifiers represent significant challenges will require integration multiple technologies multidisciplinary approach including clinicians geneticists pathologistssummary move away fully penetrant mendelian risk genes necessitates new experimental designs new standards validation challenges significant potential reward successful disease subclassification largescale effective personalized medicinepmid34343141 doi101097 wco0000000000000986,0.0
association infectious mononucleosis childhood adolescence risk subsequent multiple sclerosis diagnosis among siblings jama netw open 2021 oct 1 4 10 e2124932 doi 101001 jamanetworkopen202124932abstractimportance epsteinbarr virus acute manifestation infectious mononucleosis im associated increased risk multiple sclerosis ms whether association confounded susceptibility infection still debatedobjective assess whether hospitaldiagnosed im childhood adolescence young adulthood associated subsequent ms diagnosis independent shared familial factorsdesign setting participants populationbased cohort study used swedish total population register identify individuals born sweden january 1 1958 december 31 1994 participants aged 20 years followed january 1 1978 december 31 2018 median followup 1538 iqr 8682355 range 0014096 years data analyzed october 2020 july 2021exposure hospitaldiagnosed im 25 years agemain outcomes measures diagnoses ms 20 years age identified risk ms diagnosis associated im childhood birth 10 years age adolescence 1119 years age early adulthood 2024 years age timedependent variable estimated using conventional stratified address familial environmental genetic confounding cox proportional hazards regressionresults 2 492 980 individuals 1 312 119 men 5263 1 180 861 women 4737 included 5867 024 ms diagnosis 20 years age median age 3150 iqr 26783754 years infectious mononucleosis childhood hazard ratio hr 198 95 ci 121323 adolescence hr 300 95 ci 248363 associated increased risk ms diagnosis remained significant controlling shared familial factors stratified cox proportional hazards regression hrs 287 95 ci 144574 319 95 ci 229446 respectively infectious mononucleosis early adulthood also associated risk subsequent ms diagnosis hr 189 95 ci 118305 risk attenuated significant controlling shared familial factors hr 151 95 ci 082276 conclusions relevance findings suggest im childhood particularly adolescence risk factor associated diagnosis ms independent shared familial factorspmid34633426 doi101001 jamanetworkopen202124932,0.0
relationship sleep quality sleeprelated biomarkers motor skill acquisition people multiple sclerosis pilot study phys ther 2021 jul 16pzab175 doi 101093 ptj pzab175 online ahead printabstractobjective neurorehabilitation involves learning new motor skills one promising clinical methods motor recovery people multiple sclerosis pwms therefore factors influence acquisition motor skills pwms need investigated sleep disturbances common pwms however study investigated effect sleep sleeprelated biomarkers skill acquisition pwms study aimed examine effect sleep sleeprelated biomarkers motor acquisition pwmsmethods forty participants ms 40 controls recruited study assess motor acquisition participant asked perform novel game virtual reality vr system 5 times blocks main outcome measures block required time complete vr game recorded errors difference scores block 5 block 1 outcomes considered represent motor skill acquisition sleep assessed selfreport using pittsburgh sleep quality index psqi objectively using sleep monitor technology serotonin level assessed using means enzymelinked immunosorbent assay elisa using plasma samplesresults significant positive correlations groups motor skill acquisition psqi score pwms significant negative correlation motor skill acquisition sleep efficiency significant positive correlation motor skill acquisition sleep latency also observed interestingly significant negative correlation observed motor skill acquisition plasma serotonin level groups correlations remained significant controlling disease severity fatigue baseline performance cognitive statusconclusions sleep quality may influence motor skill acquisition pwms circulatory serotonin level might explain relationshipimpact physical therapists encouraged aware sleep quality sleep assessment sleep management strategies considered treating pwmspmid34270772 doi101093 ptj pzab175,0.0
demyelinating disorders following covid19 vaccination n,1.0
dimethyl fumarate mitigate cognitive decline amyloidosis female appps1 mice brain res 2021 jul 4147579 doi 101016 jbrainres2021147579 online ahead printabstractintroduction alzheimers disease ad leading cause dementia major global health issue currently limited treatment options available patients one possibility expand treatment repertoire repurposing existing drugs dimethyl fumarate dmf dmf approved treatment multiple sclerosis previous animal studies suggested dmf may also beneficial effect treatment admethods used appps1 transgenic model senile amyloidosis treated female mice orally dmf two treatment paradigms pre post onset quantified learning memory parameters amyloidosis neuroinflammation determine potential dmf ad therapeuticsresults treatment dmf influence water maze performance amyloid accumulation plaque formation microglia activation recruitment immune cells brain compared vehicletreated animals oral dmf treatment halt retard disease progression micediscussion conclusion results favour use dmf treatment ad results stand contrast previous findings models emphasize importance animal model selection suggest studies elucidate mechanisms leading conflicting resultspmid34233173 doi101016 jbrainres2021147579,0.0
prophylactic antidepressants patient multiple sclerosis receiving interferonbeta prim care companion cns disord 2021 sep 30 23 5 20l02862 doi 104088 pcc20l02862no abstractpmid34592796 doi104088 pcc20l02862,0.0
outcome measures used trials gait rehabilitation multiple sclerosis systematic literature review plos one 2021 sep 30 16 9 e0257809 doi 101371 journalpone0257809 ecollection 2021abstractbackground multiple sclerosis ms associated impaired gait growing number clinical trials investigated efficacy various interventions choice outcome measures crucial determining efficiency interventions however remains unclear whether consensus outcome measures use gait intervention studies msobjective aimed identify commonly selected outcome measures randomized controlled trials rcts gait rehabilitation interventions people ms additional aims identify domains international classification functioning disability health icf studied characterize outcome measures combined adapted ms severitymethods pubmed cochrane central embase scopus databases searched rct studies gait interventions people living ms according prisma guidelinesresults 46 rcts identified 69 different outcome measures used outcome measures 6minute walking test timed go test used 37 analyzed studies followed gait spatiotemporal parameters 35 often used inform gait speed cadence step length fatigue measured 39 studies participation assessed 50 studies albeit wide variety scales 39 studies included measures covering icf levels participation measures rarely combined gait spatiotemporal parameters two studies conclusions selection outcome measures remains heterogenous rcts gait rehabilitation interventions ms however growing consensus need quantitative gait spatiotemporal parameter measures combined clinical assessments gait balance mobility rcts gait interventions ms future rcts incorporate measures fatigue measures participation domain icf provide comprehensive evaluation trial efficacy across levels functioningpmid34591875 doi101371 journalpone0257809,1.0
noncoding rnas pathogenesis multiple sclerosis front genet 2021 sep 30 12717922 doi 103389 fgene2021717922 ecollection 2021abstractmultiple sclerosis ms early onset chronic neurological condition adults characterized inflammation demyelination gliosis axonal loss central nervous system pathological cause ms complex includes genetic environmental factors nonproteincoding rnas ncrnas specifically mirnas lncrnas important regulators various biological processes past decade many studies investigated mirnas lncrnas patients ms since insightful knowledge gained field review role mirnas lncrnas ms pathogenesis discuss implications diagnosis treatmentpmid34659340 pmcpmc8514772 doi103389 fgene2021717922,1.0
manifestation susac syndrome interferon beta1a glatiramer acetate treatment misdiagnosed multiple sclerosis case report background susac syndrome ss characterized triad encephalopathy branch retinal artery occlusion sensorineural hearing loss however diagnosis ss remains difficult clinical triad rarely occurs disease onset symptom severity varies ss symptoms often suggest diseases particular multiple sclerosis ms common misdiagnosing ss ms may cause serious complications ms drugs interferon beta1a can worsen course ss case report confirms previous reports use interferon beta1a course misdiagnosed ms may lead exacerbation ss moreover case report shows glatiramer acetate may also exacerbate course ss best knowledge first reported case exacerbation ss glatiramer acetatecase presentationwe present case report patient primary diagnosis ms developed symptoms ss interferon beta1a treatment ms symptoms resolved discontinuation treatment upon initiation glatiramer acetate treatment patient developed full clinical triad ss diagnosis ms excluded glatiramer acetate therapy discontinued patients neurological state improved use combination corticosteroids intravenous immunoglobulins azathioprineconclusionsthe coincidence ss signs symptoms treatment ms first interferon beta1a glatiramer acetate suggests drugs may influence course ss case report indicates treatment glatiramer acetate may modulate even exacerbate course ss,0.0
prevalence myocardial infarction among multiple sclerosis patients systematic review metaanalysis abstractbackgroundpeople multiple sclerosis pwms suggested higher death rate compared overall population increased risk incidence cardiovascular diseases possible contributing factor patients suggested prone early death due myocardial infarction mi aimthis systematic review aims describe prevalence mi among ms patients comparison nonms populationmethodwe thoroughly searched publications reporting prevalence mi among ms patients pubmed scopus embase web science excluded studies focusing following conditions ischemic heart disease autopsy ms patients ms patients previous history cardiovascular diseases ms diagnosed mi moreover excluded reviews editorials commentaries used random effect model calculate pooled prevalenceresultswe included nineteen studies comprising 44 66616 participants overall prevalence mi 17 among pwms pooled odds ratio estimate mi 141 msfree populationconclusionsresults systematic review confirms increased risk mi among ms cases consequently cardiovascular diseases considered management patients,0.0
role expectations futureoriented cognitions quality life people multiple sclerosis systematic review abstractpurposemultiple sclerosis ms highly variable condition characterised uncertainty disease course can make formation expectations future difficult systematic review aimed examine associations expectations future oriented cognitions focs quality life qol people ms pwms methodsfollowing prisma guidelines literature october 2019 searched using medline embase psycinfo web science quantitative studies investigated relationships foc qol pwms assessed using standardised qol assessment considered inclusion data extraction results analysed using narrative synthesis focusing valence focs positive negative unvalenced quality appraisal conducted using mixed methods appraisal tool mmat stages review patientled person msresultsa total 13 studies met review inclusion criteria combined sample size 4 179 studies 11 involved measures positive focs commonly selfefficacy one measured negative foc one foc unclassified nine studies found significant associations qol selfefficacy although positively valenced constructs less frequently reported significant associations higher qol also evidencedconclusionsidentifying ways foster positive focs particularly selfefficacy may beneficial effects qol research needed understand impacts negative focs qol determine whether processes meaningfully targeted interventions,0.0
antigenspecific tolerization human autoimmunity inhibition interferonbeta1a antidrug antibodies multiple sclerosis case report abstractbackground antigenspecific tolerance autoimmune diseases goal effective treatment minimal sideeffects whilst achievable animal models notably via intravenous delivery modelspecific autoantigen following transient cd4 t cell depletion specific multiple sclerosis autoantigens remainunproven however antidrug antibodies human therapeutic proteins represent model human autoimmune condition may used examine immunetolerance induction people ms pwms interferonbeta1a ifn1a develop neutralizing antibodies ifn1a disappear repeated tests yearsmethods one pwms recruited part planned phase iia trial n15 developed neutralizing antibodies subcutaneous ifn1a mitoxantrone 12mg m2 administered lymphocyte depleting agent followed four days 88g day+three 132g day intravenous ifn1a subcutaneous ifn1a three times week maintained followup ifn1a neutralizing antibody responses serum measured treatment threemonthly 12 monthsfindings one participant recruited within 6 months tolerization neutralizing antibodies undetectable tolerization treatment well tolerated however study terminated first enrolment ethical grounds treatment alternatives became available potential risks mitoxantrone use increasedinterpretation data suggest may possible induce antigenspecific tolerance providing tolerogenic antigen following transient immune depletion studies warrantedfunding study supported unrestricted research grant merckserono,0.0
50 yearold woman delayed diagnosis neuromyelitis optica spectrum disorder clinical course serial neuroimaging findings acta neurol taiwan 2021 sep 30 30 3 108112abstractpurpose neuromyelitis optica nmo spectrum disorder multiple sclerosis ms similar clinical presentations may make diagnostic difficulty especially data aquaporin4 aqp4 antibody available reported diagnostic therapeutic dilemma woman delayed diagnosis nmo spectrum disorder 20 yearscase report patient 51 years old woman suffered several episodes relapsing remission limbs weakness visual impairment gait disturbance since 29 years old diagnosed case ms received treatment accordingly treatment use rebif started since 20082012 shifted fingolimod due several minor attacks still noted period serum aqp4igg checked use fingolimod using enzymelinked immunosorbent assay elisa result showed seronegative ab however occasional minor attacks still noted may 2018 severe relapsing developed brain magnetic resonance imaging mri showed marked progression brain lesion initially progressive multifocal leukoencephalopathy suspected cerebrospinal fluid serologic study john cunningham virus jcv negative aqp4igg rechecked using cellbased assay cba result showed positive finding thereafter therapy changed nmo spectrum disorder regimenconclusion worthwhile recheck serum aqp4igg initial study showed negative result using elisa since cba higher sensitivity previous study methodpmid34841506,0.0
utility telemedicine pediatric rheumatology covid19 pandemic background covid19 pandemic telemedicine provided alternative inperson visits patients practicing social distancing undergoing quarantine time rapid expansion telemedicine implementation various clinical specialties settings observational study aim examine utility telemedicine pediatric rheumatology clinic 3 months covid19 pandemicmethodsa review outpatient pediatric rheumatology telemedicine encounters conducted apriljune 2020 telemedicine visits n 75 compared patients seen practice prior year officebased visits march 2019march 2020 n 415 patient characteristics information noshow visits completed visits new patient followup status new patients received visit within 2 weeks calling schedule appointment analyzed chart review independent sample ttest chi square statistic used determine statical significance two groups twoproportion ztest used compare visit metricsresultsthe percentage new patients utilizing telemedicine 60 lower statistically significant compared percentage new patient office visits 84 previous year p 00001 change noshow rate groups patient characteristics similarconclusionsthis study demonstrates statistically significant decrease new patient visits pandemic telemedicineonly appointments compared inoffice visits previous year suggests possible hesitation seek care time however significant difference among patient characteristics telemedicine visits pandemic inoffice visits previous year experience patient visits able conducted via telemedicine limited physical exam using caregivers help pandemic however studies will need ascertain patient satisfaction preference telemedicine future,0.0
neurofeedback therapy management multiple sclerosis symptoms current knowledge future perspectives j integr neurosci 2021 sep 30 20 3 745754 doi 1031083 jjin2003079abstractfatigue frequent debilitating symptom patients multiple sclerosis ms affective manifestations also high prevalence population can drastically impact patients functioning considerable proportion patients ms suffer cognitive deficits affecting general social cognitive domains addition pain ms commonly observed neurology wards different types may result exacerbated ms comorbidities complaints tend cluster together patients seem complex pathophysiology challenging management exploring effects new interventions improve outcomes ameliorate patients quality life neurofeedback nfb might place context enhancing reducing activity regions specific electroencephalographic bands ie theta alpha beta sensorimotor rhythm work briefly revisits principles nfb application published data scarce heterogeneous yet suggest preliminary evidence potential utility nfb patients ms ie depression fatigue cognitive deficits pain nfb simple adapt easy coach place management ms symptoms merits investigations comparing different nfb protocols ie cortical target specific rhythm session duration number performing comprehensive evaluation help developing optimizing interventions targeting specific symptoms aspects also open way association technique approaches ie brain stimulation cognitive rehabilitation exercise training psychotherapies proved worth ms domainspmid34645108 doi1031083 jjin2003079,0.0
machine learning techniques personalised medicine approaches immunemediated chronic inflammatory diseases applications challenges front pharmacol 2021 sep 30 12720694 doi 103389 fphar2021720694 ecollection 2021abstractin past decade emergence machine learning ml applications led significant advances towards implementation personalised medicine approaches improved health care due exceptional performance ml models utilising complex big data immunemediated chronic inflammatory diseases group complex disorders associated dysregulated immune responses resulting inflammation affecting various organs systems heterogeneous nature diseases poses great challenges tailored disease management addressing unmet patient needs applying novel ml techniques clinical study chronic inflammatory diseases shows promising results great potential precision medicine applications clinical research practice review highlight clinical applications various ml techniques prediction diagnosis prognosis autoimmune rheumatic diseases inflammatory bowel disease autoimmune chronic kidney disease multiple sclerosis well ml applications patient stratification treatment selection highlight use ml drug development including target identification validation drug repurposing well challenges related data interpretation validation ethical concerns related use artificial intelligence clinical researchpmid34658859 pmcpmc8514674 doi103389 fphar2021720694,0.0
comparing underlying mechanisms depression multiple sclerosis rheumatoid arthritis j integr neurosci 2021 sep 30 20 3 765776 doi 1031083 jjin2003081abstractmultiple sclerosis ms rheumatoid arthritis ra common chronic autoimmune diseases affecting many people worldwide clinically different phenotype diseases thought autoimmunemediated origin ms ra share genetic similarities diseases antibodies host antigens can found aside wellknown somatic symptoms many ra patients also show signs symptoms psychiatric illnesses depression common diagnosis commentary diseases will introduced briefly characterized individually compared depression will introduced one frequent psychiatric diseases general population paper focuses presenting possible causes including psychosocial factors genetics immunologic mechanisms hypotheses aimed explain higher incidence depression two seemingly different autoimmune diseases will discussedpmid34645110 doi1031083 jjin2003081,0.0
methylprednisolone stimulated gene expression gilz mcl1 basal cortisol levels multiple sclerosis patients relapse associated clinical response sci rep 2021 sep 30 11 1 19462 doi 101038 s4159802198868yabstractglucocorticoids gcs main treatment relapse multiple sclerosis ms decreased sensitivity gcs ms patients associated lack suppressive effect gcs inflammatory molecules well increased resistance apoptosis investigated gcsensitivity measuring effect intravenous methylprednisolone ivmp treatment transactivation antiinflammatory apoptotic genes gilz mcl1 noxa respectively accordance clinical outcome thirty nine ms patients studied 15 clinically isolated syndrome cis 12 relapsing remitting rrms 12 secondary progressive spms relapse patients underwent treatment ivmp 5 days blood drawn ivmp treatment day 1 1 h ivmp treatment days 1 5 gilz mcl1 noxa determined qpcr expanded disability status evaluated patients divided according clinical response ivmp gilz mcl1 gene expression significantly higher following first ivmp treatment responders compared nonresponders furthermore serum basal cortisol 1 25oh vitamin d levels significantly higher clinicalresponders compared nonclinical responders findings suggest differential gilz mcl1 gene expression clinicalresponders nonclinical responders may implicate importance gilz mcl1 possible markers predicting glucocorticoid sensitivity response gctherapy ms patients following first ivmp injectionpmid34593869 doi101038 s4159802198868y,0.0
internet resources align exercise training physical activity guidelines people multiple sclerosis mult scler j exp transl clin 2021 sep 30 7 3 20552173211038035 doi 101177 20552173211038035 ecollection 2021 julsepabstractbackground exercise training lifestyle physical activity identified evidencebased approaches improving symptoms quality life among persons multiple sclerosis ms evidence supported development physical activity guidelines pags people ms goal guidelines involved broad dissemination uptake substantial evidence low rates participation exercise training physical activity populationobjective current study evaluated quality consistency information webpages physical activity established pags people msmethod search conducted september 2020 using google search engine webpages containing physical activity information people ms evaluated webpages list 18 guidelines adults ms based recommendations three resourcesresults search yielded 157 webpages 27 met inclusion criteria average webpages accurately addressed 5 18 guidelines commonly addressed guidelines involved msspecific symptom identification n 26 example modalities aerobic n 20 strength n 16 trainingconclusion many online recourses regarding physical activity exercise training ms either inconsistent established pags address guidelinespmid34616564 pmcpmc8488526 doi101177 20552173211038035,0.0
outcome covid19 infection multiple sclerosis patients receiving diseasemodifying therapies j res med sci 2021 sep 30 2685 doi 104103 jrmsjrms_1047_20 ecollection 2021abstractbackground spread covid19 treatment diseases multiple sclerosis ms resumed caution due diseasemodifying therapies dmts used subset patients immunoregulatory effects drugs aim assess outcome covid19 infection ms patients receiving dmtsmaterials methods crosssectional study involving 45 covid19infected patients previously diagnosed ms data regarding ms status type dmt taken patients extracted isfahan ms institute registry summarized diagnosis ms based 2017 mcdonald criteria diagnosis covid19 based computed tomography scan polymerase chain reaction nasopharyngeal swabsresults 45 ms patients infected covid19 5 unfavorable outcomes two patients deceased three persistent respiratory complications 4week followup visit hypertension diabetes seizures rheumatoid arthritis among comorbidities patients reported patients died received rituximab part ms treatment patients recovered completelyconclusion different drug category may possess distinct risk infection therefore robust evidence available safest drug utilized therapy postponed possible minimize patient risk diseasemodifying therapy use ms patients cautiously applied effect covid19 infection prognosis yet studiedpmid34760002 pmcpmc8548892 doi104103 jrmsjrms_1047_20,0.0
interventions increase leukocyte testing treatment dimethyl fumarate int j environ res public health 2021 sep 30 18 19 10312 doi 103390 ijerph181910312abstractdimethyl fumarate dmf treatment multiple sclerosis may cause leukopenia infection accordingly periodic white blood cell wbc monitoring recommended sought evaluate us department veteran affairs safety program provides facilities list patients prescribed dmf therapy without documented white blood cell count wbc identified 118 sites patients treated dmf 1 january 2016 30 september 2016 site asked seven interventions used improve wbc monitoring academic detailing provider education without academic detailing electronic clinical reminders request provider action plan draft orders wbc monitoring patient mailings patient calls survey response rate 78 92 responding sites 78 included sites 1115 patients mean rate wbc monitoring 54 multivariate analysis academic detailing increased rate 17 95 ci 4 30 p 0011 provider education increased rate 9 95 ci 06 18 p 0037 wbc monitoring rate increased 38 additional intervention used 95 ci 1264 p 0005 interventions focused physician including academic detailing associated improved wbc monitoring patients risk leukopenia dmf treatmentpmid34639610 doi103390 ijerph181910312,0.0
dietary insights neurological diseases curr neurol neurosci rep 2021 sep 29 21 10 55 doi 101007 s1191002101143wabstractpurpose review dietary interventions may play role pathophysiology common neurological disorders alzheimers disease parkinsons disease stroke migraines multiple sclerosis epilepsy article describes common impactful dietary regimens commonly encountered neurological disordersrecent findings plantbased lowfat highfiber diets rich antioxidants lifestyle interventions may reduce burden disability common neurological disorders ketogenic diet diet choice treatment refractory epilepsy example diverse neurological disorders demonstrate several common pathophysiological mechanisms including increased oxidative stress neuroinflammation disrupted metabolism dietary interventions can potentially influence pathophysiological processes thus favorably alter clinical outcomes adequate dietary choices considered part continuum healthy lifestyle choicespmid34586517 doi101007 s1191002101143w,0.0
effectiveness interventions prevent falls people multiple sclerosis parkinsons disease stroke umbrella review background implementation conditionspecific falls prevention interventions proving challenging due lack critical mass resources given similarities falls risk factors across stroke parkinsons disease pd multiple sclerosis ms development intervention designed groups comprising people three neurological conditions may provide pragmatic solution challenges aims umbrella review investigate effectiveness falls prevention interventions ms pd stroke identify commonalities differences effective interventions condition inform development intervention mixed neurological groupsmethodsa systematic literature search conducted using 15 electronic databases grey literature searches handscreening reference lists systematic reviews studies investigating effects falls prevention interventions ms pd stroke included methodological quality reviews assessed using measurement tool assess systematic reviews 2 matrix evidence table used assess degree overlap grading recommendations assessments development evaluation framework used rate quality evidence findings presented narrative synthesis summary evidence tableresultseighteen reviews included three investigating effectiveness falls prevention interventions ms 11 pd three stroke one pd stroke exercisebased interventions commonly investigated three conditions differences identified content delivery interventions low moderate quality evidence found effectiveness exercisebased interventions reducing falls pd best available evidence suggests exercise effective reducing falls stroke evidence effect identified msconclusionsthe findings suggest exercisebased interventions effective reducing falls pd however evidence ms stroke less conclusive strong theoretical rationale remains use exercisebased interventions address modifiable physiological falls risk factors people ms pd stroke supporting feasibility mixeddiagnosis intervention given high overlap low methodological quality primary studies focus development highquality trials investigating effectiveness falls prevention interventions rather publication systematic reviews,0.0
scoping review minimum foot clearance exploration levelground clearance individuals abnormal gait int j environ res public health 2021 sep 29 18 19 10289 doi 103390 ijerph181910289abstractbackground falls major health concern one three adults age 65 falling year key gait parameter indicative tripping minimum foot clearance mfc occurs midswing phase gait second twopart scoping review mfc literature aim paper identify vulnerable populations conditions impact mfc mean median relative controls information will inform future design maintenance standards outdoor built environment guidelines methods four electronic databases searched identify journal articles conference papers report levelground mfc characteristics two independent reviewers screened papers inclusion results 1571 papers 43 relevant papers included review twentyeight conditions studied effects mfc eleven 28 conditions led decrease mean median mfc including dualtask walking older adults fallers multiple sclerosis treadmill walking studies conducted indoors conclusions lack standardized research methods covariates gait speed made difficult compare mfc values studies purpose defining design maintenance standards outdoor built environment standardized methods defining mfc emphasis outdoor trials needed future studiespmid34639597 doi103390 ijerph181910289,0.0
interferon beta treatment multiple sclerosis campania region italy merging reallife routinely collected healthcare data plos one 2021 sep 29 16 9 e0258017 doi 101371 journalpone0258017 ecollection 2021abstractbackground aim overcome limitations previous clinical populationbased studies merging clinical registry routinelycollected healthcare data specifically describe differences clinical outcomes healthcare resource utilization costs interferon beta formulations multiple sclerosis ms methods included 850 patients ms treated interferon beta formulations 2015 2019 seen ms clinical care research centre federico ii university naples italy linkage routinelycollected healthcare data prescription data hospital admissions outpatient services extracted computed clinical outcomes relapses 6month edss progression using roving edss reference persistence time spent specific interferon beta formulation adherence medication possession ratio mpr healthcare resource utilization costs annualized hospitalization rate ahr costs hospital admissions dmts evaluate differences interferon beta formulations used linear regression adherence poisson regression ahr mixedeffect regression costs coxregression models time varying variables covariates age sex treatment duration baseline edss adherenceresults looking clinical outcomes rates relapses edss progression lower studies run previous cohorts differences relapse risk interferon beta formulations risk discontinuation higher betaferon extavia hr 328 95ci 211 512 p001 adherence lower betaferon extavia coeff 005 95ci 010 001 p 002 avonex coeff 006 95ci 011 002 p001 compared rebif plegridy coeff 008 95ci 001 016 p 002 ahr costs ms hospital admissions higher betaferon extavia irr 238 95ci 101 555 p 004 coeff 1495 95ci 139 2851 p 003 conclusions showed feasibility merging routinelycollected healthcare data clinical registry future ms research confirmed interferon beta formulations play important role management ms positive clinical outcomes differences interferon beta formulations mostly driven adherence healthcare resource utilizationpmid34587188 doi101371 journalpone0258017,0.0
challenges treatment renal echinococcosis gross hydatiduria unsalvageable kidney case report abstractintroductionrenal echinococcosis rare occurrence although often asymptomatic can present various mild drastic presentations hydatiduria pathognomonic diagnosis can preliminarily established imaging treatment primarily surgical present patient renal echinococcosis treated successfully exclusive antiparasitic pharmacotherapy refusing surgery despite extensive renal involvement hope report help establish future solid guidelines regarding uncommon therapeutic approachcase presentationthis case 49yearold syrian shepherd presenting flank pain passage grapeskinlike structures urine diagnosis renal echinococcosis hydatiduria significant parenchymal destruction established based exposure history positive serology imaging findings renal scintigraphy proper counseling patient refused nephrectomy therefore started dual pharmacotherapy albendazole praziquantel uneventful followup satisfactory response treatmentconclusionthis case embodies daily challenges physicians navigate uphold ethical principles practice support patients autonomy delivering best standards care consulting scientific evidence although surgery cornerstone renal echinococcosis treatment treating physicians prepared tackle situations surgery done offer best next available option patients refuse surgery data exclusive pharmacotherapy limited future research thoroughly investigate efficacy uncommon approach outline reliable recommendations facilitating future clinical decisionmaking avenue,0.0
csf levels cxcl12 osteopontin early markers primary progressive multiple sclerosis neurol neuroimmunol neuroinflamm 2021 sep 29 8 6 e1083 doi 101212 nxi0000000000001083 print 2021 novabstractbackground objectives evaluate extent intrathecal inflammation patients primary progressive ms ppms time diagnosis define markers specific inflammatory profile capable distinguishing progressive relapsingremitting multiple sclerosis rrms methods levels 34 pro antiinflammatory cytokines chemokines csf evaluated diagnosis 16 patients ppms 80 rrms patients underwent clinical evaluation including expanded disability status scale assessment 3t brain mri detect white matter cortical lesion number volume global regional cortical thicknessresults higher levels cxcl12 odds ratio 397 95 ci 134117 monocyterelated osteopontin 224 95 ci 101499 detected patients ppms whereas levels interleukin10 il10 028 95 ci 009096 significantly increased rrms high cxcl12 levels detected patients increased gray matter lesion number volume p 0001 r 0832 r 0821 respectively pathway analysis confirmed chronic inflammatory processes occurring ppmsconclusions time diagnosis specific csf protein profile can recognize presence early intrathecal inflammatory processes possibly stratifying ppms respect rrms elevated csf levels cxcl12 osteopontin suggested key role brain innate immunity glia activity ms molecules represent useful candidate markers ms progression implications pathogenesis treatment progressive msclassification evidence study provides class iii evidence cxcl12 monocyterelated osteopontin may correlated ppms il10 may related rrms may correlated due bonferroni correction negating statistical correlations found studypmid34588298 doi101212 nxi0000000000001083,0.0
brainstem syndrome onset related early ms diagnosis peru national referral center cohort heliyon 2021 sep 29 7 10 e08069 doi 101016 jheliyon2021e08069 ecollection 2021 octabstractbackground ms unpredictable regarding clinical symptoms however certain symptoms represent preferred localization white matter lesions brainstem spinal cord optic nerveobjectives investigate epidemiological clinical imaging characteristics ms patients national referral center peru evaluate whether type symptom onset relates time making ms diagnosismethods retrospective study ms patients instituto nacional de ciencias neurolgicas january 2010 december 2018 four different syndromes selected analysis symptom onset optic neuritis brainstem syndrome myelitis others results identified 268 patients diagnosis ms given excluding misdiagnosed patients 33 neuromyelitis optica lost incomplete records 121 patients included majority patients 466 born lima female male ratio 137 1 mean age diagnosis 31 years onset myelitis present 35 rrms patients followed brainstem syndrome 25 optic neuritis 18 brainstem syndrome statistically significant predictor earlier diagnosis adjusted hr 209 p 0015 conclusion brainstem syndrome initial presentation ms peru related earlier diagnosispmid34765756 pmcpmc8569397 doi101016 jheliyon2021e08069,0.0
human induced pluripotent stem cellderived tdp43 mutant neurons exhibit consistent functional phenotypes across multiple gene edited lines despite transcriptomic splicing discrepancies front cell dev biol 2021 sep 29 9728707 doi 103389 fcell2021728707 ecollection 2021abstractgene editing technologies hold great potential enhance ability model inheritable neurodegenerative diseases specifically engineering multiple amyotrophic lateral sclerosis als mutations isogenic cell populations facilitates determination whether different causal mutations cause pathology via shared mechanisms provides capacity separate mechanisms genotypespecific effects geneedited cellbased models human disease become commonplace urgent need verify models constitute consistent accurate representations native biology commercially sourced induced pluripotent stem cellderived motor neurons cellular dynamics international edited express alsrelevant mutations tdp43m337v tdp43q331k compared inhouse derived lines engineered express tdp43q331k mutation within wtc11 background results highlight electrophysiological mitochondrial deficits edited cells correlate patientderived cells suggesting consistent cellular phenotype arising tdp43 mutation however significant differences transcriptomic profiles splicing behavior edited cells underscores need careful comparison multiple lines attempting use cells means better understand onset progression als humanspmid34660586 pmcpmc8511491 doi103389 fcell2021728707,0.0
cuatsm improves motor function extends survival tolerated high dose sod1g93a mice c57bl#x2f 6 background sci rep 2021 sep 29 11 1 19392 doi 101038 s4159802198317wabstractthe synthetic coppercontaining compound cuatsm emerged one promising drug candidates developed treatment amyotrophic lateral sclerosis als multiple studies reported cuatsm treatment provides therapeutic efficacy various mouse models als without observable adverse effects moreover recent results open label clinical study suggested daily oral dosing cuatsm slows disease progression patients sporadic familial als providing encouraging support cuatsm treatment als assessed cuatsm high copy sod1g93a mice congenic c57bl 6 background treating 100 mg kg day gavage starting 70 days age dose specific model assessed previously unexpectedly report subset mice initially administered cuatsm exhibited signs clinical toxicity necessitated euthanasia extremis 351 days treatment following 1week washout period remaining mice resumed treatment reduced dose 60 mg kg day revised dose treatment cuatsm slowed disease progression increased survival relative vehicletreated littermates work provides first evidence cuatsm produces positive diseasemodifying outcomes high copy sod1g93a mice congenic c57bl 6 background furthermore results 100 mg kg day phase study support dose escalation determination tolerability prudent step assessing treatments previously unassessed models genetic backgroundspmid34588483 doi101038 s4159802198317w,1.0
caregiver burden associated factors among primary caregivers patients als home care crosssectional survey study bmj open 2021 sep 28 11 9 e050185 doi 101136 bmjopen2021050185abstractobjectives study aims understand caregiver burden experienced primary caregivers patients amyotrophic lateral sclerosis als explore factors influencing caregiver burdendesign crosssectional survey design usedsetting study conducted als inpatients followup outpatients neurology department tertiary general hospital taiyuan shanxi china caregiversparticipants patients als caregivers n120 pairs participated facetoface interviewprimary secondary outcome measures primary outcome measures included zarit burden interview scores personal role burden scores secondary outcomesresults multiple linear logistic regression analyses performed examine factors influencing burden als patients caregivers multiple linear regression showed caregivers higher anxiety index ai experienced greater personal 0089 p0001 role 0065 p0001 overall 0200 p0001 burden logistic regression analysis showed ai p0025 1351 95 ci 1038 1759 disease knowledge level p0033 0305 95 ci 0107 0593 influencing factors als load classificationconclusions higher ai scores associated greater caregiver burden caregiver burden caregivers knowledge patients disease 0305 times good knowledge level disease knowledge ai score can serve key predictors caregiver burden alspmid34588253 doi101136 bmjopen2021050185,0.0
association chiropractors view practice patient encounterlevel characteristics ontario canada crosssectional study background chiropractors diverse views practice impact patient profiles treatment approaches remains unclear assessed association chiropractors view practice unorthodox versus orthodox patient encounterlevel characteristics among chiropractors practice ontario canadamethodswe conducted crosssectional study using ontario chiropractic observation analysis study ocoast data ocoast ontario chiropractors randomly recruited list registered chiropractors 2015 recorded 100 consecutive patient encounters classified chiropractors response regarding views practice unorthodox viewing vertebral subluxation encumbrance health corrected benefit overall wellbeing views considered orthodox patient encounterlevel characteristics included 1 nonmusculoskeletal reasonforencounter 2 subluxation diagnosis 3 duration encounter logtransformed modeling 4 unimodal manipulative treatment 5 patient health characteristics good health status activity limitations conducted multilevel logistic regression assess association view practice aforementioned characteristics accounting potential confounders clustering encounters within chiropractors multilevel models two levels level 1patient encounter level level 2chiropractor level level 1 patient encounters nested within level 2 chiropractorsresultswe included 40 chiropractors mean age 434 years sd 115 3 378 chiropractorpatient encounters 2 332 unique patients identified mean age 485 years sd 185 chiropractors unorthodox views higher odds patients nonmusculoskeletal reasonforencounter adjusted odds ratio aor 165 95 ci 32840 subluxation diagnosis aor 630 95 ci 429491 encounters chiropractors unorthodox views 06 times shorter orthodox views 95 ci 0409 chiropractor level explained 32 75 49 variability nonmusculoskeletal reasonforencounter subluxation diagnosis encounter duration respectively observed association unorthodox view unimodal manipulative treatment patient health characteristicsconclusionschiropractors unorthodox view practice associated treating nonmusculoskeletal conditions subluxation diagnosis shorter duration encounter chiropractor level explained high proportion variability outcomes findings implications understanding chiropractic practice informing interprofessional collaboration,0.0
aquaporin4 autoantibody detection elisa retrospective characterization commonly used assay mult scler int 2021 sep 28 20218692328 doi 101155 2021 8692328 ecollection 2021abstractobjective aquaporin4 aqp4 serum autoantibodies detected variety methods highest sensitivity achieved cellbased assays enzymelinked immunosorbent assay elisa still commonly utilized clinicians worldwidemethods performed retrospective review identify patients university utah aqp4 elisa testing arup laboratories 2010 2017 reviewed diagnostic evaluation final diagnosis based elisa titer resultresults total 750 tests aqp4 elisa analyzed 47 unique patients positive titers identified less half patients 49 met clinical criteria neuromyelitis optica spectrum disorder nmosd cases low positive titers 3079 u ml n 19 common final diagnosis multiple sclerosis 526 moderate positive cohort 80799 u ml n 14 little half cohort 643 nmosd cases high positives 80160 u ml n 14 100 patients met clinical criteria nmosdconclusions data illustrates diagnostic uncertainty associated aqp4 elisa assay still commonly ordered clinicians despite availability sensitive specific tests detect aqp4 autoantibodies patients suspected nmosd particular low positive titer aqp4 elisa results particularly nonspecific diagnosis nmosd importance accessibility sensitive specific aqp4 testing overemphasized clinical practicepmid34621549 pmcpmc8492278 doi101155 2021 8692328,0.0
genomewide association study identifies 2 new loci associated antinmdar encephalitis neurol neuroimmunol neuroinflamm 2021 sep 28 8 6 e1085 doi 101212 nxi0000000000001085 print 2021 novabstractbackground objectives investigate genetic determinants common type antibodymediated autoimmune encephalitis antinmda receptor antinmdar encephalitismethods performed genomewide association study 178 patients antinmdar encephalitis 590 healthy controls followed colocalization analysis identify putatively causal genesresults identified 2 independent risk loci harboring genomewide significant variants p 5 108 22 1 chromosome 15 harboring lrrk1 gene 1 chromosome 11 centered acp2 nr1h3 genes larger region high linkage disequilibrium colocalization signals expression quantitative trait loci different brain regions immune cell types suggested acp2 nr1h3 madd ddb2 c11orf49 putatively causal genes best candidate genes region lrrk1 encoding leucinerich repeat kinase 1 protein involved bcell development nr1h3 liver x receptor alpha transcription factor whose activation inhibits inflammatory processesdiscussion study provides evidence relevant genetic determinants antibodymediated autoimmune encephalitides outside human leukocyte antigen hla region results suggest future studies larger sample sizes will successfully identify additional genetic determinants contribute elucidation pathomechanismpmid34584012 doi101212 nxi0000000000001085,0.0
multiparametric mri analysis evaluation renal function patients hyperuricemia preliminary study background investigate renal dysfunction patients hyperuricemia employing multiparametric mri protocol consisting quantitative water molecule diffusion microstructure microscopic perfusion oxygenation measurements kidneysmaterials methodsa total 48 patients hyperuricemia hu 22 agematched healthy control subjects hc enrolled study participant three different functional magnetic resonance imaging fmri sequences acquired analyzed including intravoxel incoherent motion imaging ivim diffusion tensor imaging dti bloodoxygenleveldependent mri bold thereafter independent twosample ttest applied discover significant differences mri indices hyperuricemia hu hc groups specific potential biomarkers two subgroups hu group asymptomatic hyperuricemia group ah gouty arthritis group ga multivariate logistic regression analyses performed classify ah ga group using mri indices significant betweengroup differences receiver operating characteristic roc curve plotted area roc curve auc calculated assess performance mr index differentiation ah ga groupsresultsten parametric values hu group significantly lower hc group among 14 fmri parameters p 005 cortical d d f values medullary d r2values significant differences ah ga groups p 005 combining cortical d f values medullary r2 value gave best diagnostic efficacy yielding auc sensitivity specificity 0967 0022 9167 9583 respectivelyconclusionsa multiparametric mr analysis plays important role evaluation renal dysfunction hyperuricemia multiple perspectives promising method noninvasive detection identification earlystage renal damage induced hyperuricemia,0.0
contribution rare variant associations neurodegenerative disease presentation npj genom med 2021 sep 28 6 1 80 doi 101038 s41525021002433abstractgenetic factors contribute neurodegenerative diseases high heritability estimates across diagnoses however large portion genetic influence remains poorly understood many previous studies attempted fill gaps performing linkage analyses association studies individual disease cohorts failed consider clinical pathological overlap observed across neurodegenerative diseases potential genetic overlap phenotypes leveraged rare variant association analyses rvaas elucidate genetic overlap among multiple neurodegenerative diagnoses including alzheimers disease amyotrophic lateral sclerosis frontotemporal dementia ftd mild cognitive impairment parkinsons disease pd well cerebrovascular disease using data generated customdesigned neurodegenerative disease gene panel ontario neurodegenerative disease research initiative ondri expected 3 ondri participants harboured monogenic variant likely driving disease presentation yet genes binned based previous disease associations observed enrichment putative loss function variants pd genes across ondri cohorts individual genebased rvaa identified significant enrichment rare nonsynonymous variants park2 ftd cohort notch3 pd cohort results indicate may greater heterogeneity genetic factors contributing neurodegeneration previously appreciated although mechanisms genes contribute disease presentation must explored hypothesize may result rare variants moderate phenotypic effect contributing overlapping pathology clinical features observed across neurodegenerative diagnosespmid34584092 doi101038 s41525021002433,0.0
patients high risk severe clinical course covid19 smallarea data support vaccination populationbased interventions germany background research shown risk severe course covid19 increased elderly population among patients chronic conditions aim study provide estimates size vulnerable populations high risk severe covid19 course germany based currently available risk factor datamethodswe used nationwide outpatient claims data years 2010 2019 collected according 295 code social law v covering data statutory health insurees shi nearly 87 entire german population considered 15 chronic disorders based current state knowledge clinically relevant risk factors three risk groups severe covid19 course defined 1 individuals age group 15 59 years least two comorbid disorders 2 individuals aged 60 79 years least one disorder 3 individuals 80 years older irrespective presence chronic conditions regional analysis conducted level administrative districts n 401 resultsoverall 26 individuals 15 years high risk severe covid19 course 2019 amounting total number nearly 185 million individuals germany included 38 million individuals risk group 1 92 million risk group 2 54 million risk group 3 corresponding 8 50 100 german inhabitants respective age groups level 17 administrative regions formed association shi physicians aship regions proportion individuals high risk ranged 21 hamburg 35 saxonyanhalt smallarea estimates varied 18 freiburg badenwrttemberg 39 district elbeelster brandenburg conclusionsthe present study provides smallarea estimates populations high risk severe covid19 course data particular importance planning preventive measures vaccinationtrial registrationnot applicable,0.0
diagnostic significance magnetic resonance imaging distinguishing temporomandibular disorders retrospective chart review background study evaluate diagnostic significance magnetic resonance imaging mri distinguishing temporomandibular disorders tmd methodsa total 684 patients tmd included study diagnosis tmd conducted according international criteria two professional radiologists selected professional training kappa values compared diagnosis results determine consistency diagnosis mri images 684 patients analyzed diagnosis results obtainedresultsmri can used diagnosis tmd significantly females 518 cases males 166 cases tmd disc displacement without reduction common youth group majority aged 2030 years highest incidence temporomandibular joint osteoarthrosis 60yearold age group followed 70yearold age groupconclusionsbilateral temporomandibular joint mri can clearly show changes significantly female tmd male osteoarthritis significant correlation age,0.0
association age contrastenhancing lesions across multiple sclerosis disease spectrum neurology 2021 aug 10101212 wnl0000000000012603 doi 101212 wnl0000000000012603 online ahead printabstractobjective investigate association age presence contrast enhancing lesions cels cranial mri scans different disease courses multiple sclerosis ms describe frequency cels function age four large randomized controlled trial rct datasetsmethods using original trial data combirx clinicaltrialsgov identifier nct00211887 trial relapsingremitting ms ascend nct01416181 trial secondary progressive ms two primary progressive ms trials promise informs nct00731692 describe occurrence cels per age group baseline entire trial cohort one year followup treatment armsresults combirx included 1 008 ascend 889 promise 943 informs 970 participants baseline cel frequency differed datasets according disease courses 396 combirx 239 ascend 140 promise 123 informs participants cels distribution disease course largely preserved within age group datasets almost linear decrease percentage participants cels advancing age one year experimental treatment cel occurrence reduced trial datasets almost absent ascend decrease cel occurrence advancing age preserved combirx promise informs one year treatment investigated association baseline factors age disease duration sex edss cels baseline multivariable binary logistic regression models age characteristic associated risk cels baseline datasets higher age associated lower risk cels odds ratios cels baseline per year increase age combirx 096 95 confidence interval ci 095 098 ascend 094 95 ci 092 097 promise 094 95 ci 091 096 informs 097 95 ci 094 099 conclusions analysis four large wellcharacterized rct datasets shows association age cel occurrence general phenomenon across spectrum ms disease courses findings replicated real world ms datasetspmid34376508 doi101212 wnl0000000000012603,0.0
homocysteine predictor tool multiple sclerosis discoveries craiova 2021 sep 28 9 3 e135 doi 1015190 d202114 ecollection 2021 julsepabstractmultiple sclerosis ms progressive irreversible disease affects central nervous system cns still unknown etiology study aimes establish homocysteine pattern can predict ms diseases progression identify potential disease progression marker can easy perform noninvasive order predict diseases outcome order achieve goal included 10 adult rrms subjects 10 adult spms subjects 10 agematched healthy subjects homocysteine plasma level measured using automated latex enhanced immunoassay cobalamin folate measurements performed using automated chemiluminescence immunoassay clia hcr calculated dividing homocysteine plasma level cobalamin plasma level found homocysteine level plasma rrms patients spms group significantly increased compared control group significantly higher concentration homocysteine spms group compared rrms group addition hcr significantly increased spms compared rrms group good index disease severitypmid34816003 pmcpmc8601869 doi1015190 d202114,0.0
gut environment multiple sclerosis rinsho shinkeigaku 2021 aug 26 doi 105692 clinicalneurolcn001590 online ahead printabstractmultiple sclerosis ms inflammatory demyelinating disease central nervous system cns t cellmediated autoimmune processes assumed involved pathogenesis recently accumulating evidence indicated commensal bacteria interact host immune system alteration commensal bacteria composition termed dysbiosis associated various autoimmune diseases including cns autoimmune diseases effect gut microbiota disease initially shown experimental autoimmune encephalomyelitis eae animal model ms recent analysis microbiota revealed dysbiosis patients ms including reduction short chain fatty acid scfa administration scfa ameliorates disease severity eae association induction regulatory t cells moreover metabolites microbiota scfa tryptophan shown influence glial functions cns review introduce recent findings regarding interaction gut microbiota ms eae mspmid34433741 doi105692 clinicalneurolcn001590,1.0
myrtenal caryophyllene oxide screened liquidambaris fructus suppress nlrp3 inflammasome components rheumatoid arthritis background liquidambaris fructus lf infructescence liquidambar formosana traditional chinese medicine lf used treat joint pain common symptom arthritis rheumatism however lack pharmacological evidence limited applications modern clinics therefore study aims explore protective effect lf rheumatoid arthritis ra identify active ingredientsmethodsrats adjuvantinduced arthritis aia divided 4 groups administered petroleum ether extract lf pel ethyl acetate extract lf eel water extract lf wel piroxicam pir respectively 3 weeks two additional groups used normal control nc model control mc administered distilled water placebo clinical scores arthritis bone surface synovial inflammation cartilage erosion used evaluate therapeutic efficacy treatment serum il1 tnf level expression nlrp3 il1 caspase1 p20 synovial tissue aia rats evaluated elisa western blot active ingredients lf investigated using network pharmacology molecular docking methods inhibition nlrp3 inflammasome activation verified human rheumatoid arthritis fibroblastlike synovial cells rafls modelresultspel alleviate paw swelling bone joint destruction synovial inflammation cartilage erosion aia rats significantly superior efficacy eel wel pel reduced il1 tnf serum levels attenuated upregulation nlrp3 il1 caspase1 p20 expression synovial tissue aia rats network pharmacology molecular docking results indicated myrtenal caryophyllene oxide main two active ingredients pel two compounds showed significant inhibition tnf nlrp3 il1 caspase1 p20 expression raflsconclusionsmyrtenal caryophyllene oxide screened pel suppress activation nlrp3 inflammasome thereby alleviating ra symptoms,0.0
identification validation hub genes synovial tissue patients osteoarthritis rheumatoid arthritis background osteoarthritis oa rheumatoid arthritis ra two major joint diseases similar clinical phenotypes study aimed determine mechanistic similarities differences oa ra integrated analysis multiple gene expression data setsmethodsmicroarray data sets oa ra obtained gene expression omnibus geo integrating multiple gene data sets specific differentially expressed genes degs identified gene ontology go functional annotation kyoto encyclopedia genes genomes kegg pathways proteinprotein interaction ppi network analysis degs conducted determine hub genes pathways cell type identification estimating relative subsets rna transcripts cibersort algorithm employed evaluate immune infiltration cells iics profiles oa ra moreover mouse models ra oa established selected hub genes verified synovial tissues quantitative polymerase chain reaction qpcr resultsa total 1116 degs identified oa ra go functional enrichment analysis showed degs enriched regulation cell morphogenesis involved differentiation positive regulation neuron differentiation nuclear speck rna polymerase ii transcription factor complex protein serine threonine kinase activity proximal promoter sequencespecific dna binding kegg pathway analysis showed degs enriched egfr tyrosine kinase inhibitor resistance ubiquitin mediated proteolysis foxo signaling pathway tgfbeta signaling pathway immune cell infiltration analysis identified 9 iics significantly different distributions oa ra samples qpcr results showed expression levels hub genes rps6 rps14 rps25 rpl11 rpl27 snrpe eef2 rpl19 significantly increased oa samples compared counterparts ra samples p 005 conclusionthis largescale gene analyses provided new insights diseaseassociated genes molecular mechanisms well iics profiles oa ra may offer new direction distinguishing diagnosis treatment oa ra,0.0
expression clinical significance il7r nfatc2 rnf213 familial sporadic multiple sclerosis sci rep 2021 sep 28 11 1 19260 doi 101038 s41598021986915abstractmultiple sclerosis ms chronic inflammatory autoimmune disorder central nervous system characterized myelin loss axonal dysfunction increased production inflammatory factors cytokines implicated axon destruction present study compared expression level il7r nfatc2 rnf213 genes peripheral blood 72 ms patients 37 familial ms 35 sporadic ms 74 healthy controls 34 individuals family history disease 40 healthy controls without family history via realtime pcr results showed expression level il7r decreased sporadic patients comparison groups additionally increased nfatc2 expression level ms patients versus healthy controls increased expression nfatc2 sporadic familial groups compared controls familial group versus fdr also seen results also represented increased expression level rnf213 familial patients compared control group similar rnf213 expression sporadic control group well fdr familial group also seen diagnostic evaluation performed receiver operating characteristic roc curve analysis area curve auc calculation correlation clinical parameters including onset age expanded disability status scale edss gene expression levels also assessed overall decreased expression level il7r sporadic cases increased expression level nfatc2 may associated pathogenesis ms disease confirmation effects differential expression rnf213 gene requires studies wider statistical populationspmid34584155 doi101038 s41598021986915,1.0
interface multiple sclerosis depression vascular disease mortality populationbased matched cohort study neurology 2021 sep 1101212 wnl0000000000012610 doi 101212 wnl0000000000012610 online ahead printabstractobjectiveto assess whether association depression vascular disease mortality differs people ms compared age sex general practicematched controlsmethodswe conducted populationbased retrospective matched cohort study 1jan1987 30sep2018 included people ms matched controls without ms england stratified depression status used timevarying cox proportional hazard regression models test association ms depression time incident vascular disease mortality analyses also stratified sexresults12 251 people ms 72 572 matched controls identified baseline 21 people ms 9 controls depression compared matched controls without depression people ms increased risk incident vascular disease regardless whether comorbid depression 10year hazard allcause mortality 175fold greater controls depression 95ci 159191 388fold greater people ms without depression 95ci 366410 543fold greater people ms depression 95ci 488596 overall interaction ms status depression synergistic 14 observed effect attributable interaction sexstratified analyses confirmed differences hazard ratiosconclusionsdepression associated increased risks incident vascular disease mortality people ms effects depression ms allcause mortality synergistic studies evaluate whether effectively treating depression associated reduced risk vascular disease mortalitypmid34470802 doi101212 wnl0000000000012610,0.0
cellular immune response epsteinbarr virus decreases ocrelizumab treatment abstractbackgroundepsteinbarr virus ebv strongly associated multiple sclerosis ms initial infection ebv maintains lifelong latent infection b lymphocytes depletion b lymphocytes blood anticd20 antibody ocrelizumab markedly reduces disease activity ms objective measure effect ocrelizumab treatment cellular immune response ebvmethodsblood collected ms patients ocrelizumab treatment peripheral blood mononuclear cells stimulated various antigens response measured using tritiated thymidine proliferation elispot number interferon producing cellsresultsthe proliferation autologous ebvinfected cells lcl decreased 6 12 months treatment number interferon producing cells elispot response stimulation either lcl ebv also decreased responses varicella zoster virus influenza virus mitogen change significantlyconclusionthe cellular immune response ebv lcl decreases treatment ocrelizumab benefit ocrelizumab ms may removal ebv antigenic stimulus,0.0
clinical impact ocrelizumab extended interval dosing covid19 pandemic associations cd19+ bcell repopulation retrospective clinical audit 136 patients ms received ocrelizumab covid19 pandemic significant difference clinical relapse rate radiological activity 67 patients received extended interval dosing eid 30 weeks mean 48359 weeks compared standard interval dosing 30 weeks average followup 4 months cd19+ bcell repopulation occurred 94 p0001 eid patients reinfusion correlated strongly redosing interval rs0738 p00001 associated inflammatory disease activity eid impact shortterm disease activity despite significant cd19+ bcell repopulation warrants longterm prospective study,0.0
followup infectious mononucleosis search serological similarities presymptomatic multiple sclerosis abstractbackground two threefold increase risk multiple sclerosis ms infectious mononucleosis im observed cohort case control studies however association investigated prospectively im remains determined whether longterm immunospecific sequelae features consistent presymptomatic ms occur immethods sera obtained individuals acute im 20032007 n42 individuals followup fu study approximately 10 years im assayed antibodies variety epsteinbarr virus ebv antigens including gp350 novel recombinant glycoprotein ebv envelope similarly singleprotein antigens used assess measles varicellazoster reactivity ncore varicellazoster glycoprotein e vzvge fu study also included cerebrospinal fluid csf samples 21 individuals test igg antibodies viral antigens controls csf serum samples obtained 15 ebvseropositive volunteers denied history im serum samples obtained 24 ebvseropositive blood donors antigp350 antincore antivzvge igg levels also analysed sera csf samples 22 persons msresults fu assays showed higher antigp350 igg p0007 univariate among healthy controls difference serum antivca antiebna1 igg levels difference antigp350 csf samples antincore igg antivzvge higher acute im samples p 0001 p 00001 respectively fu although antincore remained heightened ageadjusted analysis fu p0014 compared control group ms group serum antigp350 antincore igg levels significantly higher among control group antivzvge levels csf antigp350 vzvge levels slightly higher among persons ms among control group whereas antincore igg markedly higher persons ms control groupconclusion present study im showed certain similarities ms increased antigp350 reactivity persisted decade im reminiscent established increased antiebv reactivity presymptomatic ms acute im associated increased antimeasles antivzv immunoreactivity similar mrz reaction ms evidence suggesting measles reactivity persisted decade,0.0
current international trends treatment multiple sclerosis children impact covid19 pandemic abstractbackground recently first diseasemodifying therapy approved children multiple sclerosis ms practice patterns including substantial offlabel use evolved understanding attitudes towards treatment paediatric ms whether changed due ongoing covid19 pandemic vital guide future therapeutic trials developing guidelines reflect practicemethods performed online survey within international paediatric multiple sclerosis study group july september 2020 survey sent 130 members 25 countries consisted five sections demographic data treatment disease modifying therapies covid19 outcome three patient casesresults survey completed 66 members 51 paediatric neurologists adult neurologists fingolimod interferons frequently used diseasemodifying therapies especially among paediatric neurologists almost third 31 respondents altered prescribing practice due covid19 particular beginning pandemicconclusions survey results indicate tendency moving traditional escalation therapy starting injectables towards early start newer highly effective disease modifying therapies covid19 pandemic slightly affected prescribing patterns treatment choices paediatric ms,0.0
circadian rhythms affect bone reconstruction regulating bone energy metabolism abstractmetabolism one complex cellular biochemical reactions providing energy substances basic activities cell growth proliferation early studies shown glucose important nutrient osteoblasts addition amino acid metabolism fat metabolism also play important roles bone reconstruction mammalian circadian clocks regulate circadian cycles various physiological functions vertebrates circadian rhythms mediated set central clock genes muscle brain arnt like1 bmal1 muscle brain arnt like2 bmal2 circadian rhythmic motion output cycle stagnates clock cryptochrome 1 cry1 cryptochrome2 cry2 period 1 per1 period 2 per2 period 3 per3 neuronal pas domain protein 2 npas2 negative feedback loops controlled transcriptional posttranslational levels adjust clock genes diurnal manner according results studies circadian transcriptomic studies several tissues rhythmic genes expressed tissuespecific manner affected tissuespecific circadian rhythms circadian rhythm regulates several activities including energy metabolism feeding time sleeping endocrine immune functions reported circadian rhythms mammals closely related bone metabolism review discuss regulation circadian rhythm circadian clock gene osteoblasts osteoclasts energy metabolism bone relationship circadian rhythm bone remodeling energy metabolism also discuss therapeutic potential regulating circadian rhythms changing energy metabolism bone development bone regeneration,0.0
studying microglia response oxidized phosphatidylcholine primary mouse neuron culture mouse spinal cord star protoc 2021 sep 27 2 4 100853 doi 101016 jxpro2021100853 ecollection 2021 dec 17abstractoxidized phosphatidylcholine oxpc found multiple sclerosis brain lesions mediates neurodegeneration microglia prominent responders oxpc insult thus studying protective noxious functions important help halt neurodegeneration present protocols including cell isolation culture animal surgeries well tissue processing isolation study microglia response oxpcmediated neurodegeneration vitro vivo complete details use execution protocol please refer dong et al 2021 pmid34622221 pmcpmc8482042 doi101016 jxpro2021100853,0.0
outcomes covid19 among patients treated subcutaneous interferon beta1a multiple sclerosis abstractbackground accordance expert guidance patients typically continued receive treatment subcutaneous interferon beta1a sc ifn 1a relapsing multiple sclerosis ms covid19 pandemicmethods provide summary outcomes among sc ifn 1atreated patients adverse events related confirmed suspected covid19 reported merck global patient safety database 2 february 2021 serious covid19related adverse events classified reporting clinician included leading hospitalization admission intensive care death outcomes classified per usual pharmacovigilance practiceresults evaluable cohort comprised 603 patients median age 43 range 1384 years 751 female covid19 experienced median 330 range 03218 months start treatment sc ifn 1a total 136 226 patients experienced serious covid19 events including 59 hospitalizations 4 patients admitted intensive care 5 deaths fatality rate 08 regarding nonfatal outcomes 478 patients 289 603 covid19 adverse events recovered recovering time analysis similar findings apparent serious hospitalized cohortsconclusion findings analysis merck global patient safety database suggest compared available statistics general population ms patients receiving sc ifn 1a treatment relapsing ms relatively low rates serious disease severe outcomes covid19,0.0
effects mesenchymal stem cellderived exosomes autoimmune diseases front immunol 2021 sep 27 12749192 doi 103389 fimmu2021749192 ecollection 2021abstractrecent years immunosuppressive properties mesenchymal stem cells mscs demonstrated preclinical studies trials inflammatory autoimmune diseases emerging evidence indicates immunomodulatory effect mscs primarily attributed paracrine pathway one key paracrine effectors mesenchymal stem cellderived exosomes mscexos small vesicles 30200 nm diameter play important role celltocell communication carrying bioactive substances parental cells recent studies support finding mscexos obvious inhibitory effect toward different effector cells involved innate adaptive immune response moreover substantial progress made treatment autoimmune diseases including multiple sclerosis ms systemic lupus erythematosus sle type1 diabetes t1dm uveitis rheumatoid arthritis ra inflammatory bowel disease ibd mscexos capable reproducing msc function overcoming limitations traditional cell therapy therefore using mscexos instead mscs treat autoimmune diseases appears promising cellfree treatment strategy review review current understanding mscexos discuss regulatory role mscexos immune cells potential application autoimmune diseasespmid34646275 pmcpmc8503317 doi103389 fimmu2021749192,1.0
impact covid19 public health measures myelin oligodendrocyte glycoprotein iggassociated disorders children abstractbackgrounddespite better characterization spectrum mogiggassociated disorders mogad children role infection pathophysiology remains unclear goal study evaluate public health measures put place prevent spread sarscov2 march 2020 ontario canada associated change incidence mogad neuroinflammatory disorders childrenmethodologywe reviewed singlecentre cohort children referred suspicion neuroinflammatory disorder january 2015 march 2021 age date sex diagnosis mogigg antibodies status detected pathogens presentation identified comparative statistical analysis performed based diagnosis years seasons using pearsonnulls chisquared test fishernulls exact test categorical variables using anova kruskalwallis test continuous variables appropriate compared postlockdown period march 17th 2020 march 31st 2021 previous calendar years 2015 2019 alone previous calendar years prelockdown 2020 period january 1st 2020 march 16th 2020 pvalue 005 considered significant posthoc pairwise comparisons postlockdown period previous years performed significant results false discovery rate adjustment adjusted pvalue qvalue 005 computed hypothesized number new mogad significantly lower postlockdown period compared previous years due decreased regional pathogen transmissionresultsamong 491 referred cases identified 415 new cases neuroinflammatory disorder january 2015 march 2021 number new neuroinflammatory disorder diagnoses change years noted significantly fewer new mogad diagnoses 2020 compared previous years mogad patients presenting 2020 spring lockdown q00009 addition significantly fewer parainfectious neuroinflammatory cases q004 pathogen detected q004 postlockdown period number new multiple sclerosis ms aquaporin4 neuromyelitis optica spectrum disorders aqp4nmosd cases remained stable despite lockdown q0185 0693 respectively interpretationenhanced populationbased infection control strategies may role modulating incidence mogad parainfectious neuroinflammatory disorders ms aqp4nmosd,1.0
infection incidence management multiple sclerosis patients initiating diseasemodifying therapy abstractdiseasemodifying therapies multiple sclerosis ms effective frequently cost 70 000+ year can predispose patients serious infections retrospective cohort analysis n3 204 compared rates infections 24month period ms medication route administration antimicrobial use infection rates 387 oral 373 infused 368 injectable infections antimicrobials prescribed 865 oral 843 infused 855 injectable cases found differences within bacterial herpes zoster infection rates antimicrobial use among new users medication route administration findings suggest pharmacovigilance may inform shareddecision processes choosing ms medications,0.0
evidence loss natalizumab effectiveness every6week dosing propensity scorematched comparison every4week dosing patients enrolled tysabri observational program top ther adv neurol disord 2021 sep 27 1417562864211042458 doi 101177 17562864211042458 ecollection 2021abstractbackground extended interval dosing natalizumab associated significantly lower progressive multifocal leukoencephalopathy risk compared every4week q4w dosing patients relapsingremitting multiple sclerosis previous studies suggested natalizumab effectiveness maintained patients switch q4w extended interval dosing limited lack wellmatched patient cohortsmethods tysabri observational program top data november 2019 used identify patients relapsingremitting multiple sclerosis treated natalizumab q4w single physicianindicated dosing change q4w every6week q6w dosing 1 year q4w treatment patients propensity score matched time switch q4w q6w dosing clinical outcomes annualized relapse rate probability remaining relapse free free 24week confirmed disability worsening safety outcomes assessed two cohortsresults study included 219 pairs propensity scorematched q6w q4w patients annualized relapse rates similar q6w 0150 q4w 0157 patients probability remaining relapse free hazard ratio 1243 95 confidence interval 08191888 p 0307 remaining free 24week confirmed disability worsening hazard ratio 0786 95 confidence interval 02842176 p 0644 differ significantly q6w q4w patients summarized safety results matched q6w q4w patients also presentedconclusion realworld findings wellmatched patient cohorts top demonstrate natalizumab effectiveness maintained patients switch q6w dosing 1 year q4w dosingclinicaltrialsgov identifier nct00493298pmid34603507 pmcpmc8481711 doi101177 17562864211042458,0.0
applying deep learning accelerated clinical brain magnetic resonance imaging multiple sclerosis front neurol 2021 sep 27 12685276 doi 103389 fneur2021685276 ecollection 2021abstractbackground magnetic resonance mr scans routine clinical procedures monitoring people multiple sclerosis pwms patient discomfort timely scheduling financial burden motivate need accelerate mr scan time examined clinical application deep learning dl model restoring image quality accelerated routine clinical brain mr scans pwms methods acquired fast 3d t1w bravo fast 3d t2w flair mri sequences half phase encodes half number slices parallel conventional parameters using subset scans trained dl model generate images fast scans quality similar conventional scans applied model remaining scans calculated clinically relevant t1w volumetrics normalized whole brain thalamic gray matter white matter volume scans t2 lesion volume subanalysis performed paired ttests comparing conventional fast fast dl volumetrics fit repeated measures mixedeffects models test differences correlations volumetrics clinically relevant patientreported outcomes pro results found statistically significant small differences conventional fast scans dl t1w volumetrics difference extent key t1w volumetrics correlated clinically relevant pros ms symptom burden neurological disability conclusion deep learning model improves image quality accelerated routine clinical brain mr scans potential inform clinically relevant outcomes mspmid34646227 pmcpmc8504490 doi103389 fneur2021685276,0.0
integrated management multiple sclerosis spasticity associated symptoms using spasticityplus syndrome concept results structured specialists#39 discussion using workmat methodology front neurol 2021 sep 27 12722801 doi 103389 fneur2021722801 ecollection 2021abstractbackground multiple sclerosis ms treatment radically improved last years however ms symptom management still challenging novel spasticityplus syndrome conceptualized frame several spasticityrelated symptoms can addressed together broadspectrum medication certain cannabinoidbased drugs aim project gain insight spanish neurologists clinical experience ms spasticity associated symptoms assess acknowledgment applicability spasticityplus syndrome concept patients ms methods ten online meetings conducted using workmat methodology allow structured discussions fiftyfive spanish neurologists experts ms management completed discussed set predefined exercises comprising ms symptom assessment management clinical practice ms symptoms clustering clinical practice perception spasticityplus syndrome concept document presents quantitative qualitative results discussions results specialists considered polytherapy common concern ms simplifying management ms spasticity associated manifestations useful generally agreed ms spasticity diagnosed moderate severe forms appear according neurologists clinical experience symptoms commonly associated ms spasticity included spasms cramps 100 specialists pain 85 bladder dysfunction 62 bowel dysfunction 42 sleep disorders 42 sexual dysfunction 40 multiple correspondence analysis revealed two main symptom clusters spasticityspasms crampspain ataxiainstabilityvertigo twelve 16 symptoms 75 scored 7 010 qol impact scale specialists representing moderatehigh impact ms specialists considered pain spasticity spasms cramps bladder dysfunction depression treatment priority given frequency chance therapeutic success neurologists agreed usefulness new spasticityplus syndrome concept manage spasticity associated symptoms together experience treatments targeting cannabinoid system satisfactory conclusions applicability new concept spasticityplus ms clinical practice seems possible may lead integrated management several ms symptoms thus reducing treatment burden disease symptomspmid34646229 pmcpmc8503561 doi103389 fneur2021722801,0.0
cannabis related side effects otolaryngology scoping review background cannabis rapidly legalized north america however limited evidence exists around side effects health canada defines side effect harmful unintended response health product given drug safety concerns studys purpose review unintended side effects cannabis otolaryngologymethodsthe preferred reporting items systematic reviews metaanalysis extension scoping reviews prismascr protocol used conduct scoping review medline embase cinahl central databases prospero crd42020153022 english studies adults included inception end 2019 invitro animal studies n 5 excluded primary outcome defined unintended side effects defined otolaryngology symptom diagnosis following cannabis use oxford centre evidencebased medicine levels evidence risk bias using risk bias randomized trials rob 2 risk bias nonrandomized studies interventions robinsi tools assessed two authors independently reviewed studies senior author settled discrepanciesresultsfive hundred twentyone studies screened 48 studies analysed subspecialties comprised head neck 32 otology 8 rhinology 5 airway 5 laryngology 1 cannabis use associated unintended tinnitus vertigo hearing loss infection malignancy sinusitis allergic rhinitis thyroid dysfunction dyspnea half 541 studies showed increased side effects change symptoms following cannabis use oxford levels evidence 24 substantial heterogeneity risk bias assessment rob2 low high robins1 moderate criticalconclusionthis first comprehensive scoping review unintended side effects cannabis otolaryngology current literature limited lacks highquality research future randomized studies needed focus therapeutic effects cannabis otolaryngology substantial work remains guide clinicians suggest safe evidencebased choices cannabis usegraphic abstract,0.0
serum gfap nfl levels benign relapsingremitting multiple sclerosis abstractobjectivewe aimed investigate serum glial fibrillary acidic protein gfap serum neurofilament light chain nfl levels potential discriminative biomarkers benign relapsingremitting multiple sclerosis brrms aggressive relapsingremitting ms arrms methodsserum gfap nfl levels analyzed patients brrms n34 arrms n29 healthy controls n14 using single molecule array simoa patients arrms treated highly effective diseasemodifying treatments dmt fingolimod natalizumab resultsserum gfap levels brrms median 21019 pg ml iqr 16369 28719 arrms median 18860 pg ml iqr3923 24493 significantly higher p0035 p0034 respectively compared healthy controls median 11793 pg ml iqr 6028 18383 serum gfap levels differ brrms arrms statistical differences nfl levels brrms arrms healthy controls gfap level significantly higher p004 brrms without dmt median 21604 pg ml iqr 18860 27479 brrms patients used dmt median 19626 pg ml iqr 13333 32554 conclusionswe found elevated levels serum gfap brrms arrms compared healthy controls reflecting astrocytic activation serum nfl differ brrms arrms probably due stable inflammatory phase disease effective dmt use arrms single serum nfl gfap measurements separate patient brrms effectively treated arrms long history disease thus consecutive samples needed followup,0.0
multiple sclerosis sarscov2 interplay started front immunol 2021 sep 27 12755333 doi 103389 fimmu2021755333 ecollection 2021abstractcurrent knowledge multiple sclerosis ms etiopathogenesis encompasses complex interactions hosts genetic background several environmental factors result dysimmunity central nervous system oldaged association exists ms viral infections capable triggering sustaining neuroinflammation direct indirect mechanisms novel coronavirus sarscov2 remarkable still fully understood impact immune system occurrence severity acute covid19 postinfectious chronic illness long covid19 largely depends hosts response infection echoes several aspects ms pathobiology furthermore msassociated viruses epsteinbarr virus ebv human endogenous retroviruses hervs may enhance mechanistic interplay novel coronavirus potential interfere ms natural history studies covid19 people ms helped clinicians adjusting therapeutic strategies pandemic similar efforts made sarscov2 vaccination campaigns review look 18 months sarscov2 pandemic perspective ms dissect neuroinflammatory demyelinating mechanisms associated covid19 summarize pathophysiological crossroads ms sarscov2 infection discuss present evidence covid19 vaccination people mspmid34646278 pmcpmc8503550 doi103389 fimmu2021755333,1.0
targeting rnabinding protein hur potential therapeutic approach neurological disorders focus amyotrophic lateral sclerosis als spinal muscle atrophy sma multiple sclerosis int j mol sci 2021 sep 27 22 19 10394 doi 103390 ijms221910394abstractthe importance precise co posttranscriptional processing rna regulation gene expression become increasingly clear rnabinding proteins rbps class proteins bind single doublechain rna different affinities selectivity thus regulating various functions rna fate cells elav embryonic lethal abnormal visual system hu proteins represent important family rbps play key role fate newly transcribed mrna elav proteins bind aurich element containing transcripts usually present mrna proteins cytokines growth factors proteins involved neuronal differentiation maintenance review focused member elav hu proteins hur role development neurodegenerative disorders particular focus demyelinating diseasespmid34638733 doi103390 ijms221910394,1.0
improving smoking cessation support people multiple sclerosis qualitative analysis clinicians views current practice abstractintroduction smoking key modifiable risk factor multiple sclerosis ms ms healthcare providers central role informing people deleterious effects smoking ms progression promote smoking cessation yet limited information smoking cessation support provided providers study aimed gain understanding ms healthcare providers current practices barriers facilitators related providing smoking cessation support people msmethods total 13ms nurses 6 neurologists working public private ms clinics across australia recruited professional networks ms organisations telephone interviews conducted transcribed evaluated using framework analysisresults ms nurses neurologists reported routinely assess smoking status people ms initial appointments less regularly also followup appointments clinicians considered important provide information smoking impact ms health outcomes advise cease smoking content delivery varies beyond clinicians offer referral smoking cessation support others stated responsibility especially light competing priorities many unsure referral pathways options requiring information training resourcesconclusion results research indicate potential improve support ms clinicians promote smoking cessation among people ms smoking cessation support may include tailored patient resources clinician training stronger collaboration smoking cessation service providers,0.0
acute demyelinating syndromes report child neurology department sfax university hospital abstractintroductionthe yearly incidence acute demyelinating syndromes ads multiethnic cohort children published langergould al 2011 estimated 166 per 100 000 nevertheless real incidence disorders still underestimated iterative revision diagnosis criteria failed classify significant number children adspurposethis work aimed describe clinical paraclinical characteristics ads pediatric populationmaterial methodsdemographic clinical paraclinical data 42 children 24 females 18 male sr133 collected medical records patients admitted child neurology department sfax university hospital 2008 2021 clinical events presumed inflammatory origin next patients categorized per m n nouri al dated classification ads finally characteristics different ads categories comparedresultsthe mean age onset 6 years 35 years mean followup period 28 months 69 patients monophasic course ads pediatric population acute disseminated encephalomyelitis adem 36 clinically isolated syndrome cis 24 multiple sclerosis ms 19 neuromyelitis optica spectrum disorder nmosd 7 myelin oligodendrocyte glycoprotein antibodiesassociated diseases mogad 2 recurrent demyelinating disease otherwise specified rdnos 10 presentation patients showed different clinical picture according adssubtype patients epileptic seizure ademgroup 533 optic neuritis cisgroup 70 motor deficit msgroup 625 area postrema syndrome nmosdgroup 333 vesicosphincter dysfunction rdnosgroup 75 among patients presenting visual impairment 214 visual evoked potential vep guided diagnosis nmosd 222 objectifying axonal optic nerve damage different ads subtypes identified according mri results 100 adempatients 75 mspatients antibody testing three patients adssubtype recognized based antibody testing three patients two patients cisgroup first isolated optic neuritis positive antiaquaporin 4 antibodies antiaqp4 clinically polyfocal ads positive antinuclear antibodies ana type antirnp remaining patients presented ademphenotype positive antimyelin oligodendrocyte glycoprotein antimog significancerecognizing distinctive features ads category may improve diagnosis accuracy well indication suitable treatment,1.0
improving detection treatment depression australians multiple sclerosis qualitative analysis abstractbackgrounddepression common people multiple sclerosis ms yet often goes undetected untreated undertreatedobjectivethis qualitative research explored current practices barriers facilitators detection treatment depression australians msmethodsparticipants 26 people ms recruited social media participants completed centre epidemiological studies depressionrevised cesdr scale indepth telephone video interviews interviews analysed using framework analysisresultsscores measured cesdr proposed 73 participants experiencing severe depression symptoms participants reported depression regularly formally assessed ms healthcare services offered limited information depression ms barriers mental health support included recognition depression resistance treatment limitations collaborative support general practitioners ms healthcare services participants expressed need open conversations information depression neurology consultationsconclusionbased findings improved detection treatment depression people ms requires 1 better provision information depression people ms healthcare services community organisations 2 regular screening assessment 3 better healthcare services collaboration improve management,0.0
correction whole brain 3d mr fingerprinting multiple sclerosis pilot study correction bmc med imaging 2021 2188 https doiorg 101186 s12880021006205following publication original article 1 authors requested include following acknowledgements section initially omittedthe authors like acknowledge support ge healthcare university pisa proving mr fingerprinting sequence analysis softwarethe original article already corrected,0.0
clinician#39 s attitude enteral nutrition percutaneous endoscopic gastrostomy survey china background percutaneous endoscopic gastrostomy peg recommended longterm enteral nutrition however longterm nasogastric ngt feeding still commonplace china surveyed chinese clinicians opinions toward peg feeding order identify potential barriers acceptancy peg feedingmethodsa selfreported questionnaire developed distributed 600 doctors fivepoint likert scales used responsesresultsof 525 respondents mainly nutritional support method ngt peg less used doctors working tertiary class hospitals radiotherapy department likely choose peg feeding p 0000 overall 241 46 participants know peg 284 54 different understanding degree peg age p 0002 working life p 0044 professionalism p 0005 significantly related understanding peg levels agreement high score 347 using peg patients prolonged strokeassociated dysphagia high agreement level statement peg unnecessary ngt sustain basic needs patients though better outcome can predicted peg feeding highest scoring factor score 391 influenced clinicians choice peg resistance patients families second one poor cooperation among departments score 380 conclusionsdoctors insufficient knowledge peg feeding resistance patients families poor cooperation among departments factors leading physicians prefer conservative treatment avoid disputes rather better ones,0.0
electroacupuncture improves repeated social defeat stresselicited social avoidance anxietylike behaviors reducing lipocalin2 hippocampus background posttraumatic stress disorder ptsd traumarelated disorder associated proinflammatory activation neurobiological impairments brain leads series affectivelike behaviors electroacupuncture ea proposed clinically useful therapy several brain diseases however potential role ea treatment ptsd molecular cellular mechanisms rarely investigatedmethodswe used established preclinical social defeat stress mouse model study whether ea treatment modulates ptsdlike symptoms understand underlying mechanisms end male c57bl 6 mice subjected repeated social defeat stress rsds 6 consecutive days induce symptoms ptsd treated ea baihui gv 20 dazhui gv 14 acupointsresultsthe stimulation ea needle insertion baihui gv 20 dazhui gv 14 acupoints effectively improved ptsdlike behaviors social avoidance anxietylike behaviors however ea stimulation bilateral tianzong si11 acupoints affect ptsdlike behaviors obtained rsds ea stimulation also markedly inhibited astrocyte activation dorsal ventral hippocampi rsdstreated mice using nextgeneration sequencing analysis results showed ea stimulation attenuated rsdsenhanced lipocalin 2 expression hippocampus importantly using doublestaining immunofluorescence observed increased lipocalin 2 expression astrocytes rsds also reduced ea stimulation addition intracerebroventricular injection mouse recombinant lipocalin 2 protein lateral ventricles provoked social avoidance anxietylike behaviors activation astrocytes hippocampus interestingly overexpression lipocalin 2 brain also altered expression stressrelated genes including monoamine oxidase monoamine oxidase b mineralocorticoid receptor glucocorticoid receptor hippocampusconclusionsthis study suggests treatment ea baihui gv 20 dazhui gv 14 acupoints improves rsdsinduced social avoidance anxietylike behaviors astrocyte activation lipocalin 2 expression furthermore findings also indicate lipocalin 2 expression brain may important biomarker development ptsdrelated symptoms,0.0
absence apolipoprotein e associated exacerbation prion pathology promotes microglial neurodegenerative phenotype abstractprion diseases prionoses group rapidly progressing invariably fatal neurodegenerative diseases pathogenesis prionoses associated selfreplication connectomal spread prpsc disease specific conformer prion protein microglia undergo activation early course prion pathogenesis exert opposing roles prpsc mediated neurodegeneration clearance prpsc apoptotic neurons diseaselimiting effect microgliadriven neuroinflammation bears deleterious consequences neuronal networks apolipoprotein apo e lipid transporting protein pleiotropic functions include controlling phagocytic inflammatory characteristics activated microglia neurodegenerative diseases despite significance microglia prion pathogenesis role apoe prionoses established showed infection wild type mice 22l mouse adapted scrapie strain associated significant increase total brain apoe protein mrna levels also conspicuous celltype shift apoe expression reduced expression apoe activated astrocytes marked upregulation apoe expression activated microglia also showed apoe ablation exaggerates prpsc mediated neurodegeneration apoe mice shorter disease incubation period increased load spongiform lesion pronounced neuronal loss exaggerated astro microgliosis astrocytes apoe mice display salient upregulation transcriptomic markers defining a1 neurotoxic astrocytes microglia show upregulation transcriptomic markers characteristic microglial neurodegenerative phenotype impaired clearance prpsc dying neurons microglia apoe mice along increased level proinflammatory cytokines work indicates apoe absence renders clearance prpsc dying neurons microglia inefficient excess neuronal debris promotes microglial neurodegenerative phenotype aggravating vicious cycle neuronal death neuroinflammation,0.0
addressing hypoxia paradox severe covid19 literature review report four cases treated erythropoietin analogues background since fall 2019 sarscov2 spread worldwide causing major pandemic estimated 220 million subjects affected september 2021 severe covid19 associated multiple organ failure particularly lung kidney also grave neuropsychiatric manifestations overall mortality reaches 2 vaccine development thrived thus far unreached dimensions will one prerequisite terminate pandemic despite intensive research however treatment options modifying covid19 course outcome emerged since pandemic outbreak additionally substantial threat serious downstream sequelae called long covid neurocovid becomes increasingly evidentmain body abstractamong candidates suggested yet receive appropriate funding clinical trials recombinant human erythropoietin based accumulating experimental clinical evidence erythropoietin expected 1 improve respiration organ function 2 counteract overshooting inflammation 3 act sustainably neuroprotective neuroregenerative recent counterintuitive findings decreased serum erythropoietin levels severe covid19 support relative deficiency erythropoietin condition can therapeutically addressed also made us coin term hypoxia paradox review paradox likely due uncoupling physiological hypoxia signaling circuits mediated detrimental gene products sarscov2 unfavorable host responses including micrornas dysfunctional mitochondria substitution erythropoietin might overcome hypoxia paradox caused deranged signaling improve survival functional status covid19 patients longterm outcome supporting hints embedded review present 4 male patients severe covid19 unfavorable prognosis including predicted high lethality profoundly improved upon treatment included erythropoietin analoguesshort conclusionsubstitution epo mayamong beneficial epo effects severe covid19circumvent downstream consequences hypoxia paradox doubleblind placebocontrolled randomized clinical trial proofofconcept warranted,1.0
associations multiple sclerosis incidence heart diseases systematic review metaanalysis observational studies abstractbackground observational studies described associations multiple sclerosis ms heart diseases results mixedmethods medline embase cochrane central searched 5 october 2020 according protocol prospero registration number crd42020184493 included longitudinal nonrandomized studies exposure comparing incidence acquired heart diseases people multiple sclerosis pwms people without multiple sclerosis used robinse grade approach assess risk bias certainty evidence respectively data pooled using randomeffect modelsresults 5 156 studies nine studies met inclusion criteria ms associated increased risk myocardial infarction hr 16 95 ci 12 20 i2 86 n1 209 079 heart failure hr 17 95 ci 13 22 i2 49 n489 814 associations pronounced among women younger people subgroup analyses found difference ischemic heart disease hr 10 95 ci 08 14 i2 86 n679 378 bradycardia hr 15 95 ci 04 50 i2 50 n187 810 risk atrial fibrillation lower pwms 07 95 ci 06 08 i2 0 n354 070 risk bias high certainty evidence rated low one study found cases infectious endocarditis among pwms hr 12 95 ci 10 14 n83 712 conclusions myocardial infarction heart failure considered people multiple sclerosis followup examinations,0.0
fundamentally different roles neuronal tnf receptors cns pathology tnfr1 ikk promote microglial responses tissue injury demyelination tnfr2 protects excitotoxicity mice j neuroinflammation 2021 sep 26 18 1 222 doi 101186 s12974021022004abstractbackground inflammatory demyelination tnf receptor 1 tnfr1 mediates detrimental proinflammatory effects soluble tnf soltnf whereas tnfr2 mediates beneficial effects transmembrane tnf tmtnf oligodendroglia microglia possibly cell types model supports use selective inhibitors soltnf tnfr1 antiinflammatory drugs central nervous system cns diseases potential obstacle neuroprotective effect soltnf pretreatment described cultured neurons relevance vivo unknownmethods address question generated mice neuronspecific depletion tnfr1 tnfr2 inhibitor nfb kinase subunit ikk main downstream mediator tnfr signaling applied experimental models inflammatory demyelination acute preconditioning glutamate excitotoxicity also investigated molecular cellular requirements soltnf neuroprotection generating astrocyteneuron cocultures different combinations wildtype wt tnf tnfr knockout cells measuring nmethyldaspartate nmda excitotoxicity vitroresults neither neuronal tnfr1 tnfr2 protected mice inflammatory demyelination fact neuronal tnfr1 neuronal ikk promoted microglial responses tissue injury tnfr1 required oligodendrocyte loss axonal damage cuprizoneinduced demyelination contrast neuronal tnfr2 increased preconditioning protection kainic acid ka excitotoxicity model mice limited hippocampal neuron death protective effects neuronal tnfr2 observed vivo investigated vitro previously described pretreatment astrocyteneuron cocultures soltnf therefore tnfr1 protected nmda excitotoxicity however protection dependent astrocyte neuronal tnfr1 astrocyte tmtnfneuronal tnfr2 interactions reproduced tnfr2 agonistconclusions results demonstrate neuronal tnf receptors perform fundamentally different roles cns pathology vivo neuronal tnfr1 ikk promoting microglial inflammation neurotoxicity demyelination neuronal tnfr2 mediating neuroprotection excitotoxicity also reveal previously described neuroprotective effects soltnf glutamate excitotoxicity vitro indirect mediated via astrocyte tmtnfneuron tnfr2 interactions results consolidate concept selective inhibition soltnf tnfr1 maintenance tnfr2 function combined antiinflammatory neuroprotective properties required safe treatment cns diseasespmid34565380 doi101186 s12974021022004,1.0
il33 genetics epigenetics immunerelated diseases abstractinterleukin33 il33 30kda protein belongs interleukin1 cytokine family crucial regulator innate adaptive immune responses interleukin additionally involved inflammatory reaction versus helminthic infections interleukin 33 acts group 2 innate lymphoid cells mast cells macrophages dendritic cells cd4 + th2 cells eliciting type 2 immune response moreover cytokine can activate st2 tregs demonstrating ability downregulate inflammation il33 also intracellular function regulating transcription active il33 doesnt signal peptide released across normal secretory pathway interleukin released cells damages acts like alarmin influence immune activation slightly adjusted via fine epigenetic interactions involving cascade pathways immune genes due diverse data emerged different experimental research decided span literature clarify much possible il33 influenced influence gene expression authors reported balance influenced according tissue considered fundamental immunerelated diseases il33 key role controlling inflammation understanding cytokine switch will fundamental near future order block activate immune pathways fact control interleukins effects monoclonal antibodies also using sirna mirnas silencing expressing key genes,0.0
factors associated fingolimod rebound single center reallife experience abstractbackground still controversial whether relapse experienced discontinuation fingolimod treatment rebound increasing cases rebound reported literature rate fingolimod rebound patients fingolimod cessation reported 5 52 present study aims determine rate rebound discontinuation fingolimod treatment factors affecting reboundmethods retrospective cohort study consists adult ms patients admitted hacettepe university hospital neurology ms center outpatient clinic 2012 2020results study period 642 patients received fingolimod 231 discontinued fingolimod treatment thirteen 126 patients rebound 103 fingolimod discontinuation patients rebound group significantly younger washout period significantly longer nonrebound group discontinuation fingolimod treatment edss score rebound group significantly higher nonrebound group annualized relapse rates similarconclusion younger age longer washout time previous treatment preferences may increase occurrence probability rebound recommended patients closely monitored fingolimod discontinuation appropriate diseasemodifying therapy initiated soon possible,0.0
characteristics secondary progressive multiple sclerosis disease activity provision care germany registrybased#x2f multicentric cohort study abstractbackground tailored immunomodulatory treatment strategy secondary progressive multiple sclerosis spms depends disease activityobjective assess realworld situation monitoring disease activity spms patients identify associations resulting subgroups demographics symptomatology therapymethods study included 4 263 spms patients german ms register gmsr classification activenull inactivenull according relapse activity mri findings year prior latest clinical visit used following definitions active gadolinium enhancing gd+ new t2 lesions 1 relapse inactive neither gd+ new t2 lesions relapses active inactive unclassifiable patients compared terms clinical data sociodemographics symptomatology healthcare dmtresults classification possible 1 513 355 spms patients 467 classified active 1 046 inactive classification mri data available 332 4 263 patients higher mri frequencies observed younger patients 122 112 133 per 10 years short disease duration 119 109 130 per 10 years p0001 conclusion mri coverage low especially elderly spms patients roughly one third spms patients presented markers disease activity last year overall clinical differences concerning symptomatology care patients active inactive spms small,0.0
lama2 loxl4 candidate fsgs genes background focal segmental glomerulosclerosis fsgs histologic pattern injury characterizes wide spectrum diseases many genetic causes identified fsgs even families comprehensive testing significant proportion remain unexplainedmethodsin family adultonset autosomal dominant fsgs linkage analysis performed 11 family members followed whole exome sequencing wes 3 affected relatives identify candidate genesresultspathogenic variants known nephropathy genes excluded subsequently linkage analysis performed narrowed disease gene s within 3 genome wes identified 5 heterozygous rare variants sequenced 11 relatives dna available two variants lama2 loxl4 remained candidates segregation analysis encode extracellular matrix proteins glomerulus renal biopsies showed classic segmental sclerosis hyalinosis lesion background mild mesangial hypercellularity examination basement membranes electron microscopy showed regions dense mesangial matrix one individual wider glomerular basement membrane gbm thickness two individuals compared historic control averagesconclusionsbased findings postulate additive effect digenic inheritance heterozygous variants lama2 loxl4 leads adultonset fsgs limitations study includes absence functional characterization support pathogenicity alternatively identification additional fsgs cases suspected deleterious variants lama2 loxl4 will provide evidence disease causality thus report will benefit renal community sequencing renal disease becomes widespread,0.0
potential biomarkers associated multiple sclerosis pathology int j mol sci 2021 sep 25 22 19 10323 doi 103390 ijms221910323abstractmultiple sclerosis ms complex disease central nervous system cns involves intricate aberrant interaction immune cells leading inflammation demyelination neurodegeneration due heterogeneity clinical subtypes diagnosis becomes challenging best treatment easily provided patients biomarkers used simplify diagnosis prognosis ms well evaluate results clinical treatments recent years research biomarkers advanced rapidly due ability easily promptly measured specificity reproducibility biomarkers classified several categories depending whether address personal predictive susceptibility diagnosis prognosis disease activity response treatment different clinical courses ms identified members indicate variety pathological processes ms neuroaxonal damage gliosis demyelination progression disability remyelination among others present review analyzes biomarkers cerebrospinal fluid csf blood serum promising imaging biomarkers used clinical practice furthermore aims shed light criteria challenges biomarker must face considered standard daily clinical practicepmid34638664 doi103390 ijms221910323,1.0
unusual case isolated acute aphasia multiple sclerosis cureus 2021 sep 25 13 9 e18278 doi 107759 cureus18278 ecollection 2021 sepabstractacute flare multiple sclerosis usually presents sensorimotor deficits limbs one side face optic neuritis internuclear ophthalmoplegia cerebellar signs symptoms isolated aphasia observed handful cases herein present case patient presented isolated transcortical motor aphasia initial thought patient cerebrovascular accident history uncontrolled hypertension later found magnetic resonance imaging mri brain patient demyelinating lesions compatible new symptoms exhibited excellent response intravenous methylprednisolone therapy discharged outpatient evaluation immunotherapypmid34722056 pmcpmc8545555 doi107759 cureus18278,1.0
atopic dermatitis risk autoimmune diseases systematic review metaanalysis background atopic dermatitis common chronic inflammatory skin disease presents major public health burden worldwide recent observational studies revealed potential association atopic dermatitis autoimmune disorders however metaanalysis prevalence incidence autoimmune diseases atopic dermatitis therefore considering potential clinical implications associations aimed assess risk autoimmune diseases patients atopic dermatitis using methodmethodspubmed embase web science searched inception october 2020 observational studies provided estimate effects 95 ci raw data included quality selected studies evaluated using newcastleottawa scale odds ratio relative risks pooled using random effects model expressed 95 confidence intervalsresultsfourteen observational studies included systematic review metaanalysis randomeffects metaanalysis casecontrol crosssectional studies showed significant association atopic dermatitis mutiple autoimmune diseases including alopecia areata celiac disease crohns disease rheumatoid arthritis systematic lupus erythematosus ulcerative colitis vitiligo furthermore pooling results cohort studies showed patients atopic dermatitis likely develop autoimmune diseasesconclusionour metaanalysis showed patients atopic dermatitis higher risk multiple autoimmune diseases including alopecia areata celiac disease crohns disease rheumatoid arthritis systematic lupus erythematosus ulcerative colitis vitiligo important early detection affected group timely management can initiated dermatologists allergists aware autoimmune diseases patients atopic dermatitis develop interventions necessary also limited present research still require largescale studies establish association atopic dermatitis autoimmune diseases,0.0
il1primed mesenchymal stromal cells exert enhanced therapeutic effects alleviate chronic prostatitis#x2f chronic pelvic pain syndrome systemic immunity background chronic prostatitis chronic pelvic pain syndrome cp cpps seriously affects patient health despite elusiveness innate therapeutic effects mesenchymal stromal cells mscs hold great promise inflammationrelated diseases recent evidence indicates diseasespecific inflammatory cytokines enhance therapeutic effects mscsmethodsby establishing cp cpps mouse model pretreating mscs cytokine interleukin1 il1 studied il1primed msc immunoregulatory ability targeted migration ability vitro cp cpps miceresultsil1 levels significantly increased prostate tissue serum experimental autoimmune prostatitis eap mice pretreatment il1 enhanced immunomodulatory potential targeted migration mscs vitro furthermore intravenous infusion il1primed mscs dampened inflammation prostate tissues alleviated hyperalgesia eap mice infused mscs inhibited monocyte infiltration promoted regulatory t lymphocyte formation prostate tissue thus remodeling local environment surprisingly il1primed mscs exhibited improved accumulation spleen prostate tissue accordingly infused mscs reshaped systemic immunity reducing proportion ly6chighcd11b+ monocytes boosting proportion cd4+foxp3+ regulatory t lymphocytes spleen lung inflammatory chemokine cc motif ligand 2 ccl2 decreased downregulation nfb jnk mapk pathways inflammatory resolution via mscs infusion alleviate painconclusionin summary il1primed mscs restored systemic immunologic homeostasis alleviate cp cpps modulating systemic immunity findings provide novel strategy boost therapeutic effects mscbased therapy cp cpps reveal essential role systematic immunity treatment cp cpps msc infusion,0.0
systemic inflammation alters neuroinflammatory response prospective clinical trial traumatic brain injury background neuroinflammation following traumatic brain injury tbi shown associated secondary injury development however systemic inflammatory mediators affect fully understood aim study see systemic inflammation affects markers neuroinflammation inflammatory response temporal correlation compartments different compartments differ cytokine compositionmethodstbi patients recruited previous randomised controlled trial studying effects drug anakinra kineret human recombinant interleukin1 receptor antagonist rhil1ra used n 10 treatment arm n 10 control arm cytokine concentrations measured arterial jugular venous samples twice day well microdialysisextracted brain extracellular fluid ecf following pooling every 6 h creactive protein level crp white blood cell count wbc temperature confirmed systemic clinical infection used systemic markers inflammation principal component analyses linear mixedeffect models crosscorrelations multiple factor analyses usedresultsjugular arterial blood held similar cytokine information content brainecf markedly different clear arterial jugular gradient seen substantial delayed temporal associations blood brain compartments detected development systemic clinical infection resulted significant decrease il1ra gcsf pdgfabbb mip1b rantes p 005 respectively brainecf even adjusting injury severity demographic factors increase several cytokines seen arterial bloodconclusionssystemic inflammation infection particular alters cytokine levels different patterns seen brain blood cerebral inflammatory monitoring provides independent information arterial jugular samples demonstrate similar information content findings present potential new treatment options severe tbi patients novel prospective trials warranted confirm associationsgraphical abstract,0.0
measuring advance care planning behavior dutch adults translation cultural adaptation validation advance care planning engagement survey background advance care planning acp enables people define discuss record preferences treatment care measures acp behavior lacking netherlands aimed translate culturally adapt validate 34item acp engagement survey dutchmethodsfollowing validation guidelines tested content validity internal consistency reproducibility construct validity interpretability criterion validity among persons without chronic diseaseresultsforwardbackward translation indicated need minor adaptations two hundred thirtytwo persons completed baseline retest surveys 121 aged 60 years persons chronic disease n 151 considered survey valuable without 66 vs 59 p 0001 scale 20100 indicating good content validity internal consistency cronbachs alpha 097 reproducibility intraclass correlation 088 good total acp engagement higher among persons chronic disease without 29 vs 24 p 001 scale 1 5 indicating good psychometric support construct validity interpretability positive correlations acp engagement survey general selfefficacy survey indicated good criterion validity p 005 conclusionsthis study provided good psychometric support validity reliability dutch 34item acp engagement survey instrument can used assess involvement acp adults without chronic disease,0.0
transplantation mesenchymal stem cells ameliorates systemic lupus erythematosus upregulates b10 cells tgf1 background considerable experimental clinical evidences proved human umbilical cord mesenchymal stem cells ucmscs transplantation powerful systemic lupus erythematosus sle treatment mscs upregulate regulatory b cells bregs mice model immune disease however regulation mscs bregs sle environment remains unclearmethodsto assess abilities ucmscs treat sle mscs transferred intravenously 17 18weekold mrl lpr mice four weeks later mice sacrificed survival rates antidsdna antibodies renal histology evaluated cd4+ t helper th cell subgroups interleukin il 10+ bregs b10 spleen quantitated flow cytometry changes transforming growth factor tgf 1 il6 indoleamine 2 3dioxyenase ido mrnas expressed mscs cocultured b cells detected using realtime polymerase chain reaction rtpcr mscs infected lentivirus carrying tgf1 shrnas mscs low expression tgf1 conducted coculture vitro transplantation experiments vivoresultsucmscs transplantation efficiently downregulate 24 h proteinuria antidsdna antibodies correct treg th17 th1 imbalances increase frequency b10 cells expression tgf1 mscs significantly increased coculture b cells downregulation tgf1 mscs significantly attenuate upregulation b10 mscs vitro vivo downregulation tgf1 also compromised immunomodulation effects mscs th17 treg cells therapeutic effects msc transplantationconclusionsucmscs protect sle mice upregulate il10+ bregs via tgf1,1.0
association lewy bodies limbicpredominant agerelated tdp43 encephalopathy neuropathologic changes role cognition alzheimers dementia older persons abstractlewy bodies lbs limbicpredominant agerelated tdp43 encephalopathy neuropathologic change latenc common older persons associated cognitive impairment however little known relationship lbs latenc combined roles cognitive impairment alzheimers dementia communitydwelling participants study included 1670 communitybased participants mean ageatdeath 895 years sd 665 69 females underwent annual assessments cognition create summary measures global cognition cognitive domains evaluation alzheimers dementia systematic neuropathologic evaluations performed assess lbs latenc alzheimers disease ad pathology excluded cases pathologically confirmed frontotemporal lobar degeneration study logistic linear regression analyses used adjusted demographics ad pathology lbs present 428 256 decedents 29 nigrapredominant 165 limbictype 234 neocorticaltype 865 517 decedents exhibited latenc 307 stage 1 167 stage 2 391 stage 3 lbs combined latenc common 15 participants alzheimers dementia 25 neocorticaltype nigralpredominant limbictype lbs increased odds stage 2 3 latenc odds ratio 170 95 confidence interval 126230 association neocorticaltype lbs stage 2 3 latenc stronger 90 years age women analyses cognition alzheimers dementia latenc neocorticaltype lbs separately related lower global cognition five specific cognitive domains increased odds alzheimers dementia beyond ad pathology limbictype lbs related lower global cognition domains episodic working semantic memory increased odds alzheimers dementia furthermore interaction limbic neocorticaltype lbs latenc cognitive function cognitive domains alzheimers dementia findings suggest neocorticaltype lbs associated latenc specifically younger old women limbic neocorticaltype lbs latenc separate additive effects cognitive function odds alzheimers dementia,0.0
viability msqol54 general healthrelated quality life score using bifactor model health qual life outcomes 2021 sep 25 19 1 224 doi 101186 s1295502101857yabstractbackground msqol54 multidimensional widelyused healthrelated quality life hrqol instrument specific multiple sclerosis ms findings validation study suggested two msqol54 composite scores correlated given correlation assumed unique total score hrqol may calculated advantage provide key stakeholders single overall hrqol score aimed assess well bifactor model account msqol54 structure order verify whether total hrqol score can calculatedmethods large international database 3669 ms patients used means confirmatory factor analysis estimated bifactor model every item loads onto general factor group factor fit bifactor model compared single two secondorder factor models means akaike information bayesian information criteria reduction reliability total subscale scores evaluated mc donalds coefficients omega omega hierarchical results bifactor model outperformed two secondorder factor models statistics items loaded satisfactorily 040 general hrqol factor except sexual function items omega coefficients total score satisfactory 098 087 omega hierarchical subscales ranged 022 057 except sexual function 070 conclusions bifactor model particularly useful intended acknowledge multidimensionality time take account single general construct hrqol related ms total raw score can used estimate general hrqol latent scorepmid34563229 doi101186 s1295502101857y,0.0
uk variance dmt advice prescribing ms pregnancy impact uk consensus pregnancy multiple sclerosis abn guidelines abstractbackgroundthe abn multiple sclerosis ms pregnancy guidelines set combine best current evidence expert consensus developed provide practical framework support neurologists counselling women ms regarding pregnancy key objective reduce variation practice increase clarity patients area uncertaintymethodsin order assess impact guidelines practice assess ongoing areas need conducted online survey ms pregnancy survey cascaded via email uk neurologists december 2019 january 2020 individuals completed questionnaire anonymouslyresultsthe majority respondents reported changing prescribing practice interferonbeta preparations ifnb natalizumab abn guidelines commonly cited reason change 76 however considerable variation advice regarding use dmts pregnancyconclusionsthere substantial variation advice given women ms around pregnancy reflected prescribing practice uk neurologists awareness national guidelines good driven change majority ms neurologists remains need continually update communicate guidelines particularly recommendations evolve increasing evidence,0.0
cholesteryl ester transfer protein cetp drug target cardiovascular disease nat commun 2021 sep 24 12 1 5640 doi 101038 s41467021257033abstractdevelopment cholesteryl ester transfer protein cetp inhibitors coronary heart disease chd yet deliver licensed medicines distinguish compound drug target failure compared evidence clinical trials drug target mendelian randomization cetp protein concentration comparing mendelian randomization proprotein convertase subtilisin kexin type 9 pcsk9 show previous failures cetp inhibitors likely compound related illustrated significant degrees betweencompound heterogeneity effects lipids blood pressure clinical outcomes observed trials ontarget cetp inhibition assessed mendelian randomization expected reduce risk chd heart failure diabetes chronic kidney disease increasing risk agerelated macular degeneration contrast lower pcsk9 concentration anticipated decrease risk chd heart failure atrial fibrillation chronic kidney disease multiple sclerosis stroke potentially increasing risk alzheimers disease asthma due distinct effects lipoprotein metabolite profiles joint inhibition cetp pcsk9 may provide added benefit conclusion provide genetic evidence cetp effective target chd prevention potential ontarget adverse effect agerelated macular degenerationpmid34561430 doi101038 s41467021257033,0.0
development humoral cellular immunological memory sarscov2 despite bcell depleting treatment multiple sclerosis iscience 2021 sep 2103078 doi 101016 jisci2021103078 online ahead printabstractbcell depleting therapies bcdts widely used immunomodulating agents autoimmune diseases multiple sclerosis possible impact development immunity sarscov2 raised concerns covid19 pandemic evaluated frequency covid19like symptoms determined immunological responses participants observational trial comprising several multiple sclerosis disease modulatory drugs combatms nct03193866 eleven patients vaccination focus bcdt almost seropositive 179 seronegative patients bcdt enriched history covid19like symptoms developed antisarscov2 tcell memory tcells displayed functional similarity controls producing ifn tnf following vaccination vaccinespecific humoral memory impaired patients developed specific tcell response results indicate bcdts abrogate sarscov2 cellular memory provide possible explanation majority patients bcdts recover covid19pmid34490414 pmcpmc8410640 doi101016 jisci2021103078,0.0
cerebrospinal fluid levels neurotrophic factor neuroleukin increased early alzheimers disease cerebral amyloid angiopathy background neuroleukin nlk protein neurotrophic properties present proportion senile plaques amyloid laden vessels suggested nlk part neuroprotective response amyloid induced cell death aim study investigate value cerebrospinal fluid csf nlk levels biomarker vascular amyloid deposition patients cerebral amyloid angiopathy caa patients amnestic mild cognitive impairment amci alzheimers disease ad methodscsf nlk levels quantified elisa caa patients n 25 controls n 27 two independent samples amci patients ad patients controls 1 radboud university medical center nijmegen included n 19 amci patients n 40 ad patients n 32 controls 2 hospital sant pau barcelona included n 33 amci patients n 17 ad patients n 50 controlsresultscsf nlk levels similar caa patients controls p 095 however found elevated csf concentration nlk amci p 00001 ad patients p 00001 compared controls samples sets addition found correlation csf nlk csf ykl40 ageadjustedspearmanrankcoefficient 082 p 00001 amci ad patients wellknown glial marker neuroinflammationconclusionswe found csf nlk levels elevated amci ad patients compared controls increased caa patients csf nlk levels may related increased neuroinflammatory state early stages ad given association ykl40,1.0
nfl predicts relapsefree progression longitudinal multiple sclerosis cohort study abstractbackgroundeasily accessible biomarkers enabling identification patients multiple sclerosis ms will accumulate irreversible disability long term essential guide early therapeutic decisions examine utility serum neurofilament light chain snfl forecasting relapsefree disability progression conversion secondary progressive ms spms prospective neurofilament longterm outcome ms naloms cohortmethodsthe predictive ability snfl baseline snfl followup fu baseline bl ratio regard disability progression assessed within development cohort naloms n196 patients relapsingremitting ms rrms clinically isolated syndrome validated external independent cohort dsseldorf essen n204 relapsefree edssprogression rfp inflammatoryindependent edssincrease 12 months prior fu spmstransition minimum edssscore 30 investigatedfindingsduring study period 17 n34 naloms patients suffered rfp 14 n27 converted spms fu validation cohort rfp n42 spmsconversion n24 snfl bl increased patients rfp 108 pg ml interquartile range iqr 77150 vs 72 pg ml 45125 p0017 multivariable logistic regression model increased snfl levels bl odds ratio 102 95 confidence interval ci 101104 p0012 remained independent risk factor rfp predicted individual rfp risk accuracy 82 naloms 83 validation cohort revealed support vector machine addition snfl fu bl ratio increased spmsconverters 116 089170 vs 096 075123 p0011 confirmed multivariable logistic regression model snfl fu bl ratio remained model 1476 95ci 10782 019 p0015 individual snfl fu bl ratios showed predictive accuracy 72 naloms 63 validation cohort revealed machine learninginterpretationsnfl levels baseline predict relapsefree disability progression prospective longitudinal cohort study 6 years later prediction confirmed independent cohort snfl discriminates patients spms followup supports early identification patients risk later spms conversionfundingthis work supported german research council crctr128 else krner fresenius foundation hertiestiftung,0.0
microglia neuroinflammation neurodegeneration understanding therapy front neurosci 2021 sep 24 15742065 doi 103389 fnins2021742065 ecollection 2021abstractmicroglia resident macrophages central nervous system cns acting first line defense brain phagocytosing harmful pathogens cellular debris microglia emerge early erythromyeloid progenitors yolk sac enter developing brain establishment fully mature bloodbrain barrier physiological conditions brain development microglia contribute cns homeostasis supporting cell proliferation neural precursors postnatal life cells contribute preserving integrity neuronal circuits sculpting synapses cns injury microglia change morphology downregulate genes supporting homeostatic functions however still unclear whether changes accompanied molecular functional modifications might contribute pathological process comprehensive transcriptome analyses singlecell level identified specific gene perturbations occurring pathological microglia still precise protective detrimental role microglia neurological disorders far fully elucidated review results far obtained regarding role microglia neurodegenerative disorders will discussed solid sound evidence suggesting regulating microglia functions disease pathology might represent strategy develop future therapies aimed counteracting brain degeneration multiple sclerosis alzheimers disease parkinsons disease amyotrophic lateral sclerosispmid34630027 pmcpmc8497816 doi103389 fnins2021742065,0.0
investigating shared genetic architecture multiple sclerosis inflammatory bowel diseases nat commun 2021 sep 24 12 1 5641 doi 101038 s41467021257680abstractan epidemiological association multiple sclerosis ms inflammatory bowel disease ibd well established whether reflects shared genetic aetiology whether consistent genetic relationships exist ms two predominant ibd subtypes ulcerative colitis uc crohns disease cd remains unclear use largescale genomewide association study summary data investigate shared genetic architecture ms ibd overall uc cd independently find significantly greater genetic correlation ms uc ms cd identify three snps shared ms ibd rs13428812 uc rs116555563 cd rs13428812 rs9977672 crosstrait metaanalyses find suggestive evidence causal effect ms uc ibd using mendelian randomization weak inconsistent evidence causal effect ibd uc ms observe largely consistent patterns tissuespecific heritability enrichment ms ibds lung spleen whole blood small intestine identify celltypespecific enrichment ms ibds cd4+ t cells lung cd8+ cytotoxic t cells lung spleen study sheds light biological basis comorbidity ms ibdpmid34561436 doi101038 s41467021257680,0.0
role complement synaptic pruning neurodegeneration immunotargets ther 2021 sep 24 10373386 doi 102147 itts305420 ecollection 2021abstractthe complement system essential part innate immune system composed group secreted membrane proteins collectively participate maintaining function healthy diseased brain however inappropriate activation complement system related inflammatory response multiple diseases stroke traumatic brain injury multiple sclerosis alzheimers disease well zika infection radiotherapy addition c1q c3 initial activation components complement cascade shown play key beneficial role refinement synaptic circuits developmental stages adult plasticity nevertheless excessive synaptic pruning adult brain can detrimental associated synaptic loss several pathological conditions brief review will discuss role complement system synaptic pruning well contribution neurodegeneration cognitive deficits also mention potential therapeutic approaches target complement system treat several neuroinflammatory diseases unintended consequences radiotherapypmid34595138 pmcpmc8478425 doi102147 itts305420,0.0
risk covid19 survivors domestic violence abuse abstracta shadow pandemic domestic violence abuse dva emerged secondary strict public health measures containing spread sarscov2 many countries implemented policies allow free movement dva survivors attempts minimise exposure abusive environments although policies well received result possibility increased covid19 transmission within vulnerable group currently prioritised vaccination therefore aimed compare risk developing suspected confirmed covid19 women aged 16 years exposed dva agesexmatched unexposed controls following adjustment known covid19 risk factors populationbased retrospective open cohort study undertaken 31 january 2020 28 february 2021 using health improvement network database identified 10 462 eligible women exposed dva matched 41 467 similarly aged unexposed women following adjustment key covariates women exposed dva increased risk ahr 157 95 ci 129190 suspected confirmed covid19 compared unexposed women findings support previous calls positive policy action improving dva surveillance prioritising survivors covid19 vaccination,0.0
association chronic periodontitis risk alzheimers disease combination text mining geo dataset background although chronic periodontitis previously reported linked alzheimers disease ad pathogenesis two unclear purpose study analyze screen relevant promising molecular markers chronic periodontitis alzheimers disease ad methodsin paper analyzed three ad expression datasets extracted differentially expressed genes degs intersected chronic periodontitis genes obtained text mining finally obtained integrated degs followed enriching matching matching cell signal cascade david analysis moreover mcode cytoscape software employed uncover proteinprotein interaction ppi network matching hub gene finally verified data using different independent ad cohortresultsthe chronic periodontitis gene set acquired text abstracting intersected previously obtained three ad groups 12 common genes obtained functional enrichment assessment uncovered 12 crossgenes mainly linked cell morphogenesis involved neuron differentiation leading edge membrane receptor ligand activity ppi network creation ten hub genes linked ad retrieved consisting spp1 thy1 cd44 itgb1 hspb3 creb1 sst uchl1 ccl5 bmp7 finally function terms new independent dataset used verify previous dataset found 22 go terms one pathway ecmreceptor interaction pathways overlapping functional termsconclusionsthe establishment abovementioned candidate key genes well enriched signaling cascades provides promising molecular markers chronic periodontitisrelated ad may help diagnosis treatment ad patients future,0.0
familial multiple sclerosis mother son pair sri lankan south asian first case rep neurol med 2021 sep 23 20211172870 doi 101155 2021 1172870 ecollection 2021abstractmultiple sclerosis ms immunemediated demyelinating disorder involving central nervous system cns common amongst young females although exact cause ms yet unknown viral infections ebv environmental factors autoimmune genetic mechanisms involving hladrb1 loci implicated familial ms reported geographic locations ethnic groups thought rare asia paper present sri lankan mother son clinically definite ms conforming mcdonalds 2017 clinical magnims 2016 radiological criteria oligoclonal bands csf ocbief serum bands indicating intrathecal production negative aqp4 mog igg serology familial ms common among siblings sistersister relationship highest rate lowest relation amongst fatherson motherson pairs amongst siblings risk ms 35 47 inherited factors rather common environmental exposure influence susceptibility cases best knowledge ms occurring motherson pair reported either sri lanka south asiapmid34603807 pmcpmc8486554 doi101155 2021 1172870,1.0
vitro antioxidant activity crude extracts harpagophytum zeyheri antiinflammatory cytotoxicity activity compared diclofenac background study evaluated vitro antioxidant activity comparison antiinflammatory cytotoxic activity harpagopytum zeyheri diclofenacmethodsin vitro assays conducted using water ethanol ethyl acetate extracts hzeyheri antioxidant activity evaluated using 2 2diphenyl1picrylhydrazy dpph 2 2 azinobis 3ethylbenzothiazoline6sulphonic acid abts assays antiinflammatory activity determined measuring inhibition nitric oxide lipopolysaccharide lps induced raw 2647 mouse macrophages well cytokine tnf il10 expression lpsinduced u937 human macrophages cytotoxicity cell viability determined using 3 4 5dimethylthiazol 2yl 2 5diphenyl tetrazolium bromide mtt assayresultsthe ethyl acetate extract lowest ic50 values dpph 591 g ml abts 205 g ml assay compared extracts furthermore ethyl acetate extracts effectively inhibited tnf proved comparable diclofenac concentrations extracts h zeyheri displayed dosedependent activity associated low levels humanil10 expression compared quercetin furthermore extracts displayed low toxicity relative diclofenacconclusionsthese findings show h zeyheri significant antioxidant activity additionally similarities exist inflammatory activity h zeyheri diclofenac concentrations well low toxicity comparison diclofenac,0.0
genomeoriented treatment strategies autoimmune diseases autoimmune diseases defined conditions various organs damaged activated autoreactive t cells involved failure immune tolerance autoantibodies produced b cells organspecific autoimmune diseases including ulcerative colitis hashimotos thyroiditis multiple sclerosis systemic autoimmune diseases affect damage multiple organs skin joints heart kidneys serosa nerves blood vessels also referred connective tissue diseases rheumatoid arthritis typical systemic autoimmune disease affecting patients specific autoantigens identified 1 2 3 various diseasesusceptibility genes identified including hladrb1 ptpn22 ctla4 stat4 tnfaip3 ccl21 padi4 established genes combined environmental factors epigenetically modified citrullination extracellular matrix molecules filaggrin fibrinogen immune tolerance antigens fails thereby inducing autoimmunity activated lymphocytes produce inflammatory cytokines tumor necrosis factor tnf interleukin il 6 cause inflammation multiple organs including joints irreversible structural damage joints due prolonged inflammation multiorgan disorders lung joint injury progresses soon onset deformed joints cause irreversible physical dysfunction therefore prompt appropriate diagnosis treatment necessaryin 20th century corticosteroids nonsteroidal antiinflammatory drugs used relieve pain swelling multiple joints however drugs control progression joint destruction consequent issue treatment control endocrine metabolic adverse drug reactions longterm use corticosteroids infection associated susceptibility infection due immunosuppression 21st century advent drugs targeting important molecules involved pathogenesis rheumatoid arthritis brought paradigm shift treatment addition conventional synthetic antirheumatic drugs methotrexate several new drugs developed include biological antirheumatic drugs purified biological drugs target tnf il6 t cell costimulation molecule cd28 others targeted synthetic antirheumatic drugs janus kinase inhibitors involved signal transduction cytokines others clinical remission become realistic therapeutic goal patients maintenance remission allowed prevention structural joint damage control progression physical dysfunction long period 1 2 3 drugs approved treating rheumatoid arthritis used treat many autoimmune diseasessystemic lupus erythematosus sle typical systemic autoimmune disease commonly occurs women childbearing age affects systemic organs skin joints kidneys serosa nerves heart blood vessels manifests various clinical symptoms past nonspecific treatment corticosteroids immunosuppressants drugs applied suppress immune abnormalities prevent progression organ dysfunction although drugs improved prognosis disease longterm use causes various adverse reactions particular severe opportunistic infections associated susceptibility infection due immunosuppression leading causes death disease development molecular target drugs also attempted disease main pathological characteristics activation b cells production autoantibodies due autoimmune abnormalities 4 5 6 b cells stimulated t follicular helper cells autoreactive t cells undergo class switching differentiate antibody autoantibodyproducing cells addition b cells express major histocompatibility complex molecules function antigenpresenting cells t cells immune cells furthermore b cells stimulated immune system produce various cytokines words b cells play central role responders stimulators immune system autoimmune pathology thus b celltargeting therapy expected mainstay treatment sle however treatment b celltargeting biological drugs rituximab epratuzumab successful date contrast many diseasesusceptibility genes sle identified genomewide association analysis exist b cells 6 7 suggests disease associated abnormalities adaptive immune systemhowever irf5 irak1 tlr7 central genes innate immune system served mainly dendritic cells also identified diseasesusceptibility genes sle patients sle dendritic cells highly express tolllike receptors bind stimuli dna rna released apoptosis necrosis activate innate immune system different cytokines produced dendritic cells type interferon ifn soluble b cellactivating factor baff il12 il23 chemokines induce differentiation activation b t cells adaptive immune system several successful outcomes achieved biological drugs targeting cytokines soluble baff type ifn produced dendritic cells bridge innate adaptive immune systems finding important implications 5 6 7 8 can also regarded good example genomewide association analysis provides new understanding pathology new treatment concepts sle drugs targeting molecules involved pathogenesis insufficient suggesting disease treated without developing therapeutic approach based genomic data fujio et al suggested review transcriptome transomics analysis systemic lupus erythematosus comprehensive analysis multilevel omics data individual molecules also genome epigenome transcriptome proteome metabolome etc words multiomics transomics analyses lead elucidation new pathological conditions discovery new therapeutic targets sle 9 approaches also applicable autoimmune diseases roles cytotoxic lymphocytes mic lilr families pathophysiology takayasu arteritis yoshifuji terao reviewed potential new therapeutic targets identified takayasu arteritis genome analysis 10 updates genetics systemic sclerosis ota kuwana explain new understanding based genome analysis pathology systemic sclerosis moreover despite dramatic advances treatment rheumatoid arthritis differentiation use many molecular target drugs unknown 11 genomicsdriven drug discovery based disease susceptibility genes sonehara okada mention differential use molecular target drugs rheumatoid arthritis based genome analysis introduction precision medicine using molecular target therapy lead efficient treatment reduce health care costs alleviate adverse events feature issue presents latest findings autoimmune diseases worldleading researchers genomic medical studies 12 using genomics multiomics transomics data fullest extent will bring new paradigm shift treating autoimmune diseases regarded intractable new fledgling trend may develop extensively various studies near future,0.0
cognitive assessments patients neurological conditions preliminary survey speechlanguage pathology practice patterns j speech lang pathol 2021 jul 19112 doi 101044 2021_ajslp2000187 online ahead printabstractpurpose speechlanguage pathologists slps often responsible assessing cognitive disorders affect communication individuals diagnosed suspected acute degenerative neurological conditions however consensus appropriate assessment tools various neurological disorders remains elusive preliminary survey conducted study current practices use published unpublished tools slps assessing cognitivecommunication impairments across common neurologic conditions method 18item webbased survey sent slps asha communities social media asking select cognitive assessment tools use evaluate cognitivecommunication status individuals parkinsons disease multiple sclerosis dementia stroke ie cerebrovascular accident traumatic brain injury 100 slps completed online survey represent spectrum professionals seeing neurologic patients across united states results among 100 responding slps unique pattern assessment tool use noted across neurologic disorders indicated chisquare analysis common set nonstandardized observational assessment practices reported commonly regardless neurologic condition conclusions study shows consistent cognitive assessment practices slps across various neurological conditions rather unique protocols relevant patterns typical across disorders however amount clinical evaluations supported informal observation completion select subtests standardized assessment tools considerable preliminary information conflicts principles rigorous assessment increases risk erroneous findings identifying cognitive impairments research decisionmaking process clinician assessment selection warranted encourage consistent evidencebased practice persons cognitive impairments better recognition limitations imposed providing clinical services impact reliability validity cognitive assessments can drive future clinical practice policy practice recommendationspmid34280040 doi101044 2021_ajslp2000187,0.0
expanding availability speechgenerating device evaluation treatment people amyotrophic lateral sclerosis pals telepractice perspectives pals communication partners j speech lang pathol 2021 aug 19117 doi 101044 2021_ajslp2000334 online ahead printabstractpurpose examine experiences people als pals communication partners cals regarding receiving speechgenerating device sgd evaluation treatment via telepractice method eight pals along primary cals participated telepractice sgd evaluation treatment augmentative alternative communication aac specialist representatives multiple sgd vendors participants interviewed postevaluation postsgd training examine experiences mixed methods data collected likert scale responses qualitative interviews results telepractice sgd evaluation training feasible resulted pals receiving sgds able use communicate likert rating items qualitative interviews participants rated telepractice experience highly terms giving access aac services via aac specialist otherwise able access format possible given limitations mobility endurance caregiver availability suggestions improving telepractice experience provided conclusions telepractice considered option provide vital sgd services patients geographically remote mobility impaired unable leave home experience fatigue travel otherwise access specialized services telepractice allows patients preserve time energy assessment treatment sessions resulting perhaps deeper frequent engagement evaluation training telepractice serve alternative outpatient inperson evaluations utilized conjunction inperson appointments supplemental material https doiorg 1023641 asha15094257pmid34411491 doi101044 2021_ajslp2000334,0.0
examining clinical utility selected memorybased embedded performance validity tests neuropsychological assessment patients multiple sclerosis neurol int 2021 sep 23 13 4 477486 doi 103390 neurolint13040047abstractwithin neuropsychological assessment clinicians responsible ensuring validity obtained cognitive data increased attention paid performance validity patients multiple sclerosis pwms experts proposed batteries neuropsychological tests use population though none contain recommendations standalone performance validity tests pvts california verbal learning test second edition cvltii brief visuospatial memory test revised bvmtr included aforementioned recommended neuropsychological batteriesinclude previously validated embedded pvts offer advantages including expedience reduced costs prior work exploring utility pwms purpose present study determine potential clinical utility embedded pvts detect signal noncredibility operationally defined criterion standalone pvt performance one hundred thirtythree 133 patients m age 4828 767 women 850 white ms referred neuropsychological assessment large midwestern academic medical center patients placed credible n 100 noncredible n 33 groups based standalone pvt criterion classification statistics four cvltii bvmtr pvts interest isolation poor aucs 058062 several arithmetic logistic regressionderived multivariate formulas calculated similarly demonstrated poor discriminability aucs 061064 although embedded pvts may arguably maximize efficiency minimize test burden pwms common ones cvltii bvmtr may psychometrically appropriate sufficiently sensitive substitutable standalone pvts population clinical neuropsychologists evaluate patients encouraged include standalone pvts assessment batteries ensure clinical care conclusions drawn neuropsychological data validpmid34698256 doi103390 neurolint13040047,0.0
meningitis retention syndrome caused varicella zoster virus patient without rash case report background meningitis retention syndrome mrs rare condition presents acute urinary retention complication aseptic meningitis cases mrs due varicella zoster virus vzv infection without rash rare report case patient signs meningitis vzv infection including rashcase presentationa 58yearold man presented dysesthesia lower limbs acute urinary retention fever rash signs meningitis diagnosed vzv infection based detection vzv dna cerebrospinal fluid responded satisfactorily course intravenous acyclovir experienced sequelae 2year followup periodconclusionmrs due aseptic meningitis viral origin considered differential diagnosis acute urinary retention even absence specific signs symptoms meningitis suggestive rash,0.0
serious game design clinical improvement physical rehabilitation systematic review jmir serious games 2021 sep 23 9 3 e20066 doi 102196 20066abstractbackground serious video games now used assessed clinical protocols several studies reporting patient improvement engagement type therapy even though literature reviews approached topic game perspective presented broad overview types video games used context still need better understand different game characteristics development strategies might impact relate clinical outcomesobjective review assessed relationship characteristics serious games sgs relationship clinical outcomes studies use type therapy motor impairment rehabilitation patients stroke multiple sclerosis cerebral palsy purpose take closer look video game design features described literature game genre gg game nature gn game development strategy gds assess may contribute toward improving health outcomes additionally review attempted bring together medical game development perspectives facilitate communication clinicians game developers therefore easing process choosing video games used physical rehabilitationmethods analyzed main features sg design obtain significant clinical outcomes applied physical rehabilitation patients recovering motor impairments resulting stroke multiple sclerosis cerebral palsy implemented prisma preferred reporting items systematic reviews metaanalyses databaseadjusted electronic search strategy pubmed ieee xplore cochrane databasesresults screened 623 related papers 20102021 identified 12 presented results compatible inclusion criteria total 512 participants stroke 8 studies 417 participants cerebral palsy 1 study 8 participants multiple sclerosis 2 studies 46 participants included 1 study targeting elderly 41 participants also included studies assessed motor sensory functional functions also measured general health outcomes interventions games used upperlimb motor rehabilitation 12 studies 8 presented significant improvements least one clinical measurement 6 presented games casual gg 1 combined casual simulation exergaming ggs 2 combined sports simulation ggsconclusions possible combinations game design features gg gn gds described custommade casual games resort firstperson perspective feature visible player character played singleplayer mode use nonimmersive virtual reality attain best results terms positive clinical outcomes addition use custommade games versus commercial offtheshelf games tends give better clinical results although latter perceived motivating engagingpmid34554102 doi102196 20066,0.0
leveraging highresolution 7tesla mri derive quantitative metrics trigeminal nerve subnuclei limbic structures trigeminal neuralgia background trigeminal neuralgia tn chronic neurological disease strongly associated neurovascular compression nvc trigeminal nerve near root entry zone trigeminal nerve site nvc extensively studied limbic structures potentially involved tn adequately characterized specifically hippocampus stresssensitive region may structurally impacted chronic tn pain center emotionrelated network amygdala closely related stress regulation may associated tn pain well thalamus involved trigeminal sensory pathway nociception may play role pain processing tn objective study assess structural alterations trigeminal nerve subregions hippocampus amygdala thalamus tn patients using ultrahigh field mri examine quantitative differences structures compared healthy controlsmethodsthirteen tn patients 13 matched controls scanned 7tesla mri high resolution t1weighted imaging nerve cross sectional area csa measured automated algorithm used segment hippocampal amygdaloid thalamic subregions nerve csa limbic structure subnuclei volumes compared tn patients controlsresultscsa posterior cisternal nerve symptomatic side smaller patients 375 mm2 compared sidematched controls 577 mm2 p 0006 tn patients basal subnucleus amygdala volume 0347 mm3 reduced symptomatic side compared controls 0401 mm3 p 0025 paralaminar subnucleus volume 004 mm3 also reduced symptomatic side compared controls 005 mm3 p 0009 central lateral thalamic subnucleus larger tn patients symptomatic side 0033 mm3 asymptomatic side 0035 mm3 compared corresponding sides controls 0025 mm3 sides p 0048 p 0003 respectively inferior lateral pulvinar thalamic subnuclei reduced tn patients symptomatic side 02 mm3 017 mm3 respectively compared controls 023 mm3 p 004 018 mm3 p 004 respectively significant findings found hippocampal subfields analyzedconclusionsthese findings generated highly sensitive 7 t mri protocol provide compelling support theory tn neurobiology complex amalgamation local structural changes within trigeminal nerve structural alterations subnuclei limbic structures directly indirectly involved nociception pain processing,0.0
prevalence risk factors chronic kidney disease hiv positive mexican cohort background hiv subjects several kidney pathologies like hivassociated nephropathy antiretroviral therapy injury among others global prevalence chronic kidney disease ckd 816 however hiv subjects prevalence varies geographic regions 238 aim determine prevalence ckd identify associated risk factorsmethodsa longitudinal descriptive study carried hospital civil de guadalajara feb18 jan19 basal clinical demographic opportunistic infections oi laboratory data obtained months 0 3 inclusion criteria 18 years old nave hiv + urine albumin creatinine ratio serum creatinine urine test signed informed consent descriptive multiple logistic regression statistical analyses maderesultsone hundred twenty subjects included 925 male 33 95 years 60 consumed tobacco 73 alcohol 59 type drug ckd prevalence 158 ckd patients higher risk hepatitis c virus coinfection relative risk rr 59 hcv infection rr43 30 years old rr39 c clinicalstage rr35 cd4+ t cells count 200 cells l rr 24 hiv1 viral load 100 000 cop ml rr 27conclusionsour study showed higher ckd prevalence patients hiv higher ckd development coinfections hepatitis c virus mycobacterium tuberculosis identification prompt management ckd coinfections considered avoid progression delay renal replacement therapy long possible,0.0
synthesis characterization stresstesting robust quillaja saponin stabilized oilinwater phytocannabinoid nanoemulsion background study describes design optimization stresstesting novel phytocannabinoid nanoemulsion generated using highpressure homogenization text qnaturale circledr plantderived commercial emulsifier containing quillaja saponin used stabilize lipid phase droplets water stresstesting performed nanoemulsion order evaluate chemical colloidal stability influence different environmental factors encompassing physical chemical stressorsmethodsextensive optimization studies conducted arrive ideal nanoemulsion formulation coarse emulsion containing 166 wt cbdenriched cannabis distillate 834 wt carrier soybean oil dispersed 10 wt text qnaturale circledr 15 wt quillaja saponin solution 10 homogenization cycles pressure 30 000 psi produced stable nanoemulsion nanoemulsion subjected stress studiesresultsthe optimized nanoemulsion average droplet diameter ca 120 nm average droplet surface potentials ca 30 mv imaged characterized variety protocols proved stable droplet agglomeration phase separation upon storage ambient conditions 6 weeks well variety physical stressors heat cold dilution carbonation ph values 2 moderately high salt concentrations 100 mm however destabilized nanoemulsion eventually leading phase separation cannabis potency determined hplc detrimentally affected changes nanoemulsion phase stabilityconclusionsquillaja saponin stabilized cannabidiol cbd enriched nanoemulsions stable robust systems even low emulsifier concentrations therefore significant scientific well commercial perspective,0.0
calcitriol confers neuroprotective effects traumatic brain injury activating nrf2 signaling autophagymediated mechanism background present study aimed explore potential interaction oxidative stress autophagy progression traumatic brain injury tbi therapeutic mechanism calcitriol active form vitamin d vitd methodsneuroprotective effects calcitriol examined following tbi evaluated impacts tbi calcitriol treatment autophagic process nuclear factor e2related factor 2 nrf2 signalingresultswe found treatment calcitriol markedly ameliorated neurological deficits histopathological changes following tbi brain damage impaired autophagic flux impeded nrf2 signaling major regulator antioxidant response consequently leading uncontrolled excessive oxidative stress meanwhile calcitriol promoted autophagic process activated nrf2 signaling evidenced reduced keap1 expression enhanced nrf2 translocation thereby mitigating tbiinduced oxidative damage support found chloroquine cq treatment abrogated calcitriolinduced autophagy compromised nrf2 activation increased keap1 accumulation reduced expression nrf2targeted genes additionally cq treatment nrf2 genetic knockout abolished protective effects calcitriol tbiinduced neurological deficits neuronal apoptosisconclusionstherefore work demonstrated neuroprotective role calcitriol tbi triggering nrf2 activation might mediated autophagy,1.0
kv13 channel upregulation peripheral blood t lymphocytes patients multiple sclerosis front pharmacol 2021 sep 23 12714841 doi 103389 fphar2021714841 ecollection 2021abstractvoltagegated kv13 potassium channels key regulators t lymphocyte activation proliferation cytokine production providing necessary membrane hyperpolarization calcium influx following immune stimulation noteworthy accumulating body vivo vitro evidence links channels multiple sclerosis pathophysiology studied electrophysiological properties transcriptional translational expression t lymphocyte kv13 channels multiple sclerosis combining patch clamp recordings reverse transcription polymerase chain reaction flow cytometry freshly isolated peripheral blood t lymphocytes two patient cohorts multiple sclerosis well healthy disease controls data demonstrate t lymphocytes ms manifest significant upregulation kv13 mrna kv13 membrane protein kv13 current density therefore functional membrane channel protein compared control groups p 0001 interestingly patient subgrouping shows kv13 channel density significantly higher secondary progressive compared relapsingremitting multiple sclerosis p 0001 taking account tight connection kv13 channel activity calciumdependent processes data predict partly explain reported alterations t lymphocyte function multiple sclerosis highlight kv13 channels potential therapeutic targets peripheral biomarkers diseasepmid34630091 pmcpmc8495199 doi103389 fphar2021714841,0.0
bhlhe40 promotes macrophage proinflammatory gene expression functions abstractmacrophages principal innate immune cells populate major organs provide first line cellular defense infections injuries immediate earlyresponding macrophages must mount robust proinflammatory response protect host eliminating deleterious agents effective proinflammatory macrophage response requires activation complex transcriptional programs modulate dynamic regulation inflammatory metabolic gene expression therefore transcription factors govern proinflammatory metabolic gene expression play essential role shaping macrophage inflammatory response herein identify basic helixloophelix family member e40 bhlhe40 critical transcription factor promotes broad proinflammatory glycolytic gene expression elevating hif1 levels macrophages vivo studies revealed myeloidbhlhe40 deficiency significantly attenuates macrophage neutrophil recruitment site inflammation integrated transcriptomics gene set enrichment analysis gsea studies show bhlhe40 deficiency broadly curtails inflammatory signaling pathways hypoxia response glycolytic gene expression macrophages utilizing complementary gain lossoffunction studies analyses uncovered bhlhe40 promotes lpsinduced hif1 mrna protein expression macrophages importantly forced overexpression oxygen stable form hif1 completely reversed attenuated proinflammatory glycolytic gene expression bhlhe40deficient macrophages collectively results demonstrate bhlhe40 promotes macrophage proinflammatory gene expression functions elevating hif1 expression macrophages,0.0
effect sarscov2 mrna vaccination ms patients treated disease modifying therapies abstractbackgroundin patients multiple sclerosis pwms diseasemodifying therapies dmts affects immune response antigens therefore postvaccination serological assessments needed evaluate effect vaccine sarscov2 antibody responsemethodswe designed prospective multicenter cohort study enrolling pwms scheduled sarscov2 vaccination mrna vaccines bnt162b2 pfizer biontech inc mrna1273 moderna tx inc blood collection first vaccine dose 4 weeks second dose planned centralized serological assessment electrochemiluminescence immunoassay eclia rochediagnostics logtransform antibody levels analyzed multivariable linear regressionfindings780 pwms 76 bnt162b2 24 mrna1273 pre 4week postvaccination blood assessments 87 112 untreated 154 197 ocrelizumab 25 32 rituximab 85 109 fingolimod 25 32 cladribine 404 517 dmts 677 patients 868 detectable postvaccination sarscov2 antibodies multivariable analysis antibody levels patients ocrelizumab 201fold decrease 95ci128317 p0001 fingolimod 26fold decrease 95ci1642 p0001 rituximab 20fold decrease 95ci1043 p0001 significantly reduced compared untreated patients vaccination mrna1273 resulted systematically 325fold higher antibody level 95ci246427 bnt162b2 vaccine p0001 antibody levels anticd20 therapies correlated time since last infusion rituximab longer intervals mean386 days ocrelizumab patients mean129 days interpretationin pwms anticd20 treatment fingolimod led reduced humoral response mrnabased sarscov2 vaccines mrna1273 elicits 325higher antibody levels bnt162b2 vaccine may preferentially considered patients anticd20 treatment fingolimod combining data cellular immune response vaccines including clinical followup will contribute better define appropriate sarscov2 vaccine strategies context dmts msfundingfism 2021 specialmulti 001 italian ministry healthprogetto z844a 51000,0.0
influence gut microbiome bcginduced trained immunity background bacillus calmettegurin bcg vaccine protects tuberculosis heterologous infections elicits high interindividual variation specific nonspecific trained immune responses gut microbiome increasingly recognized important modulator vaccine responses immunity general potential role bcginduced protection largely unknownresultsstool blood collected 321 healthy adults bcg vaccination followed blood sampling 2 weeks 3 months metagenomics based de novo genome assembly reveals 43 immunomodulatory taxa nonspecific trained immune response detected altered production cytokines il6 il1 tnf upon ex vivo blood restimulation staphylococcus aureus negatively correlates abundance roseburia specific response measured ifn production upon mycobacterium tuberculosis stimulation associated positively ruminococcus eggerthella lenta identified immunomodulatory taxa also strongest effects circulating metabolites roseburia affecting phenylalanine metabolism corroborated abundances relevant enzymes suggesting alternate phenylalanine metabolism modules activated roseburia speciesdependent mannerconclusionsvariability cytokine production bcg vaccination associated abundance microbial genomes turn affect produce metabolites circulation roseburia found alter trained immune responses phenylalanine metabolism revealing microbes microbial products may alter bcginduced immunity together findings contribute understanding specific trained immune responses bcg vaccination,0.0
identification factor xii contact activation site enables sensitive coagulation diagnostics nat commun 2021 sep 22 12 1 5596 doi 101038 s41467021258887abstractcontact activation refers process surfaceinduced activation factor xii fxii initiates blood coagulation captured activated partial thromboplastin time aptt assay show mechanism diagnostic implications fxii contact activation screening recombinant fxii mutants identified continuous stretch residues gln317ser339 essential fxii surface binding activation thrombin generation coagulation peptides spanning 23 residues competed surfaceinduced fxii activation although fxii mutants lacking residues gln317ser339 susceptible activation plasmin plasma kallikrein ineffective supporting arterial venous thrombus formation mice antibodies raised gln317ser339 region induced fxii activation triggered controllable contact activation solution leading thrombin generation intrinsic pathway coagulation antibodyactivated aptt allows standardization particulate aptt reagents sensitive monitoring coagulation factors viii ix xipmid34552086 doi101038 s41467021258887,0.0
single copy transgenic mutant fus strain reproduces agedependent als phenotypes c elegans micropubl biol 2021 sep 22 2021 doi 1017912 micropubbiology000473 ecollection 2021abstractmutations human dna rna binding protein fus associated amyotrophic lateral sclerosis frontotemporal lobar degeneration including aggressive juvenile onset forms cytoplasmic inclusions human fus proteins observed various neurodegenerative disorders huntingtons disease spinocerebellar ataxia suggesting fus proteinopathy may key player neurodegeneration better understand pathogenic mechanisms fus created single copy transgenic caenorhabditis elegans strains expressing fulllength untagged human fus worms gabaergic neurons transgenic worms expressing human mutant fus mfus display alsassociated phenotypes previous multiple copy transgenic model including adultonset agedependent loss motility progressive paralysis gabaergic neurodegeneration phenotypes distinct transgenic worms expressing human wildtype fus wtfus introduce c elegans single copy transgenic human mutant fus motor neuron toxicity may used rapid genetic pharmacological suppressor screeningpmid34568776 pmcpmc8459179 doi1017912 micropubbiology000473,0.0
kissing genetic ms risk loci life multiple sclerosis ms inflammatory autoimmune demyelinating disease central nervous system cns 1 debilitating effects sensory motor autonomic neurocognitive functions affect primarily young adults especially women two three times frequent men frequent northern countries affecting 150 individuals every 100 000 inhabitants eg canada scandinavian countries development often initially relapsing remitting later progressive disease associated genetic environmental risk factors 1 3 major histocompatibility complex mhc class il gene locus far prominent genetic risk factor altered immune responses epstein barr virus ebv causative infectious agent cases infectious mononucleosis kissing disease recent years emerged prominent environment induced risk factors ms 1 interestingly particularly infectious mononucleosis symptomatic primary ebv infection caused lymphocytosis mainly lytic ebv antigen specific cd8 t cells elevated antibody responses ebv found synergize ms associated mhc class il molecule hladrb11501 increase ms risk sevento fifteenfold respectively 1 moreover ebv infection seems precede ms onset several years nearly patients thus ebv infection currently appears prerequisite ms development increases risk autoimmune disease genetically susceptible individuals,1.0
headache migraine clinical practice guidelines systematic review assessment complementary alternative medicine recommendations background globally 3 billion people suffer either migraine tensiontype headache disorder lifetime approximately 50 american adults suffering headache migraine used complementary alternative medicine cam however quality quantity recommendations associated therapies across clinical practice guidelines cpgs treatment management conditions unknown purpose study identify quantity assess quality cam recommendationsmethodsmedline embase cinahl systematically searched 2009 april 2020 guidelines international network national center complementary integrative health websites also searched eligible cpgs cpgs included provided therapy recommendations eligible cpgs included written adult patients headache migraine cpgs containing cam recommendations assessed twice quality using agree ii instrument overall cpg cam sectionsresultsof 486 unique search results 21 cpgs eligible quality assessed fifteen cpgs mentioned cam 13 cpgs made cam recommendations overall cpg assessment yielded higher scaled domain percentages cam section across domains results highest lowest follows overall cam clarity presentation 667 vs 500 scope purpose 639 vs 611 stakeholder involvement 222 vs 139 rigour development 135 vs 94 applicability 63 vs 00 editorial independence 00 vs 00 conclusionsof eligible cpgs cam sections lower quality compared overall recommendations across domains agree ii instrument cpgs scored well serve framework discussion patients healthcare professionals regarding use cam therapies context headache migraine,0.0
restless legs syndrome people multiple sclerosis updated systematic review metaanalyses abstractbackgroundrestless legs syndrome rls sensorymotor disorder characterized uncomfortable sensation felt lower extremity aim systematic review metaanalyses provide updated information prevalence clinical characteristics rls amongst people multiple sclerosis pwms ii clarify rlsrelated factors pwmsmethodsmedline pubmed scopus embase searched inception april 2021 following keywords restless legs syndromenull rlsnull multiple sclerosisnull msnull analysis rls prevalence calculated percentage rls sufferers amongst pwms people without ms prevalence rls pooled separately pwms healthy controls regardless heterogeneity studies odds ratios ors 95 cis extracted data order analyze association ms rlsresultsnineteen studies included review 9 casecontrolled 10 crosssectional mean prevalence rls ms population 275 ranging 132 651 higher healthy controls based case control studies pooled rls prevalence much higher pwms healthy controls 4535 95 ci 30436759 p0001 majority studies found significant relationship presence rls pwms disability disease duration type ms age genderconclusionsour updated systematic review strengthens evidence increased risk rls amongst pwms nevertheless significant data reporting characteristics ms disease increases risk suffering rls still lacking,0.0
rat model widespread cerebral cortical demyelination induced intracerebral injection proinflammatory cytokines j vis exp 2021 sep 21 175 doi 103791 57879abstractmultiple sclerosis ms common immunemediated disease central nervous system cns progressively leads physical disability death caused white matter lesions spinal cord cerebellum well demyelination grey matter whilst conventional models experimental allergic encephalomyelitis suitable investigation cellmediated inflammation spinal cerebellar white matter fail address grey matter pathologies present experimental protocol novel rat model cortical demyelination allowing investigation pathological molecular mechanisms leading cortical lesions demyelination induced immunization lowdose myelin oligodendrocyte glycoprotein mog incomplete freunds adjuvant followed cathetermediated intracerebral delivery proinflammatory cytokines catheter moreover enables multiple rounds demyelination without causing injectioninduced trauma well intracerebral delivery potential therapeutic drugs undergoing preclinical investigation method also ethically favorable animal pain distress disability controlled relatively minimal expected timeframe implementation entire protocol around 8 10 weekspmid34633360 doi103791 57879,1.0
multiple sclerosis sri lanka epidemiology demographic patterns current trends summarycases multiple sclerosis increasingly recognized sri lanka south asia challenging concept ms disease west study estimates crude prevalence 778 cases per 100 000 population sri lanka carry secure diagnosis satisfying 2017 mcdonalds criteria seronegativity aqp4 mog antibodies demography clinical presentations similar western regional nations show excellent visual mobility outcomes long period follow studies necessary evaluate possible genetic predisposition contributing benign disease course,0.0
il1 hmgb1 antineurogenic endogenous neural stem cells sclerotic epileptic human hippocampus background dentate gyrus exhibits lifelong neurogenesis granulecell neurons supporting hippocampal dependent learning memory temporal lobe epilepsy patients animal models frequently hippocampaldependent learning memory difficulties show evidence reduced neurogenesis animal human temporal lobe epilepsy studies also shown strong innate immune system activation animal models reduces hippocampal neurogenesis sought determine neuroinflammation signals reduced neurogenesis epileptic human hippocampus potential reversibilitymethodswe isolated endogenous neural stem cells surgically resected hippocampal tissue 15 patients unilateral hippocampal sclerosis examined resultant neurogenesis growing either neurospheres ideal environment 3d cultures preserved inflammatory microenvironment 2d cultures mimicked itresults3d human hippocampal cultures largely replicated cellular composition inflammatory environment epileptic hippocampus microenvironment sclerotic human epileptic hippocampal tissue strongly antineurogenic sustained release proinflammatory proteins hmgb1 il1 il1 hmgb1 significantly reduce human hippocampal neurogenesis blockade il1r tlr 2 4 receptors il1ra boxa respectively significantly restores neurogenesis 2d 3d cultureconclusionour results demonstrate hmgb1 il1mediated environmental antineurogenic effect human tle identifying il1r tlr 2 4 receptors potential drug targets restoring human hippocampal neurogenesis temporal lobe epilepsy,0.0
plasma circulating vitamin c levels risk multiple sclerosis twosample mendelian randomization analysis abstractwhether vitamin c vitc supplementation can decrease multiple sclerosis ms risk remains controversial using data largescale genomewide association studies conducted twosample mendelian randomization mr analysis evaluate causal relationship plasma circulating vitc levels ms comprehensively mr analysis support causality genetically determined per 1 standard deviation increase around 20 mmol l circulating vitc levels ms risk 088 95ci 065118 p03822 supported complementary sensitivity analyses including weighted median mregger mr pleiotropy residual sum outlier test methods,0.0
gutbrain axis multiple sclerosis dysfunction pathological trigger consequence disease front immunol 2021 sep 21 12718220 doi 103389 fimmu2021718220 ecollection 2021abstracta large expending body evidence indicates gutbrain axis likely plays crucial role neurological diseases including multiple sclerosis ms whole gutbrain axis can considered bidirectional multicrosstalk pathway governs interaction gut microbiota organism perturbation commensal microbial population referred dysbiosis frequently associated increased intestinal permeability leaky gut allows entrance exogeneous molecules particular bacterial products metabolites can disrupt tissue homeostasis induce inflammation promoting local systemic immune responses altered gut microbiota therefore significant repercussions immune responses gut also distal effector immune sites cns indeed dysregulation bidirectional communication consequence dysbiosis implicated playing possible role pathogenesis neurological diseases multiple sclerosis ms gutbrain axis increasingly considered playing crucial role pathogenesis major focus specific gut microbiota alterations associated disease ms purported murine model experimental autoimmune encephalomyelitis eae gastrointestinal symptoms altered gut microbiota reported together increased intestinal permeability eae ms specific components microbiota shown modulate effector regulatory tcell responses therefore disease progression eae experiments germfree specific pathogenfree mice transferred microbiota associated disease clearly demonstrated possible role microbiota disease pathogenesis progression review evidence can point two possible consequences gutbrain axis dysfunction ms eae 1 proinflammatory intestinal environment leaky gut induced dysbiosis lead altered communication cns cholinergic afferent fibers thereby contributing cns inflammation disease pathogenesis 2 neuroinflammation affecting efferent cholinergic transmission result intestinal inflammation disease progressespmid34621267 pmcpmc8490747 doi103389 fimmu2021718220,0.0
rapid morphologic changes microglial cells upregulation mixed microglial activation state markers induced p2x7 receptor stimulation increased intraocular pressure background identification endogenous signals lead microglial activation key step understanding neuroinflammatory cascades atp release accompanies mechanical strain neural tissue p2x7 receptor atp expressed microglial cells examined morphological molecular consequences p2x7 receptor stimulation vivo vitro investigated contribution p2x7 receptor model increased intraocular pressure iop methodsin vivo experiments involved intravitreal injections transient sustained elevation iop vitro experiments performed isolated mouse retinal brain microglial cells morphological changes quantified vivo using sholl analysis expression mrna m1 m2like genes determined qpcr luciferin luciferase assay quantified retinal atp release fura2 indicated cytoplasmic calcium microglial migration monitored boyden chamberresultssholl analysis iba1stained cells showed retraction microglial ramifications 1 day injection p2x7 receptor agonist bzatp mouse retinae mean branch length ramifications also decreased cell body size expression nos2 tnfa arg1 chil3 mrna increased bzatp induced similar morphological changes ex vivo tissue isolated cx3cr1+ gfp mice suggesting recruitment external cells unnecessary immunohistochemistry suggested primary microglial cultures expressed p2x7 receptor functional expression demonstrated ca2+ elevation bzatp block specific antagonist a839977 bzatp induced process retraction cell body enlargement within minutes isolated microglial cells increased nos2 arg1 atp increased microglial migration required p2y12 receptor p2x7 receptor transient elevation iop led microglial process retraction cell body enlargement gene upregulation paralleling changes observed bzatp injection addition retinal atp release pressuredependent changes reduced p2x7 mice death retinal ganglion cells accompanied increased iop c57bl 6j p2x7 mice neuronal loss showed association microglial activationconclusionsp2x7 receptor stimulation induced rapid morphological activation microglial cells including process retraction cell body enlargement upregulation markers linked m1 m2type activation parallel responses accompanied iop elevation suggesting atp release p2x7 receptor stimulation influence early microglial response increased pressure,0.0
prevalence multiple sclerosis key cities brazil study passo fundo southern brazil abstract background improve comparability multiple sclerosis ms prevalence across brazilian regions brazilian committee treatment research ms implemented standardized approach assess prevalence disease five key cities deemed representative regions terms sociogeographical features inperson revision case feasible objective report pointprevalence ms passo fundo one key cities southern brazil methods sought identify ms patients living passo fundo july 1st 2015 primary source case ascertainment records offices neurologists neurosurgeons practicing city multiple secondary sources used maximize identification cases patients underwent inperson review diagnosis panel neurologists experience ms results identified 52 ms patients living passo fundo july 1st 2015 pointprevalence rate ms 264 100 000 population 95 confidence interval 197 346 100 000 among ms cases 42 808 female sex ratio 421 fortysix cases 885 categorized relapsingremitting ms remaining 6 cases secondary progressive ms 115 epidemiological clinical features comparable national international ms populations conclusions prevalence ms passo fundo one highest reported brazil far studies key brazilian cities using methodology currently carried,0.0
analysis sitespecific glycan profiles serum proteins patients multiple sclerosis neuromyelitis optica spectrum disorder pilot study glycobiology 2021 jun 14cwab053 doi 101093 glycob cwab053 online ahead printabstractglycosylation important biological functions proteins greatly affected diseases exploring glycosylation profile proteinspecific glycosylation sitespecific glycosylation may help understand disease etiology differentiate diseases ultimately develop therapeutics patients multiple sclerosis ms patients neuromyelitis optica spectrum disorder nmosd sometimes difficult differentiate due similarity clinical symptoms diseaserelated glycosylation profiles ms nmosd yet well studied analyzed sitespecific glycan profiles serum proteins patients using recently developed mass spectrometry technique total 286 glycopeptides 49 serum glycoproteins quantified compared healthy controls n 6 remitting ms n 45 remitting nmosd n 23 patients significant differences levels sitespecific nglycans inflammationassociated components igm igg1 igg2 complement components 8b co8b attractin central nerve systemdamagerelated serum proteins apolipoprotein d apod alpha1antitrypsin plasma kallikrein adamtslike protein 3 observed among three study groups furthered demonstrated sitespecific nglycans apod site 98 co8b sites 243 553 potential markers differentiate ms nmosd area receiver operating curve value greater 075 observations indicate remitting ms nmosd patients possess unique diseaseassociated glycosignature serum proteins conclude monitoring ones serum protein glycan profile using highthroughput analysis may provide additional diagnostic criterion differentiating diseases monitoring disease status estimating responsetotreatment effectpmid34132764 doi101093 glycob cwab053,0.0
exploring determinants community pharmacistled influenza vaccination middle eastern country national webbased crosssectional study background utilizing community pharmacists cps immunizers adopted various countries approach boost influenza vaccination coverage study aims explore lebanese cps willingness administer influenza vaccine identify factors associated willingnessmethodsthis webbased crosssectional study conducted 2 months 1st november end december 2020 selfreported data collected electronically lebanese cps anonymous questionnaire using google form collected data analyzed using statistical software spss statistical package social sciences bivariate multivariable analyses performed examine factors associated willingness cps administer influenza vaccineresultsa total 412 cps participated survey 769 willing administer influenza vaccines 90 good overall knowledge score 888 cps showed positive overall attitude score particularly towards involvement cps influenza vaccine provision willingness administer vaccine positively associated younger age aor 312 95 ci 15974040 higher education level aor 202 95 ci 10933741 previous experience immunization aor 272 95 ci 13205627 urbanicity pharmacy aor 1542 95 ci 12194627 extensive working hours aor 234 95 ci 11314845 working pharmacies operating roundtheclock showing positive attitude towards immunization aor 301 95 ci 18726422 towards provision influenza vaccines aor 1372 95 ci 1372138507 also positively associated willingness conversely patient privacy aor 055 95 ci 00790983 time cost professional development aor 055 95 ci 01720918 limited patients trust aor 039 95 ci 02030784 financial remuneration aor 018 95 ci 00880377 requirement formal certification vaccine administration aor 007 95 ci 00200279 negatively associated willingnessconclusionaddressing unearthed concerns related utilizing cps influenza immunizers concerted effort key success future implementation vaccination services pharmacies,0.0
influence igfi serum concentration muscular regeneration capacity patients sarcopenia background previous research described neuroprotective effect igfi supporting neuronal survival axon growth proliferation muscle cells therefore association igfi concentration muscle histology electrophysiological markers cohort patients sarcopenia dares investigationmethodsmeasurement serum concentrations igfi binding partners electromyographic measurements munix motor unit number index method muscle biopsies performed 31 patients acute hip fracture older age 60 years molecular markers denervation neural cell adhesion molecule ncam proliferation markers ki67 assessed immunofluorescence staining muscle biopsy tissue skeletal muscle mass bioelectrical impedance analysis handgrip strength measured assess sarcopenia status according ewgsop2 criteriaresultsthirtyone patients 20 women mean age 806 74 years included concentrations igfi binding partners significantly associated sarcopenia 0360 p 0047 munix 0512 p 0005 expression ncam 0380 p 0039 ki67 0424 p 0022 showed significant associations igfi concentrationsconclusionsthe findings suggest pathogenetic role igfi sarcopenia based muscle denervation,1.0
multidimensional approach sleep health multiple sclerosis abstractbackgroundalthough sleep disturbances common among people multiple sclerosis pwms understanding impact stymied limitations approaches sleep measurement within population aim study comprehensively phenotype sleep patterns pwms application emerging sevendomain framework includes sleep duration continuity timing quality rhythmicity regularity sleepinessmethodssleep domains estimated wristworn accelerometry epworth sleepiness scale pittsburgh sleep quality index responses extreme sleep values within domain constructed using previously published guidelines composite score extreme values calculated participant associations sleep domains severity ms symptoms explored pain fatigue depressive symptoms cognitive dysfunction resultsamong n49 participants median total sleep time 4563min median time spent awake sleep onset 37min sleepiness abnormal sleep timing poor sleep quality affected 33 35 45 participants respectively seventysix percent 2 sleep domains extreme ranges pwms longer sleep duration decreased sleep regularity compared nonms historical cohort older men greater daytime sleepiness poorer sleep quality higher composite sleep health score associated depressive symptoms lower sleep rhythmicity associated higher fatigue associations observed measures cognitive function sleep fragmentation duration quality rhythmicity composite scoreconclusionapplication sevendomain sleep health framework captures dynamic multifaceted aspects sleep feasible pwms offers potential improved understanding scope impact sleep disturbances pwms,0.0
methylphenidate may improve mental fatigue individuals multiple sclerosis pilot clinical trial backgroundfatigue common symptom multiple sclerosis ms previously attributed dopamine imbalance evidence suggests methylphenidate psychostimulant increases striatal prefrontal dopamine levels effective reducing fatigue various disorders however effect state vs trait mental fatigue ms yet examinedmethodsthis pilot study investigates efficacy methylphenidate decreasing selfreported mental fatigue 12 individuals ms doubleblind placebocontrolled crossover randomized clinical trialresultsour results show state trait msrelated fatigue reduced 4 weeks methylphenidate administration compared placebo,1.0
prospective study evaluate efficacy safety tolerability dietary supplement curcumin bcm95 subjects active relapsing multiple sclerosis treated subcutaneous interferon beta 1a 44 mcg tiw contain randomized controlled trial abstractbackgroundmultiple sclerosis ms complex disease sustained several pathogenic mechanisms combination therapy strategies targeting range disease mechanisms might represent ideal therapeutic approach investigated efficacy curcumin naturally occurring polyphenolic phytochemical potent antiinflammatory antioxidant properties subjects treatment ifn 1a test effects combination therapy clinical mri parameters inflammation neurodegeneration relapsing ms rms methodseighty active rms prospectively enrolled randomized 11 either ifncurcumin ifnplacebo group followed longitudinally clinical mri assessments 24 months primary endpoint efficacy curcumin versus placebo addon therapy new enlarging t2 lesions rms subjects treatment subcutaneous ifn 1a 44 mcg tiw efficacy clinical parameters relapses disability progression mri parameters inflammation t1 gdenhancing lesions combined unique activecua lesions neurodegeneration t1hypointense lesions grey matter loss white matter microstructural damage well safety tolerability curcumin explored secondary endpointsresultsten subjects dropped study month 12 6 ifncurcumin group 4 ifnplacebo group 27 month 24 11 ifncurcumin group 16 ifnplacebo group although betweengroup difference present terms proportion subjects free new enlarging t2 lesions lower proportion patients cua lesions noted month 12 ifncurcumin group comparison ifnplacebo group 75 vs 175 test p00167 result confirmed month 24 statistical analysis failed reveal difference two treatment groups ifncurcumin ifnplacebo terms relapses disability progression mri metrics inflammation mri changes suggestive ongoing neurodegeneration difference rate nature adverse events observed two treatment groupsconclusionalthough study dropout rate high allow definite conclusions findings suggest curcumin might add ifn 1a efficacy radiological signs inflammation ms seem exert neuroprotective effect assessed clinical mri parameters nct01514370,1.0
impact multiple sclerosis diseasemodifying therapies sarscov2 vaccineinduced antibody t cell immunity medrxiv 2021 sep 202021091021262933 doi 101101 2021091021262933 preprintabstractvaccineelicited adaptive immunity essential prerequisite effective prevention control coronavirus 19 covid19 treatment multiple sclerosis ms involves diverse array diseasemodifying therapies dmts target antibody cellmediated immunity yet comprehensive understanding ms dmts impact sarscov2 vaccine responses lacking completed detailed analysis sarscov2 vaccineelicited spike antigenspecific igg t cell responses cohort healthy controls ms participants six different treatment categories two specific dmt types sphingosine1phosphate s1p receptor modulators anticd20 monoclonal antibodies mab resulted significantly reduced spikespecific igg responses longer duration anticd20 mab treatment prior sarscov2 vaccination associated absent antibody responses except reduced cd4+ t cell responses s1ptreated patients spikespecific cd4+ cd8+ t cell reactivity remained robust across ms treatment types findings important implications clinical practice guidelines vaccination recommendations ms patients immunosuppressed populationspmid34580672 pmcpmc8475959 doi101101 2021091021262933,0.0
regional brain atrophy related social cognition impairment multiple sclerosis abstract background multiple sclerosis exhibits specific neuropathological phenomena driving global regional brain atrophy clinical level disease related functional decline cognitive domains working memory processing speed verbal fluency however compromise socialcognitive abilities concentrated interest recent years despite available evidence suggesting risk disorganization social life recent studies used minisea test assess compromise social cognition found relevant relationships memory executive functions well level global regional brain atrophy objective present article aimed identify structural changes related sociocognitive performance sample patients relapsingremitting multiple sclerosis methods 68 relapsingremitting multiple sclerosis chilean patients 50 healthy control subjects underwent mri scans neuropsychological evaluation including socialcognition tasks total brain white matter gray matter volumes estimated also voxelbased morphometry applied evaluate regional structural changes results patients exhibited lower scores neuropsychological tests social cognition exhibited significant decrease group mostly related declining social perception normalized brain volume white matter volume significantly decreased compared healthy subjects regional brain atrophy analysis showed changes insular cortex medial frontal cortices significantly related variability socialcognitive performance among patients conclusions present study social cognition correlated deterioration verbal fluency despite fact previous studies reported link memory executive functions identification specific structural correlates supports comprehension phenomenon independent source cognitive disability patients,0.0
role hydrazinerelated chemicals cancer neurodegenerative disease chem res toxicol 2021 aug 11 doi 101021 acschemrestox1c00150 online ahead printabstracthydrazinerelated chemicals hrcs carcinogenic neurotoxic potential found certain mushrooms plants used food products employed various industries including aerospace propensity induce dna damage mostly o6 n7 8oxoguanine lesions resulting multiple downstream effects linked cancer neurological disease cycling cells unrepaired dna damage leads mutation uncontrolled mitosis contrast postmitotic neurons attempt reenter cell cycle undergo apoptosis nonapoptotic cell death biomarkers exposure hrcs can used explore whether substances risk factors sporadic amyotrophic laterals sclerosis noninherited neurodegenerative diseases focus paperpmid34379394 doi101021 acschemrestox1c00150,0.0
splicevariant specific effects cacna1h mutation associated writers cramp abstractthe cacna1h gene encodes 1 subunit low voltageactivated cav32 ttype calcium channel important regulator neuronal excitability alternative mrna splicing can generate multiple channel variants distinct biophysical properties expression patterns two major splice variants containing lacking exon 26 26 found different human tissues study report splice variant specific effects cav32 mutation found patients autosomal dominant writers cramp specific type focal dystonia previously reported r481c missense mutation caused gain function effect expressed cav32 + 26 accelerating recovery inactivation show mutation expressed short variant channel 26 observe significant increase current density compared wildtype cav32 26 effect recovery inactivation lost data add growing evidence functional expression calcium channel mutations depends splice variant examined,0.0
wernicke#39 s encephalopathy mimicking multiple sclerosis young female patient postbariatric gastric sleeve surgery j community hosp intern med perspect 2021 sep 20 11 5 658661 doi 101080 2000966620211949792 ecollection 2021abstractwe describe case wernickes encephalopathy secondary thiamine b1 deficiency patient status postbariatric sleeve gastrectomy presenting symptoms newonset weakness diplopia confusion young female patient raised suspicion multiple sclerosis ms given history bariatric surgery thiamine levels checked revealing significant vitamin b1 thiamine deficiency case highlights importance thorough history taking misdiagnosis ms case resulted irreversible neurological deterioration hematological infectious consequences associated inappropriate administration diseasemodifying therapies also important note severe vitamin deficiency occurred despite medication compliancepmid34567458 pmcpmc8462913 doi101080 2000966620211949792,0.0
effectiveness statins potential therapy multiple sclerosis systematic review randomized controlled trials cureus 2021 sep 19 13 9 e18092 doi 107759 cureus18092 ecollection 2021 sepabstractevidence effectiveness statins lipidlowering agents retarding progression multiple sclerosis ms disabling neurological disease autoimmune etiology highlighted animal studies observational studies proposed immunemodulatory actions neuroprotective effects statins make promising treatment option ms needs explored systematic review aim investigate role different statins monotherapy combination established ms medications improving clinical radiological course ms variants including optic neuritis using randomized controlled trials rcts systematically searched pubmed pubmed central pmc medline cochrane library scopus databases using regular keywords medical subject headings terms randomized controlled trials statin used variants ms including studies statins used optic neuritis published april 2021 included review data effects relapse rate expanded disability status scale edss alterations changes magnetic resonance imaging mri lesions collected included studies seven studies total 831 patients average duration followup six 36 months included review five trials statins addon interferon therapy relapsingremitting multiple sclerosis rrms four studies assessed good quality remaining study featured high risk bias one trial simvastatin monotherapy secondary progressive multiple sclerosis spms included assessed good methodological quality low risk bias adequate patient number trial simvastatin monotherapy patients optic neuritis included evaluated good quality study still low number participants short duration followup used changes disease relapse rate edss primary outcome variables mri lesions changes secondary outcome variable studies rrms showed significant effects primary secondary outcomes study spms featured significant improvement edss simvastatintreated patients effect relapse rate mri changes simvastatin use optic neuritis enhances clinical visual outcomes significant effect mri changes rate progression definite ms contrast animal studies observational studies randomized controlled trials replicate positive effects statins used monotherapy combined interferon beta patients rrms optic neuritis relapse rate edss mri changes however trials statins spms showed promising effect disability progression edss score might support proposed immunemodulatory neuroprotective role statins serve baseline rcts applying statins monotherapy combination established ms therapiespmid34692306 pmcpmc8525664 doi107759 cureus18092,1.0
potential markers sample size estimations hereditary spastic paraplegia type 5 background aim identify potential biomarkers assess therapeutic efficacy hereditary spastic paraplegias type 5 spg5 investigating clinical cerebrospinal fluid csf magnetic resonance imaging mri featuresmethodswe performed crosssectional study compare spg5 patients age sexmatched healthy controls underwent conventional quantitative mri techniques spinal cord c1t9 brain spg5 patients also underwent assessment clinical status csf biomarkers 27hydroxycholesterol neurofilament light identified set markers standardized effect sizes t 05 estimate sample sizes disease progression disease duration 14 years vs 14 years resultsseventeen genetically confirmed spg5 patients 11 men 6 women age range 1349 years median disease duration 14 years enrolled compared healthy controls total spinal cord area sca spg5 patients reduced particularly thoracic levels cervical levels 1227 thoracic levels 4160 patients show significant alterations brain signal abnormalities atrophy relative controls total 10 surrogate markers selected minimum sample size achieved measurement sca t9 n 22 much less required using clinical disability assessment n 124 conclusionsspg5 patients showed distinct mri features spinal cord atrophy without significant brain alterations finding supports measurements spinal cord t9 level potential endpoint spg5 clinical trialstrial registration clinicaltrialsgov nct04006418 registered 05 july 2019 https clinicaltrialsgov ct2 show nct04006418termnct04006418draw2rank1,0.0
incidence acute myocardial infarction elective spinal fusions joint replacement surgery united states largescale retrospective observational cohort study 322 585 patients background acute myocardial infarction ami uncommon fatal complication among patients undergoing elective spinal fusion surgery sf total hip arthroplasty tha total knee arthroplasty tka objective estimate incidence ami among adults undergoing elective sf tha tka different postoperative risk windows characterize highrisk subpopulations united statesmethodsa retrospective cohort study conducted using data longitudinal electronic healthcare record ehr database january 1 2007 june 30 2018 icd codes used identify sf tha tka ami selected clinical characteristics incidence proportions ips 95 confidence intervals estimated following risk windows index hospitalization 30 90 180 365 days postoperationresultsa total 67 533 sf patients 87 572 tha patients 167 480 tka patients eligible study ip ami sf tha tka ranged 036 028 025 index hospitalization 105 093 085 365 days postoperation respectively ip ami higher among patients older male longer hospital stays history ami history diabetesconclusionthe ip postoperative ami generally highest among sf cohort compared tha tka cohorts additionally potential highrisk populations identified future studies area warranted confirm findings via improved confounder control identify effect measure modifiers,0.0
minimally invasive transforaminal lumbar interbody fusion versus oblique lateral interbody fusion lumbar degenerative disease metaanalysis background minimally invasive transforaminal lumbar interbody fusion mistlif oblique lateral interbody fusion olif widely used treatment lumbar degenerative diseases present study metaanalysis conducted compare clinical radiographic efficacy two proceduresmethodsa systematic literature review performed quality retrieved studies evaluated newcastleottawa scale nos clinical outcomes including operation time intraoperative blood loss improvement visual analogue scale vas improvement oswestry disability index odi japanese orthopaedic association back pain evaluation questionnaire joabpeq effectiveness rate complications addition radiographic outcomes including restoration disc height disc angle overall lumbar lordosis fusion rate subsidence extracted input fixed random effect model compare efficacy mistlif olifresultsseven qualified studies included clinically olif resulted less intraoperative blood loss shorter operation time mistlif improvement vas leg pain obvious olif group p 00001 whereas improvement vas back pain p 008 odi p 098 well joabpeq effectiveness rate p 018 similar two groups radiographically olif effective restoring disc height p 001 equivalent improving disc angle p 018 lumbar lordosis p 048 compared mistlif fusion rate p 011 similar groups subsidence severe mistlif group p 000001 conclusionsthe evidence suggests olif associated shorter operation time supplementary fixation prone position less intraoperative blood loss mistlif can lead better leg pain alleviation disc height restoration subsidence resistance differences regarding back pain relief functional recovery complications disc angle restoration lumbar lordosis restoration fusion rate found however due limited number studies results confirmed highlevel studies fully compare therapeutic efficacy mistlif oliftrial registrationprospero id crd42020201903,0.0
identifying discriminative features diagnosis kashinbeck disease among adolescents abstractintroductiondiagnosing kashinbeck disease kbd involves damages multiple joints carries variable clinical symptoms posing great challenge diagnosis kbd clinical practitioners however still unclear clinical features kbd informative diagnosis kashinbeck disease among adolescentmethodswe first manually extracted 26 possible features including clinical manifestations pathological changes xray images 400 kbd 400 nonkbd adolescents features performed four classification methods ie random forest algorithms rfa artificial neural networks anns support vector machines svms linear regression lr four feature selection methods ie rfa minimum redundancy maximum relevance mrmr support vector machine recursive feature elimination svmrfe relief performance diagnosis kbd respect different classification models evaluated sensitivity specificity accuracy area receiver operating characteristic roc curve auc resultsour results demonstrated 10 26 discriminative features displayed powerful performance regardless chosen classification models feature selection methods ten discriminative features distal end phalanges alterations metaphysis alterations carpals alterations clinical manifestations ankle joint movement limitation enlarged finger joints flexion distal part fingers elbow joint movement limitation squatting limitation deformed finger joints wrist joint movement limitationconclusionsthe selected ten discriminative features provide fast effective diagnostic standard kbd adolescents,0.0
elevated levels serum cd5 antigenlike protein distinguish secondary progressive multiple sclerosis disease subtypes abstractcd5 antigenlike cd5l protein macrophagesecreted protein roles immunomodulation lipid homeostasis compared serum cd5l levels healthy controls individuals diagnosed clinically isolated syndrome relapsing remitting rr secondary progressive sp primary progressive pp multiple sclerosis ms cd5l increased spms relative controls rrms ppms spms cd5l associated longer disease duration independent age sex disease severity positive relationship cd5l disease duration spms suggests chronic peripheral inflammatory profile compared subtypes particularly ppms warranting investigation functional roles cd5l ms,0.0
comparing fall detection methods people multiple sclerosis prospective observational cohort study abstractbackground falls occur across population common negative sequelae people multiple sclerosis ms given prevalence impact falls accurate measures fall frequency needed study compares sensitivity false discovery rates three methods fall detection current gold standard prospective paper fall calendars realtime selfreporting automated detection latter two novel bodyworn devicemethods falls twentyfive people ms recorded eight weeks prospective fall calendars realtime bodyworn selfreport automated bodyworn detector concurrently eligible individuals adults ms enrolled randomized controlled trial fall prevention intervention entry criteria least two falls nearfalls previous two months expanded disability status scale 60 community dwelling ms relapse previous month sensitivity proportion true falls detected false discovery rates proportion false reports generated fall detection methods compared true fall fall reported least two methods false report fall reported one method trial registered clinicaltrialsgov nct02583386 closedresults 1 276 persondays fall counting three methods use simultaneously 1344 unique fall events 85 114 true falls 915 1230 false reports fall calendars lowest sensitivity 0614 lowest false discovery rate 0067 automated detector highest sensitivity 0921 highest false discovery rate 0919 methods generated one false report per day fall detectionrelated adverse eventsconclusion fall calendars likely underestimate fall frequency around 40 automated detector evaluated misses falls likely overestimates number falls around one fall per day additional research needed produce ideal fall detection counting method use clinical research applicationsfunding united states department veterans affairs rehabilitations research development service,0.0
signal inhibitory receptor leukocytes1 recognizes bacterial endogenous amphipathic helical peptides abstractsignal inhibitory receptor leukocytes1 sirl1 negative regulator myeloid cell function dampens antimicrobial responses show different species genus staphylococcus secrete sirl1engaging factors screening library singlegene transposon mutants staphylococcusaureus identified factors phenolsoluble modulins psms psms amphipathic helical peptides involved multiple aspects staphylococcal virulence physiology cytotoxic activate chemotactic formyl peptide receptor2 fpr2 immune cells human cathelicidin ll37 also amphipathic helical peptide antimicrobial chemotactic activities structurally functionally similar type psms demonstrate type psms multiple staphylococcal species well human cathelicidin ll37 activate sirl1 suggesting sirl1 recognizes helical peptides amphipathic arrangement hydrophobicity although able show direct binding sirl1 upon rational peptide design identified artificial peptides capacity ligate sirl1 segregated cytotoxic fpr2activating properties allowing specific engagement sirl1 conclusion propose staphylococcal psms human ll37 potential new class natural ligands sirl1,0.0
characterization agerelated differences human choroid plexus volume microstructural integrity blood perfusion using multiparameter magnetic resonance imaging front aging neurosci 2021 sep 17 13734992 doi 103389 fnagi2021734992 ecollection 2021abstractthe choroid plexus cp important cerebral structure involved cerebrospinal fluid production transport solutes brain recent studies uncovered involvement cp neurological disorders alzheimers disease multiple sclerosis however understanding human agerelated microstructural functional changes cp aging neuropathology limited crosssectional study investigated age sex differences cp structure function using advanced quantitative magnetic resonance imaging methodology large cohort n 155 cognitively unimpaired individuals wide age range 21 94 years analysis included volumetric measurements relaxometry measures t 1 t 2 diffusion tensor imaging dti measures fractional anisotropy fa mean diffusivity md well measures cerebral blood flow cbf results revealed cp volume increasing advancing age conjecture novel observation likely attributed alterations cp microstructure function well ventriculomegaly indeed also found cbf lower advanced age consistent previous studies t 1 t 2 md higher fa lower advanced age attribute functional microstructural differences deteriorated cp structural integrity aging furthermore relaxometry dti measures found associated differences blood perfusion revealing lower microstructural integrity lower cbf finally agreement literature sexrelated differences md cbf statistically significant work lays foundation ongoing investigation involvement cp neurodegenerationpmid34603011 pmcpmc8485051 doi103389 fnagi2021734992,0.0
novel roles tim family immune regulation autoimmune diseases front immunol 2021 sep 17 12748787 doi 103389 fimmu2021748787 ecollection 2021abstractt cell ig mucin domain tim protein family members identified important regulators immune response name indicates tim proteins originally considered t cellspecific markers mainly regulate responses t helper cells however accumulating evidence indicates tims also expressed antigenpresenting cells apcs monocytes macrophages dendritic cells dcs b cells even plays various roles natural killer cells nks mast cells recent years expression function tims different cells identification new ligands tim family suggested tim family plays crucial role immune regulation addition relationship tim family gene polymorphisms susceptibility several autoimmune diseases expanded knowledge role tim proteins immune regulation review discuss tim family affects immunomodulatory function potential role tim family typical autoimmune diseases including multiple sclerosis ms rheumatoid arthritis ra systemic lupus erythematosus sle type 1 diabetes t1d deeper understanding immunoregulatory mechanism tim family might provide new insights clinical diagnosis treatment autoimmune diseasespmid34603337 pmcpmc8484753 doi103389 fimmu2021748787,0.0
brain muscle metabolic changes fdgpet stiff person syndrome spectrum disorders front neurol 2021 sep 17 12692240 doi 103389 fneur2021692240 ecollection 2021abstractobjective report clinical characteristics fluorodeoxyglucose positron emission tomography fdgpet findings brain muscles individuals stiff person syndrome sps spectrum disorders spssds methods retrospective cohort study 1997 2018 johns hopkins hospital identified 170 individuals sps cerebellar ataxia ca associated antiglutamic acid decarboxylase antigad 65 antibodies fiftyone underwent fdgpet 50 involving body 30 dedicated brain acquisition clinical immunological profiles extracted via medical record review brain scans analyzed quantitatively using neuroq software comparison averaged normal database body scans reviewed qualitatively blinded nuclear medicine radiologist results mean age symptom onset 415 years range 1275 years majority female 68 white 64 patients 82 sps majority classic phenotype 18 ca three paraneoplastic process fortyseven serum antigad two antiamphiphysin one antiglycine receptor antibodies brain metabolic abnormalities seen sps ca significant differences groups noted right superior frontal cortex right sensorimotor cortex left inferior parietal cortex bilateral thalami vermis left cerebellum patients 62 demonstrated muscle hypermetabolism commonly bilateral involving upper extremities axial muscles neither brain muscle metabolism correlated functional outcomes treatments conclusions metabolic changes seen fdgpet present brain muscle many individuals spssd future studies needed assess whether fdgpet can help aid diagnosis monitoring individuals spssdpmid34603180 pmcpmc8484315 doi103389 fneur2021692240,0.0
detection healthrelated events behaviours wearable sensor lifestyle data using symbolic intelligence proofofconcept application care multiple sclerosis sensors basel 2021 sep 17 21 18 6230 doi 103390 s21186230abstractin paper demonstrate potential knowledgedriven framework improve efficiency effectiveness care remote intelligent assessment specifically present rulebased approach detect health related problems wearable lifestyle sensor data add clinical value take informed decisions followup intervention use owl 2 ontologies underlying knowledge representation formalism modelling contextual information highlevel concepts relations among conceptual model framework defined top existing modelling standards sosa wadm promoting creation interoperable knowledge graphs top symbolic knowledge graphs define rulebased framework infusing expert knowledge form shacl constraints rules recognise patterns anomalies situations interest based predefined stored rules conditions dashboard visualizes sensor data detected events facilitate clinical supervision decision making preliminary results performance scalability presented focus group clinicians involved exploratory research study revealed preferences perspectives shape future clinical research using frameworkpmid34577437 doi103390 s21186230,0.0
association clinical phenotypes dermatomyositis polymyositis myositisspecific antibodies overlap systemic autoimmune diseases medicine baltimore 2021 sep 17 100 37 e27230 doi 101097 md0000000000027230abstractthe aim study evaluate association clinical phenotypes dermatomyositis dm polymyositis pm myositisspecific antibodies msas overlap diagnosis systemic autoimmune diseasesthis crosssectional study conducted 67 patients dm 27 patients pm recruited regional hospital southern taiwan clinical phenotypes dm pm assessed msas measured using commercial line blot assay association clinical phenotypes dm pm msas overlap diagnosis systemic autoimmune diseases performed using univariate multiple logistic regression analysesclinically patients dm pm overlap diagnosis systemic sclerosis associated higher risk interstitial lung diseases ilds odds ratio 673 p 048 raynaud phenomenon 730 p 034 malignancy 35077 p 013 risk malignancy also associated older age 131 p 012 male patients associated higher risk fever msas antiaminoacyltrna synthetase antibodies associated ild antinuclear antibody associated lower risk arthritis antitranscription intermediary factor 1gamma antibodies associated milder symptoms muscle weakness antiku antibodies associated overlap diagnosis systemic lupus erythematosus antiro52 antibodies associated development raynaud phenomenon sjgren syndromemsas overlap diagnosis systemic sclerosis significantly associated clinical phenotypes dm pm physicians vigilant malignancy older dm pm patients overlap diagnosis systeic sclerosis possibility developing ild patients overlap diagnosis systemic sclerosis serum positivity antiaminoacyltrna synthetase antibodies consideredpmid34664863 doi101097 md0000000000027230,0.0
acidsensing ion channels expression function resident infiltrating immune cells central nervous system front cell neurosci 2021 sep 17 15738043 doi 103389 fncel2021738043 ecollection 2021abstractperipheral central immune cells critical fighting disease can also play pivotal role onset progression variety neurological conditions affect central nervous system cns tissue acidosis often present cns pathologies multiple sclerosis epileptic seizures depression local ph also reduced periods ischemia following stroke traumatic brain injury spinal cord injury pathological increases extracellular acidity can activate class protongated channels known acidsensing ion channels asics asics primarily studied due ubiquitous expression throughout nervous system less well recognized also found various types immune cells review explore currently known expression asics peripheral cnsresident immune cells channel activation pathological tissue acidosis may lead altered immune cell function turn modulates inflammatory pathology cns identify gaps literature asics immune cell function characterized neurotrauma knowledge contribution asics immune cell function neuropathology will critical determining whether therapeutic benefits asic inhibition might due part effect immune cellspmid34602982 pmcpmc8484650 doi103389 fncel2021738043,0.0
role gut microbiota gutbrain interplay selected diseases central nervous system int j mol sci 2021 sep 17 22 18 10028 doi 103390 ijms221810028abstractthe gut microbiome attracted increasing attention researchers recent years microbiota can specific complex crosstalk host particularly central nervous system cns creating socalled gutbrain axis communication gut intestinal microbiota brain involves secretion various metabolites shortchain fatty acids scfas structural components bacteria signaling molecules moreover imbalance gut microbiota composition modulates immune system function tissue barriers bloodbrain barrier bbb therefore aim literature review describe gutbrain interplay may contribute development various neurological disorders combining fields gastroenterology neuroscience present recent findings concerning effect altered microbiota neurodegeneration neuroinflammation including alzheimers parkinsons diseases well multiple sclerosis moreover impact pathological shift microbiome selected neuropsychological disorders ie major depressive disorders mdd autism spectrum disorder asd also discussed future research effect balanced gut microbiota composition gutbrain axis help identify new potential opportunities therapeutic interventions presented diseasespmid34576191 doi103390 ijms221810028,0.0
fingolimod diabetic retinopathy drug repurposing study front pharmacol 2021 sep 17 12718902 doi 103389 fphar2021718902 ecollection 2021abstractthis study aimed investigate interactions fingolimod sphingosine 1phosphate receptor s1pr agonist melanocortin receptors 1 5 mcr1 mcr5 particular investigated effects fingolimod drug approved treat relapsingremitting multiple sclerosis retinal angiogenesis mouse model diabetic retinopathy dr showed molecular modeling approach fingolimod can bind goodpredicted affinity mc1r mc5r thereafter investigated fingolimod actions retinal mc1rs mc5rs c57bl 6j mice diabetes induced c57bl 6j mice streptozotocin injection diabetic control c57bl 6j mice received fingolimod oral route 12 weeks monthly intravitreally injection mc1r antagonist agrp mc5r antagonist pg20n selective s1pr1 antagonist ex 26 diabetic animals treated fingolimod showed decrease retinal vascular endothelial growth factor vegfa vascular endothelial growth factor receptors 1 2 vegfr1 vegfr2 compared diabetic control group fingolimod cotreatment mc1r mc5r selective antagonists significantly p 005 increased retinal vegfr1 vegfr2 vegfa levels compared mice treated fingolimod alone diabetic animals treated fingolimod plus ex 26 s1pr1 selective blocker vegfr1 vegfr2 vegfa levels diabetic mice group group diabetic mice treated fingolimod alone vascular protective effect fingolimod activation mc1r mc5r evidenced also fluorescein angiography mice finally molecular dynamic simulations showed strong similarity fingolimod mc1r agonist bms470539 conclusion antiangiogenic activity exerted fingolimod dr seems mediated s1p1r also melanocortin receptorspmid34603029 pmcpmc8484636 doi103389 fphar2021718902,0.0
pharmacological treatment epilepsy recent advances future perspectives abstractthe pharmacological armamentarium epilepsy expanded considerably last three decades currently includes 30 different antiseizure medications despite large armamentarium one third people epilepsy fail achieve sustained seizure freedom currently available medications sobering fact however mitigated evidence clinical outcomes many people epilepsy improved years particular physicians now unprecedented opportunities tailor treatment choices characteristics individual order maximize efficacy tolerability present article discusses advances drug treatment epilepsy last 5 years focusing particular comparative effectiveness trials secondgeneration drugs introduction new pharmaceutical formulations emergency use results achieved newest medications article also includes discussion potential future developments including derived advances information technology development novel precision treatments introduction disease modifying agents discovery biomarkers facilitate conduction clinical trials well routine clinical management,0.0
investigation blood leptin adropin levels patients multiple sclerosis consortclinical study medicine baltimore 2021 sep 17 100 37 e27247 doi 101097 md0000000000027247abstractbackground effects adipokines investigated multiple sclerosis ms literature results uncertain subgroups like adropin previously studied primarily aimed determine leptin adropin levels ms potential use biomarkermethods study experimental research 44 ms patients diagnosed according mcdonald criteria included patient group 40 people without ms diagnosis risk factors took part control group demographic data height weight body mass index blood glucose thyroidstimulating hormone alanine transaminase aspartate transaminase creatinine lowdensity lipoprotein leptin adropin levels presence hypertension diabetes mellitus coronary artery disease recorded expanded disability status scale disease duration also evaluated patient group data presented mean standard deviationsresults mean blood leptin value patient group 612 534 ng ml significantly lower value control group 1302 825 ng ml p 001 patient group mean adropin level 50412 31117 ng ml significantly lower control group 7470 30942 ng ml p 001 statistically insignificant differences found body mass index glucose alanine transaminase aspartate transaminase thyroidstimulating hormone lowdensity lipoprotein levels p 001 conclusion first study evaluated adropin levels patients ms relationship ms leptin levels still unclear therefore study might helpful elucidate ms pathogenesis provide supportive criteria diagnosispmid34664869 doi101097 md0000000000027247,0.0
preliminary study association cigarette smoking risk neuromyelitis optica spectrum disorder medicine baltimore 2021 sep 17 100 37 e27234 doi 101097 md0000000000027234abstractvarious studies revealed association cigarette smoking increased risk multiple sclerosis ms however role neuromyelitis optica spectrum disorder nmosd remains elusive therefore present casecontrol study aimed assess association active passive cigarette smoking risk ms nmosdthirtysix patients nmosd 46 patients ms 122 healthy individuals included study standardized questionnaires telephone interviews used collect information regarding active passive cigarette smoking behaviors patients normal controlsthe risk ms significantly higher among smokers among nonsmokers odds ratio 2166 95 confidence interval 11094170 p 027 analysis risk active passive smokers male smokers nonsmokers showed statistical difference however neither smokers active smokers greater lower risk nmosd nonsmoking counterpartsour preliminary study showed significant association cigarette smoking risk nmosd strongly suggesting unlike ms cigarette smoking might confer nmosd susceptibility least northern han chinese populationpmid34664866 doi101097 md0000000000027234,0.0
multiple sclerosis endogenous opioid system front neurosci 2021 sep 17 15741503 doi 103389 fnins2021741503 ecollection 2021abstractmultiple sclerosis ms autoimmune disease characterized chronic inflammation neuronal degeneration demyelinating lesions within central nervous system mechanisms underlie pathogenesis progression ms fully known current therapies limited efficacy preclinical investigations using murine experimental autoimmune encephalomyelitis eae model ms well clinical observations patients ms provide converging lines evidence implicating endogenous opioid system pathogenesis disease recent years become increasingly clear endogenous opioid peptides binding mor kor opioid receptors dor function immunomodulatory molecules within immune nervous systems endogenous opioid system also well known play role development chronic pain negative affect common comorbidities ms dysregulation opioid system may mechanism contributes pathogenesis ms associated symptoms review evidence connection endogenous opioid system ms explore mechanisms opioidergic signaling might contribute pathophysiology symptomatology mspmid34602975 pmcpmc8484329 doi103389 fnins2021741503,1.0
cancer diabetes interlinking metabolic pathways repurposing actions antidiabetic drugs abstractcancers regarded one main causes death result high health burden worldwide management cancer include chemotherapy surgery radiotherapy chemotherapy involves use chemical agents cytotoxic actions utilised single treatment combined treatment however managements cancer chemotherapy poses setbacks cytotoxicity normal cells problem anticancer drug resistance therefore use therapeutic agents antidiabetic drugs one alternative interventions used addressing limitations use anticancer agents antidiabetic drugs sulfonylureas biguanides thiazolidinediones showed beneficial repurposing actions management cancer thus activities drugs cancer attributed metabolic links two disorders includes hyperglycaemia hyperinsulinemia inflammation oxidative stress well obesity furthermore studies showed use antidiabetic drugs serve risk factors development cancerous cells particularly pancreatic cancer however beneficial role chemical agents overweighs detrimental actions cancer management hence present review indicates metabolic links cancer diabetes mechanistic actions antidiabetic drugs management cancers,0.0
proceedings international cancer imaging society meeting 20th annual teaching course n,0.0
assessing direct healthcare costs restricted selfreported data scoping review background absence electronic health records analysis direct healthcare costs often relies resource utilisation data collected patientreported surveys scoping review explored availability use methodological details selfreported healthcare service utilisation cost data assess healthcare costs irelandmethodspopulation health surveys identified irish data repositories details collated inventory inform literature search irish cost studies published peerreviewed grey sources 2009 2019 included used selfreported data healthcare utilisation cost two independent researchers extracted studies details prismascr guidelines used reportingresultsin total 27 surveys identified containing varying details healthcare utilisation cost health status demographic characteristics healthrelated risk behaviour surveys 21 general population surveys six studyspecific adhoc surveys furthermore 14 cost studies identified used retrospective selfreported data healthcare utilisation cost ten identified surveys nine cost studies used adhoc surveys five used data preexisting population surveys compared population surveys adhoc surveys contained detailed information resource use albeit smaller sample sizes recall periods ranged 1 week frequently used services 1 year rarer service use longer onceoff costs range perspectives societal healthcare public sector costing approaches bottomup costing mix topdown bottomup used majority studies n 11 determined unit prices using multiple sources including national healthcare tariffs literature expert views moreover studies n 13 reported limitations concerning data availability risk bias generalisability various sampling data collection analysis strategies employed minimise theseconclusionpopulation surveys can aid cost assessments jurisdictions lack electronic health records unique patient identifiers data interoperability increase utilisation researchers wanting conduct cost analyses need aware access existing data sources future population surveys designed address reported limitations capture comprehensive healthrelated demographic resource use data,0.0
hsf1 involved suppressing a1 phenotype conversion astrocytes following spinal cord injury rats background two activation states reactive astrocytes termed a1 a2 subtypes emerge lesion sites following spinal cord injury sci a1 astrocytes known neurotoxic participate neuropathogenesis whereas a2 astrocytes assigned neuroprotective activity heat shock transcription factor 1 hsf1 plays roles protecting cells stressinduced apoptosis controlling inflammatory activation unknown whether hsf1 involved suppressing conversion a1 astrocytes following scimethodsa contusion model rat spinal cord established correlations hsf1 expression onset a1 a2 astrocytes assayed western blot immunohistochemistry 17aag agonist hsf1 employed treat primary cultured astrocytes following challenge a1astrocyteconditioned medium acm containing 3 ng ml il1 30 ng ml tnf 400 ng ml c1q induction a1 subtype effects 17aag phenotype conversion astrocytes well underlying signal pathways examined western blot immunohistochemistryresultsthe protein levels hsf1 significantly increased 4 days 7 days following rat sci showing colocalization astrocytes meanwhile c3positive a1 astrocytes observed accumulate lesion sites peak 1 day 4 days distinctively s100a10positive a2 subtype reached peak 4 days 7 days incubation primary astrocytes acm markedly induced conversion a1 phenotype whereas addition 17aag significantly suppressed inducible effects without conversion a2 subtype activation hsf1 remarkably inhibited activities mapks nfb responsible regulation c3 expression administration 17aag lesion sites rats able reduce accumulation a1 astrocytesconclusioncollectively data reveal novel mechanism astrocyte phenotype conversion following sci hsf1 plays key roles suppressing excessive increase neurotoxic a1 astrocytes,1.0
tftenricher python toolbox annotation enrichment analysis transcription factor target genes background transcription factors tfs upstream regulators orchestrate gene expression therefore centrepiece bioinformatics studies core strategy understand biological context genes proteins includes annotation enrichment analysis gene ontology term enrichment methods well suited analysing groups tfs particularly true since methods aim include downstream processes given set tfs expected top ontologies revolve around transcription processesresultswe present tftenricher python toolbox focuses specifically identifying gene ontology terms cellular pathways diseases overrepresented among genes downstream userdefined sets human tfs evaluated inference downstream gene targets respect false positive annotations found inference based coexpression best predict downstream processes based downstream genes tftenricher uses common databases gene functionalities including go kegg reactome calculate functional enrichments applying tftenricher differential expression tfs 21 diseases found significant terms associated disease mechanism gene set enrichment analysis dataset predominantly identified processes related transcriptionconclusions availabilitythe tftenricher package enables users search biological context set tfs downstream genes tftenricher available python 3 toolbox https githubcom rasma774 tftenricher gnu gpl license minimal dependencies,1.0
possible role butyrylcholinesterase fat loss decreases inflammatory levels patients multiple sclerosis treatment epigallocatechin gallate coconut oil pilot study nutrients 2021 sep 16 13 9 3230 doi 103390 nu13093230abstract 1 background multiple sclerosis ms characterised loss muscle throughout course disease many cases accompanied obesity related inflammation nonetheless consuming epigallocatechin gallate egcg ketone bodies especially hydroxybutyrate hb produced metabolising coconut oil exhibited antiinflammatory effects decrease body fat addition butyrylcholinesterase buche seems related pathogenesis disease associated inflammation serum concentrations related lipid metabolism objective aim study determine role buche changes caused treatment egcg ketone bodies levels body fat inflammation state ms patients 2 methods pilot study conducted 4 months 51 ms patients randomly divided intervention group control group intervention group received 800 mg egcg 60 ml coconut oil control group prescribed placebo fat percentage concentrations butyrylcholinesterase enzyme buche paraoxonase 1 pon1 activity triglycerides interleukin 6 il6 albumin hb serum measured 3 results intervention group exhibited significant decreases il6 fat percentage significant increases buche hb pon1 albumin functional capacity determined expanded disability status scale edss hand control group exhibited decrease il6 intervention buche positively correlated activity pon1 fat percentage triglycerides intervention group whereas correlations observed control group 4 conclusions buche seems important role lipolytic activity inflammation state ms patients evidenced administering egcg coconut oil hb sourcepmid34579104 doi103390 nu13093230,0.0
swadapt1 assessment electric wheelchairdriving robotic module standardized circuits prospective controlled repeated measure design pilot study abstractobjectivesthe objective study highlight effect robotic driver assistance module powered wheelchair pwc using infrared sensors accessorizing commercial wheelchair reduction number collisions standardized circuit population neurological disorders comparing driving performance without assistancemethodsthis prospective singlecenter controlled repeated measure design singleblind pilot study including patients neurological disabilities usual drivers electric wheelchairs main criterion evaluating device number collisions without assistance prototype anticollision system three circuits increasing complexity travel times cognitive load driving performance user satisfaction also analyzedresults23 patients 11 women 12 men mean age 48 years old completed study statistically significant reduction number collisions complex circuit 61 experienced collisions without assistance versus 39 assistance p 0038 conclusionthis study concludes pwc driving assistance module efficient terms safety without reducing speed movement population people disabilities habitual wheelchair drivers prospects therefore conduct tests target population driving failure difficulty benefit device allow travel independently safely,0.0
assessment multiple sclerosis awareness knowledge among community jeddah saudi arabia j neurosci rural pract 2021 sep 16 12 4 733738 doi 101055 s00411734009 ecollection 2021 octabstractobjective multiple sclerosis ms degenerative disease central nervous system can lead lifelong disabilities significant increase global incidence disease saudi arabia sa western region greatest number ms cases however lack studies research assess public knowledge region thus aim assess publics knowledge ms jeddah sa methodology conducted crosssectional study surveying 468 participants general population jeddah validated ms knowledge questionnaire mskq25 used results participants female 347 741 mean age 3573 1471 standard deviation sd ms found 14 3 participants average score mskq 742 sd 4568 versus average score people ms mean 1392 sd 333 p value 0001 significant variation found knowledge gender age groups significant correlation educational level knowledge level conclusion mean knowledge score average indicates poor knowledge ms since western region highest number ms cases sa level understanding needs increase can improved conducting educational programs using various types mediapmid34737508 pmcpmc8559084 doi101055 s00411734009,0.0
blood biomarkers mild traumatic brain injury selective review unresolved issues background use blood biomarkers mild traumatic brain injury mtbi widely studied identified eight unresolved issues related use five commonly investigated blood biomarkers neurofilament light chain ubiquitin carboxyterminal hydrolasel1 tau s100b glial acidic fibrillary protein conducted focused literature review unresolved issues three areas mode entry exit blood kinetics blood biomarkers blood predictive capacity blood biomarkers mtbifindingsalthough disruption blood brain barrier demonstrated mild severe traumatic brain injury biomarkers can enter blood pathways require breach barrier definitive accounting pathways biomarkers follow brain blood mtbi performed although preliminary investigations blood biomarkers kinetics tbi available current knowledge incomplete definitive studies needed optimal sampling times biomarkers mtbi established kinetic models blood biomarkers can informative precise estimates kinetic parameters needed confounding factors blood biomarker levels identified corrections factors routinely made little evidence emerged date suggest blood biomarker levels correlate clinical measures mtbi severity significance elevated biomarker levels thirty days following mtbi uncertain blood biomarkers shown modest definitive ability distinguish concussed nonconcussed subjects detect subconcussive hits head predict recovery mtbi blood biomarkers performed best distinguishing ct scan positive ct scan negative subjects mtbi,0.0
role bet proteins inflammation cns diseases front mol biosci 2021 sep 16 8748449 doi 103389 fmolb2021748449 ecollection 2021abstractbromodomain extraterminal domain bet proteins consist four mammalian members brd2 brd3 brd4 brdt play pivotal role transcriptional regulation inflammatory response dysregulated inflammation key pathological process various cns disorders multiple mechanisms including nfb nrf2 pathways two wellknown master regulators inflammation better mechanistic understanding bet proteins role regulating inflammatory process great significance since reveal novel therapeutic targets reduce neuroinflammation associated many cns diseases minireview first outline structural features bet proteins summarize genetic pharmacological approaches bet inhibition including novel strategies using proteolysistargeting chimeras protacs emphasize vitro vivo evidence interplay bet proteins nfb nrf2 signaling pathways finally summarize recent studies showing bet proteins essential regulators inflammation neuropathology various cns diseasespmid34604312 pmcpmc8481655 doi103389 fmolb2021748449,0.0
acute retinal necrosis caused coinfection multiple viruses natalizumabtreated patient case report brief review literature background acute retinal necrosis considered rare infectious uveitis condition usually caused varicellazoster virus herpes simplex virus acute retinal necrosis caused coinfection multiple viruses extremely rare herein report case acute retinal necrosis caused coinfection herpes simplex virus type ii varicellazoster virus vzv natalizumabtreated patient due multiple sclerosiscase presentationan adult man presented complaint decreased vision right eye 12 days ago known case multiple sclerosis receiving natalizumab examination right eye revealed severe conjunctival injection fine diffuse keratic precipitates 3 + anterior chamber vitreous cells elevated intraocular pressure 26 mmhg blurred optic disk hemorrhagic patches occlusive vasculitis plus confluent necrotizing patches peripheral retina compatible diagnosis acute retinal necrosis underwent anterior chamber vitreous tap realtime pcr detected hsv ii vzv vitreous specimen second pcr showed result neurological consultation natalizumab discontinued intravenous acyclovir started followed oral acyclovir oral prednisolone control disease successfulconclusionsalthough rare multipleviral infection considered physiopathology acute retinal necrosis especially immunosuppressed patients,0.0
1 25dihydroxyvitamin d3 protects retinal ganglion cells glaucomatous mice background glaucoma optic neuropathy characterized loss function death retinal ganglion cells rgcs leading irreversible vision loss neuroinflammation recognized one causes glaucoma currently treatment addressing mechanism aimed investigate antiinflammatory neuroprotective effects 1 25 oh 2d3 1 25dihydroxyvitamin d3 calcitriol genetic model agerelated glaucomatous neurodegeneration dba 2j mice methodsdba 2j mice randomized 1 25 oh 2d3 vehicle treatment groups pattern electroretinogram flash electroretinogram intraocular pressure recorded weekly immunostaining rbpms iba1 gfap carried retinal flat mounts assess retinal ganglion cell density quantify microglial astrocyte activation respectively molecular biology analyses carried evaluate retinal expression proinflammatory cytokines pnfbp65 neuroprotective factors investigators analysed data blind experimental groups unveiled graph design statistical analysis carried graphpad prism several statistical tests approaches used generalized estimated equations gee analysis ttest oneway anovaresultsdba 2j mice treated 1 25 oh 2d3 5 weeks showed improved perg ferg amplitudes reduced rgcs death compared vehicletreated agematched controls 1 25 oh 2d3 treatment decreased microglial astrocyte activation well expression inflammatory cytokines pnfbp65 p 005 moreover 1 25 oh 2d3treated dba 2j mice displayed increased mrna levels neuroprotective factors p 005 bdnfconclusions1 25 oh 2d3 protected rgcs preserving retinal function reducing inflammatory cytokines increasing expression neuroprotective factors therefore 1 25 oh 2d3 attenuate retinal damage glaucomatous patients warrants clinical evaluation treatment optic neuropathies,1.0
fiveyear follow original irish bicams validation cohort abstractintroduction cognitive impairment common multiple sclerosis stages condition natural history cognition multiple sclerosis considered deterioration cognitive functioning time development brief international cognitive assessment multiple sclerosis bicams allowed standardization screening tool cognitive impairment can easily performed neurology clinic crosssectional validation studies using bicams widely reported however minimal longitudinal assessment cognition using bicams taken place dateobjectives objective study evaluate prevalence cognitive impairment fiveyear interval participants original bicams validation study will also evaluate change bicams subtests timematerials methods participants original bicams validation study invited participate study demographic clinical details collected bicams subtests anxiety depression fatigue questionnaires completedresults fifty original 67 participants completed bicams five years post original assessment prevalence cognitive impairment cohort mean age 49 median edss 25 edss 20 initial bicams testing remained stable five years following initial bicams screening assessment x2 1 036 p0548 significant difference sdmt scores 2014 2019 t 48 108 p015 improvement cvltii t 49 303 p004 bvmtr t 49 338 p001conclusions study demonstrates overall stability prevalence cognitive impairment assessed bicams interval five years assessment reduces possibility practice effects although familiarity testing protocol may exert influence,0.0
neuromyelitis optica spectrum disorders pathophysiology therapeutic strategies abstractneuromyelitis optica nmo chronic inflammatory autoimmune disease central nervous system cns characterized acute optic neuritis transverse myelitis tm nmo caused pathogenic serum igg antibody water channel aquoporin 4 aqp4 majority patients aqp4antibody aqp4ab presence highly specific differentiates nmo multiple sclerosis binds aqp4 channels astrocytes triggering activation classical complement cascade causing granulocyte eosinophil lymphocyte infiltration culminating injury first astrocyte oligodendrocytes followed demyelination neuronal loss nmo spectrum disorder nmosd recently defined stratified based aqp4ab serology status nmosd patients experience severe relapses leading permanent neurologic disability making suppression relapse frequency severity primary objective disease management common treatments used relapses steroids plasma exchangecurrently longterm nmosd relapse prevention includes offlabel use immunosuppressants particularly rituximab last 2 years however three pivotal clinical trials expanded spectrum drugs available nmosd patients phase iii studies shown significant relapse reduction compared placebo aqp4abpositive patients treated satralizumab interleukin6 receptor il6r inhibitor inebilizumab antibody cd19+ b cells eculizumab antibody blocking c5 component complement light new evidence nmosd pathophysiology preliminary results ongoing trials new drugs present descriptive review highlighting promising treatment modalities well auspicious preclinical clinical studies,1.0
correlation vitamin d alterations mri among patients multiple sclerosis ann agric environ med 2021 sep 16 28 3 372377 doi 1026444 aaem 127062 epub 2020 sep 17abstractintroduction multiple sclerosis ms disease unknown etiology diagnosis ms primarily based detection myelin damage magnetic resonance imaging mri classification demyelination according mcdonald criteria cholecalciferol vitamin d3 shown affect onset progression ms via immunomodulating properties role vitamin d ms pathogenesis treatment deserves investigation sufficient evidence suggest correlation vitamin d blood level brain mri lesion loadstate knowledge elevated blood vitamin d concentration linked demyelination determined t2weighted gadoliniumenhanced mri blood vitamin d blood levels affected sun exposure among factors however evident connection abnormalities myelination seasonality vitamin d supplementation among ms patients associated lower probability new lesions loss existing lesion volume observed seen t1weighted mri scans p003 increase tgfbeta levels noted among patients using vitamin d supplementation may suggest mechanism cholecalciferol may improve ms prognosis patients clinically isolated syndrome cis exhibited inverse correlation vitamin d concentration risk new lesions seen t2weighted mri scans moreover vitamin d intake among patients lowered risk progression clinically definite multiple sclerosis cdms daily intake vitamin d fingolimod treatment correlated strongly lower numbers new lesions high dose vitamin d supplementation interferon beta1a treatment linked lower mean percentage lesions compared volume pretreatment seen t2weighted mriresults recent findings advocate monitoring vitamin d blood levels ms patients vitamin d supplementation considered ms patients patients cis signs disease may delayed moreover vitamin d supplementation appears lower likelihood new demyelination changes apparent mri examinationspmid34558256 doi1026444 aaem 127062,1.0
regulatory t cells protect brain damage alleviating inflammatory response neuromyelitis optica spectrum disorder background purposeneuromyelitis optica spectrum disorder nmosd mainly antiaquaporin 4 antiaqp4 autoantibodiesmediated idiopathic inflammatory demyelinating disease central nervous system systemic local inflammatory responses play key role pathophysiology nmosd however role crucial immunomodulators cd4+cd25+ forkhead box p3+ foxp3 regulatory t cells tregs investigated nmosdmethodstwentyfive patients antiaqp4postive nmosd undergoing attack 21 healthy controls hcs enrolled frequencies t cell subsets tregs peripheral blood assessed flow cytometry additionally model nmosd using purified immunoglobulin g antiaqp4antibodiespositive patients nmosd human complement injected brain female adult c57bl 6j mice established infiltrated tregs nmosd mouse brain lesions analyzed flow cytometry histological sections realtime quantitative polymerase chain reaction astrocyte loss demyelination inflammatory response also evaluated nmosd mouse model finally examined effects depletion adoptive transfer tregsresultsthe percentage tregs especially nave tregs among total t cells peripheral blood significantly decreased nmosd patients acute stage compared hcs within animal model number proportion tregs among cd4+ t cells increased lesion mice nmosd depletion tregs profoundly enhanced astrocyte loss demyelination mice adoptive transfer tregs attenuated brain damage mechanistically absence tregs induced macrophage infiltration microglial activation t cells invasion modulated macrophages microglia toward classical activation phenotype releasing chemokines proinflammatory cytokines contrast tregs transfer ameliorated immune cell infiltration nmosd mice including macrophages neutrophils t cells skewed macrophages microglia towards alternative activation phenotype thereby decreasing level chemokines proinflammatory cytokinesconclusiontregs may key immunomodulators ameliorating brain damage via dampening inflammatory response nmosd,1.0
aseptic meningitis leptomeningeal enhancement associated antimog antibodies review j neuroimmunol 2021 jul 1 358577653 doi 101016 jjneuroim2021577653 online ahead printabstractbackground aseptic meningitis can caused autoimmune diseases lupus sarcoidosis aseptic meningitis leptomeningeal enhancement can initial presentation neuroinflammatory syndrome associated antibodies myelin oligodendrocyte glycoprotein mogabs mogabs serum biomarker mogassociated disorder mogad acquired demyelinating syndrome includes features neuromyelitis optica multiple sclerosis optic neuritis acute disseminated encephalomyelitis purpose study review cases aseptic meningitis leptomeningeal enhancement associated mogabsmethods systematic review using pubmed embase ovid medline web science core collection google scholar december 2020 performed cases mogad included met following criteria 1 initial clinical presentation aseptic meningitis 2 positive leptomeningeal enhancement 3 mogab seropositivity descriptive statistics used analysis limited cases available literatureresults 11 total cases aseptic meningitis leptomeningeal enhancement setting mogab identified demyelinating type t2 lesions also present time presentation 6 11 however 5 11 patients leptomeningeal enhancement alone without demyelinating lesions 5 patients required immunotherapy improvement including one patient symptoms 28 days 4 5 receiving steroids 1 5 receiving intravenous immunoglobulin ivig conclusions aseptic meningitis leptomeningeal enhancement can initial presenting symptom mogad mogab testing considered patient presenting aseptic meningitis leptomeningeal enhancement unknown etiologypmid34229204 doi101016 jjneuroim2021577653,1.0
loss elp1 perturbs histone h2az notch signaling pathway biol open 2021 sep 15 10 9 bio058979 doi 101242 bio058979 epub 2021 sep 30abstractelongator dysfunction increasingly recognized contributor multiple neurodevelopmental neurodegenerative disorders including familial dysautonomia intellectual disability amyotrophic lateral sclerosis autism spectrum disorder although numerous cellular processes perturbed context elongator loss converging evidence multiple studies resolved elongators primary function cell modification trna wobble uridines translational regulation codonbiased genes characterize h2az encoding variant h2a histone h2az indirect elongator target show canonical notch signaling pathway directed h2az perturbed consequence elp1 loss finally demonstrate hyperacetylation h2az histones via exposure histone deacetylase inhibitor trichostatin neurogenesis corrects expression notch3 rescues development sensory neurons embryos lacking elp1 elongator subunitpmid34590699 doi101242 bio058979,0.0
prognostic factors tumefactive demyelinating lesions retrospective study j neurol sci 2021 jul 27 428117591 doi 101016 jjns2021117591 online ahead printabstractintroduction demyelinating lesions occasionally present masslike lesions imaging raising concern malignancy disease course tumefactive demyelinating lesions tdls still definedmethods retrospectively analyzed 21 patients newonset neurologic symptoms masslike lesions brain magnetic resonance imaging mri resulted biopsyproven diagnoses demyelination 18 patients median followup 52 months clinical radiologic histologic features associated disease courseresults aggressive disease course adc noted 33 patients associated initial largest lesion size 35 mm p 00007 mass effect p 001 perilesional edema p 001 mri age 30 years older presentation p 005 well absence prior tonsillectomy p 00128 also associated adcconclusions identified several factors including initial larger lesion size mass effect perilesional edema mri presentation 30 years age absence prior tonsillectomy predict adc patients presenting tdls predictors disease course can help guide patient followup stratification interventionpmid34333380 doi101016 jjns2021117591,1.0
patients experiences selfidentification seeking support anticipation potential relapse multiple sclerosis abstractbackground multiple sclerosis ms relapses associated increased disability reduced quality life negative psychosocial impacts however often go unrecognised people ms msers may face barriers selfidentification relapses seeking support charity shiftms sought better understand 1 msers challenges selfidentifying potential relapses 2 msers seek support potential relapses 3 impact anticipation relapses msers wellbeing daily livingmethods shiftms developed patient perspective 8question pilot survey included likertstyle multiplechoice optional freetext responses shared shiftms international online community n20 052 descriptive quantitative analysis content analysis thematic analysis qualitative freetext responses usedresults 1 737 msers responded just one third 299 msers reported takes 24 hours less selfidentify potential relapse half 545 reported identification occurs within 48 hours 55 msers felt least 24 hours clinical criterion relapse classification appropriate challenges relapse selfidentification included confounding background symptoms infection variability relapse symptoms individualistic nature ms fatigue reported common symptom relapse 75 however fatigue also symptom commonly mistaken relapse 40 barriers relapse selfidentification shorter duration since ms diagnosis perceived lack consensus around relapse classification respondents reported often seek relapse support advice healthcare professionals hcps 371 family friends 321 169 rather temporal criteria ie 24 hour criterion participants felt severity symptoms play critical role whether seek support potential relapse barriers seeking support advice included variability hcp advice feelings invalidation anticipation relapses negatively impacted msers wellbeing led reduced participation activities development adjustment coping strategies relapse triggers included stress reduced selfcare infection illness 785 reported stress anxiety triggered relapseconclusions findings highlight difficulties msers face selfidentifying relapses barriers accessing support impact anticipation relapses also highlight opportunities improved mser hcp communication dialogue twoway education help optimise patient access relapse support intervention,0.0
impact iga microbiota cns disease front immunol 2021 sep 15 12742173 doi 103389 fimmu2021742173 ecollection 2021abstractalthough anatomically distant central nervous system cns gutderived signals can dynamically regulate peripheral immune cells cnsresident glial cells modulate disease recent discoveries specific microbial taxa microbial derived metabolites modulate neuroinflammation neurodegeneration provided mechanistic insight gut may modulate cns furthermore participation gut regulation peripheral cns immune activity introduces potential therapeutic target review addresses emerging literature microbiome can affect glia circulating lymphocytes preclinical models human cns disease critically review also discusses host may turn influence microbiome may impact cns homeostasis disease potentially production igapmid34603329 pmcpmc8479159 doi103389 fimmu2021742173,0.0
paroxysmal dysarthria ataxia unusual ms manifestation lakartidningen 2021 sep 15 11821022abstractmultiple sclerosis common inflammatory demyelinating disease central nervous system although many patients present permanent symptoms number suffer deficits paroxysmal character one unusual manifestation paroxysmal nature episodes dysarthria ataxia known pda paroxysmal dysarthria ataxia mechanism behind phenomenon although well understood hypothesised relate ephaptic activation neuroaxons within demyelination plaques just patients worldwide reported present symptoms can effectively treated antiseizure medicines present case female 48yearold patient shortly ms diagnosis developed paroxysmal dysarthria ataxia related midbrain lesion eventually treated carbamazepinepmid34524683,1.0
determinants maternal health four weeks delivery crosssectional findings kunokids health study background aim study examine interaction multitude socioeconomic lifestyle environmental psychosocial birth related determinants effect maternal health four weeks deliverymethodswe used data german birth cohort study kunokids health study social determinants well selfrated maternal health physical mental health status mothers indicated means sf12questionnaire assessed standardized questionnaires personal interviews right delivery four weeks later linear regression models calculated determine relationship influencing factors health outcomesresults1428 women included analysis maternal selfrated health showed significant positive associations breastfeeding b regression coefficient 267 086448 95 confidence interval estimating ones child rather healthy b 027 019034 negative associations social emotional strains b 350 511 188 obesity b 256 469 042 experienced csection b 173 323 023 positive history somatic diseases b 214 353 074 parental stress b 039 066 011 education ten years b 242 395 090 maternal physical health status showed significant negative associations age b 013 025 001 employment maternity leave b 190 359 021 social emotional strains b 150 267 034 parental stress b 028 045 012 csection b 406 512 299 first child b 203 309 097 history somatic diseases b 200 299 101 maternal mental health status showed significant positive associations education 10 years b 227 098356 high level social support b 120 006234 social emotional strains b 416 548 284 parental stress b 070 092 047 negatively associatedconclusionswe identified important protective factors maternal health four weeks delivery high level social support however parental stress social emotional strains particular seem negative influence maternal health findings public health relevance,0.0
herpesviruses hidden links multiple sclerosis neuropathology j neuroimmunol 2021 jun 19 358577636 doi 101016 jjneuroim2021577636 online ahead printabstractherpesviruses like epsteinbarr virus human herpesvirus hhv 6 hhv1 vzv human endogenous retroviruses ageold clinical association multiple sclerosis ms ms autoimmune disease nervous system wherein myelin sheath deteriorates popular mode virus mediated immune system manipulation molecular mimicry numerous herpesvirus antigens similar myelin proteins mechanisms described include activity cytokines autoantibodies produced autoreactive t b cells respectively viral dj vu epitope spreading cd46 receptor engagement impaired remyelination etc overall review addresses hostparasite association viruses mspmid34174587 doi101016 jjneuroim2021577636,1.0
postmortem diagnosis pulmonary tumor thrombotic microangiopathy rapid exacerbation patient gastric cancer case report background pulmonary tumor thrombotic microangiopathy pttm condition involves development pulmonary hypertension due presence microscopic tumor emboli peripheral pulmonary arteries report case rapidly exacerbating pttm associated gastric cancer identified postmortem pathological autopsycase presentationa 52yearold asian woman experienced anterior chest pain coughing visited orthopedic department gifu university hospital diagnosed multiple osteolytic bone metastases throughout body subsequently scheduled undergo combined positron emission tomography computed tomography ct search primary lesion however 4 days visit orthopedic department unable stand thus visited emergency department time admission physical examination results revealed percutaneous oxygen saturation level 90 room air cyanosis state hemodynamic shock laboratory test results revealed elevated levels fibrin degradation products ddimer blood chest ct results normal admitted hospitals general ward followup soon entered gradually worsening state shock respiratory failure electrocardiography revealed findings associated right heart strain however contrastenhanced ct reveal presence pulmonary embolism admitted intensive care unit treated pulmonary hypertension however 45 h arrival hospital died respiratory failure pathological autopsy revealed presence gastric cancer tumor microemboli fibrous intimal thickening peripheral arteries lungs thus diagnosis pttm madeconclusionsin patients carcinoma unknown primary site pulmonary hypertension pulmonary embolism ruled ct emergency physicians intensivists must consider possibility pttm represents oncologic emergency initiate chemotherapy administration soon possible,0.0
optimizing nutrition oral health caregiversintervention protocol background focus care shifted institutional care home care family caregivers provide majority home care allows opportunity care recipients live home avoid costly institutional care aim study describe nutritional status oral health quality life family caregivers age 65 care recipients evaluate impact individually tailored diet oral health advice nutritional status oral healthmethods designaltogether 250 family caregivers aged 65 care recipients studied prospective randomized populationbased multidisciplinary 6month intervention study participants randomly allocated intervention groups control group data collection performed three timepoints baseline 6 months 6month followup 12 months caregivers care recipients nutritional oral health status primary outcome functional ability cognitive status quality life depression symptoms sense coherence morbidity medication family caregivers secondary outcomes will measured using validated selfadministered questionnaires clinical examinationsdiscussionto knowledge first experiment determine whether caregivers care recipients benefit individual nutritional intervention oral health intervention terms nutrition status oral health status quality lifetrial registrationclinicaltrialsgov nct04003493 registered june 28 2019,0.0
balo#39 s concentric sclerosis rare entity within spectrum demyelinating diseases j neurol sci 2021 jul 7 428117570 doi 101016 jjns2021117570 online ahead printabstractbals concentric sclerosis bcs rare inflammatory demyelinating disease central nervous system cns historically bcs thought uniformly fatal diagnosis based postmortem findings advances modern neuroimaging bcs currently defined presence concentric layered patterns composed alternating rings varying intensity best appreciated gadoliniumenhanced t1weighted sequences predominantly occur supratentorial cerebral white matter sparing cortical ufibers lamellar pattern lesions likely reflects bands demyelination relative myelin preservation minimal axonal loss bcs falls within spectrum atypical demyelinating diseases ongoing debate whether bcs phenotypical variant multiple sclerosis ms separate entity corticosteroids comprise firstline therapy ongoing controversy regarding appropriate maintenance therapy firstline ms diseasemodifying therapies interferon beta1a appropriate patients fulfill diagnostic criteria relapsingremitting ms fingolimod likely avoided ballike lesions reported administration withdrawal monoclonal antibodies natalizumab rituximab potentially effective reducing bcs relapses alemtuzumab may relatively ineffective humoral immunity play central role bcs pathogenesispmid34261000 doi101016 jjns2021117570,1.0
evaluation swallow tail sign patients parkinsonism gait disorders j neurol sci 2021 jul 14 428117581 doi 101016 jjns2021117581 online ahead printabstractbackground swallow tail sign sts represents nigrosome1 substantia nigra 3 tesla t susceptibilityweighted imaging swi attracted attention promising magnetic resonance imaging mri biomarker idiopathic parkinsons disease ipd reports shown high sensitivity specificityboth 94for distinguishing ipd healthy controls however abnormal sts observed many neurodegenerative parkinsonisms even multiple sclerosismethods patients parkinsonism 3 t mri included retrospective chart review single movement disorders clinic subjects evaluated single movement disorder specialist using movement disorders society diagnostic criteria american academy neurology consensus guidelines diagnoses mris interpreted single neuroradiologist blinded diagnosisresults twenty patients included study twelve abnormal sts ipd n 2 probable multiple system atrophy n 3 vascular parkinsonism n 1 psychogenic gait disorder n 1 neuroleptic parkinsonism n 2 cervical dystonia n 1 static encephalopathy n 1 gait disorder unknown etiology n 1 eight normal sts ipd n 1 probable progressive supranuclear palsy n 1 vascular parkinsonism n 2 transient parkinsonism unknown etiology n 2 valproic acid induced parkinsonism n 1 essential tremor parkinsonism n 1 123iioflupane spect dopamine transporter dat scan results available seven subjects four subjects incongruency dat mriconclusion results suggest abnormal sts isolation reliable biomarker idiopathic parkinsons diseasepmid34333378 doi101016 jjns2021117581,0.0
pathogenic therapeutic diagnostic role exosomal microrna autoimmune diseases j neuroimmunol 2021 jun 24 358577640 doi 101016 jjneuroim2021577640 online ahead printabstractexosomes nanovesicle surrounded bilipid layer can release almost cells detected tissues biological liquids vesicles contain lipids proteins nucleic acids including dna mrna mirna inside exosomes surface constitute content exosomes can transfer cargo recipient cell can modify recipient cells biological activities recently deciphering mirna pattern exosomes reveals cellular pathophysiological situation modifies various biological processes increasing data regarding exosomes highlights exosomes cargo especially mirnas implicated pathophysiology various disorders autoimmune disease current evidence deciphering mechanisms exosomal mirnas contributed autoimmunity indicated exosomal mirna might hold information can reprogram function many immune cells involved autoimmune diseases pathogenesis present study summarized pathogenic role exosomal mirnas several autoimmune diseases including myasthenia gravis mg psoriasis inflammatory bowel disease ibd type 1 diabetes t1d multiple sclerosis ms systemic lupus erythematosus sle rheumatoid arthritis ra sjogrens syndrome ss systemic sclerosis ssc vitiligo autoimmune thyroid diseases aitd moreover work present evidence potential role exosomal mirnas therapeutic diagnostic agents autoimmune diseasespmid34224949 doi101016 jjneuroim2021577640,0.0
phosphodiesterase 7 pde7 unique drug target central nervous system diseases neuropharmacology 2021 jul 7108694 doi 101016 jneuropharm2021108694 online ahead printabstractphosphodiesterase 7 pde7 one 11 phosphodiesterase pde families specifically hydrolyzes cyclic 3 5adenosine monophosphate camp pde7 involved many important functional processes physiology pathology regulating intracellular camp signaling studies demonstrated pde7 widely expressed central nervous system cns potentially related pathogenesis many cns diseases summarized classification distribution pde7 brain functional roles mediation cns diseases parkinsons disease pd alzheimers disease ad multiple sclerosis ms schizophrenia expected findings collected will lead better understanding mechanisms pde7 mediates cns function diseases also aid development novel drugs targeting pde7 treatment cns diseasespmid34245775 doi101016 jneuropharm2021108694,1.0
proportions circulating transitional b cells associate mri activity interferon betatreated multiple sclerosis patients j neuroimmunol 2021 jul 14 358577664 doi 101016 jjneuroim2021577664 online ahead printabstractbcells contribute ms pathogenesis association circulating bcell phenotypes combined unique active lesions cua mri 48 weeks followup investigated 50 interferon betatreated ms patients transitional bcell proportions lower participants cua week 0 48 p 0004 p 0002 decrease circulating antiebna1 igg levels week 0 48 associated absence cua p 0047 bcell profiles multifactor model cuarisk transitional bcell proportions contributed independent nk tcell ratio change antiebna1 igg vitamin d supplementation transitional bcells may predict treatment response mspmid34280843 doi101016 jjneuroim2021577664,0.0
analysis risk factors perioperative hidden blood loss unilateral biportal endoscopic spine surgery retrospective multicenter study background hidden blood loss hbl represents important complication unilateral biportal endoscopic ube spine surgery study aimed evaluate hbl possible risk factors among patients undergoing ube surgery lumbar degenerative diseasesmethodsthis multicentric retrospective study conducted 3 different medical centers july 2020 april 2021 data patients underwent ube surgery extracted electronic medical record system patients demographic characteristics blood lossrelated parameters recorded calculated amount hbl explored association patients characteristics hbl using pearson spearman correlation analysis multivariate linear regression analysis conducted identify independent risk factors hblresultsa total 136 patients 55 females 81 males age range 43 74 years included study substantial amount hbl 4695 1953 ml 576 tbl total blood loss occurred following ube surgery multiple linear regression analysis indicated risk factors hbl follows age p 0000 number fusion levels p 0015 american society anesthesiologists asa classification p 0046 surgery time p 0017 patients blood volume pbv p 0026 total blood loss tbl p 0001 postoperative ie day 2 3 hematocrit hct p 0034 hct loss p 0005 fibrinogen p 0028 conclusionsa certain amount hbl occurs ube surgery ignored daily clinical practice age number fusion levels asa classification surgery time pbv tbl postoperative hct hct loss fibrinogen independent risk factors hbl,0.0
electronic pill bottles monitor promote medication adherence people multiple sclerosis randomized virtual clinical trial j neurol sci 2021 aug 8 428117612 doi 101016 jjns2021117612 online ahead printabstractobjective perform randomized trial test impact electronic pill bottles audiovisual reminders oral disease modifying therapy dmt adherence people ms pwms methods adults multiple sclerosis ms taking oral dmt randomized 11 90 days remote smartphone app pill bottlebased adherence monitoring b adherence monitoring audiovisual medication reminders optimal adherence defined proportion doses taken 3 h scheduled time numbers missed pills pills taken early time late extra recorded multivariable regression model tested possible associations optimal adherence age ms duration cognitive functioning number daily prescription pillsresults 85 participants 66 female mean age 449 years took dimethyl diroximel fumarate n 49 fingolimod n 26 teriflunomide n 10 optimal adherence average higher monitoring reminders arm 714 monitoring arm 616 p 0033 multivariable model optimal adherence less likely younger participants p 0001 taking daily prescription pills p 0001 monitoring arm 40 doses taken early 616 time 56 late 44 excess 244 missed reminders arm proportions 34 714 37 87 128 respectivelyconclusion map realworld oral dmt adherence patterns using mhealth technology pwms received medication reminders higher optimal adherence nonadherence nuanced simply missing pills developing strategies improve adherence remains important longitudinal ms carepmid34392138 doi101016 jjns2021117612,0.0
analysis genes tmem106b grn abcc9 kcnmb2 apoe implicated risk latenc hippocampal sclerosis provides pathogenetic insights retrospective genetic association study abstractlimbicpredominant agerelated tdp43 encephalopathy neuropathologic change latenc prevalent subtype tdp43 proteinopathy affecting 1 3rd aged persons latenc often cooccurs hippocampal sclerosis hs pathology currently unknown individuals latenc develop hs others genetics may play role previous studies found associations latenc phenotypes specific genes tmem106b grn abcc9 kcnmb2 apoe data research participants genomic autopsy measures national alzheimers coordinating center nacc n 631 subjects included religious orders study memory rush aging project rosmap n 780 included analyzed current study goals reevaluate diseaseassociated genetic variants using newly collected data query whether specific genotype phenotype associations provide new insights diseasedriving pathways research subjects included prior late hs genomewide association studies gwas excluded single nucleotide variants snvs within 10 kb tmem106b grn abcc9 kcnmb2 apoe tested association hs latenc separately alzheimers pathologies ie amyloid plaques neurofibrillary tangles significantly associated snvs identified results metaanalyzed tmem106b grn apoe significant genebased associations late hs whereas abcc9 significant associations hs sensitivity analysis limited latenc + cases abcc9 variants associated hs contrast associations tmem106b grn apoe hs attenuated adjusting tdp43 proteinopathy indicating genes may associated primarily tdp43 proteinopathy none genes except apoe appeared associated alzheimerstype pathology summary using data included prior studies late hs genomics replicated several previously reported genebased associations found novel evidence specific risk alleles can differentially affect latenc hs,0.0
ebi2expressing b cells neuromyelitis optica spectrum disorder aqp4igg association acute attacks serum cytokines j neuroimmunol 2021 jun 22 358577637 doi 101016 jjneuroim2021577637 online ahead printabstractepsteinbarr virusinduced gprotein coupled receptor 2 ebi2 important regulating b cell activation investigated whether ebi2 expression b cells associated acute attacks neuromyelitis optica spectrum disorder aquaporin4 igg aqp4igg + nmosd blood samples collected patients aqp4igg + nmosd multiple sclerosis ms patients without inflammatory demyelinating diseases nonidd controls cd19+ b cells cd4+ t cells analyzed surface expression ebi2 serum cytokine levels also analyzed ebi2+cd19+ ebi2cd19+ cell ratio significantly higher patients aqp4igg + nmosd enrolled within 2 months attack nonidds p 0007 ms p 0003 patients aqp4igg + nmosd enrolled within 2 months attack higher ebi2+cd19+ cell frequency patients aqp4igg + nmosd enrolled 2 months recent attack p 0001 ebi2+cd19+ cell frequency positively correlated interleukin il 6 il10 ebi2 expression b cells associated acute attacks aqp4igg + nmosd possibly il6 il10related pathwayspmid34229205 doi101016 jjneuroim2021577637,1.0
different neuroinflammatory gene expression profiles highly active benign multiple sclerosis j neuroimmunol 2021 jul 2 358577650 doi 101016 jjneuroim2021577650 online ahead printabstractin study aimed explore expression genes associated neuroinflammation patients benign highly active multiple sclerosis ms healthy controls define gene signatures associated ms well disease activity progression identified differences expression 89 genes benign highly active ms patients healthy controls q 005 twentyeight genes related myeloid cells function innate immune response apoptosis autophagy differentially expressed patients benign highly active ms time second relapse expanded disability status scale edss scores correlated expression genes associated myeloid cells function innate immunity apoptosis results indicate importance innate immunityassociated pathways maintaining high disease activity ms crucial role disease progressionpmid34274720 doi101016 jjneuroim2021577650,0.0
family perspectives clinical research pediatric multiple sclerosis enhancing equity j patient exp 2021 sep 15 823743735211039319 doi 101177 23743735211039319 ecollection 2021abstractpediatric new drug trials federally mandated family perspectives multiple sclerosis ms research limited due ms chronicity longterm medical system involvement obtained family views research priorities optimized methods future studies focus groups convened families impacted pediatriconset ms recruitment included followed network pediatric ms centers geographically disparate locations centers voluntary election study questions included healthcare experiences clinical trials perspectives cognitive psychosocial educational outcomes disease course disability accrual subjects supported future clinical studies patients highlighted contribution knowledge base wary experimental medication diseasecourse impeding activities parents underscored medication delivery modalities sideeffects limiting childrens discomfort wanted study relevance made explicit suggested future study design elements included providing compensation limiting assumptions regarding outcome linkages understanding studyrelated psychological impacts reducing participation burdens rare disease research can assist general medicine diagnosis referral variable study designs explicit rationale may augment participation closing pediatric research gap requires family engagement research processpmid34541304 pmcpmc8447100 doi101177 23743735211039319,0.0
assessing usability wearable devices measure gait physical activity chronic conditions systematic review background world health organisations global strategy digital health emphasises importance patient involvement understanding usability acceptability wearable devices core component however usability assessments date focused predominantly healthy adults need understand patient perspective wearable devices participants chronic health conditionsmethodsa systematic review conducted identify study design included usability assessment wearable devices measure mobility gait physical activity within five cohorts chronic conditions parkinsons disease pd multiple sclerosis ms congestive heart failure chf chronic obstructive pulmonary disorder copd proximal femoral fracture pff resultsthirtyseven studies identified substantial heterogeneity quality reporting methods used assess usability devices used aims studies precluded meaningful comparisons questionnaires used majority studies 703 n 26 reliance intervention specific measures n 16 615 used interviews n 17 459 topic guides provided methods analysis reported third studies n 6 353 conclusionusability wearable devices poorly measured reported variable chronic health conditions although heterogeneity devices implemented implies acceptance patient voice assumed absence able make specific usability conclusions results review instead recommends future research needs 1 conduct usability assessments standard irrespective cohort investigation type study undertaken 2 adhere basic reporting standards eg coreq including basic details study full copies questionnaires interview guides supplied supplemental files 3 utilise mixed methods research gather comprehensive understanding usability either qualitative quantitative research alone will provide 4 use previously validated questionnaires alongside intervention specific measures,0.0
vitamin d status proinflammatory cytokines bone mineral density mexican people multiple sclerosis abstractbackgroundvitamin d vd classically associated calcium homeostasis bone mineral density since key role mineralization resorption immunomodulatory effects attributable vd low concentrations vd associated elevation inflammatory markers inflammatory autoimmune diseases multiple sclerosis ms chronic neurodegenerative suffering whose etiology still unknown directly related increase proinflammatory cytokines interleukin 17 interleukin 1 play important role physiopathology nowadays even though additional studies linked msnulls clinical signs low vd concentration scarce information association people regions sufficient sun exposure aim study evaluate serum vd cytokine concentrations bone density mexican people msmethodsvitamin d 25ohd interleukin 1 interleukin 6 interleukin 17 concentrations twentyfive volunteers ms determined enzymelinked immunosorbent assay bone mineral density body composition assessment performed dual energy xray absorptiometryresultsa mean concentration 17346 ng ml 25ohd obtained range 515 2571 ng ml international advisory bodies thresholds applied 76 participants exhibited degree vd inadequacy proinflammatory markers detectable among participants interleukin 1 100 interleukin 6 64 whereas interleukin 17 found 24 volunteers bone mineral density expected age found 8 participants lumbar spine affected anatomic region nonsignificant correlations found vd bone mineral density zscore proinflammatory markersconclusionalthough nonsignificant correlations found vd bone mineral density cytokines important highlight important percentage participants exhibited degree vd inadequacy unknown fact since included routine clinical evaluations low concentrations vd among sample regardless annual uvb sun exposure may suggest involvement endogenous environmental factors works needed order deepen physiological causes effects vd deficiency people ms,0.0
implantable device treat multiple sclerosis discrete choice experiment patient preferences three european countries j neurol sci 2021 jul 24 428117587 doi 101016 jjns2021117587 online ahead printabstractbackground persons multiple sclerosis ms take treatment via pills injections infusions novel mode diseasemodifying treatment administration implantable device development study determined ms patient preferences three modes firstline treatment administration implant pills injectables tradeoffs regarding treatment characteristicsmethods survey including discrete choice experiment conducted among ms patients netherlands france united kingdom respondents repeatedly choose various treatment scenarios four treatment characteristics risk relapse reduction disease progression risk side effects mode administration data analysed using panel latent class logit modelresults based preferences 753 ms patients response rate 7 753 11202 two latent classes identified class probability 74 vs 26 persons relapsingremitting ms administered medication via injections generally preferred treatment treatment patients walk without aid likely prefer treatment reducing disease progression important treatment characteristic class 1 mode administration important characteristic class 2 patients willing accept increase risk relapse disease progression get treatment via implant rather injections predicted uptake highest implant followed pills injections treatmentconclusion found drugdelivery implant potential addition ms treatment landscape ms patients willing tradeoff risk relapse disease progression implant predicted uptake implant relatively highpmid34364148 doi101016 jjns2021117587,0.0
ccr6 expression b cells required clinical pathological presentation mog proteininduced experimental autoimmune encephalomyelitis despite altered germinal center response j immunol 2021 aug 16ji2001413 doi 104049 jimmunol2001413 online ahead printabstractb cells implicated pathogenesis multiple sclerosis mechanisms guide b cell activation periphery subsequent migration cns remain incompletely understood previously showed systemic inflammation induces accumulation b cells spleen ccr6 ccl20dependent manner study evaluated role ccr6 ccl20 context myelin oligodendrocyte glycoprotein mog proteininduced b celldependent experimental autoimmune encephalomyelitis eae found ccr6 upregulated murine b cells migrate cns neuroinflammation addition human b cells migrate across cns endothelium vitro found ccr6+ detected ccl20 production activated cnsderived human endothelial cells well systemic increase ccl20 protein eae although mice lack ccr6 expression specifically b cells exhibited altered germinal center reaction response mog protein immunization ccr6deficient b cells exhibit competitive disadvantage migration cns eae clinical pathological presentation eae induced mog protein unaffected data knowledge provide new information role b cellintrinsic ccr6 expression b celldependent model neuroinflammationpmid34400521 doi104049 jimmunol2001413,1.0
occlusive retinal vasculitis associated systemic sclerosis antiphospholipid antibodies j ophthalmol case rep 2021 sep 15 24101206 doi 101016 jajoc2021101206 ecollection 2021 decabstractpurpose report series patients occlusive retinal vasculitis associated systemic sclerosis ssc elevated antiphospholipid antibody titersmethod case series main outcome measures included clinical fluorescein angiographic findings presentation timeobservations case 1 61yearold woman initially diagnosed idiopathic bilateral panuveitis retinal vasculitis causing peripheral nonperfusion subsequently diagnosed limited cutaneous systemic sclerosis lcssc ocular inflammation retinal vasculitis controlled topical periocular corticosteroids eventually developed peripheral retinal vascular occlusion progressed macular ischemia 11 years presentation repeat serologic evaluation detected interval development antiphospholipid antibodies case 2 58yearold woman found bilateral peripheral nonperfusion retinal neovascularization right eye given elevated hemoglobin a1c 85 diagnosed presumed proliferative diabetic retinopathy three years initial presentation diagnosed lcssc subsequent serum workup detected elevated b2glycoprotein antibody titers peripheral nonperfusion progressed despite adequate glycemic control resulting neovascularization eye case 3 40yearold woman diffuse cutaneous systemic sclerosis dcssc elevated titers anticardiolipin antibodies developed multiple branch retinal artery occlusions subsequent neovascularization retina optic disc angle right eyeconclusion importance visionthreatening occlusive retinal vasculitis may develop select patients ssc presence elevated antiphospholipid antibody titers may confer increased risk visionthreatening complicationpmid34568641 pmcpmc8449073 doi101016 jajoc2021101206,0.0
application her2 peptide vaccines patients breast cancer systematic review metaanalysis background e75 gp2 vaccines therapeutic vaccines targeting her2 currently clinical research patients breast cancermethodsdatabases including cochrane library pubmed medline embase web science used retrieve clinical studies e75 gp2 vaccines retrieval time beginning database construction may 31st 2021resultsa total 24 clinical studies included analysis including 1704 patients vaccinated group 1248 patients control group e75 vaccine significant differences vaccinated group control group delayedtype hypersensitivity reaction smd 0685 95 ci 052085 pheterogeneity 0186 pdth 005 change cd8+ tcell numbers smd 0864 95 ci 102 0709 pheterogeneity 0085 pcd8+ t cell 005 injection gp2 vaccine significant difference vaccinated group control group change cd8+ tcell numbers smd 0584 95 ci 0803 0294 pheterogeneity 0397 pcd8+ t cell 005 injection addition clinical outcomes including recurrence rate rr 0568 95 ci 04440727 pheterogeneity 0955 precurrence 005 diseasefree survival rate rr 1149 95 ci 10501256 pheterogeneity 0003 pdfs 005 e75vaccinated group different control group however found overall survival rate e75 vaccine rr 1032 95 ci 09981067 pheterogeneity 0476 pos 005 different two groups local systemic toxicity assessments two vaccines showed minimal side effectsconclusionsthe e75 vaccine effective safe patients breast cancer gp2 vaccine elicit strong immune response trials needed confirm clinical efficacy,0.0
patientreported burden symptoms neuromyelitis optica secondary analysis pain quality life j neurol sci 2021 jun 19 428117546 doi 101016 jjns2021117546 online ahead printabstractintroduction relapses neuromyelitis optica spectrum disorder nmosd result cumulative neurologic disabilities unpredictable interspersed remissions pain nmosd often severe intractable significant impact patient quality life qol performed detailed analysis previously published survey data association pain qol comparing patients seropositive seronegative antibodies aquaporin4 aqp4igg methods conducted secondary analysis questionnaire data 193 nmosd patients across north america study population predominantly female 886 aged 1976 years results reported three groups aqp4iggseropositive 611 aqp4iggseronegative total cohort including patients unknown serostatus measured strength associations interactions pain variables including qol patient satisfaction frequency hospital visits number relapses versus symptomsresults pain severity strongest negative predictor qol total aqp4iggseropositive groups pain common symptom patients wanted physician concerned aqp4iggseronegative group fatigue patients frequent hospital visits relapses associated severe pain frequency nmosd specialist visits patients without recent relapse still commonly reported moderate severe pain 25 conclusion study confirms heavy burden pain nmosd patients effect qol healthcare utilization prevention early treatment relapses effective pain management may reduce burdenpmid34252701 doi101016 jjns2021117546,0.0
chronic inflammationinduced senescence impairs immunomodulatory properties synovial fluid mesenchymal stem cells rheumatoid arthritis background although immunomodulatory properties mesenchymal stem cells mscs highlighted new therapy autoimmune diseases including rheumatoid arthritis ra diseasespecific characteristics mscs derived elderly ra patients well understoodmethodswe established mscs derived synovial fluid sf agematched early average duration disease 17 years longstanding average duration disease 138 years ra patients e lsfmscs analyzed msc characteristics stemness proliferation cellular senescence vitro differentiation vivo immunomodulatory propertiesresultsthe presence msc populations sf ra patients identified found lsfmscs exhibited impaired proliferation intensified cellular senescence reduced immunomodulatory properties attenuated antiarthritic capacity ra animal model particular esfmscs demonstrated cellular senescence progression attenuated immunomodulatory properties similar lsfmsc ra jointmimetic milieu due hypoxia proinflammatory cytokine exposure due longterm exposure chronic inflammatory milieu cellular senescence attenuated immunomodulatory properties loss antiarthritic potentials often identified sfmscs longterm ra early raconclusionwe conclude chronic ra inflammatory milieu affects msc potential therefore work addresses importance understanding msc characteristics disease states prior application patientsgraphical abstract,0.0
untargeted metabolomic profiling cuprizoneinduced demyelination mouse corpus callosum uplcorbitrap#x2f ms reveals potential metabolic biomarkers cns demyelination disorders oxid med cell longev 2021 sep 14 20217093844 doi 101155 2021 7093844 ecollection 2021abstractmultiple sclerosis ms neurodegenerative disorder characterized periodic neuronal demyelination leads range symptoms eventually disability goal research use uplcorbitrap ms identify validated biomarkers explore metabolic mechanisms ms mice thirtytwo c57bl 6 male mice randomized two groups fed either normal food 02 cpz 11 weeks mouse demyelination model assessed lfb expression mbp immunofluorescence immunohistochemistry metabolites corpus callosum quantified using uplcorbitrap ms mouse pole climbing experiment used assess coordination ability multivariate statistical analysis adopted screening differential metabolites ingenuity pathway analysis ipa used reveal metabolite interaction network successfully established demyelination model cpz group slowly lost weight showed increased pole climbing time feeding compared con group total 81 metabolites vip 1 p 005 determined enriched 24 metabolic pathways 41 metabolites markedly increased 40 metabolites markedly decreased cpz group ipa results revealed 81 biomarker metabolites associated neuregulin signaling pi3kakt signaling mtor signaling erk mapk signaling kegg pathway analysis showed two significantly different metabolic pathways enriched namely glycerophospholipid sphingolipid metabolic pathways comprising total nine biomarkers receiver operating characteristic analysis showed metabolites eg pe 16 0 22 6 4z 7z 10z 13z 16z 19z pc 18 0 22 4 7z 10z 13z 16z cytidine 5diphosphocholine ps 18 0 22 6 4z 7z 10z 13z 16z 19z glycerol 3phosphate sm d18 0 16 1 9z cer d181 18 0 galabiosylceramide d181 18 0 glccer d181 18 0 good discrimination ability cpz group conclusion differential metabolites great potential serve biomarkers demyelinating diseases addition identified metabolic pathways associated cpzinduced demyelination pathogenesis provided new perspective understanding relationship metabolites cns demyelination pathogenesispmid34567412 pmcpmc8457991 doi101155 2021 7093844,1.0
alterations sensorimotor mesiotemporal cortices diffuse white matter changes primary progressive multiple sclerosis detected adiabatic relaxometry front neurosci 2021 sep 14 15711067 doi 103389 fnins2021711067 ecollection 2021abstractbackground research primary progressive multiple sclerosis ppms able capitalize recent progresses advanced magnetic resonance imaging mri protocols objective presented crosssectional study evaluated utility four different mri relaxation metrics diffusionweighted imaging ppms methods conventional free precession t1 t2 rotating frame adiabatic t1 t2 combination diffusionweighted parameters acquired 13 ppms patients 13 age sexmatched controls results t1 marker crucial relevance ppms due sensitivity neuronal loss revealed largescale changes mesiotemporal structures sensorimotor cortex cingulate combination diffuse alterations white matter cerebellum t2 particularly sensitive local tissue background gradients thus indicator iron accumulation concurred similar topography damage lower extent moreover adiabatic protocols outperformed conventional t1 t2 maps diffusion tensor kurtosis approaches methods previously used mri research ppms conclusion study introduces adiabatic t1 t2 elegant markers confirming largescale cortical gray matter cerebellar white matter alterations ppms invisible vivo biomarkerspmid34594184 pmcpmc8476998 doi103389 fnins2021711067,0.0
risk dementia apoe 4 carriers mitigated polygenic risk score alzheimers dement amst 2021 sep 14 13 1 e12229 doi 101002 dad212229 ecollection 2021abstractintroduction investigated relationships among genetic determinants alzheimers disease ad amyloid tau neurodegenaration atn biomarkers risk dementiamethods studied cognitively normal individuals subjective cognitive decline scd amsterdam dementia cohort science project examined associations genetic variants atn biomarkers evaluated predictive value incident dementia polygenic risk score prs calculated based 39 genetic variants apoe gene included prs analyzed separatelyresults prs apoe 4 associated amyloidpositive atn profiles apoe 4 additionally isolated increased tau at+n high prs apoe 4 separately predicted ad dementia combined high prs increased low prs attenuated risk associated 4 carriersdiscussion genetic variants beyond apoe clinically relevant contribute pathophysiology ad future prs might used individualized risk profilingpmid34541285 pmcpmc8438688 doi101002 dad212229,0.0
candida tropicalis systemic infection redirects leukocyte infiltration kidneys attenuating encephalomyelitis j fungi basel 2021 sep 14 7 9 757 doi 103390 jof7090757abstractenvironmental factors including infections strongly associated pathogenesis multiple sclerosis ms autoimmune demyelinating disease central nervous system cns although classically associated bacterial viral agents fungal species also suspected affect course disease candida tropicalis opportunistic fungus affects immunocompromised individuals also able spread vital organs c tropicalis increasingly isolated systemic infections aimed evaluate effect fungus experimental autoimmune encephalomyelitis eae murine model study ms eae induced female c57bl 6 mice 3 days infection 106 viable c tropicalis yeasts infection decreased eae prevalence severity confirmed less inflammatory infiltrate less demyelization lumbar spinal cord despite c tropicalis infection associated eae results death animals increased urea creatinine serum levels kidneys eaeinfected mice showed higher fungal load associated increased leukocyte infiltration cd45+ cells higher expression tbox transcription factor tbx21 forkhead box p3 foxp3 altogether results demonstrate although c tropicalis infection reduces prevalence severity eae partially due sequestration leukocytes inflamed renal tissue effect associated poor disease outcomepmid34575795 doi103390 jof7090757,1.0
can improve patients access new drugs uncertainties south koreas experience risk sharing arrangements background new drugs including cancer drugs orphan drugs becoming increasingly expensive risk sharing arrangements rsas manage risk based financial impact health outcome new drugs reimbursed improve patients access new drugs uncertainties many developed countries adopted rsas study aimed understand effects rsas south korea patients accessmethodswe reviewed current status rsa drugs south korea number appraisals time gap market approval reimbursement per rsa drug considered quantify improvement patients access showed rapidly decisions reimbursement rsa drugs derived applied comparative analysis determine whether rsa drugs south korea reimbursed uk italy australia data study obtained websites governmental department agencies responsible appraisal drug reimbursement country literatures related rsas investigated wellresultsthe eligibility korean rsas two key components drugs cancer rare diseases alternative treatments first half 2019 39 rsa drugs reimbursed south korea majority financialbased schemes refund expenditure cap representative types 897 introduction rsas time gap number appraisals decreased based indications rsa drugs level drug coverage south korea found lower italy similar uk higher australiaconclusionsrsas south korea significantly enhanced patients access new drugs led alleviation patients outofpocket expenses drug coverage south korea level comparable countries study provides implications countries dual mission containing pharmaceutical expenditure improving access new drugs,0.0
detection ataxia low disability ms patients hybrid convolutional neural networks based images plantar pressure distribution abstractbackgroundthis study aimed detect ataxia patients multiple sclerosis pwms deep learningbased approach based images showing plantar pressure distribution patients secondary aim study investigate alternative objective method early diagnosis ataxia patientsmethodsa total 105 images showing plantar pressure distribution 43 ataxic pwms 62 healthy individuals analyzed images resized models including vgg16 vgg19 resnet densenet mobilenet nasnetmobile nasnetlarge feature vectors extracted resized images classified using support vector machines svm knearest neighbors knn artificial neural network ann 10fold crossvalidation applied increase validity classifiersresultsthe vgg19svm hybrid model showed highest accuracy sensitivity specificity values 8923 8965 8888 respectively conclusionthe proposed method provided automatic decision support system detecting ataxia based images showing plantar pressure distribution patients pwms performance proposed method indicated method can applied clinical practice establish rapid diagnosis ataxia asymptomatic difficult detect clinically can recommended useful aid physician clinical practice,0.0
platelet inhibition lowdose acetylsalicylic acid reduces neuroinflammation animal model multiple sclerosis int j mol sci 2021 sep 14 22 18 9915 doi 103390 ijms22189915abstractaside established immunemediated etiology multiple sclerosis ms compelling evidence implicates platelets important players disease pathogenesis specifically numerous studies highlighted activated platelets promote central nervous system cns directed adaptive immune response early disease course platelets therefore present novel opportunity modulating neuroinflammatory process characterizes ms hypothesized wellknown antiplatelet agent acetylsalicylic acid asa inhibit neuroinflammation affecting platelets applied lowdose investigated effect experimental autoimmune encephalomyelitis eae model study ms found oral administration lowdose asa alleviates symptoms eae accompanied reduced inflammatory infiltrates less extensive demyelination remarkably percentage cnsinfiltrated cd4+ t cells major drivers neuroinflammation decreased 4098 328 asatreated mice compared 5611 146 control animals disease maximum revealed flow cytometry interestingly plasma levels thromboxane a2 decreased concentrations platelet factor 4 glycoprotein vi affected lowdose asa treatment overall demonstrate lowdose asa ameliorate plateletdependent neuroinflammatory response vivo thus indicating potential treatment approach mspmid34576080 doi103390 ijms22189915,1.0
dysregulation ribosomerelated genes ankylosing spondylitis systems biology approach experimental method background ankylosing spondylitis autoimmune rheumatic disease candidate gene associations reported current understanding pathogenesis remains still poor thus exact mechanism needed urgently disclosed purpose study identify candidate genes involving diseasemethods resultsgse25101 publicly available microarray gse117769 rnaseq datasets patients obtained bioinformatics analyses gene set enrichment analysis showed microarray dataset ribosome pathway significantly upregulated compared controls furthermore ribosomal components demonstrated overexpression patients rnaseq dataset confirm findings 20 patients 20 matching controls selected rheumatology research center clinic shariati hospital pbmcs separated whole blood rna contents extracted following results datasets analysis expression level rrna58s pseudogene rrna18s pseudogene rpl23 rpl7 rpl17 genes measured realtime pcr findings showed dysregulation rrna58s rrna18s pseudogenes also rpl17 gene patientsconclusionconsidering genes involved ribosome biogenesis contributed asassociated biological processes well diseases comorbidities results might advance understanding pathological mechanisms ankylosing spondylitis,0.0
mutations john cunningham virus vp1 gene predispose development progressive multifocal leukoencephalopathy multiple sclerosis patients undergoing treatment natalizumab abstractbackgroundpatients multiple sclerosis ms undergoing treatment natalizumab ntz risk developing progressive multifocal leukoencephalopathy pml due reactivation john cunningham jc virus relevant characteristic among pml cases development single nucleotide mutations vp1 gene causal jc virus identification mutations timely manner can provide valuable information ms managementobjectiveto identify mutations along jc virus vp1 gene ms patients undergoing treatment ntz correlate antijc virus antibody indexmethodseightyeight ms patients one hundred twenty controls six patients diagnosis human immunodeficiency virus hiv without secondary pml included jc virus identified peripheral blood mononuclear cells cerebrospinal fluid pcr amplification sequencing entire length vp1 gene performed positive clinical samplesresultsin ms cases mutations observed jc virus vp1 gene positive hiv controls pml interestingly jc virus vp1 gene sequence derived hiv patients exhibited nonsilent substitution position 186 gc leading amino acid change lysasp find correlation antijc virus antibody index dna viral detectionconclusions identification single nucleotide mutants jc virus vp1 gene might early predictive marker pml efficient patient treatment followup,0.0
citrullinated#x2f native index autoantibodies hnrnpdl predicts individual window treatment success ra patients background need biomarker identify patients risk rheumatoid arthritis riskra better predict therapeutic response study tested hypothesis novel native citrullinated heterogeneous nuclear ribonucleoprotein hnrnp dl autoantibodies possible biomarkersmethodsusing protein macroarray elisa epitope recognition hnrnpdl analysed sera different developed ra disease diagnosed sle patients tolllike receptor tlr 7 9 myeloid differentiation primary response gene 88 myd88 dependency studied sera murine disease models hnrnpdl expression cultivated cells synovial tissue analysed indirect immunofluorescence immunoblot immunohistochemistryresultshnrnpdl highly expressed stress granules citrullinated rheumatoid joint targeted autoantibodies either native citrullinated proteins patient subsets different developed ra disease structural citrullination dependent epitopes sces hnrnpdl detected 58 sle patients although 98 sera ccp2negative obtain specific citrullinated signal value subtracted native antibody value citrullinated signal citrullinated native index autoantibodies hnrnpdl cndlindex identified new value individual window treatment success early ra detection rf igm ccp2 seronegative ra patients 2446 negative cndlindex found sle patients riskra early ra cohorts eira majority patients das28responders methotrexate mtx treatment 87 high positive cndlvalues associated severe ra shared epitope parenchymal changes lung specifically native hnrnpdl tlr7 9dependent associated pain roc analysis revealed association initial mtx etanercept treatment response especially seronegative ra patientsconclusioncndlindex defines people risk develop ra window treatment success thereby closing sensitivity gap ra,0.0
erratum quot propensitymatched comparison longterm disability worsening patients multiple sclerosis treated dimethyl fumarate fingolimodquot ther adv neurol disord 2021 sep 14 1417562864211044631 doi 101177 17562864211044631 ecollection 2021abstract corrects article doi 101177 17562864211021177 pmid34539815 pmcpmc8445527 doi101177 17562864211044631,0.0
comparison mri lesion evolution different central nervous system demyelinating disorders neurology 2021 jul 14101212 wnl0000000000012467 doi 101212 wnl0000000000012467 online ahead printabstractbackground objective studies compare lesion evolution across different cns demyelinating diseases yet knowledge may important diagnosis understanding differences disease pathogenesis sought compare mri t2lesion evolution myelinoligodendrocyteglycoproteiniggassociated disorder mogad aquaporin4iggpositive neuromyelitis optica spectrum disorder aqp4iggnmosd multiple sclerosis ms methods descriptive study retrospectively identified mayo clinic patients mogad aqp4iggnmosd ms 1 brain myelitis attack 2 available attack mri within 6 weeks 3 followup mri beyond 6 months without interval relapses region two neurologists identified symptomatic largest t2lesion patient index lesion mris independently reviewed two neuroradiologists blinded diagnosis determine resolution t2lesions consensus index t2lesion area manually outlined acutely followup assess variation sizeresults included 156 patients mogad 38 aqp4iggnmosd 51 ms 67 172 attacks brain 81 myelitis 91 age median range differed mogad 25 274 aqp4iggnmosd 53 1078 ms 37 1661 p001 female sex predominated aqp4iggnmosd 41 51 80 ms 51 67 76 groups among mogad 17 38 45 complete resolution index t2lesion frequent mogad brain 13 18 72 spine 22 28 79 aqp4iggnmosd brain 3 21 14 spine 0 34 0 ms brain 7 42 17 spine 0 29 0 p0001 resolution t2lesions occurred often mogad brain 7 18 39 spine 22 28 79 aqp4iggnmosd brain 2 21 10 spine 0 34 0 ms brain 2 42 5 spine 0 29 0 p 001 larger median range reduction t2lesion area mm2 followup axial brain mri mogad 213 55873 aqp4iggnmosd 104 07597 p002 ms 36 0506 p 0001 reductions size sagittal spine mri followup mogad 262 0888 aqp4iggnmosd 309 01885 similar p04 greater ms 23 0152 p0001 conclusions mri t2lesions mogad resolve completely often aqp4iggnmosd ms implications diagnosis monitoring disease activity clinical trial design also providing insight pathogenesis central nervous system demyelinating diseasespmid34261784 doi101212 wnl0000000000012467,1.0
corrigendum quot rituximab versus mitoxantrone comparing effectiveness safety advanced relapsing multiple sclerosisquot ther adv chronic dis 2021 sep 14 1220406223211046076 doi 101177 20406223211046076 ecollection 2021abstract corrects article doi 101177 20406223211024366 pmid34729146 pmcpmc8445523 doi101177 20406223211046076,0.0
intermittent fasting possible benefits obesity diabetes multiple sclerosis systematic review randomized clinical trials nutrients 2021 sep 13 13 9 3179 doi 103390 nu13093179abstractintermittent fasting become popular recent years controversially presented possible therapeutic adjunct bibliographic review literature intermittent fasting obesity diabetes multiple sclerosis carried scientific quality methodology results obtained evaluated pairs intermittent fasting beneficial effects lipid profile associated weight loss modification distribution abdominal fat people obesity type 2 diabetes well improvement control glycemic levels patients multiple sclerosis data available scarce draw firm conclusions appear intermittent fasting may safe feasible intervention however necessary continue investigating longterm effects since far studies carried small short durationpmid34579056 doi103390 nu13093179,0.0
disruption white matter structural network correlation baseline progression rate patients sporadic amyotrophic lateral sclerosis abstractobjectivethere increasing evidence amyotrophic lateral sclerosis als progressive neurodegenerative disease impacting largescale brain networks however still unclear structural networks associated disease whether network connectomics associated disease progression study aimed characterize network abnormalities als identify networkbased biomarkers predict als baseline progression ratemethodsmagnetic resonance imaging performed 73 patients sporadic als 100 healthy participants acquire diffusionweighted magnetic resonance images construct white matter wm networks using tractography methods global regional network properties compared als healthy subjects singlesubject wm network matrices patients used predict als baseline progression rate using machine learning algorithmsresultscompared healthy participants patients als showed significantly decreased clustering coefficient cp p 00034 t 298 normalized clustering coefficient p 0039 t 208 smallworldness p 0038 t 210 global network level patients also showed decreased regional centralities motor nonmotor systems including frontal temporal subcortical regions using singlesubject structural connection matrix classification model distinguish patients fast versus slow progression rate average accuracy 85conclusiondisruption wm structural networks als indicated weaker smallworldness disturbances regions outside motor systems extending classical pathophysiological understanding als motor disorder individual wm structural network matrices als patients potential neuroimaging biomarkers baseline disease progression clinical practice,0.0
nanoscale model system human myelin sheath biomacromolecules 2021 jul 29 doi 101021 acsbiomac1c00714 online ahead printabstractneurodegenerative disorders among common diseases modern society however molecular bases diseases multiple sclerosis charcotmarietooth disease remain far fully understood research field limited complex nature native myelin difficulties obtaining good vitro model systems myelin introduce easytouse model system myelin sheath can used study myelin proteins nativelike yet wellcontrolled environment end present myelinmimicking nanodiscs prepared one amphiphilic copolymers styrene maleic acid sma diisobutylene maleic acid dibma styrene maleimide sulfobetaine smasb nanodiscs tested lipid composition using chromatographic hplc mass spectrometric ms methods utilizing spin probes within nanodisc comparability liposomes studied addition binding behavior bovine myelin basic protein mbp scrutinized ensure nanodiscs represent suitable model system myelin results suggest sma smasb able solubilize myelinlike cytoplasmic liposomes without preferences specific lipid headgroups fatty acyl chains nanodiscs sma smasb called sma sb lipid particles short smalps smasblps respectively polymers restrict lipids motion hydrophobic center bilayer headgroups lipids however sterically less hindered nanodiscs compared liposomes myelinlike smalps able bind bovine mbp can stack lipid bilayers like native myelin showing usability simple wellcontrolled systems studies proteinlipid interactions native myelinpmid34324309 doi101021 acsbiomac1c00714,1.0
restless legs syndrome periodic limb movements 86 patients multiple sclerosis sleep 2021 mar 15zsab066 doi 101093 sleep zsab066 online ahead printabstractstudy objectives assess frequency restless legs syndrome rls periodic limb movements sleep plms overlap large sample patients multiple sclerosis ms compare clinical paraclinical findings among four subgroups patients rls plms patients without rls plms rls+ plms patients rls without plms rls plms patients without rls plms rls+ plms+ patients rls plms methods crosssectional observational instrumental study eightysix patients m f 27 59 mean age 480 108 years diagnosis ms underwent telephone interview assessing five standard diagnostic criteria rls seventysix participants underwent polysomnography psg maintenance wakefulness test instrumental clinical findings subsequently statistically compared investigate association rls plms index plmsi results rls plms plmsi 15 h frequency patients ms 314 316 respectively among patients rls 375 plmsi 15 h rls plms+ group showed higher wake sleep onset p 001 stage shifts per hour p 003 increased stage n1 p 003 reduction stage n3 p 001 compared rls plms rls influence clinical psg parameters p 045 conclusions rls highly frequent patients ms frequency plms comparable general population low percentage patients rls high plmsi together absence correlation rls female gender older age support existence distinct symptomatic form rls mspmid33720378 doi101093 sleep zsab066,0.0
editorial b cells inflammatory neurodegenerative diseases central nervous system front neurol 2021 sep 13 12759712 doi 103389 fneur2021759712 ecollection 2021no abstractpmid34589053 pmcpmc8473734 doi103389 fneur2021759712,0.0
cooperation host immunity gut bacteria essential helminthevoked suppression colitis background studies inhibition inflammation infection helminth parasites recently overlooked key determinant health gut microbiota infection helminths evokes changes composition hosts microbiota one outcome altered metabolome eg levels shortchain fatty acids scfas gut lumen functional implications helminthevoked changes enteric microbiome composition metabolites poorly understood explored respect controlling enteric inflammationmethodsantibiotictreated wildtype germfree gf free fattyacid receptor2 ffar2 deficient mice infected tapeworm hymenolepis diminuta challenged dnbscolitis disease severity gut expression il10 receptor scfa receptors transporters assessed 3 days later gut bacteria composition assessed 16 s rrna sequencing scfas measured studies assessed ability feces bacteriafree fecal filtrate h diminutainfected mice inhibit colitisresultsprotection disease infection h diminuta abrogated antibiotic treatment observed gfmice bacterial community profiling revealed increase variants belonging families lachnospiraceae clostridium cluster xiva mice 8 days postinfection h diminuta transfer feces mice suppressed dnbscolitis gfmice mice treated bacteriafree filtrate feces h diminutainfected mice protected dnbscolitis metabolomic analysis revealed increased acetate butyrate can reduce colitis feces h diminutainfected mice antibiotictreated h diminutainfected mice h diminutainduced protection dnbscolitis observed ffar2 mice immunologically antiil10 antibodies inhibited anticolitic effect h diminutainfection analyses epithelial cell lines colonoids colon segments uncovered reciprocity butyrate il10 induction il10receptor butyrate transportersconclusionhaving defined feedforward signaling loop il10 butyrate following infection h diminuta study identifies gut microbiome critical component anticolitic effect helminth therapy suggest intentiontotreat helminth therapy based characterization patients immunological microbiological response helminth,0.0
importance tcell response covid19 vaccination patients multiple sclerosis treated anticd20 therapies new vaccines required developed eagerly read iannetta et als article tcell response sarscov2 patients multiple sclerosis ms treated ocrelizumab iannetta et al 2021 jul 21 article indicated despite sharp decrease b lymphocyte counts patients cd4 + cd8 + tcell absolute relative counts normal five patients finding explain conflicting evidence effect kinds drugs anticd 20 therapies incidence mortality ms patients infected covid19 although number studies reported increase covidinduced deaths ms patients treated rituximab caldernparra et al 2021 aug 12 studies reported increase incidence sahraian et al 2020 nov others lack effect drugs incidence hospitalization death patients covid19 reported monteroescribano et al 2020 iannetta et als article can describe contradiction fact true antibodies patients may produced produced small quantities appropriate response t cells can reason good prognosis covid19 high percentage patients consuming drugs similar concern immune response patients covid19 vaccine studies published reducing vaccination response patients louapre et al 2021 aug 2 however important point studies examined amount antibodies produced patients vaccination knowledge one study examined response t cells vaccination patients receiving immunosuppressive drugs showed despite reduced humoral response tcell response appropriate patients prendecki et al 2021 aug 6 study development covid19 patients taking drugs vaccination however seems due appropriate tcell response despite reduced humoral response incidence covid19 development ms patients significantly reduced vaccination hence claim requires studiesthe next issue future development anticovid vaccines based findings know vaccines stimulate humoral cellular immune systems ewer et al 2021 feb moreover studies showed cellular response occurs much faster kalimuddin et al 2021 jun 11 furthermore observed cellular response greater importance recipients drugs therefore may necessary develop vaccines stimulate cellular response immune system thereby helping prevent covid19 patients receiving anticd 20 therapies,0.0
graves#39 disease spontaneous resolution following ocrelizumab primary progressive multiple sclerosis endocr regul 2021 sep 13 55 3 169173 doi 102478 enr20210018abstractobjectives immune reconstitution therapies irt include antibodybased celldepleting therapies targeting cd52+ alemtuzumab cd20+ rituximab ocrelizumab leukocytes approved treatment multiple sclerosis thyroid autoimmunity common adverse effect alemtuzumab treatment graves disease gd prevalent manifestation date thyroid autoimmunity events reported cd20targeting monoclonal antibodies case report 59yearold woman primary progressive multiple sclerosis prior personal history thyroid disease autoimmunity diagnosed gd 6 months following first ocrelizumab infusion asymptomatic signs ophthalmopathy due temporal association gd diagnosis ocrelizumab infusion absence symptoms experience alemtuzumabinduced gd decided active surveillance strategy antithyroid drugs started underwent spontaneous resolution hyperthyroidism thyroidstimulating hormone tsh receptor antibodies trab negativity mild transitory period subclinical hypothyroidism continued biannually ocrelizumab administration schedule present date maintained close clinical biochemical surveillance normal tsh free thyroxine ft4 free triiodothyronine ft3 levels undetectable trab conclusions first case gd reported ocrelizumab administration timing onset course case similar alemtuzumabinduced gd usually interpreted immune reconstitution syndrome however ocrelizumab cell count depletion inferior severity cell population affected duration depletion case highlights importance prescreening followup thyroid function tests patients treated ocrelizumab novel therapeutic antibody investigation required unravel causes thyroid autoimmunitypmid34523298 doi102478 enr20210018,0.0
alternative activation macrophages interleukin13loaded extralargepore mesoporous silica nanoparticles suppresses experimental autoimmune encephalomyelitis acs biomater sci eng 2021 aug 26 doi 101021 acsbiomaterials1c00946 online ahead printabstractmultiple sclerosis ms treatment via cytokinemediated immunomodulation hampered difficulty cytokines can stably noninvasively delivered central nervous system show interleukin il 13 packaged extralargepore mesoporous silica nanoparticles xlmsns protected degradation directs alternative activation macrophages vitro vivo furthermore noninvasive intranasal delivery il13loaded xlmsns ameliorated symptoms experimental autoimmune encephalomyelitis murine model ms accompanied induction chemokines orchestrating immune cell infiltration results demonstrate therapeutic potential il13loaded xlmsns ms patientspmid34435775 doi101021 acsbiomaterials1c00946,0.0
multiple sclerosis recognition biorthogonal wavelet features fitnessscaled adaptive genetic algorithm front neurosci 2021 sep 13 15737785 doi 103389 fnins2021737785 ecollection 2021abstractaim multiple sclerosis ms disease can affect brain spinal cord leading wide range potential symptoms method aims propose novel ms recognition method methods first bior44 wavelet used extract multiscale coefficients second three types biorthogonal wavelet features proposed calculated third fitnessscaled adaptive genetic algorithm faga combination standard genetic algorithm adaptive mechanism powerrank fitness scalingis harnessed optimization algorithm fourth multipleway data augmentation utilized training set setting 10 runs 10fold crossvalidation method abbreviated bwffaga results method achieves sensitivity 9800 095 specificity 9778 095 accuracy 9789 094 area curve method 09876 conclusion results show proposed bwffaga method better 10 stateoftheart ms recognition methods including eight artificial intelligencebased methods two deep learningbased methodspmid34588953 pmcpmc8473924 doi103389 fnins2021737785,0.0
pacs1neurodevelopmental disorder clinical features trial readiness background pacs1neurodevelopmental disorder pacs1ndd ultrarare condition due recurrent mutation pacs1 gene little systematically collected data exist functional abilities neurodevelopmental morbidities children pacs1nddmethodsparents individuals pacs1ndd completed online survey designed collaboratively researchers parents clinicians analyses focused confirmed r203w variantresultsof 35 individuals confirmed variants 18 51 female median age 8 years interquartile range 4515 seventeen 49 diagnosis epilepsy twelve 40 30 responding question reported autism n 11 30 37 reported features autism children walked independently n 29 32 91 pincer grasp n 23 32 72 feed independently n 15 32 47 used speech n 23 32 72 sixteen twentynine 55 simple preacademic skills neither epilepsy autism associated functional abilities clinical features p 005 conclusionspacs1ndd moderatelysevere intellectual disability syndrome seizures occur defining primary feature successful precision medicine clinical trials ultrarare disorder must target important core features disorder utilize assessment tools commensurate level function clinical population,0.0
acting centrally peripherally renewed interest central nervous system penetration diseasemodifying drugs multiple sclerosis abstractwith recent approval cladribine tablets siponimod ozanimod renewed interest extent current generation diseasemodifying therapies dmts able cross central nervous system cns penetration bloodbrain barrier bbb may influence ability treat multiple sclerosis ms integrity cns maintained bbb bloodcerebrospinal fluid barrier arachnoid barrier play important role preserving immunological environment homeostasis within cns integrity bbb decreases course ms putative temporal relationship disease worsening furthermore currently considered progression disease mediated mainly resident cells cnsthe existing literature provides evidence show current generation dmts ms able penetrate cns potentially exert direct effects cnsresident cells particular cnspenetrating prodrugs cladribine fingolimod sphingosine1 phosphate receptor modulators siponimod ozanimod current generation dmts appear restricted periphery due high molecular weight physicochemical propertiesas effective brain penetrant therapies developed treatment ms need understand whether potential direct effects within cns significance whether brings additional benefits treatment effects mediated periphery turn will require improved understanding structure function bbb role plays ms subsequent treatmentsthis narrative review summarizes data supporting biological plausibility potential benefit therapeutic molecules entering cns discusses potential significance current future treatment ms,1.0
venous pressure theory multiple sclerosis pathophysiology deserve second chance summarythe theory multiple sclerosis related venous pressure discredited due previous operator dependent diagnostic criteria premature attempts treatment 1 elevation venous pressure may component compliance changes found ms 2 neck veins may supply component venous pressure elevation found intracranially although targeted approach towards neck angioplasty towards disease subtype favorable stenoses may beneficial advocate caution encourage others give venous pressure theory second chance replicate work,0.0
follicular helper cd4 + t cells follicular regulatory cd4 + t cells inducible costimulator roles multiple sclerosis experimental autoimmune encephalomyelitis mediators inflamm 2021 sep 12 20212058964 doi 101155 2021 2058964 ecollection 2021abstractfollicular helper cd4+ t tfh cells specialized subset effector t cells play central role orchestrating adaptive immunity tfh cells mainly promote germinal center gc formation provide help b cells immunoglobulin affinity maturation classswitch recombination b cells facilitate production longlived plasma cells memory b cells tfh cells express nuclear transcriptional repressor b cell lymphoma 6 bcl6 chemokine cxc motif receptor 5 cxcr5 cd28 family members programmed cell death protein1 pd1 inducible costimulator icos also responsible secretion interleukin21 il21 il4 follicular regulatory cd4+ t tfr cells regulatory counterpart tfh cells participate regulation gc reactions tfr cells express markers tfh cells also express markers regulatory t treg cells containing foxp3 glucocorticoidinduced tumor necrosis factor receptor gitr cytotoxic t lymphocyte antigen 4 ctla4 il10 hence owing dual characteristic tfh cells treg cells icos expressed activated cd4+ effector t cells participates t cell activation differentiation effector process expression icos highest tfh tfr cells indicating key regulator humoral immunity multiple sclerosis ms severe autoimmune disease affects central nervous system results disability mediated autoreactive t cells evolving evidence remarkable contribution humoral responses review summarizes recent advances regarding tfh cells tfr cells icos well functional characteristics relation mspmid34552387 pmcpmc8452443 doi101155 2021 2058964,0.0
plasma neurofilament light chain level predicts outcomes stroke patients receiving endovascular thrombectomy background timely endovascular thrombectomy evt significantly improves outcomes patients acute ischemic stroke ais large vessel occlusion type however whether certain central nervous systemspecific plasma biomarkers correlate outcomes unknown evaluated temporal changes prognostic roles levels biomarkers patients ais undergoing evtmethodswe enrolled 60 patients received evt ais 14 controls levels plasma biomarkers namely neurofilament light chain nfl glial fibrillary astrocytic protein gfap tau ubiquitin cterminal hydrolase l1 uchl1 measured ultrasensitive single molecule array immediately 24 h evt t1 t2 t3 respectively outcomes interest death disability 90 days defined modified rankin scale score 36 types hemorrhagic transformation hemorrhagic infarction parenchymal hemorrhage resultsof 180 blood samples 60 patients received evt plasma nfl gfap uchl1 levels t1 significantly higher controls levels four biomarkers significantly higher t3 patients parenchymal hemorrhage significantly higher rate increase gfap pinteraction 0005 uchl1 pinteraction 0007 levels compared without parenchymal hemorrhage multivariable analysis adjustment age sex national institute health stroke scale score history atrial fibrillation recanalization status higher nfl levels t1 odds ratio 205 95 confidence interval ci 103408 t2 208 95 ci 105401 t3 394 95 ci 1441079 independent predictors death disability 90 daysconclusionamong patients ais received evt hemorrhagic transformation exhibited significant increase plasma gfap uchl1 levels time higher plasma nfl predictive unfavorable functional outcomes,0.0
fully hydrogenated canola oil extends lifespan strokeprone spontaneously hypertensive rats background canola oil can several vegetable oils shorten lifespan strokeprone spontaneously hypertensive rats shrsp although similar lifespan shortening reported partially hydrogenated can efficacy fully hydrogenated oils lifespan remains unknown present study aimed investigate lifespan shrsp fed diets containing 10 w w fully hydrogenated can fhco oilsmethodssurvival test upon weaning male shrsp fed basal diet rodents mixed one test oils ie fhco can lard lrd palm oil plm throughout experiment animals freely access diet drinking water water containing 1 nacl body weight food intake lifespan recordedbiochemical analysis test male shrsp fed test diet either fhco can soybean oil soy condition except emphasize effects fat nacl loading applied soy used fat source basal diet set control group blood pressures checked every 2 weeks serum fat levels histological analyses brain kidney examined 7 12 weeks feedingresultsduring survival study period food consumption fhcofed rats significantly increased 1520 w w compared rats fed oil however body weight gain fhco group significantly less 1012 control group 911 weeks old fhco 180 days intervention greatest effect lifespan followed lrd 115 6 days plm 101 2 days can 94 3 days diets fhco remarkably decreased serum cholesterol level compared can systolic blood pressure 12 16 weeks age addition rats can group exhibited brain hemorrhaging renal dysfunction 16 weeks old symptoms observed fhco groupconclusionthis current study suggests complete hydrogenation decreases toxicity can even prolongs lifespan shrsp,0.0
lncrna hoxaas2 regulates microglial polarization via recruitment prc2 epigenetic modification pgc1 expression background microgliamediated neuroinflammation plays important role parkinsons disease pd exerts proinflammatory antiinflammatory effects depending m1 m2 polarization phenotype hence promoting microglia toward antiinflammatory m2 phenotype potential therapeutic approach pd long noncoding rnas lncrnas crucial progression neurodegenerative diseases little known role microglial polarization pdmethodsin study profiled expression lncrnas peripheral blood mononuclear cells pbmcs pd patients using microarray rtqpcr used evaluate lncrna levels mrna levels cytokines microglial cell markers vitro vivo rip chip assays analyzed underlying mechanism lncrna regulating microglial polarizationresultswe found hoxaas2 upregulated pbmcs pd patients negatively associated peroxisome proliferatoractivated receptor gamma coactivator1a pgc1 expression moreover hoxaas2 knockdown significantly repressed microglial m1 polarization promoted m2 polarization regulating pgc1 expression mechanistic investigations demonstrated hoxaas2 directly interact polycomb repressive complex 2 prc2 modulate histone methylation promoter pgc1conclusionsour findings identify upregulated lncrna hoxaas2 promotes neuroinflammation regulating microglial polarization interacts prc2 complex epigenetically silencing pgc1 hoxaas2 may potential therapeutic target microgliamediated neuroinflammation patients pd,0.0
sequencing neurofilament genes identified nefh ser787arg novel risk variant sporadic amyotrophic lateral sclerosis chinese subjects background amyotrophic lateral sclerosis als devastating neurodegenerative disease neuronal cell inclusions composed neurofilaments abnormal aggregative proteins pathological hallmarks approximately 90 patients sporadic cases sals least 4 genes ie c9orf72 sod1 fus tardbp identified main causative genes many others proposed potential risk genes however mutations explain 10 sals cases neurofilament polypeptides encoded nefh nefm nefl promising protein biomarkers als degenerative diseases however whether genetic variants genes associated als remain ambiguousmethodshere used pcrsanger sequence exons three genes cohort 371 sals patients 711 healthy controls phase validated risk variant another 300 sals patients 1076 controls phase ii resultsa total 92 variants identified including 36 rare heterozygous variants nefh 27 nefm 16 nefl rs568759161 pser787arg nefh reached nominal statistical power p 002 phase p 0009 phase ii casecontrol comparison together phase ii studies showed significantly higher frequency variant cases 9 1342 067 controls 2 3574 007 1206 95 ci 2605588 p 00003 variants passed multiple testing discovery cohort rs568759161 associated als replication cohortconclusionsour results confirmed nefh ser787arg novel sals risk variant chinese subjects nefm nefl associated sals data may implications genetic counselling understanding pathogenesis sals,0.0
eculizumab monotherapy nmosd data prevent openlabel extension abstractduring prevent phase 3 randomized doubleblind placebocontrolled timetoevent study openlabel extension interim analysis 33 adults aquaporin4 immunoglobulin gpositive neuromyelitis optica spectrum disorder aqp4igg + nmosd received eculizumab monotherapy median 28 years range 14 weeks52 years 192 weeks 4 years 96 patients free adjudicated relapses kaplanmeier analysis 95 confidence interval 757994 prevent 95 20 21 patients receiving eculizumab monotherapy disability worsening eculizumab monotherapy provides effective longterm relapse prevention relieving chronic immunosuppression burden patients aqp4igg + nmosd clinicaltrialsgov prevent nct01892345 openlabel extension nct02003144,0.0
gut microbiotamodulated metabolomic profiling shapes etiology pathogenesis autoimmune diseases microorganisms 2021 sep 10 9 9 1930 doi 103390 microorganisms9091930abstractautoimmunity complex multifaceted process contributes widespread functional decline affects multiple organs tissues pandemic autoimmune diseases global health concern augments prevalence incidence autoimmune diseases including type 1 diabetes multiple sclerosis rheumatoid arthritis development autoimmune diseases phenotypically associated gut microbiotamodulated features molecular cellular levels etiology pathogenesis autoimmune diseases comprise alterations immune systems innate adaptive immune cell infiltration specific organs augmented production proinflammatory cytokines stimulated commensal microbiota however relative importance mechanistic interrelationships gut microbial community immune system progression autoimmune diseases still well understood review describe studies profiling gut microbial signatures modulation immunological homeostasis multiple inflammatory diseases elucidate critical roles etiology pathogenesis autoimmune diseases discuss implications findings disorders targeting intestinal microbiome metabolomic associations phenotype autoimmunity will enable progress developing new therapeutic strategies counteract microorganismrelated immune dysfunction autoimmune diseasespmid34576825 doi103390 microorganisms9091930,0.0
palmitoylethanolamide sleep disturbance doubleblind randomised placebocontrolled interventional study background sleep essential wellbeing yet sleep disturbance common problem linked wide range health conditions palmitoylethanolamide pea endogenous fatty acid amide proposed promote better sleep via potential interaction endocannabinoid systemmethodsthis doubleblind randomised study 103 adults compared efficacy tolerability 8 weeks daily supplemented pea formulation 350 mg levagen + placebo sleep quality quantity measured using wrist actigraphy sleep diary questionnairesresultsat week 8 pea supplementation reduced sleep onset latency time feel completely awake improved cognition waking 8 weeks groups improved sleep quality quantity scores similarly difference groups baseline week 8 sleep quantity quality measured actigraphy sleep diariesconclusionthese findings support pea potential sleeping aid capable reducing sleep onset time improving cognition wakingtrial registrationaustralian new zealand clinical trials registry actrn12618001339246 registered 9th august 2018,0.0
risk factors peripartum depression women multiple sclerosis abstractbackgroundperipartum depression ppd underexplored multiple sclerosis ms objectiveto evaluate prevalence risk factors ppd women msmethodsretrospective singlecenter analysis women ms live birth prevalence ppd estimated logistic regression generalized estimating equations gee gee evaluated predictors ppd eg age marital status parity prepregnancy depression anxiety antidepressant discontinuation sleep disturbance breastfeeding relapses gadoliniumenhancing lesions disability factors significant univariable analyses included multivariable analysisresultswe identified 143 live births 111 women mean age 331 47 years ppd found 18 143 pregnancies 126 95 ci 73178 factors associated ppd included older age 116 95 ci 103132 1year increase primiparity 402 ci 1141423 prepregnancy depression 370 ci 1271001 sleep disturbance 323 ci 117891 breastfeeding difficulty 358 ci 1271008 maternal age 117 ci 102134 primiparity 810 ci 1384740 prepregnancy depression 389 ci 1041460 remained significant multivariable analyses relapses mri activity disability associated ppdconclusionthe prevalence ppd ms appeared similar general population likely underestimated due lack screening ppd can affect ms selfmanagement offspring development prospective studies needed,0.0
effects intermittent fasting brain cognitive function nutrients 2021 sep 10 13 9 3166 doi 103390 nu13093166abstractthe importance diet gutbrain axis brain health cognitive function increasingly acknowledged dietary interventions tested potential prevent treat brain disorders intermittent fasting abstinence strong limitation calories 12 48 h alternated periods regular food intake shown promising results neurobiological health animal models review article discuss potential benefits cognitive function possible effects prevention progress brainrelated disorders animals humans summarizing effects metabolic cellular circadian mechanisms lead anatomical functional changes brain review shows clear evidence positive shortterm effect cognition healthy subjects clinical studies show benefits epilepsy alzheimers disease multiple sclerosis disease symptoms progress findings animal studies show mechanisms parkinsons disease ischemic stroke autism spectrum disorder mood anxiety disorders benefit future research disentangle whether positive effects hold true regardless age presence obesity moreover variations fasting patterns total caloric intake intake specific nutrients may relevant components success longitudinal studies randomized clinical trials rcts will provide window longterm effects development progress brainrelated diseasespmid34579042 doi103390 nu13093166,0.0
dementia forensic setting diagnoses obtained using condensed protocol office chief medical examiner new york city j neuropathol exp neurol 2021 aug 13nlab059 doi 101093 jnen nlab059 online ahead printabstractindividuals dementia may come forensic autopsy partly nonnatural deaths eg fallrelated concerns abuse neglect new york city office chief medical examiner nyc ocme brains cases submitted neurodegenerative disease nd workup seventyeight sequential cases evaluated using recently published condensed protocol niaaa guidelines neuropathologic assessment alzheimer disease ad costcutting innovation diagnostic neuropathology nd identified 74 949 brains common ad n 41 525 primary agerelated tauopathy n 26 333 lewy body disease lbd n 25 321 others included agerelated tau astrogliopathy hippocampal sclerosis aging progressive supranuclear palsy multiple system atrophy amyotrophic lateral sclerosis argyrophilic grain disease creutzfeldtjakob disease 268 ad cases involved nonnatural dementiarelated death versus 400 lbd finally 70 897 cases chronic cerebrovascular disease 53 679 moderatetosevere present diverse distribution nds notable high rate diagnoses associated falls eg lbd potential difference hospital neuropathology experience also report high burden cerebrovascular disease demented individuals seen nyc ocme finally demonstrate aforementioned condensed protocol applicable variety nd diagnosespmid34388235 doi101093 jnen nlab059,0.0
assessing diagnosis disclosure concealment multiple sclerosis development initial validation discoms survey abstractbackgroundindividuals multiple sclerosis ms regularly report making strategic decisions whether share diagnosis keep secret many represents key stressor surprisingly impact disclosure concealment understudied ms formal measurement instrument lacking developed diagnosis disclosure concealment ms discoms survey selfassessment tool evaluating 1 frequency concealment behaviors 2 expected consequences diagnosis disclosure persons msmethodsa systematic mixedmethods process used design initial validation discoms associations discoms responses demographics clinical variables mood examined 204 participants msresultsthe 39item discoms shows good psychometric characteristics approximately 25 respondents conceal diagnosis particularly professional settings higher concealment behaviors associated younger age shorter disease duration lower physical disability nearly 50 respondents believed talking openly diagnosis might undesirable professional interpersonal consequences younger age higher depression higher anxiety associated greater expectations negative consequencesconclusiondevelopment validation discoms presents first step toward systematic study impact disco people ms,0.0
teriflunomide inhibits jcpyv infection spread glial cells choroid plexus epithelial cells int j mol sci 2021 sep 10 22 18 9809 doi 103390 ijms22189809abstractseveral classes immunomodulators used treating relapsingremitting multiple sclerosis rrms diseasemodifying therapies except teriflunomide carry risk progressive multifocal leukoencephalopathy pml severely debilitating often fatal virusinduced demyelinating disease teriflunomide shown antiviral activity dna viruses investigated whether treatment cells teriflunomide inhibits infection spread jc polyomavirus jcpyv causative agent pml treatment choroid plexus epithelial cells astrocytes teriflunomide reduced jcpyv infection spread also used droplet digital pcr quantify jcpyv dna associated extracellular vesicles isolated rrms patients detected jcpyv dna patients confirmed pml diagnosis n 2 six natalizumabtreated n 12 two teriflunomidetreated n 7 two nonimmunomodulated n 2 patients 21 patients 12 57 detectable jcpyv either plasma serum csf uniformly negative jcpyv isolation extracellular vesicles increase level detection jcpyv dna versus bulk unprocessed biofluid overall study demonstrated effect teriflunomide inhibiting jcpyv infection spread glial choroid plexus epithelial cells larger studies using patient samples needed correlate vitro findings patient datapmid34575975 doi103390 ijms22189809,1.0
twostage prediction model heterogeneous effects treatments stat med 2021 may 27 doi 101002 sim9034 online ahead printabstracttreatment effects vary across different patients estimation variability essential clinical decisionmaking aimed develop model estimating benefit alternative treatment options individual patients extending risk modeling approach network metaanalysis framework propose twostage prediction model heterogeneous treatment effects combining prognosis research network metaanalysis methods individual patient data available first stage prognostic model predict baseline risk outcome second stage use baseline risk score first stage single prognostic factor effect modifier network metaregression model apply approach network metaanalysis three randomized clinical trials comparing relapses natalizumab glatiramer acetate dimethyl fumarate including 3590 patients diagnosed relapsingremitting multiple sclerosis find baseline risk score modifies relative absolute treatment effects several patient characteristics age disability status impact baseline risk relapse turn moderates benefit expected treatments highrisk patients treatment minimizes risk relapse 2 years natalizumab whereas dimethyl fumarate might better option lowrisk patients approach can easily extended outcomes interest potential inform personalized treatment approachpmid34048066 doi101002 sim9034,0.0
mri demographic clinical characteristics differ familial sporadic ms cases abstractbackgroundmultiple sclerosis ms chronic immunemediated demyelinating disease prevalence incidence ms iran high rising time study conducted compare demographic clinical features mri findings ms patients history disease firstdegree family members fms sporadic ms patients sms determine importance genetic nongenetic factors development disease effect diagnostic therapeutic modalitiesmethodsamong 185 patients admitted study 62 fms patients 123 sms patients patients underwent clinical examination data gathered age sex age onset symptoms number attacks disease course family history diseasemodifying drugs accompanying diseases well mri findings edss scoresresultsin study demonstrated frequency plaques periventricular area significantly higher sms patients 9756 vs 8871 p001 callosal plaques common fms patients 629 vs 4797 p005 statistically borderline nonsignificant evaluated parameters significant difference observedconclusionin study significant difference observed demographic clinical characteristics fms sms patients significant difference two groups mri findings,1.0
whole exome sequencing identifies two novel mutations patient uc associated psc ssa can j gastroenterol hepatol 2021 sep 10 20219936932 doi 101155 2021 9936932 ecollection 2021abstractbackground patients diagnosed ulcerative colitis uc associated primary sclerosis cholangitis psc sessile serrated adenoma ssa rare present study aimed identify potential causative gene mutation patient uc associated psc ssamethods dna extracted blood sample tissue sample ssa followed whole exome sequencing wes analysis bioinformatics analysis utilized predict deleteriousness identified variants multiple sequence alignment conserved protein domain analyses performed using online software sanger sequencing used validate identified variants expression diagnostic analysis identified mutated genes performed gse119600 dataset peripheral blood samples psc uc gse43841 dataset tumor samples ssa results present study total 842 single nucleotide variants snvs 728 genes identified blood sample two variants integrin beta 4 itgb4 cc2503g pp835a mucin 3a muc3a cc1019t pp340l analyzed muc3a associated inflammatory bowel disease sanger sequence blood revealed itgb4 mutation fully cosegregated result wes patient additionally variant tumor protein p53 gene tp53 c86dela pn29tfs 15 identified tissue sample ssa compared normal controls itgb4 upregulated uc psc muc3a respectively upregulated downregulated psc uc tp53 downregulated ssa itgb4 tp53 potential diagnostic value uc psc ssaconclusions present study demonstrated itgb4 cc2503g pp835a muc3a cc1019t pp340l mutations may potential causative variants patient uc associated psc ssa tp53 c86dela pn29tfs 15 mutation may associated ssa patientpmid34545326 pmcpmc8449715 doi101155 2021 9936932,0.0
benchmarks meaningful improvement neurocognitive tests multiple sclerosis abstractbackgroundprevious studies established benchmarks clinically meaningful decline neuropsychological tests however little known meaningful testing benchmarks based gains functionobjectiveinvestigate neuropsychological changes multiple sclerosis ms patients work gains calculate benchmarks meaningful improvement neuropsychological testsmethodsa total 323 people ms monitored longitudinally neuropsychological testing buffalo vocational monitoring surveyresults conclusionsthose work gains showed significant improvement 3 points symbol digit modalities test sdmt time p 001 benchmarks clinically meaningful improvement sdmt similar previously established clinically meaningful decline,0.0
age disease onset associates oxidative stress neuroinflammation impaired synaptic plasticity relapsingremitting multiple sclerosis front aging neurosci 2021 sep 10 13694651 doi 103389 fnagi2021694651 ecollection 2021abstractage onset main risk factor disease progression patients relapsingremitting multiple sclerosis rrms crosssectional study explored whether older age associated specific disease features involved progression independent relapse activity pira 266 patients rrms associations age onset clinical characteristics cerebrospinal fluid csf levels lactate several inflammatory molecules analyzed longterm potentiation ltp like plasticity studied using transcranial magnetic stimulation tms older age associated reduced prevalence clinical radiological focal inflammatory disease activity older patients showed also increased csf levels lactate proinflammatory molecules monocyte chemoattractant protein 1 mcp1 ccl2 macrophage inflammatory protein 1alpha mip1 ccl3 interleukin il 8 finally tms evidenced negative correlation age ltplike plasticity newly diagnosed rrms older age onset associated reduced acute disease activity increased oxidative stress enhanced central inflammation altered synaptic plasticity independently age patients multiple sclerosis ms showing similar clinical immunological neurophysiological characteristics may represent ideal candidates early treatments effective pirapmid34566620 pmcpmc8461180 doi103389 fnagi2021694651,0.0
nuclei isolation superresolution structured illumination microscopy examining nucleoporin alterations human neurodegeneration j vis exp 2021 sep 10 175 doi 103791 62789abstractthe nuclear pore complex npc complex macromolecular structure comprised multiple copies 30 different nucleoporin proteins nups collectively nups function regulate genome organization gene expression nucleocytoplasmic transport nct recently defects nct alterations specific nups identified early prominent pathologies multiple neurodegenerative diseases including amyotrophic lateral sclerosis als alzheimers disease ad frontotemporal dementia ftd huntingtons disease hd advances light electron microscopy allow thorough examination subcellular structures including npc nup constituents increased precision resolution commonly used techniques superresolution structured illumination microscopy sim affords unparalleled opportunity study localization expression individual nups using conventional antibodybased labeling strategies isolation nuclei prior sim enables visualization individual nup proteins within npc nucleoplasm fully accurately reconstructed 3d space protocol describes procedure nuclei isolation sim evaluate nup expression distribution human ipscderived cns cells postmortem tissuespmid34570098 doi103791 62789,0.0
mri patterns distinguish aqp4 antibody positive neuromyelitis optica spectrum disorder multiple sclerosis front neurol 2021 sep 9 12722237 doi 103389 fneur2021722237 ecollection 2021abstractneuromyelitis optica spectrum disorder nmosd multiple sclerosis ms inflammatory diseases cns overlap clinical mri features nmosd ms means distinguishing conditions can difficult aim evaluating diagnostic utility mri features distinguishing nmosd ms conducted crosssectional analysis imaging data developed predictive models distinguish two conditions nmosd ms mri lesions identified defined literature search aquaporin4 aqp4 antibody positive nmosd cases age sexmatched ms cases collected mri orbits brain spine reported least two blinded reviewers mri brain spine available 166 168 99 cases longitudinally extensive 203 bright spotty 938 whole axial 578 gadolinium gd enhancing 286 spinal cord lesions bilateral 313 gdenhancing 154 optic nerve lesions nucleus tractus solitarius 192 periaqueductal 168 hypothalamic 72 brain lesions associated nmosd ovoid 0029 dawsons fingers 0031 pyramidal corpus callosum 0058 periventricular 0136 temporal lobe 0137 t1 black holes 0154 brain lesions associated ms scorebased algorithm decision tree determined machine learning accurately predicted 85 diagnoses using first available imaging alone confirmed nmosd ms specific mri features combined predictive models can accurately identify 85 cases either aqp4 seropositive nmosd mspmid34566866 pmcpmc8458658 doi103389 fneur2021722237,0.0
reduced quality life pediatriconset neuromyelitis optica spectrum disorders cohort abstractbackgroundneuromyelitis optica spectrum disorders nmosd severe condition associated high disability low quality life qol adults since evaluation rarely perfomed children study aimed describe qol pediatriconset nmosd positive aquaporin4 antibody aqp4igg patientsmethodsthis crosssection evaluation patients parentsnull proxy qol individuals enrolled longitudinal cohort aqp4igg positive nmosd onset 18 years ageresultseighteen patients included sixteen girls mean sd age disease onset 115 36 years eleven patients experienced disability mean sd 83 53 years followup nmosd impact qol 10 patients associated higher edss poor academic performance last followup results pedsql inventory 13 patients 10 parents disclosed low qol specially emotional functioningconclusionthis study indicates impaired quality life high disability high impact disease daily life adolescents young adults pediatric onset nmosd,0.0
anxiety depression schoolage patients spinal muscular atrophy crosssectional study background spinal muscular atrophy sma rare neurogenetic disease involves multisystem dysfunctions respiratory digestive motor disorders anxiety depression psychological disorders often accompany severe chronic physical diseases aim study investigate prevalence anxiety depression along influencing factors among schoolage patients smamethodswe conducted crosssectional study schoolage sma patients china patients aged 818 years genetic diagnosis 5qsma invited answer questionnaire composed sociodemographic clinical questions complete screen child anxietyrelated emotional disorders depression selfrating scale depression anxiety level evaluation end questionnaire questions assessed subjective anxiety subjective depression patients caregivers expectations childs futureresultscomplete data available 155 patients sample included 458 boys 542 girls 652 type ii 271 type iii remainder type sma rates anxiety depression schoolage sma patients 400 252 respectively gender age disease type associated anxiety depression respiratory system dysfunction digestive system dysfunction skeletal deformity rehabilitation exercise academic delay specialized support school household income level caregivers subjective anxiety caregivers expectations significantly related anxiety depressionconclusionsthere high prevalence anxiety depression schoolage sma patients china professional psychological care maybe included standard care results also call possible targets intervention reducing complications improving drug accessibility retaining normal schooling strengthening school support enhancing ability caregivers sma patients assist diagnosis treatment disease improving mental health sma patients,0.0
coproduction randomized clinical trials patients case study autologous hematopoietic stem cell transplant patients scleroderma background increasingly argued clinical trials struggle recruit participants respond key questions study treatments patients will willing able use study explores elicitation patientpreferences can help designers randomized controlled trials rcts understand impact changing modifiable aspects treatments trial design recruitmentmethodsfocus groups discrete choice experiment dce survey used elicit preferences people scleroderma autologous hematopoietic stem cell transplant ahsct treatment interventions preferences seven attributes treatment effectiveness immediate longterm risk care team composition experience cost travel distance estimated using mixedlogit model used predict participation rctsresultstwo hundred seventyeight people scleroderma answered survey ahsct treatment attributes significantly influenced preferences treatment effectiveness risk late complications contributed participants choices modifiable factors distance treatment center cost also affected preferences predicted recruitment rates calibrated participation recent trial 33 suggest offering treatment closer home lower patient cost holistic multidisciplinary care increase participation 51conclusionsthrough patient engaged approach preference elicitation different features ahsct treatment options able predict drives decisions people scleroderma participate rcts knowledge regarding concerns tradeoffs people willing make can inform clinical study design improving recruitment rates potential uptake treatment interest,0.0
neural stem cells derived primitive mesenchymal stem cells reversed disease symptoms promoted neurogenesis experimental autoimmune encephalomyelitis mouse model multiple sclerosis background multiple sclerosis ms autoimmune inflammatory disease central nervous system cns ms affects millions people causes great economic societal burden cure ms used novel approach investigate therapeutic potential neural stem cells nscs derived human primitive mesenchymal stem cells mscs experimental autoimmune encephalomyelitis eae mouse model msmethodsmscs differentiated nscs labeled pkh26 injected tail vein eae mice neurobehavioral changes mice assessed effect transplanted cells disease process animals sacrificed two weeks following cell transplantation collect blood lymphatic cns tissues analysis transplanted cells tracked various tissues flow cytometry immune infiltrates determined characterized immunohistochemical staining respectively levels immune regulatory cells treg th17 analyzed flow cytometry myelination determined luxol fast blue staining immunostaining vivo fate transplanted cells expression inflammation astrogliosis myelination neural neuroprotection neurogenesis markers investigated using immunohistochemical qrtpcr analysis resultsmscderived nscs expressed specific neural markers nestin tuj1 vimentin pax6 nscs improved eae symptoms mscs transplanted eae mice posttransplantation analyses also showed homing mscs nscs cns concomitant induction antiinflammatory response resulting reducing immune infiltrates nscs also modulated treg th17 cell levels eae mice comparable healthy controls luxol fast blue staining showed significant improvement myelination treated mice analysis showed nscs upregulated genes involved myelination neuroprotection downregulated inflammatory astrogliosis genes significantly mscs importantly nscs differentiated neural derivatives promoted neurogenesis possibly modulating bdnf fgf signaling pathwaysconclusionsnsc transplantation reversed disease process inducing antiinflammatory response promoting myelination neuroprotection neurogenesis eae disease animals promising results provide basis clinical studies treat ms using nscs derived primitive mscs,1.0
multiple sclerosis prodrome just unspecific symptoms radiologically isolated syndrome patients sufficient evidence dismiss multiple sclerosis ms prodrome unspecific vague symptoms person radiologically isolated syndrome ris unfortunately short answer nothe oxford dictionary defines prodrome early symptom indicating onset disease illness prodromal phases well recognized neurological diseases criteria including clinical markers developed identify individuals prodromal phase1 2 definition prodromal phase may also encompass period disturbance representing deviation persons previous state health eventually leads onset disease contrast ris formally named 2009 defined absence symptoms either neurological suggestive inflammatory demyelinating disease well presence magnetic resonance imaging mri findings corresponding 2005 dissemination space criteria3 thus formal criteria define diagnose ris exist standards prodromal ms4 furthermore recently neither ris prodromal phase ms even thought exist35ris typically identified mri performed reason exploring typical ms symptoms associated central nervous system cns demyelinating disease3 symptoms reported first risdefining mri included migraine headache musculoskeletal pain mood fluctuations3 6 comprehensive historical data individuals ris closely evaluated ensure absence clinical symptomatology suggestive inflammatory demyelinating events proportion individuals fall symptom categories subsequent risk evolution ms remains unknown nonetheless risk factors clinical conversion identified based current evidence motive index mri one them6 however inclusion much larger number study subjects reasons mri overlap identified within ms prodrome may prove otherwise based 2020 study approximately half 51 451 ris participants referred centre specialized ms care united states europe developed ms median 10 years6 younger age cerebrospinal fluid csf profile suggestive cns demyelination presence spinal cord infratentorial lesions index scan independent risk factors clinical conversion 87 risk conversion individuals factors6so ris fit ms prodrome short currently know know formal recognition ris3 predated recent interest ms prodrome4 7 ris prodromal ms likely reflective deficiencies current diagnostic criteria recognition ms general population know individuals developed ms increase healthcare use years leading ms onset suggestive prodromal phase7 reasons increases included mental health issues skinrelated disorders sleep alterations sensory disturbances bladder dysfunction8 9 studies mrirelated findings participants available reasonable hypothesize many also demyelinating lesions cns studies based healthcare utilization also suggest misdiagnoses missed opportunities earlier recognition ms apparent well nonneurological atypical symptoms predating classical ms onset810 thus improved understanding features offers another path towards understanding early events leading onset recognition ms will help optimize diagnostic approaches treatment strategiesthe recognition ris typically chance finding mri scan cranial trauma vehicle accident whether prodromal phase preemptive ms exists individuals ris currently unknown surprising given nascent understanding ms prodrome ris furthermore unknown whether ris ms prodrome continuum represent entirely distinct entities example ris subjects report heat intolerance mood disorders headache paroxysmal symptoms yet present normal neurological examination already prodromal phase ms however relatively nonspecific issues also common general population without ms8 thus unsurprisingly presence one nonspecific features headache migraine found valuable predictors conversion ris ms6 likely combination features factors will needed range clinical signs symptoms demographics eg sex age relevant serum biomarker s family history genetic risk score similar approach used parkinsons disease whereby probability individual prodromal parkinsons disease can estimated research purposes using validated criteria2 research criteria developed ms may also benefit including presence ris study prevalence mri features supportive radiological criteria ms within ms prodromal phase also needed addition need significantly larger numbers subjects ris range mri indications understand symptoms may qualify prodromal impact risk clinical evolution ms worldwide collaboration needed combined efforts may lead development appropriate tools facilitate detection earlier recognition prompt management msconclusionformal recognition ris predates recent interest ms prodrome3 4 thus comes surprise little known ris might overlap ms prodrome sufficient evidence dismiss notion ms prodrome just unspecific symptoms ris patients answer resounding dismissive approach without rigorous study disservice current future patients combined effort needed learning ris emerging field prodromal ms provides opportunity earlier ms detection management possibly even prevention ms future4,1.0
mhealth useful tool selfassessment rehabilitation people multiple sclerosis systematic review brain sci 2021 sep 9 11 9 1187 doi 103390 brainsci11091187abstractthe development mobile technology mobile internet offers new possibilities rehabilitation clinical assessment longitudinal perspective multiple sclerosis management however mobile health applications mhealth developed recently level evidence supporting use mhealth people multiple sclerosis pwms currently unclear therefore review aims list describe different mhealth available rehabilitation selfassessment pwms define level evidence supporting interventions functioning problems categorized within international classification functioning disability health icf total 36 studies performed 22 different mhealth included review 30 rehabilitation six selfassessment representing 3091 patients rehabilitation studies focusing cognitive function fatigue concerning efficacy found small significant effect use mhealth cognitive training standardized mean difference smd 028 012 045 moderate effect fatigue smd 061 047 076 mhealth promising tool pwms studies needed validate solutions icf categories replications studies also needed mhealth assessed one single studypmid34573208 doi103390 brainsci11091187,0.0
csf1rmicroglia axis protective hostspecific roles neurotropic picornavirus infection front immunol 2021 sep 9 12621090 doi 103389 fimmu2021621090 ecollection 2021abstractviral encephalitis major cause morbidity mortality manifestation disease varies greatly individuals even response virus microglia professional antigen presenting cells reside central nervous system cns parenchyma poised respond viral insults however role microglia initiating coordinating antiviral response completely understood utilizing theilers murine encephalomyelitis virus tmev neurotropic picornavirus plx5622 small molecule inhibitor colonystimulating factor 1 receptor csf1r signaling can deplete microglia cns investigated role csf1rmicroglia axis neurotropic picornavirus infection c57bl 6j sjl j mice mouse strains differ ability clear tmev exhibit different neurological disease response tmev infection csf1r antagonism c57bl 6j mice normally clear tmev cns led acute fatal encephalitis contrast csf1r antagonism sjl j mice normally develop chronic cns tmev infection result acute encephalitis exacerbated tmevinduced demyelination immunologically inhibition csf1r c57bl 6j mice reduced major histocompatibility complex ii expression microglia decreased proportion regulatory t cells cns upregulated proinflammatory pathways cns t cells acute csf1r inhibition sjl j mice effect microglial mhcii expression upregulated antiinflammatory pathways cns t cells however chronic csf1r inhibition resulted broad immunosuppression results demonstrate strainspecific effects csf1rmicroglia axis context neurotropic viral infection well inherent differences microglial antigen presentation subsequent t cell crosstalk contribute susceptibility neurotropic picornavirus infectionpmid34566948 pmcpmc8458822 doi103389 fimmu2021621090,1.0
pathologic tau conformer ensembles induce dynamic liquidliquid phase separation events nuclear envelope background microtubuleassociated protein tau forms aggregates different neurodegenerative diseases called tauopathies prior work shown single p301l mutation tau gene mapt can promote alternative tau folding pathways correlate divergent clinical diagnoses using progressive chemical denaturation tau preparations brain featured complex transitions starting low concentrations guanidine hydrochloride gdnhcl denaturant indicating ensemble differently folded tau species called conformers hand brain samples abundant tanglelike pathology simple gdnhcl unfolding profile resembling profile fibrillized recombinant tau suggesting unitary conformer composition studies sought understand tau conformer progression potential relationships condensed liquid states well associated perturbations cell biological processesresultsas starting material used brain samples p301l transgenic mice containing tau conformer ensembles unfolded low gdnhcl concentrations signatures resembling brain material p301l subjects presenting language memory problems seeded reporter cells expressing soluble form 4 microtubulebinding repeat tau fused gfp yfp reporter moieties resulting redistribution dispersed fluorescence signals focal assemblies fuse together move within processes adjacent cells nuclear envelope fluorescent tau signals small fluorescent inclusions behaved demixed liquid phase indicative liquidliquid phase separation llps droplets exhibited spherical morphology fusion events recover photobleaching moreover juxtanuclear tau assemblies associated disrupted nuclear transport reduced cell viability stable cell line staining thioflavin s ths became prevalent tauderived inclusions attained crosssectional area greater 3 m2 indicating bipartite composition ii vivo progression tau conformers iii mass threshold applying demixed condensates may drive liquidsolid transitionsconclusionstau conformer ensembles characterized denaturation low gdnhcl concentration templated production condensed droplets living cells species exhibit dynamic changes develop vivo larger thspositive assemblies may represent waystation arrive intracellular fibrillar tau inclusions seen endstage genetic tauopathies,0.0
multiple sclerosis prodrome just unspecific symptoms radiologically isolated syndrome patients commentary available,0.0
synaptic dysfunction multiple sclerosis red thread inflammation network disconnection int j mol sci 2021 sep 9 22 18 9753 doi 103390 ijms22189753abstractmultiple sclerosis ms clinically considered chronic inflammatory disease white matter however last decade growing evidence supported important role gray matter pathology major contributor msrelated disability involvement synaptic structures assumed key role pathophysiology disease synaptic contacts considered central units information flow involved synaptic transmission plasticity critical processes shaping functioning brain networks course ms immune system diffusible mediators interact synaptic structures leading changes structure function influencing brain network dynamics purpose review provide overview existing literature synaptic involvement experimental human ms order understand mechanisms synaptic failure eventually leads brain networks alterations contributes disabling ms symptoms disease progressionpmid34575917 doi103390 ijms22189753,0.0
multiple sclerosis prodrome just unspecific symptoms radiologically isolated syndrome patients yes abstract available,0.0
optic neuritis asian type opticospinal multiple sclerosis osmson nonasian population functionalstructural paradox abstractbackgroundbiomarkers improved classification autoimmune inflammatory disorders including optic neuritis frequent presentation multiple sclerosis neuromyelitis spectrum disorders mog antibodyrelated disease mogad opticospinal multiple sclerosis osms phenotype osms nonasian populations less well knownobjectivewe investigated clinical features prognosis osmson brazilian cohortmethodsthis singlecenter cohort study patients rio de janeiro brazil osms individuals mog aqp4seronegative clinically diagnosed magnetic resonance imagingconfirmed transverse myelitis tm subjects healthy controls hcs assessed visual acuity logmar va automated perimetry mean deviation md intraocular pressure spectraldomain optical coherence tomography oct followed automated retinal layer segmentation peripapillary retinal nerve fiber layer prnfl macular ganglion cell inner plexiform layer mgcipl receiver operator characteristic curves plotted area curve auc calculated group comparisons retinal asymmetry prnfl mgciplresultsthe 30 patients osms predominantly female white mean age 48 years range 2070 years unilateral index event 833 patients average 18year followup period 89 relapses individuals osms average va 007014 right eye re 013030 left eye le md 537588db 523334db re le respectively significant cumulative loss va p00003 md p00001 higher number recurrent episodes atrophy prnfl thickness significant osms re 78621601m le 79861379m relative hc group re 98871068m le 97871085m p00001 likewise significant mgcipl atrophy patients osms re 74961446m le 73881379m relative hc group re 9050674m le 9041 689m p00001 retinal asymmetry intereye percentage absolute differences accurately separated patients unilateral hcs auc089 auc085 respectively conclusiona structuralfunctional paradox found osms high diagnostic value novel metric based retinal asymmetry functional visual outcome excellent despite significant structural damage inner retinal layers patients high relapse rate longterm bilateral sequential involvement,0.0
functional connectivity prepost exercise intervention individuals relapsingremitting multiple sclerosis neuroreport 2021 jul 19 doi 101097 wnr0000000000001702 online ahead printabstractobjective exercise interventions emerged promising approach managing symptoms associated multiple sclerosis ms however changes brain function underlying exerciserelated improvements symptoms ms fully investigated instances investigated using graph theory approach first time effects exercise intervention functional brain network connectivity examined using graph theory analyses restingstate functional mri fmri data among individuals relapsingremitting ms rrms methods restingstate fmri data obtained 10 participants 12 weeks speeded walking intervention functional connectivity data preprocessed data processing assistant restingstate fmri advanced dparsf version 42 analyzed graphvar202 compute global local graph theory metrics examine differences graph metrics intervention onesample permutation tests performedresults significant pre post exercise intervention changes global metrics changes local metrics ie clustering coefficient local efficiency degree centrality betweenness centrality mixed increases decreases observedconclusion following 12week speeded walking exercise intervention significant increases decreases global graph metrics results level local metrics equivocal individuals rrms research experimental designs include baseline longitudinal followup well larger sample sizes needed understand underlying mechanisms symptom improvement following exercise rrmspmid34284447 doi101097 wnr0000000000001702,0.0
csf chitinase 3like 2 associated longterm disability progression patients progressive multiple sclerosis neurol neuroimmunol neuroinflamm 2021 sep 8 8 6 e1082 doi 101212 nxi0000000000001082 print 2021 novabstractobjective study aimed identify longterm prognostic protein biomarkers associated disease progression patients progressive multiple sclerosis ms methods csf samples collected discovery cohort 28 patients progressive ms participated clinical trial interferon beta patients classified high low disability progression phenotypes according numeric progression rates npr stepbased progression rates spr mean followup time 12 years protein abundance measured shotgun proteomics selected proteins discovery cohort quantified parallel reaction monitoring csf samples independent validation cohort 41 patients progressive ms classified also high low disability progression phenotypes mean followup time 7 yearsresults 2 548 csf proteins identified discovery cohort 10 selected validation based association longterm disability progression spats2like protein chitinase 3like 2 chi3l2 plasma serine protease inhibitor metallothionein3 phospholipase d4 betahexosaminidase neurexophilin1 adipocyte enhancerbinding protein 1 cathepsin l1 lipopolysaccharidebinding protein chi3l2 validated patients high disability progression exhibited significantly higher csf protein levels compared patients low disability progression p 003 npr p 002 spr chi3l2 levels showed good performance discriminate high low disability progression patients progressive ms area curve 073 sensitivity 90 specificity 63 conclusions although confirmatory studies needed propose csf chi3l2 prognostic protein biomarker associated longterm disability progression patients progressive msclassification evidence study provides class ii evidence high csf chi3l2 levels identified higher disability progression patients progressive mspmid34497102 doi101212 nxi0000000000001082,0.0
openlabel randomized multicentre study evaluate anterior controllable antedisplacement fusion versus posterior laminoplasty patients cervical ossification posterior longitudinal ligament study design analysis plan star background treating patients cervical ossification posterior longitudinal ligament copll novel surgery technique anterior controllable antedisplacement fusion acaf suggested promising clinical benefits recent exploratory studiesmethodsthis multicentre randomized openlabel parallelgroup active controlled trial will compare clinical benefits acaf versus conventional posterior laminoplasty lamp severe copll patients total 164 patients will enrolled randomized 11 ratio either acaf lamp group primary efficacy measure cervical japanese orthopaedic association cjoa recovery rate 12 months post operation derived hirabayashis method joa data range 0 worst 17 normal condition important secondary efficacy endpoints include visual analogue scale vas pain score range 0 pain 10 severe 10item neck disability index ndi total range 0 50 points highest index worst 6level nurick disability grade range 0 mild 5 severe safety endpoints including adverse events perioperative complications adverse events special interest will also assessed study full analysis set baseline efficacy data analyses according intentiontotreat principle will established primary analysis population analysis covariance ancova will used analyze cjoa recovery rate random stratification factors appropriate treatment group fixed factors baseline level cjoa score covariatediscussionthis study designed demonstrate clinical benefits acaf compared conventional lamp copll patients will provide clinical evidence novel surgery technique acaf might favorable treating patients severe cervical ossification posterior longitudinal ligament words 290 trial registrationclinicaltrialsgov number nct04968028,0.0
humoral immune response following sarscov2 mrna vaccination concomitant anticd20 therapy multiple sclerosis abstractbackgroundthe immunogenicity covid19 vaccine among patients receiving anticd20 monoclonal antibody ab treatment fully investigated detectable levels sarscov2 immunoglobulin g igg believed predictive value immune protection covid19 currently surrogate indicator vaccine efficacyobjectiveto determine igg abs anticd20 treated patients multiple sclerosis ms methodigg abs sarscov2 spike receptorbinding domain measured sarscov2 igg ii quant assay abbott laboratories vaccination n60 results367 patients mounted positive sarscov2 spike ab response second dose vaccine five patients 83 developed abs 264 bau ml another 12 patients 20 developed intermediate abs 54 bau ml 264 bau ml five patients 83 low levels 54 bau ml seropositive patients 636 converted seronegative seropositive 2nd vaccineconclusionour study demonstrates decreased humoral response bnt162b2 mrna sarscov2 vaccine ms patients receiving bcell depleting therapy clinicians advise patients treated anticd20 avoid exposure sarscov2 future studies investigate implications third booster vaccine patients low absent abs vaccination,0.0
lymphocytemicrogliaastrocyte axis chronic active multiple sclerosis multiple sclerosis ms lesions resolve months form harbour ongoing demyelination axon degeneration identifiable vivo paramagnetic rims mri scans1 2 3 define mechanisms underlying disabling progressive neurodegenerative state4 5 6 foster development new therapeutic agents used mriinformed singlenucleus rna sequencing profile edge demyelinated white matter lesions various stages inflammation uncovered notable glial immune cell diversity especially chronically inflamed lesion edge define microglia inflamed ms mims astrocytes inflamed ms glial phenotypes demonstrate neurodegenerative programming mims transcriptional profile overlaps microglia neurodegenerative diseases suggesting primary secondary neurodegeneration share common mechanisms benefit similar therapeutic approaches identify complement component 1q c1q critical mediator mims activation validated immunohistochemically ms tissue genetically microgliaspecific c1q ablation mice experimental autoimmune encephalomyelitis therapeutically treating chronic experimental autoimmune encephalomyelitis c1q blockade c1q inhibition potential therapeutic avenue address chronic white matter inflammation monitored longitudinal assessment dynamic biomarker paramagnetic rim lesions using advanced mri methods,1.0
gender sex hormone estradiol affect multiple sclerosis risk gene expression epsteinbarr virusinfected b cells front immunol 2021 sep 8 12732694 doi 103389 fimmu2021732694 ecollection 2021abstractmultiple sclerosis ms complex immunemediated disease central nervous system treatment based immunomodulation including specifically targeting b cells b cells main host epsteinbarr virus ebv described necessary ms development 200 genetic loci identified increasing susceptibility ms many ms risk genes altered expression ebv infected b cells dependent risk genotype regulated ebv transcription factor ebna2 females 23 times likely develop ms males investigated ms risk loci might mediate gender imbalance ms large public dataset identified genderspecific associations ebv traits ms risk snp gene pairs gender differences associations gene expression genes also showed gender differences correlation gene expression level estrogen receptor 2 test estrogens may drive gender specific differences cultured ebv infected b cells lymphoblastoid cell lines lcls medium depleted serum remove effects sex hormones well estrogenic effect phenol red supplemented estrogen 100 nm estradiol estradiol treatment altered ms risk gene expression lcl proliferation rate ebv dna copy number ebna2 expression sexdependent manner together data indicate estrogenmediated genderspecific differences ms risk gene expression ebv functions may turn contribute gender differences host response ebv ms susceptibilitypmid34566997 pmcpmc8455923 doi103389 fimmu2021732694,0.0
physical emotional medical socioeconomic status patients nmosd crosssectional survey 123 cases single center north china front neurol 2021 sep 8 12737564 doi 103389 fneur2021737564 ecollection 2021abstractobjective study aimed assess physical emotional medical socioeconomic conditions patients neuromyelitis optica spectrum disorder nmosd north china methods crosssectional survey patients nmosd performed based established questionnaire multiple sclerosis patient survival report 2018 logistic regression analysis conducted define significant determinants certain physical emotional characteristics patients total 123 patients included results total 634 participants initially diagnosed conditions nmosd median delay 6 months accurate diagnosis aggregate 722 patients one relapses corresponding annual relapse rate 08 paresthesia frequent physical symptom among patients disease onset 537 throughout duration disease 862 onset elderly 50 years patients associated annual expanded disability status scale increase 1 compared onset younger 30 years patients p 0001 783 total 764 patients received attackprevention treatments remission phase 317 106 patients ever administered rituximab traditional chinese medicine respectively additionally 634 431 patients reported participating social activities work disease noted 764 patients reported suffering negative emotions frequent worry 602 203 patients experiencing suicidal thoughts inability work participating social activities due nmosd two determinants experiencing negative emotions p work 003 orwork 334 p socialactivities 002 orsocialactivities 319 conclusion study reported patient perspectives nmosd north china whereby demonstrating inability work participating social activities due nmosd rather physical impairment caused disease directly associated patients experiencing negative emotions insight offers potential ways manage patients negative emotions enhancing family social support facilitating active employmentpmid34566879 pmcpmc8455822 doi103389 fneur2021737564,0.0
transgenic fluorescent zebrafish lines revolutionized biomedical research abstractsince debut biomedical research fields 1981 zebrafish used vertebrate model organism 40 000 biomedical research studies especially useful zebrafish lines expressing fluorescent proteins molecule intracellular organelle cell tissue specific manner allow visualization tracking molecules intracellular organelles cells tissues interest real time vivo review summarize representative transgenic fluorescent zebrafish lines revolutionized biomedical research signal transduction craniofacial skeletal system hematopoietic system nervous system urogenital system digestive system intracellular organelles,0.0
prevalence paramagnetic rim lesions multiple sclerosis systematic review metaanalysis plos one 2021 sep 8 16 9 e0256845 doi 101371 journalpone0256845 ecollection 2021abstractbackground recent findings several studies shown paramagnetic rim lesions identified using susceptibilitybased mri represent potential diagnostic prognostic biomarkers multiple sclerosis ms perform systematic review metaanalysis existing literature assess pooled prevalence lesionlevel patientlevelmethods database searching pubmed embase handsearching conducted identify studies allowing lesionlevel patientlevel prevalence rim lesions chronic active lesions calculated pooled prevalence estimated using dersimonianlaird randomeffects model subgroup analysis metaregression performed explore possible sources heterogeneity prospero registration crd42020192282results 29 studies comprising 1230 patients eligible analysis metaanalysis estimated pooled prevalences 98 95 ci 66142 406 95 ci 262568 rim lesions lesionlevel patientlevel respectively pooled lesionlevel patientlevel prevalences chronic active lesions 120 95 ci 90158 648 95 ci 543740 respectively considerable heterogeneity observed across studies i275 subgroup analysis revealed significant difference patientlevel prevalence studies conducted 3t 7t p 00312 metaregression analyses also showed significant differences lesionlevel prevalence respect age p 00018 r2 020 disease duration p 00018 r2 048 moderator analyses demonstrated significant differences according mri sequence gender expanded disability status scale edss conclusion study show paramagnetic rim lesions may present important proportion ms patients notwithstanding significant variation assessment across studies view possible clinical relevance believe clear guidelines introduced standardise assessment across research centres turn facilitate future analysespmid34495999 doi101371 journalpone0256845,0.0
expert consensus identification diagnosis treatment neurotrophic keratopathy background neurotrophic keratopathy nk relatively uncommon underdiagnosed degenerative corneal disease caused damage ophthalmic branch trigeminal nerve conditions herpes simplex zoster keratitis intracranial spaceoccupying lesions diabetes neurosurgical procedures time epithelial breakdown corneal ulceration corneal melting thinning perforation loss vision may occur best opportunity reverse ocular surface damage earliest stage nk however patients typically experience symptoms diagnosis often delayed increased awareness causes nk consensus screen nk recommendations treat nk neededmethodsan 11member expert panel used validated methodology rand ucla modified delphi panel develop consensus screen best diagnose treat nk clinicians reviewed literature diagnosis management nk rated detailed set 735 scenarios 646 scenarios panelists rated whether test corneal sensitivity warranted 20 scenarios considered adequacy specific tests examinations diagnose stage nk 69 scenarios rated appropriateness treatments nk panelist ratings used develop clinical recommendationsresultsthere agreement 94 scenarios based consensus present distinct circumstances strongly recommend may consider test corneal sensitivity also present recommendations diagnostic tests performed patients nk suspected treatment options nkconclusionsthese expert recommendations validated clinical data recommendations represent consensus experts informed published literature experience may improve outcomes helping improve diagnosis treatment patients nk,0.0
racial ethnic disparities treatment response tolerability multiple sclerosis comparative study abstractbackgroundinterindividual response tolerability profiles associated available diseasemodifying treatments dmts important aspect therapeutic decisionmaking process multiple sclerosis ms absence racially diverse clinical studies possible effect race ethnicity treatment outcome remains uncertain study aims compare disease outcome among hispanic black white patients ms assess impact race ethnicity longterm outcomemethodsa retrospective review electronic medical records performed multiethnic cohort ms patients treated large academic center sociodemographic characteristics treatment regimens disability outcomes compared three groupsresultsa total 300 age gendermatched ms patients 100 hispanic 100 black 100 white included study assessing overall survival ms patients without ambulatory disability 5 years diagnosis hispanics blacks attained lower survival times compared whites survival time ratio str 017 p0004 014 p0002 respectively black patients highest rate disease progression treatmentlimiting adverse events despite similar sociodemographic profiles dmt exposure relative hispanics whitesconclusionracial ethnic disparities treatment outcome create unmet need identify tailored multifaceted approaches therapy selection ms,0.0
dietary intake characteristics persons multiple sclerosis abstractbackgrounddespite growing interest diet dietary interventions persons multiple sclerosis pwms studies examined dietary intake characteristics within population objectives study prospectively describe compare nutrition assessment parameters related diet including daily food intake nutrient intake eating behaviours dietary characteristics ie specific diets food preparation food security pwms controls without multiple sclerosis ms methodsthis study used crosssectional design 60 pwms 60 matched controls participants completed 3day food intake record questionnaires dietary intake analysed without supplements using esha food processor sql differences dietary intake group supplement intake examined using mixedmodel anovasresultsthere differences average daily micronutrient intake groups vitamins d b12 c omega 3 fatty acids phosphorous supplement use pwms consumed significantly vitamin d omega 3 fatty acids vitamin b12 vitamin c magnesium manganese zinc controls difference dietary behaviours dietary characteristics groupsconclusionsresults suggest dietary intake similar persons without ms differences dietary intake groups mostly accounted supplement intake pwms studies needed continue exploring dietary intake pwms,0.0
balancing potential benefits risks bruton tyrosine kinase inhibitor therapies multiple sclerosis covid19 pandemic neurol neuroimmunol neuroinflamm 2021 sep 8 8 6 e1067 doi 101212 nxi0000000000001067 print 2021 novabstractbruton tyrosine kinase inhibitors btkis encompass new class therapeutics currently evaluated treatment multiple sclerosis ms whether btkis affect covid19 risk severity reduce vaccine efficacy important unanswered questions provide overview btki mechanisms relevant covid19 infection vaccination review preliminary data btki use patients covid19 btkis block bcell receptor myeloid fragment crystallizable receptormediated signaling thereby dampening bcell activation antibody classswitching expansion cytokine production beyond antibodies covid19 severity vaccine efficacy appear largely linked tcell responses interferon induction processes directly affected btkis given b cells clear roles antigen presentation t cells however possible btkis may indirectly interfere beneficial detrimental tcell responses covid19 infection vaccination addition possible effects generating protective immune response btkis may attenuate hyperinflammatory dysregulation often seen severe cases covid19 evolves key risk factor disease currently available outcomes btkitreated patients covid19 discussed clinical trials currently underway evaluate safety efficacy btkis individuals ms although limited data suggest potential benefit btkis outcomes covid19 patients data adequately powered prospective randomized clinical trials lacking likewise specific effect btkis safety efficacy covid19 vaccines remains determined potential unknown risks btki therapy may present patient relative covid19 infection severity vaccine efficacy must balanced importance timely intervention prevent minimize ms progressionpmid34497100 doi101212 nxi0000000000001067,0.0
physical frailty cognitive impairment older nursing home residents latent class analysis background little known heterogeneous clinical profile physical frailty association cognitive impairment older us nursing home nh residentsmethodsminimum data set 30 admission used identify older adults newlyadmitted nursing homes life expectancy 6 months length stay 100 days n 871 801 latent class analysis used identify physical frailty subgroups using frailnh items indicators association identified physical frailty subgroups cognitive impairment measured brief interview mental status cognitive performance scale none mild moderate severe adjusting demographic clinical characteristics estimated multinomial logistic regression presented adjusted odds ratios aor 95 confidence intervals cis resultsin older nursing home residents admission three physical frailty subgroups identified mild physical frailty prevalence 76 moderate physical frailty 445 severe physical frailty 479 moderate physical frailty severe physical frailty high probabilities needing assistance transferring locations inability walk room residents severe physical frailty also greater probability bowel incontinence compared none mild cognitive impairment older residents moderate severe impairment slightly higher odds belonging moderate physical frailty aor 95ci moderate cognitive impairment 101 099103 aor 95ci severe cognitive impairment 103 101105 much higher odds severe physical frailty subgroup aor 95ci moderate cognitive impairment 241 235247 aor 95ci severe cognitive impairment 574 558590 conclusionsfindings indicate heterogeneous presentations physical frailty older nursing home residents additional evidence interrelationship physical frailty cognitive impairment,0.0
movement disorders multiple sclerosis demyelinating diseases retrospective review tertiary academic center neurologist 2021 sep 7 26 5 161166 doi 101097 nrl0000000000000333abstractbackground movement disorders mds described demyelinating diseases dds however data lacking effective treatment md well potential correlation dd lesions localization phenomenology md response treatmentmethods retrospective review 185 patients md dd seen center period 7 years clinical imaging medications therapeutic responses md dd treatments reviewedresults 185 patients 62 excluded diagnosis spasticity without md one hundred twenty three patients dd 75 female age 488128 y one md common md ataxia followed isolated tremor fortytwo patients 34 received treatment md 29 69 responded least partially first md agent 786 responded least partially second third agent responders first md therapy likely lesion basal ganglia cerebellum less likely lesion brainstem spinal cord results biased lowerthanexpected frequency tonic spasms series correlation dd lesions localization phenomenology md discoveredconclusions md common dd frequently overlooked undertreated md sample 69 therapeutic response first trial greater awareness potential therapeutic options needed decrease disabilitypmid34491930 doi101097 nrl0000000000000333,1.0
implications fda approval first diseasemodifying therapy neurodegenerative disease design subsequent clinical trials neurology 2021 jun 4101212 wnl0000000000012329 doi 101212 wnl0000000000012329 online ahead printabstractthe goal clinical research improve clinical practice progressive neurodegenerative conditions without diseaseslowing therapies will result eventual approval first diseasemodifying treatment clinical trials will still needed discover treatments effective safer convenient will generate controversies design trials specifically controversies use placebo control consider ethical guidance studies attention three designs placebocontrolled trials absence new drug placebocontrolled trials approved drug background therapy trials new drug activecontrol understand practical implications designs examine experiences drug development multiple sclerosis ms conclude contemplating future clinical trials alzheimers disease ad pmid34088880 doi101212 wnl0000000000012329,0.0
bcl6 controls meningeal th17b cell interaction murine neuroinflammation proc natl acad sci u s 2021 sep 7 118 36 e2023174118 doi 101073 pnas2023174118abstractectopic lymphoid tissue containing b cells forms meninges late stages human multiple sclerosis ms neuroinflammation induced interleukin il 17 producing t helper th17 cells rodents b cell differentiation subsequent release classswitched immunoglobulins speculated occur meninges exact cellular composition underlying mechanisms meningealdominated inflammation remain unknown performed indepth characterization meningeal versus parenchymal th17induced rodent neuroinflammation pronounced cellular transcriptional differences compartments localization b cells exhibiting follicular phenotype exclusively meninges correspondingly meningeal parenchymal th17 cells acquired b cellsupporting phenotype resided close contact b cells preferential b cell tropism meninges formation meningeal ectopic lymphoid tissue partially dependent expression transcription factor bcl6 th17 cells required t cell lineages induce isotype class switching b cells function bcl6 th17 cells detected vivo reflected induction b cellsupporting cytokines appearance follicular b cells meninges immunoglobulin class switching cerebrospinal fluid thus identify induction b cellsupporting meningeal microenvironment bcl6 th17 cells mechanism controlling compartment specificity neuroinflammationpmid34479995 doi101073 pnas2023174118,0.0
translational value choroid plexus imaging tracking neuroinflammation mice humans proc natl acad sci u s 2021 sep 7 118 36 e2025000118 doi 101073 pnas2025000118abstractneuroinflammation pathophysiological hallmark multiple sclerosis close mechanistic link neurodegeneration although link potentially targetable robust translatable models reliably quantify track neuroinflammation mice humans lacking choroid plexus chp plays pivotal role regulating trafficking immune cells brain parenchyma cerebrospinal fluid csf recently attracted attention key structure initiation inflammatory brain responses translational framework address integrity multidimensional characteristics chp inflammatory conditions question whether chp volumes act interspecies marker neuroinflammation closely interrelates functional impairment therefore explore chp characteristics neuroinflammation patients multiple sclerosis two experimental mouse models cuprizone dietrelated demyelination experimental autoimmune encephalomyelitis demonstrate chp enlargementreconstructed mriis highly associated acute disease activity studied mouse models humans close dependency chp integrity molecular signatures neuroinflammation shown performed transcriptomic analyses moreover pharmacological modulation bloodcsf barrier natalizumab prevents increase chp volume chp enlargement strongly linked emerging functional impairment depicted mouse models multiple sclerosis patients findings identify chp characteristics robust translatable hallmarks acute ongoing neuroinflammatory activity mice humans serve promising interspecies marker translational reversetranslational approachespmid34479997 doi101073 pnas2025000118,1.0
international headache congress ihs ehf joint congress 2021 n,0.0
foxo1 controls gut homeostasis commensalism regulating mucus secretion j exp med 2021 sep 6 218 9 e20210324 doi 101084 jem20210324 epub 2021 jul 21abstractmucus produced goblet cells gastrointestinal tract forms biological barrier protects intestine invasion commensals pathogens however hostderived regulatory network controls mucus secretion thereby changes gut microbiota well studied identify forkhead box protein o1 foxo1 regulates mucus secretion goblet cells determines intestinal homeostasis loss foxo1 intestinal epithelial cells iecs results defects goblet cell autophagy mucus secretion leading impaired gut microenvironment dysbiosis subsequently due changes microbiota disruption microbiome metabolites shortchain fatty acids foxo1 deficiency results altered organization tight junction proteins enhanced susceptibility intestinal inflammation study demonstrates foxo1 crucial iecs establish commensalism maintain intestinal barrier integrity regulating goblet cell functionpmid34287641 doi101084 jem20210324,0.0
tdp43 mediates srebf2regulated gene expression required oligodendrocyte myelination j cell biol 2021 sep 6 220 9 e201910213 doi 101083 jcb201910213 epub 2021 aug 4abstractcholesterol metabolism operates autonomously within central nervous system cns majority cholesterol resides myelin demonstrate tdp43 pathological signature protein amyotrophic lateral sclerosis als frontotemporal dementia ftd influences cholesterol metabolism oligodendrocytes tdp43 binds directly mrna srebf2 master transcription regulator cholesterol metabolism multiple mrnas encoding proteins responsible cholesterol biosynthesis uptake including hmgcr hmgcs1 ldlr tdp43 depletion leads reduced srebf2 ldlr expression cholesterol levels vitro vivo tdp43mediated changes cholesterol levels can restored reintroducing srebf2 ldlr additionally cholesterol supplementation rescues demyelination caused tdp43 deletion furthermore oligodendrocytes harboring tdp43 pathology ftd patients show reduced hmgcr hmgcs1 coaggregation ldlr tdp43 collectively results indicate tdp43 plays role cholesterol homeostasis oligodendrocytes cholesterol dysmetabolism may implicated tdp43 proteinopathiesrelated diseasespmid34347016 doi101083 jcb201910213,1.0
effect optic neuritis treatment trial ontt combined corticosteroid regimen pattern reversal visual evoked potentials prospective followup study background combined corticosteroid regimen original optic neuritis treatment trial ontt used many centers treat optic neuritis though pattern reversal visual evoked potentials prveps sensitive standard measure visual conduction optic neuritis studies hitherto investigated effect combined ontt regimen prveps aimed determine effect combined corticosteroid regimen ontt changes prveps patients firstepisode optic neuritis 3 months posttreatmentmethodsthis prospective observational study 44 patients optic neuritis seen pretreatment baseline followup 1 month fu1 3 months fu2 twentynine patients treated ontt combined regimen ontt+ group 15 conservatively managed without corticosteroids ontt group median latency amplitude values p100 prvep component visual acuity ie logmar values pretreatment fu1 fu2 compared two groups using friedmans rank test wilcoxon signed ranks testresultsmedian p100 latency improved significantly normal range early 1 month commencement treatment ontt+ group remained significantly lower baseline next 2 months ontt group median p100 latency improved slowly two follow assessments reached normal range 3 months median visual acuity values also improved significantly 1 3 months commencement treatment ontt+ group ontt groupconclusionontt combined corticosteroid regimen improves conduction visual pathways patients firstepisode optic neuritis earlier conservative management provide electrodiagnostic evidence combined ontt regimencompared conservative managementresults early remission visual conduction abnormalities firstepisode optic neuritis,0.0
increased tc17 cell levels imbalance nave#x2f effector immune response parkinsons disease patients twoyear followup case control study background neuroinflammation proved play role dopaminergic neuronal death parkinsons disease pd link highlights relevance immune response progression disease however little known impact peripheral immune response disease study aimed evaluate immune cell populations change untreated pd patients followedup 2 yearsmethodsthirtytwo patients previous treatment pd0 yr twentytwo healthy subjects controls included study pd patients sampled 1 2 years start treatment cd4 t cells nave central memory effector activated cd8 t cells activated central memory effector memory nkt tc1 tc2 tc17 b cells activated plasma lipap characterized flow cytometryresultswe observed decreased levels nave central memory cd4 cd8 t cells tc1 tc2 nkt plasma cells increased levels effector t cells activated t cells tc17conclusionspd patients treated 2 years showed imbalance naive effector immune response nave effector cell levels associated clinical deterioration populations also correlated aging hand higher tc17 levels suggest increased inflammatory response may impact progression disease results highlight relevant effect treatment immune response improve management disease,0.0
functional immune cellastrocyte interactions j exp med 2021 sep 6 218 9 e20202715 doi 101084 jem20202715 epub 2021 jul 22abstractastrocytes abundant glial cells central nervous system cns control multiple aspects health disease interactions components bloodbrain barrier bbb astrocytes regulate bbb function also sense molecules produced peripheral immune cells including cytokines review interactions immune cells astrocytes roles health neurological diseases special focus multiple sclerosis ms highlight known pathways participate astrocyte crosstalk microglia nk cells t cells cell types contribution pathogenesis neurological diseases potential value therapeutic targetspmid34292315 doi101084 jem20202715,0.0
wildtype fus corrects alslike disease induced cytoplasmic mutant fus autoregulation abstractmutations fus rnabinding protein involved multiple steps rna metabolism associated severe forms amyotrophic lateral sclerosis als accumulation cytoplasmic fus likely major culprit toxicity fus mutations thus preventing cytoplasmic mislocalization fus protein may represent valuable therapeutic strategy fus binds premrna creating autoregulatory loop efficiently buffering fus excess multiple proposed mechanisms including retention introns 6 7 introduced wildtype fus gene allele retaining intronic sequences mice whose heterozygous homozygous expression cytoplasmically retained fus protein fusnls previously shown provoke alslike disease postnatal lethality respectively wildtype fus completely rescued early lethality caused two fusnls alleles improved agedependent motor deficits reduced lifespan caused heterozygous expression mutant fusnls mechanistically wildtype fus decreased load cytoplasmic fus increased retention introns 6 7 endogenous mouse fus mrna decreased expression mutant mrna thus wildtype fus allele activates homeostatic autoregulatory loop maintaining constant fus levels decreasing mutant protein cytoplasm results provide proof concept autoregulatory competent wildtype fus expression protect devastating currently intractable neurodegenerative disease,0.0
associations exposure secondhand smoke hypertension risk blood pressure values adults background effects environmental chemical exposure blood pressure bp confirmed association exposure secondhand smoke shs hypertension risk bp general population remains unknownmethodscrosssectional associations shs exposure hypertension risk bp values evaluated using data subjects participated national health nutrition examination survey nhanes 19992016 logistic regression linear regression performed adjusting age sex race alcohol consumption povertytoincome ratio pir body mass index bmi estimated glomerular filtration rate physical activity diabetes cardiovascular disease nhanes cycle restricted cubic spline models created display potential nonlinear association shs bp levelsresultshigher risk hypertension found highest shs concentrations 113 95 ci 104 124 p trend 0007 additionally shs exposure strong positive association systolic blood pressure sbp negatively associated diastolic blood pressure dbp furthermore nonlinear model result showed significant association shs sbp p 0017 however nonlinear model result significant shs dbpconclusionsour results suggest potential association high shs exposure risk hypertension research needed elucidate underlying mechanisms,0.0
panppar agonist lanifibranor reduces development lung fibrosis attenuates cardiorespiratory manifestations transgenic mouse model systemic sclerosis background triikfib transgenic tg mouse model scleroderma replicates key fibrotic vasculopathic complications systemic sclerosis fibroblastdirected upregulation tgf signalling examined peroxisome proliferatoractivated receptor ppar pathway perturbation model explored impact panppar agonist lanifibranor cardiorespiratory phenotypemethodsppar pathway gene protein expression differences tg wt sexmatched littermate mice determined baseline following administration one two doses lanifibranor 30 mg kg 100 mg kg vehicle administered daily oral gavage 4 weeks prevention bleomycininduced lung fibrosis su5416induced pulmonary hypertension lanifibranor exploredresultsgene expression data consistent downregulation ppar pathway triikfib mouse model tg mice treated highdose lanifibranor demonstrated significant protection lung fibrosis bleomycin right ventricular hypertrophy following induction pulmonary hypertension su5416 despite significant change right ventricular systolic pressureconclusionsin triikfib mouse strain treatment 100 mg kg lanifibranor reduces development lung fibrosis right ventricular hypertrophy induced bleomycin su5416 respectively reduced ppar activity may contribute exaggerated fibroproliferative response tissue injury transgenic model scleroderma pulmonary complications,0.0
treatment delta9tetrahydrocannabinol#x2f cannabidiol multiple sclerosis influence autonomy profile according international classification functioning disability health eur j case rep intern med 2021 sep 6 8 9 002298 doi 1012890 2021_002298 ecollection 2021abstractmultiple sclerosis ms common cause nontraumatic neurological disability young adults effects different levels physical emotional psychological cognitive social great variety signs symptoms particular spasticity contributes reducing motor performance patients ms causing pain reduction distance walked limitations social life present case 39yearold woman ms treated delta9tetrahydrocannabinol cannabidiol outcome assessed international classification functioning disability health core set frameworklearning points clinical presentation multiple sclerosis ms heterogeneous often lower limb spasticity leads severe disabilitythe use nabiximols improved spasticity control motor performance walking also larger effect improving activity participation personal relationshipsappropriate assessment ms cases icf framework may demonstrate effects nabiximols patient capacity performancepmid34671570 pmcpmc8523373 doi1012890 2021_002298,0.0
deep brain stimulation multiple sclerosis tremor systematic review metaanalysis abstractobjectivethis systematic review metaanalysis aims evaluate efficacy deep brain stimulation dbs treating msrelated tremormethodswe systematically searched pubmed web science embase scopus google scholar gray literature using search strategy including mesh text words brain stimulations deep brain stimulations deep brain stimulations deep brain brain stimulation deep electrical stimulation brain multiple sclerosis sclerosis multiple sclerosis disseminated disseminated sclerosis ms multiple sclerosis multiple sclerosis acute fulminating resultsthe literature search revealed 1663 articles 1027 remained removing duplicates seventeen articles published 19992018 included metaanalysis including overall 168 patients followup time ranged 662 months pooled frequency tremor improvement among enrolled patients 73 95 ci6483 i2841 p0001 pooled standardized mean difference smd 29 95 ci48 098 i2898 p0001 conclusionthe results systematic review metaanalysis demonstrate msrelated tremor improvement dbs,0.0
pumas finetuning polygenic risk scores gwas summary statistics abstractpolygenic risk scores prss wide applications human genetics research often include tuning parameters difficult optimize practice due limited access individuallevel data introduce pumas novel method finetune prs models using summary statistics genomewide association studies gwass extensive simulations external validations analysis 65 traits demonstrate pumas can perform various modeltuning procedures using gwas summary statistics effectively benchmark optimize prs models diverse genetic architecture furthermore show finetuned prss will significantly improve statistical power downstream association analysis,0.0
influencing factors barthel index scores among communitydwelling elderly hong kong random intercept model background barthel index bi one widely utilized tools assessing functional independence activities daily living existing bi studies used populations specific diseases eg alzheimers stroke test prognostic factors bi scores however generalization findings limited target populations variedobjectivesthe aim present study utilize electronic health records ehrs data mining techniques develop generic procedure identifying prognostic factors influence bi score changes among communitydwelling elderlymethodslongitudinal data collected 113 older adults 81 females mean age 84 years sd 69 years hong kong elderly care centers visualization technologies used align annual bi scores individual ehrs chronologically linear mixedeffects lme regression conducted model longitudinal bi scores based sociodemographics disease conditions features extracted ehrsresultsthe visualization presented decline bi scores changed time health history events lme model yielded conditional r2 84 marginal r2 75 cohens f2 068 design random intercepts individual heterogeneity changes bi scores significantly influenced set sociodemographics ie sex education living arrangement hobbies disease conditions ie dementia diabetes mellitus ehrs features ie event counts allergies diagnoses accidents wounds hospital admissions injections etc conclusionsthe proposed visualization approach lme model estimation can help trace older adults bi score changes identify influencing factors constructed longterm surveillance system provides reference data clinical practice help healthcare providers manage time cost data human resources communitydwelling settings,0.0
simultaneous new onset neuromyelitis optica spectrum disorder identical twins bmj neurol open 2021 sep 6 3 2 e000174 doi 101136 bmjno2021000174 ecollection 2021abstractobjective present case two identical twins presenting concurrently symptoms subsequent initial diagnosis neuromyelitis optica spectrum disorder nmosd methods clinical laboratory mri findings twins reviewed presented hereresults twin presented right eye pain subsequent blurred vision right eye mri brain spine demonstrated prechiasmal right optic nerve enhancement t2 hyperintense lesions spinal cord t7 t9 levels cerebrospinal fluid csf analysis remarkable nmo aquaporin4 aqp4 fluorescenceactivated cell sorting facs titre 132 serum nmo aqp4igg positive titre 110 000 twin b presented diplopia mri brain spine demonstrated t2 hyperintense lesions periventricular cerebral white matter periaqueductal white matter pons midbrain cervical spinal cord neurological examination findings revealed incomplete right trochlear palsy rotatory nystagmus incomplete left internuclear ophthalmoplegia hyperreflexia csf analysis remarkable nmo aqp4 facs titre 1256 serum nmoigg positive titre 110 000 twins responded well intravenous steroid therapy adverse environmental exposure presentconclusion present interesting rare case identical twins presenting concurrently first time nmosdpmid34557671 pmcpmc8422323 doi101136 bmjno2021000174,0.0
engrailed 1 coordinates cytoskeletal reorganization induce myofibroblast differentiation j exp med 2021 sep 6 218 9 e20201916 doi 101084 jem20201916 epub 2021 jul 14abstracttransforming growth factor tgf key mediator fibroblast activation fibrotic diseases including systemic sclerosis show engrailed 1 en1 reexpressed multiple fibroblast subpopulations skin ssc patients characterize en1 molecular amplifier tgf signaling myofibroblast differentiation tgf induces en1 expression smad3dependent manner turn en1 mediates profibrotic effects tgf rna sequencing demonstrates en1 induces profibrotic gene expression profile functionally related cytoskeleton organization rock activation en1 regulates gene expression modulating activity sp1 sp transcription factors confirmed chipseq experiments en1 sp1 functional experiments confirm coordinating role en1 rock activity reorganization cytoskeleton myofibroblast differentiation standard fibroblast culture systems vitro skin models consistently mice fibroblastspecific knockout en1 demonstrate impaired fibroblasttomyofibroblast transition partially protected experimental skin fibrosispmid34259830 doi101084 jem20201916,0.0
multiparametric mri phenotype trustworthy machine learning differentiating cns demyelinating diseases background misdiagnosis multiple sclerosis ms neuromyelitis optica nmo may delay treatment resulting poor prognosis however precise identification two diseases still challenging clinical practice aimed evaluate value quantitative radiomic features extracted brain white matter lesions differential diagnosis ms nmomethodswe recruited 116 cns demyelinating patients including 78 ms 38 nmo three neuroradiologists performed visual differential diagnosis based brain mri comparison purpose multilevel scheme designed harness selection discriminative stable radiomics features extracted brain mater lesions t1mprage t2 sequences clinical factors based imaging phenotype composed selected radiomic clinical features multiparametric multivariate random forest mmrf model constructed verified 10fold crossvalidation independent testing result interpretation provided build trust diagnostic decisionsresultseightysix patients randomly selected form training set rest 30 patients independent testing training set mmrf model achieved accuracy 0849 auc 0826 10fold crossvalidation significantly higher clinical visual analysis 0709 0683 p 005 independent testing mmrf model achieved auc 0902 accuracy 0871 sensitivity 0873 specificity 0869 respectively furthermore age sex edss found mildly correlated radiomic features p 005 conclusionsmultiparametric radiomic features potential practical quantitative imaging biomarkers differentiating ms nmo,1.0
enigma implications brain hemispheric asymmetry neurodegenerative diseases brain commun 2021 sep 6 3 3 fcab211 doi 101093 braincomms fcab211 ecollection 2021abstractthe lateralization human brain may provide clues pathogenesis progression neurodegenerative diseases though differing presentation underlying pathologies neurodegenerative diseases devastating share intriguing theme asymmetrical pathology clinical symptoms parkinsons disease distinctive onset motor symptoms one side body stands regard review literature reveals asymmetries several neurodegenerative diseases review lateralization structure function healthy human brain common genetic epigenetic patterns contributing development asymmetry health disease specifically examine role asymmetry parkinsons disease alzheimers disease amyotrophic lateral sclerosis multiple sclerosis interrogate whether imbalances may reveal meaningful clues origins diseases also propose several hypotheses lateralization may contribute distinctive enigmatic features asymmetry neurodegenerative diseases suggesting role asymmetry choroid plexus neurochemistry protein distribution brain connectivity vagus nerve finally suggest future studies may reveal novel insights diseases lens asymmetrypmid34557668 pmcpmc8454206 doi101093 braincomms fcab211,0.0
computed tomography findings cohort 169 dogs elbow dysplasia retrospective study background canine elbow dysplasia ced complex developmental skeletal disorder associated number pathological conditions within cubital joint ced heritable disease important identify remove affected animals breeding first objective study describe prevalence medial coronoid process disease mcpd without mcd fmcp fragmented medial coronoid process osteochondrosis oc osteochondritis dissecans ocd ununited anconeal process uap radioulnar incongruence inc ru humeroulnar incongruence inc hu dogs use ct imaging second aim determine influence demographics prevalence investigated pathologies dogs clinical evidence elbow dysplasiaresultsin retrospective study ct data records 169 dogs different breeds presented small animal veterinary clinic 2012 2018 included 6923 dogs diagnosed ced young 2 years old mean age dogs presented inc ru 168 182 years dogs without inc ru mean age 264 259 years mean age dogs inc hu 194 206 years without inc hu 329 209 years labrador retrievers german shepherd bernese mountain dogs frequently presented cedassociated lameness 122 dogs oa varying severity foundconclusioninc hu fmcp mcd among frequently found components ced found present study ocd uap least frequently diagnosed dogs presented inc ru inc hu significantly younger dogs without ced components boxers dog de bordeaux american staffordshire terriers mixedbreed dogs diagnosed later life breeds oa varying severity found 7218 dogs males accounted 75 study population,0.0
genetically predicted circulating homocysteine vitamin b12 folate levels risk multiple sclerosis evidence twosample mendelian randomization analysis abstractthe association homocysteine risk multiple sclerosis ms remains unclear implemented twosample mendelian randomization mr analysis comprehensively investigate causal relationships circulating homocysteine vitamin b12 vitb12 folate levels ms data largescale genomewide association studies mr results demonstrated inverse association genetically predicted higher circulating homocysteine levels per 1 standard deviation sd increase risk ms 078 95 ci 064094 p00106 significant causal relationships genetically determined higher vitb12 folate levels ms observed studies warranted elucidate potential mechanisms,0.0
hospitaldiagnosed infections age 20 risk subsequent multiple sclerosis diagnosis brain 2021 mar 9awab100 doi 101093 brain awab100 online ahead printabstractthe involvement specific viral bacterial infections risk factors multiple sclerosis studied extensively however whether extends infections broader sense less clear little known whether risk multiple sclerosis diagnosis associated types sites infections cns study aims assess hospitaldiagnosed infections type site age 20 years associated risk subsequent multiple sclerosis diagnosis whether association explained entirely infectious mononucleosis pneumonia cns infections individuals born sweden 19701994 identified using swedish total population register n 2 422 969 multiple sclerosis diagnoses age 20 years hospitaldiagnosed infections age 20 years identified using swedish national patient register risk multiple sclerosis diagnosis associated various infections adolescence 1119 years earlier childhood birth10 years estimated using cox regression adjustment sex parental socioeconomic position infection type none infections age 10 years associated risk multiple sclerosis diagnosis infection adolescence increased risk multiple sclerosis diagnosis hazard ratio 133 95 confidence interval 121146 remained statistically significant exclusion infectious mononucleosis pneumonia cns infection hazard ratio 117 95 confidence interval 106130 cns infection adolescence excluding encephalomyelitis avoid including acute disseminated encephalitis increased risk multiple sclerosis diagnosis hazard ratio 185 95 confidence interval 111307 increased risk multiple sclerosis diagnosis associated viral infection adolescence largely explained infectious mononucleosis bacterial infections adolescence increased risk multiple sclerosis diagnosis magnitude risk reduced excluding infectious mononucleosis pneumonia cns infection hazard ratio 131 95 confidence interval 113151 respiratory infection adolescence also increased risk multiple sclerosis diagnosis hazard ratio 151 95 confidence interval 130175 statistically significant excluding infectious mononucleosis pneumonia findings suggest variety serious infections adolescence including novel evidence cns infections risk factors subsequent multiple sclerosis diagnosis demonstrating adolescence critical period susceptibility environmental exposures raise risk multiple sclerosis diagnosis importantly increased risk entirely explained infectious mononucleosis pneumonia cns infectionspmid33693538 doi101093 brain awab100,0.0
mog autoantibodies trigger tightlycontrolled fcr btkdriven microglia proliferative response brain 2021 jun 18awab231 doi 101093 brain awab231 online ahead printabstractautoantibodies hallmark numerous neurologic disorders including multiple sclerosis ms autoimmune encephalitides neuromyelitis optica nmo well understood peripheral myeloid cells pathophysiological significance autoantibodyinduced fc receptor fcr signaling microglia remains unknown part due lack robust vivo model moreover application therapeutic antibodies neurodegenerative disease also highlights importance understanding fcr signaling microglia describe novel vivo experimental paradigm allows selective engagement fc receptors within cns peripherally injecting antimyelin oligodendrocyte glycoprotein mog monoclonal antibodies mabs normal wildtype mice mog antigenbound immunoglobulins detected throughout cns triggered rapid tightly regulated proliferative response brain spinal cord microglia microglial response abrogated antimog antibodies deprived fc effector function injected fc r knockout mice associated downregulation fcrs microglia peripheral myeloid cells establishing response dependent central fcr engagement downstream fcrs brutons tyrosine kinase btk required signaling node response microglia proliferation amplified btke41k knockin mice expressing constitutively active form btk blunted mice treated cns penetrant small molecule inhibitor btk finally response associated transient stringently regulated changes gene expression predominantly related cellular proliferation markedly differed transcriptional programs typically associated fcr engagement peripheral myeloid cells together results establish physiologicallymeaningful functional response fcr btk signaling microglia providing novel vivo tool dissect roles microgliaspecific fcr btkdriven responses pathogenic therapeutic antibodies cns homeostasis diseasepmid34145876 doi101093 brain awab231,1.0
peripheral nervous system electrodiagnostic abnormalities predominantly hispanic multiple sclerosis patients abstractbackgroundperipheral nervous system pns abnormalities multiple sclerosis ms reported case reports small case series past several decades little known however prevalence electrodiagnostic abnormalities patients ms including demyelinating neuropathies chronic inflammatory demyelinating polyradiculoneuropathy cidp also axonal peripheral neuropathy sympathetic dysfunctionmethodsthis observational crosssectional study objective identifying prevalence electrodiagnostic abnormalities predominantly hispanic ms patients miami florida electrodiagnostic data including nerve conduction study ncs electromyography emg sympathetic skin response ssr information prospectively collected 18 patients 16 females 437152 years diagnosis ms compared 18 healthy 16 females 39911 years age heightmatched controls study offered allcomers ms clinic period 3 months regardless clinical suspicion underlying neuropathic process effort estimate prevalence abnormalities demographic data including age sex race ethnicity evaluated addition msspecific characteristics including ms subtype duration disease duration therapy clinical symptoms laboratory dataresultsthere significant differences baseline characteristics patients controls age p04 height 164064 vs 162346 centimeters p03 mean disease duration 10627 months median 107 months range 5336 months mean expanded disability status scale edss 24187 median 25 range 1065 ethnicity patients 15 hispanic 3 nonhispanic controls 13 hispanic 5 nonhispanic p056 similar frequency electrophysiological axonal polyneuropathy pn 778 14 18 patients 856 patients clinical sensory symptoms interestingly 1 patient previously unrecognized cidp 18 patients displayed prolonged ssr latencies consistent autonomic dysfunction thirteen patients 722 reported autonomic symptoms bladder abnormalities blood pressure fluctuationsconclusionthe prevalence electrodiagnostic abnormalities especially axonal polyneuropathy ms population may higher traditionally considered relationship axonal polyneuropathy central axonopathy context neurodegeneration ms explored analytic studies may identify common symptomatic pathophysiologic etiologies understanding potentially guide treatment ms subtypes pns involvement,1.0
macular xanthophylls markers anterior visual pathway among persons multiple sclerosis j nutr 2021 jun 4nxab164 doi 101093 jn nxab164 online ahead printabstractbackground multiple sclerosis ms can cause retinal thinning among persons ms optic neuritis mson macular xanthophylls carotenoids comprise macular pigment filtering blue light countering photooxidation however macular xanthophyll status implications markers neuroaxonal degeneration examined msobjectives study characterized differences macular serum xanthophylls retinal morphometry retinal nerve fiber layer thickness macular mrnfl optic disc odrnfl total macular volume tmv individuals ms healthy controls hc associations macular pigment optical density mpod retinal morphometry also examinedmethods adults aged 4564 y hc n 42 ms n 40 participated crosssectional study mpod measured via heterochromatic flicker photometry retinal morphometry measured via optical coherence tomography oct serum carotenoids quantified using hplc dietary carotenoids collected using 7d records onefactor anova conducted determine group effects macular serum dietary carotenoids partial correlations examined relations mpod retinal morphometry diet serum carotenoidsresults relative hc persons mson lower mpod cohens d 084 p 0014 lower odrnfl cohens d 216 p 0001 lower mrnfl cohens d 057 p 0028 lower tmv cohens d 095 p 0011 ms without ms lower odrnfl cohens d 093 p 0001 hc lower serum lutein mson subjects cohens d 065 p 0014 among ms mpod positively correlated odrnfl thickness 043 p 0049 tmv 045 p 0039 whereas odrnfl negatively correlated serum lutein 068 p 0016 zeaxanthin 062 p 0028 conclusions persons mson exhibited poorer xanthophyll status macula serum mpod associated beneficial anatomical features ms group findings warrant confirmation larger cohorts prospective trials evaluate xanthophyll effects anterior visual pathway mspmid34087931 doi101093 jn nxab164,0.0
high titers myelin oligodendrocyte glycoprotein antibody observed close clinical events pediatrics abstractbackgroundmyelin oligodendrocyte glycoprotein mog igg increasingly detected children cns demyelinating diseases due clinical overlap children cns demyelination without mogigg positivity identifying distinct characteristics help early diagnosisobjectiveto compare specific features may help differentiate mogigg positive negative children cns demyelinating diseases compare characteristics patients high low mogigg titersmethodschildren cns demyelinating disorders onset 18 years age tested mogigg university california san francisco included retrospective study collected following chart review demographic clinical mri csf treatment data serum tested mogigg mayo clinic live cellbased fluorescent activated cell sorting assay titer 120 confirming positivityresultswe assessed 65 mogigg positive 65 mogigg negative patients median iqr age onset 76 66 years mogigg positive 138 58 years mogigg negative p0001 female male ratio approximately 11 mogigg positive group 31 negative group p0042 common initial diagnosis demyelinating disease otherwise specified 523 positive group compared relapsingremitting multiple sclerosis 415 negative group p001 optic nerve involvement 523 common clinical localization onset mogigg positive group brainstem cerebellar 492 localization predominated mogigg negative group positive group also presented often severe event disease onset negative group 815 vs 603 p 0002 mogigg positive children lower frequency oligoclonal bands 158 vs 574 p0001 frequency baseline brain spinal cord mri abnormalities similar groups however mogigg positive patients often t2 hyperintense lesions optic nerves 26 43 vs 10 41 p0001 diseasemodifying medications used 646 mogigg positive patients versus 80 negative children 32 positive patients followup titers seven reverted negative two tested negative initially converted positive positive titers greater 1160 observed within four months clinical event disease onset relapse patients high low mogigg titers comparable demographic clinical characteristicsconclusiondespite clinical overlap report notable demographic mri csf differences mogigg positive negative children cns demyelinating disorders disease onset high mogigg titers observed close clinical event,1.0
bmp receptor blockade overcomes extrinsic inhibition remyelination restores neurovascular homeostasis brain 2021 aug 24awab106 doi 101093 brain awab106 online ahead printabstractextrinsic inhibitors sites bloodbrain barrier disruption neurovascular damage contribute remyelination failure neurological diseases however therapies overcome extrinsic inhibition remyelination widely available dynamics glial progenitor niche remodeling sites neurovascular dysfunction largely unknown integrating vivo twophoton imaging coregistered electron microscopy transcriptomics chronic neuroinflammatory lesions found oligodendrocyte precursor cells clustered perivascularly sites limited remyelination deposition fibrinogen blood coagulation factor abundantly deposited multiple sclerosis lesions developing screen opcxscreen identify compounds promote remyelination presence extrinsic inhibitors showed known promyelinating drugs rescue extrinsic inhibition remyelination fibrinogen contrast bone morphogenetic protein type receptor blockade rescued inhibitory fibrinogen effects restored promyelinating progenitor niche promoting myelinating oligodendrocytes suppressing astrocyte cell fate potent therapeutic effects chronic models multiple sclerosis thus abortive oligodendrocyte precursor cell differentiation fibrinogen refractory known promyelinating compounds suggesting blockade bone morphogenetic protein signalling pathway may enhance remyelinating efficacy overcoming extrinsic inhibition neuroinflammatory lesions vascular damagepmid34426831 doi101093 brain awab106,1.0
slowly expanding lesions marker progressive ms yes 20ycars ago john princas colleaguesdescribed neuropathology chronic active slowly expanding lesions secondary progressivemultiple sclerosis ms autopsy cases pointing outtheir potential pathogencetic relevance disease progression ms characteristic pathological featureof lesions rim activated microglia macrophages surrounding inactive lesion center withonly microglia macrophages phagocytesat chronic active lesion edge prerequisite ofiron accumulation rarely seen aroundinactive absent remyelinated lesions largeneuropathological studies predominantly found thistype chronic lesions progressive ms cases highlighting persistence chronic inflammatory activity behind partially repaired bloodbrainbarrier inthe later stage msthe possibility visualize vivo using different imaging strategies far recent postmortemvalidation confirmed susceptibilitybased magnetic resonance imaging mri techniques phase swi qsm 3 tesla 7 tesla mri candetect ironladen microglia macrophages paramagnetic rims around lesions therefore termed paramagnetic rim lesions prl 4 vivovisualization prl increasingly found also inrelapsing patients naturally less present inms autopsy cohorts vivo longitudinal mri studiesfurthermore confirmed pathohistological assumption smoldering demyelination edgeleads slow lesion expansion vivo underscoringthe term slowly expanding lesions sels conversely chronic lesions without paramagneticrims showed completely different volumetrajectory shrink time least positron emission tomography pet mri studies filling gap neuropathology invivo imaging recently confirmed significantlyhigher vivo pathohistological tspo expression activated microglia macrophages astrocytes inrim lesionsgrowing evidences support notion prl selsare specific ms also pathologicalradiological marker progressive ms overallprevalence across larger cohort studies estimatedaround 50 ms patients agreement neuropathological studies slightly higher prl prevalence 6065 progressive patients atleast prl well higher sels counts volumeshave confirmed vivo progressive ms sdespite tendency paramagnetic rimsto fade several years prl also largely present relapsing ms 5055 patients andthey associated higher disability scoresand transition progression date one study evaluated detected low frequencyof prl cis carly relapsing ms 13 66 patientshad least 1 prl 20 interestingly recentlypublished cohort ris presented perivenular lesionsand unexpected high number prl 17 28 61 ris cases least prl supportingthe idea untreated asymptomatic cases partof ms spectrum can retain chronic active inflammation sense extreme interest see clinical evolution particular whetherthey will convert primary progressive msseveral studies specifically interrogated association prl sels disability accrual orclinical progression reanalysis phase hi clinical trial oratrio showed sels acerual overtime independently associated disabilityprogression primary progressive ms n 732 multicenter crosssectional dataset 329 mspatients number prl positively correlated disability severity scores expanded disability status scale edss multiplesclerosis severity scale msss global agerelated multiple sclerosis severity armss including lower cognitive performance prl association msss armss confirms thatrelapsing ms patients harboring several prl risk toreach higher disability scores even transition,1.0
slowly expanding lesions marker progressive multiple sclerosis commentary controversy prominent opponents debatewhether slowly expanding lesions sels amarker progressive multiple sclerosis ms notthis topic important many uttermost fortwo reasonsfirst tackles problem despite advancesin magnetic resonance imaging mri stilllacking imaging markers high pathological specificity second debate discusses potential toolto better characterize progressive stages ms wherenow fortunately treatment options exist yet weleamed recently progression independent ofrelapse activity pira significantly contributes todisability accumulation also relapsing ms wetherefore need better understand factors contribute progression enigmatic disease least marker heralding behelpfulsince first application mri ms london 40years ago using noninvasive technique monitor discase vivo identify markers specificpathophysiological processes center ofinterest surprisingly carly autopsy twopatients secondary progressive ms ongoing,0.0
comorbidity persistence diseasemodifying therapy use relapsing remitting multiple sclerosis abstractbackgroundcomorbidity decreases likelihood initiating diseasemodifying therapy dmt multiple sclerosis ms objective characterize relationship comorbidity initial dmt persistence along reasons dmt discontinuationmethodswe identified individuals relapsing remitting ms clinically isolated syndrome starting platform dmt interferon glatiramer acetate dimethyl fumarate teriflunomide initial therapy canadian province nova scotia 2001 2016 cases identified using clinic database clinic providing specialty ms care province universal publiclyfunded health care comorbidity determined linkage ms cases provincial health administrative data using validated case definitions mental health disorder hypertension hyperlipidemia diabetes chronic lung disease ischemic heart disease epilepsy inflammatory bowel disease cox proportional hazards models explored relationship comorbidity count individual comorbidities time discontinuation initial dmt logistic regression models explored reasons dmt discontinuationresultsamong 1464 individuals starting platform therapy initial dmt median duration first dmt 4 years 95 ci 4 4 comorbidity count 0 1 2 associated time discontinuation initial dmt however presence mental health disorder associated increased hazard discontinuing dmt hazard ratio 122 95 ci 103144 comorbidity count associated discontinuation lack efficacy lack tolerability adjusting covariatesconclusionindividuals mental health comorbidity may unique challenges affect persistence dmt treatment initiation,0.0
wearable inertial sensors highly sensitive detection gait disturbances fatigue early stages multiple sclerosis background aim current study examine multiple gait parameters obtained wearable inertial sensors sensitivity clinical status early multiple sclerosis ms potential correlation gait parameters subjective fatigue exploredmethodsautomated gait analyses carried 88 ms patients 31 healthy participants measure gait parameters ie walking speed stride length stride duration duration stance swing phase minimal toetofloor distance wearable inertial sensors utilized throughout 6min 25ft walk additionally selfreported subjective fatigue assessedresultsmean gait parameters consistently revealed significant differences healthy participants ms patients early expanded disability status scale edss value 15 onwards ms patients showed significant linear trend parameters reflecting continuously deteriorating gait performance throughout test linear deterioration trend showed significant correlations fatigueconclusionswearable inertial sensors highly sensitive detection gait disturbances even early ms global scales edss provide clinical information deviations gait behavior moreover measures provide linear trend parameter gait deterioration may serve surrogate marker fatigue sum results suggest classic timed walking tests routine clinical practice replaced readily automatically applicable gait assessments provided inertial sensors,0.0
serum cxcl10 ip10 may potential biomarker severe mycoplasma pneumoniae pneumonia children background early distinguish severity mycoplasma pneumoniae pneumonia mpp worldwide concern clinical practice therefore conducted study assess relationship levels serum inflammatory chemokines severity mppmethods prospective study enrolled 39 children mpp whose clinical information collected blood samples assayed cytokines chemokines elisaresultsthe levels serum cxcl10 children severe mpp significantly higher children mild mpp 25000 1580925000 vs 6757 394711349 p 0001 measurement cxcl10 levels serum enabled differentiation children severe mpp area curve auc 0885 95 ci 07790991 p 0001 sensitivity 810 specificity 833 conclusionsserum cxcl10 level may potential biomarker severe mpp children,0.0
staging astrocytopathy complement activation neuromyelitis optica spectrum disorders brain 2021 mar 12awab102 doi 101093 brain awab102 online ahead printabstractaquaporin 4 aqp4 iggpositive neuromyelitis optica spectrum disorder aqp4igg+nmosd autoimmune astrocytopathic disease pathologically characterized massive destruction regeneration astrocytes diverse types tissue injury without complement deposition however unknown whether diversity derived differences pathological processes temporal changes furthermore unlike demyelinating lesions multiple sclerosis staging astrocytopathy aqp4igg+nmosd based astrocyte morphology therefore classified astrocytopathy disease comparing characteristic features aqp4 loss inflammatory cell infiltration complement deposition demyelination activity clinical phase performed histopathological analyses eight autopsied cases aqp4igg+nmosd six women two men median age 565 years range 4671 years median disease duration 625 months range 06252 months astrocytopathy aqp4igg+nmosd classified following four stages defined astrocyte morphology immunoreactivity glial fibrillary acidic protein gfap astrocyte lysis extensive loss astrocytes fragmented dustlike particles b progenitor recruitment loss astrocytes except small nucleated cells gfappositive fibreforming foot processes c protoplasmic gliosis presence starshaped astrocytes abundant gfapreactive cytoplasm d fibrous gliosis lesions composed densely packed mature astrocytes astrocyte lysis progenitor recruitment stages dominated clinically acute cases within 2 months last recurrence findings common stages loss aqp4 decreased number oligodendrocytes selective loss myelinassociated glycoprotein active demyelination phagocytic macrophages infiltration polymorphonuclear cells t cells cd4dominant deposition activated complement c9neo reflects membrane attack complex hallmark acute nmosd lesions selectively observed astrocyte lysis stage 984 astrocyte lysis 16 progenitor recruitment 0 protoplasmic gliosis fibrous gliosis although protoplasmic gliosis fibrous gliosis lesions accompanied inactive demyelinated lesions low amount inflammatory cell infiltration deposition complement degradation product c3d observed four stages even fibrous gliosis lesions suggesting past chronic occurrence complement activation useful finding distinguish chronic lesions nmosd multiple sclerosis staging astrocytopathy expected useful understanding unique temporal pathology aqp4igg+nmosdpmid33711152 doi101093 brain awab102,1.0
acute onset anarthria 7yearold patient presentation acute disseminated encephalomyelitis rare clinical radiological entity radiol case rep 2021 sep 4 16 11 34183421 doi 101016 jradcr202108016 ecollection 2021 novabstractacute disseminated encephalomyelitis adem also called postinfectious encephalomyelitis defined immunemediated inflammatory demyelinating event involves central nervous system usually follows infectious episode active immunization several weeks prior disease onset adem typically presented encephalopathy associated focal neurological signs cerebrospinal fluid analysis usually nonspecific showing signs central nervous system inflammation negative viral bacterial cultures diagnosis based clinical mri findings patients adem respond well antiinflammatory immunosuppressive agents highdose intravenous steroids administered firstline treatment herein present case 7yearold male patient diagnosed acute disseminated encephalomyelitis likely secondary viral upper respiratory tract infection unique case inaugurating sign acute onset anarthria patient responded favorably firstline therapy almost full recovery within first week treatmentpmid34522279 pmcpmc8426168 doi101016 jradcr202108016,1.0
slowly expanding lesions marker progressive ms recent years highly effective therapies developed can essentially stop formation new white matter wm lesions multiple sclerosis ms unfortunately efficacy therapy prevent formation new lesions visible magnetic resonance imaging mri associated comparable efficacy preventing development confirmed disability progression example ocrelizumab suppresses new enlarging lesion formation 90 reduces confirmed disability progression 251the reason disparity like cause s progressive disability remains unclear one candidate chronic inflammation continues damage myelin axons within preexisting lesions variably referred chronic active lesions mixed active inactive lesions smouldering lesions slowly expanding lesions sels characterization histologically defined chronic active lesions slowly expanding based assumption observed rim activated microglia associated expansion lesion life will use term chronic active lesions refer lesions defined histologically distinguish sels defined mrimri detection chronic active lesionschanges time within existing ms lesions poorly characterized conventional mri typically identified foci hyperintensity t2weighted images binary classification indifferent ongoing pathological changes within lesions special techniques required detect chronic activity vivophaserim lesionsone approach based detection iron associated activated microglia periphery lesions done using susceptibilityweighted imaging identify lesions paramagnetic phase rims lesions referred phaserim lesions prls ironrim lesions probably correspond 40 chronic active lesions associated iron accumulation2 prls found forms ms looked progressive multiple sclerosis pms relapsing multiple sclerosis rms even radiologically isolated syndrome selsa second approach based detection sels directly conventional mri scans3 approach uses calculated deformation fields detect foci gradual concentric expansion within existing t2lesions serial mri scansit important appreciate approach detection lesion expansion fundamentally different used detection socalled enlarging lesions commonly reported counts new enlarging t2 lesions clinical trials methods detection enlarging lesions context new enlarging lesion counts vary laboratory laboratory designed detect essentially new foci acute activity connected areas existing t2signal abnormality therefore qualify de novo new lesions definition surrounded normalappearing wm mri used detect sels large number people ms representing different populationselliott et al3 reported sels 1344 rms 555 primary progressive multiple sclerosis ppms subjects pooled populations two identical phase iii multicenter randomized doubleblind doubledummy parallelgroup opera opera ii trials opera nct01247324 opera ii nct01412333 phase iii randomized placebocontrolled doubleblind multicenter oratorio trial nct01194570 compared subjects rms subjects ppms slightly higher numbers sels 63 vs 46 proportion baseline t2weighted lesion volume identified sels 113 vs 86 differences remained significant adjusting age gender expanded disability status scale edss score data file suggesting sels increase slightly ms becomes clinically progressive treatment effect computed oratorio patients ocrelizumab showed effect reducing overall accumulation damage within preexisting lesions including sels effect modestthe methodology applied independent data set including subject relapsingremitting multiple sclerosis rrms spms4 identified 1 sel majority patients groups spms 89 rrms 83 spms population tended higher numbers volume sels differences significant groups tissue destruction evidenced lower magnetisation transfer ratio lower normalized t1 intensity higher radial diffusivity greater sels t2 lesion volume outside sels4similar observations sels made others secondary progressive ms5 rrms patients treated fingolimod natalizumab6 taking account fact volume number sels measured different laboratories directly comparable due use different detection algorithms histopathology evidence sels marker pmschronic active lesions detected postmortem commonly found progressive ms5 however also present rms 7 estimates greater prevalence chronic active lesions pms based postmortem studies interpreted light observational bias associated fact patients rrms usually develop pms die mri provides means detecting sels vivo avoids bias associated postmortem studies sels show partial correspondence prls suggesting sels without phase rims prls without slow expansion represent different aspects stages ms pathology within chronic active lesions8the mri evidence sels marker progression rms well pmssels shown predict progression ppms 9 long known increases disability occur independent relapse activity recently become clear majority increase disability rms also occurs independent relapse activity 10 sel volume associated form progression ocrelizumabtreated rms subjects opera trials t1 lesion volume associated sels baseline predicted disease progression extension phase trials data file conclusionthus mri data support proposition sels specific marker pms traditionally defined clinically rather indicate marker progressive biology increasingly appreciated occur onset ms throughout disease coursedeclaration conflicting intereststhe author s declared following potential conflicts interest respect research authorship publication article dla received personal compensation serving consultant alexion biogen celgene frequency therapeutics geneuro genentech merck emd serono novartis roche sanofi ownership interest neurorx sb ag employees shareholders biogen lg employee shareholder f hoffmannla roche cb contractor f hoffmanla roche ce employee neurorx,1.0
cannabis chronic musculoskeletal pain scoping review users perceptions background chronic musculoskeletal pain cmp may lead reduced physical function common cause chronic noncancer pain currently pharmacotherapeutic options cmp limited frequently consist pain management nonsteroidal antiinflammatories gabapentinoids opioids carry major adverse effects although effectiveness medical cannabis mc cmp still lacks solid evidence several patients suffering exploring therapeutic option physiciansobjectiveslittle known patients perceptions mc treatment cmp aimed increase knowledge useful healthcare professionals patients considering treatment conducting scoping literature review following guidance arksey omalley describe views perceptions adult patients consumed mc relieve chronic cmpmethodsdatabases pubmed embase web science websites searched using combinations controlled free vocabulary studies study designs reporting patients perceptions regarding mc cmp considered studies include adult patients reporting qualitatively quantitatively ie questionnaires mc use treat cmp noncancer pain since studies reporting exclusively perceptions regarding cmp rare study characteristics extracted limitations study quality assessed review includes patients demographic characteristics patterns mc use perceived positive negative effects use alcohol drugs reported barriers cm use funding sources studiesresultsparticipants 49 included studies reported mc use helped reduce cmp chronic noncancer pain minor adverse effects reported improved psychological wellbeingin included studies men represent 18 88 subjects mean age participants studies 42 49 varied 284 628 years old common route administration inhalationconclusionmc users suffering cmp chronic noncancer pain perceived benefits harms however information studies several methodological limitations results exploratory userreported experiences must thus examined welldesigned methodologically sound clinical observational studies particularly regarding cmp reports scarce,0.0
antiviral immunomodulatory interferonbeta highrisk covid19 patients structured summary study protocol randomised controlled trial abstractobjectivesthe primary objective study demonstrate efficacy lowdose ifn reducing risk sarscov2 recently infected elderly patients progress towards severe covid19 versus control group within 28 days secondary objectives 1 assess reduction intensive care unit icu admission patients treated ifn versus control group within 28 days randomization 2 assess reduction number deaths ifn compared control group day 28 3 evaluate increase proportion participants returning negative sarscov2 rtpcr ifn treated versus control group day 14 day 28 4 assess increase sarscov2specific binding antibody titers ifn compared control group day 28 5 assess safety ifn treated patients versus control group trial designrandomized openlabel controlled superiority phase ii study patients satisfy inclusion criteria exclusion criteria will randomly assigned one two treatment groups ratio 21 ifntreated versus control patients randomization will stratified gender stratified randomization will balance presence male female study armsparticipantsmale female adults aged 65 years older newly diagnosed sarscov2 infection mild covid19 symptoms eligible study trial conducted romeparticipants will either hospitalized home isolated group physicians belonging special unit regional continued care uscar specifically trained study supervision national institute infectious diseases lazzaro spallanzani will responsible screening enrolment treatment clinical monitoring patients thus acting bridge clinical centers territorial health managementinclusion criteria follows 65 years age time enrolment laboratoryconfirmed sarscov2 infection determined pcr specimen 72 hours prior randomization subject legally authorized representative provides written informed consent prior initiation study procedures understands agrees comply planned study procedures agrees collection nasopharyngeal swabs venous blood samples per protocol symptomatic less 7 days starting therapy news2 score 2 exclusion criteria follows hospitalized patients illness duration least one following clinical assessment evidence rales crackles exam spo2 94 room air rest walking test acute respiratory failure requiring mechanical ventilation supplemental oxygen patients currently using ifn eg multiple sclerosis patients patients undergoing chemotherapy immunosuppressive treatments patients chronic kidney diseases known allergy hypersensitivity ifn including asthma autoimmune disease resulting patient anamnesis patients signs dementia neurocognitive disorders patients current severe depression suicidal ideations concurrently involved another clinical trial hiv infection based anamnesis use antiretroviral medication impaired renal function egfr calculated ckdepi creatinine equation 30 ml min presence severe diseases impairing life expectancy eg patients expected survive 28 days given preexisting medical condition physical psychological impediment patient let investigator suspect poor compliance lack withdrawal informed consent intervention comparatorcontrol arm specific antiviral treatment besides standard caretreatment arm 11g 3miu ifn1a will injected subcutaneously day 1 3 7 10 addition standard care drug solution contained prefilled cartridge will injected means rebismart electronic injection deviceinterferon 1a rebif merck kgaa darmstadt germany diseasemodifying drug used treat relapsing forms multiple sclerosis ms dose selected study expected exploit antiviral immunomodulatory properties cytokine without causing relevant toxicity inducing refractoriness phenomena sometimes observed highdose chronic ifn treatmentsmain outcomesprimary endpoint study proportion patients experiencing disease progression least 5 days according national early warning score news2 news2 score standardized approach aimed promptly detecting signs clinical deterioration acutely ill patients establishing potential need higher level care based evaluation vital signs including respiratory rate oxygen saturation temperature blood pressure pulse heart rate avpu response resulting observations compared normal range combined single composite alarm score clinical sign clearly indicating disease worsening will considered disease progressionrandomizationsixty patients will randomized 21 receive ifn1a plus standard care standard care eligible patients will randomized later 36 h enrolment means computerized central randomization system patients will receive unique patient identification number enrolling visit signing informed consent study procedure performed number remains constant throughout entire study randomization patients will closed 60 patients enrolled randomization will stratified sex stratum sequence treatments randomly permuted blocks variable length 3 6 will generatedblinding masking openlabel study randomization patients will notified whether will experimental arm control armnumbers randomised sample size study plans enrol 60 patients 40 ifn1a arm 20 control arm according 21 treated untreated ratiotrial statusprotocol version 30version date 18 03 2021the study open recruitment since 16 04 2021recruitment expected l completed 15 08 2021trial registrationeudract n 202000387242 registration date 19 10 2020full protocolthe full protocol attached additional file accessible trials website additional file 1 interest expediting dissemination material familiar formatting eliminated letter serves summary key elements full protocol,0.0
interaction epsteinbarr virus encoded transcription factor ebna2 multiple sclerosis risk loci dependent risk genotype abstractbackgroundepsteinbarr virus ebv infection may necessary development multiple sclerosis ms earlier identified six ms risk loci colocated binding sites ebv transcription factor epsteinbarr nuclear antigen 2 ebna2 ebvinfected b cells lymphoblastoid cell lines lcls methodswe used allelespecific chromatin immunoprecipitation pcr assay assess ebna2 allelic preference treated lcls peptide inhibitor ebna2 ebna2tat reasoning inhibiting ebna2 function alter gene expression loci mediated ebna2findingswe found ebna2 binding dependent risk allele five six ms risk loci p 005 treatment ebna2tat significantly altered expression traf3 p 005 cd40 p 0001 clecl1 p 00001 tnfaip8 p 0001 tnfrsf1a p 0001 interpretationthese data suggest ebna2 can enhance reduce expression gene depending risk allele likely promoting ebv infection consistent concept ms risk loci affect ms risk altering response ebna2 together extensive data indicating pathogenic role ebv ms study supports targeting ebv ebna2 reduce effect ms pathogenesisfundingfunding provided grants ms research australia national health medical research council australia australian government research training program multiple sclerosis international federation trish multiple sclerosis research foundation,0.0
immunomodulatory effect standardized c asiatica extract promotion regulatory t cells rats background eca 233 standardized extract c asiatica containing triterpenoid glycosides madecassoside asiaticoside ratio 15 05 1 antiinflammatory activities eca 233 reported however immunomodulatory effects eca 233 regulatory t cells pivotal role immune regulation elucidated therefore investigated effects eca 233 regulatory t cells may provide benefits autoimmune chronic inflammatory diseasesmethodseca 233 prepared oral suspension 05 carboxymethylcellulose administered male wistar rats via oral gavage pharmacokinetics toxicity eca 233 evaluated splenic lymphocytes isolated analyzed flow cytometry qpcr determine immunomodulatory effects eca 233 regulatory t cellsresultsall rats good tolerability eca 233 test preparations pharmacokinetic study showed low oral bioavailability triterpenoids maximum plasma concentration reached 4 h asiaticoside 05 h madecassoside multiple oral administration eca 233 reduced frequency t cells particularly cd8 t cells rats eca 233 enhanced percentage regulatory t cells characterized high expression cd25+ upregulation foxp3 geneconclusionsthe present study demonstrated eca 233 possesses immunosuppressive properties enhancing regulatory t cells results provide vivo evidence antiinflammatory action eca 233 line previously reports potential uses eca 233 treatment chronic inflammatory autoimmune diseases,0.0
2021 recommendations brazilian society rheumatology gynecological obstetric care patients sjogrens syndrome abstractsjogrens syndrome ss autoimmune disease characterized lymphocytic infiltration exocrine glands organs women ss often experience gynecological symptoms due disease need extra care regarding sexual activity reproductive health pregnancy conditions properly conducted clinical practice cover gap panel experts brazilian society rheumatology conducted systematic review metaanalysis identification symptoms diagnosis monitoring prognosis treatment manifestations focus group meeting held included experts field methodologists based previously developed script themes related objective study important topics summarized 11 recommendations provided,0.0
transcriptome analysis provides genome annotation expression profiles central nervous system lymnaea stagnalis different ages background pond snail lymnaea stagnalis l stagnalis served valuable model organism neurobiology studies due simple easily accessible central nervous system cns l stagnalis widely used study neuronal networks recently gained popularity study aging neurodegenerative diseases however previous transcriptome studies l stagnalis cns exclusively carried adult l stagnalis part ongoing effort studying l stagnalis neuronal growth connectivity various developmental stages provide first agespecific transcriptome analysis gene annotation young 3 months adult 6 months old 18 months l stagnalis cnsresultsusing three age cohorts study generated 5569 millions 150 bp pairedend rna sequencing reads using illumina novaseq 6000 platform reads 74 successfully mapped reference genome l stagnalis referencebased transcriptome assembly predicted 42 478 gene loci 37 661 genes encode coding sequences cds least 100 codons addition provide gene annotations using blast2go functional annotations using pfam 95 sequences contributing largest number annotated genes l stagnalis cns far moreover among 242 previously cloned l stagnalis genes able match 87 transcriptome assembly indicating high percentage gene coverage expressional differences innexins fmrfamide molluscan insulin peptide genes validated realtime qpcr lastly transcriptomic analyses revealed distinct agespecific gene clusters differentially expressed genes enriched pathways young adult old cns specifically data show significant changes expression critical genes involved transcription factors metabolisms eg cytochrome p450 extracellular matrix constituent signaling receptor transduction eg receptors acetylcholine nmethyldaspartic acid serotonin well stress diseaserelated genes young compared either adult old snailsconclusionstogether datasets largest updated l stagnalis cns transcriptomes will serve resource future molecular studies functional annotation transcripts genes l stagnalis,0.0
dosing schedules ofatumumab multiple sclerosis overegging pudding one therapeutic targets bcell malignancies cd20 transmembrane cellular protein expressed 95 bcell lymphocytes first subcutaneous selfadministered cd20 depleting therapy relapsing forms multiple sclerosis rms ofatumumab kesimpta approved fda august 2020 immunoglobulin class g1 kappa monoclonal antibody mab selectively binds epitope cd20 prior approval subcutaneous form kesimpta iv administered form arzerra ofatumumab fdaapproved patients untreated chronic lymphocytic leukemia cll october 2009,0.0
case report osteomalacia due bisphosphonate treatment patient hemodialysis background publications reported osteomalacia patients receiving intermittent cyclical therapy etidronate bisphosphonate undergoing longterm hemodialysis hd case presentationwe report 46yearold japanese man admitted hospital examination left forearm pain maintenance hd started age 24 years man hd since age 38 years surgical parathyroidectomy performed secondary hyperparathyroidism iliac crest bone biopsy performed time showed osteitis fibrosa active vitamin d3 preparation calcitriol started intermittent cyclical etidronate therapy introduced 2 years later osteoporosis age 45 years patient stopped taking calcitriol hypercalcemia continued etidronate age 46 years pseudofracture looser zone occurred left ulna left femur bone biopsy revealed osteomalacia etidronate discontinued calcitriol restarted open reduction internal fixation angular stability plate performed union bone achieved 10 months operation age 49 years lumber bone biopsy confirmed improved bone morphometryconclusionswe believe intermittent cyclical etidronate therapy without administration active vitamin d3 longterm hd might induced osteomalacia resulting ulna insufficiency fracture therefore propose administration active vitamin d3 essential prevent osteomalacia patients longterm hd receiving bisphosphonates potential vitamin d3 deficiency,0.0
quantitative 7tesla imaging cortical myelin changes early multiple sclerosis front neurol 2021 sep 3 12714820 doi 103389 fneur2021714820 ecollection 2021abstractcortical demyelination occurs early multiple sclerosis ms relates disease outcome brain cortex endogenous propensity remyelination proven histopathology study study aimed characterizing cortical microstructural abnormalities related myelin content applying novel quantitative mri technique early ms combined myelin estimation cme cortical map obtained quantitative 7tesla 7t t 2 t1 acquisitions 25 patients early ms 19 healthy volunteers cortical lesions ms patients classified based myelin content comparison cme values healthy controls demyelinated partially demyelinated nondemyelinated followup registered changes cortical lesions increased decreased stable cme vertexwise analysis compared cortical cme normalappearing cortex 25 ms patients vs 19 healthy controls baseline investigated longitudinal changes 1 year 10 ms patients measurements neurite orientation dispersion density imaging noddi diffusion model obtained account cortical neurite dendrite loss baseline followup finally cme maps correlated clinical metrics cme overall low cortical lesions p 003 several normalappearing cortical areas p 005 absence noddi abnormalities individual cortical lesion analysis revealed however heterogeneous cme patterns extensive partial absent demyelination followup cme overall decreased cortical lesions nonlesioned cortex areas showing increase p 005 cortical cme maps correlated processing speed several areas across cortex conclusion cme allows detection cortical microstructural changes related coexisting demyelination remyelination since early phases ms shows sensitive noddi relates cognitive performancepmid34539559 pmcpmc8446537 doi103389 fneur2021714820,1.0
identification traumatic bone marrow oedema pearls pitfalls dualenergy ct dect tomography 2021 sep 3 7 3 424433 doi 103390 tomography7030037abstractdualenergy computed tomography dect reported successfully identify bone marrow oedema bme various traumatic settings dect multiple strengths including availability 3d view anatomical area studied highresolution dual energy specific maps superimposed onto conventional grayscale morphological images windowing can used enhance visualization bme increasing level superimposed images conversely decreasing level superimposition colorcoded images possible progressively enhance visualization fine anatomical details useful diagnosing associated imaging findings importantly bone sclerosis may represent important pitfall dect potentially generating false positive false negative findings locally altering ct numbers aim paper evaluate strengths limitations dect accurately detecting traumatic bme considering practical approaches imaging several anatomical sitespmid34564299 doi103390 tomography7030037,0.0
novel approaches intervene gut microbiota treatment chronic liver diseases abstractrecent investigations gut microbiota contributed understanding critical role microbial community pathophysiology dysbiosis causes disturbance directly gastrointestinal tract also affects liver gutliver axis various types dysbiosis documented alcoholic liver disease ald nonalcoholic fatty liver disease autoimmune hepatitis aih primary sclerosing cholangitis may crucial initiation progression deterioration endstage liver disease microbial species identified causal factors leading chronic illnesses either clear etiologies lack effective treatment notably cytolysinproducing enterococcus faecalis klebsiella pneumoniae enterococcus gallinarum defined ald nash aih respectively groundbreaking discoveries drive rapid development innovative therapeutics fecal microbial transplantation implementation specific bacteriophages addition prebiotics probiotics synbiotics intervention dysbiosis although emerging interventions preclinical development early clinical trials better delineation specific dysbiosis disorders metabolic immunogenic molecular levels establishing particular causal effects aids modulating correcting microbial community part daily life human,0.0
novel foveal features associated vision impairment multiple sclerosis invest ophthalmol vis sci 2021 sep 2 62 12 27 doi 101167 iovs621227abstractpurpose characterize scattering hyperreflective features foveal avascular zone people multiple sclerosis ms using adaptive optics scanning laser ophthalmoscopy aoslo evaluate relationship visual function ms disease characteristicsmethods twenty subjects ms underwent confocal reflectance nonconfocal splitdetection aoslo foveal imaging peripapillary retinal nerve fiber layer thickness measured using optic nerve optical coherence tomography blood pressure intraocular pressure iop bestcorrected highcontrast visual acuity hcva lowcontrast visual acuity lcva measured aoslo images graded determine presence characteristics distinct structuresresults two distinct structures seen avascular zone foveal pit hyperreflective puncta present 74 eyes associated iop blood pressure scattering features observed 58 eyes associated decreased hcva lcva well increased ms duration disability associated retinal nerve fiber layer thickness hyperreflective puncta scattering features simultaneously present 53 eyesconclusions hyperreflective puncta associated parameters affecting ophthalmic perfusion associated ms disease parameters scattering features associated parameters corresponding advanced ms suggesting may related disease progression scattering features also correlated reduced visual function independent ganglion cell injury suggesting possibility novel ganglion cellindependent mechanism impaired vision people mspmid34581726 doi101167 iovs621227,0.0
increased prevalence familial autoimmune disease children opsoclonusmyoclonus syndrome neurol neuroimmunol neuroinflamm 2021 sep 2 8 6 e1079 doi 101212 nxi0000000000001079 print 2021 novabstractbackground objectives opsoclonusmyoclonus syndrome oms rare autoimmune disorder associated neuroblastoma children although idiopathic postinfectious etiologies present children adults small cohort studies homogenous populations revealed elevated rates autoimmunity family members patients oms although differentiation paraneoplastic nonparaneoplastic forms performed objective study investigate prevalence autoimmune disease firstdegree relatives pediatric patients paraneoplastic nonparaneoplastic omsmethods singlecenter cohort study consecutively evaluated children oms performed parents patients prospectively administered surveys familial autoimmune disease rates autoimmune disease firstdegree relatives pediatric patients oms compared using fisher exact t test 2 analysis 1 without paraneoplastic cause 2 healthy disease pediatric multiple sclerosis ms controls united states pediatric ms networkresults thirtyfive patients 18 paraneoplastic median age onset 190 months 17 idiopathic median age onset 250 months 68 firstdegree relatives median age 419 years enrolled one patient developed systemic lupus erythematosus 7 years oms onset paraneoplastic oms associated 50 rate autoimmune disease firstdegree relative compared 29 idiopathic oms p 031 rate firstdegree relative autoimmune disease per oms case 14 35 40 higher healthy controls 86 709 12 p 0001 children pediatric ms 101 495 20 p 0007 discussion cohort pediatric patients oms elevated rates firstdegree relative autoimmune disease difference rates observed paraneoplastic idiopathic etiologies suggesting autoimmune genetic contribution development oms childrenpmid34475249 doi101212 nxi0000000000001079,0.0
aktmtor pathway drives myelin sheath growth regulating capdependent translation vertebrate central nervous system oligodendrocytes produce myelin specialized membrane insulate support axons individual oligodendrocytes wrap multiple axons myelin sheaths variable lengths thicknesses myelin grows distal ends oligodendrocyte processes multiple lines work provided evidence mrnas rna binding proteins localize myelin together supporting model local translation controls myelin sheath growth signal transduction mechanisms control one strong candidate aktmtor pathway major cellular signaling hub coordinates transcription translation metabolism cytoskeletal organization using zebrafish model system found aktmtor signaling promotes myelin sheath growth stability development cellspecific manipulations oligodendrocytes show aktmtor pathway drives capdependent translation promote myelination restoration capdependent translation sufficient rescue myelin deficits mtor lossoffunction animals moreover mtordependent translational regulator phosphorylated colocalized mrna encoding canonically myelintranslated protein vivo bioinformatic investigation revealed numerous putative translational targets myelin transcriptome together data raise possibility aktmtor signaling nascent myelin sheaths promotes sheath growth via translation myelinresident mrnas development,1.0
pain cognition disability advanced multiple sclerosis scand j pain 2021 sep 2 doi 101515 sjpain20210067 online ahead printabstractobjectives patients multiple sclerosis ms relationship physical disability pain observed addition relationship physical disability cognition ms suggested however cognitive functions pain appear correlated ms patients therefore examined whether possible relationship pain cognitive functioning may exist relationship mediated physical disabilitymethods fortyfive ms patients chronic pain advanced stage disease included physical disabilities assessed expanded disability status scale edss episodic memory assessed means eight words test face picture recognition executive functions ef examined digit span backward working memory rule shift cards category fluency test cognitive flexibility pain intensity pain affect assessed means visual analogue scales one verbal pain scale mood depression anxiety beck depression inventory symptom check list scl90 research questions analyzed means regression analyses sobel test mediationresults significant relationship found pain affect ef relationship mediated physical disabilities edss addition pain intensity ef showed significant relationship combination physical disabilities edss finally mood related pain affectdiscussion findings suggest lower ef exclusively combination physical disabilities patient may suffer painimplications one cognitively physically impaired one might suffer pain less one able communicate pain latter put ms patients risk underdiagnosing undertreatment painpmid34469640 doi101515 sjpain20210067,0.0
intrathecal baclofen therapy severe spasticity adult tethered cord syndrome case report background patients tethered cord syndrome often suffer severe spasticity best knowledge intrathecal baclofen itb therapy patient tethered cord syndrome reported previously describe case itb therapy useful treating severe spasticity adult tethered cord syndromecase presentationwe present case 50yearold japanese woman tethered cord syndrome related conditions suffering severe spasticity pain lower limbs born lumbosacral myelomeningocele closed neonatal period 45 years presentation spasticity lower limbs exacerbated without obvious cause received rehabilitation pharmacotherapy local doctor symptoms unimproved previous doctor referred department test 50 g intrathecally delivered baclofen showed total relief spasticity pain pump implanted continuous baclofen delivery 24 months followup spasticity remained excellent control baclofen 385410 g dayconclusionsitb therapy proved extremely effective adult severe spasticity tethered code syndrome,0.0
breast carcinoma ocrelizumab therapy multiple sclerosis patients case series literature review j cent nerv syst dis 2021 sep 2 1311795735211037785 doi 101177 11795735211037785 ecollection 2021abstractocrelizumab humanized cd20 monoclonal antibody approved management relapsing remitting multiple sclerosis rrms primary progressive multiple sclerosis ppms 2017 present 2 patients 67yearold woman history ppms 42yearold woman rrms started ocrelizumab diagnosed invasive ductal cell breast carcinoma 2 years ocrelizumab infusion followed discontinuation drug large trials conducted ocrelizumab showed malignancies total 4 cases rrms opera 1 trial conducted 2 years 2011 2013 breast cancer renal cell carcinoma melanomas 11 cases ppms seen oratorio trial conducted 2017 currently published case reports breast cancer setting ocrelizumab use ms outside large trials literature reviewpmid34497472 pmcpmc8419566 doi101177 11795735211037785,0.0
longterm safety efficacy dimethyl fumarate 13years patients relapsingremitting multiple sclerosis final endorse study results backgrounddimethyl fumarate dmf demonstrated favorable benefitrisk relapsingremitting multiple sclerosis rrms patients phaseiii define confirm trials endorse extensionobjectivethe main aim study assessing dmf safety efficacy 13years endorsemethodsrandomized patients received dmf 240 mg twice daily placebo pbo years 02 dmf years 310 continuous dmf dmf pbo dmf maximum followup combined studies 13yearsresultsby january 2020 1736 patients enrolled dosed endorse median followup 876years endorse range 0041098 define confirm endorse 52 treated endorse 6years overall 551 32 patients experienced serious adverse events mostly multiple sclerosis ms relapse fall one progressive multifocal leukoencephalopathy 243 14 discontinued treatment due adverse events 4 gastrointestinal gi disorders rare opportunistic infections malignancies serious herpes zoster occurred irrespective lymphocyte count dmf dmf n 501 overall annualized relapse rate arr remained low 0143 95 confidence interval ci 01200169 pbo dmf n 249 arr decreased initiating dmf remained low throughout arr 02years 0330 95 ci 02660408 overall arr endorse 0151 95 ci 01180194 10years 72 dmf dmf 73 pbo dmf 24week confirmed disability worseningconclusionsustained dmf safety efficacy observed patients followed 13years supporting dmfs positive benefit risk profile longterm rrms treatment,1.0
vaccine hesitancy among people multiple sclerosis abstractbackgroundthe current severe acute respiratory syndromecoronavirus2 sarscov2 pandemic raised awareness vaccine hesitancy specific reasons vaccine hesitancy among people multiple sclerosis pwms fully described notably pwms may experience higher morbidity vaccinepreventable diseases influenza pneumococcal disease human papillomavirus hpv associated warts malignancies furthermore screening immunity measles mumps rubella mmr standard practice despite resurgence measles mumps outbreaks europe worldwide aimed evaluate general vaccination status among pwms better inform vaccine practices cohortmethodsthis prospective audit pwms attending irish tertiary referral ms centre designed questionnaire explored awareness uptake hesitancy influenza pneumococcal sarscov2 hpv mmr vaccines clinician administered questionnaire outpatient ms clinicresultsonehundredandfive pwms participated audit mean sd age 473 128 years mean ms disease duration 141 95 years median expanded disability severity scale edss score 20 iqr 1060 fortynine 467 taking either maintenance immunosuppressive immune reconstitution therapies sarscov2 vaccine willingness among pwms higher 905 vs 6080 reported western countries higher influenza pneumococcal vaccines 80 perceived unnecessity unfamiliarity respectively main limiting factors primary reason sarscov2 vaccine hesitancy safety concern pwms explicitly advised healthcare professional obtain influenza vaccine likely odds ratio 81 95 ci 28 234 p0001 pwms currently receiving bcell therapy ocrelizumab rituximab n12 one n11 917 never received pneumococcal vaccine quarter n3 uncertain whether obtain future patientreported uptake hpv 10 mmr 514 vaccines suboptimal prevalence vaccine promotion among healthcare professionals low influenza vaccine 48 324 pneumococcal vaccine 0 181 conclusionsvaccine hesitancy common 1020 pwms consequent insufficient knowledge misconceptions vaccination among pwms suboptimal vaccine promotion healthcare professionals manage pwms conscientious contextspecific vaccination counselling necessary tackle vaccine hesitancy among pwms including avoiding infectionassociated disability accrual ms relapses ii reducing potentially higher risk lifethreatening treatmentrefractory complications may observed develop vaccinepreventable infections receiving certain dmts iii avoiding attenuated vaccine responses delayed interrupted dmt early pretreatment vaccine delivery possible,0.0
identification gliogenic state human neural stem cells optimize vitro astrocyte differentiation j neurosci methods 2021 jul 6109284 doi 101016 jjneumeth2021109284 online ahead printabstractbackground human preclinical models crucial advancing biomedical research particular consistent robust protocols astrocyte differentiation human system rarenew method performed transcriptional characterization human gliogenesis using embryonic h9 derived hnscs based findings established fast highly efficient protocol differentiation mature human astrocytes reproduce results induced pluripotent stem cell ipsc derived nscsresults identified increasing propensity nscs give rise astrocytes repeated cell passaging gliogenic phenotype nscs marked downregulation stem cell factors eg sox1 sox2 egfr increase gliaassociated factors eg nfix sox9 pdgfra using late passage nscs rapid robust astrocyte differentiation can achieved within 28 dayscomparison existing method s published protocols usually takes around three months yield mature astrocytes difficulty expense time associated generating astrocytes vitro represents major roadblock glial cell research show rapid robust astrocyte differentiation can achieved within 28 days describe extensive sequential transcriptome analysis hnscs characterization signature novel gliogenic stem cell population transcriptomic signature might serve identify proper divisional maturityconclusions work sheds light factors associated rapid nsc differentiation glial cells findings contribute understand human gliogenesis develop novel preclinical models will help study cns disease multiple sclerosispmid34242705 doi101016 jjneumeth2021109284,0.0
effects behavioural therapy versus interferential current bladder dysfunction multiple sclerosis patients randomised clinical study j taibah univ med sci 2021 sep 1 16 6 812818 doi 101016 jjtumed202108003 ecollection 2021 decabstractobjectives study examines effect behavioural therapy biofeedback interferential current bladder dysfunction multiple sclerosis patientsmethods fifty patients secondary progressive type multiple sclerosis spms suffering bladder dysfunction divided equally two groups randomly group ga received behavioural therapy biofeedback training group b gb received interferential current training groups assessed urodynamics detrusor pressure maximum flow rate eight weeks behavioural therapy interferential trainingresults groups ga gb showed significant increase detrusor pressure maximum flow rate eight weeks training significant difference methods however ga showed improvement close observationconclusions behavioural therapy interferential current training effectively managed bladder dysfunction patients spms evident effects behavioural therapy patients close observationpmid34899124 pmcpmc8626809 doi101016 jjtumed202108003,0.0
myelinoligodendrocyte glycoprotein antibodyassociated disease summarymyelinoligodendrocyte glycoprotein antibodyassociated disease mogad recently identified autoimmune disorder presents adults children cns demyelination although clinical phenotypic overlaps mogad multiple sclerosis aquaporin4 antibodyassociated neuromyelitis optica spectrum disorder nmosd cumulative biological clinical pathological evidence discriminates conditions patients diagnosed multiple sclerosis nmosd antimog antibodies serum however many questions related clinical characterisation mogad pathogenetic role mog antibodies still unanswered furthermore therapy mainly based standard protocols aquaporin4 antibodyassociated nmosd multiple sclerosis evidence needed regarding treat patients mogad,1.0
treatment central disorders hypersomnolence american academy sleep medicine clinical practice guideline j clin sleep med 2021 sep 1 17 9 18811893 doi 105664 jcsm9328abstractintroduction guideline establishes clinical practice recommendations treatment central disorders hypersomnolence adults childrenmethods american academy sleep medicine commissioned task force experts sleep medicine develop recommendations assign strengths recommendation based systematic review literature assessment evidence using grade process task force provided summary relevant literature quality evidence balance benefits harms patient values preferences resource use considerations support recommendations aasm board directors approved final recommendationsrecommendations following recommendations intended guide clinicians choosing specific treatment central disorders hypersomnolence adults children recommendation statement assigned strength strong conditional strong recommendation ie recommend one clinicians follow circumstances conditional recommendation ie suggest one requires clinician use clinical knowledge experience strongly consider individual patients values preferences determine best course action disorder strong recommendations listed alphabetical order followed conditional recommendations alphabetical order section adult patients hypersomnia medical conditions categorized based clinical pathological subtypes identified icsd3 interventions recommendation statements compared treatment1 recommend clinicians use modafinil treatment narcolepsy adults strong 2 recommend clinicians use pitolisant treatment narcolepsy adults strong 3 recommend clinicians use sodium oxybate treatment narcolepsy adults strong 4 recommend clinicians use solriamfetol treatment narcolepsy adults strong 5 suggest clinicians use armodafinil treatment narcolepsy adults conditional 6 suggest clinicians use dextroamphetamine treatment narcolepsy adults conditional 7 suggest clinicians use methylphenidate treatment narcolepsy adults conditional 8 recommend clinicians use modafinil treatment idiopathic hypersomnia adults strong 9 suggest clinicians use clarithromycin treatment idiopathic hypersomnia adults conditional 10 suggest clinicians use methylphenidate treatment idiopathic hypersomnia adults conditional 11 suggest clinicians use pitolisant treatment idiopathic hypersomnia adults conditional 12 suggest clinicians use sodium oxybate treatment idiopathic hypersomnia adults conditional 13 suggest clinicians use lithium treatment kleinelevin syndrome adults conditional 14 suggest clinicians use armodafinil treatment hypersomnia secondary dementia lewy bodies adults conditional 15 suggest clinicians use modafinil treatment hypersomnia secondary parkinsons disease adults conditional 16 suggest clinicians use sodium oxybate treatment hypersomnia secondary parkinsons disease adults conditional 17 suggest clinicians use armodafinil treatment hypersomnia secondary traumatic brain injury adults conditional 18 suggest clinicians use modafinil treatment hypersomnia secondary traumatic brain injury adults conditional 19 suggest clinicians use modafinil treatment hypersomnia secondary myotonic dystrophy adults conditional 20 suggest clinicians use modafinil treatment hypersomnia secondary multiple sclerosis adults conditional 21 suggest clinicians use modafinil treatment narcolepsy pediatric patients conditional 22 suggest clinicians use sodium oxybate treatment narcolepsy pediatric patients conditional citation maski k trotti lm kotagal s et al treatment central disorders hypersomnolence american academy sleep medicine clinical practice guideline j clin sleep med 2021 17 9 18811893pmid34743789 doi105664 jcsm9328,0.0
impact hypoxia bloodbrain bloodcsf csfbrain barriers j appl physiol 1985 2021 jul 15 doi 101152 japplphysiol001082020 online ahead printabstractthe bloodbrain barrier bbb bloodcerebrospinal fluid barrier bcsfb csfbrain barriers csfbb highly regulated barriers central nervous system comprising complex multicellular structures separate nerves glia blood cerebrospinal fluid respectively barrier damage implicated pathophysiology diverse hypoxiarelated neurological conditions including stroke multiple sclerosis hydrocephalus highaltitude cerebral edema much known damage bbb response hypoxia much less known bcsfb csfbb yet known barriers implicated damage hypoxia inflammation 1950s shown rate radionucleated human serum albumin passage plasma csf 5times higher hypoxic normoxic conditions dogs due bloodcsf barrier disruption severe hypoxia due administration bacterial toxin lipopolysaccharide lps associated disruption csfbb review discusses anatomy bbb bcsfb csfbb impact hypoxia associated inflammation regulation barrierspmid34264124 doi101152 japplphysiol001082020,0.0
impact lower limb immobilization rehabilitation angiogenic proteins capillarization skeletal muscle med sci sports exerc 2021 mar 25 doi 101249 mss0000000000002665 online ahead printabstractpurpose skeletal muscle vascularization important tissue regeneration injury immobilization examined whether complete immobilization influences capillarization oxygen delivery muscle assessed efficacy rehabilitation aerobic exercise trainingmethods young healthy males one leg immobilized 14 days subsequently completed four weeks intense aerobic exercise training biopsies obtained mvastus lateralis av blood sampling assessment oxygen extraction leg blood flow exercise done immobilization training muscle capillarization muscle platelet content vascular endothelial growth factor vegf muscle thrombospondin1 determinedresults immobilization significant impact capillary per fiber ratio capillary density content vegf protein muscle samples reduced 36 p0024 vegf thrombospondin1 ratio 94 lower p0046 subsequent fourweek training period increased muscle vegf content normalized muscle vegf thrombospondin1 ratio influence capillarization platelet vegf content followed trend muscle vegf functional level oxygen extraction blood flow oxygen delivery rest submaximal exercise affected immobilization trainingconclusion results demonstrate just two weeks leg immobilization leads strongly reduced angiogenic potential evidenced reduced muscle platelet vegf content reduced muscle vegf thrombospondin1 ratio moreover subsequent period intensive aerobic exercise training fails increase capillarization previously immobilized leg possibly due angiostatic condition caused immobilizationpmid33787530 doi101249 mss0000000000002665,0.0
central vestibular functions correlate fatigue walking capacity people multiple sclerosis phys ther 2021 jun 25pzab168 doi 101093 ptj pzab168 online ahead printabstractobjective imbalance fatigue among common disabling symptoms multiple sclerosis ms vestibular rehabilitation studies demonstrate improvements balance fatigue also suggesting relationship central vestibular integration fatigue objective study determine whether relationship balance fatigue people ms seen measures central vestibular integration fatigue understand central vestibular integration measures interrelatemethods crosssectional study consisted 40 people ms ages 2755 years expanded disability severity scale score 1065 completed vestibular ocular reflex testing subjective visual vertical testing static posturography dynamic gait 2 selfreport fatigue surveys 6minute walk test assess walking capacity physical fatigue completed spearman correlations calculated variablesresults measures central vestibular integration significantly correlated measures fatigue walking capacity correlations physical fatigue central vestibular functions larger selfreported fatigue correlations central vestibular functionsconclusion relationship balance fatigue extends measures requiring central vestibular integration suggesting deficit central vestibular processing people ms measures may compliment balance assessment outcome measures vestibular rehabilitation people ms fatigue measures included vestibular rehabilitation secondary outcomesimpact correlations central vestibular integration fatigue people ms suggest future studies vestibular rehabilitation include fatigue secondary outcome measure vestibular function fatigue may share similar similar etiology people mspmid34174079 doi101093 ptj pzab168,1.0
automatic segmentation gadoliniumenhancing lesions multiple sclerosis using deep learning clinical mri plos one 2021 sep 1 16 9 e0255939 doi 101371 journalpone0255939 ecollection 2021abstractgadoliniumenhancing lesions reflect active disease critical inpatient monitoring multiple sclerosis ms work developed first fully automated method segment count gadoliniumenhancing lesions routine clinical mri ms patients proposed method first segments potential lesions using 2dunet multichannel scans t1 postcontrast t1 precontrast flair t2 protondensity classifies lesions using random forest classifier algorithm trained validated 600 mris manual segmentation compared effect loss functions dice cross entropy bootstrapping cross entropy number input contrasts compared lesion counts radiologists using 2 846 images dice lesionwise sensitivity false discovery rate full 5 contrasts 0698 0844 0307 improved 0767 0969 000 large lesions 100 voxels model using bootstrapping loss function provided statistically significant increase 71 sensitivity 23 dice compared model using cross entropy loss t1 post precontrast flair important contrasts large lesions 2dunet model trained using t1 precontrast flair t2 pd lesionwise sensitivity 0688 false discovery rate 0083 even without t1 postcontrast counting lesions 2846 routine mri images model 2dunet random forest trained bootstrapping cross entropy achieved accuracy 877 using t1 precontrast t1 postcontrast flair lesion counts categorized 0 1 2 model performs well routine nonstandardized mri datasets allows largescale analysis clinical datasets may clinical applicationspmid34469432 doi101371 journalpone0255939,0.0
treatment central disorders hypersomnolence american academy sleep medicine systematic review metaanalysis grade assessment j clin sleep med 2021 sep 1 17 9 18951945 doi 105664 jcsm9326abstractintroduction systematic review provides supporting evidence accompanying clinical practice guideline treatment central disorders hypersomnolence adults children review focuses prescription medications us food drug administration approval nonpharmacologic interventions studied treatment symptoms caused central disorders hypersomnolencemethods american academy sleep medicine commissioned task force experts sleep medicine perform systematic review randomized controlled trials observational studies addressing pharmacological nonpharmacological interventions central disorders hypersomnolence identified statistical analyses performed determine clinical significance outcomes finally grading recommendations assessment development evaluation grade process used assess evidence purpose making specific treatment recommendationsresults literature search identified 678 studies 144 met inclusion criteria 108 provided data suitable statistical analyses evidence following interventions presented armodafinil clarithromycin clomipramine dextroamphetamine flumazenil intravenous immune globulin ivig light therapy lithium lcarnitine liraglutide methylphenidate methylprednisolone modafinil naps pitolisant selegiline sodium oxybate solriamfetol triazolam task force provided detailed summary evidence along quality evidence balance benefits harms patient values preferences resource use considerationscitation maski k trotti lm kotagal s et al treatment central disorders hypersomnolence american academy sleep medicine systematic review metaanalysis grade assessment j clin sleep med 2021 17 9 18951945pmid34743790 doi105664 jcsm9326,0.0
btk inhibitors potential therapies multiple sclerosis past 30 years increasing numbers molecules developed treatment multiple sclerosis however given heterogeneity disease fact many patients refractory progressive multiple sclerosis new therapeutic alternatives still needed tyrosine kinases enzymes mediate phosphorylation tyrosine residues downstream molecules participate signalling pathways kinases crucial roles cellular proliferation differentiation cell growth metabolism survival apoptosis making potential therapeutic targets various autoimmune lymphoproliferative diseases 1 2 brutons tyrosine kinase cytoplasmic tyrosine kinase expressed b cells myeloid cells 3 b cells myeloid cells particularly microglia important drivers multiple sclerosis 4 suggesting inhibitors brutons tyrosine kinase irreversible inhibitors evobrutinib tolebrutininb orelabrutinib reversible inhibitors fenebrutinib biib091 might provide therapeutic benefits patients,1.0
safety efficacy tolebrutinib oral brainpenetrant btk inhibitor relapsing multiple sclerosis phase 2b randomised doubleblind placebocontrolled trial summarybackgroundtolebrutinib oral cnspenetrant irreversible inhibitor brutonnulls tyrosine kinase enzyme expressed b lymphocytes myeloid cells including microglia major drivers inflammation multiple sclerosis aimed determine doseresponse relationship tolebrutinib reduction new active brain mri lesions patients relapsing multiple sclerosismethodswe 16week phase 2b randomised doubleblind placebocontrolled crossover dosefinding trial 40 centres academic sites specialty clinics general neurology centres ten countries europe north america eligible participants adults aged 1855 years diagnosed relapsing multiple sclerosis either relapsingremitting relapsing secondary progressive multiple sclerosis one following criteria least one relapse within previous year least two relapses within previous 2 years least one active gadoliniumenhancing brain lesion 6 months screening exclusion criteria included diagnosis primary progressive multiple sclerosis diagnosis secondary progressive multiple sclerosis without relapse used twostep randomisation process randomly assign eligible participants 11 two cohorts randomly assign participants cohort 1111 four tolebrutinib dose groups 5 15 30 60 mg administered daily oral tablet cohort 1 received tolebrutinib 12 weeks matched placebo ie identical looking tablets 4 weeks cohort 2 received 4 weeks placebo followed 12 weeks tolebrutinib participants investigators masked dose tolebrutinibplacebo administration sequence investigators study team members study participants access unmasked data mri scans done screening every 4 weeks 16 weeks primary efficacy endpoint number new gadoliniumenhancing lesions detected scan done 12 weeks tolebrutinib treatment assessed week 12 cohort 1 week 16 cohort 2 relative scan done 4 weeks previously compared lesions accumulated 4 weeks placebo runin period cohort 2 efficacy data analysed modified intentiontotreat population using twostep multiple comparison procedure modelling analysis safety assessed participants received least one dose study drug trial registered clinicaltrialsgov nct03889639 eudract 201800392712 u111112200572 completedfindingsbetween may 14 2019 jan 2 2020 enrolled randomly assigned 130 participants tolebrutinib 33 5 mg 32 15 mg 33 30 mg 32 60 mg 129 99 completed treatment regimen 126 included primary analysis treatment week 12 dosedependent reduction number new gadoliniumenhancing lesions mean sd lesions per patient placebo 103 250 5 mg 139 320 15 mg 077 148 30 mg 076 331 60 mg 013 043 p003 one serious adverse event reported one patient 60 mg group admitted hospital multiple sclerosis relapse common nonserious adverse event tolebrutinib treatment headache one 3 33 5 mg group three 9 32 15 mg group one 3 33 30 mg group four 13 32 60 mg group safetyrelated discontinuations treatmentrelated deaths occurredinterpretation12 weeks tolebrutinib treatment led dosedependent reduction new gadoliniumenhancing lesions 60 mg dose efficacious drug well tolerated reduction acute inflammation combined potential modulate immune response within cns provides scientific rationale pursue phase 3 clinical trials tolebrutinib patients relapsing progressive forms multiple sclerosisfundingsanofi,1.0
nanoinmicroparticles consisting plga nanoparticles embedded chitosan microparticles via spraydrying enhances uptake olfactory mucosa front pharmacol 2021 sep 1 12732954 doi 103389 fphar2021732954 ecollection 2021abstractintranasal delivery gained prominence since 1990 olfactory mucosa recognized window brain central nervous system cns enabled direct site specific targeting neurological diseases first time intranasal delivery promising route general limitations bloodbrain barrier bbb circumvented treatment multiple sclerosis ms alzheimers disease example future treatment prospects include specialized particles delivery vehicles poly lacticcoglycolic acid plga nanoparticles well known promising delivery systems especially area nosetobrain n2b delivery chitosan also broadly known functional additive due ability open tight junctions study produced plga nanoparticles different sizes revealed first time sizetimedependent uptake mechanism lamina propria porcine olfactory mucosa intracellular uptake observed 80 175 nm within 5 min application epithelium 15 min even 520 nm particles detected associated nuclei especially presence 520 nm particles neuronal fibers remarkable implying transcellular intracellular transport via olfactory trigeminal nerve brain cns additionally developed successfully specialized nanoinmicro particles nimps first time via spray drying consisting plga nanoparticles embedded chitosan microparticles characterized high encapsulation efficiencies 51 reproducible uniform size distribution well smooth surface application nimps accelerated uptake compared purely applied plga nanoparticles nimps spread whole transverse section olfactory mucosa within 15 min faster uptake attributed additional paracellular transport examined via tightjunctionopening furthermore separate chitosan penetration gradient 150 m caused dissociation plga nanoparticles observed within 15 min lamina propria demonstrated proportional immunoreactivity gradient cd14 due beneficial properties utilized chitosanderivative regarding molecular weight 150300 kda degree deacetylation 80 particle size 0110 m concluded m2macrophages herein initiated antiinflammatory reaction seems already take place within 15 min following chitosan particle application conclusion demonstrated possibility plga nanoparticles well chitosan nimps take three prominent intranasal delivery pathways brain cns namely transcellular intracellular via neuronal cells paracellular transportpmid34539414 pmcpmc8440808 doi103389 fphar2021732954,0.0
role hyaluronan myelination remyelination white matter injury brain res 2021 may 16147522 doi 101016 jbrainres2021147522 online ahead printabstracthyaluronan one major components neural extracellular matrix ecm provides structural support physiological conditions altered hyaluronan regulation implicated pathogenesis white matter injury wmi perinatal wmi multiple sclerosis ms traumatic brain injury tbi early research reported diverse central nervous system cns insults led accumulated highmolecularweight hmw hyaluronan hypomyelinating demyelinating lesions furthermore recent findings shown elevated production hyaluronan fragments wmi possibly resulting hmw hyaluronan degradation subsequent vitro studies identified bioactive hyaluronan fragments specific molecular weight around 2x105 da regulating oligodendrocyte precursor cells opcs maturation myelination remyelination wmi however unclear effective hyaluronidases generating bioactive hyaluronan fragments several hyaluronidases proposed recently although ph20 shown block opcs maturation generating bioactive hyaluronan fragments vitro seems unlikely play primary role wmi negligible expression levels vivo role hyaluronidases opcs maturation myelination remyelination still unknown hyaluronidases cd44 tolllike receptors 2 tlr2 also implicated hmw hyaluronan degradation wmi moreover recent studies elucidated bioactive hyaluronan fragments interact tlr4 initiating signaling cascades mediate myelin basic protein mbp transcription identifying key factors hyaluronan actions may provide novel therapeutic targets promote opcs maturation myelination remyelination wmipmid34010609 doi101016 jbrainres2021147522,1.0
mediastinal lymphoproliferative disorders adv anat pathol 2021 jun 2 doi 101097 pap0000000000000305 online ahead printabstractlymphoproliferative disorders comprise 50 60 mediastinal malignancies children adults primary mediastinal involvement rare 5 whereas secondary mediastinal involvement systemic disease common 10 25 primary mediastinal disease defined involvement lymphoproliferative disorder mediastinal lymph nodes thymus extranodal mediastinal organs without evidence systemic disease presentation review clinical radiologic histopathologic immunohistochemical genetic features characteristic mediastinal lymphoproliferative disorders presented entities discussed include classic hodgkin lymphoma emphasis nodular sclerosis mixed cellularity types nonhodgkin lymphomas including primary mediastinal thymic large bcell lymphoma mediastinal gray zone lymphoma mediastinal diffuse large bcell lymphoma thymic marginal zone lymphoma mediastinal plasmacytoma tlymphoblastic lymphoma anaplastic large cell lymphoma although malignant process hyaline vascular castleman disease also discussed disorder commonly involves mediastinum despite multiple advances hematopathology recent decades daytoday diagnosis lesions still requires morphologic approach proper selection immunohistochemical markers reason crucial general pathologists familiar entities particular clinicoradiologic presentationpmid34074861 doi101097 pap0000000000000305,0.0
predictive factors diagnostic therapeutic divergence nationwide cohort patients seeking second medical opinion abstractobjectivesthe aim study describe profile patients sought second medical opinion smo therapeutic diagnostic strategy using nationwide data french physician network dedicated smosmethodsan observational cohort study conducted study population consisted patients residing france french overseas territories submitted request smo dedicated platform january 2016 october 2020 patient characteristics compared convergent divergent smos divergent rate patients excluding mental diseases described logistic regression used estimate probability divergent smo according patient characteristicsresults discussionin total 1 552 adult patients several french regions included divergence rate 323 n 502 patients gynecological odds ratio 95 ci 5176 3154 8494 urological 4246 2053 8782 respiratory diseases 3639 1357 9758 highest probability divergent smo complex cases also associated significantly higher risk divergent opinion 278 216 359 age sex region profession found predictive divergent second opinionconclusionspolicymakers encourage new research patient outcomes mortality hospitalization rates smo proven effective smo networks will potential benefit specific public funding even play key role national healthcare quality improvement programs,0.0
dimethyl fumarate experience handy drug broad clinical utility front neurol 2021 sep 1 12679355 doi 103389 fneur2021679355 ecollection 2021abstractobjectives aim study characterize multiple sclerosis ms patients exposed dimethyl fumarate dmf evaluate predictors therapeutic response addition study offers picture dmf use changed past years naive switcher patients methods observational monocentric study examined prescription flow dmf ms patients categorized naive switchers safety tolerability ineffectiveness deescalation strategy 2015 2019 clinical magnetic resonance imaging data dmftreated patients analyzed neda3 status 24 months evaluated three assessment components absence clinical relapses expanded disability status scale progression radiological activity determinants therapeutic response also evaluated using regression analysis results sample included 595 ms patients exposed dmf categorized naive 158 265 switchers reasons safety tolerability 198 333 inefficacy 175 294 deescalation strategy 64 108 15 increase dmf use naive horizontal shift groups observed last 3 years observation whereas drop prescription passed 20 5 exit strategy secondline therapies neda3 status calculated 340 patients 24 months dmf treatment achieved 188 553 analyzing predictors dmf response observed lower annualized relapse rate arr 2 years pretreatment hazard ratio hr 049 p 0001 naive patients hr 138 p 0035 associated achievement neda3 analogously arr 2 years pretreatment affected neda3 achievement 24 months patients deescalation group hr 007 p 0041 also indicating effect related dmf initiation within 3 months hr 124 p 0029 conclusion findings confirm dmf handy drug broad clinical utility greater benefits naive patients horizontal switchers additionally increase flow dmf prescriptions two groups patients also observed cohortpmid34539545 pmcpmc8440841 doi103389 fneur2021679355,0.0
clinical monitoring multiple sclerosis patients means digital technology field midst revolution rev neurol 2021 sep 1 73 6 210218 doi 1033588 rn73062021136abstractintroduction despite great advances occurred diagnosis treatment multiple sclerosis ms changes taken place terms clinical monitoring lack time space clinical practice limits assessment invisible symptoms certain motor symptoms manual dexterity walking ability clear impact patient functional situationobjective review potential role technological tools clinical monitoring ms patientsdevelopment bibliographic search carried pubmed selecting studies focused biosensors digital tools aimed evaluating general functional situation specific aspects disease certain functional systemsresults different digital tools biosensors mobile web applications remote hospital use selfcompleted administered healthcare personnel seem offer complete real picture functional situation patients studies shown digital technology detect subclinical disability progression traditional tests including edss fail reflect favouring adoption appropriate therapeutic measures actions early personalized mannerconclusions digital tools capable collecting detailed extensive clinical information play important role decisionmaking clinical monitoring patients mspmid34515334 doi1033588 rn73062021136,0.0
microglianeuron interaction nodes ranvier depends neuronal activity potassium release contributes remyelination nat commun 2021 sep 1 12 1 5219 doi 101038 s41467021254867abstractmicroglia resident immune cells central nervous system key players healthy brain homeostasis plasticity neurological diseases multiple sclerosis activated microglia either promote tissue damage favor neuroprotection myelin regeneration mechanisms microglianeuron communication remain largely unkown identify nodes ranvier direct site interaction microglia axons mouse human tissues using dynamic imaging highlight preferential interaction microglial processes nodes ranvier along myelinated fibers show microglianode interaction modulated neuronal activity associated potassium release thik1 ensuring microglial readout altered axonal k+ flux following demyelination impairs switch towards proregenerative microglia phenotype decreases remyelination rate taken together findings identify node ranvier major site microglianeuron interaction may participate microglianeuron communication mediating proremyelinating effect microglia myelin injurypmid34471138 doi101038 s41467021254867,1.0
safety efficacy bexarotene patients relapsingremitting multiple sclerosis ccmr one randomised doubleblind placebocontrolled parallelgroup phase 2a study summarybackgroundprogressive disability multiple sclerosis occurs cns axons degenerate late consequence demyelination animals retinoic acid receptor rxrgamma agonists promote remyelination aimed assess safety efficacy nonselective retinoid x receptor agonist promoting remyelination people multiple sclerosismethodsthis randomised doubleblind placebocontrolled parallelgroup phase 2a trial ccmr one recruited patients relapsingremitting multiple sclerosis two centres uk eligible participants aged 1850 years receiving dimethyl fumarate least 6 months via webbased system run independent statistician participants randomly assigned 11 probabilityweighted minimisation using four binary factors receive 300 mg m2 body surface area per day oral bexarotene oral placebo 6 months participants investigators outcome assessors masked treatment allocation mri scans done baseline 6 months primary safety outcome number adverse events withdrawals attributable bexarotene primary efficacy outcome patientlevel change mean lesional magnetisation transfer ratio baseline month 6 lesions baseline magnetisation transfer ratio less withinpatient median analysed primary safety outcome safety population comprised participants received least one dose allocated treatment analysed primary efficacy outcome intentiontotreat population comprised patients completed study study registered isrctn registry 14265371 completedfindingsbetween jan 17 2017 may 17 2019 52 participants randomly assigned receive either bexarotene n26 placebo n26 participants received bexarotene higher mean number adverse events 612 sd 309 159 events total participants received placebo 163 sd 150 39 events total bexarotenetreated participants least one adverse event included central hypothyroidism n26 vs none placebo hypertriglyceridaemia n24 vs none placebo rash n13 vs one placebo neutropenia n10 vs none placebo five 19 participants bexarotene two 8 placebo discontinued study drug due adverse events one episode cholecystitis placebotreated participant serious adverse event change mean lesional magnetisation transfer ratio different bexarotene group 025 percentage units pu sd 098 placebo group 009 pu 084 adjusted bexaroteneplacebo difference 016 pu 95 ci 039 071 p055 interpretationwe recommend use bexarotene treat patients multiple sclerosis poor tolerability negative primary efficacy outcome however statistically significant effects seen exploratory mri electrophysiological analyses suggesting retinoid x receptor agonists might small biological effects investigated studiesfundingmultiple sclerosis society united kingdom,1.0
nkt nktlike cells autoimmune neuroinflammatory diseasesmultiple sclerosis myasthenia gravis guillainbarre syndrome int j mol sci 2021 sep 1 22 17 9520 doi 103390 ijms22179520abstractnkt cells comprise three subsetstype invariant inkt type ii nktlike cells inkt cells studied subset capable rapid cytokine production initial stimulus thus may important polarisation th cells due may important cell subset autoimmune diseases current review summarising results nktoriented studies major neurological autoimmune diseasesmultiple sclerosis myasthenia gravis guillainbarre syndrome corresponding animal modelspmid34502425 doi103390 ijms22179520,0.0
quot precision medicine autoimmune diseases fact fictionquot rheumatology oxford 2021 may 18keab448 doi 101093 rheumatology keab448 online ahead printabstractmuch said precision medicine real significance possibility making real possibility far certain several studies autoimmune diseases provided important insight molecular pathways use molecular studies particularly looking transcriptome pathways seldom approached possibility using data disease stratification prediction diagnosis type interferon signature considered use signature therapeutic purposes particularly case systemic lupus erythematosus authors provide update precision medicine can translated clinical practice singlecell molecular studies provide knowledge autoimmune diseases focusing examples main message try move precision medicine established disease preventive medicine order predict development diseasepmid34003926 doi101093 rheumatology keab448,0.0
uncovering optic nerve sheath meningioma using 68gadotatate pet ct clin nucl med 2021 apr 5 doi 101097 rlu0000000000003619 online ahead printabstracta 56yearold woman initially diagnosed optic neuritis however several red flags present older age presentation multiple sclerosis suspicious findings mri negative oligoclonal bands 68gadotatate pet ct confirmed differential diagnosis optic sheath meningioma case stresses value somatostatin receptor ligand pet ct patients suspected optic neuritis diagnostic workup support immunemediated pathogenesispmid33826577 doi101097 rlu0000000000003619,0.0
second hit somatic pr905w novel germline intronmutation tsc2 gene found intestinal lymphangioleiomyomatosis case report literature review background tuberous sclerosis complex tsc autosomal dominant disorder characterized hamartomas multiple organs associated germline mutations tsc1 tsc2 including exonic intronic mosaic mutations gastrointestinal gi tract lymphangioleiomyomatosis lam extremely rare manifestation tsc reported cases herein aimed determine driver mutation pathogenesis relationship germline somatic mutations lam wholegenome sequencing wgs tumor blood samples whole transcriptome sequencing wts analysiscase presentationa nineyearold girl fullblown tsc presented abdominal masses detected routine checkup resected intestinal masses diagnosed lam thorough pathological examination interestingly lam presented somatic tsc2 gene mutation exon 24 pr905w cc2713t patient intron retention novel germline mutation intron region tsc2 chr162126489 c g conclusionour case suggests intron retention single nucleotide intronic mutation tsc2 sufficient develop severe manifestations tsc development lam requires additional somatic oncogenic mutation tsc2,0.0
cortical thickness serum nfl explain cognitive dysfunction newly diagnosed patients multiple sclerosis neurol neuroimmunol neuroinflamm 2021 aug 31 8 6 e1074 doi 101212 nxi0000000000001074 print 2021 novabstractbackground objectives determine relative importance global regional mri blood markers neurodegeneration neuroaxonal injury predicting cognitive performance recently diagnosed patients multiple sclerosis ms methods thirtyfive newly diagnosed patients relapsingremitting ms rrms 23 healthy controls hcs simultaneously completed full clinical neuropsychological assessment structural brain mri serum neurofilament light chain snfl level test linear regression analyses performed determine global regional measures gray matter gm atrophy cortical thickness ct combination snfl levels clinical scores strongly related neuropsychological impairmentresults compared hcs patients ms showed bilateral thalamic gm atrophy left p 0033 right p 0047 diminished ct particularly right superior transverse temporal gyri p 0045 p 0037 regional atrophy failed add predictive variance whereas anxiety symptoms snfl global ct best predictors r2 0404 p 0001 cognitive outcomes temporal thickness accounting greater variance cognitive deficits global ctdiscussion thalamic gm atrophy thinning temporal regions represent distinctive mri trait early stages ms although snfl levels alone clearly differentiate hcs patients rrms combination global regional ct snfl levels can better explain presence underlying cognitive deficits hence cortical thinning snfl increases can considered 2 parallel neurodegenerative markers pathogenesis progression newly diagnosed patients mspmid34465616 doi101212 nxi0000000000001074,0.0
assessing multiple sclerosisrelated quality life among iranian patients using msqol54 tool crosssectional study background multiple sclerosis ms chronic autoimmune disease one costly medical conditions imposed families catastrophic health expenditures increasing trend using alternative medicines including dietary supplements herbs vitamins minerals date association dietary well herbal supplements qol ms patients researched thus study aimed assess association selfreported supplement used qol ms patientsmethodsthis crosssectional study conducted patients ms referring shahid kazemi pharmacy based city tehran iran national pharmacy providing specialized pharmaceutical products pharmaceutical care patients multiple sclerosis quality life54 msqol54 tools performed evaluate ms patients qolresultsa total number 382 patients ms participated study include 89 233 men 293 767 women aged 40 109 years old overall score msqol54 questionnaire 4158 100 physical health composite phc mental health composite mhc 6960 6299 100 respectively study revealed 764 patients used least one vitamin daily 924 patients receive herbal product vitamin d widely used supplement followed calcium vitamin c least consumed correlation observed regarding supplement use overall qol phc mhc significant differences qols dimensions score patients used supplements results showed increasing number supplements used relate overall qol phc mhc addition correlation duration used supplements qols dimensions score ms patients pvalue 005 conclusionsthe dietary supplement appears popular among ms patients study results showed number supplementations longterm use patients ms associated higher qol similarly herbal supplements failed improve qol,0.0
association disease severity socioeconomic status black white americans multiple sclerosis neurology 2021 jun 30101212 wnl0000000000012362 doi 101212 wnl0000000000012362 online ahead printabstractobjective compare clinical imaging features multiple sclerosis ms severity black americans ba white americans wa evaluate role socioeconomic statusmethods compared ba wa participants multiple sclerosis partners advancing technology health solutions ms paths cohort respect ms characteristics including selfreported disability objective neurologic function assessments quantitative brain mri measurements covariate adjustment including education level employment insurance socioeconomic indicators subgroup evaluated withinrace neighborhoodlevel indicators socioeconomic status ses using 9digit zip codesresults 1 214 bas 7 530 ms bas younger lower education level likely medicaid insurance disabled unemployed bas worse selfreported disability 147fold greater odds severe vs mild disability 95 ci 118 186 worse performances tests cognitive processing speed 506 fewer correct ci 572 441 walking 066 seconds slower 95 ci 036 096 manual dexterity 211 seconds slower 95 ci 169 254 bas brain mri lesions lower overall gray matter brain volumes including reduced thalamic 077 ml 95 ci 091 064 cortical 3063 ml 95 ci 3593 2533 deep 158 ml 95 ci 192 123 gray matter volumes lower ses correlated worse neuroperformance scores association less clear baconclusion observed greater burden disease bas ms relative ms despite adjustment ses indicators beyond ses future longitudinal studies also consider roles societal constructs eg systemic racism studies will important identifying prognostic factors optimal treatment strategies among bas ms warrantedpmid34193590 doi101212 wnl0000000000012362,0.0
effects high low efficacy therapy secondary progressive multiple sclerosis neurology 2021 jun 30101212 wnl0000000000012354 doi 101212 wnl0000000000012354 online ahead printabstractobjective compare clinical effectiveness high lowefficacy treatments patients recently active inactive secondary progressive multiple sclerosis spms accounting therapeutic lagmethods patients treated high natalizumab alemtuzumab mitoxantrone ocrelizumab rituximab cladribine fingolimod lowefficacy interferon glatiramer acetate teriflunomide therapies spms onset selected msbase ofsep two large observational cohorts therapeutic lag estimated patient based demographic clinical characteristics propensity score used match patients treated high lowefficacy therapies outcomes disregarding period therapeutic lag compared paired pairwisecensored analysesresults 1000 patients included primary analysis patients active spms treated highefficacy therapy experienced less frequent relapses lowefficacy therapy hazard ratio hr 07 p0006 patients inactive spms evidence difference relapse frequency groups hr08 p039 evidence difference risk disability progression observedconclusion treated patients spms highefficacy therapy superior lowefficacy therapy reducing relapses patients active inactive spms however potent therapies offer advantage reducing disability progression patient groupclassification evidence study provides class iii evidence highefficacy therapy superior lowefficacy therapy reducing relapses patients active spms whilst find difference disability progression patients treated high lowefficacy therapypmid34193589 doi101212 wnl0000000000012354,0.0
altered synthesis genes associated shortchain fatty acids gut patients atrial fibrillation background gut microbiota provides health benefits humans producing shortchain fatty acids scfas whose deficiency causes multiple disorders inflammatory diseases however gut bacteria producing scfas patients atrial fibrillation af arrhythmia increasing prevalence reported investigate major gut microbial organisms related scfa synthesis scfasassociated kegg orthologues kos enzymatic genes potential producers examined according metagenomic datamining northern chinese cohort comprising 50 nonaf control 50 af patientsresultscompared nonaf controls individuals af marked differences microbial genes involved scfarelated synthesis including 125 kos 5 scfasrelated enzymatic genes furthermore 10 species harbored scfasynthesis related enzymatic genes markedly decreased gut af patients notably discriminative features scfasynthesis related function including 8 kos k01752 k01738 k00175 k03737 k01006 k01653 k01647 k15023 4 genes meni tesb ycia co dehydrogenase acetylcoa synthase complex 2 species coprococcus catus firmicutes bacterium cag103 selected key factors based lasso analysis furthermore plssem analysis showed 728 9114 overall effects gut microbiota diversity key species af respectively mediated key kos meanwhile 4631 total effects scfasynthesis related function left atrial enlargement mediated hscrp upon incorporation clinical properties af ko score still significantly associated af incidence 0004 p 0001 conclusionsthe current study revealed dysbiotic gut microbiota af coupled disrupted scfasynthesis related genes characterized decreased abundances kegg orthologues synthesis enzymatic genes harboring species,0.0
erratum predicting neuropsychological impairment relapsing remitting multiple sclerosis role clinical measures treatment neuropsychiatry symptoms arch clin neuropsychol 2021 jul 14acab063 doi 101093 arclin acab063 online ahead printno abstractpmid34259311 doi101093 arclin acab063,0.0
autologous haematopoietic stem cell transplantation active multiple sclerosis realworld case series neurology 2021 jul 12101212 wnl0000000000012449 doi 101212 wnl0000000000012449 online ahead printabstractobjective examine outcomes people multiple sclerosis pwms treated autologous hematopoietic stem cell transplantation ahsct realworld settingmethods retrospective cohort study pwms treated ahsct two centers london uk consecutively 2012 2019 6 months followup died time primary outcomes survival free ms relapses mri new lesions worsening expanded disability status scale edss adverse events rates also examinedresults cohort includes 120 pwms 52 progressive ms primary secondary 48 relapsingremitting ms rrms baseline median expanded disability status scale edss 60 90 evaluable cases showed mri activity 12 months preceding ahsct median followup ahsct 21 months range 685 ms relapsefree survival 93 2 years 87 4 years ahsct new mri lesions detected 90 subjects 2 years 85 4 years edss progressionfree survival pfs 75 2 years 65 4 years ebv reactivation monoclonal paraproteinemia associated worse pfs 3 transplantrelated deaths within 100 days 25 following fluid overload cardiac respiratory failureconclusions efficacy outcomes ahsct realworld cohort similar reported stringently selected clinical trial populations although risks may higherclassification evidence study rated class iv uncontrolled openlabel designpmid34253634 doi101212 wnl0000000000012449,0.0
investigation cerebral venous system multiple sclerosis summarybateman et al bateman et al 2021 shows multiple sclerosis ms strongly associated raised pressure superior sagittal sinus sss increased jugular bulb height sigmoid sinus findings consistent increased aqueductal csf pulse previously described ms reinforce hypothesis intracranial compliance reduced ms internal jugular vein abnormalities contribute sss hypertension however contribution pathophysiology ms established investigation therefore needed determine role changes play complex puzzle ms,0.0
purinergic signaling inflammasome activation psoriasis pathogenesis int j mol sci 2021 aug 31 22 17 9449 doi 103390 ijms22179449abstractpsoriasis chronic inflammatory disease skin associated systemic joint manifestations accompanied comorbidities metabolic syndrome increased risk cardiovascular disease psoriasis strong genetic basis exacerbation requires additional signals still largely unknown clinical manifestations involve interplay dendritic t cells dermis generate selfsustaining inflammatory loop around tnf il23 il17 axis forms psoriatic plaque addition recent years critical role keratinocytes establishing interplay leads psoriatic plaques formation reemerged review analyze recent evidence role keratinocytes danger associates molecular patterns extracellular atp generation psoriatic skin lesions particular attention will given purinergic signaling inflammasome activation initiation psoriasis phase keratinocytes inflammasome may trigger early inflammatory pathways involving il1 production elicit subsequent cascade events leads dendritic t cell activation since psoriasis likely triggered skindamaging events trauma can envisage intracellular atp released damaged cells may play role triggering inflammatory response underlying pathogenesis disease activating inflammasome therefore purinergic signaling skin represent new early step psoriasis thus opening possibility target single molecular actors purinome develop new psoriasis treatmentspmid34502368 doi103390 ijms22179449,0.0
taopatch combined homebased training protocol prevent sedentary lifestyle biochemical changes ms patients covid19 pandemic eur j transl myol 2021 aug 31 doi 104081 ejtm20219877 online ahead printabstractin multiple sclerosis ms important preserve residual physiological functions subjects aim present study investigate influence nanotechnological device treatment combined homebased training program tp lactate level hand grip strength cervical mobility ms patients seventeen ms patients enrolled study randomly assigned experimental group eg taopatch nanotechnological device applied control group cg participants carried cervical range motion 1 assessment hand grip test baseline t0 tp t1 also investigating lactate levels figure correlation possible changes investigated parameters results showed significant differences groups rom regards hand grip test eg showed statistically significant improvement strength hands dominant p 001 nondominant p 004 cg showed improvement nondominant hand p 0001 correlation found baseline lactate level cervical rom change can definitely conclude exercise taopatch can help improve maintain hand strength ms subjects also can prevent sedentary lifestyle covid19 pandemic time preliminary results need investigations possibly increasing sample size lengthening time interventionpmid34498450 doi104081 ejtm20219877,0.0
oligodendrocytespecific deletion fgfr1 reduces cerebellar inflammation neurodegeneration mog3555induced eae int j mol sci 2021 aug 31 22 17 9495 doi 103390 ijms22179495abstractmultiple sclerosis ms chronic inflammatory degenerative disease central nervous system cns ms commonly affects cerebellum causing acute chronic symptoms cerebellar signs significantly contribute clinical disability symptoms tremor ataxia dysarthria difficult treat fibroblast growth factors fgfs receptors fgfrs involved demyelinating pathologies ms autopsy tissue patients ms increased expression fgf1 fgf2 fgf9 fgfr1 found lesion areas recent research using mouse models focused regions spinal cord data expression fgf fgfr cerebellum available recent eae studies detected oligodendrocytespecific deletion fgfrs results milder disease course less cellular infiltrates reduced neurodegeneration spinal cord objective study characterize role fgfr1 oligodendrocytes cerebellum conditional deletion fgfr1 oligodendrocytes fgfr1ind achieved tamoxifen application eae induced using mog3555 peptide cerebellum analyzed histology immunohistochemistry western blot day 62 pi fgfr1ind mice showed less myelin axonal degeneration compared fgfr1competent mice infiltration cd3 + t cells mac3 + cells b220 + b cells igg + plasma cells cerebellar white matter lesions wml less fgfr1ind mice effects number opc mature oligodendrocytes white matter lesion wml expression fgf2 fgf9 associated less myelin axonal degeneration proinflammatory cytokines il1 il6 cd200 downregulated fgfr1ind mice fgf fgfr signaling protein pakt bdnf trkb increased fgfr1ind mice data suggest cellspecific deletion fgfr1 oligodendrocytes antiinflammatory neuroprotective effects cerebellum eae disease model mspmid34502405 doi103390 ijms22179495,1.0
neuromyelitis optica nmo iggdriven organelle reorganization human ipscderived astrocytes abstractneuromyelitis optica nmo autoimmune disease primarily targets astrocytes autoantibodies nmoigg water channel protein aquaporin 4 aqp4 serologic marker nmo patients known responsible pathophysiology disease brain aqp4 mainly expressed astrocytes especially endfeet form bloodbrain barrier following interaction nmoigg aqp4 astrocytes rapid aqp4 endocytosis initiates pathogenesis however cellular molecular mechanisms astrocyte destruction autoantibodies remain largely elusive established vitro human astrocyte model system using induced pluripotent stem cells ipscs technology combination nmo patientderived serum igg elucidate cellular functional changes caused nmoigg herein observed nmoigg induces structural alterations mitochondria association endoplasmic reticulum er lysosomes ultrastructural level potentially leads impaired mitochondrial functions dynamics indeed human astrocytes display impaired mitochondrial bioenergetics autophagy activity presence nmoigg demonstrated nmoiggdriven er membrane deformation multilamellar structure human astrocytes together show nmoigg rearranges cellular organelles alter functions vitro system using human ipscs offers previously unavailable experimental opportunities study pathophysiological mechanisms nmo human astrocytes conduct largescale screening potential therapeutic compounds targeting astrocytic abnormalities patients nmo,0.0
therapeutic aspects mesenchymal stem cellbased cell therapy focus human amniotic epithelial cells multiple sclerosis mechanistic review int j stem cells 2021 jun 30 doi 1015283 ijsc21032 online ahead printabstractmultiple sclerosis ms inflammatory disease central nervous system cns mmune system plays important role pathogenesis current treatments unable cure patients prevent progression ms lesions stem cellbased cell therapy opened new window ms treatment stem cells regulate immune responses improve axonal remyelination stem cells can obtained different origins embryonic neural bone marrow adipose tissues yet challenge selection best cell source stem cell therapy mesenchymal stem cells mscs type stem cell obtained different origins significant immunomodulatory effects immune system increasing evidence suggested umbilical cord adipose tissue can suitable source isolation mscs moreover human amniotic epithelial cells haecs novel stem cell origins immunoregulatory effects regenerative effects less capacity antigenicity can candidate ms treatment review discussed mechanistic effects mscs focus human amniotic epithelial cells can used treatment improvement outcome ms diseasepmid34158417 doi1015283 ijsc21032,1.0
congenital hepatic fibrosis mimics clinicopathologic study 19 cases single institution background congenital hepatic fibrosis chf rare inherited form ductal plate malformation associated polycystic kidney disease diagnosis requires histopathologic confirmation can challenging distinguish undefined fibrocystic liver diseases aimed describe clinicopathologic features congenital hepatic fibrosis chf comparisons entities may clinically histologically mimic chfmethodsnineteen cases carried clinical histologic impression chf identified institution histology reassessed reappraised two categories chf n13 mimics n6 clinicopathologic features two groups analyzed comparedresultsthe chf group subclassified clinical suspicion chfc n8 incidental histology findings chfi n5 patients chfi much older chfc mimics p005 male female equally affected six 8 chfc 667 concurrent kidney diseases including 5 polycystic kidney diseases five 6 mimics 833 various kidney diseases including nephronophthisis alport syndrome renal agenesis nephrolithiasis none chfi patients kidney disease 3 associated hepatic carcinomas histology analysis demonstrated characteristic triads bile duct abnormalities portal vein hypoplasia fibrosis chf cases one mimic paucity intrahepatic bile ducts 5 mimics showed abnormal portal veins nodular regenerative hyperplasia consistent hepatoportal sclerosis hps conclusionsour study demonstrates classic histology triad chf despite wide spectrum clinical presentations hps unexpectedly clinical mimicker chf can distinguished histologically,0.0
validated generally applicable approach using systematic assessment disease modules gwas reveals multiomic module strongly associated risk factors multiple sclerosis background exist practical guidelines predictive falsifiable multiomic data integration systematically integrate existing knowledge disease modules popular concepts interpreting genomewide studies medicine far systematically evaluated may lead corroborating multiomic modulesresultwe assessed eight module identification methods 57 previously published expression methylation studies 19 diseases using gwas enrichment analysis next applied strategy multiomic integration 20 datasets multiple sclerosis ms validated resulting module using gwas riskfactorassociated genes several independent cohorts benchmark modules showed immuneassociated diseases modules inferred cliquebased methods enriched gwas genes multiomic case study using ms data revealed robust identification module 220 genes strikingly genes module differentially methylated upon action one several environmental risk factors ms n 217 p 10 47 also independently validated association five different risk factors ms stressed high genetic epigenetic relevance module msconclusionswe believe analysis provides workflow selecting modules benchmark study may help improvement disease module methods moreover also stress methodology generally applicable combining assessing performance multiomic approaches complex diseases,0.0
managing anxiety among multiple sclerosis patients covid19 pandemic j res med sci 2021 aug 30 2668 doi 104103 jrmsjrms_633_20 ecollection 2021no abstractpmid34729076 pmcpmc8506257 doi104103 jrmsjrms_633_20,0.0
tfh cells systemic sclerosis abstractsystemic sclerosis autoimmune disease characterized excessive dermal fibrosis progression internal organs vascular impairment immune dysregulation evidenced infiltration inflammatory cells affected tissues production auto antibodies pathogenesis remains unclear several data highlight t b cells deregulation implicated disease pathogenesis last decade aberrant responses circulating t follicular helper cells subset cd4 t cells able localise predominantly b cell follicles high level chemokine receptor cxcr5 expression described pathogenesis several autoimmune diseases chronic graftversushostdisease present review summarized observed alteration number frequency circulating t follicular helper cells systemic sclerosis described role aberrant b cell activation differentiation though interleukine21 secretion also clarified t follicular helperlike cells involvement fibrogenesis human mouse model finally t follicular helper cells involved fibrosis autoimmune abnormalities systemic sclerosis patients presented different strategies used target t follicular helper cells systemic sclerosis therapeutic trials currently carried future perspectives autoimmune diseases graftversushostdisease models,0.0
proposed mobility assessments simultaneous fullbody inertial measurement units optical motion capture healthy adults neurological patients future validation studies study protocol sensors basel 2021 aug 30 21 17 5833 doi 103390 s21175833abstracthealthy adults neurological patients show unique mobility patterns course lifespan disease quantifying mobility patterns support diagnosing tracking disease progression measuring response treatment quantification can done wearable technology inertial measurement units imus imus can used quantify mobility algorithms need developed validated age diseasespecific datasets study proposes protocol dataset can used develop validate imubased mobility algorithms healthy adults 1860 years healthy older adults 60 years patients parkinsons disease multiple sclerosis symptomatic stroke chronic low back pain participants will measured simultaneously imus 3d optical motion capture system performing standardized mobility tasks nonstandardized activities daily living specific clinical scales questionnaires will collected study aims building largest dataset development validation imubased mobility algorithms healthy adults neurological patients anticipated provide dataset research use collaboration ultimate goal bring imubased mobility algorithms quickly possible clinical trials clinical routinepmid34502726 doi103390 s21175833,0.0
dietary risk factors primary progressive multiple sclerosis populationbased casecontrol study abstractobjectivesthere growing evidences role nutritional factors multiple sclerosis ms occurrence dietary data limited primary progressive type ms ppms assessed role dietary factors adolescence ppms riskmethodsan incident casecontrol study 143 ppms cases definite diagnosis 400 controls conducted sina hospital tehran iran demographic data collected data nutritional habits adolescence obtained using questionnaire designed multinational casecontrol studies environmental risk factors multiple sclerosis envimsq logistic regression models run evaluate role diet ppms riskresultsa significant association founded higher intake dairy seafood red meat poultry vegetable fruit nut lower risk ppms p 005 association dose dependent mentioned food groups except fruit fully adjusted model intake dairy 027 95ci 014053 seafood 021 95ci 010044 red meat or044 95ci 022090 vegetable 019 95ci 009039 fruit 047 95ci 022099 nut 029 95ci 015056 third tertiles resulted significant reduction ppms risk case poultry consumption association meaningful just third tertile crude model 054 95ci 030095 nutrient supplementation calcium iron folic acid vitamin b12 c also related 84 lower risk ppmsconclusionour data proposed adequate intake food groups nutrient supplementation adolescence may effective reducing adultonset ppms risk,0.0
patients neuromyelitis optica spectrum disorder nmosd associated adverse outcome total hip arthroplasty matched casecontrol study background neuromyelitis optica spectrum disorders nmosd rare inflammatory diseases central nervous system cause transverse myelitis optic neuritis steroids commonly administered nmosd patients use steroids may lead osteonecrosis makes nmosd patients candidate total hip arthroplasty tha date clinical outcome tha nmosd patients investigatedaiminvestigate patient reported outcome measures prom radiographic outcome complication nmosd patients tha compared nonnmosd patientsmethodspatients jan 2016 october 2020 identified database 12 nmosd cases met inclusion criteria matched nonnmosd cases ratio 12 based age sex charlson comorbidity index cci surgical date relevant outcome analyzed compared two groupsresultsthere significantly increased risk dislocation nmosd patients postoperative hoos score similar two groups even though preoperative hoos score significantly higher nonnmosd group nmosd patients poor performance eq5d eqvas cups placed anteverted nmosd cases p 001 conclusionthere significantly increased risk dislocation tha nmosd patients however satisfactory improvement functional outcome hip achieved due natural process nmosd rehabilitation hip precaution patientspecific timespecific,0.0
clinical predictors disease progression cohort progressive tunisian multiple sclerosis abstractbackgroundknowledge progressive multiple sclerosis ms mainly based caucasian studies northafrican context ms exhibits particular characteristics mainly related severe phenotype given limited data available imminent need characterize progressive ms latitudesobjectiveto describe specificities progressive ms identify inherent clinical predictors disability accrual tunisian cohortmethodsa retrospective hospitalbased study conducted department neurology razi hospital patients diagnosed ms divided relapsing ms rrms secondary progressive ms spms primary progressive ms ppms epidemiological clinical paraclinical data compared among three groupsresultsof 504 patients progressive ms described among 115 patients percentage 228 divided 139 spms 89 ppms first clinical attack motor symptoms revealed predominant ppms 911 spms onset median time 10 years significantly delayed patients visual onset full recovery first relapse patients progressive ms exhibited rapid disability accumulationconclusioncompared caucasians tunisians exhibited faster rate conversion spms according natural progressive ms history early clinical features predictors ms disability accrual,0.0
level stress coping strategies patients multiple sclerosis relationships disease course j clin med 2021 aug 30 10 17 3916 doi 103390 jcm10173916abstractobjectives stress supposed linked background multiple sclerosis ms disease coursedesign study aimed assess level stress coping strategies ms patients within year followup investigate relationships aspects factors relatedor notto msmethods 65 patients ms perceived stress scale pss10 type d scale ds14 coping orientations problems experienced cope performed baseline year baseline pss10 ds14 cope scores analyzed regard demographics ms duration treatment indices disability selfreported stressful events ses final pss10 cope results analyzed reference ms activity se within year followupresults initially 67 patients reported moderate high level stress 31 met typed personality criteria diverse coping strategies preferred problemfocused negative affectivity ds14 subscore neg correlated disability level nonhealthrelated ses associated higher pss10 neg scores year mean pss10 score decreased cope results change significantly nonhealthrelated ses associated higher pss10 score less frequent use acceptance humor strategies active vs stable ms course followup differ terms pss10 cope resultsconclusions ms patients experienced increased level stress significant relationships found stress coping ms course within year nonhealthrelated factors affected measures stress msrelated factorspmid34501362 doi103390 jcm10173916,0.0
astrocytic potassium calcium channels integrators inflammatory ischemic cns microenvironment biol chem 2021 aug 30 doi 101515 hsz20210256 online ahead printabstractastrocytes key regulators surroundings receiving integrating stimuli local microenvironment thereby regulating glial neuronal homeostasis cumulating evidence supports plethora heterogenic astrocyte subpopulations differ morphologically expression patterns receptors transporters ion channels well functional specialisation astrocytic heterogeneity especially relevant pathological conditions experimental autoimmune encephalomyelitis eae mouse model multiple sclerosis ms morphologically distinct astrocytic subtypes identified linked transcriptome changes different disease stages regions allow continuous awareness changing stimuli across age diseases astrocytes equipped variety receptors ion channels allowing precise perception environmental cues recent studies implicate diverse repertoire astrocytic ion channels including transient receptor potential channels voltagegated calcium channels inwardly rectifying k+ channels twopore domain potassium channels sensing brain state physiology inflammation ischemia review current evidence regarding astrocytic potassium calcium channels functional contribution homeostasis neuroinflammation strokepmid34455729 doi101515 hsz20210256,0.0
radiological mid longterm patientreported outcome stabilization traumatic thoracolumbar spinal fractures using expandable vertebral body replacement implant background treatment unstable thoracolumbar burst fractures combined posterior anterior stabilization instead posterioronly instrumentation recommend current literature due instability anterior column data restoring bisegmental kyphotic endplate angle bka expandable vertebral body replacements vbr mid longterm patientreported outcome measures prom sparsemethodsa retrospective cohort study patients traumatic thoracolumbar spinal fractures treated expandable vbr implant obelisc ulrich medical germany 2001 2015 conducted patient treatment characteristics evaluated retrospectively radiological data acquisition completed pre postoperatively 6 months least 2 years vbr surgery bka measured fusionrates assessed sf36 eq5d odi questionnaires evaluated prospectivelyresultsninetysix patients 25 female 71 male age 461 128 years included study ao type a4 fracture seen 80 96 cases 833 seventythree fractures 760 located lumbar spine intraoperative reduction bka n 96 patients 105 94 p 001 loss correction 10 28 first followup t1 24 40 second followup t2 measured p 005 bony fusion rate 979 total revision rate 42 fiftyone patients 531 included patients age 489 124 years completed prom questionnaires 1064 443 months therefore assigned respondent group mean odi score 282 183 mean eq5d vas reached 607 41 points stratified sf36 results iss 16 lower compared reference populationconclusionthe treatment traumatic thoracolumbar fractures expandable vbr implant lead high rate bony fusion significant correction bka achieved clinically relevant loss reduction occurred followup even though health related quality life reach normative population values overall satisfactory results reported,0.0
tramadol induced jerks cureus 2021 aug 29 13 8 e17547 doi 107759 cureus17547 ecollection 2021 augabstractmyoclonus sudden involuntary jerking muscle group muscles myoclonus may present form pattern sporadically infrequently usually associated neurological disorders epilepsy multiple sclerosis infections tumors central nervous system myoclonus commonly known caused tramadol present case 59yearold male developed myoclonus muscles trunk 10 days initiating tramadol chronic pain myoclonus disappeared withholding medication purpose case report make clinicians aware rare reversible side effect use tramadolpmid34646604 pmcpmc8481130 doi107759 cureus17547,0.0
investigating microstructural changes white matter multiple sclerosis systematic review metaanalysis neurite orientation dispersion density imaging brain sci 2021 aug 29 11 9 1151 doi 103390 brainsci11091151abstractmultiple sclerosis ms characterised widespread damage central nervous system includes alterations normalappearing white matter nawm demyelinating white matter wm lesions neurite orientation dispersion density imaging noddi proposed provide precise characterisation wm microstructures noddi maps can calculated neurite density index ndi orientation dispersion index odi estimate orientation dispersion neurite density although noddi widely applied ms technique promising investigating complexity ms pathology specific diffusion tensor imaging dti capturing microstructural alterations conducted metaanalysis studies using noddi metrics assess brain microstructural changes neuroaxonal pathology wm lesions nawm patients ms three reviewers conducted literature search four electronic databases performed randomeffect metaanalysis extent betweenstudy heterogeneity assessed i2 statistic funnel plots eggers tests used assess publication bias identified seven studies analysing 374 participants 202 ms 172 controls ndi wm lesions nawm significantly reduced compared healthy wm standardised mean difference 308 95ci 422 195 p 000001 i2 88 070 95ci 099 040 p 000001 i2 35 respectively statistically significant difference odi ms wm lesions nawm compared healthy controls systematic review metaanalysis confirmed ndi significantly reduced ms lesions nawm wm healthy participants corresponding reduced intracellular signal fraction may reflect underlying damage loss neuritespmid34573172 doi103390 brainsci11091151,1.0
preliminary investigation effects obstacle negotiation turning gait variability adults multiple sclerosis sensors basel 2021 aug 28 21 17 5806 doi 103390 s21175806abstractmany falls persons multiple sclerosis pwms occur daily activities negotiating obstacles changing direction increased gait variability robust biomarker fall risk pwms gait variability ecologically related tasks unclear effects turning negotiating obstacle gait variability pwms investigated pwms matched healthy controls instrumented inertial measurement units feet lumbar torso subjects completed walk turn wt without obstacle crossing ow task partitioned preturn postturn preobstacle postobstacle phases analysis spatial temporal gait measures measures trunk rotation captured phase task wt condition pwms demonstrated significantly variability lumbar trunk yaw range motion rate lateral foot deviation cadence step time turning ow condition pwms demonstrated significantly variability spatial temporal gait parameters obstacle approach turning compared turning significant differences gait variability observed negotiating obstacle regardless turning results suggest context gait variability measurement important increased number variables impacted turning influence turning obstacle negotiation suggest varying tasks must considered together rather isolation obtain informed understanding gait variability closely resembles everyday walkingpmid34502697 doi103390 s21175806,0.0
associations clinical characteristics dual task performance multiple sclerosis depend cognitive motor dual tasks used abstractbackground persons multiple sclerosis pwms performing simultaneous cognitive task walking often results slower gait clinical characteristics associated reduced dual task dt performance yet entirely clear multicentre study aimed determine relationship clinical demographical characteristics dual task dt walking performance pwms multiple dt conditionsmethods nine dt conditions analysed consisting combinations three types cognitive digit spannull subtractionnull vigilancenull three types walking walknull walk cupnull walk obstaclesnull conditions primary outcomes dt gait speed m s motor dt cost gait speed dtcmotor secondary outcomes clinical tests physical cognitive functioning patientreported demographical outcomes firstly univariate analyses subsequently multivariate analyses backward modelling conducted type walking dt condition separately cognitive dt conditions included models main interaction effect secondary outcomesresults analysis performed 81 pwms edss 3310 final models dtcmotor significant main effects walknull dtconditions symbol digit modalities test sdmt cupnull conditions sdmt dynamic gait index obstaclesnull conditions age dt gait speed main effects found 2minute walking test 2mwt multiple sclerosis walking scale walking conditions additionally interactions cognitive dtconditions sdmt age 2mwt foundconclusion clinical characteristics related dt walking performance differed according cognitivemotor dtcondition used still general pwms better mobility demonstrated higher dt gait speed faster information processing speed related lower dtcmotor,0.0
risk dementia patients toxoplasmosis nationwide populationbased cohort study taiwan background approximately 2530 individuals worldwide infected toxoplasma gondii t gondii difficult detect latent state aimed evaluate association toxoplasmosis risk dementia effects antibiotics taiwanmethodsthis nationwide populationbased retrospective cohort study conducted using longitudinal health insurance database containing records 2 million individuals retrieved taiwans national health insurance research database finegray competing risk analysis used determine risk development dementia toxoplasmosis cohort relative nontoxoplasmosis cohort sensitivity analysis also conducted effects antibiotics sulfadiazine clindamycin risk dementia also analyzedresultswe enrolled total 800 subjects identified 200 patients toxoplasmosis 600 sex agematched controls without toxoplasmosis infection ratio 13 selected 2000 2015 crude hazard ratio hr risk developing dementia 2570 95 confidence interval ci 15114347 p 0001 adjusting sex age monthly insurance premiums urbanization level geographical region comorbidities adjusted hr 2878 95 ci 17094968 p 0001 sensitivity analysis revealed toxoplasmosis associated risk dementia even excluding diagnosis first year first 5 years usage sulfadiazine clindamycin treatment toxoplasmosis associated decreased risk dementiaconclusionsthis finding supports evidence toxoplasmosis associated dementia antibiotic treatment toxoplasmosis associated reduced risk dementia studies necessary explore underlying mechanisms associationsgraphical abstract,0.0
epiphaknee trial explaining pain target unhelpful pain beliefs increase physical activity knee osteoarthritis protocol multicentre randomised controlled trial clinical costeffectiveness analysis background despite wellestablished benefits physical activity knee osteoarthritis oa nine ten people knee oa inactive people knee oa inactive often believe physical activity dangerous fearing will damage joint s unhelpful beliefs can negatively influence physical activity levels aim evaluate clinical costeffectiveness integrating physiotherapistdelivered pain science education pse evidencebased conceptual change intervention targeting unhelpful pain beliefs increasing pain knowledge individualised walking strengthening general education programmethodstwoarm paralleldesign multicentre randomised controlled trial involving 198 people aged 50 years painful knee oa meet physical activity guideline recommendations walk regularly exercise groups receive individualised physiotherapistled walking strengthening oa activity education program via 4x weekly inperson treatment sessions followed 4 weeks athome activities weekly checkin via telehealth followup sessions 3 months telehealth 5 9 months inperson epiphaknee group also receives contemporary pse oa pain activity embedded aspects intervention outcomes assessed baseline 12 weeks 6 12 months primary outcomes physical activity level step count wristbased accelerometry selfreported knee symptoms womac total score 12 months secondary outcomes quality life pain intensity global rating change selfefficacy pain catastrophising depression anxiety stress fear movement knee awareness oa activity conceptualisation selfregulated learning ability additional measures include adherence adverse events blinding success covid19 impact activity intention exercise treatment expectancy perceived credibility implicit movement environmental bias implicit motor imagery twopoint discrimination pain sensitivity activity costutility analysis epiphaknee intervention will undertaken addition evaluation costeffectiveness context primary trial outcomesdiscussionwe will determine whether integration pse individualised oa education walking strengthening program effective receiving individualised program alone findings will inform development implementation future delivery pse part best practice people knee oatrial registrationaustralian new zealand clinical trials registry actrn12620001041943 13 10 2020,0.0
dimethyl fumarate inhibits antibodyinduced platelet destruction immune thrombocytopenia mouse background immune thrombocytopenia itp autoimmune disease characterized low platelet count resulting immunemediated platelet destruction dimethyl fumarate dmf widely applied treatment several autoimmune diseases immunosuppressive effect however whether ameliorates itp unclear study aims evaluate whether dmf preventive effect itp micemethodsdmf 30 60 90 mg kg body weight intraperitoneally injected mice followed injection rat antimouse integrin gpiib cd41antibody induce itp peripheral blood isolated measure platelet count spleen mononuclear cells extracted measure th1 treg cells along detecting levels ifn tgf1 plasma cd68 expression spleen immuohistochemical staining additionally macrophage cell line raw2647 cultured treated dmf followed analysis cell apoptosis cycle expression fcri fcriib fcriv mrnaresultsdmf significantly inhibited antiplatelet antibodyinduced platelet destruction decreased th1 cells expression tbet ifn upregulated treg cells expression foxp3 tgf1 well reduced cd68 expression spleen itp mouse dmftreated raw2647 cells showed sphase arrest increased apoptosis downregulated expression fcri fcriv meanwhile vitro treatment dmf also decreased expression cyclin d1 e2 reduced bcl2 level increased bax expression caspase3 activationconclusionsin conclusion dmf prevents antibodymediated platelet destruction itp mice possibly promoting apoptosis indicating might used new approach treatment itp,0.0
recurrent lymphangioleiomyomatosis lung allograft covid19 autopsy case report literature review abstractlymphangioleiomyomatosis lam rare neoplastic disease lung characteristic feature diffuse cystic changes bilateral lungs lung transplantation considered one effective treatments end stage disease patients lam underwent lung transplant tend favorable outcome compared end stage lung diseases report case female patient diagnosed lam received bilateral lung transplantation 45 years age subsequent allograft biopsies significant mild acute cellular rejection grade a2 immunosuppressive regimen adjusted accordingly 7 years posttransplant presented shortness breath cough fatigue diagnosed viral infection chest imaging unremarkable however transbronchial biopsy performed rule rejection revealed foci spindle cells proliferation positive hmb45 smooth muscle actin immunohistochemical studies confirming diagnosis recurrent lam discharged readmitted 1 week later severe covid19 clinical course complicated acute respiratory distress syndrome respiratory failure gastrointestinal hemorrhage patient passed away day 36 hospital stay autopsy requested confirmed pathology recurrent lam diffuse alveolar damage covid19,0.0
phase 3 doubleblind placebocontrolled efficacy safety study ads5102 amantadine extendedrelease capsules people multiple sclerosis walking impairment abstractbackgroundads5102 delayedrelease extendedrelease dr er amantadine improved walking speed ms phase 2 trialobjectivethe aim study present primary results phase 3 doubleblind ads5102 trial inroads walking speedmethodsadult participants ms walking impairment currently using amantadine dalfampridine underwent 4week placebo runin randomization 111 placebo 137 274mg day ads5102 12weeks primary outcome proportion responders 20 increase timed 25foot walk t25fw speed 274mg ads5102 versus placebo end doubleblind study week 16 additional measures included timed go tug 2minute walk test 2mwt 12item multiple sclerosis walking scale msws12 resultsin total 558 participants randomized received doubleblind treatment significantly participants responded 274mg ads5102 211 versus placebo 113 mean t25fw speed also significantly improved 019ft s versus placebo 007ft s measures significant using prespecified hierarchical testing procedure adverse events led discontinuation 38 placebo 64 137mg ads5102 205 274mg ads5102 conclusioninroads met primary endpoint showing significantly greater proportion participants meaningful improvement walking speed 274mg ads5102 versus placebo numeric dose response seen secondary efficacy outcomes adverse events,0.0
overview peptidebased molecules potential drug candidates multiple sclerosis molecules 2021 aug 28 26 17 5227 doi 103390 molecules26175227abstractmultiple sclerosis ms belongs demyelinating diseases progressive highly debilitating pathologies imply high burden individual patients society currently several treatment strategies differ route administration adverse events possible risks side effects associated multiple sclerosis medications range mild symptoms flulike irritation injection site serious ones progressive multifocal leukoencephalopathy lifethreatening events moreover agents far available proved incapable fully preventing disease progression mostly phases consist continuous accumulating disability thus new treatment strategies able halt even reverse disease progression specific targeting solely pathways contribute disease pathogenesis highly desirable provide overview recent literature peptidebased systems tested experimental autoimmune encephalitis eae models since peptides considered unique therapeutic niche important elements pharmaceutical landscape open new therapeutic opportunities treatment mspmid34500662 doi103390 molecules26175227,1.0
time diagnosis multiple sclerosis epidemiological data german multiple sclerosis registry abstractobjectiveto investigate time diagnosis multiple sclerosis ms germanymethodsanalysis realworld registry data german multiple sclerosis registry gmsr performing primary analysis patients monthspecific registration dates onset diagnosis availableresultsas january 2020 data total 28 658 patients ms extracted gmsr 9836 patients included primary analysis mean time diagnosis shorter following introduction first magnetic resonance imaging mri based mcdonald criteria 2001 effect pronounced younger adults age 40 years relapsing onset multiple sclerosis roms decrease 19 years 2010 09 years 2020 unchanged patients aged 4050 years 14 years 2010 13 years 2020 limited number paediatric onset ms patients time diagnosis longer change 29 years conclusionthe current sensitive mribased diagnostic criteria likely contributed earlier diagnosis ms germany younger adults aged 1839 years roms whether translated earlier initiation diseasemodifying treatment beneficial effect patient outcomes remains demonstrated,0.0
cerebrospinal tau levels predictor early disability multiple sclerosis abstractintroduction axonal loss important feature multiple sclerosis ms strongly related irreversible disability accumulation nonetheless exact mechanisms underlying axonal loss remain unclear cerebrospinal fluid csf levels tau betaamyloid abeta currently represent diagnostic biomarkers neurodegenerative diseases ms studies csf tau abeta provided preliminary informations disease prognosis results yet replicatedmethods investigated whether csf tau abeta levels predict early disability accumulation ms patients 100 patients underwent csf analysis diagnostic workup demographic clinical radiological features csf collected baseline ms severity score msss agerelated msss armss calculated last followup performed mannwhitney test spearmannulls coefficient multiple regression analysis significant predictors disability based csf abeta tau levels gender age diagnosis mri characteristics baselineresults baseline csf tau levels moderately correlated msss r0372 p00001 weakly armss r0237 p00176 mean two years followup predictors early disability evaluated msss armss csf tau beta0258 p0009 beta0252 p001 spinal cord involvement beta0196 p0029 beta0240 p0008 well age ms diagnosis beta0286 p0001 msss high brain lesion load beta0207 p002 armssconclusion csf tau levels diagnosis possibly predictive value along mri features age diagnosis hypothesize tau levels may express chronic axonal damage possibly contributing early ms disability,0.0
apolipoprotein e receptor 2 deficiency decreases endothelial adhesion monocytes protects autoimmune encephalomyelitis sci immunol 2021 aug 27 6 62 eabd0931 doi 101126 sciimmunolabd0931abstractunder normal conditions bloodbrain barrier effectively regulates passage immune cells central nervous system cns however pathological conditions multiple sclerosis ms leukocytes especially monocytes infiltrate cns promote inflammatory demyelination resulting paralysis therapies targeting immune cells directly preventing leukocyte infiltration exist ms may compromise immune system explore apolipoprotein e receptor 2 apoer2 regulates vascular adhesion infiltration monocytes inflammation induced experimental autoimmune encephalitis apoer2 knockout mice mice carrying lossoffunction mutation apoer2 cytoplasmic domain models paralysis neuroinflammation largely abolished result greatly diminished monocyte adherence due reduced expression adhesion molecules endothelial surface findings expand mechanistic understanding vascular barrier regulation inflammation vascular permeability therapeutic potential apoer2targeted therapiespmid34452924 doi101126 sciimmunolabd0931,1.0
comparative efficacy safety anticd20 monoclonal antibodies relapsingremitting multiple sclerosis network metaanalysis ibro neurosci rep 2021 aug 27 11103111 doi 101016 jibneur202108003 ecollection 2021 decabstractwith recent successful targeting b lymphocytes patients multiple sclerosis ms treatment anticd20 monoclonal antibodies mabs may represent promising managemental approach particularly relapsing remitting ms rrms network metaanalysis conducted based comprehensive search embase pubmed cochrane library assess comparative efficacy safety currently available anticd20 monoclonal antibodies mabs including rituximab ocrelizumab ofatumumab versus common comparator interferon beta1a inf1a rrms patients recruited randomized clinical trials rcts frequentist network metaanalytical model annualized relapse rates arrs safety outcomes expressed risk ratios rrs whereas relapsefree events expressed odds ratios ors treatment ranking performed using pscores certainty evidence appraised using grade approach five publications reported outcomes seven rcts 3938 patients 6709 females compared inf1a ocrelizumab reduced risk arr rr 056 95 ci 050064 serious adverse events rr 017 95 ci 009030 treatment discontinuation due adverse events saes rr 060 95 ci 039093 associated higher odds relapses 247 95 ci 200305 ocrelizumab ranked best among treatments terms reducing arr saes quality evidence low ocrelizumab low moderate rituximab high ofatumumab largesized welldesigned rcts needed corroborate efficacy safety ocrelizumab anticd20 mabs rrmspmid34505112 pmcpmc8411244 doi101016 jibneur202108003,0.0
multidisciplinary approach prenatal diagnosis tsc cardiac rhabdomyoma initial symptom front pediatr 2021 aug 27 9628238 doi 103389 fped2021628238 ecollection 2021abstractthe longterm prognosis fetus cardiac rhabdomyoma cr depends correlation tuberous sclerosis complex tsc recent years numerous variations uncertain significance vus tsc genes produced highthroughput sequencing made counseling challenging studies now tended sidestep tricky topics integrated detailed parental phenotype echocardiography neuro mri genetic information conduct comprehensive evaluation 61 cr fetuses result multiple crs cerebral lesions appeared 90 80 respectively fetuses pathogenic p likely pathogenic lp tsc1 tsc2 variations overall 857 liveborn infants p lp presented tscassociated signs 857 vus without nervous findings good prognoses genetic evidence cerebral mri findings sensitive index assess longterm prognosis complement confirm tsc diagnosis total 689 fetuses cr benefit multidisciplinary approach turned potentially clinically actionable precise clinical genetic diagnosis foreseeable outcome practice provides practical feasible solution perinatal management prognostic guidance fetuses crpmid34513752 pmcpmc8429840 doi103389 fped2021628238,0.0
tfeb phosphorylation serine 211 induced autophagy human synovial fibroblasts p62 sqstm1 overexpression hek293 cells biochem j 2021 aug 18bcj20210174 doi 101042 bcj20210174 online ahead printabstractautophagy receptor p62 sqstm1 signals complex network links autophagylysosomal system proteasome phosphorylation p62 serine 349 pser349 p62 involved cell protective antioxidant pathway shown previously pser349 p62 occurs rapidly degraded human synovial fibroblasts autophagy work observed fingolimod fty720 used medication multiple sclerosis induced coordinated expression p62 pser349 p62 inhibitory tfeb form phosphorylated serine 211 pser211 tfeb human synovial fibroblasts effects mimicked potentiated proteasome inhibitor mg132 addition fty720 induced autophagic flux lc3bii upregulation akt phosphorylation inhibition serine 473 downregulated tfeb suggesting stalled autophagy fty720 decreased cytoplasmic fraction contained tfeb induced tfeb nuclear fraction fty720induced pser211 tfeb mainly found membrane fraction autophagy vps34 kinase inhibitor autophinib increased fty720induced pser349 p62 inhibited concomitant expression pser211 tfeb results suggested pser211 tfeb expression depends autophagy overexpression gfp tagged tfeb hek293 cells showed concomitant expression phosphorylated form serine 211 downregulated autophinib results suggested autophagy might autoregulated pser211 tfeb negative feedback loop interest overexpression p62 p62 phosphorylation mimetic s349e mutant phosphorylation deficient mutant s349a hek293 cells markedly induced pser211 tfeb results showed p62 involved regulation tfeb phosphorylation serine 211 involvement depend p62 phosphorylation serine 349pmid34405859 doi101042 bcj20210174,0.0
complications covid19 pneumonia multiple sclerosis exacerbation cureus 2021 aug 27 13 8 e17506 doi 107759 cureus17506 ecollection 2021 augabstractmultiple sclerosis ms common autoimmune disease united states demyelination brain spinal cord disrupts transmission signals throughout body average life expectancy 30 years start disease treatment relies symptom management steroids diseasemodifying agents cure ms patients shown increased risk coronavirus disease 19 covid19 infection prolonged hospitalizations severe covid19 sequelae linked various ms subgroups limited studies however reported role covid19 precipitating ms exacerbations flareups often occur times stress immunological insult present 45yearold patient relapsingremitting multiple sclerosis whose neurological symptoms worsened sharply weeks following inpatient admission covid19 pneumoniapmid34603883 pmcpmc8476193 doi107759 cureus17506,1.0
dna methyltransferase inhibitors combination therapy treatment solid tumor mechanism clinical application abstractdna methylation epigenetic modification regulates gene transcription maintains genome stability dna methyltransferase dnmt inhibitors can activate silenced genes low doses cause cytotoxicity high doses ability dnmt inhibitors reverse epimutations basis use novel strategies cancer therapy review examined literature dna methyltransferase inhibitors summarized mechanisms underlying combination therapy using dnmt inhibitors clinical trials based combining hypomethylation agents chemotherapeutic drugs also discussed efficacy compounds antitumor agents need optimize treatment schedules regimens maximal biologic effectiveness notably combination dnmt inhibitors chemotherapy immune checkpoint inhibitors may provide helpful insights development efficient therapeutic approaches,0.0
sarscov2 infection central nervous system 14monthold child case report complete autopsy background neurological systemic complications occur adults severe covid19 describe sarscov2 infection complicated neuroinvasion postmortem tissues child methods performed complete autopsy 14monthold child died covid19 pneumonitis histological sections multiple organs stained haematoxylin eosin luxol fast blue staining myelin immunohistochemistry performed selected areas brain presence sarscov2 investigated immunostaining antispike protein antibody rtqpcr findings lesions included microthrombosis pulmonary congestion interstitial oedema lymphocytic infiltrates bronchiolar injury collapsed alveolar spaces cortical atrophy severe neuronal loss sarscov2 staining observed along apical region choroid plexus chp epithelium ependymal cells lateral ventricle restricted chp capillaries vessels regions sarscov2 infection brain tissue confirmed rtqpcr fragments chp lateral ventricle cortex interpretation results show multisystemic histopathological alterations caused sarscov2 infection contribute knowledge regarding course fatal covid19 children furthermore findings chp infection viral neurotropism suggest sarscov2 may invade central nervous system bloodcerebrospinal fluid barrier disruption funding carlos chagas filho foundation supporting research state rio de janeiro faperj national council scientific technological development cnpq coordination improvement higher education personnel capes addition intramural grants dor institute research education,1.0
brie2 computational identification splicing phenotypes singlecell transcriptomic experiments abstractrna splicing important driver heterogeneity single cells expression alternative transcripts determinant transcriptional kinetics however intrinsic coverage limitations scrnaseq technologies make challenging associate specific splicing events celllevel phenotypes brie2 scalable computational method resolves issues regressing singlecell transcriptomic data celllevel features show brie2 effectively identifies differential diseaseassociated alternative splicing events allows principled selection genes capture heterogeneity transcriptional kinetics improve rna velocity analyses enabling identification splicing phenotypes associated biological changes,0.0
role oxidative stress haematological parameters relapsingremitting multiple sclerosis kurdish population abstractbackgroundmultiple sclerosis ms neurodegenerative disorder exhibits inflammation oxidative stress hallmarksobjectivethe research aims know disturbances haematological parameters antioxidant system relapsingremitting multiple sclerosis rrms patients kurdish populationmethodsa casecontrol research meeting following mcdonald criterion conducted 100 rrms patients 100 controlsresultslipid peroxidation products malondialdehyde mda erythrocyte sedimentation rate esr total leukocyte counts tlcs increased significantly copper cu+2 superoxide dismutase sod decreased significantly nitric oxide metabolites nox lymphocyte changed significantly compared controlsconclusionfindings study revealed defects detected haematological profiles kurdish population disturbance immunological parameters addition utilization cu+2 supplement effective modality rrms patients may beneficial,0.0
impact motor disability level fatigue adherence therapeutic recommendations patients multiple sclerosis treated immunomodulation int j med sci 2021 aug 27 18 15 36093614 doi 107150 ijms61964 ecollection 2021abstractaim aim study clarify whether motor disability fatiguerelated syndrome affect level compliance therapeutic recommendations methods prospective studies conducted among 165 patients treated drug program treatment multiple sclerosis ms department neurology clinical neuroimmunology regional specialist hospital grudziadz poland research carried method diagnostic survey questionnaire technique use standardized research tools adherence chronic diseases scale acds used assess level compliance therapeutic recommendations expanded disability status scale edss used assess degree disability modified fatigue impact scale mfis used assess degree disability chisquare test shapirowilk test kruskalwallis used results statistical analysis showed relationship p00055 patients motor disability assessed edss scale level compliance therapeutic recommendations assessed acds scale higher patients disability level edss 4565 lower treatment adherence rate conducted research shows average score mfis scale individual levels compliance therapeutic recommendations expressed acds scale respectively low level 383 mfis points medium level 344 mfis points high level 332 mfis points obtained results statistically significant p06098 conclusion found level adherence therapeutic recommendations patients relapsingremitting multiple sclerosis treated immunomodulation study group remained high relationship patients disability level adherence therapeutic recommendationspmid34522188 pmcpmc8436112 doi107150 ijms61964,0.0
plantderived cyclotides modulate opioid receptor signaling j nat prod 2021 jul 26 doi 101021 acsjnatprod1c00301 online ahead printabstractcyclotides plantderived disulfiderich peptides comprising cyclic cystine knot confers remarkable stability thermal proteolytic chemical degradation represent emerging class g proteincoupled receptor gpcr ligands study utilizing screening approach plant extracts pharmacological analysis identified cyclotides carapichea ipecacuanha ligands opioid receptor kor attractive target developing analgesics reduced side effects therapeutics multiple sclerosis ms prompted us verify whether t20k kalata b1 cyclotide clinical development treatment ms able modulate kor signaling t20k bound fully activated kor low m range explored ability t20k allosterically modulate kor coincubation t20k kor ligands resulted positive allosteric modulation functional camp assays altering either efficacy dynorphin a113 potency efficacy u50 488 selective kor agonist respectively addition t20k increased basal response upon cotreatment u50 488 bioluminescence resonance energy transfer assay t20k negatively modulated efficacy u50 488 study identifies cyclotides capable modulating kor highlights potential plantderived peptides opportunity develop cyclotidebased kor modulatorspmid34308635 doi101021 acsjnatprod1c00301,0.0
impact cognitive rehabilitation quality life multiple sclerosis pilot study mult scler j exp transl clin 2021 aug 26 7 3 20552173211040239 doi 101177 20552173211040239 ecollection 2021 julsepabstractbackground cognitive impairment people multiple sclerosis pwms negatively impacts daily function quality life qol prior studies cognitive rehabilitation pwms shown limited benefit many focused cognitive function scores rather qol measures studies using qol metrics primarily evaluated group cognitive rehabilitation may less appropriate due variable cognitive profiles pwms study assesses impact individualized cognitive rehabilitation approach qol msmethods performed retrospective chart review neuroqol assessments done pwms n 12 mean age 479 40 years 75 female 100 white 75 rrms participation individualized compensatory cognitive program used comparison group pwms candidates program participate n 9 mean age 489 44 years 889 female 100 white 667 rrms results pwms participated rehabilitation program saw improvements sleep disturbance 505 555 p 0005 fatigue 525 570 p 0024 anxiety 498 554 p 0011 cognitive function 393 367 p 0049 conclusions individualized compensatory cognitive rehabilitation appears effective improving qol measures pwms cognitive complaints supporting need randomized controlled prospective analysis interventionpmid34471544 pmcpmc8404656 doi101177 20552173211040239,0.0
intestinal permeability circulating cd161+ccr6+cd8+t cells patients relapsingremitting multiple sclerosis treated dimethylfumarate front neurol 2021 aug 26 12683398 doi 103389 fneur2021683398 ecollection 2021abstractbackground changes gutbrain axis recently recognized important components multiple sclerosis ms pathogenesis objectives evaluate effects dmf intestinal barrier permeability mucosal immune responses methods investigated intestinal permeability ip circulating cd161+ccr6+cd8+t cells 25 patients ms met eligibility criteria dimethylfumarate dmf treatment data together clinical mri parameters studied three timepoints baseline therapy one t1 9 months t2 treatment results baseline 16 patients 64 showed altered ip 14 cases 56 showed active mri dmf therapy found expected decrease disease activity mri compared t0 6 25 t1 p 0035 3 25 t2 p 000 reduction percentage cd161+ccr6+cd8+ t cells 16 23 t2 p 0001 effects dmf gut barrier alterations variable without clear longitudinal pattern found significant relationships ip changes drop mri activity p 004 circulating cd161+ccr6+cd8+ t cells p 0023 conclusions gut barrier frequently altered ms cd161+ ccr6+cd8+ t cellsubset shows dynamics correlate disease course therapypmid34512507 pmcpmc8426620 doi103389 fneur2021683398,0.0
clinical spectrum young onset dementia points stochastic origins j alzheimers dis rep 2021 aug 26 5 1 663679 doi 103233 adr210309 ecollection 2021abstractbackground dementia major global health problem search improved therapies ongoing study young onset dementia yod onset prior 65 yearsrepresents challenge owing variety clinical presentations pathology gene mutations advantage investigation yod lack comorbidities complicate clinical picture older adults explore origins yodobjective define clinical diversity yod terms demography range presentations neurological examination findings comorbidities medical history cognitive findings imaging abnormalities structural functional electroencephagraphic eeg data neuropathology geneticsmethods prospective 20year study 240 communitybased patients referred specialty neurology clinics established elucidate nature yodresults alzheimers disease ad n 139 behavioral variant frontotemporal bvftd n 58 common causes mean age onset 565 years ad 1 sd 545 571 years bvftd 1 sd 566 neuropathology showed variety diagnoses multiple sclerosis lewy body disease ftdmnd tdp43 proteinopathy adultonset leukoencephalopathy axonal steroids pigmented glia corticobasal degeneration unexplained small vessel disease autoimmune tcell encephalitis nonamnestic forms ad alternative forms ftd discovered mutations found 11 subjects 11 240 46 apoe genotyping divergent two populationsconclusion multiple kinds yod sporadic observations point stochastic originspmid34632303 pmcpmc8461730 doi103233 adr210309,0.0
bloodspinal cord barrier leakage independent motor neuron pathology als abstractamyotrophic lateral sclerosis als fatal neurodegenerative disease involving progressive degeneration upper lower motor neurons pattern lower motor neuron loss along spinal cord follows pattern deposition phosphorylated tdp43 aggregates bloodspinal cord barrier bscb restricts entry spinal cord parenchyma blood components can promote motor neuron degeneration als evidence barrier breakdown sought quantify bscb breakdown along spinal cord axis determine whether bscb breakdown displays patterning motor neuron loss tdp43 proteinopathy cerebrospinal fluid hemoglobin measured living als patients n 87 control n 236 als potential biomarker bscb bloodbrain barrier leakage cervical thoracic lumbar postmortem spinal cord tissue n 5 control n 13 als immunolabelled semiautomated imaging analysis performed quantify hemoglobin leakage lower motor neuron loss phosphorylated tdp43 inclusion load hemoglobin leakage observed along whole als spinal cord axis severe dorsal gray white matter thoracic spinal cord contrast motor neuron loss tdp43 proteinopathy seen three levels als spinal cord abundant tdp43 deposition anterior gray matter cervical lumbar cord data show leakage bscb occurs life endstage disease regions severe bscb damage tdp43 accumulation abundant suggests bscb leakage tdp43 pathology independent pathologies als,0.0
cxcl13 cxcr5chemokine axis neuroinflammation evidence cxcr5+cd4 t cell recruitment csf background cxc chemokine ligand 13 cxcl13 frequently elevated cerebrospinal fluid csf variety inflammatory central nervous system cns diseases detected meningeal b cell aggregates brain tissues multiple sclerosis patients proposedly recruits b cells inflamed cns besides b cells also follicular helper t tfh cells express cognate receptor cxc chemokine receptor type 5 cxcr5 follow cxcl13 gradients lymphoid tissues highly specialized b cell helper t cells indispensable b cell responses infection vaccination involved autoimmune diseases phenotypically functionally related circulating cxcr5+cd4 t cells occur blood corecruitment inflamed csf feasible unresolvedmethodswe approached question retrospective study including data patients 2017 2019 immune phenotyping data cxcr5 expression csf cxcl13 concentrations available discharge diagnoses csf laboratory parameters retrieved records patients categorized pyogenic aseptic meningoencephalitis n 29 neuroimmunological diseases nimm n 22 noninflammatory neurological diseases nind n 6 anova models spearmans rankorder correlation used group comparisons associations cxcl13 levels immune phenotyping dataresultsin fact intrathecal cxcl13 elevations strongly correlated cxcr5+cd4 t cell frequencies total cohort p 00001 r 059 p 0003 r 054 nimm p 0043 r 044 patients moreover ratio csftoperipheral blood csf pb frequencies cxcr5+cd4 t cells strongly correlated cxcl13 levels total cohort p 0001 r 045 subgroup p 0005 r 050 indicating selective accumulation nimm nind groups differed regard csf cell counts albumin quotient intrathecal igg cxcl13 elevations cxcr5+cd4 t cells higher inflammatory subgroupsconclusionthe observed link intrathecal cxcl13 elevations cxcr5+cd4 t cell frequencies prove suggests recruitment possible professional b cell helpers inflamed csf highlights csf cxcr5+cd4 t cells key target potential missing link poorly understood phenomenon intrathecal b cell antibody responses relevance infection control chronic inflammation cns autoimmunity,0.0
immunologic biomarkers morbidity mortality among hiv patients hospitalised tertiary care hospital brazilian amazon background irregular use antiretroviral therapy art late diagnosis still account large part hivassociated mortality people living hiv plhiv herein describe hivassociated morbidity among hospitalised hiv aids patients advanced immunosuppression assess comorbidities laboratory parameters immunological markers associated mortalitymethodsthe crosssectional study conducted fundao de medicina tropical doutor heitor vieira dourado fmthvd manaus brazil 83 participants aged 12 70 years enrolled convenience within 72 h hospitalisation clinical laboratory data obtained electronic medical records prospectively measured cytokines th1 th2 th17 inflammatory cytokines il8 il1 il12 using cytometric bead array soluble cd14 using inhouse enzymelinked immunosorbent assayresultsthe hiv aids inpatients presented scenario respiratory syndromes prevalent comorbidity almost patients cd4 t counts 350 cells ml mortality rate 205 pulmonary tuberculosis neurotoxoplasmosis oropharyngealesophageal candidiasis prevalent opportunistic infections tb weight loss prevalent hiv aids inpatients died mann whitney analysis showed died higher platelet distribution width pdw admission suggestive platelet activation poisson multivariate analysis showed prevalence tb digestive syndrome increases il8 lactate dehydrogenase ldh associated deathconclusionsthe advanced immunosuppression characterized opportunistic infections presented hiv aids inpatients major factor mortality role platelet activation worse outcomes hospitalisation il8 associated context advanced immunosuppression may promising markers prediction mortality hiv aids patients,0.0
mri ultrahigh field strength highperformance gradients challenges opportunities clinical neuroimaging 7 t beyond eur radiol exp 2021 aug 26 5 1 35 doi 101186 s41747021002162abstractresearch ultrahigh magnetic field strength combined ultrahigh ultrafast gradient technology provided enormous gains sensitivity resolution contrast neuroimaging article provides overview technical advantages challenges performing clinical neuroimaging studies ultrahigh magnetic field strength combined ultrahigh ultrafast gradient technology emerging clinical applications 7t mri stateoftheart gradient systems equipped 300 mt m gradient strength reviewed impact benefits advances anatomical structural functional mri discussed variety neurological conditions finally outlook future directions ultrahigh field mri combined ultrahigh ultrafast gradient technology neuroimaging examinedpmid34435246 doi101186 s41747021002162,0.0
multiple sclerosis reduces synchrony magnocellular pathway plos one 2021 aug 26 16 8 e0255324 doi 101371 journalpone0255324 ecollection 2021abstractmultiple sclerosis ms autoimmune demyelinating disease damages insulation nerve cell fibers brain spinal cord visual system demyelination results robust delay visually evoked potentials veps even absence overt clinical symptoms blurred vision veps therefore offer avenue early diagnosis monitoring disease progression potentially insight differential impairment specific pathways primary hypothesis visual stimuli driving magno parvo koniocellular pathways lead differential effects pathways differ considerably terms myelination experimental tests hypothesis however led conflicting results groups reported larger latency effects chromatic stimuli others found equivalent effects across stimulus types reasoned lack pathway specificity least part attributed relatively coarse measure pathway impairment afforded latency vep hypothesized network synchrony offer sensitive test pathway impairments test hypothesis analyzed synchrony occipital electroencephalography eeg signals presentation visual stimuli designed bias activity one three pathways specifically quantified synchrony occipital eeg using two graphtheoretic measures functional connectivity characteristic path length l measure longrange connectivity clustering coefficient cc measure shortrange connectivity main finding l cc smaller ms group controls notably change functional connectivity limited magnocellular pathway effect sizes hedges g 089 l 126 cc measured magno stimuli together l cc define smallworld nature network finding can summarized reduction smallworldness magnocellular network speculate reduced efficiency information transfer associated reduction smallworldness underlie visual deficits ms relating measures differential diagnoses disease progression important avenue future workpmid34437558 doi101371 journalpone0255324,1.0
neuroimaging 7 t ready clinical transition eur radiol exp 2021 aug 26 5 1 37 doi 101186 s41747021002340abstractin last 20 years ultrahigh field uhf magnetic resonance imaging mri become outstanding research tool study human brain 90 scanners installed today worldwide recent clearances regulatory bodies usa europe 7t clinical systems set ground transition pure research applications research clinical use systems today ufh neuroimaging demonstrating clinical value given importance topic preclinical scientists clinical neuroradiologists european radiology experimental launching thematic series entitled 7t neuro mri research clinic consisting peerreviewed articles invited spontaneously submitted topics selected guest editors describing state art uhf mri neuroimaging across different pathologies well related clinical applications editorial discuss challenges related clinical use 7t scanners strengths weaknesses clinical imaging uhfpmid34435257 doi101186 s41747021002340,0.0
circrnas regulatory roles cancers abstractcircular rnas circrnas novel type noncoding rnas ncrnas covalently closed circular structure resulting premrna back splicing via spliceosome ribozymes can classified differently accordance different criteria circrnas abundant conserved stable can used diagnostic markers various diseases targets develop new therapies various functions circrnas including sponge mir proteins role scaffolds templates translation regulators mrna translation stability without m7g cap polya tail circrnas can still degraded several ways including rnase l agodependent agoindependent degradation increasing evidence indicates circrnas can modified n6 methylation m6a many aspects biogenesis nuclear export translation degradation addition proved play regulatory role progression various cancers recently methods detecting circrnas high sensitivity specificity also reported review presents detailed overview circrnas regarding biogenesis biomarker functions degradation dynamic modification well regulatory roles various cancers particularly summarized detail biogenesis circrnas regulation circrnas m6a modification mechanisms circrnas affect tumor progression respectively moreover existing circrna detection methods characteristics also mentioned,0.0
higher proportion erminimmunopositive oligodendrocytes areas remyelination plos one 2021 aug 26 16 8 e0256155 doi 101371 journalpone0256155 ecollection 2021abstractincomplete remyelination frequent multiple sclerosis ms lesions established marker recent remyelination investigated role oligodendrocyte myelin protein ermin de remyelination cuprizone cpz mouse model ms density ermin+ oligodendrocytes brain significantly decreased one week cpz exposure p 002 relative proportion ermin+ cells compared cells positive latestage oligodendrocyte marker nogoa increased onset remyelination corpus callosum p 002 density erminpositive cells increased corpus callosum cpzphase extensive remyelination p 00001 ms density ermin+ cells higher remyelinated lesion areas compared nonremyelinated areas white p 00001 grey matter p 00001 compared normalappearing white matter p 0001 ermin immunopositive cells mslesions immunopositive earlystage oligodendrocyte markers o4 o1 subpopulation immunopositive nogoa data suggest relatively higher proportion ermin immunopositivity oligodendrocytes compared nogoa indicates recent ongoing remyelinationpmid34437581 doi101371 journalpone0256155,1.0
psychoeducational interventions caregivers persons multiple sclerosis protocol randomized trial jmir res protoc 2021 aug 26 10 8 e30617 doi 102196 30617abstractbackground approximately 1 million people living multiple sclerosis united states half receive informal unpaid care support family friends caregivers caregivers report high levels stress anxiety negative emotions researchers conducted psychoeducational interventions caregiversobjective paper presents protocol randomized clinical trial aims test efficacy two interventions improving stress anxiety depression negative emotions caregivers persons multiple sclerosismethods participants included selfidentified family friend caregiver person multiple sclerosis data collection began april 2021 expected continue november 2021 participants will randomized receive either websiteonly websitecoaching intervention delivered 6 weeks data will collected baseline 6 weeks baseline delivery intervention 6 weeks laterresults protocol approved institutional review board case western reserve university january 21 2021 protocol 20201484 may 2021 66 participants enrolledconclusions findings will implications identifying efficacy two types interventions developed caregivers persons multiple sclerosis reduce negative psychological outcomes associated caregivingtrial registration clinicaltrialsgov nct04662008 http clinicaltrialsgov ct2 show nct04662008international registered report identifier irrid derr1102196 30617pmid34435971 doi102196 30617,0.0
research interrupted impact covid19 pandemic multiple sclerosis research field rehabilitation quality life mult scler j exp transl clin 2021 aug 26 7 3 20552173211038030 doi 101177 20552173211038030 ecollection 2021 julsepabstractbackground covid19 pandemic likely negative impact rehabilitation quality life qol research multiple sclerosis ms method explored perceived barriers research among 87 researchers representing 18 countries prior since covid19results wilcoxon signedrank test found significantly researchers reported experiencing barriers research since onset pandemic compared precovid19 p 001 78 respondents reporting least barriers since covid19 commonlycited barriers related participant access n 38 interruptions delays projects n 19 although gender differences found number barriers reported female respondents likely cite time competing demands barriers research females also likely perceive negatively impacted pandemic compared genders p 007 conclusions implications future landscape rehabilitation research ms discussedpmid34471543 pmcpmc8404642 doi101177 20552173211038030,0.0
tetravalent influenza vaccine associated neuroaxonal damage multiple sclerosis patients front immunol 2021 aug 26 12718895 doi 103389 fimmu2021718895 ecollection 2021abstractbackground efficacy vaccines disease activity linked immunization major concerns among people multiple sclerosis pwms objective assess antibody responses seasonal influenza antigens vaccineassociated neuroaxonal damage utilizing serum neurofilament light chain snfl pwms receiving dimethyl fumarate dmf methods prospective study 2020 2021 seasonal tetravalent influenza vaccine administered 20 pwms treated dmf 15 healthy controls hcs primary endpoints responder rate strainspecific antibody production seroconversion significant 4fold increase influenzaantibody titers 2 4 strains 30 days postvaccination changes snfl levelsresults patients treated dmf fulfilled responder criteria immunization compared 53 controls however higher proportions hcs already influenzaantibody titers 140 baseline 53 vs 41 p 0174 snfl levels comparable among groups baseline increase 34 days vaccination addition clinical radiological disease reactivation foundconclusion dmftreated patients mount adequate humoral immune response influenza vaccines within limits small cohort investigated data suggest influenza immunization associated clinical subclinical disease reactivationpmid34512642 pmcpmc8428149 doi103389 fimmu2021718895,0.0
tuberous sclerosis complexlymphangioleiomyomatosis involving several visceral organs case report world j clin cases 2021 aug 26 9 24 70857091 doi 1012998 wjccv9i247085abstractbackground lymphangioleiomyomatosis lam rare cystic lung disease characterized proliferation metastasis infiltration smooth muscle cells lung tissues can associated tuberous sclerosis complex tsc disorder tsc variable expression great phenotypic variabilitycase summary 32yearold chinese woman history multiple renal angioleiomyolipoma presented productive cough persisting 2 wk highresolution chest computed tomography revealed interstitial changes multiple pulmonary bullae bilateral pulmonary nodules multiple fat density areas inferior mediastinum conventional contrast ultrasonography revealed multiple high echogenic masses liver kidneys retroperitoneum inferior mediastinum masses diagnosed angiomyolipomas pathology thoracoscopic lung biopsy confirmed lam furthermore highthroughput genome sequencing peripheral blood dna confirmed presence heterozygous mutation c1831ct parg611trp tsc2 gene patient diagnosed tsclamconclusion highlight rare case tsclam first report mediastinum lymphangioleiomyoma associated tsclampmid34540963 pmcpmc8409179 doi1012998 wjccv9i247085,0.0
clinical paraclinical biomarkers hitches assess conversion secondary progressive multiple sclerosis systematic review front neurol 2021 aug 26 12666868 doi 103389 fneur2021666868 ecollection 2021abstractconversion secondary progressive sp course decisive factor longterm prognosis relapsing multiple sclerosis ms generally considered clinical equivalent progressive msassociated neuroaxonal degeneration evidence accumulating inflammation neurodegeneration present along continuum pathologic processes phases ms inflammation prominent feature early stages quality changes relative importance disease course decreases neurodegenerative processes prevail ongoing disease consequently antiinflammatory diseasemodifying therapies successfully used relapsing ms ineffective spms whereas specific treatment latter increasingly focus ms research therefore prevention also anticipatory diagnosis spms crucial importance problem currently spms diagnosis exclusively based retrospectively assessing increase overt physical disability usually past 612 months inevitably results delay diagnosis 3 years resulting periods uncertainty thus making early therapy adaptation prevent spms conversion impossible hence urgent need reliable objective biomarkers prospectively predict define spms conversion review current evidence clinical parameters magnetic resonance imaging optical coherence tomography measures serum cerebrospinal fluid biomarkers context msassociated neurodegeneration spms conversion ultimately discuss necessity multimodal approaches order approach objective definition prediction conversion spmspmid34512500 pmcpmc8427301 doi103389 fneur2021666868,0.0
drug neurofilament levels serum breastmilk women multiple sclerosis exposed natalizumab pregnancy lactation front immunol 2021 aug 26 12715195 doi 103389 fimmu2021715195 ecollection 2021abstractobjective determine transfer monoclonal antibody natalizumab breastmilk evaluate drug serum neurofilament light chain s nfl levels natalizumab exposed pregnancies lactation periodsmethods eleven women relapsing remitting multiple sclerosis treated natalizumab pregnancy lactation included study breastmilk samples collected 302 days delivery analyzed natalizumab concentration nfl additionally maternal drug levels snfl determined preconceptually trimester delivery postpartum clinical radiological disease activity systemically assessed across pregnancy postpartum periodresults mean average natalizumab concentration breast milk low 006 g ml standard deviation sd 005 eight patients provided serial breastmilk samples estimated mean absolute infant dose 0007 mg kg d sd 0005 relative infant dose rid metric comparing infant maternal drug exposure low well mean 004 sd003 patients maximum concentration breast milk one eight days infusion pregnancy associated nonsignificant decline median natalizumab serum concentration patients exposed natalizumab prior n10 pregnancy n11 kept free disease activity gestation pregnancy associated low snfl levels patients treated natalizumab prior pregnancy postpartum period linked transient snfl increase patients without evidence clinical radiological disease activity nfl detectable majority breastmilk samples median concentration 17 pg ml range 0004181 conclusion determined transfer natalizumab breastmilk rid far threshold concern 10 studies including childhood development assessment needed order gain safety data natalizumabexposed breastfeeding snfl assessment might useful adjunct monitor silent disease activity therapeutic response pregnancy postpartum period however investigations regarding transient postpartum snfl increases required determine association parturition per se silent disease activity people multiple sclerosispmid34512637 pmcpmc8426350 doi103389 fimmu2021715195,0.0
efficacy mesenchymal stem cell therapies rodent models multiple sclerosis updated systematic review metaanalysis front immunol 2021 aug 26 12711362 doi 103389 fimmu2021711362 ecollection 2021abstractstudies demonstrated potential mesenchymal stem cell msc administration promote functional recovery preclinical studies multiple sclerosis ms yet effects mscs remyelination poorly understood wished evaluate therapeutic effects mscs functional histopathological outcomes ms therefore undertook updated systematic review metaanalysis preclinical data msc therapy ms searched mainstream databases inception july 15 2021 interventional studies therapy using nave mscs vivo rodent models ms included study clinical score extracted functional outcome remyelination measured histopathological outcome eightyeight studies published 2005 2021 met inclusion criteria results revealed overall positive effect mscs functional outcome standardized mean difference smd 199 95 confidence interval ci 232 165 p 0000 mscs promoted remyelination smd 231 95 ci 284 179 p 0000 significant heterogeneity among studies observed altogether metaanalysis indicated msc administration improved functional recovery promoted remyelination prominently rodent models mspmid34512632 pmcpmc8427822 doi103389 fimmu2021711362,1.0
genderrelated differences prodromal multiple sclerosis characteristics 7year observation study j clin med 2021 aug 26 10 17 3821 doi 103390 jcm10173821abstractincreasing evidence supports observation multiple sclerosis ms preclinical period various prodromal signs symptoms frequently represented patients confirmed ms many years later considering apparent gender differences incidence clinical course ms remains unclear whether reflected prodromal symptom features study aimed compare broad spectrum prodromal signs symptoms males females 7year period definite diagnosis ms data came central register national payer services financed public healthcare system poland covered 7year period patient health record claims 2009 2016 following groups symptoms significant women musculoskeletal p 0001 ophthalmic p 0001 laryngological p 0001 digestive system p 0001 urinary tract p 0001 mental p 0001 cardiovascular p 0001 complaints headaches p 0001 also weak correlation head injuries p 003 dermatological reproductive system complaints appear significant p 005 males following groups symptoms significant musculoskeletal p 0001 ophthalmic p 0001 laryngological p 0007 cardiovascular system symptoms p 0001 headaches p 0001 interestingly reproductive system problems overrepresented male population p 0008 significant correlation ms risk dermatological digestive urinary mental complaints similarly head injuries significant results shed light wellknown differences epidemiological clinical characteristics sexes multiple sclerosis show differences prodromal complaints ms onsetpmid34501269 doi103390 jcm10173821,0.0
immunopathogenesis proposed clinical score identifying kelchlike protein11 encephalitis brain commun 2021 aug 26 3 3 fcab185 doi 101093 braincomms fcab185 ecollection 2021abstractin study report clinical features kelchlike protein 11 antibodyassociated paraneoplastic neurological syndrome design validate clinical score facilitate identification patients tested kelchlike protein 11 antibodies examine detail nature immune response brain tumour samples better characterization immunopathogenesis condition presence kelchlike protein 11 antibodies retrospectively assessed patients referred french reference center paraneoplastic neurological syndrome autoimmune encephalitis antibodynegative paraneoplastic neurological syndrome limbic encephalitis n 105 cerebellar degeneration n 33 ii antibodypositive paraneoplastic neurological syndrome ma2ab encephalitis n 34 antibodies targeting nmethyldaspartate receptor encephalitis teratoma n 49 additionally since 1 january 2020 patients prospectively screened kelchlike protein 11 antibodies new usual clinical practice overall kelchlike protein 11 antibodies detected 11 patients 11 11 100 male median range age 44 3579 years 9 antibodynegative paraneoplastic neurological syndrome cohort 1 antibodypositive ma2ab cohort 1 additional prospectively detected patient patients manifested cerebellar syndrome either isolated 4 11 36 part multisystem neurological disorder 7 11 64 additional core syndromes limbic encephalitis 5 11 45 myelitis 2 11 18 severe weight loss 7 11 64 hearing loss tinnitus 5 11 45 common rarer neurologic manifestations included hypersomnia seizures 2 11 18 two patients presented phenotypes resembling primary neurodegenerative disorders progressive supranuclear palsy flail arm syndrome respectively associated cancer found 9 11 82 patients commonly 7 9 78 spontaneously regressed burnedout testicular germ cell tumour newly designed clinical score match score male ataxia testicular cancer hearing alterations cutoff 4 successfully identified patients kelchlike protein 11 antibodies sensitivity 78 specificity 99 pathological findings three testicular tumours three lymph node metastases testicular tumours one brain biopsy showed presence tcell inflammation resulting antitumour immunity testis one chronic exhausted immune responsedemonstrated immune checkpoint expressionin metastases brain conclusion findings suggest kelchlike protein 11 antibody paraneoplastic neurological syndrome homogeneous clinical syndrome detection can facilitated using match score pathogenesis probably tcell mediated stages inflammation different testis metastases brainpmid34557666 pmcpmc8453430 doi101093 braincomms fcab185,0.0
neurofilament light heterogeneity disease progression amyotrophic lateral sclerosis development validation prediction model improve interventional trials background interventional trials amyotrophic lateral sclerosis als suffer heterogeneity disease considerably reduces statistical power asked blood neurofilament light chains nfl used anticipate disease progression increase trial powermethodsin 125 patients als three independent prospective studiesone observational study two interventional trialswe developed externally validated multivariate linear model predicting disease progression measured monthly decrease als functional rating scale revised alsfrsr score trained prediction model observational study tested predictive value following parameters assessed diagnosis nfl levels sex age site onset body mass index disease duration alsfrsr score monthly alsfrsr score decrease since disease onset applied resulting model two study cohorts assess actual utility interventional trials analyzed impact trial power mixedeffects models compared performance nfl model two currently used predictive approaches anticipate disease progression using alsfrsr decrease threemonth observational period leadin since disease onset frs resultsamong parameters provided nfl levels p 0001 interaction site onset p 001 contributed significantly prediction forming robust nfl prediction model r 067 model application trial cohorts confirmed applicability revealed superiority leadin frsbased approaches nfl model improved statistical power 61 22 95 confidence intervals 5466 729 conclusionthe use nflbased prediction model compensate clinical heterogeneity als significantly increase trial powernct00868166 registered march 23 2009 nct02306590 registered december 2 2014,0.0
glialspecific deletion med12 results rapid hearing loss via degradation stria vascularis mediator protein complex subunit 12 med12 core component basal transcriptional apparatus plays critical role development many tissues mutations med12 associated xlinked intellectual disability syndromes hearing loss however role nervous system function remains undefined show temporal conditional deletion med12 astrocytes adult cns results regionspecific alterations astrocyte morphology surprisingly behavioral studies revealed rapid hearing loss adult deletion med12 confirmed complete abrogation auditory brainstem responses cellular analysis cochlea revealed degeneration stria vascularis conjunction disorganization basal cells adjacent spiral ligament downregulation key cell adhesion proteins physiologic analysis revealed early changes endocochlear potential consistent strialspecific defects together studies reveal med12 regulates auditory function adult preserving structural integrity stria vascularissignificance statement mutations mediator protein complex subunit 12 med12 associated xlinked intellectual disability syndromes hearing loss using temporalconditional genetic approaches cns glia found loss med12 results severe hearing loss adult animals rapid degeneration stria vascularis study describes first animal model recapitulates hearing loss identified med12related disorders provides new system examine underlying cellular molecular mechanisms med12 function adult nervous system,0.0
causes death effect noncancerspecific death rates overall survival adult classic hodgkin lymphoma populatedbased competing risk analysis background improved prognosis classic hodgkin lymphoma chl accompanied elevated risks noncancerspecific death noncsd aim study verify occurrence noncsd effect rates overall survival among adult patients chlmethodsto ensure sufficient followup time analyzed retrospective data patients aged 20 years chl diagnosed 1983 2005 surveillance epidemiology end results seer database logistic regression applied analyze noncsd occurrence relation factors using finegrays method calculated cumulative incidences csd noncsd stacked cumulative incidence plots ratio noncsd causes death applied evaluate effect noncsd rates overall survival finally analyzed longterm mortality cox proportional hazard regression analysis competing risk regression analysis emphasize appropriate model survival patients chlresultsamong 18 518 patients included 3768 cases csd 203 3217 noncsd 174 older age earlier period male sex unmarried status mixed cellularity mc lymphocytedepletion ld histological subtype patients received radiotherapy rt associated noncsd according binary logistic analysis cumulative incidence noncsd exceeded csd approximately 280 months followup common causes noncsds cardiovascular disease subsequent primary neoplasms infectious diseases accidents suicide cox proportional hazards model patients black unmarried advanced stage underwent chemotherapy ct alone greater risk mortality white patients married early stage underwent combined modality populations also found greater risk csd competing risk model risk noncsd differ significantly according race marital status patients earlystage disease underwent rt found higher risk noncsd insteadconclusionslymphoma cause death patients died noncsd unusual patients chl monitored closely signs cardiovascular disease malignant tumors rates overall survival patients diminished noncsd competing risk model suitable establishing prognosis cox proportional hazards model,0.0
effect different visual presentations comprehension prognostic information systematic review background understanding prognostic information can help patients know may happen health time make informed decisions however communicating prognostic information well can challengingpurposeto conduct systematic review identify synthesize research evaluated visual presentations communicate quantitative prognostic information patients publicdata sourcesmedline embase cinahl psycinfo eric cochrane central register controlled trials central inception december 2020 forward backward citation searchstudy selectiontwo authors independently screened search results assessed eligibility eligible studies required quantitative design comparison least one visual presentation another presentation quantitative prognostic information primary outcome comprehension presented information secondary outcomes preferences satisfaction presentations viewed behavioral intentionsdata extractiontwo authors independently assessed risk bias extracted datadata synthesiseleven studies randomized trials identified grouped studies according presentation type evaluated bar graph versus pictograph 3 studies difference comprehension groups survival vs mortality curves 2 studies difference one study higher comprehension survival curve group another study tabular format versus pictograph 4 studies 2 studies reported similar comprehension groups 2 found higher comprehension pictograph groups tabular versus free text 3 studies 2 studies found difference groups 1 found higher comprehension tabular grouplimitationsheterogeneity visual presentations outcome measures precluding metaanalysisconclusionsno visual presentation appears consistently superior communicate quantitative prognostic information,0.0
editors welcome september 2021 first like boast latest impact factor now risen 439 highest ever attained reflects continuing improvement article quality measured independently clarivate takes account number times articles cited previous two years currently 2020 measure influenced chiefly reviews original articles editorials case reports letters editor partly creation year new sister journal neuroimmunology reports longer accept casereports submitted will given option transfer article neuroimmunology reports care one chief editors michael levy,0.0
risk assessment progressive multifocal leukoencephalopathy multiple sclerosis patients 1 year ocrelizumab treatment viruses 2021 aug 25 13 9 1684 doi 103390 v13091684abstractbackground progressive multifocal leukoencephalopathy pml caused jc virus main limitation use disease modifying therapies treatment multiple sclerosis ms methods assess pml risk course ocrelizumab urine blood samples collected 42 ms patients baseline t0 6 t2 12 months t4 beginning therapy jcpyvdna extraction quantitativepcr qpcr performed moreover assessment jcvserostatus obtained arrangements analysis noncoding control region nccr viral capsid protein 1 vp1 carried outresults qpcr revealed jcpyvdna urine selected time points jcpyvdna detected plasma t4 t0 t4 jc viral load urine detected increased two logarithms significantly higher compared viremia nccr urine archetypal plasmatic nccr displayed deletion duplication point mutations vp1 showed s269f substitution involving receptorbinding region antijcv index igm titer found statistically decrease ocrelizumab treatmentconclusions ocrelizumab jcpyvdna positive patients safe determine pml cases combined monitoring ocrelizumabs effects jcpyv pathogenicity host immunity might offer complete insight towards predicting pml riskpmid34578264 doi103390 v13091684,0.0
alterations gut mycobiome patients ms background mycobiome fungal component gut microbiome implicated several autoimmune diseases however role ms studied methods casecontrol observational study performed sequencing characterised gut mycobiome people ms pwms healthy controls baseline six months findings mycobiome significantly higher alpha diversity intersubject variation pwms controls saccharomyces aspergillus overrepresented pwms saccharomyces positively correlated circulating basophils negatively correlated regulatory b cells aspergillus positively correlated activated cd16+ dendritic cells pwms different mycobiome profiles defined mycotypes associated different bacterial microbiome immune cell subsets blood initial treatment dimethyl fumarate common immunomodulatory therapy also fungicidal activity cause uniform gut mycobiome changes across pwms interpretation alteration gut mycobiome pwms compared healthy controls study required assess causal association mycobiome ms direct indirect interactions bacteria autoimmunity funding work supported washington university st louis institute clinical translational sciences funded part grant number # ul1 tr000448 national institutes health national center advancing translational sciences clinical translational sciences award zhou y piccio l lovettracke tarr pi r01 ns10263304 zhou y piccio l leon harriet felman fund human ms research piccio l cross ah cantoni c supported national ms society career transition fellowship ta180531003 donations whitelaw terry jr valerie terry fund ghezzi l supported italian multiple sclerosis society research fellowship fism 2018 b 1 national multiple sclerosis society postdoctoral fellowship fg 190734474 anne cross supported manny rosalyn rosenthaldr john l trotter ms center chair neuroimmunology barnesjewish hospital foundation content solely responsibility authors necessarily represent official views national institutes health,0.0
discordant humoral t cell immune responses sarscov2 vaccination people multiple sclerosis anticd20 therapy medrxiv 2021 aug 252021082321262472 doi 101101 2021082321262472 preprintabstractbackground sphingosine1phosphate receptor s1p modulators anticd20 therapies impair humoral responses sarscov2 mrna vaccines whether disease modifying therapies dmts multiple sclerosis ms also impact t cell immune response vaccination unknownmethods 101 people ms measured humoral responses via immunoassay measure igg covid19 spike s1 glycoprotein serum also measured t cell responses using fluorospot assay interferon gamma ifn mabtech sweden using cryopreserved rested pbmcs incubated crpmi 1g ml pooled peptides spanning entire spike glycoprotein genscript 2 pools 158 peptides plates read aid ispot spectrum determine number spot forming cells sfc 10 6 pbmcs tested differences immune responses across dmts using linear modelsfindings humoral responses detected 22 39 564 participants anticd20 59 63 936 participants dmts subset immune cell phenotyping n88 87 t cell responses detected 76 88 86 including 32 33 969 participants anticd20 therapies anticd20 therapies associated increase ifn sfc counts relative dmt dmts anticd20 vs dmt 4259 higher 95ci 1096 12066 higher p0001 anticd20 vs dmts 2896 95ci 859 7166 higher p0001 interpretation identified robust t cell response individuals anticd20 therapies despite reduced humoral response sarscov2 vaccination follow studies needed determine translates protection covid19 infectionpmid34462762 pmcpmc8404904 doi101101 2021082321262472,0.0
influence glutenfree diet healthrelated quality life individuals celiac disease background adherence glutenfree diet gfd food insecurity fi may influence healthrelated quality life hrqol individuals celiac disease cd study aimed investigate association adherence gfd fi hrqol individuals cdmethodsthis crosssectional study included 97 adults mean age 34 9 years diagnosed cd participants gfd 6 months sociodemographic characteristics medical history assessed adherence gfd fi hrqol assessed using validated questionnairesresultsmost participants 73 adhered gfd 62 experiencing fi individuals cd faced difficulty accessing gf foods due high cost 90 limited availability 79 mean overall hrqol score 60 scores physical mental health domains 69 47 respectively adherence gfd significantly associated fi p 002 association adherence gfd hrqol measures p 005 participants facing fi lower scores emotional wellbeing mental health domains overall hrqol p 005 conclusionsthe findings present study demonstrate fi influences adherence gfd fi associated hrqol terms emotional wellbeing mental health,0.0
microarraybased analysis renal complement components reveals therapeutic target lupus nephritis background screening abnormal pathways complement components kidneys patients lupus nephritis ln nzb w mice may help identify complementrelated therapeutic targets lnmethodskegg go enrichment assays used analyze kidney microarray data ln patients nzb w mice immunohistochemistry immunofluorescence assays used measure renal expression complementrelated proteins tgf1 cytokines measured using rtqpcr elisaresultswe screened renal pathogenic pathways present ln patients nzb w mice selected complement activation pathway study results indicated greater renal expression c1qa c1qb c3 c3ar1 c5ar1 mrna protein levels c3 appeared key factor ln renal signaling downstream c1 inhibited significant correlations expression tgf1 c3 analysis primary cell cultures indicated tgf1 promoted expression c3 tgf1 antagonist decreased levels c3 c3ar tgf1 inhibition significantly inhibited deposition complementrelated factors kidneys nzb w miceconclusionsat onset ln significant increases renal levels c3 complement pathwayrelated factors patients ln nzb w mice c3 may lead albuminuria participate pathogenesis ln tgf1 promotes c3 synthesis tgf1 inhibition may block progression ln inhibiting synthesis c3 complement components,0.0
menactrims practice guideline covid19 vaccination patients multiple sclerosis summarypatients multiple sclerosis ms vaccinated covid19all covid19 vaccines effective appear carry additional risk patients ms patients ms get covid19 vaccine soon becomes available risks covid19 disease outweigh potential risks vaccineeven vaccinated patients ms continue practice standard recommended precautions covid19 wearing face mask social distancing washing handsthere evidence patients ms higher risk complications mrna nonreplicating viral vector inactivated virus protein covid19 vaccines compared general populationcovid19 vaccines safe use patients ms treated diseasemodifying therapies dmts effectiveness vaccination may affected dmts yet protection still providedfor certain dmts may consider coordinating timing vaccine timing dmt dose increase vaccine efficacy,0.0
evaluation diagnosis treatment practices brazilian neurologists among patients multiple sclerosis abstract background recent changes diagnostic criteria multiple sclerosis ms new medications major impact way specialists manage disease objective investigate factors considered brazilian neurologists managing ms identify contribute diagnosis treatment methods potential participants selected steering committee ms experts developed survey ms specialists included study neurologists completed neuroimmunology fellowship treating 30 ms patients links online questionnaire distributed march 2019 january 2020 questionnaire composed sections hypothetical ms scenarios results neurologists 13 brazilian states responded survey n 94 clinically isolated syndrome cis scenario respondents agreed treat patients high risk ms diagnosis whereas radiologically isolated syndrome ris half respondents opted treat even among highrisk patients cases lowactivity relapsingremitting ms rrms choice treatment distributed among interferon beta glatiramer acetate teriflunomide changed fingolimod natalizumab rrms severity increased topics disagreement found included practices regarding use diseasemodifying therapy dmt pregnant patients washout period required dmts conclusions study enabled identification areas agreement disagreement ms treatment among brazilian neurologists can used update future protocols improve patient management,0.0
intrathecal antibody production epsteinbarr herpes simplex neurotropic viruses autoimmune encephalitis neurol neuroimmunol neuroinflamm 2021 aug 24 8 6 e1062 doi 101212 nxi0000000000001062 print 2021 novabstractbackground objectives neurotropic viruses suspected play role pathogenesis autoimmune diseases cns association epsteinbarr virus ebv multiple sclerosis ms group autoimmune encephalitis ae linked antibodies neuronal cell surface proteins cns infection herpes simplex virus can trigger antinmda receptor nmdar encephalitis similar mechanism ebv neurotropic viruses postulated investigate previous viral infections cns intrathecally produced virusspecific antibody synthesis determined patients aemethods antibodyspecific indices ais ebv measles rubella varicella zoster herpes simplex virus cytomegalovirus determined 27 patients ae antinmdar encephalitis n 21 lgi1 encephalitis n 6 2 control groups comprising 30 patients ms 21 patients noninflammatory cns diseases nind sex age matchedresults intrathecal synthesis antibodies ebv found 5 27 19 patients ae 2 30 7 patients ms patients also least 1 additional elevated virusspecific ai contrast none patients nind elevated virusspecific ai detecteddiscussion intrathecally produced antibodies ebv can found patients ae ms together antibodies different neurotropic viruses evidence antibodies result polyspecific immune response similar yet distinct ms response rather elapsed infection cnspmid34429365 doi101212 nxi0000000000001062,0.0
melanoma cell adhesion molecule expressing helper t cells cns inflammatory demyelinating diseases neurol neuroimmunol neuroinflamm 2021 aug 24 8 6 e1069 doi 101212 nxi0000000000001069 print 2021 novabstractbackground objective elucidate relationship melanoma cell adhesion molecule mcam expressing lymphocytes pathogenesis cns inflammatory demyelinating diseases idds methods patients multiple sclerosis ms n 72 neuromyelitis optica spectrum disorder nmosd n 29 included analyzed frequency absolute numbers mcam+ lymphocytes memory helper t mth cells naive helper t cells cd8+ t cells b cells peripheral blood pb csf patients ms nmosd treated without diseasemodifying drugs dmds steroids using flow cytometryresults frequency mcam+ cells higher mth cell subset lymphocyte subsets significant increase frequency absolute number mcam+ mth cells observed pb patients nmosd whereas increase observed pb patients ms frequency csf mcam+ mth cells higher relapsing patients ms nmosd control group although difference frequencies mcam+ lymphocytes among dmdtreated groups fingolimod decreased absolute number mcam+ lymphocytesdiscussion mcam+ mth cells elevated csf relapsing patients ms pb csf patients nmosd results indicate mcam contributes pathogenesis ms nmosd different mechanisms mcam therapeutic target cns idds study needed elucidate underlying mechanism mcam cns idd pathogenesispmid34429366 doi101212 nxi0000000000001069,1.0
giant cell tumors mobile spine invasion adjacent vertebrae unusual imaging finding background giant cell tumors mobile spine invasion adjacent vertebrae ignored imaging findingmethodsnine patients giant cell tumors mobile spine invasion adjacent vertebrae confirmed pathology enrolled eight patients pure giant cell tumors gcts one patient also aneurysmal bone cyst patients underwent conventional computed tomography threedimensional reconstruction conventional magnetic resonance imaging seven patients also underwent postcontrast magnetic resonance imagingresultsall patients showed gcts mobile spine arose vertebral body extended vertebral arch tumors showed softtissue attenuation evidence mineralized matrix pathological fracture seen five patients margin original tumor showed partial sclerosis four patients involved adjacent vertebral body sclerotic rim two patients tumors showed homogeneous similar signal intensity normal spinal cord t1wi t1weighted image five patients cystic area tumors hyperintense t2wi remaining four patients one patient showed hemorrhage hyperintense t1wi solid components gcts show marked enhancement cases cystic area tumors observed without enhancement contrastenhanced images four patients bone destruction adjacent vertebral body showed homogeneous signal t1wi t2wi marked enhancement contrastenhanced imagesconclusionsgiant cell tumors mobile spine invasion adjacent vertebrae unusual imaging finding radiologists familiar imaging characteristic,0.0
relationship effects vitamin d metabolic syndrome systematic review cureus 2021 aug 24 13 8 e17419 doi 107759 cureus17419 ecollection 2021 augabstractmetabolic syndrome mets persistent public health problem united states us due increasing prevalence positive correlation type2 diabetes t2dm cardiovascular disease cvd according national cholesterol education programs adult treatment panel iii ncepatp iii criteria mets six main components obesity dyslipidemia raised blood pressure bp insulin resistance ir glucose intolerance proinflammatory state prothrombotic state vitamin d vit d regulates absorption calcium phosphorus thus universally accepted essential vitamin bone strength well facilitator immune system function vit d also shown reduce risks cvd multiple sclerosis developing seasonal flu conducted systematic review identify general association vit d level mets highlight specific associations vit d level individual components mets finally explore effects vit d supplementation component mets paper reviewed 14 recent studies investigating relationships vit d mets components mets review seven studies confirmed significant association vit d mets whole four five observational studies reviewed support vit d level significantly associated following components mets obesity bmi dyslipidemia bp insulin glucose metabolism discover significant relationship vit d level mets components review seven additional randomized clinical trials rct based studies suggest vit d supplementation significant effects bp abdominal obesity insulin glucose metabolismpmid34589329 pmcpmc8460559 doi107759 cureus17419,0.0
secondary progressive multiple sclerosis new insights neurology 2021 jun 4101212 wnl0000000000012323 doi 101212 wnl0000000000012323 online ahead printabstractin cases multiple sclerosis ms begins relapsingremitting course followed insidious disability worsening independent clinically apparent relapses termed secondary progressive multiple sclerosis smps major differences exist relapsingremitting ms rrms spms especially regarding therapeutic response treatment review provides overview pathology differentiation challenges diagnosis treatment spms emphasize criticality conversion relapsingremitting secondary progressive disease course conversion evidence disability progression also recently treatments effectively reduced disability progression relapsing ms proven effective spms clear clinical imaging immunological pathological criteria marking transition rrms spms yet established early identification spms will require tools together use appropriate treatments may result better longterm outcomes population patients spmspmid34088878 doi101212 wnl0000000000012323,0.0
grieving disrupted biography interpretative phenomenological analysis exploring barriers use mindfulness neurological injury impairment background mindfulness demonstrated strong utility enhancing selfmanagement health outcomes chronic illness however sensationfocused mindfulness techniques may appropriate clinical populations neurological injury study aimed identify expert mindfulness teachers sensory loss impairment naturalistically adapt experience mindfulness aimed highlight rationale barriers mindfulness practice living sensory lossmethodsa qualitative semistructured interview design used analysed via interpretative phenomenological analysis ipa eight 5 females 3 males mindfulness teachers neurological injury recruited via national registry mindfulness health teachers interviews range 5093 min completed transcribed verbatim analysed idiographically descriptive linguistic conceptual themes crosscase analysis completedresultstwo superordinate themes identified 1 overcoming disrupted biography 2 proactive selfmanagement themes considered challenge reconciling grief past health status present reality living sensory loss due spinal cord injury multiple sclerosis functional neurological disorder mindfulness experienced method proactive choices made maintain control autonomy health reducing perceptions suffering psychological distress cognitive reactivity ruminationconclusionsmindfulness found support selfmanagement health neurological injury impairment mindfulness meditation presented initial challenge trauma grief processes re activated mindfulness sessions however mindfulness found support resolution grief processes encourage adaptive approachbased coping acceptance health neurological impairment injury,0.0
state trait finger tapping performance multiple sclerosis sci rep 2021 aug 24 11 1 17095 doi 101038 s41598021964853abstractfinger tapping tests shown feasible assess motor performance multiple sclerosis ms observed strongly associated estimated clinical severity disease therefore tapping tests adequate tool assess disease status ms study examined potential influencing factors maximum tapping task whole upperlimb 10 s 40 ms patients using linear mixed effects modelling patients tested three sessions two trials per bodyside per session course 427 days inpatient rehabilitation tested factors expanded disability scale edss score laterality ms age sex hand dominance time day session trial first second time sessions reported day form second model used factors examine selfreported day form patients linear mixed effects modelling indicated tapping test good intertrial proportional variance 001 intersession reliability nonsignificant controlling time sessions influence handdominance proportional variance 008 strongly associated edss eta2 022 interaction laterality ms eta2 012 associated reported day form model explained 87 p 001 variance tapping performance lastly able observe positive effect neurologic inpatient rehabilitation task performance obvious significant effect time sessions eta2 0007 longer time spans sessions associated higher increments performance day form impacted edss time day p 001 r2 057 eta2time 0017 eta2edss 0119 conclude tapping test reliable valid assessment tool mspmid34429445 doi101038 s41598021964853,0.0
zeb1 promotes pathogenic th1 th17 cell differentiation multiple sclerosis cell rep 2021 aug 24 36 8 109602 doi 101016 jcelrep2021109602abstractinappropriate cd4+ t helper th differentiation can compromise host immunity promote autoimmune disease identify diseaserelevant regulators t cell fate examined mutations modify risk multiple sclerosis ms canonical organspecific autoimmune disease analysis identified role zinc finger eboxbinding homeobox zeb1 deletion zeb1 protects experimental autoimmune encephalitis eae mouse model multiple sclerosis ms mechanistically zeb1 cd4+ t cells required pathogenic th1 th17 differentiation genomic analyses paired human mouse expression data elucidated unexpected role zeb1 jakstat signaling zeb1 inhibits mir1013p represses jak2 expression stat3 stat4 phosphorylation subsequent expression interleukin17 il17 interferon gamma ifn underscoring clinical relevance zeb1 jak2 downregulation decreases pathogenic cytokines expression t cells ms patients moreover food drug administration fda approved jak2 inhibitor effective eae collectively findings identify conserved potentially targetable mechanism regulating diseaserelevant inflammationpmid34433042 doi101016 jcelrep2021109602,0.0
proinflammatory t helper 17 directly harms oligodendrocytes neuroinflammation proc natl acad sci u s 2021 aug 24 118 34 e2025813118 doi 101073 pnas2025813118abstractt helper th 17 cells considered contribute inflammatory mechanisms diseases multiple sclerosis ms however discussion persists regarding true role patients visualized central nervous system cns inflammatory processes models ms live vivo ms brains discovered cnsinfiltrating th17 cells form prolonged stable contact oligodendrocytes strikingly compared th2 cells direct contact th17 worsened experimental demyelination caused damage human oligodendrocyte processes increased cell death importantly found comparison th2 cells human murine th17 cells express higher levels integrin cd29 linked glutamate release pathways note contact human th17 cells oligodendrocytes triggered release glutamate induced cell stress changes biosynthesis cholesterol lipids revealed singlecell rnasequencing analysis finally exposure glutamate decreased myelination whereas blockade cd29 preserved oligodendrocyte processes th17mediated injury data provide evidence direct deleterious attack th17 cells myelin compartment show potential therapeutic opportunities mspmid34417310 doi101073 pnas2025813118,1.0
pregnancy early life study pearl longitudinal study understand gut microbes contribute maintaining health pregnancy early life background early life period represents first step establishing beneficial microbial ecosystem turn affects short longerterm health changes pregnancy influence neonatal microbiome transmission maternal microbes childbirth beyond nutritional programming however indepth exploration longitudinal maternalinfant cohorts sampling multiple body sites complemented clinical nutritional metadata use cuttingedge experimental systems limitedthe pearl study will increase knowledge microbes including viruses phages bacteria fungi archaea change composition functional capacity pregnancy transmission pathways mother infant impact various factors microbial communities across pregnancy early life eg diet microbes interact microbes modulate host processes including links disease onsetmethodspearl longitudinal observational prospective study 250 pregnant women newborns stool blood samples questionnaires routine clinical data collected pregnancy labour birth 24 months post birthmetagenomic sequencing samples will used define microbiome profiles allow genus species strainlevel taxonomic identification corresponding functional analysis subset samples will analysed host immune metabolite molecules identify factors alter host gut environment culturing will used identify new strains healthpromoting bacteria potential pathogens various vitro vivo experiments will probe underlying mechanisms governing microbemicrobe microbehost interactionsdiscussionlongitudinal studies like pearl critical define biomarkers determine mechanisms underlying microbiome profiles health disease develop new diet microbebased therapies tested future studies clinical trialstrial registrationthis study registered clinicaltrialsgov database id nct03916874,0.0
modulation proteoglycan receptor regulates rhoa crmp2 pathways promotes axonal myelination neurosci lett 2021 jun 21136079 doi 101016 jneulet2021136079 online ahead printabstractthe function myelinating system important defective myelin sheath results various nervous disorders including multiple sclerosis peripheral neuropathies dorsal root entry zone drez transitional area central nervous system cns peripheral nervous system pns generated two types cellsoligodendrocytes schwann cells scs well known injury extracellular matrix including cspg impairs axonal myelination activating protein tyrosine phosphatase ptp cells intracellular sigma peptide isp memetic ptp wedge region competitively binds ptp regulates downstream signaling rhoa present study aimed investigate whether isp increased myelination vivo vitro vitro assay meant verify vivo mechanisms observed isp administration increase axonal myelination vivo vitro furthermore provide evidence oligodendrocytes schwann cells myelinationinduced effects isp application entail inverse expression rhoa crmp2 signaling pathway overall results indicate isp modulation ptp enhances axonal myelination via rhoa crmp2 signaling pathwayspmid34166723 doi101016 jneulet2021136079,1.0
longitudinal network changes conversion cognitive impairment multiple sclerosis neurology 2021 jun 7101212 wnl0000000000012341 doi 101212 wnl0000000000012341 online ahead printabstractobjective characterize functional network changes related conversion cognitive impairment large sample ms patients period 5 yearsmethods 227 ms patients 59 healthy controls hcs amsterdam ms cohort underwent neuropsychological testing restingstate fmri two time points timeinterval 4909 years baseline followup patients categorized cognitively preserved cp n123 mildly impaired mci z15 2 cognitive tests n32 impaired ci z2 2 tests n72 longitudinal conversion groups determined network function quantified using eigenvector centrality measure regional network importance computed individual restingstate networks timepointsresults time 189 patients converted worse phenotype 22 123 cp patients 179 converted cp mci 10 123 cp ci 81 12 32 mci patients converted ci 375 baseline dmn centrality higher ci compared controls p05 longitudinally ventral attention network van importance increased cp driven stable cp cptomci converters p05 conclusions patients 19 worsened cognitive status five years conversion intact cognition impairment related initial disturbed functioning van shifting towards dmn dysfunction ci van normally relays information dmn results indicate ms normal processes crucial maintaining overall network stability progressively disrupted patients clinically progresspmid34099528 doi101212 wnl0000000000012341,0.0
dimethyl fumarate treatment patients primary progressive multiple sclerosis randomized controlled trial neurol neuroimmunol neuroinflamm 2021 aug 24 8 5 e1037 doi 101212 nxi0000000000001037 print 2021 sepabstractbackground objective study whether dimethyl fumarate superior placebo decreasing csf concentrations neurofilament light chain nfl patients primary progressive ms ppms methods doubleblind placebocontrolled phase 2 study dimethyl fumarate treatment progressive multiple sclerosis fumapms patients ppms randomly assigned treatment 240 mg dimethyl fumarate placebo 11 ratio 48 weeks primary endpoint change concentration nfl csf secondary endpoints included csf biomarkers clinical mri measures efficacy evaluated full data set multiple imputations account missing data safety assessed full data setresults fiftyfour patients mean age 549 years sd 61 median expanded disability status scale 40 nterquartile range 4060 disease duration 141 sd 94 21 39 female randomized either placebo n 27 dimethyl fumarate n 27 therapy screening csf concentrations adjusted age sex nfl myelin basic protein mbp soluble cd27 chitinase 3like 1 bcell maturation antigen higher group symptomatic controls twentysix patients 96 dimethyl fumarate group 24 patients 89 placebo group completed randomized phase mean change csf concentrations nfl differ groups mean difference 99 ng l 95 ci 292 491 ng l mbp csf decreased treatment group 182 ng l 95 ci 323 41 ng l compared placebo difference observed multiple imputation data set significant per protocol analysis nominally significant multiple imputation data set per protocol analysis found per protocol analysis secondary tertiary outcomes affected various infections lymphopenia flushing gastrointestinal side effects frequent dimethyl fumarate group serious adverse events similar groupsdiscussion dimethyl fumarate treatment 48 weeks effect investigated efficacy measures patients ppms observe adverse events anticipated dimethyl fumarate treatmenttrial registration information clinicaltrialsgov identifier nct02959658classification evidence study provides class evidence patients ppms dimethyl fumarate treatment effect csf nfl levels compared placebo treatmentpmid34429340 doi101212 nxi0000000000001037,1.0
role hemoglobin subunit delta immunopathy multiple sclerosis mitochondria matters front immunol 2021 aug 24 12709173 doi 103389 fimmu2021709173 ecollection 2021abstractbackground although exact pathophysiology ms identified mitochondrial stress can one culprits ms development herein applied microarray analysis singlecell sequencing analysis ex vivo study elucidate role mitochondrial stress pbmcs ms patientsmethods purpose analyzed gse21942 gse138266 datasets identify degs hub genes pbmcs ms patients describe expression shared genes different immune cells go pathway analysis degs turquoise module genes conducted shed light biological significance validate obtained results gene expression hbd remarkable deg pbmcs affected patients measured pbmcs healthy donors treatmentnave ms patients ms patients treated ga fingolimod dmf ifn1results based wgcna degs analysis hbd hbm slc4a1 lilra5 slc25a37 selenbp1 alyref snrnp40 hint3 identified common genes pmbcs using singlecell sequencing analysis pbmcs characterized various cell populations ms illustrated common gene expression different immune cells furthermore go pathway analysis degs turquoise module genes indicated genes involved immune responses myeloid cell activation leukocyte activation oxygen carrier activity replication fork processing bicarbonate transport pathways ex vivo investigation shown hbd expression treatmentnave rrms patients significantly increased compared healthy donors interest immunomodulatory therapies fingolimod dmf ifn1 significantly decreased hbd expressionconclusion hbd one remarkably upregulated genes pbmcs ms patients hbd substantially upregulated treatmentnave ms patients immunomodulatory therapies fingolimod dmf ifn1 can remarkably downregulate hbd expression based currently available evidence cytoprotective nature hbd oxidative stress can underlying reason hbd upregulation ms nevertheless investigations needed shed light molecular mechanisms hbd oxidative stress ms patientspmid34504491 pmcpmc8421544 doi103389 fimmu2021709173,0.0
covid19 patients neuromyelitis optica spectrum disorders myelin oligodendrocyte glycoprotein antibody disease north america covims registry neurol neuroimmunol neuroinflamm 2021 aug 24 8 5 e1057 doi 101212 nxi0000000000001057 print 2021 sepabstractbackground objective describe impact coronavirus disease 2019 covid19 people neuromyelitis optica spectrum disorders nmosd myelin oligodendrocyte glycoprotein antibody disease mogad methods covid19 infections multiple sclerosis ms related diseases covims registry collected data north american patients ms related diseases laboratorypositive highly suspected sarscov2 infection deidentified data entered webbased registry health care providers data analyzed using ttests pearson 2 tests fisher exact tests categorical variables univariate logistic regression models examined effects risk factors covid19 clinical severityresults june 7 2021 77 patients nmosd 20 patients mogad reported covims registry patients nmosd laboratory positive sarscov2 taking rituximab time covid19 diagnosis patients nmosd hospitalized 649 95 ci 532755 whereas 156 95 ci 83256 hospitalized 91 95 ci 37178 admitted icu ventilated 104 95 ci 46195 died patients nmosd comorbidity sole factor identified poorer covid19 outcome 60 95 ci 1791998 patients mogad laboratory positive sarscov2 almost half taking rituximab among patients mogad 750 hospitalized deaths recorded factors different hospitalized hospitalized admitted icu ventilateddiscussion among reported patients nmosd high mortality rate observed presence comorbid conditions associated worse covid19 outcome deaths reported patients mogad although observations limited due small sample sizepmid34429342 doi101212 nxi0000000000001057,1.0
experimental animal models diabetes related complicationsa review abstractdiabetes mellitus common multifaceted metabolic disorder considered one fastest growing public health problems world characterized hyperglycemia condition high glucose level blood plasma resulting defects insulin secretion action cases impairment secretion also action insulin coexist historically animal models played critical role exploring describing malady pathophysiology recognizable proof targets surveying new remedial specialists vivo medicines present study reviewed experimental models employed diabetes related complications paper reviews briefly broad chemical induction alloxan streptozotocin mechanisms associated type 1 type 2 diabetes also highlighted different models species animals,0.0
st2191 anellated bismorpholino derivative oxyfingolimod shows selective s1p1 agonist functional antagonist potency vitro vivo molecules 2021 aug 24 26 17 5134 doi 103390 molecules26175134abstractsphingosine 1phosphate s1p extensively studied signaling molecule contributes cell proliferation survival migration functions binding specific s1p receptors cycle s1p1 internalization upon s1p binding recycling cell surface local s1p concentrations low drives t cell trafficking s1p1 modulators fingolimod disrupt recycling inducing persistent s1p1 internalization receptor degradation results blocked egress t cells secondary lymphoid tissues approval compounds treatment multiple sclerosis placed development s1pr modulators focus pharmacological research mostly autoimmune indications report novel anellated bismorpholino derivative oxyfingolimod named st2191 exerts selective s1p1 agonist functional antagonist potency st2191 also effective reducing lymphocyte number mice effect dependent phosphorylation sphingosine kinase 2 activity data show st2191 novel s1p1 modulator experiments needed analyze therapeutic impact st2191 animal models autoimmune diseasespmid34500564 doi103390 molecules26175134,0.0
builtin pd1 blocker rescue nk92 activity pdl1mediated tumor escape mechanisms abstractsuccess adoptive cell therapy mainly depends ability immune cells persist function optimally immunosuppressive tumor microenvironment although present cancer site immune cells become exhausted inhibited due presence inhibitory receptors pdl1 malignant cells novel genetic strategies manipulate pd1 pdl1 axis comprise pd1 reversion receptor intracellular domain replaced activating unit ii use antipdl1 car iii disruption pd1 gene present alternative strategy equip therapeutic cells truncated pd1 tpd1 abrogate pd1 pdl1 inhibition show engagement tpd1 pdl1positive tumor unleashes nk92 activity vitro furthermore binding sufficiently strong induce killing targets otherwise recognized nk92 thus increasing range targets vivo treatment nk92 tpd1 cells led reduced tumor growth improved survival importantly tpd1 interfere tumor recognition pdl1 negative conditions thus tpd1 represents straightforward method improving antitumor immunity revealing new targets pdl1 positivity,0.0
norepinephrine modulates il1induced catabolic response human chondrocytes background influence sympathetic nervous system sns metabolism bone cartilage expressing adrenergic receptors ar suggested investigated whether sns functions modulator cartilage metabolism induced interleukin1beta il1 methodshuman articular chondrocytes articular cartilage collected patients osteoarthritis oa chondrocyte monolayer cartilage explant culture stimulated il1 activity ars modulated agonist norepinephrine ne antagonists including propranolol atenolol nebivolol nadololresultsthe levels 1 2 3ar oa cartilage il1treated chondrocytes lower normal cartilage untreated cells treatment chondrocytes il1 blockers including propranolol atenolol nebivolol nadolol 6 h significantly upregulated il1induced expression mmp1 3 13 compared chondrocytes treated il1 alone indicating antagonism ar confers catabolic signals hand ne antagonized il1induced catabolic response addition ne significantly inhibited il1induced release glycosaminoglycan gag cartilage explant culture addition ar activity significantly affected il1stimulated phosphorylation jnk erk results indicate ar signal associated cartilage metabolismconclusionsour findings showed ars regulator cartilage catabolism induced il1,0.0
inhibition p2x4r attenuates white matter injury mice intracerebral hemorrhage regulating microglial phenotypes background white matter injury wmi major neuropathological event associated intracerebral hemorrhage ich p2x purinoreceptor 4 p2x4r member p2x purine receptor family plays crucial role regulating wmi neuroinflammation central nervous system cns diseases study investigated role p2x4r wmi inflammatory response mice well possible mechanism action ichmethodsich induced mice via collagenase injection mice treated 5bdbd ana12 inhibit p2x4r tropomyosinrelated kinase receptor b trkb respectively immunostaining quantitative polymerase chain reaction qpcr performed detect microglial phenotypes inhibition p2x4r western blots wb immunostaining used examine wmi underlying molecular mechanisms cylinder corner turn wire hanging forelimb placement tests conducted evaluate neurobehavioral functionresultsafter ich protein levels p2x4r upregulated especially day 7 ich mainly located microglia inhibition p2x4r via 5bdbd promoted neurofunctional recovery ich well transformation proinflammatory microglia induced ich antiinflammatory phenotype attenuated ichinduced wmi furthermore found trkb blockage can reverse protective effects wmi well neuroprotection 5bdbd treatment result indicates p2x4r plays crucial role regulating wmi neuroinflammation p2x4r inhibition may benefit patients ichconclusionsour results demonstrated p2x4r contributes wmi polarizing microglia proinflammatory phenotype ich furthermore inhibition p2x4r promoted proinflammatory microglia polarization antiinflammatory phenotype enhanced brainderived neurotrophic factor bdnf production bdnf trkb pathway attenuated wmi improved neurological function therefore regulation p2x4r activation may beneficial reducing ichinduced brain injury,1.0
longterm efficacy outcomes natalizumab vs fingolimod patients highly active relapsingremitting multiple sclerosis realworld data multiple sclerosis reference center front neurol 2021 aug 23 12699844 doi 103389 fneur2021699844 ecollection 2021abstractbackground natalizumab ntz fingolimod fty secondline disease modifying treatments dmts approved relapsing remitting multiple sclerosis rrms studies available direct comparison ntz fty based postmarketing experience conflicting results reporting relatively short followup period aim hereby report realworld experience ms center respect ntz vs fty comparison terms efficacy safety referencing longterm followup methods used retrospective data patients received 2ndline treatment ntz since may 2007 fty since september 2011 primary endpoints among others annual edss score mean change baseline time disability worsening improvement annualized relapse rate arr 12 24 months upon total treatment duration time first relapse time radiological progression results total 138 unmatched patients 84 treated ntz 54 treated fty included following propensity score ps matching 31 patients group retained mean followup period ntz ftytreated patients 443 029 359 032 years p 0057 respectively matched analysis time disability improvement time disability worsening comparable groups higher proportion patients remained free relapse ntz compared fty log rank test p 0021 hr 025 95 ci 00808 well free mri activity log rank test p 0006 hr 026 95 ci 00806 treatment discontinuation due mri activity significantly higher ftytreated patients compared ntz log rank test p 0019 hr 012 95 ci 005076 conclusion results indicate toward ntz superiority respect relapse mri activity outcomes fact ntztreated patients may achieve longstanding clinical radiological remission points toward need long followup datapmid34497577 pmcpmc8419322 doi103389 fneur2021699844,0.0
periorbital nociception progressive multiple sclerosis mouse model dependent trpa1 channel activation pharmaceuticals basel 2021 aug 23 14 8 831 doi 103390 ph14080831abstractheadaches frequently described progressive multiple sclerosis pms patients mechanism remains unknown transient receptor potential ankyrin 1 trpa1 involved neuropathic nociception model pms induced experimental autoimmune encephalomyelitis pmseae trpa1 activation causes periorbital facial nociception thus purpose observe development periorbital mechanical allodynia pma pmseae model evaluate role trpa1 periorbital nociception female pmseae mice elicited pma day 7 14 days induction antimigraine agents olcegepant sumatriptan able reduce pma pma diminished trpa1 antagonists hc030031 a967079 metamizole propyphenazone absent trpa1deficient mice enhanced levels trpa1 endogenous agonists nadph oxidase activity detected trigeminal ganglion pmseae mice administration antioxidants apocynin nadph oxidase inhibitor alphalipoic acid sequestrant reactive oxygen species resulted pma reduction results suggest generation trpa1 endogenous agonists pmseae mouse model may sensitise trpa1 trigeminal nociceptors elicit pma thus ion channel potential therapeutic target treatment headache pms patientspmid34451927 doi103390 ph14080831,0.0
fiveyear visual outcomes optic neuritis antimog antibodyassociated disease abstractintroductionoptic neuritis major phenotype clinical attack related demyelinating neurological diseases central nervous system including multiple sclerosis ms antiaquaporin4 aqp4 antibodypositive neuromyelitis optica spectrum disorder nmosd antimyelin oligodendrocyte glycoprotein antibodyassociated disease mogad concept mogad relatively new longterm visual outcomes mogad remains unclearmethodsto elucidate longterm visual prognosis mogad patients mogad whose visual acuity regularly followed 5 years onset enrolled bestcorrected visual acuity bcva nadir acute phase 1 5 years onset evaluated data patients mogad compared patients ms antiaqp4positive nmosdresultstwentythree patients 31 oninvolved eyes mogad 20 patients 24 oninvolved eyes ms 22 patients 24 oninvolved eyes antiaqp4positive nmosd evaluated bcva nadir 1 year 5 years onset much worse antiaqp4positive nmosd ms p00024 mogad p00014 patients mogad antiaqp4positive nmosd serum diseasespecific antibody titer associated subsequent visual prognosis visual acuity almost fully recovered spontaneously shortly initiating acute treatment 22 23 patients mogadon administration highdose intravenous steroid therapy facilitated early recovery visual acuity meanwhile small fraction patients extensive optic nerve lesions involving chiasma irreversibly experienced severe visual impairment despite appropriate acute treatmentconclusionalthough small fraction patients mogad presented extensive optic nerve lesions experienced irreversible severe visual impairment longterm visual outcomes 5 years patients mogad generally good patients ms much better patients antiaqp4positive nmosd,1.0
comprehensive analysis key genes signaling pathways mirnas human knee osteoarthritis based bioinformatics front pharmacol 2021 aug 23 12730587 doi 103389 fphar2021730587 ecollection 2021abstractbackground osteoarthritis oa one main causes disability elderly population accompanied series underlying pathologic changes cartilage degradation synovitis subchondral bone sclerosis meniscus injury present study aimed identify key genes signaling pathways mirnas knee oa associated entire joint components explain potential mechanisms using computational analysis methods differentially expressed genes degs cartilage synovium subchondral bone meniscus identified using gene expression omnibus 2r geo2r analysis based dataset gse43923 gse12021 gse98918 gse51588 respectively visualized volcano plot venn diagram analyses performed identify overlapping degs overlapping degs expressed least two types tissues mentioned gene ontology go enrichment analysis kyoto encyclopedia genes genomes kegg analysis proteinprotein interaction ppi analysis module analysis conducted furthermore qrtpcr performed validate results using clinical specimens results result total 236 overlapping degs identified 160 upregulated 76 downregulated enrichment analysis constructing ppi network mirnamrna network knee oarelated key genes hey1 ahr vegfa myc cxcl12 identified clinical validation qrtpcr experiments supported computational results addition knee oarelated key mirnas mir101 mir181a mir29 mir9 mir221 pathways wnt signaling hif1 signaling pi3kakt signaling axon guidance pathways also identified among identified knee oarelated key genes pathways mirnas genes ahr hey1 myc gap43 ptn pathways like axon guidance mirnas mir17 mir21 mir155 mir185 mir1 lack research worthy future investigation conclusion present informatic study first time provides insight potential therapeutic targets knee oa comprehensively analyzing overlapping genes differentially expressed multiple joint components relevant signaling pathways interactive mirnaspmid34497524 pmcpmc8419250 doi103389 fphar2021730587,0.0
sexspecific signatures intrinsic hippocampal networks regional integrity underlying cognitive status multiple sclerosis brain commun 2021 aug 23 3 3 fcab198 doi 101093 braincomms fcab198 ecollection 2021abstractthe hippocampus anatomically compartmentalized structure embedded highly wired networks essential cognitive functions hippocampal vulnerability postulated acute chronic neuroinflammation multiple sclerosis patterns occurring inflammation neurodegeneration compensation yet described besides focal damage hippocampal tissue network disruption important contributor cognitive decline multiple sclerosis patients postulate sexspecific trajectories hippocampal network reorganization regional integrity address relationship markers neuroinflammation cognitive memory performance clinical severity large cohort multiple sclerosis patients n 476 337 females age 35 10 years disease duration 16 14 months healthy subjects n 110 54 females age 34 15 years utilized mri baseline 2year followup quantify regional hippocampal volumetry reconstruct singlesubject hippocampal networks graph analytical tools assessed clustered topology hippocampal networks mixedeffects analyses served model sexbased differences hippocampal network subfield integrity multiple sclerosis patients healthy subjects time points longitudinally afterwards hippocampal network subfield integrity related clinical radiological variables dependency sex attribution found clustered network architecture female male patients compared healthy counterparts time points female patients displayed clustered network topology comparison male patients time multiple sclerosis patients developed even clustered network architecture though greater magnitude females detected reduced regional volumes addressed hippocampal subfields female male patients compared healthy subjects compared male patients females displayed lower volumes para presubiculum higher volumes molecular layer longitudinally volumetric alterations pronounced female patients showed extensive regional tissue loss despite comparable cognitive memory performance female male patients followup period identified strong interrelation hippocampal network properties cognitive memory performance female patients findings evidence clustered hippocampal network topology female patients extensive subfield volume loss time stronger relation cognitive memory performance network topology female patients suggests greater entrainment brains reserve results may serve adapt sextargeted neuropsychological interventionspmid34514402 pmcpmc8417841 doi101093 braincomms fcab198,0.0
agerelated alteration characteristics function transcription features adscs background objectivesadipose tissuederived stem cells adscs autologous transplantation promising strategy agingrelated disorders however relationship adscs senescence organismal aging clearly established therefore aimed evaluating senescence properties adscs different age donors verify influence organismal aging proliferation function adscs vitro providing theoretical basis clinical application autologous adscs transplantationmethods resultsthe adscs obtained 1monthold 20monthold mice cells characteristics functions gene expression levels apoptosis proportion cell cycle sagal staining transcription features evaluated compared adscs 1monthold mice adscs 20monthold mice exhibited senescenceassociated changes including inhibited abilities proliferate moreover differentiation abilities cell surface markers cytokines secreting differed 1m 20m adscs sagal staining reveal differences two donor groups cells exhibited remarkable agerelated changes continuous passages based transcriptome analysis detection ccl7ccl2ccr2 axis probable mechanism differencesconclusionsadscs old donors agerelated alterations ccl7ccl2ccr2 axis potential target gene therapy reduce harmful effects adscs old donors improve autologous transplantation recommend adscs cryopreserved youth minimum number passages block ccl7ccl2ccr2 abolish effects agerelated alterations adscs chemokine signaling pathway,0.0
potential pathogenic role interleukin6 child ancanegative pauciimmune crescentic glomerulonephritis case report literature review background crescentic glomerulonephritis disease characterized severe glomerular injuries classified five different pathological types patients type v disease pauciimmune crescentic glomerulonephritis picgn negative antineutrophil cytoplasmic autoantibodies ancas limited clinical data manifestations treatment prognosis type v crescentic glomerulonephritis especially childrencase presentationa 13yearold girl intermittent fever 10 months admitted hospital gross hematuria oliguria edema hypertension tests indicated decreased glomerular filtration rate hematuria proteinuria elevated level il6 antinuclear antibody spectrum test positive 11000 anca antiglomerular basement membrane antibody tests negative renal biopsy confirmed diagnosis ancanegative picgn administered methylprednisolone pulse therapy intravenous cyclophosphamide oral mycophenolate mofetil 3month followup urine protein level significantly lower serum creatinine level normal rangeconclusionsfever may extrarenal manifestation ancanegative picgn il6 may play role pathogenesis disease early methylprednisolone pulse therapy immunosuppressant may reduce symptoms improve prognosis,0.0
walking uango exoskeleton training compliance multiple sclerosis patient neurol int 2021 aug 23 13 3 428438 doi 103390 neurolint13030042abstractbackground multiple sclerosis progressive neurodegenerative disease affects myelin central nervous system complex unpredictable occurs predominantly young adults causing increasing disability significantly lower quality life recent studies investigated rehabilitation training use robotic exoskeleton can influence walking recovery patients serious neurological diseaseaim purpose study analyze first approach multiple sclerosis patient robotic exoskeleton lower limbs order assess effectiveness protocol walking ability adaptability device level appreciation variations parameters related walking fatigue perceptionmethods study conducted 71yearold male diagnosed primary progressive multiple sclerosis since 2012 edss score 6 patient underwent cycle 10 sessions treatment exoskeleton lower limbs uango lasting 1 h 30 min pre posttreatment evaluations carried 6 min walking test fatigue severity scale short form36 health survey likert scale review session blood pressure heart rate peripheral saturation monitored addition perception fatigue borg scale studiedresult comparison initial final evaluations showed improvements walked distance 6 mwt t0 53 m t1 61 m positive trend saturation heart rate values collected session improvements found borg scale t0 15 t1 11 discussion data collected case report show promising results regarding treatment multiple sclerosis patients uango exoskeleton benefits motor performance vital parameterspmid34449717 doi103390 neurolint13030042,1.0
targeting autonomic flexibility enhance cognitive training outcomes older adults mild cognitive impairment study protocol randomized controlled trial abstractimportancecognitive training components can enhance transferred longterm effects slow progress dementia needed preventing dementiaobjectivethe goal study test whether improving autonomic nervous system ans flexibility via resonance frequency breathing rfb training will strengthen effects visual speed processing vsop cognitive training cognitive brain function slow progress dementia older adults mild cognitive impairment mci designstage ii doubleblinded randomized controlled trial study prospectively registered clinicaltrialsgov registration approved 21 august 2020 nct04522791 settingstudyrelated appointments will conducted onsite university rochester medical center locations data collection will conducted august 2020 february 2025participantsolder adults mci n 114 will randomly assigned 8week combined intervention rfb+vsop vsop guided imagery relaxation ir control ironly control periodical booster training sessions followups mechanistic distal outcomes include ans flexibility measured heart rate variability multiple markers dementia progress data will collected across 14month perioddiscussionthis will among first rcts examine older persons mci novel combined intervention targeting ans flexibility important contributor overall environmental adaptation ultimate goal slowing neurodegenerationtrial registrationclinicaltrialsgov nct04522791 registered 21 august 2020protocol version study00004727 irb protocol version 2 approved 30 july 2020,0.0
importance extracellular vesicle secretion bloodcerebrospinal fluid interface pathogenesis alzheimers disease abstractincreasing evidence indicates extracellular vesicles evs play important role pathogenesis alzheimers disease ad previously reported bloodcerebrospinal fluid csf interface formed choroid plexus epithelial cpe cells releases increased amount evs csf response peripheral inflammation studied importance cpmediated ev release ad pathogenesis observed increased ev levels csf young transgenic app ps1 mice correlated high amyloid beta csf levels age intracerebroventricular icv injection oligomers ao wildtype mice revealed significant increase evs csf signifying presence csfao sufficient induce increased ev secretion using vivo vitro ex vivo approaches identified cp major source csfevs interestingly aoinduced cpderived evs induced proinflammatory effects mixed cortical cultures proteome analysis evs revealed presence several proinflammatory proteins including complement protein c3 strikingly inhibition ev production using gw4869 resulted protection acute aoinduced cognitive decline research underlying mechanisms ev secretion might open novel therapeutic strategies impact pathogenesis progression ad,0.0
clinical characteristics middleaged older patients ms treated interferon beta1b posthoc analysis 2year prospective international observational study background despite trends towards increased age patients living multiple sclerosis ms little known response older adults ms diseasemodifying therapies dmts thus posthoc analysis undertaken using data 2year international noninterventional prospective cohort study nct00787657 beacon betaferon prospective study adherence coping nurse support patients age 40 years ms starting interferon beta1b ifnb1b treatment within 6 months study entrymethodsmiddleaged older patients ms divided two subgroups 4150 years 50 years treatment ifnb1b started within 6 months study entry patients followedup 2year observation period assessments included disease history course annualised relapse rate arr expanded disability scale score edss treatment adherence hospital anxiety depression scale hads adverse events ae resultsat baseline intentiontotreat itt population n 481 aged 4150 years n 327 50 years n 154 mean standard deviation sd ages 451 28 562 42 years maximum age 72 years duration ms since onset symptoms 39 52 59 71 years respectively baseline proportion patients relapsingremitting ms rrms 963 949 secondary progressive ms spms 37 51 4150 50 years subgroups respectively arr 2 years study start 093 048 086 054 4150 50 years groups respectively decreased since study start 020 109 007 037 respectively percentage patients anxiety depression measured hads stable study period polypharmacy five medications seen 323 412 patients aged 4150 50 years unexpected aes reportedconclusionsthis study provides observational data patients 40 72 years age suggesting ifnb1b can effective welltolerated treatment option ms patients advanced agetrial registrationclinicaltrialsgov nct00787657,0.0
treatment approaches patients multiple sclerosis coexisting autoimmune disorders ther adv neurol disord 2021 aug 23 1417562864211035542 doi 101177 17562864211035542 ecollection 2021abstractthe past decades yielded major therapeutic advances many autoimmune conditions multiple sclerosis ms thus ushered new era targeted increasingly potent immunotherapies yet growing arsenal therapeutic immune interventions also rendered therapy much challenging attending physician especially treating patients one autoimmune condition importantly therapeutic strategies either approved several autoimmune disorders may repurposed conditions therefore opening new curative possibilities related fields article especially focus frequent therapeutically relevant concomitant autoimmune conditions faced neurologists treating patients ms namely psoriasis rheumatoid arthritis inflammatory bowel diseases provide overview available diseasemodifying therapies highlight possible contraindications show pathophysiological overlaps finally present therapeutics can utilized combinatory treatment order kill two birds one stonepmid34457039 pmcpmc8388232 doi101177 17562864211035542,0.0
contribution tissue inflammation bloodbrain barrier disruption brain softening mouse model multiple sclerosis front neurosci 2021 aug 23 15701308 doi 103389 fnins2021701308 ecollection 2021abstractneuroinflammatory processes occurring multiple sclerosis cause disseminated softening brain tissue quantified vivo magnetic resonance elastography mre however inflammationmediated tissue alterations underlying mechanical integrity brain remain unclear previously showed bloodbrain barrier bbb disruption visualized mri using gadoliniumbased contrast agent gbca correlate tissue softening active experimental autoimmune encephalomyelitis eae however unknown confined bbb changes inflammatory processes may determine local elasticity changes therefore aim elucidate inflammatory hallmarks determinant local viscoelastic changes observed eae brains hence novel multifrequency mre applied combination gbcabased mri small superparamagnetic iron oxide particles vsops female sjl mice induced adoptive transfer eae n 21 vsops doped europium euvsops facilitate postmortem analysis accumulation euvsops previously demonstrated sensitive immune cell infiltration ecm remodeling also found independent gbca enhancement following registration reference brain atlas viscoelastic properties whole brain areas visualized either gd vsop quantified mre revealed marked disseminated softening across whole brain mice established eae baseline 31 01 m s vs eae 29 02 m s p 00001 similar degree softening observed sites gbca enhancement ie mainly within cerebral cortex brain stem baseline 33 04 m s vs eae 30 05 m s p 0018 however locations euvsop accumulated mainly fiber tracts baseline 30 04 m s vs eae 26 05 m s p 0023 softening pronounced compared nonhypointense areas percent change stiffness euvsop accumulation 1681 1649 vs nonhypointense regions 585 381 p 0048 findings suggest multifrequency mre sensitive differentiate local inflammatory processes strong immune cell infiltrate lead vsop accumulation disseminated inflammation bbb leakage visualized gbca pathological events visualized euvsop mri mre may include gliosis macrophage infiltration alterations endothelial matrix components extracellular matrix remodeling mre may therefore represent promising imaging tool noninvasive clinical assessment different pathological aspects neuroinflammationpmid34497486 pmcpmc8419310 doi103389 fnins2021701308,0.0
identification characterisation cisregulatory elements upstream human receptor tyrosine kinase gene mertk brain plast 2021 aug 23 7 1 316 doi 103233 bpl200102 ecollection 2021abstractbackground mertk encodes receptor tyrosine kinase regulates immune homeostasis via phagocytosis apoptotic cells cytokinemediated immunosuppression mertk highly expressed central nervous system cns specifically myeloid derived innate immune cells dysregulation implicated cns pathologies including autoimmune disease multiple sclerosis ms objective cell types tissues express mertk well described genetic elements define genes promoter regulate specific transcription domains remain unknown primary objective study define characterise human mertk promoter regionmethods cloned characterized 5 upstream region mertk identify cisacting dna elements promote gene transcription luciferase reporter assays addition promoter regions tested sensitivity antiinflammatory glucocorticoid dexamethasoneresults study identified identified proximal distalacting dna elements promote transcription strongest promoter activity identified 850 bp region situated 3 kb upstream mertk transcription start site serial deletions putative enhancer revealed entire region essential expression activity using silico analysis identified several candidate transcription factor binding sites despite wellestablished upregulation mertk response antiinflammatory glucocorticoids dna region within 5 kb putative promoter found directly respond dexamethasone treatmentconclusions elucidating genetic mechanisms regulate mertk expression gives insights gene regulation homeostasis disease providing potential targets therapeutic modulation mertk transcriptionpmid34631417 pmcpmc8461731 doi103233 bpl200102,0.0
vivo evidence functional disconnection brainstem monoaminergic nuclei brain networks multiple sclerosis abstractbackground brainstem monoaminergic dopaminergic noradrenergic serotoninergic nuclei brmn contain variety ascending neurons diffusely project whole brain crucially regulating normal brain function brmn directly affected multiple sclerosis ms inflammation neurodegeneration moreover inflammation reduces synthesis monoamines aberrant monoaminergic neurotransmission contributes pathogenesis ms explains clinical features ms used restingstate functional mri rsfmri characterize abnormal patterns brmn functional connectivity fc msmethods brmn fc studied multiecho rsfmri n68 relapsingremitting ms patients n39 healthy controls hc performing seedbased analysis producing standard space seed masks brmn fc assessed ventral tegmental area vta locus coeruleus lc median raphe mr dorsal raphe dr rest brain compared ms patients hc betweengroup comparisons carried within main effect observed hc setting p005 familywiseerror corrected fwe results hc vta displayed fc core regions defaultmode network compared hc ms patients showed altered fc vta posterior cingulate cortex p005fwe lc displayed fc core regions executivecontrol network reduced functional connection lc right prefrontal cortex ms patients p005fwe raphe nuclei functionally connected cerebellar cortex significantly lower fc nuclei cerebellum ms patients compared hc p005fwe conclusions study demonstrated ms patients functional disconnection brmn cortical subcortical efferent targets central brain networks possibly due loss dysregulation brmn neurons adds new information monoaminergic systems contribute ms pathogenesis suggests new potential therapeutic targets,0.0
relapsing neuromyelitis optica adolescent girl bmj case rep 2021 aug 23 14 8 e242402 doi 101136 bcr2021242402abstractearly differentiation neuromyelitis optica spectrum disorder nmosd multiple sclerosis ms paramount importance nmosd especially relapsing variant severe morbidity ms describe case adolescent girl presented repeated episodes optic neuritis period 4 years normal brain mri scans treated initially relapsing remitting ms showing clinical evidence transverse myelitis tm eventually diagnosed nmosd pulse intravenous methyl prednisolone along immunosuppressive therapy led remission disease however delay diagnosis nmosd led visual disability left eye therefore young patients recurrent optic neuritis normal brain mri may prudent get spinal mri done look tm even asymptomatic addition keep low threshold requesting aquaporin4 antibody testing patientspmid34426420 doi101136 bcr2021242402,0.0
genetically predicted milk intake risk neurodegenerative diseases nutrients 2021 aug 23 13 8 2893 doi 103390 nu13082893abstractmilk intake associated risk neurodegenerative diseases observational studies nevertheless whether association causal remains unknown adopted mendelian randomization design evaluate potential causal association milk intake common neurodegenerative diseases including multiple sclerosis ms alzheimers disease ad amyotrophic lateral sclerosis als parkinsons disease pd genetic associations neurodegenerative diseases obtained international multiple sclerosis genetics consortium n 80 094 finngen consortium n 176 899 ad gwas n 63 926 webbased study parkinsons disease n 308 518 pdgene n 108 990 als gwas n 80 610 lactase persistence variant rs4988235 lct13910 c t used instrumental variable milk intake genetically predicted higher milk intake associated decreased risk ms ad increased risk pd additional milk intake increasing allele odds ratios 094 95 confidence intervals ci 091097 p 151 104 ms 097 094099 p 0019 ad 109 95ci 106112 p 930 109 pd genetically predicted milk intake associated als odds ratio 097 95ci 094101 p 0135 results suggest genetically predicted milk intake associated decreased risk ms ad increased risk pd investigations needed clarify underlying mechanismspmid34445060 doi103390 nu13082893,0.0
vitamin d3 estradiol alter pad2 expression activity levels c6 glioma cells abstractmultiple sclerosis ms known chronic demyelinating disease multifactorial etiology suggested deimination myelin basic proteins mbps peptidyl arginine deiminase 2 pad2 may increase citrulline residues resulting reduction myelin sheath density progression multiple sclerosis aim study investigate effects vitamin d 25hydroxy cholecalciferol d3 estradiol pad2 gene expression level catalytic activity rat c6 glioma cells c6 glioma cells cultured dmem medium treated vitamin d 10 100ng ml estradiol 10 100m based cellular viability pad2 gene expression catalytic activity evaluated using realtime qrtpcr spectrophotometry techniques respectively pad2 gene expression level catalytic activity increased significantly estradioltreated cells p00435 p00015 respectively conversely vitamin d downregulated significantly pad2 gene expression level p0015 activity p0017 study results suggested estradiol conversely vitamin d increases activity pad2 enzyme might develop multiple sclerosis especially women,1.0
update novel approaches diagnosis treatment sarscov2 infection abstractthe ongoing pandemic coronavirus disease 2019 covid19 made serious public health economic crisis worldwide united global efforts develop rapid precise costefficient diagnostics vaccines therapeutics numerous multidisciplinary studies techniques designed investigate develop various approaches help frontline health workers policymakers populations overcome disease techniques reviewed within individual disciplines now timely provide crossdisciplinary overview novel diagnostic therapeutic approaches summarizing complementary efforts across multiple fields research technology accordingly reviewed summarized various advanced novel approaches used diagnosis treatment covid19 help researchers across diverse disciplines prioritization resources research development give better picture latest techniques include artificial intelligence nanobased crisprbased mass spectrometry technologies well neutralizing factors traditional medicines also reviewed new approaches vaccine development developed dashboard provide frequent updates current future approved vaccines,0.0
identifying causal models genetically regulated methylation patterns gene expression healthy colon tissue background dna methylation involved regulation gene expression phenotypic variation interrelationship genetic variation dna methylation gene expression remains poorly understood combine analysis genetic variants related methylation markers methylation quantitative trait loci mqtls gene expression expression quantitative trait loci eqtls methylation markers related gene expression expression quantitative trait methylation eqtms provide novel insights genetic epigenetic architecture colocalizing molecular markersresultsnormal mucosa 100 patients colon cancer 50 healthy donors included colonomics project analyzed linear models used find mqtls eqtms within 1 mb target gene 32 446 eqtls previously detected found total 6850 snps 114 cpgs 52 genes interrelated generating 13 987 significant combinations cooccurring associations meqtls bonferromi correction nonredundant meqtls 54 enriched genes involved metabolism glucose xenobiotics immune system snps meqtls enriched regulatory elements enhancers promoters compared random snps within 1 mb genes three colorectal cancer gwas snps related methylation changes four snps related chemerin levels bayesian networks used identify putative causal relationships among associated snps cpg gene expression triads identified combinations showed canonical pathway methylation markers causes gene expression variation 601 noncausal relationship methylation gene expression 339 however 6 combinations gene expression causing variation methylation markersconclusionsin study provided characterization regulation genetic variants interdependent methylation markers gene expression set 150 healthy colon tissue samples important finding understanding molecular susceptibility colonrelated complex diseases,0.0
antiaqp4 autoantibodies promote atp release astrocytes induce mechanical pain rats background intractable neuropathic pain common symptom neuromyelitis optica spectrum disorder nmosd however underlying mechanism nmosd pain remains elucidated study focused atp one damageassociated molecular patterns also wellrecognized molecule involved peripheral neuropathic painmethodswe assessed development pain symptoms injecting antiaqp4 recombinant autoantibodies raqp4 igg rat spinal cords incubated hek293 cells expressing aqp4 hekaqp4 rat astrocytes raqp4 igg assessed level atp supernatant performed transcriptome analysis spinal cords injected raqp4 igg pharmacological inhibition also applied investigate involvement atp development neuropathic pain rat model atp concentration within cerebrospinal fluid examined patients nmosd neurological diseasesresultsdevelopment mechanical allodynia confirmed raqp4 iggtreated rats aqp4abmediated extracellular atp release astrocytes observed vitro pharmacological inhibition atp receptor reversed mechanical allodynia raqp4 iggtreated rats furthermore transcriptome analysis revealed elevation gene expressions related several atp receptors including p2rx4 il1b spinal cord raqp4 iggtreated rats patients csf atp concentration significantly higher acute remission phase nmosd multiple sclerosis neurological disordersconclusionantiaqp4 antibody shown induce release extracellular atp astrocytes atpmediated development mechanical allodynia also suggested rats treated antiaqp4 antibody study indicates pivotal role atp pain mechanism nmosd,0.0
reducing health effects hot weather heat extremes personal cooling strategies green cities lancet 2021 aug 21 398 10301 709724 doi 101016 s01406736 21 012095abstractheat extremes ie heatwaves already serious impact human health ageing poverty chronic illnesses aggravating factors global community seeks contend even hotter weather future consequence global climate change pressing need better understand effective prevention response measures can implemented particularly lowresource settings series paper describe future reliance air conditioning unsustainable marginalises communities vulnerable heat show holistic understanding thermal environment landscape urban building individual scales supports identification numerous sustainable opportunities keep people cooler summarise benefits eg effectiveness limitations identified cooling strategy recommend optimal interventions settings aged care homes slums workplaces mass gatherings refugee camps playing sport integration information well communicated heat action plans robust surveillance monitoring essential reducing adverse health consequences current future extreme heatpmid34419206 doi101016 s01406736 21 012095,0.0
tetraspanins unevenly distributed across single extracellular vesicles bias sensitivity multiplexed cancer biomarkers background tetraspanin expression extracellular vesicles evs often used surrogate detection classification practice typically assumes consistent expression across ev sourcesresultshere demonstrate distinct patterns colocalization tetraspanin expression evs enriched variety vitro vivo sources report optimized method use single particle antibodycapture fluorescence detection identify subpopulations according tetraspanin expression compare findings nanoscale flow cytometry found tetraspanin profile consistent given ev source regardless isolation method tetraspanin profiles distinct across various sources tetraspanin profiles measured flow cytometry totally agree suggesting limitations subpopulation detection significantly impact apparent protein expression analyzed tetraspanin expression single evs captured nonspecifically revealing tetraspanin capture can bias apparent multiplexed tetraspanin profile finally demonstrate bias can significant impact diagnostic sensitivity tumorassociated ev surface markersconclusionour findings may reveal key insights protein expression heterogeneity evs better inform ev capture detection platforms diagnostic downstream usegraphical abstract,0.0
bacteraemia antimicrobial susceptibility treatment among campylobacterassociated hospitalisations australian capital territory review background campylobacter spp cause mostly selflimiting enterocolitis although significant proportion cases require hospitalisation highlighting potential severe disease among people admitted blood culture specimens frequently collected antibiotic treatment initiated sought understand clinical host factors associated bacteraemia antibiotic treatment isolate nonsusceptibility among campylobacterassociated hospitalisationsmethodsusing linked hospital microbiology administrative data identified reviewed campylobacterassociated hospitalisations 2004 2013 calculated populationlevel incidence campylobacter bacteraemia used logistic regression examine factors associated bacteraemia antibiotic treatment isolate nonsusceptibility among campylobacterassociated hospitalisationsresultsamong 685 campylobacterassociated hospitalisations identified 25 admissions bacteraemia estimated incidence 071 cases per 100 000 population per year around half hospitalisations 333 685 blood culturing performed factors associated bacteraemia included underlying liver disease aor 4889 95 ci 70334022 p 0001 haematology unit admission aor 1467 95 ci 2997207 p 0001 age 7079 years aor 493 95 ci 1571549 approximately onethird 219 685 admissions received antibiotics treatment rates increasing significantly time p 005 factors associated antibiotic treatment included gastroenterology unit admission aor 375 95 ci 195720 p 0001 blood cultures taken aor 276 95 ci 179426 p 0001 age 4049 years aor 234 95 ci 114479 p 002 nonsusceptibility isolates standard antimicrobials increased significantly time p 001 associated overseas travel aor 1180 95 ci 3184383 p 0001 negatively associated tachycardia aor 048 95ci 026088 p 002 suggesting healthy traveller effectconclusionscampylobacter infections result considerable hospital burden among admitted hospital interplay factors involving clinical presentation presence underlying comorbidities complications increasing age influence case investigated managed,0.0
discovery metabolic biomarkers gestational diabetes mellitus chinese population background gestational diabetes mellitus gdm one common pregnancy complications can lead morbidity mortality mother infant metabolomics provided new insights pathology gdm systemic analysis gdm metabolites required providing clues gdm diagnosis mechanism research study aims reveal metabolic differences normal pregnant women gdm patients second thirdtrimester stages confirm clinical relevance new findingsmethodsmetabolites quantitated serum samples 200 healthy pregnant women 200 gdm women second trimester 199 normal controls 199 gdm patients third trimester function pathway analyses applied explore biological roles involved two sets metabolites trimester stagespecific gdm metabolite biomarkers identified combining machine learning approaches logistic regression models constructed evaluate predictive efficiency finally weighted gene coexpression network analysis method used capture associations metabolite modules biomarkers clinical indicesresultsthis study revealed 57 differentially expressed metabolites dems discovered secondtrimester group among significant one 3methyl2oxovaleric acid similarly 72 dems found thirdtrimester group significant metabolites ketoleucine alphaketoisovaleric acid dems mainly involved metabolism pathway amino acids fatty acids bile acids logistic regression models selected metabolite biomarkers achieved area curve values 0807 081 second thirdtrimester groups furthermore significant associations found dems biomarkers gdmrelated indicesconclusionsmetabolic differences healthy pregnant women gdm patients found associations biomarkers clinical indices also investigated may provide insights pathology gdm,0.0
vitamin d thyroid disorders systematic review metaanalysis observational studies background contribution vitamin d thyroid disorders received paramount attention however results mixed hence designed systematic review metaanalysis obtain definitive conclusionmethodsthe search included pubmed isi web science scopus google scholar databases march 2021 collect available papers reporting relationship serum levels vitamin d thyroid disorders pooled effect reported weighted mean difference wmd 95 confidence interval ci resultsout 6123 datasets 42 eligible get systematic review metaanalysis serum vitamin d markedly lower autoimmune thyroid diseases aitd wmd 31 ng dl 95 ci 557 066 p 0013 i2 999 hashimotos thyroiditis ht wmd 605 ng dl 95 ci 835 375 p 0001 i2 910 hypothyroidism patients wmd 1343 ng dl 95 ci 2604 081 p 003 i2 995 subjects graves disease gd wmd 414 ng dl 95 ci 846 017 p 006 i2 975 conclusionsour findings suggested lower vitamin d levels patients hypothyroidism aitd ht compared healthy subjects however link serum vitamin d gd significant among subjects 40 years old,0.0
abnormal expression profile plasmaderived exosomal micrornas patients treatmentresistant depression abstractwhether micrornas mirnas plasma exosomes might dysregulated patients depression especially treatmentresistant depression trd remains unclear based study novel biomarkers therapeutic targets discovered end small sample study performed isolation plasma exosomes patients trd diagnosed hamilton scale study 4 peripheral plasma samples patients trd 4 healthy controls collected extraction plasma exosomes exosomal mirnas analyzed mirna sequencing followed image collection expression difference analysis target gene go enrichment analysis kegg pathway enrichment analysis compared healthy controls 2 mirnas plasma exosomes patients trd showed significant differences expression among hasmir3355p significantly upregulated hasmir12923p significantly downregulated go kegg analysis showed dysregulated mirnas affect postsynaptic density axonogenesis well signaling pathway axon formation cell growths identification mirnas target genes may provide novel biomarkers improving diagnosis accuracy treatment effectiveness trd,0.0
targeting akt cancer precision therapy abstractbiomarkersguided precision therapeutics revolutionized clinical development administration moleculartargeted anticancer agents tailored precision cancer therapy exhibits better response rate compared unselective treatment protein kinases critical roles cell signaling metabolism proliferation survival migration aberrant activation protein kinases critical tumor growth progression hence protein kinases key targets molecular targeted cancer therapy serine threonine kinase akt frequently activated various types cancer activation akt promotes tumor progression drug resistance since first akt inhibitor reported 2000 many akt inhibitors developed evaluated either early late stage clinical trials take advantage liquid biopsy genomic molecular profiling realize personalized cancer therapy two inhibitors capivasertib ipatasertib tested phase iii clinical trials cancer therapy highlight recent progress akt signaling pathway review uptodate data clinical studies akt inhibitors discuss potential biomarkers may help personalized treatment cancer akt inhibitors addition also discuss akt may confer vulnerability cancer cells kinds anticancer agents,0.0
need personal experiences sort documentation qualitative study people multiple sclerosis seek information dietary herbal supplements background use dietary herbal supplements dihes widespread among people multiple sclerosis pwms pwms highly informed patient group use several types sources seek information subjects related disease however still unknown pwms seek information dihes important pwms make decisions dihes based accurate useful accessible information therefore aim study explore pwms seek information dihes experience engage informationmethodssemistructured interviews conducted eighteen pwms using dihes participants selected crosssectional survey diversity sampling used based relevant characteristics gender number dihes used past 12 months interviews conducted facetoface telephone lasted 30 min 1 hour interviews recorded transcribed verbatim analyzed using thematic network analysis nvivo 12 pro softwareresultsthree main themes emerged analysis engaging healthcare professionals hcps regarding dihes ii social networks source information regarding dihes iii reliance bodily sensations participants navigated three types sources participants point discussed dihes hcp information hcps considered reliable valuable hcps viewed uncommitted dialogue dihes recommendations others often driver decisions regarding use dihes however information pwms networks overwhelming difficult navigate finally pwms relied experiences regarding dihes let bodily sensations guide use dihesconclusionsparticipants often rely three types information sources create nuanced comprehensive information base however pwms may feel overwhelmed confused information gathered findings indicate need better guidance pwms concerning dihes openness among hcps engage dialogue,0.0
meeting report fourth annual triservice microbiome consortium symposium abstractthe triservice microbiome consortium tsmc founded enhance collaboration coordination communication microbiome research among us department defense dod organizations annual tsmc symposium designed enable information sharing dod scientists leaders field microbiome science thereby keeping dod consortium members informed latest advances within microbiome community facilitating development new collaborative research opportunities 2020 annual symposium held virtually 2425 september 2020 presentations discussions centered microbiomerelated topics within four broad thematic areas 1 enabling technologies 2 microbiome health performance 3 environmental microbiome 4 microbiome analysis discovery report summarizes presentations outcomes 4th annual tsmc symposium,0.0
mesenchymal stem cellbased therapy exosomes covid19 current trends prospects abstractnovel coronavirus disease 2019 covid19 caused severe acute respiratory syndrome coronavirus2 virus causes exaggerated immune response resulting cytokine storm acute respiratory distress syndrome leading cause covid19related mortality morbidity far therapies succeeded circumventing exacerbated immune response cytokine storm associated covid19 mesenchymal stem cells mscs immunomodulatory regenerative activities mostly mediated paracrine effect extracellular vesicle production therapeutic potential many autoimmune inflammatory degenerative diseases paper review clinical studies use mscs covid19 treatment including salutary effects mscs pathophysiology covid19 immunomodulation cytokine storm ongoing clinical trial designs cell sources dose administration populations summarized paracrine mode benefit discussed also offer suggestions optimizing mscbased therapies including genetic engineering strategies cell surface modification nanotechnology applications combination therapies,1.0
dysphagia reflux related sequelae due altered physiology scleroderma world j gastroenterol 2021 aug 21 27 31 52015218 doi 103748 wjgv27i315201abstractsystemic sclerosis connective tissue disease presents significant gastrointestinal involvement commonly esophagus dysphagia common clinical manifestation systemic sclerosis strongly related esophageal dysmotility however multiple contributing factors step physiology swallowing may contribute development severe dysphagia oral phase swallowing may disrupted poor mastication due microstomia poor dentition well xerostomia pharyngeal phase swallowing pharyngeal muscle weakness due concurrent myositis cricopharyngeal muscle tightening due acid reflux can cause disturbance esophageal phase swallowing commonly disturbed decreased peristalsis esophageal dysmotility however can also affected obstruction chronic reflux changes pillinduced esophagitis candida esophagitis contributing factors dysphagia include difficulties food preparation gastroparesis understanding anatomy physiology swallowing evaluating systemic sclerosis patients presenting dysphagia disturbances step can allow development better treatment plans improve dysphagia overall quality lifepmid34497445 pmcpmc8384755 doi103748 wjgv27i315201,0.0
hot weather heat extremes health risks lancet 2021 aug 21 398 10301 698708 doi 101016 s01406736 21 012083abstracthot ambient conditions associated heat stress can increase mortality morbidity well increase adverse pregnancy outcomes negatively affect mental health high heat stress can also reduce physical work capacity motorcognitive performances consequences productivity increase risk occupational health problems almost half global population 1 billion workers exposed high heat episodes third exposed workers negative health effects however excess deaths many heatrelated health risks preventable appropriate heat action plans involving behavioural strategies biophysical solutions extreme heat events becoming permanent features summer seasons worldwide causing many excess deaths heatrelated morbidity mortality projected increase climate change progresses greater risk associated higher degrees global warming particularly tropical regions increased warming might mean physiological limits related heat tolerance survival will reached regularly often coming decades climate change interacting trends population growth ageing urbanisation socioeconomic development can either exacerbate ameliorate heatrelated hazards urban temperatures enhanced anthropogenic heat vehicular transport heat waste buildings although evidence adaptation increasing temperatures highincome countries projections hotter future suggest without investment research risk management actions heatrelated morbidity mortality likely increasepmid34419205 doi101016 s01406736 21 012083,0.0
vesicle trafficking pathways neurodegeneration neurodegenerative diseases encompassing diverse range inherited sporadic disorders characterised progressive loss relatively discrete neuronal populations significant increasing challenge human health global economy 1 despite significant advances understanding underlying tiology diseases alzheimers parkinsons huntingtons intense efforts targeting development diseasemodifying therapies disorders majority people living neurodegenerative conditions prognosis remains poor 2 3 4 improving knowledge underlying causes neuronal loss disorders goal developing novel diseasemodifying therapies thus top priority research patient caregiver communitiesan area cell biology emerged past two decades key contributor events lead neuronal cell death across whole spectrum neurodegenerative disease vesicle trafficking 5 regulating formation degradation vesicles goes go happens fundamental function required cell viability 6 perhaps surprising dysfunction dynamic systems can result disease driven part rapid advances human genetics become clear neuronal cells exquisitely sensitive disruption vesicle trafficking wide range neurodegenerative diseases caused specific mutations genes contribute regulation vesicle traffickingto capitalise rapid increase research vesicle biology neurodegeneration threeday virtual meeting vesicle trafficking pathways neurodegeneration hosted wellcome connecting science may 17th 19th 2021 fig 1 goal meeting bring together researchers broad spectrum neurodegenerative disorders research including students early career researchers established scientists spanning clinical genetic cellular vivo translational biology industry order break barriers various groups searching areas common interest opportunities accelerate progress researchfig 1figure 1one first depictions intracellular vesicles within nervous system drawn camillo golgi used centre piece conference proceedings image courtesy university pavia full size imagelike many conferences scheduled past 18months original aim meeting held person case wellcome genome campus hinxton circumstances related covid19 pandemic however allow meeting held virtual event positive outcome opened attendance throughout world way possible person meeting attended 230 researchers representing 23 different countries divided sessions covering five broadlydefined areas related vesicle trafficking fig 2 alongside session focused neurogenetics vesicle trafficking well drug discovery panel discussing can drug vesicle trafficking processes within brainfig 2figure 2the five main cellular sessions held meeting image adapted reference https commonswikimediaorg wiki filecomplete_neuron_cell_diagram_ensvg image public domain full size imagethe conference bookended two outstanding keynote lectures first jennifer lippincottschwartz howard hughes medical institute janelia research campus describing exquisite resolution trafficking proteins endoplasmic reticulum golgi apparatus 7 second pietro de camilli yale university school medicine howard hughes medical institute covering recent investigations disruption vesicle trafficking linked neurodegenerative disease gene mutations notably linked vps13d 8 intervening sessions showcased incredibly exciting published unpublished research highlighting breadth depth research vesicular dysfunction neurodegeneration one aspect became obvious quite quickly somewhat arbitrary dividing lines different domains vesicular transport within cell used demarcate five biology sessions just somewhat arbitrary across sessions one observe common themes indeed common genetic contributors often acting across multiple different disorders making sense particular commonalities contrasting tiologies example vesicular dysfunction contributing frontal temporal dementia found amyotrophic lateral sclerosis frequently closelyrelated genetic defects 9 potential reveal important insights individuals develop one form brain disease rather anothertwo key challenges emerged presentations discussions conference neither unique neurodegeneration acutely obvious respects perhaps exacerbated complexities studying disorders central nervous system first sheer volume genetic clinical data now generated across neurological diseases presents huge task functional biology develop ever detailed understanding populationwide genetic risk large scale sequencing association studies expression analyses ever longer list potential risk genes investigate comprehend 10 regard striking majority presentations meeting involved investigating monogenic aspects neurodegenerative disease whether ultrastructure huntington disease intracellular inclusions disrupt endolysosomal function 11 function leucine rich repeat kinase 2 responding lysosomal damage 12 parkinson disease cite two examples topics covered short talks meeting moving monogeniccentric approach cell biology neurodegeneration making sense complexities common genetic risk neurodegeneration functional level gargantuan task one just beginning confrontedthe second major challenge translating advances understanding cellular processes driving disease clinical benefits patients despite notable recent successes example recent advances targeting spinal muscular atrophy 13 development drugs modify central nervous system disorders particular neurodegenerative diseases proved extremely challenging 14 15 taking dementia case study last two decades witnessed number promising preclinical drug candidates failing large human trials 16 exploiting increasing body knowledge relating vesicle trafficking dysfunction neurodegeneration presents major challenges least determining achieve specificity central nervous system measure biological activity human inherent challenges drugging pathways may require new approaches compound screening model development science therapeutics biomarker discovery subject discussion panel held part conference challenges however distract opportunities presented increasing diversity targets neurodegeneration new insights disease biology provided research areathe overriding impression conference taking account talks posters presented meeting feeling optimism future particular regard power technology drive insights fundamental biology vesicle trafficking understanding disease tiologyacross programme witness outstanding examples application highcontent screening 17 cryoelectron tomography 18 providing high volume information close atomic resolution coupled deep learning approaches applied increasingly large genetic biological datasets 19 heralds new era understanding events regulating vesicle trafficking cells central nervous system novel approaches silico imaging allow refinement experimental models 20 proteomewide investigations begin achieve level comprehensiveness comparable nucleic acidbased genomic analyses 21 clearly important area biology follow closely coming years,0.0
th17related cytokines potential discriminatory markers neuromyelitis optica devic#39 s disease multiple sclerosisa review int j mol sci 2021 aug 20 22 16 8946 doi 103390 ijms22168946abstractmultiple sclerosis ms devics disease nmo neuromyelitis optica autoimmune inflammatory diseases central nervous system cns etiology remains unclear serious limitation treatment diseases resemblance clinical pictures two conditions generates partial possibility introducing similar treatment hand high risk misdiagnosis therefore better understanding comparative characterization immunopathogenic mechanisms diseases essential improve discriminatory diagnosis effective treatment review special attention given th17 cells th17related cytokines context potential usefulness discriminatory markers ms nmo discussed results emphasize role th17 immune response ms nmo pathogenesis however considered without taking account broader perspective immune response mechanismspmid34445668 doi103390 ijms22168946,0.0
isolated cognitive relapses exist commentary cognitive impairment frequent patients multiple sclerosis pwms cognitive deficits worsen along disease contributing significant disability taking account heterogeneity among pwms however possibility acute cognitive change reported relapse includes physical symptoms full partial recovery13 besides concept proposed pardini et al4 relating isolated cognitive relapses icrs physical worsening based transient decrease symbol digit modalities test sdmt pwms debated sdmt assessing mainly information processing speed well validated ms clinically meaningful change proposed based ecological endpoint5 nevertheless pardini et al4 acknowledged limitations concerning choice definition icrs based one neuropsychological np assessment underlined icrs selfidentified highlighted value informant versions multiple sclerosis neuropsychological screening questionnaire msnq 6 interestingly pardini et al4 also supported clinical relevance icrs due association cognitive daily functioning cognitive decline pwmsbesides baldwin et al7 emphasized data published pardini et al4 came retrospective study small sample size fact unjustly concluded icrs exist whereas simply underrecognized patients physicians indeed one also wonder whether neurologists use tools identifying icrs practice importantly baseline followup relevant cognitive assessments needed able detect prospectively icrs clinical settingmoreover cognitive impairment driven cumulative brain inflammation ongoing neurodegeneration questionable concerning mechanisms leading icrs occurrence new ms lesions key relevant areas involved cognitive functions proposed supporting them4 one argue presence active inflammation also alter efficiency brain networks synaptic functioning drive decrease acute cognitive performance8 presence gadolinium enhancing gd+ lesion part definition disease activity ms used supporting cognitive relapse4 9 presence gd+ lesions means breakdown bloodbrain barrier reflect types inflammation within brain new grey matter lesions relevant cognition identified well diffuse inflammation microglial activation visualized conventional imagingso defended baldwin large data support attractive concept icrs longitudinal studies required confirm presence relevance icrs pwms controversy underlines absence consensual definition cognitive relapse highlights importance regular cognitive evaluations diagnosis ms followup visits clinical practice findings help disentangle important question future prognostic therapeutic implications pwmsdeclaration conflicting intereststhe author s declared following potential conflicts interest respect research authorship publication article ar reports personal fees nonfinancial support novartis personal fees research grants biogen personal fees research grant roche research grant genzyme personal fees research grant merck research grant bayer outside submitted work,0.0
role distinct subsets macrophages pathogenesis ms impact different therapeutic agents populations front immunol 2021 aug 20 12667705 doi 103389 fimmu2021667705 ecollection 2021abstractmultiple sclerosis ms demyelinating inflammatory disorder central nervous system cns besides vital role t cells immune cells including b cells innate immune cells macrophages ms also play critical role ms pathogenesis tissueresident ms brains parenchyma known microglia monocytederived ms enter cns following alterations cns homeostasis induce inflammatory responses ms although neuroprotective antiinflammatory actions monocytederived ms resident ms required maintain cns tolerance can release inflammatory cytokines reactivate primed t cells neuroinflammation cns ms patients elevated myeloid cells activated ms found associated demyelination axonal loss thus according role ms neuroinflammation attracted attention therapeutic target also due different origin location turnover strategies may require target various myeloid cell populations review role distinct subsets ms pathogenesis ms different therapeutic agents target cellspmid34489926 pmcpmc8417824 doi103389 fimmu2021667705,1.0
isolated cognitive relapses exist yes multiple sclerosis ms relapse defined transient neurological deficit lasting 24hours due concomitant conditions fever1 relapses acknowledged protean presentation motor sensory presentations clinical relevance thoroughly described association cognition relapses date still partially understoodindeed presence cognitive deficits motor sensory relapses reported least 1980s well recently systematic assessments ralph benedict collaborators 2 nature clinical relevance isolated cognitive relapses ie relapses characterized changes cognitive abilities received far less attentionsome evidence existence isolated cognitive relapses reported interesting study bellmannstrobl colleagues 20093 study authors showed presence gadolinium enhancing brain lesion gd+ ms subjects without novel sensory motor symptoms associated worse paced auditory serial addition test pasat performance compared later assessments suggested transient cognitive changes represent significant facet otherwise silent disease activity msour group proposed 2014 research definition isolated cognitive relapse operationalized 1 transient significant cognitive decline objective neuropsychological performance 2 without clinical subjective evidence new neurological signs symptoms 3 associated brain disease activity defined presence positive gd+ lesions time neuropsychological assessment4 compared usual clinical definition ms relapse criteria defining isolated cognitive relapse arguably stringent require evidence gd+ lesion time evaluationin 2014 retrospective study 17 relapsing remitting ms subjects 99 presented transient decline least 4 points symbol digit modalities test sdmt time magnetic resonance imaging mri compared evaluations completed preceding following 6months 99 subjects presented least gadolinium enhancing lesion novel sensorymotor deficits none showed significant changes fatigue levels affective symptomatologythe aforementioned impact gadolinium enhancing lesions cognitive performance confirmed groups thus increasing confidence results reported first study detail 2015 damasceno colleagues showed clinically stable ms patients presence gd+ lesions associated cognitive performance independently mri metrics cortical lesions corpus callosum damage 5 later fenu colleagues showed presence otherwise asymptomatic gd+ lesions associated loss practice effect serial cognitive evaluations6an open problem original work isolated cognitive relapses interpretation ecological relevance indeed choice 4point sdmt cutoff score based previous data association cognitive decline vocational activity changes arguably ideal evaluation relapses based analyses longterm data7 followup study showed isolated cognitive relapse patients presented increased cognitive difficulties daily activities evaluated informant using multiple sclerosis neuropsychological screening questionnaire8 line transient cognitive deficits also reported significant feature ms relapses selfreports qualitative study matza colleagues9despite findings key issues remain open characterization isolated cognitive relapses namely definition optimal neuropsychological protocol evaluation possible association mri metrics gd+ lesionsregarding development protocols detect isolated cognitive relapses clinical practice previous studies seems suggest sdmt informantbased multiple sclerosis neuropsychological screening questionnaire represent feasible approaches however subjects previously underwent formal neuropsychological assessments able define extent cognitive decline 4 8 indeed key feature proposed definition isolated cognitive relapse observation change performance compared previous evaluation ideally confirmed observation improvement performance followup assessments alas date fraction ms subjects routinely assessed cognitive standpoint thus argued increased attention isolated cognitive relapses lead much needed improvement care neuropsychological facets msa second open problem represented neural bases isolated cognitive relapses represent direct effect single new focal lesion white matter indeed previous work observed gd+ lesions frontal parietal territories likely associated changes sdmt isolated cognitive relapses rather lesions brain regions line proposed neural bases sdmt performance4 possible explanations transient isolated changes also possible including role newly formed grey matter lesions reduction synaptic efficiency independent development new lesions indeed regarding last hypothesis presence active inflammation independent lesions shown hippocampus ms subjects experimental autoimmune encephalitis associated functional regional changes10 observations suggest experimental work order increase understanding isolated cognitive relapses point need maintain least time prudent stance attribution cognitive performance fluctuations cognitive relapses absence mri evidence gd+ lesions despite available evidence point existence transient changes neuropsychological performance subjects ms associated reduction daily cognitive activities presence newly formed white matter lesionsdeclaration conflicting intereststhe author s declared following potential conflicts interest respect research authorship publication article m pardini partly supported university genoa curiositydriven grant m pardini receives research support novartis nutricia received fees novartis merck biogenfundingthe author s disclosed receipt following financial support research authorship publication article work developed within framework dinogmi department excellence miur 20182022 legge 232 del 2016 supported grant italian ministry health neuroscience network,0.0
electroencephalographic evidence gray matter lesions among multiple sclerosis patients casecontrol study medicine baltimore 2021 aug 20 100 33 e27001 doi 101097 md0000000000027001abstractthis study aimed investigate evidence gray matter brain lesions multiple sclerosis ms patients evaluating resting state alpha rhythm brain electrical activitythe study included 50 patients diagnosed ms recruited ms clinic 50 age gendermatched control participants study investigated parameters posterior dominant rhythm pdr electroencephalography eeg recordings including wave frequency amplitude functional disability among patients evaluated according expanded disability status scale univariate statistical analysis completed using oneway analysis variance t test p value less 05 indicate statistical significancepatients ms significantly lower pdr frequency amplitude values compared controls p value 01 34 ms patients pdr frequency less 85 hz pdr frequency negatively associated level functional disability among patients p value 001 4 patients abnormal epileptiform dischargesbackground slowing resting alpha rhythms epileptiform discharges suggestive gray matter degeneration may help prediction followup cortical damage functional disabilities among ms patients therefore electroencephalography monitoring pdr spectrum may serve alternative complementary tool imaging techniques detect monitor cerebral cortical lesionspmid34414988 doi101097 md0000000000027001,0.0
cognition disease characteristics adult onset versus late onset multiple sclerosis abstractbackgroundcognitive impairment common sequelae multiple sclerosis ms however relatively little known cognitive impairment lateonset multiple sclerosis loms objectiveto investigate differences disease characteristics cognition loms adultonset multiple sclerosis aoms patientsmethodsarchival medical records neuropsychological evaluations ms specialty center reviewed differences disease characteristics 53 loms 124 aoms compared using chisquare analysis variance anova investigate differences cognitive functioning ageadjusted standardized scores compared via analysis covariance ancova using cardiac risk factors disease duration covariatesresultscompared aoms loms patients significantly cardiac risk factors shorter disease duration shorter time diagnosis loms patients similar expanded disability status scale scores aoms patients loms patients demonstrated significantly impairment tasks visual learning memory working memory aoms patientsconclusiondespite shorter disease duration loms aoms patients similar levels physical impairment however even accounting differences disease duration cardiac risk loms patients showed greater burden cognitive impairment aoms patients suggesting ms diagnosed later life may progress faster due interaction ms neuropathology aging,0.0
sodium valproate increases activity sirtuin pathway resulting beneficial effects spinocerebellar ataxia3 vivo machadojoseph disease mjd also known asspinocerebellar ataxia type 3 fatalneurodegenerativedisease thatimpairscontroland coordination movementhere tested whether treatment histo,0.0
cellfree stem cellderived extract formulation treatment knee osteoarthritis study protocol preliminary nonrandomized openlabel multicenter feasibility safety study background musculoskeletal conditions highly prevalent knee oa common current treatment modalities limitations either fail solve underlying pathophysiology highly invasive address limitations attention focused use biologics efficacy devices attributed presence growth factors gfs cytokines cks extracellular vesicles evs mind formulated novel cellfree stem cellderived extract ccm human progenitor endothelial stem cells hpescs preliminary study demonstrated presence essential components regenerative medicine namely gfs cks evs including exosomes ccm proposed study aims evaluate safety efficacy intraarticular injection novel cellfree stem cellderived extract ccm treatment knee oamethods analysisthis nonrandomized openlabel multicenter prospective study safety efficacy intraarticular ccm patients suffering grade ii iii knee oa will evaluated 20 patients grade ii iii oa meet inclusion exclusion criteria will consented screened recruit 12 patients receive treatment study will conducted 2 sites within usa 12 participants will followed 24 months study participants will monitored adverse reactions assessed using numeric pain rating scale nprs patientreported outcomes measurement information system promis score knee injury osteoarthritis outcome score jr koos jr 36ietm short form survey sf36 single assessment numeric evaluation sane physical exams plain radiography magnetic resonance imaging mri magnetic resonance observation cartilage repair tissue mocart score improvements pain function satisfaction cartilage regenerationdiscussionthis prospective study will provide valuable information safety efficacy intraarticular administration cellfree stem cellderived extract ccm patients suffering grade ii iii knee oa outcomes initial study novel ccm will lay foundation larger randomized placebocontrolled multicenter clinical trial intraarticular ccm symptomatic knee oatrial registrationregistered july 21 2021 clinicaltrialsgov nct04971798,0.0
potential roles extracellular vesicles biomarkers novel treatment approach multiple sclerosis int j mol sci 2021 aug 20 22 16 9011 doi 103390 ijms22169011abstractextracellular vesicles evs heterogeneous group bilayer membranewrapped molecules play important role celltocell communication participating many physiological processes pathogenesis several diseases including multiple sclerosis ms recent years many studies focused evs promising results indicating potential role biomarkers ms helping us better understand pathogenesis disease recent evidence suggests novel subpopulations evs according cell origin derived cells belonging nervous immune systems providing information regarding inflammation demyelination axonal damage astrocyte microglia reaction bloodbrain barrier permeability leukocyte transendothelial migration ultimately synaptic loss neuronal death ms biomarkers can also provide insight disease activity progression can differentiate patients disease phenotype information can enable new pathways therapeutic target discovery consequently development novel treatments recent evidence also suggests current disease modifying treatments dmts ms modify levels content circulating evs evs might also serve biomarkers help monitor response dmts improve medical decisions concerning dmt initiation choice escalation withdrawal furthermore evs act biomarkers also treatment brain repair immunomodulation ms evs considered excellent delivery vehicles studies progress show evs containing myelin antigens play pivotal role inducing antigenspecific tolerance autoreactive t cells novel strategy treatment evbased vaccines ms review explores breakthrough role nervous immune system cellderived evs markers pathological disease mechanisms potential biomarkers treatment response ms addition review explores novel role evs vehicles antigen delivery therapeutic vaccine restore immune tolerance ms autoimmunitypmid34445717 doi103390 ijms22169011,1.0
pregnancy women multiple sclerosis france 2010 2015 incidence outcomes exposure diseasemodifying therapies abstractbackgroundmultiple sclerosis ms usually diagnosed 2040 years old women often plan childrenobjectiveour objectives estimate pregnancy incidence rates women multiple sclerosis ms describe use diseasemodifying therapies dmts conception pregnancy pregnancy outcomesmethodsthis retrospective cohort study included 15 49yearold women ms french national health insurance database 20102015 pregnancy exposed dmt reimbursement claim occurred pregnancy 14 preceding days used zeroinflated negative binomial zinb regression models estimate incidence rates ordinal multinomial regression models estimate dmt exposure pregnancy outcomesresultsthe pregnancy incidence rate 45 per 100 personyears probability dmtexposed pregnancy increased 022 2010 030 2015 probability live birth 072 95 ci070074 exposed pregnancies varied considerably among dmts 077 95 ci076079 without treatment 081 95 ci079083 treatment stopped within previous yearconclusionin populationbased study showed increase exposed pregnancies time betainterferon glatiramer acetate used dmts associated highest probabilities live birth interrupted exposed pregnancies may reflect undesired pregnancies fear adverse outcome recent dmt stop probably reflects pregnancy planning,0.0
anticentromere antibody induced immunization centromere protein freunds complete adjuvant may interfere mouse earlystage embryo background anticentromere antibody aca member antinuclear antibody spectrum anas speculated associated subfertility thus present study aimed investigate induction aca production potential interference earlystage embryosmethodsrecombinant centromere proteina cenpa centromere proteinb cenpb complete freunds adjuvant cfa used immunize mice serum aca level evaluated using indirect immunofluorescence test immunofluorescence assay performed detect igg follicles ovarian tissues earlystage embryosresultsfollowing treatment serum positive aca observed mice treated cenp cfa furthermore igg detected follicular fluid earlystage embryos mice treated cenp cfaconclusionsthis study preliminarily indicated aca induced cenp cfa may penetrate living embryos earlystage mice,0.0
cortical involvement leptomeningeal inflammation myelin oligodendrocyte glycoprotein antibody disease threedimensional fluidattenuated inversion recovery mri study abstractbackgroundcortical demyelination meningeal inflammation detected neuropathologically multiple sclerosis ms recently myelin oligodendrocyte glycoprotein antibody disease mogad objectivesto assess vivo cortical leptomeningeal involvement mogadmethodswe prospectively evaluated 11 mogad 12 relapsingremitting ms rrms patients combining threedimensional fluidattenuated inversion recovery 3dflair 3dt1weighted 3dt1w sequences 3tesla magnetic resonance imaging mri leptomeningeal contrast enhancement lmce assessed 3dflair postgadolinium 3dflairgd cerebral cortical lesions ccls classified either intracorticalsubpial icsp leukocortical lc resultsccls present 8 11 mogad 12 12 rrms patients number ccls significantly lower mogad median interquartile range iqr 3 054 vs 12 47519 p00032 mogad icsp lesions slightly prevalent lc lesions 2 025 vs 1 02 p06579 whereas rrms icsp lesions less prevalent lc lesions 35 27555 vs 9 21275 p027 lmce observed 3 11 mogad 1 12 rrms patients mogad lmce showed increased median number ccls compared mogad without lmce 8 49 vs 25 075325 p034 correlation observed mogad mri findings mogad duration b serum mogimmunoglobulin g1 titers c oligoclonal band presenceconclusionwe described cortical lesion topography detected first time lmce using 3dflairgd sequences mogad patients,1.0
icariin upandcoming bioactive compound neurological diseases network pharmacologybased study literature review drug des devel ther 2021 aug 20 1536193641 doi 102147 dddts310686 ecollection 2021abstracticariin biologically active substance epimedii herba used treatment neurologic disorders however comprehensive analysis molecular mechanisms icariin lacking review present brief history use icariin medicinal purposes describe active chemical components epimedii herba examine evidence experimental studies uncovered molecular targets icariin different diseases also constructed proteinprotein interaction network carried gene ontology kyoto encyclopedia genes genomes functional enrichment analyses predict therapeutic actions icariin nervous system diseases including alzheimer disease parkinson disease ischemic stroke depressive disorder multiple sclerosis glioblastoma hereditary spastic paraplegias results analyses can guide future studies application icariin treatment neurologic disorderspmid34447243 pmcpmc8384151 doi102147 dddts310686,0.0
discovery novel biomarkers diagnosing predicting progression multiple sclerosis using tmtbased quantitative proteomics front immunol 2021 aug 20 12700031 doi 103389 fimmu2021700031 ecollection 2021abstractobjective aimed identify protein biomarkers rapidly accurately diagnose multiple sclerosis ms using highly sensitive proteomic immunoassaymethods tandem mass tag tmt quantitative proteomic analysis performed determine differentially expressed proteins deps cerebrospinal fluid csf samples collected 10 patients ms 10 noninflammatory neurological controls nincs deps analyzed using bioinformatics tools candidate proteins validated using elisa method another cohort comprising 160 samples paired csf plasma 40 patients ms csf 40 nincs plasma 40 healthy individuals receiver operating characteristic roc curves used determine diagnostic potential methodresults compared nincs identified 83 csfspecific deps total 343 proteins ms patients gene ontology go enrichment analysis revealed deps mainly involved platelet degranulation negative regulation proteolysis posttranslational protein modification pathway enrichment analysis revealed complement coagulation cascades ras signaling pathway pi3kakt signaling pathway main components insulinlike growth factorbinding protein 7 igfbp7 insulinlike growth factor 2 igf2 somatostatin sst identified potential proteins high scores degree centrality proteinprotein interaction ppi network validated expression three proteins using elisa compared nincs level csf igfbp7 significantly upregulated level csf sst significantly downregulated ms groupconclusion results suggest sst igfbp7 might associated pathogenesis ms helpful diagnosing ms since igfbp7 used classify relapsing remitting ms rrms secondary progressive ms spms patients therefore may act potential key marker therapeutic target mspmid34489947 pmcpmc8417809 doi103389 fimmu2021700031,0.0
adaptive immunity risk autoreactivity covid19 int j mol sci 2021 aug 20 22 16 8965 doi 103390 ijms22168965abstractwhile first foremost considered respiratory infection covid19 can result complications affecting multiple organs immune responses covid19 can protect disease well drive insights responses specifically targets recognised immune system vital importance understanding side effects covid19 associated pathologies bodys adaptive immunity recognises responds specific targets antigens expressed foreign pathogens usually target selfantigens however immune system becomes dysfunctional adaptive immune cells can react selfantigens can result autoimmune disease viral infections well reported associated exacerbate autoimmune diseases multiple sclerosis ms systemic lupus erythematosus sle covid19 patients new onset ms sle well occurrence autoimmunelike pathologies reported additionally presence autoantibodies without known associations autoimmune diseases found herein describe mechanisms virally induced autoimmunity summarise emerging reports autoimmunelike diseases autoreactivity reported associated sarscov2 infectionpmid34445670 doi103390 ijms22168965,0.0
regional grey matter microstructural changes volume loss according disease duration multiple sclerosis patients sci rep 2021 aug 19 11 1 16805 doi 101038 s4159802196132xabstractthe spatiotemporal characteristics grey matter gm impairment multiple sclerosis ms poorly understood used new surfacebased diffusion mri processing tool investigate regional modifications microstructure quantified volume loss gm cohort patients ms classified three groups according disease duration additionally investigated relationship gm changes disease severity studied 54 healthy controls 247 ms patients classified regarding disease duration ms1 less 5 years n 67 ms2 515 years n 107 ms3 than15 years n 73 compared gm mean diffusivity md fractional anisotropy fa volume groups estimated clinical associations regional modifications diffusion measures md fa volume overlap early disease became widespread later phases found higher md ms1 group mainly temporal cortex volume reduction deep gm left precuneus additional md changes evident cingulate occipital cortices ms2 group coupled volume reductions deep gm parietal frontal poles changes md volume extended 80 regions ms3 group conversely increments fa low effect size observed parietal cortex thalamus ms1 ms2 groups extended frontal lobe later group md gm changes associated white matter lesion load physical cognitive disability microstructural integrity loss atrophy present differential spatial predominance early ms accrual time probably due distinct pathogenic mechanisms underlie tissue damagepmid34413373 doi101038 s4159802196132x,0.0
macroscopic detection demyelinated lesions mouse pns neutral red dye sci rep 2021 aug 19 11 1 16906 doi 101038 s41598021963954abstractlysophosphatidylcholine lpc induced demyelination versatile animal model frequently used identify examine molecular pathways demyelination remyelination central cns peripheral nervous system pns however identification focally demyelinated lesion difficult usually required tissue fixation sectioning histological analysis recently method labeling identification demyelinated lesions cns intraperitoneal injection neutral red nr dye developed however remained unknown whether nr can used label demyelinated lesions pns study generated lpcinduced demyelination sciatic nerve mice demonstrated demyelinated lesions site lpc injection readily detectable 7 days postlesion dpl macroscopic observation nr labeling moreover nr staining gradually decreased 7 21 dpl course remyelination electron microscopy analysis nrlabeled sciatic nerves 7 dpl confirmed demyelination myelin debris lesions furthermore fluorescence microscopy showed nr colabeling activated macrophages schwann cells pns lesions together nr labeling straightforward method allows macroscopic detection demyelinated lesions sciatic nerves lpc injectionpmid34413421 doi101038 s41598021963954,1.0
demyelinating disease central nervous system concurrent covid19 cureus 2021 aug 19 13 8 e17297 doi 107759 cureus17297 ecollection 2021 augabstractneurological diseases related coronavirus disease2019 covid19 increasingly reported report three cases presented subtle neurologic findings manifesting within range 15 days four months covid19 diagnoses magnetic resonance imaging showed acute multifocal periventricular subcortical demyelinating lesions lesions showed contrast enhancement diffusion restriction severe acute respiratory syndrome coronavirus 2 sarscov2 pcr found cerebrospinal fluid just one patient patients received intravenous methylprednisolone therapy report aim discuss aspects possible covid19related demyelination support diagnosis multiple sclerosis ms acute disseminated encephalomyelitis adem pmid34552833 pmcpmc8449512 doi107759 cureus17297,1.0
cognitive fatigability fatigue predicts employment status patients ms three months rehabilitation abstractbackground fatigue potentially important factor causing unemployment people multiple sclerosis pwms widely accepted discrimination fatigue subjective sensation fatigability objective measure change performance aim study identify whether cognitive fatigue cognitive fatigability better predictor employment status three months discharge neurological rehabilitation centermethods 64 pwms mean age 489 43 females mean time since diagnosis 147 years median expanded disability status scale edss 38 complaining fatigue reporting difficulties working capacity participated cognitive loading task inpatient rehabilitation reaction time performance measured using standardized alertness test tapm tonic alertness measured 8am 11am 2pm patients worked standardized test battery morning lunch induce fatigability completed fatigue scale motor cognition fsmc standardized questionnaire rate trait component cognitive motor fatigue employment status rated within standardized interview phone three months discharge clinicresults mean cognitive fatigue according fsmc 389 74 mean motor fatigue 410 56 indicating severe cognitive motor fatigue 15 88 17 patients working fulltime severe fatigue according fsmc cognitive subscale fsmc fsmc cognition correlate rs084 p512 motor subscale fsmc fsmc motor correlated rather weakly significantly rs 220 p080 employment status contrast significant medium correlation alertness 8am alertness1 employment status rs304 p014 ordered logistic regression revealed alertness1 alertness difference afternoon noon alertness difference32 predicted significantly employment status fsmc motor cognition subscales predictive value employmentconclusion cognitive fatigability tonic alertness 8am increase reaction time afternoon adequate predict employment status pwms three months discharge clinic subjective sensation fatigue determined fsmc,0.0
proceedings joint meeting 126th annual meeting japanese association anatomists 98th annual meeting physiological society japan n,0.0
cannabis sativa melatonin alter brain lipid alter oxidative mechanisms female rats background lipid profile redox status play role brain dys functions cannabinoid melatonergic systems operate brain contribute brain patho physiology roles modulation brain lipid redox status wellknown studied effect ethanol extract cannabis sativa cs melatonin m lipid profile antioxidant system rat brainmethodswe randomly divided twentyfour 24 female wistar rats 4 groups n 6 rats group 1 control received distilled water mixed dmso groups iiiv received cs 2 mg kg m 4 mg kg coadministration cs m cs + m respectively via oral gavage 800 1000 daily 14 days animals underwent 12h fasting last day treatment sacrificed ketamine anesthesia 20 mg kg im brain tissues excised homogenized assay concentrations total cholesterol tc triacylglycerol tg highdensity lipoprotein cholesterol hdlc nitric oxide malondialdehyde mda activities glucose6phosphate dehydrogenase g6pd glutathione reductase gr glutathione peroxidase gpx catalase cat superoxide dismutase sod acetylcholinesterase ache oneway analysis variance anova used compare means across groups followed least significant difference lsd posthoc testresultscs m affect lipid profile parameters however cs increased g6pd 1558 109 2102 145 u l p 0047 gpx 1047 086 1771 104 u l p 0019 sod 081 002 090 001 m p 0007 decreased 940 051 675 021 m p 0010 effect mda p 0905 cat p 0831 gr p 0639 ache p 0571 comparison control group m augmented increase g6pd 2102 145 u l 2718 181 u l p 0032 decrease 675 021 486 013 m p 0034 abolished increase gpx 1771 104 859 206 u l p 0006 sod 090 001 070 000 m p 0000 elicited cs rat brain comparison cs groupconclusionscs m alter brain lipid profile data support contention cs elicits antioxidative effect brain tissue cs + m elicits prooxidant effect rat brain,0.0
microglial transcriptome analysis rnls8 mouse model tdp43 proteinopathy reveals discrete expression profiles associated neurodegenerative progression recovery abstractthe microglial reaction hallmark neurodegenerative conditions elements thereof may exert differential effects disease progression either worsening ameliorating severity amyotrophic lateral sclerosis als syndrome characterized cytoplasmic aggregation tdp43 protein atrophy motor neurons cortex spinal cord transcriptomic signatures microglia disease progression incompletely understood performed longitudinal rnaseq analysis cortical spinal cord microglia rnls8 mice doxycyclineregulatable expression human tdp43 htdp43 cytoplasm neurons recapitulates many features als transgene suppression rnls8 mice leads functional anatomical electrophysiological resolution dependent microglial reaction concurrent recovery rather disease onset identified basal differences gene expression profiles microglia dependent localization spinal cord cortex microglia subjected chronic htdp43 overexpression demonstrated transcriptomic changes locations noted strong upregulation apoe axl cd63 clec7a csf1 cst7 igf1 itgax lgals3 lilrb4 lpl spp1 late disease recovery importantly identified distinct suite differentially expressed genes associated phase disease progression recovery differentially expressed genes associated chemotaxis phagocytosis inflammation production neuroprotective factors data provide new insights microglial reaction tdp43 proteinopathy genes differentially expressed progression recovery may provide insight unique instance microglial reaction promotes functional recovery neuronal insult,1.0
myelin basic protein expression thymoma methylprednisolone administration multiple sclerosis respirol case rep 2021 aug 19 9 9 e0834 doi 101002 rcr2834 ecollection 2021 sepabstractthe relationship thymic epithelial tumour demyelinating disease dd unknown surgical resection optimized 39yearold woman administrated methylprednisolone newly diagnosed multiple sclerosis thymic tumour found anterosuperior mediastinum via computed tomography chest videoassisted thoracoscopic thymectomy performed histologically tumour diagnosed type ab thymoma immunohistochemical staining showed positive myelin basic protein mbp cytosol spindle cells tumour specimen germinal centres lymphocytes infiltration noted ectopic mbp presentation thymoma might correlated ddpmid34457311 pmcpmc8374605 doi101002 rcr2834,1.0
mtorc1grasp55 signaling axis controls unconventional secretion reshape extracellular proteome upon stress mol cell 2021 jul 5s10972765 21 004974 doi 101016 jmolcel202106017 online ahead printabstractcells communicate environment via surface proteins secreted factors unconventional protein secretion ups evolutionarily conserved process via distinct cargo proteins secreted upon stress ups types depend upon golgiassociated grasp55 protein however regulation biological role remain poorly understood show mechanistic target rapamycin complex 1 mtorc1 directly phosphorylates grasp55 maintain golgi localization thus revealing physiological role mtorc1 organelle stimuli inhibit mtorc1 cause grasp55 dephosphorylation relocalization ups compartments multiple unbiased proteomic analyses identify numerous cargoes follow unconventional secretory route reshape cellular secretome surfactome using mmp2 secretion proxy ups provide important insights regulation physiological role collectively findings reveal mtorc1grasp55 signaling hub integration point stress signaling upstream ups key coordinator cellular adaptation stresspmid34245671 doi101016 jmolcel202106017,0.0
immunoresponsive gene 1 modulates severity brain injury cerebral ischaemia brain commun 2021 aug 19 3 3 fcab187 doi 101093 braincomms fcab187 ecollection 2021abstractinflammatory stimuli induce immunoresponsive gene 1 expression turn catalyses production itaconate diverting cisaconitate away tricarboxylic acid cycle immunoregulatory effect immunoresponsive gene 1 itaconate axis recently documented lipopolysaccharideactivated mouse human macrophages addition dimethyl itaconate itaconate derivative reported ameliorate disease severity animal models psoriasis multiple sclerosis currently whether immunoresponsive gene 1 itaconate axis exerts modulatory effect ischaemic stroke remains unexplored study investigated whether immunoresponsive gene 1 plays role modulating ischaemic brain injury addition molecular mechanism underlying protective effects immunoresponsive gene 1 ischaemic stroke elucidated results showed immunoresponsive gene 1 highly induced ischaemic brain following ischaemic injury interestingly found irg1 stroke animals exhibited exacerbated brain injury displayed enlarged cerebral infarct compared wildtype stroke controls furthermore irg1 stroke animals presented aggravated bloodbrain barrier disruption associated augmented evans blue leakage increased immune cell infiltrates ischaemic brain moreover irg1 stroke animals displayed elevated microglia activation demonstrated increased cd68 cd86 iba1 expression analysis revealed immunoresponsive gene 1 induced microglia ischaemic stroke deficiency immunoresponsive gene 1 resulted repressed microglial heme oxygenase1 expression exacerbated ischaemic brain injury notably administration dimethyl itaconate compensate deficiency immunoresponsive gene 1 itaconate axis led enhanced microglial heme oxygenase1 expression alleviated ischaemic brain injury improved motor function decreased mortality irg1 stroke animals summary demonstrate first time induction immunoresponsive gene 1 microglia following ischaemic stroke serves endogenous protective mechanism restrain brain injury heme oxygenase1 upregulation thus findings suggest targeting immunoresponsive gene 1 may represent novel therapeutic approach treatment ischaemic strokepmid34557667 pmcpmc8453405 doi101093 braincomms fcab187,0.0
identification potential inhibitors epsteinbarr virus nuclear antigen 1 ebna1 insight docking molecular dynamic simulations acs chem neurosci 2021 aug 2 doi 101021 acschemneuro1c00350 online ahead printabstractepsteinbarr virus ebv known tumorigenic virus associated various neuropathies including multiple sclerosis ms however antiebv fdaapproved drug available market study targeted ebv protein ebv nuclear antigen 1 ebna1 crucial virus replication expressed stages viral latencies dimeric protein binds 18 bp palindromic dna sequence initiates process viral replication chose phytochemicals fdaapproved ms drugs based literature survey followed evaluation efficacies antiebna1 molecules molecular docking revealed fda drugs ozanimod siponimod teriflunomide phytochemicals emodin protoapigenone egcg bound ebna1 high affinities admet lipinskis rule analysis phytochemicals predicted favorable druggability supported assessments pocket druggability molecular dynamics simulations binding affinity predictions molecular mechanics generalized born surface area mm gbsa method results establish stable binding siponimod ozanimod ebna1 mainly via van der waals interactions identified hot spot residues like i481 k477 l582 k586 binding ligands particular k477 amino terminal ebna1 known establish interaction two bases major groove dna siponimod bound ebna1 engaging k477 thus plausibly making unavailable dna interaction computational alanine scanning supported significant roles k477 i481 k586 binding ligands ebna1 conclusively compounds showed promising results used ebna1pmid34340305 doi101021 acschemneuro1c00350,0.0
55yearold japanese man multiple sclerosis diagnosed disseminated tuberculosis identified liver function abnormalities case report j case rep 2021 aug 18 22e931369 doi 1012659 ajcr931369abstractbackground reactivation latent tuberculosis infection ltbi recognized complication immunosuppressive treatment however immunosuppressed patients also risk hematogenous disseminated spread primary infection mycobacterium tuberculosis report presents case 55yearold japanese man 12year history multiple sclerosis hospitalized worsening neurological symptoms diagnosed disseminated tuberculosis identified abnormalities liver function test results case report 55yearold japanese man admitted hospital treatment multiple sclerosis worsening symptoms showed mild liver dysfunction time admission laparoscopy biopsy performed identify cause liver dysfunction positive finding liver surface studded yellowishwhite nodular lesions histological examination liver biopsy specimen revealed granuloma without caseous necrosis patient suspected tuberculosis although results interferonreleasing assay indeterminate asymptomatic disseminated tuberculosis diagnosed serum adenosine deaminase levels caseating granuloma cervical lymph node detection acidfast bacilli dna cervical lymph nodes polymerase chain reaction tuberculin skin test findings antituberculosis treatment led improvement liver function test findings conclusions case highlighted tuberculosis may atypical presentation immunosuppressed patient addition reactivation ltbi hematogenous spread primary tuberculosis may result disseminated disease involving multiple organs requiring emergency treatmentpmid34404756 doi1012659 ajcr931369,0.0
accommodative amplitudes highorder aberrations patients multiple sclerosis optic nerve nvolvement abstract purpose study aimed investigate compare changes corneal aberrations accommodative amplitudes patients multiple sclerosis normal individuals methods included 20 patients previously diagnosed multiple sclerosis optic nerve involvement multiple sclerosis group 20 healthy sex agematched individuals control group selected 40 years old accommodation individuals 40 years old significantly deteriorates measured accommodative amplitude diopters minus lens test evaluated higherorder aberrations using idesign aberrometer compared accommodative amplitude root mean square higherorder aberrations groups results mean age multiple sclerosis control groups 3525 452 3228 683 years respectively p0170 accommodative amplitude 405 125 d multiple sclerosis group 600 103 d control group statistically significant difference p0001 meanwhile root mean square higherorder aberrations significantly different groups multiple sclerosis group 044 022 control group 043 010 p0824 moreover aberration changes statistically significant differences two groups baseline 5 d stimulus conclusions accommodative amplitude decreased patients multiple sclerosis suggesting possible cause transient visual impairments patients however accommodative amplitude demonstrate significant difference terms higherorder aberration change accommodation patients controls,0.0
modified arteriosclerosis score predicts outcomes diabetic kidney disease background significance renal arteriosclerosis prediction renal outcomes diabetic kidney disease dkd remains undeterminedmethodswe enrolled 174 patients dkd three centres january 2010 july 2017 severity extent arteriosclerosis analysed sections based dual immunohistochemical staining cd31 smooth muscle actin xtile plot used determine optimal cutoff value primary endpoint renal survival rs defined duration renal biopsy endstage renal disease deathresultsthe baseline estimated glomerular filtration rate egfr 135 qualified patients 45 29 70 ml min per 173 m2 average 24h urine protein 452 245 766 g 24 h number glomeruli biopsy specimens 2107 97 proportion severe arteriosclerosis kidney positively correlated renal pathology society glomerular classification r 028 p 0012 interstitial fibrosis tubular atrophy ifta r 039 p 0001 urine protein r 0213 p 0013 systolic bp r 0305 p 0000 age r 0220 p 0010 significantly negatively correlated baseline egfr r 0285 p 0001 multivariable model primary outcomes significantly correlated glomerular class hr 172 ci 115 257 ifta hr 196 ci 126 306 modified arteriosclerosis score hr 221 ci 118 413 risk adjustment rs independently associated baseline egfr hr 097 ci 096 098 urine proteinuria hr 110 ci 104 117 modified arteriosclerosis score hr 201 ci 110 367 nomogram exhibited good calibration acceptable discrimination cindex 082 ci 075 087 conclusionsthe severity proportion arteriosclerosis may helpful prognostic indicators dkd,0.0
implementation incorporated health technology assessments united kingdom systematic rapid review abstractobjectiveshealth interventions clinical setting may complex particularly true clinical interventions require systems reorganization behavioural change implementation involves additional challenges captured within clinical trial setting medical research council guidance complex interventions highlights need consider economic evaluation alongside implementation however extent guidance adhered unclear failure incorporate implementation within evaluation intervention may hinder translation research findings routine practice will consequences patient care study examined methods used address implementation within health research conducted funding national institute health research nihr health technology assessment hta programmemethodswe conducted rapid review using systematic approach included nihr hta monographs contained word implementation within title abstract published 2014 2020 assessed studies according existing recommendations specifying reporting implementation approaches research additional themes included recommendation particular relevance research question also identified summarized narrative synthesisresultsthe extent implementation formally incorporated defined varied among studies methods examining implementation ranged single stakeholder engagement events comprehensive process evaluation obvious pattern whether approaches implementation evolved recent years approximately 50 22 42 studies included economic evaluation two studies included use qualitative data obtained within study quantitatively inform aspects relating implementation economic evaluation studydiscussiona variety approaches identified incorporating implementation within hta however go far enough terms incorporating implementation actual design evaluation ensure implementation clinically effective costeffective interventions propose guidance incorporate implementation within complex interventions required incorporating implementation economic evaluation provides step direction,0.0
multiple sclerosis therapy consensus group mstcg position statement diseasemodifying therapies multiple sclerosis white paper ther adv neurol disord 2021 aug 18 1417562864211039648 doi 101177 17562864211039648 ecollection 2021abstractmultiple sclerosis complex autoimmunemediated disease central nervous system characterized inflammatory demyelination axonal neuronal damage approval various diseasemodifying therapies increased understanding disease mechanisms evolution recent years significantly changed prognosis course disease update multiple sclerosis therapy consensus group treatment recommendation focuses important recommendations diseasemodifying therapies multiple sclerosis 2021 recommendations based current scientific evidence apply medications approved wide parts europe particularly germanspeaking countries germany austria switzerland pmid34422112 pmcpmc8377320 doi101177 17562864211039648,1.0
effect aerobic exercise neurofilament light chain glial fibrillary acidic protein level patients relapsing remitting type multiple sclerosis abstractbackground multiple sclerosis ms autoimmune neurodegenerative disease central nervous system disease activity can monitored biomarkers aim study investigate serum glial fibrillary acidic protein gfap neurofilament light chain nfl relapsingremitting ms rrms patients aerobic exercisemethods total 38 participants rrms expanded disability status scale 10 45 randomized study group 3 week 8 weeks 60 70 maximal aerobic capacity vo2max +home exercises control group given home exercises programme 3 times week 8 week serum nfl gfap levels analyzed using enzymelinked immunosorbent analysis method end 8 weeksresults nfl gfap levels statistically lower study group end study study control group significant changes observed serum nfl gfap levels nfl levels significantly higher study group control groupconclusion shown first time serum gfap nfl levels 10 32 respectively rrms patients decreased aerobic exercise study important terms investigating effects aerobic exercise individuals rrms elucidating underlying measurable biomarkers significant reduction nfl gfap important role pathology associated nervous system damage ms aerobic exercise may promising understanding regulation disease activity ms patients,0.0
direct differentiation tonsillar biopsyderived stem cells neuronal lineage background neurological disorders considered one greatest burdens global public health leading cause death stem cell therapies hold great promise cure neurological disorders stem cells can serve cell replacement also secreting factors enhance endogenous tissue regeneration adult human multipotent stem cells mscs reside blood vessels therefore can found many tissues throughout body including palatine tonsils several studies reported capacity mscs differentiate among cell types neuronal lineage however unlike case embryonic stem cells unclear whether mscs can develop mature neuronsmethodshuman tonsillar mscs tmscs isolated small 06g sample tonsillar biopsies high viability yield recently reported cells differentiated rapid multistage procedure committed postmitotic neuronlike cells using defined conditionsresultshere describe first time derivation differentiation tonsillar biopsyderived mscs tmscs rapid multistep protocol postmitotic neuronlike cells using defined conditions without genetic manipulation characterized tmscderived neuronal cells demonstrate robust differentiation vitroconclusionsour procedure leads rapid neuronal lineage commitment loss stemness markers early three days following neurogenic differentiation studies identify biopsyderived tmscs potential source generating neuronlike cells may potential use vitro modeling neurodegenerative diseases cell replacement therapies,0.0
regional white matter scaling human brain anatomical organization primate cortex varies function total brain size possession larger brain accompanied disproportionate expansion associative cortices alongside relative contraction sensorimotor systems however equivalent scaling maps yet available regional white matter anatomy use three largescale neuroimaging datasets examine regional white matter volume wmv scales interindividual variation brain volume among typically developing humans combined n 2391 1247 females 1144 males show wmv scaling regionally heterogeneous larger brains relatively greater wmv anterior posterior regions cortical white matter well genu splenium corpus callosum relatively less wmv subcortical regions furthermore regions positive wmv scaling tend connect previouslydefined regions positive gray matter scaling cortex revealing coordinated coupling regional gray white matter organization naturally occurring variations human brain size however also show two commonly studied measures white matter microstructure fractional anisotropy fa magnetization transfer mt scale negatively brain size manner spatially unlike wmv scaling collectively findings provide complete view anatomic scaling human brain offer new contexts interpretation regional white matter variation health diseasesignificance statement recent work shown humans regional cortical subcortical anatomy show systematic changes function brain size variation show regional white matter structures also show brainsize related changes humans specifically white matter regions connecting higherorder cortical systems relatively expanded larger human brains subcortical cerebellar white matter tracts responsible unimodal sensory motor functions relatively contracted regional scaling white matter volume wmv coordinated regional scaling cortical anatomy distinct scaling white matter microstructure findings provide complete view anatomic scaling human brain relevance evolutionary basic clinical neuroscience,0.0
multiple sclerosis focus extracellular artificial vesicles nanoparticles potential therapeutic approaches int j mol sci 2021 aug 18 22 16 8866 doi 103390 ijms22168866abstractmultiple sclerosis ms autoimmune disease central nervous system characterized inflammatory process leading destruction myelin neuronal death neurodegeneration ms lymphocytes cross bloodbrain barrier creating inflammatory demyelinated plaques located primarily white matter ms potential treatments involve various mechanisms action immune cells immunosuppression inhibition passage bloodbrain barrier immunotolerance bionanotechnology represents promising approach improve treatment autoimmune diseases ability affect immune responses use nanotechnology actively investigated development new ms therapies review summarize results studies natural artificial vesicles nanoparticles take look future clinical perspectives application ms therapypmid34445572 doi103390 ijms22168866,1.0
192bp erv fragment insertion first intron porcine tlr6 may act enhancer associated increased expressions tlr6 tlr1 background tolllike receptors tlrs play important roles building innate immune inducing adaptive immune responses associations tlr genes polymorphisms disease susceptibility basis molecular breeding disease resistant animals reported extensively retrotransposon insertion polymorphisms rips new type molecular markers developed recently great potential population genetics quantitative trait locus mapping study bioinformatic prediction combined pcrbased amplification employed screen rips porcine tlr genes population distribution examined one rip impact gene activity phenotype evaluatedresultsfive rips located 3 flank tlr3 5 flank tlr5 intron 1 tlr6 intron 1 tlr7 3 flank tlr8 respectively identified rips detected different breeds uneven distribution among using dual luciferase activity assay 192 bp endogenous retrovirus erv intron 1 tlr6 shown act enhancer increasing activities tlr6 putative promoter two minipromoters furthermore realtime quantitative polymerase chain reaction qpcr analysis revealed significant association p 005 erv insertion increased mrna expression tlr6 neighboring gene tlr1 genes downstream tlr signaling pathway myd88 myeloid differentiation factor 88 rac1 rac family small gtpase 1 tirap tir domain containing adaptor protein tollip toll interacting protein well inflammatory factors il6 interleukin 6 il8 interleukin 8 tnf tumor necrosis factor alpha tissues 30 dayold piglet addition serum il6 tnf concentrations also significantly upregulated erv insertion p 005 conclusionsa total five rips identified five different tlr loci 192 bp erv insertion first intron tlr6 associated higher expression tlr6 tlr1 several genes downstream signaling cascade thus erv insertion may act enhancer affecting regulation tlr signaling pathways can potentially applied breeding disease resistant animals,0.0
recent advances diabetic kidney disease diabetic kidney disease know far clinical presentationdiabetes mellitus leading cause chronic kidney disease ckd usa worldwide estimated 422 million adults living diabetes globally 40 may develop ckd lifetime 1 diabetic kidney disease dkd reflect specific pathological phenotype fact can diagnosed clinically based presence persistent albuminuria sustained reduction estimated glomerular filtration rate egfr patients diabetes 2 dkd usually identified five years diagnosis type 1 diabetes can recognized time diagnosis type 2 diabetes presence proliferative diabetic retinopathy typically correlates ongoing dkd patients albuminuria even though kidney biopsy can confirm diagnosis dkd procedure usually considered alternative diagnosis suspectedalbuminuria recently classified moderate 30 300mg g severe 300mg g nonetheless degree albuminuria associated increased risk ckd progression endstage kidney disease eskd adverse cardiovascular disease outcomes mortality patients diabetes 3 reduced egfr diabetic patients observed absence albuminuria however progression dkd appears slower individuals 3 furthermore combined presence albuminuria lower egfr independently increases risks cardiovascular events mortality individuals diabetes 3 kidney disease improving global outcomes kdigo american diabetes association ada guidelines recommend diabetic patients undergo annual screening checking serum creatininebased egfr urine tests evaluate albuminuria 2 unique challenges dkd compared types kidney diseaseindividuals type 2 diabetes may develop dkd clear diagnosis diabetes established consequence delaying diagnosis appropriate treatment dkd recently witnessed significant progress treatment options slowing dkd real advance reversing dkd date available therapies targeting dkd progression furthermore dkd patients eligible therapies variable side effects hyperkalemia acute kidney injury aki extent dkd indeed safety concerns many newer medications approved patients egfr 30ml min 173m2what known causes dkdhyperaminoacidemia glomerular hyperfiltration hyperperfusion hyperglycemia major metabolic abnormalities affect kidneys associated inflammation eventually fibrosis diabetic patients 4 classic sequence events natural history dkd driven hyperglycemia conjunction hypertension characterized glomerular hyperfiltration progressing albuminuria leading decline kidney function one mechanistic hypothesis suggests decrease distal delivery sodium chloride macula densa results increased proximal tubular reabsorption glucose via sodiumglucose cotransporter 2 leading decrease tubuloglomerular feedback results dilation afferent arteriole increased glomerular perfusion 5 hand increased production angiotensin ii leads vasoconstriction efferent arteriole net effect elevated intraglomerular pressure leading glomerular hyperfiltration 5 additionally systemic hypertension obesity can also contribute glomerular hyperfiltration via glomerular enlargement 4 number factors can play significant role pathogenesis dkd include example oxidative stress activation advanced glycation endproducts age receptors represented multiple cell types kidneys induces production numerous cytokines hyperglycemia causes increased formation age activates protein kinase c resulting decreased production endothelial nitric oxide synthase increased levels endothelin 1 angiopoietins 2 vascular endothelial growth factor furthermore hyperglycemia angiotensin ii age can activate macrophages rich cytokines tumor necrosis factor net effect different pathways leads endothelial instability increased vascular proliferation renal hypertrophy podocyte injury tubular epithelial cell injury increased cytokine production 6 structural changes dkd start thickening glomerular basement membrane followed mesangial matrix expansion foot process effacement 7 segmental mesangiolysis kimmelstielwilson nodules signs dkd progression 8 interstitial fibrosis global sclerosis develop later dkd stageswhat general treatment options dkdintensive glycemic control critical prevention dkd early course disease however number studies shown intensive glucose control may reduce risk ckd progression cardiovascular mortality advanced stages dkd 9 kdigo guidelines recommend target hba1c ranging 65 80 choice exact target guided extent hypoglycemia risk patient 10 glycemic control current guidelines suggest using metformin sodiumglucose cotransporter 2 inhibitors patients dkd gfr 30ml min per 173m2 10 glucagonlike peptide1 receptor agonists can added manage hyperglycemia needed 10 uncontrolled hypertension can worsen dkd increase risk progression eskd kdigo guidelines recommend using angiotensinconverting enzyme inhibitor acei angiotensin receptor blocker arb maintain blood pressure 130 80mmhg patients ckd albuminuria regardless diabetic status prior studies showed aceis arbs offer kidney protection lowering proteinuria slowing rate ckd progression 10 combination regimens aceis arbs recommended due increased risk acute kidney injury hyperkalemiaregarding nonpharmacological therapies kdigo guidelines recommend implementation lifestyle modification among dkd patients including low sodium intake 2g day maintaining protein intake 08g kg day patients dialysis moderateintensity physical activity cumulative duration least 150min per week tolerated 10,0.0
timedependent effect 1 6hexanediol biomolecular condensates 3d chromatin organization background biomolecular condensates implicated multiple cellular processes however global role played condensates 3d chromatin organization remains unclear present 1 6hexanediol 1 6hd available tool globally disrupt condensates yet conditions 1 6hd vary considerably studies may even trigger apoptosisresultsin study first analyzed effects different concentrations treatment durations 1 6hd found shortterm exposure 15 1 6hd dissolved biomolecular condensates whereas longterm exposure caused aberrant aggregation without affecting cell viability based condition drew timeresolved map 3d chromatin organization found shortterm treatment 15 1 6hd resulted reduced longrange interactions strengthened compartmentalization homogenized aa interactions btoa compartment switch tad reorganization whereas longer exposure opposite effects furthermore longrange interactions condensatecomponentenriched regions markedly weakened following 1 6hd treatmentconclusionsin conclusion study finds proper 1 6hd condition provides resource exploring role biomolecular condensates 3d chromatin organization,0.0
extracellular matrix modifier neuroinflammation remyelination multiple sclerosis brain 2021 apr 23awab059 doi 101093 brain awab059 online ahead printabstractremyelination failure contributes axonal loss progression disability multiple sclerosis failed repair process due ongoing toxic neuroinflammation inhibitory lesion microenvironment prevents recruitment differentiation oligodendrocyte progenitor cells myelinforming oligodendrocytes extracellular matrix molecules deposited lesions provide altered microenvironment inhibits oligodendrocyte progenitor cells fuel exacerbates inflammatory responses within lesions review discuss extracellular matrix molecules normally distributed uninjured adult brain specifically basement membranes cerebral vessels perineuronal nets surround soma certain populations neurons interstitial matrix neural cells highlight deposition different extracellular matrix members multiple sclerosis lesions including chondroitin sulphate proteoglycans collagens laminins fibronectin fibrinogen thrombospondin others consider reasons behind changes extracellular matrix components multiple sclerosis lesions mainly due deposition cells reactive astrocytes microglia macrophages next discuss consequences altered extracellular matrix multiple sclerosis lesions besides impairing oligodendrocyte recruitment many extracellular matrix components elevated multiple sclerosis lesions proinflammatory enhance inflammatory processes several mechanisms however molecules thrombospondin1 may counter inflammatory processes laminins appear favour repair overall emphasize crosstalk extracellular matrix immune responses remyelination modulating lesions recovery worsening finally review potential therapeutic approaches target extracellular matrix components reduce detrimental neuroinflammation promote recruitment maturation oligodendrocyte lineage cells enhance remyelinationpmid33889940 doi101093 brain awab059,1.0
23 na imaging worth salt understanding multiple sclerosis proc natl acad sci u s 2021 aug 17 118 33 e2110799118 doi 101073 pnas2110799118no abstractpmid34376559 doi101073 pnas2110799118,0.0
targeting tumor microenvironment bcell lymphoma challenges opportunities abstractbcell lymphoma group hematological malignancies high clinical biological heterogeneity pathogenesis bcell lymphoma involves complex interaction tumor cells tumor microenvironment tme composed stromal cells extracellular matrix although roles tme fully elucidated accumulating evidence implies tme closely relevant origination invasion metastasis bcell lymphoma explorations tme provide distinctive insights cancer therapy epitomize recent advances tme bcell lymphoma discuss function tumor progression immune escape addition potential clinical value targeting tme bcell lymphoma highlighted expected pave way novel therapeutic strategies,0.0
urinary small extracellular vesicles derived ccl21 mrna biomarker linked pathogenesis diabetic nephropathy background diabetic nephropathy dn leading cause renal failure whereas effective early diagnostic biomarkers still lackingmethodsfourteen cytokines chemokines mrna detected urinary extracellular vesicles evs screening cohort including 4 healthy controls hc 4 diabetes mellitus dm 4 biopsyproven dn patients validated another 16 hc 15 dm 28 dn patients correlation analysis performed candidate biomarkers clinic parameters well kidney histological changes findings also confirmed dn rat model single injection stzresultsthe number small evs secreted urine increased dn patients compared dm patients healthy controls expression aqp1 marker proximal tubules aqp2 marker distal collecting tubules small evs derived ccl21 mrna increased significantly dn patients correlated level proteinuria egfr interestingly elevated ccl21 mrna urine small evs observed dn patients normal renal function discriminate early dn patients dm efficiently compared egfr proteinuria ccl21 also showed accurate diagnostic ability distinguishing incipient overt dn histologically ccl21 mrna expression increased progressively deterioration tubulointerstitial inflammation showed highest level nodular sclerosis group class iii dn patients remarkable infiltration cd3 positive t cells including cd4 cd8 positive t cell population observed dn patients highccl21 expression besides accumulation cd3 positive t cells correlated level urinary small evs derived ccl21 colocalized ccl21 tubulointerstitium dn patients finally correlation ccl21 expression renal cortex urinary small evs confirmed stzinduced dn rat modelconclusionsurinary small evs derived ccl21 mrna may serve early biomarker identifying dn linked pathogenesis ccl21 mrna mediated t cell infiltration may constitute key mechanism chronic inflammation dn,0.0
lower blood malondialdehyde associated past pesticide exposure findings gulf war illness healthy controls background malondialdehyde mda candidate general marker oxidative stress os sought assess relation mda gulf war illness gwi variety exposuresmethodsthis observational study involving subjects southern california recruited october 2011 may 2014 mda assessed 81 participants 41 gwicases 40 controls general gulfspecific exposures elicited mda casecontrol comparison restricted 40 matched pairs potential association mda exposures assessed using regression analyses gulfspecific exposures incorporated casespecific modelresultsplasma mda significantly lower gwicases controls composite pesticide fuelsolvent exposures negatively predicted mda total sample well analyses included either gwicases controls selfreported exposure organophosphate op nerve gas strong predictor lower mda level veterans gwiconclusionpast pesticide exposures predicted lower mda veterans gwi healthy controls,0.0
latitude gradient multiple sclerosis prevalence established early lifecourse brain 2021 mar 11awab104 doi 101093 brain awab104 online ahead printabstractthe strongest epidemiological clue environment population level significant impact risk developing multiple sclerosis ms wellestablished many instances increasing latitudinal gradient prevalence incidence mortality globally prevalence increasing 10fold equator 60 degrees north south drivers gradient thought environmental latitude seen proxy ultraviolet radiation thus vitamin d production however factors may also play role however several important questions remain unanswered particularly life course gradient established lifetime migration mitigate exacerbate previously reported latitude gradients location diagnosis factors sex ms disease phenotype influence timing significance gradient utilising life time residence calendars collected part new zealand national ms prevalence study constructed lifetime latitudinal gradients ms birth prevalence day 2006 taking account migration internally externally analysed sex ms clinical course phenotype 2127 2917 people living nz prevalence day 7 march 2006 ms completed life course questionnaire 1587 born nz cohorts sub cohorts representative overall ms population nz prevalence day found prevalence gradient present birth fact stronger census day slope gradient persisted age 12 gradually declining found internal external migration nz little effect gradient except decrease significance gradient somewhat finally found reported previously lifetime prevalence gradients largely driven females relapse onset ms findings confirm first time importance early life environmental exposures risk ms indicating strongly exposures early utero birth drive latitudinal gradient consequently prevention studies focussed high risk individuals populations earliest possible time points especially appropriate femalespmid33704407 doi101093 brain awab104,0.0
decoding neural activity sulcal white matter areas brain accurately predict individual finger movement tactile stimuli human hand front neurosci 2021 aug 17 15699631 doi 103389 fnins2021699631 ecollection 2021abstractmillions people worldwide suffer motor sensory impairment due stroke spinal cord injury multiple sclerosis traumatic brain injury diabetes motor neuron diseases als amyotrophic lateral sclerosis braincomputer interface bci links brain directly computer offers new way study brain potentially restore impairments patients living debilitating conditions one challenges currently facing bci technology however minimize surgical risk maintaining efficacy minimally invasive techniques stereoelectroencephalography seeg become widely used clinical applications epilepsy patients since can lead fewer complications seeg depth electrodes also give access sulcal white matter areas brain widely studied braincomputer interfaces show first demonstration decoding sulcal subcortical activity related movement tactile sensation human hand furthermore compared decoding performance seegbased depth recordings versus obtained electrocorticography electrodes ecog placed gyri initial poor decoding performance observation neural modulation patterns varied amplitude trialtotrial transient significantly shorter sustained finger movements studied led development feature selection method based repeatability metric using temporal correlation algorithm based temporal correlation developed isolate features consistently repeated required accurate decoding possessed information content related movement touchrelated stimuli subsequently used features along deep learning methods automatically classify various motor sensory events individual fingers high accuracy repeating features found sulcal gyral white matter areas predominantly phasic phasictonic across wide frequency range hd high density ecog seeg recordings findings motivated use long shortterm memory lstm recurrent neural networks rnns wellsuited handling transient input features combining temporal correlationbased feature selection lstm yielded decoding accuracies 9204 151 hand movements 9169 049 individual finger movements 8349 072 focal tactile stimuli individual finger pads using relatively small number seeg electrodes findings may lead new class minimally invasive braincomputer interface systems future increasing applicability wide variety conditionspmid34483823 pmcpmc8415782 doi103389 fnins2021699631,0.0
process evaluation mind back trial examining psychologically informed physical treatments chronic low back pain background chronic conditions back pain use interventions address physical social psychological aspects within biopsychosocial framework encouraged however applying holistic multimodal approach physical therapy practice ie chiropractic physiotherapy challenging explore problem delivering biopsychosocially informed package care physical therapy practice recent randomised control trial rct called mind back conducted evaluate effectiveness combined physical internetdelivered psychological intervention psychologically informed physical treatments compared standard treatment improving disability selfefficacy people chronic lbp results trial indicated difference two intervention groups although highquality rcts considered gold standard effectiveness interventions qualitative research methods embedded within process evaluation framework also used reveal issues important information help explain clinical trial results field digital health interventions research therefore within process evaluation framework aim explore participants experiences interventions received throughout mind back trial led null resultmethodsinline recommendations process evaluation study used indepth interviews qualitative thematic analysis participants arms trial 56 months study completion semistructured telephone interviews conducted twentyfive participants explore experiences taking part mind back trial interviews conducted november 2017 transcribed verbatim data analysed thematicallyresultstwo main themes identified 1 personalised support therapeutic alliance important 2 moodgym lacked relevant personalised tailored supportconclusionit important deliver tailored digital health supports personalised fosters therapeutic alliance,0.0
corrigendum age diagnosis influence use health services multiple sclerosis multiple sclerosis related disorders 46 2020 102555 background clinical studies suggest disease course multiple sclerosis ms differs according age onset however studies crosssectional modest sample sizes populationbased administrative data provide alternative longterm perspective disease progression document association age diagnosis progression ms objective study association age diagnosis use health services ms methods data 1426 subjects ms extracted qubec birth cohort immunity health includes 400 611 individuals born qubec 1970 1974 followed 2014 using administrative databases subjects 3 hospital physician claims ms followup classified ms using algorithm validated previously four indicators health services use ms considered number visits neurologist number visits general practitioner gp number visits emergency room number days hospitalization generalized additive models quasipoisson distribution used estimate association age diagnosis rates health services models adjusted duration followup proportion women proportion individuals materially socially disadvantaged results subjects 76 women 29 21 29 years old ms diagnosis subjects diagnosed ms age 29 years higher rate visits neurologist higher rate hospitalization lower rate visits gp first year following ms diagnosis compared diagnosed age 29 years later many differences observed subjects ms diagnosis 29 years ms diagnosis least 29 years periods followup indicators health services conclusion although observed changes rates visits neurologist gp two diagnostic age groups conclude age diagnosis influences rate health services ms use health services allowed us describe association age diagnosis progression ms population level,0.0
calcium permeableampa receptors excitotoxicity neurological disorders front neural circuits 2021 aug 17 15711564 doi 103389 fncir2021711564 ecollection 2021abstractexcitotoxicity one primary mechanisms cell loss variety diseases central peripheral nervous systems previously established signaling pathways excitotoxicity depend excessive release glutamate axon terminals overactivation nmda receptors nmdars ca2+ influxtriggered excitotoxicity ca2+permeable cp ampa receptors ampars detected multiple disease models review acute brain insults eg brain trauma spinal cord injury ischemia chronic neurological disorders including epilepsy seizures huntingtons disease hd parkinsons disease pd alzheimers disease ad amyotrophic lateral sclerosis als chronic pain glaucoma discussed regarding cpamparmediated excitotoxicity considering low expression absence cpampars cells specific manipulation cpampars might plausible strategy delay onset progression pathological alterations fewer side effects blocking nmdarspmid34483848 pmcpmc8416103 doi103389 fncir2021711564,0.0
immunopeptidomics toolkit library iptk pythonbased modular toolbox analyzing immunopeptidomics data background human leukocyte antigen hla proteins play fundamental role adaptive immune system present peptides t cells massspectrometrybased immunopeptidomics promising powerful tool characterizing immunopeptidomic landscape hla proteins peptides presented hla proteins despite growing interest technology recent rise immunopeptidomicsspecific identification pipelines still gap dataanalysis software tools specialized analyzing visualizing immunopeptidomics dataresultswe present iptk library opensource pythonbased library analyzing visualizing comparing integrating different omics layers identified peptides indepth characterization immunopeptidome using different datasets illustrate ability library enrich result identified peptidomes also demonstrate utility library developing software tools developing easytouse dashboard can used interactive analysis resultsconclusioniptk provides modular extendable framework analyzing integrating immunopeptidomes different omics layers library deployed pypi https pypiorg project iptkl bioconda https anacondaorg bioconda iptkl source code library dashboard along online tutorials available https githubcom ikmb iptoolkit,0.0
deep grey matter injury multiple sclerosis naims consensus statement brain 2021 mar 23awab132 doi 101093 brain awab132 online ahead printabstractalthough multiple sclerosis ms traditionally considered white matter disease extensive research documents presence importance gray matter injury including cortical deep regions deep gray matter dgm exhibits broad range pathology uniquely suited study mechanisms clinical relevance tissue injury ms using magnetic resonance techniques dgm injury associated clinical cognitive disability recently mri characterization dgm properties thalamic volume tested potential clinical trial endpoints associated neurodegenerative aspects ms given emerging area interest potential clinical trial relevance north american imaging ms naims cooperative held workshop reached consensus imaging topics related dgm herein review current knowledge regarding dgm injury ms imaging perspective including insights histopathology image acquisition postprocessing dgm discuss clinical relevance dgm injury specific regions interest within dgm highlight unanswered questions propose future directions aim focusing research priorities towards better methods analysis interpretation resultspmid33757115 doi101093 brain awab132,0.0
orexinergic system neurodegenerative diseases front aging neurosci 2021 aug 17 13713201 doi 103389 fnagi2021713201 ecollection 2021abstractorexinergic system consisting orexins orexin receptors plays essential role regulating sleepwake states whereas sleep disruption common symptom number neurodegenerative diseases emerging evidence reveals orexinergic system disturbed various neurodegenerative diseases including alzheimers disease ad parkinsons disease pd huntingtons disease hd multiple sclerosis ms whereas dysregulation orexins orexin receptors contributes pathogenesis diseases review summarized advanced knowledge orexinergic system role sleep reviewed dysregulation orexinergic system role pathogenesis ad pd hd ms moreover therapeutic potential targeting orexinergic system treatment diseases discussedpmid34483883 pmcpmc8416170 doi103389 fnagi2021713201,0.0
biopsychosocial implications living multiple sclerosis qualitative study using interpretative phenomenological analysis bmj open 2021 aug 17 11 8 e049041 doi 101136 bmjopen2021049041abstractbackground multiple sclerosis ms estimated affect 28 million people worldwide increasing prevalence world regions walton et al cure ms medication lifestyle modifications can slow disease progression enhance patients quality life biopsychosocial model health recognises important interactions among biological psychological social factors illness including relating illness management contribute experience diagnosed msobjective qualitative idiographic study aimed explore lived experiences patients united arab emirates uae diagnosed smethods semistructured interviews conducted purposive sample eight patients ms ranging age 25 56 years participants residing uae time data collection interpretative phenomenological analysis used analyse dataresults three superordinate themes identified patients candid accounts lives ms highlighting issues illness management acceptance gratitude adaptive coping themes broadly illustrate biological psychological social aspects patients ms experiencesconclusion study emphasised importance adopting biopsychosocial model treat manage ms additionally highlights need routine assessment early multidimensional approach multidisciplinary team efforts improve patients quality lifepmid34404710 doi101136 bmjopen2021049041,0.0
exploring csf neurofilament light biomarker ms clinical practice retrospective registrybased study abstractbackgroundneurofilament light nfl increasingly recognized prognostic therapeutic decisionsobjectiveto validate utility cerebrospinal fluid nfl cnfl biomarker clinical practice relapsingremitting multiple sclerosis rrms methodsrrms patients n757 cnfl analyzed part diagnostic workup single academic multiple sclerosis ms center 20012018 retrospectively identified cnfl concentrations determined two different immunoassays ratio means used normalizationresultsrrms relapse 44 times higher median cnfl concentration 1134 interquartile range iqr 4992744 ng l without relapse 264 125537 ng l p0001 patients gadoliniumenhancing lesions 33 times higher median nfl 1414 60683210 ng l without 426 iqr 221851 ng l p0001 sensitivity specificity cnfl detect disease activity 75 985 respectively high cnfl ms onset predicted progression expanded disability status scale edss 3 p0001 hazard ratios hr 189 95 ci144265 conversion secondary progressive ms spms p0001 hr25 95 ci1442 conclusionscnfl robust reliable biomarker disease activity treatment response prediction disability conversion rrms spms data suggest cnfl included assessment patients msonset,0.0
reinforcing evidence oligoclonal bands prognostic factor patients multiple sclerosis abstractthe prognostic value oligoclonal bands cerebrospinal fluid multiple sclerosis ms patients controversial several studies demonstrated worse disease course ocb positive patients others reproduce findings evaluated prognostic significance ocb retrospectively based clinical records ocb status upon diagnosis severity outcomes including ms severity score progression index regional involvement magnetic resonance imaging ocb positive patients higher median msss pi greater proportion spinal cord involvement findings provide evidence prognostic importance ocb ms patients,0.0
shear wave elastography optic neuritis diagnostic accuracy optic nerve adjacent fat tissue values j ultrason 2021 aug 16 21 86 e194e199 doi 1015557 jou20210031 epub 2021 sep 9abstractintroduction study attempt determine diagnostic performance shear wave elastography optic nerve adjacent fat tissue patients optic neuritis methods study included patient group consisting 72 eyes 36 patients diagnosed unilateral optic neuritis agematched control group 36 eyes 18 healthy subjects patient group consisted 25 multiple sclerosis patients 11 recurrent isolated optic neuritis patients mean shear wave elastography values optic nerves intraorbital fat tissue adjacent optic nerves recorded using m s kpa units roc curve analysis performed diagnostic accuracy shear wave elastography values determined results mean shear wave elastography values optic nerves neuritis 249 041 m s 1756 442 kpa significantly higher values contralateral normal optic nerves 171 032 m s 902 234 kpa p 0006 p 0004 respectively optic neuritis group mean shear wave elastography values intraorbital fat tissue adjacent optic nerves neuritis 187 032 m s 965 112 kpa significantly higher values contralateral normal side 147 027 m s 678 114 kpa p 0025 p 0022 respectively optic neuritis group roc curve analysis showed high diagnostic accuracy determining optic neuritis shear wave elastography values optic nerves auc 0955 95 ci 09330978 m s auc 0967 95 ci 09400985 kpa conclusions shear wave elastography may important alternative diagnostic tool diagnosis optic neuritispmid34540272 pmcpmc8439124 doi1015557 jou20210031,0.0
interests concerns regarding medical marijuana among chronic pain patients ohio online survey background since legalization medical marijuana mmj ohio 2018 many chronic pain cp patients become interested alternative adjunct prescription opioids created need pain management specialists learn potential indication mmj also detailed knowledge patient attitudes willingness comply providers recommendations regarding safe use pain medications purpose surveyed cp patients region severely affected opioid crisis order provide better education formulate treatment plans develop clinical policiesmethodswe designed administered medical marijuana interest questionnaire mmiq online patients western reserve hospital center pain medicine cpm diagnosis cp yet using mmj questions addressed demographic clinical characteristics willingness consider mmj compliance treatment plans concerns carried statistical analysis including pearson chisquare spearmans rho kendalls tau tests measure associations variables identify factors may influence willingness use mmjresultsafter sending 1047 email invitations complete mmiq 242 231 completed questionnaires returned average age range respondents 5160 years 171 707 female 147 607 current opioid users 204 843 respondents willing consider using mmj given access entire questionnaire 138 676 reported wanting use less opioids starting mmj 191 936 amenable following pain specialists recommendations using mmj concurrently opioids greatest concern 05 scale affordability 298 statistically significant negative correlation older age preference inhaled forms p 0023 conclusionthe mmiq successful eliciting important data regarding patients attitudes mmj opioid titration potential compliance study limited administered online rather inperson skewed demographic makeup sample mmiq can used study similar populations adapted patients already using mmj similar surveys mmjexperienced patients combined chart reviews study success products pain control opioid substitution,0.0
perturbation practice multiple sclerosis assessing generalization support surface translations tetherrelease tasks abstractobjectiveto determine whether improvements protective stepping experienced repeated support surface translations generalize different balance challenge people multiple sclerosis pwms backgroundms affects almost 1 million people united states impairs balance mobility perturbation practice can improve aspects protective stepping pwms whether improvements generalize unknownmethodsfourteen pwms completed two visits 24hrs apart balance tasks included tetherrelease trials support surface translations treadmill eliciting backward protective stepping margin stability step length step latency calculated generalization assessed via multilevel mediation models mlmm bootstrapping produce percentile bias corrected confidence intervalsresultsthere mediated effects margin stability step latency however mediation observed step length indicating participants increased step length throughout treadmill trials generalized tetherrelease trialsdiscussionmlmm may useful evaluating generalization motor training novel balance situations particularly small sample sizes using analyses observed pwms generalized improvements step length suggesting aspects protective step training may translate improvements reactive balance tasks pwms,0.0
covid19 severity outcome multiple sclerosis results national registrybased matched cohort study abstractbackgroundrisk factors associated coronavirus disease 2019 covid19 severity patients multiple sclerosis ms described recent improvements supportive care measures increased testing capacity may modify risk severe covid19 outcome ms patients retrospective study evaluates severity outcome covid19 ms characterizes temporal trends course pandemic united statesmethodswe conducted comparative cohort study using deidentified electronic health record ehr claimsbased data ms patients diagnosed covid19 february 2 2020 october 13 2020 matched 12 control group using propensity score analysis primary outcome composite intensive care unit icu admission mechanical ventilation deathresultsa total 2 529 patients 843 ms 1 686 matched controls included nonambulatory preexisting comorbidities independent risk factors covid19 severity risk severe composite outcome lower late cohorts compared early cohortsconclusionsthe majority ms patients actively treated diseasemodifying therapy dmt mild disease observed trend toward reduction severity risk recent months suggests improvement covid19 outcome,0.0
neurofilament light chain biomarker diagnosis multiple sclerosis excli j 2021 aug 16 2013081325 doi 1017179 excli20213973 ecollection 2021abstractthe treatments multiple sclerosis ms improved past 25 years now main question physicians deciding receive treatment long switch options decisions typically based treatment tolerance reasonable expectation longterm efficacy significant unmet need lack accurate laboratory measurements diagnosis monitoring treatment response including deterioration disease progression validated biomarkers ms practice physicians employ two biomarkers discovered fifty years ago ms diagnosis often combination mri scans biomarkers intrathecal igg oligoclonal bands csf cerebrospinal fluid neurofilament light chain nfl relatively new biomarker ms diagnosis follow neurofilaments neuronspecific cytoskeleton proteins can measured various body compartments nfl new biomarker ms can measured serum samples still needs study specify laboratory cutoff values clinical practice present review discuss evidence nfl reliable biomarker early detection management ms moreover highlight correlation mri nfl ask whether can combinedpmid34602928 pmcpmc8481790 doi1017179 excli20213973,0.0
association selected multiple sclerosis symptoms disability quality life large danish selfreport survey background people multiple sclerosis ms experience wide range unpredictable variable symptoms symptomatology ms previously reported large sample registry studies however symptoms may underreported registries based clinicianreported outcomes symptoms associated quality life qol often addressedthe aim study comprehensively evaluate frequency selected ms related symptoms associations disability qol large selfreport studymethodswe conducted crosssectional questionnaire survey among patients danish multiple sclerosis center copenhagen university hospital denmark questionnaire included information clinical sociodemographic characteristics descriptors qol disability well prevalence severity following ms symptoms impaired ambulation spasticity chronic pain fatigue bowel bladder dysfunction sleep disturbancesresultsquestionnaires returned 2244 3606 62 participants without ms diagnosis incomplete questionnaires excluded n 235 total 2009 questionnaires included analysis mean age 494 years mean disease duration 117 years 69 women frequently reported symptoms bowel bladder dysfunction 74 fatigue 66 sleep disturbances 59 spasticity 51 impaired ambulation 38 exception fatigue sleep disturbances symptoms increased severity higher disability level invisible symptoms also referred hidden symptoms fatigue pain sleep disturbances strongest associations overall qolconclusionwe found invisible symptoms highly prevalent even mild disability levels fatigue pain sleep disturbances strongest associations overall qol frequently reported study compared previous registrybased studies symptoms may underreported registries based clinician reported outcomes emphasizes importance including standardized patient reported outcomes nationwide registries better understand impact symptom burden ms,0.0
quality life children adolescents multiple sclerosisa literature review quantitative evidence int j environ res public health 2021 aug 16 18 16 8645 doi 103390 ijerph18168645abstractbackground multiple sclerosis ms chronic disease central nervous system also develops patients 18 years age disease negatively affects quality life qol children adolescents conducted literature review aim review identify qol pediatric patients ms assess factors determining qolmethods analyzed studies published 2000 2020 pubmed scopus science direct web science ebsco databasesresults 17 studies included review common tool assessing qol generic module pedsql range mean median global score qol 538817 worst qol dominantly reported school emotional spheres contrary diseases least determined area qol social physical dimension particular disability fatigue important predictors qolconclusions ms negatively affects school emotional spheres particular important pay greater attention spheres life ms patients review studies pay insufficient attention analysis positive factors impact qol ms patients research integrate phenomena use mstargeted tools future research pediatric ms population also appropriatepmid34444393 doi103390 ijerph18168645,0.0
acute arthritis right temporomandibular joint due lyme disease case report literature review background lyme disease frequent tickborne infectious disease europe often presents wide variety symptoms reason affection temporomandibular joint tmj caused lyme disease ld can misdiagnosed common temporomandibular disorder tmd case presentationthe purpose case report 25yearold woman presenting departments orthodontics oral maxillofacial surgery extensive symptoms temporomandibular disorder illustrate delayed diagnosis lyme disease made extensive therapy temporomandibular joint specialist literature reports cases patients suffering lyme disease tmj manifestationsconclusionthis case report relevant literature review aim emphasize importance accurate request medical history differential diagnosis acute tmj arthritis arthralgia early interdisciplinary diagnosis lyme disease early antibiotic therapy essential avoid misdiagnosis unnecessary sometimes invasive therapies,0.0
influence selfperception manipulative dexterity adults multiple sclerosis occup ther int 2021 aug 16 20215583063 doi 101155 2021 5583063 ecollection 2021abstractbackground multiple sclerosis disorder causes loss functionality affecting persons ability perform activities daily living interpersonal interactions relationship dressing selfcare bathing well negative impact work leisure activitiesaims study examined relationship correlational associations predictive selfperceived quality life performance manipulative dexterity also study sought measure predictors dexterity study design crosssectional study two associations ms within community madrid spain methods procedures final sample 30 people multiple sclerosis outcome measures used abilhand questionnaire purdue pegboard test nine hole peg test box block testresults significant correlations found dexterity selfperception tests however correlations found perceived dexterity quality life p 0001 scores abilhand questionnaire measures perception skills daily living predicted 60 variance dexterity testsconclusions results study suggest interventions improving manipulative dexterity people multiple sclerosis address persons perception improving manipulative dexterity perceived quality life factors may influence manipulative dexteritypmid34483781 pmcpmc8384504 doi101155 2021 5583063,0.0
widespread disruptions white matter familial multiple sclerosis dti noddi study front neurol 2021 aug 16 12678245 doi 103389 fneur2021678245 ecollection 2021abstractdiffusion tensor imaging dti noninvasive quantitative mri technique measures white matter wm integrity many brain dimensions heritable including white matter integrity measured dti family studies valuable provide insights interactive effects nonenvironmental factors multiple sclerosis ms examine contribution familial factors diffusion signals across wm microstructure performed dti calculated neurite orientation dispersion plus density imaging noddi diffusion parameters two patient groups comprising familial sporadic forms multiple sclerosis unaffected relatives divided 111 subjects 49 men 62 women age range 1960 three groups conforming ms history familial ms group included 30 participants patients n 16 healthy relatives n 14 sporadic group included 41 participants patients n 10 healthy relatives n 31 forty agematched subjects history ms families defined control group study white matter integrity two methods employed one calculating mean dti fa md parameters 18 tracts using tracts constrained underlying anatomy tracula whole brain voxelbased analysis using tractbased spatial statistics tbss ndi odi parameters derived noddi dti parameters voxelbased analysis showed considerable changes fa md ndi odi familial group compared control group reflecting widespread impairment white matter group analysis 18 tracts tracula revealed increased md fa reduction tracts left right ilf unc slft forceps major minor familial ms patients vs control group significant differences patient groups found consequential changes healthy relatives patient groups voxelbased tract analyses considering multifactorial etiology ms familial studies great importance clarify effects certain predisposing factors demyelinating brain pathologypmid34484098 pmcpmc8415561 doi103389 fneur2021678245,1.0
multiple sclerosis associated increased risk severe covid19 nationwide retrospective crosssectional study germany background since coronavirus disease 2019 covid19 risen several risk factors identified predicting worse outcome speculated patients multiple sclerosis ms increased risk severe course covid19 due suspected higher vulnerability therefore aimed analyze impact comorbid ms outcome patients covid19 germanymethodswe conducted retrospective crosssectional study using administrative database hospitalized patients diagnosed pcrconfirmed covid19 n 157 524 germany 2020 cohort stratified according presence n 551 absence n 156 973 comorbid ms including discrimination ms subtypes primary outcome measures admission intensive care unit icu use invasive noninvasive ventilation inhospital mortality differences investigated using rates odds ratios estimates pooled overall estimates sexstratified estimates agegroup stratified estimates ms subtype stratified estimates calculated outcomes randomeffects modelresultsamong 157 524 patients hospitalized covid19 551 concurrent ms diagnosis 03 overall univariate analysis showed lower rates icu admission 171 versus 227 p 0001 lower use ventilation 98 versus 145 p 0001 lower inhospital mortality 111 versus 193 p 0001 among covid19 patients comorbid ms finding stable across subgroup analysis sex ms subtype attenuated agestratification confirming equal odds inhospital mortality covid19 patients without ms log 009 95 ci 040 059 conclusionsalthough might differences risk within ms patients population largescale nationwide analysis found evidence worse outcome covid19 patients comorbid ms compared nonms individuals,0.0
helicobacter pylori infection bacteria pancreatic cancer autoimmune pancreatitis world j gastrointest oncol 2021 aug 15 13 8 835844 doi 104251 wjgov13i8835abstracthelicobacter pylori h pylori infectious agent influencing much 50 worlds population causative agent several diseases especially gastric duodenal peptic ulcer gastric adenocarcinoma mucosaassociated lymphoid tissue lymphoma stomach number extragastric manifestations also associated h pylori infection include neurological disorders alzheimers disease demyelinating multiple sclerosis parkinsons disease also evidence relationship h pylori infection dermatological diseases psoriasis rosacea well connection infection openangle glaucoma generally little known relationship h pylori infection diseases pancreas evidence h pylori potential role development pancreatic diseases concerns pancreatic adenocarcinoma autoimmune forms chronic pancreatitis data albeit fully consistent indicating modestly increased pancreatic cancer risk h pyloripositive patients pathogenetic mechanism increase yet fully elucidated several theories proposed reduction antral dcells h pyloripositive patients causes suppression somatostatin secretion turn stimulates increased secretin secretion stimulates pancreatic growth thus increases risk carcinogenesis alternatively h pylori part microbiome dysbiosis socalled oncobiome proven associated pancreatic adenocarcinoma development via promotion cellular proliferation role h pylori inflammation characteristic autoimmune pancreatitis seems explained mechanism molecular mimicry among several proteins mostly enzymes h pylori pancreatic tissue patients autoimmune pancreatitis often show positivity antibodies h pylori proteins h pylori part microbiome dysbiosis also viewed potential trigger autoimmune inflammation pancreas precisely relationships associated equivocal conclusions constitute center attention among pancreatologists immunologists pathologists order obtain clear valid results studies sufficiently large cohorts patients needed topic sufficiently significant draw interest clinicians inspire systematic research nextgeneration sequencing play important role investigating microbiome potential diagnostic prognostic biomarker pancreatic cancerpmid34457189 pmcpmc8371525 doi104251 wjgov13i8835,1.0
clinical effects associated fiveyear retinal nerve fiber layer thinning multiple sclerosis j neurol sci 2021 jun 23 427117552 doi 101016 jjns2021117552 online ahead printabstractbackground neurodegenerative changes multiple sclerosis ms associated longterm disability progression dp optical coherence tomography oct measures may used monitor dpobjective determine significant effects driving changes octbased peripapillary retinal nerve fiber layer prnfl heterogeneous group ms patientsmethods total 144 ms patients 109 relapsingremitting ms 35 progressive ms pms mean age baseline 476 565 years old respectively underwent clinical oct examination 5year followup oct exams reviewed using oscarib criteria 5year dp determined based expanded disability status scale edss changes ms clinical trial criteria data regarding previous history ms optic neuritis mson use disease modifying treatment dmt derived inperson interview review electronic medical records mixed modeltype repeated measure analysis determined effects driving prnfl change analysis utilized eyes separatelyresults average 53years followup ms population demonstrated significant prnfl thinning f 16108 p 0001 prnfl thinning greater due progressive ms subtype f 5102 p 0025 greater age baseline f 4554 p 0034 occurrence dp f 6583 p 0011 previous history mson f 7053 p 0008 use highly potent dmt natalizumab versus firstline injectable treatments versus dmt significantly reduced prnfl thinning f 8367 p 0004 followup lastly occurrence dp pms patients older 50 years old associated greater prnfl thinning f 6667 p 0013 conclusion longitudinal prnfl changes modified age disease subtype disabiltiy progression history mson dmt use interactionspmid34175775 doi101016 jjns2021117552,0.0
utilizing structure based drug design metabolic soft spot identification optimize vitro potency vivo pharmacokinetic properties leading discovery novel reversible bruton#39 s tyrosine kinase inhibitors bioorg med chem 2021 jun 15 44116275 doi 101016 jbmc2021116275 online ahead printabstractbrutons tyrosine kinase btk essential node bcr signaling b cells clinically validated play critical role bcell lymphomas various autoimmune diseases multiple sclerosis ms pemphigus rheumatoid arthritis ra although nonselective irreversible btk inhibitors approved oncology due emergence drug resistance bcell lymphoma associated covalent inhibitor unmet medical need identify reversible selective potent btk inhibitor viable therapeutics patients herein describe identification hits subsequence optimization improve physicochemical properties potency kinome selectivity leading discovery novel class btk inhibitors utilizing met id structure base design inhibitors synthesized increased vivo metabolic stability oral exposure rodents suitable advancing lead optimizationpmid34314938 doi101016 jbmc2021116275,1.0
selfreported occupational functioning persons relapsingremitting multiple sclerosis personality matter j neurol sci 2021 jun 29 427117561 doi 101016 jjns2021117561 online ahead printabstractbackground multiple sclerosis ms poses major threat sustainable employability identifying conditions factors promote work participation great importance objective explore contribution personality traits explaining occupational functioning msmethods 241 participants relapsingremitting ms 78 female median age 420 years median edss 20 60 healthy controls 70 female median age 450 years underwent neuropsychological neurological examinations completed questionnaires multivariate logistic linear regression analyses conducted examine relations personality traits selfreported occupational functioning accounting known correlatesresults personality traits associated selfreported occupational functioning correcting known correlates higher impact fatigue b 005 p 005 b 004 p 009 depression b 022 p 008 b 021 p 01 associated paid job r2 013 considering reduce work hours r2 012 higher impact fatigue b 005 p 008 046 p 001 036 p 001 associated absenteeism work r2 015 presenteeism r2 035 lower work ability r2 025 higher impact fatigue 046 p 001 anxiety 025 p 001 associated work difficulties r2 054 conclusion personality traits explain additional variance selfreported occupational functioning persons relapsingremitting ms mild disability impact fatigue main consistent correlate occupational functioning often combined depression anxiety total explained variance models limited emphasizing need additionally examine contextual factors considering occupational challenges mspmid34216973 doi101016 jjns2021117561,0.0
bistable multiport valve enables microformulators creating microclinical analyzers reveal aberrant glutamate metabolism astrocytes derived tuberous sclerosis patient sens actuators b chem 2021 aug 15 341129972 doi 101016 jsnb2021129972 epub 2021 apr 20abstractthere need valves pumps operate microscale precision accuracy versatile application easily fabricated end developed new rotary planar multiport valve faithfully select solutions contamination 522 006 ppb rotary planar peristaltic pump precisely control fluid delivery flow rate 24 17 890 77 l min valve pump implemented planar format amenable singlelayer soft lithographic fabrication planar microfluidics actuated rotary motor controlled remotely custom software together two devices constitute innovative microformulator used prepare precise highfidelity mixtures five solutions deviation prescribed mixture 002 002 system weighed less kilogram occupied around 500 cm3 generated pressures 255 47 kpa microformulator combined electrochemical sensor creating microclinical analyzer ca detecting glutamate real time using chamber ca inline bioreactor compared glutamate homeostasis human astrocytes differentiated humaninduced pluripotent stem cells hipscs control subject cc3 tuberous sclerosis complex tsc patient carrying pathogenic tsc2 mutation challenged glutamate tsc astrocytes took less glutamate control cells data validate analytical power ca utility microformulator leveraging assess diseaserelated alterations cellular homeostasispmid34092923 pmcpmc8174775 doi101016 jsnb2021129972,0.0
seasonal fluctuations serum levels vitamin d japanese patients multiple sclerosis j neuroimmunol 2021 jun 2 357577624 doi 101016 jjneuroim2021577624 online ahead printabstractwe explored presence seasonal fluctuations serum vitamin d levels potential relationship vitamin d levels disease severity prognosis patients multiple sclerosis ms northern japan serum levels 25 oh d spring significantly lower summer autumn whereas differences 1 25 oh 2d levels demonstrated among four seasons seasonal fluctuations 25 oh d demonstrated patients edss 35 edss40 negative correlations 25 oh d edss msss found season seasonal fluctuations 25 oh d levels may affected physical disabilitiespmid34098399 doi101016 jjneuroim2021577624,0.0
serum neurofilament light sensitive biomarker reflects grey matter volume japanese patients multiple sclerosis j neurol sci 2021 jun 2 427117528 doi 101016 jjns2021117528 online ahead printabstractobjective evaluate degree neuroaxonal injury japanese multiple sclerosis ms patients using serum neurofilament light snfl investigate relationship snfl degree brain volumemethods snfl levels 82 consecutive japanese ms patients remission crosssectionally evaluated using single molecule array assay within sample crosssectional volumetric brain mri data evaluated 80 patients longitudinal data evaluated 63 patientsresults ms patients female male 61 21 including relapsingremitting ms 82 secondary progressive ms 17 primary progressive ms 1 studied mean age patients 412 87 years 77 ms patients 94 treated diseasemodifying therapy dmt median snfl level 7985 iqr 5959109 snfl levels significantly correlated grey matter volume age standard least squares regression model revealed approximately 57 variation grey matter volume explained regression equation using three explanatory variables snfl concentration age sex moreover snfl level multiplied disease duration significantly correlated expanded disability status scale edss scores whole grey matter volumesconclusion although neuroaxonal injury appeared mild japanese ms patients snfl levels significantly reflected grey matter volume moreover multiplied disease duration snfl can reflect disability brain volumepmid34098375 doi101016 jjns2021117528,0.0
burden cost comorbidities patients neuromyelitis optica spectrum disorder j neurol sci 2021 jun 3 427117530 doi 101016 jjns2021117530 online ahead printabstractbackground neuromyelitis optica spectrum disorder nmosd associated various comorbidities including nonautoimmune autoimmune conditions burden cost illness nmosd unclear particularly context comorbiditiesmethods claims data ibm marketscan commercial medicare supplemental databases 2014 2018 analyzed patients nmosd specified inpatient outpatient claims nmosd diagnosis specific nmosd symptoms claims subsequent claims multiple sclerosis ms use ms diseasemodifying therapy dmt continuous enrollment 6 months 1 year first claim index date required study inclusion total costs stratified comorbidities within 12 months postindex date calculated per patient compared 15 matched nonnmosd controlsresults total 162 patients nmosd 810 nonnmosd controls evaluated significantly higher proportion nmosd patients comorbidities nonnmosd controls 667 vs 415 p 0001 concomitant autoimmune disease occurred 191 vs 49 p 0001 patients nmosd vs nonnmosd controls nmosd patients incurred significantly higher total median interquartile range healthcare costs per patient 68 38648 23 37354160 86270 matched nonnmosd controls autoimmune disease 17 21513 67154831 44193 p 0001 patients nmosd without autoimmune comorbidity 23 90542 86328267 25154 p 0022 similarly patients nmosd nonautoimmune comorbidities incurred higher median healthcare costs matched controlsconclusions patients nmosd experience significant disease burden cost amplified comorbidities effective therapies needed particularly patients concomitant autoimmune diseasepmid34111762 doi101016 jjns2021117530,0.0
mast cell tryptase release contributes disease progression lymphangioleiomyomatosis j respir crit care med 2021 apr 21 doi 101164 rccm2020072854oc online ahead printabstractrationale lymphangioleiomyomatosis multisystem disease causing lung cysts respiratory failure loss tuberous sclerosis complex tsc gene function results clone lam cells dysregulated mtor activity lam cells fibroblasts form lung nodules also contain mast cells although significance unknownobjectives understand mechanism mast cell accumulation role pathogenesis lam methods measurements main results transcriptional profiling quantitative rtpcr elisa showed lam derived cell fibroblast cocultures induced multiple cxc chemokines fibroblasts compared normal tissue lam lungs increased tryptase positive mast cells expressing cxc chemokine receptors p005 mast cells located around periphery lam nodules positively associated rate lung function loss p0016 vitro lam spheroid tsc2 null cell fibroblast cocultures attracted mast cells inhibited pharmacologic crisprcas9 inhibition cxcr1 2 lam spheroids caused mast cell tryptase release induced fibroblast proliferation increased lam spheroid size 136024 fold p00019 tryptase inhibitor apc366 sodium cromoglycate inhibited mast cell induced spheroid growth using immunocompetent tsc2 null murine homograft model sodium cromoglycate markedly reduced mast cell activation tsc2 null lung tumour burden vehicle 3253236 cromoglycate 5543 p00035 conclusions lam cell fibroblast interactions attract mast cells tryptase release contributes disease progression repurposing sodium cromoglycate use lam studied alternative adjunct mtor inhibitor therapypmid33882264 doi101164 rccm2020072854oc,0.0
personalizing ocrelizumab treatment multiple sclerosis can learn sarscov2 pandemic j neurol sci 2021 may 20 427117501 doi 101016 jjns2021117501 online ahead printabstractduring sarscov2 pandemic adopted personalized delayed protocol ocrelizumab infusions relapsing remitting multiple sclerosis rrms patients according national recommendations 83 rrms patients whose infusion scheduled march december 2020 56 patients experienced delay treatment based ms severity sarscov2 infection risk profile cases immunophenotype performed monthly guide reinfusions specifically b cd19 + cells repopulation rate monitored mean infusion delay 103 1 sd 40 6 days none patients presented relapses active disease mri end observation period treatment nave status interval immunophenotyping last ocrelizumab infusion predictors earlier b cd19 + cells repopulation two patients contracted sarscov2 complete recovery definitive data sarscov2 vaccine efficacy patients treated ocrelizumab still lacking findings suggest personalized treatment delayed infusion schedule compromise ocrelizumab shortterm efficacy may help lengthen therapeutic window effective response sarscov2 vaccinepmid34044238 doi101016 jjns2021117501,0.0
world brain day 2021 campaign continue gain momentum join us stop multiple sclerosis j neurol sci 2021 jun 19 427117547 doi 101016 jjns2021117547 online ahead printno abstractpmid34216976 doi101016 jjns2021117547,0.0
update management multiple sclerosis covid19 pandemic post pandemic international consensus statement j neuroimmunol 2021 jun 7 357577627 doi 101016 jjneuroim2021577627 online ahead printabstractin consensus statement provide updated recommendations multiple sclerosis ms management covid19 crisis postpandemic period applicable neurology services around world statements recommendations generated based available literature experience 13 ms expert panelists using modified delphi approach online statements recommendations give advice regarding implementation telemedicine use diseasemodifying therapies management ms relapses management people ms highest risk covid19 management radiological monitoring use remote pharmacovigilance impact ms research implications lowest income settings key issuespmid34139567 doi101016 jjneuroim2021577627,0.0
molecular cellular basis copper dysregulation relationship human pathologies abstractcopper cu essential micronutrient required activity redoxactive enzymes involved critical metabolic reactions signaling pathways biological functions transporters chaperones control cu ion levels bioavailability ensure proper subcellular systemic cu distribution intensive research focused understanding mammalian cells maintain cu homeostasis molecular signals coordinate cu acquisition storage within organs humans mutations genes regulate cu homeostasis facilitate interactions cu ions lead numerous pathologic conditions malfunctions cu+transporting atpases atp7a atp7b cause menkes disease wilson disease respectively additionally defects mitochondrial cellular distributions homeostasis cu lead severe neurodegenerative conditions mitochondrial myopathies metabolic diseases cu dual nature carcinogenesis promotor tumor growth inducer redox stress cancer cells cu also plays role cancer treatment component drugs regulator drug sensitivity uptake review provide overview current knowledge cu metabolism transport relation various human pathologies,0.0
role lung ultrasound blines serum kl6 screening followup rheumatoid arthritis patients identification interstitial lung disease review literature proposal preliminary algorithm clinical application cases abstractscreening followup interstitial lung disease associated rheumatoid arthritis raild challenge clinical practice fact majority raild patients asymptomatic optimal tools early screening regular followup lacking furthermore patients may remain oligosymptomatic despite significant radiological abnormalities raild usual interstitial pneumonia uip frequent radiological pathological pattern associated poor prognosis high risk develop acute exacerbations infections raild can identified early may opportunity early treatment close followup might delay ild progression improve longterm outcomein connective tissue diseaseassociated interstitial lung disease ctdild lung ultrasound lus assessment blines serum krebs von den lungen6 antigen kl6 recognized sensitive biomarkers early detection ild bline number serum kl6 level found correlate highresolution computed tomography hrct pulmonary function tests pfts clinical parameters systemic sclerosisassociated ild sscild recently significant correlation blines kl6 two nonionizing noninvasive biomarkers demonstrated hence combined use lus kl6 screen follow ild ra patients might useful clinical practice addition existing tools herein review relevant literature support concept propose preliminary screening algorithm present 2 cases algorithm used,0.0
functional structural mri correlates executive functions multiple sclerosis abstractbackgroundexecutive dysfunctions including difficulties attention working memory planning inhibition affect 1528 multiple sclerosis ms patientsobjectivesto investigate structural functional magnetic resonance imaging mri abnormalities underlying executive function ef ms patientsmethodsa total 116 ms patients 65 controls underwent restingstate rs diffusionweighted sequences neuropsychological examination including wisconsin card sorting test wcst test ef brain rs cognitive networks fractional anisotropy fa priori selected white matter tracts derived associations wcst scores rs functional connectivity fc fa abnormalities investigatedresultsin ms patients predictors working memory updating lower corpus callosum cc fa lower left workingmemory network wmn right wmn rs fc worse performance lower executive control network ecn higher defaultmode network dmn salience network sn rs fc better performance r2035 predictors attention lower cc genu fa lower left wmn dmn rs fc worse performance higher left wmn ecn rs fc better performance r2024 predictors worse shifting inhibition lower cc genu superior cerebellar peduncle scp fa lower left wmn rs fc worse performance higher ecn rs fc better performance r2024 conclusionscc scp microstructural damage rs fc abnormalities cognitive networks underlie ef frailty ms,0.0
osteoporosis associated varus deformity postmenopausal women knee osteoarthritis crosssectional study background varus deformity knee common pathological characteristic knee osteoarthritis koa enough attention given relationship knee varus deformity state systemic bone mass purpose study evaluate potential relationship bone mineral density bmd varus deformity postmenopausal women koamethodsa total 202 postmenopausal women koa kl grade 2 department january 2018 june 2020 reviewed crosssectional study hipkneeankle angle lower extremity hka medial distal femoral angle mdfa medial proximal tibial angle mpta angle joint line jlca measured patients according hka angle participants divided varus deformity group hka 1753 normal limb alignment group 1753 hka 1803 bmd lumbar l1l4 left femoral neck left hip measured dualenergy xray absorptiometry patients difference bmd knee varus deformity group normal limb alignment group compared relationship different angles limb alignment bmd values different sites evaluatedresultsthere 144 cases 713 varus deformity group 58 cases 287 normal limb alignment group bmd different joint sites within knee varus deformity group lower normal limb alignment group prevalence osteoporosis higher adjusting confounding factors age bmi pain duration affected side binary logistic regression showed osteoporosis independent risk factor varus deformity koa multiple linear regression showed bmd spine femoral neck hip significantly associated varus deformity koa pearson correlation analysis showed bmd lumbar spine l1l4 left femoral neck left hip joint positively correlated hka negatively correlated jlca mpta positively correlated left femoral neck left hip joint bmd correlated lumbar bone density furthermore normal limb alignment group hka negatively correlated jlca significantly correlated mdfa mpta varus deformity group hka negatively correlated jlca also positively correlated mdfa mptaconclusionsosteoporosis major risk factor varus deformity postmenopausal women koa progression varus deformity knee concerned postmenopausal women simultaneously koa osteoporosis,0.0
effect national diseasemodifying therapy subsidy policy longterm disability outcomes people multiple sclerosis abstractbackgrounddiseasemodifying therapies dmts used treat people relapsingonset multiple sclerosis roms knowledge largely limited shortterm effectsobjectiveto determine 1 impact nationallevel dmt subsidy policy dmt use health outcomes people ms pwms 2 longterm effects dmt disability quality life qol 5level eq5d version eq5d5l utility value methodsthis observational cohort study compared australian new zealand populations different levels dmt availability 1020years postroms diagnosis betweencountry differences assessed using standardised differences associations assessed multivariable linear regression modelsresultswe recruited 328 australians 256 new zealanders australian cohort longer dmt treatment duration greater proportion disease course treated shorter duration diagnosis starting dmt australian cohort lower median expanded disability status scale edss 35 vs 40 multiple sclerosis severity score msss 305 vs 371 higher qol 071 vs 065 multivariable models betweencountry differences disability qol largely attributed differential use dmtconclusionsthis study provides evidence impact nationallevel dmt policy disability outcomes pwms dmts accessible pwms experienced less disability progression improved qol 1020years postdiagnosis,0.0
assessment disease activity using wholebody mri derived radiological activity index chronic nonbacterial osteomyelitis background based recently developed chronic nonbacterial osteomyelitis mri scoring tool cromris developed radiological activity index raicromris obtain quantification overall bone involvement individual patientsmethodswhole body magnetic resonance imaging wbmri images scored according parameters included raicromris bone marrow hyperintensity signal extension soft tissue periosteal hyperintensity bony expansion vertebral collapse parameters evaluated bone unit yielding score 0 7 summed raicromris including bone units assessed clinical disease activity using physician global assessment pga radiological findings 76 treatmentnave patients 46 76 evaluated 6 12 months initial wbmri quantitative variables compared using mannwhitney u test unmatched groups wilcoxon signedrank test paired groups correlation evaluated using spearmans rank coefficient rs resultsthere significant correlation raicromris pga rs 032 p 00055 raicromris presence elevated erythrocyte sedimentation rate p 0013 creactive protein p 00001 baseline raicromris decreased median 17 baseline 12 6 months p 0004 remained stable median 11 12 months correlation raicromris pga observed baseline rs 041 p 0004 follow 6 months rs 033 p 0025 12 months rs 038 p 0010 baseline raicromris median 20 significantly higher patients subsequently received bisphosphonates patients received treatments median 12 decreased significantly bisphosphonates p 0008 conclusionsthe raicromris correlated clinical laboratory measures disease activity showing significant shortterm changes following treatment bisphosphonates tool used clinical practice clinical trials validation,0.0
prevalence multiple sclerosis rosario argentina abstractbackgroundthe prevalence incidence multiple sclerosis increasing worldwide last decades publications last years outstand prevalence europe north america latin america argentina data published topic scarce studies took place buenos aires recent publication reported ms prevalence rate 303 100 000 overall extension santa fe argentina study noticed ms seemed frequent southern region provinceobjectivein study aimed estimate prevalence ms rosario third populated district argentina placed southeastern part santa fe provincemethodsthis population based crosssectional study studied members provinces medical care program health maintenance organization publicsector employees offers medical health services 567 819 members province 163 513 permanent residence rosario department large representative sample selected prevalence date 30 june 2019 cases ms detected thorough search electronic databases affiliates linking aggregating datasetsresultsseventynine ms cases detected mean age 477 sd 135 female male ratio 3 1 frequent phenotype relapsingremitting 823 followed secondaryprogressive 152 primaryprogressive 25 crude prevalence rate ms rosario 30 june 2019 483 100 000 inhabitants 95 ci 4828 4835 637 100 000 females 283 100 000 males agestandardised ms prevalence rate 434 100 000 inhabitants 95 ci4337 4343 sexstandardised prevalence estimated 467 100 000 inhabitants 95 ci 4668 4674 making proportional linear projection total number inhabitants deemed total 578 ms cases rosario according 2010 census projected 620 cases july 2019conclusionthis first study provides epidemiological data ms prevalence rosario confirms differences distribution ms santa fe favour aggregation cases southern part province also supplies updated relevant data distribution ms argentina latin america,0.0
experiences sexual gender minority people living multiple sclerosis northern california exploratory study abstractbackgroundsexual gender minority sgm individuals may face unique challenges accessing quality medical care due structural disparities social discrimination lack culturally competent healthcare multiple sclerosis ms requires complex care little research carried intersection sgm identity ms careobjectiveto identify unmet clinical social needs clinical population sgm patients msmethodspatients ms selfidentified sgm recruited ucsf ms center national ms society web post complete 45minute webbased qualtrics survey mixed qualitative quantitative survey covered experiences different domains ms care drug alcohol use relationship status social support participation ms sgm communitiesresultsamong 26 survey respondents mean age 502 sd 106 years gender identity women 46 men 38 genderqueer transgender 15 sexual orientation gay lesbian bisexual 35 pansexual queer 27 questioning 23 identity 15 two thirds 69 respondents partnered overall satisfaction ms care high 792 participants scored 4 5 somewhat extremely satisfied participants dissatisfied care cited feeling dismissed 875 felt sgm identities affect ms care still 30 report feeling uncomfortable discussing sgm identities clinician participants rated low impact ms participation sgm communities mean 24 5 likert scale participants reporting higher impact cited fatigue immobility stigmatization disease primary factors similarly sgm status low effect participation ms community mean 14 5 higher impact related apprehension around identity disclosure new groups identified resources might improve ms care included representation inclusivity openness clinicians sgmfocused ms support groupsdiscussionin exploratory survey needs sgm people living ms northern california participants reported unlikely participate activities sgm community due ms status symptoms however felt sgm status affect ms care given centernulls location hub sgm community activism surveying individuals settings provide greater insights role community clinical support experience sgm people living ms,0.0
neuroinflammation autoimmune disease primary brain tumors quest striking right balance front cell neurosci 2021 aug 13 15716947 doi 103389 fncel2021716947 ecollection 2021abstractaccording classical dogma central nervous system cns defined immune privileged space basis theory rooted incomplete understanding cns microenvironment however recent advances identification resident dendritic cells dc brain presence cns lymphatics deepened understanding neuroimmune axis revolutionized field neuroimmunology now understood many pathological conditions induce immune response cns many ways cns immunologically distinct organ hyperactivity neuroimmune axis can lead primary neuroinflammatory diseases multiple sclerosis antibodymediated encephalitis whereas immunosuppressive mechanisms promote development survival primary brain tumors therapeutic front attempts made target cns pathologies using various forms immunotherapy one actively investigated areas cns immunotherapy treatment glioblastoma gbm common primary brain tumor adults review provide date overview neuroimmune axis steady state discuss mechanisms underlying neuroinflammation autoimmune neuroinflammatory disease well development progression brain tumors addition detail current understanding interactions characterize primary brain tumor microenvironment implications neuroimmune axis development successful therapeutic strategies treatment cns malignanciespmid34483843 pmcpmc8414998 doi103389 fncel2021716947,0.0
supratentorial nonrela zftafused ependymomas comprehensive phenotype genotype correlation highlighting number zinc fingers zftancoa1 2 fusions abstractthe cimpactnow update 7 replaced nosology ependymoma rela fusion positive supratentorialependymoma c11orf95fusion positive modification reinforces idea supratentorialependymomas exhibiting fusion implicates c11orf95 now called zfta gene without rela gene represent histomolecular entity hot press molecular study identified distinct clusters dna methylation class zfta fusionpositive tumors interestingly clusters 2 4 comprised tumors different morphologies various zfta fusions without involvement rela paper present detailed series thirteen cases nonrela zftafused supratentorial tumors extensive clinical radiological histopathological immunohistochemical genetic epigenetic dna methylation profiling characterization contrary age onset mri aspects similar rela fusionpositive epn noted significant histopathological heterogeneity pleomorphic xanthoastrocytomalike astroblastomalike ependymomalike even sarcomalike patterns cohort immunophenotypically nfb immunonegative tumors expressed gfap variably ema constantly l1cam frequently different gene partners fused zfta ncoa1 2 maml2 first time mn1 tumors epigenetic homologies within dna methylation class ependymomasrela classified satellite clusters 2 4 cluster 2 n 9 corresponded tumors classic ependymal histological features n 4 also astroblastic features n 5 various types zfta fusions associated cluster 2 original report zftamaml2 fusion frequent cluster 4 enriched sarcomalike tumors moreover reported novel anatomy three zftancoa1 2 fusions 1 zfta zinc finger domain putative fusion protein whereas previously reported nonrela zfta fusions 4 zfta zinc fingers three cases presented sarcomalike morphology genotype phenotype association requires studies confirmation series first extensively characterize new subset supratentorial zftafused ependymomas highlights usefulness zfta fish analysis confirm existence rearrangement without rela abnormality,0.0
pi3kinase p110 deficiency modulates t cell homeostasis function attenuates experimental allergic encephalitis mature mice int j mol sci 2021 aug 13 22 16 8698 doi 103390 ijms22168698abstractclass phosphoinositide 3kinases pi3k involved development normal autoimmune responses including experimental autoimmune encephalomyelitis eae mouse model human multiple sclerosis ms role ubiquitously expressed class ia pi3k p110 catalytic subunits eae analyzed using model cre flox mediated t cell specific deletion p110 catalytic chain p110t comparison two monthold young six monthold mature p110t mice wild type wt counterparts indicated loss spleen cd4+ t cells increased age indicating role p110 homeostasis contrast cd4+ t regulatory treg cells enhanced mature p110t mice compared wt mice since myelin oligodendrocyte glycoprotein mog peptideinduced eae dependent mediated cd4+ t cells cd4+ t cellderived cytokines controlled treg cells development eae young mature wt p110t mice analyzed eae clinical symptoms disease scores six month p110t mice significantly lower mature wt young wt p110t mice furthermore ex vivo antigen activation lymph node cells mog immunized mature p110t mice induced significantly lower levels ifn il17a young p110t young mature wt mice cytokines including il2 il10 tnf showed significant differences p110t wt mature mice data show lower incidence moginduced eae mature p110t mice linked altered t cell homeostasis lower secretion inflammatory cytokinespmid34445401 doi103390 ijms22168698,1.0
ocrelizumab treatment relapsingremitting multiple sclerosis suboptimal response previous diseasemodifying therapy nonrandomized controlled trial abstractbackgroundmany patients multiple sclerosis ms experience suboptimal disease control despite use diseasemodifying therapy dmt objectiveto assess efficacy safety ocrelizumab ocr patients relapsingremitting ms rrms suboptimal response prior dmtsmethodspatients rrms suboptimal responses one clinically reported relapse lesion activity after6months another dmt enrolled ocr 600mg given intravenously every 24weeks primary outcome evidence disease activity neda defined absence protocoldefined relapse confirmed disability progression cdp t1 gdenhancing lesions new enlarging t2 lesionsresultsthe intentiontotreat itt population included 608 patients neda analyzed modified itt mitt population n576 947 96weeks 481 mitt patients achieved neda free protocoldefined relapse 896 cdp 896 t1 gdenhancing lesions 955 595 new enlarging t2 lesions safety observations consistent findings pivotal trialsconclusionconsistent efficacy ocr clinical magnetic resonance imaging mri disease activity measures progression shown patients rrms suboptimal response prior dmts new safety signals observed,1.0
editorial neuroinflammation visual system front neurol 2021 aug 13 12724447 doi 103389 fneur2021724447 ecollection 2021no abstractpmid34484107 pmcpmc8409521 doi103389 fneur2021724447,0.0
exosomes secreted microglia virus infection central nervous system activate inflammatory response bystander cells front cell dev biol 2021 aug 13 9661935 doi 103389 fcell2021661935 ecollection 2021abstractmicroglia become persistently infected theilers murine encephalomyelitis virus tmev infection central nervous system cns susceptible mice previously shown microglia infected tmev become activated innate immune receptors express type interferons cytokines chemokines persistent tmev infection cns promotes chronic neuroinflammation development demyelinating disease similar multiple sclerosis current studies wanted determine whether tmevinfected microglia secrete exosomes contribute neuroinflammation cns thus promoting development demyelinating disease exosomes vesicles containing rna dna proteins released one cell taken another cell facilitate communication cells studies isolated exosomes secreted microglia tmev infection vitro well exosomes secreted microglia early tmev infection mice studies show microglia secrete exosomes tmev infection contain viral rna coding region exosomes secreted microglia tmev infection can taken uninfected bystander cells including cns resident microglia astrocytes neurons viral rna exosomes can transferred bystander cells addition bystander cells took exosomes activated innate immune response express type interferons ifn ifn proinflammatory cytokines il6 il12 tnf chemokines ccl2 interestingly exosomes secreted microglia early tmev infection mice activated inflammatory response transferred brains nave mice results show exosomes secreted microglia early tmev infection contain viral rna can activate uninfected bystander cns cells promote inflammatory immune response thus exosomes secreted microglia virus infection may promote viral persistence neuroinflammation contributes development demyelinating diseasepmid34485270 pmcpmc8415116 doi103389 fcell2021661935,1.0
growth differentiation factor 15 associated alzheimer#39 s disease risk front genet 2021 aug 13 12700371 doi 103389 fgene2021700371 ecollection 2021abstractbackground previous observational studies suggested associations exist growth differentiation factor 15 gdf15 neurodegenerative diseases aimed investigate causal relationships gdf15 alzheimers disease ad parkinsons disease pd amyotrophic lateral sclerosis als methods using summarylevel datasets genomewide association studies european ancestry performed twosample mendelian randomization mr study genetic variants significantly associated p 5 108 gdf15 selected instrumental variables n 5 inversevariance weighted method implemented primary mr approach weighted median mregger leaveoneout analysis cochrans qtest conducted sensitivity analyses analyses performed using r 361 relevant packagesresults mr provided evidence association elevated gdf15 levels higher risk ad odds ratio 114 95 confidence interval 104124 p 0004 reverse direction mendelian randomization suggested causal effect genetically proxied risk ad circulating gdf15 p 0450 causal effects gdf15 pd p 0597 als p 0120 identified mr results likewise support association genetic liability pd als genetically predicted levels gdf15 evident heterogeneity horizontal pleiotropy revealed multiple sensitivity analysesconclusion highlighted role gdf15 ad altogether promising diagnostic marker therapeutic targetpmid34484296 pmcpmc8414585 doi103389 fgene2021700371,0.0
humoral response sarscov2 mrna vaccine patients multiple sclerosis treated natalizumab ther adv neurol disord 2021 aug 13 1417562864211038111 doi 101177 17562864211038111 ecollection 2021no abstractpmid34413902 pmcpmc8369851 doi101177 17562864211038111,0.0
cluster randomized trial interferon 1a reduction transmission sarscov2 protocol containing coronavirus disease 19 trial concord19 background sarscov2 infection rapidly spreads populations due high rates community transmission interrupting shedding sarscov2 may reduce incidence coronavirus disease 19 covid19 herein provide protocol cluster randomized trial will examine effectiveness treatment interferon ifn 1a compared standard care limiting transmission sarscov2 coprimary objectives determine whether ifn therapy reduces proportion infected cases shedding sarscov2 day 11 post randomization b incidence transmission sarscov2 infection index cases treatmenteligible household postexposure contacts day 11 randomization secondary objectives include assessing impact ifn treatment duration viral clearance hospitalizations fatalities evaluating safety ifn treatmentmethodsthree hundred ten households including index case recent covid19 diagnosis least one asymptomatic treatmenteligible household contact will randomized receive 3 doses 125 g ifn 1a subcutaneous administration days 1 6 11 standard care participants will followed day 29discussionthe results trial will identify whether ifn treatment mild moderate covid19 cases accelerates viral clearance prevents disease progression whether ifn treatment postexposure contacts covid19 cases reduces transmission infectiontrial registration trial registered clinicaltrialsgov nct04552379 date registration september 17 2020,0.0
taurelated grey matter network breakdown across alzheimers disease continuum background changes grey matter covariance networks reported preclinical clinical stages alzheimers disease ad associated amyloid deposition cognitive decline however role tau pathology grey matter networks remains unclear based previously reported associations tau pathology synaptic density brain structural measures taurelated connectivity changes across different stages ad might expected aimed assess relationship tau aggregation grey matter network alterations across ad continuummethodswe included 533 individuals 178 anegative cognitively unimpaired cu subjects 105 apositive cu subjects 122 apositive patients mild cognitive impairment 128 patients ad dementia biofinder2 study singlesubject grey matter networks extracted t1weighted images graph theory properties including degree clustering coefficient path length small world topology calculated associations tau positron emission tomography pet values global regional network measures examined using linear regression models adjusted age sex total intracranial volume finally tested whether association tau pathology cognitive performance mediated grey matter network disruptionsresultsacross whole sample found higher tau load temporal metaroi associated significant changes degree clustering path length small world values p 0001 indicative less optimal network organisation already cu apositive individuals associations tau burden lower clustering path length observed whereas advanced disease stages elevated tau pathology progressively associated brain network abnormalities moreover association higher tau load lower cognitive performance partly mediated 93 95 small world topologyconclusionsour data suggest close relationship grey matter network disruptions tau pathology individuals abnormal amyloid might reflect reduced communication neighbouring brain areas altered ability integrate information distributed brain regions tau pathology indicative random network topology across different ad stages,0.0
study protocol advance care planning multiple sclerosis concuresm intervention construction multicentre feasibility trial bmj open 2021 aug 13 11 8 e052012 doi 101136 bmjopen2021052012abstractintroduction multiple sclerosis ms common cause progressive neurological disability young adults use advance care planning acp people progressive ms pwpms remains limited concuresm project aims assess effectiveness structured acp intervention pwpms intervention consists training programme acp healthcare professionals caring pwpms booklet used acp conversation herein describe first two project phasesmethods phase 1 translated adapted italian legislation ms context acp booklet national acp programme new zealand acceptability comprehensibility usefulness booklet assessed via 13 personal cognitive interviews pwpms significant others sos one health professional focus group based findings will revise booklet phase 2 will conduct singlearm pilot feasibility trial nested qualitative study participants will 40 pwpms sos health professionals six ms rehabilitation centres italy 6 months following acp conversation will assess completion advance care plan document primary outcome well safety intervention secondary outcomes will range measures capture full process acp patientcarer congruence treatment preferences quality patientclinician communication caregiver burden qualitative process evaluation will help understand factors likely influence future implementation scalability interventionethics dissemination project coleaded neurologist bioethicist phase 1 received ethical approvals participating centre phase 2 will submitted centres may 2021 findings phases will disseminated widely peerreviewed publications conferences workshopstrial registration number isrctn48527663 preresultspmid34389580 doi101136 bmjopen2021052012,0.0
first exposure rituximab associated high rate antidrug antibodies systemic lupus erythematosus ancaassociated vasculitis background antidrug antibodies adas can impact efficacy safety biologicals today used treat several chronic inflammatory conditions specific patient groups may prone develop adas rituximab routinely used ancaassociated vasculitis aav offlabel therapy systemic lupus erythematosus sle data occurrence predisposing factors adas diseases limitedobjectivesto elucidate rate occurrence risk factors adas rituximab sle aavmethodsadas detected using bridging electrochemiluminescent ecl immunoassay sera rituximabnave aav n 41 sle n 62 rituximabtreated aav n 22 sle n 66 patients clinical data retrieved medical records disease activity estimated sle disease activity index2000 sledai2 k birmingham vasculitis activity score bvas resultsafter first rituximab cycle aav patients adapositive compared 378 sle patients samples obtained median iqr time 55 3770 months aav 60 5070 months sle adapositive sle individuals younger 340 259408 vs 443 327563 years p 0002 active disease sledai2 k 140 100185 vs 80 6014 p 00017 shorter disease duration 414 1181008 vs 919 5711693 p 00097 compared adanegative sle adas primarily occurred nephritis patients associated antidsdna positivity influenced concomitant use corticosteroids cyclophosphamide previous treatmentsdespite overall reduction sledai2 k 120 7016 40 2067 p 00001 adapositive individuals still higher sledai2 k 60 4090 vs 40 2060 p 0004 b cell count 6 months followup higher cd19 + 40 05100 vs 05 0410 p 0002 retreatment two adapositive sle patients developed serum sickness 167 three infusion reactions 25 contrast one 52 serum sickness adanegative groupconclusionsin contrast aav adas highly prevalent among rituximabtreated sle patients already first course treatment found effect clinical immunological responses high frequency sle may warrant implementations ada screening retreatment survey immediate lateonset infusion reactions,0.0
gender gap leadership health institutions influence hospitallevel factors health equity 2021 aug 13 5 1 521525 doi 101089 heq20210013 ecollection 2021abstractobjective analyze whether increased representation women health field accompanied greater presence leadership positions public health system whether differences according hospital level methods descriptive study distribution leadership positions sex type hospital within health centers regional public health system results total 7401 professionals women representation women management positions 331 among service chiefs 2401 service headings observed surgical specialties lower representation women 309 medical specialties vs 181 surgical specialties p00001 type hospital differences found management positions differences medical chiefs less female representation regional hospitals 286 vs 397 p0003 conclusion women represent majority public health system nonetheless representation positions greater responsibility decisionmaking limited particularly low county hospitals increasing female representation positions current challenge society equality policies need developed applied minimize gender gappmid34476325 pmcpmc8409238 doi101089 heq20210013,0.0
pathogenic role ckit+ mast cells spinal motor neuronvascular niche als abstractdegeneration motor neurons glial cell reactivity vascular alterations cns important neuropathological features amyotrophic lateral sclerosis als immune cells trafficking blood also infiltrate affected cns parenchyma contribute neuroinflammation mast cells mcs hematopoieticderived immune cells whose precursors differentiate upon migration tissues upon activation mcs undergo degranulation ability increase vascular permeability orchestrate neuroinflammation modulate neuroimmune response however prevalence pathological significance pharmacology mcs cns als patients remain largely unknown autopsy als spinal cords identified first time mcs express ckit together chymase tryptase cox2 display granular degranulating morphology compared scarce mcs control cords als mcs mainly found niche spinal motor neuron somas nearby microvascular elements displayed remarkable pathological abnormalities similarly mcs accumulated motor neuronvascular niche als murine models vicinity astrocytes motor neurons expressing ckit ligand stem cell factor scf suggesting scf ckitdependent mechanism mc differentiation precursors mechanistically provide evidence fully differentiated mcs cell cultures can generated murine als spinal cord tissue supporting presence ckit+ mc precursors moreover intravenous administration bone marrowderived ckit+ mc precursors infiltrated spinal cord als mice controls consistent aberrant trafficking defective microvasculature pharmacological inhibition ckit masitinib als mice reduced mc number influx mc precursors periphery results suggest previously unknown pathogenic mechanism triggered mcs als motor neuronvascular niche might targeted pharmacologically,0.0
roles physical exercise neurodegeneration reversal epigenetic clock abstractthe epigenetic clock defined dna methylation dnam level extensively applied distinguish biological age chronological age agingrelated neurodegeneration associated epigenetic alteration determines status diseases recent years extensive research shown physical exercise pe can affect dnam level implying reversal epigenetic clock neurodegeneration pe also regulates brain plasticity neuroinflammation molecular signaling cascades associated epigenetics review summarizes effects pe neurodegenerative diseases via general diseasespecific dnam mechanisms discusses epigenetic modifications alleviate pathological symptoms diseases may lead probing underpinnings neurodegenerative disorders provide valuable therapeutic references cognitive motor dysfunction,0.0
cognitive fatigue interventions people multiple sclerosis scoping review abstractbackgroundfatigue common symptom experienced people multiple sclerosis ms can categorized physical cognitive fatigue existing body literature mostly focuses physical fatigue ms limited research cognitive fatigue interventions effectively manage cognitive fatigue cohort therefore aim scoping review identify summarize available research literature different types interventions manage cognitive fatigue provide comprehensive perspective treatment optionsmethodsthe prisma extension scoping reviews methodology used searches conducted may 2021 following databases cinahl plus full text medline via ovid psycinfo embase via ovid proquest dissertations theses global inclusion criteria peerreviewed journal articles written english french included intervention manage ms cognitive fatigue search keywords included multiple sclerosis cognitive fatigue intervention retrieved citationsnull titles abstracts screened eligible articles fully reviewed two reviewers included studies categorized based type intervention effect size calculated estimate effectiveness interventionsresultsof 653 retrieved citations 34 retained review participants included studies mostly middleaged adults relapsingremitting ms without severe mobility issues living ms 10 years average majority studies randomized controlled trials n17 followed pilot feasibility trials n4 casecontrol n2 experimental designs n11 interventions categorized educational programs selfmanagement programs diet counselling n18 medical pharmacological monoaminergic stabilizers natalizumab dalfampridine n6 exercise physical interventions resistance training aquatic exercise walking n10 included interventions fatigue selfmanagement interventions incorporate educational materials involve trained facilitators seem optimal reducing negative effects cognitive fatigueconclusionthis review identified variety interventions ms cognitive fatigue management however sufficient evidence leading clear recommendation appropriate effective approaches cognitive fatigue management research field needed,0.0
characterizing gaze postural stability deficits people multiple sclerosis abstractbackgroundpeople multiple sclerosis pwms experience wide range symptoms can alter function limit activity community participation symptoms including sensory changes weakness fatigue others well documented however symptoms related changes vestibular related function including gaze postural stability fully explored recent studies begun provide insight deficits pwms explored use rehabilitation paradigms management much remains unknown full extent deficits therefore study aimed characterize presence gaze postural stability deficits measures across world health organization international classification functioning disability health icf examine deficits domains body structure function activity contribute participation level limitationsmethodsbaseline data 41 pwms mean sd age539 112 78 female enrolled part randomized clinical trial used analysis measures gaze postural stability icf domains body structure function vestibular ocular reflex vor gain postural sway area activity computerized dynamic visual acuity cdva minibest test participation dizziness handicap inventory dhi activities balance confidence abc scale along demographic data used characterize sample explore relationships icf domains gaze postural stability univariate correlations performed measures domain using pearsonnulls correlations separate multivariate regression models examined measures body structure function activity domains contributed variance participation level outcomes variance explained models quantified using rsquared statistic contribution independent variables quantified using beta coefficient p005 resultscorrelation analysis demonstrated significant relationships postural stability measures across domains specifically postural sway area firm surface minibest test score r48 p001 minibest test score abc score r05 p001 significant correlations also found gaze stability measures horizontal vertical vor gain r68 p0001 horizontal vor gain dynamic visual acuity r38 p002 vertical vor gain dynamic visual acuity r54 p0001 regression models assessing postural stability found minibest score significantly contributed variance abc score p001 full model explained 34 variance abc score regression modeling gaze stability outcomes produce variable significantly contributed variance dhi score full model explained 18 variance dhi scoreconclusionspwms sample demonstrated deficits gaze postural stability across domains icf compared past samples pwms healthy cohorts correlation measures different domains present strong relationship measures body structure function activity participation level outcomes observed lack relationship across domains likely contributed relatively small sample size high level variability observed outcomes diverse presentation often seen pwms,0.0
multiple sclerosis presenting sixth nerve palsy child int med case rep j 2021 aug 13 14545550 doi 102147 imcrjs320678 ecollection 2021abstractwe report child multiple sclerosis presented sixth nerve palsy twelveyearold bahraini female presented ophthalmology department complaining double vision also imbalance paraesthesia extraocular muscle examination showed restriction abduction right eye change vision mri showed right eye optic neuritis demyelination indicative multiple sclerosis ms ocular coherence tomography oct showed thinning nerve fibres eyes consistent subclinical optic neuritis neurological examination showed brisk knee jerk left side incoordination movement side disability status scale edss showed score 30 given solumedrol 500 mg intravenously iv addition omeprazole 40 mg iv vitamin d3 cholecalciferol 50 000 iu cap weekly 8 weeks neurorubine forte tablets vitamin b1 6 12 day 2 months became asymptomatic followup visits children ms can present sixth cranial nerve palsy clinicians high index suspicion early diagnosis treatment addition mri oct useful diagnostic tool optic neuritis ms especially childrenpmid34413685 pmcpmc8370490 doi102147 imcrjs320678,1.0
prevention eae tolerogenic vaccination pegylated antigenic peptides ther adv chronic dis 2021 aug 12 1220406223211037830 doi 101177 20406223211037830 ecollection 2021abstractbackground therapeutic treatment options chronic autoimmune disorders multiple sclerosis ms rely largely use nonspecific immunosuppressive drugs able cure disease presently approaches induce antigenspecific tolerance therapeutic approach example peptidebased tolerogenic inverse vaccines regained great interest previously shown coupling peptides carriers can enhance capacity induce regulatory t cells vivomethod present study investigated whether tolerogenic potential immunodominant myelin tcell epitopes can improved conjugation synthetic carrier polyethylene glycol peg experimental autoimmune encephalomyelitis eae mouse model chronic ms mog c57bl 6 results preventive administration pegylated antigenic peptide strongly suppress development eae accompanied reduced immune cell infiltration central nervous system cns depletion regulatory t cells tregs abrogated protective effect indicating tregs play crucial role induction antigenspecific tolerance eae treatment acute phase disease safe induce immune activation however treatment peak disease affect disease course suggesting either induction tregs occur highly inflamed situation immune system refractory regulation conditionconclusion pegylation antigenic peptides effective feasible strategy improve tolerogenic treginducing peptidebased vaccines application immunotherapy overt disease might require modifications combination therapies simultaneously suppress effector mechanismspmid34408824 pmcpmc8366199 doi101177 20406223211037830,1.0
volume changes thalamus hippocampus cerebellum associated specific csf profile ms abstractbackgroundthe underlying pathogenesis surfacein grey matter abnormalities ms demonstrated neuropathology advanced mri analyses investigation might related csfmediated mechanism inflammation damageobjectiveto examine link csf inflammatory profile damage three regions earlyinvolved ms bordering csf thalamus hippocampus cerebellummethodsin longitudinal prospective study evaluated 109 relapsingremitting ms patients diagnosis 2year followup association baseline csf level 19 inflammatory mediators volume changes thalamus hippocampus cerebellar cortex control regions globus pallidus putamen resultsthe multivariable analysis showed cxcl13 scd163 csf levels baseline independent predictors thalamus rmodel2080 p0001 hippocampus rmodel2047 p0001 volume change 2year followup molecules plus ccl25 ifn fibrinogen independent predictors cerebellar cortex volume loss rmodel2060 p0001 independent predictors volume changes control regions foundconclusionour results indicate association csf inflammatory profile grey matter volume loss regions anatomically close csf boundaries thus supporting hypothesis surfacein gm damage ms,0.0
impaired motion perception associated functional structural visual pathway damage multiple sclerosis neuromyelitis optica spectrum disorders abstractbackgrounddecreased motion perception suggested marker visual pathway demyelination optic neuritis multiple sclerosis ms objectivesto examine influence neuroaxonal damage motion perception ms neuromyelitis optica spectrum disorders nmosd methodswe analysed motion perception numbersfrommotion nfm visual acuity multifocal mf vep optical coherence tomography patients ms n 38 confirmatory cohort n 43 nmosd n 13 healthy controls n 33 resultsnfm lower compared controls ms b 1237 p 0001 nmosd b 345 p 0001 nfm lower nonon eyes b 3095 p 0041 nmosd ms ms nmosd lower nfm associated worse visual acuity b 1394 p 0001 b 772 p 0001 low contrast letter acuity b 099 p 0002 b 16 p 0001 thinner peripapillary retinal nerve fibre layer b 10 p 0001 b 092 p 0016 ganglion cell inner plexiform layer b 648 p 0001 b 795 p 0006 vep p100 latencies confirmatory ms cohort lower nfm associated thinner retinal nerve fibre layer b 1351 p 0001 increased mfvep p100 latencies b 1159 p 0001 conclusionsstructural neuroaxonal visual pathway damage important driver motion perception impairment ms nmosd,1.0
expansion chronic ms lesions associated increase radial diffusivity periplaque white matter abstractbackgroundexpansion chronic multiple sclerosis ms lesion associated slowburning inflammation lesion rim however underlying mechanisms leading expansion fully understoodobjectiveto investigate relationship diffusivity markers demyelination axonal loss perilesional white matter lesion expansion relapsingremitting ms rrms methodst1 flair diffusion tensor images acquired 30 patients novel singlestreamline technique used estimate diffusivity lesions perilesional white matter normalappearing white matter nawm resultssignificant association found baseline periplaque radial diffusivity rd subsequent lesion expansion conversely periplaque axial diffusivity ad correlate lesion growth baseline rd ad periplaque white matter expanding lesions significantly higher compared nonexpanding lesions correlation increase rd ad periplaque area followup period lesion expansion noticeably stronger rd increase rd periplaque area also much higher compared ad significant increase ad rd periplaque area expanding nonexpanding lesionsconclusionperiplaque demyelination likely initial step process lesion expansion potentially represents suitable target remyelinating therapies,1.0
keep s#39 myelin world brain day 2021 editorial residents junior doctors pageneurology international mdpi neurol int 2021 aug 12 13 3 402403 doi 103390 neurolint13030039abstractevery five minutes someone world diagnosed multiple sclerosis pmid34449691 doi103390 neurolint13030039,1.0
factors associated brain ageing systematic review background brain age biomarker predicts chronological age using neuroimaging features deviations predicted age chronological age considered sign agerelated brain changes commonly referred brain ageing aim systematic review identify synthesize evidence association lifestyle health factors diseases adult populations brain ageingmethodsthis systematic review undertaken accordance prisma guidelines systematic search embase medline conducted identify relevant articles using search terms relating prediction age neuroimaging data brain ageing tables two recent review papers brain ageing also examined identify additional articles studies limited adult humans aged 18 years clinical general populations exposures study design types also considered eligibleresultsa systematic search identified 52 studies examined brain ageing clinical community dwelling adults mean age 21 78 years 37 female research came studies individuals diagnosed schizophrenia alzheimers disease healthy populations assessed cognitively studies psychiatric neurologic diseases commonly associated accelerated brain ageing though studies drew conclusions evidence exposures nascent relatively inconsistent heterogenous methodologies methods outcome ascertainment partly accountableconclusionthis systematic review summarised current evidence association genetic lifestyle health diseases brain ageing overall good evidence suggest schizophrenia alzheimers disease associated accelerated brain ageing evidence exposures mixed limited mostly due lack independent replication inconsistency across studies primarily cross sectional nature future research efforts focus replicating current findings using prospective datasetstrial registrationa copy review protocol can accessed prospero registration number crd42020142817,0.0
antiphospholipid antibodies neurological manifestations acute covid19 singlecentre crosssectional study abstractbackgrounda high prevalence antiphospholipid antibodies reported case series patients neurological manifestations covid19 however pathogenicity antiphospholipid antibodies covid19 neurology remains unclearmethodsthis singlecentre crosssectional study included 106 adult patients 30 hospitalised covidneurological cases 47 nonneurological covidhospitalised controls 29 covidnonhospitalised controls recruited march july 2020 evaluated nine antiphospholipid antibodies anticardiolipin antibodies acl iga igm igg antibeta2 glycoprotein1 a2gpi iga igm igg antiphosphatidylserine prothrombin aps pt igm igg antidomain 2gpi ad12gpi iggfindingsthere high prevalence antiphospholipid antibodies covidneurological 733 nonneurological covidhospitalised controls 766 contrast covidnonhospitalised controls 482 aps pt igg titres significantly higher covidneurological group compared control groups p0001 moderatehigh titre aps pt igg found 2 3 67 patients acute disseminated encephalomyelitis adem aps pt igg titres negatively correlated oxygen requirement fio2 r015 p0040 associated venous thromboembolism p0043 contrast acl iga p0001 igg p0001 associated nonneurological covidhospitalised controls compared groups correlated positively ddimer creatinine negatively fio2interpretationour findings show aps pt igg associated covid19associated adem contrast acl iga igg seen much frequently nonneurological hospitalised patients covid19 characterisation antiphospholipid antibody persistence potential longitudinal clinical impact required guide appropriate management,0.0
concerto randomized placebocontrolled trial oral laquinimod relapsingremitting multiple sclerosis abstractbackgroundinterventions targeting adaptive immune response needed multiple sclerosis ms objectiveevaluate laquinimods efficacy safety tolerability patients relapsingremitting multiple sclerosis rrms methodsconcerto randomized doubleblind placebocontrolled phase3 study rrms patients randomized 111 receive oncedaily oral laquinimod 06 12mg placebo 24months n727 n732 n740 respectively primary endpoint time 3month confirmed disability progression cdp laquinimod 12mg dose arm discontinued 1 january 2016 due cardiovascular events high doses safety monitored throughout studyresultsconcerto meet primary endpoint significant effect laquinimod 06mg versus placebo 3month cdp hazard ratio 094 95 confidence interval 067131 p0706 secondary endpoint p values nominal noninferential laquinimod 06mg demonstrated 40 reduction percent brain volume change baseline month 15 versus placebo p00001 secondary endpoint time first relapse annualized relapse rate exploratory endpoint numerically lower p00001 unexpected safety findings reported laquinimod 06mgconclusionlaquinimod 06mg demonstrated nominally significant effects clinical relapses magnetic resonance imaging mri outcomes generally well toleratedclinical trial registration numberclinicaltrialsgov nct01707992,0.0
structural functional hippocampal alterations multiple sclerosis neuromyelitis optica spectrum disorder abstractbackgroundhippocampal involvement may differ multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd objectiveto investigate morphometric diffusion functional alterations hippocampus ms nmosd clinical significancemethodsa total 752 participants including 236 ms 236 nmosd 280 healthy controls hc included retrospective multicenter study hippocampus subfield volumes fractional anisotropy fa mean diffusivity md amplitude low frequency fluctuation alff degree centrality dc analyzed associations clinical variables investigatedresultsthe hippocampus showed significantly lower volume fa greater md ms compared nmosd hc p 005 abnormal alff dc identified group hippocampal subfields affected diseases though subiculum presubiculum fimbria showed significantly lower volume ms p 005 significant correlations diffusion alterations several subfield volumes clinical variables observed diseases especially ms r 0444 0498 p 005 fa md showed fair discriminative power ms hc nmosd hc auc 07 conclusionshippocampal atrophy diffusion abnormalities identified ms nmosd partly explaining clinical disability cognitive impairment differentially affected,0.0
sustained reduction serum neurofilament light chain 7years alemtuzumab early relapsingremitting ms backgroundalemtuzumab efficacy safety demonstrated carems extension studies camms03409 topaz objectiveevaluate serum neurofilament light chain snfl carems patients highly active disease subgroup 7 2years alemtuzumab subcutaneous interferon beta1a sc ifnb1a respectivelymethodspatients received sc ifnb1a 44 g 3 week alemtuzumab 12 mg day baseline month 12 asneeded 3day courses snfl measured using singlemolecule array simoa definition 2 relapses year randomization 1 baseline gadoliniumenhancing lesionresultsbaseline median snfl levels similar alemtuzumab n 354 sc ifnb1atreated n 159 patients 317 vs 314 pg ml decreased alemtuzumab versus sc ifnb1a year 2 y2 132 vs 187 pg ml p 00001 127 pg ml alemtuzumab y7 alemtuzumabtreated patients snfl healthy control median y2 72 vs 47 p 00001 73 alemtuzumab y7 patients n 102 higher baseline snfl 494 pg ml versus overall population alemtuzumab patients attained similar levels y2 128 pg ml y7 127 pg ml 75 control median y7 conclusionalemtuzumab superior sc ifnb1a reducing snfl levels alemtuzumab patients remaining stable y7clinicaltrialsgov identifiernct00530348 nct00930553 nct02255656,0.0
cooccurrence iga nephropathy igg4tubulointersitial nephritis effectively treated tacrolimus case report background cases concurrent immunoglobulin nephropathy igan igg4related tubulointerstitial nephritis igg4tin rare previous case reports lacked important data kdigo suggests treatment systemic glucocorticoids igan patients glucocorticoids recommended firstline therapy igg4tin use tacrolimus longterm maintenance treatment described report case man developed igan igg4tin without abnormalities extrarenal tissue without renal function abnormalities impairment well treated tacrolimus longterm maintenance 45 months followupcase presentationa 56yearold chinese man first presented hospital chief complaint foamy urine 1 year hematuria 3 months medical history hypertension testing revealed notable increase serum igg4 level without abnormalities renal function imaging dysfunction organs renal biopsy showed mesangial extracellular matrix proliferation increased mesangial cell numbers infiltration plasma cells immunofluorescence showed mesangial positivity iga c3 immunohistochemistry staining showed widespread igg4 increased cd38 cd138 expression electron microscopy showed immune complexes located tubular basement membrane diagnosed igan igg4tin received glucocorticoids leflunomide tacrolimus induce remission given tacrolimus longterm maintenance treatment tacrolimus temporarily withdrawn proteinuria recurred resuming tacrolimus therapy entered complete remission 45 months therapy remains complete remission serum igg4 level normalconclusionsthe finding concurrent igan igg4tin without abnormalities renal function imaging extrarenal tissue rare coexistence may coincidental longterm treatment tacrolimus proved effective remained remission 45 months followup,0.0
multiple sclerosis circrna profile defined reveals links bcell function neurol neuroimmunol neuroinflamm 2021 aug 12 8 5 e1041 doi 101212 nxi0000000000001041 print 2021 sepabstractbackground objectives investigate total circular rna circrna profile patients relapsingremitting multiple sclerosis rrms healthy controls hcs methods hybridization microarray used define circrna profile peripheral blood mononuclear cells pbmcs 20 untreated patients rrms 10 relapse 10 remission 10 hcs analyzed close 14 000 individual circrnas per sample discovery set data validated using quantitative reverse transcriptionpcr independent cohort 47 patients rrms 19 relapse 28 remission 27 hcsresults microarray analysis revealed 914 transcripts differentially expressed patients rrms relapse hcs p 005 validated 3 circrnas 5 showing highest levels differential expression rrms relapse vs hc group hsa_circrna_101348 hsa_circrna_102611 hsa_circrna_104361 expression significantly increased relapse rrms p 00002 fc 29 p 001 fc 16 p 0001 fc 15 respectively patients showing gadolinium enhancement brain mri hsa_circrna_101348 p 00039 fc 24 hsa_circrna_104361 p 0029 fc 17 bioinformatic analysis revealed 15 micrornas interacting circrnas complementary manner led discovery validation 3 proteincoding rnas upregulated patients rrms relapse two ak2 ikzf3 previously implicated bcell functiondiscussion circrnas display distinct profile pbmcs patients rrms results may implicate circrna known disturbed bcell activity rrms thus represent novel biomarker monitoring relapse activitypmid34385287 doi101212 nxi0000000000001041,1.0
transcriptome function novel immunosuppressive autoreactive invariant natural killer t cells absent progressive multiple sclerosis neurol neuroimmunol neuroinflamm 2021 aug 12 8 6 e1065 doi 101212 nxi0000000000001065 print 2021 novabstractbackground objective aim study determine whether natural killer t nkt cells including invariant nkt cells clinical value preventing progression multiple sclerosis ms examining mechanisms distinct selfpeptide induces novel protective invariant natural killer t cell inkt cell subsetmethods performed transcriptomic functional analysis inkt cells reactive human collagen type ii selfpeptide hcii707721 measuring differentially induced genes cytokines suppressive capacityresults report first transcriptomic profile human conventional vs novel hcii707721reactive inkt cells determined hcii707721 induces protective inkt cells found blood healthy individuals progressive patients ms pms transcriptomic analysis observed hcii707721 promotes development proliferation favoring splicing fulllength akt serine threonine kinase 1 akt1 effector function unique lineage upregulating tumor necrosis factor tnf related genes furthermore hcii707721reactive inkt cells upregulate interferon ifn interleukin il 4 il10 il13 il17 rnaseq protein level unlike response glycolipid alphagalactosylceramide hcii707721reactive inkt cells increased tnf protein level suppressed autologousactivated t cells fasfas ligand fasfasl tnftnf receptor signaling tnf receptor iidiscussion based immunomodulatory properties nkt cells potential value treatment autoimmune diseases ms significant findings suggest endogenous peptide ligands can used expand inkt cells without causing cytokine storm constituting potential immunotherapy autoimmune conditions including pmspmid34385365 doi101212 nxi0000000000001065,0.0
silicacoated magnetic nanoparticles activate microglia induce neurotoxic dserine secretion background nanoparticles studied brain imaging diagnosis drug delivery owing versatile properties due small sizes however growing concerns nanoparticles may exert toxic effects brain study assessed direct nanotoxicity microglia resident macrophages central nervous system indirect toxicity neuronal cells exerted silicacoated magnetic nanoparticles containing rhodamine b isothiocyanate dye mnps sio2 ritc methodswe investigated mnps sio2 ritc induced biological changes bv2 murine microglial cells via rnasequencingbased transcriptome analysis gas chromatographymass spectrometrybased intracellular extracellular amino acid profiling morphological changes analyzed transmission electron microscopy indirect effects mnps sio2 ritc neuronal cells assessed transwellbased coculture mnps sio2 ritc treated microglia mnps sio2 ritc induced biological changes mouse brain vivo examined immunohistochemical analysisresultsbv2 murine microglial cells morphologically activated expression iba1 activation marker protein increased mnps sio2 ritc treatment transmission electron microscopy analysis revealed lysosomal accumulation mnps sio2 ritc formation vesiclelike structures mnps sio2 ritc treated bv2 cells expression several genes related metabolism inflammation altered 100 g ml mnps sio2 ritc treated microglia compared nontreated control 10 g ml mnps sio2 ritc treated microglia combined transcriptome amino acid profiling analyses revealed transport serine family amino acids including glycine cysteine serine enhanced however serine increased growth medium activated microglia especially excitotoxic dserine secretion primary rat microglia strongly enhanced activated primary microglia reduced intracellular atp levels proteasome activity cocultured neuronal cells especially primary cortical neurons via dserine secretion moreover ubiquitinated proteins accumulated inclusion bodies increased primary dopaminergic cortical neurons cocultured activated primary microglia vivo mnps sio2 ritc dserine ubiquitin aggresomes distributed mnps sio2 ritc treated mouse brainconclusionsmnps sio2 ritc induced activation microglia triggers excitotoxicity neurons via dserine secretion highlighting importance neurotoxicity mechanisms incurred nanoparticleinduced microglial activation,0.0
white matter microstructural differences children genetic risk multiple sclerosis populationbased study abstractbackgroundms patients show abnormalities white matter wm brain imaging heterogeneity location wm lesions pothole method can applied diffusionweighted images identify spatially distinct clusters divergent brain wm microstructureobjectiveto investigate association genetic risk ms spatially independent clusters decreased increased fractional anisotropy fa brain addition studied sex agerelated differencesmethods3 tesla diffusion tensor imaging dti data collected 8 12yearold children populationbased study global tractbased potholes lower fa clusters molehills higher fa clusters quantified 3047 participants usable dti data polygenic risk score prs ms calculated genotyped individuals n 1087 linear regression analyses assessed relationship prs number potholes molehills correcting multiple testing using false discovery rateresultsthe number molehills increased age potholes decreased age fewer potholes observed girls typical development msprs positively associated number molehills 09 se 029 p 0002 molehills found often corpus callosum 03 se 009 p 00003 conclusiongenetic risk ms associated spatially distinct clusters increased fa childhood brain development,0.0
ordinal sustain subtype stage inference clinical scores visual ratings ordinal data front artif intell 2021 aug 12 4613261 doi 103389 frai2021613261 ecollection 2021abstractsubtype stage inference sustain unsupervised learning algorithm uniquely enables identification subgroups individuals distinct pseudotemporal disease progression patterns crosssectional datasets sustain used identify datadriven subgroups perform patient stratification neurodegenerative diseases lung diseases continuous biomarker measurements predominantly obtained imaging however sustain algorithm currently applicable discrete ordinal data visual ratings images neuropathological ratings clinical neuropsychological test scores restricting applicability sustain narrower range settings propose ordinal sustain ordinal version sustain algorithm uses scored events model disease progression enable application sustain ordinal data demonstrate validity ordinal sustain benchmarking performance algorithm simulated data demonstrate ordinal sustain outperforms existing continuous version sustain zscore sustain discrete scored data providing much accurate subtype progression patterns better subtyping staging individuals accurate uncertainty estimates apply ordinal sustain six different subscales clinical dementia rating scale cdr using data alzheimers disease neuroimaging initiative adni study identify individuals distinct patterns functional decline using data 819 adni1 participants identified three distinct cdr subtype progression patterns independently verified using data 790 adni2 participants results provide insight patterns decline daily activities alzheimers disease mechanism stratifying individuals groups difficulties different domains ordinal sustain broadly applicable across different types ratings data including visual ratings imaging neuropathological ratings clinical behavioural ratings datapmid34458723 pmcpmc8387598 doi103389 frai2021613261,0.0
migraine multiple sclerosis patients affects functional connectivity brain circuitry involved pain processing front neurol 2021 aug 12 12690300 doi 103389 fneur2021690300 ecollection 2021abstractmigraine particularly common patients multiple sclerosis ms linked dysfunction brain circuitry modulating peripheral nociceptive stimuli using mri explored whether changes resting statefunctional connectivity rsfc may characterize occurrence migraine patients ms rsfc characteristics concerned brain regions explored 20 ms patients migraine ms+m interictal phase compared 19 ms patients without migraine msm served control group functional differences correlated frequency severity previous migraine attacks resulting impact daily activities ms+m loss periaqueductal gray matter pag positive connectivity default mode network left posterior cranial pons associated increase migraine attacks frequency contrast loss pag negative connectivity sensorimotor visual network linked migraine symptom severity related daily activities impact finally pag negative connection established prefrontal executive control network migraine ms+m patients impact daily activities underlies rsfc rearrangements brain regions involved pain perception modulationpmid34456850 pmcpmc8397382 doi103389 fneur2021690300,0.0
astrocyte heterogeneity multiple sclerosis current understanding technical challenges front cell neurosci 2021 aug 11 15726479 doi 103389 fncel2021726479 ecollection 2021abstractthe emergence single cell technologies provides opportunity characterize complex immune central nervous system cell assemblies multiple sclerosis ms study cell population structures network activation dynamics unprecedented depths review summarize current knowledge astrocyte subpopulations ms tissue discuss challenges associated resolving astrocyte heterogeneity singlenucleus rnasequencing snrnaseq discuss multiplexed imaging techniques tools defining population clusters within spatial context finally will provide outlook technologies may aid answering unresolved questions ms glial phenotypes drive ms progression neuropathological differences different clinical ms subtypespmid34456686 pmcpmc8385194 doi103389 fncel2021726479,0.0
evaluation kappa index tool diagnosis multiple sclerosis implementation routine screening procedure front neurol 2021 aug 11 12676527 doi 103389 fneur2021676527 ecollection 2021abstractmultiple sclerosis ms inflammatory demyelinating disease central nervous system previous studies shown cerebrospinal fluid csf kappa free light chains kflcs may role ms diagnosis regard kappa index kindex demonstrated higher sensitivity slightly lower specificity oligoclonal bands ocbs gold standard detection intrathecal immunoglobulin synthesis feature ms evaluated performance kindex kindex csf serum kflc divided csf serum albumin differential diagnosis ms cohort patients suspected ms kflcs quantitatively measured parallel serum csf samples turbidimetry freelite mx reagent optilite system binding site group ltd 160 634 total 252 patients kflc csf 003 mg dl sensitivity limit technique one diagnosis ms however absence ocb patient suggested synthesis intrathecal immunoglobulin globally ms patients presented significantly higher kindex levels patients without ms diagnosis 6696 vs 0025 respectively p 00001 agreement patients positive ocb testing also exhibited higher kindex levels patients negative ocb 6502 vs 0024 respectively p 00001 optimal kindex cutoff 3045 defined receiver operating characteristic roc analysis screening suspected ms achieving higher diagnostic sensitivity slightly lower specificity ocb sens 09778 spec 08629 vs sens 08889 spec 09086 respectively previously reported kindex cutoff 66 also showed good diagnostic performance sens 09333 spec 08731 validating power diagnostic biomarker ms finally time costeffective algorithm ms screening proposed offer initial rapid evaluation intrathecal immunoglobulin synthesis kflc csf kindex analysis followed reflexing ocb testing may ordered selectivelypmid34456842 pmcpmc8386692 doi103389 fneur2021676527,1.0
machine learning approaches study multiple sclerosis disease magnetic resonance images front immunol 2021 aug 11 12700582 doi 103389 fimmu2021700582 ecollection 2021abstractmultiple sclerosis ms one common autoimmune diseases commonly diagnosed monitored using magnetic resonance imaging mri combination clinical manifestations purpose review highlight main applications machine learning ml models performance ms field using mri reviewed articles last decade grouped based applications ml ms using mri data four categories 1 automated diagnosis ms 2 prediction ms disease progression 3 differentiation ms stages 4 differentiation ms similar disorderspmid34456913 pmcpmc8385534 doi103389 fimmu2021700582,0.0
progressive spastic tetraplegia axial hypotonia stahp due sod1 deficiency really new entity background amyotrophic lateral sclerosis als rare progressive fatal neurodegenerative disease due upper lower motor neuron involvement symptoms classically occurring adulthood increasing recognition juvenile presentations childhood neurodegenerative disorders caused genetic variants genes related amyotrophic lateral sclerosis main objective study detail clinical radiological neurophysiological genetic findings brazilian cohort patients recent described condition known spastic tetraplegia axial hypotonia stahp due sod1 deficiency compare cases described literature discuss whether clinical picture related sod1 protein deficiency new entity may represent earlyonset form amyotrophic lateral sclerosismethodswe conducted case series report included retrospective data five brazilian patients sod1 protein deficiency brazilian reference center neuromuscular disorders clinical data obtained review medical records descriptive statistics variables summarized using counts percentages total populationresultsall 5 patients presented childhoodonset neurodegenerative disorders characterized spastic tetraplegia axial hypotonia cases gestational history showing polyhydramnios 4 5 intrauterine growth restriction 3 5 patients patients initially presenting normal motor development six month life first year followed rapidly progressive motor decline severe dysphagia respiratory insufficiency patients accompanied cognitive impairment 3 5 patients patients homozygous c335dupg pcys112trpfs11 mutation sod1 gene completely decreased enzyme activityconclusionsthis case series biggest data collection new recent clinical entity described spastic tetraplegia axial hypotonia stahp due sod1 deficiency,0.0
chronic augmentation endocannabinoid levels persistently increases dopaminergic encoding reward cost motivation motivational deficits characterized unwillingness overcome effortful costs common feature neuropsychiatric neurologic disorders insufficiently understood treated dopamine da signaling nucleus accumbens nac facilitates goalseeking nac da release encodes motivationally salient stimuli influence effortful investment clear using fastscan cyclic voltammetry male female mice find nac da release diametrically responds cues signaling increasing cost reward da release reward unaffected cost endocannabinoid ecb signaling facilitates goal seeking nac da release investigated whether repeated augmentation ecb 2arachidonoylglycerol low dose monoacylglycerol lipase magl inhibitor facilitates motivation da signaling without development tolerance find chronic magl treatment stably facilitates goal seeking da encoding prior reward cost providing critical insight neurobiological mechanisms viable treatment motivational deficitssignificance statement decades work established fundamental role dopamine neurotransmission motivated behavior cuereward learning dopaminergic encoding cues associates motivated action remained unclear specifically dopamine neurons signal future prior reward cost whether can modified influence motivational set points known current study provides important insight dopamine neurons encode motivationally relevant stimuli influence goaldirected action supports cannabinoidbased therapies treatment motivational disorders,0.0
hla class ii polymorphisms modulate gut microbiota experimental autoimmune encephalomyelitis phenotype immunohorizons 2021 aug 11 5 8 627646 doi 104049 immunohorizons2100024abstractmultiple sclerosis ms autoimmune disease cns interaction genetic environmental factors plays important role disease pathogenesis although environmental factors account 70 disease risk exact environmental factors associated ms unknown recently gut microbiota emerged potential missing environmental factor linked pathobiology ms yet genetic factors hla class ii gene s interact gut microbiota influence ms unclear current study investigated whether hla class ii genes regulate experimental autoimmune encephalomyelitis eae ms susceptibility also influence gut microbiota previously shown hladr3 transgenic mice lacking endogenous mouse class ii genes aeko susceptible myelin proteolipid protein 91110 induced eae animal model ms whereas aekohladq8 transgenic mice resistant surprisingly hladr3dq8 double transgenic mice showed higher disease prevalence severity compared hladr3 mice gut microbiota analysis showed hladr3 hladq8 hladr3dq8 double transgenic mice microbiota compositionally different aeko mice within hla class ii transgenic mice microbiota hladq8 mice similar hladr3dq8 hladr3 presence dq8 hladr3 background increases disease severity data suggests hladq8specific microbiota may contribute disease severity hladr3dq8 mice altogether study provides evidence hladr dq genes linked specific gut microbiota contribute eae susceptibility resistance transgenic animal model mspmid34380664 doi104049 immunohorizons2100024,1.0
correction upregulation selected hervw loci multiple sclerosis correction mob dna 12 18 2021 https doiorg 101186 s13100021002431following publication original article 1 authors noticed published table 1 distorted headings columns proper ordertable 1 clinical features ms patients included studyfull size tablethe correct table 1 shown original article 1 updated,0.0
microglial inclusions neurofilament light chain release follow neuronal synuclein lesions longterm brain slice cultures background proteopathic brain lesions hallmark many agerelated neurodegenerative diseases including synucleinopathies develop least decade onset clinical symptoms thus understanding initiation propagation lesions key developing therapeutics delay halt disease progressionmethodsalphasynuclein s inclusions induced longterm murine human slice cultures seeded aggregation s seedrecognizing human antibody tested blocking seeding spreading s lesions release neurofilament light chain nfl culture medium assessedresultsto study initial stages synucleinopathies induced s inclusions murine hippocampal slice cultures seeded aggregation induction s inclusions neurons apparent early 1week postseeding followed occurrence microglial inclusions vicinity neuronal lesions 23 weeks amount s inclusions dependent type s seed cultures genetic background wildtype vs a53ts genotype formation s inclusions monitored neurofilament light chain protein release culture medium fluid biomarker neurodegeneration commonly used clinical settings local microinjection s seeds resulted spreading s inclusions neuronally connected hippocampal subregions seeding spreading inhibited s seedrecognizing human antibody applied parameters murine cultures surgical resectionderived adult human longterm neocortical slice cultures 22 61yearold donors similarly human slice cultures proofofprinciple induction s lesions achieved 1week postseeding combination viral a53ts expressionsconclusionthe successful translation brain cultures mouse human first reported induction human s lesions true adult human brain environment underlines potential model study proteopathic lesions intact mouse now even aged human brain environments,0.0
comparison iguratimod conventional cyclophosphamide sequential azathioprine treatment active lupus nephritis study protocol multicenter randomized controlled clinical trial igelu study background systemic lupus erythematosus sle autoimmune disease can involve multiple organs systems lupus nephritis ln associated high mortality morbidity however plenty patients respond present treatment relapse iguratimod igu new small molecular antirheumatic drug shown potential drug repurposing rheumatoid arthritis ra ln treatment approved treating ra northeast asia beyond expectation recent observational study 90 thirteen refractory ln patients responded iguratimod monotherapy 24 weeks steroids dose increasing medication addon entire followupmethods designthis study multicenter randomized 52week parallel positive drugcontrolled study study designed headtohead comparison iguratimod present firstline therapy ln patients total 120 patients 60 patients group enrolling plan enrolled patients assigned randomly trial control groups patients will selected six study sites china will biopsyproven active lupus nephritis first 24 weeks trial igu compared cyclophosphamide induction therapy second 24 weeks igu compared azathioprine maintenance therapy primary outcome renal remission rate including complete remission partial remission week 52 will analyzed using noninferiority hypothesis testdiscussionmost patients diagnosed sle will develop ln within 5 years ln remains major cause morbidity death sle patients although medications proven effective treatment condition least 2035 ln patients suffer relapse ineffective treatment medication intolerance also frequent trial designed demonstrate whether iguratimod can used alternative induction maintenance therapy subjects lupus nephritis data study will provide evidence whether iguratimod recommended active ln patientstrial registrationclinicaltrialsgovnct 02936375 registered october 18 2016,0.0
higher incidence sporadic renal angiomyolipoma childhood cancer survivors clin epidemiol 2021 aug 11 13707716 doi 102147 cleps317903 ecollection 2021abstractbackground cancer treatment can cause various longterm side effects including impact ultrasound findings followup childhood cancer survivors ccss often detected sporadic renal angiomyolipomas without histological confirmation samls initiated study compared occurrence saml ccss previously reported data noncancer population correlated saml cancer treatmentrelated factorsmethods cohort included 1098 ccss median age cancer diagnosis dg 43 years ultrasound followup 20142019 ccss 525 48 female 132 12 subsequent neoplasms sns 110 10 genetic syndromes ccss treated lymphomas 269 24 solid tumors 829 76 none ccss tuberous sclerosis complex tsc results saml developed 48 44 ccss 20 42 sns coincidence samls sns found ccss followup period exceeding 20 years median age saml dg 279 years interquartile range iqr 223341 median time saml dg 226 years iqr 174276 twentyone 44 ccss developed multiple bilateral samls lesions six 12 radiotherapy field saml occurrence correlated radiotherapy retroperitoneum 165fold higher 95 ci 090302 correlations cancer treatment factors female sex less clearconclusion study revealed occurrence samls ccss 10 times higher noncancer studies current characteristics ccss samls younger age bilateral multiple lesions similar tsc associated angiomyolipoma moreover observed coincidence samls sns results support hypothesis saml development ccss simply late effect therapy indicates factors involved saml developmentpmid34408499 pmcpmc8364828 doi102147 cleps317903,0.0
tdcs randomized controlled trials nostructural diseases quantitative review sci rep 2021 aug 11 11 1 16311 doi 101038 s41598021950846abstractthe increasing number quality randomized controlled trials rcts employing transcranial direct current stimulation tdcs denote rising awareness neuroscientific community electroceutical potential opening include treatments framework medical therapies indications international authorities purpose quantitative review estimate recommendation strength applying grading recommendations assessment development evaluations grade criteria pico population intervention comparison outcome model values effective tdcs treatments nostructural diseases provide estimate sham effect future rcts applying grade evaluation pathway searched literature tdcsbased rcts psychophysical diseases displaying major involvement brain electrical activity imbalances three independent authors agreed class 1 rcts 18 studies metaanalyses carried using randomeffects model pathologies subselected based pico systemic involvement criteria metaanalysis integrated extensive evidence negligible side effects lowcost easytouse procedures indicated tdcs treatments depression fatigue multiple sclerosis ranked moderately highly recommendable interventions reported pico variables left vs right dorsolateral prefrontal target 30 min 10 days depression bilateral somatosensory vs occipital target 15 min 5 days ms fatigue acrossdiseases metaanalysis devoted sham effect provided references power analysis future tdcs rcts clinical conditions highquality indications support tdcs promising tool build electroceutical treatments diseases involving neurodynamics alterationspmid34381076 doi101038 s41598021950846,0.0
glatiramer acetate enhances tumor retention innate activation immunostimulants int j pharm 2021 jun 15120812 doi 101016 jijpharm2021120812 online ahead printabstractcancer immunotherapy aims stimulate immune cells recognize attack tumor tissue immunostimulatory polyanions polyic cpg induce potent proinflammatory immune responses tlr3 tlr9 agonists respectively clinical trials tlr agonists however fraught immunerelated adverse events even injecting intratumorally effort minimize systemic exposure identified glatiramer acetate ga positivelycharged polypeptide approved multiple sclerosis delivery agent capable complexing polyic cpg reducing mobility actives small nanoparticles termed polyplexes form mixing positivelycharged ga negativelycharged immunostimulant polyic cpg ratio ga immunostimulant directly affected potency tlr activation mobility actives simulated tumor tissue polyplexes ga cpg injected intratumorally tumor model head neck squamous cell carcinoma hnscc significantly mitigated tumor growth compared vehicle controls intratumoral injections cpg showed slowest tumor growth exhibited dramatically higher systemic proinflammatory cytokine levels compared polyplexes ga cpg sequencing resected tumors revealed similar pattern upregulated proinflammatory cytokines cpg polyplexes finding supported histological tumor staining showing similar infiltration immune cells induced treatments intratumoral administration polyplexes ga immunostimulant represents translational approach enhance local immune responses mitigating systemic immunerelated adverse eventspmid34144136 doi101016 jijpharm2021120812,0.0
severe multiple sclerosis relapse covid19 vaccination case report front neurol 2021 aug 10 12721502 doi 103389 fneur2021721502 ecollection 2021abstractwe describe case acute relapse woman multiple sclerosis ms shortly mrna covid19 vaccination patient received diagnosis ms november 2016 ms centre cardarelli hospital south italy since moment clinical conditions pharmacological therapies managed ms centre according national recommendations april 2021 patient received bnt162b2 vaccine almost 48 h receiving vaccine patient developed paraesthesia weakness left arm limbs neurological examination revealed walking difficulties mri showed three new voluminous enhancing lesions received methylprednisolone iv 5 days patients neurological symptoms fully recovered along implementation covid19 vaccination programmes among vulnerable population studies needed order improve knowledge benefit risk ratio covid19 vaccinespmid34447349 pmcpmc8382847 doi103389 fneur2021721502,0.0
transcranial magnetic stimulation improves muscle involvement experimental autoimmune encephalomyelitis int j mol sci 2021 aug 10 22 16 8589 doi 103390 ijms22168589abstractskeletal muscle affected experimental autoimmune encephalomyelitis eae model multiple sclerosis produces changes including muscle atrophy histological features neurogenic involvement increased oxidative stress study aimed evaluate therapeutic effects transcranial magnetic stimulation tms involvement rat skeletal muscle compare produced natalizumab ntz eae induced injecting myelin oligodendrocyte glycoprotein mog dark agouti rats treatments ntz tms implemented day 15 day 35 clinical severity studied sacrifice soleus extensor digitorum longus muscles extracted subsequent histological biochemical analysis treatment tms ntz beneficial effect muscle involvement eae model clinical improvement functional motor deficits atrophy attenuated neurogenic muscle lesions reduced level oxidative stress biomarkers lower treatment groups compared ntz best response obtained tms parameters analyzed myoprotective effect tms higher ntz thus use tms may effective strategy reduce muscle involvement multiple sclerosispmid34445295 doi103390 ijms22168589,1.0
decoding distinctive features plasma extracellular vesicles amyotrophic lateral sclerosis background amyotrophic lateral sclerosis als multifactorial multisystem motor neuron disease currently effective treatment urgent need identify biomarkers tackle diseases complexity help early diagnosis prognosis therapy extracellular vesicles evs nanostructures released cell type body fluids biophysical biochemical characteristics vary parent cells physiological pathological state make attractive source multidimensional data patient classification stratificationmethodswe analyzed plasmaderived evs als patients n 106 controls n 96 sod1g93a tdp43q331k mouse models als purified plasma evs nickelbased isolation characterized ev size distribution morphology respectively nanotracking analysis transmission electron microscopy analyzed ev markers protein cargos western blot proteomics used machine learning techniques predict diagnosis prognosisresultsour procedure resulted highyield isolation intact polydisperse plasma evs minimal lipoprotein contamination evs plasma als patients two mouse models als distinctive size distribution lower hsp90 levels compared controls terms disease progression levels cyclophilin ev size distribution distinguished fast slow disease progressors possibly new means patient stratification immunoelectron microscopy also suggested phosphorylated tdp43 intravesicular cargo plasmaderived evsconclusionsour analysis unmasked features plasma evs als patients potential straightforward clinical application conceived innovative mathematical model based machine learning integrating ev size distribution data protein cargoes gave high prediction rates disease diagnosis prognosis,0.0
chronic white matter inflammation serum neurofilament levels multiple sclerosis neurology 2021 jun 4101212 wnl0000000000012326 doi 101212 wnl0000000000012326 online ahead printabstractobjective assess whether chronic white matter inflammation multiple sclerosis ms patients detected invivo paramagnetic rim mri lesions prl associated higher serum neurofilament light chain snfl levels marker neuroaxonal damagemethods 118 ms patients gadoliniumenhancing lesions recent relapses analyzed 3dsubmillimeter phase mri snfl levels histopathological evaluation performed 25 ms lesions 20 additional autopsy ms patientsresults univariable analyses participants 2 prl prl 2 n43 compared 1 prl prl 01 n75 higher ageadjusted snfl percentiles median 91 68 p0001 higher ms disease severity scale msss median 43 24 p0003 multivariable analyses snfl percentile levels higher prl 2 cases add 163 95 ci 46280 p001 whereas diseasemodifying treatment dmt edss t2 lesion load affect snfl similar model snfl percentile levels highest cases 4 prl n30 add 304 95 ci 156452 p001 subsequent multivariable analysis revealed prl 2 cases also higher msss add 11 95 ci 0319 p001 whereas msss affected dmt t2 lesion load histopathology chronic active smoldering lesions exhibited severe acute axonal damage lesion edge lesion center edge vs center p0004 p00002 respectively interpretation chronic white matter inflammation associated increased levels snfl disease severity nonacute ms patients suggesting prl contribute clinically relevant inflammationdriven neurodegenerationpmid34088875 doi101212 wnl0000000000012326,0.0
omega3 index fish consumption use fish oil supplements first clinical diagnosis central nervous system demyelination abstracthigher intakes omega3 polyunsaturated fatty acids n3pufas associated lower ms risk aimed test associations omega3 index blood levels n3pufas fish oil supplement use fish consumption first clinical diagnosis cns demyelination fcd cases n250 higher omega3 index compared matched group controls n471 average treatment effect ate 031 p0047 based augmented inverse probability weighting higher percentage cases controls used fish oil supplements cases17 vs controls10 found omega3 index increased time fcd study interview increased eg median 112 days based ate mean530 95 ci 508 553 median mean590 95 ci 551 630 fish oil supplement use increased similar manner median 112 days based ate proportion012 95 ci 006 018 median proportion021 95 ci 014 028 results suggest behaviour change post fcd increased use fish oil supplements,1.0
diosgenin ameliorates cellular molecular changes multiple sclerosis c57bl#x2f 6 mice abstractmultiple sclerosis ms especially known demyelinating disease central nervous system current treatments ms mostly based controlling neuroinflammation treatments promote remyelination process present diosgenin known herbal antiinflammatory antioxidant agent also shown stimulate growth myelin vitro however little evidence diosgenin effects specially myelination neuroprotection corresponding mechanisms vivo experimental autoimmune encephalomyelitis eae valid experimental model ms study therapeutic effect diosgenin clinical signs eae corresponding cellular molecular mechanisms examined emphasis myelination neuroprotection mechanisms eae induced using myelin oligodendrocyte glycoprotein mog antigen c57bl 6 mice diosgenin gavaged 100 mg kg daily onset paralysis signs half tail paralysis 18th postimmunization day treatment group blood spinal cord tissue sampling performed postimmunization day 18 lumbar spinal cord inflammation demyelination axonal degeneration assessed using hematoxylin eosin h e luxol fast blue lfb bielschowskynulls silver staining methods respectively serum spinal cord tissue level tumor necrosis factor alpha tnf tissue levels matrix metalloproteinase 9 mmp9 interleukin 17 il17 inflammatory markers microtubuleassociated proteins 1a 1b light chain 3a map1lc3a activity dependent neuroprotector homeobox adnp neuroprotective markers assayed using enzyme linked immunosorbent assay elisa method clinical score eae diosgenin treatment group significantly reduced compared eae group days 15 18 induction eae p 0001 inflammation demyelination axonal loss scores also decreased significantly diosgenin treatment group compared eae group p 005 serum spinal cord tissue level tnf tissue level mmp9 considerably decreased diosgenin treatment group comparison eae group p 001 diosgenin treatment significant effects tissue levels il17 adnp map1lc3a therefore diosgenin improved clinical signs eae lowering neuroinflammation demyelination axonal degeneration significantly affect neuroprotective factors study result diosgenin good candidate new ms treatment strategies addition antiinflammatory effects also enhance myelination,1.0
srsf1dependent inhibition c9orf72repeat rna nuclear export genomewide mechanisms neuroprotection amyotrophic lateral sclerosis background loss motor neurons amyotrophic lateral sclerosis als leads progressive paralysis death dysregulation thousands rna molecules roles multiple cellular pathways hinders identification alscausing alterations downstream changes secondary neurodegenerative process many pathological gene expression changes require therapeutic normalisation remains fundamental questionmethodshere investigated genomewide rna changes c9orf72als patientderived neurons drosophila well upon neuroprotection taking advantage gene therapy approach specifically inhibits srsf1dependent nuclear export pathological c9orf72repeat transcripts critical study evaluate overall safety efficacy partial depletion srsf1 member protein family involved gene expression ii unique opportunity identify neuroprotective rna changesresultsour study shows manipulation 362 transcripts 2257 pathological changes addition inhibiting nuclear export repeat transcripts sufficient confer neuroprotection c9orf72als patientderived neurons particular expression 90 diseasealtered transcripts fully reverted upon neuroprotection leading characterisation human c9orf72als diseasemodifying gene expression signature findings investigated vivo diseased neuroprotected drosophila transcriptomes highlighting list 21 neuroprotective changes conserved 16 human orthologues patientderived neurons also functionally validated high neuroprotective potential one diseasemodifying transcripts demonstrating inhibition alsupregulated human kcnn13 drosophila sk voltagegated potassium channel orthologs mitigates degeneration human motor neurons drosophila motor deficitsconclusionsstrikingly partial depletion srsf1 leads expression changes small proportion diseasealtered transcripts indicating rna alterations need normalization gene therapeutic approach safe preclinical models disrupt globally gene expression efficacy intervention also validated genomewide level transcripts modulated vast majority biological processes affected c9orf72als finally identification characteristic signature key rna changes modified disease state upon neuroprotection also provides potential new therapeutic targets biomarkers,1.0
perspective therapies amyotrophic lateral sclerosis can disease progression curbed abstractamyotrophic lateral sclerosis als progressive neurodegenerative disease involving upper lower motor neurons leading paralysis eventually death symptomatic treatments inhibition salivation alleviation muscle cramps relief spasticity pain still play important role enhancing quality life date riluzole edaravone two drugs approved food drug administration treatment als countries adequate consensus modest efficacy riluzole still open questions concerning efficacy edaravone slowing disease progression therefore identification novel therapeutic strategies urgently needed impaired autophagic process plays critical role als pathogenesis review focus therapies modulating autophagy context als furthermore stem cell therapies gene therapies newlydeveloped biomaterials great potentials alleviating neurodegeneration might halt disease progression review will summarize current prospective therapies als,0.0
lowfrequency stndbs provides acute gait improvements parkinsons disease doubleblinded randomised crossover feasibility trial background people parkinsons disease pd report poorer dynamic postural stability following highfrequency deep brain stimulation subthalamic nucleus stndbs may contribute increased falls risk however studies shown lowfrequency 60 hz stndbs improves clinical measures postural stability potentially providing support treatment doubleblind randomised crossover study aimed investigate effects lowfrequency stndbs compared highfrequency stimulation objective measures gait rhythmicity people pdmethodsduring high lowfrequency stndbs offmedication participants completed assessments symptom severity walking eg timed upandgo comfortable walking harmonic ratio objective measures gait rhythmicity derived head trunkmounted accelerometers provide insight dynamic postural stability lower harmonic ratios represent less rhythmic walking discriminated people pd experience falls linear mixed model analyses performed fourteen participantsresultslowfrequency stndbs significantly improved mediallateral vertical trunk rhythmicity compared highfrequency improvements independent electrode location total electrical energy delivered differences noted stimulation conditions temporal gait measures clinical mobility measures motor symptom severity presence gait retropulsionconclusionsthis study provides evidence acute benefits lowfrequency stimulation gait outcomes stndbs pd patients independent electrode location however perceived benefits therapy may diminished people experienced significant tremor preoperatively lower frequencies may cause symptoms reemergetrial registration study prospectively registered australian new zealand clinical trials registry 5 june 2018 actrn12618000944235,1.0
ongoing axonal injury chronic active lesions multiple sclerosis invivo quantification using serum neurofilament neurology 2021 jun 4101212 wnl0000000000012331 doi 101212 wnl0000000000012331 online ahead printno abstractpmid34088879 doi101212 wnl0000000000012331,0.0
multiple sclerosis incidence rate southern iran bayesian epidemiological study background multiple sclerosis ms remains public health challenge due unknown biological mechanisms clinical impacts young people prevalence disease iran reported 530 7428 per 100 000person high prevalence disease fars province purpose study assess spatial pattern ms incidence rate modeling associations s spatial dependence neighboring regions risk factors bayesian poisson model can lead improvement health resource allocation decisionsmethoddata 5468 patients diagnosed ms collected according mcdonalds criteria new cases ms reported ms society fars province 1991 2016 association percentage people low vitamin d intake smoking abnormal bmi alcohol consumption addition spatial structure bayesian spatiotemporal hierarchical model used determine relative risk trend ms incidence rate 29 counties fars provinceresultscountylevel crude incidence rates ranged 022 1131 cases per 100 000person population highest relative risk estimated 180 county shiraz capital fars province lowest relative risk estimated 011 zarindasht county southern fars percentages vitamin d supplementation intake smoking significantly associated incidence rate ms results showed 1 increase vitamin d supplementation intake associated 2 decrease risk ms 1 increase smoking associated 16 increase risk msconclusionbayesian spatiotemporal analysis ms incidence rate revealed trend south south east fars province less steep mean trend disease lower incidence rate associated higher percentage vitamin d supplementation intake lower percentage smoking previous studies also shown smoking low vitamin d among covariates risk factors might associated high incidence ms,0.0
ifp35 family proteins promote neuroinflammation multiple sclerosis proc natl acad sci u s 2021 aug 10 118 32 e2102642118 doi 101073 pnas2102642118abstractexcessive activation t cells microglia represents hallmark pathogenesis human multiple sclerosis ms however regulatory molecules overactivating immune cells remain identified previously reported extracellular ifp35 family proteins including ifp35 nmi activated macrophages proinflammatory molecules periphery investigated functions process neuroinflammation central nervous system cns periphery analysis clinical transcriptomic data showed expression ifp35 family proteins upregulated patients ms additional vitro studies demonstrated ifp35 nmi released multiple cells ifp35 nmi subsequently triggered nuclear factor kappa bdependent activation microglia via tlr4 pathway importantly showed ifp35 nmi activated dendritic cells promoted nave t cell differentiation th1 th17 cells nmi ifp35 administration neutralizing antibodies ifp35 alleviated immune cells infiltration demyelination cns thus reducing severity experimental autoimmune encephalomyelitis together findings reveal hitherto unknown mechanism ifp35 family proteins facilitate overactivation t cells microglia propose avenues study pathogenesis mspmid34362845 doi101073 pnas2102642118,1.0
ms remyelinating drug bexarotene rxr agonist promotes induction human tregs suppresses th17 differentiation vitro front immunol 2021 aug 10 12712241 doi 103389 fimmu2021712241 ecollection 2021abstractthe retinoid x receptor agonist bexarotene promotes remyelination patients multiple sclerosis murine studies also demonstrated rxr agonists antiinflammatory effects enhancing ability alltransretinoic acid atra promote tregulatory cell treg induction reduce th17 differentiation vitro stimulating human nave cd4 tcells presence treg th17 skewing cytokines show bexarotene also tips human treg th17 axis favor treg induction unlike murine cells occurs independently atra retinoic acid receptor signaling tregs induced presence bexarotene express canonical markers tregulation functionally suppressive vitro circulating treg numbers increase blood trial patients receiving bexarotene believe treg induction likely occur within tissues findings lend support developing rxr agonists treatments autoimmune diseases particular multiple sclerosispmid34447379 pmcpmc8382874 doi103389 fimmu2021712241,1.0
inflammatory pseudotumor castleman disease igg4related disease masquerading kidney malignancy background widespread clinical application imaging techniques renal spaceoccupying lesions identified increasing frequency report two rare cases castleman disease cd igg4related disease igg4rd presenting primarily symptoms imaging findings kidney malignancycase presentationin case 1 occupying lesion located right renal pelvis detected using magnetic resonance imaging 32yearold female presented hematuria lumbago first misdiagnosed carcinoma renal pelvis patient underwent right radical nephroureterectomy however postoperative pathological immunohistochemistry studies finally confirmed diagnosis cd case 2 45yearold male presented chief complaint anuria nephrostomy renal biopsy indicated lymphoma following antegrade urography computed tomography urography performed revealed bilateral hydronephrosis mass lesions around renal pelvis partial resection masses frozen section examination indicated diagnosis cd however results postoperative histopathology immunohistochemistry combined serum igg4 consistent igg4rd patients recovered well drug treatment without recurrence diseasesconclusionsinflammatory pseudotumor cd igg4rd kidney involvement primarily diagnosed postoperative histopathology can pose preoperative diagnostic challenge lesions can masquerade kidney malignancy therefore recommend core biopsy nonnegligible procedure evaluate renal masses potentially prevent unnecessary surgical treatment,0.0
association gray matter atrophy patterns clinical phenotype progression multiple sclerosis neurology 2021 apr 23101212 wnl0000000000012021 doi 101212 wnl0000000000012021 online ahead printno abstractpmid33893208 doi101212 wnl0000000000012021,0.0
fractalkine signaling regulates oligodendroglial cell genesis svz precursor cells stem cell reports 2021 jun 30s22136711 21 003167 doi 101016 jstemcr202106010 online ahead printabstractneural oligodendrocyte precursor cells npcs opcs subventricular zone svz brain contribute oligodendrogenesis throughout life part due direct regulation chemokines role chemokine fractalkine well established microglia however effect fractalkine svz precursor cells unknown show murine svz npcs opcs express fractalkine receptor cx3cr1 bind fractalkine exogenous fractalkine directly enhances opc oligodendrocyte genesis svz npcs vitro infusion fractalkine lateral ventricle adult npc lineagetracing mice leads increased newborn opc oligodendrocyte formation vivo also show opcs secrete fractalkine inhibition endogenous fractalkine signaling reduces oligodendrocyte formation vitro finally show fractalkine signaling regulates oligodendrogenesis cerebellar slices ex vivo summary demonstrate novel role fractalkine signaling regulating oligodendrocyte genesis postnatal cns precursor cellspmid34270934 doi101016 jstemcr202106010,0.0
remyelination trials expecting unexpected neurol neuroimmunol neuroinflamm 2021 aug 10 8 6 e1066 doi 101212 nxi0000000000001066 print 2021 novabstractneuroaxonal loss believed underpin progressive disability characterizes multiple sclerosis ms focal inflammatory demyelination principal cause acute axonal transection subsequent axonal degeneration gradual attrition permanently demyelinated axons may also contribute tissue damage particularly progressive phase disease therefore remyelination considered putative neuroprotective strategy article review potential pitfalls remyelination trials provide framework appropriate design temper expectations times unrealistic researchers regulators pharmaceutical industrypmid34376551 doi101212 nxi0000000000001066,1.0
abnormalities normalappearing white matter multiple sclerosis lesions arise brain commun 2021 aug 10 3 3 fcab176 doi 101093 braincomms fcab176 ecollection 2021abstractnormalappearing white matter far normal multiple sclerosis little known precise pathology spatial pattern alteration relation subsequent lesion formation study undertaken evaluate normalappearing white matter abnormalities brain areas multiple sclerosis lesions subsequently form investigate spatial distribution normalappearing white matter abnormalities persons multiple sclerosis brain mris prelesion normalappearing white matter analysed participants new t2 lesions pooled three clinical trials synergy nct01864148 n 85 relapsing multiple sclerosis test data set ascend nct01416181 n 154 secondary progressive multiple sclerosis advance nct00906399 n 261 relapsingremitting multiple sclerosis used validation data sets focal normalappearing white matter tissue state analysed prior lesion formation areas new t2 lesions later formed prelesion normalappearing white matter using normalized magnetization transfer ratio t2weighted nt2 intensities compared overall normalappearing white matter spatially matched contralateral normalappearing white matter outcome analysed using linear mixedeffects models followup time categorical variable patientlevel characteristics including treatment group baseline variables treated fixed effects synergy nt2 intensity significantly higher normalized magnetization transfer ratio lower prelesion normalappearing white matter versus overall contralateral normalappearing white matter time points 24 weeks new t2 lesion onset ascend advance normalized magnetization transfer ratio available nt2 intensity prelesion normalappearing white matter significantly higher compared overall contralateral normalappearing white matter prelesion time points extending 2 years prior lesion formation trials nt2 intensity contralateral normalappearing white matter also significantly higher prelesion time points compared overall normalappearing white matter brain atlases normalappearing white matter abnormalities generated using measures voxelwise differences normalized magnetization transfer ratio normalappearing white matter persons multiple sclerosis compared scannermatched healthy controls observed overall spatial distribution normalappearing white matter abnormalities persons multiple sclerosis largely recapitulated anatomical distribution probabilities t2 hyperintense lesions overall findings suggest intrinsic spatial properties longstanding precursory abnormalities normalappearing white matter tissue may contribute risk autoimmune acute demyelination multiple sclerosispmid34557664 pmcpmc8453433 doi101093 braincomms fcab176,1.0
modern technology multishell diffusion mri reveals diffuse white matter changes young adults relapsingremitting multiple sclerosis front neurosci 2021 aug 10 15665017 doi 103389 fnins2021665017 ecollection 2021abstractobjective characterize microstructural white matter changes related relapsingremitting multiple sclerosis using advanced diffusion mri modeling tractography association imaging data patients cognitive performance fatigue severity depressive symptoms also exploredmethods crosssectional study 24 relapsingremitting multiple sclerosis patients 11 healthy controls compared using high angular resolution diffusion imaging hardi imaging method includes multishell scheme free water correction obtain tissuespecific measurements probabilistic tracking algorithm robust crossing fibers white matter lesions automatic streamlines bundle dissection tractprofiling tractometry neuropsychological evaluation included symbol digit modalities test paced auditory serial addition test modified fatigue impact scale beck depression inventoryiiresults bundlewise analysis tractometry revealed difference patients controls 11 14 preselected white matter bundles patients free water corrected fractional anisotropy significantly reduced radial mean diffusivities increased consistent diffuse demyelination fornix left inferior frontooccipital fasciculus exhibited higher free water fraction eight bundles showed increase total apparent fiber density four bundles higher number fiber orientations suggesting axonal swelling increased organization complexity respectively association study depressive symptoms associated diffusion abnormalities right superior longitudinal fasciculusconclusion tissuespecific diffusion measures showed abnormalities along multiple cerebral white matter bundles patients relapsingremitting multiple sclerosis proposed methodology combines freewater imaging advanced bundle dissection tractometry novel approach investigate cerebral pathology multiple sclerosis opens new window use hardiderived measures free water corrected diffusion measures advanced diffusion mri provides better insight cerebral white matter changes relapsingremitting multiple sclerosis namely diffuse demyelination edema increased fiber density complexitypmid34447292 pmcpmc8383891 doi103389 fnins2021665017,1.0
significance homeodomain transcription factor 2 colon cancer cells background colon cancer serious malignant tumor reported pairedlike homeodomain transcription factor 2 pitx2 can promote progression several types cancer via regulating wnt catenin pathway also demonstrated high levels long noncoding rna lncrna gastric carcinoma high expressed transcript 1 ghet1 can also promote development cervical cancer via activating wnt catenin pathway however whether pitx2 can affect development colon cancer via regulating expression lncrna ghet1 remains unclearresultsthe results demonstrated pitx2 knockdown attenuated proliferation migration invasion abilities colon cancer cells additionally pitx2 promoted expression lncrna ghet1 via binding promoter overexpression lncrna ghet1 induced expression wnt catenin signalingrelated proteins cyclin d1 cmyc mmp7 furthermore lncrna ghet1 overexpression abrogated pitx2 silencingmediated decreased proliferation migration invasion abilities colon cancer cellsconclusionthe findings present study suggested pitx2 enhance proliferation migration invasion abilities colon cancer cells via upregulating lncrna ghet1 activating wnt catenin pathway,0.0
study design minimum data set covid19 registry system background beginning covid19 pandemic development infrastructures record collect report covid19 data become fundamental necessity world disease registry system can help build infrastructure collect data systematically study aimed design minimum data set covid19 registry systemmethodsa qualitative study design mds covid19 registry system performed five phases ahvaz university medical sciences khuzestan province southwestern iran 20202021 first phase assessing information requirements performed covid19 registry system data elements identified second phase third phase mds selected four phases covid19 registry system implemented pilot study test mds finally based experiences gained covid19 registry system implementation mds evaluated corrections maderesultsmds covid19 registry system contains eight top groups including administrative 34 data elements disease exposure 61 data elements medical history physical examination 138 data elements findings clinical diagnostic tests 101 data elements disease progress outcome treatment 55 data elements medical diagnosis cause death 12 data elements followup 14 data elements covid19 vaccination 19 data elements data respectivelyconclusioncreating standard comprehensive mds can help design national data dictionary covid19 improve quality covid19 data,0.0
thegold coast criteria increases diagnostic sensitivity amyotrophic lateral sclerosis chinese population abstractobjectivesthe aim study assess compare diagnostic utility new diagnostic criteria amyotrophic lateral sclerosis als abbreviated gold coast criteria revised el escorial reec awaji criteriamethodsclinical electrophysiological data 1185 patients january 2014 december 2019 peking union medical college hospital als database reviewed sensitivity gold coast criteria compared possible reec awaji criteria defined proportion patients categorized definite probable possible als resultsa final diagnosis als recorded 1162 patients sensitivity gold coast criteria 966 95 confidence interval ci 953975 greater reec 851 95ci 829871 awaji 853 95ci 832873 addition sensitivity novel criteria maintained robust across subgroups advantage prominent limbonset als patients completed electromyographic tests achieve reec diagnostic categories sensitivity gold coast criteria 844conclusionsthe current study demonstrated gold coast criteria exhibited greater diagnostic sensitivity reec awaji criteria chinese als population application gold coast criteria considered clinical practice future therapeutic trials,0.0
ponesimod ponvory multiple sclerosis med lett drugs ther 2021 aug 9 63 1630 123125no abstractpmid34550110,0.0
characterization etv6ntrk3 rearrangement unusual highly significant fish signal pattern secretory carcinoma salivary gland case report background fusions neurotrophic tropomyosin receptor kinase genes ntrk1 ntrk2 ntrk3 various partner genes occur common rare tumours paramount predictive value due availability effective pantrk inhibitors like larotrectinib entrectinib detection ntrk fusions mainly performed fluorescence situ hybridization fish next generation sequencing ngs case described showed unusual highly significant fish signal pattern ntrk3 break apart probe indicative functional ntrk3 rearrangementcase presentationwe describe case male patient originally diagnosed adenocarcinoma parotid gland without evidence metastases development multiple lung metastases extensive immunohistochemical molecular examination archived tumour tissue including analysis ntrk performed ntrk expression detected immunohistochemistry ihc comprehensively analysed fish quantitative reverse transcription pcr rtqpcr ngs ntrk3 break apart fish showed multiple faint single 3 signals addition fusion signals quantitative reverse transcription pcr ngs confirmed etv6exon5ntrk3exon15 fusion diagnosis therefore revised metastatic secretory carcinoma salivary gland patient subsequently treated larotrectinib resulting persisting partial remissionconclusionsour findings underline importance aware noncanonical signal patterns fish analysis detection ntrk rearrangements faint single 3 signals can indicate functional ntrk rearrangement therefore high predictive value,0.0
rare disease patientreported outcome measure revision validation german version systemic sclerosis quality life questionnaire sscqol using rasch model background rare disease patientreported outcome measures proms require linguistic adaptation overcome challenge geographically dispersed patient populations importantly proms healthrelated quality life hrqol accurately capture responses patientidentified concerns systemic sclerosis quality life questionnaire sscqol 29item tool validated six languages previous evaluation german version revealed problems dichotomous responses study aimed revise german sscqol extend response structure evaluate content construct validity reliability unidimensionalitymethodsthe instrument validation study involved revising german sscqol response structure cognitive debriefing patients validation using rasch analysis revised sscqol completed swissgermanspeaking patients ssc within swiss management systemic sclerosis manoss study rasch analysis employed test validity reliability unidimensionality revised instrumentresultsbased cognitive debriefing patients n 6 dichotomous items extended polytomous 4point response structure total 78 patients completed revised sscqol initial analysis 29 items suggested scale lacked fit model 2 51224 df 29 p 0007 grouping items five domains resulted adequate fit rasch model 2 5343 df 5 p 0376 unidimensionality proportion significant independent t tests 0045 95 ci 00160114 overall scale well targeted high internal consistency person separation index psi 0931 worked consistently patients different demographic clinical characteristicsconclusionsthe revised german sscqol 4point response structure valid reliable measure rasch analysis useful validating continuous response structure quality life measures evaluation measurement equivalence germanspeaking cultures required multinational comparisons data pooling,0.0
genetic susceptibility multiple sclerosis african americans plos one 2021 aug 9 16 8 e0254945 doi 101371 journalpone0254945 ecollection 2021abstractobjective explore nature geneticsusceptibility multiple sclerosis ms africanamericansbackground recently number geneticassociations ms exploded although msassociations specific haplotypes within major histocompatibility complex mhc known decades example haplotypes hladrb11501hladqb10602 hladrb10301 hladqb10201 odds ratios ors msassociation orders magnitude stronger many newlydiscovered associations nevertheless haplotypes part much larger conserved extended haplotypes cehs span class class ii mhc regions africanamericans greater risk developing ms compared native africans lesser risk compared europeans purpose manuscript explore relationship mssusceptibility ceh makeup africanamerican cohortdesign methods africanamerican aa cohort consisted 1 305 patients ms 1 155 controls selfidentified africanamerican comparison used 18 492 controls 11 144 mscases predominantly european wellcome trust case control consortium wtccc 28 557 phased native africans multinational match registry wtccc africanamericans phased five hla loci hlaa hlac hlab hladrb1 hladqb1 11 snps 10 noncoding regions surrounding class ii region drb1 gene using previouslypublished probabilistic phasing algorithmsresults 32 frequent cehs 18 56 occurred either frequently exclusively africans whereas 9 28 occurred frequently exclusively europeans remaining 5 cehs occurred neither control group although likely african origin eight cehs carried drb11503dqb10602a36 haplotype three carried drb11501dqb10602a1 haplotype african americans singlecopy european ceh 0301_0702_0702_1501_0602_a1 associated considerable msrisk 330 p 00001 similar observed wtccc 325 p10168 contrast msrisk european ceh 0201_0702_0702_1501_0602_a1 less 149 ns similar wtccc 22 p1038 moreover four african haplotypes protective relative neutral reference three european cehs also five african cehsconclusions common cehs african americans divisible either african european origin derived without modification source population european cehs linked msrisk general similar impacts africanamericans europeans contrast african cehs mixed msrisks msrisk exceeded neutralreference group whereas many others cehs protectiveperhaps providing partial rationale lower msrisk africanamericans compared europeanamericanspmid34370753 doi101371 journalpone0254945,0.0
factors associated igg levels adults igg subclass deficiency background factors associated igg levels adults igg subclass deficiency iggsd incompletely understood studied adults iggsd subnormal igg1 subnormal igg1 igg3 subnormal igg3 without subnormal igg subclasses iga igm compiled age sex autoimmune condition s ac atopy igg igg subclasses iga igm iggsum igg1 + igg2 + igg3 + igg4 d percentage difference iggsum igg compared attributes patients without subnormal igg 700 g l subnormal igg1 subclass groups analyzed iggsum igg relationships performed backward stepwise regressions igg using independent variables igg subclasses age sex d using independent variables age sexresultsthere 39 patients subnormal igg1 897 women 53 subnormal igg1 igg3 887 women 115 subnormal igg3 913 women fifteen patients 385 32 patients 604 respective subnormal igg1 subclass groups subnormal igg attributes patients without igg 700 g l similar except ac prevalence lower patients subnormal igg1 igg 700 g l 700 g l p 00484 mean median igg1 igg2 significantly lower patients igg 700 g l subnormal igg1 subclass groups p 00001 comparisons regressions igg three subclass groups revealed positive associations igg1 igg2 p 00001 association regressions d revealed significant association igg1 percentages iggsum lower igg2 percentages higher patients subnormal igg1 subclass levels subnormal igg3 p 00001 comparisons conclusionswe conclude igg1 igg2 major determinants igg patients subnormal igg1 combined subnormal igg1 igg3 subnormal igg3 patients subnormal igg1 combined subnormal igg1 igg3 median igg2 levels significantly lower igg 700 g l igg 700 g l,0.0
clinical decision support system rhina diagnosis treatment acute chronic rhinosinusitis background rhinosinusitis inflammation sinonasal cavity affects roughly one seven people per year acute rhinosinusitis ars mostly apart allergic etiology caused viral infection cases 3050 bacterial superinfection antibiotics indicated rare cases according epos guidelines nevertheless prescribed 80 ars cases increases resistant bacterial strains populationmethodswe designed clinical decision support system cdss rhina based web application created html 5 using javascript jquery ccs3 php scripting language presented cdss rhina helps general physicians decide whether prescribe antibiotics patients rhinosinusitisresultsin retrospective study total 1465 patients rhinosinusitis cdss rhina presented 902 consistency diagnosis treatment made ent specialistconclusionpatients assessed assistance cdss rhina decrease overprescription antibiotics turn help reduce bacterial resistance commonly prescribed antibiotics,0.0
prognostic accuracy neda3 longterm outcomes multiple sclerosis neurol neuroimmunol neuroinflamm 2021 aug 9 8 6 e1059 doi 101212 nxi0000000000001059 print 2021 novabstractbackground objectives estimate proportions patients relapsingremitting multiple sclerosis despite achieving evidence disease activity3 neda3 status first 2 treatment years experienced relapseassociated worsening raw progression independent relapse activity pira following yearsmethods selected patients neda3defined relapse disability worsening mri activityin first 2 years either glatiramer acetate interferon beta initial treatment estimated longterm probability subsequent raw pira considered 2 contrasting outcomes cumulative incidence functions competing risk regressions used identify baseline ie treatment start predictors raw piraresults 687 patients 224 326 neda3 first 2 treatment years median followup time 12 years treatment start 58 patients 26 experienced disability accrual 31 14 raw 27 12 pira raw predicted presence 9 t2 lesions subdistribution hazard ratio shr 392 p 0012 contrastenhancing lesions shr 238 p 0047 baseline mri scan either temporary permanent discontinuation initial treatment shr 111 p 0015 pira predicted advancing age shr 105 p 0036 year increase presence 1 spinal cord lesion baseline mri scan shr 408 p 0016 discussion adoption neda3 criteria led prognostic misclassification 1 4 patients different risk factors associated raw pira suggesting alternative mechanisms disability accrualclassification evidence study provides class ii evidence patients rrms attained neda3 status subsequent raw associated baseline mri activity discontinuation treatment pira associated age presence baseline spinal cord lesionspmid34373345 doi101212 nxi0000000000001059,0.0
clinical course neurogenic bladder dysfunction human tcell leukemia virus type1associated myelopathy tropical spastic paraparesis nationwide registry study japan background patients human tcell leukemia virus type 1associated myelopathy tropical spastic paraparesis ham tsp develop neurogenic bladder dysfunction however longitudinal changes treatment effects remain poorly understood study aimed characterize clinical course urinary dysfunction populationmethodsthis prospective observational study included 547 patients enrolled hamnet nationwide registry ham tsp japan urinary dysfunction severity evaluated using ham tspbladder dysfunction symptom score hambdss ham tspbladder dysfunction severity grade hambdsg specific measures recently developed assessing urinary dysfunction ham tsp analyzed longitudinal changes 6year followup period associations urinary gait dysfunction treatment efficacy urinary catheterization mirabegron 3adrenergic agonist overactive bladder symptoms resultsthe mean standard deviation sd age disease duration enrollment 619 107 years 166 116 years respectively 746 patients women 80 free urinary symptoms hambdsg 0 654 urinary symptoms medication hambdsg 232 33 used intermittent indwelling catheters hambdsg ii iii respectively hambdsg bdss worse patients greater gait dysfunction p 0001 6year followup 667 patients hambdsg 0 developed new urinary symptoms hambdsg enrollment 108 started using urinary catheters importantly hambdss significantly improved initiating catheterization mean sd change 893 1078 p 0001 number patients receiving mirabegron increased fourth year multivariable linear regression analysis significantly associated mirabegron improvement hambdss 582 95 confidence interval 913 251 p 0001 conclusionsurinary dysfunction affected 92 patients progressed 6year followup urinary symptoms severe patients poorer gait function urinary catheterization mirabegron effective relieving symptoms effective utilization realworld data key establishing evidence rare diseases ham tsp,0.0
brainheart link case report critically located multiple sclerosis lesion brainstem leading recurrent takotsubo syndrome front cardiovasc med 2021 aug 9 8674118 doi 103389 fcvm2021674118 ecollection 2021abstractvarious central nervous system cns diseases including neurovascular neuroinflammatory diseases can lead stress cardiomyopathy also known takotsubo syndrome tts present case 69yearold woman cardiovascular comorbidities suffering repeated episodes tts respiratory failure due critical lesion brainstem leading diagnosis multiple sclerosis ms despite aggressive treatment intractable recurrent symptoms patient occurred repeated bouts autonomic dysfunction respiratory failure ultimately led installment palliative care patient passing away tts raise suspicion underlying neurological diseases thorough questioning previous neurological symptoms extensive neurological workup warranted ms considered trigger tts also elderly patients cardiovascular risk factorspmid34434971 pmcpmc8381246 doi103389 fcvm2021674118,0.0
impact remoteness patient outcomes people multiple sclerosis australia abstractbackgroundlittle known whether living remote areas associated worse health outcomes australians msobjectivesto evaluate whether living remote areas associated worse health outcomes employment outcomes different disease modifying therapy dmts utilisation among australians msmethodswe included 1 611 participants australian ms longitudinal study level remoteness major cities inner regional outer regional remote remote australia determined using postcode data analysed using linear logbinomial logmultinomial negative binomial regressionresultsliving remote areas associated substantial worse health employment outcomes consistent pattern living inner regional areas worse outcomes effect sizes relatively small clear doseresponse relationships increasing remoteness living remote areas less likely use high efficacy dmts adjusting age disease duration education level marginally reduced associationsconclusionsthere large inequity health outcomes australian ms population due remoteness however modest consistent differences health outcomes dmts treatment likely substantial cumulative impact individual level,0.0
increasing tolllike receptor 2 astrocytes induced schwann cellderived exosomes promotes recovery inhibiting cspgs deposition spinal cord injury background traumatic spinal cord injury sci severely disabling disease leads loss sensation motor autonomic function exosomes great potential diagnosis prognosis treatment sci ability easily cross bloodbrain barrier function schwann cellderived exosomes scdes still largely unknownmethodsa t10 spinal cord contusion established adult female mice scdes injected tail veins mice three times week 4 weeks induction sci control group injected pbs highresolution transmission electron microscope western blot used characterize scdes tolllike receptor 2 tlr2 expression astrocytes chondroitin sulfate proteoglycans cspgs deposition neurological function recovery measured spinal cord tissues group immunofluorescence staining tlr2 gfap cs56 5ht iiitublin respectively tlr2f f mice crossed gfapcre strain generate astrocyte specific tlr2 knockout mice tlr2 finally western blot analysis used determine expression signaling proteins ikk inhibitor sc514 used validate involved signaling pathwayresultshere found tlr2 increased significantly astrocytes postsci scdes treatment can promote functional recovery induce expression tlr2 astrocytes accompanied decreased cspgs deposition specific knockout tlr2 astrocytes abolished decreasing cspgs deposition neurological functional recovery postsci addition signaling pathway nfb pi3k involved tlr2 activation validated western blot furthermore ikk inhibitor sc514 also used validate signaling pathwayconclusionthus results uncovered scdes can promote functional recovery mice postsci decreasing cspgs deposition via increasing tlr2 expression astrocytes nfb pi3k signaling pathway,0.0
clinical presentation causes nontraumatic spinal cord injury observational study emergency patients front neurol 2021 aug 9 12701927 doi 103389 fneur2021701927 ecollection 2021abstractintroduction diagnosing nontraumatic spinal cord injury ntsci often challenging however clear discrimination nonspinal pathologies eg myelopathymimics mms critical preventing longterm disability death retrospective study 1 investigated causes ntsci 2 identified clinical markers associated ntsci 3 discuss implications ntsci management methods sample consisted 5913 consecutive neurological neurosurgical patients treated emergency department oneyear period patients new worsened bilateral sensorimotor deficit defined possible ntsci compared clinical imaging findings allocated patients ntscis mms results ninetythree included cases thirtysix 387 diagnosed ntsci fiftytwo patients 559 classified mms five patients 54 underlying pathology remained unclear predominant causes ntsci spinal metastases 333 inflammatory disorders 222 degenerative pathologies 194 586 ntsci patients required emergency treatment presence sensory level p 0001 sphincter dysfunction p 002 significant discriminators ntsci mms conclusion study onethird patients presenting new bilateral sensorimotor deficit ntsci majority required emergency treatment since significant clinical overlap nonspinal disorders standardized diagnostic workup including routine spinal mri recommended ntsci management rather approach mainly based clinical findingspmid34434162 pmcpmc8380771 doi103389 fneur2021701927,0.0
incidence cancer multiple sclerosis treatment era registry based cohort study abstractbackgroundwhether diseasemodifying therapies dmts influence cancer multiple sclerosis ms uncertainobjectivesassess incidence cancer diagnosis among norwegian ms patients compared general population 1953 1995 1996 2017reflecting era introduction dmtsmethodswe performed nationwide cohort study comprising 6949 ms patients 37 922 controls matched age sex county cohort linked norwegian cancer registry cause death registry national educational database used poisson regression calculate incidence rate ratio irr cancerresultsduring 19531995 ms patients similar cancer frequency compared controls irr 111 95 confidence intervals ci 090137 although ms patients increased frequency cancer endocrine glands irr 251 127493 19962017 identified significant increased frequency cancer among ms patients compared controls irr 138 95 ci 128152 brain irr 197 141278 meninges irr 244 154377 respiratory organs irr 196 149263 excess cancer diagnosis frequent among ms patients60 years age hr 130 115147 conclusionincidence cancer among ms patients compared controls higher 1996 2017 corresponding time introduction dmt ms observed frequently among ms patients older 60 years age,0.0
possible markers venous sinus pressure elevation multiple sclerosis correlations gender disease progression abstractbackgroundin previous study multiple sclerosis ms found associated increase intracranial arterial pulsation volume reduction venous sinus compliance affecting pulsation dampening suggestion reduction compliance sagittal sinus ms caused increase venous pressure secondary transverse sinus stenosis differences noted depending gender patients however original study relatively underpowered subclassification purpose current study enroll larger number patients allow subclassification gender disease type evaluate markers possible venous pressure alterationmethods103 patients ms prospectively recruited ms clinic compared 50 matched nonms patients using 3dt1 post contrast images sagittal sinus crosssectional area measured narrowest portion transverse sinuses located cross sectional areas wetted circumferences measured calculate minimum hydraulic effective diameters jugular bulb heights measured voxel wise brain morphometry performed evaluate atrophy statistical analysis performed using nonparametric methods assessed using 005resultscompared controls ms patientsnull sagittal sinuses 23 larger crosssection p00001 transverse sinuses average effective stenosis 39 area p00001 62 increase jugular bulb height p00001 ms patients showed reduction normalized grey matter volume 28 p 00001 males ms showed worse outcomes compared females increased edss grey matter loss 23 larger sagittal sinus area p002 22 higher jugular bulb height p003 lower transverse sinus stenosis percentage 19 vs 48 p00001 progressive forms ms also worse outcomes 19 larger sagittal sinus area p004 compared relapsing remitting msconclusionin larger cohort worse outcomes males progressive forms ms associated larger sagittal sinuses possible cause altered sinus pressure females narrower transverse sinuses males higher jugular bulbs may associated increased venous sinus pressure,0.0
demographic clinical symptomatic correlates subjective sleep quality adults multiple sclerosis abstractbackgroundthis study examined comprehensive set demographic clinical symptomatic variables correlates subjective sleep quality adults multiple sclerosis ms methodsparticipants ms n485 completed pittsburgh sleep quality index psqi demographics clinical characteristics questionnaire patient determined disease steps scale pdds fatigue severity scale hospital anxiety depression scale conducted bivariate spearmannulls rho correlation analyses multiple linear regression analysis identifying variables associated psqi scoresresultsparticipants mean standard deviation age 554 126 years mostly female 78 median interquartile range pdds 20 30 higher levels fatigue 032 symptoms anxiety 039 depression 036 younger age 012 lower income status 013 shorter ms disease duration 011 minority group 009 unemployed 010 associated worse sleep quality significant associations gender marital status parental status education level disability status ms disease type sleep quality overall regression model accounted 263 variance sleep quality f 8 2298 2025 significant coefficients anxiety 025 fatigue 018 depression 016 employment status 012 disease duration age race income leveldiscussionparticipants higher levels anxiety fatigue depression unemployed reported worse sleep quality sample adults ms results may identify specific subgroups ms population experience sleep problems therefore greatest need interventions designed improve sleep impairment,0.0
combined training improves expression profile inflammationassociated antimicrobial peptides micrornas tlr4 patients multiple sclerosis iran j allergy asthma immunol 2021 aug 7 20 4 441452abstractsome antimicrobial peptides amps micrornas mirs tolllike receptor 4 tlr4 involved autoimmune diseases may affected exercise training purpose study investigate effect eightweek combined exercise training aerobic resistance expression inflammatory factors including human betadefensin2 hbd2 cathelicidin ll37 tlr4 mir23b mir155 mir326 women relapsing remitting multiple sclerosis rrms investigated yet twentythree women 2040 years rrms randomized combined training ct control con groups ct group subjects completed eight weeks supervised ct using treadmill stationary bicycle aerobic exercise weight machines resistance exercise expression levels hbd2 ll37 tlr4 mir23b mir155 mir326 measured realtime polymerase chain reaction rtpcr baseline end study although expression hbd2 mir23b decreased ct con groups reduction lower ct group con group p0001 expression ll37 ct group remained unchanged con group increased thus betweengroup difference significant although tlr4 mir155 mir326 expression increased groups compared baseline increase ct group lower con group results showed combined training might improve inflammatory symptoms affecting expression amps mirs tlr4 patients relapsing remitting multiple sclerosispmid34418898,0.0
multiple sclerosis therapy consensus group mstcg answers discussion questions question 1 diseasemodifying immunotherapy initiated onset disability already cis eg isolated optic neuritis explicit goal multiple sclerosis ms therapy best possible disease control including best possible quality life patient option use highly effective therapeutics early early possible response disease activity specifically appropriate diseasemodifying therapy dmt selected based individual patient incorporates situation prognostic analysis includes disease activity disease severity balancing therapy safety risks considering patients age gender living situation perspective mstcg multiple sclerosis therapy consensus group supported several large observational registry studies modern ms therapy can prevent accumulation disability thus possible neurodegenerationthe mstcg recommends classifying ms mild moderate active highly active see fig 1 classification based relapse frequency ii mri findings lesion load lesion localization iii regression relapse s disease activity disease severity measured clinical well radiological parameters also patients age comorbidities considered activity determined based clinical relapses severity clinical symptoms duration tendency regress mri activity contrastenhancing lesions new enlarged t2 lesions progression determined annual frequent examination including careful clinical assessment addition edss standardized instruments assessing clinical function patients ms include multiple sclerosis functional composite msfc brief international cognitive assessment ms bicams 6 2min walk tests timed 25ft walk test notably ms classifications categorical rigid require continuous review close followupfig 1figure1diseasemodifying therapy ms 1 azathioprine formally approved rarely applied 2nd choice 2 mitoxantrone formally approved well highly active rrms rarely applied due unfavorable side effect profile cumulative maximum dose 2nd choice 3 natalizumab iv sc especially case hpyv2 jcv antibody positivity hpyv2 jcv ab 09 hpyv2 jcv ab titer risk stratification essential due pml risk high risk pml prior immunosuppression ii 18months continuous therapy iii positive hpyv2 jcv ab status 4 interferons interferonb1a im interferonb1a sc interferonb1b sc pegylated interferonb1a sc im 5 glatiramer acetate includes glatiramoids 6 decisions type therapy well therapy concept depend level disease activity severity thus first secondline therapies included hereavailable drugs listed alphabetically strength preferencescheme mstcg dgneurology kommentar 2021 https doiorg 101007 s42451021003533full size imageit generally agreed dmts better effect early course ms recent registry data indicate later initiation dmt leads extensive disability longer term 1 2 3 addition preventing acute episodes disease prophylactic therapy may reduce risk longterm neurologic deterioration secondary progression 4 longterm therapeutic benefits strongly depend early dmt starteddue great heterogeneity clinical ms course individual patients course extremely difficult predict although term benign ms abandoned eventually may courses lead significant disability 30years even without therapy overall analyses 1520 patients may accumulate measurable disability longer term reliable accepted predictors course without substantial disability hence dmt ms must started early possible diagnosis avoid future disability individual cases waitandsee approach regular neurological imaging checks may also considered patients low lesion burden complete remission mild clinical symptomsin context clinically isolated syndrome cis suggestive central nervous system demyelination defined monofocal multifocal clinical event eg optic neuritis spinal cord brain stem hemispheric syndrome mstcg takes proactive position management patients currently three licensed medical treatments available cis patients interferonb1a im interferonb1a sc interferonb1b sc interestingly usa siponimod recently approved additional option furthermore utmost importance early phase disease affected patients become aware compliant need monitor situation ensure best possible treatment management long term prevent disease activity neurodegeneration includes clinical mri followup patient education specific phase disease persons isolated optic neuritis without evidence cns pathology mri possibility progression ms hence disease monitoring without treatment can option consider discussion patient 5 patients evidence cns lesions oligoclonal bands fulfill mri criteria full ms diagnosis medical therapy needs clearly favored advised pure monitoring approach decisionmaking joint process requiring responsible choice affected patient case immediate medical treatment disease monitoring will continued uphold opportunity effective early therapeutic interventiongenerally exclusion differential diagnostic causes cis patients regardless whether criteria dit dis met must offered immunotherapy choice immunotherapy based predictive parameters primarily mri findings number localization lesions also ii extent relapse regression iii multifocal presentation iv csfspecific ocb chronic inflammatory csf changes cis patients high lesion burden infratentorial lesions diagnostic mri immunotherapy actively recommended given presumed unfavorable prognosis depending individual circumstances highefficacy therapy can considered already initial treatment importantly treatment cis unnecessarily delayed follow escalation approach individual highlyactive caselast least already cis can considered ms several colleagues opinions latest revision mcdonald criteria allows diagnosis ms many cases previously considered cis 6 7 question 2 diseasemodifying therapy selected less potent lowrisk therapy initially selected patients patients immediately receive highefficacy therapy higher risk profile requiring complex monitoring considered context escalation three stages versus individually adjusted escalationpresently two treatment approaches dominate selection optimal therapy highly active ms strategies based evaluating individual patients risk ms progression considering risk versus efficacy specific diseasemodifying therapies according escalation approach lowerefficacy therapies known relatively safe risk profile selected initial treatment despite sufficiently long regular treatment disease activity persists recurs treatment escalated potent therapy option alternative approach treatment initiated highefficacy diseasemodifying therapy already time diagnosis example alemtuzumab cladribine natalizumab ocrelizumab ofatumumab s1p receptor modulators fingolimod ozanimod ponesimod limiting current treatment recommendations escalation approach insufficient regarding current data situation diminishes possibilities start treatment higherefficacy medicationthe dgn guideline attempts grade diseasemodifying therapies according potency thus divides medications three groups view mstcg scientifically unsound minimal differences percentage relapse reduction formally compared drugs due different study collectives problematically scientifically wellfounded approach ultimately results threepart division therapy algorithm consisting first lowpotent mediumpotent finally highpotent therapy stepwise escalation described preferential approach correspond established consensus recommendations new study findings european international therapy concepts according time therapy earliest possible also potency therapy influences longterm outcome thus meanwhile proactive therapy concepts freedom therapy ultimately restricted threepart escalationchoosing first dmt ms patients challenging choice must occur individual patient level take account several factors clinical symptoms mri activity efficacy therapeutic agent side effects therapeutic agent handling route administration patients life circumstances family situation 8 9 general rule applies potent dmt higher potential risk severe side effects escalation regimen therapy always started less effective drug switched highefficacy dmt disease activity persists initially advocated dmts available availability multiple highefficacy dmts including depleting therapies hithardandearly concept postulated recommending use highefficacy dmt disease onset analogy example rheumatology controlled trials might demonstrate superiority one therapeutic approaches now initiated results will available several years retrospective registry studies already suggest patients disease activity early use highefficacy dmt compared lowerefficacy dmt may delay subsequent disability progression transition spms 2 4 underlying reason may concordance delaying therapy initiation early disease persistent clinical subclinical disease activity less effective therapy may cause irreversible neurological deficits allow activation signaling pathways associated progressive disease otherwise preventedhighefficacy therapies suitable every patient require individual riskbenefit assessment depleting immune reconstitution therapies irts including autologous hematopoietic stem cell transplantation special position regard cause profound changes immune system thus one hand show higher risk severe side effects notably increased risk infection first months therapy pulse hand proportion patients profit disease stabilization therapeutic effects persisting years beyond end therapy inducing longlasting therapyfree disease stability 10 11 12 substancespecific risk reduction strategies need applied comparison conventional immunotherapies require continuous therapy cumulative risks time counting towards individual riskbenefit balanceconsidering disease course long term advantage using highefficacy versus lowerefficacy dmts beginning treatment strategy supported registry data although prospective studies lacking due likely increased risk severe side effects consideration individual life circumstances use highefficacy dmts beginning disease decided individually following neurologists recommendations patients wishesdifferent therapy concepts exist within group highefficacy dmts sustained therapy efficacy relatively immediate application accompanied reversibility discontinuation natalizumab s1p receptor modulators well ocrelizumab ofatumumab limitation due mechanism action versus ii pulsed therapy efficacy due immune depletion repopulation significantly beyond halflife drug possibly also permanent therapyfree disease stability alemtuzumab cladribine possibly ocrelizumab severe limitation due mechanism action although dgn guideline mentions chronic continuous versus pulsed therapy approaches clearly prefers chronic therapy approach justified pointing towards lack longterm data pulsed therapies however correct ultimately education therapy concepts must provided especially since patient must informed possibility disease stabilization without continuous therapy 10 question 3 immunotherapy terminated therapy generally terminated 5 years longterm sometimes permanent therapy feasible considered context problem disease reactivation reboundthe scientific data clinically highly relevant question scarce available data result retrospective observational studies mostly older injectable ms therapeutics comprising relatively small cohorts prospective paper global ms database describes relapse rates remain stable discontinuation injectable ms therapies disease progression significantly accelerated 13 results consistent smaller retrospective observations treatment well tolerated safe patients motivated continuespecial consideration must given agents inhibiting leukocyte migration natalizumab s1p receptor modulators fingolimod ozanimod ponesimod siponimod discontinuation without concept followup treatment exception due possible recurrence even rebound disease activity challenging situations arise example context pregnancy lactation surgery irts alemtuzumab cladribine within limitation maybe also ocrelizumab special cases sense disease stability without followup treatment part therapeutic concept available data indicate 50 patients can stable many years alemtuzumab without need followup treatment including possibility treating recurrent disease activity cd52 depletion prospect achieving restabilization controlled studies currently exist discontinuation bcell depleting drugs however reversible mechanism action therefore ultimately return disease activity can expected due bcell dominance depletion principle established prognostic diagnostic markers dynamics depleting vs repopulating immune cell types indicate durable remission specified group exist ms hence also irts require established guidelines monitoring appropriate action plans recurring disease activitymore attention now paid disease activity relation age effects therapy relating age phenomena immune senescence versus immunocompetence old age roughly inflammatory activity effect immunotherapy especially influence progression decrease age weighing therapeutic goals benefitrisk profile considering disease activity becomes important especially higher age 50 generally recommend ms patients stable given dmt receive clinical radiological monitoring without safety tolerability issues continue therapy discontinuing pausing treatment associated risk recurrence disease activity progression depending mechanism action discontinuing pausing treatment patients explicit request without planned followup therapy may done adhering clear guidelines clinical imaging monitoringthe dgn guideline positions clearly towards discontinuation diseasemodifying therapy long term strongly recommends possibility 5years point view mstcg recommendation feasible considering available data can even create risks patients discontinuation pausing therapy explicit request patient without planned followup therapy can take place clear conditions clinical imaging monitoring means rule corresponding discontinuation studies just initiated internationally hand clear epidemiological data possible reactivation sense disease progression time well data reactivation rebound discontinuation immunomodulatory drugs addition increased disease activity rebound may occur discontinuation natalizumab s1p receptor modulators line critique point view mstcg dgn guideline balances medication safety patient higher modern options longterm disease stabilizationseveral studies reports describe development ms clinical paraclinical disease activity discontinuing dmt course discontinuation depends various factors disease severity individual patient disease duration comorbidities type dmt pulsed immunotherapies tend stabilize disease longer term maintenance therapies suggest rapid return disease activity cessation therapy sequence also essential 14 15 addition immunopathogenic factors genetics environment lifestyle another factor consider differences washout periods ie times discontinuation substance initiation followup treatment typically one six months special consideration context given drugs affect leukocyte migration 16 17 addition expected recurrence disease activity due discontinuation various reports describe rebound meaning return disease activity level exceeding start therapy although numerous studies describe effect fingolimod natalizumab rebound occur every individual discontinuing therapies however appropriate followup treatment always administered fingolimod natalizumab prevent potential recurrence disease activityhence discontinuation suspension medication therapy highly active ms either based suboptimal efficacy safety concerns must accompanied clear followup concept following factors considered selecting followup medication 1 disease activity clinical mri higher disease activity larger need immediate initiation new therapy 2 disease severity 3 halflife well biological activity previous medication differentiation socalled maintenance therapies natalizumab s1p receptor modulators partly ocrelizumab pulsed therapies alemtuzumab cladribine partly ocrelizumab 4 risk carryover pml reduced much possible clinical mri liquid diagnostic parameters detection hpyv2 jcv dna pcr used determine baseline preconversion status risk recurrence disease activity rebound especially leukocyte migration therapies natalizumab s1p receptor modulators considered can expected 26months discontinuation agentsfor spms uncertainties may arise line patients initially active disease treated longer relapses various experts including authors north american guideline recommend discontinuing therapy pure progression without relapse however unclear whether dmt suppresses relapse activity despite affecting progression meaning patients continue benefit relapse rate reduction provided dmt therapy discontinued spms patients close monitoring subsequential inflammatory activity essentialquestion 4 strongly aspects specified official therapy approval reflected treatment recommendation considered context equivalent recommendation rituximab offlabel use ocrelizumab approved bcelldepleting therapy onlabel appropriatedrugs approved regulatory agencies following detailed rather rigid process approvals therapies associated distinct labels regarding ms therapies labels usually related populations tested positive benefitrisk ratio can assumed formally means approved drugs can used prerequisites conditions provided within label medicolegal aspect must neglectedguidelines certainly asked put approval texts given context disease treatment concept however guidelines priori conflict liberty treatment choice create medicolegal conflict situations recommending offlabel therapies onlabel therapies availablewith regard dgn guideline relevant problems generated expressed preference escalation approach categorization drugs three classes efficacy stands conflict scientific basis effectiveness efficacy classes see question 2 approval textsin recent years anticd20 antibodies become established therapeutic option relapsing ms ocrelizumab approved since 2018 developed rituximab never formally approved ms treatment offlabel use ofatumumab administered subcutaneously received approval march 2021a critical problem generated potential offlabel use cd20 antibody rituximab based assumed similarity molecular target rituximab approved ms despite broad offlabel use various countries worldwide placed equal footing preparations bcell therapy ocrelizumab ofatumumab problematic since available class evidence study results formally allow statement rituximab hand ocrelizumab ofatumumab provided strong class evidence phase iii trials studying efficacy safety cd20 antibodies headtohead comparison opera oratorio asclepios trials ocrelizumab also first compound ever approved ppms relatively small wellstructured pivotal study significant delay disability progression since onset progressive ms particularly first year initiation therapy achieved patients 50years age active disease short disease duration resulted theoretical delay wheelchair use seven years 18 pivotal study indicates better efficacy younger patients shorter disease duration 19 ppms ocrelizumab thus currently approved treatment even effect ppms comparatively small measured edss least younger patients benefit therapy ocrelizumab especially since approved alternative data controlled trials older patients 55years longer disease course 15years higher degree disability edss score65 nevertheless according authors assessment therapeutic nihilism practiced particular patients risk losing physical independence therapeutic attempt justified patients quality life attempt can decisiveocrelizumab especially ofatumumab nextgeneration antibodies less murine compounds therefore reducing immunogenicity studies inform vaccination immune responses ms patients carried ocrelizumab 20 authors agree similar efficacy possible rituximab studied controlled conditions formally offlabel thus leads medicolegal problems context mstcg points importance providing treatment recommendations principle line approval texts offlabel therapy clearly possible case insufficient alternatives situations onlabel therapies sufficient control situationthe argumentation holds four available s1p receptor modulators one say active group ultimately distinct approvals partly due specific studies fingolimod rrms siponimod spms also due approval history first s1p receptor modulator fingolimod approved secondline therapy ensure safety best possible ultimately wrong initial decision however one say s1p receptor modulators must look specific approval situationsthe mstcg approached problem considering formal approval texts time dividing therapy scheme modern appropriate subdivisions relapsingremitting ms versus progressive ms fig 1 tactic guarantees maximum freedom therapy one hand hand also allows classification necessary therapy sequencea guideline recipe aspects complex individual level adaptive decision processavailability data materialsnot applicablereferences1chalmer t baggesen l m nrgaard m kochhenriksen n 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medical advisory boards national ms societies germany austria switzerland purpose developing evidencebased guidelines treatment msfundingnot applicableauthor informationaffiliationsklinik fr neurologie mit institut fr translationale neurologie westflische wilhelmsuniversitt mnster mnster germanyheinz wiendlneurologie st josefhospital ruhruniversity bochum bochum germanyralf goldklinik und poliklinik fr neurologie universittsmedizin der johannes gutenberguniversitt mainz mainz germanyfrauke zippconsortiafor multiple sclerosis therapy consensus groupthomas berger florian deisenhammer franziska di pauli christian enzinger elisabeth fertl michael guger fritz leutmezer orhan aktas karl baum martin berghoff stefan bittner achim gass klaus gehring norbert goebels ralf gold aiden haghikia hanspeter hartung fedor heidenreich olaf hoffmann boris kallmann christoph kleinschnitz luisa klotz verena leussink volker limmroth ralf linker jan d lnemann mathias murer sven g meuth uta meydinglamad michael platten peter rieckmann stephan schmidt martin stangel hayrettin tumani martin s weber frank weber heinz wiendl uwe zettl tjalf ziemssen frauke zipp andrew chan adam czaplinski tobias derfuss renaud du pasquier claudio gobbi andreas lutterotticontributionshw rg fz contributed writing answers 4 predefined questions mstcg authors read approved final manuscript,1.0
neuromyelitis optica concomitant pulmonary tuberculosis case report background concomitant diagnosis neuromyelitis optica spectrum disease pulmonary tuberculosis rarely reported case reportwe report case involving young tunisian male patient developed dry cough followed 2 months later weakness lower limbs findings central nervous system imaging antiaquaporin4 antibody positivity compatible diagnosis neuromyelitis optica spectrum disease constellation clinical typical radiological pulmonary findings patient coming endemic region allowed diagnosis pulmonary tuberculosis although sputum smear examination acidfast bacilli cultures negative patient received antituberculous polytherapy associated immunomodulation consisting methylprednisolone intravenous immunoglobulins pulmonary infection symptoms initially improved motor recovery patient suddenly died home 4 months onset first symptoms current data regarding clinical presentation underreported concomitant associated condition possible pathophysiological mechanisms therapeutic options reviewedconclusionsthis case underscores necessity understand exact mechanism coincident entities clarify best immunomodulatory choice since immunosuppression targeting neuromyelitis optica spectrum disease can lead dissemination pulmonary tuberculosis,0.0
pragmatic applications implementation science frameworks regulatory science assessment fda risk evaluation mitigation strategies rems 20142018 background risk evaluation mitigation strategy rems drug safety program certain medications serious safety concerns required us food drug administration fda manufacturers implement help ensure benefits medication outweigh risks fda encouraging research community develop novel methods assessing rems conveying unmet need standardized evaluation method regulatorymandated healthcare programs objective research evaluate fda rems assessment plans using established implementation science frameworks identify opportunities strengthening rems evaluationmethodsa content analysis conducted publicly available assessment plans rems programs n 23 approved 1 1 201412 31 2018 new drug applications ndas biologics license applications blas requiring fdamandated elements assure safe use etasu blinded reviewers critically appraised rems assessment measures n 674 using three established implementation science frameworks reaim reach effectiveness adoption implementation maintenance precedeproceed predisposing reinforcing enabling constructs educational environmental diagnosis evaluation policy regulatory organizational constructs educational environmental development cfir consolidated framework implementation research framework constructs mapped rems assessment categories defined fda guidance industry evaluate congruenceresultsrems assessment measures demonstrated strong congruence 90 mapping rate evaluative constructs reaim precedeproceed cfir application frameworks revealed rems assessment measures heavily emphasize implementation operations focus less health outcomes evaluate program context design assumptionsconclusionsimplementation science frameworks utility evaluating fdamandated drug safety programs including selection primary measures determine whether rems goals met secondary measures evaluate contextual factors affecting rems effectiveness varying organizational settings,0.0
survey diagnostic treatment practices multiple sclerosis russian federation comparison european data abstractintroductionthe data survey european eu neurologists methods diagnosis treatment multiple sclerosis europe compared data similar survey neurologists russian federation rf methodseventyfive neurologists specialized ms rf completed questionnaires radiologically isolated syndrome ris clinically isolated syndrome cis relapsingremitting rrms secondary progressive spms primary progressive ppms multiple sclerosisresultsin case ris 46 neurologists rf recommended csf analysis oligoclonal igg 543 performed magnetic resonance imaging mri spinal cord significantly lower eu 78 80 respectively case cis significantly neurologists russian federation tested antibodies disorders optical spectrum neuromyelitis 57 eu 94 rf case typical rrms neurologists rf preferred start second line diseasemodifying therapy dmt lower percentage choose dimethyl fumarate first line dmt 9 rf 25 eu case escalating therapy majority eu respondents 68 indicated one relapse sufficient 28 rf rf 58 indicated two relapses sufficient 22 eu fewer neurologists rf use fingolimod natalizumab mitoxantrone spms 91 neurologists rf like prescribe ocrelizumab ppmsconclusionms specialists rf less active monitoring ris ms specialists eu cis indication use dmt rf ms specialists rf conservative changing dmt escalation cases breakthrough rrms products without indication used spms rarely prescribed rf comparison eu cases ppms rf treated ocrelizumab,0.0
controversy treatment multiple sclerosis related disorders positional statement expert panel charge 2021 dgn guideline diagnosis treatment multiple sclerosis neuromyelitis optica spectrum diseases mogiggassociated disorders guidelines diagnosis treatment given disease intended ensure highquality medical care german neurological societys deutsche gesellschaft fr neurologie dgn guideline diagnosis treatment multiple sclerosis neuromyelitis optica spectrum diseases mogiggassociated disorders 1 recently revised published german consensusbased guideline s2k level according classification association scientific medical societies germany arbeitsgemeinschaft der wissenschaftlichen medizinischen fachgesellschaften ev awmf aims provide answers questions daily practice including areas evidence sparse without limiting physicians freedom decision clear focus set safeguarding patient autonomy end patient representatives involved throughout entire guideline development processkey question 1 patients receive diseasemodifying treatmentbefore onset disease progression even clinically isolated syndrome eg isolated optic neuritis selection timing diseasemodifying drugs dmds clinically isolated syndromes cis fulfilling 2017 diagnostic ms criteria multiple sclerosis ms one central issues addressed dgn guideline 1 ms prevention disability accrual central goal immunomodulatory treatments doubt start early according needin dgn guideline cis defined first manifestation relapse criterion dissemination space fulfilled dissemination time lack reliable predictive markers individual disease course response dmds makes treatment decisions challenging according dgn guideline purpose dmd treatment reduce relapse frequency slow progression disability decrease disease activity detected magnetic resonance imaging mri see appendix statement a14 patients experience first relapse without fulfilling criteria dissemination time space eg isolated optic neuritis myelitis therefore diagnosed ms cis basis 2017 criteria dmds used exceptionally see a20 since controlled studies dmds patient groupa central strong recommendation dgn guideline start dmds patients diagnosed cis relapsingremitting ms rrms see a16 based known positive effects early treatment longterm disease course 2 permanent disability can must avoided timely use dmdsthis recommendation line ectrims ean guidelines recommend dmds offered patients cis abnormal findings mri lesions suggestive fulfilling criteria ms propose early treatment dmds patients active rrms defined clinical relapses mri activity 3 additionally statement a24 strongly recommends dmds offered patients clinical mri activity within previous approximately 2yearsbeyond ectrims ean guidelines however dgn guideline aims provide specific guidance dmd selection particular situations eg offer treatmentnaive patients higherefficacy drugs start presence evidence probably highly active disease course outlined key question 2 notably observational studies 4 5 patients described mild ms longterm disease course despite absence reliably predictive markers individual prognosis disease onset taking account dgn guideline states one may consider weak recommendation refraining dmd initiation given benefits risks starting treatment thoroughly discussed patient provided patient monitored closely prerequisite consideration according guideline assumption mild disease course based patients characteristics time disease onset available subsequent disease course relevant characteristics include severity recovery first relapse relapse frequency mri lesion load activity cerebrospinal fluid parameters assessed see a16 notwithstanding panel feels several patient characteristics constitute unequivocal reasons initiation treatment first relapse young age polysymptomatic relapse incomplete recovery relapse high lesion load spinal infratentorial lesions mri intrathecal synthesis immunoglobulin g mgiven fact intrathecal immunoglobulin g m synthesis frequent ms 582 igg 217 igm recent study 6 cis ms based 2015 revised mcdonald criteria option initiate dmd clearly exception applicable small proportion patients number drops prognostic factors mentioned reviewed individual patientsoverall dgn guideline clearly recommends dmds treatment patients ms cis selected cases however clinical practice probably number option start dmd treatment first may considered provided individual patients characteristics indicative favourable disease course monitored closely option explicitly supported patient representatives involved panelkey question 2 patients receive diseasemodifying treatmentalways drugs limited efficacy established longterm safety first higherefficacy drugs fraction patients beginning individual choice rigid escalation treatmentwith dozen dmds now available categorisation drugs necessary facilitate treatment decisions panel felt dichotomisation baseline vs escalation dmds oversimplified particularly drugs latter category vary widely efficacy seeking suitable criterion panel decided use drugrelated reduction relapse rate available pivotal clinical trials although panel fully realises owing differences baseline characteristics study design measure compared across studies full scientific diligence represents absence headtohead clinical trials dmds acceptable approximation following concept panel agreed classify available dmds relapsing ms rms based relative reduction relapse rate mri activity relapserelated progression see a17 three categories efficacy see a18 efficacy category 1 betainterferons dimethyl fumarate glatirameroids teriflunomideefficacy category 2 cladribine fingolimod ozanimodefficacy category 3 alemtuzumab anticd20 antibodies ocrelizumab rituximab natalizumabthese categories intended provide orientation choosing appropriate drug given disease activity dictate therapeutic ladder instead immunotherapy rms selected individually based activity disease considering relapse frequency relapse severity response relapse therapy disease progression mri findings see a23 fig 1 fig 1figure1consensus reached category 1 drugs used firstline treatment dmdnaive patients unless disease course considered probably highly active see a25 efficacy category 2 3 dmds used category 1 drugs failed control disease however apart wellknown escalation approach category 2 3 agents also offered dmdnaive patients whose disease course considered probably highly active beginning see a29 choice category 1 3 thus follows stepin stepup approach olu offlabel use full size imagebut probably highly active unfortunately date unequivocal definition constitutes highly active disease least one derived controlled prospective clinical data striving fill gap panel members suggested criteria based findings 2018 ectrims focused workshop group aggressive ms 7 see a28 dmdnaive rms patients meeting one following clinical criteria considered suffering probably highly active msa relapse led clinical deficit affecting activities daily life despite relapse therapyrecovery insufficient following first two relapsesthe relapse rate high ie 3 approx first 2years or2 approx first year since disease onsetedss 3 approx first year since disease onsetpyramidal signs approx first year since disease onsetthe panel agreed mri criteria without clinical criterion insufficient assume probably highly active disease course dmdnaive patients presence criterion however mri findings high t2 lesion load one contrastenhancing lesion infratentorial spinal lesions considered high relevance selecting first dmd treatmentnaive patientsin addition mri criteria included working definition active disease despite dmd treatment patients rms dmd 6months disease defined active one following conditions fulfilled within preceding 2years see a32 confirmation relapse eg objective clinical findings relapse one new msspecific mri lesionat two time points one new msspecific mri lesionsthis definition linked strong recommendation see a33 patients active disease course treatment dmd efficacy category 1 switched dmd efficacy category 2 even 3 depending extent inflammatory activitythus dgn guideline advocates individual choice dmd treat patient needed may include timely dmd escalation dmd titration means mandatory treat hard early panel felt results ongoing prospective studies deliverms 8 treatms 9 expected 2023 awaited considering general recommendation unselected early aggressive treatmentinstead dgn guideline aims treat target approach requires definition dmd categories based efficacy definition probably highly active ms dmd naive patients definition inflammatory active ms patients dmd 6months based close monitoring throughout disease course guideline assists decisions growing number different dmds can offered individual patient including clear guidance use higherefficacy drugs outset dmd naive individuals considered suffer probably highly active mskey question 3 diseasemodifying treatment stoppedgenerally defined time eg 5years later sometimes reactivation rebound disease activationdiscontinuation dmd treatment important issue often addressed daily practice particular rms patients remained stable many years clinically radiologically exposed longterm immunotherapy whether possible safely stop treatment patients currently unresolved question patients inactive secondary progressive ms spms hopefully three ongoing prospective randomised trials two including patients rrms discoms 10 estimated completion date february 2022 dotms 11 estimated completion date january 2024 one including spms population older 50years stopisep 12 estimated completion date january 2026 will clarify impact treatment discontinuation focal disease activity disability progression foreseeable future date several observational studies concluded discontinuation mostly injectable dmd general impact freedom relapses may negative effects progression disability age gender disability baseline acquired within 3years withdrawal treatment mostly injectable drugs determine risk remaining stable long term 13 14 15 16 data accordance circumstantial evidence inflammatory component ms consequently efficacy dmd declines increasing age 17 18 taking account available evidence withdrawal treatment data observational studies implying mild longterm disease course 4 5 patients dgn guideline panel took opportunity draw recommendations treatment duration discontinuation see a60 highly selected patient groupsin rms patients anticipated mild disease course onset based clinical radiological features ie severity recovery first relapse relapse frequency mri lesion load activity csf parameters see a16 stable disease preceding 5years category 1 dmd treatment clinical radiological ms activity progression guideline gives weak recommendation pause category 1 dmd treatment b strongly emphasises patients informed advocated period 5years evidencebased data controlled trials assessing impact treatment discontinuation future relapses disability progression available c highlights decision whether pause pause dmd treatment taken strictly individual basis consideration individual patients wishes d demands regular clinical mri assessments monitor upcoming disease activity 6 12months subsequently every 12months following discontinuation treatment see a65 recommendation seemingly contradicts ectrims ean guidelines recommend consider continuing dmd patient stable clinically mri shows safety tolerability issues 3 rather ectrims ean guidelines pass question whether ever alternative permanent dmd treatment contrast dgn guideline cautiously broaches option dmd discontinuation distinct patient population fulfilling criteria described aboveinterestingly dgn guideline revives former suggestion 2006 recommendations escalating immunomodulatory therapy multiple sclerosis authored mstkg panel included similarly weak recommendation treatment discontinuation might considered least 3 years stable disease relapses disability progression stable mri taking consideration patients wish prerequisite patient education close monitoring 19 regarding category 2 3 dmds breakthrough rebound ms activity cessation natalizumab s1p modulators problably cd20 antibodies course issue thus dgn guideline states complete cessation drugs without substitution can means recommended even patients free disease activity 5years see a63 data needed fill knowledge gap proceed clinical situationkey question 4 strongly regulatory aspects reflected recommendationis appropriate equivalent recommendations rituximab offlabel ocrelizumab approved bcelldepleting therapies onlabel assessing efficacy safety tolerability therapeutic agents measures specific disease treatment situation medical guidelines primarily based available evidence totality evidence can come different sources addition pivotal phase ii iii studies may also include data retrospective case series registries cohort studies real world data respect virtually inevitable recommendations medical guidelines always congruent currently approved indications various drugs may even alternative recommending offlabel use olu approved drugs available certain medical need respect following constellations possible obvious offlabel uses can distinguished guidelinesin absence alternatives guideline recommends olu drug situations serious terms patients healththe guideline recommends specific active substance particular therapeutic situation manufacturers preparations explicitly approved indicationthe guideline discusses therapeutic procedures medications frequent use although scant evidence favour absence explicit advice practice guideline may interpreted sanctioning itthe guideline recommends specific therapeutic principle makes distinction regarding approval status substances show difference key aspects mechanism actionthe lawfulness feasibility olu differ substantially across eu german physicians allowed initiate olu medical practitioners socalled liberal profession right free choice therapy however strict rules apply olu respect liability issues patient education informed consent addition costs per se covered health insurance insurance funds means empowered grant reimbursement casetocase basis upon requestthe dgn guideline recommends olu several circumstancesfirst guideline recommends olu drugs labelled medications available often necessary treatment symptoms eg tremor ataxia nystagmus bladder dysfunction even standard comes firstline immunotherapy neuromyelitis optica spectrum diseases mogantibodyassociated diseasessecond guideline advocates use drugs form branded products different manufacturers may onlabel offlabel given indication eg gabapentin spasticity similarly guideline mentions drugs least partially proven efficacy german federal joint committee gba decided excluded reimbursement statutory health insurance funds eg phosphodiesterase5 inhibitors erectile dysfunction third guideline panel decided group anticd20 antibodies ocrelizumab rituximab substance class even though rituximab approved treatment ms main reason decision development clinical evaluation ocrelizumab clearly based early findings phase ii studies rituximab two therapeutic antibodies also nearly identical terms key pharmacological properties large cohort studies demonstrated longterm efficacy rituximab ms treatment 20 21 22 moreover ocrelizumab approved launched specialised centres common practice treat ms patients rituximab guideline group deemed essential ensure treatment patients long stable remains line prevailing guidelines change treatment might expose patient unjustified risk course using rituximab offlabel liability issues special reimbursement conditions typical olu must considered however initiation continuation treatment rituximab medical malpractice 23 constitutes option ms,0.0
chest pain midaged woman simply myopericarditis case report antiku positive polymyositis background antiku rare antibody can positive rheumatic diseases might related cardiac involvement polymyositis inflammatory myopathy cardiac involvement seldom presents myopericarditis antiku positivecase presentationin case report midaged woman chest pain upper limbs weakness fever unrelated infection diagnosis case unquestionably myopericarditis supported ecg cardiac mri negative findings coronary arteries diagnosis polymyositis clarified evidence persistently increased ck degeneration proximal muscle mri muscular dystrophy lymphocytes infiltration muscle biopsy analysis autoantibodies surprisingly discovered positive antiku glucocorticoid mycophenolate mofetil prescribed polymyositis patient followup indicated remission myopericarditis polymyositis finally clarified rare case positive antiku polymyositis myopericarditis cardiac involvementconclusionthis report presents rare case antiku positive polymyositis cardiac involvement polymyositis manifested myopericarditis therefore positive antiku might explain myopericarditis cardiac involvement polymyositis cases longer duration followup required comprehensive understanding disease,0.0
understanding impacts covid19 pandemic people multiple sclerosis treated ocrelizumab abstractthe coronavirus disease 2019 covid19 pandemic caused severe acute respiratory syndrome coronavirus 2 sarscov2 led major challenges therapeutic management patients living multiple sclerosis plwms particularly regarding use diseasemodifying therapies despite extraordinary scientific effort study sarscov2 plwms heterogeneity covid19 manifestations immunological mechanisms induced natural infection vaccines extent protection vaccines major knowledge gaps remain describe scientific evidence generation plan developed roche genentech better understand impact covid19 pandemic plwms treated bcell depleting monoclonal antibody ocrelizumab,0.0
antibody development covid19 vaccination patients autoimmune diseases netherlands substudy data two prospective cohort studies summarybackgrounddata scarce immunogenicity covid19 vaccines patients autoimmune diseases often treated immunosuppressive drugs aimed investigate effect different immunosuppressive drugs antibody development covid19 vaccination patients autoimmune diseasesmethodsin study used serum samples collected patients autoimmune diseases healthy controls included two ongoing prospective cohort studies netherlands participants eligible inclusion substudy vaccinated covid19 vaccine via dutch national vaccine programme time prioritising vaccination older individuals samples collected first second covid19 vaccination serial samples collected seroconversion rates igg antibody titres receptorbinding domain sarscov2 spike protein measured logistic linear regression analyses used investigate association medication use time vaccination least sampling seroconversion rates igg antibody titres studies data collected registered netherlands trial register trial id nl8513 clinicaltrialsorg nct04498286findingsbetween april 26 2020 march 1 2021 3682 patients rheumatic diseases 546 patients multiple sclerosis 1147 healthy controls recruited participate two prospective cohort studies samples collected patients autoimmune diseases n632 healthy controls n289 first 507 patients 239 controls second 125 patients 50 controls covid19 vaccination mean age patients controls 63 years sd 11 423 67 632 patients autoimmune diseases 195 67 289 controls female among participants without previous sarscov2 infection seroconversion first vaccination significantly lower patients controls 210 49 432 patients vs 154 73 210 controls adjusted odds ratio 033 95 ci 023048 p00001 mainly due lower seroconversion patients treated methotrexate anticd20 therapies second vaccination seroconversion exceeded 80 patient treatment subgroups except among treated anticd20 therapies three 43 seven patients observed difference seroconversion igg antibody titres patients previous sarscov2 infection received single vaccine dose 72 96 75 patients median igg titre 127 au ml iqr 27300 patients without previous sarscov2 infection received two vaccine doses 97 92 106 patients median igg titre 49 au ml 17134 interpretationour data suggest seroconversion first covid19 vaccination delayed older patients specific immunosuppressive drugs second repeated exposure sarscov2 either via infection vaccination improves humoral immunity patients treated immunosuppressive drugs therefore delayed second dosing covid19 vaccines avoided patients receiving immunosuppressive drugs future studies include younger patients need done confirm generalisability resultsfundingzonmw reade foundation ms center amsterdam,0.0
risk factors associated multiple sclerosis casecontrol study damascus syria letter editor interestingly read study done maher taan et al taan et al 2021 entitled risk factors associated multiple sclerosis casecontrol study damascus syri despite interesting subject current study lacks important elements matched casecontrol study may lead distorting results mentioned,0.0
trabecular bone texture analysis conventional radiographs assessment knee osteoarthritis review viewpoint background trabecular bone texture analysis tbta identified imaging biomarker provides information trabecular bone changes due knee osteoarthritis koa consequently important conduct comprehensive review permit better understanding unfamiliar image analysis technique area koa researchwe examined tbta conducted knee radiographs associated koa incidence progression ii total knee arthroplasty iii koa treatment responses primary aims study twofold provide narrative review studies conducted radiographic koa using tbta ii viewpoint future research prioritiesmethodliterature searches performed pubmed electronic database studies published june 1991 march 2020 related traditional fractal image analysis trabecular bone texture tbt knee radiographs identifiedresultsthe search resulted 219 papers title abstract scanning 39 studies found eligible classified accordance six criteria crosssectional evaluation osteoarthritis nonosteoarthritis knees understanding bone microarchitecture prediction koa progression koa incidence total knee arthroplasty association treatment response numerous studies reported relevance tbta potential bioimaging marker prediction koa incidence progression however studies focused association tbta oa treatment responses prediction knee joint replacementconclusionclear evidence biological plausibility tbta koa already established review confirms consistent association tbt important koa endpoints koa radiographic incidence progression tbta provide markers enrichment clinical trials enhancing screening koa progressors major advances made towards fully automated assessment koa,0.0
tamoxifen application associated transiently increased loss hippocampal neurons following virus infection int j mol sci 2021 aug 6 22 16 8486 doi 103390 ijms22168486abstracttamoxifen frequently used murine knockout systems creer loxp besides possible neuroprotective effects tamoxifen described negative impact adult neurogenesis present study investigated effect highdose tamoxifen application theilers murine encephalomyelitis virus tmev induced hippocampal damage two weeks tmev infection 42 untreated tmevinfected mice affected marked inflammation neuronal loss whereas 58 exhibited minor inflammation without neuronal loss irrespective presence neuronal loss untreated mice lacked tmev antigen expression within hippocampus 14 days postinfection dpi interestingly tamoxifen application 0 2 4 5 7 9 dpi decelerated virus elimination markedly increased neuronal loss 94 associated increased reactive astrogliosis 14 dpi t cell infiltration microgliosis expression water channels similar within inflammatory lesions regardless tamoxifen application applied 0 2 4 dpi tamoxifen negative impact number doublecortin dcx positive cells within dentate gyrus dg 14 dpi without longlasting effect neuronal loss 147 dpi thus tamoxifen application tmev infection associated transiently increased neuronal loss hippocampus increased reactive astrogliosis decreased neurogenesis dgpmid34445189 doi103390 ijms22168486,1.0
health care transition patients vascular malformations french multicenter crosssectional study background health care transition ie transition pediatric adult care challenging chronic conditions poorly studied rare chronic skin diseases investigated proportion lost followup among patients superficial vascular malformations health care transition also collected patients opinions prospective multicenter crosssectional study performed 7 french hospitals included patients aged 1925 years followed superficial vascular malformation age 16 completed transition period 2020 data collected medical records questionnaire sent included patients asking health care transitionresultsamong 90 patients included 41 46 lost followup health care transition period age diagnosis significantly higher lost followup non lost followup patients lost followup proportion similar patients changed change hospitals transition responses questionnaire obtained 47 90 patients 522 response rate satisfied care n 31 36 861 however lack psychological support reportedconclusionshealth care transition associated high rate lost followup early management seems associated less lost followup studies needed better understand risk factors failed health care transition consequences,0.0
human sensorimotor organoids derived healthy amyotrophic lateral sclerosis stem cells form neuromuscular junctions nat commun 2021 aug 6 12 1 4744 doi 101038 s41467021247764abstracthuman induced pluripotent stem cells ipsc hold promise modeling diseases individual human genetic backgrounds thus developing precision medicine generate sensorimotor organoids containing physiologically functional neuromuscular junctions nmjs apply model different subgroups amyotrophic lateral sclerosis als using range molecular genomic physiological techniques identify characterize motor neurons skeletal muscle along sensory neurons astrocytes microglia vasculature organoid cultures derived multiple human ipsc lines generated individuals als isogenic lines edited harbor familial als mutations show impairment level nmj detected contraction immunocytochemical measurements physiological resolution human nmj synapse combined generation major cellular cohorts exerting autonomous noncell autonomous effects motor sensory diseases may prove valuable understand pathophysiological mechanisms alspmid34362895 doi101038 s41467021247764,0.0
infantile hemiconvulsionhemiplegia epilepsy ihhe boy tuberous sclerosis complex epilepsy behav rep 2021 aug 6 16100473 doi 101016 jebr2021100473 ecollection 2021abstracttuberous sclerosis complex tsc rare autosomal dominant disease due pathogenic variants tsc1 tsc2 genes brain tsc associated multiple cortical subcortical malformations including tubers abnormalities radial neuronal migration approximately 80 patients develop epilepsy first two years life often focal seizures infantile spasms seizure disorders systemic illness fever can trigger seizure result status epilepticus even refractory status epilepticus infantile hemiconvulsionhemiplegia epilepsy ihhe considered subcategory newonset refractory status epilepticus norse presents hemiclonic seizures setting fever unihemispheric brain imaging abnormality hemiparesis present 18monthold boy tsc developed ihhe extensive brain malformations neuronal hyperexcitability perituberal tissue predisposed ihhe addition factors postulate another prerequisite ihhe likely genetic predisposition excessive inflammatory response yet elucidatedpmid34466799 pmcpmc8383053 doi101016 jebr2021100473,0.0
incremental burden comorbid major depressive disorder patients type 2 diabetes cardiovascular disease retrospective claims analysis background estimated prevalence comorbid major depressive disorder mdd 11 patients type 2 diabetes t2d 1520 cardiovascular disease cvd comorbid mdd continues significant source economic burden healthcare systemmethodswe assessed incremental healthcare burden comorbid mdd patients t2d cvd realworld retrospective administrative claims study analyzed commercially insured adults t2d cvd diagnosed least 2 separate claims within 12 months january 1 2011 september 30 2018 cvd included congestive heart failure peripheral vascular disease coronary heart disease cerebrovascular disease study compared patients without mdd either t2d cvd study assessments included allcause healthcare resource utilization proportion patients hospitalization emergency department ed visits outpatient visits costresultspatients matched propensity score demographics baseline characteristics resulting similar baseline characteristics respective subcohorts matching 22 892 patients t2d 11 446 without mdd 28 298 patients cvd 14 149 without mdd includedat followup patients t2d mdd significantly higher rates hospitalization 261 vs 174 p 00001 ed visits 553 vs 430 p 00001 observed patients without mdd total cost patients t2d mdd followup significantly higher without mdd 16 511 vs 11 550 p 00001 similarly followup patients cvd mdd significantly higher rates hospitalization 454 vs 341 p 00001 ed visits 665 vs 554 p 00001 observed patients without mdd total cost followup patients cvd mdd significantly higher without mdd 25 546 vs 18 041 p 00001 conclusionspatients either t2d cvd comorbid mdd higher total allcause healthcare utilization cost similar patients without mdd study findings reinforce need appropriate management mdd patients comorbid diseases turn may result cost reductions payerstrial registrationnot applicable,0.0
consensus consensus ms chronic heterogeneous disease pathogenesis derives complexities immune central nervous system lends self evidence based treatment guidelines consensus statements guide therapeutic decisions even case view rapidly increasing number available compounds therapeutic strategies now available different stages diseaseguidelines consensus statements aim provide orientation less specialized health care professional inform patients help defining common standards care harmonizing treatment policies often implications reimbursement wide range implications including important financial interests value acceptance guidelines depends transparency development process scientific professional authority recognition involved particularly comes softer recommendations derived unequivocal evidencegerman neurologists participation authors austria switzerland tradition valuable contributions since earlier recommendations ms therapy consensus group mstkg 1 2 recently competence network multiple sclerosis https wwwkompetenznetzmultiplesklerosede wpcontent uploads 2018 11 kknms_qualitc3a4tshandbuchmsnmosd_2018_webfreipdf authors refrained providing consensus recommendations clinically important topics evidence still scarce 2021 guideline 3 german neurological society presented comprehensive thoroughly revised document although derived adherence procedures defined association scientific medical societies germany s2k level consensusbased guidelines https wwwawmforg leitlinien awmfregelwerk llentwicklung awmfregelwerk01planungundorganisation postufenklassifikation klassifikations2kunds2ehtml statements criticized leading ms experts involved gns guideline committee 4 debate key timely issues high interest ms deserve attention broader clinical scientific audience editor neurological research practice asked protagonists debate answer four questions address central topics controversy 5 6 authors two statements can commended well thought contributions explain respective rationales eg interpretations current evidence clinical trials real life studies underlying concepts disease pathogenesis mode action dmts allow readers draw conclusionsmy overall impression disagreement may less initially assumedquestion 1 early initiation treatment agree prevention disease activity depicted mri lesions relapses worsening depicted thorough comprehensive assessment cns function reaction already established damage preferred strategy also agreement early treatment effective strategy reach goals differences exist regarding early early rigor recommending treatment bayas colleagues 5 suggest expectative attitude cis patients fulfill formal criteria dissemination space also seem inclined accept exceptions therapeutic imperative established ms individual patient characteristics indicative favorable disease course also declare option initiate dmt clearly exception applicable small proportion patients wiendl et al 6 take stand patients established ms diagnosis also cis patients need offered immunotherapy regardless whether criteria dissemination time space met long plausible differential diagnosistaking account definition benign disease course possible predictors remains elusive 7 controlled studies shown positive benefit risk balance initiating treatment early cis participation restricted fulfillment current criteria dis inclined follow approach proposed wiendl et al daily practicequestion 2 selection dmt treatment strategy agree individual assessment disease characteristics potential risks guide choice treatment full spectrum available options needs considered even early stages ms treatment nave patients comes defining candidates higher efficacy treatments bayas et al 5 restrict option treatment failures category 1 compounds treatment nave patients probably highly active disease define following recommendations recent workshop aggressive ms 8 wiendl et al 6 suggest open approach early high efficacy treatment encouraged accumulating evidence several registry based observational studies supporting benefits early high efficacy treatments 9 10 author groups acknowledge results controlled prospective studies comparing benefitrisk balance early high efficacy treatment approach hit hard early versus escalation approach still pending bayas et al categorize available dmds three groups mainly according effects relapse rates different studies propose escalating approach majority patients wiendl et al underscore available treatments deserves thorough appraisal individual ms still mention number dmds classify preferentially indicated mild moderate ms optimal control disease activity progression goal concerns risk tolerability can prevent using effective treatment options manageable risk convenience profile emerging long term extensions large controlled studies 11 12 13 systematic follow real world settings 9 10 high efficacy treatments namely s1p modulators anticd20 monoclonal antibodies natalizumab jc virus negative patients probably even extended interval dosing 14 alleviate concerns morequestion 3 refers long term continuation dmts know ms still disease without cure exception intensive cell depleting therapies given intermittently may long term effects thereafter even leading immune reconstitution permanent recovery proportion patients treatments need given continuously achieve effects nevertheless substantial proportion pwms 6070 different surveys take part prescribed medication discontinue treatment within first 15years initiation 15 16 neurologists sanction practice stable patients bayas et al 5 although stating conclusive evidence exists safety stopping dmt several years stability observational studies indicated negative effects discontinuation disability progression suggest consider discontinuing treatment close clinical mri monitoring 5years stability wiendl et al 6 strongly recommend patients stable given treatment continue therapy long safety tolerability issues pending results ongoing controlled studies assessing riskbenefit profile treatment discontinuation 17 18 endorse reasoning daily practicequestion 4 refers interdependence scientific evidence framework provided official labels defined regulators respective health care system bayas et al argue mode action available evidence phase ii observational studies document high grade similarity chimeric anticd20 antibody rituximab humanized anticd20 antibody ocrelizumab therefore allow including rituximab although approved ms equivalent option recommendations wiendl et al propose adhere official labels restrict label use situations approved equally effective tolerable compounds available concur regulators legally defined role balancing riskbenefit therapeutics interest society including financial considerations treating physicians clinical scientists respect role long doesnt compromise best interest patientsin conclusion doubt treatment multiple sclerosis radically improved lifes mid long term expectation people diagnosed ms able conduct normal life still enough improve especially regarding better control even prevention disease progression great part current controversy due differing views affordable risk relation achievable benefits treatment available dmts systematic comparative studies controlled observational together comprehensive evaluation pwms phases disease will hopefully produce kind evidence needed better inform debate personalized treatment decisions,0.0
concentration levels serum 25hydroxyvitamind vitamin d deficiency among children adolescents india descriptive crosssectional study background vitamin d essential micronutrient overall health wellbeing individuals strong musculoskeletal neurological development human body vitamin d levels childhood adolescence key importance first nationallevel study analyzes deficiency concentration serum 25hydroxyvitamin d 25 oh d among indian children adolescents respect various demographic socioeconomic characteristicsmethodsdata comprehensive national nutrition survey cnns 201618 utilized present study vitamin d levels assessed based serum 25hydroxyvitamin d concentration prevalence vitamin d deficiency shown three age groups 04 years n 12 764 59 years n 13 482 1019 years n 13 065 vitamin d deficiency defined serum 25 oh d 12 ng ml insufficiency 12 ng ml 25 oh 20 ng ml 25 oh d level higher 20 ng ml accepted adequate random slope multilevel logistic regression models employed assess demographic socioeconomic correlates vitamin d deficiencyresultsmean serum 25 oh d concentration level found 1951 876 1773 791 1707 816 ng ml age group 04 years 59 years 1019 years respectively 4912 children aged 04 years insufficient level vitamin d prevalence vitamin d deficiency comparatively higher among female adolescents 7616 adolescents living rural region 6748 sikh individuals 04 years 7628 59 years 9026 1019 years 8956 adolescents coming rich households northindian individuals substantially higher odds vitamin d deficiency three age groupsconclusionthe present study demonstrated prevalence vitamin d deficiency considerably high among children adolescents india study highlights highrisk group require prompt policy interventions,0.0
progressive brain microstructural damage patients multiple sclerosis patients neuromyelitis optica spectrum disorder crosssectional follow tractbased spatial statistics study abstractbackgroundneuromyelitis optica spectrum disorder nmosd may sometimes misdiagnosed multiple sclerosis ms disorders similar clinical presentations commonly show white matter damage brain diffusion tensor imaging dti advanced mri technique assess microstructural organization white matter provides greater pathological specificity conventional mri present combined crosssectional longitudinal study novel dti technique trackbased spatial statistics tbss used investigate difference dti parameter abnormalities nmosd msmethodsa total 42 patients nmosd 51 patients ms 56 health controls hc recruited 14 patients nmosd 13 patients ms also studied followup average interval approximately one year measurements fractional anisotropy fa mean diffusion md axial diffusivity ad radial diffusivity rd compared baseline followup patients nmosd msresultssignificant reduction fa increase md ad rd observed patients ms p 005 reduced fa shown nmosd p 005 compared hc effects together lesion load t1wi t2wi greater patients ms patients nmosd p 005 significant difference time interval followup patients ms 137 years nmosd 125 years p 005 significant changes edss score baseline followup nmosd ms patients p 005 significantly reduced fa increased md rd patients ms p 005 significant changes patients nmosd p 005 conclusionsboth ms nmosd microstructure damage white matter progressive change brain microstructural properties observed patients ms may patients nmosd shortterm followup,0.0
osteomyelitis variolosa issue inherited past case report systematic review background osteomyelitis variolosa selflimiting disease triggered variola virus prevented repaired smallpox eradicated 40 years complications remain smallpox cured become remarkable diagnostic challenge contemporary physicians systematic review searched pubmed medline web science google scholar cases complications diagnosis treatment osteomyelitis variolosa january 1980 february 2021resultsten papers eleven finished cases patients india included comparison present case total 100 patients presented bilateral elbow deformities ankle second common site lesion 50 knee lesions accounted 25 study flexion contracture joint instability secondary arthritis fracture common complications osteomyelitis variolosa patients receive conservative treatment internal fixation good results combined fracturesconclusionsalthough osteomyelitis variolosa direct threat safety patients severe skeletal deformities can significant impact quality life advances surgical techniques clinicians offering increasing number treatment options patients osteomyelitis variolosa however importantly smallpox basically removed historical arena areas smallpox endemic physicians need deepen understanding disease,0.0
clinical imaging outcomes intrathecal injection umbilical cord tissue mesenchymal stem cells cerebral palsy randomized doubleblind shamcontrolled clinical trial background study assessed safety efficacy intrathecal injection umbilical cord tissue mesenchymal stem cells uctmsc individuals cerebral palsy cp diffusion tensor imaging dti performed evaluate alterations whitematter integritymethodsparticipants 414 years old spastic cp assigned 11 ratio receive either uctmsc sham procedure singledose 2 107 cells administered experimental group small needle pricks lower back performed shamcontrol arm individuals sedated prevent awareness primary endpoints mean changes gross motor function measure gmfm 66 baseline 12 months procedures mean changes modified ashworth scale mas pediatric evaluation disability inventory pedi cp quality life cpqol also assessed secondary endpoints mean changes fractional anisotropy fa mean diffusivity md corticospinal tract cst posterior thalamic radiation ptr resultsthere 36 participants group mean gmfm66 scores 12 months intervention significantly higher uctmsc group compared baseline 1065 95ci 539 1591 control 807 95ci 162 1452 cohens d 092 increase also seen total pedi scores vs baseline 853 95ci 498 1208 vs control 687 95ci 152 1221 cohens d 070 mean change mas scores 12 months cell injection reduced compared baseline 10 95ci 131 069 control 072 95ci 118 026 cohens d 076 regarding cpqol mean changes domains including friends family participation activities communication higher control group large effect size dti analysis experimental group showed mean fa increased cst 0032 95ci 002 003 ptr 0024 95ci 0020 0028 md decreased cst 0035 103 95ci 004 103 002 103 ptr 0045 103 95ci 005 103 003 103 compared baseline mean changes significantly higher control groupconclusionsthe uctmsc transplantation safe may improve clinical imaging outcomestrial registrationthe study registered clinicaltrialsgov nct03795974,0.0
severely disabled multiple sclerosis patients can achieve performance healthy subjects expiratory muscle strength training abstractbackgroundthe efficacy expiratory muscle strength training emst patients multiple sclerosis ms controversial current studynulls primary objective test effects progressive intensive 12 week home based emst program expiratory muscle strength voluntary cough strength secondary objective determine retention emst benefitsmethodsthirtyfive severely disabled ms patients relapsingremitting ms n15 primary progressive ms n5 secondary progressive ms n15 expanded disability status scale edss 50 70 included study within 36 weeks patients completed 12 weeks nontraining period 12 weeks emst 12 weeks detraining period maximal expiratory pressure pemax voluntary peak cough flow vpcf assessed 4 times week 0 baseline week 12 pretraining week 24 posttraining week 36 postdetraining ms patients included study compared age sexmatched healthy subjects healthy controls pemax vpcf assessed obtain normative dataresultstwentysix patients completed training period mean age 527 102 edss 59 06 compared 26 sex agematched healthy subjects mean age 535 58 patients ms lower pemax p 0002 vpcf p 0022 baseline healthy control group training period pemax vpcf increased p 00000 effect size d094 p00036 d057 respectively comparison nontraining period p 00692 d036 p05810 d011 respectively following 12 weeks detraining period pemax vpcf declined remained 167 55 respectively pretraining values differences observed pemax vpcf ms group posttraining postdetraining timepoint healthy control group normative valuesconclusionsemst improves expiratory muscle strength voluntary cough strength severely disabled ms patients,0.0
monash autismadhd genetics neurodevelopment magnet project design methodologies dimensional approach understanding neurobiological genetic aetiology background asd adhd prevalent neurodevelopmental disorders frequently cooccur strong evidence degree shared genetic aetiology behavioural neurocognitive heterogeneity asd adhd hampered attempts map underlying genetics neurobiology predict intervention response improve diagnostic accuracy moving away categorical conceptualisations psychopathology dimensional approach anticipated facilitate discovery datadriven clusters enhance understanding neurobiological genetic aetiology conditions monash autismadhd genetics neurodevelopment magnet project one first largescale familybased studies take truly transdiagnostic approach asd adhd using comprehensive phenotyping protocol capturing dimensional traits central asd adhd magnet project aims identify datadriven clusters across adhdasd spectra using deep phenotyping symptoms behaviours investigate degree familiality different dimensional asdadhd phenotypes clusters map neurocognitive brain imaging genetic correlates datadriven symptombased clustersmethodsthe magnet project will recruit 1 200 families children either typically developing display elevated asd adhd asdadhd traits addition affected unaffected biological siblings probands parents children will comprehensively phenotyped behavioural symptoms comorbidities neurocognitive neuroimaging traits geneticsconclusionthe magnet project will first largescale family study take transdiagnostic approach asdadhd utilising deep phenotyping across behavioural neurocognitive brain imaging genetic measures,0.0
spopmediated ubiquitination degradation pdk1 suppresses akt kinase activity oncogenic functions background 3phosphoinositidedependent protein kinase1 pdk1 acts master kinase protein kinase g c family agc kinase predominantly govern cell survival proliferation metabolic homeostasis although regulations pdk1 downstream substrates protein kinase b akt ribosomal protein s6 kinase beta s6k well established upstream regulators pdk1 especially degrader defined yetmethoda clustered regularly interspaced short palindromic repeats crispr based e3 ligase screening approach employed identify e3 ubiquitin ligase degrading pdk1 western blotting immunoprecipitation assays immunofluorescence staining performed detect interaction location pdk1 speckletype poz protein spop immunohistochemistry ihc staining used study expression pdk1 spop prostate cancer tissues vivo vitro ubiquitination assays performed measure ubiquitination conjugation pdk1 spop vitro kinase assays mass spectrometry approach carried identify casein kinase 1 ck1 glycogen synthase kinase 3 gsk3 mediated pdk1 phosphorylation biological effects pdk1 mutations correlation spop mutations performed colony formation soft agar assays vivo xenograft mouse modelsresultswe identified pdk1 underwent spopmediated ubiquitination subsequent proteasomedependent degradation specifically spop directly bound pdk1 consensus degron ck1 gsk3mediated phosphorylation dependent manner pathologically prostate cancer patients associated mutations spop impaired pdk1 degradation thus activated akt kinase resulting tumor malignancies meanwhile mutations occurred around within pdk1 degron either blocking spop bind degron inhibiting ck1 gsk3mediated pdk1 phosphorylation markedly evade spopmediated pdk1 degradation played potently oncogenic roles via activating akt kinaseconclusionsour results reveal physiological regulation pdk1 e3 ligase spop also highlight oncogenic roles lossoffunction mutations spop gainoffunction mutations pdk1 tumorigenesis activating akt kinase,0.0
exploratory radiomic analysis conventional vs quantitative brain mri toward automatic diagnosis early multiple sclerosis front neurosci 2021 aug 5 15679941 doi 103389 fnins2021679941 ecollection 2021abstractconventional magnetic resonance imaging cmri poorly sensitive pathological changes related multiple sclerosis ms normalappearing white matter nawm gray matter gm added difficulty reproducible quantitative mri qmri hand attempts represent physical properties tissues making ideal candidate quantitative medical image analysis radiomics therefore hypothesized qmribased radiomic features added diagnostic value ms compared cmri study investigated ability cmri t1w qmri features extracted white matter wm nawm gm distinguish ms patients msp healthy control subjects hcs developed exploratory radiomic classification models dataset comprising 36 msp 36 hcs recruited chu liege belgium acquired cmri qmri image type region interest qmri radiomic models ms diagnosis developed training subset validated testing subset radiomic models based cmri developed entire training dataset externally validated opensource datasets 167 hcs 10 msp ranked region interest best diagnostic performance achieved whole wm model based magnetization transfer imaging type qmri features yielded median area receiver operating characteristic curve auc 100 testing subcohort ranked image type best performance achieved magnetization transfer models median aucs 079 069090 90 ci nawm 081 071090 gm external validation t1w models yielded auc 078 047100 whole wm demonstrating large 95 ci low sensitivity 030 010070 exploratory study indicates qmri radiomics provide efficient diagnostic information using nawm gm analysis msp t1w radiomics useful fast automated check conventional mri wm abnormalities acquisition reconstruction heterogeneities overcome prospective validation needed involving data better interpretation generalization resultspmid34421515 pmcpmc8374240 doi103389 fnins2021679941,0.0
effect comorbid mood anxiety disorders breast cervical cancer screening immunemediated inflammatory disease plos one 2021 aug 5 16 8 e0249809 doi 101371 journalpone0249809 ecollection 2021abstractwe aimed examine rates breast cervical cancer screening women immunemediated inflammatory diseases imid including inflammatory bowel disease ibd multiple sclerosis ms rheumatoid arthritis ra versus matched cohort imid examine association psychiatric comorbidity screening populations conducted retrospective cohort study manitoba canada using administrative data identified women ibd ms ra controls without imid matched age region annually identified individuals active mood anxiety disorder using physician claims determined proportion cohort cervical cancer screening within threeyear intervals mammography screening within twoyear intervals modeled difference proportion imid matched cohorts underwent mammography pap tests using logbinomial regression generalized estimating equations adjusting sociodemographics comorbidity immune therapy use tested additive interactions cohort mood anxiety disorder status 20062016 identified 17 230 women imid 4 623 ibd 3 399 ms 9 458 ra 85 349 matched controls imid associated lower 1 use mammography however reflected mixture mammography ibd cohort +29 less mammography ms 48 52 ra 15 cohorts within ibd ms ra cohorts active mood anxiety disorder associated mammography use inactive mood anxiety disorder ms ra cohorts less likely undergo pap testing matched cohorts absence active mood anxiety disorder ibd cohort likely undergo pap testing matched cohort opposite true active mood anxiety disorder present among women imid mood anxiety disorder influence participation cancer screeningpmid34351924 doi101371 journalpone0249809,0.0
memorable food fighting agerelated neurodegeneration precision nutrition front nutr 2021 aug 5 8688086 doi 103389 fnut2021688086 ecollection 2021abstracthealthcare systems worldwide seriously challenged rising prevalence neurodegenerative diseases ndds mostly exclusively affect evergrowing population elderly known neurodegenerative diseases alzheimers ad parkinsons disease multiple sclerosis amyotrophic lateral sclerosis viral infections brain traumatic brain injury may also cause ndd typical ndd malfunctioning neurons irreversible loss often progress irreversibly dementia ultimately death numerous factors involved pathogenesis ndd genetic variability epigenetic changes extent oxidative nitrosative stress mitochondrial dysfunction dna damage complex interplay abovementioned factors may fingerprint neurodegeneration different diseases affected different extents particular factors voluminous body evidence showing benefits regular exercise brain health cognitive functions moreover importance healthy diet balanced macro micronutrients preventing neurodegeneration slowing progression fullblown disease evident individuals affected ndd almost inevitably lowgrade inflammation anomalies lipid metabolism metabolic lipid profiles ndd can improved mediterranean diet many studies associated mediterranean diet decreased risk dementia ad causeandeffect relationship deduced studies caloric restriction showed neuroprotective effects animal models results humans inconsistent pathologies ndd complex great interindividual epi genetic variance within population furthermore gut microbiome deeply involved nutrient uptake lipid metabolism also represents pillar gut microbiomebrain axis linked pathogenesis ndd numerous studies role different micronutrients omega3 fatty acids bioactive polyphenols fruit medicinal plants prevention prediction treatment ndd conducted still far away personalized diet plan individual ndd patients realized largescale cohorts include precise monitoring food intake mapping genetic variants epigenetic data microbiome studies metabolome lipidome transcriptome data neededpmid34422879 pmcpmc8374314 doi103389 fnut2021688086,1.0
family reported outcomes unmet need management patient#39 s disease appraisal literature background persons chronic health condition disability can huge impact quality life qol whole family important impact often ignored literature review aims understand impact patients disease family members across medical specialities appraise existing generic diseasespecific family quality life qol measuresmethodsthe databases medline embase cinhal assia psycinfo scopus searched original articles english measuring impact health conditions patients family members partner using valid instrumentresultsof 114 articles screened 86 met inclusion criteria explored impact relatives disease 14 661 family members mostly parents mothers using 50 different instruments across 18 specialities including neurology oncology dermatology 33 countries including usa china australia studies revealed huge impact patients illness family members appraisal family qol instruments identified 48 instruments 42 disease speciality specific six generic measures five six generics aimed carers children people disability restricted chronic disease generic instrument measures impact condition family members across specialities family reported outcome measure from16 although instruments demonstrated good reliability validity 11 reported responsiveness one reported minimal clinically important differenceconclusionsfamily members qol greatly impacted relatives condition support family members need generic tool offers flexibility brevity use clinical settings across areas medicine from16 tool choice provided robustness demonstrated validation psychometric properties,0.0
familial history autoimmune disorders among patients pediatric multiple sclerosis neurol neuroimmunol neuroinflamm 2021 aug 5 8 5 e1049 doi 101212 nxi0000000000001049 print 2021 sepabstractbackground objective objective study determine whether family members patients pediatric multiple sclerosis ms increased prevalence autoimmune conditions compared controlsmethods data collected pediatric ms casecontrol study risk factors included information various autoimmune diseases family members frequency disorders compared cases controlsresults increased rate autoimmune diseases among family members pediatric ms cases compared controls firstdegree history ms excluded 227 95 ci 171301 p 0001 increased rate ms among seconddegree relatives pediatric ms cases compared controls 347 95 ci 136886 p 0009 ms 264 restricted maternal relatives 637 restricted paternal relativesdiscussion increased rates autoimmune disorders including thyroid disorders ms among families patients pediatric ms suggest shared genetic factors among families children diagnosed pediatric mspmid34353894 doi101212 nxi0000000000001049,0.0
immunometabolic modulatory role naltrexone bv2 microglia cells int j mol sci 2021 aug 5 22 16 8429 doi 103390 ijms22168429abstractbackground naltrexone opioid receptor antagonist commonly used treat opioid alcohol dependence use low dose naltrexone ldn found antiinflammatory properties treatment diseases fibromyalgia crohns disease multiple sclerosis regional pain syndromes related antineuroinflammatory properties mechanism action possibly mediated via tolllike receptor 4 antagonism widely expressed microglial cells aim present study assess immunometabolic effects naltrexone microglia cells vitro conditionsmethods experiments performed bv2 microglial cell line cells treated naltrexone 100 m concentrations corresponding low dose 24 h cell viability assessed every drug dose induce additional activation cells pretreated lps ifn immunofluorescence used analyse classical microglial activation markers inos cd206 seahorse used realtime cellular metabolic assessments mtor activity measured expression major direct downstream target s6k assessed using western blotresults ldn induced shift highly activated proinflammatory phenotype inoshighcd206low quiescent antiinflammatory m2 phenotype inoslowcd206high bv2 microglia cells changes inflammatory profile accompanied cellular metabolic switching based transition high glycolysis mitochondrial oxidative phosphorylation oxphos ldntreated cells able maintain metabolically suppressive phenotype supporting oxphos high oxygen consumption also maintain lower energetic state due lower lactate production metabolic shift induced transition glycolysis mitochondrial oxidative metabolism prominent cells pretreated immunometabolic modulators lps ifn dosedependent manner naltrexone also modulated mtor s6k expression underlies cell metabolic phenotype regulating microglia immune properties adaptationconclusion modulating phenotypic features metabolic switching activated microglia naltrexone found effective powerful tool immunometabolic reprogramming promising novel treatment various neuroinflammatory conditionspmid34445130 doi103390 ijms22168429,0.0
warm sweetened milk twilight immunity alzheimer#39 s disease inflammaging insulin resistance m paratuberculosis immunosenescence front immunol 2021 aug 5 12714179 doi 103389 fimmu2021714179 ecollection 2021abstractthis article prosecutes case zoonotic pathogen mycobacterium avium ss paratuberculosis map precipitant alzheimers disease ad like major neurodegenerative diseases ad core proteinopathy aggregated extracellular amyloid protein plaques intracellular tau protein tangles recognized protein pathologies ad autophagy cellular housekeeping process manages protein quality control recycling cellular metabolism pathogen elimination impaired autophagy cerebral insulin resistance invariant features ad backdrop agerelated lowgrade inflammation inflammaging heightened immune risk immunosenescence infection map subverts glucose metabolism exhausts already exhausted autophagic capacity increasingly variety agents found favorably impact ad agents promote autophagy reduce insulin resistance potpourri therapeutic agents mtor inhibitors sirt1 activators vaccines seemingly random one recognizes agents also suppress intracellular mycobacterial infection zoonotic mycobacterial map causes common fatal enteritis ruminant animals humans exposed map contaminated food products environment enteritis animals called paratuberculosis johnes disease humans putative cause crohns disease beyond crohns map associated increasing number inflammatory autoimmune diseases sarcoidosis blau syndrome autoimmune diabetes autoimmune thyroiditis multiple sclerosis rheumatoid arthritis moreover map associated parkinsons disease india one county extensively studied human bioload map 30 28 000 tested individuals found harbor harbored map article asserts unfolding realization map infection humans 1 widespread presence 2 wideranging zoonosis 3 provides plausible link connecting map adpmid34421917 pmcpmc8375433 doi103389 fimmu2021714179,0.0
association cerebrospinal fluid protein biomarkers outcomes patients traumatic nontraumatic acute brain injury systematic review literature background acute brain injuries associated high mortality rates poor longterm functional outcomes measurement cerebrospinal fluid csf biomarkers patients acute brain injuries may help elucidate pathophysiological pathways involved prognosis patientsmethodswe performed systematic search descriptive review using medline database pubmed interface inception june 29 2021 retrieve observational studies relationship csf concentrations protein biomarkers neurological outcomes reported patients acute brain injury traumatic brain injury subarachnoid hemorrhage acute ischemic stroke status epilepticus postcardiac arrest classified studies according whether biomarker concentrations associated neurological outcomes methodological quality studies evaluated using newcastleottawa quality assessment scaleresultsof 39 studies met criteria 30 reported biomarker concentration associated neurological outcome 9 reported association tbi increased extracellular concentrations biomarkers related neuronal cytoskeletal disruption apoptosis inflammation associated severity acute brain injury early mortality worse longterm functional outcome reduced concentrations protein biomarkers related impaired redox function associated increased risk neurological deficit nontraumatic acute brain injury concentrations csf protein biomarkers related dysregulated inflammation apoptosis associated greater risk vasospasm larger volume brain ischemia high risk bias across studiesconclusionin patients acute brain injury altered csf concentrations protein biomarkers related cytoskeletal damage inflammation apoptosis oxidative stress may predictive worse neurological outcomes,0.0
longitudinal changes tongue thickness tongue pressure neuromuscular disorders background swallowing dysfunction related major cause adverse events indicator shorter survival among patients neuromuscular disorders nmd critical assess swallowing function disease progression however limited tools can easily evaluate swallowing function without using videofluoroscopic videoendoscopic examination evaluated longitudinal changes tongue thickness tt maximum tongue pressure mtp among patients amyotrophic lateral sclerosis als myotonic dystrophy type 1 dm1 duchenne muscular dystrophy dmd methodsbetween 2010 2020 tt mtp measured 21 als 30 dm1 14 dmd patients mean ages 669 445 214 years respectively intervals half year tt measured ultrasonography distance mylohyoid muscle raphe tongue dorsum mtp determined measuring maximum compression small balloon pressing tongue palate examined relationship evaluations patient background swallowing functionresultsmean followup periods 240 months als group 472 months dm1group 611 months dmd group dmd group demonstrated larger first tt groups dm1 group lower first mtp als group als group showed greater average monthly reduction mean tt dm1 group greater monthly reductions mean body weight bw mtp groups significant differences first last bw tt mtp measures found als groupconclusionsthis study suggests als associated rapid degeneration tongue function several years compared dmd dm1,0.0
precision genetic cellular models identify therapies protective er stress cell death dis 2021 aug 5 12 8 770 doi 101038 s41419021040454abstractrare monogenic disorders often share molecular etiologies involved pathogenesis common diseases congenital disorders glycosylation cdg deglycosylation cddg rare pediatric disorders symptoms range mild life threatening biological mechanism shared among cdg cddg well common neurodegenerative diseases alzheimers disease amyotrophic lateral sclerosis endoplasmic reticulum er stress developed isogenic human cellular models two types cdg known cddg discover drugs can alleviate er stress systematic phenotyping confirmed er stress identified elevated autophagy among phenotypes model screened 1049 compounds scored ability correct aberrant morphology model using agnostic cellpainting assay based 300 cellular features primary screen identified multiple compounds able correct morphological phenotypes independent validation shows also correct cellular phenotypes alleviate er stress markers identified model many active compounds associated microtubule dynamics points new therapeutic opportunities rare common disorders presenting er stress alzheimers disease amyotrophic lateral sclerosispmid34354042 doi101038 s41419021040454,0.0
mild knee osteoarthritis predicts dissatisfaction total knee arthroplasty prospective study 186 patients aged 65 years less 2year followup background aimsthe incidence total knee arthroplasty tka increasing especially among younger workingage patients however dissatisfaction rates population higher among older patients aim study assess rates dissatisfaction persistent pain tka evaluate factors predict outcomesmaterial methodsin total 186 patients undergoing unilateral tka aged 65 years less enrolled prospective observational study 2year followup assess outcome visual analogue scales regarding satisfaction persistent pain rest exercise used addition association patients demographics radiographic severity knee osteoarthritis oa patientreported outcome measures proms dissatisfaction persistent pain tested univariate logistic regression analysis mild oa defined kellgrenlawrence kl grade 2 severe oa kl grade 34 furthermore multiple logistic regression analysis also conducted test statistically significant relationsresultsafter 2 years 12 n 23 patients dissatisfied outcome tka 27 n 50 reported persistent pain exercise 10 n 18 rest patients mild knee oa significantly dissatisfied 286 patients severe oa 87 p 0003 younger patients increased risk dissatisfaction persistent pain apart koos quality life poor preoperative koos subscores also predictive outcomesconclusionmild radiographic knee oa main predicting factor dissatisfaction tka thus performing tka patients carefully considered furthermore patients informed increased risk dissatisfaction seems apply younger patients interestingly tka performed patients severe knee oa satisfaction rates seem somewhat higher previously reportedtrial registrationthe study retrospectively registered clinicaltrialsgov registration number nct03233620 28 july 2017,0.0
serum antioligodendrocyte autoantibodies patients multiple sclerosis detected tissuebased immunofluorescence assay front neurol 2021 aug 5 12681980 doi 103389 fneur2021681980 ecollection 2021abstractmultiple sclerosis ms prevalent inflammatory disease central nervous system cns characterized damaged myelin sheaths oligodendrocytes ms patients variable clinical courses disease severities important identify biomarkers predict disease activity severity study assessed frequencies serum autoantibodies mature oligodendrocytes ms patients using tissuebased immunofluorescence assay ifa determine whether antioligodendrocyte antibodies associated clinical features ms patients whether might biomarker assess cns tissue damage ms patients assessed binding serum autoantibodies mouse oligodendrocytes expressing nogoa reliable mature oligodendrocyte marker ifa mouse brain sera 147 ms patients comprising 103 relapsingremitting ms rrms 22 secondary progressive ms spms 22 primary progressive ms ppms patients 38 neuromyelitis optica spectrum disorder nmosd patients 23 inflammatory neurological disorder oind patients 39 healthy controls hcs western blotting wb performed using extracted mouse cerebellum proteins igg antioligodendrocyte antibodypositive ms patients tissuebased ifa showed antioligodendrocyte antibodies positive 3 22 136 ppms 1 22 45 spms patients rrms nmosd oind patients hcs wb demonstrated target cns proteins recognized serum antioligodendrocyte antibodies approximately 110 kda 150 kda compared antioligodendrocyte antibodynegative ms patients ms patients antioligodendrocyte antibodies significantly older time serum sampling scored significantly higher expanded disability status scale multiple sclerosis severity score higher frequency mental disturbance although clinical significance antioligodendrocyte antibodies still unclear low frequency antioligodendrocyte autoantibodies potential biomarkers monitoring disease pathology progression mspmid34421790 pmcpmc8374045 doi103389 fneur2021681980,1.0
predictors cognitive impairment primary agerelated tauopathy autopsy study abstractprimary agerelated tauopathy part form alzheimertype neurofibrillary degeneration occurring absence amyloidbeta plaques part shares features alzheimer disease ad progressive accumulation neurofibrillary tangle pathology medial temporal lobe brain regions progress extensively neocortical regions given restricted pathoanatomical pattern variable symptomatology need reexamine improve upon part neuropathologically assessed staged performed retrospective autopsy study collection n 174 postmortem part brains used logistic regression determine extent set clinical neuropathological features predict cognitive impairment compared braak staging focuses hierarchical neuroanatomical progression ad tau pathology quantitative assessments neurofibrillary burden using computerderived positive pixel counts digitized whole slide images sections stained immunohistochemically antibodies targeting abnormal hyperphosphorylated tau ptau entorhinal region hippocampus also assessed factors affecting cognition including agingrelated tau astrogliopathy artag atrophy found association braak stage cognitive impairment controlling age p 076 contrast ptau burden significantly correlated cognitive impairment even adjusting age p 003 strongest correlate cognitive impairment cerebrovascular disease wellknown risk factor p 00001 features including artag p 003 hippocampal atrophy p 004 also associated contrast sex apoe psychiatric illness education argyrophilic grains incidental lewy bodies findings support hypothesis comorbid pathologies contribute cognitive impairment subjects part quantitative approaches beyond braak staging critical advancing understanding extent agerelated tauopathy changes impact cognitive function,0.0
metabolic modeling single th17 cells reveals regulators autoimmunity cell 2021 jun 29s00928674 21 007005 doi 101016 jcell202105045 online ahead printabstractmetabolism major regulator immune cell function remains difficult study metabolic status individual cells present compass algorithm characterize cellular metabolic states based singlecell rna sequencing flux balance analysis applied compass associate metabolic states t helper 17 th17 functional variability pathogenic potential recovered metabolic switch glycolysis fatty acid oxidation akin known th17 regulatory t cell treg differences validated metabolic assays compass also predicted th17 pathogenicity associated arginine downstream polyamine metabolism indeed polyaminerelated enzyme expression enhanced pathogenic th17 suppressed treg cells chemical genetic perturbation polyamine metabolism inhibited th17 cytokines promoted foxp3 expression remodeled transcriptome epigenome th17 cells toward treglike state vivo perturbations polyamine pathway altered phenotype encephalitogenic t cells attenuated tissue inflammation cns autoimmunitypmid34216539 doi101016 jcell202105045,0.0
alemtuzumab large reallife cohort interim baseline data treatms study front neurol 2021 aug 5 12620758 doi 103389 fneur2021620758 ecollection 2021abstractthe noninterventional longterm study observation treatment alemtuzumab active relapsingremitting ms treatms study collects far largest reallife cohort regarding utilization longterm effectiveness safety alemtuzumab humanized monoclonal antibody directed cell surface glycoprotein cd52 adult patients active relapsingremitting multiple sclerosis rrms interim analysis baseline parameters inclusion noninterventional realworld study alemtuzumab germany including previous multiple sclerosis ms medication utilization ms activity severity duration well comorbidities performed 883 patients 716 women mean age 357 92 years time since first ms symptoms disease duration 80 68 years expanded disability status scale edss 27 18 points range 0075 points number relapses 12 24 months prior inclusion 16 12 22 18 respectively patients 144 treatment naive majority wide spectrum ms diseasemodifying treatments dmts treatment sequences documented overall interferon beta ifnbeta reported frequently 524 followed fingolimod 352 natalizumab 349 glatiramer acetate 289 patients longer disease duration higher edss higher number previous dmts compared pivotal phase 2 3 studies rrms patients starting alemtuzumab treatment longer disease duration realworld conditions variety different treatment sequences final switch alemtuzumab future linking treatment sequences baseline characteristics effectiveness safety outcomes might useful support treatment decisions registered paulehrlichinstitut nis 281pmid34421780 pmcpmc8375470 doi103389 fneur2021620758,0.0
effects combined endurance resistance training women multiple sclerosis randomized controlled study front neurol 2021 aug 5 12698460 doi 103389 fneur2021698460 ecollection 2021abstractpurpose test hypothesis combined resistance endurance training improve muscle strength fatigue depression quality life persons ms methods twentyseven women ms randomly assigned either control con n 13 experimental exp n 14 group participants exp group trained twice week 12 weeks followed 12 weeks detraining con exp groups tested 12 weeks intervention period well 12 weeks training cessation followup measures muscle strength fatigue depression quality life evaluated results significant changes maximal voluntary isometric contraction mvic 1rm leg extension 1rm chest press following intervention period exp group p 005 con group p 005 changes persisted 12 weeks detraining similar findings found fatigue depression physical mental composites quality life conclusion results suggest combined exercise training minimum prevents diseaserelated deterioration muscular performance quality life wellbeing persons mspmid34421801 pmcpmc8374042 doi103389 fneur2021698460,0.0
astroglial microglial purinergic p2x7 receptor major contributor neuroinflammation course multiple sclerosis int j mol sci 2021 aug 5 22 16 8404 doi 103390 ijms22168404abstractmultiple sclerosis ms autoimmune inflammatory disease central nervous system leads progressive disability patients characteristic feature disease presence focal demyelinating lesions accompanied inflammatory reaction interactions autoreactive immune cells glia cells considered central mechanism underlying pathology ms gliamediated inflammatory reaction followed overproduction free radicals generation glutamateinduced excitotoxicity promotes oligodendrocyte injury contributing demyelination subsequent neurodegeneration activation purinergic signaling particular p2x7 receptormediated signaling astrocytes microglia important causative factor pathological processes review discusses role astroglial microglial cells particular glial p2x7 receptors inducing msrelated neuroinflammatory events highlighting importance p2x7rmediated molecular pathways ms pathology identifying receptors potential therapeutic targetpmid34445109 doi103390 ijms22168404,1.0
optical coherence tomography visual evoked potentials prognostic monitoring tools progressive multiple sclerosis front neurosci 2021 aug 5 15692599 doi 103389 fnins2021692599 ecollection 2021abstractunderstanding mechanisms underlying progression developing new treatments progressive multiple sclerosis pms among major challenges field central nervous system cns demyelinating diseases last 10 years also technological advances visual pathways emerged useful platform study processes demyelination remyelination relationship axonal degeneration protection wider availability technological advances optical coherence tomography oct allowed add information structural neuroretinal changes addition functional information provided visual evoked potentials veps present review will address role visual pathway platform assess functional structural damage ms focusing particular role veps oct alone combination prognosis monitoring pmspmid34421520 pmcpmc8374170 doi103389 fnins2021692599,1.0
quality care patients multiple sclerosisa review existing quality indicators front neurol 2021 aug 5 12708723 doi 103389 fneur2021708723 ecollection 2021abstractbackground care patients multiple sclerosis ms calls lifelong guidance treatment results high resource utilization therefore strategies assessment improvement care process crucial quality indicators become widely used instrument determine quality many areas healthcare system currently available sets indicators quality ms care summarized review methods literature search conducted reports include statements quality indicators care people ms determination strength underlying evidence identified publications appropriate criteria prisma agreestatements used prioritization eligible indicators based internal grading initial authors results 465 included records search 6 sources finally identified 3 demonstrating high others medium strength evidence total six reports described 226 quality indicators treatment ms 147 included assessment due scope article among 101 indicators originated reports high strength evidence 6 also high initial internal grading six identified quality indicators describe five important characteristics highquality care ms conclusion search led scientifically evident set six quality indicators assessment care patients ms seen starting points development comprehensive sets quality indicators ms addresses individual objective usepmid34421807 pmcpmc8374044 doi103389 fneur2021708723,0.0
case report situ expression proliferationinducing ligand neuromyelitis optica front neurol 2021 aug 5 12721877 doi 103389 fneur2021721877 ecollection 2021abstracta proliferation inducing ligand april mediates key role generation survival antibodyinducing plasmocytes based april targeted autoimmune diseases including multiple sclerosis ms optic neuritis ms lesions april new cellular target reactive astrocyte mediates immunosuppressive activity analyzed april expression case neuromyelitis optica nmo another autoimmune neurodegenerative disease showing selective aquaporin4 depletion spinal cord complement deposition infiltration polymorphonuclear cells analyzed immunohistochemistry presence aprilproducing cells plasmocytes astrocytes localization secreted april lesion nmo plasmocytes present close aprilproducing cells meninges however main observation april targets reactive astrocytes lesion nmo similarly mspmid34421813 pmcpmc8374102 doi103389 fneur2021721877,0.0
strategies reducing pocket payments health system scoping review background direct outofpocket payments oop among important financing mechanisms many health systems especially developing countries adversely affecting equality leading vulnerable groups poverty therefore scoping review study conducted identify strategies involving oop reduction health systemsmethodsarticles published english strategies related outofpocket payments searched retrieved web science scopus pubmed embase databases january 2000 november 2020 following prisma guidelines result 3710 papers retrieved initially 40 selected fulltext assessmentresultsout 40 papers included 22 55 18 45 study conducted developing developed countries respectively strategies divided four categories based health system functions health system stewardship creating resources health financing mechanisms delivering health servicesas well developing developed countries applied different types strategies reduce oopconclusionthe present review identified strategies affect oop payments according health system functions framework considering importance stewardship creating resources health financing mechanisms delivering health services reducing oop study help policymakers make better decisions reducing oop expenditures,0.0
potential pink1 parkin proteins biomarkers active multiple sclerosis japanese cohort study front immunol 2021 aug 4 12681386 doi 103389 fimmu2021681386 ecollection 2021abstractbackground mitochondrial dysfunction suggested play important role stages multiple sclerosis ms objective determine expression two mitophagyrelated proteins pteninduced kinase 1 pink1 parkin cohort japanese patients different neuroinflammatory disordersmethods protein concentrations measured using commercial elisa paired cerebrospinal fluid csf serum samples patients multiple sclerosis ms neuromyelitis optica spectrum disorders nmosd myelin oligodendrocyte glycoprotein antibody disorders mogad age sexmatched controlsresults csf serum concentrations pink1 higher patients ms patients nmosd p 0004 p 0001 respectively mogad p 0008 p 0011 respectively controls p 0021 p 0002 respectively csf concentrations parkin elevated patients ms comparison controls p 0016 p 005 respectively conclusions study highlighted importance mitophagy ms suggested potential application pink1 parkin biomarkers predict disease activitypmid34421896 pmcpmc8371632 doi103389 fimmu2021681386,1.0
therapeutic response possible biomarkers acute attacks neuromyelitis optica spectrum disorders prospective observational study front immunol 2021 aug 4 12720907 doi 103389 fimmu2021720907 ecollection 2021abstractobjective explore outcomes nmosd attacks investigate serum biomarkers prognosis severitymethod patients nmosd attacks prospectively observationally enrolled january 2019 december 2020 four hospitals guangzhou southern china data collected attack discharge 1 3 6 months acute treatment serum cytokine chemokine neurofilament light chain nfl levels examined onset stageresults one hundred patients nmosd attacks included treatment comprised intravenous methylprednisolone pulse therapy alone ivmp 71 ivmp combined apheresis 8 ivmp combined intravenous immunoglobulin 18 therapies 3 edss scores decreased significantly medium 4 interquartile range 3055 attack 35 3045 discharge 35 2040 1month visit 30 2040 3month visit p001 comparisons remission rate 380 discharge 633 1month visit notably relapse occurred 122 74 patients 6month followup higher levels t helper cell 2 th2 related cytokines including interleukin il 4 il10 il13 il1 receptor antagonist predicted remission 1month visit or933 p004 serum nfl levels correlated positively onset edss scores acutephase nmosd p0001 r2 0487 conclusions outcomes nmosd attacks generally moderate high level serum th2related cytokines predicted remission 1month visit serum nfl may serve biomarker disease severity attackclinical trial registration https clinicaltrialsgov ct2 show nct04101058 identifier nct04101058pmid34421925 pmcpmc8372759 doi103389 fimmu2021720907,0.0
multiple sclerosis lesion segmentation brain mri using inception modules embedded convolutional neural network j healthc eng 2021 aug 4 20214138137 doi 101155 2021 4138137 ecollection 2021abstractmultiple sclerosis ms chronic autoimmune disease forms lesions central nervous system quantitative analysis lesions proved useful clinical trials therapies assessing disease prognosis however efficacy quantitative analyses greatly depends accurately ms lesions identified segmented brain mri usually carried radiologists label 3d mr images slice slice using commonly available segmentation tools however manual practices time consuming error prone circumvent problem several automatic segmentation techniques investigated recent years paper propose new framework automatic brain lesion segmentation employs novel convolutional neural network cnn architecture order segment lesions different sizes pick specific filter size 3 3 5 5 sometimes hard decide filter will work better get best results google net solved problem introducing inception module inception module uses 3 3 5 5 1 1 max pooling filters parallel fashion results show incorporating inception modules cnn improved performance network segmentation ms lesions compared results proposed cnn architecture two loss functions binary cross entropy bce structural similarity index measure ssim using publicly available isbi2015 challenge dataset score 9381 higher human rater bce loss function achievedpmid34484652 pmcpmc8410443 doi101155 2021 4138137,0.0
10years cemara database anddirares network unique resource facilitating research epidemiology developmental disorders france background france ministry health implemented comprehensive program rare diseases rd includes epidemiological program well establishment expert centers clinical care patients rd since 2007 centers entered data patients developmental disorders cemara populationbased registry national online data repository rare diseases cemara web portal descriptive demographic data clinical data chronology medical followup can obtained center address interest ongoing challenges national data collection system 10 years implementation methodssince 2007 clinicians researchers reported minimum dataset mds patient presenting expert center retrospectively analyzed administrative data demographic data care organization diagnoses resultsover 10 years 228 243 rd patients including healthy carriers family members experts denied suspicion rd visited expert center among 167 361 patients affected rd median age 11 years 54 children 46 adults balanced sex ratio 60 882 unaffected relatives median age 37 years majority patients 87 seen year 52 visits diagnostic procedure among 2 869 recorded rare disorders 1 907 665 recorded less 10 patients 802 28 10 100 patients 149 52 100 1 000 patients 11 04 1 000 patients overall 456 individuals diagnosis 67 uncertain diagnosis children mainly referred pediatrician 46 n 55 755 among 121 136 total children referrals adults medical specialist 34 n 14 053 among 41 564 total adult referrals given geographical coverage centers median distance patients home 251 km iqr 63 km642 km conclusionscemara provides unprecedented support epidemiological clinical therapeutic studies field rd researchers can benefit national scope cemara data also focus specific diseases patient subgroups endeavor major collective effort among french rd experts gather largescale data single database provides tremendous potential improve patient care,0.0
bone marrow mesenchymal stem cells promote remyelination spinal cord driving oligodendrocyte progenitor cell differentiation via tnf relbhes1 pathway rat model study 2 5hexanedioneinduced neurotoxicity background nhexane metabolite 2 5hexanedine hd industrial hazardous material chronic hexane exposure causes segmental demyelination peripheral nerves highdose intoxication may also affect central nervous system demyelinating conditions difficult treat stem cell therapy using bone marrow mesenchymal stem cells bmscs promising novel strategy previous study found bmscs promoted motor function recovery rats modeling hexane neurotoxicity work aimed explore underlying mechanisms focused changes spinal cordmethodssprague dawley rats intoxicated hd 400 mg kg day ip 5 weeks bolus bmscs 5 107 cells kg injected via tail vein demyelination remyelination spinal cord bmsc treatment examined microscopically cultured oligodendrocyte progenitor cells opcs incubated hd bmscderived conditional medium bmsccm opc differentiation studied immunostaining morphometric analysis expressional changes hes1 transcription factor negatively regulating opcdifferentiation studied upstream notch1 tnf relb pathways studied key signaling molecules measured correlation neurotrophin ngf tnf also investigated statistical significance evaluated using oneway anova performed using spss 130results demyelinating damage hd remyelination bmscs evidenced electron microscopy lfb staining ng2 mbp immunohistochemistry vitro cultured opcs showed differentiation incubation bmsccm hes1 expression found significantly increased hd decreased bmsc bmsccm change hes1 found however independent notch1 activation dependent tnf relb signaling hd found increase tnf relb hes1 expression bmscs found opposite effect addition recombinant tnf opcs relb overexpression similarly caused upregulation hes1 expression secretion ngf bmsc activation ngf receptor found important suppression tnf production opcsconclusions findings demonstrated bmscs promote remyelination spinal cord hdexposed rats via tnf relbhes1 pathway providing novel insights evaluating exploring therapeutical effect bmscs demyelinating neurodegenerative disease,1.0
genomewide binding profile human re1 silencing transcription factor unveils unique genetic circuitry hippocampus early studies mouse neurodevelopment led discovery re1 silencing transcription factor rest role master repressor neuronal gene expression recently rest reported also repress neuronal genes human adult brain genes found involved proapoptotic pathways repression associated increased rest levels aging found neuroprotective conserved across species however direct genomewide rest binding profiles rest adult brain identified species apply approach mouse human hippocampus find expansion rest binding sites human hippocampus lacking mouse hippocampus human nonneuronal cell types unique human rest binding sites associated genes involved innate immunity processes inflammation signaling basis histology recent public transcriptomic analyses suggest new target genes repressed glia propose increases rest expression midadulthood presage beginning brain aging human rest function evolved protect longevity function neurons glia human brainsignificance statement re1 silencing transcription factor rest repressor served historically model gene regulation mouse neurogenesis recent studies rest also suggested conserved role rest repressor function across lower species aging however direct genomewide studies rest lacking human brain perform first genomewide analysis rest binding human mouse hippocampus majority restoccupied genes human hippocampus distinct mouse restassociated genes unique human hippocampus represent new set related innate immunity inflammation gene dysregulation implicated agingrelated neuropathology alzheimer9s disease,1.0
global warming neurological practice systematic review peerj 2021 aug 4 9e11941 doi 107717 peerj11941 ecollection 2021abstractbackground climate change including global warming will cause poorer global health rising numbers environmental refugees neurological disorders account major share morbidity mortality worldwide global warming also destined alter neurological practice however extent mechanisms unknown aimed collect information effects ambient temperatures human migration epidemiology clinical manifestations neurological disordersmethods searched pubmed scopus 01 2000 12 2020 human studies addressing influence ambient temperatures human migration alzheimers nonalzheimers dementia epilepsy headache migraine multiple sclerosis parkinsons disease stroke tickborne encephalitis model disease neuroinfections protocol preregistered prospero 2020 crd42020147543 results ninetythree studies met inclusion criteria 84 reported ambient temperatures nine migration overall temperature studies suggested relationship increasing temperatures higher mortality morbidity whereas results ambiguous migration studies however unable identify single adequately designed study addressing global warming human migration will change neurological practice still extracted data indicated multiple ways aspects might alter neurological morbidity mortality soonconclusion significant heterogeneity exists across studies respect methodology outcome measures confounders study design including lack data lowincome countries evidence far suggests climate change will affect practice major neurological disorders near future adequately designed studies address issue urgently needed requiring concerted efforts entire neurological communitypmid34430087 pmcpmc8349167 doi107717 peerj11941,0.0
dissociation 2 18f fluoro2deoxydglucose positron emission computed tomography ultrasound clinical assessments patients nonsevere rheumatoid arthritis including remission background inflammation patients joints severe disease activity rheumatoid arthritis ra already visualized quantified 2 18f fluoro2deoxydglucose positron emission computed tomography 18f fdg pet ct little known metabolic status relationship clinical ultrasonography us metrology patients low moderate activity remissionmethodsclinical assessments based 28joint disease activity score das28crp clinical disease activity index cdai 18f fdg pet ct us xray performed 63 ra patients classified remission low moderate severe disease activity groups pet ct visually semiquantitatively analysed determining standardized uptake value suv positive jointsresultsof 1764 joints 211 tender 137 swollen 276 tender swollen 73 tender swollen 205 pet ctpositive 86 uspositive pet us measurements correlated albeit poor concordance positive predictive value pet ct clinical evaluation tender swollen low whereas negative predictive value high highly significant differences found number pet ctpositive joints cumulative suv severe nonsevere patients including remission low moderate activity classified remission nonremission remission low moderate activity moreover correlation pet ct measurements clinical activity positive cdai severe disease group patients remission low moderate activity 2030 joints pet ctnegative remission pet ct us positive different joints pet ctpositive usnegative joints mainly exhibited ra 381 normal 492 osteoarthritic 127 xray patternsconclusions 18f fdg pet ct effective distinguishing patients severely active disease patients nonsevere ra patients including remission pet ct results discordant us clinical observations longitudinal analysis needed explore clinical relevance infraclinical disease,0.0
increased serum neurofilament light thin ganglion cellinner plexiform layer additive risk factors disease activity early multiple sclerosis neurol neuroimmunol neuroinflamm 2021 aug 4 8 5 e1051 doi 101212 nxi0000000000001051 print 2021 sepabstractobjective investigate association combined serum neurofilament light chain snfl retinal optical coherence tomography oct measurements future disease activity patients early multiple sclerosis ms methods analyzed snfl single molecule array technology performed oct measurements prospective cohort 78 patients clinically isolated syndrome early relapsingremitting ms median interquartile range followup 239 233247 months patients grouped abnormal normal snfl levels defined snfl 80th percentile agecorrected reference values likewise patients grouped median split thin thick ganglion cell inner plexiform layer gcip peripapillary retinal nerve fiber layer inner nuclear layer nonoptic neuritis eyes outcome parameters violation evidence disease activity neda3 criteria componentsresults patients abnormal baseline snfl higher risk violating neda3 hazard ratio hr 228 95 ci 127409 p 0006 developing new brain lesion hr 247 95 ci 130469 p 0006 new relapse hr 221 95 ci 097503 p 0058 patients abnormal snfl thin gcip even higher risk neda3 violation hr 361 95 ci 177736 p 42e4 new brain lesion hr 319 95 ci 151676 p 0002 new relapse hr 538 95 ci 1611798 p 0006 patients abnormal snfl aloneconclusions patients early ms presence abnormal snfl thin gcip stronger risk factor future disease activity presence parameter alonepmid34348969 doi101212 nxi0000000000001051,0.0
effects twentyone nutrients phytonutrients cognitive function narrative review j clin transl res 2021 aug 4 7 4 575620 ecollection 2021 aug 26abstractbackground aim brain health becoming important average person number people cognitive impairments alzheimers disease ad rising significantly current food drug administrationapproved pharmacotherapeutics dementia neither cure halt cognitive decline just delay worsening cognitive impairment narrative review summarizes effects nutrients phytonutrients cognitive functionmethods comprehensive literature search pubmed performed find clinical trials humans assessed effects nutrients phytonutrients cognitive function published english 2000 2021 six independent reviewers evaluated articles inclusion reviewresults ninetysix articles summarized narrative review total 21 categories nutrients phytonutrients included ie lipoic acid bacopa monnieri b vitamins cholinergic precursors vitamin d vitamin e ginkgo biloba ginseng lions mane mushroom nacetyl cysteine omega3 fatty acids aloe polysaccharides rhodiola rosea rosemary saffron tart cherries turmeric wild yam withania somnifera xanthines zinc particular noteworthy effects cognition included memory recollection attention intelligence vocabulary recognition response inhibition arousal performance enhancement planning creative thinking reaction time vigilance task switching orientation time place person reading writing comprehension accuracy learning information processing speed executive function mental flexibility daily functioning decrease mental fatigue freedom distractibility nutrients phytonutrients also improved mood contentedness reduced anxiety need caregiving effects completely consistent ubiquitous across patient populations health statuses adverse effects minimal nonexistentconclusion due growing population people cognitive impairment lack effective pharmacotherapeutics prudent afflicted caregivers find alternative treatments narrative review shows many nutrients phytonutrients may promising treating aspects cognitive impairment especially people afflicted adrelevance patients demonstrated number clinical trials healthy adults patients various health challenges eg ad mild cognitive impairment multiple sclerosis parkinsons disease exhibiting wide range severity cognitive defects best served consider multiple nutrients phytonutrients improve aspects cognitive functionpmid34541370 pmcpmc8445631,0.0
quantification cervical cord crosssectional area acquisition vertebra level analysis software multicenter repeatability study traveling healthy volunteer front neurol 2021 aug 4 12693333 doi 103389 fneur2021693333 ecollection 2021abstractbackground considerable spinal cord sc atrophy occurs multiple sclerosis ms mribased techniques sc crosssectional area csa quantification improved time common agreement whether measure single vertebral levels across larger regions whether upper sc csa can reliably measured brain images aim compare multicenter setting three csa measurement methods terms repeatability different anatomical levels analyze agreement measurements performed cervical cord brain mri method one healthy volunteer scanned three times day six sites three scanner vendors using 3t mri protocol including sagittal 3d t1weighted imaging brain covering upper cervical cord sc images analyzed using two semiautomated methods neuroqlab nql active surface model asm fully automated spinal cord toolbox sct different vertebral levels c1c2 c2 3 sc brain images entire cervical cord c1c7 sc images results csa estimates significantly smaller using sct compared nql asm p 0001 regardless cord level interscanner repeatability best c1c7 coefficients variation nql asm sct 04 06 10 respectively csas estimated brain mri slightly lower sc mri p 0006 c1c2 level despite protocol harmonization centers regard image resolution use highcontrast 3d t1weighted sequences variability csa partly scanner dependent probably due differences scanner geometry coil design details mri parameter settings conclusion csa quantification dedicated isotropic sc mri acquired yielded best repeatability entire cervical cord upper part cervical cord use brain mri scans entailed minor loss csa repeatability compared sc mri due systematic differences scanners csa quantification software kept constant within study mri dataset study available publicly test new analysis approachespmid34421797 pmcpmc8371197 doi103389 fneur2021693333,0.0
reviewing significance bloodbrain barrier disruption multiple sclerosis pathology treatment int j mol sci 2021 aug 4 22 16 8370 doi 103390 ijms22168370abstractthe disruption bloodbrain barrier bbb multiple sclerosis ms pathogenesis double effect early onset immune attack later cns selfsustained insideout demyelination neurodegeneration processes review presents characteristics bbb malfunction ms mostly highlights current developments regarding impairment neurovascular unit nvu metabolic mitochondrial dysfunctions bbbs endothelial cells hypoxic hypothesis largely studied agreed upon recently pathologic processes ms hypoxia ms might produced per se nvu malfunction secondary mitochondria dysfunction present three different related terms denominate ongoing neurodegenerative process progressive forms ms indirectly related bbb disruption progression independent relapses evidence disease activity smoldering demyelination silent progression dimethyl fumarate dmf modulators s1p receptor cladribine laquinimode dmts able cross bbb exhibit beneficial direct effects cns different mechanisms action providing hope combined therapy might effective treating ms detailed mechanisms action dmts described also illustrated dedicated images increasing knowledge involvement bbb ms pathology bbb might become therapeutic target ms make impenetrable activated immune cells also allow molecules neuroprotective effect reaching cell target inside cnspmid34445097 doi103390 ijms22168370,1.0
combined neurofilament light optical coherence tomography better predicts multiple sclerosis disease activity either measure alone neurol neuroimmunol neuroinflamm 2021 aug 4 8 5 e1054 doi 101212 nxi0000000000001054 print 2021 sepno abstractpmid34348970 doi101212 nxi0000000000001054,0.0
dendritic cells ccr7 expression important factor autoimmune diseases chronic inflammation cancer int j mol sci 2021 aug 3 22 15 8340 doi 103390 ijms22158340abstractchemotactic cytokineschemokinescontrol immune cell migration process initiation resolution inflammatory conditions part bodys defense system many chemokines also participate pathological processes leading exacerbating inflammatory state characterizing chronic inflammatory diseases review discuss role dendritic cells dcs central chemokine receptor ccr7 initiation sustainment selected chronic inflammatory diseases multiple sclerosis ms rheumatoid arthritis ra psoriasis revisit binary role ccr7 plays combatting progressing cancer discuss ccr7 dcs can harnessed treatment cancer provide necessary background review differential roles natural ligands ccr7 ccl19 ccl21 direct mobilization activated dcs lymphoid organs control formation associated lymphoid tissues alts provide overview dc subsets briefly elaborate different tcell effector types generated upon dct cell priming conclusion promote ccr7 possible target future drugs antagonistic effect reduce inflammation chronic inflammatory diseases agonistic effect boosting reactivation immune system cancer cellbased immune checkpoint inhibitor ici based anticancer therapypmid34361107 doi103390 ijms22158340,0.0
populationbased study estimate survival standardized mortality tuberous sclerosis complex tsc taiwan background tuberous sclerosis complex tsc autosomal dominant disease systemic manifestations can cause significant mortality morbidity populationbased epidemiological studies tsc mortality survival remain scarce though several recent studies provide evidence tsc survival rates high disease prognosis fair patients study aims estimate life expectancy mortality statistics taiwanese tsc patients investigate prognosis associations tsc mortality based demographic variables compare results past literature especially asian patientsmethodstaiwanese national health insurance nhi insurees can obtain catastrophic illness certificates cic certain eligible diseases waive copayments diagnosis two independent physicians cic holders tsc 19972010 identified nhi research database queries enrollment cic acquisition age endpoint end query period death age sex comorbidities obtained patients separated cohorts endpoint age sex age diagnosis analyzed accordinglyresults471 patients 232 male 239 female identified 14 died compared literature patients showed similar demographics age range diagnosis age sex distribution similar manifestations prevalence epilepsy intellectual disability renal disease lower disease prevalence 1 63 290 lower mortality 021 per year nearidentical standardized mortality ratio 499 cumulative mortality 408 found 14 years though mortality plateaued 7 years postenrollment suggesting good overall survival rate comparable previous studies asian patients enrollment age significant prognostic factor lateenrollment age 18 patients higher risk allcause mortality hazard ratio 654 average remaining lifetime significantly lower general population decreased ageconclusionsthis study reports populationbased disease database highlights importance diagnosis age prognosis prediction suggests role renal manifestations mortality furthermore corroborates recent tsc studies asian population terms survival overall physician vigilance early diagnosis careful monitoring beneficial disease outcome patient survival,0.0
traditional chinese medicine nonalcoholic fatty liver disease molecular insights therapeutic perspectives abstractnonalcoholic fatty liver disease nafld become worlds largest chronic liver disease still specific drug treat nafld traditional chinese medicine tcm widely used hepatic diseases centuries asia tcms holistic concept differentiation treatment nafld show advantages treatment complex metabolic disease however multicompounds multitargets big obstacle study tcm summarize pharmacological actions active ingredients frequently used single herbs tcm compounds combined mechanism herbs tcm compounds discussed explore comprehensive effects nafld article aims summarize multiple functions find common ground tcm treatment nafld thus providing enrichment scientific connotation tcm theories promotes exploration tcm therapies nafld,0.0
therapeutic potential celastrol central nervous system disorders highlights vitro vivo approaches molecules 2021 aug 3 26 15 4700 doi 103390 molecules26154700abstractcelastrol abundant compound derived root tripterygium wilfordii largely used traditional chinese medicine shown preclinical clinical efficacy broad range disorders acting via numerous mechanisms including induction expression several neuroprotective factors inhibition cellular apoptosis decrease reactive oxygen species ros given crucial implication pathways pathogenesis central nervous system disorders vitro vivo studies focused attention possible use compound diseases however although available studies reported significant neuroprotective effects celastrol cellular animal models pathological conditions data replicated review aims discuss current vitro vivo lines evidence therapeutic potential celastrol neurodegenerative diseases including alzheimers parkinsons diseases amyotrophic lateral sclerosis huntingtons disease multiple sclerosis cadmiuminduced neurodegeneration well psychiatric disorders psychosis depression vitro vivo studies focused celastrol effects cerebral ischemia ischemic stroke traumatic brain injury epilepsy also describedpmid34361850 doi103390 molecules26154700,1.0
impact drug diversity treatment effectiveness relapsingremitting multiple sclerosis rrms germany 2010 2018 realworld data german neurotransdata multiple sclerosis registry bmj open 2021 aug 3 11 8 e042480 doi 101136 bmjopen2020042480abstractobjective evaluate impact drug diversity treatment effectiveness relapsingremitting multiple sclerosis rrms germanydesign study employs realworld data captured intime clinical visits 67 german neurology outpatient offices neurotransdata ntd multiple sclerosis ms registry 1 january 2010 30 june 2019 including 237 976 visits 17 553 patients rrms adherence clinical effectiveness parameters analysed descriptive statistics timetoevent analysis overall diseasemodifying therapies dmts stratified administration modes injectable oral infusion three time periods compared 20102012 20132015 20162018results 2010 2018 increasing proportion patients rrms treated dmts treatment initiated sooner diagnosis ms introduction oral dmt temporarily induced higher readiness switch comparing three index periods continuous decrease annualised relapse rates less frequent expanded disability status scale edss progression increasing periods without relapse edss worsening stability noevidenceofdiseaseactivity 2 3 criteria lower conversion rates secondary progressive ms oral injectable dmtsconclusion sparked availability new mainly oral dmts rrms treatment effectiveness improved clinically meaningful 2010 2018 similar effects seen injectable oral dmts infusions better personalised treatment allocation many patients likely results indicate overall beneficial effect whole patient ms population result greater selection available dmts benefit beyond headtohead comparative efficacy resulting increased probability readiness individualise ms therapypmid34344670 doi101136 bmjopen2020042480,0.0
small extracellular vesicles menstrual bloodderived mesenchymal stem cells menscs novel therapeutic impetus regenerative medicine abstractmenstrual bloodderived mesenchymal stem cells menscs great potential regenerative medicine mensc received increasing attention owing impressive therapeutic effects preclinical clinical trials however study menscderived small extracellular vesicles evs still initial stages contrast common msc sources eg bone marrow umbilical cord adipose tissue describe basic characteristics biological functions menscderived small evs also demonstrate therapeutic potential small evs fulminant hepatic failure myocardial infarction pulmonary fibrosis prostate cancer cutaneous wound type1 diabetes mellitus aged fertility potential diseases subsequently novel hotspots respect mensc evbased therapy proposed overcome current challenges complexities regarding therapeutic potential mensc evs continue unraveled advances rapidly emerging basic science clinical medicine mensc evbased treatment great potential treating series diseases novel therapeutic strategy regenerative medicine,0.0
cognitive functioning everyday life development questionnaire instrumental activities daily living multiple sclerosis mult scler j exp transl clin 2021 aug 3 7 3 20552173211038027 doi 101177 20552173211038027 ecollection 2021 julsepabstractneuropsychological test scores people ms pwms fully reflect cognitive functioning daily life therefore developed questionnaire based instrumental activities daily living iadl using amsterdam iadlq alzheimers disease starting point fortyeight items evaluated relevance clarity inter national experts n 30 pwms n 61 proxies n 30 consequently four items omitted two items merged seven items added fifty items included iadl questionnaire specific cognitive functioning ms msiadlq future studies warranted assess psychometric properties msiadlqpmid34408904 pmcpmc8365017 doi101177 20552173211038027,0.0
processing progranulin granulins involves multiple lysosomal proteases affected frontotemporal lobar degeneration background progranulin lossoffunction mutations linked frontotemporal lobar degeneration tdp43 positive inclusions ftldtdppgrn progranulin pgrn intracellular secreted proprotein proteolytically cleaved individual granulin peptides increasingly thought contribute ftldtdppgrn disease pathophysiology intracellular pgrn processed granulins endolysosomal compartments therefore better understand conversion intracellular pgrn granulins systematically tested ability different classes endolysosomal proteases process pgrn range ph setpointsresultsin vitro cleavage assays identified multiple enzymes can process human pgrn multi singlegranulin fragments phdependent manner confirmed role cathepsin b cathepsin l pgrn processing showed several previously unidentified lysosomal proteases cathepsins e g k s v able process pgrn distinctive phdependent manners addition demonstrated new role asparagine endopeptidase aep processing pgrn aep unique ability liberate granulin f proprotein brain tissue individuals ftldtdppgrn showed increased pgrn processing granulin f increased aep activity degenerating brain regions regions unaffected diseaseconclusionsthis study demonstrates multiple lysosomal proteases may work concert liberate multigranulin fragments granulins also implicates aep granulin f neurobiology ftldtdppgrn modulating progranulin cleavage granulin production may represent therapeutic strategies ftldpgrn progranulinrelated diseases,0.0
rare variant genetically confirmed tuberous sclerosis complex presenting bilateral renal angiomyolipoma wunderlich syndrome bmj case rep 2021 aug 3 14 8 e243380 doi 101136 bcr2021243380abstracta 28yearold woman came nontraumatic right flank pain hypotension right flank mass multiple hyperpigmented skin papules located centre area face angiomas toes anaemic blood transfusion top aggressive fluid resuscitation abdominal ct showed bilaterally enlarged kidneys fluid collection right perirenal space haemorrhage consideration angiomyolipoma spontaneous perinephric haemorrhage considered tuberous sclerosis complex tsc genetic testing results revealed mutations tsc2 gene consistent diagnosis tsc immediate surgical plans considered time opted discharged medical advice scheduled close outpatient followup patient followed 2 weeks already sirolimus 2 mg daily reported improved overall wellbeing decrease flank mass sizepmid34344650 doi101136 bcr2021243380,0.0
fingolimodassociated central serous chorioretinopathy young girl bmj case rep 2021 aug 3 14 8 e243207 doi 101136 bcr2021243207abstractfingolimod sphingosine1phosphate analogue used treatment multiple sclerosis hereby report rare case fingolimodassociated central serous chorioretinopathy cscr 21yearold woman presented blurring vision right eye 3 weeks initiation oral fingolimod examination bestcorrected visual acuity 20 20 eyes fundus examination revealed shallow serous macular neurosensory detachment right eye confirmed spectral domain optical coherence tomography left eye fundus normal fluorescein angiography showed focal retinal pigment epithelium leak inferior fovea diagnosis fingolimodassociated cscr made oral fingolimod discontinued subsequent followup visits showed partial resolution cscr 2 weeks 1 month complete resolution subretinal fluid 2 months cscr therefore rare adverse effect oral fingolimod treatment baseline eye examination subsequent followup regular intervals recommended patients fingolimodpmid34344648 doi101136 bcr2021243207,0.0
extracellular region bovine milk butyrophilin exhibits closer structural similarity human myelin oligodendrocyte glycoprotein immunological btn family receptors biol chem 2021 aug 2 doi 101515 hsz20210122 online ahead printabstractbovine butyrophilin btn1a1 abundant type transmembrane glycoprotein exposed surface milk fat globules solved crystal structure extracellular region via multiple wavelength anomalous dispersion incorporation selenomethionine bacterially produced protein butyrophilin ectodomain exhibits two subdomains immunoglobulin fold comprising sandwich central disulfide bridge well one nlinked glycosylation fifth cys residue position 193 unpaired prone forming disulfide crosslinks apparent lack ligandbinding site receptor activity suggests function predominantly hydrophilic coat protein prevent coagulation milk fat droplets less structural resemblance members human butyrophilin family btn3a play role immune receptors nterminal bovine butyrophilin subdomain shows surprising similarity human myelin oligodendrocyte glycoprotein protein exposed surface myelin sheaths thus study lends structural support earlier hypotheses correlation consumption cow milk prevalence neurological autoimmune diseases may offer guidance breeding cattle strains express modified butyrophilin showing less immunological crossreactivitypmid34342946 doi101515 hsz20210122,1.0
tuberous sclerosis complex pulmonologist eur respir rev 2021 aug 3 30 161 200348 doi 101183 1600061703482020 print 2021 sep 30abstracttuberous sclerosis complex tsc rare multisystem genetic disorder affecting almost organs sex predominance tsc autosomaldominant inheritance caused heterozygous mutation either tsc1 tsc2 gene leading hyperactivation mammalian target rapamycin mtor tsc associated several pulmonary manifestations including lymphangioleiomyomatosis lam multifocal micronodular pneumocyte hyperplasia mmph chylous effusions lam multisystem disorder characterised cystic destruction lung parenchyma may occur either setting tsc tsclam sporadically slam lam occurs 3040 adult females tsc childbearing age considered nonmalignant metastatic neoplasm unknown origin tsclam generally milder unlike slam may occur males manifests multiple bilateral diffuse thinwalled cysts normal intervening lung parenchyma chest computed tomography lam complicated spontaneous pneumothoraces 70 patients high recurrence rate mtor inhibitors treatment choice lam moderately impaired lung function chylous effusion mmph manifesting multiple solid groundglass nodules highresolution computed tomography usually harmless need treatmentpmid34348978 doi101183 1600061703482020,0.0
radiologically isolated syndrome singlecenter retrospective cohort study abstractbackgroundradiologically isolated syndrome ris likely represents earliest detectable form multiple sclerosis ms recognized risk factors conversion ris clinically definite central nervous system cns demyelinating disease aim characterize new clinical cohort ris analyze previously established risk factors conversion clinically definite diseasemethodsa medical records search performed patients diagnosed ris treating neurologist institution boston usa january 2005 april 2020 demographic data clinical outcomes treatment courses analyzed time first clinical event representing demyelinating disease attack last follow without clinically definite disease calculated person hazard ratios hrs known risk factors conversion ris clinically definite disease calculated using cox proportional hazards modelsresultsof 89 patients median age ris diagnosis 410 years 76 female 8 family history ms 16 autoimmune disorder 66 never smokers 40 bmi 30kg m2 45 spinal cord mri lesions clinically definite disease observed 16 patients 18 followup median time first event 34 years median followup duration full cohort 38 years median edss developed clinically definite disease 125 range 04 recent follow 84 patients longitudinal brain imaging 42 50 new demyelinating lesions gadoliniumenhancing lesions seen 36 patients 43 either baseline n24 followup n12 patients least one t1hypointense lesion n70 83 five patients underwent ultrahigh field mri 7 tesla positive central vein sign two demonstrated leptomeningeal enhancement one found cortical lesions 30 patients susceptibilityweighted imaging acquired routine clinical care 8 least one paramagnetic rim positive lesion previously reported risk factors conversion ms significant age 37 years hr 13 95 confidence interval ci 04735 male sex 15 95 ci 04152 spinal cord lesions 13 04734 nearly onethird ris patients n26 took disease modifying therapy dmt ms median total treatment duration dmt27 years subcohort treated dmt statistically significantly greater number recognized risk factors conversion clinically definite disease compared untreated group p0028 patients took dmt mri changes demonstrating new demyelinating disease activity n16 dimethyl fumarate n9 glatiramer acetate n7 frequently prescribed dmts secondline dmt started 10 patientsconclusionwe characterize new cohort ris patients demonstrating time clinically evident demyelinating disease ris diagnosis approximately 34 years data suggest early use dmt ris may mitigate impact recognized risk factors occurrence clinically evident disease reduce likelihood conversion clinically definite cns demyelinating disease highrisk individuals,1.0
lived experiences adults multiple sclerosis r med j 2013 2021 aug 2 104 6 3842abstractmultiple sclerosis ms chronic often disabling nervous system disease affects 23 million people worldwide research examined lived experiences 46 communitydwelling adults ms conducted five focus groups covered topics diagnosis decisionmaking regarding ms treatment learning paying assistance unmet needs focus group transcripts qualitatively analyzed identify overarching themes participants described ms affects current future physical financial security often feel unheard misunderstood loved ones healthcare providers ms support organizations provide vital collaborative compassionate environment findings reflect importance ms support organizations incorporation social workers ms care teams can foster communication empathy parties provide psycho social treatment link patients needed servicespmid34323878,0.0
expression mir2115p atherosclerosis influence diagnosis prognosis background purpose study evaluate diagnostic prognostic significance mir2115p atherosclerosis detecting expression level serum patients asmethodsa total 85 healthy controls 90 asymptomatic patients participated study expression level mir2115p subjects measured qrtpcr spearman correlation coefficient used evaluate correlation mir2115p crp cimt roc curve established assess diagnostic value mir2115p kaplanmeier survival curve multivariate cox regression analysis used evaluate prognostic significance mir2115p asresultsthe expression levels mir2115p patients significantly lower healthy controls p 0001 mir2115p showed significant negative correlation crp r 0639 p 0001 cimt r 0730 p 0001 auc roc curve 0900 specificity sensitivity 847 789 respectively indicating mir2115p diagnostic value survival analysis showed patients low mir2115p expression likely cardiovascular endpoint events log rank p 0013 conclusionserum mir2115p used new biomarker diagnosis low expression mir2115p associated poor prognosis,0.0
decisionmaking corticosteroids relapses multiple sclerosis development questionnaire based theory planned behaviour abstractbackgroundrelapses multiple sclerosis burdensome events entail potentially lasting loss function people multiple sclerosis consider corticosteroids providing limited benefits risk adverse effectsobjectiveto develop validate questionnaire investigating internal process people multiple sclerosis making decisions corticosteroidsmethodsthe questionnaire structured three domains attitude subjective social norm perceived behavioural control according theory planned behaviour determine action planning development inspired previous questionnaire studying decisions immunotherapy questionnaire tested qualitative thinkaloud interviews n10 feasibility comprehensibility online survey n203 assess construct criterion validityresultsthe 18item questionnaire considered feasible comprehensible predicted intention receive corticosteroids 823 cases subjective social norm impacted intention questionnaire also proved sensitive autonomy preferences people multiple sclerosisconclusionthis study shows questionnaire appropriately explains internal process people multiple sclerosis run considering corticosteroids can used inform developments tailored support people multiple sclerosis making informed decisions relapse management,0.0
identification immuneassociated gene signature immune cell infiltration related overall survival progressive multiple sclerosis abstractbackground delayed diagnosis noneffective treatment contribute shorter life expectancy patients progressive multiple sclerosis pms studies demonstrate key role autoimmunity pms prognostic value immuneassociated factors remains unknown thus study aimed develop immuneassociated gene iag signature related overall survival os conduct immune cell infiltration analysis using pms datamethods differentially expressed iags identified based gene expression profiles gene expression omnibus database iags immport database univariate least absolute shrinkage selection operator lasso penalized cox regression analyses used develop iag signature related os kaplanmeier analyses conducted receiver operating characteristic roc curves generated assess performance additionally differential distribution immune cells identified wilcoxon ranksum tests correlations iags analyzed using spearman correlation analyses moreover univariate multivariate cox regression analyses used identify independent prognostic factors develop prognostic nomogramresults training group consisting 57 pms lesions 52 control tissues obtained batch normalization remove interbatch difference total 206 differentially expressed iags identified 38 associated os thereafter 4iag signature constructed calculate risk score thus classify pms patients high lowrisk groups according mean risk score patients highrisk group lower survival time lowrisk group kaplanmeier plots roc curves demonstrated good performance training internal validation groups additionally five differentially abundant immune cell types identified relationships iags analyzed finally risk score cortical region naive b cells identified independent prognostic factors nomogram incorporating factors developed predict os pmsconclusion novel iag signature may reliable tool assisting neurologists predicting os pms patients clinical settings findings may facilitate personalized treatment provide insights complex mechanism pms,0.0
comparison fatigue sleep quality physical activity quality life psychological status multiple sclerosis patients without covid19 abstractpurposethe study purposed investigate effect covid19 disease fatigue sleep quality physical activity quality life psychological status people msmethodsa total 104 people ms including 46 covid19 disease history enrolled study patients evaluated expanded disability status scale edss fatigue severity scale fss pittsburgh sleep quality index psqi international physical activity questionnaire short form ipaqsf euroqol instrument eq5d3l fear covid19 scale fcv19s coronavirus anxiety scale cas resultspeople ms covid19 positive group significantly lower ipaqtotal score p0014 besides fcv19s scores covid19 positive patients significantly higher p0006 eq5d3l index eq5d3l vas scores higher group covid19 p10021 p20014 respectively fcv19s moderate correlation edss r0362 ipaqtotal moderately associated ms duration edss fss r10471 r20389 r30388 respectively eq5d3l index moderately correlated fss r10404 weakly significant relationship eq5d3l index bmi ms duration psqi cas r10471 r20389 r30388 r40326 respectively hand eq5d3l moderately associated vas edss psqi r10393 r20357 respectively conclusioncovid19 negatively affected people msnulls physical activity coronavirus related fear parameters however causality influence investigated detail,0.0
liver kinase b1 rs9282860 polymorphism risk multiple sclerosis white black americans abstractbackgroundwe previously reported single nucleotide polymorphism snp rs9282860 serine threonine kinase 11 stk11 gene codes liver kinase b1 lkb1 higher prevalence white relapsingremitting multiple sclerosis rrms patients controls however known snp risk factor ms populationsmethodswe assessed prevalence stk11 snp samples collected african american aa persons ms pwms controls multiple veterans affairs va medical centers network academic ms centers genotyping carried using specific taqman assay comparisons snp frequencies made using fishernulls exact test determine significance odds ratios group means compared appropriate ttests based normality variance using spss v27resultsthere significant differences average age first symptom onset age diagnosis disease duration disease severity rrms patients recruited vamcs versus nonvamcs snp prevalent aa white pwms however secondary progressive ms spms patients difference statistically significant aa spms patients higher stk11 snp prevalence controls cohort snp associated older age symptom onset diagnosisconclusionsthe results suggest stk11 snp represents risk factor spms aa patients can influence early onset later conversion spmss events,0.0
patient experience selfperceived biopsychosocial burden people living multiple sclerosis epidemiological survey bpsmuscle study spain abstractbackgroundupdated information selfperceived biopsychosocial burden healthcare experience among people living multiple sclerosis spain scarcewe aim describe selfreported disease experience patients diagnosed ms spain estimate biopsychosocial burdenmethodsmulticentre epidemiological study based crosssectional nationwide survey completed geographically stratified sample ms patients spainresultsa total 490 surveys completed 61 neurology units across spain analysed mean age 437100 years range2172 714 women patients identified relapsingremitting ms 771 819 retained independent mobility patients considered health condition good 394 good 131 mean euroqol questionnaire score 692215 patients expressed high level satisfaction access quality health care however 537 considered sadness depression interfered daily life concerns social support also mentionedconclusionmost people living ms spain consider health condition least good psychological support social protection measures needed insights obtained study may help better manage condition future,0.0
effects watersoluble components atmospheric particulates rare earth mining areas china lung cancer cell cycle background study aims investigate effects water soluble particulate matter wspm viability protein expression profile human lung adenocarcinoma cell a549 bayou obo rare earth mining area explore influence wspm a549 cell cycleresultsit found wspm can inhibit viability a549 cells induce cell arrest g2 m phase compared controls exposure wspm10 wspm25 induced 134 116 proteins differentially expressed a549 cells respectively addition 33 31 differentially expressed proteins confirmed consistent proteomic analysis prominent enrichment ribosomeassociated proteins presented rpl6 rpl13 rpl18a gene expression inhibited a549 cells arrested g1 phase affecting expression cyclin d1 p21 rb1 cyclin a2 cyclin b1 cdc25a cdk2 chek2 e2f1 furthermore la3+ ce3+ nd3+ f wspm also inhibited viability a549 cells 24 h exposure 2 mm naf a549 cells also arrested g2 m phase three compounds effect four compounds affected cell cycle regulatory factors a549 cells mainly focusing effecting expression cdk2 cdk4 rb1 atm tp53 mdm2 genes results consistent wspm exposureconclusionsthese results revealed wspm rare earth mines decreased viability a549 cells induced cell cycle g2 m phase arrest even apoptosis may independent nfb myd88 pathway perceived tlr4 receptor dysfunction cell cycle correlated downexpression ribosomal proteins rps however direct reason a549 cell arrest g2 m phase la3+ ce3+ f probably main toxic substances wspm may regulate a549 cell cycle affecting expression genes mdm2 rb1 atm tp53 e2f1 cdk2 cdk4 results indicate importance research relationship apm lung cancer,0.0
latent tuberculosis infection reactivation patients multiple sclerosis use diseasemodifying therapies systematic review immunomodulators immunosuppressants diseasemodifying therapies dmts can predispose ms patients higher risk infections interfering immune system tuberculosis tb can manifest activated latent forms ltbi can reactivated immunosuppression infection cases virulent strain screening tb done starting treatment cladribine alemtuzumab teriflunomide corticosteroids azathioprine cyclophosphamide methotrexate teriflunomide dimethyl fumarate dmf show higher interference interferongamma release assay igra test results,0.0
antibodymediated autoimmune encephalitis practical approach cleve clin j med 2021 aug 2 88 8 459471 doi 103949 ccjm88a20122abstractantibodymediated autoimmune encephalitis ae heterogeneous group inflammatory central nervous system disorders symptoms typically include subacute progressive neuropsychiatric symptoms associated cognitive dysfunction movement disorders autoimmune seizures diagnosis based objective neurologic dysfunction combination auto antibody testing treatment immunotherapies requires shortterm longterm strategies depending specific syndrome potential relapse paper review key features ae focusing syndromes involving cell surface synaptic proteins share practical approach diagnosis management including common pitfalls associated nonspecific antibody findingspmid34341030 doi103949 ccjm88a20122,0.0
relationship dysphagia respiratory functions anthropometry patients multiple sclerosis abstractbackgroundit known many body systems affected result dysphagia aim study investigate relationship clinical features respiratory functions anthropometric measurements dysphagia patients multiple sclerosis ms methodseventyfive ms patients 50 healthy controls included prospective casecontrol study disability assessed expanded disability status scale edss swallowing assessed questionnaire assessment dysphagia solid liquid total disease respiratory functions demonstrated computerized spirometry device body weight height waist hip midarm circumference measured body mass index body fat percentage calculated relationship parameters disease activity dysphagia investigatedresultsthere 75 ms patients mean age 3840 1127 years 50 6670 female study type dysphagia scores higher ms patients control group p0001 many respiratory function test scores hip circumference lower ms patients however especially low forced expiratory volume1st second fev1 forced vital capacity fvc peak expiratory flow pef values associated disability addition dysphagia scores higher progressive ms patients severe disability high frequency attacks p0001 increased severity dysphagia associated many lower anthropometric measurements heightespecially midarm circumference respiratory function test scoresconclusionms affects swallowing respiratory systems functions associated ms disease activity dysphagia severity associated many anthropometric measurements respiratory functions test scores,0.0
contemporary role mri monitoring management people multiple sclerosis uk abstractbackgroundcompare contemporary use magnetic resonance imaging mri monitoring management people ms uk current consensus guidelinesmethodsthis retrospective multicentre audit clinical practice gathered data 2567 patients ms 25 ms centres across ukresultsroutine monitoring 447 recent clinical relapse 203 common scan indications routine monitoring addition spinal imaging brain showed significant difference disease modifying treatment dmt decision subsequent clinical review approximately 1 5 gadolinium administered scans showed enhancement 1 20 patients gadolinium enhancement evidence radiological disease activity mean interscan intervals relapsingremitting ms routine monitoring 192 months sd 207 wide variation centres 538 patients progressive multifocal leukoencephalopathy pml surveillance met recommended scanning frequency mri protocols demonstrated heterogeneity sequences used diagnostic monitoring pml surveillance scansconclusionsms centres across uk demonstrate varied practice protocols using mri monitor people ms cohort gadolinium use spinal imaging demonstrates limited impact subsequent dmt decisions,0.0
quantitative assessment macropinocytosis mtorc1hyperactive cells using flow cytometry j vis exp 2021 aug 2 174 doi 103791 62793abstractmacropinocytosis highly conserved actindependent endocytic process allows uptake extracellular material including proteins lipids proliferating cells macropinocytosis can deliver extracellular nutrients lysosome processed critical macromolecule building blocks recent studies highlighted dependence multiple cancers macropinocytosis including breast colorectal pancreatic cancer ras mutations thought driver events behind macropinocytosis initiation leading activation cellular anabolic processes via mtorc1 signaling pathway interestingly mtorc1 can also activated macropinocytosis independently ras therefore macropinocytosis represents metabolic vulnerability can leveraged target macropinocytic tumors limiting access nutrients therapeutically tuberous sclerosis complex tsc lymphangioleiomyomatosis lam mtorc1hyperactivation leads enhanced macropinocytosis metabolic reprogramming describe flow cytometrybased protocol assess macropinocytosis mammalian cells quantitatively tsc2deficient mefs employed exhibit aberrant activation mtorc1 shown increased macropinocytosis compared tsc2expressing cells cells treated pharmacologic inhibitors macropinocytosis incubated fluorescently labeled lysinefixable 70 kda dextran fluorescently labeled bovine serum albumin bsa assayed flow cytometry date robust imagebased techniques developed quantitatively assess macropinocytosis tumor cells vitro vivo analysis provides quantitative assessment macropinocytosis multiple experimental conditions complements existing imagebased techniquespmid34398147 doi103791 62793,0.0
delayed access conscious processing multiple sclerosis reduced cortical activation impaired structural connectivity hum brain mapp 2021 apr 7 doi 101002 hbm25440 online ahead printabstractalthough multiple sclerosis ms frequently accompanied visuocognitive impairment especially functional brain mechanisms underlying impairment still well understood consequently used functional mri fmri backward masking task study visual information processing stratifying unconscious conscious ms specifically 30 persons ms pwms 34 healthy controls hc shown target stimuli followed mask presented 8150 ms later compare target reference stimulus retinal integrity via optical coherence tomography optic tract integrity visual evoked potential vep whole brain structural connectivity probabilistic tractography assessed complementary structural brain integrity markers psychophysical level pwms reached conscious access later hc 50 vs 16 ms p 001 delay increased disease duration p 001 37 disability p 001 24 correlate conscious information processing speed symbol digit modality test 07 p 817 association found vep retinal integrity markers moreover pwms characterized decreased brain activation unconscious processing compared hc group differences found conscious processing finally complementary structural brain integrity analysis showed reduced fractional anisotropy corpus callosum impaired connection right insula primary visual areas related delayed conscious access pwms study revealed slowed conscious access visual stimulus material ms complex pattern functional structural alterations coupled unconscious processing delayed conscious access visual stimulus material mspmid33826184 doi101002 hbm25440,0.0
systematic review studies telomere length patients multiple sclerosis aging dis 2021 aug 1 12 5 12721286 doi 1014336 ad20210106 ecollection 2021 augabstracttelomeres protective cap structures end chromosomes essential maintaining genomic stability accelerated telomere shortening related premature cellular senescence shortened telomere lengths tl implicated pathogenesis various chronic immunemediated neurological diseases aimed systematically review current literature association tl measure biological age multiple sclerosis ms comprehensive literature search conducted identify original studies presented data tl samples persons ms quantitative qualitative information extracted articles summarize compare studies total 51 articles screened 7 included review 6 studies average tl analyzed peripheral blood cells whereas one study bone marrowderived cells used four studies reported significantly shorter leukocyte tl least one ms subtype comparison healthy controls p0003 metaanalysis shorter telomeres patients ms found associated independently age greater disability lower brain volume increased relapse rate rapid conversion relapsing progressive ms however remains unclear telomere attrition ms may linked oxidative stress inflammation agerelated disease processes despite studies field substantial evidence association tl ms variability tl appears reflect heterogeneity clinical presentation course investigations large wellcharacterized cohorts warranted detailed studies tl individual chromosomes specific cell types may help gain new insights pathomechanisms mspmid34341708 pmcpmc8279528 doi1014336 ad20210106,0.0
adam10 suppresses demyelination reduces seizure susceptibility cuprizoneinduced demyelination model free radic biol med 2021 may 6s08915849 21 002823 doi 101016 jfreeradbiomed202105001 online ahead printabstractthe metalloproteinase adam10 important amyloid precursor protein app secretase preventing deposit neurotoxic amyloid peptide generating soluble app fragment sapp neurotrophic functions recent studies suggested adam10 also play role pathogenesis inflammatory cns diseases multiple sclerosis ms demyelination hallmarks ms mechanisms involved remain unclear study examined role adam10 might play cuprizoneinduced demyelination model results demonstrated adam10 expression sapp production significantly reduced corpus callosum response cuprizone treatment overexpression adam10 increased sapp production suppressed demyelination well neuroinflammation oxidative stress cuprizoneinduced demyelination model pharmacological inhibition adam10 activity however abrogates protective effect adam10 demyelination neuroinflammation oxidative stress reported cns demyelination may induce seizure activity found overexpression adam10 reduced seizure susceptibility cuprizoneinduced demyelination model suggesting adam10derived sapp suppresses demyelination reduces seizure susceptibility via ameliorating neuroinflammation oxidative stress cuprizoneinduced demyelination modelpmid33965566 doi101016 jfreeradbiomed202105001,1.0
deepmage methylation aging clock developed deep learning aging dis 2021 aug 1 12 5 12521262 doi 1014336 ad20201202 ecollection 2021 augabstractdna methylation aging clocks become invaluable tool biogerontology research since inception 2013 today variety machine learning approaches tested purpose predicting human age based molecularlevel features among deep learning neural networks especially promising approach used construct accurate clocks using blood biochemistry transcriptomics microbiomics datafeats unachieved algorithms article explore deep learning performs dna methylation setting compare current industry standardthe 353 cpg clock published 2013 aging clock presenting deepmage neural network regressor trained 4 930 blood dna methylation profiles 17 studies absolute median error 277 years independent verification set 1 293 samples 15 studies deepmage shows biological relevance assigning higher predicted age people various healthrelated conditions ovarian cancer irritable bowel diseases multiple sclerosispmid34341706 pmcpmc8279523 doi1014336 ad20201202,0.0
low field magnetic stimulation promotes myelin repair cognitive recovery chronic cuprizone mouse model clin exp pharmacol physiol 2021 feb 26 doi 101111 1440168113490 online ahead printabstractbackground multiple sclerosis ms inflammatory demyelinating disease featured neuroinflammation demyelination loss oligodendrocytes cognitive impairment depression common neuropsychiatric symptoms ms poorly managed present interventionsobjective study aimed investigate effects low field magnetic stimulation lfms novel noninvasive neuromodulation technology cognitive impairment depressive symptoms associated ms using mouse model demyelinationmethods c57bl female mice fed 02 cuprizone diet twelve weeks induce chronic demyelinating model followed four weeks cuprizone withdrawal either sham lfms treatmentresults improved cognition depressionlike behavior restored weight gain observed mice lfms treatment immunohistochemical immunoblotting data showed enhanced myelin basic protein mbp myelin oligodendrocyte glycoprotein expressions mog prefrontal cortex mice lfms treatment supporting myelin repair promoted lfms also increased protein expressions mature oligodendrocyte biomarker glutathionestransferase gst addition expression tgf associated receptors elevated lfms treatment implicating pathway responseconclusion results present study revealed lfms neuroprotective effects suggesting lfms potential therapeutic value treating cognitive impairment depression related demyelination disorderspmid33638234 doi101111 1440168113490,1.0
reply multiple manifestations systemic sclerosis affect walk distance j respir crit care med 2021 jun 9 doi 101164 rccm2021041023le online ahead printno abstractpmid34107229 doi101164 rccm2021041023le,0.0
effect covid19 home confinement people multiple sclerosis sleep cardiac autonomic function monitorization physiol behav 2021 mar 19113392 doi 101016 jphysbeh2021113392 online ahead printabstractbackground low sleep quality cardiac autonomic dysfunction poor quality life prevalent symptoms people multiple sclerosis ms addition progression disease symptoms aggravated physical inactivity therefore home confinement due covid19 pandemic restrictions worsen symptoms study aims analyze effect home confinement objective subjective sleep quality cardiac autonomic control based heart rate variability hrv healthrelated quality life people msmethods actigraphic subjective sleep quality karolinska sleep diary ksd hrv polarh7 quality life multiple sclerosis quality life54 measured 2 months home confinement 17 people ms 710 men women age 43411088 years body mass index 2487331 kg m2 expanded disability status scale 285134 au results actigraphic sleep quality sleep efficiency es127 p001 sleep time es081 p001 subjective sleep quality sleep quality es034 p005 sleep comfort es060 p003 ease falling asleep es070 p001 ease waking es087 p001 enough sleep es087 p001 significantly decreased home confinement differences observed hrv quality life variables p013 conclusions home confinement worsened sleep quality cardiac autonomic control quality life people ms data highlight importance implementing home physical training programs population situations similar home confinement occur thus minimizing negative effects physical inactivity associated comorbiditiespmid33753090 doi101016 jphysbeh2021113392,0.0
stopping diseasemodifying therapy relapsing progressive multiple sclerosis curr opin neurol 2021 may 14 doi 101097 wco0000000000000960 online ahead printabstractpurpose review assess reasons considering discontinuation diseasemodifying therapies dmts patients multiple sclerosis ms relevant aspects natural history pathology immunology analyzedrecent findings number retrospective observational studies aggregate indicate stopping dmts may attempted older individuals stable disease prognostic factors identified informing risk recurrence disease activity dmt discontinuationsummary several clinical scenarios provide rationale stop dmts people ms cumulative evidence gathered recently allowing us precisely weigh risks benefits information aids decision processpmid33990101 doi101097 wco0000000000000960,0.0
central vein sign iron rim multiple sclerosis ready clinical use curr opin neurol 2021 apr 28 doi 101097 wco0000000000000946 online ahead printabstractpurpose review summarize recent evidence application susceptibilitybased mri sequences investigate central vein sign cvs iron rim biomarkers improve diagnostic workup multiple sclerosis ms predict disease severityrecent findings cvs specific biomarker ms detectable earliest phase disease threshold 40 lesions cvs can optimal distinguish ms nonms patients iron rim lesions reflecting chronic active lesions develop relapsingremitting ms patients persist progressive ms increase size first years formation stabilize iron rim lesions can distinguish ms nonms patients different ms phenotypes presence least four iron rim lesions associated earlier clinical disability higher prevalence clinically progressive ms severe brain atrophy automated methods cvs iron rim lesion detection development facilitate quantificationsummary assessment cvs iron rim lesions feasible clinical scenario provides mri measures specific ms pathological substrates improving diagnosis prognosis patientspmid33928930 doi101097 wco0000000000000946,0.0
properties reactivity folic acid folate photoproduct 6formylpterin free radic biol med 2021 may 6s08915849 21 002835 doi 101016 jfreeradbiomed202105002 online ahead printabstractfolates vitamin b9 essential components diet gut microbiota omnipresent cells blood folates necessary dna synthesis methylation vital bioprocesses folic acid fa synthetic form folates largely found supplements fortified foods fa folate drugs also extensively used therapeutics therefore continuously exposed pterin derivatives photodegradation products 6formylpterin 6fpt pterin6carboxylic acid ultraviolet radiation two photolytic products generate reactive oxygen species ros responsible cellular oxidative stress 6fpt can exhibit variable pro antioxidative roles depending cell type environment acting cell protector normal cells enhancer druginduced cell death cancer cells rosmodulating capacity 6fpt wellknown whereas intrinsic reactivity much less investigated reviewed properties 6fpt highlighted capacity form covalent adducts rosscavenging drug edaravone used treat stroke amyotrophic lateral sclerosis well implication immune surveillance 6fpt analogue acetyl6fpt function small molecule antigens recognized major histocompatibility complexrelated class ilike molecule mr1 presentation mucosalassociated invariant t mait cells modulators mr1 mait machinery 6fpt derivatives play significant immunoregulatory role different diseases brief review shed light multiple properties cellular activities 6fpt well beyond primary rosgenerating activitypmid33965562 doi101016 jfreeradbiomed202105002,0.0
roles astrocytes response aging alzheimer#39 s disease multiple sclerosis brain res 2021 apr 1147464 doi 101016 jbrainres2021147464 online ahead printabstractastrocytes traditionally recognized multiple roles support brain function however additional changes roles evident response brain diseases review highlight positive negative effects astrocytes response aging alzheimers disease multiple sclerosis summarize data suggesting reactive astrocytes may perform critical functions might relevant etiology conditions particular relate astrocytes effects actions synaptic transmission cognition myelination suggest better understanding astrocyte functions become altered response aging disease will lead appreciation cells useful therapeutic targetspmid33812850 doi101016 jbrainres2021147464,1.0
molecular biochemical aspects salt sodium chloride inflammation immune response reference hypertension type 2 diabetes mellitus abstractobesity insulin resistance type 2 diabetes mellitus t2dm hypertension htn common associated lowgrade systemic inflammation diet genetic factors inflammation immunocytes cytokines play role pathobiology exact role sodium potassium magnesium minerals trace elements vitamins pathogenesis htn t2dm known recent studies showed sodium potassium can modulate oxidative stress inflammation alter autonomic nervous system induce dysfunction innate adaptive immune responses addition action reninangiotensinaldosterone system actions sodium potassium magnesium minerals trace elements vitamins likely secondary action proinflammatory cytokines il6 tnf il17 metabolism essential fatty acids may account involvement pathobiology insulin resistance t2dm htn autoimmune diseases,0.0
multiple manifestations systemic sclerosis affect walk distance j respir crit care med 2021 jun 9 doi 101164 rccm2021040938le online ahead printno abstractpmid34107236 doi101164 rccm2021040938le,0.0
plasma determination neurofilaments biomarkers multiple sclerosis conclusions emotion forum rev neurol 2021 aug 1 73 3 101110 doi 1033588 rn73032020691abstractintroduction management multiple sclerosis ms still need identify biomarkers disease progression clinical subclinical activity among determination neurofilament light chain plasma levels nflpm shown possible correlation clinical course assessment therapeutic response ms patients however determination nflpm overcome several obstacles hinder integration healthcare practice absence normalised values standardised protocolsaim article two main aims review evidence usefulness nfl clinical practice biomarkers neurodegeneration inflammation ms b pool conclusions forum ms experts gathered discuss usefulness applicability nflpm determination spain emotion forum 2020 development nflpm seems particularly useful determining subclinical activity ms offers possibility identifying populations risk developing ms cases radiologically isolated syndrome issues monitoring induction diseasemodifying drugs assessment suboptimal responses withdrawal ineffective diseasemodifying drugs consideredconclusions experts agreed diagnostic prognostic potential nflpm determination usefulness ms can contribute general development techniquepmid34291447 doi1033588 rn73032020691,0.0
redefining use mri patients multiple sclerosis multiple sclerosis common acquired demyelinating disease cns despite many advances understanding pathogenesis multiple sclerosis absence diseasespecific stagespecific biomarkers exists necessitating clinical diagnosis monitoring patients via imaging mri powerful tool differentiating multiple sclerosis various mimics monitoring disease activity,1.0
automated segmentation abnormal tissues medical images j biomed phys eng 2021 aug 1 11 4 415424 doi 1031661 jbpev0i0958 ecollection 2021 augabstractnowadays medical image modalities almost available everywhere modalities bases diagnosis various diseases sensitive specific tissue type usually physicians look abnormalities modalities diagnostic procedures count volume abnormalities important optimal treatment patients segmentation preliminary step measurements also analysis manual segmentation abnormalities cumbersome error prone subjective result automated segmentation abnormal tissue need study representative techniques segmentation abnormal tissues reviewed main focus segmentation multiple sclerosis lesions breast cancer masses lung nodules skin lesions experimental results demonstrate methods based deep learning techniques perform better methods usually based handy feature engineering techniques finally common measures evaluate automated abnormal tissue segmentation methods reportedpmid34458189 pmcpmc8385212 doi1031661 jbpev0i0958,0.0
high prevalence comorbidities diagnosis immigrants multiple sclerosis abstractbackgroundmultiple sclerosis ms associated certain comorbidities general population studies unknown comorbidity may affect immigrants msobjectiveto compare prevalence comorbidities immigrants longterm residents ms diagnosis matched control populations without msmethodswe identified incident ms cases using validated definition applied health administrative data ontario canada 1994 2017 categorized immigrants longterm residents immigrants longterm residents without ms controls matched ms cases 31 sex age geographyresultsthere 1534 immigrants 23 731 longterm residents ms matched 4585 71 193 controls respectively chronic obstructive pulmonary disease copd diabetes hypertension ischemic heart disease migraine epilepsy mood anxiety disorders schizophrenia inflammatory bowel disease ibd rheumatoid arthritis significantly prevalent among immigrants ms compared controls prevalence conditions generally similar comparing immigrants longterm residents ms although copd epilepsy ibd mood anxiety disorders less prevalent immigrantsconclusionimmigrants high prevalence multiple comorbidities ms diagnosis despite healthy immigrant effect clinicians pay close attention identification management comorbidity immigrants ms,0.0
impact swank wahls elimination dietary interventions fatigue quality life relapsingremitting multiple sclerosis waves randomized parallelarm clinical trial mult scler j exp transl clin 2021 jul 31 7 3 20552173211035399 doi 101177 20552173211035399 ecollection 2021 julsepabstractobjective compare effect modified paleolithic elimination wahls lowsaturated fat swank diets relapsingremitting ms rrms methods individuals n 87 rrms randomized swank wahls diets parallel group clinical trial consisting four timepoints 1 runin 2 baseline 3 12weeks 4 24weeksresults 77 participants completed 12 weeks 72 completed 24 weeks 12week change baseline fatigue 094 018 fss 987 193 mfis p 00001 swank 071 024 fss p 0004 1441 222 mfis p 00001 wahls physical msqol scores improved 604 218 p 0006 swank 145 263 p 00001 wahls mental msqol scores improved 113 279 p 00001 wahls swank change 385 263 p 014 neither group showed significant changes 6minute walking distance 12 weeks outcomes maintained improved 24 weeksconclusions diets associated clinically meaningful withingroup reductions fatigue improvements qoltrial registration clinicaltrialsgov identifier nct02914964pmid34377527 pmcpmc8326636 doi101177 20552173211035399,0.0
cerebrospinal fluid inflammatory profile cognitive impairment newly diagnosed multiple sclerosis patients abstractbackgroundthe cerebrospinal fluid csf molecular milieu marker diffuse intrathecal inflammation meninges turn targets grey matter gm multiple sclerosis ms cognitive impairment ci associated brain damage ms often present early people ms pwms objectiveto investigate whether specific csf inflammatory profile associated different degrees ci newly diagnosed pwmsmethodssixtynine pwms 43 healthy controls hcs underwent neuropsychological testing presence levels 57 inflammatory mediators csf assessedresultsapparently cognitively normal acn pwms impaired executive functioning compared hcs performed better pwms mild severe ci mci sci tests csf mediators involving innate immunity immune activation recruitment differentiate acn pwms mci csf mediators related b tcell immunity chemotaxis differentiate acn mci sci cxcl13 molecule differentiated sci mci pwmsconclusionspecific csf molecular patterns reflecting involvement innate adaptive immune responses associated severity ci newly diagnosed pwms,0.0
solid lipid nanoparticles slns advanced drug delivery system targeting brain bbb pharmaceutics 2021 jul 31 13 8 1183 doi 103390 pharmaceutics13081183abstractthe bloodbrain barrier bbb plays vital role protection maintenance homeostasis brain way interesting target interface various types drug delivery specifically context treatment several neuropathological conditions therapeutic agents cross bbb drug toxicity ontarget specificity among limitations associated current neurotherapeutics recent years advances nanodrug delivery enabled carrier system containing active therapeutic drug target signaling pathways pathophysiology closely linked central nervous system cns disorders alzheimers disease ad parkinsons disease pd huntingtons disease hd multiple sclerosis ms brain tumor epilepsy ischemic stroke neurodegeneration present among nano formulations solid lipid nanoparticles slns emerged putative drug carrier system can deliver active therapeutics drugloaded slns across bbb target site brain offering novel approach controlled drug delivery longer circulation time target specificity higher efficacy importantly reducing toxicity biomimetic way paper highlights synthesis application slns novel nontoxic formulation strategy carry cns drugs across bbb improve use therapeutics agents treating major neurological disorders future clinicspmid34452143 doi103390 pharmaceutics13081183,0.0
sarscov2 serology covid19 multiple sclerosis international cohort study abstractbackgroundthe musc19 project italian cohort study open international partners collects data multiple sclerosis ms patients covid19 second wave pandemic serological tests became routinely availableobjectiveto evaluate seroprevalence antisarscov2 antibodies according use diseasemodifying therapy dmt subset patients included musc19 data set undergone serological testmethodswe evaluated association positive serological test results time elapsed since infection onset age sex expanded disability status scale score comorbidities dmt exposure using multivariable logistic modelresultsdata collected 423 patients 345 italy 61 turkey 17 brazil serological test performed followup overall 325 423 tested patients 768 positive serological test multivariate analysis therapy anticd20 significantly associated reduced probability developing antibodies covid19 odds ratio 020 p0002 conclusionpatients ms maintain capacity develop humoral immune response sarscov2 although lesser extent treated anticd20 drugs overall results reassuring respect possibility achieve sufficient immunization vaccination,0.0
openlabel study evaluate biomarkers safety systemic sclerosis patients treated paquinimod abstractobjectivesto evaluate changes diseaserelated biomarkers safety paquinimod oral immunomodulatory compound patients systemic sclerosis ssc methodsin openlabel singlearm multicenter study ssc patients rapidly progressive disease received paquinimod 8 weeks blood skin biopsies collected baseline treatment followup analyses type interferon ifn activity chemokine cc motif ligand 2 ccl2 number myofibroblasts safety paquinimod evaluated throughout studyresultsnine ssc patients enrolled completed study treatment paquinimod 3 mg day 8 weeks treatment reduction type ifn activity plasma one patient elevated baseline ifn activity recorded trend towards reduced ifn activity skin treatment also observed patients serum level ccl2 reduced 7 9 patients paquinimod treatment median reduction 10 number myofibroblasts skin biopsies week 8 compared baseline change modified rodnan skin score quality life detected study reported adverse events aes mild moderate expected common arthralgia n 3 headache n 3 creactive protein crp increaseconclusionsanalysis biomarkers treatment suggest reduced type ifn activity reduced number myofibroblasts lesional skin paquinimod overall well tolerated mild moderate expected aestrial registrationclinicaltrialsgov nct01487551 registered 7 september 2011,0.0
emerging trends focus human gastrointestinal microbiome research 20102021 visualized study background gastrointestinal microbiome important component human body closely related human health disease study describes hotspots human gastrointestinal microbiome research evolution past decade evaluates scientific cooperation network finally predicts fields future development trend using bibliometric analysis visualized studymethodswe searched original articles january 2010 february 2021 scopus database using term gastrointestinal microbiome synonyms citespace used construct country author cooccurrence map conduct journal citation cocitation analysis reference cocitation knowledge map form keywords cooccurrence map clustering knowledge map timeline view keywords burst term mapresulta total 4444 documents published january 2010 february 2021 analysed approximately past decade number articles human gastrointestinal microbiome increased rapidly research topics focus different populations research methods detection methods countries regions world led us studying human gastrointestinal microbiome many research teams close cooperation formed research published extensively microbiology journals clinical medicine journals highly cited articles mainly describe relationship gastrointestinal microorganisms human health disease regarding research emphasis researchers exploration human gastrointestinal microbiome 20112013 relatively macro superficial stage sought determine gastrointestinal microbiome relates humans 2014 2017 increasingly studies conducted determine interaction human gastrointestinal flora various organs systems addition researchers 20182021 focused gastrointestinal microbial community diversity certain types microbesconclusionover time scope research clinical uses gastrointestinal microbiome gradually increased contents gradually deepened developed towards precise level study human gastrointestinal microbiome ongoing research hotspot contributes human health,0.0
brain organoid 3d technology investigating cellular composition interactions human neurological development disease models vitro study human brain physiology including cellular interactions normal disease conditions challenge due complexity unavailability induced pluripotent stem cell ipsc study,0.0
progressive mitochondrial sod1 g93a accumulation causes severe structural metabolic functional aberrations opa1 downregulation mouse model amyotrophic lateral sclerosis int j mol sci 2021 jul 30 22 15 8194 doi 103390 ijms22158194abstractin recent years nonautonomous motor neuron death hypothesis become consolidated behind amyotrophic lateral sclerosis als postulates cells motor neurons participate pathology fact involvement autonomic nervous system fundamental since patients die sudden death become unable compensate cardiorespiratory arrest mitochondria thought play fundamental role physiopathology als compromised multiple als models different cell types also occurs neurodegenerative diseases study aimed uncover mitochondrial alterations sympathoadrenal system mouse model als structural bioenergetic functional perspective disease instauration studied adrenal chromaffin cell mutant sod1g93a mouse presymptomatic symptomatic stages mitochondrial accumulation mutated sod1g93a protein downregulation optic atrophy protein1 opa1 provoke mitochondrial ultrastructure alterations prior onset clinical symptoms changes affect mitochondrial fusion dynamics triggering mitochondrial maturation impairment cristae swelling increased size cristae junctions functional consequences loss mitochondrial membrane potential changes bioenergetics profile reduced maximal respiration spare respiratory capacity mitochondria well enhanced production reactive oxygen species study identifies mitochondrial dynamics regulator opa1 interesting therapeutic target als additionally findings adrenal medulla gland presymptomatic stages highlight relevance sympathetic impairment disease specifically show new sod1g93a toxicity pathways affecting cellular energy metabolism nonmotor neurons offer possible link cell specific metabolic phenotype progression alspmid34360957 doi103390 ijms22158194,0.0
association actinic keratosis rheumatoid arthritis psoriasis nationwide populationbased study korea acta derm venereol 2021 jul 15 doi 102340 000155553877 online ahead printabstractthere epidemiological studies identifying associations systemic inflammatory diseases actinic keratosis study used large nationwide database investigate associations actinic keratosis systemic inflammatory diseases records patients 20 years age newly diagnosed actinic keratosis n 64 659 2012 2017 analysed control population individuals without actinic keratosis matched age sex year claim visited outpatient clinic sampled ratio 11 n 64 659 cohorts analysed presence systemic inflammatory diseases within least 5 years prior diagnosis actinic keratosis patients actinic keratosis exhibited higher odds ratios rheumatoid arthritis 1336 95 confidence interval 95 ci 11611537 psoriasis 1513 95 ci 14351595 compared control group multivariate analysis however proportions behets disease crohns disease ulcerative colitis multiple sclerosis actinic keratosis group statistically significantpmid34263335 doi102340 000155553877,0.0
ocrelizumab treatment multiple sclerosis safety efficacy pharmacology ther clin risk manag 2021 jul 30 17765776 doi 102147 tcrms282390 ecollection 2021abstractthe success selective bcells depleting therapies anticd20 antibodies patients multiple sclerosis ms confirmed bcells critical immune pathogenesis disease ocrelizumab humanized monoclonal antibody selectively targets cd20+ bcells profoundly suppresses acute inflammatory disease activity representing highly effective therapy relapsingremitting multiple sclerosis rrms also first proven therapy able slow disability progression primary progressive multiple sclerosis ppms particularly patients signs acute radiological activity enrolled effectiveness widely demonstrated randomized clinical trials rcts recently confirmed openlabel extension trials review role bcells ms mechanism action ocrelizumab pharmacokinetics pharmacodynamics clinical data supporting use well safety data focus issues related maintenance immunocompetence essential ensure immune response either primary infection vaccination lastly discuss possible role ocrelizumab exit strategy natalizumabtreated patients risk developing multifocal progressive leukoencephalopathy view using ocrelizumab chronically collecting longterm safety data finding strategies minimize adverse events will extremely relevantpmid34354358 pmcpmc8331077 doi102147 tcrms282390,0.0
controversies neurology diagnosis follow therapy multiple sclerosis pathomechanismal approach ideggyogy sz 2021 jul 30 74 708 249255 doi 1018071 isz740249abstractthe clinical boundaries relapsing progressive course multiple sclerosis often indistinct despite variable patterns evolution biological reasons discerning different multiple sclerosis phenotypes indeed primary progressive secondary forms disease share similar pathological features respect extent inflammatory infiltrates axonal damage cortical demyelination data indicating primary progressive multiple sclerosis preceded asymptomatic relapsing remitting phase proposed definition secondary progressive multiple slcerosis attainment least edss 4 required mark transition progressive phase therefore clinical progress can uncovered early phase disease furthermore continuous progression independent relapsing activity commonly observed relapsing remitting phase continuous smouldering process underpins subtle clinical deterioration stands important unmet treatment target concerning cognitive dysfunction patients proinflammatory cytokines associated worse cognition active multiple sclerosis inflammatory milieu also contribute altered mentation relapses therefore long people multiple sclerosis become physically disabled usually acquired hidden disabilities related cognitive impairment silent progression appears relapsing remitting phase associates brain atrophy suggests process underlies secondary progressive multiple sclerosis likely begins far earlier generally recognized supports unitary view multiple sclerosis biologypmid34370413 doi1018071 isz740249,1.0
clinical genetic factors associated anxiety depression breast cancer patients crosssectional study background despite progress assessment treatment breast cancer diagnosed receiving chemotherapy treatment still conceived traumatic experience women develop negative thoughts life death detrimental effects daily physical functioning activities emotional state overall quality life aim study evaluate level anxiety depression among breast cancer patients receiving chemotherapy explore correlation psychological disorders clinical sociodemographic genetic factorsmethodsa crosssectional study conducted among breast cancer patients undergoing intravenous chemotherapy oncology outpatient unit hteldieu de france hospital november 2017june 2019 ethical approval number cehdf1016 patients gave written informed consent completed several validated scales including hospital anxiety depression scale hads assessment anxiety depression sleep quality insomnia cognitive function fatigue pain also evaluated genotyping certain gene polymorphisms clock per2 cry2 oprm1 abcb1 comt drd2 performed using lightcycler roche resultsa total 112 women included prevalence depression 434 562 patients reported anxiety based hads classification multivariable analysis showed higher cognitive scores taking fosaprepitant significantly associated lower depression anxiety scores moreover married compared single also associated lower depression scores whereas higher psqi scores worse sleep quality per2 aa variant genotype compared gg significantly associated higher depression scores finally reporting severe insomnia comt met met genotype significantly associated higher anxiety scoreconclusionsour study demonstrated strong relationship depression scores cognitive impairment sleep quality marital status fosaprepitant intake per2 polymorphism anxiety scores correlated cognitive impairment insomnia severity fosaprepitant intake comt polymorphism association per polymorphism previously reported identification genetic clinical risk factors anxiety depression help clinicians implement individualized management therapy aiming preventing alleviating burden symptoms breast cancer patients hence improving overall quality life,0.0
efficacy ketogenic therapies clinical management people neurodegenerative disease systematic review adv nutr 2021 feb 23nmaa180 doi 101093 advances nmaa180 online ahead printabstractketone bodies potential diseasemodifying activity represent novel therapeutic approach neurodegenerative diseases ndd aim systematic review summarize evaluate evidence application ketogenic therapies dietary exogenous ketogenic agents ndd provide recommendations future research eight databases electronically searched articles reporting controlled trials 4 wk duration induced ketosis elevated serum ketone concentrations people ndd 4498 records identified 17 articles met inclusion criteria total 979 participants including studies mild cognitive impairment mci n 6 multiple sclerosis n 4 alzheimers disease n 5 parkinsons disease n 1 mci secondary parkinsons disease n 1 17 studies 7 randomized doubleblind placebocontrolled trials studies used dietary interventions n 9 followed mediumchain triglycerides n 7 fasting protocol n 1 generally trials 6 wk duration assessed cognition primary outcome studies heterogeneous type severity ndd interventions used outcomes assessed overall 3 17 studies carried low risk bias based available evidence exogenous ketogenic agents may feasible dietary interventions ndd compliance adherence perspective research required confirm recommendations future research include improving exogenous formulations reduce adverse effects exploring interindividual factors affecting responsetotreatment establishing minimum required dose clinically meaningful improvements diseasespecific symptoms cognition motor functionpmid33621313 doi101093 advances nmaa180,0.0
escrt0 subcomplex component hrs hgs master regulator myogenesis via modulation signaling degradation pathways background myogenesis highly regulated process ending formation myotubes precursors skeletal muscle fibers differentiation myoblasts myotubes controlled myogenic regulatory factors mrfs act terminal effectors signaling cascades involved temporal spatial regulation muscle development signaling cascades converge controlled level intracellular trafficking mechanisms myogenesis regulated endosomal machinery trafficking largely unexplored endosomal sorting complex required transport escrt machinery composed four complexes escrt0 escrtiii regulates biogenesis trafficking endosomes well associated signaling degradation pathways investigate role regulating myogenesisresultswe uncovered new function escrt0 hepatocyte growth factorregulated tyrosine kinase substrate hrs hgs component regulation myogenesis hrs depletion strongly impairs differentiation murine human myoblasts c2c12 murine myogenic cell line inhibition differentiation attributed impaired mrf early steps differentiation alteration associated upregulation mek erk signaling pathway downregulation akt2 signaling leading inhibition differentiation myogenic repressors foxo1 well gsk3 also found activated hrs absent inhibition mek erk pathway gsk3 u0126 azakenpaullone compounds respectively significantly restores impaired differentiation observed hrsdepleted cells addition functional autophagy required myogenesis also found strongly inhibitedconclusionswe show first time hrs hgs master regulator modulates myogenesis different levels control trafficking signaling degradation pathways,0.0
different faces tdp43 lowcomplexity domain formation liquid droplets amyloid fibrils int j mol sci 2021 jul 30 22 15 8213 doi 103390 ijms22158213abstracttransactive response dnabinding protein 43 tdp43 nucleic acidbinding protein involved transcription translation regulation noncoding rna processing stress granule assembly aside multiple functions also known signature protein hallmark inclusions amyotrophic lateral sclerosis als frontotemporal lobar degeneration ftld patients tdp43 built four domains lowcomplexity domain lcd become intense research focus brings light possible role tdp43 functions involvement pathogenesis neurodegenerative diseases recent endeavors uncovered distinct biophysical properties tdp43 various circumstances review summarize multiple structural biochemical properties lcd either promoting liquid droplets inducing fibrillar aggregates also revisit roles lcd paraspeckles stress granules cytoplasmic inclusions datepmid34360978 doi103390 ijms22158213,0.0
diagnostic difficulties possibilities nf1like syndromes childhood background neurofibromatosis type 1 nf1 caused heterozygous inactivating pathogenic variants nf1 poor phenotypic expressivity early years life numerous conditions including many tumor predisposition syndromes can mimic appearance collectively termed nf1like syndromes also connected genetic background therefore nf1s clinical diagnostic efficiency childhood difficult commonly completed genetic testingmethodsto estimate number syndromes conditions mimic nf1 compiled extensive search scientific literature test utility nf1s national institutes health nih clinical diagnostic criteria use long time analyzed data 40member pediatric cohort symptoms nf1like syndromes overlapping phenotype performed nf1 genetic test established average age diagnostic suspicion arises facilitate timely identification compiled strongly suggestive phenotypic features anamnestic dataresultsin cohort utility nf1s clinical diagnostic criteria limited sensitivity 80 specificity 30 53 children clinically diagnosed nf1 detectable nf1 pathogenic variation whereas 40 patients without fulfilled clinical criteria tested positive average age first genetic counseling 9 years 40 children referred least one tumor already diagnosed results highlight need improve nf1like syndromes diagnostic efficiency childhood collected extensive spectrum nf1like syndromes help physicians differential diagnosis recommend detailed noninvasive clinical evaluation patients referring clinical geneticistconclusionsearly diagnosis nf1like syndromes can help prevent severe complications appropriate monitoring management propose potential screening diagnostic management strategy based findings recent scientific knowledge,0.0
investigating relationship multiscale perfusion white matter microstructural integrity patients relapsingremitting ms mult scler j exp transl clin 2021 jul 29 7 3 20552173211037002 doi 101177 20552173211037002 ecollection 2021 julsepabstractbackground multiple sclerosis characterized formation central nervous system demyelinating lesions microvasculature inflammationobjective evaluate lesion cerebral perfusion relates white matter microstructural integrity patients rrms using perfusion mri myelinrelated t1weighted t2weighted t1w t2w ratiosmethods fortyeight patients rrms imaged dynamic susceptibility contrast imaging using sage spin gradientecho calculate global capillarysized perfusion parameters including cerebral blood flow cbf volume cbv mean transit time mtt t1w t2w ratios used indirectly assess white matter microstructural integrityresults global perfusion metrics cbf reduced 284 lesion regions interest rois compared normal appearing white matter nawm cbv reduced 259 lesion rois compared nawm mtt increased 129 capillary perfusion metrics via spinecho se cbfse reduced 357 lesion rois compared nawm cbvse reduced 352 lesion rois compared nawm mttse increased 91 capillarylevel cbf correlated 034 p 0024 white matter microstructural integrity lesion roisconclusion study demonstrates lesion perfusion reduced global capillary level capillaryassociated hypoperfusion associated reduced white matter microstructural integrity rrmspmid34377529 pmcpmc8330486 doi101177 20552173211037002,1.0
imaging multiple sclerosis pathology 160 mum isotropic resolution human wholebrain ex vivo magnetic resonance imaging 3 t sci rep 2021 jul 29 11 1 15491 doi 101038 s41598021948911abstractpostmortem magnetic resonance imaging mri fixed healthy diseased human brain facilitates spatial resolutions image quality achievable vivo mri scans though challengingand almost exclusively performed 7 t field strengthdepicting tissue architecture entire brain fine detail invaluable since enables study neuroanatomy uncovers important pathological features neurological disorders objectives present work 1 develop 3d isotropic ultrahighresolution imaging approach human wholebrain ex vivo acquisitions working standard clinical 3 t mri system 2 explore sensitivity specificity concept specific pathoanatomical features multiple sclerosis reconstructed images demonstrate unprecedented resolution soft tissue contrast diseased human brain 3 t thus allowing visualization submillimetric lesions different cortical layers cerebellar cortex well unique cortical lesion characteristics presence incomplete complete iron rims patterns iron accumulation details subpial molecular layer line gennari intrathalamic nuclei also well distinguishablepmid34326420 doi101038 s41598021948911,0.0
pulmonary hypertension systemic sclerosis diagnosis systematic screening prognosis three years followup background systemic sclerosis ssc rare disease presence pulmonary hypertension can determining factor prognosis aim study evaluate diagnosis profile prognosis systemic sclerosis pulmonary hypertension sscph diagnosed systematic screening brazilian population methodsa cohort ssc patients underwent systematic screening sscph patients referred right heart catheterization rhc according transthoracic echocardiogram combination diagnostic tools clinical immunological hemodynamic features prognosis 3 years evaluated resultstwenty patients underwent rhc ssc pulmonary arterial hypertension sscpah common group sscph patients long disease duration high urate levels highly elevated mean pulmonary arterial pressure mpap peripheral vascular resistance pvr hemodynamics patients mpap 20 25 mmhg hemodynamic features intermediate disease patients sscph associated interstitial lung disease sscildph signs vasculopathy hemodynamics patients nosscph survival 1 2 3 years 96 92 92 respectively patients sscph 867 60 533 respectivelyconclusionspatients identified sscpah sscildph screening severe clinical hemodynamic features mortality remains high sscph related bopah sscildph sscpah prognosis better trial registration current controlled trials isrctn 72968188 july 8th 2021 retrospectively registered,0.0
efficacy safety teriflunomide multiple sclerosis across age groups analysis pooled pivotal realworld studies j cent nerv syst dis 2021 jul 29 1311795735211028781 doi 101177 11795735211028781 ecollection 2021abstractbackground evidence suggests efficacy safety diseasemodifying treatments multiple sclerosis may differ age evaluate efficacy safety teriflunomide across age subgroups patients pooled clinical trials realworld studiesmethods post hoc analyses patients received teriflunomide 14 mg pooled phase ii iii temso tower tenere topic core extension studies n 1978 realworld teripro n 928 taurusms n 1126 studies conducted data stratified age study entry 25 25 35 35 45 45 years teripro taurusms additional group 55 years assessedresults pooled core studies teriflunomide reduced annualized relapse rate arr versus placebo across ages unadjusted arrs remained low across age groups pooled extensions 018030 teripro 010035 taurusms 014035 baseline expanded disability status scale scores higher age stable core extension studies mean increases 7 years 25 years +059 25 35 years +046 35 45 years +035 45 years +081 across age groups adverse event ae incidences 784 907 pooled core extension studies teripro 292 377 taurusms serious ae incidences 213 studies pooled phase iii teripro studies lymphocyte count decreases 1 year initiating teriflunomide proportions patients developing lymphopenia small across age groupsconclusions teriflunomide efficacy demonstrated regardless age safety generally consistent across age groupspmid34377047 pmcpmc8330455 doi101177 11795735211028781,0.0
patient treatment characteristics safety outcomes patients relapsingremitting multiple sclerosis treated natalizumab greece results multicenter 5year prospective observational study #39 topics greece#39 mult scler j exp transl clin 2021 jul 29 7 3 20552173211035803 doi 101177 20552173211035803 ecollection 2021 julsepabstractbackground natalizumab highly efficacious treatment relapsingremitting multiple sclerosis rrms objective assess realworld longterm safety natalizumab rrmsmethods multicenter 5year prospective observational study included adults rrms newly initiated natalizumab per approved product label routine care greece safety evaluated collecting serious adverse events saes following study enrollmentresults 19apr2012 18dec2014 304 eligible patients median age natalizumab initiation 380 years median disease duration 62 years enrolled 20 hospitalbased neurologists median treatment duration period 587 months 507 patients discontinued natalizumab mainly due antijcv antibody detection 591 adverse event treatment discontinuation rate 52 sae incidence rate safety data collection period median 487 months 46 common saes infections 10 including 2 cases 07 progressive multifocal leukoencephalopathy pml opportunistic infections pml diagnoses occurred 6267 years natalizumab initiation approximately 2 years first detection antijcv antibody patients incidence rate malignancies 07conclusion realworld settings greece natalizumab displayed acceptable safety profile new safety signals emergingpmid34377528 pmcpmc8327250 doi101177 20552173211035803,0.0
comparison thalamus basal ganglia signs multiple sclerosis primary angiitis central nervous system exploratory study front neurol 2021 jul 29 12513253 doi 103389 fneur2021513253 ecollection 2021abstractbased symptoms especially affecting small vessels difficult distinguish multiple sclerosis ms primary angiitis central nervous system pacns magnetic resonance imaging mri helps understand characteristics deep gray matter lesions dgml ms pacns aimed compare mri characteristics thalamus basal ganglia lesions relapsingremitting ms pacns study 49 relapsingremitting ms patients 16 pacns mriconfirmed thalamus basal ganglia lesions enrolled among dgmls basal ganglia putamen significantly higher p 0037 involvement pacns ms importantly larger lesion sizes thalamus helps distinguish pacns 124 43 mm ms 79 37 mm p 0006 using lesions basal ganglia researchers unable differentiate two disorders presently study shows mri performances deep gray matter differ ms pacnspmid34393963 pmcpmc8358104 doi103389 fneur2021513253,0.0
effects vitamin d dexamethasone lymphocyte proportions associations serum concentrations 25hydroxyvitamin d 3 vitro patients multiple sclerosis neuromyelitis optica spectrum disorder front immunol 2021 jul 29 12677041 doi 103389 fimmu2021677041 ecollection 2021abstractbackground clear associations found vitamin d deficiency several autoimmune diseases including multiple sclerosis ms however benefits vitamin d supplementation disease management remain matter debateobjective methods patients ms n12 neuromyelitis optica spectrum disorder nmosd n12 enrolled along 15 healthy controls changes lymphocyte subset proportions stimulation peripheral blood mononuclear cells pbmcs active form vitamin d 1 25dihydroxyvitamin d3 1 25 oh 2d3 correlations serum concentrations vitamin d precursor 25hydroxyvitamin d3 serum 25 oh d3 explored impact 1 25 oh 2d3 stimulation expression vitamindresponsive genes immune cells also investigatedresults ms nmosd stimulation pbmcs 1 25 oh 2d3 followed steroid suppressed proliferation total lymphocytes t cells ratio cd19+cd27+ memory b cells bmem b cells stimulation 1 25 oh 2d3 negatively correlated serum 25 oh d3 ms spearmans 0594 p0042 positively correlated nmosd pearsons r 0739 p0006 however relationship ratio bmem cd19+cd24+cd38+ regulatory b cells serum 25 oh d3 either ms nmosd addition level 1 25 oh 2d3induced cyp24a1 mrna expression pbmcs significantly negatively correlated serum 25 oh d3 ct r0744 p0014 msconclusion findings suggest beneficial impact stimulation pbmcs vitamin d followed steroid tcell population association patient serum 25 oh d3 proportion bmem immunecell stimulation differed ms nmosd investigations warranted larger patient populationspmid34394078 pmcpmc8358328 doi103389 fimmu2021677041,0.0
fatty acid synthesis glial cells cns int j mol sci 2021 jul 29 22 15 8159 doi 103390 ijms22158159abstractfatty acids fas crucial importance brain homeostasis neural function glia cells support high demand fas central nervous system cns needs proper functioning additionally fas can modulate inflammation direct cns repair thereby contributing brain pathologies alzheimers disease multiple sclerosis intervention strategies targeting fa synthesis glia represents potential therapeutic opportunity several cns diseasespmid34360931 doi103390 ijms22158159,0.0
quantifying patients perspective neuromyelitis optica spectrum disorder psychometric properties symptomscreen questionnaire plos one 2021 jul 29 16 7 e0255317 doi 101371 journalpone0255317 ecollection 2021abstractbackground assessment selfreported outcomes neuromyelitis optica spectrum disorder nmosd limited lack validated diseasespecific measures symptomscreen syms patientreported questionnaire measuring symptom severity different domains affected multiple sclerosis ms thoroughly evaluated nmosd aim study assess psychometric properties syms sample patients nmosdmethods noninterventional crosssectional study adult subjects nmosd wingerchuk 2015 criteria conducted 13 neuroimmunology clinics applying syms nonparametric item response theory procedure mokken analysis performed assess underlying dimensional structure scalability items overall questionnaire analyses performed r v403 using mokken libraryresults total 70 patients studied mean age 475 15 years 80 female mean expanded disability status scale score 30 interquartile range 15 45 symptom severity low median syms score 190 interquartile range 100 320 syms showed robust internal reliability cronbachs alpha 090 95 confidence interval 086 093 behaved unidimensional scale items showing scalability coefficients 030 overall syms scalability 045 conforming medium scale according mokkens criteria fatigue body pain domains highest scalability coefficients syms associated disability rho 0586 physical psychological quality life rho 0856 0696 respectively conclusions syms shows appropriate psychometric characteristics may constitute valuable easytoimplement option measure symptom severity patients nmosdpmid34324586 doi101371 journalpone0255317,0.0
extracellular vesicles blood sources effects applications int j mol sci 2021 jul 29 22 15 8163 doi 103390 ijms22158163abstractextracellular vesicles evs important players intercellular communication evs secreted almost cell types can transfer information nearby distant cells highly abundant body fluids review describe general characteristics evs well isolation characterization approaches focus one relevant sources evs blood indeed apart evs secreted blood cells evs diverse origins travel bloodstream present numerous types evs found circulation besides implications bloodderived evs physiological pathological processes summarized highlighting potential biomarkers diagnosis treatment monitoring prognosis several diseases also indicators physiological modifications finally applications evs introduced circulatory system discussed describe use evs distinct origins naturally produced engineered autologous allogeneic even different species effects introduced circulation therefore present work provides comprehensive overview components effects applications evs bloodpmid34360924 doi103390 ijms22158163,0.0
effects dvddelivered randomized controlled physical activity intervention functional health cancer survivors background supervised physical activity interventions improve functional health cancer survivorship remain costly inaccessible many previously reported benefits dvddelivered physical activity program flextoba older adults secondary analysis intervention effects among cancer survivors original samplemethodslow active older adults selfreported history cancer n 46 m time since diagnosis 107 94 years participated 6month homebased physical activity intervention participants randomized either dvddelivered physical activity program focused flexibility toning balance flextoba n 22 attentional control condition n 24 physical function assessed short physical performance battery sppb baseline end intervention 12 24 months baselineresultsrepeated measures linear mixed models indicated significant grouptime interaction sppb total score 114 p 0048 driven improved function baseline six months flextoba group intervention group also improved balance 056 p 0041 compared controls similar trends emerged sppb total score followup grouptime interaction 0 12 months approached significance 097 p 0089 significant 0 24 months 184 p 0012 significant interactions emerged outcomes ps 011 conclusionsa dvddelivered physical activity intervention designed cancerfree older adults capable eliciting maintaining clinically meaningful functional improvements subgroup cancer survivors similar effects original full sample findings inform dissemination evidencebased physical activity programs survivorshiptrial registrationclinicaltrialsgovnct01030419 registered 11 december 2009,0.0
mobile attention bias modification training digital health solution managing distress multiple sclerosis pilot study pediatric onset front neurol 2021 jul 28 12719090 doi 103389 fneur2021719090 ecollection 2021abstractintroduction emotional health important dimension care patients living pediatric onset multiple sclerosis poms options available stress anxiety reduction high burden interventions requiring regular person onsite visits treatment less feasible attention bias modification training abmt effective anxiety reduction adult adolescent populations tested feasibility preliminary efficacy abmt delivered mobile gamified version digital emotional health tool patients poms methods participants poms consecutively recruited nyu langone pediatric ms care center enrolled complete 1month intervention use personal zen abmt app mobile personal device feasibility evaluated use 1month intervention efficacy measured changes depression anxiety affect results total n 35 patients poms enrolled study m age 177 sd 22 years range 1423 feasibility criteria met 74 completing full intervention time 100 sample completing least 50 targeted intervention use initial efficacy found reduction negative affect baseline intervention end m 2288 sd 995 vs m 1956 sd 737 t 33 247 p 0019 anxiety also significantly decreased pre postintervention adults m 1182 sd 990 vs m 729 sd 717 t 16 388 p 0001 youth m 5114 sd 1966 vs m 4086 sd 2748 t 13 317 p 0007 conclusion mobile abmt personal zen app feasible accessible digital emotional health tool patients poms may broader application managing distress across chronic neurological conditionspmid34393986 pmcpmc8355356 doi103389 fneur2021719090,0.0
balo#39 s concentric sclerosis monophasic course report 2 cases ann med surg lond 2021 jul 28 68102602 doi 101016 jamsu2021102602 ecollection 2021 augabstractintroduction balos concentric sclerosis bcs rare demyelinating disease sometimes considered variant multiple sclerosis characterized acute subacute neurological symptoms characteristic mri onionlike white matter lesions bcs wide range presentations mostly selflimiting steroids indicated patients aggressive diseasecase presentation report 2 cases bcs monophasic course strokelike symptoms single periventricular concentric lamella onionlike appearance mri without inflammatory reaction csf treated corticosteroids achieving clinical improvement without neurological deficit relapse following yearsclinical discussion number cases bcs described literature show marked recovery early diagnosis treatment steroidsconclusion bcs appears good prognosis treated early diagnosis steroidspmid34401123 pmcpmc8347801 doi101016 jamsu2021102602,1.0
impact diseasemodifying treatments multiple sclerosis antisarscov2 antibodies observational study neurol neuroimmunol neuroinflamm 2021 jul 28 8 5 e1055 doi 101212 nxi0000000000001055 print 2021 sepabstractobjective compare humoral response severe acute respiratory syndrome coronavirus 2 sarscov2 infection patients multiple sclerosis ms receiving different diseasemodifying treatments dmts methods patients ms coronavirus disease 2019 covid19 available antisarscov2 serology included primary endpoint antisarscov2 immunoglobulin g igg index multivariate analysis adjusted covid19 severity sarscov2 pcr result time covid19 onset serologyresults included 61 patients available igg index igg index lower patients fingolimod anticd20 monoclonal antibodies compared patients without treatment p 001 patients interferon 1a glatiramer p 001 patients another dmt p 001 igg index correlated time covid19 onset serology r 0296 0510 00477 p 002 conclusions humoral response covid19 lower patients ms fingolimod anticd20 mab patients therefore risk recurrent infection benefit antisarscov2 vaccination humoral response vaccination delay vaccination need evaluatedclassification evidence study provides class iv evidence patients treated fingolimod anticd20 monoclonal antibodies ms lower humoral response covid19 compared patients without dmts another dmtspmid34321333 doi101212 nxi0000000000001055,1.0
covid19 vaccine hesitancy multiple sclerosis crosssectional survey abstractbackgroundvaccine willingness among people living multiple sclerosis pwms requires assessment following approval first covid19 vaccines since remains uncertainty multiple aspects covid19 vaccination immunosuppressed patientsobjectiveto understand covid19 influenza vaccine willingness associations among pwms following approval first two mrna covid19 vaccinesmethodsa survey distributed pwms via online platform december 2020 february 2021 logistic regression models constructed determine relationship 1 covid19 2 influenza vaccination willingness demographic clinical characteristicsresultsof 701 responding pwms 766 covid19 vaccine willing covid19 vaccine willingness significantly associated influenza vaccine willingness p 0001 multivariable models older age increased odds covid19 influenza vaccine willingness odds ratios ors 1 race decreased odds covid19 influenza vaccine willingness ors 1 higher functional disability decreased odds covid19 vaccine willingness 088 95 confidence interval 080096 prevalent vaccinerelated concerns include safety n 244 efficacy n 122 conclusionour findings identify demographic clinical factors well concerns influencing vaccine hesitancy pwms results may inform effective public health interventions improve vaccine acceptability atrisk group,0.0
use multidomain patient reported outcome measures detecting clinical disease progression multiple sclerosis abstractobjectivepatient reported outcome measures proms especially relevant times increased interest telehealth little known relation functional disability measuresmethodswe assessed 248 people ms baseline 5years followup investigated crosssectional longitudinal correlations changes guynulls neurological disability scale gnds physical part multiple sclerosis impact scale msis29 expanded disability status scale edss 9hole peg test 9hpt timed 25foot walk t25fw resultsthe strongest crosssectional correlations found gnds edss complete cohort r066 p 001 n248 well progressive patients r072 p 001 n35 gnds t25fw progressive ms r064 p 001 n34 longitudinal correlations poor except changes leg domain gnds relation t25fw changes progressive ms r068 p 001 n26 majority cases clinically significant deterioration edss also resulted clinically significant worsening gdns msisconclusionboth proms correlate well physical disability outcomes seem suitable detecting changes lower limb function progressive ms gnds higher agreement edss progression msisphysical,0.0
rituximab versus mitoxantrone comparing effectiveness safety advanced relapsing multiple sclerosis ther adv chronic dis 2021 jul 28 1220406223211024366 doi 101177 20406223211024366 ecollection 2021abstractbackground rituximab rtx cd20 depleting agent frequently used offlabel treatment multiple sclerosis ms mitoxantrone mtx approved albeit rarely used active relapsing ms rms however observational data comparing rtx mtx effectiveness safety scarceobjective aimed compare effectiveness safety mtx rtx patients active rmsmethods combined retrospective clinical data three ms centers selected patients received least one infusion rtx mtx least 6month clinical followup available treatment groups compared propensity score ps adjusted regression inverse psweighted generalized estimated equation models regarding disability progression relapse activity adverse events aes results included 292 rms patients mean age 418 years 716 female received rtx 119 patients mean age 368 years 748 female mtx 173 patients mean age 453 years 694 female using ps methods find significant effect favoring rtx mtx treatment regarding probability disability worsening relapse occurrence however rtx treatment associated significantly lower probability severe aes aesconclusions rtx shows comparable effectiveness favorable safety profile compared mtx active rmspmid34377385 pmcpmc8323410 doi101177 20406223211024366,0.0
flood control milkderived extracellular vesicles can help improve intestinal barrier function break gutjoint axis rheumatoid arthritis front immunol 2021 jul 28 12703277 doi 103389 fimmu2021703277 ecollection 2021abstractmany studies provided compelling evidence extracellular vesicles evs involved regulation immune response acting enhancers dampeners immune system depending source type vesicle research including ours shown antiinflammatory effects milkderived evs using human breast milk well bovine colostrum storebought pasteurized cow milk vitro systems well therapeutically animal models although completely elucidated proteins mirnas within milkderived evs contribute immunosuppressive capacities one proposed mechanism action evs via modulation crosstalk intestinal microbiome host health increasing awareness gut plays important role many inflammatory diseases enhanced intestinal leakiness dysbiosis gut microbiome bowel inflammation associated intestinal diseases like colitis crohns disease also characteristic systemic inflammatory diseases lupus multiple sclerosis rheumatoid arthritis ra strategies target gut especially microbiome investigation hold promise therapeutic intervention diseases use milkderived evs either standalone drug drug carrier often suggested recent years several research groups studied tolerance safety using milkderived evs animal models due composition milkderived evs highly biocompatible limited immunogenicity even cross species furthermore demonstrated milkderived evs taken gastrointestinal tract stay intact absorption indicating excellent stability characteristics make milkderived evs suitable drug carriers also evs already substantial immunoregulatory function even without loading vesicles can act therapeutics review will address immunomodulating capacity milkderived evs discuss potential therapy ra patientsreview criteria search terms extracellular vesicles exosomes microvesicles rheumatoid arthritis gutjoint axis milk experimental arthritis used englishlanguage full text papers published 1980 2021 identified pubmed google scholar databases reference list paper searched identify additional relevant articlespmid34394100 pmcpmc8356634 doi103389 fimmu2021703277,0.0
trinuclear calcium site c2 domain pkc prone lithium attack acs omega 2021 jul 28 6 31 2065720666 doi 101021 acsomega1c02882 ecollection 2021 aug 10abstractlithium li+ firstline therapy bipolar disorder candidate drug various diseases amyotrophic lateral sclerosis multiple sclerosis stroke despite captivating subject many studies mechanism lithiums therapeutic action remains unclear date shown li+ competes mg2+ na+ normalize activity inositol neurotransmitterrelated signaling proteins respectively furthermore li+ may cobind mg2+loaded adenosine guanosine triphosphate alter complexs susceptibility hydrolysis mediate cellular signaling bipolar disorder patients exhibit abnormally high cytosolic ca2+ levels protein kinase c pkc hyperactivity can downregulated longterm li+ treatment however possibility monovalent li+ displace bulkier divalent ca2+ inhibit pkc activity considered using density functional theory calculations combined continuum dielectric methods show li+ may displace native dication positively charged trinuclear site c2 domain cytosolic pkc affect membranedocking ability cytosolic pkc reduce abnormally high membraneassociated active pkc levels thus downregulating pkc hyperactivity found bipolar patientspmid34396011 pmcpmc8359144 doi101021 acsomega1c02882,0.0
increased chitotriosidase 1 concentration following nusinersen treatment spinal muscular atrophy background studies regarding impact neuro inflammation inflammatory response following repetitive intrathecally administered antisense oligonucleotides aso 5qassociated spinal muscular atrophy sma sparse increased risk hydrocephalus untreated sma patients marginal significant increase serum csf albumin ratio qalb rare cases communicating hydrocephalus nusinersen treatment reported confirms unmet need inflammatory biomarker sma aim study investigate neuro inflammatory marker chitotriosidase 1 chit1 sma patients following treatment aso nusinersen methodsin prospective multicenter observational study studied csf chit1 concentrations 58 adult 21 pediatric patients sma type 1 2 3 treatment initiation comparison age sexmatched controls investigated dynamics nusinersen treatment concurrently motor performance disease severity assessedresultschit1 concentrations elevated treatmentnave sma patients compared controls less pronounced described neurodegenerative diseases amyotrophic lateral sclerosis chit1 concentration correlate disease severity distinguish clinical subtypes chit1 concentration show significant increase nusinersen treatment unrelated clinical response nusinersen therapyconclusionschit1 elevation treatmentnave sma patients indicates involvement neuro inflammation sma lacking correlation chit1 concentration disease severity argues use marker disease progression observed chit1 increase nusinersen treatment may indicate immune responselike offtarget reaction since antisense oligonucleotides establishing approach treatment neurodegenerative diseases observation needs evaluated,0.0
day life qualitative study clinical decisionmaking uptake neurorehabilitation technology background neurorehabilitation engineering faces numerous challenges translating new technologies unclear challenges limiting aim improve understanding rehabilitation therapists realtime decisionmaking processes use rehabilitation technology rt clinical treatmentmethodswe used phenomenological qualitative approach three ots two pts employed major technologyencouraging rehabilitation hospital wrote vignettes written prompt describing rt use decisions treatment sessions nine patients 4 stroke 2 traumatic brain injury 1 spinal cord injury 1 multiple sclerosis coded vignettes using deductive qualitative analysis 17 constructs derived rt literature consolidated framework implementation research cfir data synthesized using summative content analysisresultsof constructs recorded five prominent cfir determinants relative advantage ii personal attributes patients iii clinician knowledge beliefs device intervention iv complexity devices including time setup v organizational readiness implement therapists characterized candidate rt relative disadvantage compared conventional treatment due lack relevance functional training rt design also often failed consider multifaceted personal attributes patients including diagnoses goals physical cognitive limitations clinicians comfort rt increased previous training decreased perceived complexity rt finally therapists limited time gather setup use rtconclusionsdespite decades design work aimed creating clinically useful rt many lack compatibility clinical translation needs inpatient neurologic rehabilitation new rt continue impede immediacy versatility functionality handson therapy mediated treatment simple everyday objects,0.0
generic outcome assessment mobility capacity neurorehabilitation measurement properties de morton mobility index background mobility capacity key outcome domain neurorehabilitation de morton mobility index demmi established generic outcome assessment mobility capacity older patients promising use neurorehabilitation aim study examine measurement properties demmi rehabilitation inpatients neurological conditionsmethodscrosssectional study including mixed sample adult inpatients neurorehabilitation hospital structural validity unidimensionality measurement invariance rasch analysis construct validity internal consistency reliability interrater reliability demmi scale range 0100 points established minimal detectable change 95 limits agreement possible floor ceiling effects calculated indicate interpretabilityresultswe analyzed validity n 348 reliability n 133 two samples samples majority participants subacute stroke parkinsons diseaserasch analysis indicated unidimensionality overall fit model chisquare 594 p 0074 relevant measurement invariance disease group hypothesesbased correlation analyses demmi functional outcome assessments showed sufficient construct validity internal consistency reliability cronbachs alpha 094 interrater reliability intraclass correlation coefficient 094 95 confidence interval 091095 sufficient minimal detectable change 90 confidence 150 points limits agreement 39 floor ceiling effects observedconclusionsresults indicate sufficient measurement properties demmi rehabilitation inpatients neurological conditions demmi can used generic outcome assessment mobility capacity neurorehabilitationtrial registrationgerman clinical trials register drks00004681 registered may 6 2013,1.0
sexual behaviour human papillomavirus vaccine qualitative study adolescents parents andalusia background human papillomavirus hpv one common sexually transmitted infections can prevented vaccination purpose study gain better understanding analysing interview responses adolescents parents adolescent sexual behaviour approached families widespread knowledge hpv andalusia autonomous region lowest vaccination rate spain well learn interviewees position regarding vaccinationmethodsa qualitative study means 15 focus groups adolescents n 137 aged 1417 years five focus groups parents children ages n 37 conducted provinces granada seville jan andalusia spain audio data transcribed verbatim coded analysed thematically using nvivo10 softwareresultsthere three major results 1 lack communication adolescents parents regarding sexual behaviour 2 groups scarce knowledge hpv vaccination found 3 parents mistrust vaccination due lack qualified verified information benefitsconclusionshealthy adolescent sexual behaviour aided communication within family families need information based evidence hpv vaccination health professionals key element process,0.0
effect switching glatiramer acetate formulation 20 mg daily 40 mg three times weekly immune function multiple sclerosis mult scler j exp transl clin 2021 jul 28 7 3 20552173211032323 doi 101177 20552173211032323 ecollection 2021 julsepabstractbackground many rrms patients treated 20 years ga 20 mg ml daily ga20 switched 40 mg ml three timesaweek ga40 reduce injectionrelated adverse events although ga40 effective ga20 reducing annualized relapse rate mri activity remains unknown switching ga40 ga20 affects development pathogenic regulatory immune cellsobjective investigate difference immunological parameters response ga20 ga40 treatmentsmethods analyzed five proinflammatory cytokines il1 il23 il12 il18 tnf three antiinflammatory regulatory cytokines il10 il13 il27 serum addition analyzed six cytokines ifn il17a gmcsf il10 il6 il27 cultured pbmc supernatants development th1 th17 foxp3 tregs m1like m2like macrophages examined flow cytometry samples analyzed 12 months post switching ga40 ga20results pro antiinflammatory cytokines comparable ga40 ga20 groups development th1 th17 m1like macrophages m2like macrophages foxp3 tregs also comparable two groupsconclusions immunological parameters measured rrms patients treated ga40 three times weekly largely comparable given daily ga20 treatmentpmid34377526 pmcpmc8330487 doi101177 20552173211032323,0.0
targeted immune epitope prediction hhla2 mageb5 protein variants therapeutic approach related viral diseases background targeted immunotherapy mostly associated cancer treatment wherein designed molecules engage signaling pathways mutant proteins critical survival cell one several genetic approaches use silico methods develop immune epitopes targeting specific antigenic regions related mutant proteins recent study showed functional association gamma retrovirus hervh long terminal associating hhla1 hhla2 hhla3 proteins melanoma associated antigen b class proteins mageb5 resultant decrease expression hla class ii immune variants hlac hladrb5 main hla class ii immune variants respectively showed expression changes across viral samples interest specific immune variants hlac hladrb5 filtered top ten based relative frequency counts across samplesresultsprotein variants hhla1 hhla2 hhla3 mageb5 used predict antigenic epitope peptides immune peptidemhc class ii binding using artificial neural networks ic50 peptide scores ps 05 transformed binding ability 0 1 top 5 epitopes identified targeted genes hhla1 2 3 mageb5 qualified strong weak binders according threshold domain analysis using ncbi conserved domain database cdd identified hhla2 immunoglobulinlike domains ig_c1set mageb5 mage homology domain mhd linear regression showed statistical correlation p 0001 hhla2 mageb5 predicted epitope peptides hlac hladrb5 prediction model identified hlac variant 9 hlac9 baa088251 hlab1511 11 valuable immune target clinical considerations identification 9mer epitope peptide within domain showed hhla2 yanrtslfy ps 05837 vlayylsssqntiin ps 077 hlac hladrb5 respectively mageb5 peptides fvrltyley ps 05293 ypahyqflwgprayt ps 062 hlac hladrb5 respectivelyconclusionspecific immune responses targeted epitope peptides prediction models suggested coexpression coevolution hhla2 mageb5 viral related diseases hhla2 mageb5 considered markers virus related tumors targeted therapy oncogenic diseases,0.0
several mirnas derived serum extracellular vesicles potential biomarkers early diagnosis progression parkinsons disease background bloodbased test predicting disease progression early diagnosis parkinsons disease pd unmet need clinic profiles micrornas mirnas regarded potential diagnostic biomarkers human diseases whereas mirnas periphery susceptible influence various components mirnas enriched serum extracellular vesicles evs demonstrated diseasespecific advantages diagnosis due high abundance stability resistance degradation study aimed screen differentially expressed evderived mirnas healthy controls pd patients aid diagnosis pdmethodsa total 31 healthy controls 72 patients diagnosis pd different hoehn yahr stages tangdu hospital included total 185 differentially expressed mirnas obtained rna sequencing serum evs well edger ttest analyses subsequently weighted gene coexpression network analysis wgcna utilized identify commonly expressed mirnas stages pd constructing connections modules specifically expressed mirnas stage pd functional enrichment analysis aligning mirnas pdrelated mirnas human mirna disease database screened mirnas validated receiver operating characteristic roc curves quantitative realtime polymerase chain reaction qrtpcr using peripheral blood evs 40 participantsresultswgcna showed 4 mirnas commonly associated stages pd 13 mirnas specifically associated different stages pd 17 obtained mirnas 7 validated roc curve analysis 7 verified 40 participants qrtpcr six mirnas verified methods included 2 mirnas commonly expressed stages pd 4 mirnas specifically expressed different stages pdconclusionsthe 6 serum evderived mirnas hsamir374a5p hsamir374b5p hsamir199a3p hsamir285p hsamir225p hsamir151a5p may potentially used biomarkers pd progression early diagnosis pd populations,0.0
myelin axon pathology multiple sclerosis assessed myelin water multishell diffusion imaging brain 2021 mar 9awab088 doi 101093 brain awab088 online ahead printabstractdamage myelin sheath neuroaxonal unit cardinal feature multiple sclerosis however detailed characterization interaction myelin axon damage vivo remains challenging applied myelin water multishell diffusion imaging quantify relative damage myelin axons among different lesion types ii normalappearing tissue iii across multiple sclerosis clinical subtypes healthy controls also assessed relation focal myelin axon damage disability serum neurofilament light chain global biological measure neuroaxonal damage ninetyone multiple sclerosis patients 62 relapsingremitting 29 progressive 72 healthy controls enrolled study differences myelin water fraction neurite density index substantial lesions compared healthy controls normalappearing ms tissue white matter cortical lesions exhibited decreased myelin water fraction neurite density index compared healthy p 00001 periplaque white matter p 00001 periventricular lesions showed decreased myelin water fraction neurite density index compared lesions juxtacortical region p 00001 p 005 similarly lesions paramagnetic rims showed decreased myelin water fraction neurite density index relative lesions without rim p 00001 also 75 white matter lesions reduction neurite density index higher reduction myelin water fraction besides normalappearing white grey matter revealed diffuse reduction myelin water fraction neurite density index multiple sclerosis compared healthy controls p 001 extensive reduction myelin water fraction neurite density index normalappearing cortex observed progressive versus relapsingremitting participants neurite density index white matter lesions correlated disability patients clinical deficits p 001 beta1000 neurite density index myelin water fraction white matter lesions associated serum neurofilament light chain entire patients cohort p 001 beta360 p 001 beta013 respectively findings suggest myelin axon pathology multiple sclerosis extensive lesions normalappearing tissue ii particular types lesions exhibit damage myelin axons others iii progressive patients differ relapsingremitting extensive axon myelin damage cortex iv myelin axon pathology lesions related disability patients clinical deficits global measures neuroaxonal damagepmid33693571 doi101093 brain awab088,1.0
review nutritional management multiple sclerosis propionate front immunol 2021 jul 28 12676016 doi 103389 fimmu2021676016 ecollection 2021abstractover last 15 years accumulation data supporting concept gutbrain axis whereby dysbiosis gut microbiota can impact neurological function dysbiosis suggested possible environmental exposure triggering multiple sclerosis ms dysbiosis consistently shown result reduction shortchain fatty acid scfa producing bacteria reduction stool plasma levels propionate shown ms patients independent disease stage different geographies wealth evidence supports action propionate tcell activity resulting decreased thelper cell 1 th1 thelper cell 17 th17 numbers activity increased regulatory t cell treg cell numbers activity overall antiinflammatory profile different tcell populations play various roles pathophysiology ms recent clinical study ms patients demonstrated supplementation propionate reduces annual relapse rate slows disease progression review discusses data relevant mechanistic background discusses whether taming overactive immune system ms likely allow easier bacterial viral infectionpmid34394076 pmcpmc8355737 doi103389 fimmu2021676016,0.0
hedgehog pathway suppresses neuropathogenesis cd4 t celldriven inflammation brain 2021 mar 16awab083 doi 101093 brain awab083 online ahead printabstractthe concerted actions cns immune system essential coordinate outcome neuroinflammatory responses yet precise mechanisms involved crosstalk contribution pathophysiology neuroinflammatory diseases largely elude us show cnsendogenous hedgehog pathway signal triggered part host response inflammatory phase multiple sclerosis experimental autoimmune encephalomyelitis attenuates pathogenicity human mouse effector cd4 t cells regulating production inflammatory cytokines using murine genetic model hedgehog signaling compromised cd4 t cells show hedgehog pathway acts cd4 t cells suppress pathogenic hallmarks autoimmune neuroinflammation including demyelination axonal damage thus mitigates development experimental autoimmune encephalomyelitis impairment hedgehog signaling cd4 t cells exacerbates brainbrainstemcerebellum inflammation leads development atypical disease moreover present evidence hedgehog signaling regulates pathogenic profile cd4 t cells limiting production inflammatory cytokines gmcsf ifn antagonizing inflammatory program transcriptome level likewise hedgehog signaling attenuates inflammatory phenotype human cd4 memory t cells therapeutic point view study underlines potential harnessing hedgehog pathway counteract ongoing excessive cns inflammation systemic administration hedgehog agonist disease onset effectively halts disease progression significantly reduces neuroinflammation underlying neuropathology thus unveil previously unrecognized role hedgehog pathway regulating pathogenic inflammation within cns also propose exploit ability modulate neuroimmune network strategy limit progression ongoing neuroinflammationpmid33723591 doi101093 brain awab083,1.0
effectiveness safety simple homebased rehabilitation program pulmonary arterial hypertension interventional pilot study background rehabilitation plays important role management patients pulmonary arterial hypertension pah current guidelines recommend implementation monitored individualized exercise training program adjuvant therapy stable pah patients optimal medical treatment optimal rehabilitation model group patients yet established randomized prospective study assessed effectiveness safety 6month homebased caregiversupervised rehabilitation program among patients pulmonary arterial hypertensionmethodsa total 39 patients pah divided two groups intervention group 16 patients subjected 6month homebased physical training respiratory rehabilitation program adapted clinical status participants control group 23 patients perform physical training 6min walk test 6mwt measurement respiratory muscle strength quality life assessment sf36 fatigue severity scale fss performed study commencement 6 12 months adherence exercise protocol occurrence adverse events also assessedresultsphysical training significantly improved 6mwt distance 7138 834 m 6 months p 0004 remained increased 12 months p 0043 respiratory muscle strength 6 12 months p 001 significant improvement quality life observed training period use sf36 questionnaire physical functioning p 0001 role physical p 0015 vitality p 0022 role emotional p 0029 physical component summary p 0005 persist study completion adherence exercise protocol average 9188 141 serious adverse events notedconclusionaccording study results homebased rehabilitation program dedicated pah patients safe effective improves functional parameters quality life strength respiratory muscles 6mwd remain increased 6 months training cessationtrial registrationclinicaltrialsgov nct03780803 registered 12 december 2018,0.0
surfacein pathology multiple sclerosis new view pathogenesis brain 2021 apr 20awab025 doi 101093 brain awab025 online ahead printabstractwhile multiple sclerosis can affect part cns evenly white matter long recognized lesions tend occur around ventricles grey matter lesions mainly accrue outermost subpial cortex cortical grey matter neuronal loss greater outermost layers cortical gradient replicated vivo magnetization transfer ratio similar gradients grey white matter magnetization transfer ratio seen around ventricles severe abnormalities abutting ventricular surface cause gradients remains uncertain though soluble factors released meningeal inflammation csf supporting evidence update review surfacein spatial distribution multiple sclerosis abnormalities consider implications understanding pathogenic mechanisms treatments designed slow stop thempmid33876200 doi101093 brain awab025,0.0
formation immunomodulatory function meningeal bcell aggregates progressive cns autoimmunity brain 2021 mar 9awab093 doi 101093 brain awab093 online ahead printabstractmeningeal b lymphocyte aggregates described autopsy material patients chronic multiple sclerosis presence meningeal b cell aggregates correlated worse disease however functional role meningeal b cell aggregates understood use mouse model multiple sclerosis spontaneous opticospinal encephalomyelitis model built double transgenic expression myelin oligodendrocyte glycoproteinspecific t cell b cellreceptors show formation meningeal b cell aggregates dependent expression 4 integrins antigenspecific t cells t cellconditional genetic ablation 4 integrins opticospinal encephalomyelitis mice impaired formation meningeal b cell aggregates surprisingly led higher disease incidence compared opticospinal encephalomyelitis mice 4 integrinsufficient t cells b cellconditional ablation 4 integrins opticospinal encephalomyelitis mice resulted entire abrogation formation meningeal b cell aggregates opticospinal encephalomyelitis mice 4 integrindeficient b cells suffered higher disease burden regular opticospinal encephalomyelitis mice anticd20 antibodymediated systemic depletion b cells opticospinal encephalomyelitis mice onset disease failed efficiently decrease meningeal b cell aggregates without significantly modulating disease progression treatment anticd19 chimeric antigen receptort cells eliminated meningeal b cell aggregates exacerbated clinical disease opticospinal encephalomyelitis mice since 20 percent b cells organised meningeal b cell aggregates produced either il10 il35 propose meningeal b cell aggregates might also immunoregulatory function immunopathology adjacent spinal cord white matter immunoregulatory function meningeal b cell aggregates needs considered designing highly efficient therapies directed meningeal b cell aggregates clinical application multiple sclerosispmid33693558 doi101093 brain awab093,1.0
mri brain volume loss lesion burden clinical outcome secondary progressive multiple sclerosis abstractbackgroundmagnetic resonance imaging mri brain volume measures widely used outcomes secondary progressive multiple sclerosis spms unclear whether associated physical cognitive disabilityobjectiveto investigate association mri outcomes physical cognitive disability worsening people spmsmethodswe used data ascend large randomized controlled trial n 889 investigated association change whole brain gray matter volume contrast enhancing lesions t2 lesions significant worsening expanded disability status scale edss timed 25foot walk t25fw ninehole peg test nhpt symbol digit modalities test sdmt logistic regression modelsresultswe found association mri measures edss sdmt worsening t25fw worsening 48 96weeks nhpt worsening 96weeks associated cumulative new newly enlarging t2 lesions 96weeks nhpt worsening 48 96weeks associated normalized brain volume loss 48weeks mri outcomesconclusionthe association standard mri outcomes disability noticeably weak inconsistent 2years followup mri outcomes may useful surrogates disability measures spms,0.0
neuroprotective potential limonene limonene containing natural products molecules 2021 jul 27 26 15 4535 doi 103390 molecules26154535abstractlimonene monoterpene confined family rutaceae showing several biological properties antioxidant antiinflammatory anticancer antinociceptive gastroprotective characteristics recently notable interest investigating pharmacological effects limonene various chronic diseases due mitigating effect oxidative stress inflammation regulating apoptotic cell death several available studies demonstrating neuroprotective role limonene neurodegenerative diseases including alzheimers disease multiple sclerosis epilepsy anxiety stroke high abundance limonene nature safety profile various mechanisms action make monoterpene favorable molecule developed nutraceutical preventive purposes alternative agent adjuvant modern therapeutic drugs curbing onset progression neurodegenerative diseases manuscript presents comprehensive review available scientific literature discussing pharmacological activities limonene plant products containing limonene attribute protective therapeutic ability neurodegenerative disorders review compiled based existing published articles confined limonene limonenecontaining natural products investigated neurotherapeutic neuroprotective potential articles available english abstract english extracted different databases offer access diverse journals databases pubmed scopus google scholar science direct collectively review emphasizes neuroprotective potential limonene neurodegenerative neuroinflammatory diseases available data indicative nutritional use products containing limonene pharmacological actions mechanisms limonene may direct future preclinical clinical studies development limonene alternative complementary phytomedicine pharmacophore can also provide blueprint drug discovery using numerous drug discovery toolspmid34361686 doi103390 molecules26154535,1.0
differential dna methylation early versus late parenteral nutrition picu biological basis impact emotional behavioral problems documented 4years later background pepanic multicenter randomized controlled trial rct shown early administration supplemental parenteral nutrition earlypn compared withholding pn 1 week latepn induced longterm internalizing externalizing total emotional behavioral problems critically ill children observed 4 years later earlypn shown alter methylation status 37 cpgsites leukocyte dna admission discharge pediatric intensive care unit picu preplanned subanalysis pepanic trial now investigated whether altered methylation cpgsites statistically explain negative impact earlypn emotion behavior documented 4 years picu admissionresultsthe combination dna methylation data data behavior 4 years picu admission available 403 1440 patients aged 017 years picu admission included pepanic rct 192 earlypn 211 latepn patients mediation analyses use bootstrapped multivariable nonlinear regression analyses adjusted baseline risk factors revealed adverse alterations earlypn methylation 37 cpgsites together statistically explained harmful impact internalizing externalizing total emotional behavioral problems adding methylation status 37 cpgsites models explanatory power improved 1710 1851fold increase impact altered methylation status cpgsites explained impact randomization earlypn versus latepnconclusionsabnormal dna methylation induced early use pn picu provides biological basis longterm harmful effect emotion behavior critically ill children 4 years picu admissiontrial registration clinicaltrialsgov nct01536275 registered february 17 2012 https clinicaltrialsgov ct2 show nct01536275,0.0
differential disease phenotypes progression relapsingremitting multiple sclerosis comparative analyses single canadian saudi arabian clinics abstractobjectiverelapsingremitting multiple sclerosis rrms phenotypes differ widely although variables contributing heterogeneity remain uncertain assess geographic ethnic effects rrms phenotypes investigated rrms patients canada saudi arabiamethodsa retrospective analysis patients followed two ms clinics performed medina saudi arabia edmonton canada demographic clinical data collected patient analyzed using univariable multivariable statistics univariable multivariable linear regression used distinguish significant clinical demographic features neurological systems associated change expanded disability status scale edss clinical assessmentsresultspatients treated rrms recruited n 51 saudi n 47 canada although disease duration longer canadian cohort 56 22 yr compared saudi cohort 44 14 yr p 005 annual relapse rate edss change higher saudi cohort p 005 infratentorial lesionassociated presentation differed canada n 23 saudi n 13 among groups p 005 spinal cord lesions mri frequently detected canadian n 23 compared saudi n 1 patients p 005 patients within saudi cohort displayed significantly greater change expanded disability status scale edss first second assessmentsconclusionsdespite differences geographic location ethnicity predominance infratentorial lesions canadian group rrms phenotypes similar although saudi cohort displayed severe disease course,0.0
different point view evaluation motor imagery perspectives patients sensorimotor impairments longitudinal study background motor imagery mi successfully applied neurological rehabilitation little known spontaneous selection mi perspectives patients sensorimotor impairments perspective selected internal firstperson view external thirdperson view aim evaluate mi perspective preference patients sensorimotor impairmentsmethodsin longitudinal study including four measurement sessions 55 patients 25 stroke 25 multiple sclerosis 5 parkinsons disease 25 females mean age 58 14 years included mi ability perspective preference visual kinaesthetic imagery modalities assessed using kinaesthetic visual imagery questionnaire20 kviq20 body rotation task brt mental chronometry mc additionally patients activity level assessed descriptive analyses performed regarding different age 45 4564 64 activity levels inactive partially active active kviq20 movement classifications axial proximal distal upper lower limb mixedeffects model used investiage relationship primary outcome mi perspective internal external explanatory variables age mi modality visual kinaesthetic movement type axial proximal distal activity levels different assessments kviq20 brt mc resultsimagery modality significant predictor perspective preference four measurement sessions patients tended become consistent perspective selection however time point significant predictor movement type significant predictor imagination distal vs axial proximal vs axial movements associated preference external perspective patients increased physical activity level tend use internal imagery however effect borderline statistically significant age neither significant precictor regarding mi assessments kviq 20 score significant predictor patients higher test scores tend use external perspectiveconclusionit recommended evaluate spontaneous mi perspective selection design patientspecific mi training interventions distal movements foot finger may indicator evaluating consistency mi perspective patients sensorimotor impairments,0.0
interleukin17 th17 lymphocytes directly impair motoneuron survival wildtype fusals mutant human ipscs int j mol sci 2021 jul 27 22 15 8042 doi 103390 ijms22158042abstractamyotrophic lateral sclerosis als progressive disease leading degeneration motor neurons mns neuroinflammation involved pathogenesis als however interactions specific immune cell types mns well studied recently found shift toward t helper th 1 th17 cellmediated proinflammatory immune responses peripheral immune system als patients positively correlated disease severity progression whether th17 cells central mediator interleukin17 il17 directly affects human motor neuron survival currently unknown evaluated contribution th17 cells il17 mn degeneration using coculture ipscderived mns fused sarcoma fus als patients isogenic controls th17 lymphocytes derived als patients healthy controls multiple sclerosis ms patients positive control th17 cells ms patients induced severe mn degeneration fusals well wildtype mns main effector il17a yielded dosedependent decline viability neurite length mns surprisingly il17f influence mns importantly neutralizing il17a antiil17 receptor treatment reverted effects il17a results offer compelling evidence th17 cells il17a directly contribute mn degenerationpmid34360808 doi103390 ijms22158042,0.0
multiple cardiac fatty deposits patient tuberous sclerosis complex bmj case rep 2021 jul 27 14 7 e244366 doi 101136 bcr2021244366no abstractpmid34315753 doi101136 bcr2021244366,0.0
feasibility specific taskoriented training versus combination manual therapy balance mobility people post stroke chronic stage study protocol pilot randomised controlled trial background large studies shown stroke among relevant causes acquired adult disability walking balance impairment stroke survivors often contribute restriction daily activities social participation taskoriented training tot effective treatment strategy manual therapy mt used successfully enhance ankle joint flexibility population study however compared tot combination mt randomised controlled trial aims pilot study therefore explore feasibility fullscale rct using predefined feasibility criteria secondary aims explore preliminary effects specific tot combined specific totmt versus control group people post strokemethodsthis protocol 4week prospective randomised controlled parallel pilot trial people post stroke chronic stage limited upper ankle joint mobility impairment balance mobility german outpatient therapy centre using 111 allocation 36 patients will randomised one three groups 15min talocrural joint mt plus 30min specific tot group 45min specific tot group b controls group c training will goaloriented including tasks based daily activities increased difficulty utilising predefined progression criteria based patients skill levels interventions will provided facetoface 2 times per week 4 weeks addition 20min concurrent x4 weekly homebased training sessions data will collected blinded assessors baseline postintervention 4week followup primary outcome will feasibility assessed recruitment retention adherence rates compliance adverse events falls acceptability intervention secondary outcomes will walking speed single dual tasking functional mobility ankle range motion disability healthrelated quality lifediscussionfeasibility provided results study will used calculate sample size larger randomised controlled trial investigate effects specific tot specific totmt compared post stroke control grouptrial registrationgerman clinical trials register drks00023068 registered 21092020 https wwwdrksde drks_web navigatedonavigationidtrialhtmltrial_iddrks00023068,0.0
protective mechanism sirt1 cartilage regulation lef1 background osteoarthritis oa chronic degenerative disease suppresses middleaged older people worldwide silent information regulator 1 sirt1 associated several agerelated diseases cardiovascular diseases neurodegenerative diseases tumors etc protective role sirt1 bone joint diseases become increasingly well knownobjectiveto explore relationship sirt1 related factors oamethodsfresh tibial plateau specimens collected 30 patients knee oa underwent total knee arthroplasty according results safranin o fast green staining hematoxylineosin staining oarsi grade developed international association study osteoarthropathy specimens divided mild group moderate group severe group damage cartilage evaluated sirt1 protein levels cartilage samples analyzed immunohistochemistry take 60 8weekold female c57bl 6 j mice apply destabilization medial meniscus dmm induce oa mice randomly divided normal group sham model group model postmodeling drug administration group srt group divided 2 weeks modeling 2 w 8 weeks modeling 8 w according time surgery degenerative degree knee joint mouse knee cartilage samples evaluated using safranin o fast green staining oarsi grade immunohistochemical techniques assessed protein levels sirt1 catenin lef1 mmp13 collagen ii cartilage samples protein levels catenin lef1 mmp13 samples assessed immunohistofluorescence technique mrna expression sirt1 lef1 mouse cartilage samples evaluated realtime quantitative polymerase chain reaction qpcr resultsin human cartilage samples according results safranin o fast green staining compared mild group moderate group severe group showed damage cartilage layer structure number chondrocytes decreased cell hypertrophic cartilage surface discontinuous oarsi grade increased severe group severe cartilage injury highest oarsi grade mice cartilage samples according immunohistochemical analysis protein levels catenin lef1 mmp13 cartilage specimens model 2 w model 8 w groups significantly increased sham 2 w sham 8 w groups protein levels sirt1 collagen ii significantly decreased p 005 results srt 2 w srt 8 w groups sham group model group according immunofluorescence analysis protein levels catenin lef1 mmp13 model 2 w model 8 w groups significantly increased sham 2 w sham 8 w groups results srt 2w srt 8w groups sham group model group according realtime qpcr results compared sham 2 w sham 8 w groups mrna expression sirt1 model 2 w model 8 w groups significantly decreased mrna expression lef1 significantly increased contrast results srt 2 w srt 8 w groups sham group model groupconclusionsrt1720 specific activator sirt1 increase protein level sirt1 sirt1 may play protective role cartilage regulating expression lef1 related inflammatory factors oa,0.0
covid19 severity mortality multiple sclerosis associated immunotherapy insights nationwide austrian registry plos one 2021 jul 27 16 7 e0255316 doi 101371 journalpone0255316 ecollection 2021abstractbackground covid19 pandemic challenges neurologists counselling patients multiple sclerosis pwms regarding risk sarscov2 guiding diseasemodifying treatment dmt objective characterize prevalence outcome covid19 pwms specifically associated different dmt nationwide populationbased studymethods included patients aged 18 years confirmed diagnosis ms diagnosis covid19 established january 1 2020 december 31 2020 classified covid19 course either mild severe fatal impact dmt specifically immunosuppressants alemtuzumab cladribine fingolimod ocrelizumab rituximab covid19 outcome determined multivariable models adjusted aprioririskresults 126 ms patients covid19 mean age 432 years sd 134 71 female 865 mild course 95 severe course 32 died covid19 aprioririsk significantly predicted covid19 severity r2 0814 p0001 mortality r2 0664 p0001 adjusting aprioririsk neither exposure dmt exposure specific immunosuppressive dmt significantly associated covid19 severity odds ratio 16 p 0667 19 p 0426 mortality 05 p 0711 21 0233 compared dmtconclusions populationbased ms cohort covid19 outcome associated exposure dmt immunosuppressive dmt accounting already known risk factors provides reassuring evidence covid19 risk can individually anticipated ms andexcept small proportion highrisk patientstreatment decisions primarily focused treating ms rather pandemicpmid34314457 doi101371 journalpone0255316,0.0
genome pincer wasp gonatopus flavifemur reveals unique venom evolution dual adaptation parasitism predation background hymenoptera comprise extremely diverse insect species extensive variation life histories dryinidae family solitary wasps hymenoptera evolved innovations allow hunt using venom pair chelae developed fore legs can grasp prey dryinidae larvae also parasitoids auchenorrhyncha group including common pests planthoppers leafhoppers traits make effective valuable pest control little yet known genetic basis dual adaptation parasitism predationresultswe sequenced assembled highquality genome dryinid wasp gonatopus flavifemur 6365 mb larger hymenopterans expansion transposable elements especially dna transposons major contributor genome size enlargement genomewide screens reveal number positively selected genes rapidly evolving proteins involved energy production motor activity may contribute predatory adaptation dryinid wasp show three femalebiased reproductiveassociated yellow genes response prey feeding behavior significantly elevated adult females may facilitate egg production venom powerful weapon dryinid wasp parasitism predation therefore analyze transcriptomes venom glands describe specific expansions venom idgflike genes neprilysinlike genes furthermore find lws2opsin gene exclusively expressed male g flavifemur may contribute partner searching matingconclusionsour results provide new insights genome evolution predatory adaptation venom evolution sexbiased genes g flavifemur present genomic resources future indepth comparative analyses hymenopterans may benefit pest control,0.0
ethical use offlabel diseasemodifying therapies multiple sclerosis abstractbackgroundofflabel diseasemodifying therapies dmts multiple sclerosis ms used least 89 countries need structured transparent evidencebased guidelines support clinical decisionmaking pharmaceutical policies reimbursement decisions offlabel dmtsobjectives resultsthe authors put forward general principles ethical use offlabel dmts treating ms process assess existing evidence develop recommendations useconclusionthe principles process endorsed world federation neurology wfn american academy neurology aan european academy neurology ean americas committee treatment research multiple sclerosis actrims european committee treatment research multiple sclerosis ectrims middleeast north africa committee treatment research multiple sclerosis menactrims panasian committee treatment research multiple sclerosis pactrims regularly consulted brain health unit mental health substance use department world health organization,0.0
longterm clinical outcomes hematopoietic stem cell transplantation multiple sclerosis neurology 2021 may 4101212 wnl0000000000011825 doi 101212 wnl0000000000011825 online ahead printno abstractpmid33947786 doi101212 wnl0000000000011825,0.0
effects age disease duration excess mortality patients multiple sclerosis french nationwide cohort neurology 2021 may 19101212 wnl0000000000012224 doi 101212 wnl0000000000012224 online ahead printabstractobjective determine effects current age disease duration excess mortality multiple sclerosis described dynamics excess deaths rates two time scales studied impact age multiple sclerosis clinical onset dynamics separately initial phenotypemethods used data 18 french multiple sclerosis expert centers participating observatoire franais de la sclrose en plaques patients multiple sclerosis living metropolitan france clinical onset 1960 2014 included vital status updated january 1st 2016 multiple sclerosis phenotype separately relapsing onset rms primary progressive ppms used innovative statistical method model logarithm excess death rates multidimensional penalized spline age disease durationresults among 37524 patients 71 women mean age multiple sclerosis onset standard deviation 330 106 years 2883 77 deaths observed 78 patients losttofollowup rms patients excess mortality first 10 years disease onset afterwards whatever age onset excess death rates increased current age current age 70 excess death rates values converged became identical whatever age disease onset means disease duration impact excess death rates higher men excess hazard ratio 146 95 confidence interval 125170 contrast ppms patients excess death rates rapidly increased disease onset associated age onset sexconclusions rms current age stronger impact multiple sclerosis mortality disease duration respective effects clear ppmspmid34011577 doi101212 wnl0000000000012224,0.0
clinical radiologic features pathology treatment balo concentric sclerosis neurology 2021 may 19101212 wnl0000000000012230 doi 101212 wnl0000000000012230 online ahead printabstractobjective describe clinical radiological pathological features patients bals concentric sclerosis bcs assess overlap bcs central nervous system inflammatory demyelinating diseasesmethods retrospective review bcs cases us australian tertiary care centersresults identified 40 bcs cases 38 available mris solitary mri lesions present 26 10 38 saw 1 active concurrent bcs lesion 45 17 38 third 13 38 multiple sclerosissuggestive lesions index mri 10 fulfilled barkhof criteria patients serial mri performed within one month index mri lesions expanded radially sequentially increased numbers t2 hyperintense rings 52 14 27 initially nonenhancing centrally enhancing lesions subsequently developed single multiple enhancing rings 41 9 22 incomplete enhancing rings 14 3 22 discordance rings appear adc dwi gadoliniumenhanced imaging observed 67 22 33 aqp4igg n26 mogigg n21 negative patients serum available clinical response steroid treatment seen 46 13 28 monophasic clinical course present 56 18 32 last followup median 275 months range 3100 months initial attack fatal 10 4 40 median time symptom onset death 23 days range 1949 days 17 patients pathology available demonstrated typical findings multiple sclerosis patients active demyelinating lesions demonstrated oligodendrocytopathy pattern iii conclusions bcs may distinct subtype multiple sclerosis characterized pattern iii immunopathologypmid34011576 doi101212 wnl0000000000012230,1.0
evaluation cholinesterase inhibitory antioxidant activity wedelia chinensis isolation apigenin active compound background wedelia chinensis reported folk medicine treatment different diseases including neurodegenerative disease although plant studied well diverse biological activities effect plant neurological disorder largely unknown present study undertaken evaluate cholinesterase inhibitory antioxidant potential w chinensismethodsthe extract fractions plant evaluated acetylcholinesterase butyrylcholinesterase inhibitory activity modified ellman method antioxidant activity assessed several vitro models assays reducing power total antioxidant capacity total phenolic flavonoid content scavenging 2 2diphenyl1picrylhydrazyl dpph free radical hydroxyl radical inhibition brain lipid peroxidation chromatographic spectroscopic methods used isolate identify active compound extractresultsamong fractions aqueous fraction aqf ethylacetate fraction eaf exhibited high inhibition acetylcholinesterase ic50 4002 016 g ml 5776 037 g ml butyrylcholinesterase ic50 3179 018 g ml 4841 005 g ml similarly eaf aqf high content phenolics flavonoids possess strong antioxidant activity several antioxidant assays including dpph hydroxyl radical scavenging reducing power total antioxidant activity effectively inhibited peroxidation brain lipid vitro ic50 values 4520 010 g ml 2553 004 g ml respectively significant correlation observed total flavonoids antioxidant cholinesterase inhibitory activity activity guided chromatographic separation led isolation major active compound eaf structure elucidated apigenin spectral analysisconclusionsthe potential ability w chinensis inhibit cholinesterase activity peroxidation lipids suggest plant might useful management ad,0.0
willingness receive covid19 vaccine people multiple sclerosis uk ms register survey abstractbackground methods conducted online covid19 survey vaccines became available utilising uk ms register understand people multiple sclerosis pwms views covid19 vaccination subsequent vaccine uptake ratesresults conclusion 944 3191 pwms surveyed indicated get covid19 vaccine 56 pwms previously influenza vaccine increasing age perception sufficient information vaccine associated increased likelihood getting vaccine 517 3191 pwms completed followup survey indicating received least 1 dose covid19 vaccine proportion vaccination based prior opinions 532 yesnull group 270 nonull group latter reflecting change based initial views information covid19 vaccine safety pwms helpful people make informed decisions,0.0
spatiotemporal equalization multiwindow algorithm asynchronous ssvepbased bci j neural eng 2021 jul 8 doi 101088 17412552 ac127f online ahead printabstractobjective asynchronous braincomputer interfaces bcis show significant advantages many practical application scenarios compared rapid development synchronous bcis technology progress asynchronous bci research terms containing multiple targets trainingfree detection still relatively slow order improve practicability braincomputer interface spatiotemporal equalization multiwindow algorithm stemw proposed asynchronous detection steadystate visual evoked potential ssvep without need acquiring calibration dataapproach algorithm used spatiotemporal equalization strategy intercept eeg signals different lengths multiple stacked time windows statistical decisionsmaking based bayesian risk decisionmaking different traditional asynchronous algorithms based noncontrol state detection methods algorithm based statistical inspectionrejection decision mode require separate classification noncontrol states can effectively applied detections largescale candidatesmain results online experimental results involving fourteen healthy subjects showed continuously input experiments 40 targets algorithm achieved average recognition accuracy 97226 average information transfer rate 1063320 bits min time average false alarm rate 240seconds resting state test 06070602 min 1 free spelling experiments involving patients severe amyotrophic lateral sclerosis subjects achieved accuracy 927 average information transfer rate 4365 bits min two free spelling experimentssignificance algorithm can achieve highperformance highprecision asynchronous detection ssvep signals low algorithm complexity false alarm rate multitargets trainingfree conditions helpful development asynchronous bci systemspmid34237711 doi101088 17412552 ac127f,0.0
natalizumab subcutaneous injection treatment relapsing multiple sclerosis patients new delivery route multiple sclerosis ms inflammatory demyelinating neurodegenerative disease central nervous system cns affect around 28 million people worldwide 1 notably ms leading cause nontraumatic neurological disability young adults around world 1,1.0
understanding motivation physical activity charity event participation j health behav 2021 jul 26 45 4 723734 doi 105993 ajhb45411abstractobjectives positive health benefits regular physical activity pa widely known yet pa levels remain low general population neurological conditions like multiple sclerosis ms goal study use lens behavioral economics explore pa motivation participation pabased ms charity fundraising events elucidate relationship behavioral economics constructs motivation methods mixedmethods survey data collected 114 individuals 47 diagnosed ms 67 without ms participated pabased ms charity fundraiser event results quantitative data showed 23 418 participants without ms 16 432 participants living ms cited fundraising ms primary reason participation openended responses revealed behavioral economic constructs framing social support individual positive biases key factors contributing increased motivation participation conclusion habit formation pa behaviors may emerge due personal biases perceived importance fundraising sense relatedness involvement ms charity events may alter social norms frame events enjoyable foster sense community thereby increasing likelihood continued participationpmid34340739 doi105993 ajhb45411,0.0
therapeutic inertia relapsingremitting multiple sclerosis abstractbackgroundtherapeutic inertia ti defined failure initiate intensify treatments despite evidence disease activity prevalence determining factors relapsingremitting multiple sclerosis rrms patients portugal known main objective work ascertain prevalence ti rrms determining factorsmethodswe conducted multicentre retrospective observational study rrms patients followed ms clinics six portuguese hospitals least one medical appointment 2018 ti defined absence treatment initiation intensification therapeutic goals unmet evidence disease activity based definition evidence disease activity neda refers absence clinical relapses absence disease progression measured expanded disability status scale edss absence new disease activity new t2 lesions enhancing lesion magnetic resonance imaging mri period observationresultswe included 427 patients rrms meeting inclusion criteria 696 females mean age 4166 years old mean age diagnosis 3317 years old average number years since diagnosis 872 ms relapses reported 54 patients moderate severe relapses reported 593 median edss score 15 intention get pregnant explicit 39 patients representing 188 women childbearing age among 365 patients mri 238 new t2 lesions 74 enhancing lesions regarding dmt 728 treated interferon glatiramer acetate teriflunomide dimethyl fumarate 206 fingolimod natalizumab rituximab cladribine remaining 66 without treatment adverse events reported 129 patients 101 mentioned preferences regarding treatment ti present 80 187 patients representing 548 potential inertia patients radiologically less active disease already dmt adverse events current treatment likely ti p0 05 also patients followed centers classified higher level care level 1 ti compared patients followed centers levels 2 3conclusionti present 1 5 patients exceeding half sample potential inertia corroborating high prevalence ti studies determining factors ti absence relapses occurrence mild relapses already dmt absence adverse events followup higher care level centers ti topic rarely addressed ms work highlights importance therapeutic optimization patients studies held explore factors influence ti great impact therapeutic decisions,1.0
regulatory macrophages tolerogenic dendritic cells myeloid regulatory cellbased therapies int j mol sci 2021 jul 26 22 15 7970 doi 103390 ijms22157970abstractmyeloid regulatory cellbased therapy shown promising cellbased medicinal approach organ transplantation treatment autoimmune diseases type 1 diabetes rheumatoid arthritis crohns disease multiple sclerosis dendritic cells dcs efficient antigenpresenting cells can naturally acquire tolerogenic properties variety differentiation signals stimuli several subtypes dcs generated using additional agents including vitamin d3 rapamycin dexamethasone immunosuppressive cytokines interleukin10 il10 transforming growth factorbeta tgf cells extensively studied animals humans develop clinicalgrade tolerogenic tol dcs regulatory macrophages mregs another type protective myeloid cell provide tolerogenic environment mainly studied within context research organ transplantation review aims thoroughly describe ex vivo generation toldcs mregs mechanism action well therapeutic application assessment human clinical trialspmid34360736 doi103390 ijms22157970,0.0
gait speed trajectory sixminute walk test multiple sclerosis measure walking endurance front neurol 2021 jul 26 12698599 doi 103389 fneur2021698599 ecollection 2021abstractbackground sixminute walk 6mw test validated assessment method multiple sclerosis ms research total distance covered six minutes 6mwtd often used standard measurement gait capacity ie maximum distance one can achieve hypothesize endurance ie ability maintain speed prolonged time can inferred gait speed trajectory gst 6mw test 6mwgst objective characterize group differences 6mwgst ms patients healthy controls hcs assess information added 6mwgst discerning ms patients hcs methods performed secondary data analysis crosssectional cohort 40 ms 20 hc subjects three repeated 6mw tests modeled 6mwgst using linear mixedeffects model time minutes replicated walks nested within individuals compared discernibility 6mwgst conventional metrics using likelihood ratio tests receiver operating characteristic roc analysis logistic regression models results ms subjects showed concave quadratic gst 6mw tests slowing hc subjects especially beginning 6mw tests despite accelerating end 6mw ms subjects unable attain surpass initial 6mw gait speeds 6mwgst added useful information p 0002 conventional metrics eg 6mwtd discerning ms hc subjects increased area roc curve 083 093 p 0037 conclusions distinctive 6mwgst pattern ms patients provided increased discernibility compared currently used gait metrics gait capacity measured 6mwtd gait endurance measured parameters 6mwgst significant functional indicators ms populationpmid34381416 pmcpmc8352578 doi103389 fneur2021698599,0.0
investigation common risk factors polycystic ovary syndrome alzheimers disease narrative review background common endocrine metabolic disorders premenopausal women polycystic ovary syndrome pcos characterized hyperandrogenism chronic anovulation ultrasound evidence small ovarian cysts obesity insulin resistance also main factors influencing clinical manifestations syndrome alzheimers disease ad typical progressive neurodegenerative disorder brain recent studies suggest relationship endocrinal dysregulation neuronal loss ad pathologyaimthis study aimed evaluate common risk factors alzheimers pcos based previous studies knowing common risk factors eliminating may prevent neurodegenerative alzheimers disease futuremethodin narrative review international databases including google scholar scopus pubmed web science searched retrieve relevant studies relevant studies summaries categorized discuss possible pathways may explain association alzheimers pcos signs symptoms complicationsresultsaccording research factors involved alzheimers pcos disorders may share common risk factors patients pcos increased lh fsh ratio decreased vitamin d insulin resistance obesity important factors may increase risk alzheimers disease,0.0
highparameter cytometry unmasks microglial cell spatiotemporal response kinetics severe neuroinflammatory disease background differentiating infiltrating myeloid cells resident microglia neuroinflammatory disease challenging bone marrowderived inflammatory monocytes infiltrating inflamed brain adopt microglialike phenotype precludes accurate identification either cell type without genetic manipulation important understand temporal contribution disease inform effective intervention pathogenesis west nile virus wnv encephalitis widespread neuronal infection drives substantial cns infiltration inflammatory monocytes causing severe immunopathology death role microglia remains unclearmethodsusing highparameter cytometry dimensionalityreduction devised simple novel gating strategy identify microglia infiltrating myeloid cells wnvinfection validating strategy 1 blocked entry infiltrating myeloid populations peripheral blood using monoclonal blocking antibodies 2 adoptively transferred bmderived monocytes tracked phenotypic changes infiltration 3 labelled peripheral leukocytes infiltrate brain intravenous dye demonstrated myeloid immigrants populated identified macrophage gates plx5622 depletion reduced 4 subsets defined microglial gatesresultsusing gating approach identified four consistent microglia subsets homeostatic wnvinfected brain p2ry12hi cd86 p2ry12hi cd86+ p2ry12lo cd86 p2ry12lo cd86+ infection 2 populations identified inflammatory microglialike macrophages recruited bone marrow detailed kinetic analysis showed significant increases proportions p2ry12lo microglia subsets anatomical areas largely expense p2ry12hi cd86 subset latter undergoing compensatory proliferation suggesting replenishment differentiation subset response infection microglia altered morphology early infection cells adopting temporal regional diseasespecific phenotypes late disease microglia produced il12 downregulated cx3cr1 f4 80 tmem119 underwent apoptosis infiltrating macrophages expressed tmem119 p2ry12 de novo microglialike subset notably exhibiting highest proportional myeloid population deathconclusionsour approach enables detailed kinetic analysis resident vs infiltrating myeloid cells wide range neuroinflammatory models without nonphysiological manipulation will clearly inform potential therapeutic approaches specifically modulate cells,0.0
french recommendations management systemic sclerosis abstractsystemic sclerosis ssc generalized disease connective tissue arterioles microvessels characterized appearance fibrosis vascular obliteration two main phenotypical forms ssc diffuse cutaneous form extends towards proximal region limbs torso limited cutaneous form cutaneous sclerosis affects extremities limbs without passing beyond elbows knees also exists less 10 cases forms never involve skin called ssc sine scleroderma prognosis depends essentially occurrence visceral damage particularly interstitial lung disease sometimes severe pulmonary arterial hypertension primary cardiac damage represent three commonest causes mortality ssc another type involvement poor prognosis scleroderma renal crisis rare less 5 cases cutaneous extension also important parameter diffuse cutaneous forms less favorable prognosis,0.0
results spectrum survey healthcare professionals understand current diagnosis management practices secondary progressive multiple sclerosis united kingdom abstractbackgroundrecognising transition relapsing remitting multiple sclerosis rrms secondary progressive ms spms clinical practice can challenging diseasemodifying therapies dmts commonly used rrms accepted less efficacious progression occurred treatment options progressive forms ms limited emergence new dmts spms changing treatment landscape need better understand current practice factors underlying facilitate consensus overall management spms optimise diagnostic management decisions survey project aimed assess current practices diagnosis management patients spms ukmethods healthcare professionals hcps involved management patients spms geographically distributed ms neurology centres uk participated facetoface telephone interviews facilitated semistructured questionnaire survey data descriptively analysed using quantitative qualitative methodsresults fiftynine hcps 41 neurologists 15 specialist nurses 3 othernull 59 uk centres took part sixtyone percent n36 59 respondents applied specific definition spms although 6 2 36 used lublin 2014 phenotype criteria expanded disability status scale edss score increase absence relapses important consideration spms diagnosis 83 n49 59 respondents 36 n21 59 considered important piece evidence look suspect patient transitioning rrms spms median interquartile range iqr estimated time first suspicion diagnosis spms 12 months 1224 n45 59 concerns withdrawing dmts psychological impact diagnosis patients commonly reported reasons reluctance diagnose seventythree percent n43 59 respondents followed specific guidelines dmt management patients transitioning rrms spms 86 n37 43 using nhs england algorithm ninetyeight percent n58 59 use dmts treat patients suspect may transitioning spms 51 n30 59 reported using dmts newly diagnosed spms patients approximately 1 5 hcps may consider continuing dmts beyond edss 70 certain circumstancesconclusion survey highlighted variation across uk spms definition diagnosis reported realworld management disparity practice may result unnecessary variations treatment patterns consequently outcomes hcps equipped make timely accurate decisions will important improving access appropriate therapies patients spms,0.0
decreased neurofilament l chain levels cerebrospinal fluid tolerogenic plasmacytoid dendritic cells natalizumabtreated multiple sclerosis patients brief research report front cell neurosci 2021 jul 26 15705618 doi 103389 fncel2021705618 ecollection 2021abstractbackground neurofilament light nfl chain levels cerebrospinal fluid csf serum correlated reduction axonal damage multiple sclerosis ms patients treated natalizumab ntz however little known function plasmacytoid cells ntztreated ms patientsobjective evaluate csf nfl serum levels solublehlag shlag eventual tolerogenic behavior plasmacytoid dendritic cells pdcs ms patients ntz treatmentmethods csf nfl serum shlag levels measured using elisa assay pdcs bdca2+ accessed flow cytometry analysesresults csf levels nfl significantly reduced ntz treatment serum levels shlag increased moreover ntz treatment enhanced tolerogenic hlag+ cd274+ hladr+ molecules migratory ccr7+ functions pdcs peripheral bloodconclusion findings suggest ntz stimulates production molecules immunoregulatory function hlag cd274 programmed deathligand 1 pdl1 may contribute reduction axonal damage represented decrease nfl levels patients mspmid34381335 pmcpmc8350727 doi103389 fncel2021705618,0.0
tremor dysmetria multiple sclerosis neurophysiological study tremor hyperkinet mov n y 2021 jul 26 1130 doi 105334 tohm598 ecollection 2021abstractobjective mechanisms contributing pathogenesis tremor dysmetria multiple sclerosis ms poorly understood abnormal oscillations within olivocerebellothalamocortical networks believed play important part tremor aetiology also contribute intention dysmetria due disruptions motor timing conversely delayed central motor conduction times common feature ataxias also contribute expression dysmetria ms study examined roles central conduction delays manifestation tremor dysmetria msmethods twentythree individuals ms participated 8 movement disorder 6 tremor 4 pure dysmetria 5 tremor dysmetria median nerve somatosensory evoked potentials seps transcranial magnetic stimulation tms motor cortex cervical spine stretch reflexes used assess sensory motor conduction timesresults central peripheral sensory conductions time significantly delayed participants dysmetria regardless presence tremor similarly tms evoked muscles responses longlatency component stretch reflexes significantly delayed dysmetria pure tremorconclusion dysmetria ms associated delays central conduction sensory motor pathways likely leading disruption muscle activation timing terminal oscillations contribute dysmetriasignificance presence dysmetria ms associated decreased conduction velocities central sensory motor pathways likely reflects greater demyelination axons compared movement disorder pure tremorpmid34395055 pmcpmc8323523 doi105334 tohm598,1.0
pathogenesis autoimmune demyelination multiple sclerosis neuromyelitis optica spectrum disorders myelin oligodendrocyte glycoprotein antibodyassociated disease clin transl immunology 2021 jul 26 10 7 e1316 doi 101002 cti21316 ecollection 2021abstractautoimmunity plays significant role pathogenesis demyelination multiple sclerosis ms neuromyelitis optica spectrum disorders nmosd myelin oligodendrocyte glycoprotein antibodyassociated disease mogad now recognised separate disease entities amalgam human central nervous system demyelinating disorders disorders share inherent similarities investigations distinct clinical presentations lesion pathologies aided differential diagnoses understanding disease pathogenesis interplay various genetic environmental factors contributes disease many implicate autoimmune response pivotal role adaptive immune system highlighted diagnostic autoantibodies nmosd mogad presence autoreactive lymphocytes ms lesions number autoantigens proposed ms recent emphasis contribution b cells shed new light wellestablished understanding t cell involvement pathogenesis review aims synthesise clinical characteristics pathological findings discuss existing emerging hypotheses regarding aetiology demyelination evaluate recent pathogenicity studies involving t cells b cells autoantibodies implications human demyelinationpmid34336206 pmcpmc8312887 doi101002 cti21316,1.0
new diagnostic sampling method pure neural leprosy scraping myelin sheath dear editor pure neural leprosy pnl form leprosy characterized neural involvement without skin lesions1 pnl affects 310 patients leprosy can occur spectrum although frequent tuberculoid type2 present case patient affected pnl diagnosed scraping myelin sheaths ulnar nerve ziehlneelsen zn staining polymerase chain reaction pcr 78yearold man professional missioner philippines papua new guinea presented sensory loss touch pain temperature left foot pain left hand present period 4 years physical examination revealed dorsal flexion deficit left foot superficial paraesthesia dysesthesia toes associated impaired deep sensitivity addition presented paraesthesia dysesthesia iv v fingers left hand left ulnar nerve palpable enlarged left elbow cutaneous lesions found research acidfast bacillus afbs nasal swab slit skin smears earlobes left elbow negative motor sensory action potential left ulnar nerve left peroneal nerve left anterior posterior tibial nerves suggestive mononeuritis multiplex magnetic resonance imaging mri left elbow showed enlarged ulnar nerve partially damaged entrapment within fibroosseous tunnel neurosurgery allowed debridement ulnar nerve time scraping perineural tissue zn stain pcr scraping positive presence m leprae diagnosis tuberculoid leprae pnl made antibodies phenolic glycolipid1 antigen antipgl antibody negative therapy based combination three drugs rifampicin 600 mg month dapsone 100 mg daily clofazimine 300 mg month 50 mg daily associated prednisone 25 mg gabapentin 300 mg 2 cp die started improvement symptomsto best knowledge first case pnl diagnosed scraping zn staining pcr test scraping technique allows obtaining clinical specimen rubbing part body case myelin sheaths nerve surface scraped 15 bardpaker blade held right angle incision upon scraping perineural tissue obtained examined zn staining pcr test traditionally diagnostic criteria diagnosis pnl consist nerve tissue samples obtained nerve biopsy analysis pcr measure antipgl1 antibody levels3 however invasive procedure nerve biopsy criticized abhishek de et al high rate complications4 proposed simple technique fnac coupled pcr pilot study4 confirmed efficacy 4year study5 case use technique fnac invasive procedure surgery required solve compression ulnar nerve cubital tunnel however scraping myelin sheath simple tissue sampling method surgical procedures less risk nerve damage,1.0
multiyear systematic survey quality reporting randomised trials dentistry neurology geriatrics published journals spain latin america background iberoamerican cochrane network currently developing extensive project identify spanishlanguage journals publish original clinical research spain latin america project called baderi database iberoamerican essays journal feeds research articles mainly randomised clinical trials rcts central cochrane collaboration central register controlled trials study aims assess quality reporting rcts published spanish latin american journals three clinical fields assess changes timemethodswe systematic survey time trend analysis rcts dentistry geriatrics neurology fields chosen pragmatic reasons yet completed baderi screening rcts 1990 2018 randomised quasirandomised clinical trials extracted data 23 consort items primary outcome total score 23 predefined consort 2010 items rct score range 0 34 secondary outcome measure score one 23 itemsresultsa total 392 articles 1990 2018 included follows dentistry 282 neurology 80 geriatrics 30 found overall compliance score consort items included study 392 rcts analysed 126 scale maximum score 34 time quality reporting improved slightly rcts none articles achieved complete individual consort item compliance score lowest overall compliance percentage item 10 randomisation implementation item 24 protocol registration dismal 1 compliance across included rcts regardless countryconclusionsconsort compliance poor 392 analysed rcts impact consort statement improving completeness rct reporting latin america spain clear iberoamerican journals become involved endorsing enforcing adherence consort guidelines,0.0
homebased exercise training multiple sclerosis systematic review implications future research abstractbackgroundsubstantial evidence supports benefits supervised exercise training et people multiple sclerosis ms however limitations transportation problems preventing physical activity people ms one opportunity increasing physical activity participant people ms homebased exercise training hbet yet unaware systematic review hbet people ms undertook systematic review enhancing knowledge hbet people msmethodsto identify eligible studies included medical subject headings mesh keywords including multiple sclerosisnull msnull degenerative nerve diseasenull homebased exercisenull homebased trainingnull homebased balance trainingnull homebased rehabilitationnull physical telerehabilitationnull homebased walkingnull homebased step trainingnull studies included review examined effect hbet people ms written english available fulltextresultsaccording inclusion exclusion criteria 24 studies judged eligible included systematic review results indicated total number 10 studies mainly implemented combined et interventions balance aerobic et included 5 studies three studies administered resistance et interventions one study applied exergaming moreover 13 studies focused effects et physical fitness one article reflected impact et fatigue nine cases included fatigue quality life fitness outcome measuresconclusionshomebased et 27 times per week beneficial feasible safe people ms nevertheless notable limitations including adherence interventions needs addressed future studies b disabilityrelated outcomes considered future hbet studies,0.0
pd1 pdl1 axis potential therapeutic target multiple sclerosis t cell perspective front cell neurosci 2021 jul 26 15716747 doi 103389 fncel2021716747 ecollection 2021abstractthe programmed cell death protein1 programmed death ligand1 pd1 pdl1 axis widely studied immune checkpoint modulates signaling pathways related t cell activation use pd1 pdl1 inhibitors promising immune therapy strategy cancer patients however individuals treated pd1 pdl1 inhibitors may develop immunerelated adverse events due excessive immune reactions multiple sclerosis ms chronic demyelinating neurodegenerative disease central nervous system t cells pd1 pdl1 axis play vital roles pathogenesis ms better understanding complex relationship pd1 pdl1 axis t cells may extend knowledge molecular mechanisms therapeutic approaches ms review summarize recent findings regarding role pd1 pdl1 axis ms discuss potential therapeutic strategies modulate expression pd1 pdl1 mspmid34381337 pmcpmc8350166 doi103389 fncel2021716747,1.0
mitochondrial mutations multiple sclerosis patients atypical optic neuropathy abstractbackground multiple sclerosisrelated optic neuritis mostly associated good recovery aim study investigate causes progressive visual worsening multiple sclerosis patients despite treatmentmethods retrospectively reviewed medical records multiple sclerosis patients optic neuritis admitted ward neurology department 2001 2020 patients unilateral bilateral progressive visual loss nonsubstantial recovery visual acuity screened genetic testing lebernulls hereditary optic neuropathyresults 1014 multiple sclerosis patients 411 39 reported optic neuritis followup 11 patients manifested atypical characteristics multiple sclerosisrelated optic neuritis presence one following clinical findings bilateral simultaneous sequential eye involvement progressive visual loss response corticosteroids hospitalization others presented typical multiple sclerosisrelated optic neuritis multiple sclerosis patients atypical characteristics optic neuritis screened possible etiologies optic neuropathy found pathogenic mitochondrial mutations 5 patients multiple sclerosis study groupconclusion study group prevalence mitochondrial mutations among multiple sclerosis patients optic neuritis 012 strongly recommend investigating lebernulls hereditary optic neuropathy mutations ms patients suffer severe bilateral visual loss without recovery followup lebernulls hereditary optic neuropathy mitochondrial mutations indicate relatively poor visual prognosis important implications genetic counseling,0.0
cysteinecontaining cellpenetrating peptide ap enables efficient macromolecule delivery t cells controls autoimmune encephalomyelitis pharmaceutics 2021 jul 25 13 8 1134 doi 103390 pharmaceutics13081134abstractt cells key immune cells involved pathogenesis several diseases rendering important therapeutic targets although drug delivery t cells subject continuous research remains challenging deliver drugs primary t cells used peptidebased drug delivery system ap previously developed transdermal delivery peptide modulate t cell function first identified apconjugated enhanced green fluorescent protein egfp efficiently delivered nonphagocytic human t cells also confirmed nineamino acid sequence one cysteine residue optimal sequence protein delivery t cells next identified biodistribution apdtomato protein vivo systemic administration transduced various tissues spleen liver intestines even brain across bloodbrain barrier next confirm apbased t cell regulation synthesized apconjugated cytoplasmic domain ctla4 apctctla4 peptide apctctla4 reduced il17a expression th17 differentiation conditions vitro ameliorated experimental autoimmune encephalomyelitis decreased numbers pathogenic il17a+gmcsf+ cd4 t cells results collectively suggest ap peptide can used successful intracellular regulation t cell function especially cnspmid34452095 doi103390 pharmaceutics13081134,0.0
crosssectional survey cannabis use people ms oregon southwest washington abstractbackground evidence supports cannabinoids reduce selfreported spasticity neuropathic pain people ms pwms legal access cannabis medical recreational use continues rise however limited data regarding patterns cannabis use perceived benefits cannabis among pwms us study describes prevalence cannabis use routes administration perceived benefit cannabis ms characteristics associated cannabis use perception benefit among population pwms living two states cannabis legal medical recreational usemethods survey treatments used pwms focusing complementary alternative medicine cam sent pwms living oregon southwest washington survey included questions current past cannabis use route cannabis administration perceived benefits well personal demographicsresults 1188 returned surveys 1000 least 75 complete survey responses also completed questions current past cannabis use thirty percent n303 respondents reported currently using cannabis 21 n210 used past currently 49 n487 never used cannabis among current users rates use smoking vaping topicals tinctures oils edibles similar 3546 59 reported using multiple routes administration 6478 varying route current past users reported cannabis somewhat beneficial msthe odds current cannabis use higher pwms 1 younger 224 95 ci 139361 age 1840 compared age 60 2 lower household income 394 95 ci 255609 annual income 25k compared 100k 3 secondary progressive ms 177 95 ci 107292 4 minimal ms disability 205 95 ci 103410 using walker compared none minimal disability odds perceiving cannabis beneficial ms higher 1 younger individuals 561 95 ci 2621198 age 1840 compared age 60 2 lower household income 335 95 ci 165680 annual income 25k compared 100k 3 currently using disease modifying therapies 232 95 ci 130413 4 greatest disability 1796 95 ci 20016122 conclusion survey 30 pwms reported currently using cannabis ms mostly multiple routes administration people report helpful ms people younger lower household income progressive disease minimal disability likely use cannabis report beneficial ms people using disease modifying therapies also likely report benefit cannabis use,0.0
astrocytic yap protects optic nerve retina experimental autoimmune encephalomyelitis model tgf signaling theranostics 2021 jul 25 11 17 84808499 doi 107150 thno60031 ecollection 2021abstractrationale optic neuritis one main symptoms multiple sclerosis ms causes visual disability astrocytes pivotal regulators neuroinflammation ms astrocytic yesassociated protein yap plays critical role neuroinflammation meanwhile yap signaling involved visual impairment including glaucoma retinal choroidal atrophy retinal detachment however roles underlying mechanisms astrocytic yap neuroinflammation demyelination msrelated optic neuritis mson remains unclear methods assess functions yap mson experimental autoimmune encephalomyelitis eae common model ms established mice conditional knockout cko yap astrocytes yapgfapcko mice successfully generated behavior tests immunostaining nissl staining hematoxylineosin staining tunel staining luxol fast blue lfb staining electron microscopy em quantitative realtime pcr qpcr gene set enrichment analysis gsea gene set variation analysis gsva rna sequencing used examine function mechanism yap signaling based yapgfapcko mice eae model mice explore potential treatment yap signaling eae eae mice treated various drugs including sri011381 agonist transforming growth factor tgf pathway xmump1 inhibits hippo kinase mst1 2 activate yap results found yap significantly upregulated activated astrocytes optic nerve eae mice conditional knockout yap astrocytes caused severe inflammatory infiltration demyelination optic nerve damage retinal ganglion cells rgcs eae mice moreover yap deletion astrocytes promoted activation astrocytes microglia inhibited proliferation astrocytes optic nerve eae mice mechanically tgf signaling pathway significantly downregulated yap deletion astrocytes additionally qpcr immunofluorescence assays confirmed reduction tgf signaling pathway yapgfapcko eae mice interestingly sri011381 partially rescued deficits optic nerve retina yapgfapcko eae mice finally activation yap signaling xmump1 relieved neuroinflammation demyelination optic nerve eae mice conclusions results suggest astrocytic yap may prevent neuroinflammatory infiltration demyelination upregulation tgf signaling provide targets development therapeutic strategies tailored msonpmid34373754 pmcpmc8344002 doi107150 thno60031,1.0
clinical study new risk assessment prediction system early osteonecrosis femoral head zhongguo gu shang 2021 jul 25 34 7 61722 doi 1012200 jissn10030034202107006abstractobjective establish risk assessment prediction system early osteonecrosis femoral head onfh order predict collapse riskmethods risk assessment system early necrosis collapse femoral head established based combination steinberg stage abc typing proportion proximal sclerotic rim firstly steinberg stage system applied abc typing applied predict risk stage type c risk free type b low risk type type bc medium risk type ac type ab high risk classification proximal sclerotic rim first applied steinberg stage type 2 expected low risk classification proximal sclerotic rimwas type 1 abc typing applied type c riskfree type b low risk type type bc medium risk type ac type ab high risk according prediction system collapse risk femoral head 188 cases 301 hips predicted retrospective analysis hips enrolled outpatient department orthopedic guanganmen hospital attached china academy chinese medical science consistency prediction results three doctors one doctor different times evaluatedresults among 136 cases male 52 female 75 cases single hip 113 double hip age patients wa 19 64 42611207 years natural course disease 033 500 362193 years 206 hips 301 hips collapsed collapse rate 6844 riskfree group none hip collapsed collapse rate 0 lowrisk group 9 hip 91 hips collapsed collapse rate 989 mediumrisk group 12 hip 19 hips collapsed collapse rate 6316 high risk group 185 hips 190 hips collapsed collapse rate 9737 significantly differences collapse rate p000 following orderhighrisk group mediumrisk lowrisk group riskfree group prediction value system high auc095 p000 results predicted different doctors consistent icc094 p000 results predicted doctor two different times consistent kappa coefficient 090 p000 conclusion risk assessment prediction system early onfh selects different methods predict risk collapse according imaging characteristics different stages combines comprehensive assessment multiple risk factors system applicable wide range simple operation convenient clinical applicationpmid34318636 doi1012200 jissn10030034202107006,0.0
coronavirus disease 2019 latin american patients multiple sclerosis abstractpatients multiple sclerosis ms present coronavirus disease 2019 covid19 particular interest neurologists patients neuroimmune disease receive immunomodulatory immunosuppressive therapies longterm present data 73 patients ms confirmed diagnosis covid19 five latin american countries fifteen patients 205 hospitalized two patients died use anticd20 therapies risk factor associated hospitalization death despite small sample size study highlights awareness regarding therapeutic options ms pandemic,0.0
therapeutic plasma exchange ms refractory relapses longterm outcome abstractintroductiontherapeutic plasma exchange tpe considered treatment option steroidrefractory multiple sclerosis ms relapses objective assess longterm clinical response tpe ms steroidrefractory exacerbationsmethodsretrospective study relapsing remitting ms rrms patients presenting intravenous methylprednisolone ivmps refractory relapses underwent tpe response tpe assessed 1 3 6 12 24months posttreatment compared second group rrms patients similar demographic clinical characteristics presenting ivmpsrefractory relapses treated tpe multivariate regression analysis used assess potential predictors significant clinical responseresultsbetween 2011 2020 total 23 rrms patients treated tpe twentyone patients receiving treatment served controls differences demographic clinical characteristics predictors clinical improvement tpe detected groups seventyeight percent patients treated tpe presented clinical improvement 24 months tpetreated patients presented lower edss scores 6 24 months younger age presence gadoliniumenhancing lesions tpe treatment associated better clinical outcomes lifethreatening side effects reportedconclusionstpe safe well tolerated procedure decreases longterm disability rrms patients ivmpsrefractory relapses,1.0
enhancement balance mobility individuals multiple sclerosis using visual cue guided multidirectional step training pilot study abstractbackgroundindividuals multiple sclerosis ms often experience limitations mobility due impairment gait balance rehabilitation approaches improve balance mobility individuals ms limited developed novel visual cue guided multidirection step mds training method improve balance mobility individuals msobjectiveto examine effect mds training balance gait mobility individuals msmethodsfive individuals relapsing remitting ms participated 4week training involving stepping eight directions response visual cue balance gait mobility assessed trainingresultstraining related improvements seen limits stability p 05 spatial temporal gait parameters p05 performance tinetti mobility assessment p001 10meter walk test p001 foursquare step test p002 conclusionbalance gait mobility individuals ms improved 4 weeks visual cue guided multidirection stepping training outcomes feasibility study help refocus conventional rehabilitation strategies aimed aiding individuals ms achieve maximal independence mobility,1.0
thalamus trigeminal neuralgia structural metabolic abnormalities influence surgical response background medicallyrefractory trigeminal neuralgia tn can treated successfully operative intervention significant proportion patients nonresponders despite undergoing technically successful surgery thalamus key component trigeminal sensory pathway involved transmitting facial pain role thalamus tn influence durability pain relief tn surgery relatively understudied aimed test hypothesis variations thalamic structure metabolism related surgical nonresponse tnmethodswe performed longitudinal perioperative neuroimaging study thalamus medicallyrefractory tn patients undergoing microvascular decompression percutaneous balloon compression rhizotomy patients underwent structural mri mr spectroscopy scans preoperatively 1week following surgery classified responders nonresponders based 1year postoperative pain outcome thalamus volume shape metabolite concentration choline creatine cho cr nacetylaspartate creatine naa cr evaluated baseline 1week compared responders nonresponders healthy controlsresultstwenty healthy controls 23 patients medicallyrefractory tn treated surgically 17 responders 6 nonresponders included preoperatively tn patients group showed significantly larger thalamus volume contralateral side facial pain however vertexwise shape analysis showed significant contralateral thalamus volume reduction nonresponders compared responders axiallyoriented band spanning outer thalamic circumference peak p 0019 preoperative thalamic metabolite concentrations differ responders nonresponders early 1week surgery longterm nonresponders showed distinct decrease contralateral thalamic cho cr naa cr irrespective surgery type observed respondersconclusionsatrophy contralateral thalamus consistent feature across patients medicallyrefractory tn regional alterations preoperative thalamic structure early postoperative metabolic changes thalamus appear influence durability pain relief tn surgery,0.0
evaluation ocrelizumab older progressive multiple sclerosis patients abstractbackgroundseminal trials evaluating anticd20 therapy progressive ms primarily found benefit younger lessdisabled patients inflammatory disease activity risks benefits ocrelizumab use older patients progressive froms ms knownmethodsretrospective chart review performed patients older 55 primary secondary progressive ms time ocrelizumab initiation clinical endpoints 2 years prior anticd20 therapy served withinsubject controlresultsdata reviewed 56 patients older age 55 time ocrelizumab initiation 37 patients 2years follow ocrelizumab 40 n15 experienced confirmed disability progression cdp 60 n22 remained stable improved 24 patients data available withinsubject control patients median age 67 baseline edss 63 disease duration 205 years prior anticd20 therapy 58 n14 patients remained stable 42 n10 experienced cdp ocrelizumab initiation 71 n17 remained stable 29 n7 experienced cdp difference cdp p054 change edss p009 time periods ocrelizumab well tolerated difference infection rate seen using withinsubject controlconclusionswe found difference clinical endpoints patients ocrelizumab compared prior anticd20 therapy however exclude modest effect given sample size larger trials needed evaluate ocrelizumab use understudied ms subpopulation,0.0
optimizing telemedical care neurological outpatients characterizing patients needs physicianpatient relationshipcontent analysis guidelinebased interviews background use new concepts patient care videoconsultations reminder systems online evaluation portals becoming increasingly important physicianpatient relationship outpatient care study examines acceptance approaches neurological setting determines patients preferencesmethodswe analyzed 16 guidelinebased qualitative interviews neurological patients using qualitative content analysis inductive category formation resultsthe patients commented benefits challenges integrating new concepts medical care identified advantages telemedical care including time savings 7 16 43 8 patient physician prospect intensive 4 16 25 care possibility quick response case urgent needs 3 16 188 several challenges reported limitations patients psychiatric 2 16 125 complex diseases 4 16 25 limited options diagnostic procedures physical examination 4 16 25 individual neurological patients needs telemedical telecommunication structures discussed support patients specific requirements answering questions recall 2 16 125 avoiding journey 8 16 50 also patients rejecting evaluation portals skeptical telecare treatment neurological diseasesdiscussionthe perception telemedical care successful integration new medical care concepts depend fulfilling individual patients needs regardless preferred nature physicianpatient interactions specific instruments can intensify relationship individual needs patients must inquired accommodated forconclusionsfor first time characterize properties optimal telemedical care neurological patients interviews like ones conducted repeated pandemic referring results compare,0.0
brain atrophy rates patients multiple sclerosis long term natalizumab resembles healthy controls abstractbackgroundclinically stable multiple sclerosis ms patients often negligible inflammatory mri changes brain atrophy may provide insight subclinical disease progression objective compare brain atrophy rates stable patients long term natalizumab treatment vs age gender matched healthy nonms controls hc prospectively twoyears examining brain volume cognition patient reported outcomes pros methodsms patients treated natalizumab minimum 2 years age 1860 recruited compared age gendermatched healthy controls hc groups followed prospectively obtain two years consecutive magnetic resonance imaging clinical pro data baseline normalized brain volume nbv yearly t2 lesion volume t2lv percent brain volume change pbvc measured using sienax jim 60 siena respectively neuropsychological tests macfims battery selected optimize assessments impairments domains information processing speed memory patient reported outcomes pros domains physical mental social quality life evaluated using neuroqol short formsresultsfortyeight natalizumab 62 hc completed study visits baseline unadjusted mean nbv natalizumab150880cm popescu etal 2013 vs hc153923cm popescu etal 2013 p0033 median baseline t2lv natalizumab172462mm popescu etal 2013 vs hc4420mm popescu etal 2013 p00001 different mean pbvc year 2 adjusted gender baseline age 057 ci 07620 03716 natalizumab 050 07208 02831 hc difference groups statistically significant 0073 p062 2year period hc demonstrated mild improvements cognitive tests vs natalizumab subjects however pros similar two groupsconclusionstable ms patients natalizumab similar brain volume loss people ms suggesting normalization brain atrophy,0.0
targeting central nervous system extracellular vesicles enhanced triiodothyronine remyelination effect experimental autoimmune encephalomyelitis bioact mater 2021 jul 24 9373384 doi 101016 jbioactmat202107017 ecollection 2022 marabstractthe lack targeted highefficiency drug delivery central nervous system cns nidus main problem treatment demyelinating disease extracellular vesicles evs possess great promise drug delivery vector given advanced features however clinical applications limited inadequate targeting ability dilution effects systemic administration neural stem cells nscs supply plentiful source evs account extraordinary capacity selfrenewal developed novel therapeutic system using evs modified nscs high expressed ligand pdgfa evps achieve local delivery demonstrated evps greatly enhance target capability oligodendrocyte lineage moreover evps used embedding triiodothyronine t3 thyroid hormone critical oligodendrocyte development serious side effects systemically administered results demonstrated systemic injection evps + t3 versus evps t3 administration individually markedly alleviated disease development enhanced oligodendrocyte survival inhibited myelin damage promoted myelin regeneration lesions experimental autoimmune encephalomyelitis mice taken together findings showed engineered evps possess remarkable cns lesion targeting potential offers potent therapeutic strategy cns demyelinating diseases well neuroinflammationpmid34820577 pmcpmc8586265 doi101016 jbioactmat202107017,1.0
lungs fire pilot study 18ffdg pet ct idiopathicinflammatorymyopathyrelated interstitial lung disease background interstitial lung disease ild rapid progression rp main contributors unfavourable outcomes patients idiopathic inflammatory myopathy iim study aimed identify clinical value pet ct scans iimild patients construct predictive model rpildmethodsadult iimild patients hospitalized four divisions first affiliated hospital zhejiang university school medicine fahzju 1 january 2017 31 december 2020 reviewed pet ct scans characteristics patients met inclusion exclusion criteria collected analysedresultsa total 61 iimild patients enrolled study twentyone patients 344 developed rpild 24 patients 393 died followup false discovery rate fdr correction percentpredicted diffusing capacity lung carbon monoxide dlco p 0014 bilateral lung mean standard uptake value suvmean p 0014 abnormal mediastinal lymph node p 0045 significantly different rpild nonrpild groups subsequent univariate multivariate logistic regression analyses verified findings dlm model established including three values predict rpild cutoff value 2 area curve auc 0905 higher bilateral lung suvmean p 0019 spleen suvmean p 0011 observed iimild patients died within 3 months moderate correlation recognized two valuesconclusionselevated bilateral lung suvmean abnormal mediastinal lymph nodes decreased dlco significantly associated rpild iimild patients dlm model valuable predicting rpild requires validation,0.0
determinants disability development patients multiple sclerosis abstract background multiple sclerosis ms one common chronic neurological diseases affecting central nervous system young adults objective investigate demographic clinical factors effective development irreversible disability onset ms identify factors affect transformation relapseremitting ms rrms phase progressive ms pms phase methods retrospective study 741 patients diagnosed rrms pms according mcdonald criteria enrolled turkish ms database department neurology ms polyclinic faculty medicine karadeniz technical university trabzon turkey kaplanmeier analysis used evaluate time taken reach edss 4 edss 6 onset disease time taken edss 4 edss 6 results age onset 40 years polysymptomatictype onset pyramidal bladderintestinal systemrelated first episode 7 episodes first 5 years 2 years first two episodes found effective ms patients reach edss 4 edss 6 demographic clinical parameters effective progression edss 4 edss 6 pyramidal bladderintestinal systemrelated first episode 46 episodes first 5 years 2 years start first treatment smoking conclusions findings reveal important characteristics ms patients region however associations parameters ms pathophysiology remain elucidated,1.0
correction bortezomib antinmdar encephalitis following daclizumab treatment patient multiple sclerosis bmj neurol open 2021 jul 23 3 2 e000096corr1 doi 101136 bmjno2020000096corr1 ecollection 2021abstract corrects article doi 101136 bmjno2020000096 pmid34396130 pmcpmc8313866 doi101136 bmjno2020000096corr1,0.0
intraoperative monitoring visual evoked potentials patients undergoing transsphenoidal surgery pituitary adenoma systematic review background transsphenoidal surgery gold standard pituitary adenoma resection although rare serious complication surgery worsened vision postoperativelyobjectiveto determine whether patients undergoing transsphenoidal surgery pituitary adenoma intraoperative monitoring visual evoked potentials vep safe reproducible effective technological adjunct predicting postoperative visual functionmethodsthe pubmed ovid platforms searched january 1993 december 2020 identify publications 1 featured patients undergoing transsphenoidal surgery pituitary adenoma 2 used intraoperative optic nerve monitoring vep 3 reported safety effectiveness reference lists crosschecked expert opinion sought identify publicationsresultseleven studies included comprising ten case series one prospective cohort study employed techniques improve reliability safety issues reported comparative study included described statistically significant improvement postoperative visual field testing vep monitoring used remaining caseseries varied conclusion nine studies surgical manipulation halted event vep amplitude decrease suggesting widespread consensus warning sign injury anterior optic apparatusconclusionsdespite limited lowquality published evidence regarding intraoperative vep monitoring review suggests safe reproducible increasingly effective technique predicting postoperative visual deficits studies specific transsphenoidal surgery required determine utility protecting visual function resection complex pituitary tumours,0.0
vitro studies nasal formulations nanostructured lipid carriers nlc solid lipid nanoparticles sln pharmaceuticals basel 2021 jul 23 14 8 711 doi 103390 ph14080711abstractthe nasal route used many years local treatment nasal diseases recently route gaining momentum due possibility targeting central nervous system cns nasal cavity avoiding bloodbrain barrier bbb area use lipid nanoparticles nanostructured lipid carriers nlc solid lipid nanoparticles sln nasal formulations shown promising outcomes wide array indications brain diseases including epilepsy multiple sclerosis alzheimers disease parkinsons disease gliomas herein state art recent literature available vitro studies nasal formulations lipid nanoparticles discussed specific vitro cell culture models needed assess cytotoxicity nasal formulations explore underlying mechanism s drug transport absorption across nasal mucosa addition different studies 3d nasal casts reported showing ability predict drug deposition nasal cavity evaluating factors interfere process nasal cavity area type administration device angle application inspiratory flow presence mucoadhesive agents among others notwithstanding preclude use confirmatory vivo studies significant impact 3r replacement reduction refinement principle within scope animal experiments expected use 3d nasal casts test nasal formulations lipid nanoparticles still totally unexplored authors best knowledge thus constituting wide open field researchpmid34451808 doi103390 ph14080711,0.0
singlecell alternative polyadenylation analysis delineates gabaergic neuron types background alternative polyadenylation apa emerging important mechanism posttranscriptional regulation gene expression across eukaryotic species recent studies shown apa plays key roles biological processes cell proliferation differentiation singlecell rnaseq technologies widely used gene expression heterogeneity studies however systematic studies apa singlecell level still lackingresultshere described novel computational framework sapas utilizes 3tagbased scrnaseq data identify novel poly sites quantify apa singlecell level applying sapas scrnaseq data phenotype characterized gabaergic interneurons identified cell typespecific apa events different gabaergic neuron types genes cell typespecific apa events enriched synaptic architecture communications observed strong enrichment heritability several psychiatric disorders brain traits altered 3 utrs coding sequences cell typespecific apa events finally exploring modalities apa discovered bimodal apa pattern pak3 classify chandelier cells different subpopulations different laminar positionsconclusionswe established method characterize apa singlecell level applied scrnaseq dataset gabaergic interneurons singlecell apa analysis identified cell typespecific apa events also revealed modality apa classify cell subpopulations thus sapas will expand understanding cellular heterogeneity,0.0
musicbased therapy rehabilitation people multiple sclerosis systematic review clinical trials abstract background multiple sclerosis ms major cause chronic neurological disability young adults increasing number controlled studies assessed potential rehabilitative effects new drugfree treatments complementary standard care including musicbased therapy mbt objective analyze evidence effectiveness mbt within therapeutic approaches individuals diagnosed ms methods systematic review clinical trials performed searches following databases biosis cinahl cochrane ebsco eric google scholar ibecs lilacs lisa proquest medline pedro psycinfo apa psychological behavioral pubmed scielo scopus sportdiscus web science clinical trials comparing mbt versus conventional therapy intervention included results 282 studies identified 10 trials selected among total sample consisted 429 individuals 253 allocated experimental group mbt 176 control group conventional therapies intervention studies presented high methodological quality modalities mbt clustered four groups 1 rhythmic auditory 2 playing musical instruments 3 dance strategy 4 neurological music therapy overall studies consistently showed mbt better conventional therapy intervention regard gait parameters double support time walking speed fatigue level fatigability coordination dexterity balance walking endurance lower extremity functional strength emotional status pain regarding mental fatigability memory data conflicting evidence unclear conclusion mbt safe effective approach clinical rehabilitation ms patients leads positive results regarding motor nonmotor functions,0.0
preliminary study application renal ultrasonography radiomics classification glomerulopathy background aim study investigate potential use renal ultrasonography radiomics features histologic classification glomerulopathymethodsa total 623 renal ultrasound images 46 membranous nephropathy mn 22 iga nephropathy patients collected cases images divided training group 51 cases 470 images test group 17 cases 153 images total 180 dimensional features designed extracted renal parenchyma ultrasound images least absolute shrinkage selection operator lasso logistic regression applied normalized radiomics features select features highest correlations four machine learning classifiers including logistic regression support vector machine svm random forest knearest neighbour classifier deployed classification mn iga nephropathy subsequently results assessed according accuracy receiver operating characteristic roc curvesresultspatients mn older patients iga nephropathy mn primarily manifested patients nephrotic syndrome whereas iga nephropathy presented mainly nephritic syndrome analysis classification performance four classifiers iga nephropathy mn revealed random forest achieved highest area roc curve auc 07639 highest specificity 08750 however logistic regression attained highest accuracy 07647 highest sensitivity 08889 conclusionsquantitative radiomics imaging features extracted digital renal ultrasound fully capable distinguishing iga nephropathy mn radiomics analysis noninvasive method helpful histological classification glomerulopathy,0.0
structure human c9orf72smcr8 complex reveals multivalent protein interaction architecture plos biol 2021 jul 23 19 7 e3001344 doi 101371 journalpbio3001344 online ahead printabstracta major cause familial amyotrophic lateral sclerosis als frontotemporal dementia ftd spectrum disorder hexanucleotide g4c2 repeat expansion first intron c9orf72 gene many underlying mechanisms lead manifestation disease include toxic gain function repeat g4c2 rnas dipeptide repeat proteins reduction c9orf72 gene product c9orf72 protein interacts smcr8 wdr41 form trimeric complex regulates multiple cellular pathways including autophagy report structure c9orf72smcr8 complex 38 resolution using singleparticle cryoelectron microscopy cryoem structure reveals 2 distinct dimerization interfaces c9orf72 smcr8 involves extensive network interactions homology c9orf72smcr8 folliculinfolliculin interacting protein 2 flcnfnip2 gtpase activating protein gap complex enabled identification key residue within active site smcr8 structural analysis suggested coiledcoil region within udenn domain smcr8 act interaction platform coiledcoil proteins deletion reduced interaction c9orf72smcr8 complex fip200 upon starvation summary study contributes toward understanding biological function c9orf72smcr8 complexpmid34297726 doi101371 journalpbio3001344,0.0
multidimensional longitudinal systems profiling reveals predictive pattern severe covid19 iscience 2021 jun 19102752 doi 101016 jisci2021102752 online ahead printabstractcovid19 respiratory tract infection can affect multiple organ systems predicting severity clinical outcome individual patients major unmet clinical need remains challenging due intra interpatient variability longitudinally profiled integrated 150 clinical laboratory immunological parameters 173 patients mild fatal covid19 using systems biology detected progressive dysregulation multiple parameters indicative organ damage correlated disease severity particularly affecting kidneys hepatobiliary system immune landscape performing unsupervised clustering trajectory analysis identified t b cell depletion early indicators complicated disease course addition markers hepatobiliary damage emerged robust predictor lethal outcome critically ill patients allowed us propose novel clinical covid19 severity cost score distinguishes complicated disease trajectories predicts lethal outcome critically ill patientspmid34179733 pmcpmc8213514 doi101016 jisci2021102752,0.0
constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis c57bl 6 mice background constipation common gastrointestinal dysfunction potential impact peoples immune state quality life investigated effects constipation experimental autoimmune encephalomyelitis eae animal model multiple sclerosis ms methodsconstipation induced loperamide female c57bl 6 mice alternations gut microbiota permeability intestinal barrier bloodbrain barrier histopathology colon assessed constipation induction eae induced constipation mice fecal microbiota transplantation fmt performed constipation mice microbiotadepleted mice clinical scores histopathology inflammation demyelination treg th17 treg17 teff17 imbalance peripheral lymphatic organs central nervous system cytokines include tgf gmcsf il10 il17a il17f il21 il22 il23 serum assessed different groupsresultscompared vehicle group constipation mice showed gut microbiota dysbiosis colon inflammation injury increased permeability intestinal barrier bloodbrain barrier found clinical pathological scores constipation eae mice severer eae mice compared eae mice constipation eae mice showed reduced percentage treg treg17 cells increased percentage th17 teff17 cells decreased ratio treg th17 treg17 teff17 spleen inguinal lymph nodes brain spinal cord moreover serum levels tgf il10 il21 decreased gmcsf il17a il17f il22 il23 increased constipation eae mice addition pathological processes transferred via gut microbiotaconclusionsour results verified constipation induced gut microbiota dysbiosis exacerbated eae via aggravating treg th17 treg17 teff17 imbalance cytokines disturbance c57bl 6 mice,1.0
aryl hydrocarbon receptordependent tgfalpha vegfb ratio correlates disease subtype prognosis multiple sclerosis neurol neuroimmunol neuroinflamm 2021 jul 23 8 5 e1043 doi 101212 nxi0000000000001043 print 2021 julabstractobjective evaluate aryl hydrocarbon receptor ahr dependent transforming growth factor alpha tgf vascular endothelial growth factor b vegfb ratio regulates effects metabolic dietary microbial factors acute chronic cns inflammation potential marker multiple sclerosis ms methods tgf vegfb ahr agonistic activity determined serum 252 patients relapsingremitting rr ms primary secondary progressive ms well active disease clinically isolated syndrome cis rrms relapse results tgf vegfb ratio ahr agonistic activity decreased ms subgroups stable disease course compared controls active cns inflammation cis rrms relapse tgf vegfb ratio ahr agonistic activity increased conversely patients minimal clinical impairment despite longstanding disease tgf vegfb ratio ahr agonistic activity unaltered finally tgf vegfb ratio ahr agonistic activity correlated neurologic impairment time conversion cis msconclusions ahrdependent tgf vegfb ratio altered subtype severity disease activityspecific manner correlates time conversion cis ms may thus represent novel marker serve additive guideline immunomodulatory strategies msclassification evidence study provides class iii evidence serum levels ahr tgf vegfb distinguish subtypes ms predict severity disease activity mspmid34301821 doi101212 nxi0000000000001043,0.0
dopaminergic dysregulation syndromic autism spectrum disorders insights genetic mouse models front neural circuits 2021 jul 23 15700968 doi 103389 fncir2021700968 ecollection 2021abstractautism spectrum disorder asd neurodevelopmental disorder defined altered social interaction communication repetitive restricted inflexible behaviors approximately 152 general population meet diagnostic criteria asd several brain regions including cortex amygdala cerebellum basal ganglia implicated asd pathophysiology midbrain dopamine system important modulator cellular synaptic function multiple asdimplicated brain regions via anatomically functionally distinct dopaminergic projections dopamine hypothesis asd postulates dysregulation dopaminergic projection pathways contribute behavioral manifestations asd including altered reward value social stimuli changes sensorimotor processing motor stereotypies review examine support idea cellautonomous changes dopaminergic function core component asd pathophysiology discuss human literature supporting involvement altered dopamine signaling asd including genetic brain imaging pharmacologic studies focus genetic mouse models syndromic neurodevelopmental disorders single gene mutations lead increased risk asd highlight studies directly examined dopamine neuron number morphology physiology output models overall find considerable support idea dopamine system may dysregulated syndromic asds however appear consistent signature models show increased dopaminergic function others deficient dopamine signaling conclude dopamine dysregulation common syndromic forms asd specific changes may unique genetic disorder may account full spectrum asdrelated manifestationspmid34366796 pmcpmc8343025 doi103389 fncir2021700968,0.0
transcriptomic profiling high lowspiking regions reveals novel epileptogenic mechanisms focal cortical dysplasia type ii patients abstractfocal cortical dysplasia fcd malformation cerebral cortex poorlydefined epileptogenic zones ezs poor surgical outcome fcd associated inaccurate localization ez hence identifying novel epileptogenic markers aid localization ez patients fcd much needed highthroughput gene expression studies fcd samples potential uncover molecular changes underlying epileptogenic process identify novel markers delineating ez purpose first time performed rna sequencing surgically resected paired tissue samples obtained electrocorticographically graded high max low spiking min regions fcd type ii patients autopsy controls identified significant changes max samples fcd type ii patients compared nonepileptic controls case min samples found significant enrichment myelination oligodendrocyte development differentiation neuronal axon ensheathment phospholipid metabolism cell adhesion cytoskeleton semaphorins ion channels max region integration max vs nonepileptic control max vs min rna sequencing rna seq data plp1 pllp ugt8 klk6 sox10 mog mag mobp anln ermn spp1 cldn11 tnc gpr37 slc12a2 abca2 abca8 aspa p2rx7 cers2 map4k4 tf ctgf semaphorins opalin fgfs calb2 tnc identified potential key regulators multiple pathways related fcd type ii pathology identified novel epileptogenic marker elements may contribute epileptogenicity patients fcd possible markers localization ez,1.0
mscopilot new smartphonebased digital biomarkers correlate expanded disability status scale scores people multiple sclerosis abstractbackgrounda previous clinical study showed high specificity sensitivity reliability mscopilot software medical device designed ad scientiam selfassessment people multiple sclerosis pwms compared traditional multiple sclerosis functional composite msfc conducted analyses assess mscopilotnulls performance respect expanded disability status scale edss methodsthe data 116 pwms analysed studied correlations mscopilot scores edss ability distinguish pwms high low edss study distribution digital test scores well logistic regression models analyses performed using msfc testsresultsmscopilot composite scores highly correlated edss r 065 p001 msfc counterparts confirming known correlation msfc edss linear regression framework walking digital tests good explanatory power especially pwms edss35 radj047 mean values mscopilot subscore significantly different patients edss35 others p005 proved msfc cognition tests mscopilot4 best model predict edss score35 auc092 conclusionthese analyses confirm reliability mscopilot show interesting correlations edss similar results obtained msfc mscopilot able highlight nuances different stages ms msfc capture,1.0
association nlrp3 rs35829419 rs10754558 polymorphisms risks autoimmune diseases systematic review metaanalysis front genet 2021 jul 22 12690860 doi 103389 fgene2021690860 ecollection 2021abstractthe existing knowledge association nlrp3 rs35829419 rs10754558 polymorphisms susceptibility autoimmune diseases aids remains controversial herein metaanalysis performed evaluate association searched databases relevant studies published english february 2021 stata14 used assess odds ratio nlrp3 rs35829419 significant association overall aids found three genetic models vs c 95ci 089 069114 ac vs cc 100 077130 aa ac vs cc 093 071120 however subgroup analysis disease type showed nlrp3 rs35829419 allele may significant protective effect rheumatoid arthritis ra susceptibility vs c 074 057096 nlrp3 rs10754558 polymorphism contributes significantly reduce risk aids allelic model g vs c 078 071087 homozygote codominant model gg vs cc 063 051077 heterozygote codominant model gc vs cc 078 066091 dominant model gg gc vs cc 073 063084 recessive model gg vs gc cc 073 062088 subgroup analysis ethnicity association observed nlrp3 rs10754558 g allele aids latin americans european arabian asian populations stratification disease type showed significant association nlrp3 rs10754558 g allele type 1 diabetes t1d ra systemic lupus erythematosus sle celiac disease cd multiple sclerosis ms myasthenia gravis mg metaanalysis suggests nlrp3 rs10754558 rs35829419 polymorphism associated susceptibility aids especially latin american individualspmid34367252 pmcpmc8340881 doi103389 fgene2021690860,0.0
high level serum cerebrospinal fluid heparan sulfate hyaluronic acid might biomarker severity neuromyelitis optica front immunol 2021 jul 22 12705536 doi 103389 fimmu2021705536 ecollection 2021abstractbackground neuromyelitis optica nmo multiple sclerosis ms autoimmune glial fibrillary acidic protein gfap astrocytopathy idiopathic inflammatory demyelinating diseases iidds mainly present encephalomyelitis heparan sulfate hs hyaluronic acid ha two components glycocalyx carbohydraterich layer surface blood vessels mediates interaction blood degradation glycocalyx nmo poorly understoodpurpose detect serum cerebrospinal fluid csf levels shed hs ha correlate levels disease severity determine diagnostic valuemethods obtained serum csf samples 24 nmo patients 15 ms patients 10 autoimmune gfap astrocytopathy patients 18 controls without noninflammatory neurological diseases soluble hs ha ifn il17a matrix metalloproteinase mmp 1 detected via elisaresults serum csf levels hs ha related cytokines plasma mmp1 significantly elevated diseases notably hs ha levels positively correlated expanded disability status scale scoresconclusions results indicate glycocalyx degradation inflammation nmo ms autoimmune gfap astrocytopathy moreover increased shedding hs ha may indicate worse clinical situation furthermore therapeutic strategies protect glycocalyx may effective diseasespmid34367165 pmcpmc8339917 doi103389 fimmu2021705536,1.0
effectiveness healthcare resource utilization adherence subcutaneous interferon beta1a according age patients multiple sclerosis cohort study using us claims database front neurol 2021 jul 22 12676585 doi 103389 fneur2021676585 ecollection 2021abstractbackground thought older patients multiple sclerosis ms may present different clinical disease phenotype therefore respond subcutaneous interferon beta1a sc ifn 1a differently younger patients however realworld data available concerning effectiveness sc ifn 1a according age using data us claims databases cohort analysis aimed determine differences relapse rates healthcare utilization treatment adherence discontinuation according predefined age groups methods patient data pooled ibm marketscan commercial claims database medicare supplemental database patients confirmed ms diagnosis initiated treatment sc ifn 1a july 01 2010 december 31 2015 along least 6 months continuous enrolment healthcare plan followed first prescription index date date discontinuation treatment switch end observation period 1 year index date results 5 340 patients included analysis high proportion patients free relapse across age groups range 941954 numerical decrease number mri performed age mean 025 1830 years 020 3140 years 016 4150 years 014 51 years adherence 80 seen increase age 776 1830 years 796 3140 years 813 4150 years 840 51 years time nonsignificant decrease discontinuation incidence rate 7991 7301 7175 6871 conclusion effectiveness sc ifn 1a appear reduced consequence age realworld setting older patients lower discontinuation rates reduced disease activity reflected lower relapse rates fewer mri scans compared younger patientspmid34381411 pmcpmc8351462 doi103389 fneur2021676585,0.0
twelve months feasibility trial reflections three experiences public patient involvement research hrb open res 2021 jan 28 411 doi 1012688 hrbopenres132051 ecollection 2021abstractin open letter present reflections three different perspectives integration public patient involvement ppi research trial reflect experience patient employed contract researcher prior research experience feasibility trial cognitive rehabilitation multiple sclerosis open letter written ppi research team member reflections researcher trial principle investigator will discuss changes made impacts resulted ppi input trial focus ppi involvement participant recruitment development trial material integration ppi along research cycle collaboration hope open letter will encourage principle investigators groups include ppi members part research team help patients members public understand experience ppi members likepmid34381956 pmcpmc8320708 doi1012688 hrbopenres132051,0.0
cognitive dysfunction multiple sclerosis educational level protective factor neurol int 2021 jul 22 13 3 335342 doi 103390 neurolint13030034abstractmost people ms experience cognitive deficits especially attention memory information processing executive functions negatively impacting quality life cognitive variables shortterm memory logical memory verbal fluency 65 patients multiple sclerosis ms analysed conjunction sociodemographic variables sex age educational level might influence disease progression found psychoeducational variables exerted significant effect cognitive status patients ms thus considering sex age educational level type ms spms rrms tests betweensubject effects revealed statistically significant differences three cognitive variables addition found type ms time since onset also generated significant cognitive differences study shows educational achievement level protective factor disease acting source intellectual enrichment promotes cognitive reserve patients ms longitudinal studies assessing disease progression prognosis patients ms useful order determine specific importance variables patients strategies enhance performance neuropsychological assessment taskspmid34449709 doi103390 neurolint13030034,0.0
effectiveness equineassisted therapies improving health outcomes people multiple sclerosis systematic review metaanalysis abstractbackgroundscientific evidence shown equineassisted therapies eat lead improvements physical function quality life qol people disabilities practice hippotherapy therapeutic riding tr need confirm whether people multiple sclerosis pwms can also benefit practice review aimed systematically evaluate metaanalyze available data potential health benefits eat pwmsmethodsfour electronic databases medline pubmed web science sportdiscus scopus searched systematically inception june 2021 randomized controlled trials rcts comparative studies provided information regarding effects eat pwms studiesnull methodological quality assessment performed using pedro minors scales metaanalysis heterogeneity across studies quantified using i2 statistic fixedeffect randomeffects models applied obtain pooled results case low i2 30 high i2 30 heterogeneity values respectively standardized mean differences smd 95 confidence intervals cis calculated assess change outcomeresultsafter removing duplicated studies 234 results retrieved literature search 11 eligible full text search finally 9 studies methodological quality ranging good low quality met inclusion criteria six focused hippotherapy 4 included quantitative analysistotally 225 pwms patients evaluated findings metaanalysis indicated therapy improved static smd 042 95 ci 005 078 dynamic balance smd 051 95 ci 004 106 significant benefits observed patientsnull qol smd 037 95 ci 000 073 hippotherapy showed effectiveness reducing selfperceived fatigue smd 070 95 ci 033 107 tr showed mixed effects balance qolconclusionthe actual evidence effectiveness eat pwms mainly limited hippotherapy rehabilitation approach seems beneficial effects static balance qol fatigue directly gait dynamic balance altogether findings suggest hippotherapy incorporated complementary therapy developing comprehensive care plans pwms,0.0
cerebrospinal fluid oligoclonal immunoglobulin gamma bands longterm disability progression multiple sclerosis retrospective cohort study sci rep 2021 jul 22 11 1 14987 doi 101038 s4159802194423xabstractmultiple sclerosis ms patients immunoglobulin gamma igg oligoclonal bands ocb cerebrospinal fluid csf different genetic backgrounds brain mri features compared without study aimed determine whether csfocb status associated longterm disability outcomes used swedish ms register data clinically definite ms patients known ocb status date birth age ms onset time sustained expanded disability status scale edss milestones 3 4 6 time conversion secondary progressive sp ms sex immunomodulatory treatment imts duration collected multivariate cox regression models used investigate association ocb status risk reaching milestone ocbpositive group reached disability milestones earlier time younger age ocbpositivity significantly increased risk reaching edss 30 hr 129 95 ci 112 148 p 0001 40 hr 138 95 ci 117 163 p 0001 ocbpositive group 20 higher risk conversion spms csfocb presence associated higher risk reaching edss milestones conversion spms findings suggest higher disease modifying effect ocb presence early inflammatory stages mspmid34294805 doi101038 s4159802194423x,0.0
vaccination multiple sclerosis patients treated highly effective diseasemodifying drugs overview consideration cladribine tablets ther adv neurol disord 2021 jul 22 1417562864211019598 doi 101177 17562864211019598 ecollection 2021abstractinfectious diseases important consideration autoimmune conditions multiple sclerosis infective episodes may trigger relapses significantly deteriorate course disease immunotherapies may cause increased rates infectionrelated adverse events thus infection vaccinerelated issues included individualized patientspecific treatment strategy counseling starting therapy regularly treatment clinical epidemiological studies well pharmacovigilance data repeatedly demonstrated safety great majority vaccines multiple sclerosis patients moreover studies shown vaccinations killed inactivated vaccines increase shortterm risk relapse deterioration multiple sclerosis whereas infections shown provoke relapses available evidence indicates reduced humoral vaccination efficacy treatment ms drugs acting s1p receptor natalizumab bcell depleting therapies recent data cladribine tablets suggest potential effective immunization interval two treatment courses completion therapy regardless treatment vaccine efficacy may optimized proper timing application multiple sclerosis patients receiving highly effective therapies vaccinated according general recommendations healthy adults immunization covid19 highly recommended multiple sclerosis patients regardless age comorbidities preliminary data show potential adequate responses patients treated cladribine tabletspmid34671422 pmcpmc8521756 doi101177 17562864211019598,0.0
emerging role neutrophils autoimmuneassociated disorders effector predictor therapeutic targets medcomm beijing 2021 jul 22 2 3 402413 doi 101002 mco269 ecollection 2021 sepabstractneutrophils essential components immune system vital roles pathogenesis autoimmune disorders effector cells neutrophils promote autoimmune disease releasing cytokines chemokines cascades accompany inflammation neutrophil extracellular traps nets regulating immune responses cellcell interactions recent evidence extended functions neutrophils accumulating evidence implicated neutrophils contribute tissue damage broad range disorders involving rheumatoid arthritis ra systemic lupus erythematosus sle primary sjgrens syndrome pss multiple sclerosis ms crohns disease cd gout variety studies reported functional role neutrophils therapeutic targets autoimmune diseases however challenges controversies field remain enhancing understanding neutrophils role autoimmune disorders may advance development new therapeutic approachespmid34766153 pmcpmc8554667 doi101002 mco269,0.0
metabolic landscapes sarcomas abstractmetabolic rewiring offers novel therapeutic opportunities cancer recently scant information regarding soft tissue sarcomas due heterogeneous tissue origin histological definition underlying genetic history novel largescale genomic metabolomics approaches now helping stratify physiopathology review show various genetic alterations skew activation pathways orient metabolic rewiring sarcomas provide update contribution newly described mechanisms metabolic regulation underscore mechanisms relevant sarcomagenesis shared cancers discuss diverse metabolic landscapes condition tumor microenvironment antisarcoma immune responses prognosis finally review current attempts control sarcoma growth using metabolitetargeting drugs,0.0
combined prevalence classified rare rheumatic diseases almost double ankylosing spondylitis background rare diseases rds affect less 5 10 000 people europe fewer 200 000 individuals united states rheumatology rds heterogeneous lack systemic classification clinical courses involve variety diverse symptoms patients may misdiagnosed receive appropriate treatment objective study identify classify important rds rheumatology also attempted determine combined prevalence precisely define area rheumatology increase awareness rds healthcare systems conducted comprehensive literature search analyzed disease specified criteria clinical symptoms treatment regimens prognoses point prevalences epidemiological data available estimated prevalence 1 1 000 000 total point prevalence rds rheumatology estimated sum individually determined prevalencesresultsa total 76 syndromes diseases identified including vasculitis vasculopathy n 15 arthritis arthropathy n 11 autoinflammatory syndromes n 11 myositis n 9 bone disorders n 11 connective tissue diseases n 8 overgrowth syndromes n 3 others n 8 76 diseases 61 80 classified chronic remittingrelapsing course 27 cases 35 upon adequate treatment another 34 45 diseases predominantly progressive difficult control corticosteroids therapeutic option 49 64 syndromes mortality variable determined precisely epidemiological studies prevalence data available 33 syndromes diseases additional eight diseases incidence data accessible summed prevalence rds 288 10 000conclusionsrds rheumatology frequently chronic progressive present variable symptoms treatment options often restricted corticosteroids presumably scarcity randomized controlled trials estimated combined prevalence significant almost double ankylosing spondylitis 18 10 000 thus healthcare systems assign rds similar importance common disease rheumatology,0.0
identification molecular biomarkers associated disease progression testis bulls infected besnoitia besnoiti abstractbreeding bulls infected besnoitia besnoiti may develop sterility either acute chronic infection aim study investigate molecular pathogenesis b besnoiti infection prognosis value bull sterility accordingly five wellcharacterized groups naturally experimentally infected males selected study based clinical signs lesions compatible b besnoiti infection serological results parasite detection broad panel molecular markers representative endothelial activation fibrosis investigated complemented histopathological approach included conventional histology immunohistochemistry results indicated predominance intense inflammatory infiltrate composed mainly resident recruited circulating macrophages lesser extent cd3+ cells infected bulls addition biomarkers associated acute chronic subclinical bovine besnoitiosis testicular parenchyma showed higher number differentially expressed genes natural infections acute chronic infections versus scrotal skin experimental infections subclinical infection subclinical infections genes downregulated except ccl24 cxcl2 genes upregulated contrast acute phase mainly characterized upregulation il1 il6 timp1 whereas chronic phase upregulation icam downregulation mmp13 plat il1 relevant findings macrophages responsible highest level gene regulation testicular parenchyma severely affected sterile bulls genes prognostic markers sterility,0.0
targeting nuclear receptors neurodegeneration neuroinflammation j med chem 2021 jul 12 doi 101021 acsjmedchem1c00186 online ahead printabstractnuclear receptors also known ligandactivated transcription factors regulate gene expression upon ligand signals present attractive therapeutic targets especially chronic diseases despite therapeutic relevance nuclear receptors various pathologies potential neurodegeneration neuroinflammation insufficiently established perspective gathers preclinical clinical data potential role individual nuclear receptors future targets alzheimers disease parkinsons disease multiple sclerosis concomitantly evaluates level medicinal chemistry targeting proteins considerable evidence suggests high promise ligandactivated transcription factors counteract neurodegenerative diseases particularly high potential several orphan nuclear receptors however potent tools lacking orphan receptors limited central nervous system exposure insufficient selectivity also compromises suitability wellstudied nuclear receptor ligands functional studies medicinal chemistry efforts needed develop dedicated highquality tool compounds therapeutic validation nuclear receptors neurodegenerative pathologiespmid34251209 doi101021 acsjmedchem1c00186,0.0
n6methyladenosine rna modification cerebrospinal fluid novel potential diagnostic biomarker progressive multiple sclerosis background progressive multiple sclerosis pms uncommon severe subtype ms worsens gradually leads irreversible disabilities young adults currently applicable reliable biomarkers distinguish pms relapsingremitting multiple sclerosis rrms previous studies demonstrated dysfunction n6methyladenosine m6a rna modification relevant many neurological disorders thus aim study explore diagnostic biomarkers pms based m6a regulatory genes cerebrospinal fluid csf methodsgene expression matrices downloaded arrayexpress database identified differentially expressed m6a regulatory genes ms nonms patients ms clusters identified consensus clustering analysis next analyzed correlation clusters clinical characteristics random forest rf algorithm applied select key m6arelated genes support vector machine svm used construct diagnostic gene signature receiver operating characteristic roc curves plotted evaluate accuracy diagnostic model addition csf samples ms nonms patients collected used external validation evaluated m6a rna methylation quantification kit realtime quantitative polymerase chain reactionresultsthe 13 central m6a rna methylation regulators upregulated ms patients compared nonms patients consensus clustering analysis identified two clusters significantly associated ms subtypes next divided 61 ms patients training set n 41 test set n 20 rf algorithm identified eight feature genes svm method successfully applied construct diagnostic model roc curves revealed good performance finally analysis 11 csf samples demonstrated rrms samples exhibited significantly higher levels m6a rna methylation higher gene expression levels m6arelated genes pms samplesconclusionsthe dynamic modification m6a rna methylation involved progression ms potentially represent novel csf biomarker diagnosing ms distinguishing pms rrms early stages disease,0.0
predicting aggressive multiple sclerosis intrathecal igm synthesis among patients clinically isolated syndrome neurol neuroimmunol neuroinflamm 2021 jul 22 8 5 e1047 doi 101212 nxi0000000000001047 print 2021 julabstractobjective determine best method measure intrathecal immunoglobulin ig m synthesis itms biomarker worse prognosis multiple sclerosis ms compared ability predicting poor evolution 4 methods assessing itms igm oligoclonal bands ocmbs lipidspecific ocmbs lsocmbs reibergram igm index patients clinically isolated syndrome cis methods prospective study consecutive patients performed referral ms center used unadjusted multivariate cox regressions predicting second relapse expanded disability status scale edss scores 4 6 development secondary progressive ms spms results total 193 patients included median interquartile range age 31 2538 years median followup 129 years among methods ocmb lsocmb reibergram significantly identified patients risk preestablished outcomes lsocmb technique strongest associations adjusted hazard ratio ahr lsocmb predicting second relapse 250 95 ci 172364 p 0001 risk reaching edss scores 4 6 spms significantly higher among patients lsocmb ahr 296 95 ci 154571 p 0001 ahr 496 95 ci 2221107 p 0001 ahr 231 95 ci 108493 p 003 respectively conclusions itms predicts aggressive ms disease onset especially detected lsocmbclassification evidence study provides class ii evidence lipidspecific igm oligoclonal bands can predict progression cis ms worse disease course followup least 2 yearspmid34301819 doi101212 nxi0000000000001047,0.0
exosomal delivery therapeutic modulators bloodbrain barrier promise pitfalls abstractnowadays large population around world especially elderly suffers neurological inflammatory degenerative disorders diseases current drug delivery strategies facing different challenges presence bbb limits transport various substances cells brain parenchyma additionally low rate successful cell transplantation brain injury sites leads efforts find alternative therapies stem cell byproducts exosomes touted natural nanodrug carriers 50100 nm diameter nanosized particles harbor transfer plethora therapeutic agents biological cargos brain nanoparticles offer solution maintain paracrine celltocell communications healthy inflammatory conditions main question existence intact bbb limit exosomal trafficking bbb possess molecular mechanisms facilitate exosomal delivery compared circulating cell although preliminary studies shown exosomes cross bbb exact molecular mechanism s beyond phenomenon remains unclear review tried compile facts exosome delivery bbb propose mechanisms regulate exosomal cross pathological physiological conditions,0.0
exposuresafety analyses nintedanib patients chronic fibrosing interstitial lung disease background nintedanib reduces rate decline forced vital capacity patients idiopathic pulmonary fibrosis ipf chronic fibrosing interstitial lung diseases ilds progressive phenotype systemic sclerosisassociated ild sscild recommended dose nintedanib 150 mg twice daily bid methodsdata phase ii iii trials ipf phase iii trials sscild progressive fibrosing ilds ipf analyzed investigate relationship nintedanib plasma concentrations exposure safety liver enzyme elevations defined transaminase elevations equal greater 3 times upper limit normal diarrhea resultsusing data 1403 subjects ipf treated 50150 mg nintedanib bid parametric timetofirstevent model liver enzyme elevations established besides exposure gender significant covariate threefourfold higher exposureadjusted risk females males subsequent analysis combined data ipf sscild n 576 progressive fibrosing ild n 663 studies suggested consistent exposureliver enzyme elevation relationship across studies exposurediarrhea relationship found using data various fibrosing ilds diarrhea risk dependent dose administeredconclusionsthe positive correlation exposure risk liver enzyme elevations consistent across nintedanib studies ipf sscild progressing fibrosing ilds ipf effect size warrant priori dose adjustment patients altered plasma exposure excluding hepatic impairment patients specific labelling recommendations diarrhea dose administered better predictor exposure,0.0
sarcopenia associates snap25 snps mirnas profile modulated structured rehabilitation treatment background sarcopenia loss muscle mass strength causing disability morbidity mortality older adults characterized alterations neuromuscular junctions nmjs snap25 essential maintenance nmj integrity expression protein shown modulated snap25 rs363050 polymorphism number mirnasmethodswe analysed parameters cohort sarcopenic patients undergoing structured rehabilitation rs363050 genotype frequency distribution analyzed 177 sarcopenic patients 181 healthy controls hc concentration seven mirnas mir451a mir4255p mir1555p mir4213p mir4953p mir7445p mir935p identified mouse brain mirnome analysis differentially expressed wild type compared snap25 heterozygous mice analyzed well droplet digital pcr ddpcr subgroup severe sarcopenic patients undergoing rehabilitationresultsthe snap25 rs363050 aa genotype significantly common sarcopenic patients compared hc pc 001 mir451a significantly upregulated patients rehabilitation rehabilitation modified mirnas expression mir1555p mir4213p mir451a mir4255p mir7445p mir935p expression significantly upregulated p 001 whereas mir4953p significantly downregulated p 0001 rehabilitation notably rehabilitationassociated improvement muscleskeletal sppb score significantly associated reduction mir451a expressionconclusionthese results support hypothesis role snap25 sarcopenia suggest snap25associated mirnas circulatory biomarkers rehabilitative outcome sarcopenia,0.0
informed road map prevention alzheimer disease call arms abstractalzheimer disease ad prevention trials hold promise delay prevent cognitive decline dementia onset intervening significant neuronal damage occurs recent years first ad prevention trials launched yielding important findings biology targeting asymptomatic ad pathology however limitations impact design prevention trials including translation animal models recapitulate key stages multiple pathological aspects human disease missing target validation asymptomatic disease uncertain causality association pathophysiologic changes cognitive clinical symptoms limited biomarker validation novel targets field accelerating advancements key areas including development highly specific quantitative biomarker measures ad pathology increasing understanding course relationship amyloid tau pathology asymptomatic symptomatic stages development powerful interventions can slow reverse ad amyloid pathology review current status prevention trials propose key areas needed research call basic translational scientists accelerate ad prevention specifically review 1 sporadic dominantly inherited primary secondary ad prevention trials 2 proposed targets mechanisms drugs including amyloid tau inflammatory pathways combination treatments 3 need appropriate prevention animal models experiments 4 biomarkers outcome measures needed design human asymptomatic prevention trials conclude actions needed effectively move prevention targets trials forward,0.0
downstream effects polypathology neurodegeneration medial temporal lobe subregions abstractthe medial temporal lobe mtl nidus neurodegenerative pathologies therefore important region study polypathology investigated associations neurodegenerative pathologies thickness different mtl subregions measured using highresolution postmortem mri tau tar dnabinding protein 43 tdp43 amyloid synuclein pathology rated scale 0 absent 3 severe hippocampus entorhinal cortex erc 58 individuals without neurodegenerative diseases median age 750 years 603 male thickness measurements erc brodmann area ba 35 36 parahippocampal cortex subiculum cornu ammonis ca 1 stratum radiatum lacunosum moleculare srlm derived 02 02 02 mm3 postmortem mri scans excised mtl specimens contralateral hemisphere using semiautomated approach spearmans rank correlations performed neurodegenerative pathologies thickness correcting age sex hemisphere including four proteinopathies model found significant associations 1 tdp43 thickness subregions r 027 r 046 2 tau ba35 r 031 srlm thickness r 033 amyloid tdp43 negative cases found strong significant associations tau erc r 040 ba35 r 055 subiculum r 042 ca1 thickness r 047 unique dataset shows widespread mtl atrophy relation tdp43 pathology atrophy regions affected early braak stageing tau pathology moreover strong association tau thickness early braak regions absence amyloid suggests role primary agerelated tauopathy neurodegeneration,0.0
effects variable frequencies kinesthesia balance agility exercise program adults knee osteoarthritis study protocol randomized controlled trial background knee osteoarthritis oa common painful disabling condition affects older individuals proprioceptive training programs form kinesthesia balance agility kba exercises reported beneficial individuals knee oa however optimal training dosage kba exercises still unclear aim study determine effects different frequencies kba training ie twiceweekly thriceweekly adults knee oamethodsa single assessor blind threearm parallel multicenter randomized controlled trial will conducted one hundred twenty adults knee oa will recruited four tertiary hospitals northwestern nigeria randomly assigned one three intervention groups twiceweekly kba n 40 thriceweekly kba n 40 conventional physiotherapy n 40 ratio 111 participants conventional physiotherapy group will receive two sessions brief patient education sixteen sessions ultrasound therapy stretching strengthening exercises 8 weeks participants two different kba groups will receive kba training according designed sessions 8 weeks addition conventional physiotherapy program groups will assessed preintervention immediately postintervention 3 months 4 months 6 months postrandomization primary outcome will physical function ibadan knee hip osteoarthritis outcome measure whereas secondary outcomes will pain intensity visual analogue scale pain knee stability knee outcome surveyactivities daily living scale proprioception electronic goniometer quality life osteoarthritis knee hip quality life questionnaire discussionthe findings study may provide evidence effectiveness kba exercise training ideal number sessions needed achieve highest effectiveness adults knee oatrial registration pan african clinical trials registry pactr201810713260138 registered 28 november 2017,0.0
covid19 vaccine hesitancy adults multiple sclerosis united states follow survey initial vaccine rollout 2021 abstractbackgroundmultiple sclerosis ms organizations recommended adults ms obtain covid19 vaccination vaccine hesitancy barrier full covid19 inoculation general population whether vaccine hesitancy also barrier towards optimizing vaccination rates ms community unknown investigate vaccine hesitancy inform efforts increase vaccine uptake ms population conducted follow survey national sample adults ms living united states completed initial survey early covid19 pandemic current study aimed answer questions vital understanding vaccine hesitancy specifically 1 prevalence covid19 vaccine hesitancy early 2021 2 reasons factors associated current hesitancy 3 vaccine willingness hesitancy changed april may 2020 january february 2021 4 changed vaccine willingnessmethodsadults ms living united states n359 completed two online surveys first 10 april 2020 06 may 2020 second 11 january 2021 08 february 2021 willingness intent obtain covid19 vaccine participants also completed measures assess factors potentially related vaccine hesitancy including demographics ms variables influenza vaccine history vaccine concerns contextual factors including perceived risk sarscov2 infection trust covid19 information source anxiety lonelinessresultsof participants completed second survey early 2021 203 vaccine hesitant either reporting undecided 139 intending get vaccinated 64 vaccine hesitancy decreased two surveys nearly threefourths 738 second sample reporting planned obtain covid19 vaccine vaccine hesitancy associated lower level education nonwhite recent flu vaccination holding lower perception onenulls risk getting covid19 lower trust centers disease control prevention participants vaccine hesitant reported concerns longterm effects vaccine vaccine approval process potential impact vaccine given health conditions history notably 90 undecided group wanted additional information vaccine deciding vaccine willingness changed time many somewhat willing willing get covid19 vaccine survey 2 individuals unwilling survey 1 highly likely remain unwilling survey 2conclusionoverall covid19 vaccine hesitancy decreased pandemic although one five adults ms hesitant early 2021 undecided indicated wanted additional information vaccine deciding whether vaccinated suggesting additional educational efforts vaccinenulls safety longterm effects potential health implications still needed findings indicate public health efforts may best focused undecided whose vaccine hesitancy may change time possibly appropriate information intervention,0.0
validity singleleg heel raise test people multiple sclerosis crosssectional study front neurol 2021 jul 21 12650297 doi 103389 fneur2021650297 ecollection 2021abstractbackground singleleg heel raise test common clinical assessment however little known validity people multiple sclerosis ms study investigated validity singleleg heel raise test group people ms healthy control group ctl materials methods twentyone people ms 49 12 years expanded disability status scale 1555 10 healthy controls 48 12 years performed singleleg heel raise test ankle plantarflexion isometric strength assessment using electromechanical dynamometry mobility measures timed 25foot walk 2min walk test functional stair test results convergent validity heel raise test strength moderate participants ms completing 20 heel raises r 063 p 0001 weak entire sample r 030 p 0020 compared average ctl group values heel raise test differentiated groups ms groups weaker p 0001 stronger p 0003 limbs strength differentiated groups weaker limb p 0010 considering weaker strong limbs ms group ctl group average values mobility measures moderatetostrong correlations heel raise test weaker ms limb + ctl r 071078 stronger ms limb + ctl r 062070 weaktomoderate correlations strength weaker ms limb + ctl r 049058 p 00010007 discussion people ms singleleg heel raise test may clinically useful identified impaired muscle performance differentiated muscle performance healthy control group together control group correlated functional mobilitypmid34354656 pmcpmc8333614 doi103389 fneur2021650297,0.0
neuroprotective effects curcumin cerebral ischemia cellular molecular mechanisms acs chem neurosci 2021 jul 12 doi 101021 acschemneuro1c00153 online ahead printabstractdespite major global health concern cerebral ischemia stroke limited therapeutic options tissue plasminogen activator tpa available medication manage acute ischemic stroke medication associated adverse effects narrow therapeutic time window curcumin polyphenol abundantly present rhizome turmeric plant curcuma longa shown promising neuroprotective effects animal models neurodegenerative diseases including cerebral ischemia central nervous system cns neuroprotective effects curcumin experimentally validated alzheimers disease parkinsons disease multiple sclerosis cerebral ischemia curcumin can exert pleiotropic effects postischemic brain including antioxidant antiinflammatory antiapoptotic vasculoprotective direct neuroprotective efficacies importantly neuroprotective effects curcumin reported ischemic hemorrhagic stroke models broadspectrum neuroprotective efficacy curcumin suggested curcumin can appealing therapeutic strategy treat cerebral ischemia review aimed address pharmacotherapeutic potential curcumin cerebral ischemia including cellular molecular mechanisms neuroprotection revealing curcumin appealing therapeutic candidate cerebral ischemiapmid34251185 doi101021 acschemneuro1c00153,1.0
cannabis autoimmunity possible mechanisms action immunotargets ther 2021 jul 21 10261271 doi 102147 itts267905 ecollection 2021abstractmedical cannabis mc describes usually inhaled ingested use cannabis plant cannabis extract medicinal purposes action whole cannabis plants extremely complex large number active compounds bind plethora different receptors also interact synergistically otherwise renewed interest medicinal properties cannabis led increasing research practical uses cannabis derivatives found endocannabinoid system particularly cb2 receptor activation possible target treatment inflammatory autoimmune diseases related immune cell activation however vivo findings still lack creating difficulties applying translational cannabinoid research human immune functions review summarized main mechanisms action medical cannabis plant especially regarding immune system endocannabinoid system looking preliminary clinical data three important autoimmune diseases three different specialities rheumatoid arthritis multiple sclerosis inflammatory bowel diseasepmid34322454 pmcpmc8313508 doi102147 itts267905,1.0
mir99a regulates cd4+ tcell differentiation attenuates experimental autoimmune encephalomyelitis mtormediated glycolysis mol ther nucleic acids 2021 jul 21 2611731185 doi 101016 jomtn202107010 ecollection 2021 dec 3abstractmultiple micrornas exhibit diverse functions regulate inflammatory autoimmune diseases microrna99a mir99a shown involved adipose tissue inflammation downregulated inflammatory lesions autoimmune diseases rheumatoid arthritis systemic lupus erythematosus study found mir99a downregulated cd4+ t cells experimental autoimmune encephalomyelitis eae mice animal model multiple sclerosis overexpression mir99a alleviated eae development promoting regulator t cells inhibiting t helper type 1 th1 cell differentiation bioinformatics functional analyses revealed antiinflammatory effects mir99a attributable role negatively regulating glycolysis reprogramming cd4+ t cells targeting mtor pathway additionally mir99a expression induced transforming growth factor tgf regulate cd4+ t cell glycolysis differentiation taken together results characterize pivotal role mir99a regulating cd4+ t cell differentiation glycolysis reprogramming eae development may indicate mir99a promising therapeutic target amelioration multiple sclerosis possibly autoimmune diseasespmid34820151 pmcpmc8598972 doi101016 jomtn202107010,1.0
multiplestate monitoring sod1 amyloid formation singleresidue resolution rheonmr spectroscopy j chem soc 2021 jul 7 doi 101021 jacs1c02974 online ahead printabstractformation protein aggregates fibrils entails conversion soluble native protein monomers via multiple molecular states spectroscopic techniques succeeded capturing transient molecularscale events fibrillation situ report residue statespecific realtime monitoring fibrillation amyotrophic lateral sclerosisrelated sod1 rheology nmr rheonmr spectroscopy moderately denaturing conditions nmr signals folded unfolded monomeric sod1 simultaneously observable crosspeak intensities folded monomeric sod1 decreased faster unfolded species 310helix folded sod1 deformed prior global unfolding furthermore realtime protein dynamics analysis identified residues involved core structure formation sod1 oligomers findings provide insight local global unfolding events sod1 fibril formation rheonmr analysis will applicable atomiclevel monitoring amyloidogenic proteins also quantification shearinduced structural changes nonamyloidogenic proteins elucidation shearenhanced chemical phenomena viscosity increase crystallization various solutionstate compoundspmid34232041 doi101021 jacs1c02974,0.0
multiple sclerosis incidence prevalence poland data administrative health claims abstractbackgroundthe detailed data concerning multiple sclerosis ms epidemiology poland based studies less populated provinces therefore evaluated ms incidence prevalence poland using electronic administrative health claims ahcs national health fundmethodswe retrospectively analyzed ahc financial database collected 2009 2019 encompassing patients using public health resources three different algorithms identification ms cases used based studies performed german population type 1 tested united states type 2 one created purpose study type 3 required least 3 ahcs since 2009 g35 icd10 diagnosis outpatient specialist care hospitalization rehabilitation service combination within maximally 3 years first last ahc provided least one ahc either neurological outpatient care hospitalization neurological ward prescription diseasemodifying therapy american algorithm type 2 required 3 ahcs within analyzed year german algorithm type 1 required one ahc analyzed yearresultsaccording type 3 algorithm ageadjusted ms incidence prevalence 2019 66 1312 100 000 inhabitants respectively 2014 2019 significant trend increasing prevalence decreasing incidence ms observed p0001 median age prevalent ms patients 50 years interquartile range iqr 3961 whereas median age incident ms cases 37 years iqr 2848 femaletomale ratio ms patients 24 according type 1 algorithm ageadjusted ms incidence prevalence 2019 116 2449 100 000 inhabitants respectively use type 2 algorithm resulted estimated ageadjusted ms incidence prevalence values 2019 62 1201 100 000 inhabitants respectivelyconclusionsmultiple sclerosis incidence prevalence poland higher previously reported similar numbers shown central european countries,0.0
highdose biotin multiple sclerosis systematic review metaanalysis randomized controlled trials abstractbackgroundbiotin may activate acetylcoa 3methylcrotonylcoa propionylcoa pyruvate carboxylases increase myelin repair synthesis may enhance production adenosine triphosphate atp may essential prevent neurodegeneration purpose review determine effectiveness safety highdose biotin hdb multiple sclerosis via systematic review randomized controlled trialsmethodswe searched following electronic databases relevant articles medline central embase scopus clinicaltrialsgov website april 2021 considered randomized clinical trials rcts involved adult patients diagnosed phenotype multiple sclerosis conforms mcdonald 2010 2017 criteria lublin 2014 criteria included studies employing highdose biotin md1003 administered orally least 300 mg day given least three months methodological quality assessment included studies done using cochrane risk bias rob tool grade approach used assess certainty evidence coe resultsout 366 records identified three rcts involving 889 individuals diagnosed ms 830 participants progressive ms pms 59 rrms pooled analyses overall femalemale ratio 1161 included trials used hdb adjunctive treatment risks bias three studies low across domains 12 15 months insufficient evidence hdb placebo arms differed terms composite improvement msrelated disability relative risk rr 287 95 ci 0292840 2 trials 796 participants i266 low coe improvement expanded disability status scale iedss rr 227 95 ci 0252098 2 trials 796 participants i263 low coe iedss improvement 25foot walk time itw25 iedssitw25 rr 058 95 ci 017200 2 trials 796 participants i213 moderate coe among patients pms pooled data itw25 12 15 months yielded statistical significance rr 206 95 ci 104409 2 trials 796 participants i20 moderate coe favoring hdb among patients pms 12 15 months significant differences found terms mean change edss md 006 95 ci 014002 2 studies 796 participants 889 participants i268 among patients pms synthesized data incidence aes rr 098 95 ci 092104 3 trials i20 high coe serious aes rr 098 95 ci 077124 3 trials 889 participants i20 moderate coe significantly different hdb placebo groups 662 pooled patients hdb group 31 patients 47 found laboratory test interference compared zero event pooled placebo group high coe conclusionsa moderate certainty evidence suggests potential benefit favor hdb administered 12 15 months terms itw25 patients pms however important tradeoff benefit high certainty evidence suggesting increased incidence laboratory test interference hdb taken,1.0
multiple sclerosis pregnancy role female fertility systematic review jbra assist reprod 2020 nov 5 doi 105935 1518055720210022 online ahead printno abstractpmid34061482 doi105935 1518055720210022,0.0
premyelinating oligodendrocytes mechanisms underlying cell survival integration front cell dev biol 2021 jul 21 9714169 doi 103389 fcell2021714169 ecollection 2021abstractin central nervous system oligodendrocytes produce myelin sheaths enwrap neuronal axons provide trophic support increase conduction velocity new oligodendrocytes produced throughout life process referred oligodendrogenesis oligodendrogenesis consists three canonical stages oligodendrocyte precursor cell opc premyelinating oligodendrocyte preol mature oligodendrocyte ol however generation oligodendrocytes inherently inefficient process following precursor differentiation majority premyelinating oligodendrocytes lost likely due apoptosis premyelinating oligodendrocytes progress survival checkpoint generate new myelinating oligodendrocytes process termed integration review will explore intrinsic extrinsic signaling pathways influence preol survival integration examining intrinsic apoptotic pathways metabolic demands interactions neurons astrocytes microglia premyelinating oligodendrocytes additionally will discuss similarities maturation newly generated neurons premyelinating oligodendrocytes finally will consider increasing survival integration preols potential increase remyelination multiple sclerosis deepening understanding premyelinating oligodendrocyte biology may open door new treatments demyelinating disease will help paint clearer picture new oligodendrocytes produced throughout life facilitate brain functionpmid34368163 pmcpmc8335399 doi103389 fcell2021714169,1.0
specificity anticitrullinated protein antibodies citrullinated enolase peptides function epitope structure composition antibodies basel 2021 jul 21 10 3 27 doi 103390 antib10030027abstractrheumatoid arthritis ra autoimmune disease affecting approximately 12 world population addition first discovered serologic markers ra rheumatoid factors rfs anticitrullinated protein antibodies acpas even specific disease compared rfs found 7080 ra patient sera ra etiopathogenesis still needs elucidated different factors proposed involved epsteinbarr virus infection hence understanding interaction acpas citrullinated peptide targets relevant better knowledge ra pathophysiology diagnostic purposes study cohort ra sera healthy control sera multiple sclerosis sera screened reactivity variety citrullinated peptides originating enolase profilaggrin proteoglycan epsteinbarr nuclear antigen2 enzymelinked immunosorbent assay acpa reactivity citrullinated enolase peptides found depend peptide length peptide conformation favouring cyclic disulfide bond conformations long peptides linear peptides truncated ones additional investigations optimal peptide conformation acpa detection employing profilaggrin ebna2 peptides confirmed findings indicating positive effect cyclization longer peptides approximately 20 amino acids moreover screening citrullinated peptides confirmed acpas can divided two groups based reactivity approximately 90 ra sera recognize several peptide targets defined crossreactive overlapping reactivities whose reactivity citrullinated peptide considered primarily backbonedependent contrast approximately 10 recognize single target defined nonoverlapping primarily depending specific amino acid sidechains epitope stable interaction collectively study contributed characterize epitope composition structure optimal acpa reactivity obtain knowledge crossreactive nature acpaspmid34449533 doi103390 antib10030027,0.0
isolation microglia analysis protein expression flow cytometry avoiding pitfall microglia background autofluorescence bio protoc 2021 jul 20 11 14 e4091 doi 1021769 bioprotoc4091 ecollection 2021 jul 20abstractmicroglia unique type tissueresident innate immune cell found within brain spinal cord retina healthy nervous system main functions defend tissue infectious microbes support neuronal networks synapse remodeling clear extracellular debris dying cells phagocytosis many existing microglia isolation protocols require use enzymatic tissue digestion magnetic beadbased isolation steps increase time cost procedures introduce variability experiment report protocol generate singlecell suspensions freshly harvested murine brains spinal cords efficiently dissociates tissue removes myelin debris simple mechanical dissociation density centrifugation can applied rat nonhuman primate tissues describe importance including empty channels downstream flow cytometry analyses microglia singlecell suspensions accurately assess expression protein targets highly autofluorescent cell type methodology ensures observed fluorescence signals incorrectly attributed protein target interest appropriately taking account unique autofluorescence cell type phenomenon already present young animals increases aging levels comparable observed antibodies highly abundant antigenspmid34395729 pmcpmc8329471 doi1021769 bioprotoc4091,1.0
oligodendrocytes microglia key players myelin development damage repair biomolecules 2021 jul 20 11 7 1058 doi 103390 biom11071058abstractoligodendrocytes myelinmaking cells cns regulate complex process myelination physiological pathological conditions significantly aided glial cell types microglia brainresident macrophagelike innate immune cells review summarize oligodendrocytes orchestrate myelination especially myelin repair damage present novel aspects oligodendroglial functions emphasize contribution microglia generation regeneration myelin discussing beneficial detrimental roles especially remyelination underlining cellular molecular components involved finally present recent findings towards human stem cellderived preclinical models study microglia human pathologies role microbiome glial cell functionspmid34356682 doi103390 biom11071058,1.0
danshensu inhibits il1induced inflammatory response chondrocytes osteoarthritis possibly via suppressing nfb signaling pathway abstractpurposeosteoarthritis oa common inflammatory disease associated pain cartilage destruction interleukin il 1 widely used induce inflammatory response oa models study aimed explore role danshensu dss il1induced inflammatory responses oamethodsil1 used induce chondrocyte inflammation cell viability evaluated cell counting kit8 cck8 assay il6 cox2 tnf inos mrna levels detected qrtpcr mmp3 mmp13 adamts4 adamts5 aggrecan collagen pib pp65 protein levels detected western blot oa mouse model established surgical destabilization medial meniscus dmm osteoarthritis research society international oarsi score evaluated stainingresultsdss affect levels inflammatory indicators including il6 cox2 tnf inos peg2 suppressed cox2 inos protein expression il1 treated chondrocytes addition dss downregulated il1enhanced expression mmp3 mmp13 adamts4 adamts5 upregulated aggrecan collagen expression moreover dss significantly inhibited il1induced phosphorylation pib pp65 dosedependent manner chondrocytes suggesting plays role nfb signaling pathway furthermore dss significantly reduced dmminduced cartilage oarsi score mice demonstrating protective role oa progression vivoconclusionsour study revealed protective role dss oa suggesting dss might act potential treatment oa,0.0
fecal microbiota transplantation microbiome modulation technique alzheimer#39 s disease cureus 2021 jul 20 13 7 e16503 doi 107759 cureus16503 ecollection 2021 julabstractalzheimers disease ad common form dementia fifth leading cause death among elderly ad involves parts brain can lead progressive memory loss impaired language skills cognitive thinking affecting ones ability carry daily activities aging bad dietary habits family history well altered gut microbiota composition may play role pathogenesis ad although association imbalance gut microbiota ad still difficult determine suggested dysbiosis can lead increased secretion lipopolysaccharides amyloid may impair permeability intestine bloodbrain barrier moreover can progress process neuroinflammation amyloidbeta formation ultimately neuronal death microbiotatargeted interventions personalized diet probiotics fecal microbiota transplantation fmt might represent potential therapeutic option ad review article discusses procedure fmt possible side effects recipients body addition review role fmt context application various nervous systemrelated disorders ad parkinsons disease multiple sclerosis pmid34430117 pmcpmc8374998 doi107759 cureus16503,0.0
wearable robotic gait training persons multiple sclerosis satisfaction study sensors basel 2021 jul 20 21 14 4940 doi 103390 s21144940abstractwearable exoskeletons showed improvements levels disability quality life people neurological disorders however important understand users perspectives aim study explore patients physiotherapists satisfaction gait training ekso gt exoskeleton people multiple sclerosis ms crosssectional study 54 participants conducted clinical data selfadministered scales data registered patients performed sessions ekso gt evaluate patients satisfaction quebec user evaluation assistive technology client satisfaction questionnaire used high level satisfaction reported patients physiotherapists moderate correlation found number sessions patients satisfaction score rho 0532 p 0001 excellent correlation physiotherapists time experience neurology rehabilitation satisfaction possibility combining device gait trainings approaches rho 0723 p 0003 study demonstrates good degree satisfaction people ms 313 570 40 physiotherapists 3850 367 45 points ekso gt effectiveness safety impact patients gait highly rated characteristics ekso gt features comfort weight device improved patients perspectivespmid34300677 doi103390 s21144940,0.0
tcell responses sarscov2 multiple sclerosis patients treated ocrelizumab healed covid19 absent low antispike antibody titers abstractbackgrounddisease modifying therapies multiple sclerosis ms can impair specific immune response severe acute respiratory syndrome coronavirus2 sarscov2 specifically recognized ocrelizumab reduces abrogates antisarscov2 antibody production natural infection vaccination little known tcell responsesmethodswe developed interferon ifn release assay igra detect tcell responses specific sarscov2 overnight stimulation whole blood peptide libraries covering immunodominant sequence domains spike glycoprotein s nucleocapsid phosphoprotein n resultsfive patients ms receiving ocrelizumab treatment least 1 year recovered sarscov2 infection enrolled study despite absence low concentration antis antibodies tcell response detectable five ms patients results accordance marked reduction peripheral blymphocyte absolute counts induced ocrelizumab conversely affect peripheral blood tlymphocyte subset absolute relative counts cd4 cd8 ratioconclusionsthe detection specific tcell responses sarscov2 patients receiving bcell depleting therapies represents useful tool improve diagnostic approach sarscov2 infection accurately assess immunological response natural infection vaccination,1.0
expression pathogenic analysis integrin family genes systemic sclerosis front med lausanne 2021 jul 20 8674523 doi 103389 fmed2021674523 ecollection 2021abstractobjectives emerging evidence shows integrin members involved inflammation fibrosis systemic sclerosis ssc study aimed evaluating expression integrin family genes skin tissue ssc patients exploring potential pathogenic mechanism methods utilized public datasets ssc skin tissue gene expression omnibus geo database analyze expression clinical significance integrin family genes ssc expression integrin members skin tissue also assessed immunohistochemistry addition functional enrichment pathway analysis conducted results compared healthy controls mrna protein levels itga5 itgb2 itgb5 upregulated skin ssc patients analysis indicated mrna expression levels itga5 itgb2 itgb5 positively correlated modified rodnan skin thickness score mrss functional enrichment pathway analysis showed integrin members may play multiple roles pathogenesis ssc among itga5 itgb2 itgb5 might synergistically promote ssc affecting extracellular matrix ecm turnover ecmreceptor interaction focal adhesion leukocyte transendothelial migration itga5 itgb5 also might affect angiogenesis endothelial cell function addition itga5 itgb2 itga5 associated different pathways respectively itga5 uniquely enriched actin organization itgb5 tgf signaling itgb2 immune cell activation conclusion results implied abnormal expression integrin family genes including itga5 itgb2 itgb5 may participate multiple pathological processes ssc investigations required confirming speculationpmid34355002 pmcpmc8329247 doi103389 fmed2021674523,0.0
ventilatory efficiency pulmonary vascular diseases eur respir rev 2021 jul 20 30 161 200214 doi 101183 1600061702142020 print 2021 sep 30abstractcardiopulmonary exercise testing cpet frequently used tool differential diagnosis dyspnoea ventilatory inefficiency defined high minute ventilation v e relative carbon dioxide output v co2 hallmark characteristic pulmonary vascular diseases contributes exercise intolerance disability patients mechanisms ventilatory inefficiency multiple include high physiologic dead space abnormal chemosensitivity altered carbon dioxide co2 setpoint normal v e v co2 makes pulmonary vascular disease pulmonary arterial hypertension pah chronic thromboembolic pulmonary hypertension cteph unlikely finding high v e v co2 without alternative explanation prompt diagnostic testing exclude pah cteph particularly patients risk factors prior venous thromboembolism systemic sclerosis family history pah patients established pah cteph v e v co2 may improve interventions prognostic marker however studies needed clarify added value assessing ventilatory inefficiency longitudinal followup patientspmid34289981 doi101183 1600061702142020,0.0
reduction fatigue symptoms following administration nutritional supplements patients multiple sclerosis med sci basel 2021 jul 20 9 3 52 doi 103390 medsci9030052abstractdespite recent advances immunemodulatory drugs pharmacological therapies proven ineffective severe presentations multiple sclerosis ms including secondary progressive ms present therapeutic interventions performance primarily focused ameliorating symptoms improve patients quality life qol among complementary treatments nutrition considered decisive factor control symptoms enhance wellness ms patients although special diets associated ms impact diet dietary supplements course progressive forms disease studied last years fatigue among common disabling symptoms reported ms patients fatigue defined multiple sclerosis council clinical practice guidelines msccpg 1998 subjective lack physical mental energy individual perceives interference habitual desired activities study aimed compare psychometric functioning fatigue severity scale fss modified fatigue impact scale mfis sample people ms specifically chronic treatment change two parameters two vitaminrich dietary supplements citozym ergozym evaluated impact nutritional supplements revealed differences antioxidant antiinflammatory parameters among volunteers treatment group subsequent improvement fatigue conclusion results obtained confirmed effectiveness complementary nutritional therapies evaluated essentially based hematological biomarkers possible act disability improve qol ms patientspmid34287336 doi103390 medsci9030052,1.0
association msrelated knowledge health literacy selfefficacy resilience quality life large cohort ms community members crosssectional study abstractbackground despite potential importance little known associations multiple sclerosis ms knowledge outcomes among ms community membersobjective examine relationships msrelated knowledge health literacy selfefficacy resilience quality life qol ms symptom severity cohort ms community membersmethods crosssectional study n1993 assessed cohort understanding ms online course enrolees using means standard deviations evaluated impact participant characteristics outcomes using chi square ttests linear regression models assessed associations outcomes using pearson correlationresults found total cohort moderate high scores outcomes people living ms average mean ms knowledge score average qol resilience health literacy scores association ms status outcome scores supported linear regression models ms knowledge correlated outcome either people living ms without msconclusions ms knowledge associated study outcomes suggesting educational interventions solely aim increase knowledge may ineffective improving healthrelated outcomes within ms community,0.0
correction ostkamp et al sunlight exposure exerts immunomodulatory effects reduce multiple sclerosis severity proc natl acad sci u s 2021 jul 20 118 29 e2110306118 doi 101073 pnas2110306118no abstractpmid34253619 doi101073 pnas2110306118,0.0
obesity pediatriconset multiple sclerosis french cohort study neurol neuroimmunol neuroinflamm 2021 jul 20 8 5 e1044 doi 101212 nxi0000000000001044 print 2021 julabstractobjective study link high body mass index bmi childhood occurrence pediatriconset multiple sclerosis poms compare within ms population clinicalradiologicbiological characteristics according bmimethods casecontrol study comparing bmi data 60 patients poms 39 girls 21 boys bictre hospital 113 nonneurologic controls nncs 68 girls 45 boys 18 614 healthy controls hcs 9 271 girls 9 343 boys performed crude bmi cbmi residual bmi rbmi measured bmi expected bmi age zscore rbmi sd adult equivalent categories international obesity task force 25 overweight 30 obese assessedresults boys cbmi rbmi significantly higher patients poms compared nncs cbmi +29 rbmi +295 p 001 hcs cbmi +204 p 001 girls cbmi rbmi differ poms nncs patients cbmi p 04 rbmi p 044 hcs cbmi +099 p 001 csf inflammatory markers increased bmi prepubertal patients p 001 whereas vitamin d level diagnosis lower boys higher bmi p 0016 increased bmi associated clinical radiologic disease characteristicsconclusions overweight obesity frequently observed diagnosis particularly boys poms compared nonneurologic controls french hcs moreover bmi related initial inflammation csf prepubertal patients poms suggesting interaction excess body fat sexual hormones poms occurrencepmid34285094 doi101212 nxi0000000000001044,0.0
italian translation psychometric validation abilhand26 correlation upper limb objective subjective measures multiple sclerosis subjects abstractbackgroundupper limb ul function affected 50 people multiple sclerosis pwms last decade patient reported outcome measures prom playing important role clinical trial practice abilihand26 prom assess selfperceived manual ability defined capacity manage daily activities using upper limbs aim study translate abilhand26 italian explore psychometric properties examining associations demographics clinical variables 9hole peg test 9hpt manual ability measures36 mam36 materials methodssubjects recruited five italian neurological centers evaluated abilhand26 9hpt mam36 confirmatory factor analysis rasch analysis adopted investigate psychometric properties abilhand26resultstwo hundred fortyfive patients recruited rasch analyses showed adequate functioning supported unidimensionality scale abilhand26 showed negative correlations age disease duration moderate negative correlation edss 9hpt scores arms strong positive associations 84 mam36 difference abilhand26 scores emerged comparing patients severe disability edss6 patients either mild moderate disability t comapring relapsingremitting secondary progressive patientsconclusionthe italian version abilhand26 now available shows adequate reliability score moderate criterion validity strong convergent validity abilhand26 represent valid assessment selfperceived ability perform manual activity especially pwms moderatetohigh level disability,0.0
biomedical knowledge graph system propose mechanistic hypotheses realworld environmental health observations cohort study informatics application jmir med inform 2021 jul 20 9 7 e26714 doi 102196 26714abstractbackground knowledge graphs common form knowledge representation biomedicine many fields developed open biomedical knowledge graphbased system termed reasoning biomedical objects linked knowledge oriented pathways robokop robokop consists frontend user interface backend knowledge graph robokop user interface allows users posit questions explore answer subgraphs users can also posit questions direct cypher query underlying knowledge graph currently contains roughly 6 million nodes biomedical entities 140 million edges predicates describing relationship nodes drawn 30 curated data sourcesobjective aimed apply robokop survey data workplace exposures immunemediated diseases environmental polymorphisms registry epr within national institute environmental health sciencesmethods analyzed epr survey data identified 45 associations workplace chemical exposures immunemediated diseases selfreported study participants n 4574 20 associations significant p05 false discovery rate correction used robokop 1 validate associations determining whether plausible connections exist within robokop knowledge graph 2 propose biological mechanisms might explain serve hypotheses subsequent testing highlight following three exemplar associations carbon monoxidemultiple sclerosis ammoniaasthma isopropanolallergic diseaseresults robokop successfully returned answer sets three queries posed context driving examples answer sets included potential intermediary genes well supporting evidence might explain observed associationsconclusions demonstrate realworld application robokop generate mechanistic hypotheses associations workplace chemical exposures immunemediated diseases expect robokop will find broad application across many biomedical fields scientific disciplines due generalizability speed discovery generation mechanistic hypotheses open naturepmid34283031 doi102196 26714,0.0
drugrelated demyelinating syndromes understanding risk factors pathophysiological mechanisms magnetic resonance imaging findings abstractsome drugs medications can precipitate immune system deregulations might confused recurrent demyelinating diseases multiple sclerosis ms neuromyelitis optica spectrum disorders nmo exacerbations existing disease neoplastic lesions conditions narrative review describe relevant drugs medications associated iatrogenic demyelination anthelminthic agent levamisole frequent cocaine adulterant can precipitate exacerbated immune response attacking central nervous system cns highefficacy multiple sclerosis ms drugs might induce selective cns immunosuppression making susceptible opportunistic infections course demyelination progressive multifocal leukoencephalopathy sometimes interruption highefficacy drug treat ms can induce rapid cns reentry lymphocytes exacerbating demyelinating processes triggering rebound syndromes furthermore selective cytokines inhibition antitnf agents might induce imbalance cell death proliferation inducing paradoxical increase cns tumor necrosis factor tnf affecting activity lymphocytes microglia macrophages triggering aberrant inflammation demyelination immune checkpoint inhibitors new class antineoplastic drugs enhance immune response tumor cells upregulation tcell activity however hyperactivation immune system might associated induction unwanted autoimmune responses paper review risk factors possible pathological mechanisms magnetic resonance imaging mri findings drugrelated demyelinating syndromes,1.0
healthrelated quality life amyotrophic lateral sclerosis using eq5d5l background study aimed appraise healthrelated quality life hrqol measured fivelevel euroqol5 dimensions eq5d5l amyotrophic lateral sclerosis als explore associations nonmotor symptoms mood changes cognitive disturbances sleep disturbances methodseq5d5l descriptive scores converted single aggregated health utility score calibrated visual analog scale eqvas used selfrating current health status multiple logistic regression analysis used explore factors associated hrqolresultsamong 547 enrolled als patients assessed using eq5d5l highest frequency reported problems usual activities 767 followed selfcare 688 anxiety depression 620 median health utility score 078 median eqvas score 70 clinical factors corresponding differences eq5d5l health utility score included age onset onset region als functional rating scalerevised alsfrsr score kings college stages patients depression anxiety poor sleep lower health utility scores patients excessive daytime sleepiness rapid eye movement sleep behavior disorder lower eqvas scores multivariate logistic analysis indicated alsfrsr scores depression anxiety associated health utility scores adjusting parameters alsfrsr score stages depression significantly associated eqvas scores p 005 conclusionthis study examined hrqol als patients using chinese version eq5d5l scale across different stages disease found hrqol related disease severity mood disturbances management nonmotor symptoms may help improve hrqol als patients,0.0
safety exercise training multiple sclerosis protocol updated systematic review metaanalysis syst rev 2021 jul 20 10 1 208 doi 101186 s13643021017510abstractbackground exponential growth number clinical research studies regarding exercise training multiple sclerosis literature reviews metaanalyses documented many benefits exercise training research requires careful review documenting safety exercise training multiple sclerosis clarity safety represents major hurdle clinical prescription exercise behaviourobjectives enhance understanding feasibility exercise multiple sclerosis 1 provide protocol systematic review metaanalysis summarises rates risks clinical relapse adverse events ie unfavourable outcome occurs intervention delivery time period serious adverse events ie untoward occurrence results death life threatening requires hospitalisation results disability intervention delivery time period well retention adherence compliance randomised controlled trials exercise training persons multiple sclerosis 2 identify moderators relapse adverse events serious adverse event ratesmethods eight fieldrelevant databases will searched electronically studies involve randomised controlled trial exercise training nonexercise nonpharmacological comparator report safety outcomes include adults multiple sclerosis will included rates relative risks three primary outcomes relapse adverse event serious adverse event will calculated reported standard error 95 confidence interval randomeffects metaanalysis will estimate mean population relative risk outcomes potential sources variability including participant characteristics features exercise stimulus comparison condition will examined randomeffects metaregression maximum likelihood estimationdiscussion results systematic review metaanalysis will inform guide healthcare practitioners researchers policymakers safety exercise training persons multiple sclerosis possible will identify impact exercise type exercise delivery style participant disability level prescription exercise guidelines safety exercise training result will identify critical information safety exercise persons multiple sclerosis also identifying gaps research setting priorities future enquiriessystematic review registration prospero 2020 crd42020190544pmid34284811 doi101186 s13643021017510,0.0
arctigenin exerts neuroprotective effect ameliorating cortical activities experimental autoimmune encephalomyelitis vivo front immunol 2021 jul 19 12691590 doi 103389 fimmu2021691590 ecollection 2021abstractmultiple sclerosis ms chronic disease central nervous system cns characterized inflammatory cells invade brain spinal cord among bulk different ms models widely used best understood rodent model experimental autoimmune encephalomyelitis eae arctigenin botanical extract arctium lappa reported exhibit pharmacological properties including antiinflammation neuroprotection however effects arctigenin neural activity attacked inflammation ms still unclear use twophoton calcium imaging observe activity somatosensory cortex neurons awake eae mice vivo found added hyperactive cells calcium influx network connectivity synchronization mainly preclinical stage eae model besides silent cells decreased calcium influx reduced network synchronization accompanied compensatory rise functional connectivity found remission stage arctigenin treatment restricts inordinate individually neural spiking calcium influx network activity preclinical stage also restores neuronal activity communication remission stage addition confirm frequency ampa receptormediated spontaneous excitatory postsynaptic current sepsc also increased preclinical stage can blunted arctigenin findings suggest excitotoxicity characterized calcium influx involved eae preclinical stage arctigenin exerts neuroprotective effect limiting hyperactivity preclinical stage ameliorates eae symptoms indicating arctigenin potential therapeutic drug neuroprotection msrelated neuropsychological disorderspmid34349758 pmcpmc8327179 doi103389 fimmu2021691590,1.0
biological factors limit sustained remission rheumatoid arthritis bioflare study protocol nonrandomised longitudinal cohort study background knowledge immunemediated inflammatory disease imid aetiology pathogenesis improved greatly recent years however little known factors trigger disease relapses flares converting diseases inactive active states focussing rheumatoid arthritis ra challenge will address imids remit relapse extrapolating pathogenetic factors involved disease initiation new episodes inflammation triggered recurrent systemic immune dysregulation locally factors within joint either endorsed overarching epigenetic factors changes systemic localised metabolismmethodsthe bioflare study nonrandomised longitudinal cohort study aims enrol 150 patients ra remission stable dose nonbiologic diseasemodifying antirheumatic drugs dmards consent discontinue treatment participants stop dmards time 0 offered optional ultrasoundguided synovial biopsy studied intensively blood sampling clinical evaluation weeks 0 2 5 8 12 24 anticipated 50 participants will disease flare whilst 50 remain drugfree remission study duration 24 weeks flaring participants undergo ultrasoundguided synovial biopsy reinstatement previous treatment blood samples will used investigate immune cell subsets activation status cytokine profile autoantibody profiles epigenetic profiles synovial biopsies will examined profile cell lineages subtypes present flare blood urine synovium will examined determine metabolic profiles taking account generated data multivariate statistical techniques will employed develop model predict impending flare ra highlighting therapeutic pathways informative biomarkers despite initial recruitment time target sarscov2 pandemic impacted significantly decision taken close recruitment 118 participants complete datadiscussionthis study aims investigate pathogenesis flare rheumatoid arthritis significant knowledge gap understanding addressing major unmet patient needtrial registrationthe study retrospectively registered 27 06 2019 isrctn registry 16371380,0.0
cohort analysis 67 charcotmarietooth italian patients identification new mutations broadening phenotype expression produced rare variants front genet 2021 jul 19 12682050 doi 103389 fgene2021682050 ecollection 2021abstractcharcotmarietooth cmt disease prevalent inherited motor sensory neuropathy clusters clinically genetically heterogeneous group disorders 90 genes associated different phenotypes goal study identify genetic features recruited cohort patients highlighting role rare variants genotypephenotype correlation enrolled 67 patients applied diagnostic protocol including multiple ligationdependent probe amplification copy number variation cnv detection pmp22 locus nextgeneration sequencing ngs sequencing 47 genes known associated cmt routinely screened medical genetics approach allowed identification 26 patients carrying whole gene cnv pmp22 remaining 41 patients ngs identified causative variants eight patients genes hspb1 mfn2 kif1a gdap1 mtmr2 sh3tc2 kif5a mpz five new vs three previously reported variants three sporadic vs five familial variants familial segregation analysis allowed correctly interpret two variants initially reported variants uncertain significance reclassified pathological cohort reported patient carrying novel familial mutation tail domain kif5a protein domain previously associated familial amyotrophic lateral sclerosis als cmt patient carrying hspb1 mutation previously reported als data indicate combined tools gene association medical genetics allow dissecting unexpected phenotypes associated previously known unknown genotypes thus broadening phenotype expression produced either pathogenic undefined variants clinical trial registration clinicaltrialsgov nct03084224 pmid34354735 pmcpmc8329958 doi103389 fgene2021682050,0.0
effects lower extremity constraintinduced movement therapy gait balance chronic hemiparetic patients stroke description study protocol randomized controlled clinical trial background protocols involving intensive practice shown positive outcomes constraint induced movement therapy cit appears one best options better outcomes upper limb rehabilitation still little data lower extremity constraintinduced movement therapy lecit effects gait balanceobjectiveto evaluate effects lecit protocol gait functionality balance chronic hemiparetic patients following strokemethodsthe study adopts randomized controlled singleblinded study design fortytwo patients suffered stroke chronic phase recovery 6 months gait disability community gait able walk least 10 m without advice support 1 person will randomly allocated 2 groups lecit group control group intensive conventional therapy people will excluded speech deficits render unable understand answer properly evaluation scales exercises selected protocol suffered clinical event screening beginning protocol outcome will assessed baseline t0 immediately intervention t1 6 months t2 outcome measures chosen trial follows 6min walk test 6minwt 10m walk test 10mwt timed go tug 3d gait analysis 3dga mini balance evaluation systems test minibestest secondary measure lower extremity motor activity log will evaluated lemal participants groups will receive 15 consecutive days daily exercise participants lecit group will submitted protocol 25 h day 15 consecutive days will include 1 intensive supervised training 2 use shaping strategy motor training 3 application transfer package plus 30 min control group will receive conventional physiotherapy 25 h day 15 consecutive days period cit intervention repeated measures analyses will made compare differences define clinically relevant changes groupsresultsdata collection currently ongoing results expected 2021discussionlecit seems good protocol inclusion stroke survivors rehabilitation components needed positive results well intensity transference gains daily life activitiestrial registrationwwwensaiosclinicosgovbrrbr467cv6 registered 10 october 2017 effects lower extremities constraint induced therapy gait balance function chronic hemipretic poststroke patients,1.0
theory mind neuroanatomical correlates people multiple sclerosis abstractbackground theory mind tom one several different concepts social cognition defined ability access mental states others adopt point view others although studies shown tom impaired people multiple sclerosis ms results based individual tom tasks conflicting studies shown deficits reading mind eyesnull test rmet others reported poor performance faux pas test fpt well rmet furthermore little known relationship tom performance neuroanatomical characteristics ms study investigated tom impairment relationship regional brain volume cortical thickness people msmethods crosssectional study included 20 participants relapseonset ms 27 age sexmatched volunteers healthy controls hc participants underwent neuropsychological np tests well tom tasks including rmet fpt participants ms underwent brain mri within 6 months undergoing np tom tests regional volume subcortical structures cortical thickness analysed based 3d t1weighted images using freesurfer softwareresults rmet fpt scores significantly lower participants ms hc p00049 p00071 respectively imaging analyses showed fpt scores rmet scores positively correlated right thalamus r2026 p0012 left pallidum r2039 p00021 volumes adjusting age furthermore surfacebased morphometry revealed significant correlation ageadjusted cortical thickness ten cortical areas including fusiform gyrus orbitofrontal cortex temporalparietal junction superior temporal gyrus fpt scoresconclusions study findings showed rmet fpt performances impaired participants ms furthermore fpt deficits rmet deficits significantly associated volume two subcortical structures well thickness ten cortical areas suggesting fpt appropriate task access tom performance ms,0.0
diagnostic dilemma hodgkins lymphoma versus tuberculosis acase report review theliterature background hodgkins lymphoma hl rare malignancy characterised histologically presence reedsternberg cells diagnosis lymphomas can difficult due broad nonspecific presentations disease can similar several conditions ranging infective inflammatory malignant causes one common differentials tuberculosis tb aim highlight diagnostic dilemma tb versus lymphoma atypical presentation hl explored areas research improvement nonsystematic literature review using medline database google scholar written consent obtained patient compliance ethical guidelinescase presentationa 23yearold asian female initially presented rheumatology oneyear history neuropathic pain alongside abnormal white cell count inflammatory markers investigated magnetic resonance imaging resulting incidental finding mediastinal mass pulmonary infiltrates initial diagnosis tb made despite testing negative acidfast bacilli antitubercular treatment commenced four months later following clinical deterioration investigations mediastinal biopsy assisted diagnosing stage iv hlconclusionslymphoma often misdiagnosed tb prolonging time treatment may adversely impact patient prognosis due disease progression existing tb guidelines smearnegative cases clear consider alternative diagnoses smearnegative tb lymphoma considered differential definitive diagnostic tests molecular testing histological examination biopsies considered earlier diagnostic workup prevent diagnostic delay,0.0
multiple sclerosis saudi arabia clinical social psychological aspects disease cureus 2021 jul 19 13 7 e16484 doi 107759 cureus16484 ecollection 2021 julabstractintroduction multiple sclerosis ms chronic autoimmune disorder affects central nervous system characterized demyelinating lesions disseminated space time depression common symptom ms pathogenesis multifactorial saudi arabia limited current literature incidence relationship depression ms study attempt meant address point prevalence depression risk factors relationship diseasemodifying therapy addition describe several clinical nutritional social aspects ms methods descriptive crosssectional study conducted jeddah saudi arabia target sample study consisted patients saudi arabia ms data collected included depression questionnaire based phq9 compliance therapy preferred therapy impact disease daily activity economic state results total 341 saudi ms patients enrolled present study gender distribution showed 654 n223 study population females mean age patients 34809907 years patients included study 956 depressive symptoms variant levels variable changes depression levels detected genders specifically moderate depression common males 33 females moderately severe depression 38 numbers relapses future vision changes workout associated statistically significant depression levels conclusion depressive symptoms common patients ms although diseasemodifying therapies available saudi arabia ms clinics multidisciplinary care yet efficiently activated nonpharmacological interventions smoking cessation exercise psychological health part management patient mspmid34430100 pmcpmc8372677 doi107759 cureus16484,1.0
defining prodromal phase multiple sclerosis based healthcare access portuguese population prodms study abstractbackgroundmultiple sclerosis ms chronic immunemediated disease central nervous system prodromal symptoms higher healthcare use suggested patients later develop msobjectivesassess healthcare utilization pattern relapsingremitting ms rrms patients five years prior ms diagnosismethodsretrospective multicentric study demographic clinical data drug prescriptions diagnostic tests collected electronic health records fiveyears previous ms diagnosis compared national dataresultsincluded 168 patients 112 667 female median age 3411 years mean number healthcare use per patient per year 3142 69 primary healthcare 47 frequent symptoms musculoskeletal 22 gastrointestinal 17 sensitive 14 sensory organs 14 median number diagnostic tests per patient 6 iqr 7 drug prescriptions per patient 6 iqr 9 frequently prescribed drugs analgesic antiinflammatories antibiotics anxiolytics high request rate mrisconclusionrrms patients high frequency healthcare utilization compared national data supports current evidence showing prodromal phase ms,1.0
escrtiii protein vps4 chmp4b chmp2b pathologically increased familial sporadic als neuronal nuclei abstractnuclear pore complex injury recently emerged early significant contributor familial sporadic als disease pathogenesis however molecular events leading pathological phenomenon characterized reduction specific nucleoporins neuronal nuclear pore complexes remain largely unknown due part lack knowledge regarding biological pathways proteins underlying nuclear pore complex homeostasis specifically human neurons recently uncovered aberrant nuclear accumulation escrtiii protein chmp7 initiates nuclear pore complex familial sporadic als neurons yeast nonneuronal mammalian cells nuclear relocalization chmp7 shown recruit escrtiii proteins chmp4b chmp2b vps4 facilitate nuclear pore complex nuclear envelope repair homeostasis using super resolution structured illumination microscopy find neither chmp4b chmp2b increased als neuronal nuclei contrast vps4 expression significantly increased als neuronal nuclei prior emergence nuclear pore injury chmp7 dependent manner however unlike prior chmp7 knockdown studies impaired vps4 function mitigate alterations npc integral transmembrane nucleoporin pom121 collectively data suggest alterations vps4 subcellular localization appear coincident nuclear pore complex injury therapeutic efforts mitigate pathogenic cascade targeted towards upstream events nuclear accumulation chmp7 previously described,0.0
rna doubleedged sword als pathogenesis front cell neurosci 2021 jul 19 15708181 doi 103389 fncel2021708181 ecollection 2021abstractamyotrophic lateral sclerosis als progressive fatal neurodegenerative disease affects upper lower motor neurons familial als accounts small subset cases 1015 caused dominant mutations one 10 known genes multiple genes causally pathologically linked als frontotemporal dementia ftd many genes encode rnabinding proteins role dysregulated rna metabolism neurodegeneration actively investigated addition defects rna metabolism recent studies provide emerging evidence rna can contribute degeneration motor cortical neurons review discuss roles altered rna metabolism rnamediated toxicity context tardbp fus c9orf72 mutations specifically focus recent studies describe toxic rna potential initiator disease diseaseassociated defects specific rna metabolism pathways well rnabased approaches can used potential therapies altogether highlight importance rnabased investigations molecular progression als well need rnadependent structural studies diseaselinked rnabinding proteins identify clear therapeutic targetspmid34349625 pmcpmc8326408 doi103389 fncel2021708181,0.0
role macrophage polarization associated mechanisms regulating antiinflammatory action acupuncture literature review perspectives abstractacupuncture used treatment variety inflammatory conditions diseases however mechanisms antiinflammatory action complex systematically investigated macrophages key components innate immune system thus balancing m1 m2 macrophage ratio modulating cytokine levels inflammatory environment may desirable therapeutic goals evidence shown acupuncture antiinflammatory actions affect multiple body systems including immune locomotory endocrine nervous digestive respiratory systems downregulating proinflammatory m1 upregulating antiinflammatory m2 macrophages well modulating associated cytokine secretion macrophage polarization controlled interlocking pathways extrinsic factors local tissue microenvironment neuralendocrineimmune systems suggested polarization t lymphocytes cytokine secretions resulting modulation autonomic nervous system hypothalamicpituitaryadrenal axis may upstream mechanisms acupunctureinduced macrophage polarization propose macrophage polarization principal pathway involved acupuncture immune regulation provide scientific basis clinical application acupuncture inflammatory conditions,0.0
arm ergometry improve mobility progressive multiple sclerosis ambos results pilot randomized controlled trial front neurol 2021 jul 19 12644533 doi 103389 fneur2021644533 ecollection 2021abstractbackground walking disability one frequent burdening symptoms progressive multiple sclerosis ms exercise intervention studies showed improvement mobility performance conducted low moderately disabled relapsingremitting ms patients interventions using legs however ms patients substantial walking disability hardly can perform tasks earlier work indicated aerobic arm training might also improve walking performance therefore therapeutic option already moderately disabled progressive ms patients methods patients progressive ms edss 465 randomized using computergenerated algorithm list either waitlist control group cg intervention group ig ig performed 12week homebased individualized arm ergometry exercise training program maximum walking distance measured 6min walking test 6mwt primary endpoint secondary endpoints included aerobic fitness mobility tests cognitive functioning well fatigue depression results n 86 screened patients 53 moderate disability mean edss 55 sd 09 included data 39 patients analyzed patients ig showed strong adherence program mean 67 sd 264 training sessions maximum work load p max increased training group fitness indicators walking distance 6mwt improved training waitlist group significantly trained patients similarly mobility measures showed differential group effect cognitive functioning remained unchanged serious events attributable intervention occurred conclusion although maximum work load improved 3 months highfrequency arm ergometry training low moderate intensity show improved walking ability cognitive functioning progressive ms compared waitlist cg study registered wwwclinicaltrialsgov nct03147105 funded local ms selfhelp organizationpmid34349716 pmcpmc8326796 doi103389 fneur2021644533,0.0
pharmacological inhibition pi3k pten akt mtor signalling pathways limits follicle activation induced ovarian cryopreservation vitro culture background cryopreservation transplantation ovarian tissue otctp represent promising fertility preservation technique prepubertal patients patients requiring urgent oncological management however major obstacle technique follicle loss due among others accelerated recruitment primordial follicles transplantation process leading follicular reserve loss graft thereby potentially reducing lifespan study aimed assess cryopreservation impacts follicle activationresultswestern blot analysis pi3k pten akt mtor signalling pathways showed activated mature juvenile slowfrozen murine ovaries compared control fresh ovaries use pharmacological inhibitors follicle signalling pathways cryopreservation process decreased cryopreservationinduced follicle recruitment second aim study use vitro organotypic culture cryopreserved ovaries test pharmacological inhibitors pi3k pten akt mtor pathways vitro organotypic cultureinduced activation pi3k pten akt pathway counteracted cryopreservation rapamycin vitro culture presence ly294002 results confirmed follicle density quantifications indeed follicle development affected vitro organotypic culture pi3k pten akt mtor pharmacological inhibitors preserve primordial follicle reserveconclusionsour findings support hypothesis inhibitors mtor pi3k might attractive tool delay primordial follicle activation induced cryopreservation culture thus preserving ovarian reserve retaining follicles functionally integrated state,0.0
migrainelike positive visual phenomena related focal cortical lesions undetectable visual field defects case rep ophthalmol 2021 jul 19 12 2 653658 doi 101159 000517792 ecollection 2021 mayaugabstractmigraines commonly associated visual aura characteristic clinical presentation cortical lesions within close proximity retrochiasmal visual pathways may also present manner mimics migrainous visual phenomena cases may small manifest visual field defect formal testing present 4 patients 3 females 1 male average age 485 range 2867 years migrainelike visual disturbances related right temporal meningioma occipital cavernoma occipital lobe infarction demyelination optic radiations presenting sign multiple sclerosis patient underwent neurosurgical intervention 1 patient occipital lobe infarct complete resolution symptom initial presentation patients normal visual fields followup thinning evident optical coherence tomography cases emphasize importance history assessing patients transient positive visual phenomena identify pathology may present without visual field defects clinical features raise doubt diagnosis migraine visual aura include absence headache brief visual disturbance lasting 5 min lasting 60 min age 40 especially past medical history migrainepmid34413757 pmcpmc8339477 doi101159 000517792,1.0
involvement lactosylceramide central nervous system inflammation related neurodegenerative disease front aging neurosci 2021 jul 19 13691230 doi 103389 fnagi2021691230 ecollection 2021abstractneurodegenerative diseases class slowprogressing terminal illnesses characterized neuronal lesions multiple sclerosis ms alzheimers disease ad parkinsons disease pd amyotrophic lateral sclerosis als incidence increases age associated burden families society will become increasingly prominent aging general population recent years growing studies shown lactosylceramide laccer plays crucial role progression neurodegeneration although diseases different pathogenic mechanisms etiological characteristics based latest research progress study expounds pathogenic role laccer driving central nervous system cns inflammation well role membrane microstructure domain lipid rafts metabolite gangliosides discusses detail links pathogenesis neurodegenerative diseases view providing new strategies ideas study pathological mechanisms drug development neurodegenerative diseases futurepmid34349634 pmcpmc8326838 doi103389 fnagi2021691230,0.0
interpretable deep learning means decrypting disease signature multiple sclerosis j neural eng 2021 jun 28 doi 101088 17412552 ac0f4b online ahead printabstractobjective mechanisms driving multiple sclerosis ms still largely unknown calling new methods allowing detect characterize tissue degeneration since early stages disease aim decrypt microstructural signatures primary progressive versus relapsingremitting state disease based diffusion structural mri dataapproach selection microstructural descriptors based 3dshore simple harmonics oscillator based reconstruction estimation set new algebraically independent rotation invariant spherical harmonics features rif considered used feed convolutional neural networks cnns models classical measures derived diffusion tensor imaging dti fractional anisotropy fa mean diffusivity md used benchmark diffusion mri dmri finally t1weighted t1w images also considered sake comparison stateoftheart cnn model fit feature map layerwise relevance propagation lrp heatmaps generated model target class subject test set average heatmaps calculated across correctly classified patients sizecorrected metrics derived set regions interest rois assess lrp contrast two classesmain results results demonstrated dmri features extracted grey matter gm tissues can help disambiguating ppms rrms patients moreover lrp heatmaps highlight areas high relevance relate well known literature ms diseasesignificance within patient stratification task lrp allows detecting input voxels mostly contribute classification patients either two classes feature potentially bringing light hidden data properties might reveal peculiar diseasestate factorspmid34181581 doi101088 17412552 ac0f4b,0.0
phlebosclerotic colitis nonasian patient case report background phlebosclerotic colitis rare condition high mortality seen almost exclusively asian patients 60 years old slight male predominance although predominantly affects right colon seems related cases using natural herbal medicines neither etiology pathogenesis knowncase presentationwe present extremely rare case 62yearold spanish white man patient nonasian ethnicity history using natural medications diagnosed phlebosclerotic colitis submucosal veinsconclusionto date case reported spain second reported europe literature due nonspecific symptoms insidious radiological findings disease early mild stages well exclusive submucosal involvement presented necessary treating physician high level suspicion diagnosis,0.0
outcomes covid19 infection multiple sclerosis related conditions oneyear pandemic experience multicenter new york covid19 neuroimmunology consortium nycnic abstractobjectiveto determine outcomes covid19 patients multiple sclerosis ms related conditions determine predictors outcomesmethodsthis multicenter observational cohort study patients ms related cns autoimmune disorders developed confirmed highly suspected covid19 infection 2 1 2020 12 31 2020main outcome measurethe primary outcome measure hospitalization status due covid19 severity infection measured using 4point ordinal scale 1 home care 2 hospitalization without mechanical ventilation 3 hospitalization mechanical ventilation 4 deathresultsof 474 patients study 633 confirmed covid19 infection 939 diagnosed ms phenotype mean age 4513 meansd years 72 female 86 treated dmt time infection 58 patients 122 hospitalized 24 patients 51 critically ill requiring icu care outcome death 15 patients 32 died higher neurological disability older age independently predicted hospitalization 85 102 120 patients known antibody results treated anticd20 therapies seropositive 395 17 43 patients treated anticd20 demonstrated seropositivity p00001 25 2 8 patients pcrconfirmed covid19 treated anticd20 therapies demonstrated seropositivityconclusionsneurological disability older age independently predicted hospitalization due covid19 additionally results demonstrate anticd20 therapies significantly blunt humoral responses postinfection finding carries implications regards natural vaccinemediated immunity,0.0
covid19 vaccines multiple sclerosis diseasemodifying therapies much evidence emerged since first editorial april 2020 use multiple sclerosis ms diseasemodifying therapies dmts pandemic giovannoni et al 2020 publication msards baker colleagues biology underpinning interaction dmts sarscov2 baker et al 2020 now clear apart anticd20 therapies rituximab ocrelizumab ms dmts appear increase risk covid19 severe covid19 sormani et al 2021 peeters et al 2020 salter et al 2021 importantly people ms pwms treated interferonbeta less likely get severe covid19 sormani et al 2021 presumably due antiviral effects monk et al 2021 risks covid19 associated anticd20 therapy relatively small approximate doubling liability compared people dmts sormani et al 2021 peeters et al 2020 important drivers severe covid19 death age disability presence comorbidities sormani et al 2021 louapre et al 2020 male sex social determinants health deprivation ethnicity also play important role outcomes covid19 bhaskaran et al 2021 counselling individual patients doubling risk getting severe covid19 anticd20 therapy stressed doubling low risk particularly low absolute risk remains still low absolute risk people ms use one online risk calculators example online qcovid risk calculator developed university oxford https qcovidorg assess personal risk hopefully approach final wave covid19 pandemic countries anticipate herd immunity towards end summer northern hemisphere question vaccine readiness relation dmts baker et al 2020 reyes et al 2021 vaccine hesitancy concerning longterm safety covid19 vaccines remain topical reyes et al 2021 xiang et al 2021 moniz dionsio et al 2021 recent publication israel shows blunted antibody response pfizerbiontech mrnacovid19 vaccine ocrelizumab fingolimod treated patients compared treated cladribine dmt achiron et al 2021 suboptimal ocrelizumab fingolimod vaccine response results substantiated small french study bigaut et al 2021 part refuted italian reallife study examined 32 patients ms 10 16 625 patients managed fingolimod 6 16 375 treated ocrelizumab positive serological response vaccination s et al 2021 suspect discrepancy may relate sensitivity assay used detect antisarscov2 spike protein antibodies results surprising good evidence anticd20 therapies cioc et al 2008 fingolimod han et al 2004 s1p modulator disrupt germinal centre gc functioning lymphoid tissue naive bcells educated help follicular thelper cells gcs antibody gene rearrangement results class switching example igm one igg subtypes followed affinity maturation selection highaffinity bcell receptors membranebound antibodies prior formation memory bcells plasmablast clones exit gcs produce highaffinity soluble igg can detected peripheral blood lu craft 2021 important stress vaccine immunity antibody responses bcell mediated tcell responses also important teijaro farber 2021 swiss study yet peerreviewed evaluated 96 anticd20 treated patients 29 immunocompetent controls antispike sarscov2 igg antibodies detected 49 patients second mrnacovid19 vaccine dose compared 100 controls sarscov2 specific interferon release tcell assay detected 17 patients 86 healthy controls moor et al 2021 5 patients 86 healthy controls showed positive results antibody b cell t cell assays importantly time elapsed since last dose anticd20 therapy 76 months peripheral blood bcell reconstitution cd19+ cells 27 l cd4+ lymphocyte count 653 l predicted antibody vaccine response moor et al 2021 contrast us group investigators confirmed anticd20 therapy significantly reduced antisarscov2 spike receptorbinding domain rbd specific antibody memory b cell responses patients also demonstrated effect reduced longer duration last infusion anticd20 treatment extent b cell reconstitution apostolidis et al 2021 contrast patients treated anticd20 therapies generated antigenspecific cd4+ cd8+ tcell responses following vaccination mrna vaccines apostolidis et al 2021 group patients anticd20 therapy tended skew immune response away socalled tfollicular helper cells augmented induction antigenspecific cd8+ t cells apostolidis et al 2021 conflicting results probably due methodological issues generally agreed reasonable igg antibody response vaccine indicates good cd4+ t cell response particularly tfollicular helper cell reaction required help educate produce antigenspecific memory bcells plasmablasts gcs lu craft 2021 swiss study 49 anticd20 treated patients made antibody response compared 17 interferon tcell assay suggests problem sensitivity tcell assay moor et al 2021 important note majority patients ms anticd20 therapy s1pmodulator make unremarkable recovery covid19 implies innate tcell responses critical clearing sarscov2 functional comparison bcell antibody responses vital eliminating primary infection sormani et al 2021 hughes et al 2021 likely play important role secondary immune responses particularly sterilizing immunity ie preventing repeat infection people infected past infection vaccination sette crotty 2021 putting context seems highly likely patients ms placed anticd20 therapy s1pmodulator will blunted necessarily absent antibody responses covid19 vaccines patients likely benefit protective least partially protective tcell responses vaccine keeping happens experience naturally occuring sarscov2 infection immunity unlikely sterilizing particularly new emerging sarscov2 varieties eg delta variant partially immune escape strains despite immunity may sufficient prevent symptomatic infection severe disease death covid19 message therefore remain patients anticd20 therapy s1p modulator fingolimod siponimod ozanimod ponesimod receive one licensed covid19 vaccines soon possible principle pandemic immunity particularly tcell immunity better immunity point pandemic recommend withdrawal anticd20 s1p modulator therapy optimise vaccine responses risk rebound disease activity stopping washing s1p modulator particularly hazardous barry et al 2019 conversely longer duration action anticd20 therapies makes rebound disease activity withdrawal less issue baker et al 2020 despite know whether necessary needed level bcell reconstitution required optimise vaccine responses anticipate studies highlighted pedotti colleagues pedotti et al 2021 journal will find pwms therapies vaccinated covid19 albeit suboptimally immunological perspective enough immunity prevent covid19 shape form like conclude addressing recommendation people ms seasonal influenza vaccines 5year pneumococcal vaccines travel vaccines required perhaps seasonal booster covid19 vaccine point people ms anticd20 s1p modulators potentially emerging ms dmts bruton tyrosine kinase btk inhibitors must accept immunocompromised immunosuppression extends blunted necessarily absent vaccine responses well accumulation global data will learn optimization vaccine responses may achieved without compromising effective management ms vital mstreating clinicians balance small absolute risks suffering severe covid19 potentially death blunted vaccine responses anticd20 therapies blunted vaccine responses s1p modulators risks undertreating treating ms,0.0
chondromalacia patellae current options emerging cell therapies abstractchondromalacia patellae cmp also known runners knee typically occurs young patients characterized anterior knee pain akp associated visible changes patellar cartilage initial pathological changes include cartilage softening swelling edema cmp caused several factors including trauma increased cartilage vulnerability patellofemoral instability bony anatomic variations abnormal patellar kinematics occupation hazards cmp may reversible may progress develop patellofemoral osteoarthritis quadriceps wasting patellofemoral crepitus effusion obvious clinical indications additionally radiological examinations also necessary diagnosis magnetic resonance imaging mri noninvasive diagnostic method holds promise unique ability potentially identify cartilage lesions modalities conventionally proposed treat cartilage lesions pf joint none emerged gold standard neither alleviated symptoms function prevent oa degeneration recently researchers focused cartilagetargeted therapy various efforts including cell therapy tissue emerge cartilage regeneration exhibit promising regime especially application mesenchymal stem cells mscs intraarticular injections variously sourced msc found safe beneficial treating cmp improved clinical parameters less invasiveness symptomatic relief reduced inflammation mechanism msc injection remains clinical investigation tremendously promising cmp treatment short review etiology mri diagnosis treatment cmp especially treatment cellbased therapies reviewed,0.0
primary cutaneous cryptococcosis patient fingolimod case report cureus 2021 jul 17 13 7 e16444 doi 107759 cureus16444 ecollection 2021 julabstractprimary cutaneous cryptococcosis uncommon condition patients immunosuppression older age susceptible infection warranting investigations underlying systemic disease report case 49yearold male multiple sclerosis remission fingolimod presented nonhealing skin lesion upper thigh duration two years skin biopsy showed dermal parasitized histiocytes serum antigens histoplasmosis cryptococcus negative investigation polymerase chain reaction pcr demonstrated cutaneous cryptococcal infection associated systemic signs symptoms case report highlights uncommon presentation cutaneous cryptococcosis unexposed skin surface successful rapid improvement following fluconazole therapy without fingolimod discontinuationpmid34422475 pmcpmc8367091 doi107759 cureus16444,0.0
review treatment options epilepsy tuberous sclerosis complex towards precision medicine ther adv neurol disord 2021 jul 17 1417562864211031100 doi 101177 17562864211031100 ecollection 2021abstracttuberous sclerosis complex tsc rare genetic disorder caused mutations tsc1 tsc2 genes encode proteins antagonise mammalian isoform target rapamycin complex 1 mtorc1 key mediator cell growth metabolism tsc characterised development benign tumours multiple organs together neurological manifestations including epilepsy tscassociated neuropsychiatric disorders tand epilepsy occurs frequently associated significant morbidity mortality however management challenging due intractable nature seizures preventative epilepsy treatment key aim especially patients epilepsy may higher risk developing severe cognitive behavioural impairment vigabatrin given preventatively reduces risk severity epilepsy although benefits tand inconclusive promising results pave way evaluating treatments preventative capacity especially may address underlying pathophysiology tsc including everolimus cannabidiol ketogenic diet kd everolimus mtor inhibitor approved adjunctive treatment refractory tscassociated seizures demonstrated significant reductions seizure frequency compared placebo improvements sustained 2 years treatment highly purified cannabidiol recently approved us epidiolex tscassociated seizures patients 1 years age kd may also participate regulation mtor pathway review focusses pivotal clinical evidence surrounding potential targeted therapies may form foundation precision medicine tscassociated epilepsy well current treatments including antiseizure drugs vagus nerve stimulation surgery new future therapies also discussed together potential preventative treatment targeted therapies due advances understanding molecular genetics pathophysiology tsc represents prototypic clinical syndrome studying epileptogenesis impact precision medicinepmid34349839 pmcpmc8290505 doi101177 17562864211031100,0.0
tripartite knowledge translation program innovative patientcentered approach clinical research participation individuals multiple sclerosis mult scler int 2021 jul 16 20215531693 doi 101155 2021 5531693 ecollection 2021abstractbackground knowledge translation kt models represent individuals perspective sign effective kt common challenges kt include participant engagement organization team time demands participants implemented unique tripartite kt program 1 share current research 2 inform persons living multiple sclerosis pwms clinical research process 3 invite pwms immediately participate clinical research primary aim determine participants perspectives value acceptability experiential research program offered patient family educational conferencemethods team researchers identified factors impact logistics hosting experiential research program conference designed unique tripartite kt program local multiple sclerosis ms society engaged select appropriate location invite stakeholders conference survey determine participants perspectives value acceptability experiential research program developed analyzedresults 65 pwms attended conference 44 677 participated onsite experiential research program 727 participants completed survey 938 stated strongly agree agree following statements feel like participating research today valuable experience feel like contributing ms research 100 participants agreed strongly agreed asked like see research activities taking place kinds eventsconclusions paper describes logistics challenges conducting experiential kt program proved rewarding pwms majority pwms attending conference agreed participate onsite experiential research program overwhelming majority participants felt experience valuablepmid34327022 pmcpmc8310439 doi101155 2021 5531693,0.0
catalog validity indices step counting wearable technologies treadmill walking cadencekids study background wearable technologies play important role measuring physical activity pa promoting health standardized validation indices ie accuracy bias precision compare performance step counting wearable technologies young peoplepurposeto produce catalog validity indices step counting wearable technologies assessed different treadmill speeds slow 0832 km h normal 4064 km h fast 7280 km h wear locations waist wrist arm thigh ankle age groups children 612 years adolescents 1317 years young adults 1820 years methodsone hundred seventeen individuals 131 42 years 504 female participated crosssectional study completed 5min treadmill bouts 08 km h 80 km h wearing eight devices waist actical actigraph gt3x+ nl1000 sw200 wrist actigraph gt3x+ arm sensewear thigh activpal ankle stepwatch directly observed steps served criterion measure accuracy mean absolute percentage error mape bias mean percentage error mpe precision correlation coefficient r standard deviation sd coefficient variation cov computedresultsfive eight tested wearable technologies ie actical waistworn actigraph gt3x+ activpal stepwatch sw200 performed 5 mape range normal speeds generally waist mape 4 thigh 4 ankle 5 locations displayed higher accuracy wrist location 23 normal speeds average wearable technologies displayed lowest accuracy across slow speeds mape 501 355 highest accuracy across normal speeds mape 159 217 speed wear location significant effect accuracy bias p 0001 precision p 005 age effect p 005 conclusionsstandardized validation indices focused accuracy bias precision cataloged speed wear location age group serve important reference points selecting evaluating device performance young people moving forward reduced performance can expected slow walking speeds 08 32 km h devices ankleworn thighworn devices demonstrated highest accuracy speed wear location significant effect accuracy bias precisiontrial registrationclinicaltrialsgovnct01989104 registered november 14 2013,0.0
longitudinal observational analysis neuronal injury biomarkers case report patient paraneoplastic anticrmp5 antibodyassociated transverse myelitis front neurol 2021 jul 16 12691509 doi 103389 fneur2021691509 ecollection 2021abstractbiomarkers needed guide therapeutic decision making autoimmune paraneoplastic neurologic disorders describe case paraneoplastic collapsing responsemediator protein5 crmp5 associated transverse myelitis tm plasma neurofilament light nfl chain glial fibrillary protein gfap levels observed 14month clinical course correlating radiographical clinical outcome measures response treatment blood csf samples obtained diagnosis well 7 14 months treatment time initial diagnosis plasma nfl 78262 pg ml gfap 28326 pg ml significantly elevated initial treatment iv steroids plasma exchange plex followed neuroendocrine tumor removal chemotherapy radiation initial improvement chemotherapy patient experienced clinical worsening transient elevation plasma nfl 10327 pg ml gfap 21158 pg ml levels whole body positron emission tomography pet scan demonstrate recurrence malignancy repeat plex rituximab induction resulted improvements patient function neurologic exam plasma biomarker levels knowledge first described longitudinal prospective analysis neuronal injury biomarkers association clinical treatment outcomes crmp5 myelitis findings suggest clinical improvement correlates nfl gfap concentrationspmid34349723 pmcpmc8328144 doi103389 fneur2021691509,0.0
adherence therapy physical mental quality life patients multiple sclerosis j pers med 2021 jul 16 11 7 672 doi 103390 jpm11070672abstractensuring multiple sclerosis ms patients adherence therapy often challenging crucial survival healthrelated quality life hrqol aim present study outline connections adherence physical mental hrqol levels psychological readiness engage treatment levels social support anthropometric sociodemographic clinical factors patients suffering ms crosssectional study involved sample 237 italian ms patients survey conducted structured selfadministered online questionnaire using validated measures quality life adherence therapy anthropometric sociodemographic psychological clinical variables path analysis used test overall structure associations variables pathway indicates positive association mental health index stronger degree engagement longterm relationship physical health index positively associated age occupation specific form ms relapses previous year raised odds better adherence therapy increase body mass index bmi reduced findings help management ms patients promoting behavioral interventions take psychological sociodemographic peculiarities patient account view improving adherence therapypmid34357139 doi103390 jpm11070672,0.0
predicting conversion multiple sclerosis patients radiologically isolated syndrome retrospective study ther adv neurol disord 2021 jul 16 1417562864211030664 doi 101177 17562864211030664 ecollection 2021abstractaims retrospectively analyse bernese radiologically isolated syndrome ris cohort goal developing prediction score conversion multiple sclerosis ms methods total 31 patients ris identified screening medical records neurological patients seen university hospital bern 2004 2017 diagnoses radiologically isolated syndrome ris adhering 2009 okuda recommendations analysed clinical paraclinical magnetic resonance imaging data maximum followup period 3 years identified significant predictors conversion msresults data available 31 patients meeting 2009 okuda ris criteria 3 years follow 5 31 ris patients converted relapsingremitting rr ms univariate analysis gadolinium gd enhancement brainstem cerebellar hemisphere lesions immune cell count albumin concentration cerebrospinal fluid csf antinuclear antibody ana positivity serum identified significant predictors conversion ms integrating factors risms prediction score enabled us calculate cutoff prediction conversion ms within 3 years high specificity 10 95 confidence interval ci 084100 acceptable sensitivity 06 95 ci 017093 conclusion risms prediction score validated independent cohort integrating radiological gd enhancement brainstem cerebellar hemisphere lesions paraclinical factors ana serum cell count albumin csf useful prognostic tool early recognition ris patients high risk clinical progression mspmid34349838 pmcpmc8287642 doi101177 17562864211030664,0.0
s1p2g12 signaling inhibits astrocytic glutamate uptake mitochondrial oxygen consumption eneuro 2021 apr 23eneuro0040212021 doi 101523 eneuro0040212021 online ahead printabstractglutamate principal excitatory neurotransmitter human brain following neurotransmission astrocytes remove excess extracellular glutamate prevent neurotoxicity glutamate neurotoxicity reported multiple neurological diseases including multiple sclerosis ms representing shared neurodegenerative mechanism potential modulator glutamate neurotoxicity bioactive lysophospholipid sphingosine 1phosphate s1p signals five cognate g proteincoupled receptors gpcrs s1p1 s1p5 however clear link glutamate homeostasis s1p signaling established s1p receptor knockout mice primary astrocyte cultures receptorselective chemical tools used examine effects s1p glutamate uptake s1p inhibited astrocytic glutamate uptake dosedependent manner increased mitochondrial oxygen consumption primarily s1p2 primary cultures wildtype mouse astrocytes expressed s1p1 2 3 transcripts selective deletion s1p1 s1p3 cerebral cortical astrocytes alter s1pmediated dosedependent inhibition glutamate uptake pharmacological antagonists s1p2null astrocytes g12 hemizygousnull astrocytes indicated s1p2g12rho rock signaling primarily responsible s1pdependent inhibition glutamate uptake addition s1p exposure increased mitochondrial oxygen consumption rates ocrs wildtype astrocytes reduced ocrs s1p2null astrocytes implicating receptor selective metabolic consequences s1pmediated glutamate uptake inhibition astrocytic s1ps1p2 signaling increased extracellular glutamate contribute neurotoxicity effect observed fdaapproved s1p receptor modulators siponimod fingolimod development use s1p2selective antagonists may provide new approach reduce glutamate neurotoxicity neurological diseasessignificance statementextracellular glutamate excitotoxic levels controlled astrocyte uptake sphingosine 1phosphate s1p bioactive lipid originating cell membrane sphingolipids associates carrier molecules like albumin apom apoa4 produce cellular effects s1p signals extracellularly five gpcrs found higher concentrations neurological diseases like multiple sclerosis excitotoxic neurodegeneration implicated show astrocytic s1p2 activation s1p results glutamate uptake inhibition promote excitotoxic damage s1p receptor modulators including approved drugs treating multiple sclerosis eg fingolimod fty720 siponimod baf312 engage s1p2 thus avoiding glutamate uptake inhibition s1p2 antagonists may provide means reduce s1pinduced glutamate neurotoxicity ameliorate neurological diseasespmid33893167 doi101523 eneuro0040212021,0.0
key points keep mind related covid19 vaccines people multiple sclerosis abstractvaccinations often effective tool certain diseases known mankind interaction multiple sclerosis ms discussed decades rapidly accumulating numbers cases deaths due covid19 global effort respond pandemic terms scale speed different platforms currently used around world development best covid19 vaccine covid19 vaccines already approved different regulatory agencies scarce data large cohorts regarding efficacy security covid19 vaccines people ms short review aimed important information keep mind regarding topic,0.0
prediction combination therapies based topological modeling immune signaling network multiple sclerosis background multiple sclerosis ms major health problem leading significant disability patient suffering although chronic activation immune system hallmark disease pathogenesis poorly understood current treatments ameliorate disease may produce severe side effectsmethodshere applied networkbased modeling approach based phosphoproteomic data uncover differential activation signaling wiring healthy donors untreated patients different treatments based patientspecific networks aimed create new approach identify drug combinations revert signaling healthylike state performed ex vivo multiplexed phosphoproteomic assays upon perturbations multiple drugs ligands primary immune cells 169 subjects ms patients n129 matched healthy controls n40 patients either untreated treated fingolimod natalizumab interferon glatiramer acetate experimental therapy epigallocatechin gallate egcg generated donor dynamic logic model fitting bespoke literaturederived network msrelated pathways perturbation data last developed approach based network topology identify deregulated interactions whose activity reverted healthylike status combination therapy experimental autoimmune encephalomyelitis eae mouse model ms used validate prediction combination therapiesresultsanalysis models uncovered features healthy disease drugspecific signaling networks predicted several combinations approved ms drugs revert signaling healthylike state specifically tgf activated kinase 1 tak1 kinase involved transforming growth factor 1 proprotein tgf tolllike receptor b cell receptor response inflammation pathways found highly deregulated codruggable ms drugs studied one predicted combinations fingolimod tak1 inhibitor validated animal model msconclusionsour approach based donorspecific signaling networks enables prediction targets combination therapy ms complex diseases,0.0
nacetyl cysteine administration affects cerebral blood flow measured arterial spin labeling mri patients multiple sclerosis heliyon 2021 jul 16 7 7 e07615 doi 101016 jheliyon2021e07615 ecollection 2021 julabstractbackground purpose study explore administration nacetylcysteine nac patients multiple sclerosis ms resulted altered cerebral blood flow cbf based arterial spin labeling asl magnetic resonance imaging mri methods twentythree patients mild moderate ms 17 relapsing remitting 6 primary progressive randomized either nac plus standard care n 11 standard care n 12 experimental group received nac intravenously 50 mg kg per week orally 500mg 2x day six days patients groups evaluated initially 2 months receiving nac waitlist control asl mri measure cbf clinical symptom questionnaires also completed time pointsresults cbf data showed significant differences several brain regions including pons midbrain left temporal frontal lobe left thalamus right middle frontal lobe right temporal hippocampus p 0001 ms group treatment nac compared control group selfreported scores related cognition attention also significantly improved nac group compared control groupconclusions results study suggest nac administration alters resting cbf ms patients associated qualitative improvements cognition attention given findings large scale efficacy studies will value determine potential clinical impact nac course illness patients ms well effective dosages differential effects across subpopulationspmid34377857 pmcpmc8327674 doi101016 jheliyon2021e07615,0.0
mesenchymal stem cells ameliorate renal fibrosis galectin3 akt gsk3 snail signaling pathway adenineinduced nephropathy rat background tubulointerstitial fibrosis tif one main pathological features various progressive renal damages chronic kidney diseases mesenchymal stromal cells mscs verified significant improvement therapy fibrosis diseases mechanism still unclear attempted explore new mechanism therapeutic target mscs renal fibrosis based renal proteomicsmethodstif model induced adenine gavage bone marrowderived mscs injected tail vein modeling renal function fibrosis related parameters assessed masson sirius red immunohistochemistry western blot renal proteomics analyzed using itraqbased mass spectrometry possible mechanism explored transfected galectin3 gene knockdown gal3 kd overexpression gal3 oe hk2 cells lentiviral vectorresultsmscs treatment clearly decreased expression sma collagen type ii iii tgf1 kim1 psmad2 3 il6 il1 tnf compared model rats p38 mapk increased proteomics showed 40 proteins exhibited significant differences 30 upregulated 10 downregulated compared mscs group model group galectin3 downregulated significantly renal tissues tgf1induced rat tubular epithelial cells interstitial fibroblasts consistent itraq results gal3 kd notably inhibited expression pakt pgsk3 snail tgf1induced hk2 cells fibrosis contrary gal3 oe obviously increased expression pakt pgsk3 snailconclusionthe mechanism mscs antirenal fibrosis probably mediated galectin3 akt gsk3 snail signaling pathway galectin3 may valuable target treating renal fibrosis,0.0
immunemediated inflammatory diseases nutrition results online survey patients practices perceptions background central role microbiota contribution diet immunemediated inflammatory diseases imid increasingly examined however patients perspectives nutrition impact disease received lot attention aimed directly collect information patients imid dietary behaviors perceptions influence nutrition diseasemethodsadult patients rheumatoid arthritis ankylosing spondylitis psoriatic arthritis crohns disease ulcerative colitis psoriasis registered online patient community invited participate study complete online selfadministered questionnaire assessed patients dietary knowledge choices collecting information diet regimens following recommended perceptions diet consequences diseaseresultsfifty patients per target disease included mean age 481 years 95ci 467496 sociodemographic clinical characteristics varied across diseases since diagnosis 44 patients changed eating habits mainly patients inflammatory bowel disease 69 making change initiative patients change diet habits reported received nutritional advice healthcare professionals hcp 69 cases perceived impact nutrition symptoms mixed overall 74 patients reported positive consequences 60 negative ones varied across diseases patients psoriasis experienced positive consequences changing diet reduction stress improved mental health patients crohns disease reported negative effects increased fatigue disturbed sleep patients rheumatic diseases ulcerative colitis reported weight loss better physical fitness also increased fatigueconclusionseven differences exist across diseases importance nutrition potential positive role symptom management acknowledged majority patients however need demand patients receive dietary advice developing therapeutic education tools nutrition people imid involving patients organizations provide useful information encourage communication hcp patients,0.0
screening reveals sterol derivatives prodifferentiation prosurvival potent cytotoxic effects oligodendrocyte progenitor cells acs chem biol 2021 jul 7 doi 101021 acschembio1c00461 online ahead printabstractinducing formation new oligodendrocytes oligodendrocyte progenitor cells opcs represents potential approach repairing loss myelin observed multiple sclerosis diseases recently demonstrated accumulation specific cholesterol precursors 8 9unsaturated sterols dominant mechanism dozens small molecules enhance oligodendrocyte formation evaluated library 56 sterols steroids evaluate whether classes bioactive sterol derivatives may also influence mouse oligodendrocyte precursor cell opc differentiation survival library identified u73343 potent enhancer oligodendrocyte formation induces 8 9unsaturated sterol accumulation inhibition cholesterol biosynthesis enzyme sterol 14reductase contrast found mouse opcs remarkably vulnerable treatment glycosterol osw1 oxysterolbinding protein osbp modulator induces golgi stress opc death low picomolar range subsequent smallmolecule suppressor screen identified mtor signaling key effector pathway mediating osw1s cytotoxic effects mouse opcs finally evaluation panel er golgi stressinducing small molecules revealed mouse opcs highly sensitive perturbations closely related neural progenitor cells together studies highlight wideranging influence sterols steroids opc cell fate 8 9unsaturated sterols positively enhancing differentiation oligodendrocytes osw1 able induce lethal golgi stress remarkable potencypmid34232635 doi101021 acschembio1c00461,1.0
dignity patients palliative needs middle east integrative review background patients palliative needs experience high psychological symptom distress may lead hopelessness impaired sense dignity maintaining patient dignity quality valued core aim palliative care notion dignity often explained functionality symptom relief autonomy decision making however understanding implications middle eastern countries clearthe aim review 1 explore understanding dignity dignity preserved adult patients palliative care needs middle east 2 critically assess findings dignity model dominant western literaturemethodusing integrative review searched four databases embase psychinfo cinahl pubmed databases retrieve broad literature palliative care often chosen palliative care reviews enhance search strategy three online journals hand searched reference lists review papers scanned forward citations sought time limits applied retrieved papers assessed independently two authors including quality assessment using hawkers appraisal toolresultsout 5113 studies retrieved 294 full texts assessed sixteen studies included synthesis fourteen published iran seven themes developed data analysis maintaining privacy secrecy gentle communication dialogue preserves hope instead blunt truthtelling abundance characterised accessibility medical supplies financial stability family support relatives deliver major assistance care physical fitness reliable health care social justice endorses equal care allconclusionthe results compatible existing evidence dignity model ascertaining dignity socially mediated influenced interactions physical fitness nevertheless findings highlight patient dignity also shaped sociopolitical cultural economic conditions country family support gentle communication accessible health care essential elements,0.0
risk depression multiple sclerosis across diseasemodifying therapies abstractbackgrounddepression use antidepressants common among patients multiple sclerosis ms compared general population relation psychiatric comorbidity use different diseasemodifying therapies dmts less clearobjectiveto determine whether risk incident depression antidepressant use differed across dmts assess whether depression antidepressants affected risk dmt discontinuation ms relapsesmethodswe prospectively followed 8years registerbased nationwide cohort 3803 relapsingremitting ms patientsresultspatients rituximab lower risk diagnosed depression initiating antidepressants compared reference group treated interferons hazard ratio hr 072 95 confidence interval ci 054096 patients diagnosed depression discontinued interferon treatment higher extent patients without depression hr 151 95 ci 115198 patients fingolimod initiating antidepressant compared patients initiate antidepressant hr 147 95 ci 104208 conclusionsour results indicate choice dmt associated subsequent risk depression ms studies needed establish whether causal link overall depression use antidepressants displayed limited associations dmt discontinuation ms relapse,0.0
induction antigenspecific treg cells treating autoimmune uveitis via bystander suppressive pathways without compromising antitumor immunity abstractbackgroundinduction autoantigenspecific treg cells suppresstissuespecific autoimmunity without compromising beneficial immune responses holygrail immunotherapy autoimmune diseasesmethodsin model experimentalautoimmune uveitis eau mimics human uveitis ocular inflammation induced immunization retinal antigen interphotoreceptor retinoidbinding protein irbp mice given intraperitoneal injection cd4 antibody ab onset disease followed administration irbp eau evaluated clinically functionally splenocytes cd4+cd25 cd4+cd25+ t cells sorted cultured irbp cd3 ab t cell proliferation cytokine production assessedfindingsthe experimental approach resulted remission ocular inflammation rescue visual function mice established eau mechanistically therapeutic effect mediated induction antigenspecific treg cells inhibited irbpdriven th17 response tgf il10 dependent fashion importantly abmediated immune tolerance achieved eau mice administration retinal autoantigens arrestin limited irbp antigennonspecific bystander manner eausuppressed tolerized mice compromise antitumor t immunity melanoma modelinterpretationwe successfully addressed specific immunotherapy eau vivo induction autoantigenspecific treg cells without compromising host overall t cell immunity potential implication patients autoimmune uveitisfundingthis study supported natural science foundation guangdong province fundamental research fund state key laboratory ophthalmology zhongshan ophthalmic center,0.0
adverse reaction methylprednisolone pulse therapy acute respiratory distress syndrome clin case rep 2021 jul 16 9 7 e04468 doi 101002 ccr34468 ecollection 2021 julabstractmethylprednisolone pulse therapy significant antiinflammatory effects multiple sclerosis acute respiratory distress syndrome probable adverse effect methylprednisolone pulse therapy ms patients consideredpmid34295489 pmcpmc8283859 doi101002 ccr34468,0.0
prophylactic exposure oral riluzole reduces clinical severity immunerelated biomarkers experimental autoimmune encephalomyelitis j neuroimmunol 2021 may 7 356577603 doi 101016 jjneuroim2021577603 online ahead printabstractglutamatemediated excitotoxicity immune cell infiltration hallmarks multiple sclerosis glutamate release inhibitor riluzole ril shown attenuate clinical symptoms experimental autoimmune encephalomyelitis eae mice association glutamate excitotoxicity progression mog3555induced eae well defined study investigated effects prophylactic chronic oral ril clinical severity eae prophylactic+chronic ril reduced presence inflammatory infiltrates altered gfap foxp3 attenuated disease severity findings indicate need delineate distinct role glutamate eae symptomatologypmid33992861 doi101016 jjneuroim2021577603,0.0
identification differential dna methylation associated multiple sclerosis familybased study j neuroimmunol 2021 apr 30 356577600 doi 101016 jjneuroim2021577600 online ahead printabstractmultiple sclerosis ms caused still unknown interplay genetic environmental factors epigenetics including dna methylation represents model environmental factors influence ms risk twentysix affected 26 unaffected relatives 8 ms multiplex families analysed multicentric italian study using medipseq followed technical validation biological replication two additional families differentially methylated regions dmrs using seqcap epi choice enrichment kit roche associations medipseq across families combined aggregation statistics yielding 162 dmrs fdr 01 technical validation biological replication led 2 hypomethylated regions point ntm bai3 genes 2 hypermethylated regions pik3r1 capn13 4 novel regions contain genes potential interest need tested larger cohorts patientspmid33991750 doi101016 jjneuroim2021577600,0.0
cns demyelination tnf inhibitor exposure retrospective cohort study j neuroimmunol 2021 apr 26 356577587 doi 101016 jjneuroim2021577587 online ahead printabstractobjective study longterm outcomes patients cns demyelinating events exposed tnfainhibitors tnfai including subsequent clinical relapse mri lesions use disease modifying therapy dmt msmethods adult patients evaluated cns demyelinating disease tnfai use identified mass general brigham 01 199808 2020 analyzed clinicallyrelevant subgroups inclusion criteria required first neurological event taking tnfai mri lesions consistent demyelination absence probable alternative diagnosisresults 21 cases mean age 44 years 20 female 14 2 ms risk factors index neurological event ine median 12 months range 1176 onset tnfai use adalimumab 10 etanercept 6 infliximab 5 mri lesions often present periventricular 16 20 80 spinal zones 10 20 50 37 7 19 met 2 barkhof criteria onset csf testing abnormal 64 7 11 67 10 15 available followup mris developed new lesions median 295 months mri surveillance median mri surveillance 60 months 55 11 20 met 2 barkhof criteria 47 8 17 suffered clinical relapse median 405 months clinic followup median clinic followup since ine 26 months patients discontinuing tnfai 18 21 86 ine onset 56 10 18 evidence cns demyelination six patients 6 21 29 started ms disease modifying therapy dmt ine 50 3 6 subsequent disease activity continuing restarting tnfai followed relapse 75 3 4 65 13 20 met 2017 mcdonald criteria ms ine another 10 15 20 75 study conclusionconclusions extended followup majority patients relapsing cns demyelinating disorderas evidenced new mri lesions clinical relapsesdespite tnfai discontinuationpmid33945946 doi101016 jjneuroim2021577587,1.0
expression analysis nfkappabassociated long noncoding rnas peripheral blood mononuclear cells relapsingremitting multiple sclerosis patients j neuroimmunol 2021 may 4 356577602 doi 101016 jjneuroim2021577602 online ahead printabstractlong noncoding rnas lncrnas potential disease biomarkers might related severe course multiple sclerosis ms evaluated expression levels nfbassociated lncrnas including hotair thril h19 nkila anril well expression il6 tnf mmp9 peripheral blood mononuclear cells pbmcs 60 relapseremitting ms rrms patients relapse phase rrms upregulation anril h19 positively correlated overexpression il6 high levels thril hotair positively correlated increased levels tnf mmp9 respectively however nkila expression negatively correlated expression tnfpmid33979709 doi101016 jjneuroim2021577602,0.0
haploidentical haematopoietic stem cell transplantation malignant infantile osteopetrosis intermediate osteopetrosis retrospective analysis single centre abstractobjectiveto evaluate clinical efficacy haploidentical haematopoietic stem cell transplantation haplohsct treatment malignant infantile osteopetrosis miop intermediate osteopetrosismethodschildren miop iop underwent haplohsct beijing childrens hospital capital medical university january 2010 may 2018 retrospectively analysed data relating clinical manifestations engraftment prognosis children extracted medical recordsresultstwentyseven patients including 18 males 9 females onset age 12 00472 months enrolled study median time diagnosis transplantation 4 123 months patients received haplohsct myeloablative conditioning regimen including fludarabine busulfan cyclophosphamide graft versus host disease gvhd prophylaxis based antihuman t lymphocyte porcine immunoglobulin antihuman thymus globulin methotrexate mycophenolate mofetil median observation time 552 031262 months end followup twenty patients survived seven patients died 5 year overall survival rate 739 stage iii acute gvhd observed 20 patients stage iii gvhd 1 patient patients stage iv disease chronic gvhd observed 11 patients 407 controlled antigvhd therapyconclusionshaplohsct effective treatment miop iop high survival rate significantly improved clinical symptoms patients vision impairment hsct improvement slow transplantation incidence gvhd high mild effectively controlled appropriate treatment data indicated haplohsct feasible treatment miop iop,0.0
artificial double inversion recovery images juxta cortical lesion visualization multiple sclerosis abstractbackgroundcortical lesions highly inconspicuous magnetic resonance imaging mri double inversion recovery dir higher sensitivity conventional clinical sequences ie t1 t2 flair difficult acquire leading overseen cortical lesions clinical care clinical trialsobjectiveto evaluate usability artificially generated dir adir images cortical lesion detection compared conventionally acquired dir cdir methodsthe dataset consisted 3dt1 2dproton density pd t2 images 73 patients 49rr 20sp 4pp 15 t using 41 traintestratio fully convolutional neural network trained predict 3dadir 3dt1 2dpd t2 images randomized blind scoring test set used determine detection reliability precision recallresultsa total 626 vs 696 cortical lesions detected 15 adir vs cdir images intraclass correlation coefficient icc 092 compared cdir precision recall 084 006 076 009 respectively frontal temporal lobes showed largest differences discernibilityconclusioncortical lesions can detected good reliability artificial dir technique potential broaden availability dir clinical care provides opportunity ex post facto implementation cortical lesions imaging existing clinical trial data,0.0
author#39 s response reply quot question data importance serum amyloid level patients multiple sclerosisquot j neuroimmunol 2021 apr 30 356577589 doi 101016 jjneuroim2021577589 online ahead printno abstractpmid33962173 doi101016 jjneuroim2021577589,0.0
therapeutic prospects micrornas carried mesenchymal stem cellsderived extracellular vesicles autoimmune diseases life sci 2021 apr 5119458 doi 101016 jlfs2021119458 online ahead printabstractautoimmune diseases ads class chronic disease conditions impaired tolerance autoantigens currently effective treatment ads existing medications limitations due nonspecific targets side effects accumulating evidence shown mesenchymal stem cells mscs play role ads treatment beneficial effects mainly rely celltocell communication secretion extracellular vesicles evs soluble factors mscderived evs mscevs modulate adjacent distinct cells transferring various dna mrna noncoding rnas proteins lipids parent cells recipient cells micrornas mirnas small noncoding rnas negatively regulate multiple target genes posttranscriptional level involved chronic inflammatory immune processes compared fluid mscevs delivery can protect mirnas degradation ribonucleases ensuring mirnas able perform respective crucial roles ad recipient cells review discussed therapeutic prospects challenges mirnas secreted mscevs mscevmirnas reviewing experimentally verified therapeutic outcomes mscevmirnas several ads including rheumatoid arthritis ra autoimmune hepatitis aih asthma colitis systemic sclerosis ssc graftversushost disease gvhd pmid33831424 doi101016 jlfs2021119458,0.0
quality life multiple sclerosis dominated fatigue disability selfefficacy j neurol sci 2021 apr 9 426117437 doi 101016 jjns2021117437 online ahead printabstractbackground objective quality life multiple sclerosis ms reflects complex relationships symptoms fatigue spasticity pain bladder vision dysfunction disability health perceptions selfefficacymethods crosssectional study selfreport questionnaire pack patient reported outcome measures collected 5695 people ms pwms alongside clinical data neurologists patient reported outcome measure converted intervalscaled estimates following fit rasch model patient reported outcome measures well perceived health age disease subtype gender subject path analysis analyse relationships quality life qol guided wilson clearly conceptual frameworkresults final model explains 812 variance qol fatigue clearly dominant suggesting means intervene improve qol next influential factors disability selfefficacy similar effect levels model can replicated pwms disease modifying therapy largely invariant gender disease subtype age insignificant effectconclusions order promote better qol ms care include management fatigue interventions ameliorate disability support enhance selfefficacy range skills needed treatments will require input medical nursing therapy psychology staff findings provide evidence substantiating need pwms provided care comprehensive multidisciplinary teamspmid33991718 doi101016 jjns2021117437,0.0
uncommon disease included commonly differential diagnosis neurological diseases neurobehet#39 s syndrome j neurol sci 2021 apr 20 426117436 doi 101016 jjns2021117436 online ahead printabstractbehets syndrome bs may present different neurological problems related either directly primary indirectly secondary bs primary neurological involvement named neurobehcets syndrome nbs two major subtypes classified mainly clinical mri findings 1 parenchymalnbs pnbs 2 extra parenchymal neurovascular involvement mostly seen cerebral dural venous sinus thrombosis cvst less commonly seen forms nbs cognitive behavioral syndromes peripheral nervous system involvement parenchymalnbs common clinical neurological presentation bs rare disease distinct mri features often included differential diagnosis neurovascular neuroinflammatory disorders commonly affected neuroanatomical site pnbs mesodiencephalic junction mdj followed pontobulbar thalamic regions basal ganglia spinal cord varied locations may explain certain extent bs considered differential many neurological disorders relatively common form nbs results cvst may also confused conditions resulting cvst especially systemic clinical features suggestive bs missedpmid33984547 doi101016 jjns2021117436,0.0
smartphone sensorbased digital outcome assessment multiple sclerosis abstractbackgroundsensorbased monitoring tools fill critical gap multiple sclerosis ms research clinical careobjectivethe aim study assess performance characteristics floodlight proofofconcept poc appmethodsin 24week study clinicaltrialsgov nct02952911 smartphonebased active tests passive monitoring assessed cognition electronic symbol digit modalities test upper extremity function pinching test draw shape test gait balance static balance test uturn test walk test passive monitoring intraclass correlation coefficients iccs age sexadjusted spearmans rank correlation determined testretest reliability correlations clinical magnetic resonance imaging mri outcome measures respectivelyresultsseventysix people ms pwms 25 healthy controls enrolled pwms iccs moderatetogood icc 2 1 061085 across tests correlations domainspecific standard clinical disability measures significant tests cognitive r 082 p 0001 upper extremity function r 040064 p 0001 gait balance domains r 025 052 p 005 except static balance test r 020 p 005 tests also correlated expanded disability status scale 29item multiple sclerosis impact scale items subscales normalized brain volumeconclusionthe floodlight poc app captures reliable clinically relevant measures functional impairment ms supporting potential use clinical research practice,1.0
neuroprotective role galantamine without physical exercise experimental autoimmune encephalomyelitis rats life sci 2021 apr 6119459 doi 101016 jlfs2021119459 online ahead printabstractaims fact physical activity besides central cholinergic enhancement contributes improving neuronal function spastic plasticity recommends use anticholinesterase cholinergic drug galantamine without exercise management experimental autoimmune encephalomyelitis eae model multiple sclerosis ms materials methods sedentary 14 days exercised male sprague dawley rats subjected eae hereafter exercised rats continued rotarod 30 min 17 consecutive days onset symptoms day 13 eae sedentary exercised groups subdivided untreated posttreated galantamine disease progression assessed eae score motor performance biochemically using cerebrospinal fluid csf cerebellum brain stem samples used histopathology immunohistochemistry analysiskey findings galantamine decreased eae score sedentary exercised rats enhanced motor performance galantamine without exercise inhibited csf levels tumor necrosis factor tnf interleukin il 6 bcl2associated x protein bax besides caspase3 forkhead box p3 foxp3 expression brain stem contrariwise elevated csf levels brain derived neurotrophic factor bdnf bcell lymphoma bcl2 enhanced remyelination cerebral neurons noteworthy exercise boosted drug effect bcl2 baxsignificance neuroprotective effect galantamine eae associated antiinflammatory antiapoptotic potentials along increasing bdnf remyelination also normalized regulatory tcells levels brain stem impact addon exercise markedly manifested reducing neuronal apoptosispmid33836162 doi101016 jlfs2021119459,1.0
role 5ht 2b receptors fluoxetinemediated modulation th17 th1cells multiple sclerosis j neuroimmunol 2021 may 12 356577608 doi 101016 jjneuroim2021577608 online ahead printabstractfluoxetine selective serotonin reuptake inhibitor also immunomodulatory effect investigated effects fluoxetine serotonin 5ht proinflammatory th17 th1cells 30 patients relapsingremitting ms 20 healthy subjects fluoxetine 5ht suppressed il17 ifn gmcsf production stimulated d4+ tcells groups blockade 5ht2breceptors decreased inhibitory effect fluoxetine cytokine production ms patients finally 5ht2breceptor activation inhibits il17 ifn gmcsf production groups data suggest antiinflammatory role fluoxetine ms mediated activation 5ht2breceptorspmid34000471 doi101016 jjneuroim2021577608,0.0
remyelination enhanced astragalus polysaccharides inducing differentiation oligodendrocytes neural stem cells cuprizone model demyelination brain res 2021 mar 29147459 doi 101016 jbrainres2021147459 online ahead printabstractdemyelination hallmark multiple sclerosis ms promoting remyelination important strategy treat ms previous study showed astragalus polysaccharides aps main bioactive component astragalus membranaceus prevent demyelination experimental autoimmune encephalomyelitis mice investigate effects aps remyelination underlying mechanisms study set cuprizoneinduced demyelination model mice treated aps found aps relieved neurobehavioral dysfunctions caused demyelination efficaciously facilitated remyelination vivo order determine whether mechanism enhancing remyelination associated differentiation neural stem cells nscs biomarkers nscs astrocytes oligodendrocytes neurons measured corpus callosum tissues mice realtime pcr western blot immunohistochemistry assays data revealed aps suppressed stemness nscs reduced differentiation nscs astrocytes promoted differentiation oligodendrocytes neurons phenomenon confirmed differentiation model c172 nscs cultured vitro since sonic hedgehog signaling pathway proven crucial differentiation nscs oligodendrocytes examined expression levels key molecules pathway vivo vitro eventually found aps activated signaling pathway together results demonstrated aps probably activated sonic hedgehog signaling pathway first induced nscs differentiate oligodendrocytes promoted remyelination suggested aps might potential candidate treating mspmid33794147 doi101016 jbrainres2021147459,1.0
preliminary testing patient decision aid patients relapsingremitting multiple sclerosis mult scler j exp transl clin 2021 jul 15 7 3 20552173211029966 doi 101177 20552173211029966 ecollection 2021 julsepabstractbackground multiple firstline disease modifying therapies dmts available relapsingremitting multiple sclerosis rrms different characteristics developed interactive patient decision aid ptda promote informed shared decisionmaking sdm objective test preliminary effectiveness ptda participants rrmsmethods knowledge decisional conflict measured pre post implementation ptda sdm consultation 6month treatment patterns observed differences scores analyzed using descriptive statistics paired ttests qualitative interviews patients neurologists analyzed using thematic analysisresults 52 participants recruited female 81 40 years age younger 62 experienced ms less 5 years 56 participants used ptda significant improvement decisional conflict change 100 p 0001 knowledge change 215 p 0001 nearly patients wanted sdm 25 56 reported occurred consult qualitative results suggested ptda supported patients neurologists making decisionsconclusion pilot study suggests ptda use helps rrms patients clinician select dmt future studies will assess feasibility implementation impact ptda timely dmt initiation longerterm adherencepmid34350027 pmcpmc8287362 doi101177 20552173211029966,0.0
comparable efficacy safety teriflunomide versus dimethyl fumarate treatment relapsingremitting multiple sclerosis neurol res int 2021 jul 15 20216679197 doi 101155 2021 6679197 ecollection 2021abstractbackground aim observational study investigate efficacy safety two approved oral diseasemodifying therapies dmts patients remittingrelapsing multiple sclerosis rrms dimethyl fumarate dmf vs teriflunomide trf methods total 159 rrms patients 82 trf 77 dmf included expanded disability status scale edss confirmed disability improvement cdi confirmed disability progression cdp annualized relapse rate arr evaluated twoyear period prior enrollment study drugassociated adverse effects aes recorded conducted propensity matching score compare efficacy trf dmfresults matching confounders trf dmftreated groups different terms edss p value 054 cdi p value 080 cdp p value 039 arr p value 005 trf discontinuation occurred 2 patients 243 due mediastinitis liver dysfunction patient 129 discontinued dmf due depression incidence rate aes trftreated group 814 hair thinning hair loss 629 nail loss 209 elevated aminotransferase 148 common aes dmftreated patients aes 882 predominance flushing 732 pruritus 169 abdominal pain 169 conclusion based findings dmf efficacious safe trf treatment rrms iranian study population multicentric studies need corroborate findings populationspmid34336283 pmcpmc8298169 doi101155 2021 6679197,1.0
patient concurrent multiple sclerosis moyamoya disease background moyamoya disease mmd rare vasculopathy multiple sclerosis ms autoimmune disease causes cns demyelination literature focused misdiagnosis mmd msmimic present patient coexisted methods case report results 57yearold woman presented gait dysfunction paresthesias feet mri revealed brain spinal cord lesions consistent ms vessel imaging revealed multivessel stenosis consistent mmd lumbar puncture demonstrated oligoclonal bands leading two diagnoses ms mmd conclusions ms can exist concurrently mmd potentially due underlying propensity autoimmunity,1.0
systemic sclerosis associated interstitial lung disease nintedanib rare disease promising drug cureus 2021 jul 15 13 7 e16404 doi 107759 cureus16404 ecollection 2021 julabstractsystemic sclerosisassociated interstitial lung disease sscild rare disease progressive nature eventually leading lung fibrosis nintedanib tyrosine kinase inhibitor widely accepted drug treating idiopathic pulmonary fibrosis ipf disease shares similarities sscild regarding pathological disease processes review aim discuss pathogenesis sscild overall role nintedanib management sscild sscild involves multiple pathological mediators contributing various pathways ultimately cause lung fibrosis pathogenesis sscild complex phenomenon still needs study nintedanib demonstrated efficacy treatment sscild reducing progression pathological process also proven clinical significance management sscild however currently available literature evidence compare effectiveness nintedanib already available treatment modalities cyclophosphamide cyc mycophenolate mofetil mmf azathioprine azt current literature also lacks information nintedanibs longterm consequences patients sscild therefore create better evidencebased treatment guidelines recommend researchers conduct randomized clinical trials comparing nintedanib mmf cyc azt etc continue surveillance explore longterm consequences nintedanibpmid34414042 pmcpmc8364831 doi107759 cureus16404,0.0
lower extremity muscle power critical determinant physical function aging multiple sclerosis exp gerontol 2021 apr 16111347 doi 101016 jexger2021111347 online ahead printabstractbackground purpose aging lower extremity muscle power undoubtedly one important parameters neuromuscular function implicating lower extremity physical function eg walking capacity however previous studies examined combined effects aging multiple sclerosis ms lower extremity muscle power concomitant lower extremity physical function aim crosssectional study examine potential decrements pwms vs healthy controls hc across adult lifespan outcomesmethods present explorative crosssectional study n 42 pwms females n 29 69 age 53 12 years mean sd range 3178 patient determined disease steps score 37 17 range 07 n 49 agematched hc females n 34 69 age 56 16 years range 2478 enrolled divided groups young 44 years middleaged 4559 years old 60 years muscle power obtained bilateral leg press powerlegpresspeak maximal chair rise powerchairrise using linear encoder associations assessed muscle power measurements lower extremity physical function 5 x sittostand 5sts timed 25footwalktest t25fwt results muscle power reduced pwms vs hc powerlegpresspeak 23 3412 mean 95ci powerchairrise 26 3517 negatively associated advanced age pwms decline per decade 040 wkg1 253 wkg1 respectively hc decline per decade 042 wkg1 203 wkg1 respectively muscle power strongly associated physical function pwms r2range 045061 p 001 yet moderately associated hc r2range 018039 p 001 conclusion combined effects ms aging reveal substantial decrements lower extremity muscle power accompanied strongly associated decrements lower extremity physical function consequently lower extremity muscle power viewed clinically important factor ie critical determinant lower extremity physical function pwms propose lower extremity muscle power specifically targeted preventive rehabilitative exercise strategies especially older pwmspmid33872737 doi101016 jexger2021111347,0.0
relapsingremitting multiple sclerosis arising patient atopic dermatitis dupilumab jaad case rep 2021 jul 15 153335 doi 101016 jjdcr202107003 ecollection 2021 sepno abstractpmid34401425 pmcpmc8349746 doi101016 jjdcr202107003,0.0
optical coherence tomography angiography indicates subclinical retinal disease neuromyelitis optica spectrum disorders abstractbackgroundneuromyelitis optica spectrum disorders nmosd neuroinflammatory diseases central nervous system patients suffer recurring relapses unclear whether relapseindependent disease activity occurs whether clinical relevanceobjectiveto detect diseasespecific alterations retinal vasculature reflect disease activity nmosdmethodscrosssectional analysis 16 patients nmosd 21 patients relapsingremitting multiple sclerosis 21 healthy controls using retinal optical coherence tomography oct optical coherence tomography angiography octa measurement glial fibrillary acidic protein gfap serum levels assessment visual acuityresultspatients nmosd multiple sclerosis revealed lower foveal thickness ft p 002 measures increase foveal avascular zone faz p 002 compared healthy controls independent optic neuritis reduced ft p 001 enlarged faz areas p 00001 vessel loss superficial vascular complex p 001 linked higher serum gfap levels superficial vessel loss associated worse visual performance patients nmosd irrespective optic neuritisconclusionsubclinical parafoveal retinal vessel loss might occur nmosd might linked astrocyte damage poor visual performance octa may tool study subclinical disease activity nmosd,0.0
modeling compartmentalized chronic immunemediated demyelinating cns disease biozzi abh mouse j neuroimmunol 2021 apr 21 356577582 doi 101016 jjneuroim2021577582 online ahead printabstractwe explored whether experimental autoimmune encephalomyelitis eae biozzi mice recapitulates temporal dynamics tissue injury immunepathogenesis cns compartmentalization occurring progressive multiple sclerosis ms chronic eae exhibited relapsing progressing disease partial closure bbb reduced tissue inflammatory activity development meningeal ectopic lymphoid tissue directly opposing potentially driving spinal subpial demyelinated plaques t cell predominant disease relapses transformed b cell predominant disease late chronic eae high serum antimog reactivity thus late chronic biozzi eae recapitulates essential features progressive ms suitable developing disease modifying regenerative therapiespmid33910137 doi101016 jjneuroim2021577582,1.0
road conception women multiple sclerosis mult scler j exp transl clin 2021 jul 15 7 3 20552173211032313 doi 101177 20552173211032313 ecollection 2021 julsepabstractobjective objective prospective real world study gain insight different roads conception women ms take part prospective canadian multiple sclerosis pregnancy study canpregms methods participants women ms planning pregnancy data cutoff analyses april 30 2020results believe first prospective national study women ms planning pregnanciesthe data first 44 women enrolled 26 achieved pregnancy cutoff date seven women used assisted reproductive technologies arts 6 stopped disease modifying therapy dmt neurologists recommendations 6 interruption s trying conceive due ms relapses mridetected inflammation limited windows opportunity dmt coursesconclusion study illustrates roads women take conception even therapy similar clinical expression ms advice given treating neurologists washout periods show discrepancies paper highlights real problem definitive international consensus managing women due lack real world data thus goal canpregms provide real world datapmid34350028 pmcpmc8287372 doi101177 20552173211032313,0.0
risk assessment interstitial lung disease incremental prognostic value cardiopulmonary ultrasound background mortality risk chronic interstitial lung disease ild currently assessed using ildgap score present study evaluates whether addition cardiopulmonary ultrasound parameters ildgap score can improve predictive value ildgapmethodsmedical records 91 patients ild hospitalized june 2015 march 2016 retrospectively examined lung ultrasound lus score right ventricular rv function mechanics obtained cardiopulmonary ultrasound ildgap score calculated demographic characteristics pulmonary function parameters patients followed may 2020 primary endpoint allcause deathresultsafter exclusions 74 patients ild included analysis followup period 36 patients ild survived ilds 38 patients died ildd compared ilds ildd cases exhibited higher number blines lus score rv enddiastolic base dimension rvd lower rv function multivariate analysis ildgap score hazard ratio 288 95 ci 138599 p 0005 lus score hazard ratio 113 95 ci 104124 p 0006 rvd hazard ratio 109 95 ci 103116 p 0004 significantly related risk death adding lus score rvd ildgap score significantly improved predictive value compared ildgap score alone c statistics 090 vs 076 p 0018 conclusionwe investigated utility new prognostic model ild includes cardiopulmonary ultrasound parameters lus score rvd ildgap score model better reflects severity pulmonary fibrosis cardiac involvement incremental predictive value ildgap score alone,0.0
vision improvement osimertinib treatment paraneoplastic optic neuropathy associated lung adenocarcinoma case rep ophthalmol med 2021 jul 15 20212832021 doi 101155 2021 2832021 ecollection 2021abstracttreatments paraneoplastic optic neuropathy pon tumorrelated autoimmune disease include immunosuppression plasma exchange immunoglobulin therapies well treatment underlying disease herein describe clinical course older adult patient pon whose loss vision improved switching epidermal growth factor receptortyrosine kinase inhibitor egfrtki treatments cancer 76yearold woman treated gefitinib lung adenocarcinoma two years presented acute bilateral visual disturbances decimal bestcorrected visual acuity bcva 03 right eye re 07 left eye le slitlamp examination funduscopy showed abnormal findings two weeks later bcva decreased 02 re 001 le goldmans perimetry showed defect lower nasal re extensive visualfield loss le singleflash electroretinograms showed normal amplitudes magnetic resonance imaging revealed left optic neuritis showed neither metastatic cancer multiple sclerosis patternreversal visual evoked potentials showed decreased p100 amplitudes eyes based diagnosis pon clinical findings methylprednisolone pulse treatment administered however bcva became light perception two months first visit tumor tissue found positive egfr t790m resistance mutation bronchoscopy egfrtki treatment changed osimertinib decreasing size lung cancer lesions bcva improved hand motion final bcva 001 re counting fingers 10 cm le died age 79 years knowledge reports shown improvement bcva patients pon changing egfrtki treatments report indicates patients may develop severe visual dysfunction without early treatment primary tumorpmid34327032 pmcpmc8302396 doi101155 2021 2832021,0.0
safety efficacy covid19 vaccines multiple sclerosis patients j neuroimmunol 2021 may 4 356577599 doi 101016 jjneuroim2021577599 online ahead printabstractcovid19 vaccination recommended multiple sclerosis patients diseasemodifying therapies can influence safety efficacy covid19 vaccines rna dna protein inactivated vaccines likely safe multiple sclerosis patients incidences central demyelination reported viral vector vaccines benefits likely outweigh risks alternatives unavailable liveattenuated vaccines avoided whenever possible treated patients interferonbeta glatiramer acetate teriflunomide fumarates natalizumab expected impact vaccine efficacy celldepleting agents ocrelizumab rituximab ofatumumab alemtuzumab cladribine sphingosine1phosphate modulators will likely attenuate vaccine responses coordinating vaccine timing dosing regimens therapies may optimize vaccine efficacypmid34000472 doi101016 jjneuroim2021577599,1.0
greek validation study multiple sclerosis work difficulties questionnaire23 healthcare basel 2021 jul 15 9 7 897 doi 103390 healthcare9070897abstractthe multiple sclerosis work difficulties questionnaire23 mswdq23 selfreport instrument developed assess barriers faced people multiple sclerosis pwms workplace aim study explore psychometric properties greek version mswdq23 study sample consisted 196 pwms currently working part fulltime jobs participants underwent clinical examination cognitive screening brief international cognitive assessment multiple sclerosis bicams completed selfreport measures fatigue psychological functioning quality life along mswdq23 questionnaire confirmatory factor analysis cfa performed goodnessoffit measures used evaluate construct validity convergent validity checked correlating mswdq23 scores study measures cronbachs alpha value produced assess internal consistency cfa yielded model fair fit confirming threefactor structure instrument higher work difficulties associated higher expanded disability status scale edss scores poorer cognitive function fatigue stress anxiety depression poorer health status supporting convergent validity mswdq23 internal consistency cronbachs alpha 094 testretest reliability icc 0996 95 ci 09900998 excellent greek mswdq23 can considered valid patientreported outcome measure can used interventions aiming improve vocational status pwmspmid34356274 doi103390 healthcare9070897,0.0
antinmda receptor encephalitis overlapping demyelinating disorder 20year old female borderline personality disorder proposal diagnostic therapeutic algorithm autoimmune encephalitis psychiatric patients case report background antinmda receptor encephalitis nmdare autoimmune encephalitis ae mainly affecting young females typically presents isolated psychiatric symptoms eg depressed mood first neurological abnormalities eg seizures movement disorders develop later thus high risk overlooking nmdare patients preexisting psychiatric illness due symptom overlap prodromal period disease treatment effective although rare concomitant sequential development demyelinating disorder increasingly recognized associated disease entity overlap syndrome immediate diagnostic therapeutic implicationscase presentationwe report patient borderline personality disorder bpd developed nmdare overlapping demyelinating disorder antimyelin oligodendrocyte glycoprotein mog igg positivity initial clinical presentation predominantly affective symptoms eg mood lability anxiety depressed mood lead us suspect exacerbation bpd first however acute changes premorbid behavior newly developed psychotic symptoms memory deficits lead us correct diagnosis ae complicated development demyelinating disorder result impaired illness awareness psychosis diagnostic treatment difficult carry symptoms completely remitted treatment methylprednisolone 1 g daily 5 days 5 cycles plasma exchangeconclusionscontinuous awareness neuropsychiatric clinical warning signs patients prediagnosed psychiatric disorder important timely diagnosis therefore believe diagnostic therapeutic algorithm provided first time specifically addressing patients preexisting psychiatric illness integrating overlap syndromes can useful tool moreover order timely perform diagnostics treatment judicial approval obtained rapidly,1.0
functional connectivity multiple sclerosis modelled connectome stability 5year followup study abstractbackgroundbrain functional connectivity fc multiple sclerosis ms abnormal compared healthy controls hcs longitudinal studies ms needed evaluate whether fc stability clinically relevantobjectiveto compare functional magnetic resonance imaging fmri based fc ms hc determine relationship longitudinal fc changes structural brain damage cognitive performance physical disabilitymethodst1weighted mprage restingstate fmri 15t acquired 70 relapsingremitting ms patients 94 matched hc baseline mean months since diagnosis 140 11 60 ms patients 5 years independent component analysis network modelling used measure longitudinal fc stability crosssectional comparisons hc linear mixed models adjusted age sex used calculate correlationsresultsat baseline patients ms showed fc abnormalities within networks single connections compared hc longitudinal analyses revealed functional stability significant relationships clinical disability cognitive performance lesion brain volumeconclusionfc abnormalities occur already first decade ms yet found relevant clinical correlations network deviations future largescale longitudinal fmri studies across range ms subtypes outcomes required,0.0
ski expression suppresses pathogenic th17 cell response mitigates experimental autoimmune encephalomyelitis front immunol 2021 jul 15 12707899 doi 103389 fimmu2021707899 ecollection 2021abstractpathogenic th17 cells critically involved many autoimmune diseases nonpathogenic th17 cells immune regulatory understanding mechanisms induction maintenance pathogenic th17 cells will benefit development therapeutic treatments related diseases shown transforming growth factor tgf induced ski degradation dissociation smad4 complex prerequisite tgfinduced th17 cell differentiation however unclear whether ski regulates pathogenic th17 differentiation require tgf cytokine showed ski expression downregulated pathogenic th17 cell differentiation ectopic expression ski abrogated differentiation pathogenic th17 cells functionally using knockin mouse model found ectopic ski expression specifically t cells prevented myelin oligodendrocyte glycoprotein peptide mog3355 induced experimental autoimmune encephalomyelitis eae animal model human multiple sclerosis revealed induced ski expression already differentiated pathogenic th17 cells reduced maintenance th17 program ameliorated eae adoptive t cell transfer model therefore study provides valuable insights targeting ski modulate pathogenic th17 cell function treat th17related diseasespmid34335622 pmcpmc8321777 doi103389 fimmu2021707899,1.0
ponesimod modulates th1 th17 treg cell balance ameliorates disease experimental autoimmune encephalomyelitis j neuroimmunol 2021 apr 23 356577583 doi 101016 jjneuroim2021577583 online ahead printabstractsphingosine1phosphate receptor 1 s1p1 plays important role autoimmune disease evaluated whether ponesimod s1p1 modulator affects inflammation experimental autoimmune encephalomyelitis eae investigated th1 th2 th17 treg cell subsets ponesimod treatment ameliorated eae alleviated inflammatory infiltration compared untreated eae ponesimodtreated mice lower th1 th17 cell numbers higher treg cell numbers ifn tbet il17 rort levels well pmtor mtor ratio diminished tgf foxp3 levels enhanced results suggest ponesimod modulates th1 th17 treg balance regulates mtor pathwaypmid33940233 doi101016 jjneuroim2021577583,0.0
comorbidities primary headache disorders literature review metaanalysis background primary headache disorders common burdensome conditions associated several comorbidities cardiovascular psychiatric ones turn contribute global burden headache aim study provide comprehensive description pooled prevalence comorbidities primary headache disorders using metaanalytical approach based studies published 2000 2020methodsscopus searched primary research clinical population studies medical comorbidities described adults primary headache disorders comorbidities extracted using taxonomy derived global burden disease gbd study compared prevalence comorbidities among headache sufferers general population using gbd2019 estimates compared comorbidities proportions clinical vs population studies age genderresultsa total 139 studies reporting information 419 million subjects primary headaches included total 275 million comorbidities reported median per subject 064 interquartile range 032107 frequently addressed comorbidities depressive disorders addressed 51 studies pooled proportion 23 95 ci 2026 hypertension addressed 48 studies pooled proportion 24 95 ci 2226 anxiety disorders addressed 40 studies pooled proportion 25 95 ci 2228 conditions anxiety depression back pain prevalence among headache sufferers higher gbd2109 estimates associations average age female prevalence within studies showed hypertension frequent studies higher age less females whereas fibromyalgia restless leg syndrome depressive disorders frequent studies younger age femaleconclusionssome relevant comorbidities primary headache disorders back pain anxiety depression diabetes ischemic heart disease stroke among burdensome conditions together headache according gbd study joint treatment headaches comorbidities may positively impact headache sufferers health status contribute reduce impact group highly burdensome diseases,0.0
ckd506 novel hdac6selective inhibitor exerts therapeutic effects rodent model multiple sclerosis sci rep 2021 jul 14 11 1 14466 doi 101038 s41598021932326abstractdespite advances therapeutic strategies multiple sclerosis ms therapy options remain limited various adverse effects therapeutic potential ckd506 novel hdac6selective inhibitor ms evaluated mice myelin oligodendrocyte glycoprotein3555 mog3555 induced experimental autoimmune encephalitis eae various treatment regimens ckd506 exerted prophylactic therapeutic effects regulating peripheral immune responses maintaining bloodbrain barrier bbb integrity mog3555restimulated splenocytes ckd506 decreased proliferation downregulated expression ifn il17a ckd506 downregulated levels proinflammatory cytokines blood eae mice additionally ckd506 decreased leakage intravenously administered evans blue spinal cord cd4+ t cells cd4cd11b+cd45+ macrophage microglia spinal cord also decreased moreover ckd506 exhibited therapeutic efficacy ms even drug administration discontinued day 15 posteae induction disease exacerbation observed fingolimod changed ckd506 day 15 posteae induction ckd506 alleviated depressionlike behavior presymptomatic stage eae conclusion ckd506 exerts therapeutic effects regulating t cell macrophagemediated peripheral immune responses strengthening bbb integrity results suggest ckd506 potential therapeutic agent mspmid34262061 doi101038 s41598021932326,1.0
effects exposure surrounding green air pollution traffic noise nonaccidental causespecific mortality dutch national cohort background everyday people exposed multiple environmental factors surrounding green air pollution traffic noise exposures generally spatially correlated hence estimating associations surrounding green air pollution traffic noise health outcomes exposures taken account aim study evaluate associations longterm residential exposure surrounding green air pollution traffic noise mortalitymethodswe followed approximately 105 million adults aged 30 years living netherlands 1 january 2013 31 december 2018 used cox proportional hazard models evaluate associations residential surrounding green including average normalized difference vegetation index ndvi buffers 300 1000 m annual average ambient air pollutant concentrations including particulate matter pm25 nitrogen dioxide no2 traffic noise nonaccidental causespecific mortality adjusting potential confoundersresultsin singleexposure models surrounding green negatively associated mortality outcomes air pollution positively associated outcomes twoexposure models associations surrounding green air pollution attenuated remained respiratory mortality twoexposure model no2 ndvi 300 m hr no2 1040 95ci 1022 1059 per iqr increase 83 g m3 hr ndvi 300 m 0964 95ci 0952 0976 per iqr increase 014 roadtraffic noise positively associated lung cancer mortality also adjustment air pollution surrounding greenconclusionslower surrounding green higher air pollution associated higher risk nonaccidental causespecific mortality studies including one correlated exposures may overestimate associations mortality exposure,0.0
predictors osteoradionecrosis following irradiated tooth extraction background tooth extraction post radiotherapy one important risk factors osteoradionecrosis jawbones objective study determine predictors osteoradionecrosis orn associated dental extraction post radiotherapy methodsa retrospective analysis medical records dental panoramic tomogram dpt patients history head neck radiotherapy underwent dental extraction august 2005 october 2019 conducted resultsseventythree patients fulfilled inclusion criteria 16 219 orn post dental extraction 389 teeth extracted 33 sockets 85 developed orn univariate analyses showed significant associations orn following factors tooth type tooth pathology surgical procedure primary closure target volume total dose timing extraction post radiotherapy bony changes extraction site visibility lower upper cortical line mandibular canal using multivariate analysis odds developing orn surgical procedure 650 ci 1373091 p 002 dental extraction 5 years radiotherapy invisible upper cortical line mandibular canal dpt odds 006 ci 001025 p 0001 947 ci 1615588 p 001 respectivelyconclusionextraction 5 years radiotherapy surgical removal procedure invisible upper cortical line mandibular canal dpt predictors orn,0.0
role t cell senescence neurological diseases regulation cellular metabolism front immunol 2021 jul 14 12706434 doi 103389 fimmu2021706434 ecollection 2021abstractimmunosenescence state dysregulated leukocyte function characterised arrested cell cycle telomere shortening expression markers cellular stress secretion proinflammatory mediators immunosenescence principally develops aging may also induced pathological settings chronic viral infections autoimmune diseases appearance senescent immune cells shown potentially cause chronic inflammation tissue damage suggesting important role process organismal homeostasis particular presence senescent t lymphocytes reported neurological diseases works pointing towards direct connection t cell senescence inflammation neuronal damage minireview provide overview role t cell senescence neurological disorders particular multiple sclerosis alzheimer disease also discuss recent literature investigating metabolic remodelling controls development senescence phenotype t cells targeting metabolic pathways involved induction senescent t cells may indeed represent novel approach limit inflammatory activity prevent neuroinflammation neurodegenerationpmid34335619 pmcpmc8317490 doi103389 fimmu2021706434,0.0
guselkumab demonstrated independent treatment effect reducing fatigue adjustment clinical responseresults two phase 3 clinical trials 1120 patients active psoriatic arthritis background interleukin23p19subunit inhibitor guselkumab effectively treats signs symptoms psoriatic arthritis psa evaluated effect guselkumab fatiguemethodsacross two phase 3 trials guselkumab discover1 discover2 patients active psa despite standard therapy randomized subcutaneous injections guselkumab 100 mg every 4 weeks q4w n 373 guselkumab 100 mg week 0 week 4 q8w n 375 placebo n 372 week 24 patients placebo group crossed guselkumab q4w fatigue measured secondary endpoint using functional assessment chronic illness therapy facit fatigue instrument range 052 higher scores indicate less fatigue leastsquares mean changes facitfatigue scores compared treatments using mixedeffect model repeated measures mediation analysis used adjust indirect effects fatigue deriving improvement outcomes including 20 improvement american college rheumatology criteria acr20 prespecified minimal disease activity mda post hoc creactive protein crp post hoc resultsbaseline mean sd facitfatigue scores discover1 n 381 discover2 n 739 ranging 291 95 314 101 indicated substantial levels fatigue relative united states general population 436 94 across studies mean improvements proportions patients 4point improvements facitfatigue scores week 24 guselkumab q4w q8w 5676 5463 respectively larger vs placebo 2236 3546 improvement facitfatigue scores guselkumab sustained week 24 week 52 moderatetolarge effect sizes cohens d 052081 week 24 066091 week 52 mediation analyses demonstrated substantial proportions effects guselkumab vs placebo fatigue direct effect adjusting achievement acr20 q4w 6970 q8w 1236 direct effect mda 7292 across dosing regimens response change serum crp concentrations 8288 across dosing regimens conclusionsin patients active psa guselkumab 100 mg q4w q8w led clinically meaningful sustained improvements fatigue 1 year substantial portion improvement facitfatigue scores induced guselkumab independent effects achievement select outcomestrial registrationname registry clinicaltrialsgovtrial registrations discover1 nct03162796 discover2 nct03158285date registration discover1 may 22 2017 discover2 may 18 2017urls trial registry recorddiscover1 https clinicaltrialsgov ct2 show nct03162796termnct03162796draw1rank1discover2 https clinicaltrialsgov ct2 show nct03158285termnct03158285draw2rank1,0.0
multiplenoncovalentinteractionstabilized layered dionjacobson perovskite efficient solar cells nano lett 2021 jun 23 doi 101021 acsnanolett1c01505 online ahead printabstracttwodimensional dionjacobson dj perovskites shown improved structure stability comparison ruddlesdenpopper rp perovskites however mechanism behind improved stability still largely unexplored multifluorinated aromatic spacer namely 4fphdma successfully developed 2d dj perovskites found 2d dj perovskite 4fphdma spacer exhibits high dissociation energy due multiple noncovalent interactions optimized 2d dj device based 4fphdma spacer n 4 exhibits champion efficiency 1662 much improved light thermal stability efficiency much higher control device using unfluorinated spacer n 4 pce 1011 among highest efficiencies aromaticspacerbased 2d dj perovskite solar cells pscs work highlights importance incorporating multiple noncovalent interactions 2d dj perovskite employing multifluorinated aromatic spacer achieve dj pscs high efficiency high stabilitypmid34161102 doi101021 acsnanolett1c01505,0.0
haplotyperesolved germline somatic alterations renal medullary carcinomas background renal medullary carcinomas rmcs rare kidney cancers occur adolescents young adults african ancestry although rmc associated sickle cell trait somatic loss tumor suppressor smarcb1 ancestral origins rmc remain unknown characterization structural variants svs involving smarcb1 rmc remains limitedmethodswe used linkedread genome sequencing reconstruct germline somatic haplotypes 15 unrelated patients rmc registered childrens oncology group cog aren03b2 study 2006 2017 prior study performed finemapping hbb locus assessed germline cancer predisposition genes subsequently assessed tumor samples mutations outside smarcb1 integrated rna sequencing interrogate structural variants smarcb1 locusresultswe find haplotype sickle cell mutation patients rmc originated three geographical regions africa addition finemapping hbb locus identified sickle cell mutation sole candidate variant identify smarcb1 structural variants characterized blunt 1bp homology eventsconclusionsour findings suggest rmc arise single founder population hbs allele strong candidate germline allele confers risk rmc furthermore find svs disrupt smarcb1 function likely repaired nonhomologous endjoining findings highlight haplotypebased analyses using linkedread genome sequencing can applied identify potential risk variants small rare disease cohorts provide nucleotide resolution structural variants,0.0
targeting immune modulators glioma avoiding autoimmune conditions cancers basel 2021 jul 14 13 14 3524 doi 103390 cancers13143524abstractcommunication signals signaling pathways often studied different physiological systems however become abundantly clear immune system selfregulated functions close association nervous system neuralimmune interface complex balance determines cancer progression well autoimmune disorders immunotherapy remains promising approach context glioblastoma multiforme gbm primary obstacle finding effective therapies potent immunosuppression induced gbm antiinflammatory cytokines induction regulatory t cells expression immune checkpoint molecules key mediators immunosuppression tumor microenvironment immune checkpoint molecules ligandreceptor pairs exert inhibitory stimulatory effects immune responses past decade extensively studied preclinical clinical trials diseases cancer autoimmune diseases immune system failed maintain homeostasis review will discuss promising immunemodulatory targets focus current clinical research glioblastoma also precarious position potentially becoming starting points development autoimmune diseases like multiple sclerosispmid34298735 doi103390 cancers13143524,0.0
made measure patienttailored treatment multiple sclerosis using cellbased therapies int j mol sci 2021 jul 14 22 14 7536 doi 103390 ijms22147536abstractcurrently still cure multiple sclerosis ms autoimmune neurodegenerative disease central nervous system treatment options predominantly consist drugs affect adaptive immunity lead reduction inflammatory disease activity broad range possible cellbased therapeutic options explored treatment autoimmune diseases including ms review aims provide overview recent future advances development cellbased treatment options induction tolerance ms will focus haematopoietic stem cells mesenchymal stromal cells regulatory t cells dendritic cells will also focus less familiar cell types used cell therapy including b cells natural killer cells peripheral blood mononuclear cells will address key issues regarding depicted therapies highlight major challenges lie ahead successfully reverse autoimmune diseases ms minimising side effects although cellbased therapies well known used treatment several cancers cellbased treatment options hold promise future treatment autoimmune diseases general ms particularpmid34299154 doi103390 ijms22147536,0.0
loss tsc1 cerebellar purkinje cells induces transcriptional translation changes fmrp target transcripts elife 2021 jul 14 10e67399 doi 107554 elife67399abstracttuberous sclerosis complex tsc genetic disorder associated multiple neurological manifestations previously demonstrated tsc1 loss cerebellar purkinje cells pcs can cause altered social behavior mice performed detailed transcriptional translational analyses tsc1deficient pcs understand molecular alterations cells found target transcripts fragile x mental retardation protein fmrp reduced mutant pcs evidence increased degradation surprisingly observed unchanged ribosomal binding many genes using translating ribosome affinity purification finally found multiple fmrp targets including shank2 reduced suggesting compensatory increases ribosomal binding efficiency may unable overcome reduced transcript levels data implicate dysfunction fmrp targets tsc suggest treatments aimed restoring function pathways may beneficialpmid34259631 doi107554 elife67399,0.0
ocrelizumab extended interval dosing multiple sclerosis times covid19 neurol neuroimmunol neuroinflamm 2021 jul 14 8 5 e1035 doi 101212 nxi0000000000001035 print 2021 sepabstractobjective evaluate clinical consequences extended interval dosing eid ocrelizumab relapsingremitting multiple sclerosis rrms coronavirus disease 2019 covid19 pandemicmethods retrospective multicenter cohort study compared patients rrms eid defined 4week delay dose interval control group standard interval dosing sid period january december 2020 results three hundred eighteen patients rrms longitudinally evaluated 5 german centers one hundred sixteen patients received ocrelizumab eid median delay interquartile range 868 5091307 weeks three months last ocrelizumab infusion 182 901 patients following sid 105 905 eid patients remained relapse free p 0903 threemonth confirmed progression disability observed 18 sid patients 89 11 eid patients 95 p 0433 mri progression documented 9 sid patients 45 8 eid patients 69 3month followup p 0232 multivariate logistic regression showed association treatment regimen evidence disease activity status followup 1266 95 ci 06952305 p 0441 clinical stability accompanied persistent peripheral cd19+ bcell depletion groups sid vs eid 826 vs 833 p 0463 disease activity cohort associated cd19+ bcell repopulationconclusion data support eid ocrelizumab potential risk mitigation strategy times covid19 pandemicclassification evidence study provides class iv evidence patients rrms eid least 4 weeks diminish effectiveness ocrelizumabpmid34261812 doi101212 nxi0000000000001035,0.0
palladiumcatalyzed #39 diarylation free alkenyl amines j chem soc 2021 jun 23 doi 101021 jacs1c04261 online ahead printabstractthe direct difunctionalization alkenes effective way construct multiple cc bonds onepot using single functional group regioselective dicarbofunctionalization alkenes therefore important area research rapidly obtain complex organic molecules herein report palladiumcatalyzed diarylation free alkenyl amines interrupted chain walking synthesis zselective alkenyl amines notably 1 3dicarbofunctionalization allyl groups well precedented present disclosure allows 1 3dicarbofunctionalization highly substituted allylamines give highly zselective trisubsubstituted olefin products cascade reaction operates via unprotected aminedirected mizorokiheck mh pathway featuring hydride elimination selectively chain walk furnish new terminal olefin generates cisselective alkenyl amines around sterically crowded allyl moiety operationally simple protocol applicable variety cyclic branched linear secondary tertiary alkenylamines broad substrate scope regard arene coupling partner well mechanistic studies performed help elucidate mechanism including presence likely unproductive side ch activation pathwaypmid34161068 doi101021 jacs1c04261,0.0
decreased expression clock gene bmal1 involved pathogenesis temporal lobe epilepsy abstractclock genes regulate circadian rhythm physiological activities also participate pathogenesis many diseases previous studies documented abnormal expression clock genes epilepsy however molecular mechanism brain muscle arntlike protein 1 bmal1 one core clock genes epileptogenesis seizures temporal lobe epilepsy tle remain unclear first investigated levels bmal1 clock proteins hippocampus subjects epilepsy define function bmal1 levels bmal1 decreased latent chronic phases experimental group compared control group knockout bmal1 hippocampal dentate gyrus dg neurons bmal1flox flox mice synapsin 1 syn1 promoter aav adenoassociated virus lowered threshold seizures induced pilocarpine administration highthroughput sequencing analysis showed pcdh19 protocadherin 19 gene associated epilepsy regulated bmal1 pcdh19 expression also decreased hippocampus epileptic mice furthermore higher levels bmal1 pcdh19 detected patients hippocampal sclerosis hs patients hs international league epilepsy ilae type iii altogether data suggest decreased expression clock gene bmal1 may participate epileptogenesis seizures via pcdh19 tle,0.0
humoral response sarscov2 covid19 vaccines patients multiple sclerosis treated immune reconstitution therapies abstractbackgroundit generally accepted people ms pwms vaccinated covid19 aim investigation evaluate humoral response natural sarscov2 infection two covid19 vaccines bnt162b2 pfizerbiontech beijing sinopharm bbibpcorv cohort pwms high efficacy disease modifying therapies dmts cladribine alemtuzumabmethodstwenty two pwms treated clinic neurology belgrade developed covid19 vaccinated sarscov2 treatment cladribine alemtuzumab included 18 patients treated cladribine 11 developed covid19 11 vaccinated sarscov2 four mrna vaccine 7 sinopharm four ms patients alemtuzumab vaccinated sarscov2 three mrna one sinopharm vaccine sarscov2 igg response measured using elisa antispike proteinbased serology inep belgrade serbia resultsall 7 patients cladribine treatment suffered covid19 developed igg antibodies 2055 months last symptoms four 100 patients cladribine vaccinated pfizerbiontech vaccine three seven 429 vaccinated sinopharm developed antibodies 4 patients alemtuzumab developed antibodies vaccination cases seroprotection occurred irrespective timing vaccination absolute lymphocyte countconclusionour findings small number highly active pwms lymphodepleting immune reconstitution therapies applied order successfully manage ms indicate number patients possible develop time seroprotection patients covid19 vaccination complex circumstances,0.0
sodium intensity changes differ relaxation densityweighted mri multiple sclerosis front neurol 2021 jul 14 12693447 doi 103389 fneur2021693447 ecollection 2021abstractintroduction source tissue sodium concentration tsc increase multiple sclerosis ms remains unclear attributed altered intracellular sodium concentration tissue microstructure paper investigates sodium ms using three new mri sequences methods three sodium scans acquired 47 t 30 patients 11 relapsingremitting 10 secondaryprogressive 9 primaryprogressive 9 healthy controls including densityweighted nadw short 30 excitation accurate tsc measurement projection acquisition coherent magnetization napacman designed enhanced relaxationbased contrast soft inversion recovery fluid attenuation nasirfla developed reduce fluid space contribution signal measured lesions n 397 normal appearing white matter nawm relative controls splenium corpus callosum anterior posterior limbs internal capsule correlations clinical cognitive evaluations tested ms patients results sodium intensity ms lesions elevated control wm greater amount napacman 75 nadw 35 latter representing tsc contrast nasirfla exhibited lower intensity region specific analysis scc 7 sodium intensity average ms nawm significantly different control wm either three scans nasirfla average nawm specifically posterior limb internal capsules positively correlated paced auditory serial addition test pasat discussion lower nasirfla signal lesions 2 greater napacman signal elevation control wm nadw can explained demyelination model also includes edema nawm demyelination model includes tissue atrophy suggests signal change nasirfla slightly greater nawm signal control wm nadw napacman reflecting experimental results models derived previous total myelin water fraction study ms t2relaxometry first time include sodium within myelin water space reduced auditory processing association lower signal nasirfla explained greater demyelination modeled impact three sodium mri sequences alternative explanations include intra extracellular sodium concentration change relaxationweighted sodium mri combination sodiumdensity mri may help elucidate microstructural metabolic changes mspmid34335450 pmcpmc8323606 doi103389 fneur2021693447,1.0
amyotrophic lateral sclerosis patients show increased peripheral intrathecal tcell activation brain commun 2021 jul 14 3 3 fcab157 doi 101093 braincomms fcab157 ecollection 2021abstractseveral studies suggest role peripheral immune system pathophysiology amyotrophic lateral sclerosis however comprehensive studies investigating intrathecal immune system amyotrophic lateral sclerosis rare elucidate whether compartmentspecific inflammation contributes amyotrophic lateral sclerosis pathophysiology investigated intrathecal peripheral immune profiles amyotrophic lateral sclerosis patients compared controls free neurological disorders controls patients dementia primary progressive multiple sclerosis routine csf parameters examined 308 patients including 132 amyotrophic lateral sclerosis patients subgroup 41 amyotrophic lateral sclerosis patients extensive flowcytometric immune cell profiling peripheral blood csf performed compared data 26 controls 25 dementia 21 multiple sclerosis patients amyotrophic lateral sclerosis patients presented significantly altered proportions monocyte subsets peripheral blood increased frequencies cd4+ cd8+ t cells expressing activation marker hladr peripheral blood cd8+ csf cd4+ cd8+ compared controls dementia multiple sclerosis patients exhibited comparable increase intrathecal cd8+ tcell activation cd8+ tcell activation peripheral blood amyotrophic lateral sclerosis higher multiple sclerosis patients furthermore intrathecal cd4+ tcell activation amyotrophic lateral sclerosis surpassed levels dementia patients intrathecal tcell activation resulted situ activation rather transmigration activated t cells blood tcell activation correlate amyotrophic lateral sclerosis progression patients rapid disease progression showed reduced intrathecal levels immuneregulatory cd56bright natural killer cells integration parameters composite score facilitated differentiation amyotrophic lateral sclerosis patients patients cohorts conclude alterations peripheral monocyte subsets well increased peripheral intrathecal activation cd4+ cd8+ t cells concomitant diminished immune regulation cd56bright natural killer cells suggest involvement immune cells amyotrophic lateral sclerosis pathophysiologypmid34405141 pmcpmc8363480 doi101093 braincomms fcab157,0.0
genomic mosaicism formed somatic variation aging diseased brain genes basel 2021 jul 14 12 7 1071 doi 103390 genes12071071abstractover past 20 years analyses single brain cell genomes revealed brain composed cells myriad distinct genomes brain genomic mosaic generated host dna sequencealtering processes occur somatically affect germline sequence changes heritable processes appear occur neurogenesis cells mitotic whereas others may also function postmitotic cells review multiple forms dna sequence alterations now documented aneuploidies aneusomies smaller copy number variations cnvs somatic repeat expansions retrotransposons genomic cdnas gencdnas associated somatic gene recombination sgr single nucleotide variations snvs catchall term dna content variation dcv also used describe overall phenomenon can include multiple forms within single cells genome requisite step analyses genomic mosaicism ongoing technology development also discussed genomic mosaicism alters one stable biological molecules dna may many repercussions ranging normal functions including effects aging creating dysfunction occurs neurodegenerative brain diseases show sporadic presentation unlinked causal heritable genespmid34356087 doi103390 genes12071071,0.0
robotassisted gait training patients multiple sclerosis randomized controlled crossover trial medicina kaunas 2021 jul 14 57 7 713 doi 103390 medicina57070713abstractbackground objectives gait disorders represent one disabling aspects multiple sclerosis ms strongly influence patient quality life improvement walking ability primary goal rehabilitation treatment aim study evaluate effectiveness robotassisted gait training ragt association physiotherapy treatment patients affected ms comparison ground conventional gait training study design randomized controlled crossover trial materials methods twentyseven participants affected ms edss scores 35 7 enrolled seventeen completed study received five training sessions per week five weeks conventional gait training experimental group without control group inclusion ragt patients prospectively evaluated first treatment session crossover phase second treatment session evaluation based 25foot walk test 25fw main outcome 6 min walk test 6mwt tinetti test modified ashworth scale modified motricity index lower limbs also measured disability parameters using functional independence measure quality life index instrumental kinematic gait parameters knee extensor strength doubletime support step length ratio 17 patients reached final evaluation results groups significantly improved gait parameters motor abilities autonomy recovery daily living activities generally better results ragt control treatment particular ragt group improved control group 25fw p 0004 6mwt p 0022 conclusions ragt valid treatment option association physiotherapy induce positive effects mscorrelated gait disorders results showed greater effectiveness recovering gait speed resistance conventional gait trainingpmid34356994 doi103390 medicina57070713,1.0
progress application drugs treatment multiple sclerosis front pharmacol 2021 jul 13 12724718 doi 103389 fphar2021724718 ecollection 2021abstractmultiple sclerosis ms autoimmune chronic inflammatory demyelinating disease central nervous system cns gives rise focal lesion cns cause physical disorders although environmental factors susceptibility genes reported play role pathogenesis ms etiology still remains unclear present complete cure drugs decelerate progression ms traditional therapies diseasemodifying drugs control disease severity ms drugs currently marketed mainly aim immune system however increasing attention paid development new treatment strategies targeting cns number neuroprotective drugs presently undergoing clinical trials may prove useful improvement neuronal function survival review summarized recent application drugs used ms treatment mainly introducing new drugs immunomodulatory neuroprotective regenerative properties possible treatment strategies ms additionally presented food drug administrationapproved ms treatment drugs administration methods mechanisms action safety effectiveness thereby evaluating treatment efficacypmid34326775 pmcpmc8313804 doi103389 fphar2021724718,1.0
focus allogeneic mesenchymal stromal cells versatile therapeutic tool treating multiple sclerosis abstractmultiple sclerosis ms central nervous system cns chronic illness autoimmune inflammatory neurodegenerative effects characterized neurological disorder axonal loss signs due myelin sheath autoimmune t cell attacks existing drugs including diseasemodifying drugs dmd help decrease intensity frequency ms attacks inflammatory conditions cns protection axonal damage improve axonal repair show side effects new therapeutic options required regard due neuroprotection properties immunomodulatory effects ability differentiate neurons transplantation mesenchymal stromal cells mscs can used ms therapy use adiposederived mscs admscs autologous bone marrow mscs bmscs demonstrated unexpected effects including invasive painful isolation method inadequate amounts bone marrow bm stem cells antiinflammatory impact reduction admscs isolated fat patients cell number differentiation potential decrease increase age bmscs donor researchers trying search alternate tissue sources mscs especially fetal annexes offer novel therapeutic choice ms therapy due limitation low cell yield invasive collection methods autologous mscs transplantation mscs ms treatment discussed review finally suggested allogeneic sources mscs appealing alternative autologous mscs hence potential novel solution ms therapy,1.0
csfresident cd4 + tcells display distinct gene expression profile relevance immune surveillance multiple sclerosis brain commun 2021 jul 13 3 3 fcab155 doi 101093 braincomms fcab155 ecollection 2021abstractthe cns traditionally considered immune privileged site now understood system immune surveillance predominantly involving cd4+ tcells identifying functional differences cns blood cd4+ tcells therefore relevance cns immune surveillance well neurological conditions multiple sclerosis cd4+ tcells play central role cd4+ tcells purified csf blood 21 patients newly diagnosed treatmentnave multiple sclerosis 20 individuals noninflammatory disorders using fluorescenceactivated cell sorting transcriptomes profiled rna sequencing paired comparisons cd4+ tcells csf blood identified 5156 differentially expressed genes controls 4263 differentially expressed multiple sclerosis patients false discovery rate 5 differential expression analysis cd4+ tcells collected csf highlighted genes involved migration activation cholesterol biosynthesis signalling including known relevance multiple sclerosis pathogenesis treatment expression markers cd4+ tcell subtypes suggested increased proportion th1 th17 cells csf gene ontology terms significant multiple sclerosis predominantly involved cellular proliferation twoway comparison csf versus blood cd4+ tcells multiple sclerosis compared noninflammatory disorder controls identified four significant genes false discovery rate 5 cyp51a1 lrrd1 yes1 pask implicating cholesterol biosynthesis migration mechanisms analysis csf cd4+ tcells extended cohort multiple sclerosis cases total n 41 compared noninflammatory disorder controls total n 38 identified 140 differentially expressed genes false discovery rate 5 many known relevance multiple sclerosis including xbp1 bhlhe40 cd40lg dpp4 itgb1 study provides largest transcriptomic analysis purified cell subpopulations csf date relevance understanding cns immune surveillance well multiple sclerosis pathogenesis treatment discoverypmid34761221 pmcpmc8574295 doi101093 braincomms fcab155,1.0
treatmentemergent adverse events occurring early treatment course cladribine tablets two phase 3 trials multiple sclerosis mult scler j exp transl clin 2021 jul 13 7 3 20552173211024298 doi 101177 20552173211024298 ecollection 2021 julsepabstractbackground treatmentemergent adverse events teaes occur close treatment initiation may negatively affect overall tolerability adherence important develop clear understanding potential early teaes initiating treatment cladribine tabletsobjective identify teaes begin early course treatment patients enrolled clarity oraclems studiesmethods post hoc analysis clarity oraclems safety populations assessed incidence teaes serious teaes drugrelated teaes teaes leading discontinuation patients receiving cladribine tablets placebo within 2 6 12 weeks treatment initiationresults week 12 613 patients treated cladribine tablets 35 mg kg 552 treated placebo experienced teae patients receiving cladribine tablets versus placebo experienced drugrelated teae week 12 347 vs 232 common teaes reported cladribine tablets headache 72 lymphopenia 68 nausea 60 patients receiving cladribine tablets placebo reported similar proportions serious teaes 22 vs 17 teaes leading treatment discontinuation 16 vs 14 conclusion cladribine tablets well tolerated first 12 weeks evidenced low incidence teaes leading treatment discontinuationpmid34345436 pmcpmc8283088 doi101177 20552173211024298,0.0
retrospective analysis changes lymphocyte levels patients multiple sclerosis tecfidera treatment mult scler j exp transl clin 2021 jul 13 7 3 20552173211029674 doi 101177 20552173211029674 ecollection 2021 julsepabstractbackground currently best practice recommendations lymphocyte subset monitoring patients multiple sclerosis pwms diseasemodifying therapies including tecfidera dimethyl fumarate dmf however several cases pwms dmf without severe lymphopenia high cd4cd8 t cell ratios went develop progressive multifocal leukoencephalopathyobjective objective characterize changes immune profile dmf treatment pwmsmethods retrospective analysis longitudinal data 299 pwms treated dmf fraser health multiple sclerosis clinic british columbia canada blood test results taken january 1 2013 april 1 2020results results suggest cd8+ t cells highest proportional decrease compared lymphocyte subset populations overall lymphocyte count response dmf treatment cd56+ natural killer cells similarly decreased response dmf treatment cd4cd8 t cell ratio measurement highest rate change response dmf initiation discontinuationconclusion cd8+ t cell count cd4cd8 t cell ratio may sensitive measurement immune landscape patients ms dmfpmid34345437 pmcpmc8283074 doi101177 20552173211029674,0.0
cognitive decline multiple sclerosis related progression retinal atrophy presence oligoclonal bands 5year followup study front neurol 2021 jul 13 12678735 doi 103389 fneur2021678735 ecollection 2021abstractbackground brain atrophy associated cognitive impairment retinal nerve fiber layer rnfl atrophy main biomarker neurodegeneration multiple sclerosis ms however data relationship inflammatory markers oligoclonal bands ocbs cerebrospinal fluid csf cognition rnfl atrophy brain atrophy scarce aim study assess influence rnfl thickness brain atrophy markers intrathecal ocbs immunoglobulin g igg index cognitive decline 5year period patients ms methods prospective singlecenter observational cohort study included 49 patients relapsing ms followed 5 years baseline patients underwent brain magnetic resonance imaging mri cognitive evaluation performed using brief international cognitive assessment ms bicams rnfl thickness assessed using optical coherence tomography oct ocbs igg levels csf evaluated baseline bicams oct mri findings reevaluated 5 years results significant reduction information processing speed visual learning temporal rnfl thickness huckman index third ventricle mean diameter found 49 patients relapsing ms observation period p 005 patients 633 positive ocbs 592 elevated igg indices atrophy temporal segment papillomacular bundle presence ocbs significantly related decline information processing speed patients p 005 however brain atrophy markers found significant general linear models conclusions rnfl atrophy presence ocbs related cognitive decline patients ms 5year followup period thereby suggesting utility potential biomarkers cognitive decline mspmid34326806 pmcpmc8315759 doi103389 fneur2021678735,0.0
skin sodium increased male patients multiple sclerosis related animal models proc natl acad sci u s 2021 jul 13 118 28 e2102549118 doi 101073 pnas2102549118abstractnovel mri techniques allow noninvasive quantification tissue sodium reveal skin prominent compartment sodium storage health disease since multiple sclerosis ms immunopathology initiated periphery increased sodium concentrations induce proinflammatory immune cells skin represents promising compartment linking high sodium concentrations ms immunopathology used 7t sodium mri 23namri inductively coupled plasma mass spectrometry investigate skin sodium content two mouse models ms additionally performed 3t 23namri calf skin muscles 29 male relapsingremitting ms rrms patients 29 matched healthy controls demographic clinical information collected interviews disease activity assessed expanded disability status scale scoring 23namri chemical analysis demonstrated significantly increased sodium content skin experimental autoimmune encephalomyelitis independent active immunization male patients rrms 23namri demonstrated higher sodium signal area skin compared age biological sexmatched healthy controls higher sodium predicting future disease activity cranial mri studies sodium enrichment specific skin found alterations sodium signals muscle tissues data add recently identified importance skin storage compartment sodium may represent important organ future investigations salt proinflammatory agent driving autoimmune neuroinflammation mspmid34260395 doi101073 pnas2102549118,0.0
internet search results correlate seasonal variation sarcoidosis background etiology pathophysiology sarcoidosis remains unclear epidemiologic studies limited relatively low prevalence internet prompted patients seek information medical diagnoses online google trends provides access anonymized version data new role epidemiology hypothesize seasonal variation relative search interest sarcoidosis suggest seasonal variation incidence sarcoidosismethodsgoogle trends used assess relative search volume 2010 2020 sarcoidosis sarcoid 7 countries anova multiple comparisons performed compare mean relative search volume month season country pvalue less 005 indicating statistical significanceresultsour analysis revealed significant seasonal variation search popularity 4 7 countries northern hemispheric countries combined direct comparison showed search terms popular spring specifically march april winter southern hemisphere data statistically significant showed trend towards nadir december peak september octoberconclusionsoverall findings suggest seasonal variation possible peak spring nadir winter supports hypothesis sarcoidosis seasonal variation commonly diagnosed spring evidence needed support well investigation pathophysiology sarcoidosis explain phenomenon,0.0
apostel 20 recommendations reporting quantitative optical coherence tomography studies neurology 2021 apr 28101212 wnl0000000000012125 doi 101212 wnl0000000000012125 online ahead printabstractobjective update consensus recommendations reporting quantitative optical coherence tomography oct study results thus revising previously published advised protocol oct study terminology elements apostel recommendationsmethods identify studies reporting quantitative oct results performed pubmed search terms quantitative optical coherence tomography 2015 2017 corresponding authors identified publications invited provide feedback initial apostel recommendations via online surveys following principle modified delphi method results evaluated discussed panel experts changes initial recommendations proposed final survey recirculated among corresponding authors obtain majority vote proposed changesresults one hundred sixteen authors participated surveys resulting 15 suggestions 12 finally accepted incorporated updated 9pointchecklist harmonized nomenclature outer retinal layers added exact area measurement description volume scans suggested reporting devicespecific features advised address potential bias manual segmentation manual correction segmentation errors references specific reporting guidelines room light conditions removed participants consensus recommendations increased 80 previous apostel version greater 90conclusions modified delphi method resulted expertled guideline evidence class iii grade criteria concerning study protocol acquisition device acquisition settings scanning protocol fundoscopic imaging postacquisition data selection postacquisition analysis nomenclature abbreviations statistical approach will still essential update recommendations new research practices regularlypmid33910937 doi101212 wnl0000000000012125,0.0
eliciting public preferences pharmaceutical subsidy iran discrete choice experiment study background deciding pharmaceutical subsidy regarded challenging issue healthcare policymakers iran times public preferences rarely attended iran invaluable including particular drug list subsidized medicationsobjectivesthe current study aims elicit public preferences develop evidencebased decisionmaking framework entering drug list subsidies iranmethodsdiscrete choice experiment dce employed elicit public preferences around 34 attributes identified based systematic review interview 51 experts holding expert panel 7 attributes finalized namely survival treatment quality life treatment qol alternative treatment age group target population cost burden government disease severity drug manufacturer country next 1224 households selected survey city tehran using random cluster sampling data analyzed using conditional logit modelresultsthe survival treatment 1245 se 0053 cost burden government 0140 se 0050 highest lowest priority respectively preferences allocating subsidy drug developed region unlike two regions level domestic drug production 0302 se 0073 inversely associated preferences toward allocating subsidy drug contrast districts living district number one 2053 se 0138 gave highest value promoting qol treatmentconclusionsit suggested policymakers pay attention attributes effectiveness alternative treatment developing evidencebased framework entering drug list subsidies study highlighted public belief governments subsidy medicines provided results increased survival qol,0.0
essential list medicinal products rare diseases recommendations irdirc rare disease treatment access working group background treatments often unavailable rare disease patients especially lowandmiddleincome countries reasons include lack financial support therapies onerous regulatory requirements approval drugs barriers include lack reimbursement administrative infrastructure knowledge diagnosis drug treatment options international rare diseases research consortium set rare disease treatment access working group first objective develop essential list medicinal products rare diseasesresultsthe working group extracted 204 drugs rare diseases fda ema databases chinas nmpa databases approval marketing authorization drugs organized seven disease categories metabolic neurologic hematologic antiinflammatory endocrine pulmonary immunologic plus miscellaneous categoryconclusionsthe proposed list essential medicinal products rare diseases intended initiate discussion collaboration among patient advocacy groups health care providers industry government agencies enhance access appropriate medicines rare disease patients throughout world,0.0
covid19 children expressions type ii iii interferons trim28 setdb1 endogenous retroviruses mild severe cases int j mol sci 2021 jul 13 22 14 7481 doi 103390 ijms22147481abstractchildren new coronavirus disease 2019 covid19 milder symptoms better prognosis adult patients several investigations assessed type ii iii interferon ifn signatures sarscov2 infected adults however data available pediatric patients trim28 setdb1 regulate transcription multiple genes involved immune response well human endogenous retroviruses hervs exogenous viral infections can trigger activation hervs turn can induce inflammatory immune reactions despite potential crosstalks sarscov2 infection trim28 setdb1 hervs information expressions covid19 patients lacking assessed pcr real time taqman amplification assay transcription levels six ifni stimulated genes ifnii three sensitive genes three ifnliis well trim28 setdb1 pol genes hervh k w families env genes syncytin syn 1 syn2 multiple sclerosisassociated retrovirus mrsv peripheral blood covid19 children control uninfected subjects higher expression levels ifni ifnii inducible genes observed 36 covid19 children mild moderate disease compared uninfected controls whereas concentrations decreased 17 children severe disease 11 multisystem inflammatory syndrome misc similar findings found expression trim28 setdb1 every herv gene positive correlations emerged transcriptional levels type ii ifns trim28 setdb1 hervs covid19 patients ifniii expressions comparable group subjects preserved induction ifns contribute better control infection children compared adults ifniii deficiency reported upregulation ifni ifnii trim28 setdb1 hervs children mild symptoms declines severe cases misc positive correlations transcription sarscov2infected children suggest may play important roles conditioning evolution infectionpmid34299101 doi103390 ijms22147481,0.0
burden neurological disorders across states india global burden disease study 19902019 summarybackgrounda systematic understanding burden neurological disorders subnational level readily available india present comprehensive analysis disease burden trends neurological disorders state level indiamethodsusing accessible data multiple sources estimated prevalence incidence disabilityadjusted lifeyears dalys neurological disorders 1990 2019 states india part global burden diseases injuries risk factors study 2019 assessed contribution neurological disorder deaths dalys india 2019 trends prevalence incidence daly rates time heterogeneity states india also assessed pearson correlation coefficient sociodemographic index sdi states prevalence incidence daly rates neurological disorder additionally estimated contribution known risk factors dalys neurological disorders calculated 95 uncertainty intervals uis mean estimatesfindingsthe contribution noncommunicable neurological disorders total dalys india doubled 40 95 ui 3250 1990 82 66102 2019 contribution injuryrelated neurological disorders increased 02 0203 06 0507 conversely contribution communicable neurological disorders decreased 41 3548 11 0915 period 2019 largest contributors total neurological disorder dalys india stroke 379 299461 headache disorders 175 36325 epilepsy 113 90143 cerebral palsy 57 4277 encephalitis 53 3789 crude daly rate several neurological disorders considerable heterogeneity states 2019 highest variation tetanus 932 times meningitis 83 times stroke 55 times sdi states moderate significant negative correlation communicable neurological disorder daly rate moderate significant positive correlation injuryrelated neurological disorder daly rate 2019 noncommunicable neurological disorders increase prevalence incidence 1990 2019 substantial decreases evident incidence daly rates communicable neurological disorders period migraine multiple sclerosis prevalent among females males traumatic brain injuries common among males females 2019 communicable diseases contributed majority total neurological disorder dalys children younger 5 years noncommunicable neurological disorders highest contributor age groups 2019 leading risk factors contributing dalys due noncommunicable neurological disorders india included high systolic blood pressure air pollution dietary risks high fasting plasma glucose high bodymass index communicable disorders identified risk factors modest contributions dalys low birthweight short gestation air pollutioninterpretationthe increasing contribution noncommunicable injuryrelated neurological disorders overall disease burden india substantial statelevel variation burden many neurological disorders highlight need statespecific health system responses address gaps neurology services related awareness early identification treatment rehabilitationfundingbill melinda gates foundation indian council medical research department health research ministry health family welfare government india,0.0
drugs avoid improve quality use medicines australia faring background year french independent bulletin prescrire publishes list medicines drugs avoid used clinical practice risktobenefit ratio unfavourable study assessed market approval reimbursement use medicines australiamethodsthe approval status medicines included 2019 prescrire drugs avoid list assessed searching australian register therapeutic goods website funding status assessed pharmaceutical benefits scheme pbs website australian public insurance system use levels determined examining governmental reports prescribing rates including australian statistics medicines asm reports drug use reports released drug utilisation sub committee dusc pbs statisticsresultsof 93 medicines included prescrire 2019 drug avoid list included 57 61 approved australia 2019 including 9 16 sold overthecounter medicines 35 38 listed pbs 22 24 registered listed pbs although medicines used infrequently 16 46 substantial use despite serious safety concerns dipeptidyl peptidase4 dpp4 inhibitors used 22 patients receiving treatment diabetes 2016 50 000 patients received antidementia medicine 2014 19 increase since 2009 denosumab became 8th medicine terms total sales funded australian government 20172018conclusionsprescrires assessments provide reliable external benchmark assess current use medicines australia sixteen drugs avoid judged harmful beneficial based systematic independent evidence reviews substantial use australia results raise serious concerns awareness australian clinicians medicine safety efficacy medicines safety become australian national health priority regulatory reimbursement agencies review marketing funding status medicines shown provide efficacy safety least similar alternative therapeutic options,0.0
current status etiology valvular heart disease china populationbased survey background epidemiology valvular heart disease vhd changed markedly last 50 years worldwide prevalence features vhd china unknown objective study investigate current status etiology vhd chinamethodswe used crosssectional national survey stratified multistage random sampling general chinese population estimate vhd burden data demographic characteristics medical history physical examination blood tests potential etiology collected echocardiography used detect vhdresultsthe national survey enrolled 34 994 people aged 35 years older across china overall 31 499 people included final analysis 1309 participants diagnosed vhd weighted prevalence 38 estimated 25 million patients china prevalence vhd increased age higher participants hypertension chronic kidney disease counterparts among participants vhd 551 rheumatic 213 degenerative proportion rheumatic decreased age proportion degenerative rose age however prevalence rheumatic disease still higher elderly population younger population logistic regression revealed age hypertension correlated vhdconclusionsin china rheumatic heart disease still major cause vhd significant increase degenerative heart disease age hypertension important easily identifiable markers vhd,0.0
white matter hyperintensities autopsyconfirmed frontotemporal lobar degeneration alzheimers disease background aimed systematically describe burden distribution white matter hyperintensities wmh investigate correlations neuropsychiatric symptoms pathologically proven alzheimers disease ad frontotemporal lobar degeneration ftld methodsautopsyconfirmed cases identified sunnybrook dementia study including 15 cases ad 58 cases ftld 22 ftldtdp cases 10 ftldtau picks cases 11 ftldtau corticobasal degeneration cases 15 ftldtau progressive supranuclear palsy cases healthy matched controls n 35 included comparison purposes data analyses included ancova compare burden wmh antemortem brain mri groups adjusted linear regression models identify associations wmh burden neuropsychiatric symptoms imageguided pathology review selected areas wmh pathologic groupresultsburden regional distribution wmh differed significantly neuropathological groups f5 77 267 p 0029 ftldtdp group highest mean volume globally 8032 8889 mm3 frontal regions 4897 6163 mm3 ad group highest mean volume occipital regions 468 420 mm3 total score neuropsychiatric inventory correlated bilateral frontal wmh volume 0330 p 0006 depression correlated bilateral occipital wmh volume 0401 p 0001 apathy correlated bilateral frontal wmh volume 0311 p 0009 corrected false discovery rate imageguided neuropathological assessment selected cases highest burden wmh pathologic group revealed presence severe gliosis myelin pallor axonal loss distinguishing features indicative underlying proteinopathyconclusionsthese findings suggest wmh associated neuropsychiatric manifestations ad ftld wmh burden regional distribution neurodegenerative disorders differ according underlying neuropathological processes,1.0
signals pseudostarvation unveil amino acid transporter slc7a11 key determinant control treg cell proliferative potential immunity 2021 may 11s10747613 21 00176x doi 101016 jimmuni202104014 online ahead printabstracthuman cd4+cd25hifoxp3+ regulatory t treg cells key players control immunological selftolerance homeostasis report signals pseudostarvation reversed human treg cell vitro anergy integrated transcriptional response pertaining proliferation metabolism transmembrane solute carrier transport molecular level treg cell proliferative response dependent induction cystine glutamate antiporter solute carrier slc 7a11 whose expression controlled nuclear factor erythroid 2related factor 2 nrf2 slc7a11 induction treg cells impaired subjects relapsingremitting multiple sclerosis rrms autoimmune disorder associated reduced treg cell proliferative capacity treatment rrms subjects dimethyl fumarate dmf rescued slc7a11 induction fully recovered treg cell expansion results suggest previously unrecognized mechanism may account progressive loss treg cells autoimmunity unveil slc7a11 major target rescue treg cell proliferationpmid34004141 doi101016 jimmuni202104014,0.0
nutritional status multiple sclerosis ms patients attending kasr alainy ms unit exploratory crosssectional study j egypt public health assoc 2021 jul 13 96 1 20 doi 101186 s42506021000803abstractbackground nutrition claimed factor ms causation course complications management several studies conducted assess nutritional status ms patients however studies conducted assess problem egypt therefore purpose current study assess nutritional status sample ms patientsmethods researchers conducted exploratory crosssectional study among 76 relapsingremitting ms rrms patients attending kasr alainy multiple sclerosis unit kamsu october 2018 january 2019 assess nutritional status sample ms patients data collected using structured interview questionnaire including inquiry socioeconomic status nutritional status using anthropometric measurements patientgenerated subjective global assessment pgsga semiquantitative food frequency questionnaires sqffq hemoglobin level measurement assessment fatigue done using modified fatigue impact scale 5items versionresults mean age study participants 30 6 years disease duration ranged 2 264 months malnutrition prevalent among 671 276 overweight 368 obese 26 underweight half investigated patients anemic according pgsga half studied patients 539 classified moderately suspected malnourished unhealthy dietary habits taking meals junk food intake skipping breakfast observed considerable proportions group sqffq revealed overconsumption energy fat less acceptable consumption dietary fibers studied patientsconclusions overweight obesity anemia unhealthy dietary habits prevalent among rrms patients attending kamsu nutrition care service extremely needed group patientspmid34255211 doi101186 s42506021000803,0.0
peritoneal dialysis guidelines 2019 part 1 position paper japanese society dialysis therapy abstractapproximately 10 years passed since peritoneal dialysis guidelines formulated 2009 much evidence reported succeeding years taken consideration previous guidelines eg next peritoneal dialysis pd trial encapsulating peritoneal sclerosis eps japan significance angiotensinconverting enzyme inhibitors aceis angiotensin receptor blockers arbs effects icodextrin solution new developments peritoneal pathology new international recommendation proposal exitsite management essential incorporate new developments new clinical practice guidelines meanwhile process creating guidelines changed dramatically worldwide differs process creating clinical practice guides revision conducted systematic reviews using global standard methods also decided adopt twopart structure create reference tool used widely societys members attending variety patients working group consensus decided part 1 present conventional descriptions part 2 pose clinical questions cqs systematic review format thus part 1 vastly covers pd satisfy requirements members japanese society dialysis therapy jsdt article duplicated publication japanese version guidelines reproduced permission jsdt,0.0
deep spatial profiling human covid19 brains reveals neuroinflammation distinct microanatomical microgliatcell interactions immunity 2021 jun 9s10747613 21 002466 doi 101016 jimmuni202106002 online ahead printabstractcovid19 can cause severe neurological symptoms underlying pathophysiological mechanisms unclear interrogated brain stems olfactory bulbs postmortem patients covid19 using imaging mass cytometry understand local immune response spatially resolved highdimensional singlecell level compared immune map noncovid respiratory failure multiple sclerosis control patients observed substantial immune activation central nervous system pronounced neuropathology astrocytosis axonal damage bloodbrainbarrier leakage detected viral antigen ace2receptorpositive cells enriched vascular compartment microglial nodules perivascular compartment represented covid19specific microanatomicimmune niches contextspecific cellular interactions enriched activated cd8+ t cells altered brain tcellmicroglial interactions linked clinical measures systemic inflammation disturbed hemostasis study identifies profound neuroinflammation activation innate adaptive immune cells correlates covid19 neuropathology implications potential therapeutic strategiespmid34174183 doi101016 jimmuni202106002,0.0
spns2 enables tcell egress lymph nodes immune response cell rep 2021 jul 13 36 2 109368 doi 101016 jcelrep2021109368abstractt cell expression sphingosine 1phosphate s1p receptor 1 s1pr1 enables t cell exit lymph nodes lns lymph endothelial s1pr1 expression regulates vascular permeability drugs targeting s1pr1 treat autoimmune disease trapping pathogenic t cells within lns adverse cardiovascular side effects homeostasis transporter spns2 supplies lymph s1p enables t cell exit transporter mfsd2b supplies blood s1p supports vascular function unknown whether spns2 remains necessary supply lymph s1p immune response whether inflammation compensatory transporters upregulated using model dermal inflammation demonstrate spns2 supplies s1p guides t cells lns ongoing immune response furthermore deletion spns2 protective mouse model multiple sclerosis results support therapeutic potential spns2 inhibitors achieve spatially specific modulation s1p signalingpmid34260944 doi101016 jcelrep2021109368,0.0
coinfection sarscov2 mtb miss wood trees bmj case rep 2021 jul 13 14 7 e240581 doi 101136 bcr2020240581abstractscarce data exist coinfection sarscov2 mycobacterium tuberculosis mtb young woman undergoing treatment multiple sclerosis brought hospital covid19 positive status evaluation chest xray showed right upper midzone opacity lead suspicion mtb sputum came positive acidfast bacilli afb staining cartridgebased nucleic acid amplification test cbnaat confirmed rifampicin resistance detected started antitubercular regimen discharged end intensive phase treatment symptoms subsided sputum cbnaat still showed presence tb bacilluspmid34257109 doi101136 bcr2020240581,0.0
vitamin d blood parameters biomolecules 2021 jul 12 11 7 1017 doi 103390 biom11071017abstractbackground vitamin d steroid anabolicresembling chemical structure vitamin d essential many processes human body hydroxylationaims study investigate impact 25hydroxyvitamin d plasma concentrations blood parameters number erythrocytes hematocrit mean corpuscular hemoglobin mean corpuscular volumemethods serial assessments done 290 patients multiple sclerosis repeated mean interval 245 days recommendation vitamin d supplementation given case concentration lower 20 ng ml combined prescription formulation containing vitamin d vitamin kresults fall vitamin d 119 subjects rise 164 change appeared 7 participants vitamin d values went assessments moments computed increase mean corpuscular haemoglobin significantly lower compared rise mean corpuscular haemoglobin associated vitamin d elevation vitamin d declined computed fall mean corpuscular volume fall significantly lower compared decrease mean corpuscular volume vitamin d rose positive correlations found differences vitamin d mean corpuscular haemoglobin respectively mean corpuscular volume inverse relations appeared disparities vitamin d erythrocytes respectively haematocritconclusions elevation vitamin d plasma levels provides enhanced preconditions better tissue oxygenation cellular levelpmid34356641 doi103390 biom11071017,0.0
role bdnf nmdarinduced lysosomal recruitment mtorc1 regulation neuronal mtorc1 activity abstractmemory long term potentiation require de novo protein synthesis key regulator process mtorc1 complex comprising mtor kinase growth factors activate mtorc1 via pathway involving pi3kinase akt tsc complex gtpase rheb nonneuronal cells translocation mtorc1 late endocytic compartments les rheb enriched triggered amino acids however regulation mtorc1 neurons remains unclear mouse hippocampal neurons observed bdnf treatments activating nmda receptors trigger robust increase mtorc1 activity nmda receptors activation induced significant recruitment mtor onto lysosomes even absence external amino acids whereas mtorc1 evenly distributed neurons resting conditions nmda receptorinduced mtor translocation les partly dependent bdnf receptor trkb suggesting bdnf contributes effect nmda receptors mtorc1 translocation addition combination rheb overexpression artificial mtorc1 targeting les means modified component mtorc1 fused letargeting motif strongly activated mtor gain spatial temporal control mtor localization designed optogenetic module based lightsensitive dimerizers able recruit mtor les cells expressing optogenetic tool mtor translocated les upon photoactivation absence growth factor sufficient activate mtorc1 contrast mtorc1 potently activated combination bdnf photoactivation data demonstrate two important triggers synaptic plasticity bdnf nmda receptors synergistically power two arms mtorc1 activation mechanism ie mtorc1 translocation les rheb activation moreover unmask functional link nmda receptors mtorc1 underlie changes synaptic proteome associated longlasting changes synaptic strength,0.0
switching antifibrotics patients idiopathic pulmonary fibrosis multicenter retrospective cohort study background currently two antifibrotics used treat idiopathic pulmonary fibrosis ipf pirfenidone nintedanib antifibrotics slow disease progression reducing annual decline forced vital capacity fvc possibly improves outcomes ipf patients treatment patients occasionally switch antifibrotic treatments however prognostic implication changing antifibrotics yet evaluatedmethodsthis multicenter retrospective cohort study examined 262 consecutive ipf patients received antifibrotic therapy antifibrotic agents switched 37 patients 141 prognoses compared patient cohort switched antifibrotics switchipf without nonswitchipf using propensityscore matched analysesresultsthe median period initiation antifibrotic therapy drug switch 258 127353 months common reasons switch disease progression n 17 followed gastrointestinal disorders n 12 37 patients switched antifibrotics eight patients disrupted switched antifibrotics adverse reactions overall prognosis switchipf cohort significantly better nonswitchipf cohort median periods 672 vs 271 months p 00001 propensityscore matched analyses adjusted age sex fvc history acute exacerbation usage longterm oxygen therapy switchipf cohort significantly longer survival times nonswitchipf group median 672 vs 413 months p 00219 secondline antifibrotic therapy showed similar survival probabilities firstline antifibrotic therapy multistate model analysesconclusionswitching antifibrotics feasible may improve prognosis patients ipf prospective study will required confirm clinical implication switching antifibrotics,0.0
factors associated physical psychological social frailty among communitydwelling older persons europe crosssectional study urban health centres europe uhce background frailty agerelated condition resulting state increased vulnerability regarding functioning across multiple systems multidimensional concept referring physical psychological social domains purpose study identify factors demographic characteristics lifestyle factors health indicators associated overall frailty physical psychological social frailty communitydwelling older people five european countriesmethodsthis crosssectional study used baseline data 2289 participants urban health center european project five european countries multivariable logistic regression models used assess associations factors overall frailty three frailty domainsresultsthe mean age 797 sd 57 participants older female secondary equivalent education lived alone risk alcohol use less physically active multimorbidity malnourished higher level medication risk higher odds overall frailty p 005 age associated psychological social frailty sex associated social frailty smoking migration background associated overall frailty domains existed interaction effect sex household composition regarding social frailty p 00003 conclusionsthe present study contributed new insights risk factors frailty three domains physical psychological social frailty nurses physicians public health professionals policymakers aware risk factors type frailty furthermore examine risk factors comprehensively consider overall frailty well three domains order contribute decisionmaking precisely prevention management frailtytrial registrationthe intervention uhce project registered isrctn registry isrctn52788952 date registration 13 03 2017,0.0
antinmethyldaspartate receptor encephalitis presenting atypical psychosis multiple sclerosis case report background antinmethyldaspartate receptor antinmdar encephalitis autoimmune disorder often presents neuropsychiatric symptoms large proportion cases associated identifiable tumor commonly ovarian teratoma however recent literature also described overlap antinmdar encephalitis demyelinating syndromes cases reported antinmdar encephalitis patients adem optic neuritis myelitis multiple sclerosis link considered rare however important clinical implications treatments prognosis may differcase presentationa 33yearold female history multiple sclerosis presented newonset neuropsychiatric symptoms substanceinduced psychosis ruled admitted medical ward work psychosis secondary multiple sclerosis however consultationliaison psychiatry service noted atypical symptoms concerning autoimmune encephalitis admission psychiatric inpatient ward deferred antinmdar encephalitis diagnosed csf analysis demonstrating lymphocytic pleocytosis antinmdar antibodies addition firstline treatment encephalitis steroids secondline immunotherapies also implemented given patients underlining demyelinating syndrome patients neurologic psychiatric symptoms began improveconclusionsthere literature demonstrate possible connection antinmdar encephalitis demyelinating syndromes autoimmune encephalitis considered patients multiple sclerosis presenting atypical symptoms determining correct diagnosis crucial inform appropriate treatment protocol improve prognosis,1.0
multiple sclerosis peru national prevalence study using capturerecapture analysis abstractbackgroundthere scarce epidemiological data multiple sclerosis ms latin america national epidemiological studies needed guide health policy related msobjectiveto determine ms national prevalence peru describe clinical epidemiological characteristics diseasemethodswe conducted crosssectional prevalence study perunulls four largest regions using two sources included adult patients diagnosed ms neurologist using mcdonald criteria performed capturerecapture analysis using nearly unbiased estimator model calculated prevalence proportion adult peruvian population 2016 additionally summarized patients epidemiological clinical characteristicsresultswe identified 417 cases 135 first source 282 one found point prevalence 912 cases per 100 000 inhabitants 95 ci 56 126 age range 35 45 yearsold 519 female common type ms relapsingremitting 793 frequent treatment subcutaneous ifn1b 407 conclusionperu medium ms prevalence compared latin american countries lima region highest number cases similar clinical characteristics countries region,0.0
robotassisted total gastrectomy gastric cancer patient amyotrophic lateral sclerosis receiving longterm tracheostomy invasive ventilation int cancer conf j 2021 jul 12 10 4 318323 doi 101007 s13691021004997 ecollection 2021 octabstractamyotrophic lateral sclerosis als fatal neurodegenerative disease although affected patients may develop cancers major surgical intervention hampered questionable overall benefit due limited prognosis risk postoperative respiratory collapse recent study however showed tracheostomy invasive ventilation tiv prolonged median survival 113 years thus patients als receiving tiv might benefit major surgery 66yearold man als received tiv enteral tube feeding 8 years presented bloody stool patient also type 2 diabetes mellitus stage 4 chronic kidney disease abdominal aortic aneurysm antiphospholipid syndrome well multiple episodes pneumonia catheterrelated urinary tract infection treated antibiotics medical examination esophagogastroduodenoscopy revealed type 3 tumor middle part stomach patients preoperative diagnosis gastric cancer gc mu type3 lesspost t3 ss n1 h0 p0 m0 cstage iii estimated mortality rate 305 according japanese national clinical database patient family fully informed risk surgery patient clearly requested curative surgery eye movement thus robotassisted total gastrectomy ratg performed tissues extremely fragile hemorrhagic surgical time 7 h 0 min intraoperative blood loss 324 ml pathological examination revealed gc mu type3 t4a se n2 h0 cy0 p0 m0 fstage iiib postoperative course uneventful remained stable condition 3 months findings suggest patients als achieve longer survival tiv can undergo major cancer surgery including robotassisted surgery may facilitate better midlongterm prognosissupplementary information online version contains supplementary material available 101007 s13691021004997pmid34567945 pmcpmc8421503 doi101007 s13691021004997,0.0
identification immunological changes appearing csf early immunosenescence process occurring multiple sclerosis front immunol 2021 jul 12 12685139 doi 103389 fimmu2021685139 ecollection 2021abstractpatients multiple sclerosis ms suffer age early immunosenescence process influence treatment response increase risk infections explored whether lipidspecific oligoclonal igm bands lsocmb associated highly inflammatory ms modify immunological profile induced age ms crosssectional study included 263 ms patients classified according presence m+ n72 absence m n191 lsocmb csf cellular subsets molecules implicated immunosenescence explored m patients aging induced remarkable decreases absolute csf counts cd4+ cd8+ t lymphocytes including th1 th17 cells b cells including secreting tnfalpha also increased serum anticmv igg antibody titers indicative immunosenescence csf chi3l1 levels related astrocyte activation contrast m+ patients showed ageassociated increase tim3 biomarker t cell exhaustion increased values chi3l1 independently age finally groups age induced increase csf levels pdl1 inductor t cell tolerance activin part senescenceassociated secretome related inflammaging changes independent disease duration finally resulted augmented disability summary ms patients experience age modest induction tcell tolerance activation innate immunity resulting increased disability additionally m patients show clear decreases csf lymphocyte numbers increase risk infections thus age immunological status important tailoring effective therapies mspmid34322119 pmcpmc8311928 doi103389 fimmu2021685139,0.0
characterization microglial transcriptomes brain spinal cord mice early late experimental autoimmune encephalomyelitis using ribotag strategy sci rep 2021 jul 12 11 1 14319 doi 101038 s41598021935901abstractmicroglia play important role pathogenesis multiple sclerosis mouse model ms experimental autoimmune encephalomyelitis eae fully understand role microglia eae characterized microglial transcriptomes onset motor symptoms preonset symptomatic eae compared transcriptome brain behavioral changes initiated spinal cord damage revealed motor sensory deficits used ribotag strategy characterize ribosomebound mrna microglia without incurring possible transcriptional changes cell isolation brain spinal cord samples clustered separately stages eae indicating regional heterogeneity differences gene expression observed brain spinal cord preonset symptomatic animals profound effects spinal cord symptomatic animals canonical pathway analysis revealed changes neuroinflammatory pathways immune functions enhanced cell division preonset symptomatic brain spinal cord also observed continuum many pathways preonset stage continue symptomatic stage eae results provide additional evidence regional temporal heterogeneity microglial gene expression patterns may help understanding mechanisms underlying various symptomology mspmid34253764 doi101038 s41598021935901,0.0
interpretable deep learning remote characterisation ambulation multiple sclerosis using smartphones sci rep 2021 jul 12 11 1 14301 doi 101038 s4159802192776xabstractthe emergence digital technologies smartphones healthcare applications demonstrated possibility developing rich continuous objective measures multiple sclerosis ms disability can administered remotely outofclinic deep convolutional neural networks dcnn may capture richer representation healthy msrelated ambulatory characteristics raw smartphonebased inertial sensor data standard featurebased methodologies overcome typical limitations associated remotely generated health data low subject numbers sparsity heterogeneous data transfer learning tl model similar large opensource datasets proposed tl framework leveraged ambulatory information learned human activity recognition har tasks collected wearable smartphone sensor data demonstrated finetuning tl dcnn har models towards ms disease recognition tasks outperformed previous support vector machine svm featurebased methods well dcnn models trained endtoend upwards 815 lack transparency blackbox deep networks remains one largest stumbling blocks wider acceptance deep learning clinical applications ensuing work therefore aimed visualise dcnn decisions attributed relevance heatmaps using layerwise relevance propagation lrp lrp framework patterns captured smartphonebased inertial sensor data reflective healthy versus people ms pwms begin established understood interpretations suggested cadencebased measures gait speed ambulationrelated signal perturbations distinct characteristics distinguished ms disability healthy participants robust interpretable outcomes generated highfrequency outofclinic assessments greatly augment current inclinic assessment picture pwms inform better disease management techniques enable development better therapeutic interventionspmid34253769 doi101038 s4159802192776x,0.0
oral administration methylprednisolone powder intravenous injection dissolved water treat ms nmosd relapses covid19 pandemic realworld setting abstractbackgroundupon covid19 pandemic emergence safety concerns logistic drawbacks stimulated search alternatives pulse therapy infusion centres treat multiple sclerosis relapsesobjectiveto describe experience treating multiple sclerosis relapses dilute injectable methylprednisolone powder orally administered safe homebased environment totally virtual assessment follow via telemedicinemethodsdescriptive observational retrospective singlecentre open label study realworld settingresultsbetween august 2020 march 2021 ten multiple sclerosis patients one neuromyelitis optica spectrum disease patient regularly assisted multiple sclerosis centre argentina experienced twelve disease relapses nine moderate severe relapses three mild relapses treated oral dilute injectable methylprednisolone powder pulses good efficacy well adequate tolerance safety profileconclusionsthe oral pulse therapy based methylprednisolone powder dilution describe simple comfortable administer can option countries like argentina oral methylprednisolone formulation marketed pandemic times home based virtually monitored pulse therapy represent safe effective alternative manage relapses minimizing patientnulls risk exposure sarscov2,1.0
paradigm shift cellfree approach emerging role mscsderived exosomes regenerative medicine abstractrecently mesenchymal stem stromal cells mscs due proangiogenic antiapoptotic immunoregulatory competencies along fewer ethical issues presented rational strategy regenerative medicine current reports signified pleiotropic effects mscs related differentiation potentials rather exerted release soluble paracrine molecules nanosized nontoxic biocompatible barely immunogenic owning targeting capability organotropism exosomes considered nanocarriers possible use diagnosis therapy exosomes convey functional molecules long noncoding rnas lncrnas micrornas mirnas proteins eg chemokine cytokine lipids mscs target cells participate intercellular interaction procedures enable repair damaged diseased tissues organs findings evidenced exosomes alone liable beneficial influences mscs myriad experimental models suggesting msc exosomes can utilized establish novel cellfree therapeutic strategy treatment varied human disorders encompassing myocardial infarction mi cnsrelated disorders musculoskeletal disorders eg arthritis kidney diseases liver diseases lung diseases well cutaneous wounds importantly compared mscs msc exosomes serve steady entities reduced safety risks concerning injection live cells microvasculature occlusion risk current review will discuss therapeutic potential msc exosomes innovative approach context regenerative medicine highlight recent knowledge msc exosomes translational medicine focusing vivo researches,1.0
development web deployment automated neuroradiology mri protocoling tool natural language processing background systematic approach mri protocol assignment essential efficient delivery safe patient care advances natural language processing nlp allow development accurate automated protocol assignment aim develop evaluate deploy nlp model automates protocol assignment given clinician indication textmethodswe collected 7139 spine mri protocols routine contrast 990 head mri protocols routine brain contrast brain single institution protocols split training n 4997 spine mri n 839 head mri validation n 1071 spine mri fivefold crossvalidation used head mri test n 1071 spine mri n 151 head mri sets fasttext xgboost used develop 2 nlp models classify spine head mri protocols respectively flaskbased web app developed deployed via herokuresultsthe spine mri model accuracy 8338 receiver operator characteristic area curve rocauc 08873 head mri model accuracy 8543 routine brain protocol rocauc 09463 contrast brain protocol rocauc 09284 cancer infectious inflammatory related keywords associated contrast administration structural anatomic abnormalities stroke altered mental status indicative routine spine brain mri respectively error analysis revealed increasing sample size may improve performance head mri protocols web version model provided demonstration deploymentconclusionwe developed webdeployed two nlp models accurately predict spine head mri protocol assignment improve radiology workflow efficiency,0.0
inhibition mtorc1 atf4induced redd1 sestrin2 expression metformin background although major anticancer effect metformin involves ampkdependent ampkindependent mtorc1 inhibition mechanisms action still fully understoodmethodsto investigate molecular mechanisms underlying effect metformin mtorc1 inhibition mtt assay rtpcr western blot analysis performedresultsmetformin induced expression atf4 redd1 sestrin2 concomitant inhibition mtorc1 activity treatment redd1 sestrin2 sirna reversed mtorc1 inhibition induced metformin indicating redd1 sestrin2 important inhibition mtorc1 triggered metformin treatment moreover redd1 sestrin2mediated mtorc1 inhibition response metformin independent ampk activation additionally lapatinib enhances cell sensitivity metformin knockdown redd1 sestrin2 decreased cell sensitivity metformin lapatinibconclusionsatf4induced redd1 sestrin2 expression response metformin plays important role mtorc1 inhibition independent ampk activation signalling pathway therapeutic value,0.0
hml6 endogenous retrovirus chromosome 3 upregulated amyotrophic lateral sclerosis motor cortex sci rep 2021 jul 12 11 1 14283 doi 101038 s41598021937423abstractthere increasing evidence endogenous retroviruses ervs play significant role central nervous system diseases including amyotrophic lateral sclerosis als studies als consistently identified retroviral enzyme reverse transcriptase activity patients evidence indicates ervs cause reverse transcriptase activity als currently unclear whether due specific erv locus family ervs employed combination bioinformatic methods identify whether specific ervs erv families associated als using largest postmortem rnasequence datasets available selectively identified ervs closely resembled fulllength proviruses discovery dataset one erv locus hml6_3p2131c showed significant increased expression postmortem motor cortex tissue multipletesting correction using six replication postmortem datasets found hml6_3p2131c consistently upregulated als motor cortex cerebellum tissue addition hml6_3p2131c showed significant coexpression cytokine binding genes involved ebv htlv1 hiv type1 infections significant differences erv family expression als controls results support hypothesis specific erv loci involved als pathologypmid34253796 doi101038 s41598021937423,0.0
brain volume change highdose immunosuppression autologous hematopoietic cell transplantation relapsingremitting multiple sclerosis abstractbackgroundbrain volume loss bvl commonly observed highdose immunosuppression autologous hematopoietic cell transplantation hdit hct treatment multiple sclerosis ms better understand mechanisms underlying bvl associated treatment characterized time courses wholebrain wb greymatter gm whitematter wm volume loss relapsingremitting ms rrms patients received beambased hdit hctmethodswe used jacobian integration measure mribased wb gm wm volume changes 5years transplant twentyfour rrms participants underwent beambased hdit hct using twopiecewise mixedeffects model estimated shortterm baseline 1year longterm beyond 1year rates bvl hdit hct also compared rates based presence gadoliniumenhancing lesions baseline maintenance eventfree survival followupresultson average accelerated shortterm bvl 137 se 021 086 se 028 218 se 026 occurred wb gm wm respectively baseline t1weighted mri wm lesion volume significant predictor wb shortterm wm shortterm longterm average rates bvl initial acceleration 022 y se 010 013 y se 011 036 y se 011 wb gm wm respectively participants gadoliniumenhancing lesions baseline significantly higher shortterm rates gm 156 vs 027 p001 wb volume loss 194 vs 081 p0006 1year followup compared without gadoliniumenhancing lesions wm volume loss significantly different 259 vs 166 p016 participants maintained eventfree survival similar rates bvl compared notconclusionsbvl may accelerate months hdit hct however longterm adequate hdit hct may reduce bvl rates similar normal aging wb level,0.0
importance assessing life stress exposure multiple sclerosis case report abstractthis case report describes associations childhood adversity adult stress exposure multiple sclerosis ms highlight intersection mental health neurological illness persons ms pwms focus highadversity highresource patient selfreferred mental health services depression suicidal ideation without ever screened past current stress exposure ms common comorbid symptoms eg fatigue depression suicidality may affected adversity compounded pandemicrelated stressors including sociopolitical economic sequelae case illustrates potential benefit screening lifetime stressors mechanism improve case conceptualizations enable referrals mental health specialists promote coping resiliency reduce future ms morbidity illuminate stress important research focus deserves exploration pwms,0.0
multiple sclerosis diseasemodifying therapies covid19 systematic review immune response vaccination recommendations vaccines basel 2021 jul 11 9 7 773 doi 103390 vaccines9070773abstractunderstanding risks covid19 patients multiple sclerosis ms receiving diseasemodifying therapies dmts immune reactions vital analyze vaccine response dynamics systematic review covid19 course outcomes patients receiving different dmts conducted according preferred reporting items systematic reviews metaanalyses statement emerging data sarscov2 vaccines used elaborate recommendations data 4417 patients suggest ms per se portend higher risk severe covid19 general population advanced age comorbidities higher disability significantly impact covid19 outcomes dmts negligible influence covid19 incidence outcome causing severe lymphopenia hypogammaglobulinemia anticd20 therapies might tendency increased hospitalization worse outcomes higher risk reinfection blunted immune responses reported many dmts vaccination implications clinical evidence support increased risk ms relapse vaccination failure vaccination timing needs individually tailored cladribine alemtuzumab recommended wait 36 months last cycle vaccination general anticd20 therapies vaccination must deferred toward end cycle next dose administered least 46 weeks completing vaccination serological status vaccination highly encouraged growing clinical evidence continuous surveillance extremely important continue guiding future treatment strategies vaccination protocolspmid34358189 doi103390 vaccines9070773,0.0
prioritizing healthcare access concerns canadians ms mult scler j exp transl clin 2021 jul 11 7 3 20552173211029672 doi 101177 20552173211029672 ecollection 2021 julsepabstractbackground canadians ms high users healthcare services yet report multiple unmet needs high disease burden low satisfaction care engaging patients healthcare planning can lead improvements access care currently limited evidence harnessed perspectives canadians msobjective identify prioritize healthcare access concerns canadians msmethods crosssectional online survey informed concerns report methodology used address objective participants recruited multiple methods descriptive statistics used identify main barriers healthcare providers concerns report methods used calculate needs indexes prioritize concerns participantsresults 324 canadians ms participated study november 18 2019 march 27 2020 pressing healthcare access concerns canadians ms related availability healthcare providers ms knowledge affordability services aim improve wellnessconclusion findings provide healthcare planners prioritized access concerns canadians ms can used guide strategic planning improve quality life individualspmid34290879 pmcpmc8276490 doi101177 20552173211029672,0.0
sex disparities prevalence physical function disabilities populationbased study lowincome community background functional disability continues significant public health problem increases older adults vulnerability experience diminished quality life loss independence higher healthcare costs health services utilization increased risks mortality thus aimed study prevalence functional disabilities sex according types daily living activities controlling specific sociodemographic variables among older hispanics lowincome communitiesmethodswe used crosssectional epidemiological research design considering complex sampling design households interview adults 65 years living lowincome communities puerto rico functional disability measured promis physical function short form20 tscore selected community reported 5980 adult residents 65 years according usa census prevalence functional disability estimated using logistic regression model weighting effect sampling estimated prevalence compared sexes using prevalence ratio pr estimated logistic regression models controlling age income number chronic conditions high low impact chronic conditions functional disabilities marital status sampling designresultswe recruited 211 older hispanics randomly selected sample mean age 744 71 years female predominance 573 overall estimated prevalence physical function disability using tscore among females 270 95 ci 14 51 times estimated prevalence physical function disability among males women likely report functional disabilities instrumental activities daily living selfcare activities functional mobility compared males however sex differences largely explained presence musculoskeletal conditions high impact functional disabilityconclusionsthe females study bear greater burden physical function disability adult age health policies well future studies targeted reducing burden physical function disabilities different types daily activities gendersensitive disability selfmanagement programs,0.0
cognitive fatigability multiple sclerosis performance decline time paced auditory serial addition test abstractbackgroundcognitive fatigability cf can defined inability maintain optimal level performance throughout sustained cognitive task remains unclear however whether specific moment cognitive task paced auditory serial addition test pasat performance begins break thus present study aimed evaluate performance declines time pasat people multiple sclerosis pwms compared healthy controlsmethods178 pwms 186 control participants administered 3 2 pasat part larger battery neuropsychological tests examine cf differed groups repeated measures anovas used evaluate cumulative error rates made group throughout task addition error rate developed across task trial examined evaluate detail difference groups respect performance declined beginning end task lastly exploratory twoway independent sample anovas examined whether influence stimulus complexity single vs doubledigit answers task performanceresultscompared healthy controls pwms produced greater number errors overall pasat demonstrated vulnerability cf healthy controls reflected greater number errors made towards end task difference noticeable 3 pasat given difficulty groups experienced 2 form 3 pasat trial 37 pwms made significantly cumulative errors controls however rate error generation largely consistent linear beginning end group differences observed may partially attributable stimulus complexity influencing task performanceconclusionsthe 3 pasat sensitive group differences cf error generation 2 pasat respect cf greater vulnerability observed ms group due breakdown performance increase rate error generation specific point task rather linear decline performance start results suggest pwms struggle maintain optimal performance sustained cognitive effort beginning demonstrate steeper steady rate decline time,0.0
idiopathic intracranial hypertension multiple sclerosis overlap cureus 2021 jul 10 13 7 e16305 doi 107759 cureus16305 ecollection 2021 julabstractidiopathic intracranial hypertension iih multiple sclerosis ms occur higher incidence women childbearing age may associated clinical entities disease processes alter cerebrospinal fluid csf dynamics may present similarly headache visual changes report case 33yearold morbidly obese woman developed progressive worsening blurry vision unilateral temporal headache found papilledema prompted workup intracranial hypertension imaging csf findings suggestive demyelinating process ms addition iihpmid34381659 pmcpmc8352602 doi107759 cureus16305,1.0
retinal oct texture analysis differentiating healthy controls multiple sclerosis ms without optic neuritis biomed res int 2021 jul 10 20215579018 doi 101155 2021 5579018 ecollection 2021abstractmultiple sclerosis ms inflammatory disease damaging myelin sheath central peripheral nervous system brain spinal cord optic neuritis one prevalent ocular demonstrations ms current diagnosis protocol ms mri newer modalities like optical coherence tomography oct already interest early detection progression analysis oct reveals symptoms ms central nervous system cns crosssectional images neural retinal layers previous works oct mostly focused thickness retinal layers however texture features seem also information regard research introduce new pipeline constructs layerstacked ls images containing data specific layer variety texture features extracted ls images differentiate healthy controls noneon ms cases furthermore definition texture extraction methods tailored application performing vast survey available texture analysis methods treasury powerful features collected paper primary work paper shows ability features diagnosis hc ms noneon cases findings show texture features powerful diagnose ms cases furthermore adding information conventional thickness values texture features improves considerably discrimination target groups including hc vs ms hc vs msnoneon hc vs msonpmid34337030 pmcpmc8298144 doi101155 2021 5579018,1.0
efficacy safety temelimab multiple sclerosis results randomized phase 2b extension study abstractbackgroundthe envelope protein human endogenous retrovirus w hervwenv expressed macrophages microglia mediating axonal damage chronic active ms lesionsobjective methodsthis phase 2 doubleblind 48week trial relapsingremitting ms 48week extension phase assessed efficacy safety temelimab monoclonal antibody neutralizing hervwenv primary endpoint reduction cumulative gadoliniumenhancing t1lesions brain magnetic resonance imaging mri scans week 24 additional endpoints included numbers t2 t1hypointense lesions magnetization transfer ratio brain atrophy total 270 participants randomized receive monthly intravenous temelimab 6 12 18mg kg placebo 24weeks week 24 placebotreated participants rerandomized treatment groupsresultsthe primary endpoint met week 48 participants treated 18mg kg temelimab fewer new t1hypointense lesions p0014 showed consistent however statistically nonsignificant reductions brain atrophy magnetization transfer ratio decrease compared placebo comparator group latter two trends sustained 96weeks safety issues emergedconclusiontemelimab failed show effect features acute inflammation demonstrated preliminary radiological signs possible antineurodegenerative effects current data support development temelimab progressive mstrial registrationchangems clinicaltrialsgov nct02782858 eudract 201500405929 angelms clinicaltrialsgov nct03239860 eudract 201600493518,1.0
leukemia stem cellbone marrow microenvironment interplay acute myeloid leukemia development abstractdespite advances intensive chemotherapy regimens targeted therapies overall survival os acute myeloid leukemia aml remains unfavorable due inevitable chemotherapy resistance high relapse rate mainly caused persistence existence leukemia stem cells lscs bone marrow microenvironment bmm home hematopoiesis considered play crucial role hematopoiesis leukemogenesis interrupted aml cells malignant bmm formed thus provided refuge lscs protecting cytotoxic effects chemotherapy review summarized alterations bidirectional interplay hematopoietic cells bmm normal aml hematopoietic environment pointed key role alterations pathogenesis chemotherapy resistance aml finally focused current potential bmmtargeted strategies together future prospects challenges accordingly research necessary elucidate underlying mechanisms behind lscbmm interaction targeting interaction perceived potential therapeutic strategy eradicate lscs ultimately improve outcome aml,0.0
initial action output feedbackguided motor behaviors autism spectrum disorder background sensorimotor issues common autism spectrum disorder asd related core symptoms predictive worse functional outcomes deficits rapid behaviors supported primarily feedforward mechanisms continuous feedbackguided motor behaviors reported degrees distinct cosegregate within individuals across development well understoodmethodswe characterized behaviors varied involvement feedforward control relative feedback control across skeletomotor precision grip force oculomotor saccades control systems 109 individuals asd 101 agematched typically developing controls range 529 years including 58 individuals asd 57 controls completed grip saccade tests grip force examined across multiple force 15 45 85 mvc visual gain levels low medium high maximum grip force also examined grip force tests reaction time initial force output accuracy variability entropy examined saccade test latency accuracy trialwise variability latency accuracy examinedresultsrelative controls individuals asd showed similar accuracy initial grip force reduced accuracy saccadic eye movements specific older ages sample force variability greater asd relative controls saccade gain variability across trials different groups force entropy reduced asd especially older ages also find reduced grip strength asd severe dominant compared nondominant handslimitationsour agerelated findings rely crosssectional data longitudinal studies sensorimotor behaviors associations asd symptoms neededconclusionswe identify reduced accuracy initial motor output asd specific oculomotor system implicating deficient feedforward control may mitigated slower occurring behaviors executed periphery individuals asd showed increased continuous force variability similar levels trialtotrial saccade accuracy variability suggesting feedbackguided refinement motor commands deficient specifically adjustments occur rapidly continuous behavior also document reduced lateralization grip strength asd implicating atypical hemispheric specialization,0.0
new strategy ms treatment autoantigenmodified liposomes therapeutic effect j control release 2021 may 22s01683659 21 002510 doi 101016 jjconrel202105027 online ahead printabstractas current treatments multiple sclerosis ms remain chemotherapeutic ones directed toward symptoms development curative treatment urgently required herein show autoreactive immune celltargetable approach using autoantigenmodified liposomes curative treatment ms experiments experimental autoimmune encephalomyelitis eae induced autoantigenic myelin oligodendrocyte glycoprotein mog peptide used model primary progressive ms mogmodified liposomes encapsulating doxorubicin moglipdox used therapeutic drug results showed progression encephalomyelitis symptoms significantly suppressed moglipdox injection whereas samples failed show effect additionally invasion inflammatory immune cells spinal cord demyelination neurons clearly suppressed moglipdoxtreated mice facs analysis revealed number mogrecognizable cd4+ t cells spleen obviously decreased moglipdox treatment furthermore number effector th17 cells spleen significantly decreased regulatory treg cells concomitantly increased finally demonstrated myelin proteolipid protein plp modified liposomes encapsulating dox plplipdox also showed therapeutic effect relapsingremitting eae findings indicate autoantigenmodified liposomal drug produced highly therapeutic effect eae delivering encapsulated drug autoantigenrecognizable cd4+ t cells thus suppressing autoreactive immune responses present study suggests use autoantigenmodified liposomes promises suitable therapeutic approach cure mspmid34033858 doi101016 jjconrel202105027,1.0
exploring use cannabis substitute prescription drugs convenience sample background use cannabis medicine cam prescribed nonprescribed increased markedly last decade mirrored global shift cannabis policy towards permissive stance evidence cannabis functions substitute prescription drugs particularly opioids however knowledge needed motives substitution users patterns use perceived effects substitution useaimsto explore substitutes prescription drugs cannabis type prescription drugs substituted type cannabis used impact substitution cannabis prescription drug use well motives substitution terms experienced effects side effectsmethodsa selfselected convenience sample recruited social media public media patient organizations take part anonymous online survey inclusion criteria 18 years older use cannabis prescribed nonprescribed medical purposeresultsthe final sample included 2841 respondents majority 91 used nonprescribed cannabis half 546 used cam purpose replacing prescribed drug compared nonsubstitution users substitution users likely women use cam treatment chronic pain somatic conditions pain medication 672 antidepressants 245 arthritis medication 207 common types drugs replaced cam among substitution users 381 reported termination prescription drug use 459 substantial decrease prescription drug use frequent type cannabis used substitute cbdoil 652 followed hash pot skunk 366 half 658 found cam much effective compared prescription drugs 855 side effects associated prescription drug use much worse compared use camconclusioncam frequently used substitute prescription drugs particularly opioids research needed longterm consequences use cam including impact low high thc cannabis products specific somatic mental health conditions,0.0
efficacy safety fremanezumab patients episodic chronic migraine documented inadequate response 2 4 classes migraine preventive medications 6months treatment phase 3b focus study background fremanezumab fully humanized monoclonal antibody igg2a selectively targets calcitonin generelated peptide proven efficacy preventive treatment migraine study evaluated longterm efficacy safety tolerability monthly quarterly fremanezumabmethodsepisodic migraine chronic migraine patients completing 12week doubleblind period focus trial entered 12week openlabel extension received 3 monthly doses fremanezumab 225 mg changes baseline monthly migraine days monthly headache days least moderate severity days acute headache medication use days photophobia phonophobia days nausea vomiting disability scores proportion patients achieving 50 75 reduction monthly migraine days evaluatedresultsof 807 patients completed 12week doubleblind treatment period entered openlabel extension 772 patients completed study placebo quarterly fremanezumab monthly fremanezumab dosing regimens respectively patients fewer average monthly migraine days mean standard deviation change baseline 47 54 51 47 55 50 monthly headache days least moderate severity 45 50 48 45 52 49 days per month acute headache medication use 43 52 49 46 48 49 days photophobia phonophobia 31 53 34 53 40 52 days nausea vomiting 23 46 31 45 30 44 12week openlabel extension 38 45 46 patients respectively achieved 50 reduction 16 15 20 respectively achieved 75 reduction monthly migraine days disability scores substantially improved 3 treatment groups low rates adverse events leading discontinuation 1 conclusionfremanezumab demonstrated sustained efficacy 6 months well tolerated patients episodic migraine chronic migraine documented inadequate response multiple migraine preventive medication classestrial registrationclinicaltrialsgov nct03308968 focus,0.0
genetic susceptibility multiple sclerosis interactions conserved extended haplotypes mhc susceptibility regions background study accumulation msrisk resulting different combinations msassociated conservedextendedhaplotypes cehs mhc three nonmhc riskhaplotypes nearby genes eomes zfp36l1 clec16a many haplotypes msassociated despite populationfrequencies exceeding percentage geneticallysusceptible individuals basis frequencydisparity requires explanationmethodsthe snpdata wtccc phased mhc three nonmhc susceptibilityregions cehs mhc classified five haplotypegroups hladrb11501 dqb10602 a1 containing h + extendedrisk er allprotective ap neutral 0 singleceh c1 msassociations different riskcombinations mhc nonmhc riskloci appropriateness additive multiplicative riskaccumulation models assessedresultsdifferent combinations riskhaplotypes produce final msrisk closer additive rather multiplicative riskmodels neither model consistent thus h + haplotypes greater impact combined 0 haplotypes h + haplotypes whereas h + haplotypes greater impact combined c1 haplotypes 0 haplotypes similarly riskgenotypes 0 h + c1 h + h + h + 0 c1 additive risks nonmhc riskloci whereas riskgenotypes er h + ap c1 unaffectedconclusionsgeneticsusceptibility ms essential ms develop actually developing ms depends heavily upon individuals particular combination riskhaplotypes loci interact,0.0
personalized bcell tailored dosing ocrelizumab patients multiple sclerosis covid19 pandemic abstractin observational study 159 patients multiple sclerosis received personalized dosing ocrelizumab incentivized covid19 pandemic redosing scheduled cd19 bcell count 10cells l starting 24weeks previous dose repeated 4weekly median interval redosing last bcell count 34 3038 weeks clinical relapses reported minority patients showed expanded disability status scale edss progression monthly serum neurofilament light levels remained stable extended intervals two 19 107 patients followup magnetic resonance imaging mri scan showed radiological disease activity personalized dosing ocrelizumab significantly extend intervals low shortterm disease activity incidence encouraging future research longterm safety efficacy,0.0
isoflavone diet ameliorates experimental autoimmune encephalomyelitis modulation gut bacteria depleted patients multiple sclerosis sci adv 2021 jul 9 7 28 eabd4595 doi 101126 sciadvabd4595 print 2021 julabstractthe gut microbiota potential environmental factor influences development multiple sclerosis ms others demonstrated patients ms healthy individuals distinct gut microbiomes however pathogenic relevance differences remains unclear previously showed bacteria metabolize isoflavones less abundant patients ms suggesting isoflavonemetabolizing bacteria might provide protection ms using mouse model ms report isoflavone diet provides protection disease dependent presence isoflavonemetabolizing bacteria metabolite equol notably composition gut microbiome mice fed isoflavone diet exhibited parallels healthy human donors whereas composition fed isoflavonefree diet exhibited parallels patients ms collectively study provides evidence dietaryinduced gut microbial changes alleviate disease severity may contribute ms pathogenesispmid34244137 doi101126 sciadvabd4595,0.0
highthroughput screening circrnas reveals novel mechanisms tuberous sclerosis complexrelated renal angiomyolipoma abstractobjectivetuberous sclerosis complex tsc rare autosomal dominant disease characterized lesions throughout body previous study showed abnormal upregulation mirnas plays important part pathogenesis tscrelated renal angiomyolipoma tscraml circrnas known important regulators mirna little known circrnas tscramlsmethodsmicroarray chips rna sequencing used identify circrnas mrnas differently expressed tscraml normal kidney tissue competitive endogenous rna cerna regulatory network constructed reveal regulation mirnas mrnas circrnas biological functions circrna mrna analyzed pathway analysis microenvironmental cell types estimated mcpcounter packageresultswe identified 491 differentially expressed circrnas decs 212 differentially expressed genes degs 6 decs confirmed qpcr cerna regulatory network included 6 decs 5 mirnas 63 mrnas established lipid biosynthetic process significantly upregulated tscraml humoral immune response leukocyte chemotaxis pathway found downregulated fibroblasts enriched tscraml upregulation circrna_000799 circrna_025332 may significantly correlated infiltration fibroblastsconclusioncircrnas may regulate lipid metabolism tscraml regulation mirnas fibroblasts enriched tscramls population fibroblast may related alteration circrnas tscraml lipid metabolism fibroblasts potential treatment target tscraml,0.0
distributional characteristics multiple sclerosis lesions quantitative susceptibility mapping correlation clinical severity front neurol 2021 jul 9 12647519 doi 103389 fneur2021647519 ecollection 2021abstractbackground multiple sclerosis ms patients wide spectrum severity responses therapy personalization treatment relies sensitive specific biomarkers previous studies suggested susceptibility contrast demyelinated plaques associated ironrelated pathology multiple sclerosis may indicate clinical severity aims study characterize spatial distribution ms lesions different iron patterns using quantitative susceptibility mapping explore neuroradiological findings correlate poor clinical outcome methods twentysix patients relapsingremitting ms 14 men 12 women mean age 29 8 standard deviation years age range 2152 years included study differences lesion number t2 volume susceptibility compared among lesions subcategorized location presence absence hyperintense rim quantitative susceptibility mapping associations imaging features clinical outcomes including expanded disability status scale scores annual relapse rates investigated results total 811 unifocal ms lesions included qsm patterns nodular hyperintensity rim rim 540 67 hyperintense rim edge rim+ 172 21 nodular isointensity 99 12 rim+ lesions significantly larger volume 115 142 vs 166 185 mm3 p 0001 lower susceptibility 4 15 vs 8 16 ppb p 005 rim lesions rim+ lesions found periventricular areas median 45 interquartile range iqr 36 whereas larger proportion rim lesions distributed juxtacortical median 32 iqr 21 deep white matter median 38 iqr 22 areas annual relapse rate positively correlated proportion periventricular rim+ lesions p 0001 r 065 proportion subtentorial rim+ lesions p 005 r 040 additionally significant association found burden periventricular rim+ lesions 064 p 0001 burden subtentorial rim lesions 036 p 005 conclusions high number lesion burden periventricular rim+ lesions subtentorial lesions associated frequent clinical relapsespmid34305779 pmcpmc8299522 doi103389 fneur2021647519,1.0
rituximab induced cytokine release syndrome ms patient case report clin case rep 2021 jul 9 9 7 e04407 doi 101002 ccr34407 ecollection 2021 julabstractcytokine release syndrome rituximab reported certain diseases however rarely reported ms patients treated rituximab treating physician suspect syndrome typical signs symptoms appearpmid34267900 pmcpmc8271264 doi101002 ccr34407,0.0
work productivity trajectories australians living multiple sclerosis groupbased modelling approach abstractbackgroundstudies documented reduced work capacity work productivity loss multiple sclerosis ms little known longitudinal trajectories work productivity msobjectivesto examine trajectories work productivity people living multiple sclerosis pwms factors associated trajectoriesmethodsstudy participants employed participants australian ms longitudinal study amsls followed 2015 2019 least two repeated measures n2121 used groupbased trajectory modelling identify unique work productivity trajectories pwmsresultswe identified three distinct trajectories work productivity moderately reducednull 170 participants mean work productivity level 476 2015 slope 097 per year p 022 mildly reducednull 467 mean work productivity 863 2015 slope 070 per year p012 fullnull 363 mean work productivity 997 2015 slope 029 per year p 030 higher education level higher disability higher ms symptom severity associated increased probability worse work productivity trajectoryconclusionwe identified three distinct work productivity trajectories pwms stable time differentiated baseline level work productivity,0.0
quantitative magnetic resonance imaging analysis early markers upper cervical cord atrophy multiple sclerosis neuromyelitis optica spectrum disorder mult scler int 2021 jul 9 20219917582 doi 101155 2021 9917582 ecollection 2021abstractpurpose quantitatively analyze c2 c3 segments spinal cord magnetic resonance imaging mri scans neuromyelitis optica spectrum disorder nmosd relapsingremitting multiple sclerosis rrms patients first five years disease investigate intergroup differences regarding markers spinal cord atrophy correlations expanded disability status scale edss materials methods twenty nmosd patients twenty rrms patients within first five years disease enrolled crosssectional study patients underwent spinal cord mr imaging using 15 tesla systems c2 c3 portions spinal cord segmented obtained scans c2 c3 anteroposterior diameter c2 c3 scapd transversal diameter c2 c3 sctd crosssectional area c2 c3 sccsa quantitatively measured using spinal cord toolbox v43results three nmosd patients seropositive antiaqp4 igg mean c2 c3 sccsa nmosd patients significantly lower rrms patients nmosd patients significantly lower c2 c3 sctds rrms patients three antiaqp4+ patients excluded analysis c2 c3 sctd negatively correlated edssconclusion early stages disease quantitative evaluation c2 c3 spinal cord parameters including crosssectional area transversal diameter nmosd patients appears potential diagnostic prognostic valuepmid34306756 pmcpmc8285164 doi101155 2021 9917582,0.0
mri contributes accurate early diagnosis nonradiographic hlab27 negative axial spondyloarthritis background nonradiographic axial spondyloarthropathies nraxspa diagnosed absence radiographic sacroiliitis presence bone marrow edema bme magnetic resonance imaging mri according classification criteria international assessment spondyloarthritis society asas structural changes sacroiliac joints sijs mri used criteria absence bme however less half asian patients clinically active axspa show bme incidence human leukocyte antigen hla b27 low asian populations makes difficult identify nraxspa used mri evaluate structural damage sijs patients nraxspa without bme aim identifying best methodology accurate diagnosis especially populations less common bme hlab27methodsone hundred three patients inflammatory back pain included prospective study patients radiograph met definition positive modified new york criteria bme structural damage sij including sclerosis erosion assessed independently coronal axial shorttau inversion recovery t1weighted spin echo mri scans two welltrained musculoskeletal radiologists using spondyloarthritis research consortium canada sparcc score demographics patients collected disease characteristics structural damage analyzed patients without bme sij mri receiver operating characteristic roc curve analysis used assess diagnostic performance structural damageresultsall individuals cohort least one abnormal finding sij mri including bme structural damage 36 103 patients bme identified significant positive correlation sparcc scores severe erosion assessed focal joint space widening fjsw p 0001 36 patients fiftyeight 103 enrolled patients fulfilled asas criteria nraxspa either absence presence bme 58 patients 57 19 erosions fjsw respectively presence bme significantly correlated fjsw phi score 0319 p 0015 demonstrated significant positive correlation fjsw either presence severity bme patients nraxspa met asas definition positive correlation bme fjsw across whole study cohort phi score 0389 p 0001 area roc curve auc fjsw sij mri 0736 p 0001 hlab27positive negative groups bme common presence fjsw phi scores 0370 0377 p 0018 0003 respectively sparcc scores higher patients fjsw p 0001 p 0005 also identified positive correlation fjsw bme patients nraxspa normal serum levels creactive protein phi score 0362 p 0001 conclusionstructural damage detected sij mri sclerosis erosions fjsw may present patients without detectable inflammation sij mri however fjsw significantly correlated severity inflammation seen sij mri contributes accurate diagnosis nraxspa used alternative diagnostic test nraxspa general population especially carry hlab27 gene asian patients without bme patients normal serum inflammatory biomarkers,0.0
still rely edss evaluate disability multiple sclerosis patients study inter intra rater reliability abstractbackgroundfew studies assessed reliability interrater variability edss functional parameters fp ratingobjectiveto evaluate interrater variability errors edss fp rating junior jn ms neurologists msn methodpatients ms examined jn msn day assessor rated fp edss used smartphone app get automated calculation fp smartphone fp sfp edss smartphone edss sedss description neurological exam interrater variability assessed comparing jn msn ratings method intrarater variability assessed comparing traditional digital rating given assessorresult103 patients included perfect agreement jn msn met 67 70 patients regarding edss sedss disagreement lead significant difference terms level disability occurred 17 edss 12 sedss p007 regarding intrarater reliability found 38 rating discrepancies jn 14 msn p004 conclusionwe found significant interrater variability well substantial frequency rating errors jn use less subjective easiertorate scales encouraged,0.0
association serum levels antibodies aldoa fh4 transient ischemic attack cerebral infarction background ischemic stroke including transient ischemic attack tia acutephase cerebral infarction aci serious health problem aging society thus study aimed identify tia aci biomarkersmethodsin 19 patients tia candidate antigens recognized serum igg autoantibodies screened using human aortic endothelial cell cdna library amplified luminescent proximity homogeneous assaylinked immunosorbent assay alphalisa serum antibody levels candidate antigens examined healthy donor hd tia aci cohorts n 285 92 529 plasma antibody levels japan public health centerbased prospective cohort study 19911993 also examinedresultsthe candidate antigens aldolase aldoa fumarate hydratase fh alphalisa patients tia aci higher antialdoa antibody aldoaab antifh antibody fhab levels hds p 005 multivariate logistic regression analysis aldoaab odds ratio 246 p 00050 fhab 249 p 00037 levels independent predictors tia according casecontrol study aldoaab 250 p 001 fhab 260 p 001 levels associated aci risk correlation analysis aldoaabs fhabs well associated hypertension coronary heart disease habitual smoking antibody levels also correlated well maximum intimamedia thickness reflects atherosclerotic stenosisconclusionsaldoaabs fhabs can novel potential biomarkers predicting atherosclerotic tia aci,0.0
proteomics multiple sclerosis inherent issues defining pathoetiology identifying early biomarkers int j mol sci 2021 jul 9 22 14 7377 doi 103390 ijms22147377abstractmultiple sclerosis ms demyelinating disease human central nervous system unconfirmed pathoetiology although animal models used mimic pathology clinical symptoms single model successfully replicates full complexity ms initial clinical identification disease progression importantly lack preclinical biomarkers hampering earliest possible diagnosis treatment notably development rationally targeted therapeutics enabling preemptive treatment halt disease also delayed without biomarkers using literature mining bioinformatic analyses review assessed available proteomic studies ms patients animal models discern 1 whether models effectively mimic ms 2 whether reasonable biomarker candidates identified implication necessity assessing proteoforms critical importance identifying rational biomarkers discussed moreover challenges using different proteomic analytical approaches biological samples also addressedpmid34298997 doi103390 ijms22147377,1.0
autoimmune pulmonary alveolar proteinosis successfully treated lung lavage adolescent patient case report background pulmonary alveolar proteinosis rare interstitial lung disease characterized accumulating surfactant materials alveoli autoimmune form far common adults pediatric age group vast majority cases congenital report case adolescent patient diagnosed autoimmune pulmonary alveolar proteinosis unusual age groupcase presentationa15 yearold saudi male presented emergency department history shortness breath low oxygen saturation highresolution computed tomography chest showed global crazypaving pattern autoantibodies granulocytemacrophage colonystimulating factor detected serum diagnosis autoimmune form pulmonary alveolar proteinosis confirmed excluding possible causes patient improved underwent whole lung lavage general anesthesia independent oxygen therapy 6 months followupconclusionthe autoimmune form pulmonary alveolar proteinosis rare pediatric age group considered apparent cause disease found whole lung lavage first treatment modality offered setting close followup monitoring,0.0
alopecia universalis occurring alemtuzumab treatment multiple sclerosis twoyear followup two patients int j environ res public health 2021 jul 9 18 14 7338 doi 103390 ijerph18147338abstractalopecia universalis au severe form alopecia areata caused cytotoxic tcells reacting follicular autoantigens producing complete loss scalp body hair alemtuzumab highly efficacious monoclonal antibody used treatment multiple sclerosis ms causes secondary autoimmunity 40 patients many factors believed contribute process pathogenic mechanisms well clear date three cases au treatment alemtuzumab reported paper report cases two patients developed au 12 months second cycle alemtuzumab review literature one year end second cycle two female patients thirties experienced complete hair loss first case temporally associated significant drop vitamin d vd levels second case accompanied joint swelling patients thyroid alterations showed hair regrowth 2year followup au must considered among secondary autoimmune manifestations alemtuzumab treatment emphasize need appropriate patient screening thorough clinical surveillance factors predisposing patients secondary autoimmunitypmid34299789 doi103390 ijerph18147338,0.0
immunomodulation il17 tnf spondyloarthritis focus eye central nervous system ther adv musculoskelet dis 2021 jul 9 131759720x211025894 doi 101177 1759720x211025894 ecollection 2021abstracttumor necrosis factor alpha tnf interleukin17 il17 two proinflammatory cytokines involved pathophysiology spondyloarthritis spa therapies targeting tnf il17 used second line among spa patients failing nonsteroidal antiinflammatory drugs choice treatment take account patients comorbidities neurologic diseases common association spa deserves studied therefore role tnf il17 cytokines worth investigating neuropsychiatric diseases review aimed explore role tnf il17 pathogenesis uveitis multiple sclerosis neuromyelitis optica alzheimers disease parkinsons disease depression update critical guide therapeutic management comorbidities spa patientspmid34290832 pmcpmc8273400 doi101177 1759720x211025894,0.0
stem cell therapies progressive multiple sclerosis front cell dev biol 2021 jul 9 9696434 doi 103389 fcell2021696434 ecollection 2021abstractmultiple sclerosis ms chronic inflammatory disease central nervous system characterized demyelination axonal degeneration ms patients typically present relapsingremitting rr disease course manifesting sporadic attacks neurological symptoms including ataxia fatigue sensory impairment several effective diseasemodifying therapies able address inflammatory relapses associated rrms patients will inevitably advance progressive disease course marked gradual irreversible accrual disabilities therapeutic intervention progressive ms pms suffers lack wellcharacterized biological targets hence dearth successful drugs medications approved treatment pms typically limited efficacy active forms disease little impact slowing degeneration fail promote repair looking address unmet needs multifactorial therapeutic benefits stem cell therapies particularly compelling ostensibly providing neurotrophic support immunomodulation cell replacement stem cell transplantation holds substantial promise combatting complex pathology chronic neuroinflammation herein explore current state preclinical clinical evidence supporting use stem cells treating pms discuss prospective hurdles impeding translation revolutionary regenerative medicinespmid34307372 pmcpmc8299560 doi103389 fcell2021696434,1.0
unprovoked serotonin syndromelike presentation sarscov2 infection small case series sage open med case rep 2021 jul 8 92050313x211032089 doi 101177 2050313x211032089 ecollection 2021abstractclinicians researchers reported array neurological abnormalities coronavirus disease 2019 covid19 serotonin excess observed unaware reports central nervous system serotonin toxicity covid19 present two cases resemble serotonin syndrome covid19 without identifiable inciting medications 54yearold multiple sclerosis diabetes mellitus presented altered mental status altered sensorium attributed diabetic ketoacidosis condition quickly deteriorated fever 105 degrees fahrenheit rigidity extremities inducible clonus hyperreflexia intubated treated possible meningitis seizure neurologic workup negative acute pathology despite acetaminophen core temperature remained elevated 105 degrees fahrenheit treated external cooling cyproheptadine within 48 h fever rigidity hyperreflexia clonus resolved extubated discharged home day 14 72yearold hyperlipidemia admitted tremors 4 days testing positive covid19 symptoms rapidly worsened transferred intensive care unit day 3 extremis febrile 1044 degrees fahrenheit heart rate 180 beats per minute apparent whole body myoclonus intubated developed fever refractory acetaminophen requiring external cooling extensive neurologic workup negative received cyproheptadine slowly improved extubated discharged rehab day 11 cases represent unique presentation covid19 must considered requires high index suspicionpmid34290872 pmcpmc8274092 doi101177 2050313x211032089,0.0
realworld effectiveness natalizumab korean patients multiple sclerosis front neurol 2021 jul 8 12714941 doi 103389 fneur2021714941 ecollection 2021abstractbackground purpose natalizumab highly efficacious diseasemodifying therapy relapsingremitting multiple sclerosis ms data efficacy safety profile natalizumab asian patients ms limited study assessed efficacy safety natalizumab korean patients ms realworld setting methods study enrolled consecutive korean patients active relapsingremitting ms treated natalizumab least 6 months 2015 2021 evaluate therapeutic outcome natalizumab used expanded disability status scale edss scores brain magnetic resonance imaging adverse events assessed regular intervals evidence disease activity neda defined clinical relapse worsening edss score radiological activities results fourteen subjects ms included study mean age initiation natalizumab therapy 32 years patients positive antijohn cunningham virus antibodies natalizumab administration mean annual relapse rate markedly reduced 27 32 natalizumab therapy 01 04 natalizumab therapy p 0001 disability either improved stabilized natalizumab treatment 13 patients 93 1st year 2 years initiating natalizumab neda3 achieved 11 12 92 9 11 82 patients respectively progressive multifocal leukoencephalopathy serious adverse events leading discontinuation natalizumab observed conclusions natalizumab therapy showed high efficacy treating korean patients active ms without unexpected safety problemspmid34305808 pmcpmc8299833 doi103389 fneur2021714941,0.0
dissecting histone deacetylase 3 multiple disease conditions selective inhibition promising therapeutic strategy j med chem 2021 jun 23 doi 101021 acsjmedchem0c01676 online ahead printabstractthe acetylation histone nonhistone proteins implicated several disease states modulation epigenetic modifications therefore made histone deacetylases hdacs important drug targets hdac3 among various class hdacs signified potentially validated target multiple diseases namely cancer neurodegenerative diseases diabetes obesity cardiovascular disorders autoimmune diseases inflammatory diseases parasitic infections hiv however handful hdac3selective inhibitors reported spite continuous efforts design development hdac3selective inhibitors perspective roles hdac3 various diseases well numerous potent hdac3selective inhibitors discussed detail will surely open new vista discovery newer effective selective hdac3 inhibitorspmid34161101 doi101021 acsjmedchem0c01676,0.0
effectiveness virtual reality rehabilitation persons multiple sclerosis systematic review metaanalysis randomized controlled trials abstractbackgroundmultiple sclerosis ms chronic disease physical cognitive psychosocial impairments virtual reality vr used innovative tool neurological rehabilitation promising new studies used commercial video games consoles rehabilitation people msobjectivesthe aim systematic review summarize effectiveness using vr functional mobility fatigue quality life balance people ms compared conventional exercises interventionmethodssix databases scielo lilacs pubmed cochrane library embase pedro searched using following terms virtual reality multiple sclerosis randomized controlled trial two reviewers performed search selection extraction data studies methodological quality articles assessed using pedro scale risk bias independently assessed two reviewers using cochrane collaboration risk bias tool mean differences confidence intervals combined calculated metaanalysisresultsnine randomized clinical trials included total sample 424 participants general functional mobility presented similar improvement groups fatigue quality life balance vr promoted improvement equal greater conventional exercises metaanalysis confirmed functional mobility vr promote significant improvement fatigue quality life balance vr promotes superior improvementconclusionthis systematic review demonstrated positive effect using vr people ms relation fatigue quality life balance compared conventional exercises functional mobility vr associated conventional exercises seem bring additional benefits larger methodologically robust studies needotherthere funding systematic review prospero registration number crd42021226471,0.0
coexistence alport syndrome c3 glomerulonephritis proband family history background alport syndrome c3 glomerulonephritis c3gn rare kidney diseases frequently responsible familial haematuria proteinuria renal impairment rapid development molecular genetic testing alport syndrome causes restricted mostly variants col4a5 col4a3 col4a4 genes moreover broad range genetic contributors complement complementregulating proteins definitely implicated pathogenesis c3gnmethodswe sought family persistent microscopic haematuria associated renal failure clinicopathologic followup data obtained molecular genetic testing used screen pathogenic variantsresultswe describe threegeneration family alport syndrome showing dominant maternal inheritance notably renal biopsy showed concurrent histological evidence c3gn proband harbouring uncommon heterozygous variation cfhr5 c508g alteration leads replacement highly conserved residue position 170 strand subunit cfhr5 pval170met silico analysis showed variation predicted deregulate complement activation altering structural properties enhancing c3b binding capacity compete complement factor h cfh line experimental data previously publishedconclusionsthe comorbidity findings alport syndrome c3gn indicate underlying overlap require study,0.0
significant differences absenteeism academic achievements norwegian multiple sclerosis case control study abstractbackgroundthe duration features multiple sclerosis ms prodrome well defined aimed ascertain whether people future ms diagnosis days absence perform worse upper secondary school age gender countymatched controlsmethodsusing registry data southeast norway identified people ms born 1978 statistics norway provided information grades days absence cases matched controls looked absence three years upper secondary school grades compulsory subjects norwegian english mathematics physical educationresultswe identified 107 cases disease onset one year graduation 626 controls significant differences absence grades achieved population whole disease onset within four years diagnosis association time disease onset days absence gradesconclusionthere difference days absence grades achieved upper secondary school four years leading disease onset cases compared controls potential prodrome may affect cognition enough impact school achievements,0.0
progressive tumefactive demyelination result extensive diagnostic workup case report front neurol 2021 jul 8 12701663 doi 103389 fneur2021701663 ecollection 2021abstracttumefactive demyelinating lesions belong rare variants multiple sclerosis posing diagnostic challenge since difficult distinguish neoplasm brain lesions require careful differential diagnosis contribution presents case report young female progressive tumefactive demyelinating brain spinal cord lesions extensive diagnostic process including two brain biopsies autopsy reveal explanatory diagnosis multiple sclerosis patient treated various diseasemodifying treatments without significant effect died ascendent infection via ventriculoperitoneal shunt resulting staphylococcus aureus meningitispmid34305803 pmcpmc8297737 doi103389 fneur2021701663,1.0
white blood cell counts highdensity lipoprotein cholesterol ratio novel predictor longterm adverse outcomes patients percutaneous coronary intervention retrospective cohort study front cardiovasc med 2021 jul 8 8616896 doi 103389 fcvm2021616896 ecollection 2021abstractbackground white blood cell wbc counts highdensity lipoprotein cholesterol hdlc widely available clinical practice however predictive value cardiovascular disease cvd uncertain present study firstly assessed prognostic value wbc hdlc ratio whr patients coronary artery disease cad underwent percutaneous coronary intervention pci methods six thousand fifty patients cad pci retrospective cohort study identifier chictrinr16010153 evaluated initially three hundred seventyone patients excluded due hdl cholesterol data available malignancy dementia psoriasis eczema systemic connective tissue disorders multiple sclerosis chronic liver disease chronic obstructive pulmonary disorder finally 5 679 patients included study primary outcome longterm mortality secondary endpoints mainly major adverse cardiovascular cerebrovascular events macces defined combination stroke cardiac death stent thrombosis recurrent myocardial infarction target vessel revascularization mean followup time study 359 225 months defined best cutoff value mhr according receiver operating curve roc patients divided high low whr groups according cutoff value analyzed data acute coronary syndrome group acs stable cad subgroup respectively results overall 293 cases longterm mortality followup period according cutoff value whr 825 1 901 acs patients divided high whr group n 724 low whr group n 1 177 compared low whr group incidence allcause mortality acm 55 vs 36 p 0048 cardiac death 47vs 29 p 0042 significantly higher high whr group stable cad group also found incidence acm cardiac death significantly higher high group compared low group find significant difference high low whr group incidence macces multivariate cox proportional hazards model showed increased whr level independently correlated mortality high whr group risk acm increased two times acs adjusted hr 2036 12583296 p 0004 15 times stable cad adjusted hr 1586 11782136 p 0002 conclusion present study indicated increased wbc count hdlc ratio independently associated longterm mortality cad patients underwent pcipmid34307487 pmcpmc8295559 doi103389 fcvm2021616896,0.0
patient neurologist preferences united states relapsingremitting multiple sclerosis treatments findings discrete choice experiment patient prefer adherence 2021 jul 8 1515151527 doi 102147 ppas306498 ecollection 2021abstractbackground objective relapsingremitting multiple sclerosis rrms chronic inflammatory disease associated central nervous system dysfunction accelerated brain volume loss bvl exists paucity research examining importance bvl patients neurologists exploring whether preferences may differ two groups study sought evaluate preferences patients neurologists rrms treatments considering benefits risks associated novel common diseasemodifying therapies dmts patients methods us patients diagnosed nonhighly active rrms usbased neurologists completed online crosssectional survey discrete choice experiment used assess patient neurologist treatment preferences neurologists considering preferences patients nonhighly active rrms respondents chose two treatment profiles seven attributes identified qualitative research 2year disability progression 1year relapse rate rate bvl risks gastrointestinal symptoms flulike symptoms infection lifethreatening events attributelevel weighted preferences estimated using hierarchical bayesian modelresults analyses included 150 patients nonhighly active rrms mean age 54 years 150 neurologists 65 private practice among patients important treatment attribute reducing rate bvl followed reducing risk infection risk flulike symptoms contrast important treatment attribute among neurologists reducing risk lifethreatening event followed slowing rate 2year disability progression risk infectionconclusion findings highlight differences treatment preferences us patients neurologists nonhighly active rrms importance placed patients slowing rate bvl makes key topic covered shared decisionmaking processpmid34267507 pmcpmc8275192 doi102147 ppas306498,0.0
autismassociated biomarkers testretest reliability relationship quantitative social trait variation rhesus monkeys background rhesus monkeys macaca mulatta exhibit pronounced individual differences social traits measured macaque social responsiveness scalerevised macaque social responsiveness scale previously adapted social responsiveness scale instrument designed assess social autistic trait variation humans better understand potential biological underpinnings behavioral variation evaluated traitlike consistency several biological measures previously implicated autism eg arginine vasopressin oxytocin receptors well erk1 2 pten akt 13 rasmapk pi3kakt pathways also tested biological measures predicted macaque social responsiveness scalerevised scoresmethodscerebrospinal fluid blood samples collected n 76 male monkeys sample showed continuous distribution macaque social responsiveness scalerevised subset subjects n 43 samples collected thrice 10month period following statistical tests used case 2a intraclass correlation coefficients consistency principal component analysis general linear modelingresultsall biological measures except akt showed significant testretest reliability within individuals across time points next performed principal component analysis data monkeys complete biological measurement sets first time point n 57 explore potential correlations reliable biological measures relationship macaque social responsiveness scalerevised score threecomponent solution found followup analyses revealed cerebrospinal fluid arginine vasopressin concentration biological measure robustly predicted individual differences macaque social responsiveness scalerevised scores monkeys lowest cerebrospinal fluid arginine vasopressin concentration exhibited greatest social impairment finally confirmed result held larger study sample cerebrospinal fluid arginine vasopressin values available n 75 subjects conclusionsthese findings indicate cerebrospinal fluid arginine vasopressin concentration stable traitlike measure linked quantitative social trait variation male rhesus monkeys,0.0
plgabased nanoparticles neuroprotective drug delivery neurodegenerative diseases pharmaceutics 2021 jul 8 13 7 1042 doi 103390 pharmaceutics13071042abstracttreatment neurodegenerative diseases become one challenging topics last decades due prevalence increasing societal cost crucial point noninvasive therapeutic strategy neurological disorder treatment relies drugs passage bloodbrain barrier bbb indeed biological barrier involved cerebral vascular homeostasis tight junctions example one way overcome limit deliver neuroprotective substances brain relies nanotechnologybased approaches poly lacticcoglycolic acid nanoparticles plga nps biocompatible nontoxic provide many benefits including improved drug solubility protection enzymatic digestion increased targeting efficiency enhanced cellular internalization review will present overview latest findings advances plga npbased approach neuroprotective drug delivery case neurodegenerative disease treatment ie alzheimers parkinsons huntingtons diseases amyotrophic lateral multiple sclerosis pmid34371733 doi103390 pharmaceutics13071042,1.0
lesion probability mapping ms patients using regression network mr fingerprinting background develop regression neural network reconstruction lesion probability maps magnetic resonance fingerprinting using echoplanar imaging mrfepi addition t_1 t_2 nawm gm probability mapsmethodswe performed mrfepi measurements 42 patients multiple sclerosis 6 healthy volunteers along two sites unet trained reconstruct denoised distortion corrected t_1 t_2 maps additionally generate nawm gm wm lesion probability mapsresultswm lesions predicted dice coefficient 061pm 009 lesion detection rate 085pm 025 threshold 33 network jointly enabled accurate t_1 t_2 times relative deviations 52 51 average dice coefficients 092pm 004 091pm 003 nawm gm binarizing threshold 80conclusiondl promising tool prediction lesion probability maps fraction time might clinical interest wm lesion analysis ms patients,0.0
associations cd160 polymorphisms autoimmune thyroid disease casecontrol study background recent researches suggest cd160 hvem light btla signaling pathway may contribute pathogeneses autoimmune diseases relationship cd160 polymorphisms autoimmune thyroid disease aitd reported yet study aimed evaluate associations cd160 polymorphisms aitdmethodsa total 1017 patients aitd 634 graves disease 383 hashimotos thyroiditis 856 unrelated healthy controls recruited study odds ratios ors 95 confidence interval 95ci calculated logistic regression analyses cd160 snps detected using hisnp highthroughput genotypingresultsthere statistically significant difference graves disease patients control group respect genotype distribution p 0014 allele frequency rs744877 p 0034 significant association cd160 rs744877 aitd observed adjusted age gender dominant model 079 95ci 066095 p 0013 additive model 077 95ci 064094 p 0008 also observed adjusted age gender dominant model 078 95ci 065095 p 0011 additive model 076 95ci 063093 p 0007 significant association rs744877 graves disease observed allele model 084 95ci 071098 p 0027 dominant model 074 95ci 060091 p 0005 additive model 072 95ci 058090 p 0004 multivariate logistic regression analyses suggested association remained significant adjustment age gender however rs744877 related hashimotos thyroiditis furthermore cd160 rs3766526 significantly related either graves disease hashimotos thyroiditisconclusionthis first identification association cd160 rs744877 graves disease findings add new data genetic contribution graves disease susceptibility support crucial role cd160 hvem light btla pathway pathogenesis graves disease,0.0
implication human endogenous retrovirus w family envelope hepatocellular carcinoma promotes mek erkmediated metastatic invasiveness doxorubicin resistance cell death discov 2021 jul 8 7 1 177 doi 101038 s41420021005625abstracthuman endogenous retrovirus hervs originating exogenous retroviral infections germ cells millions years ago potential human diseases syncytin1 envelope protein encoded herv w family participates contexts schizophrenia multiple sclerosis diabetes several types cancers nevertheless report expression pattern potential mechanism syncytin1 hcc found syncytin1 expression upregulated hcc compared adjacent nontumorous tissues especially advanced hcc syncytin1 independent risk factor predict vascular invasion metastasis larger tumor size poor prognosis hcc patients analysis discovered syncytin1 overexpression positively associated hcc patients serum hbsag positive functional experiments vitro vivo demonstrated syncytin1 enhanced cell proliferation metastasis tumorigenicity hcc kyoto encyclopedia genes genomes kegg pathway analysis suggested mitogenactivated protein kinase mek extracellular signalregulated protein kinase erk pathway involved hcc clinical data indicated levels phosphorylation mek1 2 erk1 2 increased hcc comparing adjacent nontumorous tissues showed linear correlation syncytin1 expression upregulated mek1 2 erk1 2 phosphorylation levels hcc furthermore syncytin1 activated mek erk pathway hcc cells indepth research showed inflammationactivated mek erk pathway essential syncytin1 promoted hepatocarcinogenesis syncytin1 suppressed doxorubicininduced apoptosis via mek erk cascade conclusion syncytin1 promoted hcc progression doxorubicin resistance via inflammationactivated mek erk pathway findings revealed syncytin1 potential prognostic biomarker therapeutic target hccpmid34238921 doi101038 s41420021005625,0.0
exogenous copper exposure causing clinical wilson disease patient copper deficiency background human swayback disease characterized acquired copper deficiency primarily manifests myeloneuropathy common causes include malabsorptive disorders gastric surgery total parenteral nutrition excessive zinc intake contrast copper supplementation closely monitored excessive doses can lead acute intoxication chronic cases cirrhosis copper derangements rare however important consider due potential severe complicationscase presentationwe present middleaged man previously diagnosed human swayback presenting various neurological symptoms patient subsequently placed copper supplementation decade later referred hospital liver transplant evaluation due new diagnosis decompensated endstage liver disease abdominal surgery initial workup suggestive wilson diseasesubsequent atp7b gene negative ultimately patient underwent liver transplantation liver explant significant copper dry weight concentration 5436 mcg gconclusionshuman swayback rare copperrelated disease deserves awareness due potential irreversible health effects human body additionally patients require copper supplementation serial levels monitored ensure adequate copper levels,0.0
structural functional connectivity substrates cognitive impairment multiple sclerosis front neurol 2021 jul 8 12671894 doi 103389 fneur2021671894 ecollection 2021abstractcognitive impairment ci occurs 43 70 multiple sclerosis ms patients early later disease stages cognitive domains typically involved ms include attention information processing speed memory executive control growing use advanced magnetic resonance imaging mri techniques furthering understanding altered structural connectivity sc functional connectivity fc substrates ci ms regarding sc different diffusion tensor imaging dti measures eg fractional anisotropy diffusivities along tractographyderived white matter wm tracts showed relevance toward ci novel diffusion mri techniques including diffusion kurtosis imaging diffusion spectrum imaging high angular resolution diffusion imaging neurite orientation dispersion density imaging showed pathological specificity compared traditional dti require longer scan time mathematical complexities interpretation fc taskbased functional mri fmri traditionally used ms brain mapping neural activity various cognitive tasks analysis methods resting fmri seedbased independent component analysis graph analysis applied uncover functional substrates ci ms revealing adaptive maladaptive mechanisms functional reorganization relevance ci ms scfc relationships reflecting common pathogenic mechanisms wm gray matter recently explored novel mri analysis methods review summarizes recent advances mri techniques sc fc potential provide deeper understanding pathological substrates ci mspmid34305785 pmcpmc8297166 doi103389 fneur2021671894,0.0
estrategia para el seguimiento multidisciplinario pacientes con esclerosis mltiple backgroundhealth promotion can interpreted new path strategy philosophy different way thinking acting achieve health peoples multiple sclerosis neurological demyelinating disease requires longterm followup systematic character greater competitiveness medical care achieve perceived quality life patientsobjectiveto design strategy multidisciplinary followup patients multiple sclerosis aimed increasing perceived quality lifemethodsa development investigation carried neurology service arnaldo milin castro clinicalsurgical university hospital villa clara province may 2017 may 2019 theoretical methods used inductivedeductive analyticalsynthetic historical logical empirical ones documentary analysis direct observation structured interview focal group members work team patients addition investigative techniquesresultsthere shortcomings multidisciplinary followup patients human resources trained management used strategy developed assessed expert criteria contains action plan guarantee functioning multidisciplinary consultation application followup programconclusionsthe designed strategy aimed training patient responsible active selfcare strengthening capacities work team achieve objective rated adequate expert criteriamesh quality life strategies health promotion multiple sclerosis education medical,1.0
effects steam sterilization reduction fungal colony forming units cannabinoids terpene levels medical cannabis inflorescences sci rep 2021 jul 7 11 1 13973 doi 101038 s4159802193264yabstractmedical cannabis mc production rapidly expanding industry past ten years many additional phytocannabinoids discovered used different purposes mc reported beneficial treatment variety clinical conditions analgesia multiple sclerosis spinal cord injuries tourettes syndrome epilepsy glaucoma parkinson disease yet still major lack research knowledge related mc plant diseases pre postharvest stages many fungi infect mc aspergillus penicillium spp capable producing mycotoxins carcinogenic otherwise harmful consumed especially patients suffer weakened immune system causing invasive contamination humans therefore strict limits regarding permitted levels fungal colony forming units cfu commercial mc inflorescences furthermore strict regulation pesticide appliance application mc cultivation exacerbates problem order meet permitted cfu limit levels need pesticidefree postharvest treatments relying natural nonchemical methods thus decontamination approach required will damage significantly alter chemical composition plant product research new method sterilization mc inflorescences reduction fungal contaminantstes assessed without affecting composition plant secondary metabolites inflorescences exposed short pulses steam 10 15 20 s exposure cfu levels plant chemical compositions pre posttreatment evaluated steam treatments effective reducing fungal colonization detection limits effect treatments terpene profiles minor resulting mainly detection certain terpenes present untreated control steaming decreased cannabinoid concentrations treatment prolonged although insignificantly results indicate steam sterilization method tested exposure periods effective reducing cfu levels preserving initial molecular biochemical composition treated inflorescencespmid34234177 doi101038 s4159802193264y,0.0
tnfr1 antagonist atrosimab therapeutic mouse models acute chronic inflammation front immunol 2021 jul 7 12705485 doi 103389 fimmu2021705485 ecollection 2021abstracttherapeutics block tumor necrosis factor tnf thus activation tnf receptor 1 tnfr1 tnfr2 clinically used treat inflammatory diseases rheumatoid arthritis inflammatory bowel disease psoriasis however tnfr1 tnfr2 work antithetically balance immune responses involved inflammatory diseases particular tnfr1 promotes inflammation tissue degeneration whereas tnfr2 contributes immune modulation tissue regeneration therefore developed monovalent antagonistic antitnfr1 antibody derivative atrosimab selectively block tnfr1 signaling leaving tnfr2 signaling unaffected describe atrosimab highly stable different storage temperatures demonstrate therapeutic efficacy mouse models acute chronic inflammation including experimental arthritis nonalcoholic steatohepatitis nash experimental autoimmune encephalomyelitis eae data support hypothesis sufficient block tnfr1 signaling leaving immune modulatory regenerative responses via tnfr2 intact induce therapeutic effects collectively demonstrate therapeutic potential human tnfr1 antagonist atrosimab treatment chronic inflammatory diseasespmid34305946 pmcpmc8294390 doi103389 fimmu2021705485,1.0
anticd52 therapy multiple sclerosis update covid era immunotargets ther 2021 jul 7 10237246 doi 102147 itts240890 ecollection 2021abstractcd52 small surface glycoprotein composed 12 amino acids cd52 found mostly surface mature immune cells lymphocytes monocytes eosinophils dendritic cells well male genital tract within epididymis surface mature sperm low cd52 expression also found neutrophils cd52 function fully understood although experiments anticd52 antibodies shown cd52 essential lymphocyte transendothelial migration may contribute costimulation cd4+ t cells tcell activation proliferation although knowledge exact cd52 function still poor cd52 presence surface broad spectrum immune cells makes therapeutic target especially immunomediated diseases multiple sclerosis multiple sclerosis alemtuzumab registered adult patients relapsingremitting form disease defined clinical imaging features despite high efficacy drug main issue safety main adverse effects alemtuzumab associated drug infusion due cytokine release cytotoxic effects antibodies associated lymphocyte depletion leads immunosuppression secondary autoimmunity may effect excessive bcell repopulation cancer review presents current knowledge drugs mechanism action efficacy safety data clinical trials realworld observations including available though scarce data using alemtuzumab covid erapmid34268256 pmcpmc8273745 doi102147 itts240890,0.0
stem cell therapies autoimmune hepatitis abstractautoimmune hepatitis chronic inflammatory hepatic disorder may cause liver fibrosis appropriate treatment autoimmune hepatitis therefore important adult stem cells investigated therapies variety disorders latest years hematopoietic stem cells hscs first known adult stem cells ascs can give rise cell types blood immune system originally hsc transplantation served therapy hematological malignancies recently researchers found treatment positive effects autoimmune diseases multiple sclerosis mesenchymal stem cells mscs ascs can extracted different tissues bone marrow adipose tissue umbilical cord dental pulp mscs interact several immune response pathways either direct celltocell interactions secretion soluble factors characteristics make mscs potentially valuable therapy autoimmune diseases asc ascderived exosomes investigated therapy autoimmune hepatitis review aims summarize studies focused effects ascs products autoimmune hepatitis,0.0
piezo1 channels restrain regulatory t cells dispensable effector cd4+ t cell responses sci adv 2021 jul 7 7 28 eabg5859 doi 101126 sciadvabg5859 print 2021 julabstractt lymphocytes encounter complex mechanical cues immune response mechanosensitive ion channel piezo1 drives inflammatory responses bacterial infections wound healing cancer however role helper t cell function remains unclear animal model multiple sclerosis experimental autoimmune encephalomyelitis eae found mice genetic deletion piezo1 t cells showed diminished disease severity unexpectedly piezo1 essential lymph node homing interstitial motility ca2+ signaling t cell proliferation differentiation proinflammatory t helper 1 th1 th17 subsets however piezo1 deletion t cells resulted enhanced transforming growth factor tgf signaling expanded pool regulatory t treg cells moreover mice deletion piezo1 specifically treg cells showed significant attenuation eae results indicate piezo1 selectively restrains treg cells without influencing activation events effector t cell functionspmid34233878 doi101126 sciadvabg5859,0.0
clinical outcomes patients multiple sclerosis treated ocrelizumab us community ms center observational study bmj neurol open 2021 jul 7 3 2 e000108 doi 101136 bmjno2020000108 ecollection 2021abstractbackground monitor longterm outcomes ocrelizumab treatmentobjective evaluate safety treatment outcomes ocrelizumab communitybased multiple sclerosis ms populationmethods adult patients ms prescribed ocrelizumab eligible chart reviews conducted start ocrelizumab treatment every 6 months thereafterresults 355 patients enrolled 719 female mean sd age 518 125 years 783 relapsing ms rms median baseline expanded disability status scale edss iqr 30 2040 rms 65 6075 secondary progressive ms 65 6070 primary progressive ms respiratory infections occurred 401 urinary tract infections 331 patients difference percentage infections among patients 55 685 n122 55 age 675 n104 p094 twentyfive hospitalisations due infections 692 patients 55 mean edss 57 186 four patients died serum igm igg levels predict infection risk annualised relapse rate 034 patients rms preceding 2 years 009 patients received 2 ocrelizumab 600 mg courses first ontreatment mri stable 262 900 patients 69 new t2 lesions 27 enlarging t2 lesions 14 gadoliniumenhancing lesions median edss 12 months unchangedconclusion ocrelizumab effectively controlled relapse risk disability worsening although 121 patients discontinued ocrelizumab infections resulting hospitalisation concern especially older disabled patientspmid34308352 pmcpmc8264886 doi101136 bmjno2020000108,0.0
small heterodimer partner shp aggravates er stress parkinsons diseaselinked lrrk2 mutant astrocyte regulating xbp1 sumoylation background endoplasmic reticulum er stress common feature parkinsons disease pd several pdrelated genes responsible er dysfunction recent studies suggested lrrk2g2019s pathogenic mutation pdassociated gene lrrk2 cause er dysfunction thereby contribute development pd remains unclear however mutant lrrk2 influence er stress control cellular outcome study identified mechanism lrrk2g2019s accelerates er stress cell death astrocytesmethodsto investigate changes er stress response genes treated lrrk2wild type lrrk2g2019s astrocytes tunicamycin er stressinducing agent performed gene expression profiling microarrays xbp1 sumoylation pias1 ubiquitination performed using immunoprecipitation assay effect astrocyte neuronal survival assessed astrocytesneuron coculture slice culture systems provide vivo proofofconcept approach measured er stress response mouse brainresultsmicroarray gene expression profiling revealed lrrk2g2019s decreased signaling xbp1 key transcription factor er stress response increasing apoptotic er stress response typified perk signaling lrrk2g2019s astrocytes transcriptional activity xbp1 decreased pias1mediated sumoylation intriguingly lrrk2gs stabilized pias1 increasing level small heterodimer partner shp negative regulator pias1 degradation thereby promoting xbp1 sumoylation shp depleted xbp1 sumoylation cell death reduced addition identified agents can disrupt shpmediated xbp1 sumoylation may therefore therapeutic activity pd caused lrrk2g2019s mutationconclusionour findings reveal novel regulatory mechanism involving xbp1 lrrk2g2019s mutant astrocytes highlight importance shp pias1 xbp1 axis pd models findings provide important insight basis correlation mutant lrrk2 pathophysiological er stress pd suggest plausible model explains connection,0.0
end life multiple sclerosis disability causes place death among cases diagnosed 1981 2010 pirkanmaa hospital district western finland abstractbackgroundmortality risk causes death widely studied ms surveys conditions related approaching death conducted finlandobjectiveour aim sort possible needs end life eol care ms examining causes place death level hospitalization age ms related disability approaching deathmaterialsdata included information ms patients diagnosed 1981 2010 finnish university hospital district information place causes death care prior death based death certificates statistics finland decedents initial disease course disease modifying treatment dmt use ms related disability status using edss achieved hospital recordsresultsdata included 113 decedents level disability showed edss 60 higher 54 patients relapsing onset ms n 93 80 dmts used 11 infections respiratory main immediate cause death 513 n 58 among cases varying disability central university hospital 425 community hospital ward 283 places death majority cases nursing home 133 home 97 hospice 37 less often place death significantly differ agegroups chi square p086 mean age death 57 years range 2890 sd 1386 cardiovascular causes death reported mainly age group 60 years suicide age group younger 50 yearsconclusionthe level hospitalization high end life agegroups high ms related disability immobility among decedents likely relates infections common cause death along earlier surveys field showed places death level disability death share similarities younger older age groups highlighting need palliative care end life care plans ms patients triggers poor survival recently published consensus definition featuring palliative care guideline ms aimed improving end life care ms results point need future studies order assess impact palliative care treatment guidelines ms,0.0
biomarkers systemic inflammation soluble il2r multiple sclerosisassociated il2ra snp rs2104286 healthy subjects multiple sclerosis patients abstractsoluble interleukin2 il2 receptor sil2r antagonizes il2 signaling involved pathogenesis several immunemediated diseases including multiple sclerosis ms level sil2r affected msassociated single nucleotide polymorphism snp rs2104286by use elisa electrochemiluminescence investigated 26 biomarkers systemic inflammation associated sil2r rs2104286 cohorts healthy subjects ms patients serum heparin plasmawe found sil2r significantly correlated level tumor necrosis factor tnf r0391 p0002 healthy subjects association validated separate cohort additional healthy subjects confirmed previous report indicating creactive protein crp correlates sil2r r0278 p0034 none biomarkers systemic inflammation significantly associated sil2r ms patients furthermore msassociated snp rs2104286 significantly associated biomarkers systemic inflammation neither healthy subjects ms patientswe conclude sil2r associated tnf crp healthy subjects however research required confirm use sil2r biomarker systemic inflammation well assess mechanism underlying observed correlation levels sil2r tnf,0.0
cybernic treatment wearable cyborg hybrid assistive limb hal improves ambulatory function patients slowly progressive rare neuromuscular diseases multicentre randomised controlled crossover trial efficacy safety ncy3001 background rare neuromuscular diseases spinal muscular atrophy spinal bulbar muscular atrophy muscular dystrophy charcotmarietooth disease distal myopathy sporadic inclusion body myositis congenital myopathy amyotrophic lateral sclerosis lead incurable amyotrophy consequent loss ambulation thus far therapeutic approaches successful recovering ambulatory ability thus aim trial evaluate efficacy safety cybernic treatment wearable cyborg hybrid assistive limb hal lower limb type improving ambulatory function patients resultswe conducted openlabel randomised controlled crossover trial test hal nine hospitals march 6 2013 august 8 2014 eligible patients older 18 years diagnosis neuromuscular disease specified unable walk 10 m independently neither respiratory failure rapid deterioration gait primary endpoint distance passed twominute walk test 2mwt secondary endpoints walking speed cadence step length 10m walk test 10mwt muscle strength manual muscle testing mmt series functional measures adverse events failures problems errors hal also evaluated thirty patients randomly assigned groups b group 15 receiving treatments crossover design efficacy 40min walking program performed nine times compared hal plus hoist hoist final analysis included 13 11 patients groups b respectively cybernic treatment hal resulted 10066 significantly improved distance 2mwt 95 confidence interval 066719464 p 00369 compared hoist treatment among secondary endpoints total scores mmt cadence 10mwt ones showed significant improvement adverse effects slight mild myalgia back pain contact skin troubles easily remedied conclusionshal new treatment device walking exercise proven effective conventional method patients incurable neuromuscular diseasestrial registration jmactr jmaiia00156,0.0
new insights multiple sclerosis mechanisms lipids track control inflammation neurodegeneration int j mol sci 2021 jul 7 22 14 7319 doi 103390 ijms22147319abstractmultiple sclerosis ms central nervous system disease complex pathogenesis including two main processes immunemediated inflammatory demyelination progressive degeneration axonal loss despite recent progress understanding management ms availability sensitive specific biomarkers processes well neuroprotective therapeutic options targeted progressive phase disease still sought given abundance myelin sheath lipids believed play central role underlying immunopathogenesis ms seem promising subject investigation field basis previous research review literature discuss current understanding lipidrelated mechanisms involved active relapse remission progression ms insights highlight potential usefulness lipid markers prediction monitoring course ms particularly progressive stage still insufficiently addressed furthermore raise hope new effective stagespecific treatment options involving lipids targets carriers therapeutic agentspmid34298940 doi103390 ijms22147319,1.0
cd8 t cellepsteinbarr virusb cell trialogue central issue multiple sclerosis pathogenesis front immunol 2021 jul 7 12665718 doi 103389 fimmu2021665718 ecollection 2021abstractthe cause pathogenic mechanisms leading multiple sclerosis ms chronic inflammatory disease central nervous system cns still scrutiny last decade awareness increased multiple genetic environmental factors act concert modulate ms risk likewise landscape cells adaptive immune system believed play role ms immunopathogenesis expanded including cd4 t helper cells also cytotoxic cd8 t cells b cells key cellular players identified main challenge define precisely act interact induce neuroinflammation neurodegenerative cascade ms cd8 t cells implicated ms pathogenesis since 80s shown cd8 t cells predominate ms brain lesions interest role cd8 t cells ms revived 2000 years thereafter studies showing cnsrecruited cd8 t cells clonally expanded memory effector phenotype indicating situ antigendriven reactivation association certain mhc class alleles ms genetic risk implicates cd8 t cells disease pathogenesis moreover experimental studies highlighted detrimental effects cd8 t cell activation neural cells antigens responsible t cell recruitment activation cns remain elusive high efficacy bcell depleting drugs ms growing number studies implicate b cells epsteinbarr virus ebv blymphotropic herpesvirus strongly associated ms activation pathogenic t cells article reviews results human studies contributed elucidate role cd8 t cells ms immunopathogenesis discusses light current understanding autoreactivity bcell ebv involvement ms mechanism action different ms treatments based available evidences immunopathological model ms proposed entails persistent ebv infection cnsinfiltrating b cells target dysregulated cytotoxic cd8 t cell response causing cns tissue damagepmid34305896 pmcpmc8292956 doi103389 fimmu2021665718,0.0
impact covid19 pandemic hospitalizations plasmapheresis therapy multiple sclerosis neuromyelitis optica spectrum disorder nationwide analysis germany ther adv neurol disord 2021 jul 7 1417562864211030656 doi 101177 17562864211030656 ecollection 2021abstractbackground many countries worldwide reported side effects coronavirus disease 2019 covid19 pandemic influenced care patients diseases acute elective settings patients multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd represent major patient population suffering autoimmune inflammatory demyelinating disease central nervous system aimed analyze ms nmosd hospitalizations application plasmapheresis therapy dynamic different periods covid19 pandemic germanymethods conducted nationwide retrospective crosssectional study using administrative database hospitalized patients main diagnosis ms nmosd including information application plasmapheresis therapy included fullyear data 1463 hospitals ms nmosd patients hospitalized 2019 2020 germany n 87 453 compared case numbers plasmapheresis therapy rates different pandemic periods 2020 corresponding periods 2019results observed substantial decline ms nmosd patients hospitalizations different pandemic periods remarkable decline first wave pandemic first diagnosis ms 168 relapsingremitting ms 340 secondary progressive ms 489 primary progressive ms 438 nmosd 192 treatment rates plasmapheresis increased ms nmosd patients 2020 compared 2019 18 versus 16 p 0003 140 versus 93 p 0001 substantial increase first wave pandemic especially nmosd patients 197 versus 84 p 0001 conclusion marked decline ms nmosd patients hospitalizations different pandemic periods 2020 substantial reduction pandemics first wave progressive ms patients ms nmosd patients needed rescue relapse treatment continued receive plasmapheresis therapy germanypmid34285719 pmcpmc8267031 doi101177 17562864211030656,1.0
ion channels new attractive targets improve remyelination processes brain int j mol sci 2021 jul 6 22 14 7277 doi 103390 ijms22147277abstractmultiple sclerosis ms demyelinating disease central nervous system cns characterized neuroinflammation oligodendrocyte progenitor cells opcs cycling cells developing adult cns demyelinating conditions migrate site lesions differentiate mature oligodendrocytes remyelinate damaged axons however process fails disease chronicization due impaired opc differentiation moreover opcs crucial players neuroglial communication receive synaptic inputs neurons express ion channels neurotransmitter neuromodulator receptors control maturation ion channels recognized attractive therapeutic targets indeed ligandgated voltagegated channels can found among top five pharmaceutical target groups fdaapproved agents modulation ameliorates symptoms ms improves outcome related animal models however exact mechanism action ionchannel targeting compounds often still unclear due wide expression channels neurons glia infiltrating immune cells present review summarizes recent findings field get insights physiopathophysiological processes possible therapeutic mechanisms drug actionspmid34298893 doi103390 ijms22147277,1.0
validity observational evidence putative risk protective factors appraisal 3744 metaanalyses 57 topics background validity observational studies metaanalyses contested aimed appraise thousands metaanalyses observational studies using prespecified set quantitative criteria assess significance amount consistency bias evidence also aimed compare results metaanalyses observational studies metaanalyses randomized controlled trials rcts mendelian randomization mr studiesmethodswe retrieved pubmed last update november 19 2020 umbrella reviews including metaanalyses observational studies assessing putative risk protective factors regardless nature exposure health outcome extracted information 7 quantitative criteria reflect level statistical support amount data consistency across different studies hints pointing potential bias criteria level statistical significance precategorized according 106 0001 005 pvalue thresholds sample size statistical significance largest study 95 prediction intervals betweenstudy heterogeneity results tests small study effects excess significanceresults3744 associations 57 umbrella reviews assessed median number 7 interquartile range 4 11 observational studies eligible associations statistically significant p 005 611 2289 3744 26 associations p 106 1000 cases 20 000 participants continuous factors p 005 largest study 95 prediction interval excluding null large betweenstudy heterogeneity small study effects excess significance across 57 topics large heterogeneity observed proportion associations fulfilling various quantitative criteria quantitative criteria mostly independent one another across 62 associations assessed rcts observational studies 371 effect estimates opposite directions 435 effect estimates differing beyond chance two designs across 94 comparisons assessed mr observational studies discrepancies occurred 308 547 respectivelyconclusionsacknowledging goldstandard exists judge whether observational association genuine statistically significant results common observational studies rarely convincing corroborated randomized evidence,0.0
breast cancer survival multiple sclerosis matched cohort study neurology 2021 may 19101212 wnl0000000000012127 doi 101212 wnl0000000000012127 online ahead printabstractobjective tested hypotheses overall survival cancerspecific survival breast cancer diagnosis lower persons multiple sclerosis ms compared persons without ms using retrospective matched cohort designmethods applied validated case definition populationbased administrative data manitoba ontario canada identify female ms cases linked ms cohorts cancer registries identify women breast cancer selected 4 breast cancer controls without ms matched birth year cancer diagnosis year region compared allcause survival cohorts using cox proportional hazards regression adjusting age cancer diagnosis cancer diagnosis period income quintile region elixhauser comorbidity score compared cancerspecific survival cohorts using multivariable causespecific hazards model pooled findings provinces using metaanalysisresults included 779 ms cases 3116 controls breast cancer subjects stage data 1976 2822 700 diagnosed stage ii breast cancer mean sd age diagnosis 578 107 years adjustment covariates ms associated 28 increased hazard allcause mortality hazard ratio hr 128 95ci 108153 associated altered cancerspecific survival hr 098 95ci 065146 conclusion women ms lower allcause survival breast cancer diagnosis women without ms future studies confirm findings populations identify msspecific factors associated worse prognosispmid34011575 doi101212 wnl0000000000012127,0.0
impact adherence diseasemodifying therapies functional outcomes veterans multiple sclerosis j cent nerv syst dis 2021 jul 6 1311795735211028769 doi 101177 11795735211028769 ecollection 2021abstractbackground patients adhere dmts lower rate msrelated relapses disabilityobjective sought determine adherence rate diseasemodifying therapies dmts impact functional outcome s veterans multiple sclerosis ms method reviewed electronic records 279 veterans ms periodically followed ms clinic compared 3 groups patients defined according adherence dmts nonadherent poorly adherent adherent effect disability progression time sustained edss score 6results 148 53 veterans ms nonadherent dmt medication s 131 47 veterans taking medications 118 42 good 13 5 pooradherence mean age ms onset 366 112 mean duration ms sample 24 135 years mean initial edss tfim scores 409 29 sd 104 257 study sample change mmse tfim scores time sustained edss score 6 significantly favored good compared nonadherence group p 01 conclusion study suggests veterans ms adhered dmts less decline msrelated cognition disease severity disability compared non poorlyadherent groups even adjusting age gender ms duration type time edss score 6 significantly prolonged goodadherence grouppmid34285626 pmcpmc8264741 doi101177 11795735211028769,0.0
rare manifestations malignancies tuberous sclerosis complex findings tuberous sclerosis registry increase disease awareness tosca background tuberous sclerosis complex tsc rare multisystem autosomal dominant disorder caused pathogenic variants either tsc1 tsc2 gene common manifestations tsc grouped major minor clinical diagnostic criteria assessed clinical routine workup however case studies point towards existence rare disease manifestations potential association tsc malignant tumors study sought characterize rare manifestations malignancies using large cohort patientsmethodstuberous sclerosis registry increase disease awareness tosca multicenter international disease registry collecting clinical manifestations characteristics patients tsc retrospectively prospectively report rates characteristics rare manifestations malignancies patients tsc enrolled tosca registry also examined manifestations age sex genotype tsc1 tsc2 resultsoverall 2211 patients tsc enrolled study rare manifestations reported 382 173 study participants malignancies 65 29 rare manifestations frequent bone sclerotic foci 395 scoliosis 23 thyroid adenoma 55 adrenal angiomyolipoma 45 hemihypertrophy pancreatic neuroendocrine tumors pnet 31 rare manifestations commonly observed adults children 662 vs 227 females versus males 584 vs 416 except scoliosis 489 vs 511 tsc2 versus tsc1 670 vs 211 except thyroid adenoma 429 vs 571 65 individuals reported malignancies common renal cell carcinoma 477 followed breast 108 thyroid cancer 92 although malignancies common adult patients 261 reported children 631 individuals 40 years tsc1 mutations overrepresented individuals malignancies compared overall tosca cohort 321 vs 185 conclusionrare manifestations observed significant proportion individuals tsc recommend examination rare manifestations tsc collectively malignancies infrequent findings cohort however compared general population malignant tumors occurred earlier age tumor types common,0.0
factors associated functioning health relation home rehabilitation sweden nonrandomized prepost intervention study background home rehabilitation growing rehabilitation service many countries scientific knowledge components outcomes still limited aim study investigate 1 changes functioning selfrated health identified relation home rehabilitation program population communitydwelling citizens 2 sociodemographic factors health conditions home rehabilitation interventions associated change functioning selfrated health home rehabilitation programmethodthe sample consisted participants municipal home rehabilitation project sweden consisted 165 communitydwelling citizens general linear models anova repeated measures used identifying changes rehabilitation outcomes logistic regressions analysis used investigate associations rehabilitation outcomes potential factors associated outcomeresultoverall improvements functioning selfrated health found home rehabilitation program higher frequencies training sessions occupational therapists length home rehabilitation orthopaedic conditions upper extremities spine main health condition associated rehabilitation outcomesconclusionthe result indicates duration home rehabilitation interventions intensity occupational therapy well main medical condition may impact outcomes home rehabilitation needs considered planning programs however research needed guide practice policymaking,0.0
case combined central peripheral demyelination associated antineurofascin 155 antibodies paternal history multiple sclerosis neurologist 2021 jul 6 26 4 156159 doi 101097 nrl0000000000000313abstractintroduction combined central peripheral demyelination ccpd term used describe rare condition involving demyelinating lesions central peripheral nervous system etiology remains unclear pathogenic role cellmediated humoral immunity proposed number patients ccpd positive antineurofascin antinf antigalactocerebroside antilactosylseramide antibodies relation ccpd multiple sclerosis ms unclearcase report report case 30yearold man referred evaluation episodes numbness gait impairment worsened intravenous methylprednisolone found demyelination central peripheral nervous system patient eventually diagnosed antinf 155 ccpd received multiple courses intravenous immunoglobulin without significant improvement remained stable rituximab interestingly patients father suffered mild form relapsing remitting msconclusion case emphasizes clinicians need keep mind possibility coexisting demyelination central peripheral nervous system even patients family history ms need timely diagnosis imperative since several drugs used management ms can worsen patients symptoms ccpd knowledge first reported case patient antinf 155 positive ccpd family history mspmid34190211 doi101097 nrl0000000000000313,1.0
rituximab multiple sclerosis ready regulatory approval front immunol 2021 jul 6 12661882 doi 103389 fimmu2021661882 ecollection 2021abstractdespite availability lot effective diseasemodifying drugs multiple sclerosis ms particular progressive forms still represents important unmet medical need issues terms effectiveness duration response safety patient compliance increasing body evidence randomized clinical trials realworld data suggest rituximab highly effective alternative relapsing progressive ms low discontinuation rate related good benefit risk profile good compliance date use rituximab patients multiple sclerosis accordance authorized product information offlabel use however use medicine widespread several countries cases commonly used diseasemodifying drug ms subtypes use officially recognized national regulatory authorities according specific procedures ensure equal access patients safe effective optionpmid34295328 pmcpmc8290177 doi103389 fimmu2021661882,0.0
national registry amyotrophic lateral sclerosis systematic review structuring population registries motor neuron diseases background article comprises systematic review literature aims researching analyzing frequently applied guidelines structuring national databases epidemiological surveillance motor neuron diseases especially amyotrophic lateral sclerosis als methodswe searched articles published january 2015 september 2019 online databases pubmed us national institutes healths national library medicine scopus science direct springer subsequently analyzed studies considered risk factors demographic data strategic data directing technoscientific research calibrating public health policies supporting decisionmaking managers systemic panorama alsresults2850 studies identified 2400 discarded satisfying inclusion criteria 435 duplicated published books conferences hence 15 articles elected applying quality criteria selected six studies compose review researches featured registries american 3 european 2 oceania 1 continent studies specified methods data capture patients recruitment process registersdiscussionsfrom analysis selected papers reported models noticeable studies focused prospect obtaining data characterize research epidemiological studies demographic data id01 present registries representing main collected data category furthermore general health history id02 present 50 registries analyzed characteristics access control confidentiality data curation observed 50 registries comprise patientfocused webbased selfreport systemconclusionthe development robust interoperable secure electronic registries generate value research patients presents solution challenge systematic review demonstrated success population register requires actions welldefined development methods well involvement various actors civil society,0.0
dysregulated copper transport multiple sclerosis may cause demyelination via astrocytes proc natl acad sci u s 2021 jul 6 118 27 e2025804118 doi 101073 pnas2025804118abstractdemyelination key pathogenic feature multiple sclerosis ms evaluated astrocyte contribution myelin loss focused neurotrophin receptor trkb whose upregulation astrocyte finely demarcated chronic demyelinated areas ms paralleled neurotrophin loss mice lacking astrocyte trkb resistant demyelination induced autoimmune toxic insults demonstrating trkb signaling astrocytes fostered oligodendrocyte damage vitro ex vivo approaches highlighted astrocyte trkb supported scar formation glia proliferation even absence neurotrophin binding indicating trkb transactivation response inflammatory toxic mediators notably neuropathological studies demonstrated copper dysregulation ms model lesions trkbdependent expression copper transporter ctr1 glia cells neuroinflammation vitro experiments evidenced trkb critical generation glial intracellular calcium flux ctr1 upregulation induced stimuli distinct neurotrophins events led copper uptake release astrocyte turn resulted oligodendrocyte loss collectively data demonstrate pathogenic demyelination mechanism via astrocyte release copper open possibility restoring copper homeostasis white matter therapeutic target mspmid34183414 doi101073 pnas2025804118,1.0
association central hypersomnia fatigue patients multiple sclerosis polysomnographic study neurology 2021 apr 30101212 wnl0000000000012120 doi 101212 wnl0000000000012120 online ahead printabstractobjective evaluate sleepiness central hypersomnia multiple sclerosis ms associated fatigue performed long term polysomnography ms patients healthy controlsmethods patients ms healthy controls completed questionnaires sleep fatigue sleepiness depression underwent nocturnal polysomnography multiple sleep latency tests bed rest 24hour polysomnography patients divided 3 groups fatigue sleepiness fatigue sleepiness neither fatigue sleepiness results among 44 patients ms 19 432 fatigue sleepiness 15 34 fatigue 10 227 neither fatigue sleepiness compared 24 controls patients fatigue sleepiness higher rem sleep percentages median interquartile range 205 196247 vs 181 126206 lower arousal indexes 127 75170 vs 224 143344 shorter daytime mean sleep latencies 86 63143 vs 166 126195 min restless leg syndrome periodic leg movements sleep apnea similar frequencies groups central hypersomnia found 10 53 patients fatigue sleepiness narcolepsy type 2 n2 2 13 patients fatigue 3 30 patients neither fatigue sleepiness patients central hypersomnia younger sleepier without hypersomnia similar levels fatigue disability depression cognitive performance frequencies human leukocyte antigen dqb10602 genotype severity fatigue increased higher depression scores higher sleepiness severity lower sleep efficacyconclusion central hypersomnias frequent ms fatigue sleepiness present screening polysomnography studies recommendedpmid33931534 doi101212 wnl0000000000012120,0.0
difference source antiaqp4igg antimogigg antibodies csf patients neuromyelitis optica spectrum disorder neurology 2021 may 12101212 wnl0000000000012175 doi 101212 wnl0000000000012175 online ahead printabstractobjective elucidate differences source level intrathecal synthesis antiaquaporin4 antibodies aqp4igg antimyelin oligodendrocyte glycoprotein antibodies mogigg methods thirtyeight patients mogiggassociated disease 36 aqp4iggpositive neuromyelitis optica spectrum disorders nmosd studied antibody titers sera cerebrospinal fluids csf simultaneously collected acute attacks quotients csf serum levels albumin total igg diseasespecific antibody calculated intrathecal production level diseasespecific antibody evaluated calculating antibody index quotientsresults eleven 38 patients mogigg positive antibody csf patient aqp4igg showed csfrestricted aqp4igg bloodbrain barrier compromise shown raised albumin quotients seen 750 mogiggpositive cases 438 aqp4iggpositive cases moreover mogigg quotients 10 times higher aqp4igg quotients effect size r 0659 p 00001 elevated antibody index 40 confirmed 12 21 mogigg whereas seen one 16 aqp4igg 0528 p 00001 csf mogigg titers rho +0519 p 0001 antibody indexes mogigg rho +0472 p 0036 correlated csf cell counts clinical disabilityconclusions intrathecal production mogigg may occur frequently aqp4igg finding implies different properties bcell trafficking antibody production mogiggassociated disease aqp4iggpositive nmosdpmid33980704 doi101212 wnl0000000000012175,1.0
infectious diseaseassociated encephalopathies abstractinfectious diseases may affect brain function cause encephalopathy even pathogen directly infect central nervous system known infectious diseaseassociated encephalopathy systemic inflammatory process may result neuroinflammation glial cell activation increased levels cytokines reduced neurotrophic factors bloodbrain barrier dysfunction neurotransmitter metabolism imbalances neurotoxicity behavioral cognitive impairments often occur late course even though infectious diseaseassociated encephalopathies may cause devastating neurologic cognitive deficits concept infectious diseaseassociated encephalopathies still underinvestigated knowledge underlying mechanisms may distinct encephalopathies noninfectious cause still limited review focus pathophysiology encephalopathies associated peripheral sepsis malaria influenza covid19 emerging therapeutic strategies role neuroinflammationgraphic abstract,0.0
teaching video neuroimages infratentorial multiple sclerosis relapse presenting continuous hemifacial myokymia neurology 2021 apr 26101212 wnl0000000000012052 doi 101212 wnl0000000000012052 online ahead printno abstractpmid33903193 doi101212 wnl0000000000012052,0.0
onset symptom clusters multiple sclerosis characteristics comorbidities risk factors front neurol 2021 jul 6 12693440 doi 103389 fneur2021693440 ecollection 2021abstractbackground multiple sclerosis ms symptoms expected aggregate specific patterns across different stages disease studied clustering onset symptoms examined characteristics comorbidity patterns associations potential risk factors methods data stem swiss multiple sclerosis registry prospective study including 2 063 participants november 2019 ms onset symptoms clustered using latent class analysis lca latent classes examined using information sociodemographic characteristics msrelated features potential risk factors comorbid diseases results lca model six classes frequencies ranging 12 24 selected analyses latent classes comprised multiple symptoms class high probabilities across several symptoms contrasting two classes solitary onset symptoms vision problems paresthesia two gait classes emerged extremes gaitbalance class gaitparalysis class last class fatigueweaknessclass also accompanied depression symptoms memory gastrointestinal problems moderate variation sex ms types multiple symptoms class yielded increased comorbidity autoimmune disorders similar fatigueweakness class multiple symptoms class showed associations angina skin diseases migraine lifetime prevalence smoking mononucleosis frequently reported fatigueweakness paresthesia class familial aggregation differ among classes conclusions clustering ms onset symptoms provides new perspectives heterogeneity ms clusters comprise different potential risk factors comorbidities point toward different risk mechanismspmid34295301 pmcpmc8290323 doi103389 fneur2021693440,0.0
multiple cardiac rhabdomyomas associated tuberous sclerosis dizygotic twins case report background rhabdomyomas comprise majority cardiac tumors fetuses found association tuberous sclerosis complex 90 fetuses neonates multiple cardiac rhabdomyomas signs tuberous sclerosis complex however solitary cardiac rhabdomyoma cases largely unrelated tuberous sclerosis complex report case involving multiple cardiac rhabdomyomas associated tuberous sclerosis complex dizygotic twincase presentationa 36yearold japanese woman diagnosed dizygotic twin pregnancy first trimester consistent dizygosity fetal sex discordant male female 27 weeks gestation hydrops multiple echogenic cardiac masses noted male baby largest mass measuring 34 30 mm female fetus appeared normal cardiac masses enlarged gradually progression hydrops 32 weeks gestation intrauterine death male fetus confirmed next day autopsy male fetus performed cesarean section three welldemarcated whitetancolored nodules formed ventricular walls interventricular septum largest nodule 40 30 mm left ventricular wall histologically lesions diagnosed rhabdomyomasconclusionswe encountered case involving multiple cardiac rhabdomyomas arising one dizygotic twin fetuses unlike reported cases multiple cardiac rhabdomyomas case accompanied tuberous sclerosis complex best knowledge first case report multiple cardiac rhabdomyomas developed one dizygotic twins english literature,0.0
high ykl40 serum levels expression muscle tissues patients antisynthetase syndrome background protein chitinase3like1 ykl40 rarely analyzed patients myositis therefore aimed evaluate ykl40 serum levels correlate laboratory clinical parameters disease status treatment schemes analyze ykl40 expression muscle tissues patients antisynthetase syndrome assd methodsthis crosssectional singlecenter study included 64 adult patients assd age gender ethnicitymatched 64 healthy control individuals ykl40 serum levels analyzed using enzymelinked immunosorbent assay elisa kit method ykl40 expression muscle tissues analyzed using immunohistochemical technique disease status assessed using international myositis assessment clinical studies group imacs set scoresresultsthe patients mean age 448 118 years median disease duration 15 0040 years patients predominantly female 828 caucasian 734 patients stable disease median ykl40 serum level significantly higher patients assd compared healthy individuals 5384 36348531 pg ml versus 2700 20184519 pg ml respectively p 0001 however ykl40 serum levels correlate clinical laboratory disease status therapeutic parameters p 0050 except tumor necrosis factor alpha tnf serum levels spearmans correlation rho 0382 p 0007 ykl40 highly expressed inflammatory cells found muscle biopsy specimensconclusionshigh ykl40 serum levels observed patients assd correlated positively tnf serum levels moreover ykl40 expressed inflammatory cells muscle tissue,0.0
late discovering spina ventosa case report int med case rep j 2021 jul 5 14449453 doi 102147 imcrjs318003 ecollection 2021abstractintroduction spina ventosa rare condition easy misdiagnose diseases present case latediagnosed spina ventosa osteoarticular tuberculosis symptoms also severe symptoms including pleural effusion ascites anemia intensive treatment patient recovered completelycase report 7yearold boy admitted complaints painless swelling metacarpals metatarsals phalanges hands feet discharging sinus left toe family past history tuberculosis immunizations date general examination revealed child pallor emaciated lymphadenopathy detected investigations revealed hemoglobin 74 g l erythrocyte sedimentation rate esr 42 mm hour quantiferontb test positive radiograph showed irregular swelling sclerosis underlying bones righthand xray showed cortical destruction sclerosis cystic expansion right second metacarpal chest xray indicated pleural effusion histopathological examination specimen foot lung abdomen fluid confirmed tuberculosis child treated firstline tuberculosis treatment regimen isoniazid rifampicin ethambutol pyrazinamide two months followed isoniazid rifampicin pyrazinamide four months lesions disappeared six weeks intensive treatmentconclusion delay diagnosis treatment tuberculosis can lead systemic manifestations multiple organs despite delay diagnosis child good outcome due treated promptly adequately presentationpmid34262359 pmcpmc8273899 doi102147 imcrjs318003,0.0
medicinal cannabis knowledge beliefs attitudes colombian psychiatrists background use cannabinoids mental health gained strength recent years due emerging scientific evidence lifting prohibitionist laws prevailed years many countries including colombia study describes results survey colombian psychiatrists aspects medicinal cannabis attitudes towards potential use perceived knowledge beliefs surrounding regulation safetymethodswe conducted crosssectional survey 145 psychiatrists 14 territories colombia november 2019 july 2020 survey consisted 28 items topics related medicinal cannabis including attitudes clinical experience 4 items perceived knowledge 4 items indications use psychiatric pathologies 6 items indications use nonpsychiatric pathologies 8 items concerns awareness safety efficacy 6 items results summarized using descriptive statistics addition possible associations among variables examined using fishers exact testresultseightytwo percent psychiatrists agreed medical cannabis available different medical conditions 731 stated wanted able prescribe however 662 said know help patients legally access 25 understood legal status medicinal cannabis country mental health indications received highest approval levels cannabis use insomnia 352 anxiety disorders 29 agitation dementia 186 greatest disapproval cannabis use indicated schizophrenia 669 approved nonpsychiatric medical conditions cancerrelated chronic pain 876 chemotherapyrelated nausea vomiting 786 chronic pain associated cancer 724 multinomial stepwise logistic regression analysis showed female psychiatrists agree mc treat psychiatric symptoms likely agree nonpsychiatric useconclusionsour results showed sample colombian psychiatrists favorable attitude towards prescription medicinal cannabis however serious lack knowledge legal status medicinal cannabis country methods patients can gain access governmentregulated products approve use mc nonpsychiatric conditions general disapprove use mental illnesses generally consider medicinal cannabis safe treatment compared psychotropic drugs medications potential risk dependence opioids benzodiazepines,0.0
rantes ccl5 signaling jawbone cavitations epistemology multiple sclerosis research case studies degener neurol neuromuscul dis 2021 jul 5 114150 doi 102147 dnnds315321 ecollection 2021abstractbackground role played signaling pathways cellcell communication associated multiple sclerosis ms progression become critical area research chemokine rantes regulated upon activation normal tcell expressed secreted also named chemokine cc motif ligand 5 ccl5 r c protein investigated neuroinflammatory research due link ms developmentobjective research bone marrow defects jawbone bmdj morphologically presents fattydegenerative osteonecrosis jawbone fdoj presents overexpression r c signaling affected areas try elucidate potential link jawbonederived r c msmethods seventeen bmdj fdoj samples extracted 17 ms patients well samples 19 healthy controls analyzed r c expression using beadbased luminex analysis serum r c levels 10 ms patients examined bone density histology r c expression analyzed two clinical case studiesresults high r c overexpression found bmdj fdoj samples obtained ms group serum r c levels also upregulated ms group r c serum levels ms cohort higher healthy controls contrast histology bmdj fdoj samples showed inflammatory cellsdiscussion r cinduced silent inflammation ms widely discussed scientific literature along r c triggering inflammation central nervous system might key development msconclusion authors suspect bmdj fdoj may serve trigger ms progression via r c overexpression dental medical communities made aware bmdj fdoj cases mspmid34262389 pmcpmc8275106 doi102147 dnnds315321,0.0
development clinical guidelines service provision functional electrical stimulation support walking mixed method exploration stakeholder views background past 20 years functional electrical stimulation fes grown clinical use support walking people lower limb weakness paralysis due upper motor neuron lesions despite growing consensus regarding benefits provision across uk internationally variable study aimed explore stakeholder views relating value clinical guideline focusing service provision fes support walking people might use includedmethodsa mixed methods exploration sought views key stakeholders pragmatic online survey n 223 focusing study aim developed distributed email distribution list uk association chartered physiotherapists interested neurology acpin parallel qualitative service evaluation patient public involvement consultation conducted two group seven individual interviews conducted fesusers n 6 family carers n 3 physiotherapists n 4 service providers developers n 2 researchers n 1 distributors fes n 1 descriptive analysis quantitative data framework analysis qualitative data conductedresultssupport clinical guideline development clear qualitative interviews survey results survey respondents strongly endorsed possible uses clinical guideline ensuring best practice supporting people seeking access fes service data analysis synthesis provided clear areas inclusion clinical guidelines including current research evidence consensus relating likely benefit optimal service provision well pathways access specific areas investigation summarised inclusion first stage delphi consensus studyconclusionskey stakeholders believe value clinical guideline focuses different stages service provision fes support walking delphi consensus study planned based findings,1.0
traumatic brain injury results unique microglial astrocyte transcriptomes enriched type interferon response background traumatic brain injury tbi leading cause death disability lacks neuroprotective therapies following tbi secondary injury response pathways activated contribute ongoing neurodegeneration microglia astrocytes critical neuroimmune modulators early persistent reactivity following tbi although histologic glial reactivity well established precise understanding microglia astrocyte function following trauma remains unknownmethodsadult male c57bl 6j mice underwent either fluid percussion sham injury rna sequencing concurrently isolated microglia astrocytes conducted 7 days postinjury evaluate celltypespecific transcriptional responses tbi dual situ hybridization immunofluorescence used validate tbiinduced gene expression changes microglia astrocytes identify spatial orientation cells expressing genes comparative analysis performed glial transcriptomes prior reports mild tbi neurologic diseases determine severe tbi induces unique states microglial astrocyte activationresultsour findings revealed sustained lineagespecific transcriptional changes microglia astrocytes microglia showing greater transcriptional response astrocytes subacute time point microglia astrocytes showed overlapping enrichment genes related type interferon signaling mhc class antigen presentation microglia astrocyte transcriptional response severe tbi distinct prior reports mild tbi neurodegenerative neuroinflammatory diseasesconclusionconcurrent lineagespecific analysis revealed novel tbispecific transcriptional changes findings highlight importance celltypespecific analysis glial reactivity following tbi may assist identification novel targeted therapies,1.0
magnetic resonance imaging clinical features demyelinating degeneration white matter young patients int j gen med 2021 jul 5 1431773186 doi 102147 ijgms302587 ecollection 2021abstractobjective magnetic resonance imaging mri brain white matter demyelination often focuses demyelinating disease cerebral small vascular disease diagnosis followup cognitive dysfunction observation study explored mri findings clinical manifestations demyelinating degeneration white matter young patientsmethods total ninetyfour patients white matter degeneration diagnosed mri enrolled study january 2014 july 2018 patients divided two groups demyelinating disease group n 43 nondemyelinating disease group n 51 imaging findings clinical manifestations two groups analyzedresults compared nondemyelinating group female male patients demyelinating group p 005 addition 45 patients imaging result demyelinating degeneration white matter multiple sclerosis 39 patients met diagnosis multiple sclerosis 867 comparison 49 patients imaging result demyelinating degeneration white matter four patients met diagnosis demyelinating disease 82 conclusion patients complaining headaches dizziness vertigo symptoms case imaging result showing demyelinating degeneration white matter alone possibility clinical diagnosis demyelinating disease minimalpmid34262331 pmcpmc8274702 doi102147 ijgms302587,1.0
motor imagery resource fatigue rehabilitation returntowork multiple sclerosis patientsa mini systematic review front neurol 2021 jul 5 12696276 doi 103389 fneur2021696276 ecollection 2021abstractfatigue multidimensional symptom physical cognitive aspects can affect quality daily working life activities motor imagery mi represents important resource use rehabilitation processes useful among others job integration reintegration neurological pathologies multiple sclerosis ms define effective rehabilitation protocols integrate mi reduction fatigue patients ms pwms literary review performed august 2020 five articles included qualitative synthesis including two feasibility pilot randomized control trials rcts 3 rcts good quality according pedro score low risk bias according cochrane collaboration tool literature suggested mi association rhythmicauditory cues may effective rehabilitation resource reducing fatigue positive effects observed perceived cognitive psychological fatigue pwms require greater compensatory strategies healthy individuals use rhythmicauditory cues may useful optimizing cognitive processing mi acts internal stimulus enhanced made vivid outside cues findings provide evidence mi promising rehabilitation tool reducing fatigue pwms return work strategiespmid34290665 pmcpmc8287528 doi103389 fneur2021696276,0.0
fear relapse patients suffering rrms influence quality life abstractmultiple sclerosis ms chronic potentially debilitating disease affects millions patients worldwide 85 patients experience disease subtype characterised relapses remittance rrms many studies investigated factors influencing patientsnullnull healthrelated quality life hrqol rrms none taken patientsnull fear relapses account study measured patientsnull selfreported hrqol fear relapse health anxiety ha number relapses duration disease type medication perceived level side effects treating neurologists provided estimate patientsnull disease severity covariates demographic personal diseaserelated characteristics included regression modelling association hrqol model showed hrqol strongly associated disease severity estimated neurologists highly correlated number relapses disease duration however upon adjustment presence covariates association disease severity hrqol attenuated remained covariate significantly associated hrqol notably modelling also revealed significant association ha rrms patients studynulls findings important implications management ms rrms patients point critical roles ha drivers hrqol rrms given importance hrqol patient experience economically argue nuanced understanding needed subjective nature quality life determinants interventions aimed reducing psychological distress anxiety explored,0.0
pneumonia caused pseudomonas fluorescens case report background pseudomonas fluorescens p fluorescens detected respiratory samples patients however previous reports published p fluorescens cultures lung tissuescase presentationhere report case pneumonia caused p fluorescens p fluorescens identified lung biopsy specimens first time case according antibiotic susceptibility testing ast p fluorescens patient given ciprofloxacin treatment temperature patient returned normal chest ct examination revealed improvements pulmonary inflammationconclusionsthese findings suggest patients pneumonia caused p fluorescens treated timely manner according ast results,0.0
global overview genetically interpretable multimorbidities among common diseases uk biobank background multimorbidities greatly increase global health burdens landscapes genetic risks systematically investigatedmethodswe used hospital inpatient data 385 335 patients uk biobank investigate multimorbid relations among 439 common diseases postgwas analyses performed identify multimorbidity shared genetic risks genomic loci network well overall genetic architecture levels conducted network decomposition networks genetically interpretable multimorbidities detect hub diseases involved molecules functions moduleresultsin total 11 285 multimorbidities among 439 common diseases identified 46 genetically interpretable loci network overall genetic architecture levels multimorbidities affecting different physiological systems displayed different patterns shared genetic components former likely share locilevel genetic components latter likely share networklevel genetic components moreover loci networklevel genetic components shared multimorbidities converged cell immunity protein metabolism gene silencing furthermore found genetically interpretable multimorbidities tend form network modules mediated hub diseases featuring physiological categories finally showcased hub diseases mediating multimorbidity modules help provide useful insights genetic contributors multimorbiditiesconclusionsour results provide systematic resource understanding genetic predispositions multimorbidities indicate hub diseases converged molecules functions may key treating multimorbidities created online database facilitates researchers physicians browse search download multimorbidities https multimorbiditycompsysbioorg,0.0
conus medullaris involvement demyelinating disorders cns comparative study abstractbackgrounddifferentiation demyelinating disorders cns seems challenging practice conus medullaris coneshaped end spinal cord involved antimog patients based preliminary studies possibly helpful detail differentiation nevertheless evidence still limited underlying cause unclear undiscussed previous studiesobjectiveto contribute preliminary studies comparing conus involvement among patients ms antiaqp4 antimog diseases using larger sample sizemethodsmore thousand ms antiaqp4 antimog patients followed maximum five years scanned conus medullaris involvement data regarding cohort analyzed compared using statistical methodsresultsthe rate conus medullaris involvement significantly higher antimog patietns or27109 p 0001 followed antiaqp4 or4944 p0004 ms patients orreference survival analysis showed higher pace cumulative incidence conus attacks antimog patients conusinvolved patients showed significant difference regarding age sex concurrent brain lesions partial recovery predictive values show probability diagnosed antimog roughly 13 times higher conusinvolved patients 2593 vs 197 although probability still higher ms much higher incidenceconclusiondespite minor differences results line previous studies confirming higher rate conus medullaris involvement among antimog patients potential underlying causes proposed remain investigated future studies,1.0
influenza vaccine hesitancy patients multiple sclerosis monocentric observational study brain sci 2021 jul 5 11 7 890 doi 103390 brainsci11070890abstractbackground socalled vaccine hesitancy still represents common phenomenon undermines effectiveness vaccination campaigns 2020 italian medicines agency recommended bring forward flu vaccination campaign whose importance also emphasized patients multiple sclerosis ms aimed assess vaccination behavior patients ms prepare upcoming sarscov2 vaccination challengemethods observational study carried one ms clinical centre enrolled ms patients eligible flu vaccines recommended italian medicines agencyresults 194 patients enrolled patients mean age 439 years 66 female comorbidities mainly represented nonautoimmune diseases identified 52 patients almost patients receiving dmt study period mainly dimethyl fumarate natalizumab teriflunomide interferon 194 patients 582 accepted vaccinated statistically significant differences found except use natalizumab higher among vaccinated patientsconclusion results study emphasize importance education communication campaigns addressed healthcare providers patients ms especially considering ms patients currently receiving covid19 vaccinationspmid34356125 doi103390 brainsci11070890,0.0
amino terminal recognition ccr6 chemokine receptor antibody blocks ccl20 signaling il17 expression via arrestin background ccr6 chemokine receptor important target inflammatory diseases th17 cells express ccr6 number inflammatory cytokines including il17 il22 involved propagation inflammatory immune responses ccr6 antagonist potential treatment inflammatory diseases psoriasis rheumatoid arthritis aim study develop antagonistic monoclonal antibody mab human ccr6 receptor hccr6 resultswe generate monoclonal antibodies hccr6 immunizing balb c mice hccr6 overexpressing cells antibodies tested flow cytometry specific binding hccr6 cloned limiting dilution resulted isolation purification monoclonal antibody 1c6 elisa flow cytometry determined antibody obtained binds hccr6 nterminal domain ability 1c6 neutralize hccr6 signaling tested determined 1c6 antibody able block response arrestin recruitment assay ic50 1023 nm inhibit calcium mobilization addition found chemotaxis assay 1c6 reduces migration hccr6 cells ligand ccl20 finally determined rtqpcr expression il17a th17 cells treated 1c6 inhibitedconclusionsin present study applied whole cell immunization successfully obtain antibody capable neutralize hccr6 signaling reduce hccr6 cells migration il17 expression results provide efficient approach obtain therapeutic potential antibodies treatment ccr6mediated inflammatory diseases,0.0
healthrelated quality life differ people relapse onset progressive onset multiple sclerosis abstractbackgroundmultiple sclerosis ms can categorised relapse onset ms roms progressive onset ms proms aimed examine healthrelated quality life terms health state utilities hsus dimensional scores differed onset type health dimensions differences pronounced whether differences remained stratified disability severitymethodswe estimated hsus unique composite superdimensionnull individual dimensionnull scores crude age sex disease duration disease modifying therapies use adjusted stratified onset type disability severity sample 1577 participants australian ms longitudinal study using assessment quality life aqol 8dresultsadjusted mean overall hsu proms 055 007 lower roms adjusted mean physical psychosocial superdimension scores proms 051 028 007 006 lower roms respectively individual health dimensions largest difference seen independent living 012 followed relationships 007 selfworth 007 whilst hsus dimensional scores negatively associated increasing disability severity onset types estimates disability severity differ two cohortsconclusionsour study provides comprehensive assessment effects ms onset type overall disabilityseverity specific hrqol scores using detailed preferentially sensitive aqol8d instrument overall hrqol substantially lower proms roms mean hrqol values disability level differ onset type indicating future health economic models can use hsu inputs onset types,0.0
phloretin suppresses neuroinflammation autophagymediated nrf2 activation macrophages background macrophages play dual role neuroinflammatory disorders multiple sclerosis ms involved lesion onset progression can also promote resolution inflammation repair damaged tissue study investigate phloretin flavonoid abundantly present apples strawberries lowers inflammatory phenotype macrophages suppresses neuroinflammationmethodstranscriptional changes mouse bone marrowderived macrophages upon phloretin exposure assessed bulk rna sequencing underlying pathways related inflammation oxidative stress response autophagy validated quantitative pcr fluorescent absorbance assays nuclear factor erythroid 2related factor 2 nrf2 knockout mice western blot immunofluorescence experimental autoimmune encephalomyelitis eae model used study impact phloretin neuroinflammation vivo confirm underlying mechanismsresultswe show phloretin reduces inflammatory phenotype macrophages markedly suppresses neuroinflammation eae phloretin mediates effect activating nrf2 signaling pathway nrf2 activation attributed 5 ampactivated protein kinase ampk dependent activation autophagy subsequent kelchlike echassociated protein 1 keap1 degradationconclusionsthis study opens future perspectives phloretin therapeutic strategy neuroinflammatory disorders mstrial registrationnot applicable,0.0
pet therapy nonpharmacological treatment option neurological disorders review literature cureus 2021 jul 4 13 7 e16167 doi 107759 cureus16167 ecollection 2021 julabstractanimal therapy ownership studied nonpharmacologic treatment option cardiovascular psychological disorders animal companionship less studied neurological disorders stroke dementia parkinsons disease multiple sclerosis huntingtons disease epilepsy acute brain injury review examines effects emotional support dogs dog therapy dog ownership specific neurological disorders may serve nonpharmaceutical option improve patient symptoms quality life disease course articles gathered studied effect animalassisted therapy pet therapy dog ownership physical activity neurological disorders studies relating topic assessed impact neurological disorders ranged cognition mobility quality life mood improvement disease course dog therapy ownership found improve mood quality life disease symptoms across multiple neurological disorders also encouraged physical activity shown help many diseases studied even ones associated skeletal muscle apoptosis huntingtons disease dog therapy ownership safe effective nonpharmaceutical approach treating chronic progressive neurological disorderspmid34367777 pmcpmc8336327 doi107759 cureus16167,0.0
variant uncertain significance sdhaf1 succinate dehydrogenase chaperone protein adult patient spastic paraparesis leukoencephalopathy summarysuccinate dehydrogenase sdh respiratory complex ii consists four nuclearencoded subunits chaperone protein succinate dehydrogenase assembly factor 1 sdhaf1 plays essential role assembly sdh incorporation ironsulfur clusters sdhb subunit sdhb couples oxidation succinate fumarate reduction ubiquinone coenzyme q ubiquinol previously reported mutations sdhaf1 associated infantile leukoencephalopathy report adult case homozygous variant uncertain significance vus mutation sdhaf1 presenting dementia spastic paraparesis cardiomyopathy initially diagnosed multiple sclerosis,0.0
overcome barriers skin exosome therapy abstractexosomes nanosized cargos lipid bilayer structure carrying diverse biomolecules including lipids proteins nucleic acids small vesicles secreted types cells communicate since exosomes circulate bodily fluids can transfer information local cells also remote cells therefore exosomes considered potential biomarkers various treatments recently studies shown efficacy exosomes skin defects aging atopic dermatitis wounds also exosomes studied used ingredients commercialized skin treatment products review discussed need exosomes skin therapy together current challenges moreover functional roles exosomes terms skin treatment regeneration overviewed finally highlighted major limitations future perspective exosome engineering,0.0
bone marrow transfer relapsingremitting eae ameliorates disease first remission synergistic effect upon cotransplantation mesenchymal stem cells vaccines basel 2021 jul 3 9 7 736 doi 103390 vaccines9070736abstractmultiple sclerosis ms neurological disorder characterized autoimmune response demyelinating plaques axonal damage intense immunosuppression ii followed autologous hematopoietic stem cell transplantation proposed treatment severe forms ms used murine relapsingremitting rr experimental autoimmune encephalomyelitis rreae evaluate transplantation syngeneic bone marrow cells bmc ii combination mesenchymal stem cells mscs new therapeutic adjunct capable improving immune reconstitution eaeaffected mice treated bmc alone observed drastic reduction clinical course early rr phase disease difference rreae clinical course mice treated bmc alone cotransplanted mice analyze immune reconstitution quantified circulating immune cells nave rreaeaffected mice ii bmc alone combination msc although ii resulted reduced numbers circulating immune cells reconstitution differ cotransplanted mice early phase disease il4 significantly elevated cotransplanted mice compared treated bmc alone data suggest bmc transplantation ii transiently ameliorates clinical symptoms rreae cotransplantation msc synergistic effectpmid34358152 doi103390 vaccines9070736,1.0
longterm clinical mri cognitive followup large cohort pathologically confirmed predominantly tumefactive multiple sclerosis abstractbackgroundlimited studies described longterm outcomes pathology confirmed multiple sclerosis ms objectivesto describe longterm clinicalradiographiccognitive outcomes prospectively followed cohort patients pathologically confirmed cns demyelinating disease consistent msmethodssubjects underwent clinical assessment standardized 3tmri brain cognitive batteryresultsseventyfive patients included biopsied lesion size 2 cm 62 75 followup median duration since biopsy 11 years median edss 3 lesion burden large median 10 cm3 followup 57 75 met ms criteria 17 75 clinically isolated syndrome 1 radiographic changes disability scores comparable prevalence cohort olmsted county p 0001 n 218 cognitive outcomes agenormed standards included psychomotor attention working memory executive function domains total lesion volume index lesionrelated severity correlated edss cognitive performance volumetric cortical subcortical gm correlated less lesion metrics cognitive outcomesconclusiondespite early aggressive course pathologically confirmed ms longterm course comparable typical ms study cognitive impairment group seemed correlate strongest index lesion severity total lesion volume remains established aggressive nature lesion biopsy treatment affect clinical cognitive outcomes,1.0
alterations intermuscular coordination underlying isokinetic exercise stroke implications neurorehabilitation background abnormal intermuscular coordination limits motor capability strokeaffected upper limbs evaluating intermuscular coordination affected limb various biomechanical task constraints impact stroke motor control can analyzed intermuscular coordinationbased rehabilitation strategies can developed study investigated upper limb intermuscular coordination stroke isokinetic movementsmethodssixteen chronic stroke survivors eight neurologically intact individuals recruited endpoint forces electromyographic activities shoulder elbow muscles measured participants performed isokinetic upper limb movements threedimensional space intermuscular coordination stroke survivors control participants quantified form muscle synergies compared number composition activation coefficients muscle synergies endpoint force groups correlation alteration muscle synergies level motor impairment investigatedresultsfour five muscle synergies stroke control groups observed respectively composition muscle synergies comparable groups except three heads deltoid muscle coactivated formed one synergy stroke group whereas muscles formed two synergies control group number muscle synergies groups matched comparable composition muscle synergies observed groups alternatively modulation synergy activation coefficients altered stroke severity motor impairments negatively correlated similarity poststroke synergies respect mean control synergiesconclusionsstrokeaffected upper limbs seemed modularize activation shoulder elbow muscles fairly similar way neurologically intact individuals isokinetic movements compared free ie unconstrained movement exercise biomechanical constraints including isokinetic constraint might promote activation muscle synergies independently stroke survivors postulated effect biomechanical constraints intermuscular coordination suggested possible intermuscular coordinationbased rehabilitation protocol provides biomechanical constraint appropriate trainee throughout progress rehabilitation,1.0
increased rate hospitalisation covid19 among rituximabtreated multiple sclerosis patients study swedish multiple sclerosis registry abstractbackgroundthe primary objective study analyse association multiple sclerosis ms diseasemodifying therapy dmt exposure hospitalisation patients infected covid19methodsassociations ms dmt exposure covid19 hospitalisation analysed using univariable multivariableclustered propensity score weighted logistic regression models clustered individual patients control patients contributing multiple covid19 episodesfindingsas 18 january 2021 total 476 reported covid19 cases recorded ms patients swedish ms registry 292 613 confirmed covid19 mean value standard deviation sd age infection 440 years 116 292 confirmed infections 68 232 required hospitalisation total 49 164 confirmed covid19 patients rituximab baseline 299 required hospitalisation compared rate 127 dmts combined rituximab confirmed covid19 patients associated 295 times odds hospitalisation relative dmt combined odds ratio 295 95 confidence interval ci 148587 interpretationrituximab treatment known increase risk severe infections general also confers risk ms patients covid19 comparison ms dmts,0.0
gene regulatory network human gmcsfsecreting t helper cells j immunol res 2021 jul 3 20218880585 doi 101155 2021 8880585 ecollection 2021abstractgmcsf produced autoreactive cd4positive t helper cells involved pathogenesis autoimmune diseases multiple sclerosis however molecular regulators establish maintain features gmcsfpositive cd4 t cells unknown order identify regulators isolated human gmcsfproducing cd4 t cells human peripheral blood using cytokine capture assay compared cells corresponding gmcsfnegative fraction furthermore studied nave cd4 t cells memory cd4 t cells bulk cd4 t cells individuals additional control cell populations result provide rich resource integrated chromatin accessibility atacseq transcriptome rnaseq data primary human cd4 t cell subsets show identified signatures associated human autoimmune diseases especially multiple sclerosis combining information mrna expression dna accessibility predicted transcription factor binding reconstructed directed gene regulatory networks connecting transcription factors targets comprise putative key regulators human gmcsfpositive cd4 t cells well memory cd4 t cells results suggest potential therapeutic targets investigated future human autoimmune diseasepmid34285924 pmcpmc8275380 doi101155 2021 8880585,0.0
bloodbrain gutvascular barriers perspective claudins tissue barriers 2021 jun 211926190 doi 101080 2168837020211926190 online ahead printabstractin organs brain endothelial cells form robust highly selective bloodtotissue barrier however organs intestine endothelial cells provide less stringent permeability allow rapid exchange solutes nutrients needed maintain structural functional integrity highly dynamic bloodbrain gutvascular barriers endothelial cells form highly specialized cellcell junctions known adherens junctions tight junctions claudins family fourmembranespanning proteins tight junctions barrierforming poreforming properties tissuespecific expression claudins linked different diseases characterized barrier impairment review summarize recent progress field claudins particular attention expression function bloodbrain barrier recently described gutvascular barrier physiological pathological conditionsabbreviations 22q11ds 22q11 deletion syndrome ackr1 atypical chemokine receptor 1 ad alzheimer disease aqp aquaporin atp adenosine triphosphate amyloid bac bacterial artificial chromosome bbb bloodbrain barrier c ebp ccaat enhancerbinding protein camp cyclic adenosine monophosphate 3 5cyclic adenosine monophosphate cd cluster differentiation cns central nervous system dsred discosoma red eae experimental autoimmune encephalomyelitis ecv304 immortalized endothelial cell line established vein apparently normal human umbilical cord egfp enhanced green fluorescent protein esam endothelial cellselective adhesion molecule glut1 glucose transporter 1 gvb gutvascular barrier h2b histone h2b happ human amyloid precursor protein hek human embryonic kidney jacop junctionassociated coiled coil protein jam junctional adhesion molecules lyve1 lymphatic vessel endothelial hyaluronan receptor 1 madcam1 mucosal vascular addressin cell adhesion molecule 1 mapk mitogenactivated protein kinase mcao middle cerebral artery occlusion mmp metalloprotease ms multiple sclerosis mupp multipdz domain protein patj pals1associated tight junction protein pdgfr plateletderived growth factor receptor polypeptide pdgfr plateletderived growth factor receptor polypeptide rho rhoassociated protein kinase rock rhoassociated coiledcoilcontaining protein kinase rtqpcr real time quantitative polymerase chain reactions pdgfr soluble plateletderived growth factor receptor polypeptide t24 human urinary bladder carcinoma cells tg2576 transgenic mice expressing human amyloid precursor protein tnf tumor necrosis factor wtwildtype zo zonula occludenspmid34152937 doi101080 2168837020211926190,0.0
balance motion coordination parameters can improved patients type 2 diabetes physical balance training nonrandomized controlled trial background type 2 diabetes t2d cause multiple complications including retinopathy peripheral neuropathy complications well understood believed contribute gait instability poor balance control increased falling risk also reported people diabetic peripheral neuropathy dpn patients dpn increased risk falling due decreased proprioceptive feedback effective balance training improve postural control patients dpn purpose evaluation conducted balance training designedmethodsthe goal study determine values proprioception balance muscle coordination strength patients t2d analyze whether biofeedback balance training use biodex balance system improve parameters assess fall risk general stability index gsi index frontalposterior fpi mediallateral mli stability evaluated 37 patients diagnosed type 2 diabetes mellitus recruited study results compared control group consisting 41 healthy participants homogenic study group terms age body mass index bmi resultsthere statistically significant differences patients diabetes compared healthy subjects gsi 279 vs 11 fpi 166 vs 07 mli 088 vs 052 risk falling 518 vs 272 p 005 also statistically significant changes training stability indices gsi 279 vs 126 fpi 166 vs 077 mli 088 vs 054 accordingly p 005 risk falling 518 vs 387 p 005 study group undergone training biofeedbackconclusionsthis study found decreased balance motor coordination increased risk falling patients type 2 diabetes parameters improved patients undergone training programme biofeedback furthermore agedependent deprivation static balance observed along increased risk falling result increasing bmi,0.0
schizophrenia syndrome due c9orf72 mutation case report cautionary tale role hybrid brain imaging background frontal variant frontotemporal dementia common cause presenile dementia hexanucleotide expansion chromosome 9 recently recognized common genetic mutation cause illness subtype tends present psychiatrically psychosis common presenting symptom onset cognitive changes brain atrophy case series published describing prominence early psychotic symptoms lack clear brain atrophy clinical brain imaging imposing challenge reaching early accurate diagnosis report present case whereby diagnosis schizophrenia syndrome made patient treated years multiple interventions syndrome reaching accurate diagnosis frontal variant frontotemporal dementia due hexanucleotide expansion chromosome 9 diagnosis confirmed genetic testing findings hybrid positron emission tomography magnetic resonance imaging scanningcase summarya 60yearold female diagnosed schizophrenia age 50 presenting delusions hallucinations proved refractor several lines pharmacological nonpharmacological interventions including electroconvulsive therapy patient history postpartum psychosis 20s referred cognitive neurology due progressive decline function clinical structural brain imaging data adequate support alternative neurological diagnosis careful inquiry elicited history psychotic illness followed progressive decline sister genetic testing confirmed hexanucleotide expansion chromosome 9 mutation patient offered stateoftheart fdglucose positron emission tomography magnetic resonance imaging scan available centre volumetric magnetic resonance imaging scan show volume loss frontotemporal areas hybrid scan showed regionally specific deficit fdglucose positron emission tomography affecting medial superior frontal insula inferior temporal thalamus anterior cingulate cortex consistent behavioral variant frontotemporal dementiaconclusionsthis case highlights importance considering frontal variant frontotemporal dementia due hexanucleotide expansion chromosome 9 facing relatively lateonset refractory schizophrenialike syndrome careful history available sources elicit family history similar presentation important genetic testing functional brain imaging can aid confirming diagnosis potentially streamlining management cases,0.0
regulatory role local tissue signal del1 cancer inflammation review abstractdevelopmental endothelial locus1 del1 secretory multifunctional domain protein can bind integrins phosphatidylserine local tissue signal plays regulatory role cancer microenvironment inflammation del1 destructive effects cancers associated progression invasion cancers contrast del1 also plays protective role inflammation del1 regulates inflammation regulating generation neutrophils bone marrow inhibiting recruitment migration neutrophils accelerating clearance neutrophils macrophages del1 il17 reciprocally regulated balance maintains immune system homeostasis del1 expected become new therapeutic target inflammatory disorders multiple sclerosis,0.0
everolimus versus sirolimus angiomyolipoma associated tuberous sclerosis complex multiinstitutional retrospective study china abstractpurposeto evaluate efficacy safety everolimus sirolimus patients tuberous sclerosis complexassociated angiomyolipomas tscaml materials methods performed multiinstitutional retrospective study tscaml patients treated oral everolimus 10 mg sirolimus 2 mg per day least 3 months angiomyolipoma volume estimated using orthogonal measurements mri ct adverse events aes assessed according national cancer institute common terminology criteria adverse events analyses performed using spss 190 softwareresultsresponse rates high groups prolonged medication durations therapeutic efficacy agents became significant tscaml volume reduction 6 12 months pronounced patients everolimus sirolimus half patients treated everolimus 50 reduction approximately 80 30 reduction higher patients treated sirolimus regarding safety significant difference incidence aes two groupsconclusionsboth everolimus sirolimus excellent therapeutic options tscaml however everolimus better therapeutic efficacy sirolimus particularly reducing tscaml volume everolimus therefore recommended first choice therapy tscaml,0.0
performance validity outpatients multiple sclerosis cognitive complaints abstractbackgroundsuboptimal performance neuropsychological assessment renders cognitive test results invalid however suboptimal performance rarely investigated multiple sclerosis ms objectivesto investigate potential underlying mechanisms suboptimal performance msmethodsperformance validity testing neuropsychological assessments neuroimaging questionnaires analyzed 99 ms outpatients cognitive complaints based performance validity testing patients classified valid invalid performers based neuropsychological test results cognitively impaired preserved group comparisons correlational analyses performed demographics patientreported diseaserelated outcomesresultstwentypercent displayed invalid performance invalid valid performers differ regarding demographic patientreported diseaserelated outcomes disease severity invalid valid performers cognitive impairment comparable worse cognitively preserved valid performers lower performance validity scores related lower cognitive functioning lower education male higher disability levels p005 conclusionsuboptimal performance frequently occurs patients ms cognitive complaints clinical practice cognitive research suboptimal performance considered interpretation cognitive outcomes identification factors differentiate suboptimal optimal performers cognitive impairment needs exploration,0.0
cardiovascular risk estimated individuals multiple sclerosis case control study abstractbackgroundpatients multiple sclerosis ms 15fold increase cardiovascular diseases cvd mortality compared without ms therefore aim study assess cvd risk ms patients multiple cardiometabolic indexes investigate associated factorsmethodsthe ms group included 57 patients matched age sex 57 healthy controls evaluated physical activity smoking anthropometric indices blood pressure plasma biomarkers framingham risk score frs multiple cardiovascular risk indexes calculated clinical course disease age onset disease duration diseasemodifying therapy relapse rate edss physical functional impairment investigatedresultsthe mean age 346 years old majority 895 ms group rrms clinical course mild level disability edss10 wc p0022 fm p0007 different ms control groups frs higher ms group 10 versus 0 related high prevalence dyslipidemia 438 versus 368 atherogenic index plasma aip 0013 castelli risk indexes crii p0017 ii criii p0008 nonhdlc p0044 higher ms groupconclusionms patients controlled disease course higher cardiovascular risk comparable healthy individuals emphasize use frs monitoring crii ii well aip important lipid markers manage cvd risk individuals ms,0.0
clinicopathological characteristics patients paraproteinemia renal damage background study aimed analyze clinicopathological characteristics patients paraproteinemia renal damagemethodsninetysix patients 2014 2018 paraproteinemia renal damage enrolled clinical data renal pathology treatment prognosis data collectedresultsa total 96 patients 54 male 42 female accounting 27 renal biopsies enrolled study among 42 monoclonal gammopathy renal significance mgrs 21 renal monotypic immunoglobulin alone renal monoig 19 monoclonal gammopathy undetermined significance mgus individuals multiple myeloma mm accounted fewest number patients n 14 mgrs group main diseases amyloidosis n 25 cryoglobulinemic glomerulonephritis n 7 mm group main diseases cast nephropathy n 9 light chain deposit disease n 3 mgus group mainly iga nephropathy igan n 10 idiopathic membranous nephropathy n 5 renal monoig group cases igan n 19 chemotherapy mainly administered patients mm group immunosuppression therapy mostly administered patients renal monoig group patients renal monoig exhibited major response followed patients mgus mgrs patients mm partial response none major response approximately half 571 patients mm progressed endstage renal disease esrd followed mgrs 333 however mortality rate low mgrs mm groups survival analysis reviewed serum creatinine hemoglobin levels serum ratio independent risk factors esrd patients mgrsconclusionsthe clinicopathological changes patients mgrs patients mm mgus treatment mgrs mm intensive overall mortality rate low mgus renal monoig alone exhibited slighter clinicopathological features mgrs mm treatment focused mostly primary renal diseases,0.0
neurozika de las ciencias bsicas la prctica clnica revisin de la literatura summaryzika virus zv member flaviviridae family part spondweni serocomplex mainly transmitted aedes vector family first case report unknown exanthematous disease identified brazil subsequently recognized zv infection december 2014 may 2015 zv spread throughout brazil november 2015 association microcephaly congenital abnormalities pregnancy confirmed subsequently multiple neurological alterations reported among pediatric population microcephaly corticospinal alterations neuromuscular symptoms dyskinesia chorioretinal atrophy macular coloboma nystagmus congenital glaucoma sensorineural hearing loss cortical dysplasia ventriculomegaly calcifications hypoplasia brain stem cerebellum afection vermis white matter alteration dysgenesis corpus callosum hydrocephalus dandy walker malformation thinning thoracic portion spinal cord may explain clinical signs congenital zv syndrome also guillainbarre syndrome documented adults incidence 2 3 cases per 10 000 infections less frecuently myelitis encephalitis reported additionally behaviour impairments described well decreased level consciousness seizures meningism finally least frequent manifestations reported far acute disseminated encephalomyelitis peripheral facial palsy myeloradiculopathykeywords zika virus infection zika virus microcephaly guillainbarre syndrome hearing loss mesh,0.0
neurodengue summarydengue virus infection extremely common worldwide countries like colombia high incidence rates dengue although neurological involvement common various forms manifestations described level nervous system central peripheral begun constitute clearly recognized nosological forms encephalitis acute disseminated encephalomyelitis cerebrovascular disease reason clinician essential know conditions require specific prompt therapeutic interventionskeywords dengue central nervous system encephalitis mesh,0.0
comprehensive analysis diabetic nephropathy expression profile based weighted gene coexpression network analysis algorithm background diabetic nephropathy dn major complication diabetes mellitus leading cause endstage renal disease underlying molecular mechanism dn yet completely clear aim study analyze dn microarray dataset using weighted gene coexpression network analysis wgcna algorithm better understanding dn pathogenesis exploring key genes disease progressionmethodsthe identified differentially expressed genes degs dn dataset gse47183 introduced wgcna algorithm construct coexpression modules string database used construction proteinprotein interaction ppi networks genes modules hub genes identified considering degree centrality ppi networks ranked lists weighted networks gene ontology reactome pathway enrichment analyses performed module understand involvement biological processes pathways following validation hub genes another dn dataset gse96804 upstream regulators including micrornas transcription factors predicted regulatory network comprising molecules constructedresultsafter normalization analysis dataset 2475 significant degs identified clustered six different coexpression modules wgcna algorithm degs module subjected functional enrichment analyses ppi network constructions metabolic processes cell cycle control apoptosis among top enriched terms next step 23 hub genes identified among modules genes five including fn1 slc2a2 fabp1 ehhadh pipox validated another dn dataset regulatory network fn1 affected hub gene mir27a real recognized two main upstreamregulators hub genesconclusionsthe identified hub genes hearts coexpression modules widen understanding dn development might targets future investigations exploring therapeutic potentials treatment complicated disease,0.0
inducing sterile pyramidal neuronal death mice model distinct aspects gray matter encephalitis abstractup one person population 10 000 diagnosed lifetime encephalitis 5070 unknown origin recognized causes amount 2050 viral infections approximately one third affected subjects develops moderate severe subsequent damage several neurotropic viruses can directly infect pyramidal neurons induce neuronal death cortex hippocampus resulting encephalitic syndromes frequently associated cognitive deterioration dementia involve numerous parallel downstream cellular molecular events make interpretation direct consequences sudden pyramidal neuronal loss difficult however pivotal understanding neuroinflammatory processes initiate development neurodegeneration thus targeted prophylactic therapeutic interventions utilized adult male nexcreert2xrosa26egfpdta dta mice induction sterile encephalitis diphtheria toxinmediated ablation cortical hippocampal pyramidal neurons also recruits immune cells gray matter report multifaceted aftereffects defined process including expected pathology classical hippocampal behaviors evaluated morris water maze also pre frontal circuit function assessed prepulse inhibition importantly modelled encephalitis mice novel translationally relevant sequelae namely altered social interaction cognition accompanied compromised thermoreaction social stimuli convenient readout parallel autonomic nervous system dys function high resolution magnetic resonance imaging disclosed distinct abnormalities brain dimensions including cortical hippocampal layering well cerebral blood flow volume fluorescent tracer injection immunohistochemistry brain flow cytometry revealed persistent bloodbrainbarrier perturbance chronic brain inflammation surprisingly blood flow cytometry showed abnormalities circulating major immune cell subsets plasma highmobility group box 1 hmgb1 proinflammatory marker remained unchanged present experimental work analyzing multidimensional outcomes direct pyramidal neuronal loss will open new avenues urgently needed encephalitis research,0.0
delaying inevitable disease modifying drugs progressive ms worthwhile abstractocrelizumab siponimod scientifically proven effect progressive ms decrease risk disability shortterm primary endpoints pivotal trials ocrelizumab siponimod reported hazard ratio 3month confirmed disability progression reported 076079 based drugs subsequently licensed use patients progressive multiple sclerosis hazard ratios easily communicated patients therefore alternative endpoint average postponement disability calculated data pivotal trials two years treatment average postponement disability 16 days per year ocrelizumab 19 days siponimod time average postponement disability reached plateau treatment added little value taken together data suggest interventions shortlived limited clinical effect patients progressive ms,0.0
circulating levels tight junction proteins multiple sclerosis association inflammation disease activity disease modifying therapy abstractbackgroundtight junction proteins contribute maintenance epithelial endothelial barriers intestinal barrier blood brain barrier bbb increased permeability barriers linked disease activity ms currently lack easily accessible biomarkers predicting disease activity msaimto investigate whether levels circulating tight junction proteins occludin zonula occludens1 zo1 associated biomarkers inflammation disease activity determine whether serve clinical biomarkersmethodswe prospectively included 72 newly diagnosed patients relapsing remitting ms clinically isolated syndrome prior disease modifying therapy dmt use 50 healthy controls hcs patients followed blood samples 3tesla mri clinical evaluation 12 months occludin zo1 calprotectin soluble urokinasetype plasminogen activator receptor supar measured elisa serum neurofilament light nfl il6 singlemolecule array simoa mrna expression ifng il1r1 il10 il1b arg1 tnf measured quantitative real time polymerase chain reaction qpcr whole bloodresultsplasma occludin levels higher ms patients compared hcs 12 months dmt occludin levels reduced approximately 25 irrespective 1st 2nd line dmt p0001 furthermore nfl calprotectin levels significantly reduced 31 29 respectively occludin zo1 correlate biomarkers inflammation predict disease activity baseline 12 monthsconclusionshigher levels occludin suggest increased permeability bbb intestinal barrier ms patients reduction occludin 12 months dmts might reflect repair barriers upon treatment however plasma levels zo1 occludin predict clinical mri disease activity determined regression roccurve analysis results indicate clear clinically relevant role circulating tight junction proteins biomarkers disease activity ms investigations larger cohorts needed clarify issue,1.0
innovative trial approaches immunemediated inflammatory diseases current use future potential background despite progress made treatment many immunemediated inflammatory diseases imids remains need improved treatments randomised controlled trials rcts provide highest form evidence effectiveness potential new treatment regimen extremely expensive time consuming conduct consequently much focus given recent years innovative design analysis methods improve efficiency rcts article review current use future potential methods within context imid trialsmethodswe provide review several innovative methods provide utility imid research include novel study designs adaptive trials sequential multiassignment randomised trials basket umbrella trials data analysis methodologies augmented analyses composite responder endpoints using highdimensional biomarker information stratify patients emulation rcts routinely collected data imid trials now wellplaced embrace innovative methods example welldeveloped statistical frameworks adaptive trial design ready implementation whilst growing availability historical datasets makes use bayesian methods particularly applicableto assess whether innovative methods used practice conducted review via pubmed clinical trials pertaining 51 imids published 2018 20 five high impact factor clinical journalsresultsamongst 97 articles included review 19 196 used innovative design method relatively straightforward examples innovative approaches two 21 reported use evidence routinely collected data cohorts biobanks eight 92 collected highdimensional dataconclusionsapplication innovative statistical methodology imid trials potential greatly improve efficiency generalise extrapolate trial results personalise treatment strategies currently methods infrequently utilised practice new research required ensure imid trials can benefit suitable methods,1.0
mscsderived exosomes attenuate ischemiareperfusion brain injury inhibit microglia apoptosis might via exosomal mir26a5p mediated suppression cdk6 background study aimed explore role mesenchymal stromal cells mscs derived exosomes mscsexo cerebral ischemiareperfusion r injurymethodsexosomes isolated mscs adult c57bl 6j mice gradient centrifugation method expression mir26a5p cdk6 mscsexo mice brain tissues evaluated qrtpcr western blot mir26a5p mimics mirnc transfected mscs exosomes isolated mscs stably expressing mir26a5p mscsexomir26a5p mimics mscsexomirnc injected mice tail vein added medium stimulate bv2 cells cell viability evaluated cck8 assay cell apoptosis detected flow cytometry apoptosis brain tissues evaluated tunel staining assay bioinformatics analysis luciferase reporter assay performed determine binding relationship mir26a5p cdk6resultsmir26a5p downregulated cdk6 upregulated mscsexo mcaomice ogdinduced mscs mscsexomir26a5p mimics significantly reduced cell apoptosis ogdinjured bv2 cells mscsexomir26a5p mimics significantly reduced infarct volume mcaoinduced mice luciferase reporter assay revealed cdk6 target mir26a5p addition mscsexomir26a5p mimics significantly decreased expression cdk6 ogdinduced bv2 cells brain tissues mcaotreated miceconclusionour results indicated mscsexo attenuated r injury mice inhibiting microglia apoptosis might via exosomal mir26a5p mediated suppression cdk6 study shed light application mscexo potential therapeutic tool cerebral r injury,0.0
vascular endothelial dysfunction associated severity multiple sclerosis endothelial dysfunction multiple sclerosis abstractbackgroundimpairment cerebrovascular reactivity cvr reported patients multiple sclerosis ms chronic inflammation endothelial dysfunction possible mechanisms underlying hemodynamic impairment study aimed evaluate cvr endothelial function patients ms explore relationships disease progression using functional sonographic proceduresmethodspatients ms age sexmatched healthy controls assessed endothelial function determined flowmediated dilation fmd cvr measured using breathholding index bhi resultstwentyseven patients ms 24 healthy controls enrolled fmd significantly lower ms subjects control subjects 60 06 vs 86 07 p 0006 furthermore bhi similarly lower ms controls insignificant remarkably fmd significantly lower secondary progressive ms subjects relapseremitting ms subjects 37 13 vs 67 07 p0045 addition fmd inversely correlated disability score per expanded disability status scale r20170 p0033 modified rankin scale r20187 p0027 conclusionin patients ms endothelial dysfunction noticeable cvr impairment correlating severity progression ms,0.0
hypertension hypertension severity hispanics latinx ms abstractbackgroundvascular comorbidities vcs including hypertension htn associated worse multiple sclerosis ms outcomes htn common latinx prevalence relationship disability unknown latinx msmethodslatinx n451 alliance research hispanic ms arhms seen 2007 2019 included htn diabetes dm hyperlipidemia hld ischemic events smoking considered vc blood pressures bps classified using american heart association aha criteria logistic regression determined associations vc ambulatory disability accounting age sex disease durationresultsmedical comorbidities found 419 vc 242 smoking 136 htn 73 common htn common age 40 126 odds severe disability three times higher htn odds ratio 312 95 confidence interval ci 137712 stage ii htn according aha also tripled odds 289 95ci 111755 aha bp confirmed htn 275 compared 73 established diagnosis conclusionhtn diagnosis stage ii htn defined aha independently associated severe ambulatory disability latinx ms htn underdiagnosed future studies assess whether htn treatment control prevent disability ms,0.0
psychometric properties modified mos social support survey 5item msss5item among iranian older adults background social support key factor public health since precise evaluation critical current study developed evaluate psychometric properties mossss questionnaires abbreviated form msss5item among iranian older adultsmethodsthis crosssectional methodological study conducted 420 community older adults age 60 random multistage sampling questionnaire first translated persian forward backward method based guidelines next validity scales investigated calculating face validity content validity knowngroup validity explanatory factor analysis confirmatory factor analysis indices reliability questionnaire calculated internal consistency testretest absolute reliability moreover scalability questionnaire checked mokken scale analysis software packages spss version 22 amos version 22 r mokken package employed analyze dataresultsthe face validity conducted using interviews older adults gathering specialists opinions items grammatically lexically corrected accordingly cvi index overall scale 094 every single item 089 results independent ttest showed current questionnaire well distinguished older adults feel lonely p 0001 two components recognized according explanatory factor analysis together explained 6778 total variance questionnaire cfa showed twofactor model acceptable fit indices questionnaire desirable internal consistency 078 stability icc 098 absolute reliability sem 056 mdc 157 furthermore mokken scale proved msss5item strong scale h 051 se 003 conclusionthe present study results showed msss5item questionnaire suitable validity reliability used among iranian older adults,0.0
ethical considerations treatment multiple sclerosis fatigue abstractfatigue common symptom leading cause disability multiple sclerosis ms despite lack evidence several medications frequently prescribed physicians ameliorate fatigue patients ms however recent study demonstrated improvement fatigue severity medications appears due placebo effect also associated frequent adverse events placebo findings raise ethical concerns surrounding initiation discontinuation treatments fatigue ms starting medications treatment ms fatigue placebo effect may justified however stopping medications patients report symptomatic benefits side effects may also ethical ms care nonpharmacological approaches fatigue treatment exercise cognitive behavioral therapy now prioritized novel study designs may necessary address placebo response future clinical trials evaluating interventions fatigue ms,0.0
mammalian mechanistic target rapamycin mtor complexes neurodegeneration abstractnovel targets arrest neurodegeneration several dementing conditions involving misfolded protein accumulations may found diverse signaling pathways mammalian mechanistic target rapamycin mtor nutrient sensor mtor important homeostatic functions regulate energy metabolism support neuronal growth plasticity however alzheimers disease ad mtor alternately plays important pathogenic roles inhibiting insulin signaling autophagic removal amyloid phosphotau ptau aggregates also plays role cerebrovascular dysfunction ad mtor serine threonine kinase residing core either two multiprotein complexes termed mtorc1 mtorc2 recent data suggest balanced actions also implications parkinsons disease pd huntingtons disease hd frontotemporal dementia ftd amyotrophic lateral sclerosis als beyond rapamycin mtor inhibitor rapalogs greater tolerability micro delivery modes hold promise arresting age dependent conditions,0.0
significance oxidative stress markers oneyear prognosis patients acute ischemic stroke casecontrol study background stroke major cause mortality morbidity also free radicals oxidative stress deleterious factor stroke progression aimed evaluate association oxidative stress markers odds risk factor stroke developing strokemethodsthe present casecontrol study conducted 556 participants imamreza hospital tabriz iran subjects divided three group including individuals acute ischemic stroke risk stroke healthy controls enrolled participants except controls underwent neurological examinations brain magnetic resonance imaging mri strokerelated disability stroke severity evaluated modified rankin scale mrs national institutes health stroke scale nihss respectively serum malondialdehyde mda level total antioxidant capacity tac measured within 48 h initiation stroke oneway anova chisquare tests used comparing characteristics groups multivariable logistic regression implemented odds stroke based mda tac quartiles also spearmans correlation utilizedresultsserum mda systolic diastolic blood pressure cholesterol triglyceride significantly higher stroke group controls high levels mda associated increased development stroke pvalue 0001 however tac mda associated risk factors stroke pvalue 100 027 respectively also tac level negatively associated baseline 028 pvalue 004 followup 031 pvalue 003 nihss scores moreover mda correlated mrs score followup 026 pvalue 004 conclusionsthe balance antioxidants oxidants markers might reveal new approach context studies warranted identify source oxidative stress well cessation production oxygen radicals stroke,0.0
effects venlafaxine risperidone febuxostat cuprizoneinduced demyelination behavioral deficits oxidative stress int j mol sci 2021 jul 2 22 13 7183 doi 103390 ijms22137183abstractmultiple sclerosis ms demyelinating autoimmune disease affects large number young adults novel therapies ms needed considering efficiency safety limitations current treatments study investigated effects venlafaxine antidepressant serotoninnorepinephrine reuptake inhibitor risperidone atypical antipsychotic febuxostat gout medication xanthine oxidase inhibitor cuprizone mouse model acute demyelination hypothesizing antagonistic effect trpa1 calcium channels cuprizone drugs administered c57bl6 j mice five weeks locomotor activity motor performance cold sensitivity assessed mice brains harvested histological staining assessment oxidative stress markers febuxostat metabolites venlafaxine desvenlafaxine risperidone paliperidone tested trpa1 antagonistic activity following treatment venlafaxine risperidone significantly improved motor performance sensitivity cold stimulus administered drugs ameliorated cuprizoneinduced deficit superoxide dismutase activity desvenlafaxine paliperidone showed activity trpa1 febuxostat exhibited agonistic activity high concentrations findings indicated three drugs offered protection effects cuprizoneinduced demyelination agonistic activity febuxostat can potential use discovering novel trpa1 ligandspmid34281235 doi103390 ijms22137183,1.0
psychometric evaluation perceived access health care questionnaire background objectiveaccess health care universal concern therefore study conducted develop questionnaire assess perceived access health care based penchansky thomass definition access assessment psychometric propertiesmethodthe initial questionnaire contains 31 items developed based deductive approach extensive review related literature content validity face validity construct validity internal consistency instrument reliability examined data analysis conducted using spss software version 24 r software version 4 lavaan packageresultsthe initial questionnaire examined using qualitative content validity necessary modifications applied item content validity ratio cvr approved 30 items value greater 078 one item cvr value lower 078 removed case content validity index cvi 29 items approved cvi value greater 079 one item cvi value 070 079 revised qualitative face validity items approved panel experts participants 30 items impact score index higher 15 approved next steps confirmatory factor analysis results showed sixfactor model access health care appropriate fit cronbachs alpha coefficient questionnaire calculated 086 value cronbachs alpha dimensions availability accessibility affordability accommodation acceptability awareness 061 076 066 060 080 076 respectively intraclass correlation index icc value reliability testretest whole instrument calculated 094 using twoway mixed absolute agreement methodconclusionthe success health programs depends eliminating barriers access provided health care services one critical barriers understanding access perception limited access questionnaire might used understand perceived health care access different global contexts,0.0
influence highimpact multidimensional rehabilitation program gut microbiota patients multiple sclerosis int j mol sci 2021 jul 2 22 13 7173 doi 103390 ijms22137173abstractmultiple sclerosis ms neurodegenerative inflammatory condition mediated autoreactive immune processes due potential influence host immunity gutbrain communication gut microbiota suggested involved onset progression ms date definitive cure ms rehabilitation programs utmost importance especially later stages however people generally participate due poor support knowledge motivation information available gut microbiota changes herein evaluated potential brief highimpact multidimensional rehabilitation program bhipe leisure environment affect gut microbiota mitigate ms symptoms improve quality life bhipe resulted modulation mstypical dysbiosis reduced levels pathobionts replenishment beneficial shortchain fatty acid producers partial recovery eubiotic profile help counteract inflammatory tone typically observed ms supported reduced circulating lipopolysaccharide levels decreased populations proinflammatory lymphocytes improved physical performance fatigue relief also found findings pave way integrating clinical practice holistic approaches mitigate ms symptoms improve patients quality lifepmid34281224 doi103390 ijms22137173,0.0
imaging biomarkers evaluating tumor response recist beyond abstractresponse evaluation criteria solid tumors recist gold standard assessment treatment response solid tumors morphologic change tumor size evaluated recist often correlated survival length considered surrogate endpoint therapeutic efficacy however detection morphologic change alone may sufficient assessing response new anticancer medication solid tumors past fifteen years several moleculartargeted therapies immunotherapies emerged cancer treatment work disrupting signaling pathways inhibited cell growth tumor necrosis lack tumor progression associated good therapeutic response even absence tumor shrinkage therefore use unmodified recist criteria estimate morphological changes tumor alone may sufficient estimate tumor response new anticancer drugs several studies reported low reliability recist evaluating treatment response different tumors hepatocellular carcinoma lung cancer prostate cancer brain glioma bone metastasis lymphoma increased need new medical imaging biomarkers considering changes tumor viability metabolic activity attenuation related early tumor response promising imaging techniques beyond recist include dynamic contrastenhanced computed tomography ct magnetic resonance imaging mri diffusionweight imaging dwi magnetic resonance spectroscopy mrs 18 ffluorodeoxyglucose fdg positron emission tomography pet review outlines current recist limitations new emerging concepts imaging biomarkers oncology,0.0
discontinuation diseasemodifying therapy multiple sclerosis stay go jama neurol 2021 apr 19 doi 101001 jamaneurol20210764 online ahead printno abstractpmid33871561 doi101001 jamaneurol20210764,0.0
selling cannabidiol products canada framing analysis advertising claims online retailers background canada legalization cannabis enabled cannabidiol cbd become popular commercial product increasingly used medical therapeutic purposes currently one thousand cbd products available globally ranging oil extracts cbdinfused beverages despite increased usage availability evidence supporting medical efficacy cbd limited anecdotal evidence suggests cbd sellers represent products medical use direct medical claims advice canada allowed cannabis act without health canada approval however clear extent sellers making health claims strategies used promote medical usage cbd objective study determine cbd sellers advertise products online consumersmethodsthe product descriptions 2165 cbd products 70 websites selling cbd products human consumption canada collected january 14th 2020 february 2nd 2020 using automated website scraper tool framing analysis used determine cbd sellers frame products prospective customers specific medical conditions cbd represented treat product forms tabulatedresultscbd products framed prospective customer three distinct frames specific cure treatment n 1153 natural health product n 872 product used certain ways achieve particular results n 1388 product descriptions contained medical therapeutic claims 171 medical conditions ailments 533 products containing least one claim prevalent claims found product descriptions ability treat manage pain n 824 anxiety n 609 inflammation n 545 claims found treating managing serious andlifethreatening illnesses multiple sclerosis n 210 arthritis n 179 cancer n 169 crohns disease n 78 parkinsons disease n 59 human immunodeficiency virus hiv n 54 cbd often came oil tincture concentrate form n 755 followed edibles n 428 vaporizer pen cartridge liquid products n 290 conclusionthe findings suggest cbd represented medical option numerous conditions ailments recommend health canada conduct systematic audit companies selling cbd regulatory adherence,0.0
targeting gut treat multiple sclerosis j clin invest 2021 jul 1 131 13 143774 doi 101172 jci143774abstractthe gutbrain axis gba refers complex interactions gut microbiota nervous immune endocrine systems together linking brain gut functions perturbations gba reported people multiple sclerosis pwms suggesting possible role disease pathogenesis making potential therapeutic target research area still infancy number studies revealed pwms likely exhibit altered microbiota altered levels short chain fatty acids secondary bile products increased intestinal permeability however specific microbes metabolites identified across studies cohorts vary greatly small clinical preclinical trials pwms mouse models microbial composition manipulated use antibiotics fecal microbiota transplantation probiotic supplements provided promising outcomes preventing cns inflammation however results always consistent largescale randomized controlled trials lacking herein give overview gba contribute ms pathogenesis examine different approaches tested modulate gba discuss may impact neuroinflammation demyelination cnspmid34196310 doi101172 jci143774,1.0
multiple sclerosis spotlight multiple sclerosis affects estimated 28 million people worldwide although past years seen substantial improvements procedures diagnosis prognosis monitoring expansion therapeutic landscape stark disparities care people disease third edition multiple sclerosis international federation msif atlas ms reports twothirds patients multiple sclerosis worldwide living countries national guidelines diagnosis treatment disease world brain day july 22 engagement msif joining forces world federation neurology advocate heightened focus improving quality life people multiple sclerosis care partners atlas ms launched 2008 msif collaboration address absence data multiple sclerosis many countries part 1 third edition atlas reports prevalence incidence multiple sclerosis 115 countries part 2 atlas drawing data 107 countries highlights many barriers inequalities patients can face get diagnosis also access disease modifying therapies dmts rehabilitation early diagnosis multiple sclerosis essential either enable prompt treatment dmts can minimise relapses reduce future disability therapies available allow lifestyle changes help manage disease improve quality life according msif atlas implementation 2017 mcdonald diagnostic criteria clinical practice correlates country wealth around 98 highincome countries compared less half 40 lowincome countries using criteria common barrier use lack awareness training neurologists worryingly 83 countries barriers preclude early diagnosis multiple sclerosis scarcity qualified healthcare professionals prohibitive cost diagnostic equipment tests msif atlas also uncovers fundamental barriers equitable access treatment experts 14 countries surveyed report licensed dmts available proportion increases 70 lowincome countries including 60 african countries globally common barrier accessing therapies high cost challenges low number healthcare professionals poor knowledge dmts among clinicians logistical problems continuous supply dmts msif atlas also reports high unmet need rehabilitation symptom management particularly lowincome countries essential good quality life therapies fatigue cognitive impairment available twofifths countries new evidencebased recommendations use mri diagnosis prognosis disease monitoring multiple sclerosis unify guidelines european north american expert groups recommendations address major issues concerning use mri clinical practice arisen past years highlight essential role mri diagnosis well assessment treatment efficacy prediction treatment response however recommendations unlikely widely applicable lowincome countries regular use imaging procedures challenging msif atlas makes recommendations address disparities care including calls every country national plan dedicated management guidelines improvements availability affordability range dmts advocacy efforts evidencebased guidance use offlabel dmts joint efforts organisations networks focus neurological conditions tackle shared challenges number training neurologists access costeffective approaches management stronger collaboration healthcare authorities research institutions patient organisations healthcare professionals collection data establish monitor care standards development new potentially sensitive specific imaging techniques currently widely available represents important opportunity new treatments emerge however addressing imbalances care essential ensure people affected multiple sclerosis able benefit progress field,0.0
corrigendum optical coherence tomography neuromyelitis optica spectrum disorder multiple sclerosis populationbased study multiple sclerosis related disorders volume 47 2021 18 102625 corrigendum optical coherence tomography neuromyelitis optica spectrum disorder multiple sclerosis populationbased study multiple sclerosis related disorders volume 47 2021 18 102625,0.0
autoimmune brainstem encephalitis illustrative case review literature j clin med 2021 jul 1 10 13 2970 doi 103390 jcm10132970abstractautoimmune brainstem encephalitis bse rare neurological condition wide range underlying etiologies can subdivided two broad groups primary inflammatory disease central nervous system cns brainstem disorder secondary systemic diseases cns one many affected organs symptoms range mild lifethreatening manifestations cases respond well immunotherapy therefore broad indepth knowledge various inflammatory disorders target brainstem essential guiding diagnostic approach assisting early initiation appropriate therapy herein report case bse provide overview various causes autoimmune bse emphasis clinical manifestations diagnostic approachpmid34279454 doi103390 jcm10132970,0.0
calcitonin generelated peptide cgrp receptor antagonists heterocyclic modification novel azepinone lead bioorg med chem lett 2021 apr 28128077 doi 101016 jbmcl2021128077 online ahead printabstractin efforts identify orally bioavailable cgrp receptor antagonists previously discovered novel series orally available azepinone derivatives unfortunately also exhibited unwanted property potent timedependent human cyp3a4 inhibition heterocyclic replacement indazole ring discovered series heterocycle derivatives highaffinity cgrp receptor antagonists showed reasonable oral exposures imidazolone derivatives showed good oral exposure also exhibited substantially reduced timedependent cyp3a4 inhibition several compounds showed strong vivo efficacy marmoset facial blood flow assay 87 inhibition cgrpinduced activity however oral bioavailability generally remained low emphasizing challenges others encountered discovering clinical development candidates difficult class b gpcr targetpmid33932522 doi101016 jbmcl2021128077,0.0
navigatorguided motion b0 correction t2weighted magnetic resonance imaging improves multiple sclerosis cortical lesion detection invest radiol 2021 jul 1 56 7 409416 doi 101097 rli0000000000000754abstractbackground cortical lesions common multiple sclerosis ms t2weighted t2w imaging 7 t relatively sensitive cortical lesions quality often compromised motion main magnetic field b0 fluctuationspurpose aim study determine whether motion b0 correction navigatorguided gradientrecalled echo sequence can improve cortical lesion detection t2w magnetic resonance imagingmaterials methods prospective study gradientrecalled echo sequence incorporating navigator allowing motion b0 field correction applied collect t2w images 7 t adults ms august 2019 march 2020 t2weighted images acquired 1 3 partially overlapping scans per individual reconstructed using global average b0 correction uncorrected motion correction spatially linear b0 correction corrected image quality rating manual segmentation cortical lesions performed uncorrected corrected images lesions seen single scan retrospectively evaluated complementary scan association cortical lesions clinical disability assessed mixed models used determine effect correction lesion detection well relationship disability lesion countresults total 22 t2w scans performed 11 adults ms mean sd age 49 11 years 8 women quality improved 20 22 scans 91 correction total 69 cortical lesions identified uncorrected images median per scan 2 range 011 versus 148 corrected images median per scan 45 range 025 rate ratio rr 21 p 00001 lowquality uncorrected scans moderate severe motion artifact 18 22 82 improvement cortical lesion detection correction rr 25 p 00001 whereas significant change cortical lesion detection highquality scans rr 13 p 043 conclusions navigatorguided motion b0 correction substantially improves overall image quality t2w magnetic resonance imaging 7 t increases sensitivity cortical lesionspmid34086012 doi101097 rli0000000000000754,0.0
burden transportrelated injuries eastern mediterranean region systematic analysis global burden disease study 2017 arch iran med 2021 jul 1 24 7 512525 doi 1034172 aim202174abstractbackground transportrelated injuries tis substantial public health concern regions world present study quantified burden tis deaths eastern mediterranean region emr 2017 sex agemethods tis deaths estimated age sex country year using cause death ensemble modelling codem dismodmr 21 disabilityadjusted life years dalys quantify total burden years lost due premature death disability also estimated per 100000 population estimates reported along corresponding 95 uncertainty intervals uis results 2017 55 million ui 4962 transportrelated incident cases emr substantial increase 1990 28 million ui 2531 agestandardized incidence rate emr 2017 787 ui 70558762 per 100000 changed significantly since 1990 09 ui 47 3 rates differed remarkably countries oman 13039 ui 1167314415 palestine 4865 ui 43455459 highest lowest agestandardized incidence rates per 100000 respectively 2017 1853 thousand ui 17082006 transportrelated fatalities emr substantial increase since 1990 1404 thousand ui 11871569 agestandardized death rate emr 2017 295 ui 271319 per 100000 305 lower found 1990 425 ui 368473 2017 somalia 54 ui 30774 lebanon 71 ui 4886 highest lowest agestandardized death rates per 100 000 respectively agestandardised daly rate emr 2017 1 5288 ui 1412516513 per 100000 344 lower found 1990 2 3313 ui 1 99312 5899 2017 highest daly rate found pakistan 3454121 ui 2297890 4342908 lowest found bahrain 8616 ui 76709751 conclusion present study shows road traffic become relatively safer measured deaths dalys per 100000 population number transportrelated fatalities emr growing needs addressed urgentlypmid34488316 doi1034172 aim202174,0.0
modulation striatal functional connectivity differences adults without autism spectrum disorder singledose randomized trial cannabidivarin background autism spectrum disorder asd high cost affected individuals society treatments core symptoms lacking expand intervention options crucial gain better understanding potential treatment targets engagement brain instance striatum caudate putamen nucleus accumbens plays central role development atypical functional connectivity fc may contribute multiple asd symptoms previously shown adult autistic neurotypical brain nonintoxicating cannabinoid cannabidivarin cbdv alters balance striatal excitatoryinhibitory metabolites help regulate fc effects cbdv atypical striatal fc unknownmethodsto examine small pilot study acquired resting state functional magnetic resonance imaging data 28 men 15 neurotypicals 13 asd two occasions repeatedmeasures doubleblind placebocontrolled study used seedbased approach 1 compare striatal fc groups 2 examine effect pharmacological probing 600 mg cbdv matched placebo atypical striatal fc asd visits separated least 13 days allow drug washoutresultscompared neurotypicals asd individuals lower fc ventral striatum frontal pericentral regions associated emotion motor vision processing higher intrastriatal fc higher putamenal fc temporal regions involved speech language asd cbdv reduced hyperconnectivity neurotypical levellimitationsour findings considered light several methodological aspects particular participant group restricted male adults limits generalizability findings wider heterogeneous asd populationconclusionin conclusion show atypical striatal fc regions commonly associated asd symptoms provide preliminary proof concept adult autistic brain acute cbdv administration can modulate atypical striatal circuitry towards neurotypical function future studies required determine whether modulation striatal fc associated change asd symptomstrial registrationclinicaltrialsgov identifier nct03537950 registered may 25th 2018retrospectively registered https clinicaltrialsgov ct2 show nct03537950termnct03537950draw2rank1,0.0
targeting mitochondrialderived reactive oxygen species t cellmediated autoimmune diseases front immunol 2021 jul 1 12703972 doi 103389 fimmu2021703972 ecollection 2021abstractmitochondrial dysfunction resulting oxidative stress associated tissue cell damage common many t cellmediated autoimmune diseases autoreactive cd4 t cell effector subsets th1 th17 driving diseases require increased glycolytic metabolism upregulate key transcription factors tf like tbet rort drive differentiation proinflammatory responses however research immunometabolism demonstrated mitochondrialderived reactive oxygen species ros act signaling molecules contributing t cell fate function eliminating autoreactive t cells targeting glycolysis ros production potential strategy inhibit autoreactive t cell activation without compromising systemic immune function additionally increasing selftolerance promoting functional immunosuppressive cd4 t regulatory treg cells another alternative therapeutic autoimmune disease tregs require increased ros oxidative phosphorylation oxphos foxp3 tf expression differentiation antiinflammatory il10 cytokine synthesis decreasing glycolytic activity increasing glutathione superoxide dismutase antioxidant activity can also beneficial inhibiting cytotoxic cd8 t cell effector responses current treatment options t cellmediated autoimmune diseases type 1 diabetes t1d multiple sclerosis ms rheumatoid arthritis ra systemic lupus erythematosus sle include global immunosuppression antibodies deplete immune cells anticytokine therapy effective diminishing autoreactive t cells can also compromise immune responses resulting increased susceptibility diseases complications impact mitochondrialderived ros immunometabolism reprogramming autoreactive t cell differentiation potential target t cellmediated autoimmune diseases exploiting pathways may delay autoimmune responses t1dpmid34276700 pmcpmc8281042 doi103389 fimmu2021703972,0.0
origins potency heterogeneity skeletal muscle fibroadipogenic progenitorstime new definitions abstractstriated muscle highly plastic regenerative organ regulates body movement temperature metabolismall functions needed individuals health wellbeing muscle connective tissues main components extracellular matrix resident stromal cells continuously reshape embryonic development homeostasis regeneration fibroadipogenic progenitors enigmatic transformative muscleresident interstitial cells mesenchymal stem stromal cell properties act cellular sentinels physiological hubs adult muscle homeostasis regeneration shaping microenvironment secreting complex cocktail extracellular matrix components diffusible cytokines ligands immunemodulatory factors fibroadipogenic progenitors lineage precursors specialized cells including activated fibroblasts adipocytes osteogenic cells injury discuss current research gaps potential druggable developments outstanding questions fibroadipogenic progenitor origins potency heterogeneity finally took advantage recent advances singlecell technologies combined lineage tracing unify diversity stromal fibroadipogenic progenitors thus compelling review provides new cellular molecular insights comprehending origins definitions markers fate plasticity murine human fibroadipogenic progenitors muscle development homeostasis regeneration repair,0.0
case report pansynostosis chiari malformation syringomyelia child frontometaphyseal dysplasia 1 front pediatr 2021 jul 1 9574402 doi 103389 fped2021574402 ecollection 2021abstractfrontometaphyseal dysplasia 1 fmd1 rare otopalatodigital spectrum disorder opdsd inherited xlinked trait caused gainoffunction mutations flna characterized generalized skeletal dysplasia craniofacial abnormalities including facial dysmorphism supraorbital hyperostosis hypertelorism downslanting palpebral fissures involvement central nervous system patients opdsd rare herein present case 12yearold boy facial dysmorphism multiple joint contractures sensorineural hearing loss scoliosis craniosynostosis irregular sclerosis hyperostosis skull brain wholespine magnetic resonance imaging revealed chiari malformation extensive hydrosyringomyelia c1 t12 levels targeted nextgeneration sequencing identified hemizygous pathologic variant c3557ct pser1186leu flna confirming diagnosis fmd1 first report rare case opdsd pansynostosis chiari malformation accompanied extensive syringomyeliapmid34277511 pmcpmc8280522 doi103389 fped2021574402,0.0
effects natalizumab therapy intrathecal immunoglobulin g production indicate targeting plasmablasts neurol neuroimmunol neuroinflamm 2021 jul 1 8 5 e1030 doi 101212 nxi0000000000001030 print 2021 julabstractobjectives evaluate longterm effects natalizumab ntz different features intrathecal immunoglobulin ig synthesis patients multiple sclerosis ms quantify expression 4integrin stages bcell maturationmethods combined crosssectional 49 ntztreated ms patients mean treatment duration 51 years 47 untreated ms patients longitudinal study 33 patients ms ntz mean treatment duration 48 years analyzing paired serum csf samples igg iga igm levels reactivity selected viruses measles virus rubella virus varicella zoster virus mrz reaction oligoclonal bands ocbs banding patterns therapy directly compared isoelectric focusing 1 patient addition determined expression 4integrin facs analysis bloodderived bcell subsets plasmablasts memory b cells naive b cells healthy controlsresults serum ntz decreased igm igg iga levels igm hypogammaglobulinemia occurred 28 ntztreated patients csf ntz treatment resulted strong reduction intrathecally produced igg lesser extent iga whereas igm indices ig csf serum albumin csf serum remained largely unchanged reduction igg index correlated ntz treatment duration serum igm iga levels mrz reaction unchanged ocb persisted direct comparison ocb pattern ntz revealed persistence individual bands 4integrin expression highest plasmablasts cd19+cd38+cd27+ conclusion data indicate ntz reduces shortlived plasmablasts cns compartment little effect locally persisting longlived plasma cellspmid34210800 doi101212 nxi0000000000001030,0.0
evidence occupational therapy interventions supporting work social participation adults multiple sclerosis systematic review j occup ther 2021 jul 1 75 4 7504190020 doi 105014 ajot2021048058abstractimportance evidence supports interventions work social participation adults multiple sclerosis ms objective systematically collect evaluate evidence effectiveness interventions within scope occupational therapy practice improve maintain performance participation education work volunteering leisure social participation among adults msdata sources medline psycinfo cinahl otseeker cochrane database systematic reviews searches articles published january 2011 december 2018 study selection data collection two independent reviewers analyzed articles using cochrane methodology articles assessed terms inclusion exclusion criteria quality risk biasfindings although review developed address education work volunteering leisure social participation work social participation outcomes found literature six hundred eighteen articles reviewed 4 articles met inclusion criteria one level 1b study 1 level 3b study provided moderate strength evidence moderate risk bias online work intervention improve selfesteem better understand career goals one level 3b study provided low strength evidence interdisciplinary rehabilitation address work finally 1 level 1b study yoga group intervention provided moderate strength evidence low risk bias improve social participationconclusions relevance review highlights lack evidence related various types participation adults ms evidence focused work social participation limited article adds review highlights need interventions within scope occupational therapy increased participation adults mspmid34780613 doi105014 ajot2021048058,0.0
living edge cns meninges cell diversity health disease front cell neurosci 2021 jul 1 15703944 doi 103389 fncel2021703944 ecollection 2021abstractthe meninges fibrous covering central nervous system cns contain vastly heterogeneous cell types within three layers dura arachnoid pia dural compartment meninges closest skull predominantly composed fibroblasts also includes fenestrated blood vasculature elaborate lymphatic system well immune cells distinct cns segregating outer inner meningeal compartments epitheliallike arachnoid barrier cells connected tight adherens junctions regulate movement pathogens molecules cells cerebral spinal fluid csf brain parenchyma proximate brain collagen basement membranerich pia matter abuts glial limitans recently shown regional heterogeneity within developing mouse brain meninges historically seen purely structural support cns protection trauma emerging view meninges essential interface cns periphery critical brain development required brain homeostasis involved variety diseases review will summarize known regarding development specification maturation meninges homeostatic conditions discuss rapidly emerging evidence specific meningeal cell compartments play differential important roles pathophysiology myriad diseases including multiple sclerosis dementia stroke viral bacterial meningitis traumatic brain injury cancer will conclude list major questions mechanisms remain unknown study represent new future directions field meninges biologypmid34276313 pmcpmc8281977 doi103389 fncel2021703944,0.0
sarscov2 antibodies adult patients multiple sclerosis amsterdam ms cohort jama neurol 2021 apr 30 doi 101001 jamaneurol20211364 online ahead printno abstractpmid33929488 doi101001 jamaneurol20211364,0.0
aseptic neutrophilic meningitis hypoglycorrhachia following single ocrelizumab infusion neurol neuroimmunol neuroinflamm 2021 jul 1 8 5 e1025 doi 101212 nxi0000000000001025 print 2021 sepno abstractpmid34210799 doi101212 nxi0000000000001025,0.0
influence pregnancy multiple sclerosis impact diseasemodifying therapies front neurol 2021 jul 1 12697974 doi 103389 fneur2021697974 ecollection 2021abstractpurpose review article systematic review influence pregnancy multiple sclerosis resulting impact diseasemodifying therapies findings multiple sclerosis predominantly affects young women clinical onset often childbearing age impact multiple sclerosis diseasemodifying therapies fertility pregnancy fetal outcome breastfeeding pivotal topic comes clinical practice introduction diseasemodifying therapies changed natural history disease also perspective pregnancy women multiple sclerosis family planning requires careful consideration especially many diseasemodifying drugs contraindicated pregnancy article review current evidence collected published literature drugspecific pregnancy registers use diseasemodifying therapies additionally discuss safety profiles drug correlate risk exposed fetus risk mothers interrupting treatments seeking pregnancypmid34276545 pmcpmc8280312 doi103389 fneur2021697974,0.0
dual targeting mek pi3k effectively controls proliferation human egfrtki resistant nonsmall cell lung carcinoma cell lines different genetic backgrounds background molecular targeted therapy nonsmall cell lung carcinoma nsclc restricted due resistance epidermal growth factor receptor egfr tyrosine kinase inhibitors tkis study evaluated effects dual targeting mek pi3k human egfrtki resistant nsclc cell linesmethodsegfrtki resistant nsclc cell lines h1975 h460 a549 different mutation amplification status egfr kras pik3ca met genes treated mek162 mek inhibitor bkm120 pi3k inhibitor combination bibw2992 egfr inhibitor arq197 met inhibitor combination assayed cell proliferation apoptosis cell cycle distributionresultsdual targeting mek pi3k efficiently inhibited cell proliferation induced apoptosis g0 g1 cell cycle decreased phosphorylation erk1 2 akt s6 4ebp1 h460 cells kras pik3ca mutation sensitive mek162 bkm120 combinations h1975 cells egfr pik3ca mutation met amplification sensitive bibw2992 arq197 combinationsconclusiondual targeting regulated proliferation egfrtkiresistant nsclc cells especially mutants kras pik3ca promising egfrtkiresistant nsclc therapeutics,0.0
association marker nacetylglucosamine progressive multiple sclerosis neurodegeneration jama neurol 2021 may 10 doi 101001 jamaneurol20211116 online ahead printabstractimportance nglycan branching modulates cell surface receptor availability deficiency mice promotes inflammatory demyelination reduced myelination neurodegeneration nacetylglucosamine glcnac ratelimiting substrate nglycan branching knowledge endogenous serum levels patients multiple sclerosis ms unknownobjective investigate marker endogenous serum glcnac levels patients msdesign setting participants crosssectional discovery study crosssectional confirmatory study conducted 2 academic ms centers us germany discovery study recruited 54 patients ms outpatient clinic well 66 healthy controls april 20 2010 june 21 2013 confirmatory study recruited 180 patients ms screening visits academic ms study center april 9 2007 february 29 2016 serum samples analyzed december 2 2013 march 2 2015 statistical analysis performed february 23 2020 march 18 2021main outcomes measures serum levels glcnac plus stereoisomers termed nacetylhexosamine hexnac assessed using targeted tandem mass spectroscopy secondary outcomes confirmatory study comprised imaging clinical disease markersresults discovery cohort included 66 healthy controls 38 women mean sd age 42 20 years 33 patients relapsingremitting ms rrms 25 women mean sd age 50 11 years 21 patients progressive ms pms 14 women mean sd age 55 7 years confirmatory cohort included 125 patients rrms 83 women mean sd age 40 9 years 55 patients pms 22 women mean sd age 49 80 years discovery cohort mean sd serum level glcnac plus stereoisomers hexnac 710 174 nm healthy controls marginally reduced patients rrms mean sd level 682 173 nm p 04 whereas patients pms displayed markedly reduced levels compared healthy controls mean sd level 548 101 nm p 955 109 patients rrms p 183 104 difference patients rrms mean sd level 709 193 nm pms mean sd level 405 161 nm p 76 1018 confirmed independent confirmatory cohort lower hexnac serum levels correlated worse expanded disability status scale scores 0485 p 473 1012 lower thalamic volume t 17 p 04 thinner retinal nerve fiber layer b 0012 se 75 1011 p 008 low baseline serum hexnac levels correlated greater percentage brain volume loss 18 months t 18 p 04 conclusions relevance study suggests deficiency glcnac plus stereoisomers hexnac may biomarker pms previous preclinical human genetic ex vivo human mechanistic studies revealed nglycan branching glcnac may reduce proinflammatory responses promote myelin repair decrease neurodegeneration combined data suggest glcnac deficiency may associated progressive disease neurodegeneration patients mspmid33970182 doi101001 jamaneurol20211116,1.0
crossed molecular beams computational study formation astronomically elusive thiosilaformyl radical hsis x2a#39 j phys chem lett 2021 jun 2359795986 doi 101021 acsjpclett1c01706 online ahead printabstractthe formation pathways silicon sulfurcontaining molecules crucial understanding siliconsulfur chemistry interstellar circumstellar environments multiple silicon sulfurcontaining species observed deep space fundamental formation mechanisms largely unknown crossed molecular beams technique combined electronic structure riceramspergerkasselmarcus rrkm calculations utilized study bimolecular reaction atomic silicon si 3pj thiomethanol ch3sh x1a leading thiosilaformyl radical hsis x2a via exclusive methyl radical ch3 x2a2 loss via indirect scattering dynamics involves barrierless addition hydrogen migration overall exoergic reaction indicating possibility hsis can form cold molecular clouds astronomically elusive thiosilaformyl radical may act tracer exotic siliconsulfur chemistry deciphered toward example starforming region sgrb2 thus leading better understanding formation siliconsulfur bonds deep spacepmid34161096 doi101021 acsjpclett1c01706,0.0
ruxolitinib attenuates experimental autoimmune encephalomyelitis eae development animal models multiple sclerosis ms life sci 2021 mar 26119395 doi 101016 jlfs2021119395 online ahead printabstractaims stat3 signaling critical th17 development plays important role multiple sclerosis pathogenesis evaluate antiinflammatory regulatory t cells effects jak1 2 stat3 inhibition assessed jak 1 2 inhibitor ruxolitinib effects th17 cell tregs balancemain methods ruxolitinib administered experimental autoimmune encephalomyelitis eae mice via oral gavage effects assessed expression proinflammatory antiinflammatory cytokines including il17a il10 analyzed realtime pcr frequency th17 cells tregs evaluated flow cytometrykey finding ruxolitinib ameliorated eae severity decreased proportion th17 cells inflammatory markers levels contrast balance tregs level antiinflammatory cytokine increased ruxolitinibtreated mice furthermore ruxolitinib markedly decreased expression th17 related transcription factor rort whereas foxp3 expression associated treg differentiation increasedsignificance results show ruxolitinib may promising therapeutic strategy multiple sclerosispmid33781828 doi101016 jlfs2021119395,0.0
womanist approach caring patients empirically unverifiable symptoms ama j ethics 2021 jul 1 23 7 e519523 doi 101001 amajethics2021519abstractsome illnesses diseases apparent onlookers conditions like chronic fatigue syndrome fibromyalgia multiple sclerosis postconcussive syndrome endometriosis many psychiatric illnesses example symptoms easily measurable clinicians health care systems however tend focus exclusively measurability can result evidentiary overreliance undervaluation experience narratives can clinically ethically socially important consequences patients conditionspmid34351260 doi101001 amajethics2021519,0.0
encefalomielitis txica por anestesia espinal presentacin de un caso introductionneurological complications consequence spinal anesthesia frequently reported due extensive use can cause toxic myelopathycase presentationa 26yearsold patient health history admitted freyre de andrade clinical surgical hospital 24 hours surgery hemorrhoids spinal anesthesia hyperbaric lidocaine begins right palpebral ptosis difficulty walking discharged two days later admitted drowsiness stiff neck positive csf suspected meningoencephalitis evolves coma satisfactory response antibiotics 14 days cerebral edema autonomic disorders alternating hemiparesis flaccid paraplegia noted antibiotic withdrawn treated parenteral betamethasone two months plus physiotherapy 10 months progressive improvement almost total recovery serum cerebrospinal fluid microbiological studies normaldiscussiondissimilar neurological injuries reported spinal anesthesia include 3 syndromes meningoencephalitis cranial nerve injury paraparesis plegia case 3 types lesions plus cerebral edemaconclusionsthe association three syndromes infrequent since find case databases resolution betamethasone therapeutic aspect consider similar caseskeywords encephalomyelitis anestesia spinal case reports,0.0
patient h syndrome cardiogenic shock multiorgan infiltration digital ischemia h syndrome hs rare autoinflammatory disease caused mutation solute carrier family 29 member 3 scl29a3 gene variable clinical presentation little phenotypegenotype correlati,0.0
propensitymatched comparison longterm disability worsening patients multiple sclerosis treated dimethyl fumarate fingolimod ther adv neurol disord 2021 jun 30 1417562864211021177 doi 101177 17562864211021177 ecollection 2021abstractbackground although aggregate data among patients multiple sclerosis ms shown similar efficacy dimethyl fumarate dmf fingolimod fty studies assessed longterm worsening disability compared longterm disability worsening 5 years assessed patientdetermined disease steps pdds among participants ms treated dmf ftymethods identified individuals north american research committee multiple sclerosis narcoms registry relapsingremitting ms rrms residing united states spring 2011 spring 2018 initiated treatment dmf n 689 fty n 565 1 year followup index treatment participants receiving dmf previously treated fty fty previously treated dmf excluded propensity score matching baseline used match ftytreated dmftreated participants time 6month confirmed disability worsening 1point increase pdds sustained 6 months estimated using cox regression sensitivity analysis conducted account differences duration index exposure dmf fty groupsresults propensity score matching 468 dmftreated participants matched 468 ftytreated participants median treatment duration 30 years dmf 40 years fty 5 years 683 95 confidence interval ci 624735 dmftreated participants 633 95 ci 596701 treated fty free 6month confirmed pdds worsening hazard ratio hr 101 95 ci 079128 p 095 results similar sensitivity analysis 705 95 ci 618776 dmftreated participants 727 95 ci 654786 ftytreated participants free 6month confirmed pdds worsening hr 104 95 ci 071151 p 084 conclusions participants ms narcoms registry significant difference confirmed disability pdds worsening 5 years treated dmf versus ftypmid34262613 pmcpmc8252399 doi101177 17562864211021177,0.0
regulation exosome secretion cellular retinoic acid binding protein 1 contributes systemic antiinflammation background intercellular communications important maintaining normal physiological processes important intercellular communication mediated exchange membraneenclosed extracellular vesicles among various vesicles exosomes can detected wide variety biological systems regulation biological implication exosome secretion uptake remains largely unclearmethodscellular retinoic acid ra binding protein 1 crabp1 knockout cko mice used vivo studies extracellular exosomes monitored cko mice relevant cell cultures including embryonic stem cell cj7 macrophage raw 2647 hippocampal cell ht22 using western blot flow cytometry receptor interacting protein 140 rip140 depleted crispr cas9mediated gene editing antiinflammatory maker analyzed using qrtpcr clinical relevance accessed mining multiple clinical datasetsresultsthis study uncovers crabp1 negative regulator exosome secretion neurons specifically rip140 proinflammatory regulator can transferred neurons via crabp1regulated exosome secretion macrophages promote inflammatory polarization consistently cko mice defected negative control exosome secretion significantly elevated rip140containing exosomes blood cerebrospinal fluid exhibit increased vulnerability systemic inflammation clinical relevance pathway supported patients data multiple inflammatory diseases action crabp1 regulating exosome secretion involves ligand mediated downstream target mapk signaling pathwayconclusionsthis study presents first evidence regulation exosome secretion mediates intercellular communication racrabp1 signaling novel mechanism can contribute control systemic inflammation transferring inflammatory regulator rip140 cells represents new mechanism vitamin action can modulate homeostasis systemwide innate immunity without involving gene regulation video abstract,0.0
increased extracellular fluid associated white matter fiber degeneration cadasil vivo evidence diffusion magnetic resonance imaging background white matter hyperintensities wmhs one hallmarks cerebral small vessel disease csvd pathological mechanisms underlying wmhs remain unclear recent studies suggest extracellular fluid ecf increased brain regions wmhs hypothesized ecf accumulation may detrimental effects white matter microstructure test hypothesis used cerebral autosomaldominant arteriopathy subcortical infarcts leukoencephalopathy cadasil unique csvd model investigate relationships ecf fiber microstructural changes wmhsmethodsthirtyeight cadasil patients underwent 30 t mri multimodel sequences parameters free water fw apparent fiber density afd obtained diffusionweighted imaging b 0 1000 s mm2 respectively used quantify ecf fiber density wmhs split four subregions four levels fw using quartiles fwq1 fwq4 participant analyzed relationships fw afd subregion wmhs additionally tested whether fw wmhs associated accompanied csvd imaging markers including lacunes microbleedsresultswe found inverse correlation fw afd wmhs subregions wmhs highlevel fw fwq3 fwq4 accompanied decreased afd changes fwcorrected diffusion tensor imaging parameters furthermore fw also independently associated lacunes microbleedsconclusionsour study demonstrated increased ecf associated wm degeneration occurrence lacunes microbleeds providing important new insights role ecf cadasil pathology improving ecf drainage might become therapeutic strategy future,0.0
neurite orientation dispersion density imaging reveals white matter microstructural alterations adults autism background evidences suggesting association behavioral anomalies autism white matter wm microstructural alterations increasing diffusion tensor imaging dti widely used infer tissue microstructure however due lack specificity underlying pathology reported differences dti measures autism remains poorly understood herein applied neurite orientation dispersion density imaging noddi quantify define specific causes wm microstructural changes associated autism adultsmethodsnoddi neurite density index ndi orientation dispersion index isotropic volume fraction isovf dti fractional anisotropy fa mean diffusivity md axial diffusivity radial diffusivity rd measures compared autism n 26 19 males 7 females 3293 924 years old age sexmatched typically developing td n 25 17 males 8 females 3443 902 years old groups using tractbased spatial statistics regionofinterest analyses linear discriminant analysis using leaveoneout crossvalidation ldaloocv also performed assess discriminative power diffusion measures autism tdresultssignificantly lower ndi higher isovf suggestive decreased neurite density increased extracellular freewater respectively demonstrated autism group compared td group mainly commissural longrange association tracts distinct predominant sides consistent previous reports autism group showed lower fa higher md rd compared td group notably ldaloocv suggests ndi isovf relatively higher accuracy 82 specificity ndi 84 isovf 88 compared fa md rd accuracy 6773 specificity 6880 limitationsthe absence histopathological confirmation limit interpretation findingsconclusionsour results suggest noddi measures might useful imaging biomarkers diagnose autism adults assess behavioral characteristics furthermore noddi allows interpretation previous findings changes wm diffusion tensor metrics individuals autism,0.0
oncofertility personalized testing potential loss ovarian reserve patients undergoing chemotherapy proposed next steps development genetic testing predict changes ovarian reserve abstractwomen reproductive age undergoing chemotherapy face risk irreversible ovarian insufficiency current methods ovarian reserve testing accurately predict future reproductive potential patients undergoing chemotherapy genetic markers accurately predict reproductive potential patient undergoing chemotherapy critical tools useful evidencebased fertility preservation counselling assess possible approaches take develop personalized genetic testing patients review current literature regarding mechanisms ovarian damage due chemotherapy genetic variants associated damage mechanisms primary ovarian insufficiency medical literature point number genetic variants associated mechanisms ovarian damage primary ovarian insufficiency variants appear higher frequency known pathways may considered potential genetic markers predictive ovarian reserve testing propose developing personalized testing potential loss ovarian function patients cancer prior chemotherapy treatment advantages using genetic markers complementary current ovarian reserve markers amh antral follicle count day 3 fsh predictors preservation fertility chemotherapy genetic markers will help identify upstream pathways leading high risk ovarian failure detected present clinical markers predictive value mechanismbased will encourage research towards understanding multiple pathways contributing ovarian failure chemotherapy,0.0
stat3 hif1 signaling activation mediates peritoneal fibrosis induced high glucose background epithelialmesenchymal transition emt mesothelial cells key step peritoneal fibrosis pf recent evidence indicates signal transducer activator transcription 3 stat3 might mediate process renal fibrosis induce expression hypoxiainducible factor1 hif1 investigated effect stat3 activation hif1 expression emt mesothelial cells furthermore role pharmacological blockade stat3 process pf peritoneal dialysis pd treatmentmethodsfirstly investigated stat3 signaling human peritoneal mesothelial cells hpmcs drained pd effluent secondly explored effect stat3 signaling activation emt expression hif1 human mesothelial cells met5a induced high glucose finally peritoneal fibrosis induced daily intraperitoneal injection peritoneal dialysis fluid pdf explore role pharmacological blockade stat3 processresultscompared new pd patient level phosphorylated stat3 upregulated peritoneal mesothelial cells longterm pd patients high glucose 60 mmol l induced overexpression collagen fibronectin sma reduced expression ecadherin met5a cells abrogated stat3 inhibitor s3i201 pretreatment well sirna stat3 furthermore high glucosemediated stat3 activation mesothelial cells induced expression hif1 profibrotic effect stat3 signaling alleviated sirna hif1 daily intraperitoneal injection highglucose based dialysis fluid hgpdf induced peritoneal fibrosis mice accompanied phosphorylation stat3 immunostaining showed phosphorylated stat3 expressed mostly sma positive cells peritoneal membrane induced hgpdf administration s3i201 prevented progression peritoneal fibrosis angiogenesis macrophage infiltration well expression hif1 peritoneal membrane induced high glucoseconclusionstaken together findings identified novel mechanism linking stat3 hif1 signaling peritoneal fibrosis longterm pd treatment provided first evidence pharmacological inhibition stat3 signaling attenuated high glucosemediated mesothelial cells emt well peritoneal fibrosis,0.0
using monoclonal antibody therapies multiple sclerosis review biologics 2021 jun 30 15255263 doi 102147 btts267273 ecollection 2021abstractmonoclonal antibody therapies secured important role therapeutic landscape treatment relapsing progressive forms multiple sclerosis due potent efficacy convenient dosing schedules welldefined side effect profiles therapy unique risks benefits associated specific mechanism action ultimately guides clinical decisionmaking individual patients review will summarize mechanisms action evidence leading approval clinically relevant considerations current monoclonal antibody therapies approved treatment multiple sclerosispmid34234409 pmcpmc8255409 doi102147 btts267273,0.0
downregulation bcl2l13 renders poor prognosis clear cell papillary renal cell carcinoma background bcl2l13 belongs bcl2 super family protein product exhibits capacity apoptosismediating diversified cell lines previous studies shown bcl2l13 functional consequence several tumor types including gbm however function kidney cancer remains yet unclearlymethodsmultiple webbased portals employed analyze effect bcl2l13 kidney cancer using data tcga database functional enrichment analysis hubs bcl2l13 coexpressed genes clear cell renal cell carcinoma ccrcc papillary renal cell carcinoma prcc carried cytoscape evaluation bcl2l13 protein level accomplished immunohistochemistry paraffin embedded renal cancer tissue sections western blotting flow cytometry implemented analyze proapoptotic function bcl2l13 ccrcc cell line 7860resultsbcl2l13 expression significantly decreased ccrcc prcc patients however mutations copy number alterations rarely observed poor prognosis ccrcc derived downregulated bcl2l13 independent patients gender tumor grade furthermore bcl2l13 weakly correlates genes mutated kidney cancer genes associated inherited kidney cancer predisposing syndrome actively correlates slc25a4 downstream effector bcl2l13 proapoptotic pathway slc25a4 found one hub genes involved physiological function bcl2l13 kidney cancer tissuesconclusionsdownregulation bcl2l13 renders poor prognosis ccrcc prcc disadvantageous factor independent wellknown kidney cancer related genes bcl2l13 can used effective indicator prognostic evaluation renal cell carcinoma,0.0
transcultural adaptation psychometric properties family quality life survey caregivers people neurodegenerative disease study spanish families live rural spainportugal crossborder background neurodegenerative diseases nds one main causes disability dependence great impact quality life people disabilities families majority people nds receive care support family tool spain measure wholefamily qol aim study translation cultural adaptation validation fqolsdementia spanish assess fqol among family members individuals nds live spainportugal crossborder areamethodthe spanish version translated adapted following international guidelines crosscultural adaptation tests sample 300 family caregivers interviewed applying adapted version family quality survey fqolsdementia confirmatory factor analysis performed validate factor structure convergent validity examined pearsons correlation coefficients global fqol domains internal consistency reliability determined using cronbachs alpharesultsthe domain structure fqolsnd showed good fit convergent validity found total score subscale domain scores associated global fqol score except values domain internal consistency nine domain subscales strong 080 091 excellent total fqol 085 global fqol 087 conclusionthe fqolsnd presented good validity reliability caregiver families individuals nd application shows usefulness detecting areas improvement intervention strategies fqol spainportugal crossborder area,0.0
potential prognostic value circulating inflammamir146a5p 125a5p relapsingremitting multiple sclerosis abstractbackgroundinflammamirs group micrornas involved regulation innate adaptive immune responses increasing evidence support contribution dysregulated inflammamirs pathogenesis multiple sclerosis aim study evaluate expression selected inflammamirs ie mir34a5p 125a5p 146a5p 155 relapsingremitting multiple sclerosis rrms modulation treatment dimethyl fumarate dmf methodscirculating levels micrornas involved inflammatory response inflammamirs compared healthy controls ctrs n21 patients rrms n24 started treatment dmfresultsplasma levels mir34a p0001 mir125a5p p0034 higher whereas mir146a5p levels lower p0041 rrms patients compared ctrs circulating mir125a5p p0001 mir146a5p p0001 mir155 p0013 reduced 4month treatment dmf among baseline 4month follow mir125a5p p0028 mir146a5p p0042 levels related disability progressionconclusioncirculating inflammamirs represent candidate tools predict ms clinical course evaluate effectiveness diseasemodifying treatments rrms,0.0
correction data sharing goals nonprofit funders clinical trials j particip med 2021 jun 30 13 2 e31371 doi 102196 31371abstract corrects article doi 102196 23011 pmid34255670 doi102196 31371,0.0
win odds adaptation win ratio include ties stat med 2021 apr 16 doi 101002 sim8967 online ahead printabstractthe win ratio recently proposed measure comparing benefit two treatment groups allows ties data ignores ties inference article highlight difficulties can lead propose focus win odds instead modification win ratio takes ties account construct hypothesis tests confidence intervals win odds investigate properties simulations case study conclude win odds preferred win ratiopmid33860957 doi101002 sim8967,0.0
association visual attention body movementcontrolled video games balance mobility older adults background body movementcontrolled video games involving physical motion visual attention may potential train abilities simultaneously purpose determine associations performance games visual attention balance mobility group older adults longterm goal identify optimal type interactive games regards training potentialmethodsfifty healthy adults aged 65+ years participated crosssectional study visual attention measured static dynamic versions useful field view ufv multiple object tracking mot test balance measured force plate bipedal quiet stance test qst onelegged stance olst gait variability walking speed assessed five meter walk test 5mwt four microsoft xbox 360 kinect interactive video games chosen based apparent levels visual attention demandresultsvisual attention ufv mot significantly associated performance xbox kinect games appeared high visual attention demand p 005 minimal significant association games apparent low visual attention demand balance mobility show correlations visual attention xbox gamesconclusionthe results suggest relationships visual attention balance mobility xbox kinect game performance since different xbox games associated different balance mobility visual attention scores variety games rather single game may effective training falls prevention,0.0
chitinaselike protein ym2 chil4 regulates regeneration olfactory epithelium via interaction inflammation adult olfactory epithelium oe regenerates sensory neurons nonsensory supporting cells resident stem cells injury supporting cells contribute oe regeneration remains largely unknown study elucidated novel role ym2 also known chil4 chi3l4 chitinaselike protein expressed supporting cells regulating regeneration injured oe vivo male female mice cell proliferation differentiation oe colonies vitro found ym2 expression enhanced supporting cells oe injury genetic knockdown ym2 supporting cells attenuated recovery injured oe ym2 overexpression lentiviral infection accelerated oe regeneration similarly ym2 bidirectionally regulated cell proliferation differentiation oe colonies furthermore antiinflammatory treatment reduced ym2 expression delayed oe regeneration vivo cell proliferation differentiation vitro counteracted ym2 overexpression collectively study revealed novel role ym2 oe regeneration cell proliferation differentiation oe colonies via interaction inflammatory responses providing new clues function supporting cells processessignificance statement mammalian olfactory epithelium oe unique neural tissue regenerates sensory neurons nonsensory supporting cells throughout life postinjury supporting cells contribute process entirely understood report oe injury causes upregulation chitinaselike protein ym2 supporting cells facilitates oe regeneration moreover antiinflammatory treatment reduces ym2 expression delays oe regeneration counteracted ym2 overexpression study reveals important role supporting cells oe regeneration provides critical link ym2 inflammation process,0.0
lipidomics study plasma patients suggest als pls part continuum motor neuron disorders sci rep 2021 jun 30 11 1 13562 doi 101038 s41598021921123abstractmotor neuron disorders mnd include group pathologies affect upper lower motor neurons among amyotrophic lateral sclerosis als characterized progressive muscle weakness fatal outcomes years diagnosis hand primary lateral sclerosis pls benign form mnd affects upper motor neurons results lifelong progressive motor dysfunction although outcomes quite different als pls present similar symptoms disease onset degree disorders considered part continuum similarities lack reliable biomarkers often result delays accurate diagnosis treatment nervous system lipids exert wide variety functions including roles cell structure synaptic transmission multiple metabolic processes thus study absolute relative concentrations subset lipids human pathology can shed light cellular processes unravel alterations one pathways report lipid composition longitudinal plasma samples als pls patients initially 2 years following enrollment clinical study analysis revealed common aspects pathologies suggesting lipidomics point view pls als behave part continuum motor neuron disorderspmid34193885 doi101038 s41598021921123,0.0
coultramicronized palmitoylethanolamide luteolininduced oligodendrocyte precursor cell differentiation associated tyro3 receptor upregulation front pharmacol 2021 jun 30 12698133 doi 103389 fphar2021698133 ecollection 2021abstractremyelination patients multiple sclerosis frequently fails especially chronic phase disease promoting axonal neuronal degeneration progressive disease disability drugbased therapies able promote endogenous remyelination capability oligodendrocytes thus emerging primary approaches multiple sclerosis recently reported coultramicronized composite palmitoylethanolamide flavonoid luteolin pealut promotes oligodendrocyte precursor cell opc maturation without affecting proliferation since tam receptor signaling reported important modulator oligodendrocyte survival evaluated eventual involvement tam receptors pealutinduced opc maturation mrnas related tam receptors tyro3 axl mertk present day 2 vitro however tyro3 gene expression significantly increased upon cell differentiation axl mertk change first week vitro tyro3 gene expression developmental pattern resembled mbp myelin protein opcs treated pealut developmental increase tyro3 mrna significantly higher compared vehicle reduced gene expression related axl mertk rapamycin inhibitor mtor prevented oligodendrocyte growth differentiation myelination pealut administered cultures 30 min rapamycin prevented alteration mrna basal expression tam receptors well expression myelin proteins mbp cnpase altogether data obtained confirm pealut promotes oligodendrocyte differentiation shown increase mbp cnpase tyro3 mrnas well cnpase tyro3 immunostainings finding effects reduced opcs exposed rapamycin suggests involvement mtor signaling pealut effectspmid34276381 pmcpmc8277943 doi103389 fphar2021698133,1.0
antibody testing neurological autoimmune disorders evaluation best practices tertiary referral center front neurol 2021 jun 30 12690415 doi 103389 fneur2021690415 ecollection 2021abstractbackground autoimmune neurology rapidly evolving field study best practices neurological antibody testing yet determined growing number options antibody panel testing can create confusion amongst ordering clinicians lead ordering several concurrent panels ie overlapping evaluations repeat panel evaluations study determined frequency evaluations autoimmune paraneoplastic disorders investigated practices informed clinical decision making management methods retrospective observational study adult patients presenting university texas southwestern utsw 2017 requests antibody panels autoimmune encephalitis paraneoplastic disorders individuals one panel requested defined either overlapping evaluation one panel requested within 14 days repeat evaluation one panel requested 14 days apart individuals repeat panel testing proportion panels change antibody status subsequent changes clinical diagnosis decision making recorded results total 813 panels sent 626 individuals twenty percent 126 individuals one panel requested 10 individuals matched serum csf evaluation fortyseven overlapping evaluations performed 46 73 individuals studied fiftyfour 86 individuals underwent 70 repeat evaluations encompassing 79 panels 97 total panels ordered ten repeat evaluations showed change antibody status two clinically significant single case clinical management affected repeat autoantibody evaluation conclusions ordering practices suspected autoimmune encephalitis paraneoplastic disorders suboptimal frequent overlapping antibody panel evaluations nonpaired serum csf samples center repeat autoantibody testing commonplace practice yet yielded novel information minority cases new results rule clinically irrelevant changed clinical decision making 1 cases limited utility practice patterns future efforts directed development standardization neurological autoimmune paraneoplastic autoantibody testing practice standardspmid34276541 pmcpmc8277913 doi103389 fneur2021690415,0.0
adolescentonset antimda5 antibodypositive juvenile dermatomyositis rapidly progressive interstitial lung disease spontaneous pneumomediastinum case report literature review background dermatomyositis positive antimelanoma differentiationassociated gene 5 antimda5 antibody distinct phenotype associated small hand joint arthritis mucocutaneous ulceration palmar papules less muscle involvement also associated increased risk rapidly progressive interstitial lung disease rpild high mortality rate adults evidence cases complicated spontaneous pneumomediastinum pnm increase mortality evidence rare disease derived adult literature report case diagnosed adolescent complicated rpild pnm good outcome aggressive immunosuppressive therapy case also illustrates potential challenges diagnosis condition setting nonspecific clinical manifestations need high index suspicion importance testing myositisspecific antibodies msa early aid diagnosis given risk rapid progression patientscase presentationa 16yearold chinese female presented fever cough 1 day finger swelling 3 weeks physical examination revealed arthritis fingers wrists ulcers palmar papules fingers hyperpigmentation interphalangeal joints rash neck diagnosis dermatomyositis made 1 month later onset malar rash gottrons papules calcinosis myalgia diagnosis supported presence antimda5 antibody evidence inflammatory myopathy magnetic resonance imaging retrospect already interstitial lung disease first presentation manifested cough opacity chest radiograph later confirmed chest computed tomography treated according adult guidelines steroid calcineurin inhibitor disease resistant initial therapy complicated rpild spontaneous pnm intensive immunosuppressive therapy including cyclophosphamide rituximab required induce remissionconclusionsrecognition distinct clinical features antimda5 antibodypositive dermatomyositis testing msa crucial patients skin ulceration abnormal pulmonary findings unknown etiology prompt diagnosis early aggressive treatment anticipation complications make difference outcome disease high mortality,0.0
plant derived cyclic peptides biochem soc trans 2021 jun 22bst20200881 doi 101042 bst20200881 online ahead printabstractcyclic peptides widespread throughout plant kingdom display diverse sequences structures bioactivities potential applications attributed peptides unusual biosynthesis captivated attention researchers many years several gene sequences plant cyclic peptides discovered last two decades recently beginning understand intricacies associated biosynthesis recent studies focussed three main classes plant derived cyclic peptides namely orbitides sfti related peptides cyclotides minireview discuss expansion known sequence structural diversity families insights enzymes involved biosynthesis exciting applications includes cyclotide currently clinical trials treatment multiple sclerosis new production methods developed realise potential plant cyclic peptides pharmaceutical agricultural agentspmid34156400 doi101042 bst20200881,0.0
crosssectional cohort study activity turnover neutrophil granulocytes juvenile idiopathic arthritis background inflammatory process juvenile idiopathic arthritis jia involves innate adaptive immune system turnover activity neutrophil granulocytes may reflected proteins secreted primary secondary granules cytoplasm sequestered cells primary aim compare levels secondary neutrophil granule protein human neutrophil lipocalin hnl jia patients controls explore possible priming neutrophils parallel analyses plasma serum secondary aim relate levels hnl two wellstudied leukocyte proteins s100a8 a9 myeloperoxidase mpo well clinical aspects jiamethodsthe concentrations three biomarkers serum two also plasma measured using enzymelinked immunosorbent assay 37 children jia without medical treatment high disease activity based juvenile arthritis disease activity score 27 jadas27 32 children medical treatment mainly lower disease activity 16 healthy children assessed differences two groups using mannwhitney u test used kruskalwallis test multiple group comparisons spearman rank correlation linear multiple regression analyses used evaluation associations biomarker concentrations clinical scoresresultsthe concentrations hnl mpo serum significantly increased children jia p 0001 p 0002 compared healthy children found difference plasma levels hnl mpo children jia controls serum concentrations mpo hnl unaffected medical treatment s100a8 a9 reduced medical treatment correlated jadas27 univariate r 058 p 0001 multivariate r 059 p 0001 analysesconclusionsneutrophil granulocytes children jia primed release primary secondary granule proteins without relation medical treatment whereas signs increased turnover sequestration neutrophil granulocytes reduced treatment levels neutrophiloriginating proteins serum likely reflect underlying disease activities jia,0.0
increased cerebrospinal fluid adenosine 5#39 triphosphate patients amyotrophic lateral sclerosis background extracellular adenosine 5triphosphate atp suggested cause neuroinflammation motor neuron degeneration activating microglia astrocytes amyotrophic lateral sclerosis als since developed highly sensitive atp assay system examined cerebrospinal fluid csf atp levels patients als whether can useful biomarker alsmethodsfortyeight csf samples 44 patients als assayed atp newly established highly sensitive assay system using luciferase luminous reaction csf samples patients idiopathic normal pressure hydrocephalus inph assayed control patients divided two groups depending disease severity evaluated using medical research council mrc sum score correlations csf atp levels factors including clinical data serum creatinine levels evaluatedresultscsf atp levels significantly higher patients als inph 716 411 vs 3635 5465 pmol l p 001 csf atp levels significantly higher severe group inph group 6860 8312 vs 716 411 pmol l p 005 mild group 6860 8312 vs 2676 3959 pmol l p 005 respectively als functional rating scalerevised alsfrsr 379 57 vs 424 28 p 001 serum creatinine levels 051 013 vs 068 023 mg dl p 005 significantly lower severe group mild group respectively negative correlation csf atp levels mrc sum score demonstrated correlation analysis adjusted age sex r 03 p 008 conclusionsextracellular atp particularly increased csf patients advanced als csf atp levels may useful biomarker evaluating disease severity patients als,0.0
investigating interaction fertility pregnancy multiple sclerosis j educ health promot 2021 jun 30 10220 doi 104103 jehpjehp_1107_20 ecollection 2021abstractbackground multiple sclerosis ms chronic disease central nervous system women ms diagnosed reproductive ages aim study evaluate interaction fertility pregnancy msmaterials methods retrospective descriptiveanalytic study conducted 110 women suffering ms history pregnancy 2007 2017 years isfahan iran samples selected census model women completed researcherconstructed questionnaire telephone questionnaire consisted three parts demographic information ms symptoms treatment reproductive system history pregnancy associated ms data analyzed spss software version 16 using chisquare anova ttestresults mean age women 324 years population average number pregnancies 161 number deliveries 135 number abortions 024 history ectopic pregnancy 001 number alive children 136 number dead children 001 average time last ms attack pregnancy 2136 months fatigue 245 common symptom exacerbated pregnancy ms symptoms improved 550 women second trimesterconclusions ms effect pregnancy status number abortions ectopic pregnancy alive dead children duration pregnancy symptoms disease improved pregnancy therefore pregnancy protective role mspmid34395657 pmcpmc8318175 doi104103 jehpjehp_1107_20,0.0
increased expression plasma mirna320a let7b5p heroindependent patients clinical significance front psychiatry 2021 jun 29 12679206 doi 103389 fpsyt2021679206 ecollection 2021abstractheroin use disorder chronic relapsing disease induces persistent changes brain diagnoses heroin use disorders mainly based subjective reports valid biomarkers available recent researches revealed circulating mirnas useful noninvasive biomarkers diagnosing brain diseases alzheimers disease multiple sclerosis schizophrenia bipolar disorder however studies circulating mirnas diagnosis heroin use disorders rarely reported study investigated differential expression plasma mirnas 57 heroindependent patients based literature research microarray analysis two candidate mirnas mir320a let7b5p selected analyzed quantitative realtime rtpcr results showed mir320a let7b significantly upregulated plasma heroindependent patients compared healthy controls area curves aucs receiver operating characteristic roc curves mir320a let7b5p 0748 0758 respectively sensitivities mir320a let7b5p 719 702 specificities mir320a let7b5p 761 783 respectively combination two mirnas predicted heron dependence auc 0782 95 ci 06870876 737 sensitivity 826 specificity findings suggest potential use circulating mirnas biomarkers diagnosis heroin abusepmid34267687 pmcpmc8275879 doi103389 fpsyt2021679206,0.0
micrornas emerging driver cancer perineural invasion abstractthe perineural invasion pni refers tumor cells encroaching nerve clinical feature frequently occurred various malignant tumors responsible postoperative recurrence metastasis decreased survival pathogenesis pni switches lowresistance channel hypothesis mutual attraction theory peripheral nerves tumor cells perineural niche among various molecules perineural niche microrna mirna emerging modulator pni generating rnainduced silencing complex risc orchestrate oncogene antioncogene aroused wide attention article systematically reviewed role microrna pni promising identify new biomarkers offer cancer therapeutic targets,0.0
changes health care people multiple sclerosis latin america covid19 pandemic abstractbackgroundthe covid19 pandemic resulted uncertain access medical treatment people multiple sclerosis pwms world however data regarding impact access health care pwms latin americaobjectiveswe investigated described changes health care delivery pwms latin america covid19 pandemicmethodspwms 18 patient organizations region completed webbased survey hosted may october 2020resultsa total 602 pwms completed questionnaire changes diseasemodifying therapies dmts use 67 pwms continuous dmts claimed stopped 141 infusion therapies declared postpone dosing 688 declared delaying initiation dmt disruptions accessing rehabilitation services reported 657 changes laboratory mri monitoring reported 30 33 respectively multivariableadjusted logistic regression model changes laboratory monitoring significantly associated increased odds postponing mri monitoring 409 ci95 279600 p0001 conclusionsthe covid19 pandemic disrupted aspects routine care pwms latin america consequences yet determined,0.0
internetbased survey synesthesia multiple sclerosis incidence characteristics implications abstractobjective prior work raises interesting possibility multiple sclerosis synesthesia share common etiology immune system dysfunction well neuroanatomical neurochemical abnormalities including involving white matter serotonergic pathways respectively given links two syndromes examined possibility prevalence synesthesia elevated population individuals ms relative thought prevalence neurotypical population known whether synesthesia might marker subsequent development ms synesthesia might reflect neurological damage resulting ms disease progression method individuals self reported clinically definite ms recruited online via internet social media using sites specifically relevant ms community data 147 individuals completed several questionnaires related synesthesia analyzed results depending criteria approximately 7 16 individuals ms reported synesthesia estimated 157 355 times increased incidence synesthesia relative previous findings neurotypical samples limitations study include internet survey synesthesia directly assessed sample conclusions results suggest link syndromes primarily indicating synesthesia may marker subsequent ms development implications directions future study discussed,0.0
validating walking talking test measure motor cognitive dualtask performance ambulatory individuals multiple sclerosis abstractintroductionmultiple sclerosis ms associated demyelination central nervous system negatively impacts motor cognitive function resulting difficulty performing simultaneous motor cognitive tasks dualtasks declines dualtasking linked falls ms thus dualtask assessment walking talking test wwtt commonly utilized clinical setting however validity minimal detectable change mdc wwtt established persons ms primary objective study establish wwtt valid measure dualtask function examining concurrent validity motor cognitive dualtask measures establish mdc simple complex conditions wwttmethodsin single visit 38 adults 34 female mean sd age 498 91 patient determined disease steps pdds mean 3 range 16 completed wwtt simple walk reciting alphabet complex walk reciting every letter alphabet conditions well battery cognitive motor tests spearman correlations used examine concurrent validity sample divided low high disability groups determine impact disability severity relationships among wwtt cognitive motor functionresultsexcellent concurrent validity r079 p0001 observed wwtt simple complex motor timed upandgo timed 25foot walk forward backward walking velocity sixspot step test dualtask measures timed upandgo cognitive wwttsimple demonstrated moderate concurrent validity measures processing speed symbol digit modalities test p0041 related motor dualtask measures across disability levels wwtt complex related complex motor tasks low disability group within low disability group wwtt associated processing speed p0045 working memory california verbal learning test p0012 mdc values established wwtt simple 69s complex 8s conditionsdiscussionthe wwtt quick easytoadminister clinical measure captures motor cognitive aspects performance persons ms clinicians consider adding wwtt evaluation persons ms examine dualtask performance,1.0
upregulation selected hervw loci multiple sclerosis abstract introductionhuman endogenous retrovirus herv present day versions retroviral germline infections occured millions years ago occupy 8 genome 1 mostly replication deficient known express rna protein 2 particular developmental stages response aging 3 inflammation wide range pathologies 4 human retrovirus discovered multiple sclerosis ms patients 5 turned prototype novel herv family referred hervw 6 hervw family consists 213 elements 12 complete proviral copies intact ltrs 7 increased expression hervw peripheral blood mononuclear cells pbmcs repeatedly associated ms presence hervw protein elevated rna transcription correlated disease activity 8 9 10 contribution hervwencoded proteins brain disease suggested presence msassociated brain lesions expression peripheral organs may involved disease process cytokineinduced damage blood brain barrier subsequent infiltration monocytes alterations peripheral expression may also serve useful practical marker diagnostics cns disease therefore quantified overall hervw levels identified individual hervw loci actually transcribed pbmcs analysis carried patients diagnosed clinically isolated syndrome cis precursor ms defined single episode neurologic symptoms lasting least 24 h cis indicator future development ms 60 people diagnosed cis develop ms 11 patients potentially represent earliest stage ms routinely available clinical analysis undertook next generation sequencing ngs based analysis transcripts amplified cdna obtained patients cis samples healthy controls data presented pilot experiment indicate relative frequency specific hervw copies altered pbmc cis patients even absence overall hervw overexpression altered frequency appears derived less abundantly transcribed potentially msrelated hervw locimethodspatients table 1 local ethics committee ceica approved study protocol cp ci pi14 0021 dated 26 02 2014 modified 25 10 2017 patients provided written informed consent protocolo y informacin para el paciente v2 de 29 12 2013 blood samples collected ms patients healthy controls neurology department miguel servet university hospital zaragoza spain whole fresh blood drawn vacutainer tubes becton dickinson vacutainer containing edta within 24 h pbmc isolated previously described 12 13 table 1 clinical features ms patients included studyfull size tableexpression analysis pcrrna isolation randomprimed cdna synthesis 14 carried described hervw env levels determined triplicate qpcr assays described 14 15 identification localization transcribed hervw loci cdna amplified employing external primers established pcr assay hervw env 15 products purified subjected ngs analysisngs analysislibrary preparation sequencing carried using iontorrent technology workflow ion torrent s5xl platform using ion 530 chip resulting reads mapped human reference genome version hg19 using strict criteria maximize mapping differences different hervw copies relative frequencies calculated number reads mapping individual hervw env element relative total number reads details suppl methodsstatistical analysisspss software used analyses graphs version 150 normality statistical significance differences assessed using specific tests data analyzed using deseq2 package 16 correct p values multiple testing false discovery rate005 detailed information available suppl mmresultswe carried hervw env expression analyses using optimized assay described mameli et al 15 significantly increased expression hervw detected small cohort cis patients n6 compared agematched controls n15 umannwhitney p0267 fig 1 results skewed use gapdh reference gene fig 1 comparison rpl19 hsda reference genes table s1 suppl figure 1 showed statistical difference use either gapdh mean three genes welchs ttest p005 fig 1figure1hervw expression levels cis patients expression analysis hervw env levels cis n6 patients nondiseased individuals n15 ndi controls analyzed qpcr results normalized using gapdh reference gene represented fold expression compared median expression level controls recalculated percentage umannwhitney test p 0267full size imagein absence increased overall expression levels hervw cis samples wondered whether specific copies hervw table s2 might differentially expressed performed ngs analysis identify individual hervw copies altered expression pbmc cis patients n5 controls n5 reads obtained 70 69424 812 per sample 25 286136 704 mapped human genome assigned unique genomic locations reads corresponding 39 hervw env loci extracted table s3 table 2 expected 9985 mapped reads correspond 39 loci analyzed data shown resulting data showed reads obtained cis patients mapped significant higher number different hervw env loci 3113 compared obtained controls 1655 tstudent p0018 fig 2 70 reads mapped either two loci 19q132 xq223 extending range reads mapped high frequency 36 total reads locus limited number loci particular hervw env copies located chromosomes 19q132 xq223 8q2111 15q213 12q233 4q2122 fig 2 b found significant differences cis patients controls relative frequency reads mapping loci fig 2 b table 2 table 2 percentages reads mapped individual hervw locifull size tablefig 2figure2ngs analysis transcribed hervw env copies pbmcs specific msrv env pcr assay 15 applied random primed cdna cis patients n5 controls n5 products sequenced ngs sample relative frequency reads mapping individual hervw env copies calculated relative total number mapped reads total number transcribed hervw env copies identified p0018 students t test b individual hervw env copies mean relative frequency reads mapping copy represented pie charts abundantly transcribed copies indicated ce median relative frequency reads mapped individual hervw env copies cis patients controls indicatedfull size imagelower numbers reads mapped remaining 33 loci relative frequencies ranging 0 01 1 66 found differences cis patients controls relative frequency reads mapping several reads mapping subset hervw loci including copy_chr31 copy_chr43 copy_chr51 copy_chr91 copy_chr92 copy_chr124 copy_chr191 differed cis patients controls table 3 fig 2 ce relative frequency ranging 0 32 95 reads mapping loci showed a7 fold increase cis patients compared controls table 3 corrected multilocus analysis significant differential expression p005 fdr005 five loci loci evident table 3 significant increases expression hervw copies 3q1121 4q311 9q313 19p12 significant decrease 12q233table 3 hervw copies differentially expressed cis patientsfull size tablediscussionin contrast small group cis patients analyzed study increased hervw levels associated frequently ms inability demonstrate statistically significant increase overall hervw levels pbmc cis patients may explained selection particular group likely simply small sample size however lack increased expression unprecedented previously reported cohort south african ms patients although different primers used analysis 17 perfomed ngs analysis identify individual hervw copies show altered expression pbmc comparing cis patients n5 controls n5 although definite answers require future analysis subjects cis patients analyzed hervw loci expressed control subjects similar increase reported previously ms brain 18 previous studies failed identify msspecific loci expression 18 19 cis patients found statistically significant overrepresentation reads corresponding specific loci ie 3q112 19p12 see table 3 complete list locusspecific qpcr assays may first help confirm finding larger patient cohort subsequently evaluated potential prognostic assaythese combined overrepresented loci produce 13 total transcripts fig 2 ce combined findings low levels overexpression activation loci activation lowexpressing hervw elements cis patients suggest potential contribution pathology may unrelated overall high expression levels none copies identified encode fulllength env protein sequences corresponding env gene truncated lack atg codons carry frame shifts stop codons suppl figure 2 cisassociated copies may produce proteins either envrelated especially active activation tlr4 20 rnas trigger native immune system tlr3 21 22 although analysis shows upregulation specific hervw loci pbmc associated cis presence transcripts ms brain unknown present potential role transcripts proviral protein production activation either peripheral immune system cns disease remains establishedavailability data materialsthe datasets used analyzed study deposited ncbis gene expression omnibus edgar et al 2002 accessible geo series accession number gse173929 https wwwncbinlmnihgov geo query acccgiaccgse173929,0.0
susceptibility weighted imaging detects prominent veins precede coincide maximal motor disability model multiple sclerosis pilot study abstractbackgroundsusceptibility weighted imaging swi detected veins center white matter lesions alterations veins multiple sclerosis ms experimental autoimmune encephalomyelitis eae however relationship swidetected venous alterations disease progression unclear objective study assess alterations lumbar spinal cord veins eae mice disease course using serial swimethodseae mice n8 underwent imaging swi using 94t bruker avance console baseline 7 days premotor dysfunction 12 days typical motor dysfunction onset 1618 days typical peak disease postimmunization nave controls imaged alongside eae mice n3 swi hypointensities counted two subjects compared time pointsresultsswi hypointensities appeared motor dysfunction onset eae mice ratio swi hypointensities baseline highly variable eae mice 045675 less controls 080131 time point maximum number swi hypointensities always preceded coincided maximum motor disabilityconclusionvenous alterations detected onset motor disability eae mice using swi may relate inflammation tissue hypoxia,1.0
comprehensive highthroughput metaanalysis differentially expressed micrornas transcriptomic datasets reveals significant disruption mapk jnk signal transduction pathway adult tcell leukemia lymphoma background human tlymphotropic virus 1 htlv1 infection may lead development adult tcell leukemia lymphoma atll elucidate pathophysiology aggressive cd4+ tcell malignancy performed integrated systems biology approach analyze previous transcriptome datasets focusing differentially expressed mirnas dems peripheral blood atll patientsmethodsdatasets gse28626 gse31629 gse11577 used identify atllspecific dem signatures target genes identified mirna obtained construct proteinprotein interactions network using string database target gene hubs subjected analysis demonstrate significantly enriched gene ontology terms signaling pathways quantitative reverse transcription polymerase chain reaction rtqpcr performed major genes certain pathways identified network analysis highlight gene expression alterationsresultshighthroughput silico analysis revealed 9 dems hsalet7a hsalet7g hsamir181b hsamir26b hsamir30c hsamir186 hsamir10a hsamir30b hsalet7f atll patients healthy donors analysis revealed first 5 dems directly associated previously identified pathways pathogenesis htlv1 network analysis demonstrated involvement target gene hubs several signaling cascades mainly mapk pathway rtqpcr human atll samples showed significant upregulation evi1 mkp1 ptprr jnk gene vs healthy donors mapk jnk pathwaydiscussionthe results highlighted functional impact subset dysregulated micrornas atll cellular gene expression signal transduction pathways studies needed identify novel biomarkers obtain comprehensive mapping deregulated biological pathways atll,0.0
distinct patterns mri lesions mog antibody disease aqp4 nmosda systematic review metaanalysis abstractbackgroundthe distinct mri features mogantibody disease mogad aqp4nmosd still poorly defined performed systematic review metaanalysis identify specific patterns mri abnormalities able discriminate mogad aqp4nmosdmethodsfourteen caseseries 1028 patients included outcomes mri lesion patterns optic nerve brain spinal cord sc selected systematic literature review analysed separately event rate individual mri lesions mogad experimental group aqp4nmosd control group using random effect modelresultsmogad showed higher number mri lesions aqp4nmosd patients retrobulbar or567 95ci2111524 p00006 head swelling or820 95ci4131628 p000001 corpus callosum or230 95ci111476 p002 pons or287 95ci145567 p0002 lumbar conus sc or347 95ci166724 p00009 conversely lesions canalicular or042 95ci018098 p005 intracranial or030 95ci011084 p002 area postrema or012 95ci002061 p001 medulla or040 95ci020078 p0007 cervical sc or029 95ci009092 p004 prominent patients aqp4nmosd participantsnull age found source heterogeneity across studiesconclusionour study provides evidence mogad aqp4nmosd distinct mri features may help clinicians early differential diagnosis,0.0
paraneoplastic cerebellar degeneration platinumresponsive endometrial cancer case report review literature gynecol oncol rep 2021 jun 29 37100826 doi 101016 jgore2021100826 ecollection 2021 augabstractparaneoplastic cerebellar ataxia rare immuneinduced nonmetastatic neurologic syndrome frequently associated gynecological cancers carries abysmal prognosis report case patient advancedstage uterine cancer developed severe pancerebellar ataxia partial remission completion 3 cycles neoadjuvant platinumbased chemotherapy swift initiation immunosuppressive therapy corticosteroids combined plasmapheresis result significant clinical benefit early recognition debilitating condition standardization treatment strategy prerequisites improved survival outcomes quality life patients studies warranted clarify immunestimulating impact effective cytotoxic chemotherapy occurence autoimmune paraneoplastic neurological syndromespmid34258363 pmcpmc8260878 doi101016 jgore2021100826,0.0
therapeutic effects catechins less common neurological neurodegenerative disorders nutrients 2021 jun 29 13 7 2232 doi 103390 nu13072232abstractin recent years neurological neurodegenerative disorders research focused altered molecular mechanisms search potential pharmacological targets eg imbalances mechanisms response oxidative stress inflammation apoptosis autophagy proliferation differentiation migration neuronal plasticity occur less common neurological neurodegenerative pathologies huntington disease multiple sclerosis fetal alcohol spectrum disorders syndrome assess effects different catechins particularly epigalocatechin3gallate egcg disorders well use attenuating agerelated cognitive decline healthy individuals antioxidant free radical scavenging properties egcg due phenolic hydroxyl groups well immunomodulatory neuritogenic autophagic characteristics makes catechin promising tool neuroinflammation microglia activation common pathologies although egcg promotes inhibition protein aggregation experimental huntington disease studies improves clinical severity multiple sclerosis animal models efficacy humans remains controversial egcg may normalize dyrk1a involved neural plasticity overproduction syndrome improving behavioral neural phenotypes neurological pathologies caused environmental agents fasd egcg enhances antioxidant defense regulates placental angiogenesis neurodevelopmental processes demonstrated animal models catechins attenuate agerelated cognitive decline results improvements longterm outcomes working memory reduction hippocampal neuroinflammation enhancement neuronal plasticity however studies needed catechins valuable compounds treating preventing certain neurodegenerative neurological diseases genetic environmental origin however use different doses green tea extracts egcg makes difficult reach consistent conclusions different populationspmid34209677 doi103390 nu13072232,0.0
spectraldomain optical coherence tomography assessment treatmentnaive patients clinically isolated syndrome different multiple sclerosis types findings relationship disability status j clin med 2021 jun 29 10 13 2892 doi 103390 jcm10132892abstractthis study evaluates peripapillary retinal nerve fiber layer prnfl thickness total macular volume tmv using spectraldomain optical coherence tomography treatment nave patients clinically isolated syndrome cis different multiple sclerosis ms types total 126 patients 15 cis 65 relapsingremitting ms 14 secondary progressive ms 11 primary progressive ms 21 benign ms without optic neuritis history 63 healthy agesimilar controls assessed concerning controls eyes prnfl thickness significantly reduced cison eyes p 001 tmv prnfl thickness decreased ms eyes regardless history p 001 significant differences prnfl thickness tmv ms variants observed nonon eyes p 001 lowest values benign secondary progressive disease type respectively prnfl thickness inversely correlated expanded disability status scale edss score nonon subgroups p 001 whereas tmv inversely correlated edss score nonon subgroups p 001 concluding prnfl thinning confirms optic nerve damage cison eyes appears disproportionately high respect disability status benign ms patients values tmv prnfl nonon eyes significantly correspond ms course heterogeneity patients disability eyespmid34209692 doi103390 jcm10132892,0.0
multiple sclerosis epidemiology asia oceania systematic review metaanalysis abstractbackgroundmultiple sclerosis ms inflammatory demyelinating cns disease common neurological immunemediated disorder due progressive format affects patientsnull quality life qol significantly study aimed evaluate epidemiologic parameters ms asia oceania continentsmethodsa comprehensive literature search october 1st 2020 performed pubmed scopus web science retrieve original populationbased studies ms epidemiology asian oceanian countries published january 1st 1985 october 1st 2020 designed search strategy repeated country relevant referenced articles added database randomeffect model used combine epidemiological estimates subgroup analysis also performed continent region country possible metaregression analysis done evaluate effects human developmental index hdi latitude study period epidemiologic parametersresultsa total 3 109 publications found 89 articles met eligibility criteria included data extraction articles provided data prevalence incidence mean age disease onset 18 countries asia oceania including iran turkey cyprus kuwait saudi arabia qatar uae jordan israel india malaysia china hong kong taiwan republic korea japan australia new zealand pooled total prevalence incidence mean age onset asia oceania 3789 100000 95 ci 3565 40142 240 100000 95 ci 222 258 2821 95 ci 2755 2888 respectively ms prevalence incidence female gender 687 100000 442 100000 respectively infinitely higher male gender 2452 100000 206 100000 respectively subgroup analysis showed ms much prevalent australia west asia among studied area metaregression showed total incidence decreased increase hdi total prevalence asia increased increasing latitude gradients also study period positive effect total prevalence incidence asia oceaniaconclusionms prevalence incidence increased recent decades study highlights need studies elucidate msnulls geographical temporal variationsnull exact etiologies,1.0
stable gastric pentadecapeptide bpc 157 wound healing front pharmacol 2021 jun 29 12627533 doi 103389 fphar2021627533 ecollection 2021abstractsignificance antiulcer peptide stable gastric pentadecapeptide bpc 157 previously employed ulcerative colitis multiple sclerosis trials reported toxicity ld1 achieved reviewed focusing particular skin wound therapy incisional excisional wound deep burns diabetic ulcers alkali burns may generalized tissues healing recent advances bpc 157 practical applicability given alone dose range equipotent routes application regardless injury tested critical issues simultaneously curing cutaneous tissue wounds colocutaneous gastrocutaneous esophagocutaneous duodenocutaneous vesicovaginal rectovaginal rats potency bpc 157 evident healing wounds accomplished resolution vessel constriction primary platelet plug fibrin mesh acts stabilize platelet plug resolution clot thereby bpc 157 effective wound healing much like effective counteracting bleeding disorders produced amputation anticoagulants application likewise bpc 157 may prevent attenuate eliminate thus counteract arterial venous thrombosis confronted obstructed vessels circumvention occlusion may particular action bpc 157 ischemia reperfusion future directions bpc 157 rapidly increases various genes expression rat excision skin wound define healing tissues gastrointestinal tract tendon ligament muscle bone nerve spinal cord cornea maintained transparency blood vessels seen bpc 157 therapypmid34267654 pmcpmc8275860 doi103389 fphar2021627533,0.0
metaconsent secondary use health data within learning health system qualitative study publics perspective background advent learning healthcare systems lhss raises important implementation challenge concerning request manage consent support secondary use data learning cycles particularly research activities current consent models quebec established context lhss mind support agility transparency required obtain consent involved especially citizens therefore new approach consent needed previous work identified metaconsent model promising alternative fulfill requirements lhss particularly largescale deployments elicited publics attitude toward metaconsent model evaluate model understood citizens deemed acceptable prepare possible implementation quebecmethodseight focus groups total 63 members general public various backgrounds conducted quebec canada 2019 explicit attention given literacy levels language spoken home rural vs urban settings assessed attitudes concerns facilitators regarding key components metaconsent model predefined categories personalized consent requests dynamic webbased infrastructure record metaconsent default settings analyse discussions thematic content analysis performed using qualitative softwareresultsour findings showed participants supportive new approach consent promotes transparency offers autonomy management health data key facilitators identified considered implementation metaconsent model quebec lhss information transparency awareness campaigns development educational tools collaboration frontline healthcare professionals default settings deemed acceptable society well close partnerships recognized trusted institutionsconclusionsthis qualitative study reveals openness sample quebec population regarding metaconsent model secondary use health data research first exploratory study conducted public important step guiding decisionmakers next phases implementing various strategies support access use health data quebec,0.0
autonomic dysreflexia associated cervical spinal cord gliofibroma case report background autonomic dysreflexia ad abnormal reflex autonomic nervous system normally observed patients spinal cord injury sixth thoracic vertebra ad causes various symptoms including paroxysmal hypertension due stimulus report case recurrent ad associated cervical spinal cord tumorcase presentationthe patient 57yearold man magnetic resonance imaging revealed intramedullary lesion c2 c6 high th12 levels course treatment sudden loss consciousness occurred together abnormal paroxysmal hypertension marked facial sweating left upward conjugate gaze deviation ankylosis upper lower extremities mydriasis seizures repeatedly occurred symptoms disappearing approximately 30 min ad associated cervical spinal cord tumor diagnosed histological examination tumor biopsy confirmed diagnosis gliofibroma radiotherapy performed targeting entire brain spinal cord patient died approximately 3 months treatment startedconclusionsad rarely associated spinal cord tumor first case associated cervical spinal cord gliofibroma ad important recognize since immediate appropriate response required,0.0
healthrelated quality life patients different diseases measured eq5d5l systematic review front public health 2021 jun 29 9675523 doi 103389 fpubh2021675523 ecollection 2021abstractbackground eq5d5l generic preferencebased questionnaire developed euroqol group measure healthrelated quality life hrqol 2005 since development increasingly applied populations various diseases found good reliability sensitivity study aimed summarize health utility elicited eq5d5l patients different diseases crosssectional studies worldwide methods web science medline embase cochrane library searched january 1 2012 october 31 2019 crosssectional studies reporting utility values measured eq5d5l patients specific disease eligible language limited english reference lists retrieved studies manually searched identify studies met inclusion criteria methodological quality assessed agency health research quality ahrq checklist addition metaanalyses performed utility values specific disease reported three studies results total 9 400 records identified 98 studies met inclusion criteria included studies 50 different diseases 98 085 patients analyzed thirtyfive studies involving seven different diseases included metaanalyses health utility ranged 031 099 diabetes mellitus metaanalysis randomeffect model rem 083 95 ci 077090 fixedeffect model fem 093 95 ci 093093 062 090 neoplasms rem 075 95 ci 068082 fem 080 95 ci 078081 056 085 cardiovascular disease rem 077 95 ci 075079 fem 076 95 ci 075076 031 078 multiple sclerosis rem 056 95 ci 047066 fem 067 95 ci 066068 068 079 chronic obstructive pulmonary disease rem 075 95 ci 071080 fem 076 95 ci 075077 065 090 hiv infection rem 084 95 ci 080088 fem 081 95 ci 080082 037 089 chronic kidney disease rem 070 95 ci 048092 fem 076 95 ci 074078 conclusions eq5d5l one widely used preferencebased measures hrqol patients different diseases worldwide variation utility values disease influenced characteristics patients living environment eq5d5l value set systematic review registration https wwwcrdyorkacuk prospero identifier crd42020158694pmid34268287 pmcpmc8275935 doi103389 fpubh2021675523,0.0
averting multiple sclerosis longterm societal healthcare costs value treatment vot project abstractbackground purposethe recent report valueoftreatment vot project highlights need early diagnosisintervention integrated seamless care underpinning timely care pathways access best treatments votmultiplesclerosis ms economic case study analysis aimed estimate effectiveness costeffectiveness early treatment reducing ms risk factors eg smoking vitamin d insufficiency methodsa series decision analytical modellings developed applied estimate costeffectiveness 1 reducing conversion clinicallyisolatedsyndrome cis clinicallydefinitems cdms 2 smoking cessation increase 25 hydroxyvitamin d 25 oh d serum level 1 2 considered socioeconomic impact averted ms disability progression costs reported societal healthcare provider perspectives pending data across nations euros effectiveness expressed qualityadjustedlifeyears qalys gains long term 25 30 40 50years short oneyear timelines considered 1 2 respectivelyresultsearly treatment costeffective health care provider costeffective costsaving society across timehorizons nations smoking cessation increase 25 oh d ms patients costeffective costsaving across nationsconclusionsto best knowledge work provides first economic evidence base appropriate public health interventions reduce ms burden europe,0.0
proposal novel palliative care scale analysis suffering amyotrophic lateral sclerosis rinsho shinkeigaku 2021 may 20 doi 105692 clinicalneurolcn001571 online ahead printabstractobjective proposed novel palliative care scale amyotrophic lateral sclerosis palliative care scale alspcs patients als analyzed suffering reported patientsmethods thirtyone patients participated study alspcs 15 items evaluate physical psychological suffering patients scored subjective suffering scale 05 item study analyzed 13 15 itemsresults mean scores obtained patients follows dyspnea 25 pain 24 restlessness 24 thirst 30 burning sensation 20 choking 20 nausea 04 constipation 15 insomnia 25 anxiety 35 loneliness 24 irritation 21 communication difficulty 23 multiple correlation analysis using spearmans rank correlation coefficient showed significant correlations dyspnea restlessness thirst burning sensation anxiety restlessness dyspnea thirst loneliness irritation anxiety dyspnea thirst loneliness p 00038 bonferronis correction principal component analysis every item showed positive loading value first principal component dyspnea restlessness thirst anxiety loneliness irritation loading values 07 thus symptoms might main features als patients total scores alspcs score showed significant association postassessment survival periodconclusion study using alspcs showed subjective suffering als patients variable strongly correlated appropriate comprehensive assessment physical psychological affliction alspcs potentially useful verifying effectiveness palliative care endoflife stage als patients futurepmid34011812 doi105692 clinicalneurolcn001571,0.0
determinants macular ganglion cellinner plexiform layer thickness normal chinese adults background demographic systemic ocular factors may impact macular ganglion cellinner plexiform layer gcipl thickness measurements study aimed investigate influences multiple potential determinants macular gcipl thickness normal chinese adultsmethodsthis retrospective study conducted 225 normal eyes 225 healthy chinese adults gcipl thickness obtained using cirrus highdefinition optical coherence tomography oct age gender laterality spherical equivalent se refractive error intraocular pressure iop axial length al central cornea thickness cct circumpapillary retinal nerve fibre layer prnfl thickness oct signal strength recorded respective effect gcipl thickness parameters evaluatedresultsthe mean sd average minimum superotemporal superior superonasal inferonasal inferior inferotemporal gcipl thickness 8456 536 8132 558 8308 537 8570 595 8715 626 8507 611 8246 576 8388 559 m respectively determinants thinner gcipl thickness older age p 00010117 effects enhanced age 40 years thinner prnfl p 0001 weaker signal strength p 0001 significant difference found males females p 00690842 right eyes left eyes p 01600875 except superonasal gcipl thickness p 0001 significant correlation gcipl thickness se iop cct al p 01350968 conclusionsindividual determinants associated thinner gcipl thickness older age particularly 40 years age thinner prnfl weaker oct signal strength relevant comprehensively understanding normative data differentiating normal aging abnormalities,0.0
evaluation remote assessments multiple sclerosis inhome setting abstractbackgroundthere urgent clinical need reliable remote monitoring methods multiple sclerosis ms evaluated use remotely patientrecorded timed 25foot walk rt25fw ninehole peg test r9hpt methodsseventyone people ms completed previouslyvalidated online edss webedss r9hpt 108 completed webedss rt25fwresultsthere mildmoderate positive correlation webedss rt25fw significant correlation webedss r9hpt distributions rt25fw r9hpt times positively skewedconclusionsour results provide pilot evidence remote monitoring ms potentially valid requires refinement widescale implementation median edss 45 edss range 0 80 least patients ambulatory difficulty able complete assessments,0.0
lingo1 regulates wnt5a signaling neural stem progenitor cell differentiation modulating mir15b3p levels background manipulation neural stem progenitor cells nspcs critical successful treatment spinal cord injury sci nspc transplantation since differentiation neurons oligodendrocytes can inhibited factors present inflamed myelin study examined effects lingo1 spinal cordderived nspc spnspc differentiation underlying mechanisms action functional recovery mice transplantation manipulated cellsmethodsspnspcs harvested female adult c57 bl6 mice sci induced nyu impactor cells infected lentiviral vectors containing lingo1 shrna sequence scrambled control transplanted sci mice tuj1 gfappositive cells assessed immunofluorescence staining wnt5a pjnk jnk catenin expression determined western blot rtqpcr mirnas sequenced detect changes mirna expression motor function evaluated 035 days postsurgery means basso mouse scale bms rotarod performance testresultswe discovered lingo1 shrna increased neuronal differentiation spnspcs decreasing astrocyte differentiation effects accompanied elevated wnt5a protein expression unexpectedly changes wnt5a mrna levels mirnasequence analysis demonstrated mir15b3p downstream mediator lingo1 suppressed wnt5a expression transplantation lingo1 shrnatreated spnspcs sci mice promoted neural differentiation wound compaction motor function recoveryconclusionslingo1 shrna promotes neural differentiation spnspcs wnt5a expression probably downregulating mir15b3p transplantation lingo1 shrnatreated nspcs promotes recovery motor function sci highlighting potential target sci treatment,1.0
performance highly cited multiple sclerosis publications science citation index expanded bibliometric analysis abstractbackgroundthe present study aims identify analyze characteristics highly cited publications multiple sclerosis science citation index expandedmethodsdocuments 100 citations considered highly cited documents highly cited publications analyzed distribution document types languages publication years web science categories journals well publication performance countries institutions authors six five publication indicators applied compare publications countries institutes respectively highly cited authors analyzed yindexresultsin general articles spent 12 years highly cited articles usa dominated production six publication indicators harvard university active research multiple sclerosis university california los angeles usa shows independent research m filippi recognized productive author articles corresponding authorconclusionthe findings may interest multiple sclerosis researchers policymakers around world,0.0
smek1 deficiency exacerbates experimental autoimmune encephalomyelitis activating proinflammatory microglia suppressing ido1ahr pathway background experimental autoimmune encephalomyelitis eae animal disease model multiple sclerosis ms involves immune system central nervous system cns however unclear genetic predispositions promote neuroinflammation ms eae investigated partial lossoffunction suppressor mek1 smek1 regulatory subunit protein phosphatase 4 facilitates onset ms eaemethodsc57bl 6 mice immunized myelin oligodendrocyte glycoprotein 3555 mog3555 establish eae model clinical signs recorded pathogenesis investigated immunization cns tissues analyzed immunostaining quantitative polymerase chain reaction qpcr western blot analysis enzymelinked immunosorbent assay elisa singlecell analysis carried cortices hippocampus splenic lymph node cells evaluated flow cytometry qpcr western blot analysisresultshere showed partial smek1 deficiency caused severe symptoms eae model controls activating myeloid cells smek1 required maintaining immunosuppressive function modulating indoleamine 2 3dioxygenase ido1 aryl hydrocarbon receptor ahr pathway singlecell sequencing vitro study showed smek1deficient microglia macrophages preactivated steady state mog3555 immunization microglia macrophages underwent hyperactivation produced increased il1 smek1 + mice peak stage moreover dysfunction ido1ahr pathway resulted reduction interferon ifn enhanced antigen presentation ability inhibition antiinflammatory processes smek1 + eae miceconclusionsthe present study suggests protective role smek1 autoimmune demyelination pathogenesis via immune suppression inflammation regulation immune system central nervous system findings provide instructive basis roles smek1 eae broaden understanding genetic factors involved pathogenesis autoimmune demyelination,1.0
use margin stability quantify stability pathologic gait qualitative systematic review background margin stability mos widely used objective measure dynamic stability gait increasingly researchers using mos assess stability pathological populations gauge stability capabilities coping strategies objective marker outcome response treatment disease progression objectives describe types pathological gait assessed using mos examine methods used assess mos examine way mos data presented interpretedmethodsa systematic review conducted accordance preferred reporting items systematic reviews metaanalyses guidelines prisma following databases web science pubmed ucl library explore cochrane library scopus articles measured mos pathologically affected adult human population whilst walking straight line extracted data collected per prospectively defined list included population type method data analysis model building walking tasks undertaken interpretation mosresultsthirtyone studies included final review 15 different clinical populations studied commonly poststroke unilateral transtibial amputee populations participants assessed gait laboratory using motion capture technology whilst 2 studies used instrumented shoes variety centre mass base support mos definitions calculations describedconclusionsthis first systematic review assess use mos first consider clinical application findings suggest mos potential helpful objective measurement variety clinically affected populations unfortunately methodology interpretation varies hinders subsequent study comparisons lack baseline results large studies mean direct comparison studies difficult strong conclusions hard make work biomechanics community develop reporting guidelines mos calculation methodology commitment larger baseline studies pathology welcomed,0.0
thymosin 4 reverses phenotypic polarization glial cells cognitive impairment via negative regulation nfb signaling axis app ps1 mice background thymosin 4 t4 abundant member thymosins plays important role control actin polymerization eukaryotic cells effects multiple organs diseases widely investigated safety profile established animals humans currently little known influence alzheimers disease ad possible mechanisms thus aimed evaluate effects mechanisms t4 glial polarization cognitive performance app ps1 transgenic micemethodsbehavior tests conducted assess learning memory anxiety depression app ps1 mice thioflavin s staining nissl staining immunohistochemistry immunofluorescence elisa qrtpcr immunoblotting performed explore accumulation phenotypic polarization glial cells neuronal loss function tlr4 nfb axis app ps1 miceresultswe demonstrated t4 protein level elevated app ps1 mice overexpression t4 alone alleviated adlike phenotypes app ps1 mice showed less brain accumulation insulindegrading enzyme ide reversed phenotypic polarization microglia astrocyte healthy state improved neuronal function cognitive behavior performance accidentally displayed antidepressantlike effect besides t4 downregulate tlr4 myd88 nfb p65 p52dependent inflammatory pathways app ps1 mice combination drug tlr4 antagonist tak242 nfb p65 inhibitor pdtc exerted effectsconclusionsthese results suggest t4 may exert function regulating classical noncanonical nfb signaling restoring function potential therapeutic target ad,0.0
association multiple sclerosis osteoarthritis germany retrospective cohort study 8 600 patients germany mult scler j exp transl clin 2021 jun 28 7 2 20552173211022784 doi 101177 20552173211022784 ecollection 2021 aprjunabstractobjectives goal retrospective cohort study investigate multiple sclerosisosteoarthritis relationship adults followed general practices germanymethods patients aged 1870 years diagnosed first time multiple sclerosis one 1 193 general practices germany 2005 2018 index date included retrospective cohort study patients without multiple sclerosis matched 11 multiple sclerosis sex age index year general practice obesity injuries types arthritis index date randomly selected visit date association multiple sclerosis 10year incidence osteoarthritis analyzed using cox regression modelsresults 4 300 patients multiple sclerosis 4 300 patients without multiple sclerosis included study proportion women 693 mean sd age 436 126 years significant association multiple sclerosis incident osteoarthritis overall sample hr 095 95 ci 083109 well sex age subgroupsconclusions based findings multiple sclerosis significantly associated osteoarthritis studies longitudinal nature warranted corroborate invalidate resultspmid34262785 pmcpmc8243106 doi101177 20552173211022784,0.0
role plantderived natural compounds experimental autoimmune encephalomyelitis review treatment potential development strategy front pharmacol 2021 jun 28 12639651 doi 103389 fphar2021639651 ecollection 2021abstractmultiple sclerosis ms autoimmune disease central nervous system mainly mediated pathological tcells experimental autoimmune encephalomyelitis eae wellknown animal model ms used study underlying mechanism offers theoretical basis developing novel therapy ms good therapeutic effects observed administration natural compounds derivatives treatments eae however severe lag research development drug mechanisms related ms review examines natural products potential effectively treat ms relevant data consulted order elucidate regulated mechanisms acting upon eae flavonoids glycosides triterpenoids derived natural products addition novel technologies network pharmacology molecular docking highthroughput screening gradually applied natural product development information provided herein can help improve targeting timeliness determining specific mechanisms involved natural medicine treatment lay foundation studypmid34262447 pmcpmc8273381 doi103389 fphar2021639651,0.0
working child demyelinating optic neuritis striking balance oman j ophthalmol 2021 jun 28 14 2 7477 doi 104103 ojoojo_105_21 ecollection 2021 mayaugabstractpediatric optic neuritis pon one commonest causes acute vision loss children although might often postinfectious postvaccination recent understanding available evidence suggest can first manifestation neuroinflammatory syndrome multiple sclerosis neuromyelitis optica spectrum disorder acute disseminated encephalomyelitis myelin oligodendrocyte glycoprotein associated optic neuritis therefore neuroimaging serological testing cerebrospinal fluid analysis testing various systemic autoimmune conditions become part workup however can exhaustive expensive especially countries limited access health insurance many recent studies suggest neuroimaging clinical features can provide clues underlying etiology however serological tests can provide confirmatory evidence therefore minireview propose balanced approach evaluation pon based available literature emanating last decadepmid34345139 pmcpmc8300277 doi104103 ojoojo_105_21,1.0
multidimensional analysis detection informative features human brain white matter plos comput biol 2021 jun 28 17 6 e1009136 doi 101371 journalpcbi1009136 online ahead printabstractthe white matter contains longrange connections different brain regions organization connections holds important implications brain function health disease tractometry uses diffusionweighted magnetic resonance imaging dmri quantify tissue properties along trajectories connections statistical inference tractometry usually either averages quantities along length fiber bundle computes regression models separately point along every one bundles approaches limited sensitivity former case statistical power latter developed method based sparse group lasso sgl takes account tissue properties along bundles selects informative features enforcing global bundlelevel sparsity demonstrate performance method two settings classification setting patients amyotrophic lateral sclerosis als accurately distinguished matched controls furthermore sgl identifies corticospinal tract important classification correctly finding parts white matter known affected disease ii regression setting sgl accurately predicts brain age case weights distributed throughout white matter indicating many different regions white matter change lifespan thus sgl leverages multivariate relationships diffusion properties multiple bundles make accurate phenotypic predictions simultaneously discovering relevant features white matterpmid34181648 doi101371 journalpcbi1009136,0.0
standardizing fatigue measurement multiple sclerosis validity responsiveness score interpretation promis sf v10 fatigue ms 8a abstractbackgroundfatigue one common single disabling symptom multiple sclerosis ms however lack consensus appropriate fatigue measures clinical practice research based upon rigorously validated generalizable publicly available instruments objective research generate additional evidence regarding validity applicability promis sf v10 fatigue ms 8a including content validity reliability construct validity responsiveness well assess minimal important difference mid estimates score interpretation tool aide meaningful individual level score interpretationmethodsa mixedmethods sequential design followed cognitive debriefing cd interviews n29 performed ms patients assess relevance comprehensiveness promis fatigue ms 8a scores evaluate psychometric properties promis fatigue ms 8a two observational studies conducted crosssectional study two us ms centers n296 96week longitudinal study uk ms register cohort n384 main outcomes measures estimates knowngroups validity convergence validity reliability responsiveness guide interpreting promis fatigue ms 8a tscores anchorbased mid estimatesresultsthe cd interviews confirmed comprehensiveness relevance promis fatigue ms 8a assessing ms fatigue cronbachnulls alpha 09 intraclass correlation coefficient 09 testretest scores 57 days followup supported strong internal consistency testretest reliability hypothesized differences found across patient groups patient reported fatigue related concepts analysis variance anova p 0001 promis fatigue ms 8a scores sensitive bidirectional changes fatigue ghs fatigue global question physical health promis ghs gph 52week followup score changes 344 points proposed mid criteria minimal improvement worsening fatigueconclusionthis research extends evidence supporting content validity robust psychometric performance promis fatigue ms 8a across us uk ms populations importantly data supporting measurenulls integration clinical practice research including meaningful score interpretation now available,0.0
plasma peptides alzheimers disease background practical strategy discover proteins specific alzheimers dementia ad may compare plasma peptides proteins patients dementia normal controls patients neurological conditions like multiple sclerosis diseases aim proof principle method discover proteins peptides plasma show greater observation frequency precursor intensity ad endogenous tryptic peptides alzheimers compared normals multiple sclerosis ovarian cancer breast cancer female normal sepsis icu control heart attack along institutionmatched controls normal samples collected directly onto icemethodsendogenous tryptic peptides extracted blinded individual ad control edta plasma samples step gradient acetonitrile random independent sampling lcesims ms set robust sensitive linear quadrupole ion traps ms ms spectra fit fully tryptic peptides within proteins identified using xtandem algorithm observation frequency identified proteins counted using sequest algorithm proteins apparently increased observation frequency ad versus ad control revealed graphically subsequently tested chi square analysis proteins specific ad plasma chi square fdr correction analyzed string algorithm average protein peptide log10 precursor intensity compared across disease control treatments anova r statistical systemresultspeptides phosphopeptides common plasma proteins complement c2 c7 c1qbp among others showed increased observation frequency chi square precursor intensity ad cellular gene symbols large chi square values 2 25 p 0001 tryptic peptides included kif12 disc1 or8b12 zc3h12a tnf tbc1d8b galnt3 eme2 cd1b bag1 cpsf2 mmp15 dnajc2 phactr4 or8b3 gck exosc7 hmga1 nt5c3a among others similarly increased frequency tryptic phosphopeptides observed mok smim19 nxnl1 slc24a2 nbla10317 ahrr c10orf90 maea srsf8 tbata tnik ube2g1 pde4c pcgf2 kir3dp1 tjp2 cpne8 ngf amongst others string analysis showed increase cytoplasmic proteins proteins associated alternate splicing exocytosis luminal proteins proteins involved regulation cell cycle mitochondrial functions metabolism apoptosis increases mean precursor intensity peptides common plasma proteins disc1 exosc5 ube2g1 smim19 nxnl1 pano eif4g1 kir3dp1 med25 mgrn1 or8b3 mgc24039 polr1a sytl4 rnf111 ireb2 ankmy2 sgkl slc25a5 chmp3 among others associated ad tryptic peptides highly conserved cterminus disc1 within sequence mpgggpqgapaaaggggvshragsrdclppaacfr arqcgldsr showed higher frequency highest intensity ad compared disease controlsconclusionproteins apparently expressed brain directly related alzheimers including nerve growth factor nfg sphingomyelin phosphodiesterase disrupted schizophrenia 1 disc1 cell death regulator retinitis pigmentosa nxnl1 governs loss nerve cells retina cell death regulator zc3h12a showed much higher observation frequency ad plasma vs matched control striking agreement proteins known mutated disregulated brains ad patients proteins observed plasma ad patients endogenous peptides including nbn bag1 nox1 pdcd5 sgk3 ube2g1 smpd3 neuronal proteins associated synapse function ksytl4 vti1b brain specific proteins tbata,1.0
designing selfperception cognitive questionnaire italian multiple sclerosis patients sclerosi multipla autovalutazione cognitiva smac preliminary exploratory pilot study front neurol 2021 jun 28 12668933 doi 103389 fneur2021668933 ecollection 2021abstractbackground although cognition multiple sclerosis ms assessed means several neuropsychological tests tools exist investigate patients perspectives cognitive functioning objective develop new questionnaire aimed exploring patients selfperception respect cognition italian ms patients methods total 120 relapsingremitting ms rrms patients 120 matched healthy controls hc completed 25item questionnaire called sclerosi multipla autovalutazione cognitiva smac symbol digit modalities test sdmt deliskaplan executive function system sorting test dkefs st beck depression inventory bdiii fatigue scale fss also administered patients results significantly higher smac scores displayed rrms patients compared hc 301 169 vs 234 104 p 0003 smac inversely correlated sdmt r 031 p 0001 dkefs st fsc r 021 p 0017 dkefs st fsd r 022 p 0015 dkefs st sr r 019 p 0035 positively correlated fss r 042 p 0001 bdiii r 059 p 0001 cronbachs alpha coefficient questionnaire 094 conclusion preliminary findings suggest smac promising patientreported outcome included ms neuropsychological evaluation thus warrants tested developedpmid34262521 pmcpmc8273489 doi103389 fneur2021668933,0.0
quality life predictors adults tuberous sclerosis complex tsc multicentre cohort study germany background tuberous sclerosis complex tsc monogenetic multisystemic disease characterised formation benign tumours can affect almost organs caused pathogenic variations tsc1 tsc2 multicentre study germany investigated influence sociodemographic clinical therapeutic factors quality life qol among individuals tscmethodswe assessed sociodemographic clinical characteristics qol among adults tsc throughout germany using validated threemonth retrospective questionnaire examined predictors healthrelated qol hrqol using multiple linear regression analysis compared qol among patients tsc qol among patients chronic neurological disordersresultswe enrolled 121 adults tsc mean age 310 105 years range 1861 years 455 n 55 women unemployment higher grade disability higher number organ manifestations presence neuropsychiatric manifestations active epilepsy higher burden therapyrelated adverse events associated worse qol measured two qol instruments euroqol5 dimensions eq5d quality life epilepsy patients qolie31 neuropsychiatric structural nervous system manifestations number affected organs therapyrelated adverse events also associated higher depression measured neurological disorders depression inventory epilepsy nddie multiple regression analysis severe therapyrelated adverse events large effect p 0001 active epilepsy large effect p 0001 neuropsychiatric manifestations medium effect p 0003 independently associated worse hrqol explaining 65 variance p 0001 hrqol among patients active tscassociated epilepsy worse among patients drugrefractory mesial temporal lobe epilepsy p 0001 generic qol among patients three tsc organ manifestations similar patients severe migraine uncontrolled asthmaconclusionsactive epilepsy neuropsychiatric manifestations anxiety depression therapyrelated adverse events important independent predictors worse quality life among adults tsc generic quality life tsc several manifestations similar uncontrolled severe chronic diseases significantly negatively correlates tsc severitytrial registrationdrks drks00016045 registered 01 march 2019,0.0
type 2 sclerotic modic change affect fusion result patients undergoing plif pedicle screw instrumentation retrospective study background bony fusion rate significantly lower patients type 3 modic change patients normal endplates known whether relevant differences fusion efficiency among patients type 2 sclerotic modic change nonsclerotic modic change modic changemethodsa retrospective study contained 196 lumbar segments 123 subjects undergoing posterior lumbar interbody fusion plif pedicle screw instrumentation psi assess effect type 2 sclerotic modic change fusion efficiency endplates allocated groups b c according modic changes group endplates type 2 modic change endplate sclerosis group b type 2 modic change without endplate sclerosis group c neither modic change endplate sclerosis presence modic change determined magnetic resonance imaging mri endplate sclerosis type 2 modic change detected computed tomography ct operation collected ct data 3 months 24 months operation patients assess bony fusionresultsincidences bony fusion 588 group 950 group b 943 group c bony fusion rate significantly lower group either group b c significant difference groups b c thus endplates type 2 sclerotic modic change lower fusion rate patients undergoing plif psiconclusiontype 2 sclerotic modic change important factor affects solid bony fusion patients undergoing plif psi ct may help diagnose endplate sclerosis patients type 2 change inform choice best site spinal fusion,0.0
enhanced liver fibrosis test maintains diagnostic prognostic performance alcoholrelated liver disease cohort study background alcohol main cause chronic liver disease enhanced liver fibrosis elf test serological biomarker fibrosis staging chronic liver disease however utility alcoholrelated liver disease warrants validation assessed diagnostic prognostic performance elf alcoholrelated liver disease methodsobservational cohort study assessing paired elf histology 786 tertiary care patients chronic liver disease due alcohol n 81 nonalcohol aetiologies n 705 prognostic data available 64 alcohol patients median 64 years multiple elf cutoffs assessed determine diagnostic utility moderate fibrosis cirrhosis survival data assessed determine ability elf predict liver related events allcause mortalityresultself identified cirrhosis moderate fibrosis alcoholrelated liver disease independently aminotransferase levels areas receiver operating characteristic curves 0895 95 ci 08230968 0923 95 ci 08660981 respectively noninferior nonalcohol aetiologies overall performance elf assessed using obuchowski method alcohol 0934 95 ci 09080960 nonalcohol 0907 95 ci 08950919 using elf 98 exclude 105 diagnose cirrhosis 877 alcohol cases avoided biopsy sensitivity 91 specificity 85 oneunit increase elf associated 26 95 ci 155431 p 0001 fold greater odds cirrhosis baseline 20fold greater risk liver related event within 6 years 95 ci 139299 p 0001 conclusionself accurately stages liver fibrosis independently transaminase elevations marker inflammation superior prognostic performance biopsy alcoholrelated liver disease,0.0
global prevalence familial multiple sclerosis updated systematic review metaanalysis background considering many recent studies reported prevalence familial multiple sclerosis fms performed updated metaanalysis worldwide prevalence fms addition recent publicationsmethodsa search pubmed scopus isi web science google scholar undertaken 20 december 2020 inclusion criteria based cocopop approach condition context population metaanalysis qualified studies conducted comprehensive metaanalysis ver 2 softwareresultsthe pooled prevalence ms relatives 16 179 fms cases estimated 118 95 ci 10713 based randomeffects model pooled mean age disease onset adult probands calculated 287 years 95 ci 272 302 regarding 13 studies reported data fms pediatrics n 877 adults n 6636 fms prevalence pediatrics adults 155 95 ci 138174 108 95 ci 81142 respectively prevalence fms affected males n 5243 females n 11 503 calculated 137 95 ci 101182 154 95 ci 103224 respectively odds ratio male female fms cases statistically significant 09 95 ci 0612 p 055 subgroup analysis demonstrated significant difference prevalence fms geographical areas p 0007 metaregression model indicated prevalence fms lower higher latitude higher ms prevalence p 0001 contrast metaregression based prevalence day statistically significant p 029 conclusionsthe prevalence fms higher pediatric group adults distinct geographical areas diminishes increment ms prevalence latitude also symptoms initiate relatively younger ages fms cases interestingly analysis unveiled fms prevalent men women risk ms development relatives higher affected proband male,0.0
post transplantation cyclophosphamide improves outcome autologous hematopoietic stem cell transplantation animal model multiple sclerosis arch immunol ther exp warsz 2021 jun 28 69 1 17 doi 101007 s00005021006194abstractexperimental allergic encephalomyelitis eae animal model multiple sclerosis ms autologous hematopoietic stem cell transplantation ahsct recently recognized standard treatment ms aim experiment investigate effect ahsct addition lowdose posttransplantation cyclophosphamide cy eae rats low dose posttransplantation cy used haploidentical hsct reduce risk graft versus host disease hypothesized bring additional benefit autologous hsct autoimmune diseases rats evoked eae treated high dose 125 mg kg cy followed ahsct high dose 125 mg kg cy followed ahsct followed low dose 20 mg kg cy twotime scheduleswith therapy applied presymptomatic symptomatic phase disease ahsct ahsct posttransplantation cy accordance time schedules reduce intensity inflammatory response cns comparison nontreated eae rats reduction clinical symptoms present ahsct treatment protocols however significantly stronger posttransplantation cy given symptomatic phase disease ahsct addition post hsct low dose cy improved results ahsct reducing intensity inflammation cns also significantly reducing clinical symptoms treated animals compared ahsct alone provide experimental rationale addition posttransplantation cy may improve outcome hsct mspmid34181099 doi101007 s00005021006194,0.0
biomechanical analysis unpowered hip flexion orthosis individuals without multiple sclerosis background gait impairment common complication multiple sclerosis ms gait limitations limited hip flexion foot drop knee hyperextension often require external devices like crutches canes orthoses effects mobilityassistive technologies mats prescribed people ms well understood current devices cater specific needs individuals address passive unilateral hip flexionassisting orthosis hfo developed uses resistance bands spanning hip joint redirect energy gait cycle purpose study investigate shortterm effects hfo gait mechanics muscle activation people without ms hypothesized 1 hip flexion increase limb wearing device 2 muscle activity increase hip extensors decrease hip flexors plantar flexorsmethodsfive healthy subjects five subjects ms walked minutelong sessions device using three different levels band stiffness analyzed peak hip flexion extension angles lower limb joint work muscle activity eight muscles lower limbs trunk singlesubjects analysis used due intersubject variabilityresultsfor subjects ms hfo caused increase peak hip flexion angle decrease peak hip extension angle confirming first hypothesis healthy subjects showed less pronounced kinematic changes using device power generated hip increased subjects using hfo second hypothesis confirmed muscle activity showed inconsistent results however several subjects demonstrated increased hip extensor trunk muscle activity hfoconclusionsthis exploratory study showed hfo welltolerated healthy subjects subjects ms promoted normative kinematics hip ms future studies longer exposure hfo personalized assistance parameters needed understand efficacy hfo mobility assistance rehabilitation people ms,0.0
association stat4 gene polymorphism type 2 diabetes risk chinese han population background evidence genetic epidemiology indicates type 2 diabetes t2d strong genetic basis activated stat4 inflammatory effect stat4 important mediator inflammation diabetes study aimed study association stat4 single nucleotide polymorphisms snps t2d susceptibility chinese han populationmethodswe conducted casecontrol study among 500 t2d patients 501 healthy individuals 5 candidate stat4 snps successfully genotyped association snps t2d susceptibility different genetic models evaluated logistic regression analysis snpsnp interaction analyzed completed multifactor dimensionality reduction mdr finally evaluated differences clinical characteristics different genotypes onefactor analysis varianceresultsthe overall results showed stat4 rs3821236 associated increasing t2d risk allele 123 p 0020 homozygous 151 p 0025 dominant 136 p 0029 additive models 123 p 0020 results stratified analysis showed rs3821236 rs11893432 rs11889341 risk factors t2d among participants 60 years old rs11893432 associated increased t2d risk among female participants also potential association rs3821236 t2d nephropathy risk stat4 rs11893432 rs7574865 rs897200 significantly associated lysophosphatidic acid cystatin c thyroxine t4 respectivelyconclusionthe genetic polymorphisms stat4 potentially associated t2d susceptibility chinese population particular rs3821236 significantly associated t2d risk overall several subgroup analyses study may provide new ideas t2d individualized diagnosis protection,0.0
antiphospholipid antibodies anticoagulant therapy capillaroscopic findings background antiphospholipid syndrome aps systemic autoimmune disease characterized specific vascular obstetric manifestations antiphospholipid antibodies apl positivity microvascular damage course aps apl carrier patients without symptoms poorly investigatedobjectivesthis study aims compare nailfold videocapillaroscopy nvc microvascular parameters aps patients nonsymptomatic apl carriers investigate possible correlations different apl subtypesmethodsnvc performed standard evaluations 18 aps patients mean age 50 138 years 24 apl carriers without symptoms mean age 464 164 years 18 control patients ctr mean age 74 125 years taking oral anticoagulants nonimmunological indications ie cardiovascular accidents patients investigated presence dilated capillaries giant capillaries microhemorrhages capillary loss nonspecific specific abnormalities ie branched bushy capillaries sign neoangiogenesis nvc every alteration also classified according semiquantitative score lupus anticoagulant anticardiolipin antibodies antibeta2 glycoprotein antibodies tested patientresultsaps patients showed nvc increased frequency microhemorrhages p 0039 particularly comblike pattern parallel hemorrhages p 0002 apl carriers note significant differences concerning isolated number microhemorrhages aps ctr group p 0314 comblike hemorrhages significantly frequent aps group p 0034 significant correlation found apl subtypes nvc parametersconclusionsaps patients showed significantly greater number nonspecific nvc abnormalities apl carriers particularly comblike nvc pattern oral anticoagulants may represent confounding factor isolated microhemorrhages correlation found apl subtypes nvc parameters investigations needed better characterize microvascular endothelium damage induced apl,0.0
beneficial effects nano formulation pomegranate seed oil granagard cognitive function multiple sclerosis patients abstractbackgroundthough often neglected cognitive impairment common feature multiple sclerosis 4370 patients none novel ms treatment seems substantially affect restore cognitive disability ms granagard granalix bio technologies ltd food supplement shown prevent neuronal death several animal models neurological diseases capsules granagard comprise selfemulsion nano formulation pomegranate seed oil pso oil contains 8090 punicic acid pa one strongest natural antioxidants animal experiments administration granagard results conjugation linoleic acid cla main metabolite pa wellknown neuroprotective agentaimsto investigate whether granagard administration effect cognitive state ms patientsmethodsthis single center randomized double blind clinical trial started may 2018 study included 30 ms patients half groupa given granagard first three months placebo pills containing soybean oil additional three months patients groupb received placebo first three months granagard following three months granagard administrated addition immunomodulatory mstreatments subsequently patients received granagard additional six months patients required visit neurologist baseline inclusion visit 1 3 months treatmentinitiation cycle trial visits 2 3 follow visits clinical cognitive examinations performed including expanded disability status scale edss multiple sclerosis functional composite msfc 25ft walking test 9 peg hole test pasat cognitive tests included brief international cognitive assessment multiple sclerosis bicams battery 1 symbol digit modalities test sdmt 2 california verbal learning test second edition cvltii 3 brief visuospatial memory test revised bvmtr cognitive outcomes normalized healthy population expressed zscores depended age gender education short quality life fatigue questionnaires sf12 mfis5 also provided participantsresultsno serious adverse effects related product observed study period patients receiving granagard reported nullpositivenull effect adl using product significant differences clinical parameters disability edss scores treatment groups trend beneficial effect granagard verbal testing first 3month period treatment z score cvltii significantly increased 0891 1415 p0012 wilcoxon rank test 3months group patients treated granagard compared baseline similar statistically significant trend seen also bvmtr testing 3 monthsperiod whereas change sdmt overall average zscore three cognitive functions significantly improved three months granagard treatment 00077 3 months vs 0462 baseline p0034 wilcoxon rank test 3months period significant changes placebotreated group patients receiving granagard initial 3 months value z score cvltii remained high z1415 also following three months received placebo suggesting longer lasting effect least 3 months discontinuation drugconclusionthis first study granagard brain targeted nanoformulation pso tested humans results small pilot controlled trial provide indications granagard administration ms patients might improve stabilize cognitive disability larger studies longer duration needed confirm initial observations,1.0
descriptive correlational study evaluate three measures assessing upper extremity function individuals multiple sclerosis mult scler int 2021 jun 26 20215588335 doi 101155 2021 5588335 ecollection 2021abstractbackground activities daily living quality life qol hindered upper extremity ue impairments experienced individuals multiple sclerosis ims ninehole peg test 9hpt frequently used measure ue function however measure peoples ability perform routine tasks daily life may useful ims pick pegs utilized 9hpt therefore evaluated three measures explore comprehensive assessment ue function upper extremity function scale uefs action research arm test arat 9hpt objectives quantitatively assess relationship measures ue function understand measures correlate qol calculated ms quality life54 msqol54 determine differences measures based employment statusmethods 112 79 female ims prospectively recruited descriptive correlational study inclusion criteria follows confirmed diagnosis ms clinically isolated syndrome age 18 years ability selfconsent statistical analyses including spearmans correlation coefficient r s kruskalwallis tests performed using spssresults moderate correlation r s 051 p 0001 found arat 9hpt scores impaired hand likewise moderate correlation found uefs physical health composite scores phcss msqol54 r s 059 p 0001 finally performances arat 9hpt uefs differed employed individuals longterm disability p 0007 p 0001 p 0001 conclusion uefs moderately correlated qol measure considering uesf patientreported outcome used complement routinely captured measures assessing ue function study warranted determine measure combination measures sensitive changes ue function timepmid34258067 pmcpmc8257389 doi101155 2021 5588335,0.0
b cells neuroinflammation new perspectives mechanistic insights cells 2021 jun 26 10 7 1605 doi 103390 cells10071605abstractin recent years role b cells neurological disorders substantially expanded perspectives mechanisms neuroinflammation success b celldepleting therapies patients cns diseases neuromyelitis optica multiple sclerosis highlighted importance neuroimmune crosstalk inflammatory processes b cells essential adaptive immune system antibody production also major contributors pro antiinflammatory cytokine responses number inflammatory diseases b cells can contribute neurological diseases peripheral immune mechanisms including production cytokines antibodies cns mechanisms following compartmentalization emerging evidence suggests aberrant pro antiinflammatory b cell populations contribute neurological processes including glial activation implicated pathogenesis several neurodegenerative diseases review summarize recent findings b cell involvement neuroinflammatory diseases discuss evidence support pathogenic immunomodulatory functions b cells neurological disorders highlighting importance b celldirected therapiespmid34206848 doi103390 cells10071605,0.0
comparison intestinal microbiome italian patients multiple sclerosis household relatives life basel 2021 jun 26 11 7 620 doi 103390 life11070620abstractmultiple sclerosis ms chronic immunemediated disease central nervous system caused combination genetic environmental factors recent years role ms pathogenesis assigned gut microbiota however different signatures gut dysbiosis shown depend environmental factors like diet lifestyle study compared gut microbiome ms patients household healthy relatives sharing lifestyle environmental factors faecal metagenomic dna extracted v3v4 regions conserved bacterial 16s ribosomal rna gene amplified sequenced overall bacterial communities similar specific families differed healthy ms subjects observed increase ruminococcaceae christensenellaceae desulfovibrionaceae clostridiales family xiii ms patients bacteroidaceae tannerellaceae veillonellaceae burkholderiaceae abundant healthy controls addition principle coordinate analysis showed gut microbiome ms patients formed cluster less diverse household relatives gut microbiota ms patients edss 457 formed distinct cluster respect controls overall study consistent hypothesis ms patients gut microbial dysbiosis evidenced importance environmental factors shaping gut microbiomepmid34206853 doi103390 life11070620,0.0
opinions beliefs knowledge people multiple sclerosis covid19 pandemic vaccine abstractbackgroundconsidering potential covid19 impact pwms health importance vaccination population decided assess pwmsnull beliefs knowledge covid19 pandemic b acceptance towards covid19 vaccination c pwmsnull opinions general vaccinationmethodsobservational study based crosssectional 1020th september 2020 online survey conducted cohort pwmsnull followed two portuguese hospitals survey included measures characterize sample questionnaire designed assess topics defined studyresults270 respondents completed full survey response rate 582 pwms greatest concern pandemic aggravation ms especially patients older 50 years old almost 40 patients older 50 felt pandemic negatively affected ms related medical assistance patients believed recover covid19 infection half responders feared ms aggravation got covid19 pronounced patients progressive ms 12 participants want vaccinated almost 40 unsure regarding vaccines general almost third participants feared side effects ms related complicationsconclusionhaving knowledge pwmsnull opinions covid19 pandemic impact vaccination useful better address issues fears expectations towards vaccination must discussed pwms,0.0
beyond lesion site minocycline augments inflammation anxietylike behavior following sci rats action gut microbiota background minocycline clinically available synthetic tetracycline derivative antiinflammatory antibiotic properties majority studies show minocycline can reduce tissue damage improve functional recovery following central nervous system injuries mainly attributed drugs direct antiinflammatory antioxidative neuroprotective properties surprisingly consequences minocyclines antibiotic ie antibacterial effects gut microbiota systemic immune response spinal cord injury largely ignored despite links changes mental health immune suppressionmethodshere sought determine minocyclines effect spinal cord injuryinduced changes microbiotaimmune axis using cervical contusion injury female lewis rats investigated group received minocycline following spinal cord injury immediately injury 7 days untreated spinal cord injury group untreated uninjured group uninjured group received minocycline plasma levels cytokines chemokines fecal microbiota composition using 16s rrna sequencing monitored 4 weeks following spinal cord injury measures microbiotaimmune axis additionally motor recovery anxietylike behavior assessed throughout study microglial activation analyzed immediately rostral caudal lesion epicenterresultswe found minocycline profound acute effect microbiota diversity composition paralleled subsequent normalization spinal cord injuryinduced suppression cytokines chemokines importantly gut dysbiosis following spinal cord injury linked development anxietylike behavior also decreased minocycline furthermore although minocycline attenuated spinal cord injuryinduced microglial activation affect lesion size promote measurable motor recoveryconclusionwe show minocyclines microbiota effects precede longterm effects systemic cytokines chemokines following spinal cord injury results provide exciting new target minocycline therapeutic central nervous system diseases injuries,1.0
olig2 regulates lncrnas expression oligodendrocyte lineage formation background oligodendrocytes responsible axon ensheathment critical central nervous system cns development function diseases olig2 important transcription factor tf acts oligodendrocyte development performs distinct functions different stages previous studies shown lncrnas long noncoding rnas 200 bp important functions oligodendrocyte development roles systematically characterized regulation yet clearresultswe performed integrated study genomewide olig2 binding epigenetic modification status coding noncoding genes three stages oligodendrocyte differentiation vivo neural stem cells nscs oligodendrocyte progenitor cells opcs newly formed oligodendrocytes nfos found 613 lncrnas olig2 binding sites expressed least one cell type can potentially activated repressed olig2 fortyeight increased expression oligodendrocyte lineage cells predicting lncrna functions using guiltbyassociation approach revealed functions 48 lncrnas enriched oligodendrocyte development differentiation additionally bivalent genes known play essential roles embryonic stem cell differentiation identified bivalent genes nscs opcs nfos found bivalent genes bound olig2 dynamically regulated oligodendrocyte development importantly unveiled previously unknown mechanism addition transcriptional regulation via dna binding olig2 selfregulate 3 utr mrnaconclusionsour studies revealed missing links mechanisms regulating oligodendrocyte development transcriptional level transcription results research improved understanding fundamental cell fate decisions oligodendrocyte lineage formation can enable insights demyelination diseases regenerative medicine,1.0
chances challenges longterm data repository multiple sclerosis 20th birthday german ms registry sci rep 2021 jun 25 11 1 13340 doi 101038 s4159802192722xabstractin 2001 german multiple sclerosis society facing lack data founded german ms registry gmsr longterm data repository ms healthcare research establishment network participating neurological centres different healthcare sectors across germany gmsr provides observational realworld data longterm disease progression sociodemographic factors treatment healthcare status people ms paper aims illustrate framework gmsr structure design data quality processes well collaborations gmsr presented registrys dataset status results discussed 08 january 2021 187 centres different healthcare sectors participate gmsr following infrastructure dataset specification upgrades 2014 196 000 visits recorded relating 33 000 persons ms pwms gmsr enables monitoring pwms germany supports scientific research projects collaborates national international ms data repositories initiatives recent pharmacovigilance extension aligns ema recommendations helps ensure early detection therapyrelated safety signalspmid34172792 doi101038 s4159802192722x,0.0
psychological wellbeing people multiple sclerosis association illness perception selfesteem abstractbackground illness perception selfesteem found improve adjustment disease many chronic conditions however far little known role illnessappraisal selfappraisal factors psychological wellbeing people multiple sclerosis ms thus aimed assess association illness perception selfesteem psychological wellbeing people ms controlling sociodemographic variables clinical variables sleeprelated problemsmethods general health questionnaire28 brief illness perception questionnaire rosenberg scale selfesteem expanded disability status scale pittsburgh sleep quality index multidimensional fatigue inventory used multiple linear regressions mediation analyses utilized analyse dataresults positive illness perception p0001 selfesteem p005 significantly associated psychological wellbeing ms low income p005 sleeprelated problems p0001 significantly associated lower level psychological wellbeing people ms positive illness perception selfesteem able diminish association low income p005 poor sleep quality p001 fatigue p005 low level psychological wellbeing selfesteem also mediated association illness perception psychological wellbeingdiscussion people ms may benefit psychological support aimed promoting selfesteem diminishing negative illness perception,0.0
new targeted compoundsbiosynthesis phytocannabinoids sheng wu gong cheng xue bao 2021 jun 25 37 6 19681985 doi 1013345 jcjb200453abstractphytocannabinoids bioactive terpenoids exclusive cannabis sativa l main pharmacologically active phytocannabinoids 9tetrahydrocannabinol cannabidiol target endogenous cannabinoid receptors 9tetrahydrocannabinol cannabidiol extensive therapeutic potential due participation many physiological pathological processes human body activating endocannabinoid system present 9tetrahydrocannabinol cannabidiol analogues combination preparations used treat epilepsy vomiting patients cancer chemotherapy spasticity multiple sclerosis relieve neuropathic pain pain patients advanced cancer exploration application value 9tetrahydrocannabinol cannabidiol well increasing demand standardization pharmaceutical preparations imminent achieve largescale production 9tetrahydrocannabinol cannabidiol pharmaceutical industry article pharmacological research progress phytocannabinoids recent years biosynthetic pathways phytocannabinoids mechanism key enzymes well various product development strategies cannabinoids pharmaceutical industry reviewed exploring potential synthetic biology alternative strategy source phytocannabinoids will provide theoretical basis research development microbial engineering cannabinoids synthesis promote largescale production medicinal cannabinoidspmid34227288 doi1013345 jcjb200453,0.0
sjgrens syndrome nervous system injury combined withpulmonary osseous cryptococcosis case report background sjgrens syndrome common autoimmune disease can involve nervous system rarely central peripheral longterm use highdose corticosteroids immunosuppressants main risk factors cryptococcus infection patients sjgrens syndrome pulmonary infection common multiple bone infections rarecase presentationa 46yearold chinese woman 2year history sjgrens syndrome presented hospital numbness limbs shortness breath weakness blood immunochemistry showed antinuclear antibody 1640 antisjgrens syndromea antibodies anticentromere antibodies strongly positive cranial magnetic resonance imaging revealed multiple demyelinating lesions white matter bilateral cerebral hemispheres electromyography indicated serious peripheral nerve injury especially lower limbs computed tomography scan lumbar vertebral displayed multiple highdensity shadows corresponding vertebrae magnetic resonance imaging showed abnormal low signal intensity t1 t2 sequences positron emission tomographycomputed tomography showed multiple lesions high 18ffluorodeoxyglucose uptake lung vertebral bodies lung bone biopsies suggested cryptococcus infection diagnosis sjgrens syndrome nervous system injury combined pulmonary osseous cryptococcosis took reduced dose prednisone 10 mg day terminated mycophenolate mofetil began take immunoglobulin 04 g kg day intravenously 5 days fluconazole 400 mg day 6 months within 3 weeks chest radiography showed marked improvement 3 months later pulmonary lesions disappeared computed tomography scanconclusionsthis case exhibits extremely rare condition neural involvement sjgrens syndrome combined pulmonary osseous cryptococcosis report also highlights crucial role detailed clinical examination serologic markers biopsy avoiding misdiagnosis currently guideline situation case controlled disease successfully antifungal drugs adequate gamma globulin followed appropriate dose corticosteroids,1.0
early predictors conversion secondary progressive multiple sclerosis abstractbackground conducted study estimated time conversion relapsingremitting ms rrms spms early predictor factorsmethods retrospective study demographic clinical imaging data ms patients diagnosis extracted cox proportional hazards model used assess association various baseline characteristics conversion spms also assessed association brtween escalation early intensive therapy approaches transition progressive phaseresults 1903 patients rrms baseline 293 154 patients progressed spms followup estimated number patients converted spms 10 10years 50 20years 93 30years multivariate cox regression analysis older age onset hr 1067 95ci 10481085 p0001 smoking hr 2120 95ci 12033736 p0009 higher edss onset hr 1199 95ci 11091295 p0001 motor dysfunction hr 2470 95ci 16053800 p0001 cerebellar dysfunction hr 3096 95ci 18405211 p0001 presence lesions spinal cord hr 0573 95ci 02970989 p0042 increased risk conversion rrms spms significant difference escalation eit groups risk transition progressive phase weighted hr1438 95 ci 0963 2147 p0076 foundconclusion data support previous observations smoking modifiable risk factor secondary progressive ms confirms spinal cord involvement age severe disease onset prognostic factors converting secondary progressive ms,1.0
altered expression ion channels white matter lesions progressive multiple sclerosis know function front cell neurosci 2021 jun 25 15685703 doi 103389 fncel2021685703 ecollection 2021abstractdespite significant advances understanding pathophysiology multiple sclerosis ms knowledge contribution individual ion channels axonal impairment remyelination failure progressive ms remains incomplete ion channel families play fundamental role maintaining white matter wm integrity regulating wm activities axons interstitial neurons glia vascular cells recently transcriptomic studies considerably increased insight gene expression changes occur diverse wm lesions gene expression fingerprint specific wm cells associated secondary progressive ms review ion channel genes encoding k+ ca2+ na+ cl channels ryanodine receptors trp channels others significantly uniquely dysregulated active chronic active inactive remyelinating wm lesions normalappearing wm secondary progressive ms brain based recently published bulk singlenuclei rnasequencing datasets discuss current state knowledge corresponding ion channels implication ms brain experimental models ms comprehensive review suggests intense upregulation voltagegated na+ channel genes wm lesions ongoing tissue damage may reflect imbalance na+ homeostasis observed progressive ms brain upregulation large number voltagegated k+ channel genes may linked protective response limit neuronal excitability addition altered chloride homeostasis revealed significant downregulation voltagegated cl channels ms lesions may contribute altered inhibitory neurotransmission increased excitabilitypmid34276310 pmcpmc8282214 doi103389 fncel2021685703,1.0
validation two kinetic assays quantification endotoxin human serum front neurol 2021 jun 25 12691683 doi 103389 fneur2021691683 ecollection 2021abstractbackground emerging evidence role microbiome neurological diseases endotoxin component gramnegative bacteria thought one possible signals gut microbiota immune system previous studies explored blood levels endotoxin using endpoint chromogenic assay methods validated compared analytical performance two kinetic assays quantification endotoxin serum 1 limulus amebocyte lysate lal kineticqcl assay 2 turbidimetric lal pyrogent5000 assay used bestperforming validated assay measure endotoxin level 20 patients multiple sclerosis ms eight healthy controls results pyrogent5000 qcl assay achieved similar performance regard spike recovery linear dilution however pyrogent5000 better signal noise calibrator curve using pyrogent5000 assay found serum samples ms patients healthy controls similar level endotoxin hence find evidence support penetration endotoxin blood ms patients findings exclude role endotoxin mediating signals gut microbiota ms patients directly gutblood barrier numerous antigenpresenting cells actively sensing metabolites bacterial productspmid34248828 pmcpmc8266997 doi103389 fneur2021691683,0.0
key role ccr2ccl2 axis disease modification mouse model tauopathy background decades dementia characterized accumulation waste brain lowgrade inflammation years emerging studies highlighted involvement immune system neurodegenerative disease emergence severity numerous studies animal models amyloidosis demonstrated beneficial role monocytederived macrophages mitigating disease though less known regarding tauopathy boosting immune system animal models amyloidosis tauopathy resulted improved cognitive performance reduction pathological manifestations however full understanding chain events involved starting activation immune system leading disease mitigation remained elusive hypothesized brainimmune communication pathway needed activated combat tauopathy involves monocyte mobilization via cc chemokine receptor 2 ccr2 ccl2 axis additional immune cells cd4+ t cells including foxp3+ regulatory cd4+ t cellsmethodswe used dmhtau transgenic mice mouse model tauopathy applied approach boosts immune system via blocking inhibitory programmed cell death protein1 pd1 pdl1 pathway manipulation previously shown alleviate disease symptoms pathology anticcr2 monoclonal antibody ccr2 used block ccr2 axis protocol partially eliminates monocytes circulation time antipdl1 antibody pdl1 injection critical period recruitment brain following treatmentresultsperformance dmhtau mice shortterm working memory tasks revealed beneficial effect pdl1 assessed 1 month single injection abrogated following blockade ccr2 accompanied loss beneficial effect disease pathology assessed measurement cortical aggregated human tau load using homogeneous time resolved fluorescencebased immunoassay evaluation hippocampal neuronal survival using multiparametric flow cytometry cytometry time flight demonstrated accumulation foxp3+ regulatory cd4+ t cells brain 12 days following treatment absent subsequent ccr2 blockade addition measurement hippocampal levels tcell chemoattractant cxc motif chemokine ligand 12 cxcl12 inflammatory cytokines revealed pdl1 treatment reduced expression blocking ccr2 reversed effectconclusionsthe ccr2 ccl2 axis required modify pathology using pdl1 blockade mouse model tauopathy modification involves addition monocytes accumulation foxp3+ regulatory cd4+ t cells brain tcell chemoattractant cxcl12,0.0
clinical relevance depressed kynurenine pathway episodic migraine patients potential prognostic markers peripheral plasma interictal period background altered glutamatergic neurotransmission neuropeptide levels play central role migraine pathomechanism previously confirmed kynurenic acid endogenous glutamatergic antagonist able decrease expression pituitary adenylate cyclaseactivating polypeptide 138 neuropeptide known migraineinducing properties hence aim reveal role peripheral kynurenine pathway kp episodic migraineurs focused complete tryptophan trp catabolism comprises serotonin melatonin routes addition kynurenine metabolites investigated relationship metabolic alterations clinical characteristics migraine patientsmethodsfemale migraine patients aged 25 50 years n 50 healthy control subjects n 34 participated study blood samples collected cubital veins subjects interictal ictal periods migraineurs n 47 12 respectively 12 metabolites trp pathway determined neurochemical measurements uhplcms ms resultsplasma concentrations trp metabolites remarkably decreased interictal period migraineurs compared healthy control subjects especially migraine without aura mwoa subgroup trp p 0025 lkynurenine p 0001 kynurenic acid p 0016 anthranilic acid p 0007 picolinic acid p 003 5hydroxyindoleaceticacid p 0025 melatonin p 0023 several metabolites showed tendency elevate ictal phase significant cases anthranilic acid 5hydroxyindoleaceticacid melatonin mwoa patients subgroup higher interictal kynurenic acid levels identified patients whose headache severe related menstruation cycle negative linear correlation detected interictal levels xanthurenic acid melatonin attack frequency positive associations found ictal 3hydroxykynurenine levels beginning attacks just ictal picolinic acid levels last attack ictal samplingconclusionsour results suggest widespread metabolic imbalance migraineurs manifests completely depressed peripheral trp catabolism interictal period might act trigger migraine attack contributing glutamate excess induced neurotoxicity generalised hyperexcitability data can draw attention clinical relevance kp migraine,0.0
lateonset neuromuscular disorders differential diagnosis sarcopenia background sarcopenia agerelated loss muscle mass strength undiagnosed lateonset neuromuscular disorders need considered differential diagnosis sarcopeniaaimbased emblematic case reports current neuromuscular diagnostic guidelines three common lateonset neuromuscular disorders differential diagnostic approach geriatric patients presenting sarcopenic phenotype givenmethodspatients 65 years age sarcopenia amyotrophic lateral sclerosis inclusion body myositis myotonic dystrophy type 2 recruited patients assessed sarcopenia based revised european consensus definition patients neuromuscular diseases diagnosed according revised el escorial criteria european neuromuscular centre criteria phenotypes diagnostic criteria patients summarized including specific histopathological findingsresultsall patients neuromuscular diseases positively screened sarcopenia classified severe sarcopenic means assessment clinical phenotype evolution pattern weakness muscle atrophy combined laboratory finding including electromyography unquestionably distinguish diseasesdiscussionneuromuscular disorders can manifest beyond age 65 years misdiagnosed sarcopenia common diseases inclusion body myositis amyotrophic lateral sclerosis myotonic dystrophy type 2 diagnostic workup neuromuscular diseases ensures correct diagnosis clinical electrophysiological histopathological genetic workupconclusionsin geriatric patients focal asymmetrical muscular weakness atrophy sarcopenia assessment extended patients history disease course furthermore concomitant diseases analysis serum creatine kinase electrophysiological examination selected patients muscle biopsy gene analysis needed rule lateonset neuromuscular disorder,0.0
microwave ablation eustachian tuboplasty preliminary investigation longterm followup abstractobjectivesthis study performed evaluate efficacy microwave ablation mwa eustachian tuboplasty treatment patients retracted tympanic membrane tm due eustachian tube dysfunction etd methodsthis prospective study 20 patients etd middle ear atelectasis underwent mwa eustachian tuboplasty outcomes included ability perform valsalva maneuver audiometry results tympanometry results etd questionnaire etdq7 score tm statusresultseighteen patients 18 ears included study statistically clinically significant improvements mean etdq7 score 6 months postoperatively change mean score 167 36 p 0001 30 months postoperatively change mean score 189 29 p 0001 type tympanogram obtained 278 patients 5 18 6 months postoperatively 777 30 months postoperatively valsalva maneuver possible 722 patients 6 months postoperatively 889 patients 30 months postoperatively addition ears 13 patients 722 showed normal tympanograms tm 30 months postoperatively interestingly 385 patients 5 13 exhibited complete sclerosis pars tensa none patients experienced severe mwarelated complications followupconclusionsmwa eustachian tuboplasty feasible alternative conventional tuboplasty can improve subjective objective outcomes patients etd 30 months following treatment addition study showed extent sclerotic plaque increased time whereas extents atrophy tensa retraction decreased following tuboplasty patientsgraphical abstract,0.0
sarscov2 infection multiple sclerosis results spanish neurology society registry neurol neuroimmunol neuroinflamm 2021 jun 24 8 5 e1024 doi 101212 nxi0000000000001024 print 2021 julabstractobjective understand covid19 characteristics people multiple sclerosis ms identify highrisk individuals due immunocompromised state resulting use diseasemodifying treatmentsmethods retrospective multicenter registry patients ms suspected confirmed covid19 diagnosis available disease course mild ambulatory severe hospitalization critical intensive care unit death cases analyzed associations ms characteristics covid19 course identifying risk factors fatal outcomeresults 326 patients analyzed 120 cases confirmed realtime pcr 34 serologic test 205 suspected sixtynine patients 213 developed severe infection 10 3 critical 7 21 died ambulatory patients higher relapsing ms forms treated injectables oral firstline agents whereas severe cases observed patients pulsed immunosuppressors critical cases among patients therapy severe critical infections likely affect older males comorbidities progressive ms forms longer disease course higher disability fifteen 33 patients treated rituximab hospitalized four deceased patients progressive ms 5 receiving ms therapy 2 treated natalizumab rituximab multivariate analysis showed age 109 95 ci 104117 independent risk factor fatal outcomeconclusions study demonstrated presumed critical role ms therapy course covid19 evidenced people ms advanced age disease progressive course disabled higher probability severe even fatal diseasepmid34168057 doi101212 nxi0000000000001024,0.0
evaluation peripheral immune activation amyotrophic lateral sclerosis front neurol 2021 jun 24 12628710 doi 103389 fneur2021628710 ecollection 2021abstractaccumulating evidence revealed immunity plays important role amyotrophic lateral sclerosis als progression however results regarding serum levels immunoglobulin complement inconsistent patients als although immune dysfunctions also reported patients neurodegenerative diseases studies explored whether immune dysfunction als similar neurodegenerative diseases therefore performed study address gaps present study serum levels immunoglobulin complement measured 245 patients als 65 patients multiple system atrophy msa 60 patients parkinsons disease pd 82 healthy controls hcs multiple comparisons revealed significant differences existed patients als neurodegenerative diseases immunoglobulin complement levels metaanalysis based data cohort eight published articles performed evaluate serum immunoglobulin complement patients als hcs pooled results showed patients als higher c4 levels hcs addition found igg levels lower earlyonset als patients lateonset als patients hcs correlations age onset als igg iga levels significant positive conclusion data supplement existing literature understanding role peripheral immunity alspmid34248812 pmcpmc8264193 doi103389 fneur2021628710,0.0
multiple sclerosis pseudotumoral demyelinating lesions female adolescent presenting optic neuritis bmj case rep 2021 jun 24 14 6 e244837 doi 101136 bcr2021244837no abstractpmid34167968 doi101136 bcr2021244837,1.0
multiple sclerosis projection tehran iran using bayesian structural time series background prevalence multiple sclerosis ms increasing worldwide highest prevalence ratio among asian countries reported iran study aims estimate increase ms occurrence three decades tehran forecast future condition disease using time series approaches next ten yearsmethodsthe crosssectional study conducted 1999 2019 based records ms cases iranian ms society imss registry system prevalence estimated using population data presented statistical centre iran bayesian structural time series bsts model want predict prevalence familial sporadic ms next ten years resultsamong 22 421 cases ms 16 831 751 female 5589 249 male female male ratio 301 number familial ms cases 2982 133 subjects female gender less responsible higher rate ms familial definition beta 0020 comparison sporadic cases beta 0034 forecasting bsts revealed increase ms prevalence next ten years prevalence rate total familial sporadic ms respectively begins 18950 1839419514 2569 24972645 16374 1590616857 2020 ends 22084 1714826692 3079 24163715 18933 1469723019 2029conclusionsaccording findings ms prevalence increased three decades will increase next ten years tehran province one regions highest ms prevalence asia results present study indicated females higher risk ms males sporadic familial ms,0.0
exploring use health wellbeing measures pregnancy first year following birth women living preexisting longterm conditions qualitative interviews women healthcare professionals background one way care pregnant postpartum women living longterm health conditions ltcs may improved adoption standardised measures provide evidence health outcomes wellbeing womans perspectiveaimthe study explores views pregnant postpartum women living ltcs healthcare professionals better understand potential value using standardised health wellbeing measures within patient populationmethodsqualitative semistructured telephone interviews conducted explore perceived value using measures pregnant postpartum women living ltcs within maternity services participants asked provide feedback three exemplar measures long term conditions questionnaire wellbeing pregnancy questionnaire euroqol eq5d5l instrument thematic analysis used analysis transcriptsresultseleven women 11 healthcare professionals took part semistructured interviews analysis identified five themes relevant use measures within maternity services 1 improving care 2 assessing outcomes 3 interpretation application data 4 engagement challenges implementation 5 women healthcare professionals alignmentconclusionsdespite varying prior experience expressing questions implementation respondents cautiously positive use standardised health wellbeing measures use offers opportunity affected women healthcare professionals caring collectively identify assess important areas unmet needs improve outcomes incorporating perspectives women ltcs will help bring awareness elements women centred care health services may seek address,0.0
low continuation antipsychotic therapy parkinson disease intolerance ineffectiveness inertia background antipsychotics used parkinson disease pd treat psychosis mood behavioral disturbances commonly used antipsychotics differ substantially potential worsen motor symptoms dopaminergic receptor blockade recent realworld data use continuation antipsychotic therapy pd lacking objectives study 1 examine continuation overall initial antipsychotic therapy individuals pd 2 determine whether continuation varies drug dopamine receptor blocking activitymethodswe conducted retrospective cohort study using us commercially insured individuals optum 20012019 adults aged 40 years older pd initiating antipsychotic therapy continuous insurance coverage least 6 months following drug initiation included exposure pimavanserin quetiapine clozapine aripiprazole risperidone olanzapine identified based pharmacy claims sixmonth continuation overall initial antipsychotic therapy estimated time complete discontinuation switching different antipsychotic cox proportional hazards models evaluated factors associated discontinuationresultsoverall 386 3566 pd patients sample discontinued antipsychotic therapy first prescription 614 continued overall treatment within 6 months initiation clozapine use rare include statistical analyses overall therapy discontinuation likely initiated medications known dopaminereceptor blocking activity adjusted hazard ratios 176 95 confidence interval 140220 quetiapine 215 161286 aripiprazole 212 166272 risperidone 207 160267 olanzapine compared serotonin receptorspecific pimavanserin initial antipsychotic therapy discontinuation also associated greater dopaminereceptor blocking activity medication use adjusted hazard ratios 157 128194 188 143246 200 159252 203 160258 quetiapine aripiprazole risperidone olanzapine respectively compared pimavanserin similar results observed sensitivity analysesconclusionsover onethird individuals pd discontinued antipsychotic therapy especially initial drug greater dopaminereceptor blocking activity understanding drivers antipsychotic discontinuation including ineffectiveness potentially inappropriate use clinician inertia patient adherence adverse effects needed inform clinical management psychosis pd appropriate antipsychotic use population,0.0
optimized protocol subcutaneous implantation encapsulated cells device evaluation biocompatibility front bioeng biotechnol 2021 jun 24 9620967 doi 103389 fbioe2021620967 ecollection 2021abstractimproving drug delivery system critical treat central nervous system disorders studied innovative approach based implantation wirelesspowered cellbased device mice device coupling biologic material electronics first kind advantage technology ability control secretion therapeutic molecule switch classical permanent delivery activation demand diseases relapsingremitting phases multiple sclerosis activation selectively achieved relapsing phases however safety tolerance biomaterials surgical procedure clinical device needs verified therefore development tools assess biocompatibility system animal models essential step present development new therapeutic approach challenges encountered different steps development cell loading chamber surgery protocol subcutaneous implantation device tools used evaluate cell viability biocompatibility devicepmid34249877 pmcpmc8264370 doi103389 fbioe2021620967,0.0
healthcare needs expectations utilization experienced treatment effects patients hereditary spastic paraplegia webbased survey netherlands background aimed identify healthcare needs expectations utilization experienced treatment effects population dutch patients hereditary spastic paraplegia hsp methodswe distributed online questionnaire among 194 adult persons hsp netherlands 166 returned fully completed version applying predefined exclusion criteria 109 questionnaires persons pure hsp analysedresultshealthcare needs expectations primarily focused relief muscle stiffness reduction balance gait impairments 6580 many participants also expressed needs regarding relief nonmotor symptoms eg pain fatigue emotional problems impaired sleep selfcare capacity participation problems 60 remarkably despite frequent needs relatively participants 33 expected able improve additional domains rehabilitation physicians physiotherapists frequently consulted neurologists occupational therapists respectively physiotherapy often proposed nonpharmacological intervention 85 followed orthopedic footwear 55 splints 28 approximately one third participants never offered pharmacological spasmolytic treatment spasmolytic oral drugs injections intrathecal baclofen given 41 26 5 participants respectively independent type pharmacological intervention 3546 participants experienced decreased spastiticy improved general fitness experienced effects differed per type interventionconclusionsbased webbased survey netherlands seems ample room improvement meet attune healthcare needs expectations people hsp concerning motor nonmotor symptoms functional limitations addition provision adequate information nonpharmacological pharmacological interventions seems insufficient many patients allow shared decision making conclusions warrant proactive attitude healthcare providers well interdisciplinary approach substantial proportion hsp population also involving professionals primary occupational psychosocial orientation,0.0
sphingosine 1phosphate receptor modulators multiple sclerosis conditions summarythe sphingosine 1phosphate s1p signalling pathways important diverse functions s1p receptors s1prs proposed therapeutic target various diseases due involvement regulation lymphocyte trafficking brain cardiac function vascular permeability vascular bronchial tone s1pr modulators first developed prevent rejection immune system following renal transplantation currently approved indication multiple sclerosis primary mechanism action s1pr modulators multiple sclerosis binding s1pr subtype 1 lymphocytes resulting internalisation receptor loss responsiveness s1p gradient drives lymphocyte egress lymph nodes reduction circulating lymphocytes presumably limits inflammatory cell migration cns four s1pr modulators fingolimod siponimod ozanimod ponesimod regulatory approval multiple sclerosis preclinical evidence ongoing completed clinical trials support development s1pr modulators therapeutic indications,0.0
comprehensive database integrated analysis omics data autoimmune diseases background autoimmune diseases heterogeneous pathologies difficult diagnosis therapeutic options last decade several omics studies provided significant insights molecular mechanisms diseases nevertheless data different cohorts pathologies stored independently public repositories unified resource imperative assist researchers field resultshere present autoimmune diseases explorer https adexgenyoes database integrates 82 curated transcriptomics methylation studies covering 5609 samples common autoimmune diseases database provides easytouse environment advanced data analysis statistical methods exploring omics datasets including metaanalysis differential expression pathway analysis conclusionsthis first omics database focused autoimmune diseases resource incorporates homogeneously processed data facilitate integrative analyses among studies,0.0
macrolide inspired macrocycles modulators il17a il17ra interaction j med chem 2021 jun 8 doi 101021 acsjmedchem1c00327 online ahead printabstractinterleukin 17 il17 cytokines promote inflammatory pathophysiology many autoimmune diseases including psoriasis multiple sclerosis rheumatoid arthritis inflammatory bowel disease broad involvement il17 various autoimmune diseases makes ideal target drug discovery psoriasis chronic inflammatory disease characterized numerous defective components immune system significantly higher levels il17a noticed lesions psoriatic patients compared nonlesion parts therefore paper focused macrolide inspired macrocycles potential il17a il17ra modulators covers molecular design synthesis vitro profiling macrocycles designed diversify enrich chemical space different ring sizes variety threedimensional shapes inhibitors nm range identified targetbased phenotypic assays vitro adme well vivo pk properties reportedpmid34100601 doi101021 acsjmedchem1c00327,0.0
continence issues individuals living multiple sclerosis br j nurs 2021 jun 24 30 12 700704 doi 1012968 bjon20213012700no abstractpmid34170735 doi1012968 bjon20213012700,0.0
forearm muscle mitochondrial capacity resting oxygen uptake relationship symptomatic fatigue persons multiple sclerosis mult scler j exp transl clin 2021 jun 24 7 2 20552173211028875 doi 101177 20552173211028875 ecollection 2021 aprjunabstractbackground mitochondrial dysfunction implicated pathogenesis multiple sclerosis ms whether mitochondrial alterations function ambulatory dysfunction nonambulatory systemic nature unclearobjective compare oxidative capacity rest muscle oxygen consumption mvo2 upper limb persons multiple sclerosis pwms control group con whereby upper limb comparatively independent ambulation deconditioningmethods near infrared spectroscopy used measure oxidative capacity wrist flexors pwms n 16 con n 13 oxidative capacity indicated time constant tc mvo2 recovery following brief wrist flexion contractions measurements included wellbeing depression symptomatic fatigue disability handgrip strength cognition functional endurance analysis ttests pearson correlations p 005 data mean sd results tc mvo2 recovery slower pwms ms 47 14 sec con 36 11 sec p 003 significant correlations found oxidative capacity measures rest mvo2 different groups correlated symptomatic fatigue r 0694 p 0003 strength 0585 p 0017 pwmsconclusion oxidative capacity lower wrist flexors pwms possibly indicating systemic component disease within pwms rest mvo2 associated symptomatic fatiguepmid34262786 pmcpmc8246512 doi101177 20552173211028875,0.0
cortical phase rim lesions 7 t mri markers multiple sclerosis disease progression brain commun 2021 jun 24 3 3 fcab134 doi 101093 braincomms fcab134 ecollection 2021abstractin multiple sclerosis individual lesiontype patterns magnetic resonance imaging might valuable predicting clinical outcome monitoring treatment effects neuropathological imaging studies consistently show cortical lesions contribute disease progression presence chronic active white matter lesions harbouring paramagnetic rim susceptibilityweighted magnetic resonance imaging also associated aggressive form multiple sclerosis however still uncertain two types lesions relate one plays greater role disability progression prospective longitudinal study 100 multiple sclerosis patients 74 relapsingremitting 26 secondary progressive used ultrahigh field 7t susceptibility imaging characterize cortical rim lesion presence evolution clinical evaluations obtained mean period 32 years 71 patients 46 followup magnetic resonance imaging baseline cortical rim lesions identified 96 63 patients respectively rim lesion prevalence similar across disease stages patients rim lesions higher cortical overall white matter lesion load subjects without rim lesions p 0018005 altogether cortical lesions increased count volume p 0004 time rim lesions expanded volume p 0023 whilst lacking new rim lesions rimless white matter lesions increased count decreased volume p 0016 used modern machine learning algorithm based extreme gradient boosting techniques assess cumulative power well individual importance cortical rim lesion types predicting disease stage disability progression alongside traditional imaging markers influential imaging features discriminated multiple sclerosis stages area curvestandard deviation 082 008 included expected normalized white matter thalamic volume white matter lesion volume also leukocortical lesion volume subarachnoid cerebrospinal fluid leukocortical lesion volumes along rim lesion volume important predictors expanded disability status scale progression area curvestandard deviation 069 012 taken together results indicate cortical lesions extremely frequent multiple sclerosis rim lesion development occurs subset patients however persist time relate disease progression combined assessment needed improve ability identifying multiple sclerosis patients risk progressing diseasepmid34704024 pmcpmc8361394 doi101093 braincomms fcab134,0.0
surface amp deaminase 2 novel regulator modifying extracellular adenine nucleotide metabolism abstractadenine nucleotides represent crucial immunomodulators extracellular environment ectonucleotidases cd39 cd73 responsible sequential catabolism atp adenosine via amp thus promoting antiinflammatory milieu induced adenosine halo ampd2 intracellularly mediates amp deamination imp thereby enhancing degradation inflammatory atp reducing formation antiinflammatory adenosine show enzyme expressed surface human immune cells predominance may modify inflammatory states altering extracellular milieu surface ampd2 eampd2 expression monocytes verified immunoblot surface biotinylation mass spectrometry immunofluorescence microscopy flow cytometry revealed enhanced monocytic eampd2 expression tlr stimulation pbmcs patients rheumatoid arthritis displayed significantly higher levels eampd2 expression compared healthy controls furthermore product ampd2impexerted antiinflammatory effects levels extracellular adenosine impaired increased eampd2 expression summary study identifies eampd2 novel regulator extracellular atpadenosine balance adding immunomodulatory cd39cd73 system,0.0
stateoftheart review demyelinating diseases indonesia mult scler int 2021 jun 23 20211278503 doi 101155 2021 1278503 ecollection 2021abstractdemyelinating diseases common indonesia previously believed however still challenge country indonesia implement scientific medical advances especially diagnostic process demyelinating diseases achieve best possible outcome groups patients within constraints socially technologically economically logistically achievable review address 4 major classes demyelinating disease multiple sclerosis ms neuromyelitis optica nmo antimogassociated encephalomyelitis mogem acute disseminated encephalomyelitis adem discuss prevalence demographics clinical diagnosis workup imaging features indonesian population well challenges face diagnosis therapeutic approach hope overview will lead better awareness spectrum demyelinating diseases central nervous system indonesiapmid34327021 pmcpmc8277524 doi101155 2021 1278503,1.0
multiple pathways toxicity induced c9orf72 dipeptide repeat aggregates g 4 c 2 rna cellular model elife 2021 jun 23 10e62718 doi 107554 elife62718abstractthe frequent genetic cause amyotrophic lateral sclerosis frontotemporal dementia g4c2 repeat expansion c9orf72 gene expansion gives rise translation aggregating dipeptide repeat dpr proteins including polyga abundant species however gain toxic function effects attributed either dprs pathological g4c2 rna analyzed cellular model relative toxicity dprs rna cytoplasmic polyga aggregates generated absence g4c2 rna interfered nucleocytoplasmic protein transport little effect cell viability contrast nuclear polyga toxic impairing nucleolar protein quality control protein biosynthesis production g4c2 rna strongly reduced viability independent dpr translation caused pronounced inhibition nuclear mrna export protein biogenesis thus toxic effects g4c2 rna predominate cellular model used dprs exert additive effects may contribute pathologypmid34161229 doi107554 elife62718,0.0
cannabidiol use effectiveness realworld evidence canadian medical cannabis clinic background cannabidiol cbd primary component cannabis plant however recent years interest cbd treatments outpaced scientific research regulatory advancement resulting confusing landscape misinformation unsubstantiated health claims within limited results randomized controlled trials lack trust product quality known clinical guidelines dosages realworld evidence rwe countries robust regulatory frameworks may fill critical need patients healthcare professionals despite growing evidence interest realworld data rwd studies yet investigated patients reports cbd impact symptom control common expression pain anxiety depression poor wellbeing objective study assess impact cbdrich treatment symptom burden measured specific symptom assessment scale esasr methodsthis retrospective observational study examined pain anxiety depression symptoms wellbeing 279 participants 18 years old prescribed cbdrich treatment network clinics dedicated medical cannabis quebec canada data collected baseline 3 fup1 6 fup2 month treatment initiation groups formed based symptom severity mild vs moderate severe based changes treatment plan fup1 cbd vs thccbd twoway mixed anovas used assess esasr scores differences groups visitsresultsall average esasr scores decreased baseline fup1 ps 0003 addition delta9tetrahydrocannabinol thc first followup effect symptom changes patients moderate severe symptoms experienced important improvement fup1 ps 0001 whereas scores pain anxiety wellbeing mild symptoms actually increased differences esasr scores fup1 fup2 statistically differentconclusionthis retrospective observational study suggests cbdrich treatment beneficial impact pain anxiety depression symptoms well overall wellbeing patients moderate severe symptoms however observed effect mild symptoms results study contribute address myths misinformation cbd treatment demand investigation,0.0
frequency characteristics falls people living without multiple sclerosis covid19 pandemic crosssectional online survey abstractbackgroundpublic health responses coronavirus disease 2019 covid19 including lockdowns may negatively impact physical mental functioning clinical populations people living multiple sclerosis ms may susceptible physical function deterioration practicing social distancing recent reports suggested 50 people ms pwms decreased leisure physical activity covid19 upwards 30 reported decreased physical fitness levels however impact social distancing adverse healthrelated outcomes falls received much scrutiny therefore explored frequency characteristics falls experienced people living without ms covid19 pandemicmethodstwohundred thirtynine individuals including 106 pwms median age 59 years 133 people living without ms median age 66 years recruited crosssectional study snowball sampling strategy used online recruitment participants completed customized falls questionnaire number falls experienced covid19 recorded fallrelated characteristics timing locations activities undertaken falling consequences well selfreported physical activity also recordedresultsoverall participants reported 232 falls 167 falls person pwms 041 falls person nonms participants people living ms pwms significantly higher frequency falls 585 vs 218 p 0001 recurrent falls 453 vs 98 p 0001 compared nonms participants additionally pwms reported significantly higher proportion inhome falls 839 vs 542 p0004 well higher proportion overall injuries 443 vs 125 p 0001 fractures 57 vs 08 p0048 healthcare utilization 94 vs 16 p0007 compared nonms participants similar proportion pwms 491 nonms participants 522 reported lower physical activity levels covid19conclusionthis crosssectional study revealed pwms remain high risk falls fallrelated outcomes covid19 high number falls experienced pwms clinical concern considering current strain healthcare system findings study highlight importance monitoring falls potential telerehabilitation persons ms covid19,0.0
efficacy assisted reproduction women wide spectrum chronic diseases review clin epidemiol 2021 jun 23 13477500 doi 102147 cleps310795 ecollection 2021abstractassisted reproductive technology art treatments women underlying chronic diseases become increasingly frequent objective review provide overview literature examining chance live born child art women chronic diseases compared women receiving art focused prevalent chronic diseases women reproductive years ie ulcerative colitis crohns disease rheumatoid arthritis multiple sclerosis epilepsy hyperthyroidism hypothyroidism diabetes mellitus secondly studied chance successful implantation literature search performed database pubmedgov including studies published october 2020 title abstracts 58 papers reviewed 37 papers excluded 8 studies excluded fulltext evaluation 13 papers eligible review results indicate women ulcerative colitis crohns disease rheumatoid arthritis hyperthyroidism diabetes mellitus type 2 might problems low implantation rate early embryo development art contrary studies women hypothyroidism diabetes mellitus type 1 epilepsy suggest equivalent chance live birth compared women undergoing art possible explanation behind differences reside diseasespecific dysregulation innate adaptive immune system knowledge first review art women chronic diseases disclosed evidence area indeed sparse encourage others examine live birth art women chronic diseasespmid34194244 pmcpmc8236837 doi102147 cleps310795,0.0
multiple sclerosis neuromyelitis optica spectrum disorder covid19 pandemic year czech republic abstractbackgroundwhen novel coronavirus disease 2019 covid19 appeared concerns course patients multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd arose study aimed evaluate incidence severity risk factors severe covid19 course among ms nmosd patientsmethodsfrom march 1 2020 february 28 2021 12 ms centres representing 70 czech ms nmosd population reported laboratoryconfirmed covid19 cases via czech nationwide register ms nmosd patients remus main outcome covid19 severity assessed 8point scale cutoff 4 radiologically confirmed pneumonia according world health organisations covid19 severity assessmentresultswe identified 958 ms 13 nmosd patients 50 ms 4 nmosd patients pneumonia 3 ms 2 nmosd patients died incidence covid19 among patients ms seems similar general czech population multivariate logistic regression determined higher body mass index bmi 107 95 ci 100114 older age per 10 years 201 95 ci 141291 highdose glucocorticoid treatment 2 months covid19 onset 283 95 ci 010748 anticd20 therapy 704 95 ci 3101587 independent variables associated pneumonia ms patients increase odds pneumonia anticd20 treated ms patients compared patients diseasemodifying therapy age sex bmi highdose glucocorticoid treatment 2 months covid19 onset presence pulmonary comorbidity confirmed propensity score matching 890 95 ci 3043324 reports covid19 infection patients nmosd scarce however data available now suggest high risk severe covid19 course well higher mortality rate among nmosd patients cohort 4 nmosd patients 3077 severe covid19 course 2 patients 1539 diedconclusion majority ms patients mild covid19 course contrary nmosd patients however higher bmi age anticd20 therapy highdose glucocorticoid treatment 2 months covid19 onset associated pneumonia based study already started early administration antisarscov2 monoclonal antibodies preferential vaccination risk group patients,0.0
adapting definition multimorbidity development localitybased consensus selecting included long term conditions background defining multimorbidity proved elusive spite attempts standardise definitions national studies broad definition required capture national diversity locally based studies definition may need reflect demographic morbidity patterns aimed define multimorbidity inner city multiethnic deprived young age community typical many large citiesmethodswe used scoping literature review identify international literature standards guidelines long term condition ltc definitions inclusion multimorbidity definition consensus categorised high medium low consensus depending number literature sources citing ltc findings presented workshop consisting local health service stakeholders asked select ltcs inclusion second stage review second stage ltc tested seven evaluation domains prevalence impact preventability treatment burden progression multiple ltcs impact younger people data quality domains used create 12 target criteria ltc rankings according consensus group target criteria scores presented second workshop final decision ltc inclusionresultsthe literature review identified 18 literature sources citing 86 ltcs 11 excluded ltc clusters remainder allocated consensus groupings 13 ltcs high consensus cited 11 sources 15 medium consensus cited 510 sources 47 low consensus cited 5 sources first workshop excluded 31 ltcs remaining 44 ltcs consisted 13 high consensus ltcs high target score score 612 15 medium consensus ltcs 11 high target scores 16 low consensus ltcs 6 high target scoresthe final workshop selected 12 high consensus conditions 12 medium consensus ltcs 10 high target scores 8 low consensus ltcs 3 high target scores producing final selection 32 ltcsconclusionsredefining multimorbidity urban context ensures local relevance may diminish national generalisability describe detailed ltc selection process generalisable contexts local national,0.0
google search behavior meningitis vaccines infodemiological study background internet made significant contributions towards health education analyzing pattern online behavior regarding meningitis vaccinations may worthwhile hypothesized online search patterns meningitis correlated number cases search patterns related vaccinesmethodsthis infodemiological study determined relationship among online search interest meningitis worldwide number cases associated vaccines using google trends search volume indices svis evaluated search queries meningitis pneumococcal vaccine bcg vaccine meningococcal vaccine influenza vaccine january 2021 covering january 2008 december 2020 spearman rank correlation used determine correlations queriesresultsthe worldwide search interest meningitis 2008 2020 showed average svi 46 88 searched topics symptoms vaccines infectious agents svis 100 52 39 respectively top three countries highest search interest ghana kazakhstan kenya weak statistically significant correlations meningitis bcg 0369 p 0001 meningococcal 0183 p 005 vaccines statistically significant associations number cases influenza vaccine pneumococcal vaccineconclusionthe relationships among google svis meningitis related vaccines number cases data inconsistent remained unclear future infodemiological studies may expand scopes social media semantics big data robust conclusions,0.0
longstanding nonunion metatarsal fractures adult patient autosomal dominant osteopetrosis case report jbjs case connect 2021 jun 23 11 2 doi 102106 jbjscc2000842abstractcase osteopetrosis genetic condition impairs bone turnover result defects osteoclast function abnormal ossification bone autosomal dominant osteopetrosis often mild however impaired fracture healing increased density hardness osteopetrotic bone present technical challenges surgeons leading complications nonoperative operative treatment modalities case report describe patient treated empirically ultrasonic bone stimulation nonunion fractures multiple metatarsals failure conventional therapyconclusion ultrasonic bone stimulation may role optimizing nonoperative management osteopetrosisrelated fractures adultspmid34161309 doi102106 jbjscc2000842,0.0
socioeconomic determinants schistosoma mansoni infection using multiple correspondence analysis among rural western kenyan communities evidence householdbased study plos one 2021 jun 23 16 6 e0253041 doi 101371 journalpone0253041 ecollection 2021abstractbackground socioeconomic inequality including wealth distribution barrier implementation health policies wealth distribution can measured effectively using household data durable assets compared methods analysing socioeconomic status ses using durable assets multiple correspondence analysis mca can create reliable wealth quintiles therefore evaluated socioeconomic determinants schistosoma mansoni using mca household data among adult population western kenya hypothesis study mca useful predictor s mansoni prevalence intensitymethodology twelve villages 6 villages showed greatest decrease s mansoni prevalence responder villages 6 villages showed relatively lower decrease hotspot villages year 2011 2015 randomly selected study according previous schistosomiasis consortium operational research elimination score report western kenya village convenience sampling used identify 50 adults 50 households inclusion study interview questionnaire based upon mca indicators conducted one stool sample 600 adults examined based four slides s mansoni eggs using kato katz technique mean eggs per gram epg calculated taking average readings four slides log binomial regression model used identify influence various agegroups 30 years 3060 years 60 years household size wealth class occupation education status main water supply sex subcounty residence s mansoni infection epg compared across variables significant based multivariate log binomial model analysis using mixed modelprincipal findings overall prevalence s mansoni 413 significantly higher prevalence s mansoni associated males aged 30 years use unsafe water sources unprotected wells lakes rivers residents rachuonyo north hotspot villages earning livelihood fishing sex household size significant predictors multivariate model males associated significantly higher prevalence compared females apr 137 95 ci 114166 addition households least four persons higher prevalence compared less four apr 129 95 ci 103161 however difference prevalence wealth classes broadly divided poor less poor categories intensity infection mean epg also significantly higher among males younger age group rachuonyo north residents hotspot villagesconclusion socioeconomic status based mca model contributing factor s mansoni prevalence intensity possibly study populations sufficiently dissimilar use convenience sampling identify participants also contributed lack significant findingspmid34161354 doi101371 journalpone0253041,0.0
neuroinflammationdriven lymphangiogenesis cns diseases front cell neurosci 2021 jun 23 15683676 doi 103389 fncel2021683676 ecollection 2021abstractthe central nervous system cns undergoes immunosurveillance despite lack conventional antigen presenting cells lymphatic vessels cns parenchyma additionally cns bathed cerebrospinal fluid csf csf continuously produced consequently must continuously clear maintain fluid homeostasis despite lack conventional lymphatics neuroinflammation often accumulation fluid antigens immune cells affected areas brain parenchyma failure effectively drain factors may result edema prolonged immune response adverse clinical outcome observed conditions including traumatic brain injury ischemic hypoxic brain injury cns infection multiple sclerosis ms brain cancer consequently renewed interest surrounding expansion lymphatic vessels adjacent cns now thought central regulating drainage fluid cells waste cns lymphatic vessels found cribriform plate dorsal dural meninges base brain around spinal cord implicated important roles various cns diseases review discuss contribution meningeal lymphatics processes steadystate conditions neuroinflammation well discuss many still unknown aspects regarding role meningeal lymphatics neuroinflammation specifically focus observed phenomenon lymphangiogenesis subset meningeal lymphatics near cribriform plate neuroinflammation discuss potential roles immunosurveillance fluid clearance access csf cns compartments propose manipulating cns lymphatics may new therapeutic way treat cns infections stroke autoimmunitypmid34248503 pmcpmc8261156 doi103389 fncel2021683676,0.0
ultrastructural characterization human oligodendrocytes progenitor cells preembedding immunogold front neuroanat 2021 jun 23 15696376 doi 103389 fnana2021696376 ecollection 2021abstractoligodendrocytes myelinating cells central nervous system provide trophic metabolic structural support neurons several pathologies multiple sclerosis ms cells severely affected fail remyelinate thereby leading neuronal death gold standard studying remyelination gratio measured means transmission electron microscopy tem therefore studying fine structure oligodendrocyte population human brain different stages tem key feature field study study ultrastructure oligodendrocytes progenitors myelin 10 samples human white matter using nine different markers oligodendrocyte lineage ng2 pdgfr a2b5 sox10 olig2 bcas1 apc cc1 mag mbp findings show human oligodendrocytes constitute heterogeneous population within human white matter stages differentiation present characteristic features can used identify tem study sheds light cells interact cells within human brain clarify fine characteristics glial cell typespmid34248510 pmcpmc8262677 doi103389 fnana2021696376,1.0
glutamate signaling via ampar subunit glur4 regulates oligodendrocyte progenitor cell migration developing spinal cord oligodendrocyte progenitor cells opcs specified discrete precursor populations gliogenesis migrate extensively origins ultimately distributing throughout brain spinal cord early development subsequently subset opcs differentiates mature oligodendrocytes myelinate axons process necessary efficient neuronal signaling organism survival previous studies identified several factors influence opc development including excitatory glutamatergic synapses form neurons opcs myelination however little known glutamate signaling affects opc migration myelination study use vivo timelapse imaging zebrafish conjunction genetic pharmacological perturbation investigate opc migration myelination glur4a ionotropic glutamate receptor subunit disrupted studies observed gria4a mutant embryos larvae displayed abnormal opc migration altered dorsoventral distribution spinal cord genetic mosaic analysis confirmed effects cellautonomous identified voltagegated calcium channels downstream glutamate receptor signaling opcs rescue migration myelination defects observed glutamate signaling perturbed results offer new insights complex system neuronopc interactions reveal cellautonomous role glutamatergic signaling opcs neural developmentsignificance statement migration oligodendrocyte progenitor cells opcs essential process development leads uniform oligodendrocyte distribution sufficient myelination central nervous system function demonstrate ampa receptor ampar subunit glur4a important driver opc migration myelination vivo activated voltagegated calcium channels downstream glutamate receptor signaling mediating migration,1.0
metabolic control smoldering neuroinflammation front immunol 2021 jun 23 12705920 doi 103389 fimmu2021705920 ecollection 2021abstractcompelling evidence exists patients chronic neurological conditions includes progressive multiple sclerosis display pathological changes neural metabolism mitochondrial function however unknown similar degree metabolic dysfunction occurs also nonneural cells central nervous system specifically remains clarified full extent metabolic changes tissueresident microglia infiltrating macrophages prolonged neuroinflammation eg level chronic active lesions ii whether alterations underlie unique pathogenic phenotype amenable therapeutic targeting herein discuss cell metabolism mitochondrial function govern function chronic active microglia macrophages brain infiltrates identify new metabolic targets therapeutic approaches aimed reducing smoldering neuroinflammationpmid34249016 pmcpmc8262770 doi103389 fimmu2021705920,0.0
encephalitis myelitis young woman overlap syndrome thyroiditis occult tumor national multiple sclerosis society case conference proceedings neurol neuroimmunol neuroinflamm 2021 jun 23 8 5 e1026 doi 101212 nxi0000000000001026 print 2021 julno abstractpmid34162741 doi101212 nxi0000000000001026,0.0
potential implications quercetin autoimmune diseases front immunol 2021 jun 23 12689044 doi 103389 fimmu2021689044 ecollection 2021abstractautoimmune diseases worldwide health problem growing rates morbidity characterized breakdown dysregulation immune system although etiology pathogenesis remain unclear application dietary supplements gradually increasing patients autoimmune diseases mainly due positive effects relatively safety low cost quercetin natural flavonoid widely present fruits herbs vegetables shown wide range beneficial effects biological activities including antiinflammation antioxidation neuroprotection several recent studies quercetin reportedly attenuated rheumatoid arthritis inflammatory bowel disease multiple sclerosis systemic lupus erythematosus humans animal models review summarizes evidence pharmacological application quercetin autoimmune diseases supports view quercetin may useful prevention treatmentpmid34248976 pmcpmc8260830 doi103389 fimmu2021689044,1.0
case report successful stabilization marburg variant multiple sclerosis ocrelizumab following highdose cyclophosphamide rescue front neurol 2021 jun 23 12696807 doi 103389 fneur2021696807 ecollection 2021abstractthe marburg variant multiple sclerosis marburg ms aggressive form ms often leading death soon onset describe case 26yearold marburg ms patient presenting severe neurological deficits requiring intensive care spite 100 gadoliniumenhancing mri lesions patient recovered almost completely upon highdose cyclophosphamide hicy rescue treatment four consecutive days 50 mg kg day cumulative absolute dose 14 g following acute treatment disease stabilized b cell depletion using ocrelizumab clinical amelioration reflected decrease mri activity marked decline serum neurofilament light chain levels hicy rescue treatment followed ocrelizumab maintenance therapy prevented permanent disability achieved almost complete clinical drastic radiological improvement marburg ms patientpmid34248832 pmcpmc8260950 doi103389 fneur2021696807,1.0
evidence economic value endoflife palliative care interventions narrative review reviews background demand palliative care increases information needed efficient different types palliative care models providing care dying patients caregivers evidence economic value treatments interventions key informing resource allocation ultimately improving quality efficiency healthcare delivery assessed available evidence economic value palliative endoflife care interventions across various settingsmethodsreviews published 2000 2019 included included reviews focused costeffectiveness intervention costs healthcare resource use two reviewers extracted data independently duplicate included studies data key characteristics studies extracted including aim study design population type intervention comparator cost effectiveness resource use main findings conclusionsresultsa total 43 reviews included analysis overall evidence costeffectiveness relates homebased interventions suggests offer substantial savings health system including decrease total healthcare costs resource use improvement patient caregivers outcomes evidence interventions delivered across settings generally inconsistentconclusionssome palliative care models may contribute dual improvement quality care via lower rates aggressive medicalization last phase life accompanied reduction costs hospitalbased palliative care interventions may improve patient outcomes healthcare utilization costs need greater consistency reporting outcome measures informal costs caring costs associated hospice,0.0
peripheral administration sod1 aggregates transmit pathogenic aggregation cns sod1 transgenic mice abstractthe deposition aggregated proteins common neuropathological denominator neurodegenerative disorders experimental evidence suggests disease propagation involves prionlike mechanisms cause spreading templatedirected aggregation specific diseaseassociated proteins transgenic tg mouse models superoxide dismutase1 sod1 linked amyotrophic lateral sclerosis als inoculation minute amounts human sod1 hsod1 aggregates spinal cord peripheral nerves induces premature alslike disease templatedirected hsod1 aggregation spreads along neuroaxis infectious nature spreading pathogenic aggregates might implications safety laboratory medical staff recipients donated blood tissue possibly close relatives caregivers investigate whether transmission alslike disease unique spinal cord peripheral nerve inoculations hsod1 aggregation might spread periphery central nervous system cns inoculated hsod1 aggregate seeds peritoneal cavity hindlimb skeletal muscle spinal cord adult tg mice expressing mutant hsod1 although used 8000 times higher dosecompared lowest dose transmitting disease spinal cord inoculationsthe peripheral inoculations transmit seeded aggregation cns premature alslike disease hsod1 tg mice hsod1 aggregation detected liver kidney skeletal muscle sciatic nerve explore potential reasons lack disease transmission examined stability hsod1 aggregates found highly vulnerable proteases detergent findings suggest exposed individuals personnel handling samples als patients low risk potential transmission seeded hsod1 aggregation,0.0
singlecellresolution fate map endoderm reveals demarcation pancreatic progenitors cell cycle proc natl acad sci u s 2021 jun 22 118 25 e2025793118 doi 101073 pnas2025793118abstracta progenitor cell generate certain type multiple types descendant cells embryonic development make descendant cell types developmental trajectories every single progenitor cell clear remains ultimate goal developmental biology characterizations descendant cells produced uncommitted progenitor full germ layer represent big step toward goal focus early foregut endoderm generates foregut digestive organs including pancreas liver foregut ductal system distinct lineages using unbiased singlecell labeling techniques label every individual zebrafish foregut endodermal progenitor cell 216 cells visibly trace distribution number descendant cells hence singlecellresolution fate proliferation maps early foregut endoderm established progenitor regions foregut digestive organ precisely demarcated maps indicate pancreatic endocrine progenitors featured cell cycle state long g1 phase manipulating durations g1 phase modulates pancreatic progenitor populations study illustrates foregut endodermal progenitor cell fate singlecell resolution precisely demarcates different progenitor populations sheds light mechanistic insights pancreatic fate determinationpmid34161274 doi101073 pnas2025793118,0.0
characterisation mesenchymal stromal cells clinical trial reports analysis published descriptors background mesenchymal stem stromal cells widely used cell therapy date heterogeneous variations growth potential differentiation capacity protein expression profile depending tissue source production process nomenclature defining characteristics debated almost 20 years yet generic term msc used cover wide range cellular phenotypes documented lack definition cellular populations used clinical trials study evaluated extent characterisation cellular population study drugmethodsa literature search clinical trials involving mesenchymal stem stromal cells refined 84 papers upon application predefined inclusion exclusion criteria data extracted covering background trial information including location phase indication tissue source details clinical cell population characterisation expression surface markers viability differentiation assays potency functionality assays descriptive statistics applied tests association groups explored using fishers exact test count data simulated p valueresultstwentyeight studies 333 include characterisation data fortyfive 536 reported average values per marker cell lots used trial 11 131 studies included individual values per cell lot viability reported 57 studies differentiation discussed osteogenesis 29 papers adipogenesis 27 chondrogenesis 20 functional assays arose 7 papers 8 extent characterisation related clinical phase development assessment functionality limited always relate likely mechanism actionconclusionsthe extent characterisation poor variable findings concur fields including bone marrow aspirate plateletrich plasma therapy discuss potential implications findings use mesenchymal stem stromal cells regenerative medicine importance characterisation transparency comparability literaturegraphical abstract,0.0
schizophrenia gut microbiota new opportunities optogenetic manipulations gutbrain axis abstractschizophrenia research arose twentieth century currently rapidly developing focusing many parallel research pathways evaluating various concepts disease etiology today relatively good knowledge generation positive negative symptoms patients schizophrenia however neural basis pathophysiology schizophrenia especially cognitive symptoms still poorly understood finding new methods uncover physiological basis mental inabilities related schizophrenia urgent task modern neuroscience lack specific therapies cognitive deficits disease researchers begun investigating functional crosstalk nmdars gabaergic neurons associated schizophrenia different resolutions another direction gut microbiota getting increasing interest neuroscientists recent findings highlighted role gutbrain axis gut microbiota playing crucial role several psychopathologies including schizophrenia autismthere also investigations potential therapies aimed normalizing altered microbiota signaling enteric nervous system ens central nervous system cns probiotics diets fecal microbiota transplantation fmt currently common therapies interestingly rodent models binge feeding optogenetic applications shown affect gut colony sensitivity thus increasing colonic transit review recent findings gut microbiotaschizophrenia relationship using vivo optogenetics moreover evaluate manipulating actors either brain gut might improve potential treatment research research techniques will increase knowledge gut microbiota can manipulate gaba production therefore accompany changes cns gabaergic activity,0.0
sativex nabiximols cannabinoid oromucosal spray patients resistant multiple sclerosis spasticity belgian experience background retrospective study evaluates patientreported outcomes patients multiple sclerosis ms spasticity treated cannabinoid oromucosal spray sativex usan name nabiximols sufficiently responding previous antispasticity medicationsmethodsof 276 patients eight centers belgium began treatment prior 31 december 2017 effectiveness assessment data available 238 patients test period 4 8 12 weeks smaller patient cohorts continued treatment 6 12 monthsresultsmean 010 spasticity numerical rating scale nrs scores improved 81 baseline 52 week 4 46 week 8 41 week 12 mean euroqol visual analogue scale eq vas scores increased 39 baseline 52 week 4 57 week 8 59 week 12 mean nrs eq vas scores remained 12 weeks range patients longerterm data average dose cannabinoid oromucosal spray 6 sprays day 93 276 patients initial prescription 337 discontinued treatment week 12 within first 8 weeks mainly due lack effectiveness week 12 171 74 230 effectiveness evaluable patients reported clinically meaningful response corresponding 30 nrs improvement tolerability cannabinoid oromucosal spray consistent known safety profileconclusionsmore 60 patients ms started addon treatment cannabinoid oromucosal spray reported clinically relevant symptomatic effect continued treatment 12 weeks,1.0
brain microstructural metabolic alterations detected vivo onset first demyelinating event brain 2021 apr 27awab043 doi 101093 brain awab043 online ahead printabstractin early multiple sclerosis clearer understanding normalbrain tissue microstructural metabolic abnormalities will provide valuable insights pathophysiology used multiparametric quantitative mri detect alterations brain tissues patients first demyelinating episode acquired neurite orientation dispersion density imaging investigate morphology neurites dendrites axons 23na mri estimate total sodium concentration reflection underlying changes metabolic function crosssectional study enrolled 42 patients diagnosed clinically isolated syndrome multiple sclerosis within 3 months first demyelinating event 16 healthy controls physical cognitive scales assessed 3 t acquired brain spinal cord structural scans neurite orientation dispersion density imaging thirtytwo patients 13 healthy controls also underwent brain 23na mri measured neurite density orientation dispersion indices total sodium concentration brain normalappearing white matter white matter lesions grey matter used linear regression models adjusting brain parenchymal fraction lesion load spearman correlation tests significance level p 001 patients showed higher orientation dispersion index normalappearing white matter including corpus callosum also showed lower neurite density index higher total sodium concentration compared healthy controls grey matter compared healthy controls patients demonstrated lower orientation dispersion index frontal parietal temporal cortices lower neurite density index parietal temporal occipital cortices higher total sodium concentration limbic frontal cortices brain volumes differ patients controls patients higher orientation dispersion index corpus callosum associated worse performance timed walk test p 0009 b 001 99 confidence interval 00001 002 independent brain lesion volumes higher total sodium concentration left frontal middle gyrus associated higher disability expanded disability status scale rs 05 p 0005 increased axonal dispersion found normalappearing white matter particularly corpus callosum also axonal degeneration total sodium accumulation association increased axonal dispersion corpus callosum worse walking performance implies morphological metabolic alterations structure mechanistically contribute disability multiple sclerosis brain volumes neither altered related disability patients findings suggest two advanced mri techniques sensitive detecting clinically relevant pathology early multiple sclerosispmid33903905 doi101093 brain awab043,1.0
imaging meningeal inflammation cns autoimmunity identifies therapeutic role btk inhibition brain 2021 mar 16awab045 doi 101093 brain awab045 online ahead printabstractleptomeningeal inflammation multiple sclerosis associated worse clinical outcomes greater cortical pathology despite progress identifying process multiple sclerosis patients using postcontrast fluidattenuated inversion recovery imaging early trials attempting target meningeal inflammation unsuccessful lack appropriate model systems screen potential therapeutic agents targeting meningeal inflammation utilized ultrahigh field 117 t mri perform postcontrast imaging sjl j mice experimental autoimmune encephalomyelitis induced via immunization proteolipid protein peptide plp139151 complete freunds adjuvant imaging performed crosssectional longitudinal fashion time points ranging 2 14 weeks postimmunization following imaging euthanized animals collected tissue pathological evaluation revealed dense cellular infiltrates corresponding areas contrast enhancement involving leptomeninges areas meningeal inflammation contained b cells b220+ t cells cd3+ myeloid cells mac2+ also noted features consistent tertiary lymphoid tissue within areas namely presence peripheral node addressinpositive structures cxc motif chemokine ligand13 cxcl13 producing cells fdcm1+ follicular dendritic cells cortex adjacent areas meningeal inflammation identified astrocytosis microgliosis demyelination evidence axonal stress damage since areas meningeal contrast enhancement persisted several weeks longitudinal experiments utilized model test effects therapeutic intervention established meningeal inflammation randomized mice evidence meningeal contrast enhancement mri scans performed 6 weeks postimmunization treatment either vehicle evobrutinib bruton tyrosine kinase btk inhibitor period 4 weeks mice underwent serial imaging examined effect treatment areas meningeal contrast enhancement noted significant reduction evobrutinib group compared vehicle 30 reduction versus 5 increase p 0003 used ultrahigh field mri identify areas meningeal inflammation track time sjl j mice experimental autoimmune encephalomyelitis used model identify btk inhibition novel therapeutic approach target meningeal inflammation results study provide support future studies multiple sclerosis patients imaging evidence meningeal inflammationpmid33724342 doi101093 brain awab045,1.0
differences correlates fatigue relapsing progressive forms multiple sclerosis abstractbackgroundfatigue one prevalent impactful symptoms people multiple sclerosis ms yet fatigue less understood progressive forms ms studies explored extent ms disease course associated fatigue current study aimed 1 describe fatigue severity fatigue interference extent fatigue interferes individualsnull physical mental social activities people progressive ms primary progressive ms secondary progressive ms 2 compare fatigue severity fatigue interference people progressive forms ms people relapsingremitting ms rrms 3 identify factors associated fatigue severity fatigue interference people progressive forms ms rrmsmethodssecondary analysis baseline data participants ms n573 progressive forms ms n142 rrms n431 surveybased longitudinal study healthy aging people physical disability primary outcomes average fatigue severity 010 numerical rating scale fatigue interference promis fatigue short form correlates variables across demographic biopsychosocial domains collected validated selfreported measures statistical methods included ttest chisquare analyses compare fatigue severity fatigue interference people progressive ms rrms multiple regression analyses examine association variables fatigue severity fatigue interferenceresultsparticipants progressive forms ms reported moderate severe levels average fatigue severity 5928 elevated levels fatigue interference tscore 58279 group differences people progressive ms rrms average fatigue severity fatigue interference common factors associated greater fatigue severity lower income unemployed shorter disease duration greater disability greater sleep disturbance common factors associated fatigue interference younger age lower income unemployed greater disability lower alcohol consumption smoker greater sleep disturbance progressive forms ms longer ms disease duration associated lower average fatigue severity b008 t 532 369 p 001 college degree higher associated higher fatigue interference b284 t 520 223 p026 conclusionin sample fatigue severity fatigue interference similar progressive forms ms rrms future research consider interventions work fatigue management people relapsing forms ms work similarly people progressive forms ms,0.0
18fflorbetapir pet mri quantitatively monitoring myelin loss recovery patients multiple sclerosis longitudinal study background amyloid positron emission tomography pet can measure invivo demyelination patients multiple sclerosis ms however value 18flabeled amyloid pet tracer 18fflorbetapir longitudinal study monitoring myelin loss recovery confirmed methods march 2019 september 2020 twentythree patients ms nine healthy controls hcs underwent hybrid pet mri baseline expanded disability status scale edss assessment eight 23 patients underwent followup pet mri distribution volume ratio dvr standard uptake value ratio suvr 18fflorbetapir damaged white matter dwm normalappearance white matter nawm obtained dynamic static pet acquisition diffusion tensor imagingderived parameters also calculated data expressed mean standard deviation 99 confidence interval 99ci finding mean dvr 108 012 99ci 102 114 mean suvr dwm lesions lower nawm patients ms 125 010 99ci 120 131 hcs 129 008 99ci 123 136 trend toward lower mean fractional anisotropy 37495 4530 vs 41907 483 higher mean radial diffusivity 045 005 vs 040 001 nawm patients ms hcs found dvr decreased dwm lesions higher md rho 0261 99ci 0362 0144 higher ad rho 0200 99ci 0318 0070 higher rd rho 0198 99ci 0313 0075 patients edss scores reduced b 004 99ci 0005 0084 decreased index global demyelination longitudinal study interpretation exploratory study suggests dynamic 18fflorbetapir pet mri may promising tool quantitatively monitoring myelin loss recovery patients ms funding shanghai pujiang program shanghai municipal key clinical specialty shanghai shuguang plan project shanghai health family planning commission research project clinical research plan shdc frenchchinese program xu guangqi,1.0
comparative assessment vitro bbb tight junction integrity following exposure cigarette smoke ecigarette vapor quantitative evaluation protective effects metformin using smallmolecularweight paracellular markers background bloodbrain barrier bbb plays critical role protecting central nervous system cns bloodborne agents potentially harmful xenobiotics groups previous data shown tobacco smoke ts electronic cigarettes ec affect bbb integrity increase stroke incidence considered risk factor multiple cns disorders metformin also found abrogate adverse effects ts ecmethodswe used sucrose mannitol paracellular markers quantitatively assess ts ecs impact bbb invitro specifically used quantitative platform determine harmful effects smoking bbb study protective effect metformin using transwell system ipscsderived bmecs assessed ts ecs effect sucrose mannitol permeability without metformin pretreatment different time points concurrently using immunofluorescence western blot wb techniques evaluated expression distribution tight junction proteins including zo1 occludin claudin5resultsour data showed ts ec negatively affect sucrose mannitol permeability starting 6 h 24 h loss barrier integrity associated reduction teer values overall expression level zo1 occludin significantly downregulated distribution zo1 altered discontinuation patterns evident imaging contrast occludin claudin5 expression significantly decreased ts ec demonstrated wb dataconclusionin agreement previous studies data showed metformin counteract negative impact ts ec bbb integrity thus suggesting possibility repurposing drug afford cerebrovascular protection,0.0
medial septal gabaergic neurons reduce seizure duration upon optogenetic closedloop stimulation brain 2021 mar 26awab042 doi 101093 brain awab042 online ahead printabstractseizures can emerge multiple large foci temporal lobe epilepsy complicating focally targeted strategies surgical resection modulation activity specific hippocampal neuronal populations genetic optogenetic techniques evaluate strategy optogenetic activation medial septal gabaergic neurons provide extensive projections throughout hippocampus used control seizures utilized chronic intrahippocampal kainate mouse model temporal lobe epilepsy results spontaneous seizures often case human patients presents hippocampal sclerosis medial septal gabaergic neuron populations immunohistochemically labelled reduced epileptic conditions genetic labelling mruby medial septal gabaergic neuron synaptic puncta imaging across rostral caudal extent hippocampus also indicated unchanged number putative synapses epilepsy furthermore optogenetic stimulation medial septal gabaergic neurons consistently modulated oscillations across multiple hippocampal locations control epileptic conditions finally wireless optogenetic stimulation medial septal gabaergic neurons upon electrographic detection spontaneous hippocampal seizures resulted reduced seizure durations propose medial septal gabaergic neurons novel target optogenetic control seizures temporal lobe epilepsypmid33769452 doi101093 brain awab042,0.0
review phase iii clinical trials outcomes patients secondary progressive multiple sclerosis abstractobjective satisfyingly effective treatments exist patients secondary progressive multiple sclerosis spms goal conducting review highlight clinical outcomes study design may applied future phase iii clinical trials patients spmsmethods review available literature phase iii clinical trials since 1990 specifically studied patients spms pubmed clinicaltrialsorg searched using appropriate termsresults expanded disability status scale edss often used outcome measure time confirmed disability progression three months used often components multiple sclerosis functional composite msfc next frequent primary outcome measure used patient reported outcomes pros frequently used secondary outcome measures specific pros successful others mri measures related brain parenchymal volume recently started used phase iii clinical trialsconclusions successful trials may related patient selection less inflammatory disease confounds comparison successful trials time confirmed disability three months changes composite msfc reasonable primary outcome measures use future spms trials suggestion msfc may sensitive progressive disease changes pros mri measures following brain parenchymal volume reasonable secondary outcome measures incorporate future phase iii trials spms,0.0
patients partners research patient caregiver perceptions research engagement role psychosocial states participation j patient exp 2021 jun 22 823743735211018084 doi 101177 23743735211018084 ecollection 2021abstractmultiple sclerosis ms one common nontraumatic disabling diseases diagnosed adults selfempowered patients families valued members ms research team objective study explore patient family perceptions influence psychosocial state willingness research partners researchers conducted 5 focus groups ms patients family upper midwest chapter national multiple sclerosis society researchers asked questions addressing psychosocial factors influencing ability willingness work ms researchers partners relevant themes identified including comfort level individuals formulating research questions comfort level engaging research understanding meaning research selfperception skills research training knowledge needs findings study support role ms patients perspectives ms understanding science ms role psychosocial states factors patient identified key ability active engaged willing research participantspmid34235248 pmcpmc8227401 doi101177 23743735211018084,0.0
cannabinoids bladder symptoms multiple sclerosis abstractbackgroundresearch health benefits cannabis limited use remains restricted illegal countries medical cannabis legal canada since 2001 recreational use became legal october 2018 data support biological mechanism cannabinoids can impact various symptoms ms evidence effectiveness cannabis treatment bladder symptoms remains unsettled conducted exploratory study describe current trends cannabis product consumption among people ms pwms association perceived benefits ms symptomsmethodsa crosssectional survey study pwms recruited ms clinic calgary alberta canada undertaken logistic regression analyses performed assess associations cannabis consumption improvement bladder function symptomsresultsthere 775 respondents 2899 pwms contacted email among respondents 734 reported cannabis use past 3 months 275 375 respondents reported cannabis use prior 3 months 738 reported least weekly use cannabis among users 781 reported primary medical therapeutic indication consumption common modes cannabis consumption oraledible 690 smoked 571 593 used one mode consumption 26 used five different modes common reasons cannabis use sleep 583 pain 515 relaxation 444 muscle spasms 402 anxiety 338 depression 229 among 19 participants reported bladder symptoms main reason cannabis use 895 reported better bladder symptoms using cannabis cannabis consumption past 3 months associated twofold increased odds reporting improvement urinary frequency urinary urgency bladder leakage wetness pad use bladder emptyingconclusionscannabis commonly used survey study personal cannabis use among pwms patterns use dosing frequency mode delivery diverse among survey respondents pilot study provides initial glimpses real world therapeutic use cannabinoids among pwms bladder symptoms,0.0
primary headaches covid19 lockdown germany analysis data 2325 patients using electronic headache diary background lockdown measures due covid19 pandemic led lifestyle changes turn may impact course headache disorders aimed assess changes primary headache characteristics lifestyle factors covid19 lockdown germany using digital documentation mobile application app msensemain bodywe analyzed data smartphone users entered daily data app 28day period lockdown baseline first 28 days lockdown observation period analysis included change monthly headache days mhd observation period compared baseline also assessed changes monthly migraine days mmd use acute medication pain intensity addition looked changes sleep duration sleep quality energy level mood stress activity level outcomes compared using paired tteststhe analysis included data 2325 app users reported 701 sd 564 mhd baseline 689 547 mhd lockdown without significant changes p 0999 mmd headache migraine intensity neither showed significant changes days acute medication use reduced 450 388 baseline 427 381 observation period p 0001 app users reported reduced stress levels longer sleep duration reduced activity levels along better mood improved energy level first lockdown month p 0001 extension analysis users continued use msense every day 3 months initiation lockdown compared baseline subsequent months using repeatedmeasures anova 539 users headache frequency change significantly neither 611 510 mhd lockdown vs 607 517 mhd third lockdown month p 0688 anova migraine frequency headache migraine intensity acute medication use also different entire observation periodconclusiondespite slight changes factors contribute generation headache covid19related lockdown measures seem associated primary headache frequency intensity course 3 months,0.0
role hippocampal location radiation dose glioblastoma patients hippocampal atrophy background hippocampus critical organ irradiation thus explored changes hippocampal volume according dose delivered location relative glioblastomamethodsall patients treated glioblastoma surgery concomitant radiotherapy temozolomide adjuvant temozolomide hippocampi retrospectively delineated three mris performed baseline time relapse last mri available end followup total 98 96 82 hippocampi measured 49 patients included study respectively patients stratified three subgroups according dose delivered 40 hippocampus group 1 n 6 hippocampal d40 74 gy group 2 n 13 hcontra d40 74 gy group 3 n 30 d40 hippocampi 74 gyresultsregardless time measurement homolateral hippocampal volumes significantly lower contralateral tumor regardless side volumes last mri significantly lower measured baseline significant correlation among decrease hippocampal volume regardless side dmax p 0001 d98 p 0028 d40 p 00002 adjustment time mri correlations remained significant according d40 volume mrilast hippocampi decreased 4 mm3 gy overallconclusionsthere significant relationship radiotherapy dose decrease hippocampal volume however lowest doses hippocampi seem exhibit adaptive increase volume indicate plasticity effect consequently shielding least one hippocampus delivering lowest possible dose recommended cognitive function can preservedtrial registration retrospectively registered,0.0
il17 inhibits oligodendrocyte progenitor cell proliferation differentiation increasing k+ channel kv13 front cell neurosci 2021 jun 22 15679413 doi 103389 fncel2021679413 ecollection 2021abstractinterleukin 17 il17 signature cytokine th17 cells il17 level significantly increased inflammatory conditions cns including limited poststroke multiple sclerosis il17 detected direct toxicity oligodendrocyte ol lineage cells inhibition oligodendrocyte progenitor cell opc differentiation thus promotes myelin damage cellular mechanism il17 cns inflammatory diseases remains obscure voltagegated k+ kv channel 13 predominant kv channel ol potentially involved ol function cell cycle regulation kv13 t cells involves immunomodulation inflammatory progression role ol kv13 inflammationrelated pathogenesis fully investigated hypothesized il17 induces myelin injury kv13 activation test hypothesis studied involvement opc ol kv13 il17induced ol myelin injury vitro vivo kv13 currents channel expression gradually decreased opc development application il17 opc culture increased kv13 expression leading decrease akt activation inhibition proliferation myelin basic protein reduction prevented specific kv13 blocker 5 4phenoxybutoxy psoralen il17caused myelin injury validated lpcinduced demyelination mouse model particularly corpus callosum also mitigated aforementioned kv13 antagonist il17 altered kv13 expression resultant inhibitory effects opc proliferation differentiation may interrupting akt phosphorylating activation taken together results suggested il17 impairs remyelination promotes myelin damage kv13mediated ol myelin injury thus blockade kv13 potential therapeutic strategy inflammatory cns disease may partially attribute direct protection opc proliferation differentiation immunomodulationpmid34239419 pmcpmc8258110 doi103389 fncel2021679413,1.0
cortical involvement determines impairment 30 years clinically isolated syndrome brain 2021 apr 21awab033 doi 101093 brain awab033 online ahead printabstractmany studies report overlap mri clinical findings patients relapsingremitting multiple sclerosis rrms secondary progressive multiple sclerosis spms part reflective inclusion subjects variable disease duration short periods followup overcome limitations examined differences rrms spms relationship mri measures clinical outcomes 30 years first presentation clinically isolated syndrome suggestive multiple sclerosis sixtythree patients studied 30 years initial presentation clinically isolated syndrome 14 received disease modifying treatment time point twentyseven patients developed rrms 15 spms 21 experienced neurological events groups comparable terms age disease duration clinical assessment included expanded disability status scale 9hole peg test timed 25foot walk brief international cognitive assessment multiple sclerosis subjects underwent comprehensive mri protocol 3 t measuring brain white grey matter lesions volumes magnetization transfer ratio cervical cord involvement linear regression models used estimate age genderadjusted group differences clinical phenotypes 30 years stepwise selection determine associations large sets mri predictor variables physical cognitive outcome measures 30year followup greatest differences mri measures spms rrms number cortical lesions higher spms presence cortical lesions 100 sensitivity 88 specificity grey matter volume lower spms across subjects cortical lesions grey matter volume cervical cord volume explained 60 variance expanded disability status scale cortical lesions alone explained 43 grey matter volume cortical lesions gender explained 43 variance timed 25foot walk reduced cortical magnetization transfer ratios emerged significant explanatory variable symbol digit modality test explained 52 variance cortical involvement terms lesions atrophy appears main correlate progressive disease disability cohort individuals long followup homogeneous disease duration indicating target therapeutic interventionspmid33880511 doi101093 brain awab033,0.0
myelin content changes clinically isolated syndrome relapsing remitting multiple sclerosis associations lesion type severity visuomotor impairment abstractbackgroundcognitive disturbances occur patients relapsing remitting multiple sclerosis rrms clinically isolated syndrome cis multiechospinecho mese t2weighted sequence quantifies demyelination pathological hallmark ms used documentation potential relationship anatomically specific demyelinating changes cognitive impairment mspurposeto identify markers regional demyelination patients rrms cis relation clinical variables severity cognitive impairmentmethods materials37 rrms patients 39 cis patients 52 healthy controls hc examined using mese sequence long t2 myelin water fraction mwf values measured serving indices intra extracellular water content myelin content respectively focal white matter lesions 12 normal appearing white matter nawm areas patients hc comprehensive neuropsychological assessment administered patientsresultsrrms patients showed widespread long t2 increases mwf reductions nawm compared respective values hc p 0001 correlated total lesion volume among rrms patients illness duration correlated negatively mwf right hemisphere frontal periventricular nawm areas positively corresponding long t2 values mwf values lower cis compared hc group temporal frontal periventricular nawm areas focal demyelinating lesions displayed variable higher t2 lower mwf values compared nawm closely corresponding intensity t1 sequences reduced mwf values increased long t2 values right periventricular nawm significantly associated poor visuomotor performanceconclusionthe mese sequence affords accurate estimation myelin water content nawm focal lesions rrms cis patients means mwf long t2 values respectively providing sensitive index demyelination associated visuomotor deficits,1.0
computerized screening processing speed impairment sufficient identifying msrelated cognitive impairment clinical setting abstractbackgroundannual screening processing speed impairment psi recommended patients multiple sclerosis pwms however cognitive deficits pwms heterogeneous whether psi screening identifies patients impairment cognitive domains unclear objective study examine sensitivity specificity selfadministered computerized processing speed test pst identifying cognitive impairment defined comprehensive neuropsychological battery npt methodsninetyone pwms completed pst npt raw scores demographically adjusted cognitive impairment npt defined performance 5th percentile least one domain receiver operating characteristic roc analyses performed determine ability pst discriminate cognitively normal cn cognitively impaired psi cipsi cognitively impaired normal processing speed cipsn groupsresultscognitive impairment observed 231 pwms pst 429 npt pst demonstrated excellent ability discriminate cn 571 cipsi 209 groups area curve auc 086 p 0001 contrast pst unable discriminate cn cipsn 220 groups auc042 p032 conclusionthe pst demonstrates excellent ability detect psi pwms unable identify cognitively impaired pwms without psi highlighting importance developing additional screening measures,0.0
quantitative magnetic resonance imaging towards clinical application multiple sclerosis brain 2021 may 10awab029 doi 101093 brain awab029 online ahead printabstractquantitative mri provides biophysical measures microstructural integrity cns can compared across cns regions patients centres patients multiple sclerosis quantitative mri techniques relaxometry myelin imaging magnetization transfer diffusion mri quantitative susceptibility mapping perfusion mri complement conventional mri techniques providing insight disease mechanisms include presence extent diffuse damage cns tissue outside lesions normalappearing tissue ii heterogeneity damage repair focal lesions iii specific damage cns tissue components review summarizes recent technical advances quantitative mri existing pathological validation quantitative mri techniques emerging applications quantitative mri patients multiple sclerosis research clinical settings current level clinical maturity quantitative mri technique especially regarding integration clinical routine discussed aim provide better understanding quantitative mri may help clinical practice improving stratification patients multiple sclerosis assessment disease progression evaluation treatment responsepmid33970206 doi101093 brain awab029,1.0
alcohol consumption risk common autoimmune inflammatory diseasesevidence largescale genetic analysis totaling 1 million individuals front genet 2021 jun 22 12687745 doi 103389 fgene2021687745 ecollection 2021abstractpurpose observational studies suggested protective effect alcohol intake autoimmune disorders supported mendelian randomization mr analyses used 20 instrumental variables methods systemically interrogated putative causal relationship alcohol consumption four common autoimmune disorders using summarylevel data largest genomewide association study gwas conducted inflammatory bowel disease ibd rheumatoid arthritis ra multiple sclerosis ms systemic lupus erythematosus sle quantified genetic correlation examine shared genetic similarity constructed strong instrument using 99 genetic variants associated drinks per week applied several twosample mr methods additionally incorporated excessive drinking reflected alcohol use disorder identification test score results observed negatively shared genetic basis alcohol intake autoimmune disorders although none significant r g 007 002 disorders genetically predicted alcohol consumption associated slightly 1025 decreased risk onset yet associations significant metaanalyzing across ra ms ibd three th1related disorders yielded marginally significantly reduced effect 070 051095 p 002 excessive drinking appear reduce risk autoimmune disorders conclusions greatly augmented sample size substantially improved statistical power mr study convincingly support beneficial role alcohol consumption individual autoimmune disorder future studies may designed replicate findings understand causal effect disease prognosispmid34239545 pmcpmc8258244 doi103389 fgene2021687745,0.0
new classification cardiooncology syndromes abstractincreasing evidence suggests multifaceted relationship exists cancer cardiovascular disease cvd introduce 5tier classification system categorize cardiooncology syndromes cos represent aspects relationship cancer cvd cos type characterized mechanisms whereby abrupt onset progression cancer can lead cardiovascular dysfunction cos type ii includes mechanisms cancer therapies can result acute chronic cvd cos type iii characterized prooncogenic environment created release cardiokines high oxidative stress patients cardiovascular dysfunction cos type iv comprised cvd therapies diagnostic procedures associated promoting unmasking cancer cos type v characterized factors causing systemic genetic predisposition cvd cancer development framework may allow increased facilitation cancer care optimizing cardiovascular health focused treatment targeting cos type,0.0
approach sarscov2 vaccination patients multiple sclerosis front immunol 2021 jun 21 12701752 doi 103389 fimmu2021701752 ecollection 2021abstractfor year now severe acute respiratory syndrome coronavirus 2 sarscov2 causing coronavirus disease covid19 pandemic high mortality detrimental effects society economy individual lives great hopes placed vaccination one potent escape strategies pandemic multiple vaccines already clinical use however still lot insecurity safety efficacy vaccines patients autoimmune diseases like multiple sclerosis ms especially treatment immunomodulatory immunosuppressive drugs propose strategic approaches sarscov2 vaccination management ms patients encourage fellow physicians measure immune response patients notably humoral cellular responses considered since immunological equivalent protection sarscov2 infection vaccination still remains undefined will likely involve antiviral cellular immunity important gain insights vaccine response immunocompromised patients order able deduce sensible strategies vaccination futurepmid34234787 pmcpmc8256163 doi103389 fimmu2021701752,0.0
characteristics mhealth app use international sample people multiple sclerosis summarythe management multiple sclerosis ms progressed significantly emergence mhealth technologies uptake mhealth apps amongst people ms clinical demographic characteristics mhealth adopters unknown outside north america participants holism study queried mhealth apps use summarize mhealth app usage clinical demographic characteristics mhealth app adopters using descriptive statistics overall 31 respondents reported using mhealth app located australasia north america study provides insight regarding mhealth app usage within large international cohort people ms,0.0
cognitive function men nonmotor features parkinson#39 s disease bmj neurol open 2021 jun 21 3 1 e000112 doi 101136 bmjno2020000112 ecollection 2021abstractobjective subtle cognitive deficits can occur prodromal phase parkinsons disease pd commonly conjunction hyposmia however little known association cognitive function features suggestive prodromal pd evaluated association nonmotor prodromal pd features including hyposmia constipation probable rem sleep behaviour disorder prbd objective measures cognitive function selfreported cognitive declinemethods study population comprised 804 men responded telephone cognitive interview 20162017 participants included 680 individuals hyposmia 45 confirmed pd 124 men without hyposmia among men evaluated objective cognitive function subjective cognitive decline determine whether presence nonmotor features prodromal pd associated cognitive functioning analyses adjusted age physical activity body mass index smoking status coffee consumptionresults individuals nonmotor features prodromal pd worse objective subjective cognitive performance relative men without nonmotor features cognitive impairment particularly prevalent among individuals concurrent hyposmia prbd constipation multivariateadjusted or380 95 ci 152 947 objective poor cognitive function or871 95 ci 318 2383 subjective cognitive decline expected objective or791 subjective or1742 cognitive impairment also common among men confirmed pdconclusions study suggests cognition commonly affected individuals nonmotor prodromal pd features particularly multiple features presentpmid34250483 pmcpmc8217956 doi101136 bmjno2020000112,0.0
world brain day 2021 call stop multiple sclerosis world federation neurology wfn celebrates world brain day every july 22 focusing different theme year1 highlighted editorial 2 theme world brain day stop multiple sclerosis video wfn working jointly multiple sclerosis international federation msif well clinicians experts affiliated advocacy organisations throughout asia oceania europe africa americas many public awareness programmes educational social media activities promoting movement stop multiple sclerosis commencing july 22 2021 continuing october 2021 multiple sclerosis can occur age mean age diagnosis 32 yearsa time many people planning family building careers impact diagnosis affected individuals families can profound currently cure multiple sclerosis means people live disease many decades effective diseasemodifying treatments use can reduce disabling effects appreciably costs preclude access many people world brain day 2021 provides opportunity highlight urgent need early diagnosis advocate access health care education research importantly access effective treatments can substantially reduce disability compiled five key messages multiple sclerosis world brain day 2021 panel,0.0
hyperactivation monocytes macrophages mci patients contributes progression alzheimer#39 s disease background alzheimers disease ad common neurodegenerative disease ultimately manifesting clinical dementia despite considerable effort ample experimental data role neuroinflammation related systemic inflammation still unsettled implication microglia well recognized exact contribution peripheral monocytes macrophages still largely unknown especially concerning role various stages adobjectivesad develops decades clinical manifestation preceded subjective memory complaints smc mild cognitive impairment mci thus question arises peripheral innate immune response changes progression disease therefore investigate roles monocytes macrophages progression ad assessed phenotypes functions patients smc mci ad stages compared cognitively healthy controls also conceptualised idealised mathematical model explain functionality monocytes macrophages along progression diseaseresultswe show distinct phenotypic functional changes monocyte macrophage populations disease progresses higher free radical production upon stimulation already observed monocytes smc patients striking results show activation peripheral monocytes hyperactivation strongest mci group prodromal stage disease monocytes exhibit significantly increased chemotaxis free radical production cytokine production response tlr2 tlr4 stimulationconclusionour data suggest peripheral innate immune system activated progression smc mci ad highest levels activation mci subjects lowest ad patients parameters may used biomarkers holistic immune studies needed find best period disease clinical intervention,0.0
synergistic antiapoptosis effects amniotic epithelial stem cell conditioned medium ponesimod oligodendrocyte cells front pharmacol 2021 jun 21 12691099 doi 103389 fphar2021691099 ecollection 2021abstractmultiple sclerosis chronic inflammatory neurodegenerative disease central nervous system current treatment multiple sclerosis based antiinflammatory diseasemodifying treatments can regenerate myelin eventually neurons need new approaches axonal protection remyelination amniotic epithelial stem cells amniotic epithelial cells neuroprotective neurogenic agent proper source tissue engineering regenerative medicine due differentiation capability secretion growth factors aecs can candidate treatment ms moreover sphingosine1phosphate s1p receptor modulators recently approved fda ms ponesimod s1p receptor1 modulator acts selectively antiinflammatory agent provides suitable microenvironment function neuroprotective agents study due characteristics aecs considered treatment option ms conditioned medium aecs concurrently ponesimod used evaluate viability oligodendrocyte cell line induction cell death cuprizone cell viability treatment conditioned medium ponesimod increased compared untreated groups also results showed combination therapy cm ponesimod synergistic antiapoptotic effect oligodendrocyte cells combination treatment cm ponesimod reduced expression caspase3 caspase8 bax annexin v proteins increased relative bcl2 bax ratio indicating inhibition apoptosis possible mechanism action based promising results combination therapy amniotic stem cells ponesimode proper alternative multiple sclerosis treatmentpmid34234678 pmcpmc8255610 doi103389 fphar2021691099,1.0
intermediate uveitis etiology complications treatment outcomes colombian uveitis referral center clin ophthalmol 2021 jun 21 1525972605 doi 102147 opths309193 ecollection 2021abstractpurpose analyze etiology clinical characteristics complications treatments outcomes patients intermediate uveitis examined uveitis referral center bogot colombiapatients methods conducted retrospective descriptive study reviewed systematically clinical records patients attending uveitis referral center bogot colombia 2013 2020 data analysis included demographics etiology clinical characteristics treatment modalities bestcorrected visual acuity complications categorical variables absolute relative frequencies used continuous variables mean standard deviations calculatedresults identified 18 patients intermediate uveitis mean age disease onset 194 years sex predominance twothirds patients presented bilateral involvement mean initial bestcorrected visual acuity 019 logmar common etiology idiopathic followed undetermined tuberculosis multiple sclerosis juvenile idiopathic arthritis common characteristics insidious onset chronic course persistent duration complications found macular edema optic disk edema cataract epiretinal membrane among others corticosteroids immunosuppressive therapy common treatments mean followup time 244 months mean final bestcorrected visual acuity 012 logmarconclusion first study describing intermediate uveitis features south america context intermediate uveitis infrequent polyautoimmunity familial autoimmunity phenomena found patients may require multidisciplinary approach ophthalmologists promptly diagnose treat refer patients disease avoid common complications studies required determine disease relation polyautoimmunitypmid34188438 pmcpmc8232839 doi102147 opths309193,0.0
connecting neuroinflammation neurodegeneration multiple sclerosis oligodendrocyte precursor cells nexus disease front cell neurosci 2021 jun 21 15654284 doi 103389 fncel2021654284 ecollection 2021abstractthe pathology neurodegenerative diseases often accompanied inflammation wellknown many cells within central nervous system cns also contribute ongoing neuroinflammation can promote neurodegeneration multiple sclerosis ms inflammatory neurodegenerative disease complex interplay resident cns cells mediate myelin axonal damage communication network can vary depending subtype chronicity disease oligodendrocytes myelinating cell cns precursors oligodendrocyte precursor cells opcs often thought targets autoimmune pathology ms several animal models ms however emerging evidence opcs actively contribute inflammation directly indirectly contributes neurodegeneration discuss several contributors ms disease progression starting lesion pathology murine models amenable studying particular aspects disease review opcs can play active role promoting neuroinflammation neurodegeneration resident cns cells including microglia astrocytes neurons can impact opc function outline complex pleiotropic role s several inflammatory cytokines secreted factors classically described solely deleterious ms animal models fact many neuroprotective functions promote return homeostasis part via modulation opc function finally since ms affects patients onset disease throughout lifespan discuss impact aging opc function cns recovery becoming clear opcs simply bystander ms progression uncovering active roles play different stages disease will help uncover potential new avenues therapeutic interventionpmid34234647 pmcpmc8255483 doi103389 fncel2021654284,1.0
direct indirect costs costdriving factors tuberous sclerosis complex children adolescents caregivers multicenter cohort study background tuberous sclerosis complex tsc multisystem genetic disorder affects many organs systems characterized benign growths german multicenter study estimated diseasespecific costs costdriving factors associated various organ manifestations tsc patientsmethodsa validated threemonth retrospective questionnaire administered assess sociodemographic clinical characteristics organ manifestations direct indirect outofpocket nursing carelevel costs completed caregivers patients tsc throughout germanyresultsthe caregivers 184 patients mean age 98 53 years range 07218 years submitted questionnaires reported tsc disease manifestations included epilepsy 92 skin disorders 86 structural brain disorders 83 heart circulatory system disorders 67 kidney urinary tract disorders 53 psychiatric disorders 51 genetic variations tsc2 reported 46 patients whereas 14 reported tsc1 mean total direct health care costs eur 4949 95 confidence interval 95 ci eur 40885863 median eur 2062 per patient three months medication costs represented largest direct cost category 54 total direct costs mean eur 2658 mechanistic target rapamycin mtor inhibitors representing largest share 47 eur 2309 cost antiseizure drugs asds accounted mean eur 260 5 inpatient costs 21 eur 1027 ancillary therapy costs 8 eur 407 also important direct cost components mean nursing carelevel costs eur 1163 95 ci eur 10271314 median eur 1635 three months total indirect costs totaled mean eur 2813 95 ci eur 22213394 median eur 215 mothers eur 372 95 ci eur 193586 median eur 0 fathers multiple regression analyses revealed polytherapy two asds use mtor inhibitors independent costdriving factors total direct costs disability psychiatric disease independent costdriving factors total indirect costs well nursing carelevel costsconclusionsthis study revealed substantial direct including medication nursing carelevel indirect costs associated tsc three months highlighting spectrum organ manifestations treatment needs german healthcare settingtrial registration drks drks00016045 registered 01 march 2019 http wwwdrksde drks00016045,0.0
selfreported burden caregiver adults depression crosssectional study five western european countries background caregiving depression imposes complex health economic burden moreover paucity studies examining impact caregiving adult relatives unipolar depression cgud study assessed burden among cgud five western european eur5 countries france germany italy spain united kingdom compared caregivers adults chronic comorbidities cgod general noncaregiving noncg populationmethodsa retrospective observational study conducted using 2016 national health wellness survey nhws eur5 differences humanistic burden health status healthrelated quality life hrqol economic burden work productivity activity impairments health care resource utilization hru assessed cgud cgod respondents caregiverspecific burden caregiving responsibilities caregiver reaction assessment cra assessed caregiver groups generalized linear models used compare groups outcomes adjusting potential confoundersresultsof 77 418 survey respondents examined 1380 identified cgud 6470 cgod 69 334 noncg compared cgod noncg cgud reported significantly lower health status eg euroqol5 dimensions5 levels eq5d5l cgud 063 cgod 067 noncg 073 p 0001 hrqol eg mental component score cgud 350 cgod 378 noncg 407 p 0001 although effect sizes small d 02 minimal clinically important differences mcid apparent hrqol health status increased economicrelated burden observed work activity impairment eg absenteeism cgud 326 cgod 265 noncg 148 p 0001 hru eg healthcare provider hcp mean past 6 months cgud 105 cgod 86 noncg 68 p 0001 caregivingspecific burden associated experiencing greater lack family support cgud 29 vs cgod 28 p 001 impact finances cgud 30 vs cgod 29 p 0036 caregivers schedule cgud 31 vs cgod 30 p 0048 conclusioncaregivers persons chronic disease experience excess humanistic economic burden compared general population greater burden confronting caregiver adults depression findings illustrate farreaching burden depression patient relatives care,0.0
fiveyear realworld data fingolimod treatment#39 s effects cognitive function cognition one important parameters patient followup msalthough drug specific effect cognition ms important data show effect dmds used cognitionlongterm positive effects fingolimod physical cognitive parameters demonstrated,0.0
regret therapeutic decisions multiple sclerosis care literature review research protocol front neurol 2021 jun 21 12675520 doi 103389 fneur2021675520 ecollection 2021abstractbackground decisions based erroneous assessments may result unrealistic patient family expectations suboptimal advice incorrect treatment costly medical errors regret common emotion daily life involves counterfactual thinking considering alternative choices limited information available carerelated regret affecting healthcare professionals managing patients multiple sclerosis ms methods reviewed identified gaps literature searching combination following keywords pubmed regret decision regret physicians regret nurses expert panel neurologists nurse psychiatrist pharmacist psychometrics specialist participated study design carerelated regret will assessed behavioral battery including standardized questionnaire regret intensity scale ris10 15 new specific items six items will evaluate regret common social domains affecting individuals financial driving sportsrecreation work health confidence people another nine items will explore past recent regret experiences common situations experienced healthcare professionals caring patients ms will also assess concomitant behavioral characteristics healthcare professionals associated regret coping strategies life satisfaction mood positive social behaviors occupational burnout tolerance uncertainty planned outcomes first comprehensive standardized protocol assess carerelated regret associated behavioral factors among healthcare professionals managing ms results will allow understand ameliorate regret healthcare professionals spanish national register sl4212920 598e pmid34234734 pmcpmc8256155 doi103389 fneur2021675520,0.0
genomic functional evaluation tnfsf14 multiple sclerosis susceptibility j genet genomics 2021 may 25s16738527 21 001272 doi 101016 jjgg202103017 online ahead printabstractamong multiple sclerosis ms susceptibility genes strongest nonhuman leukocyte antigen hla signal italian population maps tnfsf14 gene encoding light glycoprotein involved dendritic cell dc maturation finemapping large italian dataset 4 198 patients ms 3 903 controls show tnfsf14 intronic snp rs1077667 primarily msassociated variant region expression quantitative trait locus eqtl analysis indicates ms risk allele significantly associated reduced tnfsf14 messenger rna levels blood cells consistent allelic imbalance rnaseq reads p 00001 ms risk allele associated reduced levels tnfsf14 gene expression p 001 blood cells 84 italian patients ms 80 healthy controls hcs interestingly patients ms lower expressors tnfsf14 compared hc p 0007 individuals homozygous ms risk allele display increased percentage lightpositive peripheral blood myeloid dcs cd11c+ p 0035 37 hcs well vitro monocytederived dcs 22 hcs p 004 findings suggest intronic variant rs1077667 alters expression tnfsf14 immune cells may play role ms pathogenesispmid34353742 doi101016 jjgg202103017,0.0
brain size reductions associated endothelin b receptor mutation cause hirschsprungs disease background etb reported regulate neurogenesis vasoregulation foetal development dysfunction known cause hscr aganglionic colonic disorder syndromic forms reported associate small heads developmental delay therefore asked cns maldevelopment general feature etb mutation investigate reviewed microct scans etb model animal sl sl rat quantitatively evaluated structural changes brain constituentsmethodseleven neonatal rats generated etb+ cross breeding sacrificed microct scans completed following 15 iodinestaining protocols scans reviewed morphological changes selected organs segmented semiautomatically postnlm filtering tbr tcc tcp ob med cer pit si col volumetric measurements made using drishti rendering software rat genotyping completed following analysis statistical comparisons organ volume organ growth rate organ volume bodyweight ratios made sl sl control groups based autosomal recessive inheritance oneway anova also performed evaluate potential dosedependent effectresultssl sl rat 1632 lower body weight 353 lower growth rate control group gross intracranial morphology preserved sl sl rats however significant volumetric reduction 2033 detected tbr similar reductions extended measurements tcc tcp ob med pit consistently lower brain selected constituent growth rates detected sl sl rat ranging 621 1151 reduction lower organ volume bodyweight ratio detected sl sl rats reflecting disproportional neural changes respect body size consistent linear relationships exist etb copies intracranial organ size growth ratesconclusionalthough etb mutant normal cns morphology significant size reductions brain constituents detected structural changes likely arise combination factors secondary dysfunctional et1 et3 etb signalling including global growth impairment hscrinduced malnutrition dysregulations neurogenesis angiogenesis cerebral vascular control changes important clinical implications autonomic dysfunction intellectual delay although human study warranted study suggested comprehensive managements required hscr patients least etb subtype,0.0
mir206 regulates th17 treg ratio osteoarthritis background present study aimed determine functional role mir206 t helper 17 th17 regulatory t treg cell differentiation development osteoarthritis oa methodspatients oa healthy controls recruited investigating association mir206 th17 treg ratio transfection experiments conducted cd4+ t cells verify mechanism mir206 balance treg th17 oa model constructed detect clinical score histopathological changes treg th17 ratio oa model induced rats verify effect mir206 inhibition th17 treg immunoregulationresultshigh expression mir206 positively correlated peripheral th17 treg imbalance patients oa interactions mir206 3 untranslated regions 3utr suppressor cytokine signaling3 socs3 fork head transcriptional factor 3 foxp3 confirmed luciferase reporter assays mir206 disturbed th17 treg balance targeting socs3 foxp3 vivo assay demonstrated antagomir directed mir206 restored th17 treg balance development oaconclusionmir206 contributed progression oa modulating th17 treg imbalance suggesting mir206 inhibition might promising therapeutic strategy treatment oa,0.0
locomotive syndrome hemodialysis patients association quality lifea crosssectional study background locomotive syndrome ls defined impairment mobility functionthis study aimed clarify ls association quality life hemodialysis patientsmethodsthis crosssectional study subjects chronic kidney disease patients undergoing maintenance hemodialysis treatment ls assessed using two physical tests twostep test standup test one selfreported test geriatric locomotive function scale25 ls two stages severity beginning decline mobility function known locomo stage 1 progression decline mobility function known locomo stage 2 used sf36 assess quality life examined relationships locomo stages chisquare test kruskalwallis test jonckheereterpstra test mantelhaenszel test used analysis multiple linear regression used model crosssectional association locomo stages component summary score sf36resultsa total 76 hemodialysis patients included number subjects locomo stage 1 stage 2 19 25 53 70 respectively four 5 subjects mobility dysfunction component summary score sf36 physical function role emotional physical component summary mental component summary significantly associated locomo stagesconclusiona high prevalence severity ls hemodialysis patients found severity associated quality life,0.0
proteomics bioinformatics reveal insights neuroinflammation acute subacute phases rat models spinal cord contusion injury abstractneuroinflammation recognized hallmark spinal cord injury sci although neuroinflammation important pathogenic factor leads secondary injuries sci neuroprotective antiinflammatory treatments remain ineffective management sci moreover molecular signatures involved pathophysiological changes occur course sci remain ambiguous current study investigated proteins pathways involved c5 spinal cord hemicontusion injury using rat model means 4d labelfree proteomic analysis furthermore two gene expression omnibus geo transcriptomic datasets western blot assays immunofluorescent staining used validate expression levels localization dysregulated proteins present study observed rat models sci associated enrichment proteins related complement coagulation cascades cholesterol metabolism lysosome pathway throughout acute subacute phases injury intriguingly current study also observed 75 genes significantly altered geo datasets including anxa1 c1qc ctsz gm2a gpnmb pycard temporal clustering analysis revealed continuously upregulated protein cluster associated immune response lipid regulation lysosome pathway myeloid cells additionally five proteins validated means western blot assays immunofluorescent staining showed proteins coexisted f4 80+ reactive microglia infiltrating macrophages conclusion proteomic data pertaining current study indicate notable proteins pathways may novel therapeutic targets treatment sci,1.0
nlrc5 potential target central nervous system disorders front immunol 2021 jun 18 12704989 doi 103389 fimmu2021704989 ecollection 2021abstractnucleotide oligomerization domainlike receptors nlrs class pattern recognition receptors participate hosts first line defense invading pathogenic microorganisms nlr family caspase recruitment domain containing 5 nlrc5 largest member nlr family shown play important role inflammatory processes angiogenesis immunity apoptosis regulating nuclear factorb type interferon inflammasome signaling pathways well expression major histocompatibility complex genes recent studies found nlrc5 also associated neuronal development central nervous system cns diseases cns infection cerebral ischemia reperfusion injury glioma multiple sclerosis epilepsy review summarizes research progress structure expression biological characteristics nlrc5 relationship cnspmid34220868 pmcpmc8250149 doi103389 fimmu2021704989,0.0
effect greylevel discretization texture feature different weighted mri images diverse disease groups plos one 2021 jun 18 16 6 e0253419 doi 101371 journalpone0253419 ecollection 2021abstractpurpose many studies mri radiomics include discretization method used analyses might indicate discretization methods used considered irrelevant goals compare three frequently used discretization methods lesion relative resampling lrr lesion absolute resampling lar absolute resampling ar applied data set along two different lesion segmentation approachesmethods analyzed effects altering bin widths bin numbers three different sampling methods using 40 texture indices tis impact evaluated brain mri studies obtained 71 patients divided three different disease groups multiple sclerosis ms n 22 ischemic stroke n 22 cancer patients n 27 two different mri acquisition protocols considered patients t2 postcontrast 3d t1weighted mri sequence elliptical manually drawn vois employed imaging series three different types graylevel discretization methods used lrr lar ar hypothesis tests done among diseased control areas compare ti values areas also correlation analyses ti values lesion volumesresults general significant differences reported results employing ar lar discretization methods found employing 38 tis introduced variation results number bin parameters altered suggesting degree direction monotonicity ti value binning parameters characteristic ti furthermore tis changing altering binning values changes correlated neither disease mri sequence found indices correlated weakly volume correlation coefficients independent diseases analyzed mr contrast several cooccurrencematrix based texture parameters show definite higher correlation employing lrr discretization method however best correlations obtained manually drawn voi hypothesis tests among disease control areas colateral hemisphere revealed ar lar discretization techniques provide suitable texture features lrr addition manually drawn segmentation gave fewer significantly different tis ellipsoid segmentations addition amount tis significant differences increasing increasing number bins decreasing bin widthsconclusion findings indicate ar discretization method may offer best texture analysis mr image assessments employing many bins large bin widths might reduce selection tis can used differential diagnosis general statistically different tis observed elliptical segmentations compared manually drawn vois texture analysis mr studies studies publications report important parameters methods related data collection corrections normalization discretization segmentationpmid34143830 doi101371 journalpone0253419,0.0
investigating acoustic correlates intelligibility gains losses slowed speech hybridization approach j speech lang pathol 2021 may 28118 doi 101044 2021_ajslp2000172 online ahead printabstractpurpose exploratory study sought identify acoustic variables explaining raterelated variation intelligibility speakers dysarthria secondary multiple sclerosis method seven speakers dysarthria due multiple sclerosis produced set harvard sentences habitual slow rates speakers selected larger corpus basis raterelated intelligibility characteristics four speakers demonstrated improved intelligibility three speakers demonstrated reduced intelligibility rate slowed speech analysis resynthesis paradigm termed hybridization used create stimuli segmental ie shortterm spectral suprasegmental variables ie sentencelevel fundamental frequency energy characteristics duration sentences produced slow rate donated individually combination habitually produced sentences online crowdsourced orthographic transcription used quantify intelligibility six hybridized sentence types original habitual slow productions results sentence duration alone contributing factor improved intelligibility associated slowed rate speakers whose intelligibility improved slowed rate showed higher intelligibility scores duration spectrum hybrids energy hybrids compared original habitual rate sentences suggesting acoustic cues contributed improved intelligibility sentences produced slowed rate energy contour characteristics also found play role intelligibility losses speakers decreased intelligibility slowed rate relative contribution speech acoustic variables intelligibility gains losses varied considerably speakers conclusions hybridization can used identify acoustic correlates intelligibility variation associated slowed rate approach elucidated speakerspecific individualized speech production adjustments slowing ratepmid34048663 doi101044 2021_ajslp2000172,0.0
molecular aspects disturbed platelet activation adp p2y 12 pathway multiple sclerosis int j mol sci 2021 jun 18 22 12 6572 doi 103390 ijms22126572abstractepidemiological studies confirm high risk ischemic events secondaryprogressive multiple sclerosis sp ms patients directly associated increased level prothrombotic activity platelets work aimed verify potential molecular abnormalities platelet p2y12 receptor expression functionality cause increased risk thromboembolism observed course ms demonstrated enhanced platelet reactivity response adenosine diphosphate adp sp ms relative controls also shown increased mrna expression p2ry12 gene platelets megakaryocytes well enhanced density receptors platelet surface postulate one reasons elevated risk ischemic events observed ms may genetically phenotypically reinforced expression platelet p2y12 receptor order analyze effect par1 protease activated receptor type 1 signaling pathway expression level p2y12 also analyzed correlation parameters p2y12 expression markers platelet activation ms induced selective par1 agonist thrombin receptor activating peptide6 trap6 identifying molecular base responsible enlarged prothrombotic activity platelets sp ms contribute implementation prevention targeted treatment reducing development cardiovascular disorders course diseasepmid34207429 doi103390 ijms22126572,0.0
obesity multiple sclerosisa multifaceted association j clin med 2021 jun 18 10 12 2689 doi 103390 jcm10122689abstractbackground given common elements pathophysiological theories try explain appearance evolution obesity multiple sclerosis association two pathologies become increasingly researched topic recent years one hand chronic demyelinating inflammation caused autoimmune cascade multiple sclerosis hand according latest research shown obesity shares inflammatory component chronic diseasesmethods authors performed independent research available literature important electronic databases pubmed google scholar embase science direct february 2021 applying exclusion criteria reviewers focused relevant articles published last 10 years respect epidemiology pathophysiologyresults data presented step forward trying elucidate intricate relationship obesity ms especially causal relationship childhood adolescent obesity ms focusing epidemiological associations observed relevant observational studies conducted recent years second part authors comment latest findings related pathophysiological mechanisms may explain correlations obesity multiple sclerosis focusing also role adipokinesconclusions based available epidemiological data obesity early life appears strongly associated higher risk ms development independent risk factors although much research done pathophysiology obesity ms possible common mechanism role adipokines studies needed order explain remains unknown relevant data found regarding association obesity disability high edss score mortality risk ms patients thus consider topic elucidated future researchpmid34207197 doi103390 jcm10122689,1.0
articulatory correlates stress pattern disturbances talkers dysarthria j speech lang hear res 2021 may 13114 doi 101044 2021_jslhr2000299 online ahead printabstractpurpose reduced stress commonly occurs talkers parkinsons disease pd whereas excessive equal stress frequently associated dysarthria talkers amyotrophic lateral sclerosis als multiple sclerosis ms study sought identify articulatory impairment patterns underlie two impaired stress patterns aimed determine talkers stress pattern disturbance different diseases als ms exhibit diseasespecific articulatory deficits method fiftyseven talkers participated study33 talkers dysarthria 24 controls talkers dysarthria grouped based medical diagnosis pd n 15 als n 10 ms n 8 participants repeated target words embedded carrier phrase kinematic data recorded using electromagnetic articulography duration displacement peak speed stiffness timetopeak speed parameter c extracted initial lower lip opening stroke target word either stressed unstressed results stress effects significant kinematic measures across groups except stiffness timetopeak speed nonsignificant als comparisons controls kinematic measures significantly differed als group pd ms groups additionally als ms showed mostly similar articulatory impairment patterns conclusions general significant stress effects observed talkers dysarthria however stressspecific betweengroup differences articulatory performance particularly displacement may explain perceptual impression disturbed stress patterns furthermore similar findings als ms suggest articulatory deficits underlying similar stress pattern disturbances diseasespecificpmid33984259 doi101044 2021_jslhr2000299,0.0
global adherence pharmacotherapeutic treatment patients multiple sclerosis summaryobjectiveto measure indirect adherence patients multiple sclerosis ms pharmacological treatments comparing medication disease concomitant treatments chronically prescribedmethodsa crosssectional descriptive november 2018 study pharmacy department spanish secondary hospital valencian community study population patients diagnosed ms different variants treated hospital dispensing drugs minimum six months time study variable evaluated percentage adherence patients medication measured ratio doses prescribed drugs dispensed considering adherent patients percentage equal higher 80resultsthe study included 86 patients pharmacy external outpatient unit average exposure time drugs 1987279 days adherence treatment multiple sclerosis 98166 rest chronic medication concomitant 928195conclusionsadherence pharmacological treatments population high patients shown greater adherence drugs dispensed pharmacy external outpatient unit possibly consider rest medication less important treat milder comorbidities pathologieskey words multiple sclerosis adherence treatment dmd hospital pharmacy primary care,0.0
case report myelin oligodendrocyte glycoprotein antibodyassociated disorder masquerading multiple sclerosis underrecognized entity front immunol 2021 jun 17 12671425 doi 103389 fimmu2021671425 ecollection 2021abstractmyelin oligodendrocyte glycoprotein mog antibodyassociated disease mogad covers wide spectrum manifestations defined presence mog seropositivity however proportion patients may overlap clinical radiological manifestations mogad multiple sclerosis ms wary entity critical ensure appropriate therapy herein present case recurrent episodes shortsegment myelitis typical multiple sclerosis later diagnosed mogad mog antibody seropositivity case along previous reports highlights increasingly recognized subgroup mogad initial clinical phenotypes suggestive ms later showing disease course therapeutic response compatible mogad given potential overlap clinical phenotypes patients ms mogad recommend mog antibody testing patients recurrent shortsegment myelitis conus medullaris involvement demonstrated steroid dependencepmid34220818 pmcpmc8249196 doi103389 fimmu2021671425,1.0
pregnancy multiple sclerosis women relapses year conception increases risk longterm disability worsening abstractbackgroundthe influence pregnancy longterm disability multiple sclerosis ms still controversialobjectiveto assess risk longterm disability worsening pregnancy ms women compared propensityscore ps matched group ms women without pregnancymethodsin setting italian pregnancy dataset ms patients pregnancy group pg without pregnancy control group cg recruited time disability worsening expanded disability status scale edss assessed multivariable cox regression modelresultsthe psmatching retained 230 pg 102 cg patients followup 65 + 31years disability worsening occurred 87 262 women multivariable analysis disability worsening associated pregnancy women relapses year conception adjusted hazard ratio ahr 174 95 confidence interval ci 106284 p 0027 higher edss ahr 139 95 ci 112174 p 0003 younger age ahr 095 95 ci 091099 p 0022 shorter dmd exposure followup p 0008 conclusionpregnancy ms women relapses year conception increases risk longterm disability worsening findings underscore importance counselling ms women facing pregnancy planned period clinical stability favouring treatment optimization patients recent disease activity,0.0
modulation lanosterol synthase drives 24 25epoxysterol synthesis oligodendrocyte formation cell chem biol 2021 feb 16s24519456 21 000519 doi 101016 jchembiol202101025 online ahead printabstractsmall molecules promote formation new myelinating oligodendrocytes oligodendrocyte progenitor cells opcs potential therapeutics demyelinating diseases recently established inhibition specific cholesterol biosynthesis enzymes resulting accumulation 8 9unsaturated sterols unifying mechanism many molecules act identify potent sterol enhancers oligodendrocyte formation synthesized collection 8 9unsaturated sterol derivatives found 24 25epoxylanosterol potently promoted oligodendrocyte formation opcs 24 25epoxylanosterol metabolized 24 25epoxycholesterol via epoxycholesterol shunt pathway increasing flux epoxycholesterol shunt using genetic manipulation smallmolecule inhibition lanosterol synthase lss increased endogenous 24 25epoxycholesterol levels opc differentiation notably exogenously supplied 24 25epoxycholesterol promoted oligodendrocyte formation despite lacking 8 9unsaturation work highlights epoxycholesterol shunt usage controlled inhibitors lss target promote oligodendrocyte formation additionally sterols beyond 8 9unsaturated sterols including 24 25epoxycholesterol drive oligodendrocyte formationpmid33636107 doi101016 jchembiol202101025,1.0
characterization multiple sclerosis neuroinflammation neurodegeneration relaxation diffusion basis spectrum imaging abstractbackgroundadvanced magnetic resonance imaging mri methods can provide specific information various microstructural tissue changes multiple sclerosis ms brain quantitative measurement t1 t2 relaxation diffusion basis spectrum imaging dbsi yield metrics related pathology neuroinflammation neurodegeneration occurs across spectrum msobjectiveto use relaxation dbsi mri metrics describe measures neuroinflammation myelin axons different ms subtypesmethods103 participants 20 clinically isolated syndrome cis 33 relapsingremitting ms rrms 30 secondary progressive ms 20 primary progressive ms underwent quantitative t1 t2 dbsi conventional 3t mri whole brain normalappearing white matter lesion corpus callosum mri metrics compared across ms subtypesresultsa gradation mri metric values seen cis rrms progressive ms rrms demonstrated large oedemarelated differences progressive ms extensive abnormalities myelin axonal measuresconclusionrelaxation dbsiderived mri measures show differences ms subtypes related severity composition underlying tissue damage rrms showed oedema demyelination axonal loss compared cis progressive ms even evidence increased oedema demyelination axonal loss compared cis rrms,1.0
prevalence cooccurrence trajectories pain fatigue depression anxiety year following multiple sclerosis diagnosis abstractbackgroundpain fatigue depression anxiety common multiple sclerosis little known presence cooccurrence trajectories symptoms year multiple sclerosis ms diagnosisobjectivesto determine postdiagnosis year 1 rates pain fatigue depression anxiety 2 rates symptom cooccurrence 3 stability change symptom severitymethodsnewly diagnosed adults ms clinically isolated syndrome n 230 completed selfreport measures pain fatigue depression anxiety 1 2 3 6 9 12months ms diagnosis clinical significance defined based standardized cutoffs descriptive statistics sankey diagrams characterized rates trajectoriesresultsparticipants endorsed clinically significant symptoms point postdiagnosis year rates 509 pain 626 fatigue 474 depression 387 anxiety majority patients exhibited cooccurring symptoms213 two 191 three 174 four proportions patients clinically significant symptoms generally stable time however rates symptom development recovery revealed fluctuations individual levelconclusionspain fatigue depression anxiety prevalent newly diagnosed ms prompt screening evidencebased interventions necessary quality life optimized,0.0
cerebrospinal fluid findings 541 patients clinically isolated syndrome multiple sclerosis monocentric study front immunol 2021 jun 17 12675307 doi 103389 fimmu2021675307 ecollection 2021abstractbackground reports typical routine cerebrospinal fluid csf findings outdated owing novel reference limits rl revised diagnostic criteria multiple sclerosis ms objective assess routine csf parameters ms patients frequency pathologic findings applying novel rlmethods csf white blood cells wbc csf total protein csftp csf serum albumin quotient qalb intrathecal synthesis immunoglobulins ig m g oligoclonal igg bands ocb determined patients clinically isolated syndrome cis msresults 541 patients 54 showed csf pleocytosis wbc count 40 l csf cytology revealed lymphocytes monocytes neutrophils 99 41 9 patients csftp qalb increased 19 7 applying agecorrected rl opposed 34 26 conventional rl quantitative intrathecal igg iga igm synthesis present 65 14 21 ocb 95 patients wbc higher relapsing progressive ms predicted together monocytes conversion cis clinically definite ms intrathecal igg fraction highest secondary progressive msconclusions csf profile ms varies across disease courses bloodcsfbarrier dysfunction intrathecal iga igm synthesis less frequent novel rl appliedpmid34220821 pmcpmc8248497 doi103389 fimmu2021675307,0.0
evaluation retinal structure optic nerve function changes multiple sclerosis longitudinal study 1year followup neurol res int 2021 jun 17 20215573839 doi 101155 2021 5573839 ecollection 2021abstractbackground multiple sclerosis ms autoimmune disease characterized inflammation demyelination central nervous system often involves optic nerve even though 20 patients experience optic neuritis objective study aims compare retinal structure optic nerve function patients ms healthy controls hcs evaluate optic nerve alterations ms 1year followup analyze correlations disease duration number relapses degree disability different subtypesmethods prospective cohort study involving 58 eyes ms patients optic nerve function evaluated bestcorrected visual acuity bcva contrast sensitivity p100 latency retinal structure evaluated gcipl rnfl thickness measured optical coherence tomography oct fundus photographyresults ms group lower bcva p0001 contrast sensitivity p 0001 mean gcipl thickness p 0001 mean rnfl thickness p 0001 hc 6 12 months observations gcipl rnfl nasal quadrant ms patients decreased significantly p0007 p0004 respectively disease duration number relapses correlated delayed p100 latency r 061 p 0001 r 046 p002 gcipl rnfl spms subtype thinner rrmsconclusions retinal structure optic nerve function ms patients worse normal individuals gcipl rnfl thinning occurs 6 12 months correlate disease duration number relapses degree disabilitypmid34221503 pmcpmc8225456 doi101155 2021 5573839,1.0
predicting improvement quality life mental health 18months multiple sclerosis patients abstractbackgroundmultiple sclerosis ms chronic neurodegenerative disease can negatively affect functioning across wide spectrum domains study aims investigate development mental health quality life ms patients 18months identify predictive factorsmethod314 ms outpatients virgen macarena university hospital sevilla spain mean age 45 years 678 women average 121 years since diagnosis participated study healthrelated quality life hrqol mental health assessed 12item short form health survey sf12 general health questionnaire28 ghq28 twice 18months follow periodresultshrqol mental health significantly improved almost domains except worsening vitality mental physical hrqol improved large effect size binomial logistic regression models showed disability status expanded disability status scale predicted components hrqol age physical component hrqol sex educational level disease duration predicted mental healthconclusionsour findings confirm possibility significant largesized improvement hrqol course 18months even 12 years ms diagnosis average study showed importance sociodemographic well clinical variables predict hrqol mental health longitudinal research needed better understand impact patientsnull outcomes,0.0
algorithm using clinical data predict optimal individual glucocorticoid dosage treat multiple sclerosis relapses ther adv neurol disord 2021 jun 17 1417562864211020074 doi 101177 17562864211020074 ecollection 2021abstractbackground glucocorticoid gc pulse therapy used multiple sclerosis ms relapse treatment however gc resistance common problem considering gc dosing individual several responseinfluencing factors establishing predictive model supports clinicians estimate maximum gc dose additional therapeutic value can expected presents huge clinical needmethod established two independent retrospective cohorts ms patients first explorative cohort model generation second established validation using explorative cohort multivariate regression analysis gc dose used dependent variable serum vitamin d 25d concentration sex age edss contrast enhancement cranial magnetic resonance imaging mri immune therapy involvement optic nerve independent variables establishedresults explorative cohort 113 ms patients included 25hydroxyvitamin d 25d serum concentration presence optic neuritis independent predictors gc dose needed treat ms relapses 25d 2595 95 confidence interval ci 4740 449 p 0018 optic neuritis 204051 95 ci 58464349636 p 0006 validation multivariate linear regression model performed within second cohort predicted gc dose differ significantly dose administered clinical routine mean difference 84354 95 ci 20780839100 n 30 p 0173 conclusion model predict gc dose given clinical routine ms relapse care clinicians estimate benefit studies validate improve algorithm help implementation predictive models gc dosingpmid34211583 pmcpmc8216377 doi101177 17562864211020074,0.0
application principal component analysis characterize gait association falls multiple sclerosis sci rep 2021 jun 17 11 1 12811 doi 101038 s41598021923532abstractpeople multiple sclerosis pwms demonstrate gait impairments related falls however redundancy exists reporting gait outcomes study aimed develop msspecific model gait examine differences fallers nonfallers 122 people relapsingremitting ms 45 controls performed 3 timed upandgo trials wearing inertial sensors 21 gait parameters entered principal component analysis pca pcaderived gait domains compared ms fallers msf ms nonfallers msnf correlated cognitive clinical qualityoflife outcomes six distinct gait domains identified pace rhythm variability asymmetry anteriorposterior dynamic stability mediallateral dynamic stability explaining 7915 gait variance pwms exhibited slower pace larger variability increased mediallateral trunk motion compared controls p 005 pace asymmetry domains significantly worse ie slower asymmetrical msf msnf p 0001 p 003 respectively fear falling cognitive performance functional mobility associated slower gait p 005 study identified sixcomponent msspecific gait model demonstrating pwms particularly fallers exhibit deficits pace asymmetry findings may help reduce redundancy reporting gait outcomes inform interventions targeting specific gait domainspmid34140612 doi101038 s41598021923532,0.0
natural history relapsing remitting multiple sclerosis longlasting cohort tertiary ms centre portugal abstractbackgroundseveral diseasemodifying therapies dmts emerged last two decades treatment multiple sclerosis ms increasing use therapies enhanced need study impact longterm disease progression natural history ms study aimed characterize portuguese ms patient cohort concerns natural history disease exploring differences throughout 3 decadesmethodslongitudinal retrospective noninterventional study patients aged 18 years old confirmed diagnosis relapsingremitting ms rrms included biodemographic clinical characteristics ms diagnosis patient followup relapses treatment exams assessed compared according first appointment date throughout 10year spans 19871996 19972006 20072016 results548 patients included analysis significant differences observed decades evoked potential ep cerebrospinal fluid csf exams conducted diagnosis first less expression last decade median number relapses per year higher subgroup 0716 edss baseline last appointment higher subgroup 8796 percentage patients achieving edss 30 edss 60 increased subgroup 8796 additionally time diagnosis first treatment significantly lower patients recent decade greater percentage patients compared two subgroups last appointment second line dmtconclusionin general study reflects findings longitudinal studies ms progression already published literature recent years growing number effective dmts along earlier disease detection improvements access healthcare appear positive impact patientsnull access treatment consequently disease progression additional studies increased follow time needed investigate effect treatment improvement natural history ms,1.0
macular vessel density differs multiple sclerosis neuromyelitis optica spectrum disorder optical coherence tomography angiography study plos one 2021 jun 17 16 6 e0253417 doi 101371 journalpone0253417 ecollection 2021abstractmultiple sclerosis ms neuromyelitis optica spectrum disorder nmosd inflammatory demyelinating diseases commonly manifest optic neuritis differ pathogenic mechanism although shown retinal vessels might alter ms nmosd comparative study reported study evaluated macular vessel density 40 ms patients 13 nmosd patients 20 controls using optical coherence tomography angiography vessel density superficial capillary plexus scp significantly lower eyes ms+on nmosd+on nonon eyes mson nmosdon controls density deep capillary plexus dcp significantly increased ms+on mson eyes compared healthy eyes nmosd+on nmosdon dcp remarkably differ control group significant positive correlation noted scp ganglion cell complex gcc thickness ms+on mson nmosd+on dcp significantly correlate gcc thickness increased decreased ganglion cell loss ms nmosd respectively conclusion findings suggest capillary changes ms patients secondary ganglion cells atrophy vasculopathy seems primary process nmosd patientspmid34138942 doi101371 journalpone0253417,1.0
hepato cardioprotective effects baccharis trimera less dc multiple risk factors chronic noncommunicable diseases acad bras cienc 2021 jun 16 93 3 e20200899 doi 101590 00013765202120200899 ecollection 2021abstractcardiovascular diseases associated high morbidity mortality worldwide several risk factors including dyslipidemia smoking hypertension studies evaluated isolated risk factors experimental models cardiovascular disease preclinical studies assessed associations multiple risk factors present study hypertensive wistar rats goldblatt 2k1c model received 05 cholesterol diet exposed tobacco smoke 8 weeks last 4 weeks animals treated vehicle ethanolsoluble fraction b trimera 30 100 300 mg kg simvastatin + enalapril group normotensive nondyslipidemic nonsmoking rats treated vehicle levels aspartate aminotransferase alanine aminotransferase urea creatinine hepatic fecal lipids blood pressure mesenteric arterial bed reactivity evaluated cardiac hepatic renal histopathology tecidual redox state also investigated untreated animals exhibited significant changes blood pressure lipid profile biomarkers heart liver kidney damage treatment b trimera reversed changes effects similar simvastatin + enalapril findings suggest b trimera may promising treatment cardiovascular hepatic disorders especially disorders associated multiple risk factorspmid34161513 doi101590 00013765202120200899,0.0
serum neurofilament light chain levels healthy individuals proposal cutoff values use multiple sclerosis clinical practice backgroundserum neurofilament light snfl promising marker patientnulls monitoring multiple sclerosis ms however operating reference values use clinical practice still lacking defined snfl reference cutoff values cohort healthy controls hc assessed performance multiple sclerosis ms patients well intraindividual snfl variabilitymethodswe measured snfl single molecule array simoa assay 79 hc assessing correlation age changes snfl levels evaluated shortterm followup median 67 days consecutive samples subgroup 27 participants snfl tested 23 untreated ms patients diagnostic time start therapy median 80 days considering disease activityresultsfindings confirmed correlation snfl levels age hc thus cutoff values specific age decades calculated snfl vary significantly time shortterm followup median cv 13 snfl levels ms patients higher demonstrated higher variability diagnostic time treatment start median cv 39 according cutoff values pathologic snfl levels found 57 ms patients diagnostic time 30 samples treatment start particular pathologic snfl levels found 80 samples 16 20 obtained phase disease activity total 85 samples 22 26 associated inactive disease showed snfl normal rangeconclusionthis study demonstrates overall intraindividual stability snfl values shortterm hc suggests agedependent reference cutoff values beneficial snfl implementation clinical practice,0.0
family planning argentinian women multiple sclerosis important yet seldom approached issue mult scler j exp transl clin 2021 jun 16 7 2 20552173211025312 doi 101177 20552173211025312 ecollection 2021 aprjunabstractbackground purpose study assess family planning fp among women multiple sclerosis wwms methods invited 604 wwms answer survey focused fp temporal relationship pregnancy diagnosis multiple sclerosis b history fp c childbearing desire d information family planning comparisons pregnancy pregnancy ms well planned unplanned pregnancy analyzed multivariate univariate analyses used assess impact independent variables fpresult 428 717 wwms completed survey 191 got pregnant ms diagnosis evaluated fp last pregnancy 561 patients planned pregnancy professional addressing fp 027 95ci 008092 p 003 noninjection drug treatment pregnancy 288 95ci 101821 p 0047 independent predictors unplanned pregnancy multivariate model among wwms 40 years 487 future childbearing desire young age p 0001 pdds 3 p 0018 disease duration 5 years p 002 childbearing ms diagnosis p 0001 neurologist addressing family planning p 001 significantly associated childbearing desireconclusions research highlights pregnancy remains important concern among wwmspmid34211724 pmcpmc8216353 doi101177 20552173211025312,0.0
higher framingham risk scores associated greater loss brain volume time multiple sclerosis abstractbackgroundfew studies evaluated association comorbidities associated increased vascular risk brain volume changes multiple sclerosis ms date findings consistent respect comorbidities associated lower brain volumes whether comorbidities associated increased vascular risk associated greater brain volume loss timeobjectiveswe aimed evaluate association framingham risk score frs evaluates vascular risk normalized whole brain volume msmethodswe included 98 participants ms underwent two brain mris two years apart whole brain volumes calculated participant reported comorbidities medications taken blood pressure height weight recorded calculated frs tested association frs baseline brain volume second time point using quantile regression adjusting baseline normalized brain volume age gender use diseasemodifying therapyresultsas frs increased brain volume lower enrollment 024 95ci 042 004 followup 027 95ci 045 008 adjustment age gender use disease modifying therapy higher frs remained associated lower brain volume followup 90th percentile brain volume 222 95ci 340 104 10th 50th percentilesconclusionhigher frs associated lower brain volumes persons ms baseline brain volume loss time effect pronounced persons higher brain volumes baseline suggests prevention detection effective management comorbidities associated vascular risk people ms particularly important early disease course,0.0
regulatory t cells increase rhmog stimulation nonrelapsing decrease relapsing mog antibodyassociated disease onset children front immunol 2021 jun 16 12679770 doi 103389 fimmu2021679770 ecollection 2021abstractbackground myelin oligodendrocytes glycoprotein mog antibodyassociated disease mogad represent 25 pediatric acquired demyelinating syndrome ads 40 may relapse mimicking multiple sclerosis ms recurrent neurodegenerative ads mogabs negativeaims identify mog antigenic immunological response differences mogad ms control patients relapsing versus nonrelapsing subgroups mogadmethods three groups patients selected mogad n12 among 5 relapsing mogr 7 nonrelapsing mognr ms n10 control patients n7 peripheral blood mononuclear cells pbmc collected time first demyelinating event cultured 48 h recombinant human rh mog protein 10 g ml specific stimulation without stimulation negative control t cells immunophenotypes analyzed flow cytometry cd4+ t cells t helper th cells including th1 th2 th17 analyzed intracellular staining cytokines regulatory t cells tregs foxp3+ cd45rafoxp3+ tregs subpopulation naive tregs cd45ra+foxp3int effector tregs cd45rafoxp3high nonsuppressive tregs cd45rafoxp3int proportions determinedresults mean onset age group ranging 99 138 sex ratio similar mogr mognr ms control patients analyzed oneway anova chisquare test comparing unstimulated rhmog stimulated t cells significant increase proportion th2 th17 cells observed mogad increase th17 cells significant mognr means 063 015 vs 136 043 wilcoxontest p 003 mogr cd4+ tregs significantly increased mognr means 351 07 vs 459 133 wilcoxontest p 0046 decreased mogr cd45rafoxp3+ tregs significantly decreased mogr means 237 023 vs 199 017 paired ttest p 0021 mognr mogr showed highest ratio effector tregs non suppressivetregs significantly higher mognrconclusions findings suggest cd4+ th2 th17 cells involved pathophysiology mogad children opposite response tregs rhmog mognr cd4+ tregs increased mogr cd45rafoxp3+ tregs decreased suggests probable loss tolerance toward mog autoantigen mogr may explain relapses recurrent pediatric autoimmune diseasepmid34220827 pmcpmc8243969 doi103389 fimmu2021679770,1.0
smartphonebased application selfmanagement multiple sclerosis j healthc eng 2021 jun 16 20216749951 doi 101155 2021 6749951 ecollection 2021abstractbackground multiple sclerosis ms chronic inflammation central nervous system selfmanagement necessary ms patients purpose present study develop smartphonebased application selfmanagement multiple sclerosismethods research conducted two phases first phase users requirements investigated using questionnaire participants 120 ms patients six neurologists second phase prototype application designed usability evaluated using quis questionnaireresults proposed educational content data elements application functions medication time reminder assessing severity fatigue calculating score fatigue severity scale found necessary included application finally usability application evaluated users average mean values 76 9 indicated good level user satisfactionconclusions application designed study able collect patient data facilitated consulting physicians point need expected patients quality life health status can improved using application however research required investigate efficiency effectiveness application terms reducing number visits medical centers improving selfmanagement skills ms patients quality lifepmid34221301 pmcpmc8225446 doi101155 2021 6749951,0.0
barriers motivators tobacco smoking cessation people multiple sclerosis abstractintroductionsmoking key modifiable risk factor health outcomes people multiple sclerosis ms little evidence exists whether information support needs people ms smoke met study aimed explore knowledge attitudes beliefs smoking quitting quitting support needs australian people msmethodscurrent recent smokers recruited phone interviews social media newsletters interview data analysed nvivo using framework analysisresultswe interviewed 25 people ms 20 current five recent smokers many participants little knowledge risks smoking ms progression reported perceived benefits smoking ms symptoms others perceived smoking worsening symptoms similarly quitting believed health benefits concerns withdrawal symptoms impact ms symptoms relapses common participants reported ambivalence discussing smoking clinicians wanting information support also feeling shame guilt many participants asked smoking status ms clinicians however provision evidencebased information referrals quitting support services infrequent general practitioners often found helpful supportive participants gave weight quit advice ms cliniciansconclusionour results first indicate smoking cessation needs australian people ms met findings confirmed larger sample potential investigate whether implementing routine provision brief advice ms care coordinated effort ms researchers practitioners consumer advocates behavioural intervention services may meet needs developing targeted resources training quit counsellors provide appropriate information support specific people ms may improve smoking cessation success people ms,0.0
68ganotaevans blue pet ct findings lymphangioleiomyomatosis compared 99mtcasc lymphoscintigraphy prospective study background lymphangioleiomyomatosis lam rare multisystem disease characterized cystic lung disease extrapulmonary manifestations including lymphatic system disorder objective study investigate findings 68ganotaevans blue neb pet ct lam compare 99mtcasc lymphoscintigraphymethodsten patients diagnosed lam according american thoracic society japanese respiratory society guidelines lam recruited study pet ct acquisition performed 20 40 min subcutaneous injection 68ganeb first interdigital spaces feet 03 ml 37 mbq foot subjects also underwent 99mtcantimony sulfide colloid asc lymphoscintigraphy within week comparisonresults68ganeb pet ct displayed various lymphatic system abnormalities 10 100 10 patients included pulmonary lymphatic abnormalities 10 100 10 patients enlarged lymph nodes 5 50 lymphangioleiomyomas 2 20 dilation lumbar trunk iliac lymph vessels 5 50 thoracic duct dilation 2 20 chylous effusion 1 10 pulmonary lymphatic abnormalities positive rates 68ganeb pet ct 99mtcasc lymphoscintigraphy 100 10 10 10 1 10 respectively p 0001 7 patients extrapulmonary lymphatic manifestations 68ganeb pet ct also presented information 99mtcasc lymphoscintigraphyconclusion68ganeb pet ct visualized pulmonary lymphatic abnormality displayed extrapulmonary lymphatic system disorders lam might play role diagnosis evaluation disease 68ganeb pet ct advantageous conventional 99mtcasc lymphoscintigraphy lam providing detailed information lymphatic dysfunction,0.0
change fingolimod patient profiles time descriptive analysis two noninterventional studies pangaea pangaea 20 j pers med 2021 jun 16 11 6 561 doi 103390 jpm11060561abstract 1 background fingolimod gilenya first oral treatment patients relapsingremitting multiple sclerosis rrms since approval treatment landscape changed enormously 2 methods data pangaea pangaea 20 two german realworld studies descriptively analysed possible evolution patient profiles treatment behavior prospective multicenter noninterventional longterm studies fingolimod use rrms real life data 4229 pangaea patients recruited 20112013 2441 pangaea 20 patients recruited 20152018 available baseline data included demographics rrms characteristics disease severity 3 results mean age pangaea pangaea 20 patients similar 388 vs 392 years patients pangaea 20 shorter disease duration 71 vs 82 years fewer relapses year baseline 12 vs 16 disease severity baseline estimated edss sdmt lower pangaea 20 patients compared pangaea edss difference 10 points sdmt difference 33 points 4 conclusions results hint influence changes treatment guidelines label fingolimod patients profiles time patients tended lower disease activity fingolimod initiation suggesting earlier intervention indicates increased experience using fingolimod suboptimally treated rrms patients change mindset towards early treatment optimizationpmid34208513 doi103390 jpm11060561,0.0
microstructural mri correlates cognitive impairment multiple sclerosis role deep gray matter diagnostics basel 2021 jun 16 11 6 1103 doi 103390 diagnostics11061103abstractalthough cognitive impairment ci frequently observed people multiple sclerosis pwms pathogenesis still controversial conflicting results emerged concerning role microstructural gray matter gm damage especially involving deep gm structures study aimed evaluating whether differences cortical deep gm structures apparently cognitively normal acn ci pwms 36 subjects total present using extensive set diffusion mri dmri indices conventional morphometry measures results revealed increased anisotropy restriction several deep gm structures ci compared acn pwms changes volume present areas conversely reduced anisotropy restriction values detected cortical regions mostly pericalcarine cortex precuneus combined reduced thickness superior frontal gyrus insula dmri metrics none morphometric indices correlated symbol digit modality test results suggest deep gm microstructural damage can strong anatomical substrate ci pwms might allow identifying pwms higher risk developing cipmid34208650 doi103390 diagnostics11061103,0.0
spasticity spastic dystonia static stretch reflex hypertonic muscles patients multiple sclerosis clin neurophysiol pract 2021 jun 16 6194202 doi 101016 jcnp202105002 ecollection 2021abstractobjective investigate prevalence emg patterns underlying hypertonia multiple sclerosis ms whether patterns indicate different levels spinal excitabilitymethods investigated emg activity recorded 108 hypertonic muscles 59 consecutive ms patients investigate spastic dystonia sd looked presence emg activity muscles resting position investigate dynamic stretch reflex dsr static stretch reflex ssr looked presence emg activity response manually performed passive stretch muscleresults dsr evoked 104 muscles 51 muscles dsr sole emg activity pattern corresponds classical notion spasticity predominant extensors contrast ssr detected 48 muscles predominantly flexors sd observed 28 muscles showing even distribution flexor extensor muscles flexors ssr associated larger dsr compared spasticityconclusions findings likely depend central effects flexor extensor spindle afferents homonymous spinal motor neuronssignificance improving capacity assess spinal excitability ms patientspmid34278056 pmcpmc8263531 doi101016 jcnp202105002,1.0
identification monoclonal antibodies human renal glomerular endothelial cells lupus nephritis induce endothelial interferonalpha production background pathogenesis lupus nephritis ln remains fully understood study aimed explore pathogenic roles autoantibodies human renal glomerular endothelial cells hrgec ln patientsmethodsthe serum levels antihrgec antibodies systemic lupus erythematosus sle patients without ln ln patients determined cellbased enzymelinked immunosorbent assay elisa monoclonal igg antihrgec antibodies subsequently generated ln patients binding activities monoclonal antibodies hrgec crossreactivity doublestranded dna dsdna ability activate hrgec evaluatedresultsln patients higher serum levels igg antihrgec antibodies sle patients without ln healthy controls four monoclonal igg antihrgec antibodies ln14 obtained ln1 ln2 igg3 ln3 ln4 igg1 among monoclonal antibodies ln13 crossreactive dsdna functional assays showed compared igg1 igg3 isotype controls ln3 effect hrgec enhance interleukin il 6 production ln4 enhance il8 monocyte chemoattractant protein mcp 1 production ln13 possessed ability induce interferon ifn production hrgec moreover removal dna hrgec surface dnase 1 interpose binding ln13 hrgec effects ln13 ifn induction hrgecconclusionssome igg antihrgec antibodies ln patients ability enhance endothelial proinflammatory cytokine il6 il8 mcp1 production induce dnaindependent production ifn hrgec,0.0
challenges developing conducting analysing reporting covid19 study covid19 pandemic unfolds online coautoethnographic study bmj open 2021 jun 16 11 6 e048788 doi 101136 bmjopen2021048788abstractobjectives capture complexities unique experience newly formed multidisciplinary multicentre research team developing deploying covid19 study identify lessons learntdesign coautoethnographic studysetting staff two uk academic institutions national charity two major uk hospitalsparticipants researchers clinicians academics statisticians analysts patient public involvement representatives national charitymethods sampling frame content discussed shared research team members emails meeting minutes etc standard observational dimensions reflective interviews team members data thematically analysedresults data 34 meetings 50 emails 17 march 5 august 2020 analysed analysis yielded seven themes managing stress overarching themeconclusions mutual respect flexibility genuine belief team members best can circumstances essential completing timeconsuming study requiring rapid response pandemic acknowledging managing stress shared purpose can moderate many barriers lack facetoface interactions leading effective team workingpmid34135052 doi101136 bmjopen2021048788,0.0
13th postectrims meeting review new developments presented 2020 ectrims congress ii rev neurol 2021 jun 16 72 12 433442 doi 1033588 rn72122021173abstractintroduction decade ectrims congress spain hosted postectrims meeting neurologists expertise multiple sclerosis ms meet review new developments presented ectrimsaim article published two parts summarises presentations postectrims meeting held online 16 17 october 2020development second part highlights importance gender age understanding pathology disease optimising management advances made paediatric ms neuropsychological neuroimaging point view presented turn special attention paid findings contribute personalised approach therapy choosing best treatment strategy pharmacological nonpharmacological patient similarly results related possible strategies promote remyelination addressed although major advances treatment progressive forms quantitative methods classification patients highlighted addition study also includes results potential tools assessment treatment cognitive deficits relevant aspects observed spectrum neuromyelitis optica disorders finally results papers considered breaking news ectrimsactrims detailedconclusions advances presented related knowledge paediatric ms remyelination strategies cognitive assessment mspmid34109999 doi1033588 rn72122021173,1.0
acute chronic synaptic pathology multiple sclerosis gray matter abstractobjectivesto investigate extent synaptic loss contribution gray matter gm inflammation demyelination synaptic loss multiple sclerosis ms brain tissuemethodsthis study performed two different postmortem series ms control brains including deep gm cortical gm ms brain samples specifically selected presence active demyelinating gm lesions 1 000 000 individual synapses identified counted using confocal microscopy characterized glutamatergic gabaergic synaptic counts also correlated neuronal axonal lossresultsimportant synaptic loss observed active demyelinating gm lesions 589 chronic inactive gm lesions synaptic density mildly reduced compared adjacent nonlesional gray matter nlgm 126 synaptic loss equally affected glutamatergic gabaergic synapses diffuse synaptic loss observed ms nlgm compared control gm 212 overall conclusionthis study provides evidence ms brain tissue acute synaptic damage loss active gm inflammatory demyelination synaptic reorganization chronically demyelinated gm affecting equally glutamatergic gabaergic synapses furthermore study provides strong indication widespread synaptic loss ms nlgm also independently focal gm demyelination,1.0
effect adjunctive mangosteen pericarp cognition people schizophrenia secondary analysis randomized controlled trial front psychiatry 2021 jun 15 12626486 doi 103389 fpsyt2021626486 ecollection 2021abstractbackground cognitive impairment prevalent often highly burdensome people schizophrenia aim study investigate mangosteen garcinia mangostana linn pericarp extract may effective intervention improve cognitive performance population methods secondary analysis larger randomized placebocontrolled trial investigated 24weeks intervention mangosteen pericarp extract supplementation people diagnosed schizophrenia subset n 114 participants completed cognitive outcomes follow included analysis using cogstate brief battery following cognitive outcomes assessed psychomotor function attention visual learning memory visual working subgroup analyses investigated whether baseline clinical parameters baseline cognitive functioning illness severity duration depressive symptoms moderated relationship mangosteen pericarp extract intervention change cognitive outcomes results significant betweengroup changes cognitive outcomes assessed subgroup analysis based baseline cognition clinical characteristics reveal significant betweengroup difference change conclusions mangosteen pericarp extract affect cognitive outcomes people schizophrenia investigation regarding optimal dosing strategies mangosteen interventions testing additional cognitive domains may warranted trial registration anzctrorgau identifier actrn12616000859482 registered 30 june 3 2016pmid34211410 pmcpmc8239132 doi103389 fpsyt2021626486,0.0
characteristics improvements balance control using vibrotactile biofeedback trunk sway multiple sclerosis patients j neurol sci 2021 apr 1 425117432 doi 101016 jjns2021117432 online ahead printabstractbackground aims previously determined training vibrotactile feedback vtfb trunk sway improves ms patients balance impairment posed 5 questions 1 many weeks vtfb training required obtain best shortterm carry effect coe vtfb 2 long coe last vtfb training terminates 3 benefit similar stance gait 4 position velocity based vtfb effective reducing trunk sway 5 patients subjective assessments balance control improvemethods balance control 16 ms patients measured gyroscopes lower trunk gyroscopes drove directionally active vtfb headband patients trained twice per week vtfb 4 weeks determine balance control without vtfb stopped improving thereafter weekly assessments without vtfb 4 weeks 6 months determined coes endedresults 20 improvement balance normal levels occurred vtfb short term coes improved 15 20 p 0001 medium term 14 weeks coes constant 19 p 0001 6 months improvement significant 9 improvement lateral sway equal improvement occurred angle position velocity drove vtfb subjectively balance improvements peaked 3 weeks training 32 p 005 conclusions 34 weeks vtfb training yields clinically relevant sway reductions subjective improvements ms patients stance gait coes lasted least 1 month velocitybased vtfb equally effective positionbased vtfbpmid33839367 doi101016 jjns2021117432,0.0
anticd20 treatment effectively attenuates cortical pathology rat model widespread cortical demyelination background cortical demyelination represents prominent feature multiple sclerosis ms brain especially late progressive stages recently developed new rat model reassembles critical features cortical pathology characteristic progressive types ms persons affected ms bcell depleting anticd20 therapy proved successful relapsing remitting well early progressive course ms respect reducing relapse rate number newly formed lesions however development cortical pathology can prevented least slowed still clear main goal study thus increase understanding mode action bcells bcell directed therapy cortical lesions rat modelmethodsfor purpose set two separate experiments two different induction modes bcell depletion brain tissues analyzed thoroughly using histologyresultswe observed marked reduction cortical demyelination microglial activation astrocytic reaction apoptotic cell loss anticd20 antibody treated groups time noted increased neuronal preservation compared control groups indicating favorable impact anticd20 therapyconclusionthese findings might pave way research mode action bcells therefore help improve therapeutic options progressive ms,1.0
biomedical signals machine learning amyotrophic lateral sclerosis systematic review abstractintroductionthe use machine learning ml techniques healthcare encompasses emerging concept envisages vast contributions tackling rare diseases scenario amyotrophic lateral sclerosis als involves complexities yet demystified als biomedical signals present potential biomarkers used tandem smart algorithms can useful applications within context diseasemethodsthis systematic literature review slr consists searching investigating primary studies use ml techniques biomedical signals related als following definition execution slr protocol 18 articles met inclusion exclusion quality assessment criteria answered slr research questionsdiscussionsbased results identified three classes ml applications combined biomedical signals context als diagnosis 7222 communication 2222 survival prediction 556 conclusionsdistinct algorithmic models biomedical signals reported present promising approaches regardless classes summary slr provides overview primary studies analyzed well directions construction evolution technologybased research within scope als,0.0
development validation rplcms ms method quantification ceramides human serum j chromatogr b analyt technol biomed life sci 2021 may 3 1175122734 doi 101016 jjchromb2021122734 online ahead printabstractceramides keyrole lipids involved numerous central cellular processes plethora studies demonstrated levels ceramides blood circulation related different disease states type 2 diabetes cardiovascular diseases ovarian cancer multiple sclerosis others herein rplcms ms method rapid quantification ceramides cer d181 160 cer d181 180 cer d181 240 cer d181 241 human blood serum developed validated different sample preparation strategies including sle lle quechers tested aim attain effective accurate reproducible determination ceramides serum samples intra interday accuracy found 800111 878106 respectively ceramides intra interday precision found vary 005 102 rsd 22 140 rsd respectively lower limits quantification 23 ng ml cer d181 160 cer d181 180 14 ng ml cer d181 240 cer d181 241 method evaluated accordance bioanalytical method guidelines used determination serum ceramides patients coronary artery disease evaluate utility clinical analysespmid33991953 doi101016 jjchromb2021122734,0.0
central nervous systemendogenous tlr7 tlr9 induce different immune responses effects experimental autoimmune encephalomyelitis front neurosci 2021 jun 15 15685645 doi 103389 fnins2021685645 ecollection 2021abstractinnate receptors including toll like receptors tlrs implicated pathogenesis cns inflammatory diseases multiple sclerosis ms animal model experimental autoimmune encephalomyelitis eae tlr response pathogens endogenous signals includes production immunoregulatory mediators one interferon ifn type ifn plays protective role ms eae previously shown intrathecal administration selected tlr ligands induced ifn infiltration bloodderived myeloid cells central nervous system cns suppressed eae mice now extended studies evaluate potential therapeutic role cnsendogenous tlr7 tlr9 intrathecal application imiquimod tlr7 ligand cpg oligonucleotide tlr9 ligand cns otherwise unmanipulated mice induced ifn expression greater magnitude response cpg cd45+ cells meninges identified source ifn intrathecal cpg induced infiltration monocytes neutrophils cd4+ t cells nk cells whereas imiquimod recruit bloodderived cd45+ cells cpg imiquimod beneficial effect eae given time disease onset therapeutic effect cpg eae seen mice lacking type ifn receptor mice eae treated cpg proportion monocytes significantly increased cns infiltrating cells predominantly localized spinal cord meninges demyelination significantly reduced compared nontreated mice eae findings show tlr7 tlr9 signaling induce distinct inflammatory responses cns different outcome eae point recruitment bloodderived cells ifn induction possible mechanistic links tlr9 stimulation amelioration eae protective role tlr9 signaling cns may application treatment diseases mspmid34211367 pmcpmc8241214 doi103389 fnins2021685645,1.0
infbeta treatment affects global dna methylation monocytes patients multiple sclerosis j neuroimmunol 2021 apr 7 355577563 doi 101016 jjneuroim2021577563 online ahead printabstractthe combination genetic epigenetic influences alters development complex diseases aberrant patterns dna methylation associated inflammation clinical activity ms evaluated differences global dna methylation lymphocytes monocytes patients ms compared healthy controls thirtythree patients rrms pwrms five healthy individuals included dna isolated pbmcs phenolchloroform method global methylation analyzed imprint methylated dna quantification kit observed celltypespecific dna methylation pattern showed monocyte global dna methylation significantly affected ifn treatmentpmid33853016 doi101016 jjneuroim2021577563,0.0
association retinal atrophy cortical lesions leptomeningeal enhancement multiple sclerosis 7t mri abstractbackgroundretinal atrophy multiple sclerosis ms measured optical coherence tomography oct correlates demyelinating lesions brain atrophy relationship cortical lesions cls meningeal inflammation well knownobjectivesto evaluate relationship retinal layer atrophy leptomeningeal enhancement lme cls ms visualized 7tesla 7t magnetic resonance imaging mri methodsforty participants ms underwent 7t mri brain oct partial correlation mixedeffects regression evaluated relationships mri oct findingsresultsall participants cls 32 80 participants lme postcontrast mri ganglion cell inner plexiform layer gcipl thickness correlated total cl volume r045 p001 participants lme baseline thinner macular retinal nerve fiber layer mrnfl p001 gcipl p001 atrophy various retinal layers faster certain patterns lme example mrnfl declined 1113 1974 0252 m year faster spread fillpattern lme foci baseline compared without p001 conclusionthis study associates mri findings lme cortical pathology thinning retinal layers measured oct suggesting common link meningeal inflammation cls retinal atrophy ms,1.0
altered anterior default mode network dynamics progressive multiple sclerosis abstractbackgroundmodifications brain function remain relatively unexplored progressive multiple sclerosis pms despite potential provide new insights pathophysiology disease stageobjectivesto characterize dynamics functional networks rest patients pms relation clinical disabilitymethodsthirtytwo patients pms underwent clinical cognitive assessment dynamic properties functional networks retrieved transient brain activity obtained patients 25 healthy controls hcs sixteen hcs 19 patients underwent 1year followup fu clinical imaging assessment differences dynamic metrics groups longitudinal changes correlation clinical disability exploredresultspms patients compared hcs showed reduced dynamic functional activation anterior default mode network admn decrease oppositesigned coactivation executive control network ecn baseline fu processing speed visuospatial memory negatively correlated admn dynamic activity anticouplings admn auditory sensorymotor network temporalpole amygdala salience networks differently associated separate cognitive domainsconclusionpatients pms presented altered admn functional recruitment anticorrelation ecn admn dynamic functional activity interaction networks explained cognitive disability,0.0
high antibody levels human herpesvirus6a interact lifestyle factors multiple sclerosis development abstractbackgroundinfection human herpesvirus 6a hhv6a suggested increase multiple sclerosis ms risk however potential interactions hhv6a environmental lifestyle risk factors ms previously studiedmethodswe used two swedish populationbased casecontrol studies comprising 5993 cases 5995 controls using logistic regression models subjects different hhv6a antibody levels environmental exposures lifestyle habits compared regarding ms risk calculating odds ratios ors 95 confidence intervals cis potential interactions high hhv6a antibody levels common environmental exposures lifestyle factors evaluated additive scaleresultshigh hhv6a antibody levels associated increased risk developing ms or15 95 ci1416 regarding ms risk significant interactions observed high hhv6a antibody levels smoking attributable proportion ap 02 95 ci0103 low ultraviolet radiation uvr exposure ap03 95 ci0104 low vitamin d levels ap03 95 ci0006 conclusionhigh hhv6a antibody levels associated increased ms risk act synergistically common environmental lifestyle risk factors ms research needed investigate potential mechanisms underlying interactions presented study,0.0
potential risk disease modifying therapies neoplasm development coadjutant factors multiple sclerosis outpatients sci rep 2021 jun 15 11 1 12533 doi 101038 s4159802191912xabstractneoplasm development multiple sclerosis ms patients treated diseasemodifying therapies dmts widely discussed aim work determine neoplasm frequency relationship prescription pattern dmts influence patients baseline characteristics data 250 ms outpatients collected period 19812019 medical records neurology service hupm hospital universitario puerta del mar southern spainand analysed using cox models neoplasm prevalence 24 mainly located skin cancer prevalence expected ms 68 latency period ms onset neoplasm diagnosis 104 69 years median 930 09305 observation period ifn 704 patients glatiramer acetate 304 natalizumab 168 fingolimod 248 dimethyl fumarate 240 alemtuzumab 60 teriflunomide 48 administered monotherapy change pattern step therapy significantly different cancer patients vs unaffected individuals p 0011 294 receive dmts p 0000 extended cox model smoking hr 3938 ci 95 139211140 p 0010 female hr 2006 10703760 p 0030 age ms diagnosis agedg hr 1036 10121061 p 0004 risk factors neoplasm development secondary progressive ms spms phenotype hr 0179 00420764 p 0020 treatmenttime ifn hr 0923 08730977 p 0006 dmf hr 0725 05071036 p 0077 protective factors tobacco ifn lost negative positive influence survival time increased cox ph model tobacco agedg interaction risk factor cancer hr 1099 10011208 p 0049 followed flm treatmenttime hr 1219 09791517 conclusion smoking female sex agedg risk factors spms ifn treatmenttime protective factors neoplasm development smoking agedg interaction main cancer risk factorpmid34131191 doi101038 s4159802191912x,0.0
current controversies medical cannabis recent developments human clinical applications potential therapeutics neuropharmacology 2021 apr 30108586 doi 101016 jneuropharm2021108586 online ahead printabstractknowledge therapeutic potential medical cannabis greatly improved past decade everincreasing range developments human clinical applications growing body scientific evidence supports use medical cannabis products therapeutic indications whilst others evidence base remains disputed narrative review incorporate areas current evidence base substantial intractable childhood epilepsy multiple sclerosis well areas evidence still controversial ptsd anxiety provide highlevel summary current developments using findings recent major reviews well real world evidence rwe including global database registries patient reported outcomes pros one hand strongest empirical data supports use cannabisbased medicinal products cbmps conditions relatively small patient numbers yet hand conditions highest patient numbers present often debatable clinical evidence good rwe incorporating pros 1000s patients discord pros respective strength evidence randomised controlled trials rcts highlights urgent need research scientific literature examining efficacy medical cannabis many conditions still developing whilst large numbers patients globally successfully using medical cannabis treat broad range conditions conclude importance systematically developing rwe databases supplement rcts bridge current evidence gapspmid33940011 doi101016 jneuropharm2021108586,0.0
microglia rage exacerbates progression neurodegeneration within sod1g93a murine model amyotrophic lateral sclerosis sexdependent manner background burgeoning evidence highlights seminal roles microglia pathogenesis neurodegenerative diseases including amyotrophic lateral sclerosis als receptor advanced glycation end products rage binds ligands relevant als accumulate diseased spinal cord rage previously implicated progression als pathologymethodswe generated novel mouse model temporally delete ager microglia murine sod1g93a model als microglia ager deficient sod1g93a mice controls examined changes survival motor function gliosis motor neuron numbers transcriptomic analyses lumbar spinal cord furthermore examined bulkrnasequencing transcriptomic analyses human als cervical spinal cordresultstranscriptomic analysis human cervical spinal cord reveals range ager expression als patients negatively correlated age disease onset death tracheostomy degree ager expression related differential expression pathways involved extracellular matrix lipid metabolism intercellular communication microglia display increased rage immunoreactivity spinal cords high ager expressing patients sod1g93a murine model als vs respective controls demonstrate microglia ager deletion age symptomatic onset day 90 sod1g93a mice extends survival male female mice critically many pathways identified human als patients accompanied increased ager expression significantly ameliorated microglia ager deletion male sod1g93a miceconclusionsour results indicate microglia rage disrupts communications cell types including astrocytes neurons intercellular communication pathways divert microglia homeostatic inflammatory tissueinjurious program totality microglia rage contributes progression sod1g93a murine pathology male mice may relevant human disease,0.0
differential binding autoantibodies mog isoforms inflammatory demyelinating diseases neurol neuroimmunol neuroinflamm 2021 jun 15 8 5 e1027 doi 101212 nxi0000000000001027 print 2021 julabstractobjective analyze serum immunoglobulin g igg antibodies major isoforms myelin oligodendrocyte glycoprotein mogalpha 13 beta 13 patients inflammatory demyelinating diseasesmethods retrospective casecontrol study using 378 serum samples patients multiple sclerosis ms patients nonms demyelinating disease healthy controls mog alpha1igg positive n 202 negative serostatus n 176 samples analyzed reactivity human mouse rat mog isoforms without mutations extracellular mog ig domain mogecigd soluble mogecigd myelin multiple species using live cellbased tissue immunofluorescence assays elisaresults strongest igg reactivities directed longest mog isoforms alpha1 currently used standard test mogigg beta1 whereas isoforms less frequently recognized using principal component analysis identified 3 different binding patterns associated nonms disease 1 isolated reactivity mogalpha1 beta1 n 73 2 binding mogalpha1 beta1 least one alpha beta isoform n 64 3 reactivity 6 mog isoforms n 65 remaining samples negative n 176 mogigg mog isoform binding patterns associated nonms demyelinating disease differences clinical phenotypes disease course 3 mog isoform patterns distinct immunologic characteristics differential binding soluble mogecigd sensitivity mog mutations binding human mog elisaconclusions novel finding differential mog isoform binding patterns inform future studies refinement mogigg assays pathophysiologic role mogiggpmid34131067 doi101212 nxi0000000000001027,1.0
antipsychotic drugs counteract autophagy mitophagy multiple sclerosis proc natl acad sci u s 2021 jun 15 118 24 e2020078118 doi 101073 pnas2020078118abstractmultiple sclerosis ms neuroinflammatory neurodegenerative disease characterized myelin damage followed axonal ultimately neuronal loss etiology physiopathology ms still elusive fully effective therapy yet available investigated role ms autophagy physiologically controlled intracellular pathway regulating degradation cellular components mitophagy specific form autophagy removes dysfunctional mitochondria found levels autophagy mitophagy markers significantly increased biofluids ms patients active phase disease indicating activation processes keeping idea vitro vivo ms models induced proinflammatory cytokines lysolecithin cuprizone associated strongly impaired mitochondrial activity inducing lactic acid metabolism prompting increase autophagic flux mitophagy multiple structurally mechanistically unrelated inhibitors autophagy improved myelin production normalized axonal myelination two inhibitors widely used antipsychotic drugs haloperidol clozapine also significantly improved cuprizoneinduced motor impairment data suggest autophagy causal role ms inhibition strongly attenuates behavioral signs experimental model disease therefore haloperidol clozapine may represent additional therapeutic tools mspmid34099564 doi101073 pnas2020078118,1.0
updates genetics systemic sclerosis abstractsystemic sclerosis ssc complex disease interaction genetic environmental factors plays important role development pathogenesis number genetic studies including candidate gene analysis genomewide association study found associated genetic variants mainly localized noncoding regions expression quantitative trait locus influence corresponding gene expression gene variants identified risk ssc susceptibility include associated innate immunity adaptive immune response cell death sscassociated genes involved fibrotic process vascular homeostasis human leukocyte antigen class ii genes associated sscrelated autoantibodies rather ssc since pathways associated genotype phenotype still poorly understood investigations using multiomics technologies necessary characterize complex molecular architecture ssc identify biomarkers useful predict future outcomes treatment responses discover effective drug targets,0.0
chemoproteomic profiling covalent xpo1 inhibitors assess target engagement selectivity chembiochem 2021 apr 22 doi 101002 cbic202100038 online ahead printabstractselinexor covalent xpo1 inhibitor approved usa combination dexamethasone pentarefractory multiple myeloma additional xpo1 covalent inhibitors currently clinical trials multiple diseases including hematologic malignancies solid tumor malignancies glioblastoma multiforme gbm amyotrophic lateral sclerosis als important measure target engagement selectivity covalent inhibitors understand degree engagement needed efficacy avoiding mechanismbased offtarget toxicity herein report clickable probes based xpo1 inhibitors selinexor eltanexor labeling xpo1 live cells assess target engagement selectivity used mass spectrometrybased chemoproteomic workflows profile proteomewide selectivity selinexor eltanexor show highly selective xpo1 thermal profiling analysis selinexor offers orthogonal approach measure xpo1 engagement live cells believe probes assays will serve useful tools interrogate biology xpo1 inhibition cellular vivo systemspmid33887086 doi101002 cbic202100038,0.0
treatment nonspecific hdac inhibitors administered disease onset delay evolution mouse model progressive multiple sclerosis neuroscience 2021 apr 13s03064522 21 001858 doi 101016 jneuroscience202104002 online ahead printabstractdrugs able efficiently counteract progression multiple sclerosis ms still unmet need several lines evidence indicate histone deacetylase inhibitors hdaci clinicallyavailable epigenetic drugs might repurposed immunosuppression ms therapy studied effects hdaci disease evolution myelin oligodendrocyte glycoprotein mog immunized nod mice experimental model progressive experimental autoimmune encephalomyelitis peae obtain data potential clinical relevance hdaci panobinostat givinostat entinostat administered orally adopting daily treatment protocol disease onset report 3 drugs efficiently reduced vitro lymphocyte proliferation dosedependent manner notably however none drugs delayed evolution peae reduced lethality nod mice striking contrast however lymphocyte proliferation response mog well th1 th17 spinal cord infiltrates significantly lower animals exposed hdaci compared receiving vehicle put clinical context first time data cast doubt relevance hdaci treatment progressive ms pms also findings indicate akin pms neuropathogensis peae nod mice becomes independent autoimmunity thereby corroborating relevance model experimental pms researchpmid33862148 doi101016 jneuroscience202104002,1.0
differential association cortical subcortical spinal cord damage multiple sclerosis disability milestones multiparametric mri study abstractbackgroundin multiple sclerosis ms cortical subcortical infratentorial structural damage may differential contribution clinical disability according disease phasespurposeto determine relative contributions cortical deep d grey matter gm cerebellar cervical cord damage ms disability milestonesmethodsmulticentre 3t brain cervical cord t2 threedimensional 3d t1weighted images acquired 198 ms patients 139 relapsingremitting rr ms 59 progressive p ms 67 healthy controls brain cord lesion burden cortical thickness cth dgm cerebellar volumetry cord crosssectional area csa quantified random forest analyses identified predictors expanded disability status scale edss disability milestones edss 30 40 60 resultsms patients widespread atrophy investigated compartments versus controls prange 0001005 informative determinants edss 30 cord csa brain lesion volume frontal cth thalamic cerebellar atrophy outofbag oob accuracy 084 prange 0001005 edss 40 mainly predicted cerebellar cord atrophy frontal sensorimotor cth cord lesion number oob accuracy 084 prange 0001004 cervical cord csa p 0001 cord lesion number p 0003 predicted edss 60 oob accuracy 077 conclusionbrain lesion burden cortical thalamic atrophy main determinants edss 30 40 cord damage played major contribution edss 60,0.0
discovery potent selective nonzinc binding autotaxin inhibitor bio32546 acs med chem lett 2021 jun 14 12 7 11241129 doi 101021 acsmedchemlett1c00211 ecollection 2021 jul 8abstractautotaxin atx lysophospholipase d main enzyme responsible generating lpa body fluids although atx isolated conditioned medium melanoma cells later discovered play critical role vascular neuronal development atx also implicated primary brain tumor fibrosis rheumatoid arthritis well neurological diseases multiple sclerosis alzheimers disease neuropathic pain atx lpa levels increased upon neuronal injury selective atx inhibitor provide new approach treat neuropathic pain herein describe discovery novel series nonzinc binding reversible atx inhibitors particularly potent selective orally bioavailable brainpenetrable tool compound bio32546 well synthesis xray cocrystal structure pharmacokinetics vivo efficacypmid34267882 pmcpmc8274069 doi101021 acsmedchemlett1c00211,0.0
use wristworn accelerometers quantify bilateral upper limb activity asymmetry freeliving conditions people multiple sclerosis abstractbackground although upper limb ul dysfunctions quite common among people multiple sclerosis pwms scarcity information actual ul usage freeliving conditions aim present study quantitatively assess realworldnull activity time intensity possible asymmetry use among dominant nondominant uls pwmsmethods twentyeight pwms 20 women 8 men average edss 43 28 age sexmatched unaffected individuals required wear triaxial accelerometer wrist 24h day 2 weekdays raw accelerations processed calculate parameters associated time intensity use ul engaged uni bilateral activitiesresults 2day monitoring period pwms characterized significantly lower overall activity used dominant limb significantly longer time performing bilateral activities dominant limb expressed movements superior intensity proportion higher observed unaffected individualsconclusion instrumental monitoring ul activity two wristworn sensors may represent effective tool assessing contribution limb uni bilateral movements data can employed monitor progression ul dysfunctions effectiveness pharmacologic rehabilitative treatments,0.0
brain motion ii study study protocol randomized controlled trial aerobic exercise intervention older adults increased risk dementia background remains effective intervention capable reversing cases dementia current research focused prevention addressing risk factors shared cardiovascular disease dementia eg hypertension cognitive functional behavioural symptoms dementia manifest promising preventive treatment exercise study describes methods randomized controlled trial rct assesses effects aerobic exercise behavioural support interventions older adults increased risk dementia due genetic cardiovascular risk factors specific aims determine effect aerobic exercise cognitive performance explore biological mechanisms influence cognitive performance exercise training determine changes cerebrovascular physiology function persist 1 year 6month aerobic exercise intervention followed 1year behavioural support programme 18 months methodswe will recruit 264 participants aged 5080 years elevated risk dementia participants will randomly allocated one four treatment arms 1 aerobic exercise health behaviour support 2 aerobic exercise health behaviour support 3 stretchingtoning health behaviour support 4 stretchingtoning health behaviour support aerobic exercise intervention will consist three supervised walking jogging sessions per week 6 months whereas stretchingtoning control intervention will consist three supervised stretchingtoning sessions per week also 6 months following exercise interventions participants will receive either 1 year ongoing telephone behavioural support telephone support primary aim determine independent effect aerobic exercise cognitive composite score participants allocated intervention compared participants allocated stretchingtoning group secondary aims examine effects aerobic exercise number secondary outcomes determine whether aerobic exerciserelated changes persist 1year behavioural support programme 18 months discussionthis study will address knowledge gaps regarding underlying mechanisms procognitive effects exercise examining potential mediating factors including cerebrovascular physiological neuroimaging sleep genetic factors will provide novel biologic evidence aerobic exercise can prevent declines cognition ageingtrial registrationclinicaltrialsgov nct03035851 registered 30 january 2017,0.0
pulmonary function respiratory muscle strength patients multiple sclerosis mult scler int 2021 jun 14 20215532776 doi 101155 2021 5532776 ecollection 2021abstractbackground patients multiple sclerosis ms decline muscle strength physical capacity due demyelination axonal loss central nervous system patients advanced ms later stage disease also respiratory impairment may occur degree pulmonary dysfunction earlier stages ms thoroughly described therefore primary aims study describe pulmonary function respiratory muscle strength patients moderate disease course identify associations respiratory muscle strength functional capacitymethods sample 48 patients diagnosis ms mean age 56 11 years studied using descriptive crosssectional design patients disease duration 24 11 years median expanded disability status scale edss score 45 interquartile range 4065 pulmonary function assessed spirometry respiratory muscle strength peak cough flow peripheral oxygen saturation subjective breathing coughing ability physical capacity measured using 6mwt evaluatedresults patients normal pulmonary function significant abnormalities dynamic spirometry vital capacity 103 16 predicted forced expiratory volume 1 second 95 15 predicted peak expiratory flow rate 89 17 predicted lower limit normal respiratory muscle strength determined maximal inspiratory mip expiratory mep static pressures normal large differences individuals mip ranged 26 143 cmh2o 98 31 predicted mep values ranged 43 166 cmh2o 104 29 predicted two patients values lower limit normal significant positive associations mip well mep found several pulmonary function variables significant negative association found edss score mep r 0312 p 0031 mean peak cough flow 389 70 l min comparable values reported healthy adults patients experience severely decreased ability take deep breaths cough moderate correlation mep physical capacity assessed 6mwt r 0399 p 0010 peak expiratory flow pef 6mwt r 0311 p 0048 conclusion respiratory muscle strength pulmonary function assessed spirometry peak cough flow normal patients mild moderate ms however large individual differences demonstrating low respiratory muscle strength patients significant associations mep functional capacity mep disease severity found indicating patients impaired respiratory muscle strength lower functional capacity severe diseasepmid34221507 pmcpmc8219426 doi101155 2021 5532776,1.0
realworld discontinuation rate teriflunomide dimethyl fumarate multiple sclerosis mult scler j exp transl clin 2021 jun 14 7 2 20552173211022027 doi 101177 20552173211022027 ecollection 2021 aprjunabstractbackground patients ms medication switches increase risk disease reactivationobjective compare discontinuation rates due treatment failure side effects teriflunomide dimethyl fumarate investigate clinical variables affecting discontinuation ratesmethods patients received teriflunomide dimethyl fumarate haukeland university hospital 2013 2018 identified clinical demographic variables extracted norwegian ms registry causespecific cox regression models estimated rate discontinuation due treatment failure side effectsresults included 354 patients treated either dimethyl fumarate n 185 teriflunomide n 169 found 38 lower risk discontinuation treatment failure patients using dimethyl fumarate compared teriflunomide p 005 treatmentnaive subgroup n 183 found 38 reduced risk discontinuation reason among patients using dimethyl fumarate p 005 significant difference treatment groups discontinuation rate due side effects although patients reported side effects treated dimethyl fumarateconclusion findings suggests dimethyl fumarate lower risk discontinuation treatment failure among treatmentexperienced treatmentnaive patientspmid34188949 pmcpmc8209840 doi101177 20552173211022027,0.0
sequential everolimus angiomyolipoma associated tuberous sclerosis complex prospective cohort study background evaluate efficacy safety health economics sequential everolimus treating angiomyolipoma aml associated tuberous sclerosis complex tsc methodsin prospective cohort study patients met inclusion criteria received standard sequential treatment according willingness patients received initial dose everolimus 10 mg oral day 3 months standard treatment group maintained 10 mg qd 12 months sequential treatment group reduced dose 5 mg qd 4th month efficacy serum everolimus concentration safety evaluated 1 3 6 9 12 months treatment primary efficacy endpoint proportion patients confirmed angiomyolipoma response least 50 reduction total volume target aml relative baselineresultsbetween june 1 2016 june 1 2017 total 53 patients included twentythree patients received standard treatment 30 patients received sequential treatment 1 3 6 9 12 months treatment proportion patients whose total target tumor volume decreased 50 baseline 391 versus 367 435 versus 567 478 versus 50 478 versus 60 478 versus 233 respectively p 005 overall response rate skin lesions two groups 404 response rates skin lesions different times similar two groups p 005 major adverse effects aes included mouth ulceration hypertriglyceridemia hypercholesterolemia menstrual disorders significant difference two groups incidence aes 3 months treatment incidence overall grade 3 4 aes 12 months treatment significantly lower sequential treatment group average direct cost two groups 12 months 15 466 11 120 respectivelyconclusionscompared standard treatment sequential treatment equally effective lower incidence adverse events lower direct cost suggesting may alternative treatment aml associated tsc,0.0
systematic review meta analysis differential attrition active control arms randomized controlled trials lifestyle interventions chronic disease background attrition major obstacle lifestyle interventions sustained mediumtolong term can significant consequences internal validity trial degree attrition differs active control arms termed differential attrition important consideration initial stages trial planningobjectivesthe primary research question study differential attrition treatment arms lifestyle interventions prevalent chronic diseasesmethodswe performed systematic review metaanalysis 23 studies involving lifestyle intervention component cohorts chronic diseases search accessed three databases scopus medline ovid web science attrition treatment arms analysed using randomeffects model examined relationship relative attrition potential moderators time final followup time first followup type disease type control type intervention length treatmentresultsthe pooled risk ratio 100 95 ci 097 103 one study fell outside range univariable association described pooled risk ration length years final followup remain multivariable modelconclusionsultimately found evidence differential attrition mediumtolong term lifestyle intervention studies chronic disease increasing confidence conducting studies minimal potential attrition biastrial registrationprospero registration number crd42018084495,0.0
effectiveness massage therapy fatigue pain patients multiple sclerosis systematic review metaanalysis mult scler j exp transl clin 2021 jun 14 7 2 20552173211022779 doi 101177 20552173211022779 ecollection 2021 aprjunabstractbackground fatigue pain prevalent symptoms multiple sclerosis ms frequent complaint ms patients reduce quality life study aimed assess effect massage therapy pain fatigue ms patientsmethod original persian databases searched included pubmed web science embase ovid scopus cochrane library sid iranedex inception november 2020 studies reported effect massage fatigue pain included two investigators extracted relevant data independently deriving analysis mean difference md standardized mean difference smd usedresult ten studies eligible acoording criteria effect massage fatigue showed significant improvement 162 95 cl 240 083 p 00001 also results systematic review showed significant reduction pain severityconclusion massage complementary nonpharmacological therapy might associated alleviating fatigue pain ms patients based current study massage intervention ms patients possible clinical value palliating pain fatigue improving quality life however matter needs significant trial studiespmid34188950 pmcpmc8209836 doi101177 20552173211022779,0.0
evaluation intel realsense t265 tracking natural human head motion sci rep 2021 jun 14 11 1 12486 doi 101038 s41598021918615abstractaccurate robust tracking natural human head motion natural environments important number applications including virtual augmented reality clinical diagnostics well basic scientific research imu provide versatile solution recording inertial data including linear acceleration angular velocity reconstructing head position difficult impossible problem can solved incorporating visual data using technique known visualinertial simultaneous localization mapping vislam recently released commercial solution intel realsense t265 uses proprietary vislam algorithm estimate linear angular position velocity performance device tracking natural human head motion natural environments yet comprehensively evaluated goldstandard methods study used wide range metrics evaluate performance t265 different walking speeds different environments indoor outdoor two goldstandard methods optical tracking system socalled perambulator overall find performance t265 relative goldstandard methods accurate slow normal walking speeds small mediumsized environments suitability device future scientific studies depends application data presented can useful making determinationpmid34127718 doi101038 s41598021918615,0.0
multiple sclerosis immune system biomarkers novel comparison glatiramer acetate interferon beta1atreated patient groups abstractbackgroundmultiple sclerosis ms chronic demyelinating disease central nervous system cns t cells b lymphocytes involved development diseasemethodsthe following biomarkers determined peripheral blood 28 patients treated glatiramer acetate ga 21 patients treated interferon beta 1a ifn il10 baff mx1 igg igg1 igg2 igg3 igg4 baseline 6 months treatment participants confirmed ms diagnosisobjectivesthe primary objective assess percentual change biomarkers 6 months since firstline treatment initiation ga ifn secondary objective explore correlations baseline biomarkers values levels resultsa positive trend observed increase il10 concentration 3033 ifn 1565 ga ifn group observed statistically significant increase baff protein concentration 299 p 0001 found mx1 protein levels change administration ga can explained different mechanisms action ga serum levels igg immunoglobulins igg1 igg4 subclasses groups patients increased thus data accordance generally accepted assumption ifn ga capable modulating b cell systemconclusionsour results suggest treatment ifn ga pronounced influence b cell system ms,1.0
genetic analysis tryptophan metabolism genes sporadic amyotrophic lateral sclerosis front immunol 2021 jun 14 12701550 doi 103389 fimmu2021701550 ecollection 2021abstractthe essential amino acid tryptophan trp initiating metabolite kynurenine pathway kp can upregulated inflammatory conditions cells neuroinflammationtriggered activation kp excessive production kp metabolite quinolinic acid common features multiple neurodegenerative diseases including amyotrophic lateral sclerosis als addition role kp genes involved trp metabolism including incorporation proteins synthesis neurotransmitter serotonin also genetically functionally linked diseases als late onset neurodegenerative disease classified familial sporadic depending presence absence family history disease heritability estimates support genetic basis als including sporadic form disease however genetic basis sporadic als sals complex presence multiple gene variants acting increase disease susceptibility complicated interaction potential environmental factors aimed determine genetic contribution 18 genes involved trp metabolism including protein synthesis serotonin synthesis kp interrogating wholegenome sequencing data 614 australian sporadic als cases five genes kp afmid ccbl1 got2 kynu haao found either novel proteinaltering variants burden rare proteinaltering variants sals cases compared controls four genes involved trp metabolism protein synthesis wars serotonin synthesis tph1 tph2 maoa also found carry novel variants gene burden variants may represent als risk factors act alter kp lead neuroinflammation findings provide evidence role trp metabolism kp neuroinflammation als disease pathobiologypmid34194442 pmcpmc8236844 doi103389 fimmu2021701550,0.0
multiple sclerosis kenya demographic clinical characteristics registry cohort mult scler j exp transl clin 2021 jun 14 7 2 20552173211022782 doi 101177 20552173211022782 ecollection 2021 aprjunabstractbackground multiple sclerosis ms leading cause nontraumatic neurological disability young adults limited literature regarding burden ms subsaharan africa ssa objective describe demographic clinical characteristics patients ms pwms presenting tertiary referral hospital nairobimethods conducted retrospective descriptive study pwms presenting aga khan university hospital nairobi 20082018results 99 cases met diagnostic criteria ms male female ratio 14 majority 687 pwms indigenous africans mean age onset 307 years mean duration symptom onset first neuroimaging 504 years 33 patients sensory symptoms onset whereas 545 vitamin d deficiency insufficiency majority 795 relapsing remitting ms rrms 566 initiated disease modifying therapy dmt 212 patients dmt noncompliant patients rrms likely initiated dmt hospital p 0001 conclusion clinical characteristics patients largely resemble ssa cohorts african american patients delay symptom onset neuroimaging also issues dmt compliancepmid34188951 pmcpmc8209835 doi101177 20552173211022782,0.0
comparison neurite orientation dispersion density imaging twocompartment spherical mean technique parameter maps multiple sclerosis front neurol 2021 jun 14 12662855 doi 103389 fneur2021662855 ecollection 2021abstractbackground neurite orientation dispersion density imaging noddi spherical mean technique smt diffusion mri methods providing metrics sensitivity similar characteristics white matter microstructure limited comparison changes noddi smt parameters due multiple sclerosis ms pathology clinical settings purpose compare groupwise differences healthy controls ms patients noddi smt metrics investigating associations disability correlations diffusion tensor imaging dti metrics methods sixty three relapsingremitting ms patients compared 28 healthy controls noddi smt metrics corresponding intracellular volume fraction vin orientation dispersion odi ode diffusivity d smt isotropic volume fraction viso noddi calculated diffusion mri data alongside dti metrics fractional anisotropy fa axial mean radial diffusivity ad md rd correlations pairs mri metrics calculated normalappearing white matter nawm associations expanded disability status scale edss controlling age gender evaluated patientcontrol differences assessed voxelbyvoxel mni space controlling age gender 5 significance level correcting multiple comparisons spatial overlap areas showing significant differences compared using dice coefficients results noddi smt show significant associations edss standardised beta coefficient 034 nawm 037 lesions noddi vin 038 031 smt ode vin lesions p 005 significant correlations nawm observed dti noddi smt metrics noddi vin smt vin strongly correlated r 072 p 005 likewise noddi odi smt ode r 080 p 005 dti noddi smt metrics detect widespread differences patients controls nawm 1257 1190 mni brain mask smt noddi vin dice overlap 042 data conclusion smt noddi detect significant differences white matter microstructure ms patients controls concurring direction changes providing consistent descriptors tissue microstructure correlate disability show alterations beyond focal damage study suggests noddi smt may play role monitoring ms clinical trials practicepmid34194382 pmcpmc8236830 doi103389 fneur2021662855,0.0
effects aspirin vitamin d3 progesterone pregnancy outcomes autoimmune recurrent spontaneous abortion model high proportions placental lymphocytes expressing dx5+ cd25+ foxp3+ cd45+ cd4+ beneficial maintain immune tolerance improve pregnancy outcomes study aimed compare evaluate therapeutic effects aspirin vitamin d3 vitd3 progesterone autoimmune recurrent spontaneous abortion rsa model autoimmune rsa mouse model constructed embryo loss rate calculated group primary mouse placental lymphocytes isolated expression dx5+ cd25+ foxp3+ cd45+ cd4+ detected flow cytometry serum levels anticardiolipin antibody aca 2gp1 cxcl6 ifn il6 measured elisa evaluate proportion th1 th2 cells autoimmune rsa significantly increased embryo loss rate improved aspirin vitd3 progesterone treatment progesterone treatment best effect among three treatments positive expression dx5+ cd25+ foxp3+ cd45+ cd4+ vitd3 progesterone groups significantly higher autoimmune rsa group expression highest progesterone treatment group plasma autoimmune rsa mice aca 2gp1 cxcl6 ifn levels significantly higher il6 level lower levels control mice changes reversed aspirin progesterone treatment conclusion aspirin vitd3 progesterone treatment improved pregnancy outcomes autoimmune rsa mice regulating th1 th2 balance cytokines progesterone best effect three treatments,0.0
epidemiology insomnia sleep duration across mental physical health shot study front psychol 2021 jun 14 12662572 doi 103389 fpsyg2021662572 ecollection 2021abstractobjective numerous epidemiological studies conducted examine prevalence comorbidities insomnia document sleep duration common limitation many studies lack use agreedupon definitions insomnia well insufficient statistical power examine comorbid mental physical disorders conditionsaim examine prevalence insomnia operationalized according formal dsm5 criteria differences mean sleep duration across wide range mental physical disorders examining men women separatelymaterials methods data stem shot study students health wellbeing study national survey college university students norway 162 512 students aged 1835 received invitation participate 50 054 students completed internetbased survey attendance rate 308 insomnia defined according diagnostic statistical manual mental disorders 5th ed criteria sleep duration calculated separately weekdays weekends selfreported mental physical disorders conditions assessed using predefined list modified fit age group pearson chisquared tests used examine prevalence insomnia across various mental physical disorders conditions men women separately loglink binomial regression analysis used calculate effectsizes adjusting ageresults prevalence insomnia sexes significantly higher across mental disorders compared healthy reference group among females prevalence insomnia ranged 613 comorbid depression adj rr 249 95 ci 240 833 comorbid schizophrenia adj rr 337 95 ci 261435 males insomnia prevalence ranged 323 comorbid autism asperger adj rr 202 95 ci 139292 742 comorbid eating disorder adj rr 451 95 ci 387527 overall prevalence insomnia also significantly higher across physical conditions compared healthy reference group although generally lower compared mental disorders females insomnia prevalence ranged 25 comorbid multiple sclerosis significant 654 comorbid chronic fatigue syndrome adj rr 266 95 ci 244289 males insomnia prevalence ranged 20 comorbid cancer diabetes significant 742 comorbid fibromyalgia adj rr 435 95 ci 296639 similar patterns observed sleep duration significantly shorter sleep duration across many physical disorders especially mental disordersconclusion insomnia short sleep duration strongly associated range different disorders conditions insomnia strongly associated mental disorders physical conditions characterized level psychological psychosomatic propertiespmid34194368 pmcpmc8236531 doi103389 fpsyg2021662572,0.0
impact covid19 pandemic athletes disabilities preparing paralympic games tokyo abstractobjectivethe main aim study assess impact covid19 pandemic athletes preparing tokyo 2021 paralympic games 1 month lockdown poland study involved 166 athletes 106 male 66 female members either polish paralympic committee polish sports association disabledstart two organizations responsible managing regulating sports played persons disabilities polandresultsathletes disabilities strongly affected pandemic resultant lockdown majority respondents reported trained home 886 whereas 602 athletes trained outdoors 12 suspended training regimens altogether 54 athletes access sport facilities athletes reduced weekly training time almost half 94 h week vs 53 h week statistically significant difference t 16261 p 0001,0.0
clinical laboratory genetic markers development presence psoriatic arthritis psoriasis patients systematic review abstracttwenty thirty percent psoriasis pso patients will develop psoriatic arthritis psa detection pso patients risk developing psa essential prevent structural damage conducted systematic search five bibliographic databases may 2020 searched studies assessing markers clinical laboratory genetic associated development presence psa pso patients study selection quality assessment included studies performed followed qualitative best evidence synthesis determine level evidence marker association concomitant developing psa pso overall 259 possible markers identified 119 studies met inclusion criteria laboratory markers related inflammation bone metabolism reached strong level evidence association prediction psa pso cxcl10 showed strong evidence positive predictive value psa pso importance timely detecting psa pso population finding bio markers contributing early detection remains high,0.0
involve research patients carers public abstractpatient public involvement research helps make relevant useful endusers involvement influences design delivery dissemination research ultimately leading better services treatments care researchers therefore keen involve patients carers public work sometimes uncertain involve confusion may arise terms used uks catchall term patient public involvement suggests single activity perhaps patient public input needed either will terms patient carer public defined used consistently fact many different contexts involvement many different kinds decisions made determine whose input will valuableclarity can help answer question however researchers clear purpose involvement often understood moral purpose improve research quality doesnt always identify needs involved learning understood purpose involvement appropriate people involve relevant experiential knowledge research projects people lived experience topic investigated patients carers members public health professionalsin article discuss involving people relevant experiential lived knowledge may contribute ineffective tokenistic involvement people likely researchers make assumptions risking missing key insights resulting outcomes offputting even harmful research participantswe conclude greater attention needs given question involve raising awareness significance experiential knowledge contextual factors determine whose input will useful will help everyone understand roles improve quality involvement will help maximise opportunities learning increasing likelihood impact helping achieve ultimate goal improved health services,0.0
effectiveness brainstem auditory evoked potentials scoring evaluating brainstem dysfunction disability among individuals multiple sclerosis j audiol 2021 mar 26111 doi 101044 2020_aja2000155 online ahead printabstractpurpose brainstem dysfunction multiple sclerosis ms often causes significant functional impairment leading disability study aims explore modified brainstem auditory evoked potential baep scores based pattern baep abnormalities relate brainstem symptoms brainstem functional system scores bfss brainstem lesions disability method fortyfive participants relapsingremitting ms 45 age gendermatched healthy controls underwent case history assessment otoscopic examination puretone audiometry baep testing also neurological examination expanded disability status scale fss scales magnetic resonance imaging carried ms participants patterns baep abnormalities categorized converted baep scores results 45 participants brainstem symptoms bfss 1 brainstem lesions magnetic resonance imaging baep abnormalities observed 756 422 622 5556 participants respectively waves v iii abnormalities common among ms participants showed significant difference control group mannwhitney u test chisquare test show significant association baep abnormalities brainstem symptoms lesions showed significant association bfss mean standard deviation baep scores ms participants 173 + 237 healthy controls showed baep scores 0 baep scores ms participants showed significant correlation bfss scores predict expanded disability status scale scores conclusion baep scores based pattern baep abnormality can valid useful measure evaluating brainstem functions predicting disability mspmid33769865 doi101044 2020_aja2000155,0.0
nextgeneration bruton#39 s tyrosine kinase inhibitor biib091 selectively potently inhibits b cell fc receptor signaling downstream functions b cells myeloid cells clin transl immunology 2021 jun 14 10 6 e1295 doi 101002 cti21295 ecollection 2021abstractobjectives brutons tyrosine kinase btk plays nonredundant signaling role downstream bcell receptor bcr b cells receptors fc region immunoglobulins fcr myeloid cells characterise biib091 novel potent selective reversible smallmolecule inhibitor btkmethods biib091 evaluated vitro vivo preclinical models phase 1 clinical trialresults vitro biib091 potently inhibited btkdependent proximal signaling distal functional responses b cells myeloid cells ic50s ranging 3 106 nm including antigen presentation t cells key mechanism action thought underlying efficacy b celltargeted therapeutics multiple sclerosis biib091 effectively sequestered tyrosine 551 kinase pocket forming longlived complexes btk t 1 2 40 min thereby preventing phosphorylation upstream kinases key differentiating feature biib091 property explains potent whole blood ic50s 87 106 nm observed stimulated b cells myeloid cells respectively vivo biib091 blocked bcell activation antibody production germinal center differentiation phase 1 healthy volunteer trial biib091 inhibited nave unswitched memory bcell activation vivo ic50 55 nm without significant impact lymphoid myeloid cell survival 14 days dosingconclusion pharmacodynamic results obtained preclinical early clinical settings support advancement biib091 phase 2 clinical trialspmid34141433 pmcpmc8204096 doi101002 cti21295,0.0
urothelial carcinoma graft kidney molecular analyses rare case report background malignancy transplantation leading cause death among kidney transplant recipients however donorderived malignancies rare report case high grade papillary urothelial carcinoma arising transplanted kidneycase presentationa 62yearold female received kidney transplantation 30 years ago presented urinary tract infection acute renal failure hydronephrosis transplant kidney anterograde nephrostogram showed large filling defect lower pole transplant kidney proximal 34 cm ureter biopsy renal pelvic mass showed high grade urothelial carcinoma underwent anterior exenteration resection transplant native kidneys bilateral pelvic lymph node dissection pathologic examination showed high grade papillary urothelial carcinoma appeared arise pelvis graft kidney involve graft ureter native urinary bladder tumor metastasized one left obturator lymph node spared two native kidneys ureters short tandem repeat str analysis confirmed tumor donor origin nextgeneration sequencing identified amplification tert loss cdkn2a cdkn2b primary tumorconclusionwhile known transplant recipients increased risk urothelial carcinoma compared general population lack welldocumented risk factors older age transplantation bk polyomavirus infection prolonged posttransplantation history dissemination tumor case shed light de novo tumorigenesis graft kidney within host microenvironment amplification telomerase reverse transcriptase tert loss cyclin dependent kinase inhibitor 2a 2b cdkn2a cdkn2b detected tumor next gene sequencing suggests may play important role case,0.0
clinical characteristics visceral involvement mortality atrisk early diffuse systemic sclerosis longitudinal analysis observational prospective multicenter us cohort background early diffuse cutaneous systemic sclerosis dcssc highest case fatality among rheumatic diseases report baseline characteristics current immunosuppressive therapies progression skin internal organ involvement mortality multicenter prospective cohort united states us americamethodswe performed longitudinal analysis participants 12 us centers april 2012 july 2020 participants early dcssc atrisk dcssc 2 years since first nonraynauds phenomenon rp symptomresultsthree hundred one patients included baseline median disease duration 12 years since rp mean modified skin score 211 units baseline 263 873 definite dcssc 38 127 classified atrisk 112 496 patients positive antirna polymerase iii antibodies median followup duration 245 months iqr 103407 months one hundred ninety 631 participants treated immunosuppressive therapy mycophenolate mofetil used baseline followup 38 classified atrisk baseline 27 71 went develop dcssc patients characterized higher baseline mean haqdi 08 versus 04 p 005 higher baseline mrss 88 versus 44 p 001 comparison remained limited cutaneous ssc overall cohort 48 participants 211 clinically significant worsening skin fibrosis mainly occurring first year followup 41 233 absolute forced vital capacity decline 10 twenty participants 66 died 18 died first 3 years followup cardiac involvement 333 gastrointestinal dysmotility 222 progressive interstitial lung disease ild 167 main causes deathconclusionthis us cohort highlights management early ssc current era demonstrating progression skin lung involvement despite immunosuppressive therapy high mortality due cardiac involvement,0.0
2021 magnimscmscnaims consensus recommendations use mri patients multiple sclerosis summarythe 2015 magnetic resonance imaging multiple sclerosis 2016 consortium multiple sclerosis centres guidelines use mri diagnosis monitoring multiple sclerosis made important step towards appropriate use mri routine clinical practice since promulgation substantial relevant advances knowledge including 2017 revisions mcdonald diagnostic criteria renewed safety concerns regarding intravenous gadoliniumbased contrast agents value spinal cord mri diagnostic prognostic monitoring purposes developments suggest changing role mri management patients multiple sclerosis 2021 revision previous guidelines mri use patients multiple sclerosis merges recommendations magnetic resonance imaging multiple sclerosis study group consortium multiple sclerosis centres north american imaging multiple sclerosis cooperative translates research findings clinical practice improve use mri diagnosis prognosis monitoring individuals multiple sclerosis recommend changes mri acquisition protocols emphasising value three dimensionalfluidattenuated inversion recovery core brain pulse sequence improve diagnostic accuracy ability identify new lesions monitor treatment effectiveness provide recommendations judicious use gadoliniumbased contrast agents specific clinical purposes additionally extend recommendations use mri patients multiple sclerosis childhood pregnancy postpartum period finally discuss promising mri approaches might deserve introduction clinical practice near future,0.0
unilateral optic neuritis associated sarscov2 infection rare complication j case rep 2021 jun 13 22e931665 doi 1012659 ajcr931665abstractbackground since outbreak sarscov2 infection extensive research conducted pulmonary implications novel disease however limited data extrapulmonary manifestations documented causes optic involvement little understood pathophysiology around presentation possible treatments prevent longterm complications describe case optic neuritis female patient concurrently infected sarscov2 given plethora evidence supporting neurological manifestations virus hypothesize association patients optic neuritis infection sarscov2 case report 21yearold woman past medical history presented blurry vision left eye optic neuritis suspected physical examination confirmed imaging optic nerve diagnostic evaluation nonsuggestive multiple sclerosis demyelinating diseases however patient found positive sarscov2 steroids remdesivir treatment started without presence respiratory symptoms patients symptoms completely resolved day 5 hospitalization discharged home without complications conclusions optic neuritis remained uncommon complication sarscov2 rather rare complication sarscov2 one clinicians cognizant due longterm implications optic neuritis furthermore pertinent consider ophthalmic involvement sarscov2 infection appropriately guide patient care pandemic prompt treatment can lead improved outcomespmid34120138 doi1012659 ajcr931665,1.0
etiology diffuse cystic lung diseases analysis 1010 consecutive cases lam clinic background differential diagnosis diffuse cystic lung disease dcld clinical challenge wish analyze distribution etiology dcld based data single lymphangioleiomyomatosis lam clinicmethodsall dcld patients lam clinic peking union medical college hospital january 2006 december 2019 analyzed information demographic clinical radiological pathological features collectedresultsa total 1010 patients dcld ct scan evaluated sum 711 704 patients diagnosed definite probable lam diagnoses included birthoggdub syndrome 46 sjogrens syndrome 38 pulmonary langerhans cell histiocytosis 14 lung tumors 3 castleman disease 2 antineutrophil cytoplasmic antibodyassociated vasculitis 2 systemic lupus erythematosus 1 marfan syndrome 1 amyloidosis 1 congenital cystic adenomatoid malformation lung 1 pleuroparenchymal fibroelastosis 1 38 patients diagnosed sjogrens syndrome 2 diagnosed lightchain deposition disease 2 diagnosed amyloidosis 1 diagnosed lymphocytic interstitial pneumonia one hundred eightynine patients 187 undiagnosed lung biopsy results available 27 patients undiagnosed dcld group provide diagnosisconclusionapproximately 70 dcld patients lam clinic lam common differential diagnoses included birthoggdub syndrome sjogrens syndrome pulmonary langerhans cell histiocytosis detailed clinical information laboratory genetic pathological investigations provide correct diagnoses patients dcld,0.0
resilience predictor quality life participants borderline personality disorder treatment background studies suggested psychotherapy improves quality life qol participants borderline personality disorder bpd however studies differential efficacy treatments qol participants bpd moreover relationship qol resilience rarely studied participants bpd objectives examine whether people bpd worse qol nonclinical population b examine whether statistically significant differences dialectical behavioural therapy dbt systems training emotional predictability problem solving stepps cognitive behavioural therapytreatment usual cbttau improvement qol c examine whether participants show clinically significant improvements qol treatment d analyse whether resilience associated qol bpd treatment e analyse whether resilience predictor qol pretreatment posttreatmentmethodthe sample comprised 403 participants n 202 participants diagnosed bpd n 201 nonclinical participants filled quality life index resilience scale beck depression inventory clinical participants received one possible treatments dbt stepps cbttau manova regression analyses performedresultsa participants diagnosed bpd statistically significant lower resilience nonclinical population b three forms psychotherapy statistically improved qol statistically significant differences dbt stepps cbttau improvement qol c participants show clinically significant improvements qol treatment d resilience associated qol treatment e resilience predictor qol treatmentconclusionit necessary assess qol resilience studies psychotherapy bpd patients,0.0
molecular cellular pathways contributing brain aging abstractaging leading risk factor several ageassociated diseases neurodegenerative diseases understanding biology aging mechanisms essential pursuit brain health regard brain aging defined gradual decrease neurophysiological functions impaired adaptive neuroplasticity dysregulation neuronal ca2+ homeostasis neuroinflammation oxidatively modified molecules organelles numerous pathways lead brain aging including increased oxidative stress inflammation disturbances energy metabolism deregulated autophagy mitochondrial dysfunction igf1 mtor ros ampk sirts p53 central modulators metabolic control connecting aging pathways lead neurodegenerative disorders also calorie restriction cr physical exercise mental activities can extend lifespan increase nervous system resistance ageassociated neurodegenerative diseases neuroprotective effect cr involves increased protection ros generation maintenance cellular ca2+ homeostasis inhibition apoptosis recent evidence modem molecular cellular methods neurobiology brain aging exhibiting significant potential brain cells adaptation aging resistance neurodegenerative disorders,1.0
probing association multiple sclerosis epstein barr virus therapeutic perspective epsteinbarr virus ebv ubiquitous human herpesvirus infects 9095 adults worldwide cohen 2000 ebv infection also one wellestablished environmental risk factors subsequent development multiple sclerosis ms causal role ebv ms supported several key immunological epidemiological studies warner ri 1981 thacker et al 2006 levin et al 2010 munger et al 2011 dobson et al 2017 arguably fulfill bradfordhill criteria causality except one experiment criterion met demonstrating antiebv agent ebv vaccine reduces incidence ms modifies progression disease established ms several promising ebv vaccines currently early phases preclinical development however will likely take several years clinical development vaccines widely available cohen 2018 van zyl et al 2019 sterilizing antiebv vaccine potential eliminate just ms also burkitt lymphoma hodgkin nonhodgkin lymphoma nasopharyngeal cancer well infectious mononucleosis rolls et al 2010 meantime may possible answer mechanistic questions concerning role ebv ms focusing antiviral drugs antiebv therapy clinically effective ms absence immunosuppression cement causal relationship ebv ms also clarify mechanistic underpinnings ms pathogenesis suggest novel therapeutic avenues future drug development,0.0
functional electrical stimulation cycling exercise afterspinal cord injury asystematic review health fitnessrelated outcomes abstractobjectivesthe objective review summarize appraise evidence functional electrical stimulation fes cycling exercise spinal cord injury sci order inform development evidencebased clinical practice guidelinesmethodspubmed cochrane central register controlled trials embase sportdiscus cinahl searched april 2021 identify fes cycling exercise intervention studies including adults sci order capture widest array evidence available outcome measure employed studies considered eligible two independent reviewers conducted study eligibility screening data extraction quality appraisal using cochranes risk bias downs black tools study designated level 1 2 3 4 study dependent study design quality appraisal scores certainty evidence outcome assessed using grade ratings high moderate low low resultsninetytwo studies met eligibility criteria comprising 999 adults sci representing age sex time since injury lesion level lesion completeness strata muscle health eg muscle mass fiber type composition significant improvements found 3 4 level 12 studies 27 32 level 34 studies grade rating high although lacking level 12 studies significant improvements also found nearly 35 level 34 studies power output aerobic fitness eg peak power oxygen uptake fes cycling test grade ratings low conclusioncurrent evidence indicates fes cycling exercise improves lowerbody muscle health adults sci may increase power output aerobic fitness evidence summarized appraised review can inform development first international evidencebased clinical practice guidelines use fes cycling exercise clinical community settings adults sciregistration review protocol crd42018108940 prospero,1.0
symptomatic eating epilepsy two novel pediatric patients review literature abstracteating epilepsy ee form reflex epilepsy seizures triggered eating rare condition high prevalence reported sri lanka ee ictal semiology includes focal seizures without secondary generalization generalized seizures cases idiopathic focal structural changes imaging present often confined temporal lobe perisylvian region hand cases support hypothesis genetic aetiology prognosis ee extremely variable due different nature underlying disorder describe two patients symptomatic eating epilepsy 13yearold boy bilateral perisylvian polymicrogyria 2yearold boy genetic cause presence structural lesions dysfunction specific cortical regions context germline genetic alteration might lead hyperexcitation fostering epileptogenesis review available literature clarify aetiopathogenesis mechanisms underlying ee improve diagnosis management rare conditions,0.0
candidate gene screening lipid deposition using combined transcriptomic proteomic data nanyang black pigs background lower selection intensities indigenous breeds chinese pig resulted obvious genetic phenotypic divergence one breed nanyang black pig renowned high lipid deposition high genetic divergence making ideal model investigate lipid position trait mechanisms pigs understanding lipid deposition pigs might improve pig meat traits future breeding promote selection progress pigs modern molecular breeding techniques transcriptome tandem mass tagbased quantitative proteome tmt based proteome analyses carried using longissimus dorsi ld tissues individual nanyang black pigs showed high levels genetic variationresultsa large population nanyang black pigs phenotyped using multiproduction trait indexes six pigs selected divided relatively high low lipid deposition groups combined transcriptomic proteomic data identified 15 candidate genes determine lipid deposition genetic divergence among fasn cat slc25a20 main causal candidate genes genes divided lipid depositionrelated genes bdh2 fasn cat dhcr24 acaca gk sqle acsl4 scd pparacentered fat metabolism regulatory factors ppara ucp3 transcription translation regulators slc25a20 pdk4 cebpa well integrin structural proteins signal transductionrelated genes egfr conclusionsthis multiomics data set provided valuable resource future analysis lipid deposition traits might improve pig meat traits future breeding promote selection progress pigs especially nanyang black pigs,0.0
targeting s100a4 niclosamide attenuates inflammatory profibrotic pathways models amyotrophic lateral sclerosis background increasing number studies evidences amyotrophic lateral sclerosis als characterized extensive alterations different cell types different regions besides cns previously reported upregulation als models gene called fibroblastspecific protein1 s100a4 recognized proinflammatory profibrotic factor since inflammation fibrosis often mutualsustaining events contribute establish hostile environment organ functions comprehension elements responsible interconnected pathways crucial disclose novel aspects involved als pathologymethodshere employed fibroblasts derived als patients harboring c9orf72 hexanucleotide repeat expansion als patients mutations known alsassociated genes downregulated s100a4 using sirna s100a4 transcriptional inhibitor niclosamide mice overexpressing human fus adopted assess effects niclosamide vivo als pathologyresultswe demonstrated s100a4 underlies impaired autophagy profibrotic phenotype characterize als fibroblasts indeed inhibition reduces inflammatory autophagic profibrotic pathways als fibroblasts interferes different markers known pathogenic disease mtor sqstm1 p62 stat3 sma nfb importantly niclosamide vivo treatment alsfus mice reduces expression s100a4 sma pdgfr spinal cord well gliosis central peripheral nervous tissues together axonal impairment displays beneficial effects muscle atrophy promoting muscle regeneration reducing fibrosisconclusionour findings show s100a4 role alsrelated mechanisms drugs niclosamide able target inflammatory fibrotic pathways represent promising pharmacological tools als,0.0
anzer propolis protective effect rabbit spinal cord ischemia reperfusion injury abstract introduction study anzer propolis can obtained eastern black sea region turkey studied effect spinal cord ischemia reperfusion injury methods total 12 healthy male new zealand white rabbits average weight 30 35 kg separated two blind randomized groups ischemia reperfusion group n6 treatment group n6 rabbit treatment group given dose 100 mg kg ethanoldissolved anzer propolis orally 1 hour surgery blood samples examined 0th hour postoperatively 24th 48th hours tissue samples taken 48th hour sacrification results statistically significant difference two groups terms postoperative tarlov scoring p0012 difference two groups terms blood levels interleukin6 il6 tumor necrosis factoralpha tnf 48th hour myeloperoxidase mpo 24th 48th hours ischemiamodified albumin ima 24th hour intercellular adhesion molecule1 icam1 total oxidant status tos 48th hour p0005 also difference two groups terms apoptotic index data obtained terminal deoxynucleotidyl transferase tdt mediated dutp nickend labelling tunel method histopathological examination p0001 transmission electron microscopic tem analysis ischemia reperfusion group generally axonmyelin separation axoplasmic dissolution myelin separation propolis treatment group normal myelin sequencing discussion study biochemical histopathological ultrastructural neurological functional examination demonstrated anzer propolis sufficient neuroprotective effect spinal cord ischemia reperfusion injury rabbits,1.0
anzer propolis protective effect rabbit spinal cord ischemia#x2f reperfusion injury abstract introduction study anzer propolis can obtained eastern black sea region turkey studied effect spinal cord ischemia reperfusion injury methods total 12 healthy male new zealand white rabbits average weight 30 35 kg separated two blind randomized groups ischemia reperfusion group n6 treatment group n6 rabbit treatment group given dose 100 mg kg ethanoldissolved anzer propolis orally 1 hour surgery blood samples examined 0th hour postoperatively 24th 48th hours tissue samples taken 48th hour sacrification results statistically significant difference two groups terms postoperative tarlov scoring p0012 difference two groups terms blood levels interleukin6 il6 tumor necrosis factoralpha tnf 48th hour myeloperoxidase mpo 24th 48th hours ischemiamodified albumin ima 24th hour intercellular adhesion molecule1 icam1 total oxidant status tos 48th hour p0005 also difference two groups terms apoptotic index data obtained terminal deoxynucleotidyl transferase tdt mediated dutp nickend labelling tunel method histopathological examination p0001 transmission electron microscopic tem analysis ischemia reperfusion group generally axonmyelin separation axoplasmic dissolution myelin separation propolis treatment group normal myelin sequencing discussion study biochemical histopathological ultrastructural neurological functional examination demonstrated anzer propolis sufficient neuroprotective effect spinal cord ischemia reperfusion injury rabbits,1.0
histone citrullination new target tumors abstractas main protein components chromatin histones play central roles gene regulation spools winding dna histones subject various modifications including phosphorylation acetylation glycosylation methylation ubiquitination citrullination affect gene transcription histone citrullination posttranscriptional modification catalyzed peptidyl arginine deiminase pad enzymes involved human carcinogenesis study highlighted functions histone citrullination physiological regulation tumors additionally histone citrullination involves forming neutrophil extracellular traps nets relationship nets tumors illustrated finally clinical application histone citrullination pad inhibitors discussed,0.0
inflammatory signaling mechanisms bipolar disorder abstractbipolar disorder decidedly heterogeneous multifactorial disease high individual societal burden patients display overt markers elevated inflammation significant evidence suggests aberrant immune signaling contributes stages disease likely explains elevated rates comorbid inflammatory illnesses seen population individual systems intensely studied targeted relative paucity attention given interconnecting role inflammatory signals therein review presents updated overview prominent pathophysiologic mechanisms bipolar disorder mitochondrial endoplasmic reticular calcium homeostasis purinergic kynurenic hormonal neurotransmitter signaling showing inflammation act powerful nexus systems several areas high degree mechanistic convergence within paradigm highlighted present promising future targets therapeutic development screening,0.0
occupational therapy addressing ability perform activities daily living among persons living chronic conditions randomised controlled pilot study able 20 background able intervention developed enhance ability perform activities daily living adl tasks among persons living chronic conditions able generic homebased individualised 8week occupational therapy intervention program developed delivered danish municipalities previous study feasibility able evaluated terms content delivery pilot study remaining feasibility aspects randomised controlled trial including trial procedures recruitment retention ii randomisation iii adherence program iv feasibility additional outcome measurements iv access information usual occupational therapy evaluatedmethodsthe study conducted danish municipality using twoarmed parallel randomised controlled design planning recruitment strategy including 20 persons living one chronic conditions experiencing problems performing adl following progression criteria used determine future fullscale randomised controlled trial feasible recruitment 50 met eligibility criteria retention 80 ii randomisation 80 accepted randomisation procedure executed planned iii adherence program 100 followed treatment protocol iv outcome measurements 80 participants delivered relevantly fully answered questionnaires v usual occupational therapy extraction needed information successful resultsdue covid19 pandemic study truncated resulting limited sufficient data answer study questions eighteen 37 eligible persons 486 recruited treated n 6 remained 100 ii 18 accepted randomisation 100 procedure effective iii able delivered adherence 100 iv 923100 participants gave relevant complete answers two three questionnaires v needed information usual occupational therapy extractable seven nine aspectsconclusionsproceeding fullscale trial recommendable however adjustments outcome measurements inclusion criteria extraction information usual occupational therapy neededtrial registrationthe study registered clinicaltrialsgov identifier nct04295837 december 5th 2019 retrospectively registered,0.0
age related gene dst represents independent prognostic factor mycn nonamplified neuroblastoma background mycn amplification age two critical prognostic factors pediatric neuroblastoma previously revealed prognosis mycn target genes however prognostic effects age related genes neuroblastoma unclearmethodsthe prognostic significance age mycn amplification determined multivariate cox regression kaplanmeier survival analysis genes differentially expressed mycn nonamplified younger neuroblastoma patients identified using therapeutically applicable research generate effective treatments target gene expression omnibus geo datasets prognostic effects age related genes alcam cacna2d3 dst epb41l4a kif1b pediatric neuroblastoma patients determined kaplanmeier survivalresultsin pediatric pancancer analysis age associated overall survival pediatric blineage acute lymphoblastic leukemia neuroblastoma wilms tumor target dataset moreover prognostic effects age neuroblastoma validated using two independent neuroblastoma cohorts furthermore age mycn amplification independent prognostic factors pediatric neuroblastoma compared mycn nonamplified older neuroblastoma patients mycn nonamplified younger neuroblastoma patients better clinical outcomes alcam cacna2d3 dst epb41l4a kif1b highly expressed mycn nonamplified younger neuroblastoma patients higher expression levels alcam cacna2d3 dst epb41l4a kif1b associated better prognosis mycn nonamplified neuroblastoma patients dst independent prognostic factor mycn nonamplified neuroblastoma patients mycn nonamplified neuroblastoma younger patients higher dst expression levels best clinical overall survivalconclusionsage related gene dst independent prognostic factor mycn nonamplified neuroblastoma mycn nonamplified younger neuroblastoma patients higher dst expression levels best clinical overall survival,0.0
ddopachrome tautomerase activates cox2 pge2 pathway astrocytes mediate inflammation following spinal cord injury background astrocytes predominant glial cell type central nervous system cns can secrete various cytokines chemokines mediating neuropathology response danger signals ddopachrome tautomerase ddt newly described cytokine close homolog macrophage migration inhibitory factor mif protein revealed share overlapping function mif ways however cellular distribution pattern mediated astrocyte neuropathological function cns remain unclearmethodsa contusion model rat spinal cord established protein levels ddt pge2 synthesisrelated proteinase assayed western blot immunohistochemistry primary astrocytes stimulated different concentrations ddt presence absence various inhibitors examine relevant signal pathways postinjury locomotor functions assessed using basso beattie bresnahan bbb locomotor scaleresultsddt inducibly expressed within astrocytes neurons rather microglia following spinal cord contusion ddt able activate cox2 pge2 signal pathway astrocytes cd74 receptor intracellular activation mitogenactivated protein kinases mapks involved regulation ddt action selective inhibitor ddt efficient attenuating ddtinduced astrocyte production pge2 following spinal cord injury contributed improvement locomotor functionsconclusioncollectively data reveal novel inflammatory activator astrocytes following spinal cord injury might beneficial development antiinflammation drug neuropathological cns,0.0
tcr repertoire diversity multiple sclerosis highdimensional bioinformatics analysis sequences brain cerebrospinal fluid peripheral blood abstractbackgroundt cells play key role pathogenesis multiple sclerosis ms chronic inflammatory demyelinating disease central nervous system cns although several studies recently investigated tcell receptor tcr repertoire cerebrospinal fluid csf ms patients highthroughput sequencing hts deep analysis repertoire similarities differences among compartments still missingmethodswe performed comprehensive bioinformatics highdimensional tcr v sequencing data published unpublished ms healthy donors hd studies evaluated repertoire polarization clone distribution shared cdr3 amino acid sequences cdr3saa across repertoires clone overlap public databases tcr similarity architecturefindingscsf repertoires showed significantly higher public clones percentage sequence similarity compared peripheral blood pb hand failed reject null hypothesis repertoire polarization csf pb one primaryprogressive ms ppms csf repertoire differed others terms tcr similarity architecture cluster analysis splits ms hdinterpretationin ms patients presence physiological barrier bloodbrain barrier impact clone prevalence distribution impacts public clones indicating csf private site reported high v sequence similarity csftcr architecture one ppms confirmed may interesting insight ms progressive inflammatory mechanisms clustering ms repertoires hd suggests disease shapes tcr v clonal profilefundingthis study partly financially supported italian multiple sclerosis foundation fism contributed ballerinidb data collection grant #2015 r02,1.0
mir243p attenuates il1induced chondrocyte injury associated osteoarthritis targeting bcl2l12 background mir243p reported involved osteoarthritis oa resembling environment however functional role underlying mechanism mir243p chondrocyte injury associated oa remains unknownmethodsthe expression mir243p determined using reverse transcription quantitative pcr analysis oa cases control patients well il1stimulated chondrocyte cell line chon001 cell viability analyzed cck8 assay apoptosis status assessed caspase3 activity detection proinflammatory cytokines tnf il18 determined using elisa assay association mir243p b cell leukemia 2like 12 bcl2l12 confirmed luciferase reporter assayresultswe first observed mir243p expression level lower oa cases control patients il1 decreased expression mir243p chondrocyte chon001 functionally overexpression mir243p significantly attenuated il1induced chondrocyte injury reflected increased cell viability decreased caspase3 activity proinflammatory cytokines tnf il18 western blot analysis showed overexpression mir243p weakened il1induced cartilage degradation reflected reduction mmp13 matrix metalloproteinase13 adamts5 disintegrin metalloproteinase thrombospondin motifs5 protein expression well markedly elevation col2a1 collagen type ii importantly bcl2l12 demonstrated target mir243p bcl2l12 knockdown imitated overexpression significantly abrogated protective effects mir243p il1induced chondrocyte injuryconclusionsin conclusion work provides important insight targeting mir243p bcl2l12 axis oa therapy,0.0
evaluation month birth neuromyelitis optica spectrum disorders nmsod multiple sclerosis ms mult scler int 2021 jun 10 20218874999 doi 101155 2021 8874999 ecollection 2021abstractintroduction multiple sclerosis ms neuromyelitis optica spectrum disorder nmo chronic immunemediated diseases central nervous system cns environmental factors month birth can trigger diseases therefore conducted study compare months birth ms nmosd patients control groupmethods crosssectional study 2345 patients ms 220 nmosd patients 2174 healthy subjects enrolled demographic information age sex month birth education three groups extracted database associations month birth ms studied binary logistic regression adjusting year birthresults reduced birth rate septemberoctober nmosd 0309 95 ci 01500636 p 0001 ms patients 0470 95 ci 03740591 p 0001 compared general population birth rate marchapril ms higher control group 1613 95 ci 13241964 p 0001 difference birth month distribution nmosd ms patients significant difference mob among different ms types foundconclusion findings showed decreasing risk nmosd ms individuals born autumn months increasing ms risk spring studies required elucidate association month birth risk ms nmosd seasonality factorspmid34221508 pmcpmc8211531 doi101155 2021 8874999,0.0
adiponectin protects obesityrelated glomerulopathy inhibiting ros nfb nlrp3 inflammation pathway background adiponectin adipocytokine plays key regulatory role glucose lipid metabolism obesity prevalence obesity led increase incidence obesityrelated glomerulopathy org study aimed identify protective role adiponectin orgmethodssmallinterfering rna sirna gene encoding adiponectin transfected podocytes oxidative stress level determined using fluorometric assay apoptosis analyzed flow cytometry expressions podocyte markers pyrin domain containing protein 3 nlrp3 inflammasomerelated proteins measured qrtpcr immunohistochemistry western blotresultspodocytes treated palmitic acid pa showed downregulated expressions podocyte markers increased apoptosis upregulated levels nlrp3 inflammasomerelated proteins increased production inflammatory cytokines il18 il1 induced activation nfb compared vehicletreated controls decreased adiponectin expression observed serum samples high fat diet hfd fed mice decreased podocin expression upregulated nlrp3 expression observed kidney samples high fat diet hfd fed mice treatment adiponectin nlrp3 inflammasome inhibitor mcc950 protected cultured podocytes podocyte apoptosis inflammation treatment adiponectin protected mouse kidney tissues decreased podocin expression upregulated nlrp3 expression knockout adiponectin gene sirna increased ros production resulting activation nlrp3 inflammasome phosphorylation nfb podocytes pyrrolidine dithiocarbamate nfb inhibitor prevented adiponectin ameliorating ffainduced podocyte injury nlrp3 activationconclusionsour study showed adiponectin ameliorated painduced podocyte injury vitro hfdinduced injury vivo via inhibiting ros nfb nlrp3 pathway data suggest potential use adiponectin prevention treatment org,0.0
echinacoside exerts antitumor activity via mir5033p tgf1 smad aixs liver cancer background echinacoside ech main active ingredient cistanches herba known therapeutic effects metastatic tumors however effects ech liver cancer still unclear study investigate effects ech aggression liver cancer cellsmethodstwo types liver cancer cells huh7 hepg2 treated different doses ech different times gradients mtt colony formation assays used determine effects ech viability huh7 hepg2 cells transwell assays flow cytometry assays used detect effects ech treatment invasion migration apoptosis cell cycle huh7 hepg2 cells western blot analysis used detect effects ech expression levels tgf1 smad3 smad7 apoptosisrelated proteins caspase3 caspase8 cyto c liver cancer cells relationship mir5033p tgf1 detected using bioinformatics analysis luciferase reporter assayresultsthe results showed ech inhibited proliferation invasion migration huh7 hepg2 cells dose timedependent manner moreover found ech caused huh7 hepg2 cell apoptosis blocking cells s phase furthermore expression mir5033p found reduced liver tumor tissues ech treatment increased expression mir5033p huh7 hepg2 cells addition found tgf1 identified potential target mir5033p ech promoted activation tgf1 smad signaling pathway increased expression levels bax bcl2 moreover ech trigger release mitochondrial cyto c cause reaction caspases gradeconclusionsthis study demonstrates ech exerts antitumor activity via mir5033p tgf1 smad aixs liver cancer provides safe effective antitumor agent liver cancer,0.0
switch diseasemodifying treatments multiple sclerosis guidelines french multiple sclerosis society sfsep abstractbackgroundtoday recommendations switching diseasemodifying treatments dmts multiple sclerosis ms objectivesto establish guidelines switching dmts msmethodsa steering committee composed seven ms experts french group recommendations multiple sclerosis france4ms defined 15 proposals proposals submitted rating group composed 48 french ms experts evaluation proposals classified appropriatenull inappropriatenull uncertainnullresultsswitching firstline therapy another firstline therapy secondline therapy done without washout period switching secondline therapy firstline therapy done without washout period fingolimod natalizumab 3 months ocrelizumab mitoxantrone disease activity occurs alemtuzumab cladribine switch secondline therapy another secondline therapy done washout period 1 month fingolimod natalizumab 3 months ocrelizumab 6 months mitoxantrone disease activity occurs alemtuzumab cladribineconclusionthis expert consensus approach provides physicians guidelines optimizing benefit risk ratio switching dmts patients ms,0.0
nutritional ecological perspectives interrelationships diet gut microbiome multiple sclerosis insights marmosets iscience 2021 jun 10 24 7 102709 doi 101016 jisci2021102709 ecollection 2021 jul 23abstractstudies experimental autoimmune encephalomyelitis eae animal model multiple sclerosis shown potential links diet components microbiome composition modulation immune responses review reanalyze discuss findings outbred marmoset eae model yogurtbased dietary supplement decreased disease frequency severity show although diet detectable effects fecal microbiome microbiome changes strongly associated eae development using ecological framework show dominant factors influencing gut microbiota marmoset sibling pair experimental time point findings emphasize challenges assigning causeandeffect relationships studies dietmicrobiomehost interactions differentiating diet effects environmental stochastic hostrelated factors advocate animal experiments designed allow causal inferences microbiotas role pathology considering complex ecological processes shape microbial communitiespmid34296070 pmcpmc8282968 doi101016 jisci2021102709,0.0
case tuberous sclerosis complex due novel splicing variant tsc2 gene zhonghua yi xue yi chuan xue za zhi 2021 jun 10 38 6 553556 doi 103760 cmajcn5113742020021100072abstractobjective explore genetic basis patient tuberous sclerosis complexmethods genomic dna extracted peripheral blood samples members family 100 unrelated healthy controls proband subjected nextgeneration sequencing candidate variant confirmed multiple ligationdependent probe amplification mlpa sanger sequencing reverse transcriptionpcr rtpcr carried determine relative mrna expression probandresults patient found harbor c2355+1gc splicing variant tsc2 gene sequencing cdna confirmed 62 bases inserted 3 end exon 21 caused frameshift producing truncated proteinconclusion novel splicing variant c2355+1gc tsc2 gene probably underlay tsc proband finding expanded variant spectrum tsc2 provided basis preimplantation genetic testing prenatal diagnosispmid34096024 doi103760 cmajcn5113742020021100072,0.0
dualtask speech performance multiple sclerosis abstractbackgroundalthough extant dualtask studies suggest cognitivemotor interference may magnify existing nonspeech motor impairments multiple sclerosis ms cognitivespeech motor interference ms studied study evaluated presence cognitivespeech motor interference ms explored within subject differences speech measures singleto dualtask condition individuals ms cooccurring dysarthria impaired cognitionmethodsin dualtask study 21 individuals ms 21 controls read aloud sentence singletask completed cognitivelinguistic task simultaneously reading aloud sentence dualtask speech measures included speech articulation rate silent pause frequency duration total sentence durationresultsboth groups significantly slower speech dualtask condition relative participants dysarthria speech rate sentence duration difference scores approached significance significantly greater participants ms dysarthria cognitive impairment difference scores associated executive function processing speed deficits fewer years educationconclusionsignificant negative compounding effects speech rate sentence duration suggest dualtask paradigm shows promise identifying individuals ms cognitive impairment dysarthria increased risk problems effective communication research warranted replicate work evaluate consequences speech aberrancies communication effectiveness ultimately may affect employment social relationships quality life,0.0
protection antigenprimed effector t cells glucocorticoidinduced apoptosis cell culture mouse model multiple sclerosis front immunol 2021 jun 10 12671258 doi 103389 fimmu2021671258 ecollection 2021abstractinduction t cell apoptosis constitutes major mechanism therapeutically administered glucocorticoids gcs suppress inflammation associated clinical symptoms instance multiple sclerosis ms patients suffering acute relapse sensitivity t cells gc action depends maturation activation status precise effect antigenpriming pathological setting explored used transgenic congenic mouse models compare gcinduced apoptosis nave antigenspecific effector t cells mice immunized myelin peptide antigenprimed effector t cells protected proapoptotic activity synthetic gc dexamethasone dosedependent manner resulted accumulation relative nave t cells vitro vivo notably differential sensitivity t cells gcinduced apoptosis correlated expression level antiapoptotic proteins bcl2 bclxl loss mitochondrial membrane potential moreover accumulation antigenprimed effector t cells following gc treatment vitro resulted aggravated disease course adoptive transfer mouse model ms vivo highlighting clinical relevance observed phenomenon collectively data indicate antigenpriming influences t cells sensitivity therapeutically applied gcs context inflammatory diseasespmid34177911 pmcpmc8222504 doi103389 fimmu2021671258,1.0
uncharted waters mesenchymal stem cell treatment pediatric refractory rheumatic diseases single center case series background advent innovative therapies including biologics janus kinase inhibitors children rheumatic diseases likely improved outcomes despite advances children respond parents fear adverse events seek alternatives increasingly private companies offering mesenchymal stem cells msc alternative described natural therapies rheumatic diseases often insinuating cure msc immunomodulatory properties transplantation stem cells used successfully treat immunologic conditions like graftversushost disease lately msc research adult lupus encouraging clinical trials still underway msc therapy standalone treatment retrospective case series will highlight three cases pediatric refractory autoimmune disease whose parents sought received msc therapy selfdecision without first seeking medical advice specialty three families felt children improved two believed child cured msc potential beneficial immunomodulation may powerful tool therapy rheumatic disease well controlled clinical trials necessary designed monitored experts childhood rheumatic diseasecase presentationthree children three different rheumatic diseases systemic lupus erythematosus mixed connective tissue disease juvenile idiopathic arthritis care pediatric rheumatology large tertiarycare teaching institution multiple nonbiologic biologic diseasemodifying antirheumatic drugs failed significantly decrease disease activity result families chose undergo msc therapy transplantation children improved per patient parent report tapered conventional immunosuppressive drugs serious adverse events occurred three patientsconclusionthe three cases presented report reflect comparable beneficial outcomes minimal risks published adult studies controlled studies however benefit reported rather documented cases suggest msc transplantation may prove promising adjunctive treatment option however research development standardized infusion therapy protocols welldesigned monitored clinical trials essential,0.0
using multiple sclerosis resiliency scale identify psychological distress persons multiple sclerosis abstractbackgroundthe multiple sclerosis resiliency scale msrs first resilience measure specific multiple sclerosis ms related challenges order msrs valuable tool clinicians important identify meaningful score study aimed examine msrsnull ability identify persons ms experiencing depression anxiety symptoms determined using clinically significant scores hospital anxiety depression scale hads methodsparticipants n884 persons ms recruited electronically primarily north american research committee ms narcoms addition msrs participants completed hads used categorize possible depression anxiety groups using two criteria literature 8 11 receiveroperatingcharacteristic roc curves run determine msrs total subscale scoresnull classification accuracies optimal scores detecting possible depression anxiety cases determined using youden indexresultsthe msrs total scorenulls classification accuracy ranged 862 922 depression scores 70 68 8 11 criteria respectively anxiety msrs total scorenulls classification accuracy ranged 781 828 scores 72 71 8 11 criteria respectively emotional cognitive strategies subscale strongest classification accuracy subscalesconclusionsthe msrs can used identify persons ms experiencing mental health difficulties relatively good classification accuracy may help clinicians triage needs additional assistance support,0.0
immunomodulation eliminates inflammation hippocampus experimental autoimmune encephalomyelitis ameliorate anxietylike behavior front immunol 2021 jun 10 12639650 doi 103389 fimmu2021639650 ecollection 2021abstractmultiple sclerosis ms autoimmune disease targeting central nervous system characterized unpredictable disease course wide range symptoms emotional cognitive deficits now recognized primary disease manifestations simply consequence living chronic condition raising questions regarding efficacy current therapeutics specific symptoms mechanisms underlying psychiatric sequelae ms believed similar underlying pathogenesis mediated cytokines inflammatory mediators gain insight pathogenesis ms depression performed behavioral assays murine experimental autoimmune encephalomyelitis eae ms model presence absence immunomodulation using drug fty720 analogue lipid signaling molecule sphingosine1phosphate s1p specifically mice challenged elevated plus maze epm test validated experimental paradigm rodentspecific anxietylike behavior fty720 treatment failed ameliorate anxietylike symptoms irrespective dosage hand effective reducing inflammatory infiltration microglial reactivity levels proinflammatory molecules hippocampus confirming antiinflammatory capacity treatment explore absence fty720 effect behavior confirmed expression s1p receptors s1pr s1pr1 s1pr3 s1pr5 hippocampus mapped dynamics receptors response drug treatment alone combination eae induction identified complex pattern responses differing 1 receptors 2 dosage 3 hippocampal subfield fty720 treatment absence eae resulted overall downregulation s1pr1 s1pr3 s1pr5 exhibited dosedependent upregulation eae induction alone resulted overall downregulation three receptors hand combined fty720 eae showed generally effect s1pr1 s1pr3 expression except fimbrium region strong upregulation s1pr5 range doses examined data illustrate hitherto undescribed complexity s1pr response fty720 hippocampus independent drug effect effector immune cells simultaneously emphasize need explore novel treatment strategies specifically address mood disorders mspmid34177891 pmcpmc8222726 doi103389 fimmu2021639650,0.0
immune response neurological pathology emerging role central peripheral immune crosstalk front immunol 2021 jun 10 12676621 doi 103389 fimmu2021676621 ecollection 2021abstractneuroinflammation key component neurological disorders important therapeutic target however immunotherapies largely unsuccessful cases therapies succeeded particularly multiple sclerosis primarily focused one aspect disease leave room improvement recently impact peripheral immune system recognized since become evident central nervous system immuneprivileged thought review highlight key interactions central peripheral immune cells neurological disorders traditional approaches examined systems separately immune responses processes neurological disorders consist substantial crosstalk cells central peripheral immune systems provide overview major immune effector cells role bloodbrain barrier regard neurological disorders provide examples crosstalk various disorders including stroke traumatic brain injury multiple sclerosis neurodegenerative diseases brain cancer finally propose targeting centralperipheral immune interactions potential improved therapeutic strategy overcome failures clinical translationpmid34177918 pmcpmc8222736 doi103389 fimmu2021676621,0.0
migraine neuroinflammation inflammasome perspective background neuroinflammation important role pathophysiology migraine complex neurogliovascular disorder main aim review highlight findings cortical spreading depolarization csd induced neuroinflammatory signaling brain parenchyma inflammasome perspective addition discuss limited data contribution inflammasomes aspects migraine pathophysiology foremost activation trigeminovascular system thereby generation migraine painmain bodyinflammasomes signaling multiprotein complexes key components innate immune system activation causes production inflammatory cytokines can stimulate trigeminal neurons thus relevant generation migraine pain contribution inflammasome activation pain signaling attracted considerable attention recent years nucleotidebinding domain nod like receptor family pyrin domain containing 3 nlrp3 best characterized inflammasome emerging evidence role variety inflammatory pain conditions including migraine review discuss inflammasome point view cortical spreading depolarization csd induced neuroinflammatory signaling brain parenchyma connection genetic factors make brain vulnerable csd relation inflammasome diseases comorbid migraine including stroke epilepsy possible links covid19 infectionconclusionneuroinflammatory pathways specifically involving inflammasome proteins seem promising candidates treatment targets perhaps even biomarkers migraine,0.0
mir155 functional proteins cd8+ t cells potential prognostic biomarkers relapsingremitting multiple sclerosis abstractbackgroundmultiple sclerosis ms chronic inflammatory disease central nervous system cns results neurological deficits patients leading disabilities evaluated scale known expanded disability status scale edss prevalent subtype disease relapsingremitting multiple sclerosis rrms one key players ms pathogenesis cd8+ t cells present abundance ms lesions expressing surface receptors intracellular adhesion molecule icam1 integrin subunit beta 2 itgb2 proteins crucial migration bloodbrain barrier bbb secondary stimulatory signal along cytotoxic proteins perforin granzymeb attack oligodendrocytes micrornas mirnas small noncoding rnas play substantial regulatory role various disease pathogeneses posttranscriptional modifications mir155 shows potential use biomarker disease study aims investigating expression mir155 icam1 itgb2 perforin granzymeb cd8+ t cells rrms patients receiving different treatment regimens genes correlate patientsnull edss mir155 expressionmethodsgene expression mir155 icam1 itgb2 perforin granzymeb evaluated using rtqpcr cd8+ t cells isolated blood samples rrms patients compared healthy controlsresultsresults showed downregulation mir155 upregulation surface receptors cytotoxic proteins cd8+t cells significant correlation patientsnull edssconclusionthis study helps pave road discussed genes use potential biomarkers disease disability future investigations regulatory roles disease pathogenesis,0.0
altered expression micrornas b lymphocytes natalizumab therapy multiple sclerosis heliyon 2021 jun 9 7 6 e07263 doi 101016 jheliyon2021e07263 ecollection 2021 junabstractmicrornas mirnas family nontranslated small ribonucleic acids rnas measuring 2125 nucleotides length play various roles multiple sclerosis ms regulating gene expression via either mediating translational repression cleavage target rna mirnas can alter expression transcripts different cells b lymphocytes also known b cells crucial pathogenesis ms however extensively studied treatment drugs natalizumab ntz ntz humanized immunoglobulin g4 antibody antagonist integrin alpha 4 4 used treatment ms drug reduces homing lymphocytes inflammation sites integrin 4 expression cell surface b cells related ms severity indicating critical component pathogenesis disease ntz plays important role modifying gene expression b cells levels mirnas treatment ms review described changes gene expression b cells levels mirnas ntz therapy ms relapse studies using experimental autoimmune encephalomyelitis eae model involving patients ms described changes levels micrornas regulation proteins affected specific mirnas gene expression b cells certain functions b cells well subpopulations therefore possibility mirnas studied different stages ms ntz treatment specific mirnas can tested markers therapeutic response drug future studies physiopathology gene expression b cells subpopulations can help understand complex puzzle involving mirnas therapeutic response patients mspmid34179535 pmcpmc8214090 doi101016 jheliyon2021e07263,0.0
nacetylcysteine review clinical usefulness old drug new tricks j nutr metab 2021 jun 9 20219949453 doi 101155 2021 9949453 ecollection 2021abstractobjective review clinical usefulness nacetylcysteine nac treatment adjunctive therapy number medical conditions use tylenol overdose cystic fibrosis chronic obstructive lung disease well documented emerging evidence many conditions benefit safe simple inexpensive intervention quality evidence pubmed several books conference proceedings searched articles nac health conditions listed reviewing supportive evidence study uses traditional integrated review format clinically relevant information assessed using american family physician evidencebased medicine toolkit table summarizing potential mechanisms action nacetylcysteine conditions presented main message nacetylcysteine may useful adjuvant treating various medical conditions especially chronic diseases conditions include polycystic ovary disease male infertility sleep apnea acquired immune deficiency syndrome influenza parkinsonism multiple sclerosis peripheral neuropathy stroke outcomes diabetic neuropathy crohns disease ulcerative colitis schizophrenia bipolar illness obsessive compulsive disorder can also useful chelator heavy metals nanoparticles also number conditions may show benefit however evidence robustconclusion use nacetylcysteine considered number conditions population ages levels glutathione drop supplementation may contribute reducing morbidity mortality chronic conditions outlined articlepmid34221501 pmcpmc8211525 doi101155 2021 9949453,0.0
dualities vitamin d systemic sclerosis systematic literature review background systemic sclerosis ssc chronic disease characterized autoimmunity vasculopathy visceral cutaneous fibrosis vitamin d several functions immunological system different studies suggested potential role triggering autoimmune diseases patients ssc may present low serum levels vitamin d association hypovitaminosis d disease onset clinical manifestation still obscure goal verify causal relationship hypovitaminosis d ssc onset particular clinical manifestation literaturemethodsa systematic literature review performed february 24th 2021 pubmed lilacs bireme cochrane databases eligible studies read full text absence exclusion criteria included review consensus two reviewersresultsforty articles met eligibility criteria main results study described studies ssc patients showed higher prevalence vitamin d deficiency insufficiency compared controls additionally reports serum levels vitamin d inversely correlated severity ssc oral supplementation seem affect serum levels vitamin d four included studies experimental modelsconclusionin conclusion vitamin d deficiency seems role susceptibility ssc well clinical manifestations disease,0.0
serum antidido1 anticpsf2 antifoxj2 antibodies predictive risk markers acute ischemic stroke background acute ischemic stroke ais serious cause mortality disability ais serious cause mortality disability early diagnosis atherosclerosis major cause ais allows therapeutic intervention onset leading prevention aismethodsserological identification cdna expression cdna libraries protein array method used screening antigens recognized serum igg antibodies patients atherosclerosis recombinant proteins synthetic peptides derived candidate antigens used antigens compare serum igg levels healthy donors hds patients atherosclerosisrelated disease using amplified luminescent proximity homogeneous assaylinked immunosorbent assayresultsthe first screening using protein array method identified deathinducer obliterator 1 dido1 forkhead box j2 foxj2 cleavage polyadenylation specificity factor cpsf2 target antigens serum igg antibodies patients ais prepared various antigens including glutathione stransferasefused dido1 protein well peptides amino acids 297311 dido1 426440 foxj2 607621 cpsf2 examine serum antibody levels compared hds significant increase antibody levels dido1 protein peptide patients ais transient ischemic attack tia chronic kidney disease ckd acute myocardial infarction diabetes mellitus dm serum antifoxj2 antibody levels elevated patients atherosclerosisrelated diseases whereas serum anticpsf2 antibody levels associated ais tia dm receiver operating characteristic curves showed serum dido1 antibody levels highly associated ckd correlation analysis revealed serum antifoxj2 antibody levels associated hypertension prospective casecontrol study ischemic stroke verified serum antibody levels dido1 protein dido1 foxj2 cpsf2 peptides showed significantly higher odds ratios risk ais patients highest quartile lowest quartile indicating antibody markers useful risk factors aisconclusionsserum antibody levels dido1 foxj2 cpsf2 useful predicting onset atherosclerosisrelated ais caused kidney failure hypertension dm respectively,0.0
serial magnetic resonance imaging changes pseudotumor lesions retinal vasculopathy cerebral leukoencephalopathy systemic manifestations case report background retinal vasculopathy cerebral leukoencephalopathy systemic manifestations rvcls adultonset rare monogenic microvasculopathy typical neuroimaging features punctate white matter lesions pseudotumor alterations rvcls often underrecognized misdiagnosed rarity similar imaging manifestations multiple sclerosis brain malignant masscase presentationhere report case 36yearold chinese man developed multiple tumefactive brain lesions spanning two years leading motor aphasia cognitive decline limb weakness also presented slight vision loss fundus fluorescein angiography indicated retinal vasculopathy underwent brain biopsies twice showed evidence malignancy given family history father died brain mass unclear etiology rvcls suspected genetic analysis confirmed diagnosis heterozygous insertion mutation threeprime repair exonuclease 1 gene given courses corticosteroids cyclophosphamide received little responseconclusionsthe present case one published reports rvcls twoyear detailed imaging data serial magnetic resonance images showed progression pattern lesions experience emphasizes better understanding rvcls considering differential diagnosis patients tumefactive brain lesions may help avoid unnecessary invasive examinations make earlier diagnosis,0.0
timed 25foot walk large cohort multiple sclerosis patients abstractbackgroundthe timed 25foot walk t25fw key clinical outcome measure multiple sclerosis patient management clinical researchobjectivesto evaluate t25fw performance factors associated change multiple sclerosis outcome assessments consortium msoac placebo database n2465 methodswe created confirmed disability progression cdp variables t25fw expanded disability status scale edss outcomes used intraclass correlation coefficients iccs bland altman plots evaluate reliability evaluated t25fw changes predictive validity using mixedeffects model survival analysis nested casecontrol analysisresultsthe mean baseline score t25fw study population 92seconds median61 standard deviation110 interquartile range iqr 48 90 t25fw measure demonstrated excellent testretest reliability icc098 walk times increased age disability disease type disease duration relapses associated increase patients t25fw progression faster time edsscdp compared without hazards ratio hr 26 confidence interval ci 22 31 changes t25fw likely precede changes edssconclusionthis research confirms association t25fw disability provides evidence predictive validity findings support continued use t25fw clinical practice clinical trials,0.0
genes environment multiple sclerosis impact temporal changes sex ratio recurrence risks abstractobjectiveto evaluate impact temporal increase female male fm sex ratio persons multiple sclerosis ms familial risk empiric recurrence risks rrs biological relatives affected individualsmethodsdetailed family histories systematically obtained people ms attending university british columbia hospital ms clinic study cohort born 1970 recently data collected 1 september 2015 31 january 2019 study designed allow one proband per family agecorrected rrs biological relatives probands calculated based modification maximumlikelihood approachresultsdata analyses possible 746 unique probands 531 females 215 males 19 585 biological relatives rrs temporally impactedconclusionboth genetic sharing environmental factors important determining rrs appears increase ms risk due environmental factors later life ie shared family environment environmental exposures genetically predisposed individuals might driving ms risk increase fm ratio rrs sisters brothers female probands time likely due environmental differences,0.0
early glycolytic reprogramming controls microglial inflammatory activation background microglial activationmediated neuroinflammation plays important role progression neurodegenerative diseases inflammatory activation microglial cells often accompanied metabolic switch oxidative phosphorylation aerobic glycolysis however roles molecular mechanisms glycolysis microglial activation neuroinflammation yet fully understoodmethodsthe antiinflammatory effects underlying mechanisms glycolytic inhibition vitro examined lipopolysaccharide lps activated bv2 microglial cells primary microglial cells enzymelinked immunosorbent assay elisa quantitative reverse transcriptasepolymerase chain reaction rtpcr western blot immunoprecipitation flow cytometry nuclear factor kappa b nfb luciferase reporter assays antiinflammatory neuroprotective effects glycolytic inhibitor 2deoxoydglucose 2dg vivo measured 1methyl4phenyl1 2 3 6tetrahydropyridine mptp lpsinduced parkinsons disease pd models immunofluorescence staining behavior tests western blot analysisresultswe found lps rapidly increased glycolysis microglial cells glycolysis inhibitors 2dg 3bromopyruvic acid 3bpa sirna glucose transporter type 1 glut1 sirna hexokinase hk 2 abolished lpsinduced microglial cell activation mechanistic studies demonstrated glycolysis inhibitors significantly inhibited lpsinduced phosphorylation mechanistic target rapamycin mtor inhibitor nuclear factorkappa b kinase subunit beta ikk nfkappab inhibitor alpha ib degradation ib nuclear translocation p65 subunit nfb nfb transcriptional activity addition 2dg significantly inhibited lpsinduced acetylation p65 rela lysine 310 mediated naddependent protein deacetylase sirtuin1 sirt1 critical nfb activation coculture study revealed 2dg reduced cytotoxicity activated microglia toward mes235 dopaminergic neuron cells direct protective effect lpsinduced pd model 2dg significantly ameliorated neuroinflammation subsequent tyrosine hydroxylase th positive cell loss furthermore 2dg also reduced dopaminergic cell death microglial activation mptpinduced pd modelconclusionscollectively results suggest glycolysis actively involved microglial activation inhibition glycolysis can ameliorate microglial activationrelated neuroinflammatory diseases,1.0
derepression transposable elements lung cells associated inflammatory response gene activation idiopathic pulmonary fibrosis background transposable elements tes repetitive sequences viral origin compose almost half human genome elements tightly controlled within cells activated can cause changes gene regulation immune viral responses associated several chronic inflammatory diseases humans oxidants potent activators tes oxidative injury major risk factor relation idiopathic pulmonary fibrosis ipf hypothesized tes might involved regulation gene expression contribute inflammation cases ipf ipf fatal lung disease involves gradual replacement alveolar tissue fibrotic scars well accumulation inflammatory cells lower respiratory tract although ipf known occur result complex interaction age environmental risk factors ie oxidative stress genetics relative contributions factors disease remain unclear determine whether tes associated ipf compared transcriptional profiles genes tes lung cells obtained healthy donors ipf patientsresultswe quantified te gene expression levels using published bulk rnaseq dataset containing 24 subjects 16 donors eight ipf patients including three lungcell types per subject well scrnaseq dataset concerning 16 subjects eight donors eight ipf patients found evidence te dysregulation alveolar type ii lung cells alveolar macrophages ipf patients addition activation line1 family elements ipf associated increased expression te cellular regulators mov10 ifi16 samhd1 apobecg3 interferonstimulating genes isg15 ifi6 ifi27 ifi44 oas1 chemokines cx3cl1 cxcl9 interleukins il15ra also propose te derepression might involved regulation previously reported ipf candidate genes muc5b chl1 spp1 mmp7 conclusionbased findings propose te derepression plays important role regulation gene expression can also prompt recruitment inflammatory processes disruption immunological balance can lead chronic inflammation ipf,0.0
association lipoproteins thyroid hormones cognitive dysfunction patients systemic lupus erythematosus background neuropsychiatric manifestations occur 75 adult systemic lupus erythematosus sle patients one major causes death sle patients cognitive dysfunction typical clinical feature neuropsychiatric sle npsle seriously affects quality life patients dyslipidaemia thyroid symptoms prevalent sle patients related neuropsychiatric disturbances including significant psychiatric cognitive disturbances study aimed investigate whether cognitive dysfunction patients sle related expression serum thyroid hormone lipoprotein levelsmethodsa total 121 patients sle 65 healthy controls hcs nanjing drum tower hospital completed cognitive function test 81 sle patients divided highcognition n 33 group lowcognition group n 48 clinical laboratory characteristics patients compared moreover correlations serum hdlc ldlc ft3 ft4 levels cognitive function analysed serum levels apoe apoa1 igf1 igfbp7 81 patients detected elisa correlation four proteins cognition analysed separatelyresultsthe patients sle abnormal cognitive function less educated hcs lowcognition patients levels albumin ft3 p 005 ft4 decreased ddimer antidsdna antibody igm levels increased serum ft3 ft4 levels positively correlated cognition furthermore serum protein levels apoe apoa1 showed difference high lowcognition groups however serum apoe levels negatively correlated line orientation scores apoa1 levels positively correlated coding scoresconclusionsserum ft3 ft4 levels positively correlated four indexes cognition language exception serum apoe levels negatively correlated line orientation scores apoa1 levels positively correlated coding scores igfbp7 levels negatively correlated figure copy scores results demonstrated ft3 ft4 might clinical biomarkers cognitive dysfunction sle,0.0
network medicine links sarscov2 covid19 infection brain microvascular injury neuroinflammation dementialike cognitive impairment background dementialike cognitive impairment increasingly reported complication sarscov2 infection however underlying mechanisms responsible complication remain unclear better understanding causative processes covid19 may lead cognitive impairment essential developing preventive therapeutic interventionsmethodsin study conducted networkbased multimodal omics comparison covid19 neurologic complications constructed sarscov2 virushost interactome proteinprotein interaction assay crisprcas9based genetic assay results compared networkbased relationships therein known neurological manifestations using network proximity measures also investigated transcriptomic profiles including singlecell nuclei rnasequencing alzheimers disease ad marker genes patients infected covid19 well prevalence sarscov2 entry factors brains ad patients infected sarscov2resultswe found significant networkbased relationships covid19 neuroinflammation brain microvascular injury pathways processes implicated ad also detected aberrant expression ad biomarkers cerebrospinal fluid blood patients covid19 transcriptomic analyses showed relatively low expression sarscov2 entry factors human brain neuroinflammatory changes pronounced addition singlenucleus transcriptomic analyses showed expression sarscov2 host factors bsg furin antiviral defense genes ly6e ifitm2 ifitm3 ifnar1 elevated brain endothelial cells ad patients healthy controls relative neurons cell types suggesting possible role brain microvascular injury covid19mediated cognitive impairment overall individuals ad risk allele apoe e4 e4 displayed reduced expression antiviral defense genes compared apoe e3 e3 individualsconclusionour results suggest significant mechanistic overlap ad covid19 centered neuroinflammation microvascular injury results help improve understanding covid19associated neurological manifestations provide guidance future development preventive treatment interventions although causal relationship mechanistic pathways covid19 ad need future investigations,0.0
validity reliability georgianlanguage brief international cognitive assessment multiple sclerosis bicams background cognitive impairment one common features multiple sclerosis ms despite high prevalence cognitive decline often overlooked neurologists brief international cognitive assessment ms bicams therefore introduced international expert committee brief effective tool assessment monitoring cognitive functions patients ms validity reliability bicams demonstrated many countries aim validate bicams georgian patients msmethodsa total 68 patients ms 68 matched controls assessed georgianlanguage bicams healthy controls seven patients reevaluated identical tests assess retest reliabilityresultsin comparison healthy controls patients ms performed significantly worse tests assessment battery testretest reliability measures good tests prevalence cognitive impairment patients ms 43conclusionthe georgianlanguage bicams reliable valid battery assessment cognitive function patients ms,0.0
membranous nephropathy associated multicentric castlemans disease successfully treated tocilizumab case report review literature background multicentric castlemans disease lifethreatening disorder involving systemic inflammatory response multiple organ failure caused overproduction interleukin6 although renal complications castlemans disease include aa amyloidosis thrombotic microangiopathy membranoproliferative glomerulonephritis membranous nephropathy relatively rare experienced case secondary membranous nephropathy associated castlemans diseasecase presentationthe patient 43yearold japanese man shown high zinc sulfate value turbidity test polyclonal hypergammaglobulinemia anemia proteinuria physical examination revealed diffuse lymphadenopathy enlarged spleen papulae body trunk skin biopsy papule patients back showed plasma cells perivascular area diagnosed multicentric castlemans disease plasma cell variant kidney biopsy showed appearance bubbling glomerular basement membranes periodic acid methenamine silver stain electron microscopy revealed electron dense deposits within outside glomerular basement membranes since immunofluorescence study showed predominant granular deposition igg1 igg2 diagnosed secondary membranous nephropathy associated castlemans disease initially treated prednisolone alone however biochemical abnormalities improve intravenous tocilizumab 700 mg every 2 weeks started creactive protein elevation anemia polyclonal gammopathy improved furthermore urinary protein level declined 158 g gcr 013 g gcr prednisolone dose gradually tapered discontinued stable without recurrence proteinuria 6 monthsconclusionstocilizumab might treatment option secondary membranous nephropathy associated castlemans disease,0.0
motor cortical activation assessment progressive multiple sclerosis patients enrolled gait rehabilitation secondary analysis ragtime trial assisted functional nearinfrared spectroscopy diagnostics basel 2021 jun 9 11 6 1068 doi 103390 diagnostics11061068abstractthis study aimed determine cortical activation responses two different rehabilitative programs measured functional nearinfrared spectroscopy fnirs secondary analysis ragtime trial studied 24 patients progressive multiple sclerosis ms severe disability randomized regimen robotassisted gait training ragt overground walking ow cortical activation treadmill walking task assessed fnirs recordings motor premotor cortexes m1 pm calculated area curve auc oxyhemoglobin hemisphere total area totoxyauc gait speed endurance balance also measured along five healthy control subjects baseline totoxyauc walking significantly increased ms patients compared healthy people significantly higher severe disabilities also inversely correlated physical performance rehabilitation significant opposite variations totoxyauc observed activity levels increased ow decreased ragt +242 080 361 902 157 031 172 496 arbitrary units respectively p 0002 particularly patients trained lower speed greater reductions cortical activation affected hemisphere significantly related improvements gait speed r 042 endurance r 044 cortical activation assessed fnirs highlighted brain activity response type intensity rehabilitationpmid34207923 doi103390 diagnostics11061068,1.0
hgf met brain development neurological disorders front cell dev biol 2021 jun 9 9683609 doi 103389 fcell2021683609 ecollection 2021abstracthepatocyte growth factor hgf tyrosine kinase receptor encoded met cellular protooncogene expressed nervous system prenatal development adult life involved neuronal growth survival review highlight beyond neurotrophic action novel roles hgfmet synaptogenesis postnatal brain development connection deregulation met expression developmental disorders autism spectrum disorder asd pharmacology side hgfinduced met activation exerts beneficial neuroprotective effects also adulthood specifically neurodegenerative disease preclinical models cerebral ischemia spinal cord injuries neurological pathologies alzheimers disease ad amyotrophic lateral sclerosis als multiple sclerosis ms hgf key factor preventing neuronal death promoting survival proangiogenic antiinflammatory immunemodulatory mechanisms recent evidence suggests hgf acts neural stem cells enhance neuroregeneration possible therapeutic application hgf hgf mimetics treatment neurological disorders discussedpmid34179015 pmcpmc8220160 doi103389 fcell2021683609,1.0
sitespecific resolution enthesitis patients axial spondyloarthritis treated tumor necrosis factor inhibitors background enthesitis hallmark spondyloarthritis spa substantial impact quality life reports treatment effectiveness across individual enthesitis sites realworld patients axial spa axspa limited investigated evolution enthesitis following tumor necrosis factor inhibitor tnfi initiation axspa patients cumulatively specific axial peripheral sitesmethodsaxspa patients swiss clinical quality management registry included initiated tnfi available maastricht ankylosing spondylitis enthesitis score modified include plantar fascia mmases 015 start treatment 6 12 months 12 months followup logistic regression models utilized analyze explanatory variables enthesitis resolutionresultsoverall 1668 tnfi treatment courses tcs included 1117 67 active enthesitis baseline reduction mmases 6 12month timepoints experienced 72 70 tcs respectively enthesitis resolution 6 12 months occurred 379 430 tnfi tcs 407 509 first tnfi tcs 6 months significant reduction frequency enthesitis observed sites except achilles tendon plantar fascia among first tnfi tcs 12 months reduction significant sites tc groups enthesitis resolved 60377 across anatomical sites new incident enthesitis occurred 40135 tnfi tcs 12 months baseline newincident enthesitis occurred frequently posterior superior iliac spine fifth lumbar spinous process younger age lower mmases baseline predictors complete enthesitis resolution female sex second laterline tnfi treatment associated persistence enthesitis 12 monthsconclusionin realworld axspa patients treated tnfi enthesitis improved majority patients across anatomical sites significant improvement achilles plantar fascia entheses observed 12 months complete sitespecific enthesitis resolution occurred 40 60 tcs evaluated 12 months low incidence new sitespecific enthesitistrial registrationnot applicable,0.0
rheumatologist perspective brazilian consensus detection auto antibodies hep2 cells abstractobjectiveto evaluate perception rheumatologists regarding recommendations brazilian consensus detection autoantibodies bca hep2 cells indirect immunofluorescence assay ifa bca recommendations help clinical practicemethodologya structured questionnaire regarding bca recommendations detection interpretations autoantibodies hep2 cells applied randomly selected rheumatologists results tabulated using microsoft excel program expressed simple percentage dichotomous data analyzed using chisquare test epi info programresultsfour hundred fuorteen rheumatologists participated study 70 considered knowledge hep2 ifa test satisfactory excellent 43 said knew bca recommendations general without distinguishing edition bca refer revista brasileira de rheumatologia advances rheumatology means dissemination consulted specialists 50 according rheumatologists opinion relevant pattern homogeneous nuclear 78 65 stated satisfied bca recommendations level satisfaction greater equal 80 significant difference perception rheumatologists several brazilian geographic regionsconclusionbrazilian rheumatologists aware bca guidelines satisfied content published considering bca recommendations assist positively clinical practice rheumatologists recognize patterns associated rheumatic autoimmune diseases used bca recommendations interpret results hep2 ifa test,0.0
realworld experience ocrelizumab multiple sclerosis patients latin america abstract background despite abundance information concerning ocrelizumab phase iii clinical trials scarce evidence regarding realworld patient profiles objective aim study investigate patient profiles effectiveness persistence treatment among patients used ocrelizumab treatment multiple sclerosis latin america methods retrospective multicenter study argentina chile mexico medical record databases patients received ocrelizumab analyzed demographic clinical variables described along effectiveness outcomes included proportions patients free clinical relapses disability progression new enlarging t2 t1 gadoliniumenhancing lesions annual magnetic resonance imaging results total 81 patients included frequent phenotype relapsingremitting ms 642 patients mean age study entry 413 120 years 518 women total 38 relapse activity 12 months starting ocrelizumab mean relapse rate 13 06 period 75 free clinical relapses 91 free gadoliniumenhancing lesions relapsingremitting course ocrelizumab discontinuation first 12 months observed three patients 37 mean persistence observed firstyear followup 338 24 days conclusions study line previous randomized clinical trials recent realworld studies describing patient profiles effectiveness persistence regarding ocrelizumab treatment multiple sclerosis patients latin america,0.0
altered blood levels antigal antibodies alzheimer#39 s disease new clue pathogenesis life basel 2021 jun 9 11 6 538 doi 103390 life11060538abstractalzheimers disease neurodegenerative disorder whose pathological mechanisms despite recent advances fully understood however deposition beta amyloid peptide neuroinflammation probably aggravated dysbiotic microbiota seem play key role antigal abundant xenoreactive natural antibodies supposed stem immunization gut microbiota implicated pathogenesis several diseases including multiple sclerosis antibodies target alphagal epitope expressed terminal sugar units glycoprotein glycolipid mammals except apes old world monkeys humans alphagal constitutively expressed several bacteria constituting brain microbiota alphagallike epitopes detected gray matter amyloid plaque neurofibrillary tangles corpora amylacea human brain suggesting potential link antigal alzheimers disease etiopathogenesis first time study searched possible alterations antigal immunoglobulin levels alzheimers disease patients igg igm blood levels significantly lower iga significantly higher patients healthy subjects results suggest immunoglobulins might implicated alzheimers disease pathogenesis open new scenarios research new biomarkers therapeutic strategiespmid34207559 doi103390 life11060538,0.0
tacrolimus protects ageassociated microstructural changes beagle brain overexpression calcineurin leads astrocyte hyperactivation neuronal death inflammation characteristics often associated pathologic aging alzheimer9s disease study tested hypothesis tacrolimus calcineurin inhibitor prevents ageassociated microstructural atrophy measured using higherorder diffusion mri middleaged beagle brain n 30 male female find tacrolimus reduces hippocampal p 0001 parahippocampal p 0002 neurite density index well protects ageassociated increase parahippocampal p 0007 orientation dispersion index tacrolimus also protects agerelated decrease fractional anisotropy prefrontal cortex p 00001 also show microstructural alterations precede cognitive decline gross atrophy results support idea calcineurin inhibitors may potential prevent agingrelated pathology administered middle agesignificance statement hyperactive calcineurin signaling causes neuroinflammation neurobiological changes often associated pathologic aging alzheimer9s disease ad controlling expression calcineurin gross cognitive deficits observable might serve promising avenue preventing ad pathology study show administration calcineurin inhibitor tacrolimus 1 year prevents age adassociated microstructural changes hippocampus parahippocampal cortex prefrontal cortex middleaged beagle brain noticeable adverse effects tacrolimus already approved food drug administration use humans prevent solid organ transplant rejection results bolster promise drug prevent ad agingrelated pathology,0.0
pregnancyinduced effects memory bcell development multiple sclerosis sci rep 2021 jun 9 11 1 12126 doi 101038 s41598021916559abstractin ms pathogenic memory b cells infiltrate brain develop antibodysecreting cells chemokine receptors define braininfiltrating capacity also assist maturation germinal centers corresponds pregnancy naturally occurring modifier ms underexplored aimed study impact pregnancy ex vivo vitro bcell differentiation ms composition outgrowth peripheral b cells compared 19 ms pregnant patients 12 healthy controls third trimester pregnancy low relapse risk postpartum high relapse risk transitional naive mature bcell frequencies found drop third trimester prominent patients experienced prepregnancy relapse early delivery frequencies raised memory b cell frequencies modestly declined cxcr4 downregulated cxcr5 cxcr3 ccr6 upregulated postpartum memory b cells implying enhanced recruitment germinal center light zones interaction t follicular helper tfh cells postpartum memory b cells ms patients expressed higher levels ccr6 preferentially developed plasma cells tfhlike vitro conditions findings imply memory b cell differentiation contributes postpartum relapse risk mspmid34108575 doi101038 s41598021916559,0.0
mild gray matter atrophy patients longstanding multiple sclerosis favorable clinical course abstractthe mechanisms responsible favorable clinical course multiple sclerosis ms remain unclear longitudinal study assessed whether magnetic resonance imaging mri based changes focal diffuse brain damage associated longterm favorable ms diseases course found global brain gray matter gm atrophy changes milder ms patients longstanding disease 30years onset favorable minimal disability clinical course sexagematched disable ms patients independently lesions accumulation data showed different trajectories volume changes reflected mild gm atrophy may characterize patients longterm favorable evolution,0.0
family functioning multiple sclerosis study protocol multicentric italian project front psychol 2021 jun 9 12668010 doi 103389 fpsyg2021668010 ecollection 2021abstractmultiple sclerosis ms chronic inflammatory neurodegenerative disease affects physical functioning also associated cognitive impairments great psychological distress combination symptoms may negative consequences family functioning patients ms detrimental effects marital relationships parental bonding furthermore presence individual characteristics adequate social support may also contribute quality endurance family relationships particularly high levels alexithymia personality trait affects recognition persons emotions associated reduced interpersonal communication skills enhanced anxiety depressive symptoms therefore main aim present study provide indepth evaluation family functioning related factors patients ms families order reach goal perceived quality family functioning dyadic relationships parental bonding will first investigated secondly possible associations quality family relationships presence alexithymia psychological distress perceived social support will examined patients ms families will consent take part study will asked provide sociodemographic clinical information complete series questionnaires presented uploaded online dedicated platform final sample will made 300 families consecutively recruited italian medical centers involved project results present study will shed light family functioning patients ms comprehensive assessment main factors associated family dynamics holistic evaluation aspects can help clinicians researchers understand family dynamics ms population betterpmid34177727 pmcpmc8219871 doi103389 fpsyg2021668010,0.0
epigenetic plasticity enables cnstrafficking ebvinfected b lymphocytes plos pathog 2021 jun 9 17 6 e1009618 doi 101371 journalppat1009618 online ahead printabstractsubpopulations blymphocytes traffic different sites organs provide diverse tissuespecific functions provide evidence epigenetic differences confer neuroinvasive phenotype ebv+ b cell lymphoma cell line m14 low frequency trafficking cns neuroadapted generate highly neuroinvasive bcell population mun14 mun14 b cells efficiently infiltrated cns within one week produced neurological pathologies compared gene expression profiles viral cellular genes using rnaseq identified one viral ebna1 several cellular gene candidates including secreted phosphoprotein 1 osteopontin spp1 opn neuron navigator 3 nav3 cxcr4 germinal centerassociated signaling motility protein gcsam selectively upregulated mun14 atacseq chipqpcr revealed gene expression changes correlated epigenetic changes gene regulatory elements neuroinvasive phenotype attenuated neutralizing antibody opn confirming functional role protein trafficking ebv+ b cells cns studies indicate bcell trafficking cns can acquired epigenetic adaptations provide new model study bcell neuroinvasion associated cns lymphoma autoimmune disease cns including multiple sclerosis ms pmid34106998 doi101371 journalppat1009618,0.0
right inferior parietal lobule activity associated handwriting spontaneous tempo front neurosci 2021 jun 9 15656856 doi 103389 fnins2021656856 ecollection 2021abstracthandwriting complex activity including motor planning visuomotor integration referring brain areas identified writing centers although temporal features handwriting important spatial ones knowledge evidence description specific brain areas associated handwriting tempo people multiple sclerosis pwms show handwriting impairments mainly referred temporal features task aim work assess differences brain activation pattern elicited handwriting pwms healthy controls hc final goal identifying possible areas specific handwriting tempo subjects asked write sentence spontaneous speed pwms differed temporal handwriting features hc showed reduced activation subset clusters observed hc spearmans correlation analysis performed handwriting temporal parameters activity brain areas resulting contrast analysis hc pwms found right inferior parietal lobule ipl negatively correlated duration sentence indicating higher right ipl activity faster handwriting performance propose right ipl might considered writing tempo centerpmid34177447 pmcpmc8219918 doi103389 fnins2021656856,0.0
gaps evidence use medically authorized cannabis ontario alberta canada background legal access medical cannabis canada since 2001 need fully characterize use individual population levels draw data canadas largest cohort study medical cannabis identify primary reasons medical cannabis authorization canada 2014 2019 two major provinces alberta ab ontario review extent evidence supports indicationmethodsselfreported baseline assessments collected adult patients n 61 835 ab n 3410 authorized medical cannabis baseline sociodemographic primary medical information validated clinical questionnaires completed patients part individual assessment patients reasons seeking medical cannabis compared published reviews guidelines assess level evidence supporting medical cannabis use conditionresultsmedical cannabis use ab similar demographic reason authorization common reasons medical cannabis authorization 1 pain ab 77 76 primarily due chronic musculoskeletal arthritic neuropathic pain 2 mental health concerns ab 329 387 due anxiety depression 3 sleep problems ab 28 25 50 conditions identified reasons obtaining authorizationconclusionin ab majority reasons medical cannabis authorization substantiated clinical evidence fully support efficacy longterm use ongoing epidemiological studies medical cannabis treatments warranted fully outline treatment benefits risks,0.0
evaluation connectivitybased imaging metric reflects functional decline multiple sclerosis plos one 2021 jun 8 16 6 e0251338 doi 101371 journalpone0251338 ecollection 2021abstractcognitive impairment common symptom individuals multiple sclerosis ms meaningful reliable biomarkers relating cognitive decline elusive making evaluation impact therapeutics cognitive function difficult combine pathwaybased mri measures structural functional connectivity construct metric functional decline ms structural functional connectivity index sfci proposed simple zscored metric structural functional connectivity changes metric simple statistical interpretation may suitable use clinical trials using data collected six time points 2year longitudinal study 20 participants ms 9 age sexmatched healthy controls probe two common symptomatic domains motor cognitive function measuring structural functional connectivity transcallosal motor pathway posterior cingulum bundle sfci significantly lower participants ms compared controls p 0009 shows significant decrease time ms p 0012 change sfci two years performed favorably compared measures brain parenchymal fraction lesion volume relating followup measures processing speed r 060 p 0005 verbal fluency r 057 p 0009 score multiple sclerosis functional composite r 067 p 0003 initial results show sfci suitable metric longitudinal evaluation functional decline mspmid34101741 doi101371 journalpone0251338,0.0
distinctive waves innate immune response retina experimental autoimmune encephalomyelitis jci insight 2021 jun 8 6 11 149228 doi 101172 jciinsight149228abstractneurodegeneration mediates neurological disability inflammatory demyelinating diseases cns role innate immune cells mediating damage remained controversial evidence destructive protective effects complicated efforts develop treatment time sequence dynamic evolution opposing functions especially unclear given limits vivo monitoring human diseases multiple sclerosis ms animal models warranted investigate association timing innate immune activation neurodegeneration using noninvasive vivo retinal imaging experimental autoimmune encephalitis eae cx3cr1gfp +knockin mice followed transcriptional profiling able show 2 distinct waves separated marked reduction number innate immune cells change cell morphology first wave characterized inflammatory phagocytic phenotype preceding onset eae whereas second wave characterized regulatory antiinflammatory phenotype chronic stage additionally magnitude first wave associated neuronal loss two transcripts identified growth arrestspecific protein 6 gas6 suppressor cytokine signaling 3 socs3 might promising targets enhancing protective effects microglia chronic phase initial injurypmid34100385 doi101172 jciinsight149228,1.0
perinatal depression anxiety multiple sclerosis treatable distress neurology 2021 apr 28101212 wnl0000000000012101 doi 101212 wnl0000000000012101 online ahead printno abstractpmid33910936 doi101212 wnl0000000000012101,0.0
prmt5 promotes cyclin e1 cell cycle progression cd4 th1 cells correlates eae severity front immunol 2021 jun 8 12695947 doi 103389 fimmu2021695947 ecollection 2021abstractmultiple sclerosis ms debilitating central nervous system disorder associated inflammatory t cells activation expansion inflammatory t cells thought behind ms relapses influence disease severity protein arginine nmethyltransferase 5 prmt5 t cell activationinduced enzyme symmetrically dimethylates proteins promotes t cell proliferation however mechanism behind prmt5mediated control t cell proliferation whether prmt5 contributes diseases severity unclear evaluated role prmt5 cyclin cdk pairs cell cycle progression well prmt5s link disease severity animal model relapsingremitting ms treatment t helper 1 mth1 cells selective prmt5 inhibitor hlcl65 arrested activationinduced t cell proliferation g1 stage cell cycle suggesting prmt5 promotes cell cycle progression cd4+ t cells cyclin e1 cdk2 pair promoting g1 s progression also decreased prmt5 inhibition phosphorylation retinoblastoma sjl mouse relapsingremitting model ms highest prmt5 expression central nervous systeminfiltrating cells corresponded peak relapse timepoints prmt5 expression also positively correlated increasing cd4 th cell composition disease severity cyclin e1 expression data indicate prmt5 promotes g1 s cell cycle progression suggest effect influences disease severity progression animal model ms modulating prmt5 levels may useful controlling t cell expansion t cellmediated diseases including mspmid34168658 pmcpmc8217861 doi103389 fimmu2021695947,0.0
perinatal depression anxiety women multiple sclerosis populationbased cohort study neurology 2021 apr 21101212 wnl0000000000012062 doi 101212 wnl0000000000012062 online ahead printabstractobjective assess occurrence perinatal depression anxiety women diagnosis multiple sclerosis ms methods 114 629 pregnant women included norwegian mother father child cohort study 19992008 assessed depression anxiety questionnaires pregnancy women ms identified national health registries hospital records grouped 1 ms diagnosed pregnancy n 140 ms diagnosed pregnancy 2 symptom onset pregnancy n 98 3 symptom onset pregnancy n 308 thirtyfive women diagnosed ms postpartum period reference group n 111 627 consisted women without msresults women ms diagnosed pregnancy adjusted odds ratio 20 95 confidence interval 1231 depression third trimester risk factors adverse socioeconomic factors history psychiatric disease physical sexual abuse risk anxiety increased women diagnosed ms postpartum period especially high risk postpartum depression women ms symptom onset within 5 years pregnancy increased risk depression anxiety pregnancy whereas women 5 years symptom onset notconclusion women diagnosed ms increased risk perinatal depression women ms symptom onset within 5 years pregnancy increased risk depression anxiety pregnancypmid33883236 doi101212 wnl0000000000012062,0.0
memory b cells multiple sclerosis emerging players disease pathogenesis front immunol 2021 jun 8 12676686 doi 103389 fimmu2021676686 ecollection 2021abstractmultiple sclerosis ms inflammatory demyelinating disease central nervous system thought primarily driven t cells b cells emerging central players ms immunopathogenesis interest multiple b cell phenotypes ms expanded following efficacy b celldepleting agents targeting cd20 relapsingremitting ms inflammatory primary progressive ms patients interestingly therapies primarily target nonantibody secreting cells emerging studies seek explore b cell functions beyond antibodymediated roles including cytokine production antigen presentation ectopic folliclelike aggregate formation importantly memory b cells bmem rising key b cell phenotype investigate ms due antigenexperience increased lifespan rapid response stimulation bmem display diverse effector functions including cytokine production antigen presentation serving antigenexperienced precursors antibodysecreting cells review explore cellular molecular processes involved bmem development bmem phenotypes effector functions examine concepts may applied potential role s bmem ms pathogenesis investigate bmem within periphery inside cns compartment focusing bmem phenotypes proposed functions ms animal models finally review current immunomodulatory therapies including b celldirected therapies immunomodulatory therapies modify bmem knowledge may harnessed direct therapeutic strategies mspmid34168647 pmcpmc8217754 doi103389 fimmu2021676686,1.0
epigenetic mechanisms underlying prostate cancer radioresistance abstractradiotherapy rt one mainstay treatments prostate cancer pca highly prevalent neoplasm among males worldwide 30 newly diagnosed pca patients receive rt curative intent however biochemical relapse occurs 2040 advanced pca treated rt either alone combination adjuvanthormonal therapy epigenetic alterations frequently associated molecular variations pca contribute acquisition radioresistant phenotype increased dna damage repair cell cycle deregulation decreases radioresponse pca patients moreover interplay epigenome cell growth pathways extensively described published literature importantly clinical pattern pca ranges indolent tumor aggressive disease discovering specific targetable epigenetic molecules able overcome predict pca radioresistance urgently needed currently histonedeacetylase dnamethyltransferase inhibitors studied classes chromatinmodifying drugs socalled epidrugs within cancer radiosensitization context nonetheless lack reliable validation trials foremost drawback review summarizes major epigenetically induced changes radioresistantlike pca cells describes recently reported targeted epigenetic therapies preclinical clinical settings,0.0
nodal lymphoplasmacytic lymphoma waldenstrom#39 s macroglobulinemia clinicopathological prognostical study zhonghua bing li xue za zhi 2021 jun 8 50 6 592597 doi 103760 cmajcn1121512020120100882abstractobjective study clinicopathological features prognosis nodal lymphoplasmacytic lymphoma waldenstroms macroglobulinemia nlpl wm methods total 19 cases nlpl wm collected may 2009 january 2020 first affiliated hospital zhengzhou university clinicopathologic features immunophenotype ig gene rearrangement biomed2 myd88 l265p mutation status sanger sequencing followup data telephone analyzed results 15 males 4 females median age 61 years range 43 82 years 14 wm five lpl common symptoms weakness fatigue 9 19 b symptoms 11 19 majority patients 16 18 presented systemic multiple lymphadenopathies eighteen patients presented advanced stages stage serum m protein status igm 15 cases igg 1 case iga 1 case nosecretory type 2 cases seventeen patients bone marrow involvement morphologically 19 cases divided two groups typical group 9 cases atypical group 10 cases typical group structures lymph nodes preserved neoplastic cells predominantly plasmacytoid lymphocytes mixed small lymphocytes plasmacytoid lymphocytes plasma cells without proliferation fdc network follicular implantation atypical group tumor showed effaced nodal architecture 5 cases mainly proliferation small lymphocytes 6 cases fdc proliferation follicular implantation 6 cases marginal zone b cell differentiation 4 cases diffuse amyloidosis 1 case hemosiderin deposition 19 cases infiltration fatty tissue 19 cases interstitial sclerosis 9 cases commonly seen groups immunohistochemically neoplastic b cells expressed cd20 cd79 neoplastic plasma cells positive cd38 cd138 mum1 eight cases showed light chain restriction seven detected cases five expressed igm two expressed igg iga respectively four cases expressed cd23 weakly ki67 index 1030 myd88 l265p mutation seen 18 18 cases significant difference clinicopathologic features prognosis two groups p005 median followup time 61 months 11 patients alive eight died 5year survival rate 211 conclusions nlpl wm rare patients usually present advanced stages easily confused small bcell lymphomas plasma cell differentiation especially basing morphologic features alone thus accurate diagnosis nlpl wm requires combination clinical features serum m protein immunohistochemistry bone marrow morphology flow cytometry myd88 l265p mutation status etc prognosis nlpl wm may good studies cases neededpmid34078045 doi103760 cmajcn1121512020120100882,0.0
cannabinoid receptors distribution mouse cortical plasma membrane compartments abstractthe type 1 type 2 cannabinoid receptors cb1 cb2 receptors class g proteincoupled receptors gpcrs activated endogenous lipids called endocannabinoids modulate neuronal excitability synaptic transmission neurons throughout central nervous system cns inflammatory processes throughout body cb1 receptor one abundant gpcrs cns involved many physiological pathophysiological processes including mood appetite nociception cb2 receptor primarily found immunomodulatory cells cns peripheral immune system study isolated lipid raft nonlipid raft fractions plasma membrane pm mouse cortical tissue using cold nonionic detergent sucrose gradient centrifugation study localization cb1 receptor cb2 receptor lipid raft nonlipid raft fractions confirmed flotillin1 caveolin1 transferrin receptor protein biomarkers cb1 receptor cb2 receptor found nonraft compartments inconsistent previous findings cultured cell lines study demonstrates compartmentalization cb1 receptor cb2 receptor cortical tissue warrants investigation cb1 receptor cb2 receptor compartmental distribution various brain regions cell types,0.0
outcomes social classic cognition adults pediatriconset multiple sclerosis abstractbackgroundcognitive impairment affecting classic social domains consistently reported patients multiple sclerosis ms however little known cognitive outcomes particularly social cognition adults pediatriconset multiple sclerosis poms objectivesto compare performance classic social cognitive domains adults poms adultonset ms aoms methodsa group 30 patients poms age onset 18 years compared agematched aoams n30 disease durationmatched aodms n30 patients developed ms age 18 years cognitive performance assessed using brief international cognitive assessment multiple sclerosis bicams theory mind tom testsresultscognitive impairment prevalent poms patients 40 vs 167 p0045 independently age disease duration affecting severely informationprocessing speed visual memory domains statistically significant differences found tom performance patients poms aomswhen analyzing tom performance according age disease onset 15 years 1520 years 20 years patients disease onset 15 years old significantly lower scores tom tests compared groupsconclusionpatients poms prone develop impairment classic cognitive domains tom ability compared aoms patients interference poms critical neurodevelopmental periods specific cognitive domain may explain different outcomes adulthood social classic cognition,0.0
tet1mediated dna hydroxymethylation regulates adult remyelination mice nat commun 2021 jun 7 12 1 3359 doi 101038 s41467021237353abstractthe mechanisms regulating myelin repair adult central nervous system cns unclear identify dna hydroxymethylation catalyzed teneleventranslocation tet enzyme tet1 necessary myelin repair young adults defective old mice constitutive inducible oligodendrocyte lineagespecific ablation tet1 tet2 recapitulate agerelated decline repair demyelinated lesions dna hydroxymethylation transcriptomic analyses identify tet1target adult oligodendrocytes genes regulating neuroglial communication including solute carrier slc gene family among show expression levels na+ k+ cl transporter slc12a2 higher tet1 overexpressing cells lower old tet1 knockout aged mice tet1 mutants also present inefficient myelin repair axomyelinic swellings zebrafish mutants slc12a2b also display swellings cns myelinated axons findings suggest tet1 required adult myelin repair regulation axonmyelin interfacepmid34099715 doi101038 s41467021237353,1.0
glycolysis inhibition induces functional metabolic exhaustion cd4+ t cells type 1 diabetes front immunol 2021 jun 7 12669456 doi 103389 fimmu2021669456 ecollection 2021abstractin type 1 diabetes t1d cd4+ t cells initiate autoimmune attack pancreatic islet cells importantly bioenergetic programs dictate t cell function specific pathways required progression t cell lifecycle activation cd4+ t cells undergo metabolic reprogramming less efficient aerobic glycolysis similarly highly proliferative cancer cells effort limit tumor growth cancer use glycolytic inhibitors successfully employed preclinical clinical studies strategy also utilized suppress t cell responses autoimmune diseases like systemic lupus erythematosus sle multiple sclerosis ms rheumatoid arthritis ra however modulating t cell metabolism context t1d remained understudied therapeutic opportunity study utilized small molecule pfk15 competitive inhibitor rate limiting glycolysis enzyme 6phosphofructo2kinase fructose2 6 biphosphatase 3 pfkfb3 results confirmed pfk15 inhibited glycolysis utilization diabetogenic cd4+ t cells reduced t cell responses cell antigen vitro adoptive transfer model t1d pfk15 treatment delayed diabetes onset 57 animals remaining euglycemic end study period protection due induction hyporesponsive t cell phenotype characterized increased sustained expression checkpoint molecules pd1 lag3 downstream functional metabolic exhaustion glycolysis inhibition terminally exhausted diabetogenic cd4+ t cells irreversible restimulation checkpoint blockade vitro vivo sum results demonstrate novel therapeutic strategy control aberrant t cell responses exploiting metabolic reprogramming cells t1d moreover data presented highlight key role nutrient availability fueling t cell function implications understanding t cell biology chronic infection cancer autoimmunitypmid34163475 pmcpmc8216385 doi103389 fimmu2021669456,0.0
trigeminal neuralgia definitive diagnosis pain tooth extraction site abstractknowing international classification orofacial pain helps pain specialists differentiate types orofacial pain important select best treatment intervention patients based diagnosis part study reviewed article published bmc oral health titled clinical characteristics associated factors trigeminal neuralgia experience addis ababa ethiopia ayele et al ethiopia bmc oral health 20 1 7 2020 patients suffering classical trigeminal neuralgia taking suitable dose carbamazepine gasser ganglion radiofrequency helpful patients complaining trigeminal neuralgia history dental extraction painful region categorized group complex regional pain syndrome type 1 need larger dose carbamazepine anticonvulsant tricyclic agent drugs eg pregabalin doxepin intervention ppg radiofrequency,0.0
oral pulsed therapy relapsing multiple sclerosis cladribine tablets expert opinion issues clinical practice abstractbackgroundoral cladribine first oral pulsed therapy licensed relapsing multiple sclerosis rms three years introduction european market evaluated practical aspects use cladribine tablets incorporating experience gained routine clinical practice realworld studiesmethodsbased structured review process panel nine neurologists experienced ms therapy discussed salient statements regarding use cladribine tables statement level evidence determined according levels evidence recommended centre evidencebased medicine oxford strength expert statement evaluated means linear scale 1 strong rejection 9 strong approval votes collected formalized blinded process consent considered reached least 75 experts agreed particular statement ie voted 79 points linear scale results statements include efficacy early rms risk side effects infections vaccination pregnancy monitoring requirementsconclusionthe consented recommendations summarize practical experience inthe use cladribine tablets realworld setting may provide guidance unanswered questions arising introduction new treatments cladribine tablets,0.0
role b cells primary progressive multiple sclerosis front neurol 2021 jun 7 12680581 doi 103389 fneur2021680581 ecollection 2021abstractthe success ocrelizumab reducing confirmed disability accumulation primary progressive multiple sclerosis ppms via cd20targeted depletion implicates b cells causal agents pathogenesis ppms review explores possible mechanisms b cells contribute disease progression ppms specifically exploring cytokine production antigen presentation antibody synthesis b cells may contribute disease progression ppms cytokine production specifically gmcsf il6 can drive nave tcell differentiation proinflammatory th1 th17 cells b cell production cytokine lt may induce follicular dendritic cell production cxcl13 lead indirectly t b cell infiltration cns contrast production il10 b cells likely induces antiinflammatory effect may play role reducing neuroinflammation ppms therefore reduced production il10 may contribute disease worsening b cells also capable potent antigen presentation may induce proinflammatory tcell differentiation via cognate interactions b cells may also contribute disease activity via antibody synthesis although unlikely benefit ocrelizumab ppms occurs via antibody decrement finally various b cell subsets likely promulgate pro antiinflammatory effects mspmid34163430 pmcpmc8215437 doi103389 fneur2021680581,0.0
inflammation animal model multiple sclerosis leads microrna253p dysregulation associated inhibition pten klf4 iran j allergy asthma immunol 2021 jun 6 20 3 314325 doi 1018502 ijaaiv20i36337abstractperturbed expression micrornas mirs reported different diseases including autoimmune chronic inflammatory disorders study investigated expression mir253p targets central nervous system cns tissue mice experimental autoimmune encephalomyelitis eae also analyzed expression mir25 targets activated macrophages splenocytes eae induced 12week old female c57bl 6 mice using myelin oligodendrocyte glycoprotein 3555 complete freunds adjuvant mog3555 cfa protocol expression mir253p targets well expression inflammatory cytokines analyzed next established primary macrophage cultures well splenocyte cultures evaluated levels mir253p target genes cells following activation lipopolysaccharide lps anticd3 anticd28 antibodies respectively mir253p expression showed strong positive correlation expression tumor necrosis factoralpha tnf interleukin il 1 il6 proinflammatory cytokines expression phosphatase tensin homolog pten krppellike factor 4 klf4 significantly reduced peak disease interestingly pten klf4 expression showed significant negative correlation mir253p analysis mir253p expression lpstreated primary macrophages revealed significant upregulation cells treated 100ng ml lps associated suppressed levels mir253p targets cells however anticd3 anticd28stimulated splenocytes failed show alterations mir253p expression compared vehicletreated cells results indicate mir253p expression likely induced inflammatory mediators autoimmune neuroinflammation upregulation associated decreased levels pten klf4 genes known roles cell cycle regulation inflammationpmid34134453 doi1018502 ijaaiv20i36337,1.0
synuclein pathology parkinson disease activates homeostatic nrf2 antioxidant response abstractcircumstantial evidence points pathological role alphasynuclein asyn gene symbol snca conferred asyn misfolding aggregation parkinson disease pd related synucleinopathies several findings experimental models implicate perturbations tissue homeostatic mechanisms triggered pathological asyn accumulation including impaired redox homeostasis significant contributors pathogenesis pd nuclear factor erythroid 2related factor nrf2 nrf2 recognized master regulator cellular antioxidant response physiological well pathological conditions using immunohistochemical analyses show robust nuclear nrf2 accumulation postmortem pd midbrain detected nrf2 phosphorylation serine residue 40 nuclear active pnrf2 s40 curated gene expression analyses four independent publicly available microarray datasets revealed considerable alterations nrf2responsive genes disease affected regions pd including substantia nigra dorsal motor nucleus vagus locus coeruleus globus pallidus examine putative role pathological asyn accumulation nuclear nrf2 response employed transgenic mouse model synucleionopathy m83 line expressing mutant human a53t asyn manifests widespread asyn pathology phosphorylated asyn s129 nervous system following intramuscular inoculation exogenous fibrillar asyn observed strong immunodetection nuclear nrf2 neuronal populations harboring pasyn s129 found aberrant antioxidant inflammatory gene response affected neuraxis taken together data support notion pathological asyn accumulation impairs redox homeostasis nervous system boosting neuronal antioxidant response potentially promising approach mitigate neurodegeneration pd related diseases,0.0
fingolimodrelated cryptococcal meningoencephalitis immune reconstitution inflammatory syndrome patient multiple sclerosis abstractfingolimod oral medication multiple sclerosis sequesters certain subsets lymphocytes lymph nodes reducing egress blood subsequent cns migration initial multisite randomized phase iii controlled trials found rates infection similar control groups however postmarketing surveillance revealed association several opportunistic infections including cryptococcosis report case fingolimodrelated cryptococcal meningoencephalitis iris drug discontinuation suggest surveillance risk mitigation strategy,0.0
bone marrow mesenchymal stem cells derived exosomes resolve doxorubicininduced chemobrain critical role mirna cargo background doxorubicin dox widely used chemotherapeutic agent can cause neurodegeneration brain leads condition known chemobrain fact chemobrain deteriorating condition adversely affects lives cancer survivors study aimed examine potential therapeutic effects bone marrow mesenchymal stem cells bmscs derived exosomes bmscsexo doxinduced chemobrain rat modelsmethodschemobrain induced exposing rats dox 2 mg kg ip weekly 4 consecutive weeks 48 h last dox dose subset rats supplied either intravenous injection bmscs 1 106 single dose 150 g bmscsexo behavioral tests conducted 7 days post injection rats sacrificed 14 days bmscs bmscsexo injectionresultsbmscs bmscsexo successfully restored doxinduced cognitive behavioral distortion actions mediated via decreasing hippocampal neurodegeneration neural demyelination upregulating neural myelination factors myelin olig2 opalin expression neurotropic growth factors bdnf fgf2 synaptic factors synaptophysin fractalkine receptor expression cx3cr1 halting neurodegeneration doxinduced chemobrain achieved epigenetic induction key factors wnt catenin hedgehog signaling pathways mediated primarily abundant secreted exosomal mirnas mir215p mir125b5p mir199a3p mir243p let7a5p moreover bmscs bmscsexo significantly abrogate inflammatory state il6 tnf apoptotic state bax bcl2 astrocyte microglia activation gfap iba1 doxinduced chemobrain significant increase antioxidant mediators gsh gpx sod activity conclusionsbmscs derived exosomes offer neuroprotection doxinduced chemobrain via genetic epigenetic abrogation hippocampal neurodegeneration modulating wnt catenin hedgehog signaling pathways reducing inflammatory apoptotic oxidative stress stategraphical abstractproposed mechanisms protective effects bone marrow stem cells bmscs exosomes bmscsexo doxorubicin dox induced chemobrain blue arrows induce red arrows inhibit,1.0
association premature ovarian insufficiency gut microbiota background premature ovarian insufficiency poi characterized impairment ovarian function continuum age 40 years poi affected multiple factors considering new insights recent gut microbiome studies study aimed investigate relationship gut microbial community structure poimethodssubjects recruited shenzhen maternity child healthcare hospital fecal microbial community profiles healthy women n 18 women poi n 35 analyzed using 16s rrna gene sequencing based illumina novaseq platformresultscompared controls serum levels fsh lh t fsh lh ratio significantly increased women poi whereas e2 amh decreased significantly higher weighted unifrac value observed poi women compared healthy women phylum firmicutes genera bulleidia faecalibacterium abundant healthy women phylum bacteroidetes genera butyricimonas dorea lachnobacterium sutterella enriched significantly women poi moreover alterations gut microbiome women poi closely related fsh lh e2 amh level fsh lh ratioconclusionswomen poi altered microbial profiles gut microbiome associated serum hormones levels results will shed new light pathogenesis treatment poi,0.0
brain gray matter astrogliaspecific connexin 43 ablation attenuates spinal cord inflammatory demyelination background brain astroglia activated preceding onset experimental autoimmune encephalomyelitis eae animal model multiple sclerosis ms characterized effects brain astroglia spinal cord inflammation focusing astroglial connexin cx 43 recently reported cx43 critical role regulating neuroinflammationmethodsbecause glutamate aspartate transporter glast + astroglia enriched brain gray matter generated cx43fl fl glastcreert2 + mice brain gray matter astrogliaspecific cx43 conditional knockouts cx43 icko eae induced immunization myelin oligodendroglia glycoprotein mog 3555 peptide 10 days tamoxifen injection cx43fl fl mice used controlsresultsacute chronic eae signs significantly milder cx43 icko mice controls whereas splenocyte mogspecific responses unaltered histologically cx43 icko mice showed significantly less demyelination fewer cd45+ infiltrating immunocytes including f4 80+ macrophages iba1+ microglia spinal cord controls microarray analysis whole cerebellum revealed marked upregulation antiinflammatory a2specific astroglia gene sets preimmunized phase decreased proinflammatory a1specific panreactive astroglial gene expression onset phase cx43 icko mice compared controls astroglia expressing c3 representative a1 marker significantly decreased cerebrum cerebellum spinal cord cx43 icko mice compared controls peak phase isolated cx43 icko spinal microglia showed antiinflammatory less proinflammatory gene expression control microglia preimmunized phase particular microglial expression ccl2 ccl5 ccl7 ccl8 preimmunized phase cxcl9 peak phase lower cx43 icko controls spinal microglia circularity significantly lower cx43 icko controls peak phase significantly lower interleukin il 6 interferon il10 levels present cerebrospinal fluid cx43 icko mice onset phase compared controlsconclusionsthe ablation cx43 brain gray matter astroglia attenuates eae promoting astroglia toward antiinflammatory phenotype suppressing proinflammatory activation spinal microglia partly depressed cerebrospinal fluid proinflammatory cytokine chemokine levels brain astroglial cx43 might novel therapeutic target ms,1.0
bmscderived extracellular vesicles intervened pathogenic changes scleroderma mice mirnas background systemic sclerosis ssc disease features severe fibrosis skin lacks effective therapy bone marrow mesenchymal stem cell bmsc derived extracellular vesicles evs potential stem cellbased tools treatment sscmethodsbmscs isolated bone marrow mice identified surface markers according multilineage differentiation evs isolated bmsc culture medium ultracentrifugation identified nanosight ns300 particle size analyzer transmission electron microscopy tem western blot micrornas mirnas bmscderived evs bmscevs studied via mirna sequencing mirnaseq bioinformatic analysis ssc mouse model established via subcutaneous bleomycin blm injection mice treated bmscs bmscderived evs skin tissues dissociated analyzed staining rna sequencing rnaseq western blot immunohistochemical stainingresultsevident pathological changes like fibrosis inflammation induced skin blmtreated mice bmscs bmscevs effectively intervened pathological manifestations disease processes similar way effects bmscevs found caused mirnas carried proven involved regulating proliferation differentiation multiple cell types multiple evrelated biological processes furthermore tgf1positive cells smapositive myofibroblasts significantly increased scleroderma skin blmtreated mice evidently reduced scleroderma skin evtreated ssc group addition numbers mast cells infiltrating macrophages lymphocytes evidently increased skin blmtreated mice significantly reduced ev treatment line observations significantly higher mrna levels inflammatory cytokines il6 il10 tnf ssc mice control mice levels decreased following ev treatment bioinformatics analysis tgf wnt signaling pathways revealed closely involved pathogenic changes seen mouse ssc pathways therapeutic targets treating diseaseconclusionsbmscderived evs developed potential therapy treating skin dysfunction ssc especially considering show similar efficacy bmscs fewer developmental regulatory requirements cell therapy effects evs generated mirnas carry alleviate ssc pathogenic changes regulating wnt tgf signaling pathways,0.0
vitro vivo tenocyteprotective effectiveness dehydroepiandrosterone high glucoseinduced oxidative stress background dehydroepiandrosterone dhea adrenal steroid protective role diabetes study aimed investigate vitro vivo protective effects dhea high glucoseinduced oxidative stress tenocytes tendonsmethodstenocytes normal spraguedawley rats cultured lowglucose lg highglucose hg medium without dhea experimental groups control group lg without dhea lg dhea hg without dhea hg dhea reactive oxygen species ros production apoptosis messenger rna mrna expression nadph oxidase nox 1 4 interleukin6 il6 determined diabetic rats divided control group dheainjected group dhea group nox1 nox4 protein expression mrna expression nox1 nox4 il6 matrix metalloproteinase mmp 2 tissue inhibitors matrix metalloproteinase timp 2 type iii collagens achilles tendon determinedresultsin rat tenocytes dhea decreased expression nox1 il6 ros accumulation apoptotic cells diabetic rat achilles tendon nox1 protein expression mrna expression nox1 il6 mmp2 timp2 type iii collagen significantly lower type collagen expression significantly higher dhea group control groupconclusionsdhea showed antioxidant antiinflammatory effects vitro vivo moreover dhea improved tendon matrix synthesis turnover affected hyperglycemic conditions dhea potential preventive drug diabetic tendinopathy,1.0
encefalomielitis aguda diseminada simulando enfermedad cerebrovascular en un adolescente summaryacute disseminated encephalomyelitis adem lowprevalence demyelinating disease central nervous system cns predominance presentation pediatric populationto describe review clinical presentation patient adem diagnostic process therapeutic management according available evidencea 17yearold male adolescent 2week history highintensity rightsided headache stitching type subsequent acute multifocal neurological compromise encephalopathy hemiparesis diplopia contrastenhanced brain resonance study evidence hyperintense lesions level stem cerebellum basal ganglia asymmetric unilateral acute following vascular path posteroinferior cerebellar artery pica without restriction diffusion changes adc map initial suspicion cerebrovascular event cvd made studying normal angioresonance diagnostic aids negative cardioembolic causes thrombophilias considering lesions suggest changes ischemic origin demyelinating management methylprednisolone pulses resolution hemiparesis encephalopathy initiated 18month followup patient presented new clinical radiological eventsadem infrequent pathology pediatric age diagnosis based clinic magnetic resonance imaging findings clinical presentation may nonspecific case simulate cerebrovascular disease treatment based immunomodulatory treatment mainly corticosteroids favorable recovery rate previously reported serieskeywords encephalomyelitis acute disseminated brain diseases pediatrics mesh,1.0
atraumatic thoracic spinal fracture mimicking herpes zoster neuralgia case report background intercostal neuralgia common patients herpes zoster might initial symptom serious diseases atraumatic spinal fracture may lead serious consequences diagnosed treated early severe intercostal neuralgia rarely reported first symptom ankylosing spondylitis atraumatic vertebral fracturescase presentationa 70yearold chinese han man previously diagnosed ankylosing spondylitis presented hospital intense intercostal pain without trauma patient initially suspected herpes zoster neuralgia however subsequently experienced numbness weakness lower limbs well constipation thoracic vertebral fracture compression spinal cord detected magnetic resonance imaging underwent emergency posterior thoracic spinal canal decompression intercostal neuralgia relieved surgery spinal tuberculosis tumors later excluded pathological examination followup results 6month postoperative followup showed weakness numbness left lower limb significantly improved urinary function recoveredconclusionspatients ankylosing spondylitis develop atraumatic spinal fractures severe intercostal neuralgia early indicator spinal fractures spinal magnetic resonance imaging crucial diagnosis,0.0
comparative study teriflunomide dimethyl fumarate within swedish ms registry abstractbackgroundteriflunomide dimethyl fumarate dmf firstline diseasemodifying treatments multiple sclerosis similar labels used comparable populationsobjectivesthe objective study compare effectiveness persistence teriflunomide dmf swedish realworld settingmethodsall relapsingremitting multiple sclerosis rrms patients swedish ms registry initiating teriflunomide dmf included analysis primary endpoint treatment persistence propensity score matching used adjust comparisons baseline confoundersresultsa total 353 teriflunomide patients successfully matched 353 dmf difference rate overall treatment discontinuation treatment group across entire observation period hazard ratio hr 112 95 confidence interval ci 091139 p 0277 reference teriflunomide annualised relapse rate arr comparable p 0237 dmf 007 95 ci 005010 teriflunomide 009 95 ci 007012 difference time first ontreatment relapse hr 078 95 ci 050121 disability progression hr 055 95 ci 027112 confirmed improvement hr 117 95 ci 057236 conclusionthis populationbased realworld study reports similarities treatment persistence clinical effectiveness quality life outcomes teriflunomide dimethyl fumarate,0.0
clinical ethics consultation neurology case series background concept clinical ethics consultation cecs implemented provide support ethical controversies clinical settings offered least every second hospital germany neurological disorders often require complex decisionmaking aims study determine situations lead cec neurology investigate influence individual patients wishes recommendationmethodsstandardised cec protocols years 2011 2017 university hospitals goettingen jena retrospectively surveyed contents categorised along existing protocol templates cec scenarios subsequently paraphrased reduced significant meaningsresults27 cec scenarios facilitated various professional disciplines reviewed stroke frequent underlying condition nearly patients able consent mostly relatives acted representatives health advocates 67 cases sense conflict triggered cec 33 sense uncertainty reason cec request 21 cec scenarios recommendation reached consensus parties involved 59 cases decision made continue medical therapy seven cases patients wishes led limitation therapy just two cases decision made primarily relying patients best interest 13 cases valid advance directive led respective therapeutic consequencesconclusionscec feasible consensusfinding conflicts also situations therapeutic uncertainty neurology special importance patients wishes decisionmaking neurology however cases advance directives precise specific enough sufficient decisive weight therapeutic decisionmaking,0.0
malaysian delphi consensus managing knee osteoarthritis background 2013 malaysian clinical practice guidelines management osteoarthritis oa recommend linear stepup approach manage knee oa however patients knee oa often require multimodal approach address oarelated pain symptoms functional limitations consensus aimed provide doctors updated set evidencebased clinical experienceguided recommendations manage knee oamethodsa multispeciality expert panel consisting nine malaysian physicians different healthcare settings manage diverse oa patient population convened using combination adapte process modified delphi method panel reviewed current evidence management knee oa synthesised set nine recommendations management knee oa supported algorithm summarises consensus core messagesresultsa multimodal intervention strategy mainstay oa management choice single multimodal intervention may vary course disease overall nonpharmacological core treatment set patient education weight loss exercise recommended patients pharmacotherapy indicated symptomatic slowacting drugs osteoarthritis recommended early stage disease can paired physical therapy background treatment concurrent advanced pharmacotherapy includes nonsteroidal antiinflammatory drugs intraarticular injections shortterm weak opioids can considered patients respond sufficiently background treatment patients severe symptomatic knee oa considered knee replacement surgery management begin specific treatments least systemic exposure toxicity choice treatment determined shared decision patients team healthcare providersconclusionsthis consensus presents nine recommendations advocate algorithmic approach management patients living knee oa applicable patients receiving treatment primary tertiary care providers malaysia well countries,0.0
quantification smooth pursuit dysfunction multiple sclerosis abstractbackground smooth pursuit dysfunction common ms rarely quantified may missed exammethods neurofitone smooth pursuit performance measures compared ms n20 healthy control n19 participantsresults compared controls ms patients lower proportion smooth pursuit 063vs 073 p0047 increased directional 101vs 8 p0014 speed noise 43vs 31 sec p0021 reduced initiation acceleration 9683vs 11533 sec2 p0061 significant univariate correlations clinical scores edss t25fw observedconclusion smooth pursuit dysfunction ms can readily quantified distinguishes ms eyes healthy controls,0.0
ifn acts monocytes ameliorate cns autoimmunity inhibiting proinflammatory crosstalk monocytes th cells front immunol 2021 jun 4 12679498 doi 103389 fimmu2021679498 ecollection 2021abstractifn treatment multiple sclerosis ms almost three decades understanding mechanisms underlying beneficial effects remains incomplete shown ms patients increased numbers gmcsf+ th cells circulation ifn therapy reduces numbers gmcsf expression myelinspecific th cells essential development experimental autoimmune encephalomyelitis eae animal model ms findings suggested ifn therapy may function via suppression gmcsf production th cells current study elucidated feedback loop monocytes th cells amplifies autoimmune neuroinflammation found ifn therapy ameliorates central nervous system cns autoimmunity inhibiting proinflammatory loop ifn suppressed gmcsf production th cells indirectly acting monocytes ifn signaling monocytes required eae suppression ifn increased il10 expression monocytes il10 required suppressive effects ifn ifn treatment suppressed il1 expression monocytes cns mice eae gmcsf th cells induced il1 production monocytes positive feedback loop il1 augmented gmcsf production th cells addition gmcsf tnf fasl expression th cells also necessary il1 production monocyte ifn inhibited gmcsf tnf fasl expression th cells suppress il1 secretion monocytes overall study describes positive feedback loop involving several th cell monocytederived molecules ifn actions monocytes disrupting proinflammatory looppmid34149716 pmcpmc8213026 doi103389 fimmu2021679498,1.0
single patient reported outcome measure acquired brain injury multiple sclerosis amp amp parkinson#39 s disease plos one 2021 jun 4 16 6 e0251484 doi 101371 journalpone0251484 ecollection 2021abstractobjective determine psychometric properties promis10 standard stroke question set international consortium health outcome measures presented new 15item patient related outcome pro patients acquired brain injury abi multiple sclerosis ms parkinsons disease pd methods eight centre uk wide crosssectional study approached patients routine followup complete diseasespecific instrument european brain injury questionnaire multiple sclerosis impact scale parkinsons disease questionnaire general health questionnaire quality life measure eq5d pro validated pro using factor analysis define latent construct domains calculated internal consistency cronbachs construct validity correlation results 340 patients abi n 91 median age 551 41 female ms n 99 age 589 69 pd n 150 age 745 40 factor analysis suggested pro offered three domains physical health functionalitycapacity mental health factors correlated strongly three diseasespecific instruments overall pro large correlation eq5d correlation08 offering good construct validity excellent internal consistency 089 interpretation pro offered promising psychometric properties used place disease specific questionnaires patients abi ms pd pro three construct domains describing patients mental health physical health functionalcapacity may used routine clinical practice pro offered relevance three separate neurological conditions generalisability across conditions increasing utilitypmid34086698 doi101371 journalpone0251484,0.0
mental health people multiple sclerosis covid19 outbreak prospective cohort crosssectional casecontrol study uk ms register backgroundpeople ms pwms higher rates anxiety depression general population covid19 pandemic placing higher risk experiencing poor psychological wellbeing pandemicobjectiveto assess mental health social lifestyle determinants pwms first wave outbreak united kingdommethodsthis communitybased prospective longitudinal cohort crosssectional casecontrol online questionnaire study includes 2010 pwms uk ms register 380 people without msresultsthe hospital anxiety depression scale scores pwms anxiety depression outbreak change previous year pwms likely anxiety using general anxiety disorder7 depression using patient health questionnaire9 controls outbreak 214 95 ci 158291 pwms felt lonelier 137 95 ci 104180 reported worse social support 190 95 ci 118307 reported worsened exercise habits 165 95 ci 118232 outbreak controlsconclusionearly pandemic pwms remained higher risk experiencing anxiety depression general population important multidisciplinary teams improve support wellbeing pwms vulnerable negative effects pandemic lifestyle social support,0.0
cryoem effect structural biology neurodegenerative disease aggregates j neuropathol exp neurol 2021 may 10nlab039 doi 101093 jnen nlab039 online ahead printabstractneurogenerative diseases characterized diverse protein aggregates variety microscopic morphologic features although ultrastructural studies human neurodegenerative disease tissues conducted since 1960s recently nearatomic resolution structures neurodegenerative disease aggregates described solidstate nuclear magnetic resonance spectroscopy xray crystallography provided nearatomic resolution information vitro aggregates pose logistical challenges resolving structure aggregates derived human tissues recent advances cryoelectron microscopy cryoem provided means nearatomic resolution structures tau amyloid synuclein syn transactive response element dnabinding protein 43 kda tdp43 aggregates variety diseases importantly vitro aggregate structures recapitulate ex vivo aggregate structures ex vivo tau aggregate structures indicate individual tauopathies consistent aggregate structure unique tauopathies syn structures show even within disease aggregate heterogeneity may correlate disease course ex vivo structures also provided insight posttranslational modifications may relate aggregate structure though less cryoem data human tissuederived tdp43 initial structural studies provide basis future endeavors review highlights structural variations across neurodegenerative diseases reveals fundamental differences experimental systems human tissue derived protein inclusionspmid33970243 doi101093 jnen nlab039,0.0
bilateral fingolimodassociated macular oedema development cataract surgery bmj case rep 2021 jun 4 14 6 e240562 doi 101136 bcr2020240562abstractpostoperative cystoid macular oedema cmo recognised complication cataract surgery occurring around 15 cases generally managed topical steroids nonsteroidal antiinflammatory medications present case patient developed bilateral sequential cmo following bilateral sequential cataract surgery nonresponsive topical therapy worsened following subtenons administration steroid patient took fingolimod multiple sclerosis prior period cataract surgery known result development macular oedema patients fingolimod cessation oedema resolved period 5 months good visual recovery present case inform cataract surgeons risk fingolimodassociated macular oedema patients undergoing cataract surgery inform neurologists potential need adjust treatment patients undergoing cataract surgerypmid34088686 doi101136 bcr2020240562,0.0
defining caprin1 interactome unstressed stressed conditions j proteome res 2021 may 3 doi 101021 acsjproteome1c00016 online ahead printabstractcytoplasmic stress granules sgs dynamic foci containing translationally arrested mrna rnabinding proteins rbps form response variety cellular stressors debated sgs may evolve cytoplasmic inclusions observed many neurodegenerative diseases recent studies examined sg proteome interrogating interactome g3bp1 however widely accepted multiple baits required capture full sg proteome gain insight sg proteome employed immunoprecipitation coupled mass spectrometry endogenous caprin1 rbp implicated mrnp granules overall identified 1543 proteins interact caprin1 interactors stressed conditions primarily annotated ribosome spliceosome rna transport pathways validated four caprin1 interactors localized arseniteinduced sgs ankhd1 talin1 gemin5 snrnp200 also validated stressinduced interactions shsy5y cells determined snrnp200 also associated osmotic thermalinduced sgs finally identified snrnp200 cytoplasmic aggregates amyotrophic lateral sclerosis als spinal cord motor cortex collectively findings provide first description caprin1 protein interactome identify novel cytoplasmic sg components reveal sg protein cytoplasmic aggregates als patient neurons proteomic data collected study available via proteomexchange identifier pxd023271pmid33939924 doi101021 acsjproteome1c00016,0.0
latent gammaherpesvirus exacerbates arthritis modification ageassociated b cells elife 2021 jun 3 10e67024 doi 107554 elife67024 online ahead printabstractepsteinbarr virus ebv infection associated rheumatoid arthritis ra adults though nature relationship remains unknown herein examine contribution viral infection severity arthritis mice provide first evidence latent gammaherpesvirus infection enhances clinical arthritis modeling ebvs role ra mice latently infected murine analog ebv gammaherpesvirus 68 ghv68 develop severe collageninduced arthritis th1skewed immune profile reminiscent human disease demonstrate disease enhancement requires viral latency due active virus stimulation immune response ageassociated b cells abcs associated several human autoimmune diseases including arthritis though contribution disease well understood using abc knockout mice provide first evidence abcs mechanistically required viral enhancement disease thereby establishing abcs impacted latent gammaherpesvirus infection provoke arthritispmid34080972 doi107554 elife67024,0.0
native t1 mapping extracellular volume fraction differentiation myocardial diseases normal cmr controls routine clinical practice background study aimed determine native t1 extracellular volume fraction ecv distinct types myocardial disease including amyloidosis dilated cardiomyopathy dcm hypertrophic cardiomyopathy hcm myocarditis coronary artery disease cad compared controlsmethods retrospectively enrolled patients distinct types myocardial disease cad patients control group known heart disease negative cmr study underwent 30 tesla cmr routine t1 mapping region interest roi drawn myocardium mid left ventricular lv short axis slice interventricular septum mid lv slice ecv calculated actual hematocrit hct synthetic hct t1 mapping ecv compared myocardial disease controls cad controls diagnostic yield cutoff values assessedresultsa total 1188 patients enrolled average t1 values control group 1304 42 ms septum 1294 37 ms mid lv slice average t1 values patients myocardial disease cad significantly higher controls 1441 72 1349 59 1345 59 1355 56 1328 54 ms septum amyloidosis dcm hcm myocarditis cad native t1 mid lv level ecv septum mid lv actual synthetic hct patients myocardial disease cad significantly higher controlsconclusionsalthough native t1 ecv patients cardiomyopathy cad significantly higher controls values overlapped greatest clinical utilization found amyloidosis group,0.0
igg antibody titers sarscov2 reveal distinct efficacy multiple sclerosismodifying therapies curtail lymphocyte compartments ther adv neurol disord 2021 jun 3 1417562864211022109 doi 101177 17562864211022109 ecollection 2021no abstractpmid34158836 pmcpmc8182216 doi101177 17562864211022109,0.0
synthesis 4 4 arylmethylene bis 3methyl1phenyl1hpyrazol5ols evaluation antioxidant anticancer activities background pyrazoles attracted particular attention due diverse biological activities associated heterocyclic system shown cytotoxic several human cell lines several drugs currently market heterocycle key structural motif approved treatment different types cancerresults4 4 arylmethylene bis 1hpyrazol5ols derivatives 3aq synthetized three components reaction 3methyl1phenyl5pyrazolone 1 various benzaldehydes 2 catalyzed sodium acetate room temperature structures synthesized compounds characterized physicochemical properties spectral means ir nmr evaluated radical scavenging activity dpph assay tested vitro colorectal rko carcinoma cells order determine cytotoxic properties 4 4 arylmethylene bis 1hpyrazol5ols derivatives 3aq synthetized high excellent yield pure products isolated simple filtration compounds good radical scavenging activity half active ascorbic acid used standardconclusionseveral derivatives proved cytotoxic rko cell line particular compound 3i proved potent scavenger ic50 62 06 m exhibited ic50 99 11 m rko cell autophagy proteins activated survival mechanism whereas predominant pathway death p53mediated apoptosis,0.0
speed smoothness gait reacts rehabilitation multiple sclerosis mult scler int 2021 jun 3 20215589562 doi 101155 2021 5589562 ecollection 2021abstractintroduction improved gait one leading therapy goals multiple sclerosis plethora clinical timed trials stateoftheart technologybased approaches available assess gait performanceobjectives examine aspects gait react inpatient rehabilitation ms parameters best assesseddesign longitudinal study examined performance 76 patients ms shed light factors influencing gait associations tests reaction inpatient rehabilitation average time span 16 d setting private specialist clinic inpatient neurorehabilitation main outcome measures clinical walk tests timed 25foot walk test normal pace maximum pace 10 m 6 min imubased measures movement smoothnessresults gait parameters strongly intercorrelated p 005 model multiple linear regression 6mwt revealed short distance velocity 10 m movement smoothness predictors strong model r 2 adjusted 075 p 001 second model natural pace short distance movement smoothness almost equally strong r 2 adjusted 071 p 001 patients improved walking speed p 001 smoothness p 008012 course rehabilitationconclusions since able observe improvements smoothness gait conclude rehabilitation programs adapted patients physiological capacities order allow improvements smoothness gait externally valid gait capacity 6mwt predicted single walk 10 s natural pacepmid34123427 pmcpmc8192191 doi101155 2021 5589562,0.0
pathology neurovascular unit leukodystrophies abstractthe bloodbrain barrier dynamic endothelial cell barrier brain microvasculature separates blood brain parenchyma specialized brain endothelial cells astrocytes neurons microglia pericytes together compose neurovascular unit interact maintain bloodbrain barrier function disturbed brain barrier function reported common neurological disorders may play role disease pathogenesis however comprehensive overview neurovascular unit affected wide range rare disorders lacking aim provide insights neuropathology neurovascular unit leukodystrophies unravel potential pathogenic role diseases leukodystrophies monogenic disorders white matter due defects structural components single leukodystrophies exceedingly rare availability human tissue unique expression selective neurovascular unit markers claudin5 zona occludens 1 laminin pdgfr aquaporin4 dystroglycan investigated eight different leukodystrophies using immunohistochemistry observed tight junction rearrangements indicative endothelial dysfunction five eight assessed leukodystrophies different origin altered aquaporin4 distribution aquaporin4 redistribution indicates general astrocytic dysfunction leukodystrophies even directly related astrocytic pathology without prominent reactive astrogliosis findings provide evidence dysfunction orchestration neurovascular unit leukodystrophies contribute better understanding underlying disease mechanism,0.0
rapid decline cardiac function diabetic patients calcified coronary artery disease undergoing hemodialysis two case reports background clinical symptoms patients dialysis match signs coronary disease progression making prediction true progression medical condition clinical settings difficult emergency concomitant surgeries significant risk factors mortality following openheart surgery patients hemodialysiscase presentation report two cases successful coronary artery bypass grafting cabg patients dialysis history cardiac surgery first case describes 65yearold woman undergone aortic valve replacement 2 years ago hospitalized urgently sudden decline heart function hypotension moderate mitral regurgitation right ventricular pressure 66 mmhg poor left ventricular function left ventricular ejection fraction lvef 40 cineangiography revealed increase rate stenosis left main trunk 25 99 admission addition 100 occlusion proximal left anterior descending artery lad 99 stenosis proximal left circumflex artery lcx inserted intraaortic balloon pump preoperatively performed emergency surgery euro ii risk score 617 society thoracic surgeons sts risk score 563 second case described 78yearold man undergone surgery left atrial myxoma 4 years ago hospitalized urgently due dyspnea chest discomfort lvef 44 euro ii risk score 407 sts risk score 332 cineangiography revealed increase rate stenosis proximal lad 25 4 years ago 90 admission addition 99 stenosis proximal lcx 95 stenosis posterolateral branch lcx patients underwent emergency cabg due unstable hemodynamics decreased left ventricular function despite regular dialysis surgeries successful patients discharged without complicationsconclusionsin patients multiple comorbidities undergo dialysis treatment calcified lesions coronary arteries can progress severely rapidly without symptoms including chest pain close outpatient management involving nephrologists cardiovascular team necessary patients dialysis,0.0
safety efficacy ayurvedic interventions yoga long term effects covid19 structured summary study protocol randomized controlled trial abstractobjectivesprimary objective assess efficacy ayurveda interventions yoga rehabilitation covid19 cases suffering long term effects covid 19 compared rehabilitation selfmanagement covid19 related illnesssecondary objective assess safety ayurvedic interventions cases suffering long term effects covid 19trial designmulticentric randomized controlled parallel group openlabel exploratory study study duration 9 months intervention period 90 days day enrolment participantparticipantspatients either sex 18 60 years ambulatory willing participate history 4 weeks positive rtpcr covid19 igm antibodies positivity sars cov2 negative rtpcr covid19 time screening will considered eligible enrolment study critically ill patients ards acute respiratory distress syndrome requiring invasive respiratory support intensive care unit known case malignancy immunecompromised state eg hiv diabetes mellitus active pulmonary tuberculosis past history chronic respiratory disease motor neuron disease multiple sclerosis stroke impaired cognition atrial fibrillation acute coronary syndrome myocardial infarction severe arrhythmia concurrent serious hepatic disease renal disease pregnant lactating women patients immunosuppressive medications history hypersensitivity trial drugs ingredients depressive illness covid19 diagnosed psychotic illnesses substance dependence alcoholism will excludedthe trial will conducted two medical colleges maharashtra indiaintervention comparatorintervention arm groupi ayurveda interventions including agastya haritaki six gram ashwagandha tablet 500 mg twice daily orally meals warm water two sessions yoga morning 30 minutes evening 15 minutes daily 90 days per postcovid19 care protocol provided national clinical management protocol based ayurveda yoga management covid19 published ministry ayush government indiacomparator arm groupii rehabilitation selfmanagement covid19 related illness 90 daysthe trial drugs procured gmp certified pharmaceutical companymain outcomesprimary outcome change respiratory function assessed san diego shortness breath questionnaire 6minutes walk test pulmonary function testsecondary outcomes change highresolution computed tomography hrct chest change fatigue score assessed modified fatigue impact scale change anxiety score assessed hospital anxiety depression scale score change sleep quality assessed pittsburgh sleep quality index change quality life assessed cov19qol scale safety interventions will assessed comparing hematological biochemical investigations intervention period adverse event adverse drug reaction timelines outcome assessmentsubjective parameters clinical assessment will assessed baseline 15th day 30th day 60th day 90th day laboratory parameters cbc lft kft hba1c hscrp ddimer pulmonary function test hrct chest will done baseline completion study period ie 90th dayrandomisationstatistical package social sciences spss version 150 used generate random number sequences participants will randomized two study groups ratio 11blinding masking study openlabel design however outcome assessor will kept blinded regarding study group allocation participantsnumbers randomised sample size sample sizethe sample size study calculated assuming improvement 6minutes walk test 40 meter group change 10 meter group ii standard deviation 50 meter based results previous studies 95 confidence level 005 80 power expecting dropout rate 20 number participants enrolled study approximately 55 group hence total 110 participants will enrolled trial study sitetrial statusparticipants recruitment started 1st may 2021 anticipated end recruitment august 2021 protocol number ccras01 protocol version number 11 13th january 2021trial registrationthe trial prospectively registered clinical trial registry india ctri 03rd march 2021 ctri 2021 03 031686 full protocolthe full protocol attached additional file accessible journal website additional file 1 communication serves summary key elements full protocol,0.0
correlations macrophage microglial activation marker strem2 measures tcell activation neuroaxonal damage disease severity multiple sclerosis mult scler j exp transl clin 2021 jun 3 7 2 20552173211019772 doi 101177 20552173211019772 ecollection 2021 aprjunabstractbackground soluble triggering receptor expressed myeloid cells2 strem2 marker macrophage microglial activation increased cerebrospinal fluid csf multiple sclerosis ms objective determine relationships among strem2 t cell activation neuroaxonal damage clinical features msmethods enzymelinked immunosorbent assays used measure levels strem2 soluble cd27 scd27 marker t cell activation neurofilament light chain nfl phosphorylated neurofilament heavy chain pnfh csf 42 patients ms including nine clinically isolated syndrome 15 patients neurological diseases ond serum 164 patients ms 87 patients ond 62 healthy controlsresults strem2 significantly elevated csf p 0012 serum ms compared ond ms csf strem2 correlated positively csf scd27 p 0005 csf nfl p 00001 csf pnfh p 00006 expanded disability status scale edss score p 00079 ms severity score msss p 00006 conclusion ms level strem2 csf related measures t cell activation scd27 neuroaxonal damage nfl pnfh disability edss disease severity msss pmid34158970 pmcpmc8182190 doi101177 20552173211019772,0.0
correspondence humoral immune response covid19 mrna vaccine patients multiple sclerosis treated highefficacy diseasemodifying therapies ther adv neurol disord 2021 jun 3 1417562864211022581 doi 101177 17562864211022581 ecollection 2021no abstractpmid34158837 pmcpmc8182197 doi101177 17562864211022581,0.0
atg7 deficiency microglia drives altered transcriptomic profile associated impaired neuroinflammatory response abstractmicroglia resident immunocompetent cells central nervous system can display range reaction states thereby exhibit distinct biological functions across development adulthood disease conditions distinct gene expression profiles reported define microglial reaction states hence identification modulators selective microglial transcriptomic signature potential regulate unique microglial function gained interest report identification atg7 autophagyrelated 7 selective modulator nfbdependent transcriptional program controlling proinflammatory response microglia also uncover microglial atg7deficiency associated reduced microgliamediated neurotoxicity thus loss biological function associated proinflammatory microglial reactive state show atg7deficiency microglia impact ability respond alternative stimulus one driving towards antiinflammatory tumor supportive phenotype identification distinct regulators atg7 controlling specific microglial transcriptional programs lead developing novel therapeutic strategies aiming manipulate selected microglial phenotypes instead whole microglial population associated several pitfalls,1.0
baclofen therapeutics toxicity withdrawal narrative review sage open med 2021 jun 3 920503121211022197 doi 101177 20503121211022197 ecollection 2021abstractbaclofen effective therapeutic treatment spasticity related multiple sclerosis spinal cord injuries spinal cord pathologies increasingly used offlabel management several disorders including musculoskeletal pain gastroesophageal reflux disease alcohol use disorder baclofen therapy associated potential complications including lifethreatening toxicity withdrawal syndrome disorders require prompt recognition high index suspicion complications can develop following administration either oral intrathecal baclofen risk greater intrathecal route management baclofen toxicity largely supportive baclofen withdrawal syndrome effectively treated reinitiation supplementation baclofen dosing administration pharmacologic adjuncts may required effectively treat associated withdrawal symptoms narrative review provides overview historical emerging uses baclofen offers practical dosing recommendations oral intrathecal routes administration reviews diagnosis management baclofen toxicity withdrawalpmid34158937 pmcpmc8182184 doi101177 20503121211022197,0.0
heterogeneous human memory ccr6+ t helper17 populations differ tbet cytokine expression activate synovial fibroblasts ifnindependent manner background chronic synovial inflammation important hallmark inflammatory arthritis cells mechanisms involved incompletely understood previously shown ccr6+ memory thelper memth cells synovial fibroblasts sf activate proinflammatory feedforward loop potentially drives persistent synovial inflammation inflammatory arthritis however ccr6+ memth cells heterogeneous population containing th17 th22 th171 cells currently unclear subpopulations drive sf activation targeted study examined individual contribution ccr6+ memth subpopulations sf activation examined ways regulate functionmethodsth17 th22 cxcr3ccr4+ th171 cxcr3+ccr4 dp cxcr3+ccr4+ dn cxcr3ccr4 ccr6+ memth cells sorted pbmc healthy donors treatmentnave early rheumatoid arthritis ra patients cocultured sf ra patients without antiil17a antiifn 1 25 oh 2d3 cultures analyzed rtpcr elisa flow cytometryresultsth17 th22 th171 dp dn cells equally express rorc differ production tbx21 cytokines like il17a ifn despite differences individual ccr6+ memth subpopulations healthy individuals ra patients potent activating sf classical th1 cells sf activation partially inhibited blocking il17a inhibiting ifn tbx21 however active vitamin d inhibited pathogenicity subpopulations leading suppression sf activationconclusionshuman ccr6+ memth cells contain several subpopulations equally express rorc differ tbx21 ifn il17a expression individual th17 subpopulations potent activating sf classical th1 cells ifnindependent manner furthermore data suggest il17a dominant t cellsf activation loop multiple t cell cytokine inhibitor 1 25 oh 2d3 able suppress ccr6+ memth subpopulationdriven sf activation,0.0
innate signaling cns prevents demyelination focal eae model front neurosci 2021 jun 3 15682451 doi 103389 fnins2021682451 ecollection 2021abstractthe pathological hallmark multiple sclerosis ms formation multifocal demyelinating lesions central nervous system cns stimulation innate receptors shown suppress experimental autoimmune encephalomyelitis eae mslike disease mice specifically targeting tolllike receptor 9 tlr9 nodlike receptor 2 nod2 significantly reduced disease severity present work developed novel focal eae model study effect innate signaling demyelinating pathology focal lesions induced stereotactic needle insertion corpus callosum cc mice previously immunized eae resulted focal pathology characterized infiltration demyelination cc find intrathecal delivery mis416 tlr9 nod2 bispecific innate ligand cerebrospinal fluid reduced focal lesions cc associated upregulation type ii interferons interleukin10 arginase1 ccl2 cxcl10 analysis draining cervical lymph nodes showed upregulation type ii interferons interleukin 10 moreover intrathecal mis416 altered composition early cns infiltrates increasing proportions myeloid nk cells reducing t cells lesion site study contributes increased understanding innate immune responses can play protective role turn may lead additional therapeutic strategies prevention treatment demyelinating pathologiespmid34149350 pmcpmc8209300 doi103389 fnins2021682451,1.0
symptom measures pediatric narcolepsy patients review abstractpurposethis study aimed provide summary measures assess narcoleptic symptoms complications pediatric narcolepsy patientsmethodswe searched national center biotechnology information ncbi measures narcoleptic symptoms pediatric patients review conducted relevant questionnaires information mentionedresultsthere two narcolepsyspecific questionnaires narcolepsy severity scale ullanlinna narcolepsy scale neither developed validated pediatric population cataplexy measures studyspecific diaries validated questionnaires excessive daytime sleepiness epworth sleepiness scale frequently used measure excessive daytime sleepiness children nighttime sleep childrens sleep habits questionnaire frequently used depression children depression inventory frequently used attentiondeficit hyperactivity disorder child behavior checklist frequently used quality life kidscreen frequently usedconclusionsat present lack diseasespecific validated questionnaires pediatric narcoleptic patients need can met modifying adjusting existing adult questionnaires developing new questionnaires pediatric narcoleptic patients,0.0
targeted expression myelin autoantigen periphery induces antigenspecific t b cell tolerance ameliorates autoimmune disease front immunol 2021 jun 2 12668487 doi 103389 fimmu2021668487 ecollection 2021abstractthere great interest developing antigenspecific therapeutic approaches treatment autoimmune diseases without compromising normal immune function key challenges control antigenspecific lymphocyte populations contribute pathogenic inflammatory processes provide longterm protection disease relapses show myelin oligodendrocyte glycoprotein mog specific tolerance can established ectopic expression mog immune organs using transgenic mice expressing mogspecific cd4 cd8 b cell receptors show mog expression bone marrow cells results impaired development mogspecific lymphocytes ectopic mog expression also resulted longlasting protection moginduced autoimmunity finding raises hope transplantation autoantigenexpressing bone marrow cells therapeutic strategy specific autoantigendriven autoimmune diseasespmid34149706 pmcpmc8206569 doi103389 fimmu2021668487,1.0
brainstem involvement amyotrophic lateral sclerosis combined structural diffusion tensor mri analysis front neurosci 2021 jun 2 15675444 doi 103389 fnins2021675444 ecollection 2021abstractintroduction brainstem important component pathology amyotrophic lateral sclerosis als although neuroimaging studies shown multiple structural changes als patients studies investigated structural alterations brainstem herein compared brainstem structure patients als healthy controlsmethods total 33 patients als 33 healthy controls recruited study t1weighted diffusion tensor imaging dti acquired 3 tesla magnetic resonance imaging 3t mri scanner volumetric vertexwised approaches implemented assess differences brainstems morphological features two groups atlasbased region interest roi analysis performed compare white matter integrity brainstem two groups additionally correlation analysis used evaluate relationship als clinical characteristics structural featuresresults volumetric analyses showed significant difference subregion volume brainstem als patients healthy controls shape analyses als patients local abnormal surface contraction ventral medulla oblongata ventral pons compared healthy controls als patients showed significantly lower fractional anisotropy fa left corticospinal tract cst bilateral frontopontine tracts fpt brainstem level higher radial diffusivity rd bilateral cst left fpt brainstem level roi analysis dti correlation analysis showed disease severity positively associated fa left cst left fptconclusion findings suggest brainstem als suffers atrophy degenerative processes brainstem may reflect disease severity als findings may helpful understanding potential neural mechanisms alspmid34149349 pmcpmc8206526 doi103389 fnins2021675444,0.0
emerging application nanorobotics artificial intelligence cross bbb advances design controlled maneuvering targeting barriers acs chem neurosci 2021 may 19 doi 101021 acschemneuro1c00087 online ahead printabstractthe bloodbrain barrier bbb prime focus clinicians maintain homeostatic function health deliver theranostics brain cancer number neurological diseases structural hierarchy situ biochemical signaling bbb neurovascular unit primary targets recapitulate vitro modules microengineered perfusion systems development 3d cellular organoid culture given major thrust bbb research neuropharmacology review focus revisiting nanoparticles based bimolecular engineering enable maneuver control target deliver theranostic payloads across cellular bbb nanorobots nanobots subsequently provide brief outline specific case studies addressing payload delivery brain tumor neurological disorders eg alzheimers disease parkinsons disease multiple sclerosis etc addition also address opportunities challenges across nanorobots development design finally address computationally powered machine learning ml tools artificial intelligence ai can partnered robotics predict design next generation nanorobots interact deliver across bbb without causing damage toxicity malfunctions content review references multidisciplinary science clinicians roboticists chemists bioengineers involved cuttingedge pharmaceutical design bbb researchpmid34008957 doi101021 acschemneuro1c00087,0.0
neurological complications pediatric patients sarscov2 infection systematic review literature abstractobjectivesto describe clinical characteristics laboratory tests radiological data outcome pediatric cases sarscov2 infection complicated neurological involvementstudy designa computerized search conducted using pubmed article considered eligible reported data pediatric patient s neurological involvement related sarscov2 infection also described case acute disseminated encephalomyelitis adem 5yearold girl sarscov2 infection case also included systematic reviewresultsfortyfour articles reporting 59 cases neurological manifestations pediatric patients included review 32 59 cases occurred course multisystem inflammatory syndrome children misc neurological disorders secondary cerebrovascular involvement reported 10 cases 4 children ischemic stroke 3 intracerebral hemorrhage 1 cerebral sinus venous thrombosis 1 subarachnoid hemorrhage 1 multiple diffuse microhemorrhages reversible splenial lesions recognized 9 cases benign intracranial hypertension 4 patients meningoencephalitis 4 cases autoimmune encephalitis 1 girl cranial nerves impairment 2 patients transverse myelitis 1 case five cases guillainbarr syndrome gbs two including ours adem radiological investigations performed almost cases 45 60 recurrent radiological finding signal change splenium corpus callosum presence sarscov2 viral nucleic acid cerebrospinal fluid proved 2 cases outcome favorable almost except 5 casesconclusionsour research highlights large range neurological manifestations presumed pathogenic pathways associated sarscov2 infection children nervous system involvement isolated developing covid19 recovery arise context misc reported neurological manifestations cerebrovascular accidents reversible splenial lesions gbs benign intracranial hypertension meningoencephalitis adem also possible complication observed patient studies required investigate neurological complications sarscov2 infection underlying pathogenic mechanism,0.0
direct indirect costs costdriving factors adults tuberous sclerosis complex multicenter cohort study review literature background tuberous sclerosis complex tsc monogenetic multisystem disorder characterized benign growths due tsc1 tsc2 mutations german multicenter study estimated costs related cost drivers associated organ manifestations adults tscmethodsa validated threemonth retrospective questionnaire assessed sociodemographic clinical characteristics organ manifestations direct indirect outofpocket oop nursing carelevel costs among adult individuals tsc throughout germany societal perspective costing year 2019 resultswe enrolled 192 adults tsc mean age 334 127 years range 1878 years 516 n 99 women reported tsc disease manifestations included skin 948 kidney urinary tract 74 disorders epilepsy 729 structural brain defects 672 psychiatric disorders 505 heart circulatory system disorders 505 lymphangioleiomyomatosis 115 tsc1 tsc2 mutations reported 167 25 respondents respectively mean direct health care costs totaled eur 6452 median eur 1920 95 confidence interval ci eur 55337422 per patient three months medication costs represented major direct cost category 77 total direct costs mean eur 4953 mechanistic target rapamycin mtor inhibitors represented largest share 68 eur 4358 mean antiseizure drug asd costs eur 415 6 inpatient costs 8 eur 518 outpatient treatment costs 7 eur 467 important direct cost components mean care grade allowance approximator informal nursing care costs eur 929 median eur 0 95 ci eur 7801083 three months mean indirect costs totaled eur 3174 median eur 0 95 ci eur 25033840 among workingage individuals 67 years germany multiple regression analyses revealed mtor inhibitor use persistent seizures independent costdriving factors total direct costs older age disability independent costdriving factors total indirect costs whereas epilepsy psychiatric disease disability independent costdriving factors nursing care costsconclusionsthis threemonth study revealed substantial direct healthcare indirect healthcare medication costs associated tsc germany study highlights spectrum organ manifestations associated treatment needs german healthcare setting trial registration drks drks00016045 registered 01 march 2019 http wwwdrksde drks00016045,0.0
radiusoptimized efficient template matching lesion detection brain images sci rep 2021 jun 2 11 1 11586 doi 101038 s41598021901470abstractcomputeraided detection brain lesions volumetric magnetic resonance imaging mri demand fast automatic diagnosis neural diseases templatematching technique can provide satisfactory outcome automatic localization brain lesions however finding optimal template size maximizes similarity template lesion remains challenging increases complexity algorithm requirement computational resources processing large mri volumes threedimensional 3d templates hence reducing computational complexity template matching needed paper first propose mathematical framework computing normalized crosscorrelation coefficient nccc similarity measure mri volume approximated 3d gaussian template linear time complexity formula see text opposed conventional fast fourier transform fft based approach complexity formula see text formula see text number voxels image formula see text number tried template radii propose mathematical formulation analytically estimate optimal template radius voxel image compute nccc locationdependent optimal radius reducing complexity formula see text test methods one synthetic two real multiplesclerosis databases compare performances lesion detection fft stateoftheart lesion prediction algorithm demonstrate experiments efficiency proposed methods brain lesion detection comparable performance existing techniquespmid34078935 doi101038 s41598021901470,0.0
experiences communitydwelling older people dementia participating personcentred multidimensional interdisciplinary rehabilitation program background great need development feasible rehabilitation older people dementia increased understanding populations experiences rehabilitation participation therefore important aim study explore experiences communitydwelling older people dementia participating personcentred multidimensional interdisciplinary rehabilitation programmethodssixteen older people dementia interviewed experiences participation personcentred multidimensional interdisciplinary rehabilitation program program comprised assessments comprehensive team rehabilitation professionals followed rehabilitation period 16 weeks including interventions based individualized rehabilitation goals conducted support rehabilitation team rehabilitation performed participants homes community outpatient clinic including exercise social interaction small groups offered twice week participants interviews conducted end rehabilitation period analysed qualitative content analysisresultsthe analysis resulted one overarching theme empowered participation togetherness four subthemes strengthened challenges gaining insights motives raising concerns future seen makes participation worthwhile feelings togetherness prosperity adversity participants increased selfesteem daring coping rehabilitation insights condition motivated continue prioritized activities also raised concerns future play collaboration group seen acknowledged staff strengthened motivation selfefficacyconclusionaccording communitydwelling older people dementia personcentred multidimensional interdisciplinary rehabilitation program experienced viable beneficial participants seemed empowered rehabilitation expressed mostly positive experiences perceived improvements providers interdisciplinary rehabilitation programs group consider aspects raised participants eg positive experience challenged exercise daily activities importance seen feeling secure benefits challenges collaboration others situation generation new perspectives current future situation,0.0
selfmanagement selfesteem associations psychological wellbeing people multiple sclerosis abstractbackgroundoptimal selfmanagement seem protective factor healthrelated quality life psychological wellbeing many chronic conditions however results people multiple sclerosis ms still inconclusive thus aim study assess associations selfmanagement selfesteem psychological wellbeing people ms controlled sociodemographic clinical variablesmethodsa total 165 people ms filled multiple sclerosis selfmanagement scale rosenberg selfesteem scale general health questionnaire28 assess main variables study functional status measured kurtzke disability status scaleresultswe found significant associations selfesteem somatic symptoms anxiety insomnia social dysfunction severe depression explained variance models ranged 16 38 somatic symptoms severe depression respectively selfmanagement significantly contributed explained variance models sans ghq social dysfunction selfesteem significant contributor overall variance modelsdiscussionaccording results selfmanagement selfesteem found associated multiple domains psychological wellbeing findings may used neurological practice help people ms report psychological distress one domains,0.0
cognitivemotor interference individuals neurologic disorder systematic review neural correlates cogn behav neurol 2021 jun 2 34 2 7995 doi 101097 wnn0000000000000269abstractbackground performing cognitive task motor task simultaneously everyday act can lead decreased performance tasksobjective provide insight neural correlates associated cognitivemotor dual tasking individuals neurologic disordermethod searched pubmed web science databases studies published january 16th 2019 studies investigating neural correlates cognitivemotor dual task performance individuals variety neurologic disorders included independently whether study included healthy controls clinical imaging data abstracted comparison single tasks dual task individuals neurologic disorder comparison healthy controls individuals neurologic disorderresults eighteen studies met inclusion criteria study populations included individuals parkinson disease multiple sclerosis mild cognitive impairment alzheimer disease traumatic brain injury stroke neuroimaging types used study neural correlates cognitivemotor dual tasking upper limb gait tasks included fmri functional nearinfrared spectroscopy eeg petconclusion despite large heterogeneity study methodologies recurrent patterns noted particularly neurologic patients already higher brain activation single tasks seen compared healthy controls perhaps compromising patients ability adapt brain activation increasing load dual tasking resulting reduced behavioral dual task performancepmid34074863 doi101097 wnn0000000000000269,0.0
central peripheral nervous system involvement covid19 systematic review pathophysiology clinical manifestations neuropathology neuroimaging electrophysiology cerebrospinal fluid findings background sarscov2 can affect human brain neurological structures increasing number publications report neurological manifestations patients covid19 however studies comprehensively reviewed clinical paraclinical characteristics central peripheral nervous systems involvement patients study aimed describe features central peripheral nervous system involvement covid19 terms pathophysiology clinical manifestations neuropathology neuroimaging electrophysiology cerebrospinal fluid findingsmethodswe conducted comprehensive systematic review original studies reporting patients neurological involvement covid19 december 2019 june 2020 without language restriction excluded studies animal subjects studies related nervous system opinion articles data analysis combined descriptive measures frequency measures central tendency measures dispersion measures studies reporting neurological conditions abnormal ancillary tests patients confirmed covid19resultsa total 143 observational descriptive studies reported central peripheral nervous system involvement covid19 10 723 patients fiftyone studies described pathophysiologic mechanisms neurological involvement covid19 119 focused clinical manifestations 4 described neuropathology findings 62 described neuroimaging findings 28 electrophysiology findings 60 studies reported cerebrospinal fluid results reviewed studies reflect significant prevalence nervous systems involvement patients covid19 ranging 225 364 among different studies without mortality rates explicitly associated neurological involvement sarscov2 thoroughly describe clinical paraclinical characteristics neurological involvement patientsconclusionsour evidence synthesis led categorical analysis central peripheral neurological involvement covid19 provided comprehensive explanation reported pathophysiological mechanisms sarscov2 infection may cause neurological impairment international collaborative efforts exhaustive neurological registries will enhance translational knowledge covid19s central peripheral neurological involvement generate therapeutic decisionmaking strategiesregistrationthis review registered prospero 2020 crd42020193140 available https wwwcrdyorkacuk prospero display_recordphpidcrd42020193140,0.0
fear covid19 problems accessing medical appointments subjective experience disease progression predict anxiety depression reactions patients multiple sclerosis abstractbackgroundduring current covid19 pandemic studies suggested negative impact pandemic mental health patients multiple sclerosis pwms sense several factors may related increase experiences anxiety depression pwms current pandemicobjectivein study first explored reactions anxiety depression fear covid19 group pwms belong iberoamerican region besides explored whether positive covid19 fear covid19 obstacles attend medical appointments outbreak subjective experience ms progression predict anxiety depression reactions pwms samplematerials methodsan online crosssectional survey conducted 202 ms patients six countries argentina mexico spain dominican republic venezuela cuba comparisons variables independentsamples ttest oneway analysis variance used multiple linear regression used evaluate effects potential predictor variables emotional reactionsresultsour results showed pwms positive covid19 reported higher levels fear covid19 p001 also higher levels anxiety p001 compared nonpositive patients patients difficulties attending medical appointments outbreak showed higher levels depression p03 anxiety p019 levels anxiety p001 depression p006 also higher among patients subjective experience ms disease progression reactions fear covid19 positive covid19 problems attending medical appointments subjective experience ms disease progression showed high association negative impact pandemic mental health pwmsconclusionsour results show situation generated covid19 pandemic negative impact mental health pwms sample results also alert importance offering psychological care patients multiple sclerosis current outbreak regardless whether positive covid19,0.0
norce noncoding rna sets cis enrichment tool abstract background noncoding rnas ncrnas assigned critical regulatory roles remain functionally uncharacterized presents challenge whenever interesting set ncrnas needs analyzed functional context transcripts located closeby genome often regulated together genomic proximity sequence can hint functional association results present tool norce performs cis enrichment analysis given set ncrnas enrichment carried using functional annotations coding genes located proximal input ncrnas biologically relevant information topologically associating domain tad boundaries coexpression patterns mirna target prediction information can incorporated conduct richer enrichment analysis end norce includes several relevant datasets part data repository including cellline specific tad boundaries functional gene sets expression data coding ncrnas specific cancer additionally users can utilize custom data files investigation enrichment results can retrieved tabular format visualized several different ways norce currently available following species human mouse rat zebrafish fruit fly worm yeast conclusions norce platformindependent userfriendly comprehensive r package can used gain insight functional importance list ncrnas type tool offers flexibility conduct users preferred set analyses designing pipeline analysis norce available bioconductor https githubcom guldenolgun norce,0.0
vaccinations multiple sclerosis patients receiving diseasemodifying drugs curr opin neurol 2021 mar 11 doi 101097 wco0000000000000929 online ahead printabstractpurpose review review focuses new evidence supporting global immunization strategy multiple sclerosis ms patients receiving diseasemodifying drugs dmds including recently available vaccines severe acute respiratory syndrome coronavirus 2 sarscov2 infectionrecent findings new data strengthen evidence causal link ms vaccination recent consensus statements agree need start vaccination early timings vaccine administration adjusted ensure safety optimize vaccine responses given potential interference dmds patients treated ocrelizumab potentially bcell depleting therapies risk diminished immunogenicity vaccines relevant implications upcoming vaccination sarscov2summary early assessment immunization ms patients allows optimizing vaccine responses avoiding potential interference treatment plans vaccinations safe effective specific considerations followed vaccinating receiving immunotherapy timewindow vaccination taking account kinetics b cell repopulation potentially improve vaccine responses understanding sarscov2 vaccine response dynamics ms patients specific therapies will key defining best vaccination strategypmid33709979 doi101097 wco0000000000000929,0.0
functional correlates motor control impairments multiple sclerosis 7 tesla task functional mri study hum brain mapp 2021 mar 5 doi 101002 hbm25389 online ahead printabstractupper lower limb impairments common people multiple sclerosis pwms yet difficult clinically identify early stages disease progression tasks involving complex motor control can potentially reveal subtle deficits early stages can performed functional mri fmri acquisition investigate underlying neural mechanisms providing markers early motor progression investigated brain activation visually guided force matching hand foot 28 minimally disabled pwms expanded disability status scale edss 4 pyramidal cerebellar kurtzke functional systems scores 2 17 healthy controls hc using ultrahigh field 7tesla fmri allowing us visualise sensorimotor network activity high detail task activations performance tracking lag error compared groups correlations performed pwms showed delayed +124 s p 002 erroneous +015 n p 001 lower limb tracking together lower cerebellar occipital superior parietal cortical activation compared hc lower activity within regions correlated worse edss p 034 lower force error p 006 higher lesion load p 05 despite differences upper limb task performance pwms displayed lower inferior occipital cortical activation results demonstrate ultrahigh field fmri complex hand foot tracking can identify subtle impairments lower limb movements upper lower limb brain activity differentiates upper lower limb impairments minimally disabled pwmspmid33666314 doi101002 hbm25389,0.0
gut microbiome alphadiversity marker parkinson#39 s disease multiple sclerosis brain commun 2021 jun 1 3 2 fcab113 doi 101093 braincomms fcab113 ecollection 2021abstractthe gutbrain axis may play central role pathogenesis neurological disorders dozens casecontrol studies carried identify bacterial markers use targeted metagenomics alterations several taxonomic profiles confirmed across several populations however consensus made regarding alphadiversity recent publication described validated novel method based richness evenness measures gut microbiome order reduce complexity multiplicity alphadiversity indices used recently described richness evenness composite measures investigate potential link gut microbiome alphadiversity neurological disorders determine extent used marker diagnose neurological disorders stool samples performed exhaustive review literature identify original published clinical studies including 16s rrna gene sequencing parkinsons disease multiple sclerosis alzheimers disease richness evenness factors loadings quantified sequencing files addition shannon diversity index disease performed metaanalysis comparing indices patients healthy controls seven studies metaanalysed parkinsons disease corresponding 1067 subjects 631 parkinsons disease 436 healthy controls five studies metaanalysed multiple sclerosis corresponding 303 subjects 164 multiple sclerosis 139 healthy controls alzheimers disease metaanalysis done two studies matched criteria neither richness evenness significantly altered parkinsons disease multiple sclerosis patients comparison healthy controls pvalue 005 shannon index neither associated neurological disorders pvalue 005 adjusting age sex none alphadiversity measures associated parkinsons disease first report investigating systematically alphadiversity potential link neurological disorders study demonstrated unlike gastrointestinal immune metabolic disorders loss bacterial diversity associated parkinsons disease multiple sclerosispmid34704023 pmcpmc8195527 doi101093 braincomms fcab113,0.0
risk factors associated multiple sclerosis casecontrol study damascus syria mult scler int 2021 jun 1 20218147451 doi 101155 2021 8147451 ecollection 2021abstractobjectives assess probable risk factors associated multiple sclerosis among syrian patients city damascusmethod casecontrol study conducted may september 2020 140 ms patients 140 healthy controls selected two main hospitals damascus data regarding risk factors associated ms collected via structured questionnaire complementary laboratory tests statistical analysis carried spss statistical software version 26results factors smoking family history ms migraine vitamin d deficiency associated higher risk developing ms smoking 2275 95 ci 13483841 p 0002 family history ms 3970 95 ci 18078719 p 0001 migraine 3011 95 ci 13456741 p 0005 vitamin d deficiency 4778 95 ci 28637972 p 0001 however factors diabetes hypertension surgical history appendectomy tonsillectomy firstborn family statistically irrelevant diabetes 0652 95 ci 02261882 p 0426 hypertension 1445 95 ci 07242885 p 0295 appendectomy 1269 95 ci 04863317 p 0626 tonsillectomy 1280 95 ci 05762843 p 0544 firstborn child 0933 95 ci 05581562 p 0793 conclusion study suggests smoking vitamin d deficiency family history ms migraine probable risk factors multiple sclerosis therefore engaging outdoor activities maintaining healthy dietfor females particularis highly recommendedpmid34123428 pmcpmc8189778 doi101155 2021 8147451,0.0
positive predictive value myelin oligodendrocyte glycoprotein autoantibody testing jama neurol 2021 apr 26 doi 101001 jamaneurol20210912 online ahead printabstractimportance myelin oligodendrocyte glycoproteinigg1associated disorder mogad distinct central nervous systemdemyelinating disease positive results mogigg1 testing live cellbased assays can confirm mogad diagnosis falsepositive results may occurobjective determine positive predictive value ppv mogigg1 testing tertiary referral centerdesign setting participants diagnostic study conducted 2 years january 1 2018 december 31 2019 patients mayo clinic consecutively tested mogigg1 live cellbased flow cytometry diagnostic workup included patients without research authorization excludedmain outcomes measures medical records patients tested initially reviewed 2 investigators blinded mogigg1 serostatus pretest probability classified high low suggestive mogad testing mogigg1 used livecell fluorescenceactivated cellsorting assay igg binding index value 25 end titer 120 considered positive cases positive mogigg1 independently designated 2 neurologists truepositive falsepositive results last followup based current international recommendations diagnosis identification alternative diagnoses consensus reached cases disagreement existedresults total 1617 patients tested 357 excluded among 1260 included patients tested 2 years median range age testing 46 098 years 792 patients female 629 total 92 1260 73 positive mogigg1 twentysix results 28 designated false positive 2 raters overall agreement 91 92 cases 99 true false positivity alternative diagnoses included multiple sclerosis n 11 infarction n 3 b12 deficiency n 2 neoplasia n 2 genetically confirmed adrenomyeloneuropathy n 1 conditions n 7 overall ppv number truepositive results total positive results 72 95 ci 6280 titer dependent ppvs 11000 100 1100 82 12040 51 median titer higher truepositive results 1100 range 120110000 falsepositive results 140 range 1201100 p 001 ppv higher children 94 95 ci 7299 vs adults 67 95 ci 5677 patients high pretest probability 85 95 ci 7692 vs low pretest probability 12 95 ci 334 specificity mogigg1 testing 978conclusions relevance study confirms mogigg1 highly specific biomarker mogad using cutoff 120 low ppv 72 caution advised interpretation low titers among patients atypical phenotypes ordering mogigg1 low pretest probability situations will increase proportion falsepositive resultspmid33900394 doi101001 jamaneurol20210912,1.0
editorial challenges diagnosis treatment multiple sclerosis curr opin neurol 2021 jun 1 34 3 275276 doi 101097 wco0000000000000940no abstractpmid33935216 doi101097 wco0000000000000940,0.0
propionic acid rescues highfat diet enhanced immunopathology autoimmunity via effects th17 responses front immunol 2021 jun 1 12701626 doi 103389 fimmu2021701626 ecollection 2021abstracthighfat diets hfd linked obesity associated comorbidities induce pathogenic t helper th 17 cells decreasing regulatory t cells treg proinflammatory environment also aggravates immunopathology experimental autoimmune encephalomyelitis eae prototype model t cell mediated autoimmunity strong association hfd obesity well increasing risk autoimmunity western world stresses importance identify compounds counteract metabolically induced proinflammatory state humans one prominent candidate shortchain fatty acid propionate pa recently identified potent therapy autoimmune disease multiple sclerosis enhancing treg cell frequencies functionality mice fed hfd rich lauric acid la treated either water pa mog3555eae analyzed treg th17 cell frequencies different tissues antigenspecific cell proliferation cytokine secretion investigated treg cell functionality suppression assays il10 signaling blockade employed western blotting investigate involvement p38mapk signaling finally performed explorative study obese nonobese ms patients investigating fecal pa concentrations well peripheral th17 treg frequencies 90 days daily pa intake compared controls mice hfd displayed severe course eae enhanced demyelination immune cell infiltration spinal cord pa treatment prevented disease enhancing effect hfd inhibiting th17 mediated inflammatory processes gut spleen blocking experiments signaling studies revealed p38mapk il10 signaling important targets linking beneficial effects pa treatment reduced inflammation due enhanced treg frequency functionality explorative study small group ms patients revealed reduced pa concentrations fecal samples obese ms patients compared nonobese group coinciding increased th17 decreased treg cells obese patients importantly pa intake restore tregth17 homeostasis data thus identify th17 responses important target beneficial effects pa hfd obesity addition recently identified potential pa treg inducing therapy t cell mediated autoimmunitypmid34140958 pmcpmc8204048 doi103389 fimmu2021701626,1.0
comparison structure function retina optic nerve patients history multiple sclerosisrelated demyelinating retrobulbar optic neuritis treated treated systemic steroid therapy clin ophthalmol 2021 jun 1 1522532261 doi 102147 opths309975 ecollection 2021abstractpurpose compare structure function retina optic nerve patients history multiple sclerosis ms related demyelinating retrobulbar optic neuritis treated treated systemic steroid therapypatients methods thirtytwo eyes 32 ms patients past single episode msrelated demyelinating retrobulbar divided 2 groups s + consisting 16 patients treated intravenous methylprednisolone dose 1g day 3 days acute stage s consisting 16 patients receive treatment following examinations performed distance bestcorrected visual acuity dbcva snellen slitlamp examination anterior posterior segment eye 90d volk lens visual field analysis carl zeiss humphrey 750 visual field analyzer 242 ww macular thickness foveal rt1 parafoveal region rt2 well peripapillary retinal nerve fiber layer thickness rnfl temporal superior nasal inferior quadrants carl zeiss cirrus hdoct assessment bioelectrical function visual pathway emphasis optic nerve pattern visual evoked potentials pvep macular ganglion cells cone photoreceptors pattern electroretinogram perg roland consult results statistically significant differences observed investigated groups terms dbcva mean deviation visual field macular rt1 rt2 rnfl thickness temporal superior nasal inferior quadrants well bioelectrical function pvep perg conclusion application steroid therapy considered individual basis routine treatment patientpmid34103889 pmcpmc8180287 doi102147 opths309975,1.0
bcg turns 100 nontraditional uses viruses cancer immunologic diseases j clin invest 2021 jun 1 131 11 148291 doi 101172 jci148291abstractfirst administered human subject tuberculosis tb vaccine july 18 1921 bacillus calmettegurin bcg long history use prevention tb later immunotherapy bladder cancer tb prevention bcg given infants born globally across 180 countries use since late 1920s 352 million bcg doses procured annually tens billions doses administered past century estimated widely used vaccine human history roles tb prevention bladder cancer immunotherapy widely appreciated past century bcg also studied nontraditional purposes include prevention viral infections nontuberculous mycobacterial infections b cancer immunotherapy aside bladder cancer c immunologic diseases including multiple sclerosis type 1 diabetes atopic diseases basis heterologous effects lies ability bcg alter immunologic set points via heterologous t cell immunity well epigenetic metabolomic changes innate immune cells process called trained immunity review provide overview known regarding trained immunity mechanism heterologous protection describe current knowledge base nontraditional uses bcgpmid34060492 doi101172 jci148291,0.0
clinical utility antiretinal antibody testing jama ophthalmol 2021 apr 22 doi 101001 jamaophthalmol20210651 online ahead printabstractimportance clinical utility antiretinal antibodies retina antibodies currently available testing remains unclear unproven despite presence retinal antibodies included current diagnostic autoimmune retinopathy criteriaobjective evaluate clinical significance comprehensive retinal antibody evaluations currently offered north americadesign setting participants crosssectional study 14 patients without autoimmune retinopathy recruited mayo clinic neuroimmunology biorepository study january 1 2019 october 1 2019 serum samples without autoimmune retinopathy sent masked fashion clinical laboratory improvement amendmentscertified laboratory using similar methods mayo clinic neuroimmunology research laboratory independently assessed sample ascertain reproducibility findingsmain outcomes measures results autoimmune retinopathy cancerassociated retinopathy panelsresults thirteen 14 93 95 ci 66100 serum samples tested positive retinal antibodies median 5 retinal antibodies range 08 per patient clinical laboratory improvement amendmentscertified laboratory provides specificity 7 95 ci 034 confirmatory immunohistochemistry staining human retina present 12 14 samples 86 enolase found 9 64 retinal antibody present recoverin nonspecific retinal antibody results replicated mayo clinic laboratory western blot using pig retina proteins substrateconclusions relevance presence retinal antibodies 93 patients without autoimmune retinopathy indicates lack specificity detectable retinal antibodies limited clinical relevance evaluation patients suspected autoimmune retinopathy current retinal antibody testing recoverin interpreted caution especially cases low clinical suspicion poor specificity important recognize prevent potentially unnecessary commencement systemic immunosuppressants may result significant extraocular adverse effects identification biomarkers high predictive value inflammatory autoimmune retinal diseases needed move field forwardpmid33885761 doi101001 jamaophthalmol20210651,0.0
early multiple sclerosis diagnostic challenges clinically radiologically isolated syndrome patients curr opin neurol 2021 mar 1 doi 101097 wco0000000000000921 online ahead printabstractpurpose review introduction new diagnostic criteria sensibility multiple sclerosis ms diagnosis increased number cases clinically isolated syndrome cis decreased nevertheless misdiagnosis might always around corner exclusion better explanation mandatorythere pressing need provide update main prognostic factors increase risk conversion cis radiologically isolated syndrome ris ms potential red flags consider diagnostic workuprecent findings discuss diagnostic challenges facing patients presenting first demyelinating attack ris focus recently revised diagnostic criteria neuroinflammatory conditions considered differential diagnosis factors distinguishing patients risk developing msa correct definition typical demyelinating attack well correct interpretation mri findings remains crucial diagnostic process cerebrospinal fluid examination warmly recommended confirm dissemination time demyelinating process increase diagnostic accuracysummary early accurate diagnosis ms requires careful consideration clinical paraclinical radiological data well reliable exclusion mimicking pathological conditions advocated promptly initiate appropriate diseasemodifying therapy can impact positively longterm outcome diseasepmid33661162 doi101097 wco0000000000000921,1.0
progressive multifocal leukoencephalopathy patient progressive multiple sclerosis treated ocrelizumab monotherapy jama neurol 2021 mar 16 doi 101001 jamaneurol20210627 online ahead printabstractimportance progressive multifocal leukoencephalopathy pml opportunistic infection caused jc virus proven effective treatment although rare cases pml occurred anticd20 therapies prior cases associated ocrelizumabobjective report first ever case pml occurring ocrelizumab monotherapy patient progressive multiple sclerosis without prior immunomodulationdesign setting participant case reported academic medical center patient multiple sclerosis receiving ocrelizumab monotherapyexposures ocrelizumab monotherapyresults 78yearold man progressive multiple sclerosis treated ocrelizumab monotherapy 2 years presented 2 weeks progressive visual disturbance confusion examination demonstrated right homonymous hemianopia magnetic resonance imaging revealed enlarging nonenhancing left parietal lesion without mass effect cerebrospinal fluid revealed 1000 copies ml jc virus confirming diagnosis pml blood work diagnosis revealed grade 2 lymphopenia absolute lymphocyte count 710 l cd4 294 l reference range 3251251 l cd8 85 l reference range 90775 l cd19 1 l preserved cd4 cd8 ratio 345 negative hiv serology retrospective absolute lymphocyte count revealed intermittent grade 1 lymphopenia preceded ocrelizumab absolute lymphocyte count range 8001200 l patients symptoms progressed weeks involve bilateral visual loss rightsided facial droop dysphasia ocrelizumab discontinued offlabel pembrolizumab treatment initiated patient nevertheless declined rapidly ultimately died pml confirmed autopsyconclusions relevance case report pml occurrence likely result immunomodulatory function ocrelizumab well agerelated immunosenescence case report emphasizes importance thorough discussion risks benefits ocrelizumab especially patients higher risk infections elderly patientspmid33724354 doi101001 jamaneurol20210627,0.0
citrullination pad enzyme biology type 1 diabetes regulators inflammation autoimmunity pathology front immunol 2021 jun 1 12678953 doi 103389 fimmu2021678953 ecollection 2021abstractthe generation posttranslational modifications ptms human proteins physiological process leading structural immunologic variety proteins potentially altered biological functions ptms often arise normal responses cellular stress including general oxidative changes tissue microenvironment intracellular stress endoplasmic reticulum immunemediated inflammatory stresses many studies now illustrated presence neoepitopes consisting ptm selfproteins induce robust autoimmune responses pathways inflammatory neoepitope generation commonly observed many autoimmune diseases including systemic lupus erythematosus rheumatoid arthritis multiple sclerosis type 1 diabetes t1d among others review will focus one specific ptm selfproteins known citrullination citrullination mediated calciumdependent peptidylarginine deiminase pad enzymes catalyze deimination conversion arginine nonclassical amino acid citrulline pads citrullinated peptides associated different autoimmune diseases notably prominent role diagnosis pathology rheumatoid arthritis recently important role pads citrullinated selfproteins emerged t1d review will provide comprehensive overview pathogenic role pads citrullination inflammation autoimmunity specific focus evidence role t1d general role pads epigenetic transcriptional processes well crucial role histone citrullination neutrophil biology neutrophil extracellular trap net formation will discussed latter important view increasing evidence role neutrophils netosis pathogenesis t1d will discuss underlying processes leading citrullination genetic susceptibility factors increased recognition citrullinated epitopes t1d hlasusceptibility types provide overview reported autoreactive responses citrullinated epitopes t cells autoantibodies t1d patients finally will discuss recent observations obtained nod mice pointing prevention diabetes development pad inhibition potential role pad inhibitors novel therapeutic strategy autoimmunity t1d particularpmid34140951 pmcpmc8204103 doi103389 fimmu2021678953,0.0
13th postectrims meeting review new developments presented 2020 ectrims congress rev neurol 2021 jun 1 72 11 397406 doi 1033588 rn72112021172abstractintroduction decade following ectrims congress postectrims meeting held spain neurologists expertise multiple sclerosis ms country meet review relevant latest developments presented ectrims congress occasion held together actrims aim article published two parts summarises presentations took place postectrims meeting held online 16 17 october 2020development first part includes latest results regarding impact environment lifestyle risk ms clinical course role epigenetics genetic factors processes findings preclinical clinical research lymphocyte subtypes identified involvement lymphoid follicles meningeal involvement disease discussed changes brain structure addressed microscopic macroscopic levels including results highresolution imaging techniques latest advances biomarkers diagnosis prognosis ms involvement microbiome patients also reported finally results patient registries impact covid19 ms patients outlinedconclusions new data ms risk factors impact ms cellular structural level role microbiome disease biomarkers relationship covid19 mspmid34042168 doi1033588 rn72112021172,0.0
shortterm exercise program patients multiple sclerosis body mass index important int j rehabil res 2021 mar 12 doi 101097 mrr0000000000000462 online ahead printabstractobesity health problem can exacerbate symptoms multiple sclerosis ms current study aimed investigate effectiveness shortterm exercise program fatigue depression anxiety walking performance normalweight overweight patients ms pwms sixtytwo pwms divided groups according bmi bmi normal bmi high also included exercise program participants took moderateintensity walking program 5 days week 4 weeks including 30 min 5 min warmup 5 min cooling periods also patients underwent breathing posture flexibility stretching exercises 4 weeks fatigue depression anxiety 6minute walking test 6mwt bmi measured 4 weeks exercise program statistically significant improvements fatigue depression anxiety 6mwt however relation detected examined variables bmi patients participated effectively exercise program regardless bmi results obtained study support shortterm exercise program effective therapeutic intervention unrelated bmi improving fatigue depression anxiety walking performance pwmspmid33724971 doi101097 mrr0000000000000462,0.0
highly effective diseasemodifying treatment initial ms therapy curr opin neurol 2021 mar 31 doi 101097 wco0000000000000937 online ahead printabstractpurpose review using highly effective compounds right beginning diseasemodifying immunotherapy dmt people multiple sclerosis pwms gained popularity among clinicians pwms alike discuss recent evidence supporting approach whether associated risks stop us adopting default strategyrecent findings addition injectable ofatumumab two oral sphingosines one phosphate modulators siponimod ozanimod ten dmts now available pwms though variation licensing status cost may limit use healthcare environments real world evidence based large ms registry data suggests superiority early dmt slow treatment escalation approach delaying dmt leads rapid often irreversible disability accrual mechanistically bcell depletion particularly memory bcell suppression common denominator closely associated dmt efficacysummary concept dmts necessarily associated high risk adverse effects longer supported evidence rather predictable manageable risk profile dmts lower threshold clinicians discuss treatment pwms first line approachpmid33840776 doi101097 wco0000000000000937,0.0
predicting disability worsening relapsing progressive multiple sclerosis curr opin neurol 2021 mar 11 doi 101097 wco0000000000000928 online ahead printabstractpurpose review multiple sclerosis ms clinically heterogeneous disease complicates expectant management well treatment decisions review provides overview well established emerging predictors disability worsening including clinical factors imaging factors biomarkers treatment strategiesrecent findings addition well known clinical predictors age male sex clinical presentation relapse behaviour smoking obesity vascular psychiatric comorbidities associated subsequent disability worsening persons ms number imaging features predictive disability worsening present varying degrees relapsing progressive forms ms include brain volumes spinal cord atrophy lesion volumes optical coherence tomography features cerebrospinal recently blood biomarkers including neurofilament light show promise easily attainable biomarkers future disability accumulation importantly recent observational studies suggest initiation earlyintensive therapy opposed escalation based breakthrough disease associated decreased accumulation disability overall although randomized controlled trials investigating question underwaysummary understanding risk factors associated disability progression can help counsel patients enhance clinicians availability provide evidencebased treatment recommendationspmid33709974 doi101097 wco0000000000000928,0.0
ocrelizumab natalizumab jcvirus positive relapsing remitting multiple sclerosis patients mult scler j exp transl clin 2021 jun 1 7 2 20552173211013831 doi 101177 20552173211013831 ecollection 2021 aprjunabstractocrelizumab often used alternative therapy natalizumabtreated ms patients risk progressive multifocal leukoencephalopathy pml objective assess efficacy safety jcvirus positive patients switching either directly indirectly natalizumab ocrelizumab fortytwo patients included observational cohort median followup 21 months evidence disease activity found 83 direct switchers 50 indirect switchers two direct switchers diagnosed carryover pml data support direct switch adequate disease suppression although carryover pml illustrates dilemma choosing direct indirect switchpmid34123391 pmcpmc8175839 doi101177 20552173211013831,1.0
proresolving lipid mediator lipoxin a4 attenuates neuroinflammation modulating tnbsp cell responses modifies spinal cord lipidome cell rep 2021 jun 1 35 9 109201 doi 101016 jcelrep2021109201abstractthe chronic neuroinflammatory character multiple sclerosis ms suggests natural process resolve inflammation impaired protective process orchestrated specialized proresolving lipid mediators spms date role spms ms remains largely unknown provide vivo evidence treatment spm lipoxin a4 lxa4 ameliorates clinical symptoms experimental autoimmune encephalomyelitis eae inhibits cd4+ cd8+ t cell infiltration central nervous system cns moreover show lxa4 potently reduces encephalitogenic th1 th17 effector functions vivo isolated human t cells healthy donors patients relapsingremitting ms finally demonstrate lxa4 affects spinal cord lipidome significantly reducing levels proinflammatory lipid mediators eae collectively findings provide mechanistic insight lxa4mediated amelioration neuroinflammation highlight potential clinical application lxa4 mspmid34077725 doi101016 jcelrep2021109201,1.0
cannabinoid system microglia health disease neuropharmacology 2021 apr 9108555 doi 101016 jneuropharm2021108555 online ahead printabstractrecent years yielded significant advances understanding microglia immune cells central nervous system cns microglia key players cns development immune surveillance maintenance proper neuronal function throughout life healthy brain homeostatic microglia unique molecular signature neurological diseases microglia become activated adopt distinct transcriptomic signatures including diseaseassociated microglia dam implicated neurodegenerative disorders homeostatic microglia synthesise endogenous cannabinoids 2arachidonoylglycerol anandamide express cannabinoid receptors cb1 cb2 constitutively low levels upon activation microglia significantly increase synthesis endocannabinoids upregulate expression cb2 receptors promote protective microglial phenotype enhancing production neuroprotective factors reducing production proinflammatory factors summarise effects microglial cannabinoid system cns demyelinating disease multiple sclerosis neurodegenerative diseases alzheimers disease parkinsons disease amyotrophic lateral sclerosis chronic inflammatory neuropathic pain psychiatric disorders including depression anxiety schizophrenia discuss therapeutic potential cannabinoids regulating microglial activity highlight need investigate specific microgliadependent immunomodulatory effectspmid33845074 doi101016 jneuropharm2021108555,1.0
tuberous sclerosis skinmed 2021 jun 1 19 3 179185 ecollection 2021abstracttuberous sclerosis rare autosomal dominant genetic disorder characterized appearance benign tumors known hamartomas can affect multiple organs including skin cutaneous manifestations present almost patients therefore dermatologist fundamental role history evolution disease spite multisystemic disorder two tumor suppressor genes cet1 cet2 involved tissue growth cell proliferation show mutation disease leads appearance various benign tumors hamartomas clinical characteristics three hypomelanotic macules three angiofibromas face scalp cephalic fibrotic plaque two ungual fibromas shagreen plaque multiple retinal hamartomas etc treatment basically symptomatic genetic counseling important autosomal dominant disorder although spontaneous mutation familial history 65 patients one parents affected genetic study useful prenatal diagnosispmid34303387,0.0
meaning fabric orthoses longterm users multiple sclerosis interpretative phenomenological analysis prosthet orthot int 2021 mar 23 doi 101097 pxr0000000000000006 online ahead printabstractbackground fabric orthoses elasticated garments designed provide support musculoskeletal system may benefit people multiple sclerosis however population acceptability largely unexploredobjectives study aimed explore meaning fabric orthoses hold people multiple sclerosis factors influencing acceptabilitystudy design qualitative study using interpretative phenomenological analysis explore meaning ascribed lived experiencemethods four people multiple sclerosis participated facetoface semistructured interviews two used upper limb orthotic sleeves involuntary movement control one used orthotic shorts one used soft ankle brace three participants fabric orthoses longer used themes validated peer reviewfindings two themes identified giving back control describes perceived physical benefits decreased involuntary movement improved stability led important benefits autonomy selfimage orthoses worn longerterm selfimage improved learning live orthosis captures way participants learnt experience months years maximize effectiveness overcome disadvantages acceptability determined specific contexts orthoses used social appropriateness appearance demands tasks important considerationsconclusions fabric orthoses can acceptable people multiple sclerosis professionals mindful active learning process users engage learn pros cons orthotic use research effectiveness neededpmid33856158 doi101097 pxr0000000000000006,0.0
physical activity together people multiple sclerosis care partners protocol feasibility randomized controlled trial dyadic intervention jmir res protoc 2021 jun 1 10 6 e18410 doi 102196 18410abstractbackground physical activity pa beneficial people however people affected multiple sclerosis ms find regular pa challenging people may include individuals advanced disabilities care partnersobjective objective study determine feasibility dyadic pa intervention people advanced ms care partnersmethods study randomized controlled feasibility trial 12week intervention 11 allocation immediate intervention condition delayed control condition target 20 people mscare partner dyads will included outcomes will indicators process resources management scientific feasibility participant satisfaction intervention components will evaluated using satisfaction survey subjective experience participation study will explored using semistructured interviewsresults project funded consortium multiple sclerosis centers protocol approved ottawa hospital research ethics board 2019032901h university ottawa research ethics board h09194886 study protocol registered clinicaltrialsgov february 2020 findings feasibility trial will disseminated presentations community events engage ms population interpretation results next steps results will also published peerreviewed journals presented scientific community national international ms conferencesconclusions data collected feasibility trial will used refine intervention materials preparation pilot randomized controlled trialtrial registration clinicaltrialsgov nct04267185 https clinicaltrialsgov ct2 show nct04267185international registered report identifier irrid prr1102196 18410pmid34061040 doi102196 18410,0.0
serum tnf levels 24 h certolizumab pegol predict effectiveness week 12 patients rheumatoid arthritis tsubame study abstractobjectiveto estimate relationship serum tnf il6 serum czp levels clinical response czp ra patients tsubame studymethodsone hundred patients ra received czp enrolled multiple clinical parameters serum tnf il6 czp levels assessed 0 24 48 h 12 weeks first administration czpresultsthe czp therapy significantly improved das28 esr 12 weeks serum tnf il6 levels significantly decreased baseline 24 h first administration czp serum tnf levels baseline related clinical parameters baseline improvement das28 esr week 12 czp therapy however serum levels czp 24 h strongly negatively correlated tnf levels 24 h negatively correlated improved rate das28 esr week 12 serum levels tnf il6 24 h negative correlation achievement das28 esr 26 week 12 multivariate analysis odds ratio 001 95 confidence interval 004e2022 p 001 receiver operating characteristic analysis conducted estimate achievement das28 esr 26 week 12 czp therapy cutoff value 076 pg ml serum levels tnf 24 h yielded area curve075 das28 esr 26 achieved week 12 significantly patients lower serum tnf levels 076 pg ml 24 h higher tnf levelsconclusionsczp highly effective ra patients low serum tnf levels 24 h initial administration czp therefore propose serum tnf levels 24 h serve biomarker predicting effectiveness czp week 12 patients ratrial registrationclinical trial registration number umin id000022831,0.0
chinese patient developmental epileptic encephalopathies dee carrying trpm3 gene mutation paediatric case report background developmental epileptic encephalopathies dees heterogeneous group chronic encephalopathies characterized epilepsy comorbid intellectual disability frequently associated de novo nonsynonymous coding variants ion channels cellsurface receptors neuronally expressed genes mutations trpm3 identified cause dee report novel patient dee carrying de novo missense mutation trpm3 p s1202t missense mutation never reportedcase presentationa 7year 2monthold chinese patient recurrent polymorphic seizures clinically diagnosed dee de novo missense mutation trpm3 yet reported identified case patient clinical phenotype consistent previous reportsconclusionsthese findings expand spectrum trpm3 mutations might also support de novo substitutions trpm3 cause dee,0.0
use diseasemodifying drugs pregnancy breastfeeding curr opin neurol 2021 mar 11 doi 101097 wco0000000000000922 online ahead printabstractpurpose review fact multiple sclerosis ms predominantly affects women recognized many years age diagnosis decreasing treatment options becoming complex increasing numbers women facing decisions use disease modifying therapy dmt around pregnancyrecent findings new data rapidly becoming available particularly regarding safety therapies pregnancy breastfeeding effective treatment suppression relapses key ensuring good outcomes longer term woman however must balanced individual risk relapse risks fetus women advised possible breastfeed taking selected dmtsummary review discuss evidence surrounding safety dmts pregnancy breastfeeding use knowledge suggest approaches pregnancy family planning women mspmid33709977 doi101097 wco0000000000000922,0.0
update targeted therapies systemic sclerosis based systematic review last 3years abstractnew molecular mechanisms can targeted specific drugs recently emerged treatment systemic sclerosis ssc patients past 3 years achievement one large phase 3 trial led approval drug agencies first drug licenced sscrelated interstitial lung disease given exciting time ssc field aimed perform systemic literature review phase 1 phase 2 phase 3 clinical trials large observational studies targeted therapies ssc searched medline pubmed embase clinicaltrialsgov clinical studies 2016 targeted therapies primary treatment patients ssc skin lung involvement primary clinical outcome measure details study characteristics trial drug used molecular target engaged trial drug inclusion criteria study treatment dose possibility concomitant immunosuppression endpoints study duration study results obtained reviewed 973 references identified 21 4 conference abstracts 17 articles included systematic review total 15 phase 1 phase 2 clinical trials 2 phase 3 clinical trials 2 observation studies analysed drugs studied phase 1 phase 2 studies included following inebilizumab dabigatran c82 pomalidomide rilonacept romilkimab tocilizumab tofacitinib pirfenidone lenabasum abatacept belimumab riociguat sar100842 lanifibranor 3 studies performed early diffuse ssc patients different inclusion criteria 3 studies performed ssc patients interstitial lung disease ild phase 3 clinical trials investigated nintedanib tocilizumab nintedanib investigated sscild patients whereas tocilizumab focused early diffuse ssc patients inflammatory features two observational studies including 50 patients rituximab targeted drug also evaluated studies offer real hope ssc patients future challenges will customize patientspecific therapeutics goal develop precision medicine ssc,0.0
outcomes risk factors associated sarscov2 infection north american registry patients multiple sclerosis jama neurol 2021 mar 19 doi 101001 jamaneurol20210688 online ahead printabstractimportance emergence sarscov2 causing covid19 prompted need gather information clinical outcomes risk factors associated morbidity mortality patients multiple sclerosis ms concomitant sarscov2 infectionsobjective examine outcomes risk factors associated covid19 clinical severity large diverse cohort north american patients msdesign setting participants analysis used deidentified crosssectional data patients ms sarscov2 infection reported health care professionals north american academic community practices april 1 2020 december 12 2020 covid19 infections ms registry health care professionals asked report patients minimum 7 days initial symptom onset sufficient time passed observe covid19 disease course resolution acute illness death data collection began april 1 2020 ongoingexposures laboratorypositive sarscov2 infection highly suspected covid19main outcomes measures clinical outcome 4 levels increasing severity hospitalized hospitalization admission intensive care unit required ventilator support deathresults 1626 patients laboratorypositive sarscov2 infection 1345 827 female 1202 740 relapsingremitting ms 1255 804 total 996 patients 615 nonhispanic white 337 208 black 190 117 hispanic latinx mean sd age 477 132 years 797 495 1 comorbidity overall mortality rate 33 95 ci 2543 ambulatory disability older age independently associated increased odds clinical severity levels compared hospitalized adjusting risk factors nonambulatory hospitalization odds ratio 28 95 ci 1648 intensive care unit required ventilator support 35 95 ci 1678 death 254 95 ci 93691 age every 10 years hospitalization 13 95 ci 1116 intensive care unit required ventilator support 13 95 ci 09917 death 18 95 ci 1226 conclusions relevance registrybased crosssectional study increased disability independently associated worse clinical severity including death covid19 risk factors worse outcomes included older age black race cardiovascular comorbidities recent treatment corticosteroids knowledge risk factors may improve treatment patients ms covid19 helping clinicians identify patients requiring intense monitoring covid19 treatmentpmid33739362 doi101001 jamaneurol20210688,0.0
risk persistent disability patients pediatriconset multiple sclerosis jama neurol 2021 may 3 doi 101001 jamaneurol20211008 online ahead printabstractimportance availability new diseasemodifying therapies dmts changes therapeutic paradigms led general improvement multiple sclerosis ms prognosis adults still unclear whether improvement also involves patients pediatriconset ms poms whose early management challengingobjective evaluate changes prognosis poms time association changes therapeutic managing standardsdesign setting participants retrospective multicenter observational study data extracted collected may 2019 italian ms registry digital database including 59 000 patients inclusion criteria ms onset age 18 years diagnosis january 2014 disease duration least 3 years exclusion criteria primary progressive ms expanded disability status scale edss score least 8 one year onset unavailability diagnosis date less 2 edss score evaluations eligible patients 4704 patients poms according criteria enrolled 3198 patients excluding 1506exposures compared time reach disability milestones epoch ms diagnosis 1993 19931999 20002006 20072013 adjusting possible confounders linked edss evaluations clinical disease activity analyzed difference among 4 diagnosis epochs regarding demographic characteristics clinical disease activity onset dmts managementmain outcomes measures disability milestones edss score 40 60 confirmed following clinical evaluation last available visitresults enrolled 3198 patients poms mean age onset 152 years 69 female median time diagnosis 32 years annualized relapse rate first 1 3 years 13 06 respectively mean sd followup 218 117 years median survival times reach edss score 40 60 317 405 years cumulative risk reaching disability milestones gradually decreased time edss score 40 hazard ratio hr 070 95 ci 058083 19931999 hr 048 95 ci 038060 20002006 hr 044 95 ci 032059 20072013 60 hr 072 95 ci 057090 hr 044 95 ci 033060 hr 030 020046 later diagnosis epochs greater number patients poms treated dmts especially highpotency drugs given earlier longer period demographic characteristics clinical disease activity onset change significantly timeconclusions relevance poms risk persistent disability reduced 50 70 recent diagnosis epochs probably owing improvement therapeutic managing standardspmid33938921 doi101001 jamaneurol20211008,0.0
physicians#39 opinions necessity covid19 vaccination patients epilepsy epileptic disord 2021 may 31 doi 101684 epd20211282 online ahead printabstractthe aim current study investigate opinions neurologists psychiatrists iran necessity covid19 vaccination patients epilepsy pwe data can help policy makers understand concerns healthcare professionals survey study september 1st 2020 sent questionnaire using googleforms neurologists psychiatrists iran via whatsapp survey included three general questions age sex discipline six covidspecific questions total 202 physicians participated study 116 neurologists 86 psychiatrists participants 27 believed pwe increased risk contracting covid19 majority 74 participants confidently recommend covid19 vaccine patients however 49 physicians recommend vaccine patients others consider special populations overwhelming majority 91 participants recommend covid19 vaccine reliable vaccine becomes available many physicians trust vaccine approved world health organization 46 vaccine approved food drug administration fdausa 34 physicians concerns issue necessity future covid19 vaccine pwe important concern reliability vaccine regard two health agencies fda trusted organizations approve vaccine covid19pmid34057409 doi101684 epd20211282,0.0
rare case spinal cord injury following thoracic radiofrequency ablation cureus 2021 jun 1 13 6 e15380 doi 107759 cureus15380 ecollection 2021 junabstractmedial branch radiofrequency ablation rfa become common treatment facetrelated back pain procedure often performed lumbar cervical spinal segments can also applied thoracic spine complications spinal rfa level scarce literature often mild patient 37yearold male family history multiple sclerosis siblings underwent thoracic rfa t2t5 nerve root levels within one week procedure patient experienced paresthesias nipple line progressive lowerextremity weakness also found exhibit urinary retention presentation facility one month later mri showed focal cord short t1 inversion recovery stir signal abnormality t3t4 level favored represent myelomalacia extensive laboratory imaging workup otherwise unrevealing patient treated neuromodulators short course inpatient rehabilitation one year later used kneeanklefoot orthoses ambulating short distances manual wheelchair longer distances longer required intermittent catheterization bladder management case presents rare unusual timeline symptom evolution laboratory findings imaging results unveil clear pathophysiological mechanism led patients spinal cord injury clinical level injury based patients symptoms location myelomalacia mri however strongly support causative contribution thoracic rfa procedurepmid34249533 pmcpmc8253455 doi107759 cureus15380,0.0
amit baror breaking new ground multiple sclerosis among many fascinating scientific questions remain explored im particularly motivated whose answers will impact human health begins amit baror distinguished professor neurology clinician scientist baror university pennsylvania pa usa always thinking ahead unmet needs working harder contribution understanding immune cells subtypes interactions specifically bcell contributions multiple sclerosis broke new ground continues appearing remarkably grounded yes probably fair say agrees,0.0
classification multiple sclerosis based patterns cns regional atrophy covariance hum brain mapp 2021 feb 24 doi 101002 hbm25375 online ahead printabstractthere evidence multiple sclerosis ms pathology leads distinct patterns volume loss time vlot different central nervous system cns structures aimed use patterns identify patient subgroups ms patients classical disease phenotypes underwent annual clinical blood mri examinations 6 years spinal striatal pallidal thalamic cortical white matter t2weighted lesion volumes well serum neurofilament light chain snfl quantified cns vlot patterns identified using principal component analysis patients classified using hierarchical cluster analysis 225 ms patients classified four distinct groups b c d including 14 59 141 11 patients respectively groups differ baseline demographics disease duration disease phenotype distribution lesionload expansion interestingly group showed pronounced spinothalamic vlot group b marked pallidal vlot group c small betweenstructure vlot differences group d myelocortical volume increase pronounced white matter vlot neurologic deficits severe progressed faster group also higher mean snfl levels groups group b experienced frequent relapses group c conclusion distinct patterns vlot across cns ms patients overlap clinical ms subtypes independent disease duration lesionload partially associated snfl levels relapse rates clinical worsening findings support need biologic classification ms subtypes including volumetric bodyfluid markerspmid33624390 doi101002 hbm25375,0.0
targeting b cells multiple sclerosis curr opin neurol 2021 mar 26 doi 101097 wco0000000000000938 online ahead printabstractpurpose review treatments targeting b cells increasingly used patients multiple sclerosis ms review mechanisms action clinical effectiveness safety treatment emphasis recently published studiesrecent findings several monoclonal antibodies targeting surface molecule cd20 b cells approved developed treatment ms overall seem comparable terms strongly suppressing radiological disease activity relapse biology novel approaches include anticd19 antibody therapy treatment oral drugs targeting brutons tyrosine kinase btk main safety issue persistent b cell depletion increased risk infections possibly including increased risk severe covid19 vaccine responses also blunted patients treated anticd20 antibodies lower doses longer infusion intervals may sufficient control disease activity whether might also improve safety treatment increase vaccination responses remains determinedsummary available data support widespread use therapies targeting b cells ms whether novel approaches targeting cd19 btk will advantages compared anticd20 antibody therapy remains established furthermore trials investigating alternative dosing regimens anticd20 antibody treatment warrantedpmid33782253 doi101097 wco0000000000000938,0.0
correspondence humoral immune response covid19 mrna vaccine patients multiple sclerosis treated highefficacy diseasemodifying therapies ther adv neurol disord 2021 may 31 1417562864211019567 doi 101177 17562864211019567 ecollection 2021no abstractpmid34104219 pmcpmc8170321 doi101177 17562864211019567,0.0
astrocytes multiple sclerosisessential constituents diverse multifaceted functions int j mol sci 2021 may 31 22 11 5904 doi 103390 ijms22115904abstractin multiple sclerosis ms astrocytes respond inflammatory stimulation early robust process morphological transcriptional biochemical functional remodeling recent studies utilizing novel technologies samples ms patients animal model ms experimental autoimmune encephalomyelitis eae exposed detrimental beneficial part contradictory functions heterogeneous cell population review summarize various roles astrocytes recruiting immune cells lesion sites engendering inflammatory loop inflicting tissue damage roles astrocytes suppressing excessive inflammation promoting neuroprotection repair processes also discussed pivotal roles played astrocytes make attractive therapeutic target improved understanding astrocyte function diversity mechanisms regulated may lead development novel approaches selectively block astrocytic detrimental responses enhance protective propertiespmid34072790 doi103390 ijms22115904,0.0
brain stimulation attention deficits traumatic brain injury literature review feasibility study background traumatic brain injury disturbances attentional processes direct negative effect functional recovery return complex activities date good attention remediation treatment available primary objective review pilot study provide overview research evidence evaluate feasibility implementing tdcs protocol improve attention disorders patients mild complicated severe subacute tbi hospitalized inpatient rehabilitation facility secondary objective extract preliminary data observational information participants response treatmentmethodsparticipants recruited consecutive series patients admitted tbi unit subspecialized regional rehabilitation center received 20min tdcs stimulation 3 times week 3 weeks neuropsychological evaluation performed intervention collected participants sociodemographic clinical characteristics well information satisfaction tolerability adverse effectsresultsone hundred sixtyfour patients admitted september 2018 january 2020 one hundred fiftyeight excluded 6 patients presumed attentional deficits enrolled none completed protocol intended major side effects occurredconclusionnoninvasive brain neurostimulation promising enhance attention deficits patients tbi implementation tdcs protocol fulfill purpose intensive inpatient rehabilitation center limitations made recommendations facilitate implementation similar projects futuretrial registrationisrctn isrctn55243064 registered 14 october 2020retrospectively registered,0.0
clinical genetic qualityoflife study cohort adult patients tuberous sclerosis background objectivetuberous sclerosis ts condition whose manifestations childhood extensively described whose presentation adults less well known study describes clinical genetic characteristics therapeutic management quality life cohort adult patients ts comparative study characteristics patients diagnosed childhood adulthood also carried outmaterial methodsthis observational retrospective crosssectional study included large cohort adult patients 16 years old followed 5 years specific rare diseases unitresultsfiftyseven patients diagnosis tuberous sclerosis included 50 diagnosed adults mean age patients 42 years 2086 central nervous system main area affected 97 followed skin 807 kidneys 73 frequent genetic alteration mutation tsc2 gene 477 among patients diagnosed adulthood less neurological involvement less frequency epileptic seizures 308 vs 6079 patients diagnosed childhood astrocytomas 38 vs 536 less intellectual disability 115 vs 714 less expressiveness condition 42 patients treated mtor pathway inhibitors presence angiomyolipoma main indication qualityoflife analysis means summary indices scores average spanish population 4742 sd 982 physical health scale 4561 sd 799 mental health scale versus 50 sd 10 general populationconclusionsup 50 adult patients ts diagnosed adulthood condition less severe less frequent epileptic seizures intellectual disability 42 require treatment mtor inhibitors cases due presence amls quality life adult patients ts diminished compared general population,0.0
longterm disability trajectories relapsing multiple sclerosis patients treated early intensive escalation treatment strategies ther adv neurol disord 2021 may 31 1417562864211019574 doi 101177 17562864211019574 ecollection 2021abstractbackground aims consensus exists aggressively treat relapsingremitting multiple sclerosis rrms timing treatment objective study evaluate disability trajectories rrms patients treated early intensive treatment eit moderateefficacy treatment followed escalation higherefficacy disease modifying therapy esc methods rrms patients 5year followup 3 visits disease modifying therapy dmt start selected italian ms registry eit group included patients received first dmt fingolimod natalizumab mitoxantrone alemtuzumab ocrelizumab cladribine esc group patients received high efficacy dmt 1 year glatiramer acetate interferons azathioprine teriflunomide dimethylfumarate treatment patients 11 propensity score ps matched characteristics first dmt disability trajectories evaluated applying longitudinal model repeated measures effect early versus late start highefficacy dmt assessed mean annual expanded disability status scale edss changes compared baseline values deltaedss eit esc groupsresults study cohort included 2702 rrms patients ps matching procedure produced 363 pairs followed median interquartile range 85 65117 years mean annual deltaedss values significantly p 002 higher esc group compared eit group particular mean deltaedss differences two groups tended increase 01 001019 p 003 1 year 030 007053 p 0009 5 years 067 031103 p 00003 10 yearsconclusion results indicate eit strategy effective esc strategy controlling disability progression timepmid34104220 pmcpmc8170278 doi101177 17562864211019574,0.0
targetable nanoparticle baf312 crgdcapnp represses tumor growth angiogenesis downregulating s1pr1 pstat3 vegfa axis triplenegative breast cancer background overexpressed vascular endothelial growth factor vegfa phosphorylated signal transducer activator transcription 3 pstat3 cause unrestricted tumor growth angiogenesis breast cancer brca especially triplenegative breast cancer tnbc hence novel treatment strategy urgently neededresultswe found sphingosine 1 phosphate receptor 1 s1pr1 can regulate pstat3 vegfa database showed s1pr1 highly expressed brca causes poor prognosis patients interrupting expression s1pr1 inhibit growth human breast cancer cells mcf7 mdamb231 suppress angiogenesis human umbilical vein endothelial cells huvecs via affecting s1pr1 pstat3 vegfa axis siponimod baf312 selective antagonist s1pr1 inhibits tumor growth angiogenesis vitro downregulating s1pr1 pstat3 vegfa axis prepared phsensitive tumortargeted shellcore structure nanoparticles hydrophilic peg2000 modified cyclic argglyasp crgd formed shell hydrophobic dspe formed core cap calcium phosphate ions adsorbed onto shell nanoparticles used deliver baf312 baf312 crgdcapnps size potential nanoparticles 1099 1002 nm 106 0056 mv incorporation efficacy baf312 814 results confirmed baf312 crgdcapnp dramatically inhibit tumor growth angiogenesis vitro mdamb231 tumorbearing mice via downregulating s1pr1 pstat3 vegfa axisconclusionsour data suggest potent role baf312 crgdcapnps treating brca especially tnbc downregulating s1pr1 pstat3 vegfa axisgraphic abstract,0.0
intermediate cd14+cd16+monocyte subpopulation plays role ivig responsiveness children kawasaki disease background kawasaki disease kd acute selflimited febrile illness unknown cause intravenous immunoglobulin ivig resistance related greater risk permanent cardiac complications aimed determine correlation monocytes phenotype kd relation ivig responsiveness childrenmaterials methods study cohort included 62 patients diagnosed kd 20 non febrile healthy controls nfc 15 febrile controls ofc enrolled patients blood taken least 4 times laboratory tests performed addition subtypes monocytes characterized via flow cytometryresultsthe numbers intermediate monocytes significantly lower ivigresistant group compared ivigresponsive group ivig infusion p 00001 infusion intermediate monocytes decreased responsive group trend increase observed resistant group intermediate monocytes significant logistic regression adjusted 0001 p value 003conclusionscd14 + cd16 + intermediate monocyte may play important role ivig responsiveness among kd children low starting levels intermediate monocytes followed dramatic increase postivig infusion acute phase kd associated ivigresistance functional studies intermediate monocyte may help reveal pathophysiology,0.0
disruption orbitofrontalhypothalamic projections murine als model human patients background increased catabolism recently recognized clinical manifestation amyotrophic lateral sclerosis als hypothalamic systems shown involved metabolic dysfunction als exact extent hypothalamic circuit alterations als yet determined explored integrity largescale corticohypothalamic circuits involved energy homeostasis murine models als patientsmethodsthe raav2based largescale projection mapping image analysis pipeline based wholebrain ilastik software suites used identify quantify projections forebrain lateral hypothalamus sod1 g93a als mouse model hypermetabolic fusnls als mouse model normometabolic 3 t diffusion tensor imaging dti magnetic resonance imaging mri performed 83 als 65 control cases investigate cortical projections lateral hypothalamus lha alsresultssymptomatic sod1 g93a mice displayed expansion projections agranular insula ventrolateral orbitofrontal secondary motor cortex lha findings reproduced independent cohort using different analytic approach contrast fusnls als mouse model hypothalamic inputs insula orbitofrontal cortex maintained projections motor cortex lost dtimri data confirmed disruption orbitofrontalhypothalamic tract als patientsconclusionthis study provides converging murine human data demonstrating selective structural disruption hypothalamic inputs als promising factor contributing origin hypermetabolic phenotype,0.0
significance covid19 immunological status severe neurological complications multiple sclerosisa literature review int j mol sci 2021 may 31 22 11 5894 doi 103390 ijms22115894abstractsarscov2 coronavirus 2019 covid19 responsible pandemic started december 2019 addition typical respiratory symptoms virus also causes severe complications including neurological ones diagnostics serological polymerase chain reaction tests useful detecting past infections can also predict response vaccination now believed immune mechanism rather direct viral neuroinvasion responsible neurological symptoms reason important assess presence antibodies serum also cerebrospinal fluid csf especially case neurocovid particular group patients people multiple sclerosis ms whose diseasemodifying drugs weaken immune system lead unpredictable serological response sarscov2 infection based available data article summarizes current serological information concerning covid19 csf patients severe neurological complications mspmid34072715 doi103390 ijms22115894,0.0
can rheumatologists stop causing demyelinating disease abstractbackgroundperhaps informative experiments human disease clinical trials notably responses specific therapies can highlyinformative help understand disease pathogenesis reagents inhibit variety different autoimmune conditions cd20 memory b cell depleters active multiple sclerosis ms rheumatoid arthritis ra conditions suggesting influences common immune mechanisms different diseases however notable exception seemed use tumour necrosis factor tnf inhibitors limits ra yet seem rarely trigger demyelination induce ms first seen tnfinhibiting monoclonal antibodies tnfreceptorimmunoglobulin fusion proteins however also seen tyrosine janus kinase inhibitors inhibit ra yet induce demyelinating disease individualspurposeto provide overview b cell centric perspective may underpin biology links arthritis treatments development demyelinating diseaseconclusionsit apparent disease modifying antirheumatoid drugs cause demyelination share number common features agents tend inhibit tnfreceptor signalling augment exhibit limited inhibitor activity classswitched memory b cells importantly appear relatively excluded central nervous system cns will thus target ectopic b cell follicles cns unlike occurring peripheral autoimmunity seen antitnf treatments ra agents ibudilast janus kinase inhibitors inhibit tnf clearly penetrate cns appear induce demyelination may even neuroprotective remains established whether selection development cns penetrant agents may avoid cnscomplications treatments ra clearly studies warranted,1.0
selfreported diet health outcomes participants ccsvitracking survey study nutrients 2021 may 31 13 6 1891 doi 103390 nu13061891abstractof 1575 participants ccsvitracking survey 475 patients recorded quality life edss outcomes least 2 months selfreported use complementary conventional therapies included diet use drug therapy symptoms quality life mobility analysis included comparing outcomes related different diets within groups adherence ms diet associated greater quality life less disability lower symptom score faster walking speed compared diets alternately participants mediterranean diet region whole 3265 sd 1137 sem 237 p 005 significantly greater qol 60 p 005 lower ms symptom score 3265 1137 p 00029 decline symptoms observed diet groups 3 months dramatic decline observed participants eastern mediterranean diet region main effect withinsubjects factor significant f 3 1056 5595 p 0001 indicating significant differences groupspmid34072860 doi103390 nu13061891,0.0
covid19 vaccination willingness among people multiple sclerosis mult scler j exp transl clin 2021 may 31 7 2 20552173211017159 doi 101177 20552173211017159 ecollection 2021 aprjunabstractbackground hesitancy receive covid19 vaccination major public health concern covid19 vaccine willingness factors contributing willingness adults multiple sclerosis ms unknown administered online survey 1 december 2020 7 january 2021 adults ms estimate covid19 vaccine willingness among adults ms bivariate analysis chisquare testing compared categorical variables associated vaccine willingnessresults 401 respondents 701 willing receive authorized covid19 vaccination available 227 unsure 72 unwilling frequent concern unsure vaccine safety vaccine willingness associated increased perceived personal risk covid19 2 454 p 00001 prior influenza vaccine acceptance 2 976 p 00001 higher educational level 2 502 p 00001 respondents discussed planned discuss covid19 vaccine neurologists 2 643 p 00001 conclusion covid19 vaccination willingness high among people ms nearly 30 either unwilling unsure vaccinated neurologists aware patientcentered factors associated covid19 vaccine willingness address covid19 vaccine safety concerns discussions vaccineunsure ms patientspmid34104472 pmcpmc8172949 doi101177 20552173211017159,0.0
service evaluation experiences patients functional neurological disorders within nhs front neurol 2021 may 31 12656466 doi 103389 fneur2021656466 ecollection 2021abstractprevious research functional neurological disorder fnd shown significant barriers providing patientcentred care however specific research whether patient experiences care fnd meet current standards care study aimed investigate types problems experienced fnd patients whether differed patients multiple sclerosis ms fnd n 40 ms patients n 37 recruited nhs tertiary neurology clinics completed questionnaires experiences health care services significant differences experiences care two patient groups found fnd patients reporting significantly problems diagnosis treatment p 0003 patientcentred care p 0001 relationships healthcare professionals p 0001 accessing community care p 0001 limitations include small sample size specificity single centre crosssectional design results suggest current care fnd patients meeting expected standards longterm neurological conditions highlighting need structured care pathways patientcentred carepmid34135848 pmcpmc8200476 doi103389 fneur2021656466,0.0
longterm clinical immunological effects repeated mesenchymal stem cell injections patients progressive forms multiple sclerosis front neurol 2021 may 31 12639315 doi 103389 fneur2021639315 ecollection 2021abstractbackground mesenchymal stem cells msc shown possess immunomodulatory neurotrophic effects previous trials shown intrathecal intravenous iv administration mscs safe provided indications beneficial clinical effects methods open prospective study evaluate safety longterm clinical immunological effects multiple injections autologous mscs 24 patients activeprogressive ms inclusion mean age patients 470 922 mean edss score 675 068 range 5575 patients initially treated 1 106 mscs kg body weight + iv subsequently additional eight courses mscs intervals 612 months duration trial 4 years results serious treatmentrelated adverse events observed followup period twentytwo 24 patients either stable improved last followup visit ten patients lower baseline edss last followup nine among received 2 treatments one subgroup 2 treatments p 004 mean edss score reduced 675 068 baseline 642 084 last visit median followup period 278 months p 0028 immunological followup showed transient upregulation cd4+cd25+foxp3+ cells downregulation proliferative ability lymphocytes conclusions repeated msc treatments patients progressive ms shown safe short intermediate term induced clinical benefits especially patients treated 2 injections lasted 4 years paralleled shortterm immunomodulatory effects clinical trial registration wwwclinicaltrialsgov identifier nct04823000pmid34135843 pmcpmc8202001 doi103389 fneur2021639315,0.0
effects nogoa receptor repair sciatic nerve injury rats regeneration injured peripheral nerves extremely complex process nogoa neurite outgrowth inhibitora inhibits axonal regeneration interacting nogo receptor myelin sheath central nervous system cns aim study investigate effects nogoa receptor repair sciatic nerve injury rats spraguedawley rats n96 randomly divided 4 groups control group control sciatic nerve transection group model immediate repair group immediate repair delayed repair group delayed repair rats euthanized 1 week 6 weeks operation injured end tissues spinal cord sciatic nerve obtained protein expressions nogoa nogo66 receptor ngr detected immunohistochemistry protein expressions nogoa ngr ras homolog family member rhoa detected western blot 1 week operation pathological changes immediate repaired group less protein expressions nogoa ngr rhoa spinal cord sciatic nerve tissues decreased p005 compared model group 6 weeks pathological changes immediate repair group delayed repair group alleviated protein expressions decreased p005 situation immediate repair group better delayed repair group data suggest expression nogoa receptor increased sciatic nerve injury indicating nogoa receptor play inhibitory role repair process sciatic nerve injury rats,1.0
information needs patients chronic diseases relatives webbased advance care planning qualitative interview study background advance care planning acp enables persons identify preferences future treatment care discuss record review preferences however uptake acp among patients chronic diseases relatively low webbased acp programs can support patients relatives acp however information needs patients relatives acp unknown aim study explore information needs patients chronic disease relatives webbased acpmethodswe conducted semistructured interviews patients chronic diseases relatives home study center three cases patient relative paired since preferred interviewed together asked information search start acp search information search terms use internet content information consider important acp website interviewer asked participants clarify responses interview used thematic analysis analyze interviewees responsesresultswe interviewed nine patients different chronic diseases including amyotrophic lateral sclerosis als multiple sclerosis ms chronic obstructive pulmonary disease copd kidney diseases seven relatives namely partners adult children interviewees aged 24 80 years nine female seven male patients chronic disease relatives mentioned comparable information needs many interviewees indicated use internet search information acp mentioned search terms advance care planning treatment plan disease trajectory names patient associations information needs concerned disease trajectory quality life medical treatment decisions practical support arranging care concept acp guidance acp communication treatment care preferences peer support others chronic diseases information relatives many appreciated encouragement healthcare providers take proactive role acpconclusionswe conclude information needs acp included guidance acp support making decisions medical treatment practical support arranging care recommend adapting webbased acp information information needs patients relatives increase findability uptake usefulness,0.0
clinical practice patterns multiple sclerosis management mexican consensus recommendations abstractbackgroundmultiple sclerosis affects 2 million people clinical decisions performed evidencebased medicine appearance new diseasemodifying therapies changes diagnostic criteria complicates decisionmaking process clinical practiceobjectivesto characterize criteria radiologically isolated syndrome ris clinically isolated syndrome cis relapsingremitting multiple sclerosis rrms mexican neurologists realworld settingmethodsa tworound modified delphi method rand ucla appliedresultsin ris lp spinal cord mri vep included diagnostic testing dmt initiation necessary followup mri within 3 months recommended cis corticosteroid therapy initiated first relapse simple gdenhanced mri mandatory lp selective blood tests nmoigg aqp4 antibodies performed complementary ifn beta ga suitable dmts treating highrisk cis patients rrms begin dmt diagnosis include followup mri patient 2 relapses within 6 months ga oral dmts eligible dmts mild rrms monoclonal antibodiesbased therapy chosen disability present radiological criteria switching dmt included 1 gd+ lesion 2 new t2 lesionsconclusionsalthough many coincidences still many hollows medical attention ms mexico consensus recommendation helpful implement better evidencebased recommendations guidelines realworld setting,0.0
maternal education significant influence progression multiple sclerosis abstractobjectivethe identification potential risk factors disease severity great importance treatment multiple sclerosis influence socioeconomic status progression multiple sclerosis ms sparsely investigated aim investigate socioeconomic status adolescence influences disease progression later lifemethodsa total 1598 patients multiple sclerosis welldefined population norway included detailed information disease progression measured expanded disability status scale edss multiple sclerosis severity score msss combined data socioeconomic factors used residency parental level education patientsnull age 16 exposure secondhand smoking measure socioeconomic status adolescence adjusting variables well use disease modifying treatments prevalence date 010118resultshigh maternal level education patientsnull age 16 significantly associated less pronounced disease progression measured msss coefficient 058 p0015 younger age lower edss disease onset shorter time onset diagnosis significant associations found paternal education level msss use disease modifying treatment prevalence date significantly associated disease progression coefficient 049 p0004 residence current secondhand smoking notconclusionthis study populationbased realworld cohort shows parental level education significant impact timely diagnosis ms addition disease modifying treatment maternal level education also impact disease progression later life,0.0
modern technologies rehabilitation patients multiple sclerosis potential application times covid19 medicina kaunas 2021 may 30 57 6 549 doi 103390 medicina57060549abstractbackground objectives covid19 pandemic required adoption new technologies improve access healthcare unprecedented speed social distancing became mandatory aim systematic review analyze effectiveness using new technologies rehabilitation multiple sclerosis ms patients discuss potential role covid19 pandemic material methods studies identified searching two online databasespubmed web science combinations key words multiple sclerosis ehealth multiple sclerosis virtual reality multiple sclerosis telerehabilitation multiple sclerosis new technologies multiple sclerosis teleexercise used find suitable publications results total 17 studies included although overall number participants studies 904 two studies conducted group thus total 854 participants involved studies included participants diagnosed ms 10 studies participants diagnosed according mcdonald criteria included studies five involved intervention participants home six conducted using xbox kinect seven studies reported adverse outcomes conclusion review proves telerehabilitation effective motivational tool restore maintain physical cognitive function patients ms remote communication technologies seem measures high effectiveness rehabilitating supporting ms patients especially covid19 pandemic traditional rehabilitation option less accessible cases inaccessible patientspmid34070705 doi103390 medicina57060549,0.0
nonparametric propensity score estimating effect interferonbeta glatiramer acetate longterm outcomes multiple sclerosis abstractbackgroundthe observational studies investigated longterm effects interferonbeta glatiramer acetate usually focused progression irreversible disability outcomes number relapses transition secondaryprogressive multiple sclerosis spms rarely studied objective paper estimate effect interferonbeta glatiramer acetate progression irreversible disability transition relapsingremitting multiple sclerosis rrms spms rate relapses 10 yearsmethodsanalyses included 2498 patients confirmed diagnosis rrms followed montral 1977 2016 marginal structural models propensity score treatment censoring used account potential confounding attrition specifically used pooled logistic regression progression irreversible disability transition spms poisson models rate relapsesresults77 subjects female median age rrms diagnosis 35 years hazard progression irreversible disability lower among treated patients untreated patients hr073 95 ci 057094 find evidence association interferonbeta glatiramer acetate rate transition spms either 3month intervals duration treatment patients treated 5 years lower rate relapses compared untreated hr070 95 ci 057086 conclusiontreatment interferonbeta glatiramer acetate suggests beneficial effect progression irreversible disability rate relapses transition spms,0.0
covid19 argentine teriflunomidetreated multiple sclerosis patients first national case series abstractwe report covid19 presentation course outcomes teriflunomidetreated ms patients argentina methods descriptive retrospective multicentre study included ms patients receiving teriflunomide developed covid19 clinical followup reference ms centres also listed nationwide registry results eighteen ms patients teriflunomide treatment eight ms centres developed covid19 mean age 41 2 years 72 female 94 diagnosis relapsingremitting ms 6 presented radiologically isolated syndrome median edss 2 range 055 average time teriflunomide therapy 3 years covid19 diagnosis confirmed nasal swab 61 none required hospitalization completely recovered acutephase within 714 days patients continued teriflunomide therapy covid19 course ms relapses occurred covid19 course conclusion report adds evidence covid19 mild patients receiving teriflunomide therapy continuing teriflunomide therapy sarscov2 infection safe advisable ms patients,0.0
commentary letter can coronavirus disease 2019 covid19 trigger exacerbation multiple sclerosis retrospective study read paper entitled can coronavirus disease 2019 covid19 trigger exacerbation multiple sclerosis retrospective study barzegar et al 2021 great interest believe studies conducted order knowledge identify possible postcovid19 complications patients ms pwms however points like share scientific community regarding study,0.0
coronary sinus atrial septal defects adults past 20years new tokyo hospital case series background isolated coronary sinus cs atrial septal defect asd defined cs unroofed terminal portion without persistent left superior vena cava anomalies defect rare part wide spectrum unroofed cs syndrome urcs recently several reports described finding database new tokyo hospital searched determine incidence defect additionally raise awareness condition findings five patients cs asd underwent surgical repair new tokyo hospital discussedcase presentationthe patients three women two men age range 6377 years patients underwent transthoracic echocardiography computed tomography one underwent magnetic resonance imaging two patients defect found unexpectedly intraoperatively lefttoright shunting apparent three patients preoperatively pulmonarytosystemic blood flow ratio ranged 142 31 following cardiac catheterization oxygen saturation stepup seen right side heart valvular regurgitation seen 4 5 patients different combinations degrees mitral tricuspid aortic valve involvement right atrial ventricular dilation seen 4 5 patients three patients left atrial dilation three patients experienced atrial fibrillation one also experienced paroxysmal ventricular contractions patients underwent surgical repair underwent multiple procedures one patient previously undergone kidney transplantation died approximately 1 year postoperatively remaining four patients currently experiencing good activities daily living without symptomsconclusionscs asd kirklin barrattboyes type iv urcs comprised 13 adult congenital heart surgeries 007 adult openheart surgeries new tokyo hospital 1999 2019 new tokyo hospital cardiac surgery performed mainly patients acquired cardiac disease cs asd rare early diagnosis important well early surgical repair symptomatic patients especially blood access shunts may overload heart case poor prognosis series noteworthy similar cases reported previously,0.0
nonambulatory measures lower extremity sensorimotor function associated walking function multiple sclerosis abstractbackgrounddisease progression multiple sclerosis ms often monitored ambulatory measures nonambulatory sensorimotor measures differentially associate walking measures ms subtypes unknown determined whether characteristic differences relapsingremitting ms rrms progressive ms pms nonms controls lower extremity sensorimotor function clinical walking tasks sensorimotor associations walking function groupmethods18 rrms 13 pms 28 nonms control participants evaluated plantar cutaneous sensitivity vibration perception threshold volts proprioception ankle joint positionmatching dorsiflexion motor coordination rapid foottap count 10s walking function three tests timed 25foot walk t25fw preferred fast speeds s timedupandgo tug s resultsfoottapping p0039 mean difference md 565 taps plantar cutaneous sensation p0026 md1030v differed ms subtypes rrms group faster walking related better proprioceptive function preferred t25fw p0019 root mean square error rmse 194 fast t25fw p0004 rmse165 tug p0001 rmse212 foottap performance preferred t25fw p0033 rmse274 fast t25fw p0010 rmse202 associations observed pms groupconclusionsfoottap performance plantar cutaneous sensitivity ankle proprioception differed ms subtypes lower walking performance associated lower foottapping plantar cutaneous sensitivity rrms pms group result suggests change relationship lower extremity sensorimotor function walking performance pms subtype,0.0
validation obstructive sleep apnea symptom inventory persons multiple sclerosis abstractbackgroundimproved screening obstructive sleep apnea osa enhance multiple sclerosis ms clinical care yet utility current screening tools osa yet evaluated persons multiple sclerosis pwms objectivesthe stopbang questionnnaire 8item screening tool osa commonly used nonms samples aim study assess validity stopbang pwmsmethodsstopbang polysomnography data analyzed n 200 pwms sensitivity specificity positive negativepredictive value ppv npv calculated receiving operating characteristic roc curves stopbang threshold score polysomnographyconfirmed osa diagnosis three apnea severity thresholds mild moderate severe resultsnearly 70 stopbang score 3 78 osa stopbang threshold score 3 provided sensitivities 87 91 detect moderate severe osa respectively npv 84 95 identify pwms without moderate severe osa respectively sensitivity detect milder forms osa 76 npv identify persons without milder forms osa 40conclusionthe stopbang questionnaire effective tool screen moderate severe osa pwms may insufficient exclude mild osa,0.0
correcting gut dysbiosis can ameliorate inflammation promote remyelination multiple sclerosis commentary basic research uncovered surprising connections gut microbiota essential functions body exciting findings offer fascinating perspectives treatment human diseases clinical application however lags behind progress made basic understanding microbiota sobering fact provides background current controversy laura calvobarreiro colleagues argue therapeutic modulation microbiota can regulate peripheral immune responses also induce remyelination neuroprotection1 optimistic view supported proponents studies animal models2 3 contrast christopher mcmurran points remedying dysbiosis can improve inflammation demyelination animal models4 sceptical view based observation modulation microbiota minimal impact remyelination toxicinduced lysolecithin cuprizone mouse models5 taken together convincing evidence modulation microbiota can ameliorate experimental autoimmune responses also firm evidence microbiota regulates neurobiological microglial functions via gutbrain axis6 less clear however whether microbiota direct influence myelination urgent challenges human microbiota research push field towards clinical translation first number studied subjects needs drastically increased many published studies indicate multiple sclerosis ms indeed dysbiosis commensal microbiota7 however studies based relatively small cohorts lacking rigorous controls regard international ms microbiome study imsms takes big step forward aiming collect large number samples people ms household members serve controls8 large study help characterize currently somewhat vaguely described state dysbiosis second order identify diseaserelevant microbes essential candidate bacteria tested functional diseasepromoting capacity can achieved example gnotobiotic mouse models colonization genetically engineered autoimmuneprone germfree mice humanderived microbiota helps distinguish diseasepromoting protective bacteria9 10 identification msrelevant microbial signature open new doors rational therapy declaration conflicting interests author s declared potential conflicts interest respect research authorship publication article,1.0
underpinnings verbal fluency multiple sclerosis summarythe cognitive language processes underlying verbal fluency remain unclear cognitive processes related memory executive functioning associated category letter verbal fluency less studied aspects language ability also related discuss contribution recent study lebkuecher colleagues 2021 role language verbal fluency data studies evaluating cognitive neuroimaging correlates verbal fluency ms,0.0
protein nanoparticles drug delivery animal protein plant proteins protein cages albumin nanoparticles abstractin article will describe properties albumin biological functions types sources can used produce albumin nanoparticles methods producing albumin nanoparticles therapeutic applications importance albumin nanoparticles production pharmaceutical formulations view increasing use abraxane approval use treatment several types cancer final stages clinical trials cancers evaluate compare effectiveness conventional non formulations chemotherapy paclitaxel paid article will examine role importance animal proteins nano medicine various benefits biomolecules preparation drug delivery carriers characteristics plant protein nano carriers protein nano cages potentials diagnosis treatment finally advantages disadvantages protein nanoparticles mentioned well methods production albumin nanoparticles therapeutic applications importance albumin nanoparticles production pharmaceutical formulations,0.0
correcting gut dysbiosis can ameliorate inflammation promote remyelination multiple sclerosis basic research uncovered surprising connections gut microbiota essential functions body exciting findings offer fascinating perspectives treatment human diseases clinical application however lags behind progress made basic understanding microbiota sobering fact provides background current controversylaura calvobarreiro colleagues argue therapeutic modulation microbiota can regulate peripheral immune responses also induce remyelination neuroprotection1 optimistic view supported proponents studies animal models2 3 contrast christopher mcmurran points remedying dysbiosis can improve inflammation demyelination animal models4 sceptical view based observation modulation microbiota minimal impact remyelination toxicinduced lysolecithin cuprizone mouse models5taken together convincing evidence modulation microbiota can ameliorate experimental autoimmune responses also firm evidence microbiota regulates neurobiological microglial functions via gutbrain axis6 less clear however whether microbiota direct influence myelinationwhat urgent challenges human microbiota research push field towards clinical translation first number studied subjects needs drastically increased many published studies indicate multiple sclerosis ms indeed dysbiosis commensal microbiota7 however studies based relatively small cohorts lacking rigorous controls regard international ms microbiome study imsms takes big step forward aiming collect large number samples people ms household members serve controls8 large study help characterize currently somewhat vaguely described state dysbiosis second order identify diseaserelevant microbes essential candidate bacteria tested functional diseasepromoting capacity can achieved example gnotobiotic mouse models colonization genetically engineered autoimmuneprone germfree mice humanderived microbiota helps distinguish diseasepromoting protective bacteria9 10 identification msrelevant microbial signature open new doors rational therapy,1.0
correcting gut dysbiosis can ameliorate inflammation promote remyelination multiple sclerosis yes although aetiology multiple sclerosis ms unknown genetic environmental factors recognized contribute development disease recently gut microbiota emerged novel environmental risk factor primarily result research data experimental autoimmune encephalomyelitis eae 1 experimental model ms ms patients2 even clear gut microbiome signature identified studies ms patients confirm presence characteristic dysbiosis intestine clinical course disease3recent evidence shown close relationship intestinal microbiota hosts immune system makes sense gut dysbiosis may play relevant role dysregulation immune response possibly representing risk development ms msrelated gut dysbiosis linked ms distinctive immune responses 4 pathogenesis progression however experimental data support idea bacterial strains far harmful beneficial impact ms thus promotion beneficial microorganisms developed important therapeutic strategy ms focused immunomodulatory properties antiinflammatory regulatory microbiota modulation can achieved different approaches faecal transplantation probiotic prebiotic administration diet modification among othersprobioticbased therapies shown immunomodulatory effects can reverse immune disturbances turn modulate progression eae therapeutic effect related inhibition th1 th17 responses enhancement immunoregulatory responses regulatory t treg cells another potential mechanism efficacy probiotic administration decrease production proinflammatory cytokines il17 ifn tnf il12 increase antiinflammatory ones il4 il10 tgf 3 addition modulating adaptive immune responses microbiota can also modify function innate immune cells mainly dendritic cells dcs macrophages shifting response towards tolerogenic one5 6shortchain fatty acids scfas major metabolites produced fermentative activity gut microbiota several studies showed considerable reduction scfa producers ms gut evidence immunomodulatory effects mediated gut microbiota least partially induced scfas demonstrated modulate adaptive innate immune responses regulate gut immunity inducing treg cells can also regulate dcs induce production il10 retinoic acid also lead expansion treg cells furthermore treg cells shown exert neuroprotection increasing remyelination differentiation oligodendrocytes7 thus gut microbiota can indirectly promote remyelination neuroprotectionon hand association gut dysbiosis central nervous system cns diseases neurodegenerative psychiatric neuroimmune disorders established repair inflammatory demyelinated lesions ms requires clearance myelin debris microglia macrophages also switch proinflammatory antiinflammatory lesion environment regarding latter aspect microglia known secrete regenerative factors essential myelin repair thus bidirectional microbiotagutbrain axis relevant impact ms pathogenesis modulation cns functions maturation function microglia limitation astrocyte pathogenicity expression myelin genes8 evidence support treatment probiotics relevant effects cns functions9 addition scfas can directly suppress demyelination enhance remyelination inducing differentiation immature oligodendrocytes10in summary microbiota modulation can regulate peripheral immune responses generation tolerogenic mechanisms production antiinflammatory cytokines thus limiting autoimmune response occurs ms also can modulate cns functions inducing remyelination neuroprotection altogether data point correction gut dysbiosis potential therapeutic approach improve neuroinflammation potentiate neuroprotection ms,1.0
investigation correlation mildly deleterious mtdna variations clinical progression multiple sclerosis abstractbackgroundevidence suggests mitochondrial dna mtdna variation population level may influence susceptibility clinical progression multiple sclerosis ms objectiveto determine mtdna population variation linked clinical progress msmethodsusing complete mtdna sequences 217 ms patients applied new variant loadnull model designed framework examine role mtdna variation context complex clinical diseaseresultsno significant association detected mtdna variant loadnulland clinical measures progressionconclusionour results suggest mtdna population variation play substantial role clinical progression ms however modest effects effects subgroup patients entirely excluded results exclude possibility detecting association variation strictly quantified variables obtained histopathologicallystained specimens results illustrate methodnulls applicabilityto disease phenotypes,0.0
agedependent favorable visual recovery despite significant retinal atrophy pediatric mogad much retina really need see well background investigate agerelated severity patterns retinal structural damage functional visual recovery pediatric adult cohorts myelin oligodendrocyte glycoprotein antibodyassociated disease mogad optic neuritis methodsall mogad patients 5 participating centers included patients initial manifestation 18 years included pediatric mogadped cohort patients 18 years adult mogadadult cohort patients mogad examinations least 6 months onset included analyses using spectral domain optical coherence tomography sdoct acquired peripapillary retinal nerve fiber layer thickness prnfl volumes combined ganglion cell inner plexiform layer gcipl high 25 lowcontrast visual acuity hcva lcva visualevoked potentials vep obtainedresultstwenty mogadped 10337 years 30 mogad eyes 39 mogadadult 349116 years 42 mogad eyes patients included average number episodes per eye similar groups 1813 2017 pediatric adult mogad led pronounced neuroaxonal retinal atrophy prnfl 631187 643229 m gcipl 042009 044013 mm3 respectively moderate delay vep latencies 1179107 1180145 ms contrast visual acuity substantially better children hcva 51493 vs 350206 raw letters p0001 lcva 228146 vs 135164 p0028 complete visual recovery hcvalogmar 00 occurred 733 mogadped 31 mogadadults eyes 33 31 demonstrated moderate severe logmar 05 visual impairment independent retinal atrophy age onset significantly correlated visual outcomeconclusionpediatric mogad showed better visual recovery adult mogad despite profound almost identical neuroaxonal retinal atrophy agerelated cortical neuroplasticity may account substantial discrepancy structural changes functional outcomes,1.0
protective effect alamandine doxorubicininduced nephrotoxicity rats background study aimed evaluate protective effects alamandine new member angiotensin family doxorubicin dox induced nephrotoxicity ratsmethodsrats intraperitoneally injected dox 3750 mg kg week reach total cumulative dose 15 mg kg day 35 alamandine 50 g kg day administered rats via miniosmotic pumps 42 days end experiment rats placed metabolic cages 24 h water intake urine output measured scarification rats serum kidney tissues collected biochemical histopathological immunohistochemical studies carried outresultsdox administration yielded increases proinflammatory cytokines including interleukin il 1 il6 profibrotic proteins transforming growth factor tgf proinflammatory transcription factor nuclear kappa b nfb kidney malondialdehyde mda creatinine clearance blood urea nitrogen bun water intake hand doxtreated group exhibited decreased renal superoxide dismutase sod renal glutathione peroxidase gpx activity urinary output alamandine cotherapy decreased effects confirmed histopathology immunohistochemical analysisconclusionsthe results suggest alamandine can prevent nephrotoxicity induced dox rats,0.0
author response correspondence humoral immune response covid19 mrna vaccine patients multiple sclerosis treated highefficacy diseasemodifying therapies ther adv neurol disord 2021 may 29 1417562864211020082 doi 101177 17562864211020082 ecollection 2021no abstractpmid34104221 pmcpmc8165862 doi101177 17562864211020082,0.0
impact diverse ion channels regulatory t cell functions cell physiol biochem 2021 may 28 55 s3 145156 doi 1033594 000000375abstractthe population regulatory t cells tregs critical immunological selftolerance homeostasis proper ion regulation contributes treg lineage identity regulation effector function identified ion channels include ca2+ releaseactivated ca2+ transient receptor potential p2x volumeregulated anion k+ channels kv13 kca31 ion channel modulation represents promising therapeutic approach treatment autoimmune diseases rheumatoid arthritis multiple sclerosis review summarizes studies genetargeted mice pharmacological modulators affecting treg number function furthermore participation ion channels illustrated power future research possibilities discussedpmid34043301 doi1033594 000000375,0.0
contribution astrocytes neurovascular coupling spinal cord rat abstractfunctional magnetic resonance imaging fmri spinal cord relies integrity neurovascular coupling nvc infer neuronal activity hemodynamic changes astrocytes key component cerebral nvc role spinal nvc unclear objective study examine whether inhibition astrocyte metabolism fluorocitrate alters spinal nvc 14 rats local field potential lfp spinal cord blood flow scbf recorded simultaneously lumbosacral enlargement noxious stimulation sciatic nerve local administration fluorocitrate n 7 saline n 7 fluorocitrate significantly reduced scbf responses p 0001 lfp amplitude p 022 compared saline accordingly nvc altered fluorocitrate compared saline p 001 results support role astrocytes spinal nvc implications spinal cord imaging fmri conditions astrocyte metabolism may altered,0.0
metformin reverses hashimoto#39 s thyroiditis regulating key immune events front cell dev biol 2021 may 28 9685522 doi 103389 fcell2021685522 ecollection 2021abstractbackground hashimotos thyroiditis ht common autoimmune disease characterized high levels thyroid peroxidase antibody tpoab thyroid globulin antibody tgab well infiltration lymphocytes thyroid recent years metformin proven effective variety autoimmune diseases systemic lupus erythematosus rheumatoid arthritis multiple sclerosismethods study systematically explored therapeutic effect metformin ht underlying mechanism comprehensively utilizing methods including animal model vitro cell culture differentiation mrna sequencing 16s rrna sequencingfindings found metformin indeed therapeutic effect mice ht mainly reducing tgab lymphocyte infiltration thyroid tissue addition metformin also significantly suppressed number function th17 cells m1 macrophages polarization ht mice furthermore metformin can inhibit differentiation function th17 vitro results mrna sequencing thyroid tissue illustrated therapeutic effect metformin ht mainly achieved regulating immune pathways 16s rna sequencing intestinal flora found intestinal flora ht mice differs significantly normal mice also altered metformin treatmentinterpretation experiments provided preliminary theoretical basis clinical application metformin treatment htpmid34124070 pmcpmc8193849 doi103389 fcell2021685522,0.0
immunoglobulin g4related periodontitis case report review literature background immunoglobulin g4related disease igg4rd chronic inflammatory systemic disease unknown etiology can affect one multiple organs disease can mimic many infectious inflammatory diseases mainly causing organ enlargement hyperplasia diagnosis primarily relies clinical serologic histological features lymphoplasmacytic infiltrates storiform fibrosis obliterative phlebitis igg4 + plasma cells report rare case igg4related periodontitis review relevant literaturescase presentationa 38yearold chinese man visited department periodontics gingival enlargement loose teeth tooth loss patient poor oral hygiene large amount calculus gingivae edematous deep periodontal pockets attachment loss panoramic radiography showed alveolar bone loss serologic examination showed igg 2370 g l igg4 concentration 2800 g l significant lymphoplasmacytic infiltration storiform pattern fibrosis mitotic figures hematoxylin eosin staining immunohistochemical staining showed 10 scattered igg4positive plasma cells highpower field patient diagnosed igg4related periodontitis received course corticosteroids periodontal therapy enlargement significantly improved without recurrenceconclusionigg4rd oral maxillofacial region mainly involves salivary glands rare case characterized enlarged gingivae differential diagnosis igg4rd based clinical features serologic igg4 histopathological examinations corticosteroid therapy effective igg4rd patients taken together hope case report literature review can help dentists improve understanding igg4rd,0.0
relapse recovery multiple sclerosis effect treatment contribution longterm disability mult scler j exp transl clin 2021 may 28 7 2 20552173211015503 doi 101177 20552173211015503 ecollection 2021 aprjunabstractbackground although recovery relapses ms appears contribute disability largely ignored treatment endpoint disability predictorobjective identify demographic clinical predictors relapse recovery first 3 years examine contribution 10year disability mri outcomesmethods relapse recovery retrospectively assessed 360 patients ms using return expanded disability status scale edss functional system scale neurologic signs baseline least 6 months onset univariate multivariable models used associate recovery demographic clinical factors predict 10year outcomesresults recovery relapses first 3 years better patients younger diseasemodifying treatment longer disease duration without bowel bladder symptoms every incomplete recovery 10year edss increased 06 10year timed 25foot walk increased 05 s outcomes also higher older age higher baseline bmi tenyear mri brain atrophy associated older age mri lesion volume associated smokingconclusions early initiation diseasemodifying treatment ms associated improved relapse recovery turn prevented longterm disabilitypmid34104471 pmcpmc8165535 doi101177 20552173211015503,0.0
lifestyle factors outcomes paediatriconset multiple sclerosis paediatriconset multiple sclerosis inflammatory demyelinating disease cns comprises 210 multiple sclerosis cases characterised high mri lesion burden 1 high relapse frequency altered trajectory agerelated brain growth 2 3 fatigue depressive symptoms reported 75 children multiple sclerosis 50 can cognitive deficits progressive worsening time 4 growing evidence suggests factors diet physical activity body habitus can mediate disease outcomes 5 relationship factors might explained microbiome,1.0
kappafree light chains csf predict early multiple sclerosis disease activity neurol neuroimmunol neuroinflamm 2021 may 28 8 4 e1005 doi 101212 nxi0000000000001005 print 2021 julabstractobjective investigate whether free light chain flc index predicts multiple sclerosis ms disease activity independent demographics clinical characteristics mri findingsmethods patients early ms csf serum sampling disease onset followed 4 years baseline age sex type symptoms corticosteroid treatment number t2 hyperintense t2l contrastenhancing t1 lesions cels mri determined followup occurrence second clinical attack start diseasemodifying therapy dmt registered flcs measured nephelometry flc index calculated csf flc serum flc albumin quotientresults total 88 patients mean age 33 10 years female predominance 68 included 38 43 patients experienced second clinical attack followup multivariate cox regression analysis adjusting age sex t2l cel disease followup duration administration corticosteroids baseline dmt followup revealed flc index predicts time second clinical attack patients flc index 100 median value 147 baseline twice high probability second clinical attack within 12 months patients low flc index median 28 within 24 months chance patients high flc index 4 times high patients low flc index median time second attack 11 months patients high flc index whereas 36 months low flc indexconclusion high flc index predicts early ms disease activityclassification evidence study provides class ii evidence patients early ms high flc index independent risk factor early second clinical attackpmid34049994 doi101212 nxi0000000000001005,0.0
human pluripotent stem cellderived brain organoids vitro models studying neural disorders cancer abstractthe sheer complexities brain resource limitation human brain tissue greatly hamper understanding brain disorders cancers recently developed threedimensional 3d brain organoids bos selforganized spontaneously differentiated human pluripotent stem cells hpscs vitro exhibit similar features cell type diversity structural organization functional connectivity developing human brain based characteristics hpscderived bos hpdbos provide new opportunities recapitulate complicated processes brain development neurodegenerative disorders brain cancers vitro review will provide overview existing bo models summarize applications technology modeling neural disorders cancers furthermore will discuss challenges associated use vitro models disease modeling potential future direction,0.0
novel mutation tnfrsf11a gene causes pediatric osteopetrosis case report background osteopetrosis rare inherited bone disorder affected individual osteoclast disfunction increasing bone density surgery taken histological examination specimen evidence malignancy found finally xray gene detection lead diagnosiscase presentationwe report 10yearold girl two years history pus rhinorrhea nasal obstruction smelly nose diagnosed treated sinusitis symptoms recurrent ten months ago afflicted persistent swelling broken skin right cheek laboratory findings showed normal surgery resected right gingiva right nasal mucosa right facial tissue biopsies histological examination showed proliferation granulation tissue chronic inflammatory mucosa xrays showed generalized sclerosis genetic analysis strongly supported novel mutation tnfrsf11a gene caused osteoporosis found novel mutation c1196c g ps399x exon 9 tnfrsf11a tnfrsf11a gene encodes rank fundamental osteoclast formationconclusionosteopetrosis rare genetic bone disease characterized increased bone density bone resorption failure diagnosis based xray gene analyze osteoclasts bonerelated cells derived hematopoietic cell lines since osteoclasts arise hematopoietic progenitor cell monocytic lineage defect can corrected hematopoietic stem cell transplantation hsct better understanding pathological situation pathogenesis important plan appropriate immunotherapy benefit,0.0
epidemiology covid19 msrelated characteristics national sample people ms china front neurol 2021 may 28 12682729 doi 103389 fneur2021682729 ecollection 2021abstractfew studies focused immune status disease activity ms patients coronavirus disease 2019 covid19 pandemic aim study investigate immune status covid19 infection attacks ms patients pandemic online questionnaire covid19 infection ms attack ms treatment pandemic administered 525 ms patients registered hospital database january 1 2011 june 1 2020 384 responded 361 patients included final analysis pandemic 421 361 patients 650 234 patients immunotherapies exposed teriflunomide compared patients didnt receive treatment patients exposed dmts significantly lower levels neutrophils p 001 immunoglobulin g p 001 patients exposed immunosuppressants significantly lower levels immunoglobulin g p 005 80 patients followed effective protective measures none 361 ms patients cohort contracted covid19 patients whose treatment disrupted significantly higher annualized relapse rate arr pandemic p 001 arr patients continuous treatment without treatment remained unchanged pandemic risk ms attack due treatment disruption possibly outweighs risk covid19 infection preventive measures ms treatment maintenance might necessarypmid34122322 pmcpmc8193356 doi103389 fneur2021682729,0.0
maternal multiple sclerosis risk factor neurodevelopmental disorders offspring mult scler j exp transl clin 2021 may 28 7 2 20552173211017301 doi 101177 20552173211017301 ecollection 2021 aprjunabstractbackground childhood neurodevelopmental disorders ndds including specific learning disorders sld attention deficit hyperactivity disorder adhd autism spectrum disorder asd pathogenically linked familial autoimmunity maternal immunemediated diseases pregnancyobjective studied maternal ms potential risk factor ndds occurrence offspringmethods ms control mothers subjected questionnaires ascertain ndd diagnosis progeny occurrence autoimmune neurodevelopment disorders families suspected ndd cases evaluated confirm rule diagnosisresults 322 ms women 206 64 361 children 27 75 diagnosed ndd 11 adhd 22 asd 67 sld nddrisk offspring associated family history autoimmunity ndds ms nonms mother families r 075 p 0005 whereas associated maternal msconclusions first time demonstrate maternal ms predispose children higher risk ndd mechanistic view suggest intrinsic organspecific nature ms impair motherchild crosstalk decidua influence fetal neurodevelopmentpmid34104473 pmcpmc8165841 doi101177 20552173211017301,0.0
autoimmunomic signatures aging agerelated neurodegenerative diseases associated brain function ribosomal proteins front aging neurosci 2021 may 28 13679688 doi 103389 fnagi2021679688 ecollection 2021abstractbiological aging complex process featured declined function cells tissues including immune system consequence aging affects expression development autoantibodies autoreactive t cells can seen sum autoimmunome individual study analyzed whether sets autoimmune features associated specific phenotypes form autoimmunomic signatures related age neurodegenerative diseases autoantibody profile data healthy subjects patients geo database used explore autoimmunomic signatures aging three neurodegenerative diseases including parkinsons disease pd alzheimer disease ad multiple sclerosis ms results demonstrate autoimmunomic signature aging featured undulated increase igg autoantibodies associated learning behavior consistent increase igg autoantibodies related ribosome translation autoimmunomic signature aging also associated agerelated neurodegenerative diseases intriguingly differential expressionsliding window analysis deswan identified three waves changes autoantibodies aging age 30 50 62 years respectively furthermore igg autoantibodies particular ribosomal proteins used prediction markers aging agerelated neurodegenerative diseases therefore study first time uncovers comprehensive autoimmunomic signatures aging agerelated neurodegenerative diseasespmid34122052 pmcpmc8192960 doi103389 fnagi2021679688,0.0
epidemiology chronic ankle instability perceived ankle instability systematic review background chronic ankle instability developing ankle sprain one common sports injuries besides ankle issue chronic ankle instability can also cause additional injuries investigating epidemiology chronic ankle instability essential step develop adequate injury prevention strategy however epidemiology chronic ankle instability remains unknown therefore purpose study investigate epidemiology chronic ankle instability valid reliable selfreported tools active populationsmethodsan electronic search performed pubmed web science july 2020 inclusion criteria articles peerreviewed published 2006 2020 using one valid reliable tools evaluate ankle instability determining chronic ankle instability based criteria international ankle consortium including outcome epidemiology chronic ankle instability risk bias included studies evaluated adapted tool sports injury review methodresultsafter removing duplicated studies 593 articles screened eligibility twenty fulltexts screened finally nine studies included assessing 3804 participants total participants 15 32 years old represented soldiers students athletes active individuals history ankle sprain prevalence chronic ankle instability 25 ranging 7 53 prevalence chronic ankle instability within participants history ankle sprains 46 ranging 9 76 five included studies identified chronic ankle instability based standard criteria four studies applied adapted exclusion criteria conduct study five nine included studies showed low risk biasconclusionsthe prevalence chronic ankle instability shows wide range due different exclusion criteria age sports discipline factors among included studies future studies standardized criteria investigate epidemiology chronic ankle instability required epidemiology cai prospective factors affecting prevalence chronic ankle instability investigated clearly described,0.0
aggressive herpes zoster young patients multiple sclerosis dimethyl fumarate significance cd8 + natural killer cells neurol neuroimmunol neuroinflamm 2021 may 28 8 4 e1017 doi 101212 nxi0000000000001017 print 2021 julno abstractpmid34049996 doi101212 nxi0000000000001017,0.0
geneenvironment interactions multiple sclerosis uk biobank study neurol neuroimmunol neuroinflamm 2021 may 28 8 4 e1007 doi 101212 nxi0000000000001007 print 2021 julabstractobjective sought determine whether genetic risk modifies effect environmental risk factors multiple sclerosis ms test hypothesis tested statistical interaction polygenic risk scores prs capturing genetic susceptibility ms environmental risk factors ms uk biobankmethods people ms identified within uk biobank using icd10coded ms selfreport associations environmental risk factors ms risk quantified casecontrol design using multivariable logistic regression prs derived using clumpingandthresholding approach external weights largest genomewide association study ms separate scores created including major histocompatibility complex mhc prsmhc excluding prsnonmhc mhc locus bestperforming prs identified 30 cohort validated remaining 70 interaction environmental genetic risk factors quantified using attributable proportion due interaction ap multiplicative interactionresults data available 2 250 people ms 486 000 controls childhood obesity earlier age menarche smoking associated ms optimal prs strongly associated ms validation cohort prsmhc nagelkerkes pseudor2 0033 p 392 10111 prsnonmhc nagelkerkes pseudor2 0013 p 373 1043 strong evidence interaction polygenic risk ms childhood obesity prsmhc ap 017 95 ci 006025 p 0004 prsnonmhc ap 017 95 ci 006027 p 0006 conclusions study provides novel evidence interaction childhood obesity high burden autosomal genetic risk findings may significant implications understanding ms biology inform targeted prevention strategiespmid34049995 doi101212 nxi0000000000001007,0.0
antiganglioside antibodies celiac disease dear editor read great interest article cutillo et al analyzing multiple roles gangliosides key components sialic acids protection human microbial cells host immune response potential serve targets autoimmunity 1 discussion antiganglioside antibodies analysis various human pathologies antiganglioside antibodies reported authors mention celiac disease cd condition associated presence antigm1 antibodies also state triggering factor induces antiganglioside antibodies generation unknown however authors support hypothesis formation complexes gliadin gm1 ganglioside leads generation antibodies gm1 secondary product respect cd can considered autoimmune disease unusually several pathogenetic factors well known ie extrinsic trigger gliadin close genetic background hladq2 dq8 highly specific immune response directed wellcharacterized autoantigen tissue transglutaminase data presence antineuronal antibodies central enteric nervous systems provide support autoimmune hypothesis neurological dysfunction cd patients 2 3 4 previously described 2006 experience prevalence wider range antiganglioside antibodies clinical significance cd patients 5 6 using commercially available elisa kit immco diagnostics buffalo ny usa studied antigm1 antigd1b antigq1b serum igg igm antibodies 22 adult patients median age 35 range 1956 years three males 19 females cd neurological manifestations including eight cases idiopathic cerebellar ataxia seven cases epilepsy without cerebral calcifications two multiple sclerosis three attention memory impairment two peripheral neuropathiesin cases diagnosis cd confirmed endoscopic duodenal biopsy revealing different grades villous atrophy 3a 3c according modified marsh classification cd patients intestinal villous atrophy associated positivity serological cd markers antiendomysial antitissue transglutaminase antibodies supporting diagnosis cd available data regarding cd diagnosis diagnostic workup histopathology treatment obtained hospital digital databasein addition antiganglioside antibodies status assessed 30 patients cd without neurological dysfunction median age 37 years range 1759 years eight males 22 females 20 patients neurological disorders seven idiopathic cerebellar ataxia seven epilepsy four peripheral neuropathy one paraneoplastic syndrome subacute cerebellar atrophy one amyotrophic lateral sclerosis 50 patients immune system disorders six crohns disease four ulcerative colitis 10 autoimmune hepatitis 20 primary biliary cholangitis 10 calcifications raynauds phenomenon esophageal hypomotility sclerodactyly telangiectasia crest syndrome 20 blood donors comparable age sex demographics study approved local ethics committee patients controls gave informed consent beforeour antiganglioside antibodies assessment results summarized fig 1 least one three antiganglioside igg antibodies tested antigm1 antigd1b antigq1b found 64 cd patients neurological dysfunction compared 30 cd patients without neurological symptoms 50 neurological patients without cd 20 autoimmune controls none healthy controls p002 pns p0003 p00001 respectively fig 1figure1immunoglobulin g igg antibodies gm1 gd1b gq1b expressed percentage patients study population positive least one igg antibody cd neurological disorder vs cd without neurological disorder control group neurological disorder control group autoimmune disorder p002 pns p0003 respectively gm1 igg cd neurological disorder vs cd without neurological disorder control group neurological disorder control group autoimmune disorder p001 pns p002 respectively gd1b igg cd neurological disorder vs cd without neurological disorder control group neurological disorder control group autoimmune disorder p001 pns p002 respectively gq1b igg significant difference found fishers exact testfull size imageanalysis individual reactive antibody types showed antigm1 antigd1b igg significantly frequent cd patients neurological dysfunction cd patients without neurological symptoms autoimmune controls blood donors significant difference groups found antigq1b iggamong neurological patients cd six seven epilepsy two three attention deficit memory impairment syndrome three eight idiopathic cerebellar ataxia one two multiple sclerosis patients peripheral neuropathy antiganglioside igg antibodiesof 14 patients 11 showed reactivity one ganglioside two showed reactivity two gangliosides one patient showed reactivity three gangliosides within group neurological disorders without cd four seven idiopathic cerebellar ataxia four seven epilepsy two four peripheral neuropathy positive igg antibodies gangliosidesin patients autoimmune diseases antiganglioside antibodies found three six crohns disease one four uc two 10 aih two 20 pbc two 10 crest syndromeganglioside reactivity expressed terms enzymatic units aeu associated antigm1 antigd1b igg significantly higher cd patients neurological disorders antigm1 median 2035 aeu range 261365 au antigd1b median 165 aeu range 59794 aeu cd patients without neurological disorders antigm1 median 162 aeu range 59355 aeu antigd1b median 1205 aeu range 59331 aeu p004 p002 respectively autoimmune control patients antigm1 median 131 aeu range 53412 aeu antigd1b median 111 aeu range 59331 aeu p0007 p002 respectively healthy blood donors antigm1 median 125 aeu range 50240 antigd1b median 94 aeu range 11180 aeu p0009 p00001 respectively correlation found aeu antibodies gangliosides severity villous atrophy note 8 47 17 patients cd neurological manifestations positive least one antiganglioside igg antibody became negative antibody 1 year strict adherence glutenfree dietinterestingly antiganglioside igm antibodies although lower prevalence antiganglioside igg antibodies without significant difference among various groups studied confined three cases epilepsy within cd group neurological dysfunctioncd patients without neurological manifestations expected followup gluten free diet tested negative autoantibody markers cd exhibited autoantibodiesthe first description antiganglioside antibodies cd patients dates back 2002 alaidini et al reported positivity least one autoantibody directed gm1 gm2 gd1a gd1b gt1b gq1b gangliosides 6 cd patients peripheral neuropathy thus assuming neuropathy cd may autoimmune associated antiganglioside antibodies 7 2006 study authors confirmed presence antiganglioside antibodies celiac disease potential pathogenetic role autoimmune nonautoimmune neurological disorders table 1 table 1 prevalence antiganglioside antibodies celiac disease autoimmune nonautoimmune diseasesfull size tableinterestingly molecular mimicry microbial antigens lipooligosaccharides campylobacter jejuni gangliosides hypothesized possible mechanism antiganglioside antibodies generated thus reflecting abnormal immune response microbiota antigens 8 9 results detected antiganglioside antibodies beyond antigm1 confirm expand upon previously identified antineuronal antibodies eg hulike yolike detected indirect immunofluorescence patients cd neurological complications confirming hypothesis antiganglioside antibodies may result immunological disorder underlying cd 2 4 10 conclusion data support data described cutillo et al potential pathogenic role antiganglioside antibodies immunomediated neurological disorders provide evidence detection antiganglioside antibodies indicate associated neurological symptoms cd patients antiganglioside antibodies may therefore represent immunological markers neurological dysfunction cd patients included workup cd patients,0.0
retraction nutritional biochemical parameters among multiple sclerosis patients casecontrol study cureus 2021 may 27 13 5 r31 doi 107759 cureusr31abstract retracts article doi 107759 cureus15108 pmid34157058 pmcpmc8164918 doi107759 cureusr31,0.0
associations social network structure cognition amygdala volume multiple sclerosis exploratory investigation abstractbackgroundhumans inherently social biologically programmed connect others social connections known impact mental physical healthobjectivethe aim study test whether social network structure linked cognition mood fatigue regional brain volumes persons multiple sclerosis ms methodsa questionnaire quantifying individuallevel social network structure size density effective size constraint comprehensive battery neuropsychological tests magnetic resonance imaging mri administered 51 persons relapsingremitting ms linear regressions assessed associations network variables cognition depression fatigue structural brain volumesresultshigher network density constraint indicating stronger connections among network members associated worse language functions conversely larger network effective size measure nonredundant network members associated better language functions relationships network structure depression fatigue found larger network size related larger amygdala volumeconclusionfindings suggest social network structure linked language function amygdala volume persons ms patients closeknit networks showed worse language function open networks longitudinal studies larger samples warranted evaluate potential causal links social network structure msrelated cognitive impairment,0.0
scgrnom computational pipeline integrative multiomics analyses predicting celltype disease genes regulatory networks abstractunderstanding celltypespecific gene regulatory mechanisms genetic variants diseases remains challenging address developed computational pipeline scgrnom singlecell gene regulatory network prediction multiomics predict celltype disease genes regulatory networks including transcription factors regulatory elements applications schizophrenia alzheimers disease predicted disease genes regulatory networks excitatory inhibitory neurons microglia oligodendrocytes enrichment analyses revealed crossdisease diseasespecific functions pathways celltype level machine learning analysis also found celltype disease genes improved clinical phenotype predictions scgrnom generalpurpose tool available https githubcom daifengwanglab scgrnom,0.0
comparing medical cannabis use 5 us states retrospective database study background us states adopting medical cannabis laws since 1996 substantial variability medical cannabis programs states differences thoroughly investigated literature objective study compare medical cannabis patient characteristics across five states identify differences potentially caused differing policies surrounding condition eligibilitymethodswe conducted secondary analyses following retrospective study registry database data 33 medical cannabis evaluation clinics us owned operated cb2 insights study narrowed dataset include patients five states largest samples massachusetts n 27 892 colorado n 16 434 maine n 4591 connecticut n 2643 maryland n 2403 conduct indepth study characteristics patients accessing medical cannabis states including analysis variance compare average ages number conditions chisquared tests compare proportions patient characteristics statesresultsaverage ages varied states youngest average connecticut 422 oldest massachusetts 470 males represented approximately 60 patients data gender state majority patients state cannabis experience prior seeking medical certification primary medical conditions varied state chronic pain anxiety back neck problems topping list varying orders massachusetts maine maryland colorado 787 patients report chronic pain primary condition 704 patients connecticut reported posttraumatic stress disorder primary medical conditionconclusionthis study demonstrated significant impact policy patients access medical cannabis massachusetts colorado maine connecticut maryland utilizing realworld data highlights qualifications differ five states brings question routes patients states stricter regulations surrounding eligible conditions choose seek treatment cannabis patients may turn alternative treatments illicit recreational cannabis markets permitted,0.0
screening cognitive impairment patients multiple sclerosis crosssectional study georgia neurol res int 2021 may 27 20215591078 doi 101155 2021 5591078 ecollection 2021abstractcognitive impairment ci common symptom multiple sclerosis ms significant negative impact occupational social functioning patients study aimed estimate prevalence characteristics ci among ms patients georgia sixtyeight patients ms attending neurology outpatient clinic tbilisi georgia enrolled study cognitive status evaluated using two screening tools brief international cognitive assessment ms montreal cognitive assessment overall prevalence ci ms patients 47 found negative associations cognitive test results patients age disability status depression lower education higher scores expanded disability status scale progressive course ms main predictors ci logistic regression analysis first study georgia evaluate ci patients ms prevalence ci study comparable reported countries however found greater impairment executive system compared cognitive domains study patients continuous dmt showed significantly better performance cognitive tests used indicating possible favorable effect immunomodulatory drugs cognitionpmid34136283 pmcpmc8178012 doi101155 2021 5591078,0.0
m6a epitranscriptome neural development degeneration abstractn6methyladenosine m6a prevalent conserved abundant rna modification mrnas eukaryotes including mammals similar epigenetic dna modifications m6a proposed function critical regulator gene expression modification installed m6a methylation writers mettl3 mettl14 methyltransferase complex can reversed demethylase erasers fto alkbh5 furthermore m6a can recognized readers ythdf ythdc families may interpreted affect mrna splicing stability translation localization levels m6a methylation appear highest brain plays important functions embryonic stem cell differentiation brain development neurodevelopmental disorders depletion m6a methylation writer mettl14 mouse embryonic nervous systems prolongs cell cycle progression radial glia extends cortical neurogenesis postnatal stages recent studies imply dysregulated m6a methylation may significantly correlated neurodegenerative diseases review give overview m6a modifications neural development associated disorders provide perspectives studying m6a methylation,0.0
psychometric properties persian version paradise24 questionnaire int j prev med 2021 may 27 1250 doi 104103 ijpvmijpvm_300_19 ecollection 2021abstractbackground patients multiple sclerosis ms suffer wide range psychological problems application valid reliable tool psychosocial assessment required iranian patients aim study determine psychometric properties persian version paradise24 questionnaire iranian patients multiple sclerosismethods one hundred thirteen multiple sclerosis cases enrolled study participants asked answer valid reliable persian version fatigue severity scale social support scale pittsburg sleep quality index hospital anxiety depression scale translated version paradise24 questionnaire twenty cases filed questionnaire 2 weeks later assess reliability intraclass correlation coefficient cronbachs alpha correlation coefficients multiple regression analysis usedresults mean age mean duration disease 358 99 87 56 years respectively intraclass correlation coefficients ranged 08 094 cronbachs alpha values cronbachs alpha calculated 091 whole questionnaire also significant significant correlations paradise24 score expanded disability status scale r 042 p 0001 fatigue severity scale r 062 p 0001 anxiety r 043 p 0001 pittsburg sleep quality index scores r 046 p 0001 regression analysis considering paradise24 dependent variables independent showed expanded disability status scale fatigue severity scale anxiety score pittsburg sleep quality index positive predictors paradise24 scoreconclusions persian version paradise24 questionnaire valid reliable instrument evaluating psychosocial aspects patients multiple sclerosispmid34447492 pmcpmc8356966 doi104103 ijpvmijpvm_300_19,0.0
hsv1 endogenous retroviruses risk factors demyelination int j mol sci 2021 may 27 22 11 5738 doi 103390 ijms22115738abstractherpes simplex virus type 1 hsv1 neurotropic alphaherpesvirus can infect peripheral central nervous systems implicated demyelinating neurodegenerative processes transposable elements tes dna sequences can move one genomic location another tes linked several diseases affecting central nervous system cns including multiple sclerosis ms demyelinating disease unknown etiology influenced genetic environmental factors exogenous viral transactivators may activate certain retrotransposons class tes context several herpesviruses linked ms one hsv1 might act risk factor mediating processes molecular mimicry remyelination activity endogenous retroviruses ervs several herpesviruses involved regulation human ervs hervs hsv1 particular can modulate hervs cells involved ms pathogenesis review exposes current knowledge relationship hsv1 human ervs focusing contribution risk factor mspmid34072259 doi103390 ijms22115738,1.0
pseudotumoral demyelinating lesions presentation acute disseminated encephalomyelitis case rep neurol 2021 may 27 13 2 289296 doi 101159 000515174 ecollection 2021 mayaugabstractpseudotumoral forms demyelination related central nervous system demyelinating disorders usually considered atypical presentation multiple sclerosis including different varieties balos schilders marburg diseases lesions also seen myelin oligodendrocyte glycoprotein antibodyassociated demyelination acute disseminated encephalomyelitis adem neuromyelitis optica spectrum disorder pseudotumoral aspect may mistakenly considered abscess cancerous tumor case patients endure unnecessary possibly harmful brain biopsy delay disease diagnostics management latter differential diagnosis discarded pseudotumoral demyelination prompts uncertainties concerning nature underlying demyelinating condition prognosis management differ multiple sclerosis syndromes especially whether chronic treatment needed case report present 35yearold male patient hospitalized department neurology rapidly progressive onset encephalopathy polyfocal neurological deficits pseudotumoral lesions shown brain mri investigations adem likely diagnosis fit patients clinical radiological presentation thence put high dose intravenous corticosteroids followed good recovery within first week treatmentpmid34177535 pmcpmc8215961 doi101159 000515174,1.0
application creatine supplementation medical rehabilitation nutrients 2021 may 27 13 6 1825 doi 103390 nu13061825abstractnumerous health conditions affecting musculoskeletal cardiopulmonary nervous systems can result physical dysfunction impaired performance muscle weakness disuseinduced atrophy due welldocumented anabolic potential creatine monohydrate investigated supplemental agent mitigate loss muscle mass function variety acute chronic conditions review literature conducted assess current state knowledge regarding effects creatine supplementation rehabilitation immobilization injury neurodegenerative diseases cardiopulmonary disease muscular disorders several findings encouraging showcasing creatines potential efficacy supplemental agent via preservation muscle mass strength physical function however results consistent multiple diseases creatine studies small sample sizes published making difficult draw definitive conclusions rationale discordant findings complicated differences disease pathologies intervention protocols creatine dosing duration patient population creatine supplementation demonstrates promise therapeutic aid research needed fill gaps knowledge within medical rehabilitationpmid34071875 doi103390 nu13061825,0.0
impact covid19 home confinement neuromuscular performance functional capacity psychological state spanish people multiple sclerosis abstractbackgroundthe covid19 pandemic caused global confinement 2 months spain result general population significantly decreased physical activity levels consequences abrupt sedentary lifestyle spanish people multiple sclerosis pwms unknown aim examine impact covid19 home confinement neuromuscular performance functional capacity physical selfperception anxiety pwmsmethodseighteen pwms 810 men women age 43411088 years expanded disability status scale 285134 participated study rate force development rfd maximal voluntary isometric contraction knee extension legs timedup go test tug sittostand test 6min walk test 10m walk test physicalself perception questionnaire pspq statetrain anxiety inventory stai performed just home confinementresultsa nonsignificant moderate effect p007 es048 observed time sittostand test compared prehome confinement significant increase time tug p002 es067 psqp score decreased p001 es079 staistate increased p001 es065 following home confinementconclusionhome confinement impact functional capacity physical selfperception state anxiety however neuromuscular performance altered home confinement,1.0
reliability construct concurrent validity smartphonebased cognition test multiple sclerosis abstractbackgroundearly detection monitoring cognitive dysfunction multiple sclerosis ms may enabled smartphoneadapted tests allow frequent measurements everyday environmentobjectivesthe aim study determine reliability construct concurrent validity smartphoneadapted symbol digit modalities test ssdmt methodsduring 28day followup 102 patients ms 24 healthy controls hc used ms sherpa app perform ssdmt every 3 days smartphone patients performed brief international cognitive assessment ms baseline testretest reliability intraclass correlation coefficients icc construct validity group analyses cognitively impaired ci cognitively preserved cp hc differences concurrent validity correlation coefficients assessedresultspatients ms hc completed average 232 sd 100 183 sd 102 ssdmt respectively ssdmt demonstrated high testretest reliability iccs 08 smallest detectable change 7 points ssdmt scores different ci patients cp patients hc ps 005 ssdmt correlated modestly clinical sdmt highest r 0690 verbal highest r 0516 visuospatial memory highest r 0599 conclusionselfadministered smartphoneadapted sdmt scores reliable different patients ci cp hc demonstrated concurrent validity assessing information processing speed,0.0
impact covid19 multiple sclerosis topic discussion twitter stud health technol inform 2021 may 27 281865869 doi 103233 shti210302abstractintroduction multiple sclerosis ms one worlds common neurologic disorders social media proposed way maintain even increase social interaction people ms objective work identify compare topics twitter first wave covid19 pandemicmethods data collected using twitter api 9 2 2019 13 5 2020 sentistrength used analyze data day pandemic declared used turning point frequencyinverse document frequency tfidf used unigram calculated gains tfidf value comparative analysis relevance words categories among datasets performedresults original dataset contained 610k tweets final dataset 147 963 tweets 10th march categories gained relevance positive tweets healthcare professional chronic conditions condition burden negative tweets emotional aspects became relevant covid19 emerged new topicconclusions work provides insight covid19 changed online discourse people mspmid34042797 doi103233 shti210302,0.0
increased levels il16 central nervous system neuroinflammation associated infiltrating immune cells resident glial cells biology basel 2021 may 27 10 6 472 doi 103390 biology10060472abstractinterleukin il 16 cd4+ immune cell specific chemoattractant cytokine shown involved development multiple sclerosis inflammatory demyelinating disease central nervous system cns immune cells t cells macrophages reported producers il16 cellular source il16 cns less clear study investigates correlation il16 expression levels cns severity neuroinflammation determines phenotype cells produce il16 cns experimental autoimmune encephalomyelitis eae mice data show il16 expression significantly increased brain spinal cord tissues eae mice compared phosphate buffered saline pbs immunised controls dual immunofluorescence staining reveals significantly increased il16+ cells cns lesions eae mice likely cd45+ infiltrating immune cells cd4+ f4 80+ cells cns resident cd11b+ microglia gfap+ astrocytes neun+ neurons data suggest cytokine il16 closely involved eae pathology evidenced increased expression glial infiltrating immune cells impacts recruitment activation cd4+ immune cells neuroinflammationpmid34071825 doi103390 biology10060472,1.0
polyphenol saponinrich rhus tripartita extract apoptotic effect thp1 cells pi3k akt mtor signaling pathway background hyperactivation mechanistic target rapamycin mtor signaling pathway involved regulation cellular growth proliferation general common phenomenon types cancers thus natural substances targeting pathway can great therapeutic potential supporting treatment tumor patients rhus tripartita ucria grande plant growing desertic areas traditionally used treatment several diseases tunisia present work biochemical profile main compounds present plant leaf extract determined antileukemic potential plant extracts acute monocytic leukaemia aml thp1 cells investigatedmethodsafter hplc identification phenolic compounds present plant extract quantification saponin content cytotoxic effect rhus tripartita extracts thp1 cell culture evaluated using colorimetric mtt assay cell viability thp1 cells incubated medium containing relative ic50 concentrations total plant extract saponin extract standard compounds rutin r kaempferol k mixture catechin epicatechin epicatechingallate ceeg ellagic acid ea finally qrtpcr western blotting analysis used evaluate effect flavonoids present crude extract polyphenols total extract saponins cell survival apoptosisresultsanalysis expression level gene pik3ca pten akt1 mtor eif4e rps6kb1 tsc1 involved mtor pathway phosphorylation s6 akt proteins allowed observe total rhus tripartita extract compounds found extract controls thp1 cell proliferation apoptosis via regulation pi3kaktmtor signaling pathwayconclusionrhus tripartitainduced inhibition cell cycle induction apoptosis may involve mtor pathway therefore rhus tripartita extract may useful candidate natural anticancer drug support treatment aml,0.0
comparative efficacy intraoperative extracorporeal irradiated alcoholinactivated autograft reimplantation management osteosarcomasa multicentre retrospective study background biologic bone reconstruction limb salvage surgery treatment malignant bone tumours always controversial various inactivation methods convenience stability curative effects elicited associated costs need considered study aimed compare clinical efficacy intraoperative extracorporeal irradiated reimplantation alcoholinactivated autograft reimplantation limb salvage surgery patients osteosarcomamethodswe retrospectively analysed 28 patients osteosarcoma 14 patients treated intraoperative cobalt 60 irradiation reimplantation group 14 patients treated alcoholinactivated autograft reimplantation group b postoperative complications clinical efficacy treatment method compared statistical analysisresultsthe local recurrence rate 143 group complete bony union achieved 643 patients group 714 patients group b overall 5year survival rate 714 group 786 group b mean musculoskeletal tumor society msts score 2533 472 range 1530 group 2400 585 range 1530 group b mean international society limb salvage isols score 2579 513 range 2036 group 2614 533 range 2030 group b p 005 considered indicate significant difference results showed longterm clinical efficacy differ significantly two methodsconclusionsin limb salvage surgery osteosarcoma intraoperative extracorporeal irradiation alcoholinactivated autograft reimplantation yielded equivalent outcomes alcoholinactivated method may much convenient inexpensive way reconstruct bone defects additional studies well case studies needed fully evaluate clinical efficacy safety treatment method,0.0
histological ultrastructural degenerative findings gluteus medius tendon hip arthroplasty background despite gluteus medius gmed tendinosis relatively common presence association hip osteoarthritis oa total hip arthroplasty tha well studied hypothesized tendon degeneration found patients oa hip undergone tha control groupmethodsone hundred patients included 2016 2019 included 4 groups patients undergoing revision surgery two groups primary tha two groups 22 patients previously undergone primary tha direct lateral approach involving sectioning gmed tendon 24 patients previously undergone primary tha posterior approach leaving gmed tendon intact 29 patients primary hip oa 25 patients suffered femoral neck fracture served controls biopsies gmed tendon obtained time primary tha hip revision surgery tendon biopsies examined ultrastructurally histologicallyresultsultrastructurally direct lateral posterior revision groups statistically significantly collagen fibrils smaller diameters compared fracture primary tha groups moreover direct lateral revision group collagen fibrils smaller diameters compared posterior revision grouphistologically direct lateral revision group higher total degeneration score tds compared primary hip oa groupconclusionsthe gmed tendon shows ultrastructural degeneration patients undergo hip revision arthroplasty patients primary oa hip control patients suffered femoral neck fracture furthermore patients previously undergone primary tha direct lateral approach revealed histological gmed tendon degeneration patients suffer primary hip oa,0.0
inflammation possible trigger mitoxantroneinduced cardiotoxicity vivo study adult infant mice pharmaceuticals basel 2021 may 26 14 6 510 doi 103390 ph14060510abstractmitoxantrone mtx pharmaceutical drug used treatment several cancers refractory multiple sclerosis ms despite therapeutic value adverse effects may severe namely frequently reported cardiotoxicity whose mechanisms need research work aimed assess inflammation oxidative stressrelated pathways participate cardiotoxicity mtx using mouse animal model two different age periods infant adult mice using two therapeutic relevant cumulative doses histopathology findings showed mtx caused higher cardiac toxicity adults mtxtreated adults highest dose noradrenaline cardiac levels decreased whereas lowest cumulative dose protein carbonylation increased expression nuclear factor kappa b nfb p65 subunit m1 macrophage marker increased moreover mtxtreated adult mice enhanced expression nfb p52 tumour necrosis factor tnf decreasing interleukin6 il6 moreover catalase expression significantly increased adult infant mice treated lowest mtx cumulative dose expression glyceraldehyde3phosphate dehydrogenase gapdh glutathione peroxidase significantly increased infant animals nevertheless ratio gapdh atp synthase subunit beta decreased adult animals conclusion clinically relevant doses mtx caused dissimilar responses adult infant mice inflammation may important trigger mtxinduced cardiotoxicitypmid34073506 doi103390 ph14060510,0.0
role p2x7 receptors immune responses neurodegeneration front cell neurosci 2021 may 26 15662935 doi 103389 fncel2021662935 ecollection 2021abstractp2x7 receptors iongated channels activated atp pathological conditions extensive release atp induces sustained p2x7 receptor activation culminating induction proinflammatory pathways inflammasome assembly cytokine release inflammatory conditions whether occurring peripherally central nervous system cns increase bloodbrainbarrier bbb permeability besides wellknown involvement neurodegeneration neuroinflammation p2x7 receptor may induce bbb disruption chemotaxis peripheral immune cells cns resulting brain parenchyma infiltration instance despite common effects cytokine release p2x7 receptor signaling also associated metalloproteinase secretion activation well migration differentiation t lymphocytes monocytes dendritic cells highlight peripheral immune cells mediate pathogenesis multiple sclerosis parkinsons alzheimers disease mainly t lymphocyte neutrophil monocyte infiltration propose p2x7 receptor activation contributes neurodegenerative disease progression beyond known effects cns review discusses p2x7 receptor activation mediates responses peripheral immune cells within inflamed cns occurring aforementioned diseasespmid34122013 pmcpmc8187565 doi103389 fncel2021662935,0.0
tregresistant cytotoxic cd4+ t cells dictate t helper cells vicinity th17 skewing modulation proliferation int j mol sci 2021 may 26 22 11 5660 doi 103390 ijms22115660abstractcytotoxic cd4+ t cells cd4 ctl terminally differentiated t helper cells contribute autoimmune diseases multiple sclerosis developed novel triple coculture transwell assay study mutual interactions cd4 ctl conventional th cells regulatory t cells tregs simultaneously show cd4 ctl resistant suppression tregs vitro conditioned medium cd4 ctl accentuates suppressive phenotype tregs upregulating il10 granzyme b ctla4 pd1 demonstrate cd4 ctl conditioned medium skews memory th cells th17 phenotype suggesting cd4 ctl induce bystander polarization triple coculture assay cd4 ctl secretome promotes proliferation th cells even presence tregs however cellcell contact established cd4 ctl th cells proliferation th cells longer increased tregmediated suppression restored taken together results suggest th cells acquire cytotoxic properties tregresistant cd4 ctl affect proliferation phenotype conventional th cells vicinity creating proinflammatory microenvironment cd4 ctl may favor persistence expansion potentially pathogenic th cells thereby contributing pathogenic responses autoimmune disorderspmid34073458 doi103390 ijms22115660,0.0
elevated levels neutrophil gelatinaseassociated lipocalin among ocd patients exploratory study background obsessivecompulsive disorder ocd debilitating psychiatric disease characterized clinical heterogeneity complex pathophysiology complexity comes diversity pathophysiological factors proposed involved natural history disorder many theories ocd pathology support inflammation pathophysiological factor although studies consistent presence proinflammatory state among ocd patients however preclinical animal studies suggest lipocalin2 lcn2 analogous form acutephase proinflammatory protein neutrophil gelatinaseassociated lipocalin ngal may involved regulation stress response thought disrupted ocdmethodstwentyone ocd patients 19 healthy subjects participated exploratory study levels ngal assessed peripherous blood participants severity disease assessed using yalebrown obsessivecompulsive scale ybocs resultsocd patients exhibited significantly higher levels ngal compared healthy control subjects correlation found elevated levels ngal severity symptomsconclusionsthis first study report elevated levels ngal among ocd patients adding evidence possible role immune dysregulation pathophysiology ocd,0.0
mir20a suppresses treg differentiation targeting map3k9 experimental autoimmune encephalomyelitis background experimental autoimmune encephalomyelitis eae model inflammatory demyelinating diseases central nervous system cns group autoimmune diseases characterized inflammatory infiltration demyelination axonal damage mir20a dysregulated patients cns inflammatory demyelinating diseases however function mir20a remains unclear study intended explore role mir20a eaemethodsthe expression mir20a detected quantitative realtime pcr qrtpcr eae mice patients mog antibodyassociated demyelinating diseases cd4+ t cells eae mice sorted stimulated polarized mir20a knockdown activation differentiation cd4+ t cells analyzed flow cytometry expression target gene map3k9 detected qrtpcr western blot experiments binding mir20a 3 utr map3k9 tested luciferase assays feasibility mir20a therapeutic target alleviate severity eae explored intravenous administration mir20a antagomirs eae miceresultsmir20a upregulated splenocytes lymph node cells cd4+ t cells spinal cords eae mice moreover mir20a knockdown influence activation antigenspecific cd4+ t cells promoted differentiation treg cells map3k9 predicted target gene mir20a expressions map3k9 mir20a negatively correlated mir20a knockdown increased expression map3k9 addition mir20a binded 3 utr map3k9 simultaneous knockdown mir20a map3k9 counteracted enhanced differentiation tregs observed mir20a knocked alone furthermore injection mir20a antagomirs eae mice reduced severity disease increased proportion treg cells peripheral immune organsconclusionsmir20a suppresses differentiation antigenspecific cd4+ t cells tregs eae decreasing expression map3k9 mir20a antagomirs alleviate eae suggesting new therapy eae cns inflammatory demyelinating diseases,1.0
digital technology clinical trials multiple sclerosis systematic review j clin med 2021 may 26 10 11 2328 doi 103390 jcm10112328abstractclinical trials multiple sclerosis ms including digital technology tools overcome limitations treatment delivery disease monitoring march 2020 conducted systematic search pubmedgov clinicaltrialsgov databases restrictions identify relevant published unpublished clinical trials english language including ms patients digital technology applied used multiple sclerosis clinical trial main search words app digital electronic internet mobile additional search words separately digital technology part clinical trial interventions deliver psychotherapy motor rehabilitation exergames etraining robotassisted exercises digital technology used standardise previously existing outcome measures automatic acquisitions reduced inconsistencies improved detection symptoms eg electronic recording motor performance clinical trials using digital technology monitoring symptoms otherwise difficult detect eg fatigue balance measuring treatment adherence side effects selfassessment purposes collection outcome measures progressively shifting paperbased site internetbased site future internetbased home detection clinical treatment features remained otherwise invisible similarly remote interventions provide new possibilities motor cognitive rehabilitationpmid34073464 doi103390 jcm10112328,0.0
network analysis left anterior descending coronary arteries swimtrained rats situ video microscopic technique background aimed identify sex differences network properties recognize geometric alteration effects longterm swim training rat model exerciseinduced left ventricular lv hypertrophymethodsthirtyeight wistar rats divided four groups male sedentary female sedentary male exercised female exercised training sessions lv morphology function checked echocardiography geometry left coronary artery system analysed pressureperfused microsurgically prepared resistance artery networks using situ video microscopy segments 80 m diameter studied using divided 50mlong cylindrical ring units networks oxidativenitrative stress markers adenosine a2a estrogen receptor er investigated immunohistochemistryresultsthe lv mass index ejection fraction fractional shortening significantly increased exercised animals found substantial sex differences coronary network control groups swimtrained animals ring frequency spectra significantly different male female animals sedentary trained groups thickness wall higher males result training elevations populations 200 400m vessel units males thinner ones developed farther thicker ones closer orifice females new population 200 250m vessels appeared unusually close orificeconclusionsphysical activity lv hypertrophy accompanied remodelling coronary resistance artery network geometry different sexes,0.0
a2 b adenosine receptors sphingosine 1phosphate signaling crosstalk oligodendrogliogenesis front neurosci 2021 may 26 15677988 doi 103389 fnins2021677988 ecollection 2021abstractoligodendrocyteformed myelin sheaths allow fast synaptic transmission brain impairments process myelination demyelinating insults might cause chronic diseases multiple sclerosis ms physiological conditions remyelination ongoing process throughout adult life consisting differentiation oligodendrocyte progenitor cells opcs mature oligodendrocytes ols pathological events process fails due unfavorable environment adenosine sphingosine kinase sphingosine 1phosphate signaling axes sphk s1p play important roles remyelination processes remarkably fingolimod fty720 sphingosine analog recently approved ms treatment plays important roles opc maturation recently demonstrated selective stimulation a2 b adenosine receptors a2 b rs inhibit opc differentiation vitro reduce voltagedependent outward k+ currents k necessary opc maturation whereas specific sphk1 sphk2 inhibition exerts opposite effect opc differentiation a2 b r expression increases effect prevented sphk1 2 blockade furthermore selective silencing a2 b r opc cultures prompts maturation intriguingly enhances expression s1p lyase enzyme responsible irreversible s1p catabolism finally existence interplay sphk1 s1p pathway a2 b rs opcs confirmed since acute stimulation a2 b rs activates sphk1 increasing phosphorylation role a2 b r sphk s1p signaling oligodendrogenesis reviewed detail purpose shed new light interaction a2 b rs s1p signaling eventual innovative targets treatment demyelinating disorderspmid34135730 pmcpmc8202686 doi103389 fnins2021677988,1.0
temporal lobe epilepsy associated human herpes virus 6 abstracthuman herpes virus 6 hhv6 ubiquitous common pathogen affects humans human herpes virus 6b hhv6b wide spread human herpesvirus infects people children establishes latent infections central nervous system cns especially hippocampus amygdala induces neurologic diseases hhv6 can establish latent infection reactivated various stimuli recently viral genomic dna hhv6b detected surgically removed brain tissues intractable epilepsy patients suggesting involvement hhv6b pathogenesis epilepsy temporal lobe epilepsy tle shown closely related hhv6b tle patients hhv6b brains suffer reiterative attacks febrile seizures hippocampal sclerosis however mechanisms underlying contribution virus development tle remains unknown direct damage immune activation caused virus involved process neuron damage abnormal neural circuit formation glial cell proliferation addition cytokines like interleukin17a il17a nuclear factorkappa b nfb transforming growth factor tgf mitogenactivated protein kinase mapk phospholipase a2 upregulated involved pathological process tle studies needed clarify mechanisms underlying link hhv6b epilepsy identify biomarkers recognize different patient groups antiinflammatory immunomodulatory therapies,0.0
assessment central retinal thickness choroidal thickness retinal nerve fiber layer psoriasis spectraldomain optical coherence tomography study background study aims evaluate choroidal thickness ct retinal thickness ganglion cellinner plexiform layer gcipl retinal nerve fiber layer rnfl structures psoriasis patients using optical coherence tomography oct methodsthis study included 33 psoriasis patients 33 healthy individuals moreover psoriasis patients use systemic antiinflammatory treatment evaluated retinal choroidal images participants obtained spectraldomain oct furthermore ct measured subfoveal temporal nasal positions 500m intervals distance 1 500 m foveal centerresultsthe mean psoriasis area severity index pasi score 570 range 240900 significant differences found subfoveal p 0659 temporal nasal ct values psoriasis patients compared control group p 005 similarly statistically significant differences found groups terms central retinal thickness macular gcipl rnfl p 005 moreover significant correlation exists duration psoriasis disease pasi scores oct parameters p 005 conclusionsno significant changes ct ganglion cell layer rnfl retinal thickness values noted psoriasis patients mild moderate mean pasi score,0.0
cpgmotifs tool discover dna motifs associated cpg methylation events background investigation molecular alterations associated conservation variation dna methylation eukaryotes gaining interest biomedical research community among different determinants methylation stability dna composition cpg surrounding regions shown crucial role maintenance establishment methylation statuses aspect previously characterized quantitative manner inspecting nucleotidic composition region research field still lacks qualitative perspective linked identification certain sequences dna motifs related particular dna methylation phenomenaresultshere present novel computational strategy based short dna motif discovery order characterize sequence patterns related aberrant cpg methylation events provide framework userfriendly shinybased application cpgmotifs easily retrieve characterize dna patterns related cpg methylation human genome tool supports functional interpretation deregulated methylation events predicting transcription factors binding sites tfbs encompassing identified motifsconclusionscpgmotifs open source software source code available github https githubcom grecolab cpgmotifs readytouse docker image provided dockerhub https hubdockercom r grecolab cpgmotifs,1.0
treatmentinduced baff expression b cell biology multiple sclerosis front immunol 2021 may 26 12676619 doi 103389 fimmu2021676619 ecollection 2021abstractalthough fingolimod interferon two mechanistically different multiple sclerosis ms treatments induce b cell activating factor baff shift b cell pool towards regulatory phenotype however whether shared mechanism treatments influence b cell compartment remains elusive study collected crosssectional study population 112 ms patients 41 untreated 42 interferon 29 fingolimod determined b cell subsets cellsurface rna expression baffreceptor baffr transmembrane activator cyclophilin ligand interactor taci well plasma rna levels baff baff splice forms interleukin10 il10 35 il35 added vitro b cell culture four stimulus conditions medium cpg baff cpg+baff untreated interferon treated patients including measurement intracellular il10 levels flow experiments showed interferon fingolimod induced baff protein mrna expression p 315 x 104 without disproportional change antagonizing splice form protein baff correlated increase transitional b cells p 570 x 106 decrease switched b cells p 329 x 104 reduction b cellsurface baffr expression p 270 x 1010 tacipositive negative cells taci baffr rna levels remained unaltered rna plasma vitro experiments demonstrated baff associated increased il10 il35 levels conclusion treatmentinduced baff correlates shift towards transitional b cells enriched cells immunoregulatory function however baff directly influence expression immunoregulatory cytokines il10 il35 furthermore posttranslational mechanism baffinduced baffr cell surface loss taciindependent observations put failure pharmaceutical antibaff strategies perspective provide insights targeted b cell therapiespmid34122439 pmcpmc8187869 doi103389 fimmu2021676619,0.0
demyelination remyelination detected alternative cuprizone mouse model multiple sclerosis 70 t multiparameter magnetic resonance imaging sci rep 2021 may 26 11 1 11060 doi 101038 s41598021905976abstractthe aim study investigate mechanisms underlying demyelination remyelination 70 t multiparameter magnetic resonance imaging mri alternative cuprizone cpz mouse model multiple sclerosis ms sixty mice divided six groups n 10 groups imaged 70 t multiparameter mri treated alternative cpz administration schedule t2weighted imaging t2wi susceptibilityweighted imaging swi diffusion tensor imaging dti used compare splenium corpus callosum scc among groups prussian blue luxol fast blue staining performed assess pathology correlations mean grayscale value mgsv pathology results mri metrics analyzed evaluate multiparameter mri results oneway anova post hoc comparison showed normalized t2wi t2nor fractional anisotropy fa mean diffusivity md radial diffusivity rd axial diffusivity ad values significantly different among six groups mean phase value swi significantly different among groups correlation analysis showed correlation t2nor mgsv higher among values correlations among fa rd md mgsv remained instructive conclusion ultrahighfield multiparameter mri can reflect pathological changes associated underlying mechanisms demyelination remyelination ms successful establishment acute cpzinduced modelpmid34040141 doi101038 s41598021905976,1.0
assessing migraine patients multifocal pupillographic objective perimetry background establish effects stimulating intrinsicallyphotosensitive retinal ganglion cells iprgcs migraine severity determine migraine produces objectivelymeasured visual field defectsmethodsa randomized open labelled crossover study tested migraineurs normal controls using multifocal pupillographic objective perimetry mfpop 44 testregions eye slow blue protocol bp stimulated iprgcs fast yellow protocol yp stimulated luminance channels migraine diaries assessed migraine severity perregion responses analyzed according response amplitude timetopeakresultsthirtyeight migraineurs 420 165 years 23 females 24 normal controls 392 152 years 14 females tested proportion subjects developing migraine differ either protocol either 1st day odds ratio 10 95 confidence interval 0244 p 048 first 3 days testing odds ratio 08 95 confidence interval 0321 p 068 migraine days week increase following testing either protocol comparison baseline week 14 16 pretesting mean sd 13 14 postbp 13 12 postyp p 096 neither measures severity migraine occurring 2 weeks testing significantly lowered amplitudes 064 014 db mean se triptan use increased amplitudes 045 010 db p 0001conclusionsstimulating iprgcs affect migraine occurrence severity pupillary response characteristics influenced occurrence recent migraine attack history triptan use,0.0
tolllike receptor homolog cd180 expression diminished natural autoantibodyproducing b cells patients autoimmune cns disorders j immunol res 2021 may 25 20219953317 doi 101155 2021 9953317 ecollection 2021abstractpurpose decreased expression tlr homolog cd180 peripheral blood b cells potential role antibody production described autoimmune diseases effectiveness anticd20 therapy neuromyelitis optica spectrum disorder nmosd multiple sclerosis ms strengthens role b cells pathogenesis therefore aimed investigate cd180 expression peripheral blood b cell subsets nmosd ms patients analyze levels natural anticitrate synthase cs igg autoantibodies igg antibodies induced bacterial infections reported play role pathogenesis nmosd msmethods analyzed distribution cd180 expression peripheral blood b cell subsets defined cd19 cd27 igd staining measured antics igm g natural autoantibody antibacterial igg serum levels nmosd rrms healthy controls hc results found decreased nave increased memory b cells nmosd compared ms among investigated four b cell subsets cd180 expression exclusively decreased cd19+cd27+igd+ nonswitched ns memory b cells nmosd ms compared hc furthermore antics igm natural autoantibody serum level lower nmosd ms addition found tendency higher antics igg natural autoantibody levels antichlamydia igg antibodypositive nmosd ms patientsconclusions results suggest reduced cd180 expression ns b cells contribute deficient natural igm autoantibody production nmosd ms whereas natural igg autoantibody levels show association antibacterial antibodiespmid34124274 pmcpmc8169253 doi101155 2021 9953317,0.0
serum neurofilament levels reflect outer retinal layer changes multiple sclerosis ther adv neurol disord 2021 may 25 1417562864211003478 doi 101177 17562864211003478 ecollection 2021abstractbackground serum neurofilament light chain snfl distinct intraretinal layers promising biomarkers neuroaxonal injury multiple sclerosis ms aimed unravel association markers early ms identified neurofilament distinct immunohistochemical expression pattern among intraretinal layersmethods threedimensional 3d spectral domain macular optical coherence tomography scans snfl levels investigated 156 early ms patients female male 109 47 mean age 333 95 years mean disease duration 20 33 years whole cohort 110 patients history optic neuritis nhon 46 patients previous history optic neuritis hon addition subgroup patients n 38 studied longitudinally 2 years support vector machine analysis applied test regression model significant changesresults cohort hon patients thinner outer plexiform layer opl volume compared nhon patients b 0016 se 0006 p 0013 higher snfl levels significantly associated thinner opl volumes hon patients b 6734 se 2514 p 0011 finding corroborated longitudinal subanalysis association higher snfl levels opl atrophy b 5974 se 2420 p 0019 snfl levels 757 accurate predicting opl volume supervised machine learningconclusions summary snfl levels good predictor future outer retinal thinning ms changes within neurofilamentrich opl considered additional retinal marker linked ms neurodegenerationpmid34104217 pmcpmc8155762 doi101177 17562864211003478,0.0
structured reporting brain mri following mechanical thrombectomy acute ischemic stroke patients background compare quality freetext reports ftr structured reports sr brain magnetic resonance imaging mri examinations patients following mechanical thrombectomy acute stroke treatmentmethodsa template sr brain mri examinations based decision trees designed developed house applied twenty patients acute ischemic stroke addition ftr two experienced stroke neurologists independently evaluated quality ftr sr regarding clarity content presence key features information extraction overall report quality statistical analysis differences ftr sr performed using mannwhitney utest chisquared test resultsclarity p 0001 comprehensibility p 0001 inclusion relevant findings p 0016 structure p 0005 satisfaction content report immediate patient management p 0001 evaluated significantly superior sr neurologist raters one rater additionally found explanation patients clinical symptoms p 0003 completeness p 0009 length p 0001 sr significantly superior compared ftr stated remained open questions requiring consultation radiologist p 0001 neurologists preferred sr ftrconclusionsthe use sr brain magnetic resonance imaging may increase report quality satisfaction referring physicians acute ischemic stroke patients following mechanical thrombectomytrial registration retrospectively registered,0.0
update neurological short tandem repeat expansion disorders emergence longread sequencing diagnostics background short tandem repeat str expansion disorders important cause human neurological disease established role 40 different phenotypes including myotonic dystrophies fragile x syndrome huntingtons disease hereditary cerebellar ataxias amyotrophic lateral sclerosis frontotemporal dementiamain bodystr expansions difficult detect may explain unsolved diseases highlighted recent findings including discovery biallelic intronic aaggg repeat rfc1 cause cerebellar ataxia neuropathy vestibular areflexia syndrome canvas finding cgg repeat expansions notch2nlc cause neuronal intranuclear inclusion disease range clinical phenotypes however established laboratory techniques diagnosis repeat expansions repeatprimed pcr southern blot cumbersome lowthroughput poorly suited parallel analysis multiple gene regions next generation sequencing ngs increasingly used established shortread ngs platforms eg illumina unable genotype large complex repeat expansions longread sequencing platforms recently developed oxford nanopore technology pacific biosciences promise overcome limitations deliver enhanced diagnosis repeat expansion disorders rapid costeffective fashionconclusionwe anticipate longread sequencing will rapidly transform detection short tandem repeat expansion disorders clinical diagnosis gene discovery,0.0
measuring impact covid19 quality life survivors partners family members crosssectional international online survey bmj open 2021 may 25 11 5 e047680 doi 101136 bmjopen2020047680abstractobjective study aimed measure impact covid19 quality life qol survivors partners family membersdesign setting prospective crosssectional global online survey using social mediaparticipants patients covid19 partners family members age 18 years intervention online survey june august 2020main outcome measure euroqol group five dimensions three level eq5d3l measure qol survivors covid19 family reported outcome measure from16 assess impact partner family members qolresults survey completed 735 covid19 survivors mean age48 years females563 mean 128 weeks diagnosis 571 partners 164 family members n735 mean age47 years females246 europe 506 north america 385 rest world 109 eq5d mean score covid19 survivors 865 sd19 median9 range614 811 596 735 reported pain discomfort 795 584 735 problems usual activities 687 505 735 anxiety depression 562 413 735 problems mobility hospitalised survivors 201 n148 survivors existing health conditions 309 n227 reported significantly problems mobility usual activities p005 hospitalised also experiencing impact selfcare p0001 among 735 partners family members mean from16 score maximum scorehighest impact 32 15 median15 range032 936 688 735 reported worried 817 601 735 frustrated 784 676 735 sad 833 612 735 reported impact family activities 689 507 735 sleep 681 500 735 sex lifeconclusion covid19 survivors reported major persisting impact physical psychosocial health lives partners family members also severely affected need holistic support system sensitive needs covid19 survivors family members experience major secondary burdenpmid34035105 doi101136 bmjopen2020047680,0.0
new therapeutic approaches mesenchymal stem cellsderived exosomes abstractmesenchymal stem cells mscs demonstrated great potential treatment several diseases due differentiation immunomodulatory capabilities ability easily cultured manipulated recent investigations revealed therapeutic effect largely mediated secretion paracrine factors including exosomes exosomes reflect biophysical features mscs considered effective mscs alternative approaches based mscderived exosomes can offer appreciable promise overcoming limitations practical challenges observed cellbased therapy furthermore mscderived exosomes may provide potent therapeutic strategy various diseases promising candidates cellbased cellfree regenerative medicine review briefly summarizes development mscs treatment human diseases well describes current knowledge exosomes biogenesis molecular composition exert effects target cells particularly therapeutic potential mscderived exosomes experimental models recent clinical trials evaluate safety efficacy summarized study overall paper provides current overview exosomes new cellfree therapeutic agent,0.0
kynurenines neurofilament light chain multiple sclerosis front neurosci 2021 may 25 15658202 doi 103389 fnins2021658202 ecollection 2021abstractmultiple sclerosis autoimmune demyelinating neurodegenerative disease central nervous system recent years proven kynurenine system plays significant role development several nervous system disorders including multiple sclerosis kynurenine pathway metabolites neurotoxic neuroprotective effects moreover enzymes kynurenine pathway play important role immunomodulation processes among others well interacting neuronal energy balance various redox reactions dysregulation many enzymatic steps kynurenine pathway upregulated levels metabolites locally central nervous system contribute progression multiple sclerosis pathology process can initiate pathogenic cascade including microglia activation glutamate excitotoxicity chronic oxidative stress accumulated mitochondrial damage axons finally disrupt homeostasis neurons leads destabilization neuronal cell cytoskeleton contributes neuroaxonal damage neurodegeneration neurofilaments good biomarkers neuroaxonal damage level reliably indicates severity multiple sclerosis treatment response increasing evidence connections exist molecules generated kynurenine metabolic pathway change neurofilament concentrations thus alterations kynurenine pathway may important biomarker course multiple sclerosis present review report possible relationship connection neurofilaments kynurenine system multiple sclerosis based available evidencespmid34113231 pmcpmc8185147 doi103389 fnins2021658202,1.0
childhood pet ownership multiple sclerosis systematic review metaanalysis abstractbackgroundmany studies conducted investigating range environmental factors implicated pathogenesis multiple sclerosis ms collated available data exposure domestic animals symptom onset ms perform systematic review metaanalysismethodsmedline embase cinahl searched relevant articles based predefined inclusion exclusion criteria reference lists handsearched data extracted critical analysis conducted using newcastleottawa criteria metaanalysis used random effectsresultsstudy heterogeneity high study quality variable random effects metaanalysis showed associations pet ownership development msconclusionit possible draw definitive conclusions work studies included high level heterogeneity many variables involved pet ownership exposure nature way studied makes analysis challenging,0.0
altered immune phenotypes hladqb1 gene variation multiple sclerosis patients failing interferon beta treatment front immunol 2021 may 25 12628375 doi 103389 fimmu2021628375 ecollection 2021abstractbackground interferon beta ifn prescribed firstline diseasemodifying therapy relapsingremitting multiple sclerosis rrms nearly three decades however still lack treatment response markers correlate clinical outcome patientsaim determine combination cellular molecular blood signatures associated efficacy ifn treatment using integrated approachmethods immune status 40 rrms patients 15 untreated 25 received ifn1a treatment 15 responders 10 nonresponders investigated phenotyping regulatory cd4+ t cells nave memory t cell subsets measurement circulating ifn proteins digital elisa simoa analysis 600 immune related genes including 159 interferonstimulated genes isgs nanostring technology potential impact hla class ii gene variation treatment responsiveness investigated genotyping hladrb1 drb3 4 5 dqa1 dqb1 using control population milieu interieur cohort 1 000 french healthy donorsresults clinical responders nonresponders displayed similar plasma levels ifn similar isg profiles however nonresponders mainly differed subject groups reduced circulating nave regulatory t cells enhanced terminally differentiated effector memory cd4+ temra cells altered expression least six genes immunoregulatory function moreover nonresponders enriched hladqb1 genotypes encoding dq8 dq2 serotypes interestingly two serotypes associated type 1 diabetes celiac disease overall immune signatures nonresponders suggest active disease resistant therapeutic ifn cd4+ t cells likely restricted dq8 dq2 exert enhanced autoreactive bystander inflammatory activitiespmid34113337 pmcpmc8185344 doi103389 fimmu2021628375,0.0
high resolution haplotype analyses classical hla genes families multiple sclerosis highlights role hladp alleles disease susceptibility front immunol 2021 may 25 12644838 doi 103389 fimmu2021644838 ecollection 2021abstractmultiple sclerosis ms susceptibility shows strong genetic associations hla alleles haplotypes genotyped 11 hla genes 477 nonhispanic european ms patients 954 unaffected parents using validated nextgeneration sequencing ngs methodology hla haplotypes assigned unequivocally tracing hla allele transmissions explored hla haplotype allele associations ms using genotypic transmission disequilibrium test gtdt multiallelic tdt mtdt also conducted casecontrol cc study patients 2029 healthy unrelated ethnically matched controls performed separate analyses 54 extended multicase families reviewing transmission haplotype blocks haplotype fragment including drb5010101drb115010101 significantly associated predisposition gtdt p 220e16 mtdt p 161e07 cc p 222e16 reported previously second risk allele dpb110401 gtdt p 369e03 mtdt p 299e03 cc p 100e02 independent haplotype bearing drb11501 newly identified allele drb1010101 showed significant protection gtdt p 868e06 mtdt p 450e03 cc p 196e06 two dqb1 alleles dqb10301 gtdt p 286e03 mtdt p 556e02 cc p 408e05 dqb10303 gtdt p 117e02 mtdt p 116e02 cc p 121e02 defined twofield level also showed protective effects hla class block a02010101c03040101b400102 gtdt p 586e03 mtdt p 365e02 cc p 969e03 alleles b2705 gtdt p 628e04 mtdt p 215e03 cc p 147e02 b3801 gtdt p 320e03 mtdt p 614e03 cc p 170e02 showed moderately protective effects independently class ii associated factors comparing statistical significance 11 hla loci 19 haplotype segments untruncated twofield allele names precisely mapped ms candidate alleles haplotypes eliminating false signals resulting hitchhiking alleles assessed genetic burden hla allele haplotype identified study familybased study including highestresolution hla alleles proved powerful efficient precise identification hla genotypes associated susceptibility protection development mspmid34211458 pmcpmc8240666 doi103389 fimmu2021644838,0.0
effect australian bushfires covid19 pandemic health behaviours people multiple sclerosis abstractbackgroundcrises disasters disproportionally impact people chronic health conditions multiple sclerosis ms objectiveto assess impact covid19 pandemic australian black summer bushfires health behaviours people msmethodspeople ms carers healthcare advocacy professionals recruited online mayjuly 2020 online survey telephone interviewsresultssurvey items relating health behaviours completed 113 people ms 18 people ms 4 ms advocates 5 healthcare professionals 2 carers interviewed bushfires affected 345 pandemic affected 743 survey participants ms pandemic bushfires caused decrease physical activity 538 553 participants respectively well increases unhealthy eating 436 243 respectively alcohol consumption 354 105 respectively decrease typical sleeping patterns 405 395 respectively conversely 275 participants reported increase physical activity pandemic interview data detailed circumstances motivations changes health behaviours well consequences including reduced mobility fitness mood disturbances weight gainconclusionthere need increase support health promotion people ms maintain initiate positive health behaviours especially times adversity,0.0
attitudes toward vaccination patients multiple sclerosis report iran recent pandemic novel coronavirus sars cov2 brought many psychosocial changes among different societies worldwide patients chronic diseases especially immunemodulatory immune suppressor drugs need special attention multiple sclerosis ms chronic autoimmune disease central nervous system globally estimated affect 28 million people walton et al 2020 iran one areas significant prevalence ms 293 100 000 azami et al 2019 facing difficult time high incidence mortality rate covid19 country https wwwworldometersinfo coronavirus country iran 2021 raised concerns among ms patients rezaeimanesh et al 2020 higher rates depression interruptions psychological supports changes lifestyles cognitive issues differences coping strategies may add disease burden group costabile et al 2020 fortunately besides following precautions vaccination brought hope people every corner world studied ms patients attitudes toward vaccination effect disease,0.0
discovery bms753426 potent orally bioavailable antagonist cc chemokine receptor 2 acs med chem lett 2021 may 25 12 6 969975 doi 101021 acsmedchemlett1c00082 ecollection 2021 jun 10abstractto improve metabolic stability profile bms741672 1a undertook structureactivity relationship study trisubstituted cyclohexylamine series ultimately led identification 2d bms753426 potent orally bioavailable antagonist ccr2 compared previous clinical candidate 1a tertbutyl amine 2d showed significant improvements pharmacokinetic properties lower clearance higher oral bioavailability furthermore compound 2d exhibited improved affinity ccr5 good activity models monocyte migration multiple sclerosis hccr2 knockin mouse synthesis 2d facilitated development simplified approach key intermediate 4r 9b deployed stereoselective reductive amination may prove general interestpmid34141082 pmcpmc8201760 doi101021 acsmedchemlett1c00082,0.0
effect average temperature suicide rates five urban california counties 19992019 ecological time series analysis background suicide among top 10 leading causes premature morality united states rates continue increase thus prevention become salient public health responsibility risk factors suicide transcend individual societal level risk can increase based climatic variables purpose present study evaluate association average temperature suicide rates five populous counties california using mortality data 1999 2019methodsmonthly counts death suicide five counties interest obtained cdc wonder monthly average maximum minimum temperature obtained nclimdiv time period modelled association temperature variable suicide rate using negative binomial generalized additive models accounting countyspecific annual trend monthly seasonalityresultsthere 38 000 deaths suicide californias five populous counties 1999 2019 increase average temperature 1 c corresponded 082 increase suicide rate irr 10082 per c 95 ci 1002510140 estimated coefficients maximum temperature irr 10069 per c 95 ci 1002110117 minimum temperature irr 10088 per c 95 ci 1002310153 similarconclusionthis study adds growing body evidence supporting causal effect elevated temperature suicide investigation environmental causes suicide well biological societal contexts mediating relationships critical development implementation new public health interventions reduce incidence suicide particularly face increasing temperatures due climate change,0.0
multiple sclerosis drug discovery work translation abstractmultiple sclerosis ms trauma important neurological disease young adults affecting 1 per 1000 individuals currently available medications targeting immune system satisfactory results obtained patients relapsing ms can serious adverse effects moreover despite promising developments b cell targeting therapies sphingosine1phosphate modulating drugs still high unmet need safe drugs broad efficacy patients progressive ms despite substantial investments intensive preclinical research proportion promising lead compounds reaches approved drug status remains disappointingly low one cause lies poor predictive validity ms animal models used translation pathogenic mechanisms safe effective treatments patient disturbing situation raised criticism relevance animal models used preclinical research calls improvement models publication presents potentially useful strategy enhance predictive validity ms animal models namely analyze causes failure forward translation lab clinic via reverse translation clinic lab strategy new insights can gained can help generate valid ms models,0.0
mait cells microbiota multiple sclerosis autoimmune diseases microorganisms 2021 may 24 9 6 1132 doi 103390 microorganisms9061132abstractthe functions mucosalassociated invariant t mait cells homeostatic conditions include interaction microbiota products protection body barriers mounting tissuerepair response injuries infections dysfunction mait cells dysbiosis occur common chronic diseases inflammatory metabolic tumor nature review aimed analyzing changes mait cells well microbiota multiple sclerosis autoimmune disorders common features dysbiosis conditions reduced richness microbial species unbalance proinflammatory immune regulatory components gut microbiota literature concerning mait cells disorders rather complex sometimes consistent multiple sclerosis autoimmune conditions several studies done progress find correlations intestinal permeability dysbiosis mait cell responses clinical biomarkers treated treatmentnave patients final aims explain activates mait cells diseases primarily infective interactions microbiota potentially pathogenic dynamics related disease course diseasemodifying treatmentspmid34074025 doi103390 microorganisms9061132,0.0
impact air pollution moderate severe relapses among multiple sclerosis patients abstractbackgroundmultiple sclerosis ms chronic inflammatory disease central nervous system genetic environmental componentobjectivein current study examined association incidence ms moderate severe relapses exposure air pollutants meteorological exposuresmethodswe enrolled ms patients southern israel 20002017 exposure assessment relied satellitebased model exposure particulate matter size 25 10 microns pm25 pm10 temperature spatial resolution 1 km kloogetal 2015 information exposure nitrogen dioxide no2 sulfur dioxide so2 ozone o3 levels completed database monitoring stations analyzed data using semiecological approach monthly incidence msrelated relapses requiring hospitalization function environmental factors analyzed timeseries technique adjusting sex age smoking also used casecrossover approach compare environmental exposure patient day relapse exposure relapsefree days estimates adjusted heat index divided iqrresultsthere 287 ms patients study average age 528 167 years 37 107 40 mostly female 662 136 patients smoking 47 nonsmoking 394 unknown pm25 independently associated ms relapses within nonsmoking population relative risk rr 128 95ci101162 o3 found adversely associated ms relapses among patients younger 40 rr158 95ci 103443 based casecrossover approach relapses associated elevated levels pm10 no2 subjects odds ratio 105 95ci100111 or185 95ci 128268 respectively adverse association pm25 observed nonsmokers 112 95ci 100125 conclusionsthe findings show ms relapses adversely associated ambient exposure pm no2,0.0
earlyonset alcohol dependence multiple sclerosis diagnostic challenges int j environ res public health 2021 may 24 18 11 5588 doi 103390 ijerph18115588abstractmultiple sclerosis ms inflammatory demyelinating disorder characterized progressive disruption myelin sheath around nerve fibres early initiation diseasemodifying treatments crucial preventing disease progression neurological damage unfortunately diagnostic delay several years uncommon particularly presence physical mental comorbidities among psychiatric comorbidities role alcohol misuse still debate paper discuss case earlyonset alcohol dependence possible role delaying initiation specific therapy ms differential diagnosis idiopathic secondary neurodegenerative disorders often challenging dealing patients reporting earlyonset substance abuse likely present organic damage clinicians may prone formulate diagnosis secondary neuropathy particularly facing nonspecific symptoms case report highlights need indepth medical investigations including imaging presence neurological signs suggesting damage central nervous system prompting differential diagnosis idiopathic secondary neurodegenerative conditions indeed timely diagnosis crucial initiation specific therapies positively affecting outcomepmid34073738 doi103390 ijerph18115588,1.0
tracing neurological diseases presymptomatic phase insights neurofilament light chain front neurosci 2021 may 24 15672954 doi 103389 fnins2021672954 ecollection 2021abstractthe identification neurological diseases presymptomatic phase will fundamental aim coming years step necessary optimize early diagnostics verify effectiveness experimental disease modifying drugs early stages diseases among biomarkers can detect neurological diseases already preclinical phase neurofilament light chain nfl given promising results recently measurement serum enabled identification neurodegeneration diseases multiple sclerosis ms alzheimers disease ad 610 years onset symptoms similar results obtained conditions frontotemporal dementia ftd amyotrophic lateral sclerosis als 2 years clinical onset study longitudinal dynamics serum nfl also revealed interesting aspects pathophysiology diseases preclinical phase review sought discuss recent findings serum nfl presymptomatic phase neurological diseasespmid34108859 pmcpmc8180886 doi103389 fnins2021672954,0.0
subcutaneous interferon beta therapy multiple sclerosis patients characterization injection site reactions flulike symptoms daily practice setting results noninterventional study perfect patient prefer adherence 2021 may 24 1510911100 doi 102147 ppas307987 ecollection 2021abstractpurpose purpose study assess prevalence injection site reactions isr flulike symptoms fls treatment subcutaneous sc interferon ifn beta therapies document measures mitigate prevent isr flspatients methods crosssectional postauthorization safety study perfect conducted 11 2017 7 2019 neurology practices germany adult patients relapsingremitting multiple sclerosis ms receiving sc ifn beta 3 months eligible primary endpoints patientreported prevalence isr fls additional endpoints reported patients ms nurses neurologists included type frequency duration time occurrence management isr flsresults total 603 patients median age 45 years range 3653 74 female included analysis time since ms diagnosis 5 years patients majority received none 64 1 22 prior therapy current ms therapy 36 32 30 patients ifn beta1b ifn beta1a peginterferon beta1a respectively isr fls current therapy reported 84 68 patients respectively isr developed within 5 days injection 84 lasted 214 days 53 patients frequent patientreported symptom erythema 39 isr resolved abated systemic treatments topical ointments frequent preventive measures included alternating injection sites 58 occurrence isr rarely resulted treatment interruption 5 fls occurred predominantly 6 h injection 40 lasted 12 h 26 frequent patientreported symptoms fatigue 15 aching limbs 15 assessments physicians ms nurses differed patientreported resultsconclusion although isr experienced majority patients rarely resulted treatment interruption realworld setting isr fls management line published expert recommendationspmid34079229 pmcpmc8163742 doi102147 ppas307987,0.0
n ndimethylglycine patients progressive multiple sclerosis result pilot doubleblind placebo controlled randomized clinical trial abstractoral administration n ndimethylglycine dmg tertiary amino acid presumably enhances oxygen utilization tissue complex free radicals beneficial effects improved endurance performance reduction fatigue humans animals pilot study reports results oneyear doubleblind placebocontrolled trial dmg 30 randomized patients progressive multiple sclerosis treatment effects found placebo group dmg group disability fatigue cognitive gait parameters,0.0
research priorities multiple sclerosis latin america multistakeholder call action improve patients care research priorities ms latam abstractsas human economic resources limited especially latin america latam important identify research priorities improve multiple sclerosis ms patients care region objective generate multidisciplinary consensus research priorities ms patients care latam involving healthcare professionals ms patient associationsmethodsconsensus reached fourstep modified delphi method designed identify rate research priorities ms latam process consisted two qualitative assessments general ranking phase consensus meeting followed detailed ranking phaseresultsa total 62 participants 35 neurologists 4 nurses 12 kinesiologists 7 neuropsychologists 4 patient association members developed process final ranking stage following consensus meeting participant provided final rankings top priority research questions outlined 11 research priorities identified focusing healthcare access costs disease physical cognitive evaluation rehabilitation quality life symptoms management prognostic factors need ms care units patientnulls management emergencies like covid19conclusionthis work establishes ms research priorities latam multiple perspectives pursue actions suggested launch drive obtain information will help us better understand disease region especially better care affected patients,0.0
selfcare practices related factors patients multiple sclerosis ms based health belief model j caring sci 2021 may 24 10 2 7783 doi 1034172 jcs2021015 ecollection 2021 mayabstractintroduction selfcare programs can raise health patients multiple sclerosis ms study aimed identify selfcare behaviors determinants patients ms according health belief model hbm methods crosssectional study included 280 ms patients convenience sampling method collection tool selfadministered questionnaire based hbm participants members ms society kerman iran data analyzed using descriptive statistics path analysis multivariable linear regression spss software version 22 results mean sd score selfcare practices 286 064 medication adherence conducted practice perceived benefits cues action exerted positive influence selfcare practices frequent symptoms experienced participants fatigue 825 visual impairment 764 headaches 721 muscle weakness 714 important cues action selfcare behavior physician 77 media 52 ms patients 32 conclusion quality life qol ms patients heavily influenced selfcare behaviors study half patients accomplished selfcare behaviors seems insufficient since perceived benefits cues action main predictors selfcare practices intervention based two constructs can utilized promote selfcare programs qol ms patients healthcare providers pay attention factors promoting selfcare behaviorspmid34222116 pmcpmc8242295 doi1034172 jcs2021015,0.0
association neurodegenerative diseases periodontitis systematic review front aging neurosci 2021 may 24 13651437 doi 103389 fnagi2021651437 ecollection 2021abstractbackground neurodegenerative diseases group progressive disorders affect central nervous system cns alzheimer parkinson multiple sclerosis inflammation plays critical role onset progression injuries periodontitis considered inflammatory disease caused oral biofilms around toothsupporting tissues leading systemic chronic inflammatory condition thus systematic review aimed search evidence association neurodegenerative disorders periodontitis methods systematic review registered international prospective register systematic reviews prospero code crd 42016038327 search strategy performed three electronic databases one gray literature sourcepubmed scopus web science opengrey based peco acronym observational studies humans p neurodegenerative disease present e absent c observe association periodontitis o fowkes fulton checklist used critically appraise methodological quality risk bias individual studies quality evidence assessed grading recommendations assessment development evaluation grade results 534 articles found 12 included eight casecontrol three crosssectional one cohort giving total 3 460 participants included studies reported association neurodegenerative diseases periodontitis presented low risk bias according grade approach level evidence probing pocket depth considered low due significant heterogeneity across studies upgrading imprecision inconsistency conclusions although included studies review reported association neurodegenerative diseases periodontitis level evidence classified low suggests cautious interpretation resultspmid34108875 pmcpmc8180549 doi103389 fnagi2021651437,0.0
estimates epidemiology mortality disease burden associated progressive fibrosing interstitial lung disease france progress study background paucity data epidemiology survival estimates healthcare resource utilisation associated costs patients progressive fibrosing interstitial lung disease pfild france algorithm extracting claims data developed indirectly identify describe patients pfild french national administrative healthcare databasemethodsthe french healthcare database systme national des donnes de sant snds includes data related ambulatory care hospitalisations death 988 population study algorithms based age diagnosis healthcare consumption created identify adult patients pfild idiopathic pulmonary fibrosis 2010 2017 incidence prevalence survival estimates clinical features healthcare resource usage costs described among patients pfildresultswe identified total 14 413 patients pfild almost half 481 female mean standard deviation age 684 150 years 2010 2017 estimated incidence pfild ranged 40 47 100 000 personyears estimated prevalence 66 194 100 000 persons main diagnostic categories represented exposurerelated ild hypersensitivity pneumonitis n 3486 242 idiopathic interstitial pneumonia n 3113 216 rheumatoid arthritisassociated ild n 2521 175 median overall survival using kaplanmeier estimation 37 years start progression study 952 patients 1 hospitalisation respiratory care 343 hospitalised intensive care unit median interquartile range total specific cost per patient followup period 25 613 10 62254 287 median annual cost per patient 18 362 685652 026 11 784 300342 097 related hospitalisations limitations included retrospective design identification cases algorithm absence chest highresolution computed tomography scans pulmonary function testsconclusionsthis large realworld longitudinal study provides important insights characteristics epidemiology healthcare resource utilisation costs associated pfild france using comprehensive exhaustive database provides vital evidence pfild represents high burden patients healthcare servicestrial registration clinicaltrialsgov nct03858842 isrctn isrctn12345678 registered 3 january 2019retrospectively registered https clinicaltrialsgov ct2 show nct03858842,0.0
human endogenous retrovirus therapeutic targets neurologic disease pharmaceuticals basel 2021 may 24 14 6 495 doi 103390 ph14060495abstracthuman endogenous retroviruses hervs ancient retroviral dna sequences established germline contain regulatory elements encoded proteins may provide benefits hosts coopted cellular genes tight regulation mainly achieved epigenetic mechanisms can altered environmental factors eg viral infections leading herv activation aberrant expression hervs associates neurological diseases multiple sclerosis ms amyotrophic lateral sclerosis als inflammatory processes neurodegeneration review summarizes recent advances epigenetic mechanisms controlling herv expression pathogenic effects triggered herv derepression article ends describing new promising therapies targeting herv elements one temelimab completed phase ii trials encouraging results treating ms information gathered may turn helpful design new strategies unveil epigenetic failures behind hervtriggered diseases opening new possibilities druggable targets extending use temelimab treat associated diseasespmid34073730 doi103390 ph14060495,0.0
fourth bioelectronic medicine summit technology targeting molecular mechanisms current progress challenges charting future abstractthere broad growing interest bioelectronic medicine dynamic field continues generate new approaches disease treatment fourth bioelectronic medicine summit technology targeting molecular mechanisms took place september 23 24 2020 virtual meeting hosted feinstein institutes medical research northwell health summit called international attention bioelectronic medicine platform new developments science technology healthcare meeting arena exchanging new ideas seeding potential collaborations involving teams academia industry summit provided forum leaders field discuss current progress challenges future developments bioelectronic medicine main topics discussed summit outlined,0.0
coping profiles multiple sclerosis comparison personal resources backgroundidentifying profiles multiple sclerosis ms patients employ similar patterns coping may improve understanding coping associated psychological adjustment purpose study identify groups ms patients using different coping strategies compare levels psychological resources across groupsmethodsin crosssectional study 382 patients ms completed battery selfreport measures assessed use different coping strategies optimism selfefficacy health locus control hlc perception disease groups different coping profiles selected performing cluster analysisresultsfive different coping profiles highlighted defined follows emotional temperate active passive problem copers significant differences detected groups levels optimism selfefficacy hlc perception diseaseconclusionpatients ms use varied repertoire coping strategies allowed distinguishing coping profiles groups representing particular profiles differ terms psychological resources study contributed increasing interest investigating coping profiles identifying subgroups individuals based coping profiles recognizing differences important providing psychological support,0.0
comparison effects rituximab versus immunotherapies mogiggassociated central nervous system demyelination metaanalysis abstractbackgroundmyelin oligodendrocyte glycoprotein mog antibody disease mogad now recognised nosological entity specific clinical paraclinical features aid early diagnosis rituximab rtx chimeric monoclonal antibody directed cd20 epitope expressed preb mature b cells used treat bcellderived lymphoid neoplasms antibodymediated autoimmune diseases review performed metaanalysis evaluate rtx efficacy assessed treatment efficacies based relapse ratesmethodsthis study conducted according prisma preferred reporting items systemic review metaanalysis statement searched publications pubmed embase cochrane library clinical trials december 2020 compiled 5 studies metaanalysis forest plots conducted arr ratio change pre posttreatment rituximab disease modifying drugs sensitivity analysis performed mean difference md efficacy rtx versus immunotherapies subgroup analysis also performed based site studyresultsa metaanalysis 5 studies 239 participants conducted patients received rituximab recorded 82 239 3431 mean difference arr ratio rituximab therapy versus immunotherapies 016 95ci 015 047 studies found significantly affect heterogeneity major differences occurred 92 china patients 95 ci 020186 i20 908 non china patients 95 ci 024042 i20 meanwhile significant subgroup difference p018 themconclusionrtx reduces relapse frequency patients mog antibody disease differences rituximab immunotherapies mog antibody disease future large multicenter randomized controlled clinical trial thoroughly characterize efficacy rituximab mog antibody disease necessary,1.0
geographic heterogeneity association varicellazoster virus seropositivity multiple sclerosis systematic review metaanalysis abstractbackground although long suspected association varicellazoster virus vzv multiple sclerosis ms connection remained unclear study performed metaanalysis attempt assess association vzv igg serostatus msmethods literature search performed using three databases medline embase cochrane eligible results included observational studies investigating seroprevalence vzv immunoglobulin g igg adults ms versus nonms controls two authors performed screen search results evaluating quality relevant outcomes using randomeffect model estimated pooled odds ratios ors 95 confidence intervals cis results literature search yielded 1 268 articles 8 2 266 ms patients 1 818 controls eligible inclusion metaanalysis evaluation included studies together showed significant association vzv igg seropositivity ms 1439 95ci 05034118 p 0497 however analyzed subgroups based geographical area studies performed asian countries showed vzv igg seropositivity common ms patients controls 4470 95ci 195910203 p 0001 significant association found european countriesconclusions study found evidence association vzv igg seropositivity ms asian countries additional studies warranted ascertain factors impacting association,0.0
flow cytometry evaluation cd14 cd16 monocyte subpopulations systemic sclerosis patients cross sectional controlled study background systemic sclerosis ssc chronic autoimmune disease characterized vasculopathy fibrosis can subclassified diffuse cutaneous dssc limited cutaneous lssc subtypes previous studies suggest increase monocytes can hallmark various inflammatory diseases including ssc aim evaluate circulating blood monocyte subpopulations classical intermediate nonclassical ssc patients possible association disease manifestationsmethodsfifty consecutive patients fulfilling 2013 acr eular classification criteria ssc included crosssectional study monocyte subpopulations identified based expression cd64 cd14 cd16 evaluated flow cytometry correlated clinical characteristics patients furthermore expression hladr cd163 cd169 cd206 monocytes studied thirtyeight age sexmatched healthy individuals recruited control groupresultsssc patients increased number circulating peripheral blood monocytes activated phenotypic profile compared healthy subjects absolute counts cd16+ intermediary nonclassical monocyte subpopulations higher ssc patients association monocyte subpopulations clinical manifestations evaluatedconclusionwe identified higher counts monocyte subpopulations ssc patients compared control group association monocyte subpopulations major fibrotic manifestations cd169 shown representative dssc promising marker differentiating disease subtypes,0.0
three chemotypes thyme thymus vulgaris l essential oil main compounds affect differently il6 tnf cytokine secretions bv2 microglia modulating nfb c ebp signalling pathways background essential oils possess antimicrobial antiinflammatory effects therefore can provide effective treatment infections essential oils widely used supportive ingredients many diseases especially acute chronic diseases respiratory tract neuroinflammation responsible several diseases central nervous system plantderived bioactive molecules shown role attenuating neuroinflammation regulating microglia immune cells cnsmethodsin study antiinflammatory effect three chemotypes thyme essential oil main compounds geraniol thujanol linalool examined lipopolysaccharideinduced bv2 microglia three different experimental setups used lps pretreatment essential oil pretreatment cotreatments lps essential oils order determine whether essential oils able prevent inflammation can decrease concentrations secreted tumour necrosis factor tnf interleukin6 il6 proinflammatory cytokines measured analysed western blot activity cell signalling pathways nfb ccaatenhancer binding protein c ebp regulating tnf il6 proinflammatory cytokine expressions bv2 cellsresultsour results showed definite alterations effects essential oil chemotypes main compounds different experimental setups considering changes il6 tnf secretions best reduction inflammatory cytokines reached pretreatment essential oils addition main compounds exerted better effects essential oil chemotypes case lps pretreatment essential oil pretreatment experiment effect linalool geraniol outstanding major difference actions chemotypes standards main compounds seen large inhibitory effects certain cell signalling components related activation expression proinflammatory cytokinesconclusionthyme essential oils good candidates use prevention neuroinflammation related neurodegeneration exact ratio components selected carefully,0.0
whole brain 3d mr fingerprinting multiple sclerosis pilot study background mr fingerprinting mrf novel imaging method proposed diagnosis multiple sclerosis ms study aims determine mr fingerprinting mrf relaxometry can differentiate frontal normal appearing white matter fnawm splenium patients diagnosed ms compared controls characterize relaxometry demyelinating plaques relative time diagnosismethodsthreedimensional 3d mrf data acquired 30t mri system resulting isotropic voxels 1 1 1 mm3 total acquisition time 4 min 38 s data collected 18 subjects paired 18 controls regions interest drawn mrfderived t1 relaxometry maps encompassing selected ms lesions fnawm splenium t1 t2 relaxometry features segmented areas used classify ms lesions fnawm splenium tdistributed stochastic neighbor embedding algorithms partial least squares discriminant analysis performed discriminate nawm splenium ms compared controlsresultsmean outoffold machine learning prediction accuracy discriminant results ms patients controls fnawm 65 p 021 approached 90 p 001 splenium significant positive correlation time since diagnosis ms lesions mean t2 p 0015 minimum t1 p 003 negative correlation splenium uniformity p 004 perfect discrimination auc 1 achieved selected features ms lesions fnawmconclusions3dmrf ability differentiate ms controls based relaxometry properties fnawm splenium whole brain coverage allows assessment quantitative properties within lesions provide chronological assessment time ms diagnosis,1.0
coping stress first wave covid19 pandemic turkish people multiple sclerosis relationship perceived stress quality life abstractbackgroundmultiple sclerosis ms chronic inflammatory disease acute exacerbations also part clinical course presence disease relapses cause stress people ms pwms reason stress coping strategies patients important reducing perceived stress aim study evaluate strategies pwms use covid19 pandemic effect strategies perceived stress relationship relapses role quality life qol methodsan online form including perceived stress scale pss 10 items coping experienced problems scale briefcope 28 items sf12 sent 340 pwms followupresultsduring covid19 pandemic found patients used strategies turn religion planning acceptance high rate pss score high 23 112 patients patients low perceived stress used acceptance strategy p0008 found negative correlation physical component summary pcs sf12 denial r02 p0001 distraction r 01 p004 negative correlation found mental component summary mcs sf12 behavioral disconnection r02 p0006 positive correlation mcs humor r01 p004 use instrumental support r02 p0009 planning r01 p004 positive reframing r02 p0002 conclusionpwms successful coping stress first half pandemic combination emotional problemfocused strategies acceptance strategy highly adopted patients low pss tendency use active coping strategy together acceptance strategy high patients without relapses adoption emotional strategies may prevented severe deterioration qol study group early period covid19 pandemic,0.0
identifying degenerative effects repetitive head trauma neuroimaging clinicallyoriented review background scope reviewvarying severities frequencies head trauma may result dynamic acute chronic pathophysiologic responses brain heightened attention longterm effects head trauma particularly repetitive head trauma sparked recent efforts identify neuroimaging biomarkers underlying disease processes imaging modalities like structural magnetic resonance imaging mri positron emission tomography pet clinically applicable given use neurodegenerative disease diagnosis differentiation recent years researchers targeted repetitive head trauma cohorts hopes identifying vivo biomarkers underlying biologic changes might ultimately improve diagnosis chronic traumatic encephalopathy cte living persons populations often include collision sport athletes eg american football boxing military veterans repetitive lowlevel blast exposure provide clinicallyoriented review neuroimaging data repetitive head trauma cohorts based structural mri fdgpet apet taupet supplement review two patient reports neuropathologyconfirmed clinically impaired adults prior repetitive head trauma underwent structural mri fdgpet apet taupet addition comprehensive clinical examinations deathreview conclusionsgrouplevel comparisons controls without known head trauma revealed inconsistent regional volume differences possible propensity medial temporal limbic subcortical thalamus corpus callosum structures greater frequency severity ie length cavum septum pellucidum csp observed repetitive head trauma cohorts compared unexposed controls remains unclear whether csp predicts particular neurodegenerative process csp presence increase suspicion clinical impairment least partly attributable individuals head trauma exposure regardless underlying disease pet imaging similarly revealed prototypical metabolic molecular pattern associated repetitive head trauma predictive cte based widely studied radiotracers given range clinical syndromes neurodegenerative pathologies observed subset adults prior repetitive head trauma structural mri pet imaging may still useful differential diagnosis eg assessing suspected alzheimers disease,0.0
comparative efficacy singlesession empowered relief videoconferencedelivered group intervention chronic pain study protocol randomized controlled trial background chronic pain naturally aversive often distressing patients pain coping selfregulatory skills shown effectively reduce painrelated distress symptoms trial primary goal pilot test comparative efficacy singlesession videoconferencedelivered group pain education class waitlist control among patients chronic painmethodsour study randomized clinical trial pilot testing superiority 2h singlesession videoconferencedelivered group pain education class waitlist control will enroll 120 adult patients mixed etiology chronic pain randomize 11 one two study arms hypothesize superiority pain education class bolstering pain symptom management team researchers masked treatment assignment will assess outcomes 3 months posttreatmentdiscussionthis study aims test utility singlesession videoconferencedelivered group pain education class improve selfregulation pain painrelated outcomes findings project potential significantly reduce barriers effective psychological treatment pain optimizing delivery increasingly vital online remotedelivered intervention optionstrial registrationclinicaltrialsgovnct04546685 registered 04 september 2020,0.0
lifestyle exercise activity package people living progressive multiple sclerosis leapms protocol singlearm feasibility study background codesigned tailored blended physiotherapy intervention people progressive multiple sclerosis pwpms often struggle access support physical activity underpinned selfmanagement principles lifestyle exercise activity package people multiple sclerosis leapms intervention incorporates facetoface online physiotherapy coaching sessions accompanying online physical activity platform leapms platform multiuser system enabling user physiotherapist cocreate activity plans leapms platform consists information activity suite interactive components enabling selection exercises activity programme goal setting activity logging platform also facilitates online remote support physiotherapist embedded online messaging function aim evaluate leapms platform feasibility trialmethodsleapms will evaluated within singlearm feasibility study embedded process evaluation registration initial eligible screening 21 participants will required complete baseline selfcompletion measures will followed initial homebased online coaching session physiotherapist received tailored selfmanagement digital resource training access online intervention initial 3month period period participants given option request five homebased online physiotherapy coaching sessions followup questionnaires semistructured interviews will administered 3 months baseline participants intervention physiotherapists leapms platform will available participants 3 months usage leapms platform will tracked full 6month period final followup will conducted 6 months baselinediscussionfeasibility outcomes recruitment retention intervention uptake safety will reported process evaluation will undertaken identify possible mechanisms observed effects data will inform fullscale evaluations coproduced blended physiotherapy interventiontrial registrationclinicaltrialsgov nct03951181 registered 15 may 2019,0.0
effect fingolimod vs interferon treatment oct measurements cognitive function rrms abstractobjectiveto explore prospectively oct rate retinal layer changes relapsingremitting multiple sclerosis patients followed fingolimod interferon well treatmentsnull differential effects cognitive tests scoresmethodsthis prospective observational study enrolled 128 stable rrms patients treated either fingolimod n71 interferon n56 symboldigit modality test retinal oct scans obtained baseline every 6 12 months subgroup patients underwent expanded cognitive tests annually brief visualspatial memorytotal recall bvmtdelayed recall montreal cognitive assessment retinaloct scans also obtained 22 age sexmatched healthy controls mixed effects regression used study annualized changes retinal layers cognitive function including differences treatment groups correlations annualized changes retinal measurements cognitive scores also exploredresultsfingolimod treated patients showed significant difference rate thinning retinal layers compared healthy controls significantly less gcipl thinning compared interferons sdmt scores improved similarly among rrms treatment groups however interferon fingolimod treated patients significant decline moca total recall scores also found correlations annualized change gcipl thickness annualized change moca scores similar correlations annualized change total recall scoresconclusionfingolimod potential role reducing retinal neurodegeneration rrms longitudinal oct measures appear sensitive changes cognitive function may useful monitoring neuroprotective therapies,1.0
anticd20 depletes meningeal b cells halt formation meningeal ectopic lymphoid tissue neurol neuroimmunol neuroinflamm 2021 may 21 8 4 e1012 doi 101212 nxi0000000000001012 print 2021 jul 2abstractobjective investigate whether anticd20 bcelldepleting monoclonal antibodies cd20 mabs inhibit formation retention meningeal ectopic lymphoid tissue melt murine model multiple sclerosis ms methods used spontaneous chronic experimental autoimmune encephalomyelitis eae model mice mutant tcell bcell receptors specific myelin oligodendrocyte glycoprotein mog develop meningeal inflammatory infiltrates resembling described ms cd20 mabs administered either preventive treatment regimen extent cellular composition melt assessed histology immunohistochemistryresults cd20 mab applied paradigm either prevent treat eae alter disease course either condition however cd20 mab depleted virtually b cells meningeal compartment failed prevent formation melt altogether absence b cells melt less densely populated immune cells cellular composition changed increased neutrophil granulocytesconclusions results demonstrate cns autoimmune disease meningeal inflammatory infiltrates may form persist absence b cells together finding cd20 mab ameliorate spontaneous chronic eae melt data suggest melt may yet unknown capacities independent b cells contribute cns autoimmunitypmid34021057 doi101212 nxi0000000000001012,1.0
identification key genes calcific aortic valve disease via weighted gene coexpression network analysis background calcific aortic valve disease cavd common subclass valve heart disease elderly population primary cause aortic valve stenosis however underlying mechanisms remain unclearmethodsthe gene expression profiles gse83453 gse51472 gse12644 analyzed limma weighted gene coexpression network analysis wgcna package r identify differentially expressed genes degs key modules associated cavd respectively enrichment analysis performed based gene ontology go kyoto encyclopedia genes genomes kegg pathway disgenet trrust database proteinprotein interaction network constructed using overlapped genes degs key modules identified top 5 hub genes mixed character calculationresultswe identified blue yellow modules key modules enrichment analysis showed leukocyte migration extracellular matrix extracellular matrix structural constituent significantly enriched spp1 tnc scg2 fam20a cd52 identified hub genes expression levels calcified normal aortic valve samples illustrated respectivelyconclusionsthis study suggested spp1 tnc scg2 fam20a cd52 might hub genes associated cavd studies required elucidate underlying mechanisms provide potential therapeutic targets,0.0
use diseasemodifying therapies pediatric relapsingremitting multiple sclerosis united kingdom neurol neuroimmunol neuroinflamm 2021 may 21 8 4 e1008 doi 101212 nxi0000000000001008 print 2021 julabstractobjectives compare realworld effectiveness newer diseasemodifying therapies dmts vs injectables children relapsingremitting multiple sclerosis rrms methods retrospective multicenter study uk childhood inflammatory demyelination network identified children rrms receiving dmts january 2012 december 2018 clinical paraclinical data retrieved medical records annualized relapse rates arrs treatment time relapse time new mri lesions change expanded disability status scale edss score calculatedresults 103 children treated dmts followed 38 years relapses treatment recorded 53 89 595 injectables vs 8 54 15 newer dmts arr reduced 19 11 injectables p 0001 vs 16 03 newer dmts p 0002 new mri lesions occurred 77 89 865 patients injectables vs 26 54 47 newer dmts p 00001 children newer dmts showed longer time relapse time switch treatment time new radiologic activity patients injectables logrank p 001 adjustment potential confounders multivariable analysis showed injectables associated 12fold increased risk clinical relapse adjusted hazard ratio hr 1212 95 ci 1648987 p 0015 2fold increased risk new radiologic activity adjusted hr 278 95 ci 108713 p 0034 compared newer dmts 2 years treatment initiation 38 103 37 patients mri activity absence clinical relapses edss score change followup 2 patients cognitive impairmentconclusion newer dmts associated lower risk clinical radiologic relapses patients compared injectables study adds weight argument imminent shift practice toward use newer efficacious dmts first instanceclassification evidence study provides class iv evidence newer dmts oral infusions superior injectables interferon beta glatiramer acetate reducing clinical relapses radiologic activity children rrmspmid34021056 doi101212 nxi0000000000001008,1.0
brain barriers brain fluids research 2020 fluids barriers cns thematic series advances vitro modeling bloodbrain barrier neurovascular unit abstractthis editorial discusses advances brain barrier brain fluid research 2020 topics include cerebral endothelium neurovascular unit choroid plexus meninges cerebrospinal fluid glymphatic system disease states impacting brain barriers brain fluids drug delivery brain editorial also highlights recently completed fluids barriers cns thematic series entitled advances vitro modeling bloodbrain barrier neurovascular unit vitro modeling progressing rapidly,0.0
network damage predicts clinical worsening multiple sclerosis 64year study neurol neuroimmunol neuroinflamm 2021 may 21 8 4 e1006 doi 101212 nxi0000000000001006 print 2021 julabstractobjective multiple sclerosis ms clinical impairment likely due structural damage abnormal brain function assessed added value integrating structural functional network mri measures predict 64year ms clinical disability deteriorationmethods baseline 3d t1weighted restingstate functional mri scans obtained 233 patients ms 77 healthy controls patients underwent neurologic evaluation baseline 64year median followup interquartile range 506751 years followup patients classified clinically stable worsened according disability changes relapsingremitting rr ms secondary progressive sp ms conversion evaluated global brain volumetry obtained furthermore independent component analysis identified main functional connectivity fc gray matter gm network patternsresults followup 105 233 45 patients clinically worsened 26 157 16 patients rrms evolved spms treatmentadjusted random forest model identified normalized gm brain volumes decreased fc defaultmode networks increased fc left precentral gyrus sensorimotor network smn gm atrophy frontoparietal network false discovery rate fdr corrected p range 001009 predictors clinical worsening outofbag oob accuracy 074 expected contribution baseline disability also present fdrp 001 baseline disability normalized gm volume gm atrophy smn fdrp range 001009 independently associated spms conversion oob accuracy 084 receiver operating characteristic analysis including network mri variables improved disability worsening p 005 spms conversion p 002 predictionconclusions integration mri network measures helped determining relative contributions global local gm damage functional reorganization clinical deterioration mspmid34021055 doi101212 nxi0000000000001006,0.0
mesenchymal stem stromal cellderived exosomes regenerative medicine cancer overview development challenges opportunities abstractrecently mesenchymal stem stromal cells mscs widespread biomedical applications attracted great consideration scientific community around world however reports shown main populations transplanted mscs trapped liver spleen lung upon administration highlighting importance development cellfree therapies concerning rising evidence suggesting beneficial effects msc therapy closely linked mscreleased components predominantly mscderived exosomes development mscbased cellfree approach paramount importance exosomes nanosized 30100 nm lipid bilayer membrane vesicles typically released mscs found different body fluids include various bioactive molecules messenger rna mrna micrornas proteins bioactive lipids thus showing pronounced therapeutic competence tissues recovery maintenance endogenous stem cells enhancement regenerative phenotypic traits inhibition apoptosis concomitant immune modulation stimulation angiogenesis conversely specific roles msc exosomes treatment various tumors remain challenging development clinical application novel mscbased cellfree strategies can supported better understanding mechanisms classifying subpopulation exosomes enhancing conditions cell culture isolation increasing production exosomes along engineering exosomes deliver drugs therapeutic molecules target sites current review deliver brief overview mscderived exosome biogenesis composition isolation methods discuss recent investigation regarding therapeutic potential msc exosomes regenerative medicine accompanied doubleedged sword role cancer,0.0
17estradiol reduces demyelination cuprizonefed mice promoting m2 microglia polarity regulating nlrp3 inflammasome neuroscience 2021 mar 29s03064522 21 001585 doi 101016 jneuroscience202103025 online ahead printabstractestrogen produces beneficial role animal models multiple sclerosis ms effect 17estradiol therapy microglia polarization neuroinflammation corpus callosum cuprizoneinduced demyelination model elucidated study mice given 02 cuprizone cpz 5 weeks induce demyelination received 50 ng 17estradiol est injected subcutaneously neck region twice weekly data revealed treatment 17estradiol therapy cpz+est improved neurological behavioral deficits displayed significant reduction escape latencies comparison untreated cpz mice also administration 17estradiol caused decrease demyelination levels axonal injury demonstrated staining luxol fast blue immunofluorescence myelin basic protein transmission electron microscopy analysis addition transcriptional level brain mice treated 17estradiol cpz+est showed decrease levels m1assosicted microglia markers cd86 inos mhcii whereas m2associated genes arg1 cd206 trem2 increased compared cpz mice moreover administration 17estradiol resulted significant reduction 3fold transcript levels nlrp3 inflammasome downstream product il18 comapred controls summary study demonstrated first time exogenous 17estradiol therapy robustly leads reduction m1 phenotype stimulation polarized m2 microglia repression nlrp3 inflammasome corpus callosum cpz demyelination model ms positive effects 17estradiol microglia inflammasome seems facilitate accelerate remyelination processpmid33794337 doi101016 jneuroscience202103025,1.0
impact covid19 pandemic headache symptoms drug withdrawal among patients medication overuse headache crosssectional study background coronavirus disease 2019 covid19 bring range psychological distress symptom deterioration headache patients especially migraineurs compared migraineurs normal control medication overuse headache moh patients likely experience worse psychological distress poorer outcome noncovid19 time however covid19 pandemic whether moh patients greater physical mental symptom deterioration worse relief headache symptoms medications overuse remained unclear aim investigate impact covid19 moh patients guide better management studymethodswe enrolled moh patients diagnosed treated headache clinic west china hospital information prepandemic 3 months period covid19 pandemic period collected univariate multivariate logistic regression performed identify independent factors associated changes headache symptoms drug withdrawalresultsseventyeight moh patients enrolled study ultimately comparison prepandemic period fewer moh patients reported decreased headache days intensity days acute medications per month pandemic available access regular prophylactic medications significantly associated reduction least 50 headache days decrease headache intensity per month respective odds ratios 3919 95 ci 37540915 p 0002 1013 95 ci 2334412 p 0002 following abrupt withdrawal high educational level significant factors decreasing headache intensity male sex significantly associated decrease days acute medication per month pandemic odds ratios 478 95ci 1441587 p 0011 conclusionsour findings reflect moh patients experienced worse relief headache symptoms drug withdrawal pandemic available access regular prophylactic medications significant independent factor improvement headache symptoms male sex significantly associated decreased days acute medications per month,0.0
human trnaguanine transglycosylase displays promiscuous nucleobase preference strict trna specificity nucleic acids res 2021 may 1gkab289 doi 101093 nar gkab289 online ahead printabstractbasemodification can occur throughout transfer rna molecule however elaboration particularly prevalent position 34 anticodon loop wobble position functions influence protein translation previously demonstrated queuosine modification position 34 can substituted artificial analogue via queuine trna ribosyltransferase enzyme induce disease recovery animal model multiple sclerosis demonstrate human enzyme can recognize broad range artificial 7deazaguanine derivatives transfer rna incorporation contrast enzyme displays strict specificity transfer rna species decoding dual synonymous nau c codons determined using novel enzymerna capturerelease method data highlight broad scope therapeutic potential exploiting queuosine incorporation pathway intentionally engineer chemical diversity transfer rna anticodonpmid34009357 doi101093 nar gkab289,0.0
comparison upper limb function subjects multiple sclerosis healthy controls using inertial measurement unit abstractupper limbs ul dysfunction frequent people multiple sclerosis pwms several objective measures ul function proposed however use mostly confined assess subjects mildtomoderate disability requires fine motor skills often impaired high disability level subjects thus tool score ul function advanced disease stage lackingthe aim study analyse compare ul unilateral bilateral movements healthy control hc pwms different disability levels using instrumented version inertial measurement unit imu 15seconds fingertonose test fnt movement cycle segmented going adjusting returning phases interhand interval ihi allowed assessing bilateral coordination ie synchrony phase larger ihi severe bilateral coordination impairment isafter stratifying pwms disability level pwmslow expanded disability status scale edss55 pwmshigh edss6 anova ihi showed significant differences pwms hc p0001 phases however going phase ihi showed significantly higher asynchrony pwmshigh pwmslow hc p0001 differences pwmslow hc going phase ihi seems clinical marker specific high disability level pwmsthese findings suggest inertial sensors fnt easytouse method detailed quantitative characterization ul function pwms also subjects edss greater 6,0.0
longitudinal changes financial hardship patients multiple sclerosis abstractobjective measure longitudinal changes three domains financial hardship ie financial worry costrelated care nonadherence material hardship patients msmethods convenience sample 559 adult patients known diagnosis ms visiting single outpatient neurology clinic july 2018 february 2020 approached patients completed surveys baseline 3 6 9 12 months postenrollment outcomes included financial worry using comprehensive score financial toxicity patientreported outcome cost cumulative costrelated care nonadherence cumulative financial hardship adopted medical expenditure panel survey meps associations financial worry care nonadherence material hardship assessed using anovaresults total 242 433 participated baseline mean age 436136 years 769 female 464 white median months diagnosis 63 iqr 28120 mean cost score enrollment 1743 1015 increased 1941 1112 12 months p009 cumulative costrelated ms care nonadherence increased 326 baseline 533 12 months 207 increase p 0001 cumulative material hardship increased 616 baseline 760 12 months 144 increase p0001 changes cost score baseline 12 months significantly associated changes nonadherence material hardship p001 conclusion relevance costrelated care nonadherence material hardship accumulate progressively time correlates financial worry clinical practices focus screening risk intervene goal mitigating costs care improving patient outcomes,0.0
epidemiology multiple sclerosis sultanate oman hospital based study abstractbackgroundthe prevalence multiple sclerosis ms changing globally also individual countries aim estimate prevalence ms omani population period 20062019 well incidence 20152018methodsthis retrospective observational hospitalbased study ms patients diagnosed per revised mcdonald criteria period june 2006 may 2019 information reviewed age disease onset gender year diagnosis obtained population oman national census dataresultsa total 422 patients diagnosed ms study period population oman per 2019 census data 2 652 199 estimated crude prevalence 159 95 confidence interval 144 175 per 100 000 female male ratio 2171 mean age disease onset 273 77 range 9 59 years 83 patients first clinical manifestation age 19 40 years 9 disease onset 19 years annual incidence increased 100 case per 100 000 2015 138 cases per 100 000 2018conclusionthe prevalence ms omani population 159 per 100 000 placing oman medium risk zone,0.0
fine particulate matter related multiple sclerosis relapse young patients front neurol 2021 may 21 12651084 doi 103389 fneur2021651084 ecollection 2021abstractobjective particulate matter pm aerodynamic diameter smaller 10 m pm10 associated multiple sclerosis ms relapse however impact smaller pm greater ability penetrate human organism never assessed evaluated impact pm smaller 25 m pm25 risk ms relapse material methods casecrossover study included 2 109 consecutive hospitalizations likely due ms relapse day hospital 5 ms centers paris area january 2009 december 2013 hospitalization natural logarithm average weekly pm25 concentrations g m3 patients residence address 6 weeks week 0 week 5 preceding admission compared concentration previous week using conditional logistic regression adjusted temperature flulike syndrome rate pollen count holiday period results pm25 average concentration week 3 significantly associated risk hospitalization ms relapse 121 ci 101 146 association stronger patients younger 30 years or177 ci 110 283 conclusion study demonstrates association exposure pm25 ms relapse particularly young peoplepmid34093398 pmcpmc8176031 doi103389 fneur2021651084,0.0
differentiation multiple sclerosis neuromyelitis optica spectrum disorder using optical coherence tomography angiography sci rep 2021 may 21 11 1 10697 doi 101038 s41598021900366abstractneuromyelitis optica spectrum disorder nmosd multiple sclerosis ms autoimmune demyelinating diseases distinct etiology presenting optic neuritis study aimed identify macular peripapillary neurovascular alterations may facilitate differentiation nmosd ms eyes using spectraldomain optical coherence tomography oct oct angiography octa total 13 nmosd patients 40 ms patients evaluated radial peripapillary capillary rpc vessel density significantly decreased superior s inferior sectors nmosd compared ms eyes whereas nonon eyes temporal t sector rpc reduced ms group eyes retinal nerve fiber layer t quadrants thinner nmosd ms regarding nonon eyes macular capillary plexuses ganglion cell complex thickness differ nmosd ms ratios based diseasespecific intraeye rpc vessel density reduction pattern best discriminants nmosd ms ie inferior nasal n t ratios eyes s t n t ratios nonon eyes results show octabased simple ratios may useful distinguishing nmosd ms patientspmid34021191 doi101038 s41598021900366,1.0
synaptic fus accumulation triggers early misregulation synaptic rnas mouse model als nat commun 2021 may 21 12 1 3027 doi 101038 s41467021231888abstractmutations disrupting nuclear localization rnabinding protein fus characterize subset amyotrophic lateral sclerosis patients alsfus fus regulates nuclear rnas role synapse poorly understood using superresolution imaging determined localization fus within synapses occurs predominantly near vesicle reserve pool presynaptic sites using clipseq synaptoneurosomes identified synaptic fus rna targets encoding proteins associated synapse organization plasticity significant increase synaptic fus early disease mouse model als accompanied alterations density size gabaergic synapses mrnas abnormally accumulated synapses 6monthold alsfus mice enriched fus targets correlated depicting increased shortterm mrna stability via binding primarily multiple exonic sites study indicates synaptic fus accumulation early disease leads synaptic impairment potentially representing initial trigger neurodegenerationpmid34021139 doi101038 s41467021231888,0.0
crossed brainstem syndrome revealing bleeding brainstem cavernous malformation illustrative case background since nineteenth century great variety crossed brainstem syndromes cbs described medical literature cbs typically combines ipsilateral cranial nerves deficits contralateral long tracts involvement hemiparesis hemianesthesia classical cbs seem fact clearcut entities 20 patients showing different unnamed combinations crossed symptoms terms etiologies acute brainstem infarction predominates cbs secondary hemorrhage neoplasm abscess demyelination described aim study assess proportion cbs caused bleeding episode arising brainstem cavernous malformation bcm reported literaturecase presentationwe present case typical foville syndrome 65yearold man caused pontine bcm extralesional bleeding following first bleeding episode conservative management decided patient eventually operated soon second bleeding eventdiscussiona literature review conducted focusing five common cbs benedikt weber foville millardgubler wallenberg medline database inception 2020 according literature hemorrhagic bcm account approximately 7 cbs microsurgical excision may indicated second bleeding episode needs carefully weighted risks surgical procedure openly discussed patientconclusionsin setting cbs neuroimaging workup may infrequently reveal bcm requiring complex multidisciplinary team management including neurosurgical advice,1.0
novel lysolecithin model visualizing damage vivo larval zebrafish spinal cord front cell dev biol 2021 may 20 9654583 doi 103389 fcell2021654583 ecollection 2021abstractbackground lysolecithin commonly used induce demyelinating lesions spinal cord corpus callosum mammalian models although models clinical patient samples used study neurodegenerative diseases multiple sclerosis ms allow direct visualization diseaserelated damage vivo overcome limitation created characterized focal lysolecithin injection model zebrafish allows us investigate temporal dynamics underlying lysolecithininduced damage vivo results injected lysolecithin 46 days postfertilization dpf zebrafish larval spinal cords coupled vivo timelapse imaging observed hallmarks consistent mammalian models lysolecithininduced demyelination including myelinating glial cell loss myelin perturbations axonal sparing debris clearance conclusion developed characterized lysolecithin injection model zebrafish allows us investigate myelin damage living vertebrate organism model may useful preclinical screening tool investigating safety efficacy novel therapeutic compounds reduce damage promote repair neurodegenerative disorders mspmid34095120 pmcpmc8173112 doi103389 fcell2021654583,1.0
guideline ultrasonic diagnosis liver diseases zhonghua gan zang bing za zhi 2021 may 20 29 5 385402 doi 103760 cmajcn5011132021021900087abstractultrasound noninvasive realtime inexpensive radiationfree easily repeatable method usually used liver imaging recent years new ultrasound examination techniques liver diseases contrastenhanced ultrasound elastography rapidly developed can effectively identify intrahepatic spaceoccupying lesions assess degree liver fibrosis portal hypertension monitor effects treatment therefore technologies play important diagnostic role clinical liver diseases therapeutic interventional value guideline classifies instrument setup patient preparation physician examination methods multimodal ultrasound examinations grayscale ultrasound color doppler ultrasound contrastenhanced ultrasound elastic ultrasound liver diseases addition liver diseases multimodal ultrasound technology diagnostic criteria diffuse hepatic lesions inflammatory lesions fibrosis sclerosis multiple spaceoccupying lesions interventional procedures defined standardized concurrently also recommend ultrasound monitoring time interval diagnostic report writing standard liver diseasespmid34107574 doi103760 cmajcn5011132021021900087,0.0
role cannabidiol therapeutic intervention substance use disorders front pharmacol 2021 may 20 12626010 doi 103389 fphar2021626010 ecollection 2021abstractdrug treatments available management substance use disorders sud present multiple limitations efficacy lack approved treatments alarming relapse rates facts hamper clinical outcome quality life patients supporting importance develop new pharmacological agents lately several reports suggest cannabidiol cbd presents beneficial effects relevant management neurological disorders epilepsy multiple sclerosis parkinsons alzheimers diseases furthermore large body evidence pointing cbd improves cognition neurogenesis presents anxiolytic antidepressant antipsychotic neuroprotective effects suggesting potential usefulness treatment neuropsychiatric diseases sud review preclinical clinical reports regarding effects cbd regulation reinforcing motivational withdrawalrelated effects different drugs abuse alcohol opioids morphine heroin cannabinoids nicotine psychostimulants cocaine amphetamine furthermore special section review focused neurobiological mechanisms might underlying antiaddictive action cbd regulation dopaminergic opioidergic serotonergic endocannabinoid systems well hippocampal neurogenesis multimodal pharmacological profile described cbd specific regulation addictive behaviorrelated targets explains least part therapeutic effects regulation reinforcing motivational properties different drugs abuse moreover remarkable safety profile cbd lack reinforcing properties existence approved medications containing compound sativex epidiolex increased number studies suggesting potential cbd therapeutic intervention sud rising number publications substantial results valuable therapeutic innovation cbd treating sud undeniable need new therapeutic agents improve clinical outcome patients sud upcoming clinical trials involving cbd endorse relevance reviewpmid34093179 pmcpmc8173061 doi103389 fphar2021626010,0.0
author correction identifying multiple sclerosis subtypes using unsupervised machine learning mri data nat commun 2021 may 20 12 1 3169 doi 101038 s41467021235386no abstractpmid34016975 doi101038 s41467021235386,0.0
prevalence severity clinical management brain incidental findings healthy young adults mrishare crosssectional study front neurol 2021 may 20 12675244 doi 103389 fneur2021675244 ecollection 2021abstractbackground objectives young adults represent increasingly large proportion healthy volunteers brain imaging research descriptions incidental findings ifs age group scarce aimed assess prevalence severity ifs brain mris healthy young research participants aged 1835 years describe protocol implemented handle methods study population comprised 1 867 participants aged 221 23 years 72 women mrishare crosssectional brain mri substudy ishare student cohort ifs flagged mri quality control estimated proportion participants ifs requiring medical referral potentially serious psifs defined uk biobank overall type severity final diagnosis well number ifs results 78 1 867 participants least one 42 95 confidence interval ci 3452 ifs requiring medical referral n 38 observed 36 1 867 participants 19 1427 represented 475 80 ifs initially flagged referred ifs retrospectively classified psifs 25 1 867 participants 13 0920 accounting 684 anomalies referred 26 38 common final diagnosis cysts ventricular abnormalities participants 9 1 867 05 0209 referred ifs 9 36 250 136413 multiple sclerosis radiologically isolated syndrome participants psifs 5 19 263 115491 represented 01 0004 02 00305 participants respectively final diagnoses considered serious 11 1 867 participants 06 0311 among participants referred ifs 139 5 36 required active intervention 500 18 36 put clinical surveillance conclusions large brain imaging study young healthy adults participating research observed nonnegligible frequency ifs etiological pattern differed described older adultspmid34093421 pmcpmc8173138 doi103389 fneur2021675244,0.0
variation vulnerability mice expressing human superoxide dismutase 1 prionlike seeding study influence primary amino acid sequence abstractmisfolded forms superoxide dismutase 1 sod1 mutations associated familial amyotrophic lateral sclerosis fals exhibit prion characteristics including ability act seeds accelerate motor neuron disease mouse models key feature infectious prion seeding efficiency transmission governed primary sequence prion protein prp isologous seeding sequence prp seed matches host generally much efficient sequence mismatch used paradigms mutant sod1 seeding homogenates injected intraspinally newborn mice sciatic nerve adult mice assess influence sod1 primary sequence seeding efficiency observed spectrum seeding efficiencies depending upon sod1 expressed mice injected seeds origin seed preparations mice expressing wt human sod1 disease variant g37r resistant isologous seeding mice expressing g93a sod1 also largely resistant isologous seeding limited success one line mice express low levels contrast mice expressing human g85rsod1 highly susceptible isologous seeding resistant heterologous seeding homogenates paralyzed mice overexpressing mouse sod1g86r seeding experiments g85r sod1yfp mice observed homogenates paralyzed animals expressing h46r g37r variants human sod1 less effective seeds prepared mice expressing human g93a variant sequence mismatch effects less pronounced used purified recombinant sod1 fibrilized vitro seeding preparation collectively findings demonstrate diversity abilities als variants sod1 initiate sustain prionlike propagation misfolded conformations produce motor neuron disease,0.0
antidepressants multiple sclerosis review vitro vivo models front immunol 2021 may 20 12677879 doi 103389 fimmu2021677879 ecollection 2021abstractbackground increased prevalence depression observed among patients multiple sclerosis ms correlated elevated levels proinflammatory cytokines overall deregulation monoaminergic neurotransmitters patients exhibit antidepressants proved effective treating depression comorbid ms also alleviating numerous ms symptoms even minimizing stressrelated relapses therefore agents prospectively prove beneficial complementary ms therapyobjective review aims illustrating underlying mechanisms involved beneficial clinical effects antidepressants observed ms patientsmethods literature search screened comparatively assessed papers effects antidepressant use vitro vivo ms models taking account number inclusion exclusion criteriaresults vitro studies indicated antidepressants promote neural glial cell viability differentiation reduce proinflammatory cytokines exert neuroprotective activity eliminating axonal loss vivo studies confirmed antidepressants delayed disease onset alleviated symptoms experimental autoimmune encephalomyelitis eae prevalent animal model ms antidepressant agents suppressed inflammation restrained demyelination decreasing immune cell infiltration cnsconclusion antidepressants efficient tackling numerous aspects disease pathophysiology vitro vivo models given several antidepressants already proved effective clinical trials ms patients inclusion agents therapeutic arsenal ms seriously considered following individualized approach minimize adverse events antidepressants ms patientspmid34093579 pmcpmc8173210 doi103389 fimmu2021677879,1.0
neurodegenerative diseases hotbed splicing defects potential therapies abstractprecursor messenger rna premrna splicing fundamental step eukaryotic gene expression systematically removes noncoding regions introns ligates coding regions exons continuous message mature mrna process highly regulated can highly flexible process known alternative splicing allows several transcripts arise single gene thereby greatly increasing genetic plasticity diversity proteome alternative splicing particularly prevalent neuronal cells splicing patterns continuously changing maintain cellular homeostasis promote neurogenesis migration synaptic function continuous changes splicing patterns high demand many cis transsplicing factors contribute susceptibility neuronal tissues splicing defects resultant neurodegenerative diseases large group disorders defined gradual loss neurons progressive impairment neuronal function several common neurodegenerative diseases involve form splicing defect s alzheimers disease parkinsons disease spinal muscular atrophy growing understanding rna splicing led explosion research field spliceswitching antisense oligonucleotide therapeutics review current understanding effects alternative splicing neuronal differentiation neuronal migration synaptic maturation regulation well impact neurodegenerative diseases will also review current landscape spliceswitching antisense oligonucleotides therapeutic strategy number common neurodegenerative disorders,0.0
parabacteroides produces acetate alleviate heparanaseexacerbated acute pancreatitis reducing neutrophil infiltration background endoglycosidase heparanase degrades heparan sulfate proteoglycans exerts proinflammatory mediator various inflammatory disorders however function underlying mechanism heparanase acute pancreatitis remain poorly understood investigated interplay heparanase gut microbiota development acute pancreatitismethodsacute pancreatitis induced wildtype heparanasetransgenic mice administration caerulein differences gut microbiota analyzed 16s ribosomal rna sequencing antibiotic cocktail experiment fecal microbiota transplantation cohousing experiments used assess role gut microbiotaresultsas compared wildtype mice acute pancreatitis exacerbated heparanasetransgenic mice moreover gut microbiota differed heparanasetransgenic wildtype mice heparanase exacerbated acute pancreatitis gut microbiotadependent manner specially commensal parabacteroides contributed distinguish differences wildtype heparanasetransgenic mice administration parabacteroides alleviated acute pancreatitis wildtype heparanasetransgenic mice addition parabacteroides produced acetate alleviate heparanaseexacerbated acute pancreatitis reducing neutrophil infiltrationconclusionsthe gutpancreas axis played important role development acute pancreatitis acetate produced parabacteroides may beneficial acute pancreatitis treatment video abstract,0.0
characterizing relapsing remitting multiple sclerosis patients burdened hypertension hyperlipidemia asthma abstractbackgroundhypertension hyperlipidemia asthma common multiple sclerosis ms patients adversely impact physical mental health independent sociodemographic clinical attributes characterizing ms patients comorbidities necessary informing comorbidity screening managed care vulnerable patient subgroups however sparse data currently availablemethodswe conducted crosssectional analyses 2 012 relapsing remitting rr ms patients separate multivariable logistic regression models conducted presence hypertension hyperlipidemia asthma independent variables included age sex race ms duration body mass index classification insurance payer smoking status median income residence zip code disease modifying therapies comorbiditiesresultshypertension common rrms patients older obese severely obese hyperlipidemia asthmatics living neighborhoods lowest income black americans rrms patients hyperlipidemia likely male older overweight obese severely obese hypertensive asthmatics white american asthmatic rrms patients likely female obese hypertensive living neighborhood medium low income less likely interferons glatiramer acetateconclusionwe identified factors independently associated common comorbidity burden rrms patients will inform riskstratification efforts aimed mitigating adverse impact conditions ms patients results consistent known determinants hypertension hyperlipidemia asthma nonms patient population therefore disparities exist screening management general us population may likely exist us ms patients also possible may unique differences specific ms patient subgroups warrants investigation detailed characterization,0.0
interactions among mtorc ampk sirt computational modelfor cell energybalance metabolism background cells adapt metabolism activities response signals surroundings ability essential survival face perturbations tissues deficit mechanisms commonly associated cellular aging diseases cardiovascular disease cancer immune system decline neurological pathologies several proteins identified able respond directly energy nutrient growth factor levels stress stimuli order mediate adaptations cell particular mtor ampk sirtuins known play essential role management metabolic stress energy balance mammalsmethodsto understand complex interactions signalling pathways environmental signals interactions may impact lifespan healthspan developed computational model metabolic signalling pathways specifically model includes insulin igf1 pathway couples energy nutrient abundance execution cell growth division ii mtorc1 amino acid sensors sestrin iii preisshandler salvage pathways regulate metabolism nad+ nad+ consuming factor sirt1 iv energy sensor ampk v transcription factors foxo pgc1resultsthe model simulates interactions among key regulators akt mtorc1 ampk nad+ sirt predicts dynamics key findings include clinically important role pras40 diet mtorc1 inhibition potential link sirt1activating compounds premature autophagy moreover model captures exquisite interactions leucine sestrin2 arginine resulting signal mtorc1 pathway results can leveraged development novel treatment cancers diseasesconclusionsthis study presents stateoftheart computational model investigating interactions among signaling pathways environmental stimuli growth ageing metabolism diseases model can used essential component simulate gene manipulation therapies eg rapamycin wortmannin calorie restrictions chronic stress assess functional implications longevity ageingrelated diseases video abstract,0.0
covid19 among patients multiple sclerosis systematic review neurol neuroimmunol neuroinflamm 2021 may 20 8 4 e1001 doi 101212 nxi0000000000001001 print 2021 julabstractobjective systematically reviewed literature covid19 patients multiple sclerosis ms methods searched pubmed scopus embase cinahl web science google scholar world health organization database december 1 2019 december 18 2020 three conference abstract databases also searched included types studies reported characteristics patients ms covid19results initial 2 679 publications 3 138 conference abstracts 87 studies 67 published articles 20 abstracts consisting 4 310 patients suspected confirmed covid19 ms met inclusion criteria female male ratio 2531 mean sd age 4491 431 years mean disease duration 1246 227 mean expanded disability status scale score 254 081 relapsing progressive ratio 4751 329 patients least 1 comorbidity common symptoms fever 688 followed cough 639 fatigue asthenia 512 shortness breath 395 total 837 4 043 patients ms suspected confirmed covid19 207 required hospitalization 130 4 310 30 died covid19 among suspected confirmed patients highest hospitalization mortality rates patients diseasemodifying therapies 429 84 followed b celldepleting agents 292 25 conclusion study suggested ms significantly increase mortality rate covid19 data interpreted caution patients ms likely female younger compared general population age male sex seem risk factors worse disease outcomepmid34016734 doi101212 nxi0000000000001001,0.0
calcineurin activity increased charcotmarietooth 1b demyelinating neuropathy schwann cells produce considerable amount lipids proteins form myelin pns reason quality control myelin proteins crucial ensure proper myelin synthesis deletion serine 63 p0 p0s63del protein myelin forming schwann cells causes charcotmarietooth type 1b neuropathy humans mice misfolded p0s63del accumulates er schwann cells elicits unfolded protein response upr perk upr transducer attenuates global translation reduces er stress phosphorylating translation initiation factor eif2alpha paradoxically perk ablation p0s63del schwann cells s63del perkscko reduced level peif2alpha leaving upr markers upregulated yet unexpectedly improved s63del myelin defects vivo therefore investigated hypothesis perk may interfere signals outside upr specifically calcineurin nfatc4 promyelinating pathway using mouse genetics including females males experimental setting show perk calcineurin interact p0s63del nerves calcineurin activity nfatc4 nuclear localization increased s63del schwann cells without altering egr2 krox20 expression moreover genetic manipulation calcineurin subunits appears either protective toxic s63del contextdependent manner suggesting schwann cells highly sensitive alterations calcineurin activitysignificance statement work shows novel activity function calcineurin schwann cells context er stress schwann cells expressing s63del mutation p0 protein induce unfolded protein response upregulate calcineurin activity calcineurin interacts er stress transducer perk relationship upr calcineurin schwann cells unclear propose protective role calcineurin s63del neuropathy although schwann cells appear sensitive regulation paper uncovers new important role calcineurin demyelinating diseases,1.0
infection mitigation strategies multiple sclerosis patients oral monoclonal diseasemodifying therapies curr neurol neurosci rep 2021 may 19 21 7 36 doi 101007 s1191002101117yabstractpurpose review newer higherefficacy diseasemodifying therapies dmts multiple sclerosis ms orals monoclonalshave profound immunomodulatory immunosuppressive properties older injectable therapies require risk mitigation strategies reduce risk serious infections review will provide systematic framework infectious risk mitigation strategies relevant therapiesrecent findings classify risk mitigation strategies according following framework 1 screening patient selection 2 vaccinations 3 antibiotic prophylaxis 4 laboratory mri monitoring 5 adjusting dose frequency dmt 6 behavioral modifications limit risk infection systematically apply framework infections risk mitigations available hepatitis b herpetic infections progressive multifocal leukoencephalopathy tuberculosis also discuss uptodate recommendations regarding covid19 vaccinations patients dmts offer practical comprehensive dmtspecific framework derisking strategies designed minimize risk infections associated newer ms therapiespmid34009478 doi101007 s1191002101117y,0.0
differential diagnosis vitritis adult patients ocul immunol inflamm 2021 may 18110 doi 101080 0927394820211898001 online ahead printabstractthe term vitritis refers presence cellular infiltration vitreous body usually context intraocular inflammation exclusively intermediate uveitis prominent cause vitritis including infectious autoimmune autoinflammatory etiologies corticosteroids immunosuppressive therapies started ruling infectious causes vitritis especially immunosuppressed individuals situations can mimic intermediate uveitis amyloidosis ocular tumors primary intraocular lymphoma always suspected case vitreous infiltrations individuals aged 50 yearspmid34003716 doi101080 0927394820211898001,0.0
insights relationship hippocampal connectivity memory performances early stage multiple sclerosis front neurol 2021 may 19 12667531 doi 103389 fneur2021667531 ecollection 2021abstractwhile memory impairment multiple sclerosis ms known associated hippocampal alterations whether hippocampal networks dynamically reorganize compensation mechanism still matter debate context aim identify patterns structural functional connectivity hippocampus rest brain possible relevance memory performances early ms thirtytwo patients first episode suggestive ms together 10 matched healthy controls prospectively explored baseline 1 5 years follow scanned mri underwent neuropsychological battery tests included selective reminding test brief visual memory test revised assess verbal visuospatial memory respectively hippocampal volume computed together four graph theory metrics study structural functional connectivity hippocampi rest brain associations network parameters memory performances assessed using linear mixedeffects lme models considering cognitive abilities verbal memory performances patients decreased time visuospatial memory performances maintained parallel hippocampal volumes decreased significantly structural functional connectivity metrics modified increase hippocampal connections time precisely modifications indicating reinforcement hippocampal shortdistance connections lme models revealed drop verbal memory performances associated hippocampal volume loss preservation visuospatial memory performances linked decreased hippocampal functional shortest path length conclusion demonstrated differential impairment memory performances early stages ms important interplay hippocampalrelated structural functional networks performances structural damage increases functional reorganization seems able maintain visuospatial memory performances strengthened shortdistance connectionspmid34093415 pmcpmc8170471 doi103389 fneur2021667531,0.0
snapshot neuronal dysfunction inflammation neuron 2021 may 19 109 10 17541754e1 doi 101016 jneuron202103005abstractneuronal function relies tightly controlled cytoskeleton transport adaptive cargo trafficking prerequisite synaptic transmission inflammation multiple sclerosis ms experimental autoimmune encephalomyelitis eae axonal transport efficiency declines followed neurodegeneration furthermore neuroinflammation causes imbalance excitatory inhibitory transmission triggering synaptic dysfunction loss recent data suggest neuronal transport synaptic deficits neuroinflammation functionally interconnected view snapshot open download pdfpmid34015268 doi101016 jneuron202103005,0.0
nutritional biochemical parameters among multiple sclerosis patients casecontrol study cureus 2021 may 19 13 5 e15108 doi 107759 cureus15108abstractbackground pathogenesis prognosis multiple sclerosis ms area active medical research dietary biochemical parameters serum 25dihydroxycholecalciferol magnesium potassium play role disease progression study aimed compare nutritional status biochemical profile patients without ms methodology casecontrol study included total 112 participants 56 control group 56 ms group participants socioeconomic demographic profiles nutritional status biochemical details gathered using history patient files records effect parameters presence ms evaluated using decision tree model students ttest mannwhitney u test performed compare parameters results decision tree model developed accuracy rate 8652 vitamin mineral intake groups showed significant statistical differences p 0001 differences important terms biochemical parameters especially serum levels 25dihydroxycholecalciferol potassium conclusions key parameters varied ms patients control group according constructed decision tree serum levels 25dihydroxycholecalciferol magnesium calcium potassium carbohydrate intake nutritional measures ms can taken based decision treepmid34155466 pmcpmc8211432 doi107759 cureus15108,0.0
recovery trajectories common musculoskeletal complaints diagnosis contra prognostic phenotypes background large variations symptoms prognostic factors among patients sharing musculoskeletal msk diagnosis making traditional diagnostic labelling helpful informing treatment prognosis recently identified five msk phenotypes across common msk pain locations latent class analysis lca aim study explore oneyear recovery trajectories pain functional limitations phenotypes describe relation course traditional diagnostic msk groupsmethodswe conducted longitudinal observational study 147 patients neck back shoulder complex pain primary health care physiotherapy data pain intensity function collected baseline week 0 1 2 3 4 6 8 12 26 52 weeks follow using webbased questionnaires mobile text messages recovery trajectories described separately traditional diagnostic msk groups based pain location patients categorized phenotype groups based prognostic factors shared among msk diagnostic groupsresultsthere general improvement function throughout year followup msk groups modest decrease pain intensity msk diagnoses dispersed across five phenotypes phenotypes showed clearly different trajectories recovery course symptoms 12 months followup variation captured single trajectory site specific msk diagnosesconclusionprognostic subgrouping revealed diverse patterns pain function recovery 1 year observed patients classified traditional diagnostic groups may better reflect diversity recovery common msk disorders,0.0
role folate microbiomelinked control autoimmunity j immunol res 2021 may 19 20219998200 doi 101155 2021 9998200 ecollection 2021abstractthe microbiome exerts considerable control immune homeostasis influences susceptibility autoimmune autoinflammatory disease ad aid inflammatory bowel disease ibd multiple sclerosis ms type 1 diabetes t1d psoriasis uveitis part due direct effects microbiome gastrointestinal gi physiology nutrient transport also indirect effects immunoregulatory controls including induction stabilization t regulatory cells t reg secreted bacterial metabolites shortchain fatty acids scfa intense investigation mediators effects contrast folate vitamin b9 essential micronutrient attracted less attention possibly exerts global physiological effects difficult differentiate specific effects immune system review role folate ad aid emphasis sightthreatening autoimmune uveitis since folate required generation maintenance t reg propose one mechanism microbiomebased control ad aid via folatedependent induction gi tract t reg particularly colonic t reg via anergic t cells t hence folate supplementation potential prophylactic therapeutic benefit aid adpmid34104654 pmcpmc8159645 doi101155 2021 9998200,0.0
cortical surface thickness subcortical volumes disability races relapsingremitting multiple sclerosis abstractbackgroundthe interplay cortical surface thickness cth subcortical volumes scv disability patients relapsing remitting multiple sclerosis rrms still clearobjectiveto examine relationship cth scv disability investigate differences cth scv disability african americans aa caucasian americans ca methodssixtyfive rrms 33aa 32 ca participants underwent expanded disability status scale multiple sclerosis functional composite msfc assessments including timed 25foot walk t25fw ninehole peg test 9hpt dominant d nondominant hand nd paced auditory serial addition test pasat3 symbol digit modalities test sdmt also administered participants underwent 3t brain mri cth measured frontal fa parietal pa temporal ta occipital oa cingulate ca global ga cortical surface areas csa scv measurements included thalamus tv caudate cv putamen pv pallidum pav hippocampus hv amygdala av accumbens acv brain stem bsv deep gray matter total volume dgmtv general linear model multivariate analysis manova used determine differences two cohorts spss vs 25 spearman rank correlation analysis performed investigate relationship cth msfcresultsaa significantly decreased fa pa ta ga cth compared ca p0004 p0018 p0013 p0015 respectively scv measurements significantly different ca msfc measures correlate significantly regional csa cth races entire group t25fw correlates tv pv av acv dgmtv p005 aa entire cohort pasat3 correlates tv acv p0041 p0006 p0006 p0000 respectively conclusionsdifferences csa cth reinforce different disease pathobiology aa ca regional cth may represent useful biomarker related multidomain disability ca aa dgm injury might important contributor disability longitudinal largescale studies warranted confirm findings,0.0
histone deacetylase 7 mediates endothelin1induced connective tissue growth factor expression human lung fibroblasts p300 activator protein1 activation background histone deacetylase hdac inhibition reported ameliorate lung fibrosis animal models however little known underlying mechanism hdac7 regulation ctgf production lung fibroblastsmethodsthe role hdac7 ctgf production caused et1 stimulation wi38 cells human lung fibroblast examined also evaluated expression hdac7 lung ovalbumininduced airway fibrosis model statistical data shown mean standard errorresultset1stimulated ctgf sma expression attenuated small interfering si rna interference hdac7 et1 promoted hdac7 translocation cytosol nucleus et1stimulated ctgf expression reduced transfection p300 sirna et1 induced increase p300 activity furthermore acetylation cjun timedependently induced et1 stimulation reduced transfection either hdac7 p300 sirna transfection hdac7 p300 sirna suppressed et1increased activity ap1luciferase moreover presence hdac7 required et1stimulated formation hdac7 p300 ap1 complex recruitment ctgf promoter region ovalbumininduced airway fibrosis model protein level hdac7 increased lung tissue distribution hdac7 colocalized smapositive cells subepithelial layer airwayconclusionset1 activates hdac7 initiate ap1 transcriptional activity recruiting p300 eventually promotes production ctgf hdac7 might play vital role airway fibrosis potential developed therapeutic target,0.0
activation gcn2 macrophages promotes white adipose tissue browning lipolysis leucine deprivation abstractwe previously shown leucine deprivation stimulates browning lipolysis white adipose tissue wat helps treat obesity adipose tissue macrophages atms significantly influence wat browning lipolysis however unclear whether atms involved leucine deprivationinduced browning lipolysis wat associated signals remain elucidated investigated role atms possible mechanisms involved wat browning lipolysis leucinedeprivation conditions study macrophages depleted mice injecting clodronateliposomes clod subcutaneous white adipose tissues mice lacking general control nonderepressible 2 kinase gcn2 sensor amino acid starvation specifically lyz2expressing cells generated investigate changes leucine deprivationinduced wat browning lipolysis found leucine deprivation decreased accumulation changed polarization atms ablation macrophages clod impaired wat browning lipolysis leucinedeprivation conditions mechanistically leucine deprivation activated gcn2 signals macrophages myeloidspecific abrogation gcn2 mice blocked leucine deprivationinduced browning lipolysis wat analyses revealed gcn2 activation macrophages reduced expression monoamine oxidase maoa resulting increased norepinephrine ne secretion macrophages adipocytes resulted enhanced wat browning lipolysis moreover injection cl316 243 3adrenergic receptor agonist inhibition maoa effectively increased level ne leading enhancement browning lipolysis wat myeloid gcn2 knockout mice leucine deprivation collectively results demonstrate novel function gcn2 signals macrophages regulating wat browning lipolysis leucine deprivation study provides important hints possible treatment obesity,0.0
claudin1 claudin3 molecular regulators myelination leukoaraiosis patients objectives leukoaraiosis described white matter lesions associated cognitive dysfunction neurodegenerative disorders etc myelin depletion salient pathological feature loss oligodendrocytes one robust alterations evident white matter degeneration recent studies revealed claudin proteins aberrantly expressed leukoaraiosis regulate oligodendrocyte activity however roles claudin1 claudin3 oligodendrocytes leukoaraiosis still welldefined methods quantitative polymerase chain reaction used measure expression claudin1 cldn1 claudin3 cldn3 myelinogenesisrelated genes myelin basic protein mbp proteolipid protein plp oligodendrocyte transcription factor 2 olig2 srybox transcription factor 10 sox10 leukoaraiosis patients n122 healthy controls n122 expression claudin1 claudin3 either ectopically silenced augmented olineu oligodendrocytes colony formation apoptosis migration assays performed finally expression myelin proteins evaluated western blotting results results revealed addition sox10 expression levels claudin1 claudin3 myelinogenesisrelated proteins prominently downregulated leukoaraiosis patients compared healthy controls furthermore growth migration olineu cells downregulated upon silencing claudin1 claudin3 however overexpression claudin1 claudin3 resulted reduction degree apoptosis olineu cells addition claudin1 claudin3 promoted expression mbp olig2 plp sox10 translational level conclusion data demonstrated abnormal expression claudin1 claudin3 regulates pathological progression leukoaraiosis governing viability myelination oligodendrocytes findings provide novel insights regulatory mechanisms underlying roles claudin1 claudin3 leukoaraiosis,1.0
lowered serum cesium levels schizophrenia association immuneinflammatory biomarkers cognitive impairments objectives previous study shown schizophrenia scz accompanied lowered levels trace metal elements including cesium however clear whether changes cesium rubidium rhenium associated activated immuneinflammatory pathways cognitive impairments symptomatology scz methods study measured cesium rubidium rhenium cognitive impairments using brief assessment cognition schizophrenia bacs levels cytokines chemokines interleukin il 1 tumor necrosis factor tnf eotaxin ccl11 120 patients scz 54 healthy controls severity illness assessed using brief psychiatric rating scale bprs scale assessment negative symptoms sans fibromyalgia chronic fatigue syndrome rating ff scale hamilton depression rating scale hamd results serum cesium significantly lower patients scz compared controls serum cesium significantly inversely associated ccl11 tnf il1 patients scz significant inverse associations also noted serum cesium levels bprs ff hamd sans scores finally cesium positively correlated neurocognitive probe results including tower london symbol coding controlled word association category instances digit sequencing task list learning tests conclusion results suggest lowered serum cesium levels may play role pathophysiology scz contributing specific symptom domains including negative depressive fatigue symptoms neurocognitive impairments spatial working episodic semantic memory executive functions neuroimmune pathways,0.0
influence equipment changes mri measures brain atrophy brain microstructure placebocontrolled trial ibudilast progressive multiple sclerosis mult scler j exp transl clin 2021 may 18 7 2 20552173211010843 doi 101177 20552173211010843 ecollection 2021 aprjunabstractbackground hardware changes can unavoidable confound imaging trials understanding impact changes may play important role analysis imaging dataobjective characterize effect equipment changes longitudinal multisite multiple sclerosis trialmethods using data clinical trial progressive multiple sclerosis explored major changes imaging hardware affected data analyzed extent changes affected imaging biomarkers estimated treatment effects including changes timedependent covariateresults significant differences whole brain atrophy brain parenchymal fraction bpf microstructure transverse diffusivity td scans without changes found depended type hardware change switch ge hdxt siemens skyra led significant shifts bpf p 004 td p 00001 however detect influence hardware changes overall trial outcomes differences placebo treatment arms change time bpf td p 05 conclusions results suggest differences among hardware types considered planning analyzing brain atrophy diffusivity longitudinal clinical trialpmid34046185 pmcpmc8138298 doi101177 20552173211010843,0.0
multiple sclerosis patients reduced resting increased activated cd4 + cd25 + foxp3 + t regulatory cells sci rep 2021 may 18 11 1 10476 doi 101038 s41598021884485abstractresting activated subpopulations cd4+cd25+cd127lot regulatory cells treg cd4+cd25+cd127+ effector t cells ms patients healthy individuals compared peripheral blood mononuclear cells isolated using ficoll hypaque stained monoclonal antibodies analysed flow cytometer cd45ra foxp3 expression within cd4+ cells cd4+cd25+cd127lot cells identified population cd45ra+foxp3+ population ii cd45rafoxp3hi population iii cd45rafoxp3+ cells effector cd4+cd127+ t cells subdivided population iv memory effector cd45ra cd25foxp3 population v effector nave cd45ra+cd25foxp3ccr7+ terminally differentiated ra+ temra effector memory cells chemokine receptor staining identified cxcr3+th1like treg ccr6+th17like treg ccr7+ resting treg resting treg population reduced ms patients untreated treated ms compared healthy donors activated memory treg population ii significantly increased ms patients compared healthy donors activated effector cd4+ population iv increased nave temra cd4+ population v decreased ms compared hd expression ccr7 mainly population whereas expression ccr6 cxcr3 greatest populations ii intermediate population iii ms ccr6+treg lower population iii study found ms associated significant shifts cd4+t cells subpopulations ms patients lower resting cd4+cd25+cd45ra+ccr7+ treg healthy donors activated cd4+cd25hicd45rafoxp3hitreg increased ms patients even treatment ms patients reduced ccr6+th17like treg may contribute activity mspmid34006899 doi101038 s41598021884485,0.0
advances drug development hepatocellular carcinoma clinical trials potential therapeutic targets abstractalthough hepatocellular carcinoma hcc one deadliest health burdens worldwide drugs available clinical treatment however recent years major breakthroughs made development new drugs due intensive fundamental research numerous clinical trials hcc traditional systemic therapy schemes emerging immunotherapy strategies advanced 2017 2020 united states food drug administration fda approved variety drugs treatment hcc including multikinase inhibitors regorafenib lenvatinib cabozantinib ramucirumab immune checkpoint inhibitors nivolumab pembrolizumab bevacizumab combined atezolizumab currently 1000 ongoing clinical trials involving hcc represents vibrant atmosphere hcc drug research development field additionally traditional chinese medicine approaches gradually optimized review summarizes fdaapproved agents hcc elucidates promising agents evaluated clinical phase ii iii trials identifies emerging targets hcc treatment addition introduce development hcc drugs china finally discuss potential problems hcc drug therapy possible future solutions indicate future directions development drugs hcc treatment,0.0
vista regulates microglia homeostasis myelin phagocytosis associated ms lesion pathology abstractvtype immunoglobulin domaincontaining suppressor tcell activation vista negative checkpoint regulator ncr involved tcell quiescence inhibition tcell activation myeloid cells regulates cytokine production chemotaxis phagocytosis tolerance induction central nervous system cns vista expressed microglia resident macrophage parenchyma expression decreased neuroinflammation however function vista microglia unknown extensively analyzed vista expression different ms lesion stages characterized function vista cns deleting vista microglia vista differentially expressed distinct ms lesion stages mice vista deletion cx3cr1expressing cells induced amoeboid microglia morphology indicating immuneactivated phenotype expression genes associated cell cycle immuneactivation increased vista ko microglia response lps experimental autoimmune encephalomyelitis eae vista ko wt microglia shared similar transcriptional profiles vista deletion affect eae disease progression microglia responses vista ko microglia vitro decreased uptake myelin study demonstrates vista involved microglia function likely affects healthy cns homeostasis neuroinflammation,1.0
dietary factors mri metrics early multiple sclerosis abstractbackgrounddespite significant interest diet ms community research topic limited published studies evaluating associations diet neuroimaging msmethodswe utilized baseline data radiems cohort early ms diagnosed 50 years n180 participants underwent brain mris derive normalized total gray thalamic volumes t2 lesion volume white matter microstructural integrity normal appearing white matter nawm participants completed food frequency questionnaires ffq calculated adherence scores prespecified dietary patterns including mediterraneandash intervention neurodegenerative delay mind diet evaluated intake following prespecified dietary components fruits vegetables legumes nuts whole grains dairy fried foods processed meats fat intake used multivariableadjusted linear regression evaluate mri metrics versus dietary measuresresultsmind diet score associated thalamic volume individuals highest quartile mind diet scores greater thalamic volumes versus lowest quartile q4 vs q1 103ml 95ci 026ml 179ml p001 individual food nutrients higher intakes fullfat dairy associated lower t2 lesion volumes q4 vs q1 093ml 95ci 151ml 035ml p001 higher intakes marine omega3 fatty acids associated greater nawm microstructural integrity q4 vs q1 040 95ci 003 076 p004 foods nutrients associated mri outcomesconclusionsin first study focused neuroimaging diet ms note significant associations crosssectional early ms cohort longitudinal followup imaging clinical outcomes will provide additional insights,0.0
melatonin multiple sclerosis melatonin nacetyl5methoxytryptamine neurohormone powerful antioxidant actions major effects relating immune system gastrointestinal tract sleepwake cycle involvement immunity led trials melatonin immunerelated diseases including rheumatoid arthritis systemic lupus erythematosus type 1 diabetes ankylosing spondylitis inflammatory bowel disease psoriasis fig 1 despite promising results animal models robust evidence benefit conditions zhao et al 2019 aug 1,0.0
teriflunomide relapsingremitting multiple sclerosis outcomes age pretreatment status ther adv neurol disord 2021 may 18 1417562864211005588 doi 101177 17562864211005588 ecollection 2021abstractbackground aims investigate effectiveness safety teriflunomide 14 mg daily association age pretreatment unselected ms patientsmethods prespecified analysis noninterventional prospective realworld study germanyresults total 558 495 patients 45 years old 593 patients 526 pretreated within 6 months prior teriflunomide baseline expanded disability status scale edss higher older age lower number relapses relapse rate decreased age groups treatmentnave 082 073 baseline 025 055 teriflunomide pretreated 048 076 022 050 patients 12 months compared year teriflunomide initiation edss remained stable patients age groups well therapynave pretreated patients 24 months percentage patients adverse events aes ranged 292 age group 2535 389 age group 5565 increased discontinuation rate commonly due diarrhoea alopecia nausea higher age groups ae rates lower pretreated compared treatmentnave patientsconclusion overall patients age groups including older patients irrespective pretreatment benefit teriflunomide treatment routine clinical practiceregistration bfarm public study database number 2075pmid34046085 pmcpmc8135216 doi101177 17562864211005588,0.0
emerging roles ccn3 protein immunerelated diseases mediators inflamm 2021 may 18 20215576059 doi 101155 2021 5576059 ecollection 2021abstractthe ccn proteins family extracellular matrix ecm associated proteins currently consist six secreted proteins ccn16 ccn3 protein also known nephroblastoma overexpressed protein nov member ccn family multiple biological functions implicated major cellular processes cell growth migration differentiation recently ccn3 emerged critical regulator variety diseases including immunerelated diseases including rheumatology arthritis osteoarthritis systemic sclerosis review will briefly introduce structure function ccn3 protein summarize roles ccn3 immunerelated diseases essential understand functions ccn3 immunerelated diseasespmid34393649 pmcpmc8356028 doi101155 2021 5576059,0.0
exosomes subjects multiple sclerosis express ebvderived proteins activate monocytederived macrophages neurol neuroimmunol neuroinflamm 2021 may 18 8 4 e1004 doi 101212 nxi0000000000001004 print 2021 julabstractobjective investigate crosssectional study effect serumderived exosomes primary human blood monocytederived macrophages mdms comparing exosomes healthy donors vs patients relapsingremitting multiple sclerosis remission relapse assess whether response correlates exosomal epsteinbarr virus ebv protein expressionmethods total 45 serumderived exosome preparations isolated patients healthy controls verified expression exosomal ebv markers mdms differentiated monocytes 7 days incubated 24 hours exosomes cell supernatants collected cytokine measurement cytometric bead array cells immunophenotyped differentiationresults serumderived exosomes patients multiple sclerosis ms expressed higher levels ebv proteins healthy controls interest expression ebv nuclear antigen ebna1 latent membrane proteins lmp1 2a higher exosomes derived patients active rrms compared healthy controls stable patients data normalization observed incubation ebv + exosomes induced cxcl10 ccl2 secretion mdms mdms differentiated patients active disease better secretors cxcl10 interferoninducible chemokines including ccl2 cxcl9 mdms healthy stable ms groups mdms active patients higher frequency cd14 ++ subset correlated secreted cxcl10conclusion exosomes expressing ebv proteins correlate disease activity induce inflammatory response mdms compounded origin responder cellspmid34006621 doi101212 nxi0000000000001004,0.0
impact ocrelizumab healthrelated quality life individuals multiple sclerosis mult scler j exp transl clin 2021 may 18 7 2 20552173211007523 doi 101177 20552173211007523 ecollection 2021 aprjunabstractbackground ocrelizumab approved treatment relapsing progressive multiple sclerosis ms objective examine impact ocrelizumab healthrelated quality life hrqol individuals msmethods ninetyeight individuals relapsing 32 progressive ms enrolled participants administered battery patientreported outcome pro measures first ocrelizumab infusion infusions 6 12 months pro measures included medical outcomes study sf36 neuroqolresults baseline participants low mean scores across hrqol domains 12 months increases observed sf36 rolephysical general health vitality roleemotional mental health mental component summary neuroqol improvements seen positive affect anxiety emotional behavioral dyscontrol fatigue several demographic clinical characteristics associated hrqol baseline strongest associations physical hrqol measures measures ms disability associations longitudinal change hrqol scores baseline demographic clinical characteristics mildconclusions observed significant improvements across multiple mental hrqol domains 12 months individuals treated ocrelizumab findings support use hrqol measures provide subjective measure treatment impact complements traditional outcomespmid34046184 pmcpmc8138295 doi101177 20552173211007523,0.0
intracranial complications immune checkpoint therapy patient nsclc multiple sclerosis case report jto clin res rep 2021 may 18 2 6 100183 doi 101016 jjtocrr2021100183 ecollection 2021 junabstractbackground immune checkpoint inhibitors icis become increasingly important tool cancer treatment revealing durable responses several different types tumors including nsclcs nevertheless icis carry risk immunemediated toxicities paucity data concurrent use agents patients autoimmune disorders multiple sclerosis ms case presentation report case man history ms metastatic nsclc brain metastases cancer progression receiving chemotherapy wholebrain radiation therapy stereotactic radiosurgery brain lesions treated programmed deathligand 1 inhibitor atezolizumab dramatic clinical radiographic benefit developed severe ms flare neurologic decline precluding treatment considerable growth previously radiated brain lesion prompted resection pathologic findings consistent radiation necrosis demyelination without viable tumor cellsconclusions although patients preexisting autoimmune diseases including ms might increased risk developing immunerelated adverse events icis may also experience anticancer benefit intracranial disease can challenging accurately diagnose patient ms previously underwent radiation progressing lesions can tumor growth ms flare radiation necrosispmid34590030 pmcpmc8474265 doi101016 jjtocrr2021100183,1.0
realworld outcomes complete nationwide cohort 3200 teriflunomidetreated multiple sclerosis patients danish multiple sclerosis registry plos one 2021 may 18 16 5 e0250820 doi 101371 journalpone0250820 ecollection 2021abstractobjective teriflunomide oncedaily oral diseasemodifying therapy dmt relapsing forms multiple sclerosis ms studied clinical outcomes realworld setting involving populationbased large cohort unselected patients enrolled danish multiple sclerosis registry dmsr started teriflunomide treatment 20132019methods complete nationwide populationbased cohort study prospectively enrolled unselected cases demographic diseasespecific patient parameters related treatment history efficacy outcomes discontinuation switching rates among clinical variables assessed baseline followup visitsresults total 3239 patients 654 female started treatment teriflunomide study period 56 treatmentnave compared previously treated patients treatmentnave patients older average disease onset shorter disease duration lower expanded disability status scale score teriflunomide treatment start frequently experienced relapse 12 months prior teriflunomide initiation 3001 patients initiating teriflunomide treatment least 12 months cutoff date 727 still treatment one year treatment start discontinuations first year due mainly adverse events 156 full followup period 475 patients discontinued teriflunomide treatment sixtythree percent patients treated teriflunomide 5 years relapsefree significantly treatmentnave versus previously treated patients experienced relapse followup p00001 furthermore 85 patients available data free disability worsening end followupconclusions solid efficacy treatment persistence data consistent realworld studies obtained treatment period treatment outcomes realworld scenario populationbased cohort support previous findings teriflunomide effective generally welltolerated dmt relapsing ms patients mild moderate disease activitypmid34003862 doi101371 journalpone0250820,0.0
modulation retinal atrophy rituximab multiple sclerosis neurology 2021 apr 7101212 wnl0000000000011933 doi 101212 wnl0000000000011933 online ahead printabstractobjective investigate effects rituximab retinal atrophy patients relapsingremitting multiple sclerosis rrms performed serial optical coherence tomography oct scans among cohort rrms patients rituximab compared rates ganglion cell+inner plexiform layer gcipl atrophy observed among age sexmatched glatiramer acetate ga natalizumabtreated rrms patients healthy controls hcs methods observational study patients rrms treated single diseasemodifying therapy hcs followed serial oct median duration 28 years participants uncontrolled hypertension diabetes mellitus glaucoma eyes optic neuritis 6 months prior baseline oct followup excluded statistical analyses performed using linear mixedeffects regressionresults overall followup period rates gcipl atrophy 028011m yr among rituximabtreated rrms patients n35 similar gatreated n49 033005m yr p069 natalizumabtreated patients n88 017010m yr p013 faster hcs n78 015003m yr p0006 rituximabtreated patients exhibited 055023m yr faster rates gcipl atrophy first 12 months treatment relative afterwards n25 p002 period gcipl atrophy rates 014013m yrconclusions retinal atrophy rrms modulated rituximab greater attenuation retinal atrophy may occur 12 months rituximab treatment following time gcipl atrophy rates similar observed among natalizumabtreated rrms patients hcs findings raise possibility neuroprotective therapeutic response rituximab rrms may take 12 months though confirmed larger studiesclassification evidence study provides class iv evidence difference rate change ganglion cell+inner plexiform layer thickness patients rrms comparing rituximab dmtspmid33827962 doi101212 wnl0000000000011933,1.0
clinicoradiologic features therapeutic strategies tumefactive demyelination retrospective analysis 50 consecutive cases ther adv neurol disord 2021 may 18 1417562864211006503 doi 101177 17562864211006503 ecollection 2021abstractaims goal expand spectrum clinicoradiologic characteristics possible therapeutic choices patients tumefactive demyelinating lesions tdls methods retrospective analysis 50 patients least one tdl performed academic neurology center 20082020 results cohort comprised mostly women 33 50 mean age 38 years tdl onset mean followup time 76 months mean expanded disability status scale score tdl onset latest neurological evaluation 37 23 respectively subcategorized patients seven groups based mainly clinical radiological findings disease course group included patients presenting marburglike tdl n 4 groups b c comprised patients presenting monophasic n 7 recurrent tdls n 12 respectively multiple sclerosis ms patients subsequently developed tdl n 16 disease course categorized group d group e comprised patients initially presented tdl subsequently developed classical relapsingremitting ms without evidence tdl n 5 groups f n 2 g n 4 involved ms patients developed tdl drug initiation natalizumab fingolimod cessation interferon fingolimod respectively regarding longterm treatments applied corticosteroid administration acute phase bcelldirected therapies shown highly effective especially cases recurrent tdls cyclophosphamide spared aggressive disease indicated poor response corticosteroids plasma exchange failureconclusion tumefactive central nervous system demyelination heterogenous disease stratification distinct groups according different phenotypes can establish efficient treatment strategies thus improving clinical outcomes futurepmid34046086 pmcpmc8135218 doi101177 17562864211006503,1.0
bortezomib antinmdar encephalitis following daclizumab treatment patient multiple sclerosis bmj neurol open 2021 may 18 3 1 e000096 doi 101136 bmjno2020000096 ecollection 2021abstractbackground daclizumab anticd25 monoclonal antibody developed treatment relapsing remitting multiple sclerosis withdrawn worldwide march 2018 due emerging serious immunemediated systemic andcentral nervous system adverse events report case antinmethyldaspartate receptor nmdar encephalitis occurring 14 weeks stopping daclizumab responded proteasome inhibitor bortezomibmethods following lack effective clinical response first line corticosteroid plasma exchange intravenous immunoglobulin second line rituximab treatments bortezomib therapy commenced patient received six cycles bortezomib treatmentresults clinical improvement noted 4 weeks first six cycles bortezomib patient experienced sustained clinical improvementconclusion case provides class iv evidence use bortezomib therapy treatment refractory antinmdar encephalitispmid34079936 pmcpmc8137234 doi101136 bmjno2020000096,0.0
realworld experience ocrelizumab initiation diverse multiple sclerosis population abstractbackgroundocrelizumab ocr humanized monoclonal antibody directed cd20 positive blymphocytes approved use 2017 us food drug administration fda relapsingremitting primary progressive forms multiple sclerosis ms objectiveto provide realworld data patients ms treated ocr center evaluate safety efficacy across different ethnic groups studied previous clinical trialsmethodswe performed retrospective observational analysis ms patients treated ocr march 31 2017 april 30 2020 collected data patients received least one dose infusion ocr ms center patient characteristics including demographics clinical disease course documented side effects collected analyzedresultsa total 82 patients eligible study 72 relapsingremitting ms rrms 14 primary progressive ms ppms 11 active relapsing secondary progressive ms spms 22 patients african american descent 61 caucasian 17 hispanic descent mean age starting ocr 4111 years 47 treatment nave started ocr 24 previously treated one diseasemodifying therapy dmt 14 treated two dmts 15 treated two dmts prior ocr 50 patients least one adverse event ocr 48 adverse events requiring ocr discontinuation 36 infusionrelated reactions 73 viral infections found two cases severe babesiosis along index cases reactivation lichen planus agranulocytosis severe lymphopenia ectopic pregnancy cases malignancy progressive multifocal leukoencephalopathy death within cohort mean time ocr initiation 173 months rrms group 222 months ppms group 282 months spms group annualized relapse rate reduced 133 015 rrms group mean extended disability status scale edss scores worsen across ms phenotypes ethnic groups treated ocrconclusionsin diverse patient population ocr welltolerated without significant adverse events novel cases severe babesiosis reactivation lichen planus lymphopenia agranulocytosis ectopic pregnancy vital consider geographic risk factors may expose patients babesia microti b microti either considering initiating ocr therapy additional six cases severe b microti cases associated ocr reported fda adverse event reporting system faers along multiple babesiosis cases associated dmts including rituximab ocr found cohort effective decreasing relapse rates maintaining edss scores study extends generalizability ocr clinical trials realworld setting consisting diverse population,0.0
hydroxycarboxylic acid receptor 2 pleiotropically linked receptor multiple sclerosis drug monomethyl fumarate possible implications inflammatory response front immunol 2021 may 18 12655212 doi 103389 fimmu2021655212 ecollection 2021abstractmonomethyl fumarate mmf metabolite dimethyl fumarate dmf immunosuppressive drug approved treatment multiple sclerosis ms potent agonist hydroxycarboxylic acid receptor 2 hcar2 eliciting signals dampen cell activation lead inflammation skin flushing reaction one main side effects treatment together gastrointestinal inflammation aim understand molecular basis underlying differential effects drug used wildtype hcar2 knockout mice investigate vitro ex vivo steadystate pathological conditions hcar2mediated signaling pathways activated mmf dendritic cells dc promote differentiation t cells intestinal epithelial cells iec activation proinflammatory pathway cyclooxygenase2 pathway involved skin flushing underlie gastrointestinal side effects drug understand dmf treatment might impact gut inflammation induced experimental autoimmune encephalomyelitis eae animal model ms used 3d xray phase contrast tomography flow cytometry monitor possible intestinal alterations morphological immunological levels respectively show hcar2 pleiotropically linked receptor mmf mediating activation different pathways leading different outcomes different cell types depending experimental invitro invivo conditions small intestine eaeaffected mice dmf treatment affected migration tolerogenic dc lamina propria mesenteric lymph nodes reverted profile proinflammatory probably result reduced expression aldehyde dehydrogenase transforming growth factor beta well inflammatory environment nevertheless dmf treatment amplify morphological alterations induced eae basis understanding mmf signaling hcar2 suggest pleiotropic signaling fumarate via hcar2 addressed pharmaceutical relevance devising new lead compounds reduced inflammatory side effectspmid34084164 pmcpmc8167049 doi103389 fimmu2021655212,0.0
relationship symptoms stage change adopting healthy life style quality life patients liver cirrhosis crosssectional study background previous studies patients liver cirrhosis considered broad range symptoms association healthy behavior quality life purposes study examine association symptoms adopting exercise consuming fruits vegetables identify factors associated quality life patients liver cirrhosismethodsthis crosssectional study enrolled 91 consecutive patients liver cirrhosis one tertiary general hospital south korea february 2016 january 2017 study participant completed selfadministered questionnaire measured symptom stage change engaging exercise consumption fruits vegetables korean version 36item shortform health survey multivariate ordinal logistic regression analysis multiple regression models used respectively examine association symptom stage change engaging exercise consumption fruits vegetables evaluate factors affecting quality liferesultsexperiencing nausea associated readiness change engaging exercise experiencing shortness breath associated less readiness change engaging exercise experiencing right upper quadrant pain associated readiness change engaging consumption fruits vegetables muscle cramps anorexia right upper quadrant pain body pain itching ascites edema bruising change appearance negatively affected quality lifeconclusionsthe results suggest types symptoms experienced patient liver cirrhosis hinder promote patients adoption exercise dietary behavior experiencing symptoms may negatively affect quality life caregivers provide supportive care patients liver cirrhosis includes assessing managing symptoms improve quality life,0.0
experience covid19 astrazeneca vaccination people multiple sclerosis abstractbackgroundsome people multiple sclerosis pwms increased risk severe coronavirus disease 19 covid19 rapidly vaccinated however vaccine supplies limited concerns sideeffects particularly chadox1ncov19 astrazeneca vaccineobjectivesto report first experience pwms receiving astrazeneca vaccinemethodsservice evaluation pwms using ms service barts health nhs trust sent questionnaires report symptoms following vaccinationresultsthirtythree responses returned 29 33 pwms received first dose astrazeneca vaccine remaining four received first dose biontech pfizer vaccineall two patients 94 reported symptoms including sore arm 70 flulike symptoms 64 fever 21 fatigue 27 headache 21 2 3 patients symptoms lasted 48 hours exception two pwms reporting symptom duration 10 12 days respectively symptoms remainder resolved within seven days severe adverse effects occurredconclusionspwms report transient symptoms following astrazeneca vaccination characteristics similar reported nonms population symptoms may pronounced pwms due temperaturedependent delay impulse propagation uhthoffnulls phenomenon due demyelination,1.0
can systemic anticd20 b celldepleting antibodies eliminate meningeal follicles multiple sclerosis neurol neuroimmunol neuroinflamm 2021 may 17 8 4 e1000 doi 101212 nxi0000000000001000 print 2021 julno abstractpmid34001659 doi101212 nxi0000000000001000,0.0
therapeutic opportunities interleukin33 central nervous system front immunol 2021 may 17 12654626 doi 103389 fimmu2021654626 ecollection 2021abstractinterleukin33 il33 member il1 cytokine family involved various diseases il33 exerts effects via heterodimeric receptor complex comprises suppression tumorigenicity 2 st2 il1 receptor accessory protein il1rap increasing evidence demonstrated il33 st2 signaling plays diverse crucial roles homeostasis central nervous system cns pathogenesis cns diseases including neurodegenerative diseases cerebrovascular diseases infection trauma ischemic stroke current review focus functional roles cellular signaling mechanisms il33 cns evaluate potential diagnostic therapeutic applicationspmid34079543 pmcpmc8165230 doi103389 fimmu2021654626,0.0
genetic inactivation sarm1 axon degeneration pathway improves outcome trajectory experimental traumatic brain injury based pathological radiological functional measures abstracttraumatic brain injury tbi causes chronic symptoms increased risk neurodegeneration axons white matter tracts corpus callosum cc critical components neural circuits particularly vulnerable tbi treatments needed protect axons traumatic injury mitigate posttraumatic neurodegeneration sarm1 protein central driver axon degeneration conserved molecular pathway sarm1 mice knockout ko sarm1 gene enable genetic proofofconcept testing sarm1 pathway therapeutic target evaluated sarm1 deletion effects tbi using concussive model causes traumatic axonal injury progresses cc atrophy 10 weeks indicating posttraumatic neurodegeneration sarm1 wildtype wt mice developed significant cc atrophy reduced sarm1 ko mice ultrastructural classification pathology individual axons using electron microscopy demonstrated sarm1 ko preserved intact axons reduced damaged demyelinated axons longitudinal mri studies live mice identified significantly reduced cc volume tbi sarm1 wt mice attenuated sarm1 ko mice mr diffusion tensor imaging detected reduced fractional anisotropy genotypes axial diffusivity remained higher sarm1 ko mice immunohistochemistry revealed significant attenuation cc atrophy myelin loss neuroinflammation sarm1 ko mice tbi functionally sarm1 ko mice exhibited beneficial effects motor learning sleep behavior based findings sarm1 inactivation can protect axons white matter tracts improve translational outcomes associated cc atrophy posttraumatic neurodegeneration,1.0
spectral characterization antioxidant antimicrobial cytotoxic cyclooxygenase inhibitory activities aloysia citriodora essential oils collected two palestinian regions background aloysia citriodora palau ac commonly known lemon verbena utilized medicinal tea folkloric medicine treatment abdominal spasm anxiety fever present investigation aimed identify chemical ingredients ac essential oil eo collected two different locations palestine assess antioxidant antimicrobial cytotoxic cyclooxygenase cox inhibitory effectsmethodsgas chromatography mass spectroscopy gc ms technique used identify chemical components hydrodistilled eo regions dpph mts cox assays utilized estimate antioxidant cytotoxic cox inhibitory activities eos respectively moreover broth microdilution assay used assess antimicrobial potentials seven microbial strainsresultsthe gc ms technique revealed presence 17 compounds ac collected umm alfahm region 13 compounds sample baqa algharbiyye region citral major component eos representing 4762 4346 respectively baqa algharbiyye ac eo exerted potent antioxidant activity umm alfahm eo ic50 values 1174 018 3548 014 g ml respectively positive control trolox antioxidant ic50 values 245 001 g ml interestingly eos inhibited potential activity methicillinresistant staphylococcus aureus mrsa proteus vulgaris ciprofloxacin ampicillin antibiotics also showed potent antifungal activity candida albicans fluconazole moreover baqa algharbiyye ac eo potent cytotoxic effect umm alfahm eo ic50 values 845 024 3331 001 g ml respectively compared doxorubicin ic50 dose 2201 14 g ml eos baqa algharbiyye showed potent activity cox1 cox2 enzymes ic50 5293 013 8931 021 g ml respectively eos umm alfahm region showed weaker activity enzymes ic50 34999 033 132637 113 g ml respectivelyconclusionboth characterized eos huge variety chemical components baqa algharbiyye ac eo potent antioxidant cytotoxic activities umm alfahm eo potential antimicrobial activity mrsa p vulgaris c albicans results suggest use ac eos promising sources active ingredients food cosmetic pharmaceutical industries,0.0
causal relationship ca3 backprojection dentate gyrus role ca1 fast ripple generation background pathophysiological evidence temporal lobe epilepsy models highlights hippocampus affected structure due high degree neuroplasticity control dynamics limbic structures necessary encode information conferring intrinsic epileptogenicity loss control results observable oscillatory perturbations called fast ripples epileptic rats events found ca1 ca3 dentate gyrus dg principal regions trisynaptic circuit hippocampus present work used granger causality address relationships among three regions trisynaptic circuit needed cause fast ripples ca1 vivo model purposes male wistar rats 210300 g injected single dose pilocarpine hydrochloride 24 mg 2 l right lateral ventricle videomonitored 24 h day detect spontaneous recurrent seizures detected rats implanted microelectrodes regions fixedrecording tungsten wire electrodes 60m outer diameter ipsilateral pilocarpine injection total 336 fast ripples recorded probabilistically characterized fast ripples made subset fast ripple events associated sharpwaves ca1 region n 40 analyze granger causalityresultsour results support existing evidence vitro fast ripple events ca1 initiated ca3 multiunit activity describe general synchronization theta band across three regions analyzed dg ca3 ca1 just fast ripple event ca1 begunconclusionthis vivo study highlights causal participation ca3 backprojection dg connection commonly overlooked trisynaptic circuit facilitator closedloop among regions prolongs excitatory activity ca3 speculate loss inhibitory drive dg mechanisms ripplerelated memory consolidation also ca3 backprojection dg fundamental role might underlying processes fast ripples generation ca1,0.0
relapses add permanent disability relapsing multiple sclerosis patients abstractobjectivewhether relapses direct effects permanent disability multiple sclerosis still unsettled issue aimed investigating cumulative effect breakthrough relapses expanded disability status scale edss relapsingonset ms patients disease modifying therapy dmt methodsfrom danish multiple sclerosis registry identified patients denmark relapsingonset ms started dmt followed first day treatment included patients aged 1859 kurtzkenulls edss score 60 entry compared patients without relapses followup endpoints 1 annualized increase edss 2 time 6month sustained edssworsening 3 time edss 60 4 time increase pyramidal cerebellar functional systems patients without relapses entry 11 matched sex edss age entry analysed edssworsening adjusted generalized linear models time endpoints adjusted cox regressionresultswe included 1 428 patients breakthrough relapses 1 428 without adjusted annualized increase edss 0179 patients relapses 95 ci 0164 9194 0086 patients without relapses 95 ci 0074 0097 patients edss 40 entry difference hazard ratio irreversible worsening edss 183 95 ci 158 212 irreversible increase edss 60 162 95 ci 125 210 irreversible increase pyramidal cerebellar functional system scores also happened significantly earlier patients breakthrough relapsesconclusionsour results indicate breakthrough relapses dmt associated increasing permanent disability patients edss 40 treatment start calls effective prevention relapses,0.0
different doses fingolimod relapsingremitting multiple sclerosis systematic review metaanalysis randomized controlled trials front pharmacol 2021 may 17 12621856 doi 103389 fphar2021621856 ecollection 2021abstractbackground efficacy safety fingolimod relapsingremitting multiple sclerosis rrms well verified several large randomized controlled trials rcts past decade however fewer systematic comparisons different doses fingolimod whether dose 05 mg d optimal one still remains solved objective objective systematic review evaluate efficacy safety four existing doses fingolimod treatment rrms especially dose 05 mg d methods medline embase cochrane library clinicaltrialsgov searched rcts performed evaluate different doses fingolimod corresponding control placebo dmts october 2020 review manager 53 software used assess data risk ratio rr mean difference md analyzed calculated random effect model results pooled 7184 patients 11 rcts fingolimod 05 mg d superior control group eight efficacy outcomes including annualized relapse rate arr md 022 95ci 029 014 p 000001 surprisingly showed higher risk basalcell carcinoma rr 440 95ci 158 1224 p 0004 although 125 mg d twice dose 05 mg d effect size almost similar dose 5 mg d obtained unsatisfactory efficacy showing greater risk adverse events three doses rr 117 95ci 105 130 p 0003 additionally fingolimod 025 mg d showed better performance delaying disease progress magnetic resonance imaging mri also achieved certain degree patient treatment satisfaction conclusion present 05 mg d remains optimal dose fingolimod rrms patients trials lower dose still great clinical significance paid attentionspmid34079453 pmcpmc8165387 doi103389 fphar2021621856,0.0
omopcdm based pharmacovigilance dataprocessing pipeline pdp providing active surveillance adr signal detection realworld data sources background adverse drug reactions adrs regarded major cause death major contributor public health costs active surveillance drug safety use realworld data realworld evidence part overall pharmacovigilance process important regard many studies apply datadriven approaches support pharmacovigilance developed pharmacovigilance dataprocessing pipeline pdp utilized electronic health records ehr spontaneous reporting system srs data explore pharmacovigilance signalsmethodsto end integrated two medical data sources konyang university hospital kyuh ehr united states food drug administration fda adverse event reporting system faers part presented pdp converted ehr data observation medical outcomes partnership omop data model evaluate ability using proposed pdp pharmacovigilance purposes performed statistical validation using drugs induce ear disordersresultsto validate presented pdp extracted six drugs ehr significantly involved adrs causing ear disorders nortriptyline hazard ratio hr 806 95 ci 2412691 metoclopramide hr 335 95 ci 301374 doxycycline hr 173 95 ci 114262 digoxin hr 160 95 ci 108238 acetaminophen hr 159 95 ci 147172 sucralfate hr 121 95 ci 106138 faers strongest associations found nortriptyline reporting odds ratio ror 194 95 ci 173216 sucralfate ror 122 95 ci 101145 doxycycline ror 130 95 ci 120140 hydroxyzine ror 117 95 ci 106129 confirmed results metaanalysis using random fixed models doxycycline hydroxyzine metoclopramide nortriptyline sucralfateconclusionsthe proposed pdp support active surveillance strengthening potential adr signals via realworld data sources addition pdp able generate realworld evidence drug safety,0.0
therapy pediatriconset multiple sclerosis state art challenges opportunities front neurol 2021 may 17 12676095 doi 103389 fneur2021676095 ecollection 2021abstracttreatment pediatriconset multiple sclerosis poms tailored observational studies data obtained clinical trials adultonset multiple sclerosis aoms patients increasing number new therapeutic agents aoms many will formally studied use also poms however important efficacy safety concerns regarding use therapies children young adults review will discuss current state art poms therapy will focus newer therapies oral infusion diseasemodifying drugs still currently investigationpmid34079516 pmcpmc8165183 doi103389 fneur2021676095,0.0
synthesis 15n nmr signal amplification reversible exchange 15n dalfampridine microtesla magnetic fields chemphyschem 2021 mar 18 doi 101002 cphc202100109 online ahead printabstractsignal amplification reversible exchange sabre technique enables nuclear spin hyperpolarization wide range compounds using parahydrogen present synthetic approach prepare 15 nlabeled 15 n dalfampridine 4amino 15 n pyridine utilized drug reduce symptoms multiple sclerosis synthesized compound hyperpolarized using sabre microtesla magnetic fields sabresheath technique 20 15 n polarization 7hourlong activation sabre precatalyst ir imes cod cl presence 15 n dalfampridine can remedied use pyridine coligand catalyst activation retaining 15 n polarization levels 15 n dalfampridine effects experimental conditions polarization transfer magnetic field temperature concentration parahydrogen flow rate pressure 15 n polarization levels free equatorial catalystbound 15 n dalfampridine investigated moreover studied 15 n polarization buildup decay magnetic field less 004 t well 15 n polarization decay earths magnetic field 14 tpmid33738893 doi101002 cphc202100109,0.0
nefm dna methylation correlates immune infiltration survival breast cancer background study aims determine whether nefm neurofilament medium dna methylation correlates immune infiltration prognosis breast cancer brca explore nefmconnected immune gene signaturemethodsnefm transcriptional expression analyzed brca normal breast tissues using oncomine tumor immune estimation resource timer databases relationship nefm dna methylation nefm transcriptional expression investigated tcga potential influence nefm dna methylation expression clinical outcome evaluated using tcga brca human protein atlas kaplanmeier plotter databases association nefm transcriptional expression dna methylation cancer immune infiltration investigated using timer tisidb databasesresultshigh expression nefm correlated better overall survival os recurrencefree survival rfs tcga brca kaplanmeier plotter whereas nefm dna methylation worse os tcga brca nefm transcriptional expression negatively correlated dna methylation nefm dna methylation significantly negatively correlated infiltrating levels b cd8+ t cd4+ t cells macrophages neutrophils dendritic cells timer tisidb nefm expression positively correlated macrophage infiltration timer tisidb adjusted tumor purity nefm expression weekly negatively correlated infiltration level b cells whereas positively correlated cd8+ t cell infiltration timer gene modules nefm expression dna methylation correlated diverse immune markers tcga tisidbconclusionsnefm lowexpression dna methylation correlates poor prognosis nefm expression positively correlates macrophage infiltration nefm dna methylation strongly negatively correlates immune infiltration brca study highlights novel potential functions nefm expression dna methylation regulation tumor immune microenvironment,0.0
tissuespecific transcriptome analyses reveal candidate genes stilbene flavonoid anthraquinone biosynthesis medicinal plant polygonum cuspidatum background polygonum cuspidatum sieb et zucc wellknown medicinal plant whose pharmacological effects derive mainly stilbenes anthraquinones flavonoids compounds accumulate differentially root stem leaf however molecular basis tissuespecific accumulation remains poorly understood tissuespecific accumulation compounds usually associated tissuespecific expression related biosynthetic enzyme genes regulators aimed clarify compare transcripts expressed different tissues p cuspidatum studyresultshighthroughput rna sequencing performed using three different tissues leaf stem root p cuspidatum total 80 981 unigenes obtained 40 729 annotated 21 235 differentially expressed genes identified fiftyfour candidate synthetase genes 12 transcription factors associated stilbene flavonoid anthraquinone biosynthetic pathways identified expression levels three different tissues analyzed phylogenetic analysis polyketide synthase gene families revealed two novel chs genes p cuspidatum phenylpropanoid pathway genes predominantly expressed root stem methylerythritol 4phosphate isochorismate pathways anthraquinone biosynthesis dominant leaf expression patterns synthase genes almost accordance metabolite profiling different tissues p cuspidatum measured highperformance liquid chromatography ultraviolet spectrophotometry predicted transcription factors associated regulation phenylpropanoid pathway expressed lower levels stem leaf root consistent trend expression observed leaf rootconclusionsthe molecular knowledge key genes involved biosynthesis p cuspidatum stilbenes flavonoids anthraquinones poor study offers novel insights biosynthetic regulation bioactive compounds different p cuspidatum tissues provides valuable resources potential metabolic engineering important medicinal plant,0.0
serum levels mir215p mir3395p associate occupational trichloroethylene hypersensitivity syndrome background trichloroethylene tce hypersensitivity syndrome ths doseindependent potentially lifethreatening disease study sought identify thsrelated mirnas evaluate potential clinical valuemethodsserum samples five patients five matched tce contacts used screening differential mirnas another 34 patients 34 matched tce contacts used verifying significantly differential mirnas sybr green pcr mgb pcr diagnostic model based mirnas established via support vector machine svm algorithm correlation differential mirnas liver function analyzed via spearman correlation testresultsa total 69 mirnas found differentially expressed mir215p mir3395p verified significant higher expressions patients sensitivity specificity accuracy disease model 100 75 86 respectively two mirnas showed significant correlations liver functionconclusionthese findings suggested mirnas profiles serum ths patients changed significantly mir215p mir3395p associated ths,0.0
higher cd19+cd25+ bregs independently associated better graft function renal transplant recipients background identification b cell subsets regulatory functions might open way new therapeutic strategies field transplantation aim reduce dose immunosuppressive drugs prolong graft survival cd25 proposed marker bcell subset immunosuppressive action termed bregs effect cd19 + cd25 + bregs graft function renal transplant recipients yet elucidated investigated potential impact cd19 + cd25 + bregs renal graft function well possible interaction cd19 + cd25 + bregs peripheral tregs healthy controls endstage kidney disease patients eskd renal transplant recipients moreover aimed investigate association cd19 + cd25 + bregs serum il10 tgf1 ifn study groupsmethodthirtyone healthy controls ninety renal transplant recipients eighteen eskd patients enrolled evaluated cd19 + cd25 + bregs treg absolute counts next investigated cd19 + cd25 + bregs predictors good graft function multiple regression roc analyses finally evaluated association cd19 + cd25+ bregs serum il10 tgf ifnresultseskd patients renal transplant recipients showed lower counts cd19 + cd25+ bregs compared healthy controls p 0001 higher cd19 + cd25+ breg counts independently associated better gfr renal transplant recipients unstandardized b coefficient 9 p 002 patients higher cd19 + cd25+ bregs independently associated higher treg counts unstandardized b 28 p 0004 roc analysis cutoffs cd19 + cd25 + breg counts serum tgf1 012 cell l 19 6354 pg ml respectively shown provide good sensitivity specificity identifying gfr 30 ml min auc 067 sensitivity 77 specificity 43 auc 065 sensitivity 81 specificity 50 respectively finally significant positive association cd19 + cd25+ bregs tgf1 shown renal transplant recipients r 0255 p 0015 conclusionsour findings indicate higher counts cd19 + cd25+ bregs independently associated better renal function higher absolute treg counts renal transplant recipients,0.0
exposure breastfeeding risk developing multiple sclerosis int j epidemiol 2021 may 17 50 2 644651 doi 101093 ije dyaa250abstractbackground earlylife factors reported modulate risk developing multiple sclerosis ms among adults association exposure breastfeeding risk ms debated aimed disclose whether past exposure breastfeeding duration associated risk developing msmethods used cohort design linking prospectively collected information breastfeeding cohort norway communitybased surveys health status conor norwegian ms registry populationbased medical birth registry norway includes information births norway since 1967 ms clinical onset collected throughout 2016 total 95 891 offspring born 1922 1986 mothers participating conor included identified 215 offspring within cohort developed adultonset ms associations breastfeeding ms risk estimated hazard ratios using cox proportional hazard models adjusting maternal factors including educationresults found association breastfed 4 months ms risk also adjusting various maternal factors hazard ratio 090 95 confidence interval 068119 estimates change different durations breastfeeding results similar adjusting perinatal factorsconclusion study confirm previous findings association breastfeeding risk ms breastfeeding information less likely biased knowledge disease compared casecontrol studiespmid34000734 doi101093 ije dyaa250,0.0
methodology dccss later fatigue study model investigate chronic fatigue longterm survivors childhood cancer background debilitating late effect childhood cancer survivors ccs cancerrelated fatigue crf little known prevalence risk factors fatigue population describe methodology dutch childhood cancer survivor late effect study fatigue dccss later fatigue study aim dccss later fatigue study examine prevalence factors associated crf proposing model discerns predisposing triggering maintaining moderating factors triggering factors related cancer diagnosis treatment childhood thought trigger fatigue symptoms maintaining factors daily life psychosocial factors may perpetuate fatigue triggered moderating factors might influence way fatigue symptoms express individuals predisposing factors already existed diagnosis genetic factors thought increase vulnerability develop fatigue methodology participant inclusion data collection planned analyses dccss later fatigue study presentedresultsdata 1955 ccs 455 siblings collected analysis data planned aim start reporting first results 2022conclusionthe dccss later fatigue study will provide information epidemiology crf investigate role broad range associated factors ccs insight associated factors fatigue survivors experiencing severe persistent fatigue may help identify individuals risk developing crf may aid development interventions,0.0
complete spatial characterisation nglycosylation upon striatal neuroinflammation rodent brain background neuroinflammation underlying pathology neurological conditions understanding still comprehended specific molecular pathway overlooked neuroinflammation glycosylation ie posttranslational addition glycans protein structure nglycosylation specific type glycosylation cardinal role central nervous system cns highlighted congenital glycosylation diseases result neuropathological symptoms epilepsy mental retardation changes nglycosylation can ultimately affect glycoproteins functions will impact cell machinery therefore characterisation nglycosylation alterations neuroinflammatory scenario can provide potential target future therapiesmethodswith aim unilateral intrastriatal injection lipopolysaccharide lps adult rat brain used model neuroinflammation vivo postmortem quantitative spatial characterisation neuroinflammation nglycome performed 1week postinjection lps aspects investigated multifaceted approach based positron emission tomography pet quantitative histology reverse transcriptionquantitative polymerase chain reaction rtqpcr liquid chromatography matrixassisted laser desorption ionisation mass spectrometry imaging maldimsi resultsin brain region showing lpsinduced neuroinflammation significant decrease abundance sialylated core fucosylated structures seen approximately 75 85 respectively whereas oligomannose nglycans significantly increased 135 confirmed maldimsi provided highresolution spatial distribution nglycans allowing precise comparison normal diseased brain hemispheresconclusionstogether data show first time complete profiling nglycomic changes wellcharacterised animal model neuroinflammation data represent pioneering step identify critical targets may modulate neuroinflammation neurodegenerative diseases,0.0
diabetic cataract nile grass rat longitudinal phenotypic study pathology formation abstractdiabetes major risk factor cataract leading cause blindness worldwide unmet need realistic model diabetic cataract mechanistic longitudinal studies existing models reflect key aspects complex human disease introduce characterize diabetic cataract nile grass rat ngr arvicanthis niloticus established model metabolic syndrome type 2 diabetes t2d conducted longitudinal study cataract 88 ngrs nondiabetic prediabetic diabetic stages metabolism oral glucose tolerance test ogtt results distinguished metabolic stages diverse cataract types observed course diabetes including cortical posterior subcapsular psc anterior subcapsular asc succeeded characteristic dotted ring stage animals onset ages diabetes cataract 443 vs 291 p001 665 vs 586 significant weeks females males respectively histological analysis revealed fiber disorganization vacuolar structures cellular proliferation migration cataractous lenses lens epithelial cells lecs nondiabetic young ngrs expressed stress marker grp78 lecs migrated cells lenses diabetic animals elucidating mechanisms underlying lec proliferation migration will clinically valuable prevention treatment posterior capsule opacification dreaded complication cataract surgery marked changes ncadherin expression emphasized role lec integrity cataractogenesis apoptotic cells dispersed equatorial areas early cataractogenesis study reveals diverse cataract types spontaneously develop diabetic ngr uniquely mirror cataract chronic course development individuals diabetes provide mechanistic insights early stages diabetic cataract unique characteristics make ngr highly suited mechanistic studies especially context metabolism diabetes aging,0.0
cornuside alleviates experimental autoimmune encephalomyelitis inhibiting th17 cell infiltration central nervous system j zhejiang univ sci b 2021 may 15 22 5 421430 doi 101631 jzusb2000771abstractthe present study conducted clarify therapeutic effect cornuside experimental autoimmune encephalomyelitis eae influence t helper 17 th17 cell regulatory t treg cell infiltration central nervous system rats randomly placed four treatment groups control eae eae+cornuside eae+prednisolone neurological function scores rats assessed daily second day eae rats began show neurological deficit symptoms four groups treated normal saline normal saline cornuside 150 mg kg prednisolone 5 mg kg respectively treatment discontinued two weeks spinal cord obtained hematoxylin eosin luxol fast blue staining well retinoic acid receptorrelated orphan receptor ror forkhead box protein p3 foxp3 immunohistochemical staining blood collected th17 treg cell flow cytometry testing serum levels interleukin il 17a il10 transforming growth factor tgf il6 il23 il2 measured via enzymelinked immunosorbent assay elisa compared rats eae group rats eae+cornuside eae+prednisolone groups began recover neurological deficits earlier greater degree improvement symptoms focal inflammation demyelination rorpositive cell infiltration reduced cornuside prednisolone treatment whereas foxp3positive cell numbers significantly different meanwhile number th17 cells il17a il6 il23 levels lower blood cornuside prednisolone treatment whereas number treg cells levels il10 tgf il2 markedly different cornuside can alleviate symptoms eae neurological deficits antiinflammatory immunosuppressive effects th17 cells may one therapeutic targetspmid33973423 doi101631 jzusb2000771,1.0
profiling serum neurofilament light chain glial fibrillary acidic protein primary progressive multiple sclerosis j neuroimmunol 2021 mar 5 354577541 doi 101016 jjneuroim2021577541 online ahead printabstractthis study examined utility serum neurofilament light chain snfl glial fibrillary acidic protein sgfap biomarkers primary progressive multiple sclerosis context clinical severity progression treatment using singlemolecule array quanterix serum protein concentrations measured twentyfive participants semiannually five years association levels either biomarker disease severity disease duration treatment group enrollment snfl level associated future clinical worsening precedent clinical worsening associated last sgfap measurement results suggest limited role biomarkers primary progressive disease managementpmid33725477 doi101016 jjneuroim2021577541,0.0
identification development therapeutic potential il10producing regulatory b cells multiple sclerosis j neuroimmunol 2021 feb 27 354577520 doi 101016 jjneuroim2021577520 online ahead printabstractregulatory b cells rare bcell subset widely known exert immunosuppressive function via production interleukin10 il10 mechanisms b10 cells special subset regulatory b cells immunoregulatory function fully attributed il10 unique roles animal model multiple sclerosis ms described well relevance ms patients review specifically focuses identification development b10 cells signals promote il10 production b cells roles b10 cells ms potential major challenges application b10based therapies mspmid33684831 doi101016 jjneuroim2021577520,0.0
neurology inflammatory bowel disease j neurol sci 2021 mar 27117426 doi 101016 jjns2021117426 online ahead printabstractinflammatory bowel diseases ibd chronic inflammatory conditions affecting digestive system comprising two main distinctive entities ulcerative colitis uc crohns disease cd besides gastrointestinal manifestations ibd causes extraintestinal manifestations central peripheral nervous system incidence neurological complications ibd ranges 025 475 pathophysiology neurological manifestations ibd mostly immune mediated dysfunction braingut axis arterial venous thromboembolism infections nutritional deficiencies sideeffects medications steroids metronidazole sulfasalazine antitnf antiintegrin antibodies contributory mechanisms patients ibd increased risk arterial venous stroke mainly periods exacerbations vasculitis extremely rare bidirectional association multiple sclerosis ibd relative risk comorbidity 154 153 risk multiple sclerosis ibd 155 risk ibd multiple sclerosis patients antitnf therapy contraindicated treatment patients ibd multiple sclerosis demyelinating disorders can also rare complication antitnf therapy optic neuritis transverse myelitis progressive myelopathy central nervous system infections epilepsy encephalopathy among uncommon neurological complications peripheral nervous system manifestations include peripheral neuropathy either demyelination axonal myasthenia gravis polymyositis dermatomyositis localized forms myositispmid33810878 doi101016 jjns2021117426,1.0
noninvasive brain stimulation assess neurophysiologic underpinnings lower limb motor impairment multiple sclerosis j neurosci methods 2021 mar 20109143 doi 101016 jjneumeth2021109143 online ahead printabstractbackground multiple sclerosis ms neuroinflammatory disease resulting axonal demyelination amalgamation symptoms commonly result decreased quality life due mobility dysfunction limited participation meaningful activitiesnew method use noninvasive brain stimulation nibs techniques specifically transcranial magnetic transcranial direct current stimulation essential understanding pathophysiological decrements related disease progression particularly regard motor impairments although research area primarily focused upper extremities new interest arisen understanding neurophysiological underpinnings lower limb impairment therefore purpose review first provide overview common nibs techniques used explore sensorimotor neurophysiology second summarize lower limb neuromuscular mobility impairments typically observed pwms third review current knowledge regarding interactions tmsassessed neurophysiology lower limb impairments pwms fourth provide recommendations future nibs studies based current gaps literatureresults pwms exhibit reduced excitability increased inhibitory neurophysiologic function related disease severity lower limb motor impairments comparison existing methods moreover promising results indicate use repetitive stimulation transcranial direct current stimulation may prime neural adaptability prove useful therapeutic tool ameliorating lower limb impairmentsconclusions studies informative promising additional studies necessary conclusive studies assessing objective measures lower limb impairments associated neurophysiological adaptations need evaluationpmid33757762 doi101016 jjneumeth2021109143,1.0
multicenter survey access care multiple sclerosisrelated trigeminal neuralgia j neurol sci 2021 mar 27 424117430 doi 101016 jjns2021117430 online ahead printabstractthe prevalence trigeminal neuralgia tn patients multiple sclerosis ms higher general population management can particularly challenging due number reasons including high recurrence rates lack msspecific treatment guidelines uncertainties pain pathophysiology aim crosssectional multicentre survey gather information current treatment modalities options msrelated tn across 23 italian ms centres initial medical management carbamazepine oxcarbazepine msrelated tn fairly homogeneous throughout italian centres commonly available surgical procedure microvascular decompression frequency types surgical procedures available locally differed considerably throughout ms centers unavailable one quarter survey reveals issues hamper optimal patient management underlines need consensus msrelated tn support healthcare professionals approach challenging condition facilitate development local guidelines aimed ensuring equity access care treatment optimizationpmid33838554 doi101016 jjns2021117430,0.0
disease reactivation patient secondary progressive multiple sclerosis switching treatment fingolimod siponimod eneurologicalsci 2021 may 15 23100346 doi 101016 jensci2021100346 ecollection 2021 junno abstractpmid34041374 pmcpmc8142249 doi101016 jensci2021100346,0.0
complete freund#39 s adjuvantfree experimental autoimmune encephalomyelitis dark agouti rats valuable tool multiple sclerosis studies j neuroimmunol 2021 mar 16 354577547 doi 101016 jjneuroim2021577547 online ahead printabstractexperimental autoimmune encephalomyelitis eae classically induced complete freunds adjuvant cfa immune response cfa confounding influence translational capacity eae multiple sclerosis model compare clinical cellular molecular properties syngeneic spinal cord homogenate sch sch + cfaimmunized dark agouti rats eae signs observed earlier cumulative clinical score higher without cfa also higher number immune cells infiltrates spinal cords noticed peak eae without cfa high spinal cord abundance cd8+cd11bc+mhc class ii+ cells detected schimmunized rats myelin basic protein specific response can elicited cells lymph nodes draining site sch immunization cfafree eae reliable multiple sclerosis modelpmid33765502 doi101016 jjneuroim2021577547,1.0
antioxidant mntbap effectively downregulate cd4 expression t cells vivo j neuroimmunol 2021 mar 8 354577544 doi 101016 jjneuroim2021577544 online ahead printabstractthe antioxidant mntbap previously shown downregulate surface expression cd4 molecule t cells observation obviously holds great potential impact number pathological human conditions including autoimmunity three different single doses mntbap reduced frequency cd4high cells however median florescent intensity mfi levels different initiation vivo pharmacotherapy vehicle control performed inc57bl 6 mice actively immunized experimental autoimmune encephalomyelitis eae contrast published reports mean frequency cd4high cells median fluorescent intensity mfi cd4 similar treatment groups 25day survival following active immunization among mntbap treated animals compared vehicle controls was166 69 days vs 236 27 days p value 005 conclude mntbap sack herzog 2009 sack herzog 2009 effectively downregulate cd4 expression t cells vivo probably due extensive mechanism distinguishes vitro model harding 1993 harding 1993 possesses toxic properties may limit clinic use possible doses deliver immunomodulation regulation cd4 expression saizawa et al 1987 saizawa et al 1987 limited availability specific tissues including cnspmid33756414 doi101016 jjneuroim2021577544,0.0
identification long noncoding rna traf3ip2as1 key regulator il17 signaling srsf10irf1act1 axis autoimmune diseases j immunol 2021 may 3ji2001223 doi 104049 jimmunol2001223 online ahead printabstractil17a plays essential role pathogenesis many autoimmune diseases including psoriasis multiple sclerosis act1 critical adaptor il17a signaling pathway study report antisense long noncoding rna traf3ip2as1 regulates act1 expression il17a signaling recruiting srsf10 downregulates expression irf1 transcriptional factor act1 interestingly found psoriasissusceptible variant traf3ip2as1 a4165g rs13210247 gainoffunction mutant furthermore identified mouse gene e130307a14rik homologous traf3ip2as1 similar ability regulate act1 expression il17a signaling importantly treatment lentiviruses expressing e130307a14rik srsf10 yielded therapeutic effects mouse models psoriasis experimental autoimmune encephalomyelitis findings suggest traf3ip2as1 srsf10 may represent attractive therapeutic targets treatment il17related autoimmune diseases psoriasis multiple sclerosispmid33941656 doi104049 jimmunol2001223,0.0
mri activity extended interval natalizumab dosing regimen multicentre italian study j neurol sci 2021 mar 6 424117385 doi 101016 jjns2021117385 online ahead printabstractbackground minimize risk progressive multifocal leukoencephalopathy rebound jcvpositive multiple sclerosis ms patients 24 natalizumab doses proposed extend administrations interval objective evaluate eid efficacy mri activity compared standard interval dosing sid methods observational multicentre retrospective cohort study starting 24th natalizumab infusion loss followup 2 years baseline three hundred sixteen patients enrolled median dose interval mdi following 24th infusion 5 weeks bimodal distribution modes 4 6 weeks patients grouped 2 categories according mean number weeks doses 5 weeks sid 5 weeks eidresults one hundred eightyseven patients sid group mdi 45 weeks 129 eid group mdi 61 weeks risk develop active lesions mri similar sid eid groups 6 12 months 24th natalizumab infusion respectively 427 95 ci084770 vs 471 95 ci016925 p 089 850 95 ci4051295 vs 655 95 ci2111100 p 056 eid regimen appear increase occurrence mri activity followupconclusion evidence reduced efficacy natalizumab eid setting regarding mri activity observation supports need bigger randomized study assess need change standard natalizumab dosing schedule better manage jcvpositive patientspmid33770708 doi101016 jjns2021117385,0.0
effect vitamin d supplements relapse rate expanded disability status scale edss multiple sclerosis ms systematic review metaanalysis int j prev med 2021 may 15 1242 doi 104103 ijpvmijpvm_208_20 ecollection 2021abstractbackground multiple sclerosis ms inflammatory disease controversies regarding role vitamin d supplements controlling relapse disability improvement treatmentobjective goal systematic review metaanalysis evaluate effect vitamin d supplements msrelated relapse expanded disability status scale edss methods searched databases include randomized clinical trials rcts published october 2018 included rcts singleblinded doubleblinded openlabel trials one main outcomes edss relapse vitamin d supplementation statistical analyses performed using revman 53 odds ratios 95 confidence intervals ci calculated relapse treatment arms mean difference calculated edss comparisonsresults nine articles included analysis nine studies five compared vitamin d supplement groups placebo group 1 studies four compared high lowdose vitamin d groups total 561 patients analyzed treated vitamin d instead placebo showed effect relapse rate 066 95 ci 028154 well edss mean difference 006 95ci 031 042 results studies comparing high vs lowdose vitamin d interventions showed significant effect relapse rate 108 95ci 029408 well final edss mean difference 017 95 ci 073 107 conclusions findings show vitamin d supplements high low dose significant effect relapse rate disability treatment ms patientspmid34211673 pmcpmc8223916 doi104103 ijpvmijpvm_208_20,0.0
relationship carotid atherosclerosis ultrasound parameters cardiac endothelial functions coronary heart disease patients purpose study aimed discover relationship carotid atherosclerosis ultrasound parameters cardiac endothelial functions coronary heart disease patientsmethods 150 patients coronary artery disease divided singlebranch group one coronary artery stenosis 50 doublebranch group two coronary arteries stenosis 50 multibranch group multiple coronary arteries stenosis 50 based severity patients coronary stenosis meanwhile 50 healthy volunteers admitted hospital routine health checks recruited control group study tested ultrasound parameters carotid artery atherosclerosis among subjects group common carotid artery sclerosis carotid artery compliance ac elastic coefficient ep pulse wave conduction velocity pwv including left ventricular end diastolic inner diameter lvedd left ventricular ejection fraction lvef endothelial function parameters endothelin1 et1 von willebrand factor vwf nitric oxide results study found ac ep pwv lvedd lvesd et1 vwf levels patients coronary artery disease higher corresponding levels control group p 005 values increased number coronary artery branches stenosis increased p 005 lvef patients coronary artery disease lower control group p 005 lvef decreased coronary artery branches stenosis increased p 005 correlation analysis indicated ultrasound parameter carotid atherosclerosis significant positive relation lvedd lvesd et1 vwf levels p 005 negative relation lvef levels p 005 conclusion ultrasound parameter carotid atherosclerosis cardiac function endothelial function can used early diagnosis coronary heart diseasekeywords coronary heart disease cardiac function carotid atherosclerosis early diagnosis endothelial function ultrasound,0.0
lipid receptor g2amediated signal pathway plays critical role inflammatory response promoting classical macrophage activation j immunol 2021 may 3ji2000231 doi 104049 jimmunol2000231 online ahead printabstractmacrophage polarization dynamic integral process tissue inflammation remodeling study describe lipoproteinassociated phospholipase a2 lppla2 plays important role controlling inflammatory macrophage m1 polarization rodent experimental autoimmune encephalomyelitis eae monocytes multiple sclerosis ms patients specific inhibition lppla2 led ameliorated eae via markedly decreased inflammatory demyelinating property m1 effects lppla2 m1 function mediated lysophosphatidylcholine bioactive product oxidized lipids hydrolyzed lppla2 jak2independent activation stat5 upregulation irf5 process directed g2a receptor found differentiated m1 monocytes ms patients m1 polarization inhibited g2a neutralizing ab led inhibited disease rat eae addition g2adeficient rats showed ameliorated eae inhibited autoimmune response study revealed mechanism lipid metabolites control macrophage activation function modification lead new therapeutic approach ms inflammatory disorderspmid33941654 doi104049 jimmunol2000231,1.0
gpcromics homeostatic diseaseassociated human microglia front immunol 2021 may 14 12674189 doi 103389 fimmu2021674189 ecollection 2021abstractgproteincoupled receptors gpcrs critical sensors affecting state eukaryotic cells get systematic insight gpcrome microglia analyzed publicly available rnasequencing data bulk single cells obtained human mouse brains identified 17 rhodopsin adhesion family gpcrs robustly expressed microglia human brains including homeostasisassociated genes cx3cr1 gpr34 gpr183 p2ry12 p2ry13 adgrg1 expression microglial core genes lost upon culture isolated cells ex vivo acquired human induced pluripotent stem cell ipsc derived microglial precursors transplanted mouse brains cxcr4 ptger4 higher expressed subcortical white matter compared cortical grey matter microglia adgrg1 downregulated microglia obtained normalappearing white grey matter tissue multiple sclerosis ms brains singlecell rna sequencing microglia active lesions obtained early ms revealed downregulation homeostasisassociated gpcr genes upregulation cxcr4 expression small subset msassociated lesional microglia functional presence low levels cxcr4 human microglia confirmed using flow cytometry transwell migration towards sdf1 microglia abundantly expressed gpcr downstream signaling mediator genes gnai2 i2 gnas s gna13 13 latter particularly white matter drugs several microglia gpcrs available target microglia brain diseases conclusion transcriptome profiling allowed us identify expression gpcrs may contribute brain patho physiology diagnostic therapeutic potential human microgliapmid34054860 pmcpmc8160299 doi103389 fimmu2021674189,0.0
translational block stroke constructive quot outoftheboxquot reappraisal front neurosci 2021 may 14 15652403 doi 103389 fnins2021652403 ecollection 2021abstractwhy can still translate preclinical research clinical treatments acute strokes despite 1000 successful preclinical studies drugs concepts acute stroke two reached clinical translation translational block yet continue routinely model strokes using almost concepts used 30 years methodological improvements criteria last decade shed light solved problem conceptual analysis review current status reappraise thinking outofthebox edges query scientific fields also faced translational failures find common denominators parallel query migraine multiple sclerosis hypothermia hypoxic encephalopathy achieved significant translation successes view ischemic stroke chronic relapsing vascular disease secondary prevention strategies also successful translation finally based lessons learned propose stroke modeled preclinical clinical scientists editors grant reviewers industry reconsider routine way conducting research translational success stroke treatments may eventually require bold change solutions outside boxpmid34054413 pmcpmc8160233 doi103389 fnins2021652403,0.0
fasudil enhances phagocytosis myelin debris expression neurotrophic factors cuprizoneinduced demyelinating mice neurosci lett 2021 apr 7135880 doi 101016 jneulet2021135880 online ahead printabstractmultiple sclerosis ms mainly associated neuroinflammation demyelination central nervous system cns failure remyelination results persistent neurological dysfunction fasudil typical rho kinase inhibitor exhibited beneficial effects several models neurodegenerative disorders study showed fasudil promoted uptake myelin debris microglia via cell experiments cuprizone cpz induced demyelinating model vitro microglia phagocytic debris exhibited enhanced expression brainderived neurotrophic factor bdnf glial cellderived neurotrophic factor gdnf conditioned medium promoted maturation oligodendrocyte precursor cells opcs meanwhile fasudil upregulated trem2 dap12 pathway positively regulated phagocytosis myelin debris microglia similarly vivo fasudil intervention enhanced clearance myelin debris upregulated expression bdnf gdnf microglia promoted formation oligo2+ pdgfr+ opcs maturation mbp + oligodendrocytes brain results showed fasudil targeted phagocytic function microglia effectively clearing myelin debris produced pathological process possibly upregulating trem2 dap12 pathway accompanied increased expression bdnf gdnf however precise mechanism underlying effects fasudil promoting phagocytic effects neurotrophic factors remains elucidatedpmid33838256 doi101016 jneulet2021135880,1.0
serial lipocalin 2 oncostatin m levels reflect inflammation status treatment response axial spondyloarthritis background informative serum biomarkers monitoring inflammatory activity treatment responses axial spondyloarthritis axspa lacking assessed whether lipocalin 2 lcn2 oncostatin m osm roles inflammation bone remodeling may accurately reflect chronic joint inflammation treatment response axspa previous reports animal models showed involvement lcn2 osm joint gut inflammation asked whether also play role human axspamethodswe analyzed longitudinal observational axspa cohort 286 patients yearly clinical assessments concurrent measurements serum lcn2 osm 1204 serum samples mean 4 years biomarker levels correlated mri scoring treatment responseresultspersistent transient elevation lcn2 osm observed axspa patients persistent elevation lcn2 osm crp correlated sacroiliac joint sij mri sparcc scores pearsons correlation p 00005 0005 lcn2 osm respectively suggesting lcn2 osm outperforms crp reflective sij inflammation observed concordant discordant patterns lcn2 osm relationship back pain cardinal clinical symptom axspa twentysix percent 73 286 patients remained clinically serologically active casa sixty percent 173 286 patients became clinically quiescent back pain resolved 53 92 173 serologically active cqsa indicating pain control may indicate control joint inflammation reflected positive mri imaging sij respect treatment responses transient elevation lcn2 osm time predictive better response treatmentsconclusionin axspa persistent lcn2 osm elevation reflects chronic sij inflammation suboptimal treatment response cohort half currently deemed clinically quiescent patients back pain resolved continued demonstrate chronic joint inflammation lcn2 osm profiling outperforms crp predictive measure provides objective assessment chronic local inflammation axspa patients,0.0
metabolic aspects adenosine functions brain front pharmacol 2021 may 14 12672182 doi 103389 fphar2021672182 ecollection 2021abstractadenosine acting gprotein coupled adenosine receptors intracellularly plays complex role multiple physiological pathophysiological processes modulating neuronal plasticity astrocytic activity learning memory motor function feeding control sleep aging adenosine involved stroke epilepsy neurodegenerative pathologies extracellular concentration adenosine brain tightly regulated adenosine may generated intracellularly central nervous system degradation amp hydrolysis sadenosyl homocysteine exit via bidirectional nucleoside transporters extracellularly metabolism released nucleotides inactivation extracellular adenosine occurs transport neurons neighboring cells followed either phosphorylation amp adenosine kinase deamination inosine adenosine deaminase modulation nucleoside transporters enzymatic activities involved metabolism adenosine affecting levels nucleoside activity adenosine receptors role onset development central nervous system disorders can also target drugs treatment review focus contribution 5nucleotidases adenosine kinase adenosine deaminase amp deaminase ampactivated protein kinase nucleoside transporters epilepsy cognition neurodegenerative diseases particular attention amyotrophic lateral sclerosis huntingtons disease include several examples involvement components adenosine metabolism learning possible use modulators enzymes involved adenosine metabolism nucleoside transporters amelioration cognition deficitspmid34054547 pmcpmc8160517 doi103389 fphar2021672182,0.0
uptake influenza vaccination among persons inflammatory bowel disease multiple sclerosis rheumatoid arthritis populationbased matched cohort study cmaj open 2021 may 14 9 2 e510e521 doi 109778 cmajo20200105 print 2021 aprjunabstractbackground individuals immunemediated inflammatory diseases inflammatory bowel disease multiple sclerosis rheumatoid arthritis increased risk influenza related complications examined compared uptake influenza vaccination among people without diseases well influence psychiatric comorbidity vaccine uptakemethods using administrative data apr 1 1984 mar 31 2016 conducted retrospective matched cohort study manitoba canada matched persons 18 years age older diagnosis inflammatory bowel disease multiple sclerosis rheumatoid arthritis immunemediated inflammatory disease cohorts persons diagnoses control cohorts age sex region identified cohort members mood anxiety disorder depression anxiety disorders bipolar disorder identified influenza vaccinations billing codes using binomial regression modelled difference proportion immunemediated inflammatory disease matched cohorts vaccinated annually adjustment sociodemographic characteristics comorbidity immune therapy tested additive interaction effects persons cohort presence mood anxiety disorderresults identified 32 880 individuals 1 immunemediated inflammatory diseases 10 148 inflammatory bowel disease 6158 multiple sclerosis 16 975 rheumatoid arthritis total 164 152 controls fiscal year 2015 8668 413 95 confidence interval ci 406 420 20 982 persons immunemediated inflammatory disease received influenza vaccination rate higher among controls 35 238 104 634 337 95 ci 334 340 adjustment participants immunemediated inflammatory disease mood anxiety disorder 644 95 ci 579 710 greater uptake vaccination participants without disease among participants without immunemediated inflammatory disease mood anxiety disorder associated 454 95 ci 420 489 greater uptake vaccination however observed subadditive interaction immunemediated inflammatory disease psychiatric status 138 95 ci 226 050 interpretation uptake influenza vaccination consistently low populations immunemediated inflammatory disease although psychiatric morbidity associated greater vaccine uptake manitobans negatively interacts diseases reduce uptake changes care delivery needed mitigate gap carepmid33990365 doi109778 cmajo20200105,0.0
pathological drivers neurodegeneration suspected nonalzheimers disease pathophysiology background little known heterogeneous etiology suspected nonalzheimers pathophysiology snap group subjects neurodegeneration absence amyloid using antemortem mri pathological data investigated etiology snap association neurodegenerative pathologies structural medial temporal lobe mtl measures amyloidnegative subjectsmethodssubjects antemortem mri autopsy data selected adni n63 university pennsylvania n156 pathological diagnoses semiquantitative scores mtl tau neuritic plaques synuclein tdp43 pathology mtl structural mri measures antemortem t1weighted mri scans obtained amyloid status a+ determined cerad score neurodegeneration status n+ n hippocampal volumeresultssnap reflects heterogeneous group pathological diagnoses adni snap an+ significantly neuropathological diagnoses a+n+ group tau pathology associated hippocampal entorhinal cortex brodmann area 35 volume thickness tdp43 pathology hippocampal volumeconclusionsnap heterogeneous profile mixed pathologies a+n+ moreover role tdp43 tau pathology driving mtl neurodegeneration absence amyloid supported,0.0
role lysosomes physiological activities diseases therapy abstractlong known digestive organelles lysosomes now emerged multifaceted centers responsible degradation nutrient sensing immunity growing evidence also implicates role lysosomerelated mechanisms pathologic process review discuss physiological function lysosomes importantly homeostasis lysosomes disrupted several diseases including atherosclerosis neurodegenerative diseases autoimmune disorders pancreatitis lysosomal storage disorders malignant tumors atherosclerosis gaucher disease dysfunction lysosomes changes cytokine secretion macrophages partially inflammasome activation neurodegenerative diseases defect autophagy facilitates accumulation toxic protein dysfunctional organelles leading neuron death lysosomal dysfunction demonstrated pathology pancreatitis abnormal autophagy activation inhibition revealed autoimmune disorders tumor microenvironment malignant phenotypes including tumorigenesis growth regulation invasion drug resistance radiotherapy resistance tumor cells behaviors tumorassociated macrophages fibroblasts dendritic cells t cells also mediated lysosomes based findings series therapeutic methods targeting lysosomal proteins processes developed bench bedside word present researches corroborate lysosomes pivotal organelles understanding pathology atherosclerosis neurodegenerative diseases autoimmune disorders pancreatitis lysosomal storage disorders malignant tumors developing novel therapeutic strategies,0.0
upregulated antiangiogenic mir4245p type 1 diabetes model subclinical cardiovascular disease correlates endothelial progenitor cells cxcr1 2 parameters vascular health background spite clinical progress cardiovascular disease cvd remains predominant cause mortality worldwide overexpression studies animals proven mir4245p antiangiogenic properties type 1 diabetes mellitus t1dm without cvd displays endothelial dysfunction reduced circulating endothelial progenitor cells cepcs offers model subclinical cvd therefore explored mir4245p cytokines vascular health t1dmmethodstwentynine wellcontrolled t1dm patients cvd 20matched controls studied cytokines il8 tnf il7 vegfc cepcs cd45dimcd34+cd133+ cells exvivo proangiogenic cells pacs fibronectin adhesion assay faa measured mir4245p plasma peripheral blood mononuclear cells pbmc along mrnas pbmc evaluatedresultswe found elevation il7 p 0008 il8 p 0003 tnf p 0041 vegfc p 0013 upregulation mrna cxcr1 p 0009 cxcr2 p 0001 reduction cepcs p 0001 pacs p 0001 faa p 0017 t1dm mir4245p upregulated t1dm pbmc p 0001 mir4245p negatively correlated cepcs p 0006 pacs p 0005 faa p 0001 positively hba1c p 0001 il7 p 0008 il8 p 0017 vegfc p 0007 cxcr1 p 002 cxcr2 p 0001 roc curve analyses showed 1 mir4245p biomarker t1dm p 0001 2 significant upregulation mir4245p defining subclinical cvd occurred hba1c 465 mmol mol p 0002 conclusionwe validated animal research antiangiogenic properties mir4245p t1dm mir4245p may biomarker onset subclinical cvd hba1c 465 mmol mol prediabetes thus mir4245p potential use cvd monitoring whilst antimir4245pbased therapies may used reduce cvd morbidity mortality t1dm,0.0
relationship anxiety depression respiratory functions patients relapsingremitting multiple sclerosis abstractbackgroundpsychiatric symptoms common multiple sclerosis relationship emotional state respiratory function unclear patients aimed evaluate relationship clinical characteristics anxiety depression status respiratory functions patients relapsingremitting multiple sclerosis rrms methodthe research planned prospective casecontrol study ninety rrms patients 50 healthy controls included study ms diagnosis confirmed according revised 2017 mcdonaldnulls criteria disability divided two subgroups according expanded disability status scale edss 35 3555 beck anxiety beck depression inventories evaluated pulmonary function test performed computerized spirometry device forced expiratory volume1st second fev1 forced vital capacity fvc fev fvc peak expiratory flow pef maximal expiratory flow mef peak inspiratory flow pif maximal inspiratory flow mif values obtainedresultsthere 90 rrms patients mean age 38681095 years 58 6440 female study anxiety depression scores patients significantly higher control group p002 0002 fvc fev1 values lower patients higher beck depression scores p0012 0007 fvc fev1 mef50 pif values lower patients higher beck anxiety scores p0002 0002 0030 0027 edss number attacks fixed low moderate correlation anxiety fev1fvc p0001 r367 0360 respectively low negative correlation depression fev1 p0045 r0214 conclusionanxiety depression scores higher patients rrms depression anxiety particularly associated low fvc fev1 patients,0.0
activityregulated cytoskeletonassociated protein activityregulated gene 31 arc arg31 enhances dendritic cell vaccination experimental melanoma oncoimmunology 2021 may 14 10 1 1920739 doi 101080 2162402x20211920739abstractdendritic cell dc vaccination proven effective safe adjuvant cancer immunotherapies presence dcs within tumor microenvironment promotes adaptive antitumor immunity enhancement dc migration toward tumor microenvironment following dc vaccination might represent one possible approach increase therapeutic efficacy recent findings suggest activityregulated cytoskeletonassociated protein activityregulated gene 31 arc arg31 critical regulator dc migration context autoimmune diseases aimed investigate impact arc arg31 expression dcbased cancer vaccines end dc migration capacity well induction t cellmediated antitumor immunity assessed experimental b16 melanoma model arc arg31 arc arg31expressing bmdcs applied subcutaneous vaccine antigen presentation dcs critical unleashing effective t cell mediated antitumor immune responses arc arg31 expression enhanced dc migration toward tumor secondary lymphoid organs moreover arc arg31expressing bmdcs shape tumor immune microenvironment facilitating tumor recruitment antigenspecific effector t cells thus arc arg31 may represent novel therapeutic target dcs order increase therapeutic efficacy dc vaccinationpmid34026332 pmcpmc8128181 doi101080 2162402x20211920739,0.0
influence comorbidities healthcare expenditures perceived physical mental health status among adults multiple sclerosis propensity scorematched us nationallevel study clinicoecon outcomes res 2021 may 13 13377394 doi 102147 ceors305154 ecollection 2021abstractobjective evaluate effect comorbidities healthcare expenditures perceived physical mental health status among adults multiple sclerosis ms compared propensity scorematched nonms controlsmethods retrospective crosssectional matched cohort study conducted using medical expenditure panel survey 20052015 data base study sample consisted adults age 18 years alive positive total healthcare expenditures survey calendar year adults ms propensitymatched 11 nonms controls based age gender race ethnicity using greedy matching algorithm healthcare expenditures consisted total subtypes expenditures health status consisted perceived physical mental health status comorbidities identified using icd9cm clinical classification system codes ordinary least squares regression multinomial logistic regression used analyze healthcare expenditures health status variables respectivelyresults final study sample consisted 541 adults ms nonms control groups propensity score matching adjusting potential confounders individuals ms greater total subtypes expenditures compared nonms controls several comorbidities eg depression hypertension significantly associated increased healthcare expenditures yearly average total expenditures expressed 2018 us significantly p0001 higher adults ms 29 396 propensity scorematched nonms adults 7875 moreover adjusting individuallevel factors adults ms experienced 363 p0001 higher total expenditures compared propensity scorematched nonms controls individuals ms likely report poorer physical good mental health status compared propensity scorematched nonms controls several comorbidities eg anxiety depression significant independent predictors poorer health status example adults ms four times likely 410 95 ci 242696 report fair poor physical health status compared excellent good physical health status compared nonms controls adults ms 42 142 95 ci 101199 likely propensity scorematched nonms controls report good rather good excellent mental health status however difference adults ms propensity scorematched nonms controls terms reporting fair poor good excellent mental health statusconclusion findings study indicate substantial economic health status burdens among adults ms us nationallevel significantly influenced comorbiditiespmid34017188 pmcpmc8129918 doi102147 ceors305154,0.0
association menopausal hormone therapy risk neurodegenerative diseases implications precision hormone therapy alzheimers dement n y 2021 may 13 7 1 e12174 doi 101002 trc212174 ecollection 2021abstractintroduction impact menopausal hormone therapy ht ageassociated alzheimers neurodegenerative diseases ndds remains unresolved determine effect ht formulation type duration risk ndds retrospective analysis performed using 10year humana claims datasetmethods study population included women aged 45 years older without claim records ht medications patients diagnosed ndds including alzheimers disease ad parkinsons disease pd dementia multiple sclerosis ms amyotrophic lateral sclerosis als identified relative risk rr ratios 95 confidence intervals ci combined ndds ad pd dementia ms als determined cumulative hazard ratios determined investigate association ht ndds different age groupsresults 379 352 women without claim records ht use ht associated significantly reduced risk combined ndds rr 042 95 ci 040043 p 0001 average followup time 51 23 years formulations containing natural steroids 17estradiol progesterone associated greater reduction ndd risk oral ht users showed significantly reduced rrs 042 041044 p 0001 combined ndds compared nonht users rrs transdermalht users significantly decreased allcause dementia 073 060088 p 0001 ms 055 036084 p 0005 greatest reduction risk ndd ad dementia emerged patients aged 65 years older protective effect longterm therapy 1 year combined ndds ad pd dementia greater compared shortterm therapy 1 year discussion ht associated reduced risk ndds including ad dementia greater duration therapy natural steroid formulations associated greater efficacy findings advance precision ht prevent ndds including adpmid34027024 pmcpmc8118114 doi101002 trc212174,0.0
efficacy cannabinoids spasticity chronic pain patient cooccurrence multiple sclerosis neurofibromatosis type 1 eur j case rep intern med 2021 may 13 8 5 002424 doi 1012890 2021_002424 ecollection 2021abstractneurofibromatosis type 1 nf1 rare autosomal dominant disease involving skin central nervous system cns also characterized skeletal spinal schwannomas may cause chronic neurogenic pain furthermore pain nf1 underestimated even though impact quality life multiple sclerosis ms common acquired demyelinating disease may later stages present refractory spasticity particularly lower limbs oromucosal cannabinoid sprays currently available spasticity treatment ms encouraging results ms pain data reported regarding use cannabinoids nf1 report successful treatment chronic neurogenic pain spasticity patient cooccurrence nf1 ms poor response standard approacheslearning points chronic pain possible complication several neurological conditions may show poor response standard drugs thus affecting quality lifeoromucosal cannabinoid sprays routinely used multiple sclerosis spasticitycannabinoids may also effective neurogenic pain neurofibromatosis type 1pmid34123937 pmcpmc8191353 doi1012890 2021_002424,1.0
bmscs differentiated neurons astrocytes oligodendrocytes alleviated inflammation demyelination eae mice models plos one 2021 may 13 16 5 e0243014 doi 101371 journalpone0243014 ecollection 2021abstractmultiple sclerosis ms complex progressive neuroinflammatory disease associated autoimmunity currently effective therapeutic strategy poorly found ms experimental autoimmune encephalomyelitis eae widely used study pathogenesis ms cumulative research shown bone marrow mesenchymal stem cells bmscs transplantation treat eae animal models mechanism divergent systematically evaluated whether bmscs can differentiate neurons astrocytes oligodendrocytes alleviate symptoms eae mice used immunofluorescence staining detect map2 gfap mbp evaluate whether bmscs can differentiate neurons astrocytes oligodendrocytes effect bmscs transplantation inflammatory infiltration demyelination eae mice detected hematoxylineosin luxol fast blue lfb staining respectively inflammatory factors expression detected elisa rtqpcr respectively results showed bmscs induced differentiate neuron cells astrocytes oligodendrocyte vivo vitro bmscs transplanted eae mice easier differentiate normal mice moreover transplanted bmscs reduced neurological function scores disease incidence eae mice bmscs transplantation alleviated inflammation demyelination eae mice finally found bmscs transplantation downregulated levels proinflammatory factors tnf il1 ifn upregulated levels antiinflammatory factors il10 tgf conclusion study found bmscs alleviate inflammatory response demyelination eae mice may achieved differentiation bmscs neurons astrocytes oligodendrocytes eae micepmid33983943 doi101371 journalpone0243014,1.0
urinederived induced pluripotent neural stem cells modeling neurological diseases abstractneurological diseases mainly modeled using rodents gene editing surgery injury approaches however differences humans rodents terms genetics neural development physiology pose limitations studying disease pathogenesis rodent models neuroscience research past decade generation induced pluripotent stem cells ipscs induced neural stem cells inscs reprogramming somatic cells offers powerful alternative modeling neurological diseases testing regenerative medicines among different somatic cell types urinederived stem cells uscs ideal cell source ipsc insc reprogramming uscs highly proliferative multipotent epithelial nature easier reprogram skin fibroblasts addition use uscs represents simple lowcost noninvasive procedure generating ipscs inscs review describes cellular molecular properties uscs differentiation potency different reprogramming methods generation ipscs inscs potential applications modeling neurological diseases,0.0
time quotas achieve racial ethnic representation multiple sclerosis trials front neurol 2021 may 13 12680912 doi 103389 fneur2021680912 ecollection 2021no abstractpmid34054715 pmcpmc8155278 doi103389 fneur2021680912,0.0
lumbar ventricular csf concentrations extracellular matrix proteins shunt surgery idiopathic normal pressure hydrocephalus background idiopathic normal pressure hydrocephalus inph reversible cns disease characterized disturbed cerebrospinal fluid csf dynamics changes extracellular matrix ecm composition might involved pathophysiology inph aim study explore possible differences lumbar ventricular csf concentrations ecm markers brevican neurocan matrix metalloproteinases mmps tissue inhibitor metalloproteinase1 timp1 relation clinical symptoms inph patients shunt surgerymethodspaired lumbar ventricular csf collected 31 inph patients four months shunt surgery csf analysed concentrations tryptic peptides originating brevican neurocan using mass spectrometrybased panel mmp1 2 9 10 timp1 using fluorescent electrochemiluminescent immunoassaysresultsbrevican neurocan peptide levels influenced csf origin mmp1 2 10 timp1 increased p 00005 mmp9 decreased p 00003 lumbar csf compared ventricular csf general trend ecm proteins increase following shunt surgery ventricular timp1 inversely correlated overall symptoms rho 062 p 00001 csf concentrations majority brevican neurocan peptides increased inph patients history cardiovascular disease p 0001 auc 084094 compared withoutconclusionlevels cnsspecific proteins brevican neurocan differ lumbar ventricular csf whereas increase several cnsunspecific mmps timp1 lumbar csf suggests contribution peripheral tissues increase ecm proteins csf following shunt surgery indicate disturbed ecm dynamics inph restored restitution csf dynamics,0.0
identification firstinclass inhibitors kallikreinrelated peptidase 6 promote oligodendrocyte differentiation j med chem 2021 may 5 doi 101021 acsjmedchem0c02175 online ahead printabstractmultiple sclerosis ms autoimmune demyelinating disease central nervous system cns causes severe motor sensory cognitive impairments kallikreinrelated peptidase klk 6 abundant serine protease secreted cns mainly oligodendrocytes myelinproducing cells cns klk6 assumed robust biomarker ms since highly increased cerebrospinal fluid csf ms patients report design biological evaluation klk6s lowmolecularweight inhibitors paraaminobenzyl derivatives interestingly selected hit compounds selective klk6 proteolytic network encompassing klk1 plasmin also participate development ms physiopathology moreover hits found noncytotoxic primary cultures murine neurons oligodendrocyte precursor cells opcs among two compounds 32 42 shown promote differentiation opcs mature oligodendrocytes vitro constituting thus emerging leads development regenerative therapiespmid33949859 doi101021 acsjmedchem0c02175,1.0
siglec1 cd169 marker active neuroinflammation brain blood multiple sclerosis patients sci rep 2021 may 13 11 1 10299 doi 101038 s41598021897860abstractwe aimed evaluate siglec1 cd169 biomarker multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd evaluate presence siglec1+ myeloid cells demyelinating diseases performed flow cytometrybased measurements siglec1 expression monocytes 86 ms patients 41 nmosd patients 31 healthy controls additionally histologically evaluated presence siglec1+ myeloid cells acute chronic ms brain lesions well neurological diseases found elevated siglec1 expression 16 86 186 ms patients 4 41 98 nmosd patients almost ms patients high siglec1 levels received exogenous interferon beta immunomodulatory treatment small fraction ms patients without interferon treatment increased siglec1 expression cohort siglec1 expression monocytes wasapart patients receiving interferon treatmentnot significantly increased patients ms nmosd levels associated severe disease siglec1+ myeloid cells abundantly present active ms lesions well range acute infectious malignant diseases central nervous system chronic ms lesions presence siglec1+ myeloid cells brain lesions used investigate activity inflammatory cns lesionpmid33986412 doi101038 s41598021897860,1.0
calcium channelopathies intellectual disability systematic review background calcium ions involved several human cellular processes including corticogenesis transcription synaptogenesis nevertheless relationship calcium channelopathies ccs intellectual disability id global developmental delay gdd poorly investigated hypothesised ccs play major role development id gdd gain lossoffunction variants calcium channel genes can induce id gdd result performed systematic review investigate contribution ccs potential mechanisms underlying involvement id gdd advancements cell animal models treatments brain anomalies patients ccs existing gaps knowledge performed systematic search pubmed embase clinvar omim clingen gene reviews decipher lovd databases search articles records published march 2021 following search strategies employed id calcium channel mental retardation calcium channel gdd calcium channel developmental delay calcium channelmain bodya total 59 reports describing 159 cases found pubmed embase clinvar lovd databases variations ten calcium channel genes including cacna1a cacna1c cacna1i cacna1h cacna1d cacna2d1 cacna2d2 cacna1e cacna1f cacna1g found associated id gdd variants exhibited gainoffunction effect severe profound id gdd observed cases gainoffunction variants compared lossoffunction cacna1e cacna1g cacna1f cacna2d2 cacna1a associated severe phenotype furthermore 157 copy number variations cnvs spanning calcium genes identified decipher database leading genes included cacna1c cacna1a cacna1e overall underlying mechanisms included gain lossoffunction alteration kinetics activation inactivation dominantnegative effects truncated forms alpha1 subunits forty identified cases featured cerebellar atrophy identified cell animal studies focused mechanisms id gdd relation ccs scarcity studies treatment options id gdd vivo vitroconclusionour results suggest ccs play major role id gdd gain lossoffunction variants associated id gdd mechanisms underlying involvement need scrutiny,0.0
sildenafil alleviates murine experimental autoimmune encephalomyelitis triggering autophagy spinal cord front immunol 2021 may 13 12671511 doi 103389 fimmu2021671511 ecollection 2021abstractmultiple sclerosis ms neuroinflammatory chronic central nervous system cns disease affects millions people worldwide search promising drugs treatment ms led studies sildenafil phosphodiesterase type 5 inhibitor pde5i shown possess neuroprotective effects experimental autoimmune encephalomyelitis eae animal model ms previously shown sildenafil improves clinical score eae mice via modulation apoptotic pathways signaling pathways previously covered therefore aim present study investigate effects sildenafil treatment autophagy nitrosative stress signaling pathways eae 24 female c57bl 6 mice divided following groups control received water b eae eae untreated mice c sild eae mice treated 25mg kg sildenafil sc results showed eae mice presented pronitrosative profile characterized high tissue nitrite levels lowered levels penos high levels inos furthermore decreased levels lc3 beclin1 atg5 suggests impaired autophagy decreased levels ampk spinal cord also detected eae mice surprisingly treatment sildenafil inhibited nitrosative stress augmented levels lc3 beclin1 atg5 pcreb bdnf decreased mtor levels well augmented pampk conclusion propose sildenafil alleviates eae activating autophagy via enosnoampkmtorlc3beclin1atg5 enosnoampkmtorcrebbdnf pathways spinal cordpmid34054847 pmcpmc8156813 doi103389 fimmu2021671511,1.0
correction design evaluation usercentered exergames patients multiple sclerosis multilevel usability feasibility studies jmir serious games 2021 may 13 9 2 e30326 doi 102196 30326abstract corrects article doi 102196 22826 pmid33983893 doi102196 30326,0.0
study probable genotoxic effects zolone phosalone exposure mice bone marrow derived cells background aimapproximately 2 million tonnes pesticides utilized annually worldwide phosalone pln organophosphorus pesticide acts insecticide acaricide control pests crops nuts citrus fruits pomegranates stone fruits grapes potatoes artichokes purpose study evaluate possible genotoxic effects following exposure pln cells derived mouse red bone marrowmaterials methodssixty mice divided 6 groups including cyclophosphamide 40 mg kg ip pln 6 12 20 40 mg kg exposure gavage 1 5 days exposure animals euthanized genotoxicity assays done bone marrow extracted cellsresultscomet assay shows time dosedependent toxicity dna degradation observed 5day exposure p 005 also pln significantly increased mnpce pce ratio 12 20 mg kg administration significant difference reported doses 6 40 mg kg bw negative control groupconclusionour results suggested serious concern potential effects biological life related disease inductions however studies need confirm exact mechanism pln genotoxicity cause diverse response activity 40 mg kg study also showed increasing dose pln reduces mnnce total cells ratio may indicate possibility bone marrow suppression results emphasize need seriously limit use compound agricultural pesticide,0.0
optic chiasm involvement aqp4 antibodypositive nmo mog antibodyassociated disorder backgroundoptic neuritis often presenting symptom inflammatory central nervous system demyelinating disordersobjectiveto compare frequency pattern optic chiasm involvement patients aquaporin4immunoglobulin g aqp4igg associated patients myelin oligodendrocyte glycoproteinimmunoglobulin g mogigg associated onmethodsretrospective review patients evaluated mayo clinic stanford university ramathibodi hospital found 1 2 either mogigg aqp4igg cellbased assay 3 magnetic resonance imaging mri time mri reviewed contrast enhancement optic chiasm pattern involvementresultsone hundred fiftyfour patients 74 aqp4igg 80 mogigg included among patients aqp4iggon 20 chiasmal involvement compared 16 patients mogiggon p 066 patients chiasmal involvement longitudinally extensive optic nerve enhancement orbit extending chiasm identified 54 mogiggon patients compared 7 aqp4iggon patients p 001 conclusionchiasmal involvement mogiggon aqp4iggon occur similar frequencies previously reported furthermore mogiggon chiasmal involvement likely part longitudinally extensive optic nerve lesion,1.0
assessing causality means naranjo scale paediatric patient life threatening respiratory failure alemtuzumab administration case report background alemtuzumab t cell depleting antibody agent used induction immunosuppressant therapy solid organ transplant recipients addition increasingly used treat severe glucocorticoidresistant graft rejection despite effectiveness treatment severe adverse events reported related alemtuzumab administration present similar event illustrating severity adverse drug reaction adr highlight structure causality assessment provides approaching casecase presentationwe report case lifethreatening respiratory failure alemtuzumab administration 17 year old paediatric kidney transplant recipient developed near fatal severe respiratory circulatory failure based acute respiratory distress syndrome ards diffuse alveolar oedema haemoptysis hours second alemtuzumab administration questionable whether alemtuzumab regarded origin reaction order assess causality reaction well structure clinical reasoning applied widely used adr probability scale systematically review casediscussion conclusionsour case shows severe adr alemtuzumab administration illustrates importance proper causality assessment structure provides benefit clinical pharmacology consultation severe reaction suspected adr taking case example demonstrate added value structured causality assessment clinical reasoning generating differential diagnoses,0.0
investigating healthrelated quality life rare diseases case study utility value determination patients cln2 disease neuronal ceroid lipofuscinosis type 2 background utility studies enable preferencebased quantification diseases impact patients healthrelated quality life hrqol often difficult obtain utility values rare neurodegenerative conditions due cognitive burden direct elicitation methods limited size patient caregiver populations cln2 disease neuronal ceroid lipofuscinosis type 2 ultrarare progressive condition published utility data fully capturing disease stages case study demonstrates utility values can estimated ultrarare paediatric diseases asking clinicians complete eq5d5l questionnaires based vignettes describing stages cln2 diseasemethodsan indirect elicitation method using proxyreporting clinical experts adopted eighteen vignettes developed describing nine progressive disease stages defined motor language domain scores cln2 clinical rating scale individuals treated cerliponase alfa standard care eight clinical experts experience treating cln2 disease cerliponase alfa current standard care completed proxy version 2 eq5d5l online reading vignettes resulting scores converted eq5d5l utility values disease stage using uk german spanish value setsresultsutility values typically anchored 0 equivalent death 1 full health decreased cln2 disease progression results spanned maximum range utility scale assigned utility values consistently higher patients receiving cerliponase alfa standard care differences statistically significant 6 severe disease stages p 005 analysis individual dimensions eq5d5l showed greatest differences patients treated cerliponase alfa standard care occurred pain dimension differences mean scores ranged difference 18 notable differences also observed anxiety depression dimension differences mean scores ranged 01 10 conclusionsthis study demonstrates feasible methodology eliciting utility values cln2 disease indicating hrqol declines disease progression vignettes describing patients receiving cerliponase alfa consistently assigned higher utility values disease state suggesting treatment improves hrqol compared standard caretrial registration nct01907087 nct02485899,0.0
interoception primes emotional processing multimodal evidence neurodegeneration recent frameworks cognitive neuroscience behavioral neurology underscore interoceptive priors core modulators negative emotions however field lacks experimental designs manipulating priming emotions via interoception exploring multimodal signatures neurodegenerative models designed novel task involves interoceptive controlexteroceptive priming conditions followed postinteroception postexteroception facial emotion recognition fer recruited 114 participants including healthy controls hcs well patients behavioral variant frontotemporal dementia bvftd parkinson9s disease pd alzheimer9s disease ad measured online eeg modulations heartevoked potential hep associations brain structural restingstate functional connectivity patterns behaviorally postinteroception negative fer enhanced hcs selectively disrupted bvftd pd ad presenting generalized disruptions across emotion types bvftd presented impaired interoceptive accuracy increased hep modulations postinteroception negative fer observed hcs ad bvftd pd patients across groups postinteroception negative fer correlated volume insula acc also negative fer associated functional connectivity along salience network postinteroception condition along b executive network postexteroception condition patterns selectively disrupted bvftd pd b respectively approach underscores multidimensional impact interoception emotion revealing specific pathophysiological marker bvftd findings inform promising theoretical clinical agenda fields nteroception emotion allostasis neurodegenerationsignificance statement examined whether emotions primed interoceptive states combining multimodal measures healthy controls neurodegenerative models controls negative emotion recognition ongoing hep modulations increased interoception patterns selectively disrupted patients atrophy across key interoceptiveemotional regions eg insula cingulate frontotemporal dementia frontostriatal networks parkinson9s disease whereas persons alzheimer9s disease presented generalized emotional processing abnormalities preserved interoceptive mechanisms integration domains associated volume connectivity salience network canonical interoceptiveemotional hubs critically involving insula anterior cingulate study reveals multimodal markers interoceptiveemotional priming laying groundwork new agendas cognitive neuroscience behavioral neurology,0.0
idiopathic myelitis presenting brownsquard syndrome two case reports review theliterature background brownsquard syndrome often occurs spinal cord injury myelitis patients present brownsquard syndromecase presentationa 33yearold han man admitted neck pain plus numbness right limbs 2 days weakness left limbs 1 day examination significant left limbs grade 4 muscle power positive left babinski sign diminished vibration sensation left limbs decreased pain right clavicle dermatome cerebrospinal fluid csf cell count 24 106 l protein count 185 mg l cervical magnetic resonance imaging mri indicated abnormal swelling signals medullacervical cord long segment enhanced signals c23 region second case 47yearold han woman admitted weakness right lower limb numbness left lower limb 20 days examination significant right lower limb grade 4 muscle power left knee hyperreflexia positive left babinski sign diminished vibration sensation right lower limb decreased pain right t2 dermatome cervical mri indicated hyperintense enhanced signals c7t2 region two cases csf culture oligoclonal band ob aquaporin 4 aqp4 antibody negative brain mri normal symptoms mri results improved treatment methylprednisoloneconclusionsmyelitis can present brownsquard syndrome providing extended reference terms differential diagnosis clinical physicians,0.0
genomic pathological characterization multiple renal cell carcinoma regions patient tuberous sclerosis complex case report front oncol 2021 may 12 11691996 doi 103389 fonc2021691996 ecollection 2021abstracttuberous sclerosis complex genetic disorder characterized facial angiofibromas intellectual disability epilepsy tumor formation multiple organs including kidney renal cell carcinoma occurs 24 patients tuberous sclerosis complex often developing multiply bilaterally renal cell carcinoma associated genetic disorder may include complex tumor heterogeneity caused spatially different mutational landscape herein report case female patient tuberous sclerosis complex developed multiple renal tumors 44yearold female patient tuberous sclerosis complex developed three different histological types tumorangiomyolipoma clear cell renal cell carcinoma papillary renal cell carcinomain left kidney first renal cell carcinoma recurrence papillary renal cell carcinoma morphologically atypical indicating occurrence associated genetic disorder furthermore wholeexome sequencing revealed distinct patterns somatic mutation three tumor types atypical papillary renal cell carcinoma possessed different mutational landscape typical papillary renal cell carcinomas findings indicate tumors associated tuberous sclerosis complex may diagnosed careful pathological examination furthermore somatic mutation profiles tumors revealed unique features providing important information understanding mechanism multiple tumor development patients tuberous sclerosis complexpmid34055654 pmcpmc8149899 doi103389 fonc2021691996,0.0
progesterone dampens immune responsesinin vitroactivated cd4+t cellsand affects genes associated autoimmune diseasesthat improve pregnancy front immunol 2021 may 12 12672168 doi 103389 fimmu2021672168 ecollection 2021abstractthe changes progesterone p4 levels pregnancy coincide temporary improvement worsening several autoimmune diseases like multiple sclerosis ms rheumatoid arthritis ra likely immuneendocrine interactions play major role pregnancyinduced effects study used next generation sequencing investigate direct effects p4 cd4+ t cell activation key event pregnancy disease report profound dampening effects p4 t cell activation altering gene protein expression profile reversing many changes induced activation transcriptomic changes induced p4 significantly enriched genes associated diseases known modulated pregnancy ms ra psoriasis stat1 stat3 significantly downregulated p4 downstream targets significantly enriched among diseaseassociated genes several genes included wellknown diseaserelevant cytokines il12 cxcl10 osm validated also protein level using proximity extension assay results extend previous knowledge p4 immune regulatory hormone support importance pregnancy regulating potentially detrimental immune responses towards semiallogenic fetus results also point toward potential role p4 pregnancyinduced disease immunomodulation highlight need studies evaluating p4 future treatment optionpmid34054852 pmcpmc8149943 doi103389 fimmu2021672168,0.0
pharmacological modulators small gtpases rho family neurodegenerative diseases front cell neurosci 2021 may 12 15661612 doi 103389 fncel2021661612 ecollection 2021abstractclassical rho gtpases including rhoa rac1 cdc42 members ras small gtpase superfamily play essential roles variety cellular functions rho gtpase signaling can turned specific gefs gaps respectively features empower rho gtpases upstream downstream modulators targets scientific research therapeutic intervention specifically significant therapeutic potential exists targeting rho gtpases neurodegenerative diseases due widespread cellular activity alterations neural tissues study will explore roles rho gtpases neurodegenerative diseases focus applications pharmacological modulators recent discoveries exciting developments small molecules nonsteroidal antiinflammatory drugs nsaids natural products toxins classical rho gtpase category brief overview category followed examples applications will provided literature roles various diseases eg alzheimers disease ad parkinsons disease pd amyotrophic lateral sclerosis als frontotemporal dementia ftd multiple sclerosis ms highlights unique broad implications targeting rho gtpases potential therapeutic intervention clearly increasing knowledge therapeutic promise discovery pharmacological modulators rho gtpases managing treating conditions progress also accompanied recognition complex rho gtpase modulation targeting signaling can improve aspects pathogenesis exacerbating others disease model future directions emphasize importance elucidating different rho gtpases work concert produce widespread yet different cellular responses neurodegenerative disease progressionpmid34054432 pmcpmc8149604 doi103389 fncel2021661612,0.0
targeted blood brain barrier opening focused ultrasound induces focal macrophage microglial activation experimental autoimmune encephalomyelitis front neurosci 2021 may 12 15665722 doi 103389 fnins2021665722 ecollection 2021abstractexperimental autoimmune encephalomyelitis eae model multiple sclerosis ms eae reflects important histopathological hallmarks dissemination diversity disease moderate reproducibility clinical histopathological features focal lesions less frequently observed eae ms can neither constrained specific locations timed occur prespecified moment renders difficult experimental assessment pathogenesis lesion evolution including inflammatory degenerative demyelination axonal degeneration reparatory remyelination axonal sprouting gliosis component processes sought develop controlled model inflammatory focal brain lesions eae using focused ultrasound fus hypothesized fus induced focal blood brain barrier disruption bbbd will increase likelihood transmigration effector cells subsequent lesion occurrence sonicated location lesion development monitored conventional magnetic resonance imaging mri well magnetic resonance elastography mre analyzed histopathological means eae induced 12 68 weeks old female c57bl 6 mice using myelin oligodendrocyte glycoprotein mog peptide fusinduced bbbd performed 6 7 9 days immunization subgroups four animals additional control group mri mre performed 7t horizontal bore small animal mri scanner imaging conducted longitudinally 2 3 weeks disease induction 1 week sonication control animals respectively scan protocol comprised contrastenhanced t1weighted t2weighted sequences well mre vibration frequency 1 khz animals sacrificed histopathology last imaging time point overall clinical course eae mild total seven eae animals presented focal t2w hyperintense signal alterations sonicated hemisphere frequent group animals sonicated 9 days immunization histopathology revealed foci activated microglia macrophages sonicated right hemisphere seven eae animals larger cellular infiltrates apparent demyelination seen control animals showed abnormalities mri clusters activated microglia macrophages sites targeted fus none animals hemorrhages gross tissue damage potential side effects fus eaeanimals tended lower values viscoelasticity elasticity sonicated compared contralateral parenchyma trend significant comparing right sonicated left normal hemisphere specifically right sonicated compared left normal cortex animals underwent fusbbbd 9 days immunization right vs left hemisphere mean viscoelasticity 61 vs 72 kpa p 0003 mean elasticity 49 vs 57 kpa p 0024 right vs left cortex mean viscoelasticity 58 vs 75 kpa p 0004 mean elasticity 5 vs 65 kpa p 0008 direct comparison biomechanical properties focal t2w hyperintensities normal appearing brain tissue yield significant results control animals showed differences viscoelasticity sonicated contralateral brain parenchyma provide first evidence controlled lesion induction model eae using fusinduced bbbd observed lesions eae consistent foci activated microglia may interpreted targeted initial inflammatory activity described preactive lesions ms foci can identified monitored mri moreover increased inflammatory activity sonicated brain parenchyma seems effect overall tissue matrix structure reflected changes biomechanical parameterspmid34054415 pmcpmc8149750 doi103389 fnins2021665722,1.0
degree astrocyte activation predictive incubation time prion disease abstractin neurodegenerative diseases including alzheimers parkinsons prion diseases astrocytes acquire diseaseassociated reactive phenotypes growing appreciation role chronic neurodegeneration questions whether astrocytes lose ability perform homeostatic functions reactive states whether reactive phenotypes neurotoxic neuroprotective remain unsettled current work examined regionspecific changes expression genes report astrocyte physiological functions reactive states c57black 6j mice challenged four prion strains via two inoculation routes unexpectedly strong reverse correlation incubation time diseases degree astrocyte activation along disturbance functional pathways observed animal groups severe astrocyte response degree activation showed rapid disease progression degree activation tightly intertwined global transformation homeostatic state characterized disturbances multiple gene sets responsible normal physiological functions producing neurotoxic reactive phenotype net result neurotoxic reactive phenotype exhibited universal gene signature regardless prion strain current work suggests degree astrocyte activation along disturbance physiological pathways contribute faster progression disease perhaps even drive prion pathogenesis,1.0
stem cell therapies benefaction somatic cell nuclear transfer cloning covid19 era background global health emergency covid19 necessitated development multiple therapeutic modalities including vaccinations antivirals antiinflammatory cytoimmunotherapies etc covid19 patients suffer damage various organs vascular structures present multiple health crises mesenchymal stem cells mscs interest treat acute respiratory distress syndrome ards caused sarscov2 infectionmain bodystem cellbased therapies verified prospective benefits copious preclinical clinical studies mscs confer potential benefits develop various cell types organoids studying virushuman interaction drug testing regenerative medicine immunomodulatory effects covid19 patients apart paving ways augment stem cell research therapies somatic cell nuclear transfer scnt holds unique ability wide range health applications patientspecific isogenic cells regenerative medicine breeding transgenic animals biomedical applications potent cell genomereprogramming tool scnt increased prominence recombinant therapeutics cellular medicine current era covid19 scnt used generate patientspecific stem cells avoids dependence embryos obtain stem cellsconclusionsthe nuclear transfer cloning ideal tool generate cloned embryos embryonic stem cells will boost drug testing cellular medicine covid19,0.0
study comparing patient clinician perspectives treatments multiple sclerosis via group concept mapping patient prefer adherence 2021 may 12 15975987 doi 102147 ppas297052 ecollection 2021abstractbackground clinicians treating multiple sclerosis ms consider patient preferences making treatment decisions online mixedmethods approach elicit patientcentered concepts group concept mapping gcm used generate statements reflecting patient experience relapsingremitting ms identify important patientcentered outcomes patient clinician perspectivespatients methods twenty patients 12 ms specialists united states provided statements describing ideal treatment improve symptoms daily functioning statements sorted participants meaningful domains rated importance 11point scaleresults sixtyfour unique statements supporting 6 domains clustered concepts generated patient clinician ratings importance highly correlated r082 however patients rated domains activities daily living prevent cure address symptoms highest importance whereas clinicians rated prevent cure safe effective activities daily living highest importance statements rated domain mean patients clinicians included improve cognitive function improve motor function activities daily living domain help memory issues help preserve cognition address symptoms domain statement improve short term memory 1 3 statements rated domain mean patients domain mean cliniciansconclusion high levels agreement concept importance found patients ms specialists although certain domains statements rated highly one group overall concepts cognitive function physical emotional functioning activities daily living perceived great importance treatment outcomes versus symptomfocused outcomes like gait tingling sensations comprehensive concept model ms patient experience can used development patientcentered outcome measures ms treatmentpmid34012257 pmcpmc8126969 doi102147 ppas297052,0.0
retraction highdose omega3 fatty acid plus vitamin d3 supplementation affects clinical symptoms metabolic status patients multiple sclerosis randomized controlled clinical trial j nutr 2018 148 8 13806 j nutr 2021 may 11 151 5 1362 doi 101093 jn nxab074no abstractpmid33974700 doi101093 jn nxab074,0.0
abstracts 4th annual student medical summit a01 audit frequent attenders cork university hospital emergency departmentemer dight1 conor deasy21school medicine university college cork co cork ireland 2emergency department cork university hospital co cork irelandcorrespondence emer dightbackgroundin recent decades overcrowding hospitals become major issue ireland emergency department nature walkin attendees put increasing pressure frequent attenders fa shown increased mortality rates compared nonfrequent attenders nfa 1 primary aim audit profile cork university hospitals cuh emergency department ed fas describe prevalence fa also compared nfa possible fa defined patient attends five times per annummaterials methodsa retrospective audit cuhs 358 fas 1st january 31st december 2019 completed nfa also analysed comparative purposes data recorded microsoft excel data collected included arrival date age time spent department discharge destination preliminary diagnosisresultsapproximately 011 patients accounted 57 attendances 2019 358 patients presented total 2 565 times emergency department number visits per patients ranged 5 68 average number visits per patient seven mean age 56 years 47 fa female 53 male 40 fa visits ambulance compared 30 nfas fas discharged ward receive care 43 cases nfa went ward 29 fas top presenting complaint unwell adult 47 fa attendances due mental illness compared 075 nfaconclusionthis audit first kind done analysing cuhs fa studies required examine measures reduce fa attendance appropriate reduce risk adverse outcomes vulnerable groupacknowledgmentsthis audit completed without aid supervisor prof conor deasy bryan lynch cuh ed administration department assisting gathering datareference1 davison boyle hayhurst c 44 quantifying 5 year mortality frequent attenders emergency department emerg med j internet 2017 dec 1 cited 2020 december 12 34 12 a88990a02 survey compliance hse paediatric anaesthesia model care irish hospitals local audit paediatric anaesthesia outcomesciara walsh1 john chandler21school medicine university college cork cork ireland 2department anaesthesia university hospital cork cork irelandcorrespondence ciara walshbackgroundin 2015 hse released paediatric anaesthesia model care pamoc provides framework governance paediatric anaesthesia ireland document outlines recommendations pertaining facilities training structure paediatric anaesthesia service aims improve patient outcomes postoperative nausea vomiting unplanned admissions fasting times 1 thus far research investigating implementation pamoc study sought document uptake pamoc nonspecialist irish public hospitals assess anaesthesiologists attitudes towards model carematerials methodsall public hospitals republic ireland providing paediatric anaesthesia service excluding specialist centres operated childrens health ireland invited participate study anonymous survey requesting information regarding facilities training structure paediatric anaesthesia service sent via email assess compliance model careanonymized data random sample 10 children aged 15 general anaesthesia 2018 cork university hospital provided hospital inpatient enquiry top performance indicators set pamoc collected compared international standards included fasting times postoperative nausea vomiting unplanned admission daycase surgeryresults16 departments responded survey response rate 57 representing model 3 model 4 hospitals overall 9375 felt model care meaningfully changed influenced practice department 50 hospitals lead paediatric anaesthesiologist 31 lead paediatric anaesthesiologists undertake paediatric list weekly terms quality improvement 12 75 departments routinely recording performance indicators paediatric anaesthesia65 patients included audit mean fasting time sample 12 hours postoperative nausea vomiting identified 97 sample unplanned admission rate 18 comparison specialities children undergoing orthopaedic surgery significantly likely unplanned admission p0003 73 unplanned admissions orthopaedic casesconclusionsthis study indicates pamoc effectively implemented nonspecialist irish public hospitals comparatively high fasting times 2 unplanned admissions 3 highlighting area future study quality improvement deliver best quality anaesthesia care children irelandreferences1 hse model care paediatric anaesthesia 20152 thomas m morrison c newton r schindler e consensus statement clear fluids fasting elective pediatric general anesthesia pediatric anesthesia 2018 28 5 4114143 royal college anaesthetists raising standard compendium audit recipes section 5 day surgery services section 9 paediatrics 3rd edition 2012a03 functionalized selfassembling hydrogel treatment osteoarthritis partial thickness defect cartilagealiz gourrege1 baichuan wang1 2 hana alruzaiqi1 zhidao xia11centre nanohealth ils2 swansea university medical school swansea sa2 8pp uk 2department orthopaedics union hospital tongji medical college huazhong university science technology wuhan 430022 chinacorrespondence aliz gourrege zhidao xiabackgroundcartilage tough flexible connective tissue made chondrocytes synthesize turn components extracellular matrix 1 role weight bearing act cushion shock absorber bones 2 today 25 million people worldwide suffer cartilage defect 3 damaged cartilage unlikely selfheal due avascular nature passive diffusion cells matrix 2 actual treatments cartilage damage including medication physiotherapy surgery allow complete cure tissue often seen clinically cost expensive patient therefore need new treatments promote regeneration cartilage healthy state instead solely focusing relieving symptoms tissue engineering appears like promising option uses functional scaffolds recruit endogenous chondrocytes vivo site injury 4 materials methodsin study new functionalized peptide hydrogel named ragf designed enriching bio scaffold puramatrix rada16 platelet derived growth factor pdgf hypothesized ragf better promote proliferation cell viability chondrocytes compared rada16 alone chondrocytes isolated cultured femoral condyle bovine knee joints 5 6 proliferation tests performed using rada16 control measurements taken day 1 3 7 results analysed anova test determine difference ragf rada16 finally cytotoxicity test completed using three different dyes namely calcein acetoxymethyl calcein propidium iodide ip nucblue 7 number cells counted manually based images obtained fluorescence microscopy calculation percent viabilityresultspdgf significantly increased proliferation chondrocytes vitro figure 1 increase proliferation cell viability seen ragf statistically significant compared rada16 alone figure 2 3 conclusionsragf shows potential bio scaffold however indepth research longer periods time required properly evaluate benefits hydrogel articular cartilage regenerationfuture work include effect ragf chondrocytes migration differentiation expression chondrogenic related genes vitro well vivo regenerative capacity ragf induced cartilage defectacknowledgementsi like express sincere gratitude supervisor dr zhidao xia substantially guided research project without valuable advices help writing paper achieved also like thank leader project dr baichuan wang invaluable knowledge experience regenerative medicine kept right track journey technical intellectual contributions xiao li hana alruzaiqi ground laboratory manipulations added quality projectreferences1 akkiraju h nohe role chondrocytes cartilage formation progression osteoarthritis cartilage regeneration journal developmental biology 2015 3 4 1771922 sophia fox bedi rodeo s basic science articular cartilage structure composition function sports health multidisciplinary approach 2009 1 6 4614683 damage w cartilage damage patient education internet patient education 2021 cited 8 january 2021 available https cartilageorg patient aboutcartilage whatiscartilagedamage 4 tissue engineering regenerative medicine internet nibibnihgov 2021 cited 8 january 2021 available https wwwnibibnihgov scienceeducation sciencetopics tissueengineeringandregenerativemedicine5 vedicherla s buckley c rapid chondrocyte isolation tissue engineering applications effect enzyme concentration temporal exposure matrix forming capacity nasal derived chondrocytes biomed research international 2017 20171126 human chondrocytes hc culture protocol internet sigmaaldrich 2021 cited 2021 jan 8 available https wwwsigmaaldrichcom technicaldocuments protocols biology humanchondrocyteshtml7 live dead viability cytotoxicity kit mammalian cells internet 2005 dec cited 2021 jan 8 available http toolsthermofishercom content sfs manuals mp03224pdffig 1 abstract a03 figure1measurements absorbance concentration pdgf alone day 1 day 3 day 7full size imagefig 2 abstract a03 figure2absorbance rada16 ragf function timefull size imagefig 3 abstract a03 figure3fluorescent microscope images articular cartilage cells incubated rada16 ragf stained calcein nucblue pifull size imagea04 educational studies examining knowledge substance use disorders career aspirations among medical trainees innercity hospitalluke gooding1 micheeana hamilton2 huiru dong2 evan wood2 3 walter cullen1 nadia fairbairn2 3 seonaid nolan2 jan klimas2 41school medicine university college dublin health sciences centre belfield dublin 4 ireland 2british columbia centre substance use university british columbia 4001045 howe street vancouver bc canada 3department medicine university british columbia st pauls hospital 6081081 burrard street vancouver bc canada 4department family practice university british columbia david strangway building 5950 university blvd vancouver bc canadacorrespondence luke gooding lukegooding ucdconnectie backgroundgaps addiction medicine training reason poor substance use care north america 1 hospital addiction medicine consult services amcs provide critical medical services including screening treatment substance use disorders sud 2 programs often feature educational component medical learners impact amcs teaching objective knowledge career aspirations addiction medicine well describedmaterials methodswe report findings two sequential studies conducted large academic hospital vancouver canada first study assessed impact amcs clinical rotation medical trainee addiction medicine objective knowledge using online survey six true false questions rotation second study examined impact amcs rotation career aspirations using four sevenpoint likerttype questions onesample ttests mean differences md benjaminihochberg adjustment multiple comparisons employed statistical analysesresultsbetween may 2017 june 2018 knowledge scores significantly higher post rotation md 478 standard deviation sd 195 p 0034 among 115 medical traineesbetween july 2018 july 2019 aspirations pursue addiction medicine significantly favourable post rotation md 348 sd 315 p 0001 among 101 medical traineesconclusionamcs rotations appear improve addiction medicine knowledge aspirations pursue addiction medicine career among medical trainees largerscale evaluations outcomes research integrating sud teaching settings will help move discipline forwardacknowledgementsthe study supported us national institutes health r25da037756 research undertaken part thanks funding canada research chairs program tier 1 canada research chair inner city medicine supports dr evan wood project received funding european unions horizon 2020 research innovation programme marie skodowskacurie grant agreement 701698 seonaid nolan supported michael smith foundation health research university british columbias steven diamond professorship addiction care innovation nadia fairbairn supported msfhr st pauls foundation scholar awardreferences1 ayu ap schellekens af iskandar s pinxten l de jong ca effectiveness organization addiction medicine training across globe eur addict res 2015 21 5 223392 priest kc mccarty d role hospital 21st century opioid overdose epidemic addiction medicine consult service j addict med 2019 13 2 104112a05 systematic literature review identified articles evaluating positive margin re operation rate associated bcsvikneswaran raj1 swathica senthilkumar1 hemali chauhan2 daniel r leff31royal college surgeons school medicine 123 st stephens green d02 yn77 dublin ireland 2clinical research fellow department surgery cancer imperial college london st marys hospital south wharf road london w2 1ny 3reader breast surgery departments biosurgery surgical technology hamlyn centre robotic surgery imperial college london honorary consultant oncoplastic breast surgeon imperial college healthcare nhs trust st marys hospital south wharf road london w2 1nybackgroundbreast cancer common cancer women high incidence mortality rate uk ireland breast conserving surgery bcs frequently performed procedure treating women early stage breast cancer burden establishing positive margin real time emphasizes need accurate ima tool like iknife order establish burden positive margins systematic review carried systematic review evaluated effect dcis positive margin systematic literature review identified articles evaluating positive margin re operation rate associated bcs 1 inclusion exclusion criteria seen figure1materials methodsto start electronic search performed medline embase using specific search criteria using covidence two review authors independently screened title abstract studies identified search strategy studies screened included based criteria seen figure 1 clinical studies data bcs associated positive dcis margins leading reexcision incorporated remaining papers included subjected screening based final full text review papers full text review acquired using multiple sources papers obtained endnote software whilst rest still sourced reaching local libraries journal editors alongside finalising data extraction spreadsheet full text review complete data can extracted study incorporated spreadsheet spreadsheet drafted using different past metaanalysis similar nature study searched papers high impact factor publications ensure quality standard data extraction next step us discuss finalise spreadsheet final extraction factors deemed relevant ensure quality appraisal currently searching different quality scoring systems 2 successfully completed final step run metaanalysis combine highquality data extractedresultsa total 2 714 studies imported screening 577 duplicates removed leaving 2 137 studies screened using covidence studies filtered 1 876 studies found irrelevant satisfying set criteria remaining 261 papers subject full text screening next data extraction metaanalysis can carried conflicts discussed resolved review authors prisma model evidence based minimum set items reporting used seen figure 2 believe adhering primsa guidelines reduce potential bias may improve review quality 3 conclusionscurrently working final results systematic review now comment prevalence dcis found positive margin impact reexcision 4 5 hope gain fruitful insights systematic review completedreferences1 brouwer de koning sg vrancken peeters mjtfd jozwiak k bhairosing pa ruers tjm tumor resection margin definitions breastconserving surgery systematic review metaanalysis current literature clinical breast cancer 2018 18 4 e595e6002 bonell c jf harden et al systematic review effects schools school environment interventions health evidence mapping synthesis southampton uk nihr journals library 2013 jun public health research 11 appendix 6 data extraction quality appraisal tables available https wwwncbinlmnihgov books nbk262762 3 cullisps gudlaugsdottirk andrewsj systematic review quality conduct reporting systematic reviews metaanalyses paediatric surgery plos one 2017 12 4 e01752134 wei s kragel cp zhang k hameed o factors associated residual disease initial breast conserving surgery ductal carcinoma situ human pathology 2012 43 7 986935 houvenaeghel g lambaudie e bannier m rua s barrou j heinemann m et al positive close margins reoperation rate second conservative resection total mastectomy cancer management research 2019 11 piana department pathology paoli calmettes institute crcm cnrs inse rm marseille 13009 france 250716fig 1 abstract a05 figure4diagram listing inclusion exclusion criteria systematic reviewfull size imagefig 2 abstract a05 figure5diagram depicting workflow systematic review covidencefull size imagea06 diagnostic accuracy nipple discharge fluid cytology metaanalysis systematic review literatureswathica senthilkumar2 vikneswaran raj nagarajan2 natasha jiwa11department surgery cancer imperial college london st marys hospital south wharf road london w2 1ny 2royal college surgeons ireland 123 st stephens green d02 yn77 dublin irelandcorrespondence swathica senthilkumarbackgroundnipple discharge 3rd frequent complaint women attending rapid diagnostic breast clinics nipple smear cytology remains single utilised diagnostic modality investigation fluid content although diagnostic accuracy remains uncertain objective paper conduct systematic review metaanalysis diagnostic accuracy nipple discharge fluid assessmentmaterials methodsthis systematic review incorporated medline embase scopus databases searches studies interrogating diagnostic data nipple discharge fluid cytology compared histopathology gold standard data studies published 1956 2019 analysed analysis included 8 648 cytology samples 59 991 women hierarchical bivariate models diagnostic metaanalysis utilised attain overall pooled sensitivity specificity subgroup analysis diagnostic potential blood discharge fluid well imaging modalities conductedresultsof 837 studies retrieved fortyfive studies fulfilled criteria review metaanalysis analysis included 8 648 cytology samples diagnostic accuracy metaanalysis nipple discharge fluid illustrated sensitivity 75 95 ci 074077 specificity 87 95 ci 086087 benign breast disease sensitivity 62 95 ci 053071 specificity 71 95 ci 057081 breast cancer furthermore patients presenting bloodstained discharge yielded overall malignancy rate 58 054060 positive predictive value ppv 27 95 ci 017036 pooled ultrasound sensitivity specificity 70 060080 58 95 ci 024091 mammography sensitivity specificity 38 95 ci 023052 79 95 ci 069090 mri sensitivity specificity 70 95 ci 061070 045 95 ci 020070 conclusionspooled data studies encompassing nipple discharge fluid assessment suggests nipple smear cytology limited diagnostic accuracy moreover patients nipple discharge presenting symptom individual imaging modality high enough diagnostic accuracy exclude carcinoma recommendation tailored approach diagnosis required given variable sensitivities current available testsa07 differentiation lineage alters cytoskeletal epigenetic response mesenchymal stem cells tensile strainchris glynn1 stephen d thorpe21ucd school mechanical materials engineering university college dublin dublin ireland 2ucd school medicine ucd conway institute biomolecular biomedical research university college dublin dublin irelandcorrespondence chris glynnbackgroundmesenchymal stem cells mscs widely used connective tissue regenerative therapies application external mechanical forces mscs can initiate drive fibrochondrogenic differentiation associated epigenetic modification histone 3 lysine 27 trimethylation h3k27me3 affiliated heterochromatin formation 1 2 aim study investigate differentiationdependent changes cytoskeletal organisation nuclear shape response 2d dynamic uniaxial tensile strainmaterials methodsmscs subjected uniaxial tensile strain 3 1 hz 6 hours per day repeated daily 3 days media encourage osteogenic om adipogenic fibrochondrogenic differentiation alongside control basal media bm explore role transforming growth factor3 beta tgf3 mechanically driven fibrochondrogenic differentiation media cm+ without cm tgf3 used fluorescently labelled cell images figure 1 processed using custom matlab script assess filamentous f actin orientation alignment nucleus shape orientation h3k27me3 factin intensity pixel intensities within nucleusresultsuniaxial dynamic tensile strain led alignment factin nuclei direction perpendicular direction stretch basal osteogenic chondrogenic media tgf3 occur adipogenic chondrogenic media without tgf3the correlation actin fibre nuclei orientation increased strain application basal media dropped strain chondrogenic media without tgf indicates potential disconnect nucleus cytoskeleton strained chondrogenic mscs figure 2 lack realignment chondrogenic media without tgf compared media tgf observed along significant increase factin intensity significant reduction h3k27me3 intensity stretch suggests tgf necessary functional response stretchthe combination strain differentiation induction led reduction h3k27me3 intensity conditions p 005 conclusiondifferentiation alters response strain studying trilineage differentiation mesenchymal stem cells see high dependence strain response lineage suggesting interplay biochemical signalling mechanical signallingfuture work will investigate changing nature cytoskeletalnucleus connectivity chondrogenic differentiation provides potential active mechanism whereby cell regulates strain transfer nucleusreferences1 thorpe sd lee da dynamic regulation nuclear architecture mechanicsa rheostatic role nucleus tailoring cellular mechanosensitivity nucleus 2017 8 3 287300 doi101080 19491034201712859882 heo sj driscoll tp thorpe sd et al differentiation alters stem cell nuclear architecture mechanics mechanosensitivity elife 2016 doi 107554 elife18207fig 1 abstract a07 figure6representative staining across media different strainsfull size imagefig 2 abstract a07 figure7rose plots actin nucleus orientation across media range angles converted 180 90 demonstrate contrast stretch directionfull size imagea08 impact wide local excision sentinel node biopsy outcomes patients melanoma age 70kirsten carpenter1 2 stephanie m bollard1 2 3 christine s quinlan1 robert caulfield1 richard p hanson1 dylan j murray1 kevin cronin1 shirley m potter1 2 41department plastic reconstructive surgery mater misericordiae university hospital eccles street dublin 7 dublin ireland 2school medicine university college dublin belfield dublin 4 dublin ireland 3charles institute dermatology university college dublin belfield dublin 4 dublin ireland 4mater melanoma group mater misericordiae university hospital eccles street dublin 7 dublin irelandcorrespondence kirsten carpenterbackgroundthe incidence melanoma increasing elderly population 1 prevalent comorbidities must considered perioperatively despite significant developments adjuvant therapy space surgery form wide local excision wle + sentinel lymph node biopsy slnb remains cornerstone treatment primary melanoma study aims determine age associated comorbid factors influence surgical decisionmaking subsequent outcomes melanoma patients age 70 yearsmaterials methodsdata collected retrospectively melanoma patients age 70 treated single tertiary referral centre 10 years demographics comorbidities diagnosis surgical management details diseasefree dfs overall survival os tabulated impact age comorbidities analysedresultsa total 107 patients met inclusion criteria median age 7933 range 7096 years median breslow thickness 145mm range 00222 excisional biopsy performed 15 n16 85 n91 progressing wle patients underwent wle displayed increased dfs p0003 impact os p0716 significantly younger excisional biopsy p0003 eligible slnb n41 537 n22 underwent procedure note slnb significant impact dfs p0633 os p0222 conclusionsin elderly melanoma patient cohort wle resulted improved dfs effect os elderly melanoma patients suitable surgical candidates wle offered possible effort reduce morbidity recurrent diseaseacknowledgementsi like thank mater misericordiae university hospital department plastics reconstructive surgery guidance throughout stages researchreference1 whiteman dc green ac olsen cm growing burden invasive melanoma projections incidence rates numbers new cases six susceptible populations 2031 j invest dermatol 2016 136 6 11611171a09 infantile spasms trisomy 21 10 year review treatment approaches outcomes irelandkate flynn1 2 susan harvey 1 cian leahy 1 mohamed el hassan3 jibran aziz4 caroline kehoe5 donncha hanrahan6 sandya tirupathi6 sally ann lynch2 7 mary d king1 2 niamh lynch8 elizabeth omahony9 niamh mcsweeney4 olivia omahony4 nicholas m allen5 10 john c mchugh2 david webb3 mary oregan3 amre shahwan1 declan orourke1 2 brian lynch1 kathleen m gorman1 21department neurology clinical neurophysiology childrens health ireland temple street dublin ireland 2department neurology childrens health ireland crumlin dublin ireland 3department paediatrics bon secours hospital cork ireland 4department paediatrics university hospital limerick limerick ireland 5department paediatrics cork university hospital cork ireland 6department paediatrics galway university hospital galway ireland 7school medicine national university ireland galway galway ireland 8department neurology royal belfast hospital sick children belfast northern ireland 9school medicine medical science university college dublin dublin ireland 10national rare disease office mater hospital dublin dublin irelandcorrespondence kate flynnbackgroundtrisomy 21 t21 syndrome common chromosomal abnormality reported worldwide rate t21 ireland 1 411546 live births highest europe 1 infantile spasms occur 0613 t21 infants associated poorer neurodevelopmental outcomes increased risk epilepsy autism spectrum disorders 2 3 4 purpose review identify effective treatment options assist management t21 infantsmaterials methodsa multisite retrospective 10 year chart review performed inclusion criteria diagnosis t21 clinical presentation 2 years confirmation hypsarrhythmia modified hypsarrhythmia electroencephalogram eeg results54 infants eligible inclusion review median age onset based parental report 201 days iqr 156 2425 days median age presentation healthcare setting 239 days iqr 19153195 days initial eeg showed classical hypsarrhythmia 69 n37 modified hypsarrhythmia 31 n17 prescribed firstline medications prednisolone n20 vigabatrin n18 sodium valproate n9 combined prednisolone vigabatrin n6 acth n1 firstline medication achieved spasm cessation 44 n24 median two medications range 110 required achievement spasm cessationthe median length followup 30 months iqr 2449months spasm resolution occurred 85 infants n46 median time onset spasm cessation 110 days iqr 418196days commencing medication cessation 185 days iqr 381178days two children died ongoing seizures 24 13 54 cohort 40 20 54 antiepileptic medication developmental concerns 81medication sideeffects reported 17 infants vigabatrin associated 53 9 17 conclusionthis review largest cohort t21 patients n54 reported date spasm cessation can achieved 44 n24 treatment first medication monotherapy prednisolone frequently prescribed first line medication n20 achieving spasm cessation 60 12 20 medications well tolerated vigabatrin accounting majority side effects experienced 46 despite high rate spasm cessation developmental concerns 83 ongoing seizures 24 commonacknowledgementsi like thank dr kathleen gorman dr susan harvey neurology department chi temple street guidance support undertaking review preparation abstractreferences1 ni r filan mp trisomy 21 incidence outcomes first year ireland today imj 2014 107 8 2 stafstrom ce konkol rj infantile spasms children syndrome developmental medicine child neurology 1994 36 7 5765853 anderson t visootsak j tapp s neurodevelopmental outcomes children syndrome infantile spasms journal pediatric neurology 2015 13 02 0740774 sanmaneechai o sogawa y silver w ballabangil k mosh s shinnar s treatment outcomes west syndrome infants syndrome pediatric neurology 2013 48 1 4247a10 practices perspectives respect anticoagulation nonvalvular atrial fibrillation patients haemodialysisanna kelly1 sen leavey2 michelle m oshaughnessy3 ted fitzgerald21school medicine university college cork cork ireland 2department nephrology university hospital waterford waterford ireland 3 department renal medicine cork university hospital cork irelandcorrespondence anna kellybackgroundnonvalvular atrial fibrillation nvaf common cardiac arrhythmia can result ischaemic stroke 1 compared general population patients kidney failure receiving haemodialysis higher incidence nvaf stroke also major bleeding 2 studies examining risktobenefit ratio oral anticoagulation oac nvaf patients receiving haemodialysis produced inconclusive findings 3 investigated patient physician perspectives respect risks benefits oac nvaf patients receiving maintenance haemodialysismaterials methodswe screened patients scheduled attend two hospitalbased one communitybased dialysis clinic month october 2019 diagnosis nvaf collected demographic comorbidity dialysis prescription medication data identified cases patients interviewed regarding understanding nvaf associated stroke bleeding risks separately physician members irish nephrology society surveyed regarding perspectives nvaf management haemodialysis patients perceived riskbenefit oac six hypothetical cases ttest chisquare tests used univariate analyses twoway repeated measures anova used examine variation within across case vignettes respect perceived riskbenefit oacresultswe identified 41 patients 17 screened nvaf 18 44 patients prescribed oac 11 warfarin 7 apixiban oac use positively associated heart failure p001 higher bmi p001 cha2ds2vasc scores 3 p005 otherwise meanginful clinical differences statistically significant differences characteristics receiving vs receiving oac 27 surveyed patients reported awareness stroke risk nvaf 61 prescribed oac aware bleeding risk21 physicians responded survey response rate 178 uncertainty regarding nvaf management existed 90 asserting clinical equipoise surrounding oac therapy varying stroke bleeding falls risk 6 hypothetical cases significantly influence riskbenefit perceptions likelihood prescribe oac p001 however irrespective baseline riskbenefit perception physicians positively biased towards initiating oac biased towards continuing oac already prescribed p001 conclusionsa paucity evidence regarding relative risks benefits oac nvaf patients dialysis led inconsistent uncertain physician practice patterns urgent need randomized controlled trials oac nvaf patients dialysisreferences1 go hylek em phillips ka chang y henault le selby jv singer de prevalence diagnosed atrial fibrillation adults national implications rhythm management stroke prevention anticoagulation risk factors atrial fibrillation atria study jama 2001 285 18 237052 de vriese caluw r raggi p atrial fibrillation conundrum dialysis patients heart j 2016 17411193 van zyl m abdullah hm noseworthy pa siontis kc stroke prophylaxis patients atrial fibrillation endstage renal disease j clin med 2020 123115a11 children exploring impact covid19 related lockdown restrictions mental health presentations irish paediatric emergency departmentbrigid kemerer1 sarah casey2 ian mcclelland2 elizabeth barrett1 21ucd school medicine university college dublin belfield dublin 4 ireland 2department liaison psychiatry childrens health ireland temple street dublin 1 irelandcorrespondence elizabeth barrettbackgroundon march 12th 2020 irish government implemented disease containment measures due covid19 pandemic leading widespread social isolation school closures changes daily routine 1 older individuals considered risk physically evidence h1n1 sars epidemics showed approximately 330 quarantined children availed mental health services due anxiety adjustment disorders highlighting potential impact pandemic paediatric mental health 2 prospective study conducted exploring impact covid19 first national lockdown paediatric mental health presentations emergency department ed temple street childrens university hospital tscuh materials methodsed mental health presentations marchapril 2019 n79 2020 n60 reviewed multiple variables including reason presentation diagnosis presence selfharm sh suicidal intent prospectively gathered 2020 cases compared 2019 presentations descriptive analyses clinical findings using t tests chisquare tests oneway anova tests performed appropriate statistical significance considered p 005 ethical exemption granted chair local ethics committeeresultsed mental health presentations reduced 241 2020 proportional increase sh presentations +86 x2103 p031 reported suicidal intent +392 x21504 p0001 proportions representations ed increased 2020 noting 175 x2670 p001 increase previously presenting sh 436 x22588 p0001 increase previously presenting indications results show 76 rise attendance care settings children care settings presented tscuh ed april 2020 citing covid19 trigger ed presentation children presented family history sh +149 x2475 p 003 already prescribed psychotropic medication +307 x22331 p0001 attending psychotherapy 333 x21501 p0001 2020 221 increase ed presentations two diagnoses observed 2020 well changes factors precipitating ed attendance arguments family members +98 social isolation +72 school pressure 180 conclusionsour findings show fewer ed presentations lockdown present often high risk known services research needed explore reasons order proactively manage vulnerable individuals community effective service planningreferences1 irish times coronavirus affected ireland daybyday march 19 2020 available athttps wwwirishtimescom news health coronavirushowithasaffectedirelanddaybyday14206691 3 august 2020 2 sprang g silman m posttraumatic stress disorder parents youth healthrelated disasters disaster medicine public health preparedness 2013 7 1 105110a12 identifying sarscov2 transmission cluster category analysis country government databasebasem fouda1 2 ha pham bich tram2 3 omar mohamed makram2 4 5 abdelrahman sherif abdalla2 6 tushar singh1 2 ichun hung2 lina hemmeda2 7 majd alahmar2 8 akshay raut2 9 ahmed sallam elhawary2 10 dina awad2 11 nguyen tien huy12 131school medicine trinity college dublin ireland 2online research club nagasaki japan 3the vnuk institute research executive education university da nang da nang vietnam 4faculty medicine october 6 university giza egypt 5faculty public health policy london school hygiene tropical medicine london united kingdom 6faculty medicine elminia university elminya egypt 7faculty medicine university khartoum khartoum sudan 8faculty medicine mansoura university mansoura egypt 9rajarshee chhatrapati shahu maharaj government medical college kolhapur 41002 maharashtra india 10faculty medicine south valley university qena city egypt 11alexandria faculty medicine alexandria university alexandria egypt 12institute research development duy tan university da nang 550000 vietnam 13school tropical medicine global health nagasaki university 1124 sakamoto nagasaki 8528523 japancorrespondence basem fouda tushar singhauthors equally contributed work ie first 6 authors cofirst authors contributed research equally regards time effort dedicatedbackgroundthis study seeks identify settings prone transmission covid19 can provide insight regarding opening closure settings well monitoring testing result study can assist governments prioritizing control measures tackling possible future waves pandemic future pandemics similar naturematerials methodsfollowing comprehensive review relevant literature media articles extraction cluster data eight countries performed way hand searching reputable databases following data extracted arranged accessible online sheet total number clusters cases cluster type total number cases country date source data collection cluster types divided 10 main types subcategories specified types country 2 members assigned data validation reviewresultsamong eight included countries found 3905 clusters total number 1907974 patients indoor settings mass accommodation residential facilities comprised highest number number clusters 3313 3905 infected patients 1836870 1907974 outdoor ones comprised 592 clusters 71104 patients mass accommodation associated highest number cases 5 8 countries social events residential settings responsible highest number cases south korea malaysia respectively usa workplace facilities reported 165 clusters infection including 122 food production facilitiesconclusionsas lockdowns pose dilemma governments worldwide due widespread effects measures obtaining appropriate information concerning transmissibility behavior disease crucial order guide removal lockdowns across different fields regionsa13 crossreactivity conservation tcell epitopes across human coronavirusesjoseph j cronin1 damien farrell21ucd school medicine dublin ireland 2ucd school veterinary medicine dublin irelandbackgroundas covid19 pandemic continues dominate globe cause substantial mortality morbidity new research put spotlight tcell response sarscov2 particular scrutiny import placed suggested crossreactivity memory tcells specific commoncold coronavirus heterologous immunity sarscov2materials methodsusing epitope prediction software netmhcpan list likely mhcii epitopes cd4 tcells representing 8 common alleles generated sarscov2 spike protein following methods mateus et al netmhcpan configured predict 15mer epitopes core 9 amino acids conserved table 1 1 additionally sequence alignment spike protein genome viruses performed using jalview manually assess conservation literature review relevant papers tcell crossreactivity performed figure 1 resultsout 92 sarscov2 epitope predictions 2 epitopes conserved across board sars four commoncold coronaviruses 8 epitopes varying degrees conservation different computations 6 coronavirusesconclusionsthese conserved epitopes across human coronavirus family significant contribute growing body evidence human coronavirus memory tcells displaying heterologous immunity sarscov2 results underscore need research also results fit previous literature informs understanding immune response covid19 future therapeutic designs offers explanation variability symptoms covid19 symptoms 1 2 references1 mateus jose et al selective crossreactive sarscov2 t cell epitopes unexposed humans science aug 2020 sciencesciencemagorg doi101126 scienceabd38712 sekine takuya et al robust t cell immunity convalescent individuals asymptomatic mild covid19 biorxiv june 2020 p 20200629174888 wwwbiorxivorg doi101101 20200629174888table 1 abstract a13 top 12 predicted epitopes corresponding hcov homolog identityfull size tablefig 1 abstract a13 figure8sequence alignment s proteins hcovs performed jalviewfull size imagea14 pathogenicity helicobacter pylori parkinsons diseasekevin crishan1 justin mccarthy21school medicine university college cork cork ireland 2school biochemistry cell biology university college cork cork irelandcorrespondence kevin crishanbackgroundparkinsons disease pd second common neurodegenerative disease alzheimers disease exact etiology pd remains unclear 1 recent studies shown gi symptoms serve prodrome pd suggests helicobacter pylori may play role infection among pd patients detection eradication h pylori part current pd managementmethodsarticles selected medline embase databases according inclusion exclusion criteria metaanalysis prevalence h pylori infection pd relationship unified parkinsons disease rating scale updrs scores gut snca gene expression cases controls analyzed using odds ratios standardized mean differences smd 95 confidence intervals ci fixed randomeffects models applied statistical analyses performed review manager revman version 54 software suiteresultseleven studies included first metaanalysis 5039 pd cases 23194 controls h pylori infection prevalent pd patients 95 ci 146 126 168 pz 000001 five studies included updrs scores showed significant association h pylori infection mean updrs scores smd 95 ci 027 002 052 pz 003 snca gene expression also significantly higher among h pylori patients smd 95 ci 089 009 169 pz 003 conclusiona higher prevalence h pylori found among pd patients consistently lower updrs score among healthy controls shows increased risk among infected cohort worsens motor function furthermore significance snca expression gut biopsies h pylori infected patients suggests importance management pd potentially screening toolacknowledgementsthis work funded research postgraduate affairs committee uccreference1 tysnes o storstein epidemiology parkinsons disease journal neural transmission 2017 124 8 901905a15 harnessing artificial intelligence cardiac rehabilitation systematic reviewsara sotirakos1 basem fouda1 noor adeebah m razif1 cormac mulhall1 aisling obyrne1 bridget moran1 ruairi connolly1 21trinity college dublin school medicine dublin 2 ireland 2national rehabilitation hospital dublin irelandcorrespondence basem fouda bfouda tcdie backgroundclinical tools based artificial intelligence shown lot potential heart disease treatment diagnosis monitoring artificial intelligence ai defined concept machines can improved assume capabilities normally thought like human intelligence learning adapting selfcorrection etc 1 review explore ai currently utilised purpose cardiac rehabilitationmaterials methodsthe libraries pubmed medline embase cochrane scopus searched suitable papers using search terms heart disease artificial intelligence rehabilitation table 1 contains summary major inclusion exclusion criteriaresultsthe search returned 156 studies screening according inclusion criteria 8 studies included reviewsmart watchesmobile devices like apple watch fitbit charge hr 2 demonstrated potential health monitoring making earlier diagnosis enables prevention major adverse cardiac events therefore reduction hospitalization rateshomebased rehabilitation monitoringhomebased interventions consist homebased exercise protocols combination digital health system used delivering protocol patients report progress use tools can help patients lose weight improves body composition acting form secondary prevention 2 addition homebased cardiac rehabilitation programs can greatly improve accessibility patientsdecision making supportaibased technologies also potential aid physician patients ambiguous unclear symptoms use neurofuzzy model can offer doctors decisionmaking support comes prescribing different therapies 3 models can help reduce physician error therefore improve patient outcomesconclusionsai based technologies promising advancement field cardiac rehabilitation new demonstrated potential increase patients autonomy homebased interventions improve patient outcomes alerting seek timely medical care guide physicians decisionmaking processreferences1 kok jn boers e kosters wa van der putten p poel m artificial intelligence definition trends techniques cases artificial intelligence 2009 11202 widmer rj allison tg lennon r lopezjimenez f lerman lo lerman digital health intervention cardiac rehabilitation randomized controlled trial heart j 2017 18865723 obot ou uzoka fm akinyokun oc andy jj neurofuzzy decision support model therapy heart failure 2014 6 4 31944table 1 abstract a15 major inclusion exclusion criteriafull size tablea16 can collapse scalp hair follicle pigmentary unit age canities provide insights melanocyte death induced melanomahalin buruno1 daniel johnston1 2 desmond j tobin1 21ucd school medicine university college dublin belfield dublin 4 ireland 2ucd charles institute dermatology ucd school medicine belfield dublin 4 irelandcorrespondence halin burunobackgroundmelanoma potentially deadly skin cancer increasing incidence worldwide develops melanocytes located preferentially pigmented epidermis rather pigmented hair follicle hf epithelium 1 greying hfs aging follicular melanin unit associated increased melanocyte death apoptosis perhaps triggered uncontrolled oxidative stress os ataxia telangiectasia mutated atm protein kinase can sense dna damage os however activation mechanisms skin little understood 2 aimed investigate relationship melanocyte death greying hfs atm sensing osmaterials methodshuman haired scalp tissue n7 male 2573yrs mean46 440yrs ethically obtained charles institute via hair restoration blackrock tissue sections 510m cut double immunohistochemistry assay performed using melanocyte lineage marker nkibeteb antibodies atm phosphoatm images prepared using cellsense imagejresultsmelanocyte number decreased greying hfs pigmentation decreased figure 1 nuclear atm expressed hf bulbar melanocytes fibroblast cells dermal papilla hf bulb melanocytes superficial uv exposed epidermis figure 2 3 contrast phosphoatm expressed cytoplasmically keratinocytes epidermis upper hf figure 3 conclusionsresults confirmed melanocyte depletion human canitiesaffected hf also suggested protective role atm os hf bulbs retained pigmented melanocytes even significant age potential melanoma intervention strategy may modulate atm kinase expression melanoma cells make cells susceptible canitieslike deletion 1 2 acknowledgementsi like acknowledge opportunity time guidance given professor desmond tobin members charles institute dermatologyreferences1 bedogni b paus r hair y matters melanoma biology trends molecular medicine 2020 26 5 4414492 kozlov s graham m jakob b tobias f kijas tanuji m et al autophosphorylation atm activation journal biological chemistry 2010 286 11 91079119fig 1 abstract a16 figure9expression nkibeteb+atm melanocyte marker expression proportional melanin observed brightfield images hair follicle hf hair shaft hs hair bulb hb full size imagefig 2 abstract a16 figure10expression melanocyte marker nkibeteb+atm pigmented hair follicles increasing age hair follicle hf hair shaft hs hair bulb hb triangles melanocytes atm expression tissue tear t full size imagefig 3 abstract a16 figure11expression phosphoatm green atm red epidermis upper hf outer root sheathfull size imagea17 dux4c overexpression dysregulates pathways implicated facioscapulohumeral muscular dystrophy suggesting potential role pathogenesiscarter bagley1 darko bosnakovski2 micah d gearhart3 elizabeth t ener2 daniel chi2 michael kyba21ucd school medicine university college dublin belfield dublin ireland 2lillehei heart institute department pediatrics university minnesota minneapolis mn usa 3department genetics cell biology development university minnesota minneapolis mn usacorrespondence carter bagleybackgroundfacioscapulohumeral muscular dystrophy fshd genetic neuromuscular disease caused loss repression d4z4 repeat array 4q35 d4z4 repeat contains open reading frame encoding dux4 transcription factor cterminal transcriptional activation domain dux4c truncated inverted d4z4 element encoding protein identical dux4 except cterminus 82 amino acids replaced nonsense sequence dux4c expression inhibits myoblast differentiation downregulates myogenic regulators myod myf5 suggesting role fshd aim identify potential role dux4c fshd using bioinformatics analysis mouse muscle musclespecific doxycyclineinducible dux4c genematerials methodsrnaseq data obtained mouse muscle 2week induction doxycycline controls lacked either musclespecific rtta idux4c transgene differentially expressed genes degs identified analyzed r using bioconductor suiteresultsoverexpression dux4c dysregulates 3 513 genes 1 711 upregulated 1 802 downregulated padj005 comparison 2week dux4 overexpression showed 474 degs shared 229 commonly upregulated 202 commonly downregulated 43 oppositely regulated suggesting dux4c acts similar dux4 molecular level causing similar phenotype overexpressed 2 880 genes uniquely affected dux4c contributing pathways involving ca2+ homeostasis oxidative stress apoptosis dux4c overexpression dysregulates top 100 dux4 early target genes p0029 although expression changes weak compared dux4 example target myo1g induced approximately 15 dux4 foldchangeconclusionsdespite lacking transcriptional activation domain dux4c causes numerous transcriptional changes similar dux4 produces similar muscle pathology mice dux4c overexpression induces direct targets dux4 strongly suggesting much weaker transcriptional activity data coupled dux4cs dysregulation known fshd pathways gives cause research conducted determine extent action significance fshd humansa18 muscle wasting breast cancer model changes muscle fibre size mitochondrial dynamicsjacob lavieillecurran1 risn dwyer2 katarzyna whysall3 41school medicine national university ireland galway galway city galway ireland 2lambe institute translational research national university ireland galway galway city galway ireland 3department physiology school medicine national university ireland galway galway city galway ireland 4institute ageing chronic disease university liverpool liverpool merseyside united kingdomcorrespondence jacob lavieillecurranbackgroundcancer cachexia severe muscle wasting condition affecting 50 cancer patients 1 linked reduced treatment tolerance response increased morbidity mortality 2 exact mechanism cancer cachexia understood investigations crucial finding effective therapy mitochondria greatly affected catabolic conditions muscle loss 3 dysfunctional mitochondria can trigger catabolic signalling pathways causing muscle atrophy 3 project aims determine changes muscle mouse model breast cancer investigate potential associated mechanismsmaterials methodsthe gastrocnemius tibialis anterior isolated 3 control mice 3 tumourbearing mice muscles cryosectioned 8m fluorescently imaged 20x magnification fig 1 rna isolated used quantitative polymerase chain reaction establish changes expression mitochondrial atrophyrelated genesresultsno significant difference found muscle fibre sizes control mice mice cancer fig 2 significant decrease relative expression mitochondrial genes tomm20 mtnd1 observed tibialis anterior samples tumourbearing mice significant decrease relative expression mitochondrial genes coxiv opa1 also observed gastrocnemius samples tumourbearing miceconclusionthe weight tibialis anterior gastrocnemius muscles significantly reduced tumourbearing mice compared control mice however despite contrary findings human studies 2 muscle fibre diameter distribution show significant difference tumourbearing mice control mice potentially due detection challenges atrophic muscle fibres investigations using larger sample sizes different time points tumour induction necessary expression tomm20 mtnd1 reduced tibialis anterior muscle tumourbearing mice expression coxiv opa1 reduced gastrocnemius muscle tumourbearing mice changes may indicate cancer cachexias effect biogenesis mitochondria tomm20 oxidative phosphorylation process coxiv mtnd1 cellular atrophy mitochondrial stability opa1 within skeletal muscle may linked fibre typespecific changes processesacknowledgementsthis project funded national breast cancer research institute made possible help dr katarzyna goljanekwhysall golajnekwhysall lab dr risn dwyerreferences1 winje im sheng x hansson ka solbr tenne s saatcioglu f bruusgaard jc gundersen k cachexia induce loss myonuclei muscle fibres xenografted prostate cancer mice acta physiol 2019 225 3 2 johns n hatakeyama s stephens na degen m degen s frieauff w lambert c ross ja roubenoff r glass dj jacobi c fearon kc clinical classification cancer cachexia phenotypic correlates human skeletal muscle plos one 2014 9 1 3 romanello v sandri m mitochondrial quality control muscle mass maintenance front physiol 2016 6422fig 1 abstract a18 figure12mouse muscle fibre fluorescent microscopyfull size imagefig 2 abstract a18 figure13frequency distribution muscle fibre size tumourbearing micefull size imagea19 investigating macrophage activation response damageassociated molecular patterns multiple sclerosisdevika dahiya1 caitlyn joy loo1 jennifer dowling2 claire mccoy21school medicine faculty medicine health sciences royal college surgeons ireland 123 st stephens green d02 yn77 dublin ireland 2school pharmacy biomolecular sciences royal college surgeons ireland 123 st stephens green d02 yn77 dublin irelandcorrespondence devika dahiyabackgroundalthough cause multiple sclerosis ms unknown understand active macrophages release inflammatory mediators causing symptomatic damage however trigger macrophage activation unclear investigated damage associated molecular pattern highmobilitygroupbox 1 hmgb1 can trigger macrophage activation hmgb1 ubiquitous nuclear architectural protein found upregulated csf samples active plaques ms patients 1 materials methodswe measured hallmarks macrophage activation greiss assay il6 tnfand il1 elisa mir155 rtpcr raw 2647 bone marrowderived macrophages stimulated dose timedependent manner hmgb1 tolllike receptor agonist lps positive control experiments performed triplicate 4 independent timesresultsat 4 6 24 48 hrs lps 1 mg ml induced activation markers il6 tnfand il1 timedependent manner cell lines expected greatest lps 48 hrs hmgb1 alone 5 10 50 ng ml impact activation parameters however stimulated lps hmgb1 48 hrs statistically significant synergistic effect il6 tnfand il1 production raw2647 seenconclusionsour investigations imply hmgb1 can synergistically enhance inflammatory response lps stimulated macrophages impact hmgb1 later time points suggests may worsen chronic inflammation may relevant ms patients increased hmgb1 suffer chronic inflammation characterisation will explore different domains hmgb1 molecule macrophage activation well mechanism enhanced macrophage activation markersacknowledgementsresearch pi dr claire mccoyresearch supervisor dr jennifer dowlingresearch department school pharmacy biomolecular sciencesresearch partner caitlyn joy loorcsi research summer school dr sarah oneillfunding wellcome trustreference1 andersson covacu r sunnemark d danilov ai dal bianco khademi m wallstrm e lobell brundin l lassmann h harris ra pivotal advance hmgb1 expression active lesions human experimental multiple sclerosis journal leukocyte biology 2008 84 12481255 https doiorg 101189 jlb1207844a20 systematic review clinical presentation management covid19 associated multisystem inflammatory syndrome children misc marah shaikh yousef nur syazana idris charles yap abdulaziz abdullah alsubaie pramath kakodkarschool medicine national university ireland galway galway city republic irelandcorrespondence pramath kakodkarbackgroundfirstly collated vast repository misc cases presented simplified condensed comprehensive format secondly explored clinical presentation efficacy management options additionally briefly discussed pathophysiology addressed variance jargon criteria relating conditionmethodsa systematic literature review conducted 17th october 2020 accordance prisma 2015 guidelines search terms misc kawasakilike disease pimsts covid19 queried medline embase databases publications fulfilled inclusion criteria included assessed parameters pertaining clinical course managementresultsfrom december 2019 october 2020 131 publications identified 56 publications n646 patients fit inclusion criteria median age 10 years range 0517 years 522 n337 646 male 335 n128 382 african ethnicity sarscov2 reverse transcriptase pcr serology positive 42 n142 426 853 n300 352 cases respectively presenting complaint s predominately gastrointestinal 776 n436 562 generalized abdominal pain 764 n386 505 vomiting 632 n203 321 diarrhea hypotensive shock also commonly observed admission additionally laboratory data revealed elevated neutrophils inflammatory markers echocardiogram findings indicated reduced left ventricular ejection fraction myocarditis 226 n85 376 223 n84 376 cases respectively immunoglobulins intravenous steroids predominantly used 76 n433 571 51 n317 618 cases respectively majority patients 97 n418 431 discharged home combination treatment tocilizumab ivig mean length stay 73 days 955 n21 22 discharge rate low complications comparison either treatments aloneconclusionmics syndrome pediatric hyperinflammatory condition association covid19 background exposure misc heterogeneous multisystem presentation can associated life threatening cardiac complications need explore longterm morbiditya21 audit use brain biopsies nonneoplastic brain diseasesderry oflynn1 dr niamh bermingham21school medicine university college cork cork ireland 2department neuropathology cork university hospital cork irelandcorrespondence derry oflynnbackgroundin cases brain tumour seen neuroimaging brain biopsies gold standard method confirming diagnosis brain biopsies less predictable role investigation patients neurologic syndrome unknown aetiology neoplastic process suspected frequently performed setting brain biopsy tend last diagnostic resource disorders value procedure diagnosis well outcome management less welldefined aim study evaluate diagnostic yield safety brain biopsies performed single neurosciences centre clinically nonneoplastic brain diseases compare pathologic evaluation prebiopsy diagnosis analyse biopsy results significantly altered patient managementmaterials methodsthis retrospective study brain biopsies nonneoplastic brain diseases performed single neurosciences centre period 10 years cases identified using neuropathology reports cases excluded preoperative diagnosis clearly malignancy relationship preoperative presenting complaint laboratory testing neuroimaging management examined compared postbiopsy clinical outcome well management changesresultstwenty cases identified pathology reports sixteen twenty biopsies 80 pathologically diagnostic amyloid angiopathy common diagnosis 417 demyelinating disorder vasculopathy accounted 167 diagnoses made following biopsy results clinical management altered 80 patients introduction immunosuppressive agents common change occurring 438 154 patients clinical outcome recorded returned predisease baseline 462 patients recorded clinical outcome improved without returning predisease baseline complications rare impact overall outcomeconclusionsthis study shows brain biopsies appropriately performed useful high diagnostic yield even independently investigative modalities clinical outcome majority positive large proportion patients improving clinically complications rare impact patients overall outcome shows brain biopsies useful safe part diagnostic algorithm nonneoplastic neurological conditions uncertain ambiguous aetiology impact significantly patient managementa22 significance placental swab diagnosing vertical transmission sarscov2 positive mothersisabelle sweeney1 al assaf niazy2 khan rizwan21graduate entry medical school university limerick limerick ireland 2department neonatology university maternity hospital limerick limerick irelandcorrespondence isabelle sweeney sweeneyi tcdie backgroundcurrently limited date effects covid19 pregnancy neonatal outcome literature review aims investigate possibility fetal vertical transmission covid19 positive pregnant mothers diagnosing placental swabsmaterials methodsthe search terms pregnant covid19 positive mothers fetal vertical transmission placental swabs used 11 papers selected reviewresultsthis literature review comprises 45 covid19 positive pregnant women whose placentas neonates also analysed rtpcr presence sarscov2 43 neonates successfully delivered primarily via caesarean section 45 expectant mothers 96 2 mothers deliver due severe preeclampsia miscarriage occurring second trimester 3 neonates tested positive sarscov2 7 report neonatal mortality birth maternal mortality 8 females placentas tested positive sarscov2 total 45 tested 18 8 2 cases sarscov2 identified maternal neonatal placental tissueconclusionsafter reviewing multiple studies investigating nature placental physiology sarscov2 positive mothers conclude concrete evidence vertical transmission occurring mother infant however inconsistencies across different papers used review research investigating effects covid19 pregnant women using rtpcr test mother placenta vaginal fluid breast milk infant sarscov2 various stages transmission urgently neededa23 pain detectives optimizing management pain irritability children severe neurological impairmentketchum k1 11 hermansen am1 andrews g1 pawliuk c1 dewan t9 gnanakumar v10 orkin j4 5 richardson a1 vadeboncoeur c6 7 8 holsti l1 3 carleton b1 2 oberlander t1 2 siden h1 21british columbia childrens hospital research institute vancouver canada 2department pediatrics university british columbia vancouver canada 3department occupational science occupational therapy university british columbia vancouver canada 4department pediatrics university toronto toronto canada 5complex care hospital sick children toronto canada 6department pediatrics university ottawa ottawa canada 7childrens hospital eastern ontario ottawa canada 8roger neilson house ottawa canada 9department pediatrics university calgary calgary canada 10physical medicine rehabilitation alberta childrens hospital calgary canada 11medical student university college dublin dublin irelandcorrespondence ketchum k katherineketchum ucdconnectie backgroundchildren severe neurological impairment sni amongst vulnerable patients seen clinicians children sni typically nonverbal nonmobile cognitively impaired 1 many children experience pain demonstrate irritability daily basis 2 source discomfort difficult identify children unable communicate due complex nature sensations use term pain irritability unknown origin piuo describe believe lack standardized approach investigating managing piuo may contributing pain persistence suffering population address team developed systematic approach assessment pain patients sni piuo pathway termed incorporates structured historytaking physical examination screening investigations known occult sources pain pharmacological interventions goal efficiently assess treatable causes nociceptiveinflammatory painmethodswe used waitlistcontrolled randomized trial test efficacy piuo pathway participants randomized piuo pathway waitlist standard care arms pathway deemed success source nociceptiveinflammatory pain identified participant painfree low pain two consecutive visits secondary outcomes studied included decreased pain severity improved family quality life ease implementation piuo pathway cliniciansresultsthis trial ongoing preliminary results show 23 children completed piuo pathway four participants source pain identified treatment strategies children currently investigated seven participants piuo identified resolved recruiting will continue across four canadian research sites 120 participants completed pathway results secondary outcomes will assessed upon trial completion children source pain remains unidentified continue pain completion piuo pathway will eligible participate next trial prospective nof1 randomized controlled trial will investigate efficacy gabapentin relieving piuo children sniacknowledgmentsthe authors like thank participants families joining study research funded childbright network spor cihrtrial registration numberclinicaltrialsgov identifier nct03464773 piuo pathway trial clinicaltrialsgov identifier nct04619862 gabapentin trial references1 siden hb carleton bc oberlander tf physician variability treating pain irritability unknown origin children severe neurological impairment pain res manag j can pain soc j socit can pour trait douleur 2013 18 5 2432482 sthleberg l fjellmanwiklund parents experience pain children cerebral palsy multiple disabilities interview study adv physiother 2009 11 3 137144 doi101080 14038190902906318a24 pathway analysis splice variants suggest role inflammatory processes type 1 myotonic dystrophyiulia cornila jeffrey c glennonconway institute biomolecular biomedical research ucd school medicine belfield dublin 4 irelandcorrespondence iulia cornilabackgroundtype 1 myotonic dystrophy dm1 multisystem neuromuscular disease caused trinucleotide expansion dmpk gene results toxic gainoffunction activity rna leading myriad downstream splice variants aberrant proteins research will explore splice variants share common functionalities pathway interactionsmaterials methodsfrom existing published literature experimentally validated predicted splice variants dm1 analyzed using pathway analysis determine contribute common biological pathways total 83 predicted 55 experimentally validated splice variants dm1 examined using kegg mapper reactome databases statistics computed using reactome overrepresentation analysis microrna predicted regulate misspliced genes gathered using targetscanhuman pathway analysis also conducted order search common functionality two datasetsresultspredicted misspliced dm1 genes revealed strong pathway interactions responses innate adaptive immune system antigen processing presentation p111e16 endosome phagosome pathways p111e16 cytokine signalling p274e14 experimentally validated misspliced dm1 genes showed significant pathway interactions involving mecp2 regulation gene transcription p17e7 cardiac conduction p157e4 rtk signal transduction p226e3 platelet homeostasis p253e3 ion channel transport p279e3 integrin signalling p399e3 gene sets implicated pathways involved muscle contraction p505e4 myogenesis p00341 microrna analyses revealed significant pathway interactions immune system platelet homeostasis myogenesis muscle contraction axon guidance intracellular signal transductionconclusionspathway analysis dm1 variant genes regulatory microrna shows common functionality pathways prominently immune system operations eg interleukin interferon signalling lymphocyte activity especially present predicted misspliced gene set yet experimentally explored future studies confirm common pathways viable mechanisms intervention biomarkers prognosis disease severitya25 lower incidence preterm birth irish cohort congenital uterine anomalieslily farrell1 niamh keating2 siobhn corcoran21university college dublin dublin ireland 2preterm birth clinic national maternity hospital irelandcorrespondence lily farrellbackgroundglobally congenital uterine anomalies strong association increased risk adverse pregnancy outcomes including miscarriage 43 1 preterm birth 20 2 caesarean delivery 34 2 objective study examine obstetric outcomes women significant uterine anomalies national maternity hospital ireland nmh material methodsthis retrospective cohort study cases uterine anomalies pregnancy nmh 10 year period 2011present cases identified reviewing database nmhs preterm birth clinic women known uterine anomalies referred antenatal care within time frame 33 pregnancies amongst 19 women significant uterine anomaly defined unicornuate bicornuate didelphys septate uterus requiring resection without vaginal septumresultswithin study period 20112020 nmh reported 86 535 deliveries amongst 94 141 women women 19 000024 identified significant uterine anomaly ranged bicornuate uterus n9 474 uterine didelphys n5 263 resected uterine septum n2 105 uterine septum n1 53 unicornuate uterus n1 53 vaginal septum n4 211 cerclages preterm surveillance averaging 11 visits per pregnancy 32 livebirths table 1 one pregnancy remains ongoingconclusionsour study found notably lower preterm birth rate 31 amongst cohort women relative findings international studies rates high 397 recorded miscarriage rate 135 also lower comparable studies 429 caesarean delivery rate higher amongst cohort relative background population international findings however largely attributed elective sections due increased maternal age patient demand insights gained data will help us focus counselling specific population regarding pregnancy outcomes women uterine anomalies findings suggest area warrants national investigation recommend similar audit carried remaining irish maternity hospitals using methodology prove invaluable nationwide results differ significantly ours case key differentiating factors may identifiedreferences1 jayaprakasan k chan yy sur s deb s clewes js rainefenning nj prevalence uterine anomalies impact early pregnancy women conceiving assisted reproduction treatment ultrasound obstet gynecol 2011 jun 37 6 72732 doi 101002 uog8968 epub 2011 mar 30 pmid 213376622 meiling hua anthony o odibo ryan e longman george macones kimberly roehl alison g cahill congenital uterine anomalies adverse pregnancy outcomes american journal obstetrics gynecology volume 205 issue 6 2011 pages 558e1558e5 issn 00029378 https doiorg 101016 jajog201107022table 1 abstract a25 comparison study population versus general hospital obstetric outcomesfull size tablea26 frailty hospitalized patients upholding standard careanna m demian1 katherine coupland1 mingchih tsai2 joseph garvin2 niamh hannon31school medicine university limerick limerick ireland 2department general surgery portiuncula university hospital ballinasloe ireland 3department geriatric medicine galway university hospital galway irelandcorrespondence anna m demianbackgroundthe geriatric population defined age 65 years 1 patient population comprises 1415 irelands total population 53 inpatient hospital care 2 3 thus important health care professionals hcp identify frail need comprehensive geriatric care audit sought examine portiuncula university hospitals puh compliance health service executive hse guidelines states older adult patients identified frail risk frailty comprehensive geriatric assessment cga 1 materials methodsto assess congruence puh hse guidelines questionnaire distributed 131 puh hcp evaluating level awareness frailty confidence managing frail patients additionally 59 geriatric surgical patient charts reviewed assess puh adherence use standardized frailty tools appropriate referrals geriatric surgical patients admitted hospital next steps will include educating hcp reauditing 3 months afterresultsresults questionnaire showed discrepancy confidence reported 32 factual knowledge 68 frailty assessment amongst puh hcp figure 1 figure 2 results also showed hospital departments benefit formal education lastly based guidelines puh underutilizing frailty assessment tools referrals cgas 17 geriatric surgical inpatients appropriately referred 2 rockwood score 4 4at score completedconclusionthe results audit will help target future research tailor educational interventions evident results education needed hcp puh order maximize utilization standardized frailty assessments future goals establish database geriatric care puh research purposes expand database include departmentsreferences1 national clinical programme older people comprehensive geriatric assessment summary health service executive 2016 116 available https wwwhseie eng services publications clinicalstrategyandprogrammes comprehensivegeriatricassessmentsummarypdf accessed 26 june 20202 central statistics office census population 2016 profile 3 age profile ireland cso statistical publication 2017 available https wwwcsoie en releasesandpublications ep pcp3oy cp3 accessed 24 july 20203 department health health ireland key trends 2018 statistics analytics unit 2019 3647 available healthgovie accessed 24 july 2020fig 1 abstract a26 figure14average correct incorrect answers amongst puh hcp n 131 full size imagefig 2 abstract a26 figure15determining confidence puh hcp assessing frailty n 131 full size imagea27 appropriate nonvitamin k antagonist oral anticoagulant dosing nonvalvular atrial fibrillation patientsdebola shomoye debolasho yahooie school medicine university limerick garraun castletroy limerick irelandbackgroundatrial fibrillation af common clinical arrhythmia carrying approximate lifetime risk one four age 40 years 1 anticoagulation proven reduce afrelated mortality 2 inappropriate noac doses lead less favourable outcomes relation thromboembolic events death 3 project aims determine degree compliance nonvitamin k antagonist oral anticoagulant noac dosing standards implement computerised noac dosing aid reduce occurrence inappropriate noac dosing nonvalvular atrial fibrillation nvaf patientsmaterials methodsdata 100 living nvaf patients noacs captured completegp cgp software search utilised boolean operators variables interest patient age noac dosage frequency renal function body weight testing appropriate dosing calculated based information approved european union summary product characteristics spc results13 patients incorrect noac dose figures 12 14 patients baseline biochemical weight results prior initiation noac therapy moreover 44 undergone regular testing since commencing noac therapy total number patients drug cohort eligible standard doses 89 apixaban 88 rivaroxaban 100 edoxaban 100 dabigatran patients appropriately received standard doses underdosing form inappropriate dosing patients rivaroxaban n3 18 patients eligible receive standard daily dose apixaban prescribed reduced dose n8 represented 73 apixaban inappropriate dosing meanwhile 125 rivaroxaban patients eligible standard dose prescribed reduced dose computerised dosing aid designed improve compliance dosing recommendations prompt prescribers arrange renal function bodyweight testing reminders nvaf patients figures 3 4 conclusioninappropriate noac dosing prevalent general practice detrimental patient health compliance noac dosing standards af patients can optimised utilising computerised dosing aid formal reminder systemsreferences1 lloydjones dm wang tj leip ep larson mg levy d vasan rs dagostino rb massaro jm beiser wolf pa benjamin ej lifetime risk development atrial fibrillation framingham heart study circulation 2004 110104262 wolf pa abbott rd kannel wb atrial fibrillation independent risk factor stroke framingham study stroke 1991 2298383 steinberg ba shrader p pieper k thomas l allen la ansell j chan ps ezekowitz md fonarow gc freeman jv gersh bj frequency outcomes reduced dose nonvitamin k antagonist anticoagulants results orbitaf ii outcomes registry better informed treatment atrial fibrillation ii journal american heart association 2018 7e007633fig 1 abstract a27 figure16noac dose appropriatenessfull size imagefig 2 abstract a27 figure17characteristics inappropriate dosingfull size imagefig 3 abstract a27 figure18sample entry cgp computerised noac dosing aidfull size imagefig 4 abstract a27 figure19preview cgp computerised noac dosing aidfull size imagea28 designing ehealth portal patient voice cancer research promote public patient involvement research across academic patient communitiesaoife gordon1 david gomez2 tom hope2 walter kolch1 teresa mcnally2 idn n sh4 mary staunton2 tina osullivan2 antoinette perry5 romina silva2 husvinee sudaramurthi3 ramon whelan2 amanda mccann1 2 elaine quinn21ucd school medicine university college dublin belfield dublin 4 2patient voice cancer research pvcr ucd conway institute biomolecular biomedical research university college dublin belfield dublin 4 3ucd school biomolecular biomedical sciences ucd conway institute university college dublin belfield dublin 4 4ucd school nursing midwifery health systems university college dublin belfield dublin 4 5school biology environmental science science west obrien science centre university college dublin belfield dublin 4backgroundthe patient voice cancer research pvcr grew unmet need involve voices cancer patients families scientific research process bring pvcr line public patient involvement ppi initiatives internationally dedicated engaging website drafted vital communication toolmaterials methodsa literature review international ppi websites canada europe uk attendance annual ppi summer school university limerick undertaken consent form interview questions pvcr committee members designed interviews conducted cancer patients 6 researchers 5 develop 11 informative reflective profiles national adult literacy agency guidance sought concerning requirements obtaining plain english mark line international standardsresultsthe profiles transcripts reviewed permission granted use pvcr website social media manuscript peer review entitled give us idea paper documents pvcr journey initiation involvement nationally prepared journal research involvement engagementconclusionsthe pvcr paving new path ppi cancer research ireland research included assimilating reflective insight motivation impact pvcr membership since initiation 2016 ii vision patients researchers ppi importance advancing cancer research crucial aspects pvcr websiteacknowledgementthe authors like acknowledge project possible without patient voice cancer research pvcr committee members cancer researchers within ucd conway institute systems biology ireland sbi a29 benefit adjuvant therapy patients undergone neoadjuvant therapy oesophageal adenocarcinomashantam agarwal1 yuriy dovhan1 diane doran1 ciara owens1 magdalina fadel1 diana williams1 claire donohoe21school medicine trinity college dublin dublin 2 ireland 2department surgery trinity college dublin dublin 2 irelandcorrespondence shantam agarwal agarwash tcdie backgroundoesophageal adenocarcinoma oac aggressive cancer worse prognosis advanced stage disease 1 standard treatment locally advanced oesophageal cancer neoadjuvant chemoradiation followed surgery trimodal regimen 2 role postoperative treatment unclear 2 study aims review benefits adjuvant therapy postoperative periodmethodswe carried review 8 papers using following databases pubmed embase clinical trialsgov cochrane set determine hazard ratio average 3year 5year overall survival percentages patients underwent neoadjuvant adjuvant therapyresultswe identified total 16 299 patients cohort 1712 underwent adjuvant therapy experimental arm remaining 14 587 treated control arm 15 reduction death hr 085 inclusion adjuvant therapy average 5year os 384 experimental arm comparison control arm 338 p value 042 average 3year os 509 experimental arm 459 control arm p value 044 additionally 30 26 20 reduction risk death observed node positive oac patients burt et al 2017 eng et al 2018 nevalaplagemann et al 2018 randomized controlled trials respectivelyconclusionalthough considerable benefit seen inclusion therapy trimodal regimen use across range disease presentations present statistically significant benefit context 3 5year overall survival rates nevertheless promising finding reduced risk death statistically significant observed residual nodal disease cohort trial dispenses great opportunity considerable research conducted area definitively conclude incorporated typical treatment regime thus combat high mortality rate associated diseasereferences1 pennathur gibson mk jobe ba luketich jd oesophageal carcinoma lancet 2013 381 9864 400122 ajani ja damico ta bentrem dj chao j corvera c das p et al esophageal esophagogastric junction cancers version 22019 nccn clinical practice guidelines oncology journal national comprehensive cancer network 2019 17 7 85583 eng o nelson r konstantinidis chao j erhunmwunsee l raz d et al disparities survival trimodality therapy esophageal adenocarcinoma diseases esophagus 2018 31 9 3 burt bm groth ss sada yh farjah f cornwell l sugarbaker dj et al utility adjuvant chemotherapy neoadjuvant chemoradiation esophagectomy esophageal cancer annals surgery 2017 266 2 2973044 eng os nelson ra konstantinidis chao j erhunmwunsee l raz dj et al disparities survival trimodality therapy esophageal adenocarcinoma diseases esophagus 2018 31 9 5 nevalaplagemann c francis s cavalieri c tao r whisenant j glasgow r et al benefit adjuvant chemotherapy based lymph node involvement oesophageal cancer following trimodality therapy esmo open 2018 3 5 a30 road traffic collision related injuries national rehabilitation hospital 5year retrospective reviewaisling okeeffe1 ine carroll1 21school medicine university college dublin ireland 2academic department national rehabilitation hospital dublin irelandcorrespondence aisling okeeffe aislingokeeffe ucdconnectie backgroundthe road safety authority rsa came 1 september 2006 statutory organisation created road safety authority act 2006 aim reduce collisions deaths injuries since number deaths roads reduced according major trauma audit mta national reports many surviving road traffic collisions life altering injuries decided undertake review see presentations national rehabilitation hospital nrh road traffic trauma related injury changedmethodsretrospective review healthcare records tertiary rehabilitation hospital patients discharged inpatient rehabilitation service icd 10 coded diagnosis transport accidents v00 v899 transport accidentrelated injury 20142018 includedresults338 cases identified 179 meet inclusion criteria due record duplication miscodingthe total number healthcare records analysed systematically using standardised proforma 159109 68 male 50 32 female 115 72 40 years age 122 77 traumatic brain injuries 32 20 traumatic spinal cord injuries 4 25 traumatic amputation combined injuries overall reduction rtc related injuries 4 years studied numbers varied year overall trend apparentconclusionthe number admissions national rehabilitation hospital road traffic collision related injury reduced course 5 years review remains elevated linking data mta nrh admission information may effective way better understand impact rsa strategy policyacknowledgementsthe authors grateful coding staff national rehabilitation hospital assistance projecta31 patients admitted icu sarscov2 infection dexamethasone superior standard care improving mortality systematic review evidence datelaith al azawi1 conor farrell1 lauren hayes1 liam mariga1 imad mirza1 mariam salem1 carmel kennedy21school medicine trinity college dublin dublin 2 ireland 2department pharmacology therapeutics st jamess hospital dublin irelandcorrespondence laith al azawibackgrounddexamethasone potent broadspectrum corticosteroid decreases transcription pro inflammatory cytokines whilst simultaneously increasing transcription antiinflammatory cytokines cytokine storm central pathogenesis acute respiratory distress syndrome ards multi organ failure seen severe acute respiratory syndrome coronavirus 2 sarscov2 related deaths objective study appraise current evidence use dexamethasone treatment patients admitted intensive care unit icu sarscov2 infectionmaterials methodswe conducted searches two databases embase pubmed using terms covid19 dexamethasone icu search limited english language publications human clinical trials prisma flow chart used guide search methodologyresultsthe database search identified 59 articles two duplicates discarded 57 citations screened 54 publications deemed irrelevant based inclusion exclusion criteria three forwarded full text review met inclusion exclusion criteria fulltext review three deemed eligible selected studies consisted two randomised clinical trials rcts one case series report results three papers unanimous conclusion dexamethasone superior standard care treatment patients admitted icu sars cov2 also shorter duration hospitalisation seen patient group treated dexamethasoneconclusionsour systematic review found dexamethasone superior standard care alone patients admitted icu sarscov2 infection however administration dexamethasone patients respiratory support resulted higher incidence death compared standard care alonea32 investigating effects substrate stiffness biodegradable polymers astrocyte physiologysen kerr1 cian oconnor2 adrian dervan2 maeve caldwell31school medicine university college dublin belfield dublin 4 ireland 2tissue engineering research group department anatomy royal college surgeons ireland 123 st stephens green dublin 2 ireland 3trinity college institute neuroscience department physiology trinity college dublin dublin irelandcorrespondence sen kerrbackgroundastrocytes nonneuronal supportive cells play number diverse roles healthy central nervous system cns following spinal cord injury astrocytes become reactive characterized altered gene expression morphology 1 form glial scar around lesion 2 glial scar contributes tissue softening altered extracellular matrix ecm deposition cns interestingly stiffness ecm composition shown affect astrocyte reactivity 3 however effect substrate stiffness astrocytes yet well understood increasing use biotherapeutic implantable devices led heightened interest reaction cells implant properties stiffness therefore characterization reaction astrocytes substrates varying stiffness critical factor consider design implantable therapeutic devices use cnsmethodswe aimed create 3d hyaluronic acid hya scaffold tuneable stiffness however hya requires trophic ecm proteins support cell attachment first cultured astrocytes coverslips various ecm components assess effects astrocyte physiology via immunocytochemistry fluorescence microscopy imagej software manufactured hya scaffolds using 3 concentrations 3 5 10mg ml stiffness assessed mechanical testing pore size characterized toluidine blue staining microscopy cultured astrocytes scaffolds varying stiffness assessed metabolic activity via alamar blue assays expression reactivity associated proteins via elisa across multiple timepointsresultsastrocyte metabolic activity significantly altered assessed ecm components however actin outgrowth cell area significantly increased astrocytes cultured ecm1 ecm1+2 nuclearcytoplasm area gfap intensity basic metrics astrocyte reactivity significantly altered group manufacture scaffolds tuneable stiffness successful 3mg ml scaffolds significantly softer 10mg ml scaffolds pore size significantly higher 3 5mg ml scaffolds compared 10mg ml scaffolds metabolic activity astrocytes cultured scaffolds initially decreased d1d4 remained consistent later timepoints d4d21 3mg ml scaffold displayed greatest activity d21 secretion il6 astrocytes significantly decreased groups d1 onwards detectable levels d21 quantification actin gfap coverage revealed softer scaffolds significantly greater coverage actin gfapconclusionsthe substrate stiffness hya scaffolds significant effects astrocyte physiology significant implications scaffold designreferences1 sofroniew mv molecular dissection reactive astrogliosis glial scar formation trends neurosci 2009 32 12 638472 cregg jm depaul ma filous ar lang bt tran silver j functional regeneration beyond glial scar exp neurol 2014 2531972073 moeendarbary e weber ip sheridan gk koser de soleman s haenzi b et al soft mechanical signature glial scars central nervous system nat commun 2017 814787a33 prolonged response metastatic pancreatic cancer treated pembrolizumab based mismatch repair status characterized next generation sequencinglan d ngo1 2 ana c garridocastro2 melissa e hughes2 nancy u lin21ucd school medicine university college dublin belfield dublin 4 ireland 2danafarber cancer institute 450 brookline ave boston ma 02215 usabackgroundmetastatic pancreatic cancer associated poor prognosis standard regimens including gemcitabine nabpaclitaxel folfirinox 1year survival 10 1 patients metastatic tumors progress standard treatment microsatellite instabilityhigh msih mismatch repairdeficient mmrd tumors potential candidates pembrolizumab pd1 immune checkpoint inhibitor frequency msih mmrd tumors 2 pancreatic adenocarcinomas compared 17 endometrial 6 colorectal cancers 2 msi mmr status traditionally determined using immunohistochemistry ihc pcr testing patients danafarber cancer institute approached oncopanel testing targeted nextgeneration sequencing ngs platform primary metastatic tumor tissue using validated bioinformatics algorithm msi mmr status can inferred oncopanel data 3 present case report patient metastatic pancreatic cancer identified msih mmrd using oncopanelcase reporta 71yearold female presented abdominal back pain palpable left supraclavicular mass pet imaging revealed pancreatic mass enlarged retroperitoneal supraclavicular nodes supraclavicular node biopsy confirmed metastatic pancreatic adenocarcinoma genetic testing confirmed lynch syndrome patient treated folfox progression 5 months gemcitabine nabpaclitaxel progression 2 months oncopanel testing showed msih mmrd confirmatory ihc pancreatic mass revealed absent msh2 staining consistent mmrd patient initiated pembrolizumab continued treatment 16 months recent scan showing responseconclusionthis case illustrates prolonged clinical benefit pd1 inhibition patient metastatic msih mmrd pancreatic cancer refractory standard chemotherapy cancer types low frequency msih mmrd institutionwide ngs platforms can leveraged costeffective method identify mmrd msih potential candidates immunotherapyconsent publishpatients danafarber cancer institute approached consent cancer research study oncopanel tumor testing participant provided written informed consent consent publicationreferences1 azar virk g esfandiarifard s et al treatment survival rates stage iv pancreatic cancer va hospitals nationwide study j gastrointest oncol 2019 10 4 7037112 le dt durham nj smith nk wang h bartlett br aulakh lk et al mismatchrepair deficiency predicts response solid tumors pd1 blockade science 2017 357 6349 4094133 nowak ja yurgelun mb bruce jl et al detection mismatch repair deficiency microsatellite instability colorectal adenocarcinoma targeted nextgeneration sequencing j mol diagn 198491 2017a34 vaccines age skepticism pandemicjonathan l jeger1 thomas drago1 mark wadid1 sean garvey1 kirolos bassily2 john hanna31school medicine trinity college dublin dublin ireland 2midlands regional hospital portlaoise ireland 3sligo university hospital sligo irelandcorrespondence jonathan l jeger jegerj tcdie joint firstauthorshipbackgroundvaccination first discovered 1796 edward jenner effort prevent spread smallpox disease 1 2 smallpox vaccine described successful vaccination effort human history administered 150 years world health organization declared disease eradicated 1980 3 4 5 1998 study wakefield et al reported possible causal relationship measlesmumpsrubella vaccination autism 12 children uk resulting antiimmunization lobby receiving considerable media attention 6 7 although publication retracted 2010 controversy surrounding vaccination lasting impact 8 covid19 cases still increasing throughout ireland rest world covid19 vaccination options horizon find ourselves important moment time take closer look vaccination antiimmunization lobbymaterials methodswe performed literature search regards covid19 vaccination options explored current vaccine trials data compared findings framework vaccine allocation prioritization outlined additionally also explored ethical question receive access vaccines firstresultsafter extensive review literature gathered information regarding importance vaccinations herd immunity strategic ways immunize large populations highlighting statistically significant results several vaccine candidates illustrated importance vaccination process safe effective way combat virus midst pandemic affecting nearly every nation worldwide careful research analysis study aims reduce skepticism vaccines also emphasize statistics highlight benefitsconclusionskepticism vaccine virus reaching ends globe profound issue seen countless nations growing concerns safety efficacy important delineate data emphasizing benefits multiple tested therapeutics order effectively combat pandemicreferences1 begg n nicoll myths medicine immunisation bmj 1994 309 6961 107310752 stewart aj devlin pm history smallpox vaccine journal infection 2006 52 5 3293343 maurer dm harrington bc lane mj smallpox vaccine contraindications administration adverse reactions american family physician 2003 68 5 8898964 henderson da inglesby tv bartlett jg ascher ms eitzen e jahrling pb hauer j layton m mcdade j osterholm mt otoole t smallpox biological weapon medical public health management jama 1999 281 22 212721375 world health organization global eradication smallpox final report global commission certification smallpox eradication internet geneva switzerland 1979 cited 2020 dec 1 available https appswhoint iris handle 10665 392536 wakefield aj murch sh anthony linnell j casson dm malik m berelowitz m dhillon ap thomson ma harvey p valentine retracted ileallymphoidnodular hyperplasia nonspecific colitis pervasive developmental disorder children lancet 1998 351 9103 6376417 burgess dc burgess ma leask j mmr vaccination autism controversy united kingdom 19982005 inevitable community outrage failure risk communication vaccine 2006 24 18 392139288 caplan al retractionileallymphoidnodular hyperplasia nonspecific colitis pervasive developmental disorder children weekly epidemiological record 2010 84301308a35 poststudy pointofcare oral fluid testing hiv1 vaccineskarina oganezova1 2 elvin j fontanamartinez2 jon gothing2 alisha pandit2 esther kwara3 katherine yanosick4 joan dragavon5 erin goecker5 janine maenza6 7 nicole espy6 frank tomaka8 ludo lavreys9 mary allen10 patricia dsouza10 john hural6 robert w coombs5 7 raphael dolin4 11 michael s seaman4 11 stephen r walsh2 11 lindsey r baden2 111school medicine trinity college dublin ireland 2division infectious diseases brigham womens hospital boston ma usa 3morehouse school medicine atlanta ga usa 4center virology vaccine research beth israel deaconess medical center boston ma usa 5department laboratory medicine university washington seattle wa usa 6vaccine infectious disease division fred hutchinson cancer research center seattle wa usa 7department medicine university washington seattle wa usa 8janssen pharmaceutical research development titusville nj usa 9janssen vaccines prevention bv leiden netherlands 10national institute allergy infectious diseases rockville md usa 11harvard medical school boston ma usacorrespondence karina oganezovabackgroundexperimental hiv1 vaccines frequently elicit antibodies hiv1 may react commonly used hiv diagnostic tests phenomenon known vaccineinduced seropositivity seroreactivity visp visr sought determine clinic conditions oraquick advance rapid hiv1 2 antibody test detect hiv1 vaccineinduced antibodiesmaterials methodsplasma assessment hiv1 crossreactivity examined endofstudy samples 57 healthy hivuninfected participants received candidate vaccine entered phase 2b 3 testing also screened 120 healthy hivuninfected unblinded hiv1 vaccine participants visp visr assessment using saliva participants came 21 different parent vaccine protocols representing 17 different vaccine regimens contained hiv1 envelope immunogen oraquick advance compared results concurrent blood samples using series commercial hiv screening immunoassaysresultsfiftyseven unique plasma samples vaccine recipients assayed vitro one 18 reactive oraquick advance table 1 none 120 clinic participants 0 95 ci 0 37 tested positive oraquick advance confirmed uninfected hiv1 viral rna testing 118 120 983 participants reactive hiv test visp visr 77 64 least one reactive fourthgeneration hiv1 diagnostic test p00001 vs reactive oraquick advance results 41 34 reactive test less specific thirdgeneration abbott prism assay p00001 vs reactive oraquick advance results table 2 conclusionsthese data suggest test limited reactivity hiv1 antibodies elicited candidate hiv1 vaccines related overthecounter patientcontrolled oraquick inhome test tested study may potentially provide similar results due limited sensitivity oraquick advance oraquick inhome hiv test detection acute hiv suggest tests continue paired comprehensive pretest posttest hiv counsellingtable 1 abstract a35 analysis oraquick advance crossreactivity plasma samples vaccine recipientsfull size tabletable 2 abstract a35 analysis oraquick advance saliva crossreactivity blood testsfull size tablea36 impact sarscov2 pandemic referral characteristics national tertiary spinal injuries unitlouis ohalloran1 daniel p ahern2 3 jake m mcdonnell4 michael k dodds3 frank lyons3 noelle cassidy 3 marcus timlin3 seamus morris3 keith synnott3 joseph s butler3 51school medicine university college dublin dublin ireland 2school medicine trinity college dublin dublin ireland 3national spinal injuries unit department trauma orthopaedic surgery mater misericordiae university hospital dublin ireland 4royal college surgeons ireland dublin ireland 5ucd clinical research centre ucd school medicine mater misericordiae university hospital dublin irelandconflict interest authors declare conflict interestbackgroundthe sarscov2 pandemic profound implications healthcare institutions aim study assess compare referral patterns covid19 corresponding dates preceding three years 20172019 order preemptively coordinate logistics surgical unit similar future experiencesmethodsa retrospective review carried institution national tertiary referral centre spine pathology two distinct timepoints chosen represent varied levels social restriction current pandemic study period 1 sp1 11 03 2008 06 20 represents national lockdown ii study period 2 sp2 09 06 2009 09 20 indicates easing restrictions periods compared corresponding dates cp1 11 0308 06 cp2 09 0609 09 preceding three years 20172019 data collected included age gender mechanism injury moi descriptive analyses mois categorised disc disease cyclist roadtrafficaccident rta falls 2m falls 2m malignancy sporting injuries miscellaneousresultsall moi categories witnessed reduction referral numbers sp1 disc disease 29 cyclist 5 rtas 66 falls 2m 39 falls 2m 17 malignancy 33 sporting injuries 100 miscellaneous 58 4 8 categories rtas falls 2m malignancy miscellaneous showed trend towards return prelockdown values sp2 two categories disc disease falls 2m showed reduction 34 27 sp2 one category sporting injuries portrayed complete return normal values sp2 notable increase cyclist related referrals witnessed +63 compared corresponding dates previous yearsconclusionspinal injury continues occur across almost categories albeit considerably reduced numbers rtas falls remained common mechanism injury awareness needs drawn reduction malignancy related referrals dissuade people symptoms avoiding presentation hospital periods social restrictionsa37 idiopathic intracranial hypertension anemia systematic review metaanalysis case seriesethan waisberg1 caberry w yu2 jonathan micieli31ucd school medicine university college dublin belfield dublin 4 ireland 2school medicine faculty health sciences queens university kingston ontario canada 3department ophthalmology vision sciences university toronto toronto ontario canadacorrespondence ethan waisbergbackgroundidiopathic intracranial hypertension iih defined elevated intracranial pressure absence identifiable cause relationship iih anemia remains controversial goal study report consecutive cases iih fulminant course severe anemia hemoglobin 80g l provide additional evidence topic study also aimed examine causal relationship anemia iihmaterials methodsthe retrospective case series four patients iih severe anemia diagnosed neurologic imaging lumbar puncture extensive workup exclude secondary causes medline embase cochrane library grey literature searched september 2020 primary studies patients diagnoses anemia kind iih included primary outcomes included total number cases anemia iih metaanalysis prevalence anemia iih compared control patients conductedresultsfour patients female included series average age 28 years mean body mass index 322kg m2 visual acuity ranged 20 20 20 50 average humphrey mean deviation 730db average hemoglobin presentation 71g l mcv 720 correction anemia required aggressive treatment intravenous iron two patients oral iron remaining cases patients also treated acetazolamide optic nerve sheath fenestration one patient patients resolution papilledema symptoms within 3 months hemoglobin increased normal levels timeoverall 74 cases 5 observational casecontrol studies included pooled incidence anemia iih patients 195 1073 182 iih patients n774 significantly higher prevalence anemia compared controls n230 981 rr 144 95 ci 108 192 reported patients 35 59 593 showed improvement resolution anemia treatment 7 59 119 intracranial pressurelowering therapy 15 59 254 bothconclusionsanemia 44 common iih compared control patients many case reports suggesting direct relationship complete blood count important workup patients presenting papilledema especially severe peripapillary cotton wool spots case series suggests direct relationship severe anemia fulminant iih patients severe anemia onset resolution symptoms papilledema normalization hemoglobina38 medical screening mental health emergenciesfouad helmy1 nigel salter21ucd school medicine belfield dublin 4 ireland 2emergency department st vincents university hospital elm park dublin 4 irelandcorrespondence fouad helmybackgroundmental health presentations account 5 emergency department ed attendance requires higher level resources often patients present acute crisis triggered life changing event necessitating multidisciplinary input causes management plan complex slow determining medical illness cause patients acute psychiatric symptoms always straightforward limited deescalation facilities ed can lead inefficiencies patient care despite currently limited literature flow patients ed psychiatric presentations pilot project aims analyse current practice medical assessments ed patients effects patient flowmethodspatients registered triaged clinical notes documented svuh ed system ims maxims data gathered 156 ed attendances 10week consecutive period investigations performed including bloods ecg ctbrain urine toxicology urine dipstick xray total ed visit duration figure 1 significant testing performedresults119 patients 763 total form investigations performed including bloods ecg xrays ctbrain urine toxicology urine dipstick percentage abnormal test results total amount tested urine dipstick urine toxicology tests 465 667 respectively contrast xrays ctbrain ecgs low percentage abnormal test results 125 769 26 respectively compared mean ed duration tests done noticed using kruskalwallis test significant difference mean ed duration urine toxicology p0005 ctbrain p0002 ecgs p0011 performed significance urine dipstick testing p0122 however compared mean ed duration abnormal results done urine dipstick tests using mannwhittney u test obtained p value 004 significantconclusionswe observed high rate investigations performed patients presenting psychiatric complaints high rate normal results tests also observed significantly longer duration ed stay patients xrays ecgs ctbrain performed strategies focused rationalising use investigations ed will optimise flow patient cohortfig 1 abstract a38 figure20frequency patients ed duration hours line shows normalfull size imagea39 retrospective study body mass index weight loss irish adults admitted acute hospital following infection sarscov2fiona newsome1 ciara murphy21university college dublin ireland 2st michaels hospital dun laoghaire dublin irelandcorrespondence fiona newsomebackgroundthe rapid spread virus sarscov2 hereafter covid19 resulted global pandemic march 2020 infections various complications lengthy hospital stays noted patients contracting covid19 weight loss malnutrition may predictors complications recovery infection also predictive increased length hospital stay 1 aim current study investigate potential associations body mass index bmi percentage weight loss length stay los complications experienced inpatient covid19materials methodsthis single centre cohort study involving adult patients diagnosed covid19 admitted acute general hospital ireland 1st march 2020 31st may 2020 data extracted relevant patient charts using standardised reporting form analysed using spss ibm spss version 260 resultsof 30 patients included study 29 discharged following recovery covid19 one fatality hospital stay 37 n11 patients suffered severe weight loss 10 n3 suffered moderate weight loss 13 n4 sustained mild weight loss 40 n12 weight loss mean percentage weight lost 291 median interquartile range 143 0166 significant relationship percentage weight loss los overall however patients noncomplex discharge n 20 significant positive linear correlation r 0516 p 002 found significant positive correlation percentage weight loss number complications recovery also observed overall r 0423 p 002 conclusionthere significant findings number complications experienced los based percentage weight loss suffered patients current study found larger deficit patients weight admission discharge greater potential complications lengthier hospital stays therefore results current study highlight need appropriate multidisciplinary management patients covid19 including targeted nutritional management hospital stay following discharge conclusion preventing weight loss malnutrition imperative patients hospitalised sarscov2 minimise risk complicationsreference1 casaer m van den berghe g nutrition acute phase critical illness n engl j med 2014 370 13 12271236a40 clinical significance burden thyroid nodules discovered incidentallyrohil dureja1 caoimhe casey2 josephine barry3 antoinette tuthill21school medicine university college cork cork ireland 2deperatment endocrinology cork university hospital cork ireland 3deperatment radiology cork university hospital cork irelandcorrespondence rohil durejabackgroundreporting thyroid incidentalomas ti imaging preformed indications led clinical dilemma majority thyroid nodules benign however current guidelines suggest ti worked rule malignancy study aims determine incidence tis likelihood reveal sinister pathology largest irish cohort studied datematerials methodsa retrospective observational chart review conducted using imaging studies obtained cork university hospital july 2018 december 2018 pacs database searched using defined inclusion exclusion criteria body summary 500 carotid dopplers 500 computed tomography ct thorax manually screened phrases thyroid mass thyroid nodule patients tis identified electronic records medical charts used track follow ups final outcome identified nodulesresultsout 1 000 scans 14 14 thyroid incidentalomas discovered average age tis according study 68 equal distribution seen amongst genders occurrence tis imaging 2 500 04 carotid doppler 12 500 24 ct thorax three 214 tis evaluated subsequent ultrasound three tis found 10cm underwent investigation fine needle aspiration using cytology tis given thy 2 grading nonneoplastic conclusionthis study found clinical benefit reporting presence tis discovered incidentally three tis evaluated found benign suggesting tis unlikely sinister pathology higher number tis discovered ct comparison us can explained lack formal guidelines reporting thyroids cts concern remains 98 tis expected found modalities year number may enough cause strain healthcare system addition workup tis burden patients invasive investigations cause unnecessary anxiety healtha41 repurposing psychological interventions healthcare workers covid19sean treacy1 tamara schloemer2 fiona mcnicholas3 john hayden41school medicine medical science university college dublin dublin ireland 2department international health faculty health medicine life sciences caphricare public health research institute maastricht university postbus 616 6200 md maastricht netherlands 3department child adolescent psychiatry school medicine medical science university college dublin dublin 4royal college surgeons ireland school pharmacy 111 st stephens green dublin irelandbackgroundthe covid19 pandemic shown large negative impact mental health healthcare workers evidencebased interventions used mitigate lacking literature systematic review aims evaluate psychological interventions used employees following disasters assess transferability interventions healthcare setting covid19 pandemicmaterials methodselectronic database embase searched 2015 2020 studies identified alongside studies received previous review 1 assessed transferability using checklist based piett process model 2 resultsan additional three studies identified updated literature search eighteen studies included assessment transferability interventions evaluated included psychological debriefing meditation courses cognitive behavioural therapy mental health training courses psychoeducation courses trauma risk management trim conclusionstrim improve help seeking behaviour healthcare workers meditation courses alleviate stress healthcare workers mental health training courses build resilience healthcare workers psychological debriefing potential negative effects recommended transfer research needs undertaken area assess transferability interventionsreferences1 brooks sk dunn r amlt r greenberg n rubin gj training postdisaster interventions psychological impacts disasterexposed employees systematic review j ment health 20181252 schloemer t schroderback p criteria evaluating transferability health interventions systematic review thematic synthesis implement sci 2018 13 1 88a42 efficacy ssris elderly depressionsalman omaruniversity limerick school medicine limerick irelandbackgrounddepression elderly can challenging treat known respond well pharmacotherapy selective serotonin reuptake inhibitors ssris prescribed antidepressants efficacy low side effect profile little known direct comparisons different ssris efficacy level primary outcome literature review assess data escitalopram citalopram fluoxetine sertraline determine one efficacious regarding treatment latelife depressionmaterials methodsthe literature search conducted using medline full text apapsycarticles apapsycinfo along keywords escitalopram citalopram sertraline fluoxetine depression elderly geriatric review includes studies looked efficacy ssris treatment depression elderly term elderly defined anyone aged 60 exclusion criteria includes studies mention efficacy look patients age 60 studies missing data also excluded efficacy identified using standardized depression scales hamilton depression scale hamd 1 geriatric depression scale gds 2 montgomeryasbergdepression scale madrs 3 relevant literature screened based abstracts titles articles read thoroughly references also searched find eligibility results literature search summarised figure 1resultsthe use citalopram elderly patients depression assessed 496 patients results summarised table 1 citalopram associated greater proportion remission greater daily dose hamd scores baseline significantly improved 4 escitalopram associated less positive response elderly patients major depression sertraline favored poorly compared antidepressants like fluvoxamine fluoxetine improved efficacy compared placebo similar efficacy compared amitriptylineconclusioncitalopram consistently showed improvement scores efficacy studies reviewed however data required direct comparisons ssris treatment depression elderly concrete conclusion can drawnreferences1 hamilton m rating scale depression journal neurology neurosurgery psychiatry 1960 23 1 pp56622 yesavage ja et al development validation geriatric depression screening scale preliminary report journal psychiatric research 1982 17 1 pp37493 montgomery sa asberg m new depression scale designed sensitive change 1979 134 4 pp3823894 lavretsky h et al citalopram methylphenidate combination geriatric depression randomized doubleblind placebocontrolled trial 2015 american journal psychiatry 172 6 pp5615695 kyle cj et al comparison tolerability efficacy citalopram amitriptyline elderly depressed patients treated general practice depression anxiety 8 4 pp1471536 navarro v et al citalopram versus nortriptyline latelife depression 12week randomized singleblind study 2001 acta psychiatrica scandinavica 103 6 pp4354407 allard p et al efficacy tolerability venlafaxine geriatric outpatients major depression doubleblind randomised 6month comparative trial citalopram 2004 international journal geriatric psychiatry 19 2 pp112311308 klysner r et al efficacy citalopram prevention recurrent depression elderly patients placebocontrolled study maintenance therapy 2002 british journal psychiatry journal medical science 181 1 pp2935fig 1 abstract a42 figure21prisma flow diagram created using http prismastatementorg prismastatement flowdiagramfull size imagetable 1 abstract a42 summary citalopram treatment elderly,1.0
bhmtbetaine methylation pathway epigenetically modulates oligodendrocyte maturation plos one 2021 may 11 16 5 e0250486 doi 101371 journalpone0250486 ecollection 2021abstractresearch epigenome growing importance loss epigenetic control implicated development neurodegenerative diseases previous studies implicated aberrant dna histone methylation multiple sclerosis ms disease pathogenesis previously reported methyl donor betaine depleted ms linked changes histone h3 trimethylation h3k4me3 neurons also shown betaine increases histone methyltransferase activity activating chromatin bound betaine homocysteine smethyltransferase bhmt investigated role bhmtbetaine methylation pathway oligodendrocytes immunocytochemistry human mo313 cell line primary rat oligodendrocytes tissue ms postmortem brain confirmed presence bhmt enzyme nucleus oligodendrocytes bhmt expression increased 2fold following oxidative insult qrtpcr demonstrated betaine can promote increase expression oligodendrocyte maturation genes sox10 nkx22 oxidative conditions chromatin fractionation provided evidence direct interaction bhmt chromatin coip analysis indicates interaction bhmt dnmt3a data show histone dna methyltransferase activity increased following betaine administration betaine effects shown dependent bhmt expression following sirna knockdown bhmt first report bhmt expression oligodendrocytes suggests betaine acts bhmt modulate histone dna methyltransferase activity chromatin data suggest methyl donor availability can impact epigenetic changes maturation oligodendrocytespmid33975330 doi101371 journalpone0250486,0.0
semaphorins adult nervous system plasticity disease front synaptic neurosci 2021 may 11 13672891 doi 103389 fnsyn2021672891 ecollection 2021abstractsemaphorins originally discovered guidance cues developing axons involved many processes shape nervous system development neuronal proliferation migration neuritogenesis synapse formation interestingly expression many semaphorins persists development instance semaphorin 3a component perineuronal nets extracellular matrix structures enwrapping certain types neurons adult cns contribute closure critical period plasticity semaphorin 3g 4c play crucial role control adult hippocampal connectivity memory processes semaphorin 5a 7a regulate adult neurogenesis evidence points role semaphorins regulation adult neuronal plasticity review address distribution semaphorins adult nervous system discuss function physiological pathological processespmid34045951 pmcpmc8148045 doi103389 fnsyn2021672891,0.0
genebased tests genomewide association study dataset highlight novel multiple sclerosis risk genes front neurosci 2021 may 11 15614528 doi 103389 fnins2021614528 ecollection 2021abstractmultiple sclerosis ms autoimmune disorder influenced genetic environmental factors many studies provided insights genetic factors contribution ms via largescale genomewide association study gwas datasets however genetic variants identified date adequately explain genetic risks ms study hypothesized novel ms risk genes identified analyzing msgwas dataset using genebased tests analyzed gwas dataset consisting 9 772 ms cases 17 376 healthy controls european descent performed genebased tests 464 357 autosomal single nucleotide polymorphisms snps using two methods plink vegas2 identified 28 shared genes satisfied pvalue 456 106 gene expression analysis ten 28 genes significantly differentially expressed ms casecontrol gene expression omnibus geo database galc hladob showed prominent differences gene expression two threefold respectively ms patients healthy controls conclusion results reveal information ms hereditary characteristics provide basis studiespmid34045940 pmcpmc8144314 doi103389 fnins2021614528,0.0
fucoidan promising agent brain injury neurodegenerative disease intervention food funct 2021 apr 16 doi 101039 d0fo03153d online ahead printabstractbrain injury neurodegenerative diseases alzheimers disease parkinsons disease amyotrophic lateral sclerosis urgent medical problems severely threaten life quality patients carers however currently effective therapies fucoidan natural compound found brown algae animals multiple biological pharmacological activities antioxidant antitumor anticoagulant antithrombotic immunoregulatory antiviral antiinflammatory effects growing number studies shown fucoidan also exerts neuroprotective function particularly recent findings indicated fucoidan slow neurodegenerative processes show protective effects brain injury might therapeutic value intervening brain injury neurodegenerative diseases review discussed pharmacokinetics fucoidan well molecular mechanisms fucoidan exerts neuroprotective effect neurological disorders along also summarized potential benefits fucoidan combination drugs treatment neurodegenerative diseases brain injury although extraction process fucoidan improved well efforts devoted translational research clinical trials fucoidan near futurepmid33861265 doi101039 d0fo03153d,1.0
4ethylguaiacol modulates neuroinflammation th1 th17 differentiation ameliorate disease severity experimental autoimmune encephalomyelitis background multiple sclerosis ms progressive autoimmune disease characterized accumulation pathogenic inflammatory immune cells central nervous system cns subsequently causes focal inflammation demyelination axonal injury neuronal damage experimental autoimmune encephalomyelitis eae wellestablished murine model mimics key features ms presently dietary consumption foods rich phenols reported offer numerous health benefits including antiinflammatory activity one compound 4ethylguaiacol 4eg found various foods known attenuate inflammatory immune responses however whether 4eg exerts antiinflammatory effects modulating cns inflammatory immune responses remains unknown thus study assessed therapeutic effect 4eg eae using chronic relapsingremitting animal models investigated immunomodulatory effects 4eg neuroinflammation th1 th17 differentiation eaemethodschronic c57bl 6 eae relapsingremitting sjl j eae induced followed 4eg treatment effects 4eg disease progression peripheral th1 th17 differentiation cns th1 th17 infiltration microglia mg activation bloodbrain barrier bbb disruption eae evaluated addition expression mmp9 mmp3 ho1 nrf2 assessed cns c57bl 6 eae miceresultsour results showed 4eg ameliorated disease severity c57bl 6 chronic eae also mitigated disease progression sjl j relapsingremitting eae investigations cellular molecular mechanisms revealed 4eg suppressed mg activation mitigated bbb disruption repressed mmp3 mmp9 production inhibited th1 th17 infiltration cns eae furthermore 4eg suppressed th1 th17 differentiation periphery eae vitro th1 th17 cultures finally found 4eg induced ho1 expression cns eae vivo well mg bv2 cells macrophages vitroconclusionsour work demonstrates 4eg confers protection autoimmune disease eae modulating neuroinflammation inhibiting th1 th17 differentiation suggesting 4eg natural compound potentially developed therapeutic agent treatment ms eae,1.0
circular rna circ_0128846 promotes progression osteoarthritis regulating mir1275p nampt axis background mounting evidence indicates circular rnas circrnas participate occurrence development various diseases including osteoarthritis oa however effects molecular mechanism circ_0128846 oa reportedmethodsthe expression levels circ_0128846 microrna1275p mir1275p nicotinamide phosphoribosyltransferase nampt determined quantitative realtime polymerase chain reaction qrtpcr western blot assay cell viability determined cell counting kit8 cck8 assay cell apoptosis examined flow cytometry western blot assay inflammatory response cartilage extracellular matrix ecm degradation evaluated western blot assay relationship mir1275p circ_0128846 nampt predicted bioinformatics tools verified dualluciferase reporter rna immunoprecipitation rip assaysresultscirc_0128846 nampt upregulated mir1275p downregulated oa cartilage tissues knockdown circ_0128846 increased cell viability inhibited apoptosis inflammation ecm degradation oa chondrocytes effects reversed downregulating mir1275p moreover circ_0128846 positively regulated nampt expression sponging mir1275p furthermore mir1275p promoted cell viability suppressed apoptosis inflammation ecm degradation oa chondrocytes directly targeting namptconclusioncirc_0128846 knockdown might inhibit progression oa upregulating mir1275p downregulating nampt offering new insight potential application circ_0128846 oa treatment,0.0
explaining facilitators quality life patients multiple sclerosis qualitative study background patients multiple sclerosis ms diseases complications manifestations affect persons ability function normally leads disruptions education family life job opportunities daily life activities thereby reduce quality life different factors facilitators inhibitors affect quality life patients ms study aimed explain facilitators quality life patients msmethodsthis research applied qualitative methodology utilizing semistructured interviews individuals ms family members caregivers purposeful sampling done among people referred isfahan ms association participants selected maximum variation terms gender age education occupation marital status interviews continued reach data saturation gathered data concurrently analyzed content analysis technique maxqda software version 10 used data managementresultssaturation reached eighteen interviews total three main categories 8 subcategories extracted data identified facilitators personal facilitators leisure time coping strategies interpersonal facilitators exercise therapy social support social organizations needs suggestions improvement family therapy adopting urban architecture facilities supportive systems conclusionsbased findings order improve quality life patients ms pay attention factors leisure time spirituality positive thinking exercise social support social organizations health professionals government community families help improve patients quality life adapting urban architecture holding family therapy sessions providing supportive systems,0.0
perturbed microbiota immune homeostasis multiple sclerosis neurol neuroimmunol neuroinflamm 2021 may 11 8 4 e997 doi 101212 nxi0000000000000997 print 2021 julabstractobjective based animal models human studies now strong suspicion host microbiota mutualism context gut microbial dysbiosis influence immunity multiple sclerosis ms evolution goal seek evidence deregulated microbiotainduced systemic immune responses patients msmethods investigated gut systemic commensalspecific antibody responses healthy controls n 32 patients relapsingremitting ms n 30 individuals clinically isolated syndromes ciss n 15 gut microbiota composition diversity compared controls patients analysis 16s ribosomal ribonucleic acid rrna sequencing autologous microbiota cultivable bacterial strains used bacterial flow cytometry assays quantify autologous serum igg secretory iga responses microbiota iggbound bacteria sorted flow cytometry identified using 16s rrna sequencingresults show commensalspecific gut iga responses drastically reduced patients severe ms disease severity correlated igacoated fecal microbiota fraction r 0647 p 00001 time igaunbound bacteria elicit qualitatively broad quantitatively increased serum igg responses patients ms cis compared controls 41 25 vs 19 respectively p 0001 conclusions gut systemic microbiota immune homeostasis perturbed ms results argue defective iga responses ms linked breakdown systemic tolerance gut microbiota leading enhanced triggering systemic igg immunity gut commensals occurring early mspmid33975914 doi101212 nxi0000000000000997,0.0
overview efficacy safety ozanimod treatment relapsing multiple sclerosis drug des devel ther 2021 may 11 1519932004 doi 102147 dddts240861 ecollection 2021abstractmultiple sclerosis ms complex disease central nervous system can cause permanent disability young adults large armamentarium available management increasing time ozanimod oral drug belonging sphingosine1phosphate receptor s1pr modulator family recently approved different countries ms active disease selectively modulates s1pr1 s1pr5 prevent autoreactive lymphocytes entering central nervous system cns can determine inflammation neurodegeneration ozanimod tested one phase ii two phase iii pivotal trials shown effective well tolerated moreover investigations including comparative trials s1p modulators ms diseasemodifying drugs needed better define placement ms treatment furthermore ozanimod currently evaluation inflammatory bowel diseases ulcerative colitis crohns disease international phase iii studies article retraces itinerary leading approval ozanimod ms treatment peculiarities potentiality inside s1pr modulator familypmid34007159 pmcpmc8123972 doi102147 dddts240861,0.0
ripk1 activation mediates neuroinflammation disease progression multiple sclerosis cell rep 2021 may 11 35 6 109112 doi 101016 jcelrep2021109112abstractreceptor interacting protein kinase 1 ripk1 mediates cell death inflammatory signaling increased multiple sclerosis ms brain samples investigate role glial ripk1 kinase activity mediating ms pathogenesis demonstrate ripk1 levels correlate ms disease progression find microglia susceptible ripk1mediated cell death identify inflammatory gene signature may contribute neuroinflammatory milieu ms patients uncover distinct role ripk1 astrocytes regulating inflammatory signaling absence cell death confirm ripk1kinasedependent regulation human glia using murine ms model show ripk1 inhibition attenuates disease progression suppresses deleterious signaling astrocytes microglia results suggest ripk1 kinase activation microglia astrocytes induces detrimental neuroinflammatory program contributes neurodegenerative environment progressive mspmid33979622 doi101016 jcelrep2021109112,0.0
comprehensive cell type decomposition circulating cellfree dna celfie nat commun 2021 may 11 12 1 2717 doi 101038 s4146702122901xabstractcirculating cellfree dna cfdna bloodstream originates dying cells promising noninvasive biomarker cell death propose algorithm celfie accurately estimate relative abundances cell types tissues contributing cfdna epigenetic cfdna sequencing contrast previous work celfie accommodates low coverage data require cpg site curation estimates contributions multiple unknown cell types available external reference data simulations celfie accurately estimates known unknown cell type proportions low coverage noisy cfdna mixtures including cell types composing less 1 total mixture used two clinicallyrelevant situations celfie correctly estimates large placenta component pregnant women elevated skeletal muscle component amyotrophic lateral sclerosis als patients consistent occurrence muscle wasting typical patients together results show celfie useful tool biomarker discovery monitoring progression degenerative diseasepmid33976150 doi101038 s4146702122901x,0.0
analytical design multithreshold high fanin dnabased logical sensors profile pattern ms micrornas biomed eng lett 2021 may 11 11 2 131145 doi 101007 s13534021001869 ecollection 2021 mayabstractearly detection diseases important increase life quality reduce treatment cost patient micrornas introduced recent years efficient class biomarkers detecting risky situation many diseases cancers multiple sclerosis ms heart attacks diseases now realtime pcr used profile microrna expression expensive timeconsuming low accuracy recently dna logic gates used detect microrna expression level accurate faster previous methods paper improved design multithreshold multiinput dnabased logic gates response specific microrna mirna inputs proposed design style can simultaneously recognize multiple mirnas different rising falling thresholds proposed structure paper used diagnose multiple sclerosis ms case study simulated system understand performance compare existing methods simulation results show efficiency proposed method terms accuracy efficiency speed analysis unwanted reactions fault positive probability generating final output using formal method investigated depth finally proposed solutions improved based results analyses analytic approach paper helps design dnabased logic gates real diseasespmid34150349 pmcpmc8155178 doi101007 s13534021001869,0.0
il9triggered lncrna gm13568 regulates notch1 astrocytes interaction cbp p300 contribute pathogenesis experimental autoimmune encephalomyelitis j neuroinflammation 2021 may 11 18 1 108 doi 101186 s12974021021565abstractbackground interleukin 9 il9 produced mainly t helper 9 th9 cells recognized important regulator multiple sclerosis ms animal model experimental autoimmune encephalomyelitis eae astrocytes respond il9 reactive astrocytes always associate bloodbrain barrier damage immune cell infiltration spinal injury ms eae several long noncoding rnas lncrnas aberrant expression identified pathogenesis ms examined effects lncrna gm13568 coupregulated lncrna eae mice mouse primary astrocytes activated il9 activation astrocytes process eaemethods vitro shrnarecombinant lentivirus glial fibrillary acidic protein gfap promoter performed determine relative gene expression proinflammatory cytokines production il9 treatedastrocytes using western blot realtime pcr cytometric bead array respectively rip chip assays analyzed mechanism lncrna gm13568 regulating gene expression immunofluorescence assays performed measure protein expression astrocytes vivo staining lfb staining applied detect inflammatory cells infiltrations medullary sheath damage spinal cords eae mice infected recombinant lentivirus results analyzed oneway anova students t test appropriateresults knockdown endogenous lncrna gm13568 remarkably inhibits notch1 expression astrocytosis phosphorylation signal transducer activator transcription 3 pstat3 well production inflammatory cytokines chemokines il6 tnf ip10 il9activated astrocytes gm13568 associates transcriptional coactivators cbp p300 enriched promoter notch1 genes importantly inhibiting gm13568 lentiviral vector astrocytes ameliorates significantly inflammation demyelination eae mice therefore delaying eae processconclusions findings uncover gm13568 regulates production inflammatory cytokines active astrocytes affects pathogenesis eae notch1 stat3 pathway lncrna gm13568 may promising target treating ms demyelinating diseasespmid33971906 doi101186 s12974021021565,1.0
temporal summation mechanical pain prospectively predicts movementevoked pain severity adults chronic low back pain background biopsychosocial factors beyond pathoanatomical changes likely contribute severity chronic low back pain pronociceptive endogenous pain modulatory balance inhibition facilitation may important contributor chronic low back pain severity physical function however additional research needed address possibility objective study determine whether quantitative sensory tests endogenous pain inhibition facilitation prospectively predict movementevoked pain clbp severity selfreported validated questionnairemethodsone hundred thirtyfour individuals chronic low back pain enrolled twosession study first study session temporal summation mechanical pain conditioned pain modulation assessed lumbar spine determine endogenous pain facilitation inhibition respectively one week later participants returned second study session whereby reported pain severity pain interference using brief pain inventoryshort form movementevoked pain physical function capacity assessed upon completion balance walking transition sit stand tests short physical performance batteryresultstemporal summation mechanical pain conditioned pain modulation significantly prospectively predicted greater movementevoked pain poorer physical function short physical performance battery neither temporal summation conditioned pain modulation significantly related selfreported pain severity pain interference brief pain inventoryshort formconclusionsfindings suggest pronociceptive pain modulatory balance characterized enhanced pain facilitation may important driver movementevoked pain severity poor physical function individuals chronic low back pain,0.0
accuracy hospital anxiety depression scale depression subscale hadsd screen major depression systematic review individual participant data metaanalysis bmj 2021 may 10 373n972 doi 101136 bmjn972abstractobjective evaluate accuracy depression subscale hospital anxiety depression scale hadsd screen major depression among people physical health problemsdesign systematic review individual participant data metaanalysisdata sources medline medline inprocess nonindexed citations psycinfo web science inception 25 october 2018 review methods eligible datasets included hadsd scores major depression status based validated diagnostic interview primary study data study level data extracted primary reports combined hadsd cutoff thresholds 515 bivariate random effects metaanalysis used estimate pooled sensitivity specificity separately studies used semistructured diagnostic interviews eg structured clinical interview diagnostic statistical manual mental disorders fully structured interviews eg composite international diagnostic interview mini international neuropsychiatric interview one stage metaregression used examine whether accuracy associated reference standard categories characteristics participants sensitivity analyses done assess whether including published results studies provide raw data influenced resultsresults individual participant data obtained 101 168 eligible studies 60 25 574 participants 72 eligible participants 2549 major depression combined sensitivity specificity maximised cutoff value seven higher semistructured interviews fully structured interviews mini international neuropsychiatric interview among studies semistructured interview 57 studies 10 664 participants 1048 major depression sensitivity specificity 082 95 confidence interval 076 087 078 074 081 cutoff value seven higher 074 068 079 084 081 087 cutoff value eight higher 044 038 051 095 093 096 cutoff value 11 higher accuracy similar across reference standards subgroups published results studies contribute data includedconclusions screening major depression hadsd cutoff value seven higher maximised combined sensitivity specificity cutoff value eight higher generated similar combined sensitivity specificity less sensitive specific identify medically ill patients depression hadsd lower cutoff values used avoid false negatives higher cutoff values reduce false positives identify people higher symptom levelstrial registration prospero crd42015016761pmid33972268 doi101136 bmjn972,0.0
endogenous retroviruses origins treatment cancer abstractendogenous retroviruses ervs emerging promising therapeutic targets cancer remnants ancient retroviral infections ervderived regulatory elements coordinate expression gene networks including underpinning embryogenesis immune cell function erv activation can promote interferon response phenomenon termed viral mimicry although erv expression associated cancer provisionally autoimmune neurodegenerative diseases ervmediated inflammation explored way sensitize tumors immunotherapy review erv cooption development innate immunity aberrant contribution ervs tumorigenesis wider biomedical potential therapies directed ervs,0.0
effects menstrual cycle neurological disorders curr neurol neurosci rep 2021 may 10 21 7 34 doi 101007 s11910021011150abstractpurpose review menstrual cycle involves recurrent fluctuations hormone levels temperature via neuroendocrine feedback loops paper reviews impact menstrual cycle several common neurological conditions including migraine seizures multiple sclerosis stroke parkinsons diseaserecent findings ovarian steroid hormones estrogen progesterone protean effects central nervous system functioning can impact likelihood severity presentation many neurological diseases hormonal therapies explored potential treatment many neurological diseases varying degrees evidence success neurological conditions also impact womens reproductive health cessation ovarian function menopause may also alter course neurological diseases medication selection must consider hormonal effects metabolism potential adverse drug reactions related menstruation fertility pregnancy outcomes novel medications selective affinity hormonal receptors desirable neurologists gynecologists must collaborate provide optimal care women neurological disorderspmid33970361 doi101007 s11910021011150,0.0
treatment progressive multiple sclerosis highdose alltrans retinoic acid clear evidence positive disease modifying effects background alltrans retinoic acid atra acid derivative vitamin discussed promising candidate ameliorate disease course multiple sclerosis ms immunomodulation even promoting regeneration progressive ms report patient significantly improved ms related disability following administration chemotherapy including atra mitoxantronerelated acute promyelocytic leukemia assess effect highdose atra three additional patients progressive msmethodspatients progressive ms failed previous therapies treated highdose atra patients underwent clinical routine laboratory monitoring additionally pbmcs analyzed flow cytometry lymphocyte subsetsresultsatra well tolerated pathological laboratory abnormalities observed initial mild statistically significant improvement edss mean msfc zscore ongoing disease progression observed one patient subacutely experienced severe cognitive motor worsening cerebral mri revealed persistent gadoliniumenhancing lesions flow cytometric alterations peripheral blood nave central memory effector memory cd4 cd8 t cells b lymphocytes plasma cells memory b cells plasmablasts natural killer nk cells reach statistical significanceconclusionsstandalone therapy atra ameliorate progressive ms limited cohort observe consistent alterations t b cell subsets intriguingly application atra may caused marked disease exacerbation one patient,0.0
diseasemodifying therapy multiple sclerosis tidsskr laegeforen 2021 may 10 141 8 doi 104045 tidsskr210155 print 2021 may 25no abstractpmid34047171 doi104045 tidsskr210155,0.0
dhodh cancer promising prospects explored abstracthuman dihydroorotate dehydrogenase dhodh flavindependent mitochondrial enzyme catalyzing fourth step de novo pyrimidine synthesis pathway originally target treatment nonneoplastic diseases involving rheumatoid arthritis multiple sclerosis reemerging validated therapeutic target cancer therapy review mainly unravel biological function dhodh tumor progression including crucial role de novo pyrimidine synthesis mitochondrial respiratory chain cancer cells moreover various dhodh inhibitors developing past decades also displayed specific mechanism dhodh additional effects illustrated collectively detailly discuss association dhodh tumors recent years believe will provide significant evidences potential strategies utilizing dhodh potential target preclinical clinical cancer therapies,0.0
cardiovascular magnetic resonance women cardiovascular disease position statement society cardiovascular magnetic resonance scmr abstractthis document position statement society cardiovascular magnetic resonance scmr recommendations clinical utilization cardiovascular magnetic resonance cmr women cardiovascular disease document prepared scmr consensus group cmr imaging female patients cardiovascular disease endorsed scmr publications committee scmr executive committee goals document 1 guide informed selection cardiovascular imaging methods 2 inform clinical decisionmaking 3 educate stakeholders advantages cmr specific clinical scenarios 4 empower patients clinical evidence participate clinical care statements clinical utility presented current document pertain following clinical scenarios acute coronary syndrome stable ischemic heart disease peripartum cardiomyopathy cancer therapyrelated cardiac dysfunction aortic syndrome congenital heart disease pregnancy bicuspid aortic valve aortopathies systemic rheumatic diseases collagen vascular disorders cardiomyopathycausing mutations authors cite published evidence available provide expert consensus otherwise evidence available pertains translational studies involving subjects sexes however authors prioritized review data obtained female patients direct comparison cmr women men position statement consider cmr accessibility availability local expertise instead highlights optimal utilization cmr women known suspected cardiovascular disease finally ultimate goal position statement improve health female patients cardiovascular disease providing specific recommendations use cmr,0.0
oral manifestations patients systemic sclerosis metaanalysis casecontrolled studies background systemic sclerosis ssc multisystem rheumatic disease orofacial manifestations commonly ssc maybe usually ignored overshadowed systemic complications multiple comparative studies conducted investigate possible links ssc oral manifestations present study aimed investigate oral health status patients ssc methodspubmed embase web science scopus searched july 2020 following outcomes evaluated probing depth pd attachment loss al bleeding probing bop number percentage sites pd 4 mm prevalence periodontitis number teeth decayed teeth missing teeth filled teeth dmft index interincisal distance newcastleottawa scale nos applied quality assessment statistical analysis processed using software stataresults11 eligible studies included maximum interincisor distance significantly restricted ssc patients smd 1061 95 ci 1546 0576 z 429 p 0000 prevalence periodontitis 7007 95 ci 3529 13915 z 556 p 0000 pd smd 3101 95 ci 1374 4829 z 352 p 0000 al smd 2584 95 ci 0321 4846 z 224 p 0025 sites pd 4mm smd 2071 95 ci 0267 3875 z 225 p 0024 number decayed teeth smd 0186 95 ci 0007 0365 z 204 p 0041 increased significantly ssc population comparison controlsconclusionsssc patients limited mouth opening higher periodontitis prevalence worse periodontal status well increased number decayed teeth routinely oral hygiene instruction initial periodontal treatment recommended ssc patients,0.0
correction clinical feasibility umbilical cord tissuederived mesenchymal stem cells treatment multiple sclerosis amendment paper published can accessed via original article,0.0
radiologic findings aid reduction misdiagnoses langerhans cell histiocytosis bone retrospective study background study aimed identify characteristic radiological signs diagnosis langerhans cell histiocytosis lch bonemethodswe retrospectively studied 82 cases lch bone lesions confirmed pathology clinical radiological features patients analyzedresultsa total 64 18 patients single multiple bone lesions respectively regard lch single bone lesions 375 24 64 lesions located skull presented bone destruction without soft tissue mass correct diagnosis rate lesions 600 9 15 children adolescents 222 2 9 adultsa total 265 17 64 solitary lesions found spine 882 15 17 located vertebral body appeared different degrees collapse 667 10 15 lesions correctly diagnosedof unifocal lesions 218 14 64 located flat irregular bones manifested osteolysis 214 3 14 cases correctly diagnosedin total 141 9 64 isolated bone lch lesions located long bones 778 7 9 located diaphysis presented central bone destruction without fusiform periosteal reaction extensive peripheral edema 429 3 7 correctly diagnosed surgery biopsywith regard lch multiple bony destructive lesions 714 10 14 cases children adolescents correctly diagnosed however four cases among adults misdiagnosedconclusionin age groups isolated diaphyseal destruction long bone fusiform periosteal reaction extensive peripheral edema vertebra plana spine bevelled edge skull defects accompanied soft tissue masses strongly suggest lch diagnosis moreover multiple bone osteolytic destruction children adolescents strongly suggests lch diagnosis familiarity typical radiological signs lch necessary decrease misdiagnoses,0.0
genetic screening prenatal diagnosis highrisk families tuberous sclerosis complex syndrome zhonghua yi xue yi chuan xue za zhi 2021 may 10 38 5 435438 doi 103760 cmajcn5113742020032500203abstractobjective carry genetic testing prenatal diagnosis 29 chinese pedigrees affected tuberous sclerosis complex tsc assess efficacy combined next generation sequencing ngs multiple ligationdependent probe amplification mlpa diagnosismethods ngs mlpa used conjunct detect variants tsc1 tsc2 genes among probands pedigrees paternity test carried exclude maternal dna contamination prenatal diagnosis provided 14 couples based discoveries probandsresults twentyseven variants identified tsc1 tsc2 genes among 29 pedigrees yielded detection rate 931 respectively 5 185 22 815 variants identified tsc1 tsc2 genes twelve variants unreported previously prenatal diagnosis showed five fetuses affected tsc whilst remaining nine unaffectedconclusion finding expanded spectrum tsc1 tsc2 gene variants combined ngs mlpa enabled diagnosis tsc efficiency accuracypmid33974250 doi103760 cmajcn5113742020032500203,0.0
standardized endoscopic swallowing evaluation tracheostomy decannulation critically ill neurologic patients prospective evaluation background removal tracheostomy tube critically ill neurologic patients critical issue intensive care treatment particularly due severe dysphagia insufficient airway protection standardized endoscopic evaluation tracheostomy decannulation critically ill neurologic patients sesetd objective measure readiness decannulation protocol includes stepwise evaluation secretion management spontaneous swallowing laryngeal sensitivity fiberoptic endoscopic evaluation swallowing fees first evaluated safety secondly effectiveness protocol sought identify predictors decannulation success decannulation failuremethodsa prospective observational study conducted neurological intensive care unit mnster university hospital germany january 2013 december 2017 three hundred seventyseven tracheostomized patients acute neurologic disease completely weaned mechanical ventilation included examined fees within 72 h end mechanical ventilation using regression analysis predictors successful decannulation well decannulation failure investigatedresultstwo hundred twentyseven patients 602 decannulated stay according protocol 59 within 24 h initial fees completed weaning 35 patients recannulated due severe dysphagia related complications prolonged mechanical ventilation showed significant predictor decannulation failure lower age identified significant predictor early decannulation end weaning transforming binary sesetd 4point scale helped predicting decannulation success patients immediately ready decannulation end respiratory weaning optimal cutoff 1 sensitivity 64 specifity 66 conclusionsthe sesetd showed safe efficient tool evaluate readiness decannulation patient collective critically ill neurologic patients,0.0
notching knowledge molecular mechanisms skin fibrosis focus multifaceted notch signalling pathway abstractfibrosis can defined excessive deregulated deposition extracellular matrix proteins causing loss physiological architecture dysfunction different tissues organs skin fibrosis represents hallmark several acquired eg systemic sclerosis hypertrophic scars inherited ie dystrophic epidermolysis bullosa diseases complex series interactions among variety cellular types wide range molecular players drive fibrogenic process often contextdependent manner however pathogenetic mechanisms leading skin fibrosis completely elucidated scenario increasing body evidence recently disclosed involvement notch signalling cascade fibrosis skin organs despite apparent simplicity notch represents one multifaceted strictly regulated intricate pathways still unknown features health disease conditions starting recent advances notch activation regulation review focuses profibrotic function notch pathway fibroproliferative skin disorders describing molecular networks interplay profibrotic molecules pathways including transforming growth factor1 therapeutic strategies development,0.0
window future mri evaluation neuromyelitis optica spectrum disorder throughout disease course ther adv neurol disord 2021 may 9 1417562864211014389 doi 101177 17562864211014389 ecollection 2021abstractneuromyelitis optica spectrum disorder nmosd relapsing inflammatory disease central nervous system marked relapses often associated poor recovery longterm disability magnetic resonance imaging mri recognized important tool timely diagnosis nmosd combination serologic testing aids distinguishing nmosd possible mimics although role mri disease monitoring diagnosis well established mri may provide important prognostic information help differentiate relapses pseudorelapses increasing evidence subclinical disease activity emergence newly approved highly effective immunotherapies nmosd adjure us reevaluate mri tool guide optimal treatment selection escalation throughout disease course article review role mri nmosd diagnosis prognostication disease monitoring treatment selectionpmid34035837 pmcpmc8111516 doi101177 17562864211014389,0.0
hazai sclerosis multiplex betegpopulacio eletkori es nemi megoszlasa 2004 es 2016 kozott orv hetil 2021 may 9 162 19 746753 doi 101556 650202132100abstractsszefoglal bevezets mivel haznkban sclerosis multiplex gyakorisgrl valamint letkori s nemi jellegzetessgeirl az elmlt vtizedekben egszen 2020ig csak regionlis jelleg felmrsek kszltek egyegy centrum betegforgalma alapjn az jonnan diagnosztizlt s mr ismert betegek orszgos koreloszlsrl s annak idbeli vltozsairl nincsenek ismereteink clkitzs jelen munknkban tbb mint 14 000 beteg adatainak elemzsvel prevalens s incidens betegek koreloszlsnak vltozst vizsgljuk 20042016 sorn s eredmnyeinket sszevetjk az elmlt vtizedekben kzlt hazai adatokkal mdszer munkacsoportunk az egszsgbiztostsi pnztr anonimizlt neurohun adatbzist elemezte amely tartalmazza 2004 s 2016 kztt az sszes hazai llamilag finanszrozott fekv s jrbetegszakelltsbl neurolgiai diagnzissal jelentett esetet sclerosis multiplex bnokdjnak elfordulsa alapjn korbban ltrehoztuk betegsg adminisztratv defincijt s megbecsltk sclerosis multiplex orszgos prevalencijt s incidencijt eredmnyek prevalens betegek tlagletkora 2015ben 47 9 v ugyanebben az vben az incidens betegek tlagletkora 37 4 v volt vizsglatunk szerint prevalens betegek tlagletkora szignifiknsan vente egytdegyharmad vvel p0 001 emelkedik mgpedig nk esetben nagyobb mrtkben nk tlagosan fl vvel idsebbek mint frfi pciensek szignifikns klnbsg p 0 002 prevalens betegekben legnpesebb korosztly az tvenvesek fell fiatalabb 3540 ves korosztly fel mozdul az incidens betegek tlagletkora lassan de szignifiknsan vente tlagosan egyharmad vvel p0 001 cskken kvetkeztets eredmnyeink szerint az jonnan diagnosztizlt sclerosis multiplexes pciensek tlagosan egyre fiatalabbak s prevalens betegek kztt egyre fiatalabb korosztlyok legnpesebbek de javul tlls s hosszabb lettartam miatt prevalens betegek tlagletkora sszessgben valsznleg fokozatosan emelkedik orv hetil 2021 162 19 746753introduction nationwide age gender distribution newly diagnosed prevalent multiple sclerosis patients unknown hungary 2020 regional studies reported frequency age characteristics subjects multiple sclerosis based singlecenter patient registriesobjective present study analysis 14 000 patients describe changes age distribution prevalent incident subjects 2004 2016 compare results data published subject last decades hungarymethod analyzed pseudonymized neurohun database provided singlepayer national health insurance fund contains claim submitted public hospitals outpatient services neurologic diseases 2004 2016 using icd10code multiple sclerosis previously established administrative definition illness estimated prevalence incidence countryresults mean age prevalent patients 479 years 2015 whereas year mean age incident cases 374 years average age prevalent patients shows significant rise annual increase one fifthone third year p0001 pronounced increase among women age women higher half year p 0002 populous age groups among prevalent subjects shift fifties towards younger generations 3540 years age average age incident subjects slowly significantly decreases mean annual decrease one third year p0001 conclusion results suggest though new patients younger yearbyyear populous age groups also younger altogether average age prevalent subjects continuously increases probably due longer survival lifespan patients multiple sclerosis orv hetil 2021 162 19 746753pmid33965907 doi101556 650202132100,0.0
fli1 deficiency suppresses raldh1 activity dermal dendritic cells related induction regulatory t cells possible role scleroderma background aldehyde dehydrogenase 1 family member a1 raldh1 producing dermal dendritic cells dcs conventional dc subset regulating skin fibrosis decreased involved skin patients systemic sclerosis ssc study investigated contribution fli1 deficiency potential predisposing factor ssc phenotypical alteration raldh1producing dermal dcs using ssc model mice ssc skin samplesmethodsbleomycin blm induced skin fibrosis generated fli1+ wildtype mice proportions dc cd4+ t cell subsets determined flow cytometry dermis blmtreated mice fli1 expression dermal dcs evaluated immunofluorescence skin samples ssc healthy control subjectsresultsraldh activity dermal dcs significantly decreased blmtreated fli1+ mice compared blmtreated wildtype mice whereas proportion cd103cd11b dermal dcs major dc subset producing raldh1 response blm injection comparable groups relevant finding proportion regulatory t cells tregs dermis decreased blmtreated fli1+ mice relative blmtreated wildtype mice proportions th1 th2 th17 cells unaltered involved skin ssc patients fli1 downregulated cd11c+ cells including dermal dcsconclusionsfli1 deficiency inhibits raldh1 activity cd103cd11b dermal dcs related induction tregs blmtreated mice considering fli1 reduction ssc dermal dcs fli1deficiency may impair dermal dctreg system contributing development skin fibrosis ssc,0.0
early onset senescence cognitive impairment murine model repeated mtbi abstractmild traumatic brain injury mtbi results broad neurological symptoms increased risk diagnosed neurodegenerative disease later life immediate oxidative stress response postmortem pathology injured brain well studied remains unclear early pathogenic changes may drive persistent symptoms confer susceptibility neurodegeneration study used mouse model repeated mtbi rmtbi identify early gene expression changes 24 h 7 days postinjury 7 dpi 24 h postinjury gene expression rmtbi mice shows activation dna damage response ddr towards double strand dna breaks altered calcium cellcell signalling inhibition cell death pathways 7 dpi rmtbi mice gene expression signature consistent induction cellular senescence activation neurodegenerative processes inhibition ddr timepoints gliosis microgliosis axonal damage evident absence gross lesion 7 dpi rmtbi also mice elevated levels il1 p21 53bp1 dna2 p53 supportive dna damageinduced cellular senescence gene expression changes reflect establishment processes usually linked brain aging suggests cellular senescence occurs early likely prior accumulation toxic proteins molecular changes accompanied spatial learning memory deficits morris water maze conclude identified dna damageinduced cellular senescence repercussion repeated mild traumatic brain injury correlates cognitive impairment pathways involved senescence may represent viable treatment targets postconcussive syndrome senescence proposed promote neurodegeneration appears effective target prevent longterm complications mtbi chronic traumatic encephalopathy related neurodegenerative pathologies,0.0
subgingival microbiome deep shallow periodontal sitesin patients rheumatoid arthritis pilot study background subgingival microbiome diseaseassociated subgingival sites known dysbiotic significantly altered patients rheumatoid arthritis ra extent dysbiosis disease healthassociated subgingival sites clearmethods8 ra 10 nonra subjects recruited pilot study subjects received full oral examination underwent collection subgingival plaque samples shallow periodontal healthassociated probing depth 3mm deep subgingival sites periodontal diseaseassociated probing depth 4 mm ra subjects also rheumatological evaluation plaque community profiles analyzed using 16 s rrna sequencingresultsthe phylogenetic diversity microbial communities ra nonra controls significantly higher deep subgingival sites compared shallow sites p 0022 overall subgingival microbiome clustered primarily according probing depth ie shallow versus deep sites separated ra status large number differentially abundant taxa gene functions observed deep shallow sites expected nonra controls found differentially abundant taxa gene functions deep shallow sites ra subjects addition compared nonra controls unifrac distances deep shallow sites ra subjects smaller suggesting increased similarity deep shallow subgingival microbiome ra streptococcus parasanguinis actinomyces meyeri overabundant ra subjects gemella morbillorum kingella denitrificans prevotella melaninogenica leptotrichia spp abundant nonra subjectsconclusionsthe aggregate subgingival microbiome significantly different individuals without rheumatoid arthritis although differences overall subgingival microbiome driven primarily probing depth contrast substantial microbiome differences typically seen deep shallow sites nonra patients microbiome deep shallow sites ra patients similar results suggest factors associated ra may modulate ecology subgingival microbiome relationship periodontal disease basis remains unknown warrants investigation,0.0
epiphyseal enchondroma masking osteoid osteoma case report background enchondromas originating epiphyses long bones rare epiphyseal osteoid osteomas also uncommon diagnosis can become elusive enchondromas osteoid osteomas occur atypical locations present nonspecific clinical imaging characteristicscase presentationwe report case epiphyseal enchondroma left proximal femur 15yearold girl 2month history left lower extremity pain preoperative ct displayed thickened cortex anterior surface left proximal femur specks calcification inhomogeneity adjacent bone marrow cavity diagnosed osteoid osteoma postoperative pathological examination surgically excised specimens revealed diagnosis enchondromasconclusionsour case highlights enchondroma considered lesions epiphysis,0.0
repeated infusion mesenchymal stem cells maintain condition inhibit deteriorated motor function leading extended lifespan sod1g93a rat model amyotrophic lateral sclerosis abstractamyotrophic lateral sclerosis als neurodegenerative fatal disorder motor neurons within brain spinal cord degenerate single infusion mesenchymal stem cells mscs delays disease progression protecting motor neurons restoring bloodspinal cord barrier sod1g93a transgenic als rat model however therapeutic effect single infusion mscs transient block disease progression study demonstrated repeated administration mscs weekly four times increased survival period protected motor functions reduced deterioration locomotor activity compared single infusion vehicle infusion rats displayed progressive deterioration hind limb function also compared days gait ability lost rats found repeatedinfused group maintained gait ability compared singleinfusion vehicleinfusion groups results suggest repeated administration mscs may prevent deterioration motor function extend lifespan als,0.0
smartphone app hamster tracking patientreported outcomes people multiple sclerosis protocol pilot study jmir res protoc 2021 may 7 10 5 e25011 doi 102196 25011abstractbackground treatment monitoring decisions people multiple sclerosis ms based commonly clinicianreported outcomes reflect physical radiological disease activity relevant endpoints clinical trials past years number studies evaluating socalled patientreported outcomes pros increasing pros reports patients concerning health perception typically obtained means questionnaires aim quantify symptoms fatigue depression sexual dysfunction emergence pros made tremendous contribution understanding individual impact disease people ms healthrelated quality life however assessment pros consumes resources including time personnel thus useful ways conveniently introduce pros clinical practice neededobjective aim provide rationale pilot study protocol mobile health mhealth solution named hamster allows remote monitoring pros people msmethods core function hamster provide three scientifically validated pro questionnaires relevant ms patients fill home month thereby longitudinal remote documentation pros enabled scoring algorithm graphically plots pro scores time makes available next visitresults pilot study currently ongoing will evaluate adherence mhealth solution 50 patients period 6 months results hamster pilot study expected 2021conclusions hamster novel mhealthbased solution modern pro research may constitute first step achieving ability integrate pros clinical practice allows problemoriented approach monitoring visits addresses patient needs ultimately saves timetrial registration clinicaltrialsgov nct04555863 https clinicaltrialsgov ct2 show nct04555863international registered report identifier irrid derr1102196 25011pmid33960949 doi102196 25011,0.0
neurological pathogenesis sarscov2 covid19 virological features clinical symptoms abstractsince worldwide outbreak coronavirus disease 2019 covid19 2020 various research reports case reports published found covid19 causes respiratory disorders also thrombosis gastrointestinal disorders central nervous system cns disorders peripheral neuropathy compared disorders low number research reports low number summaries covid19related neural disorders therefore focusing neural disorders outline basic research clinical manifestations covid19related neural disorders,0.0
hypotony maculopathy photoreceptor folds disruptions vitrectomy epiretinal membrane removal two case reports background hypotony maculopathy classically reported complication glaucoma surgery ocular trauma reports hypotony maculopathy following pars plana vitrectomy ppv report two cases hypotony maculopathy occurring ppv epiretinal membrane erm removal characteristic photoreceptor folds observed optical coherence tomography oct case presentationa 53yearold korean woman case 1 underwent phacoemulsification posterior chamber lens implantation combined 25gauge ppv erm removal right eye following day severe ocular hypotony intraocular pressure iop unmeasurable using pneumatic tonometer despite normalization iop macular retinal photoreceptor folds photoreceptor disruptions developed henles fiber layer hyperreflectivity identified thereafter retinal photoreceptor folds gradually disappeared photoreceptor disruption henles fiber layer hyperreflectivity improve 1 year postoperatively persistent central visual field distortion visual acuity worse preoperative state 20yearold korean man case 2 underwent additional 25gauge ppv erm removal left eye examination following day showed ocular hypotony retinal folds peripheral choroidal detachment although iop normalized oct revealed photoreceptor folds photoreceptor disruptions since photoreceptor folds resolved however photoreceptor disruption remained macula 1year follow persistent distorted vision visual acuity worse preoperative stateconclusionsearly hypotony vitrectomy erm result maculopathy leading irreversible visual decline metamorphopsia photoreceptor folds oct characteristic features predominant mechanism central visual loss cases hypotony maculopathy,0.0
innovative medical technology treatment decisionmaking process multiple sclerosis focus group study examine patient perspectives patient prefer adherence 2021 may 7 15927937 doi 102147 ppas306132 ecollection 2021abstractbackground diseasemodifying therapies given people multiple sclerosis ms reduce disease progression relapse frequency current modes administration include oral injectable infusion therapy treatment decisionmaking process complex novel mode treatment administration implantable device currently development yet patient attitudes device unknown aim study 1 understand treatment decisionmaking process patient perspective 2 explore possible acceptance implant treat msmethods focus groups people ms conducted netherlands three topics addressed treatment decisionmaking process current treatment landscape attitudes implantable device focus groups recorded transcribed data analyzed raw data coding creating themes online survey conducted netherlands quantify interest implantresults two focus group sessions held n16 participants n93 persons filled survey main theme emerged constant uncertainty persons ms face throughout disease course treatment decisions start stop continue switch treatment patients generally positive towards implant felt efficacy safety guaranteedconclusion people ms want form control disease treatment course new medical technologies implant may enhance treatment landscape caution postulate may accepted patients new mode administration though research needed medical technologies successful patients engaged early design processpmid33994779 pmcpmc8114356 doi102147 ppas306132,0.0
neurofilament light narrative review biomarker utility fac rev 2021 may 7 1046 doi 1012703 r 1046 ecollection 2021abstractneurofilament light nfl scaffolding protein located primarily within myelinated axons provides increased conduction speed structural support recent years nfl used disease biomarker basis observation axonal injury results elevated levels nfl cerebrospinal fluid blood review focuses cerebrospinal fluid plasma nfl studied various disorders alzheimers disease ad multiple sclerosis ms relation neuroinflammation cognitive dysfunction focusing role nfl biomarker ad ms review aims explore potential nfl promising biomarker regard surgery anesthesiabased incidents postoperative cognitive decline delirium search pubmed database yielded 36 articles 31 within last 3 years show nfl observed studied various types trials disease cohorts potential future directions higher levels nfl frequently correlated disease progression prognosis ad ms delirium found share neuroinflammatory pathophysiology nfl help measure focusing nfl biomarker neurodegenerative decline studies indicate protein tested related postoperative aspects result cognitive dysfunction potential established delirium biomarker particularly realm perioperative coursepmid34131656 pmcpmc8170685 doi1012703 r 1046,1.0
dietary conjugated linoleic acid links reduced intestinal inflammation amelioration cns autoimmunity brain 2021 apr 26awab040 doi 101093 brain awab040 online ahead printabstracta close interaction gut immune responses distant organspecific autoimmunity including cns multiple sclerosis established recent years socalled gutcns axis can shaped dietary factors either directly via indirect modulation gut microbiome metabolites report dietary supplementation conjugated linoleic acid mixture linoleic acid isomers ameliorates cns autoimmunity spontaneous mouse model multiple sclerosis accompanied attenuation intestinal barrier dysfunction inflammation well increase intestinal myeloidderived suppressorlike cells protective effects dietary supplementation conjugated linoleic acid abrogated upon microbiota eradication indicating microbiome dispensable conjugated linoleic acidmediated effects instead observed range direct antiinflammatory effects conjugated linoleic acid murine myeloid cells including enhanced il10 production capacity suppress tcell proliferation finally human pilot study patients multiple sclerosis n 15 firstline diseasemodifying treatment dietary conjugated linoleic acidsupplementation 6 months significantly enhanced antiinflammatory profiles well functional signatures circulating myeloid cells together results identify conjugated linoleic acid potent modulator gutcns axis targeting myeloid cells intestine turn control encephalitogenic tcell responsespmid33899089 doi101093 brain awab040,0.0
advanced analysis diffusion tensor imaging along machine learning provides new sensitive measures tissue pathology intralesion activity multiple sclerosis front neurosci 2021 may 7 15634063 doi 103389 fnins2021634063 ecollection 2021abstracttissue pathology multiple sclerosis ms highly complex requiring multidimensional analysis study goal test feasibility obtaining high angular resolution diffusion imaging hardi metrics singleshell modeling diffusion tensor imaging dti data investigate advanced measures singleshell hardi dti tractography perform relative classical dti metrics assessing ms pathology examined 52 relapsingremitting ms patients 3t anatomical brain mri dti singleshell hardi modeling yielded 5 subvoxelbased metrics totalling 11 diffusion measures including 4 dti 2 tractography metrics based machine learning 3dimensional regions interest evaluated importance measures several tissue classification tasks included two withinsubject comparisons lesion versus normal appearing white matter nawm lesion core versus shell stratifying patients high 75 ile low 25 ile number ms lesions also performed 2 classifications subjects lesions nawm respectively results showed lesionnawm analysis hardi orientation distribution function odf energy dti fractional anisotropy fa hardi orientation dispersion index top three metrics together achieved 652 accuracy 071 area receiver operating characteristic curve auroc coreshell analysis dti mean diffusivity md radial diffusivity fa top three metrics md dominated classification achieved 593 accuracy 059 auroc alone patients fa leading feature lesion comparisons odf energy best nawm separation collectively singleshell modeling common diffusion data can provide robust orientation measures lesion nawm pathology dti metrics sensitive intralesion abnormality combined analysis advanced classical diffusion measures may critical improved understanding ms pathologypmid34025338 pmcpmc8138061 doi103389 fnins2021634063,0.0
detection mogigg clinical samples live cellbased assays performance immunofluorescence microscopy flow cytometry front immunol 2021 may 7 12642272 doi 103389 fimmu2021642272 ecollection 2021abstracthuman antibodies myelin oligodendrocyte glycoprotein mog immunoglobuling subclasses mogigg recently associated new subgroup neurological autoimmune diseases distinct clinical characteristics multiple sclerosis neuromyelitis optica spectrum disorders use mogigg biomarker essential tool assist diagnosis clinical prognosis cellbased assay cba methodology expresses high levels natively folded human mog protein cell membrane methodology used clinical mogigg diagnosis however still consensus best approach perform cba improve results cba using flow cytometry cbafc automated technique objective quantification reducing subject human bias occurred cba using immunofluorescence cbaif study compared performance cbaif cbafc acquisition tool analysis sera 104 patients diagnosed inflammatory central nervous system diseases tested cbaif cbafc used dilution 1128 cbaif three different dilutions 120 1100 1640 cbafc cbafc cbaif results 885 agreement assays cbaif titers endpointdilution correlated cbafc titers highest serum dilution resulted increased cbafc specificity reduction cbafc sensitivity study showed cbafc can used clinical practice diagnostic technique mogigg addition specific cases combination techniques used tool discriminate unspecific binding overcome single assay limitationspmid34025652 pmcpmc8137838 doi103389 fimmu2021642272,1.0
antiinflammatory effects dimethyl fumarate microglia via autophagy dependent pathway front pharmacol 2021 may 7 12612981 doi 103389 fphar2021612981 ecollection 2021abstractdimethyl fumarate dmf approved food drug administration treatment relapsingremitting multiple sclerosis considered exert antiinflammatory antioxidant effects microglia maintain homeostasis central nervous system play key role neuroinflammation autophagy controls numerous fundamental biological processes including pathogen removal cytokine production clearance toxic aggregates however role dmf autophagy induction relationship effect antiinflammatory functions microglia well known present study investigated whether dmf inhibited neuroinflammation induced autophagy microglia first confirmed antineuroinflammatory effect dmf mice streptozotocininduced diabetic neuropathy next used vitro models including microglial cell lines primary microglial cells examine antiinflammatory neuroprotective effects dmf found dmf significantly inhibited nitric oxide proinflammatory cytokine production lipopolysaccharidestimulated microglia induced switch microglia m2 state addition dmf treatment increased expression levels autophagy markers including microtubuleassociated protein light chain 3 lc3 autophagyrelated protein 7 atg7 formation lc3 puncta microglia antiinflammatory effect dmf microglia significantly reduced pretreatment autophagy inhibitors data suggest dmf leads induction autophagy microglia antiinflammatory effects partially mediated autophagydependent pathwaypmid34025399 pmcpmc8137969 doi103389 fphar2021612981,1.0
map johnes disease microbiome current knowledge future considerations abstractmycobacterium avium subsp paratuberculosis causative agent johnes disease ruminants infectious disease causes reduced milk yields effects fertility eventually loss animal huge financial burden associated industries efforts control map infection johnes disease complicated due difficulties diagnosis early stages infection challenges relating specificity sensitivity current testing methods methods available contribute widely used test cull strategies vaccination programmes also place countries next generation sequencing technologies opened new avenues discovery novel biomarkers disease prediction within map genomes within ruminant microbiomes controlling johnes disease herds can lead improved animal health welfare turn leading increased productivity current climate change bills european green deal targeting livestock production systems sustainable practices managing animal health now important ever review provides overview current knowledge genomics detection map pertains johnes disease,0.0
design evaluation usercentered exergames patients multiple sclerosis multilevel usability feasibility studies jmir serious games 2021 may 7 9 2 e22826 doi 102196 22826abstractbackground multiple sclerosis ms chronic inflammatory disease central nervous system patients ms experience wide range physical cognitive dysfunctions affect quality life promising training approach concurrently trains physical cognitive functions video gamebased physical exercising ie exergaming previous studies indicated exergames positive effects balance cognitive functions patients ms however still need specific usercentered exergames function motivating effective therapy tool patients ms studies investigating usability feasibilityobjective aim interdisciplinary research project develop usable feasible usercentered exergames pressuresensitive plate dividat senso incorporating theoretical backgrounds movement sciences neuropsychology game research well participatory design processesmethods focus groups patients therapists set define usercentered design process followed field testing newly developed exergame concepts two sequential usability feasibility studies conducted patients ms first study included single exergaming session followed measurements first second studies prototypes iterated based findings second study ran 4 weeks 12 trainings per week measurements taken intervention study participants answered system usability scale sus 10 items 5point likert scale score range 0100 interview questions second study participants answered game experiencerelated questionnaires flow short scale fss 13 items 7point likert scale score range 17 game flow questionnaire 17 items 6point likert scale score range 16 mixed methods used analyze quantitative qualitative dataresults first study n16 usability acceptable median sus score 713 iqr 588800 second study n25 median sus scores 897 iqr 788950 825 iqr 775900 thus significant decrease observed training z2077 p04 r042 moreover high values observed overall fss pre median 59 iqr 4664 post median 58 iqr 5462 overall game flow questionnaire pre median 50 iqr 4753 post median 51 iqr 4953 significant decrease observed item perceived importance fss z2118 p03 r042 interviews revealed usercentered exergames usable well accepted enjoyable points reference identified future research developmentconclusions project revealed newly developed usercentered exergames usable feasible patients ms furthermore exergame elements considered development phase usercentered exergames patients ms future studies needed provide indications efficacy usercentered exergames patients mspmid33960956 doi102196 22826,0.0
neurocognitive empowerment addiction treatment neat study protocol randomized controlled trial background neurocognitive deficits ncds associated metacognition difficulties associated chronic substance use often delay learning change process necessary addiction recovery relapse prevention however cognitive remediation programs developed target ncds metacognition substance users study described herein aims investigate efficacy multicomponent neurocognitive rehabilitation awareness program termed neurocognitive empowerment addiction treatment neat neat fully manualized cartoonbased intervention involving psychoeducation cognitive practice compensatory strategies relevant across 10 major cognitive domains including aspects attention memory executive functions decisionmakingmethod designin singleblind randomized controlled trial rct 80 female opioid methamphetamine users will recruited addiction recovery program providing alternative incarceration women substance userelated offenses eight groups 912 participants will randomized neat treatmentasusual tau neat involves 14 90min sessions delivered twice weekly primary outcome change selfreported drug craving intervention using obsessive compulsive drug use scale secondary exploratory outcomes include additional psychological neurocognitive structural functional neuroimaging measures clinical measures will performed five time points pre postintervention 3 6 12month followup neuroimaging measures will completed pre postinterventiondiscussionthe present rct first study examine efficacy adjunctive neurocognitive rehabilitation awareness program addiction results study will provide initial information concerning potential clinical efficacy treatment well delineate neural mechanisms potentially targeted novel interventiontrial registrationclinicaltrialsgovnct03922646 registered 22 april 2019,0.0
concordance persons multiple sclerosis treating physician medication effects health status patient prefer adherence 2021 may 7 15939943 doi 102147 ppas291485 ecollection 2021abstractbackground number treatment options multiple sclerosis ms expanded alignment physician patient effects medication emerged important medication persistence discontinuationobjective evaluate physicianpatient agreement levels medication effect health statusmethods persons ms pwms n71 participated crosssectional study collecting satisfaction using treatment satisfaction questionnaire medication intention dis continue treatment global health perception physicians assessed response medication global health statusresults concordance pwms assessment medication effectiveness physicians assessment response medication health status edss r s 050 r s 057 r s 058 respectivelyconclusion significant concordance attests physicianpatient effective communication may contribute improved medication adherencepmid33994780 pmcpmc8114576 doi102147 ppas291485,0.0
serial tap test patients idiopathic normal pressure hydrocephalus impact cognitive function meaning background idiopathic normal pressure hydrocephalus inph characterized gait disturbance urinary incontinence cognitive decline symptoms potentially reversible treatment based cerebrospinal fluid shunting tap test tt used identify patients will benefit surgery procedure consists withdrawal 20 50 ml cerebrospinal fluid csf lumbar puncture lp symptoms triad tested improvement quality speed gait already recognized cognitive improvement depends several factors tests used time elapsed lp retesting number punctures serial punctures may trigger similar conditions external lumbar drainage eld organismobjectivethis study aimed identify serial punctures affect cognition increase sensitivity test consequently accuracy surgical indicationmethodssixtyone patients inph underwent baseline memory executive tests repeatedly following 2step tap test protocol 2stt two procedures 30 ml lumbar csf drainage separated 24h interval baseline scores inph patients compared 55 healthy controls intragroup postpuncture scores 2sttresultsthe group inph lower performance control group cognitive tests ravlt stroop cft farcowa fab mmse orientation mental control except forward digit span test p 0707 conducting lp procedures stroop test words colors errors ravlt stage a1 a6 b1 cft immediate delayed r scores equal control group p 005 inph group presented significant improvement first puncture mmse p 0031 stroop test points p 0001 second puncture subjects improved orientation mmse ravlt b1 stroop points words errors cft ir conclusionprogressive cognitive improvement occurred 2stt changes significant second lp cognitive domains except ravlt a7 encephalic alert system arousal seems participate early improvements observed 2stt second lp increased sensitivity drainage test detect changes cognitive variables consequently improved quality method,0.0
brain volume perception cognitive impairment people multiple sclerosis caregivers front neurol 2021 may 6 12636463 doi 103389 fneur2021636463 ecollection 2021abstractbackground cognitive impairment ci common people multiple sclerosis pwms assessment ci based neuropsychological tests accurate anamnesis involving patients caregivers cg study aimed assess complex interplay selfperception ci objective ci brain atrophy ms patients also exploring possible differences ci evaluated caregivers methods relapsing pwms enrolled study subjects underwent neuropsychological examination using brief cognitive assessment multiple sclerosis bicams evaluation selfreported cognitive status using patientversion multiple sclerosis neuropsychological questionnaire pmsnq depression anxiety also evaluated using back depression inventoryversion ii bdiii zung anxiety scale brain mri images acquired brain volumes estimated patient enrolled spoke caregiver collected perception patients ci using msnq caregiver version results ninetyfive ms subjects caregivers enrolled ci detected 51 537 patients found significant correlation p 0001 bicams t scores lower whole brain rho 051 gray matter rho 054 cortical gray matter rho 051 volumes lower pmsnq rho 031 cgmsnq rho 041 scores multivariate logistic regression showed pmsnq related patients anxiety evaluate zung score p 0001 cgmsnq patients brain volume p 001 conclusion data confirm neuropsychological evaluation results related perception ci brain volume measures highlight importance caregivers perception cognitive assessment pwmspmid34025550 pmcpmc8136416 doi103389 fneur2021636463,0.0
hormones experimental autoimmune encephalomyelitis eae animal models transl neurosci 2021 may 6 12 1 164189 doi 101515 tnsci20200169 ecollection 2021 jan 1abstractmultiple sclerosis ms inflammatory demyelinating disease central nervous system cns activated immune cells attack cns cause inflammation demyelination etiology ms still largely unknown interaction hormones immune system plays role disease progression mechanisms occurs incompletely understood several vitro vivo experimental also clinical studies addressed possible role endocrine system susceptibility severity autoimmune diseases although several demyelinating models experimental autoimmune encephalomyelitis eae oldest commonly used model ms laboratory animals enables researchers translate findings eae human evidences imply great heterogeneity susceptibility induction method induction response various immunological pharmacological interventions led conflicting results role specific hormones eae model review address role endocrine system eae model provide comprehensive view better understanding interactions endocrine immune systems various models eae open ground detailed studies field considering comparing results models used previous studiespmid34046214 pmcpmc8134801 doi101515 tnsci20200169,1.0
identification neutrophil 2integrin lfa1 potential mechanistic biomarker ancaassociated vasculitis via microarray validation analyses background leukocyte activation antineutrophil cytoplasmic antibody anca subsequent leukocyteendothelium interaction play key role development endothelial damage ancaassociated vasculitis aav contrast leukocyte activation exact role leukocyteendothelium interaction via integrin remains unclear performed microarray validation analyses explore association expression levels lymphocyte functionassociated antigen1 lfa1 clinical characteristics patients aavmethodswe performed gene set enrichment analysis gsea identify functional gene sets differentially expressed patients aav types vasculitis healthy controls hcs flow cytometry performed validate gsea results treatmentnave patients monitored 24 weeks treatment examine role lfa1 neutrophilendothelium interaction performed leukocyte adhesion transmigration assay using peripheral blood human umbilical vein endothelial cells huvecs resultsgsea revealed molecular pathways involving integrinrelated genes significantly upregulated patients aav compared patients types vasculitis hcs flow cytometry revealed percentage neutrophils expressing lfa1 significantly higher patients aav largevessel vasculitis polyarteritis nodosa hcs lfa1 levels neutrophils higher patients mpoancapositive expression positive pr3anca expression correlated peripheral eosinophil count serum rheumatoid factor titre serum creactive protein levels vasculitis activity score systemic chest components 24 weeks treatment including prednisolone cyclophosphamide rituximab azathioprine methotrexate tacrolimus neutrophil lfa1 expression remained high nonresponder patients decreased responder patients vitro assay showed leukocyte migration toward huvecs dependent interaction lfa1 intercellular adhesion molecule1 icam1 migration leukocytes inhibited blocking adhesion lfa1 icam1conclusionsthe expression lfa1 neutrophils increased patients aav neutrophil lfa1 levels correlate clinical features aav inhibiting adhesion lfa1 icam1 impedes neutrophilendothelium interaction may therapeutic role aav,0.0
multiple sclerosis biomarker discoveries proteomics metabolomics approaches biomark insights 2021 may 6 1611772719211013352 doi 101177 11772719211013352 ecollection 2021abstractmultiple sclerosis ms autoimmune inflammatory disorder central nervous system cns resulting demyelination axonal loss brain spinal cord precise pathogenesis etiology complex disease still mystery despite many studies aimed identify biomarkers protein marker yet approved ms urgently needed biomarkers clarify pathology monitor disease progression response treatment prognosis ms proteomics metabolomics analysis powerful tools identify putative novel candidate biomarkers different human compartments analysis using proteomics metabolomics bioinformatics approaches generated new information clarification ms pathology elucidating mechanisms disease finding new targets monitoring treatment response overall omics approaches can develop different therapeutic diagnostic aspects complex disorders multiple sclerosis biomarker discovery personalized medicinepmid34017167 pmcpmc8114757 doi101177 11772719211013352,1.0
phakomatoses endocrine gland tumors noteworthy rare associations front endocrinol lausanne 2021 may 6 12678869 doi 103389 fendo2021678869 ecollection 2021abstractphakomatoses encompass group rare genetic diseases von hippellindau syndrome vhl neurofibromatosis type 1 nf1 tuberous sclerosis complex tsc cowden syndrome cs disorders due molecular abnormalities raspi3kaktmtor pathway nf1 tsc cs hypoxia sensing vhl phakomatoses share phenotypic traits neurological ophthalmological cutaneous features patients diseases also predisposed developing multiple endocrine tissue tumors eg pheochromocytomas paragangliomas frequent vhl nf1 forms phakomatoses except cs may associated digestive neuroendocrine tumors rarely thyroid cancer pituitary parathyroid adenomas reported susceptibilities noteworthy occurrence rate prognosis management differ slightly sporadic forms aim review summarize current knowledge endocrine glands tumors associated vhl nf1 tsc cs especially neuroendocrine tumors pheochromocytomas paragangliomas particularly detail recent advances concerning prognosis management especially parenchymasparing surgery medical targeted therapies mtor mek hif2 inhibitors shown truly encouraging resultspmid34025587 pmcpmc8134657 doi103389 fendo2021678869,0.0
conditional knockout tsc1 rortexpressing cells induces brain damage early death mice background tuberous sclerosis complex 1 tsc1 known regulate development function various cell types rort critical transcription factor immune system however whether tsc1 participates regulating rortexpressing cells remains unknownmethodswe generated mouse model tsc1 conditionally deleted rortexpressing cells tsc1rort study role rortexpressing cells tsc1 deficiency brain homeostasisresultstype 3 innate lymphoid cells ilc3s tsc1rort mice displayed normal development function mice showed normal th17 cell differentiation however tsc1rort mice exhibited spontaneous tonicclonic seizures died 4 6 weeks birth age 4 weeks mice tsc1 specifically knocked rortexpressing cells cortical neuron defects hippocampal structural abnormalities notably overactivation neurons astrogliosis observed cortex hippocampus tsc1rort mice moreover expression amino butyric acid gaba receptor brains tsc1rort mice decreased gaba supplementation prolonged lifespan mice extent experiments revealed presence group rare rortexpressing cells high metabolic activity mouse brainconclusionsour study verifies critical role previously unnoticed rortexpressing cells brain demonstrates tsc1 signaling pathway rortexpressing cells important maintaining brain homeostasis,0.0
simultaneous rupture two renal artery aneurysms patient tuberous sclerosis complex j vasc surg cases innov tech 2021 may 6 7 2 364367 doi 101016 jjvscit202104004 ecollection 2021 junabstracttuberous sclerosis complex tsc autosomal dominant multisystem neurocutaneous genetic condition characterized tscassociated neuropsychiatric disorders epilepsy tumors angiomyolipoma multiple organs skin lungs kidneys tsc also associated development aneurysms medium large arteries including renal arteries condition will usually diagnosed early life active surveillance required tumor aneurysm growth prevent lifethreatening events presented case 41yearold patient tsc previously diagnosed patient presented retroperitoneal hematoma secondary rupture two left renal artery branch aneurysms likely developed within angiomyolipomapmid34136727 pmcpmc8176208 doi101016 jjvscit202104004,0.0
serum shortchain fatty acids associations inflammation newly diagnosed patients multiple sclerosis healthy controls front immunol 2021 may 6 12661493 doi 103389 fimmu2021661493 ecollection 2021abstractmultiple sclerosis ms chronic immunemediated disease characterized demyelination neuroaxonal damage central nervous system etiology complex still fully understood accumulating evidence suggests gut microbiota metabolites influence ms pathogenesis shortchain fatty acids scfas acetate propionate butyrate metabolites produced gut microbiota fermentation indigestible carbohydrates scfas kynurenine metabolites shown important immunomodulatory properties propionate supplementation ms patients associated longterm clinical improvement however underlying mechanisms action importance ms remain incompletely understood analyzed serum levels scfas performed targeted metabolomics relation biomarkers inflammation clinical mri measures newly diagnosed patients relapsingremitting ms first disease modifying therapy healthy controls hcs demonstrated serum acetate levels nominally reduced ms patients compared hcs ratios acetate butyrate acetate propionate + butyrate significantly lower ms patients multivariate analysis orthogonal partial least squares discriminant analysis oplsda mentioned ratios acetate levels correlated negatively proinflammatory biomarker ifng indicating inverse relation acetate inflammation contrast proportion butyrate found higher ms patients multivariate analysis butyrate valerate correlated positively proinflammatory cytokines ifng tnf suggesting complex bidirectional regulatory properties scfas branched scfas inversely correlated clinical disability nominal significance level otherwise scfas correlate clinical variables mri measures signs alteration kynurenine pathway ms butyrate positively correlated immunomodulatory metabolite 3hydroxyanthranilic acid variables influenced separation ms hcs nfl arg1 il1r1 dribose 5phosphate pantothenic acid dglucuronic acid conclusion provide novel results rapidly evolving field emphasizing complexity interactions scfas inflammation therefore studies required clarify issues supplementation scfas can widely recommendedpmid34025661 pmcpmc8134701 doi103389 fimmu2021661493,1.0
mesenchymal stem nonstem cell surgery rescue regeneration glaucomatous optic neuropathy background glaucomatous optic neuropathy gon anatomofunctional impairment optic nerve triggered glaucoma recently growth factors gfs shown produce retinal neuroenhancement suprachoroidal autograft mesenchymal stem cells mscs limoli retinal restoration technique lrrt proven achieve retinal neuroenhancement producing gf directly choroidal space retrospectively registered clinical study investigated visual function changes patients gon treated lrrtmethodstwentyfive patients 35 eyes gon progressive disease conditions included study patient underwent comprehensive ocular examination including analysis best corrected visual acuity bcva far near visus sensitivity maia microperimetry study spectral domainoptical coherence tomography sdoct patients divided two groups control group consisting 21 eyes average age 722 years range 5083 lrrt group consisting 14 eyes average age 674 range 5084 resultsafter 6 months bcva closeup visus microperimetric sensitivity significantly improved lrrttreated group p005 whereas mean increases statistically significant controls p05 conclusionspatients gon treated lrrt showed significant increase visual performance vp bcva sensitivity improvement residual closeup visus comparison lrrt results control group studies will needed establish actual significance reported findings,0.0
vivo induction regulatory t cells via ctla4 signaling peptide control autoimmune encephalomyelitis prevent disease relapse adv sci weinh 2021 may 5 8 14 2004973 doi 101002 advs202004973 ecollection 2021 julabstractregulatory t cells play key role immune tolerance selfantigens thereby preventing autoimmune diseases however drugs targeting treg cells approved clinical trials yet chimeric peptide generated conjugation cytoplasmic domain ctla4 ctctla4 dnp2 intracellular delivery dnp2ctctla4 evaluated foxp3 expression th0 th1 treg th17 differentiation dependent tgf lysine motif ctctla4 tyrosine motif required foxp3 expression treg induction amelioration experimental autoimmune encephalomyelitis eae transcriptome analysis reveals dnp2ctctla4treated t cells express treg transcriptomic patterns properties suppressive functions addition molecular interaction lysine motif ctctla4 pkc critical foxp3 expression although ctla4ig dnp2ctctla4 treatment vivo ameliorated eae progression dnp2ctctla4 requires treg cells inhibition disease progression prevention relapse furthermore ctla4 signaling peptide able induce human tregs vitro vivo well peripheral blood mononuclear cells pbmcs multiple sclerosis patients results collectively suggest chimeric ctla4 signaling peptide can used successful induction regulatory t cells vivo control autoimmune diseases multiple sclerosispmid34306974 pmcpmc8292875 doi101002 advs202004973,0.0
systematic review incidence risk factors prognosis acute exacerbation systemic autoimmune diseaseassociated interstitial lung disease abstractintroductionacute exacerbation ae devastating phenomenon reported complicated systemic autoimmune diseaseassociated interstitial lung disease ild aim study investigate incidence prognosis ae systemic autoimmune diseaseild clarify relevant clinical information predictive outcomesmethodthis study designed systematic review metaanalysis primary study except case report reported incidence prognosis ae systemic autoimmune diseaseild eligible review electronic databases medline embase searched 2002 23 february 2020 two reviewers independently selected eligible reports extracted relevant data risk bias individual studies assessed similarly incidence prognosis disease analysed qualitatively univariate results risk prognostic factors combined feasibleresultsout total 2662 records 24 studies eligible total 420 subjects 457 men developed ae systemic autoimmune diseaseild two major underlying systemic autoimmune diseases rheumatoid arthritis 342 polymyositis dermatomyositis 319 frequency ranged 43 329 incident rate 319 577 per 100 patientyears allcause mortality 300 583 90 days age initial presentation significantly associated development ae systemic autoimmune diseaseild hr 122 95ci 105150 percentage predicted diffusing capacity lung carbon monoxide dlco also significantly associated development disease hr 095 95ci 090100 097 95ci 095099 partial pressure arterial oxygen fraction inspired oxygen ratio pao2 fio2 ae significantly associated allcause mortality ae systemic autoimmune diseaseild hr 099 95ci 098099 conclusionae systemic autoimmune diseaseild uncommon demonstrated dismal prognosis age initial presentation dlco deemed risk factors pao2 fio2 ae considered prognostic factor diseaseregistration crd42019138941,0.0
exploring gutbrain axis control cns inflammatory demyelination immunomodulation bacteroides fragilis#39 polysaccharide front immunol 2021 may 5 12662807 doi 103389 fimmu2021662807 ecollection 2021abstractthe symbiotic relationship animals resident microorganisms profound effects host immunity human microbiota comprises bacteria reside gastrointestinal tract involved range inflammatory autoimmune diseases gut microbiotas immunomodulatory effects extend extraintestinal tissues including central nervous system cns specific symbiotic antigens responsible inducing immunoregulation isolated different bacterial species polysaccharide psa bacteroides fragilis archetypical molecule hostmicrobiota interactions studies shown psa beneficial effects experimental disease models including experimental autoimmune encephalomyelitis eae widely used animal model multiple sclerosis ms furthermore vitro stimulation psa promotes immunomodulatory phenotype human t cells isolated healthy ms donors review discuss current understanding interactions gut microbiota host context cns inflammatory demyelination immunomodulatory roles gut symbionts specifically also discuss immunomodulatory effects b fragilis psa gutbrain axis therapeutic potential ms elucidation molecular mechanisms responsible microbiotas impact host physiology offers tremendous promise discovering new therapiespmid34025663 pmcpmc8131524 doi103389 fimmu2021662807,1.0
knee pain trajectories 18months nonhispanic black nonhispanic white adults risk knee osteoarthritis background pain hallmark symptom knee osteoarthritis oa varies widely across individuals previous research demonstrated fluctuating stable pain trajectories knee oa using various time periods changes pain assessed quarterly ie 3month intervals knee oa relatively unknown current study aimed investigate temporal variations pain one half year period 18 months based quarterly characteristic pain assessments examine differences pain patterns sociodemographic baseline pain characteristicsmethodsthe sample included prospective cohort 188 participants mean age 58 years 63 female 52 nonhispanic black risk knee oa ongoing multisite investigation ethnic race group differences knee pain intensity selfreported baseline quarterly an18month period baseline pain assessment also included frequency duration total number pain sites groupbased trajectory modeling used identify distinct pain trajectories multinomial logistic regression used examine associations sociodemographic characteristics risk factors pain trajectory groupsresultspain trajectories relatively stable among sample adults knee pain four distinct pain trajectories emerged overall sample largest proportion participants 351 classified moderatehigh pain group significant relationships age education income ethnicity race trajectory group younger less educated lower income nonhispanic black participants greater representation highest pain trajectory groupconclusionspain remained stable across one halfyear period adults risk knee osteoarthritis based quarterly assessments certain sociodemographic variables eg ethnicity race education income age may contribute increased risk experiencing greater pain,0.0
anticancer drugs repurposed alzheimers disease systematic review background relationship cancer dementia triggering growing research interest several preclinical studies provided biological rationale repurposing specific anticancer agents alzheimers disease ad growing number research protocols testing efficacy safety tolerability patients admethodsthe aim present systematic review provide overview repurposing approved anticancer drugs clinical trials ad considering ongoing completed research protocols phases parallel systematic literature review conducted pubmed isi web cochrane library identify published clinical studies repurposed anticancer agents adresultsbased structured search clinicaltrialsgov eudract databases identified 13 clinical trials testing 11 different approved anticancer agents five tyrosine kinase inhibitors two retinoid x receptor agonists two immunomodulatory agents one histone deacetylase inhibitor one monoclonal antibody ad continuum systematic literature search led identification five published studies one phase three phase ii one phase iib iii reporting effects antitumoral treatments patients mild cognitive impairment ad dementia clinical findings methodological characteristics studies described discussedconclusionanticancer agents triggering growing interest context repurposed therapies ad several clinical trials underway data expected available near future date data emerging published clinical studies controversial promising results emerging preclinical studies identified research protocols confirmed extended larger adequately designed highquality clinical trials,0.0
emerging treatments scleroderma systemic sclerosis fac rev 2021 may 5 1043 doi 1012703 r 1043 ecollection 2021abstractsystemic sclerosis ssc connective tissue disease characterized progressive fibrosis skin internal organs significant clinical sequelae management ssc cutaneous disease remains challenging often driven extracutaneous manifestations methotrexate typical firstline therapy patients early progressive cutaneous disease however patients diffuse progressive skin disease inflammatory arthritis methotrexate rituximab monotherapy considered firstline therapy patients concomitant myositis includes methotrexate intravenous immunoglobulin ivig patients cutaneous findings interstitial lung disease studies suggested efficacy mycophenolate mofetil rituximab secondline therapies including uva1 phototherapy ivig rituximab can considered patients disease refractory firstline treatments clinical trials investigating utility emerging therapies abatacept tocilizumab treatment ssc way preliminary results promising nonetheless patients ssc benefit gentle skincare regimen alleviate pruritis commonly reported symptom additional cutaneous manifestations ssc include telangiectasias calcinosis cutis microstomia raynauds phenomenon telangiectasia may managed camouflage techniques pulse dye laser intense pulse light calcinosis cutis therapy guided size calcium deposits although treatment options limited mouth augmentation oral stretching exercises recommended patients reduced oral aperture raynauds phenomenon treated combination lifestyle modification calcium channel blockers amlodipine overall ssc clinically heterogenous disease affects multiple organ systems providers assess extracutaneous involvement use evidencebased recommendations select appropriate therapy patients sscpmid34131653 pmcpmc8170563 doi1012703 r 1043,0.0
identification rpd3 novel epigenetic regulator drosophila fig 4 charcotmarietooth diseasecausing gene neuroreport 2021 may 5 32 7 562568 doi 101097 wnr0000000000001636abstractmutations factorinducedgene 4 fig 4 gene associated multiple disorders including charcotmarietooth disease cmt epilepsy polymicrogyria yunisvarn syndrome amyotrophic lateral sclerosis wide spectrum disorders associated fig 4 may related dysregulated epigenetics using gene expression omnibus found hdac1 binds fig 4 gene locus genome human cd4+ t cells rpd3 wellknown drosophila homolog human hdac1 previously established drosophila models targeting drosophila fig 4 dfig 4 exhibited defective locomotive ability abnormal synapse morphology neuromuscular junctions enlarged vacuoles fat body aberrant compound eye morphology genetic crossing experiments followed physiological immunocytochemical analyses revealed rpd3 mutations suppressed defects induced dfig 4 knockdown demonstrated rpd3 important epigenetic regulator dfig 4 suggesting inhibition hdac1 represses pathogenesis fig 4associated disorders including cmt defects epigenetic regulators hdac1 may also explain diverse symptoms fig 4associated disorderspmid33850086 doi101097 wnr0000000000001636,0.0
reduction pericyte coverage leads bloodbrain barrier dysfunction via endothelial transcytosis following chronic cerebral hypoperfusion background chronic cerebral hypoperfusion cch leading cause cerebral small vessel disease csvd cch strongly associated bloodbrain barrier bbb dysfunction white matter lesions wmls csvd however effects cch bbb integrity components cellular molecular mechanisms underlying effects bbb dysfunction remain elusive whether maintaining bbb integrity can reverse cchinduced brain damage also exploredmethodsin study established rat model csvd via permanent bilateral common carotid artery occlusion 2vo mimic chronic hypoperfusive state csvd progression bbb dysfunction components bbb assessed using immunostaining western blotting transmission electron microscopy tem rna sequencing also observed protective role imatinib tyrosine kinase inhibitor bbb integrity neuroprotective function following cch data analyzed using oneway twoway anovaresultswe noted transient yet severe breakdown bbb corpus callosum cc following cch bbb severely impaired early 1 day postoperation severely impaired 3 days postoperation bbb breakdown preceded neuroinflammatory responses formation wmls moreover pericyte loss associated bbb impairment accumulation serum protein mediated increased endothelial transcytosis cc rna sequencing also revealed increased transcytosis genes expression bbb dysfunction led brain damage regulation tgf smad2 signaling furthermore imatinib treatment ameliorated serum protein leakage oligodendrocyte progenitor cell opc activation endothelial transcytosis microglial activation aberrant tgf smad2 signaling activationconclusionsour results indicate reduced pericyte coverage leads increased bbb permeability via endothelial transcytosis imatinib executes protective role bbb integrity via inhibition endothelial transcytosis maintenance bbb integrity ameliorates brain damage regulation tgf smad2 signaling following cch therefore reversal bbb dysfunction may promising strategy csvd treatment,1.0
anterior hybrid construction multilevel cervical disc disease spondylotic spinal stenosis surgical results factors affecting adjacent segment problems abstractobjectivewe aimed evaluate reliability radiological outcomes impacts anterior cervical hybrid construction adjacent segments multilevel cervical degenerative disc disease mcddd spondylotic spinal stenosis sss methodsa retrospective analysis performed using data extracted medical files 195 patients 105 males 90 females mean age 477 years 2008 2018 patients underwent anterior cervical hybrid construction symptomatic contiguous least 2level cervical degenerative disc diseases cervical spondylosis clinical radiological data including neck disability index ndi visual analogue scale vas local cervical degenerative disk disease adjacent segments magnetic resonance imaging mri views complications reviewedresultsthe mean clinical radiological followup 452 months range 24 102 radiculopathy myelopathy main clinical problems patients mean vas scores hc arm pain 74 08 preoperatively 28 06 1 month surgery 23 06 6 months surgery 18 06 12 month surgery 16 06 24 months surgery mean ndi scores mean sd hc significantly improved surgery admission 572 55 1 month surgery 2735 53 6 month surgery 2143 28 12 months surgery 219 23 24 months surgery 206 26 p 0006 hoarseness dysphagia common complications osteophyte formation frequent radiographic changeconclusionanterior cervical hybrid construction appears acceptable option management multilevel cervical degenerative disc diseases spondylotic spinal stenosis,0.0
translating human microbiome path improving health translating human microbiome health disease requires detailed information microbial memberfrom individual annotated genomes community functional dynamics relationships host toward goal phylogenetic descriptions microbiome evolving mechanistic analyses recent years seen dramatic rise metagenomic metabolomic studies using microbialdriven pathologies models understand hostmicrobiome interactions studies charting communitywide ecological maps provide insight microbial determinants health disease layering impacts microbiome different life stages although much known early microbiome development trajectories aging later life require characterizationthe microbiome impacts every organ system aspect physiology often asyetunknown mechanisms moreover influence microbiome extends beyond local environment neuroactive molecules produced gut commensals reach brain mediate mood depression mental illness 1 understanding principles govern healthy microbiome establishes framework interrogating perturbations associated disease diet developing interventional strategies unlike genome microbiome dynamic reflection health status can modified therefore represents largely untapped reservoir opportunity understand exploit mechanisms influence human physiologythis special issue genome medicine highlights advances made understanding strain diversity microbial biochemistry disease risk clinical outcomes editorial highlight key areas recent progress made field toward translating microbiome defining many pathways modulate host biologycomprehensive maps single microbemetagenomic sequences provide framework generate testable mechanistic hypotheses however functional validation limited availability culturable isolates strain collections assembled aiming capture breadth diversity within microbiome underrepresent strainspecific functional diversity obstacle circumvented part computational advancements comparative genomics platforms can analyze single bacterial class map genetic diversity phenotypes identify potential competitive fitness genes quantification highly related strains 2 approach highlights value comparative genomics mechanistic analyses unculturable microbes impact human healthmicrobiome t cellsrecently learnt subsets microbiomereactive t cells characteristic health various diseases knowledge microbial antigens incomplete 3 computational tools accelerating progress antigen discovery immunodominance characterizations t cell receptors functional phenotypes predicting antigen binding mhc molecules instance powerful approach interrogate features immunogenicity specificity t cell responses bota bacteria originated t cell antigen predictor uses genomic sequences generate candidate mhciirestricted epitopes based accessibility criteria coupled highthroughput validation recognition t cell receptors provides platform identify immunodominant epitopes detailed molecular characterizations responses induced bacterial isolates t cell subsets harvested healthy disease tissues will aid future functional analysesadaptive immunity additionally affected microbial metabolites recent work revisited effects bacterially modified bile acids t cell biology lithocholic acid lca derivatives found regulate differentiation naive t cells treg th17 cells balance plays critical role inflammatory bowel diseases ibd 4 network microbial bile acid metabolites shown maintain specific treg population colon ameliorates gut inflammation 5 secondary bile acid 3hydroxydeoxycholic acid isodca promoted treg generation reducing immunostimulatory properties dendritic cells 6 global scale impact microbiome host chemistry revealed comparing metabolomes germfree specificpathogenfree mice uncovered previously unknown bile acid conjugates enriched ibd cystic fibrosis patients 7 toward unraveling microbial pathways responsible bile acid metabolism set six enzymes found required derive dca conferred ability produce dca lca expressed commensal synthesize molecules naturally 8 thus potential modulating metabolite levels host increases knowledge microbial biosynthetic pathways expandsmicrobiome dietdietary fibers modulate composition function microbiome shaping hostmicrobiome interactions fiberrich diets maintain healthy diverse microbiome lead beneficial metabolites shortchain fatty acids scfas promote mucus antimicrobial peptides production well maintain intestinal barrier integrity robust immunity fiberpoor diets reduce diversity alter microbial functions impairing host physiology increasing susceptibility infection chronic inflammation interventional increases dietary glycans fructooligosaccharides polydextrose shown cause quantifiable consistent microbiome responses 9 importantly decreases bacterially fermented metabolites glycans scfas associated igemediated food allergy providing example dietarydriven microbiota changes can influence human health disease 10 specific microbial commensals linked beneficial health effects dependent diet example prevotella copri correlated improved glucose insulin tolerance subjects consume high fiber diet 11 12 two foundational studies resolved genomic functional variation prevotella copri presented metagenomic analyses defining four carbohydratemetabolizing clades highly prevalent nonindustrialized populations typically highfiber diets functional analyses confirmed isolates clade utilize distinct sets plantderived polysaccharides thus increasing interest restoration healthy state potentially dietary interventions utilizing microbial carbohydrateactive enzymes cazymes replace metabolic activity lost dietdependent microbiome changesmicrobiome disease pathophysiologydiscoveries microbiomeassociated diseases point toward mechanisms underlying pathophysiology addressing concurrent increases autoimmune allergic disease rates hygiene hypothesis posits early childhood exposure certain microbes contributes immune development protects diseases test longitudinal study followed children genetically predisposed autoimmunity birth age three neighboring countries 13 infants born finland estonia earlyonset autoimmunity common exposed lipopolysaccharide lps primarily bacteroides highly abundant microbiomes infants born russian karelia autoimmunity less prevalent exposed structurally distinct lps escherichia coli study demonstrated bacteroides lps inhibits innate immune activation e coli lps providing evidence early life colonization immunesilencing microbiota may hinder immune education enhance susceptibility autoimmune diseasegain lossoffunction mutations c9orf72 contribute neurodegenerative diseases including amyotrophic lateral sclerosis als microbiomes als patients differ unaffected individuals recent evidence suggests interactions c9orf72 microbiome influence inflammatory responses within nervous system latter stemmed observation despite identical genetic backgrounds c9orf72deficient mice reared separate facilities harbored distinct microbiota displayed marked differences disease severity reduction immunestimulating bacteria protected c9orf72deficient mice neuroinflammation early mortality even initial onset 14 contrast disease exacerbated sod1g93a mouse model als lacking microbiome treated antibiotics 15 findings underscore importance interactions genetics microbiome multifactorial diseasesthe microbiome influences cancer onset progression response therapy effects can exerted indirectly release bioactive molecules circulation also possible tumor microenvironment support microbiome bacteria long detected tumors small biomass microenvironment made challenging exclude possibility contamination recent analysis surveyed bacteria primary tumors adjacent normal tissue across seven cancer types body sites exposed protected microbes 16 tumor type displayed unique microbial profile breast tumors harboring richest diverse microbiome microbes predicted metabolic functions associated clinical features smoking status response therapy another example using integrated multiomics hepatocellular carcinoma patients identified changes tumor immune microenvironment caused gut microbiota via serum bile acids suggesting gut microbes may used biomarkers clinical features outcomes 17 although determining mechanistic links remains challenge studies represent important first stepsthe missing microbiome global conservancycurrent efforts building extensive biobanks human gut isolates corresponding multiomic data advance mechanistic research preserve expand understanding microbiome biodiversity across communities worldwide research date largely centers industrialized populations providing little insight microbiomes nonindustrialized populations often diverse moreover therapies based targeted industrialized microbiomes might ineffectual even detrimental populations longitudinal microbiome analyses hadza indigenous huntergatherer society illuminated important roles played gut microbes risk extinction industrialization 18 hadza diet follows distinct seasons reflected microbiome composition functional capacity particularly cazymes taxa fluctuating season differentiated hadza industrialized populations suggesting presence dynamic microbes decreased result modern lifestyles isolate collections comprising strains industrialized nonindustrialized populations valuable determine impact lifestyle microbiome composition diversity also investigate adaptation within bacterial genomes higher rates horizontal gene transfer found microbiomes industrialized populations indicating microbes acquire new functionalities suited host lifestyle 19 future directionshuman cohort studies will continue integral translating microbiome health disease treatmentnaive cohorts longitudinal studies revealed important alterations microbiome community structure function ibd 3 serve templates microbiomeassociated diseases early analysis treatmentnaive pediatric crohns disease cd patients defined microbial axis strongly associated disease status amplified antibiotic treatment axis established first link oral microbes chronic intestinal inflammation data cohort also correlated early antitnf therapy reduced risk certain complications led development riskstratification model studies treatmentnaive pediatric ulcerative colitis uc patients linked compositional temporal microbiome changes disease course response therapy integrative human microbiome project catalogued longitudinal taxonomic functional biochemical shifts ibd identifying metabolites exclusively ibd patients uncovering distinct microbial enrichments cd uc 20 microbial clinical factors implicated human cohort studies will inform optimal treatment strategies guide clinical translations microbiomemultiomic data exposed extensive microbial dark matter within microbiome much unculturable microbes metabolic capabilities remains unknown new computational biochemical approaches enabling characterization unannotated molecules next steps will resolve human metabolome host microbial co metabolites initially derived host modified microbes vice versa build chemical libraries can tested functional assays complete annotation microbes genes proteins metabolites within human microbiome will essential hypothesisbased functional studies reveal biological mechanisms work health diseasewhile promising route improvement human health microbiomebased therapeutics face several current challenges one need study immunomodulatory molecules bioactives derived microbes physiological concentrations deep mechanistic understandings need developed particular emphasis potential pleiotropic effects example single microbial metabolite may bind multiple host receptors distinct often cell typespecific biological outcome stimulation thresholds determined signal strength duration might also dictate host responses synergistic antagonistic effects observed reductionist models appear complex contexts emphasize critical importance conducting functional studies simple systems mono cocultures well sophisticated models closely resemble tissues lastly pharmacokinetic processes administration absorption distribution metabolism excretion need considered evaluating metabolites microbes therapeutics future microbiomebased precision medicine will rely extensive hypothesisbased functional work well full consideration complexities microbes hosts order improve human health,0.0
proteomic analysis human frontal temporal cortex using itraqbased 2d lcms ms background human brain complex organ body important better understanding protein composition brain regions contributes pathogenesis associated neurological disordersmethodsin study comparative analysis frontal temporal cortex proteomes conducted isobaric tags relative absolute quantification itraq labeling twodimensional liquid chromatographytandem mass spectrometry 2d lcms ms brain protein taken relatively normal tissue avoided damage emergent surgery tbi traumatic brain injury patients admitted beijing tiantan hospital 2014 2017 eight cases included four frontal lobes 4 temporal lobes proteome analyzed proteins quantitated gene ontology go ingenuity pathway analysis ipa kyoto encyclopedia genes genomes kegg pathway analysis used analyze biological function identified proteins unchanged proteins differentially expressed proteins deps resultsa total number 2127 protein groups identified frontal temporal lobe proteomes total 1709 proteins quantitated frontal temporal cortex among 90 deps 14 proteins screened highly expressed temporal cortex including mapt sncg atp5if1 gap43 hspe1 stmn1 ndufs6 ldhb sncb ndufa7 mrps36 epdr1 cisd1 rala addition compared proteins expressed frontal cortex 14 proteins including edc4 nit2 vwf astn1 tgm2 ssb clu hba1 stom crp lrg1 saa2 s100a4 vtn low expression temporal cortex biological process enrichment showed unchanged proteins frontal temporal cortex mainly take part regulated exocytosis axon guidance vesiclemediated transport kegg pathway analysis showed unchanged proteins frontal temporal cortex mainly take part oxidative phosphorylation carbon metabolism huntingtons disease parkinsons diseaseconclusionsthe majority proteins unchanged frontal temporal cortex unchanged proteins closely related function among deps matp tau upregulated temporal cortex closely related alzheimers disease ad one targets treatment ad clu downregulated temporal cortex functions extracellular chaperone prevents aggregation nonnative proteins suggested temporal lobe may functional dumb area traditional view involved important neural metabolic circuits,0.0
diet obesity gut microbiome determinants modulating metabolic outcomes nonhuman primate model objective study increase understanding complex interactions diet obesity gut microbiome adult female nonhuman primates nhps subjects consumed either western n,0.0
engineered neurovascular unit modeling neuroinflammation biofabrication 2021 apr 13 doi 101088 17585090 abf741 online ahead printabstractthe neurovascular unit nvu comprises multiple types brain cells including brain endothelial cells astrocytes pericytes neurons microglia oligodendrocytes cell type contributes maintenance molecular transport barrier brain tissue homeostasis several disorders diseases central nervous system including neuroinflammation alzheimers disease stroke multiple sclerosis associated dysfunction nvu result increased demand development nvu vitro models present threedimensional 3d immortalized human cellbased nvu model generated organizing brain microvasculature collagen matrix embedded six different types cells comprise nvu surrounding perfusable brain endothelium six types nvucomposing cells demonstrated significant impact 3d coculture maturation barrier function supported cytokines secreted nvucomposing cells furthermore nvucomposing cells alleviated inflammatory responses induced lipopolysaccharides human cellbased nvu vitro model enable elucidation physiological pathological mechanisms human brain evaluation safety efficacy context highcontent analysis process drug developmentpmid33849004 doi101088 17585090 abf741,0.0
functional connectivity changes cerebral small vessel disease systematic review restingstate mri literature background cerebral small vessel disease csvd common neurological disease present ageing population associated increased risk dementia stroke damage white matter tracts compromises substrate interneuronal connectivity analysing restingstate functional magnetic resonance imaging fmri can reveal dysfunctional patterns brain connectivity contribute explaining pathophysiology clinical phenotypes csvdmaterials methodsthis systematic review provides overview methods results recent restingstate functional mri studies patients csvd following preferred reporting items systematic reviews metaanalysis prisma protocol systematic search literature performedresultsof 493 studies screened 44 reports identified investigated restingstate fmri connectivity context cerebral small vessel disease risk bias heterogeneity results moderate high patterns associated csvd included disturbed connectivity within intrinsic brain networks particular default mode dorsal attention frontoparietal control salience networks decoupling neuronal activity along anteriorposterior axis increases functional connectivity early stage diseaseconclusionthe recent literature provides evidence functional disconnection model cognitive impairment csvd suggest salience network might play hitherto underappreciated role model low quality evidence lack preregistered multicentre studies remain challenges overcome future,0.0
economics multiple sclerosis diseasemodifying therapies usa curr neurol neurosci rep 2021 may 5 21 7 28 doi 101007 s1191002101118xabstractpurpose review multiple sclerosis ms prevalent debilitating neuroinflammatory disease associated significant economic burden direct healthcare costs can average 70 000 year risen rapidly last decade driven escalating cost diseasemodifying therapies dmts despite growing number dmts annual increases price dmts commonly exceeded 10 last 15 years high cost ms dmts created economic hardships patients terms high outofpocket costs insurance companyinduced barriers although generic versions glatiramer acetate dimethyl fumarate provided lower cost options median annual price branded products currently exceeds 90 000 goal paper examine economic landscape ms dmts usarecent findings recent economic analyses provided new insights relative value dmts robust economic modeling studies suggest costs per qualityadjusted lifeyear dmts exceed commonly endorsed thresholds considered reasonable value usa higher efficacy lower net costs ocrelizumab alemtuzumab considered best value likely generic versions dimethyl fumarate glatiramer acetate also economically attractive dmts provide clinical benefit patients ms however high cost can financial burden impede access high dmt prices principal reason costeffectiveness studies indicated economic value dmts questionablepmid33948740 doi101007 s1191002101118x,0.0
mobilephonebased ediary derived patient reported outcomes association clinical disease activity psychological status quality life patients multiple sclerosis plos one 2021 may 5 16 5 e0250647 doi 101371 journalpone0250647 ecollection 2021abstractbackground applicability mobile digital technology promote clinical care people multiple sclerosis pwms gaining increased interest part implementation patientcentered approaches aimed assessing adherence smartphonebased ediary designed collect patientreported outcomes pros secondary objectives evaluate construct predictive validity ediary derived pros explore various factors associated changes pros timematerials methods observational cohort study patients downloaded ms tailored ediary personal smartphones report pros enquired monthly period one year smartphonebased application using previously validated tools ediary derived bodily function summary score ebf defined sum scores depicting vision limbs function pain bowl bladder dysfunction pseudobulbar affect spasticity multiple linear regression analysis covariance used determine association pros clinicianreported outcomes clinros disease activity quality life qol regression coefficient analysis used compare slope change ebf relapseresults 97 pwms downloaded ediary female 64 66 edss 3421 76 patients 78 completed 12month study period 53 patients 55 submitted 75 requested surveys anxiety negatively associated adherence periodic pros assessments ediary ediary derived pros significantly correlated corresponding functional system scores 038 r 08 p0001 ebf score significantly predicted qol 036 p 0001 edss change ebf score time independently associated occurrence ms relapse f 44 p 004 anxiety f 64 p 001 depression f 51 p 003 individual regression slopes ebf scores significantly higher prerelapse postrelapse 3033 vs 0820 p 0007 conclusion adherence pwms recording ediary collecting pros high changes ediary derived pros time predict clinical ms relapses group level thus carry potential usage clinical research well improved ms care real world settingpmid33951061 doi101371 journalpone0250647,0.0
evaluation cerebrospinal fluid glycoprotein nmb gpnmb potential biomarker alzheimers disease background alzheimers disease ad neurodegenerative disorder associated extracellular amyloid peptide deposition progressive neuron loss strong evidence supports neuroinflammatory changes activation astrocytes microglia cells important disease process glycoprotein nonmetastatic melanoma protein b gpnmb transmembrane glycoprotein recently associated emerging role neuroinflammation reported increased postmortem brain samples ad parkinsons disease patientsmethodsthe present study describes partial fit purpose validation commercially available immunoassay determination gpnmb levels cerebrospinal fluid csf assessed applicability gpnmb potential biomarker ad two different cohorts defined biomarkersupported clinical diagnosis neuroimaging amyloid positron emission tomography respectivelyresultsthe results indicated csf gpnmb levels distinguish ad controls neurological diseases correlated parameters aging csf ptau levelsconclusionsthe findings study support gpnmb csf valuable neurochemical diagnostic biomarker ad warrant studies employing healthy control individuals,0.0
author response effect ocrelizumab vaccine responses patients multiple sclerosis veloce study neurology 2021 may 4 96 18 870 doi 101212 wnl0000000000011868no abstractpmid34032593 doi101212 wnl0000000000011868,0.0
matrine treatment reduces retinal ganglion cell apoptosis experimental optic neuritis sci rep 2021 may 4 11 1 9520 doi 101038 s41598021890867abstractinflammatory demyelination axonal injury optic nerve hallmarks optic neuritis often occurs multiple sclerosis major cause visual disturbance young adults although high dose corticosteroids can promote visual recovery prevent permanent neuronal damage novel effective therapies thus required given recently defined capacity matrine mat quinolizidine alkaloid derived herb radix sophorae flavescens immunomodulation neuroprotection tested study effect matrine rats experimental autoimmune encephalomyelitis animal model multiple sclerosis mat administration started disease onset significantly suppressed optic nerve infiltration demyelination reduced numbers iba1+ macrophages microglia cd4+ t cells compared vehicletreated rats increased expression neurofilaments axon marker reduced numbers apoptosis retinal ganglion cells rgcs moreover mat treatment promoted akt phosphorylation shifted bcl2 bax ratio back towards antiapoptotic one mechanism therapeutic effect model taken whole results demonstrate mat attenuated inflammation demyelination axonal loss optic nerve protected rgcs inflammationinduced cell death mat may therefore potential novel treatment disease may result blindnesspmid33947942 doi101038 s41598021890867,1.0
reader response effect ocrelizumab vaccine responses patients multiple sclerosis veloce study neurology 2021 may 4 96 18 870 doi 101212 wnl0000000000011867no abstractpmid34032592 doi101212 wnl0000000000011867,0.0
plasma markers pulmonary hypertension subgroups correlate patient survival background recent studies provided evidence important contribution immune system pathophysiology pulmonary arterial hypertension pah chronic thromboembolic pulmonary hypertension cteph report investigated whether inflammatory profile pulmonary hypertension patients changes time correlates patient subgroups survivalmethods50 pah patients 16 idiopathic pah 24 connective tissue disease ctd pah 10 congenital heart disease chd pah 37 cteph patients 18 healthy controls hcs included study plasma inflammatory markers baseline 1year followup measured using elisas subsequently correlations hemodynamic parameters survival explored data sets subjected unbiased multivariate analysesresultsat diagnosis found plasma levels interleukin6 il6 chemokines cx3c motif legend cxcl9 cxcl13 ctdpah patients significantly increased compared hcs idiopathic pah patients levels tumor growth factor tgf il10 cxcl9 elevated compared hcs increased cxcl9 il8 concentrations cetph patients correlated significantly decreased survival suggesting cxcl9 il8 may prognostic markers one year treatment il10 cxcl13 tgf levels changed significantly pah subgroups cteph patients unbiased multivariate analysis revealed clustering ph patients based inflammatory mediators clinical parameters separate subgroups importantly multivariate analyses separated patients 3 years 3 years survival particular inflammatory mediators combined clinical parametersdiscussionour study revealed elevated plasma levels inflammatory mediators different pah subgroups cteph baseline 1year followup whereby cxcl9 il8 may prove prognostic markers cteph patients study exploratory hypothesis generating data indicate important role il8 cxcl9 chd cteph patients considering increased plasma levels observed correlation survivalconclusionin conclusion studies identified inflammatory signature clustered ph patients classificationindependent subgroups correlated patient survival,0.0
diagnosis treatment neurogenic dysphagia s1 guideline german society neurology abstractintroductionneurogenic dysphagia defines swallowing disorders caused diseases central peripheral nervous system neuromuscular transmission muscles neurogenic dysphagia one common time dangerous symptoms many neurological diseases important sequelae include aspiration pneumonia malnutrition dehydration affected patients often require longterm care exposed increased mortality based systematic pubmed research related original papers review articles international guidelines surveys diagnostics treatment neurogenic dysphagia consensus process initiated included dysphagia experts 27 medical societiesrecommendationsthis guideline consists 53 recommendations covering first part whole diagnostic spectrum dysphagia specific medical history initial dysphagia screening clinical assessment refined instrumental procedures flexible endoscopic evaluation swallowing videofluoroscopic swallowing study highresolution manometry addition specific clinical scenarios captured among others management patients nasogastric tracheotomy tubes second part guideline dedicated treatment neurogenic dysphagia apart dietary interventions behavioral swallowing treatment interventions improve oral hygiene pharmacological treatment options different modalities neurostimulation well minimally invasive surgical therapies dealt withconclusionsthe diagnosis treatment neurogenic dysphagia challenging requires joined effort different medical professions evidence supporting implementation dysphagia screening rather convincing trials needed improve quality evidence refined methods dysphagia diagnostics particular different treatment options neurogenic dysphagia present article abridged translated version guideline recently published online https wwwawmforg uploads tx_szleitlinien 030111l_neurogenedysphagie_202005pdf,0.0
adhesion process biomimetic myelin membranes triggered myelin basic protein front chem 2021 may 4 9631277 doi 103389 fchem2021631277 ecollection 2021abstractthe myelin sheatha multidoublebilayer membrane wrapped around axonsis essential part nervous system enables rapid signal conduction damage complex membrane system results demyelinating diseases multiple sclerosis ms process myelin generated vivo called myelination study investigated adhesion process large unilamellar vesicles supported membrane bilayer coated myelin basic protein mbp using timeresolved neutron reflectometry aim mimic study myelination process membrane systems either lipidcomposition resembling native myelin standard animal model experimental autoimmune encephalomyelitis eae represents mslike conditions able measure kinetics partial formation double bilayer systems characterize scattering length density profiles initial final states membrane kinetics modeled using random sequential adsorption simulation using free energy minimization method able calculate shape adhered vesicles determine adhesion energy per mbp native membrane resulting adhesion energy per mbp larger eae modified membrane type observations might help understanding myelination especially remyelinationa process damaged myelin repairedwhich promising candidate treatment still mostly incurable demyelinating diseases mspmid34017815 pmcpmc8129001 doi103389 fchem2021631277,1.0
repurposing domperidone secondary progressive multiple sclerosis simon 2stage phase 2 futility trial neurology 2021 may 4 96 18 e2313e2322 doi 101212 wnl0000000000011863 epub 2021 mar 23abstractobjective assess whether treatment generic drug domperidone can reduce progression disability secondary progressive multiple sclerosis spms conducted phase 2 futility trial following simon 2stage designmethods enrolled patients openlabel simon 2stage singlecenter phase 2 singlearm futility trial calgary multiple sclerosis clinic met following criteria age 18 60 years spms screening expanded disability status scale score 40 65 screening timed 25ft walk t25fw 9 seconds patients received domperidone 10 mg 4 times daily 1 year primary outcome worsening disability defined worsening t25fw performance 20 12 months compared baseline trial registered clinicaltrialsgov nct02308137 results february 13 2015 january 3 2020 110 patients screened 81 received treatment 64 completed followup 62 analyzed study meet primary endpoint 22 62 35 patients experienced significant worsening disability close expected proportion 40 predefined futility threshold patients higher prolactin levels study significantly lower risk disability progression may warrant investigation domperidone treatment reasonably well tolerated adverse events occurred 84 serious adverse events 15 patientsconclusions domperidone treatment reject futility reducing disability progression spms simon 2stage trial model may useful model phase 2 studies progressive mstrial registration information clinicaltrialsgov identifier nct02308137classification evidence study provides class iii evidence individuals spms participating futility trial domperidone treatment reject futility reducing disability progression 12 monthspmid34038379 doi101212 wnl0000000000011863,0.0
new way identify promising therapies progressive multiple sclerosis neurology 2021 may 4 96 18 833834 doi 101212 wnl0000000000011862 epub 2021 mar 23no abstractpmid34038382 doi101212 wnl0000000000011862,1.0
systematic literature review attitudes towards secondary use sharing health administrative clinical trial data focus consent background aimed synthesise data issues related stakeholder perceptions consent use secondary data better understand current literature available conducted systematic literature review healthcare consumer attitudes towards secondary use sharing health administrative clinical trial datamethodsembase medline cochrane library pubmed cinahl informit health collection prospero database systematic reviews psycinfo proquest databases searched eligible articles included reporting qualitative quantitative original research published english restrictions placed publication dates study design disease setting one author screened articles eligibility two authors involved fulltext review process conflicts resolved consensus quality bias assessed using qualsyst criteria qualitative studiesresultsthis paper focuses subset 47 articles identified wider search focuses issue consent issues related privacy trust transparency attitudes healthcare professionals researchers secondary use sharing data dealt previous publications studies included total 216 149 respondents results indicate respondents generally supportive using health data research particularly data deidentified anonymised requirement participants obtain consent prior use health data research universal requirement always supported legislation many respondents believed either consent informed research providing additional consent sufficientconclusionsthese results indicate individuals provided information choice health data used feasible mechanism optout provided increase acceptability using health data research health organisations data custodians must provide individuals concise information data protection mechanisms circumstances data may used whomsystematic review registrationprospero crd42018110559 update june 2020,0.0
repulsive guidance moleculea central nervous system diseases biomed res int 2021 may 4 20215532116 doi 101155 2021 5532116 ecollection 2021abstractrepulsive guidance moleculea rgma member glycosylphosphatidylinositol gpi anchored protein family axon guidance function widely involved development pathological processes central nervous system cns one hand binding rgma receptor neogenin can regulate axonal guidance differentiation neural stem cells neurons survival cells hand rgma can inhibit functional recovery cns inhibiting axonal growth number studies shown rgma may involved pathogenesis cns diseases multiple sclerosis neuromyelitis optica spectrum diseases cerebral infarction spinal cord injury parkinsons disease epilepsy targeting rgma can enhance functional recovery cns may become promising target treatment cns diseases article will comprehensively review research progression rgma various cns diseases datepmid33997000 pmcpmc8112912 doi101155 2021 5532116,0.0
mass cytometry identifies expansion tbet + b cells cd206 + monocytes early multiple sclerosis front immunol 2021 may 4 12653577 doi 103389 fimmu2021653577 ecollection 2021abstractmultiple sclerosis ms immunedriven demyelinating disease central nervous system immune cell features particularly promising predictive biomarkers due central role pathogenesis also drug targets even nowadays impact clinical practice recently highresolution approaches mass cytometry cytof helped better understand diversity functions immune system study performed exploratory analysis blood immune response profiles healthy controls ms patients sampled first neurological relapse using two large cytof panels including 62 markers exploring myeloid lymphoid cells increased abundance tbetexpressing b cell subset cd206+ classical monocyte subset detected blood early ms patients moreover tbetexpressing b cells tended enriched aggressive ms patients study provides new insights understanding pathophysiology ms identification immunological biomarkers studies will required validate results determine exact role identified clusters neuroinflammationpmid34017332 pmcpmc8129576 doi103389 fimmu2021653577,1.0
prevotella histicola protects arthritis expansion allobaculum augmenting butyrate production humanized mice front immunol 2021 may 4 12609644 doi 103389 fimmu2021609644 ecollection 2021abstractbacterial therapeutics emergent alternatives treating autoimmune diseases rheumatoid arthritis ra p histicola mci 001 one therapeutic bacterium proven treat autoimmune diseases ra multiple sclerosis ms animal models present study characterized p histicola mci 001 isolated human duodenal biopsy evaluated impact gut microbial metabolic profile longitudinal study using collageninduced arthritis model hladq8aeo transgenic mice p histicola mci 001 though closely related type strain p histicola dsm 19854 differed utilizing glycerol culture p histicola mci 001 produced vitamins biotin folate involved digesting complex carbohydrates production acetate colonization study showed duodenum predominant niche gavaged mci 001 longitudinal followup gut microbial profile arthritic mice treated mci 001 suggested dysbiosis caused due arthritis partially restored profile nave mice treatment taxonlevel analysis suggested expansion intestinal genus allobaculum mci001 treated arthritic mice eubiosis achieved post treatment p histicola mci 001 also reflected increased production shortchain fatty acids scfas present study suggests treatment p histicola mci 001 leads expansion allobaculum increasing availability simple carbohydrates acetate restoration microbial profile metabolites like butyrate induce immune gut homeostasispmid34017324 pmcpmc8130672 doi103389 fimmu2021609644,0.0
physical exercise improves quality life depressive symptoms cognition across chronic brain disorders transdiagnostic systematic review metaanalysis randomized controlled trialsselect physical exercise improves quality life depressive symptoms cognition across chronic brain disorders transdiagnostic systematic review metaanalysis randomized controlled trialsdauwan m begemann mjh slot mie lee ehm scheltens p sommer iecjournal neurology 2021 apr 268 4 12221246systematic reviewcopyright release abstract granted,0.0
differentiation functions roles t follicular regulatory cells autoimmune diseases abstractt follicular helper cells participate stimulating germinal center gc formation supporting b cell differentiation autoantibody production however t follicular regulatory tfr cells suppress b cell activation since changes number functions tfr cells lead dysregulated gc reaction autoantibody response targeting tfr cells may benefit treatment autoimmune diseases differentiation tfr cells multistage multifactorial process various positive negative regulators therefore understanding signals regulating tfr cell generation crucial development targeted therapies review discuss recent studies elucidated roles tfr cells autoimmune diseases investigated modulators tfr cell differentiation additionally potential immunotherapies targeting tfr cells highlighted,0.0
advancing understanding transportation options auto study design methods multicenter study decision aid older drivers background decisionmaking stop driving older adults involves assessment driving risk availability support resources strong emotions loss independence although risk involved fatal crash increases age driving cessation can negatively impact older adults health wellbeing decision aids can enhance decisionmaking process increasing knowledge risks benefits driving cessation improve decision quality impact decision aids regarding driving cessation older adults unknownmethodsthe advancing understanding transportation options auto study multisite twoarmed randomized controlled trial will test impact decision aid older adults decisions changes driving behaviors cessation auto will enroll 300 drivers age 70 years study partner identified driver dyads will randomized two groups n 150 group decision aid group will view webbased decision aid created healthwise baseline control group will review information driving include evidencebased elements risks benefits values clarification driving decisions auto trial will compare effect decision aid versus control immediate decision quality measured decisional conflict scale primary outcome b longitudinal psychosocial outcomes 12 24 months secondary outcomes c longitudinal driving behaviors including reduction cessation 12 24 months secondary outcomes planned stratified analyses will examine effects subgroups defined cognitive function decisional capacity readiness stop drivingdiscussionthe auto study first largescale randomized trial driving decision aid older adults results study will directly inform clinical practice best support older adults decisionmaking drivingtrial registrationclinicaltrialsgov nct04141891 registered october 28 2019 located https clinicaltrialsgov ct2 show nct04141891,0.0
effect single intraarticular high molecular weight hyaluronan naturally occurring canine osteoarthritis model randomized controlled trial background osteoarthritis oa complex joint disease chronic pain source affecting patients quality life posing financial burden dog considered nearly ideal species translation research human oa used model research exploring spontaneous dog oa one health one medicine concept can improve humans dogs health wellbeingmethodsin clinical treatment experiment forty n40 joints selected randomly assigned control group cg received 09 nacl treatment hg received hylan gf 20 evaluations performed treatment day t0 8 15 30 90 180 days posttreatment consisted four different clinical metrology instruments cmi evaluation weight distribution joint range motion thigh girth radiographic digital thermography imaging synovial fluid interleukin1 il1 creactive protein concentrations results compared repeated measures anova huynhfeldt correction paired samples ttest wilcoxon signedranks test p005resultspatients mean age 6524 years bodyweight 26652kg joints graded mild n28 70 moderate n6 15 severe oa n6 15 differences found groups t0 symmetry index deviation showed significant improvements hg 30 days p001 180 days p001 several cmi scores particularly pain scores improved 90 180 days radiographic signs progressed groups groups increasing body weight age corresponded worse clinical presentation ia hyaluronan administration produced increased lameness six cases resolved spontaneouslyconclusionsthis study characterizes response treatment hylan gf 20 can produce significant functional pain level improvements patients oa even factors related worse response treatment,0.0
association tyk2 polymorphisms autoimmune diseases comprehensive updated systematic review metaanalysis genet mol biol 2021 may 3 44 2 e20200425 doi 101590 16784685gmb20200425 ecollection 2021abstractautoimmune diseases characterized loss selftolerance leading immunemediated tissue destruction chronic inflammation tyrosine kinase 2 tyk2 protein plays key role immunity apoptosis pathways studies reported associations single nucleotide polymorphisms snps tyk2 gene autoimmune diseases however results still inconclusive thus conducted systematic review followed metaanalysis literature search performed find studies investigated associations tyk2 snps autoimmune diseases multiple sclerosis systemic lupus erythematosus crohns disease ulcerative colitis psoriasis rheumatoid arthritis type 1 diabetes inflammatory bowel disease pooled odds ratios 95 ci calculated using random rem fixed fem effects models stata 110 software thirtyfour articles eligible inclusion metaanalyses comprising 9 different snps rs280496 rs280500 rs280523 rs280519 rs2304256 rs12720270 rs12720356 rs34536443 rs35018800 metaanalysis results showed minor alleles rs2304256 rs12720270 rs12720356 rs34536443 rs35018800 snps associated protection autoimmune diseases moreover allele rs280519 snp associated risk systemic lupus erythematosus metaanalyses demonstrated rs2304256 rs12720270 rs12720356 rs34536443 rs35018800 rs280519 snps tyk2 gene associated different autoimmune diseasespmid33949620 doi101590 16784685gmb20200425,0.0
utility delta9tetrahydrocannibinol therapy multiple sclerosis patient neoplastic brain lesion eur j case rep intern med 2021 may 3 8 5 002188 doi 1012890 2021_002188 ecollection 2021abstractmultiple sclerosis ms can sometimes cause uncommon pseudotumoural lesions produce atypical symptoms motor epileptic seizures often pharmacoresistant cases accurate diagnosis essential correct therapy even unconventional present case brain tumour 40yearold relapsingremitting ms patient presented pharmacoresistant seizures eventually responded nabiximols various therapeutic approaches delta9tetrahydrocannabinol therapy introduced good results spasticity improved pain decreased observed reduction number daily seizures possible delta9tetrahydrocannabinol can enhance efficacy antiepilepsy therapylearning points patient experienced fewer daily focal motor crises administration nabiximols morningthe correct combination symptomatic drugs can optimize specific multiple sclerosis ms therapy even real cause symptoms primary brain tumour msthe addition nabiximols therapeutic program allowed antiepilepsy drug doses reduced improved patients cognitive impairmentpmid34123935 pmcpmc8191345 doi1012890 2021_002188,0.0
tumefactive multiple sclerosis versus highgrade glioma diagnostic dilemma surg neurol int 2021 may 3 12199 doi 1025259 sni_901_2020 ecollection 2021abstractbackground tumefactive demyelinating lesions tdls share similar clinical features mri characteristics highgrade glioma hgg study develops approach navigating diagnostic dilemma significant treatment implications management entities drastically differentmethods retrospective analysis 41 tdls 91 hgg respect demographics presentation classical mri characteristics performed diagnostic pathway developed help diagnose tdls based whole neuraxis mri cerebrospinal fluid csf examinationresults diagnosis tdl likely hgg younger females present subacute chronic symptoms mri characteristics favoring tdl hgg include smaller size open rim enhancement little associated edema mass effect presence t2 hypointense rim mri whole neuraxis detection lesions typical multiple sclerosis ms combination lumbar puncture lp showing positive csfspecific oligoclonal bands ocb positive 90 tdl cohortconclusion diagnostic pathway proposed basis specific clinicoradiological features followed patients suspected tdl mri demonstrates lesions typical ms lp demonstrates positive csfspecific ocbs patients undergo short course iv steroids look clinical improvement patients continue deteriorate demonstrate lesions mri lp negative csfspecific ocb considered biopsy safe pathway will give patients best chance neurological preservationpmid34084626 pmcpmc8168700 doi1025259 sni_901_2020,1.0
neuronal metabotropic glutamate receptor 8 protects neurodegeneration cns inflammation j exp med 2021 may 3 218 5 e20201290 doi 101084 jem20201290abstractmultiple sclerosis ms chronic inflammatory disease central nervous system continuous neuronal loss treatment clinical progression remains challenging due lack insights inflammationinduced neurodegenerative pathways show imbalance neuronal receptor interactome driving glutamate excitotoxicity neurons ms patients identify ms riskassociated metabotropic glutamate receptor 8 grm8 decisive modulator mechanistically grm8 activation counteracted neuronal camp accumulation thereby directly desensitizing inositol 1 4 5trisphosphate receptor ip3r profoundly limited glutamateinduced calcium release endoplasmic reticulum subsequent cell death notably found grm8deficient neurons prone glutamate excitotoxicity whereas pharmacological activation grm8 augmented neuroprotection mouse human neurons well preclinical mouse model ms thus demonstrate grm8 conveys neuronal resilience cns inflammation promising neuroprotective target broad therapeutic implicationspmid33661276 doi101084 jem20201290,1.0
therapeutic targeting lyn kinase treat choreaacanthocytosis abstractchoreaacanthocytosis chac devastating little understood currently untreatable neurodegenerative disease caused vps13a mutations based recent demonstration accumulation activated lyn tyrosine kinase key pathophysiological event human chac cells took advantage vps13a mice phenocopied human chac using proteomic approach found accumulation active lyn synuclein phosphotau proteins vps13a basal ganglia secondary impaired autophagy leading neuroinflammation mice double knockout vps13a lyn showed normalization red cell morphology improvement autophagy basal ganglia vivo tested pharmacologic inhibitors lyn dasatinib nilotinib dasatinib failed cross mouse brain blood barrier bbb specific lyn kinase inhibitor nilotinib crosses bbb nilotinib ameliorates vps13a hematological neurological phenotypes improving autophagy preventing neuroinflammation data support proposal repurpose nilotinib new therapeutic option chac patients,0.0
vivo molecular changes retina patients multiple sclerosis invest ophthalmol vis sci 2021 may 3 62 6 11 doi 101167 iovs62611abstractpurpose raman spectroscopy allows molecular changes quantified vivo tissues like retina aimed assess metabolic changes retina patients multiple sclerosis ms methods built raman spectroscopy prototype connecting scanning laser ophthalmoscope spectrophotometer defined spectra 10 molecules participating energy supply axon biology synaptic damage shown altered brain patients ms cytochrome c flavin adenine dinucleotide fad nicotinamide adenine dinucleotide nadh nacetylaspartate naa excitotoxicity glutamate amyloid synuclein snca phosphatidylethanolamine phosphatidylcholine studied molecules prospective cohort patients ms either chronic phase relapses acute optic neuritis aon results significant changes molecules associated age healthy individuals significant decrease nadh trend toward decrease naa patients ms well increase compared healthy controls moreover nadh fad increased time longitudinal analysis patients ms whereas diminished patients acute retinal inflammation due aon significant increase fad decrease snca affected retina moreover glutamate levels increased affected eyes 6month followupconclusions alterations molecules related axonal degeneration observed neuroinflammation show dynamic changes time suggesting progressive neurodegenerationpmid33974046 doi101167 iovs62611,0.0
editorial epidemiology atypical demyelinating diseases front neurol 2021 may 3 12662353 doi 103389 fneur2021662353 ecollection 2021no abstractpmid34012419 pmcpmc8126625 doi103389 fneur2021662353,1.0
physical rehabilitation financing iran policy analysis using kingdons multiple streams background adequate financing crucial function securing physical rehabilitation services ie physiotherapy occupational therapy prosthetics orthotics available financial hardship like many countries despite adoption various policies strategies recent decades iran enjoys desirable physical rehabilitation financing prf accordingly qualitative study aimed explore prfrelated strategies issues well impacts relevant policies iranmethodsan analysis prfrelated policies conducted iran using semistructured interviews policy documents review purposive snowball sampling techniques employed select key informants including healthpolicy makers civil society rehabilitationpolicy makers university professors practitioners thematic analysis used analyze collected data analysis framed within kingdons multiple streamsresultsthe hindering factors desirable financing weak insurance coverage lack sustainable financial resources fragmented financing lack split provider financer highcost physical rehabilitation services low engagement relevant experts policymaking processes corrupt activities policy stream following factors highlighted involvement sustainable financial resources use external revenue sources allocated resources earmarking integration current funds better pooling use incentive timely payment mechanisms implementation strategic purchasing principals employment effective rationing strategies moreover parliament support changes administrations international effects pressures interest campaigns ngos international sanctions found factors affecting politics streamconclusionthe study findings revealed variety national international factors affect prfrelated issues iran recently enacted laws indicate prf policies already national health political agenda study reflected multifaceted nature barriers optimal prf iran,0.0
longitudinal study retinal structure vascular neuronal function patients relapsingremitting multiple sclerosis 1year followup transl vis sci technol 2021 may 3 10 6 6 doi 101167 tvst1066abstractobjective purpose study quantify retinal structural vascular functional changes patients relapsingremitting multiple sclerosis rrms 1 yearmethods eightyeight eyes 44 patients rrms underwent assessments low contrast letter acuity lcla retinal ganglion cell function detected steadystate pattern electroretinogram perg axonal microstructural integrity measured birefringence intraretinal layer thicknesses ultrahighresolution optical coherence tomography oct volumetric vessel density vvd oct angiography retinal tissue perfusion rtp retinal function imager rfi measurements performed baseline 1year followup impacts disease activities history optic neuritis analyzedresults compared baseline significant differences variables p 005 except axonal birefringence rtp birefringences retinal fiber layer temporal superior quadrants significantly decreased p 005 whereas rtp significantly increased p 005 subgroup significantly longer perg latency decreased vvd observed followup p 005 patients improved lcla significantly increased rtp decreased vvd p 005 also observedconclusions first longitudinal study assessed rtp vvd along retinal structural functional parameters ms recovery retinal vascular function occurred improved lcla suggesting measurements may associated disease progressiontranslational relevance retinal microvascular changes potential biomarkers monitoring therapeutic efficacy mspmid34111252 doi101167 tvst1066,0.0
clozapine regulates microglia effective chronic experimental autoimmune encephalomyelitis front immunol 2021 may 3 12656941 doi 103389 fimmu2021656941 ecollection 2021abstractobjective progressive multiple sclerosis characterized chronic inflammation microglial activation oxidative stress accumulation iron continuous neurodegeneration inadequate effectiveness medications used far now investigated effects iron microglia used previously identified neuroprotective antipsychotic clozapine vitro chronic experimental autoimmune encephalomyelitis eae methods microglia treated iron clozapine followed analysis cell death response oxidative stress cytokine release neuronal phagocytosis clozapine investigated chronic eae regarding optimal dosing therapeutic effectiveness different treatment paradigms animals scored clinically blinded raters spinal cords analyzed histologically inflammation demyelination microglial activation iron accumulation transcription changes regulators iron metabolism inflammation effects immune cells analyzed using flow cytometryresults iron impaired microglial function vitro regarding phagocytosis markers inflammation regulated clozapine reflected reduced release il6 normalization neuronal phagocytosis chronic eae clozapine dosedependently attenuated clinical signs still effect applied therapeutic setting early mild sedative effects habituated time histologically demyelination reduced clozapine positive effects inflammation strongly correlated reduced iron deposition accompanied reduced expression dmt1 iron transport proteinconclusions clozapine regulates microglial function attenuates chronic eae even therapeutic treatment paradigm welldefined generic medication might therefore considered promising addon therapeutic development progressive mspmid34012440 pmcpmc8126707 doi103389 fimmu2021656941,1.0
digital twins multiple sclerosis front immunol 2021 may 3 12669811 doi 103389 fimmu2021669811 ecollection 2021abstractan individualized innovative disease management great importance people multiple sclerosis pwms cope complexity chronic multidimensional disease however individual state art strategy precise adjustment patients characteristics still far part everyday care pwms development digital twins decisively advance necessary implementation individualized innovative management ms artificial intelligencebased analysis several disease parameters including clinical paraclinical outcomes multiomics biomarkers patientrelated data information patients life circumstances plans medical procedures digital twin paired patients characteristic can created enabling healthcare professionals handle large amounts patient data can contribute personalized effective care integrating data multiple sources standardized manner implementing individualized clinical pathways supporting physicianpatient communication facilitating shared decisionmaking clear display preanalyzed patient data dashboard patient participation individualized clinical decisions well prediction disease progression treatment simulation become possible review focus advantages challenges practical aspects digital twins management ms discuss use digital twins ms revolutionary tool improve diagnosis monitoring therapy refining patients wellbeing saving economic costs enabling prevention disease progression digital twins will help make precision medicine patientcentered care reality everyday lifepmid34012452 pmcpmc8128142 doi103389 fimmu2021669811,0.0
false positive results sarscov2 serological tests samples patients chronic inflammatory diseases front immunol 2021 may 3 12666114 doi 103389 fimmu2021666114 ecollection 2021abstractpatients chronic inflammatory diseases often treated immunosuppressants therefore particular concern sarscov2 pandemic serological tests will improve understanding infection immunity population unless tests give false positive results aim study evaluate specificity sarscov2 serological assays using samples patients chronic inflammatory diseases collected prior april 2019 thus defined negative samples patients multiple sclerosis ms n10 rheumatoid arthritis ra n47 without rheumatoid factor rf anticyclic citrullinated peptide antibodies anticcp2 systemic lupus erythematosus sle n10 without rf analyzed sarscov2 antibodies using 17 commercially available lateral flow assays lfa two elisa kits one inhouse developed igg multiplex beadbased assay six lfa inhouse validated igg assay correctly produced negative results samples however majority assays n13 gave false positive signal samples patients ra sle notable samples rf positive ra patients false positive samples detected assay using samples patients ms poor specificity commercial serological assays possibly least partly due interfering antibodies samples patients chronic inflammatory diseases patients risk false positivity considered interpreting results sarscov2 serological assayspmid34012450 pmcpmc8126683 doi103389 fimmu2021666114,0.0
correlation osteoarthritis atlantoaxial facet joint highriding vertebral artery background highriding vertebral artery hrva intraosseous anomaly narrows trajectory c2 pedicle screws prevalence hrva high patients need surgery craniovertebral junction reports hrvas subaxial cervical spine disorders limited sought determine prevalence hrvas among patients subaxial cervical spine disorders elucidate potential risk va injury subaxial cervical spine surgerymethodswe included 215 patients 94 main lesion c3 c7 subaxial group 121 main lesion t1 l5 thoracolumbar group hrva defined maximum c2 pedicle diameter 35 mm axial ct sex age patients body mass index bmi osteoarthritis atlantoaxial c12 facet joints prevalence hrva 2 groups compared logistic regression used identify factors correlated hrvaresultsthe patients subaxial group younger thoracolumbar group sex bmi differ significantly 2 groups mean osteoarthritis grade c12 facet joints patients subaxial group significantly higher thoracolumbar group hrva found 26 patients 94 277 subaxial group 19 121 157 thoracolumbar group prevalence hrva subaxial group significantly higher osteoarthritis c12 facet joints correlated significantly hrvaconclusionsthe prevalence hrva patients subaxial cervical spine disorders higher without osteoarthritis c12 facet joints correlated hrva,0.0
soluble guanylate cyclase stimulator reduced gastrointestinal fibrosis bleomycininduced mouse model systemic sclerosis background systemic sclerosis ssc chronic autoimmunemediated connective tissue disorder although etiology disease remains undetermined ssc characterized fibrosis proliferative vascular lesions skin internal organs ssc involves gastrointestinal tract 90 patients soluble guanylate cyclase sgc stimulator used treat pulmonary artery hypertension pah shown inhibit experimental skin fibrosismethodsfemale c57bl 6j mice treated blm normal saline subcutaneous implantation osmotic minipump mice sacrificed day 28 day 42 gastrointestinal pathologies examined masson trichrome staining expression fibrosisrelated genes gastrointestinal tract analyzed realtime pcr levels collagen tissue measured sircol collagen assay evaluate peristaltic movement small intestinal transport itr calculated dyeing distance duodenum appendix 1 100 treated blmtreated mice sgc stimulator dmso orally analyzed day 42resultshistological examination revealed fibrosis lamina propria muscularis mucosa esophagus significantly increased blmtreated mice suggesting blm induces esophageal hyperproliferative prefibrotic response c57bl 6j mice addition gene expression levels col3a1 ccn2 mmp2 mmp9 timp1 timp2 esophagus significantly increased blmtreated mice severe hyperproliferative prefibrotic response observed mice sacrificed day 42 mice sacrificed day 28 itr found significantly lower blmtreated mice suggesting gastrointestinal peristaltic movement reduced blmtreated mice furthermore demonstrated sgc stimulator treatment significantly reduced hyperproliferative prefibrotic response esophagus intestine blmtreated mice histological examination sircol collagen assayconclusionsthese findings suggest blm induces gastrointestinal hyperproliferative prefibrotic response c57bl 6j mice treatment sgc stimulator improves blminduced gastrointestinal lesion,0.0
role diseasemodifying oral drugs multiple sclerosis systematic review metaanalysis abstractthe purpose study evaluate efficacy safety cladribine tablets compared oral therapies used patients relapsingremitting multiple sclerosis rrms systematic review literature conducted identify published clinical trials rrms network metaanalysis performed determine efficacy safety available treatments identified seven relevant studies selected based three criteria allowed us construct comparisons efficacy safety regarding annualized relapse rate arr significant differences respect decrease cladribine tablets dimethyl fumarate fingolimod although teriflunomide cladribine tablets showed significant difference relation mean number gadoliniumenhanced t1 lesions dimethyl fumarate showed lower number lesions 085 121 048 cladribine tablets versus placebo statistically significant differences identified cladribine tablets fingolimod 008 035 019 cladribine versus teriflunomide 028 064 008 comparing adverse events caused discontinuation cladribine tablets showed adequate safety profile quantitatively similar compared drugs cladribine tablets demonstrated efficacy terms decrease arr gadoliniumenhanced t1 lesions although significant difference cladribine tablets fingolimod teriflunomide arr stronger measure efficacy compared number t1 lesions made contrast longterm rrms cladribine also demonstrated adequate safety tolerability profile promoting therapeutic adherence,0.0
lrrc4 functions neuronprotective role experimental autoimmune encephalomyelitis background leucine rich repeat containing 4 lrrc4 also known netring ligand2 ngl2 belongs superfamily lrr proteins serves receptor netring2 lrrc4 regulates formation excitatory synapses promotes axon differentiation mutations lrrc4 occur autism spectrum disorder asd intellectual disability multiple sclerosis ms chronic neuroinflammatory disease spinal cords demyelination neurodegeneration sought investigate whether lrrc4 involved spinal cords neuronassociated diseasesmethodslrrc4 detected cns experimental autoimmune encephalomyelitis eae mice use realtime pcr western blotting lrrc4 mice created immunized myelin oligodendrocyte glycoprotein peptide mog 3555 pathological changes spinal cords lrrc4 wt mice 15 days immunization examined using hematoxylin eosin luxol fast blue lfb staining immunohistochemistry number th1 th2 th17 treg cells spleens blood measured flow cytometry differential gene expression spinal cords wt lrrc4 mice analyzed using rna sequencing rnaseq adenoassociated virus aav vectors used overexpress lrrc4 aavlrrc4 injected eae mice assess therapeutic effect aavlrrc4 ectopic expression eaeresultswe report lrrc4 mainly expressed neuron spinal cords decreased spinal cords eae mice knockout lrrc4 disease progression quickened exacerbated severe myelin degeneration infiltration leukocytes spinal cords also first found rab7b high expressed eae mice deficiency lrrc4 induces elevated nfb p65 upregulating rab7b upregulation il6 ifn downregulation tnf results severe th1 immune response lrrc4 mice ectopic expression lrrc4 alleviates clinical symptoms eae mice protects neurons immune damagesconclusionswe identified neuroprotective role lrrc4 progression eae may used potential target auxiliary support therapeutic treatment ms,1.0
serum proteomic profiling patients advanced schistosoma japonicuminduced hepatic fibrosis background schistosoma japonicum parasitic flatworm aetiological agent human schistosomiasis important cause hepatic fibrosis schistosomiasisinduced hepatic fibrosis consequence highly fibrogenic nature egginduced granulomatous lesions main pathogenic features schistosomiasis although global awareness association schistosomiasisinduced hepatic fibrosis s japonicum infection increasing little known molecular differences associated rapid progression schistosomiasis cirrhotic patientsmethodswe systematically used dataindependent acquisition dia based liquid chromatographymass spectrometry identify differentially expressed proteins serum samples patients advanced s japonicuminduced hepatic fibrosisresultsour analysis identified 1144 proteins among 66 differentially expressed healthy control group group patients advanced s japonicuminduced hepatic fibrosis stage f2 shff2 214 differentially expressed shff2 shff4 groups downregulation least 15fold serum samples results also indicated two selected proteins c1qa cfd potential biomarkers distinguishing patients shff2 shff4 due s japonicum infectionconclusionswe provide first global proteomic profile serum samples patients advanced s japonicuminduced hepatic fibrosis proteins c1qa cfd potential diagnostic markers patients shff2 shff4 due s japonicum infection although largescale studies needed diabased quantitative proteomic analysis revealed molecular differences among individuals different stages advanced s japonicuminduced hepatic fibrosis may provide fundamental information detailed investigationsgraphical abstract,0.0
multimodal evoked potentials candidate prognostic response biomarkers clinical trials multiple sclerosis j clin neurophysiol 2021 may 1 38 3 171180 doi 101097 wnp0000000000000723abstractevoked potentials eps measure quantitatively objectively alterations central signal propagation multiple sclerosis long used diagnosis recently utility prognosis demonstrated several studies summarizing multiple ep modalities single score particular visual somatosensory motor eps useful sensitivity pathology frequently affected optic nerve somatosensory tract pyramidal system quantitative ep scores show higher sensitivity change clinical assessment may used monitor disease progression visual ep visual system served model study remyelinating therapies setting acute chronic optic neuritis review presents rationale evidence using multimodal ep prognostic response biomarkers clinical trials targeting remyelination halting disease progression multiple sclerosispmid33958567 doi101097 wnp0000000000000723,1.0
intradatabase validation caseidentifying algorithms using reconstituted electronic health records healthcare claims data background diagnosis performances caseidentifying algorithms developed healthcare database usually assessed comparing identified cases external data source feasible intradatabase validation can present appropriate alternativeobjectivesto illustrate two practical examples perform intradatabase validations caseidentifying algorithms using reconstituted electronic health records rehrs methodspatients 1 multiple sclerosis ms relapses 2 metastatic castrationresistant prostate cancer mcrpc identified french nationwide healthcare database snds using two caseidentifying algorithms validation study conducted estimate diagnostic performances algorithms calculation positive predictive value ppv negative predictive value npv end anonymized rehrs generated based overall information captured snds time eg procedure hospital stays drug dispensing medical visits random selection patients identified cases noncases according predefined algorithms disease independent validation committee reviewed rehrs 100 cases 100 noncases order adjudicate status selected patients true case true noncase blinded respect result corresponding algorithmresultsalgorithm relapses identification ms showed 95 ppv 100 npv algorithm mcrpc identification showed 97 ppv 99 npvconclusionthe use rehrs conduct intradatabase validation appears valuable tool estimate performances caseidentifying algorithm assess validity absence alternative,0.0
rituximab risk covid19 infection severity patients ms nmosd background choosing safe disease modifying therapy covid19 pandemic challenging case series study conducted determine incidence rate course covid19 infection ms nmosd patients treated rituximabmethodsin study designed webbased questionnaire baseline information patient reported walking disability total number rituximab infusions received delayed injections occurrence relapse use corticosteroids pandemic collected also information regarding covid19 pandemic adherence selfisolation recent exposure infected individual presence suggestive symptoms collected case positive test results patients grouped 2 categories mild moderate seriously ill outcomes evaluated favorable improved discharged unfavorable expired resultstwo hundred fiftyeight patients multiple sclerosis enrolled study 9 subjects 34 confirmed positive covid19 five required hospitalizations 555 two patients required icu admission 222 2 two patients died 222 none patients ever mentioned using corticosteroids pandemic comparison ms patients receiving disease modifying therapy dmt study indicated higher incidence covid19 infection higher ratio serious illness higher fatality ratioconclusionsrituximab seems safe enough pandemic,0.0
evidence grn connecting multiple neurodegenerative diseases brain commun 2021 may 1 3 2 fcab095 doi 101093 braincomms fcab095 ecollection 2021abstractprevious research using genomewide association studies identified variants may contribute lifetime risk multiple neurodegenerative diseases however whether common mechanisms link neurodegenerative diseases uncertain focus one gene grn encoding progranulin potential mechanistic interplay genetic risk gene expression brain inflammation across multiple common neurodegenerative diseases utilized genomewide association studies expression quantitative trait locus mapping bayesian colocalization analyses evaluate potential causal mechanistic inferences integrate various molecular data types public resources infer disease connectivity shared mechanisms using datadriven process expression quantitative trait locus analyses combined genomewide association studies identified significant functional associations increasing genetic risk grn region decreased expression gene parkinsons alzheimers amyotrophic lateral sclerosis additionally colocalization analyses show connection bloodbased inflammatory biomarkers relating platelets grn expression frontal cortex grn expression mediates neuroinflammation function related multiple neurodegenerative diseases analysis suggests shared mechanisms parkinsons alzheimers amyotrophic lateral sclerosispmid34693284 pmcpmc8134835 doi101093 braincomms fcab095,0.0
sting agonist mitigates experimental autoimmune encephalomyelitis stimulating type ifndependent independent immuneregulatory pathways j immunol 2021 apr 5ji2001317 doi 104049 jimmunol2001317 online ahead printabstractthe cgascyclic gmpamp cgamp stimulator ifn genes sting pathway induces powerful type ifn ifni response prime candidate augmenting immunity cancer immunotherapy vaccines ifni also immuneregulatory functions manifested several autoimmune diseases firstline therapy relapsingremitting multiple sclerosis however moderately effective can induce adverse effects neutralizing abs recipients targeting cgamp autoimmunity unexplored represents challenge intracellular location receptor sting used microparticle mp encapsulated cgamp increase cellular delivery achieve dose sparing reduce potential toxicity c57bl 6 experimental allergic encephalomyelitis eae model cgamp encapsulated mps cgamp mps administered therapeutically protected mice eae stingdependent fashion whereas soluble cgamp ineffective protection also observed relapsingremitting model importantly cgamp mps protected eae peak disease effective rifn mechanistically cgamp mps showed ifnidependent independent immunosuppressive effects furthermore induced immunosuppressive cytokine il27 without requiring ifni augmented il10 expression activated erk creb il27 subsequent il10 important cytokines mitigate autoreactivity critically cgamp mps promoted ifni well immunoregulatory cytokines il27 il10 pbmcs relapsingremitting multiple sclerosis patients collectively study reveals previously unappreciated immuneregulatory effect cgamp can harnessed restrain t cell autoreactivitypmid33820855 doi104049 jimmunol2001317,0.0
serum gfap nfl disease severity prognostic biomarkers patients aquaporin4 antibodypositive neuromyelitis optica spectrum disorder background neuromyelitis optica spectrum disorder nmosd frequently disabling neuroinflammatory syndrome relapsing course bloodbased disease severity prognostic biomarkers nmosd yet unmet clinical need evaluated serum glial fibrillary acidic protein sgfap neurofilament light snfl disease severity prognostic biomarkers patients aquaporin4 immunoglobulin ig g positive aqp4igg+ nmosdmethodssgfap snfl determined singlemolecule array technology prospective cohort 33 aqp4igg+ patients nmosd 32 clinical remission study baseline sixteen myelin oligodendrocyte glycoprotein iggpositive mogigg+ patients 38 healthy persons included controls attacks recorded aqp4igg+ patients median observation period 425 yearsresultsin patients aqp4igg+ nmosd median sgfap 1092 pg ml nonsignificantly higher mogigg+ patients 811 pg ml p 083 healthy controls 677 pg ml p 007 snfl substantially differ groups yet aqp4igg+ mogigg+ patients higher sgfap associated worse clinical disability scores including expanded disability status scale edss standardized effect size 130 p 0007 multiple sclerosis functional composite msfc standardized effect size 128 p 001 aqp4igg+ mogigg+ patients baseline sgfap snfl positively associated standardized effect size 224 p 0001 higher snfl nonsignificantly associated worse edss standardized effect size 109 p 015 msfc standardized effect size 175 p 006 patients aqp4igg+ nmosd patients aqp4igg+ nmosd sgfap 90 pg ml baseline shorter time future attack sgfap 90 pg ml adjusted hazard ratio 95 confidence interval 116 131056 p 003 contrast baseline snfl levels 75th age adjusted percentile associated shorter time future attack patients aqp4igg+ nmosdconclusionthese findings suggest potential role sgfap biomarker disease severity future disease activity patients aqp4igg+ nmosd phases clinical remission,1.0
changing paradigms unmet needs multiple sclerosis role clinical neurophysiology j clin neurophysiol 2021 may 1 38 3 162165 doi 101097 wnp0000000000000749abstractour increasing understanding immunopathogenesis multiple sclerosis led development many diseasemodifying therapies revolutionized care patients relapsing forms disease understanding pathophysiologic basis progressive forms disease much limited dramatically changed past several decades now verge developing therapies promote remyelination reduce axonal loss restore axonal function progress challenged inadequate animal models progressive disease incomplete biomarkers progression measuring central nervous system function evoked potentials may advantage biomarkers measure pathologic change monitoring multifocal visual evoked potential amplitude may one possible means monitoring disease progression multiple sclerosis additional clinical studies required document whether evoked potentials can adequately serve effective biomarkers progressionpmid33958565 doi101097 wnp0000000000000749,1.0
biomarkers surrogate end points multiple sclerosis trials regulatory issues j clin neurophysiol 2021 may 1 38 3 181185 doi 101097 wnp0000000000000732abstractevoked potentials assisted diagnosis multiple sclerosis years potential demonstrate pathophysiologic change prompted reconsideration potential role outcome measures clinical trials multiple sclerosis use surrogate end point biomarker clinical trials requires thorough understanding end points performance characteristics utility particular setting article explores regulatory issues regarding use biomarkers surrogate end points clinical trials multiple sclerosis particular emphasis challenges faced evoked potential studiespmid33958568 doi101097 wnp0000000000000732,0.0
clinical characteristics 40 patients longitudinally extensive transverse myelitis connective tissue disease zhonghua nei ke za zhi 2021 may 1 60 5 453458 doi 103760 cmajcn1121382021010400004abstractobjective longitudinally extensive transverse myelitis letm seen patients connective tissue disease ctd especially systemic lupus erythematosus sle primary sjgrens syndrome pss patients combined neuromyelitis optica spectrum disorders nmosd termed ctdletmnmosd others without termed ctdletmnonnmosd aim study compare clinical characteristics ctdletmnmosd patients ctdletmnonnmosd patients methods retrospectively collected data 40 ctd patients letm admitted department neurology rheumatology peking union medical college hospital jan 2006 dec 2016 divided ctdletmnmosd ctdletmnonnmosd two groups demographic characteristics clinical laboratory features obtained database relapse rates clinical outcome analyzed kaplanmeier method results among 40 patients ctd 28 700 nmosd 12 300 positivity rates antissa antibodies aquaporin4 antiaqp4 significantly higher patients nmosd patients nonnmosd p005 age gender clinical features disease duration antidoublestranded dna antibody antiribosomal p antibody antiphospholipid antibodies expanded disability status scale edss scores magnetic resonance imaging mri features comparable two groups ctdnmosd patients significantly higher disease relapse rate 750 vs 3 12 p001 conclusion antissa antiaqp4 positivity associated nmosd higher relapse rates suggests nmosd ctdletm patients may represent distinct characteristics pathogenesis patients ctdletmnon nmosdpmid33906275 doi103760 cmajcn1121382021010400004,0.0
use motorevoked potentials clinical trials multiple sclerosis j clin neurophysiol 2021 may 1 38 3 166170 doi 101097 wnp0000000000000734abstractmotorevoked potentials meps can used assess integrity descending corticospinal tract laboratory evoked potentials eps widely used past diagnosis multiple sclerosis ms now becoming useful assessing prognosis disease motorevoked potentials included ep scales demonstrated good correlations clinical disability soon onset ms possible detect ongoing process neurodegeneration axonal loss axonal loss probably responsible disability disease progression occurs ms given good correlations eps detecting disease progression ms used monitor effects drugs used treat disease several clinical trials used meps part ep evaluation meps never used measure efficacy clinical trials testing neuroprotective agents although meps promising tool measure neuroprotection remyelination resulting drugs used multicenter clinical trials mep readings comparable centers standardized multicenter ep assessment central reading demonstrated feasible reliable although mep measurements correlated clinical scores measures neurodegeneration validation mep amplitude measurements needed regarding validity reliability sensitivity can routinely used clinical drug trials mspmid33958566 doi101097 wnp0000000000000734,1.0
conditional deletions hdc confirm roles histamine anaphylaxis circadian activity autoimmune encephalomyelitis j immunol 2021 apr 12ji2000719 doi 104049 jimmunol2000719 online ahead printabstracthistamine best known role allergies also involved autoimmune diseases multiple sclerosis however studies using experimental autoimmune encephalomyelitis eae widely used animal model multiple sclerosis reported conflicting observations suggest implication nonclassical source histamine study demonstrate neutrophils main producers histamine spinal cord eae mice assess role histamine taking account different cellular sources used crisprcas9 generate conditional knockout mice histaminesynthesizing enzyme histidine decarboxylase found ubiquitous cellspecific deletions affect course eae however neutrophilspecific deletion attenuates hypothermia caused igemediated anaphylaxis whereas neuronspecific deletion reduces circadian activity summary study refutes role histamine eae unveils role neutrophilderived histamine igemediated anaphylaxis establishes new mouse model reexplore inflammatory neurologic roles histaminepmid33846226 doi104049 jimmunol2000719,0.0
ponesimod compared teriflunomide patients relapsing multiple sclerosis activecomparator phase 3 optimum study randomized clinical trial jama neurol 2021 mar 29 doi 101001 jamaneurol20210405 online ahead printabstractimportance knowledge oral ponesimod versus teriflunomide relapsing multiple sclerosis optimum trial first phase 3 study comparing 2 oral diseasemodifying therapies relapsing multiple sclerosis rms objective compare efficacy ponesimod selective sphingosine1phosphate receptor 1 s1p1 modulator teriflunomide pyrimidine synthesis inhibitor approved treatment patients rmsdesign setting participants multicenter doubleblind activecomparator superiority randomized clinical trial enrolled patients april 27 2015 may 16 2019 aged 18 55 years diagnosed multiple sclerosis per 2010 mcdonald criteria relapsing course onset expanded disability status scale edss scores 0 55 recent clinical magnetic resonance imaging disease activityinterventions patients randomized 11 20 mg ponesimod 14 mg teriflunomide daily placebo 108 weeks 14day gradual uptitration ponesimod starting 2 mg mitigate firstdose cardiac effects s1p1 modulators followup period 30 daysmain outcomes measures primary end point annualized relapse rate secondary end points changes symptom domain fatigue symptom impact questionnairerelapsing multiple sclerosis fsiqrms week 108 number combined unique active lesions per year magnetic resonance imaging time 12week 24week confirmed disability accumulation safety tolerability assessed exploratory end points included percentage change brain volume evidence disease activity neda3 neda4 statusresults 1133 patients 567 receiving ponesimod 566 receiving teriflunomide median range 370 1855 years 735 women 649 relative rate reduction ponesimod vs teriflunomide annualized relapse rate 305 0202 vs 0290 p 001 mean difference fsiqrms 357 001 vs 356 p 001 relative risk reduction combined unique active lesions per year 56 1405 vs 3164 p 001 reduction time 12week 24week confirmed disability accumulation risk estimates 17 101 vs 124 p 29 16 81 vs 99 p 37 respectively brain volume loss week 108 lower 034 091 vs 125 p 001 odds ratio neda3 achievement 170 250 vs 164 p 001 incidence treatmentemergent adverse events 502 565 888 vs 499 566 882 serious treatmentemergent adverse events 49 87 vs 46 81 similar groups treatment discontinuations adverse events common ponesimod group 49 565 87 vs 34 566 60 conclusions relevance study ponesimod superior teriflunomide annualized relapse rate reduction fatigue magnetic resonance imaging activity brain volume loss evidence disease activity status confirmed disability accumulation safety profile line previous safety observations ponesimod known profile s1p receptor modulatorstrial registration clinicaltrialsgov identifier nct02425644pmid33779698 doi101001 jamaneurol20210405,0.0
proteome study cutaneous lupus erythematosus cle dermatomyositis skin lesions reveals il16 differentially upregulated cle background objective study explore disease pathways activated inflammatory foci skin lesions cutaneous lupus erythematosus cle dermatomyositis dm methodsskin biopsies acquired active cle dm lesions patient pc also healthy controls hc investigated biopsy sections examined pathologist inflammatory foci laser microdissected captured proteins within captured tissue detected unbiased manner mass spectrometry protein pathway analysis performed stringdborg platform findings interest confirmed immunohistochemistry ihc resultsproteome investigation identified abundant expression interferonregulated proteins irp common feature cle dm interleukin il 16 abundant cytokine differentially expressed cle compared dm caspase3 enzyme cleaves il16 active form detected low levels significantly higher proportion il16 caspase3positive cells identified cle lesions comparison dm pc hc proteomic results indicate abundant complement deposition cle skin lesionsconclusionsusing unbiased mass spectrometry investigation cle dm inflammatory infiltrates confirmed high irp expression common feature cle dm il16 differentially expressed cytokine cle ihc confirmed high expression il16 caspase3 cle novel molecular findings indicate il16 detection useful differential diagnostics two conditions can display similar histopathological appearance il16 interest future therapeutic target cle,0.0
association mental health caries experience gingival health adolescents suburban nigeria background study assessed association mental health problems risk indicators mental health problems caries experience moderate severe gingivitis adolescentsmethodsa crosssectional household survey conducted osun state nigeria data collected 10 19yearsold adolescents december 2018 january 2019 sociodemographic variables age sex socioeconomic status oral health indicators tooth brushing use fluoridated toothpaste consumption refined carbohydrates inbetweenmeals dental services utilization dental anxiety plaque mental health indicators smoking habits intake alcohol use psychoactive drugs mental health problems low high gingival health healthy gingiva mild gingivitis versus moderate severe gingivitis caries experience present absent also assessed series five logistic regression models constructed determine association presence caries experience presence moderate severe gingivitis blocks independent variables blocks model 1sociodemographic factors model 2oral health indicators model 3mental health indicators model 4mental health problems model 5 included factors models 1 4resultsthere 1234 adolescents mean sd age 146 27 years also 211 participants high risk mental health problems 37 caries experience 81 moderate severe gingivitis model 5 best fit two dependent variables use psychoactive substances aor 267 95 ci 114 626 associated significantly higher odds caries experience frequent consumption refined carbohydrates inbetweenmeals aor 041 95 ci 025 066 severe dental anxiety aor048 95 ci 023 099 associated significantly lower odds moderate severe gingivitis plaque associated significant higher odds moderate severe gingivitis aor 1350 95 ci 866 2104 high risk mental health problems significantly associated caries experience aor 184 95 ci 097 349 moderate severe gingivitis aor 080 95 ci 045 144 conclusionthe association mental problems risk indicators oral diseases nigerian adolescents indicates need integrated mental oral health care improve wellbeing adolescents,0.0
optimising psychological treatment anxiety disorders pregnancy adept study protocol feasibility trial timeintensive cbt versus weekly cbt background moderate severe anxiety disorders obsessivecompulsive disorder ocd posttraumatic stress disorder ptsd social phobia panic disorder common affect approximately 1116 women pregnancy psychological treatments anxiety disorders primarily cognitive behaviour therapy cbt substantial evidence base recently timeintensive versions found effective weekly treatments however trialled women pregnant shorter intervention may desirablemethodsthe adept study feasibility randomised controlled trial two parallel intervention groups timeintensive onetoone cbt standard weekly onetoone cbt delivered pregnancy will compared feasibility outcomes including participation followup rates will assessed alongside acceptability interventions using qualitative methodsdiscussionthe study will provide preliminary data inform design fullscale randomised controlled trial timeintensive intervention anxiety pregnancy will include information acceptability timeintensive interventions pregnant women anxiety disorderstrial registrationhttps doiorg 101186 isrctn81203286 prospectively registered 27 6 2019,0.0
hypokalaemic paralysis metabolic alkalosis patient sjgren syndrome case report literature review background acquired gitelman syndrome rare disorder reported association autoimmune disorders mostly sjgren syndrome characterized presence hypokalaemic metabolic alkalosis hypocalciuria hypomagnesaemia hyperreninaemia absence typical genetic mutations associated inherited gitelman syndromecase presentationa 20 year old woman previously diagnosed primary sjgren syndrome autoimmune thyroiditis presented two week history lower limb weakness salt craving examination revealed upper limb lower limb muscle weakness muscle power 3 5 mrc scale diminished deep tendon reflexes evaluation hypokalaemia high transtubular potassium gradient metabolic alkalosis hypocalciuria features suggestive gitelman syndrome new onset hypokalaemic alkalosis previously normokalaemic patient sjgren syndrome strongly favored diagnosis acquired gitelman syndrome daily potassium supplementation spironolactone resulted complete clinical recoveryconclusionsacquired gitelman syndrome associated sjgren syndrome rare considered differential diagnosis evaluation acute paralysis hypokalaemic metabolic alkalosis patients autoimmune disorders especially sjgren syndrome,0.0
risk progressive multifocal leukoencephalopathy multiple sclerosis patient treated natalizumab systematic review cureus 2021 apr 30 13 4 e14764 doi 107759 cureus14764abstractnatalizumab monoclonal antibody acting alpha4 integrin receptors frequently used treat multiple sclerosis patients biggest downside risk development progressive multifocal leukoencephalopathy immunerelated condition affecting mainly central nervous system presence john cunningham virus jcv reactivation important factor development progressive multifocal leukoencephalopathy pml study highlights different proposed mechanism risk factors strongly related natalizumabinduced progressive multifocal leukoencephalopathy pieces literature will also reviewed look relation jcv natalizumabinduced progressive multifocal leukoencephalopathy multiple sclerosis treated patients articles searched three databases reviewed systematically inclusion criteria study patients aged 2050 years english language paper fulltext availability human studies whereas articles patients aids cancerrelated disease prior natalizumab treatment excluded 6531 articles identified applying search strategy three main databases pubmed google scholar researchgate total 32 articles finalized review study follows guidelines listed preferred reporting items systematic reviews metaanalyses prisma checklist 2009 data collected finalized articles pertaining risk factor related natalizumab induced progressive multifocal leukoencephalopathy mechanism related pathogenesis natalizumab known potential cause progressive multifocal leukoencephalopathy treated patients evaluate close relationship related risk factors articles studied exhibit close relationship length natalizumab treatment presence jcv infusion natalizumab analysis seems mechanism related natalizumabinduced pml strongly related antigenspecific t cells effects frequency monitoring vigilance management patients treated natalizumab will help detect progressive multifocal leukoencephalopathypmid34094729 pmcpmc8169000 doi107759 cureus14764,0.0
genetic impacts dna methylation research findings future perspectives abstractmultiple recent studies highlight genetic variants can strong impacts significant proportion human dna methylome methylation quantitative trait loci meqtls allow exploration biological mechanisms underlie complex human phenotypes potential insights human disease onset progression review summarize recent milestones characterizing human genetic basis dna methylation variation last decade including heritability findings genomewide identification meqtls also discuss challenges field future areas research geared generate insights molecular processes underlying human complex traits,0.0
mars leveraging allelic heterogeneity increase power association testing abstractin standard genomewide association studies gwas standard association test underpowered detect associations loci multiple causal variants small effect sizes propose statistical method modelbased association test reflecting causal status mars finds associations variants risk loci phenotype considering causal status variants requiring existing summary statistics detect associated risk loci utilizing extensive simulated data real data show mars increases power detecting true associated risk loci compared previous approaches consider multiple variants controlling type error,0.0
novel insight role immune dysregulation amyotrophic lateral sclerosis based bioinformatic analysis front neurosci 2021 apr 30 15657465 doi 103389 fnins2021657465 ecollection 2021abstractamyotrophic lateral sclerosis als fatal neurodegenerative disorder characterized progressive degeneration motor neurons causative pathogenic mechanisms als remain unclear limiting development treatment strategies neuroinflammation immune dysregulation involved disease onset progression several neurodegenerative disorders including als study carried bioinformatic analysis using publicly available datasets gene expression omnibus geo investigate role immune cells genes alterations als singlesample gene set enrichment analysis revealed infiltration multiple types immune cells including macrophages type1 17 t helper cells activated cd4 + cd8 + t cells higher als patients controls weighted gene correlation network analysis identified immune genes associated als gene ontology analysis revealed receptor cytokine activities highly enriched terms pathway analysis showed genes enriched immunerelated pathways cytokinecytokine receptor interaction also pi3kakt mapk signaling pathways nineteen immunerelated genes c3ar1 ccr1 ccr5 cd86 cybb fcgr2b fcgr3a hck itgb2 ptprc tlr1 tlr2 tlr7 tlr8 tyrobp vcam1 cd14 ctss fcer1g identified hub genes based least absolute shrinkage selection operator analysis gene signature differentiate als patients nonneurological controls p 0001 predict disease occurrence auc 0829 training set auc 0862 test set conclusion study provides potential biomarkers als disease diagnosis therapeutic monitoringpmid33994932 pmcpmc8119763 doi103389 fnins2021657465,0.0
nitric oxide target phytochemicals antineuroinflammatory prevention therapy int j mol sci 2021 apr 30 22 9 4771 doi 103390 ijms22094771abstractnitric oxide neurotransmitter mediates activation inhibition inflammatory cascades even though physiological required defense various pathogens excessive can trigger inflammatory signaling cell death reactive nitrogen speciesinduced oxidative stress excessive production activated microglial cells specifically associated neuroinflammatory neurodegenerative conditions alzheimers parkinsons disease amyotrophic lateral sclerosis ischemia hypoxia multiple sclerosis afflictions central nervous system cns therefore controlling excessive production desirable therapeutic strategy managing various neuroinflammatory disorders recently phytochemicals attracted considerable attention potential counteract excessive production cns disorders moreover phytochemicals nutraceuticals typically safe effective review discuss mechanisms production involvement various neurological disorders revisit number recently identified phytochemicals may act inhibitors review may help identify novel potent antiinflammatory agents can downregulate specifically neuroinflammation neurodegenerationpmid33946349 doi103390 ijms22094771,0.0
osteopathia striata mandible cranial sclerosis case report review literature j korean assoc oral maxillofac surg 2021 apr 30 47 2 141144 doi 105125 jkaoms2021472141abstractosteopathia striata cranial sclerosis oscs bone dysplasia characterized linear striated pattern sclerosis especially long bones cranial sclerosis variable clinical findings distinctive radiological findings multiple oral dental findings associated disease can seen dental medical imaging head neck dentists clinicians must familiar signs differentiate pathosis erroneous radiographs following case present patient oscs presented university florida college dentistry multiple craniofacial manifestations syndrome seen panoramic radiograph one commonly requested radiographs dentistspmid33911047 doi105125 jkaoms2021472141,0.0
curcuminprimed human bmscderived extracellular vesicles reverse il1induced catabolic responses oa chondrocytes upregulating mir1263p background curcumin antiinflammatory effects qualifies potential candidate treatment osteoarthritis oa however curcumin limited bioavailability extracellular vesicles evs released multiple cell types act molecule carrier intercellular communication assume evs can maintain bioavailability stability curcumin encapsulation evaluated modulatory effects curcuminprimed human h bmscderived evs curevs il1 stimulated human osteoarthritic chondrocytes oach methodscelltiterblue viability ctb caspase 3 7 live dead assays used determine range cytotoxic curcumin concentrations hbmsc oach curevs control evs harvested cell culture supernatants hbmsc ultracentrifugation western blotting wb transmission electron microscopy nanoparticle tracking analysis performed characterize evs intracellular incorporation evs derived phk26 labeled curcuminprimed control hbmsc tested adding labeled evs oach cultures oach prestimulated il1 followed curev control ev treatment 24 h subsequent analysis viability apoptosis migration scratch assay relative expression selected anabolic catabolic genes assessed qrtpcr furthermore wb performed evaluate phosphorylation erk1 2 pi3k akt p38mapk oach effect hsamir1263p expression il1induced oach determined using ctb caspase 3 7 live dead assays wbresultscurevs promoted viability reduced apoptosis il1stimulated oach attenuated il1induced inhibition migration furthermore curevs increased gene expression bcl2 acan sox9 col2a1 decreased gene expression il1b il6 mmp13 col10a1 il1stimulated oach addition phosphorylation erk1 2 pi3k akt p38 mapk induced il1 prevented curevs curevs increased il1reduced expression hsamir1263p hsamir1263p mimic reversed effects il1conclusioncurevs alleviated il1induced catabolic effects oach promoting viability migration reducing apoptosis phosphorylation erk1 2 pi3k akt p38 mapk thereby modulating proinflammatory signaling pathways treatment oach curevs followed upregulation expression hsamir1263p involved modulation anabolic response oach evs may considered promising drug delivery vehicles curcumin helping alleviate oa,0.0
prediction multiple sclerosis disease using machine learning classifiers comparative study j prev med hyg 2021 apr 29 62 1 e192e199 doi 1015167 24214248 jpmh20216211651 ecollection 2021 marabstractintroduction hamedan province one irans highrisk regions multiple sclerosis ms early diagnosis ms based accurate system can control disease aim study compare performance four machine learning techniques traditional methods predicting ms patientsmethods study used information regarding 200 patients casecontrol study conducted hamadan western iran 2013 2015 performance six classifiers used compare performance terms sensitivity specificity positive predictive value ppv negative predictive value npv positive likelihood ratio lr+ negative likelihood ratio lr total accuracyresults random forest rf model illustrated better performance among models scenarios greater specificity 067 ppv 068 total accuracy 068 influential diagnostic factors ms age birth season genderconclusions findings showed despite six methods performed almost similarly rf model performed slightly better terms different criteria prediction accuracy accordingly approach effective classifier predicting ms early stage control diseasepmid34322636 pmcpmc8283630 doi1015167 24214248 jpmh20216211651,0.0
protective genes pathways alzheimers disease moving towards precision interventions abstractalzheimers disease ad progressive neurodegenerative disorder characterized neurodegeneration cognitive impairment eventual inability perform daily tasks etiology alzheimers complex numerous environmental genetic factors contributing disease lateonset ad highly heritable 60 80 40 risk loci ad identified via large genomewide association studies common variants small effect sizes although discoveries provided novel insight biological contributors ad diseasemodifying treatments remain elusive recently concepts resistance pathology resilience downstream consequences pathology particular interest alzheimers field studies continue identify individuals evade pathology disease even late life individuals neuropathological features ad evade downstream neurodegeneration cognitive impairment hypothesized shift focus alzheimers risk resilience presents opportunity uncover novel biological mechanisms ad identify promising therapeutic targets disease review will highlight selection genes variants reported confer protection ad within literature will also discuss evidence biological underpinnings behind protective effect focus genes involved lipid metabolism cellular trafficking endosomal lysosomal function synaptic function inflammation finally offer recommendations areas field can rapidly advance towards precision interventions leverage ideas protection resilience development novel therapeutic strategies,0.0
impact cell type contextdependent regulatory variants human immune traits background vast majority traitassociated variants identified using genomewide association studies gwas noncoding therefore assumed impact gene regulation however majority traitassociated loci unexplained regulatory quantitative trait loci qtls resultswe perform comprehensive characterization putative mechanisms gwas loci impact human immune traits harmonizing four major immune qtl studies identify 26 271 expression qtls eqtls 23 121 splicing qtls sqtls spanning 18 immune cell types colocalization analyses qtls traitassociated loci 72 gwas reveals genetic effects rna expression splicing immune cells colocalize 404 gwas loci immunerelated traits many cases increasing fraction colocalized loci two fold compared previous studies notably find largest contributors increase splicing qtls colocalize average 14 gwas loci colocalize eqtls contrast find cell typespecific eqtls eqtls small effect sizes contribute new colocalizations investigate 60 gwas loci remain unexplained collect h3k27ac cuttag data rheumatoid arthritis healthy controls find largescale differences immune cells different disease contexts including regions overlapping unexplained gwas lociconclusionaltogether work supports rna splicing important mediator genetic effects immune traits suggests must expand study regulatory processes disease contexts improve functional interpretation yet unexplained gwas loci,0.0
novel tools investigative approaches study oligodendrocyte precursor cells ng2glia cns development disease front cell neurosci 2021 apr 29 15673132 doi 103389 fncel2021673132 ecollection 2021abstractoligodendrocyte progenitor cells opcs also referred ng2glia proliferative cell type adult central nervous system primary role opcs serve progenitors oligodendrocytes recent years become increasingly clear opcs fulfil number functions indeed independent role stem cells evident opcs can regulate metabolic environment directly interact modulate neuronal function maintain blood brain barrier bbb regulate inflammation review article discuss stateoftheart tools investigative approaches used characterize biology function opcs functional genetic investigation single cell sequencing lineage tracing functional imaging discuss important discoveries uncovered techniques functional spatial opc heterogeneity novel opc marker genes interaction opcs cells types opcs integrate respond signals neighboring cells finally review use vitro assay assess opc functions methodologies promise lead ever greater understanding enigmatic cell type turn will shed light pathogenesis potential treatment strategies number diseases multiple sclerosis ms gliomaspmid33994951 pmcpmc8116629 doi103389 fncel2021673132,0.0
altered expression profile baff receptors peripheral blood b lymphocytes graves disease background b lymphocyte activating factor baff growth factor regulating b lymphocytes survival maturation serum baff levels elevated patients affected autoimmune thyroid diseases aitd including graves disease gd hashimotos thyroiditis ht aim study explore association expression levels baff receptors aitdmethodsfiftytwo gd patients 39 hashimotos thyroiditis ht patients 23 healthy controls hc recruited study serum baff levels measured elisa expression baff receptors including baff receptor 3 br3 transmembrane activator calciummodulating cyclophilin ligand interactor taci b lymphocytes analyzed flowcytometry effects steroids serum baff levels expression br3 taci also observed 10 patients graves orbitopathy go receiving steroids therapyresultsserum baff levels significantly elevated 093 024 ng ml hc 118 033 ng ml gd p 00027 102 024 ng ml ht p 00331 br3 expression peripheral b lymphocytes elevated gd mean mfi 452 206 gd vs 300 087 hc p 00015 taci expression peripheral b lymphocytes decreased gd without significance mean mfi 796 406 gd vs 910 337 hc p 01285 expression br3 taci changed significantly ht patients steroids significantly suppressed serum baff concentrations 118 027 ng ml 097 010 ng ml p 00364 br3 expression go patients mean mfi 626 491 405 158 p 00083 conclusionsaltered expression baff receptor may mediate autoimmunity gd restoring normal expression profile receptors baff new strategy treat gd,0.0
low serum neurofilament light chain values identify optimal responders dimethyl fumarate multiple sclerosis treatment sci rep 2021 apr 29 11 1 9299 doi 101038 s41598021886247abstractserum neurofilament light chains snfl biomarkers disease activity multiple sclerosis ms value predict response treatment association patient immunological profile need explored studied 80 relapsingremitting ms patients initiating dimethyl fumarate dmf treatment snfl levels explored baseline 3 6 12 months single molecule array blood lymphocyte subsets measured baseline 6 months flow cytometry patients followed year classified neda evidence disease activity oda ongoing disease activity neda patients lower snfl levels baseline p 00001 three p 0004 six p 003 months dmf treatment consequently low baseline snfl values 12 pg ml increased probability neda 58 ci 182156 p 0002 correcting disease activity previous year associated significant reductions central memory cd4+ t lymphocytes interferongamma+ cd8+ t lymphocytes natural killer t cells memory b cells upon dmf treatment highest differences memory b cells p 00001 shows low baseline snfl values identify ms patients higher probability optimal response dmf reduction effector immune cellspmid33927255 doi101038 s41598021886247,0.0
agedependent outcome analysis microvascular decompression percutaneous thermocoagulation trigeminal neuralgia background trigeminal neuralgia tn severe pain condition common facial neuralgia microvascular decompression mvd presents excellent treatment neurovascular compression cases percutaneous thermocoagulation pt ganglion gasseri alternative option study aimed evaluate postoperative complication rate outcome treatment strategies related patients agemethodsthe medical records patients diagnosis trigeminal neuralgia undergoing mvd pt ganglion gasseri january 2007 september 2017 reviewed determine efficacy complication rate methods regard patients ageresultsseventynine patients underwent mvd surgery 39 pt mean age patients mvd group 61 years 73 years pt group 59 50 female patients nervevessel conflict identified 78 987 mvd 17 436 pt patients preoperative mri charlson comorbidity index significantly higher pt group 24 18 versus 38 18 p 0001 barrow pain score bps last followup demonstrated higher scores pt p 0007 complication rate markedly higher pt group mostly due facial hypesthesia 846 versus 278 p 0001 mean symptomfree survival significantly shorter pt group 9 vs 26 months p 0001 remained statistically significant stratified age groups 65 years older 9 vs 18 months p 0001 duration symptoms 1005 95 ci 10001010 primary procedure 6198 95 ci 265014496 patient age 1033 95 ci 10021066 postoperative complication rate 2777 95 ci 13095890 associated treatment failureconclusionin patient series mvd confirmed excellent treatment option independent patients age however pt effective procedure time pain recurrence shorter favorable outcome bps 1 2 rate lower compared mvd hence mvd preferred treatment pt remain alternative selected cases latter possible elderly patient per se,0.0
application framework guide genetic testing communication across clinical indications background genetic information increasingly relevant across healthcare traditional genetic counseling gc may limit access genetic information may information support individuals need report application clinical implications framework consistently integrate genetics expertise useful patientsmethodsthe clinical genome resources clingen consent disclosure recommendations cadre workgroup designed rubrics guide pre postgenetic test communication using standard set testing indications pre posttest rubrics applied 40 genetic conditions testing modalities diverse features including variability levels penetrance clinical actionability evidence supporting genedisease relationship final communication recommendations reached group consensusresultscommunication recommendations determined 478 unique conditionindication testingindication pairs half conditions indications 238 478 targeted discussions moderate communication depth recommended starting communication level pre posttest conversations traditional gc recommended pretest adultonset neurodegenerative conditions individuals personal history posttest conditions genetic testing revealed molecular diagnosis situations likely higher complexity uncertainty brief communication approach recommended straightforward conditions indications eg familial hypercholesterolemia familial variant testing conclusionsthe cadre recommendations provide guidance clinicians determining depth pre posttest communication strategically aligning anticipated needs patients starting communication approach shorter targeted discussions brief communications suggested many tests indications longer traditional gc consultations reserved patients complex uncertain situations detailed information education psychological support can beneficial future studies cadre communication framework will essential determining cadreinformed care supports quality patient experience improving access genetic information across healthcare,0.0
orbital varix rare case unilateral exophthalmos case report ann med surg lond 2021 apr 29 66102346 doi 101016 jamsu2021102346 ecollection 2021 junabstractthe etiologies unilateral exophthalmos multiple rarely represented intra extraconical vascular mass orbitopalpebral varixes rare 2 orbital masses represent main cause unilateral intermittent exophthalmos often inflammatory nature report case right orbitopalpebral varix 65yearold adult particular history evolving 2 years ophthalmological examination showed right palpebral mass extended right external canthus palpebral collateral circulation moderate right ptosis exophthalmos nonaxial nonpulsatile without thrill painless without complication without visual deficit vascular mass suspected mri revealed right orbitopalpebral varix temporal extension confirmed angiomri latter also allowed search cerebral venous malformation encephalocele bone defect associated also eliminate differential diagnoses tumor arteriovenous fistula color doppler ultrasound proclive position confirmed diagnosis orbital varices preventive lowdose anticoagulant treatment started avoid thrombosis therapeutic abstention absence complications rigorous monthly followup consultation ensured orbitopalpebral varices characterized extensive posterior intraorbital character often evolution imposes strict surveillance case complication thrombosis hemorrhage pain compressive signs optic nerve surgical removal sclerosis varix can envisaged disappointing results recurrence hemorrhage pmid34026106 pmcpmc8134027 doi101016 jamsu2021102346,0.0
effectiveness safety dimethyl fumarate progressive multiple sclerosis mult scler j exp transl clin 2021 apr 29 7 2 20552173211010832 doi 101177 20552173211010832 ecollection 2021 aprjunabstractbackground limited data analyzing safety effectiveness dimethyl fumarate dmf progressive multiple sclerosis pms populationobjective analyze safety effectiveness dmf patients pmsmethods used cox proportional hazards models compare time confirmed worsening improvement expanded disability status scale edss timed 25foot walk t25fw patients treated dmf glatiramer acetate ga least one yearresults included 46 patients treated dmf 42 patients treated ga safety tolerability ga dmf consistent established profiles difference confirmed edss progression trend towards reduced t25fw seen dmf compared ga adjustment hr 086 95 ci037 198 p 072 hr 060 95 ci027 134 p 021 respectively conclusion dimethyl fumarate showed trend towards reduction t25fw evidence clinically significant impact edss small sample precluded definitive determinationpmid33996142 pmcpmc8108088 doi101177 20552173211010832,0.0
implication reticulons rtns neurodegenerative diseases molecular mechanisms potential diagnostic therapeutic approaches int j mol sci 2021 apr 28 22 9 4630 doi 103390 ijms22094630abstractreticulons rtns crucial regulatory factors central nervous system cns well immune system play pleiotropic functions cns rtns transmembrane proteins mediating neuroanatomical plasticity functional recovery central nervous system injury diseases moreover rtns particularly rtn4 rtn3 involved neurodegeneration neuroinflammation processes crucial role rtns development several neurodegenerative diseases including alzheimers disease ad multiple sclerosis ms amyotrophic lateral sclerosis als neurological conditions brain injury spinal cord injury attracted scientific interest reticulons particularly rtn4a nogoa provide understanding early pathogenesis neurodegenerative disorders potential therapeutic targets may offer effective treatment inhibit disease progression review focuses molecular mechanisms functions rtns potential usefulness clinical practice diagnostic tool therapeutic strategypmid33924890 doi103390 ijms22094630,0.0
family planning decision making people multiple sclerosis front neurol 2021 apr 28 12620772 doi 103389 fneur2021620772 ecollection 2021abstractintroduction majority people diagnosed ms childbearing child fathering age therefore family planning important issue women men ms fertility course pregnancy affected ms however people ms pwms may concerns will greater risk complications mother adverse pregnancy outcomes either due disease ongoing medication survey aimed understand family planning decision making pwms related unmet educational needs methods total 332 pwms across usa uk france germany italy spain recruited specialist patient panel agency participate smartphoneenabled standing panel 80question survey focussed decision making information sources pwms regarding family planning well behavior pregnancy male patients ms respond specific questions pregnancy survey results directly compared 2016 us 2010 un census data results pwms likely children general population particularly subgroup patients aged 3645 years total 56 pwms reported disease affected different degrees impact family planning decision making 21 significantly changed plans timing pregnancy number children 14 decided children participants indicated healthcare professionals primary source information family planning 81 responses timing planned pregnancy considered selecting treatment 78 participants conclusion ms found significantly impact family planning decision making pwms significantly less likely children comparison general populationpmid33995240 pmcpmc8113643 doi103389 fneur2021620772,0.0
hlaa21restricted ecm1derived epitope la dc crossactivation priming cd8+ t nk cells novel therapeutic tumour vaccine background cd8+ t cellmediated adaptive cellular immunity natural killer nk cellmediated innate immunity play important roles tumour immunity study aimed develop therapeutic tumour vaccines based doubleactivation cd8+ t nk cellsmethodsthe immune epitope database molecular operating environment software enzymelinked immunosorbent assay used epitope identification flow cytometry confocal microscopy uplcqtofms rnaseq utilized evaluating immunity pbmcderived dcs cd8+ t nk cells related pathways hlaa21 transgenic mice combined immunologically reconstituted tumourbearing mice used examine antitumour effect safety epitope vaccinesresultswe identified novel hlaa21restricted extracellular matrix protein 1 ecm1 derived immunodominant epitopes la induced potent immune response also found laloaded dcs upregulated frequency cd3+ cd8+ t cells cd45ro+ cd69+ activated memory t cells cd3 cd16+ cd56+ nk cells demonstrated cytotoxic granule release la dcctls la dcnk cells cytotoxicity tumour cells microtissue blocks via predominant ifn perforin granzyme b cell death pathway investigating mechanism lamediated cd8+ t activation found la internalized dcs phagocytosis formed lamhci complex presented onto dc surface recognition t cell receptor upregulate zap70 phosphorylation levels activate cd8+ t cells dcctl interactions addition lamediated dcnk crosstalk stimulation tlr4p38 mapk pathway increased mica b expression dcs interact nkg2d nk activation promisingly la activate cd8+ t cells nk cells simultaneously via interacting dcs suppress tumours vivo moreover safety la confirmedconclusionslainduced immune antitumour activity dc crossactivation cd8+ t nk cells demonstrated proofofconcept evidence capability safety novel therapeutic tumour vaccine,0.0
tankyrases modulators protumoral functions molecular insights therapeutic opportunities abstracttankyrase 1 tnks1 tankyrase 2 tnks2 two homologous proteins gaining increasing importance due implication multiple pathways diseases cancer tnks1 2 interact large variety substrates ankyrin ank domain recognizes sequence present substrates tankyrase called tankyrase binding motif tbm one main functions tankyrases regulation protein stability process parylationdependent ubiquitination pardu nonetheless functions less studied also essential order understand role tankyrases many pathways review concentrate different tankyrase substrates analyze depth biological consequences derived interaction tnks1 2 also examine concept canonical noncanonical tbms finally focus information role tnks1 2 different tumor context along benefits limitations current tnks inhibitors targeting catalytic parp domain novel strategies develop inhibitors ankyrin domain available data indicates need deepening knowledge tankyrases elucidate improve current view role parp family members get inhibitors better therapeutic safety profile,0.0
evaluation prolonged walking persons multiple sclerosis reliability spatiotemporal walking variables 6minute walk test sensors basel 2021 apr 28 21 9 3075 doi 103390 s21093075abstractbackground walking disorders represent disabling condition persons multiple sclerosis pwms several studies showed good reliability 6min walk test 6mwt ie especially distance traveled little known reliability spatiotemporal st variables 6mwtobjective evaluate testretest reliability st variables perceived exertion 6mwt pwms comparable healthy personsmethods explored three 1min intervals initial 01 middle 230330 end 56 6mwt six st variables perceived exertion measured respectively using gaitrite system borg scale measurements performed twice 1 week apart testretest effects assessed using intraclass correlation coefficient icc weighted kapparesults fortyfive pwms 24 healthy persons included testretest reliability st variables values goodtoexcellent pwms icc range 08580919 moderatetoexcellent healthy persons icc range 05690946 testretest reliability values perceived exertion fair pwms weighted kappa range 02790376 substantial healthy persons weighted kappa range 07340788 conclusion measurement st variables 6mwt intervals reliable applicable clinical practice research adapt rehabilitation care pwmspmid33925075 doi103390 s21093075,0.0
soluble epoxide hydrolase inhibitor 1trifluoromethoxyphenyl3 1propionylpiperidin4yl urea ameliorates experimental autoimmune encephalomyelitis int j mol sci 2021 apr 28 22 9 4650 doi 103390 ijms22094650abstractpolyunsaturated fatty acids pufas essential fas human health cytochrome p450 oxygenates pufas produce antiinflammatory painresolving epoxy fatty acids epfas oxylipins whose epoxide ring opened soluble epoxide hydrolase seh ephx2 resulting formation toxic proinflammatory vicinal diols dihydroxyfas pharmacological inhibition seh promising strategy treatment pain inflammation cardiovascular diseases conditions tested efficacy potent selective seh inhibitor 1trifluoromethoxyphenyl3 1propionylpiperidin4yl urea tppu animal model multiple sclerosis ms experimental autoimmune encephalomyelitis eae prophylactic tppu treatment significantly ameliorated eae without affecting circulating white blood cell counts tppu accumulated spinal cords scs correlated plasma tppu concentration targeted lipidomics eae scs plasma identified tppu blocked production dihydroxyfas efficiently increased epfa species including 12 13 epoxyoctadecenoic acid 12 13 epome 17 18 epoxyeicosatrienoic acid 17 18 epete tppu alter levels cyclooxygenase cox1 2 metabolites increased 12hydroxyeicosatetraenoic acid 12hete 12 15lipoxygenase metabolites analytical results consistent seh inhibitors reduce neuroinflammation accelerate antiinflammatory responses providing possibility seh inhibitors used disease modifying therapy well msassociated pain reliefpmid33925035 doi103390 ijms22094650,0.0
aberrant complement system activation neurological disorders int j mol sci 2021 apr 28 22 9 4675 doi 103390 ijms22094675abstractthe complement system assembly proteins collectively participate functions healthy diseased brain complement system plays important role maintenance uninjured healthy brain homeostasis contributing clearance invading pathogens apoptotic cells limiting inflammatory immune response however overactivation underregulation entire complement cascade within brain may lead neuronal damage disturbances brain function last decade growing interest role cascading pathway plays neuropathology diverse array brain disorders eg acute neurotraumatic insult chronic neurodegenerative diseases psychiatric disturbances interruption neuronal homeostasis triggers complement activation dysfunction complement promotes diseasespecific response may either beneficial detrimental effects despite recent advances explicit link complement component regulation brain disorders remains unclear therefore comprehensible understanding relationships different stages diseases provide new insight potential therapeutic targets ameliorate slow progression currently intractable disorders nervous system hence aim review provide summary literature emerging role complement system certain brain disorderspmid33925147 doi103390 ijms22094675,0.0
kinesiophobia stroke patients multiple sclerosis parkinson#39 s disesase diagnostics basel 2021 apr 28 11 5 796 doi 103390 diagnostics11050796abstractbackground stroke s multiple sclerosis ms parkinsons disease pd chronic neurological diseases challange public health represent real social problem physical activity pa improves functional performance reduces various symptoms pd ms stroke reduced neurological impairment patients provides chance independence one main obstacles successful rehabilitation patients movement passivity reason might psychological aspects particular fear movementkinesiophobia aim determine many patients s ms pd suffer kinsiophobia factors influence processmethods fifty patients stroke eighty one ms patients sixty one pd patients consecutively recruited hospital outpatients clinics sociodemographic data self assesment fitness visual analogue scale vas pain tampa scale kinesiophobia tsk modified baecke questionnarie older adults physical activity collected score 37 considered indicate high level kinesiophobia according tskresults high level kinesiophobia shown 6667 subjects tsk medians particular illnesses cutoff score amounted s4250 points ms38 points pd4200 points regression showed 15 fluctuation variance r2 01498 p 00001 regression factor showed mobility selfassessment b 02137 age b 00065conclusions kinesiophobia among patients suffering s ms pd concerns subjects predictors kinesiophobia limitations connected functioning age meaning kinesiophobia neurological disorders requires researchpmid33924856 doi103390 diagnostics11050796,0.0
acrolein scavenger dimercaprol offers neuroprotection animal model parkinsons disease implication acrolein trpa1 background mechanisms underlying lesions dopaminergic da neurons essential pathology parkinsons disease pd largely unknown although oxidative stress recognized key factor previously shown prooxidative aldehyde acrolein critical factor pd pathology acrolein scavenger hydralazine can reduce elevated acrolein mitigate da neuron death alleviate motor deficits 6hydroxydopamine 6ohda rat model hypothesize structurally distinct acrolein scavenger dimercaprol dp can also offer neuroprotection behavioral benefitsmethodsdp used lower elevated levels acrolein basal ganglia 6ohda rats acrolein levels related pathologies measured immunohistochemistry locomotor behavioral effects 6ohda injections dp treatment examined using open field test rotarod test pain assessed using mechanical allodynia cold hypersensitivity plantar tests finally effects dp assessed vitro sknsh dopaminergic cells exposed acroleinresultsdp reduced acrolein reversed upregulation painsensing transient receptor potential ankyrin 1 trpa1 channels substantia nigra striatum cortex dp also mitigated motor sensory deficits typical pd addition dp lowered acrolein protected dalike cells vitro acroleins ability upregulate trpa1 also verified vitro using cell linesconclusionsthese results elucidated acroleinmediated pathogenesis reinforced critical role acrolein pd providing strong arguments antiacrolein treatments novel feasible strategy combat neurodegeneration pd considering extensive involvement acrolein various nervous system illnesses beyond antiacrolein strategies may wide applications broad impacts human health,0.0
knock specific maternal vitellogenins zebrafish danio rerio evokes vital changes egg proteomic profiles resemble phenotype poor quality eggs background previously reported results crispr cas9 knockout ko typei typeiii vitellogenins vtgs zebrafish provided first experimental evidence essentiality disparate functioning vtgs different stages early development however specific contributions different types vtg major cellular processes remained investigated present study employed liquid chromatography tandem mass spectrometry lcms ms meet deficit proteomic profiles zebrafish eggs lacking three typei vtgs simultaneously vtg1ko lacking type iii vtg vtg3ko compared wild type wt eggs obtained spectra searched zebrafish proteome database identified proteins quantified based normalized spectral countsresultsthe vtgko caused severe changes proteome 1cell stage zebrafish eggs changes disclosed molecular signatures highly resembled proteomic phenotype poor quality zebrafish eggs reported prior studies proteomic profiles vtgko eggs perturbations abundances hundreds proteins revealed unique noncompensable contributions multiple vtgs protein energy homeostasis lack contribution appears significant impact endoplasmic reticulum mitochondrial functions thus embryonic development even zygotic genome activation increased endoplasmic reticulum stress redox detox activities glycolysis gluconeogenesis enrichment cellular proliferation human neurodegenerative disease related activities vtg1 vtg3ko eggs found indicators aforementioned conditions distinctive increase apoptosis parkinson disease pathways well decrease lipid metabolism related activities vtg3ko eggs implies compelling roles vtg3 least abundant form vtgs vertebrate eggs mitochondrial activities several differentially abundant proteins representing altered molecular mechanisms identified strong candidate markers studying details mechanisms early embryonic development zebrafish possibly vertebratesconclusionsthese findings indicate global egg proteome subject extensive modification depending presence absence specific vtgs modifications can major impact developmental competence,0.0
retinal thickness analysis progressive multiple sclerosis patients treated epigallocatechin gallate optical coherence tomography results supremes study front neurol 2021 apr 28 12615790 doi 103389 fneur2021615790 ecollection 2021abstractbackground epigallocatechin gallate egcg antiinflammatory agent proven neuroprotective properties animal models multiple sclerosis ms optical coherence tomography oct assessed retinal thickness analysis can reflect treatment responses ms objective analyze influence egcg treatment retinal thickness analysis secondary exploratory outcomes randomized controlled sunphenon progressive forms ms trial supremes nct00799890 methods supremes patients underwent oct heidelberg spectralis device subset visits determined peripapillary retinal nerve fiber layer prnfl thickness 12 ring scan around optic nerve head thickness ganglion cell inner plexiform layer gcip inner nuclear layer inl within 6 mm diameter grid centered fovea macular volume scan longitudinal oct data available exploratory analysis 31 supremes participants 12 19 primary secondary progressive ms ppms spms mean age 51 7 years 12 female mean time since disease onset 16 11 years tested null hypothesis treatmenttime interaction using nonparametric analysis longitudinal data factorial experiments results 2 years significant differences longitudinal retinal thickness changes egcg treated placebo arms oct parameter mean change confidence interval ecgc vs placebo prnfl 083 129 m vs 064 156 m p 0156 gcip 067 067 m vs 014 047 m p 0476 inl 006 058 m vs 022 041 m p 0455 conclusion retinal thickness analysis reveal neuroprotective effect egcg line results main supremes trial study probably underpowered detect effect clinical trial registration wwwclinicaltrialsgov identifier nct00799890pmid33995239 pmcpmc8113620 doi103389 fneur2021615790,1.0
strain sex differences somatosensation sociability experimental autoimmune encephalomyelitis brain behav immun health 2021 apr 28 14100262 doi 101016 jbbih2021100262 ecollection 2021 julabstractmultiple sclerosis ms immunemediated disease results major locomotor deficits however recent studies revealed fatigue slow processing speed memory impairment top variables impacting employment status ms patients suggest cognitive effects may greater impact productivity lifestyle quality life diseaserelated motor deficits however debilitating nonlocomotive effects largely overlooked rodent models disease experimental autoimmune encephalomyelitis eae hypothesized murine eae can also used assess nonlocomotive dysfunctions mood sociability muscle strength balance well potential biases dysfunctions due sex strain actively immunized male female c57bl 6 b6 sjl mice eae evaluated performance deacons weight grip test kondzielas inverted screen test halls rope grip test manual von frey test somatic nociception threechamber social preference paradigm hypothesized eae progression associated changes muscle strength balance pain sociability variations linked sex strain results indicate strain sex influenced differences muscle strength balance eae sex strain impact mechanical nociception regardless eae disease status furthermore sex strain complex effects differences sociability conclusion testing additional modalities eae helps unveil signs symptoms used determine efficacy drug treatment modulation mslike behaviorpmid34589768 pmcpmc8474462 doi101016 jbbih2021100262,0.0
assessment 18 fpbr111 cuprizone mouse model multiple sclerosis diagnostics basel 2021 apr 27 11 5 786 doi 103390 diagnostics11050786abstractthe study aims assess site assessment performance 18fpbr111 neuroinflammation marker cuprizone mouse model multiple sclerosis ms 18fpbr111 pet imaging well evaluated multiple sclerosis applications preclinical clinical research study will help establish potential utility 18fpbr111 pet preclinical ms research future animal future human applications 18fpbr111 pet ct conducted 35 weeks n 7 50 weeks n 7 cuprizone treatment sham control n 3 mouse model subgroup mice underwent autoradiography cryosectioned brain tissue t2 weighted mri performed obtain brain structural data mouse 18fpbr111 uptake assessed multiple brain regions pet autoradiography images correlation autoradiography immunofluorescence staining neuroinflammation f4 80 cd11b measured compared control mice significant 18fpbr111 uptake corpus callosum p 0001 striatum caudate internal capsule p 0001 hippocampus p 005 identified pet images 35 weeks 50 weeks validated autoradiography significant uptake differences detected 35 weeks 50 weeks assessing regions whole although trend increased uptake 50 weeks compared 35 weeks cc high 18fpbr111 uptake regions correlated microglial macrophage locations immunofluorescence staining f4 80 cd11b antibodies 18fpbr111 uptake anatomic locations correlated activated microglia histology cuprizone mouse model ms suggests 18fpbr111 potential vivo evaluation therapy response potential use ms patients animal studiespmid33925560 doi103390 diagnostics11050786,0.0
pupillary response postural demand parkinson#39 s disease front bioeng biotechnol 2021 apr 27 9617028 doi 103389 fbioe2021617028 ecollection 2021abstractbackground individuals parkinsons disease pd may need spend mental physical effort ie cognitive workload maintain postural control pupillary response reflects cognitive workload postural control tasks healthy controls investigated measure postural demand pd objectives compare pupillary response increased postural demand using vision occlusion dual tasking individuals pd healthy controls methods thirtythree individuals pd thirtyfive healthy controls recruited four conditions lasted 60 s involved single balance task eyes open single balance task eyes occluded dual task eyes open dual task eyes occluded dual task comprised auditory stroop test pupillary response recorded using eye tracker balance assessed using force plate twoway repeated measures anova lsd posthoc tests employed compare pupillary response center pressure cop displacement across four conditions individuals pd healthy controls results pupillary response higher individuals pd compared healthy controls p 0009 increased challenging postural conditions groups p 0001 posthoc analysis demonstrated increased pupillary response single balance eyes occluded p 0001 dual task eyes open p 001 dual task eyes occluded p 0001 conditions compared single task eyes open condition conclusion overall pd group increased pupillary response increased postural demand compared healthy controls future pupillary response can potential tool understand neurophysiological underpinnings falls risk pd populationpmid33987171 pmcpmc8111006 doi103389 fbioe2021617028,0.0
distribution gpr17expressing cells correlates white matter inflammation status brain tissues multiple sclerosis patients int j mol sci 2021 apr 27 22 9 4574 doi 103390 ijms22094574abstractin multiple sclerosis ms oligodendrocyte precursor cells opcs recruited site injury remyelinate damaged axons however patients process often ineffective due defects opc maturation membrane receptor gpr17 timely regulates early stages opc differentiation however reaching highest levels immature oligodendrocytes downregulated allow terminal maturation since several animal models disease gpr17 upregulated aim work characterize gpr17 alterations ms patients developed immunohistochemistry immunofluorescence procedures detection gpr17 human tissues stained postmortem ms brain lesions patients secondary progressive ms control subjects inflammatory activity lesion evaluated immunohistochemistry myelin protein mog hla antigen classify active chronic inactive chronic active hence assessed distribution gpr17positive cells lesions compared normal appearing white matter nawm white matter wm control subjects data shown marked increase gpr17expressing oligodendroglial cells accumulating nawm moderate inflammation also found furthermore identified two distinct subpopulations gpr17expressing oligodendroglial cells characterized either ramified rounded morphology differently populate wm healthy controls ms patients concluded coordinated presence gpr17 opcs lesion sites inflamed nawm areas suggests gpr17 exploited support endogenous remyelination advanced pharmacological approachespmid33925469 doi103390 ijms22094574,1.0
stepwise target controllability identifies dysregulations macrophage networks multiple sclerosis netw neurosci 2021 apr 27 5 2 337357 doi 101162 netn_a_00180 ecollection 2021abstractidentifying nodes able drive state network crucial understand eventually control biological systems despite recent advances identification remains difficult huge number equivalent controllable configurations even relatively simple networks based evidence many applications essential test ability individual nodes control specific target subset develop fast principled method identify controllable drivertarget configurations sparse directed networks demonstrate approach simulated networks experimental gene networks characterize macrophage dysregulation human subjects multiple sclerosispmid34189368 pmcpmc8233109 doi101162 netn_a_00180,0.0
detection dysbiosis increased intestinal permeability brazilian patients relapsingremitting multiple sclerosis int j environ res public health 2021 apr 27 18 9 4621 doi 103390 ijerph18094621abstractdysbiosis associated barrier disruption altered gutbrain communications associated multiple sclerosis ms study evaluated gut microbiota relapsingremitting patients rrms receiving diseasemodifying therapies dmts correlated data diet cytokines levels zonulin concentrations stool samples used 16s sequencing realtime pcr serum used cytokine determination flow cytometry zonulin quantification elisa pearsons chisquare mannwhitney spearmans correlation used statistical analyses detected differences dietary habits well gut microbiota rrms patients predominance akkermansia muciniphila bacteroides vulgatus decreased bifidobacterium interleukin6 concentrations decreased treated patients detected increased intestinal permeability rrms patients compared controls conclude diet plays important role composition gut microbiota intestinal dysbiosis detected rrms patients involved increased intestinal permeability affect clinical response dtms future goal predict therapeutic responses based individual microbiome analyses personalized medicine propose dietary interventions use probiotics microbiota modulators adjuvant therapy enhance therapeutic efficacy dmtspmid33925359 doi103390 ijerph18094621,0.0
astrocytespecific expression interleukin 23 leads aggravated phenotype enhanced inflammatory response b cell accumulation eae model background interleukin 23 critical cytokine pathogenesis multiple sclerosis local impact interleukin 23 course neuroinflammation still well defined characterize effect interleukin 23 cns inflammation recently described transgenic mouse model astrocytespecific expression interleukin 23 gfil23 mice gfil23 mice spontaneously develop progressive ataxic phenotype cerebellar tissue destruction inflammatory infiltrates high amounts b cells prominent subarachnoid perivascular spacemethodsto elucidate local impact cnsspecific interleukin 23 synthesis autoimmune neuroinflammation induced mog3555 experimental autoimmune encephalomyelitis eae gfil23 mice wt mice analyzed mice histology flow cytometry transcriptome analysisresultswe able demonstrate local interleukin 23 production cns leads aggravation chronification eae course severe paraparesis ataxic phenotype moreover enhanced multilocular neuroinflammation present spinal cord also forebrain brainstem predominantly cerebellum accompanied persisting demyelination thereby interleukin 23 creates pronounced proinflammatory response accumulation leukocytes particular b cells cd4+ cells also t cells activated microglia macrophages furthermore transcriptome analysis revealed enhanced proinflammatory cytokine milieu upregulation lymphocyte activation markers costimulatory markers chemokines components complement systemconclusiontaken together gfil23 model allowed breakdown different mechanisms il23 drives neuroinflammation eae model proved useful tool dissect impact interleukin 23 neuroinflammatory models,1.0
galectin3 key player microgliamediated neuroinflammation alzheimer#39 s disease abstractalzheimers disease ad common cause dementia characterized deposition extracellular aggregates amyloid formation intraneuronal tau neurofibrillary tangles microglial activationmediated neuroinflammation one key molecules involved microglial activation galectin3 gal3 recent years extensive studies dissected mechanisms gal3 modulates microglial activation impacting deposition animal models human studies review article focus emerging role gal3 biology pathobiology including origin functions regulating microglial activation neuroinflammation emergence biomarker ad neurodegenerative diseases aspects important elucidate involvement gal3 ad pathogenesis may provide novel insights use gal3 ad diagnosis therapy,0.0
cellular immunology relapsing multiple sclerosis interactions checks balances summarynovel insights basic translational studies reshaping concepts immunopathogenesis multiple sclerosis understanding different inflammatory responses throughout disease course previously cellular immunology relapsing multiple sclerosis considered principally tcell driven however process now understood involve multiple cell types functionally distinct subsets particularly relapsing multiple sclerosis appears involve imbalanced interactions t cells myeloid cells b cells effector regulatory subpopulations major contributors imbalances differ across patients several emerging techniques enable comprehensive immune cell profiling singlecell level revealing substantial functional heterogeneity plasticity influence disease state response treatment findings clinical trials agents successfully limit new multiple sclerosis disease activity trials agents inadvertently exacerbate cns inflammation helped elucidate disease mechanisms better define relevant modes action current immune therapies pave way new therapeutic strategies,0.0
tissue transglutaminase expression associates progression multiple sclerosis neurol neuroimmunol neuroinflamm 2021 apr 27 8 4 e998 doi 101212 nxi0000000000000998 print 2021 julabstractobjective clinical course multiple sclerosis ms variable largely unpredictable pointing urgent need markers monitor disease activity progression recent evidence revealed tissue transglutaminase tg2 altered patientderived monocytes hypothesize blood cellderived tg2 messenger rna mrna can potentially used biomarker patients msmethods peripheral blood mononuclear cells pbmcs 151 healthy controls 161 patients ms tg2 mrna measured correlated clinical mri parameters disease activity annualized relapse rate gadoliniumenhanced lesions t2 lesion volume disease progression expanded disability status scale edss normalized brain volume hypointense t1 lesion volume results pbmcderived tg2 mrna levels significantly associated disease progression ie worsening edss 2 years followup normalized brain volume normalized gray white matter volume total ms patient group baseline patients relapsingremitting ms tg2 expression significantly associated worsening edss scores 2 years followup patients primary progressive pp ms tg2 mrna levels significantly associated edss normalized brain volume normalized gray white matter volume baseline addition tg2 mrna associated t1 hypointense lesion volume patients pp ms baselineconclusion pbmcderived tg2 mrna levels hold promise biomarker disease progression patients msclassification evidence study provides class ii evidence patients ms pbmcderived tg2 mrna levels associated disease progressionpmid33906937 doi101212 nxi0000000000000998,0.0
wellbeing disease severity multiple sclerosis patients following physical activity program abstract introduction multiple sclerosis ms chronic disease central nervous system mainly affects young adults promoting great impact functionality fatigue common symptom associated multiple impairments sensitivity muscle activity neuromotor control balance cognition problemsolving ability ms leads strong functional restrictions particularly context daily living activities well patient participation objective understand implications selfregulation program perception wellbeing mental health ms patients methods set exercises implemented use daily activities supported different studies ms patients patients asked classify severity disease use mental health inventory mhi38 beginning time end time b selfregulation program used statistical package social sciences spss version 25 nonparametric statistical hypothesis test wilcoxon test used analyze variables results mean age 44 years old patients ages 20 58 583 women 375 currently married 67 retired mean level education 125 years correlation perception disease severity psychological wellbeing selfregulation program r 026 p 005 intervention r 037 p 001 suggests low moderate correlation conclusion implementation selfregulatory model promotion physical activity patients ms positive impact clinical rehabilitation wellbeing perception disease severity people,0.0
episodic headache spontaneous hypothermia reveal shapiros syndrome variant effectiveness clonidine therapy background episodic headache spontaneous hypothermia constitute uncommon association well recognized international classification headache disorders ichd3 spontaneous periodic hypothermia also called shapiros syndrome rare disease characterized hypothermia attacks associated hyperhidrosis without triggering factorcase presentationwe report rare case shapiros syndrome variantrevealed episodes headache spontaneous hypothermia witheffectiveness clonidine therapy 76yearold parkinsons disease womanconclusionsin literature apart shapiros syndrome headache withhypothermia seem occur rarely case symptoms may considered rare nonmotor fluctuation ofparkinsons disease,0.0
carsiteii integrated classification algorithm identifying carbonylated sites based kmeans similaritybased undersampling synthetic minority oversampling techniques background carbonylation nonenzymatic irreversible protein posttranslational modification refers side chain amino acid residues attacked reactive oxygen species finally converted carbonyl products studies shown protein carbonylation caused reactive oxygen species involved etiology pathophysiological processes aging neurodegenerative diseases inflammation diabetes amyotrophic lateral sclerosis huntingtons disease tumor current experimental approaches used predict carbonylation sites expensive timeconsuming limited protein processing abilities computational prediction carbonylation residue location protein posttranslational modifications enhances functional characterization proteinsresultsin study integrated classifier algorithm carsiteii developed identify k p r t carbonylated sites resampling method kmeans similaritybased undersampling synthetic minority oversampling technique smoteksu incorporated balance proportions k p r t carbonylated training samples next integrated classifier system rotation forest uses support vector machine subclassifications divide three types feature spaces several subsets carsiteii gained matthews correlation coefficient mcc values 02287 03125 02787 02814 false positive rate values 02628 01084 01383 01313 false negative rate values 02252 00205 00976 00608 k p r t carbonylation sites tenfold crossvalidation respectively independent test dataset carsiteii yield mcc values 06358 02910 04629 03685 false positive rate values 00165 00203 00188 00094 false negative rate values 01026 01875 02037 03333 k p r t carbonylation sites results show carsiteii achieves remarkably better performance currently available prediction toolsconclusionthe related results revealed carsiteii achieved better performance currently available five programs revealed usefulness smoteksu resampling approach integration algorithm convenience experimental scientists web tool carsiteii available http 47100136418081,0.0
tissuespecific role associated downstream signaling pathways adiponectin abstractaccording world health organization metabolic syndrome mets can defined pathological condition characterized abdominal obesity insulin resistance hypertension hyperlipidemia incidence mets keeps rising least 35 usa population suffers mets one worst comorbidities metabolic syndrome cardiovascular diseases significantly amplifies mortality associated syndrome urgent need understand pathophysiology mets find novel diagnosis treatment management mitigate mets associated complications altered circulatory adiponectin levels implicated mets adiponectin numerous biologic functions including antioxidative antinitrative antiinflammatory cardioprotective effects pleiotropic hormone multiple tissues tissuespecific key signaling pathways adiponectin will help finding specific target s blunt pathophysiology metabolic syndrome associated disorders purpose review elucidate tissuespecific signaling pathways adiponectin possibly identify potential therapeutic targets mets well evaluate potential adiponectin biomarker therapeutic option mets,0.0
characteristics variation fecal bacterial communities functions isolated systolic diastolic hypertensive patients background hypertension htn one major cardiovascular risk factors contributes increasing target organ damages cardiovascular morbidity mortality worldwide isolated systolic htn ish isolated diastolic htn idh two important subtypes htn previous researches demonstrated alteration fecal bacteria htn two subtypes order identify whether composition bacterial taxa functional modules shift ish idh performed metagenomic sequencing analysis fecal samples 15 controls 14 ish 11 idhresultscompared control ish idh patients showed decreased gene number bacterial richness evenness although bacterial alterations reach statistical significance shannon index also genus level diversity intestinal flora idh distinguishable ish furthermore taxonomic composition ish idh different healthy control genus species levels patients idh ish confirmed enriched rothia mucilaginosa along reduced clostridium sp asbs410 lastly altered kegg modules significantly decreased idh compared control group sodium transport system ish functions relevant biotin biosynthesis decreasedconclusionsoverall results showed disordered fecal bacteria profiles subjects ish especially idh emphasizing significance early intervention idh,0.0
anomalously warm weather acute care visits patients multiple sclerosis retrospective study privately insured individuals us plos med 2021 apr 26 18 4 e1003580 doi 101371 journalpmed1003580 online ahead printabstractbackground global climate changes response anthropogenic greenhouse gas emissions weather temperature expected become increasingly variable although heat sensitivity recognized clinical feature multiple sclerosis ms chronic demyelinating disorder central nervous system studies examined implications climate change patients diseasemethods findings conducted retrospective cohort study individuals ms ages 1864 years nationwide united states patientlevel commercial medicare advantage claims database 2003 2017 defined anomalously warm weather month local average temperatures exceeded longterm average 15c estimated association anomalously warm weather msrelated inpatient outpatient emergency department visits using generalized loglinear models 75 395 334 individuals identified 106 225 ms majority women 766 aged 3655 years 590 anomalously warm weather associated increased risk emergency department visits risk ratio rr 1043 95 ci 10251063 inpatient visits rr 1032 95 ci 10101054 limited evidence association anomalously warm weather msrelated outpatient visits rr 1010 95 ci 10051015 estimates similar men women strongest among older individuals exhibited substantial variation season region climate zone limitations present study include absence key individuallevel measures socioeconomic position ie race ethnicity occupational status housing quality may determine individuals liveand therefore extent exposure anomalously warm weatheras well propensity seek treatment neurologic symptomsconclusions findings suggest global temperatures rise individuals ms may represent particularly susceptible subpopulation finding implications healthcare providers systemspmid33901187 doi101371 journalpmed1003580,1.0
bloodbrain barrier breakdown nonenhancing multiple sclerosis lesions detected 7tesla mp2rage deltat1 mapping plos one 2021 apr 26 16 4 e0249973 doi 101371 journalpone0249973 ecollection 2021abstractalthough bloodbrain barrier bbb altered multiple sclerosis ms lesions gadolinium enhancement seen acute lesions study aimed investigate gadoliniuminduced changes t1 relaxation time ms lesions 7tesla 7t mri means quantify bbb breakdown nonenhancing ms lesions fortyseven participants ms underwent 7t mri brain magnitudeprepared rapid acquisition 2 gradient echoes mp2rage sequence contrast subtraction pre postcontrast t1 maps used measure t1 relaxation time change t1 gadolinium t1 values interrogated enhancing white matter lesions els nonenhancing white matter lesions nels normal appearing white matter nawm metrics compared clinical data t1 measurable nels median 0139 0304 0174 seconds p 0001 negligible nawm median 0001 0036 0155 seconds p 0516 median t1 nels correlated disability measured expanded disability status scale edss rho 0331 p 0026 multiple measures nel t1 variability also correlated edss nel t1 values greater variable patients progressive forms ms greater ms treatment measurement changes t1 relaxation time caused contrast 7t mp2rage reveals clinically relevant evidence bbb breakdown nels ms data suggests nel t1 evaluated biomarker disease severity treatment effect mspmid33901207 doi101371 journalpone0249973,0.0
longitudinal evaluation novel bche pet tracer early vivo biomarker brain mouse model alzheimer disease theranostics 2021 apr 26 11 13 65426559 doi 107150 thno54589 ecollection 2021abstractpurpose increase butyrylcholinesterase bche activity brain alzheimer disease ad patients animal models ad position enzyme potential biomarker disease however information ability bche serve ad biomarker contradicting also due scarce longitudinal studies bche activity abundance report 11clabeling vivo stability biodistribution longitudinal study bche abundance brains control 5xfad ad model animals using potent bche selective inhibitor 11c 4 positron emission tomography pet combination computerised tomography ct correlate results vivo amyloid beta deposition longitudinally assessed 18f florbetabenpet imaging methods 11c 4 radiolabelled 11cmethylation metabolism studies performed blood brain samples female wild type wt mice biodistribution studies performed female wt mice using dynamic petct imaging specific binding demonstrated ex vivo vivo pet imaging blocking studies female wt 5xfad mice age 7 months longitudinal pet imaging bche conducted female 5xfad mice 4 6 8 10 12 months age compared agematched control animals additionally plaque distribution assessed mice using 18f florbetaben ages 2 5 7 11 months results validated ex vivo staining bche 4 8 12 months 12 months brain samples results 11c 4 produced sufficient radiochemical yield molar activity use pet imaging metabolism biodistribution studies confirmed sufficient stability vivo ability 11c 4 cross blood brain barrier bbb rapid washout brain blocking studies confirmed specificity binding longitudinal pet studies showed increased levels bche cerebral cortex hippocampus striatum thalamus cerebellum brain stem aged ad mice compared wt littermates 18f florbetabenpet imaging showed similar trend plaques accumulation cerebral cortex hippocampus ad animals one observed bche ages 4 8 months contrarily results obtained ex vivo staining lower abundance bche observed vivo 10 12 months 8 months age conclusions bche inhibitor 11c 4 crosses bbb quickly washed brain wt mice comparison ad wt mice shows accumulation radiotracer adaffected areas brain time early disease progression results correspond well accumulation suggesting bche promising early biomarker incipient adpmid33995675 pmcpmc8120209 doi107150 thno54589,0.0
madgan unsupervised medical anomaly detection gan using multiple adjacent brain mri slice reconstruction background unsupervised learning can discover various unseen abnormalities relying largescale unannotated medical images healthy subjects towards unsupervised methods reconstruct 2d 3d single medical image detect outliers either learned feature space high reconstruction loss however without considering continuity multiple adjacent slices directly discriminate diseases composed accumulation subtle anatomical anomalies alzheimers disease ad moreover study shown unsupervised anomaly detection associated either disease stages various ie two types diseases multisequence magnetic resonance imaging mri scansresultswe propose unsupervised medical anomaly detection generative adversarial network madgan novel twostep method using ganbased multiple adjacent brain mri slice reconstruction detect brain anomalies different stages multisequence structural mri reconstruction wasserstein loss gradient penalty + 100 ell _1 losstrained 3 healthy brain axial mri slices reconstruct next 3 onesreconstructs unseen healthy abnormal scans diagnosis average ell _2 loss per scan discriminates comparing ground truth reconstructed slices training use two different datasets composed 1133 healthy t1weighted t1 135 healthy contrastenhanced t1 t1c brain mri scans detecting ad brain metastases various diseases respectively selfattention madgan can detect ad t1 scans early stage mild cognitive impairment mci area curve auc 0727 ad late stage auc 0894 detecting brain metastases t1c scans auc 0921conclusionssimilar physicians way performing diagnosis using massive healthy training data first multiple mri slice reconstruction approach madgan can reliably predict next 3 slices previous 3 ones unseen healthy images first unsupervised various disease diagnosis madgan can reliably detect accumulation subtle anatomical anomalies hyperintense enhancing lesions especially latestage ad brain metastases multisequence mri scans,0.0
testicular steroidogenesis suppressed experimental autoimmune encephalomyelitis rats sci rep 2021 apr 26 11 1 8996 doi 101038 s41598021883055abstractmultiple sclerosis ms autoimmune disease usually occurs reproductive years sexes many male patients ms show lower blood testosterone levels also observed male rats experimental autoimmune encephalomyelitis eae animal model ms better understand causes decreased testosterone production eae investigated expression status genes proteins associated steroidogenesis testes changes number interstitial cells observed eae animals expression insulinlike 3 gene reduced peak disease implying leydig cell functional capacity affected consistent finding expression steroidogenic enzyme genes proteins reduced eae including star cyp11a1 cyp17a1 hsd3b signs testicular inflammation observed recovery steroidogenesis observed injection hcg placental gonadotropin buserelin acetate gonadotropinreleasing hormone analogue peak eae together results consistent hypothesis impaired testicular steroidogenesis originates upstream testes low serum lh main cause decreased testosterone levels eaepmid33903635 doi101038 s41598021883055,0.0
suppression neuroinflammation allosteric agonist positive allosteric modulator 7 nicotinic acetylcholine receptor gat107 background 7 nicotinic acetylcholine receptor 7 nachr negatively regulates synthesis release proinflammatory cytokines immune cells previous studies showed encephalitogenic t cells 7 nachr expression upregulated activation cholinergic system can attenuate experimental autoimmune encephalomyelitis eae gat107 allosteric agonist positive allosteric modulator agopam 7 nachr can produce persistent activation receptor therefore present study investigated effect gat107 neuroinflammation eae animal model used study multiple sclerosis ms via 7 nachr inflammatory pathways involvedmethodseae induced administration myelin oligodendrocyte glycoprotein mog3555 c57bl 6 mice eae mice treated agopam gat107 placebo 9 days starting day eae induction clinical assessment immunological evaluation immune cells cytokine production performedresultsfollowing activation 7 nachr gat107 eae disease severity significantly reduced 70 correlated reduction extent neuroinflammation cns treatment reduced encephalitogenic t cell proliferation production proinflammatory cytokines well increased production antiinflammatory cytokine il10 furthermore expression immune cell markers altered gat107 treatment induced significant reduction macrophages dendritic cells b cells well reduction antimog3555 antibodies additionally gat107 found directly activate 7 nachr murine macrophage raw2647 cells human pbmcs derived ms patients healthy donorsconclusionsour results show gat107 can useful molecule harnessing cholinergic antiinflammatory pathway longlasting wideranging modulation downregulation neuroinflammation eae,1.0
combined central peripheral demyelinating disease good response bcell depleting therapy cureus 2021 apr 26 13 4 e14690 doi 107759 cureus14690abstractcombined central peripheral demyelination ccpd rare disorder characterized demyelinating lesions central peripheral nervous systems following case report 29yearold man presented threemonth history progressive lower upper limb weakness associated facial arm tremor well urinary hesitancy brain spine magnetic resonance imaging showed multiple demyelinating plaques nerve conduction studies revealed evidence demyelination severe prolongation distal motor latencies reduced conduction velocities patient received plasmapheresis highdose corticosteroids lead clinical improvement rituximab infusion protocol subsequently started patient received two cycles significant functional improvement upon use rituximab study reports rare neurological disease entity highlights necessity conducting larger studies optimally demonstrate efficacy rituximab ccpdpmid34055534 pmcpmc8153962 doi107759 cureus14690,1.0
neuroprotective effects fingolimod supplement retina optic nerve mouse model experimental autoimmune encephalomyelitis front neurosci 2021 apr 26 15663541 doi 103389 fnins2021663541 ecollection 2021abstractfavorable effects exerted longterm administration fingolimod therapy multiple sclerosis ms patients reported sporadic side effects reversible macular edema also recorded present study aimed determine whether fingolimod therapy beneficial visual system experimental autoimmune encephalomyelitis eae mice decrease demyelination axon loss optic nerve well cellular infiltration especially recruited macrophages observed eae fingolimod treatment fingolimod administration diminished hypergliosis macroglia including astrocytes mller cells retina optic nerve eae microglia hyperactivated retina optic nerve eae mice compared controls alleviated fingolimod treatment moreover apoptosis retinal ganglion cells rgc oligodendrocytes optic nerve significantly reduced fingolimod treatment compared untreated eae mice results suggested fingolimod exerts neuroprotective antiinflammatory effects retina optic nerve mouse model eae considering paradox favorable side effects fingolimod visual system speculate side effects including macular oedema caused fingolimod ms treatment tendency vasogenic rather hypergliosis optic nerve retina warrants neuroophthalmological investigationpmid33981197 pmcpmc8107225 doi103389 fnins2021663541,1.0
serum neurofilament levels pml risk patients multiple sclerosis treated natalizumab neurol neuroimmunol neuroinflamm 2021 apr 26 8 4 e1003 doi 101212 nxi0000000000001003 print 2021 julabstractobjectives study aimed assess potential serum neurofilament light chain nfl levels predict risk progressive multifocal leukoencephalopathy pml natalizumab ntz treated patients multiple sclerosis ms discriminate pml ms relapsesmethods nfl levels measured single molecule array simoa 4 cohorts 1 prospective cohort patients ms developed pml ntz therapy prepml nonpml ntztreated patients ntzctr 2 cohort patients whose blood collected pml 3 independent cohort nonpml ntztreated patients serum nfl determinations 2 years replication cohort 4 cohort patients whose blood collected exacerbationsresults serum nfl levels significantly increased 2 years ntz treatment prepml patients compared ntzctr prognostic performance serum nfl levels predict pml development 2 years similar ntzctr group replication cohort serum nfl levels also distinguished pml ms relapses 8fold higher pml compared relapsesconclusions results support use serum nfl levels clinical practice identify patients relapsingremitting ms higher pml risk differentiate pml clinical relapses ntztreated patientsclassification evidence study provides class evidence serum nfl levels can identify ntztreated patients ms will develop pml sensitivity 67 specificity 80pmid33903203 doi101212 nxi0000000000001003,0.0
sexspecific dna methylation differences alzheimers disease pathology abstractsex important factor contributes clinical biological heterogeneities alzheimers disease ad regulatory mechanisms underlying sex disparity ad still well understood dna methylation important epigenetic modification regulates gene transcription known involved ad performed first largescale sexspecific metaanalysis dna methylation differences ad neuropathology reanalyzing four recent epigenomewide association studies totaling 1000 postmortem prefrontal cortex brain samples using uniform analytical pipeline cohort employed two complementary analytical strategies sexstratified analysis examined methylationbraak stage associations male female samples separately sexbybraak stage interaction analysis compared magnitude associations different sexes analysis uncovered 14 novel cpgs mapped genes tmem39a tnxb associated ad braak stage sexspecific manner tmem39a known involved inflammation dysregulated type interferon responses immune processes tnxb encodes tenascin proteins extracellular matrix glycoproteins demonstrated modulate synaptic plasticity brain moreover many previously implicated genes ad neuropathology mbp azu1 analysis provided new insights predominately driven effects one sex sexspecific dna methylation differences enriched divergent biological processes integrin activation females complement activation males study implicated multiple new loci biological processes affected ad neuropathology sexspecific manner,0.0
overview venous abnormalities related development lesions multiple sclerosis front neurol 2021 apr 26 12561458 doi 103389 fneur2021561458 ecollection 2021abstractthe etiology multiple sclerosis ms currently understood autoimmune however long history growing evidence disrupted vasculature flow within disease pathology broad review literature related vascular effects ms revealed suggestive role abnormal flow medullary vein system evidence venous involvement multiple sclerosis dates back early pathological work charcot bourneville midnineteenth century pioneering work adams 1980s demonstrated vasculitis within walls veins venules proximal active ms lesions recently magnetic resonance imaging mri used show manifestations central vein precursor development new ms lesions highresolution mri using ferumoxytol used reveal microvasculature previously demonstrated cadaver brains approaches may shed new light structural changes occurring ms lesions material covered review shows multiple pathophysiological events may occur sequentially parallel vicious circle include endothelial damage venous collagenosis fibrin deposition loss vessel compliance venous hypertension perfusion reduction followed ischemia medullary vein dilation local vascular remodeling come conclusion potential source ms lesions due locally disrupted flow turn leads remodeling medullary veins followed endothelial damage subsequent escape glial cells cytokines etc ultimately lead cascade inflammatory demyelinating events ensue course diseasepmid33981281 pmcpmc8107266 doi103389 fneur2021561458,1.0
podocytopathy another image renal affection psle background lupus podocytopathy lp renal affection described systemic lupus erythematosus sle patients nephrotic range proteinuria characterized diffuse foot process effacement without immune deposits glomerular proliferation study describes lp pathological features outcomes pediatric psle patients comparison usual lupus nephritis ln casesmethodologya retrospective cohort study conducted 10year registration 20102019 140 psle patients pediatric department tanta university histopathological analysis light microscopy lm immunofluorescence renal biopsies evaluated according international society nephrology renal pathology society isn rps grading system addition biopsies examined electron microscopy em resultseightysix psle cases 614 renal involvement seventynine biopsies 9186 met classification criteria ln defined isn rps system five biopsies normal mcd two showed focal segmental sclerosis fsgn meet known classification ln hence reevaluated using em revealed diffuse effaced podocytes without glomerular subepithelial endocapillary basement membrane immune deposits classified lupus podocytopathy representing 814 ln biopsies seven cases showed good response steroids complete remission duration 340 195 weeks however case 13 relapses duration follow upconclusionslp spectrum psle association related disease activity initial presentation,0.0
blood oxygenation leveldependent response multiple grip forces multiple sclerosis going beyond main effect movement brodmann area 4a 4p front cell neurosci 2021 apr 26 15616028 doi 103389 fncel2021616028 ecollection 2021abstractthis study highlights importance looking beyond main effect movement study alterations functional response presence central nervous system pathologies multiple sclerosis ms data show ms selectively affects regional bold blood oxygenation level dependent responses variable grip forces gf known anterior posterior ba 4 areas ba 4a ba 4p anatomically functionally distinct also shown healthy volunteers linear first order typical ba 4a nonlinear second fourth order typical ba 4p bold responses different levels gf applied dynamic motor paradigm modeling bold response polynomial expansion applied gfs particular case ba 4a ba 4p investigated healthy volunteers hv ms subjects main effect movement zeroth order analysis showed bold signal greater ms compared healthy volunteers within ba 4 subregions higher order boldgf responses similar ba 4a showed marked alteration ba 4p ms subjects greatest disability showing greatest deviations healthy response profile therefore different behaviors hv ms uncovered polynomial analysis looking beyond main effect movement two ba 4 subregions future studies will investigate source pathophysiology combining present fmri paradigm blood perfusion nonlinear neuronal response analysispmid33981201 pmcpmc8109244 doi103389 fncel2021616028,0.0
myeloid atp citrate lyase regulates macrophage inflammatory responses vitro without altering inflammatory disease outcomes front immunol 2021 apr 26 12669920 doi 103389 fimmu2021669920 ecollection 2021abstractmacrophages highly plastic key regulators inflammation deregulation macrophage activation can lead excessive inflammation seen inflammatory disorders like atherosclerosis obesity multiple sclerosis sepsis targeting intracellular metabolism considered approach reshape deranged macrophage activation dampen progression inflammatory disorders atp citrate lyase acly key metabolic enzyme important regulator macrophage activation using macrophagespecific aclydeficient mouse model investigated role acly macrophages acute chronic inflammatory disorders first performed rna sequencing demonstrate aclydeficient macrophages showed hyperinflammatory gene signatures response acute lps stimulation vitro next assessed endotoxininduced peritonitis myeloidspecific aclydeficient mice show apart increased splenic il6 expression systemic local inflammation affected acly deficiency also obesity chronic lowgrade inflammation wholebody metabolic homeostasis remained largely unaltered mice aclydeficient myeloid cells lastly show macrophagespecific acly deletion affect severity experimental autoimmune encephalomyelitis eae experimental model multiple sclerosis results indicate despite increasing inflammatory responses vitro macrophage acly deficiency worsen acute chronic inflammatory responses vivo collectively results indicate caution warranted prospective longterm treatments inflammatory disorders macrophagespecific acly inhibitors together earlier observation myeloid acly deletion stabilizes atherosclerotic lesions findings highlight therapeutic targeting macrophage acly can beneficial inflammatory disorderspmid33981315 pmcpmc8107722 doi103389 fimmu2021669920,0.0
tolllike receptors gene polymorphisms autoimmune disease front immunol 2021 apr 26 12672346 doi 103389 fimmu2021672346 ecollection 2021abstracttolllike receptors tlrs important initiators immune response innate acquired evidence suggests gene polymorphisms within tlrs cause malfunctions certain key tlrrelated signaling pathways subsequently increases risk autoimmune diseases illustrate discuss current findings role tolllike receptor gene polymorphisms numerous autoimmune diseases review type 1 diabetes mellitus graves disease rheumatoid arthritis systemic lupus erythematosus multiple sclerosis study genetic variation tlrs different populations shown complex interaction immunity environmental factors interaction suggests tlr polymorphisms affect susceptibility autoimmune diseases differently various populations identification tolllike receptor gene polymorphisms can expand understanding pathogenesis autoimmune diseases will subsequently guide effective medical management provide insight prognosis advanced treatmentspmid33981318 pmcpmc8107678 doi103389 fimmu2021672346,0.0
facial nerve regeneration using silicone conduits filled ammoniafunctionalized graphene oxide frankincenseembedded hydrogel background silicone tube st conduits accepted therapeutic alternative direct nerve suturing treatment nerve injuries however search optimal adjuncts maximize outcomes still ongoing frankincense fr graphene oxide go cited neuroregenerative compounds literature study assesses efficacy materials using st conduit rat facial nerve motor neuron axotomy model distal stylomastoid foramenmethodsammoniafunctionalized graphene oxide nh2go fr extract embedded collagenchitosan hydrogel injected inside st st inserted gap axotomized nerve stumps return function eye closure blinking reflex vibrissae movements assessed compared control groups 30 days following axotomy assess histological properties regenerated nerves biopsies harvested distal axotomy site visualized light fluorescence microscopy using lfb antimbp marker respectivelyresultsthere significant difference behavioral test results groups histological analysis nerve sections revealed increased number regenerating axons mean axon diameter nh2go group decreased myelin surface area fr group using nh2go fr resulted increased number regenerated axons myelin thickness compared hydrogel groupconclusionsthe findings suggest synergistic effect substances axon regrowth notably myelin regeneration fr supposedly decreases myelin synthesis,1.0
broadening understanding genetic risk scleroderma systemic sclerosis querying chromatin architecture surrounding risk haplotypes background genetic variants human leukocyte antigen hla locus contribute risk developing scleroderma systemic sclerosis ssc however replicated loci also contribute genetic risk ssc unknown whether genetic risk nonhla loci acts primarily vasculature immune system fibroblasts relevant cell types used cistrome database investigate epigenetic landscapes surrounding 11 replicated ssc associated loci determine whether snps loci may affect regulatory elements whether likely impact specific cell type methodswe mapped 11 replicated snps haplotypes sought determine whether significant enrichment h3k27ac h3k4me1 marks epigenetic signatures enhancer function haplotypes queried pathologically relevant cell types b cells endothelial cells fibroblasts monocytes t cells identified topologically associated domains tads encompass ssc risk haplotypes primary t cells identify full range genes may influenced ssc causal snps used gene ontology analyses genes within tads gain insight immunologic functions might affected ssc causal snps resultsthe sscassociated haplotypes enriched p value 001 h3k4me1 h3k27ac marks monocytes enrichment one two histone marks found b cells fibroblasts t cells enrichment identified endothelial cells ontological analyses genes within tads encompassing risk haplotypes showed enrichment regulation transcription protein binding activation t lymphocytes proliferation immune cells conclusionsthe 11 nonhla ssc risk haplotypes queried highly enriched h3k4me1 h3k27acmarked regulatory elements broad range immune cells fibroblasts furthermore immune cells risk haplotypes belong larger chromatin structures encompassing genes regulate wide array immune processes associated ssc pathogenesis though importance vasculature pathobiology ssc widely accepted unable find evidence genetic influences endothelial cell function regions,0.0
dalfampridine improves slowed processing speed multiple sclerosis patients mild motor disability post hoc analysis randomized controlled trial ther adv neurol disord 2021 apr 24 1417562864211011286 doi 101177 17562864211011286 ecollection 2021abstractobjective evaluate baseline characteristics predictive improving information processing speed multiple sclerosis ms relationship cognitive motor response dalfampridine da treatmentmethods post hoc analysis randomized doubleblind placebocontrolled trial patients ms randomized receive da 10 mg placebo twice daily 12 consecutive weeks include data 71 patients arm treated da according median value symbol digit modalities test sdmt response patients categorized full responders fr partially responders pr results higher possibility fr presence baseline lower expanded disability status scale odds ratio 069 95 confidence interval ci 05097 p 0034 higher multiple sclerosis functional composite value 137 95ci 10518 p 0022 lower timed 25foot walk test 076 95 ci 06098 p 0033 lower 9hole peg test dominant hand 092 95 ci 086099 p 0029 fr group show significant improvement motor performance compared pr groupconclusion current analysis shows ms patients cognitive deficit greatest improvement sdmt provided da observed patients milder motor impairment cognitive motor responses treatments relatedtrial registration eu clinical trials register id 201300255864 https wwwclinicaltrialsregistereu ctrsearch searchquery201300255864 pmid34035835 pmcpmc8072854 doi101177 17562864211011286,0.0
fingolimod potentiates antifungal activity amphotericin b front cell infect microbiol 2021 apr 23 11627917 doi 103389 fcimb2021627917 ecollection 2021abstractcandida albicans c albicans opportunistic human fungal pathogen can cause severe infection clinic incidence mortality rate increasing rapidly amphotericin b amb clinical golden standard antifungal agent severe side effects limit clinical application thus lowering concentration increasing efficacy amb combinatorial antifungal therapy pursued industry academia identify fingolimod fty720 immunomodulatory drug used oral treatment relapsingremitting multiple sclerosis can potentiate efficacy amb c albicans growth synergistically furthermore observe antifungal efficacy fty720 combination amb diverse fungal pathogens intriguingly cells treated drugs hypersensitive endothelial endocytosis macrophage killing later found due hyperaccumulation reactive oxygen species corresponding increase activities superoxide dismutase catalase cells received combinatorial treatment therefore combination amb fty720 provides promising antifungal strategypmid33968796 pmcpmc8102868 doi103389 fcimb2021627917,0.0
cannabidiol oxidation product hu331 potential anticancer cannabinoidquinone narrative review abstractcannabidiol related cannabinoids exploration treatment number disease states cannabinoidquinone hu331 studied potential anticancer therapeutic previous studies provide evidence hu331 displays anticancer activity without known adverse events associated traditional anticancer agents brief review will explore literature related activity hu331 purified systems cancer cell lines animal models example hu331 displays inhibitory activity human topoisomerase ii known anticancer drug target multiple cell model systems ic50 value hu331 less 10 m addition mouse model systems demonstrate ability hu331 shrink tumors without causing cardiotoxicity addition will briefly review activity key analogs derivatives hu331 various disease states taken together published studies support exploration hu331 treatment cancer possibly disease states,0.0
foxp1 syndrome review literature practice parameters medical assessment monitoring abstractfoxp1 syndrome neurodevelopmental disorder caused mutations deletions disrupt forkhead box protein 1 foxp1 gene encodes transcription factor important early development many organ systems including brain numerous clinical studies elucidated role foxp1 neurodevelopment characterized phenotype foxp1 syndrome associated intellectual disability language deficits autism spectrum disorder hypotonia congenital anomalies including mild dysmorphic features brain cardiac urogenital abnormalities present review human studies summarizing clinical features individuals foxp1 syndrome enlist multidisciplinary group clinicians pediatrics genetics psychiatry neurology cardiology endocrinology nephrology psychology provide recommendations assessment foxp1 syndrome,0.0
vivo profiling natural alkaloid anatabine rodents pharmacokinetics antiinflammatory efficacy j nat prod 2021 mar 11 doi 101021 acsjnatprod0c01044 online ahead printabstractnatural alkaloids large class plantderived substances attracted considerable interest pharmacological activities study vivo pharmacokinetics antiinflammatory profile anatabine naturally occurring alkaloid characterized rodents anatabine found bioavailable brainpenetrant following systemic administration following intraperitoneal ip administration 1 2 5 mg kg anatabine caused dosedependent reduction carrageenaninduced paw edema rats mice inhibited production proinflammatory cytokines simultaneously elevated levels antiinflammatory cytokine dosedependent manner 2 h lipopolysaccharide challenge furthermore anatabine 10 20 mg kg day 4 weeks inhalation exposure effects murine model multiple sclerosis reducing neurological deficits bodyweight loss comparative studies pharmacokinetics antiinflammatory activity anatabine demonstrated bioequivalence rats following ip administration inhalation exposure study provides first detailed profile anatabine pharmacokinetics rodents also comprehensively characterizes antiinflammatory activities anatabine acute chronic inflammatory models findings provide basis characterizing optimizing antiinflammatory properties anatabinepmid33706515 doi101021 acsjnatprod0c01044,0.0
priming myelinspecific t cells absence dendritic cells results accelerated development experimental autoimmune encephalomyelitis plos one 2021 apr 23 16 4 e0250340 doi 101371 journalpone0250340 ecollection 2021abstractexperimental autoimmune encephalomyelitis eae established animal model multiple sclerosis ms inflammatory cd4+ t cell responses directed cns antigens including myelin proteolipid protein plp key mediators eae dendritic cells dcs critical induction t cell responses infectious agents however importance dcs priming selfreactive cd4+ t cells autoimmune disease ms unclear determine requirement dcs plpspecific cd4+ t cell responses eae genetically deleted cd11c+ dcs plp t cell receptor tcr transgenic sjl mice constitutively dc deficiency impair development selection pathogenic function plpspecific cd4+ t cells mice resulted accelerated spontaneous eae compared dc sufficient controls addition using genetic approach ablate dcs conditionally sjl mice show cd11c+ dcs dispensable presenting exogenous endogenous myelin antigen plpspecific t cells promoting proinflammatory t cell responses severe eae findings demonstrate constitutive conditional ablation cd11c+ dcs diminished selftolerance plp autoantigen show absence dcs nondcs can efficiently present cns myelin antigens plp selfreactive t cells resulting accelerated onset spontaneous induced eaepmid33891644 doi101371 journalpone0250340,1.0
combined epigenetic genetic study identified als age onset modifier abstractage onset amyotrophic lateral sclerosis als highly variable eg 2774 years carriers g4c2expansion c9orf72 might influenced environmental genetic factors via modulation dna methylation dnam cpgsites hence combined epigenetic genetic approach test hypothesis common single nucleotide polymorphisms snps cpgsites cpgsnps modify als age onset genomewide dnam analysis suggested three cpgsnps whose dnam levels significantly associated age onset 249 als patients q 005 next genetic analysis validated association rs4970944 age onset discovery n 469 p 0025 replication n 4160 p 0007 als cohorts metaanalysis cohorts combined showed median onset aacarriers two years later ggcarriers n 4629 p 00012 similar association observed tagging snps implicating 16 kb region 1q213 locus modifier als age onset notably rs4970944 genotypes also associated age onset c9orf72carriers n 333 p 0025 suggesting aallele delays onset 16 years analysis genotypetissue expression data revealed protective aallele linked reduced expression ctss cerebellum p 000018 critical brain region distributed neural circuits subserving motor control ctss encodes cathepsin s protein playing key role antigen presentation conclusion identified 16 kb locus tagged rs4970944 modifier als age onset findings support role antigen presenting processes modulating age onset als suggest potential drug targets eg ctss future replication studies encouraged validate link locus tagged rs4970944 age onset independent als cohorts including different ethnic groups,0.0
barcoded viral tracing singlecell interactions central nervous system inflammation science 2021 apr 23 372 6540 eabf1230 doi 101126 scienceabf1230abstractcellcell interactions control physiology pathology central nervous system cns study astrocyte cell interactions vivo developed rabies barcode interaction detection followed sequencing rabidseq combines barcoded viral tracing singlecell rna sequencing scrnaseq using rabidseq identified axon guidance molecules candidate mediators microgliaastrocyte interactions promote cns pathology experimental autoimmune encephalomyelitis eae potentially multiple sclerosis ms vivo cellspecific genetic perturbation eae studies vitro systems analysis ms scrnaseq datasets cns tissue established sema4d ephrinb3 expressed microglia control astrocyte responses via plexinb2 ephb3 respectively furthermore cnspenetrant ephb3 inhibitor suppressed astrocyte microglia proinflammatory responses ameliorated eae summary rabidseq identified microgliaastrocyte interactions candidate therapeutic targetspmid33888612 doi101126 scienceabf1230,0.0
cardiovascular organ damage clinical subtypes systemic sclerosis arterial stiffness echocardiography might ideal tools patient risk stratification cardiol res pract 2021 apr 23 20217915890 doi 101155 2021 7915890 ecollection 2021abstractbackground vascular damage recognized diagnostic landmark systemic sclerosis ssc limited diffuse subtypes early detection subclinical stage transthoracic echocardiography tte carotid femoral pulse wave velocity cfpwv may helpful therapeutic planning management aim study aim study evaluate presence subclinical cardiovascular damage patients limited diffuse ssc comparison cohort healthy individualsmethods consecutive patients limited diffuse ssc underwent complete tte cfpwv complete review clinical data controls 23 healthy subjects similar hemodynamic profiles selectedresults 41 patients 35 female aged 569 years 21 diffuse 20 limited ssc recruited past medical history cardiovascular risk factors gender distribution disease duration similar two groups well tte parameters hemodynamic indexescfpwv 65 668 vs 70 6285 p024 augmentation index 1456 142 vs 149 206 p052 patients limited ssc 10 years older patients diffuse ssc multiple regression analysis age p00154 disease duration p00467 resulted significant determinant cfpwv compared healthy controls significant difference emerged tte hemodynamic indexesconclusion ssc cfpwv increases age additional impact pathology subtype vascular damage ssc population accurately reflected increased arterial stiffness evaluated cfpwv classically defined echocardiographic findings organ damage ie left ventricular concentric remodelling increased filling pressures pmid33976934 pmcpmc8087482 doi101155 2021 7915890,0.0
decreased abundance akkermansia adrenocorticotropic hormone therapy patients west syndrome background infants suffer severe epileptic encephalopathy known west syndrome ws treatment adrenocorticotropic hormone acth indicates involvement gutbrain axis ws several pieces evidence show communication gut microbiota gm brain via hypothalamicpituitaryadrenal axis hpa axis blood cytokines study aimed 1 determining gm diversity infants ws 2 comparing results infants ws healthy infants also patients ws acth therapyresultsin study 29 infants ws 29 healthy infants aged 313 months recruited fecal samples collected dna extracted sequenced illumina miseq platform kruskalwallis ranksum test used analyze betweengroup differences chao1 index shannon index abundances gm different taxonomy levels r software used plot graphs top five dominant gm genera patients ws healthy infants showed significant differences however relative abundance genus akkermansia observed significantly p 0011 higher bt group hc group group 2 weeks acth therapy relative abundance akkermansia significantly p 0003 decreasedconclusionthe relative abundance akkermansia observed significantly higher patients ws healthy infants however relationship akkermansia ws pathogenesis needs clarified studies,0.0
results three gamma knife radiosurgery procedures recurrent trigeminal neuralgia j neurosurg 2021 apr 23 135 6 17891798 doi 103171 202010jns202323abstractobjective gamma knife radiosurgery gkrs established surgical option treatment trigeminal neuralgia tn particularly highrisk surgical candidates recurrent pain however outcomes three gkrs treatments rarely reported herein authors reviewed outcomes among patients undergone three gkrs procedures recurrent tnmethods authors conducted multicenter retrospective analysis patients undergone least three gkrs treatments tn july 1997 april 2019 two different institutions clinical characteristics radiosurgical dosimetry technique pain outcomes complications reviewed pain outcomes scored barrow neurological institute bni scale including time pain relief bni score iii recurrence bni score iii results total 30 patients identified including 16 women 14 men median pain duration prior first gkrs treatment 10 years three patients 10 multiple sclerosis time pain relief longer third treatment p 00003 whereas time pain recurrence similar across successive treatments p 0842 complete partial pain relief achieved 931 patients third treatment maximum pain relief achieved third treatment significantly better among patients prior percutaneous procedures p 00111 patients shorter durations pain initiation gkrs therapy p 00449 new progressive facial sensory dysfunction occurred 29 patients third gkrs treatment reported bothersome 14 one patient developed facial twitching another experienced persistent lacrimation statistically significant predictors adverse effects following third treatment found median 39 months followup 77 patients maintained complete partial pain relief three patients underwent fourth gkrs treatment including one ultimately received five treatments reported sustained pain relief extended followupconclusions authors describe largest series date patients undergoing three gkrs treatments refractory tn third treatment may produce outcomes similar first two treatments terms longterm pain relief recurrence adverse effectspmid34852325 doi103171 202010jns202323,0.0
enhanced detection expanded repeat mrna foci hybridization chain reaction abstracttranscribed nucleotide repeat expansions form detectable rna foci patient cells contribute disease pathogenesis widely used method detecting rna foci fluorescence situ hybridization fish powerful can suffer issues related signal background developed repeatspecific form hybridization chain reaction rhcr alternative method detection repeat rna foci two neurodegenerative disorders c9orf72 associated als frontotemporal dementia c9 als ftd fragile xassociated tremor ataxia syndrome rhcr g4c2 cgg repeats exhibited comparable specificity 40 sensitivity compared fish better detection nuclear cytoplasmic foci human c9 als ftd fibroblasts patient ipsc derived neurons patient brain samples using rhcr observed integrated stress response isr activation significantly increased number endogenous g4c2 repeat rna foci triggered selective nuclear accumulation without evidence stress granule colocalization patient fibroblasts patient derived neurons data suggest rhcr can useful tool tracking behavior repeat expansion mrna c9 als ftd repeat expansion disorders,0.0
japanese rate severity different diseases injuriesan assessment disability weights 231 health states 37 318 japanese respondents background disability weights dws weight factors reflect severity health states estimates disabilityadjusted life years new set global dws published global burden diseases injuries gbd 2013 study relied sampling various world regions included little data countries east asia study aimed measure dws japan using comparable methods compare results previous estimates gbd 2013 dw studymethodswe conducted webbased survey 2019 estimate dws 231 health states japanese population survey included five new health states otherwise followed method gbd dw measurement study survey consisted 15 paired comparison pc questions 3 population health equivalence questions phe per respondent analyzed pc data using probit regression rescaled results dw units 0 equivalent full health 1 equivalent death findingswe considered 37 318 nationally representative respondents values resulting dws ranged 0707 95 uncertainty interval ui 05270842 spinal cord injury neck level untreated 0004 ui 00010009 mild anemia high correlation japanese dw gbd 2013 dw observed considerable disagreement 226 comparable health states 55 243 showed factoroftwo difference 41 746 higher value japanese dw many health states higher dw japan study injuries including amputation fracture hearing vision loss mental behavioral substance use disorders generally tended lowerconclusionsthis study created empirical basis assessment japanese dws health status findings study based japanese population suggest might contextual differences rating severity health states compared previous surveys conducted elsewhere,0.0
chondroblastoma patella secondary aneurysmal bone cyst easily misdiagnosed bone tumora case report literature review background chondroblastoma cb rare primary benign bone tumor commonly affects men aged 1520 years usually detected epiphysis long bones proximal femur humerus tibia patella infrequent site cb secondary aneurysmal bone cyst abc extremely rare patella can easily confused common bone tumors patella thus necessary make right diagnosis get good outcomecase presentationwe presented case 30yearold man suffering anterior knee pain past 6 months aggravated 2 weeks presentation osteolytic bone destruction patella detected xray computed tomography ct examinations magnetic resonance imaging mri detected fluid level accordingly secondary abc presumed diagnosed condition giant cell tumor gct secondary abc accordingly performed curettage inside focus region autogenous bone grafting following patients medical history physical manifestations results physical ancillary examinations disease characteristics however intraoperative postoperative outcomes indicated patients histopathology consistent typical cb suggesting definitive error diagnosis accordingly patient finally diagnosed patella cb along secondary abcconclusionspast studies demonstrated 3 commonest bone tumors affecting patella gct cb abc cb secondary abc can easily misdiagnosed gct secondary abc abc performing incision biopsy excision biopsy conducting histological examination may effective method suspected cb secondary abc,0.0
efficacy safety alemtuzumab 6 years final results 4year carems extension trial ther adv neurol disord 2021 apr 23 141756286420982134 doi 101177 1756286420982134 ecollection 2021abstractbackground 2year carems ii trials alemtuzumab 12 mg administered 5 consecutive days core study baseline 3 consecutive days 12 months later significantly improved outcomes versus subcutaneous interferon beta1a sc ifnb1a relapsingremitting multiple sclerosis patients present final 6year carems extension trial results camms03409 compare outcomes 6 years patients randomized treatment groups core study baselinemethods 4year extension alemtuzumab patients alemtuzumabonly received asneeded additional alemtuzumab 12 months apart disease activity course 2 sc ifnb1a patients entered extension discontinued sc ifnb1a received 2 alemtuzumab 12 mg courses ifnalemtuzumab followed additional asneeded alemtuzumabresults year 6 63 carems 50 carems ii alemtuzumabonly patients received neither additional alemtuzumab diseasemodifying therapy lasting suppression disease activity improved disability slowing brain volume loss bvl carems patients treatmentnaive less disability shorter disease duration disease activity bvl significantly reduced ifnalemtuzumab patients similar alemtuzumabonly patients year 6 among carems ii patients inadequate response prior treatment disability longer disease duration alemtuzumab significantly improved clinical magnetic resonance imaging outcomes including bvl ifnalemtuzumab patients however disability outcomes less favorable versus alemtuzumabonly patients safety profiles including infections autoimmunities following alemtuzumab similar treatment groupsconclusion study demonstrates high efficacy alemtuzumab 6 years similar safety profile treatment groupsclinicaltrialsgov identifiers nct00530348 nct00548405 nct00930553pmid34035833 pmcpmc8072102 doi101177 1756286420982134,0.0
research trends hotspots healthrelated quality life bibliometric analysis 2000 2019 background number research articles healthrelated quality life hrqol strikingly increasing study aimed explore general trends hotspots hrqolmethodsbased web science database research hrqol published 2000 2019 identified bibliometric analysis performed based number articles citations published journals authors addresses keywords descriptive analysis visualization geographic distribution keyword clustering analysis applied collected dataresultsthe annual number articles showed growth past twenty years annual total citations annual citations per article decreasing trends articles hrqol likely published journals multisubject categories hrqol research mainly distributed across north america europe throughout twenty years ushered vigorous development worldwide 2015 cooperation strength domestic institutions much greater international institutions hrqol research six concentrated clusters hrqol depression obesity disability oncology fatigueconclusionthis study provided overall perspective global research trends hotspots hrqol potential insight future research hrqol research experienced significant increasing development 20002019 especially hrqol measurement instruments however significant regional disparities scientific output hrqol,0.0
mild traumatic brain injury induces microvascular injury accelerates alzheimerlike pathogenesis mice abstractintroductiontraumatic brain injury tbi considered robust environmental risk factor alzheimers disease ad besides direct neuronal injury neuroinflammation vascular impairment also hallmark event pathological cascade tbi however vascular connection tbi subsequent ad pathogenesis remains underexploredmethodsin closedhead mild tbi mtbi model mice controlled cortical impact examined time courses microvascular injury bloodbrain barrier bbb dysfunction gliosis motor function impairment wild type c57bl 6 mice also evaluated bbb integrity amyloid pathology well cognitive functions mtbi 5xfad mouse model adresultsmtbi induced microvascular injury bbb breakdown pericyte loss basement membrane alteration cerebral blood flow reduction mice bbb breakdown preceded gliosis importantly mtbi accelerated bbb leakage amyloid pathology cognitive impairment 5xfad micediscussionour data demonstrated microvascular injury plays key role pathogenesis ad mtbi therefore restoring vascular functions might beneficial patients mtbi potentially reduce risk developing ad,0.0
case report antibodies nmethyldaspartate receptor patient multiple sclerosis front immunol 2021 apr 23 12664364 doi 103389 fimmu2021664364 ecollection 2021abstractthe association multiple sclerosis antinmethyldaspartate receptor encephalitis limited merely case reports exploration pathogenic mechanisms underlying overlap two disease entities limited therefore case reports literature review nmethyldaspartate receptor antibody patients multiple sclerosis unusual noteworthy young female first episode paresthesia motor symptoms positive antinmethyldaspartate receptor antibody recovered immunotherapy first relapse patient developed disorders consciousness positive antinmethyldaspartate receptor antibody findings magnetic resonance imaging showed features autoimmune encephalitis also controlled immunotherapy second relapse antinmethyldaspartate receptor antibody turned negative oligoclonal bands presented positive findings magnetic resonance imaging showed features multiple sclerosis afterwards followed patient receiving disease modifying treatment monitor efficacy safety teriflunomide based literature review demyelinating diseases patients antineuronal antibody complex diverse atypical symptoms therefore high attention increased alertness necessary neurologists conclusively antineuronal antibody may present many neuroinflammatory conditions diagnostic criteria used caution clinical presentation atypical neurologists rely excessively laboratory tests diagnose neurological diseases timely comprehensive examination consideration well early standardized treatment key factors reduce patient recurrence obtain good prognosispmid33968065 pmcpmc8102820 doi103389 fimmu2021664364,1.0
3dfast gray matter acquisition phase sensitive inversion recovery magnetic resonance imaging 3 tesla application detection spinal cord lesions patients multiple sclerosis plos one 2021 apr 22 16 4 e0247813 doi 101371 journalpone0247813 ecollection 2021abstractbackground purpose compare 3dfast gray matter acquisition phase sensitive inversion recovery 3dfgapsir conventional 3dshorttau inversion recovery 3dstir sagittal t1and t2weighted mri dataset 3 tesla detecting ms spinal cord lesionsmaterial methods prospective singlecenter study approved institutional review board enrolled participants december 2016 august 2018 two neuroradiologists blinded data individually analyzed 3dfgapsir conventional datasets separately random order discrepancies resolved consensus third neuroradiologist primary judgment criterion number ms spinal cord lesions secondary judgment criteria included lesion enhancement lesion delineation readerreported confidence lesiontocordcontrastratio wilcoxons test used compare two datasetsresults 51 participants included 3dfgapsir detected significantly lesions conventional dataset 344 versus 171 respectively p0001 two participants detected lesion conventional dataset whereas 3dfgapsir detected least one lesion 3 51 participants single enhancing lesion detected datasets lesion delineation readerreported confidence significantly higher 3dfgapsir 45 iqr 1 versus 2 iqr 05 p00001 45 iqr 1 versus 25 iqr 05 p00001 lesiontocordcontrastratio significantly higher using 3dfgapsir opposed 3dstir t2 14 iqr 0 3 versus 04 iqr 0 1 03 iqr 0 1 p 004 correlations clinical data inter intraobserver agreements higher 3dfgapsirconclusion 3dfgapsir improved overall ms spinal cord lesion detection compared conventional set detected enhancing lesionspmid33886586 doi101371 journalpone0247813,0.0
immersive virtual reality gait rehabilitation increases walking speed motivation usability evaluation healthy participants patients multiple sclerosis stroke background rehabilitation gait disorders patients multiple sclerosis ms stroke often based conventional treadmill training virtual reality vr based treadmill training can increase motivation improve therapy outcomes present study evaluated immersive virtual reality application using headmounted display hmd gait rehabilitation patients 1 demonstrate feasibility acceptance 2 compare shortterm effects semiimmersive presentation using monitor conventional treadmill training without vr assess usability systems estimate effects walking speed motivationmethodsin withinsubjects study design 36 healthy participants 14 persons ms stroke participated three experimental conditions vr via hmd vr via monitor treadmill training without vr resultsfor groups walking speed hmd condition higher treadmill training without vr monitor condition healthy participants reported higher motivation hmd condition compared conditions importantly side effects sense simulator sickness occurred usability ratings high increases heart rate observed following vr conditions presence ratings higher hmd condition compared monitor condition user groups healthy study participants 89 patients 71 preferred hmdbased training among three conditions patients imagine using frequentlyconclusionsfor first time present study evaluated usability immersive vr system gait rehabilitation direct comparison semiimmersive system conventional training without vr healthy participants patients study demonstrated feasibility combining treadmill training immersive vr due high usability low side effects might particularly suited patients improve training motivation training outcome e g walking speed compared treadmill training using semiimmersive vr immersive vr systems still require specific technical setup procedures taken account specific clinical usecases costbenefit assessment,0.0
result cementless total hip arthroplasty patient osteopoikilosis hip dysplasia advanced osteoarthritis case report background osteopoikilosis opk rare benign sclerosing bone dysplasia often incidentally found plain radiography opk generally require treatment nevertheless osteonecrosis degenerative joint disease can occur setting opk little known regard longevity arthroplasty prostheses implanted opkbearing bonescase presentationa 55yearold male presented progressive right hip pain 2012 diagnosed coexisting osteopoikilosis developmental dysplasia right hip advanced osteoarthritis series imaging studies including radiographs magnetic resonance imaging mri bone scan cementless total hip arthroplasty performed treat right hip pain radiographs eightyear followup showed prosthetic components wellfixed harris hip score patients right hip 93 patient can walk without assistance work construction workerconclusioncementless arthroplasty can considered patients hip arthropathies coexisting osteopoikilosis continued followup required establish longterm results,0.0
applications brain organoids neurodevelopment neurological diseases abstracta brain organoid selforganizing threedimensional tissue derived human embryonic stem cells pluripotent stem cells able simulate architecture functionality human brain brain organoid generation methods abundant continue improve now vivo vascularized brain organoid encouragingly reported combination brain organoids immunestaining singlecell sequencing technology facilitates understanding brain organoids including structural organization diversity cell types recent publications reported brain organoids can mimic dynamic spatiotemporal process early brain development model various human brain disorders serve effective preclinical platform test guide personalized treatment review introduce current state brain organoid differentiation strategies summarize current progress applications medical domain discuss challenges prospects promising technology,0.0
humoral immune response covid19 mrna vaccine patients multiple sclerosis treated highefficacy diseasemodifying therapies ther adv neurol disord 2021 apr 22 1417562864211012835 doi 101177 17562864211012835 ecollection 2021abstractbackground aims national multiple sclerosis society expert organizations recommended patients multiple sclerosis ms vaccinated covid19 however effect diseasemodifying therapies dmts efficacy mount appropriate immune response unknown aimed characterize humoral immunity mrnacovid19 ms vaccinees treated highefficacy dmtsmethods measured sarscov2 igg response using antispike proteinbased serology euroimmun 125 ms patients vaccinated bnt162b2covid19 vaccine 1 month second dose patients either untreated treatment fingolimod cladribine ocrelizumab group healthy subjects similarly vaccinated served control percent subjects developed protective antibodies titer time last dosing evaluatedresults protective humoral immunity 979 100 100 227 38 observed covid19 vaccinated healthy subjects n 47 untreated ms patients n 32 ms patients treated cladribine n 23 ocrelizumab n 44 fingolimod n 26 respectively sarscov2 igg antibody titer high healthy subjects untreated ms patients ms patients cladribine treatment within 29555 days second vaccine dose 227 patients treated ocrelizumab developed humoral igg response irrespective normal absolute lymphocyte count fingolimodtreated ms patients low lymphocyte count failed develop sarscov2 antibodies age disease duration time last dosing affect humoral response covid19 vaccinationconclusions cladribine treatment impair humoral response covid19 vaccination recommend postponing ocrelizumab treatment ms patients willing vaccinated protective humoral response can expected recommend vaccinating ms patients treated fingolimod protective humoral response expectedpmid34035836 pmcpmc8072850 doi101177 17562864211012835,0.0
gut microbiota immunoglobulin nephropathy malaysian perspective abstractintroductionthe alteration gut microbiome gutkidney axis associated proinflammatory state chronic kidney disease ckd smallscaled italian study shown association gut microbiome immunoglobulin nephropathy igan however data gut microbiota igan asian population study compares gut microbial abundance diversity healthy volunteers malaysian igan cohortmethodsa comparative crosssectional study conducted involving biopsyproven igan patients clinical remission matched controls malaysian tertiary centre demographic data routine blood urine results recorded stool samples collected dna extracted 16s rrna gene sequencing profile gut microbiotaresultsthirtysix igan patients 13 male 23 female mean age 455 134 years median estimated glomerular filtration rate egfr 790 621922 mls min 173m2 median remission 7 years analysed compared 12 healthy controls 4 male 8 female mean age 465 135 years egfr 865 742937 mls min 173m2 demographic laboratory parameters gender ethnicity body mass index bmi haemoglobin serum urea serum albumin comparable two groups significant differences seen operational taxonomic unit otu alpha diversity shannon index igan healthy controls alpha diversity increased increasing ckd stage p 0025 firmicutes bacteroidetes f b ratio low igan healthy cohort fusobacteria phylum significantly increased p 0005 whereas euryarchaoeota phylum reduced p 0016 igan group compared control cohortconclusionalthough found differences otu alpha diversity igan remission control cohort differences two groups phylum level,0.0
multicenter interventional phase iv study assessment effects patient#39 s satisfaction peg ifn beta1a prefilled pen subjects relapsingremitting multiple sclerosis unsatisfied injectable subcutaneous interferons platinum study front neurol 2021 apr 22 12637615 doi 103389 fneur2021637615 ecollection 2021abstractsubcutaneous sc interferons beta ifnbeta effective therapies treatment relapsingremitting multiple sclerosis rrms factors dosing schedule needle intolerance fatigue side effects may impact patient satisfaction treatment improvement patient satisfaction may increase adherence treatment patient quality life study aimed evaluating impact switching peginterferon beta1a pegifn beta1a patients rrms unsatisfied sc interferons multicenter openlabel phase iv platinum study conducted 32 italian centers primary endpoint changes baseline score convenience satisfaction domain tsqm9 questionnaire 12 weeks secondary endpoints patients global satisfaction shortterm adherence treatment satisfaction injection system effect fatigue disease activity patient inability score total 193 patients enrolled 166 86 completed study receiving pegifn beta1a 24 weeks patients switching pegifn beta1a sc interferons reported significant improvement p 0001 convenience score scores tsqm9 questionnaire 12 24 weeks p 0001 peg ifn beta1a attained high adherence treatment 92 86 12 24 weeks respectively stable annualized relapse rate arr 24 weeks 94 participants relapse free adverse events aes recorded 82 patients 42 mild moderate common ae flulike syndrome 292 patients switching sc ifn beta therapy peg ifn beta1a showed high treatment satisfaction positive safety profile comparable currently approved firstline injectable sc interferons study suggests peg ifn beta1a might represent treatment choice improve adherence rrms patients unsatisfied sc interferonspmid33967938 pmcpmc8101263 doi103389 fneur2021637615,0.0
partners leaky gut syndrome intestinal dysbiosis autoimmunity front immunol 2021 apr 22 12673708 doi 103389 fimmu2021673708 ecollection 2021abstractthe intestinal surface constitutively exposed diverse antigens food antigens foodborne pathogens commensal microbes intestinal epithelial cells developed unique barrier functions prevent translocation potentially hostile antigens body disruption epithelial barrier increases intestinal permeability resulting leaky gut syndrome lgs clinical reports suggested lgs contributes autoimmune diseases type 1 diabetes multiple sclerosis rheumatoid arthritis celiac disease furthermore gut commensal microbiota plays critical role regulating host immunity abnormalities microbial community known dysbiosis observed patients autoimmune diseases however pathological links among intestinal dysbiosis lgs autoimmune diseases fully elucidated review discusses current understanding commensal microbiota contributes pathogenesis autoimmune diseases modifying epithelial barrierpmid33968085 pmcpmc8100306 doi103389 fimmu2021673708,0.0
effects metabolic memory inflammation fibrosis associated diabetic kidney disease epigenetic perspective abstractdiabetic kidney disease dkd one common microvascular complication type 1 t1dm type 2 diabetes mellitus t2dm leading cause endstage renal disease esrd worldwide persistent inflammation subsequent chronic fibrosis major causes loss renal function associated progression dkd esrd fact dkd progression affected combination genetic environmental factors approximately onethird diabetic patients progress develop dkd despite intensive glycemic control propose essential concept metabolic memory epigenetic modifications extensively studied mechanism metabolic memory shown contribute susceptibility develop dkd epigenetic modifications also play regulatory role interactions genes environmental factors epigenetic contributions processes inflammation fibrogenesis involved dkd occur different regulatory levels including dna methylation histone modification noncoding rna modulation compared genetic factors epigenetics represents new therapeutic frontier understanding development dkd may lead therapeutic breakthroughs due possibility reverse modifications therapeutically early recognition epigenetic events biomarkers crucial timely diagnosis intervention dkd prevention progression dkd esrd herein will review latest epigenetic mechanisms involved renal pathology type 1 t1dn type 2 diabetic nephropathy t2dn highlight emerging role possible therapeutic strategies based understanding role epigenetics dkdassociated inflammation fibrogenesis,0.0
economic gradient onset disability india background disability india associated increasing noncommunicable diseases rising longevity increasing accidents injuries though studies examined prevalence patterns socioeconomic correlates disability attempt made estimating age onset disability indiaobjectivethis paper investigates economic gradient age onset locomotor visual hearing speech mental retardation mental illness disabilities indiamethodwe use nationally representative data 106 894 disabled individuals 76th round national sample survey nss 2018 descriptive statistics kernel density kaplanmeier survival curves linear regression models used analysisresultthe disability rate india 2184 per 100 000 persons disability rate highest locomotor 1353 followed hearing 296 visual 234 speech 228 mental retardation 158 mental illness 131 85 mental retardation 80 speech disabilities occur birth 82 locomotor 81 visual disabilities occur birth among disability birth median age mental retardation 2 years followed mental illness 28 years speech 29 years locomotor 42 years visual 55 years 56 years hearing disability adjusting socioeconomic covariates age onset locomotor speech disabilities among poorest individuals 7 11 years earlier richest respectivelyconclusionthe economic gradient onset locomotive speech disabilities strong age onset disability earliest mental retardation followed mental illness speech disability,0.0
ms can considered primary progressive disease cases patients superimposed relapses yes multiple sclerosis ms patients escape progressive course survive long enough majority cases progression supervenes variable latency onset relapsing remitting phase clinical boundaries relapsing progressive course often indistinct surrogate markers universally accepted definition continuous unremitting disability accumulation defining clinical phenotypes ms can challenging even experienced clinicians current phenotypical distinction relapsing remitting rr secondary progressive sp primary progressive pp ms provides standardized terminology enhances homogeneity clinical trials however despite variable patterns evolution biological reasons discerning different phenotypes pathological mechanisms underlying acute attacks progression known tightly intermingled occur concomitantly since early phase disease irrespective clinical symptoms wide spectrum central nervous system tissue alterations seen across stages quantitative rather qualitative differences1 pp sp ms share similar pathological features respect extent inflammatory infiltrates axonal damage cortical demyelination1 epidemiological data corroborate unifying disease model ms predominantly agerelated clinical phenotypes growing older risk experiencing progressive course proportionally increases relapses gradually become sparse infrequent2 progressive ms patients without preceding rr course accumulate disability similar rate share strikingly similar mean age onset progression indicating ppms preceded asymptomatic rr phase3 consistent view subjects radiologically isolated syndrome can develop pp course years incidental detection white matter abnormalities confirming protracted preprogressive prodrome subclinical disease activity similar rrms4 despite biologically active progressive ms can remain clinically undetectable years clinicians reluctant document progressive accumulation disability unrelated clinical attacks early stage rr phase based recently proposed objective definition spms attainment least expanded disability status scale edss 4 required mark transition progressive phase5 however clinical progression can uncovered early phase disease among patients permanent motor impairment especially relapses poor recovery can potentially cloud progressive accumulation disability uncommon highlighted george ebers group addressing clinical course single attack progressive ms rare phenotype distinguished single demyelinating episode onset followed years later progressive phase lack ongoing relapses subgroup progression mostly presented clinically exerciseinduced ambulation worsening pinpointed 8 mean years onset average edss 2 therefore much earlier classic spms cases6 line early intuitive observations recent data indicate continuous progression independent relapsing activity pira commonly observed rr phase pooled analysis two opera trials demonstrated interferon ocrelizumab groups relatively short disease duration mean 6years low baseline mean edss score 28 impressively large proportion patients 78 87 respectively accumulating disability unrelated inflammatory attacks mostly secondary worsening walking impairment7 provides clinical evidence early underlying progressive course despite effective therapeutic relapse suppression caution using lack ongoing focal inflammation marker disease stability adequate control inflammatory parameters might provide sense false security continuous smouldering process underpins subtle clinical deterioration stands important unmet treatment target changes whole brain grey matter volume 7 accumulation chronic slowing expanding lesions8 microglia activation normal appearing white matter perilesional areas 9 plausible drivers pira events rr phase focal inflammatory activity dominant clinical feature albeit representing tip pathological iceberg observations challenge dichotomy relapsing progressive disease supporting one stage disorder model ms patients exhibit progressive course since disease onset can overlapped relapses detrimental processes spanning across disease stages underpinning progressive accumulation disability start early subtly emerge clinically strong influence agerelated biological changes induce immune senescence exhaustion compensatory mechanisms10 individual immune system proactivity accounts simultaneous highly variable superimposed relapsing activity overlaps progressive course additionally contributes disability accumulation wide spectrum agerelated clinical manifestations young patients likely experience relapse onset progressive ms display initial floridly inflammatory course gradually subsides growing older subclinical neurodegeneration becomes clinically evident opposite extreme lay older patients present pp course distinguished resistance clinical inflammatory activity possibly related undetermined immunological qualitative differences compared spms alike neurodegenerative disorders parkinson alzheimer diseases progressive ms preceded prodromal phase unknown duration meeting conventional clinical definition remains debated whether relapses represent concomitant epiphenomenon primary neuroaxonal loss potentially promotes release highly antigenic myelin fragments secondarily triggering innate adaptive immune responses insideout model contrast traditional outsidein view primary process starting periphery dysregulated immune reaction causing inflammatory response eventually lead axonal degeneration tight interconnection neurodegenerative inflammatory mechanisms makes two hypotheses equally likely leaving question unresolved however evidence early progressive accumulation disability independent relapses discloses dissociation therapeutic suppression inflammatory activity disease progression highlights need shifting treatments strategies target broadly pathological mechanisms driving ms specific focus halting smouldering processes account progressive worsening since early stage declaration conflicting interests author declared following potential conflicts interest respect research authorship publication article dr scalfari received honoraria participations advisory board conference attendances teva biogen novartis sanofigenzyme roche celgene fu,1.0
immune checkpoints novel class therapeutic targets autoimmune diseases front immunol 2021 apr 21 12645699 doi 103389 fimmu2021645699 ecollection 2021abstractautoimmune diseases multiple sclerosis type1 diabetes outcomes failure immune tolerance immune tolerance sustained interplays two interdependent clusters immune activities immune stimulation immune regulation mechanisms immune regulation exploited therapeutic targets treatment autoimmune diseases one mechanisms immune checkpoints icps roles icps maintaining immune tolerance hence suppressing autoimmunity revealed animal models validated clinical successes icptargeted therapeutics autoimmune diseases recently roles highlighted clinical discovery blockade icps causes autoimmune disorders given crucial roles icps immune tolerance plausible leverage icps group therapeutic targets restore immune tolerance treat autoimmune diseases review first summarize working mechanisms icps particularly utilized therapeutic development recount agents approaches developed target icps treat autoimmune disorders agents take forms fusion proteins antibodies nucleic acids cells also review discuss safety information therapeutics wrap review providing prospects development icptargeting therapeutics summary everincreasing studies results icptargeting therapeutics underscore tremendous potential become powerful class medicine autoimmune diseasespmid33968036 pmcpmc8097144 doi103389 fimmu2021645699,0.0
disability quality life productivity impairment employer costs migraine workplace background migraine leading cause days lost due disability world among people less 50 years age paucity evidence impact migraine headache disorders cost productivity losses workplacemethodsemployee population survey assessed prevalence characteristics disability headache disorders japanese information technology company study supported world health organization western pacific region office international headache societyresults2458 1963men 495 women 2494 responded survey utilized ichd3 beta criteria among 13 205 male 123 female migraine m 53 1093 male 207 female tensiontype headache tth 4 61 male 27 female migraine tth m tth number days productivity work reduced half headache significantly higher migraine compared tth normbased scoring sf12v2 significantly lower m tth m tth economic loss due absenteeism migraine calculated 2383us year person dayoff 902us year person halfday using migraine disability assessment score midas economic loss due presenteeism migraine calculated 3754us year person using midas 2217us year person using work productivity activity impairment questionnaire wpai furthermore estimated cost productivity loss associated presenteeism using wpai calculated 213 billion us year japan wholeconclusionsthis study revealed high prevalence disease burden among employees migraine associated substantial losses productivity employer cost results support development implementation workplace programs improve migraine management workplace reduce burden costs associated lost workplace productivity,0.0
assessment cognitive functions patients multiple sclerosis applying normative values raos brief repeatable battery portuguese population background brief repeatable battery neuropsychological tests brbnt one sensitive used measures detecting cognitive impairment multiple sclerosis ms objectivethe aim study adapt validate battery portuguese population ms patientsmethodsthe portuguese version brbnt applied stratified control national sample 326 individuals considering sex age educational level geographic location also clinical sample 115 ms patients several national hospitals exploration psychometrics properties portuguese brbnt norms producedresultsthe normative data presented regressionbased formula adjust test scores gender education age results reveal brbnt ability differentiate ms patients healthy participants cognitive performanceconclusionthis study demonstrated clinical population good ability detect cognitive impairment clearly contributed reinforcing neuropsychological assessment portugal patients ms providing new set instruments can used clinical practice future studies moreover will allow rigorous precise support relation neuropsychological assessment future longitudinal studies clinical trials,0.0
epigenomewide association study level change cognitive abilities midlife late life background epigenetic mechanisms important aging may involved latelife changes cognitive abilities conducted epigenomewide association study leukocyte dna methylation relation level change cognitive abilities midlife late life 535 swedish twins resultsmethylation levels measured infinium human methylation 450 k infinium methylationepic array sites passing quality control arrays selected analysis n 250 816 empirical bayes estimates individual intercept age 65 linear quadratic change obtained latent growth curve models cognitive traits used outcomes linear regression models significant sites p 24 107 followed betweenwithin twin pair models adjusting familial confounding fullgrowth modeling identified six significant associations dna methylation level cognitive abilities age 65 cg18064256 ppp1r13l processing speed spatial ability cg04549090 nrxn3 spatial ability cg09988380 pogz cg25651129 cg08011941 entpd8 working memory genes involved neuroinflammation neuropsychiatric disorders atp metabolism withinpair associations approximately half betweenpair associations across sites fullgrowth curve models associations dna methylation cognitive level age 65 small effect sizes associations dna methylation longitudinal change cognitive abilities small effect sizesconclusionsleukocyte dna methylation associated level change cognitive abilities associations substantially attenuated withinpair analyses indicating influenced part genetic factors,0.0
ms can considered primary progressive disease cases patients superimposed relapses primary progressive ms nomenclature indicates steadily progressive neurodegeneration perhaps punctuated periods quiescence overall relentless downhill course without improvements also implies steady loss axons within central nervous system cns frequently associated impairment ambulation reasons progressive axonal loss fully known likely multifactorial contend multiple sclerosis ms progressive beginning extrapolating stance argue people ms steady loss cns axons beyond occurs naturally aging association relapses side debate might argue progressive ms can obscured overlying relapses neuroplasticity base stance progressive ms present ms initiation people ms upon following pillars 1 clinical cases bona fide benign ms lasting decades 2 imaging evidence nonprogression persons ms although identifying benign ms requisite decades followup remains controversial benign ms undoubtedly exists1 argue benign ms exist substantial proportion people ms underlying progressive ms even accounting possible periods quiescence multiple sclerosis severity score based expanded disability status scale edss scores 9892 primarily european ms patients relation disease durations2 ms patients followed dedicated ms centers suggesting majority correct diagnosis ms average disease duration patients study 117years study included several hundred people 15 years duration ms 25 edss 25 less close normal neurological examination 200 people followed 20years even 20years disease duration 15 edss 25 lower proportions similar derived london ontario ms cohort 3 supporting veracity existence population ms patients longstanding minimally altered neurological examinations united states new york state ms consortium nysmsc reported retrospective study 6000 persons ms observed 198 nysmsc patients qualified benign4 conservative definition edss 2 10years duration since symptom onset adopted mean duration since symptom onset 17 67years argue difficult reconcile cases ms remain without significant disability accumulation 15 20years underlying progressive disease even accounting neuroplasticity may argue benign ms adequately capture types impairment due reliance edss ambulation particular edss sufficiently capture cognitive dysfunction recent study cognition benign ms found extensive battery 16 neuropsychological tests cognitive dysfunction identified 85 study suggests even taking account cognitive impairment proportion persons truly benign likely minimally reduced compared figures found canadian european us groups referenced imaging studies support progressive neurodegenerative changes patients ms subset patients minimal radiologic evidence progression based variety imaging techniques gray matter atrophy recognized particularly sensitive marker neurodegeneration6 yet 20years followup gray matter fraction benign ms different clinically isolated syndrome healthy subjects7 axonal damage measured proton magnetic resonance mr spectroscopy whole brain nacetylaspartate also different benign ms healthy controls8 progressive ms increased numbers cortical lesions detected special magnetic resonance imaging mri sequences mridetected cortical lesions frequently absent benign ms9 quantitative magnetization transfer imaging normal appearing white matter cerebral cortex shown similar values benign ms healthy controls10 ms typically considered disease two distinct phases early inflammation later degenerative however imaging pathologic studies confirmed notion oversimplification correlation inflammation neurodegeneration often apparent pathologic changes due can occur independently within different cns compartments compensatory reserve neuroplasticity central nervous system can sustain injury long symptoms signs become clinically apparent indeed processes underlying disease progression neurodegeneration may present varying degrees start many patients relapsing ms however numerous epidemiological imaging studies mentioned support ms primary progressive disorder superimposed relapses start people ms declaration conflicting interests author s declared following potential conflicts interest respect research authorship publication article ahc consulted biogen celgene emd serono genentech roche greenwich biosciences janssen pharmaceuticals novartis rtn consulted biogen celgene genentech genzyme lundbeck nervgen third rock ventures viela bio funding author s disclosed receipt following financial support research authorship publication article ahc supported manny rosalyn rosenthaldr john l trotter ms center chair neuroimmunology,0.0
mirnas alter t helper 17 cell fate pathogenesis autoimmune diseases front immunol 2021 apr 21 12593473 doi 103389 fimmu2021593473 ecollection 2021abstractt helper 17 th17 cells characterized secretion il17 cytokine essential immune response bacterial fungal infections despite beneficial roles th17 cells unrestrained il17 production can contribute immunopathology inflammatory autoimmune diseases including multiple sclerosis rheumatoid arthritis inflammatory bowel disease although diverse outcomes directed activation th17 cells regulation th17 cells incompletely understood discovery micrornas mirnas involved regulation th17 cell differentiation function greatly improved understanding th17 cells immune response disease provide overview biogenesis function mirna summarize role mirnas th17 cell differentiation function finally focus recent advances mirnamediated dysregulation th17 cell fate autoimmune diseasespmid33968012 pmcpmc8096907 doi103389 fimmu2021593473,0.0
effects illness perceptions healthrelated quality life patients rheumatoid arthritis china abstractobjectivesfor patients rheumatoid arthritis ra china little known illness perceptions affect healthrelated quality life hrqol present study investigated associations specific illness perceptions due ra hrqol featuresmethodsfor 191 patients ra illness perceptions measured using brief illness perceptions questionnaire bipq comprising 8 domains hrqol determined medical outcomes study 36item shortform health survey sf36 multivariate linear regression analyses performedresultsthe overall bipq patients ra 4909 1106 highest lowest scores concern 915 181 personal control 430 252 respectively multivariate stepwise regression analyses showed overall bipq significantly negatively associated hrqol feature hrqol total score 0343 p 0001 95 ci 7080 4077 positive associations bipq features hrqol included personal control 0119 p 0004 95 ci 285714194 treatment control 0084 p 0029 95 ci 064012391 negative associations hrqol identity 0105 p 0034 95 ci 13159 0430 emotional response 0207 p 0001 95 ci 18334 6811 conclusionspatients ra china perceive illness ways affect hrqol results suggest strategies target perceptions may improve quality life patients,0.0
ensemble icluster method analyze longitudinal lncrna expression data psoriasis patients background psoriasis immunemediated inflammatory disorder skin chronic inflammation hyperproliferation epidermis since psoriasis genetic components diseased tissue psoriasis easily accessible natural use highthroughput technologies characterize psoriasis thus seek targeted therapies transcriptional profiles change correspondingly intervention unlike crosssectional gene expression data longitudinal gene expression data can capture dynamic changes thus facilitate causal inferencemethodsusing icluster method building block ensemble method proposed applied longitudinal gene expression dataset psoriasis objective identifying key lncrnas can discriminate responders nonresponders two immune treatments psoriasisresultsusing support vector machine models leaveoneout predictive accuracy 20lncrna signature identified ensemble estimated 80 outperforms several competing methods furthermore pathway enrichment analysis performed target mrnas identified lncrnas enriched go terms kegg pathways proteasome protein deubiquitination included ubiquitinationproteasome system regarded key player psoriasis proteasome inhibitor target ubiquitination pathway holds promises treating psoriasisconclusionsan integrative method icluster multiple data integration can adopted directly analyze longitudinal gene expression data offers promising options longitudinal big data analysis comprehensive evaluation validation resulting 20lncrna signature highly desirable,0.0
multiple sclerosis relapse presenting sensorineural hearing loss neurology 2021 mar 2101212 wnl0000000000011796 doi 101212 wnl0000000000011796 online ahead printno abstractpmid33653899 doi101212 wnl0000000000011796,0.0
leveraging unstructured data identify hereditary angioedema patients electronic medical records background epidemiologic impact hereditary angioedema hae difficult quantify due misclassification retrospective studies resulting nonspecific diagnostic coding aim study identify cohorts patients hae1 2 evaluating structured unstructured data us ambulatory electronic medical record emr databasemethodsa retrospective feasibility study performed using ge centricity emr database 20062017 patients 1 diagnosis code hae1 2 international classification diseases ninth revision clinical modification 2776 international classification diseases tenth revision clinical modification d841 1 physician note regarding hae1 2 6 months data earliest code note index date included two mutually exclusive cohorts created probable hae 2 codes 2 notes separate days suspected hae 1 code note impact manually reviewing physician notes cohort formation assessed demographic clinical characteristics 2 final cohorts describedresultsinitially 1691 patients identified 190 1501 probable suspected hae cohorts respectively physician note review confirmed hae cohort comprised 254 patients suspected hae cohort decreased 1299 patients 138 patients determined hae excluded overall falsepositive rate initial algorithms 82 across final cohorts median age 50 years 60 patients female haespecific prescriptions identified 31 2 confirmed suspected hae cohorts respectivelyconclusionsunstructured emr data can provide valuable information identifying patients hae1 2 research needed develop algorithms representative hae cohorts retrospective studies,0.0
association spectraldomain oct longterm disability worsening multiple sclerosis neurology 2021 mar 2101212 wnl0000000000011788 doi 101212 wnl0000000000011788 online ahead printabstractobjective evaluate whether retinal spectraldomain optical coherence tomography sdoct assessment baseline associated longterm disability worsening people multiple sclerosis pwms performed sdoct expanded disability status scale edss assessments among 132 pwms baseline median 10 years latermethods prospective longitudinal study participants underwent sdoct edss visual acuity va assessments baseline followup statistical analyses performed using generalized linear regression models adjusted age sex race ms subtype baseline disability defined clinically meaningful edss worsening increase 20 baseline edss score 60 increase 10 baseline edss score 60results 132 pwms mean age 43 years n106 patients relapsing remitting ms included analyses median duration followup 104 years multivariable models excluding eyes prior optic neuritis relative patients average baseline ganglion cell+inner plexiform layer gcipl thickness 70m mean gcipl thickness eyes baseline average baseline gcipl thickness 70m associated 4fold increased odds meaningful edss worsening adjusted odds ratio 397 95 ci 1241270 p002 almost 3fold increased odds lowcontrast va worsening adjusted odds ratio 293 95 ci 140613 p004 conclusions lower baseline gcipl thickness sdoct independently associated longterm disability worsening ms accordingly sdoct single timepoint may help guide therapeutic decision making among individual pwmsclassification evidence study provides class evidence lower baseline gcipl thickness sdoct independently associated longterm disability worsening mspmid33653904 doi101212 wnl0000000000011788,0.0
possible role interleukin6 regulator insulin sensitivity patients neuromyelitis optica spectrum disorder background neuromyelitis optica spectrum disorder nmosd associated inflammatory mediators may also trigger downstream signaling pathways leading reduce insulin sensitivitymethodswe aimed determine risk association hyperinsulinemia nmosd patients seropositive aqp4igg serum levels interleukin il 6 il17a compared control groupserum levels metabolic insulin fasting blood sugar fbs lipid profile inflammatory il6 il17 markers assessed 56 nmosd patients 100 controlsresultshyperinsulinemia prevalent nmosd patients independent age sex body mass index bmi 482 vs 26 p 0005 compared control group adjusting age sex bmi significant association lower insulin sensitivity nmosd risk 95 ci beta 073 062 086 p 00001 circulating levels il6 il17 higher nmosd patients il6 effect modifier association lower insulin sensitivity nmosd riskconclusionsour data suggests inflammatory pathogenesis nmosd leads hyperinsulinemia increases risk insulin resistance,0.0
steap4 expression cns resident cells promotes th17 cellinduced autoimmune encephalomyelitis background multiple sclerosis ms debilitating neurological disease caused autoimmune destruction myelin sheath experimental autoimmune encephalomyelitis eae widely used animal model pathogenesis ms others previously demonstrated il17 critical pathogenesis eae concentration il17 significantly higher sera ms patients healthy controls correlates disease activity moreover antiil17 neutralizing antibody demonstrated promising efficacy phase ii trial ms patients substantiating key pathogenic role il17 ms th17 il17 emerging bona fide drivers neuroinflammation remains unclear effector molecule executes inflammatory tissue destruction th17driven eaemethodsby microarray analysis found steap4 downstream molecule il17 signaling eae used steap4 global knockout mice steap4 conditional knockout mice test role pathogenesis eaeresultshere report metalloreductase steap4 key effector molecule participates contributes pathogenesis th17mediated neuroinflammation experimental autoimmune encephalomyelitis steap4 knockout mice displayed delayed onset reduced severity eae induced active immunization reduced disease phenotype due impact steap4 deficiency myelin reactive t cells contrast steap4 knockout mice resistant passively induced eae pointing role steap4 effector stage eae notably steap4 induced spinal cord eae mice received th17 cells th1 cells consistently steap4 deficiency protected th17 th1induced eae finally using nestincre steap4fl fl mice showed ablation steap4 expression resident cells central nervous system attenuated disease severity active immunization passive th17 transferinduced eaeconclusionin study identified steap4 th17specific effector molecule participates contributes pathogenesis neuroinflammation thus potentially provide novel target ms therapy,1.0
value bone marrow liver spleen imaging diagnosis prognostication followup monitoring myeloproliferative neoplasms systematic review background diagnostic treatment response criteria jak2 calr mpl mutationrelated myeloproliferative neoplasms mpns largely based bone marrow bm biopsy results however biopsies several limitations risk sampling error also prognostic impact bm abnormalities largely unclear although currently used clinical practice imaging techniques might offer additional information review investigated value bm liver spleen imaging diagnosis prognostication response monitoring jak2 calr mpl mutationrelated mpns ie essential thrombocythemia et polycythemia vera pv myelofibrosis mf methodsa systematic literature search performed via pubmed embase cochrane library 2020 march 26th 5505 identified records 55 publications met eligibility criteria ie containing original data imaging appearance bm spleen liver adult et pv mf patients published peerreviewed journal written english resultsmany explorative studies described imaging features sometimes comparisons clinical characteristics studies reporting measures diagnostic accuracy included 1 splenic transient elastography predict bm fibrosis grade mf 2 dynamic contrastenhanced mri discern mf patients et patients healthy controls 3 18fluorodeoxyglucose pet detect residual disease stem cell transplantation mf diagnostic accuracies radiography 99mtccolloid scintigraphy derived several articles except study 18fluorodeoxyglucose pet established substantial concerns regarding risk bias applicability across studies using quadas2 tool three publications described correlation imaging results prognosis one quantified effectconclusionsbased current data mri t1weighted stir dixon seems especially promising evaluation bm fat content indirectly cellularity fibrosis mf possibly estimating bm cellularity et pv 18fluorodeoxyglucose 18fluorothymidine pet ct might useful evaluating bm fibrosis good reported accuracy former diagnosis residual disease research techniques warranted determine exact value future researchers improve methodology focus evaluation diagnostic accuracy prognostic implications results,0.0
reduction circulating vitamin d binding protein patients multiple sclerosis background study aimed determine risk association vitamin d binding protein vdbp polymorphism patients multiple sclerosis ms ms biobank difference vdbp serum levels ms patients recently diagnosedmethodthe current casecontrol study performed 296 ms patients 313 controls thereafter two common missense vdbp polymorphisms named rs7041and rs4588 evaluated participants serum levels vitamin d vitamin d binding protein assessed 77 ms patients diagnosed since one year ago 67 healthy people matched terms age sexresultthe frequency distributions vdbp genotypes alleles snp rs7041 rs4588 observed similar ms control groups p 005 vdbp haplotypes gc2 gc2 gc1 gc1 gc1 gc2 found similar ms control groups p 005 subgroup analysis circulating vdbp lower ms patients lnvdbp gr ml 364 091 vs 531 077 p 00001 even adjusting vitamin d levels body mass index taking vitamin d supplement significant association vdbp haplotypes vitamin d levels two groupsconclusionthe present study suggested association lower levels circulating vdbp multiple sclerosis newly diagnosed patients however vdbp causative role development ms still unclear needs studies,0.0
impact bronchoalveolar lavage lymphocytosis effects antiinflammatory therapy idiopathic nonspecific interstitial pneumonia idiopathic pleuroparenchymal fibroelastosis unclassifiable idiopathic interstitial pneumonia background idiopathic nonspecific interstitial pneumonia insip idiopathic pleuroparenchymal fibroelastosis ippfe unclassifiable idiopathic interstitial pneumonia iip iips chronic fibrotic phenotypes unlike idiopathic pulmonary fibrosis often treated antiinflammatory drugs including corticosteroids immunosuppressants however impact bronchoalveolar lavage bal lymphocytosis effects antiinflammatory therapy never evaluated study aimed elucidate whether bal lymphocytosis can used predict efficacy antiinflammatory drugs insip ippfe unclassifiable iipmethodsjapanese patients diagnosed insip ippfe unclassifiable iip multidisciplinary discussion identified using nationwide registry eligible patients stratified four groups without bal lymphocytosis antiinflammatory therapy compare overall survival os changes lung function bal lymphocytosis defined lymphocyte differential count 15 cutoff corroborated survival classification regression tree analysisresultsoverall 186 patients 37 insip 16 ippfe 133 unclassifiable iip analyzed limited patients treated antiinflammatory drugs n 123 patients bal lymphocytosis better prognosis hazard ratio hr 026 95 confidence interval ci 011063 p 0003 higher slope forced vital capacity fvc predicted 2 years longer os logrank test p 0012 without bal lymphocytosis multivariate analysis bal lymphocytosis hr 031 95 ci 013075 p 0009 prognostic factor os along age fvc predicted conversely patients managed without antiinflammatory therapy n 63 presence absence bal lymphocytosis prognostic valueconclusionsbal lymphocytosis associated good outcomes patients treated antiinflammatory drugs prognostic value antiinflammatory drugs used bal lymphocytosis may provide predictive biomarker identifying patients insip ippfe unclassifiable iip likely benefit antiinflammatory drugs,0.0
potential role indolelactate butyrate multiple sclerosis revealed integrated microbiomemetabolome analysis cell rep med 2021 apr 20 2 4 100246 doi 101016 jxcrm2021100246 ecollection 2021 apr 20abstractmultiple sclerosis ms immunemediated disease whose precise etiology unknown several studies found alterations microbiome individuals ms mechanism may affect ms poorly understood analyze microbiome 129 individuals ms find harbor distinct microbial patterns compared controls study functional consequences differences measure levels 1 251 serum metabolites subgroup subjects unravel distinct metabolite signature separates affected individuals controls nearly perfectly auc 097 individuals ms found depleted butyrateproducing bacteria bacteria produce indolelactate intermediate generation potent neuroprotective antioxidant indolepropionate found lower serum identify microbial metabolite candidates may contribute ms explored causal role therapeutic potentialpmid33948576 pmcpmc8080254 doi101016 jxcrm2021100246,1.0
fiveyear trends payments neurologistprescribed drugs medicare part d neurology 2021 mar 10101212 wnl0000000000011712 doi 101212 wnl0000000000011712 online ahead printabstractobjective determine whether increase payments neurologistprescribed drugs performed retrospective analysis prescription claims medicare part d prescriber public use files 20132017methods included claims prescribed providers taxonomy neurology included drugs present five years drugs designated 2013 generic gen brand name bno brand name prescribed even though generic equivalent available bnge observe payment trends percentage change per claim payment compared drug classesresults included 520 drugs 322 gen 61 bno 137 bnge representing 90 716 536 claims generating payments 26 654 750 720 number claims 2013 2017 increased 76 total payment increased 504 adjusted inflation claim payments gen drug increased 06 compared significant increases bno bnge drugs 424 450 ptrend0001 percentage overall gen claims increased 819 880 bno increased 49 62 bnge decreased 133 58 neuroimmunology multiple sclerosis drugs represented 50 total payments despite 43 claimsconclusions payments neurologistprescribed brand name generic drugs medicare part d increased consistently well inflation 20132017 unless overall trend stabilizes reversed high costtoclaim drugs addressed trend will place increasing burden neurologic medicare budgetpmid33692164 doi101212 wnl0000000000011712,0.0
midterm outcomes modified valvesparing aortic root replacement versus bentall procedure middleaged chinese patients acute debakey aortic dissection singlecenter retrospective study background midterm longterm efficacies valve preservation acute debakey aortic dissection ad controversial thus unclear whether middleaged patients acute debakey ad undergo modified valvesparing procedures bentall procedure emergency settingmethodsthis study included 213 middleaged chinese patients 60 years old treated acute debakey ad january 2009 june 2015 treatments involved modified valvesparing aortic root replacement vsarr 117 patients bentall procedure 96 patients preoperative intraoperative postoperative followup data analyzed echocardiography thoracoabdominal computed tomography angiography cta findings reviewed 3 months 1 year annually surgeryresultsno significant differences observed terms preoperative intraoperative inhospital mortality postoperative parameters also significant differences aortic regurgitation ar however followup examinations using cta revealed 6 patients endoleakage distal end triplebranched stent 0 110 patients 00 vs 6 90 patients 67 p 0022 anticoagulationrelated thromboembolism bleeding events significantly lower group group b 0 110 patients 00 vs 11 90 patients 111 p 0001 postoperative aortic valve reoperation rate significantly lower group 1 110 patients 09 vs 8 90 patients 89 p 0020 significant difference survival followup period logrank p 005 conclusionfor middleaged patients acute debakey ad vsarr associated lower rate endoleakage distal end triplebranched stent thromboembolism bleeding events aortic valve reoperation vs bentall procedure,0.0
delayed development aphasia related degeneration arcuate fasciculus dominant hemisphere nine years onset patient intracerebral hemorrhage case report background report patient intracerebral hemorrhage ich showed delayed development aphasia demonstrated via follow diffusion tensor tractography dtt related neural degeneration arcuate fasciculus af case presentationa 51yearold righthanded male presented right hemiparesis occurred onset spontaneous ich left corona radiata basal ganglia brain magnetic resonance images showed hematoma left subcortical area one month onset hemosiderin deposits left subcortical area nine years onset four weeks onset exhibited severe aphasia western aphasia battery wab testing revealed aphasia quotient 396 percentile ile however aphasia improved nearly normal state three months onset aphasia quotient 905 ile approximately eight years onset began show aphasia aphasia increased slowly time resulting wab aphasia quotient 125 ile nine years onset integrity left af hematoma preserved 1month postonset dtt however middle portion left af middle hemosiderin deposits showed discontinuation 9year postonset dtt fractional anisotropy value left af higher 9year postonset dtt 048 1month postonset dtt 035 whereas mean diffusivity value lower 9year postonset dtt 010 1month postonset dtt 032 fiber number left af decreased 175 9year postonset dtt 239 1month postonset dttconclusionswe report patient ich showed delayed development aphasia appeared related degeneration af dominant hemisphere results suggest dtt useful ruling neural degeneration af,0.0
circulating galectin1 galectin3 sera patients systemic sclerosis associations clinical features treatment front pharmacol 2021 apr 20 12650605 doi 103389 fphar2021650605 ecollection 2021abstractsystemic sclerosis ssc rheumatic disease characterized fibrosis microvascular damage immune dysregulation two major subsets limited cutaneous systemic sclerosis lcssc diffuse cutaneous systemic sclerosis dcssc can defined according extent skin involvement increasing evidence indicates role galectins immune vascular programs extracellular matrix remodeling fibrosis suggesting possible involvement ssc determined serum levels galectin gal 1 gal3 83 ssc patients dcssc n 17 lcssc n 64 ssssc n 2 evaluated association clinical manifestations disease patients dcssc showed lower gal3 levels compared lcssc p 0003 whereas considerable difference gal1 levels detected groups remarkably higher concentrations gal1 associated presence telangiectasias p 0015 higher concentrations gal3 associated telangiectasias p 0021 diarrhea p 0039 constipation p 0038 moreover lower gal3 levels associated presence tendinous retractions p 0005 patients receiving calcium blockers p 0048 methotrexate p 0046 immunosuppressive treatment p 0044 presented lower concentrations gal3 compared receiving treatments presence telangiectasia type ssc maintained statistical association gal3 025 p 0022 026 p 0017 respectively multiple linear regression models conclusion serum levels gal3 associated clinical manifestations ssc among presence telangiectasias explained central role lectin vascularization programspmid33959016 pmcpmc8093796 doi103389 fphar2021650605,0.0
implications extreme serum neurofilament light chain levels management patients relapsing multiple sclerosis ther adv neurol disord 2021 apr 20 1417562864211001977 doi 101177 17562864211001977 ecollection 2021abstractbackground serum neurofilament light chain snfl promising biomarker complement decisionmaking process multiple sclerosis ms patients however although snfl levels able detect disease activity predict future disability growing evidence yet translated practicable recommendations implementation clinical routinemethods observation patient extensive inflammatory activity magnetic resonance imaging mri along extremely high snfl level absence clinical symptoms prompted us investigate common characteristics ms patients highest snfl levels retrospective cohort study 975th percentile chosen cutoff value mean snfl level resulting extreme neurofilament light chain nfl cohort corresponded well snfl level presented case patient characterization included clinical mri assessment focus disease activity markers snfl levels determined single molecule arrayresults 975th percentile ms cohort 958 snfl measurements 455 patients corresponded threshold value 461 pg ml mean snfl level extreme snfl cohort n 24 956 pg ml standard deviation 684 interestingly 15 patients suffered relapse time point sample collection whereas nine patients showed signs clinical disease activity snfl levels patients without relapse differ median 813 pg ml interquartile range iqr 480128 versus 802 pg ml iqr 464976 p 0815 proportion patients contrastenhancing lesions high also differ patients without relapse 929 versus 875 p 0538 789 patients receiving highefficacious therapy ongoing disease activity 2year followupconclusion extremely high snfl levels indicative subclinical disease activity might complement treatment decisions ambiguous casespmid33959194 pmcpmc8060778 doi101177 17562864211001977,0.0
utilising multilarge omics data elucidate biological mechanisms within multiple sclerosis genetic susceptibility loci backgroundgenomewide association studies gwas succeeded identifying 200 susceptibility loci multiple sclerosis ms however potential functional variants mechanisms loci affect ms risk remain largely unexplainedobjectiveswe used summary databased mendelian randomisation prioritise risk genes infer potential biological mechanisms ms risk locimethodsthe data used consisted dna methylation n 1980 qtl mqtl gene expression n 31 684 qtl eqtl derived whole blood well ms gwas summary statistics 14 802 cases 26 703 controls findings evaluated using data derived independent brain mqtl n 1160 eqtl n 1194 resultsin whole blood identified two independent genomic loci lincrna rp11326c313 tnfsf14 consistent genomewide significant pleiotropic associations across different omics layers brain tissue similar effect rp11326c313 locus observed tnfsf14 indicating potential tissuespecific effect tnfsf14 locusconclusionwe provide silico evidence putative biological mechanisms identified dna methylation sites target genes functionally relevant ms development different tissues future research targeting genes dna methylation sites will determine roles pathophysiology ms,0.0
getting flow state systematic review flow experience neurological diseases background flow subjective psychological state people report fully involved activity point forgetting time surrounding except activity flow physical cognitive rehabilitation may considerable impact functional outcome especially patients neurological diseases engage exercises using robotics virtual augmented reality serious games tablets computer developing new therapy games measuring flow experience can indicate whether game motivates one train purpose study identify systematically review current literature flow experience assessed patients stroke traumatic brain injury multiple sclerosis parkinsons disease additionally critically appraised compared summarized measurement properties selfreported flow questionnaires used neurorehabilitation setting designa systematic review using prisma cosmin guidelinesmethodsmedline ovid embase ovid cinahl ebsco scopus searched inclusion criteria 1 peerreviewed studies 2 focused investigation flow experience 3 patients neurological diseases ie stroke traumatic brain injury multiple sclerosis parkinsons disease qualitative data synthesis performed present measurement properties used flow questionnaires resultsten studies 911 records met inclusion criteria seven studies measured flow context serious games patients stroke traumatic brain injury multiple sclerosis parkinsons disease three studies assessed flow activities gaming songwriting intervention activities daily living six different flow questionnaires used originally validated healthy people none studies presented psychometric data respective research populationconclusionthe present review indicates flow experience increasingly measured physical cognitive rehabilitation setting patients neurological diseases however psychometric properties used flow questionnaires lacking exergame developers working field physical cognitive rehabilitation patients neurological diseases valid flow questionnaire can help optimize content games optimal engagement can occur gameplay whether flow experiences can ultimately positive effects physical cognitive parameters needs study,0.0
celltypespecific gene modules related regional homogeneity spontaneous brain activity associations common brain disorders front neurosci 2021 apr 20 15639527 doi 103389 fnins2021639527 ecollection 2021abstractmapping gene expression profiles neuroimaging phenotypes anatomical space provides opportunities discover molecular substrates human brain functional properties aimed identify celltypespecific gene modules associated regional homogeneity reho spontaneous brain activity associations brain disorders fourteen gene modules consistently associated reho three datasets five showed celltypespecific expression one neuronendothelial module one neuron module one astrocyte module two microglial modules two independent cell series human cerebral cortex neuronendothelial module mainly enriched transporter complexes neuron module synaptic membrane astrocyte module amino acid metabolism microglial modules leukocyte activation ribose phosphate biosynthesis enrichment analyses celltypespecific modules 10 common brain disorders microglial module significantly enriched genes obtained genomewide association studies multiple sclerosis ms alzheimers disease ad reho spontaneous brain activity associated gene expression profiles neurons astrocytes microglia endothelial cells microgliarelated genes associated ms ad may provide possible molecular substrates reho abnormality brain disorderspmid33958982 pmcpmc8093778 doi103389 fnins2021639527,0.0
seeing finish line can baseline oct values predict longterm disability therapeutic management multiple sclerosis neurology 2021 mar 2101212 wnl0000000000011793 doi 101212 wnl0000000000011793 online ahead printno abstractpmid33653903 doi101212 wnl0000000000011793,0.0
associations healthy lifestyles cerebrospinal fluid biomarkers alzheimers disease pathology cognitively intact older adults cable study abstractobjectivewe aimed investigate associations healthy lifestyles alzheimers disease ad biomarkers cerebrospinal fluid csf methodsa total 1108 cognitively intact individuals chinese alzheimers biomarker lifestyle cable study examined evaluate associations ad biomarkers healthy lifestyle factors including current smoking harmful drinking absence social isolation regular physical activity participants categorized groups favorable intermediate unfavorable lifestyles according lifestyle factors associations overall lifestyle csf biomarkers also analyzedresultsamong cognitively intact older adults social engagement lower csf tau p 0009 ptau p 0001 social isolation regular physical activity associated higher csf a42 p 0013 lower levels csf tau p 0036 ptau p 0007 however significant associations found smoking status alcohol intake csf biomarkers overall lifestyle participants evaluated four lifestyle factors favorable lifestyle profiles related lower levels csf tau p 0001 ptau p 0001 conclusionsthese findings suggest healthy lifestyles beneficial effect ad pathology among cognitively intact elders,0.0
place spinal cord stimulation management patients multiple sclerosis systematic review literature minim invasive surg 2021 apr 19 20219969010 doi 101155 2021 9969010 ecollection 2021abstractobjective spinal cord stimulation scs minimally invasive technique mainly used treat neuropathic pain associated failed back surgery syndrome however therapy utilized treat chronic painful conditions pain associated multiple sclerosis ms nonetheless efficacy scs ms patients fully established fact scs series ms patients represent subset bigger cohort comprises different causes pain motor disorder functional limitations aim study systematically review literature evaluate effectiveness scs ms patientsmethods literature search performed different databases pubmed scopus embase using following terms multiple sclerosis spinal cord stimulation dorsal column stimulation according prisma preferred reporting items systematic reviews metaanalyses guidelinesresults total 452 articles reviewed 7 studies included present analysis 373 ms patients submitted stimulation trial 82 ms patients underwent de novo implantation 285 373 764 cases submitted scs trial enrolled permanent stimulation found longlasting improvement 193 346 558 ms patients motor disorders 90 134 6713 ms patients urinary dysfunction 28 34 8235 ms patients neuropathic pain efficacy scs higher urinary dysfunction p 00144 neuropathic pain p 00030 compared motor disordersconclusions systematic review evidences scs effective ms patients urinary dysfunction pain symptoms seem responsive scs studies needed improve patient selection clarify best timing perform scs patientspmid33986958 pmcpmc8079186 doi101155 2021 9969010,0.0
rare deleterious mutations hnrnp genes result shared neurodevelopmental disorders background increasing number genomic sequencing studies hundreds genes implicated neurodevelopmental disorders ndds rate gene discovery far outpaces understanding genotypephenotype correlations clinical characterization remaining bottleneck understanding ndds diseaseassociated mendelian genes members gene families hypothesize related molecular function share clinical presentationsmethodswe tested hypothesis considering gene families multiple members enrichment de novo variants among ndds determined previous metaanalyses one gene families heterogeneous nuclear ribonucleoproteins hnrnps 33 members five recently identified ndd genes hnrnpk hnrnpu hnrnph1 hnrnph2 hnrnpr two significant enrichment previous metaanalysis probands ndds hnrnpu syncrip utilizing protein homology mutation analyses gene expression analyses phenotypic characterization provide evidence variation 12 hnrnp genes candidates ndds seven potentially novel remaining genes family likely significantly contribute ndd riskresultswe report 119 new ndd cases 64 de novo variants sequencing international collaborations combined published clinical case reports consider 235 cases genedisruptive singlenucleotide variants indels 15 cases small copy number variants three hnrnpencoding genes reach nominal exomewide significance de novo variant enrichment nine candidates pathogenic mutations comparison hnrnp gene expression shows pattern consistent role cerebral cortical development enriched expression among radial glial progenitors clinical assessment probands n 188221 expands phenotypes associated hnrnp rare variants phenotypes associated variation hnrnp genes distinguishes subgroup nddsconclusionsoverall novel approach exploiting gene families ndds identifies new hnrnprelated disorders expands phenotypes known hnrnprelated disorders strongly implicates disruption hnrnps whole ndds supports ndd subtypes likely shared molecular pathogenesis date first study identify novel genetic disorders based presence disorders related genes also perform first phenotypic analyses focusing related genes finally show radial glial expression genes likely critical neurodevelopment important diagnostics well developing strategies best study genes development therapeutics,0.0
effect sirolimus angiomyolipoma determined decrease fatpoor compartments includes striking reduction vascular structures sci rep 2021 apr 19 11 1 8493 doi 101038 s41598021879304abstractrenal angiomyolipomas hemorrhage associated size vascular constitution effects sirolimus different components angiomyolipomas analyzed patients tuberous sclerosis complex sporadic lymphangioleiomyomatosis multiple sporadic angiomyolipomas thirty angiomyolipomas 14 patients treated sirolimus retrospectively evaluated hounsfieldunit threshold used classify angiomyolipomas fatrich fatpoor intermediatefat tumors categorize tumor compartments fat rich fat poor intermediate fat highly vascularized diameter variations measured assess effects aneurysmatic ectatic vascular formations volume reduction following treatment sirolimus higher fatpoor fatrich angiomyolipomas tumor reduction mainly determined decrease fatpoor highlyvascularized compartments volume fatrich compartment increased broad liposubstitution observed tumors median reduction 100 75 100 diameter aneurysmatic ectatic vascular structures observed study showed sirolimus reduces size angiomyolipomas decreasing primarily highlyvascularized fatpoor compartments effect associated remarkable reduction tumoral aneurysms ectatic vessels revealing likely mechanism responsible riskdecreasing effect mtor inhibitors angiomyolipoma bleeding findings support role mtor development angiomyolipoma blood vesselspmid33875750 doi101038 s41598021879304,0.0
hand grip strength fatigability correlation clinical parameters diagnostic suitability cfs background myalgic encephalomyelitis chronic fatigue syndrome cfs complex debilitating disease accompanied muscular fatigue pain functional measure assess muscle fatigability cfs patients however established clinical routine aim study evaluate assessing repeat maximum handgrip strength hgs muscle fatigability diagnostic tool correlation clinical parametersmethodswe assessed hgs 105 patients cfs 18 patients cancer related fatigue crf 66 healthy controls hc using electric dynamometer assessing maximal fmax mean force fmean ten repetitive measurements results correlated clinical parameters creatinine kinase ck lactate dehydrogenase ldh maximum isometric quadriceps strength measurement conducted eight cfs patients eight hcresultsme cfs patients significantly lower fmax fmean hgs compared hc p 00001 fatigue ratio assessing decline strength repeat maximal hgs measurement fmax fmean higher p 00012 recovery ratio identical second testing 60 min later significantly lower cfs compared hc fmean2 fmean1 p 00020 lower hgs parameters correlated severity disease postexertional malaise muscle pain higher ck ldh levels exertionconclusionrepeat hgs assessment sensitive diagnostic test assess muscular fatigue fatigability objective measure assess disease severity cfs,0.0
corrigendum requirement protein geranylgeranylation chemokine receptor signaling th17 cell function animal model multiple sclerosis front immunol 2021 apr 19 12687135 doi 103389 fimmu2021687135 ecollection 2021abstract corrects article doi 103389 fimmu2021641188 pmid33953734 pmcpmc8091873 doi103389 fimmu2021687135,0.0
integrative biochemical proteomics metabolomics cerebrospinal fluid biomarkers predict clinical conversion multiple sclerosis brain commun 2021 apr 19 3 2 fcab084 doi 101093 braincomms fcab084 ecollection 2021abstracteightyfive percent multiple sclerosis cases begin discrete attack termed clinically isolated syndrome 37 clinically isolated syndrome patients experience relapse within 20 years onset thus identification biomarkers able differentiate individuals likely second clinical attack remain clinically isolated syndrome stage essential apply personalized medicine approach sought identify biomarkers biochemical metabolic proteomic screens predict clinically defined conversion clinically isolated syndrome multiple sclerosis generate multiomicsbased algorithm higher prognostic accuracy currently available test integrative multivariate approach applied analysis cerebrospinal fluid samples taken 54 individuals point clinically isolated syndrome 210 years subsequent followup enabling stratification clinical converters nonconverters leukocyte counts significantly elevated onset clinical converters predict occurrence second attack 70 accuracy myoinositol levels significantly increased clinical converters glucose levels decreased predicting transition multiple sclerosis accuracies 72 63 respectively proteomics analysis identified 89 novel gene products related conversion identified biochemical protein biomarkers combined produce algorithm predictive accuracy 83 transition clinically defined multiple sclerosis outperforming individual biomarker isolation including oligoclonal bands identified protein biomarkers consistent exaggerated immune response perturbed energy metabolism multiple sclerosis pathology clinical converter group new biomarkers presented provide novel insight molecular pathways promoting disease multiomics algorithm provides means accurately predict whether individual likely convert clinically defined multiple sclerosispmid33997784 pmcpmc8111065 doi101093 braincomms fcab084,0.0
comprehensive analysis iga nephropathy expression profiles identification potential biomarkers therapeutic agents background iga nephropathy igan kidney disease recognized presence iga antibody depositions kidneys underlying mechanisms complicated disease remained explored still urgent need discovery noninvasive biomarkers diagnosis investigation integrative approach applied mrna mirna expression profiles pbmcs discover gene signature novel potential targets biomarkers iganmethodsdatasets selected gene expression omnibus database quality control checking two datasets analyzed limma identify differentially expressed genes mirnas degs demirs following identification demirtarget genes data integration intersecting mrnas subjected different bioinformatic analyses intersecting mrnas demirs related transcription factors trrust database longnon coding rnas lnctard database used construction multilayer regulatory network via cytoscaperesultgse25590 mirna gse73953 mrna datasets analyzed integration 628 intersecting mrnas identified mrnas mainly associated innate immune system apoptosis well ngf signaling pathways multilayer regulatory network constructed several hubdegs tp53 stat3 jun etc demirs mir124 let7b etc tfs nfkb etc lncrnas hotair etc introduced potential factors pathogenesis iganconclusionintegration two different expression datasets construction multilayer regulatory network provided deeper insight pathogenesis igan also introduced several key molecules potential therapeutic target noninvasive biomarkers,0.0
coexistence multiple sclerosis germinoma adult male case report surg neurol int 2021 apr 19 12177 doi 1025259 sni_867_2020 ecollection 2021abstractbackground concurrent diagnosis multiple sclerosis ms central nervous system cns germinoma rare diagnostic criteria ms rely primarily clinical presentation cns germinoma can present ms mimic factors contribute rarity dual diagnosiscase description 28yearold man presented initially bilateral optic neuritis manifesting persistently worsening vision 2 years demyelinating plaques identified within corpus callosum magnetic resonance imaging initial workup addition clinical presentation led diagnosis ms three months following diagnosis ms patient presented obstructive hydrocephalus due newly diagnosed intraventricular mass patient underwent endoscopic third ventriculostomy biopsy confirmed diagnosis cns germinomaconclusion best knowledge dual presentation ms cns germinoma never reported literature clinical presentation bilateral optic neuritis persisting roughly 2 years initial ms diagnosis demyelinating plaques intrathecal oligoclonal bands development intraventricular mass indicates ms cns germinoma presented simultaneously patient treatment plan patient included carboplatin + etoposide followed adjuvant radiation subsequent ivig therapypmid34084605 pmcpmc8168793 doi1025259 sni_867_2020,1.0
covid19 pandemicrelated changes wellness behavior among older americans background covid19 taken toll citizens 50 states united states united states us leads world 30 291 863 confirmed reported cases 549 664 deaths march 29 2021 compared globally confirmed cases 127 442 926 2 787 915 deaths march 29 2021 us federal government primarily left response virus individual states implemented varying measures designed protect health citizens states economic wellbeing unintended consequences virus measures stop spread may include decreased physical activity exercise shifting access consumption food lower qualityoflife therefore primary goal quantify impact covid19 health wellbeing measuring changes physical activity mental healthquality life food security nutrition adults ages 40 older believed shifts health behaviors prevalent minorities less educated lower socioeconomic status older adults underlying health conditions secondary goal determine impact covid19 subpopulationsmethodswe conducted online survey 9969 adults 40 years older 9 august 15 september 2020 urban areas across four us census regions survey included questions demographic variables preexisting health conditions physical activity access food qualityoflife nutritional food status asked participants respond information prepandemic pandemic conditions used pairedsample ttests detect changes variables start pandemic cohens d determine effect sizesresultsour main findings showed decrease physical activity since onset covid19 minorities nonminorities food security also slightly increased minorities pandemic found changes food security qualityoflife indicators nutritional status responded surveyconclusionsit concerning physical activity declined activity helps maintain physical mental health also important time socialize many older adults many ways data indicate older adult population us cities may resilient expected pandemic however pandemic negative impacts detect either due survey instrument timing survey health wellbeing older adults continue monitored order mitigate potential negative impacts,0.0
evolution antibody titres epsteinbarr virus human herpesvirus 6a b expression multiple sclerosisassociated retrovirus serum pregnant multiple sclerosis patients sci rep 2021 apr 19 11 1 8441 doi 101038 s41598021879411abstractepsteinbarr virus ebv human herpesvirus 6a b hhv6a b multiple sclerosis ms associated retrovirus msrv described possible ms triggers analysed antibody titres ebv hhv6 msrv envelope env mrna expression serum pregnant multiple sclerosis patients pms study possible link clinical activity ms pregnancy postpartum possible role relapse predictors purpose serum samples collected 71 pregnant women 50 pregnant ms 21 pregnant healthy controlsphc pregnancy postpartum relating antibody titres igm antibody titres hhv6a b significantly higher pms phc pregnancy trimester postpartum period moreover igm antibody titres hhv6a b higher pms suffered relapse postpartum regarding msrv env mrna expression prevalence first trimester pregnancy significantly higher pms suffered relapses pregnancy summing high igm antibody titres hhv6a b msrv env mrna expression first trimester pregnancy act relapse predictors gestation postpartum periodspmid33875702 doi101038 s41598021879411,0.0
circulating cellfree dna potential diagnostic tools amyotrophic lateral sclerosis neurosci lett 2021 mar 8135813 doi 101016 jneulet2021135813 online ahead printabstractdna methylation garnered much attention recent years diagnostic potential multiple conditions including cancer neurodegenerative diseases conversely advances regarding potential diagnostic relevance dna methylation status sparse field amyotrophic lateral sclerosis als even though patients diagnosed condition significantly benefit improved molecular assays aimed furthering current diagnostic therapeutic options available review will provide overview current diagnostic approaches available als diagnosis discuss potential clinical usefulness dna methylation will also present examples dna methylation diagnostic tool various types cancer neurodegenerative conditions expand circulating cfdna methylation may leveraged early detection als general article will reinforce importance cfdna methylation diagnostic tools will highlight clinical relevance persons diagnosed alspmid33705931 doi101016 jneulet2021135813,0.0
prediction survival amyotrophic lateral sclerosis nationwide danish cohort study abstractintroductionamyotrophic lateral sclerosis als progressive motor neuron disease great heterogeneity biological prognostic markers needed patients plan future supportive treatment palliative treatment endoflife decisions addition prognostic markers greatly needed randomization clinical trialsobjectivethis study aimed test als functional rating scalerevised alsfrsr progression rate fs prognostic marker survival danish als cohortmethodsthe alsfrsr score test date association duration symptoms onset symptoms test date defined fs calculated 90 danish patients diagnosed either probable definite sporadic als median survival time estimated onset symptoms primary endpoint either death tracheostomy fs subjected survival analysis using cox proportional hazards modelling logrank test kaplanmeier survival analysisresults conclusionsboth fs age found strong predictors survival danish als cohort variables easily obtained time diagnosis used clinicians als patients plan future supportive palliative treatment furthermore fs simple prognostic marker predicts survival early phase disease well later stages disease,0.0
german translation cultural adaptation validation unidimensional selfefficacy scale multiple sclerosis background selfefficacy concerns individuals beliefs capability exercise control specific situations complete tasks successfully people multiple sclerosis pwms selfefficacy associated physical activity levels quality life validated german language selfefficacy scale pwms missing aims study translate unidimensional selfefficacy scale multiple sclerosis usems german establish face content validity cultural adaptation german version pwms austria aim validate german usems usemsg pwmsmethodspermission translate validate usems received scale developers following guidelines translation validation questionnaires applying banduras concept selfefficacy usems forwardbackward translated content face validity established cultural adaptation austria performed using cognitive patient interviews reliability assessed using cronbachs alpha person separation index lins concordance correlation coefficient rasch analysis employed assess construct validity comparison made scales resilience general selfefficacy anxiety depression multiple sclerosis fatigue healthrelated quality life data also pooled historic english dataset compare english german language versionsresultsthe translation cultural adaptation successfully performed adaptation process usemsg pretesting conducted 30 pwms validation final usemsg involved 309 pwms minimal severe disability usemsg found valid rasch model fitting scale data using bifactor solution two superitems shown unidimensional free differential item functioning well targeted study population excellent convergent knowngroups validity internal consistency person separation reliability testretest reliability shown usemsg pooling english german datasets confirmed invariance item difficulties languagesconclusionthe usemsg robust valid reliable scale assess selfefficacy pwms can generate interval level data equivalent metric uk versiontrial registrationisrctn registry isrctn14843579 prospectively registered 02 01 2019,0.0
immunophenotypic characterization tcr t cells mait cells hivinfected individuals developing hodgkins lymphoma background despite successful combined antiretroviral therapy cart risk nonaids defining cancers nadcs remains higher hivinfected individuals general population reason increase highly disputed hypothesized tcell receptor tcr cells mucosalassociated invariant t mait cells might associated increased risk nadcs t cells mait cells serve link adaptive innate immune system also exert direct antiviral antitumor activitymethodswe performed longitudinal phenotypic characterization tcr cells mait cells hivinfected individuals developing hodgkins lymphoma hl common type nadcs cryopreserved pbmcs hivinfected individuals developing hl matched hivinfected controls without w o hl healthy controls used immunophenotyping polychromatic flow cytometry including markers activation exhaustion chemokine receptorsresultswe identified significant differences cd4+ t cell count hivinfected individuals developing hl hivinfected matched controls within 1 year cancer diagnosis observed substantial differences cellular phenotype mainly healthy controls hiv infection irrespective hl number markers tended different v1 mait cells hiv+hl+ patients vs hiv+ w o hl patients notably observed significant differences expression ccr5 ccr6 cd16 two groups hiv+ patientsconclusiontcr v1 mait cells hivinfected individuals developing hl show subtle phenotypical differences compared ones hivinfected controls may go along functional impairment thereby may less efficient detecting eliminating malignant cells results support potential longitudinal cd4+ t cell count analysis identification patients higher risk develop hl,0.0
assessment tuberous sclerosisassociated neuropsychiatric disorders using minikid tool pediatric casecontrol study background tuberous sclerosisassociated neuropsychiatric disorders tand previously studied china aimed assess psychiatric level individuals tand using mini international neuropsychiatric interview children minikid chinaresultsa total 8316 individuals 79 95 least one tand 7053 67 95 intellectual disability minikid tool diagnosed 16 neuropsychiatric diseases common attentiondeficit hyperactivity disorder adhd 5158 49 95 social anxiety disorder 3053 29 95 number children psychiatric diseases tuberous sclerosis complex tsc group significantly greater number typically developing group p 00001 notably 6947 66 95 two psychiatric disorders pervasive developmental disorder pdd often comorbid psychiatric disordersconclusionsthis study used structured systematic minikid scale determine diagnosis psychiatric comorbidities relatively large sample suggesting higher rate comparing status individuals tsc typically developing children results suggests neuropsychiatric comorbidities significantly higher individuals tsc research revealed frequent presence two three neuropsychiatric diseases individuals tsc,0.0
expanding medical student interaction neurology redesigned student interest group neurology sign chapter background student interest group neurology sign chapters across medical schools united states provide opportunities medical students participate clinical research service activities neurology despite applicants field neurology traditionally lowmethodsfollowing changes introduced open board style sign chapter executive committee greater active engagement first second year students new activities included journal clubs hands workshops celebration cause events example als walk addition free neurology clinic introduced activities planned consultation office medical education organized times data student enrollment activities successfully carried students interested neurology residency number neurologyrelated research projects student involvement collected prior changes compared values changes introducedresultspost intervention student engagement neurology activities projects increased significantly however similar increase applications neurology residency yet observedconclusionsan open chapter early engagement involvement first second year medical students creating variety chapter activities greater hands involvement planned conjunction office medical education reinvigorated sign chapter,0.0
klebsiella pneumoniae pneumonia patients rheumatic autoimmune diseases clinical characteristics antimicrobial resistance factors associated extendedspectrum lactamase production background past decades klebsiella pneumoniae k pneumoniae infections increasing affected immunocompromised patients nosocomially communally extendedspectrum lactamase esbl production becoming major concern patients rheumatic autoimmune diseases mostly receiving immunosuppressive therapy vulnerable various infections including k pneumoniae however investigated k pneumoniae infections specific population study aimed identify factors associated esbl production mortality k pneumoniae pneumonia among patients rheumatic autoimmune diseases emergency departmentmethodswe retrospectively investigated patients rheumatic diseases diagnosed k pneumoniae pneumonia diagnosis k pneumoniae pneumonia based clinical manifestations radiological findings microbiological testing results prognostic factors risk factors esbl production determined univariate multivariate logistic regression analysis empirical therapy antimicrobial susceptibility data also collectedresultsof 477 k pneumoniae pneumonia patients 60 enrolled study inhospital mortality 283 septic shock icu admission need mechanical ventilation change antibiotics due clinical deterioration related mortality included unfavorable clinical outcomes multivariate analysis suggested esbl production 6793 p 0012 initial pct 05 ng ml 5024 p 0033 respiratory failure admission 4401 p 0046 predicted increased mortality esbl production significantly associated dose corticosteroids 1033 p 0008 cmv viremia 4836 p 0032 patients rheumatic autoimmune diseases abnormal leukocyte count 0192 p 0036 identified protective factor esblproducing k pneumoniae pneumonia commonly used empirical antibiotic ceftazidime isolates showed less resistance carbapenems amikacin susceptibility testingconclusionsk pneumoniae pneumonia lifethreatening patients rheumatic autoimmune diseases findings suggested esbl production initial pct 05 ng ml respiratory failure admission independent factors associated poor prognosis dose corticosteroids cmv viremia predicting esbl production k pneumoniae pneumonia may help make individualized antibiotic decisions clinical practice,0.0
mtor inhibitor improves autisticlike behaviors related tsc2 haploinsufficiency following developmental status epilepticus background tuberous sclerosis complex tsc multisystem genetic disorder often associated autism spectrum disorder asd caused mutations tsc1 tsc2 lead constitutive overactivation mammalian target rapamycin mtor several tsc1+ tsc2+ animal models cognitive social behavior deficits reversed mtor inhibitors however phase ii studies shown amelioration asd cognitive deficits individuals tsc mtor inhibitor therapy asked developmental epilepsy common majority individuals tsc absent animal models explain discrepancymethodsat postnatal day p12 developmental status epilepticus dse induced male tsc2+ eker wildtype rats establishing four experimental groups including controls adult animals n 36 behavior assessed paradigms social interaction test elevated plusmaze lightdark test ymaze novel object recognition testing carried medication t1 2week treatment mtor inhibitor everolimus t2 8week washingout t3 electroencephalographic eeg activity recorded separate set animals n 18 resultsboth tsc2+ mutation dse caused social behavior deficits epileptiform eeg abnormalities t1 everolimus led persistent improvement social deficit induced tsc2+ deficits related dse respond everolimus t2 t3 conclusionsthese findings may contribute explanation asd symptoms individuals tsc comorbid earlyonset epilepsy common reliably ameliorated mtor inhibitors clinical studies,0.0
novel mscbased immune induction strategy aboincompatible liver transplantation phase ii randomized openlabel controlled trial background aboincompatible liver transplantation aboi lt become rescue therapeutic option patients severe hepatic failure although use rituximab greatly reduces morbidity antibodymediated rejection amr severe adverse effects infection biliary complications still seriously threaten survival transplant recipients aim study evaluate safety feasibility using mesenchymal stem cells mscs replace rituximab aboi ltmethodstwentytwo patients severe hepatic failure undergoing aboi lt enrolled randomly divided two groups msc group rituximab group safety application mscs incidence allograft rejection including antibodymediated rejection amr acute cellular rejection acr evaluated groups 2year followup period primary endpoints recipients graft survival postoperative complications compared secondary endpointsresultsno severe mscrelated adverse events observed trial msc treatment yielded comparable better results rituximab decreasing incidence acute rejection 91 vs 273 inspiringly compared rituximab group rates biliary complications 0 vs 455 infection 91 vs 818 significantly decreased msc group addition significant differences 2year graft recipient survival two groups 818 vs 727 conclusionsour data show msc transfusion comparable rituximab treatment amr prophylaxis following aboi lt additionally results indicate mscs beneficial prevention infection biliary complications may introduced novel immunosuppressive approach aboi lttrial registrationtrial registration chictrorgcn chictr2000037732 registered 31 august 2020 retrospectively registered http wwwchictrorgcn showprojaspxproj57074,0.0
association small intestinal bacterial overgrowth parkinsons disease systematic review metaanalysis abstractobjectiveparkinsons disease pd second prevalent neurodegenerative disease alzheimers disease ad worldwide prevalence small intestinal bacterial overgrowth sibo pd patients high conducted comprehensive systematic review metaanalysis determine association sibo pdmethodsa comprehensive literature search pubmed cochrane library embase databases performed identify studies correlating sibo pd studies screened relevant data extracted analysed calculated pooled prevalence sibo individuals pd compared prevalence sibo two groups calculate odds ratio 95 confidence interval ci eggers test performed assess publication biasresultseleven studies 973 participants met inclusion criteria pooled prevalence sibo patients pd 46 95 ci 3656 randomeffects model applied given heterogeneity i2 83 detected among studies eggers test indicated publication bias p 00657 subgroup analyses showed prevalence sibo greater studies including patients diagnosed using lactulose hydrogen breath test lbt 51 95 ci 3765 including patients diagnosed using glucose hydrogen breath test gbt 35 95 ci 2050 prevalence sibo pd highest 55 95 ci 3872 patients diagnosed lbt gbt prevalence sibo 52 95 ci 4064 among patients western countries 33 95 ci 2243 among patients eastern countries pooled sibo pd patients compared healthy controls 522 95 ci 333819 p 000001 identify obvious predictor sibo pd patientsconclusionin conclusion metaanalysis found strong association sibo pd approximately half pd patients testing positive sibo relationships significantly differed based diagnostic test geographic area,0.0
mir126 il7 cxcr1 2 receptors inflammation circulating endothelial progenitor cells study targets treatment pathways model subclinical cardiovascular disease type 1 diabetes mellitus background type 1 diabetes t1dm associated premature cardiovascular disease cvd proinflammatory state whilst proangiogenic mir1263p 5p may play role cvd animal studies established mir126 proangiogenic hypothesised mir1263p 5p reduced t1dm whilst proinflammatory cytokines increasedmethods29 well controlled t1dm patients without cvd 20 healthy controls hcs studied mir1263p 5p assayed plasma peripheral blood mononuclear cells pbmcs whilst chemokine cxc receptor 1 2 cxcr1 2 mrna pbmcs realtime quantitative pcr cytokines assayed mesoscale discovery ingenuity pathway analysis ipa used predict target genes cellular functions pathological states regulated mir1263p 5p ipa generated direct indirect causations different targets analysed whether effects inhibitory stimulatory based published evidenceresultst1dm patients relatively good diabetic control hba1c 74 07 573 76 mmol mol homeostatic cytokine il7 proinflammatory cytokines il8 tnf vascular endothelial growth factorc vegfc increased t1dm versus hcs p 0008 p 0003 p 0041 p 0013 respectively mir1265p significantly upregulated pbmcs t1dm versus hcs p 001 plasma mir1263p unchanged cxcr1 2 elevated t1dm versus hcs p 0009 p 0001 respectively mir1265p positively correlated cxcr1 2 hba1c whilst negatively correlated circulating endothelial progenitor cells cd34+cd133+cd45dim fibronectin adhesion assay combined group t1dm patients hcs p 0028 p 0049 p 0035 p 0047 p 0004 respectively ipa predicted mir1265p antiinflammatory inhibition chemokine cc motif ligand 27 chymotrypsinlike elastase 2a il7 whilst mir1263p direct antiinflammatory effect simultaneously ipa predicted il7 upstream cytokine targetconclusionst1dm without apparent cvd diabetic complications inflammatory state characterised raised proinflammatory cytokines also increased receptor cxcr1 2 mir1265p mir1265p upregulation may represent compensatory response promir1265p therapies antiil7 therapies may new option reduce inflammation cvd risk t1dm research required large prospective study patients t1dm,0.0
lifestyle exercise activity package people living progressive multiple sclerosis leapms adaptions covid19 pandemic remote delivery improved efficiency leapms lifestyle exercise activity package people living progressive multiple sclerosis study developed individualised supported selfmanagement approach physical activity p,0.0
high rates jcv seroconversion large international cohort natalizumabtreated patients ther adv neurol disord 2021 apr 16 141756286421998915 doi 101177 1756286421998915 ecollection 2021abstractaims retrospectively assess factors associated john cunningham virus jcv seroconversion natalizumabtreated patientsbackground natalizumab highly effective treatment relapsingremitting multiple sclerosis rrms use complicated opportunistic jcv infection virus can result progressive multifocal leukoencephalopathy pml serial assessment jcv serostatus mandated natalizumab treatmentmethods patients treated natalizumab rrms six tertiary hospitals melbourne australia n 865 11 ms treatment centres brazil n 136 assessed change jcv serostatus duration exposure natalizumab prior immunosuppression sensitivity analyses examined whether sex age tertiary centre prior immunosuppression number jcv tests affected time seroconversionresults cohort 1001 natalizumabtreated patients durable positive seroconversion observed 83 345 initially jcv negative patients 241 73 per year conversely 16 165 initially jcv positive patients experienced durable negative seroconversion 97 38 per year forty patients 39 fluctuating serostatus timetoevent analysis identify relationship jcv seroconversion duration natalizumab exposure prior exposure immunosuppression associated increased hazard positive jcv seroconversion male sex associated increased jcv seroconversion risk adjusted hazard ratio 209 95 confidence interval 117371 p 0012 conclusion large international cohort natalizumabtreated patients observed annual durable positive seroconversion rate 73 rate exceeds noted registration postmarketing studies natalizumab rate also greatly exceeds predicted epidemiological studies jcv seroconversion healthy populations taken together findings support emerging evidence natalizumab causes offtarget immune changes may trophic jcv seroconversion addition male sex may associated increased positive jcv seroconversionpmid33948117 pmcpmc8053827 doi101177 1756286421998915,0.0
longitudinal analysis t1w#x2f t2w ratio patients multiple sclerosis first clinical presentation backgroundcrosssectional studies suggest normal appearing white matter nawm integrity loss may lead cortical atrophy latestage relapsingremitting multiple sclerosis ms objectiveto investigate relationship nawm integrity cortical thickness first clinical presentation longitudinallymethodsnawm integrity cortical thickness assessed 3t magnetic resonance imaging mri 102 patients clinically isolated syndrome early ms 332 201601 years old 68 female first clinical presentation 2816years fifty healthy controls hcs matched age sex included nawm integrity evaluated using standardized t1w t2w ratio st1w t2w association st1w t2w cortical thickness assessed using linear mixed models effect disease activity investigated using evidence disease activity neda3 criteriaresultsat baseline st1w t2w p0152 cortical thickness p0489 differ hcs longitudinally decreasing st1w t2w associated cortical thickness increasing lesion burden marginal r20061 association modulated failing neda3 marginal r20097 conclusionst1w t2w may useful mri biomarker early ms detecting relevant nawm damage time using conventional mri scans although less sensitivity compared quantitative measures,0.0
inflammation multiple sclerosis ther adv neurol disord 2021 apr 16 1417562864211007687 doi 101177 17562864211007687 ecollection 2021abstractmultiple sclerosis ms chronic inflammatory disease central nervous system cns characterised pathologically demyelination gliosis neuroaxonal damage inflammation despite intense research underlying pathomechanisms driving inflammatory demyelination ms still remain incompletely understood thought caused autoimmune response towards cns selfantigens genetically susceptible individuals assuming autoreactive t cells diseaseinitiating immune cells yet b cells recognized crucial immune cells disease pathology including antibodydependent independent effects moreover myeloid cells important contributors ms pathology becoming increasingly evident different cell types act concert ms immunopathology supported finding beneficial effects actual existing diseasemodifying therapies attributed one single immune celltype rather involve immunological cooperation current strategy ms therapies thus aims shift immune cell repertoire proinflammatory towards antiinflammatory phenotype involving regulatory t b cells antiinflammatory macrophages although existing therapy actually exists directly induces enhanced regulatory immune cell pool numerous studies identified potential net effects cell types review gives conceptual overview t cells b cells myeloid cells immunopathology relapsingremitting ms discusses potential contributions actual diseasemodifying therapies immune cell phenotypespmid33948118 pmcpmc8053832 doi101177 17562864211007687,1.0
acute retrobulbar optic neuritis antimyelin oligodendrocyte glycoprotein antibodyassociated disease complicated microscopic polyangiitis case report medicine baltimore 2021 apr 16 100 15 e24889 doi 101097 md0000000000024889abstractrationale antimyelin oligodendrocyte protein antibodyassociated disease mogad new disease entity various clinical phenotypes mogad often present recurrent optic neuritis can also develop compartment neuromyelitis optica spectrum disorder nmosd moreover multiple autoantibodies antimyeloperoxidase antineutrophil cytoplasmic antibody mpoanca reported serum patients nmosdpatient concerns report 86yearold woman 2year history microscopic polyangiitis mpa patient rapid loss vision left eye abnormal findings observed left fundus tested negative mpoanca upon admission however antimog antibodies observed patients serum cerebrospinal fluiddiagnosis diagnosis mogad complicated mpa madeinterventions patient received twice steroid pulse therapy oral azathioprine maintenance therapyoutcomes vision rapidly recovered subsequent relapse observed 8month observation periodconclusion best knowledge first case mogad complicated mpa steroid pulse therapy azathioprine therapy effective caused mogadpmid33847609 doi101097 md0000000000024889,1.0
pain management inflammatory bowel disease feasibility online therapistsupported cbtbased selfmanagement intervention background chronic pain poorly managed symptom inflammatory bowel disease ibd cognitive behavioural therapy cbt evidence base functional gastrointestinal conditions chronic pain study aimed test feasibility acceptability 9week online facilitatorsupported cbt intervention tailored people chronic ibdrelated paindesigna singlearm prepost design nested qualitative interviews used twenty individuals ibd chronic pain recruited online ibd charity consented research previous survey responded online charity advert individuals indicated paininterference score 4 10 brief pain inventory met inclusion criteria invited take part outcomes included recruitment retention rates pain interference severity quality life qol psychosocial measuresresultsof 145 individuals contacted 55 379 responded two individuals recruited study advertisement twenty 57 351 met screening eligibility criteria eightyfive percent sample engaged intervention sessions 55 completed least 5 9 sessions eighty percent recruited participants completed postintervention questionnaire week 9 mean score overall acceptability 434 070 qualitative feedback demonstrated value thought monitoring facilitator support scores improved qol pain selfefficacy reduced depression anxiety pain catastrophising avoidance resting behaviourconclusionsonline cbt chronic ibdrelated pain appears feasible acceptable study suggests positive effects improving qol reducing psychological distress however online facetoface recruitment methods recommended establishing efficacy larger randomised controlled trials required,0.0
osteopathia striata cranial sclerosis 2021 apr 15 adam mp ardinger hh pagon ra wallace se bean ljh mirzaa g amemiya editors genereviews internet seattle wa university washington seattle 19932021abstractclinical characteristics females osteopathia striata cranial sclerosis oscs present macrocephaly characteristic facial features frontal bossing hypertelorism epicanthal folds depressed nasal bridge prominent jaw approximately half associated features including orofacial clefting hearing loss minority degree developmental delay usually mild radiographic findings cranial sclerosis sclerosis long bones metaphyseal striations combination macrocephaly can considered pathognomonicmales can present mild severe phenotypemildly affected males clinical features similar affected females including macrocephaly characteristic facial features orofacial clefting hearing loss mildtomoderate learning delays mildly affected males likely females congenital musculoskeletal anomalies radiographic findings include cranial sclerosis sclerosis long bones metaphyseal striations common males mosaic amer1 pathogenic variantthe severe phenotype manifests males multiplemalformation syndrome lethal midtolate gestation neonatal period congenital malformations include skeletal defects eg polysyndactyly absent hypoplastic fibulae congenital heart disease brain genitourinary gastrointestinal anomalies macrocephaly always present longitudinal metaphyseal striations observed severely affected males except mosaic amer1 pathogenic variantdiagnosis testing diagnosis oscs established female proband characteristic features heterozygous pathogenic variant amer1 identified molecular genetic testing diagnosis oscs established male proband characteristic features hemizygous pathogenic variant amer1 identified molecular genetic testingmanagement treatment scoliosis management per orthopedic surgeon physiotherapy may helpful joint contractures management oral facial clefts per otolaryngologist hearing loss managed audiology speech language therapy otolaryngology vision loss management per ophthalmologist neurosurgery nerve compression indicated early intervention services special education indicated standard treatments cardiac genitourinary gastrointestinal anomalies wilms tumor malignancysurveillance annual clinical assessment skeletal manifestations scoliosis joint contractures stress fractures persistent bone pain annual audiology ophthalmology evaluations evidence cranial nerve compression due sclerotic bone disorder consider abdominal ultrasound every three months age seven years screen wilms tumorgenetic counseling oscs inherited xlinked manner risk sibs male proband depends genetic status mother risk sibs female proband depends genetic status mother father mother proband amer1 pathogenic variant chance transmitting pregnancy 50 father proband amer1 pathogenic variant presumed will transmit amer1 pathogenic variant daughters none sons date paternal transmission reported mosaic fathers females inherit amer1 pathogenic variant will heterozygotes will variable manifestations oscs males inherit pathogenic variant will hemizygotes will variable manifestations ranging midlate gestation neonatal lethality mild phenotype amer1 pathogenic variant identified affected family member prenatal preimplantation genetic testing possiblepmid33856753 bookshelfnbk569515,0.0
usability mobile app realtime assessment fatigue related symptoms patients multiple sclerosis observational study jmir mhealth uhealth 2021 apr 16 9 4 e19564 doi 102196 19564abstractbackground although fatigue one debilitating symptoms patients multiple sclerosis ms pathogenesis well understood neurogenic inflammatory endocrine metabolic mechanisms proposed taking account temporal dynamics comorbid mood symptoms fatigue may help differentiate fatigue phenotypes phenotypes may reflect different pathogeneses may respond different mechanismspecific treatments although several tools developed assess various symptoms including fatigue monitor clinical status improve perceived level fatigue patients ms options detailed realtime assessment msrelated fatigue relevant comorbidities still limitedobjective study aims present novel mobile app specifically designed differentiate fatigue phenotypes using circadian symptom monitoring stateoftheart characterization msrelated fatigue related symptoms also aim report first findings regarding patient compliance relationship compliance patient characteristics including ms disease severitymethods developing app used prospective study designed investigate brain magnetic resonance imaging correlates msrelated fatigue total 64 patients ms recruited study asked use app 2week period app features following modules visual analogue scales vass assess circadian changes fatigue depression anxiety pain daily sleep diaries slds assess sleep habits quality 10 onetime questionnaires assess fatigue depression anxiety sleepiness physical activity motivation well several onetime questionnaires created assess relevant aspects fatigue captured existing fatigue questionnaires app prompts subjects assess symptoms multiple times day enables realtime symptom monitoring webaccessible portalresults 64 patients 56 88 used app 51 91 completed onetime questionnaires 47 84 completed onetime questionnaires vass slds patients reported issues usage app technical issues webbased data collection system relapsingremitting ms secondaryprogressive ms ratio significantly higher patients completed onetime questionnaires vass slds completed onetime questionnaires vass slds p01 significant differences demographics fatigue disease severity observed degrees complianceconclusions app can used reasonable compliance across patients relapsingremitting secondaryprogressive ms irrespective demographics fatigue disease severitypmid33861208 doi102196 19564,0.0
calciumdependent cytosolic phospholipase a2 activation implicated neuroinflammation oxidative stress associated apoe4 background apolipoprotein e4 apoe4 associated greater response neuroinflammation risk developing lateonset alzheimers disease ad mechanisms association clear activation calciumdependent cytosolic phospholipase a2 cpla2 involved inflammatory signaling elevated within plaques ad brains relation apoe4 genotype cpla2 activity knownmethodsmouse primary astrocytes mouse human brain samples differing apoe genotypes collected measuring cpla2 expression phosphorylation activity relation measures inflammation oxidative stressresultsgreater cpla2 phosphorylation cpla2 activity leukotriene b4 ltb4 levels identified apoe4 compared apoe3 primary astrocytes brains apoetargeted replacement apoetr mice human brain homogenates inferior frontal cortex patients ad carrying apoe3 e4 compared apoe3 e3 greater cpla2 phosphorylation also observed human postmortem frontal cortical synaptosomes primary astrocytes treatment recombinant apoe4 ex vivo apoe4 astrocytes greater levels ltb4 reactive oxygen species ros inducible nitric oxide synthase inos reduced cpla2 inhibitionconclusionsour findings implicate greater activation cpla2 signaling system apoe4 represent potential drug target mitigating increased neuroinflammation apoe4 ad,0.0
early neuropsychological markers cognitive involvement multiple sclerosis j neurol sci 2021 feb 17 423117349 doi 101016 jjns2021117349 online ahead printabstractbackground cognitive impairment due multiple sclerosis ms common often limits occupational functioning contributes disability reduces quality life early detection cognitive involvement ms critical treatment planning intervention frequent regular cognitive monitoring may provide insight subtle changes disease progressionobjective compare sensitivity specificity clinical computerbased experimental measures early cognitive involvement msmethods cognitive functioning compared ms participants early disease course matched healthy controls using conventional computerbased functional assessments brief international cognitive assessment ms bicams computerbased cogstate brief battery cbb attention network testinteraction anti including intraindividual variability test everyday cognitive ability teca functional measure instrumental activities daily livingresults ms participants n 25 mean disease duration 582 365 years demographically matched healthy controls n 29 completed cognitive assessments cogstate measure choice reaction time auc 073 p 004 intraindividual variability anti auc 079 p 001 teca auc 078 p 001 scores sensitive specific markers cognitive involvement msconclusions brief repeatable computerbased measures reaction time variability detect early ms associated cognitive involvementpmid33639421 doi101016 jjns2021117349,0.0
necrotizing fasciitis breast underlying autoimmune disease eur j case rep intern med 2021 apr 15 8 4 002434 doi 1012890 2021_002434 ecollection 2021abstractnecrotizing fasciitis serious soft tissue infection causes necrosis subcutaneous tissues muscle fascia associated high mortality rate around 25 necrotizing fasciitis breast rare entity rapidly progressive lifethreatening condition can lead sepsis multiple organ failure describe case necrotizing fasciitis right breast 48yearold patient diagnosed systemic sclerosisrheumatoid arthritis overlap syndromelearning points necrotizing fasciitis breast challenging diagnosis due rarity similarity simple breast infectionit lifethreatening condition can lead systemic shock multiple organ dysfunction syndrome deathit may occur patients rheumatic diseases treated corticosteroids immunosuppressant drugspmid33987123 pmcpmc8112096 doi1012890 2021_002434,0.0
linaclotide treatment refractory lower bowel manifestations systemic sclerosis background lower gastrointestinal gi tract involvement can affect 50 systemic sclerosis ssc patients may result malabsorption pseudoobstruction hospitalization death report experience linaclotide selective agonist guanylate cyclase c gcc ssc patients refractory lower gi diseasemethodswe performed analysis patients seen johns hopkins scleroderma center identified patients prescribed linaclotide refractory lower gi manifestations patients clinical data collected longitudinal database linaclotide responders medication least 12 months documented effectiveness treating physicianresultsthirtyone patients ssc treated linaclotide time linaclotide initiation 23 patients 74 classified severe gi disease defined recurrent pseudoobstruction malabsorption need artificial nutrition medsger gi severity score 3 majority patients 903 28 31 treatment response three patients 97 reported ineffectiveness intolerable side effects lowdose linaclotide 145 mcg daily used 18 patients effective 94 highdose therapy 145 mcg daily effective 11 13 patients 85 common side effects diarrhea cramping bloating 11 31 35 ineffectiveness cost abdominal pain complaints cited among discontinued therapyconclusionlinaclotide welltolerated efficacious prosecretory promotility agent can used manage refractory lower gi manifestations ssc found lowdose linaclotide effective option may better tolerated though subset patients may require high dose regimens,0.0
impact natalizumab quality life realworld cohort patients multiple sclerosis results ms paths mult scler j exp transl clin 2021 apr 15 7 2 20552173211004634 doi 101177 20552173211004634 ecollection 2021 aprjunabstractbackground optimizing multiple sclerosis treatment warrants understanding changes physical mental social healthobjective assess impact natalizumab quality life neurological disorders neuroqol scoresmethods annualized change tscores likelihood 5point improvement baseline calculated neuroqol domain natalizumab initiation comparisons ocrelizumabtreated patients conducted propensity score weighting adjustment relevant comedications year drugyear interactionresults among 164 natalizumab patients analyzed 8 12 neuroqol domains improved significantly greater improvement patients abnormal baseline neuroqol subgroup comparison natalizumabtreated n 145 ocrelizumabtreated n 520 patients significant improvement occurred 9 12 4 12 domains respectively difference groups statistically significant positive affect wellbeing p 002 sleep p 0003 satisfaction social roles activities sra p 003 overall population emotional behavioral dyscontrol p 001 participation sra p 00001 satisfaction sra p 002 patients abnormal baseline neuroqolconclusions natalizumab can produce clinically meaningful improvements mental social health improvements unlikely primarily driven expectation bias magnitude exceeded improvements another highefficacy therapy ocrelizumabpmid33948221 pmcpmc8053767 doi101177 20552173211004634,0.0
clinical pharmacogenomics action design assessment implementation novel pharmacogenetic panel supporting drug selection diseases central nervous system cns background pharmacogenomics describes link gene variations polymorphisms drug responses view implementation precision medicine personalized healthcare pharmacogenetic tests recently introduced clinical practice however translational aspects tests limited due lack robust populationbased evidencematerialsin paper present novel pharmacogenetic panel idna genomicspgxcns pgxcns consisting 24 single nucleotide polymorphisms snps 13 genes involved signaling metabolism 28 approved drugs currently administered treat diseases central nervous system cns tested pgxcns panel 501 patientderived dna samples southeastern european population applied biostatistical analyses pharmacogenetic associations involving drug selection dosing risk adverse drug events ades resultsresults reveal occurrences snp sample strong correlation european population nonlinear principal component analysis strongly indicates cooccurrences certain variants metabolization efficiency poor intermediate extensive ultrarapid frequency clinical useful pharmacogenetic associations population drug relevance also described along four exemplar clinical cases illustrating strong potential pgxcns panel companion diagnostic assay noted pharmacogenetic associations involving copy number variations cnvs hla gene included analysisconclusionsoverall results illustrate pgxcns panel valuable tool supporting therapeutic medical decisions urging broad clinical implementation,0.0
central nervous system barriers impact distribution expression inos arginase1 infiltrating macrophages neuroinflammation front immunol 2021 apr 15 12666961 doi 103389 fimmu2021666961 ecollection 2021abstractin multiple sclerosis ms neuroinflammatory diseases monocytederived cells mocs traffic distinct central nervous system cns barriers gain access organ parenchyma exerting detrimental beneficial functions mocs acquire different functional commitments cns invasion remains however unclear thus hindering design ms treatments specifically blocking detrimental moc actions clarify issue investigated distribution inos+ proinflammatory arginase1+ antiinflammatory mocs distinct border regions cns mouse model ms interestingly mocs within perivascular parenchymal spaces displayed predominant proinflammatory phenotype compared mocs accumulating leptomeninges intraventricular choroid plexus chp furthermore vitro model observe general ability functionallypolarized mocs migrate chp epithelial barrier together indicating chp potential cns entry polarization site mocs thus pro antiinflammatory mocs differentially accumulate distinct cns barriers reaching parenchyma mechanism phenotype acquisition remains undefined shedding light process observed endothelial bbb epithelial chp cns barrier cells can directly regulate transcription nos2 coding inos arg1 coding arginase1 interacting mocs specifically tnf+ifn stimulated bbb cells induced nos2 expression mocs il1 driven activation endothelial bbb cells led significant upregulation arg1 mocs supporting latter finding less proinflammatory mocs found nearby il1r1+ vessels mouse spinal cord upon neuroinflammation taken together data indicate differential distribution pro antiinflammatory mocs cns borders highlight interaction mocs cns barriers can significantly affect functional activation cnsinvading mocs autoimmune inflammationpmid33936108 pmcpmc8082146 doi103389 fimmu2021666961,0.0
defining disease course tnfalpha blockersassociated multiple sclerosis j neuroimmunol 2021 feb 20 353577525 doi 101016 jjneuroim2021577525 online ahead printabstracttumour necrosis factor alpha tnf blockers common effective treatments several autoimmune diseases can associated neuroinflammatory events describe disease course ten patients developed cns demyelinating events exposed tnf blockers divided two groups eight patients relapsing multiple sclerosis two isolated optic neuritis cohort tnf blockersassociated multiple sclerosis seem associated aggressive course can managed msspecific dmts chosen considering clinical course concomitant autoimmune disease findings need confirmation larger cohorts characterize disease course tnf blockersassociated multiple sclerosispmid33647875 doi101016 jjneuroim2021577525,1.0
covid19 hhv6 mog antibody perfect storm j neuroimmunol 2021 feb 12 353577521 doi 101016 jjneuroim2021577521 online ahead printabstractbackground serious neurological complications sarscov2 increasingly recognizedcase report novel case hhv6 myelitis parainfectious mogigg setting covid19induced lymphopenia hypogammaglobulinemia patient experienced complete neurological recovery gancyclovir high dose corticosteroids plasma exchange knowledge first case hhv6 reactivation central nervous system setting covid19 infection first case mogigg myelitis setting sarscov2 hhv6 coinfectionconclusion patients neurological manifestations setting covid19related immunodeficiency tested opportunistic infections including hhv6 viral infection known trigger mogigg therefore antibody checked patients sarscov2 associated demyelinationpmid33607505 doi101016 jjneuroim2021577521,0.0
circulating interleukins risk multiple sclerosis mendelian randomization study front immunol 2021 apr 15 12647588 doi 103389 fimmu2021647588 ecollection 2021abstractbackground previous research implicated critical roles systemic inflammation development multiple sclerosis ms causal relationship interleukins ils ms fully elucidatedobjective study applied mendelian randomization mr approaches address causal associations genetically determined circulating levels ils risk msmethods genetic instruments circulating il1 receptor antagonist il1ra il2 receptor subunit il2r il6 il16 il17 il18 obtained recently published genomewide association studies gwas summarylevel data ms obtained international multiple sclerosis genetics consortium mr analyses performed using r software version 361 r foundation twosamplemr packageresults genetic predisposition higher circulating levels il2r significantly associated ms risk odds ratio 122 95 confidence interval ci 112132 p 0001 per one standard deviation increase circulating il2r levels suggestive association circulating il1ra ms risk 094 95 ci 088099 p 0027 ils associated outcomeconclusion results indicated circulating il2r causally associated risk mspmid33936066 pmcpmc8081970 doi103389 fimmu2021647588,0.0
smoking alcohol opioids effect coronary microcirculation update overview abstractsmoking heavy alcohol drinking drug abuse detrimental lifestyle factors leading loss million years healthy life annually one major health complications caused substances development cardiovascular diseases cvd accounts significant proportion substanceinduced death smoking excessive alcohol consumption related higher risk acute myocardial infarction similarly opioid addiction one commonly used substances worldwide associated cardiac events ischemia myocardial infarction mi supported many studies coronary artery disease cad considered major cause substanceinduced cardiac events nonetheless last three decades growing body evidence indicates significant proportion substanceinduced cardiac ischemia mi cases manifest signs cad absence cad coronary microvascular dysfunction believed main underlying reason cvd date comprehensive literature reviews published clinicopathology cad caused smoking opioids well macrovascular pathological features alcoholic cardiomyopathy however best knowledge review article impact substances coronary microvascular network therefore present review will focus current understanding pathophysiological alterations coronary microcirculation triggered smoking alcohol opioids,0.0
orthopedic surgeryinduced cognitive dysfunction mediated cx3cl1 r1 signaling background postoperative pain common phenomenon surgery closely associated development postoperative cognitive dysfunction pocd persistent pain systemic inflammation caused surgery suggested key factors development pocd fractalkine cx3cl1 receptor cx3c chemokine receptor 1 cx3cr1 known play key role pain inflammation signaling pathways recent studies shown regulation cx3cr1 l1 signaling influences development various diseases including neuronal diseases determined whether cx3cr1 l1 signaling putative therapeutic target pocd mouse modelmethodsadult 911 weeks male mice treated neutralizing antibody block cx3cr1 l1 signaling surgery inflammatory behavioral responses including pain assessed postoperatively also cx3cr1 mrna level assessed hippocampal astrocyte activation mao b expression gaba expression assessed 2 days surgery following neutralizing antibody administrationresultsthe behavioral response indicated cognitive dysfunction development pain surgery group compared control group also increased levels proinflammatory cytokines cx3cr1 mrna observed surgery group addition increased levels gaba increased mao b expression observed reactive astrocytes surgery group responses attenuated neutralizing antibody administrationconclusionsincreased cx3cr1 surgery necessary sufficient induce cognitive dysfunction cx3cr1 important target therapeutic strategies prevent development pocd,0.0
interferoninduced pulmonary arterial hypertension approach diagnosis clinical monitoring jacc case rep 2021 apr 14 3 7 10381043 doi 101016 jjaccas202102005 ecollection 2021 jul 7abstracta 48yearold woman receiving longterm interferon 8 years multiple sclerosis developed druginduced world health organization group pulmonary arterial hypertension triple therapy pulmonary arterial hypertension suspension interferon led improvement highrisk lowrisk state improvement exercise hemodynamics including vascular distensibility right ventriclepulmonary artery coupling level difficulty advanced pmid34317680 pmcpmc8311374 doi101016 jjaccas202102005,0.0
mechanism action antigen processing independent t cell epitopes designed immunotherapy autoimmune diseases front immunol 2021 apr 14 12654201 doi 103389 fimmu2021654201 ecollection 2021abstractimmunotherapy antigenprocessing independent t cell epitopes apitopes targeting autoreactive cd4+ t cells translated clinic shown modulate progression graves disease multiple sclerosis model apitope ac19 4y renders antigenspecific t cells anergic repeated administration induces tr1 foxp3+ regulatory cells address cd4+ t cell epitopes designed apitopes induce tolerance define antigen presenting cells target vivo furthermore reveal impact treatment apitopes cd4+ t cell signaling generation il10secreting regulatory cells systemic migration cells taken together findings reveal apitopes induce tolerance thereby mediate antigenspecific immunotherapy autoimmune diseasespmid33936079 pmcpmc8079784 doi103389 fimmu2021654201,0.0
human alphasynuclein overexpressing mbp29 mice mimic functional structural hallmarks cerebellar subtype multiple system atrophy abstractmultiple system atrophy msa rare fatal atypical parkinsonian disorder prototypical pathological hallmark oligodendroglial cytoplasmic inclusions gcis containing alphasynuclein syn currently two msa phenotypes classified parkinsonian msap cerebellar subtype msac clinically characterized predominant parkinsonism cerebellar ataxia respectively previous studies shown transgenic msa mouse model overexpressing human syn controlled oligodendroglial myelin basic protein mbp promoter mbp29hsyn mice mirrors crucial characteristics msap subtype however remains elusive whether model recapitulates important features msacrelated phenotype first examined msacassociated cerebellar pathology using human postmortem tissue msac patients controls observed prototypical gci pathology preserved number oligodendrocytes cerebellar white matter cbw accompanied severe myelin deficit microgliosis profound loss purkinje cells secondly phenotypically characterized mbp29hsyn mice using dual approach structural analysis hindbrain functional assessment gait matching neuropathological features msac gci pathology within cbw mbp29hsyn mice accompanied severe myelin deficit despite increased number oligodendrocytes high number myeloid cells even early disease stage intriguingly mbp29hsyn mice developed significant loss purkinje cells advanced disease stage catwalk xt gait analysis revealed decreased walking speed increased stride length width hind paws addition less dual diagonal support observed toward dual lateral three paw support taken together widebased unsteady gait reflects cerebellar ataxia presumably linked cerebellar pathology mbp29hsyn mice conclusion present study strongly supports notion mbp29hsyn mouse model mimics important characteristics msac subtype providing powerful preclinical tool evaluating future interventional strategies,1.0
stigma psychological distress among pediatric participants fd mas alliance patient registry background stigma enacted internalized part illness experience many chronic conditions diseases found increase psychological distress lower selfesteem impact social engagement lowering quality life qol stigma among pediatric patients particular concern due potential impact identity formation using patient data online fd mas alliance patient registry fdmasapr study seeks 1 determine levels enacted selfstigma pediatric population fibrous dysplasia fd mccune albright syndrome mas patients 2 explore relationship stigma anxiety depressionmethodsthis cross sectional analysis deidentified selfreport data 18 pediatric patients key analytic variables include neuroqol stigma short form hospital anxiety depression scale hads diagnostic category craniofacial involvement select demographics sample means score distributions examined bivariate relationships stigma anxiety depression patients personal medical characteristics established analysis variance correlationresultscomposite stigma levels fd mas pediatric patients comparable children multiple sclerosis epilepsy muscular dystrophy selfstigma frequently reported enacted felt stigma patients indicated complete freedom either type stigma diagnosis significantly related selfstigma significant bivariate relationships found depression enacted felt selfstigma anxiety selfstigmaconclusionsthis study establishes illness experience pediatric patients fd mas impacted stigma suggests regularly screened stigma psychological distress supports integration clinical psychologists therapists regular patient care referral families advocacy organizations indicates rare disease patient registries can useful tool efforts improve qol patients,0.0
harnessing benefits neuroinflammation generation macrophages#x2f microglia prominent remyelinating properties ,1.0
upregulated endonuclease regnase1 suppresses osteoarthritis forming negative feedback loop catabolic signaling chondrocytes background ribonucleases rnases play central roles posttranscriptional regulation mrna stability preliminary results revealed endonuclease regnase1 specifically upregulated osteoarthritic chondrocytes herein explored possible functions regulatory mechanisms regnase1 mouse model osteoarthritis oa methodsthe expression target genes regnase1 identified microarray analysis primaryculture mouse articular chondrocytes experimental oa mice induced destabilization medial meniscus dmm function regnase1 dmminduced posttraumatic oa mice examined adenovirusmediated overexpression knockdown knee joint tissues also using regnase1 heterozygous knockout mice zc3h12a+ resultsamong rnases regnase1 exclusively upregulated chondrocytes stimulated oaassociated catabolic factors adenovirusmediated overexpression knockdown regnase1 alone joint tissues cause oalike changes however overexpression regnase1 joint tissues significantly ameliorated dmminduced posttraumatic oa cartilage destruction whereas knockdown genetic ablation regnase1 exacerbated dmminduced cartilage destruction mechanistic studies suggested regnase1 suppresses cartilage destruction modulating expression matrixdegrading enzymes chondrocytesconclusionour results collectively suggest upregulated regnase1 oa chondrocytes may function chondroprotective effector molecule oa pathogenesis forming negative feedback loop catabolic signals matrixdegrading enzyme expression oa chondrocytes,0.0
evaluation recognised systemic inflammatory biomarkers chronic suboptimal inflammation provides evidence inflammageing ifa multiple sclerosis ms abstractthe pathogenesis human demyelinating disorder multiple sclerosis ms involves loss immune tolerance selfneuroantigens deterioration immune tolerance linked inherent immune ageing immunosenescence isc previous work author confirmed presence isc ms moreover evidence verified prematurely aged immune system may change frequency profile ms altered decline immune tolerance immune ageing closely linked chronic systemic suboptimal inflammation termed inflammageing ifa disrupts efficiency immune tolerance varying dynamics isc includes accelerated changes immune system time therefore shifting deterioration immunological tolerance may evolve ms adverselyscheduled effects ifa isc however date collective proof ongoing ifa ms review addresses constraint provides systematic critique compelling evidence appraisal ifarelated biomarker studies support occurrence suboptimal inflammation ms findings justify work unequivocally demonstrate ifa ms provide additional insight complex pathology developing epidemiology disease,1.0
innate immunity impacts socialcognitive functioning people multiple sclerosis healthy individuals implications il1ra urinary immune markers brain behav immun health 2021 apr 14 14100254 doi 101016 jbbih2021100254 ecollection 2021 julabstractsocialcognitive difficulties can negatively impact interpersonal communication shared social experience meaningful relationships pilot investigation examined relationship socialcognitive functioning inflammatory markers people multiple sclerosis ms demographicallymatched healthy individuals additionally compared immune marker profile serum urinematched samples social cognitive functioning objectively assessed using awareness social inference test short tasits subjectively assessed using selfreports abilities emotion recognition emotional empathy cognitive theory mind people ms healthy individuals moderatetolarge negative relationships proinflammatory biomarkers serum il1 il17 tnf ip10 mip1 urine ip10 mip1 innate immune system socialcognitive functioning ms higher serum concentration antiinflammatory marker il1ra associated better socialcognitive functioning ie selfreported emotional empathy tasits sarcasm detection performance however mixed findings antiinflammatory serum markers il4 il10 overall findings indicate relationship proinflammatory cytokines socialcognitive abilities future studies may provide greater insight biologicallyderived inflammatory processes sickness behaviour connection social cognitionpmid34589763 pmcpmc8474509 doi101016 jbbih2021100254,0.0
natalizumab pharmacokinetics dynamics serum neurofilament patients multiple sclerosis front neurol 2021 apr 14 12650530 doi 103389 fneur2021650530 ecollection 2021abstractbackground natalizumab nat highefficacy treatment relapsing remitting multiple sclerosis rrms however associated increased risk progressive multifocal leukoencephalopathy sometimes requires treatment cessation risk returning disease activity aim study characterize pharmacokinetics dynamics well neurodestruction marker serum neurofilament light chain snfl patients rrms secondary progressive ms spms stopping nat correlation clinical data methods study 50 rrms 9 spms patients nat cessation included five rrms patients nat treatment holiday evaluated clinical radiological disease activity systemically assessed frequent exams nat stop free nat concentration cell bound nat 4integrin expression 4integrinreceptor saturation well immune cell frequencies measured 4 months nat withdrawal additionally snfl levels observed 12 months rrms 4 months spms patients results nat cessation associated return disease activity 38 rrms 33 spms patients within 12 7 months respectively concentration free cell bound nat well 4integrinreceptor saturation decreased rrms spms patients whereas 4integrin expression increased time nat induced increase lymphocytes subsets normalized nonsignificant drop nk th17 tcells counts detected rrms patients showed physiological snfl levels 8pg ml 1 month last nat infusion followup period snfl levels peaked 16fold linked return disease activity 19 37 rrms patients treatment holiday also associated return disease activity 4 5 patients increase snfl individual level conclusions demonstrate reversibility nat pharmacodynamic kinetic markers snfl levels associated recurrence disease activity can also serve early marker predict present onset clinical radiological disease activity individual levelpmid33935948 pmcpmc8079654 doi103389 fneur2021650530,0.0
correction epley manoeuvre posterior semicircular canal benign paroxysmal positional vertigo people multiple sclerosis protocol randomised controlled trial bmj open 2021 apr 14 11 4 1 doi 101136 bmjopen2020046510corr1no abstractpmid33853811 doi101136 bmjopen2020046510corr1,0.0
phase doseescalation oncology trials sequential multiple schedules background conventional methods phase doseescalation trials oncology based single treatment schedule recently however multiple schedules frequently investigated trialmethodshere consider sequential phase trials trial proceeds new schedule eg daily weekly dosing dose escalation another schedule completed aim utilize information completed ongoing schedules inform decisions dose level next dose cohort purpose adapted timetoevent pharmacokinetics titepk model originally developed simultaneous investigation multiple schedules titepk integrates information multiple schedules using pharmacokinetics pk modelresultsin simulation study developed approach compared bridging continual reassessment method bayesian logistic regression model using metaanalyticpredictive prior titepk results better performance comparators terms recommending acceptable dose avoiding overly toxic doses sequential phase trials scenarios considered furthermore better performance titepk achieved requiring similar number patients simulated trials scenarios involving one schedule titepk displays similar performance alternatives terms acceptable dose recommendations r stan code implementation illustrative sequential phase trial example oncology publicly available https githubcom gunhanb titepk_sequential conclusionin phase oncology trials sequential multiple schedules use relevant information great importance trials adapted titepk combines information using pk principles recommended,0.0
emerging genetic complexity rare genetic variants neurodegenerative brain diseases abstractknowledge molecular etiology neurodegenerative brain diseases nbd substantially increased past three decades early genetic studies nbd families identified rare highly penetrant deleterious mutations causal genes segregate disease large genomewide association studies uncovered common genetic variants influenced disease risk major developments nextgeneration sequencing ngs technologies accelerated gene discoveries unprecedented rate revealed novel pathways underlying nbd pathogenesis ngs technology exposed large numbers rare genetic variants uncertain significance vus coding regions highlighting genetic complexity nbd since experimental studies coding rare vus largely lacking potential contributions vus nbd etiology remain unknown review summarize novel findings nbd genetic etiology driven ngs impact rare vus nbd etiology consider different mechanisms rare vus can act influence nbd pathophysiology discuss better understanding rare vus instrumental deriving novel insights molecular complexity heterogeneity nbd new knowledge might open avenues effective personalized therapies,0.0
mesenchymal stem stromal cellbased therapy mechanism systemic safety biodistribution precision clinical applications abstractmesenchymal stem stromal cells mscs promising resource cellbased therapy high immunomodulation ability tropism towards inflamed injured tissues easy access isolation currently 1200 registered msc clinical trials globally however lack standardized methods characterize cell safety efficacy biodistribution dramatically hinders progress msc utility clinical practice review summarize current state mscbased cell therapy focusing systemic safety biodistribution mscs mscassociated risks tumor initiation promotion underlying mechanisms risks discussed addition msc biodistribution methodology pharmacokinetics pharmacodynamics cell therapies addressed better understanding systemic safety biodistribution mscs will facilitate future clinical applications precision medicine using stem cells,0.0
composite lymphoma tcell rich histiocyterich diffuse large bcell lymphoma nodular lymphocyte predominant hodgkin lymphoma case report background composite lymphoma rare entity two distinct subtypes lymphoma coexist within single organ tissuecase presentationwe report new case 67yearold caucasian male patient presented fatigue weakness weight loss polyuria also epigastric left lumbar pain enlarged spleen enlarged left axillary lymph node examination relevant medical familial historya biopsy node showed appearance tcell rich histiocyterich diffuse large bcell lymphoma nodular lymphocyte predominant hodgkin lymphomathe patient initially treated adriamycin doxorubicin bleomycin vinblastine dacarbazine chemotherapy regimen switched rituximab cyclophosphamide doxorubicin vincristine prednisone regimenduring therapy regression noticed especially size splenic enlargement however patient died 2 months completing regimenconclusioncomposite lymphomas continue studied also treatment still debatable type efficacy outcomes,0.0
lysophosphatidic acid lpa antibody 504b3 engagement detected interferometry identifies offtarget binding background lysophosphatidic acid lpa bioactive lysophospholipid acts six cognate g proteincoupled receptors family lysophospholipids already produced medicines eg sphingosine 1phosphate pursued lpa use specific antibodies reduce ligand availabilitymethodsthe binding properties commercially available reportedly specific monoclonal lpa antibody named 504b3 related clinical candidate lpathomab lt3015 reexamined using free solution assay fsa measured compensated interferometric reader cir resultsmeasurement 504b3 binding properties fsacir approach revealed similar binding affinities 504b3 lpa well nonlpa lipids phosphatidic acid pa lysophosphatidylcholine lpc conclusionsantibody binding specificity sensitivity particularly involving lipid ligands can assessed solution without labels using fsacir findings affect interpretations current past basic clinical studies employing 504b3 related antilpa antibodies,0.0
evaluation patients optic disc edema retrospective study north clin istanb 2021 apr 14 8 3 280285 doi 1014744 nci202025483 ecollection 2021abstractobjective optic disc edema among major problems neuroophthalmology clinics encounter intended analyze patients optic disc edema articlemethods data related main complaint associated systemic disease visual acuity characteristics optic disc swelling ocular findings topical systemic drugs treatment methods followup examination related data patients obtained retrospectivelyresults 77 female 23 male patients study optic disc edema detected bilaterally 65 patients unilaterally 35 patients duration symptoms first application 19821718 090 days systemic disorders 74 patients diabetes mellitus 11 patients hypertension four patients coronary artery disease three patients urticaria two patients lymphoma one multiple sclerosis one patient mastoiditis one patient scleroderma one pregnancy two patients detected 93 patients additional ocular findings 2 uveitis 1 corneal dystrophy 1 keratoconus 1 cataract 1 previous cataract surgery 1 peripheral retinal degenerations major etiology optic disc edema idiopathic intracranial hypertension detected 44 patients patients bilateral optic disc edema observed 43 patients given oral acetazolamide one patient oral topiramateconclusion presence optic nerve edema absolutely evaluated patients presenting symptoms vision loss increased intracranial pressure early diagnosis fundoscopic examination may increase visual acuity patientspmid34222810 pmcpmc8240241 doi1014744 nci202025483,0.0
myelin repair animal models humans front cell neurosci 2021 apr 14 15604865 doi 103389 fncel2021604865 ecollection 2021abstractit widely thought brain repair occur myelin regeneration provides clear evidence contrary spontaneous remyelination may occur injury multiple sclerosis ms however efficiency remyelination varies considerably ms patients lesions patient myelin repair essential optimal functional recovery profound understanding cells mechanisms involved process required development new therapeutic strategies review describe animal models modern cell tracing imaging methods helped identify cell types involved myelin regeneration addition oligodendrocyte progenitor cells identified 1990s principal source remyelinating cells central nervous system cns cell populations including subventricular zonederived neural progenitors schwann cells even spared mature oligodendrocytes recently emerged potential contributors cns remyelination will also highlight conditions known limit endogenous repair aging chronic inflammation production extracellular matrix proteins role astrocytes microglia processes finally will present discrepancies observations humans rodents discussing relationship findings experimental models myelin repair humans considerations particularly important therapeutic standpointpmid33935649 pmcpmc8079744 doi103389 fncel2021604865,1.0
harnessing benefits neuroinflammation generation macrophages microglia prominent remyelinating properties excessive inflammation within cns injurious immune response also required regeneration macrophages microglia adopt different properties depending microenvironment exposure il4 il13 used elicit repair unexpectedly lpsexposed macrophages microglia killed neural cells culture addition lps il4 il13treated macrophages microglia profoundly elevated il10 repair metabolites heparin binding epidermal growth factor trophic factor antioxidants matrixremodeling proteases c57bl 6 female mice generation m lps il4 il13 macrophages required tlr4 myd88 signaling downstream activation phosphatidylinositol3 kinase mtor map kinases convergence phosphocreb stat6 nfe2 following mouse spinal cord demyelination local lps il4 il13 deposition markedly increased lesional phagocytic macrophages microglia lactate heparin binding epidermal growth factor matrix remodeling oligodendrogenesis remyelination data show prominent reparative state macrophages microglia generated unexpected integration pro antiinflammatory activation cues results translational potential lps il4 il13 mixture locally applied focal cns injury enhance neural regeneration recoverysignificance statement combination lps regulatory il4 il13 signaling macrophages microglia produces previously unknown particularly reparative phenotype devoid proinflammatory neurotoxic features local administration lps il4 il13 spinal cord lesion elicits profound oligodendrogenesis remyelination careful use lps il4 il13 mixture harness known benefits neuroinflammation enable repair neurologic insults,1.0
development tibial experimental nonunion model rats background many nonunion animal models developed explore problems surrounding fracture healing however existing models perfect satisfy nonunion studies study aimed make nonunion model tibia rats cauterization posterior 2 mm sides fracture end open osteotomy tibia fixing fractured tibia kirschner wire 08 mm diametermethodsfor study 96 female adult spraguedawley sd rats used rats underwent surgery produce tibial open fracture fixed 08mm diameter kirschner wire 48 rats periosteum proximal distal fracture end cauterizedresultsat 2 4 6 8 weeks surgery radiological histological analysis showed typical physiological healing control group healing rate 100 6 weeks nonunion group characterized resorption fracture ends callus formations bridging callus formation healing rate 0 8 weeksconclusionsthis method represents reproducible model create atrophic nonunions model provides new option studying basic healing mechanisms evaluating new therapies bone regeneration treatment nonunions,0.0
experimental infection hookworm necator americanus associated stable gut microbial diversity human volunteers relapsing multiple sclerosis background helminthassociated changes gut microbiota composition hypothesised contribute immunesuppressive properties parasitic worms multiple sclerosis immunemediated autoimmune disease central nervous system whose pathophysiology linked imbalances gut microbial communitiesresultsin present study investigated first time qualitative quantitative changes faecal bacterial composition human volunteers remitting multiple sclerosis rms prior following experimental infection human hookworm necator americanus n+ following anthelmintic treatment compared findings data obtained cohort rms patients subjected placebo treatment pbo bacterial 16s rrna highthroughput sequencing data revealed significantly decreased alpha diversity faecal microbiota pbo compared n+ subjects course trial additionally observed significant differences abundances several bacterial taxa putative immunemodulatory functions study cohorts parabacteroides significantly expanded faecal microbiota n+ individuals clinical radiological relapses recorded end trialconclusionsoverall data lend support hypothesis contributory role parasiteassociated alterations gut microbial composition immunemodulatory properties hookworm parasites,0.0
circ_0116061 regulated proliferation apoptosis inflammation osteoarthritis chondrocytes regulating mir200b3p smurf2 axis background circular rna circrna shown associated osteoarthritis oa progression circ_0116061 found highly expressed oa cartilage tissues role mechanism oa progression remain unclearmethodsexpression levels circ_0116061 microrna mir 200b5p smad ubiquitin regulatory factor 2 smurf2 detected using quantitative realtime pcr proliferation apoptosis cells measured using cell counting kit 8 cck8 assay colony formation assay flow cytometry furthermore protein levels proliferationrelated marker apoptosisrelated markers inflammatory factors smurf2 tested using western blot wb analysis addition interaction mir200b3p circ_0116061 smurf2 examined using dualluciferase reporter assay biotinlabeled rna pulldown assayresultscirc_0116061 smurf2 highly expressed mir200b3p lowly expressed oa cartilage tissues knockdown circ_0116061 promote proliferation inhibit apoptosis inflammation oa chondrocytes mir200b3p sponged circ_0116061 inhibitor reverse regulation circ_0116061 silencing biological functions oa chondrocytes smurf2 target mir200b3p expression positively regulated circ_0116061 silencing smurf2 also enhance proliferation suppress apoptosis inflammation oa chondrocytes furthermore regulation circ_0116061 silencing biological functions oa chondrocytes also reversed smurf2 overexpressionconclusionour data showed circ_0116061 might regulate mir200b3p smurf2 axis promote progression oa,0.0
serum resolvin e1 levels relationship thyroid autoimmunity hashimotos thyroiditis preliminary study background omega3 polyunsaturated fatty acids pufas produce lipid mediators antiinflammatory proresolution properties including resolvins purpose study detect serum resolvin e1 rve1 levels hashimotos thyroiditis ht patients healthy controls hcs evaluate relationship rve1 thyroid autoimmunitymethodsa total 57 participants recruited including 30 untreated ht patients 27 age sexmatched hcs levels rve1 serum measured via enzymelinked immunosorbent assay elisa electrochemiluminescence immunoassay used measurement thyroidstimulating hormone tsh total t4 tt4 tt3 free t4 ft4 ft3 antithyroid peroxidase antibody tpoab antithyroglobulin antibody tgab levels hemogram tests routine biochemical analyses performed sampleresultsthe serum level rve1 ht patients 2409 15763438 pg ml significantly lower healthy controls 2851 20765123 pg ml p 0027 rve1 levels showed downward trend increasing tgab levels p trend 0001 multivariable ordinal logistic regression analysis showed rve1 levels negatively correlated increasing tgab levels unadjusted 09446 95 ci 0911109782 p 0002 adjusted models 09380 95 ci 0896709811 p 0005 conclusionsdecreased rve1 levels might sign ht associated inflammatory resolution dysfunction rve1 may serve protective factor increased tgab levels,0.0
baricitinib ameliorates experimental autoimmune encephalomyelitis modulating janus kinase signal transducer activator transcription signaling pathway front immunol 2021 apr 13 12650708 doi 103389 fimmu2021650708 ecollection 2021abstractexperimental autoimmune encephalomyelitis eae animal model multiple sclerosis ms cd4+ t cellmediated autoimmune disease janus kinase jak signal transducer activator transcription stat pathway recognized major mechanism regulates differentiation function t helper th 1 th17 cells recognized pivotal effector cells responsible development eae used baricitinib jak 1 2 inhibitor investigate therapeutic efficacy inhibiting jak stat pathway eae mice results showed baricitinib significantly delayed onset time decreased severity clinical symptoms shortened duration eae alleviated demyelination immune cell infiltration spinal cord addition baricitinib treatment downregulated proportion interferon+cd4+ th1 interleukin17+cd4+ th17 cells decreased levels retinoic acidrelated orphan receptor t tbet mrna inhibited lymphocyte proliferation decreased expression proinflammatory cytokines chemokines spleen mice eae furthermore results showed role baricitinib suppressing phosphorylation stats 1 3 4 spleen eae mice therefore study demonstrates baricitinib potentially alleviate inflammation mice eae may promising candidate treating mspmid33927721 pmcpmc8076548 doi103389 fimmu2021650708,1.0
plasma membrane integrity implications health disease abstractplasma membrane integrity essential cellular homeostasis vivo cells experience plasma membrane damage multitude stressors extra intracellular environment avoid lethal consequences cells equipped repair pathways restore membrane integrity assess plasma membrane damage repair wholebody perspective highlight role tissuespecific stressors health disease examine membrane repair pathways across diverse cell types furthermore outline impact genetic environmental factors plasma membrane integrity contribute disease pathogenesis different tissues,0.0
adiponectinmimetic novel nonapeptide rescues aberrant neuronal metabolicassociated memory deficits alzheimers disease background recently researchers reported brain metabolic disorders implicated alzheimers disease ad progressive devastating incurable neurodegenerative disease hence novel therapeutic approaches urgently needed explore potential novel therapeutic targets agents treatment ad neuronal adiponectin receptor 1 adipor1 emerging potential target intervention metabolicassociated ad aimed validate hypothesis explore indepth therapeutic effects osmotinderived adiponectinmimetic novel nonapeptide ospep metabolicassociated admethodswe used ospep dosage regimen 5 g g ip alternating days 45 days app ps1 amyloid oligomerinjected transgenic adiponectin knockout adipo adipor1 knockdown mice behavioral studies brain tissues subjected biochemical immunohistochemical analyses separate cohorts mice electrophysiolocal golgi staining experiments performed validate vivo studies used human app swedish swe indiana ind overexpressing neuroblastoma shsy5y cells subjected knockdown adipor1 apmk sirnas treated ospep conditions per mechanistic approach proceeded perform biochemical analysesresultsour vitro vivo results show ospep good safety neuroprotection profiles crosses bloodbrain barrier found reduced levels neuronal adipor1 human ad brain tissue ospep stimulates adipor1 downstream target ampactivated protein kinase ampk signaling ad adipo mice mechanistically vivo vitro studies ospep rescued aberrant neuronal metabolism reducing neuronal insulin resistance activated downstream insulin signaling regulation adipor1 ampk signaling consequently improve memory functions ad adipo mice associated improved synaptic function longterm potentiation via adipor1dependent mechanismconclusionour findings show ospep activates adipor1 ampk signaling regulates neuronal insulin resistance insulin signaling subsequently rescues memory deficits ad adiponectindeficient models taken together results indicate ospep adiponectinmimetic novel nonapeptide valuable promising potential therapeutic candidate treat aberrant brain metabolism associated ad neurodegenerative diseases,0.0
disrupted lipid metabolism multiple sclerosis role liver x receptors front endocrinol lausanne 2021 apr 13 12639757 doi 103389 fendo2021639757 ecollection 2021abstractmultiple sclerosis ms chronic neurological disease driven autoimmune inflammatory neurodegenerative processes leading neuronal demyelination subsequent degeneration systemic lipid metabolism disturbed people ms lipid metabolic pathways crucial protective process remyelination lipidactivated transcription factors liver x receptors lxrs important integrators lipid metabolism immunity consequently strong interest targeting receptors number metabolic inflammatory diseases including ms reviewed evidence involvement lxrdriven lipid metabolism dysfunction peripheral brainresident immune cells ms focusing human studies relapsing remitting progressive phases disease discussed finally discuss therapeutic potential modulating activity receptors existing pharmacological agents highlight important areas future researchpmid33927692 pmcpmc8076792 doi103389 fendo2021639757,1.0
4ebp2dependent translation parvalbumin neurons controls epileptic seizure threshold proc natl acad sci u s 2021 apr 13 118 15 e2025522118 doi 101073 pnas2025522118abstractthe mechanistic mammalian target rapamycin complex 1 mtorc1 integrates multiple signals regulate critical cellular processes mrna translation lipid biogenesis autophagy germline somatic mutations mtor genes upstream mtorc1 pten tsc1 2 akt3 pik3ca components gator1 kicstor complexes associated various epileptic disorders increased mtorc1 activity linked pathophysiology epilepsy humans animal models mtorc1 inhibition suppresses epileptogenesis humans tuberous sclerosis animal models elevated mtorc1 activity however role mtorc1dependent translation neuronal cell types mediating effect enhanced mtorc1 activity seizures remain unknown eukaryotic translation initiation factor 4ebinding protein 1 4ebp1 2 4ebp2 translational repressors downstream mtorc1 show ablation 4ebp2 4ebp1 mice increases sensitivity pentylenetetrazole ptz kainic acid ka induced seizures demonstrate deletion 4ebp2 inhibitory excitatory neurons causes increase susceptibility ptzinduced seizures moreover mice lacking 4ebp2 parvalbumin somatostatin vip inhibitory neurons exhibit lowered threshold seizure induction reduced number parvalbumin neurons mouse model harboring human pik3ca mutation enhances activity pi3kakt pathway pik3ca h1047rpvalb selectively parvalbumin neurons shows susceptibility ptzinduced seizures data identify 4ebp2 regulator epileptogenesis highlight central role increased mtorc1dependent translation parvalbumin neurons pathophysiology epilepsypmid33876772 doi101073 pnas2025522118,0.0
improved cortical activity reduced gait asymmetry poststroke selfpaced walking rehabilitation background patients gait impairment due neurological disorders body weightsupported treadmill training bwstt widely used gait rehabilitation conventional passive treadmill runs constant speed however level patient engagement cortical activity decreased compared gait training ground increase level cognitive engagement brain activity gait rehabilitation selfpaced active treadmill introduced allow patients actively control walking speed overground walkingmethodsto validate effects selfpaced treadmill walking cortical activities paper presents clinical test stroke survivors hypothesized cortical activities affected side brain also increase active walking patients match target walking speed affected lower limbs thus asymmetric gait patterns limping hobbling might also decrease active walkingresultsalthough clinical test conducted short period patients showed higher cognitive engagement improved brain activities assessed electroencephalography eeg decreased gait asymmetry selfpaced treadmill expected increases spectral power low bands prefrontal cortex pfc premotor cortex pmc supramarginal gyrus sg found possibly related processing sensory data planning voluntary movements addition changes cortical activities also found affected lower limbs swing phase since treadmill controller tracked swing speed leg control walking speed results imply subjects made substantial effort control affected legs swing phase match target walking speedconclusionsthe patients also showed reduced gait asymmetry patterns based results selfpaced gait training system potential train symmetric gait promote related cortical activities stroketrial registration applicable,0.0
accuracy patientperceived usability acceptance two symptom checkers ada rheport rheumatology interim results randomized controlled crossover trial background timely diagnosis treatment essential effective management inflammatory rheumatic diseases irds symptom checkers scs promise accelerate diagnosis reduce misdiagnoses guide patients effectively health care system although scs increasingly used exists little supporting evidenceobjectiveto assess diagnostic accuracy patientperceived usability acceptance two scs 1 ada 2 rheportmethodspatients newly presenting german secondary rheumatology outpatient clinic randomly assigned 11 ratio complete ada rheport consecutively respective scs prospective nonblinded controlled randomized crossover trial primary outcome accuracy scs regarding diagnosis ird compared physicians diagnosis gold standard secondary outcomes patientperceived usability acceptance time complete scresultsin interim analysis first 164 patients completed study analyzed 329 54 164 study subjects diagnosed ird rheport showed sensitivity 537 specificity 518 irds adas top 1 d1 top 5 disease suggestions d5 showed sensitivity 426 537 specificity 636 545 concerning irds respectively correct diagnosis ird patients within ada d1 d5 suggestions 167 9 54 259 14 54 respectively median system usability scale sus score ada rheport 750 100 775 100 respectively median completion time ada rheport 70 85 min respectively sixtyfour percent 671 recommend using ada rheport friends patients respectivelyconclusionswhile scs well accepted among patients diagnostic accuracy limited datetrial registrationdrksde drks00017642 registered 23 july 2019,0.0
fgf fgfr pathways multiple sclerosis disease models cells 2021 apr 13 10 4 884 doi 103390 cells10040884abstractmultiple sclerosis ms chronic inflammatory neurodegenerative disease central nervous system cns affecting two million people worldwide ms oligodendrocytes myelin sheaths destroyed autoimmunemediated inflammation remyelination impaired recent investigations postmortem tissue suggest fibroblast growth factor fgf signaling may regulate inflammation myelination ms fgf2 expression seems correlate positively macrophages microglia negatively myelination fgf1 suggested promote remyelination myelin oligodendrocyte glycoprotein mog 3555induced experimental autoimmune encephalomyelitis eae systemic deletion fgf2 suggested fgf2 may promote remyelination specific deletion fgf receptors fgfrs oligodendrocytes eae model resulted decrease lymphocyte macrophage microglia infiltration well myelin axon degeneration effects mediated erk akt phosphorylation brainderived neurotrophic factor downregulation inhibitors remyelination first part review important pharmacotherapeutic principles ms will illustrated will review recent advances made fgf signaling ms thus will suggest application fgfr inhibitors currently used phase ii iii cancer trials therapeutic option reduce inflammation induce remyelination eae eventually mspmid33924474 doi103390 cells10040884,1.0
impaired atg16ldependent autophagy promotes renal interstitial fibrosis chronic renal graft dysfunction inducing endmt nfb signal pathway front immunol 2021 apr 13 12650424 doi 103389 fimmu2021650424 ecollection 2021abstractchronic renal graft dysfunction cad caused multiple factors including glomerular sclerosis inflammation interstitial fibrosis tubular atrophy ta however prominent elements cad ta studies confirmed endothelialmesenchymal transition endmt important source allograft ta characteristic endmt loss endothelial marker acquisition mesenchymal fibroblastic phenotypes autophagy intracellular degradation pathway regulated autophagyrelated proteins plays vital role many fibrotic conditions however whether autophagy contributes fibrosis renal allograft mechanism occurs still remains unclear autophagy related 16 like gene atg16l critical autophagyrelated gene arg necessary autophagosome formation first analyzed kidney transplant patient tissues gene expression omnibus geo datasets 60 transplant patients center recipients stable kidney function defined noncad group patients cad group histopathologically diagnosed cad results showed atg16l one significant differential arg less expressed cad group compared noncad group furthermore found less autophagosomes autolysosomes transplanted kidneys cad patients downregulation autophagy poor prognostic factor vitro found knockdown atg16l enhanced process endmt human renal glomerular endothelial cells hrgecs vivo changes endmt autophagic flux detected rat renal transplant models cad demonstrated occurrence endmt indicated abundance atg16l accompanied dynamic autophagic flux change along different stages kidney transplantation mechanistically knockdown atg16l specifically endothelial cells reduced nfb degradation excreted inflammatory cytokines il1 il6 tnf facilitate endmt conclusion atg16ldependent autophagic flux causing transplant showed progressive loss increase time inflammatory cytokines process promoted endmt thereby leading progression cad atg16l served negative regulator endmt development renal graft fibrosis autophagy can explored potential therapeutic target chronic renal graft dysfunctionpmid33927720 pmcpmc8076642 doi103389 fimmu2021650424,0.0
microglia specific drug targeting using natural products regulation redox imbalance neurodegeneration front pharmacol 2021 apr 13 12654489 doi 103389 fphar2021654489 ecollection 2021abstractmicroglia type innate immune cell brain regulates neurogenesis immunological surveillance redox imbalance cognitive behavioral changes normal pathological conditions like alzheimers parkinsons multiple sclerosis traumatic brain injury microglia produces wide variety cytokines maintain homeostasis also participates synaptic pruning regulation neurons overproduction phagocytosis neural precursor cells phenotypes microglia regulated local microenvironment neurons astrocytes via interaction soluble membranebound mediators case neuron degeneration observed acute chronic neurodegenerative diseases microglia gets released inhibitory effect neurons astrocytes showing activated phenotype either dual function microglia shows neuroprotective effect secreting growths factors heal neurons clears cell debris phagocytosis case moderate stimulus microglia starts releasing proinflammatory cytokines like tnf ifn reactive oxygen species ros nitric oxide increasing neuroinflammation redox imbalance brain chronic signals therefore pharmacological targeting microglia promising strategy regulation neuroinflammation redox imbalance oxidative stress neurodegenerative diseases studies present potentials natural products like curcumin resveratrol cannabidiol ginsenosides flavonoids sulforaphane suppress activation microglia natural products also proposed effective therapeutics regulate progression neurodegenerative diseases present review article intends explain molecular mechanisms functions microglia molecular dynamics microglia specific genes proteins like iba1 tmem119 neurodegeneration possible interventions curcumin resveratrol cannabidiol ginsenosides flavonoids sulforaphane microglia specific protein iba1 suggest possibility natural products mediated regulation microglia phenotypes functions control redox imbalance neuroinflammation management alzheimers parkinsons multiple sclerosis microgliamediated therapeuticspmid33927630 pmcpmc8076853 doi103389 fphar2021654489,1.0
costofillness studies rare diseases scoping review abstractobjectivethe aim scoping review overview costofillness studies conducted rare diseases methodswe searched papers published english pubmed january 2007 december 2018 selected costofillness studies rare diseases defined prevalence lower 5 per 10 000 cases studies selected one researcher verified second researcher methodological characteristics extracted develop narrative synthesis resultswe included 63 costofillness studies 42 rare diseases conducted 25 countries 9 systematic reviews studies 94 adopted prevalencebased estimation predominant design crosssectional bottomup approach four studies adopted incidencebased estimation studies used questionnaires patients caregivers collect resource utilisation data 67 although important number studies used databases registries source data 48 costs lost productivity nonmedical costs informal care costs included 68 60 43 studies respectivelyconclusionthis review found paucity costofillness studies rare diseases however analysis shows costofillness studies rare diseases feasible although main issue lack primary aggregated data often prevents reliable estimation economic burden,0.0
convergent discriminative validity frailvig index eq5d3l people cared primary health care background frailvig frailty index developed recently instrument multidimensional approach pragmatic purpose allows rapid efficient assessment degree frailty context clinical practice aim investigate convergent discriminative validity frailvig frailty index regard eq5d3l valuemethodswe carried crosssectional study two primary health care phc centres catalan institute health institut catal de la salut barcelona spain february 2017 january 2019 participants study people included home care programme study period exclusion criteria applied used eq5d3l measure healthrelated quality life hrqol frailvig index measure frailty trained phc nurses administered instruments facetoface assessments participants home usual care relationships instruments examined using pearsons correlation coefficient multiple linear regression analysesresultsfour hundred twelve participants included study frailvig score eq5d3l value negatively correlated r 0510 p 0001 nonfrail people reported substantially better hrqol people moderate severe frailty eq5d3l value declined significantly frailvig index score increasedconclusionsfrailvig index demonstrated convergent validity eq5d3l value discriminative validity optimal scores showed excellent capacity differentiate people better worse hrqol findings provide additional pieces evidence construct validity frailvig index,0.0
therapeutic potential immunomodulatory role coenzyme q10 analogues systemic autoimmune diseases antioxidants basel 2021 apr 13 10 4 600 doi 103390 antiox10040600abstractcoenzyme q10 coq10 mitochondrial electron carrier powerful lipophilic antioxidant located membranes plasma lipoproteins coq10 endogenously synthesized obtained diet raised interest therapeutic potential pathologies related mitochondrial dysfunction enhanced oxidative stress novel formulations solubilized coq10 stabilization reduced coq10 ubiquinol improved bioavailability efficacy synthetic analogues increased solubility idebenone accumulated selectively mitochondria mitoq also demonstrated promising properties coq10 shown beneficial effects autoimmune diseases leukocytes antiphospholipid syndrome aps patients exhibit oxidative perturbation closely related prothrombotic status vivo ubiquinol supplementation aps modulated overexpression inflammatory thrombotic riskmarkers mitochondrial abnormalities also contribute immune dysregulation organ damage systemic lupus erythematosus sle idebenone mitoq improved clinical immunological features lupuslike disease mice clinical trials experimental models demonstrated therapeutic role coq10 rheumatoid arthritis multiple sclerosis type 1 diabetes review summarizes effects coq10 analogs modulating processes involved autoimmune disorders highlighting potential therapeutic approaches patients immunemediated diseasespmid33924642 doi103390 antiox10040600,0.0
comprehensive analysis role hnrnp a1 function dysfunction pathogenesis neurodegenerative disease front mol biosci 2021 apr 12 8659610 doi 103389 fmolb2021659610 ecollection 2021abstractheterogeneous nuclear ribonucleoprotein a1 hnrnp a1 member hnrnp family conserved proteins involved rna transcription premrna splicing mrna transport protein translation microrna processing telomere maintenance regulation transcription factor activity hnrnp a1 ubiquitously yet differentially expressed many cell types due posttranslational modifications can vary molecular function plethora knowledge known function dysfunction hnrnp a1 diseases neurodegenerative disease eg cancer numerous studies amyotrophic lateral sclerosis frontotemporal lobar degeneration multiple sclerosis spinal muscular atrophy alzheimers disease huntingtons disease found dysregulation hnrnp a1 may contribute disease pathogenesis hnrnp a1 mechanistically contributes diseases whether mutations altered posttranslational modifications contribute pathogenesis however currently investigation aim comprehensive review first describe background hnrnp a1 including structure biological functions rna metabolism posttranslational modifications known modify function knowledge review describes influence hnrnp a1 neurodegenerative disease dysfunction may contribute pathogenesispmid33912591 pmcpmc8072284 doi103389 fmolb2021659610,0.0
epitopebased chickenderived novel antipad2 monoclonal antibodies inhibit citrullination j immunol res 2021 apr 12 20216659960 doi 101155 2021 6659960 ecollection 2021abstractthe aberrant upregulation protein arginine deiminase 2 pad2 catalyzed citrullination reported various autoimmune diseases rheumatoid arthritis multiple sclerosis several cancers currently antipad2 monoclonal antibodies mabs can inhibit citrullination reaction epitope 341ylnrgdrwiqdeiefgy357 examined antigenic site pad2 chickens immunized epitope generated mabs screened reactivity fulllength pad2 enzymelinked immunosorbent assay revealed six mabs screened phage display library crossreacted mouse pad2 kinetic analysis revealed mabs bound pad2 nanomolar range indicated strong binding results vitro citrullination inhibition assay revealed halfmaximal effective concentration values mabs inhibition histone benzoyllarginine ethyl ester citrullination range 675 nm supports strong inhibition capabilities alanine scanning epitope revealed peptide fragment 344rgdrwiqdeief355 responsible generating strong antibody responses inhibit pad2catalyzed citrullination reaction antibodies can aid understanding extracellular pad2 function treating diseases associated aberrant citrullinationpmid33937418 pmcpmc8055403 doi101155 2021 6659960,0.0
subclinical anterior optic pathway involvement early multiple sclerosis clinically isolated syndromes brain 2021 apr 8awaa458 doi 101093 brain awaa458 online ahead printabstractoptical coherence tomography oct gaining increasing relevance assessment patients multiple sclerosis converging evidence point view neuroretinal changes eyes without acute optic neuritis reflect inflammatory neurodegenerative processes taking place throughout cns present study aims exploring usefulness oct marker inflammation disease burden earliest phases disease thus cohort 150 consecutive patients underwent clinical neurophysiological brain mri assessment well lumbar puncture part diagnostic workup neurological episode suggestive inflammatory cns disorder among 32 patients another previous misdiagnosed episode present study patients also received visual pathway assessment oct visual evoked potentials visual acuity measurement csf inflammatory markers 17 cytokineschemokines extracellular vesicles myeloid origin dosage plasma neurofilaments subclinical optic nerve involvement frequently found clinically isolated syndromes visual evoked potentials 192 oct reveals ganglion cell layer asymmetries 68 patients retinal fibre layer asymmetries despite frequent 178 display poor specificity presence subclinical involvement associated greater disease burden second ganglion cell layer thinning reflects severity disease involvement even beyond anterior optic pathway fact ganglion cell layer eyes without evidence subclinical optic involvement correlated expanded disability status scale low contrast visual acuity disease duration brain lesion load presence gadolinium enhancing lesions abnormalities along motor somatosensory evoked potentials frequency csfspecific oligoclonal bands third inner nuclear layer thickens postacute 1137 months phase relapse phenomenon counteracted steroid treatment likewise longitudinal analysis 65 patients shows swelling transient returns normal values 1 year followup notwithstanding clinical mri serological csf markers disease activity considered study strictly associated one another none associated inner nuclear layer findings challenge current hypothesis inner nuclear layer acute phase marker inflammatory activity present study suggests instrumental evidence subclinical optic nerve involvement associated greater disease burden clinically isolated syndrome neuroretinal changes present since earliest phases disease yield important information regarding neurodegenerative inflammatory processes occurring cnspmid33829250 doi101093 brain awaa458,0.0
illumination molecular pathways multiple sclerosis lesions immune mechanism matrine treatment eae mouse model ms front immunol 2021 apr 12 12640778 doi 103389 fimmu2021640778 ecollection 2021abstractthe etiology multiple sclerosis ms clear treatment ms presents great challenge study aimed investigate pathogenesis potential therapeutic targets ms define target genes matrine quinolizidine alkaloid component derived root sophorae flavescens effectively suppressed experimental autoimmune encephalomyelitis eae animal model ms end gse108000 gene data set gene expression omnibus database included 7 chronic active ms lesions 10 control samples white matter analyzed differentially expressed genes degs x cell used analyze microenvironmental differences brain tissue samples ms patients including 64 types immune cells stromal cells biological functions enriched signaling pathways degs analyzed multiple approaches including go kegg gsea gsva results x cell showed significantly increased numbers immune cell populations ms lesions decreased erythrocytes megakaryocytes adipocytes keratinocytes endothelial cells th1 cells tregs gse108000 637 degs including 428 upregulated 209 downregulated genes potential target genes matrine predicted network pharmacology method traditional chinese medicine 12 key genes obtained cross analysis target genes matrine degs ms lesions finally confirmed rtpcr predicted expression genes brain tissues matrinetreated eae mice among genes 2 significantly downregulated 6 upregulated matrine treatment significance gene regulation investigated conclusion study defined several possible matrine target genes can elucidated mechanism s matrine action novel targets treatment mspmid33912166 pmcpmc8072148 doi103389 fimmu2021640778,0.0
msbase pregnancy neonatal outcomes women#39 s health registry ther adv neurol disord 2021 apr 12 1417562864211009104 doi 101177 17562864211009104 ecollection 2021abstractbackground family planning pregnancy decisions key considerations management women multiple sclerosis ms typically diagnosed ages 2040 years despite strong evidence base pregnancy harmful women ms many knowledge gaps remain include best management strategies pregnancy era highly effective diseasemodifying therapies dmt foetal risks associated dmt exposure utero relation breastfeeding knowledge base around use assisted reproductive technologies longterm impact pregnancy disease outcomes well impact longterm dmt use womens health cancer riskmethods describe new msbase pregnancy neonatal outcomes womens health registry provide rationale detailed description variables collected within registry together data acquisition detailsconclusion present paper will act reference document future studiespmid33912245 pmcpmc8047930 doi101177 17562864211009104,0.0
yoga older adults multimorbidity gentle years yoga trial study protocol randomised controlled trial background multimorbidity common older adults associated high levels illness burden healthcare expenditure evidence base manage older adults multimorbidity weak yoga might useful intervention potential improve healthrelated quality life physical functioning several medical conditions british wheel yogas gentle years yoga gyy programme developed specifically older adults including chronic medical conditions data pilot trial suggested feasibility using gyy population effectiveness costeffectiveness remain uncertainmethodsthis multisite individually randomised superiority trial embedded process evaluation economic analysis costeffectiveness trial will compare experimental strategy offering 12week gyy programme control strategy offer communitydwelling adults aged 65 multimorbidity defined two chronic conditions predefined list primary outcome healthrelated quality life measured using eq5d5l primary endpoint overall difference 12 months groups will continue able access usual care primary secondary community social services participants care providers yoga teachers will blinded allocated intervention outcome measures primarily selfreported analysis will follow intentiontotreat principlesdiscussionthis pragmatic randomised controlled trial will demonstrate gyy programme effective costeffective viable addition management older adults multimorbiditytrial registrationisrctn isrctn13567538 registered 18 march 2019,0.0
decreased blood cd4+ t lymphocyte helps predict cognitive impairment patients amyotrophic lateral sclerosis background als patients changed peripheral immunity unknown whether peripheral immunity related cognitive dysfunction als patientsobjectiveto explore relationship peripheral blood lymphocyte subsets cognitive status als patientsmethodsamong 81 als patients compared demographic clinical peripheral levels total t lymphocyte cd4+ t lymphocyte cd8+ t lymphocyte b lymphocyte nk cell cognitive impairment alsci without alsnci cognitive status evaluated via chinese version edinburgh cognitive behavioral screen ecas significant predictors cognitive impairment univariate logistic regression analysis examined using multivariate logistic regression analysisresults395 als patients cognitive impairment alsci group shorter education time older age symptom onset testing longer disease duration lower levels peripheral total cd4+ cd8+ t lymphocyte b lymphocyte alsnci group frequency behavioral impairment differ two groups parameters significant differences identified group comparison also significant predictors cognitive impairment univariate logistic regression analysis except level b lymphocyte older age testing education time less 9 years lower level cd4+ t lymphocyte remained significant multivariate logistic regression analysis predictive model combining three parameters area receiver operating characteristic curve value 0842 sensitivity 906 specificity 673conclusionin chinese als patients blood cd4+ t lymphocyte might help evaluate cognitive impairment along age education level,0.0
automated vivo tracking cortical oligodendrocytes front cell neurosci 2021 apr 12 15667595 doi 103389 fncel2021667595 ecollection 2021abstractoligodendrocytes exert profound influence neural circuits accelerating action potential conduction altering excitability providing metabolic support oligodendrogenesis continues adult brain essential myelin repair uncovering factors control dynamics necessary understand consequences adaptive myelination develop new strategies enhance remyelination diseases multiple sclerosis unfortunately methods exist analysis oligodendrocyte dynamics even fewer suitable vivo investigation describe development fully automated cell tracking pipeline using convolutional neural networks oligotrack provides rapid volumetric segmentation tracking thousands cells weeks vivo system reliably replicated human analysis outperformed traditional analytic approaches extracted injury repair dynamics multiple cortical depths establishing oligodendrogenesis cuprizonemediated demyelination suppressed deeper cortical layers volumetric data provided analysis revealed oligodendrocyte soma size progressively decreases generation declines prior death providing means predict cell age eventual cell death individual time points new cnnbased analysis pipeline offers rapid robust method quantitatively analyze oligodendrocyte dynamics vivo will aid understanding changes myelinating cells influence circuit function recovery injury diseasepmid33912017 pmcpmc8072161 doi103389 fncel2021667595,1.0
ilc3 central innate immune component gutbrain axis multiple sclerosis front immunol 2021 apr 12 12657622 doi 103389 fimmu2021657622 ecollection 2021abstractgut immune cells increasingly appreciated important players central nervous system cns autoimmunity animal models multiple sclerosis ms among gut immune cells innate lymphoid cell type 3 ilc3 special interest ms research represent innate cell counterpart major pathogenic cell population ms ie t helper th 17 cells importantly cells shown stimulate regulatory t cells treg counteract pathogenic th17 cells animal models autoimmune diseases besides also well known ability stabilize intestinal barrier shape immune response gut microbiota thus proper maintenance intestinal barrier establishment regulatory milieu gut performed ilc3 may prevent activation cns antigenspecific th17 cells molecular mimicry recent findings role ilc3 gutcns axis relevance ms pathogenesis will discussed paper possibilities ilc3 functional modulation benefit ms patients will addressed wellpmid33912185 pmcpmc8071931 doi103389 fimmu2021657622,0.0
informing public health response covid19 systematic review risk factors disease severity mortality background severe acute respiratory syndrome coronavirus2 sarscov2 challenged public health agencies globally order effectively target government responses critical identify individuals risk coronavirus disease19 covid19 developing severe clinical signs mortality undertook systematic review literature present current status scientific knowledge areas describe need unified global approaches moving forwards well lessons learnt future pandemicsmethodsmedline embase global health searched end april 2020 well web science search terms specific sarscov2 virus covid19 comparative studies risk factors setting population group language included titles abstracts full texts screened two reviewers extracted duplicate standardised form data extracted risk factors covid19 disease severe disease death narratively descriptively synthesisedresultsone thousand two hundred thirtyeight papers identified postdeduplication thirtythree met inclusion criteria 26 china six assessed risk contracting disease 20 risk severe disease ten risk dying age gender comorbidities commonly assessed risk factors weight evidence showed increasing age associated severe disease mortality general comorbidities mortality seven studies presented multivariable analyses power generally limited wide range definitions used disease severityconclusionsthe volume literature generated short time since appearance sarscov2 considerable many studies sought document risk factors covid19 disease disease severity mortality age risk factor based robust studies consistent body evidence mechanistic studies required understand age important risk factor start pandemics large standardised studies use multivariable analyses urgently needed populations risk can rapidly protectedregistrationthis review registered prospero crd42020177714,0.0
randomized crossover pilot study examining effect carvedilol terazosin plus enalapril urinary symptoms patients hypertension benign prostatic hyperplasia urol j 2021 apr 11 doi 1022037 ujv18i5678 online ahead printabstractpurpose present study aims assess compare effects carvedilol terazosin plus enalapril lower urinary tract symptoms luts urine flow blood pressure bp patients moderate hypertension htn benign prostatic hyperplasia bph materials methods randomized crossover trial total 40 men htn luts symptoms enrolled first group treated carvedilol second one received terazosin plus enalapril eight weeks treatment patients experienced onemonth washout period treatments changed continued eight weeks diagnose bph study international prostate symptom score ipss questionnaire used moreover prostatespecific antigen psa postvoid residual pvr urine volume maximum urinary flow rate qmax using uroflowmetry test measuredresults effect assessment results crossover trial illustrated neither carryover effects significant treatment effects primary outcomes p 005 moreover results period effect indicated significant reduction bp systolic diastolic pvr ipss yet significant raise qmaxconclusion effects carvedilol similar combination terazosin enalapril patients moderate htn bph controlling luts carvedilol used appropriative drug patients moderate htn cardiac problems luts bph studies recommended conducted investigate compare efficacy carvedilol alphablockers larger sample size longer period timepmid33840085 doi1022037 ujv18i5678,0.0
confirmed disability progression provides limited predictive information regarding future disease progression multiple sclerosis mult scler j exp transl clin 2021 apr 11 7 2 2055217321999070 doi 101177 2055217321999070 ecollection 2021 aprjunabstractbackground although confirmed disability progression cdp common outcome multiple sclerosis ms clinical trials predictive value longterm outcomes uncertainobjective investigate whether cdp month 24 predicts subsequent disability accumulation msmethods comprehensive longitudinal investigation multiple sclerosis brigham womens hospital includes participants relapsingremitting ms clinically isolated syndrome expanded disability status scale edss scores 5 n 1214 cdp assessed predictor time edss score 6 edss 6 secondary progressive ms spms using cox proportional hazards model adjusted models included additional clinical participant characteristics models compared using akaikes information criterionresults cdp directionally associated faster time edss 6 univariate analysis hr 161 95 ci 083 313 adjusting month 24 edss cdp directionally associated slower time edss 6 adjusted hr 065 032 128 models including cdp worse fit statistics using edss scores without cdp models included clinical magnetic resonance imaging measures t2 lesion volume improved fit statistics results similar time spmsconclusions cdp less predictive time subsequent events ms clinical featurespmid33953937 pmcpmc8042549 doi101177 2055217321999070,0.0
phenotypic alteration macrophages osteoarthritis systematic review abstractobjectiveosteoarthritis oa long regarded disease cartilage degeneration whereas mounting evidence implies lowgrade inflammation contributes oa among inflammatory cells involved macrophages play crucial role mediated local microenvironment exhibit different phenotypes polarization states therefore conducted systematic review uncover phenotypic alterations macrophages oa summarized potential therapeutic interventions via modulating macrophagesmethodsa systematic review multiple databases pubmed web science sciencedirect medline performed february 29 2020 included articles discussed evaluated two independent reviewers relevant information analyzed standardized welldesigned templateresultsa total 28 studies included results subcategorized two sections depending sources human tissue cellbased studies 12 studies animal experiments 16 studies overall observation indicated m1 macrophages elevated synovium circulation oa development along lower numbers m2 macrophages detailed alterations macrophages synovium circulation listed analyzed furthermore interventions oa via regulating macrophages animal models highlightedconclusionthis study emphasized importance phenotypic alterations macrophages oa development classical phenotypic subcategory m1 m2 macrophages questionable due controversial conflicting results therefore efforts needed categorize macrophages exhaustive manner use advanced technologies identify individual roles subtype macrophages oa,0.0
dynamic analysis csf1rrelated leukoencephalopathy magnetic resonance imaging case report background colonystimulating factor 1 receptor csf1r related leukoencephalopathy rare rapidly progressive leukoencephalopathy characterized cognitive motor neuropsychiatric symptoms often misdiagnosed magnetic resonance imaging mri signs followup mri csf1rrelated leukoencephalopathy help establishing diagnosis features widely known general neurologistscase presentationa 34yearold man admitted progressive weakness right limbs 8 months father sister similar clinical evolution primary neurological signs hemiplegia cognitive decline dysarthria pyramidal signs ataxia parkinsonism rapid disease progression cerebrospinal fluid analysis results normal despite receiving treatment improving cerebral metabolism relieving muscle spasm symptoms improve significantly brain mri showed lesions concentrated corpus callosum deep white matter bilateral parietooccipital lobes periventricular areas corticospinal tracts enhanced lesion gadoliniumenhanced mri scan 8month progression lesions always exhibited restricted diffusion diffuse lesions gradually increased disease progressed genetic sequencing results showed novel heterozygous missense mutation c2267 t c pl756p csf1r gene patient treated citicoline idebenone 4 days improve cerebral metabolism symptoms improve significantlyconclusionthe multiple lesions involving pyramidal tract white matter showed continuously restricted diffusion brain imaging gradually increased disease progression,0.0
fish oil replacement prevents docosahexaenoic acidderived protectin dx mitigates endstagerenaldisease atherosclerotic diabetic mice abstractdiabetic nephropathy dn remains major cause endstage renal disease esrd used highfat highsucrose hfhs fed ldlr apob100 100 mice transgenic overexpression igfii pancreatic cells lrkob100 igfii model esrd test whether dietary long chain omega3 polyunsaturated fatty acids lc3farich fish oil fo prevent esrd development evaluated potential docosahexaenoic acid dha derived proresolving lipid mediators 17hydroxydha 17hdha protectin dx pdx reverse established esrd damage hfhsfed vehicletreated lrkob100 igfii mice developed severe kidney dysfunction leading esrd revealed advanced glomerular fibrosis mesangial expansion along reduced percent survival kidney failure outcome associated cardiac dysfunction revealed reduced heart rate prolonged diastolic systolic time dietary fo prevented kidney damage lean mass loss cardiac dysfunction death 17hdha reduced podocyte foot process effacement pdx treatment alleviated kidney fibrosis mesangial expansion compared vehicle treatment pdx therapy effective preserving heart function survival rate results show dietary lc3fa intake can prevent esrd cardiac dysfunction lrkob100 igfii diabetic mice data reveals pdx can protect renal failure cardiac dysfunction offering potential new therapeutic strategy esrd,0.0
neuregulins neurodegenerative diseases front aging neurosci 2021 apr 9 13662474 doi 103389 fnagi2021662474 ecollection 2021abstractneurodegenerative diseases including alzheimers disease ad parkinsons disease pd amyotrophic lateral sclerosis als typically characterized progressive neuronal loss neurological dysfunctions nervous system affecting memory motor functions neuregulins nrgs belong epidermal growth factor egf like family extracellular ligands play important role development maintenance repair central nervous system cns peripheral nervous system pns erbb signaling pathway also regulate multiple intercellular signal transduction participate wide range biological processes differentiation migration myelination review article summarized research changes roles nrgs neurodegenerative diseases especially ad elaborated structural features nrg subtype roles nrg erbb signaling networks neurodegenerative diseases also discussed therapeutic potential nrgs symptom remission neurodegenerative diseases may offer hope advancing related treatmentpmid33897409 pmcpmc8064692 doi103389 fnagi2021662474,1.0
empathy theory mind multiple sclerosis metaanalysis front psychiatry 2021 apr 9 12628110 doi 103389 fpsyt2021628110 ecollection 2021abstractmultiple sclerosis ms immunemediated demyelinating disease central nervous system studies shown ms disrupts several social cognitive abilities including empathy theory mind tom overall tom deficits ms well documented specific tom subcomponents empathic capacity affected remains unclear metaanalysis searched pubmed web science embase inception july 2020 effect sizes calculated using hedges g randomeffects model thirtythree studies included relative healthy controls hcs patients ms moderately impaired overall empathy g 067 overall tom g 74 cognitive tom g 072 overlapping domains cognitive empathy affective tom g 079 group differences identified affective empathy g 019 compared hcs patients relapsingremitting ms rrms progressive ms impaired overall empathy overall tom cognitive tom cognitive empathy affective tom without significant rrmsprogressive ms differences impairment degree conducted first metaanalytic review investigating empathy tom functioning patterns patients ms examined overlapping distinct subcomponents constructs findings suggest differential impairment core aspects social cognitive processing patients ms may importantly inform development structured social cognitive ms interventionspmid33897490 pmcpmc8062809 doi103389 fpsyt2021628110,1.0
prediction intraperitoneal adhesions using striae gravidarum scar characteristics women undergoing repeated cesarean sections background current fact increasing rates cesarean deliveries catastrophe recurrent cesareans result intraperitoneal adhesions lead maternal morbidity delivery great efforts directed towards prediction intraperitoneal adhesions provide best care laboring women aim current study evaluate role abdominal striae cesarean scar characters prediction intraperitoneal adhesionsmethodsthis case control study conducted emergency ward obstetrics gynecology department tertiary hospital june december 2019 study carried patients admitted ward fulfilling particular inclusion exclusion criteria study included two groups group one assessed presence striae degree intraperitoneal adhesions evaluated current cesarean section group two included patients without evidence abdominal striae evaluated severity adhesions also evaluation previous scar evaluation striae done using daveys scoring system scar assessed using vancouver scar scale modified nairs scoring system used evaluate intraperitoneal adhesionsresultsthe study group included 203 women control group included 205 women significant differences demographic characters recruited patients pvalue 0001 almost variables mean davey score mild moderate severe striae 182 039 357 05 673 094 respectively pvalue 0001 higher scores parameters vancouver scale present patients severe striae 169 101 173 057 267 123 135 106 scar vascularity pigmentation pliability height respectively pvalue 0001 thick intraperitoneal adhesions noted significantly women severe striae 21 4375 pvalue 0001 daveys vancouver scores showed highly significant predictive performance prediction intraperitoneal adhesions pvalue 0001 conclusionabdominal striae cesarean scar significant predictors intraperitoneal adhesions,0.0
risk factors ankle osteoarthritis treatment critical bone defects using ilizarov technique background distraction osteogenesis using ilizarov external circular fixator applied lower limb reconstructive surgery widely increasing ankle osteoarthritis oa progression severity often associated period external fixator greater relative instability ankle joint studies quantified risk factors directly techniquemethodsthe study conducted 236 patients underwent bone transport surgery tibias using ilizarov external circular fixator 2008 2018 cumulative incidence ankle oa diagnoses patients ilizarov technique treatment calculated stratified risk factors preoperative postoperative management data significant mannwhitney u test analyzed odds ratios calculated using logistic regression describe factors associated oa diagnosis including gender age bmi location bone defect diabetes hypertension osteoporosis history metal allergy glucocorticoid intake american orthopaedic foot ankle society aofas anklehf scale scores defect size ds type bone transport bone union time external fixator time eft external fixator index efi resultsthere 199 males 37 females mean age 47 years range 2859 years 236 patients 49 additional treatment ankle oa ilizarov technique treatment bone defects average followup time 21 years range 1642 years incidence postoperative ankle oa 208 19 patients classified kl grade 3 seven patients grade 4 top five risk factors included doublelevel bone transport or379 p 0005 efi 50days cm or317 p 0015 age 45years or229 p 0032 osteoporosis or158 p 0001 bmi 25 or134 p 0001 male bmi 25 diabetes osteoporosis aofas anklehf scale scores independent risk factorsconclusionsilizarov external circular fixator safe effective method treatment critical bone defects double level bone transport efi 50days cm age 45years osteoporosis bmi 25 top five relevant risk factors ankle oa probability developing ankle oa among patients three risk factors 5070,0.0
management renal tumors pregnancy case reports background renal tumors pregnancy rare treatment requires evaluation patient fetus consensus guidelines proposed verified field successfully managed three renal tumor cases pregnancy reviewed relative literaturecase presentationin first renal cell carcinoma case diagnosed 21st week pregnancy laparoscopic retroperitoneoscopic partial nephrectomy performed 26th week pregnancy second renal cell carcinoma case diagnosed 3rd week pregnancy laparoscopic retroperitoneoscopic radical nephrectomy carried abortion third angiomyolipoma case diagnosed pregnancy received treatment performed laparoscopic retroperitoneoscopic partial nephrectomy 17th week pregnancy due rapid enlargement tumorconclusionalthough consensus guidelines management renal tumors pregnant patients proposed verified general rules kidney tumor management nonpregnant patients guidelines surgery pregnancy referred renal tumors found pregnant patients require individualized treatment regimen involving surgical timing routes techniques excision ranges decided patients surgical teams,0.0
patient decision aid based multicriteria decision analysis diseasemodifying drugs multiple sclerosis prototype development background since decision making treatment diseasemodifying drugs dmds multiple sclerosis ms preference sensitive shared decision making patient healthcare professional take place patient decision aids support shared decision making process providing information disease treatment options elicit patients preference support patients healthcare professionals discussing preferences matching treatment therefore prototype patient decision aid ms patients netherlandsbased principles multicriteria decision analysis mcda developed following recommendations international patient decision aid standards mcda chosen might reduce cognitive burden considering treatment options matching patient preferences treatment optionsresultsafter determining scope include dmds labelled relapsingremitting ms clinically isolated syndrome users informational needs assessed using focus groups n 19 patients bestworst scaling surveys patients n 185 neurologists nurses n 60 determine information dmds included patient decision aid next online format computerbased delivery patient decision aid chosen enable embedding mcda literature review conducting collect evidence effectiveness burden use dmds prototype developed next alpha testing evaluate comprehensibility usability total thirteen patients four healthcare professionals identified several issues regarding content framing methods weighting importance criteria mcda structure presentation conclusions patient decision aid ranking treatment options according patients preferences adaptations made accordingly verification rankings provided validation patient decision aid evaluation feasibility implementation assessing value supporting shared decision making addressed development patient decision aidconclusionthis paper aimed provide transparency regarding developmental process mcdabased patient decision aid treatment decisions ms challenges faced process issues identified prototype resolved much possible though issues remain development needed overcome issues beta pilot testing patients healthcare professionals point clinical decisionmaking can take place ultimately enable making conclusions value mcdabased patient decision aid ms patients healthcare professionals quality care,0.0
effect alcohol central nervous system develop neurological disorder pathophysiological lifestyle modulation can potential therapeutic options alcoholinduced neurotoxication aims neurosci 2021 apr 9 8 3 390413 doi 103934 neuroscience2021021 ecollection 2021abstractthe central nervous system cns major target adverse effects alcohol extensively promotes development significant number neurological diseases stroke brain tumor multiple sclerosis ms alzheimers disease ad amyotrophic lateral sclerosis als excessive alcohol consumption causes severe neuroimmunological changes internal organs including irreversible brain injury also reacts defense mechanism bloodbrain barrier bbb turn leads changes configuration tight junction endothelial cells white matter thickness brain neuronal injury associated malnutrition oxidative stressrelated bbb dysfunction may cause neuronal degeneration demyelination patients alcohol use disorder aud however underlying mechanism still remains unknown address question studies need performed contributing mechanisms alcohol pathological relationships neurodegeneration cause permanent neuronal damage moreover alcoholinduced molecular changes white matter conduction disturbance neurotransmission likely cause myelin defect axonal loss correlates cognitive dysfunctions aud extend current knowledge developing neuroprotective environment need explore pathophysiology ethanol etoh metabolism effect cns recent epidemiological studies experimental animal research revealed association excessive alcohol consumption neurodegeneration review supports interdisciplinary treatment protocol protect nervous system improve cognitive outcomes patients suffer alcoholrelated neurodegeneration well clarify pathological involvement alcohol causing major neurological disorderspmid34183988 pmcpmc8222771 doi103934 neuroscience2021021,1.0
quot come sent canadian onequot application uptake canadian physical activity guidelines adults multiple sclerosis united states adapt phys activ q 2021 apr 9122 doi 101123 apaq20200136 online ahead printabstractthe uptake benefits canadian physical activity guidelines adults multiple sclerosis pags validated limited understanding regarding knowledge needs preferences people multiple sclerosis ms implementing pags outside clinical research authors conducted online semistructured interviews 40 persons ms across united states seeking information awareness potential approaches increasing uptake pags identified first impressions potential approaches increasing uptake pags inductive semantic thematic analysis participants perceived pags good introduction structured exercise desired information meet pags participants believed modifying pags inclusivity applying multifaceted approach dissemination implementation may increase uptake exercise behavior physical activity research ms include analyzing effects exercise unique challenges faced persons ms putting pags practicepmid33837163 doi101123 apaq20200136,0.0
association neurogranin gene expression alzheimer#39 s disease pathology perirhinal cortex alzheimers dement n y 2021 apr 9 7 1 e12162 doi 101002 trc212162 ecollection 2021abstractintroduction synaptic damage key pathology alzheimers disease ad mechanism underlying synaptic vulnerability ad remains elusivemethods using largescale transcriptomic dataset analyzed neurogranincentered integrative gene network assessed correlation neurogranin nrgn gene expression ad pathology post mortem brains studied association nrgn expression clinical dementia rating cdr neuropathological diagnosis adresults find genes positively correlated nrgn expression ad involved synaptic transmission cation channel pathways nrgn expression correlated amyloid tau pathology perirhinal cortex post mortem brains nrgn expression associated diagnosis ad correlated cdrdiscussion transcriptional regulation gene encoding synaptic protein involved selective synaptic damage ad identifying genes associated synaptic damage pathways ad may provide targets interventionpmid33860070 pmcpmc8033412 doi101002 trc212162,0.0
frequency progression current management report 16 new cases nonfunctional pancreatic neuroendocrine tumors tuberous sclerosis complex comparison previous reports front neurol 2021 apr 9 12627672 doi 103389 fneur2021627672 ecollection 2021abstractbackground tuberous sclerosis complex tsc genetic condition causes benign tumors grow multiple organ systems nonfunctional pancreatic neuroendocrine tumors pnets rare clinical feature tsc specific guidelines outlined clinical management time purpose calculate frequency nonfunctional pnets well characterize presentation current clinical management assess impact systemic mammalian target rapamycin mtor nonfunctional pnets tsc methods retrospective chart review performed query ts alliances natural history database cincinnati childrens hospital tsc database patients nonfunctional pnet clinical data two groups summarized patients identified nonfunctional pnet compared previously reported cases tsc nonfunctional pnets results calculated frequency nonfunctional pnets 065 identified 16 individuals nine males seven females median age 180 years interquartile range 155 255 just half 563 n 9 patients provided results genetic testing six pathogenic variants tsc2 whereas three pathogenic variants tsc1 average age pnet diagnosis 150 years range 346 years almost individuals diagnosed pnet routine tsc surveillance 563 n 9 mri 125 n 2 ct 25 n 4 ultrasound 62 n 1 surgical procedure follow diagnosis involved 688 n 11 serial imaging nine sixteen individuals proceeding surgical removal pnet eight individuals history using systemic mtor inhibitors tumor growth rate slightly less individuals taking mtor inhibitor 08 mm yr iqr 23 22 without 16 mm yr iqr 099 501 p 005 conclusions nonfunctional pnets occurred younger ages tsc cohort commonly compared ages prevalence reported general population pnets patients systemic mtor inhibitors lower rates growth outcome study provides preliminary evidence supporting use mtor inhibitor therapy conjunction serial imaging medical management nonfunctional pnets alternative option invasive surgical removalpmid33897589 pmcpmc8062856 doi103389 fneur2021627672,0.0
immunomodulatory effects dopamine inflammatory diseases front immunol 2021 apr 9 12663102 doi 103389 fimmu2021663102 ecollection 2021abstractdopamine da receptor significant g proteincoupled receptor classified two families d1like d1 d5 d2like d2 d3 d4 receptor families formation homodimers heteromers receptor mosaic increasing evidence suggests immune system can affected nervous system neurotransmitters dopamine recently role da receptor inflammation widely studied mainly focusing nlrp3 inflammasome nfb pathway immune cells article provides brief review structures functions signaling pathways da receptors relationships inflammation detailed descriptions roles parkinson disease inflammatory bowel disease rheumatoid arthritis systemic lupus erythematosus multiple sclerosis article provides theoretical basis drug development targeting da receptors inflammatory diseasespmid33897712 pmcpmc8063048 doi103389 fimmu2021663102,0.0
chronic demyelination axonal degeneration multiple sclerosis pathogenesis therapeutic implications curr neurol neurosci rep 2021 apr 9 21 6 26 doi 101007 s11910021011105abstractpurpose review multiple sclerosis ms common demyelinating disease central nervous system cns inflammatory attacks ms lead demyelination axonal damage however due incomplete remyelination ms lesions remain chronically demyelinated parallel axonal degeneration cns ms patients contributing progressive disability currently approved therapies adequately restore myelin protect axons degeneration review will discuss pathophysiology axonal loss chronic demyelination ms understanding pathophysiology leading development new ms therapeuticsrecent findings ongoing research function oligodendrocytes myelin revealed importance relationship neuronal health demyelination ms leads number pathophysiologic changes contributing axonal generation among mitochondrial dysfunction persistent neuroinflammation effects reactive oxygen nitrogen species information review currently approved investigational therapies designed restore lost damaged myelin protect neuronal degeneration development therapies restore lost myelin protect neurons promising avenue investigation benefit patients mspmid33835275 doi101007 s11910021011105,1.0
gene expression profiling brain endothelial cells experimental subarachnoid haemorrhage sci rep 2021 apr 9 11 1 7818 doi 101038 s4159802187301zabstractsubarachnoid haemorrhage sah type hemorrhagic stroke associated high morbidity mortality new effective treatments needed improve outcomes pathophysiology sah complex includes early brain injury delayed cerebral ischemia characterized bloodbrain barrier bbb impairment isolated brain endothelial cells becs mice subjected sah injection blood prechiasmatic cistern used gene expression profiling identify 707 unique genes 28 transcripts 403 upregulated 304 downregulated 24 865 interrogated probe sets significantly differentially expressed mouse becs sah pathway involving prostaglandin synthesis regulation significantly upregulated sah including increased expression ptgs2 gene corresponding cox2 protein celecoxib selective cox2 inhibitor limited upregulation ptgs2 becs study defined gene expression profiling becs experimental sah provide insight bbb pathophysiology may relevant neurological diseases traumatic brain injury brain tumours ischaemic stroke multiple sclerosis neurodegenerative disorderspmid33837224 doi101038 s4159802187301z,0.0
association serum vitamin d levels frequency relapses patients multiple sclerosis cureus 2021 apr 9 13 4 e14383 doi 107759 cureus14383abstractintroduction multiple sclerosis ms immunemediated inflammatory disease central nervous system affecting myelin sheath neurons wide range symptoms among various risk factors studied can increase relapse vitamin d also potential risk factor study will determine association vitamin d status frequency relapses patients ms material methods seventyfour 74 patients confirmed diagnosis ms one 01 relapse per year minimum two years included case group seventyfour 74 participants confirmed diagnosis ms one 01 relapse per year minimum two years included control group informed consent patient blood drawn via phlebotomy sent lab vitamin d levels results mean serum vitamin d level significantly lower case group compared control group 1821 421 ng ml vs 2921 572 ng ml pvalue 00001 number participants vitamin d level less 30 ng ml significantly higher patients case group compared control group 7837 vs 500 pvalue 00003 conclusion study patients relapses per year low level serum vitamin d emerging strong evidence vitamin d plays important role pathogenesis progression disease burden autoimmune disease including mspmid33987049 pmcpmc8110290 doi107759 cureus14383,1.0
correlations among disability antiaqp4 antibody status prognosis spinal cord involved patients nmosd background neuromyelitis optica spectrum disorder nmosd rare neuroinflammatory disorder central nervous system typically involves optic nerve spinal cord specific brain regions relapse disease factors associated clinical features lesion severity important clinicians predict diseaserelated disabilitymethodswe retrospectively analyzed 22 female patients nmosd spinal cord lesions detailed clinical features onset symptoms motor disability relapse episodes serum aquaporin4 aqp4 myelin oligodendrocyte glycoprotein mog autoantibodies mri characteristics documented correlate associations nadir threemonth expanded disability status scale edss scores patients threemonth edss scores four 4 categorized good outcome group scores four 4 categorized poor outcome groupresultsin patients nmosd mean age 445 128 years mean threemonth edss score 43 19 significantly higher alllimb muscle power score found good edss group poor edss group p 001 tendency toward longer followup periods lower antiaqp4 antibody levels found good outcome group serum antiaqp4 antibodies present 86 patients nmosd mog autoantibodies found one antiaqp4 antibodynegative patient 333 patients nmosd 40 spinal cord lesions distributed middle cervical upper thoracic levelsconclusionsour findings suggest edss scores mrc scores nadir significant associations threemonth edss scores topographic distributions spinal cord lesions might relate different serum antiaqp4 antibody status however studies will needed corroborate finding,1.0
skin reactions patients multiple sclerosis receiving cladribine treatment neurol neuroimmunol neuroinflamm 2021 apr 9 8 3 e990 doi 101212 nxi0000000000000990 print 2021 mayabstractobjective report 77 patients multiple sclerosis ms developed skinrelated adverse events aes following treatment cladribinemethods evaluated prospective bicentric cladribine cohort cladribinetreated patients skin ae identifiedresults two hundred thirtynine cladribinetreated patients ms evaluated seventyseven patients 32 showed least 1 skin ae median 1 month cladribine initiation range 112 within first 3 months following last cladribine exposition hair thinning n 28 12 skin rash n 20 8 mucositis n 13 5 pruritus n 6 3 observed furthermore 35 patients 15 developed herpes virus infections time since last cladribine exposition median 83 range 10305 15 patients herpes zoster infection severe ctcae grade 3 required hospitalization delayed skin aes 3 months cladribine treatment cycle involved 1 case leukocytoclastic vasculitis 2 cases alopecia areata finally 2 patients presented total 3 isolated precancerous lesions 1 leukoplakia simplex 2 actinic keratosis 1 patient developed squamous cell carcinomaconclusion skin aes common patients ms treated cladribine risk management plans adjusted include phenomena clinicians perform thorough clinical followup suspicious cases seek early interdisciplinary support light observed delayed skin reactions emphasize necessity careful clinical surveillance cladribinetreated patients yet undescribed secondary autoimmune eventsclassification evidence study provides class iv evidence skinrelated aes frequent patients ms following cladribine realworld settingpmid33837059 doi101212 nxi0000000000000990,0.0
personcentred care osteoarthritis inflammatory arthritis scoping review peoples needs outside healthcare background arthritis regardless cause significant physical social psychological impacts patients aimed identify nonhealthcare needs perceived patients inflammatory arthritis ia osteoarthritis oa determine differmethodswe electronically searched medline psycinfo embase cinahl 19902020 systematically identify nonhealthcarerelated needs people ia oa citations screened quality appraised two reviewers data extracted single reviewerresultsthe search identified 7853 citations 31 studies included 12 oa 20 ia six areas need emerged similar group 1 assistance activities daily living especially related lack independence 2 social connectedness need social participation 3 financial security worry financial security increased costs healthseeking behaviours 4 occupational needs desire continue work financial social reasons facilitated flexibility workplace conditions environment 5 exercise leisure including limitation due pain 6 transportation limitations ability drive take public transport due mobility concerns many areas need linked eg loss employment requiring support family associated sense failure loss identity social isolationconclusionsthis review highlights pervasive impact arthritis peoples lives regardless aetiology albeit limited evidence base improved identification targeting nonhealthcare needs people arthritis likely improve personcentred care,0.0
prolonged sarscov2 illness patient receiving ocrelizumab multiple sclerosis open forum infect dis 2021 apr 8 8 7 ofab176 doi 101093 ofid ofab176 ecollection 2021 julabstractwe describe case prolonged severe acute respiratory syndrome coronavirus 2 sarscov2 infection patient receiving ocrelizumab multiple sclerosis viral rna shedding signs symptoms persisted 69 days resolution administration convalescent plasma antiviral therapy case suggests risk persistent sarscov2 infection patients treated anticd20 monoclonal antibodies supports role humoral immunity disease resolutionpmid34258310 pmcpmc8083367 doi101093 ofid ofab176,0.0
reference programme diagnosis treatment headache disorders facial pain danish headache society 3rd edition 2020 abstractheadache facial pain among common disabling costly diseases europe demands high quality health care levels within health system role danish headache society educate advocate needs patients headache facial pain therefore danish headache society launched third version guideline diagnosis organization treatment common types headaches facial pain denmark second edition published danish 2010 great success new knowledge treatments emerged timely revise guideline recommendations primary headaches facial pain largely accordance european guidelines produced european academy neurology guideline used practical tool use daily clinical practice primary care physicians neurologists common interest headache well healthcare professionals treating headache patients guideline first describes examine diagnose headache patient headache treatment organized denmark description followed sections characteristics diagnosis treatment common primary secondary headache disorders trigeminal neuralgia guideline includes many tables facilitate quick overview finally particular challenges regarding migraine female hormones well headache children addressed,0.0
idiopathic retinal arterial occlusive vasculitis setting multiple arterial occlusions j ophthalmol case rep 2021 apr 8 22101086 doi 101016 jajoc2021101086 ecollection 2021 junabstractpurpose present patient vasoocclusive retinal vasculitis summarize uncommon entity review clinical features management challenges applicable patients retinal vasculitisobservations 76yearold male presented suddenonset severe central vision loss examination vitreous hemorrhage neovascularization optic nerve peripheral segmental periphlebitis vessel sclerosis vascular sheathing retinal hemorrhages observed diagnosis active vasoocclusive retinal vasculitis made patient underwent complete infectious inflammatory neoplastic workup returned negative patient treated locally subtenons injection 40 mg triamcinolone presentation later oral prednisone threemonth followup vision improved 20 300 regressing neovascularization clearing vitreous hemorrhage right eye od conclusions considering novel associations occlusive retinal vasculitis important recognize idiopathic occlusive retinal vasculitis although uncommon can occur represents prototypical disease form imperative patients complete infectious inflammatory neoplastic workup owing possible overlap masquerade clinical signs symptomspmid33912730 pmcpmc8065184 doi101016 jajoc2021101086,0.0
gene expression profiles yap1 taz crb3 vdr familial sporadic multiple sclerosis among iranian population sci rep 2021 apr 8 11 1 7713 doi 101038 s4159802187131zabstractalterations regulatory mechanisms control process myelination nervous system may lead impaired myelination multiple sclerosis hippo pathway important mediator myelination nervous system might contribute pathophysiology ms study examined via qpcr rna expression yap1 taz crb3 key effectors hippo pathway also vdr peripheral blood 35 sporadic 37 familial ms patients also 34 healthy firstdegree relatives familial ms patients hfr 40 healthy individuals without family history disease control results showed increased expression vdr sporadic group compared groups also increased expression taz familial hfr groups compared control group familial sporadic patients displayed significantly lower level expression yap1 comparison hfr group increased expression level sporadic patients control group compared hfr group seen crb3 also assessed different clinical parameters mri characteristics patients overall findings suggest hippo pathway effectors also vdr gene may play potential role pathophysiology sporadic familial forms ms confirmation different gene expression patterns sporadic familial ms groups may obvious implications personalization therapies diseasepmid33833274 doi101038 s4159802187131z,1.0
phase iib randomized trial use 4aminopyridine guillainbarr syndrome arch rehabil res clin transl 2021 apr 8 3 2 100123 doi 101016 jarrct2021100123 ecollection 2021 junabstractobjective determine safety efficacy orally delivered 4aminopyridine 4ap persons guillainbarr syndrome gbs 6 months initial diagnosisdesign randomized doubleblind placebocontrolled crossover studysetting tertiary care clinical outpatient programparticipants nineteen participants enrolled 14 male 5 female n19 neurologic impairment secondary gbs functional loss fim motor score stable 12mo 30 50 american spinal injury motor scale twelve participants mean age 59y range 2377y completed studyinterventions 4ap doseescalation study 8 weeks period 3week washout period followed 3 months openlabel followupmain outcome measures fim motor score primary outcome measure also evaluated american spinal injury motor strength score limbs handheld dynamometer 6minute walk test medical outcomes study 12item short form center epidemiological studies depression scale positive negative affect schedule pain gbs disability scale jepsentaylor hand function test minnesota manual dexterity test minnesota rate manipulation test get go test mcgill pain inventory craig handicap assessment reporting technique participant selfevaluationresults seven participants discontinued study prematurely 3 adverse events 3 travel difficulties relocation 1 pretreatment laboratory abnormalities removing 3 participants maximum fim scores 4ap arm trended superior placebo p065 patients subjectively always tell active agent usually tingling sensations sense wellness statistically significant differences found outcome measures although strong trendsconclusions study demonstrates safety 4ap patient population gbs predominate goal study trend toward improved function treatment noted patients electing stay medication trialpmid34179759 pmcpmc8212006 doi101016 jarrct2021100123,0.0
periostin lossoffunction protects mice posttraumatic agerelated osteoarthritis background elevated levels periostin postn cartilage bone associated osteoarthritis oa however remains unknown whether postn lossoffunction can delay prevent development oa study sought better understand role postn oa development assessed functional impact postn deficiency posttraumatic agerelated oa micemethodsthe effects postn deficiency studied two murine experimental oa models using postn n 32 littermate wildtype wt mice n 36 posttraumatic oa induced destabilization medial meniscus dmm 10weekold mice n 20 agerelated oa analyzed 24monthold mice n 13 cartilage degeneration assessed histologically using oarsi scoring system synovitis evaluated measuring synovial lining cell layer cells density synovial stroma bone changes measured ct analysis serum levels postn determined elisa expression postn collagenase3 mmp13 measured immunostaining rnaseq performed chondrocytes isolated 21day old postn n 3 wt mice n 3 discover genes pathways altered postn knockoutresultspostn mice exhibited significantly reduced cartilage degeneration oarsi score relative wt mice posttraumatic oa 8 weeks maximum 237 074 vs 400 120 p 0011 summed 931 252 vs 2144 601 p 00002 spontaneous oa maximum 193 045 vs 358 116 p 0014 summed 614 157 vs 1150 302 p 0003 synovitis significantly lower postn mice wt dmm model 188 101 vs 317 063 p 0039 postn mice also showed lower trabecular bone parameters bv tv vbmd tbth tbn high tb sp models postn mice negligible levels serum postn compared wt immunofluorescent studies cartilage indicated postn mice expressed lower mmp13 levels wt mice rnaseq revealed cellcelladhesion celldifferentiation processes enriched postn mice related cellcycle dnarepair enriched wt miceconclusionspostn deficiency protects dmminduced posttraumatic agerelated spontaneous oa rnaseq findings warrant investigations better understand mechanistic role postn potential therapeutic target oa,0.0
epidemiology treatment patterns healthcare utilizations multiple sclerosis taiwan sci rep 2021 apr 8 11 1 7727 doi 101038 s41598021863473abstractrealworld data nationwide epidemiology treatment patterns multiple sclerosis ms scarce asia study aim evaluate 10years trends epidemiology treatment patterns ms taiwans national health insurance database nhird patients aged 20 years older newly diagnosed ms 2007 2016 identified crude incidences ms presented annually stratified sex age baseline characteristics treatment patterns particularly diseasemodifying drugs dmds also analyzed study included 555 ms patients mean age 369 744 female crude incidence rate ms decreased slightly 043 per 100 000 persons 2007 024 per 100 000 persons 2015 female male ratios remained mainly 2 3 approximately 80 ms patients received initial dmds interferon 1a dominant one furthermore 375 ms patients received subsequent dmds fingolimod frequently used median times diagnosis initial subsequent dmds 77 1239 days respectively nationwide study provides uptodate sophisticated estimates ms epidemiology treatment pattern realworld setting taiwanpmid33833257 doi101038 s41598021863473,0.0
phospholipase d inhibitor fipi potently blocks egfinduced calcium signaling human breast cancer cells background phosphotyrosine kinase ptk mediated phospholipase c1 plc1 signaling plays crucial role release universal second messenger calcium intracellular stores mandatory several cellular processes including cell migration however plc1 also activated ptkindependent manner phospholipase d pld derived phosphatidic acid pa higher pld expression levels pld activity also associated breast cancer cell invasion migration wondered whether might link pld plc1 investigated studymaterialsmdamb468neo egfr positive mdamb468her2 egfr her2 positive human breast cancer cells used study migratory behavior cells presence epidermal growth factor egf pld inhibitor 5fluoro2indolyldeschlorohalopemide fipi analyzed using 3d collagen matrix migration assay changes cytosolic calcium levels presence egf fipi sig1r agonists antagonists well pld1 sirna knockdown cells determined flow cytometry western blot analyses performed determine basal expression levels phosphorylation patterns egfr her2 akt mapkp42 44 plc1 sig1rresultsthe egfinduced migration mdamb468neo mdamb468her2 cells significantly impaired fipi likewise fipi also significantly abolished egfinduced calcium release cell lines however neither expression levels phosphorylation patterns egfr her2 akt mapkp42 44 plc1 markedly changed fipi knockdown pld1 expression sirna also significantly impaired egfinduced calcium release cell lines targeting sig1r interacts ip3r antagonist bd1047 also abrogated egfinduced calcium release however egfinduced calcium release also impaired cells treated sig1r agonists pre084 ppbp maleateconclusionin summary blocking pld activity specific inhibitor fipi knocking pdl1 expression sirna significantly impaired egfinduced calcium release mdamb468neo mdamb468her2 cells likely indicating connection pld activity plc1mediated calcium signaling however pld activity interferes release calcium intracellular stores remains unclear video abstract,0.0
status immunotherapy acceptance chinese patients multiple sclerosis analysis multiple sclerosis patient survival report 2018 front neurol 2021 apr 8 12651511 doi 103389 fneur2021651511 ecollection 2021abstractobjective prevalence multiple sclerosis ms china low although increasing recently owing paucity data immunotherapy acceptance chinese population conducted study analyze factors affecting acceptance immunotherapy selection diseasemodifying therapies dmts based personal clinical data patients ms methods study data obtained multiple sclerosis patient survival report 2018 first national survey patients ms china 1 212 patients ms 31 provinces treated 49 chinese hospitals 4month period may 2018 august 2018 patients asked complete online questionnaires assess understanding disease results general highly educated patients frequent relapses willing receive treatment regardless dmts immunotherapy patients understanding disease opted treated younger patient population patients severe disease course symptoms likely choose treatment moreover higher proportion women chose treated dmts immunotherapies conclusions education status patient awareness disease impact treatment acceptance chinese patients ms therefore call improving awareness ms disease social security help patients improve quality lifepmid33897605 pmcpmc8060470 doi103389 fneur2021651511,0.0
neurologic manifestations hospitalized patients covid19 mexico city plos one 2021 apr 8 16 4 e0247433 doi 101371 journalpone0247433 ecollection 2021abstractbackground coronavirus disease 2019 covid19 systemic entity frequently implies neurologic features presentation complications disease course aimed describe characteristics predictors developing inhospital neurologic manifestations large cohort hospitalized patients covid19 mexico citymethods analyzed records consecutive adult patients hospitalized march 15 june 30 2020 moderate severe covid19 confirmed reverse transcription realtime polymerase chain reaction rtrtpcr severe acute respiratory syndrome coronavirus 2 sarscov2 neurologic syndromes actively searched standardized structured questionnaire physical examination confirmed neuroimaging neurophysiology laboratory analyses applicableresults studied 1 072 cases 65 men mean age 53213 years 71 patients preexisting neurologic diseases diabetic neuropathy 17 epilepsy 15 history ischemic stroke eight migraine six multiple sclerosis one parkinson disease one 163 152 developed new neurologic complication headache 417 myalgia 385 dysgeusia 8 anosmia 7 common neurologic symptoms hospital presentation delirium 131 objective limb weakness 51 delayed recovery mental status sedation withdrawal 25 common new neurologic syndromes age headache presentation preexisting neurologic disease invasive mechanical ventilation neutrophil lymphocyte ratio 9 independent predictors new inhospital neurologic complicationsconclusions even excluding initial clinical features preexisting comorbidities new neurologic complications hospitalized patients covid19 frequent can predicted clinical information hospital admissionpmid33831042 doi101371 journalpone0247433,0.0
burden illness initiating intermittent catheterization analysis german health care claims data background intermittent catheterization ic common medical technique drain urine bladder longer possible natural means objective study evaluate standard care burden illness german individuals perform intermittent catheterization obtain recommendations improvement caremethodsa descriptive study retrospective longitudinal cohort design conducted using ingef research database german statutory health insurance claims data system study consisted individuals initial ic use 20132015resultswithin 3 years 1100 individuals initial ic identified database 19 000 german population common ic indications urologic diseases spinal cord injury multiple sclerosis spina bifida urinary tract infections uti frequent complication occurring 1 year index 61 followup year 1 60 year 2 50 resource use preindex including hospitalizations 65 length stay 128 200 days physician visits general practitioner 152 291 prescriptions antibiotics 71 healthcare costs 17 950 high comorbidities complications healthcare resource use highest 1 year index decreasing first second year indexconclusionsthe data demonstrated prior initial catheterization ic users experienced utis high healthcare utilization demonstrates potential high burden illness prior initial ic utis also decreased time suggesting ic use may positive influence findings also showed first year initial catheterization cost decreased studies needed better understand extent burden ic users compared nonic users,0.0
contribution sleep quality fatigue following stroke crosssectional study background prevalence fatigue sleep disturbances high stroke populations sleep quality can targeted interventions alleviate fatigue following stroke study aimed determine prevalence fatigue poor sleep quality quantify contribution sleep quality fatigue following stroke chronic 1 year stroke survivorsmethodsa crosssectional design adopted total 112 stroke survivors mean age standard deviation year 6418 577 608 480 years poststroke completed study participants assessed using fatigue assessment scale pittsburgh sleep quality index visual analogue scalepain fuglmeyer assessment upper lower extremities 5time sittostand test epworth sleepiness scale frenchay activities index lifespace assessment community integration measure multidimensional scale perceived social support pearson partial correlation coefficients used examine correlation fatigue variables multiple linear regression forced entry method performed quantify independent contribution sleep quality prediction fatigueresultsof 112 participants 527 reported experiencing fatigue 643 reported poor sleep quality sleep quality independently account 59 variance fatigue scores strokeconclusionsthere high prevalence fatigue poor sleep quality chinese stroke survivors sleep quality independent predictor fatigue living community survived stroke year longer,0.0
thalamic shape abnormalities patients multiple sclerosisrelated fatigue neuroreport 2021 apr 7 32 6 438442 doi 101097 wnr0000000000001616abstractthalamus plays important role pathogenesis multiple sclerosisrelated fatigue msrf however thalamus heterogeneous structure specific thalamic subregions involved condition unclear used thalamic shape analysis detailed localization thalamic abnormalities msrf using modified fatigue impact scale measured fatigue 42 patients relapsingremitting multiple sclerosis ms thalamic shape extracted t1w images using automated pipeline investigated association thalamic surface deviations severity global fatigue cognitive physical psychosocial subdomains cognitive fatigue correlated inward deformity left anteromedial thalamic surface localized shape deviation observed correlation global physical psychosocial fatigue findings indicate left anteromedial thalamic subregions implicated cognitive fatigue possibly role reward processing cognitive executive functionspmid33788816 doi101097 wnr0000000000001616,0.0
o group protective factor covid19 basque population plos one 2021 apr 7 16 4 e0249494 doi 101371 journalpone0249494 ecollection 2021abstractabo blood groups recently related covid19 infection present work performed analysis using data 412 covid19 patients 17796 blood donors gipuzkoa region northern spain results obtained confirmed relation addition showing clear importance group o protective factor covid19 disease 059 ci95 048107177 p00001 b ab risk factors abo blood groups slightly differently distributed populations therefore results replicated specific areas proper control populationpmid33826662 doi101371 journalpone0249494,0.0
diagnostic accuracy sensory motor tests diagnosis carpal tunnel syndrome systematic review background carpal tunnel syndrome cts common entrapment mononeuropathy upper extremity previous systematic review diagnostic tests cts outdated objective study compile appraise evidence accuracy sensory motor tests used diagnosis ctsmethodsmedline cinahl embase databases searched january 20 2020 studies assessing least one diagnostic accuracy property sensory motor tests cts diagnosis selected two independent reviewers diagnostic test accuracy extension prisma guidelines followed risk bias applicability concerns rated using quadas2 tool reported diagnostic accuracy property summarized study characteristics information accuracy sensory motor tests cts diagnosis extractedresultswe included sixteen clinical studies assessing thirteen different sensory motor tests sensitive test cts diagnosis semmesweinstein monofilament test 322 radial digit normal threshold sensitivity 049 096 tests highest specificity sp palmar grip strength sp 094 pinch grip strength sp 078 095 thenar atrophy sp 096 100 twopoint discrimination sp 081 098 conclusionsthe evidence inconclusive sensory motor test cts diagnosis highest diagnostic accuracy results suggest clinicians use single sensory motor test deciding cts diagnosistrial registrationprospero crd42018109031 20 december 2018,0.0
regulatory scientific ethical issues arising institutional activity one 90 italian research ethics committees background paper highlights issues one 90 italian research ethics committees recs might encounter approval phase clinical trial identify corrective preventive actions promoting efficient review process ensuring review quality publications subject italy rest europe limited encouraging constructive debate can improve recs service subject clinical trialmethodswe retrospectively reviewed cohort 822 clinical trial protocols initially reviewed rec june 2014 december 2018 data collected protocol type trial sample size use placebo number kind revisions requested rec approval time taken approval data protocol collected trained clinical research assistant using recs files electronic archivesresultsalmost 45 reviewed studies 374 822 required clarifications significant changes documentation minor changes final approvalconclusionspreventive measures needed reduce number requested corrections thus also time required approval maintaining review quality critical points proposals presented paper require harmonization updates european regulations regulatory harmonization produces better compliance rules reduces number changes required trials final approval updates include development standardized formats informed consent verification evidence favor using offlabel treatments placebo comparators using multidisciplinary staff clinical trials children adolescents improving legal definition recs assign responsibilities ensure independence providing guidance recs engage clinical research assistants internal audits,0.0
association fatigue severity maladaptive coping multiple sclerosis datadriven psychodynamic perspective front neurol 2021 apr 7 12652177 doi 103389 fneur2021652177 ecollection 2021abstractfatigue persons multiple sclerosis pwms severely disabling however underlying mechanisms remain incompletely understood recent research suggests link early childhood adversities psychological trait variables line studies paper took psychodynamic perspective msfatigue hypothesized fatigue represent manifestation maladaptive coping intense emotions schema therapeutic mode model served theoretical empirically validated framework linking psychodynamic theory empirical research methods study based data set n 571 pwms also served basis another publication data collected online schema mode inventory used quantify regulatory strategies cope emotionally stressful experiences addition depressive symptoms becks depression inventory fastscreen physical disability patient determined disease steps alexithymia toronto alexithymia scale26 adverse childhood experiences childhood trauma questionnaire selfreported fatigue fatigue scale motor cognitive functions assessed latent profile analysis revealed three distinct groups pwms based coping mode profiles 1 pwms low maladaptive coping 2 pwms avoidant submissive coping styles 3 pwms avoidant overcompensatory coping styles multivariate comparisons showed significant difference physical disability across three groups however heightened levels selfreported fatigue depression symptoms occurred pwms maladaptive coping styles path model uncovered selfreported fatigue robustly related physical disability 033 detached avoidant coping detached protector 034 specific relation maladaptive coping modes depression symptoms detached avoidant coping turn predicted childhood emotional abuse neglect results indicate childhood adversity detached avoidant coping styles may associated variability msfatigue severity pwms resort detached avoidant coping response negative emotions also tend report heightened levels fatigue although differ perceived disability pwms low levels fatigue maladaptive coping link msfatigue psychodynamic traumatic conversion model discussed implications findings therapeutic interventions require studypmid33897606 pmcpmc8058358 doi103389 fneur2021652177,0.0
crosscultural adaptation reliability validity fremantle knee awareness questionnaire italian subjects painful knee osteoarthritis background aimgrowing attention given utilising physical function measures better understand manage knee osteoarthritis oa fremantle knee awareness questionnaire frekaq selfreported measure bodyperception specific knee never validated italian patients aims study culturally adapt validate italian version frekaq frekaqi allow use italianspeaking patients painful knee oamethodsthe frekaqi developed means forwardbackward translation final review expert committee test prefinal version evaluate comprehensibility psychometric testing included internal structural validity rasch analysis construct validity assessing hypotheses frekaq correlations knee injury osteoarthritis outcome score koos pain intensity numerical rating scale pinrs pain catastrophising scale pcs hospital anxiety depression score hads pearsons correlations knowngroup validity evaluating ability frekaq scores discriminate two groups participants different clinical profiles mannwhitney u test reliability internal consistency cronbachs alpha testretest reliability intraclass correlation coefficient icc21 measurement error calculating minimum detectable change mdc resultsit took one month develop consensusbased version frekaqi questionnaire administered 102 subjects painful knee oa well accepted internal structural validity confirmed substantial unidimensionality frekaqi variance explained 533 unexplained variance first contrast showed eigenvalue 18 local dependence detected construct validity good hypotheses met correlations koos rho 038051 pinrs rho 035037 pcs rho 047 hads anxiety rho 036 depression rho 043 regarding knowngroups validity frekaq scores significantly different groups participants demonstrating high low levels pain intensity pain catastrophising anxiety depression four koos subscales p 0004 internal consistency acceptable 074 testretest reliability excellent icc 092 ci 087094 mdc95 522 scale pointsconclusionthe frekaqi unidimensional reliable valid italian patients painful knee oa use recommended clinical research purposes,0.0
virtual reality feasible intervention platform multiple sclerosis pilot protocol acute improvements affect mult scler j exp transl clin 2021 apr 7 7 2 20552173211006139 doi 101177 20552173211006139 ecollection 2021 aprjunabstractbackground people living multiple sclerosis ms experience high symptom burden interferes daily functioning virtual reality vr emerging technology range potential therapeutic applications may include ameliorating experience common ms symptomsobjective tested feasibility tolerability vr intervention preliminary effects affectmethods participants ms recruited complete pilot study eight sessions vr four weeksresults total n 16 participants ms completed study age range 2863 feasibility goals met 100 sample completing least n 4 8 intervention sessions total 119 128 93 completed sessions two n 16 participants experienced brief adverse events balance vertigo resolved headset removal otherwise treatment limiting preliminary indication overall improved affect baseline intervention end significantly improved positive affect t 15 319 p 0006 decreased negative affect t 15 225 p 0040 conclusion vr interventions feasible safe tolerable individuals living ms may improve affectpmid33889420 pmcpmc8040379 doi101177 20552173211006139,0.0
shortchain fatty acids intestinal inflammation multiple sclerosis modulation female susceptibility microbial products background multiple sclerosis ms autoimmunemediated disease central nervous system experimental data suggest role intestinal microbiota microbial products shortchain fatty acids scfas pathogenesis ms recent clinical study reported beneficial effects mediated immunomodulatory mechanisms oral administration scfa propionate ms patients based available evidence investigated whether scfas fecal inflammation marker calprotectin altered msmethods76 subjects 41 patients relapsingremitting ms 35 agematched controls investigated casecontrol study subjects underwent clinical assessment established clinical scales provided fecal samples quantitative analysis fecal scfa fecal calprotectin concentrations fecal markers compared ms patients controls analyzed association demographic well clinical parametersresultsmedian fecal calprotectin concentrations within normal range groups without groupspecific differences fecal scfa concentrations showed nonsignificant reduction ms patients compared healthy subjects female subjects showed significantly reduced scfa concentrations compared male subjectsconclusionsin cohort ms patients found evidence active intestinal inflammation yet vast majority investigated ms patients immunotherapy might affected outcome measures sexassociated difference fecal scfa concentrations might least partially explain female predominance ms largescale longitudinal studies including drugnave ms patients required determine role scfas ms distinguish diseaseimmanent effects caused therapeutic regime,0.0
vitamin d resistance possible cause autoimmune diseases hypothesis confirmed therapeutic highdose vitamin d protocol front immunol 2021 apr 7 12655739 doi 103389 fimmu2021655739 ecollection 2021abstractvitamin d3 cholecalciferol secosteroid prohormone metabolized various tissues biologically active vitamin d hormone 1 25 oh 2d3 calcitriol 1 25 oh 2d3 multiple pleiotropic effects particularly within immune system increasingly utilized within prophylaxis also within therapy various diseases context latest research revealed clinical benefits high dose vitamin d3 therapy autoimmune diseases necessity high doses vitamin d3 treatment success can explained concept acquired form vitamin d resistance etiology based one hand polymorphisms within genes affecting vitamin d system causing susceptibility towards developing low vitamin d responsiveness autoimmune diseases hand based blockade vitamin d receptor signaling eg pathogen infections paper review observational mechanistic evidence acquired vitamin d resistance hypothesis particularly focus clinical confirmation experience treating multiple sclerosis patients socalled coimbra protocol daily doses 1000 iu vitamin d3 per kg body weight can administered safely parathyroid hormone levels serum thereby provide key information finding right dose argue acquired vitamin d resistance provides plausible pathomechanism development autoimmune diseases treated using highdose vitamin d3 therapypmid33897704 pmcpmc8058406 doi103389 fimmu2021655739,0.0
magnetic resonance imaging neurological findings dogs discassociated cervical spondylomyelopathy case series background canine cervical spondylomyelopathy can separated osseous discassociated dacsm forms aim describe magnetic resonance imaging using highfield scanner neurological findings dogs dacsm investigate relationship findingsresultssixtythree dogs included 60 63 95 large breeds doberman pinschers males overrepresented 70 mean median age time diagnosis 725 72 years range 04112 years chronic signs noted 52 63 83 dogs proprioceptive ataxia common main site spinal cord compression commonly c67 c56 thirtysix 57 dogs various sites spinal cord compression dogs younger 6 years age single affected site foraminal stenosis present 51 63 dogs 81 t2weighted hyperintensity present 40 63 dogs 63 88 articular processes showed degenerative changes correlated strongly intervertebral disc degeneration ligamentum flavum hypertrophy seen 38 dogs correlation observed neurologic signs number affected sites moderate positive correlation observed severity spinal cord compression neurologic grade r 048 p 0001 conclusionsdacsm predominantly observed older male dobermans lesions located caudal cervical vertebral region also seen dogs 3 years age even younger 8 single compressive lesions common dogs younger 6 years age many dogs concomitant changes eg ligamentum flavum hypertrophy foraminal stenosis dogs ligamentum flavum hypertrophy 6 years older positive correlation observed severity spinal cord compression neurologic grade multilevel compression associated severe neurologic signs high percentage dogs articular process degenerative changes possible biomechanical genetic relationships degenerative changes articular processes ligamentum flavum intervertebral discs warrants investigation,0.0
assessment chronic allograft injury renal transplantation using diffusional kurtosis imaging background chronic allograft injury cai significant reason many grafts lost study conducted assess usefulness diffusional kurtosis imaging dki technology noninvasive assessment caimethodsbetween february 2019 october 2019 110 renal allograft recipients included analyze relevant dki parameters according estimated glomerular filtration rate egfr ml min 173 m2 level divided 3 groups group 1 egfr 60 n 10 group 2 egfr 3060 n 69 group 3 egfr 30 n 31 performed dki clinical 3t magnetic resonance imaging system measured area interest determine mean kurtosis mk mean diffusivity md apparent diffusion coefficient adc renal cortex medulla performed pearson correlation analysis determine relationship egfr dki parameters used receiver operating characteristic curve estimate predicted values dki parameters cai evaluation randomly selected five patients group 2 biopsy confirm cairesultswith increase creatinine adc md cortex medulla decrease mk cortex medulla gradually increase among three different egfr groups significant differences found cortical medullary mk p 0039 p 0001 p 0001 respectively cortical medullary adc md negatively correlated egfr r 049 044 057 057 respectively p 0001 cortical medullary mk positively correlated egfr r 042 038 p 0001 0491 set cutoff value mks cai assessment showed 87 sensitivity 100 specificity five patients randomly selected biopsy second group confirmed glomerulosclerosis tubular atrophy interstitial fibrosisconclusionthe dki technique related egfr allograft injury progresses expected become potential noninvasive method evaluating cai,0.0
deciphering multiple sclerosis progression front neurol 2021 apr 7 12608491 doi 103389 fneur2021608491 ecollection 2021abstractmultiple sclerosis ms primarily inflammatory degenerative disease central nervous system triggered unknown environmental factors patients predisposing genetic risk profiles prevention neurological disability one essential goals achieved patient ms however pathogenic mechanisms driving progressive phase disease remain unknown described pathophysiological mechanisms associated disease progression present disease onset daily practice lack clinical radiological biological markers favor early detection diseases progression different definitions disability progression used clinical trials according descriptive progression defined minimum increase expanded disability status scale edss 15 10 05 baseline level 0 1050 55 respectively nevertheless edss sensitive scale assess progression consensus regarding specific diagnostic criteria disability progression review document discusses current pathophysiological concepts associated ms progression different measurement strategies biomarkers associated disability progression available pharmacologic therapeutic approachespmid33897583 pmcpmc8058428 doi103389 fneur2021608491,0.0
data silos undermining drug development failing rare disease patients abstractdata silos proliferating research development activity explode following genetic immunological advances many clinically described disorders previously unknown etiologies latter event inspired optimism patient clinical research communities diseasespecific treatments way however fear tendency various stakeholders balkanize databases proprietary formats driven current economic academic incentives will inevitably fragment expanding knowledge base undermine current future research efforts develop muchneeded treatments proliferation proprietary databases compounded paucity meaningful outcome measures good natural history data slows ability generate scalable solutions benefit chronically underserved patient populations ways translate common diseases current research development landscape sets many projects unnecessary failure particularly rare disease sphere grave disservice highly vulnerable patients system also encourages collection redundant data uncoordinated parallel studies registries ultimately delay deny potential treatments ostensibly tractable diseases also promotes waste precious time energy resources groups national institutes health food drug administration started programs address issues however many others feel significantly discussion coordinate scale registry efforts discourse aims reduce needless complexity duplication efforts well promote precompetitive knowledge ecosystem rare disease drug development cultivates accelerates innovation,0.0
streamlined alphasynuclein rtquic assay various biospecimens parkinsons disease dementia lewy bodies abstractdefinitive diagnosis parkinsons disease pd dementia lewy bodies dlb relies postmortem finding diseaseassociated alphasynuclein synd misfolded protein aggregates central nervous system cns recent development realtime quaking induced conversion rtquic assay ultrasensitive detection synd aggregates revitalized diagnostic values clinically accessible biospecimens including cerebrospinal fluid csf peripheral tissues however current syn rtquic assay platforms vary widely thus challenging implement standardize measurements synd across wide range biospecimens different laboratories streamlined syn rtquic assay based second generation assay platform assembled entirely commercial reagents streamlined rtquic method consisted simplified protocol requiring minimal handson time allowing uniform analysis synd different types biospecimens pd dlb ultrasensitive specific rtquic detection synd aggregates achieved millionfold diluted brain homogenates nanoliters csf pd dlb cases controls comparative analysis revealed higher seeding activity synd dlb pd brain homogenates csf assay validated csf samples 214 neuropathologically confirmed cases tissue repositories 88 pd 58 dlb 68 controls yielding sensitivity 98 specificity 100 finally single rtquic assay protocol employed uniformly detect seeding activity synd pd samples across different types tissues including brain skin salivary gland colon anticipate streamlined protocol will enable interested laboratories easily rapidly implement syn rtquic assay various clinical specimens pd dlb utilization commercial products assay components will improve robustness standardization rtquic assay diagnostic applications across different sites due ultralow sample consumption ultrasensitive rtquic assay will facilitate efficient use sharing scarce resources biospecimens streamlined rtquic assay suitable track distribution synd cns peripheral tissues affected patients ongoing evaluation rtquic assay synd potential biomarker pd dlb clinically accessible biospecimens broad implications understanding disease pathogenesis improving early differential diagnosis monitoring therapeutic efficacies clinical trials,0.0
detection sarscov2 antibodies pediatric kidney transplant patients background seroprevalence sarscov2 infection studied immunocompetent children however data pediatric kidney transplant population pkt lackingmethodsusing two commercial immunoassays measured igg antibodies sarscov2 spike protein igg nucleocapsid n protein screened 72 pkt recipients attended outpatient clinic routine blood work majority patients positive serology underwent additional serology test least subsequent clinical followup patients confirmed sarscov2 infection two positive testsresultseight patients 72 screened 111 positive results sarscov2 igg antibodies serological tests tested positive 4 positive sarscov2 pcr results screening patients asymptomatic history mild symptoms tested patients persistently positive antibodies median followup time 75 days iqr 445 865 days one patient positive pcr test 75 days positive serology test 120 days post infectionconclusionthe seroprevalence sarscov2 relatively high 111 population although patients asymptomatic mildly symptomatic mounted strong humoral immune response persisted months despite triple immunosuppressants findings positive implications regarding vaccination efficacy group,0.0
neural stem cells traffic functional mitochondria via extracellular vesicles plos biol 2021 apr 7 19 4 e3001166 doi 101371 journalpbio3001166 online ahead printabstractneural stem cell nsc transplantation induces recovery animal models central nervous system cns diseases although replacement lost endogenous cells originally proposed primary healing mechanism nsc grafts now clear transplanted nscs operate via multiple mechanisms including horizontal exchange therapeutic cargoes host cells via extracellular vesicles evs evs membrane particles trafficking nucleic acids proteins metabolites metabolic enzymes lipids entire organelles however function contribution cargoes broad therapeutic effects nscs yet fully understood mitochondrial dysfunction established feature several inflammatory degenerative cns disorders potentially treatable exogenous stem cell therapeutics herein investigated hypothesis nscs release traffic functional mitochondria via evs restore mitochondrial function target cells untargeted proteomics revealed significant enrichment mitochondrial proteins spontaneously released nscs evs morphological functional analyses confirmed presence ultrastructurally intact mitochondria within evs conserved membrane potential respiration found transfer mitochondria evs mtdnadeficient l929 rho0 cells rescued mitochondrial function increased rho0 cell survival furthermore incorporation mitochondria evs inflammatory mononuclear phagocytes restored normal mitochondrial dynamics cellular metabolism reduced expression proinflammatory markers target cells transplanted animal model multiple sclerosis exogenous nscs actively transferred mitochondria mononuclear phagocytes induced significant amelioration clinical deficits data provide first evidence nscs deliver functional mitochondria target cells via evs paving way development novel cellular approaches aimed restoring mitochondrial dysfunction multiple sclerosis also degenerative neurological diseasespmid33826607 doi101371 journalpbio3001166,0.0
karyomegalic interstitial nephritis diagnosed suspected background karyomegalic interstitial nephritis kin uncommon cause chronic interstitial nephritis eventually progresses endstage renal disease overall less 50 cases reported literaturecase presentationwe describe asymptomatic 25yearold gentleman family history chronic interstitial nephritis came check status kidney functions evaluation found chronic interstitial nephritis attributed specific etiology renal biopsy confirmed diagnosis kinconclusionkin remains underdiagnosed important recognize entity familial nature wide range differential diagnoses prognostic implications high index clinical suspicion necessary perform renal biopsy remains gold standard diagnosis kin,0.0
randomized study natalizumab dosing regimens relapsingremitting multiple sclerosis backgroundrefine exploratory dose frequencyblinded prospective randomized doseranging study relapsingremitting multiple sclerosis rrms patientsobjectiveto examine efficacy safety tolerability natalizumab administered via various regimens rrms patientsmethodsclinically stable rrms patients previously treated 300 mg natalizumab intravenously 12 months randomized one six natalizumab regimens 60 weeks 300 mg administered intravenously subcutaneously every 4 weeks q4w 300 mg intravenously subcutaneously every 12 weeks q12w 150 mg intravenously subcutaneously q12w primary endpoint mean cumulative number combined unique active magnetic resonance imaging mri lesions week 60resultsin total 290 patients enrolled q12w dosing arms associated increased clinical mri disease activity closed early 395 patients q12w arm met rescue criteria 300 mg intravenous subcutaneous q4w arms mean cumulative number combined unique active mri lesions 023 002 respectively annualized relapse rates 007 008 respectively trough natalizumab serum levels 4integrin saturation comparableconclusionnatalizumab 300 mg subcutaneous q4w comparable 300 mg intravenous q4w dosing respect efficacy pharmacokinetics pharmacodynamics safety,0.0
epigenetics bloodbrain barrier disruption abstractthe vessels central nervous system cns unique barrier properties endothelial cells ecs comprise cns vessels contribute barrier via strong tight junctions specific transporters limited endocytosis combine protect brain toxins maintains brain homeostasis bloodbrain barrier bbb leakage serious secondary injury various cns disorders like stroke brain tumors neurodegenerative disorders currently drugs therapeutics available treat specifically bbb damage brain injury growing knowledge field epigenetics can enhance understanding gene level bbb great potential development novel therapeutic strategies targets repair disrupted bbb brief review summarize epigenetic mechanisms regulators protective disruptive role components bbb along promising approaches regain integrity bbb,0.0
gamermri multiple sclerosis identifies diffusionbased microstructural measures sensitive focal damage deeplearningbased analysis clinicobiological validation front neurosci 2021 apr 6 15647535 doi 103389 fnins2021647535 ecollection 2021abstractconventional magnetic resonance imaging cmri multiple sclerosis ms patients provides measures focal brain damage activity fundamental disease diagnosis prognosis evaluation response therapy however cmri insensitive damage microenvironment brain tissue heterogeneity ms lesions contrast damaged tissue can characterized mathematical models multishell diffusion imaging data measure different compartmental water diffusion work obtained 12 diffusion measures eight diffusion models applied deeplearning attentionbased convolutional neural network cnn gamermri select discriminating measures classification ms lesions perilesional tissue attention weights furthermore provided clinical biological validation chosen metricsand discriminative combinationsby correlating respective mean values ms patients corresponding expanded disability status scale edss serum level neurofilament light chain snfl measures disability neuroaxonal damage results show neurite density index neurite orientation dispersion density imaging noddi measures intraaxonal isotropic compartments microstructural bayesian approach measure intraaxonal compartment spherical mean technique noddi discriminating respective attention weights 012 012 015 013 addition combination neurite density index noddi measures intraaxonal isotropic compartments microstructural bayesian approach exhibited stronger correlation edss snfl individual measures work demonstrates proposed method might useful select microstructural measures discriminative focal tissue damage may also combined unique contrast achieve stronger correlations clinical disability neuroaxonal damagepmid33889069 pmcpmc8055933 doi103389 fnins2021647535,0.0
variants novel immunomodulatory fc receptor like 5 gene associated multiple sclerosis susceptibility polish population front neurol 2021 apr 6 12631134 doi 103389 fneur2021631134 ecollection 2021abstractfc receptors shown play role several autoimmune diseases aimed test first time whether single nucleotide variants fcrl5 gene associated multiple sclerosis ms susceptibility clinical manifestations polish population casecontrol study included 94 individuals ms 160 healthy subjects genotyped two single nucleotide variants fcrl5 gene rs2012199 rs6679793 age onset disease duration clinical condition ms subjects analyzed statistical analysis used chisquared test confirmed fishers exact test observed significant differences distribution investigated fcrl5 genotypes ms subjects healthy controls cc ct genotypes well c allele rs2012199 significantly common ms subjects genotypes aa ag allele rs6679793 noted decreased ms susceptibility associated t allele rs2012199 037 p 00002 g allele rs6679793 06 p 002 results support role fcrl5 locus ms predisposition extend evidence influence autoimmunitypmid33889124 pmcpmc8055847 doi103389 fneur2021631134,0.0
structural clinical correlates periventricular gradient neuroinflammation multiple sclerosis neurology 2021 mar 18101212 wnl0000000000011700 doi 101212 wnl0000000000011700 online ahead printabstractobjectives explore invivo innate immune cell activation function distance ventricular csf patients multiple sclerosis ms using 18f dpa714 pet investigate relationship periventricular microstructural damage evaluated magnetization transfer ratio mtr trajectories disability worseningmethods thirtyseven ms patients nineteen healthy controls underwent mri 18f dpa714 tspo dynamic pet individual maps voxels characterized innate immune cell activation dpa+ generated white matter wm divided 3mmthick concentric rings radiating ventricular surface toward cortex percentage dpa+ voxels mean mtr extracted ring twoyear trajectories disability worsening collected identify patients without recent disability worseningresults percentage dpa+ voxels higher patients compared controls periventricular wm p610e6 declined increasing distance ventricular surface steeper gradient patients compared controls p0001 gradient found periventricular lesions normalappearing wm total wm correlated gradient microstructural tissue damage measured mtr rs065 p10e3 compared clinically stable patients patients disability worsening characterized higher percentage dpa+ voxels periventricular normalappearing wm p0025 conclusions results demonstrate ms innate immune cell activation predominates periventricular regions associates microstructural damage disability worsening result diffusion proinflammatory csfderived factors surrounding tissuespmid33737372 doi101212 wnl0000000000011700,0.0
identifying multiple sclerosis subtypes using unsupervised machine learning mri data nat commun 2021 apr 6 12 1 2078 doi 101038 s41467021222652abstractmultiple sclerosis ms can divided four phenotypes based clinical evolution pathophysiological boundaries phenotypes unclear limiting treatment stratification machine learning can identify groups similar features using multidimensional data classify ms subtypes based pathological features apply unsupervised machine learning brain mri scans acquired previously published studies use training dataset 6322 ms patients define mribased subtypes independent cohort 3068 patients validation based earliest abnormalities define ms subtypes cortexled normalappearing white matterled lesionled people lesionled subtype highest risk confirmed disability progression cdp highest relapse rate people lesionled ms subtype show positive treatment response selected clinical trials findings suggest mribased subtypes predict ms disability progression response treatment may used define groups patients interventional trialspmid33824310 doi101038 s41467021222652,0.0
cd11c+cd88+cd317+ myeloid cells critical mediators persistent cns autoimmunity proc natl acad sci u s 2021 apr 6 118 14 e2014492118 doi 101073 pnas2014492118abstractnatalizumab humanized monoclonal antibody mab 4integrin reduces number dendritic cells dc cerebral perivascular spaces multiple sclerosis ms selective deletion 4integrin cd11c+ cells curtail migration central nervous system cns ameliorate experimental autoimmune encephalomyelitis eae generated cd11ccre+ itga4 fl fl c57bl 6 mice selectively delete 4integrin cd11c+ cells active immunization adoptive transfer eae models employed compared wt controls multiparameter flow cytometry utilized immunophenotype leukocyte subsets singlecell rna sequencing used profile individual cells 4integrin expression cd11c+ cells significantly reduced primary secondary lymphoid organs cd11ccre+ itga4 fl fl mice active eae delayed disease onset observed cd11ccre+ itga4 fl fl mice cd11c+cd88+ cells sequestered blood upon clinical eae onset cd11c+cd88+ cells appeared cns expressed cd317+ adoptive transfer experiments cd11ccre+ itga4 fl fl mice ameliorated clinical disease phenotype associated significantly diminished numbers cns cd11c+cd88+cd317+ cells human cerebrospinal fluid subjects neuroinflammation microglialike cells display coincident expression itgax cd11c c5ar1 cd88 bst2 cd317 mice show activated nave microglia expressed cd11c cd88 cd317 finally anticd317 treatment prior clinical eae substantially enhanced recovery micepmid33785592 doi101073 pnas2014492118,0.0
evolution neurofilament light chain multiple sclerosis front neurosci 2021 apr 6 15642384 doi 103389 fnins2021642384 ecollection 2021abstractmultiple sclerosis ms autoimmune inflammatory neurodegenerative disease central nervous system characterized demyelination axonal damage diagnosis prognosis mainly assessed clinical examination neuroimaging however sensitive biomarkers needed measure disease activity guide treatment decisions ms prompt individualized management can reduce inflammatory activity delay disease progression neurofilament light chain nfl neuronspecific cytoskeletal protein released extracellular fluid following axonal injury identified biomarker disease activity ms measurement nfl levels can capture extent neuroaxonal damage especially early stages disease growing body evidence shown nfl cerebrospinal fluid csf serum can used reliable indicators prognosis treatment response recently nfl shown facilitate individualized treatment decisions individuals ms review discuss characteristics make nfl highly informative biomarker depict available technologies used measurement discuss growing role serum csf nfl ms research clinical settings finally address current topics debate regarding use nfl clinical practice examine possible directions biomarker may take futurepmid33889068 pmcpmc8055958 doi103389 fnins2021642384,1.0
effect depressive symptomatology association vitamin d sleep background sleep disorders vitamin d deficiency highly prevalent health problems studies examined effect vitamin d concentrations objectively measured sleep high methodological quality temporal proximity previous analysis within lifeadultstudy suggested lower concentration serum vitamin d associated shorter later night sleep however conclusion underlying mechanisms drawn addressed question whether relationship explained presence depressive syndromes linked vitamin d deficiency sleep disturbancesmethodsit investigated whether association vitamin d concentrations night sleep parameters mediated moderated depressive symptomatology investigated subset n 1252 community sample lifeadultstudy sleep parameters objectively assessed using actigraphy based two sleep parameters calculated night sleep duration midsleep time serum 25 oh d concentrations measured using electrochemiluminescence immunoassay depressive symptomatology evaluated centre epidemiological studies depression scale mediation effect analyzed using hayes process macro tool spss windowsresultsthe depressive symptomatology neither significantly associated night sleep duration midsleep time associations vitamin d concentrations night sleep duration midsleep time mediation depressive symptomatology significant corresponding moderator analyses also nonsignificantconclusionthe associations vitamin d concentrations night sleep parameters sleep duration midsleep time seem neither mediated moderated depressive symptomatology,0.0
phaseiia randomized doubleblind shamcontrolled parallel group trial anodal transcranial direct current stimulation tdcs left right tempoparietal junction autism spectrum disorderstimat study protocol clinical trial background autism spectrum disorder asd characterized impaired social communication interaction stereotyped repetitive behaviour sensory interests date effective medication can improve social communication interaction asd effect sizes behaviourbased psychotherapy remain low medium range consequently clear need new treatment options asd associated altered activation connectivity patterns brain areas process social information transcranial direct current stimulation tdcs technique applies weak electrical current brain order modulate neural excitability alter connectivity combined specific cognitive tasks allows facilitate consolidate respective training effects therefore application tdcs brain areas relevant social cognition combination specific cognitive training promising treatment approach asdmethodsa phaseiia pilot randomized doubleblind shamcontrolled parallelgroup clinical study presented aims investigating 10 days 20min multichannel tdcs stimulation bilateral tempoparietal junction tpj 20 ma combination computerbased cognitive training perspective taking intention emotion understanding can improve social cognitive abilities children adolescents asd main objectives describe change parentrated social responsiveness baseline within 1 week first stimulation postintervention within 7 days last stimulation monitor safety tolerability intervention secondary objectives include evaluation change parentrated social responsiveness followup 4 weeks end intervention change asd core symptoms psychopathology social cognitive abilities neural functioning postintervention followup order explore underlying neural cognitive mechanismsdiscussionif shown positive results regarding change parentrated social cognition favourable safety tolerability intervention will confirm tdcs promising treatment asd coresymptoms may first step establishing new costefficient intervention individuals asdtrial registrationthe trial registered german clinical trials register drks drks00014732 registered 15 august 2018protocol versionthis study protocol refers protocol version 12 24 may 2019,0.0
stimulation regulatory t cells lactococcus lactis expressing enterotoxigenic e coli colonization factor antigen 1 retains salivary flow genetic model sjgrens syndrome background sjgrens syndrome sjs one common autoimmune diseases impacts millions people annually sjs results autoimmune attack exocrine salivary lacrimal glands women nine times likely affected men date vaccine therapeutic exists treat sjs patients must rely lifelong therapies alleviate symptomsmethodsoral treatment adhesin enterotoxigenic escherichia coli colonization factor antigen cfa fimbriae protects several autoimmune diseases antigen ag independent manner lactococcus lactis recently adapted express cfa fimbriae llcfa effectively suppresses inflammation induction infectious tolerance via agspecific regulatory t cells tregs produce il10 tgf test hypothesis cfa fimbriae can offset development inflammatory t cells via treg induction oral treatments llcfa performed spontaneous genetically defined model sjs c57bl 6nodaec1aec2 mice maintain salivary flowresultssixweek wk old c57bl 6nodaec1aec2 mice orally dosed llcfa treated every 3 wks control groups given l lactis vector pbs llcfa itreated mice retained salivary flow 28 wks age showed significantly reduced incidence inflammatory infiltration submandibular lacrimal glands relative pbstreated mice significant increase foxp3+ il10 tgfproducing tregs observed moreover llcfa significantly reduced expression proinflammatory cytokines il6 il17 gmcsf ifn adoptive transfer cd4+ t cells llcfa itreated ll vectortreated mice restored salivary flow diseased sjs miceconclusionthese data demonstrate oral llcfa reduce halts sjs progression studies will provide basis future testing sjs patients,0.0
cd200r1 microglial inhibitory receptor therapeutic target mptp model parkinsons disease background suggested neuroinflammation activated microglial cells play relevant role contributes development parkinsons disease pd consequently modulation microglial activation potential therapeutic target taken account act dopaminergic neurodegeneration occurring neurological disorder several soluble membraneassociated inhibitory mechanisms contribute maintaining microglial cells quiescent surveillant phenotype physiological conditions however presence activated microglial cells brain pd patients suggests mechanisms somehow overloaded focused interest one membraneassociated mechanisms cd200cd200r1 ligandreceptor pairmethodsthe acute mptp experimental mouse model pd used study temporal pattern mrna expression cd200 cd200r1 context mptpinduced dopaminergic neurodegeneration neuroinflammation dopaminergic damage assessed tyrosine hydroxylase th immunoreactivity neuroinflammation evaluated mrna expression inflammatory markers iba1 gfap immunohistochemistry effect modulation cd200cd200r1 system mptpinduced damage determined using cd200r1 agonist cd200 ko miceresultsmptp administration resulted progressive decrease thpositive fibres striatum thpositive neurons substantia nigra pars compacta accompanied transient astrogliosis microgliosis expression pro antiinflammatory markers cd200 mrna levels rapidly decreased ventral midbrain mptp treatment transient decrease cd200r1 mrna expression repeatedly observed brain area earlier later phases contrast transient increase cd200r1 expression observed striatum administration cd200r1 agonist resulted inhibition mptpinduced dopaminergic neurodegeneration microglial cells showed signs earlier activation cd200deficient miceconclusionscollectively findings provide evidence correlation cd200cd200r1 alterations glial activation neuronal loss cd200r1 stimulation reduces mptpinduced loss dopaminergic neurons cd200 deficiency results earlier microglial activation suggesting potentiation cd200r1 signalling possible approach controlling neuroinflammation neuronal death pd,0.0
contact lens dryness discomfort symptoms sometimes neuropathic basis abstractsymptoms dryness discomfort soft contact lens wearers frequently lead discontinuation wear negative influence prefitting tear dysfunctions appears likely exacerbated challenges tear homeostasis caused contact lenses corneal mechanisms symptoms contact lens wearers different dry eye disease cornea insulated lens ambient conditions well lid wiper friction blinking symptoms dryness discomfort might consequence increased lid wiper friction blinking lens front surface becomes soiled dry exhibits rapid tear break possible cases contact lens intolerance discontinuation function lid wiper neuropathy relation possibility corneal neuropathy stagnant postlens tear pool possibility increased concentrations metabolic byproducts cellular debris bacterial exotoxins might potential disturb corneal epithelial subbasal nerves contributions contact lensinduced inflammation neuropathic changes may partly depend degree inflammatory mediators concentrated stagnant postlens tear pool appear known corneal neuropathic changes develop conditions chances neuropathic involvement may greater discomfort develops significant period successful wear history comorbid pain conditions esthesiometry vivo confocal microscopy discontinued contact lens wearers may support diagnosis contact lensrelated corneal neuralgia,0.0
paradox autophagy tuberous sclerosis complex genet mol biol 2021 apr 5 44 2 e20200014 doi 101590 16784685gmb20200014 ecollection 2021abstracttuberous sclerosis complex tsc autosomal dominant genetic disorder caused germline mutations tsc1 tsc2 genes leads hyperactivation mtorc1 pathway important negative regulator autophagy leads development hamartomas multiple organs variability symptoms presents challenge development completely effective treatments tsc one option treatment mtorc1 inhibitors targeted block cell growth restore autophagy however therapeutic effect rapamycin seems efficient early stages hamartoma development effect seems associated paradoxical role autophagy tumor establishment normal conditions autophagy directly inhibited mtorc1 situations bioenergetics stress mtorc1 releases ulk1 complex initiates autophagy process way autophagy promotes survival established tumors supplying metabolic precursors nutrient deprivation paradoxically excessive autophagy associated cell death situations spite paradoxical role autophagy alternative therapeutic strategy explored tsc review compiles findings related autophagy new therapeutic strategies targeting pathway tscpmid33821877 doi101590 16784685gmb20200014,0.0
cytokine measurements add value clinical variables predicting outcomes staphylococcus aureus bacteremia background demonstrated early dysregulated cytokine response high interleukin10 tissue necrosis factor il10 tnf ratio predicted poor outcomes patients staphylococcus aureus bacteremia sab however high interpatient variability cytokine levels observed grouped cytokine measurements quartiles assessed additive value clinical variables predicting bacterial persistence 30day mortality patients sabmethodsa multicenter observational study conducted hospitalized patients sab medical charts reviewed relevant information blood samples obtained cytokine measurements elisa interferongamma ifn interleukin il1 il6 il8 il10 il17 tissue necrosis factor tnf cytokine measurements grouped quartiles significant predictors bacterial persistence 30day mortality determined multivariable logistic regression analysis area roc curve auc analysis performed predictive performance compared models without cytokine quartilesresultsamong 606 patients sab subset patients n 239 day 1 cytokine measurements clinical data collected 53 22 persistent bacteremia accounting septic shock addition either il10 auc 0708 tnf auc 0714 quartiles measured day 1 improved model performance predicting bacterial persistence patients day 4 cytokine measurements 52 patients 85 died within 30days sab onset inclusion either il10 auc 0873 tnf auc 0879 quartiles measured day 4 significant clinical predictors coronary artery disease pitt bacteremia score 4 septic shock improved model performance mortalityconclusionsil10 tnf levels falling within range upper quartiles combined clinical variables improved model performance predicting outcomes may potentially used support aggressive management biomarkerguided studies evaluate benefit adjunctive immunotherapy sab future,0.0
possible progressive multifocal leukoencephalopathy active multiple sclerosis dimethyl fumarate central role mri informing therapeutic decisions background progressive multifocal leukoencephalopathy pml can rarely occur multiple sclerosis ms patients undergoing dimethyl fumarate dmf treatment case stresses limits current diagnostic stratification risk criteria highlighting potential role magnetic resonance imaging mri advising clinical choicescase presentationa 54 years old ms male patient treated dmf 3 years clinical stability developed subacute clinical worsening severe lymphopenia mri signs suggestive coexistence pml ms activity although viral title negative dmf discontinued clinical radiological improvementconclusionsthis case highlights challenges behind pml diagnosis especially patients fulfilling risk stratification criteria might present concurrent disease activity stressing potential role mri informing therapeutic decisions,0.0
metric learning method estimating myelin content based t2weighted mri de remyelination model multiple sclerosis plos one 2021 apr 5 16 4 e0249460 doi 101371 journalpone0249460 ecollection 2021abstractmyelin plays critical role pathogenesis neurological disorders difficult characterize vivo using standard analysis methods goal develop novel analytical framework estimating myelin content using t2weighted magnetic resonance imaging mri based de remyelination model multiple sclerosis examined 18 mice lysolecithin induced demyelination spontaneous remyelination ventral white matter thoracic spinal cord cohorts 6 mice underwent 94t mri days 7 peak demyelination 14 ongoing recovery 28 near complete recovery well histological analysis myelin associated cellularity corresponding timepoints mri framework took unsupervised learning approach including tissue segmentation using gaussian markov random field gmrf myelin cellularity feature estimation based mahalanobis distance comparison also investigated 2 regressionbased supervised learning approaches one using gmrf results another using freely available generalized additive model gam results showed gmrf segmentation 732 accurate unsupervised learning method achieved correlation coefficient 067 top quartile 078 histological myelin similar 070 top quartile 078 obtained using supervised analyses area receiver operator characteristic curve unsupervised myelin feature 0883 95 ci 08740891 significantly better supervised models detecting white matter myelin compared histology collectively metric learning using standard mri may prove new alternative method estimating myelin content ultimately can improve disease monitoring ability clinical settingpmid33819278 doi101371 journalpone0249460,1.0
m6a rna methylation regulates oncogenic signaling pathways driving cell malignant transformation carcinogenesis abstractthe m6a rna methylation prevalent internal modification mammalian mrnas plays critical biological roles regulating vital cellular processes dysregulations m6a modification due aberrant expression regulatory proteins frequently observed many pathological conditions particularly cancer normal cells undergo malignant transformation via activation modulation different oncogenic signaling pathways complex mechanisms accumulating evidence showing regulation oncogenic signaling pathways epitranscriptomic level added extra layer complexity particular recent studies demonstrated many types cancers various oncogenic signaling pathways modulated m6a modification target mrnas well noncoding rna transcripts m6a modifications rna molecules control fate metabolism regulating stability translation subcellular localizations review discussed recent exciting studies oncogenic signaling pathways modulated m6a rna modification regulators cancer provided perspectives studies regulation oncogenic signaling pathways m6a modification regulators also render potential druggable targets treatment cancer,0.0
atypical antiglomerular basement membrane glomerulonephritis patient metastatic melanoma treated mitogenactivated protein kinase immune checkpoint inhibitors case report background immune checkpoint inhibitors mitogenactivated protein kinase inhibitors become standard care patients advanced melanoma bearing v600 mutations however little known nephrotoxicity date two cases antiglomerular basement membrane glomerulonephritis exposure checkpoint inhibitors documented herein report first case patient metastatic melanoma developed linear immunoglobulin g 3+ immunoglobulin 2+ kappa 2+ lambda 1+ antiglomerular basement membrane glomerulonephritis negative serology following treatment checkpoint inhibitors subsequently mitogenactivated protein kinase inhibitorscase presentationa 58yearold caucasian male referred outpatient nephrology clinic acute kidney injury proteinuria received three cycles ipilimumab nivolumab recurrent melanoma positive braf v600e mutation metastasis lungs immunotherapy discontinued setting severe adverse effects including dermatitis colitis hepatitis persistent bilateral lung metastases left pleural metastases patient initiated dabrafenib trametinib presentation clinic 6 months later presentation blood pressure 172 89 mm hg 2+ edema bilaterally creatinine level 24 mg dl previous normal baseline urinary proteintocreatinine ratio 2 g g urinalysis showed dysmorphic erythrocytes red blood cell casts serologic testing negative antineutrophilic cytoplasmic antibodies proteinase 3 antigen myeloperoxidase antiglomerular basement membrane antibody complement levels normal renal biopsy showed focal crescentic 2 15 glomeruli cellular crescents proliferative sclerosing glomerulonephritis diffuse linear staining glomerular capillary loops dominant igg 3+ iga 2+ kappa 2+ lambda 1+ minimal changes initiated oral cyclophosphamide pulse intravenous methylprednisolone followed oral prednisone 6 months stabilized renal function reinitiation immunotherapyconclusionsacute kidney injury increasingly reported adverse effect drug classes mostly affecting tubulointerstitial compartment infrequently glomerulus although biologic effect drugs immune cells entirely understood possible brafinduced podocyte injury combination direct tcellmediated glomerular injury facilitated checkpoint inhibitors led unmasking cryptic antigens loss selftolerance autoimmunity importantly show treatment corticosteroids cyclophosphamide able improve stabilize patients renal function reinitiation immunotherapy,0.0
vaccine hesitancy patients multiple sclerosis preparing sarscov2 vaccination challenge neurol neuroimmunol neuroinflamm 2021 apr 2 8 3 e991 doi 101212 nxi0000000000000991 print 2021 mayabstractobjective vaccine hesitancy complex public health issue referring concerns safety efficacy need vaccination using pneumococcal vaccination recommend anticd20treated multiple sclerosis ms patients model assessed vaccination behavior patients ms prepare upcoming sarscov2 vaccination challengemethods medical chart review retrospectively identified patients ms treated ocrelizumab university hospital bern 20182020 pneumococcal vaccination discussed patients clinical visits highlighted aftervisit summary addressed general practitioner ocrelizumab initiation part clinical standard careresults pneumococcal vaccination performed 71 121 587 patients 50 121 413 patients vaccinated patients get pneumococcal vaccination younger vaccination vs vaccination mean 95 ci 401 361441 vs 454 419488 p 0028 frequently relapsing remitting disease course vaccination vs vaccination n 43 50 860 vs 49 71 690 p 0031 furthermore patients get vaccination frequently history comorbid psychiatric disorder vaccination vs vaccination n 12 50 240 vs 7 71 98 p 0035 conclusion study demonstrated singlecenter cohort 413 patients ms get recommended pneumococcal vaccination future research focus vaccine hesitancy vulnerable cohort patients ms improve safety ms immunotherapiespmid33811158 doi101212 nxi0000000000000991,0.0
influence radiographic parameters reduction critical shoulder angle arthroscopic lateral acromioplastya mathematical model arthrosc sports med rehabil 2021 apr 2 3 3 e799e805 doi 101016 jasmr202101021 ecollection 2021 junabstractobjectives develop mathematical model preoperative planning arthroscopic lateral acromioplasty ala evaluate role radiographic parameters regards critical shoulder angle csa methods anteroposterior ap radiographs patients underwent rotator cuff surgery screened identify true ap radiographs radiographs assessed 1 native csa 2 csa simulated resection spur present 3 amount ala necessary achieve csa 34 4 csa 5mm ala 5 lateral acromion angle 6 acromion index 7 sclerosis greater tuberosityresults total 1191 radiographs screened 124 patients included native csa large 35 56 patients 45 30 patients 24 subacromial spur detected resection reduced csa median 2 spur resection alone reduced csa 34 19 patients 153 mean amount ala achieve csa 34 39 18 mm value strongly correlated csa ala r 088 p 001 linear regression model determine amount ala achieve csa 34 follows r e q u r e d l n m m 39120 + 1165 c s n t v e multiple r2 model 0777 mean reduction csa 5mm ala 38 08 75 large csas reduced csa 3034 acromion index significant independent influence model p 427 whereas lateral acromion angle independently significant predictor required ala achieve csa 34 p 019 sclerosis greater tuberosity significantly associated csa 35 greater p 003 conclusions amount ala needed reduce large csa 34 correlates csa ala can preoperatively planned use simple equationlevel evidence level iii crosssectional design epidemiology studypmid34195647 pmcpmc8220626 doi101016 jasmr202101021,0.0
abstracts 10th international conference healthcare medical students ichams plenary session abstract a1 a1 scientific analysis microrna regulation risk genes multiple sclerosis ms giovanni andrei saw ye jeune chiara desanti claire mccoycorrespondence giovanni andrei saw ye jeuneroyal college surgeons ireland dublin irelandintroductionmultiple sclerosis ms chronic inflammatory disease characterised demyelination central nervous system young adults although cause ms unknown genomewide association studies identified 233 genetic loci associated ms susceptibility aim investigate whether risk genes predicted regulated micrornas mirnas small noncoding rnas involved posttranscriptional regulation gene expressionmethods200 nonmhc major histocompatibility complex loci 33 mhcassociated loci interrogated make list msrisk genes utilised three microrna target prediction algorithms targetscan dianamicrotcds mirdb find mirnas commonly regulated gene due limitation bioinformatic tool divided ms risk genes 7 distinctive categories based functions molecular pathways dna regulation finally list overrepresented micrornas compiled intersecting common mirnas category subsequently 7 categoriesresults90 ms risk genes selected 200 nonmhc loci 11 genes 33 mhcassociated loci found mir27 mir4775 intersections 5 different categories whereas mir590 mir548 mir19 mir3148 mir340 mir153 commonest 4 different groups table compilation targeted ms risk genes promising mirnas venn diagram representing relationships successfully generateddiscussion conclusionwe successful prediction search mir27 commonly targeted multiple pathways mir27 known potentially linked immune regulation warrants investigation altered mir27 expression may regulate ms pathology conclusion shown micrornas predicted target multiple msrisk genes microrna regulation may play significant role ms susceptibilityoral session abstracts o1o4 o1 medication nocturnal dipping profile hypertensive emergencyvarahabhatla vamsi1 ingrid prkacin2 juraj jug3 martina lovri beni4correspondence varahabhatla vamsi1king george hospital visakhapatnam india 2university zagreb school medicine zagreb croatia 3university zagreb school medicine clinical hospital merkur zagreb croatia 4university zagreb school medicine university hospital center zagreb croatiaintroductionthe aim study analyze medication used patients hypertensive crisis blood pressure 180 120mmhg impact main risk factors hypertensive emergency developmentmethodsa total 233 patients 108 male 125 female 184 hypertensive urgency 53 emergency 5444 5095 women emergency department 11 months patients divided five age groups decades starting age 40 mean 6585 years total ten groups depending type hypertensive medication using acei arb bb ccb diuretics moxonidine combinations resultsby using antihypertensive monotherapy percentage hypertensive emergencies 10000 5000 4166 3333 2105 using acei + ccb + diuretic significantly decreased number emergencies 0 1847 2105 2500 3333 adding beta blocker additionally diminished risk overall 53 patients medication 2275 68 233 patients smokers 2918 6323 male 36 patients hypertensive emergency 5294 smokers biggest number nondippers found patients took arbs diuretics ccb smallest number shown patients took acei combination moxonidine 2007 2202 smokers nondippers 5467 nonsmokers odds ratio getting hypertensive emergency case patient nondipper profile 418 confidence interval 102 1889 p 005 patients taking different medication none increased chance hypertensive emergency development odds ratio 121 p significant didnt find differences nondipping profile incidence genders 7212 males 7283 females conclusioncombinations antihypertensive medication showed benefit monotherapy higher 24hour nighttime blood pressure nondipping profile significantly associated greater change developing hypertensive emergencyo2 youtube videos handsonly compressiononly cardiopulmonary resuscitation content analysisreeya gulve anuradha joshicorrespondence reeya gulvebharati vidyapeeth deemed university medical college pune indiaintroductionyoutube videos important platform sharing relevant healthcare information due wide accessibility risk disseminating misleading information ignored purpose study evaluate content accuracy handsonly cardiopulmonary resuscitation cpr videos youtube according 2015 american heart associations guidelines aha methodsthe youtube searched videos english using eight search terms related handsonly cpr first 60 videos search term included study source videos total views number days since upload likes dislikes noted videos meeting inclusion criteria viewed scored step handsonly cpr given score 0 nonexistent incorrect information 1 sufficient information total score 0 6 assigned videoresultout 480 videos 440 excluded variety reasons 40 videos selected study 25 videos uploaded health organizations health care institutes hospitals 15 videos uploaded sources mean content score videos assessed 335 mean content score 340 videos uploaded health organizations health care institutes hospitals sources 327 statistically significant difference views per day likes dislikes content score among videos based sourcediscussionthe results presented showed majority handsonly cpr videos english youtube study day compliance aha guidelines terms providing basic information creation high quality educational videos broadcasted necessary order adequately spread accurate updated knowledge handsonly cpr lay populationo3 virtual highthroughput docking study approved drugs provides multiple novel treatment options covid19victoria chan charlsea maynard daire fitzpatrick nathan gnanasekaram maryam khan anthony chubb marian brennancorrespondence victoria chanroyal college surgeons ireland dublin irelandintroductionin november 2019 covid19 became public health emergency global concern virus continues spread rapidly drug repurposing gained interest possible treatment options however current drug candidates unsuccessful thus far translating clinic lacking therapeutic efficacy patients aim aimed use computational modelling identify novel drugs repurposing covid19 patientsmethodswe used virtual highthroughput screening dock drugs entered clinical trials two viral proteins sarscov2 rna dependent dna polymerase main protease 3clpro protease vitro data collected drugs covid19 identify activity covid19 cmax toxicityresults576 clinically tested drugs drug candidates predicted interact covid19 targets 97 candidates reached phase 167 reached phase ii 132 reached phase iii 180 reached phase iv approved drugs interest 15 antivirals 20 antibiotics 4 antifungals 1 antiparasitic drugs easily repurposed interesting categories include lung medications 4 immunomodulating 4 antithrombotic antiplatelet agents 4 may positive effects disease progression presentation drugs predicted best docking scores included drugs shown kill covid19 vitro thus validating modelling studyconclusionwe utilised virtual highthroughput screening data mining identify number drug options can repurposed quickly scale either alone combination drugs drugs potential effective use current pandemico4 investigating macrophage activation response damageassociated molecular patterns multiple sclerosisdevika dahiya caitlyn loo jennifer dowling claire mccoycorrespondence devika dahiya1royal college surgeons ireland dublin irelandalthough cause multiple sclerosis ms unknown understand active macrophages release inflammatory mediators causing symptomatic damage however trigger macrophage activation unclear investigated damage associated molecular pattern highmobilitygroupbox 1 hmgb1 can trigger macrophage activation hmgb1 ubiquitous nuclear architectural protein found upregulated csf samples active plaques ms patients measured hallmarks macrophage activation greiss assay il6 tnfa il1b elisa nfkb p65 phosphorylation western blotting mir155 rtpcr raw 2647 bone marrowderived macrophages stimulated dose timedependent manner hmgb1 tolllike receptor agonist lps positive control experiments performed triplicate 4 independent times 6 24 48 hrs lps 1 mg ml induced activation markers il6 tnfa il1b timedependent manner cell lines expected greatest lps 48 hrs hmgb1 alone 5 10 50 ng ml impact activation parameters however stimulated lps hmgb1 48 hrs statistically significant synergistic effect il6 tnfa il1b production raw2647 seen investigations imply hmgb1 can synergistically enhance inflammatory response lps stimulated macrophages impact hmgb1 later time points suggests may worsen chronic inflammation may relevant ms patients increased hmgb1 suffer chronic inflammation characterisation will explore different domains hmgb1 molecule macrophage activation well mechanism enhanced macrophage activation markersposter session abstracts p1p42 p1 novel lowdose intermittent gonadotropinreleasing hormone gnrh antagonist stimulation protocol invitro fertilization ivf austin b auyeung1 anthony auyeung2correspondence austin b auyeung1royal college surgeons ireland dublin ireland centre assisted reproductive services toronto canada 2centre assisted reproductive services toronto canada procrea fertility centre vaughan canadaintroductionfollicle stimulating hormone fsh therapy used ivf can produce premature luteinizing hormone lh surges ovulation can suppressed gnrh antagonists ant standard ant dosing 025 mg daily cycle day 5 6 ovulation trigger literature reports suggesting efficacy lower daily gnrh ant doses study undertaken determine ivf protocol using intermittent lowdose ant can suppress premature lh surge ovulation without compromising treatment outcomesmethodsin retrospective chart review ivf patients stimulated recombinant human fsh starting cycle day 3 first halfdose ant 0125 mg cetrorelix administered cycle days 6 8 2 3 days apart thereafter maintain lh levels 15 10 iu l oocyte maturation ovulation triggered recombinant human chorionic gonadotropin rhcg 36 hours prior oocyte retrievalresultsmean lh levels baseline prior second third halfdoses ant just rhcg trigger 524026 783088 563066 244022 iu l respectively n50 cycles average 1458095 oocytes retrieved cycle 53 36 embryos continuing cleavage blastocyst stages respectively n67 cycles cycles completed embryo transfer 39 resulted positive pregnancy tests 32 persisting clinical pregnancies n56 cycles average age patients 35805 years one percent 1 patients required one 63 required two 33 required three 3 required four halfdoses ant n67 cycles discussionour study first report intermittent lowdose ant ivf protocol using average 239007 doses cycle serum lh premature ovulation reliably suppressed cases detrimental effects oocyte embryology clinical outcomesp2 type 1 diabetes troubleshooting guidebook era covid19jeneva smith1 manveer singh1 raymond fung2 zoe lysy2 rebecca fine2correspondence jeneva smith manveer singh1royal college surgeons ireland dublin ireland 2michael garron hospital toronto east health network toronto canadabackgroundtype 1 diabetes complex chronic disease patients must empowered educated selfmanagement order reach glycemic targets decrease distress essential improving health outcomes avoiding complications however many patients health care providers know access reliable information regarding selfmanagement aim research improve patients selfmanagement type 1 diabetes developing easily understandable guidebook provides comprehensive information various situations patients may encountermethodswe used resources including clinical guides journal articles patient resources create outline guidebook solicited feedback diabetes educators endocrinologists conducted focus group patients ensure topics relevant patient michael garron hospital type 1 diabetes support group completed survey content usefulness guidebook incorporating feedback wrote guidebook using gathered resources assessed adapted final guidebook website formatresultsover half respondents survey indicated use guidebook month every proposed topic rated helpful better least 45 people final guidebook contains 21 overall sections deal hypoglycemia attending virtual visitsdiscussionif properly utilised guidebook will serve educational patientcentered intervention tool improve peoples selfmanagement type 1 diabetes thereby reducing negative health outcomes online tool especially useful midst covid19 pandemic limited inperson access physicians future research examine use guidebook significantly improves health outcomes seek patient feedback improve websitep3 exploratory study relationship selfperceived quality life physical activity canadian cohortgerges abdelsayed1 joseph girgis1 nivin azer2correspondence gerges abdelsayed1royal college surgeons ireland dublin ireland 2regent primacy medical center winnipeg manitobaintroductionphysical activity linked reduced risk developing cardiovascular disease stroke diabetes cancer depression positive relationship physical activity happiness aim explorative study assess relationship physical activity levels selfperceived quality life selfsatisfactionmethodsthe survey conducted two medical clinics created using combined modified versions international physical activity questionnaire world health organization quality life questionnaire survey comprised two sections including overall physical activity level selfreported quality life quality life section required participants rate overall quality life health satisfaction appearance satisfaction self satisfaction ethical approval obtained valid consent obtained participants age 18 excluded data analysed stata 16 using logistic regression controlled sexresultsthe logistic regression model found positive relationship activity level quality life 231 p 018 health satisfaction 236 p 008 appearance satisfaction 178 p 024 selfsatisfaction 158 p 032 none relationships statistically significant likely due small sample sizediscussionthis research find statistically significant relationship however mean relationship exist study small sample size owing exploratory nature meaning levels certainty required statistical significance achieved likely participants added future replications study positive trends activity levels quality life satisfaction scores will become significantp4 investigation potential growth promoting effects marinederived extracellular matrix components neurons cultured vitrofatima alabandi1 adrian dervan2 fergal obrien3correspondence fatima alabandi1royal college surgeons ireland dublin ireland 2advanced materials bioengineering research centre amber rcsi tcd dublin ireland 3tissue engineering research group department anatomy regenerative medicine royal college surgeons ireland dublin irelandintroductionthe adult mammalian central nervous system cns lacks intrinsic repair capacity following injury astroglia secrete various chondroitin sulphate proteoglycan proteins cspgs including 4sulfated cspgs c4s around injury site potently inhibit axonal regrowth however another secreted variant 6sulfated cspgs c6s possesses growthpromoting properties indicating cspg family may growth inhibitory contrast mammals fish cns also contain cspgs capable regenerating axons injury throughout adult lives suggesting may contain variants promote axonal regrowth aim vitro study screen cspgs derived 5 different fish species axongrowth promoting propertiesmethodsaqueous solutions cspg diluted 5g m polyllysine control used coat sterile coverslips seeded mouse motor neurons nsc34 7 days neurons fixed stained phalloidinfitc dapi fluorescent images acquired using nikon 90i microscope analysed using neurite tracer plugin software imagejresultsnsc34 neurons extended long neurites candidate substrates exhibited similar morphology compared control quantification mean neurite length revealed neurons grown cspgs lowest c4s c6s ratio longest neurite outgrowth groups higher c4s c6s concentrations showed lowest mean neurite outgrowthdiscussionthese results suggest neurons capable extending neurites grown marine cspgs also indicate c6s conducive stronger neurite outgrowth also marine cspgs higher c6s concentration ratios capable negating growth inhibitory effects c4s fish cspgs containing lowest c4s c6s concentration ratios properties engineered onto scaffolds bridge cns lesions help support direct axonal regrowthp5 assessing postoperative anxiety depression patients thyroid pathology amidst covid19vladimir osadchyi1 william el masri2 bradley hubbard2 antoine eskander2 albino chiodo2correspondence vladimir osadchyi1royal college surgeons ireland dublin ireland 2michael garron hospital toronto east health network toronto canadaintroductiondue unprecedented nature covid19 pandemic elective surgery around canada come screeching halt caused surgery wait lists greatly increase size increased wait times can lead negative psychological impacts patients experience uncertainty stress preoperative postoperative time periodmethodspatients placed michael garron hospital mgh thyroid surgery wait list telephone interviewed evaluated using hospital anxiety depression scale hads hads scores analysed assess psychological morbidity patients perspective elective surgery postponement obtained via descriptive surveyresultsa 36 response rate achieved 3week time period 16 patients completing hads tool descriptive survey mean hads anxiety score 786 mean hads depression score 707 fail qualify abnormal levels 938 15 16 participants indicated experienced anxiety prior thyroid surgery 625 10 16 participants indicated increased communication healthcare provider surgery reassure health pandemic 5625 9 16 participants indicated increased information regarding surgery prior operation reassure regarding health pandemicdiscussionpatients found experience postoperative anxiety depression according hads tool 938 patients indicated experienced anxiety prior operation patients indicated increased communication healthcare professionals receiving information regarding surgery can help reassure health can guide hospital administrations actions decision plans event future elective surgery postponements another pandemic second wave covid19p6 association electronic cigarette use asthma symptoms among adolescents systematic reviewabdulaziz alghanam1 ali ziyab2correspondence abdulaziz alghanam1royal college surgeons ireland dublin ireland 2health sciences center kuwait university kuwait city kuwaitintroductionelectronic cigarettes ecigarettes gained substantial popularity among adolescents recent years potential health effects ecigarette use unclearobjectivethe aim study systematically review observational studies investigated associations ecigarette use asthma symptoms among adolescentsmethodsa literature search medline database pubmed search engine conducted relevant observational studies total 603 articles identified screened nine studies met inclusion criteria included reviewresultsmost reviewed articles showed positive associations ecigarette use asthma symptoms adolescents odds ratio association current ecigarette use asthma wheeze 112 95 ci 101126 148 95 ci 124178 134 95 ci 115157 178 95 ci 115276 186 95 ci 128271 236 95 ci 189294 six nine studiesconclusionour review current literature indicates ecigarette use positively associated asthma symptoms based results provided crosssectional studies hence longitudinal studies needed corroborate observed associations public health strategies needed raise awareness among adolescents potential harm ecigarette use restrictions placed ecigarette sales marketing minorsp7 bacteriophagesbased preparations efficacy evaluation complex supporting therapy oncological patients receiving egfr inhibitorselina abdeeva1 ekaterina orlova1correspondence elina abdeeva1im sechenov first moscow state medical university sechenov university moscow russiaintroductionaccording modern data incidence dermatological toxicity dt background treatment various cancers inhibitors tyrosine kinase receptors epidermal growth factor egfr epidermal growth factor receptor reaches 9095 common methods correcting acnelike manifestations dt prescription systemic antibiotic therapy extremely undesirable patients metastatic liver damage aim study development alternative methods prevention treatment acnelike manifestations dt antiegfr therapy based study skin microbiota compositionmethodsthe composition skin microbiota evaluated sowing contents seedings standardized environment time inclusion two weeks beginning therapy study included 24 patients standard therapy scheme sts 20 patients phagoderm therapy scheme stsp statistical data processing carried using pasw statistics 18 level reliability defined 005 comparisonsresultsin groups localization voids face upper torso 85 83 respectively comparing microbiota qualitative composition significant difference flora composition detected groups dominated staphylococcus aureus escherichia coli comparative evaluation antibacterial therapy effectiveness 5th day showed 70 regression spills sts group 76 patients 80 stsp group 33 n8 sts group systemic antibiotics cancelled due increase spgt ast 152 timesdiscussionwe assume inclusion bacteriophagebased preparations maintenance therapy scheme effective can used monotherapy light severity manifestations complex therapy intermediate severe skin reactionsp8 breast cancer features nigerian ukrainian womenshekinah obinna jessica otomara vladimir porfirievich shevchenkocorrespondence shekinah obinnasumy state university sumy ukraineintroductionbreast cancer bc common malignancy women races globally number studies suggested differences breast cancer among women europe africa europe incidence bc higher africa african women tend die studies features bc among nigerian ukrainian women conductedaimto study difference bc white ukrainian black nigerian womenmaterials methodsstatistical date hospital based studies nigeria national cancer registry ukraineresultsthe incidence bc nigeria 245 per 100 000 population significantly lower ukraine714 sumy region 770 mean age presentation bc varies nigeria ukraine 48 years africa twothird women premenopausal delayed diagnostic bc nigeria related lack acceptance orthodox treatment low quality medical care local beliefs ignorance disease contrast ukraine system cancer care population developed regular screening available women certain ages increases probability detecting bc early stage result women nigeria receive palliative care bc advanced inoperableconclusionthe incidence bc low nigeria compared incidence ukraine particular sumy region may due illegality abortion high parity prolonged breast feeding nigerian women bc tends present earlier age diagnosed advanced stages results treatment unsatisfactoryp9 brewing caregiver burden crosssectional study caregiver burden alcohol use disordervishnu unnithan1 kranti kadam2correspondence vishnu unnithan1seth gs medical college kem hospital mumbai india 2department psychiatry seth gs medical college kem hospital mumbai indiaintroductionalcohol use disorder growing problem families patients bear burden caring feeling responsible relapse primary caregivers increased risk stressful life events psychiatric disorders gap literature regarding sociodemographic variables caregiver burden relation variables alcohol use disorderaims objectivesthe study assessed sociodemographic profile primary caregivers patients diagnosed alcohol use disorder per dsm v severity caregiver burden association correlations various variables sociodemographic factors alcohol usage caregiver burden also examinedmethodscrosssectional observational study carried deaddiction centre attached tertiary hospital using cochrans formula purposive sampling technique primary caregivers 80 patients recruited two months information collected using structured questionnaire caregiver burden scale statistical analysis pearsons correlation done using graphpad prismresultsthere 7875 prevalence moderate severe caregiver burden among primary caregivers positive correlation caregiver burden quantity alcohol consumed monthly alcohol expenditure years marriage association caregiver burden various sociodemographic variables found statistically significantconclusionalcohol use disorder can affect people socioeconomic classes irrespective education employment status addressing quantity expenditure alcohol consumption focus caregiver psychoeducation will significant implications rehabilitation patients alcohol use disorder motivation provided caregivers strong determinant outcome rehabilitation process caregiver support groups can provide missing spark spurs patients recoveryp10 can diagnose thoracic outlet syndrome faster neurophysiological diagnosticsagata kaczmarek anna kalek juliusz hubercorrespondence agata kaczmarekdepartment pathophysiology locomotor organs poznan university medical sciences poznan polandintroductionthoracic outlet syndrome tos group conditions characterized compression nerves arteries veins lower neck upper chest area average 65 physicians different specialities need 43 years develop tos diagnosis work like find way improve diagnostic processmethodssixteen healthy subjects 16 patients age 18 36 took part study patients clinically confirmed tos qualified outpatient clinic groups performed neurophysiological studies test raised hands von freys filaments electromyography emg electroneurography eng motor evoked potentials mep resultssensory perception studies revealed changes innervation ulnar median nerve patients group also observed abnormalities amplitudes emg recordings eng findings showed axonal type nerve injury meps recordings novum study revealed loss efferent impulses transmission along motors pathways cervical level upper extremities effectors efferent block typediscussiondetection tos symptoms neurophysiological tests 50 patients indicates usefulness complementary noninvasive diagnostics especially meps seem fast specific test evaluating tos symptoms regarding changes motor impulses transmissionp11 characterizing tumour immune microenvironment early breast canceralyssa francis1 2 luke mccaffrey1correspondence alyssa francis1rosalind morris goodman cancer research centre division experimental medicine department oncology mcgill university montreal canada2royal college surgeons ireland dublin irelandintroductionductal carcinoma situ dcis neoplastic proliferation epithelial cells confined luminal compartment mammary ducts precedes invasive ductal carcinoma idc formation 2050 dcis progresses idc however remains unclear determines likelihood progression hypothesized interactions early tumour cells immune system leads changes composition activation state tumour immune microenvironment become suppressed thereby contributing ability dcis progress idcmethodsusing panel epithelial immune signalling markers characterized tumour microenvironment coexisting dcis idc imaging mass cytometry imc across multiple patient samples controlling interindividual heterogeneity singlecell information extracted utilized categorize cells reconstruct spatial organization maps immune phenotype composition cellcell interactions tumour infiltrating lymphocytes tils evaluated nearest neighbour analysis performed statistical analysis done using anova shannons diversity index kullbackleibler divergenceresultsalthough significant interpatient heterogeneity observed respect immune cell composition overall activation state immune microenvironment indicated suppressed phenotype acquired progression idc evidenced significant increase tils well decrease proportion cd8 t cells cd4 t cells observed idc tumours comparison dcis tumours also significant increase tumour proliferation marker ki67 progression idc increase tregcd8 t cell tregmacrophage ratios also observed pointing towards suppressed microenvironment conducive tumour outgrowthconclusionthese results support hypothesis immune microenvironment acquires suppressed phenotype dcis progression can serve help guide future research investigating potential prognostic criteria dcis patientsp12 cochlear implantation children asymmetric hearing lossurvashi naraine1 cristina simoesfranklin1 2 laura viani1 2 christine sheehan2 olivia ferguson2correspondence urvashi naraine1school medicine royal college surgeons ireland dublin ireland 2national hearing implant research centre beaumont hospital dublin irelandintroductioncochlear implantation surgical procedure used treat bilateral profound sensorineural hearing loss population 99 unilateral cochlear implanted paediatric patients study aimed quantify initial level asymmetric hearing loss preimplantation also functional benefits cochlear implantation dependent many factors device usage compliance environment preimplant speech language abilities variables also considered determine benefits cochlear implantation cohort patientsmethodsthis audit reviewed clinical charts device parameters outcomes patient information obtained via beaumont hospital national hearing implant research centres records data childs preoperative auditory brainstem response abr audiogram ears classified children according hearing loss asymmetry cochlear implants device related details analysed speech perception intelligibility improvements noted see functional benefits cochlear implantation done using category auditory performance cap speech intelligibility rating sir scoresresultspatients categorized 1 3 groups based hearing loss asymmetry ranging least severe done using variables decibel difference implanted nonimplanted ear hearing loss ratio decibel differences groups 1 3 10 10299 30 respectively ratio hearing loss 09 0809 08 respectively additionally implantation device related information showed remarkable differences among groups three groups experienced improvement postimplantation cap sir scoresdiscussionupon obtaining scale quantify patients initial degree hearing loss asymmetry study confirmed functional benefits cochlear implantation three groups children regards hearing speech language performancep13 comparative study various methods fetal weight estimation term pregnancyaashvi patel1 shivani valia2correspondence aashvi patel1gcs medical college ahmedabad gujarat india 2sumandeep vidyapeeth university piparia waghodia vadodara gujarat indiaintroductionaccurate estimation fetal weight helps care newborn important parameter perinatal morbidity mortalitymethodsstudy design prospective noninterventional comparative study selection criteria inclusion criteria patients singleton pregnancies cephalic presentation came term labour pains induction labour elective full term lscs recent ultrasonography within 1 week prior delivery exclusion criteria abnormal pregnancy estimated fetal weight calculated clinical methods dares johnsons method sonographically hadlocks formula estimated weights compared actual birth weightresults2kg methods used statistically significant differences 2025 35kg hadlocks formula found better 2530kg dares method correlated well actual fetal weight 3035kg johnsons formula correlated welldiscussion74 cases belonged group 2535 kg dares method surpassed usg overall usg accurate amongst three methods clinical methods compared dares method better johnsons method 60 cases group 253 kg dares method showed least average error detecting fetal weight estimated fetal weight well correlated birth weight 15 error 93 cases dares method usg johnsons method true 76 cases study conducted bj0110005 kle university 95 cases dares formula usg correlated well actual birth weight error 15 studies indicate johnsons formula lags behind estimating fetal weight usg found accurate method studies available replaced dares method mean weight difference two methods statistically significantp14 comparison firsttime repeated cesarean section placentasloreta miluna beatrise gustsonecorrespondence loreta milunariga stradins university school medicine riga latviaintroductionwhat exactly can get pathological interference placental samples change gynecological ward research target determine differences histopathology firsttime repeated cesarean section placentas delivered women 3rd trimester compare themmethodsthis retrospective study included placental samples 100 women singleton gestation delivered 3rd trimester differences placental samples placental weight inflammatory process signs vascular malperfusion 80 firsttime cesarean section pregnancies 20 samples repeated sc pregnancies analysedresults65 n52 firsttime sc placentas 30 n6 repeated sc placentas maternal inflammatory response 375 n3 firsttime sc placentas none repeated sc placentas fetal inflammatory response 43 n34 firsttime sc placentas 25 n5 repeated sc placentas decreased placental weight 625 n5 placentas firsttime sc 5 n1 sc scar placental sample hemorrhage 375 n30 firsttime sc placentas 25 n5 repeated sc placentas increased syncytial nodule index level 45 n36 placentas firsttime sc 25 n5 sc scar placentas fetal retardationdiscussionsigns inflammatory process uteroplacental blood malperfusion ubm decreased placental weight multiple placental infarctions increased syncytial nodule index level common firsttime sc pregnancy although may seem repeated cesarean sections much dangerous health mother fetus one hand indicate repeated caesarean section increase complication order evaluate additionally analyze possible confounders future eg hypertension likely commonp15 cooverexpression tumour necrosis factor alpha tnfa junctional adhesion moleculea jama alpha v beta 3 integrin rhoa cd9 associated worse prognosis breast cancer patientsfaizah abubakar sani ann hopkinscorrespondence faizah abubakar saniroyal college surgeons dublin irelandintroductionjunctional adhesion moleculea jama belongs immunoglobulin superfamily proteins expressed epithelial cells endothelial cells neutrophils platelets localising intercellular tight junctions epithelial endothelial cells jama regulates adhesion neutrophil extravasation across endothelial cells jama known migrate cell surface making endothelial cells less polar aiding extravasation migration jama aided tnfa expression rhoa alpha v beta 3 integrins cd9 since jama overexpression linked poor prognosis breast cancer patients aim study determine genes associated jama overexpression extravasation also linked breast cancermethodsan online tool https kmplotcom used test correlations concurrent high mrna levels tnfa rhoa jama cd9 alpha v beta 3 integrin prognosis cohort breast cancer patientsresultspatients pt cohorts systemically treated endocrine therapy chemotherapy concurrently expressed high mrna levels jama tnfa rhoa cd9 alpha v beta 3 integrin significantly poorer relapsefree survival rfs median survival 18516 months 1975pt compared lower levels 21666 months 1976pt n3951 p00059 subdivision patient cohorts according estrogen receptor er expression status revealed fact patients er+ better outcomes coexpressed lower levels genes median survival 6871 months 1541pt er+ compared median survival 5496 months 1541pt n3082 p0033 discussionusing publiclyavailable gene expression data kaplan meier plotter able show concurrent overexpression genes associated worse outcomes breast cancer patients overall er+ patients correlations visible non er+ patients due lower number patientsp16 correlation physical activity levels depression anxiety greek young adults crosssectional studysmaragda skalidou1 emmanouil skalidis1 andreas anestis1 2 nikolaos papadakis1correspondence smaragda skalidou1laboratory hygiene socialpreventive medicine medical statistics department medicine school health sciences aristotle university thessaloniki thessaloniki greece 2division science technology american college thessaloniki thessaloniki greeceintroductiondepression anxiety disorders among underestimated threats public health especially health adolescents young adults although physical activity used medical practice treating diseases number studies investigating correlation exercise mental illnesses rather small study aimed investigate association physical activity levels depression anxiety greek young adultsmethodsa crosssectional study conducted 268 adults 91 males aged 18 26 years data obtained via onlineadministered questionnaires becks depression inventory bdi used assess participants depression status hamiltons anxiety rating scale hama used assess anxiety status chisquare test performed pearsons correlation coefficient estimated evaluating association categorical continuous ordinal variables respectively students ttest anova applied comparisons groupsresultscronbachs coefficient 0 755 indicated acceptable level internal consistency participants physical activities per week least 1020 minutes exhibited significantly lower levels depression anxiety p0 002 bdi scores p0 001 hama score interestingly although frequency duration exercise show significant correlation depression anxiety status significant correlation latter participants perception overall significance exercise identified pearsons r 0 214 bdi scores p0 001 0 190 hama score p0 002 discussionpracticing physical activities seems correlated lower depression anxiety scores study population investigation will allow additional modifiable eg lifestyle non modifiable eg gender age factors affecting association revealedp17 developing virtual communitybased deprescribing programmargarita rashev1 meghan abrahamson2 tarek dahche2 justin lin2 andrew liu2 john abrahamson3correspondence margarita rashev1royal college surgeons ireland dublin ireland 2michael garron hospital toronto east health network toronto canada 3university toronto faculty medicine michael garron hospital toronto canadaintroductioninappropriate use psychotropic medications associated higher risk adverse drug events ade evidencebased guidelines recommend gradual tapering monitoring mitigate withdrawal symptoms shortterm inpatient stays amenable tapering medications will therefore use virtual care technologies expand scope deprescribing michael garron hospital mgh toronto canada design implement hospitalbased deprescribing program patients will monitored ensuring safety process deprescribing benzodiazepines antipsychotics antidepressantsmethodspatients admitted mgh taking psychotropic medications identified using electronic health record consult physician pharmacist dyad patients substitute decision makers involved shared decisionmaking process consistent goals care patients eligible amenable will provide informed verbal consent followup via virtual care mediums patients will monitored course tapering schedule measured outcomes will include proportion patients qualify deprescribing consent virtual followup can successfully utilize technology will measure rate complete cessation dose reduction patient primary care physician community pharmacist satisfaction deprescribing balancing measures include patient barriers virtual followup ade rehospitalization ratesresultswe designed exhaustive protocol program review mgh deprescribing team members also developed patient materials including recruitment postconsultation drugspecific deprescribing informationdiscussioninappropriate use psychotropics prevalent older canadians older adults worldwide program will demonstrate utility virtual technologies deprescribing initiatives east toronto community beyondp18 development antisense oligonucleotide therapy fibrodysplasia ossificans progressivamaria mahfouz1 rika maruyama2 toshifumi yokota2correspondence maria mahfouz1school medicine faculty medicine health sciences royal college surgeons ireland dublin ireland 2department medical genetics faculty medicine dentistry university alberta edmonton alberta canadafibrodysplasia ossificans progressiva fop autosomal dominant disorder characterized progressive heterotopic ossifications ho bone forms skeletal muscle soft tissues following trauma ho induced inflammation cumulative thus patients immobile 20s fop caused mutation r206h activin receptor type acvr1 gene leading hyperactive receptor induces ho outside skeletal system currently proven treatments fop however reduction acvr1 gene expression promising therapeutic target can established using antisense oligonucleotide aso treatment short deoxynucleotide strand designed bind target mrna sequence induce mrna degradation via ribonuclease h1 furthermore central portion deoxynucleotide monomers can chimeric origin named gapmer allows allelespecific design four aso treatments using 2 methoxyethyl 2moe gapmers developed fop acvr1 mutation preferential knockdown fop allele mrna thus reducing expression mutated acvr1 receptor protein project allelespecific knockdown effect fop acvr1 mrna tested vitro using human embryonic kidney derived clonal cells hek293t cells transfected either wild type fop acvr1 dna plasmids treated either nonallelespecific mock 2moe gapmer used control one four allelespecific 2moe gapmers protein extracted transfected cells measured using western blotting western blot results showed efficient allelespecific knockdown fop acvr1 allele compared wild type allele successful preferential knockdown fop acvr1 allele paves way vivo testing ultimately new treatment agent fop patients can eventually halt progression diseasep19 efficacy safety esketamine treatment treatmentresistant depression systematic review metaanalysiskevin fernando1 aruni irfannadhira1 yehezkiel george1correspondence kevin fernando1universitas indonesia salemba indonesiaintroductiontreatmentresistant depression trd refers inadequate response taking least two antidepressant drugs esketamine enantiomer ketamine high affinity nmda nowadays esketamine widely used trd therapy oral intravenous intranasal drug however review efficacy safety esketamine trd treatment therefore conducted systematic review evaluate efficacy safety esketamine trd patientsmethodsliterature search performed databases pubmed sciencedirect cochranelibrary wiley scopus clinicalkey using treatmentresistant depression esketamine efficacy safety keyword inception october 2020 risk bias assessed cochrane rob2 primary outcome change baseline montgomeryasberg depression rating scale madrs total point end treatment period secondary outcome madrs response rate remission treatmentemergent adverse events teae metaanalysis conducted using quantitative dataresultssix highquality studies rct total 474 patients included esketamine significantly effective placebo reducing endpoint madrs md611 95ci 295 926 p00001 higher odds ratios rate response or194 95ci 107 350 p003 however remission rate esketamine placebo ketamine showed insignificant difference or169 95ci 097 296 p007 patient undergoing esketamine therapy associated several teae statistical significant difference compared placebo ketamine vertigo or938 95ci 446 1973 p00001 dissociation or905 95ci 470 1741 p00001 increased blood pressure or271 95ci 139 528 p0003 discussionin conclusion recommend esketamine adjuvant therapy treatmentresistant depression considerably effective however several adverse events vertigo dissociation increased blood pressure must taken consideration variation dose administration becomes limitation studyp20 epigenetic effects gemcitabine oxaliplatin cetuximabolga usalka1 2 varvara maksimova1 guzel sagitova2 julia makus1 3 anastasia patsyurkevich1 valeria popova4 mariana yakubovskaya1 kirill kirsanov1 3correspondence olga usalka1nn blokhin national medical research center oncology moscow russia 2im sechenov first moscow state medical university sechenov university moscow russia 3rudn university moscow russia 4moscow polytechnic university moscow russiaintroductiondna methylation histone modifications play key role epigenetic regulation gene expression aberrant changes levels chromatin modifications affect processes proliferation survival adhesion migration etc previously shown cetuximab oxaliplatin gemcitabine activate expression epigenetically repressed gfp gene hela ti test system aim study investigate effect drugs integral dna methylation level histone methylation activity histone acetyltransferases hat methodsthe level integral dna methylation analyzed restriction analysis genomic dna endonucleases hpaii sensitive unmethylated ccgg sequences mspi sensitive methylated unmethylated sites methylsensitive elisa analysis histone methylation levels performed western blotting using antibodies h3k27me3 h4k20me3 modifications activity hat family enzymes analyzed using hat activity assay kitresultswe showed treatment cells cetuximab gemcitabine affect total cytosine methylation oxaliplatin treatment decrease fraction dna cleaved methylsensitive endonuclease 31 shown densitometry analysis dna electrophoresis elisa revealed decrease cytosine methylation 18 indicates small ability oxaliplatin demethylate dna increase enzyme activity hat 20 oxaliplatin treatment changes levels histone modifications h3k27me3 h4k20me3 observed analyzed drug treatmentdiscussionconsidering oxaliplatin showed demethylating activity well tendency increase activity histone acetyltransferases can assumed drug able activate epigenetically repressed genes considered combined chemotherapy protocols developed acknowledgements work supported russian science foundation grant 187500115 p21 extent palliative care need among cancer patients undergoing chemotherapy cross sectional studysai prasad1 jangala sai vihar1 snehal bathe1 adithya mohan1 amlina priyadarshini1 lahari boddu1 rhea singh1 daanish singh1 yashaswi sinha1 vedant jha1 aishwarya aiyer1 jaiprakash gurav1 arshiya duhan1 aravind chennath1 tilak tvsvgk2correspondence sai prasad1armed forces medical college pune india 2department internal medicine armed forces medical college pune indiaintroductionpalliative care interdisciplinary approach aimed optimising quality life mitigating suffering identifying patients may benefit palliative approach recognised challenge especially india associated mainly end life care therefore assessment extent palliative care need hospital setting crucial appropriately match services define priorities caremethodsa cross sectional study conducted among cancer patients undergoing chemotherapy without adjunctive palliative care tertiary care center western maharashtra february 2020 due consent participants screened palliative care need according gold standards framework gsf prognostic indicator criteria participants also completed sheffield profile assessment referral care sparc needs assessment tool measures unmet needs across 7 domains scale 03 data entered ms excel analysed using spss version 230resultsout 127 participants mean age 5539 + 1268 38 met gsf criteria palliative care need patient selfreported data sparc questionnaire indicated participants rated score 3 1 domains 47 times likely meet gsf criteria frequently reported unmet needs fatigue 76 pain 71 anxiety 49 dependence 49 bowel bladder issues 38 participants aged 60 reported concerns loneliness p0001 anxiety p001 compared younger age groupsdiscussionour results reveal third cancer patients undergoing chemotherapy met gsf criteria palliative care need provides evidence large unmet need across various domains among patients may benefit introduction adjunctive palliative care lends support use similar tools hospital settingp22 financial psychosocial impact covid 19 cross sectional community based studymuhammad aamir anees1 prajna sharma2correspondence muhammad aamir anees1kanachur institute medical sciences mangalore india 2department community medicine kanachur institute medical sciences mangalore indiaintroductionin addition continuous rise cases mortality due covid19 lack information misinformation unverified news sources led mental health crisis like anxiety depression symptoms pandemic also led unemployment decrease family income hence study intend understand financial mental impact general populationmaterials methodologya cross sectional community based study conducted among general population sample size 100 calculated study participants selected using convenience sampling informed consent taken involving study pretested validated anonymous online questionnaire prepared sent using google forms collect information regarding sociodemographic variables financial status effect media daily life patient health questionnaire 9 phq9 used assess depression among data analyzed using proportions percentages independent sample t test statistical significance set p 005resultsof participants reported drastic decrease family income 19 mentioned pandemic affected availability basic resources like food water 27 reported family member lost job pandemic according phq9 scaling 7 total participants severely depressed 9 moderately severe depression 21 suffering moderate depression 36 mild depression 27 symptoms depression drastic reduction family income found responsible higher phq9 scoring statistically significant p 005 discussionthe pandemic significant financial psychosocial impact society recommend governments around world create emergency fund unprecedented situation like thisp23 health seeking behavior lifestyle people comorbidities covid19 pandemic pilot studymegha joy anilbindu scorrespondence megha joysree gokulam medical college research foundation venjarammoodu kerala indiaintroductioncovid 19 dramatically changed outpatient care followups delivered comorbid population dm htn cad fear covid infection kept patients away hospitals despite need followups poor clinical outcomes thus research questionhow health seeking behavior lifestyle comorbid population change covid pandemicmethodsa quantitative cross sectional study based nonrandom convenience sampling telephonic interviews among adults chronic diseases attending opds followed filling semistructured questionnaire google formsindependent variables age comorbidity gender educational leveldependent variables health seeking behavior lifestyle practicestatistics categorical data frequency percentagetest significance chi square testp005 significantresultsamong total 44 people average age 646 taken part study 636was dm 432 htn 159 cad 23 cancer 23 chronic liver disease rest conditions taking treatments least 2 years50 study participants regular follow ups scheduled among 432 faced delays since covid spread 386 followed medication since increase 182 telemedicine use among population compared null use precovid era can attributed fear getting infected covid19 reported 862 participants decrease 63 physical activity identifiedfood habits remained less sameconclusionthe fear covid infection made people avoid hospital visits costs practice attending clinicians physically reduced greatly got replaced telemedicine practice pandemic slight decrease physical activity seen population may make vulnerablep24 health service use associated costs attributable diabetes mitchelstown cohort studypatrick walsh1 kate oneill2 patricia kearney2correspondence patrick walsh1school medicine university college cork 2school public health university college corkintroductionthe number people diabetes increasing globally evidence rising medical expenditure per person growth economic burden will continue accurate cost illness estimates needed inform national policy identify potential cost savingsaimto estimate health service use costs attributable diabetesmethodsa sample middleaged adults 50 years mitchelstown cohort study collected 20162017 analysed diabetes defined using selfreport doctordiagnosis hba1c fasting plasma glucose levels health service use previous 12months included number general practitioner gp visits emergency department visits hospital admissions outpatient visits day procedures multivariable negative binomial regression used estimate association diabetes frequency visits frequency visits applied unit costs health service calculating mean costs per person without diabetesresultsof 1 332 patients analysed prevalence diabetes 104 95ci89 122 diagnosed 74 95ci61 89 undiagnosed 31 95ci23 42 diabetes associated 49 increase gp visits diabetes associated additional hospital admissions emergency department visits outpatient visits day procedures annual mean cost health service use among diabetes 1 59780 per person compared 1 35267 withoutconclusionwhile diabetes associated additional gp visits associated additional service use secondary care structured diabetes management primary care may contribute reduced health service use costs attributable diabetesp25 histomorphometric changes lung lymphoid follicles young rats experimental alloxan hyperglycemiatoufik abdulrahman andrew awuah wireko tetiana teslykcorrespondence toufik abdulrahmansumy state university sumy ukraineintroductiondiabetes remains global problem today leading disability disability deathmethodsthe studies performed 48 white laboratory rats sexes experimental animals divided two series experimental intact experimental group divided subgroups first term hyperglycemia 30 days second 60 days third 90 days fourth 120 days experimental simulations hyperglycemia alloxan monohydrate used perimeter lymphoid follicles plf measured level glucose glycosylated hemoglobin hba1c venous blood rats determined slaughter animalsresultsthe level glucose blood experimental animals 30 120 days ranged 133 01 193 02 mmol l end second month experiment level hba1c ranged 71 0 05 86 008 intact group level glucose blood within normal limits 30th day plf intact experimental animals 4493 082 m 449 017 m respectively 60 days hypertrophy pulmonary lymphoid follicles pronounced vascularization noted comparison intact animals plf index 23 times higher involute changes lymphoid follicles malnutrition observed intact animals day 90 experimental animals age plf increased 13 times compared 60th day day 120 experiment plf experimental animals increase 38 times compared intact animalsdiscussionagainst background chronic experimental hyperglycemia young animals developed hypervascularization hypertrophy pulmonary lymphoid follicles thereby causing obstruction lower respiratory tractp26 il6 synthesis hela cancer cells synthesis modulation polyphenols taxifolin example albina zagidullina vladimir rogovskycorrespondence albina zagidullinapirogov russian national research medical university moscow russiaintroductioncancer one leading causes death people worldwide researchers around world try find different ways impede tumor growth cancer progression one latest news area possibility natural polyphenols prevent treat cancer research decided check possible action polyphenols taxifolin immune microenvironment cancer cellsmaterialsfor purpose used hela cells cultivated culture media bovine serum + dmem placed 10000 cells well plate supernatant taken well elisa procedure elisa used il6 determination cell culture analysis provided usage graphpad prismresultsthere relatively high secretion il6 hela cells 271 pg ml culture media taxifolin raised concentration il6 culture media 271 11 5 pg ml 301 18 pg mldiscussionon step research get intermediate results showed presence natural polyphenol cell culture rises production il6 plays important role tumor suppression increasing concentration il6 can stimulate inflammatory response can lead domination tumor immune rejection processes tolerance however research work still proceeds comparison polyphenols curcumin egcg resveratrol will done precise evaluation polyphenols role cancer treatment prevention possibilitiesp27 improved cookstove interventions reduce household ambient air pollution among global poorest communities scoping reviewjessica langevin1 megan davis1 eunice phillip1 nitya kumar2 vincent jumbe3 mike clifford4 aisling walsh1 sarah jewitt4 joseph mfutsobengo3 maria beard4 debbi stanistreet1correspondence jessica langevin1royal college surgeons ireland dublin ireland 2royal college surgeons irelandbahrain busaiteen bahrain 3university malawi zomba malawi 4university nottingham nottingham united kingdomintroductioneach year combined effects household ambient air pollution haap lead approximately seven million premature deaths globally contributes number cardiovascular respiratory diseases burden highest low middleincome countries major source haap combustion fossil fuels cooking lighting despite anticipated increase access clean cooking next twenty years absolute numbers africa access clean fuels expected increase recognizing communities unlikely able afford expensive cooking technologies important identify affordable stove interventions reduce impact haap among poorest communitiesobjectivesto explore evidence relation cookstoveintervention options available global poorest communities reduce haap characteristics eg type cost availability health impact interventionsmethodsthis review followed joanna briggs institutes framework biomass stove intervention studies conducted 2014 date africa english included four reviewers conducted preliminary screening followed fulltext screening 20 double screened uncertainties resolved discussion data extraction completed remaining studies allresultsevidence relation stove type efficiency emissions safety price based clean cooking catalogue data recorded compared field results available reduction hap health outcomes summarized data available also report availability accessibility quality included studies assessedconclusionthe outcome review along additional evidence literature will used develop tool kit guide haap interventions poorest communities globallyp28 incidence early complications modified radical mastectomy breast cancermaryam ehtesham1 talal almas1 absam akbar2 muhammad kashif khan3correspondence maryam ehtesham1royal college surgeons ireland dublin ireland 2aga khan university karachi sindh pakistan 3surgical oncology maroof international hospital islamabad islamabad capital territory pakistanintroductionmodified radical mastectomy primary surgical treatment breast cancer often associated seroma formation postoperatively study aims address possibility complication along likelihood developing wound infection postoperativelymethodspatients met selection criteria identified randomly selected age patients stage breast cancer complications observed six weeks recorded data collected input analysed using spss version 210resultsof 65 patients selected 3 patients 46 developed wound infection 19 patients 2923 seroma formation additional 18 patients 2769 stage ii breast cancer seroma formation compared merely 1 patient 154 stage breast cancer furthermore 3 patients stage ii breast cancer developed wound infection none patients stage breast cancer developed complicationdiscussionmodified radical mastectomy invasive surgical procedure can elicit myriad complications including seroma formation wound infection studys findings consistent national studies regards incidence seroma formation aftermath modified radical mastectomy nevertheless studies larger sample sizes better controlarms needed order determine true incidence postoperative complicationsp29 induced pluripotent stem cells potential treatment type 1 diabetesryan ahn1 nidheesh dadheech2 james shapiro2correspondence ryan ahn1royal college surgeons ireland dublin ireland 2department surgery university alberta edmonton canadaintroductiontype 1 diabetes mellitus metabolic disease characterized autoimmune destruction pancreatic islets causing lifelong insulin deficiency insulin remains mainstay treatment type 1 diabetes tremendous strides cell replacement therapy via allogeneic whole pancreas islet transplantation methods limited due scarcity tissue requirement chronic immunosuppression induced pluripotent stem cells ipscs ability regenerate differentiate specialized cells due genetic reprogramming yamanaka factors oct3 4 sox2 cmyc klf4 methodsperipheral blood mononuclear cells pbmcs taken patient surgicallyinduced diabetes cells cultured expansion reprogrammed human ipscs introduction yamanaka factors via retroviral vector sendai virus ipscs expanded 8 passages tested pluripotency genetic analysis immunofluorescenceresultsgenetic analysis performed via rtpcr followed gel electrophoresis demonstrating presence klf4 oct4 sox2 cmyc however also confirmed persistence genetic material viral vector immunofluorescence verified presence oct4 sox2 also proving expression pluripotency markers nanog ssea4 tra160 tra181 discussioncharacterization cells confirmed newly created ipscs truly pluripotent differentiation cells yield functional patientspecific specialized cells including functioning pancreatic beta cells tissue engineering ipscs potentially future applications treatment possible cure type 1 diabetesp30 interrater variability manual feature selection retinal vascular optical coherence tomography imagingtiffany yeretsian1 yu li2 joel ramjist2 jillian cardinell2 nhu nguyen2 yuta dobashi3 chaoliang chen2 victor yang2correspondence tiffany yeretsian1royal college surgeons ireland dublin ireland 2ryerson university toronto canada 3university toronto toronto canadaintroductionthe movement towards quantitative diagnostic biomarkers medical imaging shown increasing promise disease identification early detection particularly true mature imaging modalities including optical coherence tomography angiography octa octa imaging can provide vital information regarding state morphological features vascular networks particularly used regularly examination retinal vascular networks potential implications direct monitoring window cerebrovascular networksmethodsin preliminary study 7 individual raters familiar retinal octa imaging presented series 40 images maximal vessel diameter basis evaluations branchpoint count tortuosity determined semiautomated manual inputs variability recorded measures raters examinedresultsthe preliminary results demonstrate variability one may expect standard clinical dataset potential hurdle may need overcome determining ground truths training data supervised neural networksdiscussionfeatures vascular fraction fractal dimension branchpoint count tortuosity maximal vessel diameter hold particular promise important biomarkers interest however many current methods determining metrics semiautomated manual requiring user judgement input thus subjective nature user input may result significant interrater variability potentially causing quantitative evaluation left variable proper diagnostic accuracy however demonstrated moreover emergence new automated methods employed particularly use machine learning understanding variance key especially regards supervised learning methods groundtruths may determined rater datap31 investigating genetic changes macrophages mediated il10therese lynn remsha afzal claire mccoycorrespondence therese lynnroyal college surgeons ireland dublin irelandmacrophages play essential role regulation inflammation persistent inflammation however macrophages may cause severe tissue damage implicated number inflammatory autoimmune diseases multiple sclerosis conversely macrophages can also adopt antiinflammatory phenotype producing antiinflammatory mediators potentiate tissue regeneration repair il10 known inducer antiinflammatory phenotype aim study interrogate genetic changes macrophages induced il10 decipher mechanisms promote antiinflammatory state will aid rationale harnessing macrophages therapeutically help elucidate role disease processes murine bonemarrow derived macrophages harvested treated lps il10 following 24 hour exposure affymetrix array conducted project involved systematically analysing array identify gene completing literature search using pubmed interrogate genes potential relevance four topics related macrophage function il10 signalling mitochondrial metabolism glucose metabolism multiple sclerosis analysis array showed 132 genes significantly upregulated whereas 142 significantly downregulated upon il10 exposure versus control macrophages following exclusion duplicates 97 unique entries identified 85 genes 88 human homologs 94 genes 97 protein coding following systematic literature review 40 genes yielded relevant publications following review seven genes remaining 57 relevant publications across four topics namely igg receptor fcgr2b membrane glycoprotein neuroregulin1 transcription factors nfil3 bhlehe40 metalloprotease steap4 hormone adrenomedullin enzyme arginase2 research serves reference study identifying key genes associated antiinflammatory macrophage phenotype following il10 stimulation seven genes interest highlight key mechanisms macrophage orchestrates essential function represent potential areas future therapeutic benefitp32 investigating impact covid19 breastfeeding rates support structures michael garron hospitaldesiree dsouza1 jennifer bordin2 rebecca sy tyli3 soraya visram4 melissa tai5correspondence desiree dsouza1graduate entry medicine royal college surgeons ireland dublin ireland 2michael garron hospital toronto east health network toronto canada 3health science program mcmaster university hamilton canada 4michael garron hospital toronto east health network university toronto toronto canada 5michael garron hospital toronto east health network university toronto toronto canadaintroductionthe breastfeeding clinic michael garron hospital plays pivotal role maintaining hospitals breastfeeding friendly designation pandemic forced closure clinic midmarch midjune 2020 inhospital lactation consultations also limited assessed impact closure breastfeeding clinic breastfeeding rates sought identify main challenges breastfeeding mothers confirmed suspected cases covid19methodswe used explanatory sequential mixedmethod approach breastfeeding rates marchmay 2019 compared 2020 followed retrospective telephone service evaluation 3 mothers tested positive covid19 100 response rate 18 investigation 42 response rate reflexive thematic analysis qualitative data conducted identify barriers facilitators breastfeedingresultsthere significant differences breastfeeding initiation rates however adjusted breastfeeding rates account infants received one feed human milk documented medical reason significantly lower march april may 2020 march april 2020 95 mothers intended breastfeed 91 provided breastfeeding education yet adjusted breastfeeding rate 65 retrospective telephone survey identified anxiety virus reduced lactation consultation isolation major barriers breastfeeding facilitators included video lactation consultation increased time babydiscussionwhile breastfeeding initiation successful continuity impaired potentially due reduced support postpartum result lockdown pandemic presented compounding difficulties breastfeeding work enabled us learn directly patients experience prepare similar situations broaden access lactation servicesp33 possible predict effects metabolic surgeryizabela karpiska1 joanna choma1 alicja dudek1 piotr maczak1 magdalena szopa2 piotr major1correspondence izabela karpiska12nd department general surgery jagiellonian university medical college krakow poland 2department metabolic diseases jagiellonian university medical college krakw polandintroductionbariatric surgery proven efficient treatment obesity type 2 diabetes mellitus t2dm despite detailed qualification every patient achieved desirable outcome t2dm remission intervention recently diabetter roberts scores developed predict diabetes remission bariatric surgeryaimto validate compare performance diabetter roberts scores predictors diabetes remission 1 year surgical treatmentmaterial methodsthe retrospective analysis included consecutive patients t2dm underwent rouxeny gastric bypass rygb sleeve gastrectomy sg 2009 2017 single tertiary referral center completed 1year followup diabetter roberts scores calculated patient score relationship diabetes remission assessed using logistic regression discrimination evaluated area receiver operating characteristic auroc whereas calibration hosmerlemeshow testresultsout 252 patients enrolled study 150 595 women whereas 102 405 men median age 48 years 4683 patients underwent sg whereas 5317 rygb t2d remission rate reached 905 median preoperative a1c 675 preoperative bmi 4539 kg m2 decreased 58 3309 kg m2 respectively 1 year ewl surgery amounted 534 either diabetter roberts score predictive diabetes remission logistic regression analysis 051 p00001 193 p00031 respectively diabetter score presented excellent discrimination power auroc 081 p00001 whereas roberts score poor discrimination auroc067 p00001 scores demonstrated statistically good calibrationconclusionsboth diabetter roberts scores can used preoperative assessment diabetes remission bariatric surgery diabetter score seems accurate diarem score predicting metabolic outcomes bariatric surgeryp34 operating theatre practices microbes air postoperative infectionsultan abukhodair1 josh de marchi2 anna heaney2 trudi nelson3 aoife d kearney4 abeeda butt2 hilary humphreys4 arnold hill1 2correspondence sultan abukhodair1royal college surgeons ireland dublin ireland 2department surgery beaumont hospital dublin ireland 3beaumont hospital dublin ireland 4department clinical microbiology royal college surgeons ireland education research centre beaumont hospital dublin irelandintroductionsurgical site infections ssi account 20 nosocomial infections intraoperative infection prevention control ipc measures including adherence aseptic technique observed adherence ipc practices healthcare workers surgical procedures sampled air airborne bacteria particlesmethodsgeneral surgical procedures audited compliance ipc measures including appropriate use personal protective equipment antibiotic prophylaxis three weeks six procedures air sampling aes chemunes samplair lite air sampler columbia blood agar plates incubated 24 h four procedures airborne particles also measured using particlescan protm airborn particle counter patients followed outpatients telephone seven days postprocedureresultsa total 31 operations observed 25 31 806 clean wounds 3 31 96 cleancontaminated 1 31 32 contaminated 2 31 64 infected 100 healthcare workers wore hats 706 wore masks 505 wore scrubs 22 709 patients received appropriate prophylaxis 2 64 received pre intraoperative prophylaxis 7 226 receive prophylaxis airborne bacterial counts 1274 cfu m3 mean 34 cfu m3 colony counts number people st josephs high compared beaumont airborne particle counts 1m 25146 mean 755 5m 010 mean 44 26 31 available follow ssidiscussionmost procedures low risk ssi hence ssi compliance ipc generally good larger study required correlate ssi ipc bacterial particle countsp35 patient experiences remote monitoring pathway covid19courtney cheng1 lora appel2 andrea scrivener3 christopher smith3correspondence courtney cheng1school medicine royal college surgeons ireland dublin ireland 2openlab university health network toronto canada 3michael garron hospital toronto east health network toronto canadaintroductionin response covid19 outbreak michael garron hospital developed covidcare remote monitoring pathway provide timely clinical evaluation management patients suspected confirmed covid19 remote monitoring increasingly used limited data exist patients experiences pathways managing covid19 study aims describe patients experiences covidcare specifically two patient populations medium highlevel alerts return emergency department ed successfully managed home b returned ed admittedmethodssemistructured phone interviews conducted transcribed analysed using grounded theoryresultsacross 35 interviews response rate 66 three main themes identified program provided emotional support sense security reduced feelings depression loneliness decreased fear anxiety informative taught patients covid19related precautions instructed patients selfmonitor covid19 symptoms informed patients selfcare coping covid19 motivated patients selfmonitor selfmanage facilitated selfmanagement prompted selfmanagement encouraged selfmonitoring patients groups also reported nurses times urging go ed despite feeling able manage home patients group b returned ed issues directly related covid19discussionthe covidcare pathway wellreceived interviewed patients groups identified tendency nurses recommend ed assessment worsening symptoms however patients group b returned ed issues directly related covid19 limiting analysis advice may affected differently research explore tendency covidcare pathway recommend ed assessment improve efficiency applicability remote monitoring programsp36 patterns metastatic disease stage iv alkrearranged nonsmall cell lung cancer patientssimren chotai1 karmugi balaratnam2 luna jia zhan2 devalben patel2 wei xu2 catherine brown2 katrina hueniken2 geoffrey liu2correspondence simren chotai1royal college surgeons ireland dublin ireland 2princess margaret cancer centre toronto canadaintroductionanaplastic lymphoma kinase alk gene rearrangements occur 24 nonsmallcelllungcancers nsclc study aims determine patterns metastatic disease rare stage iv alkrearranged nsclc patients limited realworld data topicmethodsin cohort stage iv alkrearranged nsclc patients princess margaret cancer centre comprehensive canadian cancer centre manual data ion performed electronic patient records supplemented patientreported demographic survey data descriptive summary statistics performedresultsof 105 stage iv alkrearranged nsclc patients 54 female median range age 60 3192 years 31 caucasian 40 asian 75 lifetime neversmokers 75 de novo stage iv median range number metastatic sites 1 16 baseline 1 year 2 110 sites baseline 53 patients 1 metastatic site 27 2 sites 10 3 sites 10 46 sites baseline 1 year baseline proportion patients bone metastases risen 32 43 brain 25 37 liver 11 14 lung 17 28 adrenal 6 11 pleuralpericardial disease 44 60 alkrearranged nsclc patients exhibited unusual areas metastases including leptomeningeal choroidal kidney peritoneum pancreas adnexadiscussioncompared historical local cohorts general nsclc patients alk+ nsclc patients younger likely lifetime neversmokers asian descent greater prevalence pleuralpericardial disease bone brain metastases presenting unusual patterns metastatic spread stage iv alk+ nsclcs form distinct clinical demographic patient group compared general nsclc population evaluating metastatic patterns can provide better understanding disease progressionp37 psammocarcinoma ovary systematic reviewilia mihaylov1 diana strateva2 angel yordanov2correspondence ilia mihaylov1medical university pleven pleven bulgaria 2department gynecologic oncology medical university pleven pleven bulgariapsammocarcinoma rare subtype serous epithelian neoplasms literature commonly described ovaries peritoneum characterized massive psammoma body formation low grade cytologic features invasiveness clinical behavior similar serous borderline tumorswe performed search pubmed sciencedirect following terms ovary psammocarcinoma ovarian cancer psammocarcinoma total 211 results came back beginning october 2020 excluded studies reports cancer localization type duplicating articles paid special attention patients age cancer staging type surgery chemotherapy recurrenceafter careful evaluation results 44 cases psammocarcinoma ovary discovered median age 528 years 1973 common stage figo iiib 11 patients stage iii common 24 cases 17 cases unknown staging surgical interventions differ many cases age stage cancer circumstances differ however common radical hysterectomy bilateral salphingooophorectomy omentectomy cases taking biopsy peritoneum lymph node dissection performed cases debulking order protect natal capabilities common adjuvant chemotherapy includes carbapenem paclitaxel pc therapy 7 patients one female underwent neoadjuvant pc chemotherapy finally 7 24 patients followup either died disease recurrenceovarian psammocarcinoma rare aggressive oncological condition total 44 patients found pubmed sciencedirectcom many instances poor description case yet late diagnosing disease aggressive nature factp38 radiomics analysis pet ct findings fludeoxyglucose 18f biomarker differentiation spondylodiscitis bone metastasis patients focal lesions spinenatasa brisudova1 sona balogova2 iveta waczulikova1correspondence natasa brisudova1faculty mathematics physics informatics charles university bratislava 2faculty medicine charles university bratislavaintroductionearly initiation targeted treatment can prevent possible irreversible neurological complications spondylodiscitis sd spinal metastases met differentiation may diagnostic problem especially early stages aim identify radiometric characteristics pet fdg helping distinguish sd metmethodsretrospective analysis 31 second higherorder radiometric elements 60 patients confirmed sd n 30 met various malignancies n 30 total 40 sd findings 40 met findings analyzed using lifex freeware allows calculation conventional textural shape elements diagnostic images clinical characteristics patients nonparametric wilcoxon rank sum test compared using statistical software rstudio acceptable diagnostic accuracy tested using roc curve furthermore predictive ability distinguish sd met tested using machine learning three methods tested multiple logistic regression random forest support vector machines three different ways selecting training test data kfold crossvalidation leave oneout crossvalidation train test split resultswhen sd met distinguished 24 31 radiometric elements confirmed statistically significant p 05 9 24 auc 80 diagnostic accuracy highest values reached parameters glzlm_zp cutoff 038 auc 8325 ngldm_contrast cutoff 017 auc 847 glrlm_glnu cutoff 461 auc 888 machine learning effective method random forest cutoff 028 auc 9861 method data selection train test splitconclusionsthe results confirm radiomatic analysis machine learning possible direction distinguishing sd met pet ct fdg support validationp39 reninangiotensinaldosterone system target facilitating sinus rhythm maintenance electrical cardioversion hypertensive atrial fibrillation patientsbaiba kokina1 oskars kalejs2correspondence baiba kokina1faculty medicine riga stradins university riga latvia 2department internal diseases riga stradins university latvian centre cardiology pauls stradins clinical university hospital riga latviaintroductionsinus rhythm maintenance electrical cardioversion ecv remains challenging comorbid atrial fibrillation af patients arterial hypertension ah established role pathophysiologically linked pressor effects reninangiotensinaldosterone system raas upregulation nonantiarrhythmic drug nonaad upstream therapies including raas inhibition angiotensinconverting enzyme inhibitors aceis angiotensin receptor blockers arbs mineralocorticoid receptor antagonists mras come focus showing heterogeneous results study evaluates whether convincing raas inhibition aceis arbs combination mras can add benefit aad therapy facilitating sinus rhythm maintenance ecv af patients pharmacologically controlled ahmethodsthe study conducted among af patients successful ecv latvian centre cardiology additional inclusion criteria pharmacologically controlled ah class ic iii aad prescription restricting specific medication intake baseline interview 1 3 6 9 12month followup conducted medication effectiveness evaluated using ms excel spss statistics calculating odds ratios ors 95 confidence intervals cis significance level 005results99 patients included among participants using raas inhibitor 202 af recurrence rate comprised 650 present raas inhibitor 798 therapy demonstrated recurrence rate 481 534 333 relapses acei arb concomitant acei arb mra intake respectively compared nonuse presence raas inhibitor reduced af recurrence 501 0499 95ci 01801383 p0181 acei arb intake 382 0618 95ci 02161773 p0371 combined acei arb mra use 731 0269 95ci 00740979 p0046 discussionraas inhibition demonstrated therapeutic potential adjunctive aads showing improved sinus rhythm maintenance tendency pharmacologically controlled hypertensive af patients statistically significant effect demonstrated concomitant acei arb mra intake highlighting effects beyond blood pressure reduction findings supportive mra use af patients ah yet primarily emphasized groupp40 tamoxifen doxorubicin hydrochloride chemotherapy vivo efficacy different doses formulations treatment schemesvityala yethindra1 tugolbai tagaev2 cholpon dzhumakova3 asel namazbekova4correspondence vityala yethindra1international higher school medicine international university kyrgyzstan bishkek kyrgyzstan 2department public health healthcare ik akhunbaev kyrgyz state medical academy bishkek kyrgyzstan 3department gastroenterology national center oncology hematology bishkek kyrgyzstan 4department cancer registry national center oncology hematology bishkek kyrgyzstanintroductionthe use combination therapy cancer treatment helps decrease treatment doses consequently reduces nonspecific cytotoxicity resistance aimed investigate whether liposomal nonliposomal doxorubicin dox alone combination tamoxifen tam exhibit antitumor effectsmethodswe assessed efficacy various anticancer treatment regimens development walker 256 tumors white rats 32 animals weighing 250300 g dox 5 mg kg administered either nonformulated formulated liposomes alone combination tam 05 mg kg intraperitoneally following two different regimens prophylaxis daily 15 days + treatment daily 5 days treatment daily 5 days prophylaxis + treatment regimen also used context combination therapy lower dose tam 025 mg kg shorter treatment period 3 days tumor growth recorded data presented mean standard deviation students ttest used twogroup comparisons p005 considered significantresultsthe administration liposomal dox 5 days tumor inoculation led significant inhibition tumor growth 17 days start experiment 43 versus control group noteworthy tumor growth suppression similar context dox monotherapy liposomes combination therapy combination liposomal dox tam effective approach suppressing tumor growth via prophylactic + treatment regimen significant difference tumor growth curves observed day 5 growth inhibition 32discussionthe effective anticancer approach administration liposomal dox combination tam prophylactic + therapeutic regimen provided considerable safety significant inhibition tumor growthp41 association maternal micronutrients supplementation child birthweight saad abualela hospital suba teaching hospital khartoum sudan 2019arwa alsharief1 heitham awadalla2correspondence arwa alsharief1university khartoum faculty medicine khartoum sudan 2university khartoum faculty medicine department community medicine khartoum sudanintroductionbirth weight strong predictor child health development influenced many factors including maternal health micronutrients supplementation pregnancy beneficial improving maternal health maybe potential benefit fetal outcomes study aims assess effect antenatal multiple micronutrients supplements infant birth weight compared routine ironfolate supplementsmethodsthis cross sectional study 223 women chronic illnesses conducted saad abualela suba university hospitals khartoum sudan data collected structured interviews birth weights recorded measured midwives women asked sociodemographic data health factors height weight measured classify bmi information antenatal micronutrients intake status type supplements duration intake also collected data analysed using spss 21resultsof 223 women participated study 136 live born children low birth weight mean 289 056 proportion low birth weight higher female male infants total 6878 mothers consumed multiple micronutrients n152 2081 ironfolate supplements n46 small nonsignificant increase birth weight mothers receiving multiple micronutrients compared ones receiving ironfolic acid supplements 294 056 vs 286 044 kg respectively p0 25 additional benefit elicited multiple micronutrients reducing risk low birth weight surprisingly higher group 138 ironfolate group 131 conclusionin sudan multiple micronutrients confers additional benefit ironfolic acid supplements reducing risk low birth weight relatively healthy mothers however resulted nonstatistically significant increase mean birth weightp42 utilization patterns drugs used treatment rheumatoid arthritis tertiary care hospital omanmoosa allawati1 sanad almalki1 aly abdelrahman2correspondence moosa allawati1college medicine health sciences sultan qaboos university seeb oman 2department pharmacology clinical pharmacy college medicine health sciences sultan qaboos university seeb omanintroductionrheumatoid arthritis ra autoimmune rheumatic disease ard different synovial joints affected patients prescribed antirheumatic agents symptomatic treatment delay progression disease agents include glucocorticoids diseasemodifying antirheumatic drugs dmards biological medications nonsteroidal antiinflammatory drugs nsaids aim study identify utilization patterns glucocorticoids dmards prescribed ra patients visited sultan qaboos university hospital squh methodsa retrospective study conducted data 200 ra patients visited squhs rheumatology clinic noted data included patients data besides antirheumatic agents prescribed last one two visits data accessed using hospitals system noted types data variables collected records doses routes administration general prescription patterns according age gender data analyzed using spssv23 important statistical associationsresultsout 200 ra patients 179 females 21 males 370 prescribed two medications threequarters patients 770 prescribed dmards glucocorticoids prescribed 495 patients classes drugs commonly prescribed oldest age group 65 years old patients 895 prescribed oral medicationsdiscussionthe data study showed differences prescription patterns antirheumatic drugs among genders age groups methotrexate commonly prescribed medication accordance previous studies study help doctors know utilization patterns antirheumatic drugs work needed regarding topic oman current researches outdatedadditional informationpublishers notespringer nature remains neutral regard 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corneal immune cells increased patients multiple sclerosis transl vis sci technol 2021 apr 1 10 4 19 doi 101167 tvst10419abstractpurpose corneal confocal microscopy ccm ophthalmic imaging technique used identify increased corneal immune cells patients immunemediated peripheral neuropathy given multiple sclerosis immunemediated etiology compared corneal immune cell ic density nearnerve distance different subtypes patients multiple sclerosis ms controlsmethods blinded crosssectional study conducted tertiary hospital patients clinically isolated syndrome cis n 9 relapsingremitting multiple sclerosis rrms n 43 secondary progressive multiple sclerosis spms n 22 control subjects n 20 underwent ccm total mature immature corneal ic density nearest nerve distance quantifiedresults total ic density higher patients ms p 002 rrms p 001 spms p 004 cis p 099 compared controls immature ic density higher patients ms p 003 rrms p 002 spms p 010 cis p 099 compared controls mature ic density p 015 differ patients ms controls immature ic nearnerve distance significantly greater patients ms p 0001 rrms p 0007 spms p 0002 compared controls immature ic density correlated symbol digit modalities test r 0281 p 002 nearnerve distance correlated expanded disability status scale r 0289 p 0005 conclusions vivo ccm demonstrates increase immature ic density nearnerve distance patients ms observations merit studies assess utility ccm assessing neuroimmune alterations mstranslational relevance multiple sclerosis immunemediated neurodegenerative disease dendritic cells mediate communication innate adaptive immune systems used vivo ccm show increased corneal ics suggest may act imaging biomarker disease status patients mspmid34003997 doi101167 tvst10419,0.0
tractspecific mri measures explain learning recall differences multiple sclerosis brain commun 2021 apr 1 3 2 fcab065 doi 101093 braincomms fcab065 ecollection 2021abstractcognitive difficulties common key concern people multiple sclerosis advancing knowledge role white matter pathology multiple sclerosisrelated cognitive impairment essential occur early disease implications early intervention consequently crosssectional study asked whether quantifying relationships lesions specific white matter structures better explain coexisting cognitive differences whole brain imaging measures forty participants relapseonset multiple sclerosis underwent cognitive testing mri 3 tesla classified cognitively impaired n 24 unimpaired n 16 differed across verbal fluency learning recall tasks corrected intelligence education corrected pvalues 0007004 relationships lesions white matter characterized across six measures conventional voxelbased t2 lesion load whole brain tractogram load lesioned volume whole tractogram volume whole bundle volume bundle load lesioned volume whole bundle volume tractometry diffusiontensor high angular resolution diffusion measures sampled bundle streamlines lesionometry diffusion measures sampled streamlines traversing lesions tractspecific measures extracted corpus callosum segments genu isthmus striatoprefrontal parietal pathways superior longitudinal fasciculi sections ii iii white matter measuretask associations demonstrating least moderate evidence null hypothesis bayes factor threshold 02 examined using independent ttests covariate analyses significance level p 005 tractspecific measures significant predictors pvalues 005 taskspecific clinical scores diminished significant effect group categorical predictor story recall isthmus bundle load figure recall right striatoparietal lesionometry design learning left superior longitudinal fasciculus iii volume lesion load explained difference list learning whereas letter fluency associated imaging measures overall tractspecific measures outperformed global lesion tractogram load measures variation regional lesion burden translated group differences tractspecific measures turn attenuated differences individual cognitive tasks structural differences converged temporoparietal regions particular influence tasks requiring visuospatialconstructional processing highlight measures quantifying relationships tractspecific structure multiple sclerosis lesions uncovered associations cognition masked overall tract volumes global lesion tractogram loads tractspecific white matter quantifications show promise elucidating relationships neuropathology cognition multiple sclerosispmid33959710 pmcpmc8088789 doi101093 braincomms fcab065,0.0
vaccination sarscov2 patients multiple sclerosis rev neurol 2021 apr 1 72 7 250260 doi 1033588 rn72072021097abstractintroduction recent availability sarscov2 vaccines raised concerns certain patient groups multiple sclerosis however currently publications provide information issue pooled information available safety efficacy vaccination sarscov2 patients multiple sclerosis without diseasemodifying therapydevelopment study consisted literature search focused types sarscov2 vaccines current status approval data available safety efficacy vaccines patients multiple sclerosis including new covid19 vaccines based search document designed taking account current evidence expert recommendations data safety efficacy sarscov2 vaccines patients multiple sclerosis however evidence exist suggest messenger rna mrna vaccines sarscov2 safe patients individuals therapies immunosuppressants might reduce effectiveness vaccines require scheduling administration preferably start treatment possibleconclusion data available make possible recommend mrna vaccines sarscov2 patients multiple sclerosis patients fingolimod cladribine alemtuzumab ocrelizumab rituximab vaccination prior initiation medication administration recommendable whenever possiblepmid33764494 doi1033588 rn72072021097,0.0
acute exudative polymorphous paraneoplastic vitelliform maculopathy aeppvm associated choroidal melanoma background report case acute exudative polymorphous paraneoplastic vitelliform maculopathy patient history choroidal melanoma metastases pancreas liver central nervous systemcase presentationa 63yearold patient history enucleation right eye due choroidal melanoma complained progressive visual loss followup visit fundoscopic examination revealed multiple small areas serous retinal detachment scattered throughout posterior pole ancillary tests confirmed diagnosis acute exudative polymorphous paraneoplastic vitelliform maculopathy aeppvm screening systemic metastases showed pancreatic hepatic central nervous system involvementconclusionswe describe rare case acute exudative polymorphous paraneoplastic vitelliform maculopathy considered patients without history melanoma vitelliform retinal detachments nevertheless previous reviews literature shown correlation aeppvm pancreatic metastasis,0.0
socioeconomic determinants global distribution multiple sclerosis ecological investigation based global burden disease data background socioeconomic factors may involved risk multiple sclerosis ms either indirectly confounding factors study two comprehensive indicators reflecting socioeconomic differences including human development index hdi prosperity index pi used assess impact factors worldwide distribution msmethodsthe data global ecological study obtained three comprehensive databases including global burden disease source ms indices united nations development programme source hdi legatum institute database pi ms indices including prevalence incidence mortality disabilityadjusted life years analyzed form age sexstandardized correlation regression analyses used investigate relationship hdi pi subsets ms indicesresultsall ms indices correlated hdi pi also found developed countries significantly higher prevalence incidence rates ms developing countries education governance pi gross national income expected years schooling hdi associated ms education significantly related ms indices p 001 developed developing countriesconclusionin general difference income socioeconomic development globally created landscape ms studied detail future studies,0.0
nrf2 aryl hydrocarbon receptor regulates il22 response cd4+ t cells j immunol 2021 mar 1ji1900656 doi 104049 jimmunol1900656 online ahead printabstractil17a il22 derived th17 cells play significant role mucosal immunity inflammation tgf il6 promote th17 differentiation however cytokines multiple targets identification screening additional molecules regulate il17a il22 responses certain inflammatory conditions great clinical significance study show cddoim specific nrf2 activator promotes il17a il22 responses murine th17 cells contrast cddoim inhibits il17a response multiple sclerosis patientderived pbmcs however nrf2 specifically regulates il22 response vivo nrf2 acts regulation antioxidant response element binding motifs target genes induce repress transcription promoter analysis revealed il17a rorc ahr genes several motifs showed nrf2 bound repressor arer2 rorc inhibited rorcdependent il17a transactivation luciferase reporter assay data showed cddoim regulated ahr promoter activity chromatin immunoprecipitation quantitative pcr data showed nrf2 bound ahr finally confirmed cddoimmediated induction il22 production cd4+ t cells abrogated cd4specific ahr knockout mice ahrcd4 ch223191 specific ahr antagonist inhibits cddoiminduced il22 production cd4+ t cells confirmed ahrdependent regulation collectively data showed nrf2 via ahr pathways regulated il22 response cd4+ t cellspmid33648937 doi104049 jimmunol1900656,0.0
abnormal dynamic pupillometry relates neurologic disability retinal axonal loss patients multiple sclerosis transl vis sci technol 2021 apr 1 10 4 30 doi 101167 tvst10430abstractpurpose assess alterations quantitative dynamic pupil responses light relation neurologic disability retinal axonal loss patients multiple sclerosis ms methods twentyfive patients relapsingremitting ms 25 healthy subjects included crosssectional study pupillary responses measured infrared dynamic pupillometry unit peripapillary retinal nerve fiber layer rnfl thickness measured spectraldomain optical coherence tomography neurologic disability assessed expanded disability status scale edss patients history optic neuritis within 6 months excluded right eyes assessed except 11 patients history unilateral eyes analyzed evaluate effect previous onresults initial pupil diameter p 0003 pupil contraction amplitude p 0027 lower patients ms compared healthy controls initial pupil diameter correlated edss score 0458 p 0021 rnfl correlated contraction latency 0524 p 0007 significant differences pupil parameters eyes without history fellow eyes 11 patients previous unilateral onconclusions dynamic pupillometry reveals significant alterations pupillary light reflex responses associated neurologic disability retinal axonal loss independent previous ontranslational relevance dynamic pupillometry simple noninvasive tool may useful detecting autonomic dysfunction patients mspmid34004008 doi101167 tvst10430,0.0
patient satisfaction quality counseling provided advanced practice nurses specialized multiple sclerosis quantitative analysis j neurosci nurs 2021 feb 17 doi 101097 jnn0000000000000578 online ahead printabstractbackground challenges dealing multiple sclerosis ms increased considerably recent years addition neurologists ms nurse specialists key management ms patients lack evidence regarding quality counseling methods data collection took place october 2018 march 2019 outpatient clinic university hospital quality counseling assessed using apnbq instrument contains 19 items can assigned 4 dimensions participants asked rate satisfaction scale 0 3 general satisfaction assessed scale 0 100 results participants n 110 rated quality counseling general satisfaction high mean sd structure quality dimension 264 044 satisfaction length frequency consultations 253 063 scored better outcome quality 199 062 process quality 213 060 conclusion overall high rate satisfaction quality counseling addition length frequency consultations ms patients particularly appreciated availability expertise ms nurse specialistspmid33605649 doi101097 jnn0000000000000578,0.0
anticentromere antibody induced immunization centromere protein freunds complete adjuvant may interfere mouse oocyte meiosis background anticentromere antibody aca member antinuclear antibody ana family recent studies found aca may associated oocyte maturation disorders however possible mechanism behind phenomenon remains unknown conducted study investigate whether aca penetrate living oocytes interfere oocyte meiosis mouse modelmethodswe divided mice three groups human recombinant centromere proteina human cenpa ha complete freunds adjuvant cfa used immunize mice study group ha + cfa mice injected cfa cfa group saline saline group respectively served controls immunization serum anticenpa antibody detected indirect immunofluorescence assay iift enzymelinked immunosorbent assay elisa chromosome alignment intracellular igg localization mi miistage oocytes investigated immunofluorescence analysisresultspositive acas successfully induced immunization cenpa cfa results showed serum level anticenpa antibody significantly higher ha + cfa group compared control groups marked increase chromosome misalignments mi mii oocytes ha + cfa group compared control groups however oocytes three groups showed intracellular antibody immunofluorescenceconclusionsthe development maturation oocytes impaired peripheral aca positive mice exhibited severe chromosomal misalignments metaphase meiosis however evidence acas entering oocytes observed thus underlying mechanism needs exploration,0.0
gene signature immune cell profiling highdimensional singlecell analysis covid19 patients presenting low t3 syndrome coexistent hematological malignancies background low t3 syndrome frequent patients admitted intensive care units critical illness pneumonia reported also patients covid19 hodgkin disease chronic lymphocytic leukemia analyzed clinical relevance low t3 syndrome covid19 patients particular associated hematological malignanciesmethodssixtytwo consecutive patients hospitalized first wave sarscov2 outbreak santandrea university hospital rome subdivided 38 patients group showing low levels ft3 24 patients group b normal ft3 serum values acute phase disease measured serum radiologic clinical disease severity markers scores search possible correlations ft3 serum values addition 6 covid19 patients 4 low t3 syndrome including 2 hematological malignancy 2 normal ft3 values performed highdimensional singlecell analysis mass cytometry multiplex cytokine assay gene expression profiling peripheral blood mononuclear cells pbmc resultslow ft3 serum values correlated increased absolute neutrophil count nlr dnlr ratios reduced total count cd3+ cd4+ cd8+ t cells low ft3 values correlated also increased levels inflammation tissue damage coagulation serum markers well sofa lipi tss scores cytof analysis demonstrated reduction effector memory terminal effector subtypes cd4+ t lymphocytes multiplex cytokine assay indicates mainly il6 ip10 mcaf changes associated ft3 serum levels particularly patients coexistent hematological malignancies gene expression analysis using nanostring identified four genes differently expressed involved host immune response namely cd38 cd79b ifit3 nlrp3conclusionsour study demonstrates low ft3 serum levels associated severe covid19 multiomics approach suggests t3 involved immune response covid19 coexistent hematological malignancy new possible t3 target genes patients identified,0.0
signal quality achilles#39 heel graph theory functional magnetic resonance imaging multiple sclerosis sci rep 2021 apr 1 11 1 7376 doi 101038 s41598021867920abstractgraphtheoretical analysis novel tool understand organisation brainwe assessed whether altered graph theoretical parameters observed multiple sclerosis ms reflect pathologyinduced restructuring brains functioning result reduced signal quality functional mri fmri cohort 49 people ms matched group 25 healthy subjects hs performed cognitive evaluation acquired fmri fmri measurement pearson correlationbased networks calculated graph theoretical parameters reflecting global local brain organisation obtained additionally assessed metrics scanning quality signal noise ratio snr fmri signal quality temporal snr contrast noise ratio cnr accordance literature found network parameters altered ms compared hs however significant link found cognition scanning quality snr differ cohorts contrast measures fmri signal quality significantly different explained observed differences gta parameters results suggest differences network parameters ms hs fmri reflect functional reorganisation brain rather occur due reduced fmri signal qualitypmid33795779 doi101038 s41598021867920,0.0
management sudden sensorineural hearing loss among primary care physicians canada survey study background sudden sensorineural hearing loss ssnhl medical emergency requiring immediate attention delayed treatment can lead permanent devastating consequences primary care physicians likely first presented ssnhl therefore crucial role recognizing initiating timely appropriate management aim study gain insight current knowledge practice trends pertaining diagnosis management ssnhl among family physicians canadamethodsan 18question survey targeting canadian family physicians marketed two physicianonly discussion groups social media platform facebook responses collected august 1st december 22nd 2019 aggregated quantifiedresults52 family physicians submitted responses 942 n 49 reported practice unilateral ssnhl warrants urgent referral otolaryngology 846 n 44 reported unilateral suddenonset hearing loss warrants urgent referral audiological testing 731 participants n 38 reported attempt differentiate conductive sensorineural hearing loss presented unilateral acute suddenonset hearing loss 615 n 32 rely tuning fork tests inform management decisions compared 942 n 49 relying case history 885 n 46 otoscopy 769 n 40 prescribe corticosteroids presented confirmed unilateral ssnhlconclusionthe majority family physicians study make appropriate referral treatment decisions management ssnhl understanding medical emergency tuning fork tests underutilized informing management decisions compared means differentiating conductive sensorineural hearing loss research needed understand family physicians prescribe corticosteroids treatment ssnhl may identify gaps knowledge inform improvements clinical protocolgraphical abstract,0.0
identification bloodderived candidate gene markers new 7gene diagnostic model multiple sclerosis background multiple sclerosis ms central nervous system disease high disability rate modern molecular biology techniques identified number key genes diagnostic markers ms etiology pathogenesis ms remain unknownresultsin study integration three peripheral blood mononuclear cell pbmc microarray datasets one peripheral blood t cells microarray dataset allowed comprehensive network pathway analyses biological functions msrelated genes differential expression analysis identified 78 significantly aberrantly expressed genes ms functional enrichment analysis showed genes associated innate immune responseactivating signal transduction p 00017 neutrophil mediated immunity p 0002 positive regulation innate immune response p 0004 il17 signaling pathway p 0035 immunerelated signaling pathways addition network msspecific proteinprotein interactions ppi constructed based differential genes subsequent analysis network topology properties identified upregulated cxcr4 itgam actb rhoa rps27a uba52 rpl8 genes hub genes network also potential biomarkers ms rap1 signaling pathway leukocyte transendothelial migration rtqpcr results demonstrated cxcr4 obviously upregulated actb rhoa itgam downregulated ms patient pbmc comparison normal samples finally support vector machine employed establish diagnostic model ms high prediction performance internal external datasets mean auc 097 different chip platform datasets auc 093 conclusionthis study provides new understanding etiology pathogenesis ms facilitating early identification prediction ms,0.0
society cardiovascular magnetic resonance 2019 case week series abstractthe society cardiovascular magnetic resonance scmr international society focused research education clinical application cardiovascular magnetic resonance cmr scmr web site https wwwscmrorg hosts case series designed present case reports demonstrating unique attributes cmr diagnosis management cardiovascular disease clinical presentation followed brief discussion disease unique role cmr disease diagnosis management guidance nature somewhat esoteric instructive publication provide digital archive 2019 case week series means enhancing education interested cmr means readily identifying cases using pubmed similar search engine,0.0
impact aerobic exercise clinical magnetic resonance imaging biomarkers persons multiple sclerosis exploratory randomized controlled trial j rehabil med 2021 mar 19 doi 102340 165019772814 online ahead printabstractbackground insufficient knowledge aerobic exercise impacts disease process multiple sclerosis characterized accumulation white matter lesions accelerated brain atrophyobjective examine effect aerobic exercise neuroinflammation neurodegeneration magnetic resonance imaging clinical measures disease activity progression persons multiple sclerosispatients methods exploratory 12week randomized control trial including intervention group n 14 12 weeks aerobic exercise twice weekly control group n 14 continuation usual lifestyle primary outcomes magnetic resonance imaging measures lesion load brain structure volume change secondary outcomes included disability measures blood cytokine levels cognitive tests patientreported outcomesresults effects aerobic exercise whole brain grey matter atrophy minor surprisingly observed effect volume atrophy selected brain substructures heterogeneous putaminal posterior cingulate volumes decreased parahippocampal gyrus volume increased thalamus amygdala volume remained active lesion load count decreased however apart weak improvements walking speed brainderived neurotrophic factor levels effect aerobic exercise clinical cognitive patientreported outcomesconclusion results suggest aerobic exercise persons multiple sclerosis positive effect volume substructures brain possibly indicating slowing neurodegenerative process regions negative impact volume substructures unclear implications research needed determine whether slight decrease active lesion volume count implies antiinflammatory effect aerobic exercise exact significance heterogeneous results volumetric assessmentspmid33739437 doi102340 165019772814,1.0
cerebrospinal fluid analysis fam physician 2021 apr 1 103 7 422428abstractcerebrospinal fluid csf analysis diagnostic tool many conditions affecting central nervous system urgent indications lumbar puncture include suspected central nervous system infection subarachnoid hemorrhage csf analysis necessarily diagnostic can useful evaluation neurologic conditions spontaneous intracranial hypotension idiopathic intracranial hypertension multiple sclerosis guillainbarr syndrome malignancy bacterial meningitis high mortality rate characteristic effects csf white blood cell counts csf protein levels csfserum glucose ratio csf culture can identify causative organisms antibiotic sensitivities viral meningitis can present similarly bacterial meningitis usually low mortality rate adjunctive tests csf lactate measurement latex agglutination polymerase chain reaction testing can help differentiate bacterial viral causes meningitis immunocompromised patients may meningitis caused tuberculosis neurosyphilis fungal parasitic infections subarachnoid hemorrhage high mortality rate rapid diagnosis key improve outcomes computed tomography head nearly 100 sensitive subarachnoid hemorrhage first six hours symptom onset csf analysis may required delay presentation imaging findings equivocal xanthochromia elevated red blood cell count characteristic csf findings patients subarachnoid hemorrhage leptomeningeal carcinomatosis can mimic central nervous system infection poor prognosis largevolume csf cytology diagnosticpmid33788511,0.0
loss splicing factor ik impairs normal skeletal muscle development background ik splicing factor promotes spliceosome activation contributes premrna splicing although molecular mechanism ik previously reported vitro physiological role ik fully understood animal model generate ik knockout ko zebrafish using crispr cas9 system investigate physiological roles ik vivoresultsthe ik ko embryos display severe pleiotropic phenotypes implying essential role ik embryonic development vertebrates rnaseq analysis reveals downregulation genes involved skeletal muscle differentiation ik ko embryos exist genes improper premrna splicing among downregulated genes ik ko embryos display impaired neuromuscular junction nmj fasttwitch muscle development depletion ik reduces myod1 expression upregulates pax7a preventing normal fast muscle development noncellautonomous manner moreover differentiation induced ikdepleted c2c12 myoblasts myoblasts show reduced ability form myotubes however inhibition ik influence either muscle cell proliferation apoptosis zebrafish c2c12 cellsconclusionthis study provides splicing factor ik contributes normal skeletal muscle development vivo myogenic differentiation vitro,0.0
tactile cortical responses association tactile reactivity young children autism spectrum background unusual behavioral reactions sensory stimuli frequently reported individuals autism spectrum despite early emergence sensory features age 3 potential impact development quality life little known neural mechanisms underlying sensory reactivity early childhood autismmethodshere used electroencephalography eeg investigate tactile cortical processing young children aged 36 years autism neurotypical nt children scalp eeg recorded 33 children autism including low cognitive verbal abilities 45 age sexmatched nt children passive tactile fingertip stimulation compared properties early later somatosensoryevoked potentials seps adaptation repetitive stimulation autistic nt children assessed whether neural measures linked realworld parentreported tactile reactivityresultsas expected found elevated tactile reactivity children autism spectrum findings indicated differences amplitude latency early midlatency somatosensoryevoked potentials p50 n80 p100 adaptation autistic nt children however latency later processing tactile information n140 shorter young children autism compared nt children suggesting faster processing speed young autistic children correlational analyses exploratory analyses using tactile reactivity grouping variable found enhanced early neural responses associated greater tactile reactivity autismlimitationsthe relatively small sample size inclusion broad range autistic children eg low cognitive verbal abilities may limited power detect subtle group differences associations hence replications needed verify resultsconclusionsour findings suggest electrophysiological somatosensory cortex processing measures may indices realworld tactile reactivity early childhood autism together findings advance understanding neurophysiological mechanisms underlying tactile reactivity early childhood autism clinical context may therapeutic implications,0.0
role circadian clock cancer hallmark acquisition immunebased cancer therapeutics abstractthe circadian system temporally regulates physiology maintain homeostasis coopting disrupting circadian signals appear distinct attributes functionally important development tumor can enable give rise hallmarks tumors use facilitate initiation growth progression circadian signals also strong regulators immune cell proliferation trafficking exhaustion states play role tumors respond immunebased cancer therapeutics immunooncology heralded paradigm shift cancer therapeutics greater accuracy needed increase capability predicting will respond favorably likely experience troubling adverse effects immunotherapy insights circadian signals may refine understanding biological determinants response help answer fundamental question whether certain perturbations circadian signals interfere activity immune checkpoint inhibitors review body literature highlighting circadian disruption cancer promoter synthesize burgeoning evidence suggesting circadian signals play role tumors respond immunebased anticancer therapeutics goal develop framework advance understanding relationships circadian markers cancer biology immunotherapeutics bolstered new understanding relationships may pursued future clinical studies improve ability predict patients will respond favorably avoid adverse effects traditional immunebased cancer therapeutics,0.0
assessment comprehensibility industry conflicts interest disclosures multiple sclerosis researchers medical conferences jama netw open 2021 apr 1 4 4 e212167 doi 101001 jamanetworkopen20212167no abstractpmid33797555 doi101001 jamanetworkopen20212167,0.0
high efficacy onabotulinumtoxina treatment patients comorbid migraine depression metaanalysis background migraine depression highly prevalent partly overlapping disorders cause strong limitations daily life patients tend respond poorly therapies available diseases onabotulinumtoxina proven effective treatment migraine depression many studies addressed effect onabotulinumtoxina migraine depression separately growing body evidence suggests beneficial effects also patients comorbid migraine depression current metaanalysis systematically investigates extent onabotulinumtoxina efficient migraineurs depressionmethodsa systematic literature search performed based pubmed scopus web science earliest date till october 30 th 2020 mean standard deviation sd sample size used evaluate improvement depressive symptoms migraine using randomeffects empirical bayes modelresultsour search retrieved 259 studies eight met inclusion criteria onabotulinumtoxina injections administered patients chronic migraine major depressive disorder led mean reduction 894 points ci 1004 784 hbox p 001 bdi scale 590 points ci 992 188 hbox p 001 bdiii scale 619 points ci 952 286 hbox p 001 phq9 scale evaluating depressive symptoms case migrainerelated symptoms found mean reductions 410 ci 731 089 hbox p 001 points hit6 scale 3205 ci 5596 814 hbox p 001 midas scale 17 ci 327 013 hbox p 003 points vas scale 627 ci 848 407 hbox p 001 migraine episodes per month comorbid patients showed slightly better improvements bdi hit6 scores migraine frequency compared monomorbid patients latter group manifested better results midas vas scoresconclusiontreatment onabotulinumtoxina leads significant reduction disease severity chronic migraine major depressive disorder patients comorbid diseases comparative analyses suggest equivalent strong effect monomorbid comorbid patients beneficial effects specifically seen certain migraine features,0.0
exosomes derived human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis mir1925p il17ra smad axis background hypertrophic scar hs fibroproliferative disorder dermis burn trauma usually leads esthetic disfiguration functionary impairment patients emerging evidences demonstrated adscexo alleviate visceral fibrosis little attention paid role skin fibrosis study explore effect adscexo hs investigated exact mechanism underlying propertiesmethodsadscexo isolated identified internalized hsderived fibroblasts hsfs effect adscexo proliferation migration hsfs detected flow cytometry ki67 immunofluorescence staining scratch transwells assays respectively rtpcr immunoblotting immunofluorescence immunohistochemistry staining used evaluate expression il17ra col1 col3 sma sip1 psmad2 psmad3 hsfs stimulated adscexo mir1925p mimics inhibitors il17ra sirna negative controls digital morphology massons trichrome staining immunohistochemistry staining performed measure effect adscexo lvil17ra shrna excisional wound balb c miceresultsthe verified adscexo effectively inhibited proliferation migration hsfs decreased expression col1 col3 sma il17ra psmad2 psmad3 increased levels sip1 hsfs besides mice adscexotreated group demonstrated faster wound healing less collagen deposition furthermore mir1925p highly expressed adscexo adscexosomal mir1925p ameliorated hypertrophic scar fibrosis meanwhile mir1925p targeted expression il17ra decrease profibrotic proteins levels moreover il17ra overexpressed hs hsfs knockdown il17ra alleviated expression col1 col3 sma psmad2 psmad3 increased expression sip1 hsfs importantly il17ra silence also facilitated wound healing attenuated collagen production modulated smad pathway hsfsconclusionsthis study illustrated adscexo attenuated deposition collagen transdifferentiation fibroblaststomyofibroblasts formation hypertrophic scar vitro vivo experiments adscexosomal mir1925p targeted il17ra regulate smad pathway hypertrophic scar fibrosis adscexo promising therapeutic strategy clinical treatment hypertrophic scar antifibrotic properties achieved mir1925p il17ra smad axis,0.0
perimenopausal women show modulation excitatory inhibitory neuromuscular mechanisms background menopausal transition exposes women early decline muscle force motor function changes muscle quality function especially lower limbs crucial expose individuals increased risk falls elucidate related neuromuscular mechanisms investigated cortical inhibition peripheral muscle twitch force potentiation women early late stages perimenopausemethodsparticipants 63 women aged 4855 years categorized early ep n 25 late lp n 38 perimenopausal according serum folliclestimulating hormone fsh levels menstrual diaries ep women irregular menstrual cycle fsh 25 iu l lp women irregular cycle 25 iu l examined motor evoked potential mep silent period sp elicited transcranial magnetic stimulation tms tibialis anterior muscle 20 40 60 maximal voluntary contraction mvc levels twitch force potentiation plantar flexorsresultsep group showed longer sp duration 40 mvc condition larger motor evoked potential amplitude 20 mvc condition compared lp group group difference detected twitch force potentiation however correlated negatively fsh levels factors age height body mass index physical activity explain group differencesconclusionsour preliminary results indicate subtle modulation tmsinduced inhibitory excitatory mechanisms twitch force potentiation women already late perimenopausal stage suggests reduction estrogens may accelerating role aging process neuromuscular control,0.0
crosscultural adaptation validation finnish version central sensitization inventory relationship dizziness postural control background central sensitization cs involves dysfunction neurophysiological mechanisms increase neuronal responses noxious nonnoxious stimuli central nervous system central sensitization inventory csi considered leading patientreported outcome measure assessing csrelated symptoms aim study translate crossculturally adapt csi finnish csifi evaluate psychometric propertiesmethodstranslation crosscultural validation csi conducted according established guidelines validation sample 229 subjects including 42 pain free controls 187 subjects chronic musculoskeletal pain csifi evaluated internal consistency testretest reliability exploratory factor analysis maximum likelihood extraction relationship subjectreported outcome measures tampa scale kinesiophobia tsk depression scale deps 5level eq5d version eq5 l5d rolandmorris disability questionnaire rmdq pain sleep questionnaire threeitem index psq3 pain history subjective symptoms dizziness csrelated diagnoses csi part b furthermore studied ability csifi distinguish pain free controls subjects chronic pain single body area subjects multisite chronic pain addition studied relationship csifi scores postural control force plateresultsthe csifi demonstrated good internal consistency 0884 excellent testretest reliability 0933 7 1 day gap test administrations exploratory factor analysis maximum likelihood extraction yielded one factor solution fair good correlations found csifi tsk deps eq5 l5d rmdq psq3 subjective symptoms dizziness correlated better csifi scores csrelated diagnoses csi part b total csifi scores successfully distinguished pain free controls subjects chronic pain single body area subjects multisite chronic pain multisite pain group reported significantly dizziness symptoms two groups force plate measurements showed relationship postural control csifi scoresconclusionthe csifi translation successfully crossculturally adapted validated finnish csifi psychometric properties scores acceptable levels line previous csi validations csifi appears valid reliable instrument assessing csrelated symptomology finnishspeaking populations,0.0
klothodependent role 1 25 oh 2d3 brain neurosignals 2021 mar 31 29 1 1423 doi 1033594 000000352abstractthe antiaging protein klotho encoded klotho gene first identified aging suppressor mice klotho deficiency involved premature aging early death overexpression related longevity klotho mostly expressed kidney also brain organs two forms klotho cell membrane secreted form pleiotropic activities include regulation general metabolism oxidative stress mineral metabolism correlates effect accelerating aging membrane klotho serves obligate coreceptor fibroblast growth factor fgf secreted klotho plays role humoral factor klotho protein participates regulation several biological activities including regulation calciumphosphate homeostasis pth well vitamin d metabolism active form vitamin d 1 25 oh 2d3 1 25dihydroxyvitamin d3 calcitriol acts neurosteroid participates regulation multiple brain functions provides neuroprotection suppresses oxidative stress inhibits inflammation inflammatory mediators stimulates various neurotrophins calcitriol involved many brainrelated diseases including multiple sclerosis alzheimers disease parkinsons disease schizophrenia review covers recent advances klotho research discusses klothodependent roles calcitriol neuropsychopathophysiologypmid33784444 doi1033594 000000352,0.0
exercise rapidly alters proteomes mice following spinal cord demyelination sci rep 2021 mar 31 11 1 7239 doi 101038 s41598021865935abstractexercise affords broad benefits people multiple sclerosis pwms including less fatigue depression improved cognition animal models multiple sclerosis ms exercise shown improve remyelination decrease bloodbrain barrier permeability reduce leukocyte infiltration despite benefits many pwms refrain engaging physical activity barrier participation exercise may overcome uncovering describing mechanisms exercise promotes beneficial changes central nervous system cns show acute bouts exercise mice profoundly alters proteome demyelinating lesions following lysolecithin induced demyelination ventral spinal cord mice given immediate access running wheel 4 days lesioned spinal cords peripheral blood serum subjected tandem mass tag labeling shotgun proteomics workflow identify alteration protein levels identified 86 significantly upregulated 85 downregulated proteins lesioned spinal cord well 14 significantly upregulated 11 downregulated proteins serum following acute exercise altered pathways following exercise demyelinated mice include oxidative stress response metabolism transmission across chemical synapses similar acute bout exercise nave mice also changed several proteins serum spinal cord including metabolism antioxidant responses improving understanding mechanisms duration activity required influence injured cns motivate pwms conditions embrace exercise part therapy manage cns disabilitypmid33790323 doi101038 s41598021865935,1.0
experience using mtor inhibitors subependymal giant cell astrocytoma tuberous sclerosis complex single facility background subependymal giant cell astrocytoma sega occasionally seen tuberous sclerosis complex tsc two main options currently available treating sega surgical resection pharmacotherapy using mammalian target rapamycin inhibitors mtori hypothesized opportunities surgical resection sega reduced advent mtorimethodswe retrospectively reviewed charts patients treated august 1979 july 2020 divided premtori era group pregroup patients treated november 2012 postmtori era group postgroup comprising patients treated november 2012 mtori became available japan sega compared groups terms treatment surgery mtori also reviewed sega size rate acute hydrocephalus recurrence sega malignant transformation adverse effects mtoriresultsin total 120 patients tsc visited facility including 24 patients sega surgical resection significantly frequent pregroup 6 7 patients 86 postgroup 2 17 patients 12 p 0001 acute hydrocephalus seen 1 patient 4 patients showed malignant transformation sega group treated using mtori showed significantly smaller sega compared group treated waitandsee policy p 0012 adverse effects pharmacotherapy identified seven 64 6 oral ulcers 1 irregular menstruation 11 patients receiving mtoriconclusionsthe postgroup underwent surgery significantly less often pregroup since treatment option use mtori treatment sega tsc became available opportunities surgical resection decreased facility,0.0
ancaassociated vasculitis overlaps systemic sclerosis case report literature review background systemic sclerosis ssc antineutrophil cytoplasmic antibody anca associated vasculitis aav affect kidney may cause renal failure treatment aav dramatically different ssc renal crisis src kidney biopsy recommended diagnosing src reliable diagnostic method aavcase presentationhere 49yearold male patient diffuse ssc presented acute renal insufficiency detectable anca myeloperoxidasespecific antibodies renal biopsy revealed necrotizing glomerulonephritis consistent aav finding confirms existence aav ssc overlap syndrome patient treated intravenous methylprednisolone intravenous cyclophosphamide tandem membrane plasma exchange hemodialysis treatment clinical symptoms remained stable creatinine creactive protein crp levels remained normalized recent followup hospital dischargeconclusionsaav can overlap ssc although condition rare associated considerable morbidity mortality therefore critical recognize aav setting worsening renal function due sss provide appropriate treatment several clinical features suggestive aav rather src renal biopsy required accurate diagnosis,0.0
autoantibodies speckled protein family primary biliary cholangitis abstractthe autoantibody profile primary biliary cholangitis pbc includes antinuclear antibodies ana detectable indirect immunofluorescence 50 pbc patients one two immunofluorescence patterns historically considered pbcspecific socalled multiple nuclear dots mnd targeting nuclear body proteins sp100 sp140 sp140l proteins promyelocytic leukemia protein pml small ubiquitinrelated modifier proteins sumo hypothesized role nuclear body protein alterations immune disorders pbc thus suggesting novel refined therapeutic approaches,0.0
upf1 reduces c9orf72 hreinduced neurotoxicity absence nonsensemediated decay dysfunction cell rep 2021 mar 30 34 13 108925 doi 101016 jcelrep2021108925abstractmultiple cellular pathways suggested altered c9orf72 ggggcc g4c2 hexanucleotide repeat expansion hre including aspects rna regulation nonsensemediated decay nmd investigate role overexpression upf1 protein involved nmd plays mitigating neurotoxicity multiple models c9orf72 als ftd first show nmd altered endogenous induced pluripotent stem cell ipsc derived spinal neuron ipsn model c9orf72 als c9als postmortem motor cortex tissue c9als patients unexpectedly find upf1 overexpression significantly reduces severity known neurodegenerative phenotypes without altering nmd function upf1 overexpression reduces poly gp abundance without altering amount repeat rna providing potential mechanism upf1 reduces dipeptide repeat dpr proteinmediated toxicity together findings indicate upf1 neuroprotective context c9als albeit independent known upf1mediated nmd pathwayspmid33789100 doi101016 jcelrep2021108925,1.0
nlrp3 inflammasome emerging therapeutic target chronic pain abstractchronic pain affects life quality suffering patients posts heavy problems health care system conventional medications usually insufficient chronic pain management oftentimes results many adverse effects nlrp3 inflammasome controls processing proinflammatory cytokine interleukin 1 il1 implicated variety disease conditions recently growing number evidence suggests nlrp3 inflammasome dysregulated chronic pain condition contributes pathogenesis chronic pain review provides uptodate summary recent findings involvement nlrp3 inflammasome chronic pain discussed expression regulation nlrp3 inflammasomerelated signaling components chronic pain conditions review also summarized successful therapeutic approaches target nlrp3 inflammasome chronic pain treatment,0.0
cuprizone eae mouse frontal cortex proteomics revealed proteins altered multiple sclerosis sci rep 2021 mar 30 11 1 7174 doi 101038 s41598021861915abstracttwo pathophysiological different experimental models multiple sclerosis analyzed parallel using quantitative proteomics attempts discover protein alterations applicable diagnostic prognostic treatment targets human disease cuprizone model reflects de remyelination multiple sclerosis experimental autoimmune encephalomyelitis eae mog1125 immunemediated events frontal cortex peripheral severely inflicted areas cns dissected analyzed frontal cortex previously characterized proteomics different disease stages novel protein alterations involved protecting healthy tissue assisting repair inflicted areas might discovered using tmtlabelling mass spectrometry 1871 proteins quantified overlapped two experimental models fold change compared controls verified using labelfree proteomics similarities frontal cortex two disease models observed regulated proteins signaling pathways compared legumain c1q complement proteins among upregulated proteins cuprizone hemopexin eae model immunohistochemistry showed legumain expression postmortem multiple sclerosis brain tissue n 19 significantly higher center edge white matter active chronic active lesions legumain associated increased lesion activity might valuable drug target using specific inhibitors already suggested parkinsons alzheimers disease cerebrospinal fluid levels legumain c1q hemopexin significantly different multiple sclerosis patients neurological diseases healthy controlspmid33785790 doi101038 s41598021861915,1.0
tuberous sclerosis complex critical role interventional radiologist management sa j radiol 2021 mar 30 25 1 2034 doi 104102 sajrv25i12034 ecollection 2021abstracttuberous sclerosis complex tsc autosomal dominant neurocutaneous syndrome characterised hamartomas multiple organs characteristic imaging features illustrated case report angiomyolipoma aml common renal manifestation tsc may present lifethreatening haemorrhage time diagnosis interventional management selective renal embolisation currently treatment choice safe effective management ruptured renal amlpmid33936797 pmcpmc8063773 doi104102 sajrv25i12034,0.0
cerebrospinal fluid findings patients psychotic symptomsa retrospective analysis sci rep 2021 mar 30 11 1 7169 doi 101038 s4159802186170wabstractin current international classification systems icd10 dsm5 diagnostic criteria psychotic disorders eg schizophrenia schizoaffective disorder based symptomatic descriptions since unambiguous biomarkers known date however underlying causes psychotic symptoms like inflammation ischemia tumor affecting neural tissue can identified different classification used psychotic disorder delusions due known physiological condition icd10 f062 psychosis caused medical factors dsm5 csf analysis still considered optional current diagnostic guidelines psychotic disorders csf biomarkers help identify known physiological conditions retrospective partly descriptive analysis 144 patients psychotic symptoms available csf data analyzed csf examinations significance differentiate patients specific etiological factors f062 patients schizophrenia schizotypal delusional nonmood psychotic disorders f2 403 patients least one csf parameter reference range abnormal csffindings found significantly often patients diagnosed f062 882 compared patients diagnosed f2 238 p 000001 total 17 cases identified probably caused specific etiological factors f062 ten cases fulfilled criteria probable autoimmune psychosis linked following autoantibodies amphiphysin caspr2 cv2 lgl1 nmda zic4 titin two cases presented antithyroid tissue autoantibodies four cases probable causal factors identified covid19 frontal intracranial tumor multiple sclerosis n 2 neurosyphilis twentyone cases remained reliable diagnostic classification age onset psychotic symptoms differed patients diagnosed f2 f062 p 0014 latter group older median 44 vs 28 years various csf parameters analyzed exploratory analysis identifying pleocytosis oligoclonal bands ocbs discriminators f062 vs f2 high specificity 96 group differences found gender characteristics psychotic symptoms substance dependency family history study emphasizes great importance detailed diagnostic workup diagnosing psychotic disorders including csf analysis detect possible underlying pathologies improve treatment decisionspmid33785807 doi101038 s4159802186170w,0.0
cognitive issues pediatric multiple sclerosis brain sci 2021 mar 30 11 4 442 doi 103390 brainsci11040442abstractmultiple sclerosis ms one leading causes disability young adults onset ms developmental age makes pediatric patients particularly susceptible cognitive impairment resulting diseaserelated damage failure ageexpected brain growth despite different test batteries definitions cognitive impairment consistently reported approximately onethird pediatric patients ms however lack uniform definition cognitive impairment adoption different test batteries led divergent results terms cognitive domains frequently affected across cohorts explored heterogeneity hampered large international collaborative studies moreover research aimed identification risk factors eg demographic clinical radiological features protective factors eg cognitive reserve leisure activities cognitive decline still scanty mood disorders depression anxiety can detected patients alongside cognitive decline isolation can negatively affect quality life scores well academic performances using mri cognitive impairment attributed damage specific brain compartments well abnormal network activation patterns however multimodal mri studies still needed order assess contribution mri metric cognitive impairment importantly longitudinal studies recently demonstrated failure ageexpected brain growth white matter wm gray matter gm maturation plays relevant role determining cognitive dysfunction addition msrelated direct damage whether growth retardations might result specific cognitive profiles according age disease onset studied yet better characterization cognitive profiles pediatric ms patients well definition neuroanatomical substrates cognitive impairment longitudinal evolution needed develop efficient therapeutic strategies cognitive impairment patient populationpmid33808278 doi103390 brainsci11040442,0.0
uncommon radiologic computed tomography appearances chest patients lymphangioleiomyomatosis sci rep 2021 mar 30 11 1 7170 doi 101038 s41598021859995abstractlymphangioleiomyomatosis lam rare destructive lung disease characterized multiple thinwalled pulmonary cysts currently proposed diagnostic algorithm emphasizes characteristic cystic appearance highresolution computed tomography hrct uncommon hrct appearances present challenges establishing proper lam diagnosis objective study accrue uncommon chest hrct appearances determine frequencies tuberous sclerosis complex tsc associated lam tsclam sporadic lam slam patients 311 females referred hospital including 272 slam patients mean age 392 years 39 tsclam patients mean age 383 years retrospectively evaluated found 2 types radiologic findings likely make hrct cyst appearance atypical characteristics cyst uncommon findings addition cysts found approximately 80 lam patients whether tscassociated sporadic showed typical hrct appearance mild severe cystic destruction remaining 20 displayed unusual profiles cyst appearance well additional findings aside cyst former includes large cyst thickened walls irregularly shaped whereas latter includes ground glass attenuation diffuse noncalcified nodules important aware various radiologic findings make hrct cystic appearance atypical lampmid33785773 doi101038 s41598021859995,0.0
cerebrospinal fluid biomarkers myeloid glial cell activation correlated multiple sclerosis lesional inflammatory activity front neurosci 2021 mar 30 15649876 doi 103389 fnins2021649876 ecollection 2021abstractmultiple sclerosis ms related inflammation can divided lesional activity mediated immune cells migrating periphery central nervous system cns nonlesional activity mediated inflammation compartmentalized cns tissue lesional inflammatory activity reflected contrastenhancing lesions cels magnetic resonance imaging mri effectively inhibited current disease modifying therapies dmts effect dmts nonlesional inflammatory activity currently unknown reliable simultaneous measurements lesional nonlesional ms activity necessary understand contribution cns tissue destruction individual patients previously demonstrated cns compartmentalized inflammation can measured combined quantification cerebrospinal fluid csf immune cells cellspecific soluble markers goal study develop validate csfbiomarkerbased molecular surrogate ms lesional activity training cohort dichotomized active cels 1 clinical relapse inactive lesional activity cels relapse groups matched csf serum samples analyzed 20 inflammatory axonal damage biomarkers blinded fashion findings training cohort less 01 probability false positive ie p 0001 validated independent validation cohort ms patients lesional activity elevated il12p40 chi3l1 tnf tnf il10 first two strongest effects validated statisticallysignificant association lesional activity independent validation cohort marker axonal damage neurofilament light nfl measured csf cnfl also significantly elevated ms patients active lesions nfl measured serum snfl differentiate two ms subgroups predetermined significance p 00690 even though ccsf snfl correlated rho 066 p 00001 finally additive model il12p40 chi3l1 outperforms biomarker discretely il12p40 chi3l1 released predominantly immune cells myeloid lineage reproducibly best csf biomarkers ms lesional activity residuals il12p40 chi3l1cnfl correlations may identify ms patients destructive inflammation contributing neurodegenerationpmid33859547 pmcpmc8042223 doi103389 fnins2021649876,0.0
vitamin d epsteinbarr virus endogenous retroviruses multiple sclerosis facts hypotheses j integr neurosci 2021 mar 30 20 1 233238 doi 1031083 jjin202101392abstractthe pathogenesis multiple sclerosis ms remains poorly understood presumably ms caused multiple environmental epigenetic genetic factors among human endogenous retroviruses hervs epsteinbarr virus ebv vitamin d suggested play role pathogenesis course ms vitamin d can affect immune system infections can hypothesized close interplay vitamins ebv erv pathogenesis ms summarize important data vitamin d including polymorphisms genes related vitamin d metabolism ebv erv pathogenesis ms create hypotheses regarding interactions data indicate vitamin d strong impact viral infections interferes ebv infection ebv capable activating silent ervs believe ebv missing link vitamin d erv ms pathogenesispmid33834708 doi1031083 jjin202101392,0.0
neurological manifestations complications coronavirus disease 2019 covid19 systematic review metaanalysis background spectrum neurological involvement covid19 thoroughly understood best knowledge systematic review metaanalysis subgroup comparison severe nonsevere cases published aim study assess frequency neurological manifestations complications identify neurodiagnostic findings compare aspects severe nonsevere covid19 casesmethodsa systematic search pubmed scopus ebsco web science google scholar databases conducted studies published 1st january 2020 22nd april 2020 addition scanned bibliography included studies identify potentially eligible studies criteria eligibility included studies published english language translated english involving patients covid19 age groups reporting neurological findings data extracted eligible studies metaanalyses conducted using comprehensive metaanalysis software randomeffects model used calculate pooled percentages means 95 confidence intervals cis sensitivity analysis performed assess effect individual studies summary estimate subgroup analysis conducted according severity main outcomes study identify frequency nature neurological manifestations complications neurodiagnostic findings covid19 patientsresults44 articles included pooled sample size 13 480 patients mean age 503 years 53 males common neurological manifestations myalgia 222 95 ci 172 281 taste impairment 196 95 ci 38 601 smell impairment 183 95 ci 154 762 headache 121 95 ci 91 158 dizziness 113 95 ci 85 150 encephalopathy 94 95 ci 28 266 nearly 25 95 ci 1 61 patients acute cerebrovascular diseases cvd myalgia elevated ck ldh acute cvd significantly common severe cases moreover 20 case reports assessed qualitatively data presented separatelyconclusionsneurological involvement common covid19 patients early recognition vigilance involvement might impact overall outcomes,0.0
tissuerestricted control established central nervous system autoimmunity tnf receptor 2expressing treg cells proc natl acad sci u s 2021 mar 30 118 13 e2014043118 doi 101073 pnas2014043118abstractcd4+foxp3+ regulatory t treg cells central modulators autoimmune diseases however timing location treg cellmediated suppression tissuespecific autoimmunity remain undefined addressed questions investigating role tumor necrosis factor tnf receptor 2 tnfr2 signaling treg cells experimental autoimmune encephalomyelitis eae model multiple sclerosis found tnfr2expressing treg cells critical suppress eae peak disease central nervous system impact t cell priming lymphoid tissues disease onset mechanistically tnfr2 signaling maintained functional treg cells sustained expression ctla4 blimp1 allowing active suppression pathogenic t cells inflamed central nervous system late effect treg cells confirmed treating mice tnf tnfr2 agonists antagonists findings show endogenous treg cells specifically suppress autoimmune disease acting target tissue overt inflammation moreover bring mechanistic insight adverse effects antitnf therapy patientspmid33766913 doi101073 pnas2014043118,0.0
viscoelastic properties white gray matterderived microglia differentiate upon treatment lipopolysaccharide upon treatment myelin background biomechanical properties brain increasingly shown relate brain pathology neurological diseases including multiple sclerosis ms inflammation demyelination ms induce significant changes brain stiffness can linked relative abundance glial cells lesions hypothesize biomechanical addition biochemical properties white wm gray matter gm derived microglia may contribute differential microglial phenotypes seen ms wm gm lesionsmethodsprimary glial cultures wm gm rat adult brains treated either lipopolysaccharide lps myelin myelin+lps 24 h left untreated control treatment microglial cells indented using dynamic indentation determine storage loss moduli reflecting cell elasticity cell viscosity respectively subsequently fixed immunocytochemical analysis parallel gene expression inflammatoryrelated genes measured using semiquantitative rtpcr finally phagocytosis myelin determined well factin visualized study cytoskeletal changesresultswmderived microglia significantly elastic viscous microglia derived gm heterogeneity microglia biomechanical properties also apparent treated lps wmderived microglia decreased cell elasticity viscosity gmderived microglia increased elasticity viscosity increase elasticity viscosity observed gmderived microglia accompanied increase tnf mrna reorganization factin absent wmderived microglia contrast treated myelin wm gmderived microglia phagocytose myelin decrease elasticity viscosityconclusionsin demyelinating conditions myelin debris phagocytized ms lesions likely observed differences wm versus gmderived microglia biomechanics mainly due difference response inflammation rather event demyelination thus differential biomechanical properties wm gm microglia may add differential biochemical properties depend inflammation present wm gm lesions ms patients,1.0
role picornavirus infection epileptogenesis abstractpicornaviridae family small positivestrand rna viruses transmitted via respiratory fecaloral route neurotropic picornaviruses can induce acute late recurrent seizures following central nervous system infection infecting peripheral nerve crossing bloodbrain barrier migrating trojanhorse method theilers murine encephalomyelitis virus tmev member picornaviridae family can cause encephalitis leading chronic spontaneous seizures tmevinfected c57bl 6 mice used animal model exploring mechanism epileptogenesis assessing new antiepileptic drugs astrogliosis neuronal death microglial recruitment detected hippocampus following picornaviruseinduced encephalitis macrophages monocytes neutrophils well il6 tnf released play important role epileptogenesis review summarize clinical characteristics picornavirus infection immunopathology involved tmevinduced epilepsy,0.0
destination amyotrophic lateral sclerosis front neurol 2021 mar 29 12596006 doi 103389 fneur2021596006 ecollection 2021abstractamyotrophic lateral sclerosis als prototypical neurodegenerative disease characterized progressive degeneration motor neurons brain spinal cord constantly evolving nature als represents fundamental dimension individual differences underlie disorder yet involves multiple levels functional entities alternate different directions finally converge functionally define als disease progression als may start single entity gradually becomes multifactorial however functional convergence diverse entities eventually defining als progression poorly understood various hypotheses proposed without consensus forandagainst schools thought present review aims capture explanatory hierarchy terms hypotheses mechanisms provide better insights functionally connect can integrate within common functional frame reference better understanding als defining future treatments possible therapeutic strategies provide philosophical understanding early leads crucial understanding endpoints als invariably early symptomatic leads underpinned neurodegeneration cellular molecular genomic levels consolidation ideas applied neurodegenerative diseases nds guide critical thinking unveil roadmap destination alspmid33854469 pmcpmc8039771 doi103389 fneur2021596006,0.0
compensatory image stability people multiple sclerosis atrial vertigo based posturography examination sci rep 2021 mar 29 11 1 7027 doi 101038 s4159802185983zabstractpathophysiology balance disorders due multiple sclerosis ms atrial vertigo av different evaluated posture stability maintaining balance people ms presenting symptoms ataxia av included 45 women 15 ms 15 av 15 controls posturography platform used measure balance parameters characterize image stability compensation balance disorders surface area stabilogram sas vision control index vci visionmotion control index vmci used stability image people ms av eyes open p 0002 eyes closed p 0080 visual biofeedback p 00008 differed significantly sas depended visual biofeedback regardless occurrence balance disorders basis determining compensatory share visionmotor coordination differences vci groups insignificant vmci significantly higher people balance disorders without similar ms av groups image stability different people ms av thanks visual biofeedback becomes possible launch effective visionmotor coordination compensating balance disorders vci may become measure compensation balance disorderspmid33782416 doi101038 s4159802185983z,0.0
data sharing goals nonprofit funders clinical trials j particip med 2021 mar 29 13 1 e23011 doi 102196 23011abstractsharing clinical trial data can provide value research participants communities accelerating development new knowledge therapies investigators merge data sets conduct new analyses reproduce published findings raise standards original research learn work others generate new research questions nonprofit funders including disease advocacy patientfocused organizations play pivotal role promotion implementation data sharing policies funders uniquely positioned promote support culture data sharing serving trusted liaisons potential research participants investigators wish access participants networks clinical trial recruitment short nonprofit funders can drive policies influence research culture purpose paper detail set aspirational goals forward thinking collaborative data sharing solutions nonprofit funders fold existing funding policies goals paper convey complexity opportunities challenges facing nonprofit funders appropriate prioritization data sharing within organizations may serve starting point data sharing toolkit nonprofit funders clinical trials provide clarity mission mechanisms enforce data sharing practices communities already expect happeningpmid33779573 doi102196 23011,0.0
metformin ameliorates severity experimental alport syndrome sci rep 2021 mar 29 11 1 7053 doi 101038 s41598021861091abstractmetformin widely used treatment type 2 diabetes increasing numbers studies shown metformin also ameliorates tumor progression inflammatory disease fibrosis however ability metformin improve nondiabetic glomerular disease chronic kidney disease ckd explored investigate effect metformin nondiabetic glomerular disease used mouse model alport syndrome col4a5 g5x treated metformin losartan used control treatment also investigated effect metformin adriamycininduced glomerulosclerosis model pathological biochemical analysis showed metformin losartan suppressed proteinuria renal inflammation fibrosis glomerular injury extended lifespan alport syndrome mice transcriptome analysis showed metformin losartan influenced molecular pathwaysrelated metabolism inflammation metformin altered multiple genes including metabolic genes affected losartan metformin also suppressed proteinuria glomerular injury adriamycininduced glomerulosclerosis mouse model results showed metformin ameliorates glomerular sclerosis ckd phenotype nondiabetic chronic glomerular diseases metformin may therapeutic potential diabetic nephropathy also nondiabetic glomerular disease including alport syndromepmid33782421 doi101038 s41598021861091,0.0
systematic review exploring bidirectional relationship puberty autoimmune rheumatic diseases background autoimmune rheumatic diseases ards associated significant sexbias becomes evident postpuberty systematic review aims elucidate bidirectional relationship puberty ardrelated outcomesmethodsstudies published english october 2019 identified using systematic search endocrinology rheumatology literature information extracted study design sample size demographics puberty outcome measures disease outcome measures main findings methodological quality studies included analysed using newcastleottawa scale nos resultssixteen nonrandomised studies reporting impact puberty ard outcomes n 7 ard impact pubertyrelated outcomes n 8 n 1 identified impact puberty ard outcomes investigated patients juvenile idiopathic arthritis jia associated uveitis n 1 juvenile systemic lupus erythematosus jsle n 5 healthy controls developed adultonset sle n 1 nonspecific symptoms n 1 impact ard puberty outcomes explored jia n 4 jsle n 3 quality assessment studies showed small moderate risk bias overall nos 49 9 due large heterogeneity studies possible perform metaanalysis multiple studies reported delayed puberty patients jia jsle menstrual hormonal abnormalities lower height weight controls earlier prepubertal onset jsle correlated severe disease need systemic treatmentconclusiona bidirectional relationship exists puberty ards however better research required elucidate complexity relationship propose pubertyrelated clinical assessments patients ards can improve patient outcomes facilitate future research,0.0
prevalence factors related urinary incontinence older adults women worldwide comprehensive systematic review metaanalysis observational studies background urinary incontinence common condition general population particular older adults population reduces quality life people study aims systematically examine metaanalyse overall prevalence urinary incontinence older women around world related influential factorsmethodsthis report comprehensive systematic review metaanalysis findings research urinary incontinence older adults people across world looking medline cochrane library sciencedirect embase scopus proquest persian databases namely iranmedex magiran sid january 2000 april 2020 heterogeneity experiments measured using i2 index data processing done systematic metaanalysis programmeresultsin 29 studies sample size 518 465 people age range 55106 years urinary incontinence older adults women world based metaanalysis 371 95 ci 296454 obtained highest prevalence urinary incontinence reported older adults women asia 451 95 ci 369535 metaregression also showed increasing sample size year study overall prevalence urinary incontinence older adults women world decreased increased respectively statistically significant differences p 005 according studies important factors influencing incidence urinary incontinence older women womens age p 0001 obesity p 0001 diabetes p 0001 womens education p 0001 delivery rank p 0001 hypertension p 0001 smoking p 0001 also urinary tract infections p 0001 conclusiongiven high prevalence urinary incontinence older women around world health policy makers must consider control diagnostic measures older women prioritize treatment rehabilitation activities,0.0
exercise diminishes plasma neurofilament light chain reroutes kynurenine pathway multiple sclerosis neurol neuroimmunol neuroinflamm 2021 mar 29 8 3 e982 doi 101212 nxi0000000000000982 print 2021 mayabstractobjective examine acute singlebout training effects highintensity interval training hiit vs standard exercise therapy moderate continuous training mct plasma neurofilament light chain pnfl kynurenine kyn pathway tryptophan degradation metabolites persons multiple sclerosis pwms methods sixtynine pwms expanded disability status scale score 3060 randomly assigned hiit mct group changes pnfl kyn pathway metabolites measured blood plasma assessed 3 hours first training session well 3week training interventionresults acute exercise reduced pnfl increased kyn pathway flux toward neuroprotective kynurenic acid ka changes pnfl correlated positively changes ka negatively quinolinic acidtoka ratio hiit consistently led greater effects mct following 3week training intervention kyn pathway activated hiit compared mctconclusion future studies clinical assessments pnfl consider acute exercise confounding factor measurement reliability moreover exerciseinduced kyn pathway rerouting might mediate neuroprotection potentially underlying benefits rehabilitation pwmsclassification evidence study provides class ii evidence acute hiit diminishes pnfl increases ka levels 3 weeks hiit activate kyn pathway pwmstrial registration information clinical trial registration number nct03652519pmid33782190 doi101212 nxi0000000000000982,1.0
emerging therapeutics immune tolerance tolerogenic vaccines t cell therapy il2 therapy front immunol 2021 mar 29 12657768 doi 103389 fimmu2021657768 ecollection 2021abstractautoimmune diseases affect roughly 510 total population women affected men standard treatment autoimmune autoinflammatory diseases long immunosuppressive agents advent immunomodulatory biologic drugs aimed blocking inflammatory mediators including proinflammatory cytokines frontier biologic drugs tnf blockers therapies inhibit proinflammatory action tnf common autoimmune diseases rheumatoid arthritis psoriasis ulcerative colitis crohns disease tnf blockade quickly became standard care autoimmune diseases due effectiveness controlling disease decreasing patients adverse risk profiles compared broadspectrum immunosuppressive agents however antitnf therapies limitations including known adverse safety risk loss therapeutic efficacy due drug resistance lack efficacy numerous autoimmune diseases including multiple sclerosis next wave truly transformative therapeutics aspire provide cure selectively suppressing pathogenic autoantigenspecific immune responses leaving rest immune system intact control infectious diseases malignancies review will focus three main areas active research immune tolerance first tolerogenic vaccines aiming robust lasting autoantigenspecific immune tolerance second t cell therapies using tregs either polyclonal antigenspecific genetically engineered express chimeric antigen receptors establish active dominant immune tolerance t cells engineered express chimeric antigen receptors delete pathogenic immune cells third il2 therapies aiming expanding immunosuppressive regulatory t cells vivopmid33854514 pmcpmc8039385 doi103389 fimmu2021657768,0.0
feature cognitive dysfunction patients temporal lobe epilepsy clinical influencing factors zhong nan da xue xue bao yi xue ban 2021 mar 28 46 3 240248 doi 1011817 jissn167273472021200770abstractobjectives comprehensively analyze characteristics cognitive impairment temporal lobe epilepsy tle explore effects different lateral patients cognitive impairment different clinical factors cognitive impairment tlemethods total 84 patients met diagnostic criteria tle department neurology xiangya hospital collected patient group 36 cases left tle 48 cases right tle total 79 healthy volunteers matching gender age education level selected control group minimental state examination mmse montreal cognitive assessment moca scores arithmetic test information test digit symbol substitution test dsst block design test bdt hayling test verbal fluency test vft revised chinese adult wechsler intelligence scale retrospectively analyzed 2 groupsmultiple regression analysis used analyze relationship clinical factors cognitive impairment scoreresults compared control group tle patient group low scores neuropsychological tests significant difference p005 compared control group significant difference different neuropsychological tests patients tle different sides p005 left tle low scores information test arithmetic vft completion time hayling test part completion time hayling test part b correct number hayling test part correct number hayling test part b bdt forward digit span test fdst backward digit span test bdst right tle low scores information test arithmetic dsst vft completion time hayling test part correct number hayling test part completion time hayling test part b correct number hayling test part b bdt fdst bdstconclusions multiple cognitive domain dysfunctions tle including language shortterm memory longterm memory attention working memory executive function visual space function left tle greater impairment executive function right tle greater damage working memory long pathography disease hippocampal sclerosis history febrile convulsions may lead severe cognitive impairment earlier identification earlier intervention needed improve prognosis patientspmid33927070 doi1011817 jissn167273472021200770,0.0
review hematopoietic stem cell transplantation autoimmune diseases multiple sclerosis systemic sclerosis crohn#39 s disease position paper brazilian society bone marrow transplantation autoimmune diseases important field development bone marrow transplantation hematopoietic stem cell transplantation europe alone almost 3000 procedures registered far brazilian society bone marrow transplantation sociedade brasileira de transplantes de medula ossea organized consensus meetings autoimmune diseases group review available literature hematopoietic stem cell transplantation autoimmune diseases aiming gather data support procedure patients three autoimmune diseases evidencebased indications hematopoietic stem cell transplantation multiple sclerosis systemic sclerosis crohns disease professional stem cell transplant societies america europe brazil sociedade brasileira de transplantes de medula ossea currently consider hematopoietic stem cell transplantation therapeutic modality three autoimmune diseases article reviews evidence available,0.0
opg rankl rank gene methylation among alcoholinduced femoral head necrosis northern chinese men background purposealcoholinduced osteonecrosis femoral head onfh complex heterogeneous disease genetic factors epigenetic modifications one pathogenesis disease however influence epigenetic factors disease systematically studied research aims determine methylation changes alcoholinduced onfhmethodsan analytical crosssectional study chinese male population 50 alcoholinduced onfh patients 50 controls epityper sequenom massarray platform used detect dna methylation status 132 cytosinephosphateguanine cpg sites opg rankl rank gene promoter regionresultsin whole study group chisquare test used analyze methylation rate two groups six cpg sites found different among opg1_cpg_2 opg3_cpg_4 rank1_cpg_6 rank3_cpg_10 rankl2_cpg_21 rankl2_cpg_46 case group higher control group opg4_cpg_2 lower control group results showed patients alcoholinduced onfh 146 cpg sites examined differences methylation levels compared healthy controls 32 detected 23 remaining 114 sites showed differences methylation levels compared alcoholinduced onfh patients receiver operator characteristic roc curve analysis demonstrated methylation levels opg rankl rank efficiently predict existence alcoholinduced onfhconclusionour study chinese men suggests several cpg sites opg rankl rank gene peripheral blood leukocytes patients alcoholinduced onfh abnormal methylation state hypermethylation tended frequent,0.0
urinary sodiumtopotassium ratio associates hypertension current disease activity patients rheumatoid arthritis crosssectional study background excessive salt intake thought exacerbate development hypertension autoimmune diseases animal models clinical impact excessive salt rheumatoid arthritis ra patients still unknown performed crosssectional study clarify associations salt load index urinary sodiumtopotassium ratio na k ratio current disease activity hypertension ra populationmethodsthree hundred thirtysix participants cohort database kurama enrolled used spot urine na k ratio simplified index salt loading used 28joint ra disease activity score das28esr indicator current ra disease activity using indicators evaluated statistical associations urinary na k ratio das28esr prevalence hypertensionresultsurinary na k ratio positively associated measured systolic diastolic blood pressure also prevalence hypertension even covariate adjustment 134 p 0001 addition increased urinary na k ratio significantly positively correlated das28esr multiple regression analysis estimate 012 p 0001 also case genderseparated prednisoloneseparated subanalysesconclusionurinary na k ratio independently associated current disease activity well prevalence hypertension ra patients thus dietary modifications salt restriction potassium supplementation investigated potential candidate attenuating disease activity hypertension ra patients,0.0
increasing spectrum white matter diseases tigroid pattern mri glutaric aciduria type 1 case report background white matter diseases present magnetic resonance imaging focal diffuse t2hyperintensities however radially oriented stripes low relatively normal signal intensity observed within diffusely affected t2hyperintense cerebral white matter called tigroid pattern literature fornix tiny white matter fibers bundle playing crucial role cognitive functioning easily overlooked magnetic resonance imaging described inborn errors metabolismcase presentationwe present case glutaric aciduria type 1 followup nine years course disease presented three magnetic resonance scans age 8 21 months 10 years diffusion restriction fornix scan 1 2 tigroid pattern scan 3 despite appropriate diet supplementation injury white matter progressed achieving diffuse stage tigroid pattern psychological tests revealed deficits patients specific cognitive skills likely related damage fornixconclusionsto knowledge first report tigroid pattern white matter involvement glutaric aciduria type 1 first report forniceal injury disease seems correlated patients low functioning kinds memory skills previously reported glutaric aciduria type 1,0.0
sexual dysfunction men multiple sclerosis read interest review dastoorpoor colleagues 1 highlighting prevalence sexual dysfunction men multiple sclerosis ms congratulate authors bringing together research important topic high prevalence sexual dysfunction may caused least part high prevalence psychological symptoms ms may also precipitate compound existing psychological symptoms impact quality lifewe like highlight importance contrasting work related prevalence sexual dysfunction ms broader community samples considering research given sexual dysfunction men prevalent increases age common ageingrelated comorbidities eg diabetes cardiovascular disease 2 example one review highlighted sexual dysfunction occurs 52 men community positive relationship increasing age 3 turkishbased internet survey reported 433 male respondents experienced sexual dysfunction 72 5560yearold range 4 authors point research sexual dysfunction men ms shown incidence increase age shown community samples discussion prevalence sexual dysfunction broadly distinguish msspecific sexual dysfunction compared dysfunction related comorbidities ageingrelated processes warrantedwhile systematic review metaanalysis limited available data original studies believe need consider sexual dysfunction across spectrum severity mild severe current review aptly pointed differences measurement tools used across studies discussion measurement severity impact prevalence estimates warranted danish community study found 11 male respondents reported sexual dysfunction frequent perceived problem 68 males reported less severe sexual difficulties 5 many studies included review dastoorpoor colleagues 1 reported severity enabling qualitative synthesis discussion primary secondary tertiary causal aspects sexual dysfunction also reported many included studies providing opportunity nuanced discussion causal impact attributable ms disease processes symptoms ms comorbid factors given effort goes data search screening systematic review encourage authors maximise scientific value work secondary extraction data synthesis report aspectswe wish thank authors bringing research together summarising information prevalence sexual dysfunction men ms date hope encouraged followup article detailing aspects future reviews topic will considered perspective sexual dysfunction men broadly across severity dysfunction potential causal aspects contextualise knowledge area detailed understanding important clinical issue assist appropriate clinical attention management well referral support maximise quality life men ms experience sexual dysfunction,0.0
disability outcomes nmomentum trial inebilizumab neuromyelitis optica spectrum disorder neurol neuroimmunol neuroinflamm 2021 mar 26 8 3 e978 doi 101212 nxi0000000000000978 print 2021 mayabstractobjective assess treatment effects expanded disability status scale edss score worsening modified rankin scale mrs scores nmomentum trial inebilizumab humanized anticd19 monoclonal antibody participants neuromyelitis optica spectrum disorder nmosd methods adults n 230 aquaporin4 immunoglobulin gseropositive nmosd seronegative neuromyelitis optica edss score 8 randomized 31 receive inebilizumab 300 mg placebo days 1 15 randomized controlled period rcp 28 weeks adjudicated attack option enter inebilizumab openlabel period threemonth edssconfirmed disability progression cdp assessed using cox proportional hazard model effect baseline subgroups disability assessed interaction tests mrs scores rcp analyzed wilcoxonmannwhitney odds approachresults compared placebo inebilizumab reduced risk 3month cdp hazard ratio hr 0375 95 ci 01480952 p 00390 baseline disability prestudy attack frequency disease duration affect treatment effect observed inebilizumab hrs 02130503 interaction tests p 005 indicating effect baseline covariates outcome mean edss scores improved longerterm treatment inebilizumabtreated participants likely favorable mrs outcome end rcp 1663 95 ci 11952385 p 00023 conclusions disability outcomes favorable inebilizumab vs placebo participants nmosdclassification evidence study provides class ii evidence patients nmosd inebilizumab reduces risk worsening disability nmomentum registered clinicaltrialsgov nct02200770pmid33771837 doi101212 nxi0000000000000978,0.0
fitness shifts balance bdnf il6 inflammation repair among people progressive multiple sclerosis biomolecules 2021 mar 26 11 4 504 doi 103390 biom11040504abstractphysical sedentarism linked elevated levels circulating cytokines whereas exercise upregulates growthpromoting proteins brainderived neurotrophic factor bdnf shift towards repair phenotype protect neurodegeneration especially diseases multiple sclerosis ms investigated whether higher fitness participating acute bout maximal exercise shift balance bdnf interleukin6 il6 serum samples people progressive ms n 14 compared matched controls n 8 participants performed maximal graded exercise test recumbent stepper blood samples collected rest test assessed walking speed fatigue maximal oxygen consumption vo2max people ms achieved 50 lower vo2max p 0003 controls rest differences bdnf ms controls however il6 significantly higher ms higher vo2max associated shift bdnf il6 ratio inflammation repair r 07 p 0001 considering groups together ms group greater ability upregulate bdnf associated faster walking speed lower vitality present evidence higher fitness indicates shift balance blood biomarkers towards repair phenotype progressive mspmid33810574 doi103390 biom11040504,0.0
shared decision making patients satisfaction strabismus carea pilot study background strabismus complex disease various treatment approaches advantages drawbacks context shared decisions making sdm communication process provider sharing relevant treatment alternatives benefits risks procedure patient shares preferences values regarding choices way sdm bidirectional process goes beyond typical informed consent therefore known little extent sdm influences satisfaction treatment outcome along strabismus patients study correlation sdmq9 questionnaire provided within surgical consultations treatment decisions made sdmq9 aims assess relationship postoperative patients satisfaction smd scoremethodsthe study considered prospective observational pilot study eligible patients adult patients diagnosed strabismus multiple treatment options given right choice without driven physicians preference ninetythree strabismus patients asked fill sdmq9 questionnaire related perception sdm entire period strabismus treatment treatment patients asked rate satisfaction level surgical outcome excellent good fair poor descriptive statistics linear regression statistical tests spearman mann whitney u kriskalwallis used analysis toolsresultsthe average age participants 24 506 women mean sdmq9 score among patients 32 iqr 3 postoperative patient satisfaction rated excellent 16 172 patients good 38 409 fair 32 344 poor 7 patients 75 data analysis linear regression statistical tests showed positive correlation sdmq9 score patient satisfaction related surgery outcome b 0005 p 0001 criteria assessing patients satisfaction age gender strabismus type positive correlation sdm real satisfaction r 0834 p 001 found age significant relationship found taking consideration responders gender strabismus typeconclusionsassessing patient satisfaction choosing treatment strabismus method helped us evaluate gaps constructive dialogue lead positive outcome patient clinician correlation sdm process patients satisfaction surgery outcome adjusted age established findings can serve springboard communicative improvements related sdm process patients physicians thereby consequently leading patients satisfaction raise strabismus care study underlines importance analysis validation onground interactions among adolescent adult patients clinicians across strabismus management trajectory multicentral study validation will follow,0.0
conserved role alslinked splicing factor sfpq repression pathogenic cryptic last exons nat commun 2021 mar 26 12 1 1918 doi 101038 s4146702122098zabstractthe rnabinding protein sfpq plays important role neuronal development associated several neurodegenerative disorders including amyotrophic lateral sclerosis als frontotemporal dementia ftd alzheimers disease report loss sfpq leads premature termination multiple transcripts due widespread activation previously unannotated cryptic last exons cles sfpqinhibited cles appear preferentially long introns genes neuronal functions can dampen gene expression outputs give rise short peptides interfering normal gene functions show one peptide encoded clecontaining epha4b mrna isoform responsible neurodevelopmental defects sfpq mutant uncovered clerepressive activity sfpq conserved mouse human sfpqinhibited cles found expressed across als ipscderived neurons results greatly expand understanding sfpq function uncover gene regulation mechanism wide relevance human neuropathologiespmid33771997 doi101038 s4146702122098z,0.0
overcoming inhibitory microenvironment surrounding oligodendrocyte progenitor cells following experimental demyelination nat commun 2021 mar 26 12 1 1923 doi 101038 s41467021222634abstractchronic demyelination human cns characterized inhibitory microenvironment impairs recruitment differentiation oligodendrocyte progenitor cells opcs leading failed remyelination axonal atrophy networkbased transcriptomics identified sulfatase 2 sulf2 mrna activated human primary opcs sulf2 extracellular endosulfatase modulates signaling microenvironment editing pattern sulfation heparan sulfate proteoglycans found sulf2 increased demyelinating lesions multiple sclerosis actively secreted human opcs experimental demyelination elevated opc sulf1 2 expression directly impaired progenitor recruitment subsequent generation oligodendrocytes thereby limiting remyelination sulf1 2 potentiates inhibitory microenvironment promoting bmp wnt signaling opcs importantly pharmacological sulfatase inhibition using pi88 accelerated oligodendrocyte recruitment remyelination blocking opcexpressed sulfatases findings define important inhibitory role sulf1 2 highlight potential modulation heparanome treatment chronic demyelinating diseasepmid33772011 doi101038 s41467021222634,1.0
selective endocannabinoid reuptake inhibitor wobe437 reduces disease progression mouse model multiple sclerosis acs pharmacol transl sci 2021 mar 26 4 2 765779 doi 101021 acsptsci0c00214 ecollection 2021 apr 9abstractthe modulation endocannabinoid system ecs shown positive results animal models multiple sclerosis ms immune inflammatory disorders however chronic administration cb1 receptor agonists degrading enzyme inhibitors can lead cb1 receptor desensitization sedation wobe437 prototype new class ecs modulators named selective endocannabinoid reuptake inhibitors seris mildly selectively increase central endocannabinoid levels selflimiting mode action previous studies wobe437 demonstrated analgesic anxiolytic antiinflammatory effects tested therapeutic potential wobe437 clinically relevant mouse model ms experimental autoimmune encephalomyelitis c57bl 6 mice administered wobe437 10 mg kg 20 days vehicle using two therapeutic options 1 starting treatment disease onset 2 reaching peak disease strategies wobe437 significantly reduced disease severity accelerated recovery cb1 cb2 receptordependent mechanisms peak disease wobe437 increased endocannabinoid levels cerebellum concurring reduction central nervous system cns infiltrating immune cells lower microglial proliferation end treatment endocannabinoid levels mildly increased brain cerebellum plasma wobe437treated mice without desensitization cb1 receptor brain cerebellum mouse model spasticity straub test wobe437 10 mg kg induced significant muscle relaxation without eliciting typical sedative effects associated muscle relaxants cb1 receptor agonists collectively results show wobe437 seris may represent novel therapeutic strategy slowing ms progression control major symptomspmid33860200 pmcpmc8033750 doi101021 acsptsci0c00214,0.0
structurefunction relationship retinal ganglion cells multiple sclerosis int j mol sci 2021 mar 26 22 7 3419 doi 103390 ijms22073419abstractthe retinal ganglion cells rgc may considered easily accessible pathophysiological site degenerative processes neurological diseases rgc damage detectable multiple sclerosis ms patients hon without history optic neuritis non aimed assess interrelate rgc functional structural damage different retinal layers retinal sites included 12 non patients 11 hon patients 14 healthy controls crosssectional multifocal pattern electroretinography mfperg optical coherence tomography oct measurements amplitude peak times mfperg assessed macula disc oct scans acquired determine macular retinal layer peripapillary retinal nerve fiber layer prnfl thickness hon non patients foveal n2 amplitude mfperg reduced compared controls parafoveal p1 peak time significantly reduced hon oct parafoveal pfgcl perifoveal pgcl ganglion cell layer thicknesses decreased hon vs controls prnfl papillomacular bundle sector pmb showed reductions non hon mfperg derived n2 originates rgc axons findings suggest foveal axonal dysfunction hon also non patientspmid33810342 doi103390 ijms22073419,0.0
microglial pgc1 protects ischemic brain injury suppressing neuroinflammation background neuroinflammation immune responses occurring minutes hours stroke associated brain injury acute ischemic stroke ais ppar coactivator1 pgc1 master coregulator gene expression mitochondrial biogenesis found transiently upregulated microglia ais however role microglial pgc1 poststroke immune modulation remains unknownmethodspgc1 expression microglia human mouse brain samples following ischemic stroke first determined subsequently employed transgenic mice microgliaspecific overexpression pgc1 middle cerebral artery occlusion mcao morphology gene expression profile microglia pgc1 overexpression evaluated downstream inflammatory cytokine production nlrp3 activation also determined chipseq analysis performed detect pgc1binding sites microglia autophagic mitophagic activity monitored immunofluorescence staining unc51like autophagy activating kinase 1 ulk1 expression evaluated pgc1 interaction err finally pharmacological inhibition genomic knockdown ulk1 performed estimate role ulk1 mediating mitophagic activity ischemic strokeresultspgc1 expression shortly increased ischemic stroke human brain samples also mouse brain samples microgliaspecific pgc1 overexpressing mice exhibited significantly decreased neurologic deficits ischemic injury reduced nlrp3 activation proinflammatory cytokine production chipseq analysis kegg pathway analysis revealed mitophagy significantly enhanced pgc1 significantly promoted autophagic flux induced autolysosome formation specifically autophagic clearance mitochondria enhanced pgc1 regulation indicating important role mitophagy pharmacological inhibition knockdown ulk1 expression impaired autophagic mitophagic activity thus abolishing neuroprotective effects pgc1conclusionsmechanistically ais pgc1 promotes autophagy mitophagy ulk1 reduces nlrp3 activation findings indicate microglial pgc1 may promising therapeutic target ais,1.0
much ado nothing offtarget amplification can lead falsepositive bacterial brain microbiome detection healthy parkinsons disease individuals background recent studies suggested existence poly microbial infections human brains described either putative pathogens linked neuroinflammatory changes seen parkinsons disease pd alzheimers disease ad brain microbiome context healthy patients brain samplesmethodsusing 16s rrna gene sequencing tested hypothesis bacterial brain microbiome evaluated brain samples healthy human subjects individuals suffering pd olfactory bulb prefrontal cortex well murine brains line stateoftheart recommendations included several negative positive controls analysis estimated total bacterial biomass 16s rrna gene qpcrresultsamplicon sequencing detect bacterial signals human murine samples estimated bacterial biomass extremely low samples stringent reanalyses implied bacterial signals explained combination exogenous dna contamination 548 false positive amplification host dna 342 offtarget amplicons several seemingly brainenriched microbes dataset turned falsepositive signals upon closer examinationwe identified offtarget amplification major confounding factor lowbacterial highhostdna scenarios amplified human mouse dna sequences clustered falsely assigned bacterial taxa majority tested amplicon sequencing pipelines offtarget amplicons seemed related tissues sterility also found independent brain 16s rrna gene sequencesconclusionstaxonomic signals obtained extremely low biomass samples 16s rrna gene sequencing must scrutinized closely exclude possibility offtarget amplifications amplicons can appear enriched biological samples sometimes assigned bacterial taxa sequences must explicitly matched possible background genomes present large quantities ie host genome using close scrutiny approach find evidence supporting hypothetical presence either brain microbiome bacterial infection pd brains video abstract,0.0
metaanalysis genomewide dna methylation identifies shared associations across neurodegenerative disorders background people neurodegenerative disorders show diverse clinical syndromes genetic heterogeneity distinct brain pathological changes studies report overlap features dna methylation dnam provides way explore overlap heterogeneity determined combined effects genetic variation environment study aim identify shared blood dnam differences controls people alzheimers disease amyotrophic lateral sclerosis parkinsons diseaseresultswe use mixedlinear model method moment accounts effect un known confounders test association dnam site disorder three probes found genomewide significant moment association analysis amyotrophic lateral sclerosis parkinsons disease none alzheimers disease fixedeffects metaanalysis three disorders results 12 genomewide significant differentially methylated positions predicted immune celltype proportions disrupted across neurodegenerative disorders protein inflammatory markers correlated profile sumscores derived diseaseassociated immune celltype proportions healthy aging cohort contrast correlated moment dnamderived profile sumscores calculated using effect sizes 12 differentially methylated positions weightsconclusionswe identify shared differentially methylated positions whole blood neurodegenerative disorders point shared pathogenic mechanisms shared differentially methylated positions may reflect causes consequences disease unlikely reflect celltype proportion differences,0.0
regulation autophagy micrornas human breast cancer abstractbreast cancer common solid cancer affects female population globally micrornas mirnas short noncoding rnas can regulate posttranscriptional modification multiple downstream genes autophagy conserved cellular catabolic activity aims provide nutrients degrade unusable macromolecules mammalian cells number vitro vivo clinical studies reported mirnas modulate autophagy activity human breast cancer cells influence human breast cancer progression treatment response therefore review aimed discuss roles autophagyregulating mirnas influencing breast cancer development treatment response review first introduce autophagy types process followed discussion roles different mirnas modulating autophagy human breast cancer explore mirnaautophagy regulatory process affect disease progression treatment response lastly potential applications challenges utilizing autophagyregulating mirnas breast cancer biomarkers novel therapeutic agents discussed,0.0
diseaseassociated metabolic alterations impact satellite cells muscle regeneration perspectives therapeutic outlook abstractmany chronic disease patients experience concurrent loss lean muscle mass skeletal muscle dynamic tissue maintained continuous protein turnover progenitor cell activity muscle stem cells satellite cells differentiate process called myogenesis fuse repair regenerate muscle myogenesis satellite cells undergo extensive metabolic alterations therefore pathologies characterized metabolic derangements potential impair myogenesis consequently exacerbate skeletal muscle wasting diseaseassociated metabolic disruptions satellite cells might contributing wasting important question largely neglected review highlight impact various metabolic disruptions disease myogenesis skeletal muscle regeneration also discuss metabolic therapies potential improve myogenesis skeletal muscle regeneration ultimately muscle mass,0.0
health care providers experiences pain management attitudes towards digitally supported selfmanagement interventions chronic pain qualitative study background chronic pain constitutes significant burden individuals affected frequent reason patients seek health care services inperson psychosocial interventions can support people living chronic pain interventions always accessible ehealth interventions may provide greater accessibility evidence use digital selfmanagement solutions chronic pain still limited lack health care provider input development process solutions concern therefore aim current study investigate health care providers experiences treating patients chronic pain attitudes towards use digital solutions pain management suggestions content design elements potential digital pain selfmanagement interventionmethodstwelve health care providers representing variety health care disciplines participated semistructured interviews interviews analyzed using thematic analysisresultsthe material analyzed three main themes 1 patients chronic pain current use health care services 2 health care providers motivation impression patient prerequisites use digital selfmanagement interventions 3 suggestions content design elements digital selfmanagement intervention people living chronic pain challenges faced patients living chronic pain described numerous despite interest positive attitudes health care providers used recommended ehealth solutions patients range potential content functionality elements identified including aspects motivation engagement providers also emphasized importance easy access positive personal content support existing treatmentconclusionsthis study offers insights health care providers considerations potential digital selfmanagement interventions supporting patients living chronic pain findings indicate need change comprehensive treatment approach pain management ehealth solutions may contribute change providers pointed need health care provider involvement timely support followup important factors integrating digital pain selfmanagement interventions clinical caretrial registrationclinicaltrialsgov nct03705104,0.0
structural basis tirasemtiv activation fast skeletal muscle j med chem 2021 mar 11 doi 101021 acsjmedchem0c01412 online ahead printabstracttroponin regulates calciummediated activation skeletal muscle muscle weakness diseases amyotrophic lateral sclerosis spinal muscular atrophy occurs diminished neuromuscular output first direct fast skeletal troponin activator tirasemtiv amplifies response muscle neuromuscular input tirasemtiv binds selectively strongly fast skeletal troponin slowing rate calcium release sensitizing muscle calcium report solution nmr structure tirasemtiv bound fast skeletal troponin ctroponin chimera structure reveals tirasemtiv binds hydrophobic pocket regulatory domain troponin c switch region troponin overlaps anapoe xray structure skeletal troponin multiple interactions stabilize troponin ctroponin interface increase affinity troponin c switch region fast skeletal troponin drive equilibrium toward active statepmid33703886 doi101021 acsjmedchem0c01412,0.0
chronic exposure pm25 aggravates sle manifestations lupusprone mice background air pollution causes negative impacts health systemic lupus erythematosus sle autoimmune disease diverse clinical manifestations multifactorial etiology recent studies suggest air pollution can trigger sle induce disease activity however association deeply investigated thus aim study evaluate whether exposure fine particulate matter pm25 exacerbates sle manifestations focusing renal complications lupusprone animal model female nzbwf1 mice exposed daily 600 g m3 inhaled concentrated ambient particles cap filtered air fa survival rate body weight weight organs kidney spleen thymus liver heart blood cell count proteinuria kidney stereology renal histopathology gene expression oxidative stress analyzedresultsfemale nzbw mice exposed cap showed decreased survival increased circulating neutrophils early onset proteinuria increased kidney weight renal cortex enlargement compared nzbw mice exposed faconclusionsthis work shows air pollution aggravates sle manifestations lupusprone mice results reinforce need reducing air pollutant levels order promote better quality life individuals diagnosed sle,0.0
machine learning associated respiratory oscillometry computeraided diagnosis system detection respiratory abnormalities systemic sclerosis abstractintroductionthe use machine learning ml methods improve diagnosis respiratory changes systemic sclerosis ssc paper evaluates performance several ml algorithms associated respiratory oscillometry analysis aid diagnostic respiratory changes ssc also find best configuration taskmethodsoscillometric spirometric exams performed 82 individuals including controls n 30 patients systemic sclerosis normal n 22 abnormal n 30 spirometry multiple instance classifiers different supervised machine learning techniques investigated including knearest neighbors knn random forests rf adaboost decision trees adab extreme gradient boosting xgb results discussionthe first experiment study showed best oscillometric parameter bop dynamic compliance provided moderate accuracy auc 077 scenario control group versus patients sclerosis normal spirometry cgvspsns scenario control group versus patients sclerosis altered spirometry cgvspsas bop obtained high accuracy auc 094 second experiment ml techniques used cgvspsns knn achieved best result auc 090 significantly improving accuracy comparison bop p 001 cgvspsas rf obtained best results auc 097 also significantly improving diagnostic accuracy p 005 third fourth fifth sixth experiments different feature selection techniques allowed us spot best oscillometric parameters resulted small increase diagnostic accuracy cgvspsns respectively 087 086 082 084 cgvspsas best classifiers performance remained auc 097 conclusionsoscillometric principles combined machine learning algorithms provide new method diagnosing respiratory changes patients systemic sclerosis present studys findings provide evidence combination may help early diagnosis respiratory changes patients,0.0
cerebrospinal fluid cells immune landscape multiple sclerosis background multiple sclerosis ms potentially devastating autoimmune neurological disorder characteristically induces demyelination white matter brain spinal cordmethodsin study three characteristics central nervous system cns immune microenvironment occurring ms onset explored immune cell proportion alteration differential gene expression profile related pathways raw data two independent datasets obtained arrayexpress database emtab69 used derivation cohort emtab2374 used validation cohort differentially expressed genes degs identified false discovery rate fdr value 005 log2 fold change 1 analysis functional enrichment analyses performed explore pathways associated ms onset gene expression profiles analyzed using cibersort identify immune type alterations involved ms diseaseresultsafter verification proportion five types immune cells plasma cells monocytes macrophage m2 neutrophils eosinophils cerebrospinal fluid csf revealed significantly altered ms cases compared control group thus complement coagulation cascades systemic lupus erythematosus sle pathways may play critical roles ms identified nlrp3 lilrb2 c1qb cd86 c1qa csf1r il1b tlr2 eight core genes correlated msconclusionsour study identified change cns immune microenvironment ms cases analysis silico data using cibersort data may assist providing directions research molecular mechanisms ms provide future potential therapeutic targets treatment,1.0
variability phenotype response treatment chronic nonbacterial osteomyelitis irish experience national cohort background chronic nonbacterial osteomyelitis cno autoinflammatory disease affecting bone considerable phenotypic heterogeneity variable association autoinflammatory conditions disease pathogenesis incompletely understood treatment protocols vary physicians clinical treatment guidelines available prior 2017 although cno previously considered benign now clear longterm sequelae occurthe aim study provide detailed phenotypic description children adolescents cno attended tertiary paediatric rheumatology services ireland september 2017 september 2019 disease course treatment outcomesmethodsthis study involved retrospective review clinical notes laboratory radiology histology results irish children adolescents cno currently attending tertiary paediatric rheumatology services bristol diagnostic criteria applied retrospectively patients met criteria included criteria remission partial response based childhood arthritis rheumatology research alliance carra criteria treatment failureresultsfortyfour children adolescents recruited demographics terms age onset gender number sites similar previously reported overall 18 44 409 extraosseous manifestations associated cno 12 44 272 cutaneous involvement patients received regular nonsteroidal antiinflammatory drug nsaid diagnosis 27 44 614 requiring least 1 secondline medication secondline agents used cohort bisphosphonates methotrexate tnfblockers patients received systemic corticosteroidsconclusionthis national cohort showed high prevalence extraosseous involvement low response rate nsaid treatment may reflect inflammatory phenotype highlights need define different subtypes cno,0.0
serum neurofilament light chain measurement ms hurdles clinical translation front neurosci 2021 mar 25 15654942 doi 103389 fnins2021654942 ecollection 2021abstractmeasurement serum neurofilament light chain concentration snfl promises become convenient cost effective meaningful adjunct multiple sclerosis ms prognostication well monitoring disease activity response treatment despite remarkable progress everincreasing literature supporting potential role snfl ms last 5 years number hurdles remain test can integrated routine clinical practice review highlight hurdles broadly classified concerns relating clinical validity analytical validity setting aspirational roadmap many issues can overcome conclude sharing vision current future role snfl assays ms clinical practicepmid33841093 pmcpmc8027110 doi103389 fnins2021654942,0.0
creactive protein suppresses th17 response indirectly attenuating antigen presentation ability monocyte derived dendritic cells experimental autoimmune encephalomyelitis front immunol 2021 mar 25 12589200 doi 103389 fimmu2021589200 ecollection 2021abstractexperimental autoimmune encephalomyelitis eae classical murine model multiple sclerosis ms human autoimmune disease characterized th1 th17 responses numerous studies reported creactive protein crp mitigates eae severity studies relevant pathologic mechanisms insufficient previous study found crp suppresses th1 response directly receptor binding nave t cells however observe effect th17 response time thus remains unclear whether crp regulate th17 response study verified downregulation th17 response singledose crp injection mogimmunized eae mice vivo direct indirect effects crp th17 response differentiated comparing actions isolated cd4+ t cells splenocytes vitro respectively moreover immune cell composition examined blood cns central nervous system blood monocytes cns dendritic cells infiltration pathway established course eae development infiltrated monocyte derived dcs modcs proved candidate antigen presenting cells execute crps function conversely decrease th17 responses caused crp disappeared vivo vitro studies fcr2b mice indicating fcr2b expressed modcs mediates crp function furthermore peripheral blood monocytes isolated induced establish modcs used demonstrate antigen presenting ability modcs attenuated crp fcr2b nfb erk signaling pathways manifested involved regulation ultimately perfected enriched mechanism studies crp eae remission convinced crp plays key role protecting eae development may potential therapeutic target treatment ms humanpmid33841391 pmcpmc8027258 doi103389 fimmu2021589200,0.0
bilateral onestage singleport sympathicotomy primary focal hyperhidrosis prospective cohort study treat earlier background primary focal hyperhidrosis pfh detrimental effect quality life repetitive noncurative symptomatic strategies dominate current treatment pfh spite availability effective permanent curative treatment like endoscopic thoracic sympathectomy ets current surgical optimization may allow reestablished position sympathetic modulation treatment algorithm sought evaluate safety effectiveness longterm results bilateral onestage singleport sympathicotomy boss procedure pfh patients identify subgroups benefitting mostmethodsprospective analysis 163 patients 35 215 underwent rib3 r3 boss palmar pfh 58 356 r3r5 boss axillary pfh 70 429 r3r5 boss combined palmar axillary pfh effectiveness measured using skindex29 hyperhidrosis disease severity scale hdss resultsoverall skindex29rating 465 148 preoperatively vs 201 206 postoperatively p 0001 hdss score 371 045 preoperatively vs 182 086 postoperatively p 0001 indicated significant improvement healthrelated quality life boss r3 boss superior r3r5 boss terms hdss score 149 vs 191 respectively p 0004 terms severe compensatory hyperhidrosis frequently reported sideeffect 171 vs 328 respectively p 0001 major complications occurredconclusionsboss safe effective offers longterm curative solution treatment pfh especially palmar pfh subgroup r3 boss treatment results compare favorably treatment results noncurative alternatives published current literature therefore r3 boss offered patients severe pfh reporting insufficient benefit treatment options oral local agents,0.0
prediction timesensitive condition among patients dizziness assessed emergency medical services background dizziness relatively common symptom among patients call emergency medical services ems aimto identify factors importance early identification timesensitive condition behind symptom dizziness among patients assessed emsmethodsall patients assessed ems triaged using rapid emergency triage treatment retts adults code 11 dizziness 660 000 inhabitants municipality gothenburg sweden 2016 considered inclusion patients divided two groups according final diagnosis timesensitive condition yes resultsthere 1536 patients fulfilled inclusion criteria 96 62 timesensitive condition majority stroke transitory ischaemic attack tia eight predictors timesensitive condition identified three associated reduced risk 1 dizziness rotatory type 2 dizziness sudden onset 3 increasing body temperature five associated increased risk 1 sudden onset headache 2 history head trauma 3 symptoms nausea vomiting 4 treatment anticoagulants 5 increasing systolic blood pressureconclusionamong 1536 patients triaged ems dizziness 62 timesensitive condition arrival ems eight factors associated risk timesensitive condition factors linked type symptoms clinical findings arrival ems recent clinical history,0.0
extended interval dosing natalizumab preserve effectiveness multiple sclerosis 7 yearretrospective observational study front immunol 2021 mar 25 12614715 doi 103389 fimmu2021614715 ecollection 2021abstractthe extended interval dosing eid natalizumab suggested associated reduced risk progressive multifocal leukoencephalopathy pml shortterm preservation efficacy longterm effectiveness remain unknown aimed determine longterm effectiveness safety natalizumab eid setting cohort patients multiple sclerosis ms treated 7 years conducted observational retrospective cohort study including 39 34 female 5 male patients clinically definite relapsingms initially treated standard interval dosing sid natalizumab mean time 54 months sd29 switched eid every 8 weeks mean time 76 months sd13 main outcome measures included following annualized relapse rate arr ii radiological activity iii disability progression iv neda3 evidence disease activity index eid preserved arr radiological activity prevented disability worsening followup proportion patients maintaining neda3 status 24 48 72 months natalizumab administration eid 94 73 70 respectively stratified analysis according history drug therapy showed eid natalizumab slightly effective nave patients previously treated immunosuppressive drugs cases pml severe adverse reactions reported conclusion longterm therapy natalizumab eid setting following sid regimen maintained diseasemodifying activity safe well tolerated 7 years encouraging observational results need confirmed controlled clinical trialspmid33841397 pmcpmc8027344 doi103389 fimmu2021614715,0.0
survival function il10producing regulatory b cells negatively controlled slamf5 nat commun 2021 mar 25 12 1 1893 doi 101038 s4146702122230zabstractb cells essential functions multiple sclerosis mouse model experimental autoimmune encephalomyelitis drivers suppressors disease suppressive effects driven regulatory b cell breg population functions primarily exclusively via production il10 however mechanisms modulating il10producing breg abundance poorly understood identify slamf5 controlling il10+ breg maintenance function eae deficiency slamf5 b cells causes accumulation il10+ bregs central nervous system periphery blocking slamf5 vitro induces human mouse il10producing breg cells increases survival concomitant increase transcription factor cmaf finally vivo slamf5 blocking eae elevates il10+ breg levels ameliorates disease severity results suggest slamf5 negative moderator il10+ breg cells may serve therapeutic target ms autoimmune diseasespmid33767202 doi101038 s4146702122230z,0.0
beliefs medication predictors medication adherence prospective cohort study among persons multiple sclerosis bmc neurol 2021 mar 25 21 1 136 doi 101186 s12883021021490abstractbackground though adherence diseasemodifying therapies dmts among persons multiple sclerosis pwms varies often 80 prospective studies adherence examined predictors beyond demographic clinical characteristicsobjectives identify antecedents adherence persistence dmt prospective design among pwmsmethods pwms n 186 prospectively assessed three time points baseline 6 time 1 12 months later time 2 clinical demographic information patientreported medication beliefs illness perceptions medication habits perceived health affect surveyed inperson adherence persistence assessed combination selfreports retrospective review medication claimsfindings pwms 699 time 1 71 time 2 adherent dmts 6459 persistent beliefs medications consistently predictive time points baseline time 1 time 1 time 2 medication adherence persistence whereas perceptions predictive analyses clinical demographic characteristics mostly predictive adherence persistence prospective association beliefs medication adherence held also multivariate analyses 088 95 ci 078099 p 0029 conclusions adherence persistence predicted medication beliefs pwms medication beliefs modifiable assessed periodically targeted focus tailored interventions aimed improve adherence consequently health outcomes pwmsregistration clinical trials registry # nct02488343 date 06 08 2015pmid33761887 doi101186 s12883021021490,0.0
p57kip2 nuclear export marker oligodendrocytes differentiation towards innovative phenotyping screening identification myelin repair drugs article kry collaborators published ebiomedicine demonstrates first time worth innovative phenotyping screening identification myelin repair drugs 1 original approach based previous identification research group cyclin dependent kinase inhibitor p57kip2 main intrinsic negative regulator schwann cell 2 oligodendrocytes differentiation 3 glial cells involved peripheral central nervous system cns myelination respectively 4 particular subcellular translocation p57kip2 leads oligodendrocytes precursor cells opcs differentiation myelin formation therefore phenotypic screening proposed particularly suitable identify molecules able induce myelination aim counteract demyelination 1 demyelinating diseases affecting nervous system variety etiologies can classified primary disorders multiple sclerosis ms idiopathic inflammatorydemyelinating diseases secondary disorders can originated infectious ischemic metabolic toxic causes common demyelinating disease ms progressive inflammatory autoimmune disorder characterised inflammatory cells infiltration demyelination gliosis axonal loss affecting optic nerves brainstem spinal cord cerebellar subcortical white matter thus resulting chronic progressive motor disabilities well cognitive psychiatric disturbances 5 ms affects 2 million people worldwide twice many women men primarily younger adults average onset age 30 years 25 years diagnosis half patients will require permanent wheelchair use ms represents crucial medical social economic problem absolutely requires addressed fact cure now available pharmacological treatments can relieve symptoms 6 thus urgent need specific drug development treat ms demyelinating disorders actually two principal rational approaches ms drug development counteracting demyelination promoting remyelination approaches mutually exclusive can directed either towards immune cells reduce inflammation modulate activation towards oligodendrocytes induce myelination remyelination 7 8 oligodendrocytes glial cells derived neural stem cells nscs opcs differentiate produce myelin sheet wrap neurons allowing fast axonal conduction supporting neuronal survival function myelination physiological process massively takes place postnatal development differentiated cns remyelination continuously occurs life especially injuries due many different pathological causes ms inflammatory events determine demyelination thereby remyelination necessary repair damage protect neurons first remyelination requires oligodendrocytes differentiation therefore new frontier therapeutic approaches counteract ms identification drug candidates able induce oligodendrocytes differentiation 9 framework screening procedure proposed kry collaborators useful identify new compounds also drug repurposing particularly interesting fast development new therapeutic approaches fact authors clearly demonstrated subcellular localization p57kip2 easily allows identifying prodifferentiation promyelinating molecules rodent opcs tested ex vivo vivo models ie organotypic cerebellar slices cuprizonemouse model demyelination respectively 1 role cell cycle inhibitor depends subcellular localisation nuclear accumulation p57kip2 blocks differentiation opcs therefore myelination nuclear export leads oligodendrocytes differentiation therefore myelination 10 thus subcellular localisation p57kip2 might used marker myelinations induction well readout screen molecules myelin repair successfully shown issue fact approach library 1000 fdaapproved compounds rapidly tested leading identification 21 molecules able enhance p57kip2 nuclear export primary rodent opcs among compounds already identified involved opcs differentiation pathways selected demonstrating validity phenotypic screening molecules also tested opcs differentiation analysis myelin protein expression thus selecting 4 compounds analysed promyelinating effect vitro model primary human opcs ex vivo model organotipic slices vivo rat cuprizone model de remyelination approach allowed unequivocally identifying 2 compounds able enhance remyelination different models ie parbendazole danazol respectively fdaapproved drugs anthelmintic treatment endometriosis 1 thus kry collaborators clearly demonstrated phenotypic screening based p57kip2 nuclear export powerful approach can extended larger libraries identify compounds able induce opcs differentiation therefore myelination counteract ms devastating demyelinating disorders urgent unmet medical need,1.0
neuronal cellbased highthroughput screen enhancers mitochondrial function reveals luteolin modulator mitochondriaendoplasmic reticulum coupling background mitochondrial dysfunction common feature aging neurodegeneration metabolic diseases hence mitotherapeutics may valuable disease modifiers large number conditions study set largescale screening platform mitochondrialbased modulators promising therapeutic potentialresultsusing differentiated human neuroblastoma cells screened 1200 fdaapproved compounds identified 61 molecules significantly increased cellular atp without cytotoxic effect following dose response curvedependent selection identified flavonoid luteolin primary hit validation neuronal models indicated luteolin increased mitochondrial respiration primary neurons despite affecting mitochondrial mass structure mitochondriaderived reactive oxygen species however found luteolin increased contacts mitochondria endoplasmic reticulum er contributing increased mitochondrial calcium ca2+ ca2+dependent pyruvate dehydrogenase activity signaling pathway likely contributed observed effect luteolin enhanced mitochondrial complexes ii activities importantly observed increased mitochondrial functions dependent activity er ca2+releasing channels inositol 1 4 5trisphosphate receptors ip3rs neurons isolated synaptosomes additionally luteolin treatment improved mitochondrial locomotory activities primary neurons caenorhabditis elegans expressing expanded polyglutamine tract huntingtin proteinconclusionwe provide new screening platform drug discovery validated vitro ex vivo addition describe novel mechanism luteolin modulates mitochondrial activity neuronal models potential therapeutic validity treatment variety human diseases,0.0
therapeutic effects noninvasive individualized transcranial neuromodulation treatment voiding dysfunction multiple sclerosis patients study protocol pilot clinical trial pilot feasibility stud 2021 mar 24 7 1 83 doi 101186 s4081402100825zabstractbackground voiding dysfunction vd common neurogenic lower urinary tract dysfunction nlutd multiple sclerosis ms patients currently effective management vd urinary retention ms patients catheterization prompting us look novel therapeutic options beyond bladder brain transcranial rotating permanent magnet stimulator trpms noninvasive portable multifocal neuromodulator simultaneously modulates multiple cortical regions enhancing attenuating strengths functional connections regions objective pilot clinical trial evaluate feasibility trpms trial address lower urinary tract symptoms ms patients investigating therapeutic effects trpms modulating brain regions voiding initiation mitigating vd female ms individualsmethods ten adult female ms patients vd defined postvoid residual bladder capacity pvr bc 40 liverpool nomogram percentile 10 will recruited study concurrent urodynamic functional mri evaluation bladder filling emptying task repeated three four times will performed baseline posttreatment predetermined regions interest bloodoxygenleveldependent bold activation voiding initiation will identified patients baseline anatomical functional mri scan corresponding microstimulators placement individualized trpms treatment cap either stimulate inhibit regions patients will receive 10 40min treatment sessions noninstrumented uroflow validated questionnaires will also collected baseline posttreatment evaluate clinical improvementdiscussion despite crucial role central nervous system urinary control sensitivity ms treatment urinary dysfunction targeting brain centers involved proper bladder function trial knowledge will first kind humans consider noninvasive individualized cortical modulation treating vd ms patients results study will provide better understanding brain control neurogenic bladders lay foundation potential alternative therapy vd ms patients nlutd larger neurogenic population futuretrial registration trial registered clinicaltrialsgov nct03574610 2 july 2018 houston methodist research institute irb pro00019329 pmid33757581 doi101186 s4081402100825z,0.0
advances intranasal application stem cells treatment central nervous system diseases abstractstem cells characterized selfrenewal multipotency great potential therapy various disorders however bloodbrain barrier bbb limits application stem cells therapy neurological disorders especially noninvasive way shown small molecular substances macromolecular proteins even stem cells can bypass bbb reach brain parenchyma following intranasal administration review possible brainentry routes transnasal treatment cell types diseases involved intranasal stem cell therapy discuss advantages disadvantages treatment central nervous system diseases provide reference application intranasal stem cell therapy,0.0
epigallocatechin gallate relapsingremitting multiple sclerosis randomized placebocontrolled trial neurol neuroimmunol neuroinflamm 2021 mar 24 8 3 e981 doi 101212 nxi0000000000000981 print 2021 mayabstractobjective assess safety efficacy epigallocatechin3gallate egcg addon glatiramer acetate ga patients relapsingremitting multiple sclerosis rrms methods enrolled patients rrms aged 1860 years expanded disability status scale edss score 065 receiving stable ga treatment multicenter prospective doubleblind phase ii randomized controlled trial participants received 800 mg oral egcg daily period 18 months primary outcome proportion patients without new hyperintense lesions t2weighted t2w brain mri within 18 months secondary end points included additional mri clinical parameters immunologic effects egcg investigated exploratory experimentsresults total 122 patients ga randomly assigned egcg treatment n 62 placebo n 60 demonstrate difference groups 18 months primary outcome radiologic t2w lesion volume t1w hypointense lesion number volume number cumulative contrastenhancing lesions percent brain volume change clinical edss ms functional composite annualized relapse rate parameter egcg treatment affect immune response ga pharmacologic analysis revealed wide ranging egcg plasma levels treatment well tolerated similar incidence mostly mild adverse events similar groupsconclusion rrms oral egcg addon ga superior placebo influencing mri clinical disease activity 18 months treatment safe daily dosage 800 mg egcg influence immune parameters despite indication egcg bioavailable patientsclassification evidence study provides class ii evidence patients rrms egcg added ga significantly affect development new hyperintense lesions t2weighted brain mritrial registration information clinical trial registration number nct00525668pmid33762428 doi101212 nxi0000000000000981,0.0
early alterations neurovascular unit retina mouse models tauopathy abstractthe retina visually accessible tissue central nervous system attracted significant attention evaluating biomarker neurodegenerative diseases yet studies focus characterizing loss retinal ganglion cells rgcs degeneration axons integrated analysis addressing temporal alterations different retinal cells neurovascular unit nvu particular retinal vessels assessed nvu changes two mouse models tauopathy p301s p301l transgenic mice overexpressing human tau mutated gene evaluated therapeutic effects tau oligomer monoclonal antibody toma found retinal edema breakdown bloodretina barrier observed early stage tauopathy leukocyte adhesion infiltration microglial recruitment activation constantly increased retinal ganglion cell layer tau transgenic mice different ages mller cell gliosis detected relatively older tau mice concomitantly number function rgcs progressively decreased aging although considerably altered early stage tauopathy moreover intrinsically photosensitive rgcs appeared sensitive tauopathy remarkably toma treatment young tau transgenic mice significantly attenuated vascular leakage inflammation rgc loss data provide compelling evidence abnormal tau accumulation can lead pathology retinal nvu vascular alterations occur manifest earlier neurodegeneration retina oligomeric tautargeted immunotherapy potential treat tauinduced retinopathies data suggest retinal nvu may serve potential biomarker diagnosis staging tauopathy well platform study molecular mechanisms neurodegeneration,0.0
tdp43 proteinopathy alters ribosome association multiple mrnas including glypican dallylike protein dlp gpc6 abstractamyotrophic lateral sclerosis als genetically heterogeneous neurodegenerative disease 97 patients exhibit cytoplasmic aggregates containing rna binding protein tdp43 using tagged ribosome affinity purifications drosophila models tdp43 proteinopathy identified tdp43 dependent translational alterations motor neurons impacting spliceosome pentose phosphate oxidative phosphorylation pathways subset mrnas altered ribosome association also enriched tdp43 complexes suggesting may direct targets among dlp mrna encodes glypican dally like protein dlp gpc6 wingless wg wnt signaling regulator insolubilized flies patient tissues tdp43 pathology dlp gpc6 forms puncta drosophila neuropil als spinal cords reduced neuromuscular synapse flies suggesting compartment specific effects tdp43 proteinopathy findings together genetic interaction data show dlp gpc6 novel physiologically relevant target tdp43 proteinopathy,0.0
evidences adult hippocampal neurogenesis humans rodent hippocampus generates new neurons throughout life process named adult hippocampal neurogenesis ahn striking form neural plasticity occurs brains numerous mammalian species direct evidence adult neurogenesis humans remained elusive although occurrence phenomenon human dentate gyrus demonstrated seminal studies recent research applied distinct approaches birthdate newly generated neurons validate markers adultborn neurons data point persistence ahn 10th decade human life well marked impairments process patients alzheimers disease moreover work demonstrates methods used process analyze postmortem human brain samples can limit detection various markers ahn point making undetectable dual perspectives article highlight critical methodological aspects strictly controlled human studies robust evidence supports occurrence ahn humans also put forward reasons may account current discrepancies topic finally unresolved questions future challenges awaiting field highlighted,0.0
neurological causes chest pain curr pain headache rep 2021 mar 24 25 5 32 doi 101007 s11916021009445abstractpurpose review chest pain common presenting complaint among patients hospital large proportion noncardiac chest pain nccp neurological causes nccp previously reviewed although several causes identifiedrecent findings chest pain reported symptom multiple neurological conditions migraine epilepsy multiple sclerosis varying clinical presentations affected patients often formally diagnosed long periods time due difficulties recognizing symptoms part neurological disease processes paper will briefly summarize wellknown etiologies chest pain review neurological causes nccp providing overview current literature possible pathophysiologic mechanismspmid33760994 doi101007 s11916021009445,0.0
stem cell therapy treatment autoimmune diseaseupdates lupus scleroderma multiple sclerosis curr allergy asthma rep 2021 mar 24 21 3 22 doi 101007 s1188202100996yabstractpurpose review evidence hematopoietic stem cell transplantation hct autoimmune disease building since 1990s however many clinicians may yet aware applications autoimmune disease review basic tenets hct evidence autologous hct multiple sclerosis ms systemic sclerosis ssc lupus emphasis recent advanced phase trialsrecent findings ms phase 3 randomized mist trial phase 2 randomized astims trial demonstrated efficacy autologous hct refractory ms diseasemodifying therapies mitoxantrone respectively ssc phase 3 randomized astis trial phase 2 randomized scot trial demonstrated efficacy autologous hct advanced ssc compared cyclophosphamide evidence hct autoimmune diseases continues grow particularly ms ssc lupus large comparative trials still needed across autoimmune diseases questions still remain answered include optimizing patient selection limit trm appropriate use mac necessity graft manipulation furthermore collaboration diseasespecific transplant physicians imperative expand appropriate use hct routine clinical practicepmid33759038 doi101007 s1188202100996y,0.0
oligodendrocytespecific mechanisms myelin thinning implications neurodegenerative diseases front neurosci 2021 mar 24 15663053 doi 103389 fnins2021663053 ecollection 2021no abstractpmid33841096 pmcpmc8024530 doi103389 fnins2021663053,1.0
subacute cerebellar ataxia following respiratory symptoms covid19 case report background severe acute respiratory syndrome virus 2 sarscov2 spreading globally causes frequently fever respiratory symptoms ie coronavirus disease 2019 covid19 however distinct neurological syndromes associated sarscov2 infection described among sarscov2infectionsassociated neurological symptoms fatigue headache dizziness impaired consciousness anosmia ageusia frequent less frequent neurological deficits seizures guillainbarr syndrome ataxia may also occurcase presentationherein present case 62yearold man developed subacute cerebellar syndrome limb truncal gait ataxia scanning speech 1 day clinical resolution symptomatic sarscov2 infection upper airways apart ataxia signs indicative opsoclonus myoclonus ataxia syndrome miller fisher syndrome cerebral magnetic resonance imaging showed mild cerebellar atrophy sarscov2 infection cerebellum excluded normal cerebrospinal fluid cell counts importantly absence sarscov2 rna intrathecal sarscov2specific antibody production causes ataxia viral infections autoimmune paraneoplastic diseases intoxication ruled neurological deficits improved rapidly highdose methylprednisolone therapyconclusionsthe laboratory clinical findings well marked improvement highdose methylprednisolone therapy suggest postinfectious immunemediated cause ataxia report make clinicians aware consider sarscov2 infection potential cause postinfectious neurological deficits atypical clinical presentation consider highdose corticosteroid treatment case postinfectious immunemediated mechanism assumed,0.0
work ability life satisfaction matter return work predictive ability work ability index life satisfaction questionnaire among women longterm musculoskeletal pain background impaired work ability reduced life satisfaction due longterm musculoskeletal pain particularly neck shoulders back considered occupational health problems can result workers taking sick leave aim study determine whether work ability life satisfaction predict return work rtw among women longterm neck shoulder back pain assess ability work ability index wai life satisfaction questionnaire lisat11 discriminate rtw rtw nrtw methodsthis cohort study 1year followup survey sent 600 women receiving sick leave benefits swedish social insurance agency total 208 women responded baseline 141 1year followup identify whether work ability life satisfaction predicted rtw multiple logistic regression analyses performed without adjustment type work pain intensity assess discriminative ability wai lisat11 women rtw nrtw receiver operating characteristic curves fittedresultswork ability predicted rtw results remained significant adjusting type work pain intensity 112 95 ci 104122 life satisfaction significant wai baseline adequately discriminated rtw nrtw 1 year area curve 078 95 ci 070086 lisat11 notconclusionsthis study supports relationship work ability rtw among women sick leave longterm neck shoulder back pain results indicate wai lisat11 can discriminate rtw nrtw population study although discriminative ability wai needs verified new samples can recommended use rehabilitation settings suggest healthcare professionals consider women perceive work ability order better support rtw,0.0
design national genomic projecta systematic review active projects abstractan increasing number countries investing efforts exploit human genome order improve genetic diagnostics pave way integration precision medicine health systems expected benefits include improved understanding normal pathological genomic variation shorter timetodiagnosis costeffective diagnostics targeted prevention treatment research advanceswe review 41 currently active individual national projects concerning aims scope number age structure included subjects funding data sharing goals methods linkage biobanks medical data nonmedical data exposome main aims ongoing projects determine normal genomic variation 90 determine pathological genomic variation rare disease complex diseases cancer etc 71 improve infrastructure 59 enable personalized medicine 37 numbers subjects sequenced ranges substantially hundred million representing cases significant portion population approximately half projects report public funding rest various mixed private funding arrangements 90 projects report data sharing public academic commercial various levels access plan linking genomic data medical data 78 existing biobanks 44 nonmedical data 24 basis enabling personal precision medicine futureour results show substantial diversity analysed categories 41 ongoing national projects overview current designs will hopefully inform national initiatives designing new genomic projects contribute standardisation international collaboration,0.0
presence activation proinflammatory macrophages associated cryab expression vitro peripheral nerve injury background inflammation constitutes positive negative aspects recovery following peripheral nerve injury following damage peripheral nervous system pns immune cells macrophages play beneficial role creating supportive environment regrowing axons phagocytosing myelin axonal debris however prolonged inflammatory response peripheral nerve injury implicated pathogenesis negative symptoms like neuropathic pain therefore postinjury inflammation must carefully controlled prevent secondary damage allowing regeneration cryab also known alphabcrystallin hspb5 small heat shock protein many protective functions including immunomodulatory role mouse models multiple sclerosis spinal cord injury stroke expression wanes rebounds early late periods respectively pns damage cryab null mice sciatic nerve crush injury display symptoms pain investigated whether cryab involved immune response following pns injurymethodssciatic nerve crush injuries performed agematched cryab knockout cryab wildtype wt female mice nerve segments distal injury site processed immunohistochemistry macrophages myelin protein lysates nerves analyzed cytokines chemokines using luminex enzymelinked immunosorbent assay elisa peritoneal macrophages two genotypes also cultured polarized proinflammatory antiinflammatory phenotypes supernatants analyzed cytokines chemokines elisa protein lysates macrophage antigen presenting markers using western blottingresultswe report 1 proinflammatory cd16 32+ macrophages present nerves cryab mice days 14 21 sciatic nerve crushinjury compared wt counterparts 2 cryab immunosuppressive effect cytokine secretion interleukin il il6 il12p40 tumor necrosis factor tnf proinflammatory macrophages vitroconclusionscryab may play role curbing potentially detrimental proinflammatory macrophage response late stages peripheral nerve regeneration,1.0
simultaneous staged operation tandem spinal stenosis surgical strategy efficacy comparison background tandem spinal stenosis tss complex clinical presentation consensus optimal surgical strategy study retrospectively compared efficacy different staged operations simultaneous decompression patients tssmethodswe reviewed data 132 patients tss received surgical procedures january 2011 june 2018 patients classified three groups according symptomatic area compression group c firststage surgery cervical compression group l firststage surgery lumbar compression group cl simultaneous surgery medical records reviewed age gender comorbidities operation time combined estimated blood loss time hospitalization joac joal ndi odi scores complications also examinedresultspostoperative outcomes followed 321 54 months significant differences reoperation rate interval time two types staged operations p 0005 p 0001 respectively significant differences gender p 0639 operation time p 0138 combined estimated blood loss p 0116 complications p 0652 among three groups simultaneous group significantly younger p 0027 fewer comorbidities p 0001 shorter hospitalization time p 0001 final followup joac joal scores increased ndi odi scores decreased compared preoperative scoresconclusionstss can effectively managed either simultaneous staged decompressions firststage surgery cervical stenosis significantly lowers requirement secondstage lumbar surgery onestage simultaneous decompression safe effective advantage reduce hospitalization time without increase operative time bleeding however surgical indications strictly controlled recommended younger patients fewer comorbidities,0.0
antimyelin oligodendrocyte glycoprotein antibodies girl good recovery five episodes prior idiopathic optic neuritis j ophthalmol case rep 2021 mar 24 22101060 doi 101016 jajoc2021101060 ecollection 2021 junabstractpurpose describe clinical radiological immunological electrophysiological features myelin oligodendrocyte glycoprotein mog igg positive girl five prior episodes idiopathic bilateral optic neuritis observations report danish girl followed pediatricians pediatric neurologists since age 10 recurrent episodes idiopathic bilateral since age 15 recurrence patient thoroughly investigated multiple sclerosis ms several times negative findings age 19 patient referred clinic optic neuritis tested seropositive antibodies mog mog igg conventionally cellbased assay despite 5 previous episodes latency amplitude signals patternreversal visual evoked potentials pvep including multifocal vep detected within normal rangeconclusion clinical implications mog igg yet clear cases diagnosis ms less likely main symptom testing igg antibodies aqp4 mog atypical optic neuropathies mind important mogigg positive patients may good prognosis regards visual functionpmid33997466 pmcpmc8100534 doi101016 jajoc2021101060,1.0
association exacerbation phenotype sputum microbiome chronic obstructive pulmonary disease patients clinically stable state background chronic obstructive pulmonary disease copd progressive lifethreatening lung disease increasing prevalence incidence worldwide increasing evidence suggests lung microbiomes might play physiological role acute exacerbations copd objective study characterize association microbiota exacerbation risk airflow limitation stable copd patientsmethodsthe sputum microbiota 78 copd outpatients periods clinical stability investigated using 16s rrna v3v4 amplicon sequencing microbiome profiles compared patients different risks exacerbation ie low risk exacerbator lre high risk exacerbator hre groups different airflow limitation severity ie mild moderate fev1 50 pft severe severe fev1 50 pft ii resultsthe bacterial diversity chao1 observed otus significantly decreased hre group compared lre group top 3 dominant phyla sputum firmicutes actinobacteria proteobacteria similar hre lre groups genus level compared lre group 4124 proportion streptococcus slightly decreased hre group 2868 p 0007 however bacterial diversity proportion dominant bacteria phylum genus levels similar pft pft ii groups furthermore relative abundances gemella morbillorum prevotella histicola streptococcus gordonii decreased hre group compared lre group according linear discriminant analysis effect size lefse microbiome network analysis suggested altered bacterial cooperative regulation different exacerbation phenotypes proportions proteobacteria neisseria negatively correlated fev1 fvc value according functional prediction sputum bacterial communities phylogenetic investigation communities reconstruction unobserved states picrust analysis genes involved lipopolysaccharide biosynthesis energy metabolism enriched hre groupconclusionthe present study revealed sputum microbiome changed copd patients different risks exacerbation additionally bacterial cooperative networks altered hre patients may contribute disease exacerbation results provide evidence sputum microbiome community dysbiosis associated different copd phenotypes hope understanding lung microbiome potentially modifiable clinical factor targets improved copd therapies clinically stable state may elucidated,0.0
juxtacortical susceptibility changes progressive multifocal leukoencephalopathy graywhite matter junction correlates ironenriched macrophages abstractobjectivedescribe magnetic resonance imaging mri susceptibility changes progressive multifocal leukoencephalopathy pml identify neuropathological correlatesmethodspml cases matched controls primary central nervous system lymphoma pcnsl retrospectively identified mri brain 3 t 7 t reviewed mripathology correlations fixed brain autopsy tissue conducted three subjects confirmed pmlresultswith pml n 26 total n 5 multiple sclerosis natalizumabassociated juxtacortical changes susceptibilityweighted imaging swi gradient echo gre sequences noted 3 3 cases 7 t mri 14 22 cases 636 15 t 8 22 364 3 t mri similar findings noted 3 25 120 pcnsl patients odds ratio 1283 95 confidence interval ci 29567 p 0001 15 3 t mri susceptibility sequences available prior diagnosis pml 7 875 changes present average 27 18months mean sd prior diagnosis postmortem 7 t mri showed swi changes corresponded areas increased iron density along graywhite matter gmwm junction predominantly macrophagesconclusionsusceptibility changes pml along gmwm junction can precede noticeable fluidattenuated inversion recovery flair changes correlates iron accumulation macrophages,0.0
hypothesis theory roles arginine methylation c9orf72mediated als ftd front cell neurosci 2021 mar 23 15633668 doi 103389 fncel2021633668 ecollection 2021abstracthexanucleotide repeat expansion g4c2n mutations gene c9orf72 account approximately 30 familial cases amyotrophic lateral sclerosis als frontotemporal dementia ftd well approximately 7 sporadic cases als g4c2n mutations known result production five species dipeptide repeat proteins drps noncanonical translation processes arginineenriched dipeptide repeat proteins glycinearginine polygr prolinearginine polypr demonstrated cytotoxic deleterious multiple experimental systems recently others implicated methylation polygr polypr arginine residues disease processes related g4c2n mutationmediated neurodegeneration previously reported inhibition asymmetric dimethylation adme arginine residues protective cellbased models polygr polypr cytotoxicity results consistent idea prmtmediated arginine methylation context polygr polypr exposure harmful however remains unclear discuss influence arginine methylation diverse cellular processes including liquidliquid phase separation chromatin remodeling transcription rna processing rnabinding protein localization consider methylation polygr polypr may disrupt processes essential normal cellular function survivalpmid33833668 pmcpmc8021787 doi103389 fncel2021633668,0.0
sgta associates intracellular aggregates neurodegenerative diseases abstractintracellular aggregates common pathological hallmark neurodegenerative diseases polyglutamine polyq diseases amyotrophic lateral sclerosis als parkinsons disease pd multiple system atrophy msa aggregates mainly formed aberrant diseasespecific proteins accompanied accumulation aggregateinteracting proteins although aggregateinteracting proteins considered modulate formation aggregates involved molecular mechanisms disease progression components aggregateinteracting proteins remain unknown study showed small glutaminerich tetratricopeptide repeatcontaining protein alfa sgta aggregateinteracting protein neurodegenerative diseases immunohistochemistry showed sgta interacted intracellular aggregates huntington disease hd cell models neurons hd model mice also revealed sgta colocalized intracellular aggregates postmortem brains patients polyq diseases including spinocerebellar ataxia sca 1 sca2 sca3 dentatorubralpallidoluysian atrophy addition sgta colocalized glial cytoplasmic inclusions brains msa patients whereas accumulation sgta observed neurons pd als patients vitro study showed sgta bound polyq aggregates cterminal domain sgta overexpression reduced intracellular aggregates results suggest sgta may play role formation aggregates may act potential modifier molecular pathological mechanisms polyq diseases msa,0.0
relationship neighborhood censustract level socioeconomic status respiratory syncytial virusassociated hospitalizations us adults 20152017 background respiratory syncytial virus rsv infection causes substantial morbidity mortality children adults socioeconomic status ses known influence many health outcomes studies relationship rsvassociated illness ses particularly adults understanding association important order identify address disparities prioritize resources preventionmethodsadults hospitalized laboratoryconfirmed rsv infection identified populationbased surveillance multiple sites us incidence rsvassociated hospitalizations calculated censustract ct poverty crowding adjusted age log binomial regression used evaluate association intensive care unit icu admission death ct poverty crowdingresultsamong 1713 cases rsvassociated hospitalization correlated increased ct level poverty crowding incidence rate rsvassociated hospitalization 258 ci 223 298 times higher cts highest compared lowest percentages individuals living poverty level 20 5 respectively incidence rate rsvassociated hospitalization 152 ci 133 173 times higher cts highest compared lowest levels crowding 5 1 households 1 occupant room respectively neither ct level poverty crowding correlation icu admission deathconclusionspoverty crowding ct level associated increased incidence rsvassociated hospitalization severe rsv disease efforts reduce incidence rsv disease consider ses,0.0
hn1l jpt2 signaling protein connects naadp generation ca2+ microdomain formation sci signal 2021 mar 23 14 675 eabd5647 doi 101126 scisignalabd5647abstractnaadpevoked ca2+ release type 1 ryanodine receptors ryr1 major mechanism underlying earliest signals t cell activation formation ca2+ microdomains characterization molecular machinery underlying naadp action identified naadpbinding protein called hematological neurological expressed 1like protein hn1l also known jupiter microtubuleassociated homolog 2 jpt2 gene deletion hn1l jpt2 human jurkat primary rat t cells resulted decreased numbers initial ca2+ microdomains delayed onset decreased amplitude global ca2+ signaling photoaffinity labeling demonstrated direct binding naadp recombinant hn1l jpt2 t cell receptor cd3dependent coprecipitation hn1l jpt2 ryrs colocalization proteins suggest hn1l jpt2 connects naadp formation activation ryr channels within first seconds t cell activation thus hn1l jpt2 enables naadp activate ca2+ release endoplasmic reticulum ryrpmid33758062 doi101126 scisignalabd5647,0.0
contribution gut microbiotabrain axis development brain disorders front neurosci 2021 mar 23 15616883 doi 103389 fnins2021616883 ecollection 2021abstractdifferent bacterial families colonize mucosal tissues human organism skin mouth vagina respiratory gastrointestinal districts particular mammalian intestine hosts microbial community 1 000 1 500 bacterial species collectively called microbiota cometabolism microbiota host system generated symbiotic relationship mutually beneficial balance achieved microbiota host organism fundamental organization immune system scientific studies highlighted direct correlation intestinal microbiota brain establishing existence gut microbiotabrain axis based theory microbiota acts development physiology cognitive functions brain although mechanisms involved yet fully interpreted similarly close relationship alteration intestinal microbiota onset several neurological pathologies highlighted review aims point current knowledge can found literature regarding connection intestinal dysbiosis onset particular neurological pathologies anxiety depression autism spectrum disorder multiple sclerosis disorders always considered consequence neuronal alteration review hypothesize alterations may nonneuronal origin consider idea composition microbiota directly involved direction following two key points will highlighted 1 direct crosstalk comes neurons gut microbiota 2 degree impact microbiota brain consider microbiota valuable target reducing modulating incidence certain neurological diseasespmid33833660 pmcpmc8021727 doi103389 fnins2021616883,0.0
interplay endocrine disruptors immunity implications diseases autoreactive etiology front pharmacol 2021 mar 23 12626107 doi 103389 fphar2021626107 ecollection 2021abstractthe sexbias disease susceptibility remained puzzling aspect several autoimmune conditions including postinfection viral autoimmunity last half twentieth century incidence rate femalebiased autoimmunity steadily increased independent medical advances suggested role environmental factors endocrine disrupting chemicals described interfere endocrine signaling endocrine involvement proper function innate adaptive immunity also defined however two areas rarely reviewed correlation addition studies addressing effects endocrine disruptors reported findings resulting broad range exposure doses schedules models experimental heterogeneity adds confusion may mislead translation findings human health work will normalize results across experiments provide necessary summary relevant human exposure novel approach describe different categories ubiquitously used environmental endocrine disruptors interfere immune relevant endocrine signaling contribute autoimmunity hope review will guide identification mechanisms concentrationdependent edc effects important sexbias autoimmunity also conditions immune dysfunction including postinfection autoreactivity may arise following severe acute respiratory syndrome coronavirus 2 epsteinbarr virus herpes simplex viruspmid33833678 pmcpmc8021784 doi103389 fphar2021626107,0.0
exploiting rational assembly map distinct roles regulatory cues autoimmune therapy acs nano 2021 mar 1 doi 101021 acsnano0c07440 online ahead printabstractautoimmune diseases like multiple sclerosis ms type 1 diabetes lupus occur immune system attacks host tissue immunotherapies promote selective tolerance without suppressing normal immune function tremendous interest nanotechnology used rational assembly peptides modulatory immune cues immune complexes complexes containing selfpeptides regulatory nucleic acids reverse established paralysis preclinical ms model importantly mice responding immunotherapy maintain healthy antigenspecific b t cell responses foreign antigen challenge therapeutic library isolating specific components reveals regulatory nucleic acids suppress inflammatory genes innate immune cells diseasematched peptide sequences control specificity tolerance distinct gene expression profiles cells animals associated immune signals administered particulate soluble forms highlighting impact biophysical presentation signals work provides insight rational manipulation immune signaling drive tolerancepmid33645967 doi101021 acsnano0c07440,0.0
tumor necrosis factor inhibition parkinson disease mendelian randomization study neurology 2021 feb 19101212 wnl0000000000011630 doi 101212 wnl0000000000011630 online ahead printabstractobjective evaluate effects longterm tumor necrosis factor tnf inhibition risk age onset parkinson disease pd performed twosample mendelian randomization study using genomewide association studies gwas summary statisticsmethods genetic variants vicinity tnfrsf1a gene encoding tnf receptor 1 tnfr1 identified predictive pharmacologic blockade tnfr1 signaling antitnf therapy based genetic associations lower circulating creactive protein crp gwas n 204 402 effects tnftnfr1 inhibition estimated pd risk ncases controls 37 688 981 372 age pd onset n 28 568 using gwas data international parkinsons disease genomics consortium 23andme inc validate variants proxies longterm antitnf treatment also assessed whether variant associations reflected anticipated effects tnfr1 inhibition crohn disease ulcerative colitis multiple sclerosis risk n 38 58945 975 results tnftnfr1 signaling inhibition estimated affect pd risk odds ratio per 10 lower circulating crp 099 95 ci 091108 age onset 013 years later onset 95 ci 066 092 contrast geneticallyindexed tnftnfr1 signaling blockade predicted reduced risk crohn disease 075 95 ci 065086 ulcerative colitis 084 95 ci 074097 increased multiple sclerosis risk 157 95 ci 136181 findings consistent across models using different genetic instruments mr estimatorsconclusions findings imply tnftnfr1 signaling inhibition will prevent delay pd onsetclassification evidence study provides class ii evidence tnftnfr1 signaling inhibition associated risk age onset pdpmid33608417 doi101212 wnl0000000000011630,0.0
atav comprehensive platform populationscale genomic analyses background common approach sequencing studies jointcalling store variants samples single file new samples continually added controls reused several studies cost time required perform jointcalling analysis can become prohibitiveresultswe present atav analysis platform largescale wholeexome wholegenome sequencing projects atav stores variant per site coverage data samples centralized database efficiently queried atav support diagnostic analyses trios singletons well rarevariant collapsing analyses finding disease associations complex diseases runtime logs ensure full reproducibility modularized atav framework makes extensible continuous development besides helping identification diseasecausing variants range diseases atav also enabled discovery diseasegenes rarevariant collapsing datasets containing 20 000 samples analyses date performed data 110 000 individuals demonstrating scalability frameworkto allow users easily access variantlevel data directly database provide webbased interface atav data browser http atavdborg browser summarylevel data 40 000 samples can queried general public representing mix cases controls diverse ancestries users access phenotype categories variant carriers well predicted ancestry gender quality metrics contrast many platforms data browser able show data newlyadded samples realtime therefore evolves rapidly samples sequencedconclusionsthrough atav users public access one largest variant databases patients sequenced tertiary care center can look genes variants interest additionally since entire code freely available github atav can easily deployed groups wish build platform database user interface,0.0
erythropoietin therapy case neonatal anemia exposure natalizumab throughout pregnancy background natalizumab monoclonal antibody approved treatment patients relapsingremitting multiple sclerosis according current clinical recommendations use pregnancy carefully evaluated women highly active disease plan pregnancy unplanned pregnancy accurate counseling eventual maternal disease relapse due therapy suspensioncase presentationthis brief case report describes case documented anemia observed newborn whose mother relapsingremitting multiple sclerosis treated extended dosing protocol natalizumab throughout pregnancy newborn received infusion erythropoietin every seven days fortieth day life subsequently status anemia underwent clinical resolutionconclusionsthis case report confirmed natalizumab can cause disorders hematopoiesis including anemia thrombocytopenia pancytopenia newborns patients treated pregnancy multidisciplinary team including experienced pediatricians pediatric hematologists critical role managing newborns delivered women treated natalizumab treating relapsingremitting multiple sclerosis pregnancy,0.0
highsalt diet suppresses autoimmune demyelination regulating bloodbrain barrier permeability proc natl acad sci u s 2021 mar 23 118 12 e2025944118 doi 101073 pnas2025944118abstractsodium chloride salt essential component daily food vitally contributes bodys homeostasis however excessive salt intake often held responsible numerous health risks associated cardiovascular system kidney recent reports linked highsalt diet hsd exacerbation artificially induced central nervous system cns autoimmune pathology changes microbiota enhanced th17 cell differentiation m kleinewietfeld et al nature 496 518522 2013 c wu et al nature 496 513517 2013 n wilck et al nature 551 585589 2017 however evidence dietary salt promotes worsens spontaneous autoimmune disease show hsd suppresses autoimmune disease development mouse model spontaneous cns autoimmunity found hsd consumption increased circulating serum levels glucocorticoid hormone corticosterone corticosterone enhanced expression tight junction molecules brain endothelial cells promoted tightening bloodbrain barrier bbb thereby controlling entry inflammatory t cells cns results demonstrate multifaceted potentially beneficial effects moderately increased salt consumption cns autoimmunitypmid33723078 doi101073 pnas2025944118,1.0
prolonging integrated stress response enhances cns remyelination inflammatory environment elife 2021 mar 23 10e65469 doi 107554 elife65469abstractthe inflammatory environment demyelinated lesions multiple sclerosis ms patients contributes remyelination failure inflammation activates cytoprotective pathway integrated stress response isr remains unclear whether enhancing isr can improve remyelination inflammatory environment examine possibility remyelination stage experimental autoimmune encephalomyelitis eae well mouse model incorporates cuprizoneinduced demyelination along cns delivery proinflammatory cytokine ifn used demonstrate either genetic pharmacological isr enhancement significantly increased number remyelinating oligodendrocytes remyelinated axons inflammatory lesions moreover combined treatment isr modulator sephin1 oligodendrocyte differentiation enhancing reagent bazedoxifene increased myelin thickness remyelinated axons prelesion levels taken together findings indicate prolonging isr protects remyelinating oligodendrocytes promotes remyelination presence inflammation suggesting isr enhancement may provide reparative benefit ms patientspmid33752802 doi107554 elife65469,1.0
cytoglmm conditional differential analysis flow mass cytometry experiments background flow mass cytometry important modern immunology tools measuring expression levels multiple proteins single cells goal better understand mechanisms responses single cell basis studying differential expression proteins current data analysis tools compare expressions across many computationally discovered cell types goal focus just one cell type narrower field application allows us define specific statistical model easier control statistical guaranteesresultsdifferential analysis marker expressions can difficult due marker correlations intersubject heterogeneity particularly studies human immunology address challenges two multiple regression strategies bootstrapped generalized linear model generalized linear mixed model simulated datasets compare robustness towards marker correlations heterogeneity strategies paired experiments find strategies maintain target false discovery rate medium correlations mixed models statistically powerful correct model specification unpaired experiments results indicate much larger patient sample sizes required detect differences illustrate cytoglmm r package workflow strategies pregnancy datasetconclusionour approach finding differential proteins flow mass cytometry data reduces biases arising marker correlations safeguards false discoveries induced patient heterogeneity,0.0
requirement protein geranylgeranylation chemokine receptor signaling th17 cell function animal model multiple sclerosis front immunol 2021 mar 22 12641188 doi 103389 fimmu2021641188 ecollection 2021abstractprecisely controlled lymphocyte migration critically required immune surveillance successful immune responses lymphocyte migration strictly regulated chemokines chemokine receptors show protein geranylgeranylation form posttranslational protein lipid modification required chemokine receptorproximal signaling mature thymocytes deficient protein geranylgeranylation impaired thymus egress circulating mature t cells lacking protein geranylgeranylation fail home secondary lymphoid organs transmigrate response chemokines vitro mechanistically protein geranylgeranylation modifies subunits heterotrimeric small gtpases essential chemokine receptor signaling addition protein geranylgeranylation also promotes differentiation il17producing t helper cells inhibiting differentiation foxp3+ regulatory t cells finally mice t cell lineagespecific deficiency protein geranylgeranylation resistant experimental autoimmune encephalomyelitis induction study elucidated critical role protein geranylgeranylation regulating t lymphocyte migration functionpmid33828552 pmcpmc8019753 doi103389 fimmu2021641188,0.0
impact covid19 patients neuromyelitis optica spectrum disorder beyond infection risk front neurol 2021 mar 22 12657037 doi 103389 fneur2021657037 ecollection 2021abstractthere increasing need better understanding impact coronavirus disease 2019 covid19 patients neuromyelitis optica spectrum disorder nmosd pilot studies investigated covid19 infections nmosd studies addressed disease activity immune status patients pandemic carried crosssectional study examine immune status relapses covid19 infections cohort nmosd patients using electronic patient registry msnmobase multiple sclerosis related disorders online questionnaire administered nmosd patients registry january 1 2011 june 1 2020 clinical demographic characteristics immune status relapses treatments covid19 infections preventive measures evaluated 752 registered patients 535 711 qualified data included total 486 used preventive therapies pandemic including mycophenolate mofetil 712 azathioprine 133 immunosuppressants 64 neither median immune cell counts immunoglobulin levels p 005 significantly different patients without immunosuppression pandemic patients diagnosed covid19 majority 95 took one effective protective measures eg wearing mask social distancing however significantly higher annualized relapse rate arr observed 33 patients treatment interruptions due pandemic compared p 005 whereas arr changes found patients continuous treatments without treatments p 005 interruption frequency significantly higher patients relapses compared without 349 vs 157 p 001 stable nmosd patients pandemic risk relapse due treatment interruption may higher risk covid19 infection protective measures used continuous relapseprevention treatments may necessarypmid33828524 pmcpmc8019749 doi103389 fneur2021657037,0.0
first norwegian doctorate multiple sclerosis tidsskr laegeforen 2021 mar 22 141 5 doi 104045 tidsskr200993 print 2021 mar 23no abstractpmid33754679 doi104045 tidsskr200993,0.0
successful treatment intubationinduced severe neurogenic postextubation dysphagia using pharyngeal electrical stimulation covid19 survivor case report background significant portion critically ill patients coronavirus disease 2019 covid19 high risk developing intensive care unit icu acquired swallowing dysfunction neurogenic dysphagia consequence requiring prolonged mechanical ventilation pharyngeal electrical stimulation pes simple safe treatment neurogenic dysphagia shown pes can restore safe swallowing orally intubated tracheotomized icu patients neurogenic dysphagia following severe stroke report case patient severe neurogenic postextubation dysphagia ped due prolonged intubation severe general muscle weakness related covid19 successfully treated using pescase presentationa 71yearold caucasian female patient confirmed severe acute respiratory syndrome coronavirus 2 sarscov2 infection developed neurogenic dysphagia following prolonged intubation icu avoid aerosolgenerating procedures swallowing function evaluated noninstrumentally recommended recently published international guidelines response covid19 pandemic swallowing function markedly impaired pes therapy recommended pes led rapid improvement ped evaluated bedside swallowing assessments using gugging swallowing screen guss dysphagia severity rating scale dsrs diet screening using functional oral intake scale fois improved swallowing reflected measures allowed patient transfer icu nonintensive medical department 5 days completing pes treatmentconclusionspes treatment contributed restoration safe swallowing function critically ill patient covid19 icuacquired swallowing dysfunction early clinical bedside swallowing assessment dysphagia intervention covid19 patients crucial optimize full recovery pes may contribute safe earlier icu discharge patients icuacquired swallowing dysfunction earlier icu discharge reduced rates reintubation following pes can help alleviate pressure icu bed capacity critical times health emergency ongoing covid19 pandemic,0.0
murine esophagus expresses glialderived central nervous system antigens int j mol sci 2021 mar 22 22 6 3233 doi 103390 ijms22063233abstractmultiple sclerosis ms considered specifically affect central nervous system cns long time autonomic dysfunction including dysphagia can occur accompanying phenomena patients enteric nervous system attracting increasing attention past years aim study identify glial myelin markers potential target structures autoimmune processes esophagus rtpcr analysis revealed glial fibrillary acidic protein gfap proteolipid protein plp myelin basic protein mbp expression absence myelin oligodendrocyte glycoprotein mog murine esophagus selected immunohistochemistry gfap plp mbp including transgenic mice celltype specific expression plp gfap supported results detection 1 gfap plp mbp schwann cells skeletal muscle esophagus 2 gfap plp mbp perisynaptic schwann cells skeletal esophageal motor endplates 3 gfap plp mbp glial cells surrounding esophageal myenteric neurons 4 plp gfap mbp enteric glial cells forming network esophagus results pave way investigations regarding involvement esophageal glial cells pathogenesis dysphagia mspmid33810144 doi103390 ijms22063233,1.0
nature genetic environmental susceptibility multiple sclerosis plos one 2021 mar 22 16 3 e0246157 doi 101371 journalpone0246157 ecollection 2021abstractobjective understand nature genetic environmental susceptibility multiple sclerosis ms extension susceptibility complex genetic diseasesbackground certain basic epidemiological parameters ms eg populationprevalence ms recurrencerisks ms siblings twins proportion women among ms patients timedependent changes sexratio wellestablished addition 233 geneticloci now identified unequivocally msassociated including 32 loci within major histocompatibility complex mhc one locus x chromosome despite recent explosion genetic associations however association ms hladrb11501hladqb10602a1 h+ haplotype known decadesdesign methods define geneticallysusceptible subset g include everyone nonzero lifetime chance developing ms individuals chance developing ms regardless environmental experiences belong mutually exclusive nonsusceptible subset g using wellestablished epidemiological parameters analyze mathematically implications observations regarding geneticsusceptibility ms addition use sexratio change observed 35year interval canada derive relationship msprobability increasing likelihood sufficient environmental exposureresults demonstrate geneticsusceptibitly confined less 73 populations throughout europe north america consequently 927 individuals populations chance whatsoever developing ms regardless environmental experiences even among carriers hladrb11501hladqb10602a1 haplotype far fewer 32 can possibly members g subset also despite current preponderance women among ms patients women less likely susceptible g subset higher environmental threshold developing ms compared men nevertheless penetrance ms susceptible women considerably greater men moreover responsecurves msprobability susceptible individuals increases increasing likelihood sufficient environmental exposure especially among women however environmental responsecurves plateau 50 women significantly lower level menconclusions pathogenesis ms requires genetic predisposition suitable environmental exposure nevertheless geneticsusceptibility rare population 73 requires specific combinations nonadditive genetic riskfactors example minority carriers hladrb11501hladqb10602a1 haplotype even g subset thus geneticsusceptibility ms carriers must result combined effect haplotype together effects certain yet unidentified genetic factors haplotype poses msrisk contrast sufficient environmental exposure however many events involved whenever events need act whatever events might common currently occurring least 76 susceptible individuals addition fact environmental responsecurves plateau well 50 especially men indicates disease pathogenesis partly stochastic extension diseases monozygotictwin recurrencerisks greatly exceed diseaseprevalence eg rheumatoid arthritis diabetes celiac disease must similar genetic basispmid33750973 doi101371 journalpone0246157,0.0
usability fall risk mhealth app people multiple sclerosis mixed methods study jmir hum factors 2021 mar 22 8 1 e25604 doi 102196 25604abstractbackground multiple sclerosis ms chronic neurodegenerative disease causes range motor sensory cognitive symptoms due symptoms people ms high risk falls fallrelated injuries reductions quality life cure ms managing symptoms disease progression important maintain high quality life mobile health mhealth apps commonly used people ms help manage health however limited health apps people ms designed evaluate fall risk fall risk app can increase access fall risk assessments improve selfmanagement designing mhealth apps usercentered approach critical improving use adoptionobjective purpose study undergo usercentered approach test refine usability app iterative design processmethods fall risk app steadyms extension steady fall risk app older adults steadyms consists 2 components 25item questionnaire demographics ms symptoms 5 standing balance tasks data questionnaire balance tasks inputted algorithm compute fall risk score two iterations semistructured interviews n5 participants per iteration performed evaluate usability people ms used steadyms smartphone thinking loud interviews recorded transcribed developed codes themes people ms also completed system usability scaleresults total 3 themes identified intuitive navigation efficiency use perceived value overall participants found steadyms efficient use useful learn fall risk score challenges related cognitive overload balance tasks modifications made second iteration people ms reported app intuitive efficient average system usability scale scores 955 iterations representing excellent usabilityconclusions steadyms first mhealth app people ms assess overall risk falling usable subset people ms people ms found steadyms usable useful understanding risk falling developing future mhealth apps people ms important prevent cognitive overload simple clear instructions present scores understood interpreted correctly visuals text findings underscore importance usercentered design provide foundation future development tools assess prevent scalable falls people ms future steps include understanding validity fall risk algorithm evaluating clinical utility apppmid33749609 doi102196 25604,0.0
development registry data create interactive doctorpatient platforms personalized patient care taking example destiny system front digit health 2021 mar 22 3633427 doi 103389 fdgth2021633427 ecollection 2021abstractrealworld evidence rwe becoming increasingly important order integrate results randomized studies everyday clinical practice data collection rwe usually derived largescale national international registries often driven academic centers developed digitalized doctorpatient platform called destiny databaseassisted therapy decision support system utilized neurotransdata ntd network neurologists psychiatrists throughout germany platform can integrated everyday practice well used scientific evaluations healthcare research can also serve individual personalized treatment application various modules allow timely identification sideeffects interactions treatments can involve patients via ntc health guide portal can collect data individual disease histories integrated innovative algorithms eg prediction treatment response currently available multiple sclerosis ms indications pipeline describe doctorpatient platform destiny outpatient neurological practices contribution improved treatment success well reduction healthcare costs platforms like destiny may facilitate goal personalized healthcarepmid34713104 pmcpmc8521878 doi103389 fdgth2021633427,0.0
dietinduced obesity leads behavioral indicators pain preceding structural joint damage wildtype mice abstractintroductionobesity one largest modifiable risk factors development musculoskeletal diseases including intervertebral disc ivd degeneration back pain despite clinical association studies directly assessed whether dietinduced obesity accelerates ivd degeneration back pain investigated biological mediators underlying association study examine effects chronic consumption highfat highfat highsugar western diet ivd knee joint painassociated outcomesmethodsmale c57bl 6n mice randomized one three diet groups chow control highfat highfat highsugar western diet 10 weeks age remained diet 12 24 40 weeks endpoint animals assessed behavioral indicators pain joint tissues collected histological molecular analysis serum collected assess markers systemic inflammation iba1 gfap cgrp measured spinal cords immunohistochemistryresultsanimals fed obesogenic highfat western diets showed behavioral indicators pain beginning 12 weeks persisting 40 weeks diet consumption histological indicators moderate joint degeneration detected ivd knee following 40 weeks experimental diets mice fed obesogenic diets showed synovitis increased intradiscal expression inflammatory cytokines circulating levels mcp1 compared control linear regression modeling demonstrated age diet significant predictors painrelated behavioral outcomes histopathological joint degeneration synovitis associated alterations spontaneous activityconclusiondietinduced obesity accelerates ivd degeneration knee oa mice however painrelated behaviors precede independent histopathological structural damage findings contribute understanding source obesityrelated back pain contribution structural ivd degeneration,0.0
immune response aging chronic inflammatory demyelinating polyradiculoneuropathy abstractchronic inflammatory demyelinating polyradiculoneuropathy cidp consists various autoimmune subtypes peripheral nervous system pns attacked cidp can follow relapsingremitting progressive course resultant demyelination caused immune cells eg t cells macrophages antibodies can lead disability patients importantly age cidp patients role symptomology specific variants associated differing ages onset furthermore older patients decreased frequency functional recovery cidp insult may related perturbations immune cell populations exacerbate disease increasing age present review immune profile typical cidp will discussed followed inferences potential role relevant aging immune cell populations atypical variants will also briefly reviewed followed examination available studies immunology underlying,1.0
drugs multiple sclerosis med lett drugs ther 2021 mar 22 63 1620 4248no abstractpmid33976089,0.0
antigenspecific immune tolerance multiple sclerosispromising approaches bring patients front immunol 2021 mar 22 12640935 doi 103389 fimmu2021640935 ecollection 2021abstractantigenspecific tolerance induction aims treating multiple sclerosis ms root pathogenesis prospect personalization several promising tolerization approaches using different technologies modes action already advanced clinical testing prerequisites successful tolerance induction include knowledge target antigens core pathomechanisms pursue clinical development path distinct conventional drug development key aspects including patient selection outcome measures demonstrating mechanisms action well positioning rapidly growing spectrum ms treatments considered bring therapy patientspmid33828551 pmcpmc8019937 doi103389 fimmu2021640935,0.0
accurate monitoring response bone metastases treatment patients prostate cancer using choline pet ct case rep oncol 2021 mar 22 14 1 520524 doi 101159 000514191 ecollection 2021 janaprabstractwe report 2 cases castrationresistant prostate cancer crpc observed two times 11ccholine positron emission tomography computed tomography pet ct useful discriminate viable progressive osteoblastic bone metastasis benign osteoblastic change induced treatment effect determine viability bone metastases regardless whether sclerosis present one case demonstrated disappearance abnormal 11ccholine uptake osteoblastic metastatic lesions abiraterone therapy new lesions sites suggesting nonviable bone metastases can assume complete metabolic response case demonstrated decrease existing abnormal 11ccholine uptake osteoblastic metastatic lesions multiple new appearances osteoblastic nonosteoblastic lesions abnormal 11ccholine uptake radium223 therapy suggesting multiple viable bone metastases can assume progressive metabolic disease 11ccholine pet ct help assessing treatment response bone metastases patients metastatic crpcpmid33976628 pmcpmc8077372 doi101159 000514191,0.0
inhibition tlr4 signaling protects mice sensory motor dysfunction animal model autoimmune peripheral neuropathy background etiology remains elusive macrophages t cells peripheral nerves considered effector cells mediating autoimmune peripheral neuropathy apn guillainbarre syndrome recognizing pathogenassociated molecular patterns pamps damageassociated molecular patterns damps signals tlrs play central role initiation innate adaptive immune responses study aimed understand involvement tlr4 pathogenesis apn explore potential tlr4 drug target therapeutic usemethodsapn induced partial ligation one sciatic nerves b72 l31 transgenic mice possess predisposed inflammatory background apn pathology neurological function evaluated noninjured sciatic nerveresultstlr4 endogenous ligand hmgb1 highly expressed l31 mice circulating immune cells peripheral nerves enhanced tlr4 signaling blocked tak 242 selective tlr4 inhibitor disease onset intraperitoneal administration tak 242 inhibited monocyte macrophage cd8+ t cell activation also reduced release proinflammatory cytokines tak 242 protected mice severe myelin axonal loss resulting remarkable improvement mouse motor sensory functions tak 242 effective alleviating disease preventive reversal paradigmsconclusionthe study identified critical contribution tlr4mediated macrophage activation disease course provided strong evidence support tlr4 useful drug target treating inflammatory autoimmune neuropathy,1.0
efficacy probiotics multiple sclerosis systematic review preclinical trials metaanalysis randomized controlled trials food funct 2021 feb 25 doi 101039 d0fo03203d online ahead printabstractpreliminary evidence shows potential role probiotics ameliorating multiple sclerosis ms however effects probiotics ms remain unclear therefore aim study evaluate efficacy probiotics multiple sclerosis systematically reviewing preclinical trials animal trials performing metaanalysis randomized controlled trials pubmed web science cochrane central randomized clinical trials embase clinical trials search engine google scholar systematically searched manually screened updated november 2020 resulting eligible 3 randomized controlled trials rcts 22 preclinical studies metaanalysis rcts enrolling 173 patients ms receiving probiotics revealed significant beneficial effects probiotic supplementation mental health expanded disability status scale scores standardized mean difference smd 122 i2 92 95 ci 240 003 p 004 beck depression inventory total scores smd 158 i2 94 95 ci 303 012 p 003 general health questionnaire scores smd 071 i2 0 95 ci 102 040 p 000001 depression anxiety stress scale scores smd 072 i2 0 95 ci 112 033 p 00003 low certainty evidence addition probiotic intake markedly improved insulin resistance inflammatory oxidative stress markers preclinical studies shown probiotic consumption reduces incidence severity ms delays ms progression 15 studies improves motor impairment 3 studies favorable alterations immune inflammatory markers 20 studies intestinal microbiome compositions 4 studies ms results indicated probiotics may beneficial effects prevention treatment multiple sclerosispmid33629669 doi101039 d0fo03203d,0.0
clinical false positives resulting recent intravenous immunoglobulin therapy case report background many clinicians aware certain therapies administered patients can downstream consequences form clinical laboratory test interferences particularly true laboratory tests depend directly involve use antibodybased methodology intravenouslyadministered immunoglobulin therapy one treatment can theory directly impact results particular tests area viral serology study can help serve reference clinicians researching impact intravenouslyadministered immunoglobulin therapy context positive results reflect clinical background patientcase presentationwe describe case whereby intravenouslyadministered immunoglobulin therapy led series clinical false positives viral serology inconsistent known patient history well recent laboratory results patient presented hospital petechiaetype bleeding rashes investigated thrombocytopenia initial blood investigations indicated low plateletssubsequent testing potential causes lowplatelet involved several viral serology investigations including hepatitis cytomegalovirus human immunodeficiency virus initial testing indicated patient exhibited negative status viral antibodies antigens except immunity hepatitis b surface antigen antibody part thrombocytopenia treatment intravenouslyadministered immunoglobulin therapy administered subsequent viral serology ordered investigations indicated positive status several hepatitis antibodies well cytomegalovirusconclusionsthis case study illustrates potential improper diagnosis previous ongoing infection status patients administered ivig therapy caution exercised particularly interpreting results involving cytomegalovirus hepatitis,0.0
roberto melaragno scientific contributions brazilian neurology roberto melaragno filho associate professor neurology school medicine universidade de paulo head neurology service hospital servidor pblico estadual francisco morato oliveira hspefmo significant scientific career recognized reference 20th century brazilian neurology addition notable international career,0.0
prevalence multiple sclerosis key cities brazil study joinville southern brazil abstract background brazilian committee treatment research multiple sclerosis bctrims launched initiative determine prevalence multiple sclerosis ms brazil based key cities deemed representative regions terms demographic environmental features objective investigate prevalence rate ms joinville methods reviewed medical records patients lived joinville met 2010 mcdonalds diagnostic criteria revised ms prevalence day march 11 2016 potential ms patients included individuals treated practicing neurologists city ones found patients association database municipal department health advertisements survey also broadcast radio television patients living joinville prevalence day excluded potential ms patients invited inperson diagnostic review carried panel experienced neurologists special expertise ms march 11 2016 results ms prevalence rate 135 per 100 000 inhabitants 95 confidence interval 95ci 129140 100 000 total 51 662 participants females 26 337 males female male ratio191 77 patients 73 948 caucasians four 51 mixedrace conclusions despite latitude location european colonization prevalence rate expectation intense internal migration regions lower ms prevalence rates joinville may played role attenuating increased risk ms associated latitude gradient european ancestry prevalence studies cities southern brazil significant internal migration taking part broad project may clarify issue,0.0
alphalipoic acid supplementation increases efficacy exercise dietinduced obesity treatment induces immunometabolic changes female mice women abstractthe decrease regulatory t cells tregs population highly involved adipose tissue inflammation insulin resistance obesity tregs depend fatty acids via oxidation immunosuppressive function adapting antioxidant systems allow survival oxidative stress study hypothesized dietary supplementation alphalipoic acid ala powerful antioxidant improve immunometabolism added classical strategy obesity treatment first showed vitro experiments ala favors polarization mice cd4+t cells toward tregs next carried translational study female obese mice women supplemented ala vehicle placebo mice 25 gala kgfood 6weeks women 600 mgala day 8weeks following protocol including regular exercise change diet fatty acid oxidation potential activity nuclear erythroidrelated factor 2 nrf2 mouse secondary lymphoid tissues improved ala supplementation ala reduced visceral adipose tissue vat mass preserved tregs vat mice women ala supplementation induced significant metabolic changes circulating cd4+t cells including increased oxidative capacity fatty acid oxidation ameliorated redox status improved reduction visceral fat mass appropriate biological markers still required used clinics judge effectiveness longterm obesity treatment studies female mice women needed determine whether immunometabolic changes reduce vat massassociated risk secondary health issues arising obesity,0.0
targeting chemokines acute lymphoblastic leukemia therapy abstractacute lymphoblastic leukemia hematological malignancy characterized malignant clonal expansion lymphoid hematopoietic precursors regulated various signaling molecules cytokines adhesion molecules microenvironment chemokines chemotactic cytokines regulate migration positioning interactions cells many chemokine axes cxcl12 cxcr4 ccl25 ccr9 proved play important roles leukemia microenvironment affect outcomes review summarize chemokines involved progression elaborate roles mechanisms leukemia cell proliferation infiltration drug resistance disease relapse also discuss potential targeting chemokine axes treatments since many related inhibitors shown promising efficacy preclinical trials entered clinical trials,0.0
healthrelated quality life multiple sclerosis patients european multicountry study background inconsistent use generic diseasespecific healthrelated quality life hrqol instruments multiple sclerosis ms studies limits crosscountry comparability objectives 1 investigate realworld hrqol ms patients using generic diseasespecific hrqol instruments netherlands france united kingdom spain germany italy 2 compare hrqol among countries 3 determine factors associated hrqolmethodsa crosssectional observational online webbased survey amongst ms patients conducted juneoctober 2019 patient demographics clinical characteristics two hrqol instruments generic euroqol eq5d5l diseaserelated multiple sclerosis quality life msqol 54 extension generic short form36 sf36 collected health utility scores calculated using countryspecific value sets mean differences hrqol analysed predictors hrqol explored regression analysesresultsin total 182 patients included netherlands n 88 france n 58 united kingdom n 15 spain n 10 living elsewhere n 11 mean msqol54 physical mental composite scores 425 sd172 583 sd215 lower whereas sf36 physical mental composite scores 468 sd226 531 sd225 higher reported previous clinical trials mean eq5d utility 065 sd026 crosscountry differences hrqol found common predictor hrqol disability status primary progressive msconclusionsthe effects ms hrqol realworld patients may underestimated combined use generic diseasespecific hrqol instruments enhance understanding health needs ms patients consequent use instruments clinical trials observational studies improves crosscountry comparability hrqol,0.0
early behavioral physiological markers social anxiety infants fragile x syndrome background social anxiety highly prevalent neurotypical children children fragile x syndrome fxs fxs genetic syndrome characterized intellectual disability increased risk autism spectrum disorder social anxiety left untreated negative outcomes highly prevalent later life however early detection social anxiety challenging symptoms often subtle absent early life given prevalence impairment associated childhood social anxiety efforts accelerated identify risk markers anxiety cluster early features anxiety identified including elevated behavioral inhibition attentional biases physiological dysregulation index early emerging markers social anxiety infants fxs provide unique opportunity study earlier predictors social anxiety current study utilized multimethod approach investigate early markers social anxiety 12monthold infants fxsmethodparticipants included 32 infants fxs 41 lowrisk controls approximately 12 months old parentreported social behavioral inhibition recorded infant behavior questionnaire ibqr direct observations behavioral inhibition attention measured stranger approach task respiratory sinus arrhythmia collected simultaneouslyresultsparentreported social behavioral inhibition significantly different groups contrast direct observations suggested infants fxs displayed elevated behavioral inhibition increased attention towards stranger blunted respiratory sinus arrhythmia responseconclusionsfindings suggest infants fxs show behavioral physiological markers social anxiety 12 months old using biobehavioral approach multiple sources input results highlight importance multimethod approach understanding complex early emergent characteristics anxiety infants fxs,0.0
catastrophic outofpocket health expenditure multiple sclerosis patients iran background present study designed conducted evaluate multiple sclerosis ms treatment costs resulting economic impact imposed ms patients iranmethodsthis crosssectional study among randomly selected 300 ms patients registered ms association east azerbaijan province iran 1 year treatment began regression analysis anova ttest chisquare usedresultsthe average amount outofpocket payments oops ms patients previous year 166920 usd spent medication rehabilitation care physician visits mean annual income 518284 usd fifty four percent families ms patient suffer catastrophic health expenditure che 44 experience poverty caused oops occupational status supplemental health insurance residents tabriz significantly affect oops che resulting poverty p 005 conclusionthe catastrophic financial burden health care costs ms patients families justifies health policymakers promote prepayment systems provide subsidies less welloff patients protect unfairness oops resulting che poverty,0.0
neural crest cellderived pericytes act proangiogenic cells human neocortex development gliomas abstractcentral nervous system diseases involving parenchymal microvessels frequently associated microvasculopathy includes different levels neurovascular unit nvu dysfunction including bloodbrain barrier alterations contribute understanding nvu responses pathological noxae focused one cellular components microvascular pericytes highlighting unique features brain pericytes aid analyses carried vascularization human developing neocortex human gliomas thanks position centred within endothelial glial partition vessel basal lamina therefore inserted endothelial cells perivascular vesselassociated components astrocytes oligodendrocyte precursor cells opcs ng2glia microglia macrophages nerve terminals pericytes fulfil central role within microvessel nvu indeed critical site pericytes number direct extracellular matrix molecule soluble factormediated functions displaying marked phenotypical functional heterogeneity carrying multitasking services pericytes heterogeneity primarily linked position specific tissue organ microenvironments importantly ontogeny ontogenesis pericyte subtypes belong two main embryonic germ layers mesoderm neuro ectoderm therefore expected found organs ontogenetically different nonetheless pericytes different origin may converge colonize neighbouring areas organ apparatus provide brief overview unusual roles played forebrain pericytes processes angiogenesis barriergenesis virtue origin midbrain neural crest stem cells better knowledge ontogenetic subpopulations may support understanding specific interactions mechanisms involved pericyte function dysfunction including normal pathological angiogenesis thereby offering alternative perspective cell subtypespecific therapeutic approaches,0.0
chasing dragon fatal case report toxic leucoencphalopathie due inhaled heroin leukoencephalopathy myelin disorder caused multiple agents including substance abuse 28yearold man arrived emergency department suffered asthenia dizziness disorientation ataxia two months twoyear history heroin inhalation arrived normal physical condition brain magnetic resonance showed bilateral diffuse hypointense lesions white matter day 3 admission presented neurological deterioration stupor haemodynamic instability respiratory failure died toxic leukoencephalopathy symptoms start inattention memory personality changes may eventually cause dementia death heroin inhalation common practice can lead leukoencephalopathy leukoencephalopathy associated heroin inhalation rare entity mainly affects young adults high social impact aetiology unclear effective treatment high mortality rate heroin consumption rise colombia tl considered medical staff,1.0
espasticidad spasticity motor disorder forms part upper motor neuron syndrome characterized speeddependent increase tonic stretch reflex muscle tone frequently seen patients upper motor neuron syndrome secondary various pathologies cerebrovascular attacks spinal cord injuries multiple sclerosis cerebral palsy multidisciplinary individualized approach essential treatment patients includes nonpharmacological pharmacological neurosurgical orthopedic management present paper intends carry updated nonsystematic review history epidemiology pathophysiology diagnosis therapeutic approach spasticity adult pediatric population well proposing therapeutic algorithm,1.0
giant intrapericardial bronchogenic cyst associated congestive heart failure atrial fibrillation case report background large intracardiac bronchogenic cysts rare mediastinal masses however must always considered differential diagnosis heart failure abnormal chest xraycase presentationwe present 60yearold female patient de novo atrial fibrillation heart failure large intrapericardial mass patient underwent successful surgical resection pathological findings confirming bronchogenic cystconclusionslarge bronchogenic cysts located intrapericardially rare however included differential diagnosis patients presenting atrial fibrillation heart failure abnormal radiologic studies,0.0
peginterferon beta1a associated high adherence satisfaction patients multiple sclerosis german realworld study ther adv neurol disord 2021 mar 19 1417562864211000461 doi 101177 17562864211000461 ecollection 2021abstractbackground peginterferon beta1a developed treatment relapsingremitting multiple sclerosis rrms provide interferon increased exposure facilitate adherence reducing frequency application noninterventional observational study investigated adherence peginterferon beta1a realworld clinical practice settingsmethods prospective study conducted 1 2015 1 2018 77 german ms sites adult patients rrms previously treated treatmentnave receiving peginterferon beta1a 125 g sc every 2 weeks eligible participation data documented every 3 months 2 years nine visits primary endpoint percentage patients overall adherence defined 10 injections administered throughout 24month observation period secondary endpoints included persistence patient satisfaction efficacy relapse activity disability progression tolerability patients invited participate individualised patient support programmeresults 250 enrolled patients 190 aged 1874 years 753 female included efficacy analysis 74 patients completed study 332 treatmentnave proportion patients overall adherence 90 757 95 ci 679816 annualised relapse rate 017 compared previous therapies scores treatment satisfaction convenience markedly higher peginterferon beta1a overall 874 participated patient support programme 478 patients reported adverse eventsconclusions adherence biweekly treatment peginterferon beta1a high although adherence positively influenced wellaccepted patient support programme extent unequivocally evaluated clinical disease activity remained low peginterferon beta1a well tolerated new relevant safety findingspmid33796146 pmcpmc7983429 doi101177 17562864211000461,0.0
narrative review ethnomedicinal usage cannabis sativa linnaeus traditional phytomedicine folk medicine practitioners bangladesh background worldwide interest use cannabis sativa biomedicine purposes cannabis ethnomedicinal usage natural medicine bangladesh cultivated british empire period revenuesobjectivefolk medicine practitioners fmps different districts bangladesh using cannabis sativa now compiled studies particularly regarding practice hence review effort retrieve traditional usage cannabis sativa phytomedicine published ethnomedicinal studiesmethods materialsinformation searched using search terms ethnomedicinal cannabis sativa bangladesh bangladesh cannabaceae ethnomedicinal survey ganja bhang folk medicine bangladesh tetrahydrocannabinol thc cannabinoid therapeutic clinical trial cannabis pharmacological biological retrieved ethnobotanical articles available pubmed scopus science direct google scholar databases search relevant scientific literature also conducted assess efficacy ethnomedicinal usage cannabis sativaresultswhile reviewing 200 ethnomedicinal plants survey articles found fmps bangladesh 12 different districts used cannabis sativa treat cited ailments like sleepassociated problems n5 neuropsychiatric cns problems n5 infections respiratory problems n5 followed rheumatism gastrointestinal gynecological n4 cancer sexual ailments including hypertension headache itch increases bile secretion abortifacient dandruff fever urinary problems n1 total 15 formulations identified 11 18 ethnomedicinal plant survey reports leaf main plant part used 538 followed root 23 seed 77 flower inflorescence resin parts 38 respectivelyconclusionssales cultivation cannabis illegal present bangladesh use cannabis sativa natural phytomedicine practiced traditionally folk medicine practitioners bangladesh many years validated relevant pharmacological justification although cannabis sativa possesses ethnomedicinal properties folk medicine bangladesh furthermore needed conduct biological research consolidate pharmacological justification prospects challenges cannabis cannabinoids use bangladesh safer biomedicine future,0.0
improved gastrointestinal profile diroximel fumarate associated positive impact quality life compared dimethyl fumarate results randomized doubleblind phase iii evolvems2 study ther adv neurol disord 2021 mar 19 141756286421993999 doi 101177 1756286421993999 ecollection 2021abstractbackground diroximel fumarate drf novel oral fumarate approved relapsing forms multiple sclerosis ms drf demonstrated significantly improved gastrointestinal gi tolerability versus dimethyl fumarate dmf fewer days individual gastrointestinal symptom impact scale igisis scores 2 gi adverse events aes treatment discontinuations due gi aes aim evaluate impact gi tolerability events quality life qol patients relapsingremitting ms received drf dmf evolvems2methods post hoc analysis conducted patients enrolled randomized blinded 5week evolvems2 clinicaltrialsgov identifier nct03093324 study drf versus dmf patients completed daily igisis global gisis ggisis ediary questionnaires assess gi symptom intensity interference daily activities workresults total 504 patients drf n 253 dmf n 251 received study drug 502 drf n 253 dmf n 249 completed least one postbaseline questionnaire drf gi symptoms less likely interfere quite bit extremely regular daily activities igisis drf 95 24 253 versus dmf 289 72 249 work productivity ggisis drf 61 10 165 versus dmf 113 18 159 drftreated patients fewer days 1 h missed work drf 43 days n 20 versus dmf 88 days n 26 dmftreated patients reported highest gi symptom severity missed work week 23 shortly completing titration period coincided majority girelated treatment discontinuations 583 7 12 gi tolerability aes drf 348 88 253 dmf 482 121 251 concomitant symptomatic medication use drf 193 17 88 versus dmf 306 37 121 girelated discontinuations drf 08 versus dmf 48 lower drf versus dmfconclusions improved gi tolerability drf translated clinically meaningful benefits qol patients experienced less impact daily life work required less concomitant symptomatic medication usetrial registration clinicaltrialsgov identifier nct03093324 pmid33796143 pmcpmc7985943 doi101177 1756286421993999,0.0
qigong mindbody program caregivers cancer patients design pilot threearm randomized clinical trial background informal caregivers often family friends experience significant psychological physical distress leading reductions health quality life qol mindbody interventions focused caregivers often limited address multiple barriers including caregivers economic geographic time constraints translation inperson communitybased interventions internetbased delivery may offer greater accessibility caregivers leading increased adherencemethodscaring caregivers mindbody implements threearm pilot randomized controlled trial evaluate feasibility delivering qigong intervention eight brocades cancer caregivers total 54 cancer caregivers will randomized one three 12week programs 1 communitybased qigong 2 internetbased qigong 3 selfcare control group studyspecific aims include 1 modify intervention content online delivery 2 evaluate feasibility recruiting retaining cancer caregivers 12week clinical trial 3 evaluate feasibility collecting managing data suitability questionnaires population several outcomes will assessed including caregiver qol caregiver burden caregiver distress perceived social support physical function cognitive function 6month followup will also assess longerterm changes qol psychosocial wellbeingdiscussionfindings will used inform design conduct largescale comparative effectiveness trial evaluating caregivers received qigong training delivered communitybased vs internetbased programs finding either programs effective inform care options caregiverstrial registrationnct04019301 registered july 15 2019 clinicaltrialsgov,0.0
enhanced insulin signalling ameliorates c9orf72 hexanucleotide repeat expansion toxicity drosophila elife 2021 mar 19 10e58565 doi 107554 elife58565 online ahead printabstractg4c2 repeat expansions within c9orf72 gene common genetic cause amyotrophic lateral sclerosis als frontotemporal dementia ftd repeats undergo repeatassociated nonatg translation generate toxic dipeptide repeat proteins show insulin igf signalling reduced fly models c9orf72 repeat expansion using rnasequencing adult brain demonstrate activation insulin igf signalling can mitigate multiple neurodegenerative phenotypes flies expressing either expanded g4c2 repeats toxic dipeptide repeat protein polygr levels polygr reduced components insulin igf signalling pathway genetically activated diseased flies suggesting mechanism rescue modulating insulin signalling mammalian cells also lowers polygr levels remarkably systemic injection insulin improves survival flies expressing g4c2 repeats overall data suggest modulation insulin igf signalling effective therapeutic approach c9orf72 als ftdpmid33739284 doi107554 elife58565,0.0
nuclear lamina invaginations pathological feature c9orf72 als ftd abstractthe common genetic cause familial sporadic amyotrophic lateral sclerosis als ggggcc hexanucleotide repeat expansion hre c9orf72 gene direct molecular hallmarks c9orf72 hre repeat rna foci dipeptide repeat protein pathology well characterized mechanisms c9orf72 hre causes als related neurodegenerative disease frontotemporal dementia ftd remain poorly understood recently alterations nuclear pore complex nucleocytoplasmic transport accepted prominent pathomechanism underlying c9orf72 als ftd however global disruptions nuclear morphology nuclear lamina remain controversial use large number induced pluripotent stem cell derived spinal neurons postmortem human motor cortex sections thoroughly examine nuclear morphology nuclear lamina disruptions light microscopy contrast previous studies artificial overexpression model systems endogenous levels c9orf72 hre increase frequency nuclear lamina invaginations addition c9orf72 hre impact overall nuclear shape size notably frequency nuclear lamin b1 invaginations increases cellular aging independent c9orf72 hre together data suggest nuclear morphology unaltered c9orf72 als ftd,0.0
mice heterozygous sodium channel scn8a nav16 reduced inflammatory responses eae following lps challenge front immunol 2021 mar 19 12533423 doi 103389 fimmu2021533423 ecollection 2021abstractvoltage gated sodium nav channels contribute axonal damage following demyelination experimental autoimmune encephalomyelitis eae rodent model multiple sclerosis ms nav16 isoform implicated primary contributor process however role nav16 immune processes critical pathology ms eae extensively studied eae induced myelin oligodendrocyte mog3555 peptide scn8admu + mice reduced nav16 levels scn8admu + mice demonstrated improved motor capacity recovery early chronic phases eae relative wildtype animals optic nerve myeloid cell infiltration effects eae axonal ultrastructure also significantly reduced scn8admu + mice analysis innate immune parameters revealed reduced plasma il6 levels decreased percentages gr1high cd11b+ gr1int cd11b+ myeloid cells blood chronic phase eae scn8admu + mice elevated levels antiinflammatory cytokines il10 il13 tgf1 also observed brains untreated scn8admu + mice lipopolysaccharide lps model used evaluate inflammatory responses scn8admu + mice displayed reduced inflammation response lps challenge evaluate immune cellintrinsic difference result changes immune hormonal environment mast cells derived bone marrow scn8admu + mice mast cells also produced lower levels il6 response lps compared wild type mice results demonstrate addition recognized impact axonal damage nav16 impacts multiple aspects innate inflammatory responsepmid33815353 pmcpmc8017164 doi103389 fimmu2021533423,1.0
switching treatments clinically stable relapsing remitting multiple sclerosis patients planning pregnancy mult scler j exp transl clin 2021 mar 19 7 1 20552173211001571 doi 101177 20552173211001571 ecollection 2021 janmarabstractbackground decision children can complex particularly people multiple sclerosis ms key concern use disease modifying drugs dmds pregnancy continuing stopping switching may affect mother child people active ms stopping medications puts mother risk relapse disease reboundobjectives review evidence effect different switching strategies people stable relapsing remitting ms rrms methods searched medline embase emcare cinahl scopus cochrane library march 2020 papers english included limits applied seven articles included four cohorts two case reports one randomized controlled trial rct results two strategies found deescalating associated increased risk relapses switching first line injectables change relapse rate observedconclusion evidence effect switching strategy disease course stable rrms patients planning pregnancy scarce switching current evidence suggests risk relapses mirrors known medication efficacypmid33796332 pmcpmc7985951 doi101177 20552173211001571,0.0
adiposederived mesenchymal stem cells attenuate dialysisinduced peritoneal fibrosis modulating macrophage polarization via interleukin6 background lifelong peritoneal dialysis pd renal replacement therapy limited peritoneal fibrosis previous studies showed immunomodulatory antifibrotic effects adiposederived mesenchymal stem cells adscs peritoneal fibrosis however role peritoneal macrophage process remains uninvestigatedmethodswe examined therapeutic effects adsc bone marrowderived mesenchymal stem cells bmmsc rat model dialysisinduced peritoneal fibrosis using methylglyoxal addition treatment macrophages conditioned medium adsc bmmsc performed individually identify beneficial component stem cell secretomeresultsin vivo experiments found dialysisinduced rat peritoneal fibrosis attenuated adsc bmmsc interestingly adsc possessed prominent therapeutic effect bmmsc ameliorating peritoneal membrane thickening also upregulating epithelial cell markers rat peritoneal tissues therapeutic effects adsc positively associated m2 macrophage polarization vitro experiments confirmed interleukin6 il6 secreted mscs upon transforming growth factor1 stimulation promotes m2 macrophage polarizationconclusionsin dialysisinduced peritoneal fibrosis mscs situated inflammatory environment tgf1 secrete il6 polarize macrophages m2 phenotype findings reveal previously unidentified role tissue macrophage antifibrotic process adsc advantage abundance accessibility making application values extremely promisinggraphical abstractin dialysisinduced peritoneal fibrosis peritoneal mesothelial cells secrete transforming growth factor1 tgf1 exposed methylglyoxal mgo containing peritoneal dialysate situated tgf1 inflammatory environment induces mesenchymal stem cells secrete interleukin6 il6 il6 polarizes macrophages m2 phenotype dominant peritoneal tissue m2 macrophages marked upregulated arg1 expression account attenuation mgoinduced dedifferentiation peritoneal mesothelial cells maintain epithelial integrity,0.0
effects menopause women multiple sclerosis evidencebased review front neurol 2021 mar 19 12554375 doi 103389 fneur2021554375 ecollection 2021abstractover two thirds individuals develop multiple sclerosis ms will women prior age menopause estimated 30 current ms population consists peri postmenopausal women presence ms appear influence age menopausal onset clinical practice symptoms ms menopause can frequently overlap including disturbances cognition mood sleep bladder function can create challenges ascertaining likely cause symptoms treated holistic comprehensive approach address common physical psychological changes often suggested patients menopause although studies suggested women ms experience reduced relapse rates increased disability progression post menopause data consistent enough firm conclusions drawn mechanisms postmenopausal women ms may experience disability progression include neuroinflammation neurodegeneration ageassociated phenomena immunosenescence inflammaging additional effects likely result reduced levels estrogen affects ms disease course following early retrospective studies women ms receiving steroid hormones recent interventional trials exogenous hormone use albeit oral contraceptive provided indications potential benefit ms outcomes review summarizes current research effects menopause women ms including psychological impact symptoms menopause disease worsening treatment options finally highlight need inclusion ms patients underrepresented racial geographic groups clinical trials including among menopausal womenpmid33815241 pmcpmc8017266 doi103389 fneur2021554375,0.0
diffusion tensor imaging revealed different pathological processes white matter hyperintensities background although increasing evidence showed correlations white matter hyperintensities wmhs cognitive impairment relationship still modest many researchers began focus variation caused heterogeneity wmh tried explore pathological heterogeneity wmh using diffusion tensor imaging dti provide new insight future researchmethodsdiffusion weighted images dwis brain acquired 73 patients wmh 18 healthy controls modeled dti measured fractional anisotropy fa mean diffusivity md axial diffusivity ad radial diffusivity rd white matter periventricular frontal lobe pfl periventricular occipital lobe pol periventricular parietal lobe ppl deep centrum ovales dco grouped measures according fazekas scale compared dti metrics different regions fazekas scale graderesultssignificantly lower fa values p 0001 higher md p 0001 rd values p 0001 associated wmh observed periventricular frontal lobe pfl compared regions fazekas grades ad wmh pfl higher ppl dco differences groups high md rd indicated effect size normal control group dti metrics pfl regions significantly different less significant different difference dti metrics wmh ppl pol dco lower normal white matter indicated effect sizeconclusiondistinct pathological processes can revealed dti frontal periventricular wmh regions processes may represent effects severe demyelination within frontal periventricular wmh,1.0
hip pathologies mucopolysaccharidosis type iii background mucopolysaccharidosis type iii mps iii comprises group rare lysosomal storage diseases although musculoskeletal symptoms less pronounced mps subtypes pathologies hip spine reported mps iii patients purpose study describe hip pathologies influencing parameters mps iii patientsmethodsa retrospective chart review performed 101 mps iii patients thirtytwo patients met inclusion criteria enzymatically genetically confirmed diagnosis anteroposterior radiograph hips modified ficat classification wibergs centeredge angle reimers migration percentage measuredresultsthe mean age data assessment 110 years sd 57 osteonecrosis femoral head observed 17 32 patients statistically significant association found changes age sex mps iii subtype patients severe phenotype showed significantly higher rates osteonecrosis 14 17 patients intermediate phenotype hip dysplasia present 9 32 patients significantly associated osteonecrosis femoral head p 004 conclusionsthe present study demonstrates high rate hip pathologies mps iii patients hip dysplasia severe phenotype significantly correlated osteonecrosis femoral head therefore radiographs hips highly recommended baseline followup assessments mps iii patientstrial registrationretrospectively registered,0.0
impaired binaural hearing adults selected review literature front neurosci 2021 mar 19 15610957 doi 103389 fnins2021610957 ecollection 2021abstractdespite 100 years study still many fundamental questions binaural hearing remain unanswered including impairments binaural function related mechanisms binaural hearing review focuses number studies fundamental understanding known effects peripheral hearing loss aging traumatic brain injury strokes brain tumors multiple sclerosis ms binaural function literature reviewed makes clear conditions potential impair binaural system specific abilities given patient known without performing multiple behavioral neurophysiological measurements binaural sensitivity future work area potential bring awareness binaural dysfunction patients clinicians well deeper understanding mechanisms binaural hearing will require integration clinical research animal computational modeling approachespmid33815037 pmcpmc8017161 doi103389 fnins2021610957,0.0
capillaroscopy diagnostic tool diagnosis mixed connective tissue disease mctd case report background concept mixed connective tissue disease mctd unique connective tissue disease endured half century disease onset can adulthood mctd juvenile onset jmctd characterized overlapping features systemic lupus erythematosus sle polymyositis dermatomyositis pm dm systemic sclerosis ssc universally accepted classification criteria mctd exists however agreed upon overlapping disease features include presence high titers u1 small nuclear ribonucleoprotein particle antibodies u1snrnp peripheral blood raynauds phenomenon synovitis myositis swollen hands fingers characteristic capillaroscopy findings commonly seen mctd jmctd may represent crucial key clue classification well prognosis patientscase presentationwe present young male patient symptom onset early age 13 diagnosed mctd age 16 found high titers antiu1snrnp antibodies raynauds phenomenon synovitis swollen hands fingers interestingly video capillaroscopy diagnosis abnormal revealed active ssclike pattern presentation course describedconclusionswe conclude based existing data highlighted case presentation nailfold video capillaroscopy included early screening tool detection microangiopathy patients diagnosis mctd jmctd additionally given prevalence population disease diagnosis recommend consideration given nailfold video capillaroscopy potentially important classification criteria prognostic tool jmctd mctd,0.0
earlyonset multiple sclerosis frequent relapses challenging diagnosis less favorable prognosis cureus 2021 mar 18 13 3 e13963 doi 107759 cureus13963abstractpediatric multiple sclerosis ms rare demyelinating disease brain spinal cord optic nerve caused immune modulators mediating neuronal axons central nervous system ms usually characterized series neurological events without features encephalopathy separated time space complications arise permanent degeneration nerves condition can diagnosed based international pediatric multiple sclerosis study group diagnostic criteria definitive treatment ms report case male child diagnosed ms age six years presented right hemiparesis visual impairment subsequently multiple relapses varied neurological presentations relapse treated methylprednisolonepmid33880297 pmcpmc8052520 doi107759 cureus13963,1.0
high prevalence fatigue contemporary patients multiple sclerosis mult scler j exp transl clin 2021 mar 18 7 1 2055217321999826 doi 101177 2055217321999826 ecollection 2021 janmarabstractobjective prevalence multiple sclerosis ms related fatigue may changed due new diagnostic criteria new disease modifying drugs aimed assess prevalence fatigue contemporary ms cohort explore associations fatigue clinical demographic factorsmethods crosssectional study ms population three norwegian counties fatigue assessed fatigue scale motor cognitive functions fsmc also assessed selfreported anxiety depression daytime sleepinessresults response rate 64 1599 2512 mean age participants 52 13 years median edss 25 iqr 1530 median disease duration onset 16 years iqr 825 found prevalence fatigue 81 women higher prevalence fatigue men 83 vs 78 p 002 prevalence increased age p 0001 increasing disease severity p 0001 multivariate analyses sex disease severity remained independent determinants fatigue anxiety depression daytime sleepiness prevalent patients fatigue without fatigue pvalues 0001 conclusion prevalence fatigue high contemporary patients ms fatigue associated female sex level disability well anxiety depression excessive daytime sleepinesspmid33796331 pmcpmc7985949 doi101177 2055217321999826,0.0
repair abilities mouse autologous adiposederived stem cells shakegel3d complex local injection intrauterine adhesion bmp7smad5 signaling pathway activation background objective explore therapeutic effect autologous adiposederived stem cells adscs combined shakegel3d transplantation activate bmp7smad5 signaling pathway treat intrauterine adhesions iua methodsautologous adscs isolated merged shakegel3d iua model established mechanical injury third generation autologous adscs injected directly uterus combination shakegel3d 7 days treatment endometrial morphology number endometrial glands endometrial fibrosis area fibrosis biomarker analysis rtpcr ihc examined bmp7 phosphorylation smad5 also detected recovery infertility function treated mice evaluatedresultsfluorescenceactivated cell sorting facs showed autologous adscs expressed cd105 991 cd29 996 cd73 989 autologous adscs still maintain good growth state shakegel3d histological examination revealed number endometrial glands increased significantly area fibrosis decreased time expression bmp7 smad5 adscs + gel group significantly upregulated final reproductive function group partly recoveredconclusionsautologous adscs can used combination shakegel3d maintain functionality create viable threedimensional growth environment combined transplantation autologous adscs shakegel3d promotes recovery damaged endometrial tissue increasing bmp7smad5 signal transduction resulting endometrium thickening increased number glands decreased fibrosis leading restoration partial fertility,0.0
deletion arginase 2 attenuates neuroinflammation experimental model optic neuritis plos one 2021 mar 18 16 3 e0247901 doi 101371 journalpone0247901 ecollection 2021abstractvision impairment due optic neuritis one major clinical presentations multiple sclerosis ms characterized inflammation degeneration optic nerve retina currently available treatments partially effective limited impact neuroinflammatory pathology disease recent study laboratory highlighted beneficial effect arginase 2 a2 deletion suppressing retinal neurodegeneration inflammation experimental model ms utilizing model present study investigated impact a2 deficiency msinduced optic neuritis experimental autoimmune encephalomyelitis eae induced wildtype wt a2 knockout a2 mice eaeinduced cellular infiltration well activation microglia macrophages reduced a2 optic nerves axonal degeneration demyelination seen eae optic nerves observed reduced a2 deletion lack a2 significantly ameliorated astrogliosis induced eae conclusion findings demonstrate critical involvement arginase 2 mediating neuroinflammation optic neuritis suggest potential a2 blockade targeted therapy msinduced optic neuritispmid33735314 doi101371 journalpone0247901,1.0
alterations mesenchymal stromal cells cerebrospinal fluid insights transcriptomics als clinical trial background mesenchymal stromal cells mscs studied increasing intensity clinicians researchers strive understand ability mscs modulate disease progression promote tissue regeneration mscs used diverse applications important appreciate specific physiological environments may stimulate changes alter phenotype cells one need neuroregenerative applications characterize spectrum msc responses cerebrospinal fluid csf environment injection intrathecal space mechanistic understanding cellular biology response csf environment may predict ability mscs promote injury repair provide neuroprotection neurodegenerative diseasesmethodsin study characterized changes morphology metabolism gene expression occurring human adiposederived mscs cultured human hcsf artificial csf acsf well examined relevant protein levels csf subjects treated mscs amyotrophic lateral sclerosis als resultsour results demonstrated intrathecallike conditions mscs retained morphology though became quiescent largescale transcriptomic analysis mscs revealed distinct gene expression profile cells cultured acsf acsf culture environment induced expression genes related angiogenesis immunomodulation addition mscs acsf expressed genes encoding nutritional growth factors expression levels control cells furthermore observed dosedependent increase growth factors immunomodulatory cytokines csf subjects als treated intrathecally autologous mscsconclusionsoverall results suggest mscs injected intrathecal space ongoing clinical trials remain viable may provide therapeutic benefit patients,0.0
mesenchymal stem stromal cells valuable source treatment immunemediated disorders abstractover recent years mesenchymal stem stromal cells mscs potential biomedical applications received much attention global scientific community increasing manner firstly mscs successfully isolated human bone marrow bm next steps also extracted sources mostly umbilical cord uc adipose tissue international society cellular therapy isct suggested minimum criteria identify characterize mscs follows plastic adherence surface expression cd73 d90 cd105 lack expression cd14 cd34 cd45 human leucocyte antigendr hladr also capability differentiate multiple cell types including adipocyte chondrocyte osteoblast vitro depends culture conditions however distinct properties including selfrenewability multipotency easy accessibility just one side coin another side huge secretome comprised hundreds mediators cytokines signaling molecules can effectively modulate inflammatory responses control infiltration process finally leads regulated tissue repair healing regeneration process mscmediated immunomodulation direct result harmonic synergy mscreleased signaling molecules ie mediators cytokines chemokines reaction immune cells target cells molecules also feedback mscmoleculetarget cell axis features make mscs respectable eligible therapeutic candidate evaluated immunemediated disorders graft versus host diseases gvhd multiple sclerosis ms crohns disease cd osteoarthritis oa even immunedysregulating infectious diseases novel coronavirus disease 2019 covid19 paper discussed therapeutic applications msc secretome biomedical aspects related immunemediated conditions sources msc extraction migration homing properties therapeutic molecules released mscs pathways molecular mechanisms possibly involved exceptional immunoregulatory competence mscs discussed besides novel discoveries recent findings immunomodulatory plasticity mscs clinical applications methods required use effective therapeutic option patients immunemediated immunedysregulating diseases highlighted,0.0
epley manoeuvre posterior semicircular canal benign paroxysmal positional vertigo people multiple sclerosis protocol randomised controlled trial bmj open 2021 mar 18 11 3 e046510 doi 101136 bmjopen2020046510abstractintroduction vestibular disorders multiple sclerosis ms central peripheral origin although central aetiology expected ms peripheral damage also significant disease prevalent effect vestibular peripheral damage benign paroxysmal positional vertigo bppv impairments posterior semicircular canals represent 6090 cases bppv standard gold treatment syndrome epley manoeuvre em effectiveness poorly studied patients ms one retrospective research study case study reported encouraging results em regard resolution posterior semicircular canal bppv aim future randomised controlled trial rct assess effectiveness em bppv participants ms compared sham manoeuvremethods analysis current protocol describes rct twoarm parallelgroup design randomisation concealed allocation doubleblinding will conducted reduce possible bias participants evaluators will blinded group allocation least 80 participants meet eligibility criteria will recruited participants will em sham manoeuvre performed within experimental control group respectively primary outcome study changes dix hallpike test secondary outcome will changes selfperceived scales dizziness handicap inventory vestibular disorders activities daily living scale sample will evaluated baseline immediately intervention 48 hours postinterventionethics dissemination study approved andalusian review board ethics committee virgen macarenavirgen del rocio hospitals id 0107n20 23 july 2020 results research will disseminated investigators peerreviewed journalstrial registration number nct04578262pmid33737443 doi101136 bmjopen2020046510,0.0
effect hand foot acupuncture twelve needles hemiplegia patients qi deficiency blood stasis syndrome convalescent stage ischaemic stroke study protocol randomised controlled trial background hemiplegia common sequela stroke acupuncture one common physical therapies used treat hemiplegia recovery stage ischaemic stroke hand foot acupuncture twelve needles acupuncture treatment performed stroke principal objective study assess efficacy safety hand foot acupuncture twelve needles hemiplegia convalescent stage ischaemic strokemethodsthis protocol randomised controlled clinical trial two groups hand foot acupuncture twelve needles group routine acupuncture group total 208 participants will randomly assigned two different groups 11 ratio will undergo conventional rehabilitation limb function will evaluated simplified fuglmeyer assessment scale barthel index modified ashworth scale national institute health stroke scale participants will evaluated baseline day enrolment followed 2 weeks 1 month 2 months 3 months enrolmentdiscussionthe results study will provide evidence effectiveness hand foot acupuncture twelve needles treatment limb dysfunction can used future evaluationstrial registrationchictrorgcnchictr1900021774 registered 8 march 2019,0.0
bayesian approach predicting responses therapy highdimensional timecourse gene expression profiles background historical updated information provided timecourse data collected entire treatment period proves useful information provided singlepoint data accurate predictions made using timecourse data multiple biomarkers indicate patients response therapy contribute positively decisionmaking process associated designing effective treatment programs various diseases therefore development prediction methods incorporating timecourse data multiple markers necessaryresultswe proposed new methods may used prediction gene selection via timecourse gene expression profiles prediction method consolidated multiple probabilities calculated using gene expression profiles collected series time points predict therapy response using two data sets collected patients hepatitis c virus hcv infection multiple sclerosis ms performed numerical experiments predicted response therapy evaluated accuracies methods accurate conventional methods successfully selected genes functions associated pathology hcv infection msconclusionsthe proposed method accurately predicted response therapy using data multiple time points showed higher accuracies early time points compared conventional methods furthermore method successfully selected genes directly associated diseases,0.0
new insights socioeconomic aspects multiple sclerosis cohort polish patients ann agric environ med 2021 mar 18 28 1 99106 doi 1026444 aaem 117962 epub 2020 feb 24abstractintroduction objective diagnosis multiple sclerosis ms affects socioeconomic aspects patients lives poses new challenges objectives study 1 determine selected socioeconomic aspects ms poland relation disease type patients place residence 2 evaluate profile patients via ms society mss occupational consequences informing employer diagnosismaterial methods retrospective observational study undertaken assess cohort 375 polish ms patients socioeconomic data collected based patients responses questions questionnaire clinical data obtained available medical recordsresults patients relapsingremitting ms significantly longer time occupational activity higher economic status higher level education better relationships life partner less likely benefit disability benefits members mss patients progressive types disease patients living rural areas significantly shorter time occupational activity often experienced decrease income received disability pension less educated urban residents patients informed employer ms diagnosis significantly often received support company professionally active longer less likely experience decrease income membership mss dominated patients progressive variants disease advanced disabilityconclusions disease variant lesser extent place residence affected socioeconomic aspects ms might advantageous patient disclose information ms diagnosis employerpmid33775074 doi1026444 aaem 117962,0.0
generation ucipscderived neurospheres cell therapy application background neural stem cell nsc therapy remains one potential approaches treatment neurological disorders discovery human induced pluripotent stem cells hipscs establishment hipscderived human neural stem cells hinscs revolutionized technique cell therapy meanwhile often required nscs stored transported long distance research treatment purposes although high survival rates maintained conventional methods cell transportation dry ice liquid nitrogen inconvenient expensive therefore establishment safe affordable lowcost strategy store transport easily accessible hipscs hinscs characteristics match fetal hnscs incredibly urgentmethodswe reprogrammed human urinary cells ipscs using nonintegrating virusfree technique differentiated ipscs toward inscs neurospheres neurons good manufacturing practice gmp compatible conditions pluripotency ipscs inscs characterized series classical methods surface markers karyotype analysis vitro well vivo differentiation capabilities etc resultshere results showed successfully generated hinscs neurospheres available noninvasive acceptable urinary cells virusfree technique next demonstrated inscs differentiated mature cerebral cortical neurons neural networks interestingly hinscs survived longer neurospheres ambient temperature cultured monolayer within 7 days approximately neural viability remained 80 hinscs cultured monolayer died almost immediately neurospheres exposed placed standard culture conditions 37 c 5 co2 recovered typical morphology retained proliferation differentiation abilitiesconclusionsin study provided simple method storage nscs neurospheres alternative method costly inconvenient traditional methods cryopreservation will enable hinscs transported long distances facilitate therapeutic application nscs neurospheres without treatment,0.0
comparing diagnostic value echocardiography stroke ceis results prospective observatory cohort study background echocardiography one main diagnostic tools diagnostic workup stroke already well integrated clinical workup however value transthoracic vs transesophageal echocardiography tte tee stroke patients still matter debate aim study characterize relevant findings tte tee management stroke patients correlate subsequent clinical decisions therapiesmethodswe evaluated n 107 patients admitted ischemic stroke transient ischemic attack stroke unit university medical center underwent tte tee examination different blinded investigatorsresultsmajor cardiac risk factors found 8 98 82 patients minor cardiac risk factors stroke found 108 cases found change therapeutic regime tte tee 22 225 cases 5 5 cases tee leads change therapeutic regime 4 4 tte 13 cases 133 tte tee lead change therapeutic regime major therapy change indication close patent foramen ovale pfo 9 92 patients tte 10 102 patients tee p 1000 conclusionmajor finding clinical impact therapy change detection pfo detection pfo tte non inferior tee implicating tte serves good screening tool detection pfo especially young age patientstrial registrationthe trial registered approved prior inclusion local ethics committee 1 3 17,0.0
treatment switching discontinuation 20 years big multiple sclerosis data network front neurol 2021 mar 17 12647811 doi 103389 fneur2021647811 ecollection 2021abstractbackground although dozen disease modifying treatments dmts available relapsing forms multiple sclerosis ms treatment interruption switching discontinuation common challenges objective study describe treatment interruption discontinuation big ms data network methods merged information 269 822 treatment episodes 110 326 patients 1997 2016 five clinical registries cohort study treatment stop defined clinician recorded dmt end reason included treatment interruptions switching alternate dmts longterm permanent discontinuations results incidence dmt stopping cross full observation period lowest fty 197 per 100 personyears py treatment 95 ci 192201 followed nat 226 100 py 95 ci 222230 ifn 233 100 py 95 ci 232235 184 013 observed dmt stops 159 309 866 switched alternate dmt within 6 months reasons stopping drug stable observation period lack efficacy common reason followed lack tolerance side effects proportion patients continuing dmts similarly stable 2014 2015 drop 83 75 noted conclusions dmt stopping reasons rates mostly stable time slight increase recent years availability dmts overall results suggest discontinuation ms dmts mostly due dmt properties lesser extent risk management competitive marketpmid33815259 pmcpmc8010264 doi103389 fneur2021647811,0.0
elevated levels inflammatory plasma biomarkers associated risk hiv infection background determine individuals hiv1 serodiscordant couple cohorts rwanda zambia become hivpositive distinct inflammatory biomarker profile compared individuals remain hivnegative compared levels biomarkers plasma hivnegative individuals either seroconverted preinfection became hivpositive remained hivnegative uninfected resultswe observed individuals combined cohort well individual country cohorts later became hiv1 infected significantly higher baseline levels multiple inflammatory cytokines chemokines compared individuals remained hivnegative genital inflammation ulceration schistosome infections associated elevated profile defined levels itac il7 significant predictors later hiv acquisition roc predictive analyses whereas classical th1 th2 inflammatory cytokines il12 interferon il4 il5 il13 notconclusionsoverall data show significant association increased plasma biomarkers linked inflammation immune activation hiv acquisition suggests preexisting conditions increase systemic biomarkers represent factor increased risk hiv infection,0.0
management severe graves#39 hyperthyroidism pregnancy following immune reconstitution therapy multiple sclerosis j endocr soc 2021 mar 17 5 6 bvab044 doi 101210 jendso bvab044 ecollection 2021 jun 1abstractcontext alemtuzumab alz cd52 monoclonal antibody highly efficacious multiple sclerosis however side effects common autoimmune thyroid disease graves disease hashimoto thyroiditis wellknown complication alz treatment alzinduced graves disease can challenging even difficult pregnancycase description present case severe alzinduced graves disease rapid increase thyrotropin receptor antibodies trab 240 iu l thyrotoxicosis early pregnancy treatment high doses antithyroid medication needed high risk fetal neonatal thyrotoxicosis serial fetal sonography showed normal development newborn baby presented high levels trab 240 iu l developed neonatal thyrotoxicosis day 8 adequate monitoring treatment followup newborn baby ensured normal thyroid function disappearance trab 6 weeks birthconclusion multiple sclerosis patients treated alz may develop severe graves disease increased risk fetal neonatal thyrotoxicosis close followup multidisciplinary approach needed ensure healthy outcomepmid34017934 pmcpmc8122367 doi101210 jendso bvab044,0.0
uncovering sex differences rodent microglia abstractthere inherent structural functional differences central nervous systems cns females males gradually established sexspecific differences due spectrum genetic epigenetic hormonal factors actively contribute differential incidences disease courses even outcomes cns diseases sexes microglia principle resident macrophages cns play crucial role cns physiology pathology however sex differences microglia relatively unexplored recently emerging data convincingly demonstrated existence sexdependent structural functional differences rodent microglia consequently changing current understanding versatile cells review attempt comprehensively outline current advances revealing microglial sex differences rodent potential implications specific cns diseases stark sex difference detailed understanding molecular processes underlying microglial sex differences major importance design translational sex microgliaspecific therapeutic approaches,0.0
exomewide search genes associated central nervous system inflammatory demyelinating diseases following chikv infection tip iceberg front genet 2021 mar 17 12639364 doi 103389 fgene2021639364 ecollection 2021abstractchikungunya virus chikv reemergent arbovirus causes disease characterized primarily fever rash severe persistent polyarthralgia although 1 cases develop severe neurological manifestations inflammatory demyelinating diseases idd central nervous system cns like acute disseminated encephalomyelitis adem extensive transverse myelitis genetic factors associated host response disease severity still poorly understood study performed wholeexome sequencing wes identify hla alleles genes cellular pathways associated cns idd clinical phenotype outcomes following chikv infection cohort includes 345 patients 160 confirmed chikv six cases presented neurological manifestation mimetizing cns idd wes data analysis performed 12 patients including cns idd cases 6 chikv patients without neurological manifestation identified 29 candidate genes harboring rare pathogenic probably pathogenic variants exomes analyzed hla alleles also determined patients developed cns idd shared common signature diseases multiple sclerosis ms neuromyelitis optica spectrum disorders nmosd genes included gene ontology analyses pathways associated cns idd syndromes retrieved suggesting chikvinduced cns outcomesmay share genetic background neurological disorders knowledge study first genomewide investigation genetic risk factors cns phenotypes chikv infection data suggest hladrb1 alleles associated demyelinating diseases may also confer risk cns idd outcomes patients chikv infectionpmid33815474 pmcpmc8010313 doi103389 fgene2021639364,1.0
immunerelated genes larval holotrichia parallela response entomopathogenic nematodes heterorhabditis beicherriana lf background entomopathogenic nematodes epns emerge compatible alternatives conventional insecticides controlling holotrichia parallela larvae coleoptera scarabaeidae however immune responses h parallela epns infection remain unclearresultsin present research rnaseq firstly performed total 89 427 85 741 unigenes achieved midgut h parallela larvae treated heterorhabditis beicherriana lf 24 72 h respectively 2545 3156 unigenes differentially regulated respectively among differentially expressed genes degs 74 identified potentially related immune response notably immunerelated genes peptidoglycan recognition protein sc1 pgrpsc1 prophenoloxidase activating enzymei ppaei glutathione stransferase gst induced treatment points bioinformatics analysis showed pgrpsc1 ppaei gst involved antiparasitic immune process quantitative realtime pcr qrtpcr results showed three immunerelated genes expressed developmental stages pgrpsc1 ppaei higher expressions midgut fat body respectively gst exhibited high expression moreover vivo silencing resulted increased susceptibility h parallela larvae h beicherriana lfconclusionthese results suggest h parallela pgrpsc1 ppaei gst involved immune responses resist h beicherriana lf infection study provides first comprehensive transcriptome resource h parallela exposure nematode challenge will help support comparative studies hostepn interactions,0.0
reduction leukemic burden via bonetargeted nanoparticle delivery inhibitor cchemokine cc motif ligand 3 ccl3 signaling abstractleukemias challenging diseases treat due part interactions leukemia cells bone marrow microenvironment bmme contribute significantly disease progression studies shown leukemic cells secrete cchemokine cc motif ligand 3 ccl3 disrupt bmme resulting loss hematopoiesis support leukemic cell survival proliferation study murine model blast crisis chronic myelogenous leukemia bccml expresses translocation products bcr abl nup98 hoxa9 used determine role ccl3 bmme regulation leukemic cells derived ccl3 mice shown minimally engraft normal bmme thereby demonstrating ccl3 signaling necessary recapitulate bccml disease analysis showed disruption hematopoiesis within bmme bccml model rescue altered bmme therapeutic inhibition ccl3 signaling investigated using bonetargeted nanoparticles np deliver maraviroc inhibitor cc chemokine receptor type 5 ccr5 ccl3 receptor npmediated maraviroc delivery partially restored bmme significantly reduced leukemic burden improved survival overall results demonstrate inhibiting ccl3 via ccr5 antagonism potential therapeutic approach restore normal hematopoiesis well reduce leukemic burden within bmme,0.0
case interstitial pneumonia associated systemic sclerosis primary peritoneal serous carcinoma successfully treated cyclophosphamide int cancer conf j 2021 mar 16 10 3 197200 doi 101007 s13691021004751 ecollection 2021 julabstracta 62yearold woman edema color changes fingers underwent computed tomography ct slight interstitial changes detected lungs multiple tumors anterior hilar region liver based blood test findings diagnosed interstitial pneumonia associated systemic sclerosis ultrasoundguided biopsy hepatic hilar lymph node revealed poorly differentiated serous adenocarcinoma cells high serum ca125 levels suggested primary peritoneal serous carcinoma ppsc owing increased interstitial shadows chest ct images worsening respiratory distress intravenous cyclophosphamide oral prednisolone treatment started skinrelated symptoms respiratory distress interstitial shadows improved tumor size reduced eighteen months later patient exacerbation interstitial pneumonia ppsc well controlledpmid34221831 pmcpmc8206247 doi101007 s13691021004751,0.0
bet bromodomain inhibitors pfi1 jq1 identified epigenetic compound screen enhance c9orf72 gene expression shown ameliorate c9orf72associated pathological behavioral abnormalities c9als ftd model background intronic ggggcc g4c2 hexanucleotide repeat expansion hre c9orf72 gene common cause amyotrophic lateral sclerosis als frontotemporal dementia ftd referred c9als ftd cure effective treatment exist c9als ftd three major molecular mechanisms emerged explain c9als ftd disease mechanisms 1 c9orf72 lossoffunction haploinsufficiency 2 dipeptide repeat dpr proteins mediated toxicity translation repeat rnas controversial 3 rnamediated toxicity bidirectional transcription repeats form intranuclear rna foci recent studies indicate doublehit pathogenic mechanism c9als ftd reduced c9orf72 protein levels lead impaired clearance toxic dprs explored whether pharmacological compounds can revert pathological hallmarks vitro cognitive impairment c9als ftd mouse model c9bac specifically focused study small molecule inhibitors targeting chromatinregulating proteins epidrugs goal increasing c9orf72 gene expression reduce toxic dprsresultswe generated luciferase reporter cell lines containing 10 control 90 mutant g4c2 hre located exon 1a 1b human c9orf72 gene screen 14 different epidrugs targeting bromodomains chromodomains histonemodifying enzymes found several bromodomain extraterminal domain bet inhibitors beti including pfi1 jq1 increased luciferase reporter activity using primary cortical cultures c9bac mice found pfi1 treatment increased expression v1v3 transcripts human mutant c9orf72 gene reduced poly gp dpr inclusions enhanced intranuclear rna foci also tested whether jq1 beti previously shown reach mouse brain intraperitoneal ip injection can revert behavioral abnormalities c9bac mice interestingly found jq1 administration daily ip administration 7 days rescued hippocampaldependent cognitive deficits c9bac miceconclusionsour findings place bet bromodomain inhibitors potential therapy c9als ftd ameliorating c9orf72associated pathological behavioral abnormalities finding pfi1 increases accumulation intranuclear rna foci agreement recent data flies suggesting nuclear rna foci can neuroprotective sequestering repeat transcripts result toxic dprs,1.0
brainderived neurotrophic factor val66met polymorphism can protect cognitive impairment multiple sclerosis front neurol 2021 mar 16 12645220 doi 103389 fneur2021645220 ecollection 2021abstractintroduction brainderived neurotrophic factor bdnf member neurotrophin family involved neuronal survival synaptic plasticity bdnf val66met polymorphism known reduce bdnf expression secretion role multiple sclerosis ms poorly investigated objectives methods multicenter retrospective study assessed role bdnf val66met polymorphism cognitive motor disability ms patients consecutively referred university florence hospital barletta patients underwent genetic analysis presence val66met polymorphism comprehensive neuropsychological examination raos brief repeatable battery stroop color word test possible predictors expanded disability status scale edss score number failed neuropsychological tests assessed linear multivariable regression models results ninetyeight patients recruited patients bdnf val66met polymorphism 357 frequently males p 0020 disabled p 0026 marginally older p 0064 multivariable analysis bdnf val66met polymorphism associated better cognitive performance b 11 05 p 0027 higher edss score associated progressive disease course b 34 p 0001 marginally presence bdnf val66met polymorphism b 056 p 0066 discussion results preliminarily suggest protective role bdnf val66met polymorphism cognitive impairment ms patients possibly related detrimental effect increased bdnf concentration neuroinflammatory environmentpmid33815257 pmcpmc8011315 doi103389 fneur2021645220,0.0
sulfasalazine modifies metabolic profiles enhances cisplatin chemosensitivity cholangiocarcinoma cells vitro vivo models background sulfasalazine ssz widely known xct inhibitor suppressing cd44v9expressed cancer stemlike cells cscs related redox regulation cholangiocarcinoma cca high recurrence rate effective chemotherapy recent report revealed high levels cd44v9positive cells cca patients therefore combination drugs prove suitable strategy cca treatment via individual metabolic profilingmethodswe examined effect xcttargeted cd44v9cscs using sulfasalazine combined cisplatin cis gemcitabine cca vitro vivo models nmrbased metabolomics analysis xenograft mice tumor tissuesresultsour findings suggest combined ssz cis leads higher inhibition cell proliferation induction cell death cis alone vitro vivo models xenograft mice showed cd44v9csc marker ck19cca proliferative marker reduced combination treatment interestingly different metabolic signatures significant metabolites observed drugtreated group compared control group revealed cancer suppression mechanismsconclusionsssz improve cca therapy sensitization cis killing cd44v9positive cells modifying metabolic pathways particular tryptophan degradation ie kynurenine pathway serotonin pathway nucleic acid metabolism,0.0
bu shen yi sui capsule alleviates neuroinflammation demyelination promoting microglia toward m2 polarization correlates changes mir124 mir155 experimental autoimmune encephalomyelitis oxid med cell longev 2021 mar 16 20215521503 doi 101155 2021 5521503 ecollection 2021abstractbackground bu shen yi sui capsule bsys traditional chinese medicine prescription shown antineuroinflammatory neuroprotective effects treating multiple sclerosis ms animal model experimental autoimmune encephalomyelitis eae microglia play important role neuroinflammation m1 phenotype microglia involved proinflammatory process disease m2 phenotype plays antiinflammatory role promoting polarization microglia m2 ms eae promising therapeutic strategy study aimed exploring effects bsys microglial polarization mice eaemethods eae model established intraperitoneal injection pertussis toxin subcutaneous injection myelin oligodendrocyte glycoprotein mog 3555 c57bl 6j mice mice treated bsys 302 g kg fty720 03 mg kg distilled water intragastric administration lfb staining transmission electron microscopy qrtpcr immunofluorescence elisa fluorescence situ hybridization western blotting used detect histological changes myelin microglial m1 m2 polarization markers expression key genes involved eae results conclusions bsys treatment eae mice increased body weight decreased clinical score reduced demyelination induced inflammatory infiltration bsys also inhibited mrna expression m1 microglial markers increasing mrna level m2 markers additionally bsys led marked decrease ratio m1 microglia inos+ iba1+ obvious increase number m2 microglia arg1+ iba1+ eae mouse model mir124 expression decreased mir155 expression increased bsys treatment significantly reversed effect modulated levels c ebp pu1 socs1 target genes mir124 mir155 therefore neuroprotective effect bsys ms eae related promoting microglia toward m2 polarization may correlated changes mir124 mir155 vivopmid33815654 pmcpmc7987454 doi101155 2021 5521503,1.0
webbased physical activity intervention people progressive multiple sclerosis application consensusbased intervention development guidance bmj open 2021 mar 16 11 3 e045378 doi 101136 bmjopen2020045378abstractobjectives people progressive multiple sclerosis pwpms report recognise benefits activity physical psychological health need support achieve physical activity goals aimed systematically develop theoretically informed intervention enable pwpms readily engage regular physical activitydesign used intervention mapping approach inform intervention developmentsetting conducted semistructured interviews pwpms families carers physiotherapists recruited secondary care settingsparticipants fourteen pwpms expanded disability status scale score 6 8 7 families carers 13 physiotherapists 1 physiotherapy technician participatedresults interview data suggested development supportive coaching relationships physiotherapists promote ability pwpms achieve desirable achievable physical activity plan interview data informed prototype lifestyle exercise activity package multiple sclerosis leapms consisting secure multiuser webbased platform education activity suite interactive components enabling selection exercises goal setting activity logging six flexible facetoface webbased physiotherapy coaching sessions remote support via embedded webbased messaging function together draw specific theorybased methods achieve physical activity behaviour change namely active learning reinforcement modelling feedback facilitation goal setting guided practice implementation within multiuser platform accessible participants trained physiotherapists researchersconclusions followed inclusive systematic transparent process develop leapms intervention enables detailed description components context guiding principles inform ongoing evaluation importantly pwpms expressed need autonomy developing physical activity plans achieved embedding selfmanagement principles design delivery leapms interventionpmid33727274 doi101136 bmjopen2020045378,0.0
trait mindfulness primarily associated depression fatigue multiple sclerosis ms implications mindfulnessbased interventions abstractobjectivespersons ms pwms often display symptoms depression fatigue mindfulnessbased interventions known counteract symptoms however todate exact relations trait mindfulness depression fatigue remain examined fatigue generally regarded symptom immanent disease direct neurobiological consequence increased cytokine levels cortical atrophy depression hand psychosocial factors context adaptation difficulties probably higher relevance hence one may argue mindfulness trait promotes successful adaption may show strong negative association depression relatively minor negative association fatigue pwmsmethodsin current study association selfreported trait mindfulness fatigue depression examined sample 69 pwmsresultstrait mindfulness showed highly significant negative correlations depression fatigue mediation analyses however revealed depression mediated relation mindfulness fatigueconclusionit may concluded pwms trait mindfulness shows genuine negative association depression secondarily associated fatigue implications mindfulnessbased interventions ms discussed based results current study may feasible promote acceptance default fatigue symptoms instead actual reduction fatigue symptoms,0.0
effects positive thinking program hope sleep quality iranian patients thalassemia randomized clinical trial background thalassemia negative impact patients psychological health sleep quality study aimed determine effects positive thinking training program hope sleep quality patients thalassemia majormethodsthis randomized clinical trial conducted 78 patients thalassemia major including 36 males 462 42 females 538 mean age 2556 296 iran subjects randomly assigned experimental control groups experimental group received 16 h training based positive thinking materials published martin seligman control group received usual programs data collected baseline well immediately one month intervention using snyders hope scale pittsburgh sleep quality index data analysis performed using spss software 180 statistical tests included independent ttest chisquare mann whitney friedman test significance level set 005 studyresultsthe experimental group significantly higher mean hope score compared control group immediately 4538 782 vs 3532 554 p 0001 one month following intervention 4467 347 vs 35 54 p 0001 moreover mean sleep quality scores experimental group significantly greater control group immediately 535 202 vs 7 24 p 0004 one month intervention 423 22 vs702 303 p 0001 conclusionsince training program positive thinking improved hope quality sleep patients thalassemia major recommend use courses important step toward promotion hope sleep quality among patientstrial registration name registry iranian registry clinical trials trial registration number irct2017010431774n1 url trial registry record https enirctir trial 24923 registration date 07 03 2017,0.0
neurological manifestations predictors severity mortality hospitalized individuals covid19 multicenter prospective clinical study background sthe reports neurological symptoms increasing cases coronavirus disease 2019 covid19 multicenter prospective study conducted determine incidence neurological manifestations hospitalized cases covid19 assess symptoms predictors severity deathmethodshospitalized males females covid19 aged 18 years included study examined two neurologists time admission survived cases followed 8 weeks discharge 16 weeks symptoms improvementsresultswe included 873 participants eligible cases 122 individuals 1397 died hospitalization common nonneurological manifestations fever 811 cough 761 fatigue 361 shortness breath 276 aging male gender comorbidity smoking hemoptysis chest tightness shortness breath associated increased odds severe cases mortality 561 643 cases smell taste dysfunctions hyposmia 586 anosmia 414 dysguesia 100 common among females 697 nonsmokers 667 hyposmia anosmia dysgeusia found associated reduced odds severe cases mortality myalgia 248 headaches 126 dizziness 119 common neurological symptoms headaches negative correlation severity death due covid19 myalgia dizziness associated cerebrovascular events n 10 status epilepticus n 1 neurological findings partial full recovery smell taste dysfunctions found 952 8 weeks 973 16 weeks parosmia 309 phantosmia 90 also reported 8 weeks followup five cases mild headaches 5 cases myalgia reported 16 weeks discharge demyelinating myelitis n 1 guillainbarr syndrome n 1 also found followupconclusionneurological symptoms found prevalent among individuals covid19 disease underestimated current pandemic outbreak,1.0
long noncoding rna norad promotes prostate cancer cell extracellular vesicle release via microrna5413pregulated pkm2 induce bone metastasis prostate cancer background bone metastasis leading cause mortality reduced quality life patients metastatic prostate cancer pca long noncoding rna activated dna damage norad observed abnormal expression various cancers article aimed explore molecular mechanism underlying regulatory role norad bone metastasis pcamethodsnorad expression clinical pca tissues cell lines detected application qrtpcr cancer cells transfected plasmids expressing norad transwell assay cck8 assay carried detect proliferation migration bone metastasis pca norad downstream target molecules screened bioinformatics analysis followed verification using dual luciferase assay extracellular vesicles evs labeled pkh67 interacted bone marrow stromal cells gain lossfunction method applied determine internalization secretion pca cellsderived evs intervention downstream target molecules noradresultspca tissues cell lines observed high expression norad particularly tissues bone metastasis norad knockdown resulted reduced secretion internalization evs suppressed proliferation migration bone metastasis pca cells indicated norad interacted mir5413p leading upregulation pkm2 forced expression pkm2 promoted transfer pkh67labeled evs bone marrow stromal cellsconclusionsnorad might serve cerna mir5413p promote pkm2 expression thereby enhancing development bone metastasis pca promoting internalization transfer evs cancer cells providing insight novel treatment disorder,0.0
axonal loss major sensorimotor tracts associated impaired motor performance minimally disabled multiple sclerosis patients brain commun 2021 mar 16 3 2 fcab032 doi 101093 braincomms fcab032 ecollection 2021abstractmultiple sclerosis neuroinflammatory disease cns associated significant irreversible neuroaxonal loss leading permanent disability thus urgent need vivo markers axonal loss use patient monitoring endpoints trials neuroprotective agents advanced diffusion mri can provide markers diffuse loss axonal fibre density atrophy within specific white matter pathways markers can interrogated specific white matter tracts underpin important functional domains sensorimotor function study aimed evaluate advanced diffusion mri markers axonal loss within major sensorimotor tracts brain correlate degree axonal loss tracts precise kinematic measures hand foot motor control gait minimally disabled people multiple sclerosis twentyeight patients expanded disability status scale 4 kurtzke functional system scores pyramidal cerebellar function 2 18 healthy subjects underwent ultrahigh field 7 tesla diffusion mri calculation fibrespecific measures axonal loss fibre density reflecting diffuse axonal loss fibre crosssection reflecting tract atrophy within three tracts corticospinal tract interhemispheric sensorimotor tract cerebellothalamic tracts visually guided forcematching task involving either hand foot used assess visuomotor control threedimensional markerbased video tracking used assess gait fibrespecific axonal markers tract compared groups correlated visuomotor task performance force error lag gait parameters stance stride length step width single double support patients patients displayed significant regional loss fibre crosssection minimal loss fibre density tracts interest compared healthy subjects familywise error corrected pvalue 005 despite relatively focal lesions within tracts patients reduced axonal fibre density crosssection within corticospinal tracts interhemispheric sensorimotor tracts associated larger force tracking error gait impairments shorter stance smaller step width longer double support familywise error corrected pvalue 005 conclusion significant gait motor control impairments can detected minimally disabled people multiple sclerosis correlated axonal loss major sensorimotor pathways brain given axonal loss irreversible combined use advanced imaging kinematic markers used identify patients risk severe motor impairments emerge aggressive therapeutic interventionspmid34222866 pmcpmc8244644 doi101093 braincomms fcab032,1.0
physical exercise moderates effects disability depression people multiple sclerosis covid19 outbreak j clin med 2021 mar 16 10 6 1234 doi 103390 jcm10061234abstractphysical disability impacts psychosocial wellbeing people multiple sclerosis however role physical activity context still debated taking advantage previous survey conducted online 22 april 7 may 2020 performed posthoc analysis aim assess associations disability physical exercise mental health multiple sclerosis retrieved following data sociodemographic information ii changes lifestyle including exercise iii physical disability measured patientdetermined disease steps scale iv anxiety feelings depressive symptoms assessed via items included quality life neurological disorders measurement system examination interaction plot showed effect disability depression anxious symptoms significant levels physical exercise low b 122 95 ci 085 158 p 0001 moderate b 095 95 ci 066 124 p 0001 high b 068 95 ci 024 113 p 0003 based data can conclude disability significantly impacted depression covid19 pandemic physical activity playing moderating role results suggest favoring exercise multiple sclerosis ms ameliorate psychological wellbeing regardless level physical disabilitypmid33809698 doi103390 jcm10061234,0.0
sex differences bloodbrain barrier neurodegenerative diseases apl bioeng 2021 mar 16 5 1 011509 doi 101063 50035610 ecollection 2021 marabstractthe number people diagnosed neurodegenerative diseases rise many diseases including alzheimers disease parkinsons disease multiple sclerosis motor neuron disease demonstrate clear sexual dimorphisms sex biological variable must now included animal studies sex rarely included vitro models human neurodegenerative disease review describe sexrelated differences neurodegenerative diseases bloodbrain barrier bbb whose dysfunction linked neurodegenerative disease development progression explain potential mechanisms sex sex hormones affect bbb integrity finally summarize current vitro bbb bioengineered models highlight potential study sex differences bbb integrity neurodegenerative diseasepmid33758788 pmcpmc7968933 doi101063 50035610,0.0
case dysembryoplastic neuroepithelial tumor adolescent male cureus 2021 mar 16 13 3 e13917 doi 107759 cureus13917abstractdysembryoplastic neuroepithelial tumors dnets benign mixed glioneuronal neoplasms frequently occur children young adults present case 17yearold male arrived hospital following seizurelike activity magnetic resonance imaging mri scan showed 10 x 8 x 10 mm ovalshaped nonenhancing welldefined mass within right hippocampus patient underwent transcortical approach via middle temporal gyrus resection mass histopathological examination demonstrated presence round uniform cells extensively myxoid background diffuse reactivity glial fibrillary acidic protein gfap dnets considered benign nonrecurring lesions complete surgical resection associated seizurefree outcome 80 100 casespmid33880269 pmcpmc8051422 doi107759 cureus13917,0.0
involvement cytotoxic eomesexpressing cd4 + t cells secondary progressive multiple sclerosis proc natl acad sci u s 2021 mar 16 118 11 e2021818118 doi 101073 pnas2021818118abstractmultiple sclerosis ms putative autoimmune disease central nervous system cns commonly presents relapsingremitting ms rrms characterized recurrent episodes peripheral disabling symptoms resulting inflammatory cns damage many rrms patients transition chronic disease course progressive neurological dysfunctions secondary progressive ms spms progression rate varying patients time spms pathogenesis now linked immunecellmediated processes although mechanisms driving spms transition progression remain elusive spms lacks biomarkers effective treatments report crucial involvement cytotoxic cd4+ t cells expressing eomes eomes+ th cells spms pathogenesisa th cell subset previously identified mouse model late chronic autoimmune cns inflammation eomes+ th cells circulate rrms patient peripheral blood n 44 primary progressive ms ppms patients n 25 healthy controls n 42 eomes+ th cells significantly increased spms n 105 p 00001 strikingly lymphocytes isolated spms autopsy brain samples revealed cd4+ t cells infiltrating cns coexpressed eomes cytotoxic molecule granzyme b particular eomes+ th cell levels increased spms patients progressive disease phases versus spms patients without current disability increases p 00001 moreover eomes level acted biomarker predict spms patients risk disease worsening 80 accuracy rocauc 08276 overall results indicate granzyme bexpressing eomes+ t helper cells involved pathogenesis spms significant implications spms biomarkers therapeutic targetspmid33836594 doi101073 pnas2021818118,0.0
chromatin regulator srg3 overexpression protects lps dgalninduced sepsis increasing il10producing macrophages decreasing ifnproducing nk cells liver int j mol sci 2021 mar 16 22 6 3043 doi 103390 ijms22063043abstractwe previously showed ubiquitous overexpression chromatin remodeling factor switch3related gene srg3 promotes m2 macrophage differentiation resulting antiinflammatory responses experimental autoimmune encephalomyelitis model multiple sclerosis since hepatic macrophages responsible sepsisinduced liver injury investigated herein capacity transgenic srg3 overexpression srg3actin mice modulate sepsis mice exposed lipopolysaccharide lps plus dgalactosamine dgaln results demonstrated ubiquitous srg3 overexpression significantly protects mice lps dgalninduced lethality mediated hepatic m1 macrophages protective effects srg3 overexpression correlated phenotypic conversion hepatic macrophages m1 toward m2 phenotype furthermore srg3actin mice decreased numbers activation natural killer nk cells natural killer t nkt cells liver sepsis indicating srg3 overexpression might contribute crosstalk nk cells macrophages liver finally demonstrated nkt celldeficient cd1d ko srg3actin mice protected lps dgalninduced sepsis indicating nkt cells dispensable srg3mediated sepsis suppression taken together findings provide strong evidence srg3 overexpression may serve therapeutic approach control overwhelming inflammatory diseases sepsispmid33809795 doi103390 ijms22063043,0.0
evolution brain volume loss rates early stages multiple sclerosis neurol neuroimmunol neuroinflamm 2021 mar 16 8 3 e979 doi 101212 nxi0000000000000979 print 2021 mayabstractobjective describe dynamics brain volume loss bvl different stages relapsingremitting multiple sclerosis rrms describe association bvl clinical measures investigate effect treatment escalation rate bvlmethods together 1903 patients predominantly rrms avonexsteroidsazathioprine cohort n 166 study early ifn1a treatment cohort n 180 quantitative mri cohort n 1 557 2 mri scans 1year followup included brain mri scans n 7 203 performed using single 15t machine relationships age disease duration global tissuespecific bvl rates analyzed using mixed modelsresults age associated rate bvl 0003 cohen f2 00005 adjusted p 039 although disease duration associated rate bvl effect bvl rate minimal 0012 cohen f2 0004 adjusted p 4 105 analysis association tissuespecific brain volume changes age 0019 0011 adjusted p 0028100 disease duration 0028 0008 adjusted p 016096 confirmed results although increase relapse rate 010 adjusted p 9 109 expanded disability status scale edss 017 adjusted p 8 105 edss change 015 adjusted p 2 105 associated accelerated rate bvl effect rate bvl minimal cohen f2 0007 94 patients escalated therapy rate bvl decreased following treatment escalation 029 029 cohen f2 0133 p 55 108 conclusions rate bvl relatively stable throughout course rrms accelerated bvl weakly associated concurrent higher disease activity timely escalation highefficacy immunotherapy helps decrease rate bvlpmid33727311 doi101212 nxi0000000000000979,0.0
systemic lupus erythematosus geomagnetic disturbances time series analysis background examine influence solar cycle geomagnetic effects sle disease activitymethodsthe data used analysis consisted 327 observations 27day physician global assessment pga averages january 1996 february 2020 considered geomagnetic indices ap index daily average level geomagnetic activity sunspot number index r measure area solar surface covered spots f107 index measure noise level generated sun wavelength 107 cm earths orbit au index upper auroral electrojet index high energy 60 mev proton flux events geomagnetic data obtained goddard space flight center space physics data facility time series decomposition pga averages performed first step linear relationships pga geomagnetic indices examined using parametric statistical methods pearson correlation linear regression nonlinear relationships examined using nonparametric statistical methods spearmans rho kernel regressionresultsafter time series deconstruction pga averages seasonality explained significant fraction variance time series r2 387 one cycle completed every 16 years analysis shortterm 27day relationships indicated increases geomagnetic activity ap index p 01 high energy proton fluxes 60 mev p 005 associated decreases sle disease activity increases sunspot number index r anticipated decreases sle disease activity expressed pga p 005 shortterm correlations became statistically insignificant adjusting multiple comparisons using bonferroni correction analysis longterm 297 day relationships indicated stronger negative association changes pga changes sunspot number index r p 001 ap index p 001 f107 index p 001 longterm correlations remained statistically significant adjusting multiple comparisons using bonferroni correctionconclusionthe seasonality pga averages one cycle every 16 years explains significant fraction variance time series geomagnetic disturbances including level geomagnetic activity sunspot numbers high proton flux events may influence sle disease activity studies geographic locales needed validate findings,0.0
sustained clinical improvement subset patients progressive multiple sclerosis treated epsteinbarr virusspecific t cell therapy front neurol 2021 mar 15 12652811 doi 103389 fneur2021652811 ecollection 2021abstractbackground increasing evidence indicates role epsteinbarr virus ebv pathogenesis multiple sclerosis ms ebvinfected autoreactive b cells might accumulate central nervous system defective cytotoxic cd8+ t cell immunity previously reported results phase clinical trial autologous ebvspecific t cell therapy ms 6 months treatment objective investigate longerterm outcomes ms patients received autologous ebvspecific t cell therapy methods assessed participants 2 3 years completion t cell therapy results collected data 10 treated participants year 2 9 participants year 3 serious treatmentrelated adverse events observed four participants least sustained clinical improvement year 2 including reduced fatigue three participants reduced expanded disability status scale score two participants three participants experienced sustained improvement least symptoms year 3 sustained improvement associated higher ebvspecific cd8+ t cell reactivity administered t cell product conclusion autologous ebvspecific t cell therapy welltolerated degree clinical improvement can sustained 3 years treatmentpmid33790852 pmcpmc8005645 doi103389 fneur2021652811,0.0
small compounds mimicking adhesion molecule l1 improve recovery zebrafish demyelination model sci rep 2021 mar 15 11 1 5878 doi 101038 s41598021854121abstractdemyelination leads loss neurons results among consequences severe reduction locomotor function underlies several diseases humans including multiple sclerosis polyneuropathies considerable clinical progress made counteracting demyelination however remains need novel methods reduce demyelination concomitantly achieving remyelination thus complementing currently available tools ameliorate demyelinating diseases study used established zebrafish demyelination model test selected compounds following screening cell culture experiments mouse model spinal cord injury aimed identifying beneficial functions neural cell adhesion molecule l1 comparison mammalian nervous system disease models zebrafish allows testing potentially promotive compounds easily possible mammals found selected compounds tacrine duloxetine significantly improved remyelination peripheral central nervous system transgenic zebrafish following pharmacologically induced demyelination given molecules known positively affect functions related l1 disease contexts propose combined beneficial function raises hope use compounds clinical settingspmid33723325 doi101038 s41598021854121,1.0
correlation osteoarthritis rheumatoid arthritis bone mineral density adults aged 2059 years background reported osteoporosis commonly occurs among patients rheumatoid arthritis ra whereas association osteoporosis osteoarthritis oa remains controversial aim study investigate association bmd marker osteoporosis oa ra among adults 2059 years age using populationbased sample national health nutrition examination survey nhanes methodsour analysis based nhanes data collected 2011 2018 data regarding arthritis status type arthritis oa ra obtained questionnaires lumbar bmd measured dualenergy xray absorptiometry association oa ra lumbar bmd evaluated using logistic regression models subgroup analyses stratified gender race performed association duration arthritis lumbar bmd also investigatedresultsa total 11 094 adults included study compared nonarthritis group participants oa higher lumbar bmd 0023 95 ci 00110035 significant association lumbar bmd ra 0014 95 ci 0003 0031 subgroup analyses stratified gender males oa higher lumbar bmd compared without oa 0047 95 ci 00280066 females oa associated lumbar bmd 0007 95 ci 0008 0021 association lumbar bmd ra males 0023 95 ci 0003 0048 females 0008 95 ci 0015 0031 duration arthritis associated lumbar bmd oa 00001 95 ci 00017 00015 ra 00006 95 ci 00012 00025 conclusionslumbar bmd associated oa ra higher lumbar bmd associated oa males females findings may improve understanding oa ra bone health,0.0
effector t helper cells selectively controlled pregnancy related postpartum relapse multiple sclerosis front immunol 2021 mar 15 12642038 doi 103389 fimmu2021642038 ecollection 2021abstractbackground multiple sclerosis ms patients protected relapses pregnancy increased relapse risk delivery unknown pregnancy controls diseasecontributing cd4+ t helper th cells whether differs ms patients experience postpartum relapse studied effector phenotype th cells relation pregnancy postpartum relapse occurrence ms methods memory skewing activation effector th subsets analyzed paired third trimester postpartum blood 19 ms patients without postpartum relapse 12 healthy controls ex vivo results associated circulating levels pregnancyinduced hormones mirrored vitro exposing proliferating th cells corresponding serum samples results based hsneguided analyses found effector memory proportions th cells increased postpartum vs third trimester samples ms patients without postpartum relapse seen relapsing patients healthy controls cxcr3 upregulated postpartum memory th cells except relapsing patients changes verified adding sera individuals proliferating th cells associate third trimester cortisol estradiol progesterone levels relapsing patients activated memory th cells third trimester postpartum samples produced higher levels proinflammatory cytokines conclusion effector th cells differentially regulated pregnancy ms patients likely via serumrelated factors beyond studied hormones proinflammatory state memory th cells pregnancy may predict postpartum relapsepmid33790911 pmcpmc8005718 doi103389 fimmu2021642038,0.0
redistributing illdefined causes death case study burden 2020project germany background cause death statistics germany include relatively high share 26 2017 illdefined deaths idd make use cause death statistics burden disease calculations redistribute idd valid causes deathmethodsthe process proportional redistribution described detail makes use distribution valid icdcodes cause death data use examples stroke diabetes heart failure illustrate idd reallocatedresultsthe largest increases number deaths women men found lower respiratory infections diabetes mellitus stroke numbers deaths causes doubled redistributionconclusionthis first comprehensive redistribution idd using german cause death statistics performing redistribution necessary burden disease analyses otherwise underreporting certain causes death large numbers deaths coded residual unspecific codes,0.0
postcovid19 encephalomyelitis abstractsince outbreak coronavirus disease 2019 covid19 growing number cases acute transverse myelitis associated covid19 reported present case patient developed sensory ataxia covid19 mr lesions suggestive longitudinal myelitis splenium corpus callosum patient successfully treated immunoadsorption,0.0
ultrasound nonultrasound imaging techniques assessment diaphragmatic dysfunction abstractdiaphragm muscle dysfunction increasingly recognized important element several diseases including neuromuscular disease chronic obstructive pulmonary disease diaphragm dysfunction critically ill patients functional evaluation diaphragm challenging use volitional maneuvers test diaphragm can limited patient effort nonvolitional tests using neuromuscular stimulation technically complex since muscle relatively inaccessible growing interest using imaging techniques characterize diaphragm muscle dysfunction selecting appropriate imaging technique given clinical scenario critical step evaluation patients suspected diaphragm dysfunction review aim present detailed analysis evidence use ultrasound nonultrasound imaging techniques assessment diaphragm dysfunction highlight utility qualitative information gathered ultrasound imaging means assess integrity excursion thickness thickening diaphragm contrast quantitative ultrasound analysis diaphragm marred inherent limitations technique provide detailed examination limitations evaluate nonultrasound imaging modalities apply static techniques chest radiograph computerized tomography magnetic resonance imaging used assess muscle position shape dimension also evaluate nonultrasound imaging modalities apply dynamic imaging fluoroscopy dynamic magnetic resonance imaging assess diaphragm motion finally critically review application techniques clinical setting diaphragm dysfunction suspected,0.0
intestinal mycobiota health diseases disrupted equilibrium clinical opportunities abstractbacteria viruses protozoa fungi establish complex ecosystem gut like microbiota gut mycobiota plays indispensable role modulating intestinal physiology notably striking characteristics intestinal fungi extraintestinal functions provide comprehensive review importance gut fungi regulation intestinal pulmonary hepatic renal pancreatic brain functions present possible opportunities application gut mycobiota alleviate treat human diseases video abstract,0.0
evaluation retinal layer thickness parameters biomarkers realworld multiple sclerosis cohort eye brain 2021 mar 12 135969 doi 102147 ebs295610 ecollection 2021abstractpurpose retinal layer thickness parameters measured optical coherence tomography oct emerging biomarkers neuroaxonal degeneration inflammation multiple sclerosis ms aimed evaluate value retinal layer thickness prediction disability worsening relapse realworld ms cohortpatients methods longitudinal observational study included ms patients spectraldomain oct scans available 1 year clinical followup value peripapillary retinal nerve fiber layer prnfl macular ganglioncellandinnerplexiformlayer gcipl inner nuclear layer inl thickness prediction disability worsening relapse observation period tested multivariate modelsresults analyzed 60 ms patients mean observation period 29 years sd 18 lower baseline thickness gcipl cutoff 77m hr 41 p0001 prnfl cutoff 88m hr 31 p0019 associated increased risk disability worsening longitudinally mean thinning rates 08m year sd 16 gcipl 06m year sd 35 prnfl gcipl thinning 10m year prnfl 15m year associated higher likelihood disability worsening hr 57 p0009 hr 68 p0003 respectively inl thickened patients relapse mean 09m thinning 03m patients without relapse p004 multivariate analyses inl thickening associated increased probability relapse 178 p0023 conclusion crosssectional longitudinal measurement gcipl prnfl thinning reliable biomarker disability worsening realworld setting change inl thickness promising marker relapse ie inflammatory activitypmid33737853 pmcpmc7966301 doi102147 ebs295610,0.0
mir21 nonspecific biomarker maladies abstractmirna21 among abundant highly conserved micrornas mirnas recognized expressed essentially cells performs vital regulatory roles health disease also frequently claimed biomarker diseases cancer heart disease bodilyfluid based mirna studies dissociate contributions cellular physiology pathology potential biomarker show claimed specific predictive prognostic biomarker least 29 diseases thus specificity one disease result considered viable candidate biomarker despite continued evaluation theme multiple assignments mirna biomarker shared common ubiquitous mirnas concerning well,0.0
capturing pathogenic immune cells home brain med n y 2021 mar 12 2 3 214216 doi 101016 jmedj202102005abstractin issue kaufmann colleagues1 describe population immune cells home brain multiple sclerosis ms using approved therapeutic targeting 41integrin demonstrated trap cells blood opening possibility elimination cross brainpmid33796875 pmcpmc8011039 doi101016 jmedj202102005,0.0
expanding spectrum movement disorders associated c9orf72 hexanucleotide expansions neurol genet 2021 mar 12 7 2 e575 doi 101212 nxg0000000000000575 ecollection 2021 aprabstractobjective hexanucleotide repeat expansions hres c9orf72 major cause frontotemporal dementia ftd amyotrophic lateral sclerosis als aimed determine frequency phenomenology movement disorders md carriers hre c9orf72 retrospective review patients medical recordsmethods retrospectively reviewed clinical records patients carrying c9orf72 hre pathogenic range compared characteristics patients without mdresults seventeen 40 patients c9orf72 hre documented md 6 17 md presenting symptom 2 17 md sole manifestation disease ftd present 13 17 patients als 5 17 patients 2 17 patients develop ftd als thirteen 17 patients one md common md parkinsonism tremor resembling essential tremor syndrome one present 11 17 patients distal stimulussensitive upper limbs myoclonus present 6 17 patients cervical dystonia 5 17 patients chorea present 5 17 patients 4 showed marked orofacial dyskinesias frequent md combination tremor parkinsonism observed 8 17 patients 5 also myoclonus c9orf72 patients without md shorter followup times higher proportion als although results survive correction multiple comparisonsconclusions md frequent c9orf72 may precede signs als ftd even present isolation parkinsonism tremor myoclonus commonly observedpmid33977144 pmcpmc8105892 doi101212 nxg0000000000000575,0.0
socs6 promotes radiosensitivity decreases cancer cell stemness esophageal squamous cell carcinoma regulating ckit ubiquitylation background radiotherapy major treatment esophageal squamous cell carcinoma escc however hpv infection related radioresistance caused poor prognosis escc function socs6 shown tumor suppressor several cancers fully investigated till now manuscript aim investigate role socs6 regulating escc radioresistancemethodsfiftyseven escc patients enrolled survival analysis socs6 stably overexpressed hpv+ escc escc cells cells treated radiation subjected colony formation assays expression dna damage repair regulating proteins examined western blotting cell growth cell migration cisplatin sensitivity analyzed sphere formation assays flow cytometry used investigate changes cancer stem cell csc properties immunofluorescent staining confocal microscopy used locate socs6 ckit ubiquitylation level ckit analyzed immunoprecipitation coimmunoprecipitation coip socs6 ckit performed vivo xenograft animal models treated radiation examine radiosensitivityresultssocs6 correlated better prognosis escc patients radioresistance impaired socs6 upregulation inhibited cell growth migration increased sensitivity cisplatin socs6 significantly decreased population cscs expressing surface biomarker cd271 cd24low cd44high ability sphere formation socs6 ckit collocated cytoplasm blotting ubiquitin coip experiments indicated mechanism related ubiquitylation degradation receptor ckit xenograft tumor mouse model showed socs6 inhibited tumor growth promoted radiosensitivity vivoconclusionsour findings suggest socs6 can promote radiosensitivity hpv+ escc escc cells reduce stemness via ubiquitylation degradation ckit thus socs6 potential target overcoming radioresistance escc,0.0
jcpyv mirj15p urine natalizumabtreated multiple sclerosis patients viruses 2021 mar 12 13 3 468 doi 103390 v13030468abstractthe use natalizumab multiple sclerosis ms can cause reactivation polyomavirus jc jcpyv may result development progressive multifocal leukoencephalopathy pml rare usually lethal disease jcpyv infection highly prevalent worldwide population detection antijcpyv antibodies sufficient identify jcpyv infection pml can develop even patients negative jcpyv serology better comprehension jcpyv biology allow better understanding jcpyv infection reactivation possibly reducing risk developing pml investigated whether jcpyv mirj15pa mirna downregulates early phase viral protein tantigen promotes viral latencycould detected quantified digital droplet pcr ddpcr urine 25 natalizumabtreated ms patients 24month study designed baseline first dose natalizumab 1 t1 12 t12 24 months t24 therapy mirj15p detected urine 7 25 ms patients 28 detection possible three cases t24 two cases t12 one case t1 t12 last case baseline t1 two patients seronegative jcpyv ab viral dna never found either urine blood note one case mirj15p detected initiation natalizumab results suggest measurement mirj15p urine biomarker monitor jcpyv infection better identify possible risk developing pml natalizumabtreated ms patientspmid33809082 doi103390 v13030468,0.0
isolated thoracic intramedullary erdheimchester disease presenting paraplegia case report literature review background erdheimchester disease ecd rare idiopathic systemic nonlangerhans cell histiocytosis involving long bone visceral organs central nervous system cns involvement uncommon cases develop part systemic disease present rare case variant ecd isolated intramedullary tumorcase presentationa 75yearold female patient medical history diabetes hypertension presented suddenonset flaccid paraparesis 1 day neurological examination revealed grade 23 weakness legs decreased deep tendon reflex loss anal tone numbness t4 leg weakness deteriorated g1 surgery preoperative magnetic resonance imaging mri 18ffluorodeoxyglucose positron emission tomography computed tomography fdgpet ct showed intramedullary mass lesion t2t4 systemic lesion heterogeneous enhancement pattern cord swelling edema c7 t6 gross total removal achieved whitegraycolored softnatured intramedullary mass lesion illdefined boundary histological finding revealed benign histiocytic proliferation foamy histiocytes uniform nuclei concluded isolated intramedullary ecd patient showed selfstanding walkable 18month evidence recurrence new lesion spine mri wholebody fdgpet ct sudden occurrence unknown originated thoracic cord infarctionconclusionswe experienced extremely rare case isolated intramedullary ecd controlled surgical resection adjuvant therapy histological examination important final diagnosis careful serial followup surgical resection required identify recurrence progression systemic disease,0.0
genetic molecular biology autism spectrum disorder among middle east population review background autism spectrum disorder asd neurodevelopmental disease characterized impaired social communication executive dysfunction abnormal perceptual processing frequent among males clinical manifestations associated atypical neural development various genetic environmental risk factors involved etiology autism genetic assessment essential early detection intervention can improve social communications reduce abnormal behaviors although noticeable asd incidence middle east countries still lack knowledge genetic molecular biology asd among population introduce efficient diagnostic prognostic methodsmain bodyin present review summarized genes associated asd progression among middle east population also categorized reported genes based cell molecular functionsconclusionsthis review clarifies genetic molecular biology asd among middle east population paves way introducing efficient population based panel genetic markers early detection management asd middle east countries,0.0
identification lncrnas associated pathogenesis ankylosing spondylitis background ankylosing spondylitis chronic autoimmune disease affecting sacroiliac joint date studies examined association long noncoding rnas lncrnas pathogenesis herein sought characterize patterns asrelated lncrna expression evaluate potential role played lncrnas complex autoimmune contextmethodswe conducted rnaseq analysis peripheral blood mononuclear cell pbmc samples isolated five patients corresponding controls data leveraged characterize asrelated lncrna expression patterns conducted go kegg enrichment analyses parental genes encoding lncrnas confirmed validity rnaseq data assessing expression six lncrnas via qrtpcr 15 control patient samples pearson correlation analyses additionally employed examine associations expression levels six lncrnas patient clinical index valuesresultswe detected 56 575 total lncrnas control patient samples initial rnaseq analysis 200 70 found downregulated fc 2 005 p 005 respectively samples relative controls qrtpcr validation assays confirmed significant upregulation nonhsat1188012 enst00000444046 nonhsat1838471 significant downregulation nonhsat2051101 nonhsat1054442 nonhsat0518562 patient samples found expression nonhsat1188012 nonhsat1838471 positively correlated disease severityconclusionoverall findings highlight several lncrnas specifically expressed pbmcs patients indicating may play key functions pathogenesis autoimmune disease specifically determined nonhsat1188012 nonhsat1838471 may influence occurrence development,0.0
analysis pi3k pathway associated molecules reveals dysregulated innate adaptive functions b cells early diffuse cutaneous systemic sclerosis int j mol sci 2021 mar 12 22 6 2877 doi 103390 ijms22062877abstractb cell activation early event development systemic sclerosis ssc classical activation b cells downstream bcell receptor bcr involves phosphatidylinositol3 kinase pi3k pathway integrates effects multiple costimulatory receptors analysis pi3k pathway associated molecules peripheral blood b cells early diffuse cutaneous ssc dcssc patients showed altered mrna expression tolllike receptor tlr homolog cd180 tlr4 complement component 3 il4 receptor secreted phosphoprotein 1 spp1 parallel found elevated basal spp1 secretion dcssc b cells bcr + il4 receptor costimulation induce secretion cd180 stimulation alone resulted nfb activation b cells cd180 + bcr costimulation dcssc healthy control hc coengagement increased phosphorylation nfb dcssc b cells additionally contrast hc b cells lower basal production il10 dcssc b cells elevated cd180 stimulation furthermore activation via cd180 increased percentage cd86+ switched memory cd27+igd b cells dcssc compared hc results suggest alternative b cell activation cd180 dysfunction cause imbalance regulatory mechanisms dcssc b cellspmid33809015 doi103390 ijms22062877,0.0
peritoneal dialysisassociated peritonitis caused mycobacteroides massiliense first case review literature background peritoneal dialysis pd associated peritonitis caused nontuberculous mycobacterium rare however number cases increased past decades mycobacteroides massiliense subspecies mycobacteroides abscessus complex different clinical characteristics compared subspecies complex previous case reports pdassociated peritonitis caused mycobacteroides abscessus complex distinguished subspecies detailcase presentationa 40yearold man presented exitsite tunnel infection refractory antibiotic therapy peritonitis occurred simultaneous catheter removal reinsertion mycobacteroides abscessus complex detected culture dialysis effluent removal pd catheter combined antibiotics including macrolides resulted good clinical course analysis multiplex pcr hsp65 gene sequence identified bacterium mycobacteroides massilienseconclusionsthe mycobacteroides abscessus complex classified three subspecies mycobacteroides abscessus mycobacteroides massiliense mycobacteroides bolletii different characteristics particularly antibiotic susceptibility therefore clear identification subspecies mycobacteroides abscessus complex necessary definitive treatment,0.0
identifying cnscolonizing t cells potential therapeutic targets prevent progression multiple sclerosis med n y 2021 mar 12 2 3 296312e8 doi 101016 jmedj202101006abstractbackground multiple sclerosis ms autoimmune disease central nervous system cns can suppressed early stages eventually becomes clinically progressive unresponsive therapy investigate whether therapeutic resistance progressive ms can attributed chronic immune cell accumulation behind bloodbrain barrier bbb methods systematically track cnshoming immune cells peripheral blood 31 ms patients 31 matched healthy individuals integrated analysis 497 705 singlecell transcriptomes 355 433 surface protein profiles 71 samples spatial rna sequencing localize cells post mortem brain tissue 6 progressive ms patients contrasted 4 control brains 20 samples 85 000 spot transcriptomes findings identify specific pathogenic cd161+ lymphotoxin beta ltb + t cell population resides brains progressive ms patients intriguingly data suggest colonization cns t cells may begin earlier disease course can mobilized blood usage integrinblocking antibody natalizumab relapsingremitting ms patientsconclusions consequence lay groundwork therapeutic strategy deplete cnshoming t cells can fuel treatmentresistant progressionfunding study supported funding university medical center hamburgeppendorf stifterverband fr die deutsche wissenschaft oak foundation medical research council uk wellcomepmid33748804 pmcpmc7966680 doi101016 jmedj202101006,0.0
prospects use cannabinoids psychiatric disorders front psychiatry 2021 mar 12 12620073 doi 103389 fpsyt2021620073 ecollection 2021abstractincreasing evidence suggests essential role endocannabinoid system modulating cognitive abilities mood stress sleep psychoactive effects cannabis described euphoric calming anxiolytic sleepinducing positively affect mood can also adversely affect therapy responses cannabinoid medications depend patients endocannabinoid system activity proportion phytocannabinoids terpenoid composition dose used evidence therapeutic use phytocannabinoids psychiatric conditions thc cbd may opposing effects anxiety current guidelines recommend caution using thc patients anxiety mood disorders small number clinical trials cannabinoids used treat cancer hiv multiple sclerosis hepatitis c crohns disease chronic neuropathic pain report decreases anxiety depression symptoms presented sedative anxiolytic effects several studies investigated influence potential genetic factors psychosis schizophrenia development cannabis use thc may increase risk psychosis especially young patients immature central nervous system limited evidence clinical trials cannabinoids effective therapy sleep disorders associated concomitant conditions evidence possible role cannabis substitute alcohol drugs also context risks opioid use eg opioidrelated mortality narrative review recent evidence discuss prospects using psychoactive effects cannabinoids treating mental psychiatric disorders however evidence weak clinical conditions welldesigned randomized controlled trials currently lacking furthermore disorders may worsened cannabis usepmid33776815 pmcpmc7994770 doi103389 fpsyt2021620073,0.0
multiple sclerosisassociated hnrnpa1 mutations alter hnrnpa1 dynamics influence stress granule formation int j mol sci 2021 mar 12 22 6 2909 doi 103390 ijms22062909abstractevidence indicates dysfunctional heterogeneous ribonucleoprotein a1 hnrnpa1 a1 contributes pathogenesis neurodegeneration multiple sclerosis understanding molecular mechanisms neurodegeneration multiple sclerosis may result novel therapies attenuate neurodegeneration thereby improving lives ms patients multiple sclerosis using vitro blue light induced optogenetic protein expression system containing optogene cryptochrome 2 fluorescent mcherry reporter examined effects multiple sclerosisassociated somatic a1 mutations p275s f281l a1 localization cluster kinetics stress granule formation realtime show a1 mutations caused cytoplasmic mislocalization significantly altered kinetics a1 cluster formation dissociation quantity size clusters a1 mutations also caused stress granule formation occur quickly frequently response blue light stimulation study establishes live cell optogenetics imaging system probe localization association characteristics a1 also demonstrates somatic mutations a1 alter function promote stress granule formation supports hypothesis a1 dysfunction may exacerbate neurodegeneration multiple sclerosispmid33809384 doi103390 ijms22062909,0.0
first phenotypic functional characterization placental extracellular vesicles women multiple sclerosis int j mol sci 2021 mar 12 22 6 2875 doi 103390 ijms22062875abstractpregnancy unique situation physiological immunomodulation well strong multiple sclerosis ms disease modulator whose mechanisms still unclear maternal decidua fetal trophoblast placental cells secrete extracellular vesicles evs known mediate cellular communication modulate maternal immune response contribution ms disease course pregnancy however unexplored provide first phenotypic functional characterization evs isolated cultures term placenta samples women ms differentiating decidua trophoblast particular analyzed expression profile 37 surface proteins tested functional role placental evs monocultures cd14+ monocytes cocultures cd4+ t regulatory t treg cells results indicated placental evs enriched surface markers typical stem progenitor cells conditioning evs samples women ms associated moderate decrease expression proinflammatory cytokines activated monocytes proliferation rate activated t cells cocultured tregs overall findings suggest immunomodulatory potential placental evs women ms set stage promising research field aiming elucidating role ms remissionpmid33809077 doi103390 ijms22062875,0.0
metaanalysis epidemiology giant cell arteritis across time space abstractintroductiongiant cell arteritis gca common large vessel vasculitis age 50 years metaanalysis examined geographical temporal distribution incidence prevalence mortality gcamethodsa systematic review conducted using embase scopus pubmed inceptions 2019 studies included reported least 50 gca patients defined location time frame articles mortality included standardized mortality ratio smr extracted possible mean pooled prevalence incidence smr calculated using random effects model linear regression used explore correlations latitude incidence prevalence mortalityresultsof 3569 citations identified 107 included pooled incidence gca 1000 922 1078 cases per 100 000 people 50 years old incidence highest scandinavia 2157 1890 2423 followed north south america 1089 878 1300 europe 726 605 847 oceania 785 148 1719 pooled prevalence 5174 4204 6143 cases per 100 000 people age 50 annual mortality 2044 1784 2303 deaths 1000 mortality generally decreased years publication p 00008 latitude correlated significantly incidence p 00011 prevalence mortalityconclusionsgca incidence varies nearly 3fold regions highest scandinavia significantly mortality may improving time,0.0
electroconvulsive therapy multiple sclerosis review current evidence prim care companion cns disord 2021 mar 11 23 2 20r02717 doi 104088 pcc20r02717abstractobjective review published literature last 5 years use electroconvulsive therapy ect multiple sclerosis ms focusing efficacy safety tolerability ms commonly neuropsychiatric comorbidity ect used ms severe lifethreatening forms mental illness treatment options failed rapid response requireddata sources englishlanguage literature published last 5 years january 2015june 2 2020 searched using terms ect electroconvulsive therapy shock therapy electroshock therapy electroconvulsive therapies multiple sclerosis chronic progressive multiple sclerosis acute relapsing multiple sclerosis multiple sclerosis relapsing remitting knowledgeshare national health service library application providing updates evidencebased practice used along embase psycinfo medline pubmed trip database offers complete updated list evidencebased online resources hdas healthcare databases advanced search crdweb centre reviews dissemination cochrane library reference lists articles identified search also reviewedstudy selection initial search revealed 30 articles potential relevance however individually evaluating articles 6 case studies 1 review article detailing use ect ms includeddata extraction studies analyzed authors obtain clinical information relevant meeting objectives reviewdata synthesis efficacy safety using ect ms derived case series case reports controlled trials systematic reviews evidence collated low qualityconclusions consensus ect effective treatment specific mental disorders ms including catatonia used ect successfully clinic patients ms however concerns potential effects ect neurologic cognitive function also possible risks using anesthetic agents particularly neuromuscular blockerspmid34000115 doi104088 pcc20r02717,0.0
interleukin19 abrogates experimental autoimmune encephalomyelitis attenuating antigenpresenting cell activation front immunol 2021 mar 11 12615898 doi 103389 fimmu2021615898 ecollection 2021abstractinterleukin19 il19 acts negativefeedback regulator limit proinflammatory response macrophages microglia autocrine paracrine manners various inflammatory diseases multiple sclerosis ms major neuroinflammatory disease central nervous system cns remains uncertain il19 contributes ms pathogenesis demonstrate il19 deficiency aggravates experimental autoimmune encephalomyelitis eae mouse model ms promoting il17producing helper t cell th17 cell infiltration cns addition il19deficient splenic macrophages expressed elevated levels major histocompatibility complex mhc class ii costimulatory molecules th17 cell differentiationassociated cytokines il1 il6 il23 tgf1 tnf observations indicated il19 plays critical role suppression ms pathogenesis inhibiting macrophage antigen presentation th17 cell expansion subsequent inflammatory responses furthermore treatment il19 significantly abrogated eae data suggest il19 provide significant therapeutic benefits patients mspmid33776998 pmcpmc7990911 doi103389 fimmu2021615898,0.0
fall prevention education people multiple sclerosis randomized clinical trial int j qual health care 2021 feb 26mzab035 doi 101093 intqhc mzab035 online ahead printabstractbackground online spaced education ose method recognized promoting longterm knowledge retention changing behaviors improving outcomes students healthcare professionals however little evidence impacts patient education aim research compare knowledge retention using educational brochure ose individuals multiple sclerosis ms verify impact educational methods fall outcomemethods individuals ms n230 randomly assigned two types patient education educational brochure control ose intervention 12 weeks intervention group received multiple choice tests fall prevention knowledge retention behavior change fall incidence assessed intervention three six months participants satisfaction education method also evaluatedresults knowledge retention similar groups behavior change observed groups significant reduction fall rate intervention group 060 027 six months p0001 participants satisfaction achieved average 875 differences groupsconclusion individuals demonstrated significant improvement fall rate outcome groups significant difference regard test scores satisfaction results similar groupspmid33638988 doi101093 intqhc mzab035,0.0
perceived impact multiple sclerosis selfmanagement mediating role coping strategies plos one 2021 mar 11 16 3 e0248135 doi 101371 journalpone0248135 ecollection 2021abstractlow level selfmanagement people multiple sclerosis ms considered predominant factor leads poor rehabilitation efficacy studies focusing relationship selfmanagement psychological variables can modified contribute expanding knowledge needed propose interventional programs aiming patient activation study aimed analyze whether coping strategies play mediating role association perceived impact ms level selfmanagement people ms crosssectional study included 382 people ms participants completed multiple sclerosis selfmanagement scalerevised multiple sclerosis impact scale29 coping inventory stressful situations study hypothesis evaluated using mediation analysis strobe checklist specifically prepared crosssectional research applied study reporting results indicate emotion problemfocused strategies coping can treated mediating association ms impact level selfmanagement people ms negative relationship found perceived ms impact problemoriented coping positive relationship found problemoriented coping selfmanagement furthermore positive relationship found ms impact emotionoriented coping negative relationship found emotionoriented coping selfmanagement indirect role avoidanceoriented coping significant study confirms role played coping strategies individuals selfmanagement ms selfmanagement determined perceived ms impact can controlled decreasing emotionalcoping increasing problemcoping strategies study imparts new knowledge regarding potential interventions improving level selfmanagement people ms indicates recognition individuals illness perceptions well maladaptive coping strategies can help health professionals identify might lower level selfmanagementpmid33705470 doi101371 journalpone0248135,0.0
uk prevalence underlying conditions increase risk severe covid19 disease point prevalence study using electronic health records background characterising size distribution population risk severe covid19 vital effective policy planning older age underlying health conditions associated higher risk death covid19 study aimed describe population risk severe covid19 due underlying health conditions across united kingdommethodswe used anonymised electronic health records clinical practice research datalink gold estimate point prevalence 5 march 2019 atrisk population following national guidance prevalence risk condition individual condition given overall stratified age region binomial exact confidence intervals repeated analysis 5 march 2014 full regional representation describe prevalence underlying health conditions pregnancy additionally described population cancer survivors assessed value linked secondary care records ascertaining covid19 atrisk statusresultson 5 march 2019 244 uk population risk due record least one underlying health condition including 83 schoolaged children 196 workingaged adults 662 individuals aged 70 years 71 population multimorbidity size atrisk population stable time comparing 2014 2019 despite increases chronic liver disease diabetes decreases chronic kidney disease current asthma separately 16 population new diagnosis cancer past 5 yconclusionsthe population risk severe covid19 defined either aged 70 years younger underlying health condition comprises 185 million individuals uk including considerable proportion schoolaged workingaged individuals national estimates broadly support use global burden disease modelled estimates countries provide age region stratified prevalence condition support effective modelling public health interventions planning vaccine resource allocation high prevalence health conditions among older age groups suggests agetargeted vaccination strategies may efficiently target individuals higher risk severe covid19,0.0
comparative analysis btk inhibitors mechanisms underlying adverse effects front cell dev biol 2021 mar 11 9630942 doi 103389 fcell2021630942 ecollection 2021abstractthe cytoplasmic proteintyrosine kinase btk plays essential role differentiation survival blineage cells hence represents suitable drug target number btk inhibitors btkis clinic increased considerably currently amounts least 22 firstinclass ibrutinib irreversible binder forming covalent bond cysteine catalytic region kinase identified 228 active trials listed clinicaltrialsgov nextgeneration inhibitors acalabrutinib zanubrutinib approved united states europe zanubrutinib also china tirabrutinib currently registered japan cases compounds used treatment blymphocyte tumors however increasing number trials instead addresses autoimmunity inflammation multiple sclerosis rheumatoid arthritis pemphigus systemic lupus erythematosus use either irreversibly binding inhibitors eg evobrutinib tolebrutinib reversibly binding inhibitors like fenebrutinib adverse effects aes predominantly implicated inhibition kinases btkibinding cysteine catalytic domain analysis reported aes suggests ibrutinibassociated atrial fibrillation caused binding erbb2 her2 erbb4 her4 however binding pattern btkis various additional kinases correlate common assumption skin manifestations diarrhoeas offtarget effects related egf receptor inhibition moreover dermatological toxicities diarrhoea bleedings invasive fungal infections often develop early btki treatment initiation subsequently subside conversely cardiovascular aes like hypertension various forms heart disease often persistpmid33777941 pmcpmc7991787 doi103389 fcell2021630942,0.0
exploratory factor analysis promis29 v10 promis global health rand sf36 chiropractic responders attending care practicebased research network background sf36 questionnaire perhaps widely used quality life instrument world today promis instruments continue gain popularity given continued use chiropractic research practice examined latent domain structure using exploratory factor analysis efa methodsto uncover latent structures large series measured variables promis29 promis global health rand sf36 domains defined factor analysis model represented equation x mu + lambda f +epsilon x x_ 1 ldots x_ p t matrix random vectors corresponding domains mean mu covariance matrix sigma lambda l_ jk _ pxm denotes matrix factor loadings f f_ 1 ldots f_ m t denotes matrix unobserved latent variables influence collection domains epsilon _ 1 ldots _ p t vector latent error terms matrix item responses x observed quantity restrictions variable scores uncorrelated unit variance latent errors independent variance vector psi inherited structure x expressed simply sigma lambda lambda t + psi orthogonal oblique rotations performed lambda matrix equation improve clarity latent structure model parameters left mu lambda psi right optimized using method minimum residuals efa model constructed pearson polychoric correlationresultsfor promis29 domains confirmed strongly correlated factor 1 ie mental health factor 2 ie physical health satisfaction participation social roles highly correlated 3rd factor ie social health promis global health scale 2factor efa confirmed gph gmh domains rand sf36 apparent lack definable structure observed except physical function high correlational relationship factor 2 remaining domains lacked correlation factorsconclusiondistinct separation latent factors presumed physical mental social health domains found promis instruments relatively indistinguishable domains rand sf36 encourage continued efforts area research improving patient reported outcomes,0.0
identification novel myelin repair drugs modulation oligodendroglial differentiation competence abstractbackgroundin multiple sclerosis loss myelin oligodendrocytes impairs saltatory signal transduction leads neuronal loss functional deficits limited capacity oligodendroglial precursor cells differentiate mature cells main reason inefficient myelin repair central nervous system drug repurposing constitutes powerful approach identification pharmacological compounds promoting processmethodsa phenotypic compound screening using subcellular distribution potent inhibitor oligodendroglial cell differentiation namely p57kip2 differentiation competence marker conducted hit compounds validated terms impact developmental cell differentiation myelination using rat human primary cell cultures organotypic cerebellar slice cultures respectively effect spontaneous remyelination investigated following cuprizonemediated demyelination corpus callosumfindingsa number novel small molecules able promote oligodendroglial cell differentiation identified subset found foster human oligodendrogenesis well myelination ex vivo among steroid danazol anthelminthic parbendazole found increase myelin repairinterpretationwe provide evidence early cellular processes involved differentiation decisions applicable identification regeneration promoting drugs suggest danazol parbendazole potent therapeutic candidates demyelinating diseasesfundingthis work supported jrgen manchot foundation dsseldorf research commission medical faculty heinrichheineuniversity dsseldorf christiane claudia hempel foundation stifterverband novartisstiftung james elisabeth cloppenburg peek cloppenburg dsseldorf stiftung international progressive ms alliance braveinms,1.0
immune soluble factors cerebrospinal fluid progressive multiple sclerosis patients segregate two groups front immunol 2021 mar 10 12633167 doi 103389 fimmu2021633167 ecollection 2021abstractprimaryprogressive pp secondaryprogressive sp multiple sclerosis ms characterized neurological deficits caused permanent neuronal damage clinically quantified expanded disability status scale edss neuronal tissue damage also mediated immune infiltrates producing soluble factors cytokines chemokines released cerebrospinal fluid csf mechanisms regulating production soluble factor completely defined using multiplex beadbased assays simultaneously measured 27 immune soluble factors csf collected 38 patients 26 ppms 12 spms performed correlation matrix soluble factors expressed csf csf patients ppms spms similar levels cytokines chemokines however stratification patients according active inactive magnetic resonance imaging mri unveils differences correlative studies soluble factors csf patients ppms spms revealed two clusters immune mediators proinflammatory functions namely ifn mcp1 mip1 mip1 il8 ip10 tnf group 1 antiinflammatory functions namely il9 il15 vegf il1ra group 2 however significant correlations cytokines group 1 group 2 lost patients severe disability edss 4 compared patients mild moderate disability edss 4 results suggest common regulation cytokines chemokines belonging group indicate patients severe disability production factors less coordinated possibly due advanced neurodegenerative mechanisms interfere immune responsepmid33777018 pmcpmc7988186 doi103389 fimmu2021633167,0.0
normal levels kif5 reduced klc1 levels alzheimer disease alzheimer disease syndrome evidence suggesting defects anterograde transport background impaired axonal transport may contribute pathogenesis neurodegenerative diseases including alzheimers disease ad syndrome ds axonal transport complex process specific motor proteins move cargoes neuronal cell bodies processes inconsistent reports point changes ad levels classical anterograde motor protein kinesin family member 5 kif5 primary neuronal kif regulator kinesin light chain 1 klc1 raising possibility anterograde transport compromised admethods materialsto address inconsistencies determine shared pathologies ad elderly ds subjects dementia ad ds adds extend changes kif5 klc1 measured levels three kif5 family members klc1 ad adds frontal cortex ad temporal cortex cerebellum samples taken short postmortem interval support future studies explore cell biological basis changes detected also examined levels proteins brains young aged adult mice dp 16 1yey + dp16 mouse model ds j20 mouse model adresultsthere changes comparison controls kif5 family members either ad adds samples normalized either actin glyceraldehyde3phosphate dehydrogenase gapdh interestingly however samples control brains well ad adds demonstrated strong positive correlations levels kif5 family members suggesting positive coregulated expression importantly earlier reports pointed negative correlation levels amyloid precursor protein app kif5a levels found opposite true adds especially striking given triplication app gene increased app protein levels ad control samples showed positive correlations flhapp kif5 members less consistent contrast findings kif5 levels klc1 downregulated frontal cortex ad adds brains interestingly change seen ad temporal cortex cerebellum postmortem interval negative effect levels klc1 kif5 members analyzed subset samples short postmortem interval pmi 6 h pmi significantly correlated levels klc1 either ad adds samples confirmed presence statistically significant reduction klc1 ad adds brains compared control brains studies comparing dp16 euploid control recapitulated human studies demonstrating change kif5 levels positive correlation levels kif5 family members j20 mice also showed normal kif5 levels however unlike ad adds frontal cortex klc1 levels reduced brains dp16 j20 miceconclusionthese data point significant reductions klc1 ad adds raise possibility compromised klc1mediated axonal transport conditions posit can now pursued model systems klc1 expression reduced,0.0
tdp43 maximizes nerve conduction velocity repressing cryptic exon paranodal junction assembly schwann cells elife 2021 mar 10 10e64456 doi 107554 elife64456abstracttdp43 extensively studied neurons physiological pathological contexts however emerging evidence indicates glial cells also reliant tdp43 function demonstrate deletion tdp43 schwann cells results dramatic delay peripheral nerve conduction causing significant motor deficits mice directly attributed absence paranodal axoglial junctions contrast paranodes central nervous system unaltered oligodendrocytes lacking tdp43 mechanistically tdp43 binds directly neurofascin mrna encoding cell adhesion molecule essential paranode assembly maintenance loss tdp43 triggers retention previously unidentified cryptic exon targets neurofascin mrna nonsensemediated decay thus tdp43 required neurofascin expression proper assembly maintenance paranodes rapid saltatory conduction findings provide framework mechanism schwann cellautonomous dysfunction nerve conduction directly caused tdp43 lossoffunctionpmid33689679 doi107554 elife64456,0.0
integrative genomic expression analysis reveals stable differences lung cancer systemic sclerosis background incidence mortality lung cancer highest among cancers patients systemic sclerosis show fourfold greater risk lung cancer general population however underlying mechanism remains poorly understoodmethodsthe expression profiles 355 peripheral blood samples integratedly analyzed including 70 cases lung cancer 61 cases systemic sclerosis 224 healthy controls data normalization cleaning differentially expressed genes degs disease control obtained deeply analyzed bioinformatics methods gene ontology go kyoto encyclopedia genes genomes kegg pathway enrichment analysis performed online david kobas proteinprotein interaction ppi networks constructed string databaseresultsfrom total 14 191 human genes 299 1644 genes identified degs systemic sclerosis lung cancer respectively among 64 degs overlapping including 36 coupregulated 10 codownregulated 18 counterregulated degs functional enrichment analysis showed two diseases common changes immunerelated genes expression innate immune response response virusrelated genes increased significantly expression negative regulation cell cyclerelated genes decreased notably contrast expression mitophagy regulation chromatin binding fatty acid metabolismrelated genes showed distinct trendsconclusionsstable differences similarities systemic sclerosis lung cancer revealed peripheral blood enhanced innate immunity weakened negative regulation cell cycle may common mechanisms two diseases may associated high risk lung cancer systemic sclerosis patients hand counterregulated degs can used novelbiomarkers pulmonary diseases addition fat metabolismrelated degs consideredto associated clinical blood lipid data,0.0
reducing posttraumatic stress parents patients rare inherited metabolic disorder using eye movement desensitization reprocessing therapy case study abstractparents children severe inborn errors metabolism frequently face stressful events related disease child consequently high risk developing parental posttraumatic stress disorder ptsd assessment subsequent treatment ptsd parents however common clinical practice ptsd can effectively treated eye movement desensitization reprocessing emdr however studies conducted yet regarding effect emdr parental ptsd emdr generally offered multiple weekly sessions may preclude participation parents generally overburdened ongoing often intensive care child therefore offered timelimited emdr maximum four sessions two subsequent days two parents mucopolysaccharidosis type iii mps iii patients explore potential effects qualitative quantitative outcomes used evaluate treatment effects parents felt resilient competent face future difficulties related disease child adverse effects reported quantitative outcomes showed clinically significant decrease post traumatic stress symptoms comorbid psychological distress pre post treatment beneficial effects maintained followup conclusion timelimited emdr may highly relevant treatment traumatized parents children mps iii probably also parents children rare progressive disorders research needed validate efficacy emdr specific population,0.0
il17 deficiency aggravates streptozotocininduced diabetic nephropathy reduction autophagosome formation mice background diabetic nephropathy dn one important medical complications diabetes mellitus autophagy important mediator pathological response plays critical role inflammation progression diabetic nephropathy interleukin il 17a favorably modulates inflammatory disorders including dn study examined whether il17a deficiency affected autophagy process kidneys mice streptozotocin stz induced dnmethodsthe autophagic response il17a stzinduced nephrotoxicity evaluated analyzing stzinduced functional histological renal injury il17a knockout ko miceresultsil17a ko stztreated mice developed severe nephropathy stztreated wildtype wt mice increased glomerular damage renal interstitial fibrosis 12 weeks il17a deficiency also increased upregulation proinflammatory cytokines fibrotic gene expression stz treatment meanwhile autophagyassociated proteins induced stztreated wt mice however il17a ko stztreated mice displayed significant decrease protein expression especially levels lc3 atg7 play crucial roles autophagosome formation notably decreased il17a ko stztreated mice compared wt counterpartsconclusionsil17 deficiency aggravates stzinduced dn via attenuation autophagic response study demonstrated il17a mediates stzinduced renal damage represents potential therapeutic target dn,0.0
gut microbial dysbiosis traumatic brain injury modulates immune response impairs neurogenesis abstractthe influence gut microbiota traumatic brain injury tbi presently unknown knowledge gap paramount clinical significance tbi patients highly susceptible alterations gut microbiota antibiotic exposure antibioticinduced gut microbial dysbiosis established prior tbi significantly worsened neuronal loss reduced microglia activation injured hippocampus concomitant changes fear memory response importantly antibiotic exposure 1 week tbi reduced cortical infiltration ly6chigh monocytes increased microglial proinflammatory markers decreased t lymphocyte infiltration persisted 1 month postinjury moreover microbial dysbiosis associated reduced neurogenesis dentate gyrus 1 week tbi 3 months injury 11 weeks discontinuation antibiotics observed increased microglial proliferation increased hippocampal neuronal loss modulation fear memory response data demonstrate antibioticinduced gut microbial dysbiosis tbi impacts neuroinflammation neurogenesis fear memory implicate gut microbial modulation potential therapeutic intervention tbi,0.0
insomnia neurological diseases abstractinsomnia defined difficulties initiating maintaining sleep early awakening poor subjective sleep quality despite adequate opportunity circumstances sleep impairment daytime performance components insomnia namely persistent sleep difficulties despite adequate sleep opportunity resulting daytime dysfunction appear secondary comorbid neurological diseases comorbid insomnia originates neurodegenerative inflammatory traumatic ischemic changes sleep regulating brainstem hypothalamic nuclei consecutive changes neurotransmitters symptoms neurological disorders ie motor deficits comorbidities ie pain depression anxiety diseasespecific pharmaceuticals may cause insomnia sleep problemsthis guideline focuses insomnias headaches neurodegenerative movement disorders multiple sclerosis traumatic brain injury epilepsies stroke neuromuscular disease dementiathe important new recommendations cognitive behavioral therapy cbti recommended treat acute chronic insomnia headache patients insomnia one frequent sleep complaints neurodegenerative movement disorders patients may benefit cbti antidepressants trazodone doxepin melatonin gabaagonists insomnia frequent precursor ms symptoms 10 years cbti recommended patients ms traumatic brain injury melatonin may improve insomnia symptoms children epilepsies patients insomnia stroke can treated benzodiazepine receptor agonists sedating antidepressants patients dementia suffering insomnia trazodone light therapy physical exercise recommended,0.0
heparanomemediated rescue oligodendrocyte progenitor quiescence following inflammatory demyelination proinflammatory cytokine ifn chronically elevated multiple sclerosis induces pathologic quiescence human oligodendrocyte progenitor cells opcs via upregulation transcription factor prrx1 study using animals sexes investigated role heparan sulfate proteoglycans modulation ifn signaling following demyelination found ifn profoundly impaired opc proliferation recruitment following adult spinal cord demyelination ifninduced quiescence mediated direct signaling opcs conditional genetic ablation ifnr1 ifngr1 adult ng2+ opcs completely abrogated inhibitory effects intriguingly opcspecific ifn signaling contributed failed oligodendrocyte differentiation associated hyperactive wnt bmp target gene expression opcs found pi88 heparan sulfate mimetic directly antagonized ifn rescue human opc proliferation differentiation vitro blocked ifnmediated inhibitory effects opc recruitment vivo importantly heparanase modulation pi88 ogt2155 demyelinated lesions rescued ifnmediated axonal damage demyelination addition opcspecific effects ifnaugmented lesions characterized increased size reactive astrogliosis proinflammatory microglial macrophage activation along exacerbated axonal injury cell death heparanase inhibitor treatment rescued many negative ifninduced sequelae suggesting profound modulation lesion environment together results suggest modulation heparanome represents rational approach mitigate negative effects proinflammatory signaling rescuing pathologic quiescence inflamed demyelinated human brainsignificance statement failure remyelination multiple sclerosis contributes neurologic dysfunction neurodegeneration activation proliferation oligodendrocyte progenitor cells opcs necessary step recruitment phase remyelination show proinflammatory cytokine interferon directly acts opcs induce pathologic quiescence thereby limit recruitment following demyelination heparan sulfate highly structured sulfated carbohydrate polymer present cell surface regulates several aspects signaling microenvironment find pathologic interferon can blocked modulation heparanome following demyelination using either heparan mimetic treatment heparanase inhibitor studies establish potential modulation heparanome regenerative approach demyelinating disease,1.0
ufiber leukoencephalopathy due novel mutation taco1 gene neurol genet 2021 mar 9 7 2 e573 doi 101212 nxg0000000000000573 ecollection 2021 aprno abstractpmid33709035 pmcpmc7943219 doi101212 nxg0000000000000573,0.0
alterations gut microbiota metabolite profiles context neuropathic pain abstractthe aim study explore relationships among gut microbiota disturbances serum spinal cord metabolic disorders neuropathic pain 16s rdna amplicon sequencing serum spinal cord metabolomics used identify alterations microbiota metabolite profiles sham rats chronic constriction injury cci model rats correlations abundances gut microbiota components genus level levels serum metabolites painrelated behavioural parameters analysed ingenuity pathway analysis ipa applied analyse interaction networks differentially expressed serum metabolites first found composition gut microbiota different rats cciinduced neuropathic pain sham controls genus level abundances helicobacter phascolarctobacterium christensenella blautia streptococcus rothia lactobacillus significantly increased whereas abundances ignatzschineria butyricimonas escherichia af12 corynebacterium significantly decreased additionally 72 significantly differentially expressed serum metabolites 17 significantly differentially expressed spinal cord metabolites identified cci rats sham rats finally correlation analysis showed changes gut microbiota significantly correlated changes serum metabolite levels suggesting dysbiosis gut microbiota important factor modulating metabolic disturbances context neuropathic pain conclusion research provides novel perspective potential roles gut microbiota related metabolites neuropathic pain,0.0
assessing measurement invariance 10item centre epidemiological studies depression scale beck anxiety inventory questionnaires across people living hiv aids healthy people background recently extensive research reported higher rate depression anxiety among people living hiv aids plwhas compared general population however single study carried investigate whether disparity real difference happens due lack measurement invariance study aims assess measurement invariance beck anxiety inventory bai 10item centre epidemiological studies depression scale cesd10 questionnaires across plwhas healthy individualsmethodsone hundred fifty plwhas 500 healthy individuals filled persian version bai cesd10 questionnaires multigroup multipleindicators multiplecauses model mgmimic used assess measurement invariance across plwhas healthy peopleresultsour findings revealed plwhas healthy individuals perceived meaning items bai cesd10 questionnaires similarly addition although depression scores significantly higher plwhas opposed healthy individuals significant difference observed anxiety scores two groupsconclusionsthe current study suggests bai cesd10 invariant measures across plwhas healthy people can used meaningful crossgroup comparison therefore comparison healthy individuals higher depression score plwhas real difference highly recommended health professionals develop therapeutic interventions psychological supports promote mental health plwhas alleviate depressive symptoms,0.0
early prediction putamen imaging features hivassociated neurocognitive impairment syndrome background explore correlation volume putamen brain cognitive impairment patients hiv predict feasibility earlystage hiv brain cognitive impairment radiomicsmethodretrospective selection 90 patients hiv infection including 36 asymptomatic neurocognitive impairment ani patients 54 preclinical ani patients beijing youan hospital patients received comprehensive neuropsychological assessment mri scanning 3d slicer software used acquire volume interest voi radiomics features clinical variables volume putamen compared patients ani preclinical ani kruskal wallis test used analysis multiple comparisons groups relationship cognitive scores voi compared using linear regression radiomics principal component analysis pca used reduce model overfitting calculations support vector machine svm used build binary classification model model performance evaluation used accuracy sensitivity specificity receiver operating characteristic curve roc resultthere significant differences clinical variables ani group preclinicalani group p005 volume bilateral putamen significantly different ahi group preclinical group p005 trend left putamen anitreatment group preclinical treatment group p 0063 reduced cognitive scores verbal fluency attention working memory executive functioning memory speed information processing negatively correlated increased voi p005 correlation relatively low diagnosing ani preclinical ani mean area roc curves auc 085 022 mean sensitivity specificity 6312 551 9425 308conclusionthe volumes putamen patients ani may larger patients preclinical ani change volume putamen may certain process relationship putamen cognitive impairment exact mechanism unclear radiomics may useful tool predicting early stage hand patients hiv,0.0
multiple sclerosis risk gene mertk required microglial activation subsequent remyelination cell rep 2021 mar 9 34 10 108835 doi 101016 jcelrep2021108835abstractin multiple sclerosis ms neurological diseases failure repair demyelinated lesions contributes axonal damage clinical disability provide evidence mertk gene highly expressed microglia alters ms risk required efficient remyelination compared wildtype wt mice mertkknockout ko mice show impaired clearance myelin debris remyelination following demyelination using singlecell rna sequencing characterize mertkinfluenced responses cuprizonemediated demyelination remyelination across different cell types mertkko brains show attenuated microglial response demyelination elevated proportion interferon ifn responsive microglia addition identify transcriptionally distinct subtype surviving oligodendrocytes specific demyelinated lesions inhibitory effect myelin debris remyelination mediated part ifn impedes microglial clearance myelin debris inhibits oligodendrocyte differentiation together work establishes role mertk microglia activation phagocytosis migration remyelinationpmid33691116 doi101016 jcelrep2021108835,1.0
itaconate confers tolerance late nlrp3 inflammasome activation cell rep 2021 mar 9 34 10 108756 doi 101016 jcelrep2021108756abstractitaconate unique regulatory metabolite induced upon tolllike receptor tlr stimulation myeloid cells demonstrate major inflammatory tolerance cell death phenotypes associated itaconate production activated macrophages show endogenous itaconate key regulator signal 2 nlr family pyrin domain containing 3 nlrp3 inflammasome activation long lipopolysaccharide lps priming establishes tolerance late nlrp3 inflammasome activation show itaconate acts synergistically inducible nitric oxide synthase inos ability various tlr ligands establish nlrp3 inflammasome tolerance depends pattern coexpression irg1 inos mechanistically itaconate accumulation upon prolonged inflammatory stimulation prevents full caspase1 activation processing gasdermin d demonstrate posttranslationally modified endogenous itaconate altogether data demonstrate metabolic rewiring inflammatory macrophages establishes tolerance nlrp3 inflammasome activation uncontrolled can result pyroptotic cell death tissue damagepmid33691097 doi101016 jcelrep2021108756,0.0
male sex chromosomal complement exacerbates pathogenicity th17 cells chronic model central nervous system autoimmunity cell rep 2021 mar 9 34 10 108833 doi 101016 jcelrep2021108833abstractsex differences multiple sclerosis ms incidence severity long recognized however underlying cellular molecular mechanisms male sex associated aggressive disease remain poorly defined using t cell adoptive transfer model chronic experimental autoimmune encephalomyelitis eae find male th17 cells induce disease increased severity relative female th17 cells irrespective whether transferred male female recipients throughout disease course greater frequency male th17 cells produce ifn hallmark pathogenic th17 responses intriguingly xy chromosomal complement increases pathogenicity male th17 cells xlinked immune regulator jarid1c downregulated pathogenic male murine th17 cells functional experiments reveal represses severity th17mediated eae furthermore jarid1c expression downregulated cd4+ t cells msaffected individuals data indicate male sex chromosomal complement critically regulates th17 cell pathogenicitypmid33691111 doi101016 jcelrep2021108833,0.0
altered iron myelin premanifest huntington#39 s disease 20 years clinical onset evidence crosssectional hd young adult study abstractbackgroundpathological processes huntingtonnulls disease hd begin many years prior symptom onset recently demonstrated premanifest cohort approximately 24 years predicted disease onset despite intact function evidence subtle neurodegeneration use novel imaging techniques determine whether macro microstructural changes can detected across wholebrain cohortmethods62 premanifest hd prehd 61 controls hd young adult study hdyas included grey white matter volume diffusion weighted imaging dwi measures white matter microstructure multiparametric maps mpm estimating myelin iron content magnetization transfer mt proton density pd longitudinal relaxation r1 effective transverse relaxation r2 myelin gratio examined group differences prehd controls assessed associations imaging metrics disease burden csf neurofilament light nfl also performed volumetric mpm results corrected clusterwise value familywise error fwe 005 diffusion gratio results corrected via thresholdfree cluster enhancement fwe 005findingswe showed significantly increased r1 r2 suggestive increased iron putamen globus pallidum external capsule prehd participants also significant association lower cortical r2 suggestive reduced myelin iron higher csf nfl frontal lobe parietooccipital cortices results significant corrected levelsinterpretationincreased iron subcortical structures surrounding white matter feature early prehd furthermore increases csf nfl linked microstructural changes posterior parietaloccipital cortex region previously shown undergo earliest cortical changes hd findings suggest disease related process occurring subcortical cortical regions 20 years predicted disease onset,1.0
editorial vitamin d neurological diseases pathophysiology therapy front neurol 2021 mar 9 12614900 doi 103389 fneur2021614900 ecollection 2021no abstractpmid33767657 pmcpmc7985255 doi103389 fneur2021614900,0.0
identification 11 candidate structured noncoding rna motifs humans comparative genomics background 15 human genome encodes proteins large part remaining encodes noncoding rnas ncrna many ncrnas form structures perform many important functions accurately identifying structured ncrnas human genome discovering biological functions remain major challengeresultshere established pipeline cmline following features analyzing large genomes humans animals first selected species larger genetic distances facilitate discovery covariations compatible mutations second used cmfinder can generate useful alignments even low sequence conservation third removed repetitive sequences known structured ncrnas reduce workload cmfinder fourth used infernal find representatives refine structure reported 11 classes structured ncrna candidates significant covariations humans functional analysis showed ncrnas may variable functions may regulate circadian clock genes poly signals pas may regulate elongation factor eef1a tcell receptor signaling pathway cooperating rna binding proteinsconclusionsby searching important features rna structure large genomes cmline revealed existence variety novel structured ncrnas functional analysis suggests newly discovered ncrna motifs may biological functions pipeline established discovery structured ncrnas identification functions can also applied analyze large genomes,0.0
incidence risk infection associated fingolimod patients multiple sclerosis systematic review metaanalysis 8 448 patients 12 randomized controlled trials front immunol 2021 mar 8 12611711 doi 103389 fimmu2021611711 ecollection 2021abstractbackground aims controversy regarding whether fingolimod associated increased risk infection patients multiple sclerosis ms performed systematic review metaanalysis data randomized controlled trials rcts determine risk infection patients methods systematically searched pubmed embase cochrane library clinicaltrialsgov inception april 8 2020 identify rcts reported occurrence infection patients ms treated fingolimod relative risks rrs 95 confidence intervals 95 cis calculated using randomeffects model results twelve rcts including 8 448 patients eligible compared control placebo active treatments fingolimod significantly increased risk infection rr 116 95 ci 107127 2 81 regardless whether infection general infection rr 114 95 ci 105125 2 78 serious infection rr 149 95 ci 106210 2 0 analyses subgroups found fingolimod significantly increased risk lower respiratory infection rr 148 95 ci 119185 2 0 herpes virus infection rr 134 95 ci 101178 2 9 appears dosedependent increase risk infection associated fingolimod 05 mg rr 115 95 ci 107125 2 91 125 mg rr 111 95 ci 097128 2 81 pinteraction 066 conclusions compared placebo active treatments fingolimod associated 16 increase risk infection especially lower respiratory infection herpes virus infection risk infection associated fingolimod might dose relatedpmid33763062 pmcpmc7982402 doi103389 fimmu2021611711,0.0
cholesterol alters mitophagy impairing optineurin recruitment lysosomal clearance alzheimers disease background emerging evidence indicates impaired mitophagymediated clearance defective mitochondria critical event alzheimers disease ad pathogenesis amyloidbeta metabolism microtubuleassociated protein tau reported regulate key components mitophagy machinery however mechanisms lead mitophagy dysfunction ad fully deciphered previously shown intraneuronal cholesterol accumulation can disrupt autophagy flux resulting low clearance study examine impact neuronal cholesterol changes mitochondrial removal autophagymethodsregulation pink1parkinmediated mitophagy investigated conditions acute vitro chronic vivo high cholesterol loading using cholesterolenriched shsy5y cells cultured primary neurons transgenic mice overexpressing active srebf2 sterol regulatory element binding factor 2 mice increasing age express amyloid precursor protein familial alzheimer swedish mutation mo huapp695swe mutant presenilin 1 ps1de9 together active srebf2resultsin cholesterolenriched shsy5y cells cultured primary neurons high intracellular cholesterol levels stimulated mitochondrial pink1 accumulation mitophagosomes formation triggered impairing lysosomalmediated clearance antioxidant recovery cholesterolinduced mitochondrial glutathione gsh depletion prevented mitophagosomes formation indicating mitochondrial ros involvement interestingly brain cholesterol accumulated chronically aged apppsen1srebf2 mice mitophagy flux affected early steps pathway defective recruitment key autophagy receptor optineurin optn sustained cholesterolinduced alterations apppsen1srebf2 mice promoted agedependent accumulation optn hdac6positive aggresomes disappeared vivo treatment gsh ethyl ester gshee analyses postmortem brain tissues individuals ad confirmed findings showing optn aggresomelike structures correlated high mitochondrial cholesterol levels late ad stagesconclusionsour data demonstrate accumulation intracellular cholesterol reduces clearance defective mitochondria suggest recovery cholesterol homeostasis mitochondrial scavenging ros potential therapeutic targets ad,0.0
multiple sclerosis patient management covid19 pandemic practical recommendations portuguese multiple sclerosis study group geem front neurol 2021 mar 8 12613769 doi 103389 fneur2021613769 ecollection 2021abstractthe spread covid19 pandemic imposed significant challenges healthcare provision requiring changes conventional patient management particularly chronic diseases like multiple sclerosis ms increase patient safety reduce risk infection ensuring appropriate regular followup telemedicine gained prominence valid alternative facetoface appointments however urgency implementation lack experience ms centers led ad hoc extremely diverse approaches now merit standardized refined indeed teleconsultation fully replace facetoface visits certainly can will incorporated part routine care ms patients near future bearing mind portuguese multiple sclerosis study group geem developed set recommendations usage telemedicine management ms patients pandemic future consensus obtained twostep modified delphi methodology resulting 15 recommendations detailed manuscriptpmid33790847 pmcpmc8006454 doi103389 fneur2021613769,0.0
old weapon new function piwiinteracting rnas neurodegenerative diseases abstractpiwiinteracting rnas pirnas small noncoding transcripts highly conserved across species regulate gene expression pre posttranscriptional processes pirnas originally discovered germline cells protect transposable element expression promote maintain genome stability recent decade emerging roles pirnas revealed including roles sterility tumorigenesis metabolic homeostasis neurodevelopment neurodegenerative diseases review summarize pirna biogenesis c elegans drosophila mice elaborate upon pirnas mitigate harmful effects transposons lastly recent findings pirna participation neurological diseases highlighted speculate mechanisms pirna action development progression neurodegenerative diseases understanding roles pirnas neurological diseases may facilitate applications diagnostic therapeutic practice,0.0
effects transcranial direct current stimulation cognition mood pain fatigue multiple sclerosis systematic review metaanalysis front neurol 2021 mar 8 12626113 doi 103389 fneur2021626113 ecollection 2021abstractbackground study aimed evaluate effects transcranial direct current stimulation tdcs cognition mood disturbance pain fatigue people multiple sclerosis pwms methods literature search performed articles published january 1990 may 2020 pubmed medline web science using following keywords abbreviation combinations multiple sclerosis transcranial direct current stimulation mean effect size es 95 confidence interval calculated domain interest results seventeen articles total 383 pwms included analysis cognition strong effect size found trial administering symbol digit modalities test es 115 whereas trials applying attention network test showed negative effect size 049 moderate strong effect sizes observed mood disturbance mean es 092 pain mean es 059 fatigue mean es 060 subgroup analyses msrelated fatigue showed high low intensities stimulation lead nearly degree favorable effects pronounced effects observed studies administering fatigue severity scale compared studies using fatigue measures modified fatigue impact scale conclusion results provide preliminary evidence tdcs favorable effect cognitive processing speed mood disturbance pain fatigue ms however effects cognition fatigue vary based specific assessment usedpmid33763014 pmcpmc7982804 doi103389 fneur2021626113,0.0
multiple sclerosis intimacy sexuality questionnaire msisq15 translation adaptation validation polish version patients multiple sclerosis spinal cord injury background polish physicians researchers lack extensive precise instrument native language evaluating sexual dysfunction individuals neurogenic disorders aim study create culturally adapted validated polish language version multiple sclerosis intimacy sexuality questionnaire msisq15 persons multiple sclerosis ms spinal cord injury sci methodsinternational recommendations standardized methods instrument validation followed sexually active patients ms sci completed msisq15 international index erection function iief15 men pelvic organ prolapse urinary incontinence sexual questionnaire pisq31 women iief15 pisq31 used reference questionnaires responses collected baseline test 2 weeks retest resultswe recruited 299 polishspeaking patients ms sci interviews disclosed translated questionnaire optimal content validity crosscultural adaptation msisq15 scores correlated significantly severity sexual dysfunction evaluated iief15 r 0487 pisq31 r 0709 correlations substantiated high quality construct criterion validity analysis reliability presented good internal consistency cronbachs alpha 093 total score ms patients 086 total score sci patients reproducibility intraclass correlation coefficients 091 total score ms patients 092 total score sci patients ceiling floor effectsconclusionsthe polish version msisq15 exhibited excellent measurement properties suitable reliable instrument assess sexual dysfunction ms sci individuals polish msisq15 will enhance routine clinical practice assist research neurogenic patients poland,0.0
multiparametric quantitative mri neurological diseases front neurol 2021 mar 8 12640239 doi 103389 fneur2021640239 ecollection 2021abstractmagnetic resonance imaging mri gold standard imaging technique diagnosis monitoring many neurological diseases however application conventional mri clinical routine mainly limited visual detection macroscopic tissue pathology since mixed tissue contrasts depending hardware protocol parameters hamper application assessment subtle diffuse impairment structural tissue integrity multiparametric quantitative q mri determines tissue parameters quantitatively enabling detection microstructural processes related tissue remodeling aging neurological diseases contrast measuring tissue atrophy via structural imaging multiparametric qmri allows investigating biologically distinct microstructural processes precede changes tissue volume facilitates comprehensive characterization tissue alterations revealing early impairment microstructural integrity specific diseaserelated patterns far qmri techniques employed wide range neurological diseases including particular conditions inflammatory cerebrovascular neurodegenerative pathology numerous studies suggest qmri might add valuable information including detection microstructural tissue damage areas appearing normal conventional mri unveiling microstructural correlates clinical manifestations review will give overview current qmri techniques relevant tissue parameters potential applications neurological diseases early differential diagnosis monitoring disease progression evaluating effects therapeutic interventionspmid33763021 pmcpmc7982527 doi103389 fneur2021640239,0.0
pilot study impact exercise intervention brain structure cognition psychosocial symptoms individuals relapsingremitting multiple sclerosis background despite pharmacological treatment many individuals multiple sclerosis ms continue experience symptoms medication side effects exercise holds promise ms changes brain structure following exercise thoroughly investigated important cognitive psychosocial variables rarely primary outcomes aim pilot study investigate whether 12week exercise intervention improve white matter integrity brain cognition symptoms fatigue depressed mood individuals relapsingremitting ms rrms methodthirteen participants completed 12 weeks speeded walking baseline postintervention testing included 3t diffusion tensor imaging dti assess white matter neuropsychological testing assess cognition fatigue mood image preprocessing analyses performed functional magnetic resonance imaging brain software libraryresultspostintervention significant changes white matter compared baseline postintervention individuals rrms performed significantly better symbol digit modalities test sdmt reported fewer perceived memory problems endorsed less fatigue performance significantly different trails digit span significant changes reports moodconclusionalthough 12 weeks speeded walking improve white matter integrity exercise may hold promise managing symptoms rrms context study population,0.0
early effect intrathecal rituximab progressive multiple sclerosis effrite clinical trial mult scler int 2021 mar 8 20218813498 doi 101155 2021 8813498 ecollection 2021abstractbackground progressive phase multiple sclerosis ms characterized intrathecal compartmentalization inflammation involving bcells within meningeal follicles resisting available immunosuppressive treatments new therapeutic paradigm may target inflammation injecting immunosuppressive drugs inside central nervous system compartmentmethods designed singlecenter openlabel randomized controlled phase ii study designed evaluate safety efficacy rituximab progressive ms effrite trial clinicaltrial registration nct02545959 patients randomized three arms 1 1 1 control group rituximab 20 mg group intravenous+it iv+it group main outcome change levels csf biomarkers inflammation osteopontin secondary outcomes changes levels csf biomarkers axonal loss neurofilament light chain clinical mri changesresults ten patients included 2 4 4 adverse event occurred opn level remained stable csf time point whereas nfl slightly decreased 87 day 21 p 002 clinical parameters remained stable leptomeningeal enhancements remained unchangedconclusion clinical outcome biomarkers inflammation dramatically modified injection rituximab probably due limited efficiency csf drug issues future studies discussedpmid33763241 pmcpmc7964121 doi101155 2021 8813498,0.0
pexidartinib treatment alexander disease model mice reduces macrophage numbers increases glial fibrillary acidic protein levels yet minimal impact disease phenotypes background alexander disease axd rare neurodegenerative disorder caused dominant mutations gene encoding glial fibrillary acidic protein gfap intermediate filament primarily expressed astrocytes axd mutant gfap combination increased gfap expression result astrocyte dysfunction accumulation rosenthal fibers neuroinflammatory environment consisting primarily macrophage lineage cells observed axd patients mouse modelsmethodsto examine macrophage lineage cells serve therapeutic target axd gfap knockin mutant axd model mice treated colonystimulating factor 1 receptor csf1r inhibitor pexidartinib effects pexidartinib treatment disease phenotypes assessedresultsin axd model mice pexidartinib administration depleted macrophages cns caused elevation gfap transcript protein levels minimal impacts phenotypes including body weight stress response activation chemokine cytokine expression t cell infiltrationconclusionstogether results highlight complicated role macrophages can play neurological diseases support use pexidartinib therapy axd,0.0
homotaurine limits spreading t cell autoreactivity within cns ameliorates disease model multiple sclerosis sci rep 2021 mar 8 11 1 5402 doi 101038 s41598021847513abstractmost multiple sclerosis ms patients given currently available diseasemodifying drugs dmds experience progressive disability accordingly need new treatments can limit generation new waves t cell autoreactivity drive disease progression notably immune cells express gabaareceptors gabaars whose activation antiinflammatory effects gaba administration can ameliorate disease models type 1 diabetes rheumatoid arthritis covid19 show oral gaba cross bloodbrain barrier bbb affect course murine experimental autoimmune encephalomyelitis eae contrast oral administration bbbpermeable gabaarspecific agonist homotaurine ameliorates monophasic eae well advancedstage relapsingremitting eae rreae homotaurine treatment beginning first peak paralysis reduced spreading th17 th1 responses priming immunogen new myelin t cell epitope within cns antigenpresenting cells apc isolated homotaurinetreated mice displayed attenuated ability promote autoantigenspecific t cell proliferation ability homotaurine treatment limit epitope spreading within cns along safety record makes excellent candidate help treat ms inflammatory disorders cnspmid33686135 doi101038 s41598021847513,1.0
right ventricular myocardial deoxygenation patients pulmonary artery hypertension background pulmonary arterial hypertension pah progressive right ventricular rv dysfunction believed largely secondary rv ischaemia recent pilot study demonstrated feasibility oxygensensitive os cardiovascular magnetic resonance cmr detect invivo rv myocardial oxygenation aims present study therefore assess prevalence rv myocardial ischaemia relationship rv myocardial interstitial changes pah patients nonobstructive coronaries corelate functional haemodynamic parametersmethodswe prospectively recruited 42 patients right heart catheter rhc proven pah 11 healthy age matched controls cmr examination involved standard functional imaging oscmr imaging native t1 mapping oscmr signal intensity si index stress rest signal intensity acquired rv anterior rv freewall rv inferior segments t1 maps acquired using shortened modified looklocker inversion recovery shmolli inferior rv segmentresultsthe inferior rv oscmr si index significantly lower pah patients compared healthy controls 95 74428 vs 125 9246 p 002 inferior rv oscmr si significant correlation rv inferior wall thickness r 07 p 0001 rhc mean pulmonary artery pressure mpap r 04 p 002 compared healthy controls patients pah higher native t1 inferior rv wall 1303 11071612 vs 1232 11591288 ms p 0049 addition significant difference inferior rv t1 values idiopathic pah systemic sclerosis associated pah patients 1242 11071612 vs 1386 12191552 ms p 0007conclusionblunted oscmr si suggests presence invivo microvascular rv dysfunction pah patients native t1 inferior rv segments significantly increased pah patients particularly among systemic sclerosis associated pah group,0.0
reallife clinical practice studies multiple sclerosis farm hosp 2021 mar 8 45 2 5152 doi 107399 fh11663no abstractpmid33709885 doi107399 fh11663,0.0
correction development evaluation interactive webbased decisionmaking programme relapse management people multiple sclerosis power ms2 study protocol randomised controlled trial amendment paper published can accessed via original article,0.0
neuronoligodendrocyte interactions structure integrity axons front cell dev biol 2021 mar 8 9653101 doi 103389 fcell2021653101 ecollection 2021abstractthe myelination axons oligodendrocytes highly complex celltocell interaction oligodendrocytes axons reciprocal signaling relationship oligodendrocytes receive cues axons direct myelination oligodendrocytes subsequently shape axonal structure conduction oligodendrocytes necessary maturation excitatory domains axon including nodes ranvier help buffer potassium support neuronal energy metabolism disruption oligodendrocyteaxon unit traumatic injuries alzheimers disease demyelinating diseases multiple sclerosis results axonal dysfunction can culminate neurodegeneration review discuss mechanisms demyelination loss oligodendrocytes compromise axons highlight intraaxonal cascades initiated demyelination can result irreversible axonal damage restoration oligodendrocyte myelination neuroprotective therapies targeting intraaxonal cascades likely therapeutic potential disorders oligodendrocyte support axons disruptedpmid33763430 pmcpmc7982542 doi103389 fcell2021653101,1.0
thyroid hormone sexdependent role nervous system regulation disease abstractthyroid hormone th regulates many functions including metabolism cell differentiation nervous system development alteration thyroid hormone level body can lead nervous systemrelated problems linked cognition visual attention visual processing motor skills language memory skills th also associated neuropsychiatric disorders including schizophrenia bipolar disorder anxiety depression males females display sexspecific differences neuronal signaling steroid hormones including testosterone estrogen considered prime regulators programing neuronal signaling male femalespecific manner however steroid hormones th also one key signaling molecules regulate different brain signaling male femalespecific manner thyroidrelated diseases neurological diseases show sexspecific incidence however molecular mechanisms behind clear hence will beneficial understand th acts male female brains critical genes signaling networks review highlighted role th nervous system regulation disease outcome given special emphasis sexspecific role male female brains network model also presented provides critical information thregulated genes signaling disease,0.0
development novel sensitive translational immunoassay detect plasma glial fibrillary acidic protein gfap murine traumatic brain injury background glial fibrillary acidic protein gfap emerged promising fluid biomarker several neurological indications including traumatic brain injury tbi leading cause death disability worldwide humans serum plasma gfap levels can predict brain abnormalities including hemorrhage computed tomography ct scans magnetic resonance imaging mri however assays quantify plasma serum gfap preclinical models yet availablemethodswe developed validated novel sensitive gfap immunoassay assay mouse plasma meso scale discovery immunoassay platform validated assay performance robustness precision limits quantification dilutional linearity parallelism recovery stability selectivity preanalytical factors provide proofofconcept data assay translational research tool tbi alzheimers disease ad plasma gfap measured mice exposed tbi using closed head impact model engineered rotational acceleration chimera model app ps1 mice normal reduced levels plasma highdensity lipoprotein hdl resultswe performed partial validation novel assay found performance parameters studied similar assays used quantify human gfap clinical neurotrauma blood specimens assays used measure murine gfap tissues specifically demonstrated intraassay cv 50 interassay cv 72 lower limit detection llod 90 pg ml lower limit quantification lloq 248 pg ml upper limit quantification uloq least 16 5339 pg ml dilution linearity calibrators 20 200 000 pg ml 90123 recovery dilution linearity plasma specimens 32fold 96112 recovery spike recovery 67100 excellent analyte stability specimens exposed 7 freezethaw cycles 168 h 4 c 24 h room temperature rt 30 days 20 c also observed elevated plasma gfap mice 6 h tbi aged app ps1 mice plasma hdl deficiency assay also detects gfap serumconclusionsthis novel assay valuable translational tool may help provide insights mechanistic pathophysiology tbi ad,0.0
effect fecal microbiota transplantation neurological restoration spinal cord injury mouse model involvement braingut axis background spinal cord injury sci patients display disruption gut microbiome gut dysbiosis exacerbate neurological impairment sci models cumulative data support important role gut microbiome sci investigated hypothesis fecal microbiota transplantation fmt healthy uninjured mice sci mice may exert neuroprotective effectresultsfmt facilitated functional recovery promoted neuronal axonal regeneration improved animal weight gain metabolic profiling enhanced intestinal barrier integrity gi motility sci mice highthroughput sequencing revealed levels phylum firmicutes family christensenellaceae genus butyricimonas reduced fecal samples sci mice fmt remarkably reshaped gut microbiome also fmttreated sci mice showed increased amount fecal shortchain fatty acids scfas correlated alteration intestinal permeability locomotor recovery furthermore fmt downregulated il1 nfb signaling spinal cord nfb signaling gut following sciconclusionour study demonstrates reprogramming gut microbiota fmt improves locomotor gi functions sci mice possibly antiinflammatory functions scfas video abstract,1.0
probabilistic multiple sclerosis lesion detection using superpixels markov random fields multiple sclerosis ms common neurodegenerative disease among young adults diagnosis monitoring ms performed t2weighted t2 flair magnetic resonance imaging ms lesions appear hyperintense spots white matter recent years multiple algorithms proposed detect lesions varying success rates greatly depend amount priori information required algorithm use atlas involvement expert guide segmentation process work fully automatic method rely priori anatomical information proposed evaluated proposed algorithm based oversegmentation superpixels classification means gaussmarkov measure fields gmmf main advantage oversegmentation preserves borders tissues gmmf classifier robust noise computationally efficient proposed segmentation applied two stages first segment brain region detect hyperintense spots within brain proposed method evaluated synthetic images brainweb well real images ms patients proposed method produces competitive results respect algorithms state art without requiring user assistance anatomical prior information,0.0
altered oligodendrocytes spinal enlargements streptozotocin diabetic rats disturbances sensory motor nerve conduction velocity spinal cord well degenerated myelin sheaths observed diabetic patients animal models indeed oligodendrocytes ols important neuroglial cells generate myelin central nervous system spinal enlargement including cervical lumbar enlargements innervates limbs thus purposes study examine compare ultrastructural alterations ols spinal enlargements streptozotocin stz induced diabetic rats controls thirteen male spraguedawley rats induced stz citrate buffer six control rats injected buffer solution rats sacrificed inductions four shortterm dm twentyfour weeks longterm dm selected spinal enlargements processed transmission electron microscopy ol alterations cervical lumbar enlargements apparently shortterm dm nuclei ols became swelled chromatin clumping cytoplasmic organelles moderately damaged longterm dm ols contained shrinkage nuclei thick heterochromatin clumping severely degenerated mitochondria disrupted cristae broken membranes observed moreover distended fragmented rough endoplasmic reticulum observed large clear areas present cytoplasm additionally loosening splitting destruction myelin lamellae found study can provide important preliminary information alteration ols spinal cords diabetic patients might involve impairments sensory motor conduction velocities individuals,1.0
qualitative quantitative ultrastructural analysis mitochondria adrenal gland cortex action viperidae family snake venoms viperidae venoms composed mixture constituents enzymatic nonenzymatic actions act ultrastructural components cells tissues number mitochondria mitochondrial area number mitochondrial cristae adrenal glands cortex treated snake venoms tested 3 6 24 hours venom injections mitochondria quantitative changes showed statistically significant decrease number mitochondria past 3 6 24 h increase mitochondrial area 6 h crotalus vegrandis venom present significant differences crotalus pifanorum bothrops venezuelensis venoms 24 h escalation mitochondrial area tested venoms number mitochondrial cristae 3 h present important differences control treatment 6 h number mitochondrial cristae initiated decrease activities 3 venoms action 24 h observation qualitative observations possible witness intense damage mitochondria loss swelling membranes disappearance cristae appearance myelin figures started 3 h crotalus bothrops venoms injections damages probably due cytotoxic effects phospholipases metalloproteases proteolytic activities present viperidae snake venoms evident crotalus venoms far know results define novel finding suggest viperidae snake venoms extremely toxic mammalian mitochondria,1.0
modified method luxol fast blue paraffinembedded myelin sheath staining histological techniques study animal human tissues staining examining microscope demonstrate axonal degeneration demyelination histological studies luxol fast blue staining gold standard techniques study new histochemical method based modified luxol fast blue staining myelin sheath sciatic nerve tissues described sciatic nerves rats removed sciatic nerve immersed 10 formaldehyde one week embedded paraffin block next thin sections 5 m cut using microtome stained conventional modified luxol fast blue results showed new method modified luxol fast blue staining can accurately identify myelin sciatic nerve fibers current study showed luxol fast blue combination light green good effect myelin coloration results study comparable lfb combination sirius red,1.0
wholebody vibration training patients neurodegenerative disease cochrane review consumer summary select wholebody vibration training patients neurodegenerative disease cochrane review consumer summary sitja rabert m rigau comas d fort vanmeerhaeghe santoyo medina c roque ifm romerorodriguez d bonfill cosp x cochrane database systematic reviews 2012 issue 2 systematic review background wholebody vibration wbv may complementary training standard physical rehabilitation programmes appears potential benefits sensorimotor system performance patients neurodegenerative diseases objectives aim review examine efficacy wbv improve functional performance according basic activities daily living adl neurodegenerative diseases additionally wanted assess possible effect signs symptoms disease body balance gait muscle performance quality life adverse events search methods searched following electronic databases cochrane central register controlled trials central cochrane library 2011 issue 4 medline 1964 6 may 2011 via pubmed embase 1980 6 may 2011 via ovid pedro 1929 may 2011 via website cinahl september 2011 via ovid psycinfo 1806 6 may 2011 via ovid selection criteria included randomised controlled trials comparing single multiple sessions wbv passive intervention active physical therapy wbv different vibration parameters data collection analysis two review authors independently selected trials inclusion assessed trial quality extracted data disagreement resolved discussion necessary referred third review author main results included 10 trials six focused parkinsons disease four multiple sclerosis none studies reported data primary outcome functional performance parkinsons disease pooling two studies single session wbv caused significant improvement gait measured using timed go test tug comparison standing exercises mean difference 309 95 confidence interval 560 059 p 002 i2 0 nevertheless longer duration wbv show significant results comparison physical therapy body balance signs symptoms measured unified parkinsons disease rating scale updrs multiple sclerosis evidence shortterm longterm effect wbv body balance gait muscle performance quality life adverse events reported trials trials reported intervention appeared safe authors conclusions insufficient evidence effect wbv training functional performance neurodegenerative disease patients also insufficient evidence regarding beneficial effects signs symptoms disease body balance gait muscle strength quality life compared active physical therapy passive interventions parkinsons disease multiple sclerosis studies assessing functional tests accurately assessing safety needed definitive recommendation established full text sometimes free may available link s helpdoi pubmed pdf locatorpublisher,0.0
effectiveness vocational rehabilitation intervention return work employment persons multiple sclerosis cochrane review consumer summary select effectiveness vocational rehabilitation intervention return work employment persons multiple sclerosis cochrane review consumer summary khan f ng l turnerstokes l cochrane database systematic reviews 2009 issue 1 systematic review background multiple sclerosis neurological disease frequently affects adults working age resulting range physical cognitive psychosocial deficits impact workforce participation although literature supports vocational rehabilitation vr approaches persons multiple sclerosis pwms evidence effectiveness yet established objectives evaluate effectiveness vr programs compared alternative programs care usual return work workability employment pwms evaluate cost effectiveness programs search methods searched cochrane multiple sclerosis groups trials register february 2011 pedro 1990 2011 isi science citation index 1981 2011 cochrane rehabilitation related therapies field trials register national health service national research register selection criteria randomized controlled clinical trials including beforeafter controlled trials compare vr rehabilitation alternative intervention standard lesser form intervention wait list controls data collection analysis two reviewers selected trials rated methodological quality independently best evidence synthesis performed based methodological quality trials grouped terms type setting vr programs main results two trials one rct one cct total 80 participants met review criteria trials scored poorly methodological quality assessment insufficient evidence vr programs competitive employment altering rates job retention changes employment improvement rates reentry labour force b altering work ability improving participants confidence accommodation request process employability maturity job seeking activity evidence assimilated changes proportions persons supported employment disability pensions costeffectiveness authors conclusions inconclusive evidence support vr pwms however review highlights challenges providing vr pwms clinicians need aware vocational issues understand manage barriers maintaining employment proactive timely vr programs incorporate practical solutions deal work disability workplace accommodation educate employers wider community liaison policy makers imperative government initiatives encourage work focused vr programs future research vr focus improving methodological scientific rigour clinical trials development appropriate valid outcome measures cost effectiveness vr programs full text sometimes free may available link s helppubmed central doi pubmed pdf locatorpublisher,0.0
nursing management patient multiple sclerosisselect abstract available article,0.0
respiratory muscle training multiple sclerosis cochrane review consumer summary select respiratory muscle training multiple sclerosis cochrane review consumer summary rietberg mb veerbeek jm gosselink r kwakkel g van wegen eeh cochrane database systematic reviews 2017 issue 12 systematic review background multiple sclerosis ms chronic disease central nervous system affecting approximately 25 million people worldwide people ms may experience limitations muscular strength endurance including respiratory muscles affecting functional performance exercise capacity respiratory muscle weakness can also lead diminished performance coughing may result aspiration pneumonia even acute ventilatory failure complications frequently cause death ms training respiratory muscles might improve respiratory function cough efficacy objectives assess effects respiratory muscle training versus type training training respiratory muscle function pulmonary function clinical outcomes people ms search methods searched trials register cochrane multiple sclerosis rare diseases central nervous system group 3 february 2017 contains trials cochrane central register controlled trials central medline embase cinahl lilacs trial registry databases clinicaltrialsgov international clinical trials registry platform two authors independently screened records yielded search handsearched reference lists review articles primary studies checked trial registers protocols contacted experts field identify published unpublished trials selection criteria included randomized controlled trials rcts investigated efficacy respiratory muscle training versus control people ms data collection analysis one reviewer extracted study characteristics study data included rcts two reviewers independently crosschecked extracted data two review authors independently assessed risk bias cochrane risk bias assessment tool least two rcts provided data type outcome performed metaanalyses assessed certainty evidence according grade approach main results included six rcts comprising 195 participants ms two rcts investigated inspiratory muscle training threshold device three rcts expiratory muscle training threshold device one rct regular breathing exercises eighteen participants 10 dropped trials reported serious adverse events pooled analyzed data 5 trials n 137 inspiratory expiratory muscle training using fixedeffect model one outcome compared active control metaanalysis showed inspiratory muscle training resulted significant difference maximal inspiratory pressure mean difference md 650 cmh2o 95 confidence interval ci 739 2038 p 036 i2 0 maximal expiratory pressure md 822 cmh2o 95 ci 2620 977 p 037 i2 0 significant benefit predicted maximal inspiratory pressure md 2092 cmh2o 95 ci 603 3581 p 0006 i2 18 metaanalysis randomeffects model failed show significant difference predicted maximal expiratory pressure md 586 cmh2o 95 ci 1063 2235 p 049 i2 55 studies report outcomes healthrelated quality life three rcts compared expiratory muscle training versus active control sham training fixedeffect model metaanalysis failed show significant difference groups regard maximal expiratory pressure md 833 cmh2o 95 ci 093 1759 p 018 i2 42 maximal inspiratory pressure md 354 cmh2o 95 ci 504 1212 p 042 i2 41 one trial assessed quality life finding differences groups predetermined secondary outcomes forced expiratory volume forced vital capacity peak flow pooling possible however two trials inspiratory muscle training assessed fatigue using fatigue severity scale range scores 0 56 finding difference groups md 028 points 95 ci095 039 p 042 i2 0 due low number studies included perform cumulative metaanalysis subgroup analyses possible perform metaanalysis adverse events serious adverse mentioned included trials quality evidence low outcomes limitations design implementation well imprecision results authors conclusions review provides lowquality evidence resistive inspiratory muscle training resistive threshold device moderately effective postintervention improving predicted maximal inspiratory pressure people mild moderate ms whereas expiratory muscle training showed significant effects sustainability favourable effect inspiratory muscle training unclear impact observed effects quality life full text sometimes free may available link s helppubmed central doi pubmed pdf locatorpublisher,0.0
interventions preventing falls people multiple sclerosis cochrane review consumer summary select interventions preventing falls people multiple sclerosis cochrane review consumer summary hayes s galvin r kennedy c finlayson m mcguigan c walsh cd coote s cochrane database systematic reviews 2019 issue 11 systematic review background multiple sclerosis ms one prevalent diseases central nervous system recent prevalence estimates indicating ms directly affects 23 million people worldwide fall rates 56 reported among people ms recent metaanalysis clinical guidelines outline evidencebased approach falls interventions ms need synthesised information regarding effectiveness falls prevention interventions ms objectives aim review evaluate effectiveness interventions designed reduce falls people ms specific objectives included comparing 1 falls prevention interventions controls 2 different types falls prevention interventions search methods searched trials register cochrane multiple sclerosis rare diseases cns group cochrane central register controlled trials 2018 issue 9 medline pubmed 1966 12 september 2018 embase embasecom 1974 12 september 2018 cumulative index nursing allied health literature ebscohost 1981 12 september 2018 latin american caribbean health science information database bireme 1982 12 september 2018 clinicaltrialsgov world health organization international clinical trials registry platform psycinfo 1806 12 september 2018 physiotherapy evidence database 1999 12 september 2018 selection criteria selected randomised controlled trials quasirandomised trials interventions reduce falls people ms included trials examined falls prevention interventions compared controls different types falls prevention interventions primary outcomes included falls rate risk falling number falls per person adverse events data collection analysis two review authors screened studies selection assessed risk bias extracted data used rate ratio rar 95 confidence interval compare falls rate groups risk falling used risk ratio rr 95 ci based number fallers group main results total 839 people ms 12 177 individuals randomised 13 included trials mean age participants 52 years 36 62 years percentage women participants ranged 59 85 studies included people types ms trials compared exercise intervention intervention different types falls prevention interventions included two comparisons 1 falls prevention intervention versus control 2 falls prevention intervention versus another falls prevention intervention common interventions tested exercise single intervention education single intervention functional electrical stimulation exercise plus education risk bias included studies mixed nine studies demonstrating high risk bias related one aspects methodology evidence uncertain regarding effects exercise versus control falls rate rar 068 95 ci 043 106 lowquality evidence number fallers rr 085 95 ci 051 143 lowquality evidence adverse events rr 125 95 ci 026 603 lowquality evidence data available quality life outcomes comparing exercise control majority comparisons falls interventions controls demonstrated evidence effect favour either group primary outcomes comparison different falls prevention interventions heterogeneity intervention types across studies prohibited pooling data relation secondary outcomes evidence effect favour exercise interventions compared controls balance function smd 050 95 ci 009 092 selfreported mobility smd 1630 95 ci 934 2326 objective mobility smd 028 95 ci 007 050 secondary outcomes assessed grade criteria results must interpreted caution authors conclusions evidence regarding effects interventions preventing falls ms sparse uncertain evidence base demonstrates mixed risk bias low low certainty evidence evidence favour exercise interventions improvement balance function mobility however must interpreted caution secondary outcomes assessed grade criteria results represent data small number studies robust rcts examining effectiveness multifactorial falls interventions falls outcomes needed full text sometimes free may available link s helppubmed central doi pubmed pdf locatorpublisher,0.0
effectiveness physical therapy interventions reducing fear falling among individuals neurological diseases systematic review metaanalysisselect effectiveness physical therapy interventions reducing fear falling among individuals neurological diseases systematic review metaanalysis abou l alluri fliflet du y rice la archives physical medicine rehabilitation 2021 jan 102 1 132154 systematic review objective summarize effectiveness physical therapy pt interventions reduce fear falling fof among individuals living neurological diseases data sources pubmed pedro scopus web science psycinfo cinahl sportdiscus searched inception december 2019 study selection clinical trials either primary secondary aim reduce fof among adults neurological diseases selected data extraction potential papers screened eligibility data extracted two independent researchers risk bias assessed cochrane risk bias tool randomized clinical trials nih quality assessment tool prepost studies metaanalysis performed among trials presenting similar clinical characteristics grading recommendations assessment development evaluation grade used rate overall quality evidence results sixtyone trials 3 954 participants included review 53 trials 3 524 participants metaanalysis included studies presented general low high risk bias combination gait balance training found significantly effective compared gait training alone reducing fof among individuals parkinsons disease pd mean difference md 1180 95 ci 822 1538 p 0001 homebased exercise leisure exercise demonstrated significant improvement reducing fof usual care multiple sclerosis ms md 1527 95 ci 615 2438 p 0001 statistically significant betweengroups differences reported among individuals stroke spinal cord injury sci overall quality evidence presented review ranges low moderate according assessment grade approach conclusion gait lower limb training combined balance training effective reducing fof individuals pd also homebased leisure exercise effective among individuals ms however due several limitations included studies research needed examine effectiveness fof intervention among individuals neurological diseases full text sometimes free may available link s helpdoi pubmed pdf locatorpublisher,0.0
non pharmacological interventions spasticity multiple sclerosis cochrane review consumer summary select non pharmacological interventions spasticity multiple sclerosis cochrane review consumer summary amatya b khan f la mantia l demetrios m wade dt cochrane database systematic reviews 2013 issue 2 systematic review background spasticity commonly experienced people multiple sclerosis ms contributes overall disability population wide range non pharmacological interventions used isolation pharmacological agents treat spasticity ms evidence effectiveness yet determined objectives assess effectiveness various non pharmacological interventions treatment spasticity adults ms search methods literature search performed using specialised register cochrane multiple sclerosis rare diseases central nervous system review group using cochrane ms group trials register among sources contains central medline embase cinahl lilacs pedro june 2012 manual searching relevant journals screening reference lists identified studies reviews carried abstracts published proceedings conferences also scrutinised selection criteria randomised controlled trials rcts reported non pharmacological intervention s treatment spasticity adults ms compared form control intervention sham placebo interventions lower level different types intervention minimal intervention waiting list controls treatment interventions given different settings included data collection analysis three review authors independently selected studies extracted data assessed methodological quality studies using grades recommendation assessment development evaluation grade tool bestevidence synthesis metaanalysis possible due methodological clinical statistical heterogeneity included studies main results nine rcts n 341 participants 301 included analyses investigated various types intensities non pharmacological interventions treating spasticity adults ms interventions included physical activity programmes physiotherapy structured exercise programme sports climbing transcranial magnetic stimulation intermittent theta burst stimulation itbs repetitive transcranial magnetic stimulation rtms electromagnetic therapy pulsed electromagnetic therapy magnetic pulsing device transcutaneous electrical nerve stimulation tens whole body vibration wbv studies scored low methodological quality assessment implying high risk bias low level evidence physical activity programmes used isolation combination interventions pharmacological non pharmacological repetitive magnetic stimulation itbs rtms without adjuvant exercise therapy improving spasticity adults ms evidence benefit exists support use tens sports climbing vibration therapy treating spasticity population authors conclusions low level evidence non pharmacological interventions physical activities given conjunction interventions magnetic stimulation electromagnetic therapies beneficial effects spasticity outcomes people ms wide range non pharmacological interventions used treatment spasticity ms robust trials needed build evidence interventions full text sometimes free may available link s helpdoi pubmed pdf locatorpublisher,0.0
identification management depression multiple sclerosisselect identification management depression multiple sclerosis nntntnttms depression working group toward optimized practice ntntntt2015ntntnttpractice guidelinentntnttnttntttobjective alberta clinicians skills tools assess diagnose treat manage depression patients multiple sclerosis ms within primary care target population adults 18 years age older exclusions children less 18 years agefull text may available publisherntttntttttttadditional document s available guideline quick reference guide,0.0
treatment ataxia multiple sclerosis cochrane review consumer summary select treatment ataxia multiple sclerosis cochrane review consumer summary mills rj yap l young ca cochrane database systematic reviews 2007 issue 1 systematic review background disabling tremor ataxia common multiple sclerosis ms 80 patients experience tremor ataxia point disease variety treatments available ranging pharmacotherapy stereotactic neurosurgery neurorehabilitation objectives assess efficacy tolerability pharmacological nonpharmacologic treatments ataxia patients ms search strategy following electronic resources searched cochrane ms group trials register june 2006 cochrane central register controlled trials central issue 2 2006 national health service national research register nrr including medical research council clinical trials directory issue 2 2006 medline january 1996 june 2006 embase jan 1988 june 2006 manual searches bibliographies relevant articles pertinent medical neurology journals abstract books major neurology ms conferences 2001 2006 also performed direct communication experts drug companies sought selection criteria blinded randomised trials either placebocontrolled compared two treatments included trials testing pharmacological agents must participant assessor blinding trials testing surgical interventions effects physiotherapy participants blinded treatment must independent assessors blinded treatment crossover trials included data collection analysis three independent reviewers extracted data findings trials summarised metaanalysis performed due inadequacy outcome measures methodological problems studies reviewed main results ten randomised controlled trials met inclusion criteria six placebocontrolled studies pharmacotherapy four comparative studies one stereotactic neurosurgery three neurorehabilitation reviewed standardised outcome measures used across studies general pharmacotherapies unrewarding data neurosurgery rehabilitation insufficient lead change practice authors conclusions absolute comparative efficacy tolerability pharmacotherapies treat ataxia ms poorly documented recommendations can made guide prescribing although studies neurosurgery neurorehabilitation showed promising results absolute indications treating methods developed standardised well validated measures ataxia tremor need developed employed larger randomised controlled trials careful blinding full text sometimes free may available link s helpdoi pubmed pdf locatorpublisher,0.0
rehabilitation people multiple sclerosis overview cochrane reviews cochrane review consumer summary select background multiple sclerosis ms major cause chronic neurological disability significant longterm disability burden often requiring comprehensive rehabilitation objectives systematically evaluate evidence published cochrane reviews clinical trials summarise evidence regarding effectiveness safety rehabilitation interventions people ms pwms improve patient outcomes highlight current gaps knowledge methods searched cochrane database systematic reviews december 2017 identify cochrane reviews assessed effectiveness organised rehabilitation interventions pwms two reviewers independently assessed quality included reviews using revised assessment multiple systematic reviews ramstar tool quality evidence reported outcomes using grade framework main results overall included 15 reviews published cochrane library comprising 164 randomised controlled trials rcts four controlled clinical trials total 10 396 participants included reviews evaluated wide range rehabilitation interventions including physical activity exercise therapy hyperbaric oxygen therapy hbot wholebody vibration occupational therapy cognitive psychological interventions nutritional dietary supplements vocational rehabilitation information provision telerehabilitation interventions management spasticity assessed reviews high moderate methodological quality based ramstar criteria moderatequality evidence suggested physical therapeutic modalities exercise physical activities improved functional outcomes mobility muscular strength reduced impairment fatigue improved participation quality life moderatequality evidence suggested inpatient outpatient multidisciplinary rehabilitation programmes led longerterm gains levels activity participation interventions provided information improved patient knowledge lowquality evidence suggested neuropsychological interventions symptommanagement programmes spasticity whole body vibration telerehabilitation improved patient outcomes evidence rehabilitation modalities inconclusive due lack robust studies authors conclusions evidence suggests regular specialist evaluation followup assess needs patients types ms appropriate rehabilitation interventions may benefit although certainty evidence varies across different types interventions evaluated reviews structured multidisciplinary rehabilitation programmes physical therapy exercise physical activities can improve functional outcomes mobility muscle strength aerobic capacity quality life overall evidence many rehabilitation interventions interpreted cautiously majority included reviews include data current studies studies appropriate design report type intensity modalities costeffectiveness needed address current gaps knowledge,0.0
efns guideline treatment multiple sclerosis relapses report efns task force treatment multiple sclerosis relapsesselect efns guideline treatment multiple sclerosis relapses report efns task force treatment multiple sclerosis relapses nntntnttsellebjerg f barnes d filippini g midgard r montalban x rieckmann p selmaj k visser lh sorensen ps european federation neurological societies ntntntteuropean journal neurology 2005 dec 12 12 939946ntntnttpractice guidelinentntnttnttntttcopyright release abstract grantedabstract full text sometimes free may available link s helpdoi pubmed publisher,0.0
exercise therapy multiple sclerosis cochrane review consumer summary select exercise therapy multiple sclerosis cochrane review consumer summary rietberg mb brooks d uitdehaag bmj kwakkel g cochrane database systematic reviews 2004 issue 3 systematic review background intervention proven effective modifying longterm disease prognosis multiple sclerosis ms exercise therapy considered important part symptomatic supportive treatment patients objectives assess effectiveness exercise therapy patients ms terms activities daily living healthrelated quality life search strategy searched cochrane ms group specialised register searched march 2004 cochrane central register controlled trials central cochrane library issue 2 2004 medline 1966 march 2004 embase 1988 march 2004 cinahl 1982 march 2004 pedro 1999 march 2004 manual search journal multiple sclerosis screening reference lists identified studies reviews also searched abstracts published proceedings conferences selection criteria randomised controlled trials rcts reported exercise therapy adults ms presently experiencing exacerbation outcomes include measures activity limitation healthrelated quality life data collection analysis two reviewers independently extracted data methodological quality included trials disagreements resolved discussion results analysed using bestevidence synthesis based methodological quality main results nine highmethodologicalquality rcts 260 participants met inclusion criteria six trials focussed comparison exercise therapy versus exercise therapy whereas three trials compared two interventions met definition exercise therapy best evidence synthesis showed strong evidence favour exercise therapy compared exercise therapy terms muscle power function exercise tolerance functions mobilityrelated activities moderate evidence found improving mood evidence observed exercise therapy fatigue perception handicap compared exercise therapy finally evidence found specific exercise therapy programmes successful improving activities participation exercise treatments evidence deleterious effects exercise therapy described included studies authors conclusions results present review suggest exercise therapy can beneficial patients ms experiencing exacerbation urgent need consensus core set outcome measures used exercise trials addition studies experimentally control dose treatment type ms include sufficient contrast experimental control groups full text sometimes free may available link s helppubmed central doi pubmed pdf locatorpublisher,0.0
palliative care interventions people multiple sclerosis cochrane review consumer summary select background people multiple sclerosis ms complex symptoms different types needs demands include manage burden physical disability well organise daily life restructure social roles family work preserve personal identity community roles keep selfsufficiency personal care part integrated care network palliative care teams trained keep open full competent lines communication symptoms disease progression advanced care planning endoflife issues wishes teams create treatment plan total management symptoms supporting people families decisionmaking despite advances research existence many interventions reduce disease activity slow progression ms condition remains lifelimiting disease symptoms impact negatively lives people families objectives assess effects benefits harms palliative care interventions compared usual care people form multiple sclerosis relapsingremitting ms rrms secondaryprogressive ms spms primaryprogressive ms ppms progressiverelapsing ms prms also aimed compare effects different palliative care interventions search methods 31 october 2018 conducted literature search specialised register cochrane ms rare diseases central nervous system review group contains trials central medline embase cinahl lilacs clinicaltrialsgov world health organization international clinical trials registry platform also searched psycinfo pedro opengrey also handsearched relevant journals screened reference lists published reviews contacted researchers palliative care multiple sclerosis selection criteria randomised controlled trials rcts cluster randomised trials eligible inclusion well first phase crossover trials included studies compared palliative care interventions versus usual care also included studies compared palliative care interventions versus another type palliative interventions data collection analysis used standard cochrane methodological procedures summarised key results certainty evidence summary finding table reported outcomes six months postintervention main results three studies 146 participants met selection criteria two studies compared multidisciplinary fasttrack palliative care versus multidisciplinary standard care waitinglist control one study compared multidisciplinary palliative approach versus multidisciplinary standard care different time points 12 16 24 weeks two rcts parallel design total 94 participants one crossover design 52 participants three studies assessed palliative care homebased intervention one three studies included participants neurodegenerative diseases ms people subset randomised population assessed risk bias included studies using cochranes risk bias tool found evidence differences intervention control groups longtime followup six months postintervention following outcomes mean change healthrelated quality life seiqol higher scores mean better quality life md 480 95 ci 1232 2192 participants 62 studies 1 lowcertainty evidence serious adverse events rr 097 95 ci 044 212 participants 76 studies 1 22 events lowcertainty evidence hospital admission rr 078 95 ci 024 252 participants 76 studies 1 10 events lowcertainty evidence three included studies assess following outcomes long term followup six months post intervention fatigue anxiety depression disability cognitive function relapsefree survival sustained progressionfree survival find trial compared different types palliative care authors conclusions based findings rcts included review uncertain whether palliative care interventions beneficial people ms low lowcertainty evidence regarding difference palliative care interventions versus usual care longterm healthrelated quality life adverse events hospital admission patients ms intermediateterm followup also uncertain effects palliative care outcomes healthrelated quality life measured different assessments seiqol msis disability anxiety depression,0.0
multidisciplinary rehabilitation adults multiple sclerosis cochrane review consumer summary select multidisciplinary rehabilitation adults multiple sclerosis cochrane review consumer summary khan f turnerstokes l ng l kilpatrick t amatya b cochrane database systematic reviews 2007 issue 2 systematic review background multidisciplinary md rehabilitation important component symptomatic supportive treatment multiple sclerosis ms evidence base effectiveness yet established objectives assess effectiveness organized md rehabilitation adults ms explore rehabilitation approaches effective different settings outcomes affected search methods searched cochrane multiple sclerosis groups trials register 25 february 2011 pedro 1990 2011 cochrane rehabilitation related therapies field trials register national health service national research register nrr relevant journals handsearched language restrictions applied selection criteria randomized controlled trials rct controlled clinical trials cct compared md rehabilitation routinely available local services lower levels intervention trials comparing interventions different settings different levels intensity data collection analysis three reviewers selected trials rated theirmethodological quality independently best evidence synthesis based onmethodological quality performed trials grouped terms setting type rehabilitation duration patient follow main results ten trials 9 rcts 1 cct 954 participants 73 caregivers met inclusion criteria eight rcts scored well one rct one cct scored poorly methodological quality assessment despite change level impairment strong evidence support inpatient md rehabilitation producing shortterm gains levels activity disability participation patients ms moderate evidence support inpatient outpatient rehabilitation programmes compared control waitlist groups improving disability bladder related activity participation outcomes 12 months following md rehabilitation intervention outpatient homebased rehabilitation programmes limited evidence shortterm improvements symptoms disability high intensity programmes translated improvement participation quality life low intensity programmes conducted longer period strong evidence longerterm gains quality life also limited evidence benefits carers although studies reported potential costsavings convincing evidence regarding longterm costeffectiveness programmes possible suggest best dose therapy supremacy one therapy another review highlights limitations rcts rehabilitation settings need better designed randomized multiple centre trials authors conclusions md rehabilitation programmes change level impairment can improve experience people ms terms activity participation regular evaluation assessment persons rehabilitation recommended research appropriate outcome measures optimal intensity frequency cost effectiveness rehabilitation therapy longer time period needed future research rehabilitation focus improving methodological scientific rigour clinical trials full text sometimes free may available link s helpdoi pubmed pdf locatorpublisher,0.0
telerehabilitation persons multiple sclerosis cochrane review consumer summary select telerehabilitation persons multiple sclerosis cochrane review consumer summary khan f amatya b kesselring j galea m cochrane database systematic reviews 2015 issue 4 systematic review background telerehabilitation emerging method extends rehabilitative care beyond hospital facilitates multifaceted often psychotherapeutic approaches modern management patients using telecommunication technology home community although wide range telerehabilitation interventions trialed persons multiple sclerosis pwms evidence effectiveness unclear objectives investigate effectiveness safety telerehabilitation intervention pwms improved patient outcomes specifically review addresses following questions telerehabilitation achieve better outcomes compared traditional facetoface intervention types telerehabilitation interventions effective setting influence specific outcomes impairment activity limitation participation search methods performed literature search using cochrane multiple sclerosis rare diseases central nervous system review group specialised register 9 july 2014 handsearched relevant journals screened reference lists identified studies contacted authors additional data selection criteria randomised controlled trials rcts controlled clinical trials ccts reported telerehabilitation intervention s pwms compared form control intervention lower level different types intervention minimal intervention waitinglist controls treatment usual care interventions given different settings adults ms data collection analysis two review authors independently selected studies extracted data three review authors assessed methodological quality studies using gradepro software gradepro 2008 bestevidence synthesis metaanalysis possible due marked methodological clinical statistical heterogeneity included trials measurement tools used hence performed bestevidence synthesis using qualitative analysis main results nine rcts one two reports n 531 participants 469 included analyses investigated variety telerehabilitation interventions adults ms mean age participants varied 41 52 years mean 465 years mean years since diagnosis 77 190 years mean 123 years majority participants women proportion ranging 56 87 mean 74 relapsingremitting course ms interventions complex one rehabilitation component included physical activity educational behavioural symptom management programmes studies scored low methodological quality assessment overall review found lowlevel evidence telerehabilitation interventions reducing shortterm disability symptoms fatigue also lowlevel evidence supporting telerehabilitation longer term improved functional activities impairments fatigue pain insomnia participation measured quality life psychological outcomes limited data process evaluation participants therapists satisfaction data available cost effectiveness adverse events reported result telerehabilitation interventions authors conclusions currently limited evidence efficacy telerehabilitation improving functional activities fatigue quality life adults ms range telerehabilitation interventions might alternative method delivering services ms populations insufficient evidence support types telerehabilitation interventions effective setting robust trials needed build evidence clinical cost effectiveness interventions full text sometimes free may available link s helppubmed central doi pubmed pdf locatorpublisher,0.0
occupational therapy multiple sclerosis cochrane review consumer summary select occupational therapy multiple sclerosis cochrane review consumer summary steultjens emj dekker j bouter lm cardol m van de nes jcm van den ende chm cochrane database systematic reviews 2003 issue 3 systematic review background multiple sclerosis ms patients referred occupational therapy complaints fatigue limb weakness alteration upper extremity fine motor coordination loss sensation spasticity causes limitations performance activities daily living social participation primary purpose occupational therapy enable individuals participate selfcare work leisure activities want need perform objectives determine whether occupational therapy interventions ms patients improve outcome functional ability social participation health related quality life search strategy searched cochrane ms group trials register january 2003 cochane central register controlled trials cochrane library issue 4 2002 medline january 2003 embase december 2002 cinahl december 2002 amed december 2002 scisearch december 2002 reference lists articles selection criteria controlled randomized nonrandomized controlled studies addressing occupational therapy ms patients eligible inclusion data collection analysis two reviewers independently assessed methodological quality included trials disagreements resolved discussion list proposed van tulder 1997 used assess methodological quality outcome measures calculated standardized mean differences analysed results using bestevidence synthesis based type design methodological quality significant findings outcome process measures main results one randomized clinical trial identified two included studies controlled clinical trial study prepost test design three studies involved 271 people total two studies evaluated energyconservation course groups patients one study evaluated counseling intervention results energy conservation studies biased designs used poor methodological quality small number included patients high quality rct counseling reported nonsignificant results authors conclusions basis review conclusions can stated whether occupational therapy improves outcomes ms patients lack randomized controlled efficacy studies intervention categories occupational therapy demonstrates urgent need future research occupational therapy multiple sclerosis initially survey occupational therapy practice ms patients including characteristics needs patients necessary develop research agenda efficacy studies full text sometimes free may available link s helpdoi pubmed pdf locatorpublisher,0.0
behavioural exercise interventions targeting fatigue show promise multiple sclerosis systematic review narrative synthesis metaanalysis consumer summary select behavioural exercise interventions targeting fatigue show promise multiple sclerosis systematic review narrative synthesis metaanalysis consumer summary nntntnttmossmorris r harrison safari r norton s van der linden ml picariello f thomas s white c mercer tntntnttbehaviour research therapy 2021 feb 137103464ntntnttsystematic reviewntntnttnttntttfatigue common highly debilitating symptom multiple sclerosis ms metaanalytic systematic review detailed narrative synthesis examined randomisedcontrolled rcts controlled trials behavioural exercise interventions targeting fatigue adults ms assess treatments offer promise reducing fatigue severity impact medline embase psycinfo electronic databases amongst others searched august 2018 thirtyfour trials 12 exercise 16 behavioural 6 combined n 2 434 participants met inclusion criteria data 31 studies n 1 991 participants contributed metaanalysis risk bias using cochrane tool study quality grade assessed pooled smd endoftreatment effects selfreported fatigue exercise interventions n 13 084 95 ci 120 047 behavioural interventions n 16 037 95 ci 053 022 combined interventions n 5 016 95 ci 036 004 heterogeneity high overall study quality low exercise interventions moderate behavioural combined interventions considering health care professional time subgroup results suggest webbased cognitive behavioural therapy fatigue balance multicomponent exercise interventions may costefficient therapies need testing large rcts longterm followup help define implementable fatigue management pathway ms permission excerpta medica incfull text sometimes free may available link s helpdoi pubmed publisher,0.0
exercise therapy fatigue multiple sclerosis cochrane review consumer summary select exercise therapy fatigue multiple sclerosis cochrane review consumer summary heine m van de port rietberg mb van wegen eeh kwakkel g cochrane database systematic reviews 2015 issue 9 systematic review background multiple sclerosis ms immunemediated disease central nervous system affecting estimated 13 million people worldwide characterised variety disabling symptoms excessive fatigue frequent fatigue often reported invalidating symptom people ms various mechanisms directly indirectly related disease physical inactivity proposed contribute degree fatigue exercise therapy can induce physiological psychological changes may counter mechanisms reduce fatigue ms objectives determine effectiveness safety exercise therapy compared noexercise control condition another intervention fatigue measured selfreported questionnaires people ms search methods searched cochrane multiple sclerosis rare diseases central nervous system group trials specialised register among sources contains trials cochrane central register controlled trials central 2014 issue 10 medline 1966 october 2014 embase 1974 october 2014 cinahl 1981 october 2014 lilacs 1982 october 2014 pedro 1999 october 2014 clinical trials registries october 2014 two review authors independently screened reference lists identified trials related reviews selection criteria included randomized controlled trials rcts evaluating efficacy exercise therapy compared exercise therapy interventions adults ms included subjective fatigue outcome trials fatigue measured using questionnaires primarily assessed fatigue subscales questionnaires measured fatigue subscales questionnaires primarily designed assessment fatigue explicitly used data collection analysis two review authors independently selected articles extracted data determined methodological quality included trials methodological quality determined means cochrane risk bias tool pedro scale combined body evidence summarised using grade approach results aggregated using metaanalysis trials provided sufficient data main results fortyfive trials studying 69 exercise interventions eligible review including 2 250 people ms prescribed exercise interventions categorised endurance training 23 interventions muscle power training nine interventions taskoriented training five interventions mixed training 15 interventions eg yoga 17 interventions thirtysix included trials 1 603 participants provided sufficient data outcome fatigue metaanalysis general exercise interventions studied mostly participants relapsingremitting ms phenotype expanded disability status scale less 60 based 26 trials used nonexercise control found significant effect fatigue favour exercise therapy standardized mean difference smd 053 95 confidence interval ci 073 033 p value 001 however significant heterogeneity trials i2 58 mean methodological quality well combined body evidence moderate considering different types exercise therapy found significant effect fatigue favour exercise therapy compared exercise endurance training smd fixed effect 043 95 ci 069 017 p value 001 mixed training smd random effect 073 95 ci 123 023 p value 001 training smd fixed effect 054 95 ci 079 029 p value 001 across studies one fall reported given number ms relapses reported exercise condition n 25 nonexercise control condition n 26 exercise seem associated significant risk ms relapse however general ms relapses defined reported poorly authors conclusions exercise therapy can prescribed people ms without harm exercise therapy particularly endurance mixed training may reduce self reported fatigue however still important methodological issues overcome unfortunately trials explicitly include people experienced fatigue target therapy fatigue specifically use validated measure fatigue primary measurement outcome full text sometimes free may available link s helpdoi pubmed pdf locatorpublisher,0.0
multiple sclerosis management multiple sclerosis primary secondary care full guideline cg186 select multiple sclerosis management multiple sclerosis primary secondary care full guideline cg186 nntntnttbarker n bostock p brex p chataway j cooper p de gromoboy hendrie w hodgson hourihan s kernick d rowe e warner r royal college physicians national institute health care excellence ntntntt2014ntntnttpractice guidelinentntnttnttntttthis record abstractfull text may available publisherntttntttttttadditional document s available guideline appendix appendices f nappendix appendices h m nappendix appendix g,0.0
nonpharmacological interventions chronic pain multiple sclerosis cochrane review consumer summary select nonpharmacological interventions chronic pain multiple sclerosis cochrane review consumer summary amatya b young j khan f cochrane database systematic reviews 2018 issue 12 systematic review background chronic pain common significantly impacts lives persons multiple sclerosis pwms various types nonpharmacological interventions widely used hospital ambulatory mobility settings improve pain control pwms effectiveness safety many nonpharmacological modalities still unknown objectives review aimed investigate effectiveness safety nonpharmacological therapies management chronic pain pwms specific questions addressed review include following 1 nonpharmacological interventions unidisciplinary multidisciplinary rehabilitation effective reducing chronic pain pwms 2 type nonpharmacological interventions unidisciplinary multidisciplinary rehabilitation effective least effective setting reducing chronic pain pwms search methods literature search performed using specialised register cochrane ms rare diseases central nervous system review group using cochrane ms group trials register contains central medline embase cinahl lilacus clinicaltrialsgov world health organization international clinical trials registry platform 10 december 2017 handsearching relevant journals screening reference lists relevant studies carried selection criteria published randomised controlled trials rcts crossover studies compared nonpharmacological therapies control intervention managing chronic pain pwms included clinical controlled trials ccts eligible inclusion data collection analysis three review authors independently selected studies extracted data assessed methodological quality studies using grades recommendation assessment development evaluation grade tool bestevidence synthesis pooling data metaanalysis possible due methodological clinical statistically heterogeneity included studies main results overall 10 rcts 565 participants investigated different nonpharmacological interventions management chronic pain ms fulfilled review inclusion criteria nonpharmacological interventions evaluated included transcutaneous electrical nerve stimulation tens psychotherapy telephone selfmanagement hypnosis electroencephalogram eeg biofeedback transcranial random noise stimulation trns transcranial direct stimulation tdcs hydrotherapy ai chi reflexology lowlevel evidence use nonpharmacological interventions chronic pain tens ai chi tdcs trns telephonedelivered selfmanagement program eeg biofeedback reflexology pain intensity pwms although improved changes pain scores secondary outcomes fatigue psychological symptoms spasm interventions limited methodological biases within studies authors conclusions despite use wide range nonpharmacological interventions treatment chronic pain pwms evidence interventions still limited insufficient studies robust methodology greater numbers participants needed justify effect interventions management chronic pain pwms full text sometimes free may available link s helppubmed central doi pubmed pdf locatorpublisher,0.0
18ffdg positron emission tomography scanning systemic sclerosisassociated interstitial lung disease pilot study background interstitial lung disease common complication systemic sclerosis sscild remains difficult accurately predict course progressing ild metabolically active suggesting 18ffdg tracer tool managing sscildmethodsin center ssc patients controls nonhodgkin lymphoma cured firstline regimen received pet ct screened retrospectively fdg uptake visual intensity pattern suvmax systematically recorded 30 regions interest rois linked ssc blind reviewing 2 independent nuclear medicine physicians using standardized formresultsamong 545 ssc patients followed center 36 including 22 sscilds pet ct whose indication cancer screening cases mean sd age 579 130 years 20 36 females fourteen patients disease duration less 2 years third anticentromere antibodies 278 antitopoisomerase antibodies pulmonary fdg uptakes higher ssc patients controls n 89 especially ild compared without ild pulmonary fdg uptakes positively correlated ild severity fibrosis extent fvc dlco significant difference found fdg uptakes extrathoracic rois progressing sscilds within 2 years pet ct n 9 significant higher pulmonary fdg uptakes baseline stable sscilds n 13 conclusionpet ct useful tool assessment severity prediction pulmonary function outcome sscild,0.0
teriflunomide treatment associated optic nerve recovery early multiple sclerosis ther adv neurol disord 2021 mar 6 141756286421997372 doi 101177 1756286421997372 ecollection 2021abstractbackground aims various attempts made support recovery following optic neuritis respective trials mostly negative aim study determine whether diseasemodifying treatment dmt following first manifestation relapsingremitting multiple sclerosis influences longterm outcomesmethods total 79 patients identified evaluated relapse dmt induction 12 months following treatment induction either glatiramer acetate glat interferonbeta ifn teriflunomide trf lowcontrast letter acuity lcla fullfield visualevoked potentials ffvep compared treatment groups using multivariable regression models impact trf treatment induction compared ifn glat following relapses outside optic nerves evaluated independent cohort 122 patients magnetic resonance imaging mri outcomes rates confirmed improvement relapserelated disability evaluatedresults trftreated patients exhibited higher lcla lower relative p100 latencies normalized felloweye findings significant following covariateadjustment multivariable analyses cranial mri lesion load well disability progression rates significantly different groups cohort patients following relapses showed differences confirmed improvement disabilityconclusion trf treatment associated favorable outcomes regarding functional optic nerve recovery following early multiple sclerosispmid33747129 pmcpmc7940774 doi101177 1756286421997372,0.0
zygomatic implant penetration central portion orbit case report background zygomatic implants proposed literature atrophic maxillary fixed oral rehabilitations aim present research evaluate clinical tomography assessment surgical complication zygomatic implant penetration orbitcase presentationa 56 yearold female patient visited pain swelling left orbit zygomatic implant protocol orbit invasion zygomatic implant screw confirmed cbct scan patient treated surgical implant removal peri postoperative symptoms assessed neurological complications reported followup ocular motility visual acuity well maintained purulent secretion inflammatory evidence reported postoperative healing phasesconclusionthe penetration orbit zygomatic implant positioning surgical complication compromise sight movements eye present case report zygomatic implant removal resulted uneventful healing phase recovery eye functions,0.0
blockage nlrp3 inflammasome activation ameliorates acute inflammatory injury longterm cognitive impairment induced necrotizing enterocolitis mice background necrotizing enterocolitis nec inflammatory gastrointestinal disease premature neonates high mortality morbidity underlining mechanism intestinal injury profound neurological dysfunction remains unclear aimed investigate involvement nlpr3 inflammasome activation necrelated enterocolitis neuroinflammation especially longterm cognitive impairment meanwhile explore protective effect nlrp3 inhibitor mcc950 nec micemethodsnlrp3 inflammasome activation intestine brain assessed nec mouse model nlrp3 inhibitor mcc950 administrated development nec survival rate histopathological injury intestine brain expression mature il1 proinflammatory cytokines analyzed longterm cognitive impairment evaluated behavioral testresultsthe expression nlrp3 mature il1 intestine brain greatly upregulated nec mice compared controls mcc950 treatment efficiently improved nec survival rate reduced intestinal brain inflammation ameliorated severity pathological damage organs additionally vivo blockage nlrp3 inflammasome mcc950 early life nec pups potently protected necassociated longterm cognitive impairmentconclusionsour findings suggest nlrp3 inflammasome activation participates necinduced intestinal brain injury early intervention nlrp3 inhibitor may provide beneficial therapeutic effect nec infants,0.0
human neural stem cellderived extracellular vesicles mitigate hallmarks alzheimers disease background regenerative therapies mitigate alzheimers disease ad neuropathology shown limited success recent era extracellular vesicles evs derived multipotent pluripotent stem cells shown considerable promise treatment dementia many neurodegenerative conditionsmethodsusing 5xfad accelerated transgenic mouse model ad now show regenerative potential human neural stem cell hnsc derived evs neurocognitive neuropathologic hallmarks ad brain two 6monthold 5xfad mice received single two intravenous retroorbital vein ro injections hnscderived evs respectivelyresultsro treatment using hnscderived evs restored fear extinction memory consolidation reduced anxietyrelated behaviors 46 weeks postinjection ev treatment also significantly reduced dense core amyloidbeta plaque accumulation microglial activation age groups results correlated partial restoration homeostatic levels circulating proinflammatory cytokines ad mice importantly ev treatment protected synaptic loss ad brain paralleled improved cognition mirna analysis ev cargo revealed promising candidates targeting neuroinflammation synaptic functionconclusionscollectively data demonstrate neuroprotective effects systemic administration stem cellderived evs remediation behavioral molecular ad neuropathologies,1.0
increased withinnetwork functional connectivity may predict neda status fingolimodtreated ms patients front neurol 2021 mar 5 12632917 doi 103389 fneur2021632917 ecollection 2021abstractonly studies evaluated brain functional changes associated diseasemodifying therapies dmts multiple sclerosis ms though none used composite measure clinical mri outcomes evaluate dmtrelated brain functional connectivity fc measures predictive shortterm outcome therefore investigated following 1 baseline fc differences patients showed evidence disease activity specific dmt 2 dmtrelated effects fc 3 possible relationships dmtrelated fc changes changes performance used previously analyzed dataset 30 relapsing ms patients underwent fingolimod treatment 6 months applied evidence disease activity neda3 status clinical response indicator treatment efficacy restingstate fmri data analyzed obtain within betweennetwork fc measures therapy 14 patients achieved neda3 status hereinafter neda 16 eda two groups significantly differed baseline neda group higher withinnetwork fc anterior posterior default mode auditory orbitofrontal right frontoparietal networks eda therapy neda showed significantly reduced withinnetwork fc posterior default mode left frontoparietal networks increased betweennetwork fc posterior default mode orbitofrontal networks also showed pasat improvement correlated greater withinnetwork fc decrease posterior default mode network greater betweennetwork fc increase significant longitudinal fc changes found eda taken together findings suggest neda status fingolimod related higher withinnetwork fc baseline consistent functional reorganization therapypmid33746887 pmcpmc7973271 doi103389 fneur2021632917,0.0
clinical utility cerebrospinal fluid vitamin dbinding protein novel biomarker diagnosis viral bacterial cns infections background rapid accurate diagnosis central nervous system cns infections important laboratory tests help diagnose cns infections even patient symptoms laboratory tests often reveal specific findings potential vitamin dbinding protein vdbp used biomarker viral bacterial cns infections studiedmethodsa total 302 subjects suspected cns infection underwent lumbar puncture included clinical laboratory data collected retrospectively vdbp levels measured cerebrospinal fluid csf samples genotyping gc gene encoding vdbp also performed vdbp levels analyzed compared cns infection pathogen csf opening pressure gc genotyperesultsa cns infection group n 90 noncns infection group n 212 studied terms receiver operating characteristic csf vdbp showed area curve 0726 diagnosis cns infection csf vdbp levels significantly different cns infection noninfection groups cns infection group enterovirus showed statistically lower distribution csf vdbp levels virus groups group csf opening pressure 25 cmh2o showed higher csf vdbp levels groups significant difference gc gene allele distribution cns infection noninfection groupsconclusionscsf vdbp levels increased patients cns infection csf vdbp showed potential new biomarker viral bacterial cns infections,0.0
seqqscorer automated quality control nextgeneration sequencing data using machine learning abstractcontrolling quality nextgeneration sequencing ngs data files necessary complex task address problem statistically characterize common ngs quality features develop novel quality control procedure involving treebased deep learning classification algorithms predictive models validated internal external functional genomics datasets extent generalizable data unseen species derived statistical guidelines predictive models represent valuable resource users ngs data better understand quality issues perform automatic quality control guidelines software available https githubcom salbrec seqqscorer,0.0
cognitive fatigue multiple sclerosis associated alterations functional connectivity monoamine circuits brain commun 2021 mar 5 3 2 fcab023 doi 101093 braincomms fcab023 ecollection 2021abstractfatigue highly prevalent debilitating symptom multiple sclerosis currently available treatment options limited efficacy development innovative efficacious targeted treatments fatigue multiple sclerosis marred limited knowledge underlying mechanisms one hypotheses postulates multiple sclerosis pathology might cause reduced monoaminergic release central nervous system consequences motivation mood attention applied recently developed receptorenriched analysis functional connectivity targets method investigate whether patients high low fatigue differ functional connectivity fc monoamine circuits brain recruited 55 patients multiple sclerosis classified highly fatigued mildly fatigued based scores cognitive subscale modified fatigue impact scale acquired restingstate functional mri scans derived individual maps connectivity associated distribution dopamine noradrenaline serotonin transporters measured positron emission tomography found patients high fatigue present decreased noradrenaline transporter nat enriched connectivity several frontal prefrontal areas compared lower fatigue natenriched fc predicted negatively individual cognitive fatigue scores findings support idea alterations catecholaminergic functional circuits underlie fatigue multiple sclerosis identify nat putative therapeutic target directed pathophysiologypmid33842886 pmcpmc8023545 doi101093 braincomms fcab023,0.0
preimplantation exogenous progesterone pregnancy sheep polyamines nutrient transport progestamedins background administration exogenous progesterone p4 ewes preimplantation period advances conceptus development implantation study determined effects exogenous p4 transport select nutrients pathways enhance conceptus development pregnant ewes n 38 treated either 25 mg p4 1 ml corn oil p4 n 18 1 ml corn oil alone co n 20 day 15 day 8 pregnancy hysterectomized either day 9 day 12 pregnancy endometrial expression genes encoding enzymes synthesis polyamines transporters glucose arginine glycine well progestamedins determined rtqpcrresultson day 12 pregnancy conceptuses p4treated ewes elongated cotreated ewes spherical mrna expression azin2 arginine decarboxylase lower endometria p4treated cotreated ewes day 9 pregnancy expression fgf10 progestamedin greater endometria co p4treated ewes day 12 gestation addition p4treated ewes necropsied day 9 gestation treatment p4 downregulated endometrial expression amino acid transporter slc1a4 day 12 pregnancyconclusionsresults indicated administration exogenous p4 preimplantation period advanced expression fgf10 may accelerate proliferation trophectoderm cells also correlated decreased expression glycine serine transporters polyamine synthesis enzyme azin2 research increased sample sizes may determine differential expression affects endometrial functions potentially embryonic loss,0.0
gait features influence amount intensity physical activity people multiple sclerosis medicine baltimore 2021 mar 5 100 9 e24931 doi 101097 md0000000000024931abstractalthough mutual relationship ambulation physical activity pa people multiple sclerosis pwms described several studies still lack detailed information way specific aspects gait cycle associated amount intensity pa study aimed verify existence possible relationships among pa parameters spatiotemporal parameters gait instrumentally assessedthirtyone pwms 17f 14 m mean age 525 mean expanded disability status scale edss score 31 requested wear triaxial accelerometer 24 hours day 7 consecutive days underwent instrumental gait analysis performed using inertial sensor located low back immediately pa assessment period main spatiotemporal parameters gait ie gait speed stride length cadence duration stance swing double support phase extracted processing trunk accelerations pa quantified using average number daily steps percentage time spent different pa intensity latter calculated using cutpoint sets previously validated ms existence possible relationships pa gait parameters assessed using spearman rank correlation coefficient rhogait speed stride length parameters highest number significant correlations pa features particular found moderately largely correlated number daily steps rho 062 p 001 percentage sedentary activity rho 044 p 001 percentage moderatetovigorous activity rho 048 p 001 small moderate significant correlations observed pa intensity duration stance swing double support phasesthe data obtained suggest relevant determinants associated higher intense levels pa freeliving conditions gait speed stride length simultaneous quantitative assessment gait parameters pa levels might represent useful support physical therapists tailoring optimized rehabilitative training interventionspmid33655958 doi101097 md0000000000024931,0.0
renal transplantation outcomes obese patients french cohortbased study background whilst number publications comparing relationship body mass index bmi kidney transplant recipients graft patient survival study assessed french patient cohortmethodsin study causespecific cox models used study patient graft survival several timetoevent measures logistic regressions performed study surgical complications 30 days posttransplantation well delayed graft functionresultsamong 4691 included patients 747 patients considered obese bmi level greater 30 kg m2 observed higher mortality obese recipients hr 137 p 00086 higher risks serious bacterial infections hr 124 p 00006 cardiac complications hr 145 p 00001 observed trend towards death censored graft survival hr 122 p 00666 significant increased risk early surgical complicationsconclusionswe showed obesity increased risk death serious bacterial infections cardiac complications obese french kidney transplant recipients epidemiologic studies aiming compare obese recipients versus obese candidates remaining dialysis needed improve guidelines obese patient transplant allocation,0.0
il27 il27r axis altered cd4 + cd8 + t lymphocytes multiple sclerosis patients clin transl immunology 2021 mar 5 10 3 e1262 doi 101002 cti21262 ecollection 2021abstractobjectives pro antiinflammatory properties attributed interleukin27 il27 nevertheless impact cytokine chronic inflammatory diseases multiple sclerosis ms remains illdefined investigated biology il27 specific receptor il27r ms patientsmethods levels il27 natural antagonist il27r measured elisa biological fluids cd4+ cd8+ t lymphocytes isolated untreated relapsingremitting ms patients healthy donors transcriptomewide analysis compared tcell subsets stimulated il27 expression il27r key immune factors stat phosphorylation cytokine production assessed flow cytometryresults observed elevated levels il27 serum cerebrospinal fluid ms patients compared controls moreover show specific il27mediated effects t lymphocytes reduced ms patients including induction pdl1 il27triggered stat3 signalling pathway enhanced cd4+ cd8+ t lymphocytes ms patients elevated il27r levels serum ms patients sufficient impair capacity il27 act immune cells demonstrate shedding il27r activated cd4+ t lymphocytes ms patients contributes increased il27r peripheral levels consequently can dampen il27 responsivenessconclusion work identifies several mechanisms altered il27 il27r axis ms patients especially t lymphocytes results underline importance characterising biology cytokines human patients prior design new therapeuticspmid33728050 pmcpmc7934284 doi101002 cti21262,0.0
associations serum shortchain fatty acids circulating immune cells serum biomarkers patients multiple sclerosis sci rep 2021 mar 4 11 1 5244 doi 101038 s41598021848818abstractaltered composition gut bacteria changes production bioactive metabolites shortchain fatty acids scfas implicated development multiple sclerosis ms however immunomodulatory actions scfas intermediaries ability influence ms pathogenesis uncertain study levels serum scfas correlated immune cell abundance phenotype well relevant serum factors blood samples taken first presentation clinically isolated syndrome cis early form ms ms compared healthy controls small significant reduction propionate levels serum patients cis ms compared healthy controls frequencies circulating t follicular regulatory cells t follicular helper cells significantly positively correlated serum levels propionate levels butyrate associated positively frequencies il10producing bcells negatively frequencies classswitched memory bcells tnf production polyclonallyactivated bcells correlated negatively acetate levels levels serum scfas associated changes circulating immune cells biomarkers implicated development mspmid33664396 doi101038 s41598021848818,0.0
openlabel pilot study veliparib lapatinib patients metastatic triplenegative breast cancer background poly adpribose polymerase inhibitors parpi approved cancer patients germline brca1 2 gbrca1 2 mutations efforts expand utility parpi beyond brca1 2 ongoing preclinical models triplenegative breast cancer tnbc intact dna repair previously shown induced synthetic lethality combined egfr inhibition parpi report safety clinical activity lapatinib veliparib patients metastatic tnbcmethodsa firstinhuman pilot study lapatinib veliparib conducted metastatic tnbc nct02158507 primary endpoint safety tolerability secondary endpoints objective response rates pharmacokinetic evaluation gene expression analysis pretreatment tumor biopsies performed key eligibility included tnbc patients measurable disease prior anthracyclinebased taxane chemotherapy patients gbrca1 2 mutations excludedresultstwenty patients enrolled 17 evaluable response median number prior therapies metastatic setting 1 range 02 fifty percent patients caucasian 45 africanamerican 5 hispanic evaluable patients 4 demonstrated partial response 2 stable disease doselimiting toxicities aes limited grade 1 2 drugdrug interactions noted exploratory gene expression analysis suggested baseline dna repair pathway score lower baseline immunogenicity higher responders compared nonrespondersconclusionslapatinib plus veliparib therapy manageable safety profile promising antitumor activity advanced tnbc investigation dual therapy egfr inhibition parp inhibition neededtrial registrationclinicaltrialsgov nct02158507 registered 12 september 2014,0.0
altered network properties c9orf72 repeat expansion cortical neurons due synaptic dysfunction background physiological disturbances cortical network excitability plasticity established widespread amyotrophic lateral sclerosis als frontotemporal dementia ftd patients including harbouring c9orf72 repeat expansion c9orf72re mutation common genetic impairment causal als ftd noting perturbations cortical function evidenced presymptomatically cortex associated widespread pathology cortical dysfunction thought early driver neurodegenerative disease progression however understanding altered network function manifests cellular molecular level clearmethodsto address generated cortical neurons patientderived ipscs harbouring c9orf72re mutations well isogenic expansioncorrected controls established model network activity neurons using multielectrode array electrophysiology mechanistically examined physiological processes underpinning network dysfunction using combination patchclamp electrophysiology immunocytochemistry pharmacology transcriptomic profilingresultswe find c9orf72re causes elevated network burst activity associated enhanced synaptic input yet lower burst duration attributable impaired presynaptic vesicle dynamics also show c9orf72re associated impaired synaptic plasticity moreover rnaseq analysis revealed dysregulated molecular pathways impacting synaptic function molecular cellular network deficits rescued crispr cas9 correction c9orf72re study provides mechanistic view early dysregulated processes underpin cortical network dysfunction alsftdconclusionthese findings suggest synaptic pathophysiology widespread alsftd early fundamental role driving altered network function thought contribute neurodegenerative processes patients overall importance identification previously unidentified defects pre postsynaptic compartments affecting synaptic plasticity synaptic vesicle stores network propagation directly impact upon cortical function,0.0
raff4 magnetization transfer diffusion tensor mri lysophosphatidylcholine induced demyelination remyelination rats front neurosci 2021 mar 4 15625167 doi 103389 fnins2021625167 ecollection 2021abstractremyelination naturally occurring response demyelination central role pathophysiology multiple sclerosis traumatic brain injury recently demonstrated novel mri technique entitled relaxation along fictitious field raff rotating frame rank n raffn achieved exceptional sensitivity detecting demyelination processes induced lysophosphatidylcholine lpc rat brain present work aim test whether raff4 along magnetization transfer mt diffusion tensor imaging dti capable detecting changes myelin content microstructure caused modifications myelin sheets around axons gliosis remyelination phase lpcinduced demyelination corpus callosum rats collected mri data raff4 mt dti 3 days injection demyelination stage 38 days injection remyelination stage lpc n 12 vehicle n 9 cell density myelin content assessed histology mri metrics detected differences lpcinjected control groups animals demyelination stage day 3 remyelination phase day 38 raff4 mt parameters fractional anisotropy axial diffusivity detected signs partial recovery consistent remyelination evident histology radial diffusivity undergone increase day 3 38 mean diffusivity revealed complete recovery correlating histological assessment cell density attributed gliosis combination raff4 mt dti potential differentiate normal demyelinated remyelinated axons gliosis thus may able provide detailed assessment white matter pathologies several neurological diseasespmid33746698 pmcpmc7969884 doi103389 fnins2021625167,1.0
standard care versus newwave corticosteroids treatment duchenne muscular dystrophy can better background pharmacological corticosteroid therapy standard care duchenne muscular dystrophy dmd aims control symptoms slow disease progression potent antiinflammatory action however major concern significant adverse effects associated long termusemainthis review discusses pros cons standard care treatment dmd compares novel data generated newwave dissociative corticosteroid vamorolone current status experimental antiinflammatory pharmaceuticals also reviewed insights regarding alternative drugs provide therapeutic advantageconclusionsalthough novel dissociative steroids may superior substitutes corticosteroids potential therapeutics explored repurposing developing novel pharmacological therapies capable addressing many pathogenic features dmd addition antiinflammation elicit greater therapeutic advantages,0.0
eye movement desensitization emd reduce posttraumatic stress disorderrelated stress reactivity indonesia ptsd patients study protocol randomized controlled trial background posttraumatic stress disorder ptsd may develop exposure traumatic event eye movement desensitization reprocessing emdr evidencebased psychological treatment ptsd yet unclear whether eye movements also reduce stress reactivity ptsd patients study aims test whether eye movements provided eye movement desensitization emd effective reducing stress reactivity ptsd patients compared retrievalonly control conditionmethodsthe study includes participants meet criteria ptsd public psychological services jakarta bandung indonesia one hundred ten participants randomly assigned either 1 eye movement desensitization group n 55 2 retrievalonly control group n 55 participants assessed baseline t0 posttreatment t1 1 month t2 3 months followup t3 participants exposed scriptdriven imagery procedure t0 t1 primary outcome heart rate variability hrv stress reactivity scriptdriven imagery secondary outcomes include heart rate hr preejection period pep saliva cortisol levels ptsd symptoms neurocognitive functioning symptoms anxiety depression perceived stress level quality lifediscussionif emd intervention effective reducing stress reactivity outcomes give us insight underlying mechanisms emdrs effectiveness ptsd symptom reductiontrial registrationisrctn registry isrctn55239132 registered 19 december 2017,0.0
predictive metagenomic analysis autoimmune disease identifies robust autoimmunity disease specific microbial signatures front microbiol 2021 mar 4 12621310 doi 103389 fmicb2021621310 ecollection 2021abstractwithin last decade numerous studies demonstrated changes gut microbiome associated specific autoimmune diseases due differences study design data quality control analysis statistical methods many results studies inconsistent incomparable better understand relationship intestinal microbiome autoimmunity completed comprehensive reanalysis 42 studies focusing gut microbiome 12 autoimmune diseases identify microbial signature predictive multiple sclerosis ms inflammatory bowel disease ibd rheumatoid arthritis ra general autoimmune disease using 16s rrna sequencing data shotgun metagenomics data used four machine learning algorithms random forest extreme gradient boosting xgboost ridge regression support vector machine radial kernel recursive feature elimination rank disease predictive taxa comparing disease vs healthy participants pairwise comparisons disease comparing performance models found two treebased methods xgboost random forest capable handling sparse multidimensional data consistently produce best results modeling identified number taxa consistently identified dysregulated general autoimmune disease model including odoribacter lachnospiraceae clostridium mogibacteriaceae implicating potential factors connecting gut microbiome autoimmune response computed pairwise comparison models identify disease specific taxa signatures highlighting role peptostreptococcaceae ruminococcaceae gemmiger ibd akkermansia butyricicoccus mogibacteriaceae ms connected subset taxa potential metabolic alterations based metagenomic metabolomic correlation analysis identifying 215 metabolites associated autoimmunitypredictive taxapmid33746917 pmcpmc7969817 doi103389 fmicb2021621310,0.0
safety efficacy lowdose intravenous arsenic trioxide systemic lupus erythematosus openlabel phase iia trial lupsenic background lupus animal model shown arsenic trioxide ato treatment acute promyelocytic leukaemia effective sle first clinical study determine safety efficacy short course intravenous ato patients active slemethodsthis phase iia openlabel doseescalating study enrolled 11 adult sle patients nonorgan threatening disease clinically active despite conventional therapy patients received 10 iv infusions ato within 24 days first group received 010 mg kg per injection doseescalating 015 mg kg second group 020 mg kg third group primary endpoint occurrence adverse events aes secondary endpoints number sle responder index 4 sri4 responders week 24 reduction corticosteroid dosage exploratory analysis collected longterm data safety attainment lupus low disease activity state lldas resultsfour serious aes occurred grade 3 neutropenia osteitis neuropathy 2 attributable ato neutropenia 2 patients treated mycophenolate two patients suffered severe flare last 4 weeks trial w24 five patients among 10 sri4 responders overall mean corticosteroid dosage decreased 1125 mg day baseline 6 mg day w24 p 001 long term 6 patients attained lldas w52 continued last followup median lldas duration 3 years range 24 conclusionsa short course ato acceptable safety profile sle patients encouraging efficacytrial registrationclinicaltrialsgov nct01738360 registered 30 november 2012,0.0
descriptive analysis realworld data fingolimod longterm treatment young adult rrms patients front neurol 2021 mar 3 12637107 doi 103389 fneur2021637107 ecollection 2021abstractbackground fingolimod gilenya approved adult pediatric patients highly active relapsingremitting multiple sclerosis rrms objectives objective describe effectiveness fingolimod young adults compared older patients clinical practice methods pangaea largest prospective multicenter noninterventional longterm study evaluating fingolimod rrms descriptively analyzed demographics ms characteristics severity two subgroups young adults 20 20 30 years older patients 30 years results young adults lower expanded disability status scale edss scores compared older patients 18 23 vs 32 baseline mean edss scores remained stable 5 years subgroups young adults higher annual relapse rates 20 17 vs 14 study entry reduced approximately 80 subgroups 5 years proportion patients clinical disease activity year 4 526 734 vs 669 patients 20 20 30 years 30 years respectively symbol digit modalities test score increased 1525 83 83 113 mean sd baseline patients 20 30 30 years conclusions realworld evidence suggests longterm treatment benefit fingolimod young rrms patientspmid33763018 pmcpmc7982917 doi103389 fneur2021637107,0.0
pien tze huang pzh multifunction medicinal agent traditional chinese medicine tcm review cellular molecular physiological mechanisms abstractrelevancepien tze huang pzh wellknown traditional chinese medicine tcm characterized multitude pharmacological effects hepatoprotection inhibition inflammation cell proliferative conditions many effects validated cellular molecular physiological levels date findings comprehensively disclosedobjectivesthis review aims provide critical summary recent studies focusing pzh multiple pharmacological effects result discuss novel perspectives related pzhs mechanisms action holistic view therapeutic activitiesmethodsa systematic review performed focusing pzh studies originated original scientific resources scientific literature retrieved work obtained international repositories including ncbi pubmed web science science direct china national knowledge infrastructure cnki databasesresultsthe major active componentes potential functions including hepatoprotective neuroprotective effects well anticancer antiinflammatory activities summarized categorized accordingly indicated pharmacological effects validated vitro vivo identification complex bioactive components pzh may provide basis therapeutic initiativesconclusionhere collectively discussed recent evidences covering pharmacological effects driven pzh review provides novel perspectives understanding modes action holistic view tcm rational development future clinical trials will certainly provide evidencebased medical evidences will also confirm therapeutic advantages pzh based current information available,1.0
effects vitamin d3 supplementation tgf il17 serum levels migraineurs post hoc analysis randomized clinical trial background although exact mechanism involved migraine pathogenesis remained uncertain different researches developed address role neuroinflammation immune dysfunction therefore considering immune protective functions vitamin d3 aimed investigate effects daily administration 2000 iu d3 supplements serum status immune markers migraine patientsmethods materialseighty episodic migraineurs randomly assigned two equal groups receive either vitamin d3 2000 iu d placebo 12week enrolled placebocontrolled doubleblind trial included serum concentrations transforming growth factorbeta tgf interleukin il 17 evaluated baseline trial via elisa methodresultsapplying ancova adjusted baseline levels confounding variables found serum level tgf significantly higher vitamin d group adjusted mean166550 ng l placebo group 136190 ng l experiment pvalue 0012 hand vitamin d prevented increment il17 serum level intervention group trial adjusted mean3784 ng l comparing controls adjusted mean7009 ng l pvalue 0039 pearson correlation analysis revealed significant positive correlation changes serum 25hydroxyvitamin d 25 oh d tgf r 0306 pvalue 0008 contrast significant correlations noted serum 25 oh d il17 changes throughout studyconclusionbased results study revealed 12week vitamin d3 supplementation 2000 iu day enhance th17 treg related cytokines balance episodic migraineurs although findings promising needed extendedtrial registrationthe trial registered iranian registry clinical trials irct 11 july 2018 irct code irct20151128025267n6 https wwwirctir trial 31246,0.0
two classes t1 hypointense lesions multiple sclerosis different clinical relevance front neurol 2021 mar 3 12619135 doi 103389 fneur2021619135 ecollection 2021abstractbackground hypointense lesions t1weighted images important clinical relevance multiple sclerosis patients traditionally spinecho se sequences used assess lesions termed black holes fast spoiled gradientecho fspgr sequences provide excellent alternative objective determine whether contrast difference t1 hypointense lesions surrounding normal white matter similar two sequences whether different lesion types identified whether clinical relevance lesions types different methods seventynine multiple sclerosis patients lesions manually segmented registered t1 sequences median intensity values lesions identified sequences kmeans clustering applied assess whether distinct clusters lesions can defined based intensity values se fspgr flair sequences standardized intensity lesions cluster compared intensity normal appearing white matter order see lesions stand white matter given sequence results 100 lesions fspgr images 69 se sequence cluster #1 exceeded standardized lesion distance z 23 p 005 cluster #2 787 lesions fspgr 177 lesions se sequence cutoff value meaning lesions easily seen se images lesion count second cluster lesions less identifiable se significantly correlated expanded disability status scale edss r 030 p 0006 disease duration r 033 p 0002 conclusion showed black holes can separated two distinct clusters based intensity values various sequences one related clinical parameters emphasizes joint role fspgr se sequences monitoring ms patients provides insight role black holes mspmid33746876 pmcpmc7966518 doi103389 fneur2021619135,0.0
knockdown circ_slc39a8 protects progression osteoarthritis regulating mir591 irak3 axis background dysregulation circular rnas circrnas identified various human diseases including osteoarthritis oa purpose study identify role mechanism circ_slc39a8 regulating progression oamethodsthe expression levels circ_slc39a8 mir591 potential target gene interleukin1receptorassociated kinase 3 irak3 identified quantitative realtime polymerase chain reaction qrtpcr cell viability apoptosis determined cell counting kit8 cck8 assay flow cytometry respectively relationship mir591 circ_slc39a8 irak3 predicted bioinformatics tools verified dualluciferase reporterresultscirc_slc39a8 irak3 upregulated mir591 downregulated oa cartilage tissues knockdown circ_slc39a8 inhibited apoptosis inflammation oa chondrocytes effects reversed downregulating mir591 promotion cell viability effects mir591 partially reversed irak3 overexpressionconclusionour findings indicated knockdown circ_slc39a8 delayed progression oa via modulating mir591irak3 axis providing new insight molecular mechanisms oa pathogenesis,0.0
correction signatures cell stress altered bioenergetics skin fibroblasts patients multiple sclerosis aging albany ny 2021 mar 3 online ahead printno abstractpmid33657013,0.0
development webbased mindfulness program people multiple sclerosis qualitative codesign study j med internet res 2021 mar 2 23 3 e19309 doi 102196 19309abstractbackground mindfulnessbased stress reduction efficacious treatment people chronic health problems however highly intensive timeconsuming barrier service provisionobjective study aims develop internetdelivered adapted version mindfulnessbased stress reduction people multiple sclerosis make intervention accessiblemethods codesigned webbased mindfulness program end users people multiple sclerosis n19 iterative feedback also collected subsample initial group end users n11 program reviewed experts n8 results identified three main themes common people multiple sclerosis dealing uncertainty fears future grief loss social isolation themes incorporated narratives throughout program people multiple sclerosis reviewed program gave feedback program relatable feasible acceptable experts agreed program appropriately represented main tenets mindfulness iterative feedback used refine programconclusions webbased mindfulness program developed viewed positively experts end users program reflects common concerns people multiple sclerosis potential meet important unmet psychological needs randomized controlled trial planned determine efficacy programpmid33650980 doi102196 19309,0.0
association csf proteins tau amyloid levels asymptomatic 70yearolds background increased knowledge evolution molecular changes neurodegenerative disorders alzheimers disease ad important understanding disease pathophysiology also crucial able identify validate disease biomarkers several biological changes occur early disease development already recognized need characterization pathophysiological mechanisms behind ad still remainsmethodsin study investigated cerebrospinal fluid csf levels 104 proteins 307 asymptomatic 70yearolds h70 gothenburg birth cohort studies using multiplexed antibody beadbased technologyresultsthe protein levels first correlated core ad csf biomarker concentrations total tau phosphotau amyloid beta a42 individuals sixtythree proteins showed significant correlations either total tau phosphotau a42 thereafter individuals divided based csf a42 a40 ratio clinical dementia rating cdr score determine early changes pathology cognition effect correlations compared associations analysed proteins csf markers groups found 33 proteins displaying significantly different associations amyloidpositive individuals amyloidnegative individuals defined csf a42 a40 ratio differences associations seen individuals divided cdr scoreconclusionswe identified series transmembrane proteins proteins associated anchored plasma membrane proteins involved connected synaptic vesicle transport associated csf biomarkers amyloid tau pathology ad studies needed explore proteins role ad pathophysiology,0.0
anticd20 disrupts meningeal bcell aggregates model secondary progressive multiple sclerosis neurol neuroimmunol neuroinflamm 2021 mar 2 8 3 e975 doi 101212 nxi0000000000000975 print 2021 mayabstractobjective therapies targeting b cells used clinic multiple sclerosis ms patients relapsing ms anticd20 therapy often suppresses relapse activity yet effect disease progression disappointing anticd20 therapeutic antibodies type within unique microenvironment brain type ii antibodies may beneficial type ii antibodies exhibit reduced complementdependent cytotoxicity increased capacity induce direct cell death independent host immune responsemethods compared effect type type ii anticd20 therapy new rodent model secondary progressive ms spms recapitulates principal histopathologic features ms including meningeal bcell aggregates focal mslike lesions induced injecting heatkilled mycobacterium tuberculosis piriform cortex mogimmunized mice groups mice treated anticd20 antibodies type rituxumab 10 mg kg type ii ga101 10 mg kg 4 weeks lesion initiation outcomes evaluated immunohistochemistryresults anticd20 therapy decreased extent glial activation significantly decreased number b t lymphocytes lesion resulted disruption meningeal aggregates moreover given dose type ii anticd20 therapy efficacious type also protected neuronal deathconclusions results indicate anticd20 may effective therapy spms bcell aggregates elimination cd20+ b cells alone sufficient cause disruption aggregates brainpmid33653962 doi101212 nxi0000000000000975,0.0
autologous hematopoietic stem cell transplantation ahsct evolving treatment avenue multiple sclerosis biologics 2021 mar 2 155359 doi 102147 btts267277 ecollection 2021abstractautologous hematopoietic stem cell transplantation ahsct considered novel approach improve multiple sclerosis ms patients diseasemodifying therapies dmts resistance results obtained different studies indicate ahsct increases life quality ms patients several factors known influenced successful rate ahsct patients ms individuals aged 40 years short duration ms disease demonstrated show better response ahsct administration furthermore treatment approach effective relapsing remitting ms rrms patients progressive ms pms different clinical trials revealed ahsct low density conditioning regimen suggested suitable candidate approach management ms several molecular cellular mechanisms known involved resetting immune system following ahsct infusion ms patients mechanisms play role depletion autoreactive lymphocytes immune system renewal present review discuss different clinical molecular aspects ahsct application alleviation ms symptomspmid33688164 pmcpmc7936693 doi102147 btts267277,0.0
radiological clinical value 7t mri evaluating 3tvisible lesions pharmacoresistant focal epilepsies front neurol 2021 mar 2 12591586 doi 103389 fneur2021591586 ecollection 2021abstractobjective recent fda approval first 7t mri scanner clinical diagnostic use october 2017 will likely increase utilization 7t epilepsy presurgical evaluation study aims accessing radiological clinical value 7t patients pharmacoresistant focal epilepsy 3tvisible lesions methods patients pharmacoresistant focal epilepsy included lesion preoperative standardofcare 3t mri also 7t research mri epilepsy protocol used acquisition 7t mri prospective visual analysis 7t mri performed experienced boardcertified neuroradiologist communicated patient management team clinical significance additional 7t findings assessed intracranial eeg iceeg ictal onset surgical resection postoperative seizure outcome histopathology subset lesions demarked arrows subsequent retrospective comparison 3t 7t 7 neuroradiologists using set quantitative scales lesion presence conspicuity boundary graywhite tissue contrast artifacts helpful sequence diagnosis congers kappa multiple raters performed chanceadjusted agreement statistics results total 47 patients included main pathology types focal cortical dysplasia fcd hippocampal sclerosis periventricular nodular heterotopia pvnh tumor polymicrogyria pmg 7t detected additional smaller lesions 19 9 47 patients extensive abnormalities pmg pvnh however additional findings necessarily epileptogenic 3t7t comparison neuroradiologist team showed lesion conspicuity lesion boundary significantly better 7t p 0001 particularly fcd pvnh pmg chanceadjusted agreement within fair range lesion presence conspicuity boundary graywhite contrast significantly improved 7t p 0001 significantly artifacts encountered 7t p 0001 significance patients 3tvisible lesions 7t mri may better elucidate extent multifocal abnormalities pvnh pmg providing potential targets improve iceeg implantation patients fcd pvnh pmg likely benefit 7t due improved lesion conspicuity boundary pathologies anteroinferior temporal regions likely benefit less due artifactspmid33737901 pmcpmc7960771 doi103389 fneur2021591586,0.0
case report exome sequencing achieved definite diagnosis chinese family muscle atrophy background due large genetic phenotypic heterogeneity conventional workup charcotmarietooth cmt diagnosis often underpowered leading diagnostic delay even lack diagnosis present study explored bioinformatics analysis wholeexome sequencing wes data can used diagnose patients cmt disease efficientlycase presentationthe proband 29yearold female presented severe amyotrophy distal skeletal deformity plagued family 20 years since 5yearold aberrant symptoms detected speaking hearing vision intelligence similar symptoms manifested younger brother parents older brother showed normal uncover genetic causes disease performed exome sequencing proband parents subsequent bioinformatics analysis kggseq platform sanger sequencing identified novel homozygous gdap1 nonsense mutation c218c g pser73 responsible family genetic finding led quick diagnosis cmt type 4a cmt4a confirmed nerve conduction velocity electromyography examination patientsconclusionsthe patients severe muscle atrophy distal skeletal deformity caused novel homozygous nonsense mutation gdap1 c218c g pser73 diagnosed cmt4a finally study expanded mutation spectrum cmt disease demonstrated affordable wes effectively employed clinical diagnosis unexplained phenotypes,0.0
validation threeitem fatigue severity scale patients substance use disorder cohort study norway period 20162020 background little attention paid customising fatigue questionnaires patients substance use disorders suds present study aims validate shorten nineitem fatigue severity scale fss9 visual analogue fatigue scale vafs use populationmethodswe used data nested cohort annual health assessments responses fss9 vafs period 20162020 917 health assessments collected 655 patients sud bergen stavanger norway total 225 patients answered health assessment least twice defined baseline first annual health assessment health assessments sorted chronologically per patient checked internal consistency used longitudinal confirmatory factor analysis cfa linear mixed model lmm analysis validate shorten fss9 vafsresultsthe internal consistency fss9 excellent cronbachs 094 baseline 093 second annual health assessment shortening fss9 threeitem fss fss3 items 57 cronbachs 087 baseline 084 second health assessment internal consistency affected vafs added fss3 fss9 longitudinal cfa model showed wellfitting model fss3 2 1333 degree freedom 8 p 0101 lmm analysis showed equal linear changes individual level fss3 slope 000 p 005 fss9 slope 001 p 005 health assessmentsconclusionthe fss9 shortened fss3 high validity reliability patients suds addition vafs provide much added variability,0.0
prospective multicenter study assessing musiqol validity among arabicspeaking ms patients treated subcutaneous interferon 1a mult scler int 2021 mar 2 20216681431 doi 101155 2021 6681431 ecollection 2021abstractfew studies examine healthrelated quality life hrqol arabicspeaking multiple sclerosis ms patients however hrqol tools short form36 qol instrument sf36 multiple sclerosis international qol musiqol questionnaire validated languages primary objective study prospectively assess hrqol using musiqol questionnaire among arabicspeaking ms patients treated subcutaneous interferon sc ifn 1a 12 months part prospective multinational multicenter cohort study patients clinical parameters hrqol assessed baseline 6 months 12 months changes musiqol total subdomain scores compared using friedman test correlation musiqol total score expanded disability status score edss also evaluated total 439 patients four arabicspeaking countries included mean age 3244 034 years 715 female 631 education level university mean ms duration 413 012 years mean age first attack 2735 026 years mean baseline edss score 205 004 musiqol total score significantly improved 6 months however diminished 12 months 6567 08 baseline vs 6721 079 6 months 6575 08 12 months p 00015 several aspects patients hrqol including activity daily living physical wellbeing symptoms coping improved overall hrqol measured using sf36 remained generally unchanged time p 0215 statistically significant inverse relationship change edss score time change overall musiqol score time summary findings confirm utility using musiqol assessing changes hrqol treatment sc ifn 1a arabicspeaking patients mspmid33747564 pmcpmc7943271 doi101155 2021 6681431,0.0
editorial quot insideoutquot vs quot outsideinquot paradigms multiple sclerosis etiopathogenesis front cell neurosci 2021 mar 1 15666529 doi 103389 fncel2021666529 ecollection 2021no abstractpmid33732113 pmcpmc7957074 doi103389 fncel2021666529,0.0
emerging role chondroitin sulfate proteoglycan family neurodegenerative diseases rev neurosci 2021 mar 1 doi 101515 revneuro20200146 online ahead printabstractchondroitin sulfate cs kind linear polysaccharide covalently linked proteins form proteoglycans chondroitin sulfate proteoglycans cspgs consist core protein one cs chains covalently attached cspgs precisely regulated exert variety physiological functions binding adhesion molecules growth factors widely distributed nervous system human body cspgs contribute major component extracellular matrix ecm play important role development maturation nervous system well pathophysiological response damage central nervous system cns 30 types cspgs review covers roles important ones including versican aggrecan neurocan ng2 pathogenesis neurodegenerative diseases including alzheimers disease parkinsons disease amyotrophic lateral sclerosis multiple sclerosis updated reports treatment neurodegenerative diseases involving cspgspmid33655733 doi101515 revneuro20200146,0.0
bloodbrain barrier resealing neuromyelitis optica occurs independently astrocyte regeneration j clin invest 2021 mar 1 131 5 141694 doi 101172 jci141694abstractapproximately 80 neuromyelitis optica spectrum disorder nmosd patients harbor serum antiaquaporin4 autoantibodies targeting astrocytes cns crucial nmosd lesion initiation disruption bloodbrain barrier bbb allows entrance abs serum complement cns target new nmosd therapies astrocytes important functions bbb maintenance however influence loss role immune cell infiltration bbb permeability nmosd yet investigated using experimental model targeted nmosd lesions rats demonstrate astrocyte destruction coincides transient disruption bbb selective loss occludin tight junctions noteworthy bbb integrity reestablished astrocytes repopulate rather persistent astrocyte loss polymorphonuclear leukocytes pmns main mediators bbb disruption depletion preserves bbb integrity prevents astrocyte loss inhibition pmn chemoattraction activation proteolytic function reduces lesion size summary data support crucial role pmns bbb disruption nmosd lesion development rendering recruitment activation promising therapeutic targetspmid33645550 doi101172 jci141694,0.0
juvenile primary fibromyalgia syndrome epidemiology etiology pathogenesis clinical manifestations diagnosis abstractjuvenile primary fibromyalgia syndrome jpfs chronic musculoskeletal pain syndrome affecting children adolescents commonly adolescent girls syndrome multifactorial etiology altered central pain processing playing important role hallmark symptom severe widespread musculoskeletal pain symptoms include sleep mood disturbances headaches stiffness subjective joint swelling physical examination can reveal multiple tender points diagnosis clinical defined criteria early diagnosis intervention important part review discuss epidemiology etiology pathogenesis clinical manifestations diagnosis jpfs part two will focus treatment prognosis,0.0
health literacy multiple sclerosis patients concept analysis using evolutionary method j caring sci 2021 mar 1 10 1 4956 doi 1034172 jcs2021010 ecollection 2021 marabstractintroduction health literacy one effective factors health promotion chronic patients however little attention paid exact clear definition health literacy ever accessible chronic diseases study conducted aim defining clarifying attributes antecedents consequences health literacy multiple sclerosis ms patients methods rodgers evolutionary method concept analysis used clarify concept health literacy ms patients literature review conducted key terms multiple sclerosis health literacy information literacy functional health health education health promotion health behavior eight hundred sixty papers period 1980 2019 found finally 23 articles texts selected analysis data analysis carried using thematic analysis results health literacy ms patients multidimensional concept forth attributes health information evaluation understand disease related issues reading skills capacity use knowledge ability read comprehend interacting health personnel interacting peers antecedents improved selfcare health promotion medication adherence decreased use health care services consequences attributes found conclusion findings can add knowledge concept health literacy ms patients also health care professionals can use deeper understanding concept health literacy providing care plan ms patientspmid33816385 pmcpmc8008227 doi1034172 jcs2021010,0.0
consistency applicability different brief screen instrument cognitive function elderly population background screening cognitive impairment ci often hampered lack consensus screening instrument use aim assess consistence applicability different ci screening toolsmethodin crosssectional study october 2017 september 2018 7 communities shanghai china elder 60 residential volunteers history major cardiovascular diseases cancers comorbidities known affect cognitive functions recruited participants underwent tests 7 cognitive function screening instruments multivariate linear regressions performed test correlations demographic characteristics including gender age education marital status cognitive test scores minimental state examination mmse score adjusted according correlation coefficients used detect ci cutoff 24 cognitive function scores compared participants without ci addition pearsons correlation test used detect association different test scoresresults172 participants relatively low education levels included age education showed significant association cognitive test scores using adjusted mmse 396 participants identified ci percentage 872 adjusted montreal cognitive assessment moca cutoff 26 used analysis abnormal test scores showed mmse highest percentage valid data 988 moca isaacs test verbal fluency vf score correlation scores mmse significantly associated vf mocaconclusionsmmse may still present applicable tools quick screen cognitive functions especially environmental conditions may interfere participants attention,0.0
outcomes intraarticular calcaneal fractures surgical treatment 114 consecutive cases maximum care trauma center background aim retrospective monocentric study investigate outcomes surgically treated intraarticular calcaneus fractures maximum care trauma centermethodsone hundred forty patients undergone surgery intraarticular calcaneal fractures 2002 2013 included one hundred fourteen cases 129 fractures eligible participate study 80 available clinical radiological followup 34 patients followed telephone interview outcome measures included american orthopaedic foot ankle society aofas hindfoot score short form 36 health status survey sf36 complications subsequent surgeriesresultsmean followup 91 months range 12183 overall complication rate 29 37 129 ft disturbed wound healing 11 infection 5 occurred commonly nonunion 4 occurred smokers p 002 high rate posttraumatic subtalar arthritis 77 need subsequent subtalar fusion 18 without independent risk factors subsequent subtalar fusion found revision rate high 60 primary fusion mean aofashindfoot score 74 sanders 99 sanders ii 74 sanders iii 77 sanders iv 70 postoperative boehler angle improved significantly subgroups p 001 patients decreased boehler angle postoperative images followup significantly lower aofas hindfoot scores p 001 conclusionsour data can aid decisionmaking treatment calcaneal fractures advocate use primary subtalar fusion caution due high revision rate smoking status always consideredlevel evidence level iii retrospective cohort study,0.0
neuronal hibernation following hippocampal demyelination acta neuropathol commun 2021 mar 1 9 1 34 doi 101186 s40478021011309abstractcognitive dysfunction occurs greater 50 individuals multiple sclerosis ms hippocampal demyelination prominent feature postmortem ms brains hippocampal atrophy correlates cognitive decline ms patients cellular molecular mechanisms responsible neuronal dysfunction demyelinated hippocampi fully understood investigate mouse model hippocampal demyelination twelve weeks treatment oligodendrocyte toxin cuprizone demyelinates 90 hippocampus causes decreased memory learning longterm potentiation ltp hippocampal ca1 pyramidal neurons considered major cellular readout learning memory mammalian brain acute slices establish hippocampal demyelination abolishes ltp excitatory postsynaptic potentials ca1 neurons presynaptic function schaeffer collateral fibers preserved demyelination also reduced ca2+mediated firing hippocampal neurons vivo using threedimensional electron microscopy investigated number shape mushroom stubby thin postsynaptic densities psds dendritic spines facilitate ltp hippocampal demyelination alter number dendritic spines surprisingly dendritic spines appeared mature demyelinated hippocampi significant increase mushroomshaped spines perforated psds astrocyte participation tripartite synapse rna sequencing experiments identified 400 altered transcripts demyelinated hippocampi gene transcripts regulate myelination synaptic signaling astrocyte function innate immunity altered demyelinated hippocampi hippocampal remyelination rescued synaptic transmission ltp majority gene transcript changes establish ca1 neurons projecting demyelinated axons silence dendritic spines hibernate state may protect demyelinated axon facilitates functional recovery following remyelinationpmid33648591 doi101186 s40478021011309,1.0
congruent microbiome signatures fibrosisprone autoimmune diseases igg4related disease systemic sclerosis genome med 2021 feb 28 13 1 35 doi 101186 s13073021008537abstractbackground immunoglobulin g4related disease igg4rd systemic sclerosis ssc rare autoimmune diseases characterized presence cd4+ cytotoxic t cells blood well inflammation fibrosis various organs established etiologies similar autoimmune diseases gut microbiome might encode diseasetriggering diseasesustaining factorsmethods gut microbiomes igg4rd ssc patients well healthy individuals recent antibiotic treatment studied metagenomic sequencing stool dna de novo assemblybased taxonomic functional characterization followed association accessory gene set enrichment analysis applied describe microbiome changes associated diseasesresults microbiomes igg4rd ssc patients distinctly separated healthy controls numerous opportunistic pathogenic clostridium typically oral streptococcus species significantly overabundant alistipes bacteroides butyrateproducing species depleted two diseases compared healthy controls accessory gene content analysis species revealed enrichment th17activating eggerthella lenta strains igg4rd ssc preferential colonization homocysteineproducing strain clostridium bolteae ssc overabundance classical mevalonate pathway hydroxyproline dehydratase fibronectinbinding protein disease microbiomes reflects potential functional differences host immune recognition extracellular matrix utilization associated fibrosis strikingly majority species differentially abundant igg4rd ssc compared controls showed directionality diseases compared multiple sclerosis rheumatoid arthritis gut microbiomes igg4rd ssc showed similar signatures contrast differentially abundant taxa facultative anaerobes consistently identified inflammatory bowel diseases suggesting microbial signatures igg4rd ssc result mucosal inflammation decreased anaerobismconclusions results provide initial characterization gut microbiome ecology fibrosisprone igg4rd ssc reveal microbial functions offer insights pathophysiology rare diseasespmid33648559 doi101186 s13073021008537,0.0
methylxanthines neurodegenerative diseases update nutrients 2021 feb 28 13 3 803 doi 103390 nu13030803abstractmethylxanthines mtx purine derived xanthine derivatives whereas naturally occurring methylxanthines like caffeine theophylline theobromine widely consumed food several synthetic also nonsynthetic methylxanthines used pharmaceuticals particular treating airway constrictions besides wellestablished bronchoprotective effects methylxanthines also known antiinflammatory antioxidative properties mediate changes lipid homeostasis neuroprotective effects known molecular mechanisms include adenosine receptor antagonism phosphodiesterase inhibition effects cholinergic system wnt signaling histone deacetylase activation gene regulation affecting several pathways associated neurodegenerative diseases via different pleiotropic mechanisms due moderate side effects intake methylxanthines suggested interesting approach dealing neurodegeneration especially past years impact methylxanthines neurodegenerative diseases extensively studied several new aspects elucidated review summarize findings methylxanthines linked alzheimers disease parkinsons disease multiple sclerosis since 2017 focusing epidemiological clinical studies addressing underlying molecular mechanisms cell culture experiments animal studies order assess neuroprotective potential methylxanthines diseasespmid33671099 doi103390 nu13030803,1.0
telehealth multiple sclerosis clinical care research curr neurol neurosci rep 2021 feb 28 21 4 14 doi 101007 s11910021011034abstractpurpose review covid19 pandemic provided us unique opportunity experiment telehealth evaluate benefits limitations review discusses impact telehealth multiple sclerosis ms care research adults childrenrecent findings telehealth visits ms patients shown reduce missed workdays costs patients brief telephonebased counseling may associated better adherence diseasemodifying therapy although results multiple homebased telerehabilitation people ms equivocal overall patients providers reported high levels satisfactions telehealth several remote disability measures numerous technological tools emerged use remote ms research care major challenges telehealth include limitations performing complete neurologic exam disparities access telehealth amongst vulnerable populations limited access virtual platforms following rapid expansion telehealth pandemic highly likely will continue embrace benefits valuable tool future directions improving telehealth include evidencebased research diagnostic accuracy neuroimmunology reducing disparities access telehealthpmid33646409 doi101007 s11910021011034,0.0
positron emission tomography imaging vivo measuring myelin content lysolecithin rat model multiple sclerosis j vis exp 2021 feb 28 168 doi 103791 62094abstractmultiple sclerosis ms neuroinflammatory disease expanding axonal neuronal degeneration demyelination central nervous system leading motor dysfunctions psychical disability cognitive impairment ms progression positron emission tomography pet imaging technique able quantify vivo cellular molecular alterations radiotracers affinity intact myelin can used vivo imaging myelin content changes time possible detect either increase decrease myelin content means imaging technique can detect demyelination remyelination processes central nervous system protocol demonstrate use pet imaging detect myelin changes lysolecithin rat model model focal demyelination lesion induced stereotactic injection ie model multiple sclerosis disease 11cpib pet imaging performed baseline 1 week 4 weeks stereotaxic injection lysolecithin 1 right striatum 4 l corpus callosum 3 l rat brain allowing quantification focal demyelination injection site 1 week remyelination process injection site 4 weeks myelin pet imaging interesting tool monitoring vivo changes myelin content useful monitoring demyelinating disease progression therapeutic responsepmid33720130 doi103791 62094,1.0
social anxiety obsessivecompulsive disorder common among persons multiple sclerosis king abdulaziz medical city riyadh cureus 2021 feb 28 13 2 e13619 doi 107759 cureus13619abstractbackground multiple sclerosis ms associated physical disability disturbed psychosocial functioning young people many psychological psychiatric comorbidities reported ms objective determine frequency social anxiety disorder sad obsessivecompulsive disorder ocd among ms patients relation ms severity methods crosssectional survey conducted adult ms cohort yalebrown obsessivecompulsive scale ybocs social phobia inventory spin used determine presence severity ocd sad statistical package social sciences spss version 22 ibm corp armonk ny used statistical analysis mannwhitney u test logistic regression used assess association two diseases severity ms results total 145 persons ms pwms studied mean age 335 85 years mean duration ms 72 51 years majority 741 women 573 married 63 college education 50 belonged higher middleclass socioeconomic strata relapsingremitting multiple sclerosis common type ms 922 mean expanded disability status scale edss score 224 219 sad reported 269 ocd reported 31 cohort pwms walking difficulty wheelchairbound statistically significant increased risk sad p 0036 direct association msrelated disability ocd however pwms sad likely concomitant ocd t468 pvalue 0001 95 ci 047116 increasing disability associated higher chances developing social anxiety turn ocd t339 pvalue 0001 95 ci 066252 conclusions social anxiety obsessivecompulsive disorders present nearly onethird pwms impaired walking wheelchair dependence associated social anxiety pwms sad likely obsessivecompulsive disorderpmid33816018 pmcpmc8010157 doi107759 cureus13619,0.0
dynamics central remyelination treatment evolution model multiple sclerosis optic coherence tomography int j mol sci 2021 feb 28 22 5 2440 doi 103390 ijms22052440abstractthe need remyelinating drugs essential healing disabling diseases multiple sclerosis ms one reasons lack class therapies impossibility monitor remyelination vivo utmost importance perform effective clinical trials show optical coherence tomography oct cheap noninvasive technique commonly used ophthalmology may used assess remyelination vivo ms patients pioneer approach validates oct technique study remyelination optic nerve reflects occurring nonaccessible central nervous system cns structures like spinal cord study used orally bioavailable small molecule vp315 confirming therapeutical potential neuroprotective antiinflammatory probably remyelinating drug ms altogether results confirm usefulness oct monitor efficacy remyelinating therapies vivo underscore relevance vp315 potential disease modifying drug ms therapypmid33671012 doi103390 ijms22052440,1.0
effectiveness film health communication tool improve perceptions attitudes multiple sclerosis mult scler j exp transl clin 2021 feb 27 7 1 2055217321995947 doi 101177 2055217321995947 ecollection 2021 janmarabstractbackground health communication tools like film capable reducing health disparities effective addressing negative illness perceptions ms hispanics latinxobjective test feasibility using culturally appropriate short narrative film examine illness perceptions overtime attitudes hispanics latinx affected msmethods participants assigned view short narrative film n 130 n 106 brief illness perception questionnaire bipq used examine illness perceptions baseline one three months focus groups conducted 6 months measures sociocultural integration obtained individual group bipq domains evaluated time using paired sample ttest multivariate linear regression used examine predictors bipq changeresults positive perception treatment p 00001 understanding p 00003 seen 3 months exposed film focus groups effective highlighting perceived disease prognosis family support awareness ms contributes attitudes exposure film found strongest predictor beta631 p 001 bipq change three monthsconclusion results provide support short narrative film ms hispanics latinx feasible intervention change perceptions ms positive viewpmid33717502 pmcpmc7923991 doi101177 2055217321995947,0.0
dying forward hypothesis als tracing history brain sci 2021 feb 27 11 3 300 doi 103390 brainsci11030300abstractthe site origin amyotrophic lateral sclerosis als although unsettled increasingly recognized corticofugal dyingforward process primarily starting corticomotoneuronal system variety iterations concept date back 150 years recently hallmark tar dnabinding protein 43 tdp43 pathology seen 95 patients als shown largely restricted corticofugal projecting neurons dying forward possibly soluble toxic cytoplasmic tdp43 enter axoplasm betz cells subsequently causing dysregulation nuclear protein lower brainstem spinal cord anterior horn cells disease progresses cortical involvement als becomes widespread including starting frontotemporal dementia implying broader view als brain disease onset motor premotor cortices considered nidus edge multiple cortical networks eventually become disrupted causing failure widespread cortical connectomepmid33673524 doi103390 brainsci11030300,0.0
exploring polypharmacy phenomenon newly diagnosed relapsingremitting multiple sclerosis cohort ambispective singlecentre study ther adv chronic dis 2021 feb 27 122040622320983121 doi 101177 2040622320983121 ecollection 2021abstractaims aimed examine frequency polypharmacy large cohort patients time diagnosis relapsingremitting multiple sclerosis rrms explore effects discontinuation first diseasemodifying treatment dmt using survival analysismethods cohort ambispective singlecentre study enrolled rrms patients starting first dmt 1st january 2013 31st december 2015 according number medicines prescribed except dmts divided patients three groups nopoly rrms minorpoly rrms one three medications majorpoly rrms three medications results total 392 rrms patients enrolled mean age 411 minorpoly rrms group included 61 patients 156 majorpoly rrms group included 112 286 individuals groups older higher median body mass index bmi patients nopoly rrms group p 005 upon multinomial regression analysis older age onset associated minor major polypharmacy 1050 ci 10101093 p 0015 1063 ci 10261101 p 0001 respectively higher bmi associated major polypharmacy 1186 ci 118129 p 0001 rates discontinuation first dmt similar among three groups 507 nopoly rrms 508 minorpoly rrms 533 majorpoly rrms p 0264 logrank test differences among three groups p 0834 conclusion polypharmacy common older rrms patients high bmipmid33717425 pmcpmc7923988 doi101177 2040622320983121,0.0
safety efficacy daclizumab beta patients relapsing multiple sclerosis 5year openlabel study extend final results following early termination ther adv neurol disord 2021 feb 26 141756286420987941 doi 101177 1756286420987941 ecollection 2021abstractbackground extend nct01797965 openlabel extension study evaluated safety efficacy daclizumab beta participants relapsing multiple sclerosis ms completed randomized decide studymethods eligible participants received either daclizumab beta interferon beta1a decide received daclizumab beta 150 mg subcutaneously every 4 weeks 5 years extend followed 24 weeks postdosing followup safety tolerability evaluated clinical efficacy magnetic resonance imaging mri extend terminated ahead schedule sponsorsresults total safety population n 1203 received least one dose daclizumab beta extend decide extend combined periods median number doses daclizumab beta 53 median time treatment 196 weeks 24 september 2018 end study 110 1203 9 participants completed protocolspecified treatment period 1101 1203 92 experienced adverse event ae commonly reported aes ms relapse nasopharyngitis upper respiratory tract infection hepatic events 18 cutaneous events 45 infections 62 common treatmentrelated aes incidence serious aes 29 commonly ms relapse infections incidence immunemediated disorders 2 three seven encephalitis two six deaths considered treatment related participants received continuous daclizumab beta throughout decide extend treatment effects clinical mri outcomes maintained 6 yearsconclusion results combined decideextend study elucidate outcomes longerterm treatment daclizumab beta clinical trial setting underscore importance pharmacovigilance immunomodulatory therapies realworld settingpmid33737954 pmcpmc7934044 doi101177 1756286420987941,0.0
multimodal fusion eegfnirs mutual informationbased hybrid classification framework biomed opt express 2021 feb 26 12 3 16351650 doi 101364 boe413666 ecollection 2021 mar 1abstractmultimodal data fusion one current primary neuroimaging research directions overcome fundamental limitations individual modalities exploiting complementary information different modalities electroencephalography eeg functional nearinfrared spectroscopy fnirs especially compelling modalities due potentially complementary features reflecting electrohemodynamic characteristics neural responses however current multimodal studies lack comprehensive systematic approach properly merge complementary features multimodal data identifying systematic approach properly fuse eegfnirs data exploit complementary potential crucial improving performance paper proposes framework classifying fused eegfnirs data feature level relying mutual informationbased feature selection approach respect complementarity features goal optimize complementarity redundancy relevance multimodal features respect class labels belonging pathological condition healthy control nine amyotrophic lateral sclerosis als patients nine controls underwent multimodal data recording visuomental task multiple spectral temporal features extracted fed feature selection algorithm followed classifier selected optimized subset features crossvalidation process results demonstrated considerably improved hybrid classification performance compared individual modalities compared conventional classification without feature selection suggesting potential efficacy proposed framework wider neuroclinical applicationspmid33796378 pmcpmc7984774 doi101364 boe413666,0.0
hepatitis c disease modifying therapy fingolimod relapsing remitting multiple sclerosis diagnosis treatment bmj case rep 2021 feb 26 14 2 e238167 doi 101136 bcr2020238167abstractwe present case 48yearold woman relapsing remitting multiple sclerosis ms switched disease modifying therapy copaxone fingolimod due clinical radiological ms disease progression unexpectedly 25 years stable ms symptoms liver function tests lfts noted deranged lfts routine testing additional investigations showed hepatitis c positivity genotype 3 likely case hepatitis c reactivation secondary prolonged immunosuppressive effects fingolimod although increased risk viral reactivation related varicella zoster virus known occur fingolimod treatment knowledge second case hepatitis c disease activity reported fingolimod treatment like raise awareness hepatitis c viral reactivation possible complication prolonged immunosuppression fingolimodpmid33637491 doi101136 bcr2020238167,0.0
prediction singlenucleotide polymorphisms within micrornas binding sites neuronal genes related multiple sclerosis preliminary study adv biomed res 2021 feb 26 108 doi 104103 abrabr_143_20 ecollection 2021abstractbackground different genetic variants including singlenucleotide polymorphisms snps present microrna recognition elements mres within 3utr genes can affect mirnamediated gene regulation susceptibility variety human diseases multiple sclerosis ms disease central nervous system since expression many genes associated ms controlled micrornas mirnas aim study analyze snps within mirna binding sites neuronal genes associated msmaterials methods fiftyseven neuronal genes related ms achieved using dbgap david disgenet oviddatabases 3utr candidate genes assessed snps mirnas target prediction databases used predicting mirna binding sitesresults three hundred eight snps minor allele frequency 005 identified mirna binding sites 3utr 44 genes among 42 snps 22 genes mirna binding sites mirna prediction tools suggested 71 putative mirnas binding sites genes moreover silico analysis predicted 22 mremodulating snps 22 mrecreating snps 3utr candidate genesconclusions candidate mresnps can alter mirnas binding sites mrna gene regulation therefore genetic variants mirnas might involved ms susceptibility pathogenesis hence valuable functional verification investigationpmid33959565 pmcpmc8095259 doi104103 abrabr_143_20,0.0
differential gene expression patterns blood cerebrospinal fluid multiple sclerosis neurobehcet disease front genet 2021 feb 26 12638236 doi 103389 fgene2021638236 ecollection 2021abstractinflammatory demyelinating disorders central nervous system debilitating conditions young adult focus multiple sclerosis ms neurobehet disease nbd ms autoimmune disorder central nervous system nbd neurological manifestation idiopathic chronic relapsing multisystem inflammatory disease behet disease diagnosis ms nbd relies clinical symptoms magnetic resonance imaging laboratory tests first onset clinical imaging similarities two disorders may occur making differential diagnosis challenging delaying appropriate management aiming identify additional discriminating biomarker patterns measured compared gene expression broad panel selected genes blood cerebrospinal fluid csf cells patients suffering nbd ms non inflammatory neurological disorders nind reach aim bivariate multivariate analysis applied principal analysis component pca highlighted distinct profiles nbd ms controls transcription factors foxp3 blood along il4 il10 il17 expressions parameters main contributor segregation ms nbd clustering moreover parameters related cellular activation inflammatory cytokines within csf clearly differentiate two inflammatory diseases controls proceeded roc analysis order identify distinctive parameters inflammatory neurological disorders latter analysis suggested il17 cd73 blood well il1 il10 csf discriminating parameters ms nbd conclude combined multidimensional analysis blood csf suggests distinct mechanisms governing pathophysiology two neuroinflammatory disorderspmid33719347 pmcpmc7954360 doi103389 fgene2021638236,1.0
tolllike receptor9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation murine model multiple sclerosis sci rep 2021 feb 26 11 1 4735 doi 101038 s41598021840230abstractearly innate education hematopoietic progenitors within bone marrow bm stably primes either trained immunity instead immunoregulatory functions herein demonstrate vivo vitro activation within bm via tolllike receptor9 generates population plasmacytoid dendritic cell pdc precursors cpgprepdcs unlike pdc precursors isolated pbsincubated bm pbsprepdcs endowed capacity halt progression ongoing experimental autoimmune encephalomyelitis cpg activation enhances selective migration pdc precursors inflamed spinal cord induces immediate production tgf migration enhanced levels il27 cpgprepdc derived tgf il27 ensure protection early late phases disease respectively spinal cords cpgprepdcprotected recipient mice display enhanced percentages hostderived pdcs expressing tgf well accumulation il10 producing b cells cd11c+ cd11b+ dendritic cells results reveal pdc precursors conferred stable therapeutic properties early innate activation within bm extend pdc lineage promising perspectives cell therapy autoimmune diseases innate activated hematopoietic precursor cellspmid33637789 doi101038 s41598021840230,0.0
seaweed diet prevention treatment neurodegenerative diseases mar drugs 2021 feb 26 19 3 128 doi 103390 md19030128abstractedible marine algae rich bioactive compounds therefore source bioavailable proteins long chain polysaccharides behave lowcalorie soluble fibers metabolically necessary minerals vitamins polyunsaturated fatty acids antioxidants marine algae used primarily gelling agents thickeners phycocolloids food pharmaceutical industries last century recent research revealed potential source useful compounds pharmaceutical medical cosmetic industries green red brown algae shown useful therapeutic properties prevention treatment neurodegenerative diseases parkinson alzheimers multiple sclerosis chronic diseases review listed described main components suitable diet patients diseases addition compounds derived macroalgae neurophysiological activities describedpmid33652930 doi103390 md19030128,0.0
dna methylation metaanalysis reveals cellular alterations psychosis markers treatmentresistant schizophrenia elife 2021 feb 26 10e58430 doi 107554 elife58430 online ahead printabstractwe performed systematic analysis blood dna methylation profiles 4 483 participants seven independent cohorts identifying differentially methylated positions dmps associated psychosis schizophrenia treatmentresistant schizophrenia psychosis cases characterized significant differences measures blood cell proportions elevated smoking exposure derived dna methylation data largest differences seen treatmentresistant schizophrenia patients implemented stringent pipeline metaanalyze epigenomewide association study ewas results across datasets identifying 95 dmps associated psychosis 1 048 dmps associated schizophrenia evidence colocalization regions nominated genetic association studies disease many schizophreniaassociated dna methylation differences present patients treatmentresistant schizophrenia potentially reflecting exposure atypical antipsychotic clozapine results highlight dna methylation data can leveraged identify physiological eg differential cell counts environmental eg smoking factors associated psychosis molecular biomarkers treatmentresistant schizophreniapmid33646943 doi107554 elife58430,0.0
brain activation changes walking adults without neurological disease systematic review metaanalysis functional nearinfrared spectroscopy studies brain sci 2021 feb 26 11 3 291 doi 103390 brainsci11030291abstract 1 functional nearinfrared spectroscopy fnirs provides useful tool monitoring brain activation changes walking adults neurological disorders combined dual task walking paradigms fnirs allows changes brain activation monitored individuals concurrently attend multiple tasks however differences dual task paradigms baseline coverage cortical areas presents uncertainty interpretation overarching findings 2 methods conducting systematic review 35 studies metaanalysis 75 effect sizes 17 studies adults without neurological disorders show performance obstacle walking serial subtraction letter generation tasks walking result significant increases brain activation prefrontal cortex relative standing walking baselines 3 results overall find letter generation tasks largest brain activation effect sizes relative walking significant differences dual task single task gait seen persons multiple sclerosis stroke 4 conclusions older adults neurological disease generally showed increased brain activation suggesting use attentional resources dual task walking lead increased fall risk mobility impairments prospero id 235228pmid33652706 doi103390 brainsci11030291,0.0
role natural killer cells autoimmune diseases front immunol 2021 feb 25 12622306 doi 103389 fimmu2021622306 ecollection 2021abstractnatural killer nk cells large granular lymphocytes differentiated common lymphoid progenitors discovered early 1970s members innate immunity initially defined strong cytotoxicity virusinfected cells important effector functions antitumoral immune responses nowadays nk cells classified among recently discovered innate lymphoid cell subsets capacity influence innate adaptive immune responses therefore can considered innate immune cells stands innate adaptive arms immunity nk cells dont express t b cell receptors recognized absence cd3 two major subgroups nk cells according differential expression cd16 cd56 cd16+cd56dim subset bestknown cytotoxic functions cd16cd56bright nk cell subset produces bunch cytokines comparable cd4+ t helper cell subsets another subset nk cells production interleukin il 10 named nk regulatory cells suppressive properties take part immuneregulatory responses activation nk cells determined delicate balance cellsurface receptors either activating inhibitory properties hand variety cytokines including il2 il12 il15 il18 influence nk cell activity nkderived cytokines cytotoxic functions induction apoptosis take part regulation immune responses contribute pathogenesis many immune mediated diseases including ankylosing spondylitis behets disease multiple sclerosis rheumatoid arthritis psoriasis systemic lupus erythematosus type1 diabetes dysregulation nk cells autoimmune disorders may occur multiple mechanisms thanks rapid developments biotechnology progressive research immunology enables better characterization cells delicate roles complex network immunity nk cells stand innate adaptive arms immunity bridge contribution inflammation immune regulation deserves intense investigations better understanding nkcell biology contribution exacerbation regulation inflammatory disorders requisite possible utilization multifaceted cells novel therapeutic interventionspmid33717125 pmcpmc7947192 doi103389 fimmu2021622306,0.0
symptom management patients multiple sclerosis primary care focus overlooked symptoms br j gen pract 2021 feb 25 71 704 139141 doi 103399 bjgp21x715193 print 2021no abstractpmid33632695 doi103399 bjgp21x715193,0.0
trends use sphingosine 1 phosphate agerelated diseases scientometric research study 19922020 j diabetes res 2021 feb 25 20214932974 doi 101155 2021 4932974 ecollection 2021abstractobjectives study designed explore intellectual landscape research application sphingosine 1 phosphate s1p agerelated diseases identify thematic development trends research frontiers areamethods scientometric research conducted analyzing bibliographic records retrieved web science wos sciexpanded database dated 1900 2020 countries institutions authors keyword occurrence analysis cooperation network analysis performed using citespace vosviewer softwareresults total 348 valid records included final dataset number publications frequency citations grown rapidly last ten years usa n 175 china n 42 germany n 37 three largest contributors global publications s1p aging medical university south carolina n 15 university california san francisco n 13 university toronto n 13 leading institutions field analysis showed early studies primarily focused mechanism s1p intervention ad s1p relevant metabolites remained longterm active area research recent studies focused interventions aimed improving retinal degeneration cardiomyopathy multiple sclerosis diabetes among othersconclusions worth mentioning manuscript first describe bibliometric analysis s1p application agerelated interventions study includes discussion 1 historical overview topic 2 main contributors journals countries institutes funding agencies authors 3 collaboration institutes authors 4 research hot spots zones 5 research trends frontiers will enable scholars understand current status s1p research agerelated diseasespmid33791388 pmcpmc7984909 doi101155 2021 4932974,0.0
csf cxcl13 concentrations solely dependent intrathecal production commentary chemokine cxcl13 serum csf bloodcsf barrier function fluids barriers cns 2021 feb 25 18 1 9 doi 101186 s12987021002445abstractpilz et al fluids barriers cns 177 2020 investigated csf cxcl13 concentrations influenced cxcl13 serum concentrations bloodcsf barrier bcsfb function comparing impact serum cxcl13 levels qalbumin csf albumin serum albumin csf cxcl13 among patients cns inflammation categorized cxcl13 negative low medium high among cxcl13 groups results showed correlation csf cxcl13 concentrations serum cxcl13 qalbumin authors argue contrast proteins cxcl13 passage across bcsfb occur regardless bcsfb function instead solely influenced intrathecal production contrast authors findings studies including noninflammatory neurological disorders nind n 62 multiple sclerosis ms patients observed significant correlation serum cxcl13 concentrations csf cxcl13 concentrations review several observations may underlie contrasting results including 1 impact serum cxcl13 concentrations csf cxcl13 patients lower intrathecal cxcl13 production thus lower cxcl13 concentrations ie nind ms 2 proposed diffusion dynamics small molecule cxcl13 across bcsfb 3 differing definitions negative versus elevated csf cxcl13 concentrations determined assays relative sensitivity conclusion argue patients moderately elevated csf cxcl13 concentrations serum cxcl13 concentrations influence csf cxcl13 levels thus appropriate corrections including incorporation csf serum ratios qalbumin values utilizedpmid33632258 doi101186 s12987021002445,0.0
expanded access multiple sclerosis teleneurology care following covid19 pandemic mult scler j exp transl clin 2021 feb 25 7 1 2055217321997467 doi 101177 2055217321997467 ecollection 2021 janmarabstractbackground teleneurology multiple sclerosis ms care considered feasible utilization limitedobjective describe existing teleneurology populations two academic ms centers changed covid19 pandemicmethods crosssectional study captured inperson teleneurology visits two academic ms centers january 2019 april 2020 compared group differences centers covidrelated changes using t chisquared kruskalwallis fisher exact testsresults 2268 patients completed 2579 teleneurology visits mean age 483 133 years 729 female precovid centers teleneurology populations similar age sex ms type disability level p 01 differed race 965 vs 807 white p 0001 ms treatment 491 vs 321 infusible p 0001 median distance center 72 vs 186 miles p 0001 postcovid centers teleneurology populations black 127 vs 437 p 0001 local median 345 vs 102 miles p 0001 patientsconclusion teleneurology visits 2019 reflected organizational local teleneurology reimbursement patterns centers postcovid19 changes illustrate potential payors policy change disparities access utilization remote care patients perception care quality value following shift warrants studypmid33738110 pmcpmc7934057 doi101177 2055217321997467,0.0
transcranial magnetic stimulation tms repetitive tms multiple sclerosis rev neurosci 2021 feb 25 doi 101515 revneuro20200140 online ahead printabstractmultiple sclerosis ms wellknown autoimmune disorder central nervous system constitutes major cause disability especially young individuals wide array pharmacological treatments available often proven ineffective ameliorating disease symptomatology slowing disease progress noninvasive nonpharmacological techniques gaining ground transcranial magnetic stimulation tms utilizes electric field generated magnetic coil stimulate neurons applied usually paired electroencephalography study underlying pathophysiology ms repetitive trains form repetitive transcranial magnetic stimulation rtms induce longlasting changes neuronal circuits review present available literature application tms rtms context ms emphasis therapeutic potential various clinical aspects also naming ongoing trials whose results anticipated futurepmid33641274 doi101515 revneuro20200140,0.0
singlecell immune repertoire transcriptome sequencing reveals clonally expanded transcriptionally distinct lymphocytes populate aged central nervous system mice proc biol sci 2021 feb 24 288 1945 20202793 doi 101098 rspb20202793 epub 2021 feb 24abstractneuroinflammation plays crucial role ageing various neurological conditions including alzheimers disease multiple sclerosis infection technical limitations however prevented integrative analysis lymphocyte immune receptor repertoires accompanying transcriptional states change age central nervous system leveraged singlecell sequencing simultaneously profile b cell receptor t cell receptor repertoires accompanying gene expression profiles young old mouse brains observed presence clonally expanded b t cells central nervous system aged male mice furthermore many b cells igm igd isotypes low levels somatic hypermutation integrating gene expression information additionally revealed distinct transcriptional profiles clonally expanded lymphocytes findings implicate clonally related t b cells cns elderly mice may contribute neuroinflammation accompanying homeostatic ageingpmid33622131 doi101098 rspb20202793,0.0
prevalence epileptic seizures multiple sclerosis large tertiary hospital australia mult scler j exp transl clin 2021 feb 24 7 1 2055217321989767 doi 101177 2055217321989767 ecollection 2021 janmarabstractrationale determine prevalence epileptic seizures multiple sclerosis ms australian tertiary hospital define clinical featuresmethods retrospectively analysed adult patients royal melbourne hospital electronically identified icd codes ms seizures epilepsy 1996 2019 utilising paper electronicbased recordsresults 2 125 ms patients identified 16 075 experienced epileptic seizures mean followup period 129 years median age ms diagnosis sd 38 93 years four patients relapsing remitting ms 25 10 secondary progressive ms 635 2 primary progressive ms 125 twothirds patients seizure onset following diagnosis ms majority advanced disease approximate edss 6 time seizure onset focal onsetseizures occurred 875 patients seizuresconclusion estimated prevalence seizures cohort lower previous studies 075 vs 24 cases seizures occurred diagnosis ms context advanced disease studies required determine ms disease modifying treatments reduce risk seizures cohortpmid33708413 pmcpmc7907940 doi101177 2055217321989767,0.0
mesenchymal stem cells neurological disorders adv sci weinh 2021 feb 24 8 7 2002944 doi 101002 advs202002944 ecollection 2021 aprabstractneurological disorders becoming growing burden society ages compelling need address spiraling problem stem cellbased regenerative medicine becoming increasingly attractive approach designing therapies disorders unique characteristics mesenchymal stem cells mscs make among sought cell sources researchers extensively studied modulatory properties mscs engineering labeling delivery methods brain first part review provides overview studies application mscs various neurological diseases including stroke traumatic brain injury spinal cord injury multiple sclerosis amyotrophic lateral sclerosis alzheimers disease huntingtons disease parkinsons disease less frequently studied clinical entities second part stem cell delivery brain focused fundamental still understudied problem needs overcome apply stem cells brain diseases successfully value cell engineering also emphasized facilitate msc diapedesis migration homing brain areas affected disease implement precision medicine paradigms stem cellbased therapiespmid33854883 pmcpmc8024997 doi101002 advs202002944,0.0
tumor therapy landscape synthetic lethality nat commun 2021 feb 24 12 1 1275 doi 101038 s41467021215442abstractsynthetic lethality emerging important cancer therapeutic paradigm comprehensive selective treatment opportunities various tumors yet explored develop synthetic lethality knowledge graph slkg presenting tumor therapy landscape synthetic lethality sl synthetic dosage lethality sdl slkg integrates largescale entity different tumors drugs drug targets exploring comprehensive set sl sdl pairs overall therapy landscape prioritized identify best repurposable drug candidates drug combinations literature supports vitro pharmacologic evidence clinical trial records finally cladribine fdaapproved multiple sclerosis treatment drug selected identified repurposable drug treating melanoma cdkn2a mutation vitro validation serving demonstrating slkg utility example novel tumor therapy discovery collectively slkg forms computational basis uncover cancerspecific susceptibilities therapy strategies based principle synthetic lethalitypmid33627666 doi101038 s41467021215442,0.0
smartphonebased symboldigit modalities test reliably captures brain damage multiple sclerosis npj digit med 2021 feb 24 4 1 36 doi 101038 s4174602100401yabstractas burden neurodegenerative diseases increases timelimited clinic encounters allow quantification complex neurological functions patientcollected digital biomarkers may remedy provide reliable information however psychometric properties digital tools remain largely unassessed developed smartphone adaptation cognitive test symboldigit modalities test sdmt randomizing tests symbolnumber codes testing sequences smartphone sdmt showed comparable psychometric properties 154 multiple sclerosis ms patients 39 healthy volunteers hv eg smartphone sdmt achieved slightly higher correlations cognitive subscores neurological examinations brain injury measured mri r2 075 rho 083 p 00001 traditional sdmt mathematical adjustment motoric disability dominant hand measured another smartphone test compensates disadvantage touchbased test averaging granular home measurements digital biomarker also increases accuracy identifying true neurological declinepmid33627777 doi101038 s4174602100401y,0.0
prevalence seizure epilepsy patients multiple sclerosis systematic review metaanalysis int j prev med 2021 feb 24 1214 doi 104103 ijpvmijpvm_75_20 ecollection 2021abstractbackground seizure epilepsy among initial symptoms multiple sclerosis ms yet different prevalence rates reported previous studies goal systematic review estimate pooled prevalence seizure epilepsy patients msmethods searched pubmed scopus embase web science google scholar gray literature including references identified studies conference abstracts published october 2019 search strategy included mesh terms text words epilepsies seizure disorder seizure disorders awakening epilepsy epilepsy awakening epilepsy cryptogenic cryptogenic epilepsies cryptogenic epilepsy epilepsies cryptogenic epilepsy seizure multiple sclerosis sclerosis multiple sclerosis disseminated disseminated sclerosis ms multiple sclerosis multiple sclerosis acute fulminating results literature review resulted 4860 articles 2593 articles remained eliminating duplicates final analysis 39 articles included 9 conference abstracts pooled prevalence seizure ms cases 2 95 confidence interval ci 13 i2 918 p 0001 pooled prevalence epilepsy ms cases 3 95 ci 24 i2 929 p 0001 pooled prevalence epilepsy asia europe america 6 3 3 respectively level heterogeneity decreased subgroup analysis asian american subgroups metaregression analysis showed continent source heterogeneity coefficient 0007 p 06 conclusions result systematic review shows pooled prevalence seizure epilepsy among ms patients 2 3 respectivelypmid34084311 pmcpmc8106278 doi104103 ijpvmijpvm_75_20,0.0
early mri outcomes participants first clinical demyelinating event risk multiple sclerosis oraclems study mult scler j exp transl clin 2021 feb 24 7 1 2055217321990852 doi 101177 2055217321990852 ecollection 2021 janmarabstractbackground phase 3 96week oraclems study cladribine tablets 10 mg 35 525 mg kg cumulative dosage two years significantly reduced lesions associated multiple sclerosis versus placebo participants following first clinical demyelinating event fcde objective determine timing effects cladribine tablets lesion activity assessed magnetic resonance imaging mri methods post hoc analysis assessed effect cladribine tablets versus placebo oraclems secondary mri endpoints including t1 gadoliniumenhancing gd+ new enlarging t2 lesions combined unique active lesions assessed mri scans performed screening every 3 months thereafterresults compared placebo cladribine tablets 35 mg kg treatment appeared lead trend reductions mean number t1 gd+ lesions week 13 first postbaseline scan 037 vs 100 new enlarging t2 020 vs 101 combined unique active 029 vs 191 lesions week 24 low lesion counts maintained cladribine tablets throughout 96 weeks similar results observed 525 mg kg dosageconclusion participants fcde cladribine tablets appeared reduce lesion numbers within 13 weeks time first evaluation pmid33717501 pmcpmc7925953 doi101177 2055217321990852,1.0
wnt effector tcf7l2 promotes oligodendroglial differentiation repressing autocrine bmp4mediated signaling promoting oligodendrocyte ol differentiation represents promising option remyelination therapy treating demyelinating disease multiple sclerosis ms wnt effector transcription factor 7like 2 tcf7l2 upregulated ms lesions proposed inhibit ol differentiation recent data suggest opposite yet underlying mechanisms remain elusive unravel previously unappreciated function tcf7l2 controlling autocrine bone morphogenetic protein bmp 4mediated signaling disrupting tcf7l2 mice sexes results oligodendroglialspecific bmp4 upregulation canonical bmp4 signaling activation vivo mechanistically tcf7l2 binds bmp4 gene regulatory element directly represses transcriptional activity functionally enforced tcf7l2 expression promotes ol differentiation reducing autocrine bmp4 secretion dampening bmp4 signaling importantly compound genetic disruption demonstrates oligodendroglialspecific bmp4 deletion rescues arrested ol differentiation elicited tcf7l2 disruption vivo collectively study reveals novel connection tcf7l2 bmp4 oligodendroglial lineage provides new insights augmenting tcf7l2 promoting remyelination demyelinating disorders mssignificance statement incomplete failed myelin repairs primarily resulting arrested differentiation myelinforming oligodendrocytes ols oligodendroglial progenitor cells one major reasons neurologic progression people affected multiple sclerosis ms using vitro culture systems vivo animal models study unraveled previously unrecognized autocrine regulation bone morphogenetic protein bmp 4mediated signaling wnt effector transcription factor 7like 2 tcf7l2 showed first time tcf7l2 promotes oligodendroglial differentiation repressing bmp4mediated activity dysregulated ms lesions study suggests elevating tcf7l2 expression may possible overcoming arrested oligodendroglial differentiation observed ms patients,1.0
predictors adherence among patients multiple sclerosis using betaconnect autoinjector prospective observational cohort study front neurol 2021 feb 24 12643126 doi 103389 fneur2021643126 ecollection 2021abstractbackground patients multiple sclerosis ms nonadherence diseasemodifying drug therapy associated increased rate ms relapses early identification patients risk nonadherence allow provision timely individualized support aim betapredict study investigate potential predictors adherence patients ms germany treated interferon 1b ifn1b using betaconnect autoinjector methods betapredict national multicenter prospective noninterventional singlearm 24month cohort study patients relapsingremitting ms clinically isolated syndrome receiving ifn1b via betaconnect autoinjector clinicaltrialsgov nct02486640 injection data captured autoinjector primary objective determine baseline predictors compliance persistence adherence ifn1b treatment 12 24 months using multivariableadjusted regression secondary objectives included evaluation satisfaction autoinjector injection site pain vitamin nutrient supplementation clinical course patientrelated outcome measures results 165 patients enrolled 153 available analysis 120 autoinjector data seventytwo patients left study prematurely compliance n 120 persistence n 153 adherence n 120 24 months 891 536 417 respectively compliance 12 24 months predicted intake vitamin d supplements absence specific injection site reactions positive predictors persistence included age 12 24 months previous duration treatment 12 months intake vitamins nutrients vitamin d negative predictor 12 months positive predictors adherence 24 months age experienced ifn1b higher scores specific sf36 subscales positive predictors medicationtaking behavior 24 months satisfaction autoinjector high baseline 24 months median score 9 10 conclusions compliance ifn1b treatment among participants still observation remained high 24month period persistence adherence continuously declined multiple factors affected medicationtaking behavior including patient characteristics treatment history injection site reactions patients perception health support programs importance factors may differ among patients according individual situationpmid33716945 pmcpmc7943887 doi103389 fneur2021643126,0.0
quality life multiple sclerosis differential impact motor cognitive fatigue mult scler j exp transl clin 2021 feb 24 7 1 2055217321996040 doi 101177 2055217321996040 ecollection 2021 janmarabstractbackground multiple sclerosis chronic disease leading reduced quality lifeobjectives investigate whether motor cognitive fatigue impact differently aspects quality life among patients multiple sclerosis independently bodily disabilitymethods 79 patients multiple sclerosis aalborg university hospital denmark included observational crosssectional study subject completed two separate questionnaires regarding fatigue fatigue scale motor cognitive functions modified fatigue impact scale one regarding quality life short form 36 disability measured expanded disability status scale edss scores obtained patient recordsresults fatigue scores significantly correlated areas quality life p 0 05 remained significant adjustment age disease duration edssscore looking type fatigue separately cognitive fatigue correlated mainly mental health aspects quality life motor fatigue physical health areas quality lifeconclusion increased motor cognitive fatigue lead differential reduction physical mental quality life independently bodily disability underlines importance proper assessment treatment fatigue among patients multiple sclerosispmid33708414 pmcpmc7907948 doi101177 2055217321996040,0.0
epigallocatechin gallate progressive ms randomized placebocontrolled trial neurol neuroimmunol neuroinflamm 2021 feb 23 8 3 e964 doi 101212 nxi0000000000000964 print 2021 mayabstractobjective examine whether treatment epigallocatechin gallate egcg influences progression brain atrophy reduces clinical radiologic disease activity markers safe patients progressive multiple sclerosis pms methods enrolled 61 patients primary secondary pms randomized doubleblind parallelgroup phase ii trial oral egcg 1 200 mg daily placebo 36 months optional openlabel egcg treatment extension oe 12month duration primary end point rate brain atrophy quantified brain parenchymal fraction bpf secondary end points radiologic clinical disease parameters safety assessmentsresults cohort 30 patients randomized egcg treatment 31 placebo thirtyeight patients 19 group completed study primary endpoint met 36 months rate decrease bpf 00092 00152 treatment group 00078 00159 placebotreated patients none secondary mri clinical end points revealed group differences adverse events egcg mostly mild occurred similar incidence placebo group one patient egcg group stop treatment due elevated aminotransferases 35 times normal limit conclusions phase ii trial including patients multiple sclerosis ms progressive disease course unable demonstrate treatment effect egcg primary secondary radiologic clinical disease parameters confirming overall beneficial safety profileclinicaltrialgov identifier nct00799890classification evidence phase ii trial provides class ii evidence patients pms egcg safe well tolerated significantly reduce rate brain atrophypmid33622766 doi101212 nxi0000000000000964,0.0
inflammaging markers characteristic advanced age show similar levels frailty dependency sci rep 2021 feb 23 11 1 4358 doi 101038 s41598021839917abstractthe improvement life quality medical advances resulted increased life expectancy despite health status commonly worsens last years life frailty intermediate reversible state often precedes dependency therefore identification may essential prevent dependency however consensus best tools identify frailty sense diverse molecules proposed potential biomarkers investigations pointed increased chronic inflammation inflammaging frailty others report differences work evaluated circulating concentration inflammaging markers adults older adults aged 70 years elisa luminex techniques barthel index applied evaluation dependency timed upandgo gait speed short physical performance battery tilburg frailty indicator gerontopole frailty screening tool used identification frailty crp tnf il6 albumin concentrations measured found elevated inflammation present older adults differences frailty dependency reported results consistent evaluated frailty scales highlighting need reconsider increased inflammation biomarker frailtypmid33623057 doi101038 s41598021839917,0.0
combined therapy a1ar agonists a2aar antagonists neuroinflammation molecules 2021 feb 23 26 4 1188 doi 103390 molecules26041188abstractalzheimers parkinsons multiple sclerosis neurodegenerative diseases related neuronal degeneration death specific areas central nervous system pathologies associated neuroinflammation involved disease progression halting process represents potential therapeutic strategy evidence suggests microglia function regulated a1 a2a adenosine receptors ar considered neuroprotective neurodegenerative receptors respectively manuscripts aim elucidate role receptors neuroinflammation modulation potent selective a1ar agonists n6cyclopentyl2 3deoxyadenosine substituted unsubstituted 2 position a2aar antagonists 9ethyladenine substituted 8 2 position synthesized house using n13 microglial cells addition combined therapy a1ar agonists a2aar antagonists modulate neuroinflammation evaluated results showed a1ar agonists able varying degrees prevent inflammatory effect induced cytokine cocktail tumor necrosis factor tnf interleukin il 1 interferon ifn a2aar antagonists showed good ability counteract neuroinflammation moreover effect achieved combining two effective compounds 1 6 doses previously found noneffective greater treatment effect two compounds used separately maximal dosepmid33672225 doi103390 molecules26041188,1.0
diagnosis treatment multiple sclerosis review jama 2021 feb 23 325 8 765779 doi 101001 jama202026858abstractimportance multiple sclerosis ms autoimmunemediated neurodegenerative disease central nervous system characterized inflammatory demyelination axonal transection ms affects estimated 900 000 people us ms typically presents young adults mean age onset 2030 years can lead physical disability cognitive impairment decreased quality life review summarizes current evidence regarding diagnosis treatment msobservations ms typically presents young adults aged 20 30 years unilateral optic neuritis partial myelitis sensory disturbances brainstem syndromes internuclear ophthalmoplegia developing several days prevalence ms worldwide ranges 5 300 per 100 000 people increases higher latitudes overall life expectancy less general population 759 vs 834 years ms commonly affects women female male sex distribution nearly 31 diagnosis made based combination signs symptoms radiographic findings eg magnetic resonance imaging mri t2 lesions laboratory findings eg cerebrospinal fluidspecific oligoclonal bands components 2017 mcdonald criteria nine classes diseasemodifying therapies dmts varying mechanisms action routes administration available relapsingremitting ms defined relapses onset stable neurologic disability episodes secondary progressive ms activity defined steadily increasing neurologic disability following relapsing course evidence ongoing inflammatory activity drugs include interferons glatiramer acetate teriflunomide sphingosine 1phosphate receptor modulators fumarates cladribine 3 types monoclonal antibodies one additional dmt ocrelizumab approved primary progressive ms dmts reduce clinical relapses mri lesions new t2 lesions gadoliniumenhancing lesions efficacy rates current dmts defined reduction annualized relapse rates compared placebo active comparators range 2968 adverse effects include infections bradycardia heart blocks macular edema infusion reactions injectionsite reactions secondary autoimmune adverse effects autoimmune thyroid diseaseconclusions relevance ms characterized physical disability cognitive impairment symptoms affect quality life treatment dmt can reduce annual relapse rate 29 68 compared placebo active comparatorpmid33620411 doi101001 jama202026858,1.0
1 000th transplant multiple sclerosis autoimmune disorders hsctmexico program myriad experiences knowledge front neurol 2021 feb 22 12647425 doi 103389 fneur2021647425 ecollection 2021abstractafter gaining experience conducting auto allografts persons hematological diseases hsct programs puebla monterrey mxico study outlines subsequent program autografting patients autoimmune conditions first transplant multiple sclerosis conducted puebla july 5 2006 2015 increased activity autografting persons autoimmune conditions two campuses hsctmxico program puebla monterrey december 6 2020 patient number 1 000 program autografted experience significant reduction expanded disability status scale score achieved three phenotypes disease median 51 45 points whereas response rate defined decrease least 05 edss score regardless baseline edss unchanged edss 83 78 73 12 months relapsingremitting primaryprogressive secondaryprogressive forms multiple sclerosis respectively addition analyzing viability safety efficacy method study contributes new knowledge field stem cell transplantation multiple sclerosispmid33692748 pmcpmc7937693 doi103389 fneur2021647425,0.0
insights fostering resilience young adults multiple sclerosis aftermath covid19 emergency italian survey front psychiatry 2021 feb 22 11588275 doi 103389 fpsyt2020588275 ecollection 2020abstractobjective recent evidence demonstrated covid19 pandemic taking toll mental health general population psychological consequences might even severe patients special healthcare needs psychological vulnerabilities due chronic diseases multiple sclerosis ms thus aimed explore psychological impact pandemic subsequent healthcare service changes young adults ms living italy examine coping strategies preferences regarding psychological support aftermath pandemic methods data collected using crosssectional webbased survey advertised social networks report quantitative descriptive statistics ttests oneway anova qualitative data inductive content analysis results two hundred fortyseven respondents mean age 32 7 years mainly relapsingremitting ms italian regions participated participants felt worried confused sad vulnerable disease pandemic comparison selfevaluation period covid19 outbreak similarly perception control ms decreased pandemic comparison retrospective evaluation period covid19 outbreak p 001 canceled postponed visits exams listed frequent ms management changes modified postponed pharmacological treatment representing stressful change psychological support dealing pandemicrelated fears improving ms acceptance wellbeing considered extremely important almost 40 respondents different coping strategies mentioned qualitative section survey social support hobbies keeping busy frequent ones conclusions considering enormous impact pandemic young adults ms urge ms clinical centers implement psychological support programs address potentially longlasting psychological negative impact thus fostering therapeutic alliance threatened infection prevention measures imposed pandemic promoting psychological resources adaptively managing future waves covid19pmid33692703 pmcpmc7938709 doi103389 fpsyt2020588275,0.0
cuprizoneinduced neurotoxicity human neural cell lines mediated reversible mitochondrial dysfunction relevance demyelination models brain sci 2021 feb 22 11 2 272 doi 103390 brainsci11020272abstractsuitable vivo vitro models instrumental development new drugs aimed improving symptoms progression multiple sclerosis ms cuprizone cpz induced murine model gained momentum recent decades aiming address demyelination component disease work aims assessing differential cytotoxicity cpz cells different types different species human oligodendroglial hog human neuroblastoma shsy5y human glioblastoma t98 mouse microglial n9 cell lines moreover effect cpz investigated primary rat brain cells cell viability assayed oxygen rate consumption 3 4 5dimethylthiazol2yl 2 5diphenyltetrazolium bromidebased mtt method results demonstrated cpz cause death assayed cell models affected mitochondrial function aerobic cell respiration thus compromising cell metabolism neural cells neuronglia cocultures sense found differential vulnerability glial cells neurons case cpzinduced mouse model ms addition findings demonstrated reduced viability spontaneous reverted timedependent manner treatment discontinuation reversible cellbased model may help investigate role mitochondria disease study molecular intricacies underlying pathophysiology ms demyelinating diseasespmid33671675 doi103390 brainsci11020272,1.0
pharmacological management neurogenic bowel dysfunction spinal cord injury multiple sclerosis systematic review clinical implications j clin med 2021 feb 22 10 4 882 doi 103390 jcm10040882abstractneurogenic bowel dysfunction nbd common problem people spinal cord injury sci multiple sclerosis ms seriously impacts quality life pharmacological management important component conservative bowel management objective study first assemble list pharmacological agents medications medicated suppositories used current practice second systematically examined current literature pharmacological agents manage neurogenic bowel dysfunction individuals specifically sci ms searched medline embase cinahl databases june 2020 used grade system provide systematic approach evaluating evidence twentyeight studies included review found stark discrepancy large number agents currently prescribed limited amount literature small amount literature sci little literature available ms lowquality evidence supporting rectal medications key component conservative bowel care sci based findings literature clinical experience authors provided clinical insights proposed treatments medications form three case study examples patients sci mspmid33671492 doi103390 jcm10040882,0.0
integration il2 il4 signals coordinates divergent regulatory t cell responses drives therapeutic efficacy elife 2021 feb 22 10e57417 doi 107554 elife57417abstractcells exist within complex milieus communicating factors cytokines combine generate contextspecific responses yet nearly knowledge function cytokine signaling propagated downstream recognition based response individual cytokines found regulatory t cells tregs integrate concurrent signaling initiated il2 il4 generate response divergent sum two pathways isolation il4 stimulation stat6 phosphorylation blocked il2 il2 il4 synergized enhance stat5 phosphorylation il10 production selective proliferation il10producing tregs leading increased inhibition conventional t cell activation reversal asthma multiple sclerosis mice data define mechanism combinatorial cytokine signaling lay foundation upon better understand origins cytokine pleiotropy informing improved clinical use cytokinespmid33617447 doi107554 elife57417,0.0
assessment recent evidence management patients systemic sclerosisassociated interstitial lung disease systematic review erj open res 2021 feb 22 7 1 002352020 doi 101183 23120541002352020 ecollection 2021 janabstractthis systematic review summarises current evidence help guide treatment decisions patients systemic sclerosis ssc associated interstitial lung disease ild systematic search literature january 2012 april 2018 including grey literature searched 1992 2011 conducted using multiple electronic databases guidelines metaanalyses randomised controlled trials observational studies reporting risk stratification screening diagnosis treatment management outcomes patients sscild included quality assessment included evidence undertaken total 2464 publications identified 280 included multiple independent risk factors ild patients ssc identified including older age male sex baseline pulmonary function highresolution computed tomography hrct used characterising ild patients ssc pulmonary function tests key adjunctive component diagnostic monitoring pathway clinical value biomarkers relating sscild diagnosis assessment disease progression unknown present immunosuppressive therapy monotherapy combined therapy current standard care sscild longterm evidence effective safe treatment sscild limited identification patients risk sscild remains challenging hrct pulmonary function tests key diagnosing monitoring disease progression although immunosuppressive therapy considered current firstline treatment partly associated adverse effects longterm followup evidence limited novel therapies biomarkers explored wellcontrolled clinical studiespmid33644224 pmcpmc7897846 doi101183 23120541002352020,0.0
increased expression ephrins immune cells patients relapsing remitting multiple sclerosis affects oligodendrocyte differentiation int j mol sci 2021 feb 22 22 4 2182 doi 103390 ijms22042182abstractthe effect inflammatory response regenerative processes brain complex complexity even greater cause tissue damage autoimmune response multiple sclerosis ms immunemediated disease demyelination foci formed central nervous system degree repair oligodendrocyte regeneration remyelination insufficient ephrins membranebound ligands activating tyrosine kinase signaling proteins known inhibitory effect oligodendrocyte regeneration study examined expression ephrins immune cells 43 patients relapsingremitting rr ms compared 27 matched healthy controls hc found increased expression ephrina2 a3 b3 especially t cell subpopulations also showed overexpression ephrins immune cells patients rrms increases forward signaling pathway expression ephrins immune cells inhibitory effect differentiation oligodendrocyte precursor cells opcs vitro study findings support concept immune activity t cells patients rrms inhibitory effect differentiation capacity opcs expression forward signaling ephrinspmid33671716 doi103390 ijms22042182,1.0
role il23 il17 pathway rheumatic diseases overview front immunol 2021 feb 22 12637829 doi 103389 fimmu2021637829 ecollection 2021abstractinterleukin23 il23 proinflammatory cytokine composed two subunits il23a p19 il12 23b p40 latter shared interleukin12 il12 il23 mainly produced macrophages dendritic cells response exogenous endogenous signals drives differentiation activation t helper 17 th17 cells subsequent production il17a il17f il6 il22 tumor necrosis factor tnf although il23 plays pivotal role protective immune response bacterial fungal infections dysregulation shown exacerbate chronic immunemediated inflammation wellestablished experimental data support concept il23 il17 axis activation contributes development several inflammatory diseases psa psoriasis psoriatic arthritis ankylosing spondylitis ibd inflammatory bowel disease ra rheumatoid arthritis ss sjogren syndrome ms multiple sclerosis result emerging clinical studies focused blockade pathogenic axis promising therapeutic target several autoimmune disorders nevertheless greater understanding contribution still requires investigation review aims elucidate recent studies literature data pathogenetic role il23 th17 cells inflammatory rheumatic diseasespmid33692806 pmcpmc7937623 doi103389 fimmu2021637829,0.0
risk psychiatric disorders multiple sclerosis nationwide cohort study asian population neuropsychiatr dis treat 2021 feb 22 17587604 doi 102147 ndts268360 ecollection 2021abstractbackground multiple sclerosis ms demyelinating disease can damage neurons brain spinal cord associated several psychiatric disorders however studies evaluated risk psychiatric disorders patients ms using nationwide database study investigated association ms risk psychiatric disordersmethods using data taiwan national health insurance research database 2000 2015 identified 1066 patients ms adjustment confounding factors fine grays competing risk model used compare risk psychiatric disorders 15 years followupresults patients ms 531 462286 per 105 person years developed psychiatric disorders contrast 891 3198 controls 248531 per 105 person years developed psychiatric disorders fine grays competing risk model revealed adjusted hazard ratio hr 5044 95 confidence interval 44485870 p 0001 adjustment covariates ms associated depression anxiety bipolar disorder sleep disorders schizophrenia schizophreniform disorder psychotic disorders adjusted hr 12464 4650 6987 9103 2552 2600 2441 2574 respectively p 0001 diseasemodifying drugs associated lower risk anxiety depressionconclusion patients ms determined higher risk developing wide range psychiatric disorderspmid33654401 pmcpmc7910105 doi102147 ndts268360,1.0
early treatment initiation oral prednisolone relapse prevention alleviates depression fatigue aquaporin4positive neuromyelitis optica spectrum disorder front neurol 2021 feb 22 12608149 doi 103389 fneur2021608149 ecollection 2021abstractbackground neuromyelitis optica spectrum disorder nmosd relapsing autoimmunerelated neurological disorder central nervous system patients nmosd serum antiaquaporin4 immunoglobulin g antibodies aqp4igg addition optic neuritis myelitis insidious symptoms depressive state chronic fatigue nmosd gradually recognized methods elucidate impact low mediumdose oral prednisolone psl relapse prevention therapy psychiatric disturbances chronic fatigue nmosd evaluated clinical data 39 patients aqp4iggpositive nmosd along details present cumulative oral psl dosage results thirtysix 39 patients treated low mediumdose oral psl mean standard deviation present daily dose oral psl 79 40 mg day none patients treated daily psl dose 15 mg result disease duration untreated period starting oral psl showed weak moderate correlations subsequent severities psychiatric disturbance fatigue level meanwhile none treatmentrelated variables evaluated present oral psl daily dose cumulative psl dose months oral psl administration previous courses steroid pulse therapy coadministered immunosuppressants correlated insidious symptoms conclusion results suggest use longterm low mediumdose oral psl 15 mg daily relapse prevention aqp4iggpositive nmosd aggravate psychiatric fatigue conditions contrary early initiation oral psl relapse prevention together significantly decreased relapse rate alleviated subsequent depressive state fatigue diseasepmid33692739 pmcpmc7938311 doi103389 fneur2021608149,0.0
dimethyl fumarate induces metabolic crisie suppress pancreatic carcinoma front pharmacol 2021 feb 22 12617714 doi 103389 fphar2021617714 ecollection 2021abstractdimethyl fumarate dmf approved drug used treatment multiple sclerosis ms psoriasis therapy multiple studies demonstrated pharmacological activities dmf anticancer agent particular studies shown dmf can modulate nrf2 ho1 nqo1 antioxidant signal pathway inactivate nfb suppress growth colon breast cancer cells induce cell death study aimed evaluate antitumor activities dmf pancreatic cancer pc focusing cell death predominant mechanism response showed mitochondrial respiration aerobic glycolysis severely depressed following treatment dmf effects abrogated treatment lcysteine nacetyllcysteine nac importantly verified dmf induced metabolic crisis cell death related alterations ros data implied mthfd1 potential downstream target dmf identified molecular docking analysis finally confirmed mthfd1 upregulated pc overexpression mthfd1 negatively related outcomes pc patients data indicate dmf induces metabolic crisie suppress cell growth potential novel therapy treatment pcpmid33692690 pmcpmc7937954 doi103389 fphar2021617714,0.0
act10041239 firstinclass cxcr7 antagonist immunomodulatory promyelinating effects treatment inflammatory demyelinating diseases pubmed current strategies treatment demyelinating diseases multiple sclerosis ms based antiinflammatory immunomodulatory drugs drugs potential reduce frequency new lesions directly promote remyelination damaged central nervous system cns targeting cxcr7 ackr3 postulated potential therapeutic approach demyelinating diseases leading immunomodulation reducing leukocyte infiltrates promyelination enhancing myelin repair act10041239 potent selective insurmountable orally available firstinclass cxcr7 receptor antagonist effect act10041239 evaluated myelin oligodendrocyte glycoprotein mog induced experimental autoimmune encephalomyelitis eae cuprizoneinduced demyelination mouse models addition act10041239 assessed rat oligodendrocyte precursor cell opc differentiation assay vitro moginduced eae model act10041239 treatment 10100 mg kg twice daily orally showed significant dosedependent reduction disease clinical scores resulting increased survival highest dose tested 100 mg kg twice daily act10041239 delayed disease onset significantly reduced immune cell infiltrates cns plasma neurofilament light chain concentration treatment act10041239 dosedependently increased plasma cxcl12 concentration correlated reduction cumulative disease score furthermore cuprizone model act10041239 treatment significantly increased number mature myelinating oligodendrocytes enhanced myelination vivo vitro act10041239 promoted maturation opcs myelinating oligodendrocytes results provide evidence act10041239 reduces neuroinflammation enhances myelin repair substantiating rationale explore therapeutic potential clinical setting,1.0
tissue plasminogen activator worsens experimental autoimmune encephalomyelitis complementary actions lymphoid myeloid cell responses j neuroinflammation 2021 feb 20 18 1 52 doi 101186 s12974021021025abstractbackground tissue plasminogen activator tpa serine protease involved fibrinolysis released endothelial cells also expressed neurons glial cells central nervous system cns interestingly enzyme also contributes pathological processes cns neuroinflammation activating microglia increasing bloodbrain barrier permeability nevertheless role control adaptive innate immune response remains poorly understoodmethods tpa effects myeloid lymphoid cell response studied vivo mouse model multiple sclerosis experimental autoimmune encephalomyelitis vitro splenocytesresults tpa animals exhibited less severe experimental autoimmune encephalomyelitis wildtype counterparts accompanied reduction lymphoid myeloid cell populations spinal cord parenchyma parallel tpa increased t cell activation proliferation well cytokine production proteasedependent mechanism via plasmin generation addition tpa directly raised expression mhcii costimulatory molecules cd80 cd86 surface dendritic cells macrophages direct action dependent activation epidermal growth factor receptorconclusions study provides new insights mechanisms responsible harmful functions tpa multiple sclerosis animal models tpa promotes proliferation activation lymphoid myeloid populations distinct though complementary mechanismspmid33610187 doi101186 s12974021021025,0.0
assessment disability progression independent relapse brain mri activity patients multiple sclerosis poland j clin med 2021 feb 19 10 4 868 doi 103390 jcm10040868abstractthe aim study verify association clinical relapses brain activity disability progression relapsing remitting multiple sclerosis patients receiving diseasemodifying treatments poland disability progression defined relapseassociated worsening raw progression independent relapse activity pira progression independent relapses brain mri activity pirma data therapeutic program monitoring system analyzed three panels patients identified r0 relapse treatment r1 r2 occurrence relapse first second year treatment respectively r0 panel detected 46 pira patients 24 months p 0001 50 36 months 56 48 months 61 60 months restricting panel patients without brain mri activity detected 30 pirma patients 12 months 45 24 months varying 53 62 36 60 months treatment respectively r1 panel raw detected 156 patients 12 months absence relapses 97 24 months 68 36 months treatment r2 group associated raw significantly frequently 24 months compared r1 12 months 207 p 005 without statistical difference later work confirmed disability progression independent relapses brain mri activitypmid33669799 doi103390 jcm10040868,0.0
magnetic resonance imaging multiple sclerosis 70 tesla j vis exp 2021 feb 19 168 doi 103791 62142abstractthe overall goal article demonstrate stateoftheart ultrahigh field uhf magnetic resonance mr protocol brain 70 tesla multiple sclerosis ms patients ms chronic inflammatory demyelinating neurodegenerative disease characterized white gray matter lesions detection spatially temporally disseminated t2hyperintense lesions use mri 15 t 3 t represents crucial diagnostic tool clinical practice establish accurate diagnosis ms based current version 2017 mcdonald criteria however differentiation ms lesions brain white matter lesions origins can sometimes challenging due resembling morphology lower magnetic field strengths typically 3 t ultrahigh field mr uhfmr benefits increased signaltonoise ratio enhanced spatial resolution key superior imaging accurate definitive diagnoses subtle lesions hence mri 70 t shown encouraging results overcome challenges ms differential diagnosis providing msspecific neuroimaging markers eg central vein sign hypointense rim structures differentiation ms grey matter lesions markers others can identified mr contrasts t1 t2 t2 phase diffusion substantially improve differentiation ms lesions occurring neuroinflammatory conditions neuromyelitis optica susac syndrome article describe current technical approach study cerebral white grey matter lesions ms patients 70 t using different mr acquisition methods uptodate protocol includes preparation mr setup including radiofrequency coils customized uhfmr standardized screening safety interview procedures ms patients patient positioning mr scanner acquisition dedicated brain scans tailored examining mspmid33682856 doi103791 62142,1.0
platelets multiple sclerosis early central mediators inflammation neurodegeneration attractive targets molecular imaging sitedirected therapy front immunol 2021 feb 19 12620963 doi 103389 fimmu2021620963 ecollection 2021abstractplatelets clearly central thrombosis hemostasis addition recently evidence emerged nonhemostatic roles platelets including inflammatory immune reactions responses platelets express immunologically relevant ligands receptors demonstrate adhesive interactions endothelial cells monocytes neutrophils tolllike receptor tlr mediated responses properties make platelets central innate adaptive immunity potential candidate key mediators autoimmune disorders multiple sclerosis ms common chronic autoimmune central nervous system cns disease association platelets ms first indicated increased adhesion platelets endothelial cells followed reports identifying structural functional changes platelets chronic activation peripheral blood ms patients platelet presence ms lesions recent revelation structural functional abnormalities associated ms forms stages investigations based murine experimental autoimmune encephalomyelitis eae ms model first revealed contribution eae pathogenesis exacerbation cns inflammation early role platelets eae development via plateletneuron plateletastrocyte associations sialated gangliosides lipid rafts studies refined extended findings identifying critical timing platelet accumulation preclinical eae establishing initiating central rather merely exacerbating role platelets disease development furthermore demonstrated plateletneuron associations eae coincident behavioral changes preceding earliest detectable autoreactive t cell accumulation combination findings establish new paradigm asserting platelets play neurodegenerative well neuroinflammatory role ms therefore two pathological processes causally linked review will discuss implications findings understanding ms future applications imaging toward early detection ms novel strategies platelettargeted treatment mspmid33679764 pmcpmc7933211 doi103389 fimmu2021620963,0.0
antigenspecific treatment modalities ms past present future front immunol 2021 feb 19 12624685 doi 103389 fimmu2021624685 ecollection 2021abstractantigenspecific therapy multiple sclerosis may lead effective therapy induction tolerance wide range myelinderived antigens without hampering normal surveillance effector function immune system numerous attempts restore tolerance toward myelinderived antigens made past decades animal models multiple sclerosis clinical trials multiple sclerosis patients review will give overview current approaches antigenspecific therapy clinical development multiple sclerosis well provide insight challenges future antigenspecific treatment strategies multiple sclerosispmid33679769 pmcpmc7933447 doi103389 fimmu2021624685,1.0
common peripheral immunity mechanisms multiple sclerosis alzheimer#39 s disease front immunol 2021 feb 19 12639369 doi 103389 fimmu2021639369 ecollection 2021abstractneurodegenerative diseases closely related inflammatory autoimmune events suggesting dysregulation immune system key pathological factor multiple sclerosis ms alzheimers disease ad characterized infiltrating immune cells activated microglia astrocyte proliferation neuronal damage moreover ms ad share common proinflammatory signature characterized peripheral leukocyte activation transmigration central nervous system cns ms ad characterized accumulation activated neutrophils blood leading progressive impairment bloodbrain barrier migrated cns early phases ms ad neutrophils promote local inflammation contributes pathogenesis clinical progression role circulating t cells ms wellestablished whereas contribution adaptive immunity ad pathogenesis progression recent discovery even blocking transmigration t cells cns can benefit ms ad patients suggesting common adaptive immunity mechanisms play detrimental role disease also growing evidence regulatory t cells beneficial initial stages ms ad supporting link modulatory immune compartments neurodegenerative disorders number resting regulatory t cells declines diseases indicating common pathogenic mechanism involving dysregulation cells although precise role control neuroinflammation remains unclear modulation leukocyte functions can benefit ms patients insight role peripheral immune cells may reveal new targets pharmacological intervention neuroinflammatory neurodegenerative diseases including adpmid33679799 pmcpmc7933037 doi103389 fimmu2021639369,0.0
lactobacillus acidipiscis induced regulatory gamma delta t cells attenuated experimental autoimmune encephalomyelitis front immunol 2021 feb 19 12623451 doi 103389 fimmu2021623451 ecollection 2021abstractmultiple sclerosis chronic autoimmune disease involving central nervous system shows high disability rate pathogenesis complicated good treatment recent years indepth studies regulation gastrointestinal flora relationship mammalian immune system intestinal flora extensively explored changes composition structure gastrointestinal flora can affect characteristics development host immune system even induce series central nervous system inflammation events occurrence development multiple sclerosis closely related continuous destruction intestinal barrier caused intestinal dysbacteriosis study analyzed lactobacillus acidipiscis mouse model experimental autoimmune encephalomyelitis eae found amount l acidipiscis intestinal tract inversely proportional progress eae development addition number cd4+ foxp3+ regulatory t cells mesenteric lymph nodes mice increased significantly mice fed l acidipiscis differentiation cd4+ t cells th1 th17 cells inhibited however protective effect l acidipiscis lost t celldeficient mice hence concluded depend presence regulatory t cells intestinal epithelium moreover including l acidipiscis enhanced development v1+ t cells suppressed v4+ t cells summary results demonstrated ability l acidipiscis induce generation regulatory t cells suppress development encephalomyelitic th1 th17 cells progress eaepmid33679767 pmcpmc7933195 doi103389 fimmu2021623451,0.0
multilayer analysis quantitative 7t magnetic resonance imaging cortex multiple sclerosis patients reveals pathology associated disability abstractbackgroundcortical demyelination relevant aspect tissue damage multiple sclerosis ms microstructural changes may affect layer cortex differentlyobjectivesto evaluate sensitivity quantitative magnetic resonance imaging qmri measurements cortical layers clinically accessible biomarkers grey matter gm pathologymethodsfortyfive participants ms underwent 7t magnetic resonance imaging mri brain magnetization prepared two rapid acquisition gradient echoes mp2rage processed t1weighted images t1 map multiecho gradient echo images processed quantitative susceptibility r2 maps cortical gm volumes segmented four cortical layers relaxometry metrics calculated within layersresultssignificant correlations found disability scales multilayer metrics example expanded disability status scale edss peak height ph subpial t1 0372 p0050 inner r2 0359 p0050 cortical layers multivariate regression showed interdependency atrophy cortical metrics instances independent relationship cortical metrics disability othersconclusioncortical layer 7t qmri analyses reveal layerspecific relationships disability ms allow emergence clinically relevant associations hidden analysing full cortex,1.0
crisprmediated rapid generation neural cellspecific knockout mice facilitates research neurophysiology pathology mol ther methods clin dev 2021 feb 18 20755764 doi 101016 jomtm202102012 ecollection 2021 mar 12abstractinducible conditional knockout mice important tools studying gene function disease therapy generation costly timeconsuming introduced clustered regularly interspaced short palindromic repeats crispr cre lslcas9 transgenecarrying mouse line using adenoassociated virus aav phpeb rapidly knockout gene s specifically central nervous system cns cells adult mice neun neurons gfap astrocytes knocked 2 weeks intravenous injection vector efficiency comparable inducible creloxp conditional knockout functional testing generated astrocytespecific act1 knockout mice exhibited phenotype similar mice creloxpmediated act1 knockout animal model multiple sclerosis ms autoimmune disorder cns novel technique neural cellspecific knockout can induced rapidly weeks costeffectively study provides new approach building inducible conditional knockout mice greatly facilitate research cns biology diseasepmid33738329 pmcpmc7940702 doi101016 jomtm202102012,0.0
man erythematosquamous plaques ned tijdschr geneeskd 2021 feb 18 165d5795abstracta 43yearold male visited dermatology department skin eruption diagnosed psoriasis began 1 month starting peginterferon1a therapy multiple sclerosis peginterferon known able induce psoriasis well medication pathophysiology remains unclearpmid33651510,0.0
diagnosis multiple sclerosis following whiplash injury true association cureus 2021 feb 18 13 2 e13411 doi 107759 cureus13411abstractwe report case previously well 25yearold caucasian female whose diagnosis multiple sclerosis ms followed significant trauma symptoms signs developed quickly satisfied criteria rapidly evolving relapsingremitting ms started natalizumab tysabri stabilized discuss existing literature traumatic demyelination possible underlying mechanismspmid33758706 pmcpmc7980313 doi107759 cureus13411,1.0
csf proteome multiple sclerosis subtypes related brain lesion transcriptomes sci rep 2021 feb 18 11 1 4132 doi 101038 s41598021835915abstractto identify markers csf multiple sclerosis ms subtypes used twostep proteomic approach discovery proteomics compared 169 pooled csf ms subtypes inflammatory degenerative cns diseases nmo spectrum alzheimer disease healthy controls ii next 299 proteins selected comprehensive statistics quantified 170 individual csf samples iii genes identified proteins also screened among transcripts 73 ms brain lesions compared 25 control brains ftest based feature selection resulted 8 proteins differentiating ms subtypes secondary progressive sp ms different also controls genes 7 8 proteins present ms brain lesions golm significantly differentially expressed active chronic active inactive remyelinating lesions frzb active chronic active lesions selenbp1 inactive lesions volcano maps normalized proteins different disease groups also indicated highest amount altered proteins spms apolipoprotein ci apolipoprotein aii augurin receptortype tyrosineprotein phosphatase gamma trypsin1 upregulated csf ms subtypes compared controls csf profile associated brain lesion spectrum highlight noninflammatory mechanisms differentiating cns diseases ms subtypes uniqueness spmspmid33603109 doi101038 s41598021835915,1.0
modeling healthy anatomy artificial intelligence unsupervised anomaly detection brain mri radiol artif intell 2021 feb 17 3 3 e190169 doi 101148 ryai2021190169 ecollection 2021 mayabstractpurpose develop unsupervised deep learning model mr images normal brain anatomy automatically detect deviations indicative pathologic states abnormal mr imagesmaterials methods retrospective study spatial autoencoders skipconnections can learn compress reconstruct data leveraged learn normal variability brain mr scans healthy individuals total 100 normal inhouse mr scans used training subsequently model unable reconstruct anomalies well characteristic exploited detecting delineating various diseases computing difference input data reconstruction unsupervised model compared supervised unet thresholdbased classifier trained data 50 patients multiple sclerosis inhouse dataset 50 patients cancer imaging archive unsupervised supervised unet models tested five different datasets containing mr images microangiopathy glioblastoma multiple sclerosis precisionrecall statistics derivations thereof mean area precisionrecall curve dice score used quantify lesion detection segmentation performanceresults unsupervised approach outperformed naive thresholding approach lesion detection mean f1 scores ranging 17 62 vs 64 15 across five different datasets performed similarly supervised unet 2064 across variety pathologic conditions outperformance mostly driven improved precision compared thresholding approach mean precisions 1559 vs 3410 model also developed create anomaly heatmap displayconclusion unsupervised deep learning model able automatically detect anomalies brain mr images high performance supplemental material available article keywords brain brain stem computer aided diagnosis cad convolutional neural network cnn experimental investigations head neck mrimaging quantification segmentation stacked autoencoders technology assessment tissue characterization rsna 2021pmid34136814 pmcpmc8204131 doi101148 ryai2021190169,0.0
changes multiple sclerosis symptoms associated changes work productivity people living multiple sclerosis abstractbackgroundwhile employment rates increased people multiple sclerosis pwms little known longitudinal trends work productivityobjectiveto describe longitudinal patterns work productivity examine factors associated annual change work productivity pwmsmethodsstudy participants employed participants australian ms longitudinal study amsls followed 2015 2019 least two repeated measures n 2121 used linear mixed models examine withinindividual variations ms symptoms associated changes work productivityresultsthe mean annual change work productivity 2015 2019 023 sd 1868 actual severity symptoms rather changes severity symptoms associated change work productivity year multivariable model every unit increase mean annual change pain sensory symptoms feelings anxiety depression fatigue cognitive symptoms independently associated 243 155 101 annual reductions work productivity respectivelyconclusionindividual changes work productivity largely driven changes symptom severity rather absolute severity stabilising improving ms symptoms might improve work productivity,0.0
mendelian randomization provides evidence causal role bidirectional relationship depression multiple sclerosis abstractbackgroundmajor depressive disorder mdd common multiple sclerosis ms incidence rises ms diagnosis however causality direction association remain unclearobjectivethe objective investigate bidirectional relationship ms mdd using mendelian randomization mr methodswe selected genetic instruments associated risk mdd n660 937 cases 1 453 489 controls ms n47 429 cases 68 374 controls using twosample mr examined putative causal effects either direction sensitivity analyses assess pleiotropy also adjusted body mass index bmi multivariable mrresultswe found effect genetic liability mdd odds ms or107 doubling odds 95 ci090128 similarly findings support causal effect genetic liability ms mdd or100 doubling odds 95 ci099101 despite heterogeneity sensitivity analyses indicated bias pleiotropy unlikely conversely genetic predisposition toward higher bmi increased odds ms or134 sd increase 95 ci109165 mdd or108 95 ci101115 conclusionthis study support causal association mdd genetic liability ms susceptibility vice versa genetic evidence suggesting commonality obesity conditions may partly explain increased incidence depression prems diagnosis,0.0
personalised inpatient multidisciplinary rehabilitation elicits clinically relevant improvements physical function patients multiple sclerosis danish ms hospitals rehabilitation study mult scler j exp transl clin 2021 feb 17 7 1 2055217321989384 doi 101177 2055217321989384 ecollection 2021 janmarabstractpurpose evidence effects inpatient multidisciplinary rehabilitation mdr physical function patients multiple sclerosis ms limited particularly whether clinically relevant improvements can achieved aim study therefore investigate effects personalised inpatient mdr physical function ms patientsmethods embedded danish ms hospitals rehabilitation study pragmatic study performed ms patients undergoing four weeks inpatient mdr specifically targeting physical function outcomes assessed baseline n 142 discharge n 137 six months followup n 126 using sixminute walk test 6mwt sixspot step test ssst five times sit stand test 5sts ninehole peg test nhpt dynamic gait index dgi 12item ms walking scale msws results baselinetodischarge significant clinically relevant improvements found measures walking capacity 6mwt ssst 5sts dgi msws p 005 along significant clinically relevant improvements upper extremity function nhpt p 005 whilst comparable improvements observed within subgroups ms phenotype relapsingremitting rr vs secondary + primary progressive sp + pp disease severity moderate edss2555 vs severe edss6075 age young middleaged age2459 vs old age6065 attenuated adaptation nevertheless observed 6mwt affected vulnerable subgroups ie sp + pp edss6075 age6065 significant improvements walking capacity upper extremity function persisted six months followup exceed anymore thresholds regarded clinically relevantconclusion results provide novel evidence personalised inpatient mdr targeting physical function ms patients elicits significant clinically relevant improvements physical functionpmid33643662 pmcpmc7894699 doi101177 2055217321989384,1.0
multiple sclerosis iran epidemiological update focus air pollution debate j clin transl res 2021 feb 17 7 1 4960 ecollection 2021 feb 25abstractbackground multiple sclerosis ms common neurologic disorder central nervous system growing incidence prevalence worldwide middle east article aimed find potential relationship ms air pollution iranmethods assessing published articles ms air pollution iran situation ms well air soil pollution iran clarified studies air pollution potential effect iranian ms patients checked 2020results ms prevalence distributed across iran provinces highest rates isfahan located center iran higher rates ms isfahan tehran metropolitan might due industrial pollution cities hypothesis true nonindustrial provinces based published atlas ms iran seems highrisk belt northwest southeastconclusion many risk factors ms iran including age gender vitamin d deficiency smoking air pollution potential main risk factor ms might air pollution considering isfahan tehran provinces however chahar mahal bakhtiary province nonindustrial nature second highest ms rates follow hypothesisrelevance patients finding air pollution main potential risk factor ms big provinces including isfahan tehran effect factor can also considered diagnosis treatmentpmid34104808 pmcpmc8177027,0.0
health economics diseasemodifying therapy multiple sclerosis united states ther adv neurol disord 2021 feb 17 141756286420987031 doi 101177 1756286420987031 ecollection 2021abstractmultiple sclerosis ms chronic neuroinflammatory condition associated significant disability economic burden ms substantial high rising diseasemodifying therapy dmt prices single largest drivers healthcare expenditures much last decade price increases dmts surpassed 10 annually currently many ms dmts exceed us90 000 year economic value widely debated addition creating financial burden healthcare system high dmt costs negatively impact patients unaffordable outofpocket costs excessive restrictions insurance companies objective narrative review summarize economic issues related ms dmts including trends pricing relative value effects patient care united statespmid33643441 pmcpmc7894590 doi101177 1756286420987031,0.0
development multistudy repository support research veteran health va cooperative studies program epidemiology centerdurham cspecdurham data specimen repository front public health 2021 feb 17 9612806 doi 103389 fpubh2021612806 ecollection 2021abstractfederal agencies including department veterans affairs va prioritized improved access scientific data results collected federally funded research va cooperative studies program epidemiology center durham north carolina cspecdurham assembled repository data specimens collected multiple studies veteran health issues facilitate future research areas developed single protocol request process includes scientific ethical review applications database architecture using metadata common variable descriptors securely store share data across diverse studies addition created mechanism allow data specimens collected older studies reuse addressed study protocol consent forms shared future research within scope original consent cspecdurham data specimen repository currently includes research data genomic data study specimens eg dna blood three content areas colorectal cancer amyotrophic lateral sclerosis gulf war research linking study specimens research data can support additional genetic analyses related research improve veterans healthpmid33681131 pmcpmc7925406 doi103389 fpubh2021612806,0.0
measuring aqueduct sylvius cerebrospinal fluid flow multiple sclerosis using different software diagnostics basel 2021 feb 17 11 2 325 doi 103390 diagnostics11020325abstractaqueduct sylvius aos cerebrospinal fluid flow can quantified using phasecontrast pc magnetic resonance imaging software used aos segmentation might affect pcderived measures analyzed aos pc data 30 people multiple sclerosis 19 normal controls using three software packages estimated crosssectional area csa average highest aos velocity vmean vmax flow rate volume aims assess repeatability reproducibility pcderived measure obtained various software packages including terms group differentiation variables good repeatability except average vmean flow rate volume obtained one software package substantial perfect agreement seen evaluating overlap aos segmentations obtained different software packages variable significantly different software packages exception vmean diastolic peak csa vmax diastolic peak differentiated groups regardless software package conclusion clinical study preliminarily evaluate repeatability order interpret findings vmax seemed repeatable reproducible measure since pixel value usually located center aos thus unlikely affected roi sizepmid33671219 doi103390 diagnostics11020325,0.0
differential contribution cadm1cadm3 cell adhesion molecules peripheral myelinated axons cell adhesion proteins cadm syncam necl family regulate myelination organization myelinated axons peripheral nervous system pns intercellular contact schwann cells underlying axons believed mediated binding glial cadm4 axonal cadm3 cadm2 nevertheless given distinct neurons express different combinations cadm proteins identity functional axonal ligand cadm4 remains determined took genetic approach compare phenotype cadm4 null mice exhibit abnormal distribution caspr kv1 potassium channels mice lacking different combinations cadm1cadm3 genes show contrast mice lacking single cadm1 cadm2 cadm3 genes genetic ablation three phenocopies abnormalities detected absence cadm4 similar defects observed double mutant mice lacking cadm3 cadm2 ie cadm3 cadm2 cadm3 cadm1 ie cadm3 cadm1 mice lacking cadm1 cadm2 ie cadm1 cadm2 furthermore axonal organization abnormalities also detected cadm3 null mice heterozygous two axonal cadms results identify cadm3 main axonal ligand glial cadm4 reveal absence compensated combined action cadm2 cadm1significance statement myelination schwann cells enables fast conduction action potentials along motor sensory axons nerves schwann cellaxon contact mediated cell adhesion molecules cadm family cadm4 schwann cells regulates axonal ensheathment myelin wrapping well organization axonal membrane identity axonal ligands clear reveal cadm mediated axonglia interactions depend hierarchical adhesion code involves multiple family members results provide important insights molecular mechanisms axonglia communication function cadm proteins pns myelin,1.0
embolia cutis medicamentosa subcutaneous injection glatiramer acetate case rep dermatol 2021 feb 16 13 1 114120 doi 101159 000510017 ecollection 2021 janaprabstractembolia cutis medicamentosa ecm rare unpredictable injection site reaction occurring intramuscular subcutaneous even intraarticular injection various drugs report rare case necrotizing ecm injection glatiramer acetate multiple sclerosis include photo documentation entire disease course discuss hypotheses etiology treatmentpmid33790754 pmcpmc7989669 doi101159 000510017,0.0
therapeutic approaches insomnia fatigue patients multiple sclerosis nat sci sleep 2021 feb 16 13201207 doi 102147 nsss256676 ecollection 2021abstractthe prevalence sleep disorders individuals multiple sclerosis ms 35 times higher compared general population insomnia disorder defined difficulty falling asleep maintaining sleep waking early can lead significant fatigue common disabling symptom ms addition fatigue insomnia patients ms also can overlap exacerbate psychological physical symptoms cognitive behavioral therapy insomnia cbti shown effective treatment chronic insomnia burgeoning research demonstrated effectiveness treatment insomnia individuals variety comorbid medical conditions including ms purpose current review will explore literature surrounding prevalence impact sleep disorders fatigue ms additionally review will address practical ways help individuals ms manage fatigue well modify typical standard behavioral treatments insomnia take account special considerations individuals ms based level disability comorbid issues impact sleeppmid33623461 pmcpmc7896778 doi102147 nsss256676,0.0
memantine multiple sclerosis systematic review metaanalysis randomized trials front neurol 2021 feb 15 11574748 doi 103389 fneur2020574748 ecollection 2020abstractbackground multiple sclerosis ms disabling demyelinating disease central nervous system associated cognitive impairment spasticity fatigue still established guidelines management msrelated sequela memantine potential reduce glutamate toxicity thereby reducing consequent cognitive impairment spasticity fatigue objectives study aims determine efficacy safety memantine preventing cognitive impairment reducing spasticity fatigue controlling disability ms patients review relevant randomized trials methods medline central scopus embase lilacs clinicaltrialsgov herdin searched inception may 2020 relevant trials results search yielded 203 articles four studies included analysis pooled evidence shows memantine compared placebo significantly improve pasat ass mfis edss scores patients ms memantine associated mild adverse drug events dizziness fatigue anxiety conclusion enough evidence support efficacy memantine preventing cognitive decline controlling spasticity reducing fatigue preventing disability future researches consider different ms subtypes effect coadministration diseasemodifying therapies longer duration administration sensitive outcome measures evaluate potential benefit memantine mspmid33658967 pmcpmc7917060 doi103389 fneur2020574748,1.0
family planning people multiple sclerosis saudi arabia expert consensus mult scler int 2021 feb 15 20216667006 doi 101155 2021 6667006 ecollection 2021abstractmore half patients multiple sclerosis ms kingdom saudi arabia ksa women childbearing age raising family important life goal women region world however fears misconceptions clinical course relapsingremitting ms rrms effects diseasemodifying drugs dmds foetus led many women reduce expectations raising family sometimes even point avoiding pregnancy altogether increase number dmds available manage rrms recent studies effects pregnancy broadened management options women interferon beta now indication europe use pregnancy according clinical need can used breastfeeding glatiramer acetate possible option women lower levels rrms disease activity become pregnant natalizumab may used 30 weeks patients higher levels disease activity possible physicians need support encourage women pursue dream fulfilling family life supported necessary active interventions rrms increasingly evidence basedpmid33628508 pmcpmc7899766 doi101155 2021 6667006,0.0
preclinical therapy vitamin d3 experimental encephalomyelitis efficacy comparison paricalcitol int j mol sci 2021 feb 15 22 4 1914 doi 103390 ijms22041914abstractmultiple sclerosis ms chronic demyelinating disease central nervous system cns ms animal model called experimental autoimmune encephalomyelitis eae immunopathogenesis involve plethora immune cells whose activation releases variety proinflammatory mediators free radicals vitamin d3 vitd endowed immunomodulatory antioxidant properties demonstrated control eae development however protective effect triggered hypercalcemia compared therapeutic potential vitd paricalcitol pari nonhypercalcemic vitamin d analog control eae seventh day eae induction mice injected vitd pari every day vitd pari displayed downmodulatory ability able reduce recruitment inflammatory cells mrna expression inflammatory parameters demyelination cns lower production proinflammatory cytokines lymph nodederived cells il17 gut explants reduced intestinal inflammation detected eae vitd group compared eae untreated pari groups dendritic cells dcs differentiated presence vitd developed tolerogenic phenotype presence pari findings suggest vitd pari potential used preventive therapy control ms severitypmid33671896 doi103390 ijms22041914,1.0
asymptomatic herpes simplex virus type 1 infection causes earlier onset severe experimental autoimmune encephalomyelitis front immunol 2021 feb 15 12635257 doi 103389 fimmu2021635257 ecollection 2021abstractmultiple sclerosis ms increasingly prevalent progressive autoimmune debilitating chronic disease involves detrimental recognition central nervous system cns antigens immune system although significant progress made last decades biology ms identification novel therapies treat symptoms etiology disease remains unknown however recent studies suggested viral infections may contribute disease onset interestingly potential association herpes simplex virus type 1 hsv1 infection ms reported yet direct relationship among conclusively demonstrated experimental autoimmune encephalomyelitis eae recapitulates several aspects ms humans widely used study disease evaluated effect asymptomatic brain infection hsv1 onset severity eae c57bl 6 mice also evaluated effect infection hsv1mutant attenuated neurovirulence cause encephalitis importantly observed severe eae mice previously infected either wildtype wt mutant hsv1 compared uninfected control mice also earlier eae onset seen wt virus inoculation findings support notion previous exposure hsv1 can accelerate enhance eae suggests potential contribution asymptomatic hsv1 onset severity mspmid33679788 pmcpmc7928309 doi103389 fimmu2021635257,0.0
case report antimog antibody seroconversion accompanied dimethyl fumarate treatment front immunol 2021 feb 15 12625465 doi 103389 fimmu2021625465 ecollection 2021abstracthere report three cases antimyelin oligodendrocyte glycoprotein mog antibodyassociated disease mogad mimicking multiple sclerosis seropositivity antimog antibodies occurred diseasemodifying drug dimethyl fumarate dmf treatment patients developed relapses antimog antibody seroconversion switching fingolimod steroid pulse therapy dmf associated peripheral lymphocyte recovery mogad considered humoral immune disease dmf reportedly enhances th2skewed humoral immune activity therefore suggest dmf fingolimod may exacerbate humoral immune imbalance enhance autoantibody production leading aggravation mogadpmid33659007 pmcpmc7917254 doi103389 fimmu2021625465,1.0
remote administration symbol digit modalities test individuals multiple sclerosis reliable short report mult scler j exp transl clin 2021 feb 14 7 1 2055217321994853 doi 101177 2055217321994853 ecollection 2021 janmarabstractbackground symbol digit modalities test sdmt gold standard cognitive screening multiple sclerosis ms objective due recent covid19 pandemic increased need virtual clinical visits examined reliability remote administration sdmt vs standard inperson administration individuals msmethods pearsons correlation analysis performed sdmt scores inperson remote administrationsresults n 132 participants remote inperson sdmt scores strongly correlated r 80 p 000 conclusion remote administration sdmt reliable cognitive screening approach mspmid33643663 pmcpmc7890734 doi101177 2055217321994853,0.0
binocular vision patients multiple sclerosis clin optom auckl 2021 feb 12 133949 doi 102147 optos286862 ecollection 2021abstractpurpose oculomotor disorders reported multiple sclerosis ms 80 cases studies evaluating binocular vision several neurological diseases ms considering high percentage eyemovement anomalies reported aim study analyze binocular vision subjectsmethods total 59 participants ms 21 monocular optic neuritis eleven binocular optic neuritis 27 without optic neuritis 26 agematched controls enrolled binocular vision analyzed using near point convergence npc positive negative fusional vergence far near distance measurement heterophoria distances cover modified thorington tests randomdot stereoscopyresults percentage subjects abnormal npc values highest ms group followed msonm ms optic neuritis one eye msonb ms optic neuritis eyes control groups ms patients showed esophoric trend near distance positive fusional vergence showed significant differences control ms groups higher variability recovery found ms groups negative fusional vergence near distance showed significant differences control group two ms groups optic neuritis breakpoint recovery values high percentage patients ms alterations stereopsisconclusion alterations binocular vision present ms divergence near distance stereopsis affected parameters likewise ms patients optic neuritis showed worse binocular visionpmid33603529 pmcpmc7886387 doi102147 optos286862,1.0
neurodisparity index nationwide access neurological health care northern ireland front neurol 2021 feb 12 12608070 doi 103389 fneur2021608070 ecollection 2021abstractnationwide disparities managing neurological patients rarely reported compared neurological health care population reside health social care trust tertiary neuroscience center living four nontertiary center trusts northern ireland using tertiary center trust population reference neurodisparity indices ndis defined number treated patients resident trust per 100 000 residents compared ratio tertiary center trust fixed time period ndis calculated four neurological pathwaysintravenous thrombolysis ivtpa mechanical thrombectomy mt acute ischemic stroke ais disease modifying treatment dmt multiple sclerosis ms admissions tertiary neurology ward neurological management recorded 3 026 patients patients resident tertiary center trust likely receive ais treatments ivtpa mt access neurology ward p 0001 patients residing trusts dmt use patients ms higher two nontertiary center trusts tertiary center trust geographical gradient mt ais patients ward admissions averaged ndis nontertiary center trusts 048 95ci 032071 patient admissions tertiary neurology ward 050 95ci 038066 mt ais patients 078 95ci 067092 ivtpa ais patients 111 95ci 099126 dmt use ms patients important neurodisparities northern ireland particularly mt tertiary ward admissions neurologists health service planners aware geography timedependent management neurological patients worsen neurodisparitiespmid33643193 pmcpmc7907594 doi103389 fneur2021608070,0.0
case report borreliadna revealed cause arthritis dermatitis treatment rituximab front neurol 2021 feb 12 12645298 doi 103389 fneur2021645298 ecollection 2021abstractborreliaspecific antibodies serum contribute diagnosis borrelia arthritis borreliaassociated dermatitis young woman ongoing treatment rituximab due multiple sclerosis diagnosis confirmed detection borreliadna skin punch biopsy patient history reveal tick exposure suffered several months fluctuating pain swelling right knee well skin involvement redness oedema around ankle leg monoarthritis confirmed rheumatologist knee puncture performed synovial fluid sufficient microscopic examination crystals neither monosodium urate crystals calcium pyrophosphate crystals found borrelia serology blood revealed borderline levels immunoglobulin ig m igg respectively treatment doxycycline resulted resolution joint skin manifestations within month case highlights borreliaspecific antibody levels reliably interpreted patients received bcell depleting therapy circumstances detection bacterial genome different body fluids skin can useful complement diagnosis lyme disease young female diagnosis certainly delayed without detection borreliadna skinpmid33643217 pmcpmc7907593 doi103389 fneur2021645298,0.0
interviewbased assessment experience cognitive impairment multiple sclerosis cognitive assessment interview cai front neurol 2021 feb 11 12637895 doi 103389 fneur2021637895 ecollection 2021abstractbackground cognitive impairment common feature multiple sclerosis ms semistructured interview including informant input can characterize experience individuals living ms cognitive involvement objective administered cognitive assessment interview cai patient informantbased semistructured interview characterize experience cognitive impairments living ms methods trained raters administered cai sample ms participants informants enrolled trial cognitive remediation cognitive impairments cai characterized compared captured neuropsychological selfreport measures results total n 109 ms participants mean age 503 122 available informants n 71 interviewed participants reported experiencing processing speed 90 106 85 working memory 87 109 80 learning memory 79 109 72 problems commonly caibased ratings moderately correlated selfreport measure multiple sclerosis neuropsychological screening questionnaire r s 052 p 0001 mildly correlated objective neuropsychological measures specific executive functions r s 021 p 0029 informant interviews ratings overall consistent suggesting cai valid even cases informant unavailable interview conducted patient alone often case clinical research settings conclusions cai provides semistructured interview characterize experience cognitive impairment ms findings representing realworld functioning adding valuable information selfreport measures neuropsychological assessmentpmid33643211 pmcpmc7905222 doi103389 fneur2021637895,0.0
role inflammasome neurodegenerative diseases molecules 2021 feb 11 26 4 953 doi 103390 molecules26040953abstractneurodegenerative diseases chronic progressive disorders occur central nervous system cns characterized loss neuronal structure function associated inflammation inflammation cns called neuroinflammation implicated neurodegenerative diseases including alzheimers disease ad parkinsons disease pd amyotrophic lateral sclerosis als multiple sclerosis ms much evidence indicates different conditions share common inflammatory mechanism activation inflammasome complex peripheral monocytes microglia consequent production high quantities proinflammatory cytokines il1 il18 inflammasomes group multimeric signaling complexes include sensor nodlike receptor nlr molecule adaptor protein asc caspase1 nlrp3 inflammasome currently bestcharacterized inflammasome multiple signals potentially provided combination include endogenous danger signals pathogens trigger formation active inflammasome turn will stimulate cleavage release bioactive cytokines including il1 il18 review will summarize results implicating inflammasome pivotal player pathogenesis neurodegenerative diseases discuss compounds hamper activation nlrp3 inflammasome offer novel therapeutic avenues diseasespmid33670164 doi103390 molecules26040953,0.0
clinical predictors driving simulator performance drivers multiple sclerosis abstractbackgrounddrivers multiple sclerosis ms may experience visualcognitive impairment affects fitness drive due limitations associated onroad assessment alternative assessment measures driving performance warranted whether clinical indicators onroad outcomes can also predict driving performance outcomes driving simulator fully understoodobjectivethis study examined deficits immediate verbal auditory recall california verbal learning testsecond edition cvlt2ir slower divided attention useful field view ufov2 predicted deficits operational tactical strategic maneuvers assessed driving simulator drivers without msmethodsparticipants completed cvlt2ir ufov2 driving simulator assessment operational tactical strategic maneuversresultsdeficits immediate verbal auditory recall slower divided attention predicted adjustment stimuli errors pertaining tactical maneuvers 36 drivers ms vs 20 drivers without ms f 3 51 61 p0001 r203 radj202 conclusionthe cvlt2ir ufov2 capture visual verbal auditory recall processing speed divided attention required appropriately adjust stimuli simulated driving environment clinicians may use cvlt2ir ufov2 precursors driving performance deficits drivers ms,0.0
impact sarscov2 infection development neurodegeneration multiple sclerosis int j mol sci 2021 feb 11 22 4 1804 doi 103390 ijms22041804abstractthe novel coronavirus disease 2019 covid19 pandemic caused severe acute respiratory syndrome coronavirus 2 sarscov2 remains global challenge currently information consequences covid19 infection multiple sclerosis ms patients newly discovered coronavirus farreaching effects participation neurodegenerative diseases seem significant recent cases reports showed sarscov2 may responsible initiating demyelination process people previously symptoms associated nervous system disorders presently known infection sarscov2 evokes cytokine storm syndrome may one factors leading acute cerebrovascular disease one substantial problems coexistence cerebrovascular disease ms individuals life span epidemiological studies showed enhanced risk death rate vascular disabilities ms patients approximately 30 demonstrated patients severe sarscov2 infection usually show increased levels ddimer fibrinogen creactive protein crp overactivation blood platelets essential elements prothrombotic events review latest knowledge gathered ongoing pandemic sarscov2 infection neurodegeneration processes ms discussedpmid33670394 doi103390 ijms22041804,1.0
impact excipients stability polymer microparticles autoimmune therapy front bioeng biotechnol 2021 feb 11 8609577 doi 103389 fbioe2020609577 ecollection 2020abstracttherapies autoimmune diseases multiple sclerosis diabetes curative cause significant challenges patients include frequent continued treatments required throughout lifetime patient well increased vulnerability infection due nonspecific action therapies biomaterials enabled progress antigenspecific immunotherapies carriers delivery vehicles immunomodulatory cargo however work preclinical stage small dosing requirements allow ondemand preparation immunotherapies clinical translation potential immunotherapies manufacturing preservation storage stability critical parameters require greater attention tested stabilizing effects excipients lyophilization polymeric microparticles mps designed autoimmune therapy mps loaded peptide selfantigen small molecule immunomodulator synthesized lyophilized particles three clinically relevant excipients mannitol trehalose sucrose biophysical properties formulations assessed function excipient formulation stage addition formulations evaluated primary immune cell culture manufacturing perspective excipients improved caking lyophilized product enabled complete resuspension increased product recovery led smaller changes mp size size distribution time cocultures antigenpresenting cells selfreactive t cells revealed mps lyophilized excipients maintained toleranceinducing function even significant storage times without refrigeration data demonstrate excipients can selected drive favorable manufacturing properties without impacting immunologic properties tolerogenic mpspmid33644005 pmcpmc7906284 doi103389 fbioe2020609577,0.0
new methods posturographic data analysis may improve diagnostic value static posturography multiple sclerosis heliyon 2021 feb 11 7 2 e06190 doi 101016 jheliyon2021e06190 ecollection 2021 febabstractbackground early accurate diagnosis multiple sclerosis ms crucial effective treatment ms diagnostic neuronal networks control posture movement particular importance performance can assessed using static posturography unfortunately commercially available posturographic platforms equipped appropriate proceduresmethods solve problem postural sway trajectories recorded 55 ms patients standing quiet eyes open eo eyes closed ec trajectories analyzed using novel methods postural sway parametrization including sway stability vector sv anteroposterior mediolateral sway indices diap diml results results exhibited unique postural sway patterns may attributed ms novel parametrization methods postural sway showed pathology specific increase postural sway velocity ec tests additionally documented abnormal alterations anteroposterior ap mediolateral ml sway indices also uniquely dependent visual input ec tests patients exhibited characteristic pattern sway increase ap ml directions correlated advance disease measured edss kurtzke scale functional system scoresconclusions applied present study novel posturographic metrics give assessment diagnostic value allows us recommend static posturography test simple safe supplementary clinical tool diagnosis ms assessment ms pathology effects treatment impact vision sway stability vector seems important factorpmid33659736 pmcpmc7892908 doi101016 jheliyon2021e06190,0.0
coping strategies seeking personalized care relapsingremitting multiple sclerosis patient reported measurecoping responses inventory mult scler j exp transl clin 2021 feb 11 7 1 2055217320987588 doi 101177 2055217320987588 ecollection 2021 janmarabstractcoping defined set cognitive behavioral efforts made master stressful specific demands adaptation chronic diseases multiple sclerosis ms depends effectiveness coping objective assess psychometric properties coping responses inventory cria persons ms pwms verifying transferability measure already validated argentine general population describe types coping strategies available pwms methods 90 pwms included outcome measures cria inventory expanded disability status scale edss beck depression inventory fatigue severity scale ms international quality life questionnaire results descriptive data follows mean age years 4097 1285 years education 1346 393 edss 248 179 disease evolution years 1076 972 depression 1392 1045 fatigue 377 172 psychometric properties cria inventory observed argentine general population present ms sample well adequate validity reliability respondents frequently utilized problemfocused coping style conclusions results showed cria good transferability properties argentine general population ms populationpmid33633866 pmcpmc7887687 doi101177 2055217320987588,0.0
autologous haematopoietic stem cell transplantation firstline diseasemodifying therapy patients aggressive multiple sclerosis abstractbackgroundautologous haematopoietic stem cell transplantation ahsct effective treatment patients multiple sclerosis ms highly active disease despite use standard diseasemodifying therapies dmts however optimal time offering ahsct patients aggressive ms yet establishedobjectivesthe objective explore safety efficacy ahsct firstline dmt patients aggressive msmethodsall patients aggressive ms received ahsct firstline dmt five european north american centres retrospectively evaluatedresultstwenty patients identified median interval diagnosis ahsct 5 120 months multiple poor prognostic markers median pretransplant expanded disability status scale edss score 50 1595 median followup 30 12118 months median edss score improved 20 065 p00001 patient relapses three residual magnetic resonance imaging mri disease activities first 6months posttransplant new enhancing lesions observed subsequent scansconclusionahsct safe effective firstline dmt inducing rapid sustained remission patients aggressive ms,0.0
enhancement myogenic potential muscle progenitor cells muscle healing pregnancy abstractthe decline muscle regenerative potential age attributed diminished responsiveness muscle progenitor cells mpcs heterochronic parabiosis used model study effects aging stem cells niches studies demonstrated exposing old mice young systemic environment aged progenitor cells can rejuvenated one interesting idea pregnancy represents unique biological model naturally shared circulatory system developing mature organisms test hypothesis evaluated muscle regeneration potential pregnant mice using cardiotoxin ctx injury mouse model results indicate pregnant mice demonstrate accelerated muscle healing compared nonpregnant control mice following muscle injury based improved muscle histology superior muscle regeneration reduction inflammation necrosis additionally found mpcs isolated pregnant mice display significant improvement myogenic differentiation capacity vitro muscle regeneration vivo compared mpcs nonpregnant mice furthermore mpcs nonpregnant mice display enhanced myogenic capacity cultured presence serum obtained pregnant mice proteomics data studies provides potential therapeutic targets enhance myogenic potential progenitor cells muscle repair,0.0
engine failure axomyelinic signaling potential key player pathogenesis multiple sclerosis front cell neurosci 2021 feb 10 15610295 doi 103389 fncel2021610295 ecollection 2021abstractmultiple sclerosis ms complex chronic disease central nervous system cns characterized degenerative inflammatory processes leading axonal damage demyelination neuronal loss last decade traditional outsidein standpoint ms pathogenesis identifies primary autoimmune inflammatory etiology challenged complementary insideout theory focusing degenerative processes ms axomyelinic system may reveal new insights disease triggering mechanisms oxidative stress os widely described one means driving tissue injury neurodegenerative disorders including ms axonal mitochondria constitute main energy source electrically active axons neurons largely vulnerable oxidative injury consequently axonal mitochondrial dysfunction might impair efficient axoglial communication turn affect axonal integrity maintenance axonal neuronal synaptic signaling review article argue osderived mitochondrial impairment may underline dysfunctional relationship axons supportive glia cells specifically oligodendrocytes mechanism implicated development primary cytodegeneration secondary proinflammatory response insideout turn together variably primed hosts immune system may lead onset ms different subtypespmid33642995 pmcpmc7902503 doi103389 fncel2021610295,1.0
neurobiology covid19 can virus affect brain severe acute respiratory syndromerelated coronavirus2 sarscov2 causes coronavirus disease 2019 covid19 declared public health emergency international interest confirmed cases countries covid19 presents manifestations can range asymptomatic mild infections severe manifestations lead hospitalization death growing amount evidence indicates virus may cause neuroinvasion postmortem brain study findings included edema hemorrhage hydrocephalus atrophy encephalitis infarcts swollen axons myelin loss gliosis neuronal satellitosis hypoxicischemic damage arteriolosclerosis leptomeningeal inflammation neuronal loss axon degeneration addition covid19 pandemic causing dangerous effects mental health world population can attributed social impact social distancing financial issues quarantine also concern environmental stressors enhanced psychological factors contributing emergence psychiatric outcomes pandemic although clinical studies diagnosing sarscov2related neurological disease can challenging necessary help define manifestations burden covid19 neurological psychiatric symptoms pandemic review aims present neurobiology coronavirus postmortem neuropathological hallmarks,1.0
interpret restingstate fmri ask participants restingstate fmri rsfmri reveals brain dynamics taskunconstrained environment subjects let minds wander freely consequently resting subjects navigate rich space cognitive perceptual states ie ongoing experience ongoing experience shapes rsfmri summary metrics eg functional connectivity unknown yet likely contribute uniquely within betweensubject differences argue understanding role ongoing experience rsfmri requires access standardized temporally resolved scientifically validated firstperson descriptions experiences suggest best practices obtaining descriptions via introspective methods appropriately adapted use fmri research conclude set guidelines fusing two data types answer pressing questions etiology rsfmri,0.0
role tim3#x2f galectin9 pathway tcell function prognosis patients human papilloma virusassociated cervical carcinoma abstractthe interaction tim3 t cell ligand galectin9 negatively regulates cellular immune responses however role tim3 galectin9 pathway immune evasion cervical cancer remains unknown study investigate expression function regulation tim3 galectin9 signaling pathway human papilloma virus hpv positive cervical cancer flow cytometry showed tim3 expression t cell galectin9 expression monocytes hpv positive cervical cancer patients significantly higher compared cervical intraepithelial neoplasia benign uterine fibroids tim3+cd4+ th1 cells tim3+cd8+ t cells hpv positive cervical cancer patients significantly reduced surgery serum tgf il10 levels positively correlated tim3+treg cells ifn il2 negatively correlated tim3+th1 cells additionally tim3+cd4+ t cells positively correlated galectin9+monocytes survival curve analysis showed tim3+cd4+ t cells negatively correlated patient survival closely related figo stage degree differentiation lymph node metastasis hpv positive cervical cancer vitro experiments showed blocking tim3 galectin9 pathway proliferation t cells ability express ifn il2 perforin granzyme b significantly restored conclusion high levels tim3 galectin9 hpv positive cervical cancer patients play roles progression disease promoting treg cells inhibit cytotoxic function th1 cd8+ t cells tim3 galectin9 may serve new immunotherapy target patients hpv positive cervical cancer,0.0
role monoclonal antibody quot alemtuzumabquot treatment multiple sclerosis cureus 2021 feb 9 13 2 e13246 doi 107759 cureus13246abstractthis article will review current treatment options multiple sclerosis ms keeping primary focus alemtuzumab now approved 65 countries pathophysiological point view ms disabling disease impacting patients life physically mentally leading devastating social economic impact review will elaborate alemtuzumabs role treating relapsingremitting ms rrms comparing efficacy side effects monitoring diseasemodifying therapies dmts available market point great concern physicians also neurologists nephrologists endocrinologists dermatologists oncologists encountering longterm effects alemtuzumab life treated ms patients hope review will benefit treating faculties also suffering devastating diseasepmid33728194 pmcpmc7948316 doi107759 cureus13246,0.0
preventing treating neurological disorders flavonol fisetin brain plast 2021 feb 9 6 2 155166 doi 103233 bpl200104abstractneurological disorders including neurodegenerative diseases significant negative impact patients society large since prevalence disorders increases age consequences aging population going grow now acknowledged neurological disorders multifactorial involving disruptions multiple cellular systems disorder specific initiating mechanisms pathologies certain common pathways appear involved neurological disorders thus becoming increasingly important identify compounds can modulate multiple pathways contribute disease development progression one compounds flavonol fisetin fisetin now shown preclinical models effective preventing development progression multiple neurological disorders including alzheimers disease parkinsons disease huntingtons disease amyotrophic lateral sclerosis stroke ischemic hemorrhagic traumatic brain injury well reduce ageassociated changes brain beneficial effects stem actions multiple pathways associated different neurological disorders actions include well characterized antiinflammatory antioxidant effects well recently described effects regulated cell death oxytosis ferroptosis pathway gut microbiome senolytic activity therefore growing body preclinical data along fisetins ability modulate large number pathways associated brain dysfunction strongly suggest worthwhile pursue therapeutic effects humanspmid33782648 pmcpmc7990461 doi103233 bpl200104,0.0
predisposing factors sexual dysfunction multiple sclerosis front neurol 2021 feb 9 12618370 doi 103389 fneur2021618370 ecollection 2021abstractsexual dysfunction sd people multiple sclerosis pwms detrimental impact individual healthrelated quality life hrqol clear whether sd multiple sclerosis ms independent symptom merely byproduct symptoms depression anxiety crosssectional study 93 pwms determines risk factors sd ms based prevalence hrqol associated disease outcomes diagnosis sd determined based multiple sclerosis intimacy sexuality questionnaire19 msisq19 correlated physical disability measured expanded disability status scale edss depression anxiety hospital anxiety depression scale hads hrqol multiple sclerosis quality life54 msqol54 multivariate regression models performed determine independent risk factors sd pwms almost half participants study 46 reported sd hrqol significantly poorer patients ms suffering sd median iqr msqol54 scores physical subscale 52 4168 vs 81 6989 p 0001 mental subscale 50 3882 vs 86 7089 p 0001 multivariate model edss independent risk factor sd 181 edss 4 95 ci 33314 p 0001 depression anxiety conclude risk sd growing increasing edss independent depression anxiety screening sd becomes particularly relevant patients growing disabilitypmid33633671 pmcpmc7900565 doi103389 fneur2021618370,0.0
astrocytic oligodendrocytic p2x7 receptors determine neuronal functions cns front mol neurosci 2021 feb 9 14641570 doi 103389 fnmol2021641570 ecollection 2021abstractp2x7 receptors members atpgated cationic channel family preferential localization microglial cells resident macrophages brain however receptors also present neuroglia astrocytes oligodendrocytes although considerably lower density mediate necrosis apoptosis release proinflammatory cytokines chemokines reactive oxygen species ros well excitotoxic glio transmitters glutamate atp besides mediating cell damage ie superimposed upon chronic neurodegenerative processes alzheimers disease parkinsons disease multiple sclerosis amyotrophic lateral sclerosis may also participate neuroglial signaling neurons conditions high atp concentrations form neuroinflammation neurodegeneration pertinent open question whether p2x7rs localized neurons whether neuroglia microglia possess receptortype causing indirect effects releasing abovementioned signaling molecules suggest based molecular biology functional evidence neurons devoid p2x7rs although existence neuronal p2x7rs excluded absolute certaintypmid33642994 pmcpmc7906075 doi103389 fnmol2021641570,0.0
motor sequence learning across multiple sessions facilitated targeting consolidation posttraining tdcs patients progressive multiple sclerosis neural plast 2021 feb 9 20216696341 doi 101155 2021 6696341 ecollection 2021abstractcompared relapsingremitting multiple sclerosis ms progressive ms characterized lack spontaneous recovery poor response pharmaceutical immunomodulatory treatment patients may therefore particularly benefit interventions augment traininginduced plasticity central nervous system crosssectional doubleblind crossover pilot study effects transcranial direct current stimulation tdcs motor sequence learning examined across four sessions days 1 3 5 8 16 patients progressive ms active sham anodal tdcs primary motor cortex applied immediately training session participants took part two experiments separated least four weeks differed respect type posttraining tdcs active sham task performance across blocks training across sessions improved significantly active sham tdcs experiment neither online offline motor learning modulated type tdcs accordingly primary endpoint task performance day 8 differ stimulation conditions sum patients progressive ms able improve performance ecologically valid motor sequence learning task training however even multisession posttraining tdcs fails promote motor learning progressive mspmid33790962 pmcpmc7984928 doi101155 2021 6696341,0.0
brain atrophy clinical characteristics predicting sdmt performance multiple sclerosis 10year followup study mult scler j exp transl clin 2021 feb 8 7 1 2055217321992394 doi 101177 2055217321992394 ecollection 2021 janmarabstractobjectives identify magnetic resonance imaging mri clinical demographic biomarkers predictive worsening information processing speed ips measured symbol digit modalities test sdmt methods demographic clinical data 15 t mri scans collected 76 patients time inclusion 5 10 years global tissuespecific volumes calculated time point primary outcome analysis sdmt usedresults worsening sdmt 5year followup predicted baseline age expanded disability status scale edss sdmt whole brain volume wbv t2 lesion volume lv explaining 302 variance sdmt 10year followup age edss grey matter volume gmv t1 lv explained 394 variance sdmt changeconclusion longitudinal study shows baseline mrimarkers demographic clinical data can help predict worsening ips identification patients risk ips decline importance followup treatment rehabilitation can optimizedpmid33623706 pmcpmc7876764 doi101177 2055217321992394,0.0
established novel therapeutic options autoimmune hepatitis summaryautoimmune hepatitis immunemediated disorder characterised hypergammaglobulinaemia autoantibodies interface hepatitis mainstay treatment nonspecific immunosuppression consisting steroids without azathioprine although patients respond satisfactorily steroid thiopurinebased treatment regimens 40 relapse 10 undergo liver transplantation cause autoimmune hepatitis unknown evidence implicates genetic environmental factors pathogenesis imbalance effector regulatory mechanisms leads breakdown immune tolerance consequent development autoimmune attack signalling pathways implicated pathogenesis autoimmune hepatitis involve proinflammatory cytokines interferon il12 tumour necrosis factor il6 il23 numerical functional defects regulatory t cells permissive role enables autoimmune liver injury occur persist new therapeutic strategies needed aim obtaining longlasting disease remission without inducing nonspecific immunosuppression focus inhibiting intrahepatic proinflammatory milieu expanding pool regulatory t cells,0.0
tension trauma releasing exercises people multiple sclerosis exploratory pilot study j tradit complement med 2021 feb 8 11 5 383389 doi 101016 jjtcme202102003 ecollection 2021 sepabstractbackground aim multiple sclerosis ms characterized increasing symptom burden leading many people ms use complementary treatments tre tension trauma releasing exercises mindbody therapeutic method aiming release muscle tension stress people ms pwms reported benefits tre scientific studies investigated effects tre pwms aim test tre program pwms thereby explore outcome measures applied future randomized studiesexperimental procedure nineweek tre program completed nine participants five women age ranged 44 66 years time since diagnosis ranged 2 21 years outcome measures included selfreported daytoday levels nine different symptoms well sleep quality stress level modified fatigue impact scale mfis fatigue score spasticity level ankle plantar flexors assessed using portable spasticity assessment device psad measured pre post interventionresults decreases seen mean scores nine selfreported daytoday symptoms well stress level sleep quality mean score increased lme analyses showed changes statistically significant except one bowel dysfunction mean mfismeasured fatigue level decreased significantly score 437 sd 136 score 220 sd 123 significant change reported psadmeasured spasticity levelconclusion study indicates possible effects tre pwms several selfreported outcome measures larger randomized studies carried explore findings furtherpmid34522632 pmcpmc8427467 doi101016 jjtcme202102003,0.0
evidence mycobacteria associated pathogenesis sjogren#39 s syndrome j transl autoimmun 2021 feb 5 4100085 doi 101016 jjtauto2021100085 ecollection 2021abstractsjogrens syndrome ss common systemic autoimmune disorder primarily affecting exocrine glands resulting xerostomia xerophthalmia ss may also manifest polyarthralgia polyarthritis polymyalgia cutaneous organ vasculitis interstitial lung disease various disorders primary autoantibodies associated ss used adjuncts diagnosis antiro ssa antila ssb pathogenesis ss considered involve genetic susceptibility environmental triggers identified genetic susceptibility ss lies variants tumor necrosis factor alpha inducible protein 3 tnfaip3 gene product known a20 deficiency dysfunction a20 known induce macrophage inflammatory response mycobacteria potentially increasing repertoire mycobacterial antigens available predisposing autoimmunity via paradigm molecular mimicry ie providing mechanistic link genetic susceptibility ss exposure environmental nontuberculous mycobacteria ntm mycobacterium avium ss paratuberculosis map ntm causes johnes disease enteritis ruminant animals humans broadly exposed map antigens environment food products infected animals map also implicated environmental trigger number autoimmune diseases via cross reactivity heat shock protein 65 hsp65 hostspecific proteins context ss mycobacterial hsp65 shares epitope homology ro la proteins recent study showed strong association ss antibodies mycobacterial hsp65 association validated important determine whether bacillus calmetteguerin bcg vaccination known protective ntm likely epigenetic alteration innate adaptive immunity antimycobacterial drugs decrease mycobacterial antigenic load may preventive therapeutic role ss evidence support concept bcg shown benefit type 1 diabetes mellitus multiple sclerosis autoimmune diseases linked map via hsp65 diseasespecific autoantibodies conclusion number factors lend credence notion pathogenic link environmental mycobacteria ss including presence antibodies mycobacterial hsp65 ss homology hsp65 ss autoantigens beneficial effects seen bcg vaccination certain autoimmune diseases furthermore given bcg may protect ntm immune modifying effects strong safety record billions doses given bcg antimycobacterial therapeutics studied sspmid33665595 pmcpmc7902540 doi101016 jjtauto2021100085,0.0
effect cannabis clinical cytokine profiles patients multiple sclerosis mult scler int 2021 feb 5 20216611897 doi 101155 2021 6611897 ecollection 2021abstractbackground multiple studies reported cannabis administration multiple sclerosis patients associated decreased symptom severity study conducted evaluate prevalence cannabis abuse multiple sclerosis cases evaluate effect cannabis serum cytokines cases patients methods total 150 multiple sclerosis cases along 150 healthy controls included study period cases subjected history taking neurological examination routine investigations cases asked cannabis intake confirmed urine test serum cytokines including il1 il2 il4 il10 il12 il17 il22 ifn ifn1 tnf ordered cases controlsresults twentyeight cases cannabis abusers ms cannabis group 1867 remaining 122 cases represented ms group significant difference three groups regarding age disease duration ms type male gender predominant ms cannabis group number relapses significantly lower group fifteen cases 536 reported symptoms improved cannabis proinflammatory cytokines significantly elevated ms group compared ms cannabis control groups additionally antiinflammatory cytokines significantly lower values ms group compared ms cannabis control groups clinical symptoms significantly improved ms cannabis group compared ms group apart sexual dysfunction bladder symptoms visual disturbances mild side effects cannabis also reportedconclusion cannabis may positive impact cytokine clinical profiles cases multiple sclerosispmid33628507 pmcpmc7884151 doi101155 2021 6611897,1.0
vitamin d status disability among patients multiple sclerosis systematic review metaanalysis aims neurosci 2021 feb 5 8 2 239253 doi 103934 neuroscience2021013 ecollection 2021abstractassociation serum vitamin d level disability patients multiple sclerosis ms investigated several researches however studies reported different results current study aims estimate correlation concentrations 25 oh vitamin d level disability among ms patients using mesh nonmesh terms related ms disability level vitamin d different data banks searched required information extracted selected eligible primary articles stata version 11 software applied combining primary correlation coefficients using random effect model effect ms type patients age assessed using metaregression models sensitivity analysis performed investigate role primary study pooled estimate egger test applied find publication bias 14 eligible studies total correlation coefficient 95 confidence interval 25 oh vitamin d level disability sexes well among female estimated 029 040 017 035 046 024 respectively two articles carried among male report significant results metaanalysis showed significant negative correlation 25 oh vitamin d level disability ms patients disability reduces increasing 25 oh vitamin d levelpmid33709027 pmcpmc7940116 doi103934 neuroscience2021013,0.0
correlation dietary intake helicobacter pylori infection multiple sclerosis casecontrol study rafsanjan iran 201718 qatar med j 2021 feb 5 2020 3 45 doi 105339 qmj202045 ecollection 2020abstractbackground multiple sclerosis ms autoimmune disease affecting central nervous system environmental factors helicobacter pylori infection hpi likely considered protective factor ms dietary intake may provide exposure protective effects ms present study aimed determine relationship serum antih pylori igg antibody hpia level dietary intake patients ms referred ms clinic rafsanjan city iranmethods present casecontrol study conducted 97 patients ms 95 controls two groups significant difference age gender p 005 hpia checked food frequency questionnaire completed groups measure nutritional intake data analyzed spss 20 software using independent ttest chisquare mannwhitney u test correlationresults median serum hpia level significantly lower ms cases controls furthermore median consumption glutamic acid arginine serine aspartic acid alanine proline caffeine significantly lower ms cases controls significant positive correlation found levels linoleic acid lactose ca molybdenum galactose leucine valine level hpia controlsconclusion study results demonstrated dietary nutrients correlations ms hpi therefore professionals multiple disciplines must find foods contain dietary nutrients future studiespmid33623753 pmcpmc7878158 doi105339 qmj202045,0.0
sensitivity analysis primary endpoint nmomentum study inebilizumab nmosd abstractbackgroundin nmomentum trial risk adjudicated neuromyelitis optica spectrum disorder nmosd attack significantly reduced inebilizumab compared placeboobjectiveto demonstrate robustness finding using prespecified sensitivity subgroup analysesmethodsnmomentum prospective randomized placebocontrolled doublemasked trial inebilizumab anticd19 monoclonal bcelldepleting antibody patients nmosd preplanned post hoc analyses performed evaluate primary endpoint across range attack definitions demographic groups well key secondary endpointsresultsin nmomentum trial clinicaltrialsgov nct02200770 174 participants received inebilizumab 56 received placebo attack risk inebilizumab versus placebo consistently significantly reduced regardless attack definition type attack baseline disability ethnicity treatment history disease course hazard ratios 04 favoring inebilizumab p 005 analyses secondary endpoints showed similar trendsconclusionnmomentum demonstrated inebilizumab provides robust reduction risk nmosd attacks regardless attack evaluation method attack type patient demographics previous therapythe nmomentum study registered clinicaltrialsgov nct2200770,0.0
compressive cervical myelopathy patients demyelinating disease central nervous system improvement surgery despite late diagnosis cureus 2021 feb 5 13 2 e13161 doi 107759 cureus13161abstractobjective aimed assess impact surgical intervention outcome patients diagnosed demyelinating disorders cervical degenerative disease warranting surgical intervention methods records patients diagnosis demyelinating disorder central nervous system underwent cervical spine surgery single institution 2016 2020 reviewed demyelinating disease included multiple sclerosis ms neuromyelitis optica transverse myelitis tm dates initial spine symptom onset recognition spinal pathology primary provider referral spine surgery spine surgery procedures collected hospital length stay los postoperative outcomes complications recorded results total 19 patients diagnosis demyelinating disorders underwent cervical spine surgery institution seventeen patients ms average time interval documented diagnosis myelopathy radiculopathy referral spine clinic 6795 months m40 sd6487 twelve patients imaging studies depicting degenerative spine disease warrant surgical intervention time examination primary physician average delay referral spine clinic patients 165 months m5 sd2536 89 patients experienced significant neurologic improvement postoperatively conclusions delay recognition cervical spine disease amenable surgical resolution patients demyelinating disorders surgical treatment can lead significant clinical improvement patient population even delayed likely carries similar risk general populationpmid33728163 pmcpmc7935266 doi107759 cureus13161,1.0
incidence clinical outcome coronavirus disease 2019 cohort 11 560 brazilian patients multiple sclerosis abstractbackgroundlittle information available regarding incidence clinical outcome sarscov2 infection patients multiple sclerosis pwms objectiveto determine incidence clinical outcome impact covid19 pwmsmethodsthis observational study prospectively performed cohort pwms n 11 560 followed 47 51 brazilian ms referral centers registered pwms covid19 redone platform 13 march 4 june 2020resultsthe incidence covid19 pwms patients 277 10 000 patients general population 292 10 000 inhabitants total 94 77 women pwms patients aged 40 1025years presenting 99 86years ms disease duration developed covid19 87 exhibited mild form disease eighty 96 patients maintained use ms diseasemodifying treatment dmt covid19 pandemic 14 patients use dmtsconclusionincidence covid19 brazilian pwms different observed general brazilian population pwms exhibited mild covid19 despite maintenance underlying ms treatment,0.0
neuroimmunology chronic pain rodents humans chronic pain encompassing conditions low back pain arthritis persistent postsurgical pain fibromyalgia neuropathic pain disorders highly prevalent remains poorly treated vast majority therapeutics directed solely neurons despite fact signaling immune cells glia neurons now recognized indispensable initiation maintenance chronic pain review highlights recent advances understanding fundamental neuroimmune signaling mechanisms novel therapeutic targets rodent models chronic pain discuss new technological developments study diagnose quantify neuroimmune contributions chronic pain patient populations,0.0
quantifying upper limb tremor people multiple sclerosis using fast fourier transform based analysis wrist accelerometer signals j rehabil assist technol eng 2021 feb 3 82055668320966955 doi 101177 2055668320966955 ecollection 2021 jandecabstractintroduction tremor disabling symptom multiple sclerosis ms development objective methods tremor characterisation assess intervention efficacy disease progression therefore important possibility using fast fourier transform fft method tremor detection exploredmethods acceleration wristworn device analysed using ffts identify characterise tremor magnitude frequency processing parameters explored provide insight optimal algorithm participants wore wrist triaxial accelerometer 9 tasks fahn clinical assessment tremor used reference standardresults five people ms tremor 576 153 years 3 f 2m ten diseasefree controls 424 109 years 5 m 5f took part using specific algorithm settings tremor identification possible peak frequency 315hz magnitude greater 006 g 2 s windows 50 overlap using 2 3 axes acceleration giving sensitivity 0974 specificity 0971 38 tremor occurrences 108 tasks 1 false positive 2 false negatives tremor frequency 35130 hz amplitude 007260gconclusions upper limb tremor people ms can detected using fft approach based acceleration recorded wrist demonstrating possibility using minimally encumbering technique within clinical practicepmid33614109 pmcpmc7869147 doi101177 2055668320966955,0.0
neurofibromatosis type 1 highly active relapsingremitting multiple sclerosis rrms eur j case rep intern med 2021 feb 3 8 3 002190 doi 1012890 2021_002190 ecollection 2021abstractneurofibromatosis type 1 nf1 autosomal dominant neurocutaneous disease confers increased risk malignant tumour development relapsing remitting multiple sclerosis rrms inflammatory demyelinating disease central nervous system coexistence multiple sclerosis nf1 rare reported describe case 31yearold man nf1 subacute walking problems proximal pain lower limbs successfully treated natalizumablearning points coexistence multiple sclerosis ms neurofibromatosis type 1 nf1 rare described literaturefollowup patients nf1 important early detection management ms can prevent disabilityappropriate treatment physical therapy can improve patients activity social lifepmid33768065 pmcpmc7977044 doi1012890 2021_002190,1.0
can tetracyclines ensure help multiple sclerosis immunotherapy j clin transl res 2021 feb 3 7 1 2233 ecollection 2021 feb 25abstractbackground multiple sclerosis ms disease central nervous system autoimmune response leads chronic inflammation represents second leading cause nontraumatic disability world affecting mainly young adults high female male incidence present causative agent ms unknown preventing development prophylaxis policies understanding human system copes complex inflammation tetracyclines tet attracted great attention due antiinflammatory effects minocycline doxycycline represent secondgeneration tet largely used treat acne suppress inflammation addition safer cheaper drugs currently used treat msaim study aims review recent data involving tet minocycline doxycycline therapeutic potential msrelevance patients many drugs used treat ms severe side effects costly tet hand safe inexpensive class drugs can modulate immune response ms patientspmid34104806 pmcpmc8177043,0.0
design considerations multiple sclerosis fatigue mobile app ms energize pragmatic iterative approach using usability testing resonance checks internet interv 2021 feb 2 24100371 doi 101016 jinvent2021100371 ecollection 2021 aprabstractmultiple sclerosis ms chronic neurological condition affecting around 22 million people worldwide illness includes range symptoms fatigue considered one disabling paper describes pragmatic iterative approach supported usability resonance testing used build minimum viable product ms energizeor ms energise uk english regions ms energise mobile application focused selfmanagement fatigue people ms iterative approach included various stages testing user feedback including comments interface navigation content sought inform incremental app development continual improvement usability testing conducted 11 people longstanding multiple sclerosis new zealand united kingdom focused particular sections app well accessibility app users ms two participants contributed resonance testing postrelease ensure app perceived relevant useful user usability testing resonance testing phases suggested user experience ms energise mostly positive participants provided number suggestions improvements aspects content design implemented app development process findings will also contribute future planning design iteration enhance user experience next step improvement ms energise prior trial clinical cost effectivenesspmid33614414 pmcpmc7878181 doi101016 jinvent2021100371,0.0
ultrastructural clarification peripherally located actin network myelinated axons despite existence large amount actin axons concentration factin quite low myelinated axons almost factin located peripheries myelinated axons now ultrastructural localization factin still reported myelinated axons probably due lack appropriate detection method present study phalloidinbased fitcantifitc technique adopted investigate subcellular localization factin myelinated axons using technique factin located outer inner collars myelinated cytoplasm surrounding intermodal axon schmidtlanterman incisures paranodal terminal loops nodal microvilli addition satellite cell envelope encapsulates axonal initial segment peripheral sensory neuron also demonstrated factinenriched structure study provided hitherto unreported ultrastructural view factin myelinated axons may assist understanding unique organization axonal actin cytoskeleton,1.0
coachms innovative closedloop interdisciplinary platform monitor proactively treat ms symptoms pilot study mult scler j exp transl clin 2021 feb 2 7 1 2055217321988937 doi 101177 2055217321988937 ecollection 2021 janmarabstractbackground numerous challenges treating cooccurring symptoms multiple sclerosis ms objective pilot feasibility novel symptom management platform coachms monitor ms symptoms bladder function ambulation mood bam respond changes realtimemethods 12week randomized controlled pilot trial participants symptoms monitored using weekly questionnaires remote ambulatory monitoring fitbit flex2 behavioral change principles used included shared goal setting 2 weeks weeks 212 coachms group received targeted contact interventions symptoms worsened control group treated usual clinic practice outcomes feasibility retention adherence acceptability primary proportion recommended treatments pursued secondary efficacy exploredresults 21 participants enrolled 13 62 completed study protocol adherence excellent coachms participants demonstrated greater followthrough clinical recommendations controls 93 95 ci 09 976 cohort bam symptom tended improve suicidality detected one control participant resulting urgent evaluation hospitalizationconclusions innovative coachms platform feasible acceptable cohort baseline bam symptoms represent accessible costeffective tool monitor ms symptoms realtime larger trial plannedpmid33796329 pmcpmc7970691 doi101177 2055217321988937,0.0
therapeutic targets fingolimod fty720 involved pathological processes frontal cortex alzheimers disease patients network pharmacology study front aging neurosci 2021 feb 2 13609679 doi 103389 fnagi2021609679 ecollection 2021abstractbackground sphingosine1phosphate receptor s1pr modulator fingolimod fty720 commonly used immunomodulator multiple sclerosis treatment recently found reduce pathological changes brain tissue alzheimers disease ad animal models yet verified human brain tissue study network pharmacology methods applied determine potential pharmacological mechanisms fingolimod frontal cortex ad patients methods pharmacological macromolecular targets fingolimod fingolimod phosphate downloaded swisstarget drugbank systematic intersection analysis expression profiles brain frontal cortex tissues 423 ad tissues 266 control tissues performed obtain adassociated fingolimod targets fadgs immune cell infiltration analysis primary mouse cortical culture rnaseq drug screen database used identify immunerelated fadgs cortexrelated fadgs expression values fadgs correlated disease severity score mmse score ad patients identify severityrelated fadgs also analyzed mirna expression microarray data frontal cortex ad patients associated disease severity obtain severityrelated fadgmirnas results total 188 fadgs detected frontal cortices ad patients enriched biological processes synaptic signaling inflammatory response response oxygencontaining compounds eleven immunerelated fadgs like fpr1 blnk 17 cortexrelated fadgs like aldh1l1 dusp1 detected fadgs s1pr1 gabbr2 although classified two categories still predicted bioinformatics methods play important role development ad two fadgs gnaq mmp14 28 mirnas like mir 323a3p mir181a5p found associated ad severity mmse 027 group fifteen fadgs like aldh1l1 fpr1 il6 46 mirnas like mir2125p mir935p found associated mild moderate dementia ad patients severity mmse1122 subgroup conclusions fingolimod may affect brain frontal cortex function ad patients many different ways affecting immune cell infiltration nerve cell glial cell function synaptic function mirnas may also involved aldh1l1 fpr1 s1pr1 gabbr2 may core drug targetspmid33603656 pmcpmc7884771 doi103389 fnagi2021609679,0.0
paediatric multiple sclerosis antibodyassociated demyelination clinical imaging biological considerations diagnosis care summarythe field acquired cns neuroimmune demyelination children transforming progress assay development refinement diagnostic criteria increased biological insights provided advanced neuroimaging techniques highlevel evidence therapeutic efficacy biological agents redefining diagnosis care three distinct neuroimmune conditionsmultiple sclerosis myelinoligodendrocyte glycoprotein antibodyassociated disease mogad aquaporin4 antibodyassociated neuromyelitis optica spectrum disorder aqp4nmosd can now distinguished evidence humans animal models supporting distinct pathobiological disease mechanisms development highly effective therapies adultonset multiple sclerosis aqp4nmosd suppress relapse rate 90 motivated advocacy trials children however clinical trials challenging rarity conditions paediatric age group necessitating new approaches trial design including agebased trajectory modelling based phase 3 studies adults despite limitations future children adolescents living multiple sclerosis mogad aqp4nmosd far brighter years past will brighter still successful therapies promote remyelination enhance neuroprotection remediate cognitive deficits can accelerated,1.0
safety efficacy rituximab first second line treatment multiple sclerosis cohort study mult scler j exp transl clin 2021 jan 31 7 1 2055217320973049 doi 101177 2055217320973049 ecollection 2021 janmarabstractbackground rituximab increasingly used offlabel therapy multiple sclerosis ms data needed safety efficacy rituximab particularly cohorts de novo patients patients early therapy escalationobjective investigate safety efficacy offlabel treatment rituximab mscohort predominantly de novo patients therapy escalationmethods retrieved safety efficacy data norwegian msregistry biobank mspatients treated rituximab haukeland university hospital bergen norway four year periodresults 365 mspatients 320 relapsingremitting ms rrms 23 secondary progressive ms spms 22 primary progressive ms ppms overall annualized relapse rate arr 003 annualized drug discontinuation rate addr 005 neda3 achived 79 patients available data n351 sixtyone patients experienced infusionrelated adverse events two serious ctcae grade 34 eighteen patients experienced serious noninfusion related adverse events 16 infections infections n 34 93 ctcae grade 25 hypogammaglobulinemia n 19 52 neutropenia n 16 44 common noninfusionrelated adverse eventsconclusion rituximab safe highly efficient disease modifying therapy cohort mspatients however infections neutropenia need monitoredpmid33796328 pmcpmc7970692 doi101177 2055217320973049,0.0
urolithin ameliorates experimental autoimmune encephalomyelitis targeting aryl hydrocarbon receptor abstractbackgroundurolithin ura intestinal microbiota metabolic product ellagitannincontaining foods multiple biological activities however role autoimmune diseases largely unknown first time demonstrate therapeutic effect ura experimental autoimmune encephalomyelitis eae animal modelmethodstherapeutic effect evaluated via active passive eae animal model vivo function ura bone marrowderived dendritic cells bmdcs t cells microglia tested vitrofindingsoral ura 25 mg kg d suppressed disease progression prevention induction effector phases preclinical eae histological evaluation showed significantly fewer inflammatory cells decreased demyelination lower numbers m1type microglia activated dcs well reduced infiltrating th1 th17 cells present central nervous system cns uratreated group ura treatment 25 m inhibited activation bmdcs vitro restrained th17 cell differentiation t cell polarization conditions dccd4+ t cell coculture system moreover confirmed ura inhibited pathogenicity th17 cells adoptive eae mechanism ura action directly targeting aryl hydrocarbon receptor ahr modulating signaling pathwaysinterpretationcollectively study offers new evidence ura human microbial metabolite valuable use prospective therapeutic candidate autoimmune diseases,1.0
evaluation urinary tract infection following corticosteroid therapy patients multiple sclerosis exacerbation can j infect dis med microbiol 2021 jan 31 20216616763 doi 101155 2021 6616763 ecollection 2021abstractthe first treatment multiple sclerosis exacerbation usually shortterm intravenous methylprednisolone ivmp without regimen oral prednisone taper opt study aims evaluate effects ivmp opt comparison ivmp alone raising risk urinary tract infection uti posttreatment improvement urinary tract symptoms patients relapsingremitting multiple sclerosis doubleblind randomized clinical trial conducted 56 people multiple sclerosis relapse undergone methylprednisolone 5 days patients randomly split two groups oral prednisolone placebo tapering 20 days demographic data duration multiple sclerosis urinary tract symptoms expanded disability status scale edss score urine data analyzed incidence uti intervention control groups differ significantly p560 however improvement urinary tract symptoms intervention group significantly favorable control group p 0001 furthermore administering opt ivmp increase risk uti occurrence patients multiple sclerosis exacerbation urine analysis results show differences baseline corticosteroid tapering regimen due risk infection corticosteroids longer necessary urinary screening group patientspmid33603936 pmcpmc7870309 doi101155 2021 6616763,0.0
characterisation ms phenotypes across age span using novel data set integrating 34 clinical trials noms cohort age key contributor presentation abstractbackgroundthe oxford big data institute multiple sclerosis ms physicians novartis aim address unresolved questions ms novel comprehensive clinical trial data setobjectivethe objective study describe novartisoxford ms noms data set explore relationships age disease activity disease worsening across ms phenotypesmethodswe report key characteristics noms modelled ms lesion formation relapse frequency brain volume change disability worsening crosssectionally function patients baseline age using phase iii study data 8000 patients resultsnoms contains data 35 000 patients 200 000 brain images 10 000 patients 10years followup 1 focal disease activity highest paediatric patients decreases age 2 brain volume loss similar across age phenotypes 3 youngest patients lowest likelihood 25 disability worsening 2years risk higher 2575 older disabled progressive ms patients young patients benefit treatmentconclusionnoms will illuminate questions related ms characterisation progression prognosis age modulates relapse frequency thus phenotypic presentation ms disease worsening across phenotypes mediated age appears extent independent new focal inflammatory activity,0.0
cognitive impairment impacts exercise effects cognition multiple sclerosis front neurol 2021 jan 28 11619500 doi 103389 fneur2020619500 ecollection 2020abstractpurpose exercise training reveals high potential beneficially impact cognitive performance persons multiple sclerosis pwms research indicates highintensity interval training hiit potentially higher effects physical fitness cognition compared moderate continuous exercise study compares effects 3week hiit moderate continuous exercise training cognitive performance cardiorespiratory fitness pwms overall analysis ii investigates potential effects based baseline cognitive status subgroup analysis methods seventyfive pwms randomly assigned intervention hiit 5 15min intervals 95100 hrmax 3 week active control group cg 24 min continuous exercise 65 hrmax 3 week cognitive performance assessed pre postintervention brief international cognitive assessment ms bicams examine potential within time interaction time group effects overall analysis separate analyses covariance ancova conducted ii subgroup analysis participants divided two groups intact cognition impaired cognition 15 standard deviation sd compared healthy agematched norm data least one three tests bicams potential impacts cognitive status intervention investigated multivariate analyses variance manova results overall analysis revealed significant time effects processing speed verbal learning rel vo2peak rel power output timegroup interaction effect observed rel power output subgroup analysis indicated significant main effect cognition impaired cognition vs intact cognition subsequent posthoc analysis showed significant larger effects verbal learning pwms impaired cognition conclusion current results need confirmed powered randomized controlled trial cognitive performance primary endpoint eligibility based cognitive performance assessed prior study inclusionpmid33633658 pmcpmc7902024 doi103389 fneur2020619500,0.0
serum markers multiple sclerosis new approach optic neuritis typically manifests classical triad subacute unilateral vision loss periocular pain impaired colour vision first symptom multiple sclerosis ms 20 patients approximately half experiencing will develop ms however inflammatory diseases like neuromyelitis optica spectrum disease nmosd systemic lupus erythematosus sle sarcoidosis behchets disease infectious diseases like toxoplasmosis can also manifest 1 thus crucial importance improve diagnosis early ms number paraclinical measurements can assist providing correct diagnosis notably magnetic resonance imaging mri cerebrospinal fluid csf examination 1 specific biomarkers differential diagnosis nmosd developed patients tested specific antibodies aqp4igg mogigg serum cellbased essays however specific serological msbiomarkers exist present paper recently published ebiomedicine sadam colleagues 2 take new approach question increase diagnostic accuracy patients using mimotope variation analysis mva next generation phage display method detected two viral antibody epitopes possible new biomarkers msrisk epitopes gb cmv vca p18 ebv approach interesting several reasons first biomarkers detected seem improve diagnostic accuracy diagnosing ms early second point pathogenic mechanisms msdevelopment third serum biomarkers available blood much easier acquire mri lumbar puncture interestingly although authors used hypothesisfree approach findings point two common viral pathogens linked ms risk epidemiological studies higher titres epsteinbarr virus ebv epitopes consistently found increase risk developing ms 3 cytomegalovirus cmv seropositivity negatively associated ms risk 4 results current paper line previous findings sadam colleagues 2 identified clear negative association epitopes gb cmv risk developing ms negative association previous infections cmv risk ms reported one large swedish populationbased incident casecontrol study one small multiethnic us paediatric ms casecontrol study 5 recent study found however inconsistency across ethnic groups 6 indicating might causal association cmv ms consistent epidemiological results found second potential biomarker vca p18 ebv 3 6 authors suggested ms considered rare complication ebv infection 7 one large study early ms found 100 901 patients ebv positive controls reach 100 seropositvity investigated age cohorts 8 based findings authors suggested negative ebv serology alert clinicians consider diagnoses ms studies examined serum levels ebna1 marker previous ebv infection present paper epitope vca p18 ebv found associated risk ms 2 interestingly consistent results finish maternity cohort 7 study offspring mothers high vca igg pregnancy increased risk developing ms mechanism affect ms risk however still determined number precautions taken biomarkers can used clinical setting first results replicated larger independent cohorts preferentially prospective cohort studies examine benefit incorporating biomarkers riskevaluation scheme second biomarkers must evaluated different ethnic populations determine findings consistent across ethnic regional groups based previous trials especially cmv antibody responses seem determined ethnicity possibly causally linked risk ms third sensitivity specificity 75 know half patients will go develop ms diagnostic accuracy still far perfect potential biomarkers will probably need supplemented markers improve diagnostic accuracy summary present study adds growing number findings indicating immunological response herpes viruses cmv ebv linked risk developing ms reflect unique pathogenic mechanisms ms develops possibly improve future treatment diagnosis disease,0.0
synergic use botulinum toxin injection radial extracorporeal shockwave therapy multiple sclerosis spasticity acta biomed 2021 jan 28 92 1 e2021076 doi 1023750 abmv92i111101abstractbackground aim multiple sclerosis ms spasticity worsen patients quality life botulinum neurotoxin typea bonta extensively used focal spasticity frequently combined physical therapies radial extracorporeal shock waves resw already used association bonta considering loss efficacy adverse events determinants bonta treatment interruption study aimed evaluate possibility prolong bontas effect using resw ms focal spasticitymethods sixteen ms patients spasticity triceps surae muscles first subjected bonta therapy four months later 4 sections reswt patients evaluated 30 90 days end treatments using modified ashworth scale mas modified tardieu scale mts kinematic analysis passive active ankle rom results bonta determined significant reduction spasticity evaluated mas reduction positive effects 4months p005 mts highlighted efficacy 90 days injection p005 reswt decreased mas values end 30 days later treatment p001 mts values showed instead prolonged effect p001 bonta determined gain passive active ankle rom persisting along treatment peaking maximum value reswt p005 conclusions reswt can prolong bonta effect inducing significant reduction spasticity improvement passive active ankle rom ms patients use reswt following bonta injection useful avoid limitations prolong therapeutic effects bonta therapypmid33682833 doi1023750 abmv92i111101,0.0
rare case spinal neurosarcoidosis concomitant epidural lipomatosis case rep neurol med 2021 jan 28 20215952724 doi 101155 2021 5952724 ecollection 2021abstractintroduction spinal neurosarcoidosis rare disease can manifest myelopathy radiculopathy cauda equine syndrome spinal epidural lipomatosis also rare condition resulting overgrowth epidural fat tissue causing compressive myelopathy knowledge reports linking epidural lipomatosis spinal neurosarcoidosis case report describe case progressive myelitis presence concomitant spinal neurosarcoidosis epidural lipomatosis challenging diagnosis complete response treatment addressing diseases etiologies inflammatory nature share similar expression inflammatory factors tnf il1conclusion common inflammatory process involved two diseases might explain pathophysiological interconnection diseases may underlie concomitant development patient two diseases interconnected pathophysiological mechanism remains hypothesis will need investigationpmid33604089 pmcpmc7869444 doi101155 2021 5952724,0.0
effect action observation therapy rehabilitation neurologic musculoskeletal conditions systematic review arch rehabil res clin transl 2021 jan 27 3 1 100106 doi 101016 jarrct2021100106 ecollection 2021 marabstractobjective investigate effect action observation therapy aot rehabilitation neurologic musculoskeletal conditionsdata sources searches completed july 2020 electronic databases allied complementary medicine database via ovid sp cumulative index nursing allied health literature cochrane library embase medline physiotherapy evidence databasestudy selection randomized controlled trials comparing aot standard care assessed musculoskeletal amputee orthopedic neurologic dementia cerebral palsy multiple sclerosis parkinson disease stroke conditions included age limitations articles available englishdata extraction two reviewers independently screened titles abstracts full extracts studies eligibility assessed risk bias study using cochrane risk bias tool data extraction included participant characteristics intervention duration frequency typeresults effect aot different outcome measures oms referenced terms body structures functions activities participation environmental factors outlined international classification functioning disability health icf 3448 articles identified 36 articles 1405 patients met inclusion criteria seven 11 metaanalyses revealed significant effect intervention results presented using mean difference 95 ci best evidence synthesis used across oms strong evidence supports use aot rehabilitation individuals stroke parkinson disease moderate evidence supports aot rehabilitation populations orthopedic multiple sclerosis diagnoses however moderate evidence provided effect aot persons parkinson disease cerebral palsyconclusions review suggests aot advantageous rehabilitation certain conditions improving icf domains conclusions can drawn regarding treatment parameters heterogeneity intervention aot considerably less explored musculoskeletal conditionspmid33778479 pmcpmc7984987 doi101016 jarrct2021100106,0.0
impact autoimmune demyelinating brain disease sera pericyte survival noro psikiyatr ars 2021 jan 26 58 2 8386 doi 1029399 npa27350 ecollection 2021 junabstractintroduction multiple sclerosis ms autoimmune disease central nervous system cns characterized demyelination brain pericyte dysfunction might involved ms pathogenesis aim evaluate whether factors serum affect pericyte survivalmethod c57bl 6 female mice immunized myelin oligodendrocyte glycoprotein mog induce experimental autoimmune encephalomyelitis eae confirm animal model sera level antimog antibody mice plateletderived growth factorbb pdgfbb patients measured elisa human brain vascular pericytes hbvp cell lines incubated sera eae mice primer progressive ms ppms seconder progressive ms spms relapsingremitting ms rrms patients viability hbvp measured annexin vfitc propidium iodide staining flow cytometryresults annexin vfitc propidium iodide staining flow cytometry showed increased ratios early apoptosis decreased survival following incubation sera eae progressive ms levels plateletderived growth factorbb identical serum cerebrospinal fluids patients different forms msconclusion results suggest serum factors might contribute progressive ms pathogenesis via pericyte dysfunctionpmid34188587 pmcpmc8214738 doi1029399 npa27350,1.0
identification two highly antigenic epitope markers predicting multiple sclerosis optic neuritis patients abstractbackgroundoptic neuritis can occur isolated episode will develop multiple sclerosis ms chronic autoimmune disease predicts progression ms remains poorly understoodmethodswe characterised antibody epitope repertoire three independent clinical cohorts discovery n62 validation n20 external cohort n421 using mimotope variation analysis mva next generation phage display technology identify epitopes associate prognosis onfindingswe observed distinct epitope profiles ms controls whereas epitope repertoires sera csf highly similar two unique highly immunogenic epitopes b detected subjects progressing ms epitopes b strongly associated herpesviral antigens vca p18 epsteinbarr virus ebv gb cytomegalovirus cmv roc addressed 75 ms subjects onset correctly 75 sensitivity 7422 specificity based twoepitope biomarker analysisinterpretationthis first report epitope diagnostics ms employing unbiased strategy mva identification novel immunological features diseasefundingthe estonian ministry education estonian research council prg573 prg805 psg691 h2020mscarise2016 sztest h2020nmbp2017 panbiora helsinki university hospital mary georg c ehrnrooth finnish eye sigrid juslius magnus ehrnrooth foundations,0.0
prevalence radiologically isolated syndrome pediatric populationbased cohort longitudinal description rare diagnosis abstractbackgroundradiologically isolated syndrome ris typified multiple sclerosis ms like lesions imaging without clinical ms symptoms prevalence pediatric ris largely unknownobjectivethe objective study provide estimated ris prevalence populationbased cohort childrenmethodswe used data generation r study identify childhood ris prevalenceresultsin 5238 participants one ris case identified prevalence 002 95 confidence interval ci 000011 62month followup imaging examinations showed accrual new focal demyelinating lesions however clinical ms symptoms occurredconclusionsthis study shows occurrence ris children general population rare,1.0
bioequivalence intramuscular subcutaneous peginterferon beta1a results phase openlabel crossover study healthy volunteers ther adv neurol disord 2021 jan 22 141756286420975227 doi 101177 1756286420975227 ecollection 2021abstractbackground peginterferon beta1a administered every 2 weeks via subcutaneous sc injection approved treat adult patients relapsingremitting multiple sclerosis rrms relapsing forms multiple sclerosis rms however associated injection site reactions isrs can lead treatment discontinuation prior studies interferon beta1a reported lower frequency isrs intramuscular im administration sc administration im administration peginterferon beta1a may therefore represent useful alternative treatment optionmethods phase openlabel twoperiod crossover study randomized healthy volunteers receive single dose peginterferon beta1a 125 mcg administered im followed single 125 mcg dose administered sc 28day washout vice versa blood samples collected 504 h post dose determine pharmacokinetic pk pharmacodynamic pd profiles primary endpoint assessment bioequivalence based maximum serum concentration cmax area curve time zero extrapolated infinity aucinf pk parameters well pd serum neopterin safety profiles also evaluatedresults study enrolled 136 participants bioequivalence im sc peginterferon beta1a established cmax least squares ls mean im sc ratio 1083 90 confidence interval ci 09751203 aucinf ls mean im sc ratio 1089 90 ci 10201162 pk pd parameters similar administration routes although moderate high intersubject variability observed im sc safety profiles generally balanced im sc administration isrs occurred lower frequency im 144 95 ci 8892156 sc 321 95 ci 24294070 administration p 00005 conclusions results demonstrate bioequivalence peginterferon beta1a im sc support consideration im injection peginterferon beta1a viable treatment option patients rrms rmspmid33628334 pmcpmc7883310 doi101177 1756286420975227,0.0
csf extracellular vesicles risk disease activity first demyelinating event abstractbackgroundextracellular vesicles evs recently described mechanism cell communication released activated microglial cells macrophages candidate biomarker diseases characterized chronic inflammatory process multiple sclerosis ms methodswe explored cerebrospinal fluid extracellular vesicle csf ev myeloid origin mevs cytokine chemokine levels patients clinically isolated syndrome cis resultswe found csf mevs significantly higher cis patients controls inversely correlated csf ccl2 levels mevs level significantly associated shorter time evidence disease activity hazard ratio 101 95 confidence interval 100102 p001 independently known prognostic markersconclusionafter first demyelinating event csf evs may improve risk stratification patients allow targeted intervention strategies,1.0
systemic sclerosis current state survival lung transplantation cureus 2021 jan 20 13 1 e12797 doi 107759 cureus12797abstractsystemic sclerosis ssc autoimmune disorder characterized involvement skin internal organs introduction angiotensinconverting enzyme inhibitors aceis scleroderma renal crisis src longer considered leading cause death affected patients fact pulmonary manifestations interstitial lung disease ild pulmonary arterial hypertension pah currently major cause death patients ssc historically many centers reluctant offer lung transplantation patients ssc due multiple extrapulmonary manifestations assumption poor posttransplant survival purpose review highlight recent advances evaluation management patients pulmonary manifestations ssc also engage systematic literature review assess available data survival patients ssc lung transplantationpmid33628666 pmcpmc7893677 doi107759 cureus12797,0.0
exploratory study diet childhood young adulthood adultonset multiple sclerosis abstractthere little evidence role diet childhood adolescence multiple sclerosis ms adulthood ms sunshine study recruited adults recentonset ms n602 matched controls n653 84 provided dietary recall specific ages childhood young adulthood 610 1115 1620years used logistic regression test associations agespecific diet casecontrol status consumption fruit ages yoghurt ages legumes 1115years associated lower probability adultonset ms p005 results suggest healthy dietary habits childhood young adulthood may reduce ms risk,0.0
recent advances future directions use optical coherence tomography neuroophthalmology taiwan j ophthalmol 2021 jan 20 11 1 315 doi 104103 tjotjo_76_20 ecollection 2021 janmarabstractoptical coherence tomography oct noninvasive imaging technique used qualitatively quantitatively analyze various layers retina oct retinal nerve fiber layer rnfl ganglion cellinner plexiform layer gcipl particularly useful neuroophthalmology evaluation patients optic neuropathies retrochiasmal visual pathway disorders oct allows objective quantification edema atrophy rnfl gcipl may evident obvious clinical signs visual dysfunction develop enhanced depth imaging oct allows visualization deep structures optic nerve emerged gold standard detection optic disc drusen evaluation compressive optic neuropathies oct rnfl gcipl thicknesses established important visual prognostic factor increasing evidence inclusion oct part diagnostic criteria multiple sclerosis ms increases sensitivity moreover oct rnfl gcipl may helpful early detection monitoring treatment conditions ms alzheimers disease oct important aspect neuroophthalmologic assessment use likely increase moving forwardpmid33767951 pmcpmc7971436 doi104103 tjotjo_76_20,0.0
disruption conscious access psychosis associated altered structural brain connectivity according global neuronal workspace gnw theory conscious access relies longdistance cerebral connectivity allow global neuronal ignition coding conscious content patients schizophrenia bipolar disorder alterations cerebral connectivity increased threshold conscious perception reported implications abnormal structural connectivity disrupted conscious access relationship two deficits psychopathology remain unclear aim study determine extent structural connectivity correlated consciousness threshold particularly psychosis used visual masking paradigm measure consciousness threshold diffusion mri tractography assess structural connectivity 97 humans either sex varying degrees psychosis healthy control subjects n46 schizophrenia patients n25 bipolar disorder patients n17 without n9 history psychosis patients psychosis schizophrenia bipolar disorder psychotic features elevated masking threshold compared control subjects bipolar disorder patients without psychotic features masking threshold correlated negatively mean general fractional anisotropy white matter tracts exclusively within gnw network inferior frontaloccipital fasciculus cingulum corpus callosum mediation analysis demonstrated alterations longdistance connectivity associated increased masking threshold turn linked psychotic symptoms findings support hypothesis longdistance structural connectivity within gnw plays crucial role conscious access conscious access may mediate association impaired structural connectivity psychosis,0.0
effect neuromuscular exercises strength proprioceptive receptors balance females multiple sclerosis int j prev med 2021 jan 19 125 doi 104103 ijpvmijpvm_525_18 ecollection 2021abstractbackground multiple sclerosis ms third common cause adult neurologic disabilities aim study determine effect 8 weeks neuromuscular exercises strength proprioceptive receptors balance women msmethods randomized controlled trial study 20 female volunteers relapsingremitting ms randomly assigned experimental group n 10 control group n 10 maximum muscular strength knee extensor flexor muscles knee joint proprioceptive error biodex balance berg balance scale measured baseline 8 weeks neuromuscular exercise data analyzed using paired ttest independent ttestresults results showed significant improvement p 005 quadriceps strength hamstring strength proprioceptive receptor error balance experimental group control group significant difference evident experimental control groups terms strength balance proprioceptive receptor error p 005 conclusions neuromuscular exercise training effective improving balance strength reducing proprioceptive error people ms recommended modalities patientspmid34084302 pmcpmc8106275 doi104103 ijpvmijpvm_525_18,0.0
balo#39 s concentric sclerosis mimicking tumor magnetic resonance imaging young patient clin med insights case rep 2021 jan 19 141179547621989673 doi 101177 1179547621989673 ecollection 2021abstractbalos concentric sclerosis bcs rare demyelinating disease known multiple sclerosis ms lesion type iii disease white matter brain characterized round lesion variable concentric myelinated demyelinated layers appearing onion bulb present case bcs discuss imaging findings management strategies disease 26yold male developed headache weakness numbness limbs magnetic resonance imaging mri showed concentric lamellar like demyelinating lesions subcortical regions patients neurological symptoms consistent mri findingspmid33786003 pmcpmc7960892 doi101177 1179547621989673,1.0
two case reports acquired haemophilia complications alemtuzumab treatment multiple sclerosis bmj neurol open 2021 jan 18 3 1 e000095 doi 101136 bmjno2020000095 ecollection 2021abstractobjective describe case histories two patients developed acquired haemophilia following treatment alemtuzumab multiple sclerosisresults two patients 48yearold woman 31yearold woman developed acquired haemophilia 21 months second doses alemtuzumab presented spontaneous bruising second case reported menorrhagia one patient required treatment control bleeding patients responded treatment prednisolone cyclophosphamide eliminate inhibitorconclusions acquired haemophilia rare complication following treatment alemtuzumab activated partial thromboplastin time prothrombin time performed cases abnormal bleeding platelet count normal facilitate timely diagnosis prevention major bleeding complicationspmid33681807 pmcpmc7871705 doi101136 bmjno2020000095,0.0
cobalt deficiency cattle impact production two outbreaks cobalt deficiency beef cattle diagnosed midwestern brazil discuss clinical epidemiological pathological features therapeutic measures impact aspects production system associated outbreaks occurring outbreaks two farms extensive cattle raisingsystem state mato grosso sul seven affected cattle euthanized necropsied tissues histopathology microelements dosage secured farm 3100 cattle ages got sick 396 died farm b 148 affected 110 died farms cattle fed mineral supplement main clinical signs weight loss weakness even though good supply forage available paddocks many cattle stop grazing chew tree barks wood chips fence posts bones addition deaths compromised growth reproductive rates fell sharply necropsied cattle thin rough hair coat pale mucous membranes liver diffusely orange showed lobular pattern bone marrow gelatinous diffusely yellow histological changes included hemosiderosis liver spleen hepatocellular vacuolar degeneration myeloid erythroid hypoplasia bone marrow white matter four cattles brains myelin sheath markedly distended spongy degeneration proliferative parasitic abomasitis observed three cattle presumptive diagnosis based association clinical picture necropsy findings ruling possible causes diagnosis confirmed favorable response treatment cobalt vitamin b12 orally mineral supplementation,1.0
depression anxiety disorders patients multiple sclerosis association neurodegeneration neurofilaments increasing evidence neurofilament light chain nfl can considered biomarker neuroaxonal damage polypeptide can released cerebrospinal fluid csf blood can quantified concentration nfl elevated patients multiple sclerosis ms psychiatric disorders aimed investigate nfl levels csf treated ms patients relationship depression anxiety study involved three groups control group individuals without inflammation relapseremitting multiple sclerosis rrms untreated group rrmsfingo group rrms patients treated fingolimod ms disability assessed expanded disability status scale depression anxiety evaluated neuropsychologist using hospital anxiety depression scale beck depression inventoryii beck anxiety inventory individual csf samples collected measure nfl levels results statistical analysis levels nfl csf control subjects rrmsuntreated patients rrmsfingo patients significant relationship depression anxiety rrmsfingo patients nfl levels statistically significant conclusion ms events anxiety depression appear contribute onset clinical relapses subclinical cases neurodegeneration,0.0
chronic pharmacological increase neuronal activity improves sensorymotor dysfunction spinal muscular atrophy mice dysfunction neuronal circuits important determinant neurodegenerative diseases synaptic dysfunction death intrinsic activity neurons thought contribute demise normal behavior disease state however interplay major pathogenic events disease progression poorly understood spinal muscular atrophy sma neurodegenerative disease caused deficiency ubiquitously expressed protein smn characterized motor neuron death skeletal muscle atrophy well dysfunction loss central peripheral excitatory synapses disease hallmarks result overall reduction neuronal activity spinal sensorymotor circuit show increasing neuronal activity chronic treatment fdaapproved potassium channel blocker 4aminopyridine 4ap improves motor behavior sexes severe mouse model sma 4ap restores neurotransmission number proprioceptive synapses neuromuscular junctions nmjs effects motor neuron death addition 4ap treatment pharmacological inhibition p53dependent motor neuron death results additive effects leading full correction sensorymotor circuit pathology enhanced phenotypic benefit sma mice vivo study reveals 4apinduced increase neuronal activity restores synaptic connectivity function sensorymotor circuit improve sma motor phenotypesignificance statement spinal muscular atrophy sma neurodegenerative disease characterized synaptic loss motor neuron death reduced neuronal activity spinal sensorymotor circuits however whether parallel dependent events unclear show longterm increase neuronal activity fdaapproved drug 4aminopyridine 4ap rescues number function central peripheral synapses sma mouse model resulting improvement sensorymotor circuit motor behavior combinatorial treatment pharmacological inhibition p53 responsible motor neuron death 4ap results additive beneficial effects sensorymotor circuit sma thus neuronal activity restores synaptic connections improves significantly severe sma phenotype,0.0
oligoclonal igm bands cerebrospinal fluid patients relapsing ms inform longterm ms disability abstractbackgroundprognostic markers needed guide multiple sclerosis ms management context large availability diseasemodifying drugs dmds objectiveto investigate role cerebrospinal fluid csf markers inform longterm ms outcomesmethodsdemographic features igm index oligoclonal igm bands ocmb lipidspecific ocmb csf neurofilament light chain protein levels expanded disability status scale edss relapses dmd use study period peripapillary retinal nerve fiber layer prnfl ganglion cell plus inner plexiform layer gcipl thicknesses nonoptic neuritis eyes end followup collected relapsing ms rms patients csf obtained 2years ms onset prospectively followed hospital clinic barcelona assessed associations csf markers ms outcomes using multivariable modelsresultsa total 89 patients 71 females median 329years age followed median 96years included ocmb associated 33 increase annualized relapse rate arr p 006 higher odds highefficacy dmds use 48 95 ci 15 161 thinner prnfl 44 95 ci 86 02 gcipl 29 95 ci 59 +005 higher rates edss 30 hr 44 95 ci 16 118 edss 40 hr 54 95 ci 11 271 overall associations found csf markersconclusionthe presence ocmb associated unfavorable longterm outcomes ocmb determined rms inform longterm prognosis,0.0
alemtuzumab multiple sclerosis retrospective analysis occult hemorrhagic mri lesions risk factors eur j neurol 2021 aug 9 doi 101111 ene15054 online ahead printabstractbackground alemtuzumab monoclonal cd52 antibody highefficacy diseasemodifyingtherapy relapsingremitting multiple sclerosis rrms recently intracerebral hemorrhage ich reported possible treatment related adverse event arterial hypertension infusion suggested potential cause although platelet endothelial dysfunction may also contribute study aimed screen occult hemorrhagic cerebral lesions alemtuzumab treatment elucidate risk factorsmethods included 30 rrms patients received alemtuzumab treatment ghent university hospital sintjan bruges hospital retrospective data concerning vital signs adverse effects thrombocyte levels treatment collected occurrence occult intracranial hemorrhagic lesions assessed mri susceptibilityweighted imaging swi results mean systolic blood pressure sbp morning noon evening 120 mmhg first administration sd338 114 mmhg second administration sd440 n13 significant increase sbp comparing morning noon evening per day significant difference daily mean sbp consecutive administration days thrombocyte count treatment cycles ranged 107x109 l 398x109 l mean absolute reduction 593x109 l sd5065 mean relative reduction 250 sd1284 n20 patients suffered ich swi show cerebral microbleeds hemorrhagic lesions posttreatment n23 conclusions patient population alemtuzumab treatment associated arterial hypertension ich occult microbleeds possible differences administration regimen ambulatory versus inhospitalsetting patient population cardiovascular risk might explain increased risk different populationspmid34374173 doi101111 ene15054,0.0
association peripapillary hyperreflective ovoid masslike structures disease duration primary progressive multiple sclerosis eur j neurol 2021 aug 9 doi 101111 ene15056 online ahead printabstractbackground peripapillary hyperreflective ovoid masslike structures phoms novel finding retinal optical coherence tomography oct patients multiple sclerosis ms date data occurrence phoms early ms aim study investigate frequency phoms patients firstly diagnosed early relapsing remitting ms rrms search associations phoms disease patterns different ms subtypesmethods crosssectional analysis two different cohorts cohort 1 consisting early rrms patients n349 cohort 2 consisting patients primary progressive ms ppms n66 rrms n65 results phoms detected 183 patients early rrms occurrence phoms associated age disease duration disability investigating clinical patterns occurrence phoms cohort 2 saw association phoms higher expanded disability status scale edss measures phoms 49 3761 phoms 35 3053 p003 longer disease durations phoms 65 years 19110 phoms 10 years 0040 p00007 patients ppms rrms pvalue adjustment disease duration appeared relevant 016 p006 conclusion found phoms 18 patients early ms presence phoms might associated disease progression ppms rrms suggesting phoms might embedded neurodegenerative processespmid34374178 doi101111 ene15056,0.0
reactive balance responses trip slip gait people multiple sclerosis clin biomech bristol avon 2021 oct 9 90105511 doi 101016 jclinbiomech2021105511 online ahead printabstractbackground examine reactive balance responses trip slip gait people multiple sclerosis ms methods crosssectional laboratory study involved 29 participants ms 506 134 years 29 genderandagedmatched healthy controls 509 192 years falls following induced trip slip along 10 m walkway approach eg gait speed step length foot contact angle recovery strategies eg response time extrapolated centre mass position margin stability compared two groupsfindings rate falls significantly higher participants ms relative healthy controls rate ratio282 95 confidence interval ci 142 561 participants ms also experienced trip falls odds ratio 390 95 ci116 1308 slip falls or627 95 ci195 2022 heathy controls participants ms significantly slower gait speed step length cadence foot contact angle approach p 005 following slips participants ms significantly greater stance limb knee flexion p 005 suggesting inadequate lower limb support recover balance postslip following trips participants ms significantly delayed response initiation lower toe clearance shorter step length greater trunk sway p 005 fewer participants ms showed hopping response clear obstacle p 005 interpretation multiple sclerosis impairs reactive balance responses trip slip associated reduced lower limb function delayed postural responses neurorehabilitation targeting reactive balance may facilitate fall prevention people multiple sclerosispmid34710843 doi101016 jclinbiomech2021105511,0.0
common rare variant association analyses amyotrophic lateral sclerosis identify 15 risk loci distinct genetic architectures neuronspecific biology nat genet 2021 dec 53 12 16361648 doi 101038 s41588021009731 epub 2021 dec 6abstractamyotrophic lateral sclerosis als fatal neurodegenerative disease lifetime risk one 350 people unmet need diseasemodifying therapies conducted crossancestry genomewide association study gwas including 29 612 patients als 122 656 controls identified 15 risk loci combined 8 953 individuals wholegenome sequencing 6 538 patients 2 415 controls large cortexderived expression quantitative trait locus eqtl dataset metabrain analyses revealed locusspecific genetic architectures prioritized genes either rare variants short tandem repeats regulatory effects alsassociated risk loci shared multiple traits within neurodegenerative spectrum distinct enrichment patterns across brain regions cell types environmental lifestyle risk factors obtained literature mendelian randomization analyses indicated causal role high cholesterol levels combination alsassociated signals reveals role perturbations vesiclemediated transport autophagy provides evidence cellautonomous disease initiation glutamatergic neuronspmid34873335 doi101038 s41588021009731,0.0
calciumphosphate homeostasis secondary progressive multiple sclerosis patients mitoxantrone therapy neurol res 2021 jul 916 doi 101080 0161641220211949683 online ahead printabstractobjectives assess calciumphosphate parameters spms patients treated mitoxantrone mtx methods thirty eight spms patients eligible mtx therapy department neurology zabrze poland enrolled prospective study march 2016 november 2019 parameters serum calciumphosphate metabolism neurological status according expanded disability status scale edss assessed patients hypovitaminosis d vitamin d vitd supplementation introduced 4000 iu day 1 month later 2000 iu day results patients women 5789 mean age years 5611 774 median time diagnosis inclusion day id 750 4001400 years due vitd supplementation increase serum vitd observed study 8421 patients presented hypovitaminosis d mtx treatment compared 4737 treatment mtx therapy none patients underwent surgical repair fracture compared 4211 patients mtx treatment p 001 discussion deficiency vitd observed baseline spms patients eligible mtx therapy due adverse reactions mtx treatment therapy requires patient compliance cautious drug administration monitoring therapypmid34240684 doi101080 0161641220211949683,0.0
multiple sclerosis neuromyelitis optica spectrum disorder testing treatment availability latin america neurol res 2021 jul 916 doi 101080 0161641220211949686 online ahead printabstractbackground objective study describe availability diagnostic tests treatment ms nmosd latin america latam methods survey instrument used sample physicians latam countries goal survey understand availability 1 imaging tests diagnosing ms nmosd barriers 2 diagnostic laboratory tests diagnosing ms nmosd barriers 3 treatments ms nmosd acute chronic phases diseaseresults responses received 80 physicians aqp4ab test available 54 countries mogab test 42 countries available use high doses intravenous methylprednisolone oral steroids plasmapheresis intravenous immunoglobulins relapses nmosd 93 countries able use azathioprine mycophenolate mofetil 87 rituximab ms 93 countries available ifn beta 69 glatiramer acetate 75 teriflunomide 93 fingolimod 69 dimethylfumarate 75 cladribine 69 natalizumab 93 ocrelizumab 81 alemtuzumab common challenge barrier identified cost medicationsconclusion present study allows understanding delivery care ms nmosd regionpmid34240685 doi101080 0161641220211949686,0.0
multiple sclerosis focus sides auto antibody neural regen res 2021 dec 16 12 24222424 doi 104103 16735374313045no abstractpmid33907027 doi104103 16735374313045,0.0
epileptogenic zone children tuberous sclerosis complex characterized prominent features focal cortical dysplasia epilepsia open 2021 jul 30 doi 101002 epi412529 online ahead printabstractobjective patients tuberous sclerosis complex tsc present drugresistant epilepsy 60 cases evaluation epilepsy surgery may warranted correct delineation epileptogenic zone ez amongst multiple dysplastic lesions mri represents challenging step presurgical evaluationmethods two experienced neuroradiologists evaluated pre postsurgical mris 28 epilepsy surgery patients tsc assessing characteristics tubers cysts calcifications focal cortical dysplasia fcd resembling lesions utilizing multiple metrics compared mri features ez defined resected area tsc patients achieved seizurefreedom two years epilepsy surgery features brain areas using combinatorial analysis identified combinations dysplastic features frequently observed epileptogenic zone tsc patientsresults tsc associated dysplastic features frequently observed ez brain areas increased cortical thickness greywhite matter blurring transmantle sign calcifications tubers kendals tau 035 025 027 026 023 respectively p value 0001 single feature reliably independently indicate ez patients conversely ez indicated presence combination three following features tubers transmantle sign increased cortical thickness calcifications largest fcdaffected area largest fcdaffected area emerged reliable indicator ez combined either calcifications tuberssignificance epileptogenic zone tsc patients harbors multiple dysplastic features consistent focal cortical dysplasia specific combination features can indicate ez aid presurgical mri evaluation epilepsy surgery candidates tscpmid34328682 doi101002 epi412529,0.0
diseasemodifying therapy usage patients multiple sclerosis france 6year populationbased study rev neurol paris 2021 jul 9s00353787 21 005877 doi 101016 jneurol202104006 online ahead printabstractbackground data regarding use diseasemodifying therapies dmts multiple sclerosis ms comes clinical series regional databases risk recruitment bias french health administrative data offers significant advantage extensive regards ms population coverage dmt prescriptionsobjectives describe patterns dmts usage level entire french population ms patients 2010 2015methods ms patients identified 6year study period via french national health data system covering 97 general population characteristics patients received least one treatment compared never received treatment indicated period state sequence analysis performed study longitudinal way ms patients started dmts 2010 classify groups similar therapeutic patterns dmts categorized firstline secondline offlabel use included untreated periods least six months groups obtained described compared using multinomial logistic regressionresults total 112 415 patients ms identified 540 received least one dmt 6 years probability treated significantly decreased age comorbidities physical limitations appeared frequent treated patients treated patients significant differences also found two groups regarding use healthcare services hospitalizations visits general practitioner neurologist nurse based 6year therapeutic sequences fourcluster typology obtained 4 474 patients started dmt 2010 first group consisted half patients 570 mainly used firstline dmts second group 131 represented patients secondline dmts whereas third group 73 comprised offlabel users last group 226 composed ms patients received minimal treatments classification one groups associated patients age longterm disease status pregnancy occurrence estimated level disability levels care visits neurologist nurse physiotherapist hospital rehabilitation stays occurrence deathconclusions exhaustive populationbased dataset french national health data system gave opportunity provide detailed description regarding use dmts ms national level innovative method state sequence analysis allowed obtaining four homogeneous groups patients among thousands longitudinal therapeutic sequences predominant place firstline treatments confirmed even type firstline treatments probably changed since 2015pmid34253346 doi101016 jneurol202104006,0.0
pilot study enhancing cardiorespiratory exercise response people advanced multiple sclerosis hybrid functional electrical stimulation arch phys med rehabil 2021 jul 17s00039993 21 005049 doi 101016 japmr202107001 online ahead printabstractobjective investigate pilot study acute cardiorespiratory responses functional electrical stimulation fes cycling arm cranking exercise ace combination ace fes cycling hybrid fes cycling people advanced multiple sclerosis ms provide preliminary guidance effective aerobic exercise prescriptiondesign acute repeated measuressetting laboratory settingparticipants inclusion criteria diagnosis ms expanded disability status scale edss 60 85 included 9 participants 7 female age 547 88 years edss 70 72 intervention participants assessed three different exercise modalities fes cycling ace hybrid fes cycling 40 60 80 100 modespecific peak workloadmain outcome measures oxygen consumption vo2 heart rate hr measured workloadresults hybrid fes cycling evoked significantly higher vo2relative mlkg1min1 hr bpm workloads compared ace fes cycling 100 workload hr hybrid fes cycling 125 113148 bpm significantly higher ace 99 95119 bpm p0008 fes cycling 94 79100 bpm p0008 similarly 100 workload vo2relative hybrid fes cycling 118 76176 mlkg1min1 significantly higher ace 89 53125 mlkg1min1 p0012 fes cycling 68 4192 mlkg1min1 p0012 conclusions pilot study showed hybrid fes cycling can elicit greater cardiorespiratory response compared ace fes cycling people advanced ms thus hybrid fes cycling might provide potent enough stimulus induce clinically relevant changes cardiorespiratory fitness training studies warranted document magnitude sustainability aerobic capacity adaptations hybrid fes cycling associated health outcomes advanced mspmid34283994 doi101016 japmr202107001,0.0
major fungal infections can initiate severe autoimmune diseases microb pathog 2021 sep 16105200 doi 101016 jmicpath2021105200 online ahead printabstractseveral autoimmune diseases long linked viral bacterial infections contrast possibility fungal infections causing autoimmune diseases received almost attention however major fungal infections can cause severe autoimmune diseases decreasing treg cells increasing production interleukin23 cd4 th17 t cells interleukin17 cytokines including interleukin22 several factors can cause fungal infections including antibiotic usage bacterial fungal populations compete mammalian oropharyngeal respiratory gastrointestinal genitourinary tracts antibiotic usage decreases bacteria thereby favors fungal populations bacterial populations leads explanatory hypothesis pathogenesis severe autoimmune diseases major fungal infections increase fungal populations individuals susceptible major fungal infections can also explain higher incidence autoimmune diseases cd4 th17 t cells certain interleukins can one path pathogenesis major fungal infections increased incidences major autoimmune diseases including type 1 diabetes multiple sclerosis various types arthritispmid34537272 doi101016 jmicpath2021105200,0.0
tofacitinib enhances remyelination improves myelin integrity cuprizoneinduced mice immunopharmacol immunotoxicol 2021 oct 719 doi 101080 0892397320211986063 online ahead printabstractaim demyelination subsequent remyelination wellknown mechanisms multiple sclerosis ms pathology current research mainly focused preventing demyelination regulating peripheral immune system protect damage central nervous system however information another essential mechanism remyelination balance immune response within central nervous systems boundaries still limitedmaterials methods study tried demonstrate effect recently introduced janus kinase jak signal transducer activator transcription stat inhibitor tofacitinib remyelinationdemyelination induced 6week cuprizone administration followed 2week tofacitinib 10 30 100 mg kg treatmentresults functional level tofacitinib improved cuprizoneinduced decline motor coordination muscle strength assessed rotarod hanging wire tests tofacitinib also showed antiinflammatory effect alleviating cuprizoneinduced increase central levels interferon ifn interleukin il 6 il1 tumor necrosis alpha tnf furthermore tofacitinib also suppressed cuprizoneinduced increase matrix metalloproteinases mmp 9 mmp2 levels additionally cuprizoneinduced loss myelin integrity myelin basic protein expression inhibited tofacitinib molecular level also assessed phosphorylation stat3 stat5 data indicates tofacitinib suppressed cuprizoneinduced phosphorylation proteinsconclusion study highlights jak stat inhibition provides beneficial effects remyelination via inhibition inflammatory cascadepmid34618622 doi101080 0892397320211986063,1.0
role transformative potential il19 atherosclerosis cytokine growth factor rev 2021 sep 21s13596101 21 00068x doi 101016 jcytogfr202109001 online ahead printabstractatherosclerotic cardiovascular disease leading cause death worldwide traditionally il19 thought expressed immune cells studies revealed il19 also expressed multiple atherosclerotic plaque cell types normal arteries humans mice il19 reduces development atherosclerosis via multiple mechanisms including balancing cholesterol metabolism enhancing th2 immune cell polarization reducing inflammatory response reducing proliferation migration chemotaxis vascular smooth muscle cells vsmcs clinical animal studies primarily aimed achieve regression stabilization atherosclerotic plaques regression particular indicating good drug response antiatherosclerotic drugs current clinical use including atorvastatin alirocumab target hyperlipidemia several drugs also investigated clinical trials antiinflammatory agents development agents terminated canakinumab darapladib varespladib losmapimod atreleuton setileuton pf04191834 veliapon methotrexate others remain development ziltivekimab tocilizumab somalix ifm2427 anakinra mesenchymal stem cells mscs colchicine everolimus allopurinol montelukast tested drugs shown limited ability reverse atherosclerosis animal studies interestingly recombinant il19 ril19 shown reduce atherosclerosis development time dosedependent manner low dose ril19 1 ng g day reduced aortic arch root plaque areas 701 321 respectively ldlr mice 10 ng g day ril19 completely eliminated atherosclerotic plaques sex differences effects ril19 atherosclerotic mice thus lowdose ril19 effective antiatherosclerotic agent addition efficacy intimal hyperplasia spinal cord injury stroke multiple sclerosis propose il19 promising biomarker target diagnosis treatment atherosclerosis review considers role mechanism action il19 atherosclerosis discusses whether il19 potential therapeutic target conditionpmid34600839 doi101016 jcytogfr202109001,0.0
matter atrophy differential impact brain spine damage disability worsening multiple sclerosis j neurol 2021 may 3 doi 101007 s00415021105769 online ahead printabstractas atrophy represents relevant driver progression multiple sclerosis ms investigated impact different patterns brain spinal cord atrophy disability worsening ms acquired clinical mri data 90 patients relapsingremitting ms 24 healthy controls hc clinical progression followup mean 37 years defined according expanded disability status scaleplus brain spinal cord volumes computed mri brain scans normalizing participants brain spine volume mean hc zscore cutoffs applied separate pathologically atrophic normal brain spine volumes accepting 25 error probability accordingly ms patients classified four groups group brain spinal cord atrophy n 40 group ii brain atrophy spinal cord atrophy n 11 group iii brain atrophy spinal cord atrophy n 32 group iv brain spinal cord atrophy n 7 patients groups showed significantly lower brain volume hc p 00001 group iii iv showed lower spine volume hc p 00001 higher brain lesion load identified group ii p 0049 group iv p 0023 vs group group iv p 0048 vs group iii spinal cord atrophy 375 p 0018 brain + spinal cord atrophy 571 p 0046 significant predictors disability progression presence concomitant brain spinal cord atrophy strongest correlate progression time isolated spinal cord atrophy exerts similar effect confirming leading role spinal cord atrophy determination motor disabilitypmid33942160 doi101007 s00415021105769,0.0
antagonizing astrocytic platelet activating factor receptorneuroinflammation total flavone epimedium response cuprizone demyelination int immunopharmacol 2021 oct 1 101 pt 108181 doi 101016 jintimp2021108181 online ahead printabstractdemyelinating diseases central nervous system characterized recurrent demyelination progressive neurodegeneration clinical drugs targeting myelin regeneration improving functional disability treatment multiple sclerosis total flavone epimedium tfe main active components epimedium exhibits beneficial biological activities treatment diseases report treatment demyelinating disorder purpose study explore therapeutic potential possible mechanism tfe treatment demyelination results showed tfe efficiently improved behavioural performance histological demyelination cuprizone cpz induced demyelinating model terms action tfe increased astrocytes enrichment corpus callosum striatum cortex promoted astrocytes express neurotrophic factors furthermore expression plateletactivating factor receptor pafr astrocytes induced cpz feeding lps stimulation accompanied increase inflammatory cytokines tnf il6 il1 tfe declined expression pafr inhibited inflammatory response time tfe also antagonized pafr activation inflammatory response triggered paf confirmed tfe new pafr antagonist inhibited astrocytederived inflammatory response antagonizing pafrneuroinflammation axis thus contributing myelin protection regenerationpmid34607229 doi101016 jintimp2021108181,1.0
cervical cord myelin abnormality associated clinical disability multiple sclerosis mult scler 2021 mar 2213524585211001780 doi 101177 13524585211001780 online ahead printabstractbackground myelin water imaging mwi recently optimized provide quantitative vivo measurement spinal cord myelin critically involved multiple sclerosis ms disabilityobjective assess cervical cord myelin measurements relapsingremitting multiple sclerosis rrms progressive multiple sclerosis progms participants evaluate correlation myelin measures clinical disabilitymethods used mwi data 35 rrms 30 progms 28 healthy control hc participants collected cord level c2 c3 3 t magnetic resonance imaging mri scanner myelin heterogeneity index mhi measurement myelin variability calculated whole cervical cord global white matter dorsal column lateral ventral funiculi correlations assessed mhi expanded disability status scale edss 9hole peg test 9hpt timed 25foot walk disease durationresults various regions cervical cord progms mhi higher compared hc 95 31 p 004 rrms 13 26 p 002 progms mhi associated edss r 042052 9hpt r 045052 conclusion myelin abnormalities within clinically eloquent areas related clinical disability mwi metrics potential role monitoring subclinical disease progression adjudicating treatment efficacy new therapies targeting progmspmid33749378 doi101177 13524585211001780,1.0
brief report enhanced dr1mmog3555 treatment severe eae mif1deficient male mice cell immunol 2021 sep 11104439 doi 101016 jcellimm2021104439 online ahead printabstractmacrophage migration inhibitory factor mif1 homologue ddopachrome tautomerase mif2 share common cd74 receptor function innately enhance severity multiple sclerosis ms well experimental autoimmune encephalomyelitis eae model ms previously demonstrated genetically highmifexpressing male subjects relapsing ms significantly greater risk conversion progressive ms pms lowermifexpressing males expand observation utilized mif1 mif2 mif1 2dualdeficient male mice discern greater contribution inflammatory factors eae mice severe vs moderate clinical disease signs shown previously mice deficient either mif1 mif2 25 reduction moderate eae compared wt mice significant differences disease onset trajectory however eae induction mice deficient mif1 mif2 genes result reduction eae severity result suggests two mif homologues likely affecting pathogenic pathways partially compensate additive synergistic manner however mif1ko mif2ko mif1 2dualko mice severe eae exhibit significant reduction cumulative eae scores compared wt mice mif1ko lesser extent mif1 2dualko mice show significant reduction daily eae scores last 3 days observation mif2ko mice showed modest still consistent reduction span furthermore deletion mif1 resulted massive reduction expression eae complete freunds adjuvantassociated inflammatory factors suggesting delayed involvement mif cd74 axis promoting disease expression explore modulation mif1 mif2 effects eae treated wt mice moderate eae using dr1mmog3555 inhibitor cd74 blocks mif1 mif2 action treatment reduced ongoing moderate eae severity excess 25 suggesting efficient blockade mif cd74 axis diseaseenhancing pathways moreover dr1mmog3555 treatment mice severe eae strongly reversed eae cfaassociated expression inflammatory cytokines chemokines including tnf ccr7 ccr6 ccl8 cxcr3 ccl19 mifdeficient mouse genotypes also exceeded innate mif1 mif2 eae enhancing effects especially mif1ko mice results illustrate therapeutic potential targeting diseaseenhancing mif cd74 pathway male mice moderate severe eae implications treatment highmifexpressing rrms human males risk conversion progressive ms well already transitioned pmspmid34607646 doi101016 jcellimm2021104439,0.0
letter editor comparison ofatumumab diseasemodifying therapies relapsing multiple sclerosis network metaanalysis j comp eff res 2021 oct 5 doi 102217 cer20210123 online ahead printno abstractpmid34608807 doi102217 cer20210123,0.0
evaluation concordance glun1glun2 heteromer livecellbased assay glun1 monomer biochip kit assay antinmdar autoantibody detection j immunol methods 2021 sep 21113150 doi 101016 jjim2021113150 online ahead printabstractantinmethyldaspartate receptor nmdar antibodies frequently detected autoantibodyrelated autoimmune encephalitis antinmdar encephalitis mainly affects young women ovarian teratoma including acute subacute onset psychosis seizures consciousness disturbance dyskinetic involuntary movements autonomic dysfunction others diagnosis based detection antinmdar autoantibodies cerebrospinal fluid csf autoantibody recognizes conformational epitope nmda receptor nmda receptors contain heterotetramers glun1 nr1 glun2 3 nr2 3 glun1 essential form functional receptors synaptic membrane brain thus autoantibodies detected using neurons culture cells expressing conformational receptors cell membrane natural form brain antibodies detected using artificial glun1 monosubunit expressing cells antigens widely used antinmdarantibody test present study two detection systems compared livecellbased assay using human embryonic kidney hek 293 cells expressing glun1 glun2b commercially available glun1monotransfected hek cell biochip system result methods equivalent clinical features groups similar suggesting tests equal clinical significancepmid34560071 doi101016 jjim2021113150,0.0
baseline characteristics effects fingolimod cognitive performance patients relapsingremitting multiple sclerosis eur j neurol 2021 aug 24 doi 101111 ene15081 online ahead printabstractbackground studies reporting baseline determinants cognitive performance treatment effect cognition patients ms limited investigated baseline correlates cognition longterm treatment effects fingolimod 05 mg daily cognitive processing speed cps attention patients relapsingremitting ms rrms methods posthoc analysis pooled data phase 3 freedoms freedoms ii trials n1556 assessed correlation baseline patient demographic disease characteristics baseline paced auditory serial addition test 3 pasat3 scores spearmans rank test changes baseline pasat3 mixed model repeated measures model fingolimod placebo 24 months placebofingolimod switched month 24 120 months groups additionally predictive value pasat3 future disease outcomes assessed cox logistic regression models results among variables assessed lower pasat3 score baseline correlated higher disease burden total brain volume t2 lesion volume expanded disability status scale score longer disease duration older age p00001 fingolimod significantly improved pasat3 scores baseline versus placebo 6 13 p00007 12 11 p0044 24 months 11 p00028 sustained effect overall treatment effect p00012 120 months improvements seen regardless baseline cognitive status pasat quartiles baseline pasat3 score predictive clinical mri measures disease activity month 24 p0001 conclusion early fingolimod treatment may offer longterm cognitive benefit patients rrmspmid34431170 doi101111 ene15081,0.0
systematic assessment 10 biomarker candidates focusing synucleinrelated disorders mov disord 2021 aug 7 doi 101002 mds28738 online ahead printabstractbackground objective diagnostic biomarkers needed support clinical diagnosisobjectives analyze markers various neurodegenerative disorders identify diagnostic biomarker candidates mainly synuclein asyn related disorders asrd serum cerebrospinal fluid csf methods upon initial testing commercially available kits published protocols quantification candidate markers assays following selected total phosphorylated asyn ps129asyn neurofilament light chain nfl phosphorylated neurofilament heavy chain pnfh tau protein tau ubiquitin cterminal hydrolase l1 uchl1 glial fibrillary acidic protein gfap calciumbinding protein b s100b soluble triggering receptor expressed myeloid cells 2 strem2 chitinase3like protein 1 ykl40 cohort comprised participants parkinsons disease pd n 151 multiple system atrophy msa n 17 dementia lewy bodies dlb n 45 tau proteinrelated neurodegenerative disorders n 80 comprising patients progressive supranuclear palsy psp n 38 corticobasal syndrome cbs n 16 alzheimers disease ad n 11 frontotemporal degeneration amyotrophic lateral sclerosis ftd als n 15 well healthy controls hc n 20 receiver operating curves roc area curves auc given markerresults csf total asyn decreased nfl pnfh uchl1 gfap s100b strem2 increased patients neurodegenerative disease versus hc p 005 expected markers highest ad ie uchl1 gfap s100b strem2 ykl40 within asrd csf nfl levels higher msa pd dlb p 005 comparing pd hc interesting serum markers s100b auc 086 strem2 auc 087 nfl auc 078 csf s100b serum gfap highest dlbconclusions levels marker candidates tested serum csf significantly differed disease groups hc stratification pd versus tau asynrelated conditions csf nfl levels best discriminated pd msa csf s100b serum gfap best discriminated pd dlb 2021 authors movement disorders published wiley periodicals llc behalf international parkinson movement disorder societypmid34363416 doi101002 mds28738,0.0
systematic review exercise studies persons multiple sclerosis exploring quality interventions according principles exercise training neurol ther 2021 sep 14 doi 101007 s4012002100274z online ahead printabstractintroduction objective systematic review explore application reporting principles exercise training exercise trials ii components exercise prescription iii adherence towards prescribed programmes randomised controlled trials rcts persons multiple sclerosis pwms methods medline cinahl sportdiscus pubmed embase electronic databases searched 1 january 2000 16 october 2020 rcts comprising least 3 weeks aerobic resistance exercise intervention pwms reported least one physiological outcome published peerreviewed journals eligible inclusionresults 52 rcts included review 58 intervention arms examined none applied four principles exercise training specificity addressed 85 progression 33 overload 59 initial values 26 reversibility 0 diminishing returns 2 trials fiftytwo percent trials reported components exercise prescription 3 trials reported level adherence prescribed exerciseconclusion systematic review reveals exercise training principles respected majority included rcts weak quality reported exercise interventions limits interpretation studies results potentially leads underestimation exercise medicine pwms also vague descriptions exercise prescription adherence impede reproducibility results future studies must attend principles exercise training provide transparent information prescribed performed programmes develop specific valid exercise recommendations pwmssystematic review registration crd42020162671 28 04 2020 prosperopmid34520000 doi101007 s4012002100274z,0.0
letter reply j comp eff res 2021 oct 5 doi 102217 cer20210203 online ahead printno abstractpmid34608814 doi102217 cer20210203,0.0
physical activity health wheelchair users systematic review multiple sclerosis cerebral palsy spinal cord injury arch phys med rehabil 2021 oct 12s00039993 21 014842 doi 101016 japmr202110002 online ahead printabstractobjective understand benefits harms physical activity people may require wheelchair focus people multiple sclerosis ms cerebral palsy cp spinal cord injury sci data sources searches conducted medline cinahl psycinfo cochrane central embase january 2008 november 2020 study selection randomized controlled trials rcts nonrandomized trials cohort studies observed physical activity least 10 sessions 10 days participants ms cp scidata extraction conducted dual data abstraction quality assessment strength evidence measures physical functioning reported individually sufficient data exist grouped function data scantdata synthesis studies provided evidence prevention cardiovascular conditions development diabetes obesity among 168 included studies 44 enrolled participants ms 38 cp 18 sci studies ms found walking ability may improved treadmill training multimodal exercises function treadmill balance exercises motion gaming balance likely improved balance exercises may improved aquatic exercises robotassisted gait training ragt motion gaming multimodal exercises activities daily living adl female sexual function spasticity may improved aquatic therapy sleep may improved aerobic exercises aerobic fitness multimodal exercises cp balance may improved hippotherapy motion gaming function cycling treadmill hippotherapy sci adl may improved ragtconclusion depending population type exercise physical activity associated improvements walking function balance depression sleep adl spasticity female sexual function aerobic capacity harms physical activity reported studies future studies needed address evidence gaps confirm findingspmid34653376 doi101016 japmr202110002,0.0
effects normobaric hypoxic endurance training fatigue patients multiple sclerosis randomized prospective pilot study j neurol 2021 may 18 doi 101007 s00415021105965 online ahead printabstractbackground fatigue one frequent symptoms patients multiple sclerosis ms causing major impact qualityoflife nonpharmacological intervention strategies involve physical activity shown reduce fatigue training normobaric hypoxic conditions thought improve response endurance training may therefore additional benefit normoxic training conditions ms patientsobjective compare effects endurance training hypoxic normoxic conditions fatigue mobility spasticity patients ms inpatient rehabilitationmethods thirtynine patients ms assigned within randomized prospective longitudinal pilot study 1 routine clinical rehabilitation program 2 routine clinical rehabilitation program + normoxic endurance training 3 routine clinical rehabilitation program + hypoxic endurance training 14 days fatigue weimus mfis spasticity msss88 walking endurance 6minwt assessed days 0 7 14results fatigue scores improved significantly groups improvements reached faster groups additionally received endurance training normoxic p 0004 hypoxic p 0002 spasticity scores significantly lower endurance training groups end study compared baseline normoxic p 0048 hypoxic p 0012 hypoxic group increased significantly 6minwt p 0001 conclusions findings demonstrate endurance training provides substantial benefit neurological rehabilitation programs endurance training hypoxic conditions positively influence walking endurance within 2week training intervention warrants investigationspmid34003370 doi101007 s00415021105965,0.0
apamin bbb shuttle effects t cell population experimental autoimmune encephalomyelitisinduced model multiple sclerosis neurotox res 2021 sep 6 doi 101007 s12640021004123 online ahead printabstractmultiple sclerosis ms chronic demyelinating disease central nervous system presented autoimmune manifestations study aimed investigating effects apamin administration activated t cell population experimental autoimmune encephalomyelitis eae ms model thirty mice underwent eae induction randomly divided 5 groups three groups received 10 50 100 g kg apamin fourth group received 1 mg kg dexamethasone fifth group received equivalent amount pbs phosphatebuffered saline intraperitoneally peripheral cd4 + cell memory t cell distribution measured flow cytometer every week also cd4 + cd8 + cell infiltration brain assessed immunohistochemistry observed group receiving 50 g kg apamin lower eae score comparison groups receiving 100 g kg apamin p 0014 also peripheral blood memory cells cd44 + cd62l cd4 + markers decreased apaminadministered groups regarding infiltrated cd8 + cells significant decrease p 0002 observed group receiving 50 g kg apamin compared control group results indicate 50g kg doses apamin effective treatment 14 days reduced severity symptoms infiltration cd8 + cells cns moreover increased myelin density decreased circulation cd62l cd44l cd44 + memory t cells appears apamin plays critical role regulating immunity reducing complications autoimmune mspmid34487326 doi101007 s12640021004123,1.0
analysis gadolinium retention experimental autoimmune encephalomyelitis eae murine model multiple sclerosis j trace elem med biol 2021 aug 2 68126831 doi 101016 jjtemb2021126831 online ahead printabstractobjectives aim study quantitatively investigate preclinical level extent gd retention cns peripheral organs immunemediated murine models experimental autoimmune encephalomyelitis eae multiple sclerosis compared control animals upon injection gadodiamide influence gadolinium based contrast agent administration timing course eae development also monitoredmethods eae mice injected three doses 12 mmol kg gadodiamide three different time points eae development sacrificed 21 39 days organs collected amount gd quantified inductively coupled plasmamass spectrometry transmission electron microscopy tem mri techniques applied add spatial qualitative information obtained resultsresults spinal cord eae group 21 days gadodiamide administration significantly higher accumulation gd occurred conversely encephalon lower amount gd retention reached even differences emerged eae controls mice 39 days amounts retained gd markedly decreased tem validated presence gd cns mri encephalon 71t highlight hyper intense regionconclusion spinal cord eae mice mostly damaged region specific animal model preferential transient accumulation gd observed encephalon gd retention mostly related inflammation occurring upon immunization rather demyelinationpmid34364067 doi101016 jjtemb2021126831,1.0
recurrence risk first remote symptomatic seizure adults epilepsy epilepsia open 2021 sep 24 doi 101002 epi412543 online ahead printabstractthe ilae practical definition epilepsy one seizurepossibility diagnose epilepsy first seizure recurrence risk high recurrence risk first seizure brain disorders first remote seizure often high varies etiology specific information needed clinical practice review describes etiologyspecific recurrence risks adults first remote seizure stroke traumatic brain injury infections dementia multiple sclerosis tumors studies short singlecenter retrospective inclusion criteria outcome ascertainment results vary patient categories clearly epilepsy threshold recurrence risk surprisingly little data important etiologies like brain infections besides stroke severe tbi sufficiently high recurrence risk early epilepsy diagnosis studies needed preferably prospective ones literature uninformative regarding seizures qualify remote clinical implication low level available evidence etiologies stroke seizure recurrence remains appropriate indicator epilepsy patients first remote seizure nonetheless worrying indications diagnostic drift puts patients preexisting brain disorder risk misdiagnosis although drawbacks intermediate term like possible epilepsy perhaps useful cases recurrence risk high epilepsy criteria definitely met first remote seizurepmid34561959 doi101002 epi412543,0.0
optimized mp2rage sequence studying brain cervical spinal cord single acquisition 3t magn reson imaging 2021 sep 10s0730725x 21 001417 doi 101016 jmri202108011 online ahead printabstractmagnetization prepared 2 rapid acquisition gradient echo mp2rage t1 mapping technique used broadly brain recently cervical spinal cord csc growing interest combined investigation brain sc numerous pathologies central nervous system multiple sclerosis ms amyotrophic lateral sclerosis als traumatic injuries now brings need optimization regards specific investigation implies large spatial coverage high spatial resolution short acquisition time high cnr low b1+ sensitivity well high reproducibility robust postprocessing tools t1 quantification different regions brain sc work dedicated protocol referred prbsc optimized simultaneous brain csc t1 mp2rage acquisition 3 t computer simulation optimization protocol applied vivo validation experiments compared previously published state art protocols focusing either brain prb csc prsc reproducibility inroi standard deviations assessed healthy volunteers perspective future clinical use mean t1 values obtained prbsc brain white gray deep gray matters mean inroi sd 792 27 ms 1339 139 ms 1136 88 ms respectively csc t1 values white matter corticospinal posterior sensory lateral sensory rubro reticulospinal tracts 902 41 ms 920 35 ms 903 46 ms 891 41 ms respectively 954 32 ms anterior intermediate gray matter prbsc protocol showed excellent agreement previously proposed prb brain prsc csc high interscan reproducibility coefficients variation 052 036 112 062 brain csc respectively optimized protocol covering brain csc submillimetric isotropic spatial resolution one acquisition less 8 min opens great perspectives clinical applications focusing degenerative tissue encountered ms alspmid34517015 doi101016 jmri202108011,0.0
optical coherence tomography multiple sclerosis 3year prospective multicenter study ann clin transl neurol 2021 nov 18 doi 101002 acn351473 online ahead printabstractobjective evaluate changes 3 years thickness inner retinal layers including peripapillary retinal nerve fiber layer prnfl combined macular ganglion cell inner plexiform layers mgcipl individuals relapsingremitting multiple sclerosis rrms versus healthy controls determine whether optical coherence tomography oct sufficiently sensitive reproducible detect small degrees neuroaxonal loss time correlate changes brain volume disability progression measured expanded disability status scale edss methods individuals rrms 28 centers n 333 matched 64 healthy participants oct scans performed heidelberg spectralis machines baseline 1 month 6 months 6monthly thereafter results oct measurements highly reproducible baseline 1 month intraclass correlation coefficient 098 significant inner retinal layer thinning observed individuals multiple sclerosis ms compared controls regardless previous msassociated optic neuritisgroup differences 95 ci 3 years prnfl 186 254 117 m mgcipl 203 278 128 m p 00001 effect sizes 039 034 greater inner retinal layer atrophy observed individuals diagnosed rrms 3 years versus 5 years prnfl p 005 mgcipl p 001 brain volume decreased 13 individuals ms 3 years compared 05 control subjects effect size 076 mgcipl atrophy correlated brain atrophy p 00001 correlation oct data disability progressioninterpretation oct potential estimate rates neurodegeneration retina brain effect size oct smaller magnetic resonance imaging based heidelberg spectralis data acquired study increased early diseasepmid34792863 doi101002 acn351473,0.0
treatment electrical stimulation sensory nerves improves motor function disability status persons multiple sclerosis pilot study j electromyogr kinesiol 2021 oct 13 61102607 doi 101016 jjelekin2021102607 online ahead printabstractdeclines motor function closely associated decreases sensory function multiple sclerosis ms purpose study assess changes motor function disability status elicited transcutaneous electrical nerve stimulation tens limb muscles individuals ms fifteen persons ms 11 agematched healthy controls evaluated receiving 9 treatment sessions tens applied tibialis anterior rectus femoris muscles leg median nerve thenar eminence hand evaluation session involved completing two questionnaires fatigue walking limitations assessing walking performance 2min test 25ft test dynamic balance chairrise test manual dexterity grooved pegboard test muscle function hands legs strength force steadiness tests ms group exhibited improvements 25ft test p 0001 2min test p 0002 chairrise test p 0008 grooved pegboard test p 0008 reductions selfreported levels fatigue walking limitation scores p 002 d 052 p 0008 r 050 respectively contrast statistically significant changes control group significant changes either muscle strength force steadiness either group tens elicited significant improvements motor function selfreported disability status persons ms improvements reached clinically meaningful levelspmid34710779 doi101016 jjelekin2021102607,1.0
switch inflammation spleen cells cd40targeted plga nanoparticles containing dimethyl fumarate colloids surf b biointerfaces 2021 sep 1 208112091 doi 101016 jcolsurfb2021112091 online ahead printabstractthe purpose study designing synthesizing plga formulation targeted anticd40 monoclonal antibody suitable physicochemical properties dimethyl fumarate dmf drug delivery system minimal cytotoxicity therefore research performed determine effect anticd40mabdmfnps expression il1 il6 tnf cytokine genes mouse splenocytes toxicity different groups namely free plga free dmf dmfcontaining plga anticd40mabdmfnps evaluated mtt assay plga formulations conjugated mabcd40 loaded dmf drug showed little cytotoxic effect mouse splenocytes qrtpcr method subsequently used assess effect mentioned groups expression il1 tnf il6 genes treatment cells dmf alone polymer carriers expression il1 il6 tnf cytokine genes significantly reduced decrease expression markedly higher antibodytargeted nanoparticles group relative treatment groups results area promising provide good basis future studies regardpmid34507070 doi101016 jcolsurfb2021112091,0.0
position cladribine tablets management relapsingremitting multiple sclerosis expert narrative review united arab emirates neurol ther 2021 apr 23 doi 101007 s40120021002436 online ahead printabstractthe use immune reconstitution therapies irt patients relapsingremitting multiple sclerosis rrms associated prolonged period freedom relapses absence continuously applied therapy cladribine tablets diseasemodifying treatment dmt indicated highly active relapsing multiple sclerosis ms defined clinical imaging features treatment cladribine tablets effective well tolerated patients active ms disease low burden monitoring following treatment article expert group specialist neurologists involved care patients ms united arab emirates provides consensus recommendations practical use cladribine tablets according presenting phenotype patients rrms irt approach may especially useful patients highly active ms insufficiently responsive treatment firstline dmt likely adhere poorly continuous therapeutic regimen treatmentnave patients high disease activity first presentation patients planning family prepared wait least 6 months end treatment information available date suggest adverse interaction cladribine tablets covid19 infection data unavailable time regarding efficacy covid19 vaccination patients treated cladribine tablets robust immunological responses covid19 infection vaccines observed patients receiving treatment treatment cladribine tablets per se represent barrier vaccinationpmid33891277 doi101007 s40120021002436,0.0
review transporter substrate inhibitor inducer characteristics cladribine clin pharmacokinet 2021 aug 26 doi 101007 s40262021010653 online ahead printabstractcladribine nucleoside analog phosphorylated target cells b tlymphocytes active adenosine triphosphate form 2chlorodeoxyadenosine triphosphate cladribine tablets 10 mg mavenclad administered 10 days per year 2 consecutive years 35mg kg cumulative dose 2 years used treat patients relapsing multiple sclerosis atpbinding cassette solute carrier nucleoside transporter substrate inhibitor inducer characteristics cladribine reviewed article available evidence suggests distribution cladribine across biological membranes facilitated number uptake efflux transporters among key atpbinding cassette efflux transporters breast cancer resistance protein shown efficient transporter cladribine pglycoprotein transport cladribine well intestinal absorption distribution throughout body intracellular uptake cladribine appear exclusively mediated equilibrative concentrative nucleoside transporters specifically ent1 ent2 ent4 cnt2 low affinity cnt3 renal excretion cladribine appears likely driven breast cancer resistance protein ent1 pglycoprotein latter may play role despite poor cladribine transport efficiency view renal abundance pglycoprotein evidence solute carrier uptake transporters organic anion transporting polypeptides organic anion transporters organic cation transporters involved transport cladribine available vitro studies examining inhibitor characteristics cladribine total 13 major atpbinding cassette solute carrier cnt transporters indicate vivo inhibition transporters cladribine unlikelypmid34435310 doi101007 s40262021010653,0.0
precontrast t1weighted imaging spinal cord may unnecessary patients multiple sclerosis eur radiol 2021 jun 9 doi 101007 s00330021080774 online ahead printabstractobjectives multiple sclerosis ms inflammatory disease frequently involving spinal cord can assessed magnetic resonance imaging mri hypothesize precontrast t1w imaging add diagnostic value routine spinal mri followup patients msmethods 3t mri scans including pre postcontrast t1w well t2w images 265 consecutive patients mean age 40 13 years 169 women suspected ms analyzed retrospectively images assessed two separate reading sessions first excluding second including precontrast t1w images two independent neuroradiologists rated number contrastenhancing ce lesions well diagnostic confidence 1 unlikely 5 high overall image quality artifacts results compared using wilcoxon matchedpairs signedrank tests weighted cohens kappa results fiftysix ce lesions found 43 patients significant differences diagnostic confidence readings readers reader 1 p 0058 reader 2 p 0317 interrater concordance moderate regarding artifacts 0418 overall image quality 0504 thirtyone black holes found 25 patients high diagnostic confidence reader 1 404 081 reader 2 380 092 substantial interrater concordance 0700 conclusions availability precontrast t1w images significantly increase diagnostic confidence detection rate ce lesions spinal cord patients ms thus precontrast t1w sequences might omitted routine spinal mri followup exams however special unclear clinical situations certainty contrast enhancement requiredkey points availability precontrast t1w images increase diagnostic confidence detection rate contrastenhancing lesions spinal cord ms patients excluding precontrast t1w sequences reduces scan time thus providing time sequences increasing patients compliancepmid34109486 doi101007 s00330021080774,0.0
longterm ozone exposure mortality neurological diseases canada environ int 2021 aug 9 157106817 doi 101016 jenvint2021106817 online ahead printabstractbackground increasing interest health effects air pollution however relationships ozone exposure mortality attributable neurological diseases remain unclearobjectives assess associations longterm exposure ozone death parkinsons disease dementia stroke multiple sclerosismethods analyses based 2001 canadian census health environment cohort census participants linked vital statistics records 2016 resulting cohort 35 million adults 51 045 700 personyears 8 500 51 300 43 300 1 300 deaths parkinsons dementia stroke multiple sclerosis respectively tenyear average ozone concentrations estimated chemical transport models adjusted ground measurements assigned subjects based postal codes cox proportional hazards models used calculate hazard ratios hrs deaths four neurological diseases adjusting eight common demographic socioeconomic factors seven environmental indexes six contextual covariatesresults fully adjusted hrs parkinsons dementia stroke multiple sclerosis mortalities related one interquartile range increase ozone 101 ppb 109 95 confidence interval 104114 108 106110 106 104109 135 120151 respectively covariates influence significance ozonemortality associations except airshed ie broad region canada period 20012016 566 501 377 1911 deaths parkinsons dementia stroke multiple sclerosis respectively attributable ozone exposureconclusions found positive associations ozone exposure mortality due parkinsons dementia stroke multiple sclerosispmid34385046 doi101016 jenvint2021106817,0.0
delayed amantadine toxicity causing apparent progression multiple sclerosis mult scler 2021 sep 513524585211035737 doi 101177 13524585211035737 online ahead printabstractbackground amantadine sometimes used treat fatigue multiple sclerosisobjectives report patient secondary progressive multiple sclerosis spms developed lateonset side effects amantadine initially felt represent progression spmsmethods single retrospective case reportresults symptoms cognitive deterioration ataxia hallucinations resolved completely cessation amantadine prescribed several years beforehandconclusion clinicians involved management symptoms spms aware potential cumulative side effects drugs used treat symptoms consider potential role precipitating neurological deteriorationpmid34486465 doi101177 13524585211035737,0.0
potential protective role nod2 polymorphism susceptibility multiple sclerosis associated interferon therapy biomed rep 2021 dec 15 6 100 doi 103892 br20211476 epub 2021 sep 30abstractpattern recognition receptors specific nucleotidebinding oligomerization domain protein 2 polymorphisms may involved pathogenesis multiple sclerosis ms may also play role formation neutralizing antibodies interferon inf may exhibit lowered efficacy identification polymorphisms may useful early identification potential nonresponders allow modification treatment regimens earlier differences genotype distribution allele frequency rs3135499 rs2066842 nod2 polymorphisms patients ms healthy controls analysed present study group patients divided responders nonresponders inf therapy evaluate association polymorphisms response therapy differences genotype frequencies responder nonresponder groups observed however statistically significant difference genotype frequencies tt homozygotes rs2066842 patients ms healthy controls observed 2118 p0003 recessive genotype model allele distribution rs2066842 suggest genotype tt allele t protective ms odds ratio 012 represents 833x lower risk ms individual tt genotype significantly lower incidence tt genotype rs2066842 patients ms suggests tt genotype t allele may protective genetic factor mspmid34667597 pmcpmc8517767 doi103892 br20211476,0.0
leveraging diet engineer gut microbiome nat rev gastroenterol hepatol 2021 sep 27 doi 101038 s41575021005127 online ahead printabstractautoimmune diseases including inflammatory bowel disease multiple sclerosis rheumatoid arthritis distinct clinical presentations share underlying patterns gut microbiome perturbation intestinal barrier dysfunction potentially common microbial drivers advocate treatment strategies aimed restoring appropriate microbiome function individual variation host factors makes uniform approach unlikely perspective consolidate knowledge dietmicrobiome interactions local inflammation gut microbiota imbalance host immune dysregulation understanding incorporating effects individual dietary components microbial metabolic output host physiology examine potential dietbased therapies autoimmune disease prevention treatment also discuss tools targeting gut microbiome faecal microbiota transplantation probiotics orthogonal niche engineering optimized using custom dietary interventions approaches highlight paths towards leveraging diet precise engineering gut microbiome time increasing autoimmune diseasepmid34580480 doi101038 s41575021005127,0.0
health services utilization prior amyotrophic lateral sclerosis diagnosis provincewide study individuals treated riluzole ontario canada muscle nerve 2021 aug 26 doi 101002 mus27405 online ahead printabstractintroduction aims amyotrophic lateral sclerosis als symptoms mimic conditions often require multiple physician healthcare contacts investigation accurate diagnosis examined type frequency healthcare service utilization prior als diagnosis tracheostomyfree survival sex rurality among individuals treated riluzole ontario canadamethods populationbased cohort study used administrative databases identify patients aged 18+ years diagnosed als started riluzole april 2002march 2018 using poisson regression rate ratios healthcare utilization atypical diagnostic tests unnecessary therapeutic interventions five years prior als diagnosis compared sex rurality tracheostomyfree survival diagnosis compared groups using kaplanmeier estimators proportional hazards modelsresults 1071 patients als identified mean age 70 years 563 526 men 134 125 rural residents number physician visits increased 18 months prior als diagnosis observed modest sex differences healthcare utilization rural patients lower neurologist visit rates rr 078 95ci 070087 significantly likely receive atypical diagnostic test unnecessary therapeutic intervention rr 180 95ci 104310 tracheostomyfree survival differ sex logrank pvalue 078 rurality pvalue 084 discussion given disparities observed healthcare rural als patients policy strategies needed ensure patients timely access care along pathway symptom onset als diagnosis enable access new therapeutics clinical trials article protected copyright rights reservedpmid34437716 doi101002 mus27405,0.0
advanced glycation endproducts potential triggering factors selfreactivity myelin antigens multiple sclerosis med hypotheses 2021 oct 9 157110702 doi 101016 jmehy2021110702 online ahead printabstractmultiple sclerosis ms demyelinating autoimmune disease autoreactive t lymphocytes infiltrate central nervous system cns react antigens derived proteins myelin sheath reason t lymphocytes recognize certain myelin antigens exogenous activating autoimmune response remains unknown represents key understand pathogenesis ms neurons characterized elevated glycolytic metabolism methylglyoxal mg highly reactive oxoaldehyde spontaneously formed byproduct glycolysis reacts proteins nucleotides phospholipids forming stable adducts called advanced glycation endproducts ages several studies demonstrate mgderived ages accumulate plasma brain ms patients furthermore evidences postmyelinated oligodendrocytes myelinforming glial cells increase glycolytic metabolism maintain survival functions likely explaining progressive accumulation mg ms lesions hypothesis proposed mgderived ages accumulated proteins composing myelin sheath responsible altered antigen presentation process mimicking exogenous antigens triggering autoimmune response hypothesis will experimentally confirmed new pathogenic mechanism ms will identifiedpmid34666261 doi101016 jmehy2021110702,1.0
clinical neuroimaging findings mogad mri oct clin exp immunol 2021 jun 21 doi 101111 cei13641 online ahead printabstractmyelin oligodendrocyte glycoprotein antibody associated disorders mogad rare children adults recently suggested autoimmune neuroinflammatory group disorders different aquaporin4 autoantibody associated neuromyelitis optica spectrum disorder classic multiple sclerosis vivo imaging mogad patient central nervous system shown distinguishing features evaluating magnetic resonance imaging brain spinal cord optic nerves well retinal imaging using optical coherence tomography review discuss key clinical neuroimaging characteristics paediatric adult mogad describe imaging techniques may used study group disorders discuss image analysis methods led recent insights consideration future studiespmid34152000 doi101111 cei13641,1.0
pharmacological perturbation reveals deficits d2 receptor responses thap1 null mice ann clin transl neurol 2021 nov 21 doi 101002 acn351481 online ahead printabstractthe primary dystonia dyt6 caused mutations transcription factor thanatosassociated protein 1 thap1 understand thap1s functions generated mice lacking thap1 nervous system thap1 loss causes locomotor deficits associated transcriptional changes since many genes misregulated involve dopaminergic signaling pharmacologically challenged two striatal canonical dopamine pathways direct regulated d1 receptor indirect regulated d2 receptor discovered depleting thap1 specifically interferes d2 receptor responses pointing selective misregulation indirect pathway dyt6 implications pathogenesis treatmentpmid34802187 doi101002 acn351481,0.0
novel ifitm5 variant associated phenotype osteoporosis calvarial doughnut lesions case report calcif tissue int 2021 jun 22 doi 101007 s00223021008785 online ahead printabstractosteogenesis imperfecta oi decreased bone density disorders comprise heterogeneous group heritable diseases skeletal fragility recently discovered mutations sgms2 encoding sphingomyelin synthetase 2 result aberrant sphingomyelin metabolism lead novel form oi termed osteoporosis calvarial doughnut lesions opcdl moderate severe skeletal fragility variable cranial hyperostotic lesions study describes japanese family skeletal phenotype opcdl affected individuals moderately severe childhoodonset skeletal fragility multiple longbone fractures scoliosis bone deformities addition exhibit multiple cdls calvarial bumps central radiolucency peripheral radiopacity however sgms2 sequencing normal instead wholeexome sequencing identified novel ifitm5 missense mutation c143ag pn48s classified vus acmg ifitm5 encodes osteoblastrestricted protein bril recurrent c14ct mutation 5 utr region results oi type v distinctive subtype oi associated hyperplastic callus formation ossification interosseous membranes patients described phenotype clearly different oi type v hyperostotic cranial lesions feature previously unreported association ifitm5 findings expand genetic spectrum opcdl indicate diverse phenotypic consequences pathogenic ifitm5 variants imply important role bril cranial skeletogenesispmid34156493 doi101007 s00223021008785,1.0
validating diagnosis multiple sclerosis using swedish administrative data varmland county acta neurol scand 2021 aug 6 doi 101111 ane13514 online ahead printabstractobjectives multiple sclerosis ms chronic neurodegenerative disease central nervous system identifying ms population level important disease surveillance allocation resources swedish national patient registry npr used study epidemiology ms accuracy resource known aimed validate definition ms using swedish npr vrmland county using longitudinal cohort designmaterials methods data extracted npr total population register swedish ms register medical records years 20012013 fifteen algorithms hospitalizations clinic visits ms developed compared findings medical records acted gold standard definition sensitivity specificity positive negative predictive values ppv npv estimatedresults 805 eligible persons identified npr 763 ms 948 according medical records 544 713 also registered smsreg case definition wellbalanced sensitivity specificity required three clinic hospital visits ms sensitivity 853 95 ci 826878 specificity 810 95ci 659914 conclusions multiple case definitions high sensitivity moderate specificity found suggesting npr can used accurately identify persons mspmid34357597 doi101111 ane13514,0.0
reduction cd11c+ microglia correlates clinical progression chronic experimental autoimmune demyelination neurobiol dis 2021 nov 6105556 doi 101016 jnbd2021105556 online ahead printabstractmultiple sclerosis ms chronic autoimmune demyelinating disease high variability clinical symptoms cases ms appears relapsingremitting disease course later stage transitions irreversible progressive decline neurologic function mechanisms underlying ms progression remain poorly understood experimental autoimmune encephalomyelitis eae animal model ms demonstrate mice develop mild eae immunization myelin oligodendrocyte glycoprotein 3555 prone undergo clinical progression around 30 days eae induction eae progression associated reduction cd11c+ microglia dispersed coalescent parenchymal infiltration found sexdependent differences mediated p38 signaling key regulator inflammation selective reduction cd11c+ microglia female mice cd11cpromoter driven p38 knockout ko correlated increased rate eae progression protected animals found cd11c+ microglia forming contacts astrocyte processes glia limitans immune cells retained within perivascular spaces together study identified pathological hallmarks chronic eae progression suggests cd11c+ microglia may regulate immune cell parenchymal infiltration autoimmune demyelinationpmid34752925 doi101016 jnbd2021105556,1.0
safety pharmacokinetics preliminary efficacy parp inhibitor talazoparib japanese patients advanced solid tumors phase 1 study invest new drugs 2021 jun 23 doi 101007 s10637021011207 online ahead printabstractbackground talazoparib poly adpribose polymerase enzyme inhibitor openlabel nonrandomized phase 1 study talazoparib investigated safety pharmacokinetics preliminary antitumor activity japanese patients locally advanced metastatic solid tumors regardless mutations dna damage repairrelated genes resistant ineligible standard therapiesmethods patients received talazoparib dosed orally 075 1 mg daily using modified 3 + 3 doseescalation scheme primary endpoint doselimiting toxicities first cycle talazoparibresults nine patients median age 620 years included 3 6 patients 075 10 mg oncedaily dose levels respectively doselimiting toxicities reported commonly reported treatmentemergent adverse events 2 patients anemia stomatitis maculopapular rash platelet count decreased neutrophil count decreased alanine aminotransferase increased three patients grade 3 treatmentemergent adverse events anemia brain metastases 1 patient neutrophil white blood cell count decreased patient two patients temporarily discontinued treatment due treatmentemergent adverse event 1 patient required dose reduction neutrophil count decreased 1 mg daily talazoparib exposure cmax auc single multiple dosing slightly higher proportionally talazoparib 1 mg talazoparib 075 mg overall disease control rate 444 including 2 patients stable disease recommended phase 2 dose talazoparib established 1 mg dailyconclusions singleagent talazoparib well tolerated preliminary antitumor activity japanese patients advanced solid tumors clinicaltrialsgov identifier nct03343054 november 17 2017 pmid34160752 doi101007 s10637021011207,0.0
involvement various chemokine#x2f chemokine receptor axes trafficking oriented locomotion mesenchymal stem cells multiple sclerosis patients cytokine 2021 sep 25 148155706 doi 101016 jcyto2021155706 online ahead printabstractmultiple sclerosis ms specific type chronic immunemediated disease immune responses almost run central nervous system cns despite intensive research known treatment ms disease yet introduced thus development novel safe medications needs considered disease management application mesenchymal stem cells mscs emerging approach recruited forthe treatment ms mscs several sources can derived umbilical cord adipose tissue bone marrow chemokines low molecular weight proteins functional activities achieved binding cell surface g proteincoupled receptors gpcrs chemokine chemokine receptors important effective molecules msc trafficking within different tissues hemostatic nonhemostatic circumstances chemokine chemokine receptor axes play pivotal role recruitment oriented trafficking immune cells towards within cns appears chemokine chemokine receptor signaling may important leading mechanisms pathogenesis ms article hypothesized chemokine chemokine receptor axes network crucial efficacious impacts behavior mscs nonetheless exact responsibility axes targeted tropism mscs cns ms patients yet remained fully elucidated therefore reviewed ability mscs migrate home cns ms patients via expression various chemokine receptors response chemokines expressed cells cns tissue provide great source knowledgepmid34583254 doi101016 jcyto2021155706,1.0
galangin ameliorates experimental autoimmune encephalomyelitis mice via modulation cellular immunity j immunotoxicol 2021 dec 18 1 5060 doi 101080 1547691x20211890863abstractmultiple sclerosis ms causes neurologic disabilities effect musculature sensory systems vision largely due demyelination nerve fibers caused chronic inflammation corticosteroid treatments ameliorate symptoms ms successfully cure disease current study application galangin phytochemical flavonoid extracted ginger family alpinis officinarum experimental autoimmune encephalomyelitis eae mouse model ms explored study investigated prophylactic therapeutic activity drug mechanisms acts results revealed galangin 40 80 mg kg lower incidence rate ms alleviate clinical pathological manifestations mice administered galangin presented less limb paralysis lower levels inflammatory cell infiltrates decreased demyelination compared vehicle controls levels cd4+ifn+ th1 cd4+il17a+ th17 cells spinal cords eae mice administered galangin reduced cell types capable expansion surprisingly galangin inhibited antigen presentation cytokine production dendritic cells dc formation cytokines like il6 il12 il23 significantly decreased due galangin coculture models dc tcells taken together data lead one conclude galangin potentially used potent immunoregulatory agent alleviate clinical symptoms reduce prevalence mspmid33770444 doi101080 1547691x20211890863,1.0
nabiximols botulinum toxin injections patients multiple sclerosis efficacy spasticity spasms singlecentre experience neurol sci 2021 mar 19 doi 101007 s10072021051826 online ahead printabstractbackground spasticity common disabling symptom patients multiple sclerosis pwms highlighted many epidemiological studies often severe well treated despite availability evidencebased spasticity management guidelines still great variability everyday therapeutic approach especially complex casesmethods singlecentre study retrospectively evaluated pwmstreated nabiximols botulinum toxin injections bti july 2015 april 2019 clinical demographic data collected severity spasticity spasms recorded modified ashworth scale mas penn spasm frequency scale psfs baseline 1 month treatmentresults evaluated 64 treatments msrelated spasticity 28 patients treated bti 36 patients nabiximols found bti nabiximols effective reducing mas nabiximols bti p 0001 psfs frequency nabiximols p 0001 bti p 0008 intensity nabiximols p 0001 bti p 0016 differences found directly comparing efficacy two treatments except statistical trend favouring bti spasms intensity p 0091 eleven patients treated bti nabiximols four patients continued treatments dropouts due inefficacy least one two therapiesconclusions singlecentre experience highlights bti nabiximols effective treating multiple sclerosisrelated spasticity however bti treatment may effective spasms intensity combined nabiximols bti treatment represent therapeutic option severe spasticitypmid33742336 doi101007 s10072021051826,1.0
selected transient receptor potential channel genes#39 expression peripheral blood mononuclear cells multiple sclerosis hum exp toxicol 2021 sep 269603271211043476 doi 101177 09603271211043476 online ahead printabstracttransient receptor potential channels responsibilities many cellular processes cytokine production cell differentiation cytotoxicity affecting intracellular cation levels intracellular signal pathways multiple sclerosis chronic autoimmune central nervous system cns disease caused environmental genetic factors study aim investigate trpv1trpv4 trpm2 trpm4 trpm7 trpc6 trpa1 mrna expression levels associated inflammatory process peripheral blood mononuclear cells pbmcs relapsingremitting multiple sclerosis rrms patients thirtyfive healthy controls agegender matched thirty patients rrms involved study trpc6 trpa1 trpm2 trpm4 trpm7 trpv1 trpv2 trpv3 trpv4 pbmcs mrna expression levels determined qpcr present study trpc6 trpm7 trpv1 trpv3 trpv4 mrna expressions rrms patients pbmcs decreased significant level compared healthy control group p 000 p 000 p 044 p 000 p 004 respectively decreased expression trpc6 trpm7 trpv1 trpv3 trpv4 pbmcs may associated pathogenesis ms studies required understand mechanism relation trp channels ms autoimmune diseasespmid34569347 doi101177 09603271211043476,0.0
multiple sclerosis structural functional integrity visual system following alemtuzumab therapy j neurol neurosurg psychiatry 2021 jun 29jnnp2021326164 doi 101136 jnnp2021326164 online ahead printabstractobjective investigate potential neuroprotective proremyelinating effects alemtuzumab multiple sclerosis ms using visual pathway modelmethods monitored clinical multifocal visual evoked potential mfvep mri outcomes 30 patients commencing alemtuzumab relapsing ms reference group 20 healthy controls hcs 24 months change mfvep latency primary endpoint change optic radiation lesion diffusion metrics mars letter contrast sensitivity course study secondary endpointsresults patients observed mean shortening mfvep latency 121 ms course study 95 ci 021 221 p0013 altered correction age gender disease duration change t2 lesion volume mean mfvep latency hc group increased course study 072 ms significant analysis chronic t2 lesions patients showed increase normalised fractional anisotropy axial diffusivity baseline 24 months p001 mean mars letter contrast sensitivity improved 24 months vs baseline p0001 driven early improvement patients hcconclusion found evidence partial lesion remyelination alemtuzumab therapy indicating either natural restoration context permissive local milieu potentially independent proreparative mechanism action visual system presents unique opportunity study functionstructure specific effects therapy inform design future phase 2 ms remyelination trialspmid34187865 doi101136 jnnp2021326164,1.0
target engagement firstinclass cxcr7 antagonist act10041239 following multipledose administration mice humans biomed pharmacother 2021 dec 144112363 doi 101016 jbiopha2021112363 epub 2021 oct 28abstractantagonism chemokine receptor cxcr7 shown promising effects diverse disease areas modulation ligands cxcl11 cxcl12 preclinical data firstinclass cxcr7 antagonist act10041239 showed efficacy animal models multiple sclerosis acute lung injury healthy humans singledose administration act10041239 revealed favorable clinical profile report target engagement act10041239 healthy mice humans multiple doses using cxcl11 cxcl12 biomarkers addition safety tolerability concentrationqtc relationship pharmacokinetics pk assessed randomized doubleblind placebocontrolled phase 1 clinical study multipledose act10041239 dosedependently increased cxcl12 plasma concentration across investigated dose range mice humans mice 1100 mg kg bid humans 30200 mg od compared vehicle placebo demonstrating target engagement mouse human pk pd models predicted cxcl12 concentration approached plateau within dose ranges humans act10041239 rapidly absorbed tmax 175301 h terminal t1 2 approximately 19 h steadystate conditions reached day 3 accumulation index 12 female subjects overall higher exposure compared males multipledose act10041239 well tolerated 200 mg daily humans evidence act10041239mediated qtc interval prolongation overall multiple oral doses act10041239 showed target engagement cxcr7 healthy mice humans therefore assessment cxcl12 translational tool investigations patients warranted favorable safety tolerability pk profiles allow clinical developmentpmid34794236 doi101016 jbiopha2021112363,1.0
association rage rs1800624 rs1800625 gene polymorphisms predisposition optic neuritis optic neuritis together multiple sclerosis ophthalmic genet 2021 aug 216 doi 101080 1381681020211952619 online ahead printabstractoptic neuritis demyelinating acute inflammatory disease affects optic nerve classified typical demyelinating atypical idiopathic patients often complain periocular pain visual loss main factor causing optic neuritis still unknown believed might combination genetic environmental factors optic neuritis inflammation disease rage gene selected part inflammation processaim determine relation rage rs1800624 rs1800625 genotypes patients manifestation optic neuritis optic neuritis multiple sclerosis together lithuanian population visual acuity recoveryobjectives patients optic neuritis healthy controls individuals examined genotyping carried using instrument realtime polymerase chain reaction called steponeplus appliedbiosystems statistical analysis performed using ibm spss statistics 200 software free plink software version 107 results results indicate rs1800624 polymorphism statistically significant optic neuritis manifestation p 392 rs1800625 gg genotype associated 75fold increased odds development codominant model 75 95 ci179631313 p 006 69fold increased odds recessive model 6862 95 ci166528288 p 008 allele g associated 19fold increased odds development additive model 1879 95 ci11493072 p 012 haplotype containing ag alleles rs1800624 rs1800625 statistically significantly associated increased risk development 2 1323 p 001 polymorphisms statistically significant importance relation visual acuity recoveryconclusions rage rs1800625 aa genotype decreases risk optic neuritis single nucleotide polymorphisms rage rs1800624 rs1800625 statistically significant importance relation visual acuity recoverypmid34338585 doi101080 1381681020211952619,1.0
vo2peak response heterogeneity persons multiple sclerosis hiit hiit int j sports med 2021 jul 1 doi 101055 a14818639 online ahead printabstractexercise described provoke enhancements cardiorespiratory fitness persons multiple sclerosis pwms however high interindividual variability training responses observed analysis investigates response heterogeneity cardiorespiratory fitness following high intensity interval hiit moderate continuous training mct analyzes potential predictors cardiorespiratory training effects pwms 131 pwms performed hiit mct 35x week cycle ergometer three weeks individual responses classified finally multiple linear regression conducted examine potential associations changes absolute peak oxygen consumption absolute vo2peak kg training modality participants characteristics results show time interaction effect vo2peak kg absolute changes cardiorespiratory responses larger nonresponse proportions smaller hiit vs mct model accounting 86 variance vo2peak kg suggests hiit younger age lower baseline fitness predict higher absolute vo2peak kg following exercise intervention thus work implements novel approach investigates potential determinants cardiorespiratory response heterogeneity within clinical setting analyzes remarkable bigger sample predictors need identified increase knowledge response heterogeneity thereby supporting development individualized training recommendations pwmspmid34198345 doi101055 a14818639,0.0
regulation mtorc1 amino acids mammalian cells general picture recent advances anim nutr 2021 dec 7 4 10091023 doi 101016 janinu202105003 epub 2021 sep 14abstractthe mechanistic target rapamycin complex 1 mtorc1 integrates various types signal inputs energy growth factors amino acids regulate cell growth proliferation mainly 2 direct downstream targets eukaryotic translation initiation factor 4ebinding protein 1 4ebp1 ribosomal protein s6 kinase 1 s6k1 signal arms upstream mtorc1 including energy status stress signals growth factors converge tuberous sclerosis complex tsc ras homologue enriched brain rheb axis amino acids however distinct signals modulate mtorc1 using unique pathway recent years transmission mechanism amino acid signals upstream mtorc1 gradually elucidated sensors signal transmission pathways individual amino acids also discovered help findings propose general picture recent advances demonstrates various amino acids lysosomes cytoplasm golgi sensed respective sensors signals converge mtorc1 form huge complicated signal network multiple synergies antagonisms feedback mechanismspmid34738031 pmcpmc8536509 doi101016 janinu202105003,0.0
lowlevel mosaicism tuberous sclerosis complex four unrelated patients comparison clinical characteristics diagnostic pathways j med genet 2021 jul 30 doi 101002 ajmga62433 online ahead printabstracttuberous sclerosis complex tsc autosomal dominant neurocutaneous syndrome caused either tsc1 tsc2 gene mutations 15 tsc patients remain without genetic diagnosis conventional analysis despite clinical evidence important identify somatic mosaics therapeutic options now available patients tsc1 tsc2 mutations describe clinical genetic characteristics four male tsc patients lowlevel mosaicism patients presented ages 9 months 32 years clinical manifestations varied considerably included brain lesions four patients cardiac rhabdomyomas two young patients skin involvement two patients retinal hamartomas renal angiomyolipomas three patients one patient presented epileptic seizures psychomotor delay low levels mosaicism tsc1 tsc2 mutation found different tissue samples employing next generation sequencing multiple ligationdependent probe amplification five diseaseassociated variants including one secondhit mutation include three truncating mutations one deletion tsc2 one truncating mutation tsc1 sanger sequencing allelespecific oligonucleotide pcr asopcr droplet digital pcr used confirm quantify disclosed mutations genetic identification lowlevel mosaicism tsc remains challenging important optimal surveillance managementpmid34328706 doi101002 ajmga62433,0.0
modelbased economic evaluation cladribine versus alemtuzumab ocrelizumab natalizumab treatment relapsingremitting multiple sclerosis high disease activity chile pharmacoecon open 2021 jul 5 doi 101007 s41669021002827 online ahead printabstractpurpose aim study evaluate cost effectiveness cladribine compared alemtuzumab natalizumab ocrelizumab treatment highly active multiple sclerosis hadms perspective chilean health care public sectormaterials methods markov model used compare costs qualityadjusted lifeyears qalys 45year time horizon using 3 discount rate costs outcomes natural history disease modeled terms progression disability according expanded disability status scale edss network metaanalysis used source comparative effectiveness disability progression annual relapse rates differences costs outcomes modeled 10 years due high temporal uncertainty ocrelizumab assumed efficacy cladribine due lack data direct costs taken national tariffs expressed 2019 us dollars utilities edss health states obtained literature secondorder uncertainty characterized deterministic probabilistic sensitivity analysisfindings compared natalizumab current strategy covered chile cladribine associated incremental costs qalys us70 989 1875 respectively incremental costeffectiveness ratio icer 37 861 ocrelizumab extendedly dominated cladribine natalizumab alemtuzumab dominated cladribine scenario analysis 10 discount modify results substantially showed decrease icer cladribine versus natalizumab icer 29 833 qaly implications cladribine new oral alternative treat patients hadms expected produce higher qalys evaluated alternatives context conservative analysis cladribine considered cost effective chilean health care public sector using 1 gdp per capita threshold however reasonable discount scenarios cladribine becomes attractive alternative health systempmid34224114 doi101007 s41669021002827,0.0
economic evaluations relapsing multiple sclerosis evolved time systematic literature review neurol ther 2021 jul 19 doi 101007 s40120021002641 online ahead printabstractintroduction introduction diseasemodifying therapies dmts relapsing multiple sclerosis rms last two decades prompted economic assessments treatments reimbursement authorities aim systematic literature review evaluate modeling approach data sources used economic evaluations dmts rms identify differences similarities explore economic evaluation models evolved timemethods medline embase ebm reviews databases searched using ovid platform database inception 25 december 2019 subsequently updated 17 february 2021 addition health technology assessment agency websites key conference proceedings gray literature relevant websites screened quality included studies assessed using drummond philips checklistsresults total 155 publications 30 health technology assessment hta reports included costutility analysis 73 studies 25 hta reports funded medicines manufacturers n 65 top three countries studies conducted usa n 29 uk n 16 spain n 10 studies predominantly used markov cohort models 94 studies 25 htas structured based expanded disability status scale edss 21 health states 20 studies 12 hta reports london ontario british columbia data sets commonly used sources natural history data n 33 n 13 twelve studies ten htas uk assumed waning dmt effect long term uncommon studies countries nineteen studies adjusted multiple sclerosis ms specific mortality estimates 18 studies used data national life table without adjustment studies prominently referred mortality data two decades old data treatment effect generally obtained randomized controlled trials 43 studies 7 htas published evidence synthesis 23 studies 24 htas utility estimates derived either published studies supplemented data rcts models used lifetime horizon n 37 1year cycle length n 63 conclusion expected similarities well differences observed across different economic models available evidence suggests models continue using markov cohort model 21 edssbased states however allowing transition lower edss state assuming sustained treatment effect reference data sources models consider using contemporary msspecific mortality data recent natural history data countryspecific utility data available case data unavailability sensitivity analysis using multiple sources data conducted addition future models incorporate clinically relevant outcomes cognition vision psychological aspects rms able present comprehensive value dmtspmid34279847 doi101007 s40120021002641,0.0
clinical radiological features cerebral amyloid angiopathyrelated inflammation neurol sci 2021 aug 10 doi 101007 s1007202105490x online ahead printabstractobjectives want report clinical radiological features cohort patients diagnosed cerebral amyloid angiopathyrelated inflammation caari according boston criteria additionally disclose atypical clinical characteristics observed provide knowledge novel entitymethods describe 5 patients probable caari according validation study proposed criteria diagnosis caari university hospital josep trueta girona consider clinical characteristics include response immunotherapy csf findings mri features patients neurologic outcomes assessed using modified rankin scale mrs results collected 5 patients admitted probable caari women median age 72 years median mrs score onset disease 1 parietal lobes affected clinically well radiologically two patients intracranial hemorrhage decreased levels csf amyloid beta 42 40 protein observed corticosteroids used four patients remarkable improvement observed themconclusions caari condition predominantly affects parietal lobes according case series involvement seems directly related greater burden microbleeds cortical siderosis wmh lobar hemorrhages lobes decreased levels csf amyloid beta protein plus increased total tau protein considered part diagnostic criteria caari recommend corticosteroids using demonstrated effective managing caaripmid34374865 doi101007 s1007202105490x,0.0
corona pandemic multiple sclerosis vaccinations implications patientspart 2 vaccine technologies nervenarzt 2021 jul 7 doi 101007 s00115021011545 online ahead printabstractalong challenges posed globally circulating covid19 pandemic epochal advances field vaccine technologies addition traditionally used dead live proteinbased vaccines vectorbased genebased vaccines gained enormous attention course health crisis aim article provide overview multiple sclerosis ms vaccination recent advances sarscov2 vaccine landscape well detailed discussion various vaccine technologies finally clear recommendations context diseasemodifying treatment vaccination ms highlightedpmid34232358 doi101007 s00115021011545,1.0
serum neurofilament light chain glial fibrillary acidic protein aqp4iggseropositive neuromyelitis optica spectrum disorders multiple sclerosis cohort study j neurochem 2021 jul 19 doi 101111 jnc15478 online ahead printabstractwe investigated serum neurofilament light chain snfl glial fibrillary acidic protein sgfap levels cohort chinese patients neuromyelitis optica spectrum disorders nmosd multiple sclerosis ms relation clinical disease course treatment snfl sgfap levels determined ultrasensitive single molecule array simoa assay patients nmosd n102 ms n98 healthy controls hcs n84 notably 13 patients nmosd 27 patients ms enrolled 1year followup cohort levels compared data clinical course disease duration expanded disability status scale edss score lesions mri higher levels snfl sgfap found subjects nmosd ms hcs snfl median 1211 175 vs 888 pg ml p005 sgfap median 1302 1604 vs 8001 pg ml p005 moreover snfl levels higher relapse phase ms relapse phase nmosd 3002 vs 1457 pg ml p005 sgfap levels higher remission phase ms remission phase nmosd 1598 vs 1245 pg ml p001 higher sgfap snfl quotient relapse differentiated nmosd ms multivariate analyses indicated sgfap levels associated edss score nmosd p005 1year followup snfl sgfap levels decreased nmosd patients remission snfl levels decreased ms patients remission sgfap snfl potential blood biomarkers diagnosing monitoring nmosd mspmid34278578 doi101111 jnc15478,0.0
brain mri activity year pregnancy can predict postpartum clinical relapses mult scler 2021 mar 3013524585211002719 doi 101177 13524585211002719 online ahead printabstractbackground fewer multiple sclerosis ms relapses pregnancy although relapse risk increases early postpartum period predicted prepregnancy pregnancy disease activity studiesobjective aim study evaluate correlation magnetic resonance imaging mri changes year pregnancy relapse rate year postpartummethods observational retrospective casecontrol study included 172 pregnancies 118 females ms statistical analyses used evaluate correlation mri postpartum relapses clustered logistic regression used investigate predictors early postpartum relapsesresults found significant correlation activemri prepregnancy relapses first 3 months postpartum p 0001 expanded disability status scale edss prepregnancy relapses first 3 months postpartum also significantly correlated p 0009 using multivariate model predicted women will experience postpartum relapse edss activemri prepregnancy 967 specificity p 0001 conclusion activemri prepregnancy strong sensitive predictor early postpartum relapse regardless whether woman clinical evidence disease activity prior conception delivery finding provide clinicians strategy minimize postpartum relapse risk women ms planning pregnancypmid33783260 doi101177 13524585211002719,0.0
demyelinating disease multiple sclerosis patient psoriatic arthritis treated adalimumab casebased review rheumatol int 2021 sep 23 doi 101007 s00296021049950 online ahead printabstractover past two decades tumor necrosis factor tnf inhibitors became one important drugs treatment patients psoriatic arthritis unfortunately patients exhibit unwanted side effects treatment describe patient psoriasis psoriatic arthritis uveitis treated adalimumab 4 months treatment developed clinical neuroradiological signs demyelinating disease central nervous system experienced signs symptoms neurological disease prior adalimumab administration detailed neurological workup diagnosed relapsingremitting type multiple sclerosis treated oral pulse glucocorticoids later dimethyl fumarate adalimumab discontinued question remains demyelination induced tnf blockade unmasked introduction cytokine blocking agent patients suffering inflammatory arthritis treating disease target well close followup knowledge potential side effects treatment remains crucial good clinical practicepmid34557936 doi101007 s00296021049950,1.0
correction clinical demographic characteristics primary progressive multiple sclerosis argentina argentinean registry cohort study relevarem neurol sci 2021 sep 24 doi 101007 s10072021056054 online ahead printno abstractpmid34557969 doi101007 s10072021056054,0.0
cerebrospinal fluid levels lglutamate signal central inflammatory neurodegeneration multiple sclerosis j neurochem 2021 sep 21 doi 101111 jnc15518 online ahead printabstractexcessive extracellular concentrations lglutamate lglu can neurotoxic contribute neurodegenerative processes multiple sclerosis ms association cerebrospinal fluid csf lglu levels clinical features inflammatory biomarkers patients ms remains unclear 179 ms patients relapsing remitting rr n 157 secondary progressive primary progressive sp pp n 22 csf levels lglu diagnosis determined compared obtained group 40 patients noninflammatory nondegenerative disorders disability time diagnosis 1 year follow assessed using expanded disability status scale edss csf concentrations lactate large set proinflammatory antiinflammatory molecules explored csf levels lglu slightly reduced ms patients compared controls rrms patients lglu levels correlated edss 1 year follow moreover ms patients significant correlations found lglu csf levels lactate inflammatory molecules interleukin il 2 il6 il1 receptor antagonist altered expression lglu associated disability progression oxidative stress inflammation findings identify csf lglu candidate neurochemical marker inflammatory neurodegeneration mspmid34547109 doi101111 jnc15518,0.0
childhood obesity multiple sclerosis mendelian randomization study mult scler 2021 mar 2213524585211001781 doi 101177 13524585211001781 online ahead printabstractbackground higher childhood body mass index bmi associated increased risk multiple sclerosis ms objective evaluate whether childhood bmi causal influence ms whether putative effect independent early adult obesity pubertal timingmethods performed mendelian randomization mr using summary genetic data 14 802 ms cases 26 703 controls largescale genomewide association studies provided estimates bmi childhood n 47 541 adulthood n 322 154 multivariable mr examined direct effects timepoint adjusted age puberty findings replicated using uk biobank n 453 169 results higher genetically predicted childhood bmi associated increased odds ms odds ratio 126 sd bmi increase 95 confidence interval ci 107150 however little evidence direct effect adjusting adult bmi 103 95 ci 070153 conversely effect adult bmi persisted independent childhood bmi 143 95 ci 101203 addition age puberty alter findings uk biobank analyses showed consistent results sensitivity analyses provided evidence pleiotropyconclusion genetic evidence supports association childhood obesity ms susceptibility mediated persistence obesity early adulthood independent pubertal timingpmid33749377 doi101177 13524585211001781,0.0
perioperative botulinum toxin injections enhance surgical outcomes patients spasticity preoperative intraoperative postoperative case reports arch rehabil res clin transl 2021 jan 12 3 1 100101 doi 101016 jarrct2021100101 ecollection 2021 marabstractspasticity causes array disabilities turn may lead need surgical intervention spasticity may also negatively affect surgical outcomes report reviews potential benefit perioperative surgery botulinum toxin bont injections 3 patients spasticity due spinal cord injury stroke multiple sclerosis discuss perioperative bont 3 time periods preoperatively intraoperatively postoperatively cases demonstrate use perioperative bont decreasing pain improving wound healing improving surgical outcomes conclude discussing potential use perioperative bont surgical interventions patients spasticity need highquality research fieldpmid33778474 pmcpmc7984973 doi101016 jarrct2021100101,0.0
role pd1 pdl1 signaling multiple sclerosis experimental autoimmune encephalomyelitis recent insights future directions mol neurobiol 2021 sep 3 doi 101007 s12035021024957 online ahead printabstractmultiple sclerosis ms autoimmunityrelated chronic demyelination disease central nervous system cns causing young disability currently highly specific immunotherapies ms still lacking programmed cell death 1 pd1 immunosuppressive costimulatory molecule expressed activated t lymphocytes b lymphocytes natural killer cells immune cells pdl1 ligand pd1 expressed t lymphocytes b lymphocytes dendritic cells macrophages pd1 pdl1 delivers negative regulatory signals immune cells maintaining immune tolerance inhibiting autoimmunity review comprehensively summarizes current insights role pd1 pdl1 signaling ms animal model experimental autoimmune encephalomyelitis eae potentiality pd1 pdl1 biomarkers therapeutic targets ms will also discussedpmid34480337 doi101007 s12035021024957,1.0
methyl acetate arrests th1 peripheral immune system alleviates cns inflammation eae int immunopharmacol 2021 nov 16108291 doi 101016 jintimp2021108291 online ahead printabstractmultiple sclerosis ms inflammatory autoimmune disease central nervous system cns mediated immune cells pathogenesis autoimmune diseases degree similarity ms therefore study ms clinical scientific significance autoimmune diseases well widely used organic solvent methyl acetate ma similar structure acetate shown therapeutic mouse model multiple sclerosis found ma effective reducing disease severity experimental autoimmune encephalomyelitis eae pathological sections showed ma reduced inflammatory cell infiltration cns attenuated demyelination spinal cord ma increases proportion th1 cells periphery eae mice mechanistic studies demonstrated ma treatment induces th1 retention peripheral immune system increasing expression levels peripheral th1related chemokines cxcr3 cxcl9 cxcl10 addition observed ma alleviated intestinal inflammation eae mice data showed phenomenon achieved enhancing il10 inhibiting il6 secretion data indicates ma might therapeutic implications autoimmune diseases mspmid34799286 doi101016 jintimp2021108291,1.0
cancer risk multiple sclerosis patients treated azathioprine diseasemodifying therapies italian observational study neurol sci 2021 mar 31 doi 101007 s1007202105216z online ahead printabstractbackground risk malignancy associated sequential diseasemodifying therapies dmts patients multiple sclerosis ms uncertain aim study analyze risk cancer patients ms treated azathioprine aza influence sequential dmts riskmethod retrospectively enrolled cohort azatreated ms patients followed two italian centers 1987 2019 ratio observed expected cancers italian general population calculated standardized incidence ratio sir associations aza dmts cancer estimated cox proportional hazards modelresults identified 500 azatreated ms patients followed median time 97 01457 years 618 treated dmts found 22 cases cancer 44 sir 114 95 ci 098129 significantly increased comparison general population however risk significantly higher quintiles age 3245 sir 121 95 ci 121142 4651 sir 111 95 ci 111132 older cases age aza treatment onset covariate significantly related cancer incidence hr 1049 95 ci 10071093 exposure dmts modify riskconclusion risk malignancy ms patients aza similar general population change dmts sequential treatments increased risk younger ages considered treatment assessmentpmid33791892 doi101007 s1007202105216z,0.0
neuropsychological mri diagnostics secondary progressive multiple sclerosis nervenarzt 2021 apr 23 doi 101007 s00115021011189 online ahead printabstractbackground multiple sclerosis disease continuum initial relapsing remitting course rrms secondary progression spms later stages hitherto approved treatments adequately control phase secondary progression thus early detection spms conversion key issue initiate spmstailored treatment context assessment cognitive functions magnetic resonance imaging mri play important role longitudinal followup ms patientsobjective elucidate importance cognitive testing mri prediction detection spms conversion well discuss strategies disease monitoring optimizing treatment standard clinical care particularly outpatient settingsmaterial methods review article based nonsystematic literature reviewresults standardized cognitive testing can support early diagnosis spms facilitate disease monitoring annual application sensitive screening tests symbol digit modalities test sdmt brief visual memory testrevised bvmtr entire brief international cognitive assessment ms bicams test battery recommended context mri evidence persistent inflammatory activity within 3 years diagnosis well evidence cortical lesions predictive spms conversion standardized mri monitoring markers progression can substantiate clinical neurocognitive signs spms conversionconclusion multidisciplinary patient care involving careful clinical examination neuropsychological testing mri monitoring great significance prediction spms conversion diagnostics enables early treatment adaptation since pharmacological interventions spms differ rrms continuous clinical neuropsychological mri vigilance enable stringent monitoring treatment outcomes respect neuroinflammatory neurodegenerative activity well treatmentrelated complicationspmid33891150 doi101007 s00115021011189,0.0
sarscov2 infection alemtuzumab multiple sclerosis patient milder disease symptoms comparison coinfected relatives case report review literature neurol sci 2021 aug 24 doi 101007 s10072021055677 online ahead printabstractliterature data reporting sarscov2 infection multiple sclerosis ms patients recently treated immunodepleting agents cladribine alemtuzumab limited relationship iatrogenic immunodeficiency risk related sarscov2 infection severe complications still clear cautiously start immunosuppressant drugs alemtuzumab cladribine current covid19 pandemic recommended unless treatment benefits significantly outweigh potential risks report case 30yearold female ms patient infected sarscov2 virus 4 months alemtuzumab ii cycle still leukopenic lymphopenic complications also presented milder covidrelated signs symptoms compared coinfected relatives father mother partner antis1 s2 sarscov2 antibodies tested 1 month half infection resulted positive review cases reported literature sarscov2 infection ms patients treated alemtuzumab none complications severe diseasepmid34431013 doi101007 s10072021055677,0.0
small molecule screening approach encounter inefficient myelin repair curr opin pharmacol 2021 nov 6 61127135 doi 101016 jcoph202109008 online ahead printabstractwhile current multiple sclerosis therapies focused immunomodulation thereby slowing disease progression scientific interest nowadays shifted toward regenerative therapies aiming reversing already existing deficits application chemical compounds proven valuable understanding oligodendrogenesis exposing mechanisms can boost remyelination however sufficient myelin repair achieved yet thus underscoring need studies toward unmet clinical goal regard many research groups significantly contributed field via developing compound screening approaches using single substances present overview recent studies addressing identification myelin repair drugs provide insights technical aspects identified substancespmid34753035 doi101016 jcoph202109008,1.0
expert consensus narrative review management multiple sclerosis arabian gulf covid19 era focus diseasemodifying therapies vaccination covid19 neurol ther 2021 jun 17 doi 101007 s40120021002605 online ahead printabstractthis article describes consensus recommendations expert group neurologists arabian gulf region management relapsing multiple sclerosis rms covid19 era ms appears risk factor severe adverse covid19 outcomes though patients advanced disability progressive phenotype higher risk diseasemodifying therapy dmt based care appears generally safe patients ms develop covid19 although may increased risk adverse outcomes anticd20 therapy interferon teriflunomide dimethyl fumarate glatiramer acetate natalizumab cladribine tablets unlikely increase risk infection fingolimod anticd20 agents alemtuzumab may confer intermediate risk existing dmt therapy continued time patients requiring initiation dmt currently available dmts except alemtuzumab can started safely time initiate alemtuzumab subject careful individual riskbenefit considerations patients receive vaccination covid19 possible interruption existing dmtbased care need alter administration interferon teriflunomide dimethyl fumarate glatiramer acetate natalizumab fingolimod cladribine tablets vaccination new starts dmts delayed 6 weeks completion vaccination allow immune response develop doses oxford university astrazeneca vaccine may scheduled around doses anticd20 alemtuzumab white cell counts suppressed treatment allowed recover vaccinationpmid34138444 doi101007 s40120021002605,0.0
geographic differences incidence huntington#39 s disease sardinia italy neurol sci 2021 apr 1 doi 101007 s1007202105217y online ahead printabstractbackground frequency huntingtons disease hd may vary considerably higher estimates nonasian populations recently examined prevalence hd southern part sardinia large italian mediterranean island considered genetic isolate observed regional microgeographic differences prevalence hd across study area similar recently reported studies conducted european countries explore basis variability undertook study incidence hd sardinia 10year period 2009 2018methods research conducted 5 administrative areas sardinia island case patients ascertained multiple sources sardinia italyresults incidence period 53 individuals diagnosed clinically manifested hd average annual incidence rate 20092018 292 per 106 personsyear 95 ci 22 39 highest incidence rate observed south sardinia 63 95 ci 4295 rate significantly higher p001 rates cagliari oristano sassari provinces significantly differ p 038 nuoro rateconclusions overall incidence hd sardinia close correspondent estimates mediterranean countries findings highlight also possibility local microgeographic variations epidemiology hd might reflect several factors including possible founder effect rural areas south sardinia nuoropmid33792825 doi101007 s1007202105217y,0.0
retrospective claims analysis treatment patterns relapse utilization cost among patients multiple sclerosis initiating secondline diseasemodifying therapy drugs real world outcomes 2021 jun 16 doi 101007 s4080102100251w online ahead printabstractbackground realworld studies diseasemodifying therapies dmts multiple sclerosis ms reported suboptimal adherenceobjective aimed describe treatment patterns relapses healthcare resource utilization costs ms patients experiencing first observed dmt switchmethods retrospective claims database study adult patients selected ms diagnosis dmt claim study period 1 january 200931 march 2019 patients switched new dmt 1 january 2010 31 march 2018 included adherence persistence relapses allcause msrelated healthcare utilization costs reported pre postindexresults total 1554 ms patients identified mean age 46 years 74 female majority patients switched injectable dmt n 1116 718 patients generally switched oral dmt n 878 57 among patients switched dmts 460 n 715 nonadherent 42 n 645 nonpersistent 215 n 334 relapsed 12 months postswitch increase allcause msrelated healthcare costs observed pre postindex patients cost drivers included outpatient visit costs pharmacy prescriptions compared patients switched injectable dmt switched oral dmt significantly higher persistence adherence significant difference observed postindex relapse allcause msrelated total cost careconclusion low adherence poor persistence remain following initial dmt switch however patients switched oral dmts higher persistence adherencepmid34136997 doi101007 s4080102100251w,0.0
patients#39 experiences transitioning secondary progressive multiple sclerosis qualitative interviews neurol ther 2021 aug 14 doi 101007 s40120021002650 online ahead printabstractintroduction critical gaps exist understanding continuum multiple sclerosis ms progression particularly regard patient experience prior transition relapsingremitting ms rrms secondaryprogressive ms spms stages date clear diagnostic criteria determination clinical transition report use patient experience data support development qualitative conceptual model ms describes patient journey transition activerelapsing disease progressive msmethods study used singleencounter multicenter qualitative observational study design included targeted literature review individual indepth interviews adult patients clinically confirmed diagnosis spms adult care partners descriptions symptoms impacts rrms spms extracted literature review used support development interview guide conceptual modelresults participants described slow progression terms change symptoms time including development new symptoms worsening existing symptomsconclusions conceptual model transitionary period rrms spms expands current understanding progression ms patient care partner perspectivespmid34392498 doi101007 s40120021002650,0.0
gut microbiota pediatric multiple sclerosis demyelinating syndromes ann clin transl neurol 2021 dec 9 doi 101002 acn351476 online ahead printabstractobjective examine gut microbiota individuals without pediatriconset multiple sclerosis ms methods compared stoolderived microbiota canadian pediatric demyelinating disease network study participants 21 years old ms diseasemodifying drug dmd exposed nave monophasic acquired demyelinating syndrome monoads symptom onset 18 years unaffected controls 30 days without antibiotics corticosteroids v4 region 16s rna genederived amplicon sequence variants illumina miseq assessed using negative binomial regression network analyses rate ratios age sexadjusted arr results thirtytwo ms 41 monoads symptom onset mean 140 69 years 36 control participants included 75 56 58 female mean ages stool sample 165 138 151 years respectively nine ms cases 28 dmdnave although microbiota diversity alpha beta differ participants p 01 taxalevel gut community networks ms vs monoads exhibited fourfold higher relative abundance superphylum patescibacteria arr 42 95ci16112 p 0004 q 001 lower abundances shortchain fatty acid scfa producing lachnospiraceae anaerosporobacter ruminococcaceae p q 005 dmdnave ms cases depleted clostridiales vadinbb60 unnamed species versus either dmdexposed controls p q 001 monoads p 0001 q 006 exhibited altered community connectedness p 109 kruskalwallis scfaproducing taxa underrepresented consistent taxalevel findings independent us network pediatric ms centers case control n 51 42 cohort included eightfold higher abundance candidatus stoquefichus tyzzerella arr 88128 p 005 ms cases 7280 lower abundance scfaproducing ruminococcaceaenk4a214 arr 03802 p 001 interpretation gut microbiota community structure function connectivity just individual taxa likely importance mspmid34889081 doi101002 acn351476,1.0
firstline therapies late onset multiple sclerosis italian registry study eur j neurol 2021 jul 3 doi 101111 ene15006 online ahead printabstractbackground diagnosis late onset 50 years relapsing remitting multiple sclerosis lorrms increasingly described clinical practice time data focusing specific therapeutic management lorrms scarceobjective compare effectiveness injectable oral first line disease modifying therapies dmts cohort lorrms patients time first relapse time confirmed disability progression cdp additionally time discontinuationmethods multicenter observational retrospectively acquired cohort study lorrmsnave patients italian ms register started either injectable oral first line dmts january 1 2013 december 31 2017 lorrms divided two groups namely injectable group ig oral group og cox models adjusted inverse probability weighted propensity score built investigated outcomesresults cohort 3 989 patients 302 enrolled 203 ig 99 og two cohorts differ baseline characteristics time first relapse show difference two groups hr 110 ci 95 050246 p797 furthermore differences found two groups respect risk cdp hr 104 ci 95 035306 p 939 risk dmt discontinuation hr 090 ci 95 017208 p 425 conclusions realworld data italian ms register suggested injectables oral first line dmts controlled similarly investigated outcomes lorrmspmid34216532 doi101111 ene15006,0.0
sphingosine kinase 2 essential remyelination following cuprizone intoxication glia 2021 aug 16 doi 101002 glia24074 online ahead printabstracttherapeutics promote oligodendrocyte survival remyelination needed restore neurological function demyelinating diseases sphingosine 1phosphate s1p essential lipid metabolite signals five gprotein coupled receptors s1p receptor agonists fingolimod valuable immunosuppressants used treat multiple sclerosis promote oligodendrocyte survival however role endogenous s1p synthesized enzyme sphingosine kinase 2 sphk2 oligodendrocyte survival myelination established study investigated requirement sphk2 oligodendrocyte survival remyelination using cuprizone mouse model acute demyelination followed spontaneous remyelination oligodendrocyte density differ untreated wildtype wt sphk2 knockout sphk2 mice however cuprizone treatment caused significantly greater loss mature oligodendrocytes sphk2 compared wt mice following cuprizone withdrawal spontaneous remyelination occurred wt sphk2 mice even though progenitor mature oligodendrocyte density increased genotypes levels cytotoxic sphingosine ceramide higher corpus callosum sphk2 mice contrast wt mice decline following cuprizone withdrawal sphk2 mice also observed significant reduction myelin thickness aging sphk2 compared wt mice results provide first evidence sphk2 dominant enzyme catalyzing s1p synthesis adult brain essential remyelination following demyelinating insult myelin maintenance aging propose persistently high levels sphingosine ceramide direct consequence sphk2 deficiency may block remyelinationpmid34399014 doi101002 glia24074,1.0
alemtuzumab treatment denmark national study based danish multiple sclerosis registry mult scler 2021 mar 2913524585211003291 doi 101177 13524585211003291 online ahead printabstractobjective investigate clinical outcomes realworld setting complete populationbased cohort alemtuzumabtreated ms patients denmarkmethods data retrieved danish multiple sclerosis registry 2009 2019 demographic diseasespecific patient parameters related treatment history efficacy safety outcomes assessed baseline followup visitsresults total 209 patients 78 female started treatment alemtuzumab study period 31 14 years followup 2 years 75 patients relapsefree compared 48 year alemtuzumab p 0001 annual number relapses reduced 69 year 4 compared year prior alemtuzumab active disease alemtuzumab increased annual hazard rate relapse hr 288 p 0001 expanded disability status scale edss score remained stable improved 81 patients 2 years need additional treatment course associated higher number relapses year alemtuzumab odds ratio 195 p 0001 conclusion country primarily escalation strategy relapse rate reduction maintained 5 years edss stabilized improved majority patients higher relapse rate 1 year alemtuzumab increased odds additional courses novel serious aes observedpmid33779361 doi101177 13524585211003291,0.0
nucleus basalis meynert damage cognition patients multiple sclerosis j neurol 2021 may 16 doi 101007 s00415021105947 online ahead printabstractbackground nucleus basalis meynert nbm representing major source cerebral cholinergic innervations vulnerable neurodegeneration alzheimers parkinsons diseaseobjective determine associations nbm properties cognitive outcomes patients multiple sclerosis pwms methods 84 pwms 19 controls underwent 3t mri paced auditory serial addition test pasat subtests brief international cognitive assessment ms bicams nbm volume fractional anisotropy mean diffusivity md axial diffusivity radial diffusivity d calculated analyses assessed relationships cognition nbm measures linear regressions evaluated prognostic value baseline measures predicting cognitive change 3 years followup n 67 results cognitive tests correlated nbm diffusivity pwms range r 029 r 040 p 005 accounting nbm volume nbm md d explained additional variance adjusted r2 range 008020 p 005 correlations nbm imaging metrics cognitive tests remained significant including imaging parameters cognitive key brain regions models controlling age education baseline cognitive test score nbm measures predicted change cognition followup 5 10 2 10 assessments relapsingremitting sample n 43 adjusted r2 range 023 038 p 005 secondary progressive sample adjusted r2 0280 0183 respectivelyconclusions nbm damage linked cognitive impairment pwmspmid33997915 doi101007 s00415021105947,0.0
corona pandemic multiple sclerosis vaccinations implications patientspart 1 recommendations nervenarzt 2021 jul 7 doi 101007 s00115021011554 online ahead printabstractthe ongoing covid19 pandemic global health crisis new challenges constantly emerging especially healthcare system least emergence various viral mutations given variety immunomodulatory immunosuppressive therapies multiple sclerosis ms immense developments vaccine production high need information people ms aim article therefore provide overview ms covid19 well clarify implications patients ms especially regarding vaccination formulate appropriate recommendationspmid34232359 doi101007 s00115021011554,1.0
magnetic resonance imaging neuromyelitis optica spectrum disorder clin exp immunol 2021 jun 2 doi 101111 cei13630 online ahead printabstractneuromyelitis optica spectrum disorder nmosd inflammatory disease central nervous system cns associated antibodies aquaporin4 aqp4 distinct clinical radiological pathological features also overlap multiple sclerosis mogantibody associated disease early recognition nmosd important differing responses acute preventive therapy magnetic resonance mr imaging proven essential process key mr imaging clues diagnosis nmosd longitudinally extensive lesions optic nerve half length spinal cord 3 vertebral segments bilateral optic nerve lesions lesions optic chiasm area postrema floor iv ventricle periaqueductal grey matter hypothalamus walls iii ventricle nmosd specific lesions denoted unique morphology heterogeneous lesions corpus callosum cloudlike gdenhancing white matter lesions bright spotty lesions spinal cord lesions described nmosd including linear periventricular periependymal lesions patch subcortical white matter lesions may less specific use advanced mr imaging techniques yielding useful information focal degeneration thalamus optic radiation nmosd suggests paramagnetic rim patterns changes normal appearing white matter specific ms mr imaging crucial early recognition nmosd directing testing aqp4 antibodies guiding immediate acute treatment decisions increasingly mr imaging playing role diagnosing seronegative cases nmosdpmid34080180 doi101111 cei13630,0.0
suppression experimental autoimmune encephalomyelitis igg fc fragments bearing regrf epitopes int immunopharmacol 2021 oct 31 101 pt 108309 doi 101016 jintimp2021108309 online ahead printabstractpreviously identified rheumatoid factor production provides rats resistance experimental autoimmune diseases named regulatory rheumatoid factor regrf immunization conformers igg fc fragments carrying epitopes specific regrf reduces rat collageninduced arthritis aim study determine whether igg fc fragments bearing regrf epitopes suppress experimental autoimmune encephalomyelitis evaluate potential strategy stimulating production regrf treat multiple sclerosis two days myelin basic protein injection rats immunized fc fragments exhibiting regrf epitopes well fc fragments without epitopes effect fc immunization clinical signs eae immunological parameters evaluated stimulation regrf production igg fc fragments bearing regrf epitopes diminished eae symptoms rats immunization fc fragments without epitopes worsened eae improvement eae symptoms rats treated fc fragments bearing regrf epitopes associated regrf production relatively low number blood cd4 t lymphocytes disease development experiments involving immunizing intact rats lymph node mononuclear cell cultures fc fragments bearing regrf epitopes decreased cd4 t lymphocyte population indirectly via regrf production regrf promising biotarget ms fc fragments bearing regrf epitopes potential therapeutic agent mspmid34731688 doi101016 jintimp2021108309,1.0
clinical characteristics classification management adult nasopharyngolaryngeal hemangioma laryngoscope 2021 jun 23 doi 101002 lary29703 online ahead printabstractobjectives hypothesis analyze clinical features classification treatment adult nasopharyngolaryngeal hemangioma anplh study design retrospective studymethods february 2009 may 2020 101 patients anplh reviewed analyzedresults symptoms anplh frequently displayed abnormal pharyngeal sensation functional defection according lesion location anplh divided five categories including nasopharyngeal oropharyngeal hypopharyngeal laryngeal mixed types mixed type constitutes highest portion nasopharyngeal type least cohort lesions resect natural cavity endoscopy patients mixed lesions higher rate postoperative recurrence planned multiple surgeries acceptable severe intraoperative postoperative complications occurred patient cohortconclusions patients anplh always symptomatic even functional defective can classified five categories based lesion location patients endoscopic surgery natural cavity recommended remove lesions fewer complications favorable clinical outcomeslevel evidence 4 laryngoscope 2021pmid34160868 doi101002 lary29703,0.0
treatment 25hydroxyvitamin d3 calcifediol associated reduction blood neutrophiltolymphocyte ratio marker disease severity patients hospitalized covid19 pilot multicenter randomized placebocontrolled double blind clinical trial endocr pract 2021 oct 12s1530891x 21 012593 doi 101016 jeprac202109016 online ahead printabstractobjective goal randomized placebocontrolled clinical trial investigate therapeutic efficacy oral 25hydroxyvitamin d3 25 oh d3 improving vitamin d status vitamin d deficient insufficient patients infected sarscov2 covid19 virusmethods multicenter randomized double blinded randomized placebocontrolled clinical trial participants recruited three hospitals affiliated institution blinded review institution blinded review results total 106 hospitalized patients circulating concentration 25 oh d 30 ng ml enrolled study within 30 60 days 794 26 34 100 24 24 patients received 25 oh d3 became sufficient whereas 125 patients placebo group became sufficient 2 months followup observed overall lower trend hospitalization icu duration needing ventilator assistance mortality 25 oh d3 group compared placebo group werent statistically significant treatment oral 25 oh d3 associated significant increase lymphocyte percentage decrease ratio neutrophils lymphocytes nlr patients lower nlr significant associated reduced icu admission days mortalityconclusion analysis indicated oral 25hydroxyvitamin d3 able correct vitamin d deficiency insufficiency covid19 patients resulted improved immune function increasing blood lymphocyte percentage rcts larger sample size higher dose 25 oh d3 maybe needed confirm potential effect 25 oh d3 reducing clinical outcomes covid19 patientsethics dissemination study protocol approved ethics committee institution blinded review approval number irtumsvcrrec1399061 dissemination plans include academic publications conference presentations social mediatrial registration protocol registered iranian registry clinical trials irct april 11 2020 number blinded review us national institutes health number blinded review may 11 2020pmid34653608 doi101016 jeprac202109016,0.0
predictive value sub classification focal segmental glomerular sclerosis oxford classification iga nephropathy ann med 2021 dec 53 1 587595 doi 101080 0785389020211897664abstractbackground oxford classification iga nephropathy igan revised 2016 lacked sufficient evidence prognostic value subclassification focal segmental glomerular sclerosis s lesion proper proportion s lesion subclassification remains undeterminedaim study aimed explore predictive value new subclassification s score renal outcomes igan patientsmethods 348 patients iganassociated s lesion enrolled according optimal cutoff 25 established receiver operating characteristic roc curves divided s1 patients two groups s1a group s lesion 25 s1b group s lesion 25 igan patients mild lesion m0e0s0t0c0 set control group clinical features renal biopsy pathological findings followup parameters followup time ranged 1 5 years collected used univariate multivariate analyses assess whether subclassification s score refine risk prediction clinical utilityresults demonstrated s lesion 25 associated rapid gfr loss lower rate complete remission proteinuria even adjusted multiple clinic pathological variables compared s1a group p values 05 ratio glomeruli t lesion crescents higher patients s lesion 25 data showed igan patients s lesion 25 increased risk poor renal outcomes even immunosuppressionconclusion study might recommend new subclassification s scores s0 s lesion s1 s lesion 25 glomeruli s2 s lesion 25 glomeruli oxford classification model may also help evaluate pros cons immunosuppressive therapy igan patients different level s lesionkey messagess lesion 25 independent risk factor poor renal outcome igan patientsthis new subclassification s scores may help evaluate pros cons immunotherapy igan patients different level s lesionpmid33825605 doi101080 0785389020211897664,0.0
lipoic acid supplementation associated neural epidermal growth factorlike 1 nell1 associated membranous nephropathy kidney int 2021 oct 15s00852538 21 009467 doi 101016 jkint202110010 online ahead printabstractlipoic acid alpha lipoic acid thioctic acid popular overthecounter antioxidant insulinmimetic supplement investigation variety conditions including multiple sclerosis diabetes schizophrenia unfortunately highgrade proteinuria unexpected adverse event specific treatment arm clinical trial investigating lipoic acid supplementation patients multiple sclerosis observation led detection similar patients nephrology practice describe four biopsyproven cases neural epidermal growth factorlike 1 nell1 associated membranous nephropathy following lipoic acid supplementation fifth suspected case discontinuation lipoic acid supportive therapy resulted remissionpmid34662650 doi101016 jkint202110010,0.0
diagnosis multiple sclerosis using multifocal erg data feature fusion inf fusion 2021 dec 76157167 doi 101016 jinffus202105006abstractthe purpose paper implement computeraided diagnosis cad system multiple sclerosis ms based analysing outer retina assessed multifocal electroretinograms mfergs mferg recordings taken retiport scan 21 roland consult device 15 eyes patients diagnosed incipient relapsingremitting ms without prior optic neuritis 6 eyes control subjects selected mferg recordings grouped whole macular visual field five rings four quadrants group correlation normative database adaptively filtered signals based empirical model decomposition emd three features continuous wavelet transform cwt domain obtained initial 40 features 4 relevant selected two stages using filter method b using wrapperfeature selection method support vector machine svm used classifier optimal cad configuration matthews correlation coefficient value 089 accuracy 095 specificity 10 sensitivity 093 obtained study identified outer retina dysfunction patients recent ms analysing outer retina responses mferg employing svm classifier conclusion promising new electrophysiologicalbiomarker method based feature fusion ms diagnosis identifiedpmid34867127 pmcpmc8475498 doi101016 jinffus202105006,0.0
correction gray matter atrophy corticostriatalthalamic network sensorimotor network relapsingremitting primary progressive multiple sclerosis neuropsychol rev 2021 apr 8 doi 101007 s11065021095036 online ahead printno abstractpmid33830412 doi101007 s11065021095036,0.0
maternal intake restriction programs energy metabolism clock circadian regulator mtor signals skeletal muscles goat offspring probably via protein kinase acampresponsive elementbinding proteins pathway anim nutr 2021 dec 7 4 13031314 doi 101016 janinu202109006 epub 2021 oct 6abstractthe biological mechanism maternal undernutrition increases metabolic disorder risk skeletal muscles offspring fully understood hypothesize maternal intake restriction influences metabolic signals skeletal muscles offspring via glucagonmediated pathway twentyfour pregnant goats assigned control group 100 nutrients requirement n 12 restricted group 60 control feed allowance pregnant days 45 100 n 12 blood l ongissimus thoracis muscle sampled dams 100 d gestation fetuses 100 d gestation kids 90 d birth group data analyzed using linear mixed model multiple comparison method sidak applied intake restriction reduced p 005 total blood protein dams fetuses maternal restriction decreased p 005 campresponsive elementbinding protein 1 creb1 crebbinding protein crebbp protein kinase pka aryl hydrocarbon receptor nuclear translocatorlike protein 1 bmal1 protein kinase b akt1 mammalian target rapamycin mtor regulatoryassociated protein mtor rptor mrna expression fetuses reduced p 005 crebbp nuclear receptor subfamily 1 group h member 3 nr1h3 dbox binding par bzip transcription factor dbp pka mrna levels kids increased p 005 peroxisome proliferatoractivated receptor gamma coactivator 1 alpha pgc1 tuberous sclerosis 2 tsc2 mrna levels fetuses mrna expression clock circadian regulator clock tsc2 genes increased p 005 restricted kids protein expression total pka phosphorylated pka restricted fetuses kids downregulated p 005 protein expression total mtor phosphorylated mtor reduced p 005 restricted fetuses kids maternal intake restriction regulated fat oxidation protein synthesis circadian clock expression muscles offspring probably via glucagonmediated pkacreb pathway reveals noteworthy molecular pathway maternal undernutrition leads metabolic adaptation skeletal muscle offspringpmid34786503 pmcpmc8567324 doi101016 janinu202109006,0.0
efficacy gamma knife radiosurgery management multiple sclerosisrelated trigeminal neuralgia systematic review metaanalysis neurosurg rev 2021 feb 20 doi 101007 s10143021015073 online ahead printabstracttrigeminal neuralgia tn frequent craniofacial pain condition commonly affects patients suffering multiple sclerosis ms stereotactic radiosurgery especially gamma knife radiosurgery gkrs represents safe effective treatment tn adopted also mstn lower success rate therefore aimed analyze outcome gkrs mstn pubmed web science google scholar reference list relevant articles searched gkrs mstn two investigators independently identified articles assessed study quality extracted data endpoints interest initial pain responders successful treatments end followup factors influencing outcome data analyses performed using r software twelve articles involving 646 patients met inclusion criteria pooled proportion patients experienced initial response gkrs treatment 83 ci 7490 cumulative proportion successful treatments end followup 47 ci 3360 variables found significant contribution heterogeneity regarding initial response outcome variable significantly explaining heterogeneity found proportion successful treatments length followup negative b coefficient 00051 p value 00047 regarding efficacy gkrs mstn initial pain response rate 83 dramatically decreases 47 followup gkrs still represents valuable option mstn however longterm efficacy always consideredpmid33611721 doi101007 s10143021015073,0.0
healthrelated quality life narcolepsy systematic review metaanalysis j sleep res 2021 may 25e13383 doi 101111 jsr13383 online ahead printabstractto date systematic analysis literature regarding healthrelated quality life narcolepsy systematic review aimed examine impact narcolepsy healthrelated quality life measured standardised healthrelated quality life questionnaires short form 36 functional outcome sleep questionnaire following databases medline embase cinahl web science searched studies investigated healthrelated quality life adults narcolepsy studies reviewed independently two reviewers randomeffects metaanalysis performed total 30 studies eligible inclusion review additionally metaanalyses conducted short form 36 eq5d short form 36 metaanalysis identified pooled mean scores physical component summary 4591 less affected mental component summary 4298 people narcolepsy experience substantially lower healthrelated quality life compared general population norms usa uk france norway well compared people chronic diseases multiple sclerosis diabetes hypertension epilepsy research warranted identify longitudinal effects narcolepsy healthrelated quality life develop narcolepsyspecific healthrelated quality life toolpmid34036640 doi101111 jsr13383,0.0
remyelination neuroprotective effects alemtuzumab therapy patients multiple sclerosis j neurol neurosurg psychiatry 2021 oct 19jnnp2021326821 doi 101136 jnnp2021326821 online ahead printno abstractpmid34667100 doi101136 jnnp2021326821,1.0
neurological update cognitive rehabilitation multiple sclerosis j neurol 2021 may 24 doi 101007 s00415021106182 online ahead printabstractcognitive impairment common debilitating symptom multiple sclerosis ms limited evidence diseasemodifying therapies effective treating cognitive dysfunction cognitive rehabilitation promising approach treat cognitive dysfunction ms gaining empirical support last 10 years current review will provide brief overview cognitive rehabilitation ms overall evidence cognitive rehabilitation programs either restorative compensatory efficacious treating msrelated cognitive dysfunction clinicians consider lowcost lowrisk yet effective treatment approach patientspmid34028615 doi101007 s00415021106182,1.0
anticd20 therapy corrects cd8 regulatory t cell deficit multiple sclerosis mult scler 2021 mar 3013524585211003301 doi 101177 13524585211003301 online ahead printabstractobjective determine effect longterm anticd20 bcelldepleting treatment regulatory t cell immune subsets subnormal untreated ms patientsmethods 30 clinically stable ms patients 38 months ocrelizumab treatment compared 13 healthy controls 29 therapynave ms 9 interferontreated ms 3 rituximabtreated ms 3 rituximabtreated patients autoimmune inflammatory diseases cd8 cd28 cd4 foxp3 expression peripheral blood mononuclear cells quantitated flow cytometryresults cd8+ cd28 regulatory cells rose onethird healthy control levels ocrelizumab treatment 268 vs 798 normalized 12 months 135 rose 24fold healthy controls 18 months ocrelizumab therapy 190 cd4+ foxp3+ regulatory cells lower ms healthy controls 798 showed slight longterm decreases ocrelizumab cd8+ cd28 cd4+ foxp3+ regulatory t cell percentages ifntreated ms patients untreated ms healthy controlsinterpretation longterm treatment ocrelizumab markedly enriches cd8+ cd28 regulatory t cells corrects low levels seen ms treatment slightly decreasing cd4+ foxp3+ regulatory t cells homeostatic enrichment regulatory cd8 t cells provides mechanism addition b cell depletion benefits anticd20 treatment mspmid33783270 doi101177 13524585211003301,0.0
cognitive impairment central vein sign paramagnetic rim lesions ris mult scler 2021 mar 2313524585211002097 doi 101177 13524585211002097 online ahead printabstractobjective central vein sign cvs paramagnetic rim lesions prl emerging imaging biomarkers multiple sclerosis ms reflecting perivenular demyelination chronic smoldering inflammation objective study assess relationships cognitive impairment ci cvs prl radiologically isolated syndrome ris methods twentyseven adults ris underwent 30 t mri brain cervical spinal cord sc cognitive assessment using minimal assessment cognitive function ms battery cvs prl assessed whitematter lesions wmls t2weighted segmented echoplanar magnitude phase images multivariable linear regression evaluated relationships ci mri measuresresults global ci present 9 33 participants processing speed visual memory frequently affected participants 93 40 cvs + wml threshold distinguishing ms wm disorders 63 demonstrated prl linear regression revealed cvs + wml predicted performance verbal memory 0024 p 003 prl predicted performance verbal memory 0040 p 004 processing speed 0039 p 003 conclusions ci common ris associated markers perivenular demyelination chronic inflammation wml cvs + wml prl prospective followup cohort will ascertain importance ci cvs prl risk factors conversion ris mspmid33754887 doi101177 13524585211002097,1.0
hope patients neuromyelitis optica spectrum disorders mechanisms trials nat rev neurol 2021 oct 28 doi 101038 s41582021005688 online ahead printabstractneuromyelitis optica spectrum disorder nmosd rare inflammatory cns disease primarily manifests relapsing episodes severe optic neuritis myelitis diagnosis nmosd supported detection igg autoantibodies target aquaporin 4 aqp4 water channel cns astrocytespecific protein aqp4 antibody binding leads aqp4 internalization complementdependent antibodydependent cellular cytotoxicity water channel dysfunction cumulative attackrelated injury causes disability nmosd prevention attacks expected prevent disability accrual recently regulatorapproved therapies available nmosd traditional immunosuppressant therapies including mycophenolate mofetil azathioprine rituximab widely used benefits assessed controlled studies 2019 2020 five phase ii iii randomized placebocontrolled trials four mechanismbased therapies nmosd published demonstrated four effectively prolonged time first relapse four drugs monoclonal antibodies complement c5 antibody eculizumab il6 receptor antibody satralizumab b celldepleting antibody inebilizumab targets cd19 rituximab targets cd20 review pathophysiology nmosd rationale development mechanismbased drugs methodology outcomes five trials implications findings treatment nmosdpmid34711906 doi101038 s41582021005688,0.0
effect sodium channels neurological#x2f neuronal disorders systematic review int j dev neurosci 2021 oct 22 doi 101002 jdn10153 online ahead printabstractneurological neuronal disorders associated structural biochemical electrical abnormalities nervous system many neurological diseases yet discovered interventions used treatment disorders include avoidance measures lifestyle changes physiotherapy neurorehabilitation pain management medication surgery sodium channelopathies alterations structure expression function voltagegated sodium channels vgscs considered causes neurological neuronal diseases online databases including scopus science direct google scholar pubmed assessed studies published 1977 2020 using keywords review sodium channels blocker neurological diseases neuronal diseases vgscs consist one subunit two subunits subunits known regulate gating kinetics functional characteristics localization ion channel channels involved cell migration cellular connections neuronal pathfinding neurite outgrowth vgsc action potential triggered propagated neurons action potentials physiological functions passage impermeable ions electrophysiological properties channels relationship neurological neuronal disorders identified subunit mutations involved development diseases epilepsy multiple sclerosis autism alzheimers disease accordingly conducted review link vgscs neurological neuronal diseases also novel therapeutic targets introduced future drug discoveriespmid34687079 doi101002 jdn10153,0.0
factor xii inhibitors review patent literature expert opin ther pat 2021 jun 18 doi 101080 1354377620211945580 online ahead printabstractintroduction blood coagulation factor xii fxii emerging potentially safe drug target dysregulation associated thrombosis hereditary angioedema neuro inflammation time fxiideficiency practically asymptomatic industrial academic institutions developed number potential therapeutic agents targeting either fxii zymogen active form fxiia treatment thrombotic inflammatory conditions associated activity enzymeareas covered short overview fxii structure function underlining suitability drug target given article reviews patents reported last three decades fxii targeting therapeutic agents agents include small molecules proteins peptides oligonucleotides sirnas monoclonal antibodiesexpert opinion performed analysis patents revealed many fxii inhibitors early preclinical stage several already showed efficacy vivo animal models thrombosis sepsis hereditary angioedema multiple sclerosis two antifxiia agents namely tick protein ircpi monoclonal antibody csl312 currently human clinical trials results trials studies fxii pathophysiological functions will encourage development new fxii inhibitorspmid34142629 doi101080 1354377620211945580,0.0
yoga interventions used rehabilitation stroke parkinson#39 s disease multiple sclerosis scoping review clinical research j altern complement med 2021 jun 29 doi 101089 acm20210003 online ahead printabstractobjectives current body literature reviewed compile describe yoga interventions applied clinical research neurologic rehabilitation settings patients affected stroke parkinsons disease pd multiple sclerosis ms design available literature yoga therapy yt mapped following fivestage framework identify key concepts knowledge gaps evidence inform practice publications identified medline cinahl embase psycinfo selected studies required subjects clinical diagnosis stroke pd ms participate yoga intervention physical cognitive psychosocial outcome measures assessed results total 50 studies included review study characteristics patient demographics description yoga intervention reported outcome measures main findings extracted studies conclusion implementing yt neurorehabilitation can help health care professionals integrate holistic approach addresses fundamental physical psychological challenges living chronic debilitating neurologic disorder included studies described yogic interventions consisting group individual therapy sessions lasting 6075 min carried one three times per week 812 consecutive weeks across three conditions studies described scoping review used different yoga protocols confirming lack specific interventional parameters available implementing yoga rehabilitation individuals affected stroke pd mspmid34185577 doi101089 acm20210003,0.0
people multiple sclerosis receive appropriate support national disability insurance scheme matching level disability description disease #39 burden societal cost people multiple sclerosis australia aust health rev 2021 sep 21 doi 101071 ah21056 online ahead printabstractobjectivethis study first assess national disability insurance scheme ndis package allocated people multiple sclerosis pwms correlated disability level measured standardised neurological assessmentmethodswe aimed recruit 10 pwms per expanded disability status score edss step including edss 0 disability 9 bedridden requested information ndis application value packages compared mobility cognition psychological impactresultsout 186 pwms 49 patients ndis package approved mean values annual allowance au30318 patients mild disability au38361 moderate disability au115113 severe disability striking variability packages approved restricted mobility seems driving factor rejection rates 20 patients mild moderate disability none severe disability package value correlated edss steps cognitive impairment physical impact psychological impactconclusionsthis first study assess ndis packages correlate internationally accepted disability scales ndis support correlated disability measured edss steps cognition psychological impact diseasewhat known topicthere 25000 australians living multiple sclerosis one common neurological diseases leading disability early age national disability insurance scheme introduced since 2013 particularly assist young disabled australians participate community whether approved package correlates internationally accepted disability scores yet assessedwhat paper addthis study first correlate disability assessed expanded disability severity scale edss approved package valuewhat implications practitionersmultiple sclerosis variable disease affecting quality life due impairment mobility also cognition mental health although ndis package value correlated edss cognition psychological impact disease often neglectedpmid34543604 doi101071 ah21056,0.0
metformin therapy attenuates proinflammatory microglia inhibiting nfkappab cuprizone demyelinating mouse model multiple sclerosis neurotox res 2021 sep 27 doi 101007 s1264002100417y online ahead printabstractmultiple sclerosis ms chronic disorder characterized reactive gliosis inflammation demyelination microglia plays crucial role pathogenesis ms dynamic plasticity polarize proinflammatory m1 antiinflammatory m2 phenotypes metformin glucoselowering drug attenuates inflammatory responses activating adenosine monophosphate protein kinase ampk suppresses nuclear factor kappa b nfb study indirectly investigated whether metformin therapy regulate microglia activity cuprizone cpz induced demyelination mouse model ms via measuring markers associated pro antiinflammatory microglia evaluation myelin luxol fast blue staining revealed metformin treatment cpz + met diminished demyelination comparison cpz mice addition metformin therapy significantly alleviated reactive microgliosis astrogliosis corpus callosum measured iba1 gfap staining moreover metformin treatment significantly downregulated expression proinflammatory associated genes inos h2aa tnf corpus callosum whereas expression antiinflammatory markers arg1 mrc1 il10 promoted compared cpz mice furthermore protein levels inos proinflammatory marker significantly decreased metformin group trem2 antiinflammatory marker increased addition metformin significantly increased ampk activation cpz mice finally metformin administration significantly reduced activation level nfb cpz mice summary data revealed metformin attenuated proinflammatory microglia markers suppressing nfb activity positive effects metformin microglia remyelination suggest used promising candidate lessen incidence inflammatory neurodegenerative diseases mspmid34570348 doi101007 s1264002100417y,1.0
hydroxychloroquine primary progressive multiple sclerosis ann neurol 2021 sep 30 doi 101002 ana26239 online ahead printabstractobjective primary progressive multiple sclerosis ppms respond well immunomodulatory immunosuppressive treatment chronic activation microglia implicated pathophysiology ppms antimalarial drug hydroxychloroquine hcq reduces activity human microglia neuroprotective effects vitromethods conducted singlearm phase 2 futility trial 200mg oral hcq twice daily 18 months effort investigate disability worsening absence overt focal inflammation excluded participants contrast enhancing lesions screening mri primary endpoint 20 worsening timed 25foot walk measured 6 18 months followupresults based original trial data 40 cohort expected worsen used simon twostage design compare null hypothesis 40 cohort worsening onesided alternative 20 using 5 type 1 error rate 80 power hcq treatment deemed successful fewer 10 35 participants experienced clinically significant worsening study met primary endpoint 8 35 participants worsened 6 18 months hcq overall well tolerated adverse events 82 serious adverse events 12 participants serious adverse events unlikely related hcq useinterpretation hcq treatment associated reduced disability worsening people ppms hcq promising treatment candidate ppms investigated randomized controlled clinical trials clinicaltrialsgov identification nct02913157 article protected copyright rights reservedpmid34590328 doi101002 ana26239,1.0
evidence glutamine synthetase function mouse spinal cord oligodendrocytes glia 2021 aug 15 doi 101002 glia24071 online ahead printabstractglutamine synthetase gs key enzyme metabolizes glutamate glutamine gs highly enriched astrocytes expression glial lineages noted using combination reporter mice cell typespecific markers show gs expressed myelinating oligodendrocytes ol oligodendrocyte progenitor cells mouse human ventral spinal cord investigate role gs mature ol used conditional knockout cko approach selectively delete gsencoding gene glul ol caused significant decrease glutamine levels mouse spinal cord extracts gs cko mice cnpcre+ glulfl fl showed differences motor neuron numbers size axon density ol differentiation myelination ventral spinal cord normal 6 months age interestingly gs cko mice showed transient specific decrease peak force locomotion motor coordination remained unaffected last gs expression ol increased chronic pathological conditions mouse humans found diseasestage dependent increase ol expressing gs ventral spinal cord sod1 g93a mouse model amyotrophic lateral sclerosis moreover showed glul transcripts levels increased ol leukocortical tissue multiple sclerosis control patients findings provide evidence towards olencoded gs function spinal cord sensorimotor axis dysregulated chronic neurological diseasespmid34396578 doi101002 glia24071,1.0
targeted deletion pac1 receptors retinal neurons enhances neuron loss axonopathy model multiple sclerosis optic neuritis neurobiol dis 2021 oct 2105524 doi 101016 jnbd2021105524 online ahead printabstractchronic inflammation drives synaptic loss multiple sclerosis ms also commonly observed neurodegenerative diseases clinically approved treatments ms provide symptomatic relief fail halt neurodegeneration neurological decline studies animal disease models demonstrated neuropeptide pituitary adenylate cyclaseactivating polypeptide pacap adcyap1 exhibits antiinflammatory neuroprotective regenerative properties antiinflammatory actions appear mediated primarily two receptors vpac1 vpac2 also bind vasoactive intestinal peptide vip pharmacological experiments indicate another receptor pac1 adcyap1r1 highly selective pacap provides protection neurons although genetic evidence mechanistic information lacking determine pac1 receptors protect neurons cellautonomous manner used adenoassociated virus aav2 deliver cre recombinase retina mice harboring floxed pac1 alleles mice subjected chronic experimental autoimmune encephalomyelitis eae disease model recapitulates major clinical pathological features ms associated optic neuritis unexpectedly deletion pac1 nave mice resulted deficit retinal ganglionic neurons rgns dendrites suggesting homeostatic role pac1 moreover deletion pac1 resulted increased eaeinduced loss subpopulation rgns purported vulnerable animal models glaucoma increased axonal pathology increased secondary presence microglia macrophages also prominently seen optic nerve findings demonstrate neuronal pac1 receptors play homeostatic role protecting rgns directly protects neurons axons neuroinflammatory challenge significance statement chronic inflammation major component neurodegenerative diseases plays central role multiple sclerosis ms current treatments ms prevent neurodegeneration neurological decline neuropeptide pituitary adenylate cyclaseactivating polypeptide pacap shown antiinflammatory neuroprotective regenerative properties cell type receptorspecific mechanisms clear test whether protective effects pacap direct pac1 receptor subtype neurons delete pac1 receptors neurons investigate neuropathologigical changes animal model ms findings demonstrate pac1 receptors neurons play homeostatic role maintaining neuron health can directly protect neurons axons neuroinflammatory diseasepmid34610465 doi101016 jnbd2021105524,1.0
prenatal sirolimus treatment rhabdomyomas tuberous sclerosis pediatr neurol 2021 sep 25 1252631 doi 101016 jpediatrneurol202109014 online ahead printabstractbackground tuberous sclerosis cardiac rhabdomyomas regress spontaneously cases tumors can cause lifethreatening hemodynamic compromise requiring subsequent surgical resection mechanistic target rapamycin inhibitors everolimus sirolimus shown effective treatments multiple conditions four reports offlabel treatment transplacental sirolimus fetal rhabdomyomas due tuberous sclerosis complex optimal dosing regimen unknownmethods reviewed medical records patients treated prenatally sirolimus rhabdomyomas fetuses clinical molecular diagnosis tuberous sclerosis complex 2012 consensus diagnostic criteria including positive genetic test clinical history mechanistic target rapamycin inhibitor dosing levels outcome adverse events reviewed initiation sirolimus treatmentresults three fetuses treated maternal sirolimus dosing regimens subsequent trough levels differed 1 mg day 6 mg day 10 ng ml 122 ng ml cardiac rhabdomyomas gradually shrank patients growth restriction noted one patient severe adverse events occurred treatment periodconclusions maternal sirolimus appears safe treatment option prenatally detected rhabdomyomas possible need intervention followup visits fetal ultrasound echocardiography laboratory work performed weekly treatment period optimal dosing trough level timepoints remain unclear based results recommend sirolimus starting dose least 2 mg m2 day preferably 335 mg m2 day achieve target trough level 1012 ng mlpmid34624607 doi101016 jpediatrneurol202109014,0.0
multiple sclerosis covid19 vaccines making point neurol ther 2021 oct 8 doi 101007 s40120021002887 online ahead printabstracton 11 march 2020 world health organization declared coronavirus disease 19 covid19 outbreak pandemic context several studies clinical trials conducted since many currently ongoing leading development several covid19 vaccines different mechanisms action people affected multiple sclerosis ms considered highrisk subjects countries prioritized covid19 vaccination however management ms covid19 pandemic represented new challenge ms specialists particularly initial lack guidelines differing recommendations despite initial hesitation prescribing diseasemodifying drugs dmds nave already treated patients ms national neurology associations organizations agree stopping treatment however care needed especially patients treated immunedepleting drugs also require attentions programming vaccine administration many discoveries new research results accumulated short time covid19 resulting need summarizing existing evidence topic review describe latest research results immunological aspects sarscov2 infection speculating impact covid19 vaccines mechanisms action focused management ms covid pandemic according recent guidelines recommendations finally efficacy covid19 wellknown vaccines infectious disease patients ms dmds discussedpmid34625925 doi101007 s40120021002887,0.0
cns atrophy predicts future dynamics disability progression realworld multiple sclerosis cohort eur j neurol 2021 sep 6 doi 101111 ene15098 online ahead printabstractbackground era individualized multiple sclerosis ms patient management biomarkers accurate prediction future clinical outcomes needed aimed evaluate potential shortterm mri atrophy measures serum neurofilament light chain snfl predictors dynamics disability accumulation relapseonset msmethods brain gray white matter thalamic striatal pallidal cervical spinal cord volumes lesionload measured three available time points mean timespan 224070 years 183 patients 140 relapsingremitting rrms 43 secondaryprogressive spms 123 female age 464110 years disease duration 15793 years respective annual changes calculated baseline snfl also measured third available timepoint patient subsequently patients received annual clinical examinations 5437 years including expanded disability status scale edss ninehole peg test timed 25foot walk testresults higher annual spinal cord atrophy rates lesionload increase predicted higher future expanded disability status scale worsening time spms lower baseline thalamic volumes predicted higher walkingspeed worsening time rrms lower baseline gray matter well higher white matter spinal cord atrophy rates lesionload increase baseline striatal volumes baseline snfl predicted higher future handdexterity worsening time models showed reasonable high prediction accuracyconclusion study demonstrates capability shortterm mri metrics accurately predict future dynamics disability progression realworld relapseonset ms cohort current work represents step towards utilization structural mrimeasurements patient carepmid34487400 doi101111 ene15098,0.0
microstructural white matter alterations cognitively impaired patients early stages multiple sclerosis clin neuroradiol 2021 mar 31 doi 101007 s00062021010108 online ahead printabstractpurpose conventional quantitative magnetic resonance imaging mri parameters weakly associated cognitive impairment ci early multiple sclerosis ms explored microstructural white matter alterations early ms clinically isolated syndrome cis comparing patients without cimethods based preceding tractbased spatial statistics analysis 3 tesla mri contrasted 106 patients early ms cis 49 healthy controls diffusion metrics fractional anisotropy fa mean diffusivity md extracted significant clusters using atlasbased approach fa md compared patients ci_p n 14 without cp_p n 81 cognitive impairment subset patients underwent ci screeningresults fa reduced ci_p compared cp_p splenium corpus callosum p 0001 right parahippocampal cingulum p 0002 fornix cres stria terminalis 0042 left posterior corona radiata p 0012 bilateral cerebral peduncles medial lemniscus cerebellar tracts increased md detected splenium corpus callosum p 001 cirelated localizations overlapped partially ms lesionsconclusion microstructural white matter alterations disease onset detectable ci_p compared cp_p known cognitively relevant fiber tracts indicating relevance early treatment initiation ms cispmid33787958 doi101007 s00062021010108,0.0
complement activation prominent feature mogad ann neurol 2021 sep 27 doi 101002 ana26226 online ahead printabstractmyelin oligodendrocyte glycoprotein mog antibody ab associated diseases mogad account substantial proportion pediatric adult patients present acquired demyelinating disorders pathogenesis optimal therapy incompletely understood profiled systemic complement activation adult pediatric patients mogad compared patients relapseonset multiple sclerosis patients neuromyelitis optica spectrum disorder pediatric control adult healthy donors proteins indicative systemic classical alternative complement activation substantially increased patients mogad compared control groups elevated levels detected adult pediatric cases across clinical syndromes complement inhibition explored therapeutic merit patients mogad article protected copyright rights reservedpmid34569094 doi101002 ana26226,1.0
machine learning classifier identify clinical radiological features relevant disability progression multiple sclerosis j neurol 2021 may 10 doi 101007 s00415021106057 online ahead printabstractobjectives evaluate accuracy datadriven approach machine learning classification predicting disability progression msmethods analyzed structural brain images 163 subjects diagnosed ms acquired two different sites participants followed 26 years disability progression defined according expanded disability status scale edss increment followup t2weighted lesion load t2ll thalamic cerebellar gray matter gm volumes fractional anisotropy normal appearing white matter calculated baseline included supervised machine learning classifiers age sex phenotype edss baseline therapy time followup period also included classes labeled stable progressed disability participants randomly chosen sites build sample including 50 patients showing disability progression 50 patients stable onethousand machine learning classifiers applied resulting sample testing overfitting classifier confusion matrix relative metrics feature importance evaluatedresults followup 36 participants showed disability progression classifier highest resulting metrics accuracy 079 area true positive versus false positive rates curve 081 sensitivity 090 specificity 071 t2ll thalamic volume disability baseline administered therapy identified important features predicting disability progression classifiers built radiological features higher accuracy built clinical featuresconclusions disability progression ms may predicted via machine learning classifiers mostly evaluating neuroradiological featurespmid33970338 doi101007 s00415021106057,0.0
objectivelyassessed physical activity selfreported activity pacing adults multiple sclerosis pilot study clin rehabil 2021 jun 162692155211024135 doi 101177 02692155211024135 online ahead printabstractobjective examine association selfreported activity pacing strategy manage fatigue symptoms objectivelymeasured physical activity behaviours adults multiple sclerosisdesign single crosssectional studysetting multiple sclerosis rehabilitation centre colchester united kingdomsubjects twentyone adults 59 9 years multiple sclerosismain measures physical activity behaviours activity level activity counts per minute activity variability highest activity counts per minute day divided activity counts per minute day measured accelerometers selfreported activity pacing activity pacing risk overactivity questionnaire fatigue severity fatigue severity scale healthrelated quality life rand12item shortform health survey measured scatter plots used explore associations measuresresults activity level 258 133 counts per minutes activity variability 4 1 selfreported activity pacing 3 1 fatigue severity 5 2 healthrelated quality life 43 8 increased selfreported activity pacing associated lower activity levels less variability daily activitiesconclusion investigation suggests people multiple sclerosis low physical activity levels inappropriately using activity pacing reactionary response multiple sclerosis symptomspmid34132109 doi101177 02692155211024135,0.0
cognitive impairment multiple sclerosis diagnosis monitoring neurol sci 2021 apr 1 doi 101007 s10072021051657 online ahead printabstractintroduction cognitive impairment ci prevalence 4570 people multiple sclerosis ms producing negative impact quality life personal life work early detection ci become important aspect considered adequate followup optimize social adaptation implement specific cognitive rehabilitation strategies aim work propose suitable cognitive evaluation patients ms based available efficient tools diagnosis monitoring purposes well supported literature review clinical experiencemethods multidisciplinary panel professionals field neurology neuropsychology neuroimaging performed literature review topic cognitive impairment assessment combined completed clinical experience produce set recommendationsresults limitations cognitive evaluation described shortage time resources neurology consultation scarceness absence specialized professionals availability importance tests adaptation doubts use define therapeutic efficiency recommend baseline annual screening evaluation suggest baseline periodic neuropsychological assessment latter change recommendation presence either positive screening test subjective cognitive complaints screeningtest results patient family report mismatch specific social work situationsconclusions cognitive evaluation performed patients diagnosed ms throughout followup necessary support creation multidisciplinary ms teams optimize evaluation followup ms patientspmid33796947 doi101007 s10072021051657,0.0
dysregulation long noncoding rna meg3 nlrc5 expressions patients relapsingremitting multiple sclerosis correlation genes immun 2021 nov 15 doi 101038 s41435021001544 online ahead printabstractlong noncoding rna meg3 nlrc5 genes involved immune system regulation nlrc5 meg3 documented rheumatoid arthritis therefore intended evaluate association expressions meg3 nlrc5 multiple sclerosis ms forty relapsing remitting ms rrms patients 20 group twenty healthy individuals enrolled expression level meg3 nlrc5 assessed peripheral blood mononuclear cells subgroup analysis demonstrated expression level meg3 reduced relapse patient group compared remission healthy groups p 0001 expression level nlrc5 higher whole patients compared healthy controls p 005 moreover negative correlation observed expression two genes r 073 p 00001 conclude findings showed dysregulation meg3 nlrc5 expressions rrms patients also converse association meg3 nlrc5 reflects role meg3 ms development probably mediated modulation nlrc5pmid34782775 doi101038 s41435021001544,0.0
humoral sarscov2 igg decay within 6 months covid19 healthy vaccinees need booster vaccine dose eur j intern med 2021 oct 27s09536205 21 003629 doi 101016 jejim202110027 online ahead printno abstractpmid34742628 doi101016 jejim202110027,0.0
homebased pilates symptoms anxiety depression fatigue among persons multiple sclerosis 8week randomized controlled trial mult scler 2021 apr 1913524585211009216 doi 101177 13524585211009216 online ahead printabstractbackground symptoms anxiety depression fatigue common comorbidities among persons multiple sclerosis pwms previous pilot study supported pilates feasible exercise modality may improve outcomes among pwmsobjective quantify effects 8 weeks homebased pilates symptoms anxiety depression fatigue among pwmsmethods total 80 pwms 69 female randomized twiceweekly homebased pilates guided dvd waitlist control validated questionnaires assessed anxiety depressive fatigue symptoms baseline weeks 2 4 6 8 using intention treat repeated measures analysis covariance rmancova adjusted baseline physical activity examined betweengroup differences across time hedges d quantified magnitude differences outcome change sensitivity analyses examined femaleonly samplesresults group time interactions statistically significant outcomes p 0005 pilates significantly reduced p 003 depressive symptoms quick inventory depressive symptomatology d 070 hospital anxiety depression scaledepression d 074 anxiety statetrait anxiety inventory d 030 hospital anxiety depression scaleanxiety d 049 cognitive d 044 physical d 078 psychosocial d 056 total fatigue d 076 femaleonly results materially sameconclusion homebased pilates significantly improved anxiety depressive fatigue symptoms among pwms minimaltomild mobility disability including moderatetolarge clinically meaningful improvements depressive fatigue symptomstrial registration clinicaltrialsgov nct04120207 pmid33870785 doi101177 13524585211009216,0.0
deubiquitylating enzymes potential target autoimmune diseases inflammopharmacology 2021 nov 18 doi 101007 s1078702100890z online ahead printabstractthe ubiquitinproteasome pathway responsible turnover different cellular proteins transport proteins presentation antigens immune system control cell cycle activities promote cancer enzymes remove ubiquitin deubiquitylating enzymes dubs play critical role central peripheral immune tolerance prevent development autoimmune diseases thus present potential therapeutic target treatment autoimmune diseases dubs function removing ubiquitin s target protein block ubiquitin chain elongation addition removal ubiquitin molecules significant impact immune responses dubs e3 ligases specifically cleave target protein modulate protein activity expression balance ubiquitylation deubiquitylation modulates protein levels also protein interactions dysregulation ubiquitinproteasome pathway results development various autoimmune diseases inflammatory bowel diseases ibd psoriasis multiple sclerosis ms systemic lupus erythematosus sle rheumatoid arthritis ra review summarizes current understanding ubiquitination autoimmune diseases focuses various dubs responsible progression autoimmune diseasespmid34792672 doi101007 s1078702100890z,0.0
low sun exposure acts synergistically high ebna1 antibody levels ms etiology eur j neurol 2021 aug 26 doi 101111 ene15082 online ahead printabstractbackground among multiple sclerosis ms patients association observed low levels vitamin d high epsteinbarr nuclear antigen 1 ebna1 antibody levels however whether sun exposure vitamin d moderates role epsteinbarr virus infection ms etiology unclear aimed investigate potential synergistic effects low sun exposure elevated ebna1 antibody levels regarding ms riskmethods used populationbased casecontrol study involving 2017 incident cases ms 2443 matched controls used logistic regression models calculate odds ratios ms 95 confidence intervals ci subjects different sun exposure habits ebna1 status potential interaction additive scale evaluated calculating attributable proportion due interaction ap results low sun exposure acted synergistically high ebna1 antibody levels ap 02 95 ci 00303 association increased ms risk interaction present regardless hladrb11501 statusconclusions low sun exposure may either directly indirectly affecting vitamin d levels synergistically reinforce pathogenic mechanisms aspects adaptive immune response related ms risk conveyed ebv infectionpmid34435414 doi101111 ene15082,0.0
mycosis fungoides patients multiple sclerosis report two cases ann dermatol venereol 2021 jun 28s01519638 21 00065x doi 101016 jannder202106002 online ahead printno abstractpmid34210534 doi101016 jannder202106002,0.0
bilateral breast necrotizing leukocytoclastic vasculitis first case report breast j 2021 nov 28 doi 101111 tbj14300 online ahead printabstractleukocytoclastic vasculitis lcv rare immune complexmediated condition affecting small vessels walls present case 48yearold woman necrotizing bilateral breast lcv treatment glatiramer acetate multiple sclerosis bilateral mastectomies debridement anterior abdominal wall required due rapidly evolving necrotizing process rapid assessment multidisciplinary approach fundamental treating rare lifethreatening conditionpmid34839564 doi101111 tbj14300,0.0
prevalence sexual dysfunction related risk factors men multiple sclerosis iran multicenter study neurol ther 2021 may 18 doi 101007 s40120021002570 online ahead printabstractintroduction sexual dysfunction sd common complaint patients multiple sclerosis ms aim study assess prevalence sd related risk factors men ms iranmethods crosssectional study 320 men diagnosed ms according mcdonald revised criteria recruited january june 2019 north south east west central parts iran patients assessed using male sexual health questionnaire mshq international index erectile function iief multiple sclerosis intimacy sexuality questionnaire msisq 19 sexual quality lifemen sqolm standard general health questionnaire ghq results sexual dysfunction defined total iief score 45 present 114 patients 356 results univariate logistic regression showed significant direct relations age 1050 95 ci 102108 expanded disability status scale edss 145 95 ci 12417 duration ms 1005 95 ci 10021009 msisq19 1103 95 ci 10781128 ghq 104 95 ci 103106 sqolm 0930 95 ci 09140947 smoking 1941 95 ci 11813188 nonms chronic disease 191 95 ci 120304 main sexual partner 256 95 ci 132494 significant inverse relations exercise 0584 95 ci 03640936 regular sexual activity 0241 95 ci 015040 prevalence sd results multiple logistic regression indicated age msisq19 sqolm independent predictive factors sd patientsconclusion prevalence sd men ms iran relatively high patients screened diagnosed treated sd influencing factorspmid34008168 doi101007 s40120021002570,0.0
detection multiple sclerosis lesions cervical cord magnims #39 mandatory#39 nongadolinium enhanced sagittal sequences optimal 3t neuroradiol j 2021 may 2019714009211017787 doi 101177 19714009211017787 online ahead printabstractbackground purpose magnetic resonance imaging multiple sclerosis consensus guidelines currently mandate three sagittal noncontrast enhanced sequences t2weighted fast spin echo proton densityweighted fast spin echo short tau inversion recovery however particular three sequences previously compared 3t study compared t2weighted fast spin echo proton densityweighted fast spin echo short tau inversion recovery well double inversion recovery sequence sagittal detection multiple sclerosis lesions cervical spinal cord 3tmethods nineteen multiple sclerosis patients underwent magnetic resonance imaging 3t sagittal t2weighted fast spin echo proton densityweighted fast spin echo short tau inversion recovery double inversion recovery november 2012 april 2013 two neuroradiologists independently reviewed images number lesions detected sequence recorded lesion conspicuity quantitatively assessed lesiontocordcontrast ratio lesion contrasttonoise ratio wilcoxon signed rank test performed statistical analysisresults proton densityweighted fast spin echo short tau inversion recovery detected 32 lesions compared t2weighted fast spin echo 37 lesions compared double inversion recovery lesiontocordcontrast ratio highest short tau inversion recovery lesion contrasttonoise ratio highest proton densityweighted fast spin echoconclusions study provides necessary evidentiary support 3t magnetic resonance imaging multiple sclerosis spinal magnetic resonance imaging protocol consensus guidelines 3t sagittal proton densityweighted fast spin echo short tau inversion recovery sequences allowed improved detection cervical spinal cord multiple sclerosis lesions compared t2weighted fast spin echo threedimensional double inversion recovery magnetic resonance imaging utilising t2weighted fast spin echo alone 3t insufficient lesion detectionpmid34014786 doi101177 19714009211017787,0.0
multiple sclerosis associated higher comorbidity healthcare resource use populationbased casecontrol study western mediterranean region eur j neurol 2021 jul 22 doi 101111 ene15030 online ahead printabstractbackground comorbidities common multiple sclerosis ms associated worse outcomes increased healthcare resource usage studied frequency comorbidities adverse health behaviors ahb ms patients mediterranean region cataloniamethods populationbased casecontrol study using primary healthcare information covering 80 catalonias population cases matched age sex randomlychosen controls ratio 15 demographic information comorbidities ahb annual visits sick leave days medication dispensing studied association comorbidities ms profile comorbidities according sex within ms cases assessed multivariate logistic regression models adjusting confounding variables healthcare resource usage analyzed ms cases compared controls within ms cases compared without comorbiditiesresults 5 548 ms cases 27 710 controls 70 female mean age 483 years included stroke 154 95ci 117199 epilepsy 246 95ci 194310 bipolar disorder 167 95ci 117236 depression 183 95ci 170198 frequent ms cases prone smoking less alcohol intaje among cases psychiatric comorbidities frequent women whereas cardiovascular diseases ahb frequent men ms patients particularly comorbidities higher healthcare resource usage controlsconclusions psychiatric comorbidities stroke epilepsy ahb common ms patients general population western mediterranean region catalonia presence comorbidities increases healthcare resource usage ms patientspmid34293826 doi101111 ene15030,0.0
experiences healthcare people living multiple sclerosis healthcare professionals health expect 2021 sep 4 doi 101111 hex13348 online ahead printabstractbackground multiple sclerosis ms chronic inflammatory neurodegenerative condition central nervous system commonly strikes young adulthood cure many people living ms pwms will significant contact range healthcare professionals hcps achieve optimal health outcomes ms important understand factors contribute positive negative healthcare experiences previous studies shown pwms want clear communication indepth relationships hcps however many studies lacked qualitative feedback hcpsobjective study aimed investigate healthcare experiences pwms hcps identify areas working well areas improvedmethods semistructured interviews 15 pwms 11 hcps seven neurologists four ms nurses across australia conducted interviews transcribed verbatim analysed thematicallyresults pwms hcps valued clear communication recognized uncertainties associated ms highlighted importance rapport pwms focused decisionmaking understanding roles expectations selfdirected management needs support hcps discussed issues related medical management providing hope reassurance barriers healthcare multidisciplinary careconclusion greater transparency communication particularly around approach care roles played hcps likely enhance healthcare experiences contribute better health outcomes pwmspublic contribution pwms hcps volunteered interviewed pwms assisted development interview content structurepmid34480516 doi101111 hex13348,0.0
systemwide mislocalization rnabinding proteins motor neurons new feature als neurobiol dis 2021 oct 8105531 doi 101016 jnbd2021105531 online ahead printabstractamyotrophic lateral sclerosis als motor neuron disease characterized progressive degeneration motor neurons mislocalization tar dnabinding protein 43 tdp43 early event formation cytoplasmic tdp43positive inclusions motor neurons hallmark als however underlying mechanism pathogenic impact mislocalization relatively unexplored previously reported abnormal ampk activation mediates tdp43 mislocalization motor neurons humans mice als present study hypothesized nuclear proteins mislocalized cytoplasm motor neurons due ampkmediated phosphorylation importin1 subsequently contribute neuronal degeneration als test hypothesis analyzed motor neurons sporadic als patients found ampk activated importin1 abnormally located nucleus multiple integrative molecular cellular approaches including proteomics immunoprecipitation western blot analysis immunohistological evaluations gradient analysis preribosomal complexes employed demonstrate numerous rna binding proteins mislocalized rodent motor neuron cell line nsc34 human motor neurons derived ipscs ampk activation used comparative proteomic analysis importin1 complexes immunoprecipitated phosphorylationdeficient mutant importin1 importin1s105a phosphomimetic mutant importin1 importin1s105d identify 194 proteins stronger affinity unphosphorylated form phosphorylated form importin1 furthermore go string analyses suggested rna processing protein translation major machinery affected abnormalities ampkimportin1 axis consistently expression importin1s105d alters assembly preribosomal complexes increases cell apoptosis collectively propose impairing importin1mediated nuclear import abnormal ampk activation motor neurons alters cellular distribution many rnabinding proteins pathogenically affect multiple cellular machineries motor neurons contribute als pathogenesispmid34634461 doi101016 jnbd2021105531,0.0
rna sequencing cd4 + t cells relapsingremitting multiple sclerosis patients relapse deciphering involvement novel genes pathways j mol neurosci 2021 jul 21 doi 101007 s12031021018788 online ahead printabstractcd4+ t cells known noteworthy potential modulator inflammation multiple sclerosis ms current study investigated transcriptome profile cd4+ t cells patients relapsingremitting ms rrms relapse phase performed rna sequencing cd4+ t cells isolated four relapsingremitting ms rrms patients relapse phase four age sexmatched healthy controls edger statistical method employed determine differentially expressed genes degs gene set enrichment analysis subsequently performed applying physical interaction network genes higher degrees selected hub genes total 1278 1034 genes defined significantly higher lower levels respectively cd4+ t cells rrms patients relapse phase compared healthy controls top downregulated genes jaml kdm3a detected degs remarkable chromosomes 1 2 respectively degs mainly enriched pathways regulation transcription dnatemplated regulation b cell receptor signaling pathway protein phosphorylation epidermal growth factor receptor signaling pathway positive regulation neurogenesis moreover 16 kegg pathways mostly associated immune system viral infections enriched constructed physical interaction networks uba52 tp53 shown highly ranked hub genes among upregulated downregulated genes respectively applying global transcriptome profiling cd4+ t cells deciphered involvement several novel genes pathways ms pathogenesis present results must confirmed vivo vitro studiespmid34286457 doi101007 s12031021018788,0.0
repository corticotropin injection improves quality metrics observational study multiple sclerosis relapse neurodegener dis manag 2021 dec 3 doi 102217 nmt20210030 online ahead printabstractaim determine whether clinicians evaluate american academy neurology aan quality metrics patients multiple sclerosis ms relapse whether repository corticotropin injection rci improves clinical patientreported outcomes associated metrics 2 6 months treatment methods multicenter prospective observational registry evaluating patients receiving rci ms relapse n 125 categorized data according aan quality metrics involving diagnosis disability fatigue cognitive impairment depression quality life results clinicians assessed 11 aan quality metrics patients ms relapse disability fatigue cognitive impairment depression quality life outcomes improved rci therapy conclusion rci associated improved quality metrics aan guidelines followed routine rci treatment ms relapsepmid34860120 doi102217 nmt20210030,0.0
targeting sialylation treat central nervous system diseases trends pharmacol sci 2021 oct 1s01656147 21 001711 doi 101016 jtips202109002 online ahead printabstractsialic acidbinding immunoglobulintype lectins siglecs membrane receptors preferentially expressed immune cells recognize sialylated proteins lipids rna sialic acids signaling siglecs increasingly recognized essential roles immune system homeostasis well nervous system development plasticity repair dysregulated sialylation siglec dysfunctions contribute several chronic diseases central nervous system cns current therapeutic options limited therapies targeting siglecs currently tested clinical trials area emerged one dynamic active fields glycobiology drug development review highlights recent insights sialic acid siglec function cns pathologies illustrates opportunities challenges development sialic acidbased siglectargeted therapies neurological diseasespmid34607695 doi101016 jtips202109002,0.0
providing personcentered care via telemedicine era covid19 multiple sclerosis j patient exp 2021 jan 12 82374373520981474 doi 101177 2374373520981474 ecollection 2021abstractthe coronavirus disease 2019 covid19 pandemic catalyzed rapid adoption telemedicine encompasses synchronous asynchronous interactions patients providers order facilitate rapid deployment numerous regulatory changes ensure caregivers can effectively communicate patients time illustrate model people processes technology work together address comprehensive needs multiple sclerosis ms patients provide template multidisciplinary academic practices can implement rapid shift virtual management pandemic using existing infrastructure can widely adopted care patients chronic diseases telemedicine incorporated entire practice encompasses neurology rehabilitation advanced practice providers fellows social work behavioral medicine patient satisfaction results remained stable across almost domains compared survey results typical inoffice visits experience demonstrates telemedicines transformative potential successfully managing multidisciplinary ms clinic time pandemic outlines potential path practices followpmid34179353 pmcpmc8205372 doi101177 2374373520981474,0.0
disability progression multiple sclerosis associated plasma neuroactive steroid profile neurol sci 2021 apr 8 doi 101007 s10072021052034 online ahead printabstractbackground neuroactive steroids nass exert multiple biological effects development inflammation effects nass disease progression multiple sclerosis ms uncertain prompting analyses nas profiles transition clinically isolated syndrome cis relapsingremitting rr msmethods subjects cis rrms healthy controls hcs recruited demographic clinical data well disability scores measured expanded disability status scale edss recorded matched plasma nas amino acid aa concentrations measuredresults hc n 17 cis n 31 rrms n 33 groups showed similar ages sex distribution although disability scores higher rrms group conversion rate cis rrms group 516 n 16 mean followup period 185 years rrms group showed significantly higher mean allopregnanolone aspartate taurine concentrations lower epiallopregnanolone concentrations cis patients higher lserineophosphate lower alanine arginine glutamine concentrations hc group among cis rrms groups multivariate hierarchical regressions revealed higher concentrations plasma tetrahydrodeoxycorticosterone thdoc may predict disability worseningconclusions rrms cis patients exhibited differing concentrations nass aas plasma thdoc pregnanolone might serve biomarkers disability worseningpmid33829329 doi101007 s10072021052034,0.0
microbiome methods experimental autoimmune encephalomyelitis curr protoc 2021 dec 1 12 e314 doi 101002 cpz1314abstractmicrobiome composition studies increasingly shedding light animal models disease paper describes protocol analyzing gut microbiome composition prior induction mice experimental autoimmune encephalomyelitis eae principal animal model human neuroinflammatory demyelinating disease multiple sclerosis ms also address provide data assessing impact mice reared different animal facilities eae induction furthermore discuss potential regulators gutmicrobiomebrain axis gmba relation neuroinflammation implications demyelinating disease states results suggest mice reared different animal facilities produce different levels eae induction results highlight importance accounting consistent environmental conditions inducing eae animal models disease 2021 wiley periodicals llc basic protocol 1 study composition gut microbiome neuroinflammatory model experimental autoimmune encephalomyelitis basic protocol 2 experimental procedures dna extraction microbiome analysispmid34870901 doi101002 cpz1314,1.0
confirmed 6month disability improvement worsening correlate longterm disability outcomes alemtuzumabtreated patients multiple sclerosis post hoc analysis carems studies neurol ther 2021 jun 24 doi 101007 s40120021002623 online ahead printabstractintroduction 2year carems trials nct00530348 nct00548405 patients relapsingremitting multiple sclerosis alemtuzumab showed superior efficacy versus subcutaneous interferon beta1a efficacy maintained two consecutive extensions nct00930553 nct02255656 post hoc analysis compared disability outcomes 9 years among alemtuzumabtreated patients according whether experienced confirmed disability improvement cdi worsening cdw neither cdi cdwmethods carems patients randomized receive two alemtuzumab courses 12 mg day 5 days baseline 3 days 12 months additional asneeded 3day courses extensions cdi cdw defined 10point decrease increase respectively expanded disability status scale edss score core study baseline confirmed 6 months assessed patients baseline edss score 20 improved stable edss scores defined 1point decrease 05point change either direction respectively core study baseline functional systems fs scores also assessedresults 511 eligible patients 43 experienced cdi 34 experienced cdw time year 9 patients experiencing cdi cdw counted individual group 29 experienced neither cdi cdw year 9 patients cdi 058point mean edss score change baseline 88 stable improved edss scores improvements occurred across fs primarily sensory pyramidal cerebellar domains patients cdw +171point mean edss score change 16 stable improved edss scores patients neither cdi cdw 010point mean edss score change 98 stable improved edss scoresconclusion cdi achievement point carems studies associated improved disability year 9 highlighting potential alemtuzumab change multiple sclerosis course conversely cdw point associated worsened disability year 9pmid34165694 doi101007 s40120021002623,0.0
brain imaging illuminates cognitive impairment multiple sclerosis nat rev neurol 2021 nov 4 doi 101038 s41582021005848 online ahead printno abstractpmid34737394 doi101038 s41582021005848,0.0
multiple sclerosis daily care rev infirm 2021 dec 70 276 3840 doi 101016 jrevinf202110012 epub 2021 oct 8abstractmultiple sclerosis progressive disease often associated image wheelchair however image reflect reality patients even basic treatment relapses can persist less visible fluctuating often misunderstood symptoms can source negative judgements chronic fatigue labelled laziness lack willpower balance problems interpreted drunkenness mood fluctuations likened hysteria etc consequences disease therefore physical psychological socioeconomic aim preserve quality daily life number aids treatments availablepmid34893176 doi101016 jrevinf202110012,0.0
magnetic resonance neurography management trigeminal neuralgia cohort study 55 patients oral surg oral med oral pathol oral radiol 2021 mar 11s22124403 21 001322 doi 101016 joooo202103003 online ahead printabstractobjective explore usefulness magnetic resonance neurography mrn diagnosis management trigeminal neuralgia tn study design total 55 patients clinically diagnosed tn imaged 30t magnetic resonance imaging images reconstructed show full course trigeminal nerve clinical findings included mean duration symptoms 4199 months mean visual analog scale pain intensity 598 final diagnoses microvascular compression 19 inflammation 21 microvascular compression inflammation 5 normal 5 tumor 1 peripheral nerve injury 2 multiple sclerosis 2 results mrn substantial impact diagnosis treatment 564 cases total 33 patients underwent intervention pain mrn substantial impact 545 treated patients correlation mrn results intervention response excellent 19 patients 576 moderate 14 424 pain reduced surgery interventional procedure cases 758 conclusions mrn suitable diagnosis clinical tn beneficial impact diagnosis clinical management moderatetoexcellent correlation intervention response diagnosis tn focus microvascular compression also conditions peripheral branches trigeminal nervepmid33934956 doi101016 joooo202103003,0.0
impact diseasemodifying treatments humoral response covid19 vaccination mirror response sarscov2 infection rev neurol paris 2021 jun 16s00353787 21 005695 doi 101016 jneurol202105001 online ahead printabstractobjective analyze humoral response covid19 vaccination patients multiple sclerosis ms according diseasemodifying treatments dmts comparison humoral response sarscov2 infectionmethods included 28 ms patients serological results covid19 vaccination pfizerbiontech moderna arnm 61 ms patients serological results covid19 covid19 group among patients followed ms center strasbourg france january april 2021 primary endpoint igg index according dmts anticd20 mab sphingosine 1phosphate receptor s1pr modulator treatments covid19 vaccine covid19 groupsresults vaccinated ms patients median igg index lower patients treated anticd20 mab patients treated s1pr modulator compared patients receiving dmts 480 158286 165 163485 1116 4341747 1272 6581886 respectively p0001 similar results found ms patients covid19conclusions patients ms treated s1pr modulators anticd20 mab reduced humoral response covid19 vaccinepmid34172292 doi101016 jneurol202105001,0.0
disability improvement clinically relevant outcome clinical trials relapsing forms multiple sclerosis mult scler 2021 mar 2613524585211000280 doi 101177 13524585211000280 online ahead printabstractbackground diseasemodifying therapies dmts can reduce risk disability worsening patients relapsing forms multiple sclerosis rms highefficacy dmts can lead confirmed sustained disability improvement cdi sdi objective methods post hoc analyses data transforms freedoms freedoms ii trials extensions assessed effects fingolimod 05125 mg day stabilizing improving disability 8 years participants rms cdi sdi rates compared participants initially randomized fingolimod interferon ifn1a placeboresults 8 years followup transforms 351 95 confidence interval ci 282431 assessed participants ifn1afingolimod switch group 419 366476 continuous fingolimod experienced cdi disability worsen approximately 70 similar results seen combined freedoms population proportionally fewer transforms participants achieved sdi ifn1afingolimod switch group continuous fingolimod 54 3095 vs 142 108184 p 001 conclusion cdi sdi outcomes interest clinical trials longterm followup participants rms monitoring cdi sdi addition disability worsening may facilitate understanding therapeutic benefit rms treatmentspmid33769117 doi101177 13524585211000280,0.0
expert perspectives covid19 vaccination people living multiple sclerosis neurol ther 2021 aug 4 doi 101007 s4012002100266z online ahead printno abstractpmid34347280 doi101007 s4012002100266z,0.0
male fertility relapsingremitting multiple sclerosis patients treated natalizumab ocrelizumab prospective casecontrol study mult scler 2021 apr 1913524585211009208 doi 101177 13524585211009208 online ahead printabstractscarce data available impact natalizumab ntz ocrelizumab ocr male fertility relapsingremitting multiple sclerosis rrms casecontrol prospective study gonadal steroids sperm parameters analysed time rrms diagnosis 12 months beginning investigated therapies sixteen men rrms sixteen matched healthy controls included enrolment 12 months therapy gonadal steroids sperm parameters men rrms differ healthy controls conclusion therapy ntz ocr impact fertility status cohort men rrms randomized prospective studies neededpmid33870777 doi101177 13524585211009208,0.0
multiple sclerosis risk worsening yellow fever vaccination mult scler 2021 apr 1913524585211006372 doi 101177 13524585211006372 online ahead printabstractbackground yellow fever vaccine yfv advised multiple sclerosis ms patients potential risk postvaccine relapsesobjective assess risk relapsingremitting multiple sclerosis rrms worsening yfvmethods noninterventional observational retrospective exposed nonexposed cohort study nested french national cohort including msresults 128 rrms included 1year annualized relapse rate arr following yfv differ exposed 0219 0420 nonexposed subjects 0208 0521 p 092 time first relapse different groups adjusted hazard ratio hr 133 95 confidence interval ci 053330 p 054 conclusion results suggest yfv worsen course rrmspmid33870792 doi101177 13524585211006372,0.0
t cells step sarscov2 vaccination b cell depletion nat rev neurol 2021 oct 2212 doi 101038 s4158202100582w online ahead printabstractdetailed immunological analysis new study provides insight mechanisms immune responses sarscov2 vaccination people receiving b celldepleting therapy multiple sclerosis findings implications clinical practice questions sarscov2 vaccination immunosuppression remainpmid34686837 pmcpmc8531891 doi101038 s4158202100582w,0.0
11 cpk11195 plasma metabolization rate multiple sclerosis patients healthy controls crosssectional study neural regen res 2021 dec 16 12 24942498 doi 104103 16735374313062abstract11cpk11195 positron emitter tracer used positron emission tomography pet imaging innate immune cell activation studies neuroinflammatory diseases image quantitative analysis necessary quantify intact fraction tracer arterial plasma imaging acquisition plasma intact fraction due complexity costs involved analysis important evaluate real necessity individual analysis 11cpk11195 pet imaging acquisition purpose study compare 11cpk11195 plasma metabolization rate healthy controls multiple sclerosis ms patients evaluate interference sex age treatment disease phenotype tracer intact fraction measured arterial plasma samples 11cpk11195 metabolization rate arterial plasma quantified high performance liquid chromatography samples ms patients n 50 healthy controls n 23 20 45 60 minutes 11cpk11195 injection analyses also stratified sex age treatment type ms phenotype results showed significant differences metabolization rate healthy controls ms patients stratified samples conclusion 11cpk11195 metabolization rate patients ms healthy controls affected sex age treatment disease phenotype thus findings contribute exempting necessity tracer metabolization determination 11cpk11195 pet imaging acquisition using population metabolization rate average study procedures approved ethics committee research projects analysis hospital das clinicas university sao paulo medical school approval 624065 april 23 2014pmid33907039 doi104103 16735374313062,0.0
assessing presence oligoclonal igm bands prognostic biomarker cognitive decline early stages multiple sclerosis brain behav 2021 nov 18e2405 doi 101002 brb32405 online ahead printabstractbackground association found presence lipidspecific oligoclonal igm bands lsocmb cerebrospinal fluid severe clinical multiple sclerosis courseobjective investigate lipidspecific oligoclonal igm bands prognostic biomarker cognitive impairment early stages multiple sclerosismethods fortyfour patients underwent neuropsychological assessment baseline 4 years cognitive performance followup compared adjusting age education anxietydepression baseline performanceresults lsocmb+ patients performed worse longterm storage selective reminding test p 018 conclusion remarkable cognitive differences lsocmb lsocmb+ patients early stages mspmid34796675 doi101002 brb32405,0.0
effect exercise fatigue multiple sclerosis patients network metaanalysis int j sports med 2021 aug 10 doi 101055 a15241935 online ahead printabstractfew studies directly compared effects different exercise therapies reducing fatigue patients multiple sclerosis thus conducted frequentist network metaanalysis analyze compare effectiveness different types exercise reducing multiple sclerosisrelated fatigue relevant randomized controlled trials searched pubmed web science cochrane library databases date inception april 1 2021 total 27 articles involving 1470 participants 10 types interventions met inclusion criteria results indicated aquatic exercise ranked effective among interventions aerobic exercise smalltomoderate effect sizes interventions shown better control group except climbing climbing intervention ranked worse controls findings merit investigation future clinical trialspmid34375988 doi101055 a15241935,0.0
toxoplasma gondii multiple sclerosis systematic review metaanalysis eur j neurol 2021 aug 9 doi 101111 ene15055 online ahead printabstractbackground according hygiene hypothesis infections agents parasites protective role risk developing multiple sclerosis ms among parasites toxoplasma gondii intracellular parasite showed evidence protective effectobjective summarize available evidence association toxoplasma gondii infection msmethods systematic review available articles published november 2020 conducted independently two investigators following databases pubmed scopus lissa scielo association t gondii infection ms pooled randomeffects modelresults 562 articles seven included systematic review metaanalysis global population 752 ms cases 1282 controls t gondii infection associated ms pooled odds ratio 068 95 confidence intervals 050 093 conclusion available evidence supports hypothesis t gondii infection represents protective factor towards development mspmid34374174 doi101111 ene15055,0.0
exploring reported genes microglia rnasequencing data uses considerations glia 2021 aug 18 doi 101002 glia24078 online ahead printabstractthe advent rnasequencing techniques made possible generate large unbiased gene expression datasets tissues cell types several studies describing gene expression data microglia alzheimers disease multiple sclerosis published aiming generate insight role microglia neurological diseases though raw sequencing data often deposited open access databases accessible source data scientists reported published manuscripts observed relatively limited overlap reported differentially expressed genes various microglia rnasequencing studies multiple sclerosis alzheimers diseases clear differences experimental set influenced number overlapping reported genes however even experimental set similar observed overlap reported genes low identified papers reporting large numbers differentially expressed microglial genes generally showed higher overlap papers addition though pathology present within tissue used sequencing can greatly influence microglia gene expression often pathology present samples used sequencing underreported leaving difficult assess data whereas reanalyzing every raw dataset reduce variation contributes observed limited overlap reported genes feasible labs without access bioinformatic expertise study thus provide overview data present manuscripts supplementary files data can interpretedpmid34409652 doi101002 glia24078,0.0
epsteinbarr virus current questions challenges tumour virus res 2021 may 27200218 doi 101016 jtvr2021200218 online ahead printabstractepsteinbarr virus ebv infects people worldwide persists life due complicated interplay lytic infection multiple types latent infections usually asymptomatic ebv causative agent several types cancer strong association multiple sclerosis exactly ebv promotes diseases rare consequences infection incompletely understood will discuss current ideas disease induction ebv including importance lytic protein expression context latent infection well possible importance specific ebv variants disease inductionpmid34052467 doi101016 jtvr2021200218,0.0
post covid19 vaccination neuromyelitis optica spectrum disorder case report amp amp mri findings radiol case rep 2021 dec 16 12 38643867 doi 101016 jradcr202109033 epub 2021 oct 13abstractthere rising concerns among medical community public regarding side effects different vaccines developed throughout world short longterm effects particularly covid19 vaccines notably postvaccination demyelinating diseases acute disseminated encephalomyelitis transverse myelitis multiple sclerosis relapses reported present case 32yearold male presented 2 weeks history acute confusional state imbalance 1 week receiving second dose covid19 vaccination mri findings showed typical distribution neuromyelitis optica spectrum disorder patient positive aqp4 igg pathogenesis behind developing neuromyelitis optica vaccines still unknown case reports reported postvaccination neuromyelitis optica spectrum disorder knowledge first case published neuromyelitis optica following exposure covid19 vaccinepmid34659602 pmcpmc8512112 doi101016 jradcr202109033,1.0
supporting adaptation announcement diagnosis multiple sclerosis 2#x2f 2 rev infirm 2021 nov 70 275 3739 doi 101016 jrevinf202108015 epub 2021 aug 27abstractthe emotional reactions arise diagnosis multiple sclerosis made repeated stage pathology confront person reality thought mastered fighting disease means continuing live ones personal family love professional life matter positive thinking becoming aware ones limits finding right balance ones desires ones capacities relationship trust developed various professionals will accompany patient throughout treatment essentialpmid34752360 doi101016 jrevinf202108015,0.0
epsilon 2 epsilon 3 epsilon 4 variants apoe rs2228570 vdr rs4588 rs7041 vdbp polymorphisms patients multiple sclerosis casecontrol study turkish population int j clin pract 2021 sep 6e14801 doi 101111 ijcp14801 online ahead printabstractaim study multiple sclerosis ms degenerative disease characterized autoimmune demyelination central nervous system yet underlined genetics environmental markers still controversial impact vitamin d cholesterol disease activity phrased many studies however data available turkish population limited aimed investigate effect vitamin drelated polymorphisms vdbp vdr cholesterolrelated variants apoe turkish ms patientsmaterials methods total dnas extracted peripheral blood samples fiftyone ms patients fifty healthy volunteers rs4588 rs7041 polymorphisms vdbp rs2228570 vdr well 2 3 4 variants apoe investigated rtpcr biochemical parameters thought associated ms also measured results evaluated statisticallyresults homozygous mutant genotype g allele rs2228570 vdr well heterozygous genotype rs4588 vdbp found statistically high patients total cholesterol triglyceride ldlc levels found significantly high whereas hdlc vitamin d levels low patients association found rs4588 variation high triglyceride levels similar correlations found 2 genotype low ldlc level 3 genotype higher ldlc gender triglyceride hdlc aa genotype rs4588 significant effect ms progressionconclusion variations rs2228570 rs4588 vitamin d deficiency biological parameters related cholesterol metabolism may associated ms riskpmid34486787 doi101111 ijcp14801,1.0
t cell composition polygenic multiple sclerosis risk populationbased study children eur j neurol 2021 jul 12 doi 101111 ene15019 online ahead printabstractbackground patients multiple sclerosis altered t cell function composition common genetic risk variants ms affect proteins function immune system currently unclear extent t cell composition affected genetic risk factors ms may precede possible disease onset aim assess whether ms polygenic risk score prs associated altered t cell composition large cohort children general populationmethods included genotyped participants populationbased generation r study immunophenotyping blood t cells performed age 6 years anova analyses used determine impact msprss total t cell numbers n1 261 cd4+ cd8+ lineages subsets therein n675 addition t cell specific prss constructed based functional pathway dataresults msprs negatively correlated cd8+ t cell frequencies p292103 resulted positive association cd4+ cd8+ t cell ratios p827109 associations mainly driven 2 195 genomewide significant ms risk variants main genetic risk variant ms hladrb11501 hlab risk variant observed significant associations t cell specific prssconclusion results suggest msassociated genetic variants affect t cell composition childhood general populationpmid34251726 doi101111 ene15019,0.0
design implementation instrumented data glove measures kinematics dynamics human hand annu int conf ieee eng med biol soc 2021 nov 202172297232 doi 101109 embc4616420219630204abstracthuman hands versatile biomechanical architectures can perform simple movements grasping complicated movements playing musical instrument extremely dependable useful parts human body can debilitated due movement disorders parkinsons disease stroke spinal cord injury multiple sclerosis cerebral palsy cases precisely measuring residual abnormal hand function becomes critical assessment help clinicians physical therapists diagnosis treatment prescribing appropriate prosthetics rehabilitation therapies current methodologies used measure abnormal residual hand function either paperbased scales prone human error expensive motion tracking systems cost complexity restrict usability methods clinical environments paper present lowcost instrumented glove can measure kinematics dynamics human hand leveraging recent advances 3d printing technologies flexible sensorspmid34892767 doi101109 embc4616420219630204,0.0
ectopic lymphoid follicles progressive multiple sclerosis patients animal models immunology 2021 jul 22 doi 101111 imm13395 online ahead printabstractectopic lymphoid follicles elfs resembling germinal centerlike structures emerge variety infectious autoimmune well neoplastic diseases elfs can found meninges around 40 investigated progressive multiple sclerosis ms postmortem brain tissues associated severity cortical degeneration clinical disease progression predominant importance progressive neuronal damage progressive ms phase appears meningeal inflammation comprising diffuse meningeal infiltrates b cell aggregates compartmentalized elfs however absence uniform definition elfs impedes reproducible comparable neuropathological research field review article will first highlight historical aspects milestones around discovery elfs meninges progressive ms patients next step discuss animal models may contribute understanding mechanisms underlying elf formation finally summarize challenges investigating elfs propose potential directions future researchpmid34293193 doi101111 imm13395,0.0
carnosine skeletal muscle dysfunction rodent multiple sclerosis model amino acids 2021 oct 12 doi 101007 s00726021030865 online ahead printabstractmuscle weakness fatigue primary manifestations multiple sclerosis ms chronic disease central nervous system interventions enhance muscle function may improve overall physical wellbeing ms patients recently described levels carnosine endogenous muscle dipeptide involved contractile function fatigueresistance reduced muscle tissue ms patients monophasic rodent ms model experimental autoimmune encephalomyelitis eae present study aimed 1 confirm finding chronic eae model along characterization structural functional muscle alterations 2 investigate effect carnosine supplementation increase restore muscle carnosine levels improve muscle function eae performed muscle immunohistochemistry ex vivo contractility measurements examine muscle structure function different stages eae following nutritional intervention oral carnosine 3 15 30 g l drinking water immunohistochemistry revealed progressively worsening muscle fiber atrophy switch towards fasttwitch muscle phenotype eae using ex vivo muscle contractility experiments observed reductions muscle strength contraction speed changes muscle fatigability eae mice however carnosine levels unaltered stages eae even though oral carnosine supplementation dosedependently increased muscle carnosine levels + 94 56 days eae improve muscle function eae mice conclusion eae mice display significant yet timedependent muscular alterations carnosine intervention improve muscle function eaepmid34642824 doi101007 s00726021030865,0.0
letter editor re effect pelvic floor exercise program incontinence sexual dysfunction multiple sclerosis patients altunan et al ijun 2021 531059 int urol nephrol 2021 jul 22 doi 101007 s11255021029589 online ahead printno abstractpmid34292491 doi101007 s11255021029589,0.0
outcome covid19 patients history taking rituximab narrative review iran j med sci 2021 nov 46 6 411419 doi 1030476 ijms2021887171946abstractcoronavirus disease 2019 covid19 recently emerging disease caused severe acute respiratory syndrome coronavirus 2 sarscov2 notably safety immunosuppressive medications major concern infectious disease pandemic rituximab rtx monoclonal antibody cd20 molecule widely used treatment various diseases mostly autoimmune diseases malignancies previous studies indicated rtx immunosuppressive medication may associated increased risk infections moreover given wide use rtx necessity determining different aspects rtx use covid19 era strongly felt reviewed current studies clinical courses patients sarscov2 infection appears use rtx increase morbidity mortality patients however underlying diseases concomitant medications may play role disease course concerns vaccine efficacy patients receiving rtx still need addressed therefore controlled studies needed better conclusionpmid34840381 pmcpmc8611224 doi1030476 ijms2021887171946,0.0
menstrual cycle resumption female fertility autologous hematopoietic stem cell transplantation multiple sclerosis mult scler 2021 mar 1213524585211000616 doi 101177 13524585211000616 online ahead printabstractdata fertility autologous hematopoietic stem cell transplantation ahsct women multiple sclerosis ms inconclusive study aims report postahsct menstrual resumption multicenter mswomen cohort 43 women 30 70 recovered menses mean time 68 months older age odds ratio 05 p 00001 previous pulsed cyclophosphamide 044 p 0005 independently associated reduced menstrual recovery probability conditioning regimens intensity resulted associated postprocedure amenorrhea results highlight younger age significantly associated menses recovery proper fertility counseling ms women candidated ahsct prior posttransplantation therefore warrantedpmid33709839 doi101177 13524585211000616,0.0
longterm outcome predictors longterm disease activity natalizumabtreated patients multiple sclerosis real life data austrian ms treatment registry j neurol 2021 apr 22 doi 101007 s0041502110559w online ahead printabstractobjectives evaluate longterm effectiveness natalizumab ntz determine demographic clinical radiological predictors regarding longterm disease activity 7 years nationwide observational cohort using data collected prospectively reallife settingmaterials methods analysed data 230 patients austrian multiple sclerosis treatment registry amstr started treatment ntz time since 2006 stayed ntz least 7 years without treatment gap three monthsresults estimated mean annualised relapse rates arr mean treatment period 93 years 007 ntz sustained edss progression 12 weeks observed 36 19 patients 24 weeks 31 163 cases sustained edss regression 12 24 weeks seen 45 237 42 221 cases baseline parameters 1 gadoliniumenhancing mri lesion s incidence rate ratio irr 0409 95 ci 02830593 p 0001 arr 1 prior 12 month treatment initiation ntz irr 0353 95 ci 02000623 p 0001 edss 1 incidence rate ratio irr 0081 95 ci 00110581 p 0012 significantly associated reduced relapse risk whereas disease duration 5 years increased significantly arr irr 1851 95 ci 12492743 p 0002 predictive baseline parameter experiencing edss progression sustained 12 24 weeks age 35 years hr 2482 95 ci 11105549 p 0027 hr 2492 95 ci 10395978 p 0041 respectively conclusions reallife data show stable disease course regarding relapse activity disease progression ntz treatment 7 years main predictors disease activity higher relapse rate treatment initiation higher disability shorter disease duration absence gadoliniumenhancing mri lesions baseline older age ntz start significant risk factor disease progression longtermpmid33890167 doi101007 s0041502110559w,0.0
multifactorial model multiple sclerosis gait changes across different disability levels ieee trans biomed eng 2021 feb 24 pp doi 101109 tbme20213061998 online ahead printabstractobjective mobility assessment critical clinical management people multiple sclerosis pwms instrumented gait analysis provides plethora metrics quantifying concurrent factors contributing gait deterioration however gait model discriminating underlying features contributing deterioration lacking pwms study aimed developing validating modelmethods gait 24 healthy controls 114 pwms mild moderate severe disability measured inertial sensors shanks lower trunk walking 6 minutes along hospital corridor twenty thirtysix initially explored metrics computed sensor data met quality criteria exploratory factor analysis analysis provided sought model underwent confirmatory factor analysis used characterize gait impairment across three disability groupsresults gait model consisting five domains rhythm variability pace asymmetry forward lateral dynamic balance revealed factor analysis able highlight gait abnormalities across disability groups significant alterations rhythm variability asymmetry pacebased features present mild group profound moderate severe groups deterioration dynamic balancebased features noted pwms moderate severe disabilityconclusion conceptual model gait diseasespecific mobility assessment pwms successfully developed testedsignificance new model built metrics represent gait impairment pwms highlighted clinically relevant changes across different disability levels including clinically observable walking disability shows clear potential monitoring biomarker pwmspmid33625975 doi101109 tbme20213061998,0.0
il35 critical regulator immunity helminth infections associated multiple sclerosis immunology 2021 jul 1 doi 101111 imm13389 online ahead printabstractmultiple sclerosis ms currently thought arise interactions genetic susceptibility environmental factors infections general trigger autoimmune responses causing clinical manifestations disease however result regulatory t treg regulatory b breg cell induction helminthinfections tend dampen disease activity il35 newest member il12 family inhibitory cytokine composed ebi3 chain subunit il12p35 subunit aim study investigate role il35 parasite infections occurring individuals ms numbers il35producing breg cells higher csf helminthinfected uninfected ms subjects finding associated decreased mri disease activity interestingly stimulation cd19+ b cells il35 promotes conversion cells breg cells producing il35 il10 coculture b cells helminthinfected ms patients inhibits proliferation th1 th17 myelinpeptide specific t cells well production ifn il17 following activation cd4+ cd25+ treg cells significantly upregulate expression ebi3 il12p35 mrna furthermore cd4+ cd25 t cells activated presence il35 induce population cells regulatory function known itr35 finally b cells normal individuals cultured vitro presence helminth antigen sea increase expression transcription batf irf4 irf8 acquiring pattern similar il35 breg cells data highlight important immunoregulatory effects il35 breg treg cells observed helminthinfected ms subjectspmid34197631 doi101111 imm13389,1.0
therapeutic potential target nlrp3 inflammasome multiple sclerosis pharmacol ther 2021 apr 23107880 doi 101016 jpharmthera2021107880 online ahead printabstractinflammasomes multiprotein macromolecular complexes typically comprise three units sensor adaptor procaspase1 assembly inflammasome dictated unique pattern recognition receptors prrs response pathogenassociated molecular patterns pamps endogenous dangerassociated molecular patterns damps cytosol host cells promote maturation secretion il1 il18 inflammatory process specific inflammasomes involved host defense response different pathogens latter evolved multiple corresponding mechanisms inhibit inflammasome activation nucleotidebinding oligomerization domain leucinerich repeat pyrin domaincontaining 3 nlrp3 inflammasome best understood terms molecular mechanisms promising therapeutic target immunerelated disorders multiple sclerosis ms autoimmune disease characterized inflammatory demyelination white matter central nervous system increased levels il1 cerebrospinal fluid csf relapsed patients deposition caspase1 spinal cord direct involvement nlrp3 inflammasome occurrence development ms ascertained experimental autoimmune encephalomyelitis eae animal model review focused mechanisms underlying activation nlrp3 inflammasome ms eae well inhibitors specifically target complex alleviate disease progression order unearth new therapeutic strategies mspmid33901504 doi101016 jpharmthera2021107880,1.0
longterm comparative analysis evidence disease activity neda3 status multiple sclerosis patients treated natalizumab fingolimod 4 years neurol sci 2021 mar 6 doi 101007 s1007202105127z online ahead printabstractbackground comparative effectiveness natalizumab fingolimod followup longer 2 years addressed yetobjectives compare effect evidence disease activity neda3 relapsingremitting multiple sclerosis rrms patients treated natalizumab fingolimod least 4 yearsmethods included rrms patients switched firstline agents natalizumab fingolimod patients propensity score ps matched 1to1 basis percentages patients reaching neda3 status 2 4 years followup compared using chisquare test risk achieving neda3 4 years explored matched samples cox regression modelsresults evaluated 174 psmatched patients patients receiving natalizumab reached neda3 status 2 4 years frequently exposed fingolimod 63 vs 44 p0037 457 vs 258 p0015 respectively patients receiving natalizumab significant lower risk achieving neda3 status 4 years compared exposed fingolimod hazard ratio 95 confidence interval 054 036080 p0002 conclusions although medications effective patients nonresponding firstline agents natalizumab seems superior fingolimod rrms obtaining neda3 status 4 yearspmid33677753 doi101007 s1007202105127z,0.0
myelin oligodendrocyte glycoprotein mog antibodymediated disease difficulty predicting relapses mult scler relat disord 2021 aug 28 56103229 doi 101016 jmsard2021103229 online ahead printabstractbackground many patients myelin oligodendrocyte glycoprotein antibodymediated disease mogad will monophasic course 3080 patients will relapse initial attack known factors predict relapse describe clinical experience mogad evaluate factors correlate relapsing diseasemethods retrospective multiinstitutional study 54 patients mogad including 17 children 37 adults mannwhitney u fischers exact tests used comparisons logistic regression correlationsresults incident attack phenotype included acute disseminated encephalomyelitis 15 unilateral optic neuritis 39 bilateral 24 transverse myelitis tm 11 tm 11 pediatric patients likely adults present adem p 009 less likely present unilateral p 04 31 patients 57 relapsing disease course time first relapse 82 months median annualized relapse rate 097 months 40 patients n 22 first relapse occurred following withdrawal treatment incident attack 5 patients converted seronegative follow 2 later relapsed logistic regression revealed significant relationship age gender race presentation phenotype antibody titer cerebrospinal fluid results risk relapse patients started disease modifying therapy dmt prior first relapse n 11 64 remained monophasic 50 n 15 patients dmt continued disease activity requiring treatment adjustmentconclusions difficult predict patients mogad will relapse research needed determine optimal timing choice treatmentpmid34479112 doi101016 jmsard2021103229,1.0
cns inflammation natalizumab therapy multiple sclerosis retrospective histopathological csf cohort study brain pathol 2021 may 6e12969 doi 101111 bpa12969 online ahead printabstractnatalizumab recombinant humanized monoclonal antibody directed 4 subunit integrins 41 47 approved treatment active relapsingremitting ms although natalizumab highly beneficial drug effectively reduces risk sustained disability progression rate clinical relapses patients respond higher risk developing progressive multifocal leukoencephalopathy pml histopathological effects natalizumab therapy still unknown therefore performed detailed histological characterization cns inflammatory cell infiltrate 24 brain specimens natalizumab treated patients consisting 20 biopsies 4 autopsies 21 ms controls complement analysis immune cells blood cerebrospinal fluid csf 30 natalizumabtreated patients 42 ms controls quantified flow cytometry inflammatory infiltrates within lesions mainly composed t cells macrophages b cells plasma cells dendritic cells significant difference numbers t cells macrophages microglial cells lesions natalizumabtreated patients compared controls shift towards cytotoxic t cells memory phenotype observed csf plasma cells significantly increased active demyelinating lesions natalizumabtreated patients correlation clinical disability observed dendritic cells within lesions found reduced longer ongoing therapy duration findings suggest natalizumab completely prevent immune cells entering cns associated accumulation plasma cells pathogenic clinical significance known b cells considered serve reservoir jc virus observed plasma cell accumulation reduction dendritic cells cns natalizumabtreated patients may potentially play role pml developmentpmid33955606 doi101111 bpa12969,1.0
plasma neurofilament light chain concentrations biomarker clinical radiologic outcomes relapsing multiple sclerosis post hoc analysis phase 3 ozanimod trials eur j neurol 2021 jul 22 doi 101111 ene15009 online ahead printabstractbackground investigated plasma neurofilament light chain concentrations pnfl biomarker neuroaxonal damage disease activity using data phase 3 trials ozanimod relapsing multiple sclerosis rms methods pnfl measured ozanimod 046 mg 092 mg daily interferon 1a 30 g weekly randomized doubleblind sunbeam radiance trials post hoc analyses investigated relationships pnfl baseline median percentage change baseline month 12 sunbeam 24 radiance clinical magnetic resonance imaging outcomesresults median q1 q3 baseline pnfl available 1244 1346 sunbeam participants 1470 1016 2326 pg ml 1109 1313 radiance participants 1335 942 2041 pg ml baseline gadoliniumenhancing gde t2 lesion counts increased brain volume decreased increasing baseline pnfl baseline pnfl higher versus without ontreatment relapse median percentage reduction pnfl 12 months sunbeam n1238 24 months radiance n1088 greater ozanimod 2027 interferon 1a 1316 p001 greater pnfl reduction associated fewer gde lesions fewer new enlarging t2 lesions per scan less loss brain volume lower annualized relapse rate arr evidence disease activity following models predicted arr 05111 + 00116 x nfl 12 months sunbeam 04079 + 00088 x nfl 24 months radiance conclusions pnfl associated clinical radiologic measures disease treatment effects rms supporting use biomarkerpmid34292643 doi101111 ene15009,0.0
mir1323p mir106b5p mir19b3p associated brainderived neurotrophic factor production clinical activity multiple sclerosis pilot study genet test mol biomarkers 2021 nov 25 11 720726 doi 101089 gtmb20210183abstractintroduction brainderived neurotrophic factor bdnf levels reduced advanced stages multiple sclerosis ms may associated reduced regenerative capability progressive ms brought increased attention factors regulating bdnf production ms aim investigate link neurotrophinregulating micrornas mirna disease progression ms materials methods serum levels bdnf peripheral blood mononuclear cell pbmc expression levels mir1323p mir106b5p mir19b3p respectively measured elisa real time pcr twelve relapsing remitting ms rrms patients seven secondary progressive ms spms patients fourteen healthy controls results serum bdnf levels significantly reduced spms patients selected mirnas significantly upregulated pbmc rrms spms patients mir106b5p mir19b3p respectively showed highest sensitivity specificity ms diagnosis receiver operating characteristic curve analysis negative correlation levels bdnf mirnas rrms likewise levels bdnf investigated mirnas showed positive negative correlations respectively expanded disability status scale rrms spms patients mir1323p mir106b5p levels showed positive correlations progression index spms patients conclusion results suggest increased disability associated downregulation mir1323p mir106b5p mir19b3p rrms patients putatively promotes increased production neuroprotective bdnf compensatory mechanism link investigated mirnas bdnf rrms appears hold spms might one factors contributing reduced regenerative ability progressive stage mspmid34788141 doi101089 gtmb20210183,1.0
validity italian multiple sclerosis neuropsychological screening questionnaire neurol sci 2021 mar 2 doi 101007 s10072021051411 online ahead printabstractthe multiple sclerosis neuropsychological questionnaire msnq brief questionnaire useful screening patients multiple sclerosis ms risk cognitive impairment includes patient selfassessment msnqp section caregiver informant msnqi studys aim validate italian version msnq compare msnq scores symbol digit modality test sdmt beck depression inventory bdi expanded disability status scale edss score measuring cognitive skills mood status physical disability respectively enrolled 122 ms patients related caregivers ms center tor vergata university hospital rome final study sample consisted 122 patients ms 90 relapsingremitting 24 secondary progressive 8 primary progressive results highlighted msnq unidimensional factor structure correlational analyses found good correlation versions msnqp msnqi questionnaire msnqp msnqi correlated clinical variables specifically cognitive impairment mood disorder disability italian version msnq reliable useful screening tool identify ms patients high risk cognitive impairmentpmid33651198 doi101007 s10072021051411,0.0
neuroimmune connections corticotropinreleasing hormone mast cells novel strategies treatment neurodegenerative diseases neural regen res 2021 nov 16 11 21842197 doi 104103 16735374310608abstractcorticotropinreleasing hormone critical component hypothalamicpituitaryadrenal axis plays major role bodys immune response stress mast cells sensors effectors interaction nervous immune systems first responders stress mast cells can initiate amplify prolong neuroimmune responses upon activation corticotropinreleasing hormone plays pivotal role triggering stress responses related diseases acting receptors mast cells corticotropinreleasing hormone can stimulate mast cell activation influence activation immune cells peripheral nerves modulate neuroimmune interactions latest evidence shows release corticotropinreleasing hormone induces degranulation mast cells stress conditions leading disruption bloodbrain barrier plays important role neurological diseases alzheimers disease parkinsons disease multiple sclerosis autism spectrum disorder amyotrophic lateral sclerosis recent studies suggest stress increases intestinal permeability disrupts bloodbrain barrier corticotropinreleasing hormonemediated activation mast cells providing new insight complex interplay brain gastrointestinal tract neuroimmune target mast cells site corticotropinreleasing hormone directly participates inflammatory responses nerve terminals review focus neuroimmune connections corticotropinreleasing hormone mast cells aim providing novel potential therapeutic targets inflammatory autoimmune nervous system diseasespmid33818491 doi104103 16735374310608,0.0
kappa free light chain index diagnostic biomarker multiple sclerosis realworld investigation j neurochem 2021 sep 3 doi 101111 jnc15500 online ahead printabstractkappa free light chain kflc index measure intrathecal production free kappa chains increasingly recognized diagnostic potential multiple sclerosis ms quantitative alternative igg oligoclonalbands ocbs objective investigate sensitivity specificity overall diagnostic accuracy kflcindex ms kflcindex prospectively determined part diagnostic workup patients suspected ms n327 may 2013 february 2020 patients clinically isolated syndrome cis radiologically isolated syndrome ris ms markedly higher kflcindex 446 iqr 16128 compared subjects neuroinflammatory disorders onid symptomatic controls sc 219 iqr 168298 p0001 kflcindex sensitivity 093 95 ci 088095 specificity 087 95 ci 08092 discriminate cis ris ms onid sc auc 094 95 ci 091097 p0001 kflcindex intrathecal fraction kflc similar accuracies detect ms treatment diseasemodifying therapy dmt influence level kflcindex affected demographic factors associated degenerative inflammatory biomarkers cerebrospinal fluid csf kflcindex ms diagnostics methodological advantages compared ocb independent subjective interpretation moreover attractive diagnostic tool since diagnostic specificity sensitivity kflcindex similar ocbs kflcif better iggindex show kflcindex influenced neither dmt demographic factors inflammatory degenerative processes ms determined biomarkers csfpmid34478561 doi101111 jnc15500,0.0
matrine treatment induced a2 astrocyte phenotype protected bloodbrain barrier cns autoimmunity j chem neuroanat 2021 jul 16102004 doi 101016 jjchemneu2021102004 online ahead printabstracttype 1 astrocytes a1 highly proinflammatory neurotoxic prevalent multiple sclerosis ms addition ms animal model experimental autoimmune encephalomyelitis eae immune cells must cross bloodbrain barrier bbb infiltrate parenchyma central nervous system cns order induce neurological deficits previously reported treatment eae matrine mat quinazine alkaloid derived sophorae flavescens effectively inhibited cns inflammation promoted neuroregeneration however impact mat treatment astrocyte phenotype known present study showed mat treatment inhibited generation neurotoxic a1 astrocytes promoted neuroprotective a2 astrocytes cns eae likely inhibiting production a1inducing cytokine cocktail mat also downregulated expression vascular endothelial growth factora vegfa upregulated tight junction proteins claudin 5 occludin thus protecting bbb cns inflammationinduced damage moreover mat treatment promotes formation astrocyte tight junctions glia limitans thereby limiting parenchymal invasion cns immune cells taken together inhibition a1 astrogliogenesis dual effects bbb astrocytic glia limitans may mechanisms whereby mat significantly improves eae clinical scores neuroprotectionpmid34280490 doi101016 jjchemneu2021102004,1.0
safety bnt162b2 covid19 vaccine multiple sclerosis early experience tertiary ms center israel eur j neurol 2021 jul 21 doi 101111 ene15028 online ahead printabstractbackground although covid19 vaccines currently recommended people multiple sclerosis ms fact specifically tested people ms raises uncertainty regarding safety vaccines population purpose study report reallife safety data bnt162b2 covid19 vaccine cohort ms patientsmethods anonymous survey distributed 425 ms patients participants asked general demographic diseaserelated questions specific questions regarding safety profile covid19 vaccineresults 262 425 ms patients completed questionnaire median age 42 years range 2279 years 199 females 759 66 participants 252 associated comorbidities 198 participants 756 treated diseasemodifying therapies dmts 239 participants 912 responders received bnt162b2 covid19 vaccine 182 761 55 years old 57 239 55 years old 136 participants 569 525 55 years age 403 55 years p01517 reported adverse events 36 participants 151 reported new worsening neurological symptoms following vaccination frequent sensory disturbances 21 participants 583 symptoms occurred within first 24 hours vaccination resolved within three days 28 participants 778 didnt require medication treat symptomsconclusions survey indicates overall favorable safety profile bnt162b2 vaccine people ms data confirmed prospective largescale studiespmid34288285 doi101111 ene15028,0.0
cutaneous diseases related hyperactive tcell response ocrelizumabtreated multiple sclerosis patients j neurol 2021 jun 28 doi 101007 s00415021106793 online ahead printno abstractpmid34181076 doi101007 s00415021106793,0.0
diseasemodifying therapies sarscov2 vaccination multiple sclerosis expert consensus j neurol 2021 apr 12 doi 101007 s00415021105452 online ahead printabstractcoronavirus disease covid19 appeared december 2019 chinese city wuhan quickly become global pandemic disease caused severe acute respiratory syndrome coronavirus type2 sarscov2 rna beta coronavirus phylogenetically similar sars coronavirus date 132 million cases covid19 recorded world 28 million fatal https coronavirusjhuedu maphtml huge vaccination campaign started around world since end 2020 availability vaccines raised concerns among neurologists regarding safety efficacy vaccination patients multiple sclerosis ms taking immunomodulatory immunosuppressive therapiespmid33844056 doi101007 s00415021105452,0.0
coenzyme q10 mitochondrial restorer various brain disorders naunyn schmiedebergs arch pharmacol 2021 oct 1 doi 101007 s00210021021618 online ahead printabstractcoenzyme q10 ubiquinone coq10 lipid molecule acts electron mobile carrier electron transport chain also contains antioxidant properties supplementation coq10 useful treat mitochondrial diseases coq10 along synthetic analogue idebenone used largely treat various neurodegenerative diseases including alzheimers disease parkinsons disease huntingtons disease amyotrophic lateral sclerosis friedreichs ataxia additional brain disease condition like autism multiple sclerosis epilepsy depression bipolar disorder related mitochondrial impairment article reviewed numerous physiological functions coq10 rationale use clinical practice different brain disorderspmid34596729 doi101007 s00210021021618,0.0
teriflunomide pediatric first approval paediatr drugs 2021 oct 1 doi 101007 s40272021004711 online ahead printabstractteriflunomide aubagio developed sanofi oral immunomodulatory agent targeting mitochondrial enzyme dihydroorotate dehydrogenase available adults treat relapsingremitting multiple sclerosis ms 18 june 2021 teriflunomide received first approval indication pediatric patients aged 10 years eu article summarizes milestones development teriflunomide leading first pediatric approval relapsingremitting mspmid34595696 doi101007 s40272021004711,0.0
apparent changes epidemiology severity multiple sclerosis nat rev neurol 2021 sep 28 doi 101038 s4158202100556y online ahead printabstractmultiple sclerosis ms immunological disease causes acute inflammatory lesions chronic inflammation cns leading tissue damage disability awareness ms increased options therapy come use large amount epidemiological data collected enabling studies changes incidence disease course time overall data seem indicate incidence ms increased course disease become milder particularly 25 years since first diseasemodifying therapies dmts became available clear understanding trends reasons important understanding factors influence development progression ms clinical management respect prevention treatment decisions review consider evidence changes epidemiology ms focusing trends incidence disease time trends disease severity addition discuss factors influencing trends including refinement diagnostic criteria improvements healthcare systems increased diagnosis people mild disease introduction improvement dmtpmid34584250 doi101038 s4158202100556y,0.0
cognitive central vestibular functions correlate people multiple sclerosis neurorehabil neural repair 2021 sep 2415459683211046268 doi 101177 15459683211046268 online ahead printabstractbackground cognitive impairment common poorly managed people multiple sclerosis ms balance correlated cognition people ms potentially shared utilization central sensory integration pathways objective study characterized relationship central vestibular integration cognition people ms measurement several clinical vestibular functions requiring central sensory integration multiple cognitive domains methods forty people ms 20 controls completed battery vestibular cognitive examinations targeting different central vestibular integration measures different domains cognition respectively performance measures compared people ms controls correlational analyses undertaken vestibular cognitive measures ms sample results people ms performed worse controls vestibular cognitive measures consistent correlations vestibular cognitive measures ms sample factor analysis vestibular functions yielded single factor hypothesized represent central vestibular integration demonstrated significant relationship composite cognitive measure people ms discussion results suggest vestibular cognitive dysfunction may arise central sensory processing pathways people ms connection targeted vestibular rehabilitation techniques improve central sensory processing balance cognition people mspmid34560828 doi101177 15459683211046268,0.0
periods synchronized myelin changes shape brain function plasticity nat neurosci 2021 nov 24 11 15081521 doi 101038 s41593021009172 epub 2021 oct 28abstractmyelin lipid membrane wraps axons enabling fast neurotransmission metabolic support axons conventionally thought static structure set early development however recent evidence indicates central nervous system cns myelination protracted plastic process ongoing throughout adulthood importantly myelin emerging potential modulator neuronal networks evidence human studies highlighted myelin major player shaping human behavior learning review myelin changes throughout life learning discuss potential mechanisms myelination different life stages explore whether myelin plasticity provides regenerative potential cns white matter question whether changes myelin may underlie neurological disorderspmid34711959 doi101038 s41593021009172,1.0
dopaminergic receptors neuroimmune mediators experimental autoimmune encephalomyelitis mol neurobiol 2021 aug 25 doi 101007 s12035021025076 online ahead printabstractthe dopaminergic system plays essential role maintaining homeostasis central nervous system cns immune system previous studies associated imbalances dopaminergic system pathogenesis multiple sclerosis ms examined protein levels dopaminergic receptors d1r d2r different phases experimental autoimmune encephalomyelitis eae model also investigated treatment pramipexole ppx dopamine d2 d3 receptorpreferring agonistwould able prevent eaeinduced motor mood dysfunction well underlying mechanisms action report d2r immunocontent upregulated spinal cord eae mice 14 days postinduction moreover d1r d2r immunocontents lymph nodes oxidative damage spinal cord striatum eae animals significantly increased chronic phase also presymptomatic phase axonal damage spinal cord eae mice already found surprisingly therapeutic treatment ppx failed inhibit progression eae note ppx treatment inhibited eaeinduced depressivelike failed inhibit anhedoniclike behaviors observed ppx treatment downregulated il1 levels increased bndf content spinal cord eae induction herein show d2 d3 receptorpreferred agonist mitigated eaeinduced depressivelike behavior serve new possibility clinical trials treating depressive symptoms ms patients thus infer d2r participates crosstalk cns immune system autoimmune neuroinflammatory response induced eae mainly acute chronic phase diseasepmid34432265 doi101007 s12035021025076,0.0
atrioventricular block fingolimod resumption consequence sphingosine1phosphate axis alteration due covid19 j neurol 2021 apr 14 doi 101007 s0041502110556z online ahead printabstractduring covid19 pandemic concerns raised regarding use immunosuppressants multiple sclerosis even current data support increased risk infection although fingolimod can temporarily suspended covid19 benefitrisk balance suspension can challenging till now adverse events described resumption fingolimod following previous discontinuation report occurrence atrioventricular block following fingolimod restart fingolimod acts sphingosine1phosphateaxis pathway altered covid19 hypoxic conditions herein discuss metabolic changes may influenced fingolimod pharmacology leading cardiac eventpmid33852086 doi101007 s0041502110556z,0.0
kinetics theories understand mechanism aggregation protein design strategies inhibition biophys chem 2021 aug 11 278106665 doi 101016 jbpc2021106665 online ahead printabstractprotein aggregation phenomenon closely related formation amyloids results many neurodegenerative diseases like alzheimers parkinsons huntingtons amyotrophic lateral sclerosis order prevent treat diseases clear understanding mechanism misfolding selfassembly peptides proteins crucial aggregation protein may involve various microscopic events multiple simulations utilizing solutions master equation given better understanding kinetic profiles involved presence absence particular microscopic event review focuses understanding contribution molecular events protein aggregation based analysis kinetic profiles aggregation also discuss effect inhibitors target various species aggregation pathways kinetic profile protein aggregation end review strategies inhibition aggregation can utilized combining chemical kinetics approach thermodynamics proposedpmid34419715 doi101016 jbpc2021106665,0.0
irhom1 rescues cognitive dysfunction multiple sclerosis via preventing myelin injury genes brain behav 2021 oct 21e12771 doi 101111 gbb12771 online ahead printabstractmultiple sclerosis ms characterized myelin sheath injury disintegrin metalloprotease17 adam17 disintegrin metalloproteinase essential regulating oligodendrocyte ol regeneration remyelination demyelinating conditions irhom1 highly conserved inactive protease belongs rhomboid family one key regulators adam17 maturation however unknown whether irhom1 also plays role central neuron system myelination demyelinating conditions like ms study investigated function irhom1 adam17 cognitive capability ms establishing mice irhom1 overexpression hippocampuspmid34672089 doi101111 gbb12771,1.0
gold coast diagnostic criteria implications als diagnosis clinical trial enrollment muscle nerve 2021 aug 11 doi 101002 mus27392 online ahead printabstractdiagnostic criteria amyotrophic lateral sclerosis als complex incorporating multiple levels certainty possible definite thereby prone error specifically interrater variability previously established poor thereby limiting utility diagnostic enrollment criteria clinical trials additionally different levels diagnostic certainty necessarily reflect disease progression adding confusion diagnostic algorithm realizing inherent limitations world federation neurology international federation clinical neurophysiology international alliance als mnd associations als association us motor neuron disease association convened consensus meeting gold coast australia 2019 consider development simpler criteria better reflected clinical practice merged diagnostic categories single entity diagnostic accuracy novel gold coast criteria subsequently interrogated large crosssectional study established increased sensitivity als diagnosis compared previous criteria diagnostic accuracy maintained irrespective disease duration functional status site disease onset importantly gold coast criteria differentiated atypical phenotypes primary lateral sclerosis typical als phenotype proposed gold coast criteria incorporated routine practice clinical trial settingspmid34378224 doi101002 mus27392,0.0
piperine improves experimental autoimmune encephalomyelitis eae lewis rats neuroprotective antiinflammatory antioxidant effects mol neurobiol 2021 aug 2 doi 101007 s12035021024975 online ahead printabstractinflammation demyelination glial activation oxidative damage pathological hallmarks multiple sclerosis ms piperine main bioactive alkaloid black pepper possesses antioxidant antiinflammatory neuroprotective properties whose therapeutic potential less studied experimental autoimmune encephalomyelitis eae models study efficiency piperine progression eae model myelin repair mechanisms investigated eae induced female lewis rats piperine vehicle daily administrated intraperitoneally day 8 29 post immunization found piperine alleviated neurological deficits eae disease progression luxol fast blue staining immunostaining lumbar spinal cord cross sections confirmed piperine significantly reduced extent demyelination inflammation immune cell infiltration microglia astrocyte activation gene expression analysis lumbar spinal cord showed piperine treatment decreased level proinflammatory cytokines tnf il1 inos enhanced il10 nrf2 ho1 mbp expressions piperine supplementation also enhanced total antioxidant capacity frap reduced level oxidative stress marker mda cns eae rats finally found piperine antiapoptotic neuroprotective effect eae reducing caspase3 apoptosis marker enhancing bdnf neun expressing cells study strongly indicates piperine beneficial effect eae progression considered potential therapeutic target ms treatment upcoming clinical trials will provide deeper understanding piperines role treatment mspmid34338970 doi101007 s12035021024975,1.0
secondary skin involvement classic hodgkin lymphoma results international collaborative cutaneous lymphoma working group study 25 patients j cutan pathol 2021 jun 4 doi 101111 cup14077 online ahead printabstractaims cutaneous involvement classic hodgkin lymphoma chl extraordinarily rare phenomenon current era date single large case series cutaneous involvement hodgkin lymphoma ever reported literaturemethods results total 25 cases classic hodgkin lymphoma found cases represented examples systemic chl secondary skin dissemination single lesion usually tumor nodule infiltrative plaque observed 56 cases multiple lesions present 28 cases patients 86 12 14 diagnosis stage iv disease first diagnosis interval clinical first diagnosis hl development skin lesions ranged 6108 months average 3375 months comprehensive histopathologic evaluation cases initial diagnosis revealed diagnosis classic hl otherwise specified nos 60 cases 15 25 nodular sclerosis type 24 6 25 mixed cellularity 12 3 25 lymphocyte depleted 4 1 25 conclusions provide documentation large series classic hodgkin lymphoma secondary skin involvement association chl additional clinical morphologic immunophenotypic features article protected copyright rights reservedpmid34089205 doi101111 cup14077,0.0
effects yoga inflammatory bowel diseases frequent ibdassociated extraintestinal symptoms like fatigue depression complement ther clin pract 2021 jul 29 45101465 doi 101016 jctcp2021101465 online ahead printabstractquality life qol persons inflammatory bowel diseases ibd often impaired symptoms primarily relate intestinal inflammation among challenging extraintestinal symptoms depression fatigue also frequent chronic diseases like multiple sclerosis rheumatoid arthritis cancer yoga ancient indian tradition containing postures breathing exercises meditation may positively influence symptoms review evaluates current literature regard effect yogabased interventions persons ibd regard qol depression fatigue somatic disorders systematic literature search yielded three trials examining effects yoga patients ibd 37 trials addressing depressive syndromes fatigue somatic disorders summary inperson videobased yoga classes feasible acceptable safe complementary treatment patients ibd significantly improve anxiety impaired quality life current literature provide information effect yoga depression fatigue patients ibd research somatic disorders patients depressive disorders implies potential yoga regard persons ibd specifically addressed interventional trials standardized yoga modules including patients ibd suffering fatigue depression impaired qolpmid34388560 doi101016 jctcp2021101465,0.0
cmv meningitis associated dimethyl fumarate therapyinduced lymphopenia multiple sclerosis patient j neurol 2021 jun 27 doi 101007 s0041502110661z online ahead printno abstractpmid34175973 doi101007 s0041502110661z,0.0
doubleedged effects tamoxifeninoilgavage infectious murine model multiple sclerosis brain pathol 2021 jun 17e12994 doi 101111 bpa12994 online ahead printabstracttamoxifen gavage commonly used method induce genetic modifications creloxp systems selective estrogen receptor modulator serm compound known immunomodulatory neuroprotective properties noninfectious central nervous system cns disorders can even cause complete prevention lesion development seen experimental autoimmune encephalitis eae effect infectious brain disorders scarcely investigated study susceptible sjl mice infected intracerebrally theilers murine encephalomyelitis virus tmev treated three times tamoxifeninoilgavage tog resembling application scheme genetically modified mice starting 0 18 38 days post infection dpi mice developed tmevinduced demyelinating disease tmevidd resulting inflammation axonal loss demyelination spinal cord tog positive effect numbers oligodendrocytes oligodendrocyte progenitor cells irrespective time point application whereas late application starting 38 dpi associated increased demyelination spinal cord white matter 85 dpi furthermore tog differential effects cd4+ cd8+ t cell infiltration cns especially long lasting increase cd8+ cells detected inflamed spinal cord depending time point tog application number tmevpositive cells astrogliosis astrocyte phenotype apoptosis clinical score motor function measurably affected data indicate tamoxifen gavage doubleedged effect tmevidd promotion oligodendrocyte differentiation proliferation also increased demyelination depending time point application data study suggest tamoxifen also partially protective functions infectious cns disease effects considered experimental studies using creloxp system especially models investigating neuropathologiespmid34137105 doi101111 bpa12994,1.0
bioinformatics system biology approaches identify pathophysiological impact covid19 progression severity neurological diseases comput biol med 2021 sep 23 138104859 doi 101016 jcompbiomed2021104859 online ahead printabstractthe coronavirus disease 2019 covid19 still tends propagate increase occurrence covid19 across globe clinical epidemiological analyses indicate link covid19 neurological diseases nds drive progression severity nds elucidating patients covid19 influence progression nds patients nds diagnosed covid19 becoming increasingly sick although others unclear research investigated covid19 nd interact impact covid19 severity nds performing transcriptomic analyses covid19 nds samples developing pipeline bioinformatics networkbased approaches transcriptomic study identified contributing genes filtered cell signaling pathway gene ontology proteinprotein interactions transcription factor microrna analysis identifying hubproteins using proteinprotein interactions leads identification therapeutic strategy additionally incorporation comorbidity interactions score enhances identification beyond simply detecting novel biological mechanisms involved pathophysiology covid19 nds comorbidities computing semantic similarity covid19 nd found genebased maximum semantic score covid19 parkinsons disease minimum semantic score covid19 multiple sclerosis similarly found gene ontologybased maximum semantic score covid19 huntington disease minimum semantic score covid19 epilepsy disease finally validated findings using goldstandard databases literature searches determine genes pathways previously associated covid19 ndspmid34601390 doi101016 jcompbiomed2021104859,0.0
rort protein modifications il17mediated inflammation trends immunol 2021 oct 9s14714906 21 001812 doi 101016 jit202109005 online ahead printabstractrort master transcription factor cytokine interleukin il 17 expressed explicitly th17 cells t cells type 3 innate lymphoid cells mice humans since dysregulated il17 expression strongly linked several human inflammatory diseases rortil17 axis focus intense research recently several studies shown rort modified multiple posttranslational mechanisms including ubiquitination acetylation sumoylation phosphorylation review discusses posttranslational modifications modulate rort function turnover regulate il17driven inflammation broad knowledge pathways crucial clear understanding pathogenic role rort+il17+ cells development putative therapeutic strategies target il17driven diseases multiple sclerosis psoriasis rheumatoid arthritis systemic lupus erythematosus inflammatory bowel diseasepmid34635393 doi101016 jit202109005,0.0
construction lncrnamirnamrna network determine key regulators th1#x2f th2 imbalance multiple sclerosis epigenomics 2021 nov 2 doi 102217 epi20210296 online ahead printabstractaim exact epigenetic mechanisms determine balance t helper cells 1 2 th1 th2 autoimmune responses multiple sclerosis ms remain unclear aim clarify methods combination bioinformatics analysis molecular evaluations utilized identify master hub genes results competitive endogenous rna network containing six long noncoding rnas lncrnas 21 mirnas 86 mrnas provided enrichment analysis proteinprotein interaction network neat1 malat1 found differentially expressed lncrnas using geo gse21942 quantitative realtime pcr results demonstrate dysregulation runx3 regulator th1 th2 balance gata3 tbx21 well mir544a mir2103p directly target runx3 elisa also confirmed imbalance ifn th1 il4 th2 ms patients conclusion findings introduce novel biomarkers leading th1 th2 imbalance mspmid34726075 doi102217 epi20210296,0.0
37th congress european committee treatment research multiple sclerosis ectrims 2021 1315 october 2021 pharmaceut med 2021 dec 2 doi 101007 s4029002100411x online ahead printno abstractpmid34855157 doi101007 s4029002100411x,0.0
patientpowered research networks autoimmune research collaborative rationale capacity future directions patient 2021 apr 27 doi 101007 s40271021005151 online ahead printabstractpatientpowered research networks pprns usbased registry infrastructures cocreated advocacy groups patient research partners academic investigators healthcare stakeholders patientpowered research networks collect information directly patients conduct disseminate results patientcentered powered research helps patients make informed decisions healthcare patientpowered research networks gather utilize realworld data patientreported outcomes conduct comparative effectiveness safety research leverage internet accomplish effectively efficiently four pprns focused autoimmune immunemediated conditions formed autoimmune research collaborative arthritispower rheumatoid arthritis spondyloarthritis rheumatic musculoskeletal diseases ibd partners inflammatory bowel disease iconquerms multiple sclerosis vasculitis pprn vasculitis autoimmune research collaborative aims inform healthcare decision making patients care partners stakeholders clinicians regulators payers illustrated practical applications autoimmune research collaborative constituent pprns article discusses shared capacities challenges pprn model opportunities presented collaborating across autoimmune conditions design conduct disseminate patientcentered outcomes researchpmid33904145 doi101007 s40271021005151,0.0
interpretable machine learning model explain interplay brain lesions cortical atrophy multiple sclerosis annu int conf ieee eng med biol soc 2021 nov 202137573760 doi 101109 embc4616420219629526abstractmultiple sclerosis ms common cause trauma neurological disability young adults western countries several magnetic resonance imaging mri studies demonstrated strong association presence cortical grey matter atrophy progression neurological impairment ms patients neurobiological substrates cortical atrophy ms particular relationship white matter wm cortical lesions remain unknown aim study investigate interplay cortical atrophy different types lesions ultrahigh field uhf 7 t mri including cortical lesions lesions susceptibility rim feature histopathological studies associated impaired remyelination progressive tissue destruction combined lesion characterization recent machine learning ml framework includes explainability able predict cortical atrophy ms handful lesionrelated features extracted 7 t mr imaging highlights importance uhf mri accurately evaluating intracortical rim lesion load also differential contributions types lesions may bring determine disease evolution severity also found small subset features wm lesion volume considering rim lesions patient age wm lesion count considering rim lesions intracortical lesion volume carried prediction power interestingly almost opposite pattern emerged contrasting cortical wm lesion load wm lesion load important small whereas cortical lesion load behaves opposite wayclinical relevance results suggest disconnection axonal degeneration due wm lesions local cortical demyelination main factors determining cortical thinning findings elucidate complexity ms pathology across whole brain need statistical mechanistic approaches understanding etiopathogenesis lesionspmid34892053 doi101109 embc4616420219629526,1.0
effect probiotics supplementation disease progression depression general health anthropometric measurements relapsingremitting multiple sclerosis patients systematic review metaanalysis clinical trials int j clin pract 2021 aug 11e14724 doi 101111 ijcp14724 online ahead printabstractbackground probiotics may promising role chronic autoinflammatory diseases current systematic review metaanalysis investigated effects probiotics disease progression depression general health anthropometric measurements relapsingremitting multiple sclerosis rrms patientsmethods english literature search performed using pubmed scopus web science central cochrane library january 2021 random effect models used synthesize quantitative data stata14 results total 152 identified entries four trials included quantitative synthesis n213 106 intervention 107 control additional six studies structure different markers also systematically reviewed pooled effect size showed expanded disability status scale edss wmd043 95 ci065 020 p0001 beck depression inventory bdi wmd322 95 ci438 206 p0001 general health questionnaire ghq wmd437 95 ci643 231 p0001 improved following probiotics supplementation however body weight body mass index statistically changeconclusion findings revealed probiotics supplementation can improve disease progression suppress depression general health ms patients although investigations may neededpmid34379879 doi101111 ijcp14724,0.0
vascular immunopathological role asymmetric dimethylarginine adma experimental autoimmune encephalomyelitis immunology 2021 jul 26 doi 101111 imm13396 online ahead printabstractasymmetric dimethylarginine adma endogenous nitric oxide synthase nos inhibitor uncoupler inducing vascular pathology vascular pathology important factor development progression cns pathology ms yet role adma ms remains elusive patients multiple sclerosis ms reported elevated blood levels adma mice experimental autoimmune encephalomyelitis eae animal model ms generated autoimmunization myelin oligodendrocyte glycoprotein mog bloodbrain barrier bbb disruption pertussis toxin also increased blood adma levels parallel induction clinical disease explore role adma eae pathogenesis eae mice treated daily dose adma special interest adma treatment enhanced bbb disruption eae mice exacerbated clinical cns disease eae adma treatment also induced bbb disruption eae disease mogimmunized mice even without pertussis toxin treatment suggesting role adma bbb dysfunction eae t cell polarization studies also documented adma treatment promotes th 1 th 17 mediated immune responses without affecting tregmediated immune response eae mice well invitro t cell culture taken together data first time document vascular immunopathogenic roles adma eae thus pointing potential admamediated mechanism new target potential therapy mspmid34310708 doi101111 imm13396,1.0
gray matter bloodbrain barrier water exchange dynamics reduced progressive multiple sclerosis j neuroimaging 2021 aug 6 doi 101111 jon12912 online ahead printabstractbackground purpose compare transcapillary wall water exchange putative marker cerebral metabolic health brain t2 white matter wm lesions normal appearing white gray matter nawm nagm respectively individuals progressive multiple sclerosis pms healthy controls hc methods dynamiccontrastenhanced 7t mri data obtained 19 hc 23 pms participants highresolution pharmacokinetic parametric maps representing tissue microvascular microstructural properties created shutterspeed ss paradigm modeling obtain estimates blood volume fraction vb water molecule capillary efflux rate constant kpo water capillary wall permeability surface area product pw s vb kpo linear regression models used investigate differences kpo pw s groups nawm nagm ii wm lesions nawm pmsresults highresolution parametric maps produced visualize tissue classes resolve individual wm lesions normalappearing gray matter kpo pw s significantly decreased pms compared hc p 01 twentyone t2 wm lesions analyzed 10 participants pms kpo significantly decreased wm lesions compared pms nawm p 0001 conclusions transcapillary water exchange reduced pms nagm compared hc reduced pms wm lesions suggesting pathologically impaired brain metabolism kpo provides sensitive measure cerebral metabolic activity coupling can mapped higher spatial resolution conventional imaging techniques assessing metabolic activitypmid34355458 doi101111 jon12912,0.0
contraction fatigue strength adaptations discomfort conventional versus widepulse highfrequency neuromuscular electrical stimulation systematic review appl physiol nutr metab 2021 jul 14 doi 101139 apnm20210269 online ahead printabstractneuromuscular electrical stimulation nmes can delivered conventional form convnmes using relatively widepulses highfrequencies wphfnmes wphfnmes proposed reduce contraction fatigability generate larger contractions less discomfort convnmes however systematic reviews guide selection nmes types systematic review compared effects convnmes versus wphfnmes contraction fatigability strength adaptations perceived discomfort clinical nonclinical populations eight studies included averaged across nonclinical participants individual short longterm studies either difference convnmes wphfnmes outcomes wphfnmes produced fatigability subset nonclinical participants responders however wphfnmes reduced contraction fatigability single session longterm studies found differences protocols strength adaptations nonclinical participants multiple sclerosis concluded wphfnmes reduces contraction fatigability shortterm nonclinical responder participants may exacerbate fatigability nonresponders review registered prospective international registry systematic reviews prospero registration number crd42020153907 accessed https wwwcrdyorkacuk prospero novelty bullets wphf nmes may reduce fatigue participants exacerbate fatigue others differences longterm wphf conv nmes strength adaptations future highquality research needed optimize outcomes nmesbased programspmid34260861 doi101139 apnm20210269,0.0
modeling costutility treatment sequences multiple sclerosis value health 2021 nov 24 11 16121619 doi 101016 jjval202105020 epub 2021 aug 11abstractobjectives patients multiple sclerosis ms switch diseasemodifying therapies dmts lifetime aim develop ms costutility model takes treatment switching account provide realistic estimate treatment benefit previous models assume lifetime use 1 dmtmethods treatment sequence model using microsimulation framework lifetime time horizon societal perspective developed r clinical plausibility decision rules switching defined consultation dutch ms neurologists ability dmts prevent relapses delay disease progression modeled applying dmtspecific estimates derived network metaanalysis randomized controlled trials natural history data total 2 treatment strategies compared firstline dmt sequence peginterferonglatiramerteriflunomideinterferonbetadimethyl fumarate escalation dmt sequence peginterferonglatiramerocrelizumabnatalizumabalemtuzumab scenario analyses explored impact alternative sources natural history data societal versus healthcare perspective conditionspecific versus generic utilities predicted shortterm switches 5 years externally validated dutch claims data dmt useresults shortterm switches predicted model compared well dutch claims data transition relapsingremitting ms secondary progressive ms delayed escalation sequence 247 vs 203 years firstline sequence model results sensitive utility values medical resource consumption large driver uncertaintyconclusions microsimulation model overcomes limitation previous models modeling treatment sequences better reflects clinical reality facilitates incorporating costutility information clinical guidelinespmid34711361 doi101016 jjval202105020,0.0
relative contributions obesity vitamin d leptin adiponectin multiple sclerosis risk mendelian randomization mediation analysis mult scler 2021 feb 191352458521995484 doi 101177 1352458521995484 online ahead printabstractbackground obesity associated increased risk multiple sclerosis ms however underlying mechanisms remain unclearobjective determine extent decreased vitamin d bioavailability altered levels adiponectin leptin mediate association obesity msmethods performed mendelian randomization mr analyses estimate effects ms body mass index bmi 25hydroxyvitamin d 25ohd adiponectin leptin levels cohort 14 802 ms cases 26 703 controls estimated proportion effect obesity ms explained potential mediatorsresults genetic predisposition higher bmi associated increased ms risk odds ratio 133 per standard deviation sd 95 confidence interval ci 109163 higher 25ohd levels reduced odds ms 072 per sd 95 ci 060087 contrast observed effect adiponectin leptin mr mediation analysis 52 association bmi ms attributed obesity lowering 25ohd levels 95 ci 03310 conclusions study found minority increased risk ms conferred obesity mediated lowered vitamin d levels leptin adiponectin effect consequently vitamin d supplementation modestly reverse effect obesity mspmid33605807 doi101177 1352458521995484,0.0
learning selfcatheterization prog urol 2021 aug 26s11667087 21 002104 doi 101016 jpurol202108032 online ahead printabstractsince 1970s selfcatheterization preferred method urine drainage case urinary retention neurological etiology paraplegia multiple sclerosis nonneurological cause benign prostatic hypertrophy acontractile bladder elderly subject main objective allow physiological alternation filling complete emptying phases order preserve renal function prevent urinary infections learning selfcatheterization simple requires therapeutic education session trained personnel home specialized center cognitive disorders poor vision lack dexterity lack knowledge urogenital anatomy main limitations implementation success depends frequency catheterization every 4h performed clean nonsterile manner benefit risk ratio largely favor using replace indwelling probe whenever possiblepmid34456139 doi101016 jpurol202108032,0.0
oral probiotic promotes indoleamine 2 3dioxygenase tgfproducing plasmacytoid dendritic cells initiate protection type 1 diabetes immunol lett 2021 jul 29s01652478 21 001188 doi 101016 jimlet202107009 online ahead printabstractcolonization factor antigen cfa fimbria adhesin enterotoxigenic escherichia coli confers protection murine autoimmune models type 1 diabetes t1d multiple sclerosis rheumatoid arthritis although cfa fimbriaes initial mode action bystander antigen ag independent fashion protection ultimately dependent upon induction activation autoagspecific regulatory t cells tregs however little known protection transitions bystander suppression agspecific tregs since dendritic cells dcs play integral role fate decisions t cells becoming inflammatory tolerogenic described study tests hypothesis lactococcus lactis expressing cfa llcfa stimulates dcs establish regulatory microenvironment end bone marrowderived dendritic cells bmdcs infected vitro llcfa results revealed increased production il10 tgf indoleamine 2 3deoxygenase ido although coculture llcfa infected bmdcs nave t cells promote foxp3 expression tnf ifn production suppressed nod mice orally dosed llcfa showed increase regulatory plasmacytoid dcs pdcs expressing ido tgf pancreatic lymph nodes palns spleen three days posttreatment however tregs appear mucosal inductive sites much later findings show llcfa influences specific dc populations establish tolerancepmid34333043 doi101016 jimlet202107009,0.0
liver x receptor beta deficiency attenuates autoimmuneassociated neuroinflammation t celldependent manner j autoimmun 2021 sep 1 124102723 doi 101016 jjaut2021102723 online ahead printabstractthe initiation progression autoimmune disorders multiple sclerosis ms linked aberrant cholesterol metabolism overt inflammation liver x receptors lxr nuclear receptors function crossroads cholesterol metabolism immunity activation considered promising therapeutic strategy attenuate autoimmunity however despite clear functional heterogeneity cellspecific expression profiles impact individual lxr isoforms autoimmunity remains poorly understood show lxr lxr opposite impact immune cell function disease severity experimental autoimmune encephalomyelitis model experimental ms model lxr deficiency aggravated disease pathology severity absence lxr protective guided flow cytometry using cellspecific knockout models reduced disease severity lxrdeficient mice primarily attributed changes peripheral t cell physiology occurred independent alterations microglia function collectively findings indicate lxr isoforms play functionally nonredundant roles autoimmunity potentially broad implications development lxrbased therapeutic strategies aimed dampening autoimmunity neuroinflammationpmid34481107 doi101016 jjaut2021102723,0.0
reply role neurovascular contact patients multiple sclerosis cephalalgia 2021 jul 133331024211027358 doi 101177 03331024211027358 online ahead printno abstractpmid34256649 doi101177 03331024211027358,0.0
novel microbiotarelated gene set enrichment analysis identified osteoporosis associated gut microbiota autoimmune diseases j bone miner metab 2021 aug 2 doi 101007 s0077402101247w online ahead printabstractintroduction gut microbiota now considered hidden organ interacts bidirectionally cellular responses numerous organs belonged immune bone nervous systems aimed investigate relationships gut microbiota complex diseases utilizing multiple publicly available genomewide associationmaterials methods applied novel microbiotarelated gene set enrichment analysis approach detect associations gut microbiota complex diseases processing genomewide association studies gwass data sets six autoimmune diseases including celiac disease ced inflammatory bowel diseases ibd multiple sclerosis ms primary biliary cirrhosis pbc type 1 diabetes t1d primary sclerosing cholangitis psc osteoporosis op results family oxalobacteraceae genus candidatus_soleaferrea found correlated six autoimmune diseases fdr adjusted p 005 moreover observed six autoimmune diseases except pbc shared 3 overlapping features including family peptostreptococcaceae order gastranaerophilales genus romboutsia six autoimmune diseases bmds lsbmd tbbmd association signal observed genus candidatus_soleaferrea fdr adjusted p 005 notably fa fnbmd shared maximum number overlapping microbial features eg genus ruminococcaceae_ucg009 erysipelatoclostridium ruminococcaceae_ucg013 conclusion study found part gut microbiota novel regulators bmds autoimmune diseases via effects metabolites may lead better understanding role played gut microbiota communication microbiotaskeletal immunegut axispmid34338852 doi101007 s0077402101247w,0.0
secondary immunodeficiency risk infection following immune therapies neurology cns drugs 2021 oct 16 doi 101007 s40263021008634 online ahead printabstractsecondary immunodeficiencies sids acquired conditions may occur sequelae immune therapy recent years number diseasemodifying therapies dmts approved multiple sclerosis related disorders neuromyelitis optica spectrum disorders frequently also used offlabel treat conditions chronic inflammatory demyelinating polyneuropathy cidp myasthenia gravis myositis encephalitis review focus currently available immune therapeutics neurology explore specific modes action might contribute sid particular emphasis potential induce secondary antibody deficiency considering evidence clinical trials well longterm observational studies related patients immune status risks severe infections delineate longterm anticd20 therapy greatest data availability rituximab major risk factor development sid particularly secondary antibody deficiency alemtuzumab cladribine relevant effects circulating bcell counts however evidence sid mediated antibody deficiency appears limited urgently warrants systematic evaluation date evidence suggesting treatment fingolimod dimethyl fumarate natalizumab leads antibody deficiency risk factors predisposing development sid include duration therapy increasing age preexisting low immunoglobulin ig levels prevention strategies sid comprise awareness risk factors individualized treatment protocols vaccination concepts immune supplementation employing ig replacement therapy might reduce morbidity mortality associated sids neurological conditions light broad range existing emerging therapies potential sid warrants urgent consideration among neurologists healthcare professionalspmid34657228 doi101007 s40263021008634,1.0
effects walking exercise training learning memory hippocampal neuroimaging outcomes ms targeted pilot randomized controlled trial contemp clin trials 2021 sep 5106563 doi 101016 jcct2021106563 online ahead printabstractpurpose current pilot study involved singleblind randomized controlled trial rct effects treadmill walking exercise training compared active control condition learning memory l m hippocampal neuroimaging outcomes 11 fullyambulatory persons multiple sclerosis ms demonstrated impairments new learningmethods study protocol registered clinicaltrialsgov nct03319771 february 2018 eleven fullyambulatory persons msrelated impairments new learning randomly assigned either 12weeks supervised treadmill walking exercise training 12weeks lowintensity resistive exercise active control condition participants underwent neuropsychological tests l m hippocampal neuroimaging 12week study period outcomes administered treatmentblinded assessorsresults moderatetolarge intervention effects measures verbal l m p2 011 d 063 95 ci 061 183 whereby intervention condition demonstrated improvement california verbal learning testii cvltii scores compared control condition smaller effects composite l m measure p2 002 d 028 95 ci 093 146 large intervention effects normalized hippocampal volume p2 036 d 113 95 ci 009 282 whereby hippocampal volume preserved intervention condition compared hippocampal atrophy control condition comparison intervention effects hippocampal restingstate functional connectivityconclusions collectively study provides initial proofofconcept data examining treadmill walking exercise training possible behavioral approach managing l m impairment preserving hippocampal volume common debilitating manifestations mspmid34496278 doi101016 jcct2021106563,0.0
microrna71885p mir7235 regulates multiple sclerosis experimental mouse model mol immunol 2021 sep 17 139157167 doi 101016 jmolimm202107002 online ahead printabstractthe short noncoding micrornas mirnas emerged reliable modulators various pathological conditions including autoimmune diseases mammals current study aims identify new potential differential expressed mirnas downstream mrna targets autoimmune disease multiple sclerosis ms study identifies new set mirna s probably implicated ms using computational tools study carriedout different vivo vitro experiments check identified mirnas role therapeutic prognostic applications preliminary insilico screening revealed mir6593p mir6595p mir684 mir36073p mir36075p mir36823p mir36825p mir4647 mir71883p mir71885p mir7235 specifically elevated secondary lymphoid cells eae mice addition expression downstream target mrna mirnas fxbo33 sgms1 zdhhc9 gabra3 nrxn2 reciprocal mirna expression lymphoid cells confirmed applying mimic silencing mirna models suggesting new inflammatory target genes promising mirna markers vivo adoptive transfer model revealed suppression mirna71885p mir7235 changed pattern astrocytes cns pathophysiology current study opens new mirna mrna targets ms disease absence mirna71885p mir7235 enhanced disease alleviation confirms regulatory effect targets optimized results highlights new set mirnas therapeutic potential experimental ms studies required confirm mirna therapeutic biomarkerpmid34543842 doi101016 jmolimm202107002,1.0
realworld adherence onabotulinumtoxina treatment spasticity insights aspire study arch phys med rehabil 2021 jul 7s00039993 21 004974 doi 101016 japmr202106008 online ahead printabstractobjective identify baseline characteristics treatmentrelated variables impact adherence onabotulinumtoxina treatment adult spasticity international registry aspire studydesign prospective observational registry nct01930786 setting international clinical sitesparticipants adults spasticityinterventions onabotulinumtoxina clinicians discretionmain outcome measure s clinically meaningful thresholds used treatment adherent 3 treatment sessions 2year study nonadherent 2 sessions data analyzed using logistic regression presented odds ratios 95 confidence intervals ci treatmentrelated variables assessed sessions 1 2 onlyresults total population n730 523 patients 716 treatment adherent 53 16 mean sd sessions 207 284 nonadherent 15 05 final model n626 730 522 patients 834 treatment adherent 104 166 nonadherent baseline characteristics associated adherence treated europe or184 ci106321 p0030 use orthotics or188 ci115308 p0012 baseline characteristics associated nonadherence history diplopia or028 ci009089 p0031 use assistive devices or051 ci029090 p0021 treatmentrelated variables associated nonadherence treatment interval 15 weeks or043 ci026072 p0001 clinician dissatisfaction onabotulinumtoxina manage pain or018 ci005069 p0012 stroke population n411 288 patients 701 treatment adherent 53 16 mean sd sessions 123 299 nonadherent 15 05 final stroke model n346 411 288 patients 832 treatment adherent 58 168 nonadherent baseline characteristics associated adherence treated europe or299 ci139644 p0005 use orthotics or318 ci157645 p0001 treatmentrelated variables associated nonadherence treatment interval 15 weeks or042 ci021083 p0013 moderate severe disability upper limb das pain subscale or040 ci019083 p0015 conclusions aspire analyses demonstrate realworld patient clinical variables impact adherence onabotulinumtoxina provide insights help optimize management strategies improve patient carepmid34245684 doi101016 japmr202106008,1.0
vivo evidence differential frontal cortex metabolic abnormalities progressive relapsingremitting multiple sclerosis nmr biomed 2021 jul 28e4590 doi 101002 nbm4590 online ahead printabstractthe pathophysiology progressive multiple sclerosis remains elusive significantly limiting available diseasemodifying therapies proton mrs 1 hmrs enables vivo measurement small molecules implicated multiple sclerosis application key metabolites glutamate aminobutyric acid gaba glutathione sparse employed 7 t previously validated 1 hmrs protocol measure glutamate gaba glutathione well glutamine nacetyl aspartate choline myoinositol frontal cortex individuals relapsingremitting n 26 progressive n 21 multiple sclerosis healthy control adults n 25 crosssectional analysis individuals progressive multiple sclerosis demonstrated reduced glutamate f2 65 3424 p 004 1240 062 mm versus control 1317 095 mm p 003 glutamine f2 65 0352 p 07 471 035 mm versus control 484 042 mm reduced gaba f2 65 389 p 003 129 023 mm versus control 147 025 mm p 005 possibly reduced glutathione f2 65 0352 p 0056 223 046 mm versus control 251 048 mm p 01 group multiple sclerosis patients demonstrated significant negative correlations disease duration glutamate gaba 04 p 002 glutamine glutathione alone relapsingremitting multiple sclerosis patients exhibited significant negative correlation disease duration gaba 05 p 003 taken together results indicate frontal cortex metabolism differentially disturbed progressive relapsingremitting multiple sclerosispmid34318959 doi101002 nbm4590,0.0
dengue fever multiple sclerosis patient taking ocrelizumab clinical commentary mult scler 2021 aug 2713524585211039750 doi 101177 13524585211039750 online ahead printno abstractpmid34449279 doi101177 13524585211039750,0.0
measuring treatment response advance precision medicine multiple sclerosis ann clin transl neurol 2021 oct 26 doi 101002 acn351471 online ahead printabstractobjective assess independent contributions clinical measures relapses expanded disability status scale edss scores neuroperformance measures nonclinical measures new brain magnetic resonance imaging mri activity serum neurofilament light chain snfl levels distinguishing natalizumabtreated placebotreated patientsmethods conducted post hoc analyses using data affirm trial natalizumab multiple sclerosis used multivariable regression analyses predictors edss progression relapse new enlarging mri activity brain atrophy snfl levels neuroperformance worsening identify measures independently discriminated treatment groupsresults multivariable model best distinguished natalizumab placebo new enlarging t2 gadoliniumenhancing activity mri odds ratio 95 confidence interval 72 47109 year 2 snfl levels 975th percentile 41 2662 relapses years 02 21 1530 next bestfitting model twocomponent model included mri activity snfl levels 975th percentile year 2 little difference three twocomponent modelsinterpretation nonclinical measures new mri activity snfl levels discriminate treatment placebo groups similarly better clinical outcomes composites implications patient monitoringpmid34704393 doi101002 acn351471,0.0
neuropathological variability within spectrum nmdarencephalitis ann neurol 2021 sep 25 doi 101002 ana26223 online ahead printabstractobjective describe neuropathological features nmethyldaspartate receptor nmdar encephalitis archival autopsy cohortmethods examined four autopsies patients nmdarencephalitis two patients untreated three comorbidities small cell lung cancer sclc brain posttransplant lymphoproliferative disease ptld overlapping demyelinationresults two untreated patients inflammatory infiltrates predominantly composed perivascular parenchymal cd3+ cd8 t cells cd79a+ b cells plasma cells basal ganglia amygdala hippocampus surrounding white matter hippocampi showed significant decrease nmdarimmunoreactivity correlated disease severity patient nmdarencephalitis immunosuppression kidney transplantation developed brain monomorphic ptld inflammatory changes compatible nmdarencephalitis additionally plasma cells accumulated vicinity necrotic tumor along macrophages activated microglia strongly expressed proinflammatory activation markers hladr cd68 il18 fourth patient developed demyelinating lesions setting relapse four years nmdarencephalitis lesions exhibited hallmarks classic multiple sclerosis radially expanding lesions remyelinated shadow plaques without complement immunoglobulin deposition compatible pattern demyelinationinterpretation topographic distribution inflammation patients nmdarencephalitis reflects clinical symptoms movement disorders abnormal behavior memory dysfunction inflammation dominantly observed basal ganglia amygdala hippocampus loss nmdarimmunoreactivity correlates disease severity cooccurring pathologies influence spatial distribution composition intensity inflammation may modify patients clinical presentation outcome article protected copyright rights reservedpmid34562035 doi101002 ana26223,1.0
distinguishing fatigue fatigability multiple sclerosis neurorehabil neural repair 2021 sep 2815459683211046257 doi 101177 15459683211046257 online ahead printabstractfatigue one common debilitating symptoms reported persons multiple sclerosis ms reflects feelings tiredness lack energy low motivation difficulty concentrating can measured specific instant time perception arises interoceptive networks involved regulation homeostasis ratings indicate state level fatigue likely reflect inability correct deviations balanced homeostatic state contrast trait level fatigue quantified terms work capacity fatigability can either estimated perceived fatigability measured objective fatigability clinically fatigue often quantified questionnaires require respondents estimate past capacity perform several cognitive physical psychosocial tasks retrospective estimates provide measure perceived fatigability contrast change outcome variable actual performance task provides objective measure fatigability perceived objective fatigability assess underlying construct persons ms report elevated trait levels fatigue exhibit deficits interoceptive networks insula dorsal anterior cingulate cortex including increased functional connectivity challenging tasks state trait levels fatigue reported individual can modulated reward pain pathways understanding distinction fatigue fatigability critical development effective strategies reduce burden symptom individuals mspmid34583577 doi101177 15459683211046257,0.0
expression diacylglycerol kinase isoforms correlates progression experimental autoimmune encephalomyelitis rats histochem cell biol 2021 jul 26 doi 101007 s0041802102011x online ahead printabstractmultiple sclerosis ms characterized neuroinflammation neurodegeneration whose precise processes fully understood diacylglycerol kinase dgk isozymes expressed abundantly brain immune system may regulatory targets ms study analyzed four dgk isozymes along induction peak recovery phases experimental autoimmune encephalomyelitis eae rat model ms expression dgk isozymes diacylglycerol dag pathway eae rat brainstems analyzed qrtpcr immunohistochemistry immunofluorescence double staining western blotting elisa results showed mrna content four dgk isozymes decreased significantly immunoreactivity myelin sheathes dgk neurons dgk became weaker beginning induction phase progressive increase clinical signs dgk dgk dgk mrna increased dgk mrna decreased microglia involved formation perivascular cuffing peak phase dgk dgk expressed neurons inflammatory cells dgk also positive microglia recovery phase mrna content immunoreactivity dgk isozymes generally reached normal levels moreover results revealed changes dag accumulation pkc phosphorylation almost dgk dgk mrna summary four dgk isozymes involved eae process predominant broad presence dgk dgk suggests may regulate pathological process attenuating dag pkc pathway signaling eae evolutionpmid34312706 doi101007 s0041802102011x,1.0
homebased exercise training influences gut bacterial levels multiple sclerosis complement ther clin pract 2021 jul 30 45101463 doi 101016 jctcp2021101463 online ahead printabstractbackground multiple sclerosis associated gut microbiome alterations current study aimed investigate effect homebased exercise gut bacteria people multiple sclerosis ms also examined association exerciseinduced gut bacterial modulation circulating levels inflammatory antiinflammatory cytokinesmaterials methods fortytwo people ms female male 31 11 expanded disability scale status 5 participated study divided two groups 6 months homebased exercise 5 sessions per week controls intervention following parameters assessed gut microbiota including faecalibacterium prausnitzii akkermansia muciniphila prevotella bacteroides counts cytokine levels including interleukin il 10 tumor necrosis factoralpha tnf psychosocial factors including anxiety depression fatigueresults homebased exercise significantly increased prevotella counts decreased akkermansia muciniphila counts p 005 however significant effects faecalibacterium prausnitzii bacteroides counts p 005 significant effects homebased exercise circulating cytokine levels p 005 moreover homebased exercise associated significant improvements anxiety depression p 005 however fatigue revealed significant change p 005 akkermansia muciniphila prevotella bacteroides count changes response intervention correlated changes il10 r 0052 r 067 r 055 respectively conclusion general data revealed effect exercise gut bacteria especially prevotella akkermansia muciniphila counts can probably beneficial effect ms disease pathology course however lack changes cytokines following exercise suggests possible role mechanisms modulation circulating il10 tnf levelspmid34348201 doi101016 jctcp2021101463,0.0
exercise protects hippocampal inflammation neurodegeneration experimental autoimmune encephalomyelitis brain behav immun 2021 aug 12s08891591 21 00502x doi 101016 jbbi202108212 online ahead printabstractexercise increasingly recommended supportive therapy people multiple sclerosis pwms clinical research still disclosed real benefits exercise ms disease animal studies suggest substantial beneficial effect motor disability pathological hallmarks central peripheral dysregulated immune response hippocampus core area memory formation learning brain region involved ms pathophysiology human rodent studies suggest hippocampus highly sensitive effects exercise impact ms hippocampal damage still elusive addressed effects chronic voluntary exercise hippocampal function damage experimental autoimmune encephalomyelitis eae animal model ms mice housed standard wheelequipped cages starting day immunization throughout disease course although running activity reduced symptomatic phase exercise significantly ameliorated motor disability exercise improved cognition assessed novel object recognition test nest building presymptomatic acute stages disease respectively acute phase exercise shown prevent eaeinduced synaptic plasticity abnormalities ca1 area promoting survival parvalbuminpositive pv+ interneurons attenuating inflammation indeed exercise significantly reduced microgliosis ca1 area expression tumour necrosis factor tnf microglia lesser extent hippocampal level interleukin 1 beta il1 previously shown contribute aberrant synaptic plasticity eae hippocampus notably exercise exerted precocious longlasting mitigating effect microgliosis preceded neuroprotective action likely underlying improved cognitive function observed presymptomatic acute phase eae mice overall data provide evidence regular exercise improves cognitive function synaptic neuronal pathology typically affect eae ms brainspmid34391817 doi101016 jbbi202108212,1.0
contribution common risk variants multiple sclerosis orkney shetland eur j hum genet 2021 jun 4 doi 101038 s4143102100914w online ahead printabstractorkney shetland population isolates make northern isles scotland particular interest multiple sclerosis ms research ms prevalence high scotland orkney highest global prevalence higher northerly shetland many hypotheses excess ms cases orkney investigated including vitamin d deficiency homozygosity neither found cause high prevalence ms possible excess prevalence may explained unique genetics used polygenic risk scores prs look contribution common risk variants ms analyses conducted using orcades 97 2118 cases controls viking 15 2000 cases controls generation scotland 30 8708 cases controls data sets however evidence difference msassociated common variant frequencies found three control populations aside hladrb11501 tag snp rs9271069 snp significantly higher risk allele frequency orkney 023 p value 8 1013 shetland 021 p value 23 106 mainland scotland 017 difference frequency estimated account 6 95 ci 3 8 150 observed excess cases per 100 000 individuals shetland 9 95 ci 8 11 observed 257 excess cases per 100 000 individuals orkney compared mainland scotland common variants therefore appear account little excess burden ms northern isles scotlandpmid34088990 doi101038 s4143102100914w,0.0
advanced oxidative protein products role multiple sclerosis systematic review metaanalysis mol neurobiol 2021 aug 15 doi 101007 s12035021024939 online ahead printabstractmultiple sclerosis ms autoimmunemediated disease damages central nervous system ms pathophysiological features entirely understood increase reactive oxygen species ros possibly causes myelin oligodendrocyte degeneration rosincreased production generates new compounds oxidative modifications including advanced oxidative protein products aopps aopps oxidative stress biomarkers inflammatory mediators commonly formed hypochlorous acid oxidative action albumin considering aopps accumulation produces ros induces neuronal apoptosis may represent new target drug development ms treatment possible biomarker monitor severity disease thus review aims investigate alteration aopps levels ms possible involvement patient disability second objective analyze whether drugs compounds used ms treatment modify aopps levels protocol registered prospero crd42020203268 databases search yielded 327 articles excluded 259 duplicated articles evaluated 68 articles title abstract fulltext analyzed 17 articles included 13 articles aopps levels increased nottreated ms patients furthermore increase disability status associated aopps accumulation nottreated ms patients additionally aopps levels reduced ms patients treatment therefore aopps seem play role ms pathophysiology may become new target drug development help ms diagnosis treatment followuppmid34392502 doi101007 s12035021024939,1.0
reimagining immunological dogma nat immunol 2021 oct 18 doi 101038 s41590021010465 online ahead printno abstractpmid34663980 doi101038 s41590021010465,0.0
sexspecific remodeling tcell compartment aging implications rat susceptibility central nervous system autoimmune diseases immunol lett 2021 aug 18s01652478 21 001309 doi 101016 jimlet202108003 online ahead printabstractthe incidence multiple sclerosis ms susceptibility animals experimental autoimmune encephalomyelitis eae commonly used experimental model ms decrease aging generally autoimmune diseases develop ultimate outcome imbalance damaging immune responses self regulatory immune responses keeping former control thus review agerelated changes possibly underlying balance discussed specifically considering central role t cells ms eae impact aging overall functional capacity reflecting overall count individual functional cell properties selfreactive conventional t cells tcons foxp3+ regulatory t cells tregs potent immunoregulatory suppressive cells analyzed well analysis encompasses three distinct compartments thymus primary lymphoid organ responsible elimination selfreactive t cells negative selection generation tregs compensating imperfections negative selection peripheral blood lymphoid tissues afferent compartment brain spinal cord tissues target compartment given incidence ms susceptibility animals eae greater women females agematched men males sex independent variable also considered conclusion aging sexspecific alterations balance selfreactive tcons tregs likely occur thymus afferent compartment also target compartment reflecting multifaceted changes tcell types depth understanding important envisaging effects aging also designing interventions slowdown aging without adverse effect incidence autoimmune diseasespmid34418487 doi101016 jimlet202108003,0.0
medical cannabis cannabisbased medicine show potential efficacy potential harms crosssectional comparison controls selfrated interviewerrated outcomes within danish pilot program medical cannabis complement ther clin pract 2021 aug 20 45101476 doi 101016 jctcp2021101476 online ahead printabstractbackground purpose denmark launched pilot program medical cannabis january 2018 aim establish whether medical cannabis cannabisbased medicine mc cbm superior safe compared conventional treatment regardless indications people received medicationmaterials methods people cases identified redeemed least one prescription mc cbm according nationwide unselected danish registers propensityscore matched controls indications used mc cbm potential participants contacted electronically willing participate filled various survey instruments online participants also interviewed person order investigate symptoms depression anxiety assess cognitive levels different sets analyses conducted handling potential confounders different waysresults primary analyses cases satisfied treatment controls mean sd 292 48 versus 265 45 csq p 0006 scored lower depression 33 30 versus 46 29 p 003 cases reported higher levels pain controls measured sf36 bodilypain subdomain 363 230 versus 487 301 p 001 indications worse symptoms multiple sclerosis cases compared controls reported sideeffects generally mildconclusion potential effects harms mc cbm observed randomized trials required establish true effects harms due confounding indicationpmid34425501 doi101016 jctcp2021101476,0.0
effectiveness safety alemtuzumab treatment active relapsingremitting multiple sclerosis multicenter observational study neurol sci 2021 mar 3 doi 101007 s1007202105145x online ahead printabstractobjective far limited number realworld evidence studies effectiveness safety alemtuzumab alm published relatively small number included patients aimed study efficacy safety alm realworld clinical practice two ms centers slovenia croatiamethods retrospective chart review 71 consecutive patients relapsingremitting ms treated alm 2015 till 2018 following data collected gender age disease onset disease duration alm initiation previous disease modifying therapy number relapses active mri lesions edss year prior alm initiation every year followupresults patients completed standard dosing schedule followed mean time 3211 years initiation treatment complete data 2 years treatment relapses edss mri available 48 patients 14 292 achieved neda clinical neda achieved 38 63 participants 603 year 1 24 57 421 patients achieved neda year 2 26 41 634 patients achieved neda lower edss prior starting alm independent predictor neda multivariable model adverse events occurred 58 participants 841 new safety signals identifiedconclusion according data cohort early active rrms patients conclude alm efficacy remains high realworld clinical practicepmid33660157 doi101007 s1007202105145x,0.0
efficacy fesoterodine fumarate 8 mg neurogenic detrusor overactivity due spinal cord lesion multiple sclerosis prospective study neurourol urodyn 2021 sep 9 doi 101002 nau24790 online ahead printabstractaims antimuscarinic drugs firstline choice treatment patients neurogenic detrusor overactivity ndo fesoterodine fumarate newest antimuscarinic drug limited data published use fesoterodine fumarate patients suffering neurogenic lower urinary tract dysfunction study aims determine efficacy fesoterodine fumarate patients ndo due spinal cord lesion multiple sclerosis ms methods openlabel prospective interventional study eligible patients 1880 years old scl ms ndo confirmed urodynamic study uds baseline patients underwent uds confirm ndo quality life qol assessed shortform sf qualiveen questionnaire patients received fesoterodine 8 mg day 3 months reevaluated uds sfqualiveen primary endpoint confirmation maximum detrusor pressure pdetmax reduction treatment secondary endpoints evaluation maximum bladder capacity compliance qol effect statistical analysis included wilcoxontest using spssv26results one hundred twentyfour patients completed study ninetyfive 766 scl 29 234 ms pdetmax maximum bladder capacity compliance significant reduction treatment p 001 whole group subgroup sfqualiveen revealed significant increase qol group p 001 conclusions fesoterodine fumarate 8 mg efficacious drag patients scl ms significantly decreases detrusor pressure increases bladder capacity compliance improves qolpmid34498773 doi101002 nau24790,0.0
facioscapulohumeral muscular dystrophy poliomyelitis followed multiple sclerosis quot triple troublequot case report review literature association ms muscle disorders neuromuscul disord 2021 jun 18s09608966 21 001607 doi 101016 jnmd202106006 online ahead printabstractwe describe herein triple trouble case patient affected facioscapulohumeral muscular dystrophy type 1 fshd1 previous history poliomyelitis later developed multiple sclerosis ms association muscle disorders ms uncommon fact three case reports unusual cooccurrence regard combination hypotheses raised role immunological factors genetic basis fshd1 deletion critical number macrosatellite repeats d4z4 subtelomeric region chromosome 4q35 resulting transcriptional derepression gene dux4 molecular change induce alteration immune responses likely conferring susceptibility diseases case poliomyelitis delayed fshd1 diagnosis likely acted trigger ms onset association multiple neurological disorders kept mind avoid misinterpretation symptoms diagnostic delayspmid34446310 doi101016 jnmd202106006,0.0
proinflammatory cd20+ t cells differentially affected ms therapeutics ann neurol 2021 sep 13 doi 101002 ana26216 online ahead printabstractthe frequency cd20+ t cells recently reported increased several inflammatory conditions report patients multiple sclerosis ms cd20+ t cells display distinct proinflammatory phenotype pathogenic properties anticd20 treatment virtually extinguished cd20+ t cells may important broad effectiveness dimethylfumarat dampened activity differentiated cd20+ t cells fingolimod reduced abundance part overall t cell suppressive capacity note natalizumab treatment increased frequency cd20+ effector t cells highlighting widelyused ms therapeutics affect proinflammatory t cell subset assumed pathogenic potential surprisingly differentially article protected copyright rights reservedpmid34516013 doi101002 ana26216,0.0
association ambient air pollution multiple sclerosis systemic review metaanalysis environ sci pollut res int 2021 jun 9 doi 101007 s1135602114577z online ahead printabstractrecently increasing attention paid effects air pollutants autoimmune diseases results relationship ambient air pollution multiple sclerosis ms showed variety differences thus purpose study clarify quantify relationship ambient air pollutants ms metaanalysis electronic literature search literature related research topic collected cochrane library embase pubmed till august 18 2020 according certain criteria pooled risk estimate 95 confidence intervals 95ci calculated randomeffect model analysis removing copies browsing titles abstracts reading full text 6 studies finally included results showed particulate matter pm aerodynamic diameter 10 pm10 related ms pooled hr 1058 95 ci 10501066 correlation found pm aerodynamic diameter 25 pm25 nitrogen dioxide no2 carbon monoxide co ozone o3 benzene c6h6 major road 50 m ms publication bias heterogeneity analysis results stable pm10 correlated disease ms pollution connected ms therefore important ms patients take personal protection particulate pollution avoid exposure higher levels pmpmid34109523 doi101007 s1135602114577z,0.0
indirect comparisons siponimod fingolimod ofatumumab multiple sclerosis assessing feasibility propensity score matching analyses curr med res opin 2021 aug 131 doi 101080 0300799520211968362 online ahead printabstractobjective headtohead trials comparing siponimod fingolimod ofatumumab patients multiple sclerosis ms lacking instead comparative efficacy siponimod can derived indirect treatment comparisons itcs assessed suitability itcs leveraging individual patient data relevant phase iii trials across different ms phenotypesmethods one siponimod trial patients secondary progressive ms spms four fingolimod trials three relapsingremitting ms rrms one primary progressive ms ppms two ofatumumab trials relapsing ms rms considered suitability itcs evaluated based trial design patient eligibility criteria baseline patient characteristics placebo response outcome definitions trial analyses deemed feasible conducted using onetoone propensity score matching psm results itc siponimod spms either fingolimod rrms ofatumumab rms feasible insufficient overlap key patient characteristics eg disability level relapse history differences placebo response however comparison siponimod spms fingolimod ppms feasible sufficient overlap eligibility criteria baseline characteristics onetoone psm demonstrated siponimod favored relative fingolimod time 6 3month confirmed disability progression though significantly different hazard ratio 076 95 confidence interval 048 120 pvalue 0240 hazard ratio 080 95 confidence interval 052 122 pvalue 0300 respectively conclusions trials ms clinical phenotype important determinant itc feasibility itc siponimod spms either fingolimod rrms ofatumumab rms feasible feasible comparison siponimod spms fingolimod ppmspmid34384311 doi101080 0300799520211968362,0.0
fitforpurpose based testing validation antibodies amino carboxyterminal domains cannabinoid receptor 1 histochem cell biol 2021 aug 27 doi 101007 s00418021020255 online ahead printabstractspecific selective anticb1 antibodies among powerful research tools unravel complex biological processes mediated cb1 receptor physiological pathological conditions however low performance antibodies remains major source inconsistency results different laboratories using variety techniques including commonly accepted ones antibody specificity testing identified three five commercial antibodies different regions cb1 receptor best choice specific enduse purposes specifically antibody long fragment extracellular amino tail cb1 receptor one short sequence extreme aminoterminus detected strong surface staining applied live cells whereas two different antibodies identical fragment extreme carboxyterminus cb1 receptor one upstream peptide showed acceptable performance platforms although behaved differently immunohistochemical assays depending tissue fixation procedure used showed different specificity western blot assays made particularly suitable one techniques results provide framework interpret past future results derived use different anticb1 antibodies context current knowledge cb1 receptor molecular level highlight need adequate validation specific purposes antibodies placed market also decision discontinue madepmid34453219 doi101007 s00418021020255,0.0
advances challenges nintedanib drug delivery expert opin drug deliv 2021 sep 23 doi 101080 1742524720211985460 online ahead printabstractintroduction nintedanib ntb orally administered tyrosine kinase inhibitor approved recently usfda idiopathic pulmonary fibrosis ipf systemic sclerosisassociated interstitial lung disease sscild ntb also prescribed covid19 patients associated ipf however extremely low bioavailability around 47 hence researchers attempting address drawback different approachesareas covered review article focuses enlisting formulation attempts explored researchers increase bioavailability ntb also providing meaningful insights unexplored areas formulation development targeting lymphatic system transdermal delivery patents formulation development ntb also summarizedexpert opinion ntb potential act multiple diseases still discovered extremely low bioavailability challenge dealt obtaining full benefit studies performed aiming improving bioavailability unexplored areas can used explained article however ability reproduce laboratory results scaling industry level factor taken considerationpmid34556001 doi101080 1742524720211985460,0.0
feasibility using discrete brain computer interface people multiple sclerosis annu int conf ieee eng med biol soc 2021 nov 202156865689 doi 101109 embc4616420219629518abstractaim braincomputer interfaces bcis hold promise provide people partial complete paralysis ability control assistive technology study reports offline classification imagined executed movements upper lower limb one participant multiple sclerosis people limb function deficitsmethods collected neural signals using electroencephalography eeg participants performed executed imagined motor tasks directed prompts shown screenresults participants limb function attained 70 decoding accuracy bestimagined task compared rest atleast one task comparison participant multiple sclerosis also achieved accuracies within range participants limb function lossclinical relevance one case study provided promising participant ms able achieve comparable classification seven healthy controls studies needed assess whether people suffering ms may able use bci improve quality lifepmid34892412 doi101109 embc4616420219629518,0.0
correction validity italian multiple sclerosis neuropsychological screening questionnaire neurol sci 2021 mar 11 doi 101007 s10072021051684 online ahead printno abstractpmid33704600 doi101007 s10072021051684,0.0
case neurofascin155 igg antibodyassociated combined central peripheral demyelination successfully treated anticd20 monoclonal antibody clin neurol neurosurg 2021 sep 28 210106961 doi 101016 jclineuro2021106961 online ahead printabstractcombined central peripheral demyelination ccpd infrequent entity demyelination observed central cns peripheral nervous systems pns potentially may develop due shared immune mechanism possible cooccurrence two unrelated demyelinating diseases multiple sclerosis ms chronic inflammatory demyelination polyneuropathy cidp small number cidp patients autoantibodies nodal paranodal proteins neurofascin155 nf155 nf acts cell adhesion molecule nodal paranodal proteins glial nf 155 coexists pns cns can lead combined demyelination although nf antibodypositive cidp cases case series reported number patients overt manifestations central nervous system demyelination low group response intravenous immunoglobulin ivig anti nf155 antibodypositive nf155 + cidp known poor rituximab bcelltargeted anticd20 monoclonal antibody made good progress therapy report case neurofascin155 igg antibodies related ccpd responded well rituximab nf155+ cidp usually affects young adults early administration appropriately combined immunotherapy can prevent severe disability nf antibody testing performed unresponsive patients ivig therapypmid34624826 doi101016 jclineuro2021106961,1.0
mtadv 5mer peptide suppresses chronic inflammations well autoimmune pathologies unveils new potential targetserum amyloid j autoimmun 2021 aug 11 124102713 doi 101016 jjaut2021102713 online ahead printabstractdespite existence potent antiinflammatory biological drugs eg antitnf anti il6 receptor antibodies treating chronic inflammatory autoimmune diseases costly specific cheaper oral available drugs remain unmet need expression acute phase protein serum amyloid saa dependent release proinflammatory cytokines il1 il6 tnf inflammation conversely saa induces proinflammatory cytokine secretion including th17 leading pathogenic vicious cycle chronic inflammation 5 mer peptide 5mp mtadv methioninethreoninealanineaspartic acidvaline also called amilo5mer originally derived sequence proinflammatory cd44 variant isolated synovial fluid rheumatoid arthritis ra patient human peptide displays efficient antiinflammatory effects ameliorate pathology clinical symptoms mouse models ra inflammatory bowel disease ibd multiple sclerosis ms bioinformatics qrtpcr revealed 5mp administrated encephalomyelytic mice upregulates genes contributing chronic inflammation resistance mass spectrometry proteins pulled ra synovial cell extract biotinylated 5mp showed binds saa 5mp disrupted saa assembly correlated proinflammatory activity peptide mtadv scrambled tmvad significantly inhibited release proinflammatory cytokines il6 il1 saaactivated human fibroblasts thp1 monocytes peripheral blood mononuclear cells 5mp suppresses proinflammatory il6 release saaactivated cells nonactivated cells 5mp display therapeutic activity rats saa deficient inhibit inflammations animal models ibd ms saadependent shown others saa knockout mice conclusion 5mp suppresses chronic inflammation animal models ra ibd ms saadependent animal models saaindependentpmid34390919 doi101016 jjaut2021102713,0.0
unraveling substrates cognitive impairment multiple sclerosis multiparametric structural functional mri study eur j neurol 2021 jul 13 doi 101111 ene15023 online ahead printabstractbackground cognitive impairment frequently affects multiple sclerosis ms patients however neuroanatomical correlates still need fully explored investigated contribution structural functional magnetic resonance imaging mri abnormalities explaining cognitive impairment msmethods brain dualecho diffusion tensor 3d t1weighted restingstate rs mri sequences acquired 276 ms patients 102 healthy controls using random forest analysis contribution regional white matter wm lesions wm fractional anisotropy fa abnormalities gray matter gm atrophy rs functional connectivity fc alterations cognitive impairment ms patients investigatedresults eightyfour ms patients 304 cognitively impaired best mri predictors cognitive impairment relative importance outofbag area curve auc 0795 wm lesions right superior longitudinal fasciculus 100 left anterior thalamic radiation 934 left posterior corona radiata 785 left medial lemniscus 742 left inferior longitudinal fasciculus 704 left optic radiation 687 right middle cerebellar peduncle 606 right optic radiation 535 b decreased fa splenium corpus callosum 643 left optic radiation 610 body corpus callosum 519 fornix 509 c atrophy left precuneus 914 right cerebellum crus 844 right caudate nucleus 786 left thalamus 762 left supplementary motor area 598 relevance mri measures explaining cognitive impairment confirmed crossvalidation analysis auc0765 conclusions structural damage strategic wm gm regions rs fc abnormalities explains cognitive impairment ms patientspmid34255918 doi101111 ene15023,0.0
correlations measures als respiratory function alternative fvc amyotroph lateral scler frontotemporal degener 2021 sep 30110 doi 101080 2167842120211908362 online ahead printabstractbackground ongoing longitudinal study six european sites includes 3monthly assessment forced vital capacity fvc slow vital capacity svc peak cough flow pcf sniff nasal inspiratory pressure snip aim interim analysis assess potential snip surrogate aerosol generating procedures given covid19 related restrictions methods prospective observational study patients attending six study sites kings stage 2 3 als completed baseline fvc svc snip pcf repeated assessments 3 monthly data collected march 2018 march 2020 covid19 related study suspension imposed correlations measures calculated bayesian multiple outcomes randomeffects model constructed investigate rates decline across measures results total 270 cases 828 assessments included mean age 652 154 years 326 female 60 kings stage 2 811 spinal onset fvc svc closely correlated outcomes 095 snip showed least correlation metrics 053 fvc 054 svc 060 pcf four measures significantly declined time snip bulbar onset group showed fastest rate decline discussion snip well correlated fvc svc probably examines different aspect respiratory function respiratory measures declined time differentially according site onset snip surrogate fvc svc complementary measure declining linearly differentiating spinal bulbar onset patientspmid34590504 doi101080 2167842120211908362,0.0
water content changes new multiple sclerosis lesions minimal effect determination myelin water fraction values j neuroimaging 2021 jul 26 doi 101111 jon12908 online ahead printabstractbackground purpose myelin water fraction mwf histopathologically validated vivo myelin marker mwf proportion water short t2 relative total water increases water edema inflammation may confound mwf determination multiple sclerosis ms lesions total water content twc measurement enables calculation absolute myelin water content mwc can used distinguish edema inflammation demyelination assessed influence changes total water might mwf calculating mwc values new ms lesionsmethods 3t 32echo t2 relaxation data collected monthly 6 months six relapsingremitting ms participants twc determined multiplied mwf images calculate corrected mwc images effect water content correction examined 20 new lesions comparing mean mwf mwc timeresults average lesion first appearance lesion twc increased 64 p 003 range 1 +21 mwf decreased 24 p 006 range 70 +12 mwc decreased 20 p 026 range 68 +21 relative prelesion values average twc lesions gradually decreased whereas mwf mwc remained low shape mwf mwc lesion evolution curves nearly identical differing offsetconclusion mwf mirrors mwc able monitor myelin new lesions even taking account water content increases mwc still decreased lesion first appearance attributed demyelinationpmid34310789 doi101111 jon12908,1.0
personalized medicine multiple sclerosis integrate neurofilament light chain levels decision mult scler 2021 oct 613524585211049552 doi 101177 13524585211049552 online ahead printno abstractpmid34612731 doi101177 13524585211049552,0.0
chia oil prevents chemical immunemediated inflammatory responses mice evidence underlying mechanisms food res int 2021 nov 149110703 doi 101016 jfoodres2021110703 epub 2021 sep 13abstractchia salvia hispanica l herbaceous plant used omega3 polyunsaturated fatty acid 3 pufa source presents range beneficial effects human health herein used chia oil containing 62 linolenic acid ala compound widely related antiinflammatory actions chia oil effect tested using paw edema mechanical hyperalgesia induced carrageenan ear edema induced croton oil histamine capsaicin croton oil used preventive therapeutic treatment schedules chia oil histamine capsaicin used preventive treatment schedule chia oil mechanism action investigated using nociception paw edema response induced intraplantar injection acidified saline asic activator pge2 prostaglandin pathway cinnamaldehyde trpa1 activator bradykinin bk pathway menthol trpm8 activator capsaicin trpv1 activator rtpcr inflammatory mediators trpa1 nfb ppar cox2 il6 tnf fpr2 faah magl il12a induced carrageenan nlrp3 inflammasome activation cell viability accessed later chia oil actions evaluated experimental autoimmune encephalomyelitis eae multiple sclerosis ms model chia oil showed antiedematogenic antihyperalgesic effects administered 1 h proinflammatory stimulus particularly carrageenan croton oil moreover chia oil upregulated mrna levels cox2 formyl peptide receptor 2 fpr2 reduced il6 expression spinal cord mice submitted ipl injection carrageenan interestingly chia oil mediates antinociceptive effects mice decreasing nociceptive response induced acidified saline pge2 cinnamaldehyde bradykinin menthol capsaicin eae model chia oil preventively administered attenuated eaeinduced motor deficits mechanical hyperalgesia mice suggesting valuable effect chia oil supplementation regulating inflammatory responses immune functions immunemediated inflammatory disorders imid nonetheless additional reports will need assess effect chia oil wellcontrolled clinical trials performed ms patientspmid34600695 doi101016 jfoodres2021110703,0.0
complement component 3 astrocytes mediates retinal ganglion cell loss neuroinflammation acta neuropathol 2021 sep 6 doi 101007 s00401021023664 online ahead printabstractmultiple sclerosis ms inflammatory demyelinating disease central nervous system cns characterized varying degrees secondary neurodegeneration retinal ganglion cells rgc lost ms association optic neuritis mechanisms neuronal injury remain unclear complement component c3 implicated retinal cerebral synaptic pathology may precede neurodegeneration herein examined postmortem ms retinas used mouse model experimental autoimmune encephalomyelitis eae examine role c3 pathogenesis rgc loss associated optic neuritis first show extensive c3 expression astrocytes c3+ gfap+ cells significant rgc loss rbpms+ cells postmortem retinas people ms compared retinas nonms individuals patient progressive ms remote history optic neuritis showed marked reactive astrogliosis c3 expression inner retina extending deeper layers affected eye unaffected eye study whether c3 mediates retinal degeneration utilized global c3 eae mice found less rgc loss partially preserved neurites retina compared c3+ + eae mice c3 eae mice fewer axonal swellings optic nerve reflecting reduced axonal injury changes demyelination t cell infiltration cns using c3tdtomato reporter mouse line show definitive evidence c3 expression astrocytes retina optic nerves eae mice conditional deletion c3 astrocytes showed rgc protection replicating effects seen global knockouts data implicate astrocyte c3 expression critical mediator retinal neuronal pathology eae ms consistent recent studies showing c3 gene variants associated faster rates retinal neurodegeneration human diseasepmid34487221 doi101007 s00401021023664,1.0
neurofilament light chain phase 2 clinical trial ibudilast progressive multiple sclerosis mult scler 2021 feb 261352458520986956 doi 101177 1352458520986956 online ahead printabstractbackground sensitive specific biomarkers use progressive multiple sclerosis ms established investigate neurofilament light nfl treatment response biomarker progressive msobjective evaluate whether ibudilast 100 mg day alters serum cerebrospinal fluid csf levels nfl progressive msmethods protocoldefined exploratory analysis 2year phase 2 clinical trial ibudilast progressive ms nct01982942 serum samples collected 239 subjects subset contributed csf assayed using singlemolecule assay simoa immunoassay mixed model repeated measurements yielded log nfl response variableresults geometric mean baseline serum nfl 319 288 pg ml placebo ibudilast groups respectively geometric mean baseline csf nfl 11508 12903 pg ml placebo ibudilast groups respectively serum csf nfl correlations r 052 r 078 weeks 48 96 respectively 96 weeks betweengroup difference nfl either serum p 076 csf p 046 controlling factors may affect nfl effect ibudilast nfl either serum csf observedconclusion ibudilast treatment associated change either serum csf nflpmid33635141 doi101177 1352458520986956,0.0
c9orf72 alsftd recent evidence dysregulation autophagylysosome pathway multiple levels autophagy 2021 feb 26117 doi 101080 1554862720211872189 online ahead printabstractamyotrophic lateral sclerosis als frontotemporal dementia ftd two clinically distinct classes neurodegenerative disorders yet share range genetic cellular molecular features hexanucleotide repeat expansions hres c9orf72 gene accumulation toxic protein aggregates nervous systems affected individuals among common features though mechanisms hres cause toxicity clear toxic gain function due transcribed hre rna dipeptide repeat proteins dprs produced repeatassociated nonaug translation together reduction c9orf72 expression proposed contributing factors disease pathogenesis als ftd addition several recent studies point toward alterations protein homeostasis one root causes disease pathogenesis review discuss effects c9orf72 hre autophagylysosome pathway based various recent findings suggest dysfunction autophagylysosome pathway synergizes toxicity c9orf72 repeat rna dprs drive disease pathogenesisabbreviation alp autophagylysosome pathway als amyotrophic lateral sclerosis ampk ampactivated protein kinase atg autophagyrelated aso antisense oligonucleotide c9orf72 c9orf72smcr8 complex subunit denn differentially expressed normal neoplastic cells dpr dipeptide repeat protein eif2a eif2 eukaryotic translation initiation factor 2a er endoplasmic reticulum ftd frontotemporal dementia gap gtpaseactivating protein gef guanine nucleotide exchange factor hre hexanucleotide repeat expansion ipsc induced pluripotent stem cell isr integrated stress response m6pr mannose6phosphate receptor cation dependent map1lc3 lc3 microtubule associated protein 1 light chain 3 mn motor neuron mtorc1 mechanistic target rapamycin kinase complex 1 nd neurodegenerative disorder ran repeatassociated nonatg rb1cc1 fip200 rb1 inducible coiledcoil 1 slc66a1 pqlc2 solute carrier family 66 member 1 smcr8 smcr8c9orf72 complex subunit sqstm1 p62 sequestosome 1 stx17 syntaxin 17 tardbp tdp43 tar dna binding protein tbk1 tank binding kinase 1 tfeb transcription factor eb ulk1 unc51 like autophagy activating kinase 1 ups ubiquitinproteasome system wdr41 wd repeat domain 41pmid33632058 doi101080 1554862720211872189,0.0
fatigue insomnia daytime sleepiness multiple sclerosis versus narcolepsy acta neurol scand 2021 jul 19 doi 101111 ane13497 online ahead printabstractobjectives multiple sclerosis ms fatigue prevalent cause impaired ability work narcolepsy daytime sleepiness main symptom studies indicate fatigue present aimed assess fatigue associated features patients ms narcolepsy healthy controls assess whether clinical parameters separate fatigued msf nonfatigued ms patients msnof materials methods noninterventional crosssectional study recruited 34 ms patients 15 narcolepsy type 1 patients 17 healthy controls interviewer administered fatigue severity scale fss insomnia severity index isi epworth sleepiness scale patient health questionnaire9 saltingrimby physical activity level scale information clinical parameters current treatments collectedresults fatigue profile msf resembled narcolepsy group rather msnof resembled healthy control group isi alone significantly associated fss msnof healthy controls msf narcolepsy group variable associated fss months since diagnosis clinical variable significantly separating msf msnof ms disease duration correlated fatigue clinical variables correlated fatigue narcolepsy groupconclusions fatigued ms patients resemble narcolepsy patients resemble nonfatigued ms patients resemble healthy controls insomnia main factor associated fatigue ms disease duration clinical variable separating fatigued nonfatigued ms patients fatigued patients variance fatigue explained insomnia daytime sleepiness depression level exercisepmid34278566 doi101111 ane13497,0.0
insights knowledge complex diseases environmental infectious#x2f toxic agents potential etiopathogenetic factors systemic sclerosis j autoimmun 2021 sep 30 124102727 doi 101016 jjaut2021102727 online ahead printabstractsystemic sclerosis ssc connective tissue disease secondary three cardinal pathological features immunesystem alterations diffuse microangiopathy fibrosis involving skin internal organs etiology ssc remains quite obscure may encompass multiple host genetic environmental infectious chemicalfactors present review focused potential role environmental agents etiopathogenesis ssc based epidemiological clinical laboratory investigations previously published world literature among infectious agents viruses may persist reactivate infected individuals namely human cytomegalovirus hcmv human herpesvirus6 hhv6 parvovirus b19 b19v retroviruses proposed potential causative agents ssc viruses share number biological activities consequent pathological alterations endothelial dysfunction fibroblast activation moreover acute worsening preexisting interstitial lung involvement observed ssc patients symptomatic sarscov2 infection might suggest potential role virus overall disease outcome variety chemical occupational agents might regarded putative etiological factors ssc setting ssc complicating silica dust exposure represents one promising models study considering complexity ssc pathogenesis none suggested causative factors may explain appearance whole ssc likely disease result multifactorial multistep pathogenetic process variable combination potential etiological factors may modulate appearance different clinical phenotypes detectable individual scleroderma patients indeep investigations ssc etiopathogenesis may provide useful insights broad field human diseases characterized diffuse microangiopathy altered fibrogenesispmid34601207 doi101016 jjaut2021102727,0.0
time trends chronic immune diseases year birth danish registries eur j epidemiol 2021 sep 26 doi 101007 s1065402100804x online ahead printabstractchronic immune diseases often reported rise speculated share early life risk factors investigated year birth common denominator time trends using consistent data source danish national patient registry 35 years nationwide coverage observational nationwide birth cohort registry study persons born denmark since 1953 investigated chronic immune diseases per person years risk outcomes defined inpatient hospitalizations prechosen age bins year birth 5 year bins population 38 million persons born denmark since 1953 investigated total sum 68 million person years ages 534 years found increasing trends year birth juvenile arthritis age 1014 adult asthma age 2024 inflammatory bowel diseases age 2024 multiple sclerosis age 2529 whereas type 1 diabetes age 1519 declining birth year mid 1980s followed subsequent increase childhood asthma age 59 inpatient hospitalizations relatively stable time nationwide introduction measles mumps rubella vaccine 1987 alter trends hospitalization chronic immune diseases adult asthma juvenile arthritis inflammatory bowel diseases multiple sclerosis showed general increasing trend birth year recent 35 years diabetes 1 childhood asthma seemed stable period results affected introduction vaccinations major childhood viral infectionspmid34564794 doi101007 s1065402100804x,0.0
neuromyelitis optica spectrum disorder nmosd associated cancer systematic review mult scler relat disord 2021 aug 27 56103227 doi 101016 jmsard2021103227 online ahead printabstractnmosd disease shown highly associated diseases autoimmune diseases reports association cancer systematic review aimed obtain broad understanding cancers associated nmosd including source common perceptions assumptions regardmethods study systematically searched pubmed embase scopus web sciences proquest ovid conference proceedings reference lists retrieved articles nmosd cases met last version criteria diagnosis reported patients history cancer onset neurological symptoms without time limitations referred paraneoplastic neuromyelitis optica articles published english language abstract full text assessed finally study critically appraisedresults 47 studies met inclusion criteria assessed qualitative synthesis considering euro network criteria 62 cases met issue mean age 5221 1714 5216 1721 reported cancer nmosd cases female predominance 79 respectively reported organ cancer population genitourinary n 14 223 breast n 12 194 lung n 12 193 gastrointestinal n 7 113 hematology n 6 97 respectivelyconclusion older nmosd patients without suspicious symptoms recommend paying attention lung breast genitourinary especially ovary cancer screening also cancer resection positive effect attack numbers receiving treatment nmosd recoverypmid34536774 doi101016 jmsard2021103227,0.0
correction optic neuritis german children clinical findings association multiple sclerosis graefes arch clin exp ophthalmol 2021 sep 15 doi 101007 s00417021053435 online ahead printno abstractpmid34524499 doi101007 s00417021053435,0.0
molecular mechanisms mesocotyl elongation induced brassinosteroid maize deepseeding stress rnasequencing microstructure observation physiological metabolism genomics 2021 aug 26s08887543 21 003360 doi 101016 jygeno202108020 online ahead printabstractdeepseeding important way improve maize drought resistance mesocotyl elongation can significantly enhance seedling germination improve understanding transcriptionmediated maize mesocotyl elongation deepseeding stress rnasequencing used identify differentially expressed genes degs deepseeding tolerant w64a intolerant k12 mesocotyls following culture 10 days 20 mgl1 24epibrassinolide ebr induced stress depths 3 20 cm phenotypically mesocotyl length maize significantly increased 20 cm stress presence ebr microstructure observations revealed mesocotyls underwent programmed cell death deepseeding stress alleviated ebr found regulated multiple degs encoding cysteine protease senescencespecific cysteine protease aspartic protease family protein phospholipase d etc transcription factors tfs myb nac additionally degs associated cell wall components ie cellulose synthase cellulose synthase like protein cesa csl fasciclinlike arabinogalactan apg leucinerich repeat protein lrr lignin biosynthesis enzymes including phenylalanine ammonialyase sadenosyllmethioninedependent methyltransferases 4coumaratecoa ligase cinnamoyl coa reductase cinnamyl alcohol dehydrogenase catalase peroxiredoxin peroxidase found control cell wall sclerosis moreover auxin ethylene brassinosteriod cytokinin zeatin abscisic acid gibberellin jasmonic acid salicylic acid signaling transduction pathways corresponding degs activated inhibited tfs arf bzr1 2 barr aarr myc2 abf tga synthesis phytohormonesrelated metabolites findings provide information molecular mechanisms controlling maize deepseeding tolerance will aid breeding deepseeding maize varietiespmid34455034 doi101016 jygeno202108020,0.0
cellular humoral immune responses following sarscov2 mrna vaccination patients multiple sclerosis anticd20 therapy nat med 2021 sep 14 doi 101038 s41591021015072 online ahead printabstractsarscov2 messenger rna vaccination healthy individuals generates immune protection covid19 however little known sarscov2 mrna vaccineinduced responses immunosuppressed patients investigated induction antigenspecific antibody b cell t cell responses longitudinally patients multiple sclerosis ms anticd20 antibody monotherapy n 20 compared healthy controls n 10 bnt162b2 mrna1273 mrna vaccination treatment anticd20 monoclonal antibody acd20 significantly reduced spikespecific receptorbinding domain rbd specific antibody memory b cell responses patients effect ameliorated longer duration last acd20 treatment extent b cell reconstitution contrast patients ms treated acd20 generated antigenspecific cd4 cd8 t cell responses vaccination treatment acd20 skewed responses compromising circulating follicular helper t tfh cell responses augmenting cd8 t cell induction preserving type 1 helper t th1 cell priming patients ms treated acd20 lacking antirbd igg severe defect circulating tfh responses robust cd8 t cell responses data define nature sarscov2 vaccineinduced immune landscape acd20treated patients provide insights coordinated mrna vaccineinduced immune responses humans findings implications clinical decisionmaking public health policy immunosuppressed patients including treated acd20pmid34522051 doi101038 s41591021015072,0.0
irisin levels serum cerebrospinal fluid patients multiple sclerosis expression distribution irisin experimental autoimmune encephalomyelitis clin exp immunol 2021 aug 24 doi 101111 cei13656 online ahead printabstractirisin novel hormonelike myokine plays important role central nervous system cns diseases cerebral ischaemia alzheimers disease however irisin rarely investigated multiple sclerosis ms typical inflammatory demyelinating disease cns experimental autoimmune encephalomyelitis eae typical model ms determined levels irisin serum cerebrospinal fluid patients ms expression histological distribution irisin determined eae serum irisin levels patients ms eae mice increased levels fndc5 irisin mrna decreased spinal cord brain regardless onset peak chronic phase eae immunofluorescence staining showed colocalization irisin neurons levels irisin fluctuated disease progression ms eae irisin may involved pathological process ms eaepmid34428306 doi101111 cei13656,1.0
b cells just antibodies sarscov2 vaccine responses lancet rheumatol 2021 sep 7 doi 101016 s26659913 21 002800 online ahead printno abstractpmid34514435 pmcpmc8423428 doi101016 s26659913 21 002800,0.0
neurogenic overactive bladder focus cognitive function urologiia 2021 nov 5 3540abstractbackground overactive bladder cognitive impairment two medical social problems outmost importance affecting quality life disorders common practice urologist neurologist internist physicians parkinsons disease multiple sclerosis common neurological diseases often manifest pelvic dysfunction cognitive dysfunction clinician needs understand pathogenesis underlying disease pharmacologic properties drugs can used neurology urology well related specialtiesaim evaluate cognitive functions patients neurogenic overactive bladder treated trospium chloridematerials methods total 45 patients neurological disease 28 parkinsons disease group 1 17 multiple sclerosis group 2 included study patients symptoms overactive bladder trospium chloride administered individually adjusted dose 12 weeks cognitive functions assessed using international montreal cognitive assessment moca therapy change total scores time assessed using paired wilcoxon test level significance 005 used confidence level 95 results significant decrease studied parameters overactive bladder groups seen baseline evaluation total score moca scale prior start taking trospium chloride revealed presence moderate cognitive impairment 213+ 29 points patients group 1 12 weeks therapy significant change cognitive functions observed 217+ 31 points p005 group 2 moderate cognitive impairment moca 225+ 37 points found baseline taking trospium chloride significant changes noted moca 229+ 41 points p005 central nervous system side effects reported groupconclusion trospium chloride effective drug affect cognitive functions patients neurogenic overactive bladder drug safe use parkinsons disease multiple sclerosis considering low risk cognitive impairment polypharmacypmid34743429,0.0
exploring new frontiers multiple sclerosis nat rev drug discov 2021 oct 5 doi 101038 d4157302100170z online ahead printno abstractpmid34611330 doi101038 d4157302100170z,0.0
multiple sclerosis treatment optimization program ann clin transl neurol 2021 oct 18 doi 101002 acn351472 online ahead printabstractobjective design implement health system level intervention reduce escalating multiple sclerosis ms disease modifying treatment dmt expenditures improve outcomesmethods conducted stakeholder meetings reviewed pharmacy utilization data abstracted information subsets persons ms pwms electronic health record identify gaps barriers improving quality affordability ms care kaiser permanente southern california results informed development implementation ms treatment optimization program mstop results two main gaps identified underprescribing highly effective dmts het 49 preferred formulary dmt 209 among dmttreated pwms main barriers identified prescribers fear rare serious het side effects lack msspecific health systems science knowledge pharma influence evidence gaps formulary decisionsbased solely costs multidirectional mistrust neurologists practice leaders health plan pharmacists overcome barriers mstop developed four strategies 1 riskstratified treatment algorithm increase use hets 2 expertled ethical costsensitive riskstratified preferred formulary 3 proactive counterlaunch campaigns minimize uptake new lowvalue dmts 4 discontinuation ineffective dmts progressive nonrelapsing ms multicomponent mstop implemented education training expanding access mstrained providers audit feedback continual evidence reviewsinterpretation causes wasteful spending ms dmts complex require multiple strategies resolve provide herein granular details designed implemented health system intervention facilitate adaption settings conditionspmid34662494 doi101002 acn351472,0.0
positron emission tomography multiple sclerosis straight target nat rev neurol 2021 sep 20 doi 101038 s41582021005371 online ahead printabstractfollowing impressive progress treatment relapsingremitting multiple sclerosis ms major challenge ahead development treatments prevent delay irreversible accumulation clinical disability progressive forms disease substrate clinical progression neuroaxonal degeneration deep understanding mechanisms underlie process precondition development therapies progressive ms pet imaging involves use radiolabelled compounds bind specific cellular metabolic targets thereby enabling direct vivo measurement several pathological processes approach can provide key insights clinical relevance processes chronological sequence disease course review focus contribution pet making understanding extraneuronal intraneuronal mechanisms involved pathogenesis irreversible neuroaxonal damage ms consider major challenges use pet ms steps necessary realize clinical benefits technique addition discuss potential emerging pet tracers future applications existing compounds facilitate identification effective neuroprotective treatments patients mspmid34545219 doi101038 s41582021005371,1.0
subspecialty training neurology residents junior neurologists baltic states eur j neurol 2021 jun 15 doi 101111 ene14978 online ahead printabstractbackground neurology field increasing subspecialization published data regarding proportion neurology subspecialists baltic states aim crosssectional study identify factors associated neurology subspecialty choice examine possible differences neurology residents junior neurologists view subspecialty assess perceived subspecialty acquisition opportunities subspecialty attractivenessmethods research conducted anonymous online survey december 28 2020 january 24 2021 neurology residents neurologists completed residency last 5 years baltic statesresults total 72 residents 65 neurologists participated cerebrovascular diseases multiple sclerosis autoimmune diseases nervous system rated two attractive subspecialties residents whereas headache clinical neurophysiology attractive among junior neurologists vertigo dizziness dementia ranked least attractive among groups cerebrovascular diseases perceived acquisition opportunities two common determinants subspecialty choice medical content subspecialty influence mentor undergraduate studies residency conclusions twothirds junior neurologists subspecialize least one subspecialty onethird residents already determined pursue subspecialty training junior neurologists rated outpatientrelated subspecialties attractive neurology residents baltic states universities significant difference number residents determined pursue subspecialty trainingpmid34129702 doi101111 ene14978,0.0
dengue fever multiple sclerosis patient taking ocrelizumab mult scler 2021 aug 2713524585211030214 doi 101177 13524585211030214 online ahead printabstractdengue fever df endemic infectious disease tropical subtropical regions ocrelizumab humanized monoclonal antibody targets cd20 antigen b cells approved treatment relapsingremitting multiple sclerosis rrms primaryprogressive multiple sclerosis ppms describe favorable clinical outcome df rrms patient treated ocrelizumab neither presented hemorrhagic systemic shock symptoms reported neurological worseningpmid34449289 doi101177 13524585211030214,0.0
epithelial barrier hypothesis explain increase allergy autoimmunity chronic conditions nat rev immunol 2021 apr 12 doi 101038 s41577021005387 online ahead printabstractthere steep increase allergic autoimmune diseases reaching epidemic proportions now affecting one billion people worldwide diseases common industrialized countries prevalence continues rise developing countries parallel urbanization industrialization intact skin mucosal barriers crucial maintenance tissue homeostasis protect host tissues infections environmental toxins pollutants allergens defective epithelial barrier demonstrated allergic autoimmune conditions asthma atopic dermatitis allergic rhinitis chronic rhinosinusitis eosinophilic esophagitis coeliac disease inflammatory bowel disease addition leakiness gut epithelium also implicated systemic autoimmune metabolic conditions diabetes obesity multiple sclerosis rheumatoid arthritis systemic lupus erythematosus ankylosing spondylitis autoimmune hepatitis finally distant inflammatory responses due leaky gut microbiome changes suspected alzheimer disease parkinson disease chronic depression autism spectrum disorders article introduces extended epithelial barrier hypothesis proposes increase epithelial barrierdamaging agents linked industrialization urbanization modern life underlies rise allergic autoimmune chronic conditions furthermore discusses immune responses dysbiotic microbiota cross damaged barrier may involved development diseasespmid33846604 doi101038 s41577021005387,0.0
impact maternal autoimmune disease cellfree dna test characteristics j obstet gynecol mfm 2021 aug 18100466 doi 101016 jajogmf2021100466 online ahead printabstractbackground maternal biologic factors can affect fetal fraction cellfree dnabased prenatal screening assays thereby limiting effectiveness higher rates indeterminate results low fetal fraction described cases autoimmune disease pregnancy existing studies confounded concomitant maternal use anticoagulants may independently influence test characteristicsobjective s evaluate differences fetal fraction indeterminate results total cellfree dna concentration women autoimmune disease compared controls using inhouse developed noninvasive prenatal screening platform absence maternal anticoagulation usestudy design retrospective single institution cohort study previously validated cellfree dnabased noninvasive prenatal screening assay using lowpass whole genome sequencing platform 2017 2019 diagnosis autoimmune disease included systemic lupus erythematosus rheumatoid arthritis multiple sclerosis inflammatory bowel disease others immunomodulator therapies included biologics corticosteroids hydroxychloroquine azathioprine intravenous immunoglobulin women anticoagulation excluded evaluated association autoimmune disease fetal fraction indeterminate results total cellfree dna concentration using univariate multivariate analyses stratifying immunomodulator therapy adjusting body mass index fetal sex gestational age sample collectionresults 1 445 patients met inclusion criteria fortythree women confirmed autoimmune disease 25 immunomodulator therapy 18 immunomodulator therapy mean fetal fraction women autoimmune disease significantly lower compared controls 97 vs 119 p0004 rate indeterminate results significantly higher women autoimmune disease compared controls 163 vs 35 p0001 total cellfree dna concentration statistically different groups 948 pg ul autoimmune disease vs 839 pg ul controls p006 logistic regression women autoimmune disease significantly higher odds indeterminate result compared controls aor 53 95ci 20 142 linear regression showed significant negative association autoimmune disease fetal fraction 21 95ci 34 06 stratifying treatment status mean fetal fraction 98 96 119 women autoimmune disease immunomodulator therapy autoimmune disease immunomodulator therapy controls respectively p002 rate indeterminate results increased stepwise fashion 35 111 200 controls autoimmune disease immunomodulator therapy autoimmune disease immunomodulator therapy respectively p0001 logistic regression demonstrated higher odds indeterminate result women autoimmune disease immunomodulator therapy compared controls aor 73 95ci 23 225 autoimmune disease immunomodulator therapy negatively associated fetal fraction compared controls 22 95ci 42 03 conclusion s women autoimmune disease lower fetal fraction higher rates indeterminate results compared women without autoimmune disease difference total cellfree dna concentration treatment maternal autoimmune disease immunomodulator therapy may decrease indeterminate result ratepmid34418590 doi101016 jajogmf2021100466,0.0
epidemiology staphylococcus aureus camrsa usa300 belgium eur j clin microbiol infect dis 2021 jun 23 doi 101007 s10096021042863 online ahead printabstractthe methicillinresistant staphylococcus aureus mrsa sequence type st 8 pantonvalentine toxin pvl positive usa300 clone worldwide distribution usa300 north american na variant harbouring arginine catabolic mobile element acme predominant usa latin american lv variant predominant northern south america variants failed become endemic europe examined epidemiology usa300 clone belgium 2006 2019 total 399 clonal complex 8 pvlpositive mrsa isolates received 2006 2019 belgian national reference laboratory s aureus investigated presence acme selected acmepositive n102 acmenegative n16 isolates sequenced characterized presence several resistance virulence molecular markers subjected phylogenetic analysis total 300 isolates usa300na acmepositive 99 acmenegative usa300na interspersed phylogeny analysis isolates countries suggesting multiple introductions however two big clades maintained spread decade peaking 2010 2017 finally decrease acmenegative isolates mainly related trips south america identified usa300lv remaining acmenegative isolates st8 sccmec ivb st923 sccmec iva col923 two clades usa300na clone successfully spread belgium seem currently decrease related south american variants detected first time belgium including emerging col923 clonepmid34160741 doi101007 s10096021042863,0.0
evobrutinib covalent bruton#39 s tyrosine kinase inhibitor mass balance elimination route metabolism healthy participants clin transl sci 2021 aug 10 doi 101111 cts13108 online ahead printabstractthe highly selective covalent brutons tyrosine kinase inhibitor evobrutinib investigation treatment patients multiple sclerosis ms early clinical studies healthy participants patients relapsing ms indicated evobrutinib welltolerated effective undertook mass balance study six men received single 75mg oral dose evobrutinib containing 36 mbq 100 ci 14 cevobrutinib determine absorption metabolic pathways routes excretion evobrutinib primary objectives phase study nct03725072 1 determine rates routes total radioactivity excretion including mass balance total drugrelated radioactivity urine feces 2 assess pharmacokinetics pks total radioactivity blood plasma 3 characterize plasma pks evobrutinib exploratory end points included identifying quantifying evobrutinib metabolites plasma excreta urine feces exploring key biotransformation pathways clearance mechanisms evobrutinib primarily eliminated feces arithmetic mean percentage sd 710 21 lesser extent urine 206 20 total radioactivity 853 excreted first 72 h administration unchanged evobrutinib detected excreta evobrutinib rapidly absorbed substantially metabolized upon absorption one major metabolite m4632 msc2430422 identified plasma 10 total drug exposure threshold classifies m4632 msc2430422 major metabolite according us food drug administration fda metabolites safety testing mist european medicines agency ema international conference harmonization ich m3 results support development evobrutinib may help inform subsequent investigationspmid34374206 doi101111 cts13108,0.0
visualization tool assessment spinal cord functional magnetic resonance imaging data quality annu int conf ieee eng med biol soc 2021 nov 202133913394 doi 101109 embc4616420219630903abstractfunctional magnetic resonance imaging fmri extensively used neuroimaging technique noninvasively detect neural activity data quality highly variable fmri analysis typically consists number complex processing steps crucial visually assess images throughout analysis ensure data quality step satisfactory fmri analysis brain simple tool visualize fourdimensional data twodimensional plot qualitative analysis despite practicality method directly applied fmri data spinal cord comparable approach exist spinal cord fmri analysis additional challenges encountered spinal cord imaging including small size cord influence physiological noise sources drive importance developing similar visualization technique spinal cord fmri introduce highly versatile image analysis tool visualize spinal cord fmri data simple heatmap covisualize relevant traces physiological motion timeseries present multiple variations plot data features can identified heatmap examples useful qualitative analyses can performed using method spinal cord plot can easily integrated fmri analysis pipeline can streamline visual inspection qualitative analysis functional imaging dataclinical relevance implementation data visualization method simple addition spinal cord fmri analysis used identify normal vs abnormal signal variation pathologies impact cord spinal cord injury multiple sclerosispmid34891967 doi101109 embc4616420219630903,0.0
prediction treatment outcomes multiple sclerosis challenges recent advances expert rev clin immunol 2021 sep 27 doi 101080 1744666x20211986005 online ahead printabstractintroduction multiple sclerosis ms chronic autoimmune neurodegenerative disease central nervous system course dependent early treatment response increasing evidence also suggests despite eliminating disease activity relapses lesions many patients continue accrue disability highlighting need comprehensive definition treatment success optimizing disability outcome measures well continuously improving understanding neuroinflammatory neurodegenerative biomarkers requiredareas covered review describes challenges inherent classifying monitoring disease phenotype ms review also provides assessment clinical radiological blood biomarker tools current future practiceexpert opinion emerging mri techniques standardized patient outcome assessments will increase accuracy initial diagnosis understanding disease progressionpmid34570656 doi101080 1744666x20211986005,0.0
age hypertension onset multiple sclerosis patients mult scler 2021 mar 1813524585211003016 doi 101177 13524585211003016 online ahead printabstractbackground objective hypertension htn common multiple sclerosis ms associated poorer outcomes sought characterize htn age onset aao ms statusmethods results 130 050 incident htn patients among 892 ms patients conducted multivariable linear regression adjusting patient attributes sex racestratified models conducted htn aao differ patients without ms p 017 similar null associations observed sex racespecific analysesconclusion complex relationships htn ms differences htn aao ms statuspmid33733922 doi101177 13524585211003016,0.0
characterization alexithymia clinically isolated syndrome rev neurol paris 2021 jun 26s00353787 21 005713 doi 101016 jneurol202101017 online ahead printabstractbackground multiple sclerosis ms prevalence alexithymia defined inability identify describe emotions close 50 prevalence symptom clinically isolated syndrome cis unknown characterizing alexithymia early stage disease can help clarify psychobehavioural disturbances cis patientsmethods forty cis patients fulfilled mri criteria dissemination space matched 40 healthy subjects completed selfassessment scales alexithymia depression anxiety apathy empathy cognitive functions assessed using battery neuropsychological testsresults mean delay standard deviation occurrence cis inclusion study 39 28 months frequency alexithymia higher cis patients controls prevalence 42 p00001 alexithymia correlated anxiety depression cognition alexithymia dependent depression p0003 conclusion alexithymia characterized difficulty identifying feelings present patients early stage ms seems strongly associated depression difficulty social interaction risk future affective disorderspmid34187691 doi101016 jneurol202101017,0.0
prevalence pain amyotrophic lateral sclerosis systematic review metaanalysis amyotroph lateral scler frontotemporal degener 2021 mar 4110 doi 101080 2167842120211892765 online ahead printabstractobjectives physical pain known symptom amyotrophic lateral sclerosis als systematically derived prevalence estimate available aim study determine pooled prevalence pain als relative method measurement pain characteristics methods systematic search across multiple databases conducted january 16 2020 randomeffects metaanalyses single proportions performed prevalence data heterogeneity determined using i2 statistic available pain location intensity type source compared results 2552 articles identified twentyone eligible studies included studies used observational designs 14 crosssectional 6 cohort 1 casecontrol pooled prevalence pain als across studies 60 95 ci 5069 high degree heterogeneity i2 94 p 001 studies used validated measures lower heterogeneity i2 82 p 0002 compared used tailored measures tailored supplemented validated measures i2 90 p 0001 i2 83 p 0001 respectively subset studies n 9 commonly reported pain location upper limbs including shoulders extremities 415 study subset n 7 showed moderatesevere intensity pain frequently reported type pain commonly related cramp spasm conclusions experiencing physical pain als occurs high prevalence deriving consensus specific tools used assess monitor compare symptoms pain population will reduce current heterogeneity approaches increase likelihood ameliorating distressing experiences effectivelypmid33661072 doi101080 2167842120211892765,0.0
assessment optic nerve optic disc perineural area using shearwave elastography patients multiple sclerosis int j clin pract 2021 aug 15e14736 doi 101111 ijcp14736 online ahead printabstractpurpose observe describe stiffness changes optic nerve patients multiple sclerosis ms without optic neuritis healthy adults via shear wave elastography swe methods seventy optic nerves thirtyfive patients ms sixty optic nerves thirty healthy subjects included prospectively study optic nerve optic disc od perineural area evaluated swe optic nerve sheat diameter onsd measured ultrasoundresults mean age patients 3968 999 years statistically significant difference groups terms onsd swe swe od swe perineural area levels p 005 ms group statistically significant difference found patients without optic neuritis mean age gender distribution duration ms types ms onsd swe swe od swe perineural area expanded disability status scale edss scores p 005 statistically significant difference terms onsd swe swe od swe perineural area ms patients without optic neuritis control group p 005 conclusion shear wave elastography measurements optic nerve optic disc perineural area contribute evaluation optic neuritis patient mspmid34392588 doi101111 ijcp14736,0.0
1 2 4trimethoxybenzene selectively inhibits nlrp3 inflammasome activation attenuates experimental autoimmune encephalomyelitis acta pharmacol sin 2021 feb 24 doi 101038 s41401021006138 online ahead printabstractnodlike receptor nlr family pyrin domaincontaining3 nlrp3 inflammasome implicated inflammationassociated diseases multiple sclerosis parkinsons disease stroke targeting nlrp3 inflammasome beneficial diseases nlrp3 inflammasomeselective inhibitors identified date essential oils eos liquid mixtures volatile low molecularweight organic compounds extracted aromatic plants show various pharmacological activities including antibacterial antifungal antiviral antioxidant antiinflammatory properties study screened active ingredients essential oils identified 1 2 4trimethoxybenzene 1 2 4ttb selective nlrp3 inflammasome inhibitor showed 1 2 4ttb 1 mm markedly suppressed nigericin atpinduced nlrp3 inflammasome activation thus decreased caspase1 activation il1 secretion immortalized murine bone marrowderived macrophages ibmdms primary mouse microglia moreover 1 2 4ttb specifically inhibited activation nlrp3 inflammasome without affecting absent melanoma 2 aim2 inflammasome activation demonstrated 1 2 4ttb inhibited oligomerization apoptosisassociated specklike protein containing card asc proteinprotein interaction nlrp3 asc thus blocking nlrp3 inflammasome assembly ibmdms primary mouse macrophages mice experimental autoimmune encephalomyelitis eae administration 1 2 4ttb 200 mg kg1 d1 ig 17 days significantly ameliorated eae progression demyelination conclusion results demonstrate 1 2 4ttb nlrp3 inflammasome inhibitor attenuates clinical symptom inflammation eae suggesting 1 2 4ttb potential candidate compound treating nlrp3 inflammasomedriven diseases multiple sclerosispmid33627802 doi101038 s41401021006138,1.0
outcomes laparoscopic oneanastomosis gastric bypass oagb patients morbid obesity multiple sclerosis obes surg 2021 jul 28 doi 101007 s11695021056242 online ahead printno abstractpmid34322840 doi101007 s11695021056242,0.0
scoping review breastfeeding women chronic diseases breastfeed med 2021 jul 28 doi 101089 bfm20210129 online ahead printabstractbackground approximately 1020 mothers chronic disease studies breastfeeding women chronic disease span multiple disciplines collated synthesize knowledge identify gaps objective review summarize published literature breastfeeding women chronic disease methods conducted scoping review original research systematic reviews identified medline embase cinahl 19902019 hand searching women chronic diseases reporting least one breastfeedingrelated topic conference abstracts casestudies studies pregnancyinduced conditions lactation pharmacology excluded content analysis narrative synthesis used analyze findings results identified 128 articles predominantly quantitative 805 conducted europe north america 656 analyzed sample sizes 200 570 published 2010 onward 688 diabetes 422 multiple sclerosis ms 195 epilepsy 133 common diseases studied breastfeeding primary focus approximately half 531 articles though definitions infrequently reported 328 moststudied topics breastfeeding duration exclusivity 557 reasons feeding behavior 191 knowledge attitudes breastfeeding 183 less studied topics 10 articles included milk expression behaviors breastfeeding difficulties feeding supports conclusions existing literature focuses primarily diabetes ms breastfeeding behaviors outcomes research examining broader range chronic diseases large sample sizes sufficient breastfeeding measurement detail can improve understanding breastfeeding disparities populationpmid34319788 doi101089 bfm20210129,0.0
risk outcomes covid19 patients multiple sclerosis eur j neurol 2021 jun 21 doi 101111 ene14990 online ahead printabstractbackground limited information available incidence outcomes covid19 patients multiple sclerosis ms study investigated risks sarscov2 infection covid19related outcomes patients ms compared general populationmethods regional registry created collect data incidence hospitalization rates intensive care unit icu admission death patients ms covid19 national government outcomes seroprevalence data used comparison study conducted 14 specialist ms treatment centers madrid spain february may 2020results twohundred nineteen patients included registry 51 hospitalized covid19 mean age standard deviation 453 124 years mean duration ms 119 89 years infection incidence rate lower patients ms general population adjusted incidence rate ratio 078 95 confidence interval 070080 hospitalization rates higher relative risk 503 376662 disease severity generally low one admission intensive care unit five deaths males ms higher incidence rates risk hospitalization females association found use diseasemodifying treatment hospitalization riskconclusion patients ms appear greater risks sarscov2 infection severe covid19 outcomes compared general population decision start continue diseasemodifying treatment based careful riskbenefit assessmentpmid34152073 doi101111 ene14990,0.0
cerebellum network disrupted static dynamic functional connectivity patterns cognitive impairment multiple sclerosis mult scler 2021 mar 81352458521999274 doi 101177 1352458521999274 online ahead printabstractbackground impact cerebellar damage dys function cognition remains understudied multiple sclerosisobjective assess cognitive relevance cerebellar structural damage functional connectivity fc relapsingremitting multiple sclerosis rrms secondary progressive multiple sclerosis spms methods study included 149 patients early rrms 81 late rrms 48 spms 82 controls cerebellar cortical imaging included fractional anisotropy grey matter volume restingstate functional magnetic resonance imaging mri cerebellar fc assessed literaturebased restingstate networks using static connectivity conventional correlations dynamic connectivity fluctuations fc strength measures compared groups related disability cognitionresults cognitive impairment ci cerebellar damage worst spms spms showed cerebellar connectivity changes compared early rrms controls lower static fc seen frontoparietal defaultmode networks higher dynamic fc seen dorsal ventral attention defaultmode deep grey matter networks cerebellar atrophy higher dynamic fc together explained 32 disability 24 cognitive variance higher dynamic fc related working verbal memory information processing speedconclusion cerebellar damage cerebellar connectivity changes prominent spms related worse cipmid33683158 doi101177 1352458521999274,0.0
role neurovascular conflict patients multiple sclerosis trigeminal neuralgia cephalalgia 2021 jul 133331024211027359 doi 101177 03331024211027359 online ahead printno abstractpmid34256652 doi101177 03331024211027359,0.0
toward remote assessment walking bout speed application patients multiple sclerosis ieee j biomed health inform 2021 apr 29 pp doi 101109 jbhi20213076707 online ahead printabstractgait speed powerful biomarker mobility mostly assessed controlled environments eg clinic wearable inertial sensors gait speed can estimated objective manner however previous works validated gait speed estimation algorithms clinical settings can different home assessments patients demonstrate actual performance moreover provide comfort users devising algorithm based single sensor setup essential end goal study develop validate new gait speed estimation method based machine learning approach predict gait speed clinical home assessments sensor lower back moreover two methods introduced detect walking bouts daily activities home validated algorithms 35 patients multiple sclerosis often presents mobility difficulties therefore robustness algorithm can shown impaired slow gait silver standard multisensor references achieved bias close zero precision 015 m s gait speed estimation furthermore proposed machine learningbased locomotion detection method median 968 specificity 930 sensitivity 964 accuracy 786 f1score detecting walking bouts home high performance proposed algorithm showed feasibility unsupervised mobility assessment introduced studypmid33914688 doi101109 jbhi20213076707,0.0
plasma neurofilament light chain levels predictors disease activity multiple sclerosis measured fourdomain neda status including brain volume loss mult scler 2021 feb 261352458521998039 doi 101177 1352458521998039 online ahead printabstractbackground research focused sensitive biomarkers multiple sclerosis ms objective aim study assess relationship plasma neurofilament light chain pnfl disease activity defined concept neda evident disease activity including brain volumetry cohort ms patients treated diseasemodifying treatment dmt methods levels pnfl single molecule array simoa technology examined 95 rrms relapsingremitting multiple sclerosis patients analyzed relationship neda3 status nedabvl brain volume loss neda3 extended brain volumetry last 12 months statistical model developed using logistic regression analysis including independent variables demographic clinical magnetic resonance imaging mri data dependent variables neda3 nedabvl statusresults mean age study participants n 95 62 females 3785 years standard deviation sd 962 median disability score 35 2541 receiver operating characteristics roc analysis showed pnfl predicts neda3 sensitivity specificity model 92 78 respectively p 0001 nedabvl status sensitivity specificity 80 65 respectively p 0001 conclusion results show pnfl levels useful biomarker disease activity determined nedabvl status including brain mrivolumetry patients rrmspmid33635154 doi101177 1352458521998039,0.0
teriflunomide provides protective properties oxygenglucosedeprivation hippocampal cerebellar slice cultures neural regen res 2021 nov 16 11 22432249 doi 104103 16735374310689abstractone major challenges emergency medicine outofhospital cardiac arrest ohca every year 5362 100 000 people worldwide suffer outofhospital cardiac arrest serious consequences whereas persistent brain injury major cause morbidity mortality surviving cardiac arrest today insufficient strategies known limit neurological damage ischemia reperfusion injury aim present study investigate whether teriflunomide approved drug treatment relapsingremittingmultiplesclerosis exerts protective effect brain cells vitro model ischemia therefore organotypic slice cultures rat hippocampus cerebellum exposed oxygenglucosedeprivation subsequently treated teriflunomide administration teriflunomide reperfusion time hippocampal cerebellar slice cultures significantly decreased amount detectable propidium iodide signal compared untreated culture indicating cells survive oxygenglucosedeprivation however hippocampal slice cultures showed higher vulnerability ischemic conditions sensitive response teriflunomide compared cerebellar slice cultures study suggests teriflunomide applied posttreatment oxygenglucosedeprivation protective effect hippocampal cerebellar cells organotypic slice cultures rats procedures conducted established standards german federal state north rhine westphalia accordance european communities council directive 2010 63 eu protection animals used scientific purposespmid33818508 doi104103 16735374310689,0.0
role integral type ii transmembrane protein bri2 health disease cell mol life sci 2021 sep 4 doi 101007 s00018021039325 online ahead printabstractbri2 type ii transmembrane protein ubiquitously expressed whose physiological function remains poorly understood although several recent important advances substantially impacted understanding bri2 biology function providing valuable information studies bri2 findings contributed better understanding bri2 biology underlying signaling pathways involved turn might provide novel insights respect neurodegeneration processes inherent bri2related pathologies namely familial british danish dementias alzheimers disease itm2brelated retinal dystrophy multiple sclerosis review provided stateoftheart outline bri2 biology physiological pathological conditions discuss proposed molecular underlying mechanisms overall bri2 knowledge reviewed extreme importance may contribute propose bri2 bri2 proteolytic fragments novel therapeutic targets neurodegenerative diseases alzheimers diseasepmid34480585 doi101007 s00018021039325,0.0
eosinophils dispensable development mog3555induced experimental autoimmune encephalomyelitis mice immunol lett 2021 sep 6s01652478 21 001425 doi 101016 jimlet202109001 online ahead printabstractexperimental autoimmune encephalomyelitis eae represents mouse model multiple sclerosis devastating neurological disorder eae development progression involves infiltration different immune cells brain spinal cord however less known potential role eosinophil granulocytes eae disease pathogenesis present study found enhanced eosinophil abundance accompanied increased concentration eosinophil chemoattractant eotaxin1 spinal cord course eae induced c57bl 6 mice immunization mog3555 peptide however absence eosinophils affect neuroinflammation demyelination clinical development severity eae assessed dblgata1 eosinophildeficient mice taken together despite enhanced abundance inflamed spinal cord disease progression eosinophils dispensable eae developmentpmid34499922 doi101016 jimlet202109001,1.0
polysaccharides confer benefits immune regulation multiple sclerosis interacting gut microbiota food res int 2021 nov 149110675 doi 101016 jfoodres2021110675 epub 2021 aug 28abstractpharmacological clinical studies consistently demonstrated polysaccharides exhibit great potential immune regulation polysaccharides can interact directly indirectly immune system triggering cellcell communication molecular recognition leading immunostimulatory responses gut microbiota adept foraging polysaccharides energy sources confers benefits context immunity chronic autoimmune disease multiple sclerosis compelling set interconnectedness gut microbiota natural polysaccharides immune regulation emerged review highlighted available avenues supporting existence interactions focus cytokinesmediated scfasmediated pathways additionally neuroimmune mechanisms gut microbiota communication brain multiple sclerosis also discussed will lay ground ameliorate multiple sclerosis via polysaccharide interventionpmid34600677 doi101016 jfoodres2021110675,0.0
pregnancy post autologous stem cell transplant beam conditioning multiple sclerosis mult scler 2021 apr 1913524585211005660 doi 101177 13524585211005660 online ahead printabstractbackground given increasing numbers multiple sclerosis ms patients undergoing autologous haematopoietic stem cell transplant ahsct worldwide women childbearing age overrepresented target population increasingly important review fertility pregnancy outcomes following ahsctobjective evaluate rate pregnancy complications postahsct msmethod retrospective evaluation rate pregnancy associated complications cohort patients postahsct beam conditioning ms since 2010 tertiary referral centreresults ongoing phase 2 trial ahsct ms 55 patients undergone ahsct 30 females childbearing age time transplantation four pregnancies occurred following ahsct two pregnancies carried term maternal neonatal complications reported either case two pregnancies carried term due elective terminations patients became pregnant unexpectedly 2 years following ahsct 21 male patients one patient fathered three children since ahsct newborn complicationsconclusions first report knowledge fertility outcomes sexes postahsct ms patients sexes counselled prior treatment infertility contraceptive usepmid33870788 doi101177 13524585211005660,0.0
nanosystems exosomes future approaches treating multiple sclerosis eur j neurosci 2021 sep 24 doi 101111 ejn15478 online ahead printabstractmultiple sclerosis ms immunemediated demyelinating disease central nervous system leads neurological dysfunctions severe disabilities ms pathology characterized damage bloodbrain barrier infiltration autoreactive t cells overactivate glial cells thereby initiating neuroinflammation accompanied formation demyelinating plaques neurodegeneration clinical deficits multifactorial disease depend progression myelin loss stage inflammation status axons activity oligodendrocyte precursor cells opcs despite significant progress treatment ms current therapies remain limited new approaches highly desirable nanosystems based liposomes nanoparticles among noteworthy therapeutic strategies investigated applications nanosystems alone drug carriers animal models ms found successfully alleviate symptoms disease exert antiinflammatory potential exosomes specific type nanosystem based nanometersized extracellular vesicles released different cells exhibit important healing features exosomes contain array antiinflammatory neuroprotective agents may contribute modulation immune system well promoting remyelination tissue repair review opportunities use nanosystems progression ms will discussed context cellspecific pathologies associated mspmid34561918 doi101111 ejn15478,1.0
fyn kinase activity role neurodegenerative disease pathology potential universal target mol neurobiol 2021 aug 25 doi 101007 s12035021025183 online ahead printabstractfyn nonreceptor tyrosine kinase belonging src family kinases sfks implicated several integral functions throughout central nervous system cns including myelination synaptic transmission recently fyn dysfunction associated pathological processes observed neurodegenerative diseases multiple sclerosis ms alzheimers disease ad parkinsons disease pd neurodegenerative diseases amongst leading cause death disability worldwide due ageing population prevalence predicted rise coming years symptoms across neurodegenerative diseases debilitating degenerative nature concerningly currently diseasemodifying therapies prevent progression important identify potential new therapeutic targets review will outline role fyn normal homeostatic processes well degenerative pathological mechanisms associated neurodegenerative diseases demyelination pathological protein aggregation neuroinflammation cognitive dysfunctionpmid34432266 doi101007 s12035021025183,1.0
correlation clinical disability t1 hypointense lesions#39 volume cerebral magnetic resonance imaging multiple sclerosis patients systematic review metaanalysis cns neurosci ther 2021 oct 3 doi 101111 cns13734 online ahead printabstractbackground evaluate correlation t1 hypointense lesions mean volume cerebral mri disability level patients multiple sclerosismethods included studies testing desired outcome adult patients diagnosed rrms spms feb 2021 searched pubmed embase central web science find relevant studies included studies assessed risk bias using tailored version quality prognosis studies quips tool extracted correlation coefficients converted fishers z scale metaanalysis using randomeffects model performed resultsresults included 27 studies 1919 participants metaanalysis revealed correlation coefficient 032 95 ci 026037 t1 hypointense lesions mean volume edss scorediscussion correlation t1 hypointense lesions mean volume edss interpreted low slightly moderate certainty evidence judged highpmid34605190 doi101111 cns13734,0.0
immunotherapy personalized treatment multiple sclerosis nervenarzt 2021 aug 24 doi 101007 s0011502101176z online ahead printabstractpersonalized medicine requires patientoriented approach exact classification disease determined underlying pathophysiological processes particular optimal treatment multiple sclerosis ms requires personalized treatment goes beyond pure concept precision medicine however due lack robust biomarkers beyond cranial magnetic resonance imaging lacking detailed understanding aspects ms pathogenesis approach yet fully implemented important questions better therapeutic stratification ms patients 1 ms start 2 spectrum ms really span multiple diseases 3 progressive phase disease begin 4 phase disease therapeutic window immunotherapy recent findings indicate ms represents spectrum diseases therapeutic delay several years optimal treatment effect diseasemodifying treatment depends personalized treatment ms important determine exact disease stage patient react development increase focal inflammatory activity timely mannerpmid34427718 doi101007 s0011502101176z,0.0
depression anxiety stress relative swallowing impairment persons multiple sclerosis dysphagia 2021 mar 30 doi 101007 s0045502010207x online ahead printabstractdysphagia symptoms depression anxiety stress common persons multiple sclerosis ms posited relationship dysphagia increased frequency psychological symptoms therefore aim present study examine associations symptoms psychological difficulties use emotional suppression cognitive reappraisal strategies dysphagia status persons ms one hundred persons ms prospectively assessed multiple domains functioning cognitive psychological dysphagiarelated participants underwent cognitive screening mini mental state examination completed two psychological inventories depression anxiety stress scale dass 21 emotion regulation questionnaire completed dysphagia multiple sclerosis questionnaire speechlanguage pathologist evaluated persons suspected dysphagia mann assessment swallowing ability dysphagia present 29 persons ms sample split accordingly two groups differed baseline respect expanded disability status scale scores significant betweengroup differences mental health symptoms use emotional regulation strategies accordingly multivariate logistic regressions showed increased symptoms psychological stress decreased use cognitive reappraisal strategies increased indicators emotional suppression independently predicted presence dysphagia clear pattern towards poorer psychological wellbeing persons dysphagia compared without psychological difficulties may contribute manifestation worsening dysphagia addressed treatment planning future investigations therapeutic interventions promote improvement mental state alongside swallowing function may highly beneficialpmid33783621 doi101007 s0045502010207x,0.0
cortical diffusion kurtosis imaging thalamic volume associated cognitive walking performance relapsingremitting multiple sclerosis j neurol 2021 apr 7 doi 101007 s00415021105434 online ahead printabstractbackground multiple sclerosis ms pronounced neurodegeneration manifests cerebral gray matter gm atrophy associated cognitive physical impairments microstructural changes gm estimated diffusion kurtosis imaging dki may reveal neurodegeneration undetectable conventional structural mri thus serve sensitive marker disease progressionobjective primary objective investigate relationships morphological diffusional properties cerebral gm physical cognitive performance relapsingremitting ms rrms patients secondary objective investigate relationship gm microstructure white matter wm injury estimated volume wm lesionsmethods sixtyseven rrms patients performed brief repeatable battery neuropsychological tests brbn 6minute walk test 6mwt six spot step test ssst underwent mri scans using structural dki protocols gm volumetrics dki measurements analyzed cortex deep gm structures using general linear model demographics physical cognitive performance covariatesresults mean diffusivity md cortex associated ssst 6mwt information processing global cognitive performance volume wm lesions addition thalamic volume associated ssst r2 021 6mwt r2 018 information processing r2 021 wm lesion volume r2 060 conclusion cortical diffusion thalamic volume associated walking cognitive performance rrms patients highly affected presence wm lesionspmid33829319 doi101007 s00415021105434,0.0
9 10anhydrodehydroartemisinin attenuates experimental autoimmune encephalomyelitis inhibiting th1 th17 cell differentiation inflammation 2021 mar 31 doi 101007 s10753021014565 online ahead printabstracthuman inflammatory disease multiple sclerosis ms demyelinating disease central nervous system cns experimental autoimmune encephalomyelitis eae commonly used experimental model key pathological features approximation ms interaction complex elements immune system cns determines ms pathogenesis however cure ms treatment ms still encounters great challenges thus finding effective diseasemodifying treatment imminent present study investigated whether 9 10anhydrodehydroartemisin adart compound derived artemisinin decrease demyelination eae underlying mechanisms established eae mice 100 mg kg 9 10anhydrodehydroartemisinin adart effectively reduced cns peripheral immune system infiltration inflammatory cells including cd4+ ifn+ th1 cells cd4+ il17a+ th17 cells correspondingly serum level ifn il17a also reduced vitro adart almost completely inhibited th17 differentiation partially inhibited th1 differentiation 10 m research revealed adart great promising avenue among current therapies mspmid33788130 doi101007 s10753021014565,1.0
hemophagocytic lymphohistiocytosis associated ocrelizumab treatment patient multiple sclerosis mult scler 2021 mar 51352458521993070 doi 101177 1352458521993070 online ahead printabstractbackground hemophagocytic lymphohistiocytosis hlh rarely recognized hyperinflammatory condition high death riskobjective objective describe case hlh patient multiple sclerosis ms treated ocrelizumabmethods clinical observation laboratory testing use hlh2004 criteria hlh diagnosisresults 32yearold caucasian female developed hlh ocrelizumab treatment met six eight hlh criteria including fever splenomegaly cytopenia hypertriglyceridemia hypofibrinogenemia high serum ferritin level low natural killer nk cellsconclusion hlh considered differential diagnosis ms patients displaying fever malaise syndrome following administration ocrelizumabpmid33666121 doi101177 1352458521993070,0.0
parvovirus b19 mumps virus antibodies major constituents intrathecal immune response european patients ms increase diagnostic sensitivity discriminatory power mrz reaction j neurol 2021 mar 26 doi 101007 s00415021104713 online ahead printabstractbackground positive mrz reaction defined intrathecal igg production least two constituents measles virus m rubella virus r varicella zoster virus z detectable 63 patients multiple sclerosis ms currently considered laboratory marker highest specificity positive likelihood ratio ms however m r z wellestablished constituents broader intrathecal humoral immune response msobjective identify additional antimicrobial antibodies inclusion classical mrz panel may result increased sensitivity without compromising markers high specificity msmethods determined antibody indices ais 11 viral bacterial agents m r z herpes simplex virus epsteinbarr virus mumps virus cytomegalovirus parvovirus b19 bordetella pertussis corynebacterium diphtheriae clostridium tetani paired cerebrospinal fluid serum samples patients ms disease controlsresults positive classical mrz reaction found 17 26 654 ms patients five frequently positive ais among patients ms m 769 z 615 r 577 parvovirus b19 423 mumps 28 addition parvovirus b19 mumps virus mrz panel resulted increase sensitivity ms group 654 731 22 initially mrznegative patients exhibiting de novopositive response extended mrz panel mrzplus distinguished sharply ms 3 ais 90 positives controls varying diagnoses migraine vasculitis 01 ais p 0000001 highest median ai ms group found parvovirus b19 397 followed measles virus 279 conclusion inclusion parvovirus b19 mumps virus test panel resulted increase sensitivity discriminatory power mrz results provide strong rational prospective studies investigating role extended mrz panels differential diagnosis mspmid33770235 doi101007 s00415021104713,0.0
activated microglia increase 18 kda translocator protein tspo expression multiple sclerosis brain glia 2021 jun 19 doi 101002 glia24052 online ahead printabstractto monitor innate immune responses cns 18 kda translocator protein tspo frequently used target pet imaging frequent assumption increased tspo expression human cns reflects proinflammatory activation microglia extrapolated rodent studies however tspo expression increase activated human microglia vitro studies multiple sclerosis ms lesions reveal tspo restricted proinflammatory microglia macrophages also present homeostatic reparative microglia investigated quantitative relationships tspo expression microglia macrophage phenotypes white matter lesions brains ms pathology white matter brains disease pathology normal appearing white matter nawm active ms lesions chronic active lesion rims 95 tspo+ cells microglia macrophages homeostatic microglial markers nawm control tissue lost reduced active lesions chronic active lesion rims reflecting cell activation nevertheless pixel analysis tspo+ cells n 12 225 revealed tspo expression per cell higher active lesions chronic active lesion rims myeloid cells activated relative nawm control data suggests whilst almost tspo signal active lesions chronic active lesion rims nawm control associated microglia macrophages tspo expression predominantly reflects cell density activation phenotype finding implications interpretation tspo pet signal ms cns diseases demonstrates limitation extrapolating tspo biology rodents humanspmid34145928 doi101002 glia24052,1.0
human papillomavirus lesions 16 ms patients treated fingolimod outcomes vaccination mult scler 2021 feb 251352458521991433 doi 101177 1352458521991433 online ahead printabstractfew cases human papillomavirus hpv diseases reported multiple sclerosis ms patients treated fingolimod describe case series 16 ms patients 11 women 5 men developing hpv lesions onset fingolimod without previous hpv history fingolimod discontinued six patients six patients received vaccination hpv good tolerance report highlights systematic hpv screening discussion hpv vaccination fingolimod onset crucial case occurrence hpv lesions fingolimod treatment comprehensive workup hpv disease necessary discussion hpv vaccination prevent secondary lesions prevalence studies hpv lesions needed ms patients different diseasemodifying therapiespmid33629615 doi101177 1352458521991433,0.0
effect dualtask training balance patients multiple sclerosis systematic review metaanalysis clin rehabil 2021 apr 202692155211010372 doi 101177 02692155211010372 online ahead printabstractobjective evaluate effects dualtask training static dynamic balance patients multiple sclerosisdata sources pubmed medline embase scopus pedro databases searched inception march 1 2021methods study conducted agreement preferred reporting items systematic reviews metaanalyses prisma guidelines two reviewers assessed studies inclusion extracted data used physiotherapy evidence database scale evaluate methodological quality riskofbias randomized clinical trial data pooled metaanalysis effect sizes 95 confidence interval ci calculated randomeffect models egger regression beggmazumdar rank correlation test used publication biasresults total 13 studies involving 584 patients 423 9 years mean sd 377 females met inclusion criteria systematic review nine included metaanalysis people received dualtask training interventions showed significant improvements timed go test 044 95 ci 022 065 pvalue0001 berg balance scale 046 95 ci 007 085 pvalue 002 low moderate heterogeneity studies found timed go test berg balance scale respectivelyconclusion findings current metaanalysis support dualtask training beneficial therapy improving dynamic balance functional mobility patients multiple sclerosis limited number studies investigated static balance performance dualtask training currently allow us draw conclusion possible improvements abilitypmid33874763 doi101177 02692155211010372,0.0
pharmacological interventions targeting nuclear factorkappa b signaling multiple sclerosis neural regen res 2021 oct 16 10 20232025 doi 104103 16735374308088no abstractpmid33642388 doi104103 16735374308088,0.0
primary central nervous system lymphoma essentials imaging findings brain nerve 2021 oct 73 10 10791086 doi 1011477 mf1416201897abstractprimary central nervous system lymphoma pcnsl consists 15 brain tumors lesions can identified using conventional techniques ct mri however differential diagnosis still challenging lesions show atypical findings similar diseases glioma infectious diseases progressive multifocal leukoencephalopathy toxoplasmosis demyelinating diseases multiple sclerosis review presented imaging findings conventional advanced neuroimaging techniques help differentiate pcnsl diseases detect characteristics prognostic factors treatment effects gene mutationspmid34615745 doi1011477 mf1416201897,1.0
effect spiritual counseling hope patients multiple sclerosis randomized clinical trial int j community based nurs midwifery 2021 oct 9 4 313324 doi 1030476 ijcbnm2021886051523abstractbackground spiritual practices recently emerged beneficial mental physical health present study conducted determine effect spiritual counseling hope among patients multiple sclerosis ms methods single blind randomized controlled clinical trial conducted patients ms apriljune 2020 kashan iran 50 patients randomly assigned two 25member groups patients intervention group participated eight 60minute spiritual counseling program asked fill demographic information questionnaire intervention herth hope index hhi immediately 4th week study month intervention 8th week study data analyzed using chisquare independent samples ttest repeated measures anova spss version 16 significance level considered p005results results showed differences two groups intervention statistically significant terms demographic variables p005 mean score hope p061 however total mean score hhi intervention group significantly different control group immediately month intervention 4495142 vs 3166245 4325184 vs 3058224 respectively p0001 according results repeated measures anova level hope dimensions significantly changed intervention group time p0001 conclusion results present study showed spiritual counseling promoted hope score patients ms recommended spiritual counseling use complementary therapy along counseling treatments increase hope patients mstrial registration number irct20190819044567npmid34604400 pmcpmc8479289 doi1030476 ijcbnm2021886051523,0.0
optical coherence tomography monitoring diagnosing retinal changes multiple sclerosis brain behav 2021 sep 14e32302 doi 101002 brb32302 online ahead printabstractthis study explores use optical coherence tomography oct monitor diagnose multiple sclerosis ms analysis reduced total macular volume peripapillary retinal nerve fiber layer thinning shown severity defects increases ms progresses reflecting progressive degeneration nerve fibers retinal ganglion cells oct parameters noninvasive sensitive indicators can used assess progression neurodegeneration inflammation mspmid34520634 doi101002 brb32302,0.0
spastic paresis arms flaccid paralysis legs secondary progressive multiple sclerosis nervenarzt 2021 mar 12 doi 101007 s00115021011032 online ahead printno abstractpmid33709169 doi101007 s00115021011032,0.0
mindfulnessand acceptancebased interventions symptom reduction people multiple sclerosis systematic review metaanalysis arch phys med rehabil 2021 apr 1s00039993 21 002604 doi 101016 japmr202103011 online ahead printabstractobjective examine effects mindfulness acceptancebased interventions mabis reducing symptoms people multiple sclerosis ms data sources comprehensive search conducted within pubmed cinahl psycinfo scopus databases articles published inception july 3 2020study selection randomized controlled trials rcts included mabis provided people ms exclusively reported preand posttest results symptoms depression anxiety stress fatigue pain among people msdata extraction characteristics included rcts data metaanalysis extracted quality included rcts assessed using cochrane collaboration risk bias tooldata analysis random effects model inverse variance method used effect size reported standardized mean difference heterogeneity assessed using i2 statisticresults 23 rcts met eligibility criteria metaanalyses found large effects mabis reducing depressive symptoms anxiety stress pain moderate effect mabis reducing fatigue immediate posttest large effects mabis reducing depressive symptoms anxiety stress followup also found moderate effect reducing fatigue found followup significant effect mabis reducing pain followupconclusions relatively fewer studies included metaanalyses pain immediate posttest followup stress fatigue followup overall risk bias unclear future highquality studies followup evaluations needed support effects mabis reducing symptoms people ms examine intervention features increase maintain effectspmid33812883 doi101016 japmr202103011,0.0
analysis plateletderived growth factor receptor oligodendrocyte transcription factor 2 markers following hydroxychloroquine administration animal induced multiple sclerosis model metab brain dis 2021 aug 3 doi 101007 s11011021008028 online ahead printabstractit shown following demyelination oligodendrocyte progenitor cells opcs migrate lesion site begin proliferate differentiate study aimed investigate effects hydroxychloroquine hcq expression olig2 pdgfr markers myelination process c57bl 6 mice fed cuprizone pellets 5 weeks induce demyelination return normal diet 1 week stimulate remyelination phase animals except cpz vehicle groups exposed hcq 25 10 100 mg kg via drinking water end study animals euthanized perfused brain samples assessed myelination immunohistochemistry evaluation remarkable high rate olig2 + cells groups treated 10 100 mg kg hcq demyelination phase decreasing trend remyelination phase however significant difference groups phase phase ii based percentage olig2+ total cells corpus callosum region number pdgfr+ cells group treated 10 mg kg hcq significant first phase p value 005 considering 100 mg kg hcq group highest level pdgfr well highest level myelin repair lfb staining inferred effective dose inducing proliferation migration opcspmid34342813 doi101007 s11011021008028,1.0
evaluating contributions dermatologists management systemic sclerosis retrospective analysis j eur acad dermatol venereol 2021 apr 18 doi 101111 jdv17288 online ahead printabstractsystemic sclerosis ssc autoimmune condition characterized cutaneous sclerosis potential internal organ involvement1 given multisystem nature ssc multiple disciplines often involved management however skin affected 90 patients 2 dermatologists variably involved management ssc potentially first evaluating patients late disease course times allpmid33866612 doi101111 jdv17288,0.0
evaluation pharmacokinetics safety drugdrug interactions oral suspension edaravone healthy adults clin pharmacol drug dev 2021 mar 11 doi 101002 cpdd925 online ahead printabstractintravenous iv edaravone approved amyotrophic lateral sclerosis als treatment iv administration places burden patients development orally administered als treatments needed therefore 2 phase 1 studies oral formulations edaravone healthy subjects examined pharmacokinetics pk safety racial differences drugdrug interactions ddis investigated dose oral formulation considered bioequivalent approved dose iv formulation study 1 placebocontrolled randomized singleblind study singleascendingdose oral edaravone dose range 30 300 mg n 56 study 2 conducted 2 cohorts n 84 first assessed ddis multipledose edaravone 120 mg day given 5 8 days coadministered singledose rosuvastatin sildenafil furosemide second evaluated pk racial japanese white differences pk parameters doses 100mg edaravone oral formulation edaravone well absorbed plasma concentrations unchanged edaravone increased dose proportionally within dose range 30 300 mg effect race oral edaravone pk notable ddi effects possibly caused orally administered edaravone observed oral edaravone formulations safe tolerable assessed conditions mathematical modeling determined equivalent exposures plasma approved dose iv edaravone formulation reported previously achieved oral edaravone formulation administered dose 100 mg absolute bioavailability 60pmid33704925 doi101002 cpdd925,0.0
dietary nutrition neurological disease therapy current status future directions pharmacol ther 2021 apr 23107861 doi 101016 jpharmthera2021107861 online ahead printabstractadequate food intake relative abundance dietary nutrients undisputed effects brain function now substantial evidence dietary nutrition aids prevention remediation neurologic symptoms diverse pathological conditions newly described influences dietary factors alterations mitochondrial dysfunction epigenetic modification neuroinflammation important mechanisms responsible action nutrients brain health review discuss state evidence supporting distinct dietary interventions including dietary supplement dietary restriction ability tackle neurological disorders using alzheimers disease parkinsons disease stroke epilepsy traumatic brain injury amyotrophic lateral sclerosis huntingtons disease multiple sclerosis examples additionally also highlighting diverse potential mechanisms metabolic control epigenetic modification neuroinflammation gutbrain axis utmost importance nutrient supply risk neurologic condition therapeutic response finally also highlight novel concept dietary nutrient intervention reshapes metabolismepigeneticsimmunity cycle remediate brain dysfunction targeting metabolismepigeneticsimmunity network will delineate new blueprint combating neurological weaknessespmid33901506 doi101016 jpharmthera2021107861,0.0
epigallocatechin3 gallate regulates macrophage subtypes immunometabolism ameliorate experimental autoimmune encephalomyelitis cell immunol 2021 aug 6 368104421 doi 101016 jcellimm2021104421 online ahead printabstractepigallocatechin3 gallate egcg polyphenolic component tea potential curative effects patients autoimmune diseases multiple sclerosis ms autoimmune disease affecting central nervous system cns remains unknown whether egcg can regulate macrophage subtypes ms evaluated effects egcg experimental autoimmune encephalomyelitis eae ms mouse model found egcg treatment reduced eae severity macrophage inflammation cns moreover eae severity well correlated ratio m1 m2 macrophages egcg treatment suppressed m1 macrophagemediated inflammation spleen vitro experiments showed egcg inhibited m1 macrophage polarization promoted m2 macrophage polarization effects likely related inhibition nuclear factorb signaling glycolysis macrophages egcg macrophages overall findings provided important insights mechanisms egcg may mediate mspmid34385001 doi101016 jcellimm2021104421,0.0
air pollution multiple sclerosis comprehensive review neurol sci 2021 aug 3 doi 101007 s10072021055084 online ahead printabstractmultiple sclerosis ms inflammatory autoimmune demyelinating disorder central nervous system cns leading progressive functional impairments many intrinsic acquired factors believed associated development relapse terms environmental factors air pollution gained much attention recent decades chronic exposure ambient air pollution seems increase level proinflammatory markers human brain can lead neuroinflammation neurodegeneration bloodbrain barrier bbb breakdown events may also associated risk ms development relapse review aimed summarize recent findings around impact air pollutants including particulate matter pm10 pm25 ultrafine particles gaseous pollutants carbon monoxide co nitrogen oxides nox sulfur dioxide so2 ozone o3 heavy metals ms development relapsepmid34341860 doi101007 s10072021055084,1.0
benefits safe sunlight exposure vitamin d beyond j steroid biochem mol biol 2021 jul 27105957 doi 101016 jjsbmb2021105957 online ahead printabstractthis review examines beneficial effects ultraviolet radiation systemic autoimmune diseases including multiple sclerosis type diabetes epidemiological evidence vitamin dindependent effects sunlight apparent ultraviolet radiation addition role synthesis vitamin d stimulates antiinflammatory pathways alters composition dendritic cells t cells t regulatory cells induces nitric oxide synthase heme oxygenase metabolic pathways may directly indirectly mitigate disease progression susceptibility recent work also explored immunemodulating functions ultraviolet radiation affect type ii diabetes cancer current global pandemic caused sarscov2 diseases particularly important amidst global changes lifestyle result unhealthy eating increased sedentary habits alcohol tobacco consumption compelling epidemiological data shows increased ultraviolet radiation associated reduced rates certain cancers colorectal cancer breast cancer nonhodgkins lymphoma ultraviolet radiation exposure correlated susceptibility mortality rates covid19 thus understanding effects ultraviolet radiation vitamin ddependent independent pathway necessary understand influence course many human diseasespmid34329737 doi101016 jjsbmb2021105957,0.0
sepsis multiple sclerosis causative links outcomes immunol lett 2021 jul 25s01652478 21 001176 doi 101016 jimlet202107008 online ahead printabstractsepsis lifethreatening condition characterized acute cytokine storm followed prolonged dysfunction immune system survivors postseptic lymphopenia functional deficits remaining immune cells lead increased susceptibility secondary infections morbid conditions causing late death patients state postseptic immunoparalysis may also influence disorders stemming inappropriate overactive immune responses autoimmune immunoinflammatory diseases including multiple sclerosis addition ongoing autoimmunity likely influences susceptibility outcome sepsis review article addresses bidirectional relationship sepsis multiple sclerosis focus immunologic mechanisms interaction potential directions future studiespmid34320384 doi101016 jimlet202107008,0.0
role myeloidderived suppressor cell mdsc autoimmunity potential therapeutic target inflammopharmacology 2021 jul 20 doi 101007 s10787021008463 online ahead printabstractmyeloid suppressor cells mdscs important class immuneregulating cells can suppress t cell function knowledge function mdsc comes studies cancer models recent studies however greatly contributed description mdsc involvement autoimmune diseases known cell population may negatively affect immune responses regulating function cd4+ cd8+ cells makes attractive target autoimmune diseases therapy however many questions mdsc activation differentiation inhibitory functions remain unanswered study summarized role mdscs various autoimmune diseases potential targeting therapeutic benefits discussedpmid34283371 doi101007 s10787021008463,0.0
ifnalpha key therapeutic target multiple autoimmune rheumatic diseases drug discov today 2021 jul 2s13596446 21 00283x doi 101016 jdrudis202106010 online ahead printabstractinterferon ifn emerged major therapeutic target several autoimmune rheumatic diseases review focus clinical preclinical advances antiifn treatments systemic lupus erythematosus sle primary sjgren syndrome pss systemic sclerosis ssc dermatomyositis dm high medical need persists promising achievements obtained following direct ifn neutralization targeting production cytosolic nucleic acid sensor pathways blocking downstream effects type ifn receptor focus molecular profiling data integration approaches crucial steps select patients likely benefit antiifn therapies within precision medicine approachpmid34224903 doi101016 jdrudis202106010,0.0
burden neurological comorbidities six autoimmune bullous diseases populationbased study j eur acad dermatol venereol 2021 jun 21 doi 101111 jdv17465 online ahead printabstractbackground apart bullous pemphigoid bp association autoimmune bullous diseases aibds neurological conditions poorly understoodobjective estimate association wide array aibds neurological conditionsmethods retrospective crosssectional study recruited patients bp mucous membrane pemphigoid mmp epidermolysis bullosa acquisita eba pemphigoid gestationis pg pemphigus vulgaris pv pemphigus foliaceus pf patients compared age sexmatched control subjects regard lifetime prevalence parkinsons disease pd alzheimers disease ad stroke epilepsy multiple sclerosis ms logistic regression used calculate specified neurological disorders results current study included 1 743 251 106 126 860 103 patients diagnosed bp mmp eba pg pv pf respectively patients compared 10 141 1 386 606 933 5 142 588 matched controls respectively investigated neurological conditions pd associated bp 271 95 ci 219335 ad bp 211 95 ci 173257 mmp 237 95 ci 103547 eba 600 95 ci 1901897 pv 224 95 ci 140360 stroke bp 184 95 ci 155219 eba 279 95 ci 111701 epilepsy bp 218 95 ci 172277 pv 180 95 ci 119273 ms significantly cluster six aibdsconclusion addition bp eba pv found cluster neurological comorbidities patients aibds compatible symptoms may carefully assessed comorbid neurological disorderspmid34153122 doi101111 jdv17465,0.0
evaluation matrix metalloproteinase9 plasma levels untreated new relapsingremitting multiple sclerosis patients firstdegree family metab brain dis 2021 jun 11 doi 101007 s11011021007589 online ahead printabstractmatrix metalloproteinase especially matrix metalloproteinase9 mmp9 vital roles disruption blood barrier neuroinflammation pathogenesis multiple sclerosis ms patients goal study estimate plasma levels mmp9 firstdegree family ms patients 35 untreated patients definite rrms relapsingremitting multiple sclerosis according mcdonald criteria 24 healthy controls hc 26 highrisk families untreated rrms patients enrolled study plasma levels mmp9 analyzed elisa enzymelinked immunosorbent assay although plasma protein levels mmp9 elevated significantly untreated rrms group p 005 p 00203 compared control group family ms patients significance p 0208 mean plasma mmp9 concentration hc untreated rrms highrisk group 322268 pg ml 611926 pg ml 518939 pg ml respectively mmp9 used understand role biomarker pathogenesis ms highrisk group found plasma levels mmp9 new cases ms increased considerably confirming importance mmp9 predictive marker highrisk group will needed researchespmid34115275 doi101007 s11011021007589,0.0
unstable ataxic hand alajouanine akerman distinct contribution rev neurol paris 2021 jun 21s00353787 21 00552x doi 101016 jneurol202012004 online ahead printabstractwe discuss historical perspective whether 1931 description unstable ataxic hand thophile alajouanine fifth successor charcot la salptrire brazilian neurologist abraham akerman studying france merits considered distinct contribution visvis earlier description oppenheim useless hand syndrome specific object article alajouanine akerman semiologic sign namely pseudoathetosis localized hand original description oppenheim symptomcomplex came known useless hand syndrome include abnormal movement moreover result useless hand syndrome originating clinical classification multiple sclerosis based localization lesions involves topographic etiologic diagnoses specificities contrast unstable ataxic hand can observed useless hand syndrome syndromes involving predominantly sensory symptoms numb clumsy hands due high cervical spondylosis extramedullary tumor cortical sensory syndrome commonly due parietal stroke thoroughly described context symptomcomplex alajouanine akermans unstable ataxic hand merits considered distinct valuable contributionpmid34167805 doi101016 jneurol202012004,0.0
gad65 autoimmunity treatment nivolumab multifocal presentation neurol sci 2021 may 11 doi 101007 s10072021053120 online ahead printabstractintroduction neurological disorders considered rare complications immunecheckpoint inhibitorcase description report 63yearold man recurrence melanoma presented epilepsy limbic encephalitis cerebellar ataxia stiff person syndrome soon treatment nivolumab immunecheckpoint inhibitor autoimmune screening serum csf gad65 detected significant response steroids intravenous immunoglobulins observed cancer recurred nivolumab discontinuation parallel epileptic seizure worsening cognitive impairment patient dieddiscussion case expands spectrum gad65associated conditions induced immunecheckpoint inhibitor underlines treatment complexity neurological complications tumour recurrence occurpmid33977307 doi101007 s10072021053120,0.0
nasogastric tube insertion intubated patients guide wire rope prospective randomized controlled study int j clin pract 2021 jun 12e14508 doi 101111 ijcp14508 online ahead printabstractintroduction nasogastric tube ngt insertion sometimes required intubated patients ngts prone kink coil blind insertion hypothesized wire rope guideassisted ngt insertion chin lift can significantly improve firstattempt success rate conventional technique insertion intubated patientsobjective mean time successful insertion ngt failure rate ngt insertion first attempt failure rate ngt insertion second attempt overall failure rate assessed along incidence complicationsmethod prospective clinical trial conducted one hundred adult patients presenting abdominal surgery general anesthesia patients randomized experimental technique wire rope guide chin lift wire group control technique head flexion control group insertion ngtresults firstattempt success rate 98 wire group compared 74 control group p 0001 thus firstattempt failure rate 2 wire group compared 26 control group p 0001 median time required insert ngt significantly shorter wire group 35348 vs 61562 seconds p 0001 incidences kinking coiling bleeding moderate injuries significantly lower wire groupconclusion use rope wire guide correct positioning ngt intubated patients less timeconsuming high firstattempt success rate lower incidence procedurerelated injuries compared conventional methodpmid34118103 doi101111 ijcp14508,0.0
guidance decision coaching patient decision aids scoping reviews inform international patient decision aid standards ipdas med decis making 2021 mar 24272989x21997330 doi 101177 0272989x21997330 online ahead printabstractintroduction 2005 international patient decision aid standards ipdas collaboration identified guidance decision coaching important dimensions patient decision aids ptdas developed set quality criteria sought update definitions theoretical rationale evidence guidance decision coaching used within alongside ptdas ipdas update 20methods conducted 2 scoping reviews guidance decision coaching including systematic searches hand search cochrane review ptdas eligible studies randomized controlled trials rcts guidance decision coaching used alongside ptdas data including conceptual models summarized narratively metaanalyses appropriateresults 1022 citations found rcts evaluated guidance ptdas 2013 definition guidance endorsed made minimal changes description guidance 3039 citations identified 21 rcts decision coaching informed 5 conceptual models stating people exposed decision coaching likely progress making informed decisions consistent values compared usual care decision coaching ptdas led improved knowledge mean difference md 195 100 95 confidence interval ci 100290 5 rcts compared decision coaching alone ptdas led small improvement knowledge md 36 100 95 ci 1063 3 rcts variable effects outcomes simplified decision coaching definition slightly defined minimal decision coaching elementsconclusion found evidence propose changes guidance ipdas decision coaching continuing used alongside ptdas inadequate evidence added effectiveness compared ptdas alone decision coaching definition updated minimal elementspmid33759626 doi101177 0272989x21997330,0.0
exercise behavioural interventions show promise treating fatigue multiple sclerosis network metaanalysis mult scler 2021 apr 201352458521996002 doi 101177 1352458521996002 online ahead printabstractbackground fatigue common debilitating symptom multiple sclerosis ms without current standardised treatmentobjective aim systematic review network metaanalyses estimate relative effectiveness fatiguetargeted nontargeted exercise behavioural combined behavioural exercise interventionsmethods nine electronic databases august 2018 searched 113 trials n 6909 included 34 fatiguetargeted 79 nonfatiguetargeted trials intervention characteristics extracted using template intervention description replication guidelines certainty evidence assessed using graderesults pairwise metaanalyses showed exercise interventions demonstrated moderate large effects across subtypes regardless treatment target largest effect balance exercise smd 084 cognitive behavioural therapies cbts showed moderate large effects smd 060 fatiguetargeted treatments showing larger effects targeting distress network metaanalysis showed balance exercise performed significantly better compared exercise behavioural intervention subtypes except cbt cbt estimated superior energy conservation behavioural interventions combined exercise also moderate large effectconclusion treatment recommendations balance combined exercise tentative certainty evidence moderate certainty evidence cbt highpmid33876986 doi101177 1352458521996002,0.0
longterm analysis patients benign multiple sclerosis new insights disability course j neurol 2021 mar 31 doi 101007 s00415021105010 online ahead printabstractobjective describe course disability patients benign multiple sclerosisie expanded disability status scale score 3 10 years disease onsetfor 30 years disease onset evaluated proportion patients remaining benign state long term factor associated favorable outcome determined pattern disability course loss benign statusmethods patients selected relsep french populationbased registry studied probability kaplanmeier method predictors multivariate cox model remaining 3 year 10 course disability score 3 according duration benign phase patients 30 years followup graphs course mean expanded disability status scale scores subgroups patients results 2295 3440 patients benign multiple sclerosis 667 probability remaining benign year 30 026 95 ci 026032 young age disease onset good recovery first relapse associated remaining benign graphs illustrate lost benign status years 10 30 follow twostage course beyond score 3 disability accumulation similar lower disability scores advanced age associated longer benign periodsconclusion longer patient remains benign state lower final edss advanced agepmid33791847 doi101007 s00415021105010,0.0
early recognition chronic rejection face allotransplant patient alopecia j cutan pathol 2021 jun 3 doi 101111 cup14069 online ahead printabstractthe features chronic rejection cr fullface vascularized composite allotransplantation vca wellknown herein report fullface transplant patient experienced 2 episodes acute rejection ar 3 episodes ar cr course 6years patient noticed small round patch hair loss beard 9 months second ar episode occurred 21 months posttransplantation biopsy alopecic patch showed lichen planopilarislike features suggestive early cr despite increase immunosuppressive dosages alopecia progressed following second third ar cr episodes alopecia became pronounced addition hyperpigmentation well sclerosis telangiectasia findings multiple biopsies showed cr based findings think alopecia lichen planopilarislike histopathological features similar grade iii ar features particularly hair follicles appears early finding cr presented patient findings indicate follicular involvement may significant feature cr vca patients can present prior sclerosis vasculopathy loss adnexa present case uniquely important due distinctive presentation cr hair follicles clinically histopathologically affected leading progressive irreversible alopecia lichen planopilarislike histopathologypmid34085296 doi101111 cup14069,0.0
biopsychosocial factors explain selfmanagement behaviors multiple sclerosis role demographics cognition personality psychosocial physical functioning arch phys med rehabil 2021 jun 24s00039993 21 00455x doi 101016 japmr202105012 online ahead printabstractobjectives examine biopsychosocial correlates overall individual selfmanagement behaviors persons multiple sclerosis pwms including demographics cooccurring medical diagnoses cognition personality traits psychosocial physical functioning variablesdesign prospective crosssectional cohort studysetting communitybased comprehensive ms centerparticipants adults ms n 112 completed brief neuropsychological battery included selfreport survey performancebased measures cognitive functioninterventions applicablemain outcome measures ms selfmanagement scalerevised total score primary outcome five subscales healthcare provider relationship communication treatment adherence barriers social family support ms knowledge information health maintenance behaviors secondary outcomesresults dmt usage 039 social support 031 subjective prospective memory 025 emotional wellbeing 020 histories diabetes 018 high cholesterol 015 significantly associated overall selfmanagement multivariable model correlates individual selfmanagement behaviors also describedconclusions findings provide insights biopsychosocial characteristics contributing pwms overall individual selfmanagement behaviors next steps will evaluate factors clinical interventionpmid34175273 doi101016 japmr202105012,0.0
diseasemodifying treatment secondary progressive multiple sclerosis nervenarzt 2021 mar 3 doi 101007 s00115021010806 online ahead printabstractbackground multiple sclerosis ms disease continuum clinically isolated syndrome relapsing remitting ms secondary progressive ms spms numerous therapeutic approaches proven efficacy relapse focal inflammatory disease aspects whereas treatment secondary progression associated neuropathological aspects continues challengeobjective overview current options diseasemodifying treatment spmsmaterial methods results randomized clinical trials presented evaluated substancespecific basisresults randomized spms trials showed inconsistent results regarding disability progression beta interferons negative results natalizumab oral cladribine ocrelizumab reduced disability progression relapsing ms specifically studied spms population positive results mitoxantrone partially applicable current spms patients siponimod substance crosses bloodbrain barrier expand trial demonstrated significant reduction risk disability progression typical spms subgroup analyses suggest higher efficacy siponimod younger patients active spmsconclusion limited evidence use previously available diseasemodifying treatment spms siponimod represents new therapeutic option active spms defined relapses focal inflammatory mri activity establish therapeutic indications siponimod early detection relapseindependent progression well differentiation active spms inactive disease critical importancepmid33656569 doi101007 s00115021010806,0.0
valproic acid suppresses cuprizoneinduced hippocampal demyelination anxietylike behavior promoting cholesterol biosynthesis neurobiol dis 2021 aug 27105489 doi 101016 jnbd2021105489 online ahead printabstractmyelin consists several layers tightly compacted membranes form insulating sheath around axons membranes highly enriched cholesterol essential myelination process proper myelination crucial various neurophysiological functions demyelination may cause cns disease multiple sclerosis ms recent studies demonstrated demyelination occurs white matter also grey matter hippocampus may cause cognitive deficits mental disorders valproic acid vpa anticonvulsant agent prescribed treatment epilepsy seizure recently vpa reported alter cholesterol metabolism neural cells suggesting may play important role myelin biogenesis study found significant demyelination hippocampus mouse cuprizone model accompanied reduced cholesterol biosynthesis increased anxietylike behavior vpa treatment however suppressed cuprizoneinduced hippocampal demyelination anxietylike behavior promoting cholesterol biosynthesis data identify important role vpa hippocampal demyelination process hippocampal demyelinationrelated behavior deficit via regulation cholesterol biosynthesis provides new insights mechanisms vpa protective agent cns demyelinationpmid34461265 doi101016 jnbd2021105489,1.0
hyperprolactinemia galactorrhea duloxetine neuropathic pain management agri 2021 oct 33 4 268271 doi 1014744 agri201908769abstractduloxetine serotoninnorepinephrine reuptake inhibitor widely used chronic pain treatment various diseases hyperprolactinemia galactorrhea rare side effects medication reported 34yearold female multiple sclerosis used duloxetine pain management mood disorder experienced galactorrheapmid34671951 doi1014744 agri201908769,0.0
perceived social support mental health marital satisfaction multiple sclerosis patients perspect psychiatr care 2021 mar 17 doi 101111 ppc12760 online ahead printabstractpurpose study aimed examine patients perceived social support mental health marital satisfactiondesign methods data collected via patient information form barthel index activities daily living marital life scale multidimensional scale perceived social support general health questionnaire 72 patientsfindings multiple sclerosis ms patients moderate level marital satisfaction perceived social support showed positive correlation marital satisfaction negative correlation mental health disorders mspractice implications results will facilitate perception mental problems marital satisfaction social support ms patients nursespmid33728706 doi101111 ppc12760,0.0
retinal optical coherence tomography magnetic resonance imaging neuromyelitis optica spectrum disorders mogantibody associated disorders updated review expert rev neurother 2021 sep 23 doi 101080 1473717520211982697 online ahead printabstractintroduction neuromyelitis optica spectrum disorders nmosd myelin oligodendrocyte glycoprotein igg antibody associated disorders mogad comprise two groups rare neuroinflammatory diseases cause attackrelated damage central nervous system cns clinical attacks often characterized optic neuritis transverse myelitis lesser extent brainstem encephalitis area postrema syndrome retinal optical coherence tomography oct noninvasive technique allows vivo thickness quantification retinal layers apart oct magnetic resonance imaging mri plays increasingly important role nmosd mogad diagnosis based current international diagnostic criteria retinal oct brain spinal cord optic nerve mri can help distinguish nmosd mogad neuroinflammatory diseases particularly multiple sclerosis monitor diseaseassociated cnsdamageareas covered article summarizes current status imaging research nmosd mogad reviews clinical relevance oct mri relevant imaging techniques differential diagnosis screening monitoring disease courseexpert opinion retinal oct mri can visualize quantify cns damage vivo improving understanding nmosd mogad pathology disease mechanisms efforts standardization imaging techniques essential implementation clinical practice outcome parameters clinical trialspmid34551653 doi101080 1473717520211982697,1.0
updated review teriflunomide#39 s use multiple sclerosis neurodegener dis manag 2021 sep 6 doi 102217 nmt20210014 online ahead printabstractteriflunomide daily oral diseasemodifying therapy demonstrated consistent efficacy safety tolerability patients relapsing forms multiple sclerosis ms first clinical episode suggestive ms treated 12 years review update previous version examined data teriflunomide core clinical development program extension studies data since become available active comparator trials diseasemodifying therapies treatmentrelated changes brain volume analyzed using structural image evaluation using normalization atrophy realworld evidence including patientreported outcomes initial data potential antiviral effects teriflunomide patients ms including case reports patients infected 2019 novel coronavirus sarscov2 also presentedpmid34486382 doi102217 nmt20210014,0.0
costeffectiveness medicinal cannabis management refractory symptoms associated chronic conditions systematic review economic evaluations value health 2021 oct 24 10 15201530 doi 101016 jjval2021041276 epub 2021 jul 17abstractobjectives although growing body evidence suggesting cannabinoids may relieve symptoms illnesses relatively highcost therapies compared illicit growth supply article aimed comprehensively review economic evaluations medicinal cannabis alleviating refractory symptoms associated chronic conditionsmethods seven electronic databases searched articles published september 6 2020 quality reporting economic evaluations assessed using consolidated health economic evaluation reporting standards checklist extracted data grouped subcategories according types medical conditions organized tables reported narrativelyresults review identified 12 costutility analyses conducted across variety diseases including multiple sclerosis ms n 8 pediatric drugresistant epilepsies n 2 chronic pain n 2 incremental costeffectiveness ratio varied widely cost saving us451 800 per qualityadjusted lifeyear depending setting perspectives types medicinal cannabis indications nabiximols costeffective intervention ms spasticity multiple european settings cannabidiol found costeffective dravet syndrome canadian setting whereas costutility analysis conducted us setting deemed cannabidiol costeffective lennoxgastaut syndrome overall study quality good publications meeting 70 100 median 83 consolidated health economic evaluation reporting standards checklist criteriaconclusions medicinal cannabisbased products may costeffective treatment options ms spasticity dravet syndrome neuropathic pain although literature nascent welldesigned clinical trials health economic evaluations needed generate adequate clinical costeffectiveness evidence assist resource allocationpmid34593176 doi101016 jjval2021041276,0.0
association dietary total antioxidant capacity nmoigg seropositivity patients neuromyelitis optica spectrum disorder clin neurol neurosurg 2021 aug 21 209106903 doi 101016 jclineuro2021106903 online ahead printabstractobjectives growing evidence highlighting role environmental risk factors nmoigg seropositivity patients neuromyelitis optica spectrum disorder nmosd present study investigated possible association dietary total antioxidant capacity tac nmoigg seropositivity nmosd patientsmethods fiftysix patients definite diagnosis nmosd included study data patients age gender height weight cigarette smoking status alcohol consumption collected recorded body mass index bmi also calculated addition dietary habits patients evaluated using adjusted semiquantitative food frequency questionnaire ffq consists 168 food items dietary tac calculated using oxygen radical absorption capacity orac method enzymelinked immunosorbent assay elisa method used determine nmoigg serum status association dietary tac odds nmoigg seropositivity measured using logistic regression analysisresults mean dietary tac 83628 molte 1000 kcal seronegative patients 66099 molte 1000 kcal seropositive patients significant difference mentioned groups patients p 002 inverse association found dietary tac odds nmoigg seropositivity three regression models higher dietary intake antioxidant resulted significant findings follows 92 95 ci 001053 97 95 ci 000034 97 95 ci 000032 lower odds nmoigg seropositivity fourth quartiles first second third regression model respectively moreover inverse association fruit intake odds nmoigg seropositivity significant third quartile or010 95ci 001097 conclusion present study indicated significant inverse association dietary tac nmoigg seropositivity nmosd patients definite treatment can offered nmosd nutrition modifiable factor regard specification dietary factors affecting risk nmosd great valuepmid34461362 doi101016 jclineuro2021106903,0.0
t2 relaxometry evidence microstructural changes diffusely abnormal white matter relapsingremitting multiple sclerosis clinically isolated syndrome impact visuomotor performance j magn reson imaging 2021 may 6 doi 101002 jmri27661 online ahead printabstractbackground although diffusely abnormal white matter dawm commonly seen multiple sclerosis ms rarely considered clinical imaging studiespurpose evaluate quantitative markers microstructural changes dawm patients clinically isolated syndrome cis relapsingremitting ms rrms relation ms lesions degree neurocognitive impairment using multiecho spin echo mese proton density pdtot2 sequencestudy type prospective crosssectionalpopulation thirtyseven rrms patients 33 cis patients 52 healthy controlsfield strength sequence 15 t t1 t2weighted fluidattenuated inversion recovery mese sequencesassessment long t2 short t2 myelin water fraction mwf values estimated indices intra extracellular water content myelin content respectively dawm posterior periventricular normal appearing white matter nawm focal ms lesions classified according signal intensity t1 sequences patients also administered battery neuropsychological testsstatistical tests comparisons t2 mwf values dawm nawm ms lesions examined using twoway mixed analyses variance associations grooved pegboard performance t2 mwf values dawm nawm assessed using pearson correlation coefficientsresults t2 mwf values dawm intermediate respective values nawm t1 hypointense focal lesions difference respective values dawm t1isointense lesions t2 values dawm strongly associated visuomotor performance cis patientsdata conclusion intra extracellular water myelin water content dawm similar t1isointense lesions predict visuomotor performance cis patientslevel evidence 2 technical efficacy stage 2pmid33960066 doi101002 jmri27661,1.0
prevalence comorbidities multiple sclerosis patients neurogenic bladder prog urol 2021 apr 30s11667087 20 307144 doi 101016 jpurol202010011 online ahead printabstractaims aim study define prevalence comorbidities among multiple sclerosis patients lower urinary tract symptomsmethods retrospective study data collected prospectively january 2000 march 2016 carried using database comorbidities divided several classes according international classification diseases icd10 results one hundred fiftyfive patients included neurogenic bladder 150 96 overactive bladder edss score was6 44 patients 28 comorbidities present 79 50 9 frequent ones cardiovascular 14 2 endocrinological 10 3 urological 8 4 abdominal 7 7 overweight bmi25 observed 63 40 strict relationship found bmi stress urinary incontinence p0001 well voiding dysfunction p0003 without significant association bmi overactive bladderconclusion prevalence comorbidities important ms 50 significant association found overweight stress urinary incontinence voiding dysfunction knowledge comorbidities ms important since presence urinary symptoms related neurogenic bladder must lead specific treatmentlevel evidence 3pmid33941463 doi101016 jpurol202010011,0.0
autoinjector smart device emergency cum personal therapy saudi pharm j 2021 oct 29 10 12051215 doi 101016 jjsps202109004 epub 2021 sep 20abstractautoinjectors selfinjectable devices important class medical devices can deliver drugs subcutaneous intramuscular route enclose prefilled syringes cartridges driven spring system major benefits device easy selfadministration improved patient compliance reduced anxiety dosage accuracy immediate treatment emergency conditions anaphylaxis migraine status epilepticus chronic conditions like psoriasis diabetes multiple sclerosis rheumatoid arthritis reformulation firstgeneration biologics technical advancements innovative designs patient compliance overwhelming interest selfadministration made entry autoinjectors use review intensive efforts made exploring different types currently available autoinjectors management emergency chronic diseasespmid34703373 pmcpmc8523323 doi101016 jjsps202109004,0.0
can diplopia complaint reduced telerehabilitation multiple sclerosis patient pandemic case report neurol sci 2021 mar 24 doi 101007 s10072021051942 online ahead printabstracthospital visits regular rehabilitation chronic patients due covid19 pose risk therefore patients chronic illnesses need regular rehabilitation victims pandemic process fear infected deprived chance symptoms rehabilitated therefore extremely important rehabilitate individuals chronic illnesses need rehabilitation telerehabilitation study aimed show effect cawthornecooksey exercises applied telerehabilitation eye movements vision quality life patient suffering diplopia due multiple sclerosis ms found cawthornecooksey exercises improve quality life reduce complaints diplopia ms patients diplopia addition patient verbally stated balance increased cawthornecooksey exercises result cawthornecooksey exercises rehabilitation method gives positive results treatment diplopia recommended apply method via telerehabilitationpmid33763810 doi101007 s10072021051942,0.0
pain intensity pain interference people progressive multiple sclerosis compared people relapsingremitting multiple sclerosis arch phys med rehabil 2021 may 25s00039993 21 003932 doi 101016 japmr202105003 online ahead printabstractobjective describe pain intensity interference people progressive multiple sclerosis ms compare people relapsingremitting ms rrms identify common unique factors associated pain intensity people progressive ms rrmsdesign observational crosssectional analysis using baseline data longitudinal survey quality life participants mssetting communityparticipants 573 adults ms progressive ms n 142 rrms n 431 interventions applicablemain outcome measures average pain intensity measured 11point numerical rating scale pain interference measured promis pain interference shortformresults participants progressive ms reported moderate average pain intensity 322 250 elevated pain interference tscore 5555 913 differ significantly rrms average pain intensity pain interference common factors associated higher average pain intensity severe disability lower education level unemployed current smoking progressive ms older age associated lower average pain intensityconclusions pain intensity interference similar across ms types addition assessing treating pain important screen modifiable painrelated factors smoking cessation populationpmid34048792 doi101016 japmr202105003,0.0
economic burden highly active relapsingremitting multiple sclerosis patients french national health insurance database expert rev pharmacoecon outcomes res 2021 jun 24 doi 101080 1473716720211945926 online ahead printabstractbackground healthcare management highly activerelapsingremitting multiple sclerosis harrms patients complex whole multiple sclerosis ms population study assessed related economic burden national health insurances nhis perspectiveresearch design methods study based french nhi databases using individual data billing reimbursement outpatient hospital healthcare consumption paid sick leave disability pension 20102017results 9 596 harrms adult patients data 7 960 patients analyzed least 2 years followup mean annual cost patient 29 813 drugs represented 40 cost hospital care 33 disability pensions 9 healthcare professionals visits combined 8 among 3 024 patients 60 yearsold disability pension disability pension cost 7 168 patient year among 3 807 patients paid sick leave sick leave cost 1 956 patient year mean costs 2 246 patient higher first year increased 1 444 2010 2015 5 188 increase drugrelated expenditures 634 increase healthcare professionals visits expenditures 4 529 decrease hospital care expendituresconclusions cost healthcare sick leaves disability pensions harrms patients twice high previously reported cost ms patientspmid34165377 doi101080 1473716720211945926,0.0
emerging deep learning techniques using magnetic resonance imaging data applied multiple sclerosis clinical isolated syndrome patients review exp ther med 2021 oct 22 4 1149 doi 103892 etm202110583 epub 2021 aug 9abstractcomputeraided diagnosis systems aim assist clinicians early identification abnormal signs order optimize interpretation medical images increase diagnostic precision multiple sclerosis ms clinically isolated syndrome cis chronic inflammatory demyelinating diseases affecting central nervous system recent advances deep learning dl techniques led novel computational paradigms ms cis imaging designed automatic segmentation detection areas interest automatic classification anatomic structures well optimization neuroimaging protocols end several publications presenting artificial intelligencebased predictive models aiming increase diagnostic accuracy facilitate optimal clinical management patients diagnosed ms cis current study presents thorough review covering dl techniques applied ms cis recent years shedding light current advances limitationspmid34504594 pmcpmc8393268 doi103892 etm202110583,1.0
human endogenous retrovirus type w envelope multiple sclerosis demyelinating lesions shows unique solubility antigenic characteristics virol sin 2021 mar 26 doi 101007 s12250021003720 online ahead printabstractin multiple sclerosis ms human endogenous retrovirus w family hervw envelope protein phervw env limits remyelination induces microgliamediated neurodegeneration better understand role examined soluble phervw antigen ms brain lesions detected specific antibodies physicochemical antigenic characteristics confirmed differences phervw env syncytin1 phervw env monomers trimers remained associated membranes hexamers selfassembled monomers soluble macrostructure involving sulfatides ms brain extracellular hexamers stabilized internal hydrophobic bonds external hydrophilic moieties hervw studies ms also suggest diffusible antigen may correspond previously described highmolecularweight neurotoxic factor secreted ms bcells thus represents major agonist ms pathogenesis adapted methods now needed identify encoding herv provirus es affected cells dna properties origin ms brain phervw env soluble antigen will allow better understanding role hervs ms pathogenesis present results anyhow pave way accurate detection different forms phervw env antigen appropriate conditions remained unseen nowpmid33770381 doi101007 s12250021003720,1.0
ocrelizumab can used multiple sclerosis rituximabinduced serum sickness case report rev neurol paris 2021 feb 19s00353787 21 000321 doi 101016 jneurol202011003 online ahead printno abstractpmid33618890 doi101016 jneurol202011003,0.0
tuberous sclerosis negative genetic testing multiple cerebral cavernomas new association case report exp ther med 2021 oct 22 4 1183 doi 103892 etm202110617 epub 2021 aug 16abstracttuberous sclerosis complex tsc autosomal dominant disorder multisystemic involvement usually resulting mutations tuberous sclerosis 1 tsc1 tsc2 genes however 10 25 patients exhibit mutations cerebral cavernous malformations ccms capillaryvenous malformations can asymptomatic cause variable neurological manifestations including seizures familial ccms recognized conditions specific dermatological lesions associated present case 31yearold female tsc diagnosed age 18 years presented negative genetic testing admitted department 2019 sudden increased frequency focal seizures patient examination revealed multiple facial intraoral angiofibroma diplopia right hemihypoesthesia brisk deep tendon reflexes distal leg paresthesia videoeeg indicated frontal paramedian epileptogenic focus cerebral magnetic resonance imaging mri angiomri identified multiple frontoparietal cortical tubers well multiple ccms evidence bleeding one antiepileptic drug aed mtor inhibitor treatment seizure frequency significantly improved short period time first reported case tuberous sclerosis negative genetic testing associated multiple cerebral cavernoma complex patients require multidisciplinary management detailed genetic testing increasing knowledge neurocutaneous disorderspmid34475973 pmcpmc8406763 doi103892 etm202110617,0.0
trpa1 involvement depression anxietylike behaviors progressive multiple sclerosis model mice brain res bull 2021 jul 16s03619230 21 002112 doi 101016 jbrainresbull202107011 online ahead printabstractprogressive multiple sclerosis pms neurological disease associated development depression anxiety treatments available unsatisfactory transient receptor potential ankyrin 1 trpa1 cationic channel activated reactive compounds blockage receptor can reduce depression anxietylike behaviors naive mice thus investigated role trpa1 depression anxietylike behaviors pms model mice pms model induced c57bl 6 female mice experimental autoimmune encephalomyelitis eae nine days pmseae induction behavioral tests tail suspension elevated plus maze tests performed verify effects sertraline positive control selective trpa1 antagonist a967079 antioxidants lipoic acid apocynin prefrontal cortex hippocampus collected evaluate biochemical inflammatory markers pmseae induction cause locomotor changes triggered depression anxietylike behaviors reversed sertraline a967079 lipoic acid apocynin treatments neuroinflammatory markers aif1 gfap il1 il17 tnf increased mices hippocampus moreover model alter trpa1 rna expression levels hippocampus decrease trpa1 levels prefrontal cortex moreover pmseae induced increase nadph oxidase superoxide dismutase activities trpa1 endogenous agonist levels hydrogen peroxide 4hydroxynonenal trpa1 plays fundamental role depression anxietylike behaviors pmseae model thus possible pharmacological target treating symptoms pmspmid34280479 doi101016 jbrainresbull202107011,0.0
diagnostic approach multiple sclerosis mri update clin imaging 2021 may 31 78276285 doi 101016 jclinimag202105025 online ahead printabstractalthough neurological examination medical history first important steps towards diagnosis multiple sclerosis ms mri taken prominent role diagnostic workflow especially since implementation mcdonald criteria however applying mr imaging features diseases must excluded ms favoured likely diagnosis prognosis earliest possible correct diagnosis ms crucial since increasingly effective disease modifying therapies available different forms clinical manifestation progression review deals significance mri diagnostic workup ms special regard daily clinical practice recommended mri protocols baseline followup examinations summarized typical ms lesion patterns green flags four defined cns compartments introduced pivotal recognition neurological aspects well imaging findings atypical ms red flags addition routinely assessment aquaporin4igg antibodies specific neuromyelitis optica spectrum disorders nmosd well knowledge associated lesion patterns mri recommended mistaken identity lesions ms consecutive implementation disease modifying therapies ms can worsen course nmosdpmid34174655 doi101016 jclinimag202105025,0.0
rate leptomeningeal enhancement pediatric myelin oligodendrocyte glycoprotein antibodyassociated encephalomyelitis j child neurol 2021 oct 36 11 10421046 doi 101177 08830738211025867abstractintroduction myelin oligodendrocyte glycoprotein antibodies mogabs associated demyelinating diseases leptomeningeal enhancement occurs 6 adult mogabs patients rates pediatric mogabs patients unknownmethods retrospective review pediatric mogabs patients performedresults twentyone patients 7 boys 14 girls included average age 86 years range 215 years seven 21 33 pediatric mogabs patients leptomeningeal enhancement two patients relapses manifested leptomeningeal enhancement alone another patient presented seizures encephalopathy aseptic meningitis without demyelinating lesions cerebrospinal fluid pleocytosis seen leptomeningeal 4 7 patients nonleptomeningeal enhancement 10 14 patients interestingly 3 patients leptomeningeal enhancement normal cerebrospinal fluid white blood cell count cortical edema likely patients leptomeningeal enhancement p 0263 conclusion expand clinical spectrum antimog antibodyassociated disorder patients recurrent leptomeningeal enhancement without demyelinating lesions tested mog antibodiespmid34547933 doi101177 08830738211025867,1.0
physical activity social cognitive theory variable scores differ across symptom cluster severity groups multiple sclerosis disabil health j 2021 jun 29101163 doi 101016 jdhjo2021101163 online ahead printabstractbackground persons multiple sclerosis ms experience cooccurring symptoms termed symptom clusters can distinguished based mild moderate severe symptom severity termed symptom cluster severity physical activity pa may approach improving cooccurring symptomsobjective examined pa social cognitive theory sct variables differed symptom cluster groups associations sct variables pa moderated symptom cluster groupsmethods secondary analysis participants ms n 205 enrolled crosssectional study trend analyses conducted determine devicemeasured selfreported pa sct variables ie social support selfefficacy outcome expectations goal setting planning impediments decreased increased symptom cluster severity spearman rho rankorder correlations conducted pa measures sct variables within symptom cluster groupresults linear trend analyses indicated selfreported pa declined increased symptom cluster severity groups f 490 p 003 linear trend analyses indicated significant differences among symptom cluster severity groups social support f 3143 p 0001 exercise selfefficacy f 2255 p 0001 barrier selfefficacy f 1148 p 0001 outcome expectations f 698 p 0009 impediments f 3441 p 0001 differential associations moderate magnitude correlations three sct variables associated pa mild group ie selfefficacy goal setting planning two moderate group ie social support goal setting four severe group ie selfefficacy outcome expectations planning social support conclusions research warranted examining use sctbased behavior change techniques promoting pa improving symptom clusters persons mspmid34219037 doi101016 jdhjo2021101163,1.0
kurt jellinger 90 contribution neuroimmunology j neural transm vienna 2021 jun 10 doi 101007 s00702021023584 online ahead printabstractthis review honors kurt jellinger 90th birthday one outstanding neuropathologists contributed immensely neuroscience due vast experience collection excellently documented autopsy cases two many insightful reports highlighted one report focuses pathogenesis inflammatory demyelinating diseases investigates neuropathology autopsy tissue patient developed mslike disease repeated treatment lyophilized bovine brain cells 1958 60 years later reinvestigation historic samples 2015 subsequent mrna isolation next generation sequencing reconstruction antibody succeeded identifying myelin oligodendrocyte glycoprotein mog target antigen provided missing element pathomechanisms classic eae animal models transfer disease process humans second significant example kurt jellingers contribution neuroscience report role ms development alzheimers disease ad found ad pathology present extent demyelinated nondemyelinated cortical areas ms incidence ad pathology elderly ms patients comparable normalaging population indicates chronic inflammation ms cortex alone significantly predispose development cortical ad pathology findings possible due broad collection extremely welldefined material established kurt jellinger ultimately continues contribute translational neuroscience even decades laterpmid34110492 doi101007 s00702021023584,1.0
supporting adaptation announcement multiple sclerosis rev infirm 2021 oct 70 274 3739 doi 101016 jrevinf202107010 epub 2021 jul 19abstractmultiple sclerosis ms disease often begins young adulthood least 2 500 new cases diagnosed year france leading cause severe nontraumatic disability among young adults announcement ms constitutes brutal intrusion life subject carers accompany process cognitive emotional adjustment inevitable order learn live diseasepmid34565536 doi101016 jrevinf202107010,0.0
administration covid19 vaccines immunocompromised patients int immunopharmacol 2021 jul 28 99108021 doi 101016 jintimp2021108021 online ahead printabstractsince beginning vaccination programs covid19 different countries several populations patients specific immunological conditions considered priorities immunization regard patients autoimmune diseases receiving immunosuppressive agents anticancer therapies need special attention however confirmed data presently available regarding covid19 vaccines populations due exclusion conducted clinical trials given probable suppression overactivation immune system patients reaching consensus vaccination critical besides gathering data conducting trials probably clarify matter future review besides brief available covid19 vaccines considerations available knowledge administering similar vaccines patients cancer hematopoietic stem cell transplantation solid organ transplantation multiple sclerosis ms inflammatory bowel disease ibd rheumatologic dermatologic autoimmune disorders summarized help decision making discussed liveattenuated viruses avoided groups employed present covid19 vaccines thus main concern regarding efficacy met using potent covid19 vaccine moreover vaccination timing maximum efficacy decided according patients condition indicated medications guides provided postvaccination monitoring also advised ensure adequate immune response studies area urgently warrantedpmid34352567 doi101016 jintimp2021108021,0.0
stress related covid19 pandemic trigger disease activity multiple sclerosis case report neurol sci 2021 jul 23 doi 101007 s10072021054425 online ahead printno abstractpmid34297265 doi101007 s10072021054425,0.0
environmental lifestyle factors relationships ms unique relapsingonset ms #39 factors affecting risk relapsing progressive onset multiple sclerosis#39 hedstrom colleagues j neurol neurosurg psychiatry 2021 may 13jnnp2020325990 doi 101136 jnnp2020325990 online ahead printno abstractpmid33986118 doi101136 jnnp2020325990,0.0
depression multiple sclerosis bidirectional mendelian randomisation study mult scler 2021 feb 191352458521996601 doi 101177 1352458521996601 online ahead printabstractdepression common multiple sclerosis ms however underlying mechanism relationship remains unknown study examined putative causal relationship depression ms using bidirectional mendelian randomisation mr framework using latest genomewide association study data available 168 nonmajor histocompatibility complex mhc independent variants associated ms 96 independent genetic variants associated depression susceptibility used maximum likelihood weighted median inverse variance weighted method mregger regression analyses performed significant risk development ms persons carrying variants associated depression risk depression individuals genetically susceptible mspmid33605804 doi101177 1352458521996601,0.0
low rate intrathecal baclofen pump catheterrelated complications longterm study 100 adult patients associated reinforced catheter neuromodulation 2021 may 11 doi 101111 ner13412 online ahead printabstractobjectives intrathecal baclofen itb costeffective therapy patients severe spasticity common complications catheterrelated complications crcs including kinking occlusion blockage migration fracture disconnection csf leak objective determine crc rate large cohort adults newly implanted itb pump systems polymer reinforced silicone cathetersmaterials methods retrospective study prospectively maintained database consisting patients undergone implantation itb pump systems ascenda medtronic minneapolis catheters 2013 2020 sevenyear period 141 patients underwent itb pump system implantations 126 minimum oneyear followupresults 126 patients minimum one year followup average 43 month range 1289 average age 51 years 63 male severe spasticity due spinal cord injury 38 traumatic brain injury 15 cerebral palsy 13 multiple sclerosis 11 stroke 10 13 nine 71 crcs occurred 7 56 patients median 6 mo postimplant 5 intrathecal catheter occlusions range 352 months postimplant two fractures one patient 6 months one disconnection catheter pump interface 2 months one due kinking 84 months migrations occurredconclusions reported crcs high itb pump systems ours first large cohort longterm study crcs related reinforced catheters additionally low crc rate compares favorably previously published data thus implantation reinforced catheters may associated low crc ratepmid33974333 doi101111 ner13412,0.0
multiple sclerosis relapses associated mrna covid19 vaccine nat rev neurol 2021 sep 2 doi 101038 s41582021005611 online ahead printno abstractpmid34475567 doi101038 s41582021005611,0.0
physical activity selfreported sleep quality adults multiple sclerosis disabil health j 2021 jun 11101133 doi 101016 jdhjo2021101133 online ahead printabstractbackground fourfold higher prevalence sleep problems multiple sclerosis ms general populationobjective study examined crosssectional associations among devicemeasured sedentary physical activity behavior perceived sleep quality adults msmethods adults ms n 290 completed pittsburgh sleep quality index psqi wore accelerometer seven days providing measure time spent sedentary behavior light physical activity lpa moderatetovigorous physical activity mvpa using msspecific cutpoints conducted multiple linear regression analysis identify independent contributions variables explaining psqi scoresresults overall model accounted 2 variance global psqi scores mvpa significantly independently associated global psqi scores 0123 p 0045 partial r 0118 accounting average wear time sedentary behavior time spent lpa significant associations psqi global scoreconclusions results suggest time spent mvpa may associated better sleep quality adults ms adults ms spend sufficient time physical activity researchers evaluate relationships longitudinal study designs behavior change interventions physical activity may provide unique opportunity improve sleep quality outcomespmid34193388 doi101016 jdhjo2021101133,0.0
impact genetic variation molecular mimicry anoctamin2 epsteinbarr virus nuclear antigen 1 multiple sclerosis immunol lett 2021 jul 23s01652478 21 001164 doi 101016 jimlet202107007 online ahead printno abstractpmid34310987 doi101016 jimlet202107007,0.0
effect acupuncture cytokine levels persons multiple sclerosis randomized controlled trial j altern complement med 2021 jul 15 doi 101089 acm20200510 online ahead printabstractbackground cytokines found play role disease activity multiple sclerosis ms previous studies indicate acupuncture can affect cytokine levels persons inflammatory diseases objectives aim study investigate effect acupuncture cytokine levels healthrelated quality life hrqol persons ms materials methods singleblind randomized controlled trial performed participants n 66 randomized three groups real acupuncture sham acupuncture reference participants real acupuncture sham groups received six treatments period 4 weeks serum levels 11 pro antiinflammatory cytokines ifn il1 il6 il8 il12p70 il13 tnf il10 il4 il2 il17a assessed baseline 2 4 weeks treatment 4 weeks final treatment changes hrqol assessed using functional assessment multiple sclerosis questionnaire results statistically significant differences plasma levels three groups seen either cytokines differences groups hrqol conclusions study authors demonstrate 4week acupuncture treatment measurable effect plasma levels seven selected cytokines hrqol among people ms trial registered isrctn registry isrctn34352011pmid34265224 doi101089 acm20200510,0.0
autoimmune glomerulonephritis multiple sclerosis patient cladribine treatment mult scler 2021 jun 2413524585211022719 doi 101177 13524585211022719 online ahead printabstractbackground oral cladribine approved diseasemodifying drug treatment relapsing multiple sclerosis controlled clinical trials well post marketing safety assessments autoimmune conditions yet reported specific side effect cladribineobjective results report case antiglomerular basement membrane antibodymediated glomerulonephritis occurred shortly fourth cladribine treatment cycleconclusion neurologists attentive development secondary autoimmunity cladribinetreated patientspmid34165361 doi101177 13524585211022719,0.0
notch2nlcrelated repeat expansion disorders expanding group neurodegenerative disorders neurol sci 2021 aug 1 doi 101007 s10072021054983 online ahead printabstractthe notch2nlc gene 5 untranslated region utr ggc repeat expansion mutations identified genetic contributor neuronal intranuclear inclusion disease niid 2019 since number reported cases notch2nlc ggc repeat expansion asian european populations increased rapidly indicating expanded mutation leads onset progression niid also may play important role multiple progressive neurological disorders including parkinsons disease essential tremor multiple system atrophy alzheimers disease frontotemporal dementia amyotrophic lateral sclerosis leukoencephalopathy oculopharyngodistal myopathy type 3 nevertheless underlying pathogenic mechanism notch2nlc 5 utr region ggc repeat expansion disorders remains largely unknown review aims present recent breakthroughs mutation improve knowledge newly defined spectrum disease notch2nlcrelated repeat expansion disorderpmid34333668 doi101007 s10072021054983,0.0
spinal fluid igg antibodies patients demyelinating diseases bind multiple sclerosisassociated bacteria j mol med berl 2021 jun 8 doi 101007 s0010902102085z online ahead printabstracta panel 10 igg enzymelinked immunosorbent assays elisas developed detection antimicrobial immune responses cerebrospinal fluid csf patients demyelinating diseases dd antimicrobial elisa assays follow prior human brain tissue rna sequencing studies established multiple sclerosis ms microbial candidates lysates included elisa panel derived akkermansia muciniphila atopobium vaginae bacteroides fragilis lactobacillus paracasei odoribacter splanchnicus pseudomonas aeruginosa cutibacterium propionibacterium acnes fusobacterium necrophorum porphyromonas gingivalis streptococcus mutans csf responses patients demyelinating diseases dd n 14 compared neurological diseases ond n 8 controls n 13 commercial positive negative control csf specimens run assay elisa index values derived specimen 10 bacterial lysates csf reactivity significantly higher dd group compared controls akkermansia atopobium bacteroides lactobacillus odoribacter fusobacterium four 11 tested dd group subjects elevated antibody indexes least one 10 bacterial species suggesting intrathecal antibody production csf serological study supports hypothesis several previously identified ms candidate microbes contribute demyelination patients key messages panel 10 igg enzymelinked immunosorbent assays elisas developed detection antimicrobial immune responses cerebrospinal fluid csf patients demyelinating diseases including multiple sclerosis acute disseminated encephalomyelitis csf reactivity significantly higher demyelination group compared controls bacteria akkermansia atopobium bacteroides lactobacillus odoribacter fusobacterium several demyelination subjects elevated antibody indexes least one 10 antigens suggesting least limited intrathecal production antibacterial antibodies csf serological study supports hypothesis several previously identified ms candidate microbes contribute demyelination patientspmid34100959 doi101007 s0010902102085z,1.0
curing multiple sclerosis know we#39 re ann neurol 2021 jul 2 doi 101002 ana26155 online ahead printno abstractpmid34216039 doi101002 ana26155,1.0
mri correlates cognitive improvement homebased eeg neurofeedback training patients multiple sclerosis pilot study j neurol 2021 mar 30 doi 101007 s00415021105309 online ahead printabstractobjective neurofeedback training may improve cognitive function patients neurological disorders however underlying cerebral mechanisms improvements poorly understood therefore aimed investigate mri correlates cognitive improvement eegbased neurofeedback training patients ms pwms methods fourteen pwms underwent ten neurofeedback training sessions within 34 weeks home using telerehabilitation system half pwms n 7 responders learned selfregulate sensorimotor rhythm smr 1215 hz visual feedback improved cognitively training whereas remainder nonresponders n 7 diffusiontensor imaging restingstate fmri brain performed training analyzed fractional anisotropy fa functional connectivity fc defaultmode sensorimotor smn salience network sal results baseline responders nonresponders comparable regarding sex age education disease duration physical cognitive impairment mri parameters training compared nonresponders responders showed increased fa fc within sal smn cognitive improvement correlated increased fc sal correlation trend increased fa observedconclusions exploratory study suggests successful neurofeedback training may lead cognitive improvement also increases brain microstructure functional connectivitypmid33786666 doi101007 s00415021105309,0.0
antiinflammatory therapy cholinergic purinergic modulation multiple sclerosis associated sarscov2 infection mol neurobiol 2021 jul 11 doi 101007 s12035021024640 online ahead printabstractthe virus acute respiratory syndrome coronavirus 2 sarscov2 etiologic agent coronavirus disease 2019 covid19 initially responsible outbreak pneumonia wuhan china due high level contagion dissemination become pandemic clinical picture varies mild critical cases however signs already show neurological problems sensory loss neurological diseases thus patients multiple sclerosis ms infected new coronavirus likely develop severe conditions addition worsening disease due high level proinflammatory cytokines closely associated increased mortality covid19 ms increase uncontrolled exaggerated characterizing cytokine storm possible therapy neuronal inflammation modulation cholinergic antiinflammatory pathway since acetylcholine ach acts reduce proinflammatory cytokines acts directly brain released cholinergic neurons well acting cells immune blood cells addition due tissue damage exacerbated release adenosine triphosphate atp potentiating inflammatory process activating purinergic receptors act directly neuroinflammation positively modulate inflammatory cycle associated neurological pathologies greater expression p2x7 cells microglia positively activates immune inflammatory response thus administration blockers receptor can act conjunction action ach anticholinergic inflammatory pathway finally will reduction cytokine storm triggered hyperinflammation well level mortality patients multiple sclerosis infected sarscov2 development possible neurological damagepmid34247339 doi101007 s12035021024640,0.0
evaluation effect mannuronic acid novel nsaid immunosuppressive properties expression socs1 socs3 ship1 traf6 genes serum level il6 tnfalpha patients multiple sclerosis j clin pharmacol 2021 apr 28 doi 101002 jcph1879 online ahead printabstractmultiple sclerosis ms described chronic inflammatory demyelinating disease central nervous system autoimmune basis frequent reason nontraumatic disability youths efficacy safety dmannuronic acid m2000 novel immunosuppressive drug patented pct ep2017 067920 shown experimental model ms also phase ii clinical trial effects m2000 socs1 socs3 traf6 ship1 gene expression also serum level il6 tnf secondary progressive multiple sclerosis spms patients assessed study study 14 spms patients 14 healthy subjects control group recruited phase ii clinical trial clinical trial identifier irct2016111313739n6 gene expression socs1 socs3 traf6 ship1 measured baseline 6 months therapy m2000 using quantitative realtime pcr method furthermore serum level il6 tnf assessed elisa method results showed gene expression socs1 socs3 ship1 increased 6 months therapy m2000 ms patients moreover serum level il6 tnf patients declined compared baseline statistically significant results study demonstrated m2000 immunosuppressive properties upregulate socs1 socs3 ship1 genes patients spms article protected copyright rights reservedpmid33908653 doi101002 jcph1879,1.0
transcriptomic analysis peripheral monocytes upon fingolimod treatment relapsing remitting multiple sclerosis patients mol neurobiol 2021 jun 28 doi 101007 s1203502102465z online ahead printabstractfingolimod fty secondline oral drug approved relapsing remitting multiple sclerosis rrms acts preventing lymphocyte migration outside lymph nodes moreover several lines evidence suggest also inhibits myeloid cell activation study investigated transcriptional changes induced fty monocytes order better elucidate mechanism action cd14+ monocytes collected 24 rrms patients sampled baseline 6 months treatment rna profiles obtained nextgeneration sequencing conducted pathway subpaths analysis followed centrality analysis cellspecific interactomes differentially expressed genes degs investigated also predictive role baseline monocyte transcription profile influencing response fty therapy observed marked downregulation effect 60 downregulated vs 0 upregulated genes downregulated degs resulted related monocyte activation migration like il7r ccr7 wnt signaling mediators lef1 tcf7 involvement wnt signaling also confirmed subpaths analyses furthermore pathway network analyses showed involvement processes related immune function cell migration baseline transcriptional profile hla class ii gene hladqa1 hladpa1 associated evidence disease activity 2 years treatment data support evidence fty induces major transcriptional changes monocytes mainly regarding genes involved cell trafficking immune cell activation baseline transcriptional levels genes associated antigen presenting function associated disease activity 2 years fty treatmentpmid34181235 doi101007 s1203502102465z,0.0
clinical applications myelin plasticity remyelinating therapies multiple sclerosis ann neurol 2021 aug 17 doi 101002 ana26196 online ahead printabstractcentral nervous system demyelination multiple sclerosis ms subsequent axonal degeneration represents major cause clinical morbidity learning salient experiences stimulation neuronal activity induce new myelin formation rodents animal models demyelination remyelination can enhanced via experience activitydependent mechanisms furthermore preliminary studies ms patients supports use neuromodulation rehabilitation exercises symptomatic improvement suggesting interventions may represent nonpharmacological strategies promoting remyelination review literature myelin plasticity processes assess potential leverage mechanisms develop remyelinating therapies article protected copyright rights reservedpmid34402546 doi101002 ana26196,1.0
corneal subbasal nerve plexus evaluation vivo confocal microscopy multiple sclerosis potential new biomarker curr eye res 2021 mar 18 doi 101080 0271368320211904509 online ahead printabstractpurpose aim study aims evaluate corneal subbasal nerve plexus morphology vivo corneal confocal microscopy ccm multiple sclerosis ms patients explore potential ability distinguish ms patients healthy subjectsmaterials methods crosssectional study including sixty ms patients twentytwo healthy subjects expanded disability status scale edss used assess neurological disability participants underwent full ophthalmology evaluation ccm optical coherence tomography oct corneal nerve fibre density cnfd branch density cnbd fibre length cnfl fibre tortuosity cnft analysed generalized additive regression models used analyse dataresults compared controls ms patients lower cnfd cnbd cnfl p0001 higher cnft p0002 area roc curve distinguish ms patients healthy controls cnfd cnbd 084 95ci 075 093 95ci 075 092 respectively nonlinear association edss cnfd found initial density increase followed significant decrease severe disability status edss associated cnfl cnbd values significantly lower patients edss25 206 mm mm2 95ci 384 028 p0027 870 branches mm2 95ci 1469 271 p0006 respectively optic neuritis history influence ccm parametersconclusions results confirm ccm parameters potential differentiate ms patients healthy subjects influenced previous history significant relationship patients disability corneal nerves morphology also foundpmid33734930 doi101080 0271368320211904509,0.0
role eef1d disease pathogenesis narrative review ann transl med 2021 oct 9 20 1600 doi 1021037 atm215025abstractobjective purpose paper investigate role mechanism eef1d various diseases especially tumorigenesis development explore possibility eef1d biological targetbackground eef1d part eef1 protein complex can produce four protein isoforms three short isoforms used translation elongation factors three short isoforms play role antiaging regulating cell cycle promoting occurrence development malignant tumors longform isoform plays role development nervous systemmethods searched pubmed web science databases literature january 2021 using relevant keywords including eef1d eukaryotic translation elongation factor 1 delta translation elongation factor translation elongation factor cancer translation elongation factor nervous system disease created overview literature summarized results paperconclusions review relevant articles found eef1d obviously overexpressed variety tumors can regulate proliferation tumor cells tumor growth well play role tumor invasion eef1d likely become new biological target tumor therapy diagnosispmid34790806 pmcpmc8576685 doi1021037 atm215025,0.0
#39 they#39 re getting taste world#39 qualitative study people multiple sclerosis#39 experiences accessing health care covid19 pandemic australian capital territory health expect 2021 jul 6 doi 101111 hex13284 online ahead printabstractbackground people multiple sclerosis ms often immunocompromised require complex care engage variety healthcare providers manage healthobjective elucidate people ms experiences accessing health care covid19 pandemic australiadesign qualitative study involving semistructured interviews thematic analysissettings participants eight adults clinical diagnosis ms participated telephone video call interviews june july 2020results participants aware ms made vulnerable contracting covid19 cases usual care postponed sought circumstances warranted risk facetoface consultation benefits telehealth consultations included improved access convenience contactfree comparison video consultations via telephone considered less personal limited capacity read body language physical examination participants hoped incorporate telehealth future healthcare routinesdiscussion conclusion personal risk assessment trust healthcare professionals determinants mode people ms accessed health care covid19 pandemic telehealth valuable tool mitigate covid19 transmission enabling contactfree consultations people ms may find specific value video consultations enable visualization physical function need training support clinicians conduct remote consultationspatient public contribution study conducted team comprised four people ms neurologist four health services researcherspmid34227728 doi101111 hex13284,0.0
nitrosative stress parameters level oxidized dna bases patients multiple sclerosis metab brain dis 2021 aug 21 doi 101007 s11011021007865 online ahead printabstractmultiple sclerosis ms neurodegenerative disease various factors affecting etiology overproduction nitric oxide subsequent lesions biopolymers possible causes disease study aimed measure relevant nitrosative oxidative stress biomarkers level modified dna bases patients ms parameter assayed 25 patients ms 25 healthy controls study involved detecting blood plasma serum nitric oxide metabolites chemiluminescence detector sievers noa280i malondialdehyde mda measurements thiobarbituric acid reactive substance tbars assay detection oxidized purines pyrimidines enzymemodified comet assay statistical analysis results performed oneway analysis variance anova unpaired t test comparison less three data sets dna singlestrand breaks levels modified purines pyrimidines well nitrite nitrate levels plasma serum samples significantly higher patients ms healthy controls contrary mda levels appeared lower patients mspmid34417942 doi101007 s11011021007865,0.0
multiple sclerosis prevalence #39 central vein#39 sign white matter lesions gadoliniumenhanced susceptibilityweighted images neuroradiol j 2021 apr 1919714009211008750 doi 101177 19714009211008750 online ahead printabstractaims evaluate prospectively whether intravenous gadolinium injection improve detection central vein sign susceptibilityweighted imaging sequences obtained 15 t magnetic resonance scanner patients multiple sclerosis compared unenhanced susceptibilityweighted imagesmaterials methods prospective institution review boardapproved study included 19 patients affected multiple sclerosis six men 13 women mean age 408 years range 2074 years patients relapsingremitting clinical subtype 95 cases one 5 patient primary progressive clinical subtype multiple sclerosis t2weighted images fluidattenuated inversion recovery images unenhanced contrastenhanced susceptibilityweighted images evaluated consensus two neuroradiologists presence central vein sign readers blinded magnetic resonance imaging reports clinical information presence localisation focal hyperintense white matter lesions discordance readers resolved joint review recorded images additional neuroradiologistresults total 317 multiple sclerosis lesions analysed central vein sign higher prevalence detection rate gadoliniumenhanced susceptibilityweighted images 272 317 lesions 86 compared unenhanced susceptibilityweighted images 172 317 lesions 54 conclusion gadoliniumenhanced susceptibilityweighted imaging improves detection rate central vein sign multiple sclerosis lesionspmid33872085 doi101177 19714009211008750,0.0
th1 cd11c + b cell axis associated response plasmapheresis multiple sclerosis ann neurol 2021 aug 23 doi 101002 ana26202 online ahead printabstractobjective although plasmapheresis treatment option patients autoimmune neurological diseases treatment response varies greatly among patients main objective study find biological immune traits correlate beneficial responsemethods thoroughly analyzed immune phenotypes paired blood samples cohort 31 patients multiple sclerosis plasmapheresis parallel clinical evaluation treatment responseresults frequency ifn+ th1 cells persistently higher obtained benefit plasmapheresis responders nonresponders th1 cell frequency plasmapheresis provided high predictive value beneficial response achieving auc 0902 plasmapheresis treatment decreased inflammationrelated gene expressions th1 cells meanwhile ifng expression th1 cells positively correlated frequency cd11c+ b cells pathogenic role suggested several autoimmune diseases line vitro experiments showed cd11c+ b cells increase response exogenous ifn compared il4 secrete high amounts igg b cell receptor analysis indicated clonal expansion cd11c+ b cells takes place patients multiple sclerosis interestingly cd11c+ b cells showed unique gene expression profile decreased plasmapheresis treatment along immunoglobulin subsets circulationinterpretation taken together postulate th1 cell cd11c+ b cell axis involved treatment response plasmapheresis giving us clues better understanding complicated pathogenesis autoimmune diseases getting closer personalized therapy article protected copyright rights reservedpmid34424567 doi101002 ana26202,0.0
differential effects estradiol progesterone human t cell activation vitro eur j immunol 2021 jul 5 doi 101002 eji202049144 online ahead printabstractestradiol e2 progesterone p4 steroid hormones important regulation immune responses pregnancy increasing levels coincide improvement t cellmediated diseases multiple sclerosis ms although immuneendocrine interactions involved phenomenon relative contribution hormones known report direct comparison e2 p4mediated effects human cd4+ t cells key cells immune regulation t cells stimulated obtain different levels activation exposed broad range hormone concentrations activation level assessed cd69 cd25 expression flow cytometry secreted proteins n 196 measured culture supernatants using proximity extension assay electrochemiluminescence immunoassay found low activated cells pregnancyrelevant e2 concentrations increased activation secretion several immune inflammationrelated proteins p4 hand showed biphasic pattern serumrelated concentrations upregulated activation protein secretion placentarelevant concentrations induced prominent dampening irrespective initial activation level results demonstrate importance p4 major hormone immune modulation t cells pregnancy emphasize need evaluate potency treatment diseases like ms article protected copyright rights reservedpmid34223649 doi101002 eji202049144,0.0
pathophysiological function nongastrointestinal farnesoid x receptor pharmacol ther 2021 apr 22107867 doi 101016 jpharmthera2021107867 online ahead printabstractfarnesoid x receptor fxr influences bile acid homeostasis progression various diseases roles hepatic intestinal fxr enterohepatic transport bile acids metabolic diseases reviewed previously physiological pathophysiological functions fxr nongastrointestinal fxr received little attention thus roles fxr liver immune system nervous system cardiovascular system kidney pancreas beyond gastrointestinal system reviewed herein gain fxr function studies nongastrointestinal tissues revealed fxr signaling improved various experimentallyinduced metabolic immune diseases including nonalcoholic fatty liver disease type 2 diabetes primary biliary cholangitis sepsis autoimmune diseases multiple sclerosis diabetic nephropathy loss fxr promotes regulatory t cells production protects brain ischemic injury atherosclerosis inhibits pancreatic tumor progression downstream pathways regulated fxr diverse tissue cellspecific fxr found liganddependent ligandindependent activities may explain activation inhibition fxr signaling produce paradoxical even opposite effects experimental disease models fxr signaling frequently compromised diseases especially progressive stage rescuing fxr expression may provide promising strategy boosting therapeutic effect fxr agonists tissue cellspecific modulation nongastrointestinal fxr influence treatment various diseases review provides guide drug discovery clinical use fxr modulatorspmid33895191 doi101016 jpharmthera2021107867,0.0
concurrent axon myelin destruction differentiates xlinked adrenoleukodystrophy multiple sclerosis glia 2021 jun 17 doi 101002 glia24042 online ahead printabstractcerebral disease manifestation occurs two thirds males xlinked adrenoleukodystrophy cald fatally progressive left untreated early histopathologic studies categorized cald inflammatory demyelinating disease led repeated comparisons multiple sclerosis ms aim study revisit relationship axonal damage myelin loss cald applied novel immunohistochemical tools investigate axonal damage myelin loss myelin repair autopsy brain tissue eight cald 25 ms patients found extensive severe acute axonal damage cald already prelesional areas defined microglia loss relative myelin preservation contrast ms observe selective phagocytosis myelin concomitant decay entire axonmyelin unit cald lesion stages using novel marker protein actively remyelinating oligodendrocytes breast carcinomaamplified sequence bcas 1 show repair pathways activated oligodendrocytes cald regenerating cells however affected ongoing disease process provide evidence thatin contrast msselective myelin phagocytosis characteristic cald contrary data indicate acute axonal injury permanent axonal loss thus far underestimated features disease must come focus search biomarkers novel therapeutic approachespmid34137074 doi101002 glia24042,1.0
state art challenges classification studies electromechanical robotic devices neurorehabilitation scoping review eur j phys rehabil med 2021 may 27 doi 1023736 s1973908721069227 online ahead printabstractintroduction rapid development electromechanical robotic devices profoundly influenced neurorehabilitation growth scientific technological aspects thereof crucial increasing number newly developed devices clinicians welcomed growth enthusiasm nevertheless improving standard reporting clinical technical normative aspects electromechanical robotic devices remains unmet need neurorehabilitation accordingly study aimed analyse existing literature electromechanical robotic devices used neurorehabilitation considering current clinical technical regulatory classification systemsevidence acquisition within cicerone consensus conference framework studies electromechanical robotic devices used upper lowerlimb rehabilitation persons neurological disabilities adulthood childhood reviewed conducted literature search using following databases medline cochrane library pedro institute electrical electronics engineers science direct google scholar clinical technical regulatory classification systems applied collect information electromechanical robotic devices study designs populations investigatedevidence synthesis overall 316 studies included analysis half 52 studies randomised controlled trials rcts population investigated suffered strokes followed spinal cord injuries multiple sclerosis cerebral palsy traumatic brain injuries total 100 devices described 19 certified ce mark overall main type device exoskeleton however endeffector devices primarily used upper limbs whereas exoskeletons used lower limbs children adults conclusions current literature robotic neurorehabilitation lacks detailed information regarding technical characteristics devices used affects understanding possible mechanisms underlying recovery unfortunately many electromechanical robotic devices provided ce marks strongly hindering research clinical outcomes rehabilitation treatments based devices significant effort needed improve description robotic devices used neurorehabilitation terms technical functional details along highquality rct studiespmid34042413 doi1023736 s1973908721069227,0.0
impact covid19 pandemic access health care services among patients multiple sclerosis lazio region italy eur j neurol 2021 apr 25 doi 101111 ene14879 online ahead printabstractbackground multiple sclerosis ms complex chronic autoimmuneinflammatory disease involving multidisciplinary assessments interventions explored access outpatient specialist home health care services pandemic outbreak lockdown among ms patients lazio region also described adherence disease modifying therapies dmts methods populationbased study conducted using regional health care administrative databases validated algorithm used identify ms cases period 20112018 compared number specialist homebased services 2019 2020 medication possession ratio mpr used measure adherence dmtresults total 9380 ms patients identified 68 women observed decline number outpatient care services march june 2020 compared previous year particular rehabilitation 82 magnetic resonance 56 neurological specialist services 91 important year year variations observed may june 2020 homebased nursing medical care 91 motor reeducation services 74 adherence dmts higher first four months 2019 compared period 2020 671 vs 570 conclusions observed notable disruption rehabilitative therapy homebased services well dmt adherence since pandemic still ongoing interruption health care services major impact ms patients necessary monitor access ms patients healthcare resources order ensure adequate treatments including rehabilitative therapiespmid33896086 doi101111 ene14879,0.0
choroid plexus enlargement inflammatory multiple sclerosis 30t mri translocator protein pet evaluation radiology 2021 jul 13204426 doi 101148 radiol2021204426 online ahead printabstractbackground choroid plexuses cps suggested key gateway inflammation experimental autoimmune encephalitis vivo evidence involvement multiple sclerosis ms lacking purpose assess cp volumetric inflammatory changes patients ms versus healthy control participants materials methods secondary analysis 97 patients 61 relapsingremitting ms rrms 36 progressive ms 44 healthy control participants participated three prospective 30t brain mri studies may 2009 september 2017 subgroup 37 patients 19 healthy control participants also underwent translocator protein fluorine 18 18f dpa714 pet neuroinflammation relapses disability scores collected baseline 2 years cps manually segmented threedimensional t1weighted images brain volumes additionally segmented volumes expressed ratio intracranial volume 18fdpa714 distribution volume ratio quantified parenchymal regions whereas standardized uptake value used cp inflammation multivariable linear regression analyses performed assess cp volumetric inflammatory differences patients ms healthy control participants correlations cp volume lesion load brain volumes 18fdpa714 uptake annualized relapse rate results ninetyseven patients ms mean age 42 years 12 standard deviation 49 women 44 healthy control participants mean age 39 years 14 23 women underwent mri thirtyseven patients ms 19 healthy control participants underwent pet cps 35 larger patients ms mean value 159 104 45 healthy control participants mean value 118 104 38 p 004 subgroup analysis confirmed greater cp volume patients rrms mean value 155 104 46 p 008 healthy control participants cp enlargement greater patients active lesions mri mean volume 182 104 49 patients lesions enhanced gadolinium vs 149 104 4 patients lesions enhance gadolinium p 001 correlated white matter lesion load r 039 95 ci 020 055 p 001 18fdpa714 binding thalami r 044 95 ci 022 072 p 04 normalappearing white matter r 05 95 ci 020 071 p 005 moreover correlated annualized relapse rate patients rrms r 037 95 ci 01 055 p 005 finally patients ms showed 185 higher cp 18fdpa714 uptake control participants mean value 0778 023 vs 0635 015 respectively p 01 cp volume patients rrms r 057 95 ci 037 073 p 009 correlated higher 18fdpa714 uptake conclusion choroid plexuses cps enlarged inflamed patients multiple sclerosis ms particularly relapsingremitting ms inflammatory profiles cp volumetric analysis represent ms imaging marker rsna 2021 eudract 200800417440 clinical trial registration nos nct02305264 nct01651520 online supplemental material available articlepmid34254858 doi101148 radiol2021204426,0.0
postpartum relapse women multiple sclerosis neuraxial labour analgesia neuraxial anaesthesia multicentre retrospective cohort study anaesth crit care pain med 2021 mar 19100834 doi 101016 jaccpm2021100834 online ahead printabstractbackground proportion women multiple sclerosis experiencing relapse postpartum period neuraxial labour analgesia neuraxial anaesthesia remains uncertain study aimed assess association neuraxial labour analgesia neuraxial anaesthesia occurrence relapse first three months postpartummethods retrospective cohort study cases women diagnosis multiple sclerosis delivering january 2010 april 2015 analysed demographic anaesthetic obstetric characteristics occurrence number relapses year preceding pregnancy pregnancy first three postpartum months recorded logistic regression analyses performed identification factors associated occurrence postpartum relapseresults total 118 deliveries 104 parturients included 78 66 vaginal deliveries 40 34 caesarean deliveries neuraxial analgesia provided 50 deliveries neuraxial anaesthesia 46 deliveries neuraxial anaesthesia analgesia administered remaining 22 deliveries postpartum relapse occurred 31 women 26 association obstetric anaesthetic characteristics postpartum relapse occurrence number relapses prior pregnancy time last relapse delivery significantly associated postpartum relapse univariate analysis occurrence relapse within year preceding pregnancy sole independent factor associated postpartum relapseconclusion neuraxial procedures associated increased rate postpartum relapse disease activity prior pregnancy predictive postpartum relapsepmid33753296 doi101016 jaccpm2021100834,0.0
complementassociated loss ca2 inhibitory synapses demyelinated hippocampus impairs memory acta neuropathol 2021 jun 25 doi 101007 s00401021023388 online ahead printabstractthe complement system implicated synapse loss ms hippocampus functional consequences synapse loss remain poorly understood postmortem ms hippocampi demyelination find deposits complement component c1q enriched ca2 subfield linked loss inhibitory synapses significantly higher ms patients cognitive impairments compared preserved cognitive functions using cuprizone mouse model demyelination corroborated c1q deposits highest within demyelinated dorsal hippocampal ca2 pyramidal layer colocalized inhibitory synapses engulfed microglia macrophages agreement loss inhibitory perisomatic synapses found schaffer collateral feedforward inhibition excitation impaired ca2 pyramidal neurons accompanied intrinsic changes reduced spike output finally consistent excitability deficits show cuprizonetreated mice exhibit impaired encoding social memories together findings identify ca2 critical circuit demyelinated intrahippocampal lesions memory dysfunctions mspmid34170374 doi101007 s00401021023388,1.0
emerging roles coronavirus autoimmune diseases arch med res 2021 apr 8s01884409 21 000837 doi 101016 jarcmed202103012 online ahead printabstractvirus infection can alter immune regulatory activity thus may involved occurrence autoimmune diseases recently pandemic covid19 posed huge threat public health emerging evidence suggests coronavirus may implicated development pathogenesis autoimmune diseases however coronavirus infection impacts risk autoimmune disease remains largely unknown review focused association coronavirus autoimmunity elucidated molecular mechanisms linking coronavirus exposure autoimmunity additionally briefly introduced role coronavirus plays several autoimmune diseases including multiple sclerosis ms rheumatoid arthritis ra systemic lupus erythematosus sle idiopathicthrombocytopenic purpura itp pmid33875273 doi101016 jarcmed202103012,0.0
evidence tell us use gait robotic devices patients multiple sclerosis comprehensive systematic review functional outcomes clinical recommendations eur j phys rehabil med 2021 sep 22 doi 1023736 s197390872106915x online ahead printabstractintroduction growing evidence efficacy gait robotic rehabilitation patients multiple sclerosis ms studies focused gait parameters moreover clear indications clinical use robotics still lack part cicerone italian consensus robotic rehabilitation aim systematic review investigate existing evidence concerning role lower limb robotic rehabilitation improving functional recovery patients msevidence acquisition searched systematically reviewed evidencebased studies gait robotic rehabilitation ms january 1st 2010 december 31st 2020 following databases cochrane library pedro pubmed google scholar study quality assessed 16item assessment multiple systematic reviews 2 amstar 2 10item pedro scale research studiesevidence synthesis accurate screening 17 papers included review 13 rct level ii evidence studies used lokomat grounded robotic device two investigated efficacy endeffectors two powered exoskeletons generally speaking robotic treatment beneficial effects gait speed endurance balance comparable outcomes conventional treatments however severe patients edss 6 robotics leads better functional outcomes notably gait training robotics especially coupled virtual reality ms patients also reach better nonmotor outcomes including spasticity fatigue pain psychological wellbeing quality life unfortunately clinical indications emerge treatment protocolsconclusions present comprehensive systematic review highlights potential beneficial role functional outcomes lower limb robotic devices people ms future studies warranted evaluate role robotics walking balance outcomes also gaittrainingrelated benefits identify appropriate outcome measures related specific subgroup ms subjects disease severitypmid34547886 doi1023736 s197390872106915x,0.0
autoimmune encephalitis retrospective monocentric experience mult scler relat disord 2021 aug 6 55103191 doi 101016 jmsard2021103191 online ahead printno abstractpmid34388533 doi101016 jmsard2021103191,0.0
role sphingosine1phosphate mediated signalling systemic lupus erythematosus prostaglandins lipid mediat 2021 aug 2106584 doi 101016 jprostaglandins2021106584 online ahead printabstractsystemic lupus erythematosus sle highly prevalent autoimmune disease characterized malfunction immune system persistent presence inflammatory environment multiple organs can affected sle leading heterogeneous manifestations eventually result death patients due lack understanding regarding pathogenesis sle currently available treatments remain suboptimal sphingosine1phosphate s1p central bioactive lipid sphingolipid metabolism serves pivotal role regulating numerous physiological pathological processes wellrecognized regulator lymphocyte trafficking s1p shown closely associated autoimmune diseases including sle importantly s1p levels found elevated patients sle murine models lupus increased levels s1p also contribute disease activity organ impairment moreover data several studies also support hypothesis s1p receptors producersphingosine kinases sphk may serve potential targets treatment sle comorbidities given significant success intervening s1p signaling achieved treating multiple sclerosis exploration role sle necessary therefore aim present review summarize recent advances understanding potential mechanism s1p influences sle primary focus role immune regulation inflammatory responsespmid34352381 doi101016 jprostaglandins2021106584,0.0
understanding abnormal cjnk p38mapk signaling overactivation involved progression multiple sclerosis possible therapeutic targets impact neurodegenerative diseases neurotox res 2021 aug 25 doi 101007 s12640021004016 online ahead printabstractdemyelination immune dysregulation neuroinflammation common triggers motor neuron disorders multiple sclerosis ms ms chronic demyelinating neurodegenerative disease central nervous system caused abnormal immune activation causes myelin sheath damage cell signal transduction pathways required variety physiological pathological processes brain signaling systems become overactive can lead disease progression various physiological conditions abnormal mitogenactivated protein kinase mapk activation associated several physiological dysfunctions cause neurodegeneration previous research indicates cjnk p38mapk signaling play critical roles neuronal growth differentiation cjnk p38mapk member mapk family regulates metabolic pathways cell proliferation differentiation apoptosis control certain neurological activities brain injuries cjnk p38mapk also affects neuronal elastic properties nerve growth cognitive processing review systematically linked abnormal cjnk p38mapk signaling activation multiple neuropathological pathways ms related neurological dysfunctions ms progression linked genetic defects oligodendrocyte destruction glial overactivation immune dysregulation concluded inhibiting cjnk p38mapk signaling pathways can promote neuroprotection neurotrophic effects clinicalpathological presentation ms influence neurological disorders result potential benefits cjnk p38mapk downregulation development diseasemodifying treatment interventions future include ms prevention related neurocomplicationspmid34432262 doi101007 s12640021004016,1.0
protective features calorie restriction cuprizoneinduced demyelination via modulating microglial phenotype j chem neuroanat 2021 aug 12102013 doi 101016 jjchemneu2021102013 online ahead printabstractmultiple sclerosis ms immunemediated demyelinating disorder central nervous system cns definitive treatment can alleviated changing life habits calorie restriction cr effective preventing treating metabolic autoimmune disorders cr one helpful approaches control progression ms present study investigated preventive effect caloric restriction cuprizone induceddemyelination model multiple sclerosis induce acute demyelination c57 bl6 mice added 02 cuprizone cpz diet 6 weeks induce calorie restriction 10 carboxymethyl cellulose cmc added diet dietary cellulose fiber 6 weeks remyelination studied luxol fast blue lfb staining microglia activity m1 m2 microglial macrophage phenotypes assessed immunohistochemistry iba1 inos arg1 respectively expression targeted genes assessed realtime polymerase chain reaction luxol fast blue lfb staining showed cr regimen decrease cuprizoneinduced demyelination process p 001 moreover cr application improve balance motor performance cuprizoneintoxicated mice significantly enhancing protein gene expression sirt1 m2 microglial phenotype marker arg1 akt1 gene expression also decreased m1 microglial phenotype marker inos akt2 p53 gene expressions p 005 cumulatively can concluded caloric restriction able counteract ms symptoms alleviating inflammatory responsespmid34391881 doi101016 jjchemneu2021102013,1.0
comorbidities require special attention minorities multiple sclerosis mult scler 2021 aug 2713524585211037578 doi 101177 13524585211037578 online ahead printno abstractpmid34449300 doi101177 13524585211037578,0.0
chickenpox asymptomatic covid19 first cycle alemtuzumab multiple sclerosis neurol sci 2021 jul 31 doi 101007 s10072021054956 online ahead printno abstractpmid34331616 doi101007 s10072021054956,0.0
epilepsy heterogeneous earlylife tuberous sclerosis complex pediatr neurol 2021 jul 6 12319 doi 101016 jpediatrneurol202106012 online ahead printabstractbackground epilepsy tuberous sclerosis complex tsc typically presents early onset multiple seizure types intractability however variability observed among individuals detailed individual data seizure characteristics collected prospectively early life used define epilepsy profiles populationmethods children aged zero 36 months followed longitudinally caregivers kept daily seizure diaries including onset daily counts seizure type patients 70 seizure diary completion 365 diary days included developmental outcomes 36 months compared subgroupsresults epilepsy seen 124 156 79 participants seizure onset occurred zero 295 months 93 onset age 12 months focal seizures epileptic spasms common number seizures median 897 days ranged 1 9128 hierarchical clustering based six metrics seizure burden age onset total seizures ratio seizure days nonseizure days seizures per seizure day worst seven 30day stretches revealed two distinct groups broadly favorable unfavorable epilepsy profiles subpopulations within group showed clinically meaningful differences seizure burden groups higher seizure burden worse developmental outcomes 36 monthsconclusions although epilepsy highly prevalent tsc young children tsc epilepsy profile least two phenotypic subpopulations discernible based seizure burden early aggressive treatments epilepsy tsc may best leveraged targeting specific subgroups based phenotype severitypmid34343869 doi101016 jpediatrneurol202106012,0.0
utilization multiple sclerosis therapies middle east decade 20092018 cns drugs 2021 jun 23 doi 101007 s4026302100833w online ahead printabstractbackground multiple sclerosis ms landscape changed past two decades across world middle east middle east ethnically diverse region located 12 42 latitude 35 54 longitude varying altitudes magnitude shifts observed epidemiology management ms differ region country countryobjectives aim study provide clinicodemographic overview cohorts patients contributed msbase large international ms registry middle east describe diseasemodifying treatment dmt utilization different countries within region understanding differences cohorts integral interpretation studies conducted using registry data provides insight clinical practice cohortsmethods msbase registry searched patients ms clinically isolated syndrome middle eastern countries data captured 2009 2018 2year epochs special focus recent epoch 20172018 explored demographic clinical characteristics treatment exposures studied cohorts reported results using standard descriptive statisticsresults 10year study period 13 356 patients 17 centers 8 middle eastern countries fulfilled inclusion criteria represented countries egypt iran kuwait lebanon oman saudi arabia turkey united arab emirates overall represented cohort young median 36 years quartiles 2945 captured relatively early onset ms median disease duration 10 years quartiles 312 relapsingremitting phenotype prevalent phenotype countries 7397 highest proportion progressive ms reported saudi arabia 12 median expanded disability status scale edss ranged 0 3 depicting mildly disabled cohort exception saudi arabia median edss 4 quartiles 1565 median relapse frequency highest lebanon median 103 95 ci 094116 followed egypt median 102 95 ci 089124 lowest saudi arabia median 070 95 ci 058095 kuwait median 075 95 ci 071080 treatment landscape greatly varied different countries platform injectable therapies mostly utilized egypt iran turkey 86 79 53 respectively oral therapies monoclonal antibodies commonly used kuwait lebanon united arab emirates 872 673 587 respectively conclusion patients middle east enrolled large multinational registry representative general ms population spectrum therapies used individual countries however highly variable studies include rural nonacademic practices needed enhance understanding ms cohorts middle eastpmid34164782 doi101007 s4026302100833w,0.0
disease activity prior fingolimod initiation predictive response fingolimod common first line treatment rev neurol paris 2021 feb 23s00353787 21 000400 doi 101016 jneurol202011009 online ahead printabstractbackground countries fingolimod available firstline therapy without restrictions opportunity observe longterm efficacy profile drug treatmentnaive patients according initial disease activitymethods retrospectively analysed data rrms patients treated fty focusing 2 groups 17 highly active patients ha defined follows 2 relapses year treatment initiation either1 gdenhancing t1 lesion significant increase t2 lesion load baseline mri 37 highly active nha reviewed treatment efficacy defined neda3 reasons discontinuation treatment tolerance groupsresults mean followup duration 482 months sd 184 fingolimod efficiently reduced relapses nha 903 reduction p0001 ha 849 p0001 new gd enhancing lesions nha 854 reduction p0019 ha 923 p0043 proportion patients reaching neda3 status higher nha group nha 80 2 years 66 4 years ha 58 2 years 38 4 years p0042 fingolimod discontinued 20 cases mainly lack efficacy n15 conclusions fty efficient reducing relapses new gd enhancing lesions ha nha patients although probability achieving neda3 time higher earlytreated treatmentnaive nha patientspmid33637293 doi101016 jneurol202011009,0.0
infections multiple sclerosis recommendations french multiple sclerosis society rev neurol paris 2021 jul 21s00353787 21 006020 doi 101016 jneurol202104011 online ahead printabstractintroduction viral bacterial fungal infections suspected triggering multiple sclerosis ms promoting relapses disease likely promoted immuneactive treatments raises questions infectious workup preventive treatment infections prior initiationobjectives establish recommendations infections ms provide information patients healthcare professionals minimal infectious workup performed ms patient diagnosis prior initiation immunoactive therapy msmethods recommendation attempts answer four main questions infections ms french group recommendations multiple sclerosis france4ms systematic review articles pubmed universities databases january 1975 june 2020 using rand ucla formalized consensus method rand ucla method developed synthesize scientific literature expert opinions health care topics used reaching formal agreement twentythree experts contributed detailed review group 63 multidisciplinary health professionals validated final version 36 recommendationsresults recommended ms patients undergo minimal infectious workup check vaccination status diagnosis repeat followup starting immunotherapy screening preventive treatment viral group herpes virus hpv jcv hcv hbv bacterial mycobacteria fungal cryptococcus infections recommended prior initiation certain immunoactive ms therapiesdiscussion conclusions diagnosis ms prior choice therapeutic strategy recommended update vaccination schedule ms patients reference hcsp vaccination schedule sfsep recommendations starting immunosuppressive treatment recommended inform patients risks infections look constitutive acquired immune deficiency health professionals patients informed updated recommendations infections mspmid34303537 doi101016 jneurol202104011,0.0
influenza vaccination status multiple sclerosis patients latin america j neurovirol 2021 sep 29 doi 101007 s1336502101011w online ahead printabstractthe objective present study identify frequency ms patients latin america latam received influenza vaccine recent season reasons related nonvaccination crosssectional study november december 2020 large cohort ms patients latam patients responded recommendation receiving influenza vaccine use well reasons using vaccine four hundred twelve ms patients included analysis 473 patients recommended receive vaccine treating physician nearly 54 patients receive influenza vaccine frequent cause neither recommended mentioned treating physician 274 female gender 23 95ci 1438 p 0001 associated increased risk recommendation progressive form ms higher edss decreased risk 049 95ci 027090 p 0023 065 95ci 055097 p 002 respectively despite evidence recommend influenza vaccine ms patients limited number patients clinical practice received recommendationpmid34586604 doi101007 s1336502101011w,0.0
oncologic causes oculopalatal tremors neurophysiology treatment acta neurol belg 2021 jul 20 doi 101007 s13760021017618 online ahead printabstractoculopalatal tremor opt acquired pathology characterized continuous rhythmical soft palatal movements combined pendular nystagmus aside vascular lesions oncological masses affecting dentatorubroolivary pathway can impair brainstem cerebellar pathways manifesting dyssynchronous movement review delve neurophysiology opt along oncological causes treatment options based recent clinical trial data literature review includes medication treatment data clinical trials enrolling individuals features opt including acquired pendular nystagmus apn trials deemed eligible inclusion review one participants symptoms determined trial authors caused opt trials investigating treatment apn secondary separate cause multiple sclerosis excluded review several early treatments failed demonstrate benefit patients apn due opt trials anticholinergic agents largely ineffective poorly tolerated botulinum toxin demonstrated improvement apn symptoms recently trials including memantine gabapentin demonstrated success attenuation apn surgical modalities dbs yet show improvement though single case report evidence oculopalatal tremor unique manifestation posterior fossa tumors disrupting guillainmollaret triangle symptom control medication management limited success attributed poor response medication intolerance surgical modalities like dbs may emerging role opt treatment targeting dyssynchronous activity dentatorubroolivary pathwaypmid34286476 doi101007 s13760021017618,0.0
consumer experience flexible exercise participation program fepp individuals multiple sclerosis mixedmethods study physiother res int 2021 sep 28e1922 doi 101002 pri1922 online ahead printabstractbackground purpose flexible exercise participation program fepp novel intervention developed enable individuals multiple sclerosis ms participate progress exercise sport choice fepp underpinned guidelines aerobic exercise individuals ms supported physiotherapist using behaviour change techniques part fepp feasibility trial aim nested study explore experience participation fepp perspective individuals ms objectives determine acceptability fepp ii identify recommendations improvementmethods mixed methods study using sequential explanatory design conducted part consisted quantitative participant survey survey data analysed descriptively using spss informed protocol part ii qualitative interviews interview data analysed thematically using nvivo part iii consisted integration quantitative qualitative data allow greater explanation survey responses individuals ms participated fepp feasibility trial invited take part studyresults fepp highly acceptability 10 participants five themes emerged describe experience participating fepp exploring exercise boundaries ii measuring energy iii acknowledging accountability iv adjusting exercising pandemic v sustaining participation recommendations improving fepp included changes energy level monitoring incorporation peer support mechanismsdiscussion participants found fepp highly acceptable valued flexibility choose activity health professional support based participant recommendations future versions fepp will include daily rather weekly monitoring exercise peer support enable individuals ms find right balance exercise sportpmid34585470 doi101002 pri1922,0.0
dna methylation regulates expression negative transcriptional regulators id2 id4 opc differentiation cell mol life sci 2021 sep 5 doi 101007 s00018021039272 online ahead printabstractthe differentiation oligodendrocyte precursor cells opcs myelinating oligodendrocytes prerequisite remyelination demyelinated disorders multiple sclerosis ms epigenetic mechanisms dna methylation suggested control intricate network transcription factors involved opc differentiation yet exact mechanism remains undisclosed first identify dnabinding protein inhibitors id2 id4 targets dna methylation opc differentiation using stateoftheart epigenetic editing via crispr dcas9dnmt3a confirm targeted methylation id2 id4 drives opc differentiation moreover show pathological context ms methylation gene expression levels id2 id4 altered compared control human brain samples conclude dna methylation crucial suppress id2 id4 opc differentiation process appears dysregulated ms data reveal new insights oligodendrocyte biology also lead better understanding cns myelin disorderspmid34482420 doi101007 s00018021039272,1.0
update infective complications patients treated alemtuzumab multiple sclerosis review metaanalysis realworld randomized studies expert opin drug saf 2021 jul 26110 doi 101080 1474033820211942454 online ahead printabstractobjective aimed systematically assess pooled prevalence infective complications randomized controlled trials rcts realworld studies rwss investigating alemtuzumab treatment multiple sclerosis ms also looking selected infections severitymethods included analysis rcts rwss investigating use alemtuzumab ms infective complications reported well case reports rare infections conducted metaanalysis proportions random effect model metaregression investigate heterogeneityresults pooled prevalence infective complications alemtuzumab treated ms patients 24 common reported infections respiratory tract infections 47 part infections mildtomoderate 85 severe infections account 6 total estimate found firsttimereported cases invasive aspergillosis hepatitis e virus infection ebv hepatitis cerebral toxoplasmosis prevalence infections higher studies conducted 2009 studies higher proportion male participantsconclusions clinicians aware prevalence serious infections alemtuzumab can higher expected rcts peculiar opportunistic infections considered evaluating patient treated alemtuzumab develops signs infectionpmid34310251 doi101080 1474033820211942454,0.0
research progress opioid growth factor immunerelated diseases cancer diseases int immunopharmacol 2021 aug 10 99107713 doi 101016 jintimp2021107713 online ahead printabstractmethionine enkephalin menk important role neuroendocrine immune systems menk known opioid growth factor ogf growth regulatory characteristics ogf interacts ogf receptor ogfr inhibit dna synthesis upregulating p16 p21 delays cell cycle transition g0 g1 s phase inhibits cell proliferation addition ogf combines ogfr immune cells exert immunomodulatory activity regulate immune function ogf studied immunomodulator variety autoimmune diseases including multiple sclerosis inflammatory bowel disease diabetes viral infections proven relieve symptoms certain diseases animal vitro experiments also ogf ogfr various antitumor molecular mechanisms ogf can used primary therapy alone combined drugs treat tumors article summarizes research progress ogf immunerelated diseases cancer diseasespmid34426103 doi101016 jintimp2021107713,0.0
tuberous sclerosis complex misdiagnosed multiple metastases cervical cancer patient case report literature review ann palliat med 2021 jan 10 10 1123211238 doi 1021037 apm212814abstracttuberous sclerosis complex tsc autosomal dominant disorder affects multiple organs caused inactive mutations tsc1 tsc2 genes main symptoms tsc neurocutaneous syndrome benign hamartoma formation notably malignancy indication tsc article present case 48yearold female cervical cancer cc combined tsc misdiagnosed multiple metastases toe masses pelvic nodules multiple osteogenic lesions initially observed multisite puncture biopsies toe amputation performed pathology results indicate malignancy subsequently hypomelanotic macules back subependymal nodules sens ungual fibromas multiple renal cysts scleroticbonelesions sbls skull vertebrae observed leading diagnosis tsc given tsc benign disease yet caused organ disfunction special treatment provided patient followup period almost 65 months patients quality life remained good without therapy oncologists pay attention benign diseases face multiple lesions reduce misdiagnosis overtreatment addition tsc may interact cc molecular mechanisms mammalian target rapamycin mtor pathwaypmid34763482 doi1021037 apm212814,0.0
efficient roles mir146a cellular molecular mechanisms neuroinflammatory disorders effectual review neuroimmunology immunol lett 2021 jul 19s01652478 21 001139 doi 101016 jimlet202107004 online ahead printabstractknown one sophisticated systems human body nervous system consists neural cells controls parts body closely related immune system effects inflammation immune reactions observed pathogenesis neurological disorders defined gene expression regulators mirnas participate cellular processes mir146a mediator neuroimmune system leaving substantial effects homeostasis immune brain cells neuronal identities acquisition immune responses regulation nervous system positive efficiency proven modulating inflammatory reactions hemorrhagic complications pain moreover mir146a targets play key role pathogenesis illnesses based performance targets mir146a can various effects disease progress abnormal expression function mir146a reported neuroinflammatory disorders research evidence molecule qualifies desirable biomarker disorders can even therapeutic target study aims provide meticulous review regarding roles mir146a pathogenesis progression several neuroinflammatory disorders multiple sclerosis amyotrophic lateral sclerosis alzheimers disease temporal lobe epilepsy ischemic stroke etc study also considers eligibility use ideal biomarker therapeutic target diseases awareness mechanisms can facilitate disease management treatment lead patients amelioration improve quality life mitigate risk deathpmid34293378 doi101016 jimlet202107004,0.0
aerobic resistance training effective exercise modality improving lower extremity physical function perceived fatigue people multiple sclerosis systematic review metaanalysis arch phys med rehabil 2021 apr 23s00039993 21 003075 doi 101016 japmr202103026 online ahead printabstractobjective purpose systematic review investigate whether aerobic training resistance training rt effective terms improving lower limb physical function perceived fatigue persons multiple sclerosis pwms data sources nine databases medline embase cinahl amed pedro sportdiscus psycinfo web science scopus electronically searched april 2020study selection included studies randomized controlled trials rcts involving pwms attending one two exercise interventions rt studies include least one objective selfreported outcome lower extremity physical function perceived fatiguedata extraction data extracted using customized spreadsheet included detailed information patient characteristics interventions outcomes methodological quality included studies independently assessed two reviewers using testex rating scaledata synthesis twentyseven papers reporting data 22 rcts at14 rt8 including 966 pwms two modalities found equally effective terms improving short walk test es033 149 206 rt es027 007 047 long walk test performance es037 004 078 rt es036 035 108 well reducing perceived fatigue es061 110011 rt es041 080 002 findings functional mobility tests along selfreported walking performance sparse inconclusiveconclusions rt appear equally highly effective terms improving lower extremity physical function perceived fatigue pwms clinicians can thus use either modality target impairments outcomes future perspective headtohead exercise modality studies warranted future ms exercise studies encouraged adapt consensus core battery physical function tests facilitate detailed comparison results across modalitiespmid33901439 doi101016 japmr202103026,0.0
prevalence antineurofascin155 antibodies patients neuromyelitis optica spectrum disorders clin exp immunol 2021 may 17 doi 101111 cei13617 online ahead printabstractbackground antineurofascin155 nf155 antibodies observed two cases neuromyelitis optica spectrum disorders nmosd study investigated prevalence antinf155 antibodies patients nmosd clinical features antinf155 antibodypositive patientsmethods sera 129 patients nmosd screened antinf155 antibodies cellbased assay cba reexamined using immunostaining mouse teased sciatic nerve fibers fiftysix patients multiple sclerosis ms 50 healthy controls hc also enrolled detecting antinf155 antibodiesresults 1240 16 129 patients nmosd positive antinf155 antibodies confirmed cba immunostaining igg1 predominant subclass however none 56 ms patients 50 hc positive antinf155 antibodies antinf155 antibodypositive nmosd patients higher proportion coexisting autoimmune diseases p 0001 higher positive rates serum nonorganspecific autoantibodies including antissa antibodies p 0001 antissb antibodies p 0008 antiro52 antibodies p 0001 rheumatoid factor p 0001 five antinf155 antibodypositive nmosd patients performed nerve conduction study showed mildly abnormal results differences nerve conduction study parameters observed antinf155 antibodypositive negative patientsconclusion antinf155 antibodies occurred small proportion nmosd patients antinf155 antibodypositive nmosd patients tended coexist autoimmune diseasespmid33998675 doi101111 cei13617,0.0
factors affecting risk relapsingonset progressiveonset multiple sclerosis j neurol neurosurg psychiatry 2021 may 13jnnp2020325688 doi 101136 jnnp2020325688 online ahead printabstractobjective debated whether different clinical disease courses multiple sclerosis ms consequence different pathogenic mechanisms distinct risk factors ms clinical phenotypes variations similar underlying disease mechanisms aimed study environmental risk factors interactions human leucocyte antigen drb11501 regards relapsingonset progressiveonset msmethods used two swedish populationbased casecontrol studies including 7520 relapsingonset cases 540 progressiveonset cases 11 386 controls matched age sex residential area logistic regression used estimate ors 95 cis associations different ms phenotypes number environmental lifestyle factors interaction drb11501 allele environmental risk factors evaluated additive scaleresults environmental lifestyle factors associated risk developing ms apply relapsingonset progressiveonset disease smoking obesity epsteinbarr virus nuclear antigen1 ebna1 antibody levels associated increased risk ms phenotypes whereas snuff use alcohol consumption sun exposure associated reduced risk additive interactions drb11501 smoking obesity ebna1 antibody levels sun exposure respectively occurred increase ms risk regardless clinical phenotypeinterpretation finding environmental lifestyle factors affect relapsingonset progressiveonset ms supports notion different clinical phenotypes share common underlying disease mechanismspmid33986119 doi101136 jnnp2020325688,0.0
7t mri differetiates remyelinated demyelinated multiple sclerosis lesions ann neurol 2021 aug 14 doi 101002 ana26194 online ahead printabstractobjective noninvasively assess myelin status chronic white matter lesions multiple sclerosis ms developed evaluated simple classification scheme based t1 relaxation time maps derived 7tesla postmortem vivo mrimethods using mp2rage mri sequence classified 36 lesions 4 postmortem ms brains longt1 shortt1 mixedt1 visual comparison neocortex within groups compared t1 times histologically derived measures myelin axons performed similar analysis 235 chronic lesions known date onset 25 ms cases vivo validation cohort 222 lesions 66 ms cases investigating associations clinical radiological outcomesresults postmortem lesions classified qualitatively longt1 shortt1 mixedt1 corresponded fully demyelinated fully remyelinated mixed demyelinated remyelinated lesions respectively p 0001 demyelination rather axon loss dominantly contributed initial t1 prolongation observed lesions similar characteristics vivo allowing manual classification substantial interrater excellent intrarater reliability shortt1 lesions common deep white matter whereas longt1 mixedt1 lesions prevalent juxtacortical periventricular white matter p 002 much likely paramagnetic rims suggesting chronic inflammation p 0001 older age time lesion formation portended less remyelination p 0007 interpretation 7tesla t1 mapping mp2rage clinically available mri method allows qualitative quantitative classification chronic ms lesions according myelin content rendering straightforward tracking lesional myelination changes time article protected copyright rights reservedpmid34390015 doi101002 ana26194,1.0
inhibition nacylethanolaminehydrolyzing acid amidase reduces tcell infiltration mouse model multiple sclerosis pharmacol res 2021 aug 12105816 doi 101016 jphrs2021105816 online ahead printabstractexperimental autoimmune encephalomyelitis eae animal model multiple sclerosis ms myeloid cells sustain inflammation take part priming differentiation reactivation myelinspecific tcells cause direct myelin damage nacylethanolaminehydrolyzing acid amidase naaa proinflammatory enzyme induced phlogosis overexpressed macrophages microglia eae mice targeting cell populations inhibiting naaa may promising pharmacological strategy modulate inflammatory aspect ms manage disease progression address goal used arn16186 small molecule specifically designed synthesized pharmacological tool inhibit naaa assessed whether enzyme inhibition affected severity neurological symptoms modulated immune cell infiltration central nervous system eae mice found preventive chronic treatment arn16186 efficacious slowing disease progression preserving locomotor activity eae mice furthermore naaa inhibition reduced number immune cells infiltrating spinal cord modulated overactivation nfkb stat3 transcription factors leading less expansion th17 cells course diseasepmid34391933 doi101016 jphrs2021105816,1.0
comparative assessment proliferation immunomodulatory potential hypericum perforatum plant callus extracts mesenchymal stem cells derived adipose tissue multiple sclerosis patients inflammopharmacology 2021 sep 12 doi 101007 s10787021008383 online ahead printabstractbackground mesenchymal stem cellsderived adipose tissue atmscs recognized treatment inflammatory diseases including multiple sclerosis ms hypericum perforatum hp antiinflammatory pharmaceutical plant bioactive compounds plant tissue culture technique improve desired pharmacological potential aim study compare antiinflammatory proliferative effects callus fieldgrowing plant extracts hp atmscs derived ms patientsmaterials methods atmscs isolated characterized hp callus prepared exposure light spectrum blue red bluered control total phenols flavonoids hypericin hp callus plant extracts measured effects hp extracts concentrations proliferation evaluated mtt assay coculture atmscs pbmcs challenged hp plant callus extracts tregs percentage assessed flow cytometryresults identification mscs performed data showed blue light stimulate total phenols flavonoids hypericin mtt test demonstrated plant extract concentrations 003 12 25 10 g ml hp callus extract 10 g ml significantly increased hp extracts lead increase tregs percentage concentrations particular comparison hp plant callus extracts revealed tregs enhanced 3fold control groups concentration 10 g ml callusconclusions high concentrations hp extracts showed effectiveness atmscs proliferation immunomodulatory properties certain consequence callus extract hp extracts may considered supplementary treatments patients receiving mscs transplantationpmid34510276 doi101007 s10787021008383,0.0
effect visual field manipulations standing balance control people multiple sclerosis gait posture 2021 aug 14 909298 doi 101016 jgaitpost202108010 online ahead printabstractbackground multiple sclerosis ms associated increased risk falls degeneration sensory organization possible increased reliance vision balance controlresearch question aim study assess differences standing postural control people ms age sex matched controls mediallateral ml oscillations visual field without blinders lower peripherymethods ten persons ms mean age 540 53 years ten age sex matched controls mean age 563 60 years participated study balance control assessed participants stood christie cave system wearing stereoscopic glasses projected immersive forest scene visual conditions consisted 2 m ml visual oscillations scene five frequencies 00 03 06 07 08 hz without blinders block lower peripheryresults significance results demonstrated comparison controls participants ms significantly larger center pressure sway ml ap direction ml visual oscillations additionally participants ms controls increased center pressure frequency content visual oscillation frequency participants ms also increased relative power visual oscillation frequency ap direction blinders lower periphery reduced percent power visual oscillation frequency groups reduced overall sway participants ms visual oscillations overall results indicate postural balance sensitive visual feedback people ms elicited ap sway ml visual oscillation reflect errors visual processing control balance decreased sway response blocking vision lower peripheral field indicate increased reliance visual cues maintain balancepmid34419916 doi101016 jgaitpost202108010,0.0
efficacy probiotics experimental autoimmune encephalomyelitis animal model ms systematic review metaanalysis#39 lett appl microbiol 2021 jul 26 doi 101111 lam13543 online ahead printabstractprobiotics immunomodulatory properties beneficial effects diseases multiple sclerosis ms reported several studies current systematic review metaanalysis aimed investigate favourable effects probiotics improving experimental autoimmune allergic encephalomyelitis eae animal model ms systematically searched scopus web sciences isi pubmed databases identify relevant studies inception databases december 2019 total 15 animal studies met inclusion criteria human study met inclusion criteria association consumption probiotics sign calculated using producing pooled odd ratios 95 confidence interval 95 ci random effect model metaanalysis revealed significant effect probiotics incidence eae weight gain clinical symptoms however effects probiotics duration disease varied probiotic strain administration probiotics associated significant reduction risk mortality female animals moreover metaanalysis revealed promising effects probiotics prevention management eaepmid34310737 doi101111 lam13543,0.0
longterm effectiveness natalizumab patients relapsingremitting multiple sclerosis treated routine care greece results multicenter observational 5year prospective study #39 topics greece#39 clin drug investig 2021 aug 24 doi 101007 s4026102101073y online ahead printabstractbackground objectives chronic diseases like multiple sclerosis ms realworld evidence longterm treatment outcomes essential study aimed provide longterm data safety effectiveness natalizumab patients relapsingremitting ms rrms treated routine care setting greecemethods topics greece multicenter singlecountry prospective 5year observational studyresults 19apr2012 18dec2014 304 eligible adults females 632 median age natalizumab initiation 380 years median disease duration 62 years median expanded disability status scale edss score baseline 35 enrolled study 20 hospitalbased neurologists 1year annualized relapse rate arr treatment initiation 1859 arr first year treatment 0131 representing significant 93 reduction p 0001 arr median treatment period 594 months 0109 patients 1 relapse prenatalizumab year 461 received 1 prior diseasemodifying therapy 579 displayed significantly lower onnatalizumab arr 1 2 3 4 5year cumulative probabilities edss progression 32 62 97 134 174 respectively respective probabilities edss disability improvement 183 251 274 280 301 median safety data collection period 487 months 46 patients experienced 1 serious adverse event infections reported 10 commonconclusion realworld settings greece natalizumab displayed beneficial longterm effects disease activity disability progression consistent previous studies new serious safety signals emergingpmid34427893 doi101007 s4026102101073y,0.0
unveiling relationship autonomic involvement fatigue cognitive dysfunction early relapsingremitting multiple sclerosis neurol sci 2021 aug 2 doi 101007 s10072021054876 online ahead printabstractbackground fatigue common yet disabling symptom patients multiple sclerosis pwms fatigue shown associated selfreported autonomic nervous system ans symptoms particularly cognitive fatigue however question whether ans involvement related cognitive impairment never addressed performed study unveil complex relationship fatigue ans symptoms cognitive impairmentmethods prospectively recruited early pwms tested brief international cognitive assessment multiple sclerosis bicams statetrait anxiety inventory stai beck depression inventory bdi modified fatigue impact scale mfis composite autonomic symptoms scale31 compass31 scale performed comparison fatigued nonfatigued patients cognitive unimpaired impaired patients evaluated association compass31 mfis bdi stai bicams scores analysis repeated scales subscores multivariable analysis performed elucidate predictors fatigueresults fortyfour patients recruited fatigued patients higher compass31 total orthostatic intolerance secretomotor pupillomotor scores differences fatigue ans symptoms found cognitive impaired unimpaired patients mfis total score correlated stai state p 0002 trait p 0001 bdi p 0001 compass31 total p 0001 orthostatic intolerance p 0001 pupillomotor scores p 0006 multivariable analysis showed bdi p 0001 compass31 p 0021 predicted mfis score subscores analysis showed orthostatic intolerance relevant role fatigueconclusion ans symptoms closely related fatigue orthostatic intolerance may predominant role cognitive impairment seems associated ans symptomspmid34338931 doi101007 s10072021054876,0.0
structural disconnectivity paramagnetic rim lesions related disability multiple sclerosis brain behav 2021 sep 8e2353 doi 101002 brb32353 online ahead printabstractbackground people multiple sclerosis pwms lesions hyperintense rim rim+ quantitative susceptibility mapping qsm shown greater myelin damage compared rim lesions association disability yet investigated furthermore qsm rim+ rim lesions differentially impact disability disruptions structural connectivity explored test hypothesis structural disconnectivity due rim+ lesions predictive disability compared structural disconnectivity due rim lesionsmethods ninetysix pwms included study individuals expanded disability status scale edss 2 considered lower disability n 59 gray matter region change connectivity chaco score percent connecting streamlines also passing rim rim+ lesion computed adaptive boosting used classify pwms lower versus greater disability groups based chaco scores rim+ rim lesions classification performance assessed using area roc curve auc results model based chaco rim+ lesions outperformed model based chaco rim lesions auc 067 vs 063 pvalue 05 left thalamus left cerebellum important regions classifying pwms disability categoriesconclusion rim+ lesions may influential disability disruptions structural connectome rim lesions study provides deeper understanding rim+ lesion location size resulting disruption structural connectome can contribute msrelated disabilitypmid34498432 doi101002 brb32353,1.0
screening dysphagia relapsingremitting multiple sclerosis patients montenegro neurosciences riyadh 2021 oct 26 4 331338 doi 1017712 nsj2021420210063abstractobjectives perform screening dysphagia montenegrin multiple sclerosis ms patients dysphagia often neglected problem patients msmethods included 104 patients relapsingremitting ms completed 3 questionnaires dysphagia multiple sclerosis dymus eating assessment tool10 eat10 swallowing disturbance questionnaire sdq study performed clinic neurology clinical center montenegro podgorica montenegro polyclinic neuron bijelo polje montenegro november 2020 december 2020results selfreported prevalence symptom group simmilar previously reported results find correlation dymus expanded disability status scale edss reported time spent disease onset diagnosis strongly correlated reported sdq results population dysphagiapatients statistically significantly older compared nondysphagia patients statistically higher mean values population subjects proven 3 questionnaires usedconclusion importance issue just warns potientially malnutrion ms patients also important factor therapy choosing algorithm era orally used immunomodulatory drugspmid34663705 doi1017712 nsj2021420210063,0.0
kynurenine pathway chronic diseases compensatory mechanism driving force trends mol med 2021 aug 6s14714914 21 001878 doi 101016 jmolmed202107006 online ahead printabstractthe kynurenine kyn pathway kp tryptophan trp metabolism dysregulated inflammationdriven pathologies including oncological brain diseases eg multiple sclerosis ms depression thus promising therapeutic target pathological compensatory mechanisms underlie diseaseassociated kp activation growing evidence bioenergetic roles certain kp metabolites kynurenic acid ka quinolinic acid qa nad+ precursor may explain frequently observed pathological overactivation disease tissuespecific aspects negative feedback inflammatory signals balance downstream metabolites likely decisive factors interpretation imbalanced kp therapeutic strategies consider compensatory actions bioenergetic roles kp metabolites successfully design future theragnostic approaches aimed attenuating disease progressionpmid34373202 doi101016 jmolmed202107006,0.0
use commercial video games improve postural balance patients multiple sclerosisa systematic review metaanalysis randomised controlled clinical trials neurologia engl ed 2021 oct 36 8 618624 doi 101016 jnrleng201712002 epub 2019 sep 30abstractintroduction commercial video games considered effective tool improve postural balance different populations however effectiveness video games patients multiple sclerosis ms unclearobjectives analyse existing evidence effects commercial video games postural balance patients msmaterial method conducted systematic literature search 11 databases academicsearch complete amed central cinahl wos ibecs lilacs pubmed medline scielo sportdiscus science direct using following terms multiple sclerosis videogames video games exergam postural balance posturography postural control balance risk bias analysed 2 independent reviewers conducted 3 fixed effect metaanalyses calculated difference means dm 95 confidence interval 95 ci four step square test timed 25foot walk berg balance scale bbs results five randomised controlled trials included qualitative systematic review 4 metaanalysis found significant differences video game therapy group control group four step square test dm 74 95 ci 279 132 p48 i20 timed 25foot walk scores dm 15 95 ci 106 76 p75 i20 observe intergroup differences bbs scores favour video game therapy dm 530 95 ci 339721 p001 i20 greater minimum detectable change reported literatureconclusions effectiveness commercial video game therapy improving postural balance patients ms limitedpmid34654537 doi101016 jnrleng201712002,0.0
effect csf1r inhibitor glial cells population remyelination cuprizone model neuropeptides 2021 jul 13 89102179 doi 101016 jnpep2021102179 online ahead printabstractmultiple sclerosis kind autoimmune demyelinating disease pathological symptoms inflammation myelin loss astrocytosis microgliosis colony stimulating factor 1 receptor csf1r essential factor microglial function plx3397 plx specific inhibitor wstudy assessed effect different doses plx microglial ablation glial cell population remyelination process sixty male c57bl 6 mice 8 weeks old divided 6 groups animals fed 02 cuprizone diet 12 weeks microglial ablation plx 290 mg kg added animal food 3 7 14 21 days glial cell population measured using immunohistochemistry rate remyelination evaluated using electron microscopy luxol fast blue staining expression levels genes assessed qrtpcr method data analysed using graphpad prism spss software results showed administration different doses plx significantly reduced microglial cells p 001 plx administration also significantly increased oligodendrocytes population p 001 remyelination compared cuprizone mice aligned results lfb tem gene results showed plx treatment reduced csf1r expression according results administration plx 21 days enhanced remyelination increasing oligodendrocytes chronic demyelination model positive effects related reduction microgliapmid34274854 doi101016 jnpep2021102179,1.0
updated international tuberous sclerosis complex diagnostic criteria surveillance management recommendations pediatr neurol 2021 jul 24 1235066 doi 101016 jpediatrneurol202107011 online ahead printabstractbackground tuberous sclerosis complex tsc autosomal dominant genetic disease affecting multiple body systems wide variability presentation 2013 pediatric neurology published articles outlining updated diagnostic criteria recommendations surveillance management disease manifestations advances knowledge approvals new therapies necessitated revision criteria recommendationsmethods chairs working group cochairs 2012 international tsc consensus group invited meet facetoface two days 2018 world tsc conference july 25 26 dallas tx usa meeting working group cochairs worked group members via email telephone 1 review tsc literature since 2013 publication 2 confirm amend prior recommendations 3 provide new recommendations requiredresults two changes made clinical diagnostic criteria reported 2013 multiple cortical tubers radial migration lines replaced general term cortical dysplasias sclerotic bone lesions reinstated minor criterion genetic diagnostic criteria reaffirmed including highlighting recent findings individuals tsc genetically mosaic variants tsc1 tsc2 changes surveillance management criteria largely reflected increased emphasis early screening electroencephalographic abnormalities enhanced surveillance management tscassociated neuropsychiatric disorders new medication approvalsconclusions updated tsc diagnostic criteria surveillance management recommendations presented provide improved framework optimal care living tsc familiespmid34399110 doi101016 jpediatrneurol202107011,0.0
vaccination multiple sclerosis era covid19 pandemic j neurol neurosurg psychiatry 2021 aug 5jnnp2021326839 doi 101136 jnnp2021326839 online ahead printno abstractpmid34353858 doi101136 jnnp2021326839,0.0
cognitive frailty predicting death disability chinese elderly neurol res 2021 jul 2719 doi 101080 0161641220211939235 online ahead printabstractobjective although multiple sclerosis ms known immunemediated disease little known etiopathogenesis micrornas mirnas small noncoding proteins involved regulation gene expression tcell activation potential neurodegenerative diseases research topic interest recent years cytokines play important role course pathogenesis ms aim present study analyze expression levels mir20 mir21 mir26 mir155 let7 target cytokines interleukin il17 il23 order evaluate relationship ms mirnas modulate expression cytokines involved autoimmune pathwaymethodsthe study included 20 relapsingremitting multiple sclerosis ms patients least 18 years age undergoing outpatient immunomodulatory therapy 20 healthy unrelated individuals systemic disease taking medication control group peripheral blood samples collected participants edtacontaining tubes plasma isolated cdna synthesis cdna samples mirna expression levels quantitatively analyzed via melting curve analysis using miscript sybr green kit realtime pcr deviceresults comparison mirna expression levels peripheral blood samples ms patients healthy subjects revealed ms patients significant upregulation mir20 downregulation mir26 mir155 compared control group p0005 conclusionsdysregulation mirna expression may play role pathogenesis mspmid34313186 doi101080 0161641220211939235,0.0
gut microbiota forty cases egyptian relapsing remitting multiple sclerosis iran j microbiol 2021 oct 13 5 632641 doi 1018502 ijmv13i57428abstractbackground objectives gut microbiota assumed play essential role pathogenesis multiple sclerosis ms study aimed investigate abundance gut microbiota among egyptian patients relapsing remitting multiple sclerosis rrms materials methods forty cases rrms diagnosed according mcdonald diagnostic criteria 2017 recruited consecutively department neurology assiut university hospitals results compared 22 healthy age sex matched control subjects dna extracted stool measures made concentration copy number bacterial organisms realtime pcr using group specific primers 16s rrna targeting predominant genera gut microbiota previously hypothesized participate ms pathogenesisresults mean age 314 88 yrs 75 patients women mean sd edss score 343 135 seven cases cervical cord plaques 17 significantly increased copy numbers desulfovibrio actinobacteria firmcutes lactic acid bacteria patients compared control group contrast significantly lower level clostridium cluster iv patients patients edss 35 significantly higher copy number actinobacteria bacteroidetes bifidobacterium compared patients edss 35 significant negative correlation duration illness copy number firmcutes akkermansia lactic acid bacteria p 001 004 0004 respectively conclusion changes gut microbiota associated exacerbation ms disease disruption intestinal microbiota results depletion enrichment certain bacteria may affect immune balance leading predisposition mspmid34900161 pmcpmc8629825 doi1018502 ijmv13i57428,0.0
neurophysiological assessment brachioradial pruritus patients arq neuropsiquiatr 2021 oct 79 10 900903 doi 101590 0004282xanp20200333abstractbackground pruritus common complaint dermatology wartenberg 1943 associated pruritus neuropathy relating posterior antebrachial cutaneous nerve neuropathy 1968 waisman described patients frequent pruritus complaints upper limb summer named brachioradial summer pruritus currently pruritus named brachioradial pruritus brp brp characterized chronic pruritus usually localized long duration without apparent cutaneous abnormalities neurological disorders central peripheral nervous systems including multiple sclerosis associated pruritusobjective investigate correlations symptomatic dermatomes alterations myotomes evidenced electroneuromyography enmg methods fortysix patients brp dermatological diagnoses subjected upper limb enmgresults among 46 patients c5 c8 dermatomal pruritus evaluated 113 symptomatic dermatomal areas overall 39 85 patients radicular involvement 28 60 agreement complaint enmg findings p0015 total 80 patients complaints c7 47 c6 radicular involvement levelconclusions among patients presented complaints 47 80 respectively enmg alterations c6 c7 myotomes conclude peripheral nervous system involvement associated brppmid34706020 doi101590 0004282xanp20200333,0.0
recent insights astrocyte mechanisms cns homeostasis pathology repair j neurosci res 2021 jul 14 doi 101002 jnr24922 online ahead printabstractastrocytes play essential roles development homeostasis injury repair central nervous system cns development tightly regulated distinct spatial temporal cues embryogenesis adulthood throughout cns astrocytes several important responsibilities regulating blood flow permeability bloodcns barrier glucose metabolism storage synapse formation function axon myelination cns pathologies astrocytes also play critical parts injury repair mechanisms upon injury undergo robust phenotypic shift known reactive astrogliosis results constructive deleterious outcomes astrocyte activation migration site injury provides early defense mechanism minimize extent injury enveloping lesion area however astrogliosis also contributes inhibitory microenvironment cns injury potentiate secondary injury mechanisms inflammation oxidative stress glutamate excitotoxicity facilitate neurodegeneration cns pathologies intriguingly reactive astrocytes increasingly focus current therapeutic strategies activation can modulated toward neuroprotective reparative phenotype review will discuss recent advancements knowledge regarding development role astrocytes healthy pathological cns will also review astrocytes genetically modified optimize reparative potential injury may transdifferentiated neurons oligodendrocytes promote repair cns injury neurodegenerationpmid34259342 doi101002 jnr24922,1.0
transcranial direct current stimulation management neuropathic pain narrative review pain physician 2021 sep 24 6 e771e781abstractbackground neuropathic pain np common often resistant conventional analgesics among different types noninvasive brain stimulation techniques transcranial direct current stimulation tdcs widely used mitigate pain patients npobjective aim study review effects tdcs management various types npstudy design narrative reviewmethods pubmed search conducted articles published october 1 2020 using tdcs treat np key search phrase transcranial direct current stimulation pain used identify potentially relevant articles following inclusion criteria applied article selection 1 studies involving patients np 2 studies used tdcs treat np review articles excluded analysisresults total 524 potentially relevant articles identified reading titles abstracts assessing eligibility based fulltext articles 34 publications included review overall results suggest tdcs induced pain reduction patients np due stroke spinal cord injury multiple sclerosis trigeminal neuralgia insufficient evidence validate efficacy tdcs treating painful conditions complex regional pain syndrome phantom pain np various originslimitations review include studies indexed databases pubmedconclusion results included studies suggest tdcs may beneficial treating patients np due stroke spinal cord injury multiple sclerosis trigeminal neuralgia studies recommended validate efficacy tdcs treating types npspmid34554695,0.0
impact immunoablation autologous hematopoietic stem cell transplantation ahsct treatment cost multiple sclerosis realworld nationwide study value health reg issues 2021 apr 14 25104107 doi 101016 jvhri202010008 online ahead printabstractobjectives provide realworld data impact autologous hematopoietic stem cell transplantation ahsct treatment costs patients multiple sclerosis ms polandmethods medical data 105 patients underwent ahsct years 2011 2016 obtained national health fund nhf database treatment costs calculated public payers perspective per patientyear total available period well 12 months ahsct statistical analysis performed using matlab 2016bresults mean treatmentrelated costs covered nhf per patientyear transplantation 43149 11888 respectively average cost diseasemodifying drugs per patient reduced 24979 year 653 year ahsctconclusions although initial cost ahsct high costs involving ahsct postahsct treatment according analysis pay 39 years compared costs diseasemodifying drug therapy aggressive ms study provides evidence ahsct can lead significant savings treatment costs aggressive ms public payers perspectivepmid33865219 doi101016 jvhri202010008,0.0
state science cannabis cannabinoids palliative medicinethe potential bmj support palliat care 2021 apr 26bmjspcare2021002888 doi 101136 bmjspcare2021002888 online ahead printabstractcannabinoids chemicals derived naturally cannabis plant synthetically manufactured interact directly cannabinoid receptors share chemical similarity endocannabinoids within palliative medicine cannabinoid receptors cb1 cb2 may modulate cancer symptoms appetite chemotherapyinduced nausea vomiting mood pain sleep disorders opioid cannabinoid receptors overlapping neuroanatomical receptor distribution particularly dorsal horn dorsal striatum locus coeruleus favourable safety profile compared opioids cannabisbased medicines help chronic pain cannabidiol cbd antiinflammatory properties tetrahydrocannabinol thc psychoactive substance issues mood sleep nabiximols sativex cbdthc combination food drug administration approved multiple sclerosis symptoms epilepsy swift societal evolution attitudes use cannabis cannabinoid medicines chronic pain usa 33 states now legalised prescriptionbased medical cannabis several medical conditions canada legislation since 2001 authorising medical use european union eu recently declared eu citizens must access medical cannabis next 4 years integration medicine routine clinical use cannabis fraught information gaps regulatory issues scarcity research patient comprehensive assessment riskbenefit discussion cannabisbased intervention avoid possible complications hallucinations psychosis potential cardiac harmpmid33903260 doi101136 bmjspcare2021002888,0.0
sarscov2 antibody dynamics bcell memory response overtime covid19 convalescent subjects clin microbiol infect 2021 may 8s1198743x 21 002299 doi 101016 jcmi202105008 online ahead printabstractobjectives worldwide spread covid19 disease highlights need assessment longterm humoral immunity convalescent subjects objectives evaluate longterm igg sarscov2 antibody response bcell memory response covid19 convalescent subjectsmethods blood samples collected cohort subjects recovering covid19 disease healthy subjects donated blood sarscov2 igg antibodies quantitatively detected elisa using antis1 spike igg sarscov2 spikespecific igg memory bcells evaluated randomly selected group covid19 recovering subjects reversed bcell flurospot based human igg sarscov2 receptorbinding domain statistical analysis performed clinical variables time postcovid19 infectionresults antibody response detected 26 392 66 covid19 convalescent subjects period 9 months level antibodies decreased 50 stabilized 6 months prevailed protective level 9 months differences found regarding igg sarscov2 antibody levels age gender major blood types overtime covid19 asymptomatic subjects differ antibody level overtime subjects mild severe disease repeated paired igg sarscov2 antibody level analyses disclosed 6 9 months 153 9 59 158 3 19 subjects became sarscov2 igg seronegative respectively low antibody level 3 months rate antibody decline affected age gender clinical symptomatology subgroup recovering subjects memory bcell response 9months post covid19 infection undetectable 318 14 44 subjects correlation age sarscov2 antibody level time postinfectionconclusions majority covid19 convalescent subjects develop igg sarscov2 antibody response prevails protective level period 9months regardless age gender major blood types clinical symptomatologypmid33975009 doi101016 jcmi202105008,0.0
simultaneous t 2 t2 mapping multiple sclerosis lesions radial rareepi magn reson med 2021 may 5 doi 101002 mrm28811 online ahead printabstractpurpose characteristic mri features multiple sclerosis ms lesions make conceptually appealing pursue parametric mapping techniques support simultaneous generation quantitative maps 2 mr contrast mechanisms present modular rapid acquisition relaxation enhancement rare epi hybrid facilitates simultaneous t2 t 2 mapping 2in1rareepi methods 2in1rareepi first echoes echo train acquired rare module later echoes acquired epi module define fraction echoes covered rare epi module error analysis t2 t 2 conducted monte carlo simulations radial kspace sampling implemented acceleration r 2 feasibility 2in1rareepi simultaneous t2 t 2 mapping examined phantom study mimicking t2 t 2 relaxation times brain validation 2in1rareepi benchmarked versus multi spinecho mse multi gradientecho mgre techniques clinical applicability 2in1rareepi demonstrated healthy subjects ms patientsresults good agreement t2 t 2 values derived 2in1rareepi t2 t 2 reference values obtained mse mgre phantoms healthy subjects patients ms lesions t2 t 2 maps deduced 2in1rareepi just clearly delineated reference maps calculated mse mgreconclusion work demonstrates feasibility radially sampled 2in1rareepi simultaneous t2 t 2 mapping ms patientspmid33951214 doi101002 mrm28811,0.0
pedsql multiple sclerosis module domain item development qualitative methods j child neurol 2021 may 288830738211015016 doi 101177 08830738211015016 online ahead printabstractbackground objective qualitative methods study develop domains items support content validity pediatric quality life inventory pedsql multiple sclerosis module youth pediatriconset multiple sclerosismethods literature review multiple sclerosisspecific questionnaires clinical research conducted generate domains expert panel composed 12 neurologists pediatriconset multiple sclerosis specialists provided feedback conceptual framework focus interviews 9 youth pediatriconset multiple sclerosis 6 parents conducted develop relevant domains item content patient parent perspective cognitive interviews phase 9 youth pediatriconset multiple sclerosis 6 parents provided feedback item content relevance importance understandability pediatriconset multiple sclerosisspecific domains items final interview phase 5 youth pediatriconset multiple sclerosis 5 parents comprised pilot testing new pedsql ms moduleresults eighteen domains derived qualitative methods item content saturation achieved 100 items based 40 interviews 23 youth pediatriconset multiple sclerosis aged 1021 years 17 parents domains derived include general fatigue sleep rest fatigue cognitive functioning tingling sensations numbness sensations physical weakness pain speech balance fine motor vision urination constipation bowel incontinence worry communication treatment medicinesconclusions qualitative methods involving 23 youth pediatriconset multiple sclerosis 17 parents domain item development process support content validity new pedsql ms module future plans include national field test pedsql ms module scales itemspmid34048290 doi101177 08830738211015016,0.0
dimethyl fumarate abridged tauo amyloidopathy dgalactose ovariectomyinduced alzheimer#39 slike disease modulation ampk sirt1 akt creb bdnf akt gsk3 adiponectin adipo1r nfb il1 ros trajectories neurochem int 2021 may 27105082 doi 101016 jneuint2021105082 online ahead printabstractsince role estrogen postmenauposalassociated dementia still debatable issue urges search medications dimethyl fumarate dmf drug used treatment multiple sclerosis shown neuroprotective effect neurodegenerative diseases accordingly present study aimed evaluate effect dmf experimental model alzheimer disease ad using dgalactose dgal administered ovariectomized ovx rats resembling postmenopausal dementia paradigm adult 18month old female wistar rats allocated shamoperated ovx dgal groups either left untreated treated dmf 56 days starting three weeks shamoperation ovariectomy dmf succeeded ameliorate cognitive learning short longterm memory deficits enhance dampened overall activity barnes ymaze tests behavioral upturns associated increased intact neurons nissl stain reduction ovx dgalmediated hippocampal ca1 neurodegeneration astrocyte activation assessed gfap immunoreactivity mechanistically dmf suppressed hippocampal contents adsurrogate markers viz apolipoprotein apo e1 bace1 a42 hyperphosphorylated tau additionally dmf augmented neuroprotective parameters pakt downstream target creb bdnf besides activated ampk enhanced sirt1 well antioxidant defenses sod gsh hand dmf inhibited transcription factor nfb il1 adiponectin adiponectin receptor type adipor 1 gsk3 mda accordingly postmenopausal ad model dmf treatment pursuing adiponectin adipor1 ampk sirt1 akt creb bdnf akt gsk3 apoe1 quartet hampered associated tauo amyloidopathy nfbmediated oxidative inflammatory responses advance insights antiamnesic effectpmid34052296 doi101016 jneuint2021105082,1.0
characteristics optimal treatment urolithiasis associated tuberous sclerosis complex int urol nephrol 2021 apr 25 doi 101007 s11255021028711 online ahead printabstractpurpose common renal symptoms tuberous sclerosis complex tsc angiomyolipomas amls renal cysts however patients tsc also develop urolithiasis retrospectively investigated characteristics treatment urolithiasis associated tscmethods analyzed 142 patients met diagnostic criteria tsc 20 141 urolithiasis compared patients characteristics urinary specific gravity urine ph serum calcium intact parathyroid hormone urolithiasis nonurolithiasis groups urolithiasis group stone characteristics various treatments analyzedresults antiepileptic drugs topiramate zonisamide frequently administered urolithiasis group nonurolithiasis group p 0013 p 0048 respectively urine specific gravity urine ph levels higher urolithiasis group nonurolithiasis group p 0005 p 0042 respectively multivariate logistic regression analysis demonstrated urinespecific gravity p 0018 odds ratio 1471 95 confidence interval 10981872 significant predictor tscassociated urolithiasis four patients receive extracorporeal shock wave lithotripsy due risk bleeding amlconclusion patients tsc increased urine specific gravity alkaline urine longer administration topiramate zonisamide tend demonstrate increased risk developing urolithiasis therefore cases require adequate care urolithiasis comorbid tscassociated aml treatment options limited cases multiple amls around stone due increased risk hemorrhagepmid33899133 doi101007 s11255021028711,0.0
invivo 1hmrs shortecho time technique 7t quantification metabolites chronic multiple sclerosis neuromyelitis optica brain lesions normal appearing brain tissue neuroimage 2021 may 29118225 doi 101016 jneuroimage2021118225 online ahead printabstractmagnetic resonance spectroscopy mrs allows noninvasive quantification neurochemicals potential differentiate pathologically distinct diseases multiple sclerosis ms aqp4abpositive neuromyelitis optica spectrum disorder aqp4abnmosd study characterised metabolite profiles brain lesions 11 ms 4 aqp4abnmosd patients using optimised mrs methodology ultrahigh field strength 7t incorporating correction t2 water relaxation differences lesioned normal tissue ms metabolite results keeping existing literature total nacetylaspartate naa lower lesions compared normal appearing brain white matter nawm reciprocal findings myoinositol unexpected subtlety revealed technique total naa differences likely driven naaglutamate naag ubiquitous cns molecule functions quite distinct naa though commonly quantified together naa mrs studies total naa surprisingly aqp4abnmosd showed significant differences total naa naa naag myoinositol lesion nawm sites differences ms aqp4abnmosd priori hypotheses posthoc testing revealed significant correlation nawm insnaa disability measured edss disease groups combined driven ap4abnmosd group utilising optimised mrs methodology study highlights underexplored subtleties mrs profiles absence myoinositol concentration differences aqp4abnmosd brain lesions versus nawm potential influence naag differences lesions normal appearing white matter mspmid34062267 doi101016 jneuroimage2021118225,0.0
botulinum toxin injections japanese patients urinary incontinence caused neurogenic detrusor overactivity clinical evaluation onabotulinumtoxina randomized placebocontrolled doubleblind trial openlabel extension int j urol 2021 jun 1 doi 101111 iju14602 online ahead printabstractobjective assess efficacy safety botulinum toxin treatment onabotulinumtoxina 200 units japanese patients neurogenic detrusor overactivity caused spinal cord injury multiple sclerosismethods patients urinary incontinence refractory pharmacological treatment enrolled randomized phase iii trial single dose onabotulinumtoxina n 11 placebo n 10 given doubleblind phase repeat injections onabotulinumtoxina given subsequent openlabel phase outcomes included urinary incontinence episodes urodynamics patientreported outcomes adverse eventsresults onabotulinumtoxina group showed numerically greater reduction number urinary incontinence episodes per day placebo group difference groups week 6 302 95 confidence interval 585 019 onabotulinumtoxina group also showed greater improvements urodynamic assessments adverse events related onabotulinumtoxina injections hematuria urinary retention urinary bladder hemorrhage autonomic dysreflexia epididymitis events deemed mild moderateconclusions intradetrusor injections onabotulinumtoxina efficacious tolerable japanese patients neurogenic detrusor overactivityrelated symptoms difficult manage anticholinergics 3 adrenergic receptor agonistspmid34075630 doi101111 iju14602,0.0
clinical decision making mog antibodyassociated disease lancet neurol 2021 sep 20 9 695697 doi 101016 s14744422 21 002477no abstractpmid34418387 doi101016 s14744422 21 002477,0.0
rituximab ocrelizumabinduced early lateonset neutropenia multiple sclerosis patient neurol sci 2021 jun 1 doi 101007 s10072021053571 online ahead printno abstractpmid34075515 doi101007 s10072021053571,0.0
two healthy lifestyle scores associated lower subsequent fatigue risk using inverse probability weighting international longitudinal cohort people multiple sclerosis eur j neurol 2021 jun 3 doi 101111 ene14956 online ahead printabstractbackground several modifiable lifestyle factors associated onset health outcomes multiple sclerosis ms including clinically significant fatigue combined lifestyle score approach represents one method assessing relationship clinical outcomesobjectives examine association two lifestyle scores clinically significant fatigue change thereof 25 years followup using inverse probability treatment weighting iptw methods used data sociodemographic lifestyle clinical characteristics surveyed international cohort people ms baseline 25year followup fatigue defined fatigue severity scale fss5 healthy lifestyle healthy lifestyle index score hlis smoking nutrition alcohol physical activity snap score analyses iptw accounting age sex ms type disability treated comorbidity number immunomodulatory medication use prescription antifatigue medication use ongoing relapse symptomsresults 1 268 participants completed fss timepoints approximately 62 fatigue using doubly robust iptw high 11 20 hlis or090 95 ci 081098 high 3 5 snap or082 95 ci 073090 associated lower risk fatigue followup evaluating change fatigue higher snap score associated lower risk fatigue or089 95 ci 080097 hlis reach statistical significance or093 95 ci 085101 conclusion results suggest robust role key lifestyle factors preventing clinically significant fatigue may represent place lifestyle modification improving clinical outcomes mspmid34081818 doi101111 ene14956,0.0
diffusion tensor imaging reveals greater microstructure damage lesional tissue shrinks cerebrospinal fluid multiple sclerosis j neuroimaging 2021 jun 3 doi 101111 jon12891 online ahead printabstractbackground purpose atrophied t2 lesion volume lv reflecting complete transformation lesions cerebrospinal fluid csf associated disease progression multiple sclerosis ms underlying damage leading lesion destruction remains poorly understood objective study use diffusion tensor imaging dti investigate extent microstructural tissue damage baseline lesions subsequently transform csfmethods ninetynine ms patients 67 relapsingremitting ms rrms 32 progressive pms pms imaged baseline average 53 06 years followup assessments included t2 lv dti baseline atrophied t2 lv followup lesioned areas became atrophied t2 lv compared baseline lesional dti metrics compared rrms versus pms patients patients disability progression dp n 35 versus nondp n 64 using ancova modelsresults lesion tissue developed atrophied t2 lv significantly different baseline dti parameters compared nonatrophied t2lv tissue p0001 largest effect freewater d 2739 baseline tissue characteristics future atrophied t2 lv significantly different groups however dp patients developed greater atrophied t2 lv 377 vs 83 mm3 p 0001 conclusions extensive microstructural damage characterizes lesions replaced csf independently disease phenotype future dp greater atrophied t2 lv predicts dppmid34081373 doi101111 jon12891,0.0
neurologic features associated sarscov2 infection children case series report j child neurol 2021 mar 1883073821989164 doi 101177 0883073821989164 online ahead printabstractintroduction although multiple neurologic manifestations associated sarscov2 infection described adults little information presented children described neurologic manifestations associated covid19 pediatric populationmethods retrospective case series report included patients younger 18 years admitted confirmed sarscov2 infection neurologic manifestations hospital santiago chile demographics clinical presentations laboratory results radiologic neurophysiological studies treatment outcome features described cases described based whether presented predominantly central peripheral neurologic involvementresults thirteen 90 144 patients admitted confirmed infection presented newonset neurologic symptoms 4 patients showed epilepsy exacerbation neurologic manifestations ranged mild headache muscle weakness anosmia ageusia severe status epilepticus guillainbarr syndrome encephalopathy demyelinating events conclusions found wide range neurologic manifestations children confirmed sarscov2 infection general neurologic symptoms resolved systemic presentation subsided essential recognize report main neurologic manifestations related new infectious disease pediatric population evidence needed establish specific causality nervous system involvementpmid33646895 doi101177 0883073821989164,1.0
nonlesional diffusely abnormal appearing white matter clinically isolated syndrome prevalence association clinical mri features risk conversion multiple sclerosis j neuroimaging 2021 jun 15 doi 101111 jon12900 online ahead printabstractbackground purpose diffusely abnormal white matter dawm nonlesional mri abnormality identified 25 patients multiple sclerosis ms yet investigated patients earlier disease stage namely clinically isolated syndrome cis goals study 1 determine prevalence dawm patients cis suggestive ms 2 evaluate association dawm demographic clinical mri features 3 evaluate prognostic significance dawm conversion cis msmethods one hundred fortytwo cis participants categorized dawm nondawm groups baseline followed 24 months ms diagnosis primary outcome conversion ms 2005 mcdonald criteria within 6 monthsresults dawm present 275 participants positively associated brainstem symptom onset receiving corticosteroids dissemination space t2 lesion volume dawm associated increased risk conversion ms 6 months adjustment age disability hazard ratio hr 224 p 0004 association remained trendlevel adjustment highrisk imaging features hr 168 p 010 conclusions dawm present similar proportion patients cis clinically definite ms associated increased risk conversion ms 6 monthspmid34128576 doi101111 jon12900,0.0
preliminary evidence blunted humoral response sarscov2 mrna vaccine multiple sclerosis patients treated ocrelizumab neurol sci 2021 jun 15 doi 101007 s10072021053977 online ahead printabstractobjectives several concerns regard immunogenicity sarscov2 vaccines people multiple sclerosis pwms since majority treated immunomodulating immunosuppressive disease modifying therapies report first data humoral response mrna sarscov2 vaccine case series 4 pwms treated ocrelizumab ocr compared group healthy subjects hs methods collected serum samples 0 14 21 days first dose 7 days second dose bnt162b2mrnacovid19 vaccine 55 healthcare workers 4 relapsing pwms ocr history covid19 infection sera tested using liaisonsarscov2 trimericsigg assay diasorinspa detection igg antibodies sarscov2 spike protein antispike iggtiters expressed binding antibody units bau international standard unitresults baseline subjects negative antispike igg seven days second dose vaccine hs mounted significant humoral response geometric mean 20104 bau ml ci 95 151272672 4 pwms showed lower response range 481175 bau ml discussion humoral response bnt162b2mrnavaccine pwms treated ocr clearly blunted data urgently needed confirm expand preliminary results develop strategies optimize response sarscov2 vaccines pwms ocrpmid34128150 doi101007 s10072021053977,0.0
contribution sleep disturbances fatigue ms prospective study using clinical polysomnographic parameters eur j neurol 2021 jun 18 doi 101111 ene14984 online ahead printabstractbackground fatigue among frequent disabling symptoms multiple sclerosis ms close relation fatigue sleep quality hypothesized study investigated contribution sleep disturbances measured clinical polysomnographic psg parameters fatigue msmethods prospective instrumental study performed neurocenter southern switzerland demographic data clinical characteristics including fatigue measured modified fatigue impact scale mfis neurological disability psychiatric symptoms medications sleep related variables collected baseline visit home fullnight psg associations sleep related variables mfis tested using partial correlations adjusted demographic sleepunrelated clinical factorsresults seventysix patients included study 53 697 mfis 38 points median495 iqr310620 mfis scores positively associated age neurological disability symptoms depression anxiety use benzodiazepines selective serotonin reuptake inhibitors adjusting variables presence restless leg syndrome rls r037 p0005 periodic leg movements index r033 p0014 associated mfis excessive daytime sleepiness total sleep time sleep efficiency respiratory disturbances percentage time spent different sleep stages n1 n2 n3 rem associated fatigueconclusions ms patients diagnosis rls significantly higher global fatigue scores compared without rls future studies investigate whether medical treatment rls can ameliorate fatiguepmid34143510 doi101111 ene14984,0.0
glucosamine promotes seizure activity via activation pi3k akt pathway epileptic rats epilepsy res 2021 jun 3 175106679 doi 101016 jeplepsyres2021106679 online ahead printabstractcontext glucosamine amino monosaccharide small molecular weight protective effect various neurological diseases including multiple sclerosis encephalomyelitis interestingly lowdose glucosamine exhibited antiepilepsy activity recent studies shown activation protein kinase b akt signaling pathway may promote epilepsy glucosamine can increase level akt phosphorylation brain tissue may aggravate epilepsy hence speculate higher dose glucosamine may aggravate epilepsy via akt signalingobjective investigate effect glucosamine behavior electrophysiology epileptic rats pi3k akt pathwaymethods glucose 20 g kg glucosamine 0 05 10 20 g kg added 2 ml drinking water respectively acute seizure rat model lithiumpilocarpine ptzkindling constructed observe effects different doses glucosamine epileptic behavior hippocampal electrical activity meanwhile changes akt detected western blotresults epileptic seizures induced single dose pilocarpine ptz 20 g kg glucosamine significantly prolonged duration severity epileptic seizures enhanced hippocampal electrical activity energy density increased phosphorylated akt levels glucosamine dose 20 g kg also significantly increased total onset energy density furthermore 20 g kg glucosamine facilitated development chronic ptzkindling processconclusions glucosamine may exacerbate acute chronic epileptic seizures via activation pi3k akt pathway rats experimental epilepsypmid34166966 doi101016 jeplepsyres2021106679,0.0
lateonset neutropenia lon recur ms patient second cycle ocrelizumab case report neurol sci 2021 jun 25 doi 101007 s10072021053799 online ahead printno abstractpmid34170432 doi101007 s10072021053799,0.0
improved particle swarm optimized deep convolutional neural network superpixel clustering multiple sclerosis lesion segmentation brain mri imaging int j numer method biomed eng 2021 jun 28e3506 doi 101002 cnm3506 online ahead printabstracta central nervous system cns disease affecting insulating myelin sheaths around brain axons called multiple sclerosis ms todays world ms extensively diagnosed monitored using mri structural mri sensitivity dissemination white matter lesions respect space time main aim study propose multiple sclerosis lesion segmentation brain mri imaging using optimized deep convolutional neural network superpixel clustering three stages included proposed methodology preprocessing b segmentation superpixel c classification superpixel first stage image enhancement skull stripping done performing preprocessing step second stage ms lesion nonms lesion regions segmented applying slico algorithm slice volume fourth stage cnn training classification performed using segmented lesion nonlesion regions handle complex task newly developed improved particle swarm optimization ipso based optimized convolutional neural network classifier applied clinical ms data approach exhibits significant increase accuracy segmenting wm lesions compared rest evaluated methodspmid34181310 doi101002 cnm3506,1.0
reliability urinary symptom questionnaires people neurogenic bladder usqnb void use indwelling catheters spinal cord 2021 aug 4 doi 101038 s4139302100665x online ahead printabstractstudy design descriptive psychometrics studyobjectives neurogenic lower urinary tract dysfunction nlutd also called neurogenic bladder nb common disruptive condition variety neurologic diagnoses team developed patientcentered instruments urinary symptom questionnaires people neurogenic bladder usqnb specific people nlutd manage bladders intermittent catheterization ic indwelling catheters idc void v article reports evidence reliability idc v instrumentssetting online surveys completed individuals united states nlutd due spinal cord injury sci multiple sclerosis ms manage bladder idc sci n 306 voiding sci n 103 ms n 383 methods reliability estimates based endorsement items usqnbidc usqnbv reliability evidence representativeness symptoms national sample determining endorsement 10 internal consistency estimates cronbachs alpha item correlation coefficient icc interrelatedness items inferred bayesian network bn also tested whether onefactor conceptualization urinary symptoms nlutd supportable either instrumentresults items endorsed 20 samples urine quality symptoms tended commonly endorsed instruments cronbachs alpha icc estimates high 074 suggestive redundancy bns showed interpretable associations among items discover uninterpretable unexpected associations neither instrument fit onefactor model expectedconclusions usqnbidc usqnbv instruments show sufficient multidimensional reliability implementation studypmid34345005 doi101038 s4139302100665x,0.0
cladribine suppresses disease activity neuromyelitis optica spectrum disorder two year follow study eur j neurol 2021 jul 7 doi 101111 ene15012 online ahead printabstractbackground neuromyelitis optica spectrum disorder nmosd difficult treat condition cladribine selectively transiently depletes b t lymphocytes leading longlasting immune reconstitution report describes observations 24 months followup cladribine nmosd patientsmethods retrospective analysis case series including 12 seropositive patients nmosd patients given cladribine subcutaneous injections series several twoday cycles 20 mg administered intervals 46 weeks thus full treatment course delivered cumulative bioavailable dose similar approved treatment multiple sclerosis annualized relapse rate arr disability expanded disability status scale score safety 24 months preceding 24 months following initiation cladribine treatment assessedresults mean arr 24 month preceding cladribine treatment 104 95 ci 067 162 mean arr 24 month following initiation cladribine treatment 021 95 ci 008 056 ratio rate events post vs prior cladribine initiation 020 95 ci 007 059 highly significant p00073 edss score change followup period 2517 meansd compared baseline 2515 meansd serious adverse events considered linked cladribine observed followupconclusions cladribine safe nmosd patients 2year observation period cladribine treatment associated clinical stabilization evidenced significantly decreased annualized relapse rate progression edss scorespmid34233064 doi101111 ene15012,0.0
mri correlates multiple sclerosis immunopathological patterns ann neurol 2021 jul 7 doi 101002 ana26163 online ahead printabstractobjective histology reveals early active multiple sclerosis lesions can classified three main interindividually heterogeneous intraindividually stable immunopathological patterns active demyelination patterns iiii pattern ii tcell macrophageassociated demyelination suggested pattern ii showing signs humoral immune response pattern iii characterized inflammatory lesions oligodendrocyte degeneration patterns suggest pathogenic heterogeneity postulated distinct mri correlates may serve biomarkersmethods evaluated international collaborative retrospective cohort study mri lesion characteristics 789 conventional prebiopsy followup mris relation histopathologically classified immunpathological patterns n161 subjects lesion edge features n112 results strong association ringlike enhancement hypointense t2weighted rim t2w rim pattern ii pattern iii observed fraction pattern iii patients showed ringlike enhancement always atypical ringlike enhancement t2w rims colocalized ringlike enhancement showed strong association macrophage rims shown histology strong concordance mri lesion characteristics meaning different lesions showed features found comparing biopsied nonbiopsied lesions given time point indicating lesion homogeneity within individual patientsinterpretation provide robust evidence mri characteristics reflect specific morphological features ms immunopatterns ringlike enhancement t2w hypointense rims might serve valuable noninvasive biomarker differentiate pathological patterns demyelination article protected copyright rights reservedpmid34231919 doi101002 ana26163,1.0
riluzole ameliorate disease caused cytoplasmic tdp43 mouse model amyotrophic lateral sclerosis eur j neurosci 2021 aug 13 doi 101111 ejn15422 online ahead printabstractamyotrophic lateral sclerosis als neurodegenerative disease commonly treated riluzole small molecule may act via modulation glutamatergic neurotransmission however riluzole modestly extends lifespan people living als precise mechanisms action remain unclear als cases characterised accumulation cytoplasmic tar dna binding protein 43 kda tdp43 understanding effects riluzole models closely recapitulate tdp43 pathology may provide insights development improved therapeutics therefore investigated effects riluzole female transgenic mice inducibly express nuclear localisation sequence nls deficient human tdp43 neurons nefhtta tetohtdp43nls rnls mice riluzole treatment first day htdp43nls expression alter disease onset weight loss performance multiple motor behavioural tasks riluzole treatment also alter tdp43 protein levels solubility phosphorylation although identified significant decrease glua2 glua3 proteins cortex rnls mice riluzole ameliorate diseaseassociated molecular phenotype likewise riluzole alter diseaseassociated atrophy hindlimb muscle rnls mice finally riluzole treatment beginning disease onset rnls mice similarly effect progression latestage disease animal survival together demonstrate specific glutamatergic receptor alterations muscle fibretype changes reminiscent als female rnls mice riluzole effect disease phenotypes future targeting pathways related accumulation tdp43 pathology may needed develop better treatments alspmid34390052 doi101111 ejn15422,0.0
prevalence pediatric multiple sclerosis germany nationwide populationbased analysis eur j neurol 2021 jul 9 doi 101111 ene15015 online ahead printabstractbackground prevalence data needed reveal trends regarding pediatric multiple sclerosis ms situation worldwide aim identify changes ms diagnosis prevalence pediatric patients 10year period germanymethods analysis based nationwide outpatient claims data children aged 18 years covered german statutory health insurance n 201811 381 939 people ms pwms 1 documented ms diagnosis icd10gm code g35 annual pediatric ms diagnosis prevalence analyzed regarding age sex place residence 20092018results prevalence pediatric ms developed 53 2009 54 2018 100 000 insured aged 18 years ms prevalence patients aged 1517 years showed moderate increase 10 years 196227 100 000 patients 14 years showed slight decrease 1917 100 000 sex ratio femalemale 2018 relatively balanced pwms aged 14 132 femaledominated aged 1517 years 247 formerly different prevalence pediatric ms east west germany converged since 2012conclusions far largest study pediatric ms prevalence terms source population size 87 german children 18 years age n 2018 11 381 939 study period 20092018 worldwide analyses revealed increase ms prevalence femaledominated sex ratio older adolescents compared younger patientspmid34242461 doi101111 ene15015,0.0
gut microbiome associated multiple sclerosis activity children ann clin transl neurol 2021 aug 19 doi 101002 acn351441 online ahead printabstractobjective identify features gut microbiome associated multiple sclerosis activity timemethods used 16s ribosomal rna sequencing stool 55 recently diagnosed pediatriconset multiple sclerosis patients microbiome features included abundance individual microbes networks identified weighted genetic correlation network analyses prenticewilliamspeterson cox proportional hazards models estimated associations features three disease activity outcomes clinical relapses new enlarging t2 lesions new gadoliniumenhancing lesions brain mri analyses adjusted age sex diseasemodifying therapiesresults participants followed average 21 years five microbes nominally associated three disease activity outcomes multiple testing correction included butyrate producers odoribacter relapse hazard ratio 046 95 confidence interval 024 088 butyricicoccus relapse hazard ratio 049 95 confidence interval 028 088 two networks cooccurring gut microbes significantly associated higher hazard mri outcomes gadoliniumenhancing lesion hazard ratios 95 confidence intervals modules 32 33 129 108 154 142 118 171 respectively t2 lesion hazard ratios 95 confidence intervals modules 32 33 134 115 156 141 121 164 respectively metagenomic predictions networks demonstrated enrichment amino acid biosynthesis pathwaysinterpretation individual networks gut microbes associated longitudinal multiple sclerosis activity known functions metagenomic predictions microbes suggest important role butyrate amino acid biosynthesis pathways provides strong support future development personalized microbiome interventions modify multiple sclerosis disease activitypmid34409759 doi101002 acn351441,0.0
potential improved retention rate personalized antiseizure medication selection registerbased analysis epilepsia 2021 jul 9 doi 101111 epi16987 online ahead printabstractobjective first antiseizure medication asm ineffective intolerable 50 epilepsy cases selection 25 available asms guided epilepsy factors also age comorbidities randomized evidence particular patient subgroups seldom available asked whether register data used retention rate calculations based demographics comorbidities asm history quantified potential improvement retention rates first asm several large epilepsy cohorts also describe retention rates patients epilepsy traumatic brain injury dementia patient groups little available evidencemethods used medical demographic drug prescription data epilepsy cohorts comprehensive swedish registers containing 6380 observations analyzing 381 840 prescriptions studied retention rates first secondline asms patients epilepsy multiple sclerosis ms brain infection dementia traumatic brain injury stroke rank retention rates asms validated comparison published randomized control trials identified optimal stratification brain disease quantified potential improvement patients received optimal asmresults using optimal stratification brain disease potential improvement retention rate percentage points ms 20 brain infection 21 dementia 14 trauma 21 stroke 14 epilepsy trauma levetiracetam highest retention rate 80 95 confidence interval ci 6589 exceeding commonly prescribed asm carbamazepine p 04 epilepsy dementia lamotrigine 77 95 ci 6884 levetiracetam 74 95 ci 6879 higher retention rates carbamazepine p 006 p 01 respectively significance conclude personalized asm selection improve retention rates national registers potential big data sources personalized medicine epilepsypmid34245010 doi101111 epi16987,0.0
exercise multimodal diseasemodifying medicine systemic sclerosis introduction global fellowship rehabilitation exercise systemic sclerosis gforss best pract res clin rheumatol 2021 jun 30101695 doi 101016 jberh2021101695 online ahead printabstractsystemic sclerosis ssc heterogeneous multisystem autoimmune disease whereby main pathological drivers disability damage vascular injury inflammatory cell infiltration fibrosis mechanisms result diffuse diverse impairments arising ischemic circulatory dysfunction leading painful skin ulceration calcinosis neurovascular aberrations hindering gastrointestinal gi motility progressive painful incapacitating immobilizing effects inflammatory fibrotic effects lungs skin articular periarticular structures muscle sscrelated impairments impede routine activities daily living adls disrupt three critical life areas work family social leisure also impact psychological wellbeing physical activity exercise globally recommended however connective tissue diseases guidance carries greater impact inflammatory disease manifestations recovery cardiovascular health exercise myogenic vascular phenomena naturally targets key pathogenic drivers downregulating multiple inflammatory fibrotic pathways serum tissue increasing circulation vascular repair gforss global fellowship rehabilitation exercise systemic sclerosis recognizes scientific basis advocates education research exercise systemic targeted ssc diseasemodifying treatment overview biophysiological mechanisms physical activity exercise herein imparted patients clinicians researchers applied ssc disease mechanisms manifestations impairment preliminary guidance exercise ssc research agenda current state research outcome measures set forthpmid34217607 doi101016 jberh2021101695,1.0
updated review versatile role chrysin neurological diseases chemistry pharmacology drug delivery approaches biomed pharmacother 2021 jul 16 141111906 doi 101016 jbiopha2021111906 online ahead printabstractneurological diseases responsible large number morbidities mortalities world flavonoids phytochemicals possess various healthpromoting impacts chrysin natural flavonoid isolated diverse fruits vegetables even mushrooms several pharmacological activities comprising antioxidant antiinflammatory antiapoptotic anticancer neuroprotective effects current study designed review relationship chrysin administration neurological complications discussing feasible mechanism signaling pathways herein mentioned sources pharmacological properties chemistry drug delivery systems associated chrysin pharmacotherapy role chrysin discussed depression anxiety neuroinflammation alzheimers disease parkinsons disease huntingtons disease epilepsy cerebral ischemia spinal cord injury neuropathy multiple sclerosis guillainbarr syndrome findings indicate chrysin protective effects neurological conditions modulating oxidative stress inflammation apoptosis animal models however studies done clear neuroprotective effects chrysinpmid34328092 doi101016 jbiopha2021111906,1.0
influence interferon beta1b gut microbiota composition patients multiple sclerosis neurologia engl ed 2021 sep 36 7 495503 doi 101016 jnrleng202005006 epub 2020 may 31abstractintroduction association gut microbiota animal models multiple sclerosis well established however studies humans scarcemethods performed descriptive crosssectional study comparing relative composition gut microbiota 30 patients multiple sclerosis 15 treated interferon 1b 15 receiving treatment 14 healthy controls using next generation sequencingresults patients multiple sclerosis controls showed differences proportion euryarchaeota firmicutes proteobacteria actinobacteria lentisphaerae phyla 17 bacterial species specifically found significant differences proportion firmicutes actinobacteria lentisphaerae 6 bacteria species controls untreated patients however differences disappeared compared treated patients untreated patients showed significant reduction proportion prevotella copri compared controls bacteria significantly abundant patients treated interferon 1b untreated patients levels resembling observed healthy control groupconclusion observed differences gut microbiota composition patients multiple sclerosis controls patients treated treated interferon 1b cases differences observed treated patients healthy controls particularly p copri levels suggests clinical improvements observed patients multiple sclerosis receiving interferon 1b may result effect drug gut microbiota longitudinal functional studies necessary establish causal relationshippmid34537163 doi101016 jnrleng202005006,0.0
altered sensorimotor integration multiple sclerosis combined neurophysiological functional mri study clin neurophysiol 2021 jun 25 132 9 21912198 doi 101016 jclinph202105028 online ahead printabstractobjective explore whether abnormal thalamic restingstate functional connectivity rsfc contributes altered sensorimotor integration hand dexterity impairment multiple sclerosis ms methods evaluate sensorimotor integration recorded kinematic features index finger abductions somatosensory temporal discrimination threshold stdt testing 36 patients relapsingremitting ms 39 healthy controls hc participants underwent multimodal 3t structural functional mri protocolresults patients lower index finger abduction velocity stdt testing compared hc thalamic rsfc precentral postcentral gyri supplementary motor area sma insula basal ganglia higher patients hc intrathalamic rsfc thalamic rsfc caudate insula bilaterally lower patients hc finger movement velocity positively correlated intrathalamic rsfc negatively correlated thalamic rsfc precentral postcentral gyri sma putamenconclusions abnormal thalamic rsfc possible substrate altered sensorimotor integration ms high intrathalamic rsfc facilitating finger movements increased thalamic rsfc basal ganglia sensorimotor cortex contributing motor performance deteriorationsignificance combined study thalamic functional connectivity upper limb sensorimotor integration may useful identifying patients can benefit early rehabilitation prevent upper limb motor impairmentpmid34293529 doi101016 jclinph202105028,0.0
early treatment delays longterm disability accrual rrms results bmsd network mult scler 2021 apr 2613524585211010128 doi 101177 13524585211010128 online ahead printabstractbackground optimal timing treatment starts achieving best control longterm disability accumulation multiple sclerosis ms still definedobjective aim study estimate optimal time start diseasemodifying therapies dmts prevent longterm disability accumulation ms using pooled dataset big multiple sclerosis data bmsd networkmethods multivariable cox regression models adjusted time first treatment start disease onset quintiles used mitigate impact potential biases set pairwise propensity score ps matched analyses performed first quintile including patients treated within 12 years onset used referenceresults cohort 11 871 patients median followup treatment start 132 years analyzed 3 12month confirmed disability worsening event irreversible expanded disability status scale edss 40 60 scores reached 7062 595 4138 349 3209 311 1909 165 patients respectively risk reaching disability outcomes significantly lower p 00004 first quintile patients groupconclusion realworld data bmsd demonstrate dmts commenced within 12 years disease onset reduce risk disability accumulation long termpmid33900144 doi101177 13524585211010128,0.0
safety patientreported wellbeing physicianreported assessment walking ability patients multiple sclerosis prolongedrelease fampridine treatment routine clinical practice results liberate study cns drugs 2021 jul 28 doi 101007 s4026302100840x online ahead printabstractbackground prolongedrelease fampridine prfam 10mg tablet twice daily approved pharmacological treatment improvement walking ability adults multiple sclerosis ms liberate assessed safety effectiveness prfam realworldobjectives aim study collect additional safety data including incidence rate seizures adverse events aes interest patients ms taking prfam routine clinical practice including patients aged 65 years preexisting cardiovascular risk factors objectives included change time patientreported evaluation physical psychological impact ms taking prfam change time physicianreported assessment walking ability ms patients taking prfammethods patients ms newly prescribed prfam recruited 201 sites 13 countries demographic safety data collected enrolment 12 months physicianrated clinical global impression improvement cgii scores walking ability multiple sclerosis impact scale29 msis29 assessedresults safety analysis included 4646 patients 35348 patientyears exposure median range age 526 2185 years 873 65 years 657 women treatmentemergent aes teaes reported 2448 527 patients serious teaes reported 279 60 patients 37 1 experienced treatmentemergent serious aes tesaes considered related prfam aes special interest aesi occurred 1799 387 patients serious aesi 128 28 patients seventeen 1 patients experienced actual events seizure overall 1158 249 patients discontinued treatment due lack efficacy 12 months greater proportion patients ontreatment improvement baseline cgii walking ability versus discontinued 61 vs 11 p 0001 msis29 physical impact score improved significantly patients ontreatment 12 months versus discontinued mean change baseline 12 months 999 vs 034 points p 0001 results similar msis29 psychological impactconclusion new safety concerns identified realworld study suggesting routine riskminimization measures effective cgii msis29 scores 12 months treatment prfam treatment show clinical benefits consistent previously reportedtrial registration clinicaltrialsgov nct01480063pmid34322853 doi101007 s4026302100840x,1.0
validity urinary symptom questionnaires people neurogenic bladder usqnb void use indwelling catheters spinal cord 2021 aug 4 doi 101038 s4139302100666w online ahead printabstractstudy design descriptive psychometrics study objectives neurogenic lower urinary tract dysfunction nlutd neurogenic bladder common disruptive condition individuals spinal cord injury sci disease including multiple sclerosis ms team developed patientcentered instruments urinary symptoms specific patients nlutd across bladder management methods validity evidence needed support use two new instruments urinary symptom questionnaires people neurogenic bladder usqnb manage bladder indwelling catheters idc void v setting online surveys completed individuals united states nlutd due either sci ms manage bladder indwelling catheters sci n 306 ms n 8 voiding sci n 103 ms n 383 total n 381 usqnbidc respondents five control groups 351 usqnbv respondents four control groups contributed convergent divergent validity evidencemethods data collected online estimate key aspects psychometric validity content reflection construct measured face recognizability contents representing construct measured structural extent instrument captures recognizable dimensions construct measured divergent convergent validity evidence derived multiple control groups evidence criterion validity derived attribution item experience utiresults evidence face content criterion convergent divergent validity compiled instrumentconclusions instruments demonstrate adequate multidimensional validity evidence recommend use decisionmaking patients clinicians researcherspmid34349234 doi101038 s4139302100666w,0.0
aging neuroinflammation changes immune cell responses axon integrity motor function viral model progressive multiple sclerosis aging cell 2021 aug 6e13440 doi 101111 acel13440 online ahead printabstractalthough aggravated multiple sclerosis ms disability reported aged patients aging impact immune cells remodeling within cns well understood investigated influence aging immune cells neuroinflammatory neurodegenerative processes occur wellestablished viral model progressive ms found anomalous presence cd4+ t cd8+ t b cells cells myeloid lineage cns old sham mice whereas blunted cellular innate adaptive immune response observed theilers murine encephalomyelitis virus tmev infected old mice microglia macrophages show opposite cns viral responses regarding cell counts old mice furthermore enhanced expression programmed deathligand 1 pdl1 found microglia isolated old tmevinfected mice isolated cns macrophages immunocytochemical staining microglial cells confirms differences young old mice agerelated axonal loss integrity mouse spinal cord found tmev mice less marked neurodegenerative process present old sham mice compared young sham mice tmev sham old mice also display alterations innate adaptive immunity spleen compared young mice study supports need new adapted pharmacological strategies ms elderly patientspmid34355492 doi101111 acel13440,0.0
clinical perspectives molecular pharmacological attributes anticd20 therapies multiple sclerosis cns drugs 2021 aug 9 doi 101007 s40263021008438 online ahead printabstractanticd20 therapies demonstrated considerable efficacy treatment relapsing multiple sclerosis constituting highefficacy treatment approach reducing relapse risk mitigating disability progression therapies shown strongly deplete circulating b cells small subsets cd3+ cd4 cd8 t cells express low levels cd20 clinical profiles various anticd20 monoclonal antibodies used treating multiple sclerosis welldescribed literature greater understanding implications distinct molecular pharmacological attributes needed review focus four anticd20 monoclonal antibodiesrituximab ocrelizumab ofatumumab ublituximabthat currently used approved latestage clinical development treatment multiple sclerosis provide clinical perspectives potential implications differences molecular structures target epitopes dosing regimens mechanisms impact bcell depletion reconstitution immunogenicity administrationrelated reactions infection riskspmid34370283 doi101007 s40263021008438,0.0
circular rna circinpp4b acts sponge mir30a regulate th17 cell differentiation progression experimental autoimmune encephalomyelitis cell mol immunol 2021 aug 6 doi 101038 s4142302100748y online ahead printabstractcircular rnas circrnas regulate gene expression participate various biological pathological processes however little known effects specific circrnas t helper cell 17 th17 differentiation related autoimmune diseases multiple sclerosis ms using transcriptome microarray analysis different stages experimental autoimmune encephalomyelitis eae identified eae progressionrelated circinpp4b showed upregulated expression th17 cells mice eae th17 differentiation vitro silencing circinpp4b inhibited th17 differentiation alleviated eae characterized less demyelination th17 infiltration spinal cord mechanistically circinpp4b served sponge directly targeted mir30a regulate th17 differentiation furthermore circinpp4b levels associated developing phases clinical relapsingremitting ms patients results indicate circinpp4b plays important role promoting th17 differentiation progression eae targeting mir30a provides potential diagnostic therapeutic target th17mediated mspmid34363030 doi101038 s4142302100748y,1.0
longterm disease stability assessed expanded disability status scale patients treated cladribine tablets 35 mg kg relapsing multiple sclerosis exploratory post hoc analysis clarity clarity extension studies adv ther 2021 aug 9 doi 101007 s1232502101865w online ahead printabstractintroduction cladribine tablets treating multiple sclerosis orally clarity study cladribine tablets significantly reduced relapse rates improved findings magnetic resonance imaging versus placebo patients relapsing multiple sclerosis clarity extension study treatment cladribine tablets 2 years followed placebo 2 years produced similar clinical benefits 4 years cladribine tablets objective exploratory post hoc analysis evaluate longterm disease stability assessed expanded disability status scale edss score treatment cladribine tabletsmethods patients enrolled clarity extension previously randomized cladribine tablets 35 mg kg clarity study included post hoc analysis two treatment groups investigatedpatients randomized cladribine tablets 35 mg kg clarity thereafter randomized placebo clarity extension cp35 group cladribine tablets 35 mg kg clarity extension cc7 group treatment group edss scores 6month intervals edss score improvement worsening year time 3 6month confirmed edss progression assessed clarity baseline 5 years followup including variable bridging interval studies analyses descriptive statistical comparisons performed betweentreatment group differencesresults median 95 confidence interval ci edss score patients cp35 group 5 years 25 2035 compared 30 2535 baseline cc7 group median edss score 95 ci 5 years 20 2030 compared 25 2530 baseline year 5 cp35 group based changes minimum score year edss score stability observed 539 patients improvement 213 worsening 247 cc7 group edss score remained stable 661 improved 181 worsened 158 patients 70 patients treatment groups show 3 6month confirmed edss progression 5 years clarity baselineconclusions findings confirm longterm beneficial effects disability afforded either recommended dose cladribine tablets 4 years cumulative dose 35 mg kg higher cumulative dosetrial registration clinicaltrialsgov nct00213135 clarity nct00641537 clarity extension pmid34370275 doi101007 s1232502101865w,0.0
gait parameters improve botulinum toxin injections post stroke patients prospective study toxicon 2021 aug 9s00410101 21 002129 doi 101016 jtoxicon202108001 online ahead printabstractthe intramuscular injection botulinum toxin one efficient ways treat localized spasticity patients suffering central nervous system lesions like stroke cerebral palsy multiple sclerosis gait analysis based kinetics kinematics recognized way measurement effect intramuscular injection botulinum toxin spastic patients suffering chronic stroke aim study provide evidence beneficial effect botulinum toxin characteristics gait pattern patients suffering chronic stroke thirteen patients spasticity due chronic stroke included protocol treated botulinum toxin injections lower extremity patients evaluated injection well one month botulinum injection foot pressure sensitive walkway power plate readings seven inertial measurements units recorded spatiotemporal specific parameters walking spasticity measured according modified ashworth scale spatiotemporal parameters motion analysis balance improved patients botulinum toxin injection one parameter normal hemiplegic step length reached statistical significant improvement p003 moreover modified ashworth score statistically improved post injection p0001 conclusion use botulinum toxin injections beneficial post stroke patients depicted gait parameters change accompanies spasticity reductionpmid34384786 doi101016 jtoxicon202108001,0.0
economic evaluation cladribine tablets patients high disease activityrelapsingremitting multiple sclerosis kingdom saudi arabia value health reg issues 2021 aug 20 25189195 doi 101016 jvhri202103007 online ahead printabstractobjective cladribine tablets first shortcourse oral treatment approved high disease activity relapsingremitting multiple sclerosis hdarrms across various countries analysis assessed costeffectiveness introducing cladribine tablets treatment option patients high disease activity compared hdarrms therapies kingdom saudi arabia ksa methods costeffectiveness model adapted ksa payers perspective data models adaptation retrieved literature validated key opinion leaders comparators considered model alemtuzumab dimethyl fumarate fingolimod interferon beta1a subcutaneous intramuscular beta1b natalizumab teriflunomide sensitivity analysis also performed assess robustness analysisresults costeffectiveness results showed cladribine tablets dominant strategy ie less costly effective versus comparators incremental cost qualityadjusted lifeyears gained largely driven drug acquisition cost delayed expanded disability status scale progression respectively cladribine tablets showed 81 100 probability costeffective threshold saudi riyal 225 326 per qualityadjusted lifeyears gained different comparatorsconclusions cladribine tablets dominant treatment option patients hdarrms payer perspective ksapmid34425468 doi101016 jvhri202103007,0.0
paradigm shifts early initiation highefficacy diseasemodifying treatment multiple sclerosis mult scler 2021 sep 27 10 14731476 doi 101177 13524585211033190no abstractpmid34472985 doi101177 13524585211033190,0.0
interactions lipids lipoproteins apolipoproteins bloodbrain barrier pharm res 2021 sep 13 doi 101007 s11095021030986 online ahead printabstractlipids lipoproteins diverse group substances interactions bloodbrain barrier bbb similarly diverse lipoproteins high density lipoprotein hdl apolipoprotein apo ai apoj free fatty acids triglycerides cross bbb whereas others apoe forms cholesterol can cross bbb others lipids can effects bbb preservation function hdl may protect bbb multiple sclerosis cholesterol can disrupt bbb triglycerides inhibit transport leptin across bbb activation hypothalamic leptin receptor apoe associated many effects bbb specific isoform apoe4 detrimental effects summary diverse ways lipids lipoproteins apolipoproteins interact bbb important health diseasepmid34518942 doi101007 s11095021030986,0.0
strategies maintaining dynamic balance persons neurological disorders overground walking proc inst mech eng h 2021 jun 119544119211023624 doi 101177 09544119211023624 online ahead printabstractmaintaining stable gait requires dynamic balance control can altered persons multiple sclerosis ms stroke st parkinsons disease pd understanding strategy center mass com positioning adopted patients walking important able program treatments aimed improving gait control preventing falls fortyfour persons mildtomoderate neurological disorder 20 ms 14 st 10 pd underwent clinical examination gait analysis ten healthy subjects hs walking matched speed provided normative data dynamic balance assessed using margin stability mos calculated distance extrapolated center pressure extrapolated com midstance mos values lower limbs calculated patients compared speedmatched values hs persons neurological disorder showed increased mos mediolateral direction respect hs withingroup comparison analysis showed symmetry lower limbs hs mean 95ci mm dominant vs nondominant limb 433 319546 vs 429 288569 pd less affected vs affected limb 711 598825 vs 725 585866 significant asymmetry found ms 544 464624 vs 811 712911 st 521 426617 vs 747 628866 participants history falls comparable among pd ms st groups mos frontal plane showed strong correlation records objective assessment mos revealed pathologyspecific strategies showing different impacts ms st pd ability control com information manage balance limbs gait mos evaluation will provide useful information address tailored rehabilitation program monitor disease progressionpmid34112028 doi101177 09544119211023624,0.0
cannabinoids skin diseases hair regrowth j cosmet dermatol 2021 aug 7 doi 101111 jocd14352 online ahead printabstractthe use cannabis skin diseases hair regrowth preliminary stagelegalization many countries approved cannabis medical use however four countries canada uruguay south africa georgia legalized medical recreational purposesthe endocannabinoid system endocannabinoid system may maintain skin homeostasis two notable endocannabinoids include 2arachidonoylglycerol 2ag narachidonoylethanolamine aea routes administration pharmacokinetics topical cannabinoids can avoid firstpass metabolism reduce respiratory side effects however high hydrophobicity cannabinoids may hinder percutaneous absorptionskin disorders hair growth human clinical studies suggest cannabinoids may used eczema acne pruritus systemic sclerosis treatment cannabidiol cbd may enhance hair growth via multiple mechanismssafety topical cannabis may cause mild side effects pruritus burning erythema stinging relatively safer inhalation oral cannabis cannabis use may associated allergic symptoms reduced immune response live vaccinationcannabinoids practice despite growing interest dermatologists cautious prescribing cannabinoids due insufficient clinical data efficacy safetypmid34363728 doi101111 jocd14352,0.0
analysis diagnostic pathway delay patients amyotrophic lateral sclerosis valencian community neurologia engl ed 2021 sep 36 7 504513 doi 101016 jnrleng201803023 epub 2020 jun 3abstractintroduction amyotrophic lateral sclerosis als insidious clinically heterogeneous neurodegenerative disease associated diagnostic delay approximately 12 months study conducted date analysed diagnostic pathway spainmethods gathered data variables related diagnostic pathway delay patients diagnosed als october 2013 july 2017results study included 143 patients als 57 men 68 spinal onset patients diagnosed public centres 86 cases private centres 14 mean diagnostic delay 131 months median 117 patients examined neurologists mean time 79 months symptom onset diagnosis made 52 months later half patients underwent unnecessary diagnostic tests multiple electrophysiological studies diagnosis established diagnostic delay longer cases spinal onset p008 due onset disease lower limbs differences found public private healthcare systems p897 conclusions diagnostic delay als spain similar neighbouring countries seems depend diseaserelated factors healthcare system patients lowerlimb onset als constitute greatest diagnostic challenge misdiagnosis frequent partly attributable incorrect approach erroneous interpretation electrophysiological studies specific training programmes neurologists general neurophysiologists early referral reference centres may help reduce diagnostic delaypmid34537164 doi101016 jnrleng201803023,0.0
nobiletin suppresses development experimental autoimmune encephalomyelitis mediated modulation t helper 17 cell differentiation j clin biochem nutr 2021 sep 69 2 145150 doi 103164 jcbn20178 epub 2021 mar 25abstractmultiple sclerosis organspecific autoimmune disease targets myelin antigen central nervous system nobiletin dietary polymethoxylated flavonoid found citrus fruits study investigated nobiletin affects disease state immune responses myelin oligodendrocyte glycoprotein experimental autoimmune encephalomyelitis mice nobiletin administered orally 14 days immunization end experiment clinical scores determined production levels interleukin17a interferon measured culture supernatant splenocytes stimulated myelin oligodendrocyte glycoprotein addition flow cytometric analysis performed examine effect nobiletin t cell differentiation vitro administration nobiletin significantly decreased clinical score interleukin17a production splenocytes furthermore vitro analysis showed nobiletin significantly suppressed th17 cell differentiation interleukin17a production dosedependent manner results suggest nobiletin attenuates experimental autoimmune encephalomyelitis severity modulation th17 cell differentiationpmid34616106 pmcpmc8482387 doi103164 jcbn20178,1.0
defective complex iii mitochondrial respiratory chain due novel variant cyc1 gene masquerades acute demyelinating syndrome leber hereditary optic neuropathy mitochondrion 2021 jul 9s15677249 21 000866 doi 101016 jmito202107001 online ahead printabstractcomplex iii ciii third five mitochondrial respiratory chain complexes residing mitochondrial inner membrane assembly 10 subunits encoded nuclear dna one mitochondrial dna result functional ciii transfers electrons ubiquinol cytochrome c deficiencies ciii among least investigated mitochondrial disorders thus clinical spectrum patients mutations ciii well defined report 10yearold girl born consanguineous iranian parents presenting recurrent visual loss episodes optic nerve contrast enhancement brain imaging reminiscent acquired demyelination syndrome ie optic neuritis multiple sclerosis ultimately confirmed novel homozygous missense variant unknown significance c949ct p arg317trp cyc1 gene nuclear dna subunit complex iii mitochondrial chain sanger sequencing confirmed segregation variant disease family effect variant protein structure shown insilico findings expand clinical spectrum due defects cyc1 gene also highlight mitochondrial respiratory chain disorders considered potential differential diagnosis children present unusual patterns acquired demyelination syndromes ads addition results support hypothesis mitochondrial disorders might overlapping presentation adspmid34252606 doi101016 jmito202107001,1.0
interleukin10 promoter ccr5 polymorphisms iranian azari population multiple sclerosis iran j immunol 2021 sep 18 3 211215 doi 1022034 iji2021838831634abstractbackground changes expression cytokines result single nucleotide polymorphisms snps can affect occurrence multiple sclerosis ms objective investigate frequency interleukin10 il10 1082 g rs1800896 ccr5delta32 genotypes susceptibility ms iranian azari populationmethods il101082 g snp ccr5delta32 152 patients suffering ms 242 healthy nonrelatives genotyped allele specificpcr simple pcr methods respectivelyresults frequencies aa 376 ag 559 genotypes il101082 significantly high control p 0021 ms patients p 0015 respectively statistical difference significant difference ccr5 gene based possession wild wild wild del32 genotypes ms patients control group del32 del32 genotype seen investigated groups tobacco cigarettes hookahs consumption higher among ms patients p0004 potential raise risk ms individuals family significant relation frequency different genotypes il101082 ccr5 ms disease prevalent among people lowincome p00001 conclusion finding conclude possible role aa genotype il10 1082 protective factor studied patientspmid34596589 doi1022034 iji2021838831634,0.0
objective medication adherence persistence people multiple sclerosis systematic review metaanalysis metaregression j manag care spec pharm 2021 sep 27 9 12731295 doi 1018553 jmcp20212791273abstractbackground medication adherence critical realization pharmacotherapy benefits reduced healthcare expenditure studies shown 60 people multiple sclerosis ms experience suboptimal medication adherence associated poorer health outcomes subsequent discontinuation current systematic review reported objectively measured adherence discontinuation rates selfadministered oral injectable diseasemodifying therapies dmts objectives identify whether people ms introduction oral dmts improved medication adherence compared injectable dmts secondary aim report synthesized objectively measured medication adherence persistence rates oral injectable dmts ms across varying study durations methods literature searches conducted pubmed web science scopus psycinfo inclusion criteria limited english peerreviewed objective selfadministered dmt articles published july 1993 december 2019 publications reporting combined intravenous selfadministered dmt data account dmt switching discontinuation rates excluded data synthesized observation lengths ranging less 8 months greater 36 months metaanalysis metaregression undertaken oral injectable 12month adherence discontinuation data results total 61 articles included 46 articles examined adherence 26 examined discontinuation twelvemonth adherence ranged 530 892 oral n 7 470 774 injectable dmts n 7 results metaanalysis metaregression show significantly higher pooled mean medication possession ratio mpr adherence oral dmts 910 compared injectable dmts 770 12 months 0146 95 ci 0263 0029 results indicate major asymmetry across studies lfk index 518 proposing presence significant publication bias mean discontinuation 12 months 105 333 oral n 7 152 508 injectable dmts n 10 metaanalysis results indicating presence significant heterogeneity i2 injectable 995 i2 oral 931 studies included subgroup however appreciable difference mean discontinuation rates across groups injectable 27 95 cl 190340 oral 24 95 ci 170310 found conclusions medication adherence oral dmts suggests significant improvement compared adherence injectable dmts significant difference discontinuation rates oral injectable dmts found oral dmt adherence persistence studies limited given relatively recent introduction suboptimal medication adherence discontinuation issues remain present oral injectable dmts future studies benefit improved consistency methodology comparable adherence persistence definitions disclosures authors receive funding study mardan hussain nothing disclose grech reports grants merck pharmaceutical outside submitted work allan reports grants received merck pharmaceutical outside submitted work allan holds advisory board consulting positions merck advisory board positions bristol myers squibb novartis monash institute neurological diseases receives consulting feespmid34464209 doi1018553 jmcp20212791273,0.0
pediatric spinal cord diseases pediatr rev 2021 sep 42 9 486499 doi 101542 pir2020000661abstractspinal cord diseases pediatric patients highly variable terms presentation pathology prognosis differ respect adult equivalents common diseases autoimmune ie multiple sclerosis acute disseminated encephalomyelitis acute transverse myelitis congenital ie dysraphism spina bifida split cord malformation tethered cord syndrome tumor ie juvenile pilocytic astrocytoma ependymoma hemangioblastoma vascular ie cavernous malformations arteriovenous malformations dural arteriovenous fistulas nature require niche treatment paradigm prognosis furthermore presentation different spinal cord diseases children can difficult discern without epidemiologic imaging data interpretation data crucial facilitating timely accurate diagnosis correspondingly aim review highlight pertinent features common spinal cord diseases pediatric populationpmid34470868 doi101542 pir2020000661,0.0
multiple sclerosis treatment blunts sarscov2 antibody response nat rev neurol 2021 aug 9 doi 101038 s41582021005513 online ahead printno abstractpmid34373633 doi101038 s41582021005513,0.0
pharmacologic activities phytosteroids inflammatory diseases mechanism action therapeutic potentials phytother res 2021 may 6 doi 101002 ptr7138 online ahead printabstractnatural products derivatives known useful treating numerous diseases since ancient times high therapeutic potentials use different medicinal plants possible treat varied inflammationmediated chronic diseases among natural products phytosteroids emerged promising compounds mostly diverse pharmacological activities currently available medications exert numerous systemic toxicities including hypertension immune suppression osteoporosis metabolic abnormalities thus research phytosteroids subside complications significant importance study information phytosteroids types actions inflammation allergic complications collected systematic survey literature several scientific search engines literature review suggested phytosteroids exhibit antiinflammatory action via different modes transrepression selective cox2 enzymes also silico admet analysis carried available phytosteroids uncover pharmacokinetic properties analysis shown eight compounds withaferin stigmasterol sitosterol guggulsterone diosgenin sarsasapogenin physalin dioscin isolated medicinal plants show similar pharmacokinetic properties compared dexamethasone commercially available glucocorticoid phytosteroids useful treatment inflammatory diseases rheumatoid arthritis inflammatory bowel diseases multiple sclerosis asthma cardiovascular diseases thus systematic research required explore potent phytosteroids lesser side effects might substitute current medicationspmid33957012 doi101002 ptr7138,0.0
tumefactive demyelination updated perspectives diagnosis management expert rev neurother 2021 aug 23 doi 101080 1473717520211971077 online ahead printabstractintroduction tumefactive demyelination td can challenging scenario clinicians due difficulties distinguishing conditions neoplasm infection managing consequences acute lesions deciding upon appropriate longer term treatment strategyareas covered authors review literature regarding td covering clinicradiological features association multiple sclerosis ms differential diagnosis neuroinflammatory noninflammatory mimicking disorders emphasis atypical forms demyelination including acute disseminated encephalomyelitis adem mog antibodyassociated demyelination mogad neuromyelitis spectrum disorders nmosd also review latest acute longterm treatment tdexpert opinion important underlying cause td determined whenever possible guide management approach differs different demyelinating inflammatory conditions improved neuroimaging advances serum csf biomarkers one day allow early accurate diagnosis td leading better outcomes patientspmid34424129 doi101080 1473717520211971077,1.0
quality life measures pediatric multiple sclerosis systematic review metaanalysis dev med child neurol 2021 mar 26 doi 101111 dmcn14870 online ahead printabstractaim identify generic measures used measure quality life qol pediatric multiple sclerosis research estimate overall score children adolescents pediatric multiple sclerosis compare scores scores typically developing children adolescentsmethod systematic search conducted four databases studies included sample children pediatric demyelinating disorders selfreported qol healthrelated quality life hrqol measures results reported mean age sample 21 years quality included articles appraised using strengthening reporting observational studies epidemiology strobe checklist mixed methods appraisal tool checklist metaanalysis also conductedresults total 12 fulltext articles included content analysis showed many components qol included measures seven studies included metaanalysis metaanalyzed score 757 95 confidence interval 712803 pooled standard deviation 166 scores typically developing children children pediatric multiple sclerosis similarinterpretation measures assessed hrqol qol development conditionspecific measure qol children adolescents pediatric multiple sclerosis make important contribution fieldpmid33769574 doi101111 dmcn14870,1.0
approach optic neuritis update indian j ophthalmol 2021 sep 69 9 22662276 doi 104103 ijoijo_3415_20abstractover past years remarkable development area optic neuritis discovery new antibodies improved understanding pathology disease antiaquaporin4 antibodies antimyelin oligodendrocytes antibodies now considered distinct entities optic neuritis specific clinical presentation neuroimaging characteristics treatment options course disease similarly substantial change treatment optic neuritis earlier limited steroids interferons development new immunosuppressant drugs monoclonal antibodies reduced relapses improved prognosis optic neuritis well associated systemic disease review article tends provide update approach management optic neuritispmid34427197 doi104103 ijoijo_3415_20,1.0
comprehensive framework navigating patient care systemic sclerosis global response need improving practice diagnostic preventive strategies ssc best pract res clin rheumatol 2021 sep 15101707 doi 101016 jberh2021101707 online ahead printabstractsystemic sclerosis ssc lethal rheumatologic conditions cause death 50 ssc cases led pulmonary fibrosis followed pulmonary hypertension scleroderma renal crisis src multiple preventable treatable sscrelated vascular cardiac gastrointestinal nutritional musculoskeletal complications can lead disability death vascular injury subsequent inflammation transforming irreversible fibrosis permanent damage characterizes ssc organ involvement often present early disease course ssc requires careful historytaking vigilance screening detect inflammation potentially reversible provided treatment intensity quells inflammation immune mechanisms ssc phenotype opportunities early treatment prone underutilized especially slowly progressive phenotypes contrast severe progressive ild indolently accrue irreversible organ damage resulting laterstage lifelimiting complications pulmonary hypertension cardiac involvement malnutrition single ssc patient visit often requires much physician staff time organization vigilance direct management multiple organ systems compared rheumatic pulmonary diseases efficiency efficacy comprehensive ssc care enlists trending symptoms biodata financial sustainability ssc care benefits understanding insurance reimbursement health system allocation policies complex patients sharing care recognised ssc centers local cardiology pulmonary rheumatology gastroenterology colleagues may prevent complications poor outcomes providing support local specialists scleroderma specialists offer practical framework tools facilitate optimal comprehensive sustainable approach ssc care improved health outcomes ssc relies upon recogntion management extent possible prevention ssc treatmentrelated complicationspmid34538573 doi101016 jberh2021101707,0.0
research advance pharmacological effects astragalosides nervous system diseases zhongguo zhong yao za zhi 2021 sep 46 18 46744682 doi 1019540 jcnkicjcmm20210610704abstractastragali radix traditional chinese herbal medicine long history functions tonifying qi promoting urination granulation astragalosides main effective components astragali radix 40 triterpenoid saponins obtained astragalus membranaceus related plants mainly including astragalosides isoastragalosides acetylastragalosides soyasaponins astragalosides wide range biological activities immunomodulation antioxidation neuroprotection nervous system diseases seriously affect peoples quality life threaten human physical mental health impose burden families society natural drugs astragalosides good preventive therapeutic effects central nervous system diseases paper reviews main pharmacological effects mechanisms astragalosides treatment multiple sclerosis parkinsons disease alzheimers disease cerebral ischemic stroke proposes research prospects potential problems aiming provide reference clinical application basic research astragalosidespmid34581075 doi1019540 jcnkicjcmm20210610704,0.0
pharmacogenetic predictors response interferon beta therapy multiple sclerosis mol neurobiol 2021 jun 24 doi 101007 s12035021024542 online ahead printabstractfirstline therapy interferon beta ifn involved gene expression modulation immune response widely used multiple sclerosis however 3050 patients respond optimally variants cblb ctss gria3 oas1 tnfrsf10a genes proposed contribute variation individual response purpose study evaluate influence gene polymorphisms ifn response relapsingremitting multiple sclerosis rrms patients cblb rs12487066 gria3 rs12557782 ctss rs1136774 oas1 rs10774671 tnfrsf10a rs20576 polymorphisms analysed taqman 137 rrms patients response ifn change expanded disability status scale edss 24 months evaluated using multivariable logistic regression analysis carriers least one copy c allele ctssrs1136774 better response ifn p 00423 294 ci95 103 840 carriers tt genotype tnfrsf10ars20576 higher probability maintaining edss stable 24 months ifn treatment p 00251 571 ci95 139 3175 influence cblb rs12487066 oas1 rs10774671 gria3 rs12557782 gene polymorphisms variation individual response ifn shown results suggest tnfrsf10ars20576 ctssrs1136774 gene polymorphisms influence response ifn 24 months cblb rs12487066 oas1 rs10774671 gria3 rs12557782 gene polymorphisms effect variation individual response ifnpmid34169444 doi101007 s12035021024542,0.0
synaptic blocker botulinum toxin decreases density complexity oligodendrocyte precursor cells adult mouse hippocampus j neurosci res 2021 may 29 doi 101002 jnr24856 online ahead printabstractoligodendrocyte progenitor cells opcs responsible generating oligodendrocytes myelinating cells cns lifelong myelination promoted neuronal activity essential neural network plasticity learning opcs known contact synapses proposed neuronal synaptic activity turn regulates behavior examine adult performed unilateral injection synaptic blocker botulinum neurotoxin bont hippocampus adult mice confirm bont cleaves snap25 ca1 hippocampus proven block neurotransmission notably bont significantly decreased opc density caused shrinkage determined immunolabeling opc marker ng2 furthermore bont resulted overall decrease number opc processes well decrease lengths branching frequency data indicate synaptic activity important maintaining adult opc numbers cellular integrity relevant pathophysiological scenarios characterized dysregulation synaptic activity agerelated cognitive decline multiple sclerosis alzheimers diseasepmid34051113 doi101002 jnr24856,1.0
levels serine protease htra1 cerebrospinal fluid correlate progression disability multiple sclerosis j neurol 2021 mar 4 doi 101007 s00415021104897 online ahead printabstractbackground high temperature requirement serine protease a1 htra1 degrades extracellular matrix molecules ecms growth factors interacts several proteins implicated multiple sclerosis ms previously linked diseaseobjective investigate levels htra1 cerebrospinal fluid csf different subtypes ms brain tissuemethods using elisa htra1 levels compared csf untreated patients relapsingremitting ms rrms n 23 secondary progressive ms spms n 26 healthy controls hcs n 26 effect disease modifying therapies dmts examined patient groups cellular distribution human brain studied using immunochemistry oligointernode database based singlenuclei rna expression mapresults htra1 increased rrms spms compared hcs dmt decreased htra1 levels types ms using roc analysis htra1 cutoffs discriminate hcs rrms patients 100 specificity 826 sensitivity brain htra1 expressed glia neuronsconclusion htra1 promising csf biomarker ms correlating disease disability progression cell species normal diseased cns express htra1 expression pattern reflect pathological processes involved ms pathogenesispmid33661357 doi101007 s00415021104897,0.0
review possible therapies multiple sclerosis mol cell biochem 2021 apr 22 doi 101007 s1101002104119z online ahead printabstractmultiple sclerosis ms autoimmune chronic inflammatory disease central nervous system wide range symptoms like executive function defect cognitive dysfunction blurred vision decreased sensation spasticity fatigue symptoms neurological disease characterized destruction bloodbrain barrier loss myelin damage neurons result immune cells crossing bloodbrain barrier central nervous system attacking selfantigens heretofore many treatments proved can retard progression disease even though cure therefore treatments aimed improving patients quality life reducing adverse drug reactions costs essential review treatment approaches alleviate progress ms include following pharmacotherapy antibody therapy cell therapy gene therapy surgery current treatment methods ms described terms prevention myelin shedding promotion myelin regeneration protection neuronspmid33886059 doi101007 s1101002104119z,1.0
rituximab treatment refractory multiple sclerosis relapses pregnancy mult scler 2021 apr 301352458521998937 doi 101177 1352458521998937 online ahead printabstractcase summary multiple sclerosis ms disease activity declines pregnancy situations ms relapses pregnant women occur mild relapses may managed close observation severe refractory relapses may require aggressive management describe two cases rituximab used severe refractory multiple sclerosis relapses pregnancy rituximab appear complicate either pregnancy relapses either women rituximab overlooked rare refractory cases rebound relapses sometimes seen following discontinuation lymphocytesequestering diseasemodifying therapiespmid33929267 doi101177 1352458521998937,0.0
multiple sclerosis lesion segmentation brain mri using unet based wavelet pooling int j comput assist radiol surg 2021 apr 29 doi 101007 s1154802102327y online ahead printabstractpurpose purpose work segment multiple sclerosis ms lesions magnetic resonance imaging mri images lesions different sizes segmented appropriate accuracy automated segmentation powerful tool can assist professionals increase accuracy disease diagnosis level progressionmethods present deep neural network based unet architecture wavelet transformbased pooling replaces max pooling first part network wavelet transform used second part inverse addition decomposing input image reducing size wavelet transform highlights sharp changes image better describes local features transform multiresolution characteristic use provides improvement detection lesions different sizes segmentationresults results study show proposed method better dice similarity coefficient dsc value compared max pooling average pooling methodsconclusion proposed method better results segmenting ms lesions different sizes mri images max average pooling methods methods studiedpmid33928493 doi101007 s1154802102327y,0.0
realworld assessment interferon1b interferon1a adherence introduction betaconnect autoinjector retrospective cohort study drugs real world outcomes 2021 apr 29 doi 101007 s40801021002485 online ahead printabstractbackground interferon beta1b ifn1b interferon beta1a ifn1a immunomodulators require regular subcutaneous selfadministration patients multiple sclerosis ms however electronic autoinjector available ifn1a usobjective retrospective cohort study investigated adherence two subcutaneous diseasemodifying therapies ifn1b ifn1a two periods introduction betaconnect autoinjector ifn1b patients methods data evaluated marketscan database adults us ms diagnosis medical claim subcutaneous ifn1b ifn1a either october 2013september 2015 introduction betaconnect october 2016september 2018 patient populations propensityscore matched demographic clinical characteristics persistence recorded adherence evaluated medication possession ratio mpr results study included 196 ifn1b 365 ifn1a people ms pwms prebetaconnect period 126 ifn1b 223 ifn1a pwms postbetaconnect period prebetaconnect period proportion least 80 mpr higher ifn1a 90 ifn1b 83 postbetaconnect period proportion 80 mpr higher ifn1b 92 ifn1a 86 prebetaconnect period median persistence days higher ifn1a 199 ifn1b 152 postbetaconnect period persistence higher ifn1b 327 ifn1a 229 conclusions following introduction betaconnect exploratory study suggested pwms taking ifn1b adherent compared taking ifn1a higher persistence 90 reached 80 mpr threshold commonly used define good adherencepmid33928518 doi101007 s40801021002485,0.0
cytomegalovirus seropositivity associated reduced risk multiple sclerosis presymptomatic casecontrol study eur j neurol 2021 jun 9 doi 101111 ene14961 online ahead printabstractbackground epsteinbarr virus ebv human herpesvirus 6a hhv6a associated increased risk multiple sclerosis ms conversely infection cytomegalovirus cmv suggested reduce risk ms supporting data presymptomatic studies lacking sought increase understanding cmv ms aetiologymethods performed nested casecontrol study presymptomatically collected blood samples identified crosslinkage ms registries swedish biobanks serological antibody response cmv ebv hhv6a determined using beadbased multiplex assay odds ratio 95 confidence intervals ci cmv seropositivity risk factor ms calculated conditional logistic regression adjusted ebv hhv6a seropositivity potential interactions additive scale analysed calculating attributable proportion due interaction ap results serum samples 670 pairs matched cases controls included cmv seropositivity associated reduced risk ms 070 95 ci 056088 p 0003 statistical interactions additive scale observed seronegativity cmv seropositivity hhv6a ap 034 95 ci 006061 ebv antigen ebna1 amino acid 385420 age 2039 years ap 037 95 ci 009065 conclusions cmv seropositivity associated decreased risk ms protective role cmv infection ms aetiology supported interactions cmv seronegativity ebv hhv6a seropositivitypmid34107122 doi101111 ene14961,0.0
treating severe ms relapses pregnancy mult scler 2021 apr 3013524585211012206 doi 101177 13524585211012206 online ahead printno abstractpmid33929268 doi101177 13524585211012206,0.0
multiple sclerosis covid19 swedish experience acta neurol scand 2021 may 24 doi 101111 ane13453 online ahead printabstractthe covid19 pandemic brought challenges healthcare management patients multiple sclerosis ms concerns regarding vulnerability infections diseasemodifying therapies dmts complications raised recent published guidelines use dmts relation covid19 ms patients diverse countries lack evidencebased facts sweden exists particular interest anticd20 therapy possible risk factor severe covid19 due large number rituximabtreated patients offlabel country rapid responses swedish ms association smss swedish ms registry smsreg resulted national guidelines dmt use ms patients implementation covid19 module smsreg recently updated guidelines also included recommendations covid19 vaccination regard different dmts social distancing policies forced implementation telemedicine consultation replace inperson consultations part regular ms health care patientreported outcome measures proms smsreg useful respect paper reports experiences progress national ms health care covid19 pandemic addition offering overview present scientific contextpmid34028810 doi101111 ane13453,0.0
subjects detectable saccharomyces cerevisiae gut microbiota show deficits attention executive function j intern med 2021 may 29 doi 101111 joim13307 online ahead printno abstractpmid34051000 doi101111 joim13307,0.0
differential expression alternative splicing transcripts orbital adipose connective tissue thyroidassociated ophthalmopathy exp biol med maywood 2021 jun 215353702211017292 doi 101177 15353702211017292 online ahead printabstractthyroidassociated ophthalmopathy typical autoimmune disease orbital tissues alternative splicing significantly influences many diseases progression including cancer agerelated macular degeneration multiple sclerosis modulating expression transcripts however role thyroidassociated ophthalmopathy still unclear study differential expression transcripts differential alternative splicing genes orbital adipose connective tissues thyroidassociated ophthalmopathy patients detected using rna sequencing cuffdiff replicate multivariate analysis transcript splicing three thousand ninety six differential expression transcripts 2355 differential alternative splicing genes screened functional enrichment analysis indicated differential expression transcript differential alternative splicing genes associated immune modulation extracellular matrix remodeling adipogenesis expression sorbs1 sept2 col12a1 vcan gene transcripts verified qrtpcr conclusion prevalent alternative splicing involved disease development thyroidassociated ophthalmopathy attention paid mechanism alternative splicing explore potential therapeutic targets thyroidassociated ophthalmopathypmid34078122 doi101177 15353702211017292,0.0
longitudinal machine learning modeling ms patient trajectories improves predictions disability progression comput methods programs biomed 2021 may 18 208106180 doi 101016 jcmpb2021106180 online ahead printabstractbackground objectives research multiple sclerosis ms recently focused extracting knowledge realworld clinical data sources type data abundant data produced clinical trials potentially informative realworld clinical practice however comes cost less curated controlled data sets work aim predict disability progression optimally extracting information longitudinal patient data realworld setting special focus sporadic sampling problemmethods use machine learning methods suited patient trajectories modeling recurrent neural networks tensor factorization subset 6682 patients msbase registry usedresults can predict disability progression patients twoyear horizon rocauc 085 represents 32 decrease ranking pair error 1auc compared reference methods using static clinical featuresconclusions compared models available literature work uses complete patient history ms disease progression prediction represents step forward towards aiassisted precision medicine mspmid34146771 doi101016 jcmpb2021106180,0.0
genetic diseases mimicking multiple sclerosis postgrad med 2021 jun 21 doi 101080 0032548120211945898 online ahead printabstractmultiple sclerosis ms inflammatory neurodegenerative disorder manifesting gradual progressive loss neurological functions patients present relapsingremitting disease courses extensive research recent decades expounded insights presentations diagnostic features ms groups genetic diseases cadasil leukodystrophies example frequently misdiagnosed ms due overlapping clinical radiological features delayed identification diseases late adulthood can lead severe neurological complications herein discuss genetic diseases potential mimic multiple sclerosis highlights clinical identification practicing pearls may aid physicians recognizing msmimics genetic background clinical settingspmid34152933 doi101080 0032548120211945898,0.0
dimethyl fumarate improves cognitive deficits chronic cerebral hypoperfusion rats alleviating inflammation oxidative stress ferroptosis via nrf2 nfb signal pathway int immunopharmacol 2021 jun 18 98107844 doi 101016 jintimp2021107844 online ahead printabstractcerebrovascular disease risk factors cause persistent decrease cerebral blood flow chronic cerebral hypoperfusion cch major foundation vascular cognitive impairment vci hippocampus extremely vulnerable cerebral ischemia hypoxia oxidative stress neuroinflammation injury important pathophysiological mechanisms process closely related hippocampal neurons damage loss dimethyl fumarate dmf fdaapproved therapeutic multiple sclerosis ms plays protective role multiple neurological disorders studies shown dmf exerts antiinflammatory antioxidant effects via nrf2 nfb signaling pathway thus study aimed evaluate neuroprotective effect dmf cch rat model ferroptosis novel defined irondependent cell death form found strongly associated pathophysiology cch emerging evidences shown inhibition ferroptosis targeting nrf2 exerted neuroprotective effect neurodegeneration diseases also investigated whether dmf can alleviate cognitive deficits inhibition ferroptosis nrf2 signaling pathway study dmf intragastric consecutive five weeks 100 mg kg day behavior test histological molecular biochemical analysis performed found dmf treatment significantly improved cognitive deficits partially reversed hippocampus neuronal damage loss caused cch dmf treatment decreased hippocampus il1 tnf il6 proinflammatory cytokines concentration mediated nfb signaling pathway dmf also alleviated hippocampus oxidative stress reducing mda increasing gsh sod levels also closely associated ferroptosis besides dmf treatment reduced expression ptgs2 increased expression fth1 xct iron content also reduced important features related ferroptosis furthermore dmf activated nrf2 signaling pathway upregulated expression ho1 nqo1 gpx4 outcomes indicated dmf can improve cognitive impairment rats cch possibly alleviating neuroinflammation oxidative stress damage inhibiting ferroptosis hippocampal neurons overall results provide new evidence neuroprotective role dmfpmid34153667 doi101016 jintimp2021107844,1.0
translation poly gr frame c9orf72als ftd regulated ciselements involved alternative splicing neurobiol aging 2021 may 8 105327332 doi 101016 jneurobiolaging202104030 online ahead printabstractggggcc g4c2 repeat expansion first intron c9orf72 common genetic cause amyotrophic lateral sclerosis frontotemporal dementia two devastating agedependent neurodegenerative disorders sense antisense repeat rnas can translated 5 different dipeptide repeat proteins poly gr toxic various cellular animal models however remains unknown poly gr synthesized patient neurons using reporter construct containing 70 g4c2 repeats flanked human intronic exonic sequences show translation poly gr frame depend repeats cug start codon poly ga frame suggesting poly gr produced ribosomal frameshifting poly ga frame however deletion analysis suggests translation poly gr frame depends length intronic sequence 5 adjacent g4c2 repeats moreover several 5 cis elements predicted involved alternative splicing regulates poly gr synthesis results suggest translation repeat rnas poly gr frame regulated multiple cis elements likely rna secondary structures associated rna binding proteinspmid34157654 doi101016 jneurobiolaging202104030,0.0
regulation b cell functions snitrosoglutathione eae model redox biol 2021 jun 23 45102053 doi 101016 jredox2021102053 online ahead printabstractb cells play protective pathogenic roles t cellmediated autoimmune diseases releasing regulatory vs pathogenic cytokines b celldepleting therapy attempted various autoimmune diseases efficacy varies can even worsen symptoms due depletion b cells releasing regulatory cytokines along b cells releasing pathogenic cytokines report snitrosoglutathione gsno gsnoreductase gsnor inhibitor n6022 drive upregulation regulatory cytokine il10 downregulation pathogenic effector cytokine il6 b cells protected neuroinflammatory disease experimental autoimmune encephalomyelitis eae human mouse b cells gsno n6022mediated regulation il10 vs il6 limited regulatory b cells also broad range b cell subsets antibodysecreting cells adoptive transfer b cells n6022 treated eae mice eae mice deficient gsnor gene also regulated t cell balance treg th17 reduced clinical disease recipient eae mice data presented provide evidence role gsno shifting b cell immune balance il10 il6 preclinical relevance n6022 firstinclass drug targeting gsnor proven human safety therapeutics autoimmune disorders including multiple sclerosispmid34175668 doi101016 jredox2021102053,0.0
interferongamma release assay testing assess covid19 vaccination response sarscov2 seronegative patient rituximab case report int j infect dis 2021 jun 30s12019712 21 005427 doi 101016 jijid202106054 online ahead printabstractwe describe case 44yearold female rituximab treatment multiple sclerosis undetectable sarscov2 igg specific antibodies eighteen days second dose sarscov2 vaccine interferongamma release assay testing sarscov2 positive day nineteen demonstrating robust tcell mediated response despite lack antibodymediated responsepmid34216738 doi101016 jijid202106054,0.0
cellular molecular regulation programmed death1 programmed death ligand system role multiple sclerosis autoimmune diseases j autoimmun 2021 jul 23 123102702 doi 101016 jjaut2021102702 online ahead printabstractprogrammed cell death 1 pd1 receptor ligands pdls essential maintain peripheral immune tolerance avoid tissue damage consequently altered gene protein expression system coinhibitory molecules involved development cancer autoimmunity substantial progress achieved study pd1 pdls system terms regulatory mechanisms therapy however role pd1 pdls pathway neuroinflammation less explored despite potential target treatment neurodegenerative diseases multiple sclerosis ms prevalent chronic inflammatory autoimmune disease central nervous system leads demyelination axonal damage young adults recent studies highlighted key role pd1 pdls pathway inducing neuroprotective response restraining t cell activation neurodegeneration ms review outline molecular cellular mechanisms regulating gene expression protein synthesis traffic pd1 pdls well relevant processes control pd1 pdls engagement immunological synapse antigenpresenting cells t cells also highlight recent findings regarding role pd1 pdls pathway ms murine model experimental autoimmune encephalomyelitis eae including contribution pd1 expressing follicular helper t tfh cells pathogenesis diseases addition compare contrast results found ms eae evidence reported autoimmune diseases experimental models review pd1 pdlstargeting therapeutic approachespmid34311143 doi101016 jjaut2021102702,1.0
migraine multiple sclerosis chronic inflammatory diseases rev neurol paris 2021 jul 26s00353787 21 006160 doi 101016 jneurol202107005 online ahead printabstractmigraine prevalent disease worldwide major cause disability known long time migraine associated neurogenic inflammation epidemiological studies shown migraine comorbid several chronic inflammatory diseases including multiple sclerosis ms chronic inflammatory rheumatic diseases cirds inflammatory bowel diseases ibds brief narrative review highlights recent data supporting link migraine three chronic inflammatory diseases studies found migraine prevalence approximately twofold higher diseases compared general population causal link migraine chronic inflammatory diseases identified yet suggest systemic mediators cytokines gut microbiome make migraine worse add significant risks systemic inflammation biomarkers gut microbiome modification certainly avenues worth exploringpmid34325914 doi101016 jneurol202107005,0.0
intrathecal immunoglobulin m synthesis independent biomarker higher disease activity severity multiple sclerosis ann neurol 2021 may 31 doi 101002 ana26137 online ahead printabstractobjective aimed determine whether relapsing multiple sclerosis intrathecal igm igg synthesis associated outcomes reflecting inflammatory activity chronic worseningmethods compared csf analysis clinical mri data serum neurofilament light chain snfl levels baseline followup 530 patients relapsing ms patients categorized presence oligoclonal igg bands ocgb intrathecal synthesis igg igm iggintrathecal fraction igmif relations time first relapse snfl concentrations t2w lesions ms severity score msss time initiation high efficacy therapy analyzed covariate adjusted statistical modelsresults categorical analysis patients igmif median time first relapse 28 months shorter msss average higher 111 steps compared without intrathecal immunoglobulin synthesis moreover patients igmif higher snfl concentrations new enlarging t2w lesions higher total t2w lesion counts p 001 associations absent equally smaller patients positive ocgb ocgb iggif furthermore quantitative analyses revealed patients igmif median time first relapse initiation high efficacy therapy shorter 32 203 months p 001 compared patients igmif median dosedependent associations also found igmif iggif mri defined disease activity snflinterpretation large study supports value intrathecal igm synthesis independent biomarker disease activity severity relapsing ms article protected copyright rights reservedpmid34057235 doi101002 ana26137,0.0
prognostic impact total metabolic tumor volume large bcell lymphoma patients receiving car tcell therapy ann hematol 2021 jul 8 doi 101007 s00277021045606 online ahead printabstractchimeric antigen receptor car tcell therapy provides longterm remissions patients relapsed refractory r r large bcell lymphoma lbcl total metabolic tumor volume tmtv assessed 18ffluorodeoxyglucose positron emission tomography 18fdgpet confirmed prognostic value setting chemoimmunotherapy predictive role car tcell therapy fully established thirtyfive patients r r lbcl received car tcells included study tmtv maximum standardized uptake value suvmax measured baseline 1month car tcell infusion best response included 9 26 patients complete metabolic response cmr 16 46 partial metabolic response pmr median followup 76 months median pfs os 34 82 months respectively high baseline tmtv 25 cm3 associated lower pfs median pfs 23 vs 89 months hr 344 95 ci 118101 p 002 high baseline tmtv also showed trend towards shorter os hr 63 95 ci 083479 p 008 baseline suvmax significant impact efficacy endpoints tmtv suvmax values showed association adverse events metabolic tumor burden parameters measured 18fdgpet car tcell infusion can identify lbcl patients benefit therapypmid34236497 doi101007 s00277021045606,0.0
eeg power spectral dynamics associated listening adverse conditions psychophysiology 2021 jun 23e13877 doi 101111 psyp13877 online ahead printabstractadverse listening conditions increase demand cognitive resources needed speech comprehension exploratory study aimed identify independent power spectral features eeg useful studying cognitive processes involved effortful listening listeners performed coordinate response measure task singletalker masker 0db signaltonoise ratio sounds left unfiltered degraded lowpass filtering independent component analysis ica used identify independent components ics eeg data power spectral dynamics analyzed frontal midline theta left frontal right frontal left mu right mu left temporal parietal left occipital central occipital right occipital clusters ics identified ic clusters showed significant listeningrelated changes power spectrum included sustained theta enhancements gamma enhancements alpha enhancements alpha suppression beta enhancements mu rhythm suppression several effects absent negligible using traditional channel analyses comparison filtered unfiltered speech revealed stronger alpha suppression parietal central occipital clusters ics filtered speech condition replicates recent findings showing greater alpha suppression listening difficulty increases also suggests alphaband effects can stem multiple cortical sources lay advantages ica approach restrictive analyses used late study listening effort also make suggestions moving hypothesisdriven studies regarding power spectral features revealedpmid34161612 doi101111 psyp13877,0.0
evaluation corneal sensitivity multiple sclerosis patients indian j ophthalmol 2021 sep 69 9 24212424 doi 104103 ijoijo_3052_20abstractpurpose measure corneal sensitivity patients multiple sclerosis ms compare normal values study correlation different disease characteristicsmethods corneal sensitivity 28 ms patients compared corneal sensitivity 28 age gendermatched normal controls corneal sensitivity measured using cochetbonnet esthesiometer correlated duration type severity indexes diseaseresults corneal sensitivity comparable groups p 079 statistically significant correlation found corneal sensitivity duration ms p 055 severity indexes ms expanded disability status scale edss p 052 global multiple sclerosis severity score msss p 064 following subgroup analysis primary progressive ppms form ms reduced corneal sensitivity p 0023 remittentrecurrent rrms secondary progressive spms clinically isolated cis forms ms reduction corneal sensitivity roc curve analysis showed area curve 048conclusion exception ppms subtype ms patients similar corneal sensitivity comparison controls cochetbonnet esthesiometer seem good diagnostic tool disease severity marker patients mspmid34427235 doi104103 ijoijo_3052_20,0.0
aerobic reserve capacity multiple sclerosispreliminary evidence acta neurol scand 2021 apr 29 doi 101111 ane13441 online ahead printabstractobjectives aerobic reserve capacity reflects available energy performing everyday life tasks studied older adult populations preliminary study examined proof concept measurement aerobic reserve capacity multiple sclerosis ms materials methods twentyone fully ambulatory people ms performed maximal cardiopulmonary exercise test cpet calculated aerobic reserve capacity based difference peak aerobic power vo2peak first stage oxygen consumption vo2 participants completed assessments disability expanded disability status scale edss cognition symbol digit modalities test sdmt mood beck depression inventory bdi walking endurance sixminute walk distance 6mwd walking speed timed twentyfoot walk t25fw impact ms multiple sclerosis impact scale msis29 anthropometric measurements height weight results aerobic reserve capacity 93 37 ml kg min aerobic reserve capacity positively associated vo2peak 67 p 01 time exhaustion 63 p 01 sdmt 51 p 05 aerobic reserve capacity negatively associated bmi 62 p 01 rhr 047 p 05 conclusion provide preliminary evidence aerobic reserve capacity feasible outcome derived maximal cpet eg modified balke protocol ms aerobic reserve capacity associated clinically relevant outcomes become important outcome rehabilitation future researchpmid33914899 doi101111 ane13441,0.0
editorial quot mri findings arachnoiditis revisited classification neededquot j magn reson imaging 2021 mar 13 doi 101002 jmri27597 online ahead printno abstractpmid33713514 doi101002 jmri27597,0.0
telitacicept first approval drugs 2021 aug 31 doi 101007 s40265021015911 online ahead printabstracttelitacicept taiai fusion protein comprising recombinant transmembrane activator calcium modulator cyclophilin ligand interactor taci receptor fused fragment crystallizable fc domain human immunoglobulin g igg telitacicept developed yantai rongchang pharmaceutical subsidiary remegen treatment b cellmediated autoimmune diseases systemic lupus erythematosus sle rheumatoid arthritis ra multiple sclerosis ms telitacicept binds neutralizes activity two cellsignalling molecules blymphocyte stimulator blys proliferationinducing ligand april thereby suppressing development survival plasma cells mature b cells march 2021 telitacicept received first approval china treatment patients active sle clinical studies telitacicept several indications including iga nephropathy ms myasthenia gravis neuromyelitis optica spectrum disorders ra sjgrens syndrome underway china article summarizes milestones development telitacicept leading first approval slepmid34463932 doi101007 s40265021015911,0.0
role meningeal populations type ii innate lymphoid cells modulating neuroinflammation neurodegenerative diseases exp mol med 2021 sep 6 doi 101038 s12276021006605 online ahead printabstractrecent research meningeal lymphatics revealed neverbefore appreciated role type ii innate lymphoid cells ilc2s modulating neuroinflammation central nervous system cns date role ilc2mediated inflammation periphery well studied however exact distribution ilc2s cns therefore putative role modulating neuroinflammation neurodegenerative diseases alzheimers disease ad multiple sclerosis ms parkinsons disease pd major depressive disorder mdd remain highly elusive review current evidence ilc2mediated modulation neuroinflammatory cues ie il33 il25 il5 il13 il10 tnf cxcl16cxcr6 within cns highlight distribution ilc2s periphery cns discuss challenges associated cell typespecific targeting important therapeutics comprehensive understanding roles ilc2s mediating responding inflammatory cues may provide valuable insight potential therapeutic strategies many dementiarelated disorderspmid34489558 doi101038 s12276021006605,0.0
hladrb11501 coreceptor epsteinbarr virus linking genetic environmental risk factors multiple sclerosis eur j immunol 2021 may 21 doi 101002 eji202149179 online ahead printno abstractpmid34019695 doi101002 eji202149179,0.0
classification visualization longitudinal patterns medication dose application interferonbeta1a amitriptyline patients multiple sclerosis pharmacoepidemiol drug saf 2021 may 25 doi 101002 pds5297 online ahead printabstractpurpose describing patterns use including changes dose interruptions challenging groupbased trajectory modelling gbtm can used identify individuals similar dose patterns provide intuitive graphical representation dose patterns groups identified using gbtm illustrate approach using two drugs different combinations available dosagesmethods drew data patients ms followed 1977 2014 montral using two subcohorts subjects subcohort patients taking interferonbeta1a another patients taking amitriptyline identified initial cohort use gbtm identify groups patients homogeneous dose patterns two drugs compared graphical representation obtained fitted values gbtm proposed approach consisted using step functions whose values corresponded mode differences characteristics across groups identified using chisquares analysis variance weighted posterior probability group membershipresults seven patterns dose identified interferonbeta1a five amitriptyline graphical representations patterns dose gbtm included values outside prescribed doses capture changes dose clearly proposed representation using step functionsconclusion proposed approach based mode visit pattern provides intuitive realistic representation dose patterns groups identified gbtmpmid34031946 doi101002 pds5297,0.0
impact previous diseasemodifying treatment effectiveness safety outcomes among patients multiple sclerosis treated alemtuzumab j neurol neurosurg psychiatry 2021 mar 12jnnp2020325304 doi 101136 jnnp2020325304 online ahead printabstractobjectives alemtuzumab effective patients active multiple sclerosis complex safety profile including development secondary autoimmunity patients enrolled randomised clinical trials alemtuzumab either treatment nave pretreated injectable substances previous diseasemodifying treatments dmts used study cohorts therefore associated risks might yet remain unidentifiedmethods retrospectively evaluated prospective dualcentre alemtuzumab cohort 170 patients examined baseline characteristics well safety effectiveness outcomes including time first relapse time 3 months confirmed disability worsening time secondary autoimmunityresults regression analysis showed among previously used dmts pretreatment fingolimod n33 hrs time first relapse hr 5420 95 ci 2520 11660 p0001 time worsening disability hr 7676 95 ci 2870 20534 p0001 additionally patients pretreated fingolimod likely experience spinal relapses 55 vs 10 among previously nave patients p0001 increased risk secondary autoimmunity hr 5875 95 ci 2126 1627 p0001 conclusion realworld setting demonstrated suboptimal disease control increased risk secondary autoimmunity following alemtuzumab among patients previously treated fingolimod data can provide guidance improving ms therapeutic managementpmid33712515 doi101136 jnnp2020325304,1.0
effect ponesimod exposure total lymphocyte dynamics patients multiple sclerosis clin pharmacokinet 2021 apr 29 doi 101007 s40262021010199 online ahead printabstractobjective aim study characterize relationship ponesimod plasma concentrations temporal evolution lymphocyte counts multiple sclerosis ms patientsmethods population pharmacokinetic pk pk pharmacodynamic pd models developed using data phase ii iii trials impact clinically relevant covariates pk pd parameters assessed simulations conducted evaluate maximal lymphocyte count reduction ponesimod treatment time required total lymphocyte counts return normal values treatment interruptionresults ms patients ponesimod pk characterized low mean apparent plasma clearance 552 l h moderate mean apparent volume distribution steady state 239 l model developed indicated none evaluated covariates age sex formulation food body weight clinical condition renal impairment clinically relevant impact pk pd parameters ms patients total lymphocyte counts characterized maximum reduction 880 half maximal inhibitory concentration ic50 549 ng ml simulations indicated patients normal hepatic function treated ponesimod 20 mg daily total lymphocyte counts reduced 41 baseline trough stopping treatment lymphocyte counts restored normal levels within one weekconclusions population pk pd model wellcharacterized pk ponesimod time course total lymphocyte counts ms patients additionally none evaluated covariates clinically relevant impact taken consideration assessing risk infection administration liveattenuated vaccines concomitant use immunosuppressantspmid33914285 doi101007 s40262021010199,0.0
matched neurofeedback fmri differentially activates rewardrelated circuits active sham groups j neuroimaging 2021 jun 8 doi 101111 jon12899 online ahead printabstractbackground purpose functional mri neurofeedback fmrinf leverages brains ability selfregulate activity however selfregulation processes engaged fmrinf incompletely understood used matched feedback fmrinf experimental protocol investigate whether brain processes recognize true neurofeedback signalsmethods implemented existing fmrinf protocol train lateralized motor activity using fingertap task conjunction realtime feedback twelve healthy righthanded adult participants assigned age sexmatched active sham study groups matched participant pairs received visual feedback based brain activity participant active group compared groupaveraged activation maps neurofeedback analyzed changes lateralized motor activity due neurofeedbackresults active sham groups demonstrated different brain activation feedback neurofeedback particular higher activation visual cortex secondary somatosensory cortex right inferior frontal gyrus active group compared sham group conversely sham participants demonstrated higher activation anterior cingulate cortex left frontal pole posterior superior temporal gyrus despite differing brain activations neurofeedback neither group demonstrated significant improvement lateralized motor activity pre postfeedback scan session also observed significant difference pre postfeedback activation maps suggesting significant fingertap related functional reorganization occurredconclusions findings suggest fmri neurofeedback paradigms monitor incorporate activity regions reported provide enhanced efficacy research investigation clinical interventionpmid34101274 doi101111 jon12899,0.0
cognitive recovery people relapsing remitting multiple sclerosis randomized clinical trial virtual realitybased neurorehabilitation clin neurol neurosurg 2021 jul 21 208106828 doi 101016 jclineuro2021106828 online ahead printabstractbackground multiple sclerosis ms can adversely affect several domains cognitive function including attention information processing memory learning executive functions visuospatial skills recent years technological innovations proven effective improving motor cognitive impairment neurological patients including affected msobjective study aims evaluate cognitive outcomes rehabilitation training virtual reality rehabilitation system vrrs patients suffering msmethods patients randomized either control group cg 15 patients receiving conventional cognitive rehab experimental group eg using virtual reality vr 15 patients groups underwent amount cognitive training 3 times week 8 weeks submitted neuropsychological assessment t0 rehabilitation treatment t1 results data showed conventional vr cognitive rehabilitation approaches improved mood p 0001 visuospatial skills however eg significant improvement specific cognitive domains p 0001 including learning ability shortterm verbal memory lexical access ability well quality life related mental states foundconclusions present study demonstrated vr can motivational effective tool cognitive recovery ms patientspmid34332269 doi101016 jclineuro2021106828,0.0
clinical significance antiro52 trim21 antibodies adult patients connective tissue diseases eur j intern med 2021 may 7s09536205 21 001436 doi 101016 jejim202104020 online ahead printabstractobjectives clinical significance antiro52 antibodies connective tissue diseases ctd controversial antiro52 antibodies might associated severe ctd phenotype especially interstitial lung disease ild aims study evaluate ild prevalence severity prevalence micro macroangiopathy ctdassociated cancers ctd antiro52 antibodiesmethods ctd patients antiro52 antibody screening immunoblot diagnosis enrolled two groups retrospectively formed according presence antiro52 antibodies unbiased 11 matching ctd types unsupervised multiple correspondence analysis hierarchical clustering analysis used aggregate antiro52 positive patients subgroupsresults 408 ctd patients included antiro52 antibodies detected 33 ctd patients antiro52 antibodies associated ild ctd diagnosis 478 vs 230 33 95 ic 14 80 p 0008 even adjusting presence antiro60 antibodies especially patients antisynthetase syndrome primary sjgren syndrome systemic sclerosis micro macroangiopathy frequent antiro52 positive ctd patients 186 vs 97 p 002 ctd patients antiro52 antibodies experienced frequent relapses required immunosuppressive drugs clusters 4 5 identified antiro52 positive ctd patients severe ild clinical features systemic sclerosis antisynthetase syndrome respectivelyconclusions found antiro52 antibodies independently associated ild ctd patients irrespective ctd type antiro52 antibodies associated severity relapsing disease course ctd patientspmid33972152 doi101016 jejim202104020,0.0
thrombin receptor modulates astroglianeuron trophic coupling neural repair spinal cord injury glia 2021 apr 22 doi 101002 glia24012 online ahead printabstractexcessive activation thrombin receptor protease activated receptor 1 par1 implicated diverse neuropathologies neurodegenerative conditions neurotrauma par1 knockout mice show improved outcomes experimental spinal cord injury sci however information regarding underpinning cellular molecular mechanisms lacking demonstrate genetic blockade par1 female mice results improvements sensorimotor coordination thoracic spinal cord lateral compression injury document improved neuron preservation increases synapsin1 presynaptic proteins gap43 growth cone marker 30 days recovery period improvements coupled signs enhanced myelin resiliency repair including increases number mature oligodendrocytes progenitors abundance myelin basic protein significant increases substrates neural recovery accompanied reduced astrocyte serp1 microglial monocyte cd68 inos proinflammatory markers coordinate increases astrocyte s100a10 emp1 microglial arg1 markers reflective prorepair activities complementary astrocyteneuron coculture bioassays suggest astrocytes par1 lossoffunction promote neuron survival neurite outgrowth additionally proneurite outgrowth effects switching astrocyte par1 blocked inhibiting trkb high affinity receptor brain derived neurotrophic factor altogether studies demonstrate unique modulatory roles par1 regulating glialneuron interactions including capacity neurotrophic factor signaling underscore position neurobiological intersections critical response cns injury capacity regenerative repair restoration functionpmid33887067 doi101002 glia24012,1.0
methanolic extract sambucus ebulus ameliorates clinical symptoms experimental type 1 diabetes antiinflammatory immunomodulatory actions cell j 2021 sep 23 4 465473 doi 1022074 cellj20217287 epub 2021 aug 29abstractobjective sambucus ebulus se famous traditional iranian medicine grown north iran traditional medicine antiinflammatory effects se utilized inflammatory joint diseases insect bites infectious wounds edema eczema type1 diabetes autoimmune disease characterized destruction pancreatic beta cells immune system first time investigated effect methanolic extract se cd4+ cd8+ regulatory t cells experimental type 1 diabetes t1d materials methods experimental study fiftysix c57bl6 mice 8 groups g1g8 enrolled diabetes induced multiple lowdose streptozotocin mlds protocol mice daily treated se extract 200 400 mg kg doses 35 days fasting blood glucose weekly measured glucometer islets insulin content analyzed immunohistochemistry percentage cd4+ cd8+ regulatory t cells cytokines production levels evaluated flow cytometer elisa respectivelyresults clinical symptoms diabetes significantly alleviated g2 group mice received 400 mg kg se extract immunohistochemistry analysis showed insulin content islets increased g2 group mice immunophenotyping analysis indicated percentage cd4+ cd8+ t cells g2 group mice significantly decreased se extract significantly increased percentage regulatory t cells extract g2 g4 groups mice significantly decreased ifn il17levels extract significantly increased il10 g2 group miceconclusion protective effect se extract mldsinduced diabetes partly due decrease cd4+ cd8+ t cells increase treg cells resulting inflammation reduction pancreatic isletspmid34455723 doi1022074 cellj20217287,0.0
exposureresponse analysis clinical efficacy ponesimod randomized phase ii study patients multiple sclerosis clin pharmacokinet 2021 apr 29 doi 101007 s40262021010202 online ahead printabstractbackground objective ponesimod sphingosphine1phosphate receptor modulator developed treatment multiple sclerosis effects diseasemodifying treatments magnetic resonance imaging mri lesions relapsing multiple sclerosis accurately predict effects clinical relapses therefore mri lesion counts generally accepted efficacy endpoints phase ii clinical studies multiple sclerosis diseasemodifying treatments characterize effect ponesimod systemic exposure cumulative number t1 gadoliniumenhancing gd+ lesions annualized relapse rate phase iib studymethods study assessed cumulative number new gd+ lesions t1weighted mri scans primary endpoint weeks 12 16 20 24 annualized relapse rate secondary endpoint effect demographic prognostic covariates sex age weight t1 gd+ lesions baseline expanded disability status scale score baseline explored analyses performed using nonmem version 730 icon plc results increase ponesimod exposure led statistically significant decrease cumulative t1 gd+ lesions mri week 12 24 treatment increasing ponesimod daily dose beyond 20 mg provide significant additional benefits sex age t1 gd+ lesions baseline expanded disability status scale score baseline associated higher number new cumulative t1 gd+ week 12 24 treatmentconclusions analysis shows relationship ponesimod exposure cumulative number new t1 gd+ lesions sex age t1 gd+ lesions baseline expanded disability status score baseline found importantly associated magnitude ponesimod effect consequently indication analyses dosage adjustments based explored covariates warrantedclinical trial registration clinicaltrialsgov identifier nct01006265 registration date 1 november 2009pmid33914286 doi101007 s40262021010202,0.0
journeys patients trigeminal neuralgia background multiple sclerosis pain manag 2021 jun 9 doi 102217 pmt20210001 online ahead printabstractaim multiple sclerosis ms well recognized secondary cause trigeminal neuralgia tn case series detail management patients tn ms pwtnms presenting specialist unit materials methods prospective patient database used extract key clinical data pharmacological psychometric surgical management 20 pwtnms results 65 pwtnms underwent surgical interventions management pain12 20 achieved remission periods surgery medication significant improvement noted global impression change illustrated p 0001 conclusion pwtnms require multifaceted approach combining polypharmacy surgical interventions psychological support developing selfmanagement skills crucial patients live well painpmid34105358 doi102217 pmt20210001,0.0
expression levels il17 il23 cytokinetargeting micrornas 20 21 26 155 let7 patients relapsingremitting multiple sclerosis neurol res 2021 jun 1616 doi 101080 0161641220211935099 online ahead printabstractobjective although multiple sclerosis ms known immunemediated disease little known etiopathogenesis micrornas mirnas small noncoding proteins involved regulation gene expression tcell activation potential neurodegenerative diseases research topic interest recent years cytokines play important role course pathogenesis ms aim present study analyze expression levels mir20 mir21 mir26 mir155 let7 target cytokines interleukin il17 il23 order evaluate relationship ms mirnas modulate expression cytokines involved autoimmune pathwaymaterials methods study included 20 relapsingremitting multiple sclerosis ms patients least 18 years age undergoing outpatient immunomodulatory therapy 20 healthy unrelated individuals systemic disease taking medication control group peripheral blood samples collected participants edtacontaining tubes plasma isolated cdna synthesis cdna samples mirna expression levels quantitatively analyzed via melting curve analysis using miscript sybr green kit realtime pcr device results comparison mirna expression levels peripheral blood samples ms patients healthy subjects revealed ms patients significant upregulation mir20 downregulation mir26 mir155 compared control group p0005 conclusion dysregulation mirna expression may play role pathogenesis mspmid34130607 doi101080 0161641220211935099,0.0
emerging covid19 neurological manifestations present outlook potential neurological challenges covid19 pandemic mol neurobiol 2021 jun 24 doi 101007 s12035021024506 online ahead printabstractthe unremitting coronavirus disease 2019 covid19 pandemic caused novel severe acute respiratory syndrome coronavirus 2 sarscov2 marked yearlong phase public health adversaries severely compromised healthcare globally early evidence covid19 noted impact pulmonary cardiovascular functions multiple studies recent time shed light substantial neurological complications though comprehensive understanding cause s mechanism s neuropathological outcomes scarce present review conferred evidence neurological complications covid19 patients shed light sarscov2 infection routes including hematogenous direct neuronal lymphatic tissue cerebrospinal fluid infiltration infected immune cells underlying mechanism sarscov2 invasion central nervous system cns also discussed uptodate manner reviewed impact covid19 developing diverse neurologic manifestations associated cns peripheral nervous system pns skeletal muscle also preexisting neurological diseases including alzheimers disease parkinsons disease multiple sclerosis epilepsy myasthenia gravis furthermore discussed involvement key factors including age sex comorbidity disease severity exacerbating neurologic manifestations covid19 patients outlook present therapeutic strategies state existing challenges covid19 management also accessed conclusively present report provides comprehensive review covid19related neurological complications emphasizes need early clinical management ongoing covid19 pandemicpmid34169443 doi101007 s12035021024506,0.0
notch1 signaling enhances collagen expression fibrosis mouse uterus biofactors 2021 jul 28 doi 101002 biof1771 online ahead printabstractfibrosis pathological process characterized abnormal activation fibroblasts increased synthesis extracellular matrix components including collagens may lead loss proper tissue architecture organ function clinical diseases systemic sclerosis liver fibrosis excess accumulation collagens considered primary indicator fibrosis notch signaling reported involved fibrosis many different organs including liver previous study showed uterinespecific overactivation canonical notch1 signaling mouse uterus pgrcre + rosa26n1icd + oex results complete infertility consequence multiple developmental physiological defects together increased collagen accumulation evidenced massons staining study detected expressions 44 collagen genes notch1 gainoffunction transgenic mice found 18 collagens largely affected another aspect using intrauterine adhesion model iua mimicked fibrosis mouse uterine results suggested notch receptors upregulated 3 days induction fibrilforming collagen began upregulate 6 days surgery furthermore induced iua n1icdoex mice expression collagens fibrosis levels significantly enhanced last notch signaling inhibitor secretase inhibitor n n 3 5difl uorophenacetyl lalanyl sphenylglycine tbutyl ester dapt pretreatment alleviate expression collagens symptoms fibrosis results demonstrate notch signaling may play role upregulating collagens expression endometrial fibrosis might potential target fibrosis therapy endometriumpmid34320265 doi101002 biof1771,0.0
lateonset ms associated increased rate reaching disability milestones j neurol 2021 mar 7 doi 101007 s00415021104900 online ahead printabstractobjective describe patient characteristics assess risk disability worsening patients different age groups focus lateonset multiple sclerosis loms defined disease onset age 50 yearsmethods nationwide populationbased danish multiple sclerosis registry served data source described baseline characteristics analyzed rates reaching expanded disability status scale edss milestonesresults identified 28 232 patients ms known year clinical onset 2661 loms loms group higher proportion males patients primary progressive disease course less likely receive diseasemodifying therapy initial rate reaching edss milestone 6 diagnosis higher loms hazard ratio hr 153 95 confidence interval ci 114206 however assessing risk reaching edss 6 according age hr significantly lower loms group hr 0307 95 ci 02210426 conclusion clinical characteristics treatment approaches patients loms differ younger counterparts following diagnosis patients loms initially increased rate reaching edss score 6 however risk reaching edss score 6 given age higher patients nonlomspmid33677675 doi101007 s00415021104900,0.0
tumefactive demyelination appearing multiple cystic brain lesions world neurosurg 2021 jun 12s18788750 21 008457 doi 101016 jwneu202105132 online ahead printabstracttumefactive demyelinating lesions tdl rare sequalae idiopathic inflammatory demyelinating diseases iidd central nervous system cns propensity mimic tumor abscess poses diagnostic challenge clinician case depicts tdl causing right hand focal sensory seizures otherwise healthy 35yearold female differential diagnosis metastatic disease infection excluded histology ensuing magnetic resonance imaging mri cord addition cerebral spinal fluid csf analysis supported diagnosis iidd case highlights need consider rare diagnosis tdl imaging shows cystic brain lesions otherwise healthy young adultpmid34129977 doi101016 jwneu202105132,1.0
evaluation effects metformin adenosine monophosphateactivated protein kinase activator spatial learning memory rat model multiple sclerosis disease biomed pharmacother 2021 jul 22 141111932 doi 101016 jbiopha2021111932 online ahead printabstractin patients multiple sclerosis ms disease cognitive deficits detected destruction hippocampus cognitive impairment one common signs ms recent studies showed metformin met wideranging effects treatment diseases tried study preservative effects met adenosine monophosphateactivated protein kinase ampk activator hippocampus dentate gyrus dg neuronal firing pattern motor coordination learning memory loss following ms induction ms induction done local ethidium bromide eb injection rat hippocampus rats treated met 200 mg kg two weeks spatial memory learning status assessed using morris water maze neuronal singleunit recording measured hippocampus dg decapitation bilateral hippocampi separated measure malondialdehyde mda treatment met ameliorated latency times path lengths p 005 p 001 p 0001 1th 2th 3th 4th days met + ms group respectively percent total time spent goal quarter average number spikes bin decreased significantly ms rats compared sham group p 0001 significantly increased metformintreated ms group met + ms p 001 p 0001 met treatment rats ms significantly reduced concentration mda indicator lipid peroxidation compared untreated groups observations show increase neuronal activity sensorymotor coordination improvement spatial memory ms rats treated met appears via increment ampkpmid34323699 doi101016 jbiopha2021111932,1.0
sequencing escalation paradigms ms therapies time rethink j neurol neurosurg psychiatry 2021 jun 8jnnp2020325811 doi 101136 jnnp2020325811 online ahead printno abstractpmid34103341 doi101136 jnnp2020325811,0.0
effect exoskeletonassisted rehabilitation prefrontal cortex multiple sclerosis patients neuroimaging pilot study brain topogr 2021 jun 28 doi 101007 s1054802100858w online ahead printabstractapplication passive fully articulated exoskeleton called human body posturizer hbp demonstrated improve mobility response accuracy ambulation multiple sclerosis ms patients using functional magnetic imaging fmri visuomotor discrimination task performed pilot study evaluate effect hbp neural correlates motor cognitive functions typically impaired ms patients specifically tested effect 6week multidisciplinary rehabilitation intervention two groups ms patients control group followed standard physiotherapeutic rehabilitation protocol experimental group used hbp physical exercises addition standard protocol found treatment experimental group exhibited significant lower activity compared control group inferior frontal gyrus posttreatment activity reduction can explained retour normal range amount ifg activity observed experimental patients similar observed healthy subjects findings indicate use hbp rehabilitation intervention normalizes prefrontal activity mitigating cortical hyperactivity associated mspmid34181126 doi101007 s1054802100858w,0.0
integrative study genetic variants brain tissue expression identifies viral etiology potential drug targets multiple sclerosis mol cell neurosci 2021 jul 17103656 doi 101016 jmcn2021103656 online ahead printabstractmultiple sclerosis ms neuroinflammatory disorder leading chronic disability brain lesions ms commonly arise normalappearing white matter nawm genomewide association studies gwas identified genetic variants associated ms transcriptome alterations observed casecontrol studies nawm developed crossdataset evaluation cde function networkbased tool edgeweighted dense module search gwas ew_dmgwas applied cde integrate publicly available ms gwas summary statistics 41 505 cases controls collectively 38 nawm expression samples using human protein interactome reference network investigate biological underpinnings ms etiology validated resulting modules colocalization gwas expression quantitative trait loci eqtl signals using gtex consortium expression data msrelevant tissues 14 brain tissues 4 immunerelated tissues network assessments included drug target query functional gene set enrichment analysis cde prioritized ms nawm network containing 55 unique genes gene list enriched pvalue 234 107 gwaseqtl colocalized genes cdk4 ifitm3 mapk1 mapk3 mettl12b pik3r2 resultant network also included drug signatures fdaapproved medications gene set enrichment analysis revealed top functional term intracellular transport virus among viral pathways prioritize critical genes resultant network cdk4 ifitm3 mapk1 mapk3 mettl12b pik3r2 enriched drug signatures suggest potential drug targets drug repositioning strategies ms finally propose mechanisms potential ms viral onset based prioritized gene set functional enrichment analysispmid34284104 doi101016 jmcn2021103656,0.0
creating realworld data united states healthcare claimsbased adaptation kurtzke functional systems scores assessing multiple sclerosis severity progression adv ther 2021 jul 31 doi 101007 s12325021018589 online ahead printabstractintroduction article describes development unique mapping kurtzke functional systems scores kfss international classification diseases 9th revision clinical modification icd9cm codes among multiple sclerosis ms patients within us integrated delivery network idn valid identification increasing disability may allow deeper insight ms progression possible treatmentsmethods cohort study identified ms patients idn intermountain healthcare experienced clinicians informaticists mapped electronic health record icd9cm codes kfss components generating modified kurtzke expanded disability status scale edss modified edss scores used assess disability progression calculating means medians ranges changes kfss modified edss scoresresults overall 608 2960 205 patients identified ms progression presented wide range scores edss 10point scale median range first second edss scores 0 06 5 18 respectively median range change first second score 5 175 median first kfss score systems 0 mean differed among components highest mean first kfss score 106 measured sensory function lowest 012 cerebellar functions 544 patients first edss scores 25 group 752 151 second edss scores group 355 6 respectively 62 patients first edss score 355 group 581 second edss scores group 6conclusion innovative mapping technique promising method future comparative effectiveness safety research diseasemodifying therapy realworld data repositories future research validate expand method another healthcare database encouragedpmid34333756 doi101007 s12325021018589,0.0
antifibrotics systemic sclerosis best pract res clin rheumatol 2021 apr 7101671 doi 101016 jberh2021101671 online ahead printabstractsystemic sclerosis ssc rare complex disease involving multiple organs high morbidity mortality fibrosis hallmark ssc although vascular inflammatory mechanisms also implicated pathogenesis disease management challenging due heterogeneous presentation limited number controlled clinical trials guide treating clinicians immunosuppressive agents used prevent progression especially lung irreversible injury occurs although modest benefit nintedanib tyrosine kinase inhibitor recently demonstrated safety efficacy interstitial lung disease ild associated ssc many antifibrotics assessed possible beneficial therapies promising results important unmet need remains clarify patients agent therapy initiated achieve optimal outcomes review summarizes available evidence current emerging antifibrotic therapies ssc patientspmid33839046 doi101016 jberh2021101671,0.0
rehabilitative treatment case aphasia onset multiple sclerosis neurol sci 2021 jun 14 doi 101007 s10072021053642 online ahead printno abstractpmid34125324 doi101007 s10072021053642,0.0
covid19 multiple sclerosis patients treated dimethyl fumarate j neurol 2021 feb 20 doi 101007 s00415021104464 online ahead printno abstractpmid33611610 doi101007 s00415021104464,0.0
excess weight central adiposity proinflammatory diet consumption patients neuromyelitis optica spectrum disorder mult scler relat disord 2021 jun 24 54103110 doi 101016 jmsard2021103110 online ahead printabstractpurpose characterize nutritional status consumed dietary inflammatory index dii individuals neuromyelitis optica spectrum disorder nmosd methods anthropometric clinical data expanded disability status scale edss anthropometric data body mass index bmi waist circumference wc waisttohip ratio whr percentage fat mass fm data food consumption 24hour recall collected determine dietary inflammatory index dii according shivappa et al statistical analysis descriptive measures statistical tests used significance level set p 005results higher prevalence females 868 abdominal fat accumulation individuals demonstrated 579 730 703 300 according bmi wc whr andfm respectively correlation edss score nutritional status positive correlation administered corticosteroid dose bmi r 055 p 0002 wc r 055 p 0003 whr r 041 p 0033 mean dii 499 109 indicating consumption proinflammatory diet difference dii according gender p 001 casecontrol segment significant difference dii groups 251 95 ci 173 327 higher risk developing disease dii 441 3025 95 ci 670 13647 conclusions diets high inflammatory potential associated increased risk nmosdpmid34214879 doi101016 jmsard2021103110,0.0
transglutaminase 2 therapeutic target neurological conditions expert opin ther targets 2021 oct 5 doi 101080 1472822220211989410 online ahead printabstractintroduction transglutaminase 2 tg2 implicated numerous neurological conditions including neurodegenerative diseases multiple sclerosis cns injury early studies role tg2 neurodegenerative conditions focused ability crosslink proteins insoluble aggregates however recent studies suggested unlikely primary mechanism tg2 contributes pathogenic processes although specific mechanisms tg2 involved neurological conditions clearly defined tg2 regulates numerous cellular processes contribute specific disease given fact tg2 stressinduced gene elevated disease injury conditions tg2 inhibitors may useful neurotherapeuticsareas covered overview tg2 different tg2 inhibitors brief review tg2 neurodegenerative diseases multiple sclerosis cns injury inhibitors tested different models database search https pubmedncbinlmnihgov prior july 1 2021expert opinion currently appears unlikely inhibiting tg2 context neurodegenerative diseases therapeutically advantageous however multiple sclerosis cns injuries tg2 inhibitors may potential therapeutically useful thus rationale developmentpmid34607527 doi101080 1472822220211989410,0.0
microbiome systemic sclerosis review current evidence best pract res clin rheumatol 2021 apr 10101687 doi 101016 jberh2021101687 online ahead printabstractsystemic sclerosis ssc characterized immune dysregulation vasculopathy fibrosis multiple organs gastrointestinal gi tract common internal organ manifestation contributes significant morbidity mortality patients ssc emerging reports identified unique microbial taxa alterations gi microbiome patients ssc compared healthy controls hc taxa alterations include differences phyla eg bacteroidetes genera eg bacteroides clostridium faecalibacterium lactobacillus level addition genera associated severe gi symptoms eg prevotella akkermansia review summarizes current evidence factors influencing gi microbiome gi microbiome alterations ssc compared hc ssc subgroups according disease manifestations current exploration therapeutic interventions target gi microbiome discussedpmid33849778 doi101016 jberh2021101687,0.0
assessing brain injury topographically using mr neurite orientation dispersion density imaging multiple sclerosis j neuroimaging 2021 may 25 doi 101111 jon12876 online ahead printabstractbackground purpose axonal injury key player disability persons multiple sclerosis pwms yet detecting measuring vivo challenging neurite orientation dispersion density imaging noddi proposes novel framework probing axonal integrity vivo noddi 30 tesla used quantify tissue damage pwms relationship disease progressionmethods eighteen pwms 4 clinically isolated syndrome 11 relapsing remitting 3 secondary progressive ms nine age sexmatched healthy controls underwent brain mri inclusive clinical sequences multishell diffusion acquisition parametric maps axial diffusivity ad neurite density index ndi apparent isotropic volume fraction ivf orientation dispersion index odi fitted anatomically matched regions interest used quantify ad noddiderived metrics assess relations measures disease progressionresults ad ndi ivf odi significantly differed chronic black holes cbhs t2lesions latter normal appearing white matter nawm metrics except ivf significantly differed nawm located next cbh situated contralaterally nawm odi significantly associated t2lesion volume timed 25foot walk test disease durationconclusions noddi sensitive tissue injury relationship clinical progression remains limitedpmid34033187 doi101111 jon12876,0.0
patient neurologist preferences uk relapsingremitting multiple sclerosis rrms treatments findings discrete choice experiment curr med res opin 2021 jun 151 doi 101080 0300799520211940911 online ahead printabstractto evaluate compare patient neurologist preferences relapsingremitting multiple sclerosis rrms treatments respect benefits risks associated common novel diseasemodifying therapies including brain volume loss bvl methods patients nonhighly active rrms neurologists united kingdom completed online crosssectional survey patients completed one discrete choice experiment dce exercise providers completed two one focusing treatment nonhighly active rrms another focused highly active rrms respondents chose two treatment profiles varied 7 attributes identified qualitative research 2year disability progression 1year relapse rate rate bvl risks gastrointestinal symptoms flulike symptoms infection lifethreatening event bayesian modelling used estimate attributelevel weighted preferences results patients n 144 prioritized slowing rate bvl followed reducing risk infection rate 2year disability progression 1year relapse rate nonhighly active patients neurologists n 101 prioritized slowing rate bvl followed reducing 2year disability progression risk infection 1year relapse rate highly active patients neurologists prioritized lowering 1year relapse rate followed slowing rate bvl 2year disability progression 3 dces rate bvl approximately twice important reducing risks flulike symptoms gastrointestinal symptoms lifethreatening event conclusions study highlights similarities treatment preferences nonhighly active rrms among patients neurologists differences neurologists preferences treating nonhighly active vs highly active rrms research identifies bvl treatment outcome discussed physicians engage shared decisionmaking patientspmid34129418 doi101080 0300799520211940911,0.0
longterm trajectory acquired demyelinating syndrome multiple sclerosis children dev med child neurol 2021 may 3 doi 101111 dmcn14912 online ahead printabstractaim assessed frequency characteristics future trajectory monophasic acquired demyelinating syndromes ads associated conversion paediatric multiple sclerosismethod retrospective observational study sardinian children 18y age onset ads 2001 2018results identified 44 children ads 21 males 23 females median age onset 16y range 4mo18y 21 already presenting criteria paediatric multiple sclerosis mean crude prevalence ads sardinian children 592 per 100 000 incidence 31 per 100 000 per year 13 children aged 10y 119 aged 1017y mean sd followup 8 years 5 months 5y 4mo common n32 trajectory conversion paediatric multiple sclerosis onset total prevalence mean annual incidence paediatric multiple sclerosis 356 per 100 000 23 per 100 000 respectively 05 individuals aged 10y 100 older group interpretation sardinia high risk area ads children nearly half population can already diagnosed paediatric multiple sclerosis onset overall 72 ads will paediatric multiple sclerosis mean 8 yearspmid33938575 doi101111 dmcn14912,1.0
pinocembrin promotes opc differentiation remyelination via mtor signaling pathway neurosci bull 2021 jun 6 doi 101007 s12264021006967 online ahead printabstractthe exacerbation progressive multiple sclerosis ms closely associated obstruction differentiation oligodendrocyte progenitor cells opcs discover novel therapeutic compounds enhancing remyelination endogenous opcs screened myelin basic protein expression using cultured rat opcs library smallmolecule compounds one effective drugs pinocembrin remarkably promoted opc differentiation maturation without affecting cell proliferation survival based vitro effects assessed therapeutic effects pinocembrin animal models demyelinating diseases demonstrated pinocembrin significantly ameliorated progression experimental autoimmune encephalomyelitis eae enhanced repair demyelination lysolectininduced lesions studies indicated pinocembrin increased phosphorylation level mammalian target rapamycin mtor taken together results demonstrated pinocembrin promotes opc differentiation remyelination phosphorylated mtor pathway suggest novel therapeutic prospect natural flavonoid product treating demyelinating diseasespmid34091810 doi101007 s12264021006967,1.0
protective effect mechanism nicotinamide adenine dinucleotide optic neuritis mice experimental autoimmune encephalomyelitis int immunopharmacol 2021 jun 23 98107846 doi 101016 jintimp2021107846 online ahead printabstractpatients multiple sclerosis ms commonly accompanied optic neuritis causes retinal ganglion cell rgc death even vision loss nicotinamide adenine dinucleotide nad+ can protect cell apoptosis attenuate mstriggered symptoms however effect nad+ mstriggered remains unclear herein experimental autoimmune encephalomyelitis eae established immunizing female c57bl 6 mice mog3555 peptide investigate effect nad+ prevention treatment eae mice received 250 mg kg nad+ daily via intraperitoneal injection immunization eae onset respectively ex527 10 mg kg sirt1 inhibitor intraperitoneally injected every two days explore role sirt1 nad+induced therapeutic effect eae nad+ intervention attenuated severity eae mice nad+ intervention relieved inflammatory infiltration cd3+ cd4+ cell infiltration decreased number activation microglia astrocytes optic nerve nad+ intervention also attenuated demyelination axonal loss oligodendrocyte apoptosis oligodendrocyte progenitor cell recruitment proliferation optic nerve protected rgc apoptosis retina nad+ intervention decreased proinflammatory cytokine mrna proapoptotic protein expression enhanced antiinflammatory cytokine mrna expression sirt1 signaling optic nerve retina regulated th1 th17 tregs immune response spleen addition ex527 reversed therapeutic effect nad+ eae suggesting nad+ prevented mstriggered activating sirt1 signaling pathway study shows potential nad+ used drug preventing treating msrelated onpmid34174704 doi101016 jintimp2021107846,1.0
multiple sclerosis impact dental care br dent j 2021 sep 231 5 281286 doi 101038 s4141502133330 epub 2021 sep 10abstractmultiple sclerosis affects approximately 130 000 people uk due wide variation symptoms associated condition variable severity provision dental care affected patients must determined individuals specific needs will often vary significantly time paper reviews aetiology presentation current management multiple sclerosis explores impact oral health provision dental carepmid34508197 doi101038 s4141502133330,0.0
fantastic iga plasma cells find immunol rev 2021 may 27 doi 101111 imr12980 online ahead printabstractiga produced large quantities mucosal surfaces iga+ plasma cells pc protecting host pathogens restricting commensal access subepithelium becoming increasingly appreciated iga+ pc constrained mucosal barrier sites rather iga+ pc may leave sites provide host defense immunoregulatory function review will outline iga+ pc generated within mucosae subsequently migrate classical effector site gut lamina propria provide examples iga+ pc displacement gut parts body referencing examples homeostasis inflammation lastly will speculate mechanisms iga+ pc displacement tissues aim provide new perspective iga+ pc truly fantastic beasts immune system identify new places find thempmid34046908 doi101111 imr12980,0.0
post covid19 transverse myelitis case report review literature ann med surg lond 2021 sep 69102749 doi 101016 jamsu2021102749 epub 2021 aug 23abstractintroduction coronavirus disease 2019 covid19 emerged severe acute respiratory syndrome coronavirus 2 sarscov2 recently various complications reported aim current study report rare case transverse myelitis recovering covid19case report 34yearold lady presented inability walk one day duration due lower limb weakness two weeks recovery covid19 developed progressive intermittent leg pain paresthesia weakness sides brain cervical mri showed evidence short segment inflammatory enhancing lesion upper cervical region c1 level patient treated conservativelydiscussion transverse myelitis many different causes occurs autoimmune phenomenon postinfection vaccination may result direct infection acquired demyelinating disease like multiple sclerosisconclusion although sporadic finding sarscov2 can cause transverse myelitis condition responds medical therapypmid34457267 pmcpmc8380545 doi101016 jamsu2021102749,1.0
missing n1 jittered p2 electrophysiological correlates patternglare time frequency domain eur j neurosci 2021 aug 9 doi 101111 ejn15419 online ahead printabstractexcessive sensitivity certain visual stimuli cortical hyperexcitability associated number neurological disorders including migraine epilepsy multiple sclerosis autism possibly dyslexia others show disruptive sensitivity visual stimuli obvious pathology symptom profile visual stress can extend discomfort nausea used event related potentials eprs explore neural correlates visual stress headache proneness analysed erps response thick 037 c deg medium 3 c deg thin 12 c deg gratings using mass univariate analysis considering three factors general population headache proneness visual stress discomfort found relationships erp features headache discomfort factors stimulus main effects driven medium stimulus regardless participant characteristics participants high discomfort ratings larger p1 components initial presentation medium stimuli suggesting initial cortical hyperexcitability later suppressed participants high headache ratings showed atypical n1p2 components medium stripes relative stimuli effect present repeated stimulus presentation effects also explored frequency domain suggesting variations intertrial theta band phase coherence results suggest discomfort headache response striped stimuli related different neural processes however exploration needed determine whether results translate clinical migraine populationpmid34374142 doi101111 ejn15419,0.0
onychomycosis patients multiple sclerosis prevalence clinical description mycological dermoscopic study mexican population int j dermatol 2021 apr 15 doi 101111 ijd15580 online ahead printabstractbackground multiple sclerosis ms chronic demyelinating disease related hladr8 susceptibility onychomycosis found mexican mestizos hladr8 frequency onychomycosis neurological disease unknownobjectives determine frequency onychomycosis clinical mycological dermoscopic characteristics patients ms comparison general populationmethods observational crosssectional casecontrol study patients ms october 2017 february 2018 age gender ms type time progression diagnosis date baseline treatment collected signed informed consent neurological exploration clinical examination fingernails toenails onychomycosis conducted mycological dermoscopic studies infected nails performed patients clinical diagnosis onychomycosis healthy control group taken case 11 paired age genderresults frequency onychomycosis patients ms higher healthy population 32 vs 26 p 0509 higher frequency nondermatophyte fungi found although statistically significant clinical manifestations dermoscopic findings patients ms onychomycosis similar general populationconclusion frequency onychomycosis patients ms slightly higher general population possible association hladr8 susceptibility factor onychomycosis proposed etiology opportunistic fungi ms patients onychomycosis may related immunosuppressive treatmentpmid33855705 doi101111 ijd15580,1.0
ms covid19 challenge asymptomatic covid19 infection treatment cladribine neurol sci 2021 jun 24 doi 101007 s10072021054096 online ahead printabstractbackground use diseasemodifying therapies dmts people multiple sclerosis pwms may affect covid19 infection outcomes due dmts immunomodulatory immunosuppressive effects immune response yet unknown issues early response infection well postinfection development immunity virus treatments due interaction immune systemmethods report two asymptomatic cases covid19 patients relapsingremitting multiple sclerosis rrms shortly starting cladribine therapy developed antisarscov2 antibody responseresults patients ms newly initiated treatment cladribine tablets may experience asymptomatic covid19 infection may develop immunity sarscov2conclusion observations raise probability dmts immunosuppressive effects cladribine may considered treatment option selected ms patients high disease activity covid19 pandemicpmid34165650 doi101007 s10072021054096,0.0
whole brain adiabatic t 1rho relaxation along fictitious field imaging healthy volunteers patients multiple sclerosis initial findings j magn reson imaging 2021 mar 6 doi 101002 jmri27586 online ahead printabstractbackground preclinical models multiple sclerosis ms adiabatic t1rho t1adiab relaxation along fictitious field raff imaging demonstrated potential noninvasively characterize mspurpose evaluate feasibility whole brain t1adiab raff imaging healthy volunteers patients msstudy type single institutional clinical trialsubjects 38 healthy volunteers 2469 years 21 patients 2659 years ms five healthy volunteers underwent second mr examination performed within 8 days clinical disease severity expanded disability status scale edss multiple sclerosis severity score msss evaluated baseline 1year followup fu field strength sequence raff second rotating frame reference raff2 performed 3 t using 3dfastfield echo magnetization preparation rf amplitude 1174 t corresponding value t1adiab 1350 t t1 t2 flairweighted images acquired reconstruction voxel size 10 10 10 mm3 assessment parametric maps t1adiab raff2 traff2 calculated using monoexponential model semiautomatic segmentation ms lesions white matter wm gray matter gm wm tracks performed using t1 t2 flairweighted imagesstatistical tests regression analysis used evaluated correlation t1adiab traff2 age disease severity friedman test followed wilcoxon signed rank test differences tissue types shortterm repeatability evaluated voxel levelresults t1adiab traff2 demonstrated good shortterm repeatability relative differences voxel level range 61119 differences t1adiab traff2 tissue types ms patients significant p 005 t1adiab traff2 correlated p 0001 baseline edss mssm disease progression fu p 0001 data conclusion whole brain t1adiab traff2 3 t feasible significant differences t1adiab traff2 values tissues time correlation disease severityevidence level 1 technical efficacy stage 1pmid33675564 doi101002 jmri27586,0.0
evaluation cognitive impairment patients multiple sclerosis using georgian language montreal cognitive assessment georgian med news 2021 sep 318 128132abstractthe main objective study evaluate prevalence risk factors cognitive impairment patients multiple sclerosis fiftythree patients multiple sclerosis enrolled crosssectional study study participants underwent neurological status examination cognitive screening montreal cognitive assessment beck depression inventory used assess mental health statistical analysis performed using spss software version 260 overall prevalence cognitive impairment group 42 found higher physical disability progressive disease course main riskfactors cognitive decline patients multiple sclerosispmid34628393,0.0
temporally independent association multiple evanescent white dot syndrome optic neuritis graefes arch clin exp ophthalmol 2021 may 29 doi 101007 s00417021052492 online ahead printabstractpurpose describe three patients developed temporally distinct episodes optic neuritis multiple evanescent white dot syndrome mewds methods retrospectively reviewed medical records imaging studies three women evaluated tertiary referral center optic neuritis mewdsresults three otherwise healthy women aged 17 36 41 developed temporally separated episodes optic neuritis mewds time periods two events 3 48 60 months two three cases optic neuritis event preceded episode mewds patient endorsed prodromal flulike symptoms prior developing vision loss mean presenting visual acuities better optic neuritis episode logmar 0360 snellen 20 46 retinal event logmar 0684 snellen 20 97 three patients improvement vision mean visual acuity 20 29 logmar 0165 last followup one patient later developed idiopathic noninfectious posterior uveitis another developed multiple sclerosis requiring treatmentconclusion rare association patients can develop optic neuritis mewds within eye different time points unknown whether patients even higher risk developing systemic autoimmune disease patients either mewds optic neuritis alonepmid34050810 doi101007 s00417021052492,0.0
immunosenescence multiple sclerosis identification new therapeutic targets autoimmun rev 2021 jul 5102893 doi 101016 jautrev2021102893 online ahead printabstractthe number elderly multiple sclerosis ms patients growing mainly due increase life expectancy general population availability effective diseasemodifying treatments however current treatments reduce frequency relapses slow progression disease stop disability accumulation associated disease progression one possible explanation impact immunosenescence associated accumulation unusual immune cell subsets thought role development early ageing process autoimmunity provide recent overview senescence affects immune cell function involved pathogenesis autoimmune diseases particularly ms numerous studies demonstrated agerelated immune changes experimental autoimmune encephalomyelitis models premature onset immunosenescence demonstrated ms patients therefore potential therapeutic strategies based rejuvenating immune system proposed senolytics regenerative strategies using haematopoietic stem cells therapies based rejuvenating oligodendrocyte precursor cells microglia monocytes thymus cells senescent b t cells capable reversing process immunosenescence beneficial impact progression mspmid34237417 doi101016 jautrev2021102893,1.0
novel cellbased analysis reveals regiondependent changes microglial dynamics grey matter cuprizone model demyelination neurobiol dis 2021 jul 15105449 doi 101016 jnbd2021105449 online ahead printabstractmicroglia key players multiple sclerosis ms expressing many susceptibility genes disease constantly survey brain microenvironment precise functional relationships microglia pathological processes remain unknown performed detailed assessment microglial dynamics three distinct grey matter regions cuprizoneinduced demyelination model found microglial activation preceded detectable demyelination showed regional specificities prominent phagocytic activity cortical layer 5 early hypertrophic morphology hippocampal ca1 demyelination happened earliest cortical layer 5 although complete ca1 cortical layer 2 3 microglial activation demyelination less pronounced microglia became hyperramified slower process movement remyelination thereby maintaining local brain surveillance profiling microglia using specific morphological motility parameters revealed regionspecific heterogeneity microglial responses grey matter might serve sensitive indicators progression cns demyelinating diseasespmid34274460 doi101016 jnbd2021105449,1.0
brain activity contingent neuropsychological function fmri study verbal working memory amyotrophic lateral sclerosis eur j neurol 2021 jun 3 doi 101111 ene14957 online ahead printabstractintroduction amyotrophic lateral sclerosis als devastating neurodegenerative disease causes progressive degeneration neurons motor nonmotor brain regions affecting multiple cognitive domains memory performed functional magnetic resonance imaging fmri study explore working memory function alsmethods contribute growing research field employs structural functional neuroimaging investigate effect als different working memory components explored localization intensity alterations neural activity using fmri first study specifically address verbal working memory via fmri context als employed verbal nback task 0back 2back conditionsresults despite als patients showing unimpaired accuracies p 0724 reaction times p 00785 significantly increased brain activity frontotemporal parietal regions 2back minus 0back contrast patients compared controls using nonparametric statistics 5000 permutations tthreshold 25 discussion increased brain activity frontotemporal parietal regions working memory performance largely associated better neuropsychological function within als group suggesting compensatory effect working memory execution study therefore adds current knowledge neural correlates working memory als contributes nuanced understanding hyperactivity cognitive processes fmri studies alspmid34081813 doi101111 ene14957,0.0
multiple sclerosis doubling mhc trends genet 2021 may 15s01689525 21 001086 doi 101016 jtig202104012 online ahead printabstracthuman leukocyte antigen hla encoded surface molecules present antigenic peptides t lymphocytes play key role adaptive immune responses besides physiological role defending host infectious pathogens specific alleles serve genetic risk factors autoimmune diseases multiple sclerosis ms autoimmune disease affects brain spinal cord association hladr15 haplotype described early 1970s short opinion piece discusses difficulties disentangling details association recent observations functional involvement one also second gene hladr15 haplotype information important understanding pathomechanism ms also antigenspecific therapiespmid34006391 doi101016 jtig202104012,0.0
clinicalmathematical analysis interrelations character prognosis peculiarities onsets different types multiple sclerosis course georgian med news 2021 sep 318 132138abstractaim study assess prognostic value indicators characterizing course multiple sclerosis onset ms using clinicalmathematical analysis patients ms different prognosis good uncertain relapsingremitting type uncertain poor progressive types clinical course neurological examination using expanded disability status scale edss questionnaire method determination yules coefficient association coefficient colligation separating hyperplane method correlation analysis indicators onset high correlation prognostic value defined means yules coefficient rank onset indicators separating hyperplane method diagnostic weight determined different variants prognosis types ms correlation relations onset indices type ms calculated presented graphical form correlation analysis connections indicators built according single algorithm combines alternative programs patterns severe mild onset can subsequently compete final outcome disease results clinicalmathematical analysis onsets different types ms high reliability indicate diagnostic informativity mentioned investigation methods prognosis ms disease typepmid34628394,0.0
assessment commonly used methods determine myelinreactivity t cells multiple sclerosis clin immunol 2021 aug 2108817 doi 101016 jclim2021108817 online ahead printabstractmany studies analyzed myelinreactivity t cells multiple sclerosis ms however conflicting results study compare methods determine myelin reactivity t cells aim delineate cause inconsistency literature challenging t cells myelin antigens found significant increase antigenreactivity t cells patients ms using elispotassay contrast cfsedilution assay comparing two assays showed myelinreactive t cells detected elispotassay originated primarily effector memory t cells contrast myelinreactive t cells cfseassay representing population nave central memory effector memory t cells diversity t cell populations activated two assays likely contribute discrepancy found literature encourages thorough considerations choosing assay determine antigenspecificity t cells future studiespmid34352391 doi101016 jclim2021108817,1.0
longterm cognitive deficits traumatic brain injury associated microglia activation clin immunol 2021 jul 30108815 doi 101016 jclim2021108815 online ahead printabstracttraumatic brain injury tbi prevalent head injuries microglia play essential role homeostasis diseases central nervous system hypothesize microglia may play beneficial detrimental role tbi depending state activation duration study evaluated whether tbi results spatiotemporal change microglia phenotype whether affects sensorymotor learning memory functions male c57bl 6 mice used panel neurological behavioral tests multicolor flow cytometrybased data analysis followed unsupervised clustering evaluate isolated microglia injured brain tissue characterized several microglial phenotypes association cognitive deficits tbi results spatiotemporal increase activated microglia correlated negatively spatial learning memory 35 days postinjury observations define therapeutic windows accelerate translational research improve patient outcomespmid34339843 doi101016 jclim2021108815,0.0
motor higherorder functions topography human dentate nuclei identified tractography clustering methods hum brain mapp 2021 jun 4 doi 101002 hbm25551 online ahead printabstractdeep gray matter nuclei synaptic relays responsible route signals specific brain areas dentate nuclei dns represent main output channel cerebellum yet often unexplored especially humans developed multimodal mri approach identify dns topography basis connectivity well microstructural features based results defined dn parcellations deputed motor higherorder functions humans vivo wholebrain probabilistic tractography performed 25 healthy subjects human connectome project infer dn parcellations based connectivity either cerebral cerebellar cortex turn third dn atlas created inputting microstructural diffusionderived metrics unsupervised fuzzy cmeans classification algorithm analyses performed native space probability atlas maps generated standard space cerebellar lobulespecific connectivity identified one motor parcellation accounting 30 dn volume two nonmotor parcellations one cognitive one sensory occupied remaining volume two approaches provided overlapping results terms geometrical distribution identified cerebellar lobulespecific connectivity although differences volumes gender effect observed respect motor areas higherorder function representations first study indicates half dn volumes involved nonmotor functions connectivitybased microstructurebased atlases provide complementary information results represent stepahead interpretation pathological conditions involving cerebrocerebellar circuitspmid34087040 doi101002 hbm25551,0.0
pipeline quantify spinal cord atrophy deep learning application differentiation ms nmosd patients phys med 2021 aug 2 895162 doi 101016 jejmp202107030 online ahead printabstractpurpose quantitative measurement various anatomical regions brain spinal cord sc mri images used unique biomarkers consider progress effects demyelinating diseases central nervous system paper presents fullyautomated image processing pipeline quantifies sc volume mri imagesmethods proposed pipeline conducting preprocessing tasks deep convolutional network utilized segment spinal cord crosssectional area sccsa slice full segmentation certain extra slices interpolate two adjacent slices using shapebased interpolation method 3d model sc reconstructed counting voxels sc volume calculated performance proposed method sccsa segmentation evaluated 140 mri images subsequently demonstrate application proposed pipeline study differentiations sc atrophy 38 multiple sclerosis ms 25 neuromyelitis optica spectrum disorder nmosd patientsresults experimental results sccsa segmentation indicate proposed method adapted mask rcnn presented satisfactory result average dice coefficient 096 method statistical metrics including sensitivity specificity accuracy precision 9751 9998 9992 9804 respectively moreover ttest result pvalue 000089 verified significant difference sc atrophy ms nmosd patientsconclusion pipeline efficiently quantifies sc volume mri images can utilized affordable computeraided tool diagnostic purposespmid34352676 doi101016 jejmp202107030,1.0
atlas classifiersa machine learning paradigm brain mri segmentation med biol eng comput 2021 jul 27 doi 101007 s1151702102414x online ahead printabstractwe present atlas classifiers aoc conceptually novel framework brain mri segmentation aoc spatial map voxelwise multinomial logistic regression lr functions learned labeled data upon convergence resulting fixed lr weights voxel represent training dataset can therefore considered lightweight learning machine despite low capacity underfit problem aoc construction independent actual intensities test images providing flexibility train available labeled data use segmentation images different datasets modalities sense overfit training data well proposed method applied numerous publicly available datasets segmentation brain mri tissues shown robust noise outreach commonly used methods promising results also obtained multimodal crossmodality mri segmentation finally show aoc trained brain mris healthy subjects can exploited lesion segmentation multiple sclerosis patientspmid34313921 doi101007 s1151702102414x,0.0
effects reflexology pain fatigue quality life multiple sclerosis patients clinical study altern ther health med 2021 mar 31at6133 online ahead printabstractcontext multiple sclerosis ms occupies first row among diseases leads loss neurological ability without depending trauma adults reflexology one complementary therapies based activating bodys power recover special hand techniques applied feet hands positive changes spasticity pain fatigue depression cortisol levels anxiety blood pressure levels observed ms patients reflexologyobjectives study conducted determine effect reflexology pain fatigue quality life ms patientsdesign study conducted experimentally taking pretest repeated measurements reflexology control groups determined simple randomizationsetting study took place neurology clinics two university hospitals turkeyparticipants potential participants 685 patients clinics diagnosed ms 6 months least prior study group 66 patients included study 33 intervention group 33 control groupintervention reflexology applied patient intervention group 3 sessions week 12 weeks weekly pain fatigue monthly quality life evaluated intervention made control group groups received routine treatmentoutcome measures measurements occurred baseline weekly monthly throughout trial postintervention pain fatigue evaluated weekly using visual analogue scale vas fatigue severity scale fss respectively quality life evaluated monthly using multiple sclerosis quality life54 msqol54 scaleresults intervention group significant decreases observed pain scores seventh week fatigue scores fifth week p 001 assessment quality life combined physical health combined mental health scores found higher intervention group control group p 001 conclusion study indicates reflexology can used complementary alternative therapy reduce pain fatigue enhance quality life ms patientspmid33789252,0.0
supervised exercises versus telerehabilitation benefits persons multiple sclerosis acta neurol scand 2021 may 7 doi 101111 ane13448 online ahead printabstractobjectives purpose study investigate effectiveness structured telerehabilitation fatigue health status quality life qol activities daily living adl compare possible effects structured supervised exercise programs patients multiple sclerosismaterials methods study randomized singleblind trial thirty patients relapsingremitting multiple sclerosis included study randomly divided two groups structured supervised exercise group group 1 telerehabilitation group group 2 group 1 n 15 completed 12 week structured supervised exercise program group 2 n 15 completed 12 week structured homebased exercise program patients evaluated functional independence measure fim first section nottingham health profile nhpi fatigue severity scale fss quality life scale qols interventionresults significant differences found parameters groups treatment p 05 significant difference found groups regarding fimtotal fimmotor fimcognitive nhp subparameters qols p 05 betweengroup differences revealed significant difference fss nhp total favor group 1 p 05 conclusion structured homebased exercise program can alternative supervised exercises side effects patients multiple sclerosis homebased rehabilitation exercises checked controlled telerehabilitation can help patients improve healthrelated qol adl however supervised exercises can beneficial regarding fatigue health profile compared homebased exercisespmid33961295 doi101111 ane13448,0.0
antinmethyldaspartate receptor encephalitis patient multiple sclerosis dimethyl fumarate case report neurol sci 2021 jun 22 doi 101007 s1007202105385x online ahead printno abstractpmid34155564 doi101007 s1007202105385x,0.0
potential repurposing adamantane antivirals covid19 drugs r d 2021 jun 21 doi 101007 s40268021003516 online ahead printabstractseveral adamantanes established actions coronaviruses amantadine rimantadine bananins structurally related memantine effective human respiratory coronavirus hcovoc43 bovine coronavirus severe acute respiratory syndrome coronavirus 1 sarscov1 spiroadamantane amine effective coronavirus strain 229e molecular docking studies suggest amantadine may block viral e protein channel leading impaired viral propagation additionally amantadine analogues may inhibit entry virus host cell increasing ph endosomes thus inhibiting action host cell proteases cathepsin l highthroughput drug screen gene expression analysis identified compounds able downregulate cathepsin l expression fifth potent agent 466 candidates amantadine amantadine inhibits severe acute respiratory syndrome coronavirus 2 replication vitro inhibit binding spike protein ace2 adamantanes also may act coronaviruses including severe acute respiratory syndrome coronavirus 2 sarscov2 via antagonism glutamate nmda 7 subtype nicotinic acetylcholine receptor located bronchial alveolar epithelial cells nmda receptor antagonist memantine potential inhibit entry sarscov2 cell populations amantadine memantine widely employed treatment neurodegenerative diseases pathophysiologic link antiviral antiparkinson actions amantadine entertained case reports involving 23 patients reverse transcription polymerase chain reactionconfirmed coronavirus disease 2019 covid19 range comorbidities including type 2 diabetes mellitus parkinsons disease multiple sclerosis severe cognitive impairment reveal significant potential benefits amantadine memantine prevention treatment coronavirus disease 2019 neurological complicationspmid34152583 doi101007 s40268021003516,0.0
separation susceptibility sources quantitative susceptibility mapping theory phantom validation vivo application multiple sclerosis lesions different age j magn reson 2021 jul 13 330107033 doi 101016 jjmr2021107033 online ahead printabstractpurpose biological tissue phase contrast determined multiple substances iron myelin calcifications often substances occur colocated within measurement volume however quantitative susceptibility mapping can solely measure average susceptibility per voxel provide new insight disease progression mechanisms neurological diseases multiple processes demyelination iron accumulation occur simultaneously location separation susceptibility sources desirable disentangle underlying susceptibility proportionsmethods basic concept separating susceptibility effects sources different sign within one voxel include information relaxation rate r2 quantitative susceptibility mapping reconstruction pipeline presented reconstruction algorithm implemented constrained minimization problem solved using conjugate gradients algorithm evaluated using software phantom validated mri measurements phantom containing mixtures microscopic positive negative susceptibility sources data three multiple sclerosis patients used show vivo feasibilityresults numerical simulations feasibility disentangling susceptibility sources within voxel confirmed provided critera static dephasing regime fulfilled phantom experiments magnitude decay kernel essential reconstruction parameter algorithm determined dm1945t1s1ppm1 susceptibility sources separated mri measurement dataconclusions conclusion study detailed description implementation algorithm separation positive negative susceptibility sources within volume element well limitations presented validated quantitatively simulation phantom experiments first time application multiple sclerosis lesions shows promising results vivo usabilitypmid34303117 doi101016 jjmr2021107033,1.0
neurological manifestations sarscov2 infection hospitalised children adolescents uk prospective national cohort study lancet child adolesc health 2021 jul 14s23524642 21 001930 doi 101016 s23524642 21 001930 online ahead printabstractbackground spectrum neurological psychiatric complications associated paediatric sarscov2 infection poorly understood aimed analyse range prevalence complications hospitalised children adolescentsmethods prospective national cohort study uk using online network secure rapidresponse notification portals established coronerve study group paediatric neurologists invited notify children adolescents age 18 years admitted hospital neurological psychiatric disorders considered sarscov2 infection relevant presentation patients excluded neurological consultation neurological investigations meet definition confirmed sarscov2 infection positive pcr respiratory spinal fluid samples serology antisarscov2 igg royal college paediatrics child health criteria paediatric inflammatory multisystem syndrome temporally associated sarscov2 pimsts individuals classified either primary neurological disorder associated covid19 covid19 neurology group pimsts neurological features pimsts neurology group denominator hospitalised children adolescents covid19 collated national health service england datafindings april 2 2020 feb 1 2021 52 cases identified england 51 cases among 1334 children adolescents hospitalised covid19 giving estimated prevalence 38 95 ci 2950 cases per 100 paediatric patients 22 42 patients female 30 58 male median age 9 years range 117 36 69 patients black asian 16 31 white 27 52 52 patients classified covid19 neurology group 25 48 classified pimsts neurology group covid19 neurology group diagnoses included status epilepticus n7 encephalitis n5 guillainbarr syndrome n5 acute demyelinating syndrome n3 chorea n2 psychosis n2 isolated encephalopathy n2 transient ischaemic attack n1 pimsts neurology group often multiple features included encephalopathy n22 88 peripheral nervous system involvement n10 40 behavioural change n9 36 hallucinations presentation n6 24 recognised neuroimmune disorders common covid19 neurology group pimsts neurology group 13 48 27 patients vs 1 1 25 patients p00003 compared covid19 neurology group patients pimsts neurology group admitted intensive care 20 80 25 patients vs six 22 27 patients p00001 received immunomodulatory treatment 22 88 patients vs 12 44 patients p0045 17 33 patients 10 37 covid19 neurology group 7 28 pimsts neurology group discharged disability one 2 died stroke pimsts neurology group interpretation study identified key differences primary neurological disorder versus pimsts compared patients primary neurological disorder patients pimsts needed intensive care outcomes similar overall studies investigate underlying mechanisms neurological involvement covid19 longerterm outcomesfunding uk research innovation medical research council wellcome trust national institute health researchpmid34273304 doi101016 s23524642 21 001930,1.0
covid19related autoimmune disorders central nervous system cradc new entity autoimmun rev 2021 jul 3102888 doi 101016 jautrev2021102888 online ahead printno abstractpmid34229045 doi101016 jautrev2021102888,0.0
beneficial metabolic effects trem2 obesity uncoupled expression macrophages diabetes 2021 feb 24db200572 doi 102337 db200572 online ahead printabstractobesityinduced white adipose tissue wat hypertrophy associated elevated adipose tissue macrophage atm content overexpression triggering receptor expressed myeloid cells 2 trem2 reportedly increases adiposity worsening health paradoxically using insulin resistance elevated fat mass hypercholesterolemia hallmarks unhealthy obesity recent report demonstrated atmexpressed trem2 promoted health identified mice trem2 deficiency aggravated dietinduced insulin resistance hepatic steatosis independently fat cholesterol levels metabolomics linked trem2 deficiency elevated obesityinstigated serum ceramides correlated impaired insulin sensitivity remarkably inhibiting ceramide synthesis exerted influences trem2dependent atm remodeling inflammation lipid load restored insulin tolerance reversing adipose hypertrophy secondary hepatic steatosis trem2deficient animals bone marrow transplantation experiments revealed unremarkable influences immune cellexpressed trem2 health instead demonstrating watintrinsic mechanisms impinging sphingolipid metabolism dominate trem2s systemic protective effects metabolic healthpmid33627323 doi102337 db200572,0.0
temporal overexpression il22 reg3 differentially impacts severity experimental autoimmune encephalomyelitis immunology 2021 apr 20 doi 101111 imm13340 online ahead printabstractil22 alphahelical cytokine belongs il10 family cytokines il22 produced rort+ innate adaptive lymphocytes including ilc3 t inkt th17 th22 cells granulocytes il22 receptor expressed primarily nonhematopoietic cells il22 critical barrier immunity mucosal surfaces steadystate infection although il22 knockout mice previously shown develop experimental autoimmune encephalomyelitis eae murine model multiple sclerosis ms temporal il22 manipulation adult mice affect eae course studied previously study overexpressed il22 via hydrodynamic gene delivery blocked via neutralizing antibodies c57bl 6 mice explore therapeutic impact il22 modulation eae course il22 overexpression significantly decreased eae scores demyelination reduced infiltration ifn+il17a+ th17 cells central nervous system cns neutralization il22 alter eae pathology significantly show il22 mediated protection independent reg3 epithelial cellderived antimicrobial peptide induced il22 thus overexpression reg3 significantly exacerbated eae scores demyelination infiltration ifn+il17a+ il17a+gmcsf+ th17 cells cns also show reg3 may inhibit il2mediated stat5 signaling impair expansion treg cells vivo vitro finally reg3 overexpression dramatically impacted intestinal microbiota eae results provide novel insight role il22 il22induced antimicrobial peptide reg3 pathogenesis cns inflammation murine model mspmid33876425 doi101111 imm13340,1.0
pathologysupported genetic testing method disability prevention multiple sclerosis ms part targeting metabolic model rather autoimmunity metab brain dis 2021 apr 28 doi 101007 s1101102100711w online ahead printabstractin review part investigate scientific evidence multiple sclerosis ms caused death oligodendrocytes cells synthesize myelin due lack biochemical nutritional factors involved mitochondrial energy production cells ms damage myelin sheaths surrounding nerve axons causes disruption signal transmission brain peripheral organs may lead disability however extent disability deterred use ms medication based autoimmune hypothesis ms rather disability associated loss brain volume related loss grey white matter pathologysupported genetic testing psgt method developed personalized assessment treatment prevent brain volume loss disability progression ms discussed involves identification msrelated pathogenic pathways underpinned genetic variation lifestyle risk factors may converge biochemical abnormalities associated adverse expanded disability status scale edss outcomes magnetic resonance imaging mri findings patient followup metabolic model presented hypothesizes disability may prevented reversed oligodendrocytes protected nutritional reserve evidence validity metabolic model may evaluated consecutive test cases following psgt method part ii review two cases presented describe psgt procedures clinical outcomes individuals diagnosed mspmid33909200 doi101007 s1101102100711w,1.0
oral health experiences limited scleroderma patient j dent hyg 2021 aug 95 4 5969abstractpurpose limited scleroderma associated significant risks orofacial complex purpose mixed methods study investigate experiences participants limited scleroderma related oral health quality life oral healthmethods sequential mixed methods study used population individuals diagnosed limited scleroderma participants recruited rheumatology specialists referral social media purposive sampling used recruit participants interviewed validated oral health impact profile ohip mouth handicap systemic sclerosis mhiss instruments semistructured interviews used data collection quantitative data analyzed using descriptive statistics qualitative data reported thematic analysisresults fortyeight n48 qualifying participants participated quantitative phase 12 n12 participated qualitative phase based likert scale 04 mean ohip14 scores ranged 276 285 anxiety oral condition embarrassed oral problems oral selfconsciousness greatest negative impact quality life mean mhiss scores ranged 213 311 highest ohrqol scores related dry mouth symptoms factors influencing oral healthrelated quality life varied dry mouth microstomia prevalent complaints thematic analysis revealed challenges oral health included selfcare professional dental care factors depended upon individual disease expression financial emotional burdens also influenced participants oral healthconclusion oral healthrelated quality life limited scleroderma impacted multiple factors oral health care professionals must seek improved treatment modalities address needs vulnerable individuals future studies related interprofessional collaborative care scleroderma specialists recommendedpmid34376545,0.0
type o blood group associates higher antijc polyomavirus antibody levels brain behav 2021 jul 21 doi 101002 brb32298 online ahead printabstractbackground patients multiple sclerosis ms high antijc polyomavirus jcpyv antibodies blood increased risk development progressive multifocal leukoencephalopathy pml treated ms test hypothesis type o blood group associates antijcpyv antibody levels risk developing pml characterized abo blood group antigen blood samples 62 patients pml 64 ms controls without pmlmethods monocentric retrospective cohort study antijcpyv antibody levels arbitrary units au determined sera using elisabased method blood group specific antibodies using standardised test erythrocytesresults antijcpyv antibody levels higher individuals blood group o compared blood groups o median au 129 o median au 53 p 005 association observed closely related bk virus 62 patients pml 29 47 95 confidence interval ci 3559 blood group o showed nonsignificant trend differ expected distribution german population 41 ms controls studied 36 95 ci 2548 conclusion abo blood group o antigen associates higher antijcpyv antibody levels may impact risk later development pml overrepresentation blood group o cases pml line previous publication larger studies warranted assess potential value host genetic markers abo status pml risk prediction immunotherapypmid34291599 doi101002 brb32298,1.0
correction pathologysupported genetic testing method disability prevention multiple sclerosis ms part ii insights two ms cases metab brain dis 2021 apr 28 doi 101007 s11011021007227 online ahead printno abstractpmid33909201 doi101007 s11011021007227,0.0
quot kicking screamingquot quot gracefully concedingquot creative nonfiction stories aging multiple sclerosis qual health res 2021 apr 3010497323211009864 doi 101177 10497323211009864 online ahead printabstractaging multiple sclerosis ms complex phenomenon individuals report physical cognitive dysfunctions regarding combined experiences whereas others report perceived improvements quality life beyond little known regarding people make sense come embody negative positive experiences ms thus objectives explore people made sense aging ms b present artful engaging transformative way achieve conducted 40 semistructured interviews older adults ms analyzed data using pluralistic narrative analyses presented results two creative nonfictions detail process creating nonfictions presenting different stories aging ms namely kicking screaming gracefully conceding offer recommendations implications using stories knowledge translation devices critique limitations stories practicepmid33926326 doi101177 10497323211009864,0.0
closing part d coverage gap outofpocket costs multiple sclerosis drugs neurol clin pract 2021 aug 11 4 298303 doi 101212 cpj0000000000000929abstractobjective determine whether closing part d coverage gap donut hole 2010 2019 lowered patients outofpocket costs diseasemodifying therapies dmts multiple sclerosis ms methods using nationwide medicare formulary drug pricing files analyzed part d drug benefit design dmt prices 2010 2016 2019 calculated average monthly list prices dmts available year 4 dmts 2010 11 dmts 2016 14 dmts 2019 projected patients annual outofpocket cost dmt alone standard part d plan year estimated potential savings attributable closing coverage gap 2010 2019 beneficiaries cost sharing dropped 100 25 3 scenarios increase price inflationindexed price increase 3 annually observed price increaseresults median monthly dmt prices rose 2 804 5 987 7 009 years 2010 2016 2019 respectively median projected annual outofpocket costs rose 5 916 6 229 6 618 unchanged inflationindexed dmt price changes closing coverage gap reduced annual outofpocket costs 2 260 38 reduction 1 744 29 reduction respectively despite lowest monthly price generic glatiramer acetate among highest outofpocket costs 6 731 6 939 year 2019conclusions medicare part d beneficiaries can pay thousands dollars yearly pocket dmts closing part d coverage gap reduce outofpocket costs patients simultaneous increases dmt pricespmid34484929 pmcpmc8382442 doi101212 cpj0000000000000929,0.0
association symbol digit modalities test regional cortex thickness young adults relapsingremitting multiple sclerosis clin neurol neurosurg 2021 jul 10 207106805 doi 101016 jclineuro2021106805 online ahead printabstractbackground multiple sclerosis ms demyelinating disease central nervous system predominating within young adults cognitive disorders common ms associated several magnetic resonance imaging mri markers especially brain atrophy many found symbol digit modalities test sdmt sensitive individual cognitive measure relevant ms however relationship sdmt regional brain cortex thickness young adults relapsingremitting multiple sclerosis yarrms little explored purpose study investigate association sdmt regional cortex thickness yarrms freesurfer automatic brain structure segmentation methodmethod twentyeight yarrms patients 1835 years old enrolled present study informed consent information including gender age disease duration number relapses annual relapse rate collected patients clinical cognitive evaluations sdmt auditory verbal learning test avlt daily performance activities daily living adl assessed present study mri scans performed institute neurosurgery tiantan hospital twentyeight matched healthy controls hc mri data obtained tiantan hospital database data thirtyfour points bilateral cortical structure thickness using statistically defined brain regionsofinterest freesurfer obtained participantsresults patients rrms exhibited extensively thinner cerebellar cortex compared hc sdmt scores significantly correlated avlt subentries im immediate memory drm delayed recall memory ltrm longterm recognition memory yarrms patients p 005 sdmt strongly correlated regional cortex thickness differences right temporal pole r 068 bilateral parahippocampal areas right r 062 left r 060 moderately correlated regional cortex thickness differences including left superior temporal right insula r 057 056 respectively yarrms patientsconclusion present study shown sdmt strongly correlated selected cortex regions including bilateral parahippocampal area right temporal pole involved geometric structures processingpmid34280674 doi101016 jclineuro2021106805,1.0
brain 3betahsd upregulation response deteriorating effects background emotional stress animal model multiple sclerosis metab brain dis 2021 mar 15 doi 101007 s11011021007085 online ahead printabstractthe brain 3hydroxysteroid dehydrogenase 3hsd enzyme catalyzes biosynthesis neuroprotective factor progesterone regulation 3hsd response stress exposure cuprizoneinduced model multiple sclerosis investigated reaction related demyelination extremity 32 female wistar rats divided four groups ie control group cont nonstress cuprizone treated ncpz physical stress cuprizone treated pcpz emotional stress cuprizone treated ecpz witness footshock model used induce background stress 5 days elevatedplus maze applied validate stress induction followed 6 weeks cuprizone treatment ymaze test performed confirm brain demyelination 3hsd gene expression indicator progesterone synthesis examined behavioral level stressed groups reflected impaired spatial memory compared ncpz group p 001 severe results ecpz group p 001 results mrna expression 3hsd illustrated significant elevation cuprizone treated groups p 0001 higher upregulation p 0001 ecpz group background stress particularly emotional type exacerbates demyelination caused cuprizone treatment brain upregulates 3hsd gene expression protective response relative myelin degradation extentpmid33721183 doi101007 s11011021007085,1.0
unravelling potential gut microbiota sustaining brain health current prospective towards development neurotherapeutics arch microbiol 2021 mar 24 doi 101007 s00203021022769 online ahead printabstractincreasing incidences neurological disorders parkinsons disease pd multiple sclerosis ms alzheimers disease ad amyotrophic lateral sclerosis als reported insight pathology remains elusive findings suggested gut microbiota play major role regulating brain functions gutbrain axis unique bidirectional communication gut microbiota maintenance brain health play pivotal role regulating incidences neurodegenerative diseases contrarily present life style changing food habits disturbed circadian rhythm may contribute gut homeostatic imbalance dysbiosis leading progression several neurological disorders therefore dysbiosis primary factor behind intestinal disorders may also augment inflammation intestinal bloodbrain barrier permeability microbiotagutbrain axis review primarily focuses gutbrain axis functions specific gut microbial population metabolites produced gut microbiota role regulating various metabolic processes role gut microbiota towards development neurodegenerative diseases however several studies reported decrease abundance specific gut microbial population corresponding increase microbial family findings revealing contradictions reports also showed colonization gut microbiota isolated patients suffering neurodegenerative disease leads development enhance pathological outcomes animal models hence systematic understanding dominant role specific gut microbiome towards development different neurodegenerative diseases possibly provide novel insight use probiotics microbial transplantation substitute approach treating preventing health maladiespmid33763767 doi101007 s00203021022769,0.0
dmts covid19 severity ms pooled analysis italy france ann clin transl neurol 2021 jul 7 doi 101002 acn351408 online ahead printabstractwe evaluated effect dmts covid19 severity patients ms pooledanalysis two large cohorts italy france association baseline characteristics dmts covid19 severity assessed multivariate ordinallogistic models pooled fixedeffect metaanalysis 1066 patients ms italy 721 france included multivariate model anticd20 therapies significantly associated 205 95ci 139302 p 0001 covid19 severity whereas interferon indicated decreased risk 042 95ci 018099 p 0047 pooledanalysis confirms increased risk severe covid19 patients anticd20 therapies supports protective role interferonpmid34240579 doi101002 acn351408,0.0
alemtuzumabinduced alopecia areata case report systematic literature review adverse events associated alemtuzumab j dtsch dermatol ges 2021 may 10 doi 101111 ddg14448 online ahead printabstractalemtuzumab currently approved treatment active relapsingremitting multiple sclerosis rrms despite efficacy therapy several side effects skin noted infusion including vitiligo alopecia areata malignant skin tumors infections awareness effects treatment essential interdisciplinary importance minireview provides overview dermatological side effects described current literature also suggest pathomechanisms underlying phenomena introduce review present case woman rrms developed severe alopecia areata first time alemtuzumabpmid33973347 doi101111 ddg14448,0.0
research progress cd4+t cellsmediated regulation neuroinflammation involved neurodegenerative diseases zhongguo yi xue ke xue yuan xue bao 2021 aug 43 4 628633 doi 103881 jissn1000503x13146abstractneurodegenerative diseases associated neuroinflammation oxidative stress aging can lead cognitive motor dysfunctionsrecent studies suggest development neurodegenerative diseases related adaptive immunity cd4+t cells involved adaptive immune cellsthrough different pathways cd4+t cells differentiate effector regulatory subsets may different effects progression neurodegenerative diseases alzheimers disease parkinsons disease multiple sclerosis amyotrophic lateral sclerosishere review role research progress cd4+t cells neurodegenerative diseasespmid34494536 doi103881 jissn1000503x13146,0.0
progressive leukodystrophylike demyelinating syndromes mogantibodies children rare underrecognized phenotype neuropediatrics 2021 mar 31 doi 101055 s00411726289 online ahead printabstractacquired demyelinating syndromes ads frequently associated myelin oligodendrocytes glycoprotein mog antibodies children clinical phenotypes heterogeneous may delay diagnosis especially relapse atypical mimicking diseases multiple sclerosis neuromyelitis optica spectrum disorders describe two children one progressive cognitive behavioral deterioration seizures one relapse similar clinical impairments associated multiple relapses brain magnetic resonance imaging revealed subsequent progressive leukodystrophylike lesion diffuse bilateral white matter injuries patients cerebrospinal fluid analysis showed pleiocytosis increased level proteins oligoclonal bands metabolic inflammatory blood markers negative brain biopsy performed second child nonspecific inflammatory lesions argument histiocytosis tumor observed clinical radiological stabilization obtained active immunotherapy retrospective analysis antimog antibodies two children positive earlier stage disease turned negative treatment followup leukodystrophylike ads antimogantibodies may display distinct progressive phenotype severe neurological prognosis early diagnosis appropriate treatment may improve outcome childrenpmid33792000 doi101055 s00411726289,1.0
beyond mcdonald updated perspectives mri diagnosis multiple sclerosis expert rev neurother 2021 jul 18 doi 101080 1473717520211957832 online ahead printabstractintroduction magnetic resonance imaging mri essential paraclinical test establish accurate early diagnosis multiple sclerosis ms based application mcdonald criteriaareas covered objective article analyse based publicly available database since publication 2017 mcdonald diagnostic criteria clinical impact criteria discuss potential inclusion within criteria optic nerve demonstrate dissemination space guide acquisition interpretation mri scans diagnostic purposes finally authors will review emerging mri features improve specificity mri diagnosis ms consequently minimize misdiagnosis diseaseexpert opinion although optic nerve included one topographies required demonstrate demyelinating lesion disseminated space 2017 mcdonald criteria new studies seem show improvement sensitivity criteria topography considered new radiological findings central vein sign iron rims considered within typical mri features disease objective minimizing mribased diagnostic errorspmid34275399 doi101080 1473717520211957832,1.0
glatiramer acetate attenuates depressive anxietylike behaviors cognitive deficits induced postweaning social isolation male mice psychopharmacology berl 2021 apr 2 doi 101007 s00213021058365 online ahead printabstractrationale major depressive disorder mdd debilitating disorder adverse effects mood memory quality lifeobjectives study antidepressant potential glatiramer acetate ga drug used management multiple sclerosis investigated acute chronic models depression male mice acute antidepressant screening performed forced swim fst tail suspension tst tests chronic phase postweaning social isolation si used induce depressive anxietylike behaviorsmethods mice reared two different groups social sg isolated ig 4 weeks ig mice treated 05 10 20 mg kg ga last 2 weeks si period animals assessed behavioral tests depression anxiety learning memory hippocampal brainderived neurotrophic factor bdnf level measuredresults acute tests confirmed antidepressant potential ga chronic phase ga reduce immobility time fst p 005 increase exploration activity open field test p 005 increase open arms duration p 005 entries elevated plus maze p0001 improve memory learning passive avoidance test p 005 bdnf level increased ig mice decreased ig mice treated gaconclusions results showed ga improved depressive anxietylike behaviors cognitive dysfunction si reared mice without increasing bdnf level may associated mechanisms actions gapmid33797571 doi101007 s00213021058365,0.0
involvement microrna155 mechanism electroacupuncture treatment effects experimental autoimmune encephalomyelitis int immunopharmacol 2021 jun 3 97107811 doi 101016 jintimp2021107811 online ahead printabstractmultiple sclerosis ms neurodegenerative demyelinating autoimmune disease mediated autoreactive t cells affects central nervous system cns electroacupuncture ea emerged alternative supplemental treatment ms mechanism ea may alleviate ms symptoms unresolved examined effects ea zusanli st36 acupoint mice experimental autoimmune encephalomyelitis eae predominant animal model ms effects ea eae emergence inflammatory cell levels proinflammatory cytokines spinal cord pathology examined ea treatment attenuated eae clinical score associated spinal cord demyelination reducing presence proinflammatory cytokines mononuclear cells mncs downregulating microrna mir 155 upregulating opioid peptide precursor proopiomelanocortin pomc cns experiments cultured neurons transfected mir155 mimic mir155 inhibitor showed direct modulation mir155 levels regulate pomc levels neurons conclusion alleviation eae ea characterized reduced proportions th1 th17 cells increased proportions th2 cells pomc upregulation mir155 downregulation mir155 can suppress pomc expression results support hypothesis effects ea eae may involve downregulation mir155pmid34091117 doi101016 jintimp2021107811,1.0
neuroprotective effect newly synthesized 4aminopyridine derivatives cuprizoneinduced demyelination micea behavioral immunohistochemical study amino acids 2021 jul 8 doi 101007 s00726021030352 online ahead printabstractthe aim study assess effect newly synthesized derivatives 4aminopyridine 4ap cuprizoneinduced model brain demyelination mice 4ap already approved treatment walking difficulties patients multiple sclerosis model demyelination carried administration cuprizone drinking water experimental mice besides cuprizone 4ap derivatives 4ap administered groups order assess protective effect demyelination used immunohistochemistry visualization changes corpus callosum memory storage processes also assessed passive avoidance test last two days experiment experimental mice treated compounds 4b 4c increased significantly latency time second day comparison control group indicated improved memory process number mature oligodendrocytes groups treated compounds 4b 4c 4ap closer control group results studies showed newly synthesized compounds 4b 4c reverse effect cuprizone groups also showed increased latency time passive avoidance test comparison control grouppmid34240251 doi101007 s00726021030352,1.0
evolution understanding mscovid19 interactions concerns vaccination j clin neurosci 2021 aug 90132134 doi 101016 jjocn202105063 epub 2021 jun 1abstractas news approval covid19 vaccination emerge neurologists across globe ponder upon whether use immunotherapies patients multiple sclerosis ms paper highlights mechanism various disease modifying therapies dmts well recently approved pfizer moderna vaccines covid19 well guidelines introduced national multiple sclerosis society mechanisms counteract molecular level believe evidence data might lay foundation formulate much needed recommendations usage medications vaccinating ms patients dmtspmid34275536 doi101016 jjocn202105063,0.0
covid19 vaccination patients multiple sclerosis diseasemodifying therapy neurol clin pract 2021 aug 11 4 358361 doi 101212 cpj0000000000001088abstractthe covid19 pandemic resulted challenges practice neurology one major concern best manage patients multiple sclerosis ms diseasemodifying therapies dmts dmts frequently immunosuppressive properties increase risk covid19 potentially reduce immunologic response vaccination group already vulnerable infection due neurologic deficits review early data covid19 outcomes patients ms discuss known vaccine effectiveness anticd20 sphingosine1phosphate receptor agents proposed attenuating effects based mechanisms action addition provide recommendations best use novel covid19 vaccines population highlight information may better inform vaccine strategies futurepmid34484934 pmcpmc8382390 doi101212 cpj0000000000001088,0.0
pilot trial autologous hematopoietic stem cell transplant neuromyelitis optic spectrum disorder mult scler relat disord 2021 may 4 53102990 doi 101016 jmsard2021102990 online ahead printabstractbackground autologous hematopoietic stem cell transplantation ahsct become standard treatment multiple sclerosis role ahsct neuromyelitis optica spectrum disorder nmo nmosd unclear studied ahsct nmo nmosd patients failed conventional immunosuppressive therapymethods eligible patients received ahsct cyclophosphamide rabbit antithymocyte globulin rituximab followed five years primary outcome relapsefree status year three additional outcomes included relapse status year five relapse rate edss mri activity overall survivalresults 20102016 three patients enrolled one patient evidence disease activity 10 years one improvement relapse rate edss breakthrough clinically radiologically requiring rituximab year five third died year 35 due uncontrollable nmosd relapses accumulation marked disabilityconclusion trial ahsct appeared safe moderately effective two three patients showing improvement disease activity disability future studies undertaken determine ideal ahsct conditioning characteristics patients likely enter longterm remissionpmid34082329 doi101016 jmsard2021102990,0.0
explaining individual challenges women affected neuromyelitis optica multiple sclerosis comparative content analysis study clin neurol neurosurg 2021 jun 26 207106789 doi 101016 jclineuro2021106789 online ahead printabstractintroduction multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd autoimmune condition unexpected acute relapses aim qualitative study explaining individual problems experienced women affected nmosd msmethod sixteen nmosd patients eighteen ms patients completed face face deep semistructured interview participants recruited ms ward sina hospital typing interview data analyzed using conventional content analysis recommended graneheim lundman 2005 data analysis managed maxqda2018 softwareresults study common theme disease groups identified challenges arising personal problems categories named many similarities nmosd group include four categories including uncertainty perception threat living limitations active coping normalization facilitators personal problems appeared group patients ms five categories emerged perceived threat living bottleneck trying deal negative experiences facilitators personal problems problems related physical rehabilitationconclusion qualitative study showed individual problems two groups nmosd ms patients somewhat similar also present study people ms need longerterm rehabilitation care people nmosd considered examined need less seen people nmosd unpredictability relapse nmosd ms can profound effect daily lives people therefore knowing health life problems patients nmosd ms can help health care teams improve quality patient carepmid34214870 doi101016 jclineuro2021106789,0.0
fair equitable treatment multiple sclerosis resourcepoor regions need offlabel therapies regional treatment guidelines mult scler 2021 aug 27 9 13201322 doi 101177 13524585211028806no abstractpmid34374317 doi101177 13524585211028806,0.0
treatment patterns following initiation generic glatiramer acetate among patients multiple sclerosis two large realworld databases united states curr med res opin 2021 may 181 doi 101080 0300799520211929135 online ahead printabstractintroduction better understand treatment patterns us patients multiple sclerosis ms initiating generic glatiramer acetate ga study examined adherence discontinuation switching patterns generic followon glatiramer acetate foga therapy realworld patient cohortsmethods retrospective analyses utilized data two large us databases administrative claims linked electronic medical records eligible adult ms patients 1 pharmacy claim foga identification period first foga claim index date analyses descriptive proportion days covered pdc calculated measure adherence foga followup periodresults first cohort consisted 95 patients 936 branded ga claim copaxone baseline period half patients 484 high adherence foga therapy pdc 0810 fiftyfive patients 579 initially discontinued foga mean persistence 112 days discontinued 73 subsequent diseasemodifying therapy dmt 309 restarted foga 618 restart foga second cohort consisted 1 957 patients 638 branded ga claim copaxone baseline period 335 treatment nave majority patients 619 high adherence foga therapy 1 597 patients 816 initially discontinued foga mean persistence 93 days discontinued 558 switched another dmt 167 restarted foga 375 subsequent dmtconclusion adherence foga therapy reasonably high across cohorts however patients discontinued initial foga within four months index date switches foga branded ga productspmid34003068 doi101080 0300799520211929135,0.0
nutrition information resources used people systemic sclerosis perceived advantages disadvantages nominal group technique study acr open rheumatol 2021 jul 1 doi 101002 acr211293 online ahead printabstractobjective people systemic sclerosis ssc scleroderma obtain diet nutrition information manage disease known objectives identify 1 resources used people ssc nutrition diet information 2 perceived advantages disadvantages resourcesmethods conducted nominal group technique ngt sessions people ssc reported nutrition diet information resources used perceived advantages disadvantages accessing using resources participants indicated whether tried resource rated helpfulness importance possible advantages disadvantages items elicited across sessions merged eliminate overlapresults conducted four ngt sessions three english language one french language 15 total participants identified 33 unique information resources 147 resourcespecific advantages 118 resourcespecific disadvantages resource categories included health care providers alternative complementary practitioners websites media platforms events print materials common themes advantages disadvantages included quality individualization information accessibility resources terms cost location comprehensibility information provided medical professionals regarded credible can obtained books articles websites individual consultation easily accessible webbased information considered highly accessible although variable credibility inperson events may important source health information people sscconclusion people ssc obtain nutrition diet information multiple resources seek credible accessible resources provide sscspecific individualized informationpmid34196508 doi101002 acr211293,0.0
chronic active lesions new mri biomarker monitor treatment effect multiple sclerosis expert rev neurother 2021 jul 8 doi 101080 1473717520211953983 online ahead printno abstractpmid34236010 doi101080 1473717520211953983,0.0
spinal fluid myeloid microvesicles predict disease course multiple sclerosis ann neurol 2021 jul 3 doi 101002 ana26154 online ahead printabstractobjective vivo measures myeloid activity promising biomarkers multiple sclerosis previously demonstrated csf myeloid microvesicles markers microglial macrophage activity neuroinflammation multiple sclerosis aimed investigating diagnostic prognostic value myeloid microvesicles clinical settingmethods sixhundredone patients discharged diagnosis neuroinflammatory neurodegenerative neurological disease enrolled myeloid microvesicles measured flowcytometry ib4+ events fresh csf clinical demographical mri data collected diagnosis patients followup n176 results csf myeloid microvesicles elevated neuroinflammatory patients compared neurodegenerative control group multiple sclerosis microvesicles higher patients mri disease activity concentration increased along enhancing lesions number p00001 jonckheereterpstra csf myeloid microvesicles also higher patients higher disease activity month year preceding diagnosis microvesicles excellently discriminated relapsingremitting control group roc curve auc0939 p00001 radiologically isolated syndrome unspecific brain lesions 0942 p00001 furthermore microvesicles independent predictors prognosis relapsingremitting progressive groups microvesicles independently predict future disease activity relapsingremitting patients hr1967 ci95 11473372 correcting prognostic factors standard clinical use progressive group microvesicles independent predictors disability accrual hr10767 ci95 133586812 interpretation results confirm csf myeloid microvesicles clinically meaningful biomarker neuroinflammation microglial macrophage activity vivo findings may support possible use clinical practice diagnostic workup prognostic assessment article protected copyright rights reservedpmid34216397 doi101002 ana26154,1.0
depression individuals multiple sclerosis social media use interlinked acta neurol belg 2021 mar 20 doi 101007 s13760021016568 online ahead printno abstractpmid33743162 doi101007 s13760021016568,0.0
scoring 10year risk ambulatory disability multiple sclerosis road score eur j neurol 2021 mar 31 doi 101111 ene14845 online ahead printabstractbackground baseline prognostic factors shortterm predictors treatment response can influence longterm risk disability accumulation patients relapsingremitting multiple sclerosis rrms objective develop validate scoring system combining baseline prognostic factors oneyear variables treatment response single numeric score predicting longterm risk disabilitymethods analyzed two independent datasets patients rrms started interferon beta glatiramer acetate expanded disability status scale edss score 40 treatment start followed least 10 years first dataset training set included patients attending three ms centers italy served framework create socalled road score risk ambulatory disability second validation set included cohort patients followed barcelona spain explore performance road score predicting risk reaching edss score60results road score derived training set n 1 225 based demographic age clinical baseline prognostic factors disease duration edss oneyear predictors treatment response number relapses presence gadoliniumenhancement new t2 lesions best cutoff score discriminating patients higher risk reaching disability milestone 4 applied validation set n 296 patients road score 4 approximately 4fold increased risk reaching disability milestone p0001 discussion propose road score useful tool predict individual prognosis patients rrms optimize treatment strategypmid33786942 doi101111 ene14845,0.0
medication costs harm patients multiple sclerosis neurol clin pract 2021 aug 11 4 269270 doi 101212 cpj0000000000000927no abstractpmid34484924 pmcpmc8382395 doi101212 cpj0000000000000927,0.0
sarcoidosis neuromyelitis optica patient optic neuritis case report ann clin transl neurol 2021 jun 24 doi 101002 acn351413 online ahead printabstractwe present case atypical recurrent optic neuritis man 50s presented right optic neuritis profound visual loss associated elevated inflammatory markers lymphnode biopsy consistent sarcoidosis aquaporin4 antibodies also present three months following corticosteroid treatment right optic neuritis relapsed raised inflammatory markers started azathioprine prednisolone good effect dual diagnosis sarcoidosis neuromyelitis optica aquaporin4 antibodies rare longterm immunosuppression required case highlights importance identifying features cause atypical optic neuritispmid34166585 doi101002 acn351413,0.0
emerging role pd1 central nervous system brain diseases neurosci bull 2021 apr 20 doi 101007 s1226402100683y online ahead printabstractprogrammed cell death protein 1 pd1 immune checkpoint modulator major target immunotherapy antipd1 monoclonal antibodies demonstrated remarkable efficacy cancer treatment accumulating evidence suggests important role pd1 central nervous system cns pd1 implicated cns disorders brain tumors alzheimers disease ischemic stroke spinal cord injury multiple sclerosis cognitive function pain pd1 signaling suppresses cns immune response via resident microglia infiltrating peripheral immune cells notably pd1 also widely expressed neurons suppresses neuronal activity via downstream src homology 2 domaincontaining protein tyrosine phosphatase 1 modulation ion channel function improved understanding pd1 signaling crosstalk glial cells neurons peripheral immune cells cns will shed light immunomodulation neuromodulation novel strategies treating brain diseasespmid33877518 doi101007 s1226402100683y,0.0
patient perceptions fda approval gaps education variation values neurol clin pract 2021 aug 11 4 273279 doi 101212 cpj0000000000001034abstractobjective assess perceptions opinions food drug administration fda approval process diseasemodifying therapies dmt people living multiple sclerosis ms methods people living ms invited complete webbased survey perceptions fda role process approval ms medications survey asked role fda factors involved approval process voices represent ms deliberations drug approval level comfort uncertain safety newly approved therapiesresults three thousand thirtythree respondents met inclusion criteria data analysis respondents seemed understand role fda although half understood fundamental fda role balancing risks benefits considering drug approval significant differences observed many areas tried dmts comfort uncertainty associated several factors relating side effects benefits believed important fda consider respondents reported people participated medications clinical trial particularly able represent people living msconclusion perceptions regarding fda views represent people living ms varied tried dmt variability personal values recognized taken account considering regulatory responsibilities interventions needed address educational gaps regarding mission trustworthiness fda oversight bodypmid34484926 pmcpmc8382396 doi101212 cpj0000000000001034,0.0
impairment vestibulocollic reflex linear vestibuloocular reflex pediatriconset multiple sclerosis patients clin neurophysiol 2021 may 24 132 8 18131819 doi 101016 jclinph202104014 online ahead printabstractobjectives study aimed examine vestibulocollic reflex vcr linear vestibuloocular reflex lvor correlation brain lesions pediatriconset multiple sclerosis poms methods study group consisted 17 patients 34 ears poms mean age 1873 202 mean age disease onset 1464 136 years control group included 11 agematched healthy subjects 22 ears ocular cervical vestibular evoked myogenic potentials ovemp cvemp performed assess ivor vcr pathways magnetic resonance imaging evaluated study groupresults poms group 4705 ovemps 1764 cvemps abnormal vemps normal control group ovemp amplitude associated infratentorial lesion volume r 0459 p 001 total lesion volume brainstem cerebellum r 0450 p 001 cvemp asymmetry ratio correlated deep white matter lesion volume r 0683 p 0001 mvemp scores found correlate lesion volumes cerebellum r 0488 p 004 infratentorial region r 0573 p 001 conclusions ocular cervical vemp abnormalities confirm lvor vcr pathways may affected early pomssignificance routine use vemp test especially ovemp test recommended useful tool followup poms patientspmid34130249 doi101016 jclinph202104014,0.0
ebi2 expressed glial cells multiple sclerosis lesions knockout modulates remyelination cuprizone model eur j neurosci 2021 jun 19 doi 101111 ejn15359 online ahead printabstractebi2 receptor regulates immune system multiple sclerosis upregulated central nervous system infiltrating lymphocytes newborn ebi2deficient mice myelin development delayed persistent antagonism inhibits remyelination chemicallydemyelinated organotypic cerebellar slices used cuprizone model multiple sclerosis elucidate role central nervous systemexpressed ebi2 de remyelination wildtype ebi2 knockout mice fed 02 cuprizone chow five weeks allowed recover normal diet two weeks data showed less efficient recovery myelin attenuated oligodendrocyte loss fewer astrocytes increased total cholesterol levels ebi2 knockout mice recovery moreover wildtype mice upregulated ebi2 expression recovery confirming involvement ebi2 signalling recovery demyelination cuprizone model proinflammatory cytokine levels comparable levels wildtype ebi2 knockout mice minor differences tnf il1 levels either peak recovery neuroinflammatory signalling molecules abl1 kinase nfb1 p105 p50 subunit significantly downregulated ebi2 knockout mice peak disease immunohistochemical investigations ebi2 receptor distribution cns cells ms brain revealed strong expression ebi2 astrocytes microglia inside plaques implicating gliaexpressed ebi2 multiple sclerosis pathophysiology taken together findings demonstrate involvement ebi2 signalling recovery demyelination rather demyelination warrant research role ebi2 remyelinationpmid34145920 doi101111 ejn15359,1.0
demyelination result immune response patients covid19 acta neurol belg 2021 may 2 doi 101007 s13760021016915 online ahead printabstractthe coronavirus disease 2019 covid19 caused severe acute respiratory syndrome coronavirus2 sars cov2 already appeared global pandemic presentation disease often includes upper respiratory symptoms like dry cough dyspnea chest pain rhinorrhea can develop respiratory failure needing intubation furthermore occurrence acute subacute neurological manifestations stroke encephalitis headache seizures frequently stated patients covid19 one reported neurological complications severe covid19 demolition myelin sheath indeed complex immunological dysfunction provides substrate development demyelination nevertheless published reports literature describe demyelination subjects covid19 short narrative review discuss probable pathological mechanisms may trigger demyelination patients sarscov2 infection summarize clinical evidence confirming sarscov2 condition risk factor destruction myelinpmid33934300 doi101007 s13760021016915,1.0
tlr2 tlr3activated microglia induce different levels neuronal network dysfunction contextdependent manner brain behav immun 2021 may 17s08891591 21 00194x doi 101016 jbbi202105013 online ahead printabstractrecognition pathogen damageassociated molecular patterns pamps damps innate tolllike receptors tlrs central activation microglia brain macrophages many cns diseases notably tlrmediated microglial activation complex modulated additional exogenous endogenous immunological signals impact different microglial reactive phenotypes electrical activity neurotransmission widely unknown however explored effects tlr ligands microglia neuronal network function rat organotypic hippocampal slice cultures situ ie postnatal cortical tissue lacking adaptive immunity single exposure slice cultures tlr2 tlr3 ligands pgn poly ic 23 days induced moderate microglial activation featuring il6 tnf release mild alterations fast neuronal gamma band oscillations 3070 hz fundamental higher cognitive functions perception memory behavior paired exposure tlr3 tlr2 tlr3 tlr4 ligands lps induced nitric oxide release enhanced tnf release associated advanced network dysfunction including slowing beta frequency band 1230 hz neural bursts hyperexcitability paired exposure tlr ligand leukocyte cytokine ifn enhanced release associated severe network dysfunction albeit parvalbumin somatostatinpositive inhibitory interneurons preserved notably neuronal disturbance prevented either microglial depletion pharmacological inhibition oxidantproducing enzymes inducible synthase inos nadph oxidase conclusion tlractivated microglia can induce different levels neuronal network dysfunction severe dysfunction mainly caused reactive oxygen nitrogen species rather proinflammatory cytokines findings provide mechanistic insight microglial activation functional neuronal network impairment relevance neuroinflammation neurodegeneration observed eg meningoencephalitis multiple sclerosis alzheimers diseasepmid34015428 doi101016 jbbi202105013,0.0
dancing larynx syndrome associated trigeminal neuralgia secondary multiple sclerosis neurol clin pract 2021 aug 11 4 e544e545 doi 101212 cpj0000000000000972no abstractpmid34484953 pmcpmc8382412 doi101212 cpj0000000000000972,0.0
multiple sclerosis symptoms vary age sex race ethnicity neurol clin pract 2021 aug 11 4 335341 doi 101212 cpj0000000000001105abstractobjective little known symptom severity various neurologic domains commonly affected multiple sclerosis ms varies age sex race ethnicitymethods retrospective study patients ms attending 2 tertiary centers new york city metropolitan area selfidentified white african american aa hispanic american ha disability rated patientdetermined disability steps pdds symptom severity symptomscreen syms validated battery assessing symptoms 12 domains analyses comparing race sex age groups performed using analysis variance models tukey honestly significant difference tests control overall type error multivariable model constructed predict good selfrated health srh included demographic variables pdds syms domain scoresresults sample consisted 2 622 patients ms age 464 years 736 female 664 white 217 aa 119 ha men higher adjusted pdds women p 0012 similar total syms scores women reported higher fatigue anxiety scores whereas men higher walking dexterity scores aas higher symptom domain scores whites 12 domains worse srh multivariable logistic model pain walking depression fatigue global disability pdds sex race ethnicity predicted good srhconclusions aa ha race ethnicity associated higher overall disability higher symptom severity 12 domains commonly affected ms worse srh relative whites however symptom severity disability demographic variables predicted good srhpmid34476125 pmcpmc8382423 doi101212 cpj0000000000001105,0.0
coculture exogenous oligodendrocytes unmyelinated cerebella revisiting ex vivo models new tools study myelination glia 2021 apr 2 doi 101002 glia24001 online ahead printabstractcommon vitro models used study mechanisms regulating myelination rely cocultures oligodendrocyte precursor cells opcs neurons models myelination occurs environment fully reflect cellcell interactions environmental cues present vivo avoid limitations specifically manipulating oligodendroglial cells developed reliable ex vivo model myelination seeding opcs cerebellar slices deprived endogenous oligodendrocytes showed exogenous opcs seeded unmyelinated cerebella efficiently differentiate form compact myelin spectral confocal reflectance microscopy electron microscopy analysis revealed density compacted myelin sheaths highly increases along culture importantly defined appropriate culture time frame study opc differentiation myelination using accurate quantification resources generated thus model powerful tool study cellular molecular mechanisms opc differentiation myelination moreover suitable development validation new therapies myelinrelated disorders multiple sclerosis psychiatric diseasespmid33811384 doi101002 glia24001,1.0
ilc chronic inflammation cancer targeting biologicals mol aspects med 2021 mar 14100963 doi 101016 jmam2021100963 online ahead printabstractsince discovery innate lymphoid cells ilc emerged important effector cells serving multiple roles maintaining tissue homeostasis responding tissue insults dysregulations function distribution observed variety immunemediated diseases suggesting specific role ilc pathophysiology several disorders including chronic inflammation cancer provide updated view ilc biology dissecting pathological protective contribution chronic inflammatory diseases multiple sclerosis inflammatory bowel diseases psoriasis rheumatoid arthritis asthma copd atherosclerosis also exploring ilc role tumor surveillance progression throughout review will also highlight potential dual role cells protective pathogenic immunity many inflammatory diseases makes interesting targets development novel therapeutic strategies particularly promisingpmid33726947 doi101016 jmam2021100963,0.0
engineered cytokines cancer autoimmune disease immunotherapy adv healthc mater 2021 mar 9e2002214 doi 101002 adhm202002214 online ahead printabstractcytokine signaling critical range biological processes including cell development tissue repair aging immunity addition acting key signal mediators immune system cytokines can also serve potent immunotherapies 20 recombinant products currently food drug administration fda approved treat conditions including hepatitis multiple sclerosis arthritis various cancers yet despite biological importance clinical utility cytokine immunotherapies suffer intrinsic challenges limit therapeutic potential including poor circulation systemic toxicity low tissue cellspecificity past decade particular methods devised engineer cytokines order overcome challenges myriad strategies reviewed may employed order improve therapeutic potential cytokine chemokine immunotherapies applications cancer autoimmune disease therapy well tissue engineering regenerative medicine clarity strategies collected presented vary across size scales ranging single amino acid substitutions larger proteinpolymer conjugates nano micrometerscale particles macroscale implants together work aims provide readers timely view field cytokine engineering emphasis earlystage therapeutic approachespmid33690997 doi101002 adhm202002214,0.0
well people living neurodegenerative diseases manage finances metaanalysis systematic review capacity make financial decisions people living neurodegenerative diseases neurosci biobehav rev 2021 may 28 127709739 doi 101016 jneubiorev202105021 online ahead printabstractself proxy reported questionnaires indicate people living neurodegenerative disease ndd difficulties financial decisionmaking fdm healthy controls selfreports however rely adequate insight everyday functioning might therefore less reliable present study provides comprehensive overview metaanalysis studies evaluating fdm people living ndd reliability performancebased tests consistently identify fdm difficulties people living ndd compared healthy controls evaluated furthermore associations fdm disease severity performances standard measures cognition demographics evaluated 47 included articles consistently reported lower performances performancebased fdm tests people living ndd including alzheimers disease mild cognitive impairment frontotemporal dementia parkinsons disease multiple sclerosis huntingtons disease compared healthy controls majority studies however focused alzheimers disease mild cognitive impairment k 38 fdm performance appears related cognitive decline specifically working memory processing speed numeracypmid34058557 doi101016 jneubiorev202105021,0.0
home infusions natalizumab people multiple sclerosis pilot randomised crossover trial ann clin transl neurol 2021 jul 21 doi 101002 acn351410 online ahead printabstractobjective delivery healthcare home expanded intravenous infusions monoclonal antibodies recently developed model care home infusions natalizumab people relapsingremitting multiple sclerosis evaluated pilot study home infusions natalizumab usual care attendance hospital outpatients clinic compared safety feasibility patient satisfaction effectiveness costsmethods randomised ab ba crossover trial 37 adults randomised usual care n 19 home infusions n 18 three infusions patients crossed alternate treatment another three infusions patient safety outcomes adherence satisfaction quality life disability costs comparedresults adverse events recorded 207 infusions 35 patients across home clinic infusions difference adherence p 071 infection rates p 084 home clinic settings satisfaction convenience home infusions significantly greater p 0008 differences quality life measures excluding pharmacy costs a74 lower per infusion home including a16 patients outofpocket costsinterpretation differences safety effectiveness clinic home infusions natalizumab home infusions shown feasible convenient less expensive usual care larger scale studies required verify preliminary findings particularly around safety management hypersensitivity adverse events home setting equivalence clinical outcomespmid34288591 doi101002 acn351410,0.0
xray myelin trends neurosci 2021 jun 17s01662236 21 001144 doi 101016 jtins202106002 online ahead printabstractwith substantial progress experimental therapeutics enhance nervous systems capacity remyelination new methods detect myelin important advances discuss smallangle xray scattering tensor tomography approach presented recently georgiadis et al methods promise providing new window brain evaluate myelin integrity health diseasepmid34148671 doi101016 jtins202106002,1.0
pregnancy outcomes alemtuzumab treated women multiple sclerosis case series neurol sci 2021 apr 15 doi 101007 s10072020049755 online ahead printabstractdata pregnancy outcome alemtuzumabtreated women scarce derived safety reports clinical trials report seven women overall eight pregnancies treatment alemtuzumab realworld setting pregnancies occurred within 9 months alemtuzumab treatment two within 4 months despite patients informed pregnancy prevention found one congenital cytomegalovirus infection one spontaneous abortion one elective abortion due extrauterine pregnancy five live births without congenital abnormalities birth defectspmid33860394 doi101007 s10072020049755,0.0
rct telehealth groupbased intervention increase physical activity multiple sclerosis efit neurol clin pract 2021 aug 11 4 291297 doi 101212 cpj0000000000001039abstractobjective conduct pilot randomized controlled trial determine whether participation groupbased structured telehealth intervention increases physical activity people multiple sclerosis ms methods parallelarms trial study procedures administered remotely adults diagnosed ms subtype randomized one two 12week 1 h wk active conditions efit online moderated structured groups ejournal online independent journaling comparison treatmentasusual tau ie efit ejournal group enrolled primary outcome feasibility completion adherence secondary efficacy outcomes included selfreported physical activity level international physical activity questionnaire ipaq results participants 37 adults ms sample diverse 667 female age range 2364 years 175 hispanic 125 black progressive relapsingremitting disease subtypes regarding feasibility 707 completed average adherence 749 physical activity active groups increased 342 baseline ipaq 2 4068 1 9597 followup 3 2294 2 5752 decreased tau group 174 baseline 2 5199 1 5001 followup 2 0812 1 8149 group time interaction statistically significant f 2 25 1467 p 0250 partial 2 0105 conclusions telehealth represents accessible acceptable vehicle deliver targeted behavioral treatments neurologic population efit may effective intervention increasing physical activity historically intractable treatment target individuals ms addition results provide evidence feasibility conducting fully remote clinical trial researchclassification evidence study provides class ii evidence people ms participation groupbased structured telehealth intervention compared tau resulted nonsignificant increase selfreported physical activity level percentage participants completed followup questionnaires differ groups trial registered clinicaltrialsgov nct03829267 pmid34484928 pmcpmc8382401 doi101212 cpj0000000000001039,0.0
barriers facilitators employment comparison participants multiple sclerosis spinal cord injury arch phys med rehabil 2021 mar 5s00039993 21 002227 doi 101016 japmr202102015 online ahead printabstractobjective compare selfreported barriers facilitators employment among employed unemployed participants multiple sclerosis ms spinal cord injury sci design crosssectional using selfreport assessment obtained mail onlinesetting medical university southeastern usaparticipants total 2 624 participants including 1 234 ms 1 390 sci identified either specialty hospital statebased surveillance system southeastern usa age 65 time assessmentinterventions n main outcome measures selfreported barriers facilitators employmentresults overall ms participants reported barriers particularly stress cognition fatigue whereas sci likely report proper education training resources transportation attendant care followup analyses broken employment status indicated several barriers facilitators significantly related diagnosis either employed unemployed participants among employed sci likely report types jobs presci ms likely state know much jobs people disabilities differences noted variables among unemployed unemployed individuals sci likely report jobs trained accessibleconclusions primary barriers people ms revolve around condition whereas sci appear related modifiable factors vocational rehabilitation specialists need identify diagnostic specific barriers promote employment outcomespmid33684369 doi101016 japmr202102015,0.0
association vitamin d acute rejection human kidney transplantation systematic review metaanalysis study transpl immunol 2021 may 18101410 doi 101016 jtrim2021101410 online ahead printabstractbackground vitamin d vitd deficiency associated several diseases multiple sclerosis rheumatoid arthritis respiratory infection forth field transplantation kidney transplantation studies reported patients vitd deficiency increased chance acute rejection studies show chance hand since vitd modulatory factor can reduce inflammatory response understanding exact role transplantation may contribute tolerance condition patientsmethods electronic databases including pubmed scopus embase proquest web science google scholar searched eligible studies general 14 studies total 4770 patients included metaanalysis regarding methodological heterogeneity selected randomeffects combination model moreover chosen effect size studyresults combination 14 studies showed patients vitddeficient group 82 increased chance acute rejection compared patients vitdsufficient group effect significant 182 95 confidence interval ci 129 256 i2 523 result significant regarding narrow ci can conclusive result study quality gender variables main sources inconsistent results primary studies moreover using metaregression showed vitd deficiency independent estimated glomerular filtration rate egfr patients increased chance acute rejectionconclusion normal vitd status patients days transplantation can reduce chance acute rejectionpmid34020044 doi101016 jtrim2021101410,0.0
covid19 patients myasthenia gravis epidemiology disease course muscle nerve 2021 may 24 doi 101002 mus27324 online ahead printabstractintroduction covid19 disease caused sarscov2 infection become global pandemic patients myasthenia gravis mg often treated immunosuppressants might higher risk developing covid19 demonstrating severe disease course aimed study prevalence describe features covid19 mg patientsmethods may 2020 conducted telephonic interviews mg patients followed referral center collected structured data regarding mg covid19 diagnosed probable confirmed according european centre disease prevention control case definition compared confirmedcovid19 prevalence calculated beginning pandemic mg patients overall pavia districtresults interviewed 162 mg patients median age 66 years interquartile range 4177 males 599 88 pavia district three patients sarscov2confirmed pcr 8 probablecovid19 pavia district prevalence confirmedcovid19 among mg patients 1 88 114 overall population 4 777 546 515 087 differ p0538 higher mgfa class need recent rescue treatment ongoing immunosuppressive treatments associated covid19 risk three 11 mg patients probable confirmedcovid19 required ventilator support 2 elderly patients died covid19 respiratory insufficiency 1 11 patients experienced worsening mg symptoms improved increasing steroid dosediscussion risk covid19 mg patients seems higher general population regardless immunosuppressive therapies cohort covid19 barely affected mg coursepmid34031902 doi101002 mus27324,0.0
docosahexaenoic acid ameliorates autoimmune inflammation activating gpr120 signaling pathway dendritic cells int immunopharmacol 2021 apr 28 97107698 doi 101016 jintimp2021107698 online ahead printabstractalthough phenomenon omega3 polyunsaturated fatty acids n3 pufas shows beneficial effect patients suffering multiple sclerosis ms autoimmune diseases empirically welldocumented molecular mechanisms underline antiinflammatory effects n3 pufas yet understood experimental autoimmune encephalomyelitis eae model ms show one underlying mechanisms dietary docosahexaenoic acid dha exerts antiinflammatory effect regulating functional activities dendritic cells dcs dhatreated eae mice dcs acquire regulatory phenotype characterized low expression costimulatory molecules decreased production proinflammatory cytokines enhanced capability regulatory tcell induction effect dha dcs mediated lipidsensing receptor g proteincoupled receptor 120 gpr120 gpr120specific smallmolecule agonist ameliorate autoimmune inflammation regulating dcs silencing gpr120 dcs strongly increased immunogenicity dcs stimulation gpr120 induces suppressor cytokine signaling 3 socs3 expression downregulates signal transducer activator transcription 3 stat3 phosphorylation explaining molecular mechanism regulatory dc inductionpmid33932699 doi101016 jintimp2021107698,0.0
dynamic nanoassemblies imaging therapy neurological disorders adv drug deliv rev 2021 jun 16113832 doi 101016 jaddr2021113832 online ahead printabstractthe past decades witnessed increased incidence neurological disorders nds alzheimers disease parkinsons disease huntingtons disease amyotrophic lateral sclerosis ischemic stroke epilepsy significantly lower patients life quality increase economic social burden recently nanomedicines composed imaging therapeutic agents explored diagnose treat nds due enhanced bioavailability bloodbrain barrier bbb permeability targeting capacity intriguingly dynamic nanoassemblies selfassembled functional nanoparticles simultaneously interfere multiple pathogenic substances pathological changes regarded one foremost candidates improve diagnostic therapeutic efficacy nds help readers better understand emerging field review pathogenic mechanism different types nds briefly introduced functional nanoparticles used building blocks construction dynamic nanoassemblies nds theranostics summarized furthermore dynamic nanoassemblies can actively cross bbb target brain lesions sensitively efficiently diagnose treat nds effectively promote neuroregeneration highlighted finally conclude perspectives future development fieldpmid34146626 doi101016 jaddr2021113832,0.0
singlecell atlas hepatic t cells reveals expansion liverresident naivelike cd4+ t cells primary sclerosing cholangitis j hepatol 2021 mar 24s01688278 21 002191 doi 101016 jjhep202103016 online ahead printabstractbackground aims little known composition intrahepatic immune cells contribution pathogenesis primary sclerosing cholangitis psc aimed create atlas intrahepatic t cells thereby detail characterize t cells human inflamed livermethods different singlecell rna sequencing methods combined silico analyses intrahepatic peripheral t cells patients psc n11 healthy donors hd n4 multiparameter flow cytometry functional vitro experiments conducted patients psc n24 controls hcv n5 nash n3 ald n16 lrm n10 hd n10 results present landscape intrahepatic t cells psc reveal population intrahepatic naivelike cd4+ t cells present liver diseases tested particularly expanded psc population transcriptome t cell receptor repertoire similar circulating naive t cells expressed set genes associated tissue residency periductal location supported concept tissueresident naivelike t cells livers patients psc trajectory inference suggested developmental propensity cells acquire th17 polarizationstate functional chromatin accessibility experiments revealed predisposition circulating naive t cells patients psc polarize towards th17 cellsconclusion report first atlas intrahepatic t cells psc led identification previously unrecognized population tissueresident naivelike t cells inflamed human liver finding naive cd4+ t cells psc harbour propensity develop th17 cellslay summary composition intrahepatic immune cells primary sclerosing cholangitis psc contribution disease pathogenesis widely unknown generated singlecell atlas intrahepatic t cells psc type immune cells previously involved pathogenesis psc atlas provides valuable data source field using atlas identified population liverresident naivelike cd4+ t cells expanded livers patients psc compared healthy liver tissue liver diseases trajectory inference suggest cells propensity acquire th17associated effector functions since th17polarized cells considered contribute development psc findings point towards far underestimated role naive t cells pscpmid33774059 doi101016 jjhep202103016,0.0
evaluating effects transcutaneous tibial nerve stimulation pelvic floor muscle training sexual dysfunction female multiple sclerosis patients reporting overactive bladder neurourol urodyn 2021 jun 26 doi 101002 nau24733 online ahead printabstractaims sexual dysfunction sd common female patients multiple sclerosis ms reporting overactive bladder oab symptoms aim study evaluate effects transcutaneous tibial nerve stimulation ttns pelvic floor muscle training pfmt biofeedback sd female patients ms reporting oab symptomsmethods patients overactive bladder sd allocated receive ttns pfmt daily overactive bladder symptoms sexual functions sexual quality life assessed baseline 6th weeks female sexual function index fsfi overactive bladder questionnaire oabv8 sexual quality lifefemale sqolf questionnaires usedresults thirty patients ttns 10 pfmt 20 included study compared baseline total fsfioabv8 sqolf scores improved ttns p 0005 p 0011 p 0444 respectively pfmt p 0002 p 0001 p 0001 respectively groups betweengroup comparisons show significant differencesconclusion study demonstrates efficacy ttns pfmt improving sexual function female ms patients oab symptoms show superiority particular method studies required investigate differences two noninvasive methodspmid34174117 doi101002 nau24733,0.0
multiple sclerosis treatment consensus group mstcg position paper diseasemodifying treatment multiple sclerosis 2021 white paper nervenarzt 2021 jul 23 doi 101007 s00115021011572 online ahead printabstractmultiple sclerosis complex autoimmunemediated disease central nervous system characterized inflammatory demyelination axonal neuronal damage approval various diseasemodifying therapies increased understanding disease mechanisms evolution recent years significantly changed prognosis course disease update multiple sclerosis therapy consensus group treatment recommendation focuses important recommendations diseasemodifying therapies multiple sclerosis 2021 recommendations based current scientific evidence apply medications approved wide parts europe particularly germanspeaking countries germany austria switzerland pmid34297142 doi101007 s00115021011572,1.0
changes leptin serotonin cortisol eight weeks aerobic exercise probiotic intake cuprizoneinduced demyelination mouse model multiple sclerosis cytokine 2021 may 24 144155590 doi 101016 jcyto2021155590 online ahead printabstractbackground multiple sclerosis ms common nontraumatic neurological cause disability young adults physical activity particularly exercise training evidencebased approach managing symptoms restoring function improving overall wellness people ms well use probiotics can effective reducing damage inflammation ms patientsobjective study aimed address changes leptin serotonin cortisol following eight weeks aerobic exercise along probiotic intake cuprizoneinduced demyelination mouse model msmethods mice exposed cuprizone 12 weeks 5 weeks beam performance tests performed mice n 5 per group randomly divided five groups control c ms ms exercise ms + exe ms probiotic ms + prob ms probiotic exercise ms + prob + exe exercise groups performed aerobic exercises 5 days week 10 min first week 20 min second week 30 min daily third week eighth week probiotic groups mice received probiotic gavage sacrificed 3 months biochemical molecular biology analyses performedresults results showed leptin gene expression values ms + prob + exe ms + prob ms + exe groups showed decrease compared ms group reduction significant p 005 also leptin elisa test intervention groups showed significant decrease p 005 serotonin gene expression values ms + prob + exe ms + prob ms + exe groups increased compared ms group increase significant p 005 furthermore serotonin elisa test intervention groups showed significant increase p 005 cortisol elisa test values ms + exe ms + prob groups exhibited decrease compared ms group reduction significant p 005 conclusion overall results suggest lifestyle interventions can effective improving pathological factors patients mspmid34049259 doi101016 jcyto2021155590,1.0
validity reliability suggested immobilization test measurement restless legs syndrome severity adults multiple sclerosis sleep med 2021 jun 16 84343351 doi 101016 jsleep202106005 online ahead printabstractobjective background adults multiple sclerosis ms often present conditions mimic restless legs syndrome rls thereby adding complexity assessment rls severity current goldstandard measures rls severity rely fixed sevenday time frame limits ability measures studying acute changes rls severity present study examined subjective objective scores suggested immobilization test sit provide valid reliable acute measure rls severity persons mspatients methods participants ms rls n 20 ms without rls n 20 matched age gender disability participants completed validated questionnaires rls severity followed sit conducted 1800 15 min day week two consecutive weeks participants wore accelerometer devices seven nights capture periodic limb movements plms nightresults selfreported rls severity sit excellent construct validity convergent validity moderate testretest reliability devicemeasured plms direct measure rls severity significantly associated plms night excellent testretest reliability sit adults msconclusions results suggest sit represents valid acute measure capturing selfreported sensory aspects rls severity considered future research clinical practice standardized acute measure subjective rls severity adults ms present rlspmid34242924 doi101016 jsleep202106005,0.0
active elasticity drives formation periodic beading damaged axons phys rev e 2021 aug 104 21 024417 doi 101103 physreve104024417abstractin several pathological conditions coronavirus infections multiple sclerosis alzheimers parkinsons diseases physiological shape axons altered periodic sequence bulges appears experimental evidences suggest morphological changes caused disruption microtubules composing cytoskeleton axon paper develop mathematical model damaged axons based theory continuum mechanics nonlinear elasticity axon described cylinder composed inner passive part called axoplasm outer active cortex composed mainly factin able contract thanks myosinii motors linear stability analysis show shear modulus axoplasm diminishes due disruption cytoskeleton active contraction cortex makes cylindrical configuration unstable axisymmetric perturbations leading beading pattern finally nonlinear evolution bifurcated branches investigated finite element simulationspmid34525524 doi101103 physreve104024417,0.0
effect shoe cushioning gait balance females multiple sclerosis exp brain res 2021 jul 1 doi 101007 s00221021061611 online ahead printabstractgait balance deficits significant concerns people multiple sclerosis ms shoe cushioning can influence mobility balance effect walking balance remains unknown ms study aimed determine shoe cushioning affects gait balance females ms fwms hypothesized extra cushioning improve gait reduce balance performance fwms performed gait n 18 balance n 17 assessments instrumented using inertial sensors two different shoe conditions standardcushioned extracushioned shoe care taken ensure minimal differences shoe types midsole cushioning shoe construction identical conditions spatiotemporal gait parameters assessed 2min walk test postural sway measures evaluated using modified clinical test sensory interaction balance extracushioned shoe fwms spent less time double support stance phase time single support swing phase differences stride length gait speed elevation midswing observed shoe conditions decreased path length rms sway sway velocity observed extracushioned shoe differences observed gait cycles spatial composition shoe conditions fwms demonstrated improvements gait cycles temporal parameters postural sway extracushioned shoe may suggest less cautious walking strategy improved balance wearing shoe extra cushioningpmid34212220 doi101007 s00221021061611,0.0
electronic health record technology designed clinical encounter ms neuroshare neurol clin pract 2021 aug 11 4 318326 doi 101212 cpj0000000000000986abstractobjective advances medical discoveries bolstered expectations precise complete care delivering promise complex chronic neurologic care delivery requires solving lastmile challenges describe iterative humancentered design pilot process multiple sclerosis ms neuroshare digital health solution brings practical information point care clinicians patients ms can view discuss make informed decisions togethermethods initiated comprehensive humancentered process iteratively design develop implement digital health solution managing ms routine outpatient setting nonprofit sutter health system northern california humancentered codesign process included 3 phases discovery design development implementation pilot stakeholders included sutter healths research development dissemination team academic domain experts neurologists patients ms advisory groupresults ms neuroshare went live november 2018 included patient clinicianfacing web application launches electronic health record visually displays patients data relevant ms prompts clinician comprehensively evaluate treat patient patients clinicians valued ability jointly view patientgenerated data preliminary results suggest ms neuroshare promotes patientclinician communication active patient participation decisionmakingconclusions lessons learned design implementation ms neuroshare broadly applicable design implementation digital tools aiming improve experience delivering receiving highquality care complex neurologic conditions across large health systemspmid34484932 pmcpmc8382438 doi101212 cpj0000000000000986,0.0
pregnancyrelated perinatal outcomes women multiple sclerosis nationwide danish crosssectional study neurol clin pract 2021 aug 11 4 280290 doi 101212 cpj0000000000001035 epub 2021 feb 3abstractobjective investigate differences pregnancyrelated perinatal outcomes women multiple sclerosis ms compared general populationmethods conducted crosssectional study including pregnancies january 1 1997 december 31 2016 women registered danish multiple sclerosis registry study cohort pregnancyrelated perinatal outcomes compared randomly selected subcohort pregnancies general population comparison cohort using logistic regression adjusted possible confoundersresults total 2 930 pregnancies included study cohort 56 958 pregnancies comparison cohort differences found pregnancyrelated complications preeclampsia gestational diabetes placenta complications emergency caesarean section csection instrumental delivery low apgar score stillbirth preterm birth congenital malformations elective csection odds ratio 189 95 confidence interval ci 165216 induced delivery 115 95 ci 101131 born small gestational age sga 129 95 ci 104160 higher prevalence study cohort whereas prevalence signs indicating asphyxia lower study cohort 087 95 ci 078097 relative comparison cohortconclusion found higher prevalence elective csections induced delivery infants sga among newborns women ms whereas prevalence asphyxia lower study cohort significant differences severe adverse perinatal outcomes comparing women ms newborns general populationpmid34484927 pmcpmc8382416 doi101212 cpj0000000000001035,0.0
classification criteria pars planitis j ophthalmol 2021 apr 9s00029394 21 001707 doi 101016 jajo202103045 online ahead printabstractpurpose determine classification criteria pars planitis design machine learning cases pars planitis 4 intermediate uveitidesmethods cases intermediate uveitides collected informaticsdesigned preliminary database final database constructed cases achieving supermajority agreement diagnosis using formal consensus techniques cases split training set validation set machine learning using multinomial logistic regression used training set determine parsimonious set criteria minimized misclassification rate among intermediate uveitides resulting criteria evaluated validation setresults five hundred eightynine cases intermediate uveitides including 226 cases pars planitis evaluated machine learning overall accuracy intermediate uveitides 998 training set 993 validation set 95 confidence interval 961 999 key criteria pars planitis included unilateral bilateral intermediate uveitis either 1 snowballs vitreous 2 snowbanks pars plana key exclusions included 1 multiple sclerosis 2 sarcoidosis 3 syphilis misclassification rates pars planitis 0 training set 17 validation set respectivelyconclusions criteria pars planitis low misclassification rate appeared perform sufficiently well use clinical translational researchpmid33845006 doi101016 jajo202103045,0.0
change #39 firsttrial#39 performance protective step practice people multiple sclerosis clin biomech bristol avon 2021 aug 13 88105448 doi 101016 jclinbiomech2021105448 online ahead printabstractbackground multiple sclerosis ms debilitating neurodegenerative disorder causing considerable gait balance dysfunction reactive balance ie quick movements response loss balance particularly important fall risk impaired people ms compared neurotypical peers therefore improving reactive balance among ms critical however maximum ecological validity improvements reactive balance training demonstrable upon first lossofbalance rather average several trials typically reported study evaluated changes performance first stepping trial people ms one day practicemethods fourteen people ms underwent two consecutive days supportsurface perturbations stance day 1 participants underwent single backwardstepping trial followed 35 practice trails forward backward approximately 24 h later participants exposed single backward stepping perturbation protective stepping outcomes step length step latency margin stability first foot contact backward step performance first trial days one two compared difference scores evaluated relationships correlates based theoretical considerationsfindings firsttrial margin stability increased improved day 1 day 2 p 016 steps also faster average approximately 5 ms day 2 although improvement significant p 062 interpretations although preliminary findings provide evidence individuals ms may able experience firsttrial improvements low dose perturbation trainingpmid34418821 doi101016 jclinbiomech2021105448,1.0
perceived injustice multiple sclerosis initial exploratory study rehabil psychol 2021 aug 66 3 335343 doi 101037 rep0000387abstractpurpose objective current study represents initial examination conditionrelated perceived injustice pi multiple sclerosis ms examining structural validity reliability injustice experience questionnaire ieq scores b associations ieq scores scores measures anger pain depression anxiety fatigue disability healthrelated quality life hrqol physical activity sedentary behavior research method design persons ms recruited distribution letters random sample 1 000 persons north american research committee ms registry participants completed ieq n 139 included analysisresults results support structural validity 2factor model severity irreparability blame unfairness subscales cronbachs alpha 917 overall scale values 857 889 subscales respectively measures meaningfully correlated ieq scores pain 466 fatigue 430 disability 416 walking impairment 446 physical hrqol 624 strongly correlated severity irreparability anger however strongly correlated blame unfairness 437 physical activity sedentary behavior similarly correlated 2 subscales however moderatetovigorous 332 light physical activity 275 slightly correlated severity irreparabilityconclusions implications ieq reliable valid measure pi ms physical manifestations ms primarily associated pi negative associations observed physical activity ieq scores physical activity may increase selfefficacy counteract cognitions permanent disability frustration concerning limitations associated pi psycinfo database record c 2021 apa rights reserved pmid34472930 doi101037 rep0000387,0.0
2aminoethyl diphenylborinate inhibits bleomycininduced skin pulmonary fibrosis via interrupting intracellular ca2+ regulation j dermatol sci 2021 jul 13s09231811 21 001717 doi 101016 jjdermsci202107005 online ahead printabstractbackground systemic sclerosis ssc causes progressive fibrosis multiple organs low efficacy immunosuppressive therapies previous study indicated ssc pathological pathways closely correlated ca2+ signals blockage intracellular ca2+ elevation facilitates inhibition ssc pathogenesisobjective transforming growth factor tgf modulated smad signaling crucial regulating ssc pathogenesis whether ca2+ signals involved tgf1 smad signalinginduced fibrotic process investigatedmethods utilized tgf1induced myofibroblasts model detect ca2+ signals affected ssc pathogenesis investigated combination treatment storeoperated ca2+ entry soce associated inhibitors 2aminoethyl diphenylborinate 2apb skf96365 restrain increased ca2+ signaling myofibroblasts addition ssc bleomycin mouse model used detect effect 2apb ssc pathogenesis vivoresults findings revealed increased levels tgf1 production ssc associated intracellular ca2+ activity inhibition intracellular ca2+ regulation 2apb resulted dedifferentiation tgf1induced myofibroblasts due fact 2apb restrained expression fibrotic markers sma fibronectin vimentin inhibiting tgf1 smad3 signaling thus subcutaneous injection 2apb improved bleomycininduced skin pulmonary fibrosisconclusion 2apb potential candidate treating fibrosis disrupting intracellular ca2+ regulation ssc induce dedifferentiation myofibroblasts meliorates fibrosis pathogenesis via inhibiting tgf1 smad3 signalingpmid34315630 doi101016 jjdermsci202107005,0.0
impaired awareness people multiple sclerosis continue using cannabis despite evidence contrary brain behav 2021 jun 4 doi 101002 brb32220 online ahead printabstractbackground widespread moves toward legalization cannabis increasing numbers people multiple sclerosis pwms using drug emerging msrelated data show cannabis can cause exacerbate cognitive dysfunctionobjective understand people ms continue using cannabis despite adverse cognitive consequences hypothesized lack awareness component metacognition explain decision partmethod forty pwms smoked cannabis almost daily assigned oddeven case number selection either cannabis continuation cc cannabis withdrawal cw group groups followed 28 days participants completed baseline day 28 brief repeatable battery neuropsychological tests brnb ms measures processing speed memory executive function modified fatigue impact scale mfis selfreport indices cognitive functioningresults significant baseline differences groups brnb mfis day 28 significant improvement within group seen measures brnb cw group p 0001 indices repeat measure anova find significant group cc vs cw time baseline day 28 interactions selfreport cognitive measures mfis cannabis abstainers report less ability function away home 19 participants cw group reverted using cannabis study completion despite informed individually cognitive improvementconclusions relevance inability pwms accurately appraise memory executive function can help explain part continue smoke cannabis despite objective evidence deleterious cognitive side effects behaviorpmid34087949 doi101002 brb32220,0.0
comparative analysis modified rankin scale karnofsky performance status kurtzke expanded disability status scale perioperative management patients brainstem cavernous malformations clin neurol neurosurg 2021 jun 25 207106785 doi 101016 jclineuro2021106785 online ahead printabstractbackground neurological conditions brainstem cerebral cavernous malformation bcm patients usually ascertained using karnofsky performance status kps modified rankin scale mrs however scales reflect slight changes brainstem function neither kps mrs includes brainstem symptoms worsening swallowing diplopia main problem managing bcm patients can neither systematically record neurological changes conduct clinical outcome investigations bcm due lack adequately detailed assessment systempurpose investigated usefulness kurtzke expanded disability status scale edss already widespread clinical use multiple sclerosis provides certainty evaluating brainstem symptomsmethods retrospectively analyzed neurological transitions surgical bcm cases using modified rankin scale mrs karnofsky performance status kps edss compared neurological score transition determined scale allows accurate recording neurological changes patientsresults proposed lesion removal patients showed neurological deterioration lesion enlargement caused rebleeding surgery accepted 10 patients edss allowed us assess patient status accurately kps mrs particularly perioperative period statistical analysis edss differed significantly period initial proposal surgery immediate preoperative periodconclusion results suggest edss superior managing bcm patients compared kps mrs thus edss may serve alternative scale assessing bcm patientspmid34252689 doi101016 jclineuro2021106785,0.0
significant immunomodulatory hepatoprotective impacts silymarin ms patients doubleblind placebocontrolled clinicaltrial int immunopharmacol 2021 apr 29 97107715 doi 101016 jintimp2021107715 online ahead printabstractinterferon beta ifn successfully experimented treat multiple sclerosis ms however patients sometimes respond effectively treatment adverse effects including liver toxicity accompany therapy accordingly decided treat ms patients simultaneously silymarin sm immunomodulatory hepatoprotective agent ifn clinical trial study complete blood count cbc liver enzyme levels serum concentration inflammatory antiinflammatory cytokines measured also frequency immune cells determined flow cytometry liver enzyme levels significantly lower intervention group p 005 percentage th17 cells intervention group significantly reduced compared placebo group p 0001 also frequency treg cells treatment sm plus ifn significantly increased compared placebo group p 005 furthermore il17 ifn cytokine levels significantly reduced intervention group p 005 moreover levels antiinflammatory cytokines il10 tgf significantly increased intervention group p 005 overall results provide novel supplementary information sms notable immunoregulatory effects inflammatory response liver function ms patients clinical trial identifier number irctid irct20171220037977n1pmid33933848 doi101016 jintimp2021107715,0.0
effect optic neuritis attacks choroidal vascularity index patients multiple sclerosis graefes arch clin exp ophthalmol 2021 mar 25 doi 101007 s0041702105143x online ahead printabstractpurpose investigate changes choroidal vascularity index cvi patients multiple sclerosis ms using binarization enhanced depth imaging optical coherence tomography edioct images evaluate effect optic neuritis attacks measurementsmethod three groups created including forty eyes 20 patients diagnosed relapsingremitting ms unilateral history attack randomly selected eyes 30 healthy age sexmatched control subjects group 1 n 20 consisted onaffected eyes ms patients mson group 2 n 20 included fellow healthy eyes msnon group 3 n 30 included eyes healthy controlsresults mean age 333 94 years ms group 334 111 years healthy control group mean choroidal vascularity index cvi significantly lower mson group msnon group 596 372 vs 617 316 p 0007 cvi values mson msnon groups significantly lower compared controls 639 276 p 0001 p 0030 compared controls subfoveal total choroidal area luminal area values significantly greater mson p 0009 p 0009 respectively msnon groups p 0031 p 0013 respectively conclusion presented study demonstrates compared healthy subjects cvi values lower affected unaffected eyes patients history relation ms diagnosis presence significant anatomical changes especially luminal area may suggest causes vascular disorganization contributes ms pathophysiologypmid33763732 doi101007 s0041702105143x,0.0
longitudinal change tspo pet imaging progressive multiple sclerosis ann clin transl neurol 2021 jul 26 doi 101002 acn351431 online ahead printabstractthe objective pilot study assess 2year change innate immune burden 15 progressive multiple sclerosis ms patients using pk11195pet sixteen agematched healthy controls hc included baseline comparison pk11195 uptake higher ms patients compared hc within normalappearing white matter nawm multiple gray matter regions patients pk11195 uptake increased nawm p 001 cortex p 004 thalamus p 004 putamen p 002 12 months among patients remaining 24 months increase pk11195 data suggest innate immune activity may increase time patients progressive mspmid34310086 doi101002 acn351431,0.0
overview stem cells therapy amyotrophic lateral sclerosis neurol res 2021 feb 25117 doi 101080 0161641220211893564 online ahead printabstractbackground amyotrophic lateral sclerosis als progressive neurodegenerative disease upper lower motor neurons high burden society despite tremendous efforts last several decades still definite cure als now two diseasemodifying agents riluzole edaravone approved us food drug administration fda als treatment modestly improves survival disease progression major challenging issues find effective therapy heterogeneity pathogenesis genetic variability als stem cell therapy recently focus preclinical clinical investigations als stem cells multifaceted features can potentially target multiple pathogenic mechanisms als even though underlying mechanisms completely elucidated methods results will overview stem cell therapy als including therapeutic mechanisms results recent clinical trials well ongoing clinical trials addition will discuss complications limitations stem cell therapy als conclusion determination whether stem cells offer viable treatment strategy als rests welldesigned appropriately powered future clinical trials randomized doubleblinded shamcontrolled studies valuablepmid33632084 doi101080 0161641220211893564,0.0
neuroprotective effects telmisartan nifedipine cuprizoneinduced demyelination behavioral dysfunction mice roles nfb nrf2 inflammation 2021 mar 11 doi 101007 s10753021014476 online ahead printabstractmultiple sclerosis chronic inflammatory neurodegenerative disease central nervous system injures myelin sheath telmisartan nifedipine antihypertensive drugs recently showed neuroprotective properties neurodegenerative diseases study evaluated neuroprotective effect telmisartan nifedipine cuprizoneinduced demyelination mice examining underlying mechanisms c57bl 6 mice received diet containing 07 w w cuprizone 7 days followed 3 weeks 02 cuprizone diet telmisartan 5 mg kg day po nifedipine 5 mg kg day po administered 3 weeks starting second week telmisartan nifedipine improved locomotor activity enhanced motor coordination demonstrated open field rotarod grip strength tests furthermore telmisartan nifedipine restored myelin basic protein mrna protein expression increased luxol fast bluestaining intensity telmisartan nifedipine attenuated cuprizoneinduced oxidative stress apoptosis decreasing brain malondialdehyde caspase3 along restoring reduced glutathione brainderived neurotrophic factor levels telmisartan nifedipine exerted antiinflammatory effect reducing expression nuclear factor kappa b nfb p65 well proinflammatory cytokines elevating expression ib parallel telmisartan nifedipine upregulated expression nuclear factor erythroid 2related factor 2 nrf2 levels heme oxygenase1 nadph quinone oxidoreductase 1 enzymes conclusion current study provides evidence protective effect telmisartan nifedipine cuprizoneinduced demyelination behavioral dysfunction mice possibly modulating nfb nrf2 signaling pathwayspmid33709265 doi101007 s10753021014476,1.0
modifying diet exercise ms modems study design protocol telehealth weight loss intervention adults obesity amp multiple sclerosis contemp clin trials 2021 jun 30106495 doi 101016 jcct2021106495 online ahead printabstractweight loss improves overall health reduces inflammation risk stroke heart attack diabetes certain cancers death among individuals obesity weight loss also improves mobility increases stamina elevates mood 25 33 people multiple sclerosis pwms obesity multiple sclerosis ms obesity independently associated reduced mobility increased fatigue depression behavioral weight loss trials exclude individuals neurologic disease consequently studies examined effects weight loss symptom presentation health outcomes among pwms obesity first study examining efficacy comprehensive behavioral weight loss intervention designed specifically pwms purpose study develop assess efficacy telehealth administered weight loss intervention tailored pwms additionally aim determine weight loss reduces physical emotional symptoms individuals obesity ms will enroll 70 pwms waitlist crossover trial examine efficacy intervention successful findings will help determine whether can help participants lose clinically significant weight whether weight loss among pwms overweight obesity reduces fatigue improves mobility mood quality lifepmid34216814 doi101016 jcct2021106495,1.0
world brain day 2021 global campaign stop multiple sclerosis mult scler 2021 jul 1413524585211030147 doi 101177 13524585211030147 online ahead printno abstractpmid34256624 doi101177 13524585211030147,0.0
prevalence covid19 infection patients multiple sclerosis ms systematic review metaanalysis neurol sci 2021 jun 7 doi 101007 s10072021053731 online ahead printabstractbackground prevalence covid19 different studies conducted different countries aim systematic review metaanalysis estimate pooled prevalence covid19 patients msmethods two independent researchers independently searched pubmed scopus embase web science google scholar along gray literature april 2021 search strategy included mesh text words coronavirus wuhan coronavirus novel coronavirus coronavirus disease covid19 2019 novel coronavirus infection 2019ncov severe acute respiratory syndrome coronavirus 2 sarscov2 multiple sclerosis sclerosis multiple sclerosis disseminated disseminated sclerosis ms multiple sclerosis multiple sclerosis acute fulminating results found 1466 articles literature search deleting duplicates 1029 remained twelve articles remained metaanalysis totally 101 462 patients evaluated total number possible confirmed cases 1394 mean age ranged 35 54 years totally 49 patients died pooled prevalence suspected covid19 ms patients 4 95 ci 34 i2 985 p 0001 pooled prevalence hospitalization infected cases 10 95 ci 712 i2 956 p 0001 pooled prevalence death hospitalized cases 4 95 ci 16 i2 824 p 0001 conclusion hospitalization rate higher among ms patients based covid19 infection pooled infection rate estimated 4pmid34100130 doi101007 s10072021053731,1.0
fty720 exacerbates bloodbrain barrier dysfunction induced igg derived patients nmo mog disease neurotox res 2021 may 17 doi 101007 s12640021003737 online ahead printabstractneuromyelitis optica nmo myelin oligodendrocyte glycoprotein mog antibodyrelated disease mog disease inflammatory demyelinating diseases central nervous system cns disruption bloodbrain barrier bbb considered key step pathogenesis nmo mog disease although previous report indicated circulating immunoglobulin g igg nmo patients disrupts bbb effect igg patients mog disease elucidated addition reported diseasemodifying drugs multiple sclerosis harmful nmo unknown mechanism study aimed examine effects igg patients nmo mog disease bbb integrity also examined effects diseasemodifying drugs fingolimod fty720 dimethyl fumarate dmf iggtreated brain capillary endothelial cells used vitro bbb models constructed rat brain capillary endothelial cells rbecs examine effects bbb function integrity rbecs assessed measuring transendothelial resistance teer cell viability nmo mogigg treatment decreased teer cell viability endothelial monolayer model although fty720 dmf affect barrier function cell viability normal conditions disease igginduced barrier dysfunctions worsened presence fty720 data indicate circulating igg patients nmo mog disease worsens bbb function furthermore patients nmo mog disease treated fty720 changes integrity bbb found exacerbate diseasepmid33999356 doi101007 s12640021003737,1.0
wireless subcutaneous trigeminal nerve field stimulation refractory trigeminal pain single center experience neuromodulation 2021 jul 27 doi 101111 ner13478 online ahead printabstractintroduction subcutaneous trigeminal nerve field stimulation stnfs neuromodulatory treatment neuropathic trigeminal pain ability reduce intensity frequency pain attacks however hardware issues including lead migration skin erosion infection socalled pocket pain site implanted neurostimulator reported implantable wireless neurostimulation technology promises even less invasive stnfs treatment thinner flexible electrodes better suited facial implants also provides advantages lack implantable neurostimulator 3t magnetic resonance imaging compatibilitymaterial methods patients received trial stimulation partially implantable stnfs system analyzed ichd3 3rd edition international classification headache disorders diagnosis success trial stimulation pre postoperative pain intensity frequency attacks complications sideeffects stnfsresults patients n 3 responded stnfs 50 pain reduction trial period according ichd3 n 2 patients classified trigeminal neuralgia tn concomitant persistent facial pain n 1 patient multiple sclerosis associated tn time test period 44 3124 days mean sd average daily duration stimulation per patient amounted 25 22 hours range 15 pain intensity defined visual analog scale reduced 80 17 mean sd reduction cessation pain medication observed patients surgical complications occurred longterm followup period 1884 6 mean sd monthsconclusion partially implantable stnfs device seems safe effective reliable compared conventional devices equipment limited length trial stimulation furthermore daily stimulation duration much shorter compared previous reportspmid34313358 doi101111 ner13478,0.0
diseasemodifying therapies relapsingremitting multiple sclerosis liver injury narrative review cns drugs 2021 jul 28 doi 101007 s40263021008429 online ahead printabstractin narrative review analyze preregistration postmarketing data concerning hepatotoxicity diseasemodifying therapies dmts available treatment relapsingremitting multiple sclerosis including beta interferon glatiramer acetate fingolimod teriflunomide dimethyl fumarate cladribine natalizumab alemtuzumab ocrelizumab review proposed causal mechanisms described literature also address issues like use dmts patients viral hepatitis liver cirrhosis data emerged postmarketing phase reports national pharmacovigilance agencies published case reports case series serious liver adverse events rare exact incidence largely unknown predictive factors unfortunately none dmts currently available treatment multiple sclerosis free potential hepatic toxic effects cases acute liver failure reported betainterferon fingolimod natalizumab alemtuzumab ocrelizumab different mechanisms idiosyncratic reaction autoimmune hepatitis viral reactivation patients multiple sclerosis informed possible hepatic side effects treatment cases liver injury idiosyncratic unpredictable specific monitoring schedule dmt reviewed clinician ready recognize clinical symptoms suggestive liver injury dmts indicated cirrhotic patients dmts screening hepatitis b virus hepatitis c virus required starting treatment monitoring antiviral prophylaxis schedule established beta interferon glatiramer acetate natalizumab alemtuzumab relatively contraindicated autoimmune hepatitis due risk disease exacerbationpmid34319570 doi101007 s40263021008429,0.0
lateonset multiple sclerosis initially presenting acute psychiatric symptomatology case report ann clin psychiatry 2021 aug 33 3 208209 doi 1012788 acp0038no abstractpmid34398736 doi1012788 acp0038,0.0
trimethylamine noxide gut microbiotaderived metabolite associated cardiovascular risk psoriasis crosssectional pilot study dermatol ther heidelb 2021 may 13 doi 101007 s13555021005473 online ahead printabstractintroduction trimethylamine noxide tmao gut microbiota metabolite dietary phosphatidylcholine involved pathogenesis atherosclerosis cardiovascular diseases psoriasis associated increased cardiovascular risk captured traditional biomarkers aim present study assess tmao concentration psoriasis evaluate relationship tmao cardiovascular risk psoriatic patientsmethods 72 patients psoriasis 40 age sexmatched nonpsoriatic controls evaluated fasting plasma tmao measured highperformance liquid chromatography cardiovascular risk assessed various scoring systems framingham qrisk2 aha acc reynolds risk scoresresults patients psoriasis tmao concentration significantly higher control group 19568 1335433258 ng ml versus 12606 842915688 ng ml respectively p 0001 plasma tmao concentration significantly correlated age total cholesterol triglycerides systolic diastolic blood pressure furthermore receiveroperating characteristic roc multiple regression analysis showed tmao independent predictor cardiovascular riskconclusion tmao valuable candidate biomarker translational link dysbiosis atherosclerosis psoriasispmid33983475 doi101007 s13555021005473,0.0
prediction unenhanced lesion evolution multiple sclerosis using radiomicsbased models machine learning approach mult scler relat disord 2021 may 4 53102989 doi 101016 jmsard2021102989 online ahead printabstractbackground volume change multiple sclerosis ms lesion related activity can used assess disease progression therefore purpose study develop radiomics models predicting evolution unenhanced ms lesions using different kinds machine learning algorithms explore optimal modelmethods prospective observation 45 followup mr images obtained 36 patients ms mean age 32531091 23 women 13 men evaluated lesions will defined interval activity interval inactivity respectively based percentage enlargement reduction lesion 20 followup mr images extracted radiomic features lesions flair images used recursive feature elimination rfe relieff algorithm least absolute shrinkage selection operator lasso feature selection three classification models including logistic regression random forest support vector machine svm used build predictive models performance models evaluated based sensitivity specificity precision negative predictive value npv receiver operating characteristic curve roc curves analysesresults 135 interval inactivity lesions 110 interval activity lesions registered study total 972 radiomics features extracted 265 robust consistency effectiveness model performance compared verified different combinations feature selection machine learning methods different kfold crossvalidation strategies k ranges 5 10 thus demonstrating stability robustness svm classifier relieff algorithm best prediction performance average accuracy 0827 sensitivity 0809 specificity 0841 precision 0921 npv 0948 areas roc curves auc 0857 95 ci 08120902 cohortsconclusion results demonstrated radiomicsbased machine learning model potential predicting evolution ms lesionspmid34052741 doi101016 jmsard2021102989,0.0
retention antiseizure medications epilepsy multiple sclerosis retrospective observational study epilepsy behav 2021 may 15 121 pt 108034 doi 101016 jyebeh2021108034 online ahead printabstractpurpose epilepsy multiple sclerosis ms rare longitudinal clinical studies evaluating treatment antiseizure medications asms difficult conduct instead designed nationwide register study estimate retention rates asms prescribed initial monotherapy epilepsy ms investigated factors influencing retentionmethods multiple sclerosis patients first prescription asm epilepsy identified crossreferencing swedish ms register comprehensive national registers one fiveyear retention rates asms estimated using kaplanmeier analysis cox proportional regression employed estimate hazard ratios hr discontinuation different asms well baseline predictorsresults one hundred twentynine ms patients included commonly prescribed asms carbamazepine n 38 295 lamotrigine n 33 256 levetiracetam n 19 147 oneyear retention rates 95 ci lamotrigine 875 76 989 carbamazepine 605 45 76 levetiracetam 602 372 832 valproate 513 23 796 phenytoin 444 118 77 fiveyear retention rates 95 ci lamotrigine 744 573 915 carbamazepine 522 349 694 valproate 513 231 795 phenytoin 148 0 409 carbamazepine reference lamotrigine asm displayed lower hazard discontinuation hr 041 017 099 identify baseline factors influenced risk discontinuationconclusion lamotrigine displayed lowest risk discontinuation prescribed initial monotherapy epilepsy ms newer asms generally compared well older ones least suggesting noninferioritypmid34004524 doi101016 jyebeh2021108034,0.0
development validation vanderbilt fatigue scale adults vfsa psychol assess 2021 apr 15 doi 101037 pas0001021 online ahead printabstractlisteningrelated fatigue can significant burden adults hearing loss ahl potentially health languagerelated issues eg multiple sclerosis traumatic brain injury second language learners must allocate substantial cognitive resources process listening 40item vanderbilt fatigue scale adults vfsa40 designed measure listeningrelated fatigue populations article describes development psychometric properties vfsa40 initial qualitative analyses ahl suggested listeningrelated fatigue multidimensional physical mental emotional social domains however exploratory factor analyses revealed unidimensional structure item test characteristics evaluated using item response theory irt results confirmed test items high quality irt analyses revealed high marginal reliability analysis testretest scores revealed adequate reliability addition analysis differential item functioning provided evidence good construct validity across age gender hearing loss groups sum vfsa40 reliable valid tool quantifying listeningrelated fatigue adults believe vfsa40 will useful identifying risk severe listeningrelated fatigue assessing interventions reduce negative effects psycinfo database record c 2021 apa rights reserved pmid33856826 doi101037 pas0001021,0.0
magnetic resonance characteristics balo concentric sclerosis children pediatr neurol 2021 may 19 121310 doi 101016 jpediatrneurol202105008 online ahead printabstractbackground bal concentric sclerosis rare demyelinating disease characteristic magnetic resonance appearance multilayered ringlike lesions demyelination disease extremely rare children present clinical data radiological appearance development lesions eight childrenmethods analyzed clinical information eight patients diagnosed 2012 2020 magnetic resonance brain spinal cord examinations contrast medium administration performed using 15t scannerresults patients presented least one typical bal lesion brain imaging four patients additionally typical multiple sclerosis plaques primary bal lesions characteristic appearance concentric hyperintense rings t2weighted imaging round ovoid cerebrospinal fluid analysis performed patients oligoclonal bands present seven patients four multiple sclerosis plaques baseline brain magnetic resonance imagingconclusion bal concentric sclerosis children characterized acute severe onset hemiparesis predominant symptom size contrast enhancement restricted diffusion changed depending phase diseasepmid34111620 doi101016 jpediatrneurol202105008,1.0
risk thromboembolic events associated risk factors including treatments patients immunemediated diseases clin ther 2021 jul 6s01492918 21 002393 doi 101016 jclinthera202106008 online ahead printabstractpurpose study assessed association thromboembolic events tes immunemediated diseases imds characterized risk profile tes among patients imdsmethods administrative claims database 20142018 used identify adults 2 diagnoses different dates 1 imd imd cohort ankylosing spondylitis atopic dermatitis inflammatory bowel disease multiple sclerosis psoriasis psoriatic arthritis rheumatoid arthritis systemic lupus erythematosus patients without imd diagnosis assigned nonimd cohort patients imd cohort matched 11 patients nonimd cohort age sex index date incremental risk te ie deep vein thrombosis dvt pulmonary embolism pe myocardial infarction mi ischemic stroke assessed using adjusted incidence rate ratios airrs control covariates cohorts risk factors tes assessed imd cohort included age female sex comorbidities baseline tes nonimd treatments imd treatmentsfindings total 182 431 patients included cohort mean age 513 years 643 female higher proportion patients imd cohort versus nonimd cohort 1 baseline te 41 vs 27 p 00001 imd cohort 180 95 ci 168192 p 00001 times higher rate tes versus patients nonimd cohort adjustments patients imd cohort 149 95 ci 140159 p 00001 times higher rate tes versus patients nonimd cohort similar results observed across individual tes dvt airr 178 pe airr 166 mi airr 117 airr 135 p 005 risk factor profiles varied te greatest risk factor respective te baseline eg patients baseline dvt 411 times rate dvt study period vs patients without baseline dvt p 0001 comorbidities cardiovascular diseases type 2 diabetes peripheral vascular disease associated increased rates mi irr 260 130 154 respectively p 005 irr 153 154 124 respectively p 005 janus kinase inhibitors associated increased rate pe irr 252 p 005 nonsignificant numerically higher rates dvt irr 123 p ns irr 182 p ns sphingosine 1phosphate receptor modulators associated decreased rates tes dvt irr 061 p ns pe irr 030 p ns mi irr 054 p ns irr 033 p 005 implications risk tes higher among patients imd versus patients without imd several factors may affect riskpmid34238587 doi101016 jclinthera202106008,0.0
association study promoter polymorphisms interferon alpha beta receptor subunit 1 ifnar1 gene therapeutic response interferonbeta patients multiple sclerosis mol biol rep 2021 jul 30 doi 101007 s11033021066028 online ahead printabstractbackground multiple sclerosis ms autoimmune disease described inflammatory neuronal losses resultant failures disease abate interferonbeta ifn therapy ms patients however drug response productivity changeable patients accurate mechanism action ifn obvious present study aims investigate role interferon alpha beta receptor subunit 1 ifnar1 promoter polymorphisms towards ifn treatment response ms patientsmethods subjects herein separated either responder n 57 nonresponder n 43 groups according ifn treatment expanded disability status scale score sanger sequencing method used genotypingresults among nearly 64 single nucleotide polymorphisms snps found significant association rs2850015 polymorphism responders nonresponders ifn treatment recessive model inheritance p 002 results also revealed significant change two groups responders nonresponders treatment rs36158718 insertion deletion indel p 002 moreover bioinformatic analyses predicted remarkable role rs2850015 rs36158718 related changes binding affinity transcription factors alterations allelesconclusion present study results suggest genetic heterogeneity promoter region ifnar1 affect response ifn however studies larger sample size needed demonstrate relationshippmid34328599 doi101007 s11033021066028,0.0
familybased exome sequencing identifies rbm45 possible candidate gene frontotemporal dementia amyotrophic lateral sclerosis neurobiol dis 2021 jun 9105421 doi 101016 jnbd2021105421 online ahead printabstractneurodegenerative disorders like frontotemporal dementia ftd amyotrophic lateral sclerosis als pathologically characterized toxic protein deposition cytoplasm nucleus affected neurons glial cells many aggregated proteins belong class rna binding proteins rbp mutated account significant subset familial als ftd cases present first genetic evidence rbp gene rbm45 ftdals spectrum rbm45 shows many parallels ftdals associated genes proteins multiple lines evidence demonstrated rbm45 rbp upon mutation redistributes cytoplasm coaggregates rbps cytoplasmic stress granules sg evolving persistent toxic tdp43 immunoreactive inclusions exome sequencing two affected first cousins heavily affected earlyonset dementia family listed number candidate genes gene highest pathogenicity score rbp gene rbm45 family rbm45 arg183 nonsense mutation cosegregated affected cousins validation unrelated patient n 548 control n 734 cohort identified additional rbm45 arg183 carrier bvftd shared 4 mb haplotype transcript protein expression analysis demonstrated loss nuclear rbm45 suggestive lossoffunction disease mechanism two ultrarare vus one nuclear localization signal nls plys456arg als patient one intrinsically disordered homooligomer assembly hoa domain parg314gln patient nfvppa detected findings suggest pathomechanisms linking rbm45 ftd als may related loss nuclear function mediator mrna splicing cytoplasmic retention inability form homooligomers leading aggregate formation trapping rbps including tdp43 may accumulate persisted tdp43 inclusionspmid34118419 doi101016 jnbd2021105421,0.0
early diagnosis newborn tuberous sclerosis caused genetic mutation j int med res 2021 aug 49 8 3000605211035895 doi 101177 03000605211035895abstractobjective tuberous sclerosis tsc autosomal dominant disorder often detected childhood present results genetic testing newborn suspected tscmethods newborn specific clinical manifestations tsc showed evidence tsc magnetic resonance imaging echocardiography nextgeneration sequencing ngs multiple ligationdependent probe amplification mlpa tsc1 tsc2 gene exons carried confirm diagnosisresults results mlpa negative ngs showed heterozygous mutation tsc1 gene comprising insertion t residue c2165 exon 17 c2166 exon 17 indicating loss function mutation results verified sanger sequencing genetic change present newborn parental genotypes wildtype indicating de novo mutationconclusions case case tsc caused heterozygous mutation tsc1 gene confirmed ngs sequencing indicates suitability genetic testing early diagnosis clinically rare difficulttodiagnose diseases guide clinical treatmentpmid34433328 doi101177 03000605211035895,0.0
radiologically isolated syndrome antiquated amidst evolving mcdonald criteria multiple sclerosis erratum cns spectr 2021 aug 26 4 436 doi 101017 s1092852920001790no abstractpmid34332649 doi101017 s1092852920001790,0.0
consensus curriculum fellowship training multiple sclerosis neuroimmunology neurol clin pract 2021 aug 11 4 352357 doi 101212 cpj0000000000001040abstractmanagement multiple sclerosis neuroimmunologic disorders become increasingly complex expanding number recognized neuroimmune disorders increased number therapeutic options multidisciplinary care management needs people multiple sclerosis neuroimmunologic disorders subspecialists needed optimize care patients many fellowship programs created expanded increase subspecialty workforce consequently defining scope standardizing fellowship training essential ensure trainees receive highquality training workgroup created develop consensus fellowship curriculum serve resource current future training programs curriculum may also serve basis future accreditation effortspmid34484933 pmcpmc8382436 doi101212 cpj0000000000001040,0.0
risk assessment obstructive sleep apnea syndrome sleep disorders multiple sclerosis patients clin neurol neurosurg 2021 jun 8 207106749 doi 101016 jclineuro2021106749 online ahead printabstractbackground aim present study determine possible risk osas patients ms stopbang questionnaire confirm prediagnosis osas recording polysomnographic investigation individuals high risk addition relationship osas risk fatigue sleepiness depression disability status will examinedmethods totally 97 patients multiple sclerosis including 36 males 61 females age average 3992 911 years participants completed following questionnaires stopbang fatigue severity scale fss epworth sleepiness scale ess beck depression inventory bdi disability status participants assessed expanded disability status scale edss polysomnographic sleep record applied patients high risk osas according stopbang test scoresresults stop_bang questionnaire revealed 247 patients screened high risk osa approximately 113 patients detected positive osas based psg recording comparison ms patients high risk osa others suggested significant difference terms age p 001 ess positive scores significantly correlated positive stop bang outcomes p 0001 ess positive scores negatively correlated positive psg outcomesconclusion prevalence osas ms patients based questionnaire psg found consistent literature similar general population increasing age found risk factor osas patients ms stopbang test may adequate test diagnose osas especially ms patients high fatigue scorespmid34126453 doi101016 jclineuro2021106749,0.0
upper extremity motor fatigability early indicator pediatric onset multiple sclerosis j child neurol 2021 mar 19883073821999889 doi 101177 0883073821999889 online ahead printabstractaim adopt computerbased protocol assess grip fatigability patients pediatriconset multiple sclerosis provide detection subtle motor involvement identifying patients risk future declinemethod pediatriconset multiple sclerosis patients recruited routine outpatient visits complete grip assessment compared group healthy age sexmatched controls participants completed computerbased measurement standard maximal grip strength repetitive sustained grip performance measured dynamic static fatigue indicesresults total 38 patients pediatriconset multiple sclerosis 24 healthy controls completed grip protocol righthand dominant significant group differences maximal grip strength bilaterally right 218 vs 199 kg p 25 left 204 vs 187 kg p 33 although males pediatriconset multiple sclerosis significantly less strong healthy controls right 2653 vs 2123 kg p 009 left 2513 vs 1963 kg p 003 dynamic static fatigue indices significantly higher bilaterally pediatriconset multiple sclerosis compared healthy control participants lefthand dynamic fatigue index 186 vs 267 p 003 righthand static fatigue index 283 vs 413 p 001 lefthand static fatigue index 319 vs 426 p 001 conclusion brief repeatable grip assessment including measures dynamic sustained static output can sensitive indicator upper extremity motor involvement pediatriconset multiple sclerosis potentially identifying need intervention prevent future disabilitypmid33736529 doi101177 0883073821999889,0.0
safety immunological proofofconcept following treatment toleranceinducing cell products patients autoimmune diseases receiving organ transplantation systematic review metaanalysis clinical trials autoimmun rev 2021 jun 10102873 doi 101016 jautrev2021102873 online ahead printabstractin past years translational approaches led earlystage clinical trials assessing safety efficacy toleranceinducing cellbased treatments patients review aims determine toleranceinducing cellbased therapies including dendritic cells regulatory t cells mesenchymal stem cells safe adult patients underwent organ transplantation autoimmune diseases including multiple sclerosis diabetes mellitus type 1 crohns disease rheumatoid arthritis immunological clinical outcomes reviewed provide evidence proofofconcept efficacy summarize current knowledge systematic review metaanalysis conducted total 8906 records reviewed 2 independent assessors 48 records included final quantitative analysis overall frequency serious adverse events low 0018 95 ci 00060051 immunological outcomes assessed quantitatively heterogeneity outcome assessments description well lack individual data randomized controlled studies medium risk bias due openlabel treatment without masking assessors patients intervention conclusion toleranceinducing cellbased therapies safe advocate harmonization study protocols trials investigating cellbased therapies adverse event reporting systematic inclusion immunological outcome measures clinical trials evaluating toleranceinducing cellbased treatment registration prospero registration number crd42020170557pmid34119672 doi101016 jautrev2021102873,0.0
novel prognostic score assess risk progression relapsingremitting multiple sclerosis patients eur j neurol 2021 apr 9 doi 101111 ene14859 online ahead printabstractbackground patientlevel prognostic value several features known associated increased risk converting relapsing remitting rr secondary phase sp multiple sclerosis ms remain limitedmethods among 262 rrms patients followed ten years assessed probability developing sp course based clinical conventional nonconventional magnetic resonance imaging mri parameters diagnosis two years used machine learning method random survival forests identify according minimal depth md predictive factors associated risk sp conversion combined compute secondary progressive risk score sprisc results observation period 69 26 patients converted spms number cortical lesions md247 age md330 diagnosis global cortical thinning md 165 cerebellar cortical volume loss md 215 cortical lesion load increase md315 first two years exerted greatest predictive effect three patients riskgroups identified highrisk group 85 46 55 patients entered sp phase 7 median years sprisc optimal cutoff estimated 177 showing specificity sensitivity 87 92 respectively overall accuracy 88conclusions sprisc yielded high performance identifying ms patients high probability develop spms can help improve management strategies findings premise larger prospective studies assess use clinical settingspmid33835665 doi101111 ene14859,0.0
predicting infection risk multiple sclerosis patients treated ocrelizumab retrospective cohort study cns drugs 2021 apr 13 doi 101007 s40263021008103 online ahead printabstractbackground ocrelizumab safety outcomes well evaluated clinical trials openlabel extension ole studies however risk factors infection patients multiple sclerosis ms receiving ocrelizumab extensively studied realworld settingobjective aim study examine factors determining risk selfreported infections antimicrobial use patients receiving ocrelizumab msmethods retrospective observational cohort study conducted patients receiving ocrelizumab royal melbourne hospital infection type number reported patients associations potential clinical laboratory risk factors selfreported infection antimicrobial use estimated using univariate multivariable logistic regression modelsresults total 185 patients included study total 176 infections reported 89 patients 461 antimicrobial use identified 47 patients 253 univariate analyses higher serum iga associated reduced odds infection 044 95 ci 025076 multivariable analyses older age 094 95 ci 088099 higher serum iga 037 95 ci 017080 higher serum igg 081 95 ci 067099 associated reduced odds infection older age 085 95 ci 075096 higher serum iga 023 95 ci 007079 associated reduced odds antimicrobial use whilst longer ms disease duration 122 95 ci 106141 higher expanded disability status scale edss score 199 95 ci 102386 associated increased odds antimicrobial useconclusions higher serum iga igg older age associated reduced odds infection findings highlight infection risk uniform patients ms receiving ocrelizumab substantiate need monitor immunoglobulin levels pretreatment whilst therapypmid33847902 doi101007 s40263021008103,0.0
investigating oligodendrocyte connexins heteromeric interactions cx32 mutant wildtype forms cx47 contribute modulate gap junction function glia 2021 apr 9 doi 101002 glia23999 online ahead printabstractoligodendrocytes express two gap junction forming connexins connexin 32 cx32 cx47 therefore formation heteromeric channels containing cx47 cx32 monomers might occur mutations cx47 cause pelizaeusmerzbacherlike disease type 1 pmld1 hereditary spastic paraparesis type 44 spg44 heteromer formation mutants cx32 may contribute pathogenesis disorders utilized electrophysiological antibodybased techniques examine possibility cells expressing cx32 cx47 paired cells expressing either cx32 cx47 properties indistinguishable produced cells expressing homotypic cx32 cx47 channels similarly pairing cells expressing cx32 cx47 cells expressing cx30 cx43 produced channels indistinguishable heterotypic cx32 cx30 cx47 cx43 channels respectively assessments performed cells expressing cx32 four mutant forms cx47 pi33m associated spg44 pp87s py269d pm283t associated pmld1 none mutants showed functional effect cx32 immunostained cells coexpressing cx32wt wild type cx47wt showed pearson correlation coefficient close zero suggesting overlap due chance py269d showed statistically significant negative correlation cx32 suggesting cx32 mutant overlap less expected chance coimmunoprecipitation cx32 cx47wt mutants show low levels coimmunoprecipitated protein overall data suggest interactions pmld1 spg44 mutants cx32 gap junctions contribute pathogenesis disorderspmid33835612 doi101002 glia23999,0.0
uptake attitudes immunizations people multiple sclerosis neurol clin pract 2021 aug 11 4 327334 doi 101212 cpj0000000000001099abstractobjective surveying multiple sclerosis ms population tested hypothesis influenza vaccine uptake meet public health targets vaccine misconceptions contribute lower desired uptakemethods spring 2020 surveyed participants north american research committee multiple sclerosis registry regarding vaccinations participants reported whether received hepatitis hepatitis b pneumococcal shingles varicella measles mumps rubella tetanus influenza vaccines participants received influenza vaccine last year reported reasons summarized responses descriptively using multivariable logistic regression assessed participant characteristics associated uptake seasonal influenza vaccineresults 5 244 eligible respondents 808 female mean sd age 618 101 years overall 430 2 161 5 032 participants reported neurologist ever asked immunization history percentage participants received seasonal flu vaccine last year ranged 591 among aged 1824 years 799 persons aged 65 years among get influenza vaccination common reasons personal preference 296 concerns possible adverse effects general 293 concerns vaccine worsen ms 237 conclusion vaccination uptake lower desired ms population compared existing recommendations including seasonal influenza misconceptions safety vaccination context ms personal preference appear play important roles vaccination choices highlighting importance education issuespmid34476124 pmcpmc8382432 doi101212 cpj0000000000001099,0.0
risk invasive fungal infections among patients treated disease modifying treatments multiple sclerosis comprehensive review expert opin drug saf 2021 apr 21112 doi 101080 1474033820211918673 online ahead printabstractintroduction disease modifying treatments commonly used treatment multiple sclerosis different opportunistic infections reported concerns also raised regarding risk invasive fungal infectionsareas covered clinical trials observational studies safety efficacy diseases modifying treatment multiple sclerosis reviewed data regarding occurrence invasive fungal infections reported papers evaluating following drugs reviewed rituximab ocrelizumab alemtuzumab fingolimod natalizumab dimethyl fumarate interferon glatiramer acetate cladribine teriflunomideexpert opinion overall occurrence invasive fungal infections low infective events reported among patients treated monoclonal antibodies fingolimod aspergillosis cryptococcal meningitidis representative fungal infections although common infections may difficult diagnose fatality rate often high reason screening protocols fungal infections must implemented clinical practice managing patients mspmid33880975 doi101080 1474033820211918673,0.0
mechanistic underpinning insideout concept autoimmunity multiple sclerosis ann clin transl neurol 2021 jun 22 doi 101002 acn351401 online ahead printabstractthe neuroinflammatory disease multiple sclerosis driven autoimmune pathology central nervous system however trigger autoimmune pathogenic process unknown ms models immunologically nave specificpathogenfree bred rodents support exogenous trigger infection validity outsidein pathogenic concept ms frequently challenged difficulty translate pathogenic concepts developed models effective therapies ms patient studies wellvalidated nonhuman primate multiple sclerosis models just like humans autoimmune pathogenic process develops experienced immune system trained prior infections rather support endogenous trigger data reviewed corroborate validity insideout pathogenic concept multiple sclerosis also provide plausible sequence events reminiscent wilkins primary lesion theory autoimmunity physiological response immune system excess antigen turnover diseased tissue primary lesion ii individuals developing autoimmune disease genetically predisposed high responders critical antigens data obtained multiple sclerosis brains reveal presence normally appearing white matter myelinated axons myelin sheaths locally dissociated enwrapped axon ie blistering ensuing disintegration axonmyelin units potentially causes excess systemic release posttranslationally modified myelin data obtained unique primate multiple sclerosis model revealed core pathogenic role t cells present normal repertoire hyperreact posttranslationally modified citrullinated myelinoligodendrocyte glycoprotein evoke clinical pathological aspects multiple sclerosispmid34156169 doi101002 acn351401,1.0
expression cyp24a1 multiple sclerosis risk genes peripheral blood indicates response vitamin d homeostatic inflammatory conditions genes immun 2021 jun 23 doi 101038 s41435021001446 online ahead printabstractalthough genetic epidemiological evidence indicates vitamin d insufficiency contributes multiple sclerosis ms serum levels vitamin d increase treatment cholecalciferol recent metanalyses indicate vitamin d form ameliorate disease genetic variation genes regulating vitamin d regulated vitamin d affect ms risk evaluated expression vitamin d responsive ms risk genes used assess vitamin d response immune cells peripheral blood mononuclear cells pbmcs isolated healthy controls people ms treated dimethyl fumarate assayed changes expression vitamin d responsive ms risk vdrms genes response treatment 25 hydroxy vitamin d presence absence inflammatory stimuli expression cyp24a1 vdrms genes significantly altered pbmcs treated vitamin d homeostatic inflammatory models gene expression ms samples similar responses controls lower initial expression risk genes vitamin d treatment abrogated differences expression cyp24a1 ms risk genes blood immune cells indicate vitamin d response enable assessment immunological response vitamin d clinical trials therapypmid34163021 doi101038 s41435021001446,0.0
tspo levels multiple sclerosis lesions reflect microglial density rather activation state nat rev neurol 2021 jun 29 doi 101038 s41582021005335 online ahead printno abstractpmid34188236 doi101038 s41582021005335,0.0
ixekizumab patients plaque psoriasis affected multiple sclerosis case report sultan qaboos univ med j 2021 aug 21 3 488490 doi 1018295 squmj42021021 epub 2021 aug 29abstractmultiple sclerosis ms autoimmune demyelinating disorder central nervous system shares similar immunopathogenic mechanisms chronic plaque psoriasis overexpression th17 pathway report 50yearold male patient ms severe chronic plaque psoriasis presented hospital virgen de la victoria mlaga spain 2019 successfully treated ixekizumab antiinterleukin il 17a il17a f monoclonal antibody treatment achieved complete skin clearance ie psoriasis area severity index 100 response adverse event evidence progression neurological disease eitherpmid34522419 pmcpmc8407899 doi1018295 squmj42021021,1.0
lower urinary tract disorders multiple sclerosis patients prevalence clinical features response treatments neurourol urodyn 2021 jun 3 doi 101002 nau24687 online ahead printabstractaims lower urinary tract symptoms common multiple sclerosis ms great impact quality life evaluated prevalence characteristics urological symptoms cohort patients msmethods crosssectional study conducted consecutive patients ms attending center 2018 evaluated prevalence clinical features response symptomatic treatments lower urinary tract disorders investigated relationship clinical demographic features data urodynamic studies also collectedresults cohort 806 patients overall prevalence urological symptoms 529 urgency frequent symptom 594 symptomatic patients higher disability longer disease duration later age onset greater mean age time evaluation urinary disorders frequent patients progressive disease women 418 patients treatment urological disorder 815 reported improvement symptomsconclusion urinary disorders patients ms high prevalence early correct characterization types symptoms early targeted therapeutic strategy essential improve patients quality life avoid future complicationspmid34082481 doi101002 nau24687,0.0
antioxidative effects silymarin reduction liver complications fingolimod patients relapsingremitting multiple sclerosis clinical trial study j biochem mol toxicol 2021 may 2e22800 doi 101002 jbt22800 online ahead printabstractmultiple sclerosis ms chronic disease affects central nervous system characterized inflammation demyelination degenerative changes relapsingremitting ms rrms common form ms fingolimod fty720 oncedaily diseasemodifying agent approved treat rrms binds sphingosine 1phosphate receptors milk thistle silybum marianum sm herb generally used protect liver antioxidant antifibrotic effects purpose study evaluate effects silymarin reducing liver complications fty720 patients rrms decrease oxidative stress plays important role pathogenesis disease fortyeight patients rrms divided two groups using random assignment placebo drugtreated groups participants intervention control groups took fty720 silymarin placebo without silymarin per day six months findings showed significant reduction level alt ast reduction main pathogenic factors ms containing malondialdehyde also significant rise total antioxidant capacity total thiol groups serum patients treated silymarin compared placebo group outcomes propose practical effects silymarin multiple sclerosis reduction hepatic side effects fingolimodpmid33934443 doi101002 jbt22800,1.0
multifaceted involvement microglia gray matter pathology multiple sclerosis stem cells 2021 mar 22 doi 101002 stem3374 online ahead printabstractin inflammatory demyelinating neurodegenerative disease multiple sclerosis ms increasing interest gray matter pathology neuronal loss cortical atrophy correlate disability disease progression ms therapeutics fail significantly slow stop neurodegeneration microglia central nervous system cns resident macrophages extensively involved white matter ms pathology also implicated gray matter pathology similarly neurodegenerative diseases synaptic axonal neuronal degeneration microglia display regional heterogeneity within cns reflects highly plastic nature ability deliver contextdependent responses tailored demands microenvironment therefore microglial roles ms gray matter part reflect part diverge white matter present review summarizes current knowledge microglial involvement gray matter changes ms demyelination synaptic damage neurodegeneration evidence implicating microglia pathology neuroprotection repair understanding microglial physiology pathophysiology increases describe moving toward potential therapeutic applications ms harnessing microglia protect regenerate cns alphamed press 2021 significance statement gray matter pathology multiple sclerosis great current interest recent advances live brain imaging reveal present earliest disease stages unlike white matter pathology significantly correlated disability microglia resident immune cells brain first line defense heterogeneity responses depending whether reside gray white matter understanding microglial responses gray matterspecific cues will shed light multiple sclerosis pathological processes guide therapeutic strategies targeting gray matter neuroprotectionan unmet need avoid treat disabilitypmid33754376 doi101002 stem3374,1.0
multiple sclerosis linked mapk erk overactivity microglia j mol med berl 2021 may 5 doi 101007 s00109021020804 online ahead printabstractreassessment published observations patients multiple sclerosis ms suggests microglial malfunction due inappropriate activity mitogenactivated protein kinase pathway erk mapkerk observations regard biochemistry well epigenetics indicate involvement pathway recent preclinical research neurodegeneration already pointed towards role mapk pathways particular mapkerk important microglia overactive mapk identified disturb local oligodendrocytes can lead locoregional demyelination hallmark ms constitutes new concept pathophysiology ms besides prevailing view ie autoimmunity acknowledged risk factors ms ebv infection hypovitaminosis d smoking downregulate mapkerk negative feedback phosphatases normally regulate mapkerk activity consequently factors may contribute inappropriate mapkerk overactivity thereby neurodegeneration also mapkerk overactivity microglia factor pathophysiology ms explain ongoing neurodegeneration ms patients despite optimized immunosuppressive immunomodulatory treatment currently patients progressive disease effective treatment exists refractory ms targeting cause overactive mapkerk microglia merits investigation phenomenon may imply novel treatment approachpmid33948692 doi101007 s00109021020804,1.0
multiple sclerosis increase risk preeclampsia systematic review metaanalysis hypertens pregnancy 2021 may 1716 doi 101080 1064195520211921792 online ahead printabstractobjective investigated via systematic review metaanalysis whether multiple sclerosis ms associated risk preeclampsia pe methods eligible studies pooled odds ratios ors confidence intervals cis pe pregnant women ms compared pregnant women without using fixedeffects model i2 measured heterogeneity studiesresults eight eligible studies 9 cohorts included pregnant women ms excess risk pe compared pregnant women without ms pooled 099 95 ci 089 109 i2 000 conclusion ms associated pepmid33999737 doi101080 1064195520211921792,0.0
interactions alslinked fus nucleoporins associated defects nucleocytoplasmic transport pathway nat neurosci 2021 may 31 doi 101038 s41593021008599 online ahead printabstractnucleocytoplasmic transport nct decline occurs aging neurodegeneration investigated nct pathway models amyotrophic lateral sclerosisfused sarcoma alsfus expression alsfus led reduction nct nucleoporin nup density within nuclear membrane human neurons fus nups found interact independently rna cells alter phaseseparation properties vitro fusnup interactions localized nuclear pores enriched nucleus control neurons versus cytoplasm mutant neurons data indicate effect alslinked mutations cytoplasmic mislocalization fus rather physiochemical properties protein underlie reported nct defects aberrant interaction mutant fus nups underscored studies drosophila whereby reduced nup expression rescued multiple toxic fusinduced phenotypes including abnormal nuclear membrane morphology neuronspmid34059832 doi101038 s41593021008599,0.0
type interferon detection autoimmune diseases challenges clinical applications expert rev clin immunol 2021 jun 7 doi 101080 1744666x20211939686 online ahead printabstractintroduction accumulating data highlights dysregulation type interferon ifn pathways plays central role pathogenesis several systemic organ specific autoimmune diseases advances understanding role type ifns disorders can lead targeted drug development well establishing potential disease biomarkersareas covered summarize current knowledge regarding role type ifns major systemic well organ specific autoimmune disorders including prominent inflammatory cns disorders like multiple sclerosisexpert opinion type ifn involvement clinical associations wide spectrum autoimmune diseases represents promising area research aiming unveil common pathogenetic pathways systemic organ specific autoimmunitypmid34096436 doi101080 1744666x20211939686,0.0
cns demyelination associated immune dysregulation novel ctla4 variant mult scler 2021 jun 71352458520963896 doi 101177 1352458520963896 online ahead printabstractbackground cytotoxic tlymphocyte antigen4 ctla4 pathway acts negative immune regulator tcell activation promotes selftolerancecase report first case biopsyproven central nervous system inflammatory demyelination context primary immunodeficiency novel ctla4 variantconclusion case significant implications development novel treatments autoimmune conditions including multiple sclerosis emphasises need caution clinical use ctla4 immune checkpoint inhibitors history inflammatory demyelinationpmid34097529 doi101177 1352458520963896,1.0
phosphorylation transactive response dna binding proteinof 43 kda promotes cytoplasmic aggregation modulates function tau mrna stability exon 10 alternative splicing j neurochem 2021 jun 9 doi 101111 jnc15450 online ahead printabstracttransactive response dnabinding protein 43 kda tdp43 promotes tau mrna instability tau exon 10 inclusion aggregation phosphorylated tdp43 associated amyotrophic lateral sclerosis als frontotemporal lobar degeneration ftld ck1 phosphorylates tdp43 multiple sites enhances cytoplasmic aggregation modulates function tau mrna processing determine roles tdp43 sitespecific phosphorylation localization aggregation function tau mrna processing tdp43 mutated alanine aspartic acid ser379 ser403 404 ser409 410 block mimic phosphorylation sitespecific phosphorylation tdp43 mutants ck1 studied vitro cultured cells cytoplasmic nuclear tdp43 phosphotdp43 analyzed western blots aggregation tdp43 assessed immunostaining level ripainsoluble tdp43 gfp tailed tau 3utr minitau gene pci si9li10 used study tau mrna stability alternative splicing tau exon 10 found phosphoblocking mutations tdp43 ser379 ser403 404 ser409 410 effectively phosphorylated ck1 compared tdp43 higher level phosphorylated tdp43 cytoplasm observed phosphomimicking mutations sites enhanced cytoplasmic aggregation tdp43 gfp expression inhibited phosphoblocking mutants tdp43 tau exon 10 inclusion enhanced phosphoblocking mutations ser379 ser403 404 phosphorylation tdp43 ser379 ser 403 404 ser409 410 primes phosphorylation ck1 promotes tdp43 cytoplasmic aggregation modulates function tau mrna processing sitespecific mannerpmid34107054 doi101111 jnc15450,0.0
glucan particles novel adjuvant induction experimental autoimmune encephalomyelitis cell immunol 2021 may 21 366104383 doi 101016 jcellimm2021104383 online ahead printabstractfor 70 years experimental autoimmune encephalomyelitis eae induced myelin autoantigens emulsified complete freunds adjuvant cfa significant side effects pain inflammation tissue necrosis injection site 1 3dglucan particles gps hollow microcapsules prepared saccharomyces cerevisiae cell walls induce potent th17 cell responses without causing strong injection site tissue reactions evaluated potential gps complexed neuroantigens induce eae avoiding undesirable side effects gps loaded myelin oligodendrocyte glycoprotein 3555 mog3555 proteolipid protein 139151 plp139151 peptides effectively induced eae c57bl 6 mice sjl mice disease severity cns pathology immune responses comparable gp cfaimmunized mice importantly injection gps resulted significantly decreased inflammation compared cfa posit use gps provides alternative means inducing eae results comparable disease less discomfort animalspmid34111646 doi101016 jcellimm2021104383,1.0
multiple sclerosis prodrome nat rev neurol 2021 jun 21 doi 101038 s41582021005193 online ahead printabstracta prodrome early set signs symptoms findings occur onset typical symptoms disease prodromal phases well recognized several neurological inflammatory diseases possibility prodrome multiple sclerosis ms received relatively little attention past years perspective summarize currently known ms prodrome including possible duration clinical features potential biomarkers also consider insights lessons can learned knowledge research prodromal phases diseases better understanding ms prodrome profound clinical implications enable earlier recognition ms earlier initiation treatments reduce relapse rates longterm disability knowledge ms prodrome also affect research causes ms putative risk factors must reevaluated light ms prodrome conclude outlining major knowledge gaps propose future initiativespmid34155379 doi101038 s41582021005193,0.0
efficacy mycophenolate mofetil versus cyclophosphamide systemic sclerosisrelated interstitial lung disease systematic review metaanalysis clin rheumatol 2021 jun 2 doi 101007 s10067021057945 online ahead printabstractobjective study systematically compares efficacy adverse events mycophenolate mofetil mmf cyclophosphamide cyc patients systemic sclerosisrelated interstitial lung disease sscild methods embase pubmed databases systematically searched find relevant studies quality assessment study selection data extraction independently conducted two reviewers mean changes forced vital capacity fvc diffusing capacity carbon monoxide dlco patients selected primary outcome measures stata software used pooled analysisresults among 284 titles screened multiple databases six studies met inclusion criteria one randomized controlled trial three prospective observational studies two retrospective observational studies summary weighted mean difference wmd fvc change mmf group compared cyc group 117 95 ci 2713 0373 p 0137 summary wmd dlco change mmf group compared cyc group 2245 95 ci 0258 4232 p 0027 studies enrolled showed adverse events less common mmf groupconclusions efficacy mmf respect fvc dlco improvement comparable cyc mmf preferred basis occurrence adverse events key points systematic review metaanalysis conducted compare efficacy adverse events mycophenolate mofetil cyclophosphamide patients systemic sclerosisrelated interstitial lung disease efficacy mmf respect fvc dlco improvement comparable cyc mmf preferred basis occurrence adverse eventspmid34080081 doi101007 s10067021057945,0.0
disease biomarkers multiple sclerosis current serum neurofilament light chain perspectives neurodegener dis manag 2021 jul 1 doi 102217 nmt20200058 online ahead printabstractthe continuous neuroinflammatory neurodegenerative pathology multiple sclerosis ms results irreversible accumulation physical cognitive disability reliable early detection ms disease processes can aid diagnosis monitoring treatment management ms patients recent assay technological advancements now allow reliable quantification serumbased neurofilament light chain snfl levels provide temporal information regarding degree neuroaxonal damage relationship predictive value snfl clinical cognitive outcomes paraclinical measures treatment response reviewed snfl measurement emerging noninvasive diseaseresponsive ms biomarker currently utilized research clinical trial settings understanding snfl confounders assay standardization will allow clinical implementation biomarkerpmid34196596 doi102217 nmt20200058,0.0
targeting inflammasomes treat neurological diseases ann neurol 2021 jul 5 doi 101002 ana26158 online ahead printabstractinflammasomes multimeric protein complexes can sense plethora microbe damageassociated molecular signals play important roles innate immunity key regulators inflammation health disease inflammasomemediated processing secretion proinflammatory cytokines interleukin 1 il1 il18 induction pyroptosis proinflammatory form cell death associated development progression common immunemediated degenerative central nervous system cns diseases alzheimers disease multiple sclerosis brain injury stroke epilepsy parkinsons disease amyotrophic lateral sclerosis growing number pharmacological compounds inhibiting inflammasome activation signalling shows therapeutic efficacy preclinical models aforementioned disease conditions illustrate regulatory mechanisms inflammasome activation cns homeostasis tissue injury highlight evidence inflammasome activation mechanistic underpinning wide range cns diseases critically discuss promise potential limitations therapeutic strategies aim inhibit inflammasome components neurological disorders article protected copyright rights reservedpmid34219266 doi101002 ana26158,0.0
emerging role white matter lesions cerebrovascular disease eur j neurosci 2021 jul 7 doi 101111 ejn15379 online ahead printabstractwhite matter lesions implicated setting stroke dementia intracerebral haemorrhage several cerebrovascular conditions migraine various neuroimmunological diseases like multiple sclerosis disorders metabolism mitochondrial diseases others much understood vis vis neuroimmunological conditions knowledge pathophysiology lesions role implications management cerebrovascular diseases stroke especially elderly limited several clinical assessment tools available delineating white matter lesions clinical practice however incorporation clinical decisionmaking specifically prognosis management patients suboptimal use standards care article sought provide overview current knowledge recent advances pathophysiology well clinical radiological assessment white matter lesions focus development progression clinical implications cerebrovascular diseases key indications clinical practice recommendations future areas research also discussed finally conceptual proposal putative mechanisms underlying pathogenesis white matter lesions cerebrovascular disease presented understanding pathophysiology white matter lesions mediate outcomes important develop therapeutic strategiespmid34233379 doi101111 ejn15379,0.0
correction targeting sphingosine1phosphate signaling immunemediated diseases beyond multiple sclerosis drugs 2021 jul 30 doi 101007 s4026502101577z online ahead printno abstractpmid34328627 doi101007 s4026502101577z,0.0
establishment integrationfree human induced pluripotent stem cell line tjci001a normal bone marrowderived mesenchymal stem cells stem cell res 2021 aug 3 55102484 doi 101016 jscr2021102484 online ahead printabstractbone marrowderived mesenchymal stem cells bmmscs possess excellent therapeutic potential treatment various diseases including graftversushost disease rheumatoid arthritis osteoarthritis multiple sclerosis generated induced pluripotent stem cell ipsc line bmmscs employing nonintegrating episomal vector generated ipscs expressed pluripotency markers showed normal karyotype exhibited potential vitro differentiation three germ layers ipsc line can used healthy control stem cell therapeutics disease modeling studiespmid34371346 doi101016 jscr2021102484,0.0
multiple sclerosis gut microbiome current research perspective brain nerve 2021 aug 73 8 899903 doi 1011477 mf1416201857abstractmultiple sclerosis ms neurological disease alterations gut microbiota can confirmed metagenomic analysis addition 16s rrna analysis whole metagenomic analysis well metabolomic analysis applied field convincingly proved reduction short chain fatty acids characterizes intestinal environment patients ms research needed elucidate mechanisms responsible alterations gut microbiome patients ms characterization virome may shed light onpmid34376596 doi1011477 mf1416201857,0.0
multiple sclerosis phenotypes continuum role neurologic reserve neurol clin pract 2021 aug 11 4 342351 doi 101212 cpj0000000000001045abstractpurpose review review presents hypothesis loss neurologic reserve explains onset progressive multiple sclerosis prms recent findings evidence supporting separate classification prms relapsing multiple sclerosis rms limited explain prms response patients therapysummary argue multiple sclerosis ms progresses along continuum rms prms differing levels neurologic reserve accounting phenotypic differences early ms inflammation causes brain atrophy symptoms buffered neurologic reserve brain loss normal aging ms continues reserve depleted effects subclinical ms disease activity aging unmasked manifesting prms therapies show limited benefit prms patients older fewer inflammatory events effects aging cause continued loss neurologic function even inflammation terminated loss neurologic reserve means patients prms recover function unlike patients rmspmid34476126 pmcpmc8382415 doi101212 cpj0000000000001045,0.0
loss neurologic reserve progressive multiple sclerosis paradigm shift neurol clin pract 2021 aug 11 4 271272 doi 101212 cpj0000000000001106no abstractpmid34484925 pmcpmc8382419 doi101212 cpj0000000000001106,0.0
discovery antissa antibodies stroke investigations young adults impact j stroke cerebrovasc dis 2021 jun 15 30 8 105896 doi 101016 jjstrokecerebrovasdis2021105896 online ahead printabstractobjectives french national guidelines recommend searching antissa antibodies secondline assessment stroke adults 55 years age absence identified etiology aimed assess impact finding antissa antibodies etiological investigations stroke young adultsmethods medical files patients 55 years age admitted single stroke unit fiveyear period antissa antibodies positive retrospectively analyzedresults twelve patients included 9 women median age 485 years rate antissa antibody positivity 16 95 confidence interval 071255 12 735 admissions etiologies 12 ischemic events based toast classification largeartery atherosclerosis n 1 cardioembolism n 1 smallvessel disease n 1 determined etiology n 3 multiple etiology n 1 determined etiology n 5 connective tissue disease ctd discovered 8 12 patients 1 primary sjgrens syndrome 1 mixed ctd 1 systemic sclerosis 2 antiphospholipid syndromes 1 undetermined ctd 2 lupus antissa antibodies directly responsible stroke 12 cases link autoimmune disease neurological vascular episode hypothesized four patients never influenced therapeutic decisionconclusions finding antissa antibodies etiological assessment stroke young adults rare however may worthwhile refer patient rheumatologist internist ctd may discovered may require specific followuppmid34144337 doi101016 jjstrokecerebrovasdis2021105896,0.0
antinociceptive profile arn19702 2ethylsulfonylphenyl 2s 4 6fluoro1 3benzothiazol2yl 2methylpiperazin1yl methanone novel orally active nacylethanolamine acid amidase inhibitor animal models j pharmacol exp ther 2021 may 13jpetar2021000674 doi 101124 jpet121000674 online ahead printabstractnacylethanolamine acid amidase naaa nterminal cysteine hydrolase stops physiological actions palmitoylethanolamide pea endogenous lipid messenger activates transcription factor peroxisome proliferatoractivated receptor previously reported compound arn19702 2ethylsulfonylphenyl 2s 4 6fluoro1 3benzothiazol2yl 2methylpiperazin1yl methanone orally active reversible naaa inhibitor median inhibitory concentration ic50 human naaa 230 nm produces remarkable protective effects multiple sclerosis mice present study assessed profile arn19702 mouse rat models acute neuropathic pain oral administration male mice attenuated dosedependent manner spontaneous nocifensive response elicited intraplantar formalin injection hypersensitivity caused intraplantar carrageenan injection paw incision sciatic nerve ligation male rats arn19702 reduced nociception associated paclitaxelinduced neuropathy without development subacute antinociceptive tolerance finally arn19702 30 mg kg oral produce placepreference alter exploratory motor behavior male mice findings support conclusion naaa suitable molecular target discovery efficacious analgesic drugs devoid rewarding potential significance statement evaluated pharmacological profile orally bioavailable naaa inhibitor arn19702 mouse rat models neurogenic inflammatory pain compounds potential rewarding sedative effects also examined conclude arn19702 exhibits broad analgesic profile can generalized across rodent species findings point naaa control node processing neuropathic inflammatory pain arn19702 lead uncover novel pain therapeutics devoid addictive potentialpmid33986036 doi101124 jpet121000674,0.0
first measured retinal nerve fiber layer thickness rrms can used biomarker course disease threshold value discussions j neurol 2021 feb 19 doi 101007 s0041502110469x online ahead printabstractbackground peripapillary retinal nerve fiber layer thickness correlates radiological clinical parameters patients msobjective aim study investigate use first measured prnfl thickness predictor disease course patients rrmsmethods one hundred thirty seven rrms patients enrolled study within first 5 years illness patients followed 341 months edss used assess disability status determine whether first measured prnfl thickness using proportional hazards models predicts risk disability worseningresults mean disease duration 261 months disability worsening detected 36 patients tertilebased groups formed according prnfl thickness group lowest prnfl thickness 28fold increase risk disability worsening compared group highest risk higher first 2 years study hr 348 p 0008 conclusion first measured prnfl thickness rrms patients can predict risk disability worsening risk disability worsening early period higher group lowest prnfl valuepmid33606071 doi101007 s0041502110469x,0.0
microglial phagocytosis neurons neurodegeneration regulation j neurochem 2021 feb 20 doi 101111 jnc15327 online ahead printabstractthere growing evidence excessive microglial phagocytosis neurons synapses contributes multiple brain pathologies rnaseq genome wide association gwas studies linked multiple phagocytic genes neurodegenerative diseases knockout phagocytic genes found protect neurodegeneration animal models suggesting excessive microglial phagocytosis contributes neurodegeneration review recent evidence microglial phagocytosis live neurons synapses causes neurodegeneration animal models alzheimers disease tauopathies parkinsons disease frontotemporal dementias multiple sclerosis retinal degeneration neurodegeneration induced ischaemia infection ageing also review factors regulating microglial phagocytosis neurons including nucleotides frackalkine phosphatidylserine calreticulin udp cd47 sialylation complement galectin3 apolipoprotein e phagocytic receptors siglec receptors cytokines microglial epigenetics expression profile factors may potential treatment targets prevent neurodegeneration mediated excessive microglial phagocytosis live neurons synapsespmid33608912 doi101111 jnc15327,0.0
effectiveness natalizumab vs fingolimoda comparison international registry studies mult scler relat disord 2021 may 8 53103012 doi 101016 jmsard2021103012 online ahead printabstractbackground natalizumab fingolimod first preparations recommended disease breakthrough priorly treated relapsingremitting multiple sclerosis three published headtohead studies two showed natalizumab effective prevent relapses edss worseningmethods reanalyzing original published results msbase france denmark using uniform methodologies aimed identifying effects differences methodology mspopulations reevaluating differences effectiveness two drugs gained access copies individual amended databases pooled data used uniform inclusion exclusion criteria statistical methods inverse probability treatment weightingresults pooled analyses comprised 968 natalizumab 1479 fingolimod treated patients ontreatment natalizumab fingolimod relapse rate ratio 077 p0004 hazard ratio hr first relapse 082 p0030 hr sustained edss improvement 14 p0009 modest differences original published studies replication study conclusions three original studies remained unchanged two natalizumab effective third difference natalizumab fingolimodconclusion results largely invariant epidemiological statistical methods differed ms populations generally advantage natalizumab confirmedpmid34116480 doi101016 jmsard2021103012,0.0
pathologysupported genetic testing method disability prevention multiple sclerosis ms part ii insights two ms cases metab brain dis 2021 mar 12 doi 101007 s11011021007129 online ahead printabstractin part review evaluated scientific evidence metabolic model multiple sclerosis ms part ii outlines implementation adaptive pathologysupported genetic testing psgt algorithm aimed preventing reversing disability two illustrative ms cases starting questionnairebased risk assessment including family history lifestyle factors measurement iron vitamin b12 vitamin d cholesterol homocysteine levels identified biochemical deficits cases case 1 following psgt program 15 years expanded disability status scale edss 20 neurological sequelae together preserved brain volume magnetic resonance imaging mri novel form iron deficiency identified case 1 biochemical testing hospital submission due ms symptoms showed low serum iron ferritin transferrin saturation hematological status erythrocyte sedimentation rate measurement systemic inflammation remained normal case 2 unable walk unaided edss improved 65 40 12 months implementation psgt program amelioration suboptimal biochemical markers changes diet lifestyle allowing regain independence genotypephenotype correlation using pathway panel functional single nucleotide variants snvs facilitate clinical interpretation whole exome sequencing wes elucidated underlying metabolic pathways related biochemical deficits cure ms will remain elusive goal separated nutritional support required production maintenance myelin can achieved lifelong investment wellnesspmid33710528 doi101007 s11011021007129,1.0
assessment genetic contribution brain mri lesion load atrophy measures multiple sclerosis patients eur j neurol 2021 apr 17 doi 101111 ene14872 online ahead printabstractbackground multiple sclerosis ms susceptibility influenced genetics however little known genetic determinants disease expression aimed assessing genetic factors influencing quantitative neuroimaging measures two cohorts progressive pms relapsingremitting rrms patientsmethods ninetynine pms 214 rrms patients underwent 3t brain mri scan measurement five mri metrics including t2 lesion volumes measures white matter grey matter deep grey matter hippocampal volumes candidate pathway strategy adopted gene set analysis carried estimate cumulative contribution genes mri phenotypes adjusting relevant confounders followed snp regression analysisresults seventeen kegg pathways 42 gene ontology go terms tested additionally included analysis genes enriched expression brain cells gene set analysis revealed differential pattern association across two cohorts processes related sodium homeostasis associated grey matter volume pms p0002 whereas inflammatoryrelated go terms like adaptive immune response regulation inflammatory response appeared associated t2 lesion volume rrms p0004 p0008 respectively snps rs7104613t mapping spon1 gene associated reduced deep grey matter volume beta0731 p32107 pms found evidence association white matter volume rs740948a mapping sema3a gene beta2204 p55106 rrmsconclusions data suggest different pattern associations mri metrics functional processes across ms disease courses suggesting different phenomena implicated mspmid33864731 doi101111 ene14872,0.0
cardiac autonomic function patients early multiple sclerosis clin auton res 2021 mar 4 doi 101007 s1028602100790w online ahead printabstractpurpose cardiac autonomic dysfunction reported patients longstanding multiple sclerosis ms however data early disease limited present study aimed evaluating cardiac autonomic function patients early ms context white matter metabolic status potentially affect functions autonomic brain centersmethods cardiac sympathetic baroreflex cardiovagal responses valsalva maneuver orthostatic test stroop test evaluated 16 early treatmentnave patients relapsingremitting ms 14 healthy participants proton magnetic resonance spectroscopic imaging mrsi brain performed eight ms patients eight controlsresults valsalva maneuver outcomes comparable patients controls baseline norepinephrine levels lower p 0027 ms patients compared controls patients higher heart rate p 0034 lower stroke volume p 0008 similar blood pressure cardiac output norepinephrine increments baseline 2 min orthostatic test compared controls ms patients controls differ responses stroop test mrsi showed lower total nacetylaspartate total creatine p 0038 higher myoinositol total creatine p 0013 ms lesions compared nonlesional white matterconclusion results show normal cardiac sympathetic baroreflex cardiovagal function ms patients relapsingremitting ms lesions postacute early resolving stagetrial registration study registered clinicaltrialsgov identifier nct03052595 complies strobe checklist cohort casecontrol crosssectional studiespmid33665745 doi101007 s1028602100790w,0.0
characterization natural variant human ndp52 functional consequences mitophagy cell death differ 2021 mar 15 doi 101038 s41418021007663 online ahead printabstractthe role mitophagy process allows removal damaged mitochondria cells remains unknown multiple sclerosis ms disease found associated dysfunctional mitochondria qualitatively quantitatively studied main players pink1mediated mitophagy peripheral blood mononuclear cells pbmcs patients relapsingremitting ms found variant c491ga rs550510 pg140e ndp52 one major mitophagy receptor genes associated ms cohort characterization variant discovered residue 140 human ndp52 crucial modulator ndp52 lc3c binding promoting formation autophagosomes order drive efficient mitophagy addition found pbmc population ndp52 mainly expressed b cells ensuring efficient mitophagy able limit production proinflammatory cytokine tnf following cell stimulation sum results contribute better understanding role ndp52 mitophagy underline first time possible role ndp52 mspmid33723372 doi101038 s41418021007663,0.0
critical systematic review current evidence effects physical exercise whole regional grey matter brain volume populations risk neurodegeneration sports med 2021 apr 16 doi 101007 s40279021014536 online ahead printabstractbackground despite intriguing potential physical exercise able preserve even restore brain volume grey matter volume particular tissue essential cognitive physical functionno reviews far synthesized existing knowledge randomized controlled trials investigating exerciseinduced changes brains grey matter volume populations risk neurodegeneration objective critically review existing evidence regarding topicmethods systematic search carried medline embase databases primo april 2020 identify randomized controlled trials evaluating effects aerobic training resistance training concurrent training brain grey volume changes mri adult clinical healthy elderly populationsresults total 20 articles 19 rcts evaluating 312 months aerobic resistance concurrent training identified included involving total 1662 participants populations healthy older adults older adults mild cognitive impairment alzheimers disease adults schizophrenia multiple sclerosis major depression studies indicated positive effectalthough modestof physical exercise certain regions brain grey matter volume majority study findings neutral ie effects small effect sizes quite divergent across populations metaanalyses showed different exercise modalities failed elicit substantial effects whole brain grey volume hippocampus volume although rather large confidence interval width ie variability conclusion altogether current evidence effects physical exercise whole regional grey matter brain volume appear sparse inconclusive support physical exercise potent previously proposed comes affecting brain grey matter volumepmid33861414 doi101007 s40279021014536,0.0
classification criteria intermediate uveitis nonpars planitis type j ophthalmol 2021 apr 8s00029394 21 001793 doi 101016 jajo202103054 online ahead printabstractpurpose determine classification criteria intermediate uveitis nonpars planitis type iu npp also known undifferentiated intermediate uveitis design machine learning cases iunpp 4 intermediate uveitidesmethods cases intermediate uveitides collected informaticsdesigned preliminary database final database constructed cases achieving supermajority agreement diagnosis using formal consensus techniques cases split training set validation set machine learning using multinomial logistic regression used training set determine parsimonious set criteria minimized misclassification rate among intermediate uveitides resulting criteria evaluated validation setresults five hundred eightynine cases intermediate uveitides including 114 cases iunpp evaluated machine learning overall accuracy intermediate uveitides 998 training set 993 validation set 95 confidence interval 961 999 key criteria iunpp included unilateral bilateral intermediate uveitis neither 1 snowballs vitreous 2 snowbanks pars plana key exclusions included 1 multiple sclerosis 2 sarcoidosis 3 syphilis misclassification rates pars planitis 0 training set 0 validation set respectivelyconclusions criteria iunpp low misclassification rate appeared perform well enough use clinical translational researchpmid33839089 doi101016 jajo202103054,0.0
chpg enhances bdnf myelination cuprizonetreated mice astrocytic metabotropic glutamate receptor 5 glia 2021 apr 3 doi 101002 glia24003 online ahead printabstractit well recognized astrocytes can produce factors known affect myelination process one factor brainderived neurotrophic factor bdnf can enhance differentiation oligodendrocyte lineage cells following demyelinating lesion previous work indicated enhancing astrocytederived bdnf via injection general agonist group ii metabotropic glutamate receptors mglurs lesion increased myelin proteins cuprizone model demyelination 4 hr determine observation potential therapeutic significance now use specific mglur agonist 2chloro5hydroxyphenylglycine chpg binds mglur5 examine effects myelination clinically relevant approach peripheral injection initial studies intraperitoneal injection chpg resulted increase myelin proteins within lesioned corpus callosum effects blocked either bdnf chpg receptor mglur5 deleted glial fibrillary acidic protein gfap + astrocytes bdnf receptor tropomyosin receptor kinase b trkb deleted proteolipid protein plp + oligodendrocytes moreover injection chpg 2 weeks elevated bdnf myelin proteins also enhanced myelination reversed behavioral deficits interestingly effects myelin myelin proteins seen control animals indicating lesion critical eliciting effects taken together data suggest mglur agonist chpg may potential therapeutic strategy treating demyelinating diseases works enhancing release bdnf astrocytespmid33811383 doi101002 glia24003,1.0
growing role s100b protein putative therapeutic target neurological nonneurological disorders neurosci biobehav rev 2021 may 7s01497634 21 001986 doi 101016 jneubiorev202104035 online ahead printabstracts100b calciumbinding protein mainly expressed astrocytes also localized definite neural extraneural cell types presence biological fluids widely recognized reliable biomarker active injury growing evidence now indicates high levels s100b suggestive pathogenic processes different neural also extraneural disorders indeed modulation s100b levels correlates occurrence clinical toxic parameters experimental models diseases alzheimers parkinsons diseases amyotrophic lateral sclerosis muscular dystrophy multiple sclerosis acute neural injury inflammatory bowel disease uveal retinal disorders obesity diabetes cancer thus directly linking levels s100b pathogenic mechanisms general deletion inactivation protein causes improvement disease whereas overexpression administration induces worse clinical presentation scenario reasonably proposes s100b common therapeutic target several different disorders also offering new clues individuate possible unexpected connections among diseasespmid33971224 doi101016 jneubiorev202104035,0.0
cervical spinal degenerative disease multiple sclerosis eur j neurol 2021 apr 5 doi 101111 ene14855 online ahead printabstractbackground purpose root cord irritation cervical spinal degenerative disease may share clinical features progressive multiple sclerosis ms diagnostic overshadowing may occur hypothesized cervical stenotic spinal degenerative disease commoner progressive ms compared controlsmethods retrospective casecontrol study 111 cases 56 progressive ms 55 controls conducted five types cervical spinal degenerative disease disc degeneration posterior disc protrusion endplate changes canal stenosis foraminal stenosis assessed objectively magnetic resonance imaging using published scales multivariable regression analysis performedresults moderatetosevere cervical spinal degeneration occurred frequently progressive ms compared controls multivariable regression foraminal stenosis three times likely progressive ms odds ratio 320 95 ci127 809 p0014 severe p0009 finding confirmed retrospective evaluation clinical radiology reports population foraminal stenosis twice likely progressive ms compared relapsingremitting msconclusions people progressive ms susceptible foraminal stenosis higher index suspicion cervical spinal degenerative disease required appropriate neurological symptoms occur setting progressive ms guide appropriate treatment monitoringpmid33817913 doi101111 ene14855,0.0
cb1 receptor differentially regulates ifn production vitro experimental autoimmune encephalomyelitis cannabis cannabinoid res 2020 oct 30 doi 101089 can20200046 online ahead printabstractintroduction activation peripheral immune system infiltration immune cells central nervous system key features experimental autoimmune encephalomyelitis eae model exploring endocannabinoid system works modulate response can better understand exogenous cannabinoids thc might used modulate immune responses multiple sclerosis patients materials methods study examined role cb1 receptor ifn il17a production eae model vitro stimulations naive splenocytes using cnr1 mice wildtype wt littermates also introduce novel method scoring spinal cord histological sections show differences disease severity cnr1 wt mice eae results clinical scores cnr1 eae wt eae mice showed severe disease progression cnr1 mice confirmed using new histological scoring method peripheral immune system ifn production restimulated splenocytes cnr1 eae mice compared wt eae mice increased primary source ifn cd3 cell population however ifn production cnr1 splenocytes decreased compared wt splenocytes primary source ifn cd3+ t cells cultures naive mice stimulated either anticd3 anticd28 antibodies staphylococcal superantigens conclusion findings suggest duality cb1 receptors effects peripheral immune response varies based specific cell types stimulated knowledge complex nature receptor important part determining potential usefulness therapeutic target findings define role cb1 ifn responsespmid33998867 doi101089 can20200046,0.0
clinical course central nervous system demyelinating neurological adverse events associated antitnf therapy j neurol 2021 feb 20 doi 101007 s00415021104606 online ahead printabstractprevious studies reported association antitumor necrosis factor alpha antitnf treatment central nervous system cns events described eight patients presenting demyelinating cns events treatment antitnf autoimmune diseases followed medium period 4 years four patients presented isolated demyelinating events three patients fulfilled criteria multiple sclerosis ms one patient showed worsening preexisting ms antitnf therapy initiation patients except one showed good mediumterm prognosis observation supports association antitnf treatment demyelinating events suggests prompt discontinuation drug may lead favorable demyelinating disease outcomepmid33611609 doi101007 s00415021104606,1.0
common active inflammation progressive multiple sclerosis nat rev neurol 2021 may 25 doi 101038 s41582021005184 online ahead printno abstractpmid34035504 doi101038 s41582021005184,0.0
bee venomderived bbb shuttle correlation oligodendrocyte proliferation markers mice model multiple sclerosis neurotox res 2021 apr 19 doi 101007 s1264002100361x online ahead printabstractmultiple sclerosis chronic demyelinating disease functional disturbance immune system axonal damages shown apamin bloodbrain barrier shuttle acts ca2+ activated k+ channels sk channels blocker study effects apamin oligodendrocyte differentiation markers evaluated induced model ms briefly c57bl 6 male mice 22 5 g except control group fed 02 w w cuprizone pellets 6 weeks cuprizone withdrawal mice divided randomly six groups apamin 100 g kg bw administered intraperitoneally cotreatment phase demyelination posttreatment phase ii remyelination twice week mice anesthetized perfused phosphatebuffered saline fixed brains coronally sectioned changes oligodendrocytes markers olig2 pdgfr brdu incorporation assessed immunohistochemistry assay apamin administration increased olig2+ cells phase compared control group p 00001 also decreasing trend pdgfra+ cells observed cuprizone withdrawal p 0001 5bromo2deoxyuridine brdu incorporation test confirmed stimulation oligodendrocyte progenitor cell proliferation phase apamin exposed group p 00001 especially subventricular zone study highlights potential therapeutic effects apamin bee venomderived peptide oligodendrocyte precursor proliferation elevation myelin content oxidative induced multiple sclerosis model due cuprizone exposurepmid33871814 doi101007 s1264002100361x,1.0
novel multisystem proteinopathy caused missense anxa11 variant ann neurol 2021 may 28 doi 101002 ana26136 online ahead printabstractobjective protein misfolding plays central role amyotrophic lateral sclerosis als also conditions frontemporal dementia ftd inclusion body myopathy hibm pagets disease bone concept multisystem proteinopathies msp created account rare families segregate least 2 4 conditions pedigree calciumdependent phospholipidbinding protein annexin a11 recently associated als european pedigrees herein describe detail 3 brazilian families presenting hibm isolated combination als ftd caused novel pd40y change gene encoding annexin a11 anxa11 methods collected clinical genetic pathological skeletal muscle imaging 11 affected subjects neuroimaging also obtained 8 patients 8 matched controlsresults clinicoradiological phenotype novel hibm reveals slowly progressive predominant limbgirdle syndrome frequent axial ptosis dropped head distal medial gastrocnemius involvement well muscle pathology identified numerous rimmed vacuoles positive annexin a11 tdp43 p62 inclusions inflammation central nervous system also involved two patients ftd diffusion tensor imaging uncovered multiple areas cerebral white matter damage whole group including corticospinal tracts frontal subcortical regions interpretation findings expand phenotypic spectrum related anxa11 gene considered cause novel multisystem proteinopathy msp type 6 rather just als article protected copyright rights reservedpmid34048612 doi101002 ana26136,0.0
effects transcranial direct current stimulation cognitive dysfunction multiple sclerosis neurophysiol clin 2021 jun 1s09877053 21 000678 doi 101016 jneucli202105003 online ahead printabstractbackground around 4070 patients multiple sclerosis ms may experience cognitive impairments course disease detrimental effects social occupational activities transcranial direct current stimulation tdcs investigated pain fatigue mood disorders related ms date studies examined effects tdcs cognitive performance msobjective current study aimed investigate effects multisession tdcs protocol cognitive performance restingstate brain electrical activities patients msmethods twentyfour eligible ms patients randomly assigned real anodal sham tdcs groups 8 consecutive daily tdcs sessions left dorsolateral prefrontal cortex dlpfc patients cognitive performance assessed using cambridge brain sciencescognitive platform cbscp cortical electrical activity also evaluated using quantitative electroencephalography qeeg analysis baseline interventionresults compared sham condition significant improvement reasoning executive functions patients real tdcs group observed attention also improved considerably statistically significantly following real tdcs however significant changes restingstate brain activities observed stimulation either groupconclusion anodal tdcs left dlpfc appears promising therapeutic option cognitive dysfunction patients ms larger studies required confirm findings investigate underlying neuronal mechanismspmid34088588 doi101016 jneucli202105003,0.0
remyelination therapies multiple sclerosis optimizing translation animal models clinical trials expert opin investig drugs 2021 jun 14 doi 101080 1354378420211942840 online ahead printabstractintroduction multiple sclerosis ms common inflammatory disease central nervous system cns demyelination main pathology ms contributes clinical symptoms longterm neurological deficits left untreated remyelination natural repair damaged myelin cells oligodendrocyte lineage occurs ms eventually fails patients age encouraging timely remyelination can restore axon conduction minimize deficitsareas covered discuss correlate human ms pathology animal models propose methods deplete resident oligodendrocyte progenitor cells opcs determine whether mature oligodendrocytes support remyelination review remyelinating agents mechanisms action available clinical trial dataexpert opinion heterogeneity human ms may limit successful translation many candidate remyelinating agents patients lack biologic targets necessary leverage current approaches development therapeutics remyelination concentrated almost exclusively mobilization innate opcs however mature oligodendrocytes appear important contributor remyelination humans limiting contribution opc mediated repair models ms allow evaluation remyelinationpromoting agents mature oligodendrocytes among remyelinating reagents reviewed rhigm22 targets opcs mature oligodendrocytespmid34126015 doi101080 1354378420211942840,1.0
immunemediated diseases thromboembolic events modified delphi panel curr med res opin 2021 may 261 doi 101080 0300799520211932450 online ahead printabstractintroduction multidisciplinary panel physicians convened gain understanding relationship thromboembolic events tes immunemediated diseases imds primary objective panel assess areas consensus imd prone te well modifiable unmodifiable factors might exacerbate mitigate risk tesmethods thirteen nationally recognized physicians selected based contributions guidelines publications patient care modified delphi panel consisted four rounds engagement 1 semistructured interview 2 expert panel questionnaire 3 inperson panel discussion 4 consensus statement surveyresults ulcerative colitis crohns disease identified two four imds highest te risk consensus reached several nonmodifiable modifiable characteristics highrisk approaches reduce te incidence identified altering treatment requiring monitoring patients tes modifying patient behaviors janus kinase inhibitors corticosteroids identified therapies required evaluation given potential te riskdiscussion panel reached consensus several imds elevated risk tes physicians unable control patient level risk factors can control therapies used consequently physicians consider specific imd aware te risk factors take account risk factors selecting therapies optimally manage conditions reduce risk tes populationpmid34034599 doi101080 0300799520211932450,0.0
innate immune response characterizes posterior reversible encephalopathy syndrome j clin immunol 2021 apr 12 doi 101007 s10875021010333 online ahead printabstractwhile posterior reversible encephalopathy syndrome pres often characterized inflammatory cerebrospinalfluid csf profile knowledge immune cell patterns pres lacking thus retrospectively characterized csf peripheral blood pb 15 pres patients analyzed multidimensional flow cytometry fc results compared 72 controls well 9 patients progressive multifocal leukoencephalopathy pml relevant differential diagnosis 15 multiple sclerosis patients ms classical neuroinflammatory disorder respectively total protein level csf pres patients elevated compared controls ms pml indepth fc analysis revealed differences adaptive immune cells b cells plasma cells cd4+ cd8+ t cells pb csf pres compared controls contrast observed alterations adaptive immune response csf pml ms compared pres indicating adaptive immune response driver disease pres indeed pres characterized innate immune response cd14++ cd16+ intermediate monocytes elevated pb csf cd14++ cd16 classical monocytes decreased pb pres patients compared controls levels cd14++ cd16+ monocytes correlated duration hospital stay surrogate marker disease severity pres patients findings argue role innate rather adaptive immunity pathophysiology pres observed shift monocyte subsets might provide valuable diagnostic clues clinical management patientspmid33844127 doi101007 s10875021010333,0.0
neurofilament light chain marker cortical atrophy multiple sclerosis without radiological signs disease activity j intern med 2021 apr 19 doi 101111 joim13286 online ahead printno abstractpmid33871105 doi101111 joim13286,0.0
drives differences preferences health states patients public qualitative investigation respondents#39 thought processes soc sci med 2021 jun 18 282114150 doi 101016 jsocscimed2021114150 online ahead printabstractcosteffectiveness analyses using qualityadjusted lifeyears qalys used decisionmaking regarding interventions available via many national healthcare systems qalys calculated based health state values provided preference elicitation techniques several national decisionmaking bodies recommend health state values based preferences elicited general populations rather patients previous studies shown systematic differences health state values elicited members general population patients various explanations phenomenon proposed however empirical evidence scarce aimed explore possible reasons discrepancies public patient valuations undertaking qualitative cognitive interviews asking 14 members general population 12 people multiple sclerosis ms think aloud completing preference elicitation task time tradeoff msrelated health states interviews undertaken december 2016 october 2017 south west region england analysed using framework method anticipated found participants ms experience health problems used experience consider might adapt health states time dimensions healthrelated quality life important found evidence participants ms less affected framing effects focusing illusions likely prioritise nonphysical dimensions health prone loss aversion endowment effects noncompensatory decisionmaking findings contribute understanding patients members general population respond preference elicitation exercises preferences may differ may help inform developing areas research joint presentation costeffectiveness results multiple perspectives use preferences elicited patients experienced health statespmid34171703 doi101016 jsocscimed2021114150,0.0
classification criteria multiple sclerosisassociated intermediate uveitis multiple sclerosis uveitis j ophthalmol 2021 apr 9s00029394 21 001690 doi 101016 jajo202103044 online ahead printabstractpurpose determine classification criteria multiple sclerosisassociated intermediate uveitisdesign machine learning cases multiple sclerosisassociated intermediate uveitis 4 intermediate uveitidesmethods cases intermediate uveitides collected informaticsdesigned preliminary database final database constructed cases achieving supermajority agreement diagnosis using formal consensus techniques cases split training set validation set machine learning using multinomial logistic regression used training set determine parsimonious set criteria minimized misclassification rate among intermediate uveitides resulting criteria evaluated validation setresults five hundred eightynine cases intermediate uveitides including 112 cases multiple sclerosisassociated intermediate uveitis evaluated machine learning overall accuracy intermediate uveitides 998 training set 993 validation set 95 confidence interval 961 999 key criteria multiple sclerosisassociated intermediate uveitis included unilateral bilateral intermediate uveitis diagnosis multiple sclerosis mcdonald criteria key exclusions included syphilis sarcoidosis misclassification rates multiple sclerosisassociated intermediate uveitis 0 training set 0 validation set respectivelyconclusions criteria multiple sclerosisassociated intermediate uveitis low misclassification rate appeared perform sufficiently well enough use clinical translational researchpmid33845022 doi101016 jajo202103044,0.0
multiple sclerosis switching natalizumab highefficacy treatments mitigate progressive multifocal leukoencephalopathy risk neurotherapeutics 2021 sep 3 doi 101007 s1331102101102w online ahead printno abstractpmid34480292 doi101007 s1331102101102w,0.0
corticosubcortical functional connectivity modifications fatigued ms patients treated fampridine amantadine eur j neurol 2021 apr 14 doi 101111 ene14867 online ahead printabstractbackground fatigue multiple sclerosis ms common disabling medication efficacy still fully proven aim study investigate fourweek modifications fatigue severity 45 relapsingremitting ms patients following different symptomatic treatments concomitant resting state rs functional connectivity fc changesmethods patients randomly blindly assigned treatment fampridine n15 amantadine n15 placebo n15 underwent clinical 3t rs fmri baseline t0 four weeks w4 treatment fifteen healthy controls hc also studied changes modified fatigue impact scale mfis network rs fc assessedresults ms abnormalities network rs fc t0 differ treatment groups correlated fatigue severity w4 global subscore mfiss decreased groups timebytreatment interaction w4 patient groups changes rs fc several networks significant timebytreatment interactions basal ganglia sensorimotor defaultmode networks fampridine patients vs groups frontoparietal network amantadine patients fampridinegroup rs fc changes correlated concurrently decreased mfis r range075 074 p range0003005 conclusions fatigue improved ms groups independently treatment concomitant rs fc modifications located sensorimotor inferior frontal subcortical regions fampridine amantadine patients associative sensory cortices placebo patientspmid33852752 doi101111 ene14867,0.0
characterization chronic active multiple sclerosis lesions sodium 23 na mri preliminary observations eur j neurol 2021 apr 17 doi 101111 ene14873 online ahead printabstractbackground increasing interest chronic active multiple sclerosis ms lesions new magnetic resonance imaging mri marker disease progression chronic active lesions characterized progressive tissue matrix damage axonal loss chronic inflammation sodium 23 na mri provides biochemical marker cell integrity tissue viability quantitative manner aim study investigate 23 na mri tissue abnormalities chronic active lesions indicators tissue destructionmethods identify chronic active lesions two 3d magnetizationprepared rapid acquisition gradientecho mprage datasets obtained 12 months apart processed using voxelguided morphometry vgm algorithm crosssectional 23 na mri performed 12month followup period total sodium concentration tsc calculated chronic active lesions compared shrinking chronic stable acute contrastenhancing lesionsresults overall 70 ms lesions 21 chronic active 10 shrinking 29 chronic stable lesions 10 acute contrastenhancing lesions twelve patients included tsc chronic active 4957 847 mm significantly higher shrinking 4216 39 mm p 003 chronic stable lesions 3992 482 mm p 0001 chronic active lesions showed similar sodium values compared acute contrastenhancing lesions 4806 665 mm p 097 differences shrinking chronic stable lesions observed p 089 conclusion high sodium values chronic active ms lesions may indicator ongoing inflammation tissue damagepmid33864730 doi101111 ene14873,0.0
visual dysfunction multiple sclerosis animal model experimental autoimmune encephalomyelitis review mol neurobiol 2021 mar 20 doi 101007 s12035021023554 online ahead printabstractvisual disabilities central nervous system autoimmune diseases multiple sclerosis ms animal model experimental autoimmune encephalomyelitis eae important symptoms past studies focused neuroinflammatory changes demyelination white matter brain spinal cord ms neuroinflammatory lesions diagnosed visual pathway lesions may perturb visual function similarly neuropathological changes retina optic nerves found animals chronic eae although retina optic nerves immunologically privileged sites via bloodretina barrier bloodbrain barrier respectively inflammation can occur via routes uvea eg iris choroid cerebrospinal fluid meninges review primarily addresses direct involvement bloodretina barrier bloodbrain barrier development retinitis optic neuritis eae models additional routes including proinflammatory mediatorfilled choroidal subarachnoid spaces also discussed respect roles eaeinduced visual disability analogues ms humanspmid33745114 doi101007 s12035021023554,1.0
lack attention administration fampridine symptomatic drug iranian multiple sclerosis patients iran j public health 2021 jul 50 7 15131514 doi 1018502 ijphv50i76654no abstractpmid34568200 pmcpmc8426761 doi1018502 ijphv50i76654,0.0
cd4+ cd25+ t cell response shorttime interferonbeta therapy il10 il23a foxp3 genes multiple sclerosis patients int j clin pract 2021 apr 22e14238 doi 101111 ijcp14238 online ahead printabstractaim study interferonbeta ifn multiple sclerosis ms drug years therapeutic effects patient yet considerable portion experienced therapeutic response ifn therefore necessary determine diseasespecific biomarkers affect drug response aimed determine effects interleukin 10 il10 23 il23a well forkhead box p3 foxp3 genes ms ifn therapymaterials methods peripheral blood mononuclear cells pbmcs fortytwo ms patients isolated obtain cd4+ cd25+ t cells cell types characterized flow cytometry determine optimum drug concentration ifn cytotoxicity assays assessed cell type 4 16 24 48 hours respectively cells cultured presence 500 iu ml ifn cdna synthesis performed mrna extraction rtpcr performed measure gene expressions il10 il23a foxp3 results evaluated statisticallyresults found cytotoxic effect ifn efficient exposure time expanded regardless drug concentration moreover cd25+ t lymphocytes resistant ifn il23a downregulated whereas foxp3 upregulated 48h cd4+ t cells cd25+ t cells graded increase foxp3 obtained il10 expression gradually decreased throughout drug intakeconclusion although considerable change expression obtained longterm ifn effect genes cells determined followup least yearpmid33884734 doi101111 ijcp14238,0.0
elevated chemokines cytokines eosinophils neuromyelitis optica spectrum disorders mult scler relat disord 2021 apr 9 52102940 doi 101016 jmsard2021102940 online ahead printabstractbackground eosinophil infiltration one distinctive features neuromyelitis optica spectrum disorders nmosd demyelinating diseases including multiple sclerosis ms eosinophils express chemokine receptor ccr3 activated eotaxins eotaxin1 2 3 monocyte chemoattractant protein mcp 4 aimed investigate role mcps mcp1 2 3 4 eotaxins acute phase nmosdmethods levels serum cerebrospinal fluid csf eotaxins mcps interleukin il 5 tumor necrosis factor tnf granulocytemacrophage colonystimulating factor gmcsf il6 measured using cytokine multiplex assay 26 patients nmosd 13 immunotherapy 13 without immunotherapy 9 patients ms 9 patients noninflammatory neurological diseases ond glial fibrillary acidic protein assessed using elisaresults serum mcp1 csf mcp2 levels significantly higher patients nmosd ond moreover serum mcp4 csf eotaxin2 3 levels significantly higher nmosd patients compared ms ond serum mcp1 4 csf eotaxin2 3 levels significantly correlated expanded disability status scale nmosd tnf gmcsf stimulate chemokines higher patients nmosd ond moreover serum mcp1 4 significantly increased il5 gmcsf stimulation tnf il6 csf eotaxin2 significantly increased gmcsf significant differences serum mcp1 4 levels nmosd patients without immunotherapyconclusion findings suggest elevated serum mcp1 4 csf eotaxin2 3 may key step eosinophil recruitment acute phase nmosdpmid33930716 doi101016 jmsard2021102940,1.0
learningdependent dendritic spine plasticity impaired spontaneous autoimmune encephalomyelitis dev neurobiol 2021 may 4 doi 101002 dneu22827 online ahead printabstractcognitive impairment often observed multiple sclerosis animal models experimental autoimmune encephalomyelitis eae using mice immunizationinduced eae previously shown stability cortical synapses markedly decreased clinical onset eae study examined learningdependent structural synaptic plasticity spontaneous eae model transgenic mice expressing myelin basic proteinspecific t cell receptor genes develop eae spontaneously around 8 weeks age using vivo twophoton microscopy found elimination formation rates postsynaptic dendritic spines somatosensory motor cortices increased weeks detectable signs eae remained high disease onset despite elevated basal spine turnover motor learninginduced spine formation reduced presymptomatic eae mice line impaired ability retain learned motor skills additionally found substantial elevation ifn mrna brain 4weekold presymptomatic mice treatment antiifn antibody reduced dendritic spine elimination cortex together findings reveal synaptic instability failure form new synapses learning early brain pathology eae may contribute cognitive behavioral deficits seen autoimmune diseasespmid33949123 doi101002 dneu22827,1.0
new autoimmune diseases autologous hematopoietic stem cell transplantation multiple sclerosis bone marrow transplant 2021 apr 28 doi 101038 s4140902101277y online ahead printabstractsecondary autoimmune diseases 2ndads frequently autoimmune cytopenias aics first described allogeneic hematopoietic stem cell transplantation hsct undertaken malignant hematological indications occurred prevalence 565 attributed allogeneic immune imbalances context graft versus host disease viral infections chronic immunosuppression subsequently 2ndads reported complicate roughly 214 autologous hscts performed autoimmune disease alemtuzumab conditioning regimen identified risk development 2ndads either allogeneic autologous hsct consistent high rates 2ndads using alemtuzumab monotherapy due significant consequences variable incidence depending conditioning regimen 2ndads similarity known immune reconstitution kinetics autologous hsct autoimmune diseases alemtuzumab monotherapy propose imbalance b t lineage regeneration early hsct may underlie pathogenesis 2ndadspmid33911200 doi101038 s4140902101277y,0.0
18year temporal trend fiveyear projection multiple sclerosis southern iran mult scler relat disord 2021 may 8 52103018 doi 101016 jmsard2021103018 online ahead printabstractbackground multiple sclerosis ms imposes significant burdens patients families national healthcare systems particularly resource constraint proper prioritization resource allocation therefore essential effective disease management accordingly sought assess temporal profile ms incidence past two decades southeast iranmethods longitudinal design employed using data iranian multiple sclerosis registry system march 2001 march 2019 n6034 annual agestandardized incidence rates ms cases clinically isolated syndrome also included calculated trend incidence 2001 2018 analyzedresults ageadjusted incidence rate ms raised 172 100 000 2001 1129 100 000 2018 average 18year incidence rate 630 100 000 indicating notable rise incidence ms pvalue0001 however female male ratio 362 remained relatively stable study periodconclusion study suggests fars province incidence ms remarkably rising past two decades recommend studies better understand determinants pattern implementing effective policies lowering burden ms another important step regardpmid34023774 doi101016 jmsard2021103018,0.0
persons suspicious onset multiple sclerosis undetermined diagnosis persistent lower cognition reduced quality life mult scler relat disord 2021 apr 24 52102977 doi 101016 jmsard2021102977 online ahead printabstractbackgound differential diagnosis multiple sclerosis ms includes variety disorders misdiagnosis commonobjective followup persons suspected onset ms diagnostic investigation negativemethods prospective study including 271 persons clinical features suspected ms onset 136 persons diagnosed ms clinically isolated syndrome pwms 46 disorders 89 persons negative diagnostic workup ie persons undetermined diagnosis pwud underwent diagnostic reassessment remained without diagnosis investigated signs pathology including cognitive tests assessments quality life qol results compared pwms 24 age sex matched healthy controls hc results reassement 55 20 persons still undetermined diagnosis pwud similar age gender distribution pwms 76 pwud suspected clinical onset included sensory symptoms pwud pwms scored similarly cognitive tests qol significantly lower hc 3 years followup pwms pwud improved test parameters pwud scored lower pwms cognitionconclusion pwud constituted dominating differential diagnosis persons suspected clinical onset ms qol cognition comparable pwms significantly lower hcpmid33964570 doi101016 jmsard2021102977,0.0
cumulative effects therapies disability relapsing multiple sclerosis abstractbackgroundlongterm effectiveness treatment remains key question multiple sclerosis ms cumulative effects past treatment investigated farobjectiveexplore relationship treatment exposure disability risk patients relapsingremitting multiple sclerosis rrms methodsa total 2285 adult patients french nationwide cohort included outcomes irreversible edss4 conversion secondary progression multiple sclerosis spms associations treatments risk disability assessed using novel weighted cumulative exposure model assuming 3year lag account reverse causality flexible approach accounts past exposure multivariate cox proportional hazards model computing weight functionresultsat baseline mean standard deviation age patients 334 89years 750 women 15year continuous treatment starting 20years ago associated decrease risk 26 irreversible edss4 34 spms compared 5year treatment starting 10years ago risk disability decreased increasing duration exposure diseasemodifying treatment dmt conclusionlongterm use treatments rrms stronger beneficial cumulative impact early uses delays occurrence moderate disability conversion spms,1.0
epidemiology multiple sclerosis lebanon rising prevalence middle east mult scler relat disord 2021 apr 20 52102963 doi 101016 jmsard2021102963 online ahead printabstractbackground epidemiology multiple sclerosis ms studied many countries middle east prevalence incidence ms lebanon still unknownobjectives determine incidence prevalence ms lebanonmethods lebanese patients diagnosed ms january 2018 december 2018 identified using database governmental thirdparty payers crude age sexspecific 2018 prevalence incidence among lebanese patients calculatedresults 2248 ms patients identified 671 women female male ratio 21 mean age 418 1296 years 2018 prevalence ms 6291 cases per 100 000 persons 95 ci 6041 6541 overall incidence ms lebanon 836 cases per 100 000 95 ci 745 927 mean age onset 345 125 yearsconclusion first study assess prevalence incidence ms lebanon confirming lebanon moderate highrisk area ms high rates commensurate recently published studies middle east pointing significant rise incidence prevalence disease regionpmid33934011 doi101016 jmsard2021102963,0.0
longitudinal analysis disability outcomes among young people ms mult scler relat disord 2021 apr 20 52102966 doi 101016 jmsard2021102966 online ahead printabstractbackground age onset ms appears influence course disease progression people younger age onset might different disability trajectoryobjectives identify longitudinal patterns disability progression measured changes multiple sclerosis functional composite msfc young people ms drug trials estimate extent disability progression differ two age groups 25 years 26 35 years methods data multiple sclerosis outcomes assessment consortium msoac used longitudinal patterns msfc identified using groupbased trajectory models gbtm difference expected observed proportions people pediatriconset ms chisquare statistic used linear mixed models used estimate average change performance time age sexresults gbtm results showed little variability performance time mixed modeling showed younger group performed better gait speed dexterity cognition men performed poorer dexterity cognition distribution people pediatriconset ms differed expected dexterity cognition edssconclusions combined use trajectory models linear mixed models provided rich information variability function timepmid33934012 doi101016 jmsard2021102966,0.0
evidence synergism among three genetic variants patient lmnarelated lipodystrophy amyotrophic lateral sclerosis leading remarkable nuclear phenotype mol cell biochem 2021 mar 4 doi 101007 s11010021041037 online ahead printabstractneurodegenerative diseases including amyotrophic lateral sclerosis als can clinically heterogeneous may explained coinheritance multiple genetic variants modify clinical course study examine variants three genes family one individual presenting als lipodystrophy sequencing revealed pgly602ser variant lmna two additional variants one setx gintron1013delctt fus pgly167_gly168del latter genes linked als family members genotyped variant combination variants detected functionally evaluated vitro regarding effects cell survival expression patterns cellular phenotype muscle biopsy retrieved individual als showed leakage chromatin nucleus phenotype recapitulated vitro expression three variants simultaneously individually expressed variants gave cellular phenotypes unremarkable interestingly fus variant appears protective effects setx lmna variants cell viability may indicate loss interaction fus setx rloops conclude findings support genetic modifications explanation clinical heterogeneity observed human diseasepmid33661429 doi101007 s11010021041037,0.0
vitamin d diseasemodifying therapy multiple sclerosis expert rev clin immunol 2021 apr 9 doi 101080 1744666x20211915772 online ahead printno abstractpmid33836645 doi101080 1744666x20211915772,0.0
msprodiscuss development digital anamnesis tool identify disease progression multiple sclerosis fortschr neurol psychiatr 2021 mar 15 doi 101055 a13976851 online ahead printabstractduring course multiple sclerosis ms patients relapsing remitting ms rrms convert secondary progressive ms spms msphenotype associated steady deterioration functional ability independent relapses worsened prognosis due heterogeneity conversion spmsdiagnosis often challenging made retrospectively delay several years review first discuss advantages limitations screening tools early spmsdetection spms nomogram ms prediction score best spms definition approach screening tools might help shorten phase diagnostic uncertainty focus development msprodiscuss novel webbased tool helps treating neurologist systematically assesses parameters highly relevant spmsconversion routine anamnesis parameters involve disease activity symptoms impacts patients overall symptoms recent validation study msprodiscuss demonstrated high sensitivity specificity interrater reliability msprodiscuss impose additional time burden treating neurologist results easy interpret simple traffic light system first usability tests therefore assessed helpful tool clinical routine early detection clinically significant progression diagnostic tools msprodiscuss open timewindow therapeutic interventionspmid33723837 doi101055 a13976851,0.0
multiple sclerosislike nmosd patients suffer severe worsening status fingolimod initiation mult scler relat disord 2021 apr 24 52102975 doi 101016 jmsard2021102975 online ahead printabstractbackground initial clinical manifestations nmosd may rarely overlap ms fingolimod may trigger severe attacks patients nmosd previously misdiagnosed ms cases rare pathophysiology remains elusivemethods recruited nmosd patients treated fingolimod singlecenter cohort afrocaribbean neuroinflammatory patients fortdefrance french west indies six patients collected literatureresults among 622 patients followed locally ms 101 received fingolimod two suffered severe attacks revealing typical nmosd presentation two patients found aqp4igg risk misdiagnosed nmosd ms highrisk afrocaribbean patients estimated 19 0 47 among whole cohort relapses occurred within month fingolimod initiation five patients attacks severe contrasted previously benign attacks suggesting shift severe disorder unusual finding patients large brain lesionsconclusion aqp4igg obtained initiation fingolimod highrisk patients especially areas high nmosd prevalencepmid33951589 doi101016 jmsard2021102975,0.0
understanding managing impact covid19 pandemic lockdown patients multiple sclerosis expert rev neurother 2021 jul 17 doi 101080 1473717520211957673 online ahead printabstractintroduction covid19 sweeping world year people multiple sclerosis ms might particularly vulnerable either disease iteself ongoing immune treatment aim review understand impact covid19 pandemic lockdown patients ms provide evidencebased advice ensure high standard care even pandemicareas covered literature search conducted scopus web science pubmed electronic databases articles reference lists investigate effect covid19 ms patients treatment access healthcare services mentalhealththe search terms multiple sclerosis covid19 combined following term disease modifying treatment steroids vaccination mental health stress quality life management impact recommendationsexpert opinion ensure ms control pandemic minimizing risk covid19 contagion facetoface visits may implemented televisits management relapses dmts schedule adapted based specific benefit risk ratio patient considering disease activity disability comorbidities vaccination strongly recommended telerehabilitation online psychological support programs encouraged preserve motor performances mental healthpmid34278928 doi101080 1473717520211957673,0.0
can coronavirus disease 2019 covid19 trigger exacerbation multiple sclerosis retrospective study mult scler relat disord 2021 apr 11 52102947 doi 101016 jmsard2021102947 online ahead printabstractthe effect coronavirus disease covid19 risk relapse multiple sclerosis ms unknown retrospective study 41 relapsingremitting ms patients number relapses predefined riskperiod arp compared previous two years previous two years total 32 attacks reported 5 156 atrisk period adjusting age sex increased risk attack arp compared previous two years rr 2566 95ci 10756124 p0034 preliminary study suggested covid19 can trigger exacerbation mspmid33979771 doi101016 jmsard2021102947,0.0
extracellular vesicles treatment central nervous system diseases adv drug deliv rev 2021 may 12s0169409x 21 001629 doi 101016 jaddr202105006 online ahead printabstractthe interest extracellular vesicles evs increased last decade now established vesicles play role pathogenesis central nervous system diseases cns explains studied biomarkers pathologies hand evs can also present therapeutic properties often similar parent cells observed mesenchymal stem cellderived evs can used therapeutics alone combined bioactive molecule treatment cns diseases can cross bloodbrain barrier easily synthetic nanomedicines less immunogenic clinical trials currently ongoing still challenges overcome clinical translation scaleup production lack standardization isolation characterization methods low encapsulation efficiencypmid33991589 doi101016 jaddr202105006,0.0
improvement previous decades time diagnosis time initiating dmd ms patients argentina mult scler relat disord 2021 may 7 52103007 doi 101016 jmsard2021103007 online ahead printabstractbackground objective study compare interval first symptom ms diagnosis interval date diagnosis dmd initiation introduction upgraded ms diagnosis criteriamethods retrospective cohort study included data concerning date disease onset first relapse date diagnosis confirmed disease date dmd initiation available kaplanmeier estimator plots applied survival probabilities evaluated 2 diagnosis epoch groups according diagnostic criteria advised time group 1 diagnosis performed 20052009 2005 revised mcdonald criteria group 2 diagnosis performed 20102017 2010 revised mcdonald criteria results 654 patients included 278 group 1 308 group 2 mean time disease onset diagnosis group 1 11 4 vs 7 3 months p 0001 mean time disease diagnosis first dmd 29 11 months group 1 vs 68 15 months group 2 p 0002 conclusion although shortening time diagnosis described trend increase time initiate dmd noted group 2pmid34000685 doi101016 jmsard2021103007,0.0
atlas mitochondrial dna genotypephenotype associations uk biobank nat genet 2021 may 17 doi 101038 s41588021008681 online ahead printabstractmitochondrial dna mtdna variation common diseases underexplored partly due lack genotype calling qualitycontrol procedures developing atscale workflow mtdna variant analyses show correlations nuclear mitochondrial genomic structures within subpopulations great britain establish uk biobank reference atlas mtdnaphenotype associations total 260 mtdnaphenotype associations new p 1 105 including rs2853822 m8655 ct mtatp6 type 2 diabetes rs878966690 m13117 ag mtnd5 multiple sclerosis 6 mtdna associations adult height 24 mtdna associations 2 liver biomarkers 16 mtdna associations parameters renal function rarevariant genebased tests implicated complex genes modulating mean corpuscular volume mean corpuscular hemoglobin seven traits rare common mtdna associations rare variants tended larger effects common variants work illustrates value studying mtdna variants common complex diseases lays foundations future largescale mtdna association studiespmid34002094 doi101038 s41588021008681,0.0
covid19 associated new symptoms multiple sclerosis prevented disease modifying therapies mult scler relat disord 2021 may 5 52102939 doi 101016 jmsard2021102939 online ahead printabstractbackground infections can trigger exacerbations multiple sclerosis ms effects coronavirus disease 2019 covid19 ms known aim study understand impact covid19 new preexisting symptoms msmethods covid19 ms study ongoing communitybased prospective cohort study conducted part united kingdom ms register people ms covid19 invited email complete questionnaire ms symptoms infection ms exacerbation defined developing new ms symptoms worsening preexisting ms symptomsresults fiftyseven percent 230 404 participants ms exacerbation infection 82 developed new ms symptoms 207 experienced worsened preexisting ms symptoms 59 reported disease modifying therapies dmts reduced likelihood developing new ms symptoms infection 0556 95ci 03160978 participants higher precovid19 webedss webbased expanded disability status scale score 1251 95ci 10601478 longer ms duration 1042 95ci 10091076 likely experience worsening preexisting ms symptoms infectionconclusion covid19 infection associated exacerbation ms dmts reduced chance developing new ms symptoms infectionpmid34010764 doi101016 jmsard2021102939,0.0
plasma thiol disulphide homeostasis changes patients relapsingremitting multiple sclerosis int j clin pract 2021 apr 23e14241 doi 101111 ijcp14241 online ahead printabstractbackground multiple sclerosis ms neuroinflammatory disease inflammation oxidative stress play important roles pathology thiol disulphide homeostasis tdh special oxidative stress biomarker found affected several disorders including ms study demonstrating effects attack status relapsingremitting multiple sclerosis rrms patients tdh levels aim determine tdh levels three different periods rrms patients healthy individualsmethods study carried 29 patients rrms without prior attack last twelve months ms control 21 rrms patients clinical acute attack within last week ms relapse 12 21 ms relapse patients one month onset attack following 1000 mg methylprednisolone 7 days ms remission 30 age sexmatched healthy individuals tdh status determined using automated spectrophotometric analysis method tdh levels patient groups control subjects compared otherresults lowest native thiol total thiol levels native thiol total thiol ratio found ms relapse patients comparison ms control ms remission groups healthy controls contrast disulphide levels disulphide native thiol disulphide total thiol ratios highest ms relapse group compared patient groups healthy subjectsconclusion findings indicate increased oxidative stress rrms patients reflected decreased native total thiol increased disulphide levels since formation disulphide bonds reversible progression rrms involving abnormal tdh may controlled converting disulphides thiols suggest determining dynamic tdh status novel special biomarker diagnosis prognosis rrms patientspmid33891773 doi101111 ijcp14241,0.0
picture worth thousand words using photoelicitation study body image middletoolder age women without multiple sclerosis qual health res 2021 may 2410497323211014830 doi 101177 10497323211014830 online ahead printabstractin study explored women varying relationships disability aging used photographs represent body image experiences seven middleaged older adult women without multiple sclerosis asked provide 10 photographs represented body image complete oneonone interview used reflexive thematic analysis develop themes interpret findings overall women expressed complicated relationships bodies represented symbolism scrutiny body features eg posture varicose veins arthritis also deep reflection linked positive body image resilience findings revealed nuanced experiences women aging disability gender also commonly experienced ingrained views body appearance participant illustrated difficult negotiation aesthetic dimension body image finally provide important implications use visual methods body image researchpmid34027715 doi101177 10497323211014830,0.0
focal white matter lesions induce longlasting axonal degeneration neuroinflammation behavioral deficits neurobiol dis 2021 apr 28105371 doi 101016 jnbd2021105371 online ahead printabstractmultiple sclerosis ms chronic inflammatory disease central nervous system cns episodes inflammatory demyelination remyelination remyelination linked functional recovery ms patients evidence ongoing tissue damage despite complete myelin repair study investigated longterm consequences acute demyelinating white matter cns lesion purpose acute demyelination induced 5weekcuprizone intoxication male c57bl 6 j mice tissues examined 7month recovery period myelination oligodendrocyte densities appeared normal ongoing axonal degeneration glia cell activation found remyelinated corpus callosum neuropathologies paralleled subtle gait abnormalities evaluated using digigait high speed ventral plane videography gene array analyses revealed increased expression levels various inflammation related genes among protein kinase c delta prkcd immunofluorescence stains revealed predominant microglia macrophages prkcd expression cuprizone tissues postmortem ms lesions results support hypothesis chronic microglia macrophages driven tissue injury represents key aspect progressive neurodegeneration functional decline mspmid33932559 doi101016 jnbd2021105371,1.0
softseg advantages soft versus binary training image segmentation med image anal 2021 mar 18 71102038 doi 101016 jmedia2021102038 online ahead printabstractmost image segmentation algorithms trained binary masks formulated classification task per pixel however applications medical imaging blackandwhite approach constraining contrast two tissues often illdefined ie voxels located objects edges contain mixture tissues partial volume effect consequently assigning single hard label can result detrimental approximation instead soft prediction containing nonbinary values overcome limitation study introduce softseg deep learning training approach takes advantage soft ground truth labels bound binary predictions softseg aims solving regression instead classification problem achieved using binarization preprocessing data augmentation ii normalized relu final activation layer instead sigmoid iii regression loss function instead traditional dice loss assess impact three features three opensource mri segmentation datasets spinal cord gray matter multiple sclerosis brain lesion multimodal brain tumor segmentation challenges across multiple random dataset splittings softseg outperformed conventional approach leading increase dice score 20 gray matter dataset p0001 33 brain lesions 65 brain tumors softseg produces consistent soft predictions tissues interfaces shows increased sensitivity small objects eg multiple sclerosis lesions richness soft labels represent interexpert variability partial volume effect complement model uncertainty estimation typically unclear binary predictions developed training pipeline can easily incorporated existing deep learning architectures softseg implemented freelyavailable deep learning toolbox ivadomed https ivadomedorg pmid33784599 doi101016 jmedia2021102038,0.0
peripheral nervous system multiple sclerosisunderstanding involvement via autonomic nervous system neurol sci 2021 may 25 doi 101007 s10072021053099 online ahead printabstractaim aim review summarize clinical paraclinical findings demonstrate multiple sclerosis ms affects peripheral nervous system pns well central nervous system cns methods narrative reviewresults ms traditionally defined chronic demyelinating immunemediated disease cns however emerging evidence ms disease solely affect cns can manifest pns involvement well several pathology studies reported signs demyelination pns well structural functional involvement pns persons ms pwms functional aspect several studies shown autonomic nervous system ans involvement form sudomotor dysfunction measured quantitative sudomotor axon reflex test qsart different stages ms adding growing body evidence indicate pns involvement ms review clinical pathological neurophysiological imaging findings demonstrate ms affects pns well cns summarized emphasis ans abnormalitiesconclusion largescale research needed order fully understand frequency importance pns affection mspmid34036450 doi101007 s10072021053099,1.0
overview ocular side effect selinexor oncologist 2021 mar 16 doi 101002 onco13756 online ahead printabstractbackground purpose aim review elucidate type frequency ocular adverse events associated selinexor goal quantify occurrence events investigatorinitiated trialmethods retrospectively reviewed medical records 174 patients treated least one dose selinexor combination multiple standard chemotherapy immunotherapy agents july 2015 july 2020 comprehensive cancer center united states reported ocular adverse events assessedresults total 174 patient medical records reviewed patients received least one dose selinexor combination multiple standard chemotherapy immunotherapy agents cohort patients advanced malignancies total 34 1954 patients experienced 37 ocular adverse events frequently reported ocular symptom blurred vision reported 22 126 4 patients frequently reported treatmentrelated adverse event mild agerelated nuclear sclerosis cataract reported 29 1666 patients progression reported 7 40 patients dry eye syndrome reported 21 121 patients 19 109 diagnosed mild dry eye second none ocular adverse events required therapy discontinuation conclusion findings highlight ocular adverse events associated oral selinexor mild frequently reported ocular treatmentrelated adverse events mild dry eye progression agerelated nuclear sclerosis none ocular adverse events required therapy discontinuation implications practice patients receiving selinexor combination multiple standard chemotherapy immunotherapy agents reviewed total 34 patients experiencing 37 ocular adverse events findings highlight ocular adverse events associated oral selinexor mild frequently reported ocular treatmentrelated adverse events mild dry eye progression agerelated nuclear sclerosis none ocular adverse events required therapy discontinuationpmid33728727 doi101002 onco13756,0.0
skewing b cell receptor repertoire myalgic encephalomyelitis chronic fatigue syndrome brain behav immun 2021 mar 29s08891591 21 001537 doi 101016 jbbi202103023 online ahead printabstractmyalgic encephalomyelitis chronic fatigue syndrome cfs debilitating condition characterized fatigue postexertional malaise accompanied various signs neurological autonomic dysfunction cfs often triggered infectious episode associated aberrant immune system report cfs disorder characterized skewed b cell receptor gene usage applying nextgeneration sequencing determine clonebased ighv ighd ighj repertoires revealed biased usage several ighv genes peripheral blood b cells cfs patients results receiver operating characteristic roc analysis indicated possibility distinguishing patients healthy controls based skewed b cell repertoire meanwhile b cell clones using ighv330 ighv3303 genes frequent patients obvious infectionrelated episode onset correlated expression levels interferon response genes plasmablasts collectively results imply b cell responses cfs directed infectious agents priming antigens induced disease onsetpmid33794313 doi101016 jbbi202103023,0.0
imaging evaluation hereditary renal tumors pictorial review jpn j radiol 2021 mar 23 doi 101007 s11604021011095 online ahead printabstractmore 10 hereditary renal tumor syndromes hrtss related germline mutations reported hrtsassociated renal extrarenal manifestations benign malignant tumors radiologists play important role detecting solitary multiple renal masses without extrarenal findings imaging may raise possibility inherited predisposition renal cell carcinoma providing direction screening intervention surveillance patients close family members development potentially lethal renal extrarenal tumors renal cell carcinomas rccs associated von hippellindau disease typically slow growing rccs associated hrtss hereditary leiomyomatosis renal cell carcinoma syndrome highly aggressive therefore radiologists need familiar clinical imaging findings renal extrarenal manifestations hrtss article reviews clinical imaging findings evaluation patients wellestablished hrtss radiologists perspective facilitate clinical decisionmaking process patient managementpmid33759057 doi101007 s11604021011095,0.0
association epsteinbarr virus latently expressed genes multiple sclerosis mult scler relat disord 2021 may 7 52103008 doi 101016 jmsard2021103008 online ahead printabstractbackground despite mounting evidence supporting etiologic role epsteinbarr virus ebv multiple sclerosis ms exact mechanisms virus may contribute disease development still unknown aim study analyze seven highly polymorphic ebv latently expressed genes individuals diagnosed ms comparison healthy controls hc investigate possible association ebv variants individuals risk towards msmethods blymphocytes isolated ms patients n 30 hc n 33 isolation ebv genomic dna sanger sequencing employed analyze ebv latent gene regionsresults total 26 variants detected cohort 17 significantly associated ms group nine significantly associated hc following designation ebv alleles based variants ms risk found significantly associated presence ebna3b21 allele p 00008 lmp11 allele p 001 whereas ebna13 allele p 0005 ebna21 allele p 0001 well ebna3b22 allele p 00003 appeared provide protective roleconclusions study indicates marked association ebv genetic variants ms lending support towards possible molecular mechanisms ebv may contribute disease developmentpmid34010765 doi101016 jmsard2021103008,0.0
vaccine considerations multiple sclerosis covid19 era adv ther 2021 jun 1 doi 101007 s12325021017613 online ahead printabstractpeople multiple sclerosis ms risk infections can result amplification baseline symptoms possibly trigger clinical relapses vaccination can prevent infection activation humoral cellular immune responses particularly pertinent era emerging novel vaccines severe acute respiratory syndrome coronavirus 2 virus causes coronavirus disease 2019 covid19 ms diseasemodifying therapies dmts affect immune system may impact immune responses covid19 vaccines people ms objective article provide information immune system responses vaccinations review previous studies vaccine responses people ms support safety importance receiving currently available emerging covid19 vaccines immunological studies shown coordinated interactions t b lymphocytes adaptive immune system key successful generation immunological memory production neutralizing antibodies following recognition vaccine antigens innate immune cells cd4+ t cells essential facilitate cd8+ t cell b cell activation b cells drive sustain t cell memory data suggest classes dmt including type 1 interferons glatiramer acetate may significantly impair response vaccination dmtssuch sphingosine1phosphate receptor modulators sequester lymphocytes circulation alemtuzumab anticd20 therapies rely depleting populations immune cellshave shown attenuate responses conventional vaccines currently three covid19 vaccines granted emergency use authorization usa basis promising interim findings ongoing trials analyses vaccines people ms available decisions regarding covid19 vaccination dmt choice informed data expert consensus personalized considerations disease burden risk infection factorspmid34075554 doi101007 s12325021017613,0.0
positivity oligoclonal bands cerebrospinal fluid predisposed metabolic changes rearrangement inhibitory excitatory neurotransmitters subcortical brain structures multiple sclerosis mult scler relat disord 2021 apr 27 52102978 doi 101016 jmsard2021102978 online ahead printabstractbackground latest diagnostic criteria multiple sclerosis ms revitalized role oligoclonal bands synthesis cerebrospinal fluid csfocb study identifies predictors csfocbpositivity among vivo metabolic markers subcortical gray white matter ms patients first episode cis patients relapsingremitting course rrms methods study enrolled 13 cis 23 rrms patients metabolism evaluated using meschergarwoodedited protonmagnetic resonance spectroscopy 3t mr scanner addition nacetylaspartate tnaa myoinositol mins choline creatine compounds tcho tcr also evaluated aminobutyric acid gaba glutamateglutamine glx ratiosresults csfocbpositivity found 769 cis 782 rrms patients gaba glx ratios putamen corpus callosum strongly determined csfocbpositive cis patients essential predictors csfocbpositive cis mins glx ratios putamen tcho tnaa corpus callosum rrms gaba ratios right thalamus glx ratios left hippocampus strongly predicted csfocbpositive patients tcho tnaa tnaa tcr left hippocampus also identified essential predictors csfocbpositive rrms patientsconclusion first vivo evidence gabaglx rearrangement csfocbpositive patients since early stages mspmid34015640 doi101016 jmsard2021102978,0.0
validity reliability turkish canadian occupational performance measure copmtr people multiple sclerosis occup ther health care 2021 jun 14112 doi 101080 0738057720211933673 online ahead printabstractthe canadian occupational performance measure copm generic questionnaire based semistructured interview aimed translate turkish version copm copmtr assess reliability validity copmtr administered 82 participants 422 116 years 329 participants male multiple sclerosis ms convergent validity reliability analysis copmtr administered multiple sclerosis quality life54 msqol54 expanded disability status scale edss determine convergent validity testretest reliability week interval assessed intraclass correlation coefficient icc moderately strong negative correlations edss performance satisfaction score copmtr moderately strong positive correlations msqol54 physical performance copmtr moderate positive correlations msqol54 physical satisfaction copmtr moderate positive correlations found msqol54 mental copmtr performance satisfaction scores test retest reliability copmtr performance indicated excellent reliability current study demonstrates copmtr valid reliable tool measuring perceived occupational performance satisfaction people mspmid34126836 doi101080 0738057720211933673,0.0
potential medicinal value celastrol synthesized analogues central nervous system diseases biomed pharmacother 2021 apr 14 139111551 doi 101016 jbiopha2021111551 online ahead printabstractthe central nervous system cns vital part human nervous system incidence cns disease increasing year year become major public health problem prominent social problem present drugs commonly used clinic receptor regulators neurotransmitter inhibitors accompanied serious side effects therefore identification new drugs treatment strategies cns disease research hotspot medical field celastrol highly bioactive pentacyclic triterpenoid isolated tripterygium wilfordii hook f proved wide range pharmacological effects antiinflammation immunosuppression antiobesity antitumor activity however due poor water solubility low bioavailability toxicity clinical development trials celastrol postponed however recent years extensive medical value celastrol treatment cns diseases nervous system tumors alzheimers disease parkinsons disease cerebral ischemia multiple sclerosis spinal cord injury amyotrophic lateral sclerosis gradually attracted intensive attention worldwide particular celastrol nonnegligible antitumor efficacy 100 effective antitumor drugs study structural modification obtain better leading compounds higher efficiency lower toxicity aroused strong interest pharmaceutical chemists review research progress celastrol cns diseases synthesis celastroltype triterpenoid analogues application evaluation disease models cns diseases autotoxicityrelated target organ cancers past decade summarized detail order provide reference future better application treatment cns diseasespmid33865016 doi101016 jbiopha2021111551,0.0
employing metabolomic approaches determine influence age experimental autoimmune encephalomyelitis eae mol immunol 2021 apr 16 1358494 doi 101016 jmolimm202104008 online ahead printabstractthe immune system plays critical role homeostasis body also pathogenesis autoimmunity dysregulation immune balance closely related age examine influence age autoimmunity pathophysiological features experimental autoimmune encephalomyelitis eae induced different ages elucidated basis plasmalevel metabolic changes present study female 6 weekold 6 w 15 monthold 15 m c57bl 6 mice immunized eae induction plasma tissue samples collected determine phenotypic characteristics activity nadph oxidase plasma il6 concentrations brain spinal cord higher eae groups compared control groups well 15 m eae 15 group compared 6 w eae 6 group metabolomic profiles related characteristics eae characterized biosynthesis unsaturated fatty acids metabolism tryptophan tyrosine sphingolipid reduced availability unsaturated fatty acids perturbations tryptophan metabolism high risk factors eae development regardless age changes tyrosine metabolism sphingolipid metabolites dramatic 15 group findings can concluded changes unsaturated fatty acid tryptophan metabolism contributed development eae whereas changes sphingolipid tyrosine metabolism corresponded age additional risk factors influenced incidence severity eaepmid33873097 doi101016 jmolimm202104008,0.0
measure fluctuating impairments people ms development ambulatory assessment version eq5d5l exploratory study qual life res 2021 mar 12 doi 101007 s11136021028028 online ahead printabstractbackground health fluctuations even within single day typical multiple sclerosis ms captured widely used questionnaires like eq5d5l exploratory study aimed develop ambulatory assessment aa version eq5d5l eq5daa patients rate health mobile phones multiple times per day several days assess feasibility face validitymethods initial eq5daa version based two patient focus groups tested continuously developed iterative process patients completed several days followed debriefing interviews findings used refine eq5daa resulting version tested subsequent wave patients participants declared need changes anymore aa period participants completed standard paperbased eq5d5l asking todayresults focus group participants reported impairments often fluctuated within days regarded aa three assessments per day seven days appropriate assessment retrospective previous assessment items assessed time point four waves aa testing conducted thirteen 17 participants preferred aa standard assessment regarded informative burdensomeconclusion newly developed oneweek aa eq5d5l captures withinday daytoday health fluctuations people ms patients perspective feasible face valid way provide important information beyond captured standard eq5d5lpmid33710593 doi101007 s11136021028028,0.0
diabetes individuals tuberous sclerosis complex treated mtor inhibitors pediatr neurol 2021 apr 2 120710 doi 101016 jpediatrneurol202103007 online ahead printabstractbackground tuberous sclerosis complex tsc genetic disorder manifested multiple body systems mammalian target rapamycin mtor inhibitor mtori either everolimus sirolimus now routinely prescribed multiple clinical manifestations tsc including subependymal giant cell astrocytoma epilepsy medications generally well tolerated side effects previously identified welldesigned clinical trials tend mild readily manageable regulatory approvals treatment tsc expanded use everolimus sirolimus clinically enlarging clinician experience enabling identification potential treatmentrelated effects rarer identified recognized previous clinical trialsmethods medical records clinical patients tsc center treated mtori later developed diabetes mellitus dm analyzed compared treated mtori eight individuals received detailed analysis including laboratory results concomitant medications body mass indicesresults among 1576 individuals tsc 4 taking mtori developed diabetes compared 06 mtori showing significant interaction dm mtori chisquare 181 p 0001 details eight patients developed dm presentedconclusions longterm use mtori agents tsc may contribute risk diabetes early detection can critical management additional studies need investigate causal relationship clinicians aware possible association initiating monitoring ongoing treatmentpmid33962348 doi101016 jpediatrneurol202103007,0.0
gender differences geriatric syndromes mental illness nervous system diseases hospitalized thai older patients psychogeriatrics 2021 apr 13 doi 101111 psyg12679 online ahead printabstractbackground older persons affected mental neurological disorders differently gender plays significant role influencing geriatric disorder differentiation accordingly study characterized gender differences geriatric syndromes among hospitalized elderly thai patientsmethods probabilities disease occurrence reflecting gender differences calculated using historical data obtained ministry public health website thailand selected older patients aged 60 years admitted inpatient departments public hospitals mental disorders nervous system diseases 2014 2018 counting 160 000 cases year descriptive statistics odds ratios ors used analyse demonstrate gender differencesresults compared older females older males higher occurrences four mental disorders revealed 95 confidence interval ci values substance abuse 574 508649 alcohol use 566 544589 behavioural problems 134 131137 schizophrenia 110 106114 lower incidences older males seen values three mental disorders neurotic issues 046 044049 mood disorders 058 056060 dementia 091 088094 neurological disorders men similar higher incidences epilepsy 167 163172 cerebral palsy 161 157165 nervous system inflammatory diseases 153 146160 ischaemic attacks 142 136148 miscellaneous nervous disorders 120 118122 parkinsons disease 115 112119 contrast older men lower incidences multiple sclerosis 055 035086 migraines 066 062070 alzheimers disease 075 071078 conclusion accurate characterization gender differences geriatric syndromes can better inform policies appropriate early detection prevention contribute development treatment intervention various issues affecting elderly men womens healthpmid33847418 doi101111 psyg12679,0.0
virtual visits chronic neurologic disorders covid19 pandemic neurol sci 2021 mar 27 doi 101007 s10072021052123 online ahead printabstractbackground covid19 pandemic boosted telemedicine medical clinical practice experiences management chronic neurological disorders limited scattered aim study evaluate feasibility efficacy virtual visit chronic neurological disorders covid19 pandemicmethods patients scheduled visit lockdown period contacted patients fell four categories 1 longterm followup patient rescheduled 2 visit necessary teleconsultation accepted 3 problem solved phone call 4 visit necessary teleconsultation feasible visit maintained google meet used virtual visit neurological examination performed demographic clinical characteristics recordedresults end may 2020 184 virtual visits 178 patients performed following diseases myasthenia gravis 47 patients multiple sclerosis 79 epilepsy 12 headache 6 parkinsonism 34 patients 70 males 108 females mean age 535 years range 1390 virtual visit able obtain satisfactory neurological examinationconclusions demonstrated feasibility effectiveness virtual visit management large group patients common chronic neurological disorderspmid33774762 doi101007 s10072021052123,0.0
bioisostere dimebon latrepirdine delays onset slows progression pathology fus transgenic mice cns neurosci ther 2021 mar 23 doi 101111 cns13637 online ahead printabstractaims assess effects df402 bioisostere dimebon latrepirdine disease progression transgenic model amyotrophic lateral sclerosis als caused expression pathogenic truncated form human fus proteinmethods mice received df402 age 42 days onset clinical signs disease duration animal lifespan monitored experimental control animals multiple parameters gait assessed throughout presymptomatic stage using catwalk system followed bioinformatic analysis rnaseq used compare spinal cord transcriptomes wildtype untreated df402treated fus transgenic miceresults df402 delays onset slows progression pathology developed catwalk analysis protocol allows detection gait changes fus transgenic mice effect df402 gait already early presymptomatic stage stage limited number genes significantly change expression transgenic mice 60 genes df402 treatment causes reversion expression patternconclusion df402 slows disease progression mouse model als consistent previously reported neuroprotective properties dimebon bioisosteres results suggest structures can considered lead compounds optimization obtain novel medicines might used components complex als therapypmid33754495 doi101111 cns13637,1.0
fundamental mechanistic insights rare paradigmatic neuroimmunological diseases nat rev neurol 2021 may 28 doi 101038 s41582021004967 online ahead printabstractthe pathophysiology complex neuroimmunological diseases multiple sclerosis autoimmune encephalitis remains puzzling various mechanisms difficult dissect seem contribute hampering understanding processes involved rare neuroimmunological diseases easier study presentation pathogenesis homogeneous investigation diseases can provide fundamental insights neuroimmunological pathomechanisms can turn applied complex diseases review summarize key mechanistic insights three rare paradigmatic neuroimmunological diseases susac syndrome rasmussen encephalitis narcolepsy type 1 consider implications insights study neuroimmunological diseases diseases combination findings humans different modalities investigation animal models enabled triangulation evidence validate consolidate pathomechanistic features develop diagnostic therapeutic strategies approach provided insights directly relevant neuroimmunological diseases applicable contexts also outline nextgeneration technologies refined animal models can improve understanding pathomechanisms including cellspecific antigenspecific cns immune responses thereby paving way development targeted therapeutic approachespmid34050331 doi101038 s41582021004967,0.0
finemapping transancestral genomic analyses identify causal variants cells genes drug targets type 1 diabetes nat genet 2021 jun 14 doi 101038 s41588021008805 online ahead printabstractwe report largest diverse genetic study type 1 diabetes t1d date 61 427 participants yielding 78 genomewidesignificant p 5 108 regions including 36 new define credible sets t1dassociated variants show enriched immunecell accessible chromatin particularly cd4+ effector t cells using chromatinaccessibility profiling cd4+ t cells 115 individuals map chromatinaccessibility quantitative trait loci identify five regions t1d risk variants colocalize chromatinaccessibility quantitative trait loci highlight rs72928038 bach2 candidate causal t1d variant leading decreased enhancer accessibility bach2 expression t cells finally prioritize potential drug targets integrating genetic evidence functional genomic maps immune proteinprotein interactions identifying 12 genes implicated t1d targeted clinical trials autoimmune diseases findings provide expanded genomic landscape t1dpmid34127860 doi101038 s41588021008805,0.0
baicalin protects lpsinduced bloodbrain barrier damage activates nrf2mediated antioxidant stress pathway int immunopharmacol 2021 jul 96107725 doi 101016 jintimp2021107725 epub 2021 may 28abstractthe integrity bbb closely related brain microvascular endothelial cells tjs dysfunction can lead stroke multiple sclerosis extracranial injury neurodegenerative diseases baicalin one main bioactive extracts scutellaria baicalensis georgi antiinflammatory antioxidation pharmacological functions preventive protection baicalin seven consecutive days can significantly improve appearance cell apoptosis fluorescein sodium infiltration brain tissue balb c mice addition baicalin can inhibit production proinflammatory cytokines induced lps mice bend3 cells including il1 tnf time lps caused decrease tight junction proteins bloodbrain barrier baicalin can alleviate damage bloodbrain barrier upregulating claudin5 zo1 protein expression addition results showed baicalin reduced production ros mda bend3 cells promoted production sod upregulated expression nrf2 ho1 nqo1 mechanism change mediated activating nrf2 signaling pathway baicalin protected lpsinduced bloodbrain barrier damage activateed nrf2mediated antioxidant stress pathwaypmid34162131 doi101016 jintimp2021107725,0.0
secondary cluster headache due contralateral demyelinating periaqueductal gray matter lesion headache 2021 jul 61 7 11361139 doi 101111 head14180abstractobjectives background tensiontype headache migraine without aura common primary headaches occurring people demyelinating diseases whereas cluster headache ch can considered exceptional location demyelinating lesions strategic cases involving areas interacting trigeminovascular systemmethods results report case 54yearold woman rightsided ch initial manifestation multiple sclerosis showing left dorsal brainstem lesion magnetic resonance imaging region dorsal longitudinal fasciculus dlf conclusion case seems suggest possible role dlf process leads ch attacks neuroimaging clearly showed lesion contralateral ch pain hypothesize fibers periaqueductal gray matter project contralateral side besides known ipsilateral connectionspmid34363407 doi101111 head14180,1.0
instrumentally assessed gait quality relevant gait endurance velocity explain patientreported walking ability early stage multiple sclerosis eur j neurol 2021 apr 17 doi 101111 ene14866 online ahead printabstractbackground people multiple sclerosis pwms often report walking limitations even goldstandard expanded disability status scale edss indicates normal walking endurance autonomy present multicenter study earlystage pwms aims analyzing aspects associated patientreported walking limitations measured 12item multiple sclerosis walking scale msws12 methods eightytwo pwms edss25 assessed using fullerton advanced balance scaleshort fabs fatigue severity scale fss 6minute walk test 6mwt latter administered also 21 healthy subjects hs participants performed 6mwt wearing three inertial sensors ankles trunk instrumented metrics describing gait velocity stride length frequency quality regularity symmetry instability computed sensors data fatigue fss balance fabs walking endurance 6mwt instrumented metrics entered multiple regression model msws12 dependent variableresults gait symmetry gait instability fatigue balance significantly associated selfrated walking ability walking endurance velocity fatigue balance gait symmetry instability impaired participants reporting mildtomoderate msmmpwl 25msws1275 compared reporting nonetominimal msnmpwl 0msws1225 perceived walking limitations compared hs gait symmetry stability reduced msnmpwl msmmpwl even participants edss15conclusion instrumentallyassessed gait quality aspects symmetry instability associated patientreported walking ability earlystage pwms seem sensitive biomarkers detect subtle impairments even earliest stages disease edss15 future studies assess ability follow walking change due ms progression pharmacological rehabilitation interventionspmid33864413 doi101111 ene14866,0.0
mindfulness group intervention newly diagnosed persons multiple sclerosis pilot study mult scler relat disord 2021 may 8 52103016 doi 101016 jmsard2021103016 online ahead printabstractbackground relapsing ms rms lifelong disease without cure usually diagnosed 2040 years age newly diagnosed rms highly stressful event due unpredictable disease course diagnosis thus imperative persons ms skills support cope negative physical emotional effects disease objective study assess whether mindfulnessbased intervention mbi improve coping skills thus lessen negative consequences stress due newly diagnosed rmsmethods singleblind assessor randomized prospective study 10week mbi vs usual standard care persons newly diagnosed within 1 year rms recruited one tertiary care ms clinic london canada mbi administered group format trained mbi facilitator primary outcomes included brief cope measure hospital anxiety depression scale hads subscales secondary outcomes included measures perceived stress cognitive function fatigue quality life exploratory tertiary outcomes included serum markers inflammation stress subjects assessed baseline post intervention equivalent 6 months later repeated measures multivariate analysis covariance mancova used baseline scores employed covariates test scores compare longitudinal changes immediately mbi sessions 6 months laterresults twentyfive subjects recruited 16 mbi 9 controls two fall spring mbi interventions 15 years controls completed study 4 mbi participants leaving 21 subjects analysis women 17 81 mean age 371 94 years two thirds already started dmt time consent median edss 20 0040 groups well matched baseline characteristics exception months since diagnosis mbi 64 65 vs control 36 28 p0023 controls completed study 4 mbi participants mbi group improved significantly cope measure compared control group p0024 pre post intervention mbi group also improved significantly hads depression subscale p0007 significant difference time hads anxiety subscale p0179 effect size cope 056 040 hadsd secondary outcomes significant improvement perceived stress scale p0015 exploratory outcomes significantly different none outcomes significant sixmonth followupconclusion pilot study demonstrates mbi may improve coping depression perceived stress newly diagnosed within one year persons rms short term future research confirm results well investigate measures extend benefit beyond immediate interventionpmid34020388 doi101016 jmsard2021103016,0.0
costofillness progression diagnosis multiple sclerosis nationwide registerbased cohort study sweden people newly diagnosed multiple sclerosis populationbased matched reference group pharmacoeconomics 2021 may 10 doi 101007 s40273021010354 online ahead printabstractbackground multiple sclerosis ms chronic disease associated increased healthcare utilisation productivity lossesobjective objective study explore progression healthcare costs productivity losses diagnosis ms comparison populationbased matched reference groupmethods conducted nationwide swedish registerbased cohort study workingaged people ms diagnosed 201012 n 1988 populationbased matched references without ms n 7981 nine years observation spanned 4 years prior y4 4 years y+4 year diagnosis y0 differences annual allcause healthcare costs inpatient specialised outpatient healthcare well pharmacydispensed prescribed drugs costs productivity loss days sickness absence disability pension estimated people ms references using t tests 95 confidence intervals average excess costs ms estimated using generalised estimating equation modelsresults people multiple sclerosis higher costs diagnosis ms also thereafter mean differences healthcare costs productivity losses people ms matched references y4 216 eur 95 confidence interval 58374 1540 eur 95 confidence interval 8482233 larger cost excesses observed later study years summarising 9 study years people ms fivefold higher excess healthcare costs references twice high productivity lossesconclusions excess healthcare costs productivity losses occur already diagnosis ms increase time excess costs findings diagnosis suggest earlier diagnosis might lead reduced excess costs ms timepmid33970446 doi101007 s40273021010354,0.0
clinical radiological activity secondary progressive multiple sclerosis populationbased cohort eur j neurol 2021 apr 10 doi 101111 ene14861 online ahead printabstractbackground patients secondary progressive multiple sclerosis sp ms clinical radiological activity likely benefit disease modifying treatments evaluate proportions year progression onset studied patients sp ms onset 2002 2012 populationbased multiple sclerosis registry northeastern francemethods progression onset first identified neurologists diagnosis n cohort using automated datadriven definition d cohort given year onset progression clinical activity defined least one relapse radiological activity least one new t2 gadoliniumenhancing lesion multivariate mixed logistic regression used assess factors associated activity yearresults n cohort among 833 patients sp ms median followup 8 years 100 148 least one relapse year first 5 years progression including clinical radiological activity increased proportions 119 237 proportion mri scan year ranging 298 405 first year progression young age high relapse rate 5 years progression associated activity given year d cohort results confirmed findingsconclusions substantial proportion patients sp ms present disease activity studies evaluate impact disease modifying treatments disease course patientspmid33838072 doi101111 ene14861,0.0
biologic treatment algorithms moderatetosevere psoriasis comorbid conditions special populations review j clin dermatol 2021 apr 16 doi 101007 s4025702100603w online ahead printabstractthe emergence data clinical trials biologics approval new biologics improved understanding psoriasis pathogenesis increased therapeutic possibilities treatment moderatetosevere psoriasis biologics currently approved treatment psoriasis include tumor necrosis factor inhibitors interleukin il 17 inhibitors ustekinumab il12 23 inhibitor il23 inhibitors data clinical trials studies safety efficacy biologics provide essential information personalization patient care discuss benefits disadvantages biologics firstline treatment choice update treatment recommendations according current evidence propose psoriasis treatment algorithms discussion includes following comorbid conditions psoriatic arthritis multiple sclerosis congestive heart failure inflammatory bowel disease hepatitis b nonmelanoma skin cancer lymphoma latent tuberculosis make evidencebased treatment recommendations special populations including pediatric patients patients coronavirus 2019 covid19 pregnant breastfeeding patients psoriasis ultimately individualized recommendations consider patient preferences disease severity comorbid conditions additional risk factors offered patients updated new trial data emergespmid33861409 doi101007 s4025702100603w,0.0
autoimmune encephalitis proposed best practice recommendations diagnosis acute management j neurol neurosurg psychiatry 2021 mar 1jnnp2020325300 doi 101136 jnnp2020325300 online ahead printabstractthe objective paper evaluate available evidence step autoimmune encephalitis management provide expert opinion evidence lacking paper approaches autoimmune encephalitis broad category rather focusing individual antibody syndromes core authors autoimmune encephalitis alliance clinicians network reviewed literature developed first draft evidence lacking controversial electronic survey distributed members solicit individual responses sixtyeight members 17 countries answered survey corticosteroids alone combined agents intravenous ig plasmapheresis selected firstline therapy 84 responders patients general presentation 74 patients presenting faciobrachial dystonic seizures 63 nmdarigg encephalitis 485 classical paraneoplastic encephalitis half responders indicated add secondline agent response one firstline agent 32 indicated adding secondline agent response one firstline agent 15 indicated using secondline agent patients preferred secondline agent 80 responders chose rituximab 10 chose cyclophosphamide clinical scenario unknown antibodies detailed survey results presented manuscript summary diagnostic therapeutic recommendations presented conclusionpmid33649022 doi101136 jnnp2020325300,0.0
2 2benzofuranyl 2imidazoline attenuates disruption bloodbrain barrier eae via nmdar neurochem res 2021 mar 27 doi 101007 s11064021033042 online ahead printabstractbloodbrain barrier bbb disruption recognized early hallmark multiple sclerosis ms pathology previous studies shown 2 2benzofuranyl 2imidazoline 2bfi protected experimental autoimmune encephalomyelitis eae classic animal model ms however potential effects 2bfi bbb permeability yet evaluated context eae herein aimed investigate effect 2bfi bbb permeability animal model vitro bbb model using tnf imitate inflammatory damage bbb ms animal model 2bfi reduced neurological deficits bbb permeability eae mice compared saline treatment western blot results indicated 2bfi alleviated loss tight junction protein occludin caused eae also inhibited activation nr1erk signaling pathway vitro bbb model 2bfi 100 m alleviated tnfinduced increase permeability reduction expression occludin monolayer bend3 cells similar protective effects also observed treatment nmdar antagonist mk801 western blot results showed tnfinduced bbb breakdown increase nmdar subunit 1 nr1 levels erk phosphorylation blocked pretreatment 2bfi mk801 however additional effect observed bbb permeability expression occludin perk pretreatment 2bfi mk801 study indicates 2bfi alleviates disruption bbb context inflammatory injury similar ms targeting nmdar1 well likely activating subsequent erk signaling pathway results provide evidence 2bfi potential drug treatment mspmid33772673 doi101007 s11064021033042,0.0
medications multiple sclerosis risk malignancy next neurotherapeutics 2021 aug 18 doi 101007 s13311021011075 online ahead printabstractmany autoimmune diseases confer higher risk cancer patients compared general population controversial factor tying autoimmune diseases malignancy harm immunosuppressive treatment nonetheless multiple sclerosis different autoimmune diseases findings disease populations may apply issue neurotherapeutics dolladile colleagues france present new evidence risks cancers patients multiple sclerosis treated diseasemodifying therapies based analyses spontaneous reporting data commentary discusses context limitations implications findingspmid34409568 doi101007 s13311021011075,0.0
safety tolerability nabiximols oromucosal spray review 15 years#39 accumulated evidence clinical trials expert rev neurother 2021 jun 7 doi 101080 1473717520211935879 online ahead printabstractintroduction nabiximols cannabinoidbased oromucosal spray indicated addon therapy symptomatic relief spasticity persons multiple sclerosis ms review compiles tolerability safety data clinical trials investigated nabiximols spasticity chronic painareas covered systematic searches identified 38 placebocontrolled randomised controlled trials rcts postrct openlabel studies reporting safety data 15 mainly ms spasticity 16 neuropathic pain six chronic cancer pain one rheumatoid arthritis pain rcts discontinuation rates due adverse events aes nabiximols placebo lower spasticity studies 54 28 respectively neuropathic pain 129 53 cancer pain 195 166 studies consistently identified aes dizziness nausea fatigue spasticity neuropathic pain studies dizziness nausea vomiting somnolence cancer pain studies serious ae sae rates nabiximols placebo higher cancer pain studies 218 169 ms spasticity 47 vs 08 neuropathic pain 41 vs 31 studies despite similar dose ranges treatmentrelated saes showed particular patternexpert opinion 15 years investigation nabiximols oromucosal spray spasticity chronic pain conditions indicates acceptable overall safety profilepmid34092180 doi101080 1473717520211935879,0.0
mri detect localize area postrema multiple sclerosis role 3ddir 3dflair j neuroimaging 2021 apr 30 doi 101111 jon12867 online ahead printabstractbackground purpose area postrema ap highly vascularized paired 2 mmlong anatomical structure localized dorsal inferior surface medulla oblongata caudal end fourthventricle ap principally affected ap syndrome commonly associated autoimmune inflammatory diseases including essentially neuromyelitis optica spectrum disorder nmosd aim study assess best cerebral mri sequences planes ap detection order assist aid diagnosis difficult nmosd casesmethods 3dt1 2dt2 3dfluidattenuated inversion recovery 3dflair 3ddouble inversion recuperation 3ddir routinely used inflammatory diseases analyzed scored based quality 02 ability detect ap plane 0 detection 1 probable detection 2 obvious detection based image availability subjects divided three groups group1 including 100 randomly selected subjects 3dt1 3dflair group2 including 30 multiple sclerosis ms patients observatoire franais de la sclrose en plaques ofsep 3dt1 3dflair 3ddir group3 including 164 ofsep ms patients 3dflair 2dt2results ap undetectable 3dt1 2dt2 ap detected 87 3dflair group1 90 group2 90 group3 ap also detected 100 3ddir images axial planeconclusions evidenced ap easily assessed 3ddir 3dflair emphasizing importance adding sequences nmosd mriprotocols moreover effective imaging plane identifying ap axial planepmid33930239 doi101111 jon12867,0.0
transcutaneous spinal cord stimulation improves postural stability individuals multiple sclerosis mult scler relat disord 2021 may 7 52103009 doi 101016 jmsard2021103009 online ahead printabstractbackground widespread demyelination central nervous system can lead progressive sensorimotor impairments following multiple sclerosis compromised postural stability standing common consequence clinical strategies needed improve postural stability following multiple sclerosis objective study therefore investigate effect noninvasive transcutaneous spinal stimulation postural stability upright standing individuals multiple sclerosismethods center pressure displacement electromyograms soleus tibialis anterior recorded seven individuals multiple sclerosis standing without transcutaneous spinal stimulation center pressure muscle activity measures calculated compared stimulation transcutaneous spinal stimulation conditions relationship center pressure displacement electromyograms quantified using crosscorrelation analysisresults transcutaneous spinal stimulation postural stability significantly improved standing eyes closed time frequencydomain measures obtained anteriorposterior center pressure fluctuation decreased increased respectively tibialis anterior activity lower compared stimulation conversely differences found stimulation transcutaneous spinal stimulation standing eyes openconclusion following multiple sclerosis transcutaneous spinal stimulation improved postural stability standing eyes closed presumably catalyzing proprioceptive function future work confirm underlying mechanisms explore clinical value transcutaneous spinal stimulation individuals multiple sclerosispmid34023772 doi101016 jmsard2021103009,1.0
comparison isometric concentric motor fatigability persons multiple sclerosis healthy controls exploring central peripheral contributions motor fatigability neurorehabil neural repair 2021 may 2215459683211017502 doi 101177 15459683211017502 online ahead printabstractbackground motor fatigability ie contractioninduced reduction muscle strength concentric task associate stronger walking perception fatigue persons multiple sclerosis pwms compared isometric task however central peripheral contributions motor fatigability tasks investigatedobjective compare central peripheral contributions motor fatigability knee extensors sustained isometric fatigability protocol versus concentric fatigability protocol pwms versus healthy controls hcs methods participants n31 pwms n15 hcs underwent neuromuscular testing immediately two knee extensor fatigability tasks sustained isometric concentric isokinetic dynamometer neuromuscular testing fatigability consisted maximal voluntary contraction voluntary activation central neural contributor resting twitch peripheral muscular contributor determined interpolated twitch techniqueresults sustained isometric concentric fatigability protocols resulted motor fatigability pwms hcs betweenprotocols differences either group regression analysis showed motor fatigability variance pwms mainly attributed central fatigability sustained isometric protocol central peripheral fatigability concentric protocol hcs variance sustained isometric concentric fatigability attributed peripheral central fatigabilityconclusion central peripheral contributions motor fatigability differed sustained isometric concentric protocols well pwms hcs betweenprotocol differences pwms provide neuromuscular dimension reported difference strength associations concentric isometric tasks walking perception fatigue pwmspmid34027727 doi101177 15459683211017502,0.0
comparative efficacy safety ozanimod dimethyl fumarate relapsingremitting multiple sclerosis using matchingadjusted indirect comparison cns drugs 2021 apr 13 doi 101007 s40263021008050 online ahead printabstractbackground patients multiple sclerosis ms experience relapses sustained disability progression since 2004 number diseasemodifying therapies dmts ms grown substantially result patients healthcare providers insurers increasingly interested comparative efficacy safety evaluations distinguish treatment options headtohead studies dmts limitedobjective aim current study compare efficacy safety outcomes dmts ozanimod dimethyl fumarate dmf using matchingadjusted indirect comparison maic adjust crosstrial differences study design populationmethods systematic literature review performed identify clinical studies evaluating efficacy safety ozanimod compared dmf individual patientlevel data ipd ozanimod obtained sunbeam radiance part b trials aggregatelevel patient data apd dmf obtained confirm define maic used weight ipd apd based important baseline patient characteristics considered effect modifiers prognostic factors order balance covariate distribution establish homogenous trial populations trial populations determined sufficiently homogenous outcomes interest estimated used generate treatment effects weighted ipd apd used maic methodology compare efficacy safety outcomes interest ozanimod 10 mg daily od dmf 240 mg twice daily bid including confirmed disability progression cdp 3 6 months annualized relapse rate arr proportion patients relapsed overall adverse events aes serious aes saes discontinuations due aesresults matching patient data baseline patient characteristics balanced patients receiving ozanimod receiving dmf compared dmf ozanimod demonstrated significantly improved cdp 3 months hazard ratio 067 95 confidence interval ci 053086 arr rate ratio rr 080 95 ci 067097 proportion patients relapsed odds ratio 066 95 ci 052083 overall aes 011 95 ci 008016 saes 027 95 ci 019039 discontinuations 011 95 ci 007017 cdp 6 months differ significantly two agents rr 089 95 ci 062126 conclusions adjustment baseline patient characteristics maic demonstrated efficacy safety ozanimod 10 mg od superior dmf 240 mg bid although maic less likely produce biased estimates nave standard indirect treatment comparison via common comparator limitations include potential confounding due unobserved thus unaccounted baseline differencespmid33847901 doi101007 s40263021008050,0.0
physical activity may contribute brain health multiple sclerosis mr volumetric spectroscopy study j neuroimaging 2021 may 6 doi 101111 jon12869 online ahead printabstractbackground purpose physical activity may represent diseasemodifying therapy persons multiple sclerosis pwms date limited research regarding mechanisms based brain imaging understanding beneficial effects physical activity pwms study examined relationship physical activity levels thalamic hippocampal volumes brain metabolism pwmsmethods sample 52 pwms 373 96 years age 35 females 17 males underwent combination volumetric magnetic resonance imaging magnetic resonance spectroscopy current lifetime physical activity assessed using actigraphy adapted version historical activity questionnaire respectivelyresults positive associations observed actigraphy selfreported levels moderatetovigorous physical activity mvpa thalamic hippocampal volumes regarding brain metabolism actigraphy selfreported levels mvpa positively associated higher hippocampal thalamic levels nacetylaspartate creatine ratio naa cr marker neural integrity cell energy state conclusions study provides novel evidence positive association physical activity thalamic hippocampal volume metabolism pwms findings support hypothesis physical activity particularly mvpa may serve diseasemodifying treatment improving brain health pwmspmid33955618 doi101111 jon12869,0.0
cytotoxic profile cd3+cd20+ t cells progressive multiple sclerosis mult scler relat disord 2021 may 7 52103013 doi 101016 jmsard2021103013 online ahead printabstractrecently shown highly effective anticd20 therapies used ms patients deplete cd20+ b cells also small subset t cells expressing cd20 surface marker cd3+cd20+ t cells demonstrated progressive ms patients cd3+cd20+ t cells share ability express cytotoxic factors perforin serineprotease granzymeb gzmb classically associated cd8+ t cells functionality beyond cluster analyses show set activation markers transcriptional factors related cd8 effector program also expressed cd3+cd20+ t cells characterization surface functional markers cd3+cd20+ t subsets may helpful development new therapeutic strategies mainly progressive ms patients well assessing pathophysiological effects highly effective anticd20 therapiespmid34030100 doi101016 jmsard2021103013,0.0
plasma interleukin33 level relapsingremitting multiple sclerosis negatively correlated central nervous system lesions patients mild disability clin neurol neurosurg 2021 may 20 206106700 doi 101016 jclineuro2021106700 online ahead printabstractbackground cytokines chemokines undoubtedly involved pathogenesis multiple sclerosis ms many reports suggest significant role interleukin33 il33 course ms development clear whether negative positive therefore investigated plasma il33 levels patients relapsingremitting ms rrms methods study consisted rrms patients n 73 healthy subjects n 54 blood samples taken plasma il33 levels determined using enzymelinked immunosorbent assay method patients also underwent laboratory imaging tests disability status assessedresults plasma il33 levels marginally significantly higher patients rrms p 007 higher il33 levels significantly associated higher age p 001 also statistically significant negative correlation plasma il33 levels number high signal intensity lesions t2weighted mri p 003 dividing number lesions groups 9 9 t2weighted lesions students ttest unrelated variables showed negative correlation statistically significant p 022 spearmans correlation showed marginally significant correlation p 006 il33 level number t2weighted lesions il33 also shown significant ability differentiate rrms patients healthy subjects sensitivity 99 specificity 70 p 000 conclusions patients rrms elevated plasma il33 levels rrms patients mild disability high plasma levels il33 may neuroprotective effects potentially stimulating remyelination suppressing autoimmune inflammation damage studies matter larger number patients neededpmid34030079 doi101016 jclineuro2021106700,1.0
towards objective classification multiple sclerosis mult scler 2021 jul 27 8 11511152 doi 101177 1352458520975325 epub 2020 dec 2no abstractpmid34156317 doi101177 1352458520975325,0.0
sensorimotor function predict quality life persons multiple sclerosis mult scler relat disord 2021 apr 28 52102986 doi 101016 jmsard2021102986 online ahead printabstractquality life qol reported reduced persons multiple sclerosis associations qol clinical severity disease well sensorimotor function shown reinvestigated impacting factors qol additional assessment depression fatigue satisfaction life battery endeffector based assessments sensorimotor functioning models multiple linear regression revealed everyday life activity limitations driving factor within used questionnaire association sensorimotor tests depression fatigue satisfaction life conclude either psychoemotional coping adaptability dominant determinant qol qol need quantitative objective reconceptualizationpmid33979773 doi101016 jmsard2021102986,0.0
unified framework identifies new links plasma lipids diseases electronic medical records across largescale cohorts nat genet 2021 jun 17 doi 101038 s4158802100879y online ahead printabstractplasma lipids known heritable risk factors cardiovascular disease increasing evidence also supports shared genetics diseases organ systems devised comprehensive threephase framework identify new lipidassociated genes study relationships among lipids genotypes gene expression hundreds complex human diseases electronic medical records genomics 347 traits uk biobank 549 traits aside 67 new lipidassociated genes strong replication found evidence pleiotropic snps genes lipids diseases across phenome include discordant pleiotropy hla region lipids multiple sclerosis putative causal paths triglycerides gout among several others findings give insights genetic basis relationship plasma lipids diseases phenomewide scale can provide context future prevention treatment strategiespmid34140684 doi101038 s4158802100879y,0.0
clinical experience plasmapheresis neuromyelitis optica patients mexico mult scler relat disord 2021 may 15 52103022 doi 101016 jmsard2021103022 online ahead printabstractbackground neuromyelitis optica spectrum disorders nmosds group chronic immunemediated demyelinating diseases central nervous system pathophysiology dependent humoral mediated responses caused autoreactive igg antibodies aquaporin4 water channels aqp4igg myelin oligodendrocyte glycoprotein mogigg plasma exchange plex proved beneficial therapy patients severe relapses present largest series latin american patients treated plex acute nmosds relapsesmethods retrospective study conducted selection included patients diagnosed nmosds received plex 20102019 irrespective aqp4igg serostatus patients received 5 grams iv methylprednisolone plex therapy initiated simultaneously iv steroids baseline postplex therapy expanded disability status scale edss measured identify acute response therapy comparison responders nonresponders also conducted subgroup analysis stratified response serostatus type clinical relapse time plexresults total 89 patients included mean age onset 38 1297 years 49 551 patients aqp4igg seropositive patients unilateral optic neuritis 348 longitudinally extensive transverse myelitis 337 mean time onset plex initiation 209 181 days response rate 393 mean decline edss 07 09 p 0001 decline edss response rate independent serostatus type clinical relapse time plex initiationconclusion plex appears effective therapy nmosds relapses even limited resources setting treatment initiation may delayed benefit seems independent type clinical relapse aqp4 igg serostatuspmid34034213 doi101016 jmsard2021103022,1.0
interleukin 2 ameliorates autoimmune neuroinflammation modulating balance t helper 17 cells regulatory t cells mouse ann clin lab sci 2021 jul 51 4 529534abstractobjective multiple sclerosis ms progressive autoimmunemediated inflammation central nervous system cns experimental autoimmune encephalomyelitis eae suitable model study pathogenesis ms il2 considered t cell growth factor antiinflammatory cytokine present study investigated effects low dose il2 treatment mouse eae therapymethod expression il2 il2 receptor predicted using public microarray data verified realtime pcr elisa mouse eae model mice injected myelin oligodendrocyte glycoprotein 3555 mog3555 subcutaneously induce eae model il2 treatment initiated 5 consecutive days day 15 post mog3555 immunization flow cytometry applied investigate proportions th17 treg cells elisa used detect concentrations il17a ifnr il10 tgfbresults study showed il2 treatment ameliorates clinical severity eae flow cytometry results indicated therapeutic effect related reduction th17 cells expansion treg cells eae spinal cord vitro experiments also confirmed antiinflammatory effect il2 eaereactivated t cellsconclusion lowdose il2 potential therapeutic strategy eae mspmid34452891,1.0
fibrous papules lips pediatr dermatol 2021 jun 28 doi 101111 pde14610 online ahead printabstractmultiple angiofibromas commonly found patients tuberous sclerosis complex report rare presentation multiple congenital fibrous papules occurring lips syndromic associationspmid34184319 doi101111 pde14610,0.0
correction novel small molecule trva242 stabilizes neuromuscular junction defects multiple animal models amyotrophic lateral sclerosis neurotherapeutics 2021 jun 7 doi 101007 s13311021010612 online ahead printno abstractpmid34100189 doi101007 s13311021010612,0.0
mixedmethods study cognitive performance persons multiple sclerosis association neuropsychological test performance interviews daily cognitive functioning mult scler relat disord 2021 mar 19 52102911 doi 101016 jmsard2021102911 online ahead printabstractbackground cognitive difficulties commonly reported persons multiple sclerosis ms however selfreports cognition often correspond well objective neuropsychological test performance use qualitative interviews can allow persons ms describe detail cognitive function impacted daily life also taking consideration personal environmental influences study knowledge examined association objective neuropsychological test performance qualitative interview reports daily cognitive function information help explain reported lack correspondence two methods evaluating cognitive function msobjective investigate relationship objective neuropsychological test performance qualitative interview reported daily cognitive function persons ms methods convergent parallel mixedmethods design whereby 12 persons ms mean age 47 9 female 7 relapsingremitting ms took part 2hour neuropsychological assessment including brief international cognitive assessment ms bicams followed semistructured qualitative interview probing daily cognitive functioning interview data analysed using thematic analysis interview codes themes compared neuropsychological performance respective cognitive domains without cognitive impairment bicamsresults based qualitative interview data commonly reported difficulties related memory word finding processing speed 43 0 33 individuals reporting deficits actually demonstrated impairment respective corresponding neuropsychological measures eleven twelve participants reported use strategies manage cognitive difficulties frequently reported strategies used related fatigue management personal age fatigue environmental factors pressure daily responsibilities availability support reported influencers daily cognitive function three 12 participants classified cognitively impaired bicams differ nonimpaired respect use strategies influence personal environmental factors daily cognitive functioningconclusions interviewreported daily cognitive difficulties correspond well objective neuropsychological performance greater emphasis placed utilizing developing objective neuropsychological measures greater sensitivity particularly word finding difficulties ms incorporation personal environmental factors interpretation neuropsychological test results almost participants reported use cognitive strategies feel greater emphasis needs placed patient education evidencebased strategies particularly focused highly reported impacted word finding processing speed abilitiespmid34111681 doi101016 jmsard2021102911,0.0
unraveling deep gray matter atrophy iron myelin changes multiple sclerosis ajnr j neuroradiol 2021 apr 22 doi 103174 ajnra7093 online ahead printabstractbackground purpose modifications magnetic susceptibility consistently demonstrated subcortical gray matter ms patients uncertainties remain concerning underlying neurobiological processes clinical relevance applied quantitative susceptibility mapping longitudinal relaxation rate relaxometry clarify relative contribution atrophy iron myelin changes deep gray matter damage disability msmaterials methods quantitative susceptibility mapping longitudinal relaxation rate maps computed 91 patients 55 healthy controls mr images acquired 3t applying external model estimated iron myelin concentration maps subjects subsequently changes deep gray matter iron myelin concentration atrophydependent content atrophyindependent investigated globally bulk analysis regionally voxelbased atlasbased thalamic subnuclei analyses clinical impact observed mri modifications evaluated via regression modelsresults identified reduced thalamic p 001 increased pallidal p 001 mean iron concentrations patients ms versus controls global myelin iron content basal ganglia differ two groups actual iron depletion present thalamus p 001 regionally patients showed increased iron concentration basal ganglia p 001 reduced iron myelin content thalamic posteriormedial regions p 004 particularly pulvinar p 001 disability predicted thalamic volume b 0341 p 02 iron concentration b 0379 p 005 content b 0406 p 009 well pulvinar iron b 0415 p 003 myelin b 0415 p 02 content independent atrophyconclusions quantitative mri suggests atrophyrelated iron increase within basal ganglia patients ms along atrophyindependent reduction thalamic iron myelin correlating disability absolute depletions thalamic iron myelin may represent sensitive markers subcortical gm damage add clinical impact thalamic atrophy mspmid33888456 doi103174 ajnra7093,1.0
imaging tumor predisposition syndromes radiologe 2021 jun 25 doi 101007 s0011702100861z online ahead printabstractclinical issue tumor predisposition syndromes tps heterogeneous group genetic cancers 10 approximately 2200 malignancies childhood germany develop due inherited disposition whereby tps may underdiagnosed focus review set imaging lifraumeni syndrome neurofibromatoses tuberous sclerosis overgrowth neuroendocrine syndromesstandard radiological methods order detect tumors early stage screening specific time intervals tps required ultrasonography magnetic resonance imaging mri especially wholebody mri particularly important imaging modalitiesmethodological innovations innovative mri techniques can increase image quality patient comfort mri acquisition time can significantly reduced optimized acceleration factors motion robust radial sequences joint acquisition readout multiple slices excitation thus shorter mri examinations can performed younger children without anesthesiapractical recommendation regular screening ultrasound mri can reduce morbidity mortality patients affected tpspmid34170362 doi101007 s0011702100861z,0.0
comorbidity patterns people multiple sclerosis latent class eur j neurol 2021 apr 30 doi 101111 ene14887 online ahead printabstractobjective identify clinically meaningful comorbidity patterns associations demographics clinical characteristics people multiple sclerosis ms study design setting conducted latent class analysis identify clinically distinct comorbidity patterns ms using 15 common comorbidities among 1 518 australian ms longitudinal study participants associations demographics clinical characteristics comorbidity patterns examined using logbinomial multinomial logistic regressionresults five distinct comorbidity patterns identified minimallydiseased class 308 participants one comorbidity metabolic class 227 mental healthallergy class 217 nonmetabolic class 76 severelydiseased class 70 participants higher prevalence comorbidities relative probabilities relative risk ratios 95 confidence intervals assigned comorbidity classes compared minimallydiseased class significantly increased participants older metabolic 109 106111 nonmetabolic 107 104111 severelydiseased 104 101108 female nonmetabolic 535 1981442 severelydiseased 221 102477 obese metabolic 406 245672 mental healthallergy 157 100246 severelydiseased 453 221929 moderate disability mental healthallergy 232 147364 severelydiseased 265 116604 conclusion comorbidity patterns exist ms women people older obese higher disability levels likely classes higher levels comorbidity findings may offer opportunities designing personalised approaches comorbidity prevention treatmentpmid33931923 doi101111 ene14887,0.0
nacylethanolaminehydrolyzing acid amidase inhibition fatty acid amide hydrolase inhibition prevents development experimental autoimmune encephalomyelitis mice neurotherapeutics 2021 jul 7 doi 101007 s1331102101074x online ahead printabstractnacylethanolamines naes endogenous bioactive lipids reported exert antiinflammatory neuroprotective effects mediated cannabinoid receptors peroxisome proliferatoractivated receptors ppars among others therefore interfering nae signaling promising strategy decrease inflammation neurological disorders multiple sclerosis ms fatty acid amide hydrolase faah nacylethanolaminehydrolyzing acid amidase naaa key modulators nae levels study aims investigate compare effect naaa inhibition faah inhibition dual inhibition enzymes mouse model ms namely experimental autoimmune encephalomyelitis eae data show naaa inhibition strongly decreased hallmarks pathology interestingly faah inhibition less efficient decreasing inflammatory hallmarks despite increased nae levels moreover inhibition naaa faah using dualinhibitor coadministration naaa faah inhibitors show added value compared naaa inhibition furthermore data suggest important role decreased activation astrocytes microglia effects naaa inhibition eae naaa inhibition affect t cell recall work highlights beneficial effects naaa inhibition context central nervous system inflammation suggests simultaneous inhibition naaa faah additional beneficial effect eaepmid34235639 doi101007 s1331102101074x,1.0
emerging concepts bradykinesia nonparkinsonian conditions eur j neurol 2021 apr 1 doi 101111 ene14851 online ahead printabstractbradykinesia one cardinal motor symptoms parkinsons disease however clinical experimental studies indicate bradykinesia may also observed various neurological diseases primarily characterized parkinsonism conditions include hyperkinetic movement disorders dystonia chorea essential tremor bradykinesia may also observed patients neurological conditions seen movement disorders including characterized involvement cerebellum corticospinal system dementia multiple sclerosis psychiatric disorders provide updated overview bradykinesia nonparkinsonian conditions discuss major findings clinical reports experimental studies pathophysiological standpoint bradykinesia neurological conditions primarily characterized parkinsonism may explained brain network dysfunction addition pathophysiological implications present paper highlights important terminological issues need new accurate widelyused definition bradykinesia context movement disorders neurological conditionspmid33793037 doi101111 ene14851,0.0
peripheral blood b cell subset ratios expression levels b cellassociated genes altered benign multiple sclerosis mult scler relat disord 2021 may 11 52103019 doi 101016 jmsard2021103019 online ahead printabstractthe interplay immune system sleep dysfunction cognitive impairment participates progression disability multiple sclerosis ms aim identify molecular pathways b cell associated separate components ms disability benign ms nonbenign ms patients healthy controls recruited patients underwent polysomnography cognitive studies microarray bioinformatics analysis performed using peripheral blood mononuclear cell samples identified b cellassociated genes significantly altered expression expression levels genes validated realtime pcr peripheral blood cell subsets examined flow cytometry putative correlations among clinical laboratory parameters investigated correlation network analysis sleep cognitive functions equally impaired bms nbms bms patients showed significantly reduced memory b cell increased regulatory b cell percentages nbms patients among genes selected bioinformatics levels blk blnk bank1 fcrl2 tgfb1 kcns3 genes significantly different among study subgroups correlation network analysis showed associations among physicalcognitive disability sleep dysfunction measures ms versus expression levels selected genes bms nbms differ physical disability cognitive sleep dysfunction different components disability ms associated peripheral blood b cell ratios b cell related gene expression levels thus likely altered b cell functions participate progression disability mspmid34020389 doi101016 jmsard2021103019,0.0
social cognition multiple sclerosis subtypes metaanalysis mult scler relat disord 2021 apr 24 52102973 doi 101016 jmsard2021102973 online ahead printabstractbackground multiple sclerosis ms immunemediated demyelinating disease disrupts several social cognitive abilities including theory mind tom facial emotion recognition fer unclear specific tom subcomponents including cognitive affective tom affected patients ms social cognitive abilities ms subtypesmethods search pubmed web science embase databases conducted june 2020 effect sizes calculated using hedges g randomeffects modelresults total 45 studies included relative health controls hcs patients ms subtypes including relapsingremitting ms rrms progressive ms exhibited impairments tom g 077 g 070 g 075 respectively cognitive tom g 072 g 083 g 073 respectively affective tom g 084 g 063 g 0 50 respectively fer g 062 g 053 g 107 respectively addition difference progressive primary ms secondary progressive ms overall tom cognitive tom affective tom fer compared patients rrms patients progressive ms showed difference overall tom cognitive tom affective tom serious defects fer g 057 conclusions quantitative results indicate patients ms subtypes differential impairment core aspects social cognitive processing including tom fer may help develop structured social cognitive interventions mspmid33962135 doi101016 jmsard2021102973,1.0
health professional redeployment crosstraining response covid19 pandemic healthc q 2021 jul 24 2 2732 doi 1012927 hcq202126550abstractthe onset covid19 pandemic march 2020 required hospitals respond quickly effectively ensure availability healthcare professionals care patients ottawa hospital ottawa used fivestep process ensure organizational readiness redeployment regulated health professionals necessary 1 define current scopes practice 2 obtain disciplinespecific input 3 develop strategies based literature review government dictates 4 identify potential duties 5 ensure support staff hospital management support plan readily implemented results discussed terms operational outcomes eg number type deployments staff experience outcomes positive led recommendations improved organizational readinesspmid34297660 doi1012927 hcq202126550,0.0
artificial intelligence neurodegenerative diseases review available tools focus machine learning techniques artif intell med 2021 jul 117102081 doi 101016 jartmed2021102081 epub 2021 apr 30abstractneurodegenerative diseases shown increasing incidence older population recent years significant amount research conducted characterize diseases computational methods particularly machine learning techniques now useful tools helping improving diagnosis well disease monitoring process paper provide indepth review existing computational approaches used whole neurodegenerative spectrum namely alzheimers parkinsons huntingtons diseases amyotrophic lateral sclerosis multiple system atrophy propose taxonomy specific clinical features existing computational methods provide detailed analysis various modalities decision systems employed disease identify present sleep disorders present various diseases represent important asset onset detection overview existing data set resources evaluation metrics finally identify current remaining open challenges discuss future perspectivespmid34127244 doi101016 jartmed2021102081,0.0
skin gut imprinted helper t cell subsets exhibit distinct functional phenotypes central nervous system autoimmunity nat immunol 2021 jun 7 doi 101038 s41590021009488 online ahead printabstractmultidimensional singlecell analyses t cells fueled debate whether extensive plasticity mixed priming helper t cell subsets vivo developed experimental framework probe idea site priming systemic immune compartment determinant helper t cellinduced immunopathology remote organs sitespecific vivo labeling antigenspecific t cells inguinal gut draining mesenteric m lymph nodes show cells mt cells isolated inflamed central nervous system cns model multiple sclerosis ms distinct cells cxcr6+ mt cells expressed p2rx7 notably mt cells infiltrated white matter cells also recruited gray matter therefore propose definition helper t cell subsets site priming may guide advanced understanding helper t cell biology health diseasepmid34099917 doi101038 s41590021009488,0.0
novel de novo trex1 mutation patient retinal vasculopathy cerebral leukoencephalopathy systemic manifestations mimicking demyelinating disease mult scler relat disord 2021 may 7 52103015 doi 101016 jmsard2021103015 online ahead printabstractretinal vasculopathy cerebral leukoencephalopathy systemic manifestations rvcls rare fatal autosomal dominant vasculopathy associated mutations trex1 gene one de novo case reported literature report longterm clinical radiological pathological presentation patient de novo novel mutation gene description clinical genetic imaging pathologic characteristics important better characterize rvcls prevent unnecessary interventions rvcls considered patients tumefactive brain lesions unresponsive immunotherapypmid34044261 doi101016 jmsard2021103015,1.0
costeffectiveness adding sativex spray spasticity care belgium using bootstrapping instead monte carlo simulation probabilistic sensitivity analyses eur j health econ 2021 apr 20 doi 101007 s10198021012851 online ahead printabstractbackground uncertainty modelbased costutility analyses commonly assessed probabilistic sensitivity analysis model parameters implemented distributions values sampled distributions monte carlo simulation bootstrapping alternative method requires fewer assumptions incorporates correlations model parametersmethods markov modelbased costutility analysis comparing oromucosal spray containing delta9tetrahidrocannabinol + cannabidiol sativex nabiximols plus standard care versus standard spasticity care alone management multiple sclerosis spasticity performed 5year time horizon belgian healthcare payer perspective probabilistic sensitivity analysis implemented using bootstrap approach ensure correlations present source clinical trial data incorporated uncertainty estimatesresults adding sativex spray standard care found dominate standard spasticity care alone cost savings 6 068 qualityadjusted life year gain 0145 per patient 5year analysis probability dominance increased 29 first year 94 fifth year probability qaly gains excess 99 years consideredconclusions adding sativex spray spasticity care found dominate standard spasticity care alone belgian healthcare setting study showed use bootstrapping techniques markov model probabilistic sensitivity analysis instead monte carlo simulations bootstrapping avoided need make distributional assumptions allowed incorporation correlating structures present original clinical trial data uncertainty assessmentpmid33880663 doi101007 s10198021012851,0.0
exome sequencing reveals novel rare variants iranian familial multiple sclerosis importance pold2 disease pathogenesis genomics 2021 jun 8s08887543 21 002251 doi 101016 jygeno202106008 online ahead printabstractthe prevalence familial multiple sclerosis fms increasing worldwide endorses heritability disease given many genome variations ethnicityspecific consanguineous marriage affect genetic diseases hereditary disease gene analysis among fms patients iran country high rates parental consanguinity highly effective finding mutations underlying disease pathogenesis examine rare genetic mutations selected three iranian fms cases 3 ms patients one generation performed whole exome sequencing identified homozygous rare missense variant pold2 p arg141cys rs372336011 molecular dynamics analysis showed reduced polar dehydration energy conformational changes pold2 mutant found heterozygote rare missense variant nbfp1 p gly487asp rs778806175 study revealed possible role novel rare variants fms molecular dynamic simulation provided initial evidence structural changes behind pold2 mutantpmid34116171 doi101016 jygeno202106008,0.0
ccr6ccl20 axis therapeutic target autoimmune diseases autoimmun rev 2021 may 7102846 doi 101016 jautrev2021102846 online ahead printabstractchemokine receptor ccr6 expressed various cells b cells immature dendritic cells innate lymphoid cells ilcs regulatory cd4 t cells th17 cells ccl20 known highaffinity ligand binds ccr6 drives ccr6+ cells migration tissues ccl20 mainly produced epithelial cells expression increased several folds inflammatory conditions genomewide association studies gwas patients inflammatory bowel disease ibd psoriasis ps rheumatoid arthritis ra multiple sclerosis ms showed strong correlation expression ccr6 disease severity shown disruption ccr6ccl20 interaction using antibodies antagonists prevents migration ccr6 expressing immune cells site inflammation reduces severity disease review discussed importance ccr6ccl20 axis ibd ps ra ms recent advances targeting ccr6ccl20 controlling autoimmune diseasespmid33971346 doi101016 jautrev2021102846,0.0
trend incidence prevalence daly multiple sclerosis middle east northern africa region compared global west europe iran#39 s corresponding values 19902017 retrieved global burden diseases data mult scler relat disord 2021 apr 20 52102949 doi 101016 jmsard2021102949 online ahead printabstractbackground multiple sclerosis ms common immune mediated disorder central nervous system cns study compares worldwide occurrence epidemiologic burden ms middle east northern africa mena region western europe 1990 2017methods study used data global burden disease gbd studies initially age agespecific values estimated values compared among mentioned areas addition changes sex distribution ms according incidence prevalence disabilityadjusted life years dalys calculated trend ms incidence also compared among mena region countriesresults according ms incidence per 100 000 populations 1990 2017 occurrence new cases decreased slightly world 07 065 western europe 255 250 except iran sharp rise 2 28 slow increase mena region 09 1 ms prevalence 1990 2017 ages stable world mena region except steady increase iran highest value western europe study determined agespecific incidence ms regions 1990 2017 although data showed different trend changes age groups regions group age 2529 years highest risk ms incidence based gender incidence prevalence daly ms regions higher femaleconclusion 1990 2017 western europe highest ms prevalence mena region relatively stable trend ms incidence particular iran ms incidence constantly increasing surpassed western europe since 2013pmid33894481 doi101016 jmsard2021102949,0.0
translation cross cultural adaptation construct validation arabic version frenchay activities index people multiple sclerosis physiother res int 2021 may 19e1909 doi 101002 pri1909 online ahead printabstractbackground purpose assessing functional status people multiple sclerosis pwms major role determining help patients reach optimal level living independently community frenchay activity index fai commonly used scale evaluate functional status rehabilitation research practice settings aim study translate fai standard arabic language process crosscultural adaptation explore internal consistency construct validity produced arabic version fai afai among sample arabicspeaking pwmsmethod english version fai translated arabic according published guidelines cronbachs used assess internal consistency afai principal factor analysis conducted explore construct validityresults hundred six subjects participated study afai acceptable internal consistency cronbachs 070 principal factor analysis revealed instrument four main factors domestic chore leisure hobbies work rather original three factors scalediscussion afai acceptable internal consistency validity afai provides essential information participation level instrumental activities daily living activities among pwms speaking arabic languagepmid34008919 doi101002 pri1909,0.0
multiple sclerosis hospitalizations among users oral diseasemodifying therapies mult scler relat disord 2021 apr 20 52102944 doi 101016 jmsard2021102944 online ahead printabstractbackground oral diseasemodifying therapies namely dimethyl fumarate fingolimod teriflunomide become standard treatments multiple sclerosis clinical trials demonstrated reduction annual relapse rate realworld data lacking particularly older adults objective study evaluate realworld effectiveness oral diseasemodifying therapies among individuals multiple sclerosismethods used optumtm clinformaticstm data mart large dataset representative commercially insured individuals united states conduct retrospective cohort study adult users three oral diseasemodifying therapies september 2010 september 2015 therapies interest included dimethyl fumarate teriflunomide fingolimod hospitalization multiple sclerosis approximation clinical trial endpoint relapse study outcome cox proportional hazards models built evaluate association demographic clinical factors multiple sclerosis hospitalization subgroup analysis performed individuals ages 55 years olderresults identified 1 823 318 1 156 users dimethyl fumarate teriflunomide fingolimod met inclusion criteria respectively rates hospitalizations multiple sclerosis low among 3 297 persons 1 041 ages 55+ 36 1 000 patientyears dimethyl fumarate 43 1 000 teriflunomide 45 1 000 fingolimod multiple sclerosis hospitalization associated therapy switching adjusted hazard ratio 221 95 confidence interval 157284 minority 144 110189 history relapse year preceding oral therapy initiation 525 389709 conclusion oral diseasemodifying therapies comparably effective outcome multiple sclerosis hospitalization even older adultspmid33894480 doi101016 jmsard2021102944,0.0
proinflammatory microrna mir155 influences fibrillar amyloid1 42 catabolism microglia glia 2021 mar 10 doi 101002 glia23988 online ahead printabstractmicroglia innate immune cells central nervous system adopt rapid functional changes response damage associated molecular patterns including aggregated amyloid found alzheimers disease ad micrornas mirnas posttranscriptional modulators influence timing magnitude microglia inflammatory responses downregulating expression inflammatory effectors recent studies implicate mir155 mirna known regulate inflammatory responses pathogenesis neurodegenerative disorders including multiple sclerosis als familial parkinsons disease ad work asked mir155 expression microglia modifies cellular behaviors response fibrillar a142 fa142 vitro hypothesized microglia mir155 expression impact internalization catabolism extracellular fa142 primary microglia stimulated lipopolysaccharide demonstrate fast upregulation mir155 followed delayed upregulation mir146a antiinflammatory mirna conditional overexpression mir155 microglia resulted significant upregulation mir146a conditional deletion mir155 promoted transit fa142 lowph compartments catabolism occurs mir155 overexpression decreases fa142 catabolism uptake fa142 across plasma membrane increased downregulation mir155 expression taken together results support hypothesis inflammatory signaling influences ability microglia catabolize fa142 interconnected mechanisms modulated mir155 understanding mirnas modulate ability microglia catabolize fa142 will elucidate role cellular players molecular crosstalk ad pathophysiologypmid33694209 doi101002 glia23988,0.0
registry patients multiple sclerosis covid19 infection saudi arabia mult scler relat disord 2021 may 7 52103004 doi 101016 jmsard2021103004 online ahead printabstractbackground outbreak coronavirus disease 2019 covid19 rapidly spread developed pandemic threatening global health patients multiple sclerosis ms autoimmune demyelinating inflammatory disease central nervous system cns predominantly treated immunomodulatory immunosuppressive diseasemodifying therapies dmts can increase risk infection therefore concern patients may higher risk covid19 response growing concerns neurologists patients study aimed determine prevalence severity possible complications covid19 infection patients ms saudi arabia sa methods prospective cohort study demographic clinical data obtained patients residing sa ms positive result covid19 per reverse transcriptionpolymerase chain reaction test viral gene sequencing using respiratory plasma samples comparison covid19 severity groups performed using oneway anova kruskalwallis test numerical variables chisquared test categorical variablesresults seventy patients ms covid19 71 female included analysis 53 757 patients receiving dmt time covid19 infection frequently used dmts fingolimod 25 interferonbeta 25 nine 13 patients ms relapse treated intravenous methylprednisolone four weeks covid19 infection common symptoms peak covid19 infection fever 46 fatigue 37 headache 36 symptoms lasted mean duration 87 days symptomatic patients recovered deaths reported covid19 severity categorized three groups asymptomatic n 12 mildnot requiring hospitalization n 48 requiring hospitalization n 10 two admitted intensive care unit icu three groups comparison age body mass index expanded disability severity score ms disease duration dmt use time infection showed significant differences higher percentage patients admitted hospital icu 40 p 0026 presented ms relapse within prior four weeks compared asymptomatic mild infection 83 conclusion findings present reassuring picture regarding covid19 infection patients ms however patients ms relapse preceding four weeks requiring glucocorticoid treatment may increased risk severe covid19pmid34049217 doi101016 jmsard2021103004,1.0
gut microbiome research multiple sclerosis neurosci res 2021 may 11s01680102 21 000973 doi 101016 jneures202105001 online ahead printabstractrecent studies identified specific gut microbial species linked various human diseases gutbrain axis currently attracting much attention field microbiome science clinically biologically research multiple sclerosis ms mouse model experimental autoimmune encephalomyelitis one active research subjects notably recent achievements established bidirectional causality ms gut microbiome reduction gut microbiomederived short chain fatty acids enrichment gutassociated oxidative stress appear promoting neurodegenerative processes also researchers trying elucidate mechanisms microbiome regulates onset progression ms new findings achieved analysis causal relationship ms gut microbiome will provide new therapeutic strategy ms results will contribute understanding cause prevention treatment ms will lead complete cure disease future ms curative treatment yet established unmet needs may overcome analysis gut microbiomepmid33989681 doi101016 jneures202105001,0.0
covid19 vaccines multiple sclerosis treated cladribine ocrelizumab mult scler relat disord 2021 may 4 52102983 doi 101016 jmsard2021102983 online ahead printabstractsince recent approval vaccines covid19 efficacy concerns emerged ms patients treated immunosuppressive drugs report experience four patients cladribine two ocrelizumab two treatment low lymphocyte count three vaccinated 3 months last dose good immune response one ocrelizumab 2 months without developing appropriate title antibodies experience suggests discriminant response vaccine lymphocyte count timing vaccinationpmid33990054 doi101016 jmsard2021102983,0.0
natalizumab early relapsingremitting multiple sclerosis 4year openlabel study adv ther 2021 may 20 doi 101007 s1232502101722w online ahead printabstractintroduction strive 4year multicenter observational openlabel singlearm study natalizumab treatment antijc virus antibodynegative jcvnegative relapsingremitting multiple sclerosis rrms patients disease duration 3 years objective strive examine evidence disease activity neda status predictors neda natalizumabtreated patients early rrmsmethods proportions patients neda evaluated along baseline predictors neda annualized relapse rate 24week confirmed disability worsening cdw magnetic resonance imaging assessments t2 gadoliniumenhancing lesions serious adverse eventsresults years 1 2 561 95 confidence interval ci 487634 736 95 ci 662802 patients intenttotreat population n 222 respectively achieved neda years 3 4 846 95 ci 780899 919 95 ci 864958 patients respectively achieved clinical neda relapses 24week cdw baseline predictors neda year 4 expanded disability status scale score 20 odds ratio 385 95 ci 154963 p 0004 t2 lesion volume 4 cc 039 95 ci 015098 p 0046 latter also predicting clinical neda year 4 021 95 ci 005092 p 0038 cumulative probability cdw year 4 193 serious adverse events reported 113 patientsconclusion results support longterm safety effectiveness natalizumab baseline predictors neda help inform benefitrisk assessments natalizumab treatment jcvnegative patients early rrmstrial registration clinicaltrialsgov identifier nct01485003pmid34014549 doi101007 s1232502101722w,0.0
role microbiotaderived shortchain fatty acids nervous system disorders biomed pharmacother 2021 jul 139111661 doi 101016 jbiopha2021111661 epub 2021 may 8abstractduring past decade accumulating evidence research highlights suggested effects bacterial communities human gut microbiota metabolites health disease regard microbiotaderived metabolites receptors beyond immune system maintain metabolism homeostasis essential maintain hosts health balancing utilization intake nutrients shown gut bacterial dysbiosis can cause pathology altered bacterial metabolites formation resulting dysregulation immune system metabolism shortchain fatty acids scfas butyrate acetate succinate produced due fermentation process bacteria gut noted remodeling gut microbiota metabolites associated pathophysiology several neurological disorders alzheimers disease multiple sclerosis parkinsons disease amyotrophic lateral sclerosis stress anxiety depression autism vascular dementia schizophrenia stroke neuromyelitis optica spectrum disorders among others review will discuss current evidence significant studies dealing scfas gut microbial metabolism selected neurological disorderspmid34243604 doi101016 jbiopha2021111661,0.0
course covid19 infection patients multiple sclerosisthe experience one center based population upper silesia mult scler relat disord 2021 apr 28 52102984 doi 101016 jmsard2021102984 online ahead printabstractbackground suspected patients multiple sclerosis ms greater risk severe acute respiratory syndrome coronavirus 2 sarscov2 infection due disability immunotherapy relationship ms coronavirus disease 2019 covid19 uncertain aim study collect analyze relationshipmethods ms patients neurological outpatient clinic zabrze poland regularly questioned symptoms covid19 contact infected person patients presented covid19 symptoms confirmed contact infected person referred covid19 test patients confirmed sarscov2 infection n 41 included analysis medical records study group analyzed patient condition monitored outpatient clinic recovery 26 subjects additional examinations including brain magnetic resonance imaging mri electroneurography eng electroencephalography eeg color duplex doppler cdd visual evoked potentials veps brainstem auditory evoked potentials baeps psychological assessment performed following recoveryresults one patient required hospitalization covid19 infection whereas 8780 patients require treatment covid19 patients creactive protein crp levels 10 mg l 244 patients oxygen partial pressure 95 ms patients results examinations covid19 infection similar prior infection psychological assessment revealed anxiety found 4231 patientsconclusions mild course covid19 ms patients seems common despite diseasemodifying drug treatment disability selfisolation recommended reduce number infected patients covid19 infection worsen course ms subjects patients ms may require additional psychological support pandemic due susceptibility anxietypmid34000683 doi101016 jmsard2021102984,0.0
immunization multiple sclerosis childhood immunemediated disorders central nervous system review literature eur j paediatr neurol 2021 jun 17 33125134 doi 101016 jejpn202106002 online ahead printabstractchildhood period vaccines administered order buildup immunological memory immunization vaccinepreventable diseases essential part child care health administration vaccines children inflammatory diseases frequent point concern parents physicians published information relation vaccines autoinflammatory diseases central nervous system cns consists case cohort studies reviews great majority adult patients vaccines established causative triggering effects diseases another issue immunization schedule patients autoinflammatory cns diseases specifically interactions disorder clinical status treatment vaccine review summarize existing information autoinflammatory disorders cns vaccines childhood underline points considered various treatment regimenspmid34214824 doi101016 jejpn202106002,0.0
enhancing mood cognition quality life pediatric multiple sclerosis paediatr drugs 2021 may 17 doi 101007 s40272021004515 online ahead printabstractpediatriconset multiple sclerosis poms representing approximately 5 ms cases affects central nervous system ongoing development poms commonly diagnosed adolescence can occur younger children well pediatric patients ms critical manage full impact disease monitor effects school social functioning disease management includes diseasemodifying therapies also strategies optimize wellbeing review interventions highest evidence ability improve disease course quality life poms high levels vitamin d diet low saturated fat associated lower relapse rates exercise ameliorates fatigue sleep behavioral strategies sleep hygiene mood regulation can also improve fatigue perceived health poms management addressed holistically including assessing overall symptom burden well psychological functional impact diseasepmid33997945 doi101007 s40272021004515,0.0
realworld singlecentre analysis alemtuzumab cladribine multiple sclerosis mult scler relat disord 2021 apr 11 52102945 doi 101016 jmsard2021102945 online ahead printabstractbackground highly active ms may warrant higher efficacy treatments disease control however often confer risk compared headtohead clinical trials making relative efficacy safety difficult interpret alemtuzumab cladribine two highefficacy treatments given discrete courses separated one year followed durable response potentially require ongoing treatment approval oral cladribine centre treating patients bioequivalent intravenous iv regimen since 2010 objective study report safety efficacy data alemtuzumab cladribine realworld single centre settingmethods retrospectively reviewed patients treated alemtuzumab cladribine ottawa hospital ms clinic 2 years followup information baseline demographic variables previous treatment prior disease activity collected outcomes investigated evidence disease activity neda constituents new clinical relapse new mri activity expanded disability status scale edss progression well adverse events treatment discontinuation performed univariate multiple logistic regression determine differences 2year neda timetoevent analyses cox regression models determine factors associated outcome study periodresults fortysix patients treated alemtuzumab 65 cladribine 51 78 received intravenous regimen followed total 4201 personyears cladribine group older p0002 higher baseline edss p0015 likely secondary progressive p0001 alemtuzumab higher rate 2year neda cladribine 478 95ci 1571450 p006 beyond 2 years difference statistically significant hr 050 95ci 0251 30 p061 prior treatments associated lower likelihood retaining neda hr 126 95ci 103154 p027 alemtuzumab infusion reactions 80 vs 17 p0001 shingles 22 vs 2 p005 secondary autoimmunity 52 vs 3 p0001 cladribine difference grade 3 higher adverse events 217 vs 185 p10 conclusion cohort alemtuzumab cladribine achieved similar rates neda longterm followup overall less adverse events cladribine patient registries allow robust comparisons detection adverse events assessment durable responsepmid33901969 doi101016 jmsard2021102945,0.0
association bladder dysfunction balance falls women multiple sclerosis specific contribution fear falling gait posture 2021 jun 10 88252257 doi 101016 jgaitpost202106010 online ahead printabstractbackground bladder dysfunction common autonomic disturbance people ms pwms studies examined relationship bladder dysfunction falls pwms bladder dysfunction deemed secondary outcome measure classified gross measure providing limited perspective disturbing symptom furthermore study date focused relationship bladder dysfunction balance performance pwmsresearch question determine relationship bladder dysfunction balance falls fear falling women msmethods study observational including 44 women ms mean age 463 sd 57 least mild bladder dysfunction outcome measures included urinary incontinence quality life scale iqol bladder control scale blcs timed go test tug four square step test fsst falls efficacy scale international fesi falls status posturographyresults participants performed tug 141 s sd 111 fsst 205 s sd 224 relatively large proportion 682 women classified fallers however differences found classified fallers n 30 nonfallers n 14 terms iqol blcs controlling age edss number vaginal deliveries significant correlations scores found iqol blcs fesi rho 047 controlling age edss number vaginal deliveries associations demonstrated bladder dysfunction outcome scores either tug fsstsignificance women afflicted ms suffering bladder dysfunction tend fall present balance difficulties compared disabilitymatched pwms nevertheless bladder dysfunction detected perceived severity condition associated balance prevalence falling rather fear fallingpmid34130094 doi101016 jgaitpost202106010,0.0
effects oxygenozone therapy regulatory tcell responses multiple sclerosis patients cell biol int 2021 mar 16 doi 101002 cbin11589 online ahead printabstractmultiple sclerosis ms common degenerative disorder central nervous system decreased frequency dysfunction treg cell cause inflammation disease progression ozone autohemotherapy can used potential therapeutic approach regulate immune system responses inflammation ms purpose 20 relapsingremitting multiple sclerosis rrms patients treatment ozone twice weekly six months frequency treg cell expression levels treg cellrelated factors foxp3 il10 tgf mir17 mir27 mir146a secretion levels il10 tgf assessed found significant increase number treg cell expression levels foxp3 mirnas mir17 mir27 il10 tgf factors patients oxygenozone o2o3 therapy compared treatment contrast oxygenozone therapy notably decreased expression level mir146a treated patients interestingly secretion levels il10 tgf cytokines considerably increased serum supernatant cultured pbmcs posttreatment condition compared pretreatment condition according results oxygenozone therapy raised frequency treg cell relevant factors treated ms patients oxygenozone therapy contributed improving ms patients elevating treg cell responses article protected copyright rights reservedpmid33724614 doi101002 cbin11589,0.0
temporal trends incidence prevalence multiple sclerosis northwest spain mult scler relat disord 2021 apr 24 52102979 doi 101016 jmsard2021102979 online ahead printabstractbackground last decades frequency multiple sclerosis ms increasing worldwide nevertheless higher sensibility new diagnostic criteria obscures comparison studies performed different decadesmethods evolution frequency ms santiago de compostela northwest spain 2003 2015 analyzed using poisson regression diagnosis confirmed according poser criteria several sources consulted case ascertainment databases ms unit infusion center departments neurology pharmacy pediatric neurology codification public hospital santiago private hospitals neurologists private activity general practitioners associations patientsresults 12 years prevalence increased 68 143 cases 100 000 inhabitants 83 176 females 49 106 males p 00001 00001 00002 respectively incidence rise significant 5 8 cases 100 000 inhabitants year p04243 mean age population growth 57 years p0008 changes female male ratio 129 age first symptom 22 years diagnosis delay 012 years achieve significance p07750 01606 08581 conclusion prevalence ms doubled 12 years whilst difference incidence lower significant disproportion growth parameters well higher mean age last study suggest longer survival patients mspmid33964571 doi101016 jmsard2021102979,0.0
altered distributions circulating follicular helper follicular regulatory t cells accountable imbalanced cytokine production multiple sclerosis clin exp immunol 2021 mar 24 doi 101111 cei13596 online ahead printabstractfollicular t helper tfh regulatory tfr cells distinct subsets cd4+ t lymphocytes regulating humoral immune responses germinal center widely accepted dysregulated tfh tfr cells associated autoimmunity evaluated frequencies circulating cxcr5+ pd1+ tfh ctfh cxcr5+ pd1+ foxp3+ cd25+ tfr ctfr cells corresponding cytokines peripheral blood mononuclear cells 28 patients relapsingremitting multiple sclerosis ms 16 age sexmatched healthy controls hc subsets ctfh cells th1 th17 related surface markers cxcr3 ccr6 also evaluated found frequency ctfh cells significantly higher ms patients compared hc conversely frequency ctfr cells lower ms patients hc il21 producing ctfh cells significantly increased ms patients il10 secreting ctfr cells lower ms compared levels hc among ctfh cells ctfh171 cells major subtypes significantly increased ms compared hc frequency il21 secreting cells highest results suggest imbalanced distribution ctfh ctfr exist ms contributes reciprocally altered il21 il10 productionpmid33759187 doi101111 cei13596,0.0
exploring role multiple sclerosis susceptibility gene clec16a t cells scand j immunol 2021 jul 94 1 e13050 doi 101111 sji13050 epub 2021 may 20abstractctype lectinlike domain family 16 member clec16a associated autoimmune disorders including multiple sclerosis ms functional relevance completely understood clec16a expressed several immune cells affects autophagic processes receptor expression recently reported risk genotype msassociated single nucleotide polymorphism clec16a intron 19 associated higher expression clec16a cd4+ t cells show clec16a expression induced cd4+ t cells upon t cell activation use imaging flow cytometry confocal microscopy demonstrate clec16a located rab4apositive recycling endosomes jurkat tag t cells clec16a knockdown jurkat cells resulted lower cell surface expression t cell receptor however major impact t cell activation response vitro jurkat human primary cd4+ t cellspmid34643957 doi101111 sji13050,0.0
natalizumab differentially affects plasmablasts b cells multiple sclerosis mult scler relat disord 2021 may 1 52102987 doi 101016 jmsard2021102987 online ahead printabstractbackground natalizumab treatment increases frequencies b cells blood reduces igg blood csf plasmablasts important production igg development plasmablasts cd49d dependentobjective hypothesized natalizumab treatment affects development plasmablastsmethods retrospectively analyzed frequencies absolute counts b cell subsets flow cytometry longitudinal cohort 9 progressive multiple sclerosis ms patients treated natalizumab 60 weeks crosssectional relapsingremitting ms rrms cohort 17 untreated 37 treated natalizumab 17 stable 20 unstable patients relapse activity additionally cd49d expression b cell subsets examined 10 healthy controls blood cerebrospinal fluid csf frequencies b cell subsets quantified untreated natalizumab treated rrms patientsresults progressive ms levels igg decreased plasma p0001 baseline 60 weeks followup progressive ms rrms cohorts observed natalizumab treatment significantly increased frequency b cells p0004 p00001 several b cell subsets pronounced memory b cell subsets p00001 p00001 decrease plasmablast frequency p0008 p0008 progressive ms rrms absolute cell counts b cells increased p0004 p0001 explained significant increase subsets except plasmablasts furthermore found decreased memory b cell counts unstable compared stable natalizumabtreated patients p002 expression cd49d higher plasmablasts compared b cell subsets p00001 csf plasmablasts detected patients treated natalizumab contrast increased frequency untreated rrms patientsconclusion confirm previous studies showing natalizumab increases circulating number b cells particularly memory cells concomitant decrease plasma igg concentrations moreover demonstrate two separate cohorts natalizumab treatment markedly decreases frequencies plasmablasts absolute number stable additionally plasmablasts high expression cd49d plasmablasts detected csf natalizumabtreated patients finally memory b cells found reduced unstable natalizumabtreated patients possibly indicate increased recruitment cnspmid33984651 doi101016 jmsard2021102987,0.0
correction multiple sclerosis switching natalizumab highefficacy treatments mitigate progressive multifocal leukoencephalopathy risk neurotherapeutics 2021 nov 2 doi 101007 s1331102101148w online ahead printno abstractpmid34729691 doi101007 s1331102101148w,0.0
association multiple sclerosis disease severity adherence diseasemodifying therapies j manag care spec pharm 2021 jul 27 7 915923 doi 1018553 jmcp2021277915abstractbackground multiple sclerosis ms patients taking diseasemodifying therapies dmts adherence treatment key component achieving beneficial outcomes delayed disease progression reduction prevention symptoms relapses objectives aim study assess impact claimsbased measure ms disease severity dmt adherence oneyear study period methods patients identified humana medicare advantage claims data january 1 2013 december 31 2015 patients age 18 least 12 months continuous enrollment 1 outpatient ms visit dmt use prior index date included patients switched dmt type oral platform iv study period excluded medication possession ratios mpr dmts calculated pharmacy medical claims 12 months claims data previously developed claims algorithm used determine ms disease severity patients mprs 08 higher considered adherent dmt treatment multivariable logistic regression used evaluate association ms disease severity gender dmt type age category dmt adherence results study population 3 347 patients average mpr 847 75 classified adherent multivariable logistic analysis demonstrated compared 1845 age group 4664 65+ age groups 133 133 95 ci 108164 155 155 95 ci 118205 times likely adherent patients high level ms disease severity 53 047 95 ci 036062 less likely adherent compared low ms disease severity significant difference identified gender dmt type oral platform iv conclusions increased age lower ms disease severity associated better dmt adherence ms disease severity considered assessing risk low dmt adherence disclosures funding supported project authors nothing disclose preliminary results previously presented virtually amcp annual 2020 april 2020pmid34185555 doi1018553 jmcp2021277915,0.0
bibliometric analysis multiple sclerosis nursing research based web science ann palliat med 2021 jul 10 7 75517559 doi 1021037 apm211057abstractbackground bibliometric analysis widely used gauge scholarly impact scientific publication conducted give basic overview research publications multiple sclerosis nursingmethods publications multiple sclerosis nursing retrieved using bibliometric method based web science database 19002018 results total 825 papers collected 49 countries retrieved study number publications multiple sclerosis nursing increased steadily since 1999 top 12 research institutions publishing articles nine ten prolific authors united states articles frequently published journal neuroscience nursing key words top 10 highly cited papers changed quality life qol symptoms terms including social support psychological problems rehabilitation treatment cognitive impairment nursing intervention nursing practice neuroscience nursing focus research topics included qol functional rehabilitation symptom management nursing intervention support schemesconclusions research multiple sclerosis nursing china early stage greater attention research focus results top institutions core journals focus highly cited papers needed advance fieldpmid34353043 doi1021037 apm211057,0.0
pulmonary embolism patients multiple sclerosis treated teriflunomide series three cases clin neurol neurosurg 2021 may 15 206106685 doi 101016 jclineuro2021106685 online ahead printabstractteriflunomide oral disease modifying therapy patients relapsing remitting multiple sclerosis moderately effective favourable safety profile liver toxicity major concern present series three patients developed pulmonary embolism within two years initiation teriflunomide treatment stable multiple sclerosis low level disability immobility presenting negligible risk development pulmonary embolism estimated prevalence pulmonary embolism cohort 28 thus believe additional attention general risk factors pe warranted teriflunomide introduced patients multiple sclerosispmid34020325 doi101016 jclineuro2021106685,0.0
attenuation antibody response sarscov2 infection patients multiple sclerosis ocrelizumab casecontrol study mult scler relat disord 2021 may 7 52103014 doi 101016 jmsard2021103014 online ahead printabstractobjective ocrelizumab ocr monoclonal antibody directed bcells fda approved treatment rrms ppms prior studies raised concerns patients ability form antibodies response various antigens especially sarscov2 objective study determine whether ocr attenuates antibody response sarscov2 patients ms compared disease modifying therapiesmethods casecontrol study looking odds developing antibodies sarscov2 patients treated ocr versus disease modifying therapies may 13 2020 march 1 2021 patients rtpcrconfirmed infection sarscov2 tested presence antibodies data recorded outpatients ms methodist hospitals comprehensive ms center selected prior infection covid19 demonstrated rtpcr electronic health records odds ratios calculated compare rates antibody formation ocr exposure vs dmtresults 24 patients evidence covid19 antibody testing available time analysis patients received ocr decreased odds forming antibodies 0045 p 0011 95 ci 0004 0488 conclusions patients received ocr within prior 6 months covid19 infection decreased odds developing antibodies compared dmts suggests ocr may attenuate antibody response sarscov2 additional studies analyze odds spike protein antibody formation response sarscov2 vaccines patients ocrpmid34000684 doi101016 jmsard2021103014,0.0
interferons multiple sclerosis lessons 25 years clinical realworld experience intramuscular interferon beta1a avonex cns drugs 2021 jul 6 doi 101007 s4026302100822z online ahead printabstractrecombinant interferon ifn 1b approved us food drug administration first diseasemodifying therapy dmt multiple sclerosis ms 1993 since time clinical trials realworld observational studies demonstrated effectiveness ifn therapies pivotal intramuscular ifn 1a phase iii trial published 1996 first demonstrate dmt reduce accumulation sustained disability ms patient adherence treatment higher intramuscular ifn 1a given weekly subcutaneous formulations requiring multiple injections per week moreover subcutaneous ifn 1a associated increased incidence injectionsite reactions neutralizing antibodies compared intramuscular administration recent years revisions ms diagnostic criteria improved clinicians ability identify patients ms promoted use magnetic resonance imaging mri diagnosis disease monitoring mri studies show treatment ifn 1a relative placebo reduces t2 gadoliniumenhancing lesions gray matter atrophy since approval intramuscular ifn 1a number highefficacy therapies approved ms though benefit highefficacy therapies balanced increased risk serious adverse events associated longterm use subpopulations patients including pregnant women safety profile ifn formulations may provide particular benefit addition antiviral properties ifns may indicate potential therapeutic opportunities ifn reducing risk viral infections covid19pmid34228301 doi101007 s4026302100822z,0.0
enhanced frontoparietal connectivity multiple sclerosis patients healthy controls response intensive computerized training focused working memory mult scler relat disord 2021 apr 24 52102976 doi 101016 jmsard2021102976 online ahead printabstractbackground working memory wm deficits common multiple sclerosis ms patients computerized cognitive training may enhance wm capabilities efficacy ms patients sufficiently exploredmethods study examines effects nback training cognitive performance functional connectivity fc 29 ms patients 29 healthy controls hc baseline s1 performance 2 3back tasks fc within frontoparietal network assessed randomly splitting sample four subgroups trained ms mst n 15 trained hc hct n 14 untrained ms msu n 14 untrained hc hcu n 15 trained subgroups underwent adaptive nback training 60 min day 4 days nback task performance fc reassessed second session s2 results revealed mixed twoway anovas trained participants mst hct exhibited significant increase number correct responses significantly reduced reaction times s2 performance improvements accompanied increase fc frontoparietal pathways statistically significant correlations effects foundconclusions computerised wm training results behavioural neuroplasticity positive effects may useful trying prevent attenuate cognitive decline ms patientspmid33964569 doi101016 jmsard2021102976,0.0
milestone multiple sclerosis therapy monoclonal antibodies cd20yet progress continues neurotherapeutics 2021 apr 20 doi 101007 s1331102101048z online ahead printabstractmultiple sclerosis ms chronic inflammatory disease central nervous system still represents one common causes persisting disability early disease onset growing evidence suggests b cells play crucial role pathogenesis progression last decades monoclonal antibodies mabs surface protein cd20 intensively studied b cell targeting therapy relapsing ms rms well primary progressive ms ppms pivotal studies anticd20 therapy rms showed remarkable clinical radiological effects especially acute inflammation relapse biology results paved way research implication b cells pathogenesis ms besides controlling relapse development rms ocrelizumab ocr also showed clinical benefits patients ppms became first approved drug disease course review provide overview current anticd20 mabs used tested treatment msnamely rituximab rtx ocr ofatumumab ofa ublituximab ub besides effectiveness also discuss possible limitations safety concerns especially regard longterm treatment class drugs overall well anticd20 mab individually additionally elucidate extent anticd20 therapy may alter function immune cells directly indirectly finally cover current knowledge repopulation cd20+ cells cessation anticd20 treatment discuss future aspirations towards alternative developed b cell silencing therapiespmid33880738 doi101007 s1331102101048z,0.0
effects hippotherapy postural balance functional mobility selfperceived fatigue quality life people relapsingremitting multiple sclerosis secondary results exploratory clinical trial mult scler relat disord 2021 apr 20 52102948 doi 101016 jmsard2021102948 online ahead printabstractbackground multiple sclerosis ms results worsening postural balance functional mobility selfperceived fatigue influences quality lifeobjective examine effects hippotherapy postural balance functional mobility selfperceived fatigue quality life people msmethods participants assigned hippotherapy intervention group n 17 control group n 16 intervention included 16 sessions 30minutes hippotherapy conducted twice week whereas control group maintained therapeutic routine postural balance evaluated cop speed cm s cop 95 elliptical area cm2 using force platform 4 experimental conditions stable surface eyes open stable surface eyes closed foam surface eyes open foam surface eyes closed functional mobility evaluated timed go tug test fatigue severity scale fss modified fatigue impact scale mfis measured perceived fatigue functional assessment multiple sclerosis fams measured quality life data examined using mixed model anova bonferroni post hocresults cop speed cop 95 elliptical area p 05 significantly decreased across testing conditions intervention group compared control tug improved time intervention group p 001 fss p 001 addition also improvement score mfis domains p 005 intervention group compared control fams improved time intervention group p 05 conclusion hippotherapy improved postural balance functional mobility fatigue quality life people relapsingremitting ms suggests hippotherapy may useful approach complimentary treatment among people mspmid33940496 doi101016 jmsard2021102948,0.0
outcome national mscovid19 study turkish ms cohort reveals mult scler relat disord 2021 apr 18 52102968 doi 101016 jmsard2021102968 online ahead printabstractbackground pandemic new type corona virus infection 2019 covid19 also affect people multiple sclerosis pwms currently accumulating information effects infection regarding demographic clinical characteristics disease well outcomes within different dmts enable us better practices management covid19 infection pwmsobjective investigate incidence coronavirus disease 2019 covid19 reveal relationship demographicclinical therapeutic features outcome covid19 infection multicenter national cohort pwmsmethods turkish neurological societyms study group association italian musc19 study group initiated study webbased electronic case report form ecrf studymusc19 used collect data demographic data ms histories patients obtained file tracking forms relevant clinicsresults 309 ms patients confirmed covid19 infection included study two hundred nineteen 219 females 709 mean age 369 ranging 18 66 194 628 40 clinical phenotype relapsingremitting 277 896 progressive 32 104 disease duration ranged 02 years 314 years median edss 15 ranging 0 85 edss score 1 134 43 patients 916 patients dmt fingolimod frequently used drug 220 followed interferon 201 comorbidity rate 117 able detect significant association dmts covid19 severityconclusion turkish mscovid19 cohort confirmed pwms risk severe covid19 outcome irrespective dmt treated addition due younger population less comorbidities mild disease highlight associated risk factors moderate severe covid19 course similar general population comorbid conditions olderpmid33940495 doi101016 jmsard2021102968,0.0
autologous hematopoietic stem cell transplantation multiple sclerosis global approval availability review bone marrow transplant 2021 apr 6 doi 101038 s4140902101276z online ahead printno abstractpmid33824434 doi101038 s4140902101276z,0.0
efficacy safety ocrelizumab vs interferon beta1a participants african descent relapsing multiple sclerosis phase iii opera opera ii studies mult scler relat disord 2021 may 7 52103010 doi 101016 jmsard2021103010 online ahead printabstractbackground people african descent multiple sclerosis ms appear severe disease course may attenuated response medications compared people european descentmethods post hoc subgroup analysis participants african descent relapsing forms ms enrolled phase iii opera opera ii clinical trials treated ocrelizumab ocr 600 mg every 6 months interferon beta1a ifn 1a 44 g 3 times per weekresults among 1 656 participants enrolled opera ii 72 43 african descent ocr 40 ifn 1a 32 trend reduction annualized relapse rate arr observed participants african descent 50 reduction ocr vs ifn 1a relative rate mean number gadoliniumenhancing lesions magnetic resonance imaging mri 004 95 ci 001022 p0001 participants african descent treated ocr compared ifn 1a similarly relative rate number new enlarging t2 lesions mri 014 95 ci 006032 p0001 participants african descent treated ocr 261 times likely received ifn 1a classified evidence disease activity 95 ci 124549 p0003 417 times likely classified evidence disease activity progression 95 ci 1271365 p0006 africandescent participants tended greater radiographic burden disease baseline develop brain lesions treated ifn 1a greater risk disability progression nonafricandescent participants participants african descent experienced slightly adverse events serious adverse events hypersensitivity reactions nonafricandescent participantsconclusion small sample participants african descent relapsing ms opera studies ocr demonstrated treatment benefits clinical mri composite efficacy outcomes vs ifn 1a consistent observed complete opera intentiontotreat cohortspmid34147885 doi101016 jmsard2021103010,0.0
economic burden multiple sclerosis low middleincome countries systematic review pharmacoeconomics 2021 may 6 doi 101007 s40273021010327 online ahead printabstractbackground although economic burden multiple sclerosis ms highincome countries hics extensively studied information costs ms low middleincome countries lmics remains scarce moreover review synthesizing assessing costs ms lmics yet undertakenobjective objective systematically identify review cost illness coi ms lmics critically appraise methodologies used compare cost estimates across countries level disease severity examine cost driversmethods conducted systematic literature search original studies english french dutch containing prevalence incidencebased cost data ms lmics search conducted medline ovid pubmed embase ovid cochrane library national health service economic evaluation database nhs eed econlit cinahl ebsco july 2020 without restrictions publication date recommended validated methods used data extraction analysis make results coi studies comparable costs adjusted us year 2019 values using world bank purchasing power parity inflated using consumer price indexresults total 14 studies identified conducted uppermiddleincome economies eight studies used bottomup approach costing six used topdown approach four studies used societal perspective total annual cost per patient ranged us463 58 616 costs varied across studies countries mainly differences regarding inclusion costs diseasemodifying therapies dmts range cost items included methodological choices approaches used estimate healthcare resource consumption inclusion informal care productivity losses characteristics methodologies included studies varied considerably especially regarding perspective adopted cost data specification reporting costs per severity levels total costs increased greater disease severity cost ratios different levels ms severity within studies relatively stable costs around 115 times higher moderate versus mild ms two times higher severe versus mild ms ms drug costs main cost driver less severe ms whereas proportion direct nonmedical costs indirect costs increased greater disease severityconclusion ms places huge economic burden healthcare systems societies lmics methodological differences substantial variations terms absolute costs found studies made comparison studies challenging however cost ratios across different levels ms severity similar making comparisons studies disease severity feasible cost drivers mainly dmts relapse treatments consistent across studies yet distribution cost components varied disease severitypmid33956330 doi101007 s40273021010327,0.0
anticd20 antibody therapy risk infection patients demyelinating diseases mult scler relat disord 2021 may 1 52102988 doi 101016 jmsard2021102988 online ahead printabstractbackground anticd20 antibody therapy may associated increased risk infections therefore investigated risk factors infection patients demyelinating diseases treated anticd20 antibody therapymethods retrospective uncontrolled study patients ever treated anticd20 antibodies academic clinic identified danish multiple sclerosis registry dmsr data collected medical charts dmsr assessed occurrence severe infections requiring hospitalization varicella zoster virus vzv major comorbidities routine laboratory values lymphocytes igg igmresults total 447 patients ever treated anticd20 antibody therapy identified 416 649 patient years followup still therapy group seven patients vzv infections 16 patients hospitalized infections three years followup anticd20 therapy comorbidity recorded 80 patients risk severe infection associated comorbidities higher age longer duration treatment higher expanded disability status scale edss scores multivariable analyses treatment duration edss scores presence comorbidity independently associated risk severe infections serum concentrations igg igm decreased increasing duration therapy associated risk severe infections patients vzv infection lower lymphocyte counts lower serum concentrations igm multivariable analyses lymphocyte counts independently associated risk vzv infectionconclusions retrospective study patients treated anticd20 antibodies risk infections requiring hospitalization independently associated comorbidities duration treatment higher edss scores risk vzv infection independently associated lymphopenia future studies investigating strategies mitigating risk infection patients treated anticd20 antibodies warranted especially older patients patients higher levels disability patients longer duration treatmentpmid33979772 doi101016 jmsard2021102988,1.0
aggressive multiple sclerosis argentina data nationwide registry relevarem j clin neurosci 2021 jun 1s09675868 21 002654 doi 101016 jjocn202105047 online ahead printabstractthe objectives present study describe frequency aggressive multiple sclerosis ams well compare clinical radiological characteristics ams nonams patients included relevarem nct03375177 methods eligible study population cohort selection included adultonset patients 18 years definite ms ams defined reaching confirmed edss 6 within 5 years symptom onset confirmation achieved subsequent edss 6 recorded least six months later within 5 years first clinical presentation ams nonams compared using 2 test categorical mannwhitney continuous variables ms onset multivariable analysis performed using forward stepwise logistic regression baseline characteristics disease onsetresults total 2158 patients ms included 74 ams 2084 nonams prevalence ams cohort 34 95ci 2742 ams likely male p 0003 older ms onset p 0001 primary progressive ms ppms phenotype p 003 multifocal presentation p 0001 spinal cord well infratentorial lesions mri disease onset p 0004 p 0002 respectively conclusion 34 patient population considered ams men patients older symptom onset multifocal presentation ppms phenotype spinal cord well brainstem lesions mri clinical presentation higher odds amspmid34088579 doi101016 jjocn202105047,0.0
discovery kv 13 ion channel inhibitors medicinal chemistry approaches challenges med res rev 2021 may 1 doi 101002 med21800 online ahead printabstractthe kv 13 voltagegated potassium ion channel involved many physiological processes plasma membrane mitochondria chiefly immune nervous systems therapeutic targeting kv 13 specific peptides small molecule inhibitors shows great potential treating cancers autoimmune diseases multiple sclerosis type diabetes mellitus psoriasis contact dermatitis rheumatoid arthritis myasthenia gravis however kv 13targeted compounds approved therapeutic use date review focuses presentation approaches discovering new kv 13 peptide smallmolecule inhibitors strategies improve selectivity active compounds toward kv 13 selectivity dalatazide shk186 synthetic derivate sea anemone toxin shk achieved chemical modification successfully reached clinical trials potential therapeutic treating autoimmune diseases peptides smallmolecule inhibitors critically evaluated leadlike characteristics potential progression clinical development smallmolecule inhibitors welldefined structureactivity relationships optimized selective delivery mitochondria offer therapeutic potential treatment cancers overview kv 13 inhibitors methodologies designed provide good starting point drug discovery identify novel effective kv 13 modulators target futurepmid33932253 doi101002 med21800,0.0
interleukin1 receptor antagonist exploratory plasma biomarker correlates disabilty provides pathophysiological insights relapsingremitting multiple sclerosis mult scler relat disord 2021 may 7 52103006 doi 101016 jmsard2021103006 online ahead printabstractbackground multiple sclerosis ms chronic inflammatory demyelinating neurodegenerative disorder interleukin1 receptor antagonist il1ra endogenous soluble antagonist il1 receptor blocks proinflammatory effects il1 known contribute ms pathology objectives study determine whether il1ra associated disability ms correlates neurofilament light nfl levels cerebrospinal fluid csf methods peripheral blood csf collected consenting ms patients patient demographic clinical variables including past relapse activity also collected circulating levels il1ra il18 il1 measured plasma il1ra nfl measured csf via bioplex multiplex immunoassay kits elisa respectively il1ra expression investigated vitro using primary human macrophages microglia situ using postmortem ms tissueresults following multiple regression analysis il1ra levels plasma correlated expanded disability status scale score independent variables separate cohort csf il1ra significantly correlated nfl vitro induction nlrp3 inflammasome pathological hallmark within ms lesions led increased release il1ra primary human microglia macrophages cns il1ra+ macrophages microglia present rim mixed active inactive ms lesionsconclusions results presented study demonstrate il1ra novel exploratory biomarker relapsingremitting ms correlates disability provides mechanistic insights regulatory inflammatory responses within demyelinated cnspmid34004435 doi101016 jmsard2021103006,1.0
depression anxiety multiple sclerosis patients role genetic variability interleukin 1beta mult scler relat disord 2021 apr 30 52102982 doi 101016 jmsard2021102982 online ahead printabstractbackground mood disorders depression anxiety frequent multiple sclerosis ms patients high proinflammatory cytokine levels eg il1 reported depressed individualsobjective aimed investigate role rs16944 il1511 ct polymorphism development anxiety depression symptoms portuguese cohort ms patientsmethods 393 ms patients answered hospital anxiety depression scale hads t1 questionnaire reapplied subgroup 175 ms patients approximately three years later t2 hads cutoff scores anxiety depression respectively 11 8results t1 anxiety found 106 ms patients 270 11 controls 167 whereas depression identified 116 295 ms patients 9 controls 136 persistent anxiety depression respectively recorded 12 20 ms patients rs16944tt genotype found susceptibility factor occurrence depression t1 316 p0002 development persistent depression 563 p0003 msconclusion study results support hypothesis inflammation significant factor psychopathology developmentpmid34004436 doi101016 jmsard2021102982,0.0
manipulating oligodendrocyte intrinsic regeneration mechanism promote remyelination cell mol life sci 2021 may 21 doi 101007 s00018021038524 online ahead printabstractin demyelinated lesions astrocytes activated microglia infiltrating macrophages secrete several factors regulating oligodendrocyte precursor cells behaviour appears initiation intrinsic mechanism myelin repair leading partial recovery inefficient remyelination process worsening course disease failure largely due concomitant accumulation inhibitory cues around lesion sites opposing growth promoting factors starts complex game interactions signalling pathways controlling oligodendrocytes migration differentiation receptors positive negative cues modulating ras pi3k rhogtpases pathways acting oligodendrocyte cytoskeleton remodelling description intricate signalling network review addresses extent modulation global response inhibitory cues may pave route towards novel therapeutic approaches myelin repairpmid34019104 doi101007 s00018021038524,1.0
systematic review possible interactions herbal medicines dietary supplements used concomitantly diseasemodifying symptomalleviating multiple sclerosis drugs phytother res 2021 feb 24 doi 101002 ptr7050 online ahead printabstractmultiple sclerosis ms demyelinating disease affecting central nervous system curative medicine available use herbal drugs dietary supplements increasing among people ms pwms raising need knowledge potential interactions conventional ms medicine herbal drugs dietary supplements systematic review provides information safety simultaneous use conventional msdrugs herbal drugs frequently used pwms study included 14 selected diseasemodifying treatments drugs frequently used symptomalleviation total 129 published papers found via pubmed web science reviewed according defined inclusion exclusion criteria findings suggested daily recommended doses panax ginseng ginkgo biloba exceeded herbal preparations differing standardized products avoided especially combined anticoagulants substrates certain cytochrome p450 isoforms studies required regarding ginsengs ability increase aspirin bioavailability combinations chronic cannabis use selective serotonin reuptake inhibitors nonsteroidal antiinflammatory drugs carefully monitored whereas significant evidence druginteractions conventional msdrugs ginger cranberry vitamin d fatty acids turmeric probiotics glucosamine foundpmid33624893 doi101002 ptr7050,1.0
reactivation sarscov2 rituximab patient multiple sclerosis mult scler relat disord 2021 mar 25 52102922 doi 101016 jmsard2021102922 online ahead printabstracta 32yearold woman highly active ms infected sarscov2 treatment rituximab recovered symptomfree 21 days receiving rituximab ivig comorbid hypogammaglobulinemia three days infusion redeveloped respiratory symptoms required admission three sarscov2 nasopharyngeal swabs antibody testing negative however bronchial alveolar lavage detected sarscov2 reactivation sarscov2 rituximab ms reported known risk conditions timing anticd20 treatment sarscov2 infection requires investigation individual consideration reduce risk reactivationpmid33895693 doi101016 jmsard2021102922,0.0
populationbased study association autoimmune disease lymphoma national health insurance servicenational sample cohort 20022015 korea j autoimmun 2021 may 12 121102647 doi 101016 jjaut2021102647 online ahead printabstractbackground aimed evaluate association autoimmune disease aid lymphoma incidence korean population also aimed compare overall survival os patients aidassociated lymphoma aal patients lymphoma without aidmaterial methods used national sample cohort 20022015 provided national health insurance service among 1 011 638 patients 994 496 recruited final cohort 130 987 patients 132 aid group 863 509 868 control lymphoma diagnosed 1162 patients 322 patients accompanying aid irrespective time point diagnosis defined aal patients experienced lymphoma development least one year aid diagnosis defined postaid lymphoma n 155 results median followup duration 137 years aal accounted 003 total 277 lymphoma cases aid patients experienced epsteinbarr virus 002 vs 001 p 0027 helicobacter pylori infection 639 vs 414 p 0001 control group aid associated 145fold increased risk lymphoma median time interval aid aal 109 months risk lymphoma increased order psoriasis adjusted odds ratio aor 161 systemic lupus erythematosus aor 399 multiple sclerosis aor 452 sarcoidosis aor 2637 sjogren syndrome related lymphoma cohort 5year os aal different lymphoma patients without aid 609 vs 615 p 0970 conclusions association patterns aal korean population different western countries studies lymphomatogenesis distinct baseline characteristics eg chronic infection status elucidate difference based race ethnicitypmid33991884 doi101016 jjaut2021102647,0.0
crosssectional analysis peripheral blood mononuclear cells lymphopenic nonlymphopenic relapsingremitting multiple sclerosis patients treated dimethyl fumarate mult scler relat disord 2021 may 7 52103003 doi 101016 jmsard2021103003 online ahead printabstractbackground relapsingremitting multiple sclerosis rrms autoimmune disorder central nervous system dimethyl fumarate diseasemodifying medication used treat rrms patients can induce lymphopenia aimed immunophenotype peripheral blood mononuclear cells pbmc rrms patients crosssectionally examine characteristics modifications lymphopenia timemethods characterization pbmc done multiparametric flow cytometry patients treatment 4 years grouped lymphopenic dmfl nonlymphopenic dmfn patientsresults lymphopenia affected cell population changes time patient characteristics gender age previous treatment status also significant effects lymphopenic nonlymphopenic patients pbmc percentages reduced time overall t b cells frequencies affected males older patients untreated patients significant changes b cell subpopulations time cd4+ cd8+t cell ratio increased significantly lymphopenic patients time cd4cd8t cell population similarly reduced lymphopenic nonlymphopenic patients time monocyte nk overall populations changed nonclassical monocyte subpopulation decreased time lymphopenic patients also found cd56cd16+ cd56cd16 nk cells frequencies changed time lymphopenic patients immune populations showed correlations clinical outcomes measured edss relapse rate analysis overall immunophenotype showed groups divided patient characteristics showed differences lymphopenia status overrode differences resulting similar immunophenotype within dmflconclusions data provide evidence therapy lymphopenia affects immunophenotype changes time can override differences associated patient characteristics possibly mask significant changes immune profile patientspmid34118574 doi101016 jmsard2021103003,0.0
thalamic nuclei degeneration multiple sclerosis j clin neurosci 2021 jun 2s09675868 21 002617 doi 101016 jjocn202105043 online ahead printabstractobjectives define severity extent structural alteration certain thalamic nuclei means mr morphometry compare findings clinical performance different phenotypes multiple sclerosis ms methods comparatively measured thalamus nuclei volumes patients remittingrelapsing rrms secondaryprogressive spms phenotypes multiple sclerosis healthy control subjects hc evaluation neurological performance based results expanded disability status scale multiple sclerosis severity scale cognitive mental state rated according results minimental state examination frontal assessment battery montreal cognitive assessment symbol digit modalities test freesurfer 60 used thalamic nuclei volumes calculationresults median volume decline thalamic pulvinar nuclei rrms group left side anterior nucleus 186 6 mm3 posterior nucleus 149 4 mm3 medial nucleus 852 4 mm3 compared hc anterior nucleus 229 2 mm3 posterior nucleus 187 5 mm3 medical nucleus 1081 3 mm3 group right side anterior nucleus 219 5 mm3 posterior nucleus 187 1 mm3 medial nucleus 989 6 mm3 hc group anterior nucleus 261 1 mm3 posterior nucleus 240 5 mm3 medial nucleus 1196 7 mm3 p 0 05 highest correlation written section sdmt observed left ventral anterior nucleus r 0 71 conclusion findings indicate credible correlation clinical progression neurological cognitive impairment ms patients asymmetry leftsided thalamic nuclei atrophy may considered potential predicting tool ms progressionpmid34090763 doi101016 jjocn202105043,0.0
fatty acidbinding protein fabp decreases clinical signs modulates immune responses mouse model experimental autoimmune encephalomyelitis eae int immunopharmacol 2021 may 13 96107756 doi 101016 jintimp2021107756 online ahead printabstractbackground increasing body studies shown fasciola hepatica can affect immune responses study explored whether fatty acidbinding protein fabp f hepatica can modulate immune system mouse model experimental autoimmune encephalomyelitis eae methods eaeinduced c57bl 6 mice treated vehicle f hepatica total extract te fabp clinical signs body weights expression ifn tbet il4 gata3 il17 ror tgf foxp3 il10 tnf genes proteins determined isolated cd4+ splenocytes besides percentage treg cells degree demyelination evaluatedresults found te fabp treatments decreased clinical scores lymphocyte infiltration rate demyelinated plaques eae mice expressions il4 gata3 increased whereas il17 tnf downregulated fabp affect expression ifn ror il10 tgf genes proteins reduced expression tbet te administration affect expression il10 tbet genes increased expression levels ifn foxp3 cd4+ lymphocytes fabp te treatment affect treg cell percentageconclusion study indicates f hepatica fabp te can suppress inflammatory responses eaeinduced mice shift immune system toward th2 responses however fabp exerts stronger antiinflammatory effects seems effective te eae treatmentpmid33993100 doi101016 jintimp2021107756,1.0
effectiveness group hope therapy training quality life meaning life patients multiple sclerosis family caregivers iran j psychiatry 2021 jul 16 3 260270 doi 1018502 ijpsv16i36251abstractobjective multiple sclerosis chronic progressive neurological disease due special nature various physical mental influences patients familys lives decreasing quality life threatening meaning life purpose present study evaluate effectiveness group hope therapy training quality meaning life patients multiple sclerosis family caregivers method quasiexperimental study performed using pretestposttest control group thirty patients multiple sclerosis along 30 family caregivers got low medium scores meaning life questionnaire steger mlq multiple sclerosis impact scale msis29 iranian quality life questionnaire irqol caregivers selected purposively patients randomly divided two groups 15 individuals experimental 15 individuals control groups caregivers grouped manner protocol group hope therapy training carried eight twohour sessions two weeks separately two experimental groups patients caregivers finally posttest given four experimental control groups results results data showed meaning life patient caregiver experimental groups increased significantly p 0001 significant change patient caregiver control groups conclusion group hope therapy training effective intervention improving meaning life quality life patients multiple sclerosis also psychological intervention aims improve quality life patients advanced stage disease requires attention physical mental issues time although group hope therapy training improved meaning life patients significant impact quality life therefore paying attention stages multiple sclerosis physical condition patients therapeutic intervention adopting necessary complementary interventions seems essentialpmid34616459 pmcpmc8452831 doi1018502 ijpsv16i36251,0.0
data augmentation using generative adversarial neural networks brain structural connectivity multiple sclerosis comput methods programs biomed 2021 apr 24 206106113 doi 101016 jcmpb2021106113 online ahead printabstractbackground objective machine learning frameworks demonstrated potentials dealing complex data structures achieving remarkable results many areas including brain imaging however large collection data needed train models particularly challenging biomedical domain since due acquisition accessibility costs pathology related variability available datasets limited usually imbalanced overcome challenge generative models can used generate new datamethods study framework based generative adversarial network proposed create synthetic structural brain networks multiple sclerosis ms dataset consists 29 relapsingremitting 19 secondaryprogressive ms patients t1 diffusion tensor imaging dti acquisitions used obtain structural brain network subject evaluation quality newly generated brain networks performed analysing structural properties ii studying impact classification performanceresults demonstrate advanced generative models directly applied structural brain networks quantitatively qualitatively show newly generated data present significant differences compared real ones addition augmenting existing dataset generated samples leads improvement classification performance f1score 81 respect baseline approach f1score 66 conclusions approach defines new tool biomedical application connectomebased data augmentation needed providing valid alternative usual imagebased data augmentation techniquespmid34004501 doi101016 jcmpb2021106113,0.0
therapeutic potential novel glucagonlike peptide1 receptor agonist nly01 experimental autoimmune encephalomyelitis neurotherapeutics 2021 jul 14 doi 101007 s13311021010885 online ahead printabstractmultiple sclerosis ms chronic inflammatory disease central nervous system cns characterized demyelination gliosis neurodegeneration currently available diseasemodifying therapies effectively suppress immune attack cns therapies date directly mitigate neurodegeneration glucagonlike peptide1 glp1 small peptide hormone maintains glucose homeostasis novel glp1 receptor glp1r agonist nly01 recently shown neuroprotective effects animal models parkinsons disease now phase 2 clinical trial study investigated therapeutic potential nly01 mouse model ms experimental autoimmune encephalomyelitis eae data show nly01 delays onset attenuates severity eae prevention paradigm given disease onset nly01 inhibits activation immune cells spleen reduces trafficking cns addition show nly01 suppresses production chemokines involved leukocyte recruitment site inflammation antiinflammatory effect nly01 early stage eae may block expression genes associated neurotoxic astrocytes optic nerves thereby preventing retinal ganglion cell rgc loss progressive stage eae therapeutic paradigm nly01 significantly decreases clinical score second attack model relapsingremitting eae glp1r agonists may dual efficacy ms suppressing peripheral cns inflammation thereby limiting neuronal losspmid34260042 doi101007 s13311021010885,1.0
development impact cladribine lymphoid myeloid cells multiple sclerosis mult scler relat disord 2021 apr 15 52102962 doi 101016 jmsard2021102962 online ahead printabstractcladribine approved selective immune reconstitution therapy relapsingremitting ms rrms first developed used treat various forms cancer particularly leukemia via parenteral administration oral tablet version cladribine later developed treat rrms autoimmune disorder central nervous system cns periods relapse remission cladribine found selectively deplete adaptive immune cell types role innate immune cells largely unknown among lymphocyte populations subtypes magnitude kinetics depletion cladribine vary substantially current consensus selective cytotoxic effect cladribine dependent deoxycytidine kinase dck 5nucleotidase 5nt ratio immune cell type nonetheless discrepancies fully elucidated dck5nt ratio paradigm review aims delineate development pharmacological properties cladribine elucidate influence lymphoid myeloid cells mspmid33901971 doi101016 jmsard2021102962,0.0
postural stability valid meaningful disability metric progressive ms potential use neuroprotective therapy trials mult scler relat disord 2021 apr 11 52102946 doi 101016 jmsard2021102946 online ahead printabstractbackground balance impairment observed 70 people ms pwms worsens disease progression posturography using force platform current gold standard measurement balance however posturography adequately studied widely accepted use disability outcome measure pwms importantly recent emergence successful failed neuroprotective therapy trials progressive ms emphasised need new disability outcome measures people progressive ms main objectives study evaluate clinical validity reliability feasibility posturography disability metric progressive msmethods prospective crosssectional study recruited 73 people progressive ms age 1865 years edss 3560 participants stood centre force platform feet comfortably apart various conditions eyes open eo ii eyes closed ec single task lasting ninety seconds simultaneous eo cognitive test iii nback threeminute test whereby participants instructed click mouse two identical letters displayed consecutively screen iv sustained attention response task fiveminute test whereby participants instructed click mouse every number 1 9 except 3 ie dualtasks additionally performed battery validated physical cognitive outcome measures posturographic data processed using matlab statistical analysis performed using spss version 26 used multiple linear regression modelling determine whether significant univariate correlations posturography clinical metrics independent covariates may influence associations seen twotailed significance level 005 usedresults 73 participants mean age 524 85 years mean ms disease duration 138 103 years median edss 50 iqr 4060 44 604 female eopathlength independently predicted upper extremity function 9holepegtest larger effect size adjusted r2200 p 0001 walking measures timed 25foot walk adjusted r216 p 001 twominute walk test adjusted r272 p 0002 controlling age disease duration height weight sex addition eomediolateraldisplacement ms functional composite msfc created fourcomponent zscore increased variance explained quality life qol 621 postural stability significantly lower mediolateral vs anteroposterior direction sway removal vision increased body weight male sex fampridine use postural stability improved dualtasks compared eo single task posturography detected significant worsening balance single prolonged stanceconclusion postural stability independently predicted wide range clinical metrics including upper extremity function walking ability cognition qol therefore establishing construct concurrent validity disability outcome measure people progressive ms additionally posturography quantitative noninvasive quickandeasytoadminister highly sensitive device demonstrating high feasibility use time resourceefficient disability metric neuroprotective therapy trials progressive mspmid33901968 doi101016 jmsard2021102946,1.0
modified models distinguish central nervous system demyelinating diseases brain lesions mult scler relat disord 2021 apr 17 52102965 doi 101016 jmsard2021102965 online ahead printabstractbackground brain lesions patients myelin oligodendrocyte glycoprotein antibodyassociated disease mogad indistinguishable relapsingremitting multiple sclerosis rrms aquaporin4 antibodypositive neuromyelitis optica spectrum disorder aqp4ab nmosd methods patients mogad rrms aqp4ab nmosd abnormal brain lesions retrospectively reviewed divided training validation sets discriminatory models using brain images demographics generated identify optimal predictors using orthogonal partial least square discriminant analysis principal component analysis pca clinicoradiological data without diagnosis constructed models tested independent cohortresults pca 51 brain scans demographics patients 13 mogad 24 rrms 14 aqp4ab nmosd demonstrated rrms distinct antibodymediated conditions best predictors mogad aqp4ab nmosd poorly demarcated lesions large abnormalities predictive mogad female sex disease duration linear lesions adjacent lateral ventricle cerebellum involvement predictive mogad periventricular ovoid round juxtacortical callosal lesions dawsons fingers t1 hypointensity predictive rrms fluffy well large lesions mogad best predictors mogad rrms rrms versus mogad rrms versus aqp4ab nmosd models exhibited high predictive value perfect accuracy 100 validated independent cohort model patients aqp4ab nmosd mogad exhibited lower predictive power still achieved accuracy 90conclusions brain mri characteristics combined demographics enables distinction mogad rrms aqp4ab nmosd fluffy large lesions relatively specific mri characteristics patients mogad brain abnormalities asian countriespmid33905981 doi101016 jmsard2021102965,1.0
socioeconomic status access multiple sclerosis treatment mexico mult scler relat disord 2021 apr 20 52102967 doi 101016 jmsard2021102967 online ahead printabstractintroduction multiple sclerosis ms chronic neurological autoimmune condition leading nontraumatic cause neurological disability worldwide diseasemodifying therapies dmt directly impact longterm prognosis patients ms preventing relapses associated disability progression analyzed impact socioeconomic status ses dmt access mexican patientsmethods evaluated association ses dmt access using ms registry national institute neurology neurosurgery mexico city included 974 patients ms mcdonald 2010 criteria categorized ses according 2018 mexican association market research agencies amai ses classification analyzed dmt type ms phenotype educational level symptomatic onset diagnosis edss arrival well progression index chisquared wilcoxon tests used multivariable analysis performed dmt accessresults comparing lower versus higher levels ses significant association found percentage patients higher levels disability edss 6 arrival proportion patients receiving dmt higher proportion secondary progressive ms p0006 p0001and p0004 respectively also found lower educational levels significance inverse association edss first visit p0019 symptomatic onset diagnosis p0001 higher disability status arrival edss 6 p0010 conclusions study suggests ses important factor determining prompt overall access highly effective dmt lower ses associated greater levels disability first clinic visit higher proportion patients receiving dmt 12 months followuppmid33934010 doi101016 jmsard2021102967,0.0
antilingo1 improved remyelination neurobehavioral deficit cuprizoneinduced demyelination iran j basic med sci 2021 jul 24 7 900907 doi 1022038 ijbms20215353112043abstractobjectives central nervous system demyelination main feature multiple sclerosis ms important unmet need ms use treatments delay progression disease leucinerich repeat immunoglobulinlike domain containing nogo receptorinteracting protein 1 lingo1 known inhibitors oligodendrocyte differentiation myelinationmaterials methods investigated lingo1 antibody effects remyelination neurobehavioral deficit using cuprizoneinduced demyelination animals randomly divided three groups n 10 1 control group received regular diet 2 cpz group normal saline injected intraperitoneally 3 treatment group lingo1 antibody 10 mg kg injected ip every six days 3 weeks assessed level myelin basic protein mbp neurofilament heavy chain nf200 brainderived neuroprotective factor bdnf corpus callosum cc immunostaining mbp nf200 bdnfresults found decreased levels mbp nf200 bdnf demyelinated cc antilingo1 treatment improved demyelinated structures furthermore motor impairment measured openfield oft balance beam tests treatment group motor impairment significantly improvedconclusion results provide evidence lingo1 antibody can improve remyelination neurobehavioral deficitpmid34712419 pmcpmc8528247 doi1022038 ijbms20215353112043,1.0
cd52targeted depletion alemtuzumab ameliorates allergic airway hyperreactivity lung inflammation mucosal immunol 2021 mar 17 doi 101038 s41385021003885 online ahead printabstractallergic asthma chronic inflammatory disorder associated airway hyperreactivity ahr whose global prevalence increasing alarming rate group 2 innate lymphoid cells ilc2s t helper 2 th2 cells producers type 2 cytokines may contribute development ahr study explore potential cd52targeted depletion type 2 immune cells treating allergic ahr show anticd52 therapy can prevent remarkably reverse established il33induced ahr reducing airway resistance alleviating lung inflammation show cd52 depletion prevents treats allergic ahr induced clinically relevant allergens alternaria alternata house dust mite importantly leverage various humanized mice models ahr show new therapeutic applications alemtuzumab anticd52 depleting antibody currently fda approved treatment multiple sclerosis results demonstrate cd52 depletion viable therapeutic option reduction pulmonary inflammation abrogation eosinophilia improvement lung function thus treatment allergic ahr taken together data suggest anticd52 depleting monoclonal antibodies alemtuzumab can serve viable therapeutic drugs amelioration th2 ilc2dependent ahrpmid33731828 doi101038 s41385021003885,0.0
possible direct correlation cognitive impairment fear catching covid19 among patients multiple sclerosis iran j psychiatry 2021 jul 16 3 336342 doi 1018502 ijpsv16i36260abstractobjective prevalence cognitive impairment multiple sclerosis ms significant estimated 40 70 patients ms suffer impairment covid19 also new infectious disease symptoms disease include fever shortness breath cough can mild severe can even lead death due use immunosuppressive drugs patients ms might greater risk catching covid19 thus patients ms may afraid catching virus one important factors relationship cognitive deficit increase patients fear covid19 aim study assess relationship fear catching covid19 cognitive impairment patients ms method crosssectional study conducted ms clinic sina hospital tehran university medical sciences tehran iran participants project patients ms 18 years old history neurological psychiatric diseases addition obtaining demographic clinical information measured fear catching covid 2019 via fear covid19 scale fcv19s 7item questionnaire also used multiple sclerosis neuro psychological screening questionnaire msnq assess memory information processing speed patients ms results adjustment age gender disease duration highest level education ms type edss linear regression model well msnq total score fear score catching coronavirus results demonstrated significant positive correlation p value 000 0024 conclusion present study showed direct relationship cognitive disorder level fear regarding covid19 patients cognitive disorders afraid covid19pmid34616468 pmcpmc8452838 doi1018502 ijpsv16i36260,0.0
sapropterin bh4 aggravates autoimmune encephalomyelitis mice neurotherapeutics 2021 apr 12 doi 101007 s13311021010434 online ahead printabstractdepletion enzyme cofactor tetrahydrobiopterin bh4 tcells shown prevent proliferation upon receptor stimulation models allergic inflammation mice suggesting bh4 drives autoimmunity hence clinically available bh4 drug sapropterin might increase risk autoimmune diseases present study assessed implications multiple sclerosis ms exemplary cns autoimmune disease plasma levels biopterin persistently low ms patients tended lower high expanded disability status scale edss instead bypass product neopterin increased deregulation suggested bh4 replenishment might drive immune response beneficially restore bh4 balances answer question mice treated sapropterin immunizationevoked autoimmune encephalomyelitis eae model multiple sclerosis sapropterintreated mice higher eae disease scores associated higher numbers tcells infiltrating spinal cord normal tcell subpopulations spleen blood mechanistically sapropterin treatment associated increased plasma levels longchain ceramides low levels polyunsaturated fatty acid linolenic acid fa183 lipid changes known contribute disruptions bloodbrain barrier eae mice indeed rna data analyses revealed upregulations genes involved ceramide synthesis brain endothelial cells eae mice lass6 cers6 lass3 cers3 ugcg elovl6 elovl4 results support view bh4 fortifies autoimmune cns disease mechanistically involving lipid deregulations known contribute eae pathologypmid33844153 doi101007 s13311021010434,0.0
artificial intelligence extension oscarib criteria ann clin transl neurol 2021 may 19 doi 101002 acn351320 online ahead printabstractartificial intelligence ai based diagnostic algorithms achieved ambitious aims automated image pattern recognition neurological disorders includes neurodegeneration inflammation scalable imaging technology big data neurology optical coherence tomography oct highlight oct changes observed retina window brain small requiring rigorous quality control pipelines existing tools purpose firstly humanled validated consensus quality control criteria oscarib oct secondly criteria embedded oct reporting guidelines apostel use described annotation failed oct scans advances machine learning illustrated present review advantages disadvantages aibased applications oct data neurological conditions reviewed use big data include alzheimer disease stroke multiple sclerosis ms parkinson disease epilepsy noted big data relevant ai ownership complex reason also reached involve representatives patient organizations public domain addition clinical research centers evidence reviewed can grouped fivepoint expansion oscarib criteria embrace ai oscarai review concludes specific recommendations can achieved practically compliance existing guidelinespmid34008926 doi101002 acn351320,0.0
tanshinone iia phytochemical promising drug candidate neurodegenerative diseases pharmacol res 2021 may 7105661 doi 101016 jphrs2021105661 online ahead printabstracttanshinones lipophilic diterpenes isolated rhizome salvia miltiorrhiza diverse pharmacological activities human ailments including neurological diseases fact tanshinones used treat heart diseases stroke vascular diseases traditional chinese medicine last decade tanshinones widely studied phytochemicals neuroprotective effects experimental models cerebral ischemia alzheimers diseases importantly tanshinone iia mostly studied tanshinone biological activities recently reported attenuate bloodbrain barrier permeability among stroke patients suggesting tanshinone iia appealing therapeutic candidate neurological diseases tanshinone iia also effective experimental models parkinsons disease multiple sclerosis neuroinflammatory diseases addition several experimental studies suggested pleiotropic neuroprotective effects antiinflammatory antioxidant antiapoptotic bbb protectant value aiding tanshinone appealing therapeutic strategy neurological diseases therefore review aimed compile recent updates cellular molecular mechanisms neuroprotection tanshinone iia diverse neurological diseasespmid33971269 doi101016 jphrs2021105661,1.0
matchingadjusted indirect treatment comparison ozanimod versus teriflunomide relapsing multiple sclerosis mult scler relat disord 2021 apr 25 52102972 doi 101016 jmsard2021102972 online ahead printabstractbackground growing number immunomodulating diseasemodifying therapies available treatment relapsing multiple sclerosis rms absence randomized headtohead trials matchingadjusted indirect comparisons maics can used adjust crosstrial differences evaluate comparative efficacy safety agents used maic methodology indirectly compare key outcomes ozanimod ozm teriflunomide teri treatment rmsmethods systematic literature review conducted identify clinical trials evaluating efficacy safety ozm vs teri given absence headtohead trials ozm vs teri used matchingadjusted indirect comparison adjust potential treatment effect modifiers prognostic factors assessing confirmed disability progression cdp relapse safety outcomes individual patient data ozm sunbeam radiance part b trials aggregate level data teri asclepios ii tower optimum temso trials used evaluate following outcomes annualized relapse rate arr proportion patients relapsed cdp 3 6 months overall adverse events aes serious aes saes discontinuations due aesresults matching baseline patient characteristics balanced ozm teri compared teri ozm demonstrated significant improvements arr rate ratio 073 95 ci 062084 proportion patients relapsed odds ratio 056 95 ci 044070 overall aes 035 95 ci 029043 saes 053 95 ci 037077 discontinuations due aes 014 95 ci 009021 ozm demonstrated statistically significant improvements cdp 3 months hazard ratio hr 078 95 ci 066092 nonsignificant differences 6 months hr 078 95 ci 060101 compared tericonclusion indirect treatment comparison patients rms ozm appeared improved benefitrisk profile teripmid33979770 doi101016 jmsard2021102972,0.0
natalizumab discontinuation dutch realworld cohort mult scler relat disord 2021 apr 24 52102974 doi 101016 jmsard2021102974 online ahead printabstractobjective determine characteristics multiple sclerosis patients discontinued natalizumab treatment realworld cohortmethods data collected ongoing observational cohort study natalizumab treated patients amsterdam umcresults 253 patients ever received natalizumab treatment 147 discontinued treatment frequent reason treatment discontinuation jcvirus jcv positivityconclusions jcv positivity seems frequent reason natalizumab discontinuation heterogeneity treatment switches reflects advances made treatment options underlines need adequate patient counsellingpmid33990055 doi101016 jmsard2021102974,0.0
progressive myelopathy myelin oligodendrocyte glycoprotein antibodyassociated disease new mimicker progressive multiple sclerosis mult scler relat disord 2021 apr 20 52102964 doi 101016 jmsard2021102964 online ahead printabstractbackground mogiggassociated disease mogad adults typically presents monophasic relapsing optic spinal opticospinal neuroinflammatory syndrome current recommendations discourage testing mogigg patients clinical paraclinical findings typical ms patients progressive clinical course however approach may impede identification full phenotypic spectrum recently described disorder methods retrospectively reviewed charts 39 mogiggseropositive patients two ohiobased neuroimmunology centers identify unusual disease patterns progressive course included case series results describe five cases progressive myelopathy associated mogigg patients features suggestive ms including typical mri cerebrospinal fluid findings however mogigg positive patients progressive myelopathy showed poor response ms disease modifying therapy better response intravenous immunoglobulins similar previous reports mogad patients conclusion mogiggseropositive patients may present progressive myelopathy may clinical radiologic phenotype suggestive primary progressive secondary progressive ms progressive solitary sclerosis mogigg testing considered patients progressive myelopathy especially clinically worsening ms therapypmid33915519 doi101016 jmsard2021102964,1.0
correction natalizumab early relapsingremitting multiple sclerosis 4year openlabel study adv ther 2021 jun 22 doi 101007 s12325021018156 online ahead printno abstractpmid34159559 doi101007 s12325021018156,0.0
specific blockade bone morphogenetic protein2 4 induces oligodendrogenesis remyelination demyelinating disorders neurotherapeutics 2021 jun 22 doi 101007 s13311021010689 online ahead printabstractoligodendrocyte precursor cells opcs present demyelinated lesions multiple sclerosis ms patients however differentiation functional oligodendrocytes insufficient lesions evolve nonfunctional astroglial scars blockade bone morphogenetic protein bmp signaling induces differentiation opcs myelinproducing oligodendrocytes studied effect specific blockade bmp2 4 signaling intravenous iv treatment antibmp2 4 neutralizing mab inflammatory model relapsing experimental autoimmune encephalomyelitis reae cuprizonetoxic model demyelination mice administration antibmp2 4 reaeinduced mice day 9 postimmunization pi ameliorated reae signs diminished expression phosphosmad1 5 8 primarily within astrocytic lineage increased numbers de novo immature mature oligodendrocytes reduced numbers newly generated astrocytes within spinal cord early day 18 pi effect accompanied elevated remyelination manifested increased density remyelinating axons 08 gratios 1 reduced fully demyelinated demyelinating axons antibmp2 4treated reae mice studied electron microscopy significant immunosuppressive effect observed cns periphery peak first attack end experiment moreover iv treatment antibmp2 4 mab cuprizonechallenged mice augmented numbers mature oligodendrocytes remyelination corpus callosum recovery phase disease based findings specific blockade bmp2 4 therapeutic potential demyelinating disorders ms inducing early oligodendrogenesismediated remyelination affected tissuepmid34159538 doi101007 s13311021010689,1.0
association diseasemodifying therapies prescribed persons multiple sclerosis cancer pharmacovigilance database analysis neurotherapeutics 2021 jul 6 doi 101007 s1331102101073y online ahead printabstractthe risk cancer associated persons multiple sclerosis pwms prescribed disease modifying therapies dmts well established observational crosssectional pharmacovigilance cohort study examined individual case safety reports world health organization database vigibase consecutive reports dmts prescribed pwms alemtuzumab dimethyl fumarate fingolimod glatiramer acetate interferon natalizumab ocrelizumab teriflunomide serious adverse event cases eligible excluding reporting immunosuppressant dmts used anticancer therapies primary outcome multivariate odds ratio cancer reporting ror dmts prescribed pwms imputation missing data 5966 cancer cases 240 993 reports dmts prescribed pwms adjustments age sex geographical region natalizumab ror 174 95 ci 163187 interferon ror 139 95 ci 130149 dimethyl fumarate ror 135 95 ci 125146 fingolimod ror 115 95 ci 106124 significantly associated greater cancer reporting whereas alemtuzumab glatiramer acetate ocrelizumab teriflunomide disproportionality analysis exploratory analyses upper aerodigestive tract breast urinary including male genitourinary tract nervous system cancers associated natalizumab interferon dimethyl fumarate fingolimod associated skin cancer types cancer cases reporting four dmts prescribed pwms younger age nonpwms drugs vigibase p 00001 close regular cancer screening pwms treated natalizumab interferon dimethyl fumarate fingolimod may warranted even persons younger age trial registration nct04237337pmid34231126 doi101007 s1331102101073y,0.0
fear relapse social support psychological wellbeing depression anxiety stress level patients multiple sclerosis ms covid19 pandemic stage neurol sci 2021 apr 15 doi 101007 s10072021052538 online ahead printabstractbackground psychological wellbeing assessment covid19 pandemic essential patients multiple sclerosis ms goal study evaluate fear relapse social support psychological wellbeing depression anxiety stress level iranian patients ms covid19 pandemic stagemethods one hundred sixtyfive patients enrolled asked cases fill valid reliable persian version depression anxiety stress scale dass21 perceived social support fear relapse scale questionnairesresults one hundred sixtyfive patients enrolled female male ratio f m 46 mean age mean duration disease 35386 715 years respectively mean scores social support dass questionnaires 631168 164134 514173 respectively significant negative correlation social support scores also significant positive correlations components dass linear regression analysis considering dependent variable age sex marital status duration disease edss dependent variables showed sex independent predictor scoreconclusion psychological wellbeing well fear relapse considered patients ms covid19 pandemic stagepmid33860396 doi101007 s10072021052538,0.0
b cells multiple sclerosis targeted depletion immune reconstitution therapies nat rev neurol 2021 jun 1 doi 101038 s41582021004985 online ahead printabstractincreasing evidence indicates involvement b cells pathogenesis multiple sclerosis ms precise roles unclear review provide overview development physiological functions b cells main mechanisms b cells thought contribute cns autoimmunity ms abnormalities b cell function include proinflammatory cytokine production defective b cell regulatory function formation tertiary lymphoidlike structures cns likely source abnormal immunoglobulin production detectable cerebrospinal fluid also consider hypothesis epsteinbarr virus ebv involved b cell overactivation leads inflammatory injury cns ms also review immunological effects focus effects b cell subsets several successful therapeutic approaches ms including agents selectively deplete b cells rituximab ocrelizumab ofatumumab agents less specifically deplete lymphocytes alemtuzumab cladribine autologous haematopoietic stem cell transplantation immune system unselectively ablated reconstituted consider insights effects b cell populations provide potential understanding targeting b cells mspmid34075251 doi101038 s41582021004985,0.0
controlled trial two mindbody interventions grief widows widowers j consult clin psychol 2021 jul 89 7 640654 doi 101037 ccp0000653abstractobjective following bereavement yearning grief rumination repetitive cognitive processes can lead disordered grief mindfulness training mt shown reduce maladaptive repetitive thought current quasirandomized controlled trial examined feasibility acceptability preliminary efficacy mt bereavementrelated grief method ninetyfive widow er s mage 675 79 women 98 white 6 months 4 years postloss assigned 6week mt intervention progressive muscle relaxation pmr intervention waitlist condition outcome measures grief severity revised inventory complicated grief yearning yearning situations loss rumination utrecht grief rumination scale decentering experiences questionnairedecentering assessed baseline weeks 2 4 intervention postintervention 1month postintervention growth curve analysis examined group differences rates improvement outcomes followup associations improvement grief severity results mt pmr groups showed significant rates decline grief severity yearning though pmr group showed greater rate decline grief severity waitlist groups showed significant rates decline grief rumination pmr waitlist groups showed significant rates increase decentering compared mt group conclusions results support feasibility acceptability mt pmr widow er s well preliminary efficacy pmr improving grief severity widow er s compared waitlist control condition replication pmr standalone intervention nondisordered grief component treatment disordered grief psycinfo database record c 2021 apa rights reserved pmid34383536 doi101037 ccp0000653,0.0
fingolimod therapy multiple sclerosis leads enrichment subpopulation aged nk cells neurotherapeutics 2021 jul 9 doi 101007 s13311021010787 online ahead printabstractfingolimod approved oral treatment relapsingremitting multiple sclerosis rrms modulates agonistically sphingosin1phosphate receptor s1pr inhibiting thereby egress lymphocytes lymph nodes interventional prospective clinical phase iv trial longitudinally investigated impact fingolimod frequencies nk cell subpopulations flow cytometry 17 rrms patients baseline 1 3 6 12 months treatment initiation clinical outcome assessed expanded disability status scale edss annualized relapse rates arr study period median edss remained stable month 3 month 12 arr decreased compared arr 24 months prior treatment treatment paralleled increased frequency circulating nk cells due primarily increase cd56dimcd94low mature nk cells cd56bright fraction cd127+ innate lymphoid cells ilcs decreased time unsupervised clustering algorithm revealed particular fraction nk cells defined expression cd56dimcd16++kir+ nkg2acd94ccr7+ cx3cr1+ nkg2cnkg2d+nkp46dnam1++cd127+ increased treatment specific phenotype might reflect status aged fully differentiated less functional nk cells study confirms fingolimod treatment affects nk cells ilc addition study suggests treatment leads enrichment specific nk cell subset characterized aged phenotype might limit antimicrobial antitumour nk cell activity fingolimodtreated patientspmid34244929 doi101007 s13311021010787,0.0
brain structural alterations mog antibody diseases comparative study aqp4 seropositive nmosd ms j neurol neurosurg psychiatry 2021 mar 9jnnp2020324826 doi 101136 jnnp2020324826 online ahead printabstractbackground brain structural alterations clinical significance myelin oligodendrocyte glycoprotein antibody disease mogad determinedmethods recruited 35 mogad 38 aquaporin 4 antibody positive neuromyelitis optica spectrum diseases aqp4+ nmosd 37 multiple sclerosis ms 60 healthy controls hc underwent multimodal brain mri two centres brain lesions volumes whole brain parenchyma cortical subcortical grey matter gm brainstem cerebellum cerebral white matter wm diffusion measures fractional anisotropy fa mean diffusivity md compared among groups associations mri measurements clinical variables assessed partial correlations logistic regression performed differentiate mogad aqp4+ nmosd msresults mogad 19 54 patients lesions mri cortical juxtacortical 68 common location mogad ms showed lower cortical subcortical gm volumes hc aqp4+ nmosd demonstrated decreased cortical gm volume ms demonstrated lower cerebellar volume lower fa increased md mogad hc subcortical gm volume negatively correlated expanded disability status scale mogad r051 p0004 combination mri clinical measures achieve accuracy 85 93 classification mogad versus aqp4+ nmosd mogad versus ms respectivelyconclusion mogad demonstrated cortical subcortical atrophy without severe wm rarefaction subcortical gm volume correlated clinical disability combination mri clinical measures separate mogad aqp4+ nmosd mspmid33687975 doi101136 jnnp2020324826,1.0
early age onset predicts severity visual impairment patients neuromyelitis optica spectrum disorder abstractbackgroundsevere residual visual loss srvl frequent neuromyelitis optica spectrum disorders nmosd identifying higherrisk patients onset important prevent disability accumulationobjectiveto determine predictors srvl large nmosd cohortmethodspatient characteristics last visual acuity va evaluation retrospectively collected va scored 0 better 20 40 1 20 4020 99 2 20 10020 200 3 worse 20 200 srvl defined combined score va worst + best eye 4 descriptive statistics used compare groups logistic regression evaluate predictors varesults106 patients mean age disease onset ao 358 165years included patients srvl earlier ao mean 267 vs 380years compared nonsrvl group p 0005 patients ao 21years likely srvl blind present binocular optic neuritis recurrent optic neuritis receive oral therapy firstline ao 21 adjusting race sex disease duration odds srvl 468 times higher patients 21 disease onset 95 ci 1531434 p 0007 conclusionearly ao predicts srvl nmosd independent disease duration highefficacy therapies considered firstline treatment group,0.0
polymorphism dna repair gene xdp increases risk systemic lupus erythematosus multiple sclerosis iranian population mult scler relat disord 2021 apr 28 52102985 doi 101016 jmsard2021102985 online ahead printabstractbackground xeroderma pigmentosum group d xpd essential component nucleotide excision repair ner pathway can play major role dna repair processes deficiency pathway suggested causative factor autoimmune diseases therefore current study aimed investigate relationship xpd lys751gln polymorphism rs13181 one common xdp polymorphisms risk two important autoimmune diseases namely systemic lupus erythematosus sle multiple sclerosis ms iranian populationmethods 165 sle patients 165 age gendermatched healthy controls 150 ms patients 150 age gendermatched healthy controls genotyped xpd rs13181 c polymorphism using polymerase chain reactionrestriction fragment length polymorphism pcrrflp methodresults results present study indicated c allele frequency p 0012 odds ratio 15 95 confidence interval 11207 cc genotype p 0007 odds ratio 246 95 confidence interval 1247 sle patient significantly higher control group furthermore significant differences ms patients normal subjects concerning genotype allele frequenciesconclusion findings suggested xpd rs13181 c polymorphism may crucial risk factor development sle ms iranian patientspmid33984652 doi101016 jmsard2021102985,0.0
inhibition cd38 supplementation nicotinamide riboside ameliorate lipopolysaccharideinduced microglial astrocytic neuroinflammation increasing nad j neurochem 2021 apr 19 doi 101111 jnc15367 online ahead printabstractneuroinflammation initiated activation brains innate immune system response inflammatory challenge insufficient control neuroinflammation leads enhanced prolonged pathology various neurological conditions including multiple sclerosis alzheimers disease nicotinamide adenine dinucleotide nad+ plays critical roles cellular energy metabolism calcium homeostasis previous study demonstrated deletion cd38 consumes nad+ suppressed cuprizoneinduced demyelination neuroinflammation glial activation however still unknown whether cd38 directly affects neuroinflammation regulating brain nad+ level study investigated effect cd38 deletion inhibition supplementation nad+ lipopolysaccharide lps induced neuroinflammation mice first intracerebroventricular injection lps significantly increased cd38 expression especially hippocampus deletion cd38 decreased lpsinduced inflammatory responses glial activation preadministration apigenin flavonoid cd38 inhibitory activity nicotinamide riboside nr nad+ precursor increased nad+ level significantly suppressed induction cytokines chemokines glial activation subsequent neurodegeneration lps administration cell culture lpsinduced inflammatory responses suppressed treatment primary astrocytes microglia apigenin nad+ nr 78c latter specific cd38 inhibitor finally compounds suppressed nfb signaling pathway microglia results suggest cd38mediated neuroinflammation linked nad+ consumption boosting nad+ cd38 inhibition nr supplementation directly suppress neuroinflammation brainpmid33871064 doi101111 jnc15367,1.0
lateralization bias autoimmune optic neuritis mult scler relat disord 2021 apr 28 52102980 doi 101016 jmsard2021102980 online ahead printabstractthe asymmetrical structure human brain reflected innate interhemispheric differences also lateralization neurological disease tested unilateral autoimmune optic neuritis aon manifests frequently left right eye clinical neuroimaging terms whether google searches aon symptoms reflect bias employed retrospective analysis patient cohort 2009 2019 552 unilateral aons 374 corresponding mri imaging data sets searchmetrics suite keywords tool applied analysis google searches aonsymptoms germany us uk last 12 months left eye aon manifestations frequent right aon manifestations 553 vs 447 p 0015 19 times likely associated pathological mri finding affected optic nerve p 0013 keywords describing aontypical ocular symptoms frequently associated google searches left comparison right eye p 0001 autoimmune optic neuritis frequently affects left right eye people search internet often leftsided aon symptoms although reporting bias due increased perception left eye symptoms one possible explanation mri evidence frequent optic nerve affection left comparison right side suggests leftward lateralization bias similar one previously shown cerebral neuroinflammatory lesionspmid33984650 doi101016 jmsard2021102980,0.0
drb1environment interactions multiple sclerosis etiology results two swedish casecontrol studies j neurol neurosurg psychiatry 2021 mar 9jnnp2020325676 doi 101136 jnnp2020325676 online ahead printabstractobjective aimed investigate influence environmental risk factors multiple sclerosis ms different genetic contexts study interactions environmental factors human leucocyte antigen hla genes differ magnitude according heterozygocity homozygocity hladrb11501methods using populationbased casecontrol studies 6985 cases 6569 controls subjects different genotypes smoking ebna1 status adolescent body mass status compared regarding ms risk calculating 95 ci employing logistic regression interaction different genotypes environmental factor evaluated additive scaleresults effect drb11501 allele ms risk additive logodds scale additional allele interaction drb11501 assessed environmental factor similar magnitude regardless number drb11501 alleles although ors affected environmental factors present drb11501 carriers without protective a0201 allele threeway interaction occurred rendered high ors especially among drb11501 homozygotes 200 95 ci 131 305 among smokers 219 95 ci 150 318 among elevated ebna1 antibody levels 443 95 ci 135 145 among reported adolescent overweight obesity conclusions strikingly increased ms risk among drb1501 homozygotes exposed environmental factors argument favour factors acting immunerelated mechanisms data reinforce importance preventive measures particular genetic susceptibility mspmid33687974 doi101136 jnnp2020325676,0.0
assessment macular function multifocal electroretinogram patients multiple sclerosis treated fingolimod adv ther 2021 jun 9 doi 101007 s12325021017284 online ahead printabstractintroduction study aimed evaluate whether treatment fingolimod fty may induce functional changes macular preganglionic retinal elements patients affected relapsingremitting multiple sclerosis rrms without optic neuritis methods casecontrol observational retrospective study assessed multifocal electroretinogram mferg responses 35 healthy controls mean age 4358 576 years 41 patients rrms without mean age 4064 483 years msnofty group 21 patients rrms without mean age 4238 1234 years treated fingolimod gilenya novartis europharm 05 mg day msfty group mferg n1 p1 implicit times n1p1 response amplitude densities rads measured concentric rings r increasing foveal eccentricity 05 r1 510 r2 1015 r3 1520 r4 2025 r5 considered r1 r2 central macular areas r3 r4 r5 eccentric retinal areas msfty group mferg recordings performed 6 12 months mean 72 15 months start ftyresults msfty group mean values mferg n1 p1 rads detected central macular areas r1 r2 eccentric retinal areas r3 r4 r5 significantly different p 001 respect control msnofty groupsconclusions mferg results suggest chronic use fty induce dysfunction preganglionic retinal elements located 025 central retina since fty cause retinal functional abnormality suggest fty treatment produce toxic effect preganglionic retinal elements even absence macular oedemapmid34109558 doi101007 s12325021017284,0.0
serum vasohibin1 levels potential marker dermal pulmonary fibrosis systemic sclerosis exp dermatol 2021 mar 8 doi 101111 exd14321 online ahead printabstractvasohibin1 vash1 potent antiangiogenic factor mainly produced endothelial cells addition vash1 prevents tgfdependent activation renal fibroblasts since systemic sclerosis ssc autoimmune disease characterized vasculopathy fibrosis multiple organs vash1 may involved development disease study investigated potential role vash1 ssc evaluating clinical correlation serum vash1 levels expression vash1 sscinvolved skin serum vash1 levels higher ssc patients especially diffuse cutaneous involvement healthy controls positively correlated skin score furthermore ssc patients interstitial lung disease significantly elevated levels serum vash1 compared without importantly serum vash1 levels correlated inversely percentage predicted vital capacity percentage predicted diffusion lung capacity carbon monoxide positively serum kl6 levels serum surfactant proteind levels sscinvolved skin vash1 mrna remarkably upregulated compared healthy control skin major source vash1 clear fli1 deficiency predisposing factor inducing ssclike endothelial properties affect vash1 expression human dermal microvascular endothelial cells collectively results suggest vash1 upregulation skin sera linked dermal pulmonary fibrotic changes ssc contribution vash1 ssc vasculopathy seems limitedpmid33682189 doi101111 exd14321,0.0
comprehensive assessment patient experience diseaserelated awareness multiple sclerosis questionnairebased nationwide survey turkey mult scler relat disord 2021 may 7 52103005 doi 101016 jmsard2021103005 online ahead printabstractbackground comprehensive assessment multiple sclerosis ms patients terms patient profile clinical diseaserelated factors great epidemiological value study aimed evaluate patient experience diseaserelated awareness ms patients nationwide survey turkey methods total 1379 ms patients participated crosssectional questionnaire survey conducted november 2018 december 2018 online questionnaire form included items sociodemographic diseaserelated firstadmission treatment follow characteristics well disability statusresults patients diagnosed median 280 years age average time admission diagnosis time diagnosis treatment 12 years 25 months respectively neurology 454 ophthalmology 233 common clinics first admission numbnessweakness lower upper extremities 376 double visionvisual problems 306 common symptoms initial admission treatment initiated diagnosis 1213 880 patients 166 120 patients treatmentnave treatment discontinuation treatment switch use alternative treatment methods reported 313 493 228 patients respectively ophthalmology admissions double vision visual problems associated shortest time presentation diagnosis compared neurosurgery internal medicine admissions median 10 vs 30 40 months p0001 neurology admissions numbnessweakness extremities associated prompt median 03 vs 05 months p0032 frequent onset treatment diagnosis 645 vs 22 152 p0001 time presentation diagnosis longer patients aged 50 years median 60 months vs 20 months p0001 patients using alternative medicine median 30 months vs 1 month p0001 patients admitted nonmscenter median 30 months vs 20 months p0002 median minmax age diagnosis significantly lower patients vs without treatment discontinuation reason 260 1056 vs 290 360 years p0001 treatment switching 270 593 vs 300 360 years p0001 conclusions conclusion findings revealed higher likelihood earlier diagnosis earlier treatment patients admitted mscenter presenting ocular problems sensorymotor deficits respectively findings also emphasize association older patient age higher likelihood diagnostic delay increased likelihood treatment discontinuation reason treatment switching case older patient age younger age diagnosis diagnostic delay regard findings highlight need improved awareness among patients well clinicians initial manifestations ms enable admission referral mscenter prevent delay diagnosis particularly onset symptoms ocular sensorymotor characteristicspmid34000682 doi101016 jmsard2021103005,0.0
challenges switching towards anticd20 monoclonal antibodies rrms monocentric study mult scler relat disord 2021 apr 28 52102981 doi 101016 jmsard2021102981 online ahead printabstractbackground anticd20 monoclonal antibodies mab demonstrated drastic efficacy treatment active relapsingremitting multiple sclerosis rrms study investigates management initiation another disease modifying therapy dmt objective study assess frequency risk factors relapses washout period wp cessation last dmt initiation anticd20 mab rrmsmethods nonnaive rrms patients initiated treatment rituximab ocrelizumab 2016 2019 included retrospective monocentric study univariate multivariate analysis conducted evaluate risk factors relapses wpresults 73 patients mean age 353 years standard deviation sd 87 years included mean number 31 sd 13 previous dmts dmt frequently received switch fingolimod fg 31 patients 425 20 patients 274 experienced relapses wp risk factors previous treatment fg p 0001 wp duration p 0032 among patients switching fg probability experiencing relapse 35 1 month washoutconclusion study suggests shorten wp duration switching towards anticd20 mab especially fg avoid relapsespmid34004434 doi101016 jmsard2021102981,0.0
paucimyces polynucleatus gen nov sp nov novel polycentric genus anaerobic gut fungi faeces wild blackbuck antelope int j syst evol microbiol 2021 jun 71 6 doi 101099 ijsem0004832abstractthe anaerobic gut fungi agf phylum neocallimastigomycota reside alimentary tracts herbivores multiple novel yetuncultured agf taxa recently identified cultureindependent diversity surveys report isolation characterization first representative rh5 lineage faecal samples wild blackbuck indian antelope antilope cervicapra sutton county texas usa isolates displayed medium sized 24 mm compact circular colonies agar roll tubes thin loose biofilmlike growth liquid medium microscopic examination revealed monoflagellated zoospores polycentric thalli highly branched nucleated filamentous rhizomycelium growth pattern encountered minority described agf genera far obtained isolates characterized formation spherical vesicles hyphal tips multiple sporangia formed either directly spherical vesicles end sporangiophores phylogenetic analysis using d1 d2 regions large ribosomal subunit d1 d2 lsu ribosomal internal transcribed spacer 1 its1 revealed sequence similarities 935 813 respectively closest cultured relatives orpinomyces joyonii strain d3a d1 d2 lsu joblinomyces apicalis strain gfh681 its1 substrate utilization experiments using type strain bb3t demonstrated growth capabilities wide range mono oligo polysaccharides including glucose xylose mannose fructose cellobiose sucrose maltose trehalose lactose cellulose xylan starch raffinose propose accommodating novel isolates new genus species name paucimyces polynucleatus gen nov sp nov proposedpmid34161217 doi101099 ijsem0004832,0.0
populationbased headtohead comparison clinical characteristics epidemiology aqp4 antibodypositive nmosd two european countries mult scler relat disord 2021 mar 3 51102879 doi 101016 jmsard2021102879 online ahead printabstractbackground populationbased clinical studies neuromyelitis optica spectrum disorder nmosd epidemiological clinical comparisons white ethnicities missing large populationbased international cohort extensively characterized aquaporin4 antibody seropositive aqp4ab+ nmosd also compared clinical radiological epidemiological features two european populations residing different areasmethods selfreported danish hungarian ethnicities compared populationbased clinical features disability outcomes death 134 aqp4ab+ nmosd cases fulfilling 2015 international panel nmo diagnosis ipnd criteria precise comparison epidemiology conducted populationbased headtohead comparative study agestandardized prevalence january 1 2014 incidence 20072013 aqp4ab+ nmo nmosd among adults 16 years denmark 46 million hungary 64 million applying 2015 ipnd nmosd criteria 2006 wingerchuk nmo results danes likely present transverse myelitis affected spinal cord damage longterm disability hungarians presented often optic neuritis although visual outcome similar groups differences observed sex disease course relapse rate autoimmune comorbidity mortality brain mri treatment strategies agestandardized prevalence estimates aqp4ab+ nmosd 2015 ipnd criteria denmark vs hungary 066 vs 143 100 000 incidence rates 004 vs 011 100 000 personyears similar differences found based 2006 nmo criteriaconclusions headtohead comparative study indicates different disease characteristics epidemiology among white populations europe substantiates need populationbased genetic environmental studies nmosdpmid33714126 doi101016 jmsard2021102879,0.0
analysis inflammasomes cyp27b1 genes cuprizone demyelinated c57bl 6 mice evaluation th1 th2 patterns oral adminstration lactobacillus casei strain t2 ibrcm10783 microb pathog 2021 apr 27104931 doi 101016 jmicpath2021104931 online ahead printabstractmultiple sclerosis characterized destruction myelin cns various factors including genetics epigenetics environmental factors involved development disease evidence changes gut microbiome profile associated immunerelated diseases ms probiotics can alter composition gut microbiota mucosal surfaces differentiating naive t cells th1 th2 th17 treg cells female c57bl 6 mice divided 6 groups n 7 normal group cuprizone group gavage cuprizone 4 weeks probiotic group gavage probiotic 4 weeks treatment1 group probiotic 4 weeks cuprizone 4 weeks treatment2 group cuprizone 4 weeks probiotic 4 weeks treatment3 group cuprizone 4 weeks probiotic 4 weeks vitamin d3 expression nlrp1 nlrp3 aim2 cyp27b1 genes evaluated using realtime pcr serum levels ifn il4 also measured elisathe results showed significant decrease expression inflammasome cyp27b1 genes probiotictreated groups compared cuprizone group also comparison probiotictreated groups cuprizone group showed significant decrease amount ifn il4 due reduced expression inflammasome genes well decrease ifn levels inflammatory cytokine appears l casei may effective healing process demyelinated micepmid33930419 doi101016 jmicpath2021104931,1.0
prioritizing progressive ms rehabilitation research call international progressive ms alliance mult scler 2021 mar 151352458521999970 doi 101177 1352458521999970 online ahead printabstractbackground people multiple sclerosis ms experience myriad symptoms negatively affect quality life despite significant progress rehabilitation strategies people living relapsingremitting ms rrms development similar strategies people progressive ms received little attentionobjective highlight key symptoms importance people progressive ms stimulate design implementation highquality studies focused symptom management rehabilitationmethods group international research experts representatives industry people affected progressive ms convened international progressive ms alliance devise research priorities addressing symptoms progressive msresults based information ms community outline rationale highlighting four symptoms particular interest fatigue mobility upper extremity impairment pain cognitive impairment factors depression resilience comorbidities psychosocial support described affect treatment efficacyconclusions coordinated call actionto research community prioritize investigation effective symptom management strategies funders support themis important step addressing gaps rehabilitation research people affected progressive mspmid33720795 doi101177 1352458521999970,0.0
ms disability progression latin america africa asia middle east systematic review mult scler relat disord 2021 mar 9 51102885 doi 101016 jmsard2021102885 online ahead printabstractbackground evidence increased prevalence disease burden multiple sclerosis ms parts world risk considered low latin america la subsaharan africa asia middle eastnorth africa mena despite growing number clinical reports phenotype course ms regions remains understudied compared europe north america aimed investigate ms phenotypes longterm clinical outcomes across regionsmethod boolean search medical literature conducted january 1980 april 30 2020 pubmed scopus global health cochrane databases used identify relevant citations articles collated managed covidence software independently appraised articles meeting study criteria quality using critical appraisal skills program casp specialist unit review evidence sure systemresults total 1 639 studies imported screening removing 545 duplicates two authors assessed 1 094 abstracts selected 515 fulltext screening 72 articles met study criteria including 19 studies la 4 subsaharan africa 24 asia 25 mena overall sex ratio 251 female male disability assessed using expanded disability status scale edss longitudinal disability progression time standard endpoints compared region relevant western reports patients ms living mena region appear reach disability milestones faster western world although finding uniform south asia shows distinct disability features compared east asia closely resembling west disease morbidity east asia appears benign west careful exclusion neuromyelitis optica spectrum disorder cases populations la tend similar ms features western world exceptions exist including african descendants reach disability milestones earlier using studies appropriate survival analysis mean time edss 60 1697 years heterogeneity index 2459conclusion clinical phenotypes disability progression ms la africa asia mena region similarities western ms regions subpopulations evidence aggressive course possibly due combination genetic environmental factors populationbased longitudinal data needed particularly subsaharan africapmid33773273 doi101016 jmsard2021102885,0.0
use cannabis patients multiple sclerosis argentina mult scler relat disord 2021 apr 6 51102932 doi 101016 jmsard2021102932 online ahead printabstractbackground use cannabis treat symptoms neurological diseases including multiple sclerosis ms increased worldwide aimed assess use cannabis patients ms pwms argentina reasons patients perceptions management ms symptoms additionally assessed association sociodemographic clinical aspectsmethods crosssectional online survey included 281 pwms argentina conducted screening instruments demographics clinical data healthrelated qol ms impact scale29 fatigue severity scale hospital anxiety depression scale sleep disorders physical disability selfadministrated expanded disability status scale medical recreational cannabis use evaluated logistic regression model carried outresults current users cannabis used within past year reported 342 former users tried cannabis used within past year 227 daily cannabis use reported 313 current + former users studied cohort 419 started use ms diagnosis 543 never discussed cannabis use neurologist recreational use reported 475 younger age 30 years pwms 239 p 003 presence chronic pain 242 p 0002 current alcohol intake 333 p 0001 predictors current cannabis use multivariate modelconclusion high prevalence use cannabis pwms argentina observed demographic symptoms lifestyle factors predict cannabis use identifying presence severity conditions contribute better ms management treatmentpmid33848817 doi101016 jmsard2021102932,0.0
multiple sclerosis ann intern med 2021 jun 1 doi 107326 aitc202106150 online ahead printabstractmany groundbreaking advances occurred field multiple sclerosis since series last reviewed disorder 2014 us food drug administration approved 7 new medications relapsingremitting multiple sclerosis approved first medication primary progressive multiple sclerosis mcdonald criteria diagnosing multiple sclerosis updated 2017 new blood tests can now differentiate patients multiple sclerosis neuromyelitis optica spectrum disorder 3 new medications approved specifically latter disorder also new medications treating symptoms multiple sclerosis introducedpmid34097429 doi107326 aitc202106150,1.0
targeting sphingosine1phosphate signaling immunemediated diseases beyond multiple sclerosis drugs 2021 may 13 doi 101007 s40265021015288 online ahead printabstractsphingosine1phosphate s1p bioactive lipid metabolite exerts actions engaging 5 gproteincoupled receptors s1pr1s1pr5 s1p receptors involved several cellular physiological events including lymphocyte hematopoietic cell trafficking s1p gradient low tissues high blood maintained synthetic degradative enzymes regulates lymphocyte trafficking lymphocytes live long critical adaptive immunity recirculate thousands times s1ps1pr pathway involved pathogenesis immunemediated diseases s1pr1 modulators lead receptor internalization subsequent ubiquitination proteasome degradation renders lymphocytes incapable following s1p gradient prevents access inflammation sites drugs might also block lymphocyte egress lymph nodes inhibiting transendothelial migration targeting s1prs therapeutic strategy first employed multiple sclerosis ms four s1p modulators fingolimod siponimod ozanimod ponesimod currently approved treatment new s1pr modulators clinical development ms uses evaluated treat immunemediated diseases including inflammatory bowel disease ibd rheumatoid arthritis ra systemic lupus erythematosus sle psoriasis clinical trial patients covid19 treated ozanimod ongoing ozanimod etrasimod shown promising results ibd phase 2 clinical trials ponesimod shown improvement 77 patients psoriasis cenerimod amiselimod tested sle patients fingolimod etrasimod immh001 shown efficacy ra preclinical studies concerns relating s1pr modulators leukopenia anemia transaminase elevation macular edema teratogenicity pulmonary disorders infections cardiovascular events furthermore s1pr modulators exhibit different pharmacokinetics wellestablished firstdose event associated s1pr modulators can mitigated gradual uptitration conclusion s1p modulators represent novel promising therapeutic strategy immunemediated diseasespmid33983615 doi101007 s40265021015288,0.0
effects prolongedrelease fampridine multiple sclerosisrelated gait impairments crossover doubleblinded placebocontrolled study clin biomech bristol avon 2021 may 12 86105382 doi 101016 jclinbiomech2021105382 online ahead printabstractbackground people multiple sclerosis reduced walking speed impaired gait pattern prolonged releasefampridine potassium channel blocker improves nerve conduction patients multiple sclerosis leading walking benefits whether fampridine alters gait pattern unknownmethods crossover randomized controlled trial patients multiple sclerosis tested responder status 4week runin period patients considered responders improved 25ft walk test 10 improved perceived walking capacity responders randomized prolonged releasefampridine 10 mg bid placebo 6week period 2week washout period allocated treatment 6 weeks participants assessed conditions threedimensional gait analysis assessed kinematic kinetic mechanic energetic variables walking treadmill comfortable speed sixminute walk test 25ft walk test used assess walking speed middle shortdistances respectively patientreported outcome measures also used repeated measures ancovas applied assess treatment effectsfindings 39 included patients 24 responders 12 women expanded disability status scale425 45 age46 10 years maximal speed093 038 ms1 identified among prolonged releasefampridine reduced external mechanical work 0039 jkg1m1 p 002 improved knee flexion swing phase +53 p 002 differences found walking tests patientreported outcomes grouplevelinterpretation prolonged releasefampridine increases knee flexion swing phase lowers mechanical external work whether changes related clinically meaningful improvements walking capacity functional variables investigatedpmid34000628 doi101016 jclinbiomech2021105382,0.0
use antitnfalpha therapy crohn#39 s disease associated increased incidence multiple sclerosis mult scler relat disord 2021 apr 9 51102942 doi 101016 jmsard2021102942 online ahead printabstractobjective investigated antitumor necrosis factor antitnf drugs used treatment inflammatory bowel disease ibd alter incidence ms understand magnitude effectmethods retrospective cohort study data truven health market scan administrative claims database patients included study 18 years age presence ibd based least 2 claims international classification diseases icd9 10 diagnosis codes ibd diagnosis index date precede ms diagnosis index date inclusion study diagnosis multiple sclerosis ms defined least 2 claims disease icd 9 340 icd 10 codes g35 least one prescription claim drugs defined ms therapyresults patients ibd 132 times risk ms incidence compared healthy controls adjusted incidence rate ratio irr 132 95 ci 103 171 p 0312 patients ibd exposed antitnf therapies 43 increase incidence ms compared ibd without exposure adjusted incidence rate 143 95 ci 062 332 p 3989 among cd patients treated antitnf medications increase incidence ms compared cd patients exposed medications observed irr 262 95 ci 100 683 p 0049 statistically significant adjusting age gender patients cd using antitnf agents increase incidence ms adjusted irr 224 95 ci 085 594 p 1035 statistically significantconclusions use antitnf drugs cd associated statistically significant increase incidence ms effect lost controlled age genderpmid33933908 doi101016 jmsard2021102942,0.0
staufen1 human neurodegeneration ann neurol 2021 mar 21 doi 101002 ana26069 online ahead printabstractobjective mutant expansions dna cag 32 repeats atxn2 can rare cause parkinson disease amyotrophic lateral sclerosis als recently reported stress granule sg protein staufen1 stau1 overabundant neurodegenerative disorder sca2 patient cells animal models alstdp43 fibroblasts provided link sg formation autophagy aimed test stau1 overabundance role pathogenesis neurodegenerative diseasesmethods multiple neurodegenerative patientderived cell models animal models human postmortem als tissue evaluate stau1 function using biochemical immunohistological analysesresults demonstrate stau1 overabundance increased total phosphorylated mammalian target rapamycin mtor fibroblast cells als patients mutations tdp43 dementia patients psen1 mutations parkinsonism patient mapt mutation huntington disease hd mutations sca2 mutations increased stau1 levels mtor activity seen human als spinal cord tissues well animal models changes stau1 mtor protein levels posttranscriptional exogenous expression stau1 wildtype cells sufficient activate mtor downstream targets form sgs targeting stau1 rnai normalized mtor suggesting potential role therapy diseases associated stau1 overabundanceinterpretation stau1 overabundance neurodegeneration common phenomenon associated hyperactive mtor targeting stau1 asos mirna viral vectors may represent novel efficacious therapy neurodegenerative diseases characterized overabundant stau1 article protected copyright rights reservedpmid33745139 doi101002 ana26069,0.0
integrating patientreported outcomes quantitative timed tasks identify relapsing remitting multiple sclerosis patient subgroups latent profile analysis mult scler relat disord 2021 mar 18 51102912 doi 101016 jmsard2021102912 online ahead printabstractbackground multiple sclerosis ms patients experience wideranging symptoms varied severity approaches integrate patientreported outcomes objective quantitative measures will present opportunities advancing clinical profiling primary objective current study conduct exploratory data analysis using latent variable modeling empirically identify clusters relapsing remitting rr ms patients shared impairment patterns across three patientreported outcomes two timed task measuresmethods latent profile analyses impairment data 2 012 rrms patients identified distinct patient clusters using timed task measures upper lower limb performance patientreported outcomes measuring quality life depression symptom severity perceived global disability multinomial logistic regression models used characterize associations sociodemographic attributes assignment patient clustersresults 6 distinct clusters rrms patients differed symptom patterns sociodemographic attributes notable differences age sex disease duration least impaired classes representing 14 4 patients respectively patients impaired class much likely black american history smoking higher body mass index lower socioeconomic status least impaired class positive relationships age classification clusters increasing moderately severe impairment severe clustersconclusion present framework discerning phenotypic impairment clusters rrms results demonstrate opportunities advancing clinical profiling necessary optimizing personalized ms care models clinical researchpmid33773274 doi101016 jmsard2021102912,0.0
comparative responsiveness health utilities index rand12 multiple sclerosis abstractbackgroundoutcome measures need valid good testretest reliability responsiveness compared responsiveness rand12 health utilities indexmark iii hui3 persons multiple sclerosis ms methodsin spring 2018 2019 north american research committee multiple sclerosis narcoms registry participants completed hui3 rand12 reported disability patient determined disease steps pdds employment status fulltime parttime used changes pdds employment status anchors assessed responsiveness using effect size standardized response mean responsiveness index used relative efficiency re compare responsiveness healthrelated quality life hrqol scores adjusting sociodemographic factorsresultswe included 4769 participants analysis mean standard deviation sd age 609 101 years 3826 participants 802 women re highest hui3 changes disability status hui3 10 physical component score12 pcs12 080 mental component score12 mcs12 041 changes employment status hui3 10 pcs12 070 mcs12 017 conclusionthe hui3 responsive changes disability employment status pcs12 mcs12 given hui3s strong psychometric properties may preferred generic measure hrqol ms,0.0
emerging role fty720 sphingosine 1phosphate analog treatment ischemic stroke cellular molecular mechanisms brain behav 2021 may 10e02179 doi 101002 brb32179 online ahead printabstractfinding novel effective drugs treatment ischemic stroke warranted definitive treatment prevalent disease due relevance sphingosine 1phosphate s1p receptor several neurological diseases including ischemic stroke seems fingolimod fty720 agonist s1p receptor can useful therapeutic strategy patients fty720 first oral drug approved us food drug administration treatment multiple sclerosis three important mechanisms neuroprotective effects fty720 described first functional antagonistic mechanism associated lymphopenia reduced lymphocytic inflammation effect results downregulation degradation lymphocytes s1p receptors inhibits lymph node lymphocytes entering bloodstream second functional agonistic activity mediated direct effects via targeting s1p receptors membrane various cells including neurons microglia oligodendrocytes astrocytes endothelial cells blood vessels central nervous system cns third receptorindependent mechanisms displayed binding specific cellular proteins modulate intracellular signaling pathways affect epigenetic transcriptions therefore review mechanisms detail describe animal model clinical trial studies support three mechanisms neuroprotective action fty720 ischemic strokepmid33969931 doi101002 brb32179,1.0
differential diagnosis multiple sclerosis presse med 2021 oct 26104092 doi 101016 jlpm2021104092 online ahead printabstractbackground objectives despite immense progress imaging updates macdonald criteria diagnosis multiple sclerosis remains difficult must integrate history clinical presentation biological markers imaging multitude syndromes resembling multiple sclerosis clinically imaging goal review help clinicians orient various diagnoses organized review two categories inflammatory autoimmune diseases close can confused multiple sclerosis noninflammatory syndromes can present symptoms imaging mimicking multiple sclerosismethod review literature conclusion progress imaging biological sciences drastically changed approach management multiple sclerosis developments also shined light variety diseases previously unknown poorly known therefore greatly expanding differential diagnosis multiple sclerosis autoimmune many diseases underlying biological mechanisms different multiple sclerosis rendering ms therapies usually inefficient crucial approach diseases utmost thoroughness integrating history clinical exam evolving ancillary tests rsum contexte et objectifs malgr dimmenses progrs en imagerie et les mises jour successives des critres de macdonald le diagnostic de la sclrose en plaque demeure difficile il doit intgrer histoire de la maladie examen clinique marqueurs biologiques et imagerie de nombreux syndromes ressemblent la sclrose en plaque soit par leur prsentation clinique soit par leur caractristiques radiologiques lobjectif de cette revue de la littrature est dorienter les cliniciens parmi ces diffrents diagnostics que nous classons en deux catgories maladies autoimmunes ou inflammatoire pouvant tre confondues avec la sclrose en plaque et syndromes noninflammatoires pouvant se prsenter avec des symptmes imitant la sclrose en plaques mthode revue de la littratureconclusion les progrs de limagerie et des sciences biologiques ont fondamentalement chang lapproche clinique et thrapeutique de la sclrose en plaques ces avances ont aussi mis en lumire une grande varit de maladies auparavant peu connues le diagnostic diffrentiel de la sclrose en plaque sen est trouv toff bien quautoimmuns par nature nombre de ces syndromes obissent des mcanismes physiopathologiques diffrents de la sclrose en plaque leur approche thrapeutique est donc radicalement diffrente il est crucial dapprocher ces pathologies avec rigueur en intgrant histoire de la maladie examen clinique et examens complmentairespmid34715293 doi101016 jlpm2021104092,0.0
sleep disturbance memory dysfunction early multiple sclerosis ann clin transl neurol 2021 may 5 doi 101002 acn351262 online ahead printabstractobjective sleepdependent memory processing occurs animals including humans disturbed sleep negatively affects memory sleep disturbance memory dysfunction common multiple sclerosis ms little known contributions sleep disturbance memory ms investigated whether subjective sleep disturbance linked worse memory early ms independently potential confoundersmethods persons early ms n 185 50 years diagnosed demographically matched healthy controls n 50 completed four memory tests derive memory composite four speeded tests derive cognitive efficiency composite zscores calculated relative healthy controls sleep disturbance defined insomnia severity index score 10 ancovas examined differences memory cognitive efficiency patients without sleep disturbance controlling potential confounds eg mood fatigue disability t2 lesion volume gray matter volume comparisons made healthy controlsresults seventyfour 40 patients reported sleep disturbance controlling covariates patients sleep disturbance worse memory z 0617 95 ci 0886 0348 patients without disturbance z 0171 0425 0082 p 003 cognitive efficiency differ groups relative healthy controls memory worse among patients sleep disturbance among patients without sleep disturbanceinterpretation sleep disturbance contributes ms memory dysfunction may help explain differential risk memory dysfunction persons ms especially since sleep disturbance common ms potential mechanisms linking sleep disturbance memory discussed well recommendations mechanistic interventional researchpmid33951348 doi101002 acn351262,0.0
community qigong people multiple sclerosis pragmatic feasibility study j altern complement med 2021 mar 26 doi 101089 acm20200481 online ahead printabstractobjectives qigong traditional chinese mindbody exercise shown improve balance gait several neurological conditions however communitydelivered qigong never assessed people multiple sclerosis ms authors assessed feasibility community qigong classes people ms explored outcomes balance gait quality life qol design twenty adults ms randomly assigned 10 weeks community qigong classes waitlist control settings location portland oregon subjects people ms intervention community qigong classes outcome measures feasibility criteria included recruitment retention adherence ability participate qigong movements secondary outcome measures included physical tests mobility gait balance participantreported mobility depression anxiety fatigue qol results recruitment eligible interested people ms feasible retention trial 60 completers attended mean 7 10 classes completers participated minor modifications qigong movements exploratory withingroup analyses showed trends toward improved mental health qol reduced fatigue depression several participants spontaneously reported improved energy flexibility sleep mobility conclusions community qigong may feasible form exercise people ms improve retention capture potential effects qigong physical function quality life future studies might consider pragmatic trials tiered level classes simpler forms qigong refined inclusion criteria ctr# nct04585659 pmid33769837 doi101089 acm20200481,0.0
update brain mri diagnosis followup ms patients presse med 2021 may 11104067 doi 101016 jlpm2021104067 online ahead printabstractover past decades mri become major tool diagnosis followup patients multiple sclerosis ms especially monitoring effectiveness therapy recent international recommendations issued standardization neurological radiological clinical practices converge many points setting recommendations made observatoire franais de la sclrose en plaques french ms registry can distinguished interdisciplinary complementarity longevity size positions direct connection clinic hence suspicions gadolinium deposition brain multiple warning american european health authorities national consultation took place resulted limitation useful injections precautionary principle prevailing patient receives limited quantity contrast product even clinically harmful manifestation detected date result round table bringing together neurologists neuroradiologists specialized centers published form recommendation early 2020 interest project also lies constant improvement management patients ms possibility developing advanced techniques assist clinician aim review explain neurologist interest following imaging protocol clinical practice possibilities opens uppmid33989722 doi101016 jlpm2021104067,0.0
retinal layer thinning predicts treatment failure relapsing multiple sclerosis eur j neurol 2021 mar 18 doi 101111 ene14829 online ahead printabstractbackground peripapillary retinal nerve fibre layer prnfl macular ganglion cell plus inner plexiform layer gcipl thinning markers neuroaxonal degeneration multiple sclerosis ms reduced diseasemodifying treatment dmt aimed investigate potential prnfl gcipl thinning prediction dmt failure relapsing ms rms methods 4year prospective observational study 113 rms patients prnfl gcipl measured dmt initiation 12 m12 24 months m24 treatment failure defined 6monthconfirmed edss progression symbol digit modalities test sdmt worsening optimal cutoff values predicting treatment failure determined receiveroperatingcharacteristic roc analyses hazard ratios hr multivariable cox regression adjusting age sex disease duration edss sdmt dmt classresults thinning gcipl 05m year m24 showed superior value treatment failure prediction hr 45 95 confidence interval ci 18 76 p0001 specificity 91 sensitivity 81 followed gcipl 05m m12 39 95 ci 14 69 p0001 specificity 85 sensitivity 78 prnfl 2m year m24 37 95 ci 11 65 p0023 specificity 84 sensitivity 69 prnfl m12 predictiveconclusions gcipl lesser degree prnfl thinning predicts disability progression dmt initiation may useful accessible biomarker treatment failure rmspmid33735479 doi101111 ene14829,0.0
atypical inflammatory demyelinating syndrome central peripheral nerve involvement mult scler relat disord 2021 mar 26 51102926 doi 101016 jmsard2021102926 online ahead printabstractwe report patient peripheral demyelination form chronic inflammatory demyelinating polyneuropathy cidp central demyelination following relapsingremitting disease course patient developed bilateral sequential optic neuritis predating diagnosis cipd developed profound brainstem syndrome ataxia dysarthria complex eye movement disorder visual disturbance urinary incontinence interval imaging fulfilled mcdonald criteria multiple sclerosis ms right parietooccipital tumefactive lesion showing contrast enhancement new lesions right temporal white matter midbrain tegmentum oligoclonal bands ocbs matched serum antibodies aquaporin4 aqp4 myelin oligodendrocyte glycoprotein mog negative genetic sequence analysis deletion duplication testing revealed variants uncertain significance compound heterozygosity point mutations two genes dync1h1 sh3tc2 associated charcotmarietooth cmt disease though patient negative known cmt mutations patient responded poorly steroids regular intravenous immunoglobulin ivig clinically improved following aggressive immunomodulatory therapy pulsed steroids plasmapheresis followed rituximab combined central peripheral demyelination ccpd rare autoimmune mechanisms postulated pathogenesis whether overlap central pe ripheral demyelination coincidental caused shared epitope peripheral central nervous systems still remains elucidated clear therapeutic consensus treatment central peripheral demyelination though immunomodulating treatment strategies may minimise disability improve prognosispmid34049139 doi101016 jmsard2021102926,1.0
short long term effects nabiximols balance walking assessed 3dgait analysis people multiple sclerosis spasticity mult scler relat disord 2021 jan 30 51102805 doi 101016 jmsard2021102805 online ahead printabstractbackground spasticity people multiple sclerosis pwms one disabling symptoms walking ability balance among systemic antispastic drugs nabiximols showed good tolerability safety profile relevant efficacy studies assessed longterm effects drug clinical scales instrumental tools study investigated shortterm effects aim study quantitatively evaluate immediate effects nabiximols walking balance maintenance 4 weeks pwms spasticitymethods pwms enrolled randomized 2 treatment groups sativex sg control cg group patients assessed t0 first sativex puff t1 45 minutes t2 4 weeks treatment using clinical scales 3dgait analysis patients treated sativex divided 5 subgroups according numeric rating scale spasticity nrss berg balance score bbs response nrss responder 1 non 2 bbs responders 3 non 4 nrssbbs responders 5 results 32 pwms 22 sg 10 cg recruited significant improvements found t0 t1 sg compared cg clinical kinematic parameters larger significant differences found nrss bbs responders groups versus cg eventually significant differences found comparing results t1 t2 suggesting persistence improvements emerged t1conclusion results quantitatively demonstrated short time effect nabiximols balance walking pwms mantained 4 weeks patients identified responder combination nrss bbs showed best efficacy findings may suggest early select real responders order improve adherence costeffectiveness therapypmid33862313 doi101016 jmsard2021102805,0.0
secondary progressive multiple sclerosis systematic review costs health state utilities curr med res opin 2021 mar 181 doi 101080 0300799520211904860 online ahead printabstractobjective identify evidence literature presenting economic humanistic based health state utility values hsuvs burden multiple sclerosis ms report incremental burden secondary progressive ms spms compared relapsingremitting ms rrms methods electronic databases embase medline medline inprocess cochrane library relevant repositories systematically searched date inception november 2019 evidence economic burden ms hsuvs patients ms data extracted studies investigating cost data hsuvs patients spms compared rrmsresults total 25 studies identified reported data economic hsuv burden spms versus rrms 18 studies reported cost data nine presented hsuvs overall costs associated spms consistently higher rrms major cost drivers appeared shift following transition rrms spms higher direct medical costs associated rrms spms opposite true direct nonmedical costs indirect costs studies presenting hsuvs specifically patients spms disease burden greater indicated lower hsuv scores negative regression coefficient vs rrms patients spms rrms fatigue psychological stress including depression identified key drivers reduced healthrelated quality life hrqol conclusions findings indicate spms associated higher costs substantial hrqol decrements rrms results highlight substantial unmet need effective treatments can slow disease progression patients spms turn reduce rate hrqol deterioration increasing healthcare costspmid33733976 doi101080 0300799520211904860,0.0
ozanimod treatment relapsing forms multiple sclerosis neurodegener dis manag 2021 may 20 doi 102217 nmt20210005 online ahead printabstractmultiple sclerosis ms inflammatory disease causes chronic neurological disability young adults modulation sphingosine 1phosphate s1p receptors group receptors among things regulate egression lymphocytes lymph nodes proven effective treating relapsing ms fingolimod first oral s1p receptor modulator demonstrated potent efficacy tolerability can cause undesirable side effects due interaction wide range s1p receptor subtypes review will focus ozanimod selective s1p receptor modulator recently received approval relapsing ms summarize ozanimods mechanism action efficacy safety clinical trials demonstrate utility another treatment option relapsing mspmid34011158 doi102217 nmt20210005,0.0
neutrophillymphocyte ratio marker disability activity multiple sclerosis mult scler relat disord 2021 mar 28 51102921 doi 101016 jmsard2021102921 online ahead printabstractbackground limited data regarding association neutrophillymphocyte ratio nlr inflammatory marker multiple sclerosis ms disability activityobjective aim present study evaluate validity nlr inflammatory marker ms disability activitymethods casecontrol study including 140 ms patients 140 age sex body mass index matched healthy controls performed participants subjected detailed history taking complete general neurological examination laboratory radiological investigations assessment disease disability performed using expanded disability status scaleresults nlr levels significantly higher ms patients compared controls patients relapse compared remission logistic regression analyses showed nlr significantly associated disease disability odds ratio 2568 confidence interval ci 1377 4788 p 0003 activity 3603 ci 2086 6226 p 002 cutoff value nlr predict ms disability activity 312conclusion nlr significantly increased ms patients compared controls significant association nlr ms disability activity suggest utilized simple rapid inexpensive inflammatory markerpmid33839481 doi101016 jmsard2021102921,0.0
oxysterols multiple sclerosis physiopathology evolutive biomarkers therapeutic strategy j steroid biochem mol biol 2021 mar 5105870 doi 101016 jjsbmb2021105870 online ahead printabstractmultiple sclerosis autoimmune disease affects central nervous system dysfunction immune system leads lesions cause motor sensory cognitive visual sphincter disturbances long term disorders can progress towards irreversible handicap diagnosis takes time specific criteria diagnose multiple sclerosis realize diagnosis combination clinical biological radiological arguments therefore required hence need identify multiple sclerosis biomarkers biomarkers target immunity detection oligoclonal bands measurement igg index cytokines physiopathological process bloodbrain barrier can broken event can identified measuring metalloproteinase activity diffusion gadolinium brain magnetic resonance imaging markers demyelination astrocyte microglial activity may also interest well markers neuronal damage mitochondrial status measurement different lipids plasma cerebrospinal fluid can also provide suitable information different lipids include fatty acids fatty acid peroxidation products phospholipids well oxidized derivatives cholesterol oxysterols oxysterols constitute new biomarkers providing information form multiple sclerosis outcome disease answer treatmentpmid33684483 doi101016 jjsbmb2021105870,1.0
patient provider insights impact multiple sclerosis mental health narrative review neurol ther 2021 apr 20 doi 101007 s40120021002409 online ahead printabstractmultiple sclerosis ms chronic disease immune system attacks central nervous system causing inflammation neurodegeneration people living ms may experience variety symptoms consequence process including many invisible symptoms internally manifested seen others invisible symptoms ms reviewed companion article mood mental health disorders particular concern due high prevalence significant impact patient quality life review showcase experiences patient authors alongside perspectives healthcare provider authors promote awareness common mental health conditions faced living ms depression anxiety adjustment disorder bipolar disorder psychosis suicidal ideation many conditions stem part increased stress levels many uncertainties come managing life ms exacerbated environment created coronavirus disease 2019 covid19 pandemic patientcentered interdisciplinary approach routine screening mental health changes referral specialists needed can normalize discussions mental health increase likelihood people living ms will receive support care need management techniques robust social support cognitive behavioral therapy mindfulnessbased interventions pharmacotherapy may implemented build resilience promote healthy coping strategies increasingly patients access telehealth options well digital apps mental health management taken together approaches form integrative care model people living ms benefit care medical professionals variety support networks resources selfmanagement techniques optimal mental health carepmid33877584 doi101007 s40120021002409,0.0
unexpected worsening progressive multifocal leucoencephalopathy following covid19 pneumonia j neurovirol 2021 apr 19 doi 101007 s13365021009802 online ahead printabstractprogressive multifocal leucoencephalopathy serious side effect natalizumab humanized monoclonal antibody approved treatment multiple sclerosis report case unexpected worsening natalizumabrelated progressive multifocal leucoencephalopathy following covid19 natalizumab discontinuation slight neurological improvement observed two months later patient admitted hospital neurological deterioration covid19 mild pneumonia except sarscov2 infection potential factors neurological worsening identified thus pose hypothesis sarscov2 instrumental progressive multifocal leucoencephalopathy deteriorationpmid33876412 doi101007 s13365021009802,0.0
identifying mirnas multiple sclerosis gray matter lesions correlate atrophy measures ann clin transl neurol 2021 may 12 doi 101002 acn351365 online ahead printabstractobjective multiple sclerosis ms inflammatory demyelinating neurodegenerative disease central nervous system cns though ms initially considered white matter demyelinating disease myelin loss cortical gray matter reported disease stages previously identified micrornas mirnas white matter lesions wmls detected serum ms patients however mirna expression profiles gray matter lesions gmls progressive ms brains understudiedmethods used combination global mirnas gene expression profiling gmls independent validation using realtime quantitative polymerase chain reaction rtqpcr immunoin situ hybridization immunohistochemistryresults compared matched myelinated gray matter gm regions identified 82 mirnas gmls 10 significantly upregulated 17 significantly downregulated among 82 mirnas 13 also detected serum importantly associated brain atrophy ms patients predicted target mrnas mirnas belonged pathways associated axonal guidance tgf signaling foxo signaling using stateoftheart human proteinprotein interactome network analysis mapped four key gm atrophyassociated mirnas hsamir149 hsamir20a hsamir29c hsamir25 target mrnas also changed gmlsinterpretation study identifies mirnas altered gmls progressive ms brains correlate atrophy measures mirnas also detected sera ms patients act markers gml demyelination mspmid33978322 doi101002 acn351365,1.0
neuroimmunology covid19 nervenarzt 2021 mar 2 doi 101007 s00115021010771 online ahead printabstractmany neuroimmunological diseases encephalopathy encephalitis myelitis acute disseminated encephalomyelitis adem occurred frequently infections severe acute respiratory syndrome coronavirus 2 sarscov2 indicates parainfectious postinfectious association likely underlying mechanisms include virustriggered overactivation immune system hyperinflammation cytokine storm potentially also development specific autoantibodies central nervous system cns tissue predominantly detected cerebrospinal fluid severely ill coronavirus disease 2019 covid19 patients contrast direct damage invasion sarscov2 brain spinal cord seem play relevant role susceptibility infection sarscov2 patients multiple sclerosis myasthenia neuroimmunological diseases including risk severe disease courses determined administered immunotherapy known risk factors age comorbidities diseaserelated degree disability therefore immunotherapy patients delayed discontinued contribution neuroimmunological mechanisms longterm sequelae survival covid19 illness fatigue impairment memory sleep dysfunction anxiety will require longterm clinical followup preferentially covid19 register studiespmid33651117 doi101007 s00115021010771,0.0
gut microbiome progressive multiple sclerosis ann neurol 2021 apr 19 doi 101002 ana26084 online ahead printabstractobjective investigate gut microbiome progressive multiple sclerosis ms relates clinical diseasemethods sequenced microbiota healthy controls relapsing remitting ms rrms progressive ms patients correlated levels bacteria clinical features disease including edss quality life brain mri lesions atrophy colonized mice msderived akkermansia induced experimental autoimmune encephalomyelitisresults microbiota diversity differed ms patients vs controls differ rrms vs progressive ms differ based disease modifying therapies disease status greatest effect microbiome diversity followed bmi race sex progressive rrms found increased clostridium bolteae ruthenibacterium lactatiformans akkermansia decreased blautia wexlerae dorea formicigenerans erysipelotrichaceae ccm unique progressive ms found elevated enterobacteriaceae clostridium g24 fcey decreased blautia agathobaculum several clostridium species associated higher edss fatigue scores contrary view elevated akkermansia ms detrimental role found akkermansia linked lower disability suggesting beneficial role consistent found akkermansia isolated ms patients ameliorated eae linked reduction rort+ il17 producing t cellsinterpretation microbiota alterations shared relapsing progressive ms identified unique bacteria associated progressive ms clinical measures disease furthermore elevated akkermansia ms may compensatory beneficial response ms microbiome article protected copyright rights reservedpmid33876477 doi101002 ana26084,0.0
pharmacokinetic biomarker study delayedrelease dimethyl fumarate subjects secondary progressive multiple sclerosis evaluation cerebrospinal fluid penetration effects exploratory biomarkers mult scler relat disord 2021 feb 24 51102861 doi 101016 jmsard2021102861 online ahead printabstractbackground biomarkers useful reliable measure disease activity many fields medicine axonal glial biomarkers multiple sclerosis ms applied often technology improving becoming increasingly reliable nonclinical studies shown dimethyl fumarate dmf cytoprotective antiinflammatory effects purpose study explore pharmacokinetics pk dmf measuring mmf active compound serum cerebrospinal fluid csf well relevant biomarker data patients secondary progressive ms pwspms whether objective evidence neuroprotection pwspms treated dmfmethods sixteen pwspms serum cerebrospinal fluid csf evaluation pk studies levels mmf various time points ingestion dmf csf biomarkers neurofilament light chain nfl glial fibrillary acidic protein gfap ubiquitin carboxyoterminal hydrolase isozyme l1 uchl1 total tau ttau measured baseline week 6 week 28 initiating dmf starting dose 120 mg twice daily 4 weeks followed maintenance dose 240 mg twice daily clinical correlation patients edss mri time periods made biomarkers four normal human volunteers csf studies biomarkers baselineresults pk data showed csf mmf concentration 11 plasma tmax plasma 5 hr tmax csf 7 hr biomarker data showed cs nfl lesser extent gfap uchl1 ttau showed relevant changes clinical data pwspms receiving dmf showed clinical improvements expanded disability status scale edss biomarker changes mri correlated clinical measures group pwspms observation periodconclusions pk data showed tmax csf mmf peaked 2 hours later plasma 11 measured csf mmf readily crossed blood brain barrier allowing potential direct penetration brain nfl csf levels lesser extent gfap csf levels showed correlation disease activity pwspms data suggest dmf may benefit reducing disease activity pwspms studied longer duration larger wellcontrolled studies warranted dmf reasonably well tolerated 3 16 patients discontinue dmf 6 weeks due persistent side effects nfl appeared clinically relevant biomarker brain mri group 28week study periodpmid33773271 doi101016 jmsard2021102861,0.0
bariatric metabolic surgery patients morbid obesity multiple sclerosis nationwide matched cohort study surg obes relat dis 2021 feb 17s15507289 21 000952 doi 101016 jsoard202102013 online ahead printabstractbackground despite association obesity multiple sclerosis ms little known regarding safety efficacy outcomes patients ms severe obesity undergoing metabolic surgeryobjectives aim present study evaluate early complications efficacy outcomes metabolic surgery patients severe obesity mssetting nationwide swedenmethods matched cohort study 196 patients ms diagnosis swedish ms register undergoing metabolic surgery gastric bypass sleeve gastrectomy registration scandinavian obesity surgery registry soreg matched 110 control group without ms diagnosis soreg 2stage matching procedure used exact match surgical method followed propensity score matching including age sex preoperative bmi surgical center surgical access year surgery hypertension diabetes sleep apnea dyslipidemia results weight loss 2 years surgery similar patients ms controls total weight loss 316 91 versus 318 92 p 735 significant differences seen either overall postoperative complication rate 79 versus 72 p 778 serious postoperative complications 37 versus 28 p 430 aspects healthrelated quality life hrqol improved groups less physical aspects hrqol patients msconclusion metabolic surgery safe efficient treatment severe obesity patients ms leads subsequent improvements hrqol studies addressing effects metabolic surgery msrelated symptoms neededpmid33753006 doi101016 jsoard202102013,0.0
aberrant multimodal brain networks patients antinmda receptor encephalitis cns neurosci ther 2021 mar 13 doi 101111 cns13632 online ahead printabstractaims explore largescale brain network alterations examine clinical neuropsychological relevance patients antinmethyldaspartate receptor nmdar encephalitismethods twentyfour patients antinmdar encephalitis 26 matched healthy controls hcs enrolled study based multimodal mri dataset individual morphological structural functional brain networks constructed compared two groups multiple levels associations clinical neuropsychological variables discriminant ability significant alterations studiedresults multimodal network analysis revealed antinmdar encephalitis mainly affected morphological structural networks subtle alterations observed functional networks intriguingly decreased network local efficiency observed morphological structural networks increased nodal centrality lateral orbital gyrus convergently observed among three types networks patients moreover alterations particularly structural networks accounted largely cognitive deficits patients distinguish diseased individuals hcs excellent performance area curve 0933 conclusions current study provides comprehensive view characteristic multimodal network dysfunction antinmdar encephalitis crucial establish new diagnostic biomarkers promising therapeutic targets diseasepmid33713553 doi101111 cns13632,0.0
global peginterferon beta1a tolerability management best practices nursefocused delphi approach neurol ther 2021 mar 24 doi 101007 s40120021002383 online ahead printabstractintroduction injection site reactions isrs flulike symptoms fls common patients relapsing forms multiple sclerosis ms treated peginterferon beta1a purpose delphi analysis explore peginterferon beta1a discontinuation rates across ms treatment centers obtain consensus effective mitigation management strategies isrs fls identify areas additional training education nurses patients improve treatment outcomesmethods modified delphi process international steering committee eight mscertified nurses developed two rounds surveys completed 262 188 ms nurses respectively representing nine countriesresults average nurses reported 25 30 patients treated peginterferon beta1a experienced isrs fls respectively discontinuation due severe isrs fls common first 6 months treatment yet followup visits typically took place 6 months peginterferon beta1a initiation preferred management strategies isrs included nonsteroidal antiinflammatory drugs rotation injection site whereas preferred management strategies fls included acetaminophen paracetamol hydration nutrition nurses 77 agreed additional education training isr fls management bolster confidence treating patients symptomsconclusion delphi respondents reached consensus isr fls management strategies can help inform treatment decisions results global delphi analysis indicate management isrs fls improved frequent followup visits individualized training educationpmid33761099 doi101007 s40120021002383,0.0
effects gait balance homebased active video game interventions persons multiple sclerosis systematic review mult scler relat disord 2021 mar 28 51102928 doi 101016 jmsard2021102928 online ahead printabstractbackground current coronavirus disease covid19 pandemic makes difficult obtain physical therapy rehabilitation centres particularly persons multiple sclerosis pwms population high risk since viral infections may contribute ms exacerbations relapses active video games way maintain physical therapy home part rehabilitation aim review summarise current best evidence effectiveness homebased active video games gait balance user compliance feasibility safety pwmsmethods searched studies five databases pubmed scopus cochrane cinahl science direct october 2020 selection studies extraction data methodological quality assessment pedro scale made independently two authors discussed third authorresults nine studies included systematic review found significant improvements balance results mixed concerning mobility physical activity gait homebased active video games feasible safe good compliance adherence methodological quality studies moderate pedro scale 53 2 conclusion overall homebased active video games found safe effective improving static dynamic balance pwms compliance good probably motivating enjoyable training active video games can relevant alternative physical rehabilitation home pwms future studies follow rigorous methodological standards larger sample sizes randomised controlled trials improve quality evidence include costeffectiveness analysispmid33845351 doi101016 jmsard2021102928,0.0
realworld propensity score comparison treatment effectiveness peginterferon beta1a vs subcutaneous interferon beta1a glatiramer acetate teriflunomide patients relapsingremitting multiple sclerosis mult scler relat disord 2021 apr 8 51102935 doi 101016 jmsard2021102935 online ahead printabstractbackground multiple diseasemodifying therapies dmts approved us food drug administration treatment relapsingremitting multiple sclerosis rrms separately conducted clinical trials peginterferon beta1a subcutaneous interferon beta1a sc ifn beta1a glatiramer acetate ga teriflunomide demonstrated efficacy reducing relapses headtohead phase iii clinical trials directly compared treatment efficacy peginterferon beta1a dmtsobjectives propensity scorebased comparison conducted treatment effectiveness peginterferon beta1a vs sc ifn beta1a ga teriflunomide among patients rrms identified large us administrative healthcare claims databasemethods adult patients 1865 years age 1 claim ms diagnosis november 2013 june 2017 1 claim peginterferon beta1a sc ifn beta1a ga teriflunomide november 1 2014 march 31 2017 identified ibm marketscan commercial database index date first claim patients dmt initiated patients 12 months insurance enrollment preindex baseline period 90 days postindex variable length followup period included patients grouped cohorts according index dmt patient demographics clinical characteristics evaluated propensity score matching psm separately conducted pairwise comparisons treatment effectiveness peginterferon beta1a dmt cohorts postindex followup period annualized relapse rate arr relapse defined hospitalization outpatient visit subsequent treatment annualized number length inpatient stays number claims durable medical equipment evaluatedresults psm 325 patients mean age 460 years peginterferon beta1a cohort compared 967 mean age 469 years sc ifn beta1a cohort likewise 564 patients mean age 474 years peginterferon beta1a 1688 mean age 476 years ga cohort finally 584 patients mean age 491 years peginterferon beta1a cohort 1742 mean age 490 years teriflunomide cohort postindex followup period arr significantly differ peginterferon beta1a sc ifn beta1a cohorts arr lower among patients treated peginterferon beta1a among treated ga least squares mean lsm estimate 025 vs 031 lsm ratio 0809 p0027 teriflunomide lsm estimate 026 vs 037 lsm ratio 0704 p0001 annualized mean number length inpatient stays mean number claims durable medical equipment postindex followup differ matched peginterferon beta1a ga cohorts peginterferon beta1a teriflunomide cohortsconclusion realworld comparative analysis patients similar patient characteristics treatment peginterferon beta1a associated lower arrs treatment either ga teriflunomide arrs differ among patients treated sc ifn beta1a also measured secondary outcomes differ study cohorts realworld data may help support decisionmaking treatment patients rrmspmid33882426 doi101016 jmsard2021102935,0.0
typed study natalizumab treatment pediatriconset multiple sclerosis portugal mult scler relat disord 2021 feb 24 51102865 doi 101016 jmsard2021102865 online ahead printabstractbackground significant proportion pediatriconset multiple sclerosis poms patients respond firstline diseasemodifying therapies clinical trials showed natalizumab effective safe adults limited clinical trial data children natalizumab currently prescribed offlabel poms aimed characterize effectiveness safety tolerability natalizumab poms cases treated portugal 2007 2018 methods data clinical records retrospectively collected poms cases treated natalizumab portugalresults twentyone patients included 14 67 female median age poms diagnosis 13 years old median duration treatment natalizumab 2 years 3 months median expanded disability status scale score decreased 15 10 24 months annualized relapse rate decreased 131 events patient year treatment natalizumab 0 12 months treatment 004 24 months gadoliniumenhancing lesions new enlarged t2 hyperintense lesions observed 8 8 patients 100 12 months 4 5 80 24 months one possible serious adverse event require dose adjustment five patients discontinued treatment due positive antijcv jc virus antibody jc serostatusconclusion natalizumab may effective safe diseasemodifying therapy poms results line data published adult population well similar observational studies pediatric populations regionspmid33714125 doi101016 jmsard2021102865,0.0
baicalein alleviates osteoarthritis protecting subchondral bone inhibiting angiogenesis synovial proliferation j cell mol med 2021 may 3 doi 101111 jcmm16538 online ahead printabstractosteoarthritis oa one frequent chronic joint diseases increasing life expectancy main characteristics disease loss articular cartilage subchondral bone sclerosis synovium inflammation physical measures drug therapy surgery mainstay treatments oa whereas drug therapies mainly limited analgesics glucocorticoids hyaluronic acids alternative therapies single therapeutic target oa joints baicalein traditional chinese medicine extracted scutellaria baicalensis georgi widely used antiinflammatory therapies previous studies revealed baicalein alleviate cartilage degeneration effectively acting articular chondrocytes however mechanisms involved baicaleinmediated protection oa completely understood consideration integrality arthrosis study found intraarticular injection baicalein ameliorated subchondral bone remodelling studies showed baicalein decrease number differentiated osteoblasts inhibiting preosteoblasts proliferation promoting preosteoblasts apoptosis addition baicalein impaired angiogenesis endothelial cells inhibited proliferation synovial cells taken together results implicated baicalein might effective medicine treating oa regulating multiple targetspmid33939310 doi101111 jcmm16538,0.0
activated microglia drive demyelination via csf1r signaling glia 2021 feb 23 doi 101002 glia23980 online ahead printabstractmicrogliosis prominent pathological feature many neurological diseases including multiple sclerosis ms progressive autoimmune demyelinating disorder precise role microglia parenchymal central nervous system cns macrophages demyelination relative contributions peripheral macrophages incompletely understood classical markers used identify microglia reliably discriminate microglia peripheral macrophages confounding analyses use genetic fate mapping strategy identify microglia predominant responders key effectors demyelination cuprizone cup model colonystimulating factor 1 csf1 also known macrophage colonystimulating factor mcsf secreted cytokine regulates microglia development survivalis upregulated demyelinated white matter lesions depletion microglia csf1r inhibitor plx3397 greatly abrogates demyelination loss oligodendrocytes reactive astrocytosis results cup treatment electron microscopy em serial block face imaging show myelin sheaths remain intact cup treated mice depleted microglia however cupdamaged myelin sheaths lost robustly phagocytosed uponrepopulation microglia direct injection csf1 cns white matter induces focal microgliosis demyelination indicating active csf1 signaling can promote demyelination finally mice defective adopting toxic astrocyte phenotype driven microglia nevertheless demyelinate normally upon cup treatment implicating microglia rather astrocytes primary drivers cupmediated demyelination together studies indicate activated microglia required can drive demyelination directly implicate csf1 signaling eventspmid33620118 doi101002 glia23980,1.0
quantitative mri texture analysis chronic active multiple sclerosis lesions magn reson imaging 2021 mar 23s0730725x 21 000485 doi 101016 jmri202103016 online ahead printabstractobjective recently increasing interest chronic enlarging chronic active multiple sclerosis ms lesions associated clinical disability however investigation dynamic lesion volume changes requires longitudinal mri data two time points aim study investigate application texture analysis ta baseline t1weighted 3d magnetizationprepared rapid acquisition gradientecho mprage images differentiate chronic active chronic stable ms lesionsmaterial methods identify chronic active lesions compared nonenhancing stable lesions two mprage datasets acquired 3 t mri baseline 12 months followup applied voxelguided morphometry vgm algorithm ta performed baseline mprage images 36 texture features extracted lesionresults overall 374 chronic ms lesions 155 chronic active 219 chronic stable lesions 60 ms patients included final analysis multiple texture features including discretized_histo_energy glcm_energy glcm_contrast glcm_dissimilarity significantly higher chronic active compared chronic stable lesions partial least squares regression yielded area curve 07 differentiate lesion typesconclusion results suggest multiple texture features extracted mprage images indicate higher intralesional heterogeneity however demonstrate fair accuracy differentiate chronic active chronic stable ms lesionspmid33771609 doi101016 jmri202103016,0.0
progression series patients relapsingremitting multiple sclerosis treated 7 years natalizumab using quot evidence disease activityquot parameter neurologia engl ed 2021 jun 36 5 346352 doi 101016 jnrleng202002001 epub 2020 feb 16abstractintroduction safety effectiveness natalizumab patients relapsingremitting multiple sclerosis rrms demonstrated clinical trials however due limitations trials important know condition behaves longterm clinical practice conditionsobjective determine longterm effectiveness natalizumab patients rrms means annual evaluation evidence disease activity neda parameter includes number relapses disability measured expanded disability status scale brain mri parameterspatients methods performed retrospective study patients rrms 3 centres treated one doses natalizumab year evaluated neda status safety based percentage patients discontinued treatment natalizumab experienced adverse reactionsresults study included 89 patients received treatment 2 4 years followup period 7 years natalizumab significantly reduces radiological clinical progression disease well annual rate relapses neda parameter demonstrates effectiveness drug values 7528 year one 6667 year 7 twentyfive patients 281 dropped median 4 years fourteen patients 56 dropped due appearance antijc virus antibodies either isolation associated another cause four dropouts 16 due treatment ineffectiveness one patient dying due progressive multifocal leukoencephalopathyconclusions natalizumab highly effective measured neda longterm remission parameterpmid34714232 doi101016 jnrleng202002001,0.0
animal models multiple sclerosis curr protoc 2021 jun 1 6 e185 doi 101002 cpz1185abstractanimal models high translational validity essential tools understanding disease pathogenesis development therapeutic strategies multiple sclerosis ms autoimmune demyelinating disease central nervous system characterized progressive neurological deficits socioeconomic burden experimental autoimmune encephalomyelitis eae extensively utilized animal model ms wellcharacterized rodent nonhuman primate variants eae model typically induced either active immunization myelinderived proteins peptides adjuvant passive transfer activated myelinspecific cd4+ t lymphocytes date eae model essential tool development least seven us food drug administration fda approved immunomodulatory drugs treatment ms including glatiramer acetate fingolimod natalizumab however translational validity eae model frequently compromised due poor study design inconsistent clinical scoring endpoints inappropriate statistical calculations single animal model accurately reflects complexity human ms pathogenesis beyond eae multiple additional animal models described including theilers murine encephalomyelitis virus cuprizoneinduced demyelination facilitate study pathogeninduced cns autoimmunity remyelination respectively overview summarizes several frequently used animal models ms highlights key factors significantly influence experimental outcome affect translational validity 2021 wiley periodicals llcpmid34170637 doi101002 cpz1185,1.0
role immune semaphorins pathogenesis multiple sclerosis potential therapeutic targets int immunopharmacol 2021 mar 20 95107556 doi 101016 jintimp2021107556 online ahead printabstractthe immune nervous systems possess highly intricate network synaptic connections shared messenger molecules exquisite communication ways allowing intercellular signal transduction semaphorins semas initially identified axonal guidance molecules development nervous system later found implicated also regulating immune system known case immune semas immunoregulatory semas increasingly molecules involved multiple aspects physiological pathological immune responses recently indicated take part various immunological disorders encompassing allergy cancer autoimmunity semas transduce signals connecting cognate receptors namely plexins neuropilins like sema3f found function inducer remyelination process whereas others like sema3a sema4d act inhibit process either directly indirectly besides sema4a crucial differentiation t helper type 1 th1 th17 cells potentially involved pathogenesis multiple sclerosis ms autoimmune disease central nervous system review aims reveal role immune semas pathogenesis ms animal model experimental autoimmune encephalomyelitis focusing therapeutic usages molecules treat neurodegenerative diseasepmid33756227 doi101016 jintimp2021107556,1.0
new frontiers pharmacologic obstructive sleep apnea treatment anarrative review sleep med rev 2021 mar 13 57101473 doi 101016 jsmrv2021101473 online ahead printabstractobstructive sleep apnea osa common form sleepdisordered breathing characterized intermittent partial complete closure upper airway sleep left untreated osa associated adverse cardiovascular outcomes hypertension coronary heart disease heart failure cardiac arrhythmia stroke death positive airway pressure pap often considered firstline treatment osa pap can effective reducing number obstructive apneas hypopneas impact prevention adverse cardiovascular consequences remains controversial treatment adherence often poor hence necessity novel treatment options help adhere positive airway pressure treatment different classes medications tested regards effect osa severity review 1 provides update epidemiology pathophysiology osa 2 outlines mechanistic rationale medication classes tested osa treatment 3 discusses effects medications osa several wakepromoting medications approved management persistent sleepiness despite osa treatment discussion symptomatic treatments outside scope review herein authors review current evidence pharmacological management osa provide future directionspmid33853035 doi101016 jsmrv2021101473,0.0
covid19 pandemic experience multiple sclerosis good bad neutral neurol ther 2021 apr 15 doi 101007 s40120021002418 online ahead printabstractintroduction current covid19 pandemic affected lives many paucity information impact people multiple sclerosis ms study sought gain insight impact current situation people ms factors influence thismethods 324 ms patients participated online crosssectional survey covid19 lockdown period mixed methods design used quantitative information collected msrelated factors well covid19 impact openended qualitative response looking reasons behind selfreported covid19 impactresults found 48 participants reported covid19 neutral impact lives 16 reported positive impact however 36 reported negative impact greater levels ms nonmsrelated worries higher levels bother related psychological cognitive symptoms fatigue groups reporting neutral positive impact significant predictors adversely affected group age type ms presence psychological symptoms antidepressant medication use time since diagnosis gender location living arrangements employment status predict impact openended responses explaining personal covid19 impact indicate coping strategies may contribute findings particular active problemfocused approaches reported majority people reported positive impact well third reported neutral impactconclusion findings suggest younger people progressive types ms psychological symptoms particularly vulnerable negative effects covid19 pandemic induced lockdown coping strategies provide insight findings reporting active problemfocused approaches seemingly faring better state coping strategies results also implications understanding like neurological conditions share many similarities ms best direct supportpmid33855692 doi101007 s40120021002418,0.0
#39 sleeping volcano erupt sooner later#39 lived experiences women multiple sclerosis childbearing age motherhood phenomenological qualitative study mult scler relat disord 2021 apr 18 51102938 doi 101016 jmsard2021102938 online ahead printabstractintroduction multiple sclerosis ms mainly involves women impacting many aspects related childbearing age maternity women ms can healthy pregnancies infants needs challenges concerns women ms considered order improve care pathway ensuring patientcentred approach therefore aim study explore personal experiences expectations fears women msmethods descriptive phenomenological study including women ms childbearing age pregnancy motherhood carried january april 2019 women enrolled ms centre snowball sampling healthcare network invited facetoface phone interview digitally audiorecorded fully transcribed two different sets semistructured interviews developed woman seeking pregnancy pregnant woman mother together anonymous form collect main sociodemographic data categorical data analysis inductively deductively processed 3 different researchers using creswell extension reduce subjective influences qda miner qualitative text analysis software usedresults following 6 deductive themes emerged 1 experience diagnosis ms 2 relationship partner children family 3 pregnancy 4 delivery 5 puerperium 6 care pathway experiences diagnosis can different women communication ms diagnosis appears opportunity strengthen emotional ties despite sorrow concerns reasons quarrels disagreements couple parents due overly protective supportive attitude participants reported difficulty conceiving pregnancy described state wellbeing devoid fears worries women experienced fatigue exhaustion especially second stage labour spontaneous delivery described empowering experience findings breastfeeding confirm healthcare professionals crucial role regarding initiation duration type breastfeeding often scarce education training topic together lack reliable scientific sources lead conservative approach healthcare providers communication consulting emerge indispensable skillsconclusion study provides better understanding ms impacts women life childbearing age pregnancy motherhood findings support importance provide quality tailored care women ms according empathetic patientcentred approach research comprehensive explorations mothers experiences different cultural contexts also partners offspring women mspmid33882427 doi101016 jmsard2021102938,0.0
systemic sclerosisassociated myositis features minimal inflammation characteristic capillary pathology acta neuropathol 2021 apr 17 doi 101007 s00401021023053 online ahead printabstractsystemic sclerosis represents chronic connective tissue disease featuring fibrosis vasculopathy autoimmunity affecting skin multiple internal organs skeletal muscles vasculopathy considered obliterative pathogenesis still poorly understood may partially due limitations conventional transmission electron microscopy previously conducted single patients aim study therefore precisely characterize immune inflammatory features capillary morphology systemic sclerosis patients suffering muscle weakness study identified 18 individuals underwent muscle biopsy muscle weakness myalgia cohort 367 systemic sclerosis patients performed detailed conventional immunohistochemical analysis largescale electron microscopy digitizing entire sections indepth ultrastructural analysis muscle biopsies 12 18 patients 67 presented minimal features myositis clear capillary alteration termed minimal myositis capillary pathology mmcp study provides novel findings systemic sclerosisassociated myositis first identified characteristic specific morphological pattern termed mmcp 67 cases 33 feature alterations characteristic overlap syndromes also reflected relatively homogeneous clinical picture among mmcp patients milder disease little muscle weakness low prevalence interstitial lung disease 20 diffuse skin involvement 10 cases either pulmonary arterial hypertension renal crisis second largescale electron microscopy introducing new level precision ultrastructural analysis revealed characteristic capillary morphology basement membrane thickening reduplications endothelial activation pericyte proliferation provide openaccess panandzoom analysis datasets enabling critical discussion data mining clearly highlight characteristic capillary pathology skeletal muscles systemic sclerosis patientspmid33864496 doi101007 s00401021023053,0.0
prenatal perinatal factors associated developing multiple sclerosis later life systematic review metaanalysis autoimmun rev 2021 apr 15102823 doi 101016 jautrev2021102823 online ahead printabstractobjective genetic environmental factors play roles multiple sclerosis ms etiopathogenesis relationship prenatal perinatal factors exposures future ms occurrence offspring remains controversial aimed review available evidence prenatal perinatal factors associated later ms occurrencemethod performed systematic search pubmed web science scopus inception october 2020 included original observational studies conducted human participants addressing association prenatal perinatal factors ms occurrence data extracted according prisma guideline adjusted odds ratio 95 confidence interval ci considered desired effect size heterogeneity evaluated cochrans q i2 publication bias assessed excluded gestational neonatal vitamin d level season birth latitude recently published systematic reviews metaanalyses subjectsresults overall 2306 records identified primary search excluding irrelevant studies evaluated 34 studies contributing data 100 prenatal perinatal factors associated increased decreased risk ms occurrence metaanalyses found statistically significant associations later ms occurrence offspring prenatal smoking exposure 101 95 ci 077134 mode delivery 090 95 ci 052156 birth order 085 95 ci 072100 maternal age 134 95 ci 088204 paternal age parents marital status time childbirth maternal preeclampsia toxemia forceps use birth weight plurality preterm birth studied factors none reported affect ms riskconclusion found prenatal smoking exposure mode delivery birth order maternal age affect risk future ms development moreover investigated factors reported affect ms risk offspring longitudinal studies needed confirm findingspmid33866064 doi101016 jautrev2021102823,0.0
smartphone applications assess gait postural control people multiple sclerosis systematic review mult scler relat disord 2021 apr 16 51102943 doi 101016 jmsard2021102943 online ahead printabstractbackground methods effectively assess gait balance impairments necessary guide interventions among people multiple sclerosis pwms smartphonebased evaluations becoming popular due ubiquitous use smartphones societyobjective determine current state smartphone applications assess gait balance among pwmsmethods two independent reviewers screened articles retrieved pubmed web science scopus cinahl sportdiscuss articles meeting eligibility criteria summarized qualitatively discussed participant characteristics validity reliability sensitivity specificity measures main results smartphonebased gait balance evaluations summarized methodological quality appraisal studies performed using quality assessment tool observational cohort crosssectional studiesresults eight articles included review studies present mostly low risk bias studies successfully tested use smartphone applications assessing gait balance among pwms total 75 studies evaluated validity 38 evaluated reliability sensitivity specificity smartphone applications assess gait balance studies except one found smartphone applications appropriately valid reliable sensitive specific assessing gait balance studies 88 reported pwms clinicians intended usersconclusion evidence supporting use smartphone applications assess gait balance among pwms future studies examine psychometric properties smartphonebased gait postural control assessments well sensitivity specificity improve interpretation resultspmid33873026 doi101016 jmsard2021102943,0.0
rabies vaccination multiple sclerosis relapse retrospective cohort study mult scler relat disord 2021 mar 18 51102906 doi 101016 jmsard2021102906 online ahead printabstractbackground studies assessing rabies vaccine rv tolerability persons multiple sclerosis ms conducted given lack safety data rv recommended essentially postexposure prophylaxis difficult administer effectively many rabiesendemic countries sought determine whether rv administration preexposure prophylaxis associated ms relapsemethods retrospective cohort study compared clinical courses ms patients year rabies vaccination year vaccination defined preexposure risk period three months thereafter exposurerisk period following nine months postrisk period adult ms patients immunized rv 2014 2018 available medical records twoyear window included primary outcome incidence symptomatic ms relapse exposurerisk period versus preexposure periodresults fiftyfive patients received least one dose rv 38 55 69 female mean age 385 years sd 92 21 38 patients experienced 24 relapses year vaccination three 5 experienced one relapse postvaccination exposurerisk period three others 5 experienced total four relapses subsequent postrisk period annualized relapse rates preexposure exposurerisk postrisk periods 044 022 010 respectively rate ratio exposurerisk preexposure periods 0509 95 ci 00981677 conclusions cohort rabies vaccination associated clinical ms relapse larger prospective studies needed confirm resultspmid33827005 doi101016 jmsard2021102906,0.0
conjugated linoleic acidcurcumin attenuates cognitive deficits oxidative stress parameters ethidium bromideinduced model demyelination neurotox res 2021 mar 13 doi 101007 s12640020003100 online ahead printabstractoxidative stress shown play important role pathogenesis multiple sclerosis ms curcumin cur antioxidant compound can potent treatment neurodegenerative diseases ms cur poor bioavailability therefore used nanoforms increase bioavailability present study effects cur conjugated linoleic acidcur linocur spatial memory oxidative stress putative animal model ms investigated fortynine adult male wistar rats 250 50 g randomly divided seven groups n 7 control sham ethidium bromide eb cur 20 40 g kg + eb linocur 20 40 g kg + eb groups following ms induction groups treated 5 consecutive days finally spatial memory levels oxidative stress parameters assessed treatment cur linocur two doses significantly improved spatial memory reduced oxidative stress parameters experimental models ms furthermore effects high dose 40 g kg linocur remarkable findings suggest microinjection cur synthetic form linocur significantly ameliorated spatial memory reduction oxidative stress markers brain studied animals rat model mspmid33713300 doi101007 s12640020003100,1.0
exercise leads metabolic changes associated improved strength fatigue people ms ann clin transl neurol 2021 may 6 doi 101002 acn351368 online ahead printabstractobjective goal exploratory study evaluate effects exercise intervention progressive resistance training prt metabolome people ms pwms link changes clinical outcomesmethods 14 pwms edss 40 13 age sexmatched healthy controls completed 12week inperson prt exercise intervention outcome measures included plasma metabolomics analysis cardiovascular fitness tests edss timed 25foot walk t25fw sixminute walk test 6mwt hip strength modified fatigue impact scale mfis identified changes metabolome prt intervention groups using individual metabolite abundance weighted correlation network defined metabolite module eigenvalues examined correlations changes metabolite modules changes various clinical outcomesresults groups prt intervention improved hip strength distance walked 6wmt speed walking fatigue mfis improved pwms fatty acid phospholipid sex steroid metabolism significantly altered prt pwms controls changes fatigue mfis score strongly inversely correlated hip strength moderately correlated change sex steroid metabolite module pwms similar relationship noted change dehydroepiandrosterone sulfate abundance sex steroid metabolite fatigue pwms also noted inverse correlation changes fatty acid metabolism cardiovascular fitness pwmsinterpretation prtinduced metabolic changes may underlie improved clinical parameters pwms may warrant investigation potential therapeutic targets future studiespmid33955210 doi101002 acn351368,0.0
covid19 emerging spinal cord complications systematic review mult scler relat disord 2021 mar 21 51102917 doi 101016 jmsard2021102917 online ahead printabstractbackground spinal cord complications associated coronavirus infectious disease 2019 covid19 widely reported purpose systematic review summarize far available pieces evidence documenting de novo novel severe acute respiratory syndrome coronavirus sarscov2 mediated spinal cord demyelinating diseases indeed spinal demyelinating disorders reported patients suffered covid19 rather people already living diagnosed undiagnosed primary demyelinating disordersmethods used existing prisma consensus statement data collected pubmed nih litcovid embase cochrane library databases well preprint servers medrxiv biorxiv prepreintsorg september 10 2020 using prespecified searching strategiesresults 21 selected articles case reports included 11 52 men 10 48 women mean age 467 180 neurological manifestations included weakness sensory deficit autonomic dysfunction ataxia cases elevated cerebrospinal fluid protein well lymphocytic pleocytosis found sarscov2 detected five 24 patients meanwhile 13 62 patients testing negative testing performed two cases one data unavailable nearly half cases n 9 associated isolated long extensive transverse myelitis letm whereas combination letm patchy involvement found two five patients isolated short segment involvement two patchy involvement furthermore concomitant demyelination brain spine reported six patients concerning prognosis patients improved mortality rate low n 2 10 conclusion spinal cord demyelination added plethora immune mediated neurologic complications associated covid19pmid33845350 doi101016 jmsard2021102917,1.0
serotoninergic system targeting multiple sclerosis prospective pathogenetic therapy mult scler relat disord 2021 mar 10 51102888 doi 101016 jmsard2021102888 online ahead printabstractserotonin 5hydroxytryptamine 5ht neurotransmitter mediates neuropsychological functions central nervous system cns recent studies shown modulatory effect 5ht gut microbiota functions play essential role developing cns inflammatory diseases finally 5ht direct mediator neuroimmune interaction article reviews literature data role 5ht regulation neuroinflammation multiple sclerosis ms influence 5ht selective serotonin reuptake inhibitors ssris experimental autoimmune encephalomyelitis eae ms pathogenesis well therapeutic potential serotoninergic drugs pathogenetic therapy ms discussedpmid33756440 doi101016 jmsard2021102888,0.0
symbol digit modalities test sdmt sensitive nonspecific ms lexical access speed memory information processing speed independently contribute sdmt performance mult scler relat disord 2021 apr 11 51102950 doi 101016 jmsard2021102950 online ahead printabstractbackground symbol digit modalities test sdmt sensitive metric neurocognitive function multiple sclerosis ms consistently interpreted measure information processing speed ips objective evaluate cognitive psychometric profile captured sdmt identify whether different cognitive processes independently underlie performancemethods three samples ms patients total n661 185 research patients ms center 370 clinical patients ms center 106 persons ms community completed objective assessments neuropsychological function across cognitive domains exploratory factor analysis efa used derive latent cognitive factor scores operationalize cognitive domain composite scores understand unique shared redundant contribution different cognitive domains sdmt performance using hierarchical multiple regression commonality analysisresults across three independent samples provide converging strong evidence cognitive domains memory ips rapid automatized naming lexical access speed jointly uniquely contribute sdmt performanceconclusion sdmt measures multiple cognitive processes likely explains high degree sensitivity cognitive change ms researchers clinicians interpret sdmt multifarious measure general cognition rather specific test ipspmid33887609 doi101016 jmsard2021102950,0.0
ozanimod relapsing multiple sclerosis pooled safety results clinical development program mult scler relat disord 2021 feb 15 51102844 doi 101016 jmsard2021102844 online ahead printabstractbackground ozanimod oral sphingosine 1phosphate receptor 1 5 modulator approved multiple countries treatment relapsing multiple sclerosis rms phase 3 trials ozanimod well tolerated superior interferon beta1a 30 g onceweekly reducing clinical radiologic disease activity objective integrated safety analysis evaluate safety extended ozanimod exposure participants rms clinical trials compare phase 3 trial datamethods report pooled incidence study durationadjusted incidence rates ir treatmentemergent adverse events teaes interim data cut january 31 2019 rms participants treated ozanimod data pooled phase 1 pharmacokinetic pharmacodynamic trial placebocontrolled phase 2 trial doseblinded extension 2 large activecontrolled phase 3 trials openlabel extension ole results compared pooled phase 3 trial dataresults data cutoff 2631 rms participants exposure ozanimod 092 mg mean 320 months 2787 exposure either ozanimod 046 092 mg mean 371 months irs per 1000 personyears py teae 7722 serious teaes 332 overall population similar phase 3 population 8961 312 respectively serious opportunistic infections seconddegree higher atrioventricular blocks electrocardiogram hepatic enzyme elevations declined time malignancy rates remained low longer exposure pulmonary function tests showed minimal reductions lung function seven ozanimodtreated participants comorbid risk factors confirmed macular edema including 3 ongoing oleconclusions safety results larger rms population greater ozanimod exposure demonstrated new safety concerns consistent phase 3 trial resultspmid33892317 doi101016 jmsard2021102844,0.0
lowfield portable brain mri cns demyelinating disease mult scler relat disord 2021 mar 18 51102903 doi 101016 jmsard2021102903 online ahead printabstracta lowfield 02 tesla portable mri scanner developed may address barriers mri people multiple sclerosis ms proof concept study imaged two participants central nervous system demyelinating disease standard 15 tesla mri portable mri scanner images demonstrate ability identify solitary demyelinating lesion early stage disease cortical atrophy chronic white matter changes late stage disease spite device limitations including border distortion lower image quality portable device important implications addressing barriers care people mspmid33780808 doi101016 jmsard2021102903,1.0
rate burden treatment sexual dysfunction multiple sclerosis case exercise training new treatment approach mult scler relat disord 2021 mar 2 51102878 doi 101016 jmsard2021102878 online ahead printabstractmultiple sclerosis ms prevalent immunemediated neurodegenerative disease central nervous system cns among adults united states worldwide disease results impairments physical psychological social functions compromise quality life review focuses sexual dysfunction including prevalence burden management persons ms sexual dysfunction defined sexual behaviors experiences characterized insufficient quality duration frequency sexual dysfunction occurs 4080 percent women 5090 percent men ms presence sexual dysfunction seemingly predicted psychological psychiatric issues depression anxiety sociodemographic dimensions older age unemployment lower socioeconomic status msrelated issues fatigue higher degree disability motor impairments sexual dysfunction persons ms associated decreased psychological psychosocial wellbeing impaired quality life limited research supporting pharmacological approaches managing sexual dysfunction ms make case exercise training based recent evidence randomized controlled trials ms putative mechanisms action targeted exercise training ms paper concludes providing research agenda deeper broader understanding exercise training sexual function mspmid33761411 doi101016 jmsard2021102878,0.0
association childhood maltreatment pain catastrophizing individuals immunemediated inflammatory diseases j psychosom res 2021 mar 30110479 doi 101016 jjpsychores2021110479 online ahead printabstractobjective childhood maltreatment associated pain catastrophizing childhood maltreatment pain catastrophizing prevalent certain immunemediated inflammatory disease imid populations however unknown whether childhood maltreatment contributes high rates pain catastrophizing imid cohorts assessed relationship childhood maltreatment pain catastrophizing individuals imid whether differed across imidmethods november 2014 july 2016 recruited individuals multiple sclerosis ms inflammatory bowel disease ibd rheumatoid arthritis ra participants completed childhood trauma questionnaireshort form pain catastrophizing scale hospital anxiety depression scale tested association childhood maltreatment pain catastrophizing using multivariable logistic regressionresults included 577 individuals imid ms 232 ibd 215 ra 130 overall 265 46 participants imid reported childhood maltreatment common type maltreatment emotional neglect childhood maltreatment associated pain catastrophizing 332 95 ci 189585 independent risk factors including sociodemographics symptoms anxiety depressionconclusion pain catastrophizing highly prevalent imid population strongly associated childhood maltreatment population interventions consider childhood maltreatment pain catastrophizing incorporated clinical management imid patientspmid33814193 doi101016 jjpsychores2021110479,0.0
phenomenon lhermitte pract neurol 2021 apr 13practneurol2020002918 doi 101136 practneurol2020002918 online ahead printno abstractpmid33850036 doi101136 practneurol2020002918,0.0
covid19 multiple sclerosis neuromyelitis optica spectrum disorder patients latin america covid19 ms nmosd patients latam mult scler relat disord 2021 mar 7 51102886 doi 101016 jmsard2021102886 online ahead printabstractbackground data regarding covid19 multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd patients latin americaobjective objective study describe clinical characteristics outcomes patients included relacoem latam registry ms nmosd patients infected covid19methods relacoem longitudinal strictly observational registry ms nmosd patients suffer covid19 dengue latam inclusion criteria registry either 1 biologically confirmed covid19 diagnosis based positive result covid19 polymerase chain reaction pcr test nasopharyngeal swab 2 covid19typical symptoms triad cough fever asthenia epidemic zone covid19 descriptive statistics performed demographic clinical variables cohort later stratified ms nmosd univariate multivariate logistic regression analysis performed identify variables associated hospitalizations intensive critical units icu admissionresults 145 patients included registry 15 countries 51 treating physicians total 129 89 ms patients 16 11 nmosd 814 patients confirmed covid19 186 suspected cases 23 158 patients hospitalized 9 62 required icu 5 34 died due covid19 ms patients greater age 117 95 ci 105 125 disease duration 139 95ci 114169 associated hospitalization icu nmosd patients greater age 543 vs 36 years p0001 increased edss 55 vs 29 p00012 disease duration 185 vs 103 years p0001 significantly associated hospitalization icuconclusion found ms patients age disease duration associated hospitalization icu admission requirement age disease duration edss associated nmosdpmid33744758 doi101016 jmsard2021102886,0.0
navigating dietary advice multiple sclerosis health expect 2021 apr 10 doi 101111 hex13226 online ahead printabstractbackground multiple sclerosis ms inflammatory demyelinating disease known cure numerous diets promoted reduce symptoms even cure ms despite insufficient evidence therapeutic diet qualitative studies exploring experiences people ms relation diet use theory explain findingspurpose explore experiences adults ms navigating dietary advice attitudes making dietary decisions needs regarding dietary resources educationmethods qualitative study conducted six focus groups people ms n 33 plus one spouse without ms groups audiorecorded transcribed verbatim primary analysis used general inductive approach thematic analysis secondary analysis aligned themes constructs selfdetermination theoryresults six themes emerged confusion seek dietary advice b scepticism towards national dietary guidelines c personalized approaches dietary change d barriers dietary changes e judging dietary changes work f wanting dietary guidelines msconclusion people ms highly motivated make dietary changes improve health selfdetermination theory explained people ms make dietary modifications varying levels motivation msspecific dietary resources nutrition education need incorporate ways increase autonomous forms motivation future dietary intervention studies use selfdetermination theory framework improve longterm adherence healthier dietspmid33838061 doi101111 hex13226,1.0
ponesimod first approval drugs 2021 may 3 doi 101007 s4026502101523z online ahead printabstractponesimod ponvory orally administered selective sphingosine1phosphate s1p receptor 1 s1p1 agonist developed janssen pharmaceutical companies johnson johnson treatment multiple sclerosis ms based results phase iii optimum trial ponesimod recently approved usa treatment relapsing forms ms received positive chmp opinion eu indication article summarizes milestones development ponesimod leading first us approvalpmid33939119 doi101007 s4026502101523z,0.0
restingstate brain network deficits multiple sclerosis participants evidence electroencephalography graph theoretical analysis brain connect 2021 mar 29 doi 101089 brain20200857 online ahead printabstractbackground multiple sclerosis ms chronic inflammatory disease leading demyelination axonal loss central nervous system causes focal lesions gray white matter however functional impairments brain networks disease still unspecified need clearer materials methods present study investigate restingstate brain network impairments ms participants comparison normal group using electroencephalography eeg graph theoretical analysis source localization method thirtyfour age gendermatched participants ms group normal group participated study recorded 5 min eeg restingstate eyes open condition participant one min 15 equal 4sec artifactfree segments eeg signals selected participant lowresolution electromagnetic tomography software employed calculate functional connectivity among whole cortical regions six frequency bands delta theta alpha beta1 beta2 beta3 graph theoretical analysis used calculate clustering coefficient cl betweenness centrality bc shortest path length spl smallworld propensity swp weighted connectivity matrices nonparametric permutation tests utilized compare measures groups results significant differences ms group normal group average bc swp found alpha band significant differences bc spread lobes conclusion results suggest restingstate brain network ms group disrupted local global scales eeg capability revealing impairmentspmid33780635 doi101089 brain20200857,1.0
covid19 patients multiple sclerosis treated cladribine tablets update mult scler relat disord 2021 mar 27 51102929 doi 101016 jmsard2021102929 online ahead printabstractbackground previously summarized outcomes 46 cladribine tablets cladt treated patients multiple sclerosis ms confirmed suspected covid19 reported merck kgaa global patient safety database report updates findings 15 january 2021 total 272 reported cases covid19 among cladt recipientsmethods case definitions confirmed covid19 diagnostic test positive suspected confirmatory test performed reported cases fulfilling criteria hospitalized medically significant fatal designated serious outcomes classified per usual pharmacovigilance practiceresults evaluable cohort comprised 261 patients confirmed covid19 n160 suspected n101 additional 11 patients symptoms compatible covid19 evaluated given negative diagnostic tests median time onset covid19 recent preceding cladt treatment course 162 days n139 outcomes recovered recovering n133 51 recovered resolved n19 7 died n1 04 reported missing pending n108 41 total cohort 40 15 experienced serious covid19conclusion results suggest cladttreated patients ms generally greater risk serious disease severe outcome covid19 compared general population patients ms acquired covid19pmid33813097 doi101016 jmsard2021102929,0.0
paving way towards effective treatment multiple sclerosis advances cell therapy cell mol immunol 2021 may 6 doi 101038 s4142302000618z online ahead printabstractmultiple sclerosis ms leading cause chronic neurological disability young middleaged adults affecting 25 million people worldwide currently therapeutics ms systemic immunosuppressive immunomodulatory drugs drugs unable halt reverse disease potential cause serious adverse events hence urgent need development nextgeneration treatments alone combination stop undesired autoimmune response contribute restoration homeostasis review analyzes current ms treatments well different cellbased therapies proposed restore homeostasis ms patients tolerogenic dendritic cells regulatory t cells mesenchymal stem cells vaccination t cells data collected preclinical studies performed experimental autoimmune encephalomyelitis eae model ms animals vitro cultures cells ms patients initial results phase ii clinical trials analyzed better understand parameters relevant obtaining efficient cellbased therapy mspmid33958746 doi101038 s4142302000618z,0.0
distinguishing diagnosis management sleep disturbance sleep disorders multiple sclerosis nurs clin north 2021 jun 56 2 157174 doi 101016 jcnur202102001abstractsleep critical issue quality life cognition safety among patients ms sleep disturbances poor sleep hygiene multiple sclerosis symptomology sleep disorders prevalent yet evaluation sleep screening sleep disorders inconsistent article presents commonly observed sleep disturbances disorders appropriate screening diagnostic considerations management options nurses providing care patients ms must recognize sleep important component care planning comprehensive sleep history appropriate screening instruments incorporated initial ongoing assessments referral sleep medicine providers indicatedpmid34023113 doi101016 jcnur202102001,0.0
pain multiple sclerosis neuromyelitis optica spectrum disorders schmerz 2021 may 25 doi 101007 s00482021005545 online ahead printabstractmultiple sclerosis neuromyelitis optica spectrum disorders autoimmune inflammatory diseases central nervous system can lead multitude neurological complaints pain syndromes pain may acute symptom disease exacerbation well chronic symptom whereby latter sometimes substantially reduces quality life etiology pain heterogeneous rapid differential diagnostic classification decisive order able initiate differentiated treatment strategy chronic pain must differentiated pain possible early symptom acute disease exacerbation classified detail individually treated include central neuropathic pain pain associated spasticity musculoskeletal pain due excess loading pain side effect immunotherapy context comorbidities treatment strategies often insufficiently evidencebased due lack datapmid34032887 doi101007 s00482021005545,0.0
vitamin d supplementation multiple sclerosis expert opinion based review current evidence expert rev neurother 2021 jun 1 doi 101080 1473717520211935878 online ahead printabstractintroduction vitamin d long known immunemodulating effects next function calcium metabolism consequence poor vitamin d status associated many diseases including multiple sclerosis ms epidemiological studies suggest association poor vitamin d status development ms poor vitamin d status associated relapses faster progression patients diagnosed msareas covered aim authors review role vitamin d supplementation treatment ms pubmed used review literature focus vitamin d supplementation trials metaanalyses msexpert opinion solid evidence support application vitamin d therapy based current available supplementation trials although promising results clinically isolated syndrome cis patients young ms patients early initial diagnosis authors recommend larger clinical trials selected patient groups preferable cis patients young patients time diagnosis using vitamin d3 supplements reach 100 nmol l level investigate effects vitamin d supplementation mspmid34058936 doi101080 1473717520211935878,0.0
inflammatory diseases central nervous system radiologe 2021 jun 61 6 575585 doi 101007 s0011702100863x epub 2021 jun 8abstractautoimmune inflammatory diseases central nervous system cns can diagnostic challenge despite advanced imaging techniques diagnostic errors can fatal consequences e g tumefactive lesions inappropriate treatment can exacerbate symptoms patients aim article provide help decision making selected autoimmune inflammatory diseases cns order fall diagnostic traps primary focus lesions neurocranium inflammatory diseases spinal cord already extensively discussed previous articlepmid34105011 doi101007 s0011702100863x,0.0
myelin oligodendrocyte glycoprotein antibodyassociated disease presentation diagnosis management pediatr ann 2021 jun 50 6 e254e258 doi 103928 193823592021051903 epub 2021 jun 1abstractpediatric demyelinating syndromes spectrum diseases affecting central nervous system past decade major advances made field including discovery antibodybased biomarkers treatment guidelines specific syndromes myelin oligodendrocyte glycoprotein mog antibodies first discovered thought biomarker multiple sclerosis ms however research shown mog positivity first episode pediatric demyelinating syndrome predictor course distinct ms article discusses clinical manifestations mog antibody associated disease key distinguishing features investigation treatment prognosis mog demyelinating diseases pediatr ann 2021 50 6 e254e258 pmid34115560 doi103928 193823592021051903,1.0
insomnia context neurological diseases fortschr neurol psychiatr 2021 jun 89 6 314328 doi 101055 a13090793 epub 2021 jun 18abstractthis article provides overview prevalence cause treatment insomnia common neurological diseases restless legs syndrome stroke multiple sclerosis parkinsons disease alzheimers disease additional focus bidirectional relationship sleep neurological disordersinsomnia prevalent frequently unrecognized context neurological diseases although widely known sleep relevant impact quality life general cerebral function particular sleep disorders receive little attention prevention treatment neurological diseasespmid34144624 doi101055 a13090793,0.0
serum endocan levels multiple sclerosis relapse remission eur rev med pharmacol sci 2021 jun 25 11 40914098 doi 1026355 eurrev_202106_26051abstractobjective endocan defined important marker inflammatory diseases vascular endothelial injury tumour progression cell adhesion angiogenesis study compared serum endocan creactive protein crp neutrophillymphocyte ratio nlr levels relapsingremitting multiple sclerosis rrms patients remission relapsepatients methods study included 53 rrms remission patients 30 rrms relapse postrelapse patients 44 healthy volunteers blood samples collected rrms patients remission control group twice rrms relapse patients relapsing another 1 month relapse endocan crp nlr levels rrms patients measured relapse 1 month relapse remission compared control group studied parameters compared disease duration relapse frequency expanded disability status scale edss score applied treatment lesion burden assessed using magnetic resonance imaging mri results endocan crp nlr levels significantly higher rrms group control group p 005 serum endocan levels found significantly higher rrms relapse group postrelapse control groups p 005 significant correlations disease duration edss score relapse frequency lesion burden mri endocan crp nlr values p 005 according correlation analysis statistically strong positive relationship mri lesion localisation edss score disease duration relapse frequency p 0001 conclusions endocan increase marker endothelial injury develops secondary inflammatory process ms patients can thus considered moderately good indicator relapsepmid34156688 doi1026355 eurrev_202106_26051,0.0
legal regulations institutional policies underlying parental leave graduate medical education j grad med educ 2021 jun 13 3 349354 doi 104300 jgmed20010831 epub 2021 apr 29no abstractpmid34178260 pmcpmc8207939 doi104300 jgmed20010831,0.0
covid19 pandemic changed multiple sclerosis clinical practice results nationwide provider survey mult scler relat disord 2021 mar 18 51102913 doi 101016 jmsard2021102913 online ahead printabstractbackground covid19 crisis created unanticipated changes health care delivery people living multiple sclerosis ms pandemics rapid evolution resulted knowledge gap covid19 affected ms clinical practice objective understand covid19 pandemic affected clinical practice patterns nationwide cohort ms clinicians across united statesmethods collaboration national multiple sclerosis society nmss developed 28item surveymonkeytm electronic questionnaire exploring ms specialists perceptions covid19 altered prescribe ms diseasemodifying therapies dmts provide telehealth services view issues affecting wellbeing including redeployment front lines covid19 care availability personal protective equipment ppe nmss staff sent recruitment email containing electronic survey link 188 clinicians serve regional nmss healthcare provider councils across us 86 457 ms specialist physiciansresults eightysix 188 potential respondents 457 32 us states completed survey including 45 physicians 41 neurologists 3 physiatrists 1 family physician 18 rehabilitation therapists 7 psychologists 6 nurse practitioners 4 social workers 2 physician assistants 2 nurses 2 health professionals disciplines 80 respondents working onsite health care setting believed adequate ppe 41 able distance safely others work nearly 10 respondents reported redeployed front lines covid19 patient care additional 169 anticipated redeployed among ms specialist physician subgroup nearly onethird reported using telemedicine provide 75 clinical care 167 believed covid19 changed prescribe dmts therapies prescribed often pandemic included ifns 286 prescribers natalizumab 238 glatiramer acetate 214 teriflunomide 19 dmts prescribed less often included alemtuzumab 643 prescribers cladribine 548 ocrelizumab rituximab 50 fingolimod siponimod 405 least patients pandemic ms specialists reported suspending certain dmts including alemtuzumab 214 prescribers ocrelizumab rituximab 167 cladribine 119 others reported extending dmt dosing intervals natalizumab 381 fingolimod siponimod 119 conclusions nationwide survey ms specialist physicians clinicians serving regional nmss healthcare provider councils across us reported profound changes delivering ms care covid19 pandemicpmid33839482 doi101016 jmsard2021102913,0.0
pediatric onset multiple sclerosis future challenge early diagnosis treatment presse med 2021 jul 12104069 doi 101016 jlpm2021104069 online ahead printabstractmultiple sclerosis major socioeconomical burden represents common cause nontraumatic neurological disability young adults 1 affects also children lower prevalence incidence remains major concern disability may occur later adulthood therefore absolute need earlier diagnosis treatment review focus objectives can achievedpmid34265375 doi101016 jlpm2021104069,0.0
alemtuzumab covid era mult scler relat disord 2021 mar 18 51102908 doi 101016 jmsard2021102908 online ahead printabstractbackground sarscov2 pandemic impact people multiple sclerosis pwms continues worry disease modifying therapies pwms can add severe risk infection compared general population alemtuzumab anticd52 monoclonal antibody one immunosuppressive drugs used multiple sclerosis ms case description present case covid19 infection occurred 24yearold woman ms treated alemtuzumab infection occurred 4 months administration first course alemtuzumab benign course subsequent development antibodies furthermore present brief review literature similar published casesdiscussion reviewed 17 articles concerning covid19 infection ms patients treatment alemtuzumab case screened cases severe course disease noted fatality observed systematic compilation observation comforts clinicians course covid19 infection despite alemtuzumab immunosuppressive treatment conclusions risk serious covid19 disease ms patients treated alemtuzumab unknown physicians need monitor carefully pwms treated alemtuzumab consider covid19 infection related relapse ms patients research recommended evaluate beneficialrisk profile alemtuzumab pandemic erapmid33812222 doi101016 jmsard2021102908,0.0
willingness vaccinated covid19 exploratory online survey portuguese cohort multiple sclerosis patients mult scler relat disord 2021 mar 5 51102880 doi 101016 jmsard2021102880 online ahead printabstractbackground little known ms patients acceptability covid19 vaccineobjective methods online survey conducted among ms patients study covid19 vaccine acceptability associated factorsresults conclusion among 256 participants 809 patients either definitely probably willing receive covid19 vaccine hesitant patients consider vaccinated physician recommendation older patients comorbidities seem willing get vaccinated moreover vaccine acceptability associated participants convictions concerns covid19 well previous vaccination practicespmid33740481 doi101016 jmsard2021102880,0.0
evidence disease activity3 neda3 status patients relapsing remitting multiple sclerosis evidence saudi cohort receiving mainly interferon mult scler relat disord 2021 mar 2 51102875 doi 101016 jmsard2021102875 online ahead printabstractbackground evidence disease activity neda composite surrogate assessing responsiveness various diseasemodifying treatments dmts patients relapsing remitting multiple sclerosis rrms addressing clinical well radiological disease activity despite rising prevalence multiple sclerosis saudi arabia sa lack evidence focusing important aspect management rrms study aimed identify prevalence neda3 status achievement patients rrms dmts mainly interferon describe factors affecting attainmentmethod retrospective crosssectional study carried king fahd university hospital obtaining institutional ethical approval electronic records 119 patients diagnosed rrms reviewed clinical manifestations initial presentation relapse starting treatment disability progression development new lesions followup magnetic resonance imaging documented assess neda3 status data analyzed using statistical package social sciences version 22results neda3 status achieved 41 336 patients femaletomale ratio patients 151 interferon ifn commonly prescribed dmt neda3 status achieved 309 patients receiving ifn mean baseline expanded disability status scale patients achieve neda3 2818 patients ataxia p 0001 sphincter disturbances p0002 infratentorial brain lesions p003 less likely achieve neda3 status involvement pyramidal cerebellar one system initial presentation frequent patients achieve neda3 status p0002 conclusion less one third total patients ifn dmt achieve neda3 status cohort patients agreement literature published west properly asses neda3 status dmts center due small sample size patients dmts recommend future studies including larger number patients dmts ifn significant differences identified two groups patients respect attainment neda3 status requires verification multicenter prospective studiespmid33691260 doi101016 jmsard2021102875,0.0
untreated patients multiple sclerosis study french expert centers eur j neurol 2021 mar 1 doi 101111 ene14790 online ahead printabstractbackground disease modifying therapies dmts impact relapses disease progression nonetheless many patients multiple sclerosis pwms remain untreated objective present study determine proportion untreated patients multiple sclerosis pwms followed expert centers france determine predictive factors nontreatmentmethods retrospective cohort study data extracted 38 centers participating european database multiple sclerosis edmus 12 15 2018 pwms seen least study period june 15 2016 june 14 2017 included results among 21 189 pwms age 471131 edss 3424 6 631 313 95ci307319 patients receiving dmt although patients relapsingremitting course n 11 693 likely receive dmt 148 95ci 142154 still untreated 68 never treated multivariate analysis among relapsingremitting pwms main factors explaining never treated 9 lesions brain mri 052 044061 lower edss 078 074082 patients progressive ms 504 secondary 642 primary progressive ms receive dmt study period 116 secondary 340 primary progressive ms never received dmtconclusion significant proportion pwms receive dmt even though treatments reimbursed healthcare system french patients result highlights unmet need current dmts large subgroup pwmspmid33650261 doi101111 ene14790,0.0
disease modifying therapies relapsingremitting multiple sclerosis systematic review network metaanalysis autoimmun rev 2021 apr 17102826 doi 101016 jautrev2021102826 online ahead printabstractobjective compare efficacy compliance uptodate disease modifying therapies dmts patients remittingrelapsing ms rrms methods searched pubmed embase cochrane library eligible studies annualized relapse rate discontinuation due adverse events aes assessed primary outcomes sensitivity analysis inconsistency detection performed evaluated whether exclusion highrisk studies affected validity risk bias assessed using cochranes riskofbias tool 2 surface cumulative ranking curve sucra used estimate rankings among different dmtsresults 21 studies included main report seven studies evaluated high risk therefore excluded exclusion highrisk studies affect validity evidence risk relapses dmts except betaseron 50 g significantly lower comparing placebo incompliance patients treated dmts significantly increased comparing placebo dimethyl fumarate ocrelizumab superiority improving mri outcomes ocrelizumab ofatumumab largest reduction risk disability progression 3 months referring sucra ofatumumab alemtuzumab natalizumab showed best efficacy complianceconclusion present study demonstrated hierarchy dmts treating rrms ofatumumab alemtuzumab natalizumab superiority respect effectiveness compliance studies required explore longterm effect dmts findings provide helpful information contribute clinical treatment decisionmakingpmid33878488 doi101016 jautrev2021102826,0.0
rare case progressive malignant triton tumor rare somatic mutation tsc2 gene anticancer res 2021 jun 41 6 30293036 doi 1021873 anticanres15085abstractbackground malignant triton tumor mtt rare subtype malignant peripheral nerve sheath tumor additional rhabdomyolysis differentiation shows rapid progression poor clinical outcomescase report report case adult male metastatic mtt despite extensive counseling patient initially refused recommended treatment upon disease progression patient admitted institution multiple distant organ metastases found patient underwent aboveknee amputation followed palliative chemotherapy patient died months later due rapid disease progressionconclusion knowledge first report case mtt multiple splenic metastases also describe first finding frameshift mutation tuberous sclerosis complex 2 tsc2 gene patient mtt limited clinical experience lack clinical trials effects chemotherapy radiation therapy mtt remain controversial however given aggressive nature tumors tendency early recurrence metastasis prompt diagnosis early surgical treatment crucial best outcomespmid34083294 doi1021873 anticanres15085,0.0
del1 potential therapeutic target inflammatory autoimmune disease expert rev clin immunol 2021 apr 1914 doi 101080 1744666x20211915771 online ahead printno abstractpmid33870840 doi101080 1744666x20211915771,0.0
giant bilateral angiomyolipoma kidney ann r coll surg engl 2021 may 6 doi 101308 rcsann20207036 online ahead printabstractangiomyolipoma benign solid renal neoplasm giant angiomyolipoma 10cm size can grow huge proportions case appears third largest angiomyolipoma largest among bilateral giant renal angiomyolipoma indexed literature 26yearold man presented large right abdominal swelling past three years occupying right flank iliac region extending beyond midline computed tomography abdomen revealed large welldefined mass right side abdomen crossing midline measuring 35 20 12cm left kidney showed similar fatty lesion 14 6cm findings consistent angiomyolipoma evaluation tuberous sclerosis magnetic resonance imaging brain demonstrated multiple subependymal nodules giant renal angiomyolipoma uncommon tumour bilateral giant angiomyolipoma rare entity preoperative embolisation helps reducing size tumour case giant bilateral angiomyolipoma evaluation tuberous sclerosis always donepmid33955281 doi101308 rcsann20207036,0.0
new concepts immunology multiple sclerosis presse med 2021 sep 18104072 doi 101016 jlpm2021104072 online ahead printabstractmultiple sclerosis ms chronic inflammatory immunedriven demyelinating disease central nervous system cns past decade major advances made understand development ms well progressive stage discuss emerging concepts immunology ms including growing interest involvement gut microbiota recent pathological concepts progression phase finally present immunotools recently available contribute better understand diversity function immune systempmid34547375 doi101016 jlpm2021104072,1.0
multiple sclerosis patient cryopyrinassociated autoinflammatory syndrome evidence autoinflammation common link clin immunol 2021 may 1108750 doi 101016 jclim2021108750 online ahead printabstractthe coexistence autoinflammatory syndrome demyelinating disorder rare occurrence raising question whether pathophysiological connection describe case man symptoms cryopyrinassociated periodic syndrome caps since infancy later developed multiple sclerosis ms caps genetically confirmed inhibition interleukin1 il1 anakinra led swift resolution caps symptoms also combination teriflunomide clinical imaging improvement ms vitro studies showed upon caps flare patients peripheral neutrophils released neutrophil extracellular traps nets decorated il1 net release markedly decreased following anakinrainduced remission caps taking account growing evidence involvement il1 experimental models ms rare patient case suggests role neutrophils nets il1 ms studiedpmid33945870 doi101016 jclim2021108750,1.0
cognitive dysfunction fatigue relapses taking better look mult scler 2021 jun 27 7 981982 doi 101177 1352458520986957no abstractpmid34018882 doi101177 1352458520986957,0.0
cross national comparison medical students#39 attitudes beliefs medical cannabis application pain management complement ther med 2021 apr 14102720 doi 101016 jctim2021102720 online ahead printabstractobjectives examine attitudes beliefs medical cannabis mc specifically application pain management across medical students israel thailanddesign crosssectional survey measured attitudes beliefs mc participants additionally asked rate perceived efficacy mc different medical conditions related pain arthritis chronic pain fibromyalgia multiple sclerosis pearsons chisquared test used compare students participating universitiesresults 430 medical students participated 379 n 163 israel 621 n 267 thailand personal cannabis use reported 556 israeli 69 thai students p 001 israeli secular students compared thailand likely recommend mc patient treatment less concerned serious physical mental health risks inclined support legalization recreational cannabis israeli students reported permissive attitudes toward mc reported feeling less prepared answer patient client questions mc thai counterpartsconclusions findings study accentuate need curriculum designed around mc use promote students preparedness serve patients pain medical conditions may benefit mc usepmid33864906 doi101016 jctim2021102720,0.0
effect pelvic floor exercise program incontinence sexual dysfunction multiple sclerosis patients int urol nephrol 2021 feb 23 doi 101007 s1125502102804y online ahead printabstractpurpose multiple sclerosis ms chronic neuroinflammatory disease central nervous system involves different neurological areas addition lower urinary tract symptoms luts sexual dysfunction sd psychopathological effects ms sometimes seriously impairs quality life qol hypothesize pelvic floor exercise program pfep improve bladder sexual function depression qol ms patientsmethods patients diagnosed ms completed incontinence questionnaire short form iciqsf beck depression inventory bdi multiple sclerosis quality life54 msqol54 questionnaire either female sexual function index fsfi sexual health inventory men shim maximum bladder volumes mbv postvoiding residual pvr volumes measured using ultrasonography patients regularly completed pfep 12 weeks asked fill questionnaires mbv pvr remeasuredresults seventytwo patients relapsingremitting multiple sclerosis rrms included study fortytwo 583 rrms patients reached end study patients postpfep average mbv statistically increased p 001 contrast statistically significant difference found pvr p 02 exercise fsfi values women increased p 002 iciqsf bdi values rrms patients statistically decreased p 0004 p 001 respectively improvement msqol54 score p 005 conclusion pfep causes reduction luts enhancing mbv rrms patients can seen investment future terms reducing depression ms patients preventing delaying sd womenpmid33620664 doi101007 s1125502102804y,0.0
role extracellular vesicles neurodegenerative diseases prog neurobiol 2021 feb 19102022 doi 101016 jpneurobio2021102022 online ahead printabstractextracellular vesicles evs heterogeneous cellderived membranous structures arise endosome system directly detach plasma membrane recent years many advances made understanding clinical definition pathogenesis neurodegenerative diseases translation effective treatments hampered several factors current research indicates evs involved pathology diseases alzheimers disease ad parkinsons disease pd multiple sclerosis ms amyotrophic lateral sclerosis als huntingtons disease hd besides evs also involved process myelin formation can also cross bloodbrain barrier reach sites cns injury suggested evs great potential novel therapy treatment neurodegenerative diseases reviewed advances understanding role evs neurodegenerative diseases addressed critical function evs cns also outlined physiological mechanisms evs myelin regeneration highlighted therapeutic potential evs neurodegenerative diseasespmid33617919 doi101016 jpneurobio2021102022,1.0
urokinase cx3cl1 ccl2 trail il18 induced interferon treatment acta neurol scand 2021 feb 24 doi 101111 ane13400 online ahead printabstractobjective identify serum proteins associated ms affected interferon beta treatmentmethods plasma samples 29 untreated relapsingremitting ms patients 15 healthy controls investigated multiplexed panel containing 92 proteins related inflammation followup samples available 13 patients 1 3 months initiation treatment interferon beta1aresults ten proteins differentially expressed ms patients five altered treatment ifn 1a upa cx3cl1 ccl2 trail il18conclusion ccl2 trail confirmed modulated interferon beta treatment ms novel findings now report upa cx3cl1 differentially expressed ms increased ifnbeta1a treatment conflicting results reported interferon beta affects il18pmid33626181 doi101111 ane13400,0.0
progressive multifocal leukoencephalopathy elderly immunocompetentappearing patient relevance lselectin cd62l expression immunosenescence clin neurol neurosurg 2021 apr 1 205106625 doi 101016 jclineuro2021106625 online ahead printabstractprogressive multifocal leukoencephalopathy pml attributed reactivation john cunningham virus jcv central nervous system result immunosuppression low lselectin cd62l expression cryopreserved tcells advocated biomarker natalizumab related pml patients relapsingremitting multiple sclerosis rare case pml elderly patient without known factors immunosuppression immunomodulation hereby presented tcell lselectin expression levels serum antijcv antibody index evaluated order explore mechanistic insight pathways presumably contribute towards pml development rare clinical settingpmid33892220 doi101016 jclineuro2021106625,0.0
ahsct superior alemtuzumab maintaining neda improving cognition multiple sclerosis ann clin transl neurol 2021 may 5 doi 101002 acn351366 online ahead printabstractobjective autologous hematopoietic stem cell transplantation ahsct increasingly recognized potential therapy patients highly active multiple sclerosis ms study aims assess outcome differences disease activity ms patients treated either ahsct alemtuzumabmethods conducted monocentric registrybased cohort study recording clinical course edss relapses mri parameters new t2 lesions neuropsychological assessment 19 ms patients receiving ahsct 21 patients receiving alemtuzumab 2007 2018 used survival analyses evidence disease activity neda primary objective defined edss progression relapse new t2 lesion mri secondary objectives edss improvement neurocognitive performanceresults treatment groups similar respect age gender disability neurocognitive performance except significantly longer disease duration alemtuzumab group mean followup 588 range 29140 months ahsct group compared 276 range 1152 months alemtuzumabtreated group observed significantly patients maintaining neda ahsct group p 0048 compared alemtuzumabtreated patients furthermore 37 ahsct patients showed improvement edss compared none alemtuzumabtreated group p 0033 note cognitive function significantly improved ahscttreated patientsinterpretation ahsct suppresses inflammatory activity effectively alemtuzumab might enable improvement overall disability cognition mspmid33949790 doi101002 acn351366,0.0
ms rare ebvseronegative children cns inflammatory demyelination ann neurol 2021 mar 11 doi 101002 ana26062 online ahead printabstractalthough epsteinbarr virus ebv hypothesized prerequisite multiple sclerosis ms 15 children diagnosis ms reported ebvseronegative reevaluating 25 ebvseronegative children 189 pediatric patients diagnosis clinically isolated syndrome ms found antimyelin oligodendrocyte glycoprotein mog antibody 11 25 44 ebvseronegative 9 164 55 p 0001 ebvseropositive patients critical review ms remained plausible diagnosis four 14 ebvseronegative mog antibodynegative patients children mslike presentation ebv seronegativity alert clinicians consider diagnoses ms especially mogantibody disease article protected copyright rights reservedpmid33704815 doi101002 ana26062,1.0
impairment time perception patients multiple sclerosis somatosens mot res 2021 mar 916 doi 101080 0899022020211879777 online ahead printabstractobjective objective study examine time perception impairment multiple sclerosis ms patientsmethod study performed 60 ms patients 60 agematched healthy people estimation production tests carried standard personal laptop computer participants aware count seconds start command stop stop command outcome measure ratio estimated duration target 7 s 32 s 58 s one estimation test produced duration target 7 s 32 s 58 s one production test time duration repeated three times production estimation testsresults found significant difference estimation test 7 s 32 s 58 s production test 7 s 32 s 58 s ms group healthy control group p 05 observed patients ms higher deviation target time compared control group found difference statistically significant p 05 high negative correlation estimation production tests ms patientsconclusion conclusion data suggests time estimation production disturbed ms patients cognitive rehabilitation required thempmid33719839 doi101080 0899022020211879777,0.0
trem2 expression brain biological fluids prion diseases acta neuropathol 2021 apr 21 doi 101007 s00401021022961 online ahead printabstracttriggering receptor expressed myeloid cells 2 trem2 innate immune cell surface receptor regulates microglial function involved pathophysiology several neurodegenerative diseases soluble form strem2 results shedding trem2 ectodomain role trem2 prion diseases group rapidly progressive dementias remains elucidated present study analysed expression trem2 main sheddase adam10 brain sporadic creutzfeldtjakob disease scjd patients evaluated role csf plasma strem2 potential diagnostic marker prion disease data indicate compared controls trem2 increased scjd patient brains mrna protein levels regional subtype dependent fashion expressed subpopulation microglia contrast adam10 increased protein mrna level restricted neuronal expression elevated csf strem2 found scjd genetic cjd mutations e200k v210i prion protein gene prnp iatrogenic cjd compared healthy controls hc auc 078090 neurological controls auc 073085 csf strem2 unchanged fatal familial insomnia strem2 csf cases alzheimers disease multiple sclerosis significantly altered series csf strem2 concentrations scjd prnp codon 129 subtyperelated correlate csf 1433 positivity totaltau ykl40 increase disease progression plasma strem2 increased scjd compared hc auc 080 displaying positive correlations plasma totaltau neurofilament light ykl40 conclude comparative study trem2 brain biological fluids prion diseases reveals trem2 altered human prion diseases potential value target engagement patient stratification disease monitoringpmid33881612 doi101007 s00401021022961,0.0
relationship walking speed energetic cost walking persons multiple sclerosis healthy controls systematic review neurorehabil neural repair 2021 apr 1315459683211005028 doi 101177 15459683211005028 online ahead printabstractbackground persons multiple sclerosis pwms experience walking impairments characterized decreased walking speeds healthy subjects selfselected walking speed energetically optimal pwms energetically optimal walking speed remains underexposed therefore review aimed determine relationship walking speed energetic cost walking cw pwms compared healthy subjects thereby assessing walking speed lowest energetic cost unclear whether cw pwms differs overground treadmill walking reported healthy subjects second review aim compare conditionsmethod pubmed web science systematically searched studies assessing pwms reporting walking speed converted meters per second reporting oxygen consumption included study quality assessed modified national heart lung blood institute checklist relationship cw walking speed calculated secondorder polynomial function compared groups conditionsresults twentynine studies included n 1535 pwms 8 included healthy subjects n 179 healthy subjects pwms showed similar energetically optimal walking speed 144 m s cw 016 compared 014 ml o2 kg m healthy subjects optimal walking speed treadmill 148 m s compared 128 m s overground walking similar cwconclusion overall cw elevated pwms similar energetically optimal walking speed compared healthy subjects treadmill walking showed similar optimal cw higher speed compared overground walkingpmid33847188 doi101177 15459683211005028,0.0
underutilization contraception young females demyelinating disorders mult scler relat disord 2021 mar 9 51102881 doi 101016 jmsard2021102881 online ahead printabstractbackground demyelinating disorders young females frequently treated immunomodulatory therapy often unknown risks fetuses pregnancy spite literature population use contraception objective determine rate use contraception used realworld cohort pediatric patients immunotherapy demyelinating diseasesmethods retrospective multicenter chartbased review performed inclusion criteria female gender use immunotherapy demyelinating disorder age 11 yearsresults fiftysix female patients identified average age 154 years common demyelinating disorders multiple sclerosis n 33 59 common treatments rituximab n 18 32 dimethyl fumarate n 13 23 ivig n 11 20 fingolimod n 11 20 overall 16 n 9 patients used contraception point immunotherapy regimen hispanic patients accounted 41 cohort uniformly contraceptives p 0 02 contraceptive use impact arr disease p 045 conclusions contraceptive use young females demyelinating disorders less 1 3rd general population particular discrepancies persons hispanic latino descentpmid33730609 doi101016 jmsard2021102881,1.0
depression multiple sclerosis one approach management enough mult scler relat disord 2021 mar 18 51102904 doi 101016 jmsard2021102904 online ahead printabstractbackground major depression disorder mdd severe depression symptoms highly prevalent multiple sclerosis ms depression can worsen symptoms ms associated significantly reduced quality life increased risk suicide currently goldstandard single treatment available depression ms pharmacotherapy cognitive behavior therapy cbt exercise training individually moderately yet incompletely efficacious managing depression general population mspurpose review provides overview evidence metaanalyses systematic reviews current treatments depression persons ms review develops rationale using combinatory treatment approach persons msmethods performed narrative review metaanalyses systematic reviews regarding current state evidence three common treatments depression persons ms ie antidepressant medication cognitivebehavior therapy exercise training provide concise assessment overall effect treatments depression general population persons ms note shortcomings research treatments depressionconclusion single goldstandard treatment depression ms proposed combinatory treatments considered management depression ms however paucity evidence use combinatory therapy depression outcomes persons ms supports direct examination feasibility efficacy combinatory approaches mdd mspmid33780807 doi101016 jmsard2021102904,0.0
machine learning diagnosis disability prediction multiple sclerosis using optical coherence tomography comput biol med 2021 apr 26 133104416 doi 101016 jcompbiomed2021104416 online ahead printabstractbackground multiple sclerosis ms neurodegenerative disease affects central nervous system especially brain spinal cord optic nerve diagnosis disease complex process generally requires lot time addition treatments applied without information disability course ms patient two reasons objective study improve ms diagnosis predict longterm course disability ms patients based clinical data retinal nerve fiber layer rnfl thickness measured optical coherence tomography oct material methods total 104 healthy controls 108 ms patients 82 10year followup enrolled classification algorithms multiple linear regression mlr support vector machines svm decision tree dt knearest neighbours knn nave bayes nb ensemble classifier ec long shortterm memory lstm recurrent neural network tested develop two predictive models ms diagnosis model ms disability course prediction modelresults ms diagnosis best result obtained using ec accuracy 877 sensitivity 870 specificity 885 precision 887 auc 08775 line good performance accuracy 854 using knn 844 using svm longterm prediction ms disability course lstm recurrent neural network appropriate classifier accuracy 817 sensitivity 811 specificity 822 precision 789 auc 08165 use mlr svm knn also showed good performance auc 08 conclusions study demonstrated machine learning techniques using clinical oct data can help establish early diagnosis predict course ms advance help clinicians select specific treatments ms patient therefore findings underscore potential rnfl thickness reliable ms biomarkerpmid33946022 doi101016 jcompbiomed2021104416,0.0
rehabilitation multiple sclerosis 2020 presse med 2021 may 11104066 doi 101016 jlpm2021104066 online ahead printabstractpatients multiple sclerosis despite advances therapy often suffer locomotor impairment limits mobility affect quality life rehabilitation part treatment ms shown beneficial effects numerous studies traditional rehabilitation techniques remain limelight new technologies emerging make possible improve management disabling symptoms aim update synthesize new therapy techniques proposed rehabilitation patients multiple sclerosis according symptoms balance gait upper limb disorders fatigue spasticity disease progression published past 5 years regard balance walking disorders neuromotor rehabilitation physical exercise rhythmic auditory stimulation gait robot training exergaming effective physical exercise shown positive effect fatigue management spasticity improved classic rehabilitation techniques however noninvasive brain stimulation promising rehabilitation upper limb dysfunctions uses various effective techniques repetition functional tasks real virtual situations case severe disability arm robots can used relearn impaired movement action observation training real virtual situations also effective finally certain conditions constraint induced movement therapy proposed effects rehabilitation positive pyramidal symptoms fatigue also increase neuroplasticity perhaps neuroprotective effect shown studiespmid33989721 doi101016 jlpm2021104066,1.0
recent advances optic nerve magnetic resonance imaging postprocessing magn reson imaging 2021 mar 19s0730725x 21 000461 doi 101016 jmri202103014 online ahead printabstractthe optic nerve known one largest nerve bundles human central nervous system many studies optic nerve imaging postprocessing provided insights pathophysiology optic neuritis related multiple sclerosis neuromyelitis optica spectrum disorder glaucoma lebers hereditary optic neuropathy many challenges optic nerve imaging due morphology nerve course optic chiasm mobility due eye movements high signal cerebrospinal fluid orbital fat surrounding optic nerve recently many advanced fast imaging sequences used postprocessing techniques attempts produce higher resolution images optic nerve evaluating various diseases magnetic resonance imaging mri one common imaging methodologies optic nerve review paper will focus recent mri advances optic nerve imaging explain several postprocessing techniques used analysis optic nerve images finally challenges potential future optic nerve studies will discussedpmid33753137 doi101016 jmri202103014,0.0
transcriptional regulator bob1 molecular mechanisms emerging role chronic inflammation autoimmunity autoimmun rev 2021 apr 14102833 doi 101016 jautrev2021102833 online ahead printabstractlymphocytes constitute essential potent effector compartment immune system therefore development functions must strictly regulated avoid inappropriate immune responses autoimmune reactions several lines evidence genetics eg association multiple sclerosis primary biliary cirrhosis human expression studies eg increased expression target tissues draining lymph nodes patients autoimmune diseases animal models eg loss functional protein protects animals development collageninduced arthritis experimental autoimmune encephalomyelitis type 1 diabetes bleomycininduced fibrosis strongly support causal link aberrant expression lymphocyterestricted transcriptional regulator bob1 development autoimmune diseases review summarize current knowledge unusual structural functional plasticity bob1 stringent regulation expression pivotal role bob1 plays shaping b tcell responses discuss recent developments highlighting significant contribution bob1 pathogenesis autoimmune diseases leverage knowledge target regulator treat autoimmune tissue inflammationpmid33864944 doi101016 jautrev2021102833,0.0
serum malondialdehyde lipid peroxidation marker multiple sclerosis patients relation disease characteristics mult scler relat disord 2021 apr 9 51102941 doi 101016 jmsard2021102941 online ahead printabstractintroduction oxidative stress suggested play key role pathogenesis multiple sclerosis ms clinical data oxidative stress markers ms patients influence clinical radiologic characteristics disease inconsistent aim study assess serum levels malondialdehyde mda measure lipid peroxidation ms patients relation disease characteristics methods case control study included 120 patients clinically definite relapsing remitting multiple sclerosis rrms compared 120 age sex matched healthy controls mda levels measured using thiobarbituric acid reactive substances tbars assay results mda levels significantly higher patients ms control p0001 especially relapse mda levels higher patients taking disease modifying therapy dmt taking interferon ifn mda levels significantly correlate expanded disability status scale edss p0001 conclusions results study can provide evidence incrimination oxidative stress ms pathogenesis disease disability support use antioxidants new target treatment focuses neutralizing free radicals increases antioxidant capacitypmid33895606 doi101016 jmsard2021102941,0.0
recurrence disease activity fingolimod discontinuation older patients previously stable treatment mult scler relat disord 2021 mar 21 51102918 doi 101016 jmsard2021102918 online ahead printabstractbackground discontinuing fingolimod fty older patients growing concern little evidence supporting decision pursue treatment reasonable doubt disease reactivation withdrawalobjective estimate incidence recurrence disease activity rda rebound fty withdrawal patients older 50 yearsmethods retrospective analysis ms patients clinic discontinued fty least 6 months treatment according disease activity fty age discontinuation rda defined occurrence either clinical mri activity 6 months fty withdrawal rebound levels disease activity surpassed pretreatment activityresults 128 patients discontinued fty since 2011 352 patients experienced evidence disease activity 125 rebound incidence rda rebound different among individuals persistent disease activity fty stopped fty reasons inefficacy rda 255 vs 205 p 0353 rebound 145 vs 11 p 0596 negative predictive factors rda younger age disease onset p 0036 highly active disease baseline p 0003 previous treatment ntz p 0013 older age fty discontinuation reduce risk rda patients previously stable treatment 0972 95 ci 08711085 p 0613 although incidence rda rebound half less older patients 365 50 vs 19 50 yearold p 0174 none patients 60 experienced rdaconclusion although tendency lower risk disease reactivation older patients incidence rda even rebound negligible age 50 60 years even patients previously stable ms ftypmid33838521 doi101016 jmsard2021102918,0.0
microstructural functional brain abnormalities multiple sclerosis predicted osteopontin neurofilament light mult scler relat disord 2021 mar 24 51102923 doi 101016 jmsard2021102923 online ahead printabstractbackground osteopontin opn proinflammatory biomarker neurofilament light chain nfl levels reflect axonal damage restingstate functional mri rsfmri defines brain networks wakeful restobjective examine levels opn nfl associated long term lesion evolution ii changes normalappearing white matter nawm microstructure iii functional connectivity multiple sclerosis ms methods concentration nfl opn blood csf related mri findings 103 28 years later 53 patients ms nfl examined simoa method opn elisa lesion volume brain cervical spinal cord examined 3d flair images voxelwise images fractional anisotropy fa axial diffusivity ad mean diffusivity md radial diffusivity rd examined tractbased spatial statistics corrected gender age lesion volume metabolites examined singlevoxel mrspectroscopy nawm fiftyfive default mode network connections examined rsfmri corrected gender age ms subtype current therapy covariatesresults nfl paired serum csf positively correlated p 0019 correlation serum csf opn higher opn levels csf serum showed association increased brain wm lesion volume p 0009 103 28 years higher opn csf associated reduced fa increased md reduced rd different nawm areas 103 28 years later higher opn serum csf associated increased connectivity strength medial prefrontal cortex mpfc regions except inferior parietal lobule nfl csf serum associated decreased connectivity strength except ventral mpfchippocampal formation neither serum opn nfl time mri associated functional connectivity changesconclusion serum nfl levels reflects cns production opn serum csf may different cellular sources opn within csf serum may forecast development lesions microstructural abnormalities 10 years indicating detrimental role cns inflammation longterm although opn nfl csf associated functional connectivity changes 10 years nfl associated decreased strength possibly indicating general axonal loss contrast positive association opn levels csf increased connectivity strength 10 years may point adaptive reorganization due inflammatory wm lesions microstructural changespmid33813096 doi101016 jmsard2021102923,0.0
use geographical information systems multiple sclerosis research systematic scoping review mult scler relat disord 2021 mar 18 51102909 doi 101016 jmsard2021102909 online ahead printabstractintroduction geographical information system gis spatial analysis emerging role understanding management healthrelated outcomes however knowledge gap extent gis supported multiple sclerosis ms research therefore review aimed explore types gis applications complexity visualisation ms researchmethods systematic scoping review conducted based yorks fivestage framework pubmed scopus web science searched relevant studies published 2000 2020 using comprehensive search strategy based main concepts related gis ms grounded inductive analysis conducted organize studies meaningful application areas developed tool assess visualisation complexity selected papersresults 3 723 identified unique citations 42 papers met inclusion criteria final review one following types gis applications reported studies thematic mapping 37 papers b spatial cluster detection 16 papers c risk factors detection 16 papers d health access planning two papers majority studies 88 score visualisation complexity relatively low three less range zero sixconclusions although number studies using gis techniques dramatically increased last decade use gis areas ms access planning still underresearched additionally capacity gis visualising complex nature ms care system yet fully investigatedpmid33813094 doi101016 jmsard2021102909,0.0
kinetic assessment michael addition reactions alpha betaunsaturated carbonyl compounds amino acid protein thiols free radic biol med 2021 apr 2s08915849 21 002008 doi 101016 jfreeradbiomed202103040 online ahead printabstracthumans extensive adverse exposure alpha betaunsaturated carbonyl compounds abucs major toxins smoke exhaust fumes well products lipid peroxidation contrast another abuc dimethylfumarate used treat psoriasis multiple sclerosis abucs undergo michael adduction amine imidazole thiol groups reaction cys residues predominating report rate constants k2 abucs acrolein crotonaldehyde dimethylfumarate cyclohex1en2one cyclopent1en2one cys residues present naccys gsh bovine serum albumin creatine kinase papain glyceraldehyde3phosphatedehydrogenase wildtype c151s mutant keap1 k2 values naccys gsh vary 250fold indicating marked abuc structure dependence acrolein reactive also considerable variation k2 protein cys groups significantly greater gsh linear inverse correlation acrolein thiol pka indicates thiolate anion reactive species modest k2 gsh rationalizes detection protein adducts abucs cells k2 values dimethylfumarate also vary markedly cys151 residue keap1 particularly reactive c151s mutant giving much lower k2 value data crotonaldehyde dimethylfumarate cyclohex1en2one show little correlation cys pka values indicating steric electronic interactions rather cys ionization important data indicate protein cys residues particularly cys151 keap1 react readily dimethylfumarate may help rationalize use compound therapeutic agentpmid33819622 doi101016 jfreeradbiomed202103040,0.0
socioeconomic consequences multiple sclerosisa systematic literature review acta neurol scand 2021 mar 22 doi 101111 ane13411 online ahead printabstractmultiple sclerosis ms challenging disabling condition predominantly affecting individuals early life impact functionally financially quality life however lack systematic approach towards assessing socioeconomic consequences ms objective systematically review observational analytical studies investigating socioeconomic consequences ms conducted systematic review socioeconomic consequences ms focus employment income work ability relationshiprelated outcomes ms general population additionally educational characteristics extracted 4958 studies identified 187 assessed eligibility total 27 studies eight countries included qualitative assessment 32 different outcomes identified studies indicated pronounced differences ms patients general population example 1530 lower employment lower earnings higher social benefits higher absenteeism presenteeism proportions higher work disability eg sickleave days among ms patients studies also indicated differences family relationship characteristics apparent differences regard educational level conclusion socioeconomic data can serve robust outcome measures study various aspects ms reflecting broader consequences diseasepmid33748960 doi101111 ane13411,0.0
characterizing patient assistance program use patient responsiveness specialty drug price multiple sclerosis midsize integrated health system j manag care spec pharm 2021 jun 27 6 732742 doi 1018553 jmcp2021276732abstractbackground concern increasingly common use patient assistance programs paps outofpocket assistance provided manufacturers foundations distorts understanding patient behavior insurance design incentives yet current literature prescription drug cost sharing largely overlooks use paps prevalence impact drug demand price elasticity major knowledge gap objective examine use paps among patients multiple sclerosis ms association drug demand specialty pharmacy program within regional integrated health system facilitates use methods used pharmaceutical claims data december 2017 december 2018 linked detailed payer information kaiser permanente washington characterize prevalence paps users 7 ms specialty drug molecules estimated price elasticity demand ped twopart model using presence copayment assistance source cost variation first part estimated marginal probability claim given month probit model comparing pap users nonusers whereas second part estimated days supplied medication given claim made measure demand results 789 unique patients 480 607 used paps least 1 drug claim 13month time frame 248 patients 314 used paps ms drug claims used copay assistance covered 100 outofpocket oop charges 98 claims reduced patient annual oop cost 3 493 average people used paps much higher oop charges lower charlson comorbidity score likely insurance exchange oop costs charged patients higher claims patient assistance used claims assistance used 294 vs 42 p 0001 total claim amount higher claims used assistance 6 169 claims 5 503 p 0001 probability patient drug claim given month 19 higher among using patient assistance although finding significant p 0258 average change price 16821 pap use led average change demand 005 days overall price elasticity demand sd 0028 p 0852 given pap use 0005 indicating presence paps significantly affect demand ped estimates statistically significant drug exclusion medicare patients change interpretation conclusions midsize integrated health system state washington program promotes adherence specialty drugs via facilitated pap use found reduce patient oop costs effect prescription drug utilization payers may consider embracing paps remove patient financial barriers necessary medications use tools cost sharing influence patient consumption specialty drugs disclosures manuscript funded part predoctoral fellowship health outcomes phrma foundation awarded brouwer completion dissertation work yeung receives salary support kaiser permanente authors nothing disclosepmid34057391 doi1018553 jmcp2021276732,0.0
low dose naltrexone conjunction wahls protocol reduce frequency chronic migraines patient multiple sclerosis case study integr med encinitas 2021 jun 20 3 3034abstractthis case study investigates efficacy low dose naltrexone ldn wahls protocol reducing frequency severity chronic migraine headaches 62yearold white female multiple sclerosis migraines common among many debilitating symptoms multiple sclerosis therapeutic intervention low dose naltrexone titrated 45 mg nightly combination dietary changes significantly improved patients quality life reducing severity duration frequency chronic migraine headachespmid34377098 pmcpmc8325503,0.0
therapeutic prospects cannabinoids immunomodulation prevalent autoimmune diseases cannabis cannabinoid res 2021 may 24 doi 101089 can20200183 online ahead printabstractintroduction cannabinoids 9thc cbd can downregulate immune response modulating endocannabinoid system modulation relevant treatment prevalent autoimmune diseases ads multiple sclerosis ms systemic lupus erythematosus sle diabetes mellitus type 1 dmt1 rheumatoid arthritis ra conditions require new therapeutic options fewer side effects control autoimmune response objective conduct literature review preclinical scientific evidence supports clinical investigations use cannabinoids natural synthetic potential immunomodulators immune response ads methodology systematic search carried different databases using different mesh terms cannabis sativa l cannabinoids immunomodulation ads initially 677 journal articles found filtering publication date 2000 2020 sle dmt1 ra 2010 2020 ms removing duplicate items 200 articles selected analyzed title summary associated use cannabinoids immunomodulatory treatment diseases results evidence immunomodulatory effect cannabinoids diseases previously mentioned sle meet search criteria summarized 24 journal articles cbd found one main modulators immune response molecule decreased number th1 th17 proinflammatory cells production proinflammatory cytokines interleukin il 1 il12 il17 interferon ifn tumor necrosis factor alpha mouse models ms dmt1 additionally new synthetic cannabinoidlike molecules agonist antagonist activity cb1 cb2 trpv1 ppar ppar receptors shown antiinflammatory properties ms dmt1 ra conclusion data experimental animal models ad showed natural synthetic cannabinoids downregulate inflammatory responses mediated immune cells responsible ad chronicity progression although synthetic cannabinoidlike molecules evaluated just two clinical trials corroborated potential use cannabinoids treat ads notwithstanding new cannabinoidbased approaches required provide alternative treatments patients affected large group adspmid34030476 doi101089 can20200183,0.0
middleage people multiple sclerosis demonstrate similar mobility characteristics neurotypical older adults mult scler relat disord 2021 mar 25 51102924 doi 101016 jmsard2021102924 online ahead printabstractbackground clinical trials often report significant mobility differences neurotypical atypical groups however analyses often determine measures capable discriminating groups additionally indirect evidence supports notion mobility impaired populations demonstrate similar mobility deficits thus current study aimed provide comprehensive analysis three distinct aspects mobility walking turning balance determine variables significantly different also able discriminate neurotypical older adults oa middleaged people multiple sclerosis pwms middleaged neurotypical adults pwmsmethods study recruited 21 neurotypical oa 19 middleaged neurotypical adults 30 people relapsing remitting ms participants came laboratory two separate occasions complete mobility testing wearing wireless inertial sensors testing included selfselected pace twominute walk series 180 360 turns clinical balance test capturing total 99 distinct mobility characteristics determined significant differences gait turning measures univariate analyses series repeated measures analysis variance determining significance balance conditions measures determining discrimination groups area curve auc calculated individual mobility measures threshold 080 denoting excellent discrimination additionally stepwise regression top five auc producing variables performed determine whether combination variables enhance discrimination accounting multicollinearityresults results neurotypical oa middleaged pwms demonstrated significant differences three gait one turning variable variable combination variables able provide excellent discrimination groups middleage neurotypical adults pwms variety mean variability gait measures demonstrated significant differences groups however variable combination variables met discriminatory threshold turning five 360 turn variables demonstrated significant differences furthermore combination 360 mean turn duration variability peak turn velocity able discriminate groups finally majority postural sway measures demonstrated significant group differences ability discriminate groups particularly challenging balance conditions participants stood compliant surfaceconclusion results offer comprehensive analysis mobility differences measures capable discriminating middleage neurotypical adults pwms additionally results provide evidence oa middleage pwms display similar movement characteristics thus potential indicator advanced aging mobility perspectivepmid33813095 doi101016 jmsard2021102924,0.0
complete evaluation dementia pet mri correlation diagnosis neuroradiologist ajnr j neuroradiol 2021 apr 29 doi 103174 ajnra7079 online ahead printabstractthis article will familiarize neuroradiologists pathophysiology clinical findings standard mr imaging pet imaging features multiple forms dementia well new emerging techniques cases compiled multiple institutions goal improved diagnostic accuracy improved patient care well information biomarkers horizon dementia topics addressed include following alzheimer disease frontotemporal dementia cerebral amyloid angiopathy lewy body dementia parkinson disease parkinson disease variants amyotrophic lateral sclerosis multisystem atrophy huntington disease vascular dementia creutzfeldtjakob diseasepmid33926896 doi103174 ajnra7079,0.0
comparative effectiveness psychotherapy approaches death anxiety multiple sclerosis patients pilot randomized controlled trial mult scler relat disord 2021 mar 19 51102914 doi 101016 jmsard2021102914 online ahead printabstractbackground death anxiety da chronic diseases occupied human mind diseases therefore multiple sclerosis ms patients prone da due recurrence periodsobjective among psychological interventions two approaches logotherapy lt acceptance commitment therapy act pay attention concentration subject suffering therefore present study aimed compare effectiveness two approaches da ms patientsmethods statistical population included 48 women diagnosed ms patients medical records iran ms society tehran terms entry exit criteria selected convenience sampling randomly divided two experimental groups one control group plan independent variable three levels including lt act control group dependent variables subjects scores death attitude profilerevised dapr wong reker gesser 1994 therapeutic interventions included 12 sessions 2 h per week 3hour workshop held control group patients provided basic information psychological problems ms strategy presented order obtain results analysis covariance used followup study repeated measures analysis variance intergroup variable mixed model usedresults showed lt act groups able effective reduce da comparison control group positive effect improvement da evident posttest followup stages however significant differences observed comparing effectiveness two intervention methods methods effective reducing da due nature sufferingconclusion considering effectiveness lt act reducing da ms patients results study can used order achieve therapeutic goals reduce psychological problems chronic diseasespmid33780806 doi101016 jmsard2021102914,0.0
guggulsterone ameliorates ethidium bromideinduced experimental model multiple sclerosis via restoration behavioral molecular neurochemical morphological alterations rat brain metab brain dis 2021 feb 26 doi 101007 s1101102100691x online ahead printabstractmultiple sclerosis ms progressive neurodegenerative disease clinical signs neuroinflammation central nervous systems demyelination numerous studies identified role janus kinase jak signal transducer activator transcription stat overexpression low level peroxisome proliferatoractivated receptorgamma ppar ms pathogenesis guggulsterone gst active component derived commiphora mukul used treat various diseases traditional uses indicate gst suitable agent antiinflammatory action therefore assessed therapeutic potential gst 30 60 mg kg ethidium bromide eb induced demyelination experimental rats investigated molecular mechanism modulating jak stat ppar receptor signaling wistar rats randomly divided six groups n 6 eb 01 10 l injected selectively intracerebropeduncle icp region seven days cause mslike manifestations present study reveals longterm administration gst 28 days neuroprotective effect improving behavioral deficits spatial cognition memory grip motor coordination associated lower stat3 levels elevating ppar myelin basic protein levels rat brains consistent functioning signaling pathways also gst modulates neurotransmitter level increasing ach dopamine serotonin reducing glutamate moreover gst ameliorates inflammatory cytokines tnf il1 oxidative stress markers ache sod catalase mda gsh nitrite addition gst prevented apoptosis demonstrated reduction caspase3 bax simultaneously bcl2 elevation restoration gross morphology alterations also recovered longterm gst treatment therefore can concluded gst may potential alternative drug candidate msrelated motor neuron dysfunctionspmid33635478 doi101007 s1101102100691x,1.0
update treatment multiple sclerosis presse med 2021 may 22104068 doi 101016 jlpm2021104068 online ahead printabstractmultiple sclerosis ms chronic inflammatory disease central nervous system recent years many diseasemodifying therapies dmt approved ms treatment reason profound knowledge characteristics indications available compounds required tailor therapeutic strategy individual patient characteristics include mechanism action pharmacokinetic drug safety efficacy profile provided clinical trials well understanding possible side effects moreover evolving knowledge disease paving way new innovative therapeutic approaches well development new biomarkers monitor therapeutic response guide clinicians therapeutic choices review provide comprehensive overview currently approved therapies ms emerging evidencebased strategies adopt initiating monitoring eventually adapting therapeutic regimen dmtpmid34033862 doi101016 jlpm2021104068,0.0
effects low vs high frequency local vibration mildmoderate muscle spasticity ultrasonographical functional evaluation patients multiple sclerosis mult scler relat disord 2021 mar 31 51102930 doi 101016 jmsard2021102930 online ahead printabstractbackground local vibration lv physiotherapy application aims reduce spasticity study aimed compare effects 50 hz vs 100 hz lv mildmoderate spasticity functional performance muscle architecturemethods thirtythree patients randomly divided three groups 50 hz lv group 100 hz lv group control group physical therapy applied one hour day three days week total eight weeks lv applied right left medial gastrocnemius muscles five minutes clinical spasticity ankle joint position sense balance gait ultrasonographic gastrocnemius fascicle length pennation angle measurements performed treatmentresults study completed 27 patients decrease spasticity increase fascicle length found statistically significant 50 hz group p005 ankle joint position sense singleleg stance time limits stability postural sway range mediolateral direction significantly improved vibration treatment groups p005 anteroposterior limits stability postural sway showed significant improvement groups p005 50 hz group showed significant improvement walking parameters velocity step length base support values improved 100 hz group p005 exercise group showed significant improvement single support stance phase percentages gait cycle p005 according group comparisons significant difference found mediolateral limits stabillity p005 mediolateral limits stabillity scores better 50 hz group 100 hz exercise groupconclusion findings show lv substantial effect except mediolateral limits stabilityclinical trial number nct04192786pmid33836458 doi101016 jmsard2021102930,0.0
multiple sclerosis patients treated diroximel fumarate realworld setting high rates persistence adherence neurol ther 2021 apr 12 doi 101007 s40120021002427 online ahead printabstractintroduction persistence multiple sclerosis ms diseasemodifying therapy fundamental maximal treatment outcomes diroximel fumarate drf approved usa relapsing ms following oral administration drf metabolized monomethyl fumarate active metabolite dimethyl fumarate dmf drf showed clinically significant improvements gastrointestinal gi tolerability versus dmf headtohead clinical trial however realworld persistence adherence assessed evaluated persistence adherence drftreated patients realworld clinical practicemethods retrospective analysis acariahealth specialty pharmacy program included patients initiating drf 4 december 2019 3 april 2020 followed data extraction 31 august 2020 exclusion criteria included undetermined treatment status eg drf prescription transfer different pharmacy endpoints included persistence overall proportion patients remaining drf discontinuation rate due gi adverse events aes adherence proportion days covered pdc gi aes included girelated aes occurring time unknown ae without details nature event unknown ae occurred 90 days drf initiationresults overall 160 patients ms included median range patient age 51 2079 years 806 129 160 patients female 163 26 160 prior dmf treatment median range treatment duration 76 01104 months estimated proportion patients remaining persistent drf treatment 8 months 886 95 confidence interval ci 82527 overall 38 6 160 patients discontinued due gi aes mean pdc 914 95 ci 891937 dmftodrf switch subgroup 923 24 26 remained persistent drf 38 1 26 discontinued drf due gi aesconclusion realworld analysis drftreated patients showed high overall persistence low discontinuation rate due gi aes high adherence therapy aligning expectations based drf clinical trials data consistent dmftodrf subgroup infographicpmid33846959 doi101007 s40120021002427,0.0
stressful life events risk primary progressive multiple sclerosis populationbased casecontrol study mult scler relat disord 2021 apr 7 51102937 doi 101016 jmsard2021102937 online ahead printabstractbackground onset presentation primary progressive multiple sclerosis ppms like autoimmune diseases can triggered unexpected lifetime stressful events require assessed order minimize exposure events much possibleobjective aim present study determine possible role socioeconomic status ses stressful events ppms development methods present populationbased casecontrol study recruited ppms cases healthy controls general population 20192020 tehran iran clinical diagnosis cases based 2017 mcdonald criteria confirmed neurologist selection sexmatched controls source population cases performed using standard method random digit dialing rdd study questionnaire filled telephone interviews matched logistic regression administered estimate adjusted unadjusted odds ratio 95 confidence intervals cis adjusted sex age marital status using spss 23results study examined 146 ppms cases 294 controls mean ages sd cases controls 4697 94 3767 612 respectively p 0001 stressful events five years prior disease onset associated increased risk ppms marriage 004 95 ci 001 037 p 0004 close family members serious disease 010 95 ci 002060 p 001 debt 003 95 ci 0037 p 0006 found negative association risk disease occurrence death loved one family disruption jail term homelessness period conquer national university entrance exam death spouse getting fired job joblessness divorce migration close family members suicide retirement associated risk ppms p 005 history depression ppms presentation considerably associated incidence ppms p 0001 selfrated health status scored noticeably lower cases compared controls p 0001 participants paternal educational degree guidance school showed higher risk ppms 283 time 283 95 ci 102 780 p 004 participants university educated fathers total ses adolescence indicate association risk ppms exception levels 2 p 002 7 p 005 conclusion stressful life events identified possible increasing risk factors ppms marriage close family members serious disease debt negative association disease risk history depression may elevate risk ppms highest lowest ses levels adolescence remarkable determiners ppms levels 2 7 positive association risk ppms maternal educational level important factor however paternal educational degree guidance school compared university degree made individuals susceptible ppms selfrated health status score higher controlspmid33857898 doi101016 jmsard2021102937,0.0
managing multiple sclerosis covid19 era review literature consensus report panel experts saudi arabia mult scler relat disord 2021 mar 25 51102925 doi 101016 jmsard2021102925 online ahead printabstractdiseasemodifying therapies dmt relapsingremitting ms rrms act immune system suggesting need caution sarscov2 covid19 pandemic group experts ms care saudi arabia convened consider impact covid19 ms care country develop consensus recommendations current application dmt therapy covid19 led disruption care ms saudi arabia elsewhere expert panel considered dmts overall tolerability safety profile important consideration whether prescribe time treatment can started continued interferon beta teriflunomide dimethyl fumarate natalizumab dmts associated increased risk infection consensus initiation dmts consensus also supported continuing treatment regimens fingolimod siponimod cladribine tablets patient without active covid19 dmt imitated patient active covid19 interferon beta continued case covid19 infection vaccination covid19 therapeutic priority people ms new treatment delayed 24 weeks vaccination treatment already ongoing vaccination covid19 administered immediately without disruption treatment firstline dmts natalizumab fingolimod lymphocytes recovered sufficiently cladribine tablets alemtuzumab 4 months last dose ocrelizumab recommendations will need refined updated new clinical evidence area emergespmid33857897 doi101016 jmsard2021102925,0.0
movement compensations step ascent task associated stair climbing performance people multiple sclerosis gait posture 2021 apr 15 872732 doi 101016 jgaitpost202104022 online ahead printabstractbackground biomechanical mechanisms underlying stair climbing limitations poorly understood people multiple sclerosis ms research questions trunk pelvis motion lower extremity joint moments step ascent different ms control groups step ascent biomechanics stair climbing performance associated people msmethods 20 people ms 49 12 years edss range 1555 ten control participants 48 12 years underwent threedimensional motion analysis ascending 152cm step also completed timed functional stair test main effects group ms vs control limb stronger dominant vs weaker nondominant interactions assessed using twoway analyses variance associations movement patterns step ascent functional stair test performance performed using pearsons correlations backward stepwise linear regressionresults significant group main effects observed greater sagittal pelvis excursion p 0001 greater sagittal p 0013 frontal p 0001 trunk excursion lower trail limb peak ankle plantar flexion moment p 0001 ms group significant limb main effects observed greater sagittal trunk excursion p 0037 peak trail limb ankle plantar flexion moment p 0037 stronger dominant limb significant interaction observed peak knee extensor moment p 002 stair climbing performance ms group correlated sagittal r 607 p0001 frontal pelvis excursions r 0385 p 0014 sagittal trunk excursion r 411 p 0008 ankle plantar flexion moments r0415 p 0008 sagittal frontal pelvis excursion bilateral handrail use explained significant amount variability stair climbing performance adj r2 0775 significance conclusion despite presence proximal distal lower extremity movement pattern compensations step ascent task larger pelvis angular excursions associated impaired stair climbing performance people ms may serve targets future rehabilitation interventionspmid33878510 doi101016 jgaitpost202104022,0.0
case idiopathic portal hypertension accompanying multiple hepatic nodular regenerative hyperplasia patient systemic sclerosis clin j gastroenterol 2021 apr 22 doi 101007 s1232802101348z online ahead printabstractidiopathic portal hypertension iph one background diseases causing nodular regenerative hyperplasia nrh furthermore iph patients accompanied autoimmune diseases systemic lupus erythematosus sle systemic sclerosis ssc likely form nrh liver 76yearold woman aware raynauds phenomenon scleroderma past 30 years case presented abdominal fullness imaging analysis revealed ascites multiple liver nodules gdeobdtpa enhanced magnetic resonance imaging eobmri donutlike uptake observed nodules hepatobiliary phase liver biopsy nodule demonstrated composed hyperplastic hepatocytes without fibrous septa dilated sinusoids observed beside nodule conversely background liver showed peripheral portal veins appeared stenotic dense fibrosis portal area final diagnosis multiple nrh liver developed ssc patient accompanying iph case suggests nrh may unexpectedly diagnosed patients autoimmune diseases accompanying iphpmid33886104 doi101007 s1232802101348z,0.0
three distinct tolerogenic cd14+ myeloid cell types actively manage autoimmune disease opportunities challenges j autoimmun 2021 apr 23 120102645 doi 101016 jjaut2021102645 online ahead printabstractcurrent treatment patients autoimmune disorders including rheumatoid arthritis multiple sclerosis type 1 diabetes often consists longterm drug regimens broadly dampen immune responses nonspecific treatments frequently associated severe side effects creating urgent need safer effective therapy promote peripheral tolerance autoimmune diseases cellbased immunotherapy may offer encouraging alternative tolerogenic cd14+ myeloid cells infused inhibit autoreactive effector cells review compared depth three promising tolerogenic cd14+ candidates treatment autoimmune disease 1 tolerogenic dendritic cells 2 monocytic myeloidderived suppressor cells 3 cd14+ type 2 conventional dendritic cells toldcbased therapy entered clinical testing whereas evidence latter two cell types mmdscs cd14+ cdc2s predominantly coming cancer immunology research three cell types distinct cellular properties immunosuppressive mechanisms offering unique opportunities explored however cells differ stage development towards immunotherapy facing additional hurdles therefore speculate potential benefits risks cell types novel cellbased immunotherapies control autoimmune disease patientspmid33901801 doi101016 jjaut2021102645,0.0
potential pitfalls preimplantation genetic diagnosis patient tuberous sclerosis isolated mosaicism tsc2 variant renal tissue mol syndromol 2021 jun 12 3 154158 doi 101159 000513326 epub 2021 mar 9abstracttuberous sclerosis complex tsc autosomal dominant disorder displays wide spectrum clinical manifestations often affecting multiple organs including kidneys brain lungs skin pathogenic mutation either tsc1 tsc2 gene can detected almost 85 cases mosaicism accounting half remaining cases report case tsc diagnosed clinically requesting genetic counselling regarding reproductive risks mutation identified initial testing peripheral blood however mosaicism likely pathogenic frameshift variant tsc2 detected level 15 renal angiomyolipoma tissue despite widespread clinical manifestations tcs variant detected skin fibroblasts saliva raising possibility isolated somatic mutation renal tissue underlying germline mutation yet identified case highlights difficulties counselling patients mosaicism regarding reproductive risks prenatal diagnostic optionspmid34177431 pmcpmc8215990 doi101159 000513326,0.0
many roles oligodendrocyte precursor cells physiology pathology neuropathology 2021 apr 28 doi 101111 neup12732 online ahead printabstractoligodendrocyte precursor cells opcs fourth resident glial cell population mammalian central nervous system evenly distributed throughout gray white matter continue proliferate generate new oligodendrocytes ols throughout life understudied decades ago immunolabeling ng2 plateletderived growth factor receptor alpha revealed cells distinct mature ols astrocytes neurons microglia review provide summary known properties opcs historical background followed highlights recent studies suggest new roles opcs certain pathological conditionspmid33913208 doi101111 neup12732,0.0
corrigendum quot low back pain patients multiple sclerosis systematic review prevalence french multiple sclerosis populationquot revue neurologique volume 177 issue 4 april 2021 pages 349358 rev neurol paris 2021 apr 28s00353787 21 005105 doi 101016 jneurol202104002 online ahead printno abstractpmid33933292 doi101016 jneurol202104002,0.0
comprehensive approach management multiple sclerosis addressing invisible symptomsa narrative review neurol ther 2021 apr 20 doi 101007 s40120021002392 online ahead printabstractmultiple sclerosis ms chronic autoimmune inflammatory disease central nervous system leading neurodegeneration manifesting variety symptoms can include invisible symptoms externally evident others fatigue mood disorders cognitive impairments pain bladder bowel dysfunction sexual dysfunction vision changes invisible symptoms highly prevalent people living ms multifactorial etiology potential impact disease course patient experiences symptoms include physical psychosocial elements unaddressed negatively influence many aspects quality life perception health despite high impact patient lives gaps persist awareness management hidden symptoms healthcare provider patient author experiences brought together serve raise profile invisible symptoms review strategies teambased approach comprehensive ms care summarize current literature regarding prevalence etiology invisible symptoms convey high likelihood person living ms will contend one concerns explore open communication people living ms care team stigma mitigation shared decisionmaking key comprehensive management invisible symptoms recommend validated screening tools technological advancements may incorporated ms care regularly monitor symptoms offering insight healthcare providers can educate listen patients goal improved patient quality life pairing clinical knowledge understanding consideration patient perspective providers will equipped foster patientcentered dialogue encourages shared decisionmaking invisible symptoms mspmid33877583 doi101007 s40120021002392,0.0
pilot randomized controlled trial robotic exoskeletonassisted exercise rehabilitation multiple sclerosis mult scler relat disord 2021 apr 13 51102936 doi 101016 jmsard2021102936 online ahead printabstractbackground cooccurring mobility cognitive impairments common debilitating poorlymanaged pharmacological therapies persons multiple sclerosis ms exercise rehabilitation er particularly walking er suggested one best approaches managing manifestations ms however focal lack efficacy er mobility cognitive outcomes persons ms present substantial neurological disability severe neurological disability oftentimes precludes ability participation highlyintensive repetitive er necessary eliciting adaptations mobility cognition address concern robotic exoskeletonassisted er reaer might represent promising intervention approach managing cooccurring mobility cognitive impairments substantial ms disability might benefit traditional ermethods current pilot singleblind randomized controlled trial rct compared effects 4weeks reaer 4weeks conventional gait training cgt standardofcare control condition functional mobility timed upandgo tug walking endurance sixminute walk test 6mwt cognitive processing speed cps symbol digit modalities test sdmt brain connectivity thalamocortical restingstate functional connectivity rsfc based fmri outcomes 10 persons substantial msrelated neurological disabilityresults overall compared cgt 4weeks reaer associated large improvements functional mobility p238 cps p253 rsfc thalamus ventromedial prefrontal cortex p272 walking endurance p201 changes rsfc moderately associated changes tug 6mwt sdmt performance respectively whereby increased thalamocortical rsfc associated improved functional mobility walking endurance cps 36 conclusion current pilot rct provides initial support reaer approach improving functional mobility cps perhaps based adaptive integrative central nervous system plasticity namely increases rsfc thalamus ventromedial prefrontal cortex small sample persons substantial ms disability pilot trial provides proofofconcept data design implementation appropriatelypowered rct reaer larger sample persons ms present cooccurring impairments mobility cognitive functioningpmid33878619 doi101016 jmsard2021102936,0.0
validation finnish version brief international cognitive assessment multiple sclerosis bicams evaluation applicability multiple sclerosis neuropsychological questionnaire msnq fatigue scale motor cognitive functions fsmc brain behav 2021 may 7e02087 doi 101002 brb32087 online ahead printabstractobjectives cognitive impairment frequent multiple sclerosis ms approximately half patients manifest degree cognitive impairment brief international cognitive assessment multiple sclerosis bicams designed brief cognitive evaluation purpose study validate bicams along finnish versions one selfrating questionnaire cognition fatiguemethods total 65 ms patients 45 healthy controls hc assessed bicams multiple sclerosis neuropsychological questionnaire msnq fatigue scale motor cognitive functions fsmc twice approximately within nine daysresults ms patients scored markedly lower hcs three tests bicams patients 60 scored least 15 sd mean hcs least one test 49 sdmt 26 cvltii 28 bvmtr correlation coefficients repeated measurement 075 089 three tests whole study sample ms patients reported cognitive symptoms fatigue hcs cronbachs alpha 094 msnq 098 fsmc correlation coefficient repeated measurement 091 msnq 092 094 fsmc scores whole study sampleconclusions present study supports validity finnish version bicams sdmt sensitive three bicams tests showed cognitive impairment half patients finnish versions msnq fsmc proved useful tools approaching concerns related cognition fatiguepmid33960700 doi101002 brb32087,0.0
racial differences response multiple sclerosis therapy nat rev neurol 2021 may 7 doi 101038 s41582021005077 online ahead printno abstractpmid33963307 doi101038 s41582021005077,0.0
trichinella spiralis excretorysecretory products downregulate mmp9 dark agouti rats affected experimental autoimmune encephalomyelitis exp parasitol 2021 may 5108112 doi 101016 jexppara2021108112 online ahead printabstractmatrix metalloproteinases mmps implicated pathogenesis multiple sclerosis ms animal model experimental autoimmune encephalomyelitis eae aim investigate whether amelioration eae dark agouti da rats induced trichinella spiralis muscle larvae excretorysecretory products es l1 related level activity gelatinases mmp9 mmp2 serum levels mmp9 mmp2 ngal mmp9 timp1 cytokines evaluated gelzymography elisa well gelatinases timp1 expression spinal cord sc determined eae induced ii es l1treated eae induced animals milder clinical signs es l1treated eae induced da rats accompanied lower serum levels mmp9 ngal mmp9 complex however correlation severity eae level serum mmp9 found peak disease mmp9 timp1 ratio higher eae animals without es l1 treatment lower expression mmp9 sc es l1treated eae induced rats correlated reduced number sc infiltrating cells sc infiltrates effector recovery phase production antiinflammatory cytokines il4 il10 higher animals treated es l1 prior eae induction compared untreated eae animalsreduced expression mmp9 sc tissue correlated reduced number infiltrating cells might ascribed regulatory mechanisms among il10pmid33964315 doi101016 jexppara2021108112,0.0
identification patients relapsing multiple sclerosis eligible highefficacy therapies neurodegener dis manag 2021 may 10 doi 102217 nmt20200049 online ahead printabstractrelapsing multiple sclerosis rms presents highly variable clinical evolution among patients management personalized although cure present effective diseasemodifying therapies dmts available selection appropriate dmt patient influenced several clinical radiological demographic aspects well personal preferences times covered regulatory criteria may source difficulty especially certain situations socalled highefficacy dmts usually considered secondline greater benefit patient narrative review discuss evidence experience propose pragmatic guidance decisionmaking respect indication management highefficacy dmt adult patients rms based expert opinionpmid33966475 doi102217 nmt20200049,0.0
protective variant autophagy receptor calcoco2 ndp52 multiple sclerosis ms autophagy 2021 may 1013 doi 101080 1554862720211924969 online ahead printabstractmultiple sclerosis ms autoimmune disease central nervous system found associated dysfunctional mitochondria order advance understanding complex molecular mechanisms underlying disease analyzed mitophagy process fundamental elimination damaged mitochondria autophagic process peripheral blood mononuclear cells pbmcs ms patients genetic analysis carried 203 ms patients 1000 healthy controls identified natural variant calcoco2 ndp52 wellknown autophagic receptor associated protective ms structural modeling calcoco2 variant functional studies highlighted amino acid substitution g140e located near lc3interacting region lir motif calcoco2 crucial controlling mitophagy addition found among pbmcs calcoco2 mainly expressed b cells mediating mitophagy reduces proinflammatory cytokine production following stimulation cells summarize recent findings discuss putative protective roles calcoco2 b cells novel association autoimmune disease mspmid33970776 doi101080 1554862720211924969,0.0
whole exome sequencing provides correct diagnosis case osteopathia striata cranial sclerosis case report novel frameshift mutation amer1 j pediatr genet 2021 jun 10 2 139146 doi 101055 s00401710058 epub 2020 apr 21abstractthe diagnosis rare diseases multisystem manifestations can constitute difficult process delays determination underlying cause whole exome sequencing wes provides suitable option examine multiple target genes associated several disorders display common features study report case female patient suspected sotos syndrome screening initially selected genes considering sotos syndrome sotoslike disorders identify pathogenic variants explain phenotype extended analysis considered genes exome associated features consistent shown studied patient revealed novel frameshift variant amer1 gene responsible osteopathia striata cranial sclerosis wes analysis updated revision previously reported diseasecausing mutations proved useful reach accurate diagnosis guide examination identify critical abnormalitiespmid33996185 pmcpmc8110338 doi101055 s00401710058,0.0
evaluation optical coherence tomography angiography findings patients multiple sclerosis indian j ophthalmol 2021 jun 69 6 14571463 doi 104103 ijoijo_2964_20abstractpurpose evaluate optical coherence tomography angiography findings patients multiple sclerosis ms methods prospective noninterventional study conducted 30 eyes relapsingremitting ms patients group 1 included 10 eyes history optic neuritis group 2 included 10 eyes without history optic neuritis mson group 3 included 10 eyes normal age sex refraction matched participants optical coherence tomography oct octa zeiss cirrus hdoct model 4000 carl zeissmeditec dublin ca optic disc done patientsresults bestcorrected visual acuity diminished ms cases especially patients p value 0001 retinal nerve fiber layer rnfl thickness showed significant decrease average thickness quadrants notably temporal quadrant group 1 p 0001 ganglion cell layer thickness diminished average thickness quadrants groups ms first group showed statistical significance p value 0001 respect optic disc perfusion average superficial deep vascular density index avdi vdi 1 vdi 2 statistically significantly lower groups 1 2 pvalue 0001 conclusion decreased vascular perfusion optic nerve ms patients especially strongly correlated damage rnfl ganglion cell layer detected octpmid34011720 doi104103 ijoijo_2964_20,0.0
riboflavin neurological diseases narrative review clin drug investig 2021 apr 22 doi 101007 s40261021010381 online ahead printabstractriboflavin classified one watersoluble b vitamins part functional group flavin mononucleotide fmn flavin adenine dinucleotide fad cofactors required numerous flavoproteincatalysed reactions riboflavin important antioxidant properties essential correct cell functioning required conversion oxidised glutathione reduced form mitochondrial respiratory chain complexes ii contain flavoprotein reductases electron transferring flavoproteins riboflavin deficiency demonstrated impair oxidative state body especially relation lipid peroxidation status animal human studies nervous system riboflavin essential synthesis myelin deficiency can determine disruption myelin lamellae inherited condition restricted riboflavin absorption utilisation reported 1015 world population warrants investigation relation association main neurodegenerative diseases several successful trials testing riboflavin migraine prevention performed drug currently classified level b medication migraine according american academy neurology evidencebased rating evidence supporting efficacy brownvialettovan laere syndrome faziolonde diseases now renamed riboflavin transporter deficiency autosomal recessive diseases caused mutations slc52a2 slc52a3 genes encode riboflavin transporters high doses riboflavin represent mainstay therapy diseases high doses riboflavin rapidly started soon diagnosis suspected continued lifelong remarkably mitochondrial diseases respond supplementation riboflavin include multiple acylcoadehydrogenase deficiency caused etfdh gene mutations majority cases mutations etfa etfb genes minority mutations acad9 gene mutations aifm1 gene mutations ndufv1 ndufv2 genes therapeutic riboflavin administration tried neurological diseases including stroke multiple sclerosis friedreichs ataxia parkinsons disease unfortunately design clinical trials uniform allowing accurately assess real effects molecule disease course review analyse properties riboflavin possible effects pathogenesis different neurological diseases will review current indications vitamin therapeutic intervention neurologypmid33886098 doi101007 s40261021010381,1.0
multiple sclerosis diagnostic criteria poser 2017 revised mcdonald criteria presse med 2021 oct 27104089 doi 101016 jlpm2021104089 online ahead printno abstractpmid34718114 doi101016 jlpm2021104089,0.0
diroximel fumarate relapsing forms multiple sclerosis profile use cns drugs 2021 may 31 doi 101007 s4026302100830z online ahead printabstractdiroximel fumarate vumerity orally administered diseasemodifying drug dmd expands available treatment options adults relapsing forms multiple sclerosis ms including clinically isolated syndrome relapsingremitting ms rrms active secondary progressive ms demonstrates bioequivalence dimethyl fumarate developed provide similar clinical benefits improved gastrointestinal gi tolerability profile rrms patients treatmentnave previously treated interferon glatiramer acetate diroximel fumarate reduces annualized relapse rates patients experiencing relapses treatment reduces formation new msassociated brain lesions diroximel fumarate acceptable tolerability profile consistent dimethyl fumarate albeit significantly lower rate gi adverse eventspmid34057708 doi101007 s4026302100830z,0.0
failed interrupted inconclusive trials neuroprotective neuroregenerative treatment strategies multiple sclerosis update 20152020 drugs 2021 jun 4 doi 101007 s4026502101526w online ahead printabstractin recent past plethora drugs approved treatment multiple sclerosis ms therapeutics mainly confined immunomodulatory immunosuppressive strategies sufficiently address remyelination neuroprotection however several neuroregenerative agents shown potential preclinical research entered phase iii clinical trials although none compounds yet proceeded approval understanding causes failure can broaden knowledge neuroprotection neuroregeneration ms moreover investigated approaches characterised consistent mechanisms action proved convincing efficacy animal studies therefore learning failure will help us enforce translation findings acquired preclinical studies clinical application summarise trials ms treatment published since 2015 either failed interrupted due lack efficacy adverse events reasons outline rationale underlying drugs analyse background failure gather new insights ms pathophysiology optimise future study designs conciseness review focuses agents promoting remyelination medications primarily neuroprotective properties unconventional approaches failed clinical trials pursue immunomodulation presented separate articlepmid34086251 doi101007 s4026502101526w,1.0
candidate biomarker glial fibrillary acidic protein csf blood differentiating multiple sclerosis subtypes systematic review metaanalysis mult scler relat disord 2021 feb 25 51102870 doi 101016 jmsard2021102870 online ahead printabstractobjective multiple sclerosis ms inflammatory demyelinating autoimmune disease central nervous system glial fibrillary acidic protein gfap monomeric intermediate filament protein systematic review metaanalysis performed regarding candidate biomarker astrocytic damage cerebrospinal fluid csf blood gfap levels differentiating multiple sclerosis subtypesmethods relevant studies published prior october 2020 retrieved pubmed web science cochrane library clinicaltrialsgov databases using following keywords multiple sclerosis ms glial fibrillary acidic protein gfap two authors independently selected articles extracted data 31 full articles screened 11 included qualitative analysis metaanalysis differences mean csf blood gfap levels used main efficacy measures metaanalysis performed using review manager version 53 softwareresults eleven clinical trials comprising 960 patients selected csf gfap levels higher 503 ms patients 252 healthy disease controls moderate effect size 072 p 000001 mean csf gfap levels significantly higher 325 ms patients relapsing disease 140 ms patients progressive disease smd047 95 ci080 015 p 0005 csf gfap levels 161 ms patients relapse irrespective ms subtype significantly higher 180 ms patients remission md10383 95 ci6809 to13957 p0001 performances gfap blood differentiating patients ms controls also significant blood gfap higher 245 ms patients 53 healthy disease controls moderate effect size 3725 p 000001 conclusion level csfgfap correlated ms different subtypes reflecting different degrees damage astrocytes different subtypes ms addition progressive ms closely related increase cerebrospinal fluid gfap level relapsingremitting ms gfap may useful marker disease progression moreover gfap level blood ms patients higher control group sample size needs expanded verification futurepmid33819724 doi101016 jmsard2021102870,1.0
involvement nlrp3 inflammasome treatment neurodegenerative diseases biomed pharmacother 2021 mar 2 138111428 doi 101016 jbiopha2021111428 online ahead printabstractin ageing society neurodegenerative diseases attracted attention high incidence worldwide despite extensive research lack conclusive insights pathogenesis neurodegenerative diseases limit strategies symptomatic treatment therefore better elucidation molecular mechanisms involved neurodegenerative diseases can provide important theoretical basis discovery new effective prevention treatment methods innate immune system activated ageing process response neurodegenerative diseases inflammasomes multiprotein complexes play important role activation innate immune system mediate inflammatory reactions pyroptosis closely involved neurodegeneration different types inflammasomes although nucleotidebinding oligomerization domainlike receptor pyrin domaincontaining 3 nlrp3 inflammasome common inflammasome nlrp3 plays important role pathogenesis neurodegenerative diseases review will discuss mechanisms involved activation nlrp3 inflammasome crucial role pathology neurodegenerative disorders alzheimers disease parkinsons disease amyotrophic lateral sclerosis multiple sclerosis will also review various treatments target nlrp3 inflammasome pathway alleviate neuroinflammation finally will summarize novel treatment strategies neurodegenerative disorderspmid33667787 doi101016 jbiopha2021111428,1.0
baseline cognitive status participant specific characteristics edss impact changes cognitive performance following aerobic exercise intervention multiple sclerosis mult scler relat disord 2021 mar 18 51102905 doi 101016 jmsard2021102905 online ahead printabstractpurpose cognitive impairment common symptom multiple sclerosis ms physical exercise represents promising nonpharmacological therapy option however potential predictors successful cognitive improvements mediated exercise remain elucidated order optimize targeted exercise training regimens one promising exercise training regime context highintensity interval training hiit backdrop study analysed effects threeweek hiit compared moderate continuous exercise cognitive performance ii investigated potential predictors changes cognitive performance following threeweek aerobic exercise interventionmethods datasets two randomized controlled trials rct pooled resulting total sample size n 130 persons ms pwms either performed hiit moderate intensity continuous mct exercise 35x week three weeks cognitive performance assessed brief international cognitive assessment ms potential within time interaction time x group effects cognitive performance investigated univariate analyses covariance ancova ii potential predictors changes cognitive performance assessed multiple linear regression modelsresults ancova revealed significant time effects cognitive outcomes time x group interaction verbal learning p045 hiit inducing superior effects compared moderate continuous exercise mct cognitive status impaired intact cognition p 008 exercise regime hiit moderate continuous p040 influenced changes verbal learning cognitive status p006 edss p048 affected changes visuospatial memory pwms models accounted 54 77 varianceconclusion cognitive status exercise regime edss potentially impact changes specific cognitive domains following aerobic exercise predictors changes cognitive performance following aerobic exercise intervention need investigated current results accounted limited amount variance rcts investigate effects physical exercise cognitive performance include pwms impaired baseline cognitive performance better understand impact exercise cognitive performance furthermore recommendable include cognitive assessments clinical routinepmid33836459 doi101016 jmsard2021102905,0.0
meningeal inflammation multiple sclerosis induces phenotypic changes cortical microglia differentially associate neurodegeneration acta neuropathol 2021 mar 29 doi 101007 s00401021022934 online ahead printabstractmeningeal inflammation strongly associates demyelination neuronal loss underlying cortex progressive ms patients thereby contributing significantly clinical disability however pathological mechanisms meningeal inflammationinduced cortical pathology still largely elusive extensive analysis cortical microglia postmortem progressive ms tissue identified cortical areas two msspecific microglial populations termed ms1 ms2 cortex microglial population ms1 cortex characterized higher density increased expression activation markers hla class ii cd68 whereas microglia ms2 cortex showed increased morphological complexity loss p2y12 tmem119 expression interestingly populations associated inflammation overlying meninges timedependently replicated vivo rat model progressive mslike chronic meningeal inflammation recently developed animal model cortical microglia 1month postinduction experimental meningeal inflammation resembled microglia ms1 cortex microglia 2 months postinduction acquired ms2like phenotype furthermore observed ms1 microglia ms cortex animal model found closely apposing neuronal cell bodies mediate presynaptic displacement phagocytosis coincided relative sparing neurons contrast microglia ms2 cortex involved synaptic alterations instead associated substantial neuronal loss taken together results show response meningeal inflammation microglia acquire two distinct phenotypes differentially associate neurodegeneration progressive ms cortex furthermore vivo data suggests microglia initially protect neurons meningeal inflammationinduced cell death removing presynapses neuronal soma eventually lose protective properties contributing neuronal losspmid33779783 doi101007 s00401021022934,1.0
lung cancer risk patients multiple sclerosis mendelian randomization analysis mult scler relat disord 2021 mar 27 51102927 doi 101016 jmsard2021102927 online ahead printabstractbackground relationship multiple sclerosis ms lung cancer debate conventional observational studies reported conflicting findings studies susceptible confounding reverse causation mendelian randomization approach able evaluate causality ms lung cancermethods according published genomewide association studies gwass obtained 35 msrelated singlenucleotide polymorphisms used instrumental variables study summary data individuallevel genetic information obtained international lung cancer consortium ilcco total 15 861 controls 11 348 cases latter composed patients lung adenocarcinoma squamous cell lung cancer inverse varianceweighted method applied estimate causation ms lung cancer evaluate pleiotropy mregger weighted median methods implementedresults results mr analysis suggested causal effect ms lung cancer incidence evidence increased risk overall lung cancer odds ratio 10648 95 confidence interval ci 1016311156 p 00082 however subgroup analyses showed significant causal relationships ms lung adenocarcinoma 10716 95 ci 0984011671 p 01119 squamous cell lung cancer 10284 95 ci 0957511045 p 04424 addition pleiotropy found studyconclusion study indicated ms causal risk factor development lung cancer work needed elucidate potential mechanismspmid33812221 doi101016 jmsard2021102927,0.0
flavonoids compounds antiinflammatory immunomodulatory properties promising tools multiple sclerosis ms therapy systematic review preclinical evidence int immunopharmacol 2021 mar 23 95107562 doi 101016 jintimp2021107562 online ahead printabstractmultiple sclerosis ms experimental autoimmune encephalomyelitis eae animal model ms diseases resulting neurological disabilities regarded chronic inflammatory autoimmune diseases central nervous system cns respect use antiinflammatory compounds including flavonoids polyphenolic compounds abundantly found vegetables fruits proposed combat ms dampen inflammation thereby ameliorating disease severity objective study clarify probable therapeutic effect flavonoids treatment ms therefore english published articles reported therapeutic effect flavonoids alone combination antims therapeutic agents ms selected searching scientific electronic databases including pubmed scopus web science evaluation selected researches 686 showed total 13 studies suitable included systematic review interestingly studies 11 studies concerning eae 2 studies concerning ms reported positive outcomes therapeutic effect flavonoids eae ms flavonoid compounds mentioned herein successfully decrease maximum clinical score eae particularly connected antiinflammatory property compounds literature review clearly discloses flavonoids alone combination antims therapeutic agents can pave way improving ms therapeutic strategiespmid33770729 doi101016 jintimp2021107562,0.0
freiburg neuropathology case conference 42yearold patient progressive neurological deficits multiple brain lesions accompanying affection peripheral nerves clin neuroradiol 2021 jun 11 doi 101007 s00062021010215 online ahead printno abstractpmid34115143 doi101007 s00062021010215,0.0
electric fan use cooling hot weather biophysical modelling study lancet planet health 2021 jun 5 6 e368e377 doi 101016 s25425196 21 001364abstractbackground hot weather electric fans can potentially provide effective cooling people lower greenhouse gas emissions cost air conditioning however international public health organisations regularly discourage fan use temperatures higher 35c despite little evidence aimed determine humiditydependent temperature thresholds electric fans become detrimental different age groupsmethods used biophysical modelling determine upper humiditydependent temperature thresholds fan use become detrimental ie worsen heat stress healthy young adults aged 1840 years healthy older adults aged 65 years older adults taking anticholinergic medication also obtained hourly environmental data period jan 1 2007 dec 31 2019 108 populous cities determine number days fan use effective cooling standardised 31day hot weather month established simplified temperature thresholds future fan use recommendations basis temperatures fan use never detrimental jan 1 2007 dec 31 2019 across prevailing levels ambient humidityfindings according model fan use beneficial 300 966 31 hot weather days healthy young adults 294 949 31 hot weather days older adults older adults taking anticholinergic medication jan 1 2007 dec 31 2019 adherence current recommendation fan use temperatures 35c fan use recommended 272 days 877 31 hot weather days according simplified thresholds fan use temperatures 390c healthy young adults 380c healthy older adults 370c older adults taking anticholinergic medication fan use recommended 296 955 31 hot weather days healthy young adults 294 948 days healthy older adults 288 930 days older adults taking anticholinergic medication jan 1 2007 dec 31 2019interpretation electric fan use particularly healthy young adults worsened heat stress majority study days 2007 2019 newly proposed thresholds fan use provide simple guidelines improve future heatwave fan use recommendationsfunding nonepmid34119011 doi101016 s25425196 21 001364,0.0
combination long shortread sequencing fully resolves complex repeats herpes simplex virus 2 strain ms complete genome microb genom 2021 jun 7 6 doi 101099 mgen0000586abstractherpes simplex virus serotype 2 hsv2 ubiquitous human pathogen causes recurrent genital infections ulcerations many hsv2 strains different biological properties identified genomes hsv2 strains hg52 sd90e 333 reported complete fully characterized sequences de novo assembled annotated manually curated complete genome sequence hsv2 strain ms highly neurovirulent strain originally isolated multiple sclerosis patient resolved dna ends well complex inverted repeats regions present hsv genomes usually undisclosed previous published partial herpesvirus genomes using long reads pacific biosciences pacbio technology additionally identified isomeric genomes determining alternative relative orientation unique fragments genome sequenced viral population illumina shortread sequencing crucial examine genetic variability nucleotide polymorphisms insertion deletions sequence determinants strainspecific virulence factors used illumina data fix two disrupted open reading frames found coding homopolymers pacbio assembly results support combination long shortread sequencing technologies precise effective approach accurate de novo assembly curation complex microbial genomespmid34170814 doi101099 mgen0000586,0.0
efficacy allogeneic hematopoietic cell transplantation autoimmune diseases transplant cell ther 2021 mar 25s26666367 21 008009 doi 101016 jjtct202103023 online ahead printabstractbackground allogeneic hematopoietic cell transplantation hct may efficacious autoimmune diseases aids efficacy aid unknown factors influencing likelihood relapse aid also unknownobjective determine likelihood relapse common aid generate hypotheses factors influencing likelihood relapsemethods reviewed charts adult patients nonhematologic aids undergone hct alberta n21 patients described literature n67 used stringent inclusion criteria minimize inclusion patients whose aid may cured pretransplant also used stringent definitions aid relapse remissionresults aid relapsed 2 9 22 patients lupus 4 12 33 rheumatoid arthritis ra 0 4 0 systemic sclerosis ssc 3 16 19 psoriasis 1 12 8 behcets disease bd 1 15 7 crohns disease cd 0 5 0 ulcerative colitis uc 4 8 50 multiple sclerosis ms 3 3 100 type 1 diabetes t1dm among highly informative patients followed 1 year discontinuation immunosuppressive therapy relapse donor aid status known relapse relapse occurred 0 3 patients lupus 2 7 ra 0 2 ssc 3 6 psoriasis 0 3 bd 0 10 cd 0 3 uc 2 3 ms 2 2 t1dm appeared relation aid relapse low intensity pretransplant chemoradiotherapy multiple lines aid therapy surrogate aid refractoriness except perhaps lupus absence serotherapy graftvshost disease gvhd prophylaxis lack gvhd except perhaps lupus incomplete donor chimerismconclusions despite remission commonly occurring hct lupus ra ssc psoriasis bd cd uc hct efficacious subset patients efficacy appears unrelated pretransplant therapy gvhd chimerism large studies needed determine aid characteristics patients likely benefit hctpmid33775907 doi101016 jjtct202103023,0.0
safety s1p modulators patients immunemediated diseases systematic review metaanalysis drug saf 2021 mar 5 doi 101007 s4026402101057z online ahead printabstractintroduction sphingosine1phosphate modulators approved treatment multiple sclerosis development immunemediated conditions however safety concerns arisenobjective objective systematic review investigate safety profile s1p modulators patients multiple sclerosis ulcerative colitis crohns disease psoriasis systemic lupus erythematosusmethods searched medline embase cochrane central register controlled trials 1 january 1990 1 april 2020 also performed manual review conference databases 2017 2020 primary outcome occurrence adverse events serious adverse events also estimated occurrence serious infections herpes zoster infection malignancy bradycardia atrioventricular block macular edema performed metaanalysis controlled studies assess risks eventsresults identified 3843 citations 26 studies finally included comprising 9604 patients exposed sphingosine1phosphate modulator metaanalysis randomized controlled trials showed increased risk herpes zoster infection risk ratio 175 95 confidence interval 109280 bradycardia 264 177396 atrioventricular block 173 103291 among subjects exposed sphingosine1phosphate modulators compared placebo active comparatorconclusions found increased risk herpes zoster infection transient cardiovascular events among patients treated sphingosine1phosphate modulatorsclinical trial registration prospero crd42020172575pmid33666900 doi101007 s4026402101057z,0.0
proteinprotein interaction silico mutagenesis studies il17a peptide inhibitor 3 biotech 2021 jun 11 6 305 doi 101007 s1320502102856y epub 2021 may 31abstractproteinprotein interactions interleukin17 il17 play vital role autoimmune inflammatory diseases rheumatoid arthritis multiple sclerosis psoriasis potent therapeutics diseases developed blocking modulating interactions biologics peptide inhibitors small molecule inhibitors unlike biologics peptide inhibitors cost effective can orally available peptide inhibitors require binding groove small molecules either therefore crystal structure il17a complex high affinity peptide inhibitor hap 1ihvtipadlwdwin14 investigated aim find hot spots improve potency silico mutagenesis strategy implemented using foldx pssm scan positions tolerant amino acid substitution three positions t4 a7 n14 showed improved stability mutated f m y p f m y respectively set 31 mutant peptides designed combinations tolerant mutations using build model application foldx binding affinity interactions 31 peptides assessed proteinpeptide docking binding free energy calculations two peptides namely p1 1ihvtippdlwdwiy14 p2 1ihvmippdlwdwif14 showed better binding affinity il17a dimerization site compared hap interactions p1 p2 hap also analyzed 100 ns molecular dynamics simulations using gromacs v50 results revealed p2 peptide likely offer better potency compared hap p1 therefore p2 peptide can synthesized develop oral therapies autoimmune inflammatory diseases experimental evaluationssupplementary information online version contains supplementary material available 101007 s1320502102856ypmid34194898 pmcpmc8167077 doi101007 s1320502102856y,0.0
eculizumab asian patients antiaquaporiniggpositive neuromyelitis optica spectrum disorder subgroup analysis randomized phase 3 prevent trial openlabel extension mult scler relat disord 2021 feb 20 50102849 doi 101016 jmsard2021102849 online ahead printabstractbackground eculizumab terminal complement inhibitor significantly reduced risk relapse compared placebo patients antiaquaporin4 immunoglobulin gpositive aqp4+ neuromyelitis optica spectrum disorder nmosd prevent trial report efficacy safety analyses asian patients prevent openlabel extension ole methods prevent doubleblind randomized phase 3 trial patients aqp4+ nmosd randomly assigned 21 receive intravenous eculizumab maintenance dose 1200 mg 2 weeks placebo patients completed prevent receive eculizumab ole analyses performed prespecified subgroup asian patients results 143 patients enrolled 52 364 included asian subgroup eculizumab n 37 placebo n 15 45 asian patients received eculizumab ole asian patients 865 received concomitant immunosuppressive therapy prevent one adjudicated relapse occurred patients receiving eculizumab six occurred patients receiving placebo asian subgroup hazard ratio 005 95 confidence interval 001035 p 00002 estimated 952 asian patients remained relapsefree 144 weeks eculizumab treatment upper respiratory tract infections headache nasopharyngitis common adverse events eculizumab asian subgroup conclusion eculizumab reduces risk relapse asian patients aqp4+ nmosd benefitrisk profile similar overall prevent population benefits eculizumab maintained longterm therapy clinical trial registration clinicaltrialsgov identifiers nct01892345 prevent nct02003144 openlabel extension pmid33676197 doi101016 jmsard2021102849,0.0
multiphaseted problems tdp43 selective neuronal vulnerability als cell mol life sci 2021 mar 11 doi 101007 s0001802103792z online ahead printabstracttransactive response dnabinding protein 43 kda tdp43 encoded tardbp gene evolutionarily conserved heterogeneous nuclear ribonucleoprotein hnrnp regulates multiple steps rna metabolism cytoplasmic aggregation characterizes degenerating motor neurons amyotrophic lateral sclerosis als als cases cytoplasmic tdp43 aggregation occurs absence mutations coding sequence tardbp thus major challenge als research understand nature pathological changes occurring wildtype tdp43 explore upstream events intracellular extracellular milieu promote pathological transition tdp43 despite inherent obstacles analyzing tdp43 dynamics vivo motor neurons due anatomical complexity inaccessibility recent studies using cellular animal models provided important mechanistic insights potential links tdp43 motor neuron vulnerability als review intended provide overview current literature function regulation tdp43containing rnp granules membraneless organelles revealed various models discuss potential mechanisms tdp43 can cause selective vulnerability motor neurons alspmid33709256 doi101007 s0001802103792z,0.0
feasibility efficacy physical activity intervention managing restless legs syndrome multiple sclerosis results pilot randomized controlled trial mult scler relat disord 2021 feb 10 50102836 doi 101016 jmsard2021102836 online ahead printabstractbackground pilot randomized controlled trial examined feasibility efficacy physical activity behavior change intervention improving restless legs syndrome rls severity secondary sleep outcomes among sample adults multiple sclerosis ms methods participants ms n15 randomly assigned intervention n8 waitlist control n7 conditions physical activity intervention delivered 16week period outcomes assessed baseline immediately following 16week period conditionsresults significant positive effect intervention overall rls severity p01 243 severity night p03 235 severity day resting p01 244 severity day active p01 261 nonsignificant improvements rls severity falling asleep p33 209 significant positive effects sleep satisfaction p01 249 nonsignificant improvements selfreported global sleep quality p35 208 significant intervention effect selfreported time bed p03 237 total sleep time p03 236 nonsignificant improvements selfreported sleep latency p08 225 sleep efficiency p27 211 daytime sleepiness p52 204 p35 208 p51 204 significant effect intervention devicemeasured sleep qualityconclusions provide preliminary evidence feasibility efficacy physical activity intervention reducing rls severity potentially improving selfreported sleep outcomes adults ms clinicaltrialsgov identification number nct04061681pmid33618120 doi101016 jmsard2021102836,0.0
realworld effectiveness natalizumab treatment patients relapsing multiple sclerosis argentina chile arq neuropsiquiatr 2021 may 79 5 407414 doi 101590 0004282xanp20200303abstractbackground realworld effectiveness natalizumab people relapsing multiple sclerosis pwrms argentina chile reportedobjective evaluate effectiveness natalizumab treatment pwrms argentina chile clinical practicemethods conducted multicenter retrospective observational study reviewed medical records pwrms treated natalizumab least one year without interruption ms treatment lasted 12 weeks analyzed changes annualized relapse rate arr expanded disability status scale edss score magnetic resonance imaging mri results enrolled 117 pwrms treated natalizumab natalizumab treatment associated significant reduction arr baseline one year two years treatment 197 006 009 respectively p001 time point baseline edss scores reduced 071 073 points one two years respectively p001 worsening disability observed 829 675 pwrms one two years respectively improvement disability 444 one year 393 two years natalizumab treatment number relapserelated hospitalizations significantly reduced p001 mri lesions new enlarging t2 gadoliniumenhancing significantly reduced compared baseline evidence disease activity observed 65 two years natalizumab treatmentconclusions natalizumab significantly reduced disease activity pwrms argentina chile clinical practice natalizumab also decreased number hospitalizations compared prenatalizumab treatmentpmid34161529 doi101590 0004282xanp20200303,0.0
differentiation multiple sclerosis neuromyelitis optica spectrum disorders multiparametric quantitative mri using convolutional neural network j clin neurosci 2021 may 875558 doi 101016 jjocn202102018 epub 2021 mar 11abstractmultiple sclerosis neuromyelitis optica spectrum disorders neuroinflammatory diseases overlapping clinical manifestations developed convolutional neural network model differentiates two based magnetic resonance imaging data thirtyfive patients relapsingremitting multiple sclerosis eighteen age sex disease duration expanded disease status scalematched patients antiaquaporin4 antibodypositive neuromyelitis optica spectrum disorders included study patients scanned 3t scanner using multidynamic multiecho sequence simultaneously measures r1 r2 relaxation rates proton density r1 r2 proton density maps analyzed using convolutional neural network model avoid overfitting small dataset aimed separate features images specific image common group based squeezenet used common features classification leaveoneout cross validation performed evaluate performance model area receiver operating characteristic curve developed convolutional neural network model differentiating two disorders 0859 sensitivity multiple sclerosis neuromyelitis optica spectrum disorders accuracy 800 833 811 respectively conclusion developed convolutional neural network model differentiates multiple sclerosis neuromyelitis optica spectrum disorders designed avoid overfitting small training datasets proposed algorithm may facilitate differential diagnosis diseases clinical practicepmid33863534 doi101016 jjocn202102018,0.0
synergistic neuroprotective effects fingolimod mesenchymal stem cells msc experimental autoimmune encephalomyelitis immunol lett 2021 mar 4s01652478 21 00033x doi 101016 jimlet202103003 online ahead printabstractfingolimod gilenya effective oral medication approved relapsingremitting multiple sclerosis ms albeit less effective chronic disease main mechanism action peripheral immunomodulation neuroprotective effects may also involved mesenchymal stem cells msc shown exert immunomodulatory neurotrophic effects model multiple sclerosis experimental autoimmune encephalomyelitiseae use combination treatments chronic diseases ms long advocated may result improvement beneficial effects one tested vitro effects fingolimod msc vivo effect combination treatment model eae fingolimod affect detrimental way basic features mscs promoted migration ability neurotrophic factors secretion suppressed production proinflammatory cytokines astrocytes vitro vivo combined treatment fty720 msc either intravenous intracerebroventricular route administration resulted synergistic clinical beneficial effects compared fty720 msc alone paralleled significant reduction inflammatory cns infiltrations axonal loss data may indicate synergism fingolimod msc may support future combinations immunomodulatory drugs cellular therapies improvement benefits progressive forms mspmid33676976 doi101016 jimlet202103003,1.0
mri topography lesions related internuclear ophthalmoplegia patients multiple sclerosis ischemic stroke j neuroimaging 2021 apr 1 doi 101111 jon12847 online ahead printabstractbackground purpose internuclear ophthalmoplegia dysfunction conjugate eye movements caused lesions affecting medial longitudinal fasciculus mlf multiple sclerosis ms ischemic stroke represent common pathophysiologies magnetic resonance imaging mri allows localizing lesions affecting mlf comprehensive comparative studies exploring potential different spatial characteristics lesions affecting mlf missing nowmethods retrospectively investigated mri examinations 82 patients 40 patients ms 42 patients ischemic stroke lesion localization brainstem segmented 1 pontomedullary junction 2 mid pons 3 upper pons 4 mesencephalonresults corresponding lesions affecting mlf observed 29 40 725 ms 38 42 905 stroke patients compared stroke patients ms patients significantly lesions multiple locations p 001 stroke patients showed lesions level mesencephalon p 001 lesions level pontomedullary junction mid upper pons statistically differ groupsconclusion results demonstrate multiple lesions affecting mlf make inflammatorydemyelination due ms likely lesion localization level mesencephalon favors ischemiapmid33793026 doi101111 jon12847,1.0
genetic variations psma6 psmc6 proteasome genes associated multiple sclerosis response interferonbeta therapy latvians exp ther med 2021 may 21 5 478 doi 103892 etm20219909 epub 2021 mar 12abstractseveral polymorphisms genes related ubiquitinproteasome system exhibit association pathogenesis prognosis various human autoimmune diseases previous study reported association multiple sclerosis ms psma3rs2348071 polymorphism latvian population current study aimed evaluate psma6 psmc6 genetic variations interaction rs2348071 susceptibility ms risk response therapy latvian population psma6rs2277460 rs1048990 psmc6rs2295826 rs2295827 genotyped ms case control study analysed terms genotypeprotein correlation network possible association disease alleles single multilocus genotypes haplotypes studied loci assessed response therapy evaluated terms evidence disease activity best knowledge present study first report single multiloci variations psma6 psmc6 psma3 proteasome genes may contributed risk ms latvian population results current study suggested potential psma6rs1048990 independent marker prognosis interferon therapy response genotypephenotype network presented current study provided new insight pathogenesis ms perspectives future pharmaceutical interventionspmid33767773 pmcpmc7976443 doi103892 etm20219909,0.0
generation characterization human induced pluripotent stem cell line metui001a 25yearold male patient relapsingremitting multiple sclerosis stem cell res 2021 may 53102370 doi 101016 jscr2021102370 epub 2021 apr 27abstractmultiple sclerosis chronic disease characterized inflammation demyelination axonal damage central nervous system established induced pluripotent stem cell ipsc line metui001a peripheral blood mononuclear cells 25yearold male individual clinically diagnosed relapsingremitting multiple sclerosis rrms using integrationfree sendai reprogramming method demonstrated ipscs free exogenous sendai reprogramming vectors normal male karyotype express pluripotency markers differentiate three germ layers ipsc line can serve valuable resource generate cellular model systems investigate molecular mechanisms underlying rrmspmid34087999 doi101016 jscr2021102370,1.0
physician compensation united states lens ms neurologist mult scler relat disord 2021 feb 17 50102847 doi 101016 jmsard2021102847 online ahead printabstractpurpose review explore elements typically considered determining physician compensation united states examine compensation neurologists expertise multiple sclerosis ms care commensurate neurological specialists medical specialists also employ complex therapies eg oncologyrecent findings complexity diagnosis management ms requires increasing specialization additionally changing models delivery ms care resulted ms neurologist generating significant contribution margins fact revenue compensation ratio ms neurologist may significantly higher discipline neuroscience service lines however contribution margin often key justification compensation interventional intensive care practitioners neuroscience service lines generally considered ms neurologists compensation compensation models ms neurologists typically depend heavily absolute number relative value units associated evaluation management em codes making fields neurology financially attractive traineessummary considering shortage ms specialists demands discipline revenue compensation ratios ms neurologist significantly undercompensated relative neurological specialists physicians disciplines compensating ms neurologist appropriately supporting necessary infrastructure ms care will likely attract trainees discipline help reverse current scarcity ms neurologists united statespmid33618121 doi101016 jmsard2021102847,0.0
evaluation cognitive benefits intrathecal baclofen pump implantation people intractable multiple sclerosis related spasticity mult scler relat disord 2021 feb 10 50102831 doi 101016 jmsard2021102831 online ahead printabstractbackground spasticity common problematic symptom multiple sclerosis one third patients failing first line therapies intrathecal baclofen safe efficacious option treatment resistant spasticity anecdotally patients report improved concentration cognitive performance switching intrathecal baclofen itb systemic medicationsaim explore whether subjects proceed itb pump implantation spasticity management reduce oral antispasticity agents will improved cognitive functionmethods subjects admitted trial itb via lumbar puncture subsequent pump implantation spasticity cognitive measures itb trial 3 months post implant recorded paired ttest wilcoxon signed ranks test used within subject change effect sizes cohens dz calculated subgroup analysis 2 1 spasticity medications baseline performedresults 27 subjects ms completed per protocol mean age 46 years 26 56 disease duration 15 years 6 26 rrms 3 spms 17 ppms7 majority multiple spasticity medications spasticity scores significantly improved post pump implant mean itb dose 3 months 143 mcg day 19 discontinued treatments spasticity deterioration cognitive mood measure improvement moderate effect size found backwards digit span d041 p0059 hads anxiety d037 p0097 fatigue severity scale score decreased substantially d081 p0005 small improvements symbol digit modalities test score d024 sustained attention response task response time d023 nonsignificant performance measures change effect sizes larger subgroup 2 oral spasticity medications baseline compared group 1 medication sdmt d042 vs d007 backwards digit span 045 vs 028 hadsanxiety 039 vs 032 hadsdepression d032 vs 005 fss d 114 vs 042 conclusions pilot study exploring impact itb cognition spasticity scores improved universally beneficial effects measures fatigue anxiety auditory attention verbal working memory found improvement speed processing withdrawing higher doses oral medication also demonstrated suggesting switching itb added cognitive psychological benefits people mspmid33618123 doi101016 jmsard2021102831,0.0
randomized pilot trial oral prednisone taper vs placebo following iv methylprednisolone multiple sclerosis relapses effects adrenal function clinical efficacy mult scler relat disord 2021 feb 24 50102867 doi 101016 jmsard2021102867 online ahead printabstractwe performed pilot trial investigating effect steroid taper adrenal function safety measures acute ms relapses twentyfive patients randomized either prednisone taper n12 placebo n13 3 days intravenous methylprednisolone patient showed signs adrenal insufficiency time cortisol response acth significantly increased baseline 6 months groups patients remained clinically radiologically stable prednisone taper experienced frequently mood disorders hyperglycaemia weight increase confirmed sufficiently powered studies results question need steroid taper following shortterm intravenous methylprednisolonepmid33677411 doi101016 jmsard2021102867,0.0
betaendorphin opioid growth factor biomarkers physical ability multiple sclerosis mult scler relat disord 2021 feb 27 50102868 doi 101016 jmsard2021102868 online ahead printabstractbackground multiple sclerosis ms autoimmunemediated degenerative disorder increased peripheral inflammation disrupting blood brain barrier increasing msrelated healthcare costs requirement validate minimally invasive biomarkers become imperativemethods relapsingremitting ms patients disease modifying therapies consented penn state health ms clinic provide blood samples analyses serum cytokines endogenous opioid peptides well complete msqol54 surveyresults serum ogf levels ms patients glatiramer acetate mean 326 pg ml dimethyl fumarate mean 1933 pg ml natalizumab mean 3934 pg ml significantly elevated p 001 compared healthy controls mean 9846 pg ml individuals elevated ogf levels also increased levels tnf r 078 il17a r 081 patients treated glatiramer acetate significant p 001 elevations serum endorphin levels analyses msqol 54 data showed significant differences physical mental composite scores treatment groups however serum levels endorphin direct correlation physical health composite score r 070 treatments serum vitamin d levels indirect relationship 25foot walk test times r 047 conclusion regression cohort data suggest serum levels ogf endorphin vitamin d potential biomarkers physical disease status mspmid33677409 doi101016 jmsard2021102868,0.0
regulation expression human endogenous retroviruses hervs elements fetal development possible role development cancer neurological diseases apmis 2021 mar 8 doi 101111 apm13130 online ahead printabstracthuman endogenous retroviruses hervs remnants ancient retroviral germline infections herv sequences silenced somatic cells interest emerging involvement herv derived transcripts proteins human physiology disease hervw encoded protein syncytin1 coopted fetal physiology plays role trophoblast formation altered herv transcription expression herv derived proteins associated various cancer types neurological diseases multiple sclerosis ms implication hervs potential mediators health disease suggests important roles regulatory mechanisms alterations physiological pathological processes regulation herv sequences mediated wide variety mechanisms focus review selected aspects including epigenetic mechanisms cpg methylation histone modifications hp1h3k9me axis viral transactivation events regulatory perspectives transient stimuli microenvironment increasing knowledge regulation herv sequences will contribute understanding complex pathogeneses may pinpoint potential targets better diagnosis treatment complex diseases mspmid33683784 doi101111 apm13130,0.0
association familial mediterranean fever multiple sclerosis case series jir cohort systematic literature review mult scler relat disord 2021 feb 10 50102834 doi 101016 jmsard2021102834 online ahead printabstractintroduction familial mediterranean fever fmf frequent monogenic autoinflammatory disorder leads uncontrolled production interleukin il 1 multiple sclerosis ms inflammatory disease central nervous system development seems partly correlated il1 levels hypothesized fmf associated ms aim describe features patients displaying diseases investigate mefv mutation rate ms patientsmethods patients definite ms retrieved cohort fmf patients reference center rare autoinflammatory diseases amyloidosis ceremaia also performed systematic literature review articles pubmed published 1990 2020results twentyfour patients included case series five patients 13 cohort 364 19 patients literature sex ratio 21 mean age diagnosis fmf 19 years old ms 29 years old seven studies investigating mefv mutation rate ms patients included three studies found higher mutation rate ms patients control groupconclusion fmf ms features comparable patients unrelated diseases mefv mutation carriage positively correlated ms however ms prevalence fmf patients higher expected healthy population lesser extent fmf prevalence ms patients higher expected healthy population difference might significant data suggest fmf associated ms studies needed investigate potential causal associationpmid33609923 doi101016 jmsard2021102834,0.0
role language ability verbal fluency individuals multiple sclerosis mult scler relat disord 2021 feb 16 50102846 doi 101016 jmsard2021102846 online ahead printabstractbackground cognitive deficits memory processing speed welldocumented individuals multiple sclerosis ms language largely considered intact verbal fluency deficits observed ms often attributed impaired processing speed executive functions rather language ability current study evaluates contribution various cognitive factors verbal fluency including language ability oralmotor speed processing speed executive functionsmethods analyzed preexisting data seventyfour 74 individuals ms completed battery neuropsychological tests designed assess individual ability various cognitive factors conducted linear multiple regression analyses letter category verbal fluency outcome variables performance cognitive domains eg processing speed executive functioning predictorsresults vocabulary processing speed predicted letter fluency vocabulary predicted category fluency findings suggest observed verbal fluency deficits ms may reflect impaired language ability processing speedconclusion propose research language ability ms needed determine comprehensive neuropsychological test batteries persons ms include tests language ability fully understand cognitive profile given patient given importance language ability may necessary conduct thorough assessment language individuals ms experience deficit domainpmid33626431 doi101016 jmsard2021102846,0.0
mirna467b inhibits th17 differentiation targeting eif4e experimental autoimmune encephalomyelitis mol immunol 2021 feb 20 1332333 doi 101016 jmolimm202102008 online ahead printabstractmultiple sclerosis ms animal model experimental autoimmune encephalomyelitis eae neuroinflammatory autoimmune diseases characterized axonal loss demyelination neurodegeneration central nervous system overactivation cd4+ t cells especially migration th1 th17 subsets central nervous system cns leads secretion inflammatory mediators destruction contact neurons activated macrophages can result series neurocognitive motor deficits study intended explore role mirna467b regulating th cell development eae found level mirna467b decreased eukaryotic initiation factor 4 f eif4e increased lymph nodes cns eae peak eif4e confirmed direct target mirna467b overexpression mirna467b suppress percentage cd4+ il17+ cells eae cd4 + t cells vitro addition also identified mirna467b suppress th17 cell differentiation targeting eif4e vitro furthermore injecting mirna467b mimics caudal vein eae mice contributed less inflammation peripheral lymphoid organs cns alleviated disease severity taken together findings imply mirna467b inhibits differentiation function th17 cells targeting eif4e thereby alleviating eaepmid33621940 doi101016 jmolimm202102008,1.0
maximal muscle strength fatigability three lower limb muscle groups associated walking capacity fatigability multiple sclerosis exploratory study mult scler relat disord 2021 feb 10 50102841 doi 101016 jmsard2021102841 online ahead printabstractbackground muscle fatigability walking fatigability prevalent persons ms pwms associations remains unclear aim study examine association muscle strength fatigability isometric concentric protocols three different muscle groups association walking capacity walking fatigabilitymethods twentyseven pwms 13 healthy controls hc included exploratory study participants performed sixminute walking test 6mwt distance walked index dwi calculated measure walking fatigability cutoff score 10 three different muscle groups knee extensors ke knee flexors kf ankle dorsiflexors df isometric concentric muscle fatigability protocols fiisometric ficoncentric used quantify maximal voluntary contraction mvc muscle fatigability pearson spearman correlation coefficients linear regression models calculated establish association muscle strength fatigability walking capacity fatigabilityresults higher mvcs values muscle groups found hc compared pwms mainly walking fatigability p 005 fiisometric df lower pwms walking fatigability compared walking fatigability mvc ke kf df low moderate association walking capacity range r 052056 p 005 walking fatigability pwms range rrs 039050 p005 ficoncentric kf df ke associated walking fatigability r 039 rs 047 respectively p 005 contrast fiisometric muscle groups related walking capacity walking fatigabilityconclusion mvc ke kf df associated walking capacity walking fatigability concentric isometric muscle fatigability kf df associated walking fatigabilitypmid33621946 doi101016 jmsard2021102841,0.0
examining cognitive speed accuracy dysfunction youth young adults pediatriconset multiple sclerosis using computerized neurocognitive battery neuropsychology 2021 may 35 4 388398 doi 101037 neu0000729abstractobjective evaluated performance penn computerized neurocognitive battery pcnb tool assessing accuracy response time across four cognitive domains alongside symbol digit modalities test sdmt measure processing speed commonly used ms determined whether performance decrements likely detected measures accuracy versus response time pediatriconset multiple sclerosis poms methods performance sdmt accuracy pcnb tests belonging four domains executive function episodic memory complex cognition social cognition response time pcnb compared 65 poms patients age range 829 years 76 healthy controls hcs ancova associations overall pcnb score sdmt examined groups agreement classifying impairment assessed using cohens kapparesults poms patients age testing 183 40 years age poms onset 149 23 years demonstrated reduced accuracy relative hcs tests working memory attention inhibition verbal memory visuospatial processing adjusting response time p 002 patients demonstrated slower overall response time pcnb p 003 group differences sdmt meet significance p 03 performance pcnb sdmt correlated ms r 043 hc r 050 p 001 however degree agreement impairment minimal k 022 p 14 conclusion specific cognitive deficits exist independently slowed information processing speed poms may represent significant areas dysfunction delineation accuracy response time neuropsychological assessment important identify areas cognitive deficit poms psycinfo database record c 2021 apa rights reserved pmid34043389 doi101037 neu0000729,0.0
primary progressive multiple sclerosis brain nerve 2021 may 73 5 458465 doi 1011477 mf1416201786abstractprimary progressive multiple sclerosis ppms chronic inflammatory disease central nervous system leads demyelination neurodegeneration ppms characterized gradual accumulation disabilities may occur initial disease onset pathological processes underlying ppms complex include variety different mechanisms pathways including inflammation axonal degeneration microglial activation oxidation byproducts mitochondrial injury glutamate excitotoxicity currently diseasemodifying drug approved ppms japan however ocrelizumab humanized anticd20 monoclonal antibody approved ppms food drug administration addition diseasemodifying drugs demonstrated significant efficacy treatment ppms clinical trialspmid34006676 doi1011477 mf1416201786,1.0
drug safety multiple sclerosis reporting signal detection benefitrisk management rev neurol paris 2021 mar 31s00353787 21 004586 doi 101016 jneurol202101009 online ahead printabstractbackground pharmacovigilance pv rules emerged late 60searly 70s since time world health organization center international drug monitoring carries corresponding tasks multiple sclerosis ms chronic inflammatory demyelinating disease central nervous system generally starts young adults 20 40 years age last 25 years ms patients benefited development plethora disease modifying drugs dmd changes therapeutic armamentarium associated serious adverse reactions challenging health authorities neurologists involved treatment care ms patientsmethods present review aims describe ms dmds adverse drug reactions reported clinical trials postmarketing period important signal detection benefitrisk management disease now several examples reported illustrate different steps pv processesconclusion improvement pv system procedures led significant progress detection signals allowing better assessment benefitrisk balance implementation risk management plans ms treatments involvement neurologists essential improve knowledge benefitrisk balance drugs addition adverse drug reactions reporting persons ms encouragedpmid33812676 doi101016 jneurol202101009,1.0
corrigendum psychometric properties croatian version depression anxiety stress scale21 multiple sclerosis impact scale29 multiple sclerosis patients volume multiple sclerosis related disorders 50 2021 102850 mult scler relat disord 2021 may 50102873 doi 101016 jmsard2021102873 epub 2021 mar 4no abstractpmid33926693 doi101016 jmsard2021102873,0.0
sleep disorders possible predisposing attack factor neuromyelitis optica spectrum disorder nmosd casecontrol study clin neurol neurosurg 2021 mar 20 204106606 doi 101016 jclineuro2021106606 online ahead printabstractbackground sleep disturbances common neuromyelitis optica spectrum disorder nmosd great impact patients quality life according report 64 prevalence poor sleep quality nmosd patients therefore study done evaluate effect sleep disturbances nmosd acute exacerbationsmaterials methods casecontrol study conducted sina hospital 2019 total 60 patients nmosd diagnosis enrolled study 30 patients remission phase 30 patients hospitalized due acute attacks sleep disorders evaluated groups sleep quality assessed last month using pittsburgh sleep quality index psqi questionnaire data analyzed spss software version 21results among 60 patients evaluated control attack groups 867 female duration disease 6823 4289 months control group 6983 690 attack group mean age patients 3415 years old sleep quality unfavorable 30 56 patients control attack groups respectively significant differences two groups sleep latency habitual sleep efficiency sleep duration sleep disturbanceconclusion present study revealed significant difference sleep quality controls attack patients show direct relationship sleep disorders nmosd attackspmid33823399 doi101016 jclineuro2021106606,0.0
perceptions risk adherence care ms patients covid19 pandemic crosssectional study mult scler relat disord 2021 feb 23 50102856 doi 101016 jmsard2021102856 online ahead printabstractbackground covid19 pandemic raised concerns increased risk infection patients multiple sclerosis ms disrupted routine ms care aim study characterize extent ms patients perceptions risk adherence care pandemicmethods survey emailed patients large ms center new york city local peak pandemic assess perceptions infection risk adherence ms care including appointments laboratory studies mris taking diseasemodifying therapies dmt results 529 patients ms center responded survey two weeks april 2020 patients collectively showed concern becoming infected covid19 88 perceived higher infection risk due ms 70 taking dmts 68 patients frequently postponed appointments 41 laboratory studies 46 mris 41 noncompliance dmts less common 13 decisions alter usual recommendations care made patient often provider regarding adherence appointments 68 laboratory studies 70 mri 67 dmt 65 degree concern infection associated adherence appointments p0020 laboratory studies p0016 adherence mri dmts thirtyfive patients reported tested covid19 fourteen reported positive testconclusion patients ms highly concerned becoming infected local peak covid19 pandemic behaviors deviated originally recommended ms care common often selfinitiated patients overall compliant continuing dmtspmid33662858 doi101016 jmsard2021102856,0.0
gastrointestinal dysfunction neuroinflammatory diseases multiple sclerosis neuromyelitis optica acute autonomic ganglionopathy related conditions auton neurosci 2021 mar 13 232102795 doi 101016 jautneu2021102795 online ahead printabstractdisorders nervous system can produce variety gastrointestinal gi dysfunctions among lesions various brain structures can cause appetite loss hypothalamus decreased peristalsis presumably basal ganglia pontine defecation center barringtons nucleus decreased abdominal strain presumably parabrachial nucleus kollikerfuse nucleus hiccupping vomiting area postrema dorsal vagal complex addition decreased peristalsis without loss bowel sensation can caused lesions spinal long tracts intermediolateral nucleus peripheral nerves myenteric plexus recently neural diseases inflammatory etiology particularly affecting pns recognized contribute gi dysfunction review neuroinflammatory diseases potentially cause gi dysfunction among cns diseases multiple sclerosis neuromyelitis optica spectrum disorder myelin oligodendrocyte glycoprotein associated disorder autoimmune encephalitis peripheral nervous system diseases impacting gut include guillainbarre syndrome chronic inflammatory demyelinating polyneuropathy acute sensoryautonomic neuropathy acute motorsensoryautonomic neuropathy acute autonomic ganglionopathy myasthenia gravis acute autonomic neuropathy paraneoplastic syndrome finally collagen diseases sjogren syndrome systemic sclerosis celiac disease affect cns pns neuroassociated gi dysfunctions may predate present concurrently brain spinal cord peripheral nerve dysfunction patients may visit gastroenterologists physicians first neurological diagnosis made therefore awareness phenomena among general practitioners collaboration gastroenterologists neurologists highly recommended order early diagnosis optimal management well systematic documentation presentations treatmentpmid33740560 doi101016 jautneu2021102795,1.0
microglial changes associated meningeal inflammation multiple sclerosis nat rev neurol 2021 apr 12 doi 101038 s41582021004949 online ahead printno abstractpmid33846617 doi101038 s41582021004949,0.0
flow cytometric approach study glucocorticoid receptor expression immune cell subpopulations genetically engineered mice immunol lett 2021 mar 19s01652478 21 000481 doi 101016 jimlet202103010 online ahead printabstractglucocorticoids gcs constitute one powerful classes antiinflammatory agents used treatment plethora diseases related autoimmunity allergy cancer infection last two decades multiple studies using genetically engineered mice targeted deletions gc receptor gr individual cell types provided insights mechanisms gcs control immune system characterization gr expression mouse models however mostly relied analysis mrna expression reporter gene activity contrast approaches directly detecting gr protein cellular level scarce thus used flow cytometric method analyze mice gr gene locus disrupted help cre recombinase expressed control either lck lysm promoter measuring gr protein expression immune cell subpopulations unveiled efficient highly selective depletion strains knockout mice accordance expected cellular specificity employed promoters t cells myeloid cells respectively flow cytometric data well line analysis gr mrna expression magnetically sorted immune cell subpopulations obtained much quickly summary data indicate flow cytometry powerful tool define gr protein content single cell level studying function gcs immune systempmid33753134 doi101016 jimlet202103010,0.0
comparison simoa tm ella tm assess serum neurofilamentlight chain multiple sclerosis ann clin transl neurol 2021 apr 8 doi 101002 acn351355 online ahead printabstractwe compared simoatm ellatm immunoassays assess serum neurofilamentlight chain levels 203 multiple sclerosis patients ofsep hd study strong correlation 086 p 00001 platforms ellatm instrument overestimated values 17 data linear p 057 possible apply correction factor ellatm results simoatm serum neurofilamentlight chain levels measured ellatm correlated age edss significantly higher active multiple sclerosis suggesting assays equivalent can used routine clinical practicepmid33830650 doi101002 acn351355,0.0
pharmacokinetics bioavailability monomethyl fumarate following single oral dose bafiertam monomethyl fumarate tecfidera dimethyl fumarate cns drugs 2021 mar 30 doi 101007 s40263021007999 online ahead printabstractbackground tecfidera dimethyl fumarate dmf approved product treatment relapsing forms multiple sclerosis monomethyl fumarate mmf active metabolite dmf responsible therapeutic efficacyobjective objective study determine whether two bafiertam capsules containing 95 mg mmf bioequivalent one tecfidera capsule containing 240 mg dmf prodrug mmfmethods singledose openlabel randomized twoway crossover study evaluating two treatments two periods washout interval treatments fifty healthy subjects randomized receive single dose test drug mmf 190 mg 2 95 mg delayedrelease capsules reference drug dmf 240 mg 1 240mg delayedrelease capsule blood samples obtained prior dosing prespecified time points 24 h postdose determine plasma concentrations mmf pharmacokinetic parameters mmf calculated including maximum observed concentration time reach maximum observed concentration apparent halflife drug plasma auc0t area plasma concentrationtime curve auc time zero dosing time last time point t measurable analyte concentration auc0inf auc0t plus extrapolated auc time t infinityresults geometric leastsquares mean ratios 90 confidence interval test drug mmf vs reference drug dmf 9680 921810164 9635 918110112 10484 955411505 auc0t auc0inf maximum observed concentration respectively two capsules bafiertam safe generally well tolerated common adverse event products flushing 60 51 bafiertam tecfidera respectivelyconclusions based statistical analysis results pharmacokinetic parameters mmf single oral dose two bafiertam dr 95 mg capsules bioequivalent single oral dose one tecfidera dr 240 mg capsuleclinical trial registration study retrospectively registered clinicaltrialsgov nct04570670 30 september 2020pmid33797063 doi101007 s40263021007999,0.0
endocrine crosstalk gut microbiome glial cells development disease j neuroendocrinol 2021 may 33 5 e12924 doi 101111 jne12924abstractglial cells make major cellular component nervous system glial development usually investigated perturbations host genetics although nonhostderived signalling molecules can also regulate glial cells indeed gut microbiome colonisation presence microbiomederived factors blood coincide glial cell development emerging data suggest gut microbiome can regulate gliogenesis myelination glial epigenetics neurodegenerative diseases characterised changes gut microbiome glial dysfunction perspective discusses ways microbiomederived molecules can engage crosstalk glial cells development dysfunctional glial diseasespmid34019340 doi101111 jne12924,1.0
exercise training cognition multiple sclerosis get smart trial protocol contemp clin trials 2021 feb 27106331 doi 101016 jcct2021106331 online ahead printabstractbackground objectives multiple sclerosis ms causes cognitive impairment approximately 50 cases disease modifying medications cognitive rehabilitation produce small positive effects cognition ms converging animal human research suggests aerobic exercise may improve cognition people ms definitive trials lacking describe design get smart study randomized controlled trial comparing effects aerobic exercise versus stretching toning cognition msmethods study singleblind parallel group randomized 11 controlled trial compares aerobic exercise training active control group consisting stretching toning exercises improving cognition participants nondepressed ambulatory nonexercising adults ms aged 1854 years average cognitive processing speed treatments designed generate equivalent outcome expectancies entailed supervised progressive exercise programs 3 times per week 40 min 6 month periodprojected patient outcomes primary hypothesis aerobic training group will demonstrate significantly greater cognitive processing speed compared control group end treatment phase 6 months measured composite paced auditory serial additon test oral symboldigit modalities test using intentto treat analyses secondary outcomes neuropsychological functioning cardiorespiratory fitness well participant reported outcomes depression sleep fatigue study findings will inform future research patient education clinical care policymakingtrial registration clinicaltrialsgov identifier nct02106052pmid33652128 doi101016 jcct2021106331,0.0
mri characteristics japanese macaque encephalomyelitis comparison human diseases j neuroimaging 2021 apr 30 doi 101111 jon12868 online ahead printabstractbackground purpose describe mri findings japanese macaque encephalomyelitis jme emphasis lesion characteristics lesion evolution normalappearing brain tissue similarities human demyelinating diseasemethods mri data obtained 114 japanese macaques 30 presenting neurological signs jme animals screened presence t2 weighted white matter signal hyperintensities animals behavioral signs jme additionally screened contrastenhancing lesions wholebrain quantitative t1 maps collected histogram analysis performed regression across age evaluate microstructural changes normal appearing brain tissue jme neurologically normal animals quantitative estimates bloodbrainbarrier bbb permeability gadoliniumbasedcontrast agent gbca obtained acute gbcaenhancing lesions longitudinal imaging data acquired 15 jme animalsresults one hundred seventythree focal gbcaenhancing lesions identified 30 animals demonstrating behavioral signs neurological dysfunction jme gbcaenhancing lesions typically focal ovoid demonstrating highest bbb gbca permeability lesion core similar acute focal multiple sclerosis lesions new gbcaenhancing lesions arose rapidly normalappearing tissue bbb permeability remained elevated weeks t1 values normalappearing tissue significantly associated age sex diseaseconclusions intense focal neuroinflammation key mri finding jme several features jme compare directly human inflammatory demyelinating diseases investigation jme combined development validation noninvasive imaging biomarkers offers substantial potential improve diagnostic specificity contribute understanding human demyelinating diseasespmid33930224 doi101111 jon12868,1.0
mitochondrial dysfunction traffic jams amyotrophic lateral sclerosis mitochondrion 2021 feb 24s15677249 21 000155 doi 101016 jmito202102008 online ahead printabstractneurodegenerative diseases characterized progressive neuronal loss anatomically physiologically accumulation protein cells mitochondria provide energy neuronal cells consuming 20 bodys oxygen mitochondria dynamic membranebound cell organelles function generate atp regulate calcium homeostasis produce reactive oxygen species alterations electron transport chain mutation environmental toxins reduced atp production calcium dyshomeostasis increased oxidative stress resulting mitochondrial dysfunction leading pathogenesis neurodegenerative diseases als als described loss upper lower motor neurons resulting progressive muscle denervation loss voluntary movements multiple shreds evidence literature regarding mechanism involved mitochondrial dysfunction possible therapeutic targets treat condition moreover different studies reported role different gene mutations malfunctions transport system responsible accumulation aggregation proteins inside brain cells accumulation aggregation proteins neuronal cells known neuronal traffic jam also plays leading role progressive neurodegenerative diseases review elucidated critical insights mitochondrial dysfunction neuronal traffic jam role initiation progression als moreover pharmacological targets possible conducts scenario also brought togetherpmid33639271 doi101016 jmito202102008,0.0
can serum glial fibrillary acidic protein gfap solve longstanding problem diagnosis monitoring progressive multiple sclerosis mult scler relat disord 2021 may 50102931 doi 101016 jmsard2021102931 epub 2021 mar 31no abstractpmid33926692 doi101016 jmsard2021102931,0.0
blunted vaccines responses ocrelizumab highlight need immunizations prior treatment mult scler relat disord 2021 feb 21 50102851 doi 101016 jmsard2021102851 online ahead printno abstractpmid33636615 doi101016 jmsard2021102851,0.0
induced pluripotent stem cells derived one 70yearsold male donor apoe4 4 alleles stem cell res 2021 may 53102395 doi 101016 jscr2021102395 epub 2021 may 13abstractapolipoprotein e apoe lipidbinding protein 2 3 4 allelic variants human 4 isoform apoe4 strongest genetic risk factor lateonset form alzheimers disease ad also associated multiple neurological disorders multiple sclerosis cerebrovascular disease induced pluripotent stem cells derived peripheral blood mononuclear cells 70yearold male donor apoe4 4 alleles background explore pathogenesis screen potential treatment methods neurodegenerative diseases newlydeveloped induced pluripotent stem cell line pluripotent markers well expressed addition generated cells displayed normal karyotype differentiation potentialpmid34088020 doi101016 jscr2021102395,0.0
fingolimod effective therapeutic strategy pediatric relapsingremitting multiple sclerosis two case reports neurol sci 2021 apr 27 doi 101007 s10072021052707 online ahead printabstractapproximately 310 patients multiple sclerosis ms onset childhood pediatric ms characterized relapsingremitting course high relapse rate 2010 fingolimod gilenya approved usa treatment relapsingremitting ms adults 2018 united states food drug administration european medicines agency expanded approved indications fingolimod include use children relapsing ms drug approved italy indication september 2020 describe two cases children relapsingremitting ms treated fingolimod irccs ospedale san raffaele multiple sclerosis center milan italy 2 years realworld data confirm fingolimod effective therapeutic strategy children relapsing ms use considered pediatric patients active diseasepmid33904006 doi101007 s10072021052707,0.0
healthcare access experiences persons ms explored candidacy framework health soc care community 2021 feb 19 doi 101111 hsc13320 online ahead printabstractcanada one highest rates multiple sclerosis ms world affecting 1 every 385 individuals neurodegenerative condition unpredictable variable symptom profile disease course making difficult manage canadians ms high users healthcare services however report multiple unmet needs high disease burden low satisfaction healthcare access healthcare vital health maintenance may explain poor experiences access often measured using utilisation proxy may fail capture complexities access experiences population faces candidacy framework offers alternative utilisation measures examining process accessing care considering impact social patterning health system environments process aim current study align experiences persons ms accessing healthcare services stages candidacy framework fortyeight individuals ms living across ontario recruited participate one five focus groups ten individual interviews analysis included first inductive phase using constant comparative methods followed deductive phase using content analysis candidacy framework able capture experiences shared persons ms including patientcentred care past experiences outcome expectation care outcomes propose concepts included refinements current framework providing thorough explanation experiences persons ms accessing care manage conditionpmid33606904 doi101111 hsc13320,0.0
roles leptin key effector cells rheumatoid arthritis immunol lett 2021 feb 27s01652478 21 000298 doi 101016 jimlet202102008 online ahead printabstractleptin adipokine sharing structural characteristics longchain helical cytokine family crucial role regulator energy homeostasis paid attention immunoregulatory function emerging evidence indicated roles leptin autoimmune diseases systemic lupus erythematous sle multiple sclerosis ms rheumatoid arthritis ra psoriasis implying leptin might involved autoimmune disorders definite exists immunocyte dysfunction ra patients growing data manifested leptin increased serum synovial fluid ra patients compared healthy controls suggesting leptin might take part pathogenesis ra aim review discuss currently know regard role leptin immune system effects ra crucial cells clarify role leptin pathogenesis ra beneficial treatment medical studypmid33652029 doi101016 jimlet202102008,0.0
generation rrms ppms specific ipscs platform modeling multiple sclerosis stem cell res 2021 apr 15 53102319 doi 101016 jscr2021102319 online ahead printabstractthe advent cellular reprogramming technology converting somatic cells induced pluripotent stem cells ipscs revolutionized understandings neurodegenerative diseases otherwise hard access model multiple sclerosis ms chronic demyelinating inflammatory disease central nervous system eventually causing neuronal death accompanied disabilities report generation several relapsingremitting ms rrms primary progressive ms ppms ipsc lines ms patients along age matched healthy controls peripheral blood mononuclear cells pbmc patient specific ipsc lines displayed characteristic embryonic stem cell esc morphology exhibited pluripotency marker expression moreover ms ipsc lines successfully differentiated neural progenitor cells npc subjecting neural induction furthermore identified elevated expression cellular senescence hallmarks rrms ppms neural progenitors unveiling novel drug target avenue ms pathophysiology thus study altogether offers rrms ppms ipsc cellular models good tool better understanding ms pathologies drug testingpmid33894548 doi101016 jscr2021102319,1.0
options symptomatic treatment chronic neurological gait disorders fortschr neurol psychiatr 2021 apr 23 doi 101055 a14725860 online ahead printabstractgait mobility impairments common relevant patients chronic neurological disorders reduces healthrelated quality life induces falls morbidity symptomatic treatment options therefore necessary order improve health status patients neurological disordersby means selective literature research focusing studies specific gaitrelated outcome measures discuss differential treatment options 1 hypokinetic gait disorders parkinsons disease normal pressure hydrocephalus vascular encephalopathy 2 gait unsteadiness ataxia sensory cerebellar ataxia 3 gait spasticity paresis due multiple sclerosis therapeutical options symptomatic treatment gait disorders comprise nonpharmacological pharmacological approaches address functional domains locomotion postural control modulation adaptability gaitpharmacological options orientated pathophysiology underlying diseases supportive physiotherapeutic interventions offer broader unspecific options treatment clinical conditions specifically disturb execution locomotion gait can also addressed provision physical therapy supportive deviceseffective options symptomatic treatment patients neurological gait disorders available applications options addressing pathophysiology underlying disease functional domainbased exercise physiotherapy program provision walking aides specific symptoms worsen gait performance can recommendedpmid33893628 doi101055 a14725860,0.0
comparative treatment effectiveness oral fingolimod conventional injectable disease modifying agents multiple sclerosis pharmacotherapy 2021 feb 28 doi 101002 phar2517 online ahead printabstractbackground fingolimod first approved oral disease modifying agent dma reduce relapses multiple sclerosis ms previous observational studies assessed effectiveness dmas relapse consider treatment switchobjective compare effectiveness oral fingolimod conventional injectable dmas using composite endpoint relapse treatment switch patients msmethods retrospective longitudinal study utilized ibm marketscan commercial claims encounters database 20102012 adults 18 years ms diagnosis icd9cm340 newly initiated dma included cox proportional hazards ph regression model weighted stabilized inverse probability treatment weights iptw robust sandwich estimator used evaluate composite endpoint time relapse treatment switch oral fingolimod injectable dma users oneyear followup treatment initiation additional analyses performed patients adherent proportion days covered pdc 08 dmas first three monthsresults incident study cohort consisted 1 997 ms patients initiated oral fingolimod 156 injectable 844 dmas proportion patients composite endpoint relapse dma treatment switch oral fingolimod injectable dma users found 1672 2716 respectively cox ph regression model stabilized iptw revealed fingolimod equally effective injectable dmas reducing risk experiencing composite endpoint relapse dma switch adjusted hazards ratio ahr 067 95 ci 043103 additional analysis among patients adherent also found significant difference composite endpoint ahr 070 95 ci 049115 oral fingolimod injectable dma usersconclusions oral fingolimod similar effectiveness injectable dmas reducing risk experiencing composite endpoint relapse treatment switch addition assessed independently oral fingolimod showed difference reducing time relapse dma treatment switch compared injectable dma userspmid33641232 doi101002 phar2517,0.0
fingolimod ameliorates imiquimodinduced psoriasiform dermatitis sequestrating interleukin17producing t cells secondary lymph nodes j dermatol sci 2021 apr 15s09231811 21 000773 doi 101016 jjdermsci202104004 online ahead printabstractbackground psoriasis chronic inflammatory skin disease interleukin il 17a plays key role pathogenesis psoriasis fingolimod available treatment multiple sclerosis exerts antiinflammatory effects sequestrating inflammatory lymphocytes secondary lymphoid tissues thymus effect fingolimod psoriasis reported yetobjective objectives investigate effect fingolimod psoriasis utilizing mice imiquimod imq induced psoriasiform dermatitis explore possibility fingolimod therapeutic agent psoriasismethods psoriasiform dermatitis induced imiquimod application murine shaved back skin six days fingolimod prepared phosphatebuffered saline pbs pbs alone control administered intraperitoneally daily days 0 5results fingolimod ameliorated imqinduced psoriasis dermatitis clinically histologically day 6 mrna expression level il17a lower skin fingolimodtreated mice pbstreated mice whereas higher inguinal lymph nodes fingolimodtreated mice pbstreated mice flow cytometric analyses revealed fingolimod reduced il17aproducing t cells infiltrating skin whereas increased cells inguinal lymph nodes fingolimod inhibited egress langerhans cells skin lymph nodesconclusion results demonstrated fingolimod showed effectiveness imqinduced psoriasiform dermatitis hindering emigration il17aproducing t cells lymph nodes skin suggest fingolimod promising candidate treatment psoriasispmid33888401 doi101016 jjdermsci202104004,0.0
effects motor control personalized neuromodulation multiple sclerosis fatigue brain topogr 2021 mar 3 doi 101007 s1054802100820w online ahead printabstractfatigue hidden symptom multiple sclerosis ms disease nevertheless impacts severely patients everyday life evidence indicates involvement sensorimotor network internodes communication basis symptom two randomized controlled trials rcts showed personalized neuromodulation called fatigue relief multiple sclerosis faremus efficaciously fights multiple sclerosis ms fatigue proof concept study tested whether faremus reverts alteration brainmuscular synchronization previously observed occurring fatigue cortico muscular coherence cmc studied 11 patients faremus 5day tdcs 15 ma 15 min per day anodal whole bodys somatosensory representation s1 via personalized mribased electrode 35 cm2 occipital cathode 70 cm2 faremus cmc observed mean frequency 315 16 hz gammaband positively correlated level fatigue p 027 faremus fatigue reduced average 28 33 baseline level cmc frequency reduced 266 15 hz p 022 thus forthcoming physiological betaband observed healthy people personalized s1 neuromodulation treatment ameliorating centralperipheral communication subtends simple everyday movements supports appropriateness neuromodulations aiming increasing parietal excitability fighting ms fatigue relationship centralperipheral features fatigue profile strengthens central peripheral origin symptompmid33656622 doi101007 s1054802100820w,0.0
therapeutic apheresis neurological disorders brain nerve 2021 may 73 5 425430 doi 1011477 mf1416201782abstracttherapeutic apheresis valuable therapeutic option various immunemediated human disorders therapeutic rationale based removal pathogenic autoantibodies inflammatory molecules complements cytokines chemokines accelerate disease activity time mechanisms immunemodulatory effects also suggested therapeutic apheresis applied guillainbarr syndrome chronic inflammatory demyelinating polyneuropathy myasthenia gravis multiple sclerosis neuromyelitis optica spectrum disorder nmosd antiaquaporin 4 antibody plays major pathogenic role plasma exchange plasma adsorption reported effective recently incidence prevalence autoimmune encephalitis increasingly reported comparison infective encephalitis often respond therapeutic apheresis therapeutic apheresis immunemediated neurological disorders described sectionpmid34006672 doi1011477 mf1416201782,1.0
correction efficacy acceptability s1p receptor treatment multiple sclerosis metaanalysis neurol sci 2021 mar 19 doi 101007 s1007202105137x online ahead printno abstractpmid33740152 doi101007 s1007202105137x,0.0
distinct roles monoamines multiple sclerosis bridge immune nervous systems brain behav immun 2021 mar 1s08891591 21 000957 doi 101016 jbbi202102030 online ahead printabstractthe monoaminergic neurotransmitters dopamine noradrenaline serotonin pivotal actors interplay nervous immune system due ability binding cellreceptors systems crucially regulating function within central nervous system periphery monoamines dysfunctional many neurological psychiatric diseases successfully used pharmacological targets multiple sclerosis ms one best examples neurological disease caused altered interaction nervous immune system emerging evidence supports dysregulation monoaminergic systems pathogenesis ms secondary inflammationinduced reduction monoamines synthesis structural damage monoaminergic pathways within brain review evidence monoamines key mediators neuroimmune interaction affecting ms pathogenesis course moreover discuss reduction dysfunction monoamines ms may contribute clinical features typical disease particularly fatigue depression finally summarize different drugs targeting monoamines currently evaluation potential efficacy treat ms well alleviate fatigue depression mspmid33662501 doi101016 jbbi202102030,0.0
patterns medical cannabis use among patients diagnosed multiple sclerosis mult scler relat disord 2021 feb 10 50102830 doi 101016 jmsard2021102830 online ahead printabstractobjective survey pattern benefits medical cannabis use mcu cross section persons multiple sclerosis pwms methods one hundred fifteen subjects completed 36question survey online paper queried aspects use cannabis including frequency use effect symptoms changes use prescription medications well asa number key demographic variables age gender disease duration clinical course etc subjects treated multiple sclerosis ms clinic connecticut enrolled connecticut medical marijuana program ctmmp results selfreported benefit cannabis use two symptoms ms associated relapsing remitting ms rrms vs progressive pms 3043 95 ci 10269028 p0038 less benefit two symptoms required wheelchair vs ambulated without assistance 246 95 ci 195797 p0016 general benefit cannabis use reported mood disorders p0001 insomnia p0001 sensory symptoms including pain p0001 muscle cramps spasms p0001 furthermore benefit also significantly associated symptom severity case insomnia 9735 95 ci 275134445 p0001 cramps spasms 5234 95 ci 126121729 p0014 significant proportion respondents stopped reduced prescription medications 86 vs 55 p0001 function finding cannabis effective prescription medications included opioids benzodiazepines muscle relaxers pain medicationsconclusion mcu among pwms can lead reduction discontinuation several categories prescription medications symptoms ms persons reporting benefit mcu tended milder form ms less disability contrast previous studies study confirms benefit cannabis several common ms symptoms extending findings show benefit can related baseline severity symptomspmid33636612 doi101016 jmsard2021102830,0.0
renal angiomyolipoma tuberous sclerosis complex longterm safety efficacy outcomes everolimus therapy actas urol esp 2021 feb 23s02104806 20 302588 doi 101016 jacuro202011004 online ahead printabstractintroduction renal angiomyolipoma frequent manifestation tuberous sclerosis complex tsc everolimus therapy recently established novel noninvasive therapeutic option limited real life longterm data analysis experience provides added value terms safety efficacymaterial methods descriptive analysis experience patients giant bilateral renal angiomyolipomas context tsc treated 10 mg oral everolimus daily median 715 months evaluated following parameters response rate duration reduction kidney size lesions prevention complications presentation toxicity causeresults confirm effectiveness treatment 4 young patients multiple bilateral angiomyolipomas median 12 519 cm maximum diameter june 2013 date continuous reduction lesion size decrease 30 volume 75 six months 50 half subjects two years still showing drug response absence complications bleeding glomerular filtration rate decline long term favorable safety profile without interruptions mildmoderate noncumulative adverse effects mostly within first year treatmentconclusion everolimus safe effective therapeutic option renal angiomyolipoma various manifestations tsc reproduced real life six years followuppmid33637375 doi101016 jacuro202011004,0.0
vaccinations patients multiple sclerosis review recommendations med j aust 2021 apr 18 doi 105694 mja251012 online ahead printno abstractpmid33866556 doi105694 mja251012,0.0
ultrasensitive immunoassay allows measurement serum neurofilament heavy multiple sclerosis mult scler relat disord 2021 feb 10 50102840 doi 101016 jmsard2021102840 online ahead printabstractbackground neurofilament heavy nfh promising biomarker neuroaxonal damage multiple sclerosis ms compared performance highsensitivity serumnfh immunoassays aim investigate value serumnfh biomarker msmethods measured serumnfh 76 ms patients simoa one commercial one inhouse luminex assays serumnfh measured immunoassay greatest sensitivity related clinical radiological outcomes age sexadjusted linear regression analysis biological outcomes cerebrospinal fluid csf nfh serum neurofilament light nfl csfnfl spearmans correlation analysisresults commercial simoa assay obtained 100 serumnfh detectability inhouse simoa 70 luminex 61 lowest coefficient variation cv duplicates 11cv inhouse simoa 22cv luminex 30cv serumnfh quantified commercial simoa assay associated disease duration standardized beta s 028 p 0034 t2 lesion volume s 023 p 0041 tended associate black hole count s 021 p 0084 expanded disease disability score edss normalized brain volume p010 furthermore serumnfh showed correlations csfnfh rho 027 p 0018 serumnfl rho044 p 0001 csfnflconclusions serumnfh can quantified highsensitivity technology crosssectionally observed weak correlations serumnfh ms disease burden parameters suggesting might utility serumnfh biomarker ms disease burdenpmid33626430 doi101016 jmsard2021102840,0.0
gamma knife radiosurgery treatment trigeminal neuralgia patients multiple sclerosis singlecenter retrospective study literature review world neurosurg 2021 feb 25s18788750 21 002679 doi 101016 jwneu202102074 online ahead printabstractobjective trigeminal neuralgia tn patients multiple sclerosis ms challenging condition manage treated gamma knife radiosurgery gkrs aim report assess safety efficacy durability gkrs treatment tn patients ms findings compared existing literature discussedmethods retrospectively reviewed patients institution underwent gkrs treatment tn secondary ms one years followup preoperative postoperative pain intensities facial numbness evaluated barrow neurological institute bni scores durability successful pain relief statistically evaluated kaplanmeier analysis prognostic role perioperative factors investigated analyzed using cox proportional hazards regressionresults 29 patients mstn underwent gkrs institution two patients underwent bilateral treatment four patients underwent repeat gkrs pain recurrence median period followup assessment 33 months rates reasonable pain reduction 1 3 5 years 70 57 57 respectively patients underwent repeat gkrs durable pain reduction prognostic factor successful pain reduction foundconclusions study shows gkrs treatment tn secondary ms safe effective procedure controlling pain short term often fails provide longterm pain control gkrs can safely repeated prolong time pain reductionpmid33640527 doi101016 jwneu202102074,0.0
absorption metabolism excretion vitro pharmacology clinical pharmacokinetics ozanimod novel sphingosine 1phosphate receptor agonist drug metab dispos 2021 mar 4dmdar2020000220 doi 101124 dmd120000220 online ahead printabstractozanimod approved treatment relapsing forms multiple sclerosis absorption metabolism excretion ozanimod investigated following single oral dose 10 mg 14cozanimod hydrochloride six healthy subjects vitro experiments conducted understand metabolic pathways enzyme involved metabolism ozanimod active metabolites total mean recovery administered radioactivity 63 26 37 recovered urine feces respectively based exposure major circulating components active metabolite cc112273 inactive metabolite rp101124 together accounted 50 circulating total radioactivity exposure ozanimod accounted 67 total radioactive exposure ozanimod extensively metabolized 13 metabolites identified including 2 major active metabolites cc112273 cc1084037 1 major inactive metabolite rp101124 circulation ozanimod metabolized three primary pathways including aldehyde dehydrogenase alcohol dehydrogenase cytochrome p450 cyp isoforms 3a4 1a1 reductive metabolism gut microflora primary metabolite rp101075 metabolized form major active metabolite cc112273 monoamine oxidase b undergoes reduction carbonyl reductases cbr form cc1084037 cyp2c8 mediated oxidation form rp101509 cc1084037 oxidized rapidly form cc112273 aldoketo reductase akr 1c1 1c2 3 11hydroxysteroid dehydrogenase hsd reversible oxidoreduction two active metabolites favors cc112273 ozanimod example illustrates need conducting timely radiolabeled human adme studies characterization disproportionate metabolites assessment exposure coverage drug development significance statement absorption metabolism excretion ozanimod characterized humans enzymes involved complex metabolism elucidated disproportionate metabolites identified activity metabolites determinedpmid33674268 doi101124 dmd120000220,0.0
prevalence neuromyelitis optica spectrum disorder belo horizonte southeast brazil mult scler relat disord 2021 feb 3 50102807 doi 101016 jmsard2021102807 online ahead printabstractbackground studies prevalence neuromyelitis optica spectrum disorder nmosd still scarce aim current study determine prevalence rate nmosd belo horizonte southeast brazil prevalence rate multiple sclerosis ms already establishedmethods observational study eligible patients meet 2015 international panel neuromyelitis optica diagnosis seen study center january 2000 february 2019 live belo horizonte prevalence rate nmosd estimated based number ms nmosd patients seen center period previously established prevalence ms belo horizonteresults study period 69 patients nmosd 60 870 females 44 638 nonwhites median age disease onset 367 472 years mean edss score 478236 mean arr 057043 antiaquaporin4 immunoglobulin testing available 61 884 patients 41 672 positive result period 280 ms patients seen considering local known prevalence rate ms 181 100 000 inhabitants estimated nmosd prevalence rate belo horizonte 452 100 000 95 ci 372543 inhabitantsconclusion prevalence rate nmosd belo horizonte high compared found studies reported datepmid33609926 doi101016 jmsard2021102807,0.0
mprage mp2rage uni translation via generative adversarial network improves automatic tissue lesion segmentation multiple sclerosis patients comput biol med 2021 feb 26 132104297 doi 101016 jcompbiomed2021104297 online ahead printabstractbackground objective compared conventional magnetizationprepared rapid gradientecho imaging mprage mri sequence specialized magnetization prepared 2 rapid acquisition gradient echoes mp2rage shows higher brain tissue lesion contrast multiple sclerosis ms patients goal work retrospectively generate realisticlooking mp2rage uniform images uni already acquired mprage images order improve automatic lesion tissue segmentationmethods task propose generative adversarial network gan multicontrast mri data 12 healthy controls 44 patients diagnosed ms retrospectively analyzed imaging acquired 3t using siemens scanner mprage mp2rage flair dir sequences train gan healthy controls ms patients generate synthetic mp2rage uni images images compared real mp2rage uni considered ground truth analyzing output automatic brain tissue lesion segmentation tools referencebased metrics well lesionwise true false positives dice coefficient volume difference considered evaluation statistical differences assessed wilcoxon signedrank testresults synthetic mp2rage uni significantly improves lesion tissue segmentation masks terms dice coefficient volume difference pvalues 0001 compared mprage segmentation metrics analyzed statistically significant differences found synthetic acquired mp2rage uniconclusion synthesized mp2rage uni images visually realistic improve output automatic segmentation toolspmid33711559 doi101016 jcompbiomed2021104297,0.0
hormonally active contraceptives part risks acknowledged unacknowledged linacre q 2021 may 88 2 126148 doi 101177 0024363920982709 epub 2021 jan 27abstracthormonal contraceptives market fifty years formulations changed basic mechanism action remained time numerous studies performed documenting side effects appear time within weeks months can serious impact health quality life effort made perform series comprehensive literature surveys better understand immediate longterm side effects agents results literature review uncovered number potential side effects acknowledged many noted prescribing information agents among unacknowledged side effects increased risk hiv transmission depot medroxyprogesterone acetate dmpa combination contraceptives breast cancer cervical cancer crohns disease ulcerative colitis systemic lupus erythematosus depression mood disorders suicides especially among women twentyfive years age younger first six months use multiple sclerosis interstitial cystitis female sexual dysfunction osteoporotic bone fractures especially progesteroneonly contraceptives fatty weight gain misleading prescribing information regarding cardiovascular thrombotic risks also noted women seeking birth control right informed educated risk avoidance use effective nonhormonal methods like fertility awareness methods one casethat dmpathe increased risk hiv acquisition conclusively demonstrated real unique drug considering availability numerous alternatives justification continued marketing dmpa publicsummary reviewed effect hormonal contraceptives womens health number potential side effects noted including increased risks breast cancer cervical cancer inflammatory bowel disease lupus multiple sclerosis cystitis bone fractures depression mood disorders suicides fatty weight gain female sexual dysfunction longacting injectable contraceptives increased risk getting hiv misleading prescribing information regarding risks heart attacks strokes blood clotting problems also noted women seeking birth control right know avoid risks using effective hormonefree fertility awareness methodspmid33897046 pmcpmc8033491 doi101177 0024363920982709,0.0
prophylactic therapeutic effects mogconjugated plga nanoparticles c57bl#x2f 6 mouse model multiple sclerosis adv pharm bull 2021 may 11 3 505513 doi 1034172 apb2021058 epub 2020 jul 26abstractpurpose multiple sclerosis ms debilitating neuroinflammatory disorder central nervous system believed result impaired immune response myelin components especially myelin oligodendrocyte glycoprotein mog efforts made bioconjugate mog peptides tolerogenic particles like poly lacticcoglycolic acid plga treating animal models autoimmune disorders accordingly aimed elucidate tolerogenic effects mogplga particles experimental autoimmune encephalomyelitis eae methods pgla nanoparticles synthesized using water oil water procedure next mog ovalbumin ova peptides covalently linked plga particles particles intravenously subcutaneously administered nine groups c57bl 6 mice eae induction brain tissues assessed infiltration immune cells tolerogenic effect vaccine also assessed quantity treg cells moreover amount interferon ifn interleukin10 il10 interleukin17 levels produced splenic lymphocytes quantified elisa results intravenous administration plga500mog3555 nanoparticles eae induction ameliorated eae clinical scores well infiltration immune cells brain spleen treatment increased cd4+cd25+foxp3+ treg population restored homeostasis ifn il10 il17 p values 00001 among splenocytes conclusion conjugation mog peptides plga nanoparticles significantly recovered clinical symptoms autoimmune response eae mogpgla particles potentially valuable evaluations hopefully progressing toward optimal approach can translated clinicpmid34513625 pmcpmc8421634 doi1034172 apb2021058,1.0
oxidative stress impaired oligodendrocyte precursor cell differentiation neurological disorders cell mol life sci 2021 mar 10 doi 101007 s00018021038020 online ahead printabstractoligodendrocyte precursor cells opcs account 5 resident parenchymal central nervous system glial cells opcs backup loss oligodendrocytes occurs due brain injury inflammationinduced demyelination remyelination also pivotal plastic processes learning memory adaptive myelination opc differentiation mature myelinating oligodendrocytes controlled complex transcriptional network depends high metabolic mitochondrial demand mounting evidence shows opc dysfunction culminating lack opc differentiation mediates progression neurodegenerative disorders multiple sclerosis alzheimers disease parkinsons disease importantly neurodegeneration characterised oxidative carbonyl stress may primarily affect opc plasticity due high metabolic demand limited antioxidant capacity associated cell type underlying mechanisms oxidative carbonyl stress disrupt opc differentiation remain enigmatic focus current research efforts review proposes role oxidative carbonyl stress interfering transcriptional metabolic changes required opc differentiation particular oligodendrocyte epi genetics cellular defence repair responses mitochondrial signalling respiration lipid metabolism represent key mechanisms oxidative carbonyl stress may hamper opc differentiation neurodegenerative disorders understanding oxidative carbonyl stress impacts opc function may pave way future opctargeted treatment strategies neurodegenerative disorderspmid33751149 doi101007 s00018021038020,1.0
pediatric inflammatory demyelinating disorders mimickers differentiate mri autoimmun rev 2021 mar 13102801 doi 101016 jautrev2021102801 online ahead printabstractmultiple sclerosis ms chronic immunemediated neurodegenerative disorder central nervous system cns clinical symptoms ms commonly manifest 20 40 years age approximately 3 10 ms patients report first inaugural events can occur earlier life even childhood thus include pediatric population prevalence ms onset childhood adolescence varies 20 40 ms cases according several extensive studies main imaging patterns pediatric inflammatory demyelinating disorders mimicking entities including multiple sclerosis neuromyelitis optica spectrum disorders acute disseminated encephalomyelitis mog myelin oligodendrocyte glycoprotein antibody disorder differential diagnoses will addressed article highlighting key points differential diagnosispmid33727154 doi101016 jautrev2021102801,1.0
efficacy fingolimod switching interferon beta1a adolescent multiple sclerosis case report neurol sci 2021 mar 16 doi 101007 s1007202105170w online ahead printabstractpediatriconset multiple sclerosis poms accounts approximately 210 cases multiple sclerosis ms associated higher levels disease activity adultonset ms including higher rates clinical relapse greater incidence new t2 lesions magnetic resonance imaging mri firstline therapy poms usually includes interferon glatiramer acetate however limited evidence randomized trials regarding safety efficacy diseasemodifying drugs pediatric patients fingolimod represents secondline therapy option relapsingremitting ms pediatric patients report case 14yearold girl diagnosis poms started interferon 1a firstline therapy switched fingolimod 12 months due radiologic progression clinical relapse patient subsequently experienced clinical stability showed minimal radiologic activity followup mri case demonstrates realworld clinical effectiveness safety fingolimod pediatric ms line results previous randomized observational studiespmid33723709 doi101007 s1007202105170w,0.0
accuracy brazilian version dymus questionnaire screening oropharyngeal dysphagia multiple sclerosis mult scler relat disord 2021 feb 19 50102772 doi 101016 jmsard2021102772 online ahead printabstractbackground oropharyngeal dysphagia common symptom many neurological diseases including multiple sclerosis ms early identification risk dysphagia neurological patients important early referral specialized evaluations oropharyngeal swallowing treatments dysphagia multiple sclerosis dymus questionnaire translated validated different countries last 10 years aimed analyze accuracy brazilian portuguese version dymus dymusbr questionnaire identifying dysphagia patients msmethods dymus questionnaire videofluorographic swallowing study vfss conducted 30 patients ms dysphagia identified least one abnormal response considered alarming dymus scores equal higher 3 patients considered dysphagia vfss one signs impairment efficiency safety swallowing detectedresults according initial selfassessment 37 n 11 patients ms selfreported dysphagia according dymusbr scores 53 n 16 patients ms classified dysphagia sensitivity specificity positive negative predictive values dymusbr questionnaire detection dysphagia measured vfss 50 95 confidence interval ci 2971 78 95 ci 6190 60 95 ci 4276 70 95 ci 6078 respectively area receiveroperating characteristic curve detecting dysphagia 64 95 ci 4979 conclusion accuracy dymusbr questionnaire poor detect mild swallowing impairment patients ms however suggest longitudinal followup patients low dymusbr scores early detection oropharyngeal dysphagiapmid33652231 doi101016 jmsard2021102772,0.0
efficacy core stability versus task oriented trainings balance ataxic persons multiple sclerosis single blinded randomized controlled trial mult scler relat disord 2021 feb 23 50102866 doi 101016 jmsard2021102866 online ahead printabstractbackground balance ataxic symptoms commonly encountered people multiple sclerosis pwms many intervention approaches proposed address balance pwms purpose study investigate efficacy adding core stability versus task oriented trainings traditional approaches balance ataxic pwmsmethods forty five ataxic relapsingremitting pwms sexes randomly assigned three identical groups control group cg treated conventional balance exercise program study groups gi ii gii received respectively additional training using core stability exercises task oriented trainings outcome measures recorded pre post study period included stability index si anterior posterior stability index apsi mediolateral stability index mlsi using biodex stability system addition berg balance scale bbs results post treatment results indicated significant improvement si apsi p005 nonsignificant improvement p005 mlsi bbs cg gi gii significant improvement balance measures p005 comparison post treatment results groups indicated significant improvement gii compared cg study measures gi showed non significant difference balance measures compared cg p005 conclusion pwms balance rehabilitation multimodal core stability exercises taskoriented training addition conventional balance training effective improve balance considered essential part training program balance rehabilitation ataxic pwms taskoriented training addition conventional balance rehabilitation seem favorable approachpmid33652233 doi101016 jmsard2021102866,0.0
low vitamin d tobacco use high bmi associated longterm disability progression multiple sclerosis mult scler relat disord 2021 jan 28 50102801 doi 101016 jmsard2021102801 online ahead printabstractbackground low vitamin d levels tobacco use high body mass index bmi linked adverse disease outcomes multiple sclerosis ms influence longterm disability progression remains unclear therefore explored whether modifiable lifestyle factors associated 10year clinical disability progression patients msmethods prospective study cohort 88 patients relapsingremitting ms completed randomized controlled study 3 fatty acids 2004 2008 24 months serum 25hydroxyvitamin d 25 oh d serum cotinine nicotine metabolite bmi repeatedly measured 2017 followup study conducted among 80 participants including disability assessment expanded disability status scale edss linear regression used explore associations lifestyle factors edss change 10 yearsresults higher seasonally adjusted 25 oh d levels associated lower 10year edss progression change edss per 1 sd increase 25 oh d model adjusted sex age baseline edss 045 point 95 ci 075 016 p0003 adjustments potential confounders related lifestyle disease status gave similar results association mainly driven low 25 oh d levels spring well seasonally adjusted levels 80 nmol l clear association found bmi cotinineconclusion lower 25 oh d levels apparently tobacco use higher bmi significantly associated worse longterm disability progression mspmid33636616 doi101016 jmsard2021102801,0.0
migraine associated brain anatomical alterations new data coordinatebased metaanalysis brain topogr 2021 feb 19 doi 101007 s10548021008246 online ahead printabstracta growing number studies investigate brain anatomy migraine using voxel vbm surfacebased morphometry sbm well diffusion tensor imaging dti purpose article identify consistent patterns anatomical alterations associated migraine first 19 migraineurs without aura 19 healthy participants included brain imaging study t1weighted mris dti sequences acquired analyzed using vbm sbm tractbased spatial statistics significant alterations gray matter gm volume cortical thickness cortical gyrification sulcus depth whitematter tract integrity observed however migraineurs displayed decreased white matter wm volume left superior longitudinal fasciculus second systematic review literature employing vbm sbm dti conducted investigate brain anatomy migraine metaanalysis performed using seedbased d mapping via permutation subject images sdmpsi gm volume wm volume cortical thickness data alterations gm volume wm volume cortical thickness whitematter tract integrity reported 72 50 56 33 published studies respectively spatial distribution direction disclosed effects highly inconsistent across studies sdmpsi analysis revealed neither significant decrease significant increase gm volume wm volume cortical thickness migraine overall day strong evidence specific brain anatomical alterations reliably associated migraine possible explanations conflicting literature discussed trial registration number nct02791997 registrated february 6th 2015pmid33606142 doi101007 s10548021008246,0.0
fingolimod firstline treatment pediatriconset multiple sclerosis case report neurol sci 2021 mar 12 doi 101007 s10072020050278 online ahead printabstractpediatriconset multiple sclerosis ms highly active aggressive course can devastating effect physical cognitive functioning child treated appropriately effective diseasemodifying drugs optimal treatment strategy pediatric ms currently unknown debate continues whether treatment escalation initiation highly active therapy provides better outcome present case 16yearold female diagnosed highly active relapsingremitting ms age onset 14 years received firstline treatment fingolimod within 1 year first recorded symptom since starting fingolimod course disease essentially stable new active lesions observed magnetic resonance imaging scans performed 3 12 months starting fingolimod treatment well tolerated data suggest case early treatment firstline fingolimod able slow disease progressionpmid33712907 doi101007 s10072020050278,0.0
concurrence multiple sclerosis glioblastoma mult scler relat disord 2021 mar 2 50102877 doi 101016 jmsard2021102877 online ahead printabstractintroduction glioblastoma rarely coincides multiple sclerosis although registries reported higher proportion brain tumorsmost glialthese events appear underreported relative contribution jc virus oncogenic virus disease modifying therapies may facilitate jc virus neurotropism tumorspecific immune evasion remain unknowncase report present case 64yearold woman developed primary glioblastoma eight years diagnosis multiple sclerosis dimethyl fumarateconclusion systematic reporting may help answer whether jc virus seropositivity certain disease modifying therapies confer higher risk glioblastoma patients multiple sclerosispmid33711579 doi101016 jmsard2021102877,0.0
spinal muscular atrophy health index italian validation diseasespecific outcome measure neuromuscul disord 2021 feb 9s09608966 21 000341 doi 101016 jnmd202102006 online ahead printabstractpatient report outcome measures spinal muscular atrophy sma represent potential complement observer rated scales can used better understand treatment response developed translated validated italian version spinal muscular atrophy health index smahi diseasespecific patient reported outcome measure questionnaire designed estimate patients perception disease burden testretest reliability assessed 37 patients 16 children aged 1217 21 adults excellent cohorts internal consistency additional 98 patients 24 children 74 adults also excellent cronbachs alpha 093 091 respectively children highest level disease burden generated lower limb dysfunction fatigue well perception decreased performance social situations patients adult cohort sitters complained problems upper limb functions well fatigue smahiit also able differentiate sma types according diseases severity results study demonstrate smahi can considered marker diseasespecific burden patients sma high testretest reliability internal validity italian patients aged 12 olderpmid33773884 doi101016 jnmd202102006,0.0
challenges multiple sclerosis care results international mixedmethods study mult scler relat disord 2021 feb 23 50102854 doi 101016 jmsard2021102854 online ahead printabstractbackground diseasemodifying treatment dmt selection people multiple sclerosis ms challenging neurologists advanced practice nurses apns ms care may facing knowledge confidence gaps screening patients initiate switch dmts assessing safety new dmts monitoring adverse events healthcare providers required demonstrate enhanced patient communication skills share treatment decisions assess treatment adherence better inform educational interventions need better understand challenges uncover causalities undertook international study across seven countries identify challenges neurologists apns may impact dmt choices optimum care people ms pwms methods mixed methods study involved two concurrent data collection phases qualitative phase semistructured interviews quantitative phase using online survey neurologists n333 apns n135 recruited canada france germany italy spain united kingdom united states participants minimum two years experience care pwms currently active clinical practiceresults triangulated analysis qualitative quantitative data identified multiple challenges apns mainly related diagnosing ms integrating new agents practice sequential dmt selection treatment monitoring providing personalized care specifically twothirds apns reported basic knowledge 2017 mcdonald criteria half reported knowledge gap new dmts available 51 skill gap integrating practice 58 apns expressed knowledge gap treatment sequencing 46 skill gap making decisions sequencing 62 fortyfour percent apns reported gap skills integrating patients goals treatment recommendations neurologists main challenges included managing side effects aligning care patients personal goals quality life qol specifically third neurologists reported basic knowledge characteristics treatment failure 35 32 reported basic skills identifying treatment failure skills needed integrate patients individual goals treatment recommendations reported none low 39 neurologists addition significant differences according years practice majority 9 14 confidence items respect discussing specific msrelated topics patients significant differences countries also identifiedconclusion complexity diagnosing ms variety available dmts pwms lead uncertainties even among specialized healthcare professionals addressed focused education training optimize care pwmspmid33690086 doi101016 jmsard2021102854,0.0
quantitative signal properties standardized mris correlate multiple sclerosis disability ann clin transl neurol 2021 may 4 doi 101002 acn351354 online ahead printabstractobjective enable use clinical magnetic resonance images mris quantify abnormalities normal appearing na white matter wm gray matter gm multiple sclerosis ms determine associations msrelated disability identification abnormalities heretofore required specialized scans routinely available clinical practicemethods developed analytic technique normalizes image intensities based intensity atlas quantification wm gm abnormalities standardized mris obtained clinical sequences gaussian mixture modeling applied summarize image intensity distributions t1weighted 3dflair t2weighted images 5010 participants enrolled multinational database ms patients collected imaging neuroperformance disability measuresresults intensity distribution metrics distinguished ms patients control participants based normalized nonlesional signal differences analysis revealed nonlesional differences relapsing ms versus progressive ms subtypes correlation nonlesional measures disability approximately three times greater total lesion volume disability measured using patient derived disease steps multivariate modeling revealed measures extralesional tissue integrity atrophy contribute uniquely approximately equally prediction msrelated disabilityinterpretation results support notion nonlesional abnormalities correlate strongly msrelated disability lesion burden provide new insight basis abnormalities na wm nonlesional abnormalities distinguish relapsing progressive ms distinguish progressive subtypes suggesting common progressive pathophysiology image intensity parameters existing biomarkers independently correlate msrelated disabilitypmid33943045 doi101002 acn351354,0.0
covid19 temporal relation onset multiple sclerosis mult scler relat disord 2021 feb 24 50102863 doi 101016 jmsard2021102863 online ahead printabstractneurological complications covid19 described present case 27yearold woman developed covid19 april 2020 continued present anosmia ageusia eight months later six months contracting covid19 developed dysesthesia hypoesthesia hyperreflexia magnetic resonance imaging showed demyelinating lesions two enhanced gadolinium positive oligoclonal bands spinal fluid patient developed multiple sclerosis temporal relationship covid19 believe sarscov2 led autoimmune disease virusinduced neuroimmunopathological conditionpmid33662859 doi101016 jmsard2021102863,1.0
human liverexpressed antimicrobial peptide 2 elevation cerebrospinal fluid bacterial meningitis brain behav 2021 apr 3e02111 doi 101002 brb32111 online ahead printabstractobjective study presence liverexpressed antimicrobial peptide 2 leap2 human cerebrospinal fluid csf measure concentrations neurological disordersmaterials methods identified presence leap2 human csf chromatographic analysis leap2specific enzyme immunoassay measured leap2 concentrations csf 35 patients neurological disordersresults csf leap2 concentrations bacterial meningitis group mean sd 932 376 ng ml significantly higher p 05 four groups psychosomatic disorder 056 015 ng ml peripheral autoimmune disease 100 060 ng ml multiple sclerosis 062 030 ng ml aseptic meningitis 159 069 ng ml conclusions first study identify presence human leap2 csf levels leap2 increased csf patients bacterial meningitis leap2 may potential biomarker bacterial meningitispmid33811478 doi101002 brb32111,0.0
major depressive disorder subtypes depression symptoms multiple sclerosis different compared general population j psychosom res 2021 feb 16 144110402 doi 101016 jjpsychores2021110402 online ahead printabstractobjective compare characterize major depressive disorder mdd subtypes ie pure atypical pure melancholic mixed atypicalmelancholic depression symptoms persons multiple sclerosis pwms persons without ms pw oms fulfilling dsm5 criteria past 12month mddmethods mdd pwms n 92 swiss multiple sclerosis registry compared pw oms n 277 swiss communitybased study epidemiological mdd diagnoses based minispike shortened form structured psychopathological interview rating social consequences epidemiology logistic multinomial regression analyses adjusted sex age civil status depression severity computed comparisons characterization latent class analysis lca conducted empirically identify depression subtypes pwmsresults pwms higher risk mixed atypicalmelancholic mdd subtype 222 95 ci 103480 compared pw oms mdd pwms specifically characterized higher risk two somatic atypical depression symptoms weight gain 691 95 ci 2202170 leaden paralysis 303 95 ci 135682 symptom irritable angry 318 95 ci 108939 conclusions mdd pwms characterized higher risk specific somatic atypical depression symptoms mixed atypicalmelancholic mdd subtype pure atypical mdd subtype however differentiate pwms pw oms given high phenomenological overlap ms symptoms mixed atypicalmelancholic mdd subtype represents particular diagnostic challengepmid33631437 doi101016 jjpsychores2021110402,0.0
shortterm data disease activity cognition mood stigma employment outcomes cohort patients primary progressive multiple sclerosis uppms study mult scler relat disord 2021 feb 23 50102860 doi 101016 jmsard2021102860 online ahead printabstractbackground primary progressive multiple sclerosis ppms long defined progressive disability accrual absence initial relapses however underlying neurodegenerative process seems accompanied central nervous system inflammation new classification defined multiple sclerosis courses according clinical radiological activity progression provide insight ppms activity according classification daily living aspectsmethods multicentre prospective cohort study including 55 adult patients ppms according 2010 mcdonald criteria within ten years neurologic symptom onset receiving diseasemodifying therapies past six months followed 12 months primary study endpoint percentage patients active disease based clinical relapses magnetic resonance activity disability progression cognitive function physical psychological impact depression symptoms stigma employment secondary endpointsresults eleven 256 patients exhibited multiple sclerosis activity throughout 12month study followup fourteen showed nonactive multiple sclerosis without progression 11 nonactive multiple sclerosis progression 6 active multiple sclerosis without progression 4 active multiple sclerosis progression one patient disease activity assessable progression cognitive function scores remained unchanged increased disease physical impact maintained disease psychological impact significantly decreased proportion patients depression symptoms stigma remained without significant changes well employment outcomesconclusion study shows onefourth ppms patients may exhibit disease activity one year disability progression approximately onethird without worsening cognitive function disease impact depression stigma employment outcomespmid33647591 doi101016 jmsard2021102860,0.0
anxiety depressive symptoms long mesial temporal epilepsy surgery prospective study epilepsy behav 2021 apr 8 118107936 doi 101016 jyebeh2021107936 online ahead printabstractbackground anxiety depressive symptoms prevalent patients refractory mesial temporal lobe epilepsy related hippocampal sclerosis mtlehs anterior temporal lobectomy atl aims 1 follow levels anxiety depressive symptoms longterm atl among patients refractory mtlehs 2 identify pre postsurgical variables associated levels anxiety depressive symptoms surgerymethods compared levels anxiety depressive symptoms determined hospital anxiety depression scale hads long atl mean 104 months range 70130 41 consecutive patients refractory mtlehs last followup september 2018 march 2020 also determined pre postsurgical variables independently associated hads scores surgeryresults scores hads subdomains related anxiety depression decreased significantly p 001 atl multiple linear regressions hadsanxiety scores surgery b 047 ci 95 020 075 p 0001 followup surgery b 007 ci 000 014 p 005 remain independently positively associated hadsanxiety scores surgery hadsdepression scores surgery independently positively associated hadsdepression scores surgery b 039 ci 95 010 076 p 001 worse seizure control surgery b 155 ci 95 023 287 p 002 conclusion anxiety depressive symptoms patients mtlehs significantly improved atl presurgical levels anxiety depressive symptoms respectively positively associated postsurgical levels symptoms length followup associated anxiety worse seizure control associated depressive symptoms atl results implications surgical management mtlehs patientspmid33839452 doi101016 jyebeh2021107936,0.0
neurovascular multiparametric mri defines epileptogenic seizure propagation regions experimental mesiotemporal lobe epilepsy epilepsia 2021 apr 5 doi 101111 epi16886 online ahead printabstractobjective improving identification epileptogenic zone associated seizurespreading regions represents significant challenge innovative brainimaging modalities tracking neurovascular dynamics seizures may provide new disease biomarkersmethods use multiparametric magnetic resonance imaging mri analysis 94 tesla examined elaborated combined multiple cellular cerebrovascular mri readouts imaging biomarkers epileptogenic seizurepropagating regions analyses performed experimental model mesial temporal lobe epilepsy mtle generated unilateral intrahippocampal injection kainic acid ka results ipsilateral epileptogenic hippocampi tissue t1 bloodbrain barrier bbb permeability gadolinium increased 4872 hours postka compared sham contralateral hippocampi bbb permeability endured spontaneous focal seizures 46 weeks along significant increase apparent diffusion coefficient adc blood volume fraction bvf simultaneously adc bvf augmented contralateral hippocampus region characterized electroencephalographic seizure spreading discrete histological neurovascular cell modifications tissue sclerosis next asked whether combining acquired mri parameters deliver criteria classify epileptogenic seizurespreading sham hippocampi experimental conditions time differentiate sham epileptogenic areas automatic multiparametric classification provided maximum accuracy 975 32 regions 4872 hours postka 100 60 regions spontaneous seizures stage differentiate sham epileptogenic seizurespreading areas accuracies automatic classification 931 42 regions 4872 hours postka 95 80 regions spontaneous seizure stagesignificance combining multiparametric mri acquisition machinelearning analyses delivers specific imaging identifiers segregate epileptogenic contralateral seizurespreading hippocampi experimental mtle potential clinical value findings critically discussedpmid33818790 doi101111 epi16886,0.0
psychometric properties croatian version depression anxiety stress scale21 multiple sclerosis impact scale29 multiple sclerosis patients mult scler relat disord 2021 feb 20 50102850 doi 101016 jmsard2021102850 online ahead printabstractobjectives depression anxiety stress physical disabilities common complaint people multiple sclerosis ms monitoring symptoms based selfreport questionnaires objective study determine psychometric properties croatian version depression anxiety stress scale21 dass21 multiple sclerosis impact scale29 msis29 people msmaterials methods included data 163 people ms registered association multiple sclerosis societies croatia amssc patients demographic information education level diseaserelated variables ascertained dass21 applied assessing depression anxiety stress msis29 scale used assessment physical psychological impact ms disease psychometric properties examined estimating validity reliability dass21 msis29 scale predictive validity dass21 subscales relevant demographic diseaserelated variables examined hierarchical regression modelresults croatian version three dass21 subscales two msis29 subscales excellent internal consistencies cronbachs alpha coefficients 088093 good convergent validity expressed intercorrelations dass21 msis29 subscales hierarchical regression analysis using msis29 subscales criterion variables showed consistent evidence predictive validity depression anxiety stress psychological impact predictive validity age edss anxiety physical impactconclusions croatian versions dass21 msis29 reliable valid scales people mspmid33636617 doi101016 jmsard2021102850,0.0
asymptomatic bradycardia first fingolimod dose pediatric patient multiple sclerosis case report neurol sci 2021 feb 26 doi 101007 s10072021050865 online ahead printabstractfingolimod currently approved us food drug administration european medicines agency treatment pediatric patients relapsingremitting multiple sclerosis rrms however transient asymptomatic bradycardia treatment initiation reported small population predisposed patients may result shortterm activation internalization desensitization gproteingated potassium channel ikach atrial myocyte membrane asymptomatic bradycardia without atrioventricular block generally selflimiting reported within first 6 h administration first oral dose fingolimod therefore patients initiating fingolimod treatment monitored initial period identify changes electrocardiogram heart rate may require treatment report case 17yearold female rrms received first fingolimod dose showed asymptomatic bradycardia resolved without treatmentpmid33635428 doi101007 s10072021050865,0.0
idiopathic intracranial hypertension multiple sclerosis mult scler relat disord 2021 feb 16 50102829 doi 101016 jmsard2021102829 online ahead printabstractunexplained elevated intracranial pressure occasionally develops individuals multiple sclerosis ms visual symptoms signs common conditions awareness association particularly relevant due increased incidence headache ms frequent overlap symptoms signs conditionspmid33626432 doi101016 jmsard2021102829,0.0
autoantibody profiles systemic sclerosis comparison diagnostic tests autoimmunity 2021 apr 518 doi 101080 0891693420211907842 online ahead printabstractobjectives autoimmune antibody profiling plays prominent role classification prognosis systemic sclerosis ssc last years novel autoantibodies discovered become available diagnostic assays however standardization autoimmune serology lacking may negative impact added value autoantibodies diagnosis prognosis ssc paper describe comparison commercially available diagnostic assays detection sscassociated autoantibodies explored coexistence multiple sscassociated autoantibodies within patientsmethods serum samples 347 patients nijmegen systemic sclerosis cohort included study patients fulfilled acr eular 2013 classification criteria ssc classified dcssc lcssc according leroy medsger criteria samples evaluated standard laboratory diagnostic tests detection sscspecific autoantibodies cenpa cenpb aca scl70 ata rna polymerase iii rp11 155 ara sscassociated autoantibodies fibrillarin thto pmscl75 pmscl100 rnp68 c ku nor90 pdgfr suppliers euroimmun dtek thermo fisher scientificresults found 79 patients positive one ssc autoantibodies overall high agreement observed diagnostic methods sscspecific autoantibodies listed acr eular criteria ata aca ara cohens kappa 053097 however lower agreement found sscassociated autoantibodies pmscl ku well sscspecific autoantibodies fibrillarin thto furthermore data revealed presence ata ara aca predominantly mutually exclusive fraction patients testing positive ata araconclusion data showed high concordance prevalent sscspecific autoantibodies different diagnostic assays standardisation low prevalent sscspecific sscassociated autoantibodies neededpmid33818234 doi101080 0891693420211907842,0.0
varicella zosterassociated acute retinal necrosis central nervous system complications natalizumab treated ms patients mult scler relat disord 2021 feb 10 50102838 doi 101016 jmsard2021102838 online ahead printabstractthere much awareness varicella zoster virus vzv associated central nervous system cns infections treatment natalizumab describe two natalizumab treated ms patients developed acute retinal necrosis combined cns vasculitis caused vzv natalizumab treated patients visual symptoms atypical optic neuritis promptly evaluated ophthalmologist currently total 12 cases natalizumabassociated vzv cns retinal infections reported literature two cases overview currently available data provide information prognosis treatment decisions rare devastating complicationpmid33609925 doi101016 jmsard2021102838,0.0
cholesterol autoxidation products 7ketocholesterol 7betahydroxycholesterol associated serum neurofilaments multiple sclerosis mult scler relat disord 2021 feb 26 50102864 doi 101016 jmsard2021102864 online ahead printabstractbackground serum neurofilament light chain snfl established marker neuroaxonal injury multiple sclerosis ms objectives investigate oxysterols produced nonenzymatic enzymatic cholesterol oxidation differentially associated snfl measurements msmethods longitudinal study included 62 relapsingremitting rrms 36 progressive ms pms patients baseline 5year followup measures serum levels 6 oxysterols snfl lipids oxysterols 24hydroxycholesterol 24hc 25hc 27hc 7hc 7hc 7ketocholesterol 7kc measured using liquid chromatographymass spectrometry snfl measured using single molecular array assay serum highdensity lipoprotein cholesterol hdlc lowdensity lipoprotein cholesterol ldlc levels obtained lipid profileresults enzymatically produced oxysterols 24hc 25hc 27hc 7hc associated snfl however baseline levels reactive oxygen species ros produced oxysterols 7kc p 0032 7hc p 00025 positively associated snfl levels followup followup 7kc p 0038 levels also associated followup snfl levels associations 7kc 7hc snfl remained significant adjusting ldlc hdlcconclusions 7kc 7hc produced rosmediated cholesterol oxidation associated neuroaxonal injury assessed snfl mspmid33677412 doi101016 jmsard2021102864,0.0
insights role b cells cortical pathology multiple sclerosis evidence animal models patients mult scler relat disord 2021 feb 16 50102845 doi 101016 jmsard2021102845 online ahead printabstractmultiple sclerosis ms chronic immunemediated disease central nervous system cns affects white gray matter although traditionally considered t cell mediated disease role b cell ms pathology become topic great research interest cortical lesions key feature progressive forms ms involved cognitive impairment worsening patients outcome lesions present pathognomonic hallmarks absence bloodbrain barrier bbb disruption limited inflammatory events reactive microglia neurodegeneration demyelination meningeal inflammation b cells located meninges either part diffuse inflammation part folliclelike structures strongly associated cortical damage function cd20expressing b cells ms highlighted success specific therapies using anticd20 antibodies possible roles b cells pathology go beyond ability produce antibodies also present antigens t cells secrete cytokines pathogenic protective within cns modulate t myeloid cell functions involved meningeal inflammation will review contributions b cells pathogenesis meningeal inflammation cortical lesions ms patients well preclinical animal modelspmid33636613 doi101016 jmsard2021102845,1.0
clinical neuroimaging characteristics mog autoimmunity children acquired demyelinating syndromes mult scler relat disord 2021 feb 10 50102837 doi 101016 jmsard2021102837 online ahead printabstractbackground myelin oligodendrocyte glycoprotein antibodies mogigg recently reevaluated biomarker acquired demyelinating syndromes ads central nervous system cns describe clinical neuroimaging features longterm outcome children ads cns associated mogigg methods patients underwent brain spinal cord magnetic resonance imaging mri lumbar puncture cerebrospinal fluid csf analysis mogigg aquaporin4 igg aqp4igg testing results fortyeight pediatric patients recruited mogigg detected 11 48 25 patients following clinical presentations encephalomyelitis em 8 11 73 optic neuritis 2 11 18 transverse myelitis tm 1 11 9 patients negative mogigg diagnosed multiple sclerosis ms n15 em n7 n7 neuromyelitis optica spectrum disorders nmosd n5 tm n2 encephalitis n1 mogigg positive patients younger disease onset frequently experienced encephalopathy epileptic seizures compared negative patients em inflammatory lesions involving optic nerves mri imaging frequent mogigg positive patients none patients mogigg became persistently seronegative followup although decrease mogigg titer observed patients mogigg showed good response therapy two patients presented relapses followup conclusion study supports distinction mog autoimmune oligodendrocytopathy unique disease entity clinical features different ms aqp4iggpositive nmosdpmid33636614 doi101016 jmsard2021102837,1.0
reduction risk pml natalizumab treated ms patients sweden effect improved pml risk surveillance mult scler relat disord 2021 feb 11 50102842 doi 101016 jmsard2021102842 online ahead printabstractbackground natalizumab ntz treatment multiple sclerosis ms associated increased risk progressive multifocal leukoencephalopathy pml aim present study evaluate impact pml risk assessment pml incidence ntz treated ms patientsmethods using information populationbased swedish ms registry retrospective cohort established patients treated ntz 20062018 effect pml incidence utilizing risk management plan including jc virus jcv serology analyzedresults december 2018 804 pml cases associated ntz therapy ms reported globally including 9 cases sweden estimated pml incidence 2018 sweden globally 07 0314 415 3944 per 1 000 person years respectively sweden jcv serology introduced 2012 pml risk assessment cumulative risk pml significantly lower 20122018 compared period 20062011 p0042 mean ntz exposure time 601 months sd 372 first period 20062011 326 months sd 220 second period 20122018 number patients treated ntz decreased number patients increased risk pml 19 end study periodconclusion since 2006 incidence pml associated ntz treatment ms decreased sweden findings suggest reduction due effective adoptation adherence established risk management plan implies switching patients increased pml risk ntz highly efficacious therapies less pronounced decline pml incidence recently observed france globallypmid33610957 doi101016 jmsard2021102842,0.0
persistence adherence ocrelizumab compared diseasemodifying therapies multiple sclerosis us commercial claims data j manag care spec pharm 2021 feb 24111 doi 1018553 jmcp202120413 online ahead printabstractbackground ocrelizumab ocr diseasemodifying therapy dmt relapsing primary progressive forms multiple sclerosis ms ocr given intravenous iv infusion twice year may improve adherence dosing schedule relative ms dmts require frequent administration realworld evidence persistence adherence patients ms ocr compared dmts limited objective examine persistence adherence ocr compared dmts ms united states methods analysis conducted pharmetrics plus commercial claims database included patients ms initiated new dmt april 2017 september 2018 patients required health plan enrollment 1 year dmt initiation subgroup analysis performed 18 months continuous enrollment dmt initiation persistence defined switching another dmt gap coverage initiated dmt 60 days postinitiation period proportion days covered pdc calculated total days covered dmt postinitiation period divided length time period 12 18 months pdc 08 considered adherent multivariable poisson regression models compared discontinuation nonpersistence nonadherence ocr users users dmts grouped administration route results total 4 587 patients ocr 1 319 injectable 1 051 oral 1 876 iv 341 included ocr group lowest proportion patients discontinuing 12 months 8 vs 28 32 43 iv oral injectable respectively highest mean pdc 93 vs 76 74 69 respectively compared patients initiating ocr adjusted relative risks rr 12month discontinuation 33 95 ci 2346 38 95 ci 3049 55 95 ci 4175 patients initiating iv oral injectable dmts respectively similarly patients initiating iv oral injectable dmts rrs 49 95 ci 3668 51 95 ci 3966 68 95 ci 5093 12month nonadherence compared ocr subgroup 2 913 patients 18 months continuous enrollment similar trends 17 ocr group discontinuing compared 40 41 55 iv oral injectable groups respectively trends 18 months consistent 12month analysis adjusted models conclusions patients initiating ocr superior persistence adherence 12 18 months followup compared patients initiating ms dmts longterm persistence adherence monitored ocr experience accrues realworld setting disclosures study funded genentech south san francisco ca member roche group engmann sheinson bawa ng employees genentech shareholders f hoffmanla roche basel switzerland pmid33624535 doi1018553 jmcp202120413,0.0
secondary progressive multiple sclerosis brain nerve 2021 may 73 5 450457 doi 1011477 mf1416201785abstractsecondary progressive multiple sclerosis spms defined slowly progressive deterioration clinical symptoms independent relapse following early relapsingremitting disease course diagnosis spms challenging usually retrospective lack reliable diagnostic tests also lack reliable clinical symptoms gait disturbance well evaluated clinical setting pathogenic mechanisms driving spms poorly understood therapy spms remains limited assumed characteristic features neurodegeneration observed spms caused chronic inflammation compartmentalized t b cells periphery glial mitochondrial dysfunction factors neuroprotective agents promotion remyelination immunological modifications may key targets novel treatment strategiespmid34006675 doi1011477 mf1416201785,1.0
seroconversion rate following hbv vaccination clinical practice role age dmt treatment mult scler relat disord 2021 feb 23 50102859 doi 101016 jmsard2021102859 online ahead printabstracthbv screening immunization recommended ms patients mandatory start dmt however studies evaluating immune response hbv vaccine ms patients scarce aimed evaluate seroprotection rate following hbv immunization ms patients assess older age dmttreatment influenced seroprotection conducted cohort study 2016 2020 compared immune response hbv vaccine ms patients different dmts patients 50 years old younger older 50 found patients noninjectable dmt presented lower rates seroprotection comparing patients injectable dmts without treatment patients older 50 although seroprotection rate similar remaining patients antibody antihbv surface antigen titers following hbv immunization lower patients likely require 4th dose vaccine achieve seroprotection findings highlight need consider hbv immunization ms patients early disease course order ensure proper immune response vaccinepmid33652232 doi101016 jmsard2021102859,0.0
assessing values circulating immune complexes multiple sclerosis patients following immunomodulator corticosteroid treatment exp ther med 2021 may 21 5 542 doi 103892 etm20219974 epub 2021 mar 23abstractmultiple sclerosis defined immunemediated disease affects central nervous system also characterized presence immune cells mediators contribute subsidiary neuroinflammation associated multiple sclerosis throughout evolution multiple sclerosis observed circulating immune complexes cics higher values patients especially acute phase disease thus aim present study observe acute attack relapsingremitting multiple sclerosis patients still present high values cics treatment glatiramer prednisone divided 70 patients multiple sclerosis high values cics two treatment groups one treated glatiramer copaxone immunomodulatory treatment prednisone corticosteroid treatment three months treatment assessed levels cics two multiple sclerosis groups observed patients followed immunomodulatory treatment lower values cics group followed corticosteroid treatment addition another observation established glatiramer treatment group higher levels vitamin d serum prednisone group multiple sclerosis patients conclude better outcomes point view results obtained comparative analysis values cics vitamin d demonstrated following immunomodulatory treatmentpmid33815615 pmcpmc8014965 doi103892 etm20219974,0.0
keeping ageing brain wired role purine signalling regulating cellular metabolism oligodendrocyte progenitors pflugers arch 2021 mar 13 doi 101007 s0042402102544z online ahead printabstractwhite matter wm highly prominent feature human cerebrum comprised bundles myelinated axons form connectome brain myelin formed oligodendrocytes essential rapid neuronal electrical communication underlies massive computing power human brain oligodendrocytes generated throughout life oligodendrocyte precursor cells opcs identified expression chondroitin sulphate proteoglycan ng2 cspg4 often termed ng2glia adult ng2+ opcs slowly proliferating cells stem celllike property selfrenewal differentiation pool late opcs differentiation committed opcs cops identified specific expression gproteincoupled receptor gpr17 capable differentiation myelinating oligodendrocytes adult brain reservoirs opcs cops ensure rapid myelination new neuronal connections formed response neuronal signalling underpins learning cognitive function however agerelated decline myelination associated loss neuronal function cognitive decline underlying causes myelin loss ageing manifold key factor decay opc stemness decline replenishment cops results ultimate failure myelin regeneration changes ageing opcs underpinned dysregulation neuronal signalling opc metabolic function highlight role purine signalling regulating opc selfrenewal potential importance gpr17 p2x7 receptor subtype agerelated changes opc metabolism moreover age main factor failure myelination chronic multiple sclerosis myelin loss alzheimers disease hence understanding importance purine signalling opc regeneration myelination critical developing new strategies promoting repair agedependent neuropathologypmid33712969 doi101007 s0042402102544z,1.0
relationship baff serum levels antinmdar autoantibodies fatigue patients systemic lupus erythematosus multiple sclerosis autoimmun rev 2021 mar 13102802 doi 101016 jautrev2021102802 online ahead printno abstractpmid33727153 doi101016 jautrev2021102802,0.0
current review next steps artificial intelligence multiple sclerosis risk research comput biol med 2021 mar 13 132104337 doi 101016 jcompbiomed2021104337 online ahead printabstractin last decades prevalence multiple sclerosis ms chronic inflammatory disease nervous system increased particularly northern european countries united states united kingdom promise artificial intelligence ai machine learning ml tools address problems ms research attracted increasing interest methods bayesian networks offer clear advantage since can integrate data causal knowledge allowing visualizing interactions dependent variables potential confounding factors review ai ml research methods applied ms found 216 papers using terms multiple sclerosis machine learning artificial intelligence bayes bayesian 90 relevant recently published half involve detection segmentation ms lesions quantitative analysis however clinical lifestyle risk factor assessment prediction largely ignored address risk factors provide association studies factors often fail include potential impact confounding factors bias especially causal explanations affect data interpretation reporting quality medical care access various countries address gaps literature propose causal bayesian network approach assessing risk factors ms can address deficiencies current epidemiological methods producing risk measurements makes better use observational datapmid33773193 doi101016 jcompbiomed2021104337,0.0
abnormal motor surround inhibition associated cortical deep grey matter involvement multiple sclerosis clin neurophysiol 2021 mar 12 132 5 11511156 doi 101016 jclinph202101029 online ahead printabstractobjective motor surround inhibition msi physiological mechanism contributes hand movement control focusing voluntary movement growing evidence suggests hand movement control impaired multiple sclerosis aim study evaluate msi ms investigate brain structures involved msi multiple sclerosismethods recruited 33 patients 23 controls investigate msi delivered transcranial magnetic single pulses index finger flexion motor evoked potentials recorded first dorsal interosseous active muscle abductor digiti minimi surround muscle msi expressed ratio motor evoked potentials recorded surround muscle movement rest participants underwent magnetic resonance studyresults patients impaired msi compared controls magnetic resonance showed basal ganglia smaller volumes higher mean diffusivity controls impaired msi correlated primary motor cortex basal ganglia involvement multiple sclerosisconclusion altered msi multiple sclerosis related cortical subcortical grey matter involvementsignificance study provides first demonstration pathophysiological mechanism underlying hand movement control dysfunction multiple sclerosis msi represents new therapeutic target multiple sclerosis rehabilitative approachespmid33774380 doi101016 jclinph202101029,0.0
covid19 vaccination patients multiple sclerosis learnt february 2021 mult scler 2021 apr 1513524585211003476 doi 101177 13524585211003476 online ahead printabstractbackground since vaccination coronavirus disease 2019 covid19 became available risks related vaccinating patients multiple sclerosis ms need carefully assessedobjective characterize safety occurrence immediate relapses following covid19 vaccination large cohort ms patientsmethods assessed safety bnt162b2 covid19 vaccination adult ms patientsresults 20 december 2020 25 january 2021 555 ms patients received first dose bnt162b2 vaccine 435 received second dose three cases covid19 infection encountered first dose safety profile covid19 vaccine characterized pain injection site fatigue headache increased risk relapse activity noted median followup 20 38 days first second vaccine doses respectively rate patients acute relapse 21 16 following first second doses respectively similar rate nonvaccinating patients corresponding period mild increase rate adverse events noted younger patients 1855 years among patients lower disability expanded disability status scale edss 30 patients treated immunomodulatory drugsconclusion covid19 bnt162b2 vaccine proved safe ms patients increased risk relapse activity notedpmid33856242 doi101177 13524585211003476,0.0
effect liraglutide insulin allergy patient glucocorticoidinduced diabetes multiple sclerosis nagoya j med sci 2021 may 83 2 343351 doi 1018999 nagjms832343abstractglucocorticoid use may trigger secondary diabetes exacerbate hyperglycemia patients diabetes mellitus dm liraglutide glucagonlike peptide1 glp1 receptor agonist used treatment patients type 2 diabetes reports mention liraglutide treatment steroidinduced dm sidm report patient sidm multiple sclerosis switching liraglutide combined metformin therapy improved glucose levels ameliorated symptoms insulin allergy liraglutide may useful treating sidm insulin allergypmid34239182 pmcpmc8236694 doi1018999 nagjms832343,0.0
hivnegative case talaromyces marneffei pulmonary infection tsc2 mutation j int med res 2021 may 49 5 3000605211016761 doi 101177 03000605211016761abstracttalaromyces marneffei rare dimorphic pathogenic fungus can induce severe infections human immunodeficiency virus hiv infected patients however infections also reported nonhiv hosts current case report describes rare case t marneffei pulmonary infection hivnegative patient mutation tuberous sclerosis complex subunit 2 tsc2 gene 24yearold male patient presented cough expectoration 6 months computed tomography showed multiple groundglass opacities cystic cavitated lesions lungs next generation sequencing ngs bronchoalveolar lavage fluid performed confirm t marneffei pulmonary infection results verified using bronchoscopy specimen cultures hivnegative patient without travel history endemic zones blood exon sequencing results showed mutation tsc2 gene date recovered well voriconazole therapy summary patients tsc2 mutations induce bronchopulmonary dysplasia may potential hosts t marneffei early timely diagnosis important improving prognosis ngs plays critical role diagnosis t marneffei pulmonary infectionpmid34057840 doi101177 03000605211016761,0.0
neuromyelitis optica spectrum disorder brain nerve 2021 may 73 5 475482 doi 1011477 mf1416201788abstractneuromyelitis optica spectrum disorder nmosd autoimmune disorder primarily associated optic neuritis myelitis area postrema syndrome several lines evidence suggest nmosd humoral immune disease mainly caused aquaporin4 antibody related complementdependent cytotoxicity astrocytes therefore nmosd distinct multiple sclerosis ms diagnosis nmosd recommended examine highsensitive cellbased assay targeting m23aqp4 always careful possibility false negative false positive result due assay prevent relapse disease best avoid diseasemodifying drugs used treatment ms possible acute exacerbation disease activity usually recommended start treatment administration oral steroids gradually move immunosuppressants however side effects treatments need evaluated currently additional options therapy biopharmaceutical agents eculizumab satralizumab rituximab inebilizumab prevent relapse disease new options can clearly exceed surpass usual treatments considered positively aggressive cases nmosdpmid34006678 doi1011477 mf1416201788,0.0
relapsingremitting multiple sclerosis brain nerve 2021 may 73 5 442449 doi 1011477 mf1416201784abstractmultiple sclerosis ms immunemediated inflammatory demyelinating disease central nervous system neither diagnostic tests markers ms causes must excluded thoroughly ms diagnosis considered definitive relapsingremitting type major clinical course ms diseasemodifying drugs dmds target clinical type many clinical studies demonstrated early intervention dmds may prevent disease progression transition relapsingremitting ms secondary progressive type windows opportunity dmds adequate dmd used appropriate patient optimal timepmid34006674 doi1011477 mf1416201784,1.0
perspectives urological care multiple sclerosis patients intractable rare dis res 2021 may 10 2 6274 doi 105582 irdr202101029abstractmultiple sclerosis ms chronic autoimmune disease central nervous system lower urinary tract dysfunction due ms includes dysfunction storage phase dysfunction voiding phase detrusorsphincter dyssynergia baseline evaluation includes voiding chart ultrasound scan urinary tract urine culture urodynamic study storage symptoms antimuscarinics firstline treatment clean intermittent catheterization cic indicated concomitant incomplete bladder emptying intradetrusor injections botulinum toxin btxa recommended refractory cases urinary diversion rarely indicated patients voiding symptoms cic alphablockers usually offered sexual dysfunction patients ms multifactorial phosphodiesterase type 5 inhibitors firstline therapies msassociated erectile dysfunction male female patients review summarizes epidemiology pathogenesis risk factors genetic clinical manifestations diagnostic tests management ms lastly urologic outcomes therapies reviewedpmid33996350 pmcpmc8122310 doi105582 irdr202101029,0.0
misdiagnosis multiple sclerosis time action mult scler 2021 may 27 6 805806 doi 101177 13524585211005367no abstractpmid33949226 doi101177 13524585211005367,0.0
cortical activity gait parameter characteristics people multiple sclerosis unobstructed gait obstacle avoidance gait posture 2021 mar 20 86226232 doi 101016 jgaitpost202103026 online ahead printabstractbackground people multiple sclerosis pwms present higher cortical activity walking however cortical activity gait avoiding obstacle still clearobjective investigate cortical activity gait spatialtemporal parameters pwms two different gait tasks ie unobstructed obstacle avoidance method fifteen pwms 15 healthy controls cg recruited participants performed ten trials gait condition wearing 64electrode cap electroencephalogram eeg 1024 hz kinematic data obtained 10 vicon cameras 200 hz eeg analyzed four cortical areas frontal motor parietal occipital cortex areas five frequency bands delta theta alpha beta gamma obtained power spectral density addition spatialtemporal gait parameters eg step length velocity measured twoway anova group x gait condition manova group x gait condition used compare gait eeg parameters respectively oneway anova used compare groups crossing phase obstacle avoidance conditionresults pwms presented lower step length velocity higher cortical activity frontal beta gamma parietal gamma cortical areas gait conditions compared cg moreover pwms presented increased cortical activation frontal parietal decreased step length velocity obstacle avoidance compared unobstructed gait addition pwms required cortical resources frontal parietal cg accomplish gait conditions obstacle avoidance task observed pwms positioned feet closer obstacle task compared cgconclusion pwms demand higher cortical resources accomplish gait tasks mainly necessary negotiate obstacle pathway higher cortical activity may compensatory mechanism deal damage subcortical structures caused multiple sclerosispmid33773240 doi101016 jgaitpost202103026,0.0
genetic variation wnt9b increases relapse hazard multiple sclerosis ann neurol 2021 mar 11 doi 101002 ana26061 online ahead printabstractobjective many multiple sclerosis ms genetic susceptibility variants identified understanding disease heterogeneity remains key challenge relapses core feature ms common primary outcome clinical trials prevention relapses benefiting patients immediately potentially limiting longterm disability accrual aim identify genetic variation associated relapse hazard ms analyzing largest study population datemethods performed genomewide association study gwas discovery cohort investigated genomewide significant variants replication cohort combining cohorts captured total 2231 relapses occurring start immunomodulatory treatment 991 patients assessing time relapse applied survival analysis utilizing cox proportional hazards models also investigated association ms genetic risk scores relapse hazard performed gene ontology pathway analysisresults lowfrequency genetic variant rs11871306 within wnt9b reached genomewide significance predicting relapse hazard replicated metaanalysis hazard ratio hr 215 95 confidence interval ci 170278 p 207 1010 pathway analysis identified association pathway response vitamin d relapse hazard p 433 106 ms genetic risk scores however associated relapse hazardinterpretation genetic factors underlying disease heterogeneity differ variants associated ms susceptibility findings imply genetic variation within wnt signaling vitamin d pathways contributes differences relapse occurrence present study highlights crosstalking pathways potential modulators ms disease activity article protected copyright rights reservedpmid33704824 doi101002 ana26061,0.0
mri findings blinded trials available treating physicians yes mult scler 2021 mar 291352458520984744 doi 101177 1352458520984744 online ahead printno abstractpmid33779365 doi101177 1352458520984744,0.0
clinicoradiological features amyotrophic lateral sclerosis patients olfactory dysfunction amyotroph lateral scler frontotemporal degener 2021 may 22 34 260266 doi 101080 2167842120201859544abstractobjective amyotrophic lateral sclerosis als adultonset neurodegenerative disorder characterized motor neuron involvement although olfactory dysfunction described als clinicoradiological features associated olfactory dysfunction remain poorly understood methods enrolled 30 patients als age sexmatched 53 healthy controls hcs participants underwent odor stick identification test japanese ositj clinical assessments including disease duration alsfrsr site onset forced vital capacity cognitive examinations reflected general executive memory language function investigated associations ositj score clinical features examined atrophic changes voxelbased morphometry vbm analysis mri results ositj score significantly lower als patients hcs 69 32 vs 98 19 p 0001 als significant relationships ositj score age examination frontal assessment battery word fluencies digit span forward adasjcog recognition education disease type duration alsfrsr vc multiple regression analysis stepwise method showed adasjcog recognition substantially predicted ositj score vbm analysis age sex total intracranial volume adasjcog recognition covariates showed ositj scores substantially correlated atrophic changes left orbital cortex consisting gyrus rectus medial orbital gyrus right hippocampus als conclusion als patients show substantial olfactory dysfunction association orbital cortex hippocampus involvements olfactory examination useful marker screening frontotemporal alteration alspmid33908332 doi101080 2167842120201859544,0.0
serum glial fibrillary acidic protein neuromyelitis optica spectrum disorder biomarker ann neurol 2021 mar 16 doi 101002 ana26067 online ahead printabstractobjective blood tests monitor disease activity attack severity treatment impact neuromyelitis optica spectrum disorder nmosd developed study investigated relationship serum glial fibrillary acidic protein sgfap concentration nmosd activity assessed impact inebilizumab treatmentmethods nmomentum prospective multicenter doubleblind placebocontrolled randomized clinical trial adults nmosd sgfap levels measured singlemolecule arrays simoa 1260 serial attackrelated samples 215 nmomentum participants 92 aquaporin 4immunoglobulin gseropositive control samples healthy donors patients relapsingremitting multiple sclerosis results baseline 62 participants 29 exhibited high sgfap concentrations 170 pg ml 2 standard deviations healthy donor mean concentration likely experience adjudicated attack participants lower baseline concentrations hazard ratio 95 confidence interval 309 1661 p 0001 median interquartile range iqr concentrations increased within 1 week attack baseline 1684 12894497 pg ml attack 21601 302794550 pg ml p 00015 correlated attack severity median fold change baseline fc iqr minor attacks 106 0974 major attacks 3432 871075 p 0023 attackrelated increase sgfap occurred primarily placebotreated participants fc 202 44983 p 0001 observed inebilizumabtreated participants fc 11 08246 p 005 five participants 28 elevated baseline sgfap reported neurological symptoms leading nonadjudicated attack assessmentsinterpretation sgfap may serve biomarker nmosd activity attack risk treatment effects clinicaltrialsgov nct02200770 article protected copyright rights reservedpmid33724534 doi101002 ana26067,0.0
rhythmic interlimb coordination lower limbs multiple sclerosis auditory pacing three different frequencies gait posture 2021 apr 5 86334340 doi 101016 jgaitpost202104001 online ahead printabstractbackground multiple sclerosis ms demyelinating disorder central nervous system heterogeneous symptoms persons ms pwms show reduced walking capacity changes gait pattern unknown extent coordination deficits present pwms can measured seated lower leg interlimb coordination tasks extent related motor cognitive functionresearch question control interlimb coordination lower limbs characterized pwms compared healthy controls hc seated rhythmical coordination task relationship interlimb coordination motor cognitive functionmethods rhythmical interlimb coordination assessed single session 38 pwms 13 hc using seated rhythmical coordination task comprising antiphase flexionextension lower limbs metronomes 075 hz 100 hz 150 hz outcomes phase coordination index pci movement amplitude movement frequency correlations interlimb coordination motor cognitive function examinedresults pwms showed impaired walking capacity preserved cognitive function mixed model analysis revealed significant effect group metronome frequency pci attenuated variability generating knee antiphase flexionextension movements movement amplitude highest metronome frequency 100 hz pwms significant correlations found pci cognitive function performing task metronome frequencies 075 hz 150 hz well motor function 150 hzsignificance pwms higher variability interlimb coordination compared hc stable interlimb antiphase coordination mode performed 100 hz significant correlations support existence relationship information processing speed well walking impairment interlimb coordination cognitive motor control always needed interlimb coordination movements associations strongest deviant higher lower metronome rhythmspmid33845379 doi101016 jgaitpost202104001,1.0
exploratory study neurochemical effects lowintensity pulsed ultrasound brains mice med biol eng comput 2021 apr 21 doi 101007 s11517021023519 online ahead printabstractthere now relatively large body evidence suggesting relationship dysfunction myelin oligodendrocytes etiology several neuropsychiatric disorders including depression schizophrenia also suggesting ultrasound methods may alleviate symptoms depression applied lowintensity pulsed ultrasound lipus brains mice treated demyelinating drug cuprizone drug used basis rodent model relevant number psychiatric neurologic disorders including depression schizophrenia multiple sclerosis prior conducting studies mice preliminary studies carried effects lipus vitro neuronlike shsy5y cells primary glial cells subsequent studies mice female c57bl 6 mice restrained plastic tubes 20 min daily ultrasound transducer near end tube directly mouses head lipus used intensity 25 mw cm2 daily 22 days control mice mice undergoing daily repetitive restraint stress rrs behavioral neurochemical studies done mice brain tissue obtained studies vitro indicated lipus stimulation intensity 15 mw cm2 delivered 5 min daily 3 days enclosed sterile cell culture plate incubator increased viability shsy5y primary glial cells studies mice lipus elevated levels doublecortin marker neurogenesis cortex compared levels rrs mice caused trend elevation brain levels brainderived neurotrophic factor hippocampus relative control levels lipus also increased sucrose preference measure attenuation anhedonia common symptom several psychiatric disorders rrs model mice ability lipus administered daily rescue damaged myelin oligodendrocytes studied mice treated chronically cuprizone 35 days lipus increased cortex corpus callosum levels myelin basic protein protein marker mature oligodendrocytes neural glial antigen 2 protein marker oligodendrocyte precursor cells relative levels cuprizone + sham animals results exploratory study suggest future comprehensive timerelated studies lipus brain chemistry behavior related neuropsychiatric disorders warranted exploratory study neurochemical effects low intensity pulsed ultrasound brains mice upper part figure lipus device invitro cell experimental setup center image lipus generating box image upper left shows cell experiment setup image upper right shows zoomedin sketch cell experiment image lower left shows setup repetitive restraint stress rrs mouse image lower middle shows setup lipus treatment mouse image lower right shows zoomedin sketch lipus treatment mousepmid33881705 doi101007 s11517021023519,1.0
fingolimod pediatriconset multiple sclerosis neurol sci 2021 may 4 doi 101007 s1007202105294z online ahead printno abstractpmid33945033 doi101007 s1007202105294z,0.0
assessment management acute disseminated encephalomyelitis adem pediatric patient paediatr drugs 2021 apr 8 doi 101007 s40272021004417 online ahead printabstractacute disseminated encephalomyelitis adem inflammatory demyelinating disease central nervous system typically presents childhood associated encephalopathy multifocal brain lesions although adem thought postinfectious disorder etiology still poorly understood adem often monophasic disorder contrast demyelinating disorders multiple sclerosis neuromyelitis optica spectrum disorder increasing awareness understanding testing myelin oligodendrocyte glycoprotein antibodies disease now known cause pediatric adem also potential relapsing diagnostic evaluation adem involves neuroimaging laboratory studies exclude potential infectious inflammatory neoplastic genetic mimics adem acute treatment modalities include highdose intravenous corticosteroids therapeutic plasma exchange intravenous immunoglobulin longterm outcomes adem generally favorable children significant morbidity related severity acute illness manifest ongoing neurocognitive sequelae research related optimal management pediatric adem impact prognosis needed review summarizes current knowledge pathogenesis epidemiology clinical features diagnostic evaluation treatment approaches outcomes pediatric adempmid33830467 doi101007 s40272021004417,1.0
cost effectiveness budget impact siponimod compared interferon beta1a treatment adult patients secondary progressive multiple sclerosis active disease switzerland pharmacoeconomics 2021 apr 1 doi 101007 s40273021010238 online ahead printabstractobjective study aim evaluate cost effectiveness budget impact siponimod compared interferon beta1a adult patients secondary progressive multiple sclerosis spms active disease swiss health insurance perspectivemethods conducted analysis using markov cohort model cycle length 1 year lifelong time horizon discount rate 3 cost health outcomes used matchingadjusted indirect comparison estimate clinical outcomes using data expand randomised controlled trial siponimod vs placebo nordic spms randomised controlled trial interferon beta1a vs placebo basis estimates disability progression relapse outcomes used 6month confirmed disability progression results estimate disability progression basecase analysis calculated qualityadjusted lifeyears qalys based external study administered eq5d3l questionnaire european patients multiple sclerosis included costs swiss franc chf year 2020 drug acquisition administration adverse events disease management also performed budget impact analysis estimate cost first 3 years introducing siponimodresults base case siponimod resulted mean incremental costs chf 84 901 siponimod chf 567 838 interferon beta1a chf 482 937 mean incremental qalys 1591 siponimod 7495 interferon beta1a 5905 leading incremental costeffectiveness ratio chf 53 364 per qaly gained probabilistic sensitivity analysis probability cost effectiveness siponimod assuming willingnesstopay threshold chf 100 000 per qaly gained 90 siponimod projected result drug administration costs siponimod chf 23 817 856 first 3 years introduction accompanied large cost offsets drug acquisition multiple sclerosis drugs considering drug administration monitoring adverse event management costs estimated result additional healthcare costs switzerland chf 2 177 021conclusions basecase analysis found siponimod may cost effective treating swiss adult patients spms active disease results costeffectiveness analyses valid assumption efficacy siponimod comparators disability progression overall spms population active spms populationclinical trial identifier nct01665144 economic evaluation based expand trialpmid33791945 doi101007 s40273021010238,0.0
optical coherence tomography angiography helps distinguish multiple sclerosis aqp4iggseropositive neuromyelitis optica spectrum disorder brain behav 2021 mar 30e02125 doi 101002 brb32125 online ahead printabstractintroduction aim characterize optical coherence tomography oct angiography measures patients multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd evaluate disease discrimination capacitymethods patients ms n 83 aqp4iggseropositive nmosd n 91 without history optic neuritis together healthy controls n 34 imaged main outcome measures peripapillary retinal nerve fiber layer prnfl thickness macular ganglion cellinner plexiform layer gcipl thickness macular vessel density vd perfusion density pd superficial capillary plexus diagnostic accuracy assessed using area receiver operating characteristics curveresults compared patients ms nmosd significantly smaller average thickness prnfl gcipl 800 590 958 m versus 920 802 101 m p 001 680 560 810 m versus 745 642 810 m p 001 significantly smaller whole vd pd areas 156 126 170 mm1 versus 167 148 177 mm1 p 001 038 031 042 mm1 versus 040 037 043 mm1 p 01 combination structural parameters average thickness prnfl gcipl microvascular parameters temporalinner quadrant vd temporalinner nasalinferior nasalouter quadrant pd revealed good diagnostic capability discriminating nmosd msconclusions oct angiography reveals different structural microvascular retinal changes ms aqp4iggseropositive nmosd combined structural microvascular parameters might promising biomarkers disease diagnosispmid33784027 doi101002 brb32125,0.0
safety tolerability nabiximols oromucosal spray review realworld experience observational studies registries case reports expert rev neurother 2021 mar 22 doi 101080 1473717520211904896 online ahead printabstractintroduction nabiximols oromucosal spray cannabisbased medicine containing balanced ratio 9tetrahydrocannabinol cannabidiol approved widely addon therapy symptomatic relief spasticity persons multiple sclerosis ms safety data nabiximols derive use ms spasticity data available analgesia areaareas covered review compiles safety tolerability data published observational studies registry analyses case reports identified systematic searches nabiximols oromucosal spray investigated spasticity n 20 chronic noncancer pain n 4 aligning known safety profile nabiximols demonstrated randomised controlled trials common adverse events reported consistently across studies conducted clinical practice conditions dizziness fatigue somnolence serious adverse events sae rate nabiximols observational studies ms spasticity 31 137 4351 total 39 treatmentrelated saes reported 32 patients spasticity specified resolved treatmentrelated saes recorded studies patients receiving nabiximols painexpert opinion realworld experience nabiximols oromucosal spray treating spasticity chronic pain indicates overall well tolerated good safety profilepmid33749480 doi101080 1473717520211904896,0.0
association serum ccl20 levels pulmonary vascular involvement primary biliary cholangitis patients systemic sclerosis int j rheum dis 2021 mar 22 doi 101111 1756185x14103 online ahead printabstractaim systemic sclerosis ssc chronic autoimmune disease resulting vasculopathy fibrosis skin major internal organs especially interstitial lung disease pulmonary arterial hypertension leading causes mortality cc motif ligand 20 ccl20 known homeostatic inflammatory chemokine associated fibrosis angiogenesis constantly expressed organs involved ssc therefore investigated potential contribution ccl20 development sscmethod conducted crosssectional analyses 67 ssc patients 20 healthy controls recruited single center 9 years serum ccl20 levels measured enzymelinked immunosorbent assay statistical analyses performed mannwhitney u test kruskalwallis test followed dunns multiple comparison test fishers exact probability test spearmans rank correlation coefficientresults ssc patients significantly higher serum ccl20 levels healthy controls ssc patients serum ccl20 levels correlated inversely percentage predicated diffusion lung capacity carbon monoxide positively mean pulmonary artery pressure mpap addition ssc patients increased serum ccl20 levels antimitochondrial antibody m2 titer significantly elevated relative normal levels ssc patients asymptomatic primary biliary cholangitis pbc possessed higher serum ccl20 levels without importantly serum ccl20 levels associated positively mpap values pbc presence multivariate regression analysisconclusion serum ccl20 levels may involved development pulmonary vascular involvement leading pulmonary arterial hypertension asymptomatic pbc ssc patientspmid33750014 doi101111 1756185x14103,0.0
longterm fingolimod treatment two pediatric patients multiple sclerosis neurol sci 2021 mar 10 doi 101007 s10072021051162 online ahead printabstractdata suggest patients pediatriconset multiple sclerosis poms initiate treatment diseasemodifying therapy early slow progression paradigms trial demonstrated oral fingolimod reduced annual rate relapse 82 compared intramuscular interferon beta1a children poms paradigms study followup 2 years data available safety efficacy fingolimod longer periods children poms present two cases children poms achieved sustained clinical benefit treatment fingolimod 2 years first patient 11yearold male participate paradigms study treatment nave time fingolimod initiation clinical condition remained stable 5 years treatment relapses radiological lesion progression second patient female initiated fingolimod age 12 years 2 years poms diagnosis 8month trial interferon beta1a patient experienced two relapses interferon beta1a relapses 2 years treatment fingolimod mri scans showed new active lesions data show prolonged treatment fingolimod can safe effective longterm treatment first secondline therapy children pomspmid33751260 doi101007 s10072021051162,0.0
therapeutic recommendations seasonal influenza vaccine multiple sclerosis patients treatment ocrelizumab expert consensus j neurol 2021 feb 20 doi 101007 s00415021104660 online ahead printno abstractpmid33609155 doi101007 s00415021104660,0.0
generation six induced pluripotent stem cell lines patients amyotrophic lateral sclerosis associated genetic mutations either fus anxa11 stem cell res 2021 feb 12 52102246 doi 101016 jscr2021102246 online ahead printabstractamyotrophic lateral sclerosis als characterized degeneration upper lower motor neurons causing gradual paralysis resulting death 35 years diagnosis als causative mutations identified multiple genes including fused sarcoma fus recently characterized annexin a11 anxa11 derived induced pluripotent stem cell ipsc lines six als patient lymphoblastoid cell lines three mutations fus q519e r521h r522g three mutations anxa11 g38r d40g r235q lines characterized provide novel resource investigation als pathologypmid33610019 doi101016 jscr2021102246,0.0
sexual dimorphism immunometabolism autoimmunity impact personalized medicine autoimmun rev 2021 feb 17102775 doi 101016 jautrev2021102775 online ahead printabstractimmune cells play essential roles metabolic homeostasis thus undergo analogous changes normal physiology eg puberty pregnancy various metabolic immune diseases essential component close relationship two sex differences many autoimmune diseases systemic lupus erythematous multiple sclerosis feature strikingly increased prevalence females whereas contrast infectious diseases ebola middle east respiratory syndrome affect men women therefore fundamental aspects metabolic homeostasis immune functions regulated differently males females can observed sex hormoneimmune interaction androgens testosterone shown immunosuppressive effects whilst estrogen opposite side spectrum immunoenhancing facilitation mechanisms addition two sexes exhibit significant differences metabolic regulation estrous cycles females known induce variability traits pronounced metabolic disease phenotype exhibited males likely differences underlie development metabolic autoimmune diseases response current treatment options sexual dimorphism immunometabolism emerged become area intense research aiming uncover sexbiased effector molecules various metabolic tissues immune cell types identify sexbiased celltypespecific functions common effector molecules understand whether sex differences metabolic immune functions influence autoimmune pathogenesis review will summarize recent findings address critical questions sexual dimorphism immunometabolism well translational implications clinical management autoimmune diseasespmid33609790 doi101016 jautrev2021102775,0.0
triad tdp43 control neurodegeneration autoregulation localization aggregation nat rev neurosci 2021 mar 2 doi 101038 s41583021004311 online ahead printabstractcytoplasmic aggregation tar dnabinding protein 43 tdp43 also known tardbp tdp43 key pathological feature several neurodegenerative diseases including amyotrophic lateral sclerosis als frontotemporal dementia ftd tdp43 typically resides nucleus can shuttle nucleus cytoplasm exert multiple functions include regulation splicing trafficking stabilization rna cytoplasmic mislocalization nuclear loss tdp43 associated als ftd suggesting calibrated levels correct localization tdp43 achieved autoregulatory loop tightly controlled nucleocytoplasmic transport safeguard normal function furthermore tdp43 can undergo phase transitions including dispersion liquid droplets accumulation irreversible cytoplasmic aggregates thus autoregulation nucleocytoplasmic transport phase transition part intrinsic control system regulating physiological levels localization tdp43 together essential cellular homeostasis affected neurodegenerative diseasepmid33654312 doi101038 s41583021004311,0.0
correction selective immunomodulatory neuroprotective effects nod2 receptor agonist mouse models multiple sclerosis neurotherapeutics 2021 apr 27 doi 101007 s13311021010354 online ahead printno abstractpmid33907979 doi101007 s13311021010354,1.0
efficacy classification modern therapies multiple sclerosis j comp eff res 2021 feb 23 doi 102217 cer20200267 online ahead printabstractbackground association british neurologists abn 2015 guidelines suggested classifying multiple sclerosis therapies according average relapse reduction sought classify newer therapies cladribine ocrelizumab ofatumumab ozanimod based guidelines materials methods therapies classified using direct comparative trial results per abn guidelines generating classification probabilities therapy based comparisons versus placebo network metaanalysis annualized relapse rate results approaches cladribine ofatumumab classified high efficacy ocrelizumab ozanimod 10 mg classified moderate high efficacy depending approach used conclusion cladribine ofatumumab efficacy comparable therapies classified abn guidelines high efficacypmid33620251 doi102217 cer20200267,0.0
selected clostridia strains human microbiota metabolite butyrate improve experimental autoimmune encephalomyelitis neurotherapeutics 2021 apr 7 doi 101007 s13311021010167 online ahead printabstractgut microbiome studies multiple sclerosis ms patients unravelling consistent modest patterns gut dysbiosis among significant decrease clostridia cluster iv xiva reported present study investigated therapeutic effect previously selected mixture human gutderived 17 clostridia strains belong clostridia clusters iv xiva xviii clinical outcome experimental autoimmune encephalomyelitis eae observed clinical improvement related lower demyelination astrocyte reactivity well tendency lower microglia reactivity infiltrating macrophages axonal damage central nervous system cns enhanced immunoregulatory response regulatory t cells periphery transcriptome studies also highlighted increased antiinflammatory responses related interferon beta periphery lower immune responses cns since clostridiatreated mice found present higher levels immunomodulatory shortchain fatty acid scfa butyrate serum studied clinical effect reproduced butyrate administration alone eae experiments proved preventive slight therapeutic impact cns autoimmunity thus smaller therapeutic effect highlighted clostridiainduced clinical effect exclusively related scfa reproduced butyrate administration alone although still unknown clostridia strains will effect ms patients gut dysbiosis ms patients partially rebalanced commensal bacteria immunoregulatory properties beneficial effect ms clinical coursepmid33829410 doi101007 s13311021010167,1.0
can pulse steroid therapy increase risk infection covid19 patients multiple sclerosis clin neurol neurosurg 2021 feb 15 203106563 doi 101016 jclineuro2021106563 online ahead printabstractbackground iran one countries high prevalence multiple sclerosis ms covid19ms patients receiving immunomodulatory immunosuppressive therapy higher risk infection due significance determining risk factors getting covid19 among ms patients present study designed assess risk infection following pulse steroid therapymethods crosssectional study included ms patients received corticosteroids tehran december 2019 august 2020 covid19 pandemic spread subjects clinical records including sex age type ms type medication number days using corticosteroids status prednisolone intake number days receiving prednisolone corticosteroid therapy obtained moreover main outcomes covid19 infection occurrence death recorded patients visits followup phone calls covid19 infection confirmed physicians according clinical performance rtpcr chest ct scan antibody testsresults totally 133 ms cases participated study pulse therapy completed 104 782 patients 57 days 89 669 cases used prednisolone tablet following pulse therapy overall infection covid19 observed 8 6 cases among 5 714 cases received pulse therapy 57 days 4 571 cases history taking prednisolone tablet age less 40 years 103 95 ci 023451 male sex 035 95 ci 003334 rrms type 287 95 ci 0521572 effect risk covid19 infection addition statistically significant difference subjects shortterm pulse therapy duration 34 days 068 012374 longterm pulse therapy duration 57 days similarly statistically significant difference observed subjects taking prednisolone 162 034761 taking prednisolone furthermore significant association different medication groups risk covid19 infection p 005 death occurred due covid19 infection among subjectsconclusion covid19 infection common among female younger patients well patients longer duration pulse therapy prednisolone intake significant association pulse steroid therapy ms patients risk infection covid19 iranian populationpmid33631509 doi101016 jclineuro2021106563,0.0
circulating heparan sulfate proteoglycans biomarkers health disease semin thromb hemost 2021 apr 47 3 295307 doi 101055 s00411725063 epub 2021 apr 1abstractcellsurface heparan sulfate proteoglycans hspgs play key roles regulating cell behavior cell signaling cell matrix interactions physiological pathological conditions soluble forms glycocalyx shedding merely waste products rather bioactive molecules detectable serum may useful diagnostic prognostic markers addition case glypican3 hepatocellular carcinoma may specifically expressed pathological tissue representing promising targets immunotherapy primary goal comprehensive review critically survey main findings clinical data last 20 years provide readers overall picture diagnostic prognostic value circulating hspgs moreover issues related involvement hspgs various pathologies including cardiovascular disease thrombosis diabetes obesity kidney disease cancer trauma sepsis also multiple sclerosis preeclampsia pathologies requiring surgery pulmonary disease others will discussedpmid33794553 doi101055 s00411725063,0.0
brief report passive mechanical properties gastrocnemius multiple sclerosis ankle contracture clin biomech bristol avon 2021 mar 23 84105338 doi 101016 jclinbiomech2021105338 online ahead printabstractbackground ankle contracture common people multiple sclerosis ms mechanisms contracture clear study aimed identify mechanisms contracture ms comparing passive muscle length stiffness known tension separated contributions muscle fascicles tendons people ms contracture healthy peoplemethods passive lengthtension curves gastrocnemius muscletendon unit derived passive ankle torque angle using published biomechanical method ultrasound images medial gastrocnemius muscle fascicles used partition lengthtension curves fascicle tendon components lengths stiffness muscletendon unit muscle fascicles tendons compared groups linear regressionfindings data obtained 15 participants ms contracture age 53 12 years mean sd 25 healthy participants 48 20 years participants ms clinically significant ankle contracture shorter fascicles slack length betweengroups mean difference 08 cm 95 ci 12 04 cm p 0001 100 n 07 cm 95 ci 13 01 cm p 002 compared healthy participants differences groups outcomesinterpretation tensionreferenced comparisons passive muscle length stiffness show people ms contracture shorter fascicles low high tension compared healthy people changes muscletendon unit tendon studies needed identify causes mechanisms contracture neurological conditionspmid33812198 doi101016 jclinbiomech2021105338,0.0
kidney imaging surveillance commercially insured patients tuberous sclerosis complex pediatr neurol 2020 dec 26 1172126 doi 101016 jpediatrneurol202012008 online ahead printabstractbackground kidney disease historically primary source early mortality adults tuberous sclerosis complex tsc kidney imaging surveillance promotes early detection lesions requiring intervention describe kidney imaging frequency relationship patientlevel characteristics commercially insured patients tsc united statesmethods retrospective observational study used 2003 2016 enrollment claims data deidentified fully insured commercial health insurer patients tsc less 65 years included patientlevel kidney imaging rate calculated number kidney imaging procedures divided length continuous enrollment multiple linear regression model used determine relationship imaging rate progression tscassociated kidney disease number specialists seen nephrologist careresults least half 70 patients tsc included study aged 16 years younger followup period 14 years median kidney imaging rate 013 procedures per year 43 n 30 patients lacking evidence kidney imaging observation period imaging frequency increased progression tscassociated kidney disease specialists nephrologist care p 005 three regression model conclusions substantial percentage patients tsc united states risk delayed detection kidney manifestations due infrequent kidney imaging surveillance multispecialty care including neurologists may positively affect kidney surveillance ratespmid33647778 doi101016 jpediatrneurol202012008,0.0
identification posterior visual pathway lesions mri burden people multiple sclerosis neurosciences riyadh 2021 apr 26 2 120127 doi 1017712 nsj2021220200048abstractobjectives review systematically identifies posterior visual pathway lesions mri burden people multiple sclerosis ms methods articles searched web science medline embase databases january 2020 english language articles 2000 2019results review presents summary measures related mri assessment overall measure ms visual pathway lesions total 44 articles fulfilled inclusion criteria covering period 20002019 different atypical outcomes reveal low risk subsequent clinically predefined ms development specifically presence normal brain mri several impairments related quality life identified result effect retinal nerve fiber layer ganglion cell layer inner plexiform layerconclusion afferent visual system ms offers unique accessibility structurerelated functions understanding offered electrophysiology considering vision useful framework examining new multiple sclerosis therapiespmid33814364 doi1017712 nsj2021220200048,0.0
joint segmentation multiple sclerosis lesions brain anatomy mri scans contrast resolution cnns proc ieee int symp biomed imaging 2021 apr 202119711974 doi 101109 isbi4821120219434127 epub 2021 may 25abstractwe present first deep learning method segment multiple sclerosis lesions brain structures mri scans possibly multimodal contrast resolution method requires segmentations trained images leverages generative model bayesian segmentation generate synthetic scans simulated lesions used train cnn method can retrained segment resolution adjusting amount synthesised partial volume construction synthetic scans perfectly aligned labels enables training noisy labels obtained automatic methods training data generated fly aggressive augmentation including artefacts applied improved generalisation demonstrate method two public datasets comparing stateoftheart bayesian approach implemented freesurfer dataset specific cnns trained real data code available https githubcom bbillot synthsegpmid34367472 pmcpmc8340983 doi101109 isbi4821120219434127,0.0
benign monomelic amyotrophy lower limb cohort chinese patients brain behav 2021 mar 2e02073 doi 101002 brb32073 online ahead printabstractbackground benign monomelic amyotrophy lower limb bmall neurogenic syndrome representing unclear field studies might helpful elucidate uncertainties regarding causation outcome risk progression amyotrophic lateral sclerosis als methods according inclusion exclusion criteria 37 patients bmall retrospectively collected three neuromuscular centers january 2012 october 2018 detailed medical data summarized multiple laboratory tests examined routine electrophysiological examinations muscle mri lower limbs muscle biopsy conductedresults cohort included 24 male 13 female cases median age onset 47 years muscle mri revealed distribution involved muscles matched extent fat infiltration pattern muscle atrophy can divided following four types six patients thigh atrophy type 14 patients leg atrophy type ii 10 patients disproportionate atrophy thigh leg type iii seven patients wellproportionate atrophy thigh leg type iv electrophysiological findings showed neurogenic pattern spontaneous activity abnormal h reflex suggested disorder spinal anterior horn cell patients types iiii however electrophysiological abnormalities found patients type iv muscle pathology varied almost normal pattern advanced neurogenic pattern nine biopsied patients followup showed two patients type ii developed als four years later patients type iv stable condition without complaintsconclusion muscle mri useful exactly localize distribution involved muscles bmall patients distribution atrophic muscles can roughly divided four types based mri features classification distributing types might indicator prognosis bmallpmid33650811 doi101002 brb32073,0.0
b lymphocytes gastrointestinal tract autoimmunity autoimmun rev 2021 feb 17102777 doi 101016 jautrev2021102777 online ahead printabstractunder homeostatic conditions bidirectional interactions gastrointestinal immune system allow production inflammatory antiinflammatory responses designed prevent undesirable inflammation respond efficiently potential insults balanced regulation can disrupted disorders affect tissues remote gastrointestinal tract seen autoimmune diseases recent reports described variety b lymphocytemediated functions likely contribute gastrointestinal homeostasis greater extent previously thought studies shown early b cell development takes place within intestine selfreactive b cells rendered tolerant using mechanisms known occur bone marrow indicating gastrointestinal tract contributes maintaining immune tolerance self relatedly continuous bacterial stimulation essential maintaining regulatory b cell functions mediating mucosal homeostasis studies neuroinflammation intestinal iga+ b cells constitute prominent source lymphocytes organism can migrate inflamed tissues exert regulatory functions attenuate inflammation central nervous system indicating addition local effects intestin gut microbiotab cell crosstalk can exert longrange beneficial effects translational level metabolites produced gut microbiota can act b cellintrinsic epigenetic modulators reducing inflammation skin kidneys mice suffering experimental lupus given significant impact b cellintestinal microbiota interactions momentum improving understanding pathways autoinflammatory diseases designing novel therapeutic strategies systemic autoimmune diseases b cells play key rolespmid33609796 doi101016 jautrev2021102777,0.0
reelin depletion protects atherosclerosis decreasing vascular adhesion leukocytes arterioscler thromb vasc biol 2021 feb 25atvbaha121316000 doi 101161 atvbaha121316000 online ahead printabstractobjective reelin receptor apoer2 apolipoprotein e receptor 2 play prominent role endothelial cell dysfunction promoting leukocyteendothelial cell adhesion important component inflammatory process underlying atherosclerosis therefore hypothesized pharmacological depletion circulating reelin represents novel therapeutic strategy impede progression atherosclerosis approach results vitro studies demonstrated human plasma induced monocyte adhesion endothelial cells reelindepleted plasma effect monocyte adhesion signaling analysis revealed reelin activated dab2 pi3k akt nfb nuclear factor b cascade promote expression adhesion markers eselectin icam1 intercellular adhesion molecule 1 vcam1 vascular cell adhesion molecule 1 intravital microscopy confirmed decreased leukocyteendothelial adhesion mice treated reelin antisense oligonucleotide vascular smooth muscle cells reelin induced stat3 phosphorylation promote cell proliferation another hallmark atherosclerotic plaque progression investigate reelin pharmaceutical depletion protects atherosclerosis lowdensity lipoprotein receptordeficient ldlr mice fed highcholesterol diet treated either reelin antisense oligonucleotide neutralizing antibody cr50 systemically deplete circulating reelin treatments atherosclerotic plaque progression markedly attenuated vivo results suggest reelin depletion decreases vascular adhesion inhibits recruitment monocytes consequently prevents plaque progressionconclusions findings suggest reelin inhibition may provide novel therapeutic approach counteract leukocyte monocyte adhesion well extravasation inhibit progression atherosclerosis strategy may also relevant diseases involve leukocyte monocyte extravasation central pathological mechanism multiple sclerosis arthritispmid33626909 doi101161 atvbaha121316000,0.0
nacetyllysyltyrosylcysteine amide novel systems pharmacology agent reduces bronchopulmonary dysplasia hyperoxic neonatal rat pups free radic biol med 2021 feb 16s08915849 21 000794 doi 101016 jfreeradbiomed202102006 online ahead printabstractbronchopulmonary dysplasia bpd caused primarily oxidative stress inflammation induce bpd neonatal rat pups raised hyperoxic 90 o2 environments day one p1 day ten p10 treated nacetyllysyltyrosylcysteine amide kyc vivo studies showed kyc improved lung complexity reduced myeloperoxidase mpo positive + myeloid cell counts mpo protein chlorotyrosine formation increased endothelial cell cd31 expression decreased 8ohdg cox1 cox2 hmgb1 rage tlr4 increased weight gain improved survival hyperoxic pups epr studies confirmed mpo reaction mixtures oxidized kyc kyc thiyl radical adding recombinant hmgb1 mpo reaction mixture containing kyc resulted kyc thiylation hmgb1 rat lung microvascular endothelial cell rlmvec cultures kyc thiylation rlmvec proteins increased rlmvec cultures treated mpo+h2o2 followed h2o2 kyc alone kyc treatment hyperoxic pups decreased total hmgb1 lung lysates increased kyc thiylation hmgb1 terminal hmgb1 thiol oxidation decreased hmgb1 association tlr4 rage shifted hmgb1 lung lysates nonacetylated lysylacetylated isoform suggesting kyc reduced lung cell death recruited immune cells become primary source hmgb1 released hyperoxic lungs mpodependent independent kycthiylation keap1 increased rlmvec cultures treating hyperoxic pups kyc increased kyc thiylation sglutathionylation keap1 nrf2 activation data suggest kyc novel system pharmacological agent exploits mpo inhibit toxic oxidant production oxidized thiyl radical inactivates hmgb1 activates nrf2 increases antioxidant enzyme expression improve lung complexity reduce bpd hyperoxic rat pupspmid33607217 doi101016 jfreeradbiomed202102006,0.0
metformin protects myelin degeneration mouse model iysophosphatidylcholineinduced demyelination optic chiasm cell j 2021 apr 23 1 119128 doi 1022074 cellj20217174 epub 2021 mar 1abstractobjective multiple sclerosis ms demyelinating disease central nervous system autoimmune pathology longterm inflammation lead substantial demyelination events lead substantial loss oligodendrocytes ols longer period results axonal loss longterm disabilities neural cells protection approaches decelerate inhibit disease progress avoid disability previous studies showed metformin beneficial effects neurodegenerative conditions study examined possible protective effects metformin toxininduced myelin destruction adult mice brainsmaterials methods experimental study lysophosphatidylcholine lpc used induce demyelination mice optic chiasm examined extent demyelination different time points post lpc injection using myelin staining evaluated severity inflammation functional state optic pathway evaluated visual evoked potential vep recordingresults metformin attenuated lpcinduced demyelination p005 inflammation p005 protected significant decrease p005 functional conductivity optic tract data indicated metformin administration attenuates myelin degeneration following lpc injection led functional enhancementconclusion findings suggest metformin combination therapy patients suffering myelin degenerative diseases especially multiple sclerosis however additional mechanistic studies requiredpmid33650828 doi1022074 cellj20217174,1.0
multiple ways dead end diverse mechanisms als mutant genes induce cell death cell cycle 2021 mar 15116 doi 101080 1538410120211886661 online ahead printabstractamyotrophic lateral sclerosis als deadly neuromuscular disorder caused progressive motor neuron loss brain spinal cord past decades number genetic mutations identified cause associated als disease progression numerous genes harbor als mutations encode proteins displaying wide range physiological functions limited overlap despite divergent functions mutations genes typically trigger protein aggregation can confer gain lossoffunction number essential cellular processes nuclear processes mrna splicing response dna damage significantly affected als patients cytoplasmic organelles mitochondria damaged als mutant proteins processes maintain cellular homeostasis autophagy nonsensemediated mrna decay nucleocytoplasmic transport also impaired als mutations review multiple mechanisms mutations major alsassociated genes tardbp c9orf72 fus lead impairment essential cellular processespmid33722167 doi101080 1538410120211886661,0.0
effect fampridine gait people multiple sclerosis ms laeknabladid 2021 apr 107 4 179184 doi 1017992 lbl202104630abstractintroduction fampridine drug people multiple sclerosis ms broadspectrum voltagedependent potassium channel blocker enhances synaptic transmission drug shown able enhance conduction demyelinated axons thereby leading improved gait patients ms purpose study examine effect fampridine gait function people ms end 2 weeks trial drug period observe many patients continued drug therapymaterial methods data 41 individuals ms collected retrospectively study measurements administered physiotherapists results timed 25foot walk t25fw 12item multiple sclerosis walking scale msws12 obtained medical records national university hospital icelandresults results showed significant difference walking speed end trial period p00001 average improvement walking speed 22 results also demonstrated significant difference msws12 scores end treatment p00001 average improvement msws12 114 points eighteen individuals 439 continued treatment trial periodconclusion fampridine can positive effect impaired gait function people ms can important adjunct treatmentpmid33769308 doi1017992 lbl202104630,1.0
elevated cerebrospinal fluid 2microglobulin levels patients neuromyelitis optica spectrum disorders mult scler relat disord 2021 jan 19 49102774 doi 101016 jmsard2021102774 online ahead printabstractcerebrospinal fluid csf 2microglobulin 2mg levels elevated patients multiple sclerosis ms examined levels 2mg serum cerebrospinal fluid csf 46 patients neuromyelitis optica spectrum disorders nmosd serum 21 healthy controls hc csf 25 disease controls noninflammatory neurological diseases nind normal csf results csf 2mg levels significantly higher patients nmosd controls weak association number white blood cells protein lactate levels csf csf 2mg thus one nonspecific indicator inflammation nmosdpmid33713918 doi101016 jmsard2021102774,0.0
use standardization interpretation brain imaging data clinical trials neurodegenerative disorders neurotherapeutics 2021 apr 12 doi 101007 s13311021010274 online ahead printabstractimaging biomarkers play wideranging role clinical trials neurological disorders includes selecting appropriate trial participants establishing target engagement mechanismrelated pharmacodynamic effect monitoring safety providing evidence disease modification early stages clinical drug development evidence target engagement downstream pharmacodynamic effectespecially clear relationship dosecan provide confidence therapeutic candidate advanced larger expensive trials can inform selection dose s tested ie derisk drug development program laterphase trials evidence therapeutic candidate altering diseaserelated biomarkers can provide important evidence clinical benefit compound observed grounded meaningful biological changes interpretation diseaserelated imaging markers comparability across different trials imaging tools greatly improved standardized outcome measures defined standardization impinge scientific advances imaging tools per se provides common language results generated tools expressed pet markers pathological protein aggregates structural imaging brain atrophy common diseaserelated elements across many neurological disorders however pet tracers pathologies beyond amyloid tau needed interpretability structural imaging can enhanced simple considerations guard possible confound pseudoatrophy learnings muchstudied conditions alzheimers disease multiple sclerosis will beneficial field embraces rarer diseasespmid33846962 doi101007 s13311021010274,0.0
neuromyelitis optica neuromyelitis optica spectrum disorder clinical syndrome diagnistic classification nervenarzt 2021 mar 16 doi 101007 s0011502101098w online ahead printabstractneuromyelitis optica spectrum disorder nmosd derived nmo devics disease considered distinct disease since discovery novel pathogenic serum autoantibody targeting aquaporin4 aqp4igg distinguished classical multiple sclerosis ms continuous extension knowledge clinical manifestations previously narrow diagnostic term nmo became nmosd also used diagnostic criteria since 2015 current diagnostic criteria enable early diagnosis nmosd patients without aqp4igg typical clinical manifestations include involvement spinal cord optic nerve brainstem typically patients disease also present neuropathic pain painful tonic spasms also unusual manifestations nmosd especially aqp4igg positive nmosd patients coexistence autoimmune diseases frequently observed cases nmosd follows relapsing course exacerbationfree periods sometimes lasting years can manifested first advanced adulthood subset aqp4igg negative nmosd patients found harbor autoantibodies targeting myelin oligodendrocyte glycoprotein mog considered distinct disease entity mog antibodyassociated disorders mogad can present clinical syndromes resembling nmosd ms currently subject intensive researchpmid33728474 doi101007 s0011502101098w,1.0
exploring roles tryptophan metabolism ms beyond neuroinflammation neurodegeneration paradigm shift neuropsychiatric symptoms brain behav immun health 2021 jan 4 12100201 doi 101016 jbbih2021100201 ecollection 2021 marabstractthe metabolism tryptophan kynurenine pathway kp increasingly recognised contributing disease progression autoimmune inflammatory disease multiple sclerosis ms review roles inflammation kp recontextualised better understand aetiology neuropsychiatric symptoms depression postpartum depression suicidality fatigue cognitive dysfunction ms symptoms will discussed context cytokineinduced sickness behaviours kp activation levels neurotoxicity neuroprotection ms particular will emphasis neuropsychiatric symptoms ms occur shared background inflammation kp dysregulation discourse review aims promote future research elucidating kp mechanisms ms inevitably lead targeted treatment options neuropsychiatric symptoms disease progressionpmid34589733 pmcpmc8474511 doi101016 jbbih2021100201,0.0
illuminating vitro effects epsteinbarr virus vitamin d immune response multiple sclerosis patients j neurovirol 2021 mar 5 doi 101007 s13365021009517 online ahead printabstractgiven complexity immune complex diseases including multiple sclerosis ms plausible interactions different risk factors delineating interplay imperative current study aimed evaluate vitro effects epsteinbarr virus ebv vitamin d immune response ms patients healthy controls status vitamin d ebv load evaluated using multiple techniques vitro ebvinfected peripheral blood mononuclear cells pbmcs presence absence vitamin d checked il10 ifn vitamin d receptor ms patients showed significantly higher plasma levels 1 25 oh 2d 25ohd increased ebv load lower levels vitamin d receptor vdr expression compared healthy controls interestingly inverse correlation observed vdr expression ebv load pbmcs indeed levels ifn il10 production significantly higher supernatant collected vitro ebvinfected pbmcs ms patients compared controls vitamin dtreated pbmcs showed reduced levels ifn production vitro treatment vitamin d showed influence il10 production ebv vitamin d found exert opposite vitro effects immune dysregulation patients results highlight complex interactions different risk factors immune systempmid33666884 doi101007 s13365021009517,0.0
reexamining effects highdose intravenous methylprednisolone secondary progressive multiple sclerosis neurodegener dis manag 2021 mar 11 doi 102217 nmt20200051 online ahead printabstractbackground objective intravenous methylprednisolone ivmp previously given secondary progressive multiple sclerosis spms patients study aimed reexamine effects ivmp spms materials methods major electronic databases searched randomized controlled trials results four randomized controlled trials included ivmp may inferior mitoxantrone mtx terms expanded disability status scale edss improvement significant difference terms edss reduction magnetic resonance imaging mri plaque reduction ivmp + mtx compared mtx significant difference ivmp cyclophosphamide based edss progression relapse reduction conclusion ivmp routinely used treatment spms recommended alternative treatment spmspmid33703936 doi102217 nmt20200051,0.0
animal modeling lower urinary tract dysfunction associated multiple sclerosis part justification mouse model ms research neurourol urodyn 2021 mar 14 doi 101002 nau24649 online ahead printabstractlower urinary tract symptoms dysfunction luts lutd contribute loss quality life morbidity need medical intervention patients multiple sclerosis ms although ms inflammatory neurodegenerative disease clinical manifestations including continence control disorders traditionally attributed loss neural signaling due neurodegeneration clinical approaches msluts lutd focused addressing symptoms context urodynamic dysfunctions pathophysiologic understandings incomplete mouse model provides useful research platform discovery detailed molecular cellular tissuelevel knowledge disease clinical manifestations aim twopart review provide stateoftheart update use mouse model ms research focus lower urinary tract symptoms part presents summary current understanding ms pathophysiology impact lower urinary tract symptoms briefly introduces types mouse models available study ms part ii presents common animal models currently available study ms mechanism relevance msluts lutd urinary pathophysiology advantages disadvantagespmid33719097 doi101002 nau24649,0.0
multiple sclerosis rituximab covid19 ann clin transl neurol 2021 mar 30 doi 101002 acn351342 online ahead printabstractwe conducted retrospective cohort study kaiser permanente southern california 1 january 2020 30 september 2020 found rituximabtreated persons multiple sclerosis pwms n 1895 likely hospitalized n 8 333 die n 0 covid19 compared 481 million nonms population 58 14 respectively time months adjusted 032 95 ci 015069 p 00033 receiving 1000 mg compared lower doses last infusion adjusted 628 95 ci 138285 p 00173 independent predictors covid19 severity rituximabtreated pwms counseled take extra precautions 5 months following infusion using extended dosing intervals lower doses consideredpmid33783140 doi101002 acn351342,0.0
part 2 mouse models multiple sclerosis research neurourol urodyn 2021 mar 19 doi 101002 nau24654 online ahead printabstractlower urinary tract symptoms dysfunction luts lutd contribute loss quality life morbidity need medical intervention patients multiple sclerosis ms although ms inflammatory neurodegenerative disease clinical manifestations including continence control disorders traditionally attributed loss neural signaling due neurodegeneration clinical approaches msluts lutd focused addressing symptoms context urodynamic dysfunctions pathophysiologic understandings incomplete mouse model provides useful research platform discovery detailed molecular cellular tissuelevel knowledge disease clinical manifestations aim twopart review provide stateoftheart update use mouse model ms research focus lower urinary tract symptoms part presents summary current understanding ms pathophysiology impact lower urinary tract symptoms briefly introduces types mouse models available study ms part ii presents common animal models currently available study ms mechanism relevance msluts lutd urinary pathophysiology advantages disadvantagespmid33739481 doi101002 nau24654,0.0
exit strategies natalizumabtreated rrms high risk progressive multifocal leukoencephalopathy multicentre comparison study neurotherapeutics 2021 apr 12 doi 101007 s13311021010372 online ahead printabstractthe main aim study evaluate efficacy safety profile ocrelizumab ocr rituximab rtx cladribine cla employed natalizumab ntz exit strategies relapsingremitting multiple sclerosis rrms patients highrisk progressive multifocal leukoencephalopathy pml multicentre retrospective realworld study consecutive rrms patients eleven tertiary italian ms centres switched ntz ocr rtx cla january 1st 2019 december 31st 2019 primary study outcomes annualized relapse rate arr magnetic resonance imaging mri outcome treatment effects estimated inverse probability treatment weighting iptw based propensityscore ps approach additional endpoint included confirmed disability progression cdp measured expanded disability status scale adverse events aes patients satisfying predefined inclusion exclusion criteria 120 64 switched ocr 36 rtx 20 cla patients 3 groups show differences baseline characteristics also post hoc analysis iptw psadjusted models revealed patients ocr lower risk arr patients cla expbocr 0485 ci 95 02640893 p 0020 result confirmed also 12month mri activity expbocr 0248 ci 95 00650948 p 0042 differences found pairwise comparisons ocr vs rtx rtx vs cla investigated outcomes aes similar among 3 groups anticd20 drugs revealed effective safe options ntz exit strategies investigated dmts showed good safety profilepmid33844155 doi101007 s13311021010372,0.0
targeting adenosine receptors neurological diseases cell reprogram 2021 apr 23 2 5772 doi 101089 cell20200087abstractadenosine plays significant role neurotransmission process controlling blood pressure adenosine triphosphate atp acts neuromodulator neurotransmitter activation p2 receptors regulates contractility heart adenosine signaling essential process regeneration regulating proliferation differentiation apoptosis stem cells review selected neurological disorders alzheimers disease parkinsons disease amyotrophic lateral sclerosis multiple sclerosis epilepsy clinical trials using antagonists epigenetic tools targeting adenosine receptor therapeutic approach treatment disorders promising results reported many clinical trials found higher expression levels a2a p2x7 receptors neurological disorders complicate disease condition therefore modulations receptors using antagonists receptors sam sadenosylmethionine therapy epigenetic tool useful reversing complications disorders finally suggest modulation adenosine receptors neurological disorders can increase regenerative phase increasing rate proliferation differentiation damaged tissuespmid33861641 doi101089 cell20200087,0.0
realworld retrospective study effectiveness safety fingolimod relapsing remitting multiple sclerosis middle east north africa finomena clin neurol neurosurg 2021 feb 25 203106576 doi 101016 jclineuro2021106576 online ahead printabstractobjectives evidence effectiveness safety fingolimod realworld clinical practice middle east north african mena region limited study aimed evaluate effectiveness safety fingolimod patients relapsingremitting multiple sclerosis rrms realworld setting mena regionpatients methods rrms patients treated fingolimod least 12 months retrospectively identified databases 34 centers across mena region study outcomes included annualized relapse rate arr relapsefree rate rfr time first second relapses mean change expanded disability status scale edss proportion patients magnetic resonance imaging mri activity evidence disease activity neda 3 retention patients treatment well safety measuresresults total 806 patients included 6634 female mean age 3297 962 years mean disease duration 492 466 years mean fingolimod use 372 167 months patients received previous diseasemodifying therapy 7965 compared year preceding fingolimod initiation rfr improved 33008635 p 0001 arr decreased 084 073 016 045 p 0005 edss decreased 269 174201 166 p 0001 proportion patients gadoliniumenhancing t1 lesions decreased 5784 1293 p 0001 12 months fingolimod treatment neda3 achieved 413 patients median time first second relapses reached since 8635 9839 patients experienced relapses first time second time respectively eighthundred one 9938 patients continued fingolimod treatment beyond 12 months onehundred thirty patients 1613 experienced adverse events mainly lymphopenia 546 leukopenia 211 13 patients 161 experienced serious adverse eventsconclusion study confirms effectiveness safety profile fingolimod realworld setting middle east north african mena regionpmid33714799 doi101016 jclineuro2021106576,0.0
disability measurement multiple sclerosis patients 55 years older expanded disability status scale really telling clinicians mult scler relat disord 2020 dec 28 49102724 doi 101016 jmsard2020102724 online ahead printabstractbackground expanded disability status scale edss measures disease progression multiple sclerosis ms edss changes assumed due worsening msrelated disability strict interpretation premise may include normal findings abnormal inflating disability score determining cause neurologic symptoms can difficult older population comorbid illness polypharmacyobjective examine association edss age comorbidities polypharmacymethods 106 people 55 years older without ms administered edss validated comorbidity questionnaire polypharmacy also assessedresults median edss scores 60 people ms 30 people without ms participant cohort edss 0 higher edss scores associated older age polypharmacy pyramidal cerebellar functional systems accounted largest percentage unique variance groupsconclusion older individuals without ms demonstrated significant disability edss findings indicate edss scores may partially due factors ms understanding disease course disability may benefit development normative edss scores correct factorspmid33609959 doi101016 jmsard2020102724,0.0
mitochondrial associated er membrane mam compartment dysregulation amyotrophic lateral sclerosis als semin cell dev biol 2021 mar 8s10849521 21 000264 doi 101016 jsemcdb202102002 online ahead printabstractthe endoplasmic reticulum er mitochondria connect multiple contact sites form unique cellular compartment termed mitochondriaassociated er membranes mams mams hubs signalling pathways regulate cellular homeostasis survival metabolism sensitivity apoptosis mams therefore involved vital cellular functions dysregulated several human diseases whilst mam dysfunction increasingly implicated pathogenesis neurodegenerative diseases role amyotrophic lateral sclerosis als poorly understood however als er mitochondrial dysfunction well documented pathophysiological events moreover alterations lipid metabolism neurons regulate processes linked neurodegenerative diseases link lipid metabolism dysfunction als also proposed review discuss structural functional relevance mams als targeting mam therapeutically beneficial disorder disoefdisorderpmid33707063 doi101016 jsemcdb202102002,0.0
pilot study oxidative pathways ms fatigue randomized trial nacetyl cysteine ann clin transl neurol 2021 mar 6 doi 101002 acn351325 online ahead printabstractobjective assess feasibility tolerability safety nacetyl cysteine nac fatigue progressive ms secondary objectives evaluated changes fatigue oxidative pathway biomarkers nac versus placebomethods individuals progressive ms modified fatigue impact scale mfis t38 randomized 21 nac 1250mg tid placebo 4 weeks primary outcome tolerability safety secondary outcome evaluate efficacy mfis change baseline week 4 groups exploratory biomarker outcomes included change blood gsh gssg ratio reducedtooxidized glutathione gsh vivo relative gsh using 7t mr spectroscopy mrs groups fisher exact test used categorical rank sum continuous outcomesresults fifiteen randomized 10 nac 5 placebo mean age 561 years 80 female median edss 60 least one adverse event ae occurred 60 nac versus 80 placebo p 075 two aes attributed nac one patient abdominal pain constipation 94 adherence nac mfis decreased groups week 4 mean improvement 11points nac versus 18points placebo p 033 gsh gssg ratio decreased placebo 06 nac 01 p 018 change gsh levels total creatine anterior posterior cingulate cortex insula caudate putamen thalamus differ groupsinterpretation nac welltolerated progressive ms although reduction fatigue nac similar placebo antioxidant blood mrs biomarkers significantly altered nac due dose route administration time sample collection short halflife lack effect registered clinicaltrialsgov nct02804594pmid33675156 doi101002 acn351325,0.0
sphingosine 1phosphate receptor modulators multiple sclerosis cns drugs 2021 apr 2 doi 101007 s4026302100798w online ahead printabstractfingolimod gilenya received regulatory approval us fda 2010 firstinclass sphingosine 1phosphate s1p receptor s1pr modulator first oral diseasemodifying therapy dmt used treatment relapsing forms multiple sclerosis ms development new class therapeutic compounds continued pharmacological goal high interest clinical trials treatment various autoimmune disorders including ms s1p physiologic signaling molecule acts ligand group cell surface receptors s1prs expressed various body tissues regulate diverse physiological pathological cellular responses involved innate adaptive immune cardiovascular neurological functions subtype 1 s1pr s1pr1 expressed cell surface lymphocytes well known major role ms pathogenesis play important regulatory role egress lymphocytes lymphoid organs lymphatic circulation thus s1pr1directed pharmacological interventions aim modulate role immune cell trafficking sequestration autoreactive lymphocytes lymphoid organs reduce recirculation subsequent infiltration central nervous system indeed receptor subtype selectivity s1pr1 theoretically favored minimize safety concerns related interaction s1pr subtypes improved understanding fingolimods mechanism action provided strategies development selective secondgeneration s1pr modulators selectivity serves reduce important safety concern regarding cardiacrelated side effects bradycardia requires prolonged firstdose monitoring led generation smaller molecules shorter halflives improved onset action requirement phosphorylation activation preserved efficacy shorter halflives secondgeneration agents allow rapid reversal pharmacological effects following treatment discontinuation may beneficial addressing treatmentrelated complications case adverse events managing serious opportunistic infections progressive multifocal leukoencephalopathy eliminating drug pregnancies march 2019 breakthrough ms treatment achieved fda approval second s1pr modulator siponimod mayzent active secondary progressive ms relapsingremitting ms first oral dmt specifically approved active forms secondary progressive ms furthermore ozanimod received fda approval march 2020 treatment relapsing forms ms followed subsequent approvals health canada european commission secondgeneration selective s1pr modulators tested ms statistically significant data phase ii phase iii clinical studies include ponesimod act128800 ceralifimod ono4641 amiselimod mt1303 review covers available data mechanisms action pharmacodynamics kinetics efficacy safety tolerability various s1pr modulators patients relapsingremitting secondary progressive fingolimod primary progressive mspmid33797705 doi101007 s4026302100798w,0.0
treatment antibodymediated encephalomyelitis strategies treatment neuromyelitis optica spectrum disorder myelin oligodendrocyte glycoprotein antibodyassociated disease nervenarzt 2021 mar 30 doi 101007 s00115021010904 online ahead printabstractbackground antibodymediated encephalomyelitis neuromyelitis optica spectrum disorder nmosd myelin oligodendrocyte glycoprotein antibodyassociated disease mogad glial fibrillary acidic protein gfap antibodyassociated astrocytopathy belong group newly described autoimmune diseasesaim presentation treatment antibodymediated encephalomyelitis focus nmosd mogadmethods selective literature search pubmed taking consultation version s2k guidelines german society neurology dgn diagnosis treatment multiple sclerosis ms nmosd mog iggassociated diseases accountresults acute relapses treated highdose steroid pulse therapy apheresis therapy plasma exchange immunoadsorption crucial start treatment quickly possible apheresis therapy can also used firstline treatment certain conditions prophylactic immunotherapy steroids classical immunosuppressants monoclonal antibodies specific mechanisms action used eculizumab inebilizumab satralizumab first drugs approved nmosd symptomatic treatment neurorehabilitation important complementary measuresconclusion treatment antibodymediated encephalomyelitis differs treatment multiple sclerosis requires specific measurespmid33783551 doi101007 s00115021010904,1.0
improving quality affordability equity multiple sclerosis care ann clin transl neurol 2021 mar 10 doi 101002 acn351326 online ahead printabstractobjective prevailing approaches selecting multiple sclerosis ms disease modifying therapies dmts contributed exponential increases societal expenditures outofpocket expenses without compelling evidence improved outcomes guidance lacking regarding benefits preventing msrelated disability likely outweighs risks highly effective dmts het appropriate consider dmt costs objective develop standardized approach improve quality affordability equity ms caremethods ms experts partnered health plan pharmacists develop ethical riskstratified costsensitive treatment algorithm developed riskstratification schema classify patients relapsing forms ms high intermediate low risk disability based best available evidence evidence poor lacking consensus dmts grouped highly modestly low uncertain effectiveness preferentially ranked within groups safety based prespecified criteria reviewed fda documents published literature efficacy safety equivalent lower cost dmt preferredresults assignment highrisk group prompts treatment preferred hets early disease course persons intermediate lowrisk groups cost health care access barriers incorporated induction therapy affordable bcell depleting agent based favorable safety profiles preferred approach prioritizes use rituximab natalizumab among hets interferonbetas glatiramer acetate among modestly effective agentsinterpretation riskstratified treatment approach recommend provides clear measurable guidance prescribe hets prioritize lower cost dmts accommodate persons ms cost barriers dmt use can adapted cost structures updated quickly new information emerges recommend physician groups partner health insurance plans adapt approach settings particularly united states future studies needed resolve considerable uncertainty much variability prognosis specific risk factors explainpmid33751857 doi101002 acn351326,0.0
aquaporin 4 antibodypositive neuromyelitis optica spectrum disorders myelin oligodendrocyte glycoprotein antibodyassociated encephalomyelitis abrief review nervenarzt 2021 mar 31 doi 101007 s0011502101106z online ahead printabstractaquaporin 4 aqp4 immunoglobulin ig gassociated neuromyelitis optica spectrum disorders nmosd myelin oligodendrocyte glycoprotein immunoglobulin ig gassociated encephalomyelitis mogem also termed mog antibodyassociated disease mogad important autoimmune differential diagnoses multiple sclerosis ms differ ms respect optimum treatment prognosis aqp4 iggpositive nmosd take relapsing course virtually cases mogem least 80 adult cases diseases can quickly lead permanent disability left untreated although mogem associated better overall longterm prognosis antibody testing must carried means socalled cellbased assays number red flags defined must checked prior making diagnosis nmosd mogem acute attacks treated using highdose glucocorticoids plasma exchange immunoadsorption rituximab immunosuppressants used offlabel attack prevention recently eculizumab c5 complement inhibitor approved european union eu treatment patients aqp4 iggpositive nmosd article gives brief overview clinical paraclinical features pathology treatment prognosis rare disorderspmid33787942 doi101007 s0011502101106z,1.0
differential diagnostics autoimmune inflammatory spinal cord diseases nervenarzt 2021 mar 25 doi 101007 s00115021010922 online ahead printabstractmyelitis acute subacute inflammatory syndrome spinal cord myelopathy often used synonym presenting similar symptoms clinical practice can caused numerous primarily inflammatory etiologies might also show progressive disease course within last decade spectrum autoimmune myelitis significantly broadened spectrum diagnostic methods apart characteristic example multiple sclerosis shortlength myelitis neuromyelitis optica spectrum disorders longitudinally extensive transverse myelitis multiple rare important differential diagnoses also considered magnetic resonance imaging laboratory analyses serum antibodies cerebrospinal fluid important diagnostic methods fundamental rapid treatment decisions subsequently better prognosis article reviews representative diseases within spectrum autoimmune spinal cord diseases differential diagnosespmid33765163 doi101007 s00115021010922,0.0
susceptibilityweighted imaging technical essentials clinical neurologic applications radiology 2021 feb 23203071 doi 101148 radiol2021203071 online ahead printabstractsusceptibilityweighted imaging swi evolved simple twodimensional t2weighted sequences threedimensional sequences improved spatial resolution enhanced susceptibility contrast swi mri sequence sensitive compounds distort local magnetic field eg calcium iron phase information can differentiate term swi colloquially used denote highspatialresolution susceptibilityenhanced sequences across different mri vendors sequences even phase information used imaging appearance swi related sequences strongly depends acquisition technique initially swi related sequences mostly used improve depiction findings already known standard twodimensional t2weighted neuroimaging microbleeds patients aging dementia mild brain trauma increased conspicuity superficial siderosis alzheimer disease amyloid angiopathy iron deposition neurodegenerative diseases abnormal vascular structures capillary telangiectasia swi also helps identify findings visible standard t2weighted images nigrosome 1 parkinson disease dementia lewy bodies central vein peripheral rim signs multiple sclerosis peripheral rim sign abscesses arterial signal loss related thrombus asymmetrically prominent cortical veins stroke intratumoral susceptibility signals brain neoplasmspmid33620291 doi101148 radiol2021203071,0.0
machine deep learning multiple sclerosis research just powerful statistics commentary mult scler 2021 feb 241352458521996699 doi 101177 1352458521996699 online ahead printno abstractpmid33625275 doi101177 1352458521996699,0.0
othello syndrome delusional disorder jealous type violence cns spectr 2021 apr 26 2 160161 doi 101017 s1092852920002588abstractbackground othello syndrome also known morbid jealousy pathological jealousy conjugal paranoia rare delusional disorder related partners infidelity large scale comprehensive studies delusional jealousy case reports cases series leave delusional disorder jealous type ddjt largely unknown herein report case ddjt possible etiology describe characteristics comorbidities interventionscase description 65yearold married retired disabled caucasian male history closed traumatic brain injury chronic pain presented outpatient care accompanied wife chief complaint paranoid delusions patient car racer sustained 25 total body surface area burns motor vehicle crashed speed almost 160 mph patient coma nine weeks coded three times resuscitated time per imaging patient suffered subarachnoid hemorrhage right outer parietal left front parietal lobes patient developed chronic pain extensive burns opioids many years gradually tapered six years ago last couple years patient experienced cognitive decline associated disorientation memory deficit patient perseverative wifes trip two years ago patient believed affair one mutual acquaintances patient denied visual auditory hallucinations continued express love affection toward wife although wife continually provided reassurance multiple family members confirmed faithfulness patient minimal insight delusion expressed disappointment loss sexual intimacy wife patient prescribed duloxetine 60mg trazodone 150mg mood anxiety sleep stable patient also started taking pimozide 1mg nightly since beginning year good responsediscussion dsm estimates prevalence ddjt less 1 least third cases show neurological basis involving frontal lobe dysfunction associated strokes parkinsons disease brain trauma tumors neurodegenerative disorder encephalitis multiple sclerosis even normal pressure hydrocephalus association alcohol amphetamine cocaine dopamine therapy pergolide ropinirole levodopa amantadine pramipexole reported finally ddjt known risk factor violent crimes including homicide treatment pimozide shows strongest evidence patients show improvement antipsychotic medication along cbt continued research clinical trials warranted ddjt considering patients positive response interventions ddjt can become dangerous condition forensic situationspmid34127129 doi101017 s1092852920002588,0.0
safety diseasemodifying treatments sarscov2 antibodypositive multiple sclerosis patients mult scler relat disord 2021 jan 13 49102754 doi 101016 jmsard2021102754 online ahead printabstractbackground coronavirus disease 2019 covid19 raises particular concerns people multiple sclerosis pwms diseasemodifying treatments dmts physicians caring impact severe acute respiratory syndrome coronavirus 2 sarscov2 infection pwms receiving dmts inhibit immune cell trafficking natalizumab ntz fingolimod fty remains determined possible effects drugs infection related diseaseaims describe selfreported covid19 symptoms disease severity pwms ntz fty received serology confirmation sarscov2 infectionmethods 27th april 3rd may 2020 telephone interviews conducted 140 pwms treatment ntz fty order collect structured data multiple sclerosis ms covid19 patients followed center classified symptomatic paucisymptomatic asymptomatic basis selfreported clinical characteristics covid19 severity rated 7point ordinal scale addition period 4th may 3rd june 2020 sarscov2 serology testing using roche sarscov2 igg assay elecsys performed 104 140 742 interviewed pwms 50 treated ntz 54 fty results 14 104 134 pwms ntz fty antisarscov2 antibodies 8 met criteria asymptomatic 3 paucisymptomatic 3 symptomatic covid19 covid19 severity score lower 3 none required hospitalization showed severe covid19 complicationsconclusions despite relatively high sars cov2 seroprevalence found sample pwms positive cases showed either mild covid19 symptoms reassuring findings indicate lack covid19 complications pwms dmts support hypothesis safe maintain ongoing treatment drugs current settingpmid33609958 doi101016 jmsard2021102754,0.0
oxidized phosphatidylcholines found multiple sclerosis lesions mediate neurodegeneration neutralized microglia nat neurosci 2021 feb 18 doi 101038 s4159302100801z online ahead printabstractneurodegeneration occurring multiple sclerosis ms contributes progression disability therefore important identify neutralize mechanisms promote neurodegeneration ms report oxidized phosphatidylcholines oxpcs found ms lesions previously identified endproduct markers oxidative stress potent drivers neurodegeneration cultured neurons oligodendrocytes killed oxpcs ameliorated microglia oxpc injection mouse spinal cords developed focal demyelinating lesions prominent axonal loss depletion microglia accumulated oxpc lesions exacerbated neurodegeneration singlecell rna sequencing lesioned spinal cords identified unique subsets trem2high mouse microglia responding oxpc deposition trem2 detected human ms lesions trem2 mice exhibited worsened oxpc lesions results identify oxpcs potent neurotoxins suggest enhancing microgliamediated oxpc clearance via trem2 help prevent neurodegeneration mspmid33603230 doi101038 s4159302100801z,1.0
videogamebased approach measuring information processing speed multiple sclerosis patients games health j 2021 apr 10 2 115120 doi 101089 g4h20200069abstractobjective slowing information processing speed ips biomarker neuronal damage patients multiple sclerosis pwms focus ips might ideal solution perspective promptly detecting cognitive changes time developed tabletbased homemade videogame test sensitivity device measuring subclinical ips pwms materials methods fortythree pwms without cognitive impairment 20 healthy controls hcs administered videogame task tablet response times rts accuracy recorded results pwms mean rts 5055 739 ms significantly slower hcs mean rts 4623 403 ms p 0014 videogame task moderate significant correlation r 035 p 003 mean rts symbol digit modalities test observed conclusion videogame showed good sensitivity measuring ips apparently cognitive normal pwms computerized testing might useful screening initial cognitive dysfunction monitored marker underlying disease progression irb approval number 2332cescpmid33818136 doi101089 g4h20200069,0.0
blue rubber bleb nevus syndrome associated tuberous sclerosis complex cns involvement neurosciences riyadh 2021 apr 26 2 207211 doi 1017712 nsj2021220200111abstractblue rubber bleb nevus syndrome brbns rare disorder characterized multiple domeshaped cutaneous venous malformations skin visceral organs typical extracutaneous lesions appearance blueish nippleshaped nodules can easily compress refill described rare case 23yearold female brbns tuberous sclerosis complex tsc presented central nervous system cns involvement including unprovoked focal impaired awareness seizure brbns presents hemangiomas involving multiple organs body including brain gastrointestinal gi system skin case highlights importance studying understanding association brbns tsc may lead improved understandingpmid33814375 doi1017712 nsj2021220200111,0.0
effects covid19 quot sheltering placequot activity people multiple sclerosis neurol clin pract 2021 apr 11 2 e216e218 doi 101212 cpj0000000000000982no abstractpmid33842099 pmcpmc8032435 doi101212 cpj0000000000000982,0.0
safety efficacy fingolimod iranian patients relapsingremitting multiple sclerosis openlabel study caspian j intern med 2021 apr 12 3 263274 doi 1022088 cjim123263abstractbackground fingolimod first oral therapy approved treating relapsingremitting multiple sclerosis rrms 2010 openlabel study evaluated safety efficacy fingolider 05 mg iranian ms patients oneyear followupmethods multicenter openlabel longitudinal designed evaluate safety efficacy fingolider 05 mg oneyear followup period across 11 centers patients visited neurologists every two months evaluate possible adverse events clinical disease activity considered recording kurtzkes expanded disability status scale edss results total 252 patients mean treatment duration 3434570 days 20 patients experienced adverse events aes serious adverse events saes resistant urinary tract infection uti premature atrial contraction pac skin allergic reaction macular edema chicken pox zona panic attacks exacerbations associated steroids treatment led fingolider discontinuation mean edss decreased 215129 95ci 199to232 baseline 185122 95ci 168to202 12th month final visit pvalue revealed significant differences comparing baseline final edss p0001 mean annualized relapse rate arr patients one year prior study 00060016 95ci 0004to0008 changed 00050016 95ci 0003to0007 end study period patients 12month period fingolider treatment experienced sustained arr disease progression p0001 conclusion obtained findings suggest administration fingolider 05 mg fingolimod osvahpharma tehran iran safe efficient iranian ms patientspmid34221275 pmcpmc8223042 doi1022088 cjim123263,0.0
perilesional neurodegenerative injury multiple sclerosis relation focal lesions impact disability mult scler relat disord 2021 jan 5 49102738 doi 101016 jmsard2021102738 online ahead printabstractbackground axonal injury primary source irreversible neurological decline persons multiple sclerosis pwms identifying quantifying myelin axonal loss lesional perilesional tissue vivo fundamental better understanding multiple sclerosis ms outcomes patient impairment using advanced magnetic resonance imaging mri methods consisting selective inversion recovery quantitative magnetization transfer imaging sirqmt multicompartment diffusion mri spherical mean technique smt conducted crosssectional pilot study assess myelin axonal damage normal appearing white matter nawm surrounding chronic black holes cbhs pathology correlates disability vivo hypothesized lesional axonal transection propagates tissue injury surrounding nawm degree injury related patient disabilitymethods eighteen pwms underwent 30 tesla conventional clinical mri inclusive t1 t2 weighted protocols well sirqmt smt regions interests rois manually delineated cbhs nawm neighboring cbhs perilesional nawm distant ipsilateral nawm contralateral distant nawm sirqmtderived macromoleculartofree pool size ratio psr smtderived apparent axonal volume fraction vax extracted infer myelin axonal content respectively group differences assessed using mixedeffects regression models correlation analyses obtained bootstrapping 95 confidence intervalresults comparison perilesional nawm psr vax values reduced cbhs p 00001 increased distant contralateral nawm rois p 0001 psr p 00001 vax ipsilateral nawm p 0176 psr p 0549 vax vax values measured cbhs correlated perilesional nawm pearson rho 063 p 0001 statistically relevant associations seen psr vax values clinical mri metrics disease exception cbh psr values correlated expanded disability status scale pearson rho 063 p 003 conclusions results show myelin axonal content detected psr vax reduced perilesional nawm function degree focal cbh axonal injury finding indicative ongoing anterograde retrograde degeneration suggests treatment prevention cbh development key factor preserving nawm integrity surrounding tissue also suggests measuring changes perilesional areas time may useful measure outcome proofofconcept clinical trials neuroprotection repair psr vax largely failed capture associations clinical mri characteristics likely result small sample size crosssectional design however longitudinal assessment larger cohort may unravel impact pathology disease progressionpmid33609957 doi101016 jmsard2021102738,1.0
altered communication dynamics reflect cognitive deficits temporal lobe epilepsy epilepsia 2021 mar 11 doi 101111 epi16864 online ahead printabstractobjective although temporal lobe epilepsy tle recognized systemlevel disorder little work investigated pathoconnectomics dynamic perspective leveraging computational simulations quantify patterns information flow across connectome tested hypothesis network communication abnormal condition studied interplay hippocampal networklevel disease effects assessed associations cognitionmethods simulated signal spreading via linear threshold model temporally evolves structural graph derived diffusionweighted magnetic resonance imaging mri comparing homogeneous group 31 patients histologically proven hippocampal sclerosis 31 age sexmatched healthy controls evaluated modulatory effects structural alterations neocortex hippocampus network dynamics furthermore multivariate statistics addressed relationship cognitive parametersresults observed slowing outspreading times across multiple areas bilaterally indexing delayed information flow strongest effects ipsilateral frontotemporal regions thalamus hippocampus effects markedly reduced controlling hippocampal volume cortical thickness underscoring central role hippocampus wholebrain disease expression multivariate analysis associated slower spreading time frontoparietal limbic default mode subcortical networks impairment across tasks tapping sensorimotor executive memory verbal abilitiessignificance moving beyond descriptions static topology toward formulation brain dynamics work provides novel insight structurally mediated network dysfunction demonstrates altered wholebrain communication dynamics contribute common cognitive difficulties tlepmid33705572 doi101111 epi16864,0.0
machine deep learning ms research just powerful statistics yes mult scler 2021 feb 241352458520981309 doi 101177 1352458520981309 online ahead printno abstractpmid33625280 doi101177 1352458520981309,0.0
psoriasis decision tree j clin aesthet dermatol 2021 apr 14 4 1422 epub 2021 apr 1abstractpsoriasis inflammatory disorder skin associated increased risk systemic diseases psoriatic arthritis psychiatric disorders malignancy cardiometabolic inflammatory bowel diseases careful consideration presence comorbidities guide selection appropriate therapy evolution therapeutic targets treatment psoriasis significantly advanced available treatment options potentially leading uncertainty selecting optimal treatment patient article review evidencebased guidelines use psoriasis treatments patients distinct comorbidities group appropriate therapeutic options visual aid easytouse visual tool incorporating treatment options best suited specific comorbidities can increase physicians confidence selecting appropriate treatment individualized basispmid34055182 pmcpmc8142826,0.0
ozanimod multiple sclerosis aust prescr 2021 apr 44 2 6566 doi 1018773 austprescr2021013 epub 2021 mar 10no abstractpmid33911338 pmcpmc8075748 doi1018773 austprescr2021013,0.0
tscinsensitive rheb mutations induce oncogenic transformation combination constitutively active mtorc1 signalling proteome remodelling cell mol life sci 2021 apr 8 doi 101007 s00018021038257 online ahead printabstractthe mechanistic target rapamycin complex 1 mtorc1 important regulator cellular metabolism commonly hyperactivated cancer recent cancer genome screens identified multiple mutations rashomolog enriched brain rheb primary activator mtorc1 might act driver oncogenes causing hyperactivation mtorc1 show number recurrently occurring rheb mutants drive hyperactive mtorc1 signalling differing levels insensitivity primary inactivator rheb tuberous sclerosis complex show two activated mutants rhebt23m e40k strongly drive increased cell growth proliferation anchorageindependent growth resulting enhanced tumour growth vivo proteomic analysis cells expressing mutations revealed surprisingly two mutants promote distinct oncogenic pathways rhebt23m driving increased rate anaerobic glycolysis rhebe40k regulates translation factor eef2 autophagy likely differential interactions 5 ampactivated protein kinase ampk modulate activity findings suggest unique personalized combination therapies may utilised treat cancers according rheb mutant harbourpmid33834258 doi101007 s00018021038257,0.0
abnormalcortical thickness relapsingremitting multiple sclerosis correlations cognition impairment effect modified bushenyisui decoction cognitive function multiple sclerosis j tradit chin med 2021 apr 41 2 316325abstractobjective investigate changes subcortical gray matter volume cortical thickness andexplorethe correlations regional abnormalities cortical thickness cognitive impairment effect modified bushenyisui decoction bsysd cognitive function multiple sclerosis ms methods prospective study approved institutional review board 92 subjects recruited including 46 relapsingremitting multiple sclerosis rrms patients 46 healthy controls hc 46 patients 22 patients experienced treatment bsysd half year conventional threedimensional t1weighted sequence acquired participants 30 tesla magnetic resonance system basic information detailed cognitive scales montreal cognitive assessment moca symbol digit modalities test sdmt immediate memory delayed recall longterm recognition evaluated subcortical gray matter volume cortical thickness weremeasured freesurfer correlations cortical thickness ms patients showed reduced respect hc cognitive scales wereanalyzed pearson correlation rrms patients influence modified bsysd ms patients cognition analyzed paired t testresults moca immediate memory delayed recall longterm delayed recognition rrms significantly decreased hc gray matter atrophy measured freesurfer showed mainly thalamus hippocampus rrms patients compared hc cortical thickness several regions frontal lobe parietal lobe temporal lobe hippocampal cingulate gyrus fusiform gyrus rrms patients decreased significant difference regions cortical thickness thinning related moca immediate memory delayed recall longterm delayed recognition temporal lobe fusiform gyrus modified bsysd improve moca sdmt immediate memory delayed recall longterm delayed recognition ms patients promote recovery cognitive function ms patientsconclusions gray matter atrophy cortical thickness thinning validated rrms cortical thickness thinning temporal lobe fusiform gyrus strongly related cognitive deficits rrms modified bsysd promote recovery cognitive function mspmid33825413,0.0
implementation reflex locomotion program according vojta produces shortterm automatic postural control changes patients multiple sclerosis j bodyw mov ther 2021 apr 26401405 doi 101016 jjbmt202101001 epub 2021 jan 9abstractbackground imbalance common people multiple sclerosisobjective examine effectiveness vojta locomotion reflex program shortterm automatic postural control patients multiple sclerosismethods quasiexperimental controlled trial pretestposttest designparticipants people multiple sclerosis n 21 able walk 100 m unable maintain 30s tandem stance arms alongside bodyintervention two consecutive weeks two interventions conducted vojta group standard therapy group b primary outcome berg balance scale bbs tandem test 10 m walk 1st session pre post end study 2 weeks laterresults intervention significant results contrast intervention b bbs referred equilibrium variables p 0026 tandem test p 001 10 m walk test significant improvement seen interventions p 000 group p 0038 group b addition association found variable core activation main equilibrium variable bbs intervention aconclusions results suggest vojta therapy shortterm effect improved balance everyday skills according bbs tests walking people ms compared standard therapeutic procedure wwwclinicaltrialgovregistration number nct03887507pmid33992274 doi101016 jjbmt202101001,0.0
microglia clean toxic lipids multiple sclerosis nat neurosci 2021 mar 23 doi 101038 s41593021008291 online ahead printno abstractpmid33758401 doi101038 s41593021008291,0.0
ambient air pollution multiple sclerosis systematic review rev environ health 2021 jan 4 36 4 535544 doi 101515 reveh20200079 print 2021 dec 20abstractobjectives studies shown environmental risk factors including air pollution might related incidence recurrence multiple sclerosis ms systematic review conducted investigate relation air pollution msmethods systematic search conducted pubmed scopus science direct embase web science january 2020 restrictions search strategy conducted air pollution key words co pm25 pm10 so2 no2 exposure key word multiple sclerosis outcomeresults eventually applying inclusion exclusion criteria 17 articles included methodologies outcomes reported heterogeneous different metrics used results therefore conducting metaanalysis possible eight studies analyzed relation particulate matter pm prevalence relapse ms observed significant relation no2 nox associated recurrence prevalence ms three studies three cohort studies association observed air pollution recurrence occurrence msconclusions results systematic review show outdoor air pollution especially pm nitrogen oxides might related prevalence relapse mspmid34821118 doi101515 reveh20200079,0.0
emerging therapeutic applications fumarates trends pharmacol sci 2021 feb 19s01656147 21 000079 doi 101016 jtips202101004 online ahead printabstractfumarates successfully used treatment psoriasis multiple sclerosis antioxidative immunomodulatory neuroprotective properties make fumarates attractive therapeutic candidates pathologies exact working mechanisms fumarates however fully understood elucidation mechanisms required drugs successfully repurposed diseases towards administration route dosage treatment timing frequency duration important parameters consider optimize clinical paradigms mind summarize rapidly expanding literature pharmacokinetics pharmacodynamics fumarates including discussion two recently fdaapproved fumarates vumeritytm bafiertamtm review emerging applications fumarates focusing neurological cardiovascular diseasespmid33618840 doi101016 jtips202101004,1.0
development psychometric properties multiple sclerosis knowledge assessment scale rasch analysis novel tool evaluating ms knowledge mult scler 2021 apr 27 5 767777 doi 101177 1352458520929626 epub 2020 jun 17abstractbackground multiple sclerosis ms related knowledge important evaluation metric health education interventions however ms knowledge assessment tools currently available useobjectives study aims develop reliable valid multiple sclerosis knowledge assessment scale mskas use ms community general publicmethods mskas developed using delphi study methodology administered participants first open enrolment understanding multiple sclerosis ums online course rasch analysis used examine psychometric properties develop final scaleresults experts across ms community participated development mskas resulting initial scale 42 items five hundred fortythree ums participants completed mskas 89 female 30 people ms final unidimensional 22item scale person separation index 216 person reliability index 082 item separation index 1119 cronbachs alpha kr20 test reliability 087conclusion mskas unidimensional scale good construct validity internal consistency mskas potential useful assessment ms knowledge research clinical practicepmid33739199 doi101177 1352458520929626,0.0
ultrasonographic imaging systemic sclerosis digital ulcers systematic literature review validation steps semin arthritis rheum 2021 feb 19 51 2 425429 doi 101016 jsemarthrit202102008 online ahead printabstractintroduction background skin ulcers complex array clinical manifestations systemic sclerosis ssc often difficult treat however definition sscskin ulcers date promising demonstrating poor reliability accuracy emerging data ultrasound significant potential evaluate sscskin ulcersobjective perform systematic literature review slr understand degree ultrasound ssc skin ulcers validated according omeract criteriamethods slr investigated cochrane library web science pubmed databases manuscripts inception 1st april 2020 inclusion exclusion criteria included manuscripts ssc patients aged 16 years performing sscrelated skin ulcer evaluation ultrasound machines papers animal model diseases ssc venous ulcers excluded data extraction used uniform case report form collected data patient demographics disease activity description ultrasound machine procedures degree domains validity fulfilled manuscript evaluation extraction performed two independent assessors third author consulted case disagreementresults amongst 308 manuscripts identified 6 published manuscripts posters fulfilled inclusion exclusion criteria extracted face validity found three studies developed us definition ssculcers across patients content validity one study evaluated concordance us image clinical assessment criterion validity shown one study ultrasound detected improvement sensitivity change sscskin ulcer response therapy feasibility demonstrated us use skin ulcers multiple settings 6 manuuscripts posters conclusion systematic literature review shows ultrasound skin ulcers ssc partially validated face content criterion validity responsiveness reasonable feasibility validation construct validity reliability discrimination requiredpmid33677309 doi101016 jsemarthrit202102008,0.0
hidradenitis suppurativa role interleukin17 aryl hydrocarbon receptor link possible fungal aetiology med hypotheses 2021 feb 10 149110530 doi 101016 jmehy2021110530 online ahead printabstracthidradenitis suppurativa hs chronic recurrent debilitating skin disease hair follicle usually presents puberty painful deepseated inflamed lesions apocrine gland bearing areas body commonly axillae inguinal anogenital regions pathophysiology disease remains elusive newer therapies targeting various aspects dysregulated immune system presents useful opportunity look cytokine profile hs inflammatory conditions share similar patterns aim teasing less considered explanations hs pathogenesis observed il17 appears common denominator linking hs immune mediated diseases like crohn ulcerative colitis multiple sclerosis psoriasis given il17 plays important role antifungal immunity evidenced cytokine pattern fungal disease bulk data citing potential involvement crohn ulcerative colitis multiple sclerosis psoriasis fair suggest need explore role fungi play setting hs going forward aryl hydrocarbon receptor ahr ubiquitous largely conserved entity gaining interest inflammatory conditions psoriasis atopic dermatitis well known modulate autoimmune states activation exogenous endogenous agents result secretion il17 th17 cells one agents tryptophan metabolite 6formylindolo 3 2b carbazole ficz can produced microorganisms fungi will interesting explore usefulness hs pathogenesispmid33607406 doi101016 jmehy2021110530,0.0
machine deep learning ms research just powerful statistics mult scler 2021 feb 241352458520978648 doi 101177 1352458520978648 online ahead printno abstractpmid33625302 doi101177 1352458520978648,0.0
leveraging electronic health records data predict multiple sclerosis disease activity ann clin transl neurol 2021 feb 24 doi 101002 acn351324 online ahead printabstractobjective relapse risk prediction tool currently available guide treatment selection multiple sclerosis ms leveraging electronic health record ehr data readily available point care developed clinical tool predicting ms relapse riskmethods using data clinicbased research registry linked ehr system 2006 2016 developed models predicting relapse events registry training set n 1435 tested model performance independent validation set ms patients n 186 iterative process identified prior 1year relapse history key predictor future relapse ascertaining relapse history laborintensive chart review impractical pursued twostage algorithm development 1 l1 regularized logistic regression lasso phenotype past 1year relapse status contemporaneous ehr data 2 lasso predict future 1year relapse risk using imputed prior 1year relapse status algorithmselected featuresresults final model comprising age disease duration imputed prior 1year relapse history achieved predictive auc f score 0707 0307 respectively performance significantly better baseline model age sex race ethnicity disease duration noninferior model containing actual prior 1year relapse history predicted risk probability declined disease duration ageconclusion novel machinelearning algorithm predicts 1year ms relapse accuracy comparable clinical prediction tools applicability point care ehrbased twostage approach outcome prediction may application neurological disease beyond mspmid33626237 doi101002 acn351324,1.0
impact complement activation clinical outcomes multiple sclerosis ann clin transl neurol 2021 mar 1 doi 101002 acn351334 online ahead printabstractwe determined activation profiles classical alternative complement pathway 39 treatmentnave patients early relapseonset ms plasma concentrations complement fragments unchanged ms compared 32 patients noninflammatory neurological diseases profiles patients experiencing clinical exacerbations differ patients stable disease correlate baseline edss numbers t2 lesions time second relapse longterm edss outcomes 4 years diagnosis significantly correlate baseline complement levels data support use complement activation products biomarkers disease activity early mspmid33646629 doi101002 acn351334,0.0
functional genomic analyses highlight shift gpr17regulated cellular processes oligodendrocyte progenitor cells underlying myelin dysregulation aged mouse cerebrum aging cell 2021 mar 5e13335 doi 101111 acel13335 online ahead printabstractbrain ageing characterised decline neuronal function associated cognitive deficits increasing evidence myelin disruption important factor contributes agerelated loss brain plasticity repair responses brain myelin produced oligodendrocytes generated throughout life oligodendrocyte progenitor cells opcs currently leading hypothesis points ageing major reason ultimate breakdown remyelination multiple sclerosis ms however incomplete understanding cellular molecular processes underlying brain ageing hinders development regenerative strategies combined systems biology neurobiological approach demonstrate oligodendroglial myelin genes amongst altered ageing mouse cerebrum underscored identification causal links signalling pathways downstream transcriptional networks define oligodendroglial disruption ageing results highlighted gprotein coupled receptor gpr17 central disruption opcs ageing confirmed genetic fatemapping cellular analyses finally used systems biology strategies identify therapeutic agents rejuvenate opcs restore myelination agerelated neuropathological contextspmid33675110 doi101111 acel13335,1.0
developing clinical pathway identify manage cognitive problems multiple sclerosis qualitative findings patients family members charity volunteers clinicians healthcare commissioners mult scler relat disord 2020 oct 4 49102563 doi 101016 jmsard2020102563 online ahead printabstractbackground cognitive problems common debilitating symptom multiple sclerosis ms screening treatment cognitive problems recommended however routinely delivered uk clinics collected synthesised stakeholder perspectives develop care pathway cognitive problems ms produce logic model illustrating pathway might operatemethods fortynine stakeholders including people ms care providers participated semistructured interviews focus groups participants viewed information illustrated pathway might work provided feedback data transcribed verbatim analysed using framework analysis mapped onto preliminary logic model accompanying thematic frameworkresults proposed pathway perceived helpful providing standardised support neglected ms symptom training packages online cognitive screening triaging decisions viewed crucial activities shared responsibility personcentred approach addressing complexity cognitive problems important engagement mechanisms allocating time clinic appointments within staff workloads essential resources implementationconclusion coconstructed ms cognitive screening management pathway will evaluated clinical costeffectiveness trial however interim clinicians can adapt implement pathway services evaluate locallypmid33677366 doi101016 jmsard2020102563,0.0
retention physical gains community following physical training multiple sclerosis systematic review implications semin neurol 2021 mar 9 doi 101055 s00411725139 online ahead printabstractmultiple sclerosis ms progressive neurological illness whose typically young adult onset results nearly entire lifetime worsening disability despite unrelenting neurodegenerative disease numerous clinical trials past 40 years ms vigorously attempted improve least stabilize declining physical function although vast majority studies assessed training effects within controlled laboratory clinic settings recent years growing interest emerged test whether newer therapies can instead benefit reallife activities community nonetheless comparatively little attention paid whether training gains can retained meaningful periods review discusses comparative success various physical training methods benefit withincommunity activities ms whether gains can retained long afterward review will suggest future research directions toward establishing efficacious treatments can allow persons ms reclaim physical abilities maximize functionality meaningful periodspmid33690875 doi101055 s00411725139,0.0
inter intrarater reliability modified tardieu scale assessing spasticity knee extensors patients multiple sclerosis j bodyw mov ther 2021 apr 26515518 doi 101016 jjbmt202009004 epub 2020 sep 17abstractintroduction spasticity one common disabling symptoms multiple sclerosis ms clinical tool assessing spasticity study aimed investigate inter intrarater reliability modified tardieu scale assessing knee extensors spasticity ms patientsmethods twentysix patients ms 12 females 14 males mean age 40 1139 years participated study extensor muscles knees evaluated using mts two sessions first session two examiners randomly assessed knee extensor spasticity study interrater reliability 34 days later first examiner assessed patients determine intrarater reliability intraclass correlation coefficient icc analysis twoway random effect model used determine reliability various components modified tardieu scaleresults interrater reliability quality muscle reaction knee extensor muscles good icc 089 difference angle muscle response r1 full range r2 movement r2 r1 spasticity intensity criterion good icc 073 icc values r2r1 muscle response quality assessments one rater 073 082 respectivelyconclusion findings current study showed mts good good inter intrarater reliability assessing knee extensors spasticity ms patientspmid33992290 doi101016 jjbmt202009004,1.0
siponimod multiple sclerosis aust prescr 2021 apr 44 2 6970 doi 1018773 austprescr2021014 epub 2021 apr 1no abstractpmid33911340 pmcpmc8075740 doi1018773 austprescr2021014,0.0
sexuality multiple sclerosis patient doctor perspectives j sex med 2021 mar 17s17436095 21 002241 doi 101016 jjsxm202101178 online ahead printabstractbackground little known address sexuality clinical care patients multiple sclerosis pwms aim describe contrast perception sexuality associated aspects communication pwms treating neurologists msologists provide standard caremethods patients surveyed using 13item questionnaire investigating perception sexuality opinions communication sexuality context ms certified msologists austria received 18item survey regarding approach taking sexual history patientsoutcomes report frequency answers given survey propose possible standard care sexuality addressed clinical routineresults ninetythree pwms mean age 39 11 years 57 female 75 msologists mean age 43 9 years 63 male completed survey seventysix percent patients report sexuality important 95 think sexual dysfunction influence quality life 84 like asked sexuality msologist contrast 15 msologists reported discussing sexuality every patient common reason fear crossing personal borders 34 strong desire medical education subject 76 clinical implications discussing sexuality important pwms msologists consider patients wishes needs talk itstrengths limitations largest survey contrasting views patients treating physicians topic communication sexuality use empirical unvalidated questionnaire may introduced bias moreover patients open talk sexuality may potentially overrepresented studyconclusion msologists offer patients open opportunity appropriate framework discuss sexuality consultation altmann p leithner k leutmezer f et al sexuality multiple sclerosis patient doctor perspectives j sex med 2021 xxxxxxxxpmid33744180 doi101016 jjsxm202101178,0.0
qsm imaging biomarker chronic glial activation multiple sclerosis lesions ann clin transl neurol 2021 mar 11 doi 101002 acn351338 online ahead printabstractbackground inflammation chronic active lesions occurs behind closed bloodbrain barrier detected mri activated microglia highly enriched iron can visualized quantitative susceptibility mapping qsm mri technique used delineate ironobjective characterize histopathological correlates different qsm hyperintensity patterns ms lesionsmethods ms brain slabs imaged mri qsm processed histology immunolabeled cells quantified lesion rim center adjacent normalappearing white matter nawm iron+ myeloid cell densities rims correlated susceptibilities humaninduced pluripotent stem cell ipsc derived microglia used determine effect iron production reactive oxygen species ros proinflammatory cytokinesresults qsm hyperintensity lesion perimeter correlated activated iron+ myeloid cells rim nawm lesions high punctate homogenous qsm signal contained minimally activated iron myeloid cells vitro iron accumulation highest m1polarized human ipscderived microglia enhance ros cytokine productionconclusion high qsm signal outlining lesion rim punctate signal center biomarker chronic inflammation white matter lesionspmid33704933 doi101002 acn351338,0.0
therapeutic effects peptidylprolyl cis trans isomerase pin1 inhibitor juglone animalmodel experimental autoimmune encephalomyelitis j physiol pharmacol 2021 apr 72 2 doi 1026402 jpp2021205 epub 2021 aug 6abstractmultiple sclerosis ms chronic inflammatory demyelinating disease central nervous system cns currently satisfactory treatment disease pin1 known peptidylprolyl cis trans isomerase ppiase involved many cellular processes including immune responses numerous studies shown juglone effectively inhibits pin1 activity however effect pin1 inhibitor juglone autoimmune diseases multiple sclerosis ms animal model experimental autoimmune encephalomyelitis eae remain incomplete present study aimed explore therapeutic effects pin1 inhibitor juglone eae eae induced c57bl 6 mice myelin oligodendrocyte glycoprotein mog 3555 treatment juglone health status eae observed inflammation explored using pathological analysis impact juglone immune cells examined using intracellular staining flow cytometry results demonstrated juglone ameliorates eae reduces inflammation demyelination cns study also found juglone suppresses pathogenic th1 th17 cells expression cd83 mhcii dendritic cells eae addition juglone ameliorates eae pin1 inhibitors therefore hold great promise autoimmune disease ms therapypmid34374656 doi1026402 jpp2021205,1.0
targeting citrullination autoimmunity insights learned preclinical mouse models expert opin ther targets 2021 apr 26 doi 101080 1472822220211918104 online ahead printabstractintroduction aberrant citrullination excessive peptidylarginine deiminase pad activity detected numerous challenging autoimmune diseases rheumatoid arthritis inflammatory bowel diseases systemic lupus erythematosus multiple sclerosis type 1 diabetes excessive pad activity common denominator diseases pads interesting potential therapeutic targets future therapiesareas covered review summarizes advances made design pad inhibitors utilization therapeutic potential preclinical mouse models autoimmunityrelevant literature encompasses studies 1994 2021 available pubmedgovexpert opinion panpad inhibition promising therapeutic strategy autoimmune diseases drugs achieving panpad inhibition capable ameliorating reversing preventing clinical symptoms preclinical mouse models however implications pads key biological processes potentially presents high risk clinical complications hamper translation pad inhibitors clinic envisage pad isozymespecific inhibitors will improve understanding role pad isozymes disease pathology reduce risk sideeffects enhance prospects future clinical translationpmid33896351 doi101080 1472822220211918104,0.0
current concepts communication central nervous system peripheral immunity via lymphatics roles lymphatics play brain spinal cord disease pathogenesis biol futur 2021 mar 72 1 4560 doi 101007 s42977021000664 epub 2021 feb 1abstractthe central nervous system cns lacks conventional lymphatics within cns parenchyma yet still maintains fluid homeostasis immunosurveillance cns communicates systemic immunity thus topic interest scientists past century led several theories cns drainage routes addition perineural routes rediscoveries lymphatics surrounding cns meninges revealed extensive network lymphatics now know play significant role fluid homeostasis immunosurveillance meningeal lymphatic networks exist along superior sagittal sinus transverse sinus dorsal brain near cribriform plate olfactory bulbs base brain surrounding spinal cord inhibition one lymphatic networks can reduce cns autoimmunity mouse model multiple sclerosis ms augmenting lymphatic networks can improve immunosurveillance immunotherapy clearance glioblastoma alzheimers disease traumatic brain injury cerebrovascular injury review will provide historical context cns drainage contributes immune surveillance recently published studies fit meningeal lymphatics context cns homeostasis neuroinflammation identify complex dualities lymphatic function neuroinflammation therapeutics targeting lymphatic function may complicated currently appreciated conclude identifying unresolved questions controversies may guide future researchpmid34554497 doi101007 s42977021000664,0.0
disease progression obstetric outcomes women multiple sclerosis reference center northeastern brazil rev bras ginecol obstet 2021 mar 43 3 165171 doi 101055 s00401722157 epub 2021 apr 15abstractobjective describe obstetric outcomes patients multiple sclerosis ms impact pregnancy postpartum period progression diseasemethods case series study performed december 2019 february 2020 reporting pregnancies occurred 1996 2019 subjects included women ms undergoing followup ms referral center northeastern brazil least one pregnancy onset ms symptoms first relapse first year deliveryresults total 26 women 38 pregnancies analyzed 32 resulted delivery remaining 6 miscarriages significant increase prevalence relapse postpartum period compared gestational period 16 421 pregnancies exposure diseasemodifying therapies dmts 14 368 interferon 2 53 fingolimod higher rates abortion prematurity low birth weight reported group exposed dmt compared one notconclusion sample present study significant increase rate ms relapse postpartum period compared gestational period additionally seems exposure dmts pregnancy may affect obstetric outcomes patientspmid33860499 doi101055 s00401722157,0.0
nurses#39 stories beirut 2020 explosive disaster top pandemic economic crises int nurs rev 2021 mar 68 1 18 doi 101111 inr12675abstractthe world health organization designated last year international year nurse midwife know worldwide 2020 became unforgettable year nurses midwives everywhere confronted covid19 pandemic nurse 2020 challenging heroic nurse 2020 beirut lebanon extraordinarily charged adversity country witnessed oneyear series tragedies epic dimensions laying heavy toll frontline nurses present stories eight lebanese nurses giving voice incredible experiences ongoing resilience face adversities served emergency department beirut city hospital catastrophic explosion occurred capital 4th august 2020 reported duty disaster immense magnitude now coping aftermath trauma nurses faced many traumas country experienced war terrorism decades arising disaster challenges pandemic give policy recommendations deserve urgent attention lebanon underscore need disaster preparation funding education importantly mental health care nurses health professionals help support international communitypmid33891770 doi101111 inr12675,0.0
translation crosscultural adaptation reliability validity turkish version sfqualiveen people multiple sclerosis neurourol urodyn 2021 mar 1 doi 101002 nau24645 online ahead printabstractaims short form qualiveen sfqualiveen simple easy understand valid scale used evaluate effect urologic problems quality life neurological patients aim study translate culturally adapt validate turkish version sfqualiveen people multiple sclerosis pwms methods translation cultural adaptation questionnaire carried obtaining necessary permissions decide final turkish version sfqualiveen ten pwms urologic problems pretested patients included study asked complete turkish sfqualiveen urinary distress inventoryshort form udi6 questionnaires validity reliability scale determined retest 2 weeks laterresults sixtythree pwms urologic problems enrolled internal consistency cronbachs 087 reproducibility intraclass correlation coefficient icc 097 good total sfqualiveen cronbachs icc values ranged 043 077 088098 sfqualiveen subscales respectively content validity questionnaire appropriate moderate correlation founded sfqualiveen udi6 r 062 p 0001 floor ceiling effects studyconclusion turkish version sfqualiveen valid reliable questionnaire pwmspmid33645839 doi101002 nau24645,0.0
dermoscopic findings case multiple subungual fibromas acta dermatovenerol alp pannonica adriat 2021 mar 30 1 3537abstractperiungual subungual fibromas also known koenen tumors diagnostic findings tuberous sclerosis clinical appearance histological features characterize ungual fibromas well defined however dermoscopic findings benign tumors reported previously report rare presentation multiple subungual fibromas fingers developmentally delayed patient tuberous sclerosis along dermoscopic features ungual tumorspmid33765756,0.0
value blink reflex early diagnosis multiple sclerosis acta clin croat 2021 mar 60 1 1015 doi 1020471 acc2021600102abstractthe aim determine differences blink reflex clinically definite multiple sclerosis cdms clinically isolated syndrome cis patients presented symptoms signs brainstem impairment study included 20 patients diagnosed cdms 20 cis 20 healthy controls recorded latencies early r1 late component ipsilaterally r2 contralaterally r2 occurrence irritative component r3 analyzed data sex age signs brainstem impairment magnetic resonance imaging mri findings presence brainstem demyelinating lesions statistically significant difference patient groups according sex age symptoms brainstem involvement mri findings statistically significant difference r1 component latencies r2 latencies right side latencies r2 left r2 right statistically longer cdms group difference appearance r3 component conclusion blink reflex found sensitive useful diagnostic tool assessment brainstem structures especially abnormalities seen cdms also cis slowing late component sign dysfunction efferent part reflex arc specific highly sensitive findingpmid34588716 pmcpmc8305361 doi1020471 acc2021600102,0.0
multiple sclerosis b cell therapy covid19 vaccine eneurologicalsci 2021 mar 22100319 doi 101016 jensci2021100319 epub 2021 jan 21no abstractpmid33521339 pmcpmc7826102 doi101016 jensci2021100319,0.0
ginseng polysaccharides potential neuroprotective agent j ginseng res 2021 mar 45 2 211217 doi 101016 jjgr202009002 epub 2020 sep 11abstractthe treatments nervous system diseases nsds long difficult issues researchers complexity pathogenesis advent aging society searching effective treatments nsds become hot topic ginseng polysaccharides gp main biologically active substance ginseng various biological properties immuneregulation antioxidant antiinflammation etc considering association effects gp pathogenesis neurological disorders many related experiments conducted recent years paper reviewed previous studies effects mechanisms gp diseases related nervous system found gp play ameliorative role nsds regulation immune system inflammatory response oxidative damage signaling pathway structureactivity relationship also discussed summarized addition provided new insights gp promising neuroprotective agent development utilizationpmid33841001 pmcpmc8020291 doi101016 jjgr202009002,1.0
safety evaluation shorter infusion ocrelizumab substudy phase iiib chords trial ann clin transl neurol 2021 feb 23 doi 101002 acn351310 online ahead printabstractthe chords trial evaluated ocrelizumab ocr patients relapsingremitting multiple sclerosis suboptimal response previous diseasemodifying treatment objective present study assess safety shorter ocr infusions substudy chords completing four doses ocr per initial us prescribing recommendations main study participants substudy n 129 received fifth dose 2h duration vs 35 h infusionrelated reactions occurred 124 patients none severe lifethreatening led treatment discontinuation shorter infusion time change safety profile ocr clinicaltrialsgov nct0237856 pmid33621404 doi101002 acn351310,0.0
effectiveness group counseling clientcentered approach based gather principles sexual satisfaction women multiple sclerosis randomized clinical trial iran j med sci 2021 mar 46 2 103111 doi 1030476 ijms2020826161074abstractbackground multiple sclerosis ms prevalent progressive sensory neurological disability young adults important psychological consequences present study designed assess effectiveness group counseling clientcentered approach based gather principles sexual satisfaction women msmethods clinical trial conducted january 2018 may 2019 ms referral center tehran iran 72 eligible participants assigned intervention control groups 36 group via simple randomization intervention group received group counseling based clientcentered approach control group received routine counseling data collected using larson sexual satisfaction questionnaire lssq three different time points intervention final session one month intervention collected data analyzed spss software version 19 order analyze obtained data independent t test mannwhitney u test paired t test wilcoxon test chisquare test fisher exact test friedman test usedresults mean score sexual satisfaction intervention showed statistically significant difference two groups based friedman test intervention group trend changes mean score sexual satisfaction significant difference intervention final session one month intervention p0001 however significant difference observed control groupconclusion results showed effectiveness group counseling clientcentered approach based gather principles sexual satisfaction intimacy among women ms trial registration number irct20180110038302n3pmid33753954 pmcpmc7966937 doi1030476 ijms2020826161074,0.0
effects diminished positive mood depressed mood upon verbal learning memory among people multiple sclerosis j clin exp neuropsychol 2021 feb 23112 doi 101080 1380339520201853066 online ahead printabstractobjective cognitive impairment affects many 65 people multiple sclerosis pwms memory impairment confers greater severity disability functional impairment depression also common among pwms lifetime prevalence rates high 50 research yet clearly define relationship memory dysfunction depression among pwms may reflect incomplete assessment depressive symptoms present study examined different aspects depressive symptoms including anhedonia ie diminished positive mood relationships verbal learning memory among pwmsmethod participants 48 healthy individuals 96 pwms primarily caucasian 903 female 750 participants completed california verbal learning test2 cvlt2 assess verbal learning memory chicago multiscale depression inventory assess depressed mood cmdimood diminished positive mood cmdidpm results linear regression revealed main effect cmdidpm interaction cmdidpm cmdimood significantly explained variance across learning recall recognition cvlt2 indices followup analyses indicated cmdidpm significant absence high cmdimood scores cmdimood explained variance cvlt2 trial bconclusions depressed mood little direct effect upon memory performance pwms absence severe depressed mood higher levels positive mood corresponded better memory performance however impact diminished positive mood rendered null among endorsing high levels depressed mood data may imply anhedonia corresponds poorer memory function among pwms suggests investigators clinicians assess multiple mood dimensions among pwmspmid33622171 doi101080 1380339520201853066,0.0
evaluating infectious neoplastic immunological degenerative diseases central nervous system cerebrospinal fluidbased nextgeneration sequencing mol diagn ther 2021 mar 1 doi 101007 s4029102100513x online ahead printabstractcerebrospinal fluid csf clear paucicellular fluid circulates within ventricular system subarachnoid space central nervous system cns diverse cns disorders can impact composition volume flow conventional csf testing suffers suboptimal sensitivity review aimed evaluate role nextgeneration sequencing ngs workup infectious neoplastic neuroimmunological neurodegenerative cns diseases metagenomic ngs showed improved sensitivitycompared traditional methodsto detect bacterial viral parasitic fungal infections overall performance maximized studies diagnostic modalities used patients primary cns cancer ngs findings csf largely concordant molecular signatures derived tissuebased molecular analysis interest additional mutations identified csf glioma studies reflecting intratumoral heterogeneity patients metastasis cns ngs facilitated diagnosis prognosis therapeutic management monitoring exhibiting higher sensitivity neuroimaging cytology plasmabased molecular analysis although evidence still rudimentary ngs enhance diagnosis pathogenetic understanding multiple sclerosis addition alzheimer parkinson disease conclude ngs shown potential aid research facilitate diagnostic approach improve management outcomes aforementioned cns diseases however establish role clinical practice clinical validity utility ngs protocol determined lastly evidence derived small retrospective studies results randomized control trials significant valuepmid33646562 doi101007 s4029102100513x,0.0
kv13 k+ channel immune system quot precision pharmacologyquot using peptide toxins biol futur 2021 mar 72 1 7583 doi 101007 s42977021000717 epub 2021 feb 6abstractsince discovery kv13 voltagegated k+ channel human t cells 1984 ion channels considered crucial elements signal transduction machinery immune system knowledge kv13 inhibitors outstanding motivated potential application autoimmune diseases mediated kv13 overexpressing effector memory t cells eg multiple sclerosis high affinity kv13 inhibitors either small organic molecules eg pap1 peptides isolated venomous animals date highest affinity kv13 inhibitors best kv13 selectivity engineered analogues sea anemone peptide shk eg shk186 engineered scorpion toxin hstx1 r14a natural scorpion toxin vm24 peptides inhibit kv13 picomolar concentrations several thousandfold selective kv13 biologically critical ion channels despite significant progress field kv13 molecular pharmacology several progressive questions remain elucidated discussed include conjugation peptides carriers increase residency time peptides circulation eg pegylation engineering peptides antibodies use rational drug design create novel peptide inhibitors understanding potential offtarget effects kv13 inhibitionpmid34554500 doi101007 s42977021000717,0.0
sporadic multiple renal angiomyolipoma lymph node involvement case report literature review j int med res 2021 mar 49 3 3000605211001710 doi 101177 03000605211001710abstractangiomyolipoma aml benign tumor mainly occurs kidneys simultaneous involvement kidney local regional lymph nodes rare might misdiagnosed metastasizing malignant cancer present study 50yearold woman referred hospital routine health screening ultrasound sporadic multiple renal aml lymph node involvement suspected based clinical manifestations radiologic features partial nephrectomy performed parainferior vena cava lymph node removed pathologic results confirmed multiple aml lymph node invasion also reviewed englishlanguage literature regarding renal aml lymph node involvement found middleaged women likely develop disease loin pain main presenting feature patients history tuberous sclerosis complex radical nephrectomy predominant treatment local recurrence distant metastasis occurred patients radical nephrectomy partial nephrectomy conclusion renal aml lymph node involvement rare can occur patients tuberous sclerosis complex multiple sporadic aml partial nephrectomy firstline treatment treatment necessarypmid33788657 doi101177 03000605211001710,0.0
natalizumab safety risk patients relapsingremitting multiple sclerosis eur j hosp pharm 2021 mar 28 2 112114 doi 101136 ejhpharm2019002048 epub 2019 oct 16abstractobjective estimate risk progressive multifocal leukoencephalopathy pml safety natalizumab administration patients relapsingremitting multiple sclerosis rrms methods descriptive retrospective observational study including patients rrms treated natalizumab followedup 10 yearsthe likelihood developing pml estimated based three risk factors antijohn cunningham virus antibody index previous immunosuppressive therapy duration treatment patients classified five categories minimum probability 01 1000 low 01 1000 mediumlow 0206 1000 mediumhigh 083 1000 high probability 310 1000 results 34 patients included probability pml last cycle 559 minimum 88 low 118 mediumlow 3 mediumhigh 205 high 12 patients continue active treatment natalizumab cases pml confirmed adverse effects detected 50 patientsconclusions quantifying risk factors allows us estimate probability pml appearance thus assessing maintenance suspension natalizumabpmid33608441 doi101136 ejhpharm2019002048,0.0
covid19 patients multiple sclerosis associations diseasemodifying therapies cns drugs 2021 mar 20 doi 101007 s40263021008041 online ahead printabstractbackground diseasemodifying therapies dmts multiple sclerosis ms target immunity potential increase risk severe acute respiratory syndrome coronavirus2 sarscov2 infection alter clinical course assessed risks patients ms pwms objective objective study describe overall risk coronavirus disease 2019 covid19 infection severe disease course potential populationlevel predictors covid19 infection pwms provide context using cohort patients systemic lupus erythematosus sle addition association different ms dmts incidence clinical course covid19 evaluated safety data biogen global safety database also presented reported cases covid19 patients treated biogen ms therapiesmethods ibm explorys electronic health record database 72 000 000 patients us healthcare networks identified patients ms sle without polymerase chain reactionconfirmed covid19 covid19 cumulative incidence hospitalization deaths among dmt classes compared using logistic regression adjusted age sex body mass index comorbidities race ethnicity secondary data source assess safety data covid19 reports biogen ms therapies extracted described biogens global safety databaseresults 30 478 pwms open dmt prescription identified within explorys 344 covid19 positive significant risk factors acquiring covid19 comorbidity score 1 body mass index 30 black african ancestry similar risk factors also identified patients sle patients ms less likely develop covid19 treated interferons 061 glatiramer acetate 051 vs ms dmts p 0001 anticd20 therapy associated highest risk 345 p 00001 biogen global safety database identified 1217 patients covid19 positive treated intramuscular interferon beta1a peginterferon beta1a natalizumab dimethyl fumarate diroximel fumarate fampridineconclusions comorbidities obesity black african ancestry age associated higher risk sarscov2 infection pwms interferons glatiramer acetate associated reduced covid19 risk whereas anticd20 therapies associated increased risk within treated ms cohort covid19 safety reports patients receiving biogen ms therapies consistent explorys database ms literature illustrating replicability power approachpmid33743151 doi101007 s40263021008041,0.0
constructing validating diagnostic nomogram multiple sclerosis via bioinformatic analysis 3 biotech 2021 mar 11 3 127 doi 101007 s13205021026751 epub 2021 feb 16abstractthe purpose study identify biomarkers construct diagnostic prediction model multiple sclerosis ms microarray datasets gene expression omnibus geo downloaded weighted gene coexpression analysis wgcna used search hub modules biomarkers related ms gene ontology go kyoto encyclopedia genes genomes kegg analyses used roughly define biological functions pathways least absolute shrinkage selection operator lasso regression multivariate logistic regression analysis used identify diagnostic biomarkers construct nomogram calibration curve receiver operating characteristic roc curve used judge diagnostic predictive ability addition celltype identification estimating relative subsets rna transcripts cibersort algorithm used calculate proportion 22 kinds immune cells gse41850 used training set gse17048 used test set wgcna revealed one hub module containing 165 hub genes biological functions pathways related cell metabolism immune cell activation diagnostic nomogram contained arpc5 rod1 ubqln2 znf281 abca1 fas roc curve calibration curve training set test set confirmed nomogram great prediction ability addition monocytes m0 macrophages significantly different ms patients healthy people expression arpc5 znf281 abca1 correlated m0 macrophages nomogram provides new insights contributes accurate diagnosis mssupplementary information online version contains supplementary material available 101007 s13205021026751pmid33680693 pmcpmc7886954 doi101007 s13205021026751,0.0
remote regulation type 2 immunity intestinal parasites semin immunol 2021 nov 18101530 doi 101016 jsmim2021101530 online ahead printabstractthe intestinal tract target organ parasitic infections including helminths protozoa parasites elicit prototypical type 2 immune activation hosts immune system striking impact local tissue microenvironment despite local containment parasites within intestinal tract parasitic infections also mediate immune adaptation peripheral organs review summarize current knowledge guttissue axes influence important immunemediated resistance disease tolerance context coinfections elaborate implications parasiteregulated gutlung gutbrain axes development severity airway inflammation central nervous system diseasespmid34802872 doi101016 jsmim2021101530,0.0
hiv infection multiple sclerosis case unexpected quot evidence disease activityquot status j int med res 2021 mar 49 3 300060521999577 doi 101177 0300060521999577abstractmultiple sclerosis ms inflammatory demyelinating disease central nervous system whose etiology remains unclear suggested ms can triggered certain viruses however human immunodeficiency virus hiv infection associated reduced incidence ms present case young patient diagnosed active relapsingremitting ms whose clinical course substantially improved following hiv infection treatment patient achieved evidence disease activity status without diseasemodifying drugs hivinduced immunosuppression antiretroviral therapy may attenuated clinical course patientpmid33765893 doi101177 0300060521999577,1.0
sex therapy reasonable necessary support persons disability j law med 2021 mar 28 2 323335abstracthistorically inadequate recognition need persons disabilities opportunity meaningful sexual expression many impediments lie way recognition disability professional assistance required precedentsetting decision full court federal court australia national disability insurance agency v wrmf 2020 276 fcr 415 2020 fcafc 79 woman multiple sclerosis accepted onto national disability insurance scheme affirmed eligible taxpayerfunded receipt services sex worker spite national disability insurance scheme declined services constituting reasonable necessary support however may decision will overturned controversial legislative amendment section reviews reasoning decision human rights political issues raised decision require consideration engagementpmid33768744,0.0
tumefactive demyelinating lesion tdl shinkei geka 2021 mar 49 2 376382 doi 1011477 mf1436204401abstracttumefactive demyelinating lesion tdl defined large lesion size 2 cm mass effect perilesional edema ring enhancement tdl occur multiple sclerosis ms neuromyelitis optica spectrum disorder nmosd acute disseminated encephalomyelitis adem immunological diseases noninvasive methods including mr imaging assay several autoantibodies eg aquaporin4 autoantibodies recommended tdl identified radiological findings mri characterized size 2 cm mass effect perilesional edema t2 weighted hypointense rim peripheral diffusion restriction open ring enhancement vascular enhancement central vein sign atypical clinical radiological presentations present patients tdl diagnosis may necessitate brain biopsy due exclude alternative pathology eg primary central nervous system lymphoma treatments outcomes patients tdl dependent disease etiology including ms nmosd adem others always clarify entire picture behind diseasepmid33762460 doi1011477 mf1436204401,1.0
possibilities using effects ozone therapy neurology neuro endocrinol lett 2021 mar 2 42 1 1321 online ahead printabstractobjectives beneficial effects ozone therapy consist mainly promotion blood circulation peripheral central ischemia immunomodulatory effect energy boost regenerative reparative properties correction chronic oxidative stress ozone therapy increases interest new neuroprotective strategies may represent therapeutic targets minimizing effects oxidative stressmethods overview examines latest literature neurological pathologies treated ozone therapy well experience ozone therapy effectiveness treatments connected ability ozone therapy reactivate antioxidant system address oxidative stress chronic neurodegenerative diseases strokes pathologies application options include large small autohemotherapy intramuscular application intraarticular intradiscal paravertebral epidural noninvasive rectal transdermal mucosal ozonated oils ointments combination different types ozone therapy stimulates benefits effects ozoneresults clinical studies o2o3 therapy shown efficient treatment neurological degenerative disorders multiple sclerosis cardiovascular peripheral vascular orthopedic gastrointestinal genitourinary pathologies fibromyalgia skin diseases wound healing diabetes ulcers infectious diseases lung diseases including pandemic disease caused covid19 coronavirusconclusion ozone therapy relatively fast administration ozone gas correct dose administered side effects occur clinical experimental studies will needed determine optimal administration schedule evaluate combination ozone therapy therapies increase effectiveness treatmentpmid33932964,1.0
pharmacological economic analysis application magnetic resonance contrast mediums containing gadolinium case multiple sclerosis probl sotsialnoi gig zdravookhranenniiai istor med 2021 mar 29 2 343346 doi 1032687 0869866x2021292343346abstractthe article considers issues pharmacoeconomics applying gadoliniumcontaining contrast medium diagnostic multiple sclerosis patientsmaterials methods ms excel calculator applied estimate costs analyze impact budget treatment multiple sclerosis exacerbations diagnosed using various gadoliniumcontaining contrast mediums direct medical costs diagnostics gadoliniumcontaining contrast medium hospitalization due exacerbation accordance mandatory medical insurance system taken accountthe results expense reducing number multiple sclerosis exacerbations due use singlemolar gadoliniumcontaining contrast medium gadobutrol compared semipolar gadoliniumcontaining contrast medium gadodiamide gadoteric acid gadoteridol 1000 patients possible reduce financial expenses 1 968 642 7 175 520 rubconclusion cost magnetic resonance imaging diagnostics contrast enhancement treatment multiple sclerosis exacerbations increases series gadobutrol gadodiamide jodas expoim gadodiamide ge health care gadoteridol gadoteric acidpmid33901380 doi1032687 0869866x2021292343346,0.0
memory multiple sclerosis reappraisal using item specific deficit approach neuropsychology 2021 feb 35 2 207219 doi 101037 neu0000712abstractobjective many 65 people multiple sclerosis ms clinically significant memory impairment nature deficit controversial investigations suggest inability retrieve newly learned information memory prominent whereas others imply compromised acquisition accounts impairment prior research simultaneously evaluated acquisition retrieval processes ms fewer attempted account initial acquisition studying retrieval item specific deficit approach isda offers method quantifying acquisition retrieval retention processes latter two mechanisms adjusted initial acquisition simultaneously quantify acquisition retrieval abilities isda applied list learning performance two independent samples people ms corresponding healthy comparison groupsparticipants methods study 1 included 85 people ms 47 healthy individuals study 2 involved separate sample 79 people ms 22 healthy people administered neuropsychological batteries participants ms classified globally impaired unimpaired california verbal learning testii administered assess newlearning studies responses scored using isdaresults studies revealed cognitively impaired people ms manifest weaknesses involving acquisition retrieval nearly identical effect sizes emerged across samples cognitive impairment achieving medium effect upon acquisition large effect upon retrievalconclusions findings accord well previous research showing diminished acquisition retrieval among people ms results may also reconcile contradictory findings extant literature showing memory impairment ms exclusively attributable either acquisition retrieval rather processes may manifest across people ms replication across samples nearly identical effect sizes implies effects reliable possess external validity data hold implications memory rehabilitation interventions involving people ms suggest acquisition retrieval processes addressed treatment psycinfo database record c 2021 apa rights reserved pmid33764111 doi101037 neu0000712,0.0
early recurrent symptoms anterior cervical discectomy fusion done myelopathy int j spine surg 2021 feb 14 s4 s1s4 doi 1014444 7171abstractwe present unique case early recurrent myelopathic clinical manifestations following anterior cervical discectomy fusion however eventual diagnosis multiple sclerosis rather residual cord compression repeat imagingpmid33900936 doi1014444 7171,0.0
vitamin b12 estradiol benzoate improve memory retrieval activation hippocampal akt bdnf creb proteins rat model multiple sclerosis iran j basic med sci 2021 feb 24 2 256263 doi 1022038 ijbms20215146911681abstractobjectives multiple sclerosis ms causes extensive damage hippocampus vitamin b12 vit b12 estradiol benzoate eb antiinflammatory remyelination properties make proper improvement cognitive impairment study aimed evaluate effects compounds learning memory disturbancesmaterials methods 77 adult male rats implanted stainless steel guide cannula bilaterally hippocampal area animals received 3 l intrahippocampal etb 001 randomly divided eleven groups 7 rats group groups included control peanut oil sham1 distilled water sham 2 vit b12 025 05 1 mg kg eb 25 50 mg kg vit b12 025 mg kg plus eb 25 mg kg vit b12 05 mg kg plus eb 25 mg kg vit b12 1 mg kg plus eb 50 mg kg control group received intrahippocampal saline solvent locomotor activity learning memory functions evaluated openfield shuttlebox tests respectively akt creb bdnf levels analyzed western blottingresults study found significant deficit passive avoidance learning locomotor activity well decrease levels phosphorylated akt bdnf creb groups received etb vit b12 1 mg kg eb 50 mg kg combination markedly improved side effectsconclusion study demonstrated vit b12 estradiol benzoate especially combination therapy can helpful treatment memory problems msinduced dysfunction activation hippocampal akt bdnf creb proteinspmid33953866 pmcpmc8061324 doi1022038 ijbms20215146911681,1.0
relationship vitamin d levels cognitive impairment patients multiple sclerosis eur rev med pharmacol sci 2021 feb 25 4 20212030 doi 1026355 eurrev_202102_25105abstractobjective neurocognitive impairment one common manifestations multiple sclerosis ms however pathophysiology issue still poorly understood objective study investigate relationship vitamin d levels cognitive function patients ms assessed cambridge neuropsychological test automated battery cantab patients methods crosssectional casecontrol study subjects 39 saudi patients diagnosed ms participants demographic information including age sex educational level collected participants also evaluated using disease steps scale phq9 scale vitamin d levels assessed participants completed computerized cognitive assessment using cantabresults total sample 39 patients ms 31 795 female physical disability due ms insignificant 25 641 subjects significant 14 359 seventeen 436 participants normal vitamin d levels 22 564 low vitamin d levels ms patients lower mot mean errors control group difference statistically significant t 4313 p 001 moreover scores two groups subcategories memory domain different statistically significant levels furthermore control group higher pal total errors adjusted pal total errors 6 shapes adjusted prm percent correct ms patients p 001 control group also achieved lower scores swm errors swm strategy ms patients p 001 mot mean error found correlate disease steps score r 0394 p 005 significant physical disability r 0457 p 001 memory domain pal total errors adjusted correlated age r 0381 p 005 swm errors correlated age onset disease r 0345 p 005 vitamin d level r 0335 p 005 swm strategy correlated number relapses past 12 months r 0355 p 005 conclusions cognitive performance impaired patients ms vitamin d deficiency potentially modifiable risk factor independently predicted cognitive impairment ms patientspmid33660814 doi1026355 eurrev_202102_25105,0.0
amantadine reappraisal timeless diamondtarget updates novel therapeutic potentials j neural transm vienna 2021 feb 23 doi 101007 s00702021023062 online ahead printabstractthe aim current review provide new indepth insight possible pharmacological targets amantadine pave way extending therapeutic use indications beyond parkinsons disease symptoms viral infections considering amantadines affinities vitro expected concentration targets therapeutic doses humans following primary targets seem plausible aromatic amino acids decarboxylase glialcell derived neurotrophic factor sigma1 receptors phosphodiesterases nicotinic receptors three targets play role lesser extent nmda receptors 5ht3 receptors potassium channels based published clinical studies traumatic brain injury fatigue eg multiple sclerosis ms chorea huntingtons disease regarded potential encouraging indications preclinical investigations suggest amantadines therapeutic potential several indications depression recovery spinal cord injury neuroprotection ms cutaneous pain query database http wwwclinicaltrialsgov reveals research interest several indications cancer autism cocaine abuse ms diabetes attention deficithyperactivity disorder obesity schizophreniapmid33624170 doi101007 s00702021023062,0.0
dietdependent regulation tgf impairs reparative innate immune responses demyelination nat metab 2021 feb 3 2 211227 doi 101038 s42255021003417 epub 2021 feb 18abstractproregenerative responses required restoration nervoussystem functionality demyelinating diseases multiple sclerosis ms yet limiting factors responsible poor cns repair partially understood test impact western diet wd phagocyte function mouse model demyelinating injury requires microglial innate immune function regenerative response occur find wd feeding triggers ageingrelated dysfunctional metabolic response associated impaired myelindebris clearance microglia thereby impairing lesion recovery demyelination mechanistically detect enhanced transforming growth factor beta tgf signalling suppresses activation liver x receptor lxr regulated genes involved cholesterol efflux thereby inhibiting phagocytic clearance myelin cholesterol blocking tgf promoting triggering receptor expressed myeloid cells 2 trem2 activity restores microglia responsiveness myelindebris clearance demyelinating injury thus identified druggable microglial immune checkpoint mechanism regulating microglial response injury promotes remyelinationpmid33619376 doi101038 s42255021003417,1.0
thyroid warthinlike cancer concurrent multiple sclerosis case report j med cases 2021 feb 12 2 7173 doi 1014740 jmc3625 epub 2020 dec 30abstractwarthin likepapillary thyroid cancer wlptc rare malignancy difficult distinguish preoperatively wlptc classic ptc often associated hashimoto thyroiditis ht determines better prognosis low probability recurrence case concerns 43yearold female single thyroid nodule suspected cancer multiple sclerosis ms age 19 thyroid hormone levels normal thyroid antibodies total thyroidectomy lymphadenectomy central compartment performed histological examination revealed warthin likeptc without hashimoto thyroiditis mechanisms involved pathogenesis thyroid cancer patients autoimmune disease completely clear hypothesized local autoimmune response ht contribute determination type cancer also systemic autoimmune disease mspmid34434433 pmcpmc8383610 doi1014740 jmc3625,0.0
lateral suboccipital approach semisitting position resection vagal schwannoma 2dimensional operative video j neurol surg b skull base 2021 feb 82 suppl 1 s51s52 doi 101055 s00401701656 epub 2020 sep 17abstractwe present case sizeable vagal schwannoma resected lateral suboccipital approach semisitting position extraaxial lesion occupying left cerebellomedullary cistern extending pontomedullary junction jugular foramen incidentally discovered 40yearold woman afflicted secondary progressive multiple sclerosis repeated magnetic resonance imaging fig 1 physical examination mild deviation uvula right diminished gag reflex observed patient referred department considerable growth lesion noted broad interdisciplinary consensus reached treat lesion surgically gross total resection achieved histopathology confirmed schwannoma low proliferation index postoperative dysphonia resolved completely within weeks collateral neurological deficit especially functional dysphagia 3year followup indication residual recurrence 2dimensional video demonstrates pre postoperative imaging positioning setup operating room anatomical surgical nuances skull base approach operative technique microdissection schwannoma critical neurovascular structures fig 2 summary lateral suboccipital approach semisitting position powerful tool armamentarium microsurgical management various pathologies residing posterior cranial fossa especially large vascularized schwannomas provided necessary anesthesiological precautions intraoperative procedures semisitting position safe effective link video can found https youtube 9o_qjgkqhg pmid33717819 pmcpmc7936039 doi101055 s00401701656,0.0
ibuprofenbased advanced therapeutics breaking inflammatory link cancer neurodegeneration diseases drug metab rev 2021 apr 5122 doi 101080 0360253220211903488 online ahead printabstractibuprofen classical nonsteroidal antiinflammatory drug nsaid highly prescribed reduce acute pain inflammation array conditions including rheumatoid arthritis osteoarthritis dysmenorrhea gout ibuprofen acts potential inhibitor cyclooxygenase enzymes cox1 cox2 past decades research small molecule led identifying possible therapeutic benefits antitumorigenic neuroprotective functions ibuprofen majorly recognized recent literature need consideration additionally several roles antiinflammatory molecule discovered subjected experimental assessment various diseases however major challenge faced ibuprofen drugs similar classes side effects tendency cause gastrointestinal injury generate cardiovascular risks modulate hepatic acute kidney diseases future research also conducted deduce new methods approaches suppressing unwanted toxic changes mediated drugs develop new therapeutic avenues small molecules continue serve purposes article primarily aims develop comprehensive better understanding ibuprofen pharmacological features therapeutic benefits possible less understood medicinal properties apart major challenges future applicationkey pointsibuprofen nsaid classical antiinflammatory therapeutic agentproapoptotic roles nsaids explored detail past holding key anticancer therapiesexcessive continuous use nsaids may several side effects multiple organ damagehyperactivated inflammation initiates multifold detrimental changes multiple pathological conditionstargeting inflammatory pathways hold key several therapeutic strategies many diseases including cancer microbial infections multiple sclerosis many brain diseasespmid33820460 doi101080 0360253220211903488,1.0
recent developments pet radiotracers tspo applications neuroimaging acta pharm sin b 2021 feb 11 2 373393 doi 101016 japsb202008006 epub 2020 aug 25abstractthe 18 kda translocator protein tspo previously known peripheral benzodiazepine receptor predominately localized outer mitochondrial membrane steroidogenic cells brain tspo expression relatively low physiological conditions upregulated response glial cell activation primary index neuroinflammation tspo implicated pathogenesis progression numerous neuropsychiatric disorders neurodegenerative diseases including alzheimers disease ad amyotrophic lateral sclerosis als parkinsons disease pd multiple sclerosis ms major depressive disorder mdd obsessive compulsive disorder ocd context numerous tspotargeted positron emission tomography pet tracers developed among several radioligands advanced clinical research studies review will overview recent development tspo pet tracers focusing radioligand design radioisotope labeling pharmacokinetics pet imaging evaluation additionally will consider current limitations well translational potential future application tspo radiopharmaceuticals review aims present challenges current tspo pet imaging also provide new perspective tspo targeted pet tracer discovery efforts addressing challenges will facilitate translation tspo clinical studies neuroinflammation associated central nervous system diseasespmid33643818 pmcpmc7893127 doi101016 japsb202008006,0.0
clinical characteristics inflammation coagulation status patients immunological diseaserelated chronic cerebrospinal venous insufficiency ann transl med 2021 feb 9 3 236 doi 1021037 atm204201abstractbackground immunological diseaserelated chronic cerebrospinal venous insufficiency ccsvi rarely reported study aimed analyze clinical characteristics inflammation coagulation status patients immunological diseaserelated ccsvimethods patients ccsvi enrolled 2017 2019 divided three cohorts based immunological disease backgrounds including groups confirmed autoimmune disease suspected subclinical autoimmune disease nonimmunological etiology immunological inflammatory thrombophilia biomarker assay blood samples obtained mannwhitney u test fishers exact test used compare continuous variables categorical variables ccsvi patients without immunological etiology spearmans correlation analysis conducted among age baseline neutrophiltolymphocyte ratio nlr platelettolymphocyte ratio plr interleukin6 il6 creactive protein crp neuronspecific enolase nse three groupsresults total 255 consecutive patients ccsvi enrolled including three subgroups ccsvi confirmed autoimmune disease n41 ccsvi suspected subclinical autoimmune disease n116 ccsvi nonimmunological etiology n98 first subgroup series 41 cases confirmed eight different autoimmune diseases including antiphospholipid syndrome n18 sjgrens syndrome n8 immunoglobulin g4related disease n7 behets disease n2 autoimmune hepatitis n2 wegeners granulomatosis n2 systemic sclerosis n1 aqp4 antibodypositive neuromyelitis optica spectrum disorder n1 groups immunological etiology show higher incidence thrombophilia increased proinflammatory biomarkers eg neutrophil il6 however patients nonimmunological etiology higher baseline level crp additionally baseline plr moderately correlated nlr crp ccsvi patients nonimmunological etiology suspected subclinical autoimmune diseaseconclusions formation ccsvi may based inflammatory process facilitated multiple risk factors among medical history immunological diseases may play significant role due intricate relationship inflammation coagulation moreover ccsvi may also cause independent inflammatory injury venous walls leading focal stenosis thrombus without attacks autoimmune antibodiespmid33708863 pmcpmc7940939 doi1021037 atm204201,0.0
thyroid status possible restore myelin georgian med news 2021 feb 311 143146abstractthe number demyelinating diseases central nervous system prone grow nowadays socially significant well studied one multiple sclerosis search susbstances stop demyelinisation reinforce process remyelination great request thyreoid gland hormones play sufficient role nervous system functioning developing studies show triiodothyronine regulates myelin synthesis thyroidsensitive nuclear receptors study process demyelination modelled via uprizone model appears optimal method since allows witness process demyelination without autoimmune component results study show effectiveness thyroid hormones myelin axon protection rats influence cuprizone behavioral reactions inhibited changes structures neurons cerebral cortex lumbar spinal cord noted severity disorders also depends thyroid status rat organism normal hormonal balance less significant changes noted state hypofunction disorders pronounced cuprizone model demyelination adequate experimental model neurodegeneration behavior disorders thyroid hormones can considered one components new drugs aimed treating multiple sclerosispmid33814408,1.0
gelsolin level patients primary sjogren#39 s syndrome eur rev med pharmacol sci 2021 feb 25 4 20722078 doi 1026355 eurrev_202102_25112abstractobjective gelsolin gsn multifunctional protein can regulate cell proliferation apoptosis inflammation infection gsn reported involved rheumatoid arthritis ra systemic lupus erythematosus sle multiple sclerosis ms many diseases role gsn primary sjogrens syndrome pss remains still unclear aim study investigate changes gsn level serum whole blood cells pss patients evaluate relationship gsn fatigue clinical indicatorspatients methods crosssectional study included 47 pss patients 1 male 46 females average age 52831263 years 51 healthy controls females average age 5061986 years patients collected second affiliated hospital harbin medical university china without age sex differences levels gsn serum pss patients healthy controls measured western blotting sequencing gene expression omnibus geo data national center biotechnology information ncbi gsn levels whole blood cells pss patients healthy controls analyzed r languageresults compared healthy controls level gsn significantly decreased serum pss patients 9889 2894 vs 1316 371 g ml p0001 expression gsn whole blood cells pss patients significantly lower healthy controls 64 019 vs 66 017 p001 compared nonfatigued pss patients level gsn downregulated serum 8569 2708 vs 11152 2471 g ml p001 whole blood cells 643 018 vs 658 021 p0001 fatigue pss patients however significant correlation level gsn eular sjogrens syndrome disease activity index essdai pss patients p073 conclusions gsn decreased serum whole blood cells pss patients much lower fatigue patients nonfatigue patients correlation level gsn essdai significant pss patientspmid33660820 doi1026355 eurrev_202102_25112,0.0
targeting nuclear factorkappa b signaling pathway curcumin implications treatment multiple sclerosis adv exp med biol 2021 12914153 doi 101007 9783030561536_3abstractmultiple sclerosis ms chronic inflammatory disease central nervous system involves autoimmune mechanism leads perivascular demyelination role nuclear factorkappa b nfb signaling pathway pathogenesis ms suggested genomewide association studies therefore strategies targeting pathway potentially beneficial curcumin active component turmeric phenolic phytochemical phytochemical antiinflammatory properties shown multiple studies downregulate nfb downstream gene targets including cyclooxygenase2 tumor necrosis factor interleukin1 interleukin6 review discusses modulatory effects curcumin nfb signaling pathway downstream effectors therapeutic implications modulation mspmid34331683 doi101007 9783030561536_3,1.0
exacerbation multiple sclerosis braf mek treatment malignant melanoma central vein sign distinguish demyelinating lesions metastases j investig med high impact case rep 2021 jandec 923247096211033047 doi 101177 23247096211033047abstractthe emergence immunomodulators effective cancer treatments important advance cancer therapy combination therapy braf mek inhibition without antictla4 treatment causes immunostimulatory effect greatly reduced death melanoma article present case patient prior multiple sclerosis ms later developed metastatic malignant melanoma marked increase magnetic resonance imaging mri findings treatment combination trametinib mek dabrafenib braf diagnostic question metastatic disease versus new ms lesions without brain biopsy discussed healthy 49yearold man diagnosed ms october 2012 stable oral disease modifying drug march 2016 patient discovered lump right groin biopsy positive s100 braf v600 mutation combination mek braf given immunotherapy mri showed 25 new gadoliniumenhancing lesions thought metastases brain biopsy recommended neurology neuroimaging consultation showed mri consistent demyelination oval ovoid homogeneous openring enhancement predominance central vein sign within lesions rather metastasis treatment ms successful return melanoma 4 years new immunotherapies lifesaving modulation immune system can cause unpredictable events markedly increased ms activity awareness diagnostic value central vein sign provided better outcome patient model future otherspmid34308699 doi101177 23247096211033047,1.0
hydrogen sulfide novel immunoinflammatory regulator rheumatoid arthritis adv exp med biol 2021 1315161179 doi 101007 9789811609916_7abstracthydrogen sulfide h2s endogenous gaseous signaling transmitter shown vasodilative antioxidative antiinflammatory cytoprotective activities increasing evidence also indicates h2s can suppress production inflammatory mediators immune cells example t cells macrophages inflammation closely related immune response several diseases rheumatoid arthritis ra multiple sclerosis ms systemic lupus erythematosus sle cancer considering biological effects h2s potential role treatment immunerelated ra exploited present review will provide overview therapeutic potential h2s ra treatmentpmid34302692 doi101007 9789811609916_7,0.0
sarscov2 covid19 patients degree immunosuppression reumatol clin engl ed 2021 augsep 17 7 408419 doi 101016 jreumae202008001 epub 2020 oct 16abstractbackground clear whether patients degree immunosuppression worse outcomes sarscov2 infection compared healthy peopleobjective carry narrative review information available infection sarscov2 immunosuppressed patients especially patients cancer transplanted neurological diseases primary secondary immunodeficienciesresults patients cancer recent cancer treatment chemotherapy surgery sarscov2 infection higher risk worse outcomes transplant patients renal cardiac hepatic neurological pathologies multiple sclerosis ms neuromyelitis optica nmods myasthenia gravis mg primary immunodeficiencies infection human immunodeficiency virus hiv association immunosuppressants studies shown tendency worse outcomesconclusion given little evidence far behaviour sarscov2 infection immunosuppressed patients unclear current studies shown worse outcomes except patients cancerpmid34301385 doi101016 jreumae202008001,0.0
difficulties cerebral toxoplasmosis diagnosis patient multiple sclerosis hiv zh nevrol psikhiatr im s s korsakova 2021 121 6 7680 doi 1017116 jnevro202112106176abstracttoxoplasmosis widespread parasitic disease caused intracellular parasite toxoplasma gondii can affect various tissues organs forming cysts continuing replicate within people intact immune system tissue cysts remain latent state throughout whole life however cases cellular immunodeficiency infection can reactivated leads secondary generalization process people hiv commonly present cerebral toxoplasmosis nonspecific neuroimaging signs well absence pathognomonic symptoms specific laboratory data lead difficulties cerebral toxoplasmosis diagnosis particularly cases history multiple sclerosis similar clinical symptoms brain mri data suggesting tumefactive multiple sclerosis image clinical case cerebral toxoplasmosis female patient multiple sclerosis hiv infection describedpmid34283534 doi1017116 jnevro202112106176,0.0
directions enhancement therapeutic efficacy mesenchymal stem cells different neurodegenerative cardiovascular diseases current status future perspectives curr stem cell res ther 2021 mar 3 doi 102174 1574888x16666210303151237 online ahead printabstractmesenchymal stem cells mscs shown promising therapeutic effects wide variety medical conditions including neurodegenerative disorders cardiovascular diseases although preliminary research emphasized ability mscs engraft sites injury several studies revealed mscs mediate effects release various paracrine factors antioxidant antiinflammatory immunomodulatory antiapoptotic effects however clinical implications mscs application limited due low survival rate conditions inflammation oxidative stress nutrient restriction damaged areas furthermore function isolated mscs usually affected patients health therefore necessary develop new methods enhance therapeutic efficacy mscs pathophysiological conditions review provides overview general properties mscs therapeutic potential neurodegenerative disorders alzheimer disease parkinson disease multiple sclerosis amyotrophic lateral sclerosis huntington disease well cardiovascular diseases myocardial infarction diabetic cardiomyopathy dilated cardiomyopathy related mechanisms addition review also discusses potential problems side effects well current future directions improvement mscs therapy implications applicationspmid33655876 doi102174 1574888x16666210303151237,0.0
case marburg#39 s variant multiple sclerosis successfully treated ivig mitoxantrone ann indian acad neurol 2021 janfeb 24 1 9294 doi 104103 aianaian_117_20 epub 2021 feb 16no abstractpmid33911391 pmcpmc8061517 doi104103 aianaian_117_20,0.0
trigeminal neuralgia patient multiple sclerosis coincidental attack teriflunomideinduced agri 2021 jan 33 1 4245 doi 105505 agri201830316abstracttrigeminal neuralgia attributed multiple sclerosis tnms occurs 2 5 patients multiple sclerosis ms although treatment strategies similar classic trigeminal neuralgia tnms tends become medically resistant require polytherapy demyelinating lesions critical regions common etiology however therapies used treat ms may trigger trigeminal neuralgia well pain disorders like migraines daily headaches presently reported case patient ms suffered severe trigeminal neuralgia 5 months switching teriflunomide oral immunomodulator drug approved relapsingremitting ms discussion possible etiological factors development trigeminal neuralgiapmid34254652 doi105505 agri201830316,1.0
ca2+ homeostasis brain microvascular endothelial cells int rev cell mol biol 2021 36255110 doi 101016 bsircmb202101001 epub 2021 feb 27abstractblood brain barrier bbb formed brain microvascular endothelial cells bmvecs lining wall brain capillaries integrity regulated multiple mechanisms including downregulation tight junction proteins adhesion molecules altered ca2+ homeostasis remodeling cytoskeleton confined level bmvecs beside contribution bmvecs bbb permeability changes cells pericytes astrocytes microglia leukocytes neurons etc also exerting direct indirect modulatory effects bbb alterations bbb integrity play key role multiple brain pathologies including neurological eg epilepsy neurodegenerative disorders eg alzheimers disease parkinsons disease amyotrophic lateral sclerosis etc review principal ca2+ signaling pathways brain microvascular endothelial cells discussed contribution bbb integrity emphasized improving knowledge ca2+ homeostasis alterations bmveca fundamental identify new possible drug targets diminish prevent bbb permeabilization neurological neurodegenerative disorderspmid34253298 doi101016 bsircmb202101001,0.0
retrogasserian radiofrequency thermocoagulation repeatable treatment trigeminal neuralgia unresponsive drug therapy saudi j anaesth 2021 aprjun 15 2 109115 doi 104103 sjasja_972_20 epub 2021 apr 1abstractbackground trigeminal neuralgia present incidence rates ranging 59 126 per 100000 persons although frequent pathology often characterized intense pain extremely significant reduction quality life medical therapy always effective tolerated cases patient can undergo interventional treatments including radiofrequency thermocoagulation still doubts regarding effectiveness time injury parameters repeatability procedurematerials methods analyze patients trigeminal pain undergo retrogasserian radiofrequency single center period 8 years procedure performed following parameters lesion time 60 sec lesion temperature 70c first thermolesion 72c subsequent thermolesions duration benefit number repetitions maneuver incidence adverse events assessedresults totally 122 patients essential trigeminal neuralgia 20 patients trigeminal neuralgia secondary multiple sclerosis analyzed almost patients 965 showed significant reduction pain one procedures time 965 patients showed excellent pain relief 1 40 procedures 60 average time one procedure next 26 monthsconclusion use time temperature parameters chosen shows excellent efficacy line literature low incidence adverse events painfree time one procedure next seem significant prognostic criterion may may indicate repetition procedurepmid34188626 pmcpmc8191261 doi104103 sjasja_972_20,0.0
stressaxis multiple sclerosis clinical cellular molecular aspects handb clin neurol 2021 181119126 doi 101016 b9780128206836000087abstractaltered activity hypothalamuspituitaryadrenal hpa stressaxis implicated pathogenesis progression multiple sclerosis ms linked development specific symptoms comorbidities mood disorders fatigue cognitive dysfunction overall hpaaxis activated hyperresponsive ms though hyporesponsive hpaaxis observed subgroup ms patients severe course disease provide overview possible causes hpaaxis activation sex subtype dependent differences pathological cellular molecular effects clinical correlates hpaaxis activity mspmid34238451 doi101016 b9780128206836000087,0.0
alcohol friend foe autoimmune diseases role gut microbiome gut microbes 2021 jandec 13 1 1916278 doi 101080 1949097620211916278abstractalcohol well known promoting systemic inflammation aggravating multiple chronic health conditions thus alcohol may also expected serve risk factor autoimmune diseases however emerging data human animal studies suggest alcohol may fact protective autoimmune diseases studies point toward alcohols complex dosedependent relationship autoimmune diseases well potential modulation duration type alcohol consumption cultural background sex review will explore alcohols pro antiinflammatory properties human animal autoimmune diseases including autoimmune diabetes thyroid disease systemic lupus erythematosus rheumatoid arthritis experimental autoimmune encephalomyelitis multiple sclerosis will also discuss potential mechanisms alcohols antiinflammatory effects mediated gut microbiomepmid34224314 doi101080 1949097620211916278,0.0
surveillance study acute neurological manifestations among 439 egyptian patients covid19 assiut aswan university hospitals neuroepidemiology 2021 feb 25110 doi 101159 000513647 online ahead printabstractbackground covid19 can accompanied acute neurological complications central peripheral nervous systems cns pns study estimate frequency complications among hospital inpatients covid19 assiut aswan university hospitalsmaterials methods screened patients suspected covid19 admitted 1 june 10 august 2020 university hospitals assiut aswan upper egypt clinical laboratory tests ct mri chest brain neurophysiology study performed patient indicatedresults 439 patients confirmed probable covid19 neurological manifestations occurred 222 117 acute neurological disease remainder nonspecific neuropsychiatric symptoms headache vertigo depression cns affected 75 patients 55 stroke others convulsions 5 encephalitis 6 hypoxic encephalopathy 4 cord myelopathy 2 relapse multiple sclerosis 2 meningoencephalitis 1 pns affected 42 patients majority anosmia ageusia 31 others guillainbarr syndrome 4 peripheral neuropathy 3 myasthenia gravis mg 2 myositis 2 fever respiratory symptoms headache common general symptoms hypertension diabetes mellitus ischemic heart disease common comorbidities patients cns affectionconclusion covid19 cns pns affected stroke common complication cns anosmia ageusia common pns diseases however 6 cases encephalitis 2 cases spinal cord myelopathy 2 cases mg 2 cases myositispmid33631765 doi101159 000513647,0.0
effect ifnbeta treatment plasma levels bdnf il6 relapsingremitting multiple sclerosis patients neuroimmunomodulation 2021 jun 2818 doi 101159 000515595 online ahead printabstractbackground recent investigations addressing neurodegenerative diseases especially multiple sclerosis ms roles brainderived neurotrophic factor bdnf interleukin6 il6 examinedmethods fortyfive relapsingremitting ms rrms patients including 32 ifntreated 13 newly identified untreated cases well 45 sex agematched healthy controls recruited study plasma levels bdnf il6 assessed using elisa method data analyzed spss ver21 results significant differences case healthy control groups terms plasma levels bdnf p value 0044 il6 p value 0001 besides treatment ifn significant impact level bdnf il6 rrms patients compared healthy controls p value 0716 0623 bdnf il6 respectively furthermore increase plasma levels bdnf il6 indicated direct correlation case group r 0508 p value 0008 detail following classification case group 2 subgroups ifntreated untreated patients direct positive correlation observed plasma levels bdnf il6 ifntreated patients r 0495 p value 0026 conclusion ifn treatment seems effective upregulating bdnf il6 rrms patientspmid34182566 doi101159 000515595,0.0
polypharmacy multiple sclerosis current knowledge future directions mo med 2021 mayjun 118 3 239245abstractpolypharmacy daily use five medications well documented older adults linked negative outcomes medication errors adverse drug reactions increased healthcare utilization like older adults people multiple sclerosis pwms susceptible polypharmacy owing variety treatments used address individual multiple sclerosis ms symptoms comorbidities 1565 pwms meet criteria polypharmacy population polypharmacy associated increased reports fatigue subjective cognitive impairment reduced quality life despite evidence adverse outcomes polypharmacy among pwms remains neglected area research article examines current literature regarding polypharmacy ms well implications clinical practice directions future researchpmid34149084 pmcpmc8210980,0.0
effects pde inhibitors multiple sclerosis review vitro vivo models curr pharm des 2021 mar 3 doi 102174 1381612827666210303142356 online ahead printabstractbackground multiple sclerosis ms chronic inflammatory immunemediated disease whose current therapeutic means mostly effective relapsingremitting form ms inflammation still prominent fall short preventing long term impairment however apart inflammationmediated demyelination autoimmune mechanisms play major role ms pathophysiology constituting promising pharmacological target phosphodiesterase pde inhibitors approved clinical use psoriasis undergone trials suggesting neuroprotective effects rendering eligible option accessory ms therapyobjective review discuss potential role pde inhibitors complementary ms therapymethods conducted literature search screened comparatively assessed papers effects pde inhibitor use vitro animal models ms taking account number inclusion exclusion criteriaresults vitro studies indicated pde inhibitors promote remyelination axonal sustenance curbing inflammatory cell infiltration hindering oligodendrocyte neuronal loss suppressing cytokine production vivo studies underlined agents alleviate symptoms reduce disease scores ms animal modelsconclusion pde inhibitors proved effective addressing various aspects ms pathogenesis vitro vivo models given latest clinical trials proving pde4 inhibitor ibudilast exerts neuroprotective effects patients progressive ms research field intensified selective pde4 inhibitors enhanced safety features seriously considered prospective complementary ms therapypmid33655851 doi102174 1381612827666210303142356,1.0
multiple sclerosis subclinical neuropathology healthy individuals familial risk scoping review mri studies neuroimage clin 2021 jun 18 31102734 doi 101016 jnicl2021102734 online ahead printabstractmultiple genetic nonheritable factors linked risk multiple sclerosis ms factors seem contribute disease pathogenesis onset clinical symptoms suggested incidental mri evidence subclinical ms neuropathology individuals without clinical symptoms individuals high familial risk ms firstdegree relatives patients ms can studied mri characterize neuropathology subclinical period ms 16 studies published english performed brain mri healthy individuals high familial risk ms included scoping review studies suggest either conclusive 5 inconclusive yet considerable 4 conclusive evidence 7 incidence subclinical neuropathology including focal diffuse tissue damage across studies white matter lesions fulfilling ms criteria observed 86 613 individuals 14 future research needed evaluate longitudinal dynamics clinical relevance preclinical imaging abnormalities mspmid34171607 doi101016 jnicl2021102734,0.0
telephonebased assessment multiple sclerosis patients ain shams university hospital coronavirus disease 2019 pandemic egypt j neurol psychiatr neurosurg 2021 57 1 66 doi 101186 s41983021003161 epub 2021 may 30abstractbackground assessment multiple sclerosis ms patients era coronavirus disease 2019 covid19 pandemic confronted overwhelmed healthcare facilities egypt fear patients get infected attending followup visits study aimed assess value telephonebased assessments followup ms patients includes one hundred five patients participated study completed 3 telephonebased assessments hauser ambulation index multiple sclerosis neuropsychology questionnaire msnq symptoms multiple sclerosis scale smss results hauser ambulation index significantly correlated latest expanded disability status scale edss score done within 1 month telephone call r0738 p0001 analysis msnq scores showed onethird study population evidence cognitive neuropsychological impairment post hoc analysis regarding cognitive psychological impairment component smss revealed patients answered never significantly lower msnq scores compared answered sometimes p0016 often p0022 always p0001 comparison edss scores patients regarding sensorymotor impairment component smss showed nonsignificant differenceconclusion hauser ambulation index may reliable telephonebased tool assessment physical disability msnq cognitive psychological impairment component smss can used assessment cognitive psychological impairment among patients mspmid34093002 pmcpmc8164886 doi101186 s41983021003161,0.0
prognostic value cerebrospinal fluid glutamate multiple sclerosis medicina b aires 2021 81 5 774779abstractthe objective study evaluate association glutamate glu levels cerebrospinal fluid csf disease onset disease progression follow cohort multiple sclerosis ms patients glu level measured disease onset first relapse mri obtained baseline followup every 12 months determine percent brain volume change pbvc cortical thickness ct t2 lesion volume t2lv primary predictors interest baseline csf glu levels pbvc ct well clinical disease progression measured expanded disability status scale edss annualized relapse rate followup total 26 ms patients included mean concentration glu csf diagnosis 53 04 um l significant association observed higher baseline levels glu increase edss follow b 106 95ci 047166 p 0003 well pbvc b 071 95ci 056138 p 0002 ct b 015 95ci 006033 p 001 observe association baseline glu levels relapse rate t2lv followup b 008 95ci 011043 p 011 b 195 95ci 39330 p 022 respectively higher glu concentrations disease onset associated increase pbvc edss progression followup ms patientspmid34633951,0.0
relayed nuclear overhauser effect weighted rnoew imaging identifies multiple sclerosis neuroimage clin 2021 oct 28 32102867 doi 101016 jnicl2021102867 online ahead printabstractmultiple sclerosis ms autoimmune disease central nervous system immune system attacks myelin axons consequently leading demyelination axonal injury magnetic resonance imaging mri plays pivotal role diagnosis ms currently various types mri techniques used detect pathology ms based unique mechanisms study applied relayed nuclear overhauser effect weighted rnoew imaging study human ms clinical 3t three groups subjects including 20 normal control nc subjects 14 neuromyelitis optica spectrum disorders nmosd patients 21 ms patients examined clinical 3t mri scanner wholebrain rnoew images subject obtained acquiring control labeled image within four minutes significantly lower brain rnoew contrast detected ms group compared nc p 0008 nmosd p 0014 groups significant difference found nc nmosd groups p 0939 lower rnoew contrast ms group compared nc nmosd group significant white matter p 0041 0021 gray matter p 0004 0020 brain parenchyma p 0015 0021 moreover ms lesions showed higher number larger size lower rnoew contrast nmosd lesions p 0002 proposed rnoew imaging scheme potential serve new method assisting ms diagnosis importantly may used identify ms nmosdpmid34751151 doi101016 jnicl2021102867,1.0
change learning memory partially mediates effects compensatory cognitive training selfreported cognitive symptoms j head trauma rehabil 2021 feb 22 doi 101097 htr0000000000000662 online ahead printabstractobjective examine associations among compensatory cognitive training cct objective cognitive functioning selfreported cognitive symptoms examined whether change objective cognitive functioning associated participation cct 10week followup mediates change selfreported cognitive symptoms associated cct 15week followupsetting three va outpatient mental health clinicsparticipants veterans history mild traumatic brain injury reported cognitive deficitsdesign randomized controlled trial post hoc causal mediation analysismain measures selfreported cognitive symptoms measured prospectiveretrospective memory questionnaire multiple sclerosis neuropsychological screening questionnaire objective cognitive functioning measured using battery neuropsychological testsresults improvement hopkins verbal learning testrevised hvltr delayed recall test mediated association participation cct decrease prospectiveretrospective memory questionnaire total score improvement hvltr total recall hvltr delayed recall tests meditated association participation cct decrease multiple sclerosis neuropsychological screening questionnaire total score measures objective cognitive functioning significant mediatorsconclusion patients perceptions cognitive symptom improvement due cct partially mediated learning memory though subjective improvements occur regardless changes objective cognitive functioning associated cctpmid33656484 doi101097 htr0000000000000662,0.0
role asic1a epilepsy potential therapeutic target curr neuropharmacol 2021 apr 1 doi 102174 1570159x19666210402102232 online ahead printabstractbackground epilepsy represents one common brain diseases among humans tissue acidosis common phenomenon epileptogenic foci said roles epileptogenesis remain unclear acidsensing ion channel1a asic1a represents potential way assess new therapies asic1a mainly expressed mammalian brain type proteingated cation channel shown play important role pathological mechanism various diseases including stroke epilepsy multiple sclerosismethods data collected web science medline pubmed searching keywords acidsensing ion channels 1a asic1a epilepsy seizureresults role asic1a epilepsy remains controversial may represent promising therapeutic target epilepsyconclusion review intended provide overview structure trafficking molecular mechanisms asic1a order elucidate role asic1a epilepsypmid33797385 doi102174 1570159x19666210402102232,0.0
bloodcerebrospinal fluid csf barrier dysfunction means reduced csf flow barrier leakage conclusions csf protein data arq neuropsiquiatr 2021 jan 79 1 5667 doi 101590 0004282xanp20200094abstractbackground increased concentrations serum proteins cerebrospinal fluid csf interpreted bloodcsf barrier dysfunction frequently used interpretations barrier leakage disruption breakdown contradict csf protein data suggest reduced csf flow rate causeresults even severest barrier dysfunctions change molecular sizedependent selectivity interindividual variation protein transfer across barriers serum protein concentrations lumbar csf increase hyperbolic functions levels proteins pass barrier remain constant brain proteins increase linearly leptomeningal proteins csf protein dynamics lumbar blockade can also explained independent barrier passage reduced caudally directed flow local accumulation gadolinium multiple sclerosis ms now understood due reduced bulk flow elimination interstitial fluid isf nonlinear change steady state barrier dysfunction along normal rostrocaudal gradients supports diffusion flow model contradicts obstructions diffusion pathways regardless cause disease pathophysiological flow blockages found bacterial meningitis leukemia meningeal carcinomatosis guillainbarr syndrome ms experimental allergic encephalomyelitis humans fortyfold higher albumin concentrations early fetal development decrease later maturation arachnoid villi ie beginning csf outflow contradicts relevant outflow lymphatic system respiration heartbeatdependent oscillations disturb net direction csf flowconclusion bloodcsf bloodbrain barrier dysfunctions expression reduced csf isf flow ratepmid33656113 doi101590 0004282xanp20200094,0.0
prevalence latent tuberculosis multiple sclerosis clinic effect multiple sclerosis treatment tuberculosis testing int j ms care 2021 janfeb 23 1 2630 doi 107224 153720732019015 epub 2020 apr 14abstractbackground patients compromised immune system risk converting latent tuberculosis infection ltbi active tuberculosis tb infection multiple sclerosis ms therapies may put individuals ltbi higher risk tbmethods patients beth israel deaconess medical center ms clinic screened tb part routine testing quantiferontb gold intube qftgit assay cellestis ltd 2013 2017 patients tested either immunomodulatory therapyresults four 222 patients 18 95 ci 0136 positive qftgit results three patients risk factors tb emigrated tbendemic countries worked health care industry twentyeight 222 patients 126 indeterminate assay result 750 occurred patients taking dimethyl fumarate fingolimod natalizumab anticd20 treatments showed 0 77 indeterminate resultsconclusions prevalence ltbi 18 beth israel deaconess medical center ms clinic ltbi cases associated known risk factors tb screening ltbi starting immunosuppressive agents ms help prevent activation tb dimethyl fumarate use associated indeterminate qftgit results possibly due functional effects lymphocytes levels cytokines interferon gamma contrast fingolimod use rarely associated indeterminate qftgit results despite high rate lymphopenia virtually patientspmid33658903 pmcpmc7906031 doi107224 153720732019015,0.0
role prolactin central nervous system inflammation rev neurosci 2021 jan 1 doi 101515 revneuro20200082 online ahead printabstractprolactin shown favor activation suppression microglia astrocytes well release inflammatory antiinflammatory cytokines prolactin also associated neuronal damage diseases multiple sclerosis epilepsy experimental models diseases however studies show prolactin neuroprotective effects conditions neuronal damage inflammation may used neuroprotector factor review first discuss general information prolactin summarize recent findings prolactin function inflammatory antiinflammatory processes factors involved possible dual role prolactin described finally review function prolactin specifically central nervous system promotes neuroprotective effect neuronal damage particularly experimental autoimmune encephalomyelitis excitotoxicity overall studies indicated prolactin may promising molecule treatment neurological diseasespmid33661585 doi101515 revneuro20200082,1.0
risk multiple sclerosis analysis interactions variants nuclear mitochondrial genomes mol biol mosk 2021 novdec 55 6 956964 doi 1031857 s0026898421060070abstractthere increasing evidence interaction mitochondrial nuclear genomes substantially affects risk neurodegenerative diseases role mitonuclear interactions development multiple sclerosis severe chronic neurodegenerative disease polygenic nature poorly understood work analyzed association multiple sclerosis twocomponent mitonuclear combinations include seven polymorphic variants nuclear genome localized region ucp2 kif1b genes pvt1 locus myc pvt1 mir1208 genes often polymorphisms mitochondrial genome well individual genetic variants make combinations association individual components combinations multiple sclerosis also evaluated 507 patients multiple sclerosis 321 healthy individuals enrolled study participants ethnic russians two mitonuclear combinations associated multiple sclerosis identified ucp2 rs660339 + mtatp6 rs193303045 g combination characterized pvalue 0015 139 95 ci 105187 pvt1 rs2114358 g + mtnd1 rs1599988 combination pvalue 0012 177 95 ci 110284 one individual components combinations allele rs660339a nuclear gene ucp2 encoding uncoupling protein 2 mitochondrial anion carrier family independently associated multiple sclerosis p 0028 136 95 ci 101184 study expands current understanding role mitonuclear interactions variance nuclear genes whose products function mitochondria risk mspmid34837699 doi1031857 s0026898421060070,0.0
emerging role cannabinoids synthetic cannabinoid receptor 1 cannabinoid receptor 2 receptor agonists cancer treatment chemotherapyassociated cancer management j cancer res ther 2021 janmar 17 1 19 doi 104103 jcrtjcrt_488_18abstractcannabis extensively utilized medicinal properties till 19th century steep decline medicinal usage observed later due emergence illegal recreational drug advances technology scientific findings led discovery delta9tetrahydrocannabinol thc primary psychoactive compound cannabis led discovery endogenous cannabinoids system consisting gproteincoupled receptors cannabinoid receptor 1 cannabinoid receptor 2 along ligands mainly anandamide 2arachidonoylglycerol endocannabinoid ec shown modulator physiological functions also immune system endocrine network central nervous system medicinal research metadata analysis last decades shown significant potential thc cannabidiol cbd exert palliative effects people suffering many forms advanced stages cancers undergo chemotherapyinduced nausea vomiting followed severe chronic neuropathic pain weight loss thc cbd exhibit effective analgesic anxiolytic appetitestimulating effect patients suffering cancer drugs currently available market treat chemotherapyinduced cancerrelated ailments sativex gw pharmaceutical dronabinol unimed pharmaceuticals nabilone valeant pharmaceuticals apart exerting palliative effects thc also shows promising role treatment cancer growth neurodegenerative diseases multiple sclerosis alzheimers disease alcohol addiction hence exploited potential benefits current review discusses nature role cb receptors specific applications cannabinoids major studies assessed role cannabinoids cancer managementpmid33723124 doi104103 jcrtjcrt_488_18,0.0
immunomodulation cannabinoids current uses mechanisms identification data gaps addressed additional therapeutic application adv pharmacol 2021 91159 doi 101016 bsapha202101001 epub 2021 mar 12abstractthe endocannabinoid system plays critical role immunity therefore components including cannabinoid receptors 1 2 cb1 cb2 putative druggable targets immunemediated diseases whether modulating endogenous cannabinoid levels interacting cb1 cb2 receptors directly cannabinoids cannabinoidbased therapeutics cbts show promise antiinflammatory immune suppressive agents herein provide overview cannabinoid effects animals humans provide support use cbts immunemediated disease multiple sclerosis ms inflammatory bowel disease ibd asthma arthritis diabetes human immunodeficiency virus hiv hivassociated neurocognitive disorder hand exhaustive review cannabinoid effects immune responses rather provides 1 key studies initial novel observations made animal studies 2 critical human studies including metaanalyses randomized clinical trials rcts cbts assessed 3 evidence role cb1 cb2 receptors immunemediated diseases genetic analyses single nucleotide polymorphisms snps cnr1 cnr2 genes encode cb1 cb2 receptors respectively perhaps importantly provide view data gaps exist addressed allow rigorous evaluation efficacy risk benefit ratio use cannabinoids cbts immunemediated diseasespmid34099105 doi101016 bsapha202101001,0.0
utility magnetoencephalography multiple sclerosis systematic review neuroimage clin 2021 sep 9 32102814 doi 101016 jnicl2021102814 online ahead printabstractintroduction magnetoencephalography meg allows high degree temporal spatial accuracy recording cortical oscillatory activity evoked fields date review undertaken synthesise meg studies multiple sclerosis ms undertook systematic review utility meg msmethods identified meg studies carried ms using embase medline cochrane trip psychinfo databases included original research articles cohort minimum five multiple sclerosis patients quantifying least one meg parameter used modified version jbi mjbi casecontrol studies assess risk biasresults identified 30 studies 13 centres involving least 433 ms patients 347 controls found evidence meg shows perturbed activity commonly reduced power modulations reduced connectivity association altered clinical function multiple sclerosis specific replicated findings decreased motor induced responses beta band diminished increase gamma power visual stimulation increased latency reduced connectivity somatosensory evoked fields association upper alpha connectivity cognitive measures people ms overall studies moderate quality mean mjbi score 67 discussion find evidence utility meg multiple sclerosis eventrelated designs particular value show replicability centres stage clear whether changes specific multiple sclerosis also observable diseases studies look explore cognitive control depth using intask designs undertake longitudinal studies determine whether changes prognostic valuepmid34537682 doi101016 jnicl2021102814,0.0
relationship neutrophil lymphocyte ratio uric acid levels multiple sclerosis patients bratisl lek listy 2021 122 5 357361 doi 104149 bll_2021_060abstractbackground study aimed determine whether neutrophil lymphocyte ratio nlr obtained dividing number neutrophils number lymphocytes uric acid ua levels multiple sclerosis ms patients vary compared healthy controls establish correlations among changes well changes ms subtypes immunomodulatory drug use duration disease prognosismethods 150 patients presented hospital diagnosed ms 150 healthy volunteers retrospectively included study edss score expanded disability status scale used assess disability patientsresults compared healthy volunteers ms patients lower ua levels p 0001 higher nlr values p 002 addition ua levels higher patients low edss score immunomodulating drugs p 0001 p 004 respectively nlr value lower patients low edss score p 0001 negative correlation nlr value ua r 023 p 0003 similarly ua level decreased increasing edss score duration disease r 038 p 0001 r 017 p 002 respectively conclusion evaluating nlr value recognized new marker inflammation ms together ua value thought protective ms might effective evaluating parameters alone demonstrating disability patients tab 4 ref 28 text pdf wwwelissk keywords neutrophil lymphocyte ratio uric acid multiple sclerosis inflammation expanded disability status scalepmid33848187 doi104149 bll_2021_060,0.0
characteristics outcome biopsyproven malignant hypertension severe kidney injury retrospective study indian j nephrol 2021 sepoct 31 5 467473 doi 104103 ijnijn_187_20 epub 2021 apr 10abstractbackground although malignant hypertension begets multiple target organ damage limited data patients severe renal injury evident malignant hypertension renal histopathologymethods assessed baseline demographic histopathological findings clinical outcomes retrospective analysis patients biopsyproven malignant hypertensionresults thirty cases analysed mean age patients 40 115 years 28 933 males average systolic diastolic blood pressures hospitalisation 19704 2414 11741 1831 mmhg respectively severe retinopathy seen 10 333 median egfr admission 63 iqr 44915 ml min 21 724 needed dialysis nine 30 cases glomerular crescents primary glomerular disease 7 igan 1 c3 glomerulonephritis 1 membranoproliferative glomerulonephritis 17 566 thrombotic microangiopathy threemonth esrd free survival 345 n 10 esrd cohort incidence dialysis requiring kidney injury presentation 944 vs 40 nonesrd cohort patient survival 1 year 50 isolated malignant hypertension differed others regard lesser incidence severe retinopathy less glomerular sclerosis 2961 1586 vs 4845 3078 p 003 absence crescents p 002 incidence tuft wrinkling 100 vs 35 p 000 total vessel occlusion p 002 conclusion clinicopathologically accelerated essential hypertension differs hypertension glomerular disease degree kidney injury presentation risk predictor longterm morbidity malignant hypertensionpmid34880557 pmcpmc8597798 doi104103 ijnijn_187_20,0.0
acute acalculous cholecystitis multiple sclerosis patient treated natalizumab neurol india 2021 marapr 69 2 495496 doi 104103 00283886314544abstractnatalizumab diseasemodifying drug proved greatly effective welltolerated highlyactive multiple sclerosis ms however may increase risk opportunistic infections viral ones describe 37yearold woman treated natalizumab relapsingremitting multiple sclerosis rrms presented clinic malaise arthromyalgias rash fever later developed diarrhea severe abdominal pain diagnosis parvovirus b19 b19v infection acute acalculous cholecystitis aac eventually made knowledge first reported case aac possibly related natalizumab therapy b19v infectionpmid33904486 doi104103 00283886314544,0.0
multiple koenen tumors rare entity combination treatment 1 topical sirolimus electrofulguration excision skin appendage disord 2021 jan 7 1 6670 doi 101159 000511743 epub 2020 dec 16abstractintroduction koenen tumors benign cutaneous manifestations tuberous sclerosis disfiguring painful challenging treat frequently recur report case longstanding multiple koenen tumors affecting twenty nails elderly female successfully treated combination topical sirolimus 1 surgical excision electrofulgurationcase report 57yearold lady presented multiple asymptomatic periungual subungual tumors affecting twenty nails since 27 years cutaneous examination revealed confetti macules ashleaf macule shagreen patch trunk nail biopsy compatible koenens tumor computerized tomography brain showed diffuse patchy sclerosis tumors treated topical sirolimus 1 ointment 10 months excellent regression electrofulguration great toenails surgical excision right thumbnail periungual fibroma done 1 sirolimus advised surgical treatment adverse effects recurrence tumors 2year followupdiscussion topical sirolimus 1 effective tumor regression preventing new tumor formation larger tumors interfered daily chores treated excision electrofulguration thus combination treatment rare presentation tuberous sclerosis provided optimum resultspmid33614724 pmcpmc7879313 doi101159 000511743,0.0
fasudil ameliorates cognitive deficits oxidative stress neuronal apoptosis via inhibiting rock mapk activating nrf2 signalling pathways app ps1 mice folia neuropathol 2021 59 1 3249 doi 105114 fn2021105130abstractalzheimers disease ad severe neurodegenerative disorder central nervous system cns characterized neuron loss dementia previous abundant evidence demonstrates first critical step course ad state oxidative stress neuronal loss closely related interaction several signalling pathways neuroprotective efficacy rhoassociated protein kinase rock inhibitor treatment ad reported exact mechanism well elucidated purpose study investigate therapeutic effects fasudil amyloid precursor protein presenilin1 app ps1 mice discover potential underlying mechanism sixteen 8monthold app ps1 mice divided model fasudil treatment groups 8 wildtype mice used normal control group behavioural test mice sacrificed immunofluorescence biochemical tests results showed administration fasudil improved learning memory ability elevated concentration antioxidative substances decreased lipid peroxides well inhibited neuronal apoptosis increasing expression bcell lymphoma2 bcl2 p 005 reducing bcl2 associated x bax p 005 cleaved caspase3 p 005 app ps1 mice moreover fasudil treatment also ameliorated phosphorylation p38 p 001 cjun nterminal kinase jnk p 0001 extracellular regulated protein kinases erk p 0001 accelerated nuclear factorerythroid 2 p45related factor 2 nrf2 p 001 expression antioxidative downstream molecules p 005 p 005 p 005 respectively data present study demonstrate fasudil significantly restored cognitive function restrained oxidative stress reduced neuronal apoptosis hippocampus probably inhibiting rock mapk activating nrf2 signalling pathways app ps1 micepmid33969676 doi105114 fn2021105130,1.0
implications suboptimal year1 outcomes diseasemodifying therapy employees multiple sclerosis j med econ 2021 mar 191 doi 101080 1369699820211906013 online ahead printabstractaim multiple sclerosis ms poses substantial employer burden medically related absenteeism disability costs due chronic debilitating nature diseasealthough previous studies evaluated relapse nonadherence discontinuation switching individually little known overall collective prevalence implications employees ms treated diseasemodifying therapies dmts study evaluated proportion employees ms suboptimal dmt year1 outcomes quantify clinical economic burden suboptimal year1 outcomes us employer perspectivematerials methods employees ms selected workpartners database eligibility criteria 2 ms diagnosis claims icd9cm 340xx icd10cm g35 1 1 20103 31 2019 1 twicedaily oral selfinjectable dmt claim first claim index continuous eligibility 6months pre 1year postindex baseline dmt age 1864 years suboptimal year1 outcomes included nonadherence proportion days covered 80 discontinuation gap 60 days switch relapse msrelated hospitalization emergency room visit outpatient visit corticosteroid twopart logisticgeneralized linear model evaluated costsresults 488 eligible patients half n 247 506 suboptimal year1 outcomes 395 nonadherence 98 discontinuation 109 switching 207 relapse mutually exclusive employees suboptimal year1 outcomes higher allcause medical 12 730 vs 6428 p 00001 msrelated medical 5444 vs 2652 p 00001 nondmt pharmacy 2920 vs 2169 p 00199 sick leave 1247 vs 908 p 00274 shortterm disability 934 vs 146 p 00001 costs longterm disability 751 vs 0 p 01250 workers compensation 56 vs 24 p 01276 significantly differlimitations administrative claims lack clinical information results may generalizable patients care settingsconclusions half employees ms sample suboptimal year1 outcomes ie nonadherence discontinuation switching relapse suboptimal year1 outcomes associated greater medical sick leave shortterm disability costspmid33739915 doi101080 1369699820211906013,0.0
longterm effectiveness fingolimod multiple sclerosis realworld clinical setting eur neurol 2021 apr 716 doi 101159 000514828 online ahead printabstractintroduction primary aim present study evaluate longterm efficacy fingolimod patients multiple sclerosis ms secondary aims describe safety fingolimod evaluation treatment satisfaction impact quality life real lifemethods collected clinical demographical neuroradiological treatment data including pre posttreatment status healthrelated quality life 286 ms patients consecutively treated fingolimod clinical assessment based expanded disability status scale edss quality life assessment performed msrelated quality life inventory msqoli data recorded baseline every 6 months 2 yearsresults one hundred fourteen males 172 females enrolled annualized relapse rate edss showed statistically significant reduction observation period p 0001 patients also demonstrated substantial improvements magnetic resonance imaging mri outcomes p 0001 healthrelated quality life scores improved significantly baseline 24month visit p 0001 serious adverse events occurredconclusion cohort fingolimod treatment associated reduced relapse mri activity improved edss msqoli scores additionally fingolimod able maintain effectiveness considerable long period treatmentpmid33827097 doi101159 000514828,0.0
potential preventive effect pregnancy breastfeeding multiple sclerosis eur neurol 2021 mar 19114 doi 101159 000514432 online ahead printabstractbackground multiple sclerosis ms inflammatory demyelinating chronic neurological disease affects central nervous system young adults quality life several studies investigated effects pregnancy breastfeeding ms however evidence regarding influence pregnancy breastfeeding ms still accumulating review aimed summarize current evidence regarding effects pregnancy breastfeeding mssummary systematic electronic literature search pubmed embase databases conducted determine relevant published articles eligible studies summarized evaluated tables key messages majority studies indicated pregnancy appears lower rate ms relapses particularly third trimester evidence regarding effect breastfeeding ms remains inconsistent despite reports negative obstetric outcomes pregnant women ms pregnancies women ms categorized highrisk pregnanciespmid33744881 doi101159 000514432,1.0
stem cell therapy dermatology indian j dermatol venereol leprol 2021 jun 24115 doi 1025259 ijdvl_19_20 online ahead printabstractstem cells precursor cells present many tissues ability differentiate various types cells interesting property plasticity can therapeutic implications substantial research field last decades result stem cell therapy now used therapeutic modality many conditions made way dermatology stem cells can classified basis source differentiating capacity skin present interfollicular epidermis hair follicle dermis adipose tissue help maintaining normal skin homeostasis repair regeneration injury view unique properties employed treatment several dermatoses including systemic sclerosis systemic lupus erythematosus scleromyxedema alopecia merkel cell carcinoma pemphigus vulgaris psoriasis wound healing epidermolysis bullosa even aesthetic medicine variable success advent stem cell therapy undoubtedly brought us closer curative treatment disorders previously considered untreatable nevertheless multiple lacunae need addressed including ideal patient selection timing intervention appropriate conditioning regimens postintervention care cost effectiveness research aspects help optimize results stem cell therapypmid34245532 doi1025259 ijdvl_19_20,0.0
treatment women multiple sclerosis planning pregnancy curr treat options neurol 2021 23 4 11 doi 101007 s11940021006664 epub 2021 mar 30abstractpurpose review review data available treatment multiple sclerosis ms pregnancy present recent data diseasemodifying therapies dmt pregnancy breastfeeding treatment recommendationsrecent findings observational data support safety injectable dmts glatiramer acetate interferonbeta use pregnancy oral dmts might associated fetal risk monoclonal antibodies mabs pregnancy rituximab natalizumab likely pose significant fetal risks can cross placenta neonatal hematological abnormalities given second trimester later breastfeeding associated decreased risk postpartum relapses finally injectables mabs likely low transfer breastmilksummary many women ms require dmts pregnancy although injectables continued women highly active ms celldepleting therapies given conception natalizumab continued pregnancy monitoring fetus women encouraged breastfeed higher relapse risk consider injectables mabs breastfeeding data safety dmts around pregnancy needed maximizing function nonpharmacologic approaches complementary dmts special considerations pregnancy dmts covid19 pandemic neededpmid33814892 pmcpmc8008016 doi101007 s11940021006664,0.0
dialogue neuroinflammation neurodegenerative diseases covid19 j environ pathol toxicol oncol 2021 40 3 3749 doi 101615 jenvironpatholtoxicoloncol2021038365abstractit now almost year since emergence deadly sarscov2 millions people losing lives due resultant covid19 apart wellknown consequences respiratory illnesses even effortlessly mapped nervous system routes like blood csf neurons olfactory cells interestingly interaction sarscov2 nervous system cells like neurons microglia astrocytes factor worsen covid19 neuroinflammatory actions release cytokines due astrocyte microglial activation progress towards anticipated cytokine storm proving detrimental management covid19 hyperinflammatory conditions make bbb vulnerable encouraging excessive viral particles cns leading neurodegenerative pathologies like alzheimers disease parkinsons disease creutzfeldtjakob disease multiple sclerosis excessive neuroinflammation neurodegeneration anticipated root causes multiple conditions also essential look factors synergistically enhance worsening diseases covid19 patients additional studies essentialpmid34587403 doi101615 jenvironpatholtoxicoloncol2021038365,0.0
vla4 central target modulating neuroinflammatory disorders neuroimmunomodulation 2021 sep 219 doi 101159 000518721 online ahead printabstractthe complex steps leading central nervous system cns inflammation progress neuroinflammatory neurodegenerative disorders opened new research intervention avenues review focuses therapeutic targeting vla4 integrin discuss clearcut effect immune cell trafficking brain tissues besides explore possibility blocking vla4 may relevant impact nonmigratory activities immune cells antigen presentation tcell differentiation neuroinflammatory process lastly recent refinement computational techniques highlighted way increase specificity reduce detrimental side effects vla4 immunotherapies aiming developing better clinical interventionspmid34515173 doi101159 000518721,0.0
safety feasibility efficacy eccentric exercise intervention people multiple sclerosis ankle contractures int j ms care 2021 janfeb 23 1 3136 doi 107224 153720732019022 epub 2020 mar 6abstractbackground primary aim study investigate safety feasibility eccentric exercise program people multiple sclerosis ms ankle contractures ie reduced ankle range motion rom secondary aims explore efficacy eccentric exercise ankle joint rom functional mobilitymethods five adults ms ankle contractures three women two men mean sd age 508 94 ms duration 76 56 years completed two eccentric exercise training sessions 1045 minutes per week 12 weeks training involved walking backward downhill inclined treadmill gradient 1014 selfselected pace intervention assessed safety adverse events feasibility recruitment rates adherence rates enjoyment levels difficulty discomfort clinical outcomes including passive active ankle rom distance walked 6 minutesresults adverse events eccentric exercise training 100 adherence rate participants enjoyed training experienced low levels muscle soreness discomfort training program improved passive active ankle rom participants however improvements translate improvements walking participantsconclusions walking backward downhill safe feasible training modality people ms ankle contractures clinical outcomes greater passive active ankle rom eccentric exercise training evident however translation clinically meaningful changes walking function requires examinationpmid33658904 pmcpmc7906030 doi107224 153720732019022,0.0
evaluating role hla drb1 alleles oligoclonal bands influencing clinical course multiple sclerosis study mangalore demyelinating disease registry ann indian acad neurol 2021 mayjun 24 3 356360 doi 104103 aianaian_508_20 epub 2021 jan 11abstractbackground possible interaction genetic immunological factors influencing clinical course multiple sclerosis ms studied previously indian populationaim study evaluated association hla alleles ocb affecting clinical course disability msmethods clinical demographic features 145 ms patients csf oligoclonal bands ocb tested isoelectric focussing technique analyzed disability status estimated hla drb1 alleles genotypedresults ocbs positive 538 78 145 ms cases patients csf ocb frequent relapses association hla drb115 early disease onset high annualized relapse rate associated hla drb103 allele relapsing remitting course ms seen hla drb103 15 progressive disease associated drb101 presence ocb hla drb113 significantly associated disability cohortconclusion results study suggest interaction immunological genetic factors may influence disease onset course disability mspmid34446997 pmcpmc8370157 doi104103 aianaian_508_20,1.0
estimation validation ratiobased conditional average treatment effects using observational data j stat assoc 2021 116 533 335352 doi 101080 0162145920201772080 epub 2020 jul 7abstractwhile sample sizes randomized clinical trials large enough estimate average treatment effect well often insufficient estimation treatmentcovariate interactions critical studying datadriven precision medicine observational data real world practice may play important role alleviating problem one common approach trials predict outcome interest separate regression models treatment arm estimate treatment effect based contrast predictions unfortunately simple approach may induce spurious treatmentcovariate interaction observational studies regression model misspecified motivated need modeling number relapses multiple sclerosis patients ratio relapse rates natural choice treatment effect propose estimate conditional average treatment effect cate ratio expected potential outcomes derive doubly robust estimator cate semiparametric model treatmentcovariate interactions also provide validation procedure check quality estimator independent sample conduct simulations demonstrate finite sample performance proposed methods illustrate advantages real data examining treatment effect dimethyl fumarate compared teriflunomide multiple sclerosis patientspmid33767517 pmcpmc7985957 doi101080 0162145920201772080,0.0
direct indirect effects microbiotaderived metabolites neuroinflammation multiple sclerosis microbes infect 2021 mar 25104814 doi 101016 jmicinf2021104814 online ahead printabstractmultiple sclerosis ms experimental autoimmune encephalomyelitis eae highly influenced changes microbiota microbiotaderived metabolites including short chain fatty acids bile acids tryptophan derivatives review will discuss effects microbiotaderived metabolites neuroinflammation driven central nervous systemresident cells peripheral immune cells influence outcomes eae mspmid33775860 doi101016 jmicinf2021104814,0.0
prospect dopaminergic therapy multiple sclerosis zh nevrol psikhiatr im s s korsakova 2021 121 2 6770 doi 1017116 jnevro202112102167abstractdopamine direct mediator neuroimmune interactions recent studies show acting dopaminergic receptors possible modulate th17immune response play crucial role pathogenesis multiple sclerosis dopamine can modulate th17 cells function well dendritic cellmediated th17immune response allows considering dopaminergic receptors new therapeutic target multiple sclerosis short communication prospects using dopaminergic therapy pathogenetic treatment multiple sclerosis discussedpmid33728853 doi1017116 jnevro202112102167,0.0
multiple sclerosis patients covid19 egypt j neurol psychiatr neurosurg 2021 57 1 43 doi 101186 s41983021002873 epub 2021 mar 23abstractcoronavirus disease 2019 covid19 now major issue fields medicine due higher mortality rate among patients chronic diseases also caused concern patients multiple sclerosis ms addition often receiving immunosuppressive drugs aim article discuss currently known severity covid19 ms patientspmid33776407 pmcpmc7985914 doi101186 s41983021002873,0.0
immunoregulatory effects tolerogenic probiotics multiple sclerosis adv exp med biol 2021 128687105 doi 101007 9783030550356_6abstractgut microbiota essential roles prevention progression multiple sclerosis ms association gut microbiota central nervous system cns immune system response ms patients documented many studies composition gut microbiota lead sensitization resistance promotion development ms disease probiotics major part gut microflorapopulation substituted tolerogenic probiotics protect cns autoimmune responses tolerogenic probiotics antiinflammatory immunomodulatory properties effects intestinal flora can reestablish regulatory mucosal systemic immune responses probiotics able prevent restore excessive activation inflammatory responses especially autoreactive t cells inflammatory cytokines tolerogenic probiotics induction regulatory t cells increase antiinflammatory cytokines play crucial role controlling inflammation maintaining tolerance hemostasis therefore probiotics can considered preventive therapeutic tool ms present review focus immunoregulatory effects tolerogenic probiotics severity disease well th1 th2 treg populations different experimental human studies mspmid33725347 doi101007 9783030550356_6,0.0
employment status monitoring argentinian population patients multiple sclerosis particularities developing country work 2021 apr 7 doi 103233 wor213442 online ahead printabstractbackground multiple sclerosis ms neurological chronic disease causes number physical cognitive emotional symptoms identification factors will allow mitigating unemployment improve quality life patients buffalo vocational monitoring survey bvms tool characterize workchallenged patientsobjective describe analyze bvms data people multiple sclerosis pwms argentina study association physical cognitive psychiatric morbidity employed patients comparing performance ms workchallenged ms workstable patients without accommodationsmethods 119 ms patients administered argentina adaptation bvms completed measures physical disability fatigue depression cognitive processing speed memory verbal fluencyresults 5714of patients employed 1932were unemployed remaining roles housewife students disability retirees within employed subgroup 6026 working employees 3974 selfemployed cognitive clinical variables differentiate patients without negative events accommodations p 005 conclusions spanish version bvms considered new tool monitor employment difficulties spanishspeaking ms patients ms workchallenged higher depression fatigue worse performance cognitive variablespmid33843718 doi103233 wor213442,0.0
gut microbiota immunity autoimmune diseases rinsho ketsueki 2021 62 8 900908 doi 1011406 rinketsu62900abstracta huge number indigenous commensal bacteria reside intestines humans animals however host animals unconditionally accept gut microbiota order contain gut microbiota secreting immunoglobulin intestine equipped intestinal immune system literally largest peripheral lymphoid tissue body 60 70 peripheral immune cells accumulated hand gut microbiota greatly impact host physiology pathology normal development host immune system relies interaction gut microbiota addition abnormal gut microbiota dysbiosis known associated various disease statuses including autoimmune diseases understanding causal relationship pathophysiology diseases dysbiosis still limited verification experiments using animal models clarifying gut microbiota important regulatory factor pathogenesis progression diseasespmid34497229 doi1011406 rinketsu62900,0.0
pharmacological approaches studying potassium channels handb exp pharmacol 2021 jul 1 doi 101007 164_2021_502 online ahead printabstractin review consider pharmacology potassium channels perspective channels therapeutic targets firstly describe three main families potassium channels humans disease states implicated secondly describe existing therapeutic agents act potassium channels outline channels represent underexploited therapeutic target potential future drug development thirdly consider evidence desired order embark drug discovery programme targeting particular potassium channel chosen two case studies activators twopore domain potassium k2p channel trek2 k2p101 treatment pain inhibitors voltagegated potassium channel kv13 use autoimmune diseases multiple sclerosis describe evidence base suggest viable therapeutic targets finally detail main technical approaches available characterise pharmacology potassium channels identify novel regulatory compounds draw particular attention comprehensive vitro proarrhythmia assay initiative cipa https cipaprojectorg project cardiac safety example might desirable possible future ion channel regulator discovery projectspmid34195873 doi101007 164_2021_502,0.0
sjogren#39 s syndrome pulmonary disease adv exp med biol 2021 1303193207 doi 101007 9783030630461_12abstractsjogrens syndrome autoimmune connective tissue disease targeting exocrine glands frequently affecting respiratory system pulmonary disease important extraglandular manifestation carries morbidity mortality typically affects small airways ranging mild severe respiratory symptoms upper airways also commonly involved predisposing sinusitis occur frequently normal population lymphocytic interstitial pneumonia initially thought prevailing parenchymal disease however multiple cohorts report noninterstitial pneumonia frequent subtype interstitial lung disease review highresolution computed tomography scans cystic lesions commonly found associate small airways parenchymal disease presence amyloidosis lymphomas considered differential overall sjogrens syndrome higher risk lymphoma lungs condition thought especially images reveal pulmonary nodularity lymphocytic interstitial pneumonia lymphadenopathy although pulmonary artery hypertension traditionally exceptionally linked sjogrens syndrome together systemic lupus erythematosus now acknowledged common pulmonary vascular disease east asian populations even patients systemic sclerosis although controlled prospective trials treat pulmonary disease sjogrens syndrome mainstay treatment modality still falls glucocorticoid therapy systemic inhaled combined immune modulators alone evidence sustains successful outcomes based reported cases case seriespmid33788195 doi101007 9783030630461_12,0.0
pharmacoeconomic aspects using cladribine tablets treatment adult patients remitting multiple sclerosis zh nevrol psikhiatr im s s korsakova 2021 121 8 3036 doi 1017116 jnevro202112108130abstractobjective conduct pharmacoeconomic analysis using cladribine tablets secondline treatment option adult patients highly active remitting multiple sclerosis russiamaterial methods current treatment practice highly active multiple sclerosis natalizumab fingolimod alemtuzumab ocrelizumab considered comparator cladribine tablets clinical economic study conducted using cost minimization method budget impact analysis cost using cladribine tablets compared cost using current treatment practiceresults cladribine tablets costsaving alternative treatment patients highly active multiple sclerosis compared current treatment practice within 4year period direct medical costs reduction 2 million rub 501 per personconclusion case switching patients currently provided disease modifying drugs cladribine 4 years health budget will save 6284 million rub 501 pmid34481433 doi1017116 jnevro202112108130,0.0
herpesviruses biomarkers disseminated encephalomyelitis multiple sclerosis children zh nevrol psikhiatr im s s korsakova 2021 121 3 138145 doi 1017116 jnevro2021121031138abstractthe relevance study demyelinating diseases due increasing frequency children clarification role infectious agents genesis well possibility transformation disseminated encephalomyelitis multiple sclerosis literature review presents currently available information causes development demyelinating diseases biomarkers disseminated encephalomyelitis multiple sclerosis causes unfavorable course possible laboratory parameters indicating transition one disease another can used prognostic factors authors also noted experience authors importance adequate etiopathogenetic therapy changing nature course disease particular confirming relationship frequency exacerbations adem ms activation herpesvirus infections courses specific antiviral therapy effective well pathogenetic therapy aimed correcting endothelial dysfunction using drug cytoflavinpmid33834732 doi1017116 jnevro2021121031138,1.0
cervical thoracic cord atrophy multiple sclerosis phenotypes quantification correlation clinical disability neuroimage clin 2021 30102680 doi 101016 jnicl2021102680 epub 2021 apr 28abstractobjective sought characterize spinal cord atrophy along entire spinal cord major multiple sclerosis ms phenotypes evaluate correlation clinical disabilitymethods axial t1weighted images automatically reformatted point along cord spinal cord crosssectional area sccsa calculated c1t10 vertebral body levels profile plots compared across phenotypes average values c23 c45 t49 regions compared across phenotypes correlated clinical scores categorized atrophic normal based zscores derived controls compare clinical scores subgroups subset relapsingremitting cases longitudinal scans regions compared change clinical scoresresults crosssectional study consisted 149 adults diagnosed relapsingremitting ms rrms 49 secondaryprogressive ms spms 58 primaryprogressive ms ppms 48 controls longitudinal study included 78 rrms cases compared controls ms groups smaller average regions except rrms t49 region ms groups sccsa regions particularly cervical cord correlated clinical measures rrms cohort 22 cases least one atrophic region whereas progressive ms rate almost 70 longitudinal analysis showed correlation clinical disability cervical cord thinningconclusions spinal cord atrophy prevalent across ms phenotypes regional measures rrms cohort progressive cohort including spms ppms correlated disability longitudinal changes spinal cord documented rrms cases making potential marker disease progression cervical sccsa correlated disability progression measures inclusion thoracic measurements improved correlation allowed better subgrouping spinal cord phenotypes cord atrophy important easily obtainable imaging marker clinical subclinical progression ms phenotypes measures can play key role patient selection clinical trialspmid34215150 doi101016 jnicl2021102680,0.0
clinical epidemiological aspects neuromyelitis optic spectrum diseases russian population zh nevrol psikhiatr im s s korsakova 2021 121 7 96103 doi 1017116 jnevro202112107196abstractobjective present clinical epidemiological aspects neuromyelitis optica spectrum disorders nmosd russian federationmaterial methods studied 142 patients met diagnostic criteria 2015 nmosd sex age disease onset presence absence aquaporin4 immunoglobulin g antibodies aqp4igg mail clinical symptoms oligoclonal igg therapy treatment exacerbations prevention exacerbations compliance 2006 diagnostic criteria assessedresults prevalence women 4261 frequent age disease onset 1829 years 36 cases laboratory aspects disease characterized approaches treatment prevention exacerbations nmosd patients russian population evaluated approaches diagnostics compared depending applied diagnostic criteria 34 patients meet neuromyelitis optica 2006 diagnostic criteria prognosis prevalence nmosd russian population proposed 045421 100000conclusion first published data clinical epidemiological characteristics nmosd russian federationpmid34460164 doi1017116 jnevro202112107196,0.0
integration teleneurology within health system manage patients multiple sclerosis cns demyelinating disorders covid19 pandemic ann indian acad neurol 2021 mayjun 24 3 443445 doi 104103 aianaian_457_20 epub 2020 sep 2no abstractpmid34447020 pmcpmc8370152 doi104103 aianaian_457_20,1.0
disruption brainstem monoaminergic fibre tracts multiple sclerosis putative mechanism cognitive fatigue fixelbased analysis neuroimage clin 2021 feb 12 30102587 doi 101016 jnicl2021102587 online ahead printabstractin multiple sclerosis ms monoaminergic systems altered result inflammationdependent reduced synthesis direct structural damage aberrant monoaminergic neurotransmission increasingly considered major contributor fatigue pathophysiology study aimed compare integrity monoaminergic white matter fibre tracts projecting brainstem nuclei group patients ms n 68 healthy controls n 34 investigate association fatigue fibre tracts integrity assessed novel fixelbased analysis simultaneously estimates axonal density means fibre density white matter atrophy means fibre cross section focused ventral tegmental area locus coeruleus raphe nuclei main source dopaminergic noradrenergic serotoninergic fibres within brainstem respectively fourteen tracts interest projecting brainstem nuclei reconstructed using diffusion tractography compared means product fibredensity crosssection fdc finally correlations monoaminergic axonal damage modified fatigue impact scale scores evaluated ms fixelbased analysis revealed significant axonal damage measured fdc reduction within selective monoaminergic fibretracts projecting brainstem nuclei ms patients comparison healthy controls particularly within dopaminergicmesolimbic pathway noradrenergicprojections prefrontal cortex serotoninergicprojections cerebellum moreover observed significant correlations severity cognitive fatigue axonal damage within mesocorticolimbic tracts projecting ventral tegmental area well within locus coeruleus projections prefrontal cortex suggesting potential contribution dopaminergic noradrenergic pathways central fatigue ms findings support hypothesis axonal damage along monoaminergic pathways contributes reduction dysfunction monoamines ms add new information mechanisms monoaminergic systems contribute ms pathogenesis fatigue supports need research monoamines therapeutic targets aiming combat alleviate fatigue mspmid33610097 doi101016 jnicl2021102587,0.0
lmnb1 duplicationmediated autosomal dominant adultonset leukodystrophy indian family ann indian acad neurol 2021 mayjun 24 3 413416 doi 104103 aianaian_1262_20 epub 2021 may 21abstractautosomal dominant leukodystrophy adult onset neurodegenerative disorder presenting progressive symptoms ataxia autonomic dysfunction fourth fifth decade life clinical similarity multiple sclerosis shows characteristic magnetic resonance imaging findings diffuse bilaterally symmetrical leukodystrophy can distinguish disorder rare disorder known treatment till date never described indian subcontinent present indian family autosomal dominant adultonset demyelinating leukodystrophy multiple members affected four generations demonstrate cheap accurate molecular method realtime polymerase chain reaction detect lmnb1 gene duplication genetic basis devastating disorderpmid34447008 pmcpmc8370147 doi104103 aianaian_1262_20,1.0
impact covid19 lockdown quality life chronic neurological diseases results covqolcnd study eur neurol 2021 aug 3110 doi 101159 000517380 online ahead printabstractbackground coronavirus disease 2019 covid19 pandemic lockdown period may induce impairment quality life qol disruption treatment dit posttraumatic stress disorder ptsd chronic neurological diseases cnds reach information multicenter crosssectional study covqolcnd planned parkinsons disease pd headache ha multiple sclerosis ms epilepsy ep polyneuropathy pnp cerebrovascular disease cvd selected cndmethods covqolcnd study includes demographic data world health organization quality life short form whoqolbref impact event scalerevised iesr formsresults mean age total 577 patients 49 17 1987 years ratio female male 352 225 mean age patients pd ha ms ep pnp cvd 65 11 39 12 38 10 47 17 61 12 60 15 years respectively iesr scores found higher younger group comorbid disease contacted covid19 patients diagnosed covid19 group high iesr score rate dit found high iesr scores negatively correlated qol iesr total scores found highest cvd group lowest pd group ratio dit found highest pnp group lowest ep group contact covid19 patients high ep ha groupconclusions results covqolcnd study showed lockdown causes posttraumatic stress deterioration qol cndpmid34344010 doi101159 000517380,0.0
research progress effect rhei radix et rhizoma anthraquinone treatment autoimmune diseases zhongguo zhong yao za zhi 2021 jan 46 1 1523 doi 1019540 jcnkicjcmm20201012601abstractrhei radix et rhizoma first recorded shennong ben cao jing wide range pharmacological activities autoimmune disease kind disease damages tissue structure function immune cells components due impairment immune tolerance function including atherosclerosis multiple sclerosis gout rheumatoid arthritis autoimmune thyroiditis ulcerative colitis type 1 diabetes iga nephropathy recent years clinical experimental studies show rhei radix et rhizoma potential therapeutic effects autoimmune diseases guidance theory traditional chinese medicine paper reviews therapeutic intervening effects rhei radix et rhizoma main active ingredient anthraquinone autoimmune diseases also puts forward new study directions view existing problems studies rhubarb anthraquinone aim provide reference clinical treatment scientific studies effect rhei radix et rhizomaon autoimmune diseasespmid33645046 doi1019540 jcnkicjcmm20201012601,0.0
experimental autoimmune encephalomyelitis methods mol biol 2021 2285375384 doi 101007 9781071613115_27abstractexperimental autoimmune encephalomyelitis originally experimental allergic encephalomyelitis wellknown animal model multiple sclerosis immune mediated demyelinating inflammatory chronic disease central nervous system experimental disease widely utilized test new therapies preclinical studies investigate new hypothesis possible pathogenic mechanisms autoimmune reaction directed central nervous system generally investigate interactions immune system central nervous system lead neuroinflammation experimental autoimmune encephalomyelitis may induced following different protocols mammals including nonhuman primates autoreactive cd4+ tlymphocytes directed myelin antigens main factors introducing model describe protocol induce active eae inbred mice report table different clinical courses eae depending combination antigen mouse strain provide indications evaluate clinics pathology induced diseasepmid33928565 doi101007 9781071613115_27,1.0
estimated connectivity networks outperform observed connectivity networks classifying people multiple sclerosis disability groups neuroimage clin 2021 sep 25 32102827 doi 101016 jnicl2021102827 online ahead printabstractbackground multiple sclerosis ms neurodegenerative neuroinflammatory disease causing lesions disrupt brains anatomical physiological connectivity networks resulting cognitive visual motor disabilities advanced imaging techniques like diffusion functional mri allow measurement brains structural connectivity sc functional connectivity fc networks can enable better understanding disruptions cause disability people ms pwms however advanced mri techniques used mainly research purposes expensive timeconsuming require highlevel expertise acquire process alternative network modification nemo tool can used estimate sc fc using lesion masks derived pwms reference set controls connectivity networksobjective test hypothesis estimated sc fc esc efc nemo tool based individuals lesion masks can used classify pwms disability categories just well sc fc extracted advanced mri directly pwms also aim find connections important differentiating disability vs evidence disability groupsmaterials methods one hundred pwms age455 114 years 66 female disease duration 1297 807 years included study expanded disability status scale edss used assess disability 67 pwms disability edss 2 observed sc fc extracted diffusion functional mri directly pwms respectively nemo tool used estimate remaining structural connectome esc removing streamlines reference set tractograms intersected lesion mask nemo tools esc used input deep neural network estimate corresponding fc efc logistic regression ridge regularization used classify pwms disability categories disability vs evidence disability based demographics clinical information sex age race disease duration clinical phenotype spinal lesion burden either pairwise entries regional summaries one following matrices sc fc esc efc area roc curve auc used assess classification performance univariate statistics parameter coefficients classification models used identify features important differentiating groupsresults regional esc efc models outperformed observed fc sc counterparts pvalue 005 pairwise esc sc performed similarly p 010 regional esc efc models higher auc 066068 pairwise models 060065 regional efc highest classification accuracy across models ridge regression coefficients regional efc regional observed fc models significantly correlated pearsons r 052 pvalue 10e7 decreased estimated sc node strength default mode ventral attention networks increased efc node strength visual networks associated evidence disabilitydiscussion first time use clinically acquired lesion masks estimate structural functional connectomes patient populations better understand brain lesiondysfunction mapping pwms models based nemo tools estimates sc fc better classified pwms disability level sc fc observed directly individual using advanced mri work provides viable alternative performing highcost advanced mri patient populations bringing connectome one step closer clinicpmid34601310 doi101016 jnicl2021102827,0.0
preliminary study hsamir626 change cerebrospinal fluid parkinsons disease neurol india 2021 janfeb 69 1 115118 doi 104103 00283886310102abstractcontext host micrornas reported suppress tumor growth invasion metastasis play roles neurodegeneration disorders moreover microrna changes found peripheral blood cerebrospinal fluid csf brain tissues central nervous system diseases including glioma alzheimers disease ad parkinsons disease pd multiple sclerosis depression compared body fluids csf can reflect brain pathological processes accuratelyaims understand whether microrna expression may misregulated patients pd discover potential diagnostic biomarkers promising therapeutic targets pdmaterials methods realtime reversetranscription polymerase chain reaction rtpcr compared csf microrna 15 pd patients 11 ad patients 16 controls neurologic disorders encephalitis guillainbarre syndromeresults finally identified hsamir626 changes csf pd patients mean expression level hsamir626 significantly reduced csf pd patients compared ad patients controlsconclusions approach provides preliminary research identifying biomarkers csf used detection diagnosis monitoring pdpmid33642281 doi104103 00283886310102,0.0
emotional disorders associated multiple sclerosis handb clin neurol 2021 183197220 doi 101016 b9780128222904000098abstractmultiple sclerosis ms associated high prevalence emotional mood disorders emotional disorders may worsen illness progression affect quality life patients families ms often associated depression increased risk suicide poor adherence treatment decreased functional status quality life diagnosis treatment emotional mood disorders patients often challenging since several symptoms disorders overlap ms prevalent emotional disorders ms include bipolar disorder anxiety disorders emotional blunting apathy pseudobulbar affect early recognition treatment comorbidities contribute reduction disability even decreased mortality aim chapter provide uptodate review mood emotional disorders often associated ms focusing epidemiology clinical features pathogenesis assessment treatment interplay psychosocial impact chronic disability demyelinating structural lesions brain precipitating emotional mood disorders discussed well implications diagnosis treatmentpmid34389118 doi101016 b9780128222904000098,1.0
vaccination multiple sclerosis present stage zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 4448 doi 1017116 jnevro202112107244abstractimmunization patients autoimmune diseases rising lot concerns previously demonstrated vaccination ms patients associated increased risk exacerbations personalized approach needed define immunization schedule decision made based course disease treatment used multiple sclerosis absolute contraindication vaccination authorized vaccine can used ms patientspmid34387445 doi1017116 jnevro202112107244,0.0
plasma creatinine level predict respiratory function amyotrophic lateral sclerosis j neuromuscul dis 2021 feb 23 doi 103233 jnd200583 online ahead printabstractin amyotrophic lateral sclerosis als lower plasma creatinine level associated shorter survival faster functional decline clear creatinine associated respiratory outcome analyzed retrospectively population unselected als patients multipleregression coxregression analyses performed included 233 patients mean age 628 mean disease duration 186 months baseline creatinine significantly associated alsfrsr decline rate predictive value disclosed fvc decline rate survival confirm creatinine marker respiratory outcomepmid33646173 doi103233 jnd200583,0.0
toward allrussian conference international participation quot multiple sclerosis demyelinating diseases 4th congress rokirsquot september 2325 2021 nizhny novgorod zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 104106 doi 1017116 jnevro2021121072104abstracttoward allrussian conference international participation multiple sclerosis demyelinating diseases 4th congress rokirs september 2325 2021 nizhny novgorod pmid34387456 doi1017116 jnevro2021121072104,1.0
relapsingremitting multiple sclerosis clinical immunological aspects pathology example molecules sema4d cd72 zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 7581 doi 1017116 jnevro202112107275abstractobjective study expression sema4d cd100 receptor cd72 role sema4dcd72dependent signal control functions immunocompetent cells relapsingremitting multiple sclerosis rrms material methods studied 76 patients including 52 rrms 41 remission 11 exacerbation 35 women 673 17 men 327 aged 1855 years receive diseasemodifying drugs 24 healthy donors controlled clinical immunological examination patients rrms carried proving involvement sema4d molecule cd72 receptor pathological reactions autoimmune diseaseresults conclusion use semad target treatment rrms scientifically substantiated case positive decision use antisema4d drugs will necessary take account effects semaphorin central nervous system also immune system patients rrmspmid34387451 doi1017116 jnevro202112107275,0.0
antibiotic use risk multiple sclerosis nested casecontrol study emiliaromagna region italy neuroepidemiology 2021 may 718 doi 101159 000515682 online ahead printabstractintroduction known risk factors multiple sclerosis ms include smoking low vitamin d status obesity ebv inflammatory feature disease strongly suggests presence additional infectious agents association use antibiotics ms risk shed light factors still undetermined aimed evaluate association antibiotics ms risk emiliaromagna region rer italymethods adult patients ms seen rer ms center 20152017 eligible 877 patients included clinical information collected matched 5 controls rer residents n 4 205 based age sex place residence index year information antibiotic prescription obtained linkage rer drug prescription databaseresults exposure antibiotic 3 years prior index year associated increased ms risk 152 95 ci 129179 similar results found different classes doseresponse effect founddiscussion conclusions results suggest association use antibiotics ms risk rer population however epidemiological studies done information early life lifestyle factorspmid33965951 doi101159 000515682,0.0
nutraceutical therapeutic potential phycocyanobilin treating alzheimer#39 s disease j biosci 2021 4642abstractalzheimers disease ad devastating neurodegenerative condition provoking loss cognitive memory performances despite huge efforts develop effective ad therapies still cure neurological condition review main biological properties phycocyanobilin pcb accounting potential uses ad pcb given individually released vivo cphycocyanin cpc acts bioactivemoleculemediating antioxidant antiinflammatory immunomodulatory activities pcb cpc able scavenge reactive oxygen nitrogen species counteract lipid peroxidation inhibit enzymes nadph oxidase cox2 animal models multiple sclerosis ischemic stroke compounds induce remyelination demonstrated electron microscopy expression genes mal upregulation lingo1 downregulation treatments also reduce proinflammatory cytokines levels induce immune suppressive genes pcb cpc protects isolated rat brain mitochondria inactivate microglia astrocytes neuronal apoptosis mediators processes involved pathogenic cascade ad thus pcb may effectively mitigate injury condition furthermore pcb can administered safely oral parenteral routes therefore commercially offered nutraceutical supplement pharmaceutical drugpmid34047285,1.0
modern imaging technologies mast cells biology medicine review sovrem tekhnologii med 2021 13 4 93107 doi 1017691 stm202113410 epub 2021 aug 28abstractmast cells play important role body defense allergens pathogens parasites participating inflammation development however evidence contributing pathogenesis number atopic autoimmune well cardiovascular oncologic neurologic diseases allergy asthma eczema rhinitis anaphylaxis mastocytosis multiple sclerosis rheumatoid arthritis inflammatory gastrointestinal pulmonary diseases migraine etc diagnosis many diseases study mast cell functions health disease require identification knowledge adequate imaging techniques mast cells humans different species animals particular importance present review summarizes data major methods mast cell imaging enzyme histochemistry immunohistochemistry well histochemistry using histological stains main histological stains bind heparin acidic mucopolysaccharides contained mast cells stain metachromatically among toluidine blue methylene blue including contained maygrnwaldgiemsa stain thionin pinacyanol others safranin fluorescent dyes berberine avidin also bind heparin longer staining histological dyes alcian blue staining needed label mucosal immature mast cells advanced techniques enzyme histochemistry especially immunohistochemistry enable detect mast cells highselectively using reaction tryptases chymases specific proteases cells immunohistochemical study tryptases chymases speciesspecific differences distribution proteases mast cells humans animals taken account adequate detection immunohistochemical reaction immunoglobulin e receptor fcri ckit receptor specific mast cells although latter important demonstrate proliferation normal malignant growth correct fixation biological material also discussed review great significance histochemical immunohistochemical mast cell detection fluorescent methods immunohistochemistry multimarker analysis combination confocal microscopy reported new technological approaches currently used study various mast cell populationspmid34603768 pmcpmc8482833 doi1017691 stm202113410,0.0
dna methylation epigenetic mechanism development multiple sclerosis acta naturae 2021 aprjun 13 2 4557 doi 1032607 actanaturae11043abstractthe epigenetic mechanisms gene expression regulation group key cellular molecular pathways lead inherited alterations genes activity without changing coding sequence dna methylation c5 position cytosine cpg dinucleotides amongst central epigenetic mechanisms currently number studies devoted identification methylation patterns specific multiple sclerosis ms severe chronic autoimmune disease central nervous system rapid rise however issue contribution dna methylation development different clinical phenotypes highly heterogeneous disease begun attract attention researchers review summarizes data molecular mechanisms underlying dna methylation ms risk factors can affect dna methylation profile thereby modulate expression genes involved diseases pathogenesis focus attention centered analysis published data differential methylation dna various biological samples ms patients obtained using candidate gene approach highthroughput methodspmid34377555 pmcpmc8327151 doi1032607 actanaturae11043,0.0
new therapeutic landscape neuromyelitis optica curr treat options neurol 2021 23 4 13 doi 101007 s11940021006673 epub 2021 mar 30abstractpurpose review review discusses current treatment trends emerging therapeutic landscape patients neuromyelitis optica spectrum disorder nmosd recent findings conventional immune suppressive therapies b cell depletion used longterm treatment however availability recent fdaapproved investigational drugs made therapeutic choices nmosd complexsummary recent randomized clinical trials shown eculizumab inebilizumab satralizumab efficacious therapies aqp4 seropositive nmosd therapies may benefit patients seronegative nmosd including mogassociated disease investigation required population reliable biomarkers guide therapy decisions urgently needed plethora promising investigational therapies currently pipeline exciting novel mechanisms actionpmid33814893 pmcpmc8008025 doi101007 s11940021006673,0.0
multiple sclerosis incidence urinary fecal incontinence almost 9 000 patients followed 10 years germany neuroepidemiology 2021 mar 418 doi 101159 000513234 online ahead printabstractbackground lack large studies urinary ui fecal incontinence fi following multiple sclerosis ms diagnosis thus goal investigate association ms incidence ui fi patients followed 10 years germanymethods study included patients received initial documentation ms diagnosis general practices germany 20052018 index date patients without ms matched 11 ms using propensity scores based sex age index year followup time years general practice charlson comorbidity index score index date randomly selected visit date results retrospective study included 4 461 patients ms 4 461 patients without ms 699 women mean sd age 442 127 years within 10 years index date higher proportion patients ms diagnosed ui 117 vs 32 fi 23 vs 05 p values 0001 without ms ms found associated ui hazard ratio hr 385 fi hr 538 p values 0001 cox regressionsconclusions ui fi frequent complications ms presence complications regularly assessed primary care practicespmid33662954 doi101159 000513234,0.0
innumerable meningiomas arising patient tuberous sclerosis complex decades radiation therapy pediatr dev pathol 2021 apr 710935266211006078 doi 101177 10935266211006078 online ahead printabstractmeningioma common radiationinduced brain neoplasm usually occurring latency 20 35 years multiplicity 10 cases radiationinduced meningiomas rims previously reported patients tuberous sclerosis complex tsc unlike wellknown occurrence familial tumor predisposition syndrome patients report tsc patient developed numerous intracranial meningiomas twenty five year radiation therapy subependymal giant cell astrocytoma sega autopsy examination showed innumerable coalescent benign meningothelial meningiomas grade 1 ranging size 02 cm 33 cm autopsy also showed small residual sega radiationinduced cerebral vasculopathy classic tsc features including several small subependymal nodules candle gutterings white matter radial heterotopia facial angiofibromas dental enamel pitting one ash leaf spot multiple hepatic renal angiomyolipomas nextgeneration sequencing analysis utilizing 500+ gene cancer panel demonstrated chromosomal loss involving majority chromosome 22 including nf2 gene locus well truncating nonsense mutation tsc1 p r509 tsc patients rarely require radiation therapy striking case suggests patients tsc monitored closely cranial therapeutic radiation administeredpmid33826429 doi101177 10935266211006078,0.0
vision attention driving handb clin neurol 2021 178337360 doi 101016 b9780128213773000179abstractsafe driving demands coordination multiple sensory cognitive functions vision attention patients neurologic ophthalmic disease exposed selective pathophysiologic insults drivingcritical systems placing higher risk unsafe driving restricted driving privileges evaluate vision attention contribute unsafe driving across different patient populations ophthalmic disease focus macular degeneration glaucoma diabetic retinopathy cataract neurologic disease focus alzheimers disease parkinsons disease multiple sclerosis unsafe driving generally associated impaired vision attention ophthalmic neurologic patients respectively furthermore patients ophthalmic disease experience degree impairment attention similarly patients neurologic disease experience degree impairment vision numerous studies demonstrated relationship impaired vision unsafe driving neurologic disease remains dearth knowledge regarding relationship impaired attention unsafe driving ophthalmic disease summary chapter confirmsand offers opportunities future research intothe contribution vision attention safe drivingpmid33832685 doi101016 b9780128213773000179,0.0
minimum detectable spinal cord atrophy automatic segmentation investigations using openaccess dataset healthy participants neuroimage clin 2021 oct 4 32102849 doi 101016 jnicl2021102849 online ahead printabstractspinal cord atrophy wellknown biomarker multiple sclerosis ms diseases measured segmenting spinal cord mri image computing average crosssectional area csa slices introduced 25 years ago procedure highly sensitive quality segmentation prone raterbias recently fullyautomated spinal cord segmentation methods remove raterbias enable automated analysis large populations introduced lingering question related automated methods reliable detecting atrophy study evaluated precision accuracy automated atrophy measurements simulating scanrescan experiments spinal cord mri data openaccess spinegeneric project used dataset aggregates 42 sites worldwide consists 260 healthy subjects includes t1w t2w contrasts simulate atrophy volume globally rescaled various scaling factors moreover simulate patient repositioning random rigid transformations applied using deepseg algorithm spinal cord toolbox spinal cord segmented vertebral levels identified average csa c3c5 vertebral levels computed monte carlo sample allowing us derive measures atrophy intra intersubject variability samplesize calculations minimum sample size required detect atrophy 2 unpaired study arms commonly seen ms studies 467 + 139 using t1w 467 + 32 using t2w images minimum sample size detect longitudinal atrophy paired study arms 08 60 + 251 using t1w 10 + 12 using t2w images intrasubject level estimated csa observed study showed good precision compared studies covs across monte carlo transformations 08 t1w 06 t2w images sample sizes seem small like stress results correspond best case scenario dataset used particularly good quality model simulating atrophy encompass variability met reallife datasets simulated atrophy scanrescan variability may oversimplify biological reality proposed framework opensource available https csaatrophyreadthedocsio pmid34624638 doi101016 jnicl2021102849,0.0
content validity integrated yoga module practice remission relapsingremitting multiple sclerosis patients ann neurosci 2021 jan 28 12 2938 doi 101177 09727531211023754 epub 2021 sep 14abstractbackground investigations point beneficial effects yoga alleviating motor cognitive dysfunctions multiple sclerosis ms patients using varying combinations physical breathing meditative practices yoga need validated yoga module holistic approach can used standardized protocol researchers therapistspurpose develop validate integrated yoga module practice relapsingremitting ms patients improve quality lifemethods thorough review literature development yoga module formed expert group 24 experts neurologist used two rounds interactive delphi method combine opinion obtain content validity module online structured questionnaire prepared purpose google form incorporated suggestions obtained experts final module 60 min per session twice day five days per week included warmup exercises customized asanas relaxation techniques om meditation advice yogic diet discussion using yogic concepts stress management also form part holistic approach yoga lifestyle modificationresults analysis divulged 30 39 practices exhibited content validity ratio value greater equal 042conclusion study shown good content validity integrated yoga module future clinical studies planned rule feasibility reliability modulepmid34733052 pmcpmc8558981 doi101177 09727531211023754,0.0
impaired saccadic eye movements multiple sclerosis related altered functional connectivity oculomotor brain network neuroimage clin 2021 oct 4 32102848 doi 101016 jnicl2021102848 online ahead printabstractbackground impaired eye movements multiple sclerosis ms common represent noninvasive accurate measure dys functioning interconnected areas within complex brain network aim study test whether altered saccadic eye movements related changes functional connectivity fc patients msmethods crosssectional eye movement prosaccades antisaccades magnetoencephalography meg data amsterdam ms cohort included 176 ms patients 33 healthy controls fc calculated regions brainnetome atlas six conventional frequency bands cognitive function disability evaluated previously validated measures relationships saccadic parameters fc clinical scores ms patients analysed using multivariate linear regression modelsresults ms pro antisaccades abnormal compared healthy controls relationship saccadic eye movements found fc oculomotor network stronger regional global fc general abnormal eye movements related higher delta theta fc lower beta fc strongest associations found prosaccadic latency fc precuneus beta band 023 p 006 peak velocity fc parietal eye field theta band 025 p 005 gain fc inferior frontal eye field theta band 025 p 003 prosaccadic latency also strongly associated disability scores cognitive dysfunctionconclusions impaired saccadic eye movements related functional connectivity oculomotor network clinical performance ms study also showed addition global network connectivity studying regional changes meg studies yield stronger correlationspmid34624635 doi101016 jnicl2021102848,0.0
increased brain atrophy lesion load associated stronger lower alpha meg power multiple sclerosis patients neuroimage clin 2021 mar 17 30102632 doi 101016 jnicl2021102632 online ahead printabstractin multiple sclerosis interplay neurodegeneration demyelination inflammation leads changes neurophysiological functioning study aims characterize relation reduced brain volumes spectral power multiple sclerosis patients matched healthy subjects restingstate eyes closed collected magnetoencephalographic data 67 multiple sclerosis patients 47 healthy subjects matched age gender additionally quantified different brain volumes magnetic resonance imaging mri first principal component analysis mriderived brain volumes demonstrates atrophy can largely described two components one overall degenerative component correlates strongly different cognitive tests one component mainly captures degeneration cortical grey matter strongly correlates age multimodal correlation analysis indicates increased brain atrophy lesion load accompanied increased spectral power lower alpha 810 hz temporoparietal junction tpj increased lower alpha power tpj associated worse results verbal spatial working memory tests whereas increased lower upper alpha power ratio associated slower information processing speed conclusion multiple sclerosis patients increased brain atrophy lesion thalamic volumes demonstrated increased lower alpha power tpj reduced cognitive abilitiespmid33770549 doi101016 jnicl2021102632,1.0
adherence treatment multiple sclerosis health care program medicina b aires 2021 81 3 311317abstractadherence prescribed treatment chronic diseases occurs multiple sclerosis ms critical factor successful therapeutic response objective study evalua te association demographic variables adherence treatment population ms patients argentina retrospective cohort study ms patients received treatment diseasemodifying drugs included drug dispensing database national care medical program pami programa asistencia mdica integral conducted optimal adherence defined acquisition drug greater 80 9month followup total 648 patients included mean age 55 years iqr 4664 594 women mean adherence treatment 67 iqr 4489 optimal adherence documented 355 cases adherence injectable medications 10 lower oral drugs p 00001 use original brands associated 74 greater adherence generic drugs p 0001 conclusion adherence treatment suboptimal patagonian region use injectables generic drugs associated lower adherence therapy data important order planning sociosanitary programs aim increase therapeutic adherencepmid34137688,0.0
icobrain ms 51 combining unsupervised supervised approaches improving detection multiple sclerosis lesions neuroimage clin 2021 jun 4 31102707 doi 101016 jnicl2021102707 online ahead printabstractmultiple sclerosis ms chronic autoimmune inflammatory neurological disease central nervous system diagnosis nowadays commonly includes performing mri scan sensitive imaging test ms ms plaques commonly identified fluidattenuated inversion recovery flair images hyperintense regions highly varying terms shapes sizes locations routinely classified accordance mcdonald criteria recent years seen increase works aimed development various semiautomatic automatic methods detection segmentation classification ms plaques paper present automatic combined method based two pipelines traditional unsupervised machine learning technique deeplearning attentiongate 3d unet network deeplearning network specifically trained address weaker points traditional approach namely difficulties segmenting infratentorial juxtacortical plaques realworld clinical mris trained validated multicenter multiscanner dataset contains 159 cases t1 weighted t1w flair images well manual delineations ms plaques segmented validated panel raters detection rate quantified using lesionwise dice score simple label fusion implemented combine output segmentations two pipelines combined method improves detection infratentorial juxtacortical lesions 14 31 respectively comparison unsupervised machine learning pipeline used performance assessment baselinepmid34111718 doi101016 jnicl2021102707,0.0
vivo tensorvalued diffusion mri focal demyelination white deep grey matter rodents neuroimage clin 2021 30102675 doi 101016 jnicl2021102675 epub 2021 apr 15abstractbackground multiple sclerosis ms chronic inflammatory demyelinating disease leading damage white matter wm grey matter gm magnetic resonance imaging mri modality choice assess brain damage ms unmet need mri achieving higher sensitivity specificity msrelated microstructural alterations wm gmobjective explore whether tensorvalued diffusion mri dmri can yield sensitive microstructural readouts focal demyelination cerebral wm deep gm dgm methods eight rats underwent llysophosphatidylcholine lpc injections wm striatum introduce focal demyelination multimodal mri performed 7 tesla 7 days tensorvalued dmri complemented diffusion tensor imaging quantitative mri proton magnetic resonance spectroscopy mrs results quantitative mri mrs confirmed lpc injections caused inflammatory demyelinating lesions wm dgm tensorvalued dmri illustrated significant decline microscopic fractional anisotropy fa lpctreated wm dgm p 0005 along marked increase isotropic kurtosis mki dgm p 00001 conclusion tensorvalued dmri bears considerable potential microstructural imaging ms suggesting regional fa decrease may sensitive indicator ms lesions regional mki increase may particularly sensitive detecting dgm lesions mspmid34215146 doi101016 jnicl2021102675,1.0
neuroprotective potential caffeic acid phenethyl ester cape cns disorders mechanistic therapeutic insights curr neuropharmacol 2021 jun 8 doi 102174 1570159x19666210608165509 online ahead printabstractneurological disorders like alzheimers disease ad parkinsons disease pd stroke amyotrophic lateral sclerosis huntingtons disease hd epilepsy traumatic brain injury tbi depression anxiety responsible thousands deaths worldwide every year increase life expectancy rise prevalence disorders age one major risk factors neurological disorders aged population set rise 125 billion 2050 growing concern look new therapeutic molecules treat agerelated diseases caffeic acid phenethyl ester cape molecule obtained number botanical sources bark conifer trees well propolis extracted beehives though cape remains relatively unexplored human trials possesses antioxidant antiinflammatory antimitogenic anticancer activities shown preclinical studies apart also exhibits tremendous potential treatment neurological disorders modulation multiple molecular pathways attenuation behavioural deficits present article reviewed therapeutic potential cape mechanisms treatment neurological disorderspmid34102977 doi102174 1570159x19666210608165509,1.0
thrombin generation potential enhanced systemic sclerosis impact selected endothelial biomarkers clin exp rheumatol 2021 mar 24 online ahead printabstractobjectives systemic sclerosis ssc rare immunemediated heterogenous entity characterised excessive tissue fibrosis vascular injury recently increased risk thromboembolic events documented disease aim investigate prothrombotic plasma properties together selected laboratory biomarkers endothelial injury sscmethods 56 clinically stable ssc patients 67 wellmatched controls assessed plasma thrombin generation profile measured circulating vascular cell adhesion molecule1 vcam1 cellular fibronectin cfn thrombomodulin well analysed relationships disease clinical parameters autoimmune antibodies profileresults ssc characterised 183 increased endogenous thrombin potential etp 145 higher thrombin peak p0001 also adjustment potential confounders similar endothelial damage biomarkers compared controls surprisingly raised thrombin generation related lower thrombomodulin vcam1 inflammatory markers factor viii activity blood eosinophilia predicted positively etp whereas platelet count thrombomodulin negative impact parameter multiple regression model intriguingly patient group also 67 extended lagtime p001 adjustment confounders independently determined higher thrombomodulin cfn well lower vcam1 former cyclophosphamide therapy thus severe type disease referred increased thrombin generationconclusions ssc characterised enhanced thrombin generation potential might contribute higher risk thromboembolic events disease endothelium may play hereby additional role although large observational experimental studies needed verify hypothesispmid33769265,0.0
sleep disorders relapsingremitting multiple sclerosis patients wiad lek 2021 74 2 257262abstractobjective aim study aimed evaluating relationships sleep disorders sd cognitive impairment ci anxiety depression patients relapsingremitting multiple sclerosis rrms patients methods materials methods one hundred five patients rrms 80 females 25 males aged 22 67 years mean age 41 810 7 edss3 51 6 disease duration dd 10 38 5 years enrolled study participants completed questionnaires sleep pittsburgh sleep quality index psqi cognitive functions montreal cognitive assessment moca anxiety hamilton anxiety rating scale hama depression beck depression inventory bdi results results according psqi score patients divided two groups n42 without sd n63 patients sd older 45 361 66 vs 39 411 27 p0005 higher edss score 3 980 26 vs 3 140 19 p0 008 bdi 13 791 14 vs 8 960 86 p0 0009 hama 24 521 42 vs 16 560 99 p0 0001 scales compared patients without sd frequency anxiety p0 0034 depression p0 038 significantly higher rrms patients compared without sd significant difference found gender dd moca score patients sd significant negative correlation moca bdi score r 0 42 p0 005 found group patients without sd significant negative correlation moca edss r 0 27 p0 03 moca bdi r 0 26 p0 043 moca hama r 0 25 p0 041 score detectedconclusion conclusions insomnia type sd rrms patients associated older age higher edss score presence anxiety depressionpmid33813482,0.0
mind diet adherence cognitive performance framingham heart study j alzheimers dis 2021 jun 1 doi 103233 jad201238 online ahead printabstractbackground adherence mediterraneandash neurodegenerative delay mind diet previously associated cognitive decline dementia knowledge prior study investigated association mind diet measures brain volume silent brain infarcts sbis brain atrophyobjective evaluated whether adherence mind diet associated superior cognitive function larger brain volumes fewer sbis less cognitive decline communitybased framingham heart studymethods 2 092 participants meansd age 619 completed food frequency questionnaires averaged across maximum 3time points examination cycles 5 6 7 cognitive testing examination cycle 7 present study baseline 19982001 meansd 6611 years baseline n 1 584 subset participants also completed brain magnetic resonance imaging mri examination cycle 7 n 1 904 addition participants dementia stroke relevant neurological diseases significant head trauma subdural hematoma multiple sclerosis excluded analysesresults higher mind diet scores associated better global cognitive function se +003sd001 p 0004 verbal memory visual memory processing speed verbal comprehension reasoning larger total brain volume tbv following adjustments clinical lifestyle demographic covariates brain mri measures ie hippocampal volume lateral ventricular volume white matter hyperintensity volume sbis cognitive declineconclusion higher mind diet scores associated better cognitive performance larger tbv baseline cognitive decline clinical trials needed ascertain whether adopting mind diet affects trajectories cognitive declinepmid34092629 doi103233 jad201238,0.0
quantifying disease pathology predicting disease progression multiple sclerosis clinical routine t2flair mri neuroimage clin 2021 may 24 31102705 doi 101016 jnicl2021102705 online ahead printabstractbackground although quantitative measures researchquality mri provide means study multiple sclerosis ms pathology vivo metrics often unavailable legacy clinical datasetsobjective determine well automaticallygenerated quantitative snapshot brain pathology measured clinical routine t2flair mri can substitute conventional measures research mri terms capturing multifactorial disease pathology providing similar clinical relevancemethods mri researchquality sequences conventional clinical t2flair acquired 172 ms patients baseline neurologic disability assessed baseline fiveyears later five measures thalamus volume lateral ventricle volume medulla oblongata volume lesion volume network efficiency quantifying disparate aspects neuropathology lowresolution t2flair applied predict standard researchquality mri measures compared regard association future neurologic disability disease progression five yearsresults combination five t2flair measures explained variance standard researchquality mri t2flair measures associated neurologic disability cognitive function fiveyears later r2 0279 p 0001 r2 0382 p 0001 similar standard researchquality mri r2 0279 p 0001 r2 0366 p 0001 also similarly predicted disability progression five years correctlyclassified 698 p 0034 compared standard researchquality mri correctlyclassified 724 p 0022 relapsingremitting msconclusion set five t2flaironly measures can substitute standard researchquality mri especially relapsingremitting ms clinical t2flair available can used obtain substantially quantitative information brain pathology disability currently standard practicepmid34091352 doi101016 jnicl2021102705,0.0
risk factors multiple sclerosis kabardinobalkar republic zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 6569 doi 1017116 jnevro202112107265abstractthe purpose study study features representation risk factors development multiple sclerosis ms kabardinobalkar republic kbr material methods results examination follow patients ms 5 years 20122015 living two regions cbdnalchik prokhladnensky districtwere analyzed diagnosis ms mcdonald criteria 2010 used edss scale used assess severity invalidization registration risk factors development ms carried basis unified questionnaire diagnosis ms established based criteria macdonald 2017 results discussion contact potentially dangerous chemical compounds consumption smoked meat products history viral infections significantly common residents prokhladnensky district differences significant p005 patients ms likely suffered scarlatina n23 195 n14 134 95 ci 043 032101 patients scarlet fever age 15 years n7 63 n1 09 95 ci 245 192321 p0041 also main group patients chickenpox common n70 625 n55 411 95 ci 078 065094 p0032 closest association chickenpox ms development occurred patients main group disease age 7 years p0041 pmid34387449 doi1017116 jnevro202112107265,0.0
devic#39 s opticomyelitis case report authors#39 clinical practice wiad lek 2021 74 2 367370abstractthe aim analyze contemporary scientific literature devics opticomyelitis present case report clinical practice based patients complaints case history features clinical course objective neurological status clinical laboratory additional examination methods characteristic mrpatterns consultations related specialists differential diagnostics made clinical diagnosis according icd10 g360 devics opticomyelitis exacerbation sustained bilateral lesion optic nerves form retrobulbar neuritis development partial atrophy optic nerves eyes spinal cord lesions common cystic cicatrical atrophic alterations c1th8 level moderate lower paraparesis expressed sensory ataxia sensory disturbances descending conductive type th10 impaired function pelvic organs type acute urinary retention asthenic neurotic syndrome widespread cases demyelinating pathology medical practice complexity differential diagnostics determine need specific diagnostic algorithm algorithm consider anamnestic data along course disease clinical laboratory instrumental examination including neuroimaging analysis csf oligoclonal bands analysis igg antibodies aqp4 will allow carry diagnostics decide tactics management patients cohort research needed conduct additional studies optimization tactics dynamics monitoring improvement diagnostic treatment rehabilitation measures patients devics opticomyelitis including appropriate immunological control given complexity differential diagnostics affinity pathology multiple sclerosispmid33813502,0.0
possibilities art therapy color therapy rehabilitation multiple sclerosis zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 4955 doi 1017116 jnevro202112107249abstractthe purpose study study effectiveness nondrug methods prevention rehabilitation patients various variants multiple sclerosis ms outpatient settingsmaterial methods group 35 patients limited mobility various variants course ms continuous art therapy performed art lectures work various art materials markers pastels etc average duration training cycle group 6 months classes held outpatient basis impossible attend classes remotelyresults positive results obtained double psychological testing 68 patients decreased levels depression anxiety hads scale 34 patients refused take antidepressants however positive psychotherapeutic dynamics background art therapy reason cancel main basic treatmentconclusion art therapyart therapy division color therapy diagnosis condition treatment color synthesis medicine art psychology ms patients following color combinations recommended working art materialsstimulating red orange coral yellow soothing green blue blue purple negative colors excluded black gray dirty shades mixture black graypmid34387446 doi1017116 jnevro202112107249,0.0
diffusion basis spectrum imaging measures antiinflammatory neuroprotective effects fingolimod murine optic neuritis neuroimage clin 2021 jun 17 31102732 doi 101016 jnicl2021102732 online ahead printabstractobjective prospectively determine whether diffusion basis spectrum imaging dbsi detects differentiates quantitates coexisting inflammation demyelination axonal injury axon loss mice optic neuritis due experimental autoimmune encephalomyelitis eae determine dbsi accurately measures effects fingolimod underlying pathologymethods eae induced 7weekold c57bl 6 female mice visual acuity va assessed daily detect onset daily oraltreatment either fingolimod 1 mg kg saline given ten weeks vivo dbsi scans optic nerves performed baseline 2 6 10weeks post treatment dbsiderived metrics including restricted isotropic diffusion tensor fraction putatively reflecting cellularity nonrestricted isotropic diffusion tensor fraction putatively reflecting vasogenic edema dbsiderived axonal volume axial diffusivity putatively reflecting axonal integrity increased radial diffusivity putatively reflecting demyelination mice killed immediately last dbsi scan immunohistochemical assessmentresults optic nerves fingolimodtreated mice exhibited significantly better p 005 va salinetreated group time point tenweek treatment dbsiderived nonrestricted restrictedisotropicdiffusiontensor fractions axonal volumes significantly different p 005 baseline values fingolimodtreated mice transient dbsi decrease dbsi increase detected fingolimod treatment dbsiderived metrics assessed vivo significantly correlated p 005 corresponding histological markersconclusion dbsi used assess changes underlying optic nerve pathologies eae mice exhibiting great potential noninvasive outcome measure monitoring disease progression therapeutic efficacy mspmid34166868 doi101016 jnicl2021102732,1.0
role viral infections multiple sclerosis pathogenesis among indian population neurol india 2021 mayjun 69 3 681685 doi 104103 00283886319209abstractbackground role viral infections multiple sclerosis ms pathogenesis unclearobjective certain neurotropic viruses previously linked ms among white population studied including epsteinbarr virus human herpesvirus6 hhv6 msassociated retrovirus msrv material methods sixtytwo ms patients 37 recent clinical relapse 65 controls neurological disorders included blood cerebrospinal fluid csf samples obtained processed primary objective determining whether intrathecal multiplication viruses study ebv hhv6 b human endogenous retrovirus breach bloodbrain barrier associated viral presence peripheral blood csfresults evidence breach bloodbrain barrier seen 865 patients evidenced abnormal csf serum albumin index mri ebv nuclear antigen ebna1 igg seen 89 ms patients 58 controls p 0001 however hhv6 igg similar groups 85 versus 81 p 045 affinity immunoblotting reaction intrathecal igg synthesis ebna1 antigen demonstrable 26 16 62 patients none hhv6 subset patients showed significant elevation mean copy number plasma ebv dna relapse trend among patients harboring hhv6b evidence isolated intrathecal viral presence multiplication seenconclusions results study suggest viruses studied namely ebv hhv6 role triggering relapses peripheral mechanism rather direct role intrathecal multiplicationpmid34169868 doi104103 00283886319209,0.0
sarscov2 covid19 patients degree immunosuppression reumatol clin 2021 augsep 17 7 408419 doi 101016 jreuma202008004 epub 2020 sep 11abstractbackground clear whether patients degree immunosuppression worse outcomes sarscov2 infection compared healthy peopleobjective carry narrative review information available infection sarscov2 immunosuppressed patients especially patients cancer transplanted neurological diseases primary secondary immunodeficienciesresults patients cancer recent cancer treatment chemotherapy surgery sarscov2 infection higher risk worse outcomes transplant patients renal cardiac hepatic neurological pathologies multiple sclerosis ms neuromyelitis optica nmods myasthenia gravis mg primary immunodeficiencies infection human immunodeficiency virus hiv association immunosuppressants studies shown tendency worse outcomesconclusion given little evidence far behaviour sarscov2 infection immunosuppressed patients unclear current studies shown worse outcomes except patients cancerpmid34630575 pmcpmc7486041 doi101016 jreuma202008004,0.0
role peroxisome proliferatoractivated receptor addiction novel drug target curr top med chem 2021 may 21 doi 102174 1568026621666210521165532 online ahead printabstractthe peroxisome proliferator activated receptors ppars superfamily wellrecognized ligandbinding nuclear receptors comprising three isoforms ppar ppar ppar response endogenous lipid messengers ppars trigger transcription genes related wider spectrum physiological phenomena including fatty acid oxidation inflammation adipogenesis among many others thus importance ppars putative protective therapy health issues increased interest studying nuclear receptors including management neurodegenerative disorders multiple sclerosis likely addiction recent years several pieces evidence animal models demonstrated promising role ppars critical element interventions addictive behaviors reducing reinforcing properties addictive substances alcohol however lack data scope far unexplored function ppars additional drugs cannabis opioids methamphetamine cocaine similar scenario found management bingetype eating disorders thus review recent advances understanding relevance ppar controlling addictionpmid34061003 doi102174 1568026621666210521165532,0.0
letter editor sexual support iranian women multiple sclerosis treatment process sufficient insufficient int j ms care 2021 mayjun 23 3 142 doi 107224 153720732020048 epub 2021 jun 17no abstractpmid34177387 pmcpmc8218583 doi107224 153720732020048,0.0
increased intracranial pressure patient neuromyelitis optica spectrum disorder caspian j intern med 2021 12 suppl 2 s435s438 doi 1022088 cjim120435abstractbackground neuromyelitis optica spectrum disorder nmosd autoimmune astrocytopathic disease affecting central nervous system cns csf pressure patients usually normalcase presentation 30yearold woman admitted complaints headache lower limbs paresis lumbar puncture lp magnetic resonance imaging performed patient opening pressure 42 cm h2o first lp according clinical evidences imaging patients positive aquaporin4 antibody diagnosis nmosd establishedconclusion high intracranial pressure headache however rare may first sign onset acute exacerbation phase nmosdpmid34760100 pmcpmc8559654 doi1022088 cjim120435,0.0
using quality improvement refining program materials exercise promotion comprehensive multiple sclerosis care j healthc qual 2021 julaug 01 43 4 249258 doi 101097 jhq0000000000000279abstractintroduction gap evidencebased knowledge exercise benefits translation benefits among persons multiple sclerosis within clinical practice study represents second cycle plandostudyact ramp assess improve three exercise promotion practice models screening process use healthcare providers bridge knowledgetranslation gap within comprehensive multiple sclerosis caremethods using quality improvement design research team created online survey evaluating program materials healthcare providers ie neurologists nurses physical therapists occupational therapists participants provided written comments suggestions improvement regarding roles responsibilities clarity relatability tools within realworld settingresults healthcare providers submitted 13 suggestions improvement responses informed four specific improvements regarding program materials ie patient screening current exercise behavior referrals provider checklists thereby prompting research team adapt test change ideaconclusions article provides step forward line research focused developing systemsbased process integrating exercise promotion part comprehensive multiple sclerosis carepmid34180869 doi101097 jhq0000000000000279,0.0
pregnancy outcome patients neuromyelitis optica spectrum disorder treated rituximab caseseries study caspian j intern med 2021 12 suppl 2 s491s494 doi 1022088 cjim120491abstractbackground neuromyelitis optica spectrum disorder nmosd neuroinflammatory disorder tendency affect spinal cord optic nerves nmosds predilection women reproductive age adopt aggressive course pregnancy appropriate treatment strategies conception pregnancy wellconsideredcase presentation report pregnancy outcome eight pregnancies following rituximab treatment assessed led 50 live births mean birth weight 277750 sd 54592 grams two patients abortions due doctors recommendation one pregnancy led intrauterine fetal death iufd due nuchal cord spontaneous abortions encountered two patients received rituximab pregnancy major malformations serious neonatal infections encounteredconclusion rituximab administered caution nmosd patients want pregnant probable adverse effects drug discussed patientspmid34760113 pmcpmc8559646 doi1022088 cjim120491,0.0
single transcription factorbased differentiation allowing fast efficient oligodendrocyte generation via sox10 overexpression methods mol biol 2021 2352149170 doi 101007 9781071616017_11abstractoligodendrocytes main glial cell type central nervous system supporting axonal part neurons via myelin lactate delivery conductive myelin formation energy support via lactate can affected diseases multiple sclerosis amyotrophic lateral sclerosis respectively therefore human disease modeling needed gain mechanistic insights drive drug discovery research patientderived induced pluripotent stem cells ipscs serve necessary tool providing infinite cell source patientspecific disease modeling allows investigation oligodendrocyte involvement human diseasesmall moleculebased differentiation protocols generate oligodendrocytes pluripotent stem cells can last 90 days provide transcription factorbased fast efficient protocol generating o4+ oligodendrocytes just 2024 days neural induction phase 812 days sox10 overexpressed either use lentiviral vectors via engineered ipscs inducibly overexpress sox10 doxycycline addition using last method pure o4+ cell population achieved keeping sox10overexpressing neural stem cells culture additional 10 days furthermore o4+ cells can cocultured ipscderived cortical neurons 384well format allowing promyelinating drug screens conclusion provide fast efficient oligodendrocyte differentiation protocol allowing vitro human disease modeling highthroughput coculture system drug discoverypmid34324186 doi101007 9781071616017_11,1.0
modeling complex disease multiple sclerosisupdate 2020 adv immunol 2021 1492534 doi 101016 bsai202103002 epub 2021 mar 29abstractmultiple sclerosis ms complex inflammatory disease central nervous system cns unknown etiology thereby ms uniform disease rather represents spectrum disorders aspect needs modeled specific requirementsfor systematic overview see previous issue review kurschus wortge waisman 2011 however broad consensus critical involvement immune system disease pathogenesis better understand immune system contributes cns autoimmunity model experimental autoimmune encephalomyelitis eae developed eae can induced susceptible animals many different ways popular protocol involving activation selfreactive t cells peptide based myelin oligodendrocyte glycoprotein sequence last 10 years model led major advances understanding immune system especially nature il17producing t cells th17 cells hostmicrobiome interactions gutbrain axis immune system can cause damage different regions brain spinal cord update summarizes main achievements field last 10 yearspmid33993919 doi101016 bsai202103002,1.0
factors associated olfactory dysfunction patients multiple sclerosis basic clin neurosci 2021 janfeb 12 1 8994 doi 1032598 bcn12113681 epub 2021 jan 1abstractintroduction impaired sense smell remarkable impact quality life seen variety neurodegenerative diseases parkinson disease study assessed olfactory function patients multiple sclerosis ms sniff magnitude test smt methods crosssectional study conducted 48 patients ms questionnaire including demographic clinical variables completed patient smt used evaluation olfactory functionresults olfactory dysfunction found 146 patients 83 hyposmia 63 anosmia older age longer disease duration higher hospital admission rate lower minimental status examination score secondary progressive course ms significantly related olfactory dysfunctionconclusion secondary progressive ms markers advanced disease toward neurodegenerative phase including older age longer disease duration lower cognitive function can associated olfactory dysfunction ms patientspmid33995931 pmcpmc8114867 doi1032598 bcn12113681,0.0
structural basis cd97 recognition decayaccelerating factor cd55 suggests mechanosensitive activation adhesion gpcrs j biol chem 2021 may 13100776 doi 101016 jjbc2021100776 online ahead printabstractthe adhesion g proteincoupled receptor cd97 ligand complement decayaccelerating factor cd55 important binding partners human immune system dysfunction binding linked immune disorders multiple sclerosis rheumatoid arthritis well various cancers previous literatures indicated cd97 includes three five egf domains nterminus egf domains can bind nterminal scr domains cd55 however details interaction remain elusive especially cd55 binds highest affinity shortest isoform cd97 egf1 2 5 herein designed chimeric expression construct egf1 2 5 domains cd97 scr14 domains cd55 connected flexible linker determined complex structure crystallography data reveal two proteins adopt overall antiparallel binding mode involving scr13 domains cd55 three egf domains cd97 mutagenesis data confirmed importance egf5 interaction explained binding specificity cd55 cd97 architecture cd55cd97 binding mode together kinetics suggest forceresisting shearing stretch geometry forces applied ctermini proteins circulating environment potential cd55cd97 complex withstand tensile force may provide basis mechanosensing mechanism activation adhesion g proteincoupled receptorspmid33992645 doi101016 jjbc2021100776,0.0
coexistence depression low bone mineral density vitamin d deficiency patients multiple sclerosis psychiatr danub 2021 summer 33 2 201no abstractpmid34185750,0.0
neurologic manifestations covid19 adv exp med biol 2021 1318343353 doi 101007 9783030637613_20abstractneurological manifestations novel coronavirus disease covid19 reported occur much 37 affected patients manifestations range headache dizziness altered mental status consciousness anosmia ageusia sensory disturbances stroke mechanisms neurological symptoms arise yet determined may either proceed indirect consequence systemic hyperinflammation result direct invasion virus neural glial cells neural invasion can explain retrograde pathway encephalitis early manifestation anosmia invading olfactory bulb moreover case attacking brain stem may take part early apnea manifestation reported patients additionally neurotropism virus cause acute hemorrhagic encephalitis hyperinflammation can acute prolonged effects nervous system acute demyelination predisposition multiple sclerosis moreover proinflammatory state contributes hypercoagulation turn result cerebrovascular injuries covid19 patients chapter discuss neurologic manifestations covid19 looked multifactorial entangled phenomenonpmid33973188 doi101007 9783030637613_20,1.0
highlighting gaps spinal cord injury research activitybased interventions upper extremity scoping review neurorehabilitation 2021 may 6 doi 103233 nre210042 online ahead printabstractbackground upper extremity activitybased therapy neurologic disorders employs highintensity high repetition functional training exploit neuroplasticity improve function research focused highintensity upper extremity activitybased therapy persons spinal cord injury sci limitedobjective summarize highintensity activitybased interventions used neurological disorders current potential application scimethods scoping review included articles medline cinahl cochrane central otseeker criteria noninvasive activitybased interventions delivered atleast three times week two weeks upper extremity functional outcomes 13 years older english language neurological disorders three months post onset injuryresults search yielded 172 studies seven studies sci adults activitybased interventions sci included taskspecific training gaming without electrical stimulation robotic exoskeleton populations found review included studies stroke cerebral palsy multiple sclerosis thirtyfour different interventions reported populations comparison extensive stroke research work sci found highintensity interventions using virtual reality brain stimulation rehabilitation devices applications home telerehab settingsconclusion results highlight critical gaps within upper extremity highintensity activitybased research scipmid33967071 doi103233 nre210042,0.0
comparison efficacy vestibular rehabilitation noisy galvanic vestibular stimulation improve dizziness balance patients multiple sclerosis j vestib res 2021 may 1 doi 103233 ves201609 online ahead printabstractbackground dizziness imbalance common symptoms patients multiple sclerosis pwms rehabilitation interventions varying greatly effectivenessobjective compare effectiveness vestibular rehabilitation therapy vrt noisy galvanic vestibular stimulation ngvs dizziness balance pwmsmethods singleblind randomized controlled trial twentyfour pwms randomly divided groups vrt ngvs control vrt ngvs groups underwent intervention program patients assessed composite score anteroposterior lateral directions cs ap lat obtained sensory organization test sot dizziness handicap inventory dhi activitiesspecific balance confidence scale abc results vrt group showed greater improvements cs ap lat dhi total score abc total score compared ngvs group control group significant difference found ngvs group control group results approximately stable 4week followupconclusions findings provided evidence effectiveness vrt improvement dizziness balance pwms improvements associated ngvs studies needed assess effectiveness ngvs dizziness balance pwmspmid33967075 doi103233 ves201609,0.0
modeling costeffectiveness prolongedrelease fampridine treatment walking impairment patients multiple sclerosis sweden j med econ 2021 may 81 doi 101080 1369699820211927746 online ahead printabstractaims evaluate costeffectiveness adding prolongedrelease pr fampridine best supportive care bsc versus bsc alone improvement walking ability patients msmethods costutility analysis based markov model developed model responders timed 25foot walk t25fw scores accumulated costs qualityadjusted lifeyears qaly adults ms expanded disability status scale edss scores 4 7 analysis conducted swedish societal perspectiveresults basecase analysis prfampridine plus bsc led higher qaly gain bsc alone largest direct cost professional care provision followed hospital inpatient stays indirect cost loss earnings due days work incremental costeffectiveness ratio icer prfampridine plus bsc compared bsc alone 57 109 kr qaly 5 607 qaly 1 kr 00981762 8 april 2021 1 6 675 qaly 1 kr 0116890 8 april 2021 1 sensitivity analyses performed resulted icers 500 000 swedish kronor kr 49 088 58 445 1 limitations resource use data specific swedish marketconclusions prfampridine represents costeffective treatment msrelated walking impairment sweden due improvements patients quality life reduced healthcare resource utilizationpmid33966549 doi101080 1369699820211927746,0.0
peculiarities presentation encephalitogenic mbp peptide hladr complexes providing protection predisposition multiple sclerosis acta naturae 2021 janmar 13 1 127133 doi 1032607 actanaturae11008abstractpredisposition multiple sclerosis ms chronic autoimmune disease central nervous system due various factors genetic component considered one important factors hla class ii genes contribute development ms hladrb115 allele group considered one main genetic risk factors predisposing ms group hladrb101 alleles shown protective effect disease russian population work compared binding encephalitogenic fragment myelin basic protein mbp two hladr complexes provide protection predisposition ms hladr1 hladrb10101 hladr15 hladrb11501 respectively found myelin peptide mbp88100 binds hladr1 rate almost order magnitude lower viral peptide hemagglutinin ha true binding mbp8597 hladr15 comparison viral pp65 structure cterminal part peptide plays key role binding hladr1 equally highaffinity nterminal regions peptides ic50 myelin peptide mbp88100 competing viral ha binding hladr1 almost order magnitude higher ha ha also true binding mbp8597 hladr15 comparison viral pp65 thus autoantigenic mbp compete viral peptide binding protective hladr1 however competitive viral peptide hladr15pmid33959392 pmcpmc8084299 doi1032607 actanaturae11008,1.0
review covid19 risk multiple sclerosis j cell immunol 2021 3 2 6877 doi 1033696 immunology3080abstractthe ongoing pandemic novel coronavirus 2019 covid19 resulted 1 million deaths primarily affecting older patients chronic ailments multiple sclerosis ms patients deemed particularly vulnerable given high rates disability increased susceptibility infections also concerns regarding diseasemodifying therapy dmt pandemic many dmts may increase risk infection due immunosuppressive properties furthermore due msrelated chronic inflammatory damage within central nervous system concerns worsening neurological injury covid19 resulted alarmingly high level anxiety stress among ms community leading lack compliance medications routine checkups even failure obtain treatment relapse however currently substantial evidence ms dmt usage associated increased covid19 severity ms patients suffer worse outcomes likely older suffer significant disabilities comorbid conditions also expected general population likewise little evidence demonstrating increased susceptibility ms patients covid19related neurological complications therefore aim summarize recent findings related covid19 ms demonstrating ms dmts appear risk factors severe covid19pmid33959727 pmcpmc8098748 doi1033696 immunology3080,0.0
variables associated selfreported language impairment multiple sclerosis regression analysis int j ms care 2021 marapr 23 2 8592 doi 107224 153720732020096 epub 2021 apr 14abstractbackground persons multiple sclerosis ms can experience languagerelated symptoms difficulty word finding understanding verbal information structuring discourse symptoms negative psychological interpersonal consequences studies exploring characteristics language impairment ms limited aim study investigate symptomrelated eg fatigue demographic eg age clinical eg ms type social network quality life qol variables associated language impairment msmethods participants recruited internationally complete online questionnaire forward stepwise regression analysis run dependent variable language impairment index communication language assessment questionnaire persons multiple sclerosis clams nineteen independent variables entered regressionresults two hundred two participants completed questionnaire clams language impairment score significantly associated selfreported cognitive impairment speech voice impairment yes response binary question presence language impairment group membership participation qol adjusted r2 value 0717 p 001 conclusions selfreported language impairment ms significantly associated several symptomrelated social network qol variables results provide early model language impairment ms guide future studies treatment approaches causative relationships variablespmid33880085 pmcpmc8047682 doi107224 153720732020096,0.0
ocrelizumabinduced inflammatory bowel diseaselike illness characterized esophagitis colitis ann gastroenterol 2021 34 3 447448 doi 1020524 aog20210582 epub 2021 jan 27abstractocrelizumab intravenous anticd20 monoclonal antibody approved use primary progressive multiple sclerosis due selective depletion blymphocytes herein describe case 56yearold female developed odynophagia bloody diarrhea following treatment ocrelizumab characterized endoscopically ulcerations esophagus colon patient treated highdose intravenous glucocorticoids good clinical responsepmid33948072 pmcpmc8079880 doi1020524 aog20210582,0.0
novel insights multiple sclerosis demyelinating disorders apoptosis autophagy foxo mtor curr neurovasc res 2021 may 5 doi 102174 1567202618999210505124235 online ahead printno abstractpmid33964865 doi102174 1567202618999210505124235,1.0
s1pr1 signaling cancer current perspective adv protein chem struct biol 2021 125259274 doi 101016 bsapcsb202012006 epub 2021 apr 10abstractsphingosine1phosphate receptor 1 s1pr1 gprotein coupled receptor bioactive lysosphingolipid sphingosine 1phosphate s1p s1pr1 belongs sphingosine1phosphate receptor subfamily comprising five members s1pr15 prominent roles regulating endothelial cell cytoskeletal structure cell migration immunomodulation vasculogenesis embryogenesis t cell egress multiple sclerosis review addressing role s1pr1 tumorigenesis therapeutic opportunities target s1pr1 cancerpmid33931142 doi101016 bsapcsb202012006,0.0
astrocytes pathogenesis multiple sclerosis nihon yakurigaku zasshi 2021 156 4 230234 doi 101254 fpj21030abstractmultiple sclerosis ms inflammatory demyelinating disease central nervous system cns designated intractable disease japan characterized dissemination plaquelike sclerosis space time accompanied various symptoms corresponding cns lesion site typically neurological symptoms chronically progress accompanied relapses remissions still curative therapy number studies using ms specimen animal ms model experimental autoimmune encephalomyelitis eae shown ms autoimmune disease targets myelin sheath cns autoreactive t cells b cells play central role pathogenesis ms ms comprise relapsingremitting ms progressive ms latter accumulates clinical disability without relapse based importance adaptive immunity various diseasemodifying drugs developed treat relapsingremitting ms hand effective treatment progressive ms yet established increasing evidence recognized glial cells key components ms immunopathology addition innate immunity adaptive immunity however molecular mechanisms crosstalk immune cells glial cells neurons remain elucidated review ms pathology recent advances diseasemodifying therapy efficiently reduce disease activity relapsingremitting ms introduce update recent evidence astrocyte involved ms pathology including research analyzed mouse eae modelpmid34193702 doi101254 fpj21030,1.0
role double inversion recovery sequence neuroimaging 3 tesla mri neurol india 2021 marapr 69 2 394396 doi 104103 00283886314551abstractdouble inversion recovery dir robust sequence designed suppress fat water signals using two 180 inversion pulses produce prominent gray matter contrast high spatial resolution proven sensitive delineating white matter signal abnormalities conventional mr techniques study highest image contrast lesion load observed using dir flair t2 weighted imaging dir evidently valuable detection demyelinating lesions observed multiple sclerosis ms malignancies epileptogenic foci cortical anomalies hence pictorial review intended assess diagnostic efficacy dir modality clinical neuroimagingpmid33904461 doi104103 00283886314551,1.0
chronic neurological disorders genetic epigenetic markers monitoring pharmacotherapy neurol india 2021 marapr 69 2 252259 doi 104103 00283886314522abstractintroduction chronic neurological diseases major cause mortality morbidity world increasing life expectancy developing world incidence prevalence diseases predicted rise even also contributed increase disabilityadjusted life years dalys noncommunicable diseases treatment diseases also poses challenge multiple genetic epigenetic factors leading varied outcome personalization treatment one way treatment outcome prognosis disease can improved pharmacogenomics plays significant role contextmethodology article reviewed evidence pertaining association genetic epigenetic markers major neurological disorders like multiple sclerosis ms alzheimers disease ad parkinsons disease pd major source burden among neurological disorders types studies included peerreviewed original research articles pubmed database 19992018 results study compiled data regarding specific genetic epigenetic markers significant correlation clinical diagnosis disease prognosis therapy 65 studies single platform review highlights clues vital questions interferon beta ifn therapy fails improve symptoms ms patients cholinesterase inhibitors fail improve cognitive impairment subset people suffering ad individuals levodopa ldopa pd suffer sideeffects ranging dyskinesia hallucination others notconclusion article summarizes genetic epigenetic factors may either require monitoring help deciding future pharmacotherapy patient suffering ms ad pd health care system develops reaches newer heights expect biomarkers used pharmacotherapeutic outcome indicatorspmid33904433 doi104103 00283886314522,0.0
magnetic resonance imaging spinal cord lesions patients multiple sclerosis saskatchewan canada int j ms care 2021 marapr 23 2 4752 doi 107224 153720732019081 epub 2020 apr 14abstractbackground spinal cord lesions scls contribute disability multiple sclerosis ms data saskatchewan canada concerning scls association disability levels patients ms lacking study objectives identify clinicodemographic profiles patients ms respect spinal cord magnetic resonance imaging mri involvement determine frequency individuals mri scls explore differences patients ms without scls respect disability diseasemodifying therapy statusmethods monocentric crosssectional retrospective review prospectively collected data 532 researchconsented patients seen saskatoon ms clinic performed data collected database electronic medical recordsresults 356 patients 669 scl 180 506 cervical cord lesions median expanded disability status scale edss ambulation pyramidal scores patients scls higher patients without scls patients edss scores least 6 scls younger without scls p 01 patients scls 55 less likely continuous diseasemodifying therapy since diagnosis patients without scls adjusted odds ratio 045 95 ci 025081 p 008 conclusions prevalence association disability scls patients ms comparable existing literature patients ms scls higher levels disability attain edss scores least 6 younger agepmid33880079 pmcpmc8047683 doi107224 153720732019081,0.0
vitamin d levels visual system measurements progressive multiple sclerosis crosssectional study int j ms care 2021 marapr 23 2 5358 doi 107224 153720732020005 epub 2020 apr 28abstractbackground vitamin d deficiency associated increased disease activity multiple sclerosis ms role progressive ms elucidated objective determine correlation vitamin d levels visual parameters primary progressive ms ppms secondary progressive ms spms methods serum 25hydroxyvitamin d 25 oh d 25hydroxyvitamin d3 25 oh d3 levels obtained secondary primary progressive ibudilast neuronext trial ms sprintms visual function measurements vitamin d associations determined using pearson correlation generalized linear mixed modelresults analysis included 258 patients mean sd age 556 73 years 527 female 523 ppms mean vitamin d values sufficiency similar ppms spms p 47 p 31 association 25 oh d3 levels visual markers including peripapillary retinal nerve fiber layer thickness spearman r 008 macular volume r 003 ganglion cellinner plexiform layer r 007 25 lowcontrast visual acuity test r 010 statistically significant associations vitamin d levels visual system measurements detected ppms spms subgroupsconclusions vitamin d levels associated optical coherence tomography findings lowcontrast letter acuity group patients progressive mspmid33880080 pmcpmc8047686 doi107224 153720732020005,0.0
experiences african american women multiple sclerosis int j ms care 2021 marapr 23 2 5965 doi 107224 153720732019068 epub 2020 apr 16abstractbackground despite growing understanding african american patients may aggressive course multiple sclerosis ms experience disparities diagnosis treatment fewer studies examined african americans experience ms effect lives study explored experiences african american women ms inform future research practicemethods facetoface semistructured interviews conducted 19 african american women inductive content analysis used identify major categories subcategoriesresults analyses yielded three major categories one believe ms tough living ms keep going many women reported ms diagnosis surprise doctors common belief ms caucasian disease reason many women felt diagnosis delayed physicians initially focused diseases considered typical african american individuals living losses related social family activities independence employment especially challenging faith god coming grips diagnosis health promotion behaviors key strategies dealing ms women also spoke pushing forward working ms challenges taking care thus preserving identity strong black women culturally important construct african american communityconclusions future research explore interactions culture coping strategies development useful valued resources supports african american people mspmid33880081 pmcpmc8047687 doi107224 153720732019068,0.0
effect group counseling plus tailored exercise mobility function multiple sclerosis int j ms care 2021 marapr 23 2 6672 doi 107224 153720732019066 epub 2020 mar 2abstractbackground multiple sclerosis ms impairs muscular function limits individuals ability perform everyday activities requiring mobility people ms frequently exhibit mobility problems ie slower walking speed shorter strides general exercise training eg resistance aerobic provides modest physiological walking mobility benefits however researchers suggest tailoring interventions address mobility specifically conducted phase 2a prepost intervention development study obesityrelated behavioral intervention trials orbit intervention development model mobility exercise plus cognitive behavioral counseling improve function social cognitions known encourage exercisemethods intervention conducted twice per week 8 weeks followed 1 month selfmanaged mobility exercise participants n 29 mean sd age 5224 1136 years mean time since ms diagnosis 11 years assessed baseline followup mobility function social cognitions intervention fidelity indicatorsresults results indicated significant improvements variety valid measures mobility function eg 400m walk selfregulatory efficacy mobility exercise symptom control fidelity measures small medium effect sizesconclusions positive findings suggest intervention seems merit testing randomized pilot study following orbit modelpmid33880082 pmcpmc8047688 doi107224 153720732019066,0.0
impact switching fingolimod versus injectable diseasemodifying therapy cycling risk multiple sclerosisrelated relapses retrospective analysis int j ms care 2021 marapr 23 2 7378 doi 107224 153720732019050 epub 2020 apr 28abstractbackground clinical realworld studies shown significant reductions multiple sclerosis ms relapses fingolimod versus injectable diseasemodifying therapies dmts multiple sclerosis relapse rate incidence compared patients switching injectable dmt fingolimod cycling one injectable dmt another remaining original injectable dmtmethods retrospective analysis performed using commercial medicare supplemental claims data july 1 2010 june 30 2016 adults ms receiving 1 injectable dmt relapses identified msrelated hospitalization outpatient emergency department office visit corticosteroid administration annualized relapse rate ratio estimatedresults 16 352 patients 1110 switchers fingolimod 908 injectable dmt cyclers 14 334 nonswitchers baseline rate incidence ms relapses higher switchers injectable dmt cyclers versus nonswitchers p 001 mean sd relapse rates declined 04 07 04 07 02 05 baseline 02 05 03 06 01 04 followup switchers injectable dmt cyclers nonswitchers respectively relapse incidence declined cohort highest reductions relapse rate incidence switchers fingolimod relapse risk significantly reduced versus injectable dmt cyclers 22 p 0433 nonswitchers 47 p 001 conclusions study provides evidence patients switching injectable dmt fingolimod highest reductions annualized rate incidence ms relapses significantly reduced risk relapse versus injectable dmt cyclers nonswitcherspmid33880083 pmcpmc8047685 doi107224 153720732019050,0.0
upper limb dexterity patients multiple sclerosis important underrated morbidity int j ms care 2021 marapr 23 2 7984 doi 107224 153720732019083 epub 2020 may 15abstractbackground scales assess disability multiple sclerosis ms rarely provide reliable data actual global impairment upper limb dysfunction usually overlooked negative effect patient wellbeing sought analyze associations among upper limb dexterity lower limb speed expanded disability status scale edss score difference upper limb dexterity patients edss scores less 5 5 greater associations upper limb dexterity lower limb speed edss score healthrelated quality life measurements depressionmethods total 140 adults ms evaluated using ninehole peg test timed 25foot walk test edss multiple sclerosis international quality life musiqol questionnaire beck depression inventory thorough descriptiveanalytical research conducted using spearman correlation multiple linear regression structural equation modelingresults upper limb dexterity closely related edss score lower limb speed r 043 vs 029 r 2 038 greatest patients edss scores less 5 p 01 moreover upper limb dexterity negatively associated edss score musiqol questionnaire rs 0557 0321 p 05 correlation depression upper limb dexterity loss higher one lower limb speed 0098 vs 0066 t 196 conclusions upper limb dexterity associated global disability depression healthrelated quality life advocate assessment upper limb dexterity patients ms adopt better approach functional impairmentpmid33880084 pmcpmc8047681 doi107224 153720732019083,0.0
clinical course outcome sarscov2 infection multiple sclerosis patients treated diseasemodifying therapies polish experience neurol neurochir pol 2021 apr 15 doi 105603 pjnnsa20210031 online ahead printabstractintroduction aim study report course outcome sarscov2 infection multiple sclerosis ms patients treated diseasemodifying therapies dmts poland major concern neurologists worldwide course outcome sarscov2 infection patients ms treated different dmts although initial studies suggest unfavourable course infection group patients data limitedmaterials methods study included 396 ms patients treated dmts confirmed sarscov2 infection 28 polish ms centres information concerning patient demographics comorbidities clinical course ms current dmt use well symptoms sarscov2 infection need pharmacotherapy oxygen therapy hospitalisation shortterm outcomes collected 30 january 2021 additional data covid19 cases general population poland obtained official reports polish ministry healthresults 114 males 288 282 females 712 median age 39 years iqr 13 great majority patients ms exhibited relapsingremitting course 372 patients 939 median edss 2 sd 138 mean disease duration 895 iqr 8 years ms patients treated dimethyl fumarate 164 4141 dmts less frequently used interferon beta 82 2070 glatiramer acetate 42 1060 natalizumab 35 884 teriflunomide 25 631 ocrelizumab 20 505 fingolimod 16 404 cladribine 5 126 mitoxantrone 3 076 ozanimod 3 076 alemtuzumab 1 025 overall hospitalisation rate due covid19 cohort 681 27 patients one patient 03 died due sarscov2 infection three 076 patients treated mechanical ventilation 106 268 patients least one comorbid condition significant differences severity sarscov2 infection regarding patient age duration disease degree disability edss lymphocyte count type dmt usedconclusions clinical implications ms patients included study favourable course sarscov2 infection hospitalisation rate mortality rate higher ms cohort compared general polish population continued multicentre data collection needed increase understanding sarscov2 infection impact course ms patients treated dmtspmid33856686 doi105603 pjnnsa20210031,0.0
bullous pemphigoid mimicking cellulitis j investig med high impact case rep 2021 jandec 923247096211008585 doi 101177 23247096211008585abstractbullous pemphigoid bp prevalent autoimmune blistering skin disease western world affecting mainly elderly population diagnosis based clinical assessment along specific immunopathologic findings skin biopsy risk factors include genetic factors environmental exposures several infections including hepatitis b hepatitis c helicobacter pylori toxoplasma gondi cytomegalovirus variety drugs associated bp including limited dipeptidyl peptidase4 inhibitors loop diuretics spironolactone neuroleptics associated neurologic disorders dementia parkinsons disease bipolar disorder previous stroke history multiple sclerosis also described common clinical presentation consists extremely pruritic inflammatory plaques resemble eczematous dermatitis urticaria followed formation tense bullae subsequent erosions typical distribution involves trunk extremities mucosa typically spared affecting 10 30 patients several unusual clinical presentations bp described nonbullous forms erythematous excoriated papules plaques nodules reported findings include urticarial lesions prurigolike nodules multiple small vesicles resembling dermatitis herpetiformis pompholyx vegetating purulent lesions localized intertriginous areas even exfoliative erythroderma recognition management cases can present diagnostic challenge clinicians article describe another variant knowledge first case present cellulitislike presentation patient known history bppmid33847152 doi101177 23247096211008585,0.0
olfactory dysfunction cognition radiologically isolated syndrome relapsingremitting multiple sclerosis eur neurol 2021 apr 818 doi 101159 000514433 online ahead printabstractbackground multiple sclerosis ms neuroinflammatory neurodegenerative demyelinating disease causes cognitive olfactory neurological dysfunctions radiologically isolated syndrome ris radiological findings monitored accepted preclinical stage demyelinating disease considered important period disease pathology therefore study aimed evaluate olfactory cognitive functions clinical correlation ris relapsingremitting ms rrms patients healthy control groupmethods study included 10 rrms patients 10 ris patients 10 healthy controls conducted olfactor evaluation via sniffin sticks test subjects underwent neuropsychometric test battery evaluate cognitive functions including memory visuospatial executive functions depression evaluated using beck depression scale fatigue daily life activity evaluated using fatigue severity scale fss 36item short form survey sf36 respectively disability assessment done expanded disability status scale edss results rrms ris patients olfactory test scores significantly different control group p 005 significant difference odor threshold scores patients rrms ris groups significant correlation memoryoriented cognitive tests olfactory tests rrms ris groupsconclusion olfactory dysfunction can seen ris patients like rrms patients cognitive olfactory dysfunction may together sign degeneration demyelinating diseasespmid33831865 doi101159 000514433,1.0
quantitative susceptibility mapping thalamus basal ganglia systemic lupus erythematosus patients neuropsychiatric complaints neuroimage clin 2021 mar 22 30102637 doi 101016 jnicl2021102637 online ahead printabstractsystemic lupus erythematosus sle autoimmune disease characterized multiorgan involvement although uncommon central nervous system involvement sle termed neuropsychiatric sle npsle exception current knowledge underlying pathogenic mechanisms incomplete however neuroinflammation thought play critical role evidence neurodegenerative diseases multiple sclerosis suggests neuroinflammation correlated brain iron accumulation making quantitative susceptibility mapping qsm potential hallmark neuroinflammation vivo study assessed susceptibility values thalamus basal ganglia np sle patients investigated vivo findings histological analyses postmortem brain tissue derived sle patients used 3t mri scanner acquire singleecho t2weighted images 44 sle patients 20 agematched healthy controls 44 patients sle neuropsychiatric complaints 29 classified nonnpsle 15 npsle seven inflammatory npsle eight ischemic npsle mean susceptibility values thalamus caudate nucleus putamen globus pallidus calculated formalinfixed paraffinembedded postmortem brain tissue including putamen globus pallidus three additional sle patients obtained stained iron microglia astrocytes susceptibility values sle patients agematched controls showed iron levels thalamus basal ganglia changed due disease subgroup sle showed higher susceptibility values correlation found disease activity damage due sle histological examination postmortem brain showed increased iron accumulation results suggest neuroinflammation npsle necessarily go hand hand iron accumulation inflammatory pathomechanism sle may differ one observed neurodegenerative diseases multiple sclerosispmid33812303 doi101016 jnicl2021102637,0.0
investigation il2 ifngamma ebv peptides stimulated whole blood among multiple sclerosis patients healthy individuals intervirology 2021 jun 2516 doi 101159 000517002 online ahead printabstractintroduction epsteinbarr virus ebv doublestranded dna virus 2 phases lytic latent infection host cells infecting b lymphocytes ebv becomes persistent cells healthy individuals t lymphocytes play key role killing ebvinfected b cells statistical studies shown symptomatic ebv infection increases risk msmethods study intended measure immune systems response different components ebv focusing particularly t lymphocytes reaction consequently mrna level il2 ifn liable impressing autoimmune diseases indicators tcell function compared ebna1 brlf1treated whole blood wb cultures 10 healthy individuals 10 ms patients using realtime rtpcrresults analysis results demonstrated significant increased level il2 ms patients healthy subjects exposure peptides also mrna level ifn increased ms patients ebna1treated wb cultureconclusion according studys results ebv peptides can reactivate immune cells especially t lymphocytes may indirectly induce inflammation develop ms however seems longtime exposure peptides reducing effect tcell function faces control infected b lymphocytes difficultiespmid34175848 doi101159 000517002,0.0
validation algorithm detect multiple sclerosis cases administrative health databases piedmont italy application estimate prevalence age urbanization level neuroepidemiology 2021 mar 1017 doi 101159 000513763 online ahead printabstractintroduction italy considered highrisk country multiple sclerosis ms exploiting electronic health archives ehas highly useful continuously monitoring prevalence disease well care delivered patients outcomes aim study validate ehabased algorithm identify ms patients suitable epidemiological purposes estimate ms prevalence piedmont north italy methods ms cases identified period january 1 2012 december 31 2017 linking data 4 different sources hospital discharges drug prescriptions exemptions copayment health care longterm care facilities sensitivity algorithm tested record linkage cohort 656 neurologistconfirmed ms cases specificity tested cohort 2 966 293 residents presumably affected ms undercount estimated capturerecapture method calculated crude age genderspecific prevalence also calculated ageadjusted prevalence level urbanization municipality residenceresults december 31 2017 algorithm identified 8 850 ms cases sensitivity 959 specificity 9997 estimated completeness ascertainment 919 overall prevalence adjusted undercount 152 per 100 000 among men 286 among women increased increasing age reached peak value 45 54year class followed progressive reduction ageadjusted prevalence residents cities 15 higher living countrysidediscussion conclusion validated algorithm based ehas identify cases ms epidemiological use prevalence ms adjusted undercount among highest italy also found prevalence higher highly urbanized areaspmid33691323 doi101159 000513763,0.0
multiple sclerosis rheumatic patients treated tumor necrosis factor alpha inhibitors singlecenter retrospective case series literature review acta reumatol port 2021 julsep 46 3 266271abstracttumor necrosis factor alpha inhibitors tnfi basilar treatments number inflammatory rheumatic conditions autoimmune phenomena de novo neuroinflammatory events already described populations tnfi conducted singlecenter retrospective study cohort rheumatic patients treated tnfi characterize neurological demyelinating inflammatory disease patients report 3 cases n 744 spondyloarthritis onset neurological manifestations occurred 37 58 years old initially presented optic neuritis neurological symptoms emerged 13 26 months starting tnfi patients discontinued treatment tnfi one resumed therapy symptomatic worsening interrupt treatment patients latter fulfilled multiple sclerosis ms mcdonald criteria 1 diagnosed relapsingremitting ms study support prior view risk diseasedependent agentdependent although causal relationship yet enlightenedpmid34628460,1.0
integrated bioinformatics analysis potential regulatory effects mir21 tcell related target genes multiple sclerosis avicenna j med biotechnol 2021 julsep 13 3 149165 doi 1018502 ajmbv13i36364abstractbackground overexpression mir21 characteristic feature patients multiple sclerosis ms involved gene regulation expression enhancement proinflammatory factors including ifn tnf following stimulation tcells via t cell receptor tcr study novel integrated bioinformatics analysis used obtain better understanding involvement mir21 development ms protein biomarker signatures rna levels drug interactions existing microarray rnaseq datasets msmethods order obtain data differentially expressed genes degs patients ms normal controls geo2r web tool used analyze gene expression omnibus geo datasets proteinprotein interaction ppi networks coexpressed degs designed using string molecular network mirnagenes drugs based differentially expressed genes created tcells ms patients identify targets mir21 may act important regulators potential biomarkers early diagnosis prognosis potential therapeutic targets msresults found seven genes nrip1 arnt kdm7a s100a10 ak2 tgfr2 il6r regulated drugs used ms mir21 finally three overlapping genes s100a10 nrip1 kdm7a identified mirnagenedrug network nineteen genes hub genes can reflect pathophysiology msconclusion findings suggest mir21 msrelated drugs can act synergistically regulate several genes existing datasets mir21 inhibitors potential used ms treatmentpmid34484645 pmcpmc8377402 doi1018502 ajmbv13i36364,0.0
supraoptic paraventricular nuclei healthy aging neurodegeneration handb clin neurol 2021 180105123 doi 101016 b9780128201077000070abstractthe supraoptic son paraventricular pvn nuclei hypothalamus undergo structural functional changes course healthy aging nuclei connections also heterogeneously affected several different neurodegenerative diseases chapter reviews involvement son pvn hypothalamicpituitary axes peptide hormones produced nuclei healthy aging neurodegeneration focus alzheimers disease ad frontotemporal dementia ftd amyotrophic lateral sclerosis progressive supranuclear palsy parkinsons disease pd dementia lewy bodies dlb multiple system atrophy huntingtons disease although agerelated changes occur several regions hypothalamus son pvn relatively preserved aging many neurodegenerative disorders aging nuclei undergo sexually dimorphic changes including changes size levels vasopressin corticotropinreleasing hormone likely due agerelated changes sex hormones contrast oxytocinergic cells circulating levels thyrotropinreleasing hormone remain stable relative resistance many forms neurodegenerative pathology also observed comparison hypothalamic brain regions mirroring pattern observed aging pathologic hallmarks ad subtypes ftd observed pvn though milder degree observed brain regions son relatively spared contrast son appears vulnerable alphasynuclein pathology dlb pd consequences alterations may help inform several physiologic changes observed aging neurodegenerative diseasepmid34225924 doi101016 b9780128201077000070,0.0
acute myelopathies associated sarscov2 infection viral immunemediated damage travel med infect dis 2021 feb 25102000 doi 101016 jtmaid2021102000 online ahead printno abstractpmid33640477 doi101016 jtmaid2021102000,0.0
cortical fractal dimension predicts disability worsening multiple sclerosis patients neuroimage clin 2021 mar 29 30102653 doi 101016 jnicl2021102653 online ahead printabstractbackground fractal geometry measures morphology brain detects cns damage aimed assess longitudinal changes brains fractal geometry predictive value disease worsening patients multiple sclerosis ms methods prospectively analyzed 146 consecutive patients relapsingremitting ms 5 years clinical brain mri 3 t assessments fractal dimension lacunarity calculated brain regions using boxcounting methods longitudinal changes analyzed mixedeffect models risk disability accumulation assessed using cox proportional hazard regression analysisresults significant decrease fractal dimension increases lacunarity different brain regions 5year followup lower cortical fractal dimension increased risk disability accumulation expanded disability status scale hr 09734 ci 0842009125 harrell c 059 wald p 0038 9hole peg test hr 09734 ci 0842009125 harrell c 059 wald p 00083 25 low contrast vision hr 04311 ci 0203509133 harrell c 058 wald p 00403 symbol digit modality test hr 2215 ci 10434705 harrell c 065 wald p 00384 ms functional composite4 hr 055 ci 03170955 harrell c 059 wald p 00029 conclusions fractal geometry analysis brain mri identified patients risk increasing disability next five yearspmid33838548 doi101016 jnicl2021102653,0.0
quantitative proteomicsbased bloodbrain barrier study biol pharm bull 2021 44 4 465473 doi 101248 bpbb2100001abstractfrom viewpoint drug discovery important issue elucidate drug permeability human central nervous system cns barriers molecular mechanisms cells forming cns barriers especially cns diseases introduced quantitative proteomics techniques bloodbrain barrier bbb study quantitatively investigated transport system human bbb clarified quantitative differences protein expression levels functions transporters receptors animals humans vitro vivo based difference absolute expression level transporters vitro vivo demonstrated drug efflux activity pglycoprotein pgp vivo bbb can accurately reconstructed vitro system mouse models also monkeys similar humans pathological conditions furthermore discovered claudin11 another tight junction molecule expressed cns barriers clarified contributes disruption cns barriers multiple sclerosis furthermore also elucidated pgp dysfunction causes excessive brain entry glucocorticoid causes nerve damage cerebral infarct can suppressed targeting abl src kinases suggest targeting tight junctions transporters important molecules cns barriers potentially lead treatment cns diseases review like introduce new cns barrier study opened quantitative proteomics researchpmid33790097 doi101248 bpbb2100001,0.0
cphycocyaninderived phycocyanobilin potential nutraceutical approach major neurodegenerative disorders covid19induced damage nervous system curr neuropharmacol 2021 apr 8 doi 102174 1570159x19666210408123807 online ahead printabstractthe edible cyanobacterium spirulina platensis chief biliprotein cphycocyanin shown protective activity animal models diverse human health diseases often reflecting antioxidant antiinflammatory effects beneficial effects cphycocyanin seem likely primarily attributable covalently attached chromophore phycocyanobilin pcb within cells biliverdin generated free heme subsequently reduced bilirubin although bilirubin can function oxidant scavenger potent antioxidant activity reflects ability inactivate isoforms nadph oxidase free bilirubin can also function agonist aryl hydrocarbon receptor ahr may explain ability promote protective treg activity cellular rodent models inflammatory disease ahr agonists also promote transcription gene coding nrf2 hence can upregulate phase 2 induction antioxidant enzymes ho1 hence proposed cphycocyanin pcb chiefly exert protective effects via inhibition nadph oxidase activity well ahr agonism induces treg activity upregulates phase 2 induction simple model may explain potent antioxidant antiinflammatory effects additionally pcb might mimic biliverdin activating antiinflammatory signaling mediated biliverdin reductase essay reviews recent research cphycocyanin pcb administered orally parenterally intranasally achieved marked protective effects rodent cell culture models ischemic stroke multiple sclerosis suggests agents may likewise protective alzheimers disease parkinsons disease covid19 neurological complicationspmid33829974 doi102174 1570159x19666210408123807,0.0
association multiple sclerosis oral health evid based dent 2021 jan 22 1 4445 doi 101038 s4143202101591abstractdata sources pubmed scopus web science medline cinahlstudy selection randomised controlled trials crosssectional studies cohort studiesdata extraction synthesis two reviewers independently extracted data using piloted forms contacted authors relevant data missing assessment quality done using newcastleottawa scale nos cohort crosssectional studies score nos ranged 19 67 considered moderate quality 89 high qualityresults seventeen studies included review 13 crosssectional four cohort seven 13 crosssectional studies scored 5 indicates poor quality four casecontrol studies moderate quality overall limited evidence patients multiple sclerosis ms dental caries gingival disease however evidence suggests patients ms risk periodontal disease poor oral hygiene evidence also suggests moderate association ms temporomandibular disorders tmd conclusions exception tmd current evidence establish association ms oral health conditions highquality evidence needed explore establish associationpmid33772137 doi101038 s4143202101591,0.0
role optical coherence tomography diagnosis afferent visual pathway problems neuroophthalmic perspective handb clin neurol 2021 17897113 doi 101016 b9780128213773000076abstractoptical coherence tomography oct noninvasive ocular imaging technique become standard tool neuroophthalmic practice specifically oct captures retinal manifestations neuroaxonal injury caused lesions along anterior posterior regions afferent visual pathway patients presenting vision loss recently advent oct angiography octa enabled evaluation choroidal retinal microvasculature thus informing understanding regarding vascular mechanisms associated optic nerve retinal injuries much longitudinal experience oct field neuroophthalmology acquired study optic neuritis caused inflammatory disorders central nervous system cns past two decades oct emerged surrogate endpoint cns neuroaxonal injury multiple sclerosis ms research trials pragmatic level oct used clinical arena diagnose associated ms neuromyelitis optica spectrum disorder nmosd myelin oligodendrocyte glycoprotein mog antibody associated disease mogad subsequent advancements sweptsource ss enhanced depth imaging edi established oct new gold standard diagnosis optic disc drusen recent studies highlighted pathognomonic oct features distinguish cases true papilledema pseudopapilledema patients presenting undifferentiated optic disc elevation preoperative oct measures neuroaxonal integrity shown prognostic value predicting postoperative visual outcomes patients compressive anterior visual pathway lesions finally oct indispensable differentiating optic neuropathies retinal diseases patients visual loss nondiagnostic fundus examination indepth discussion regarding technical aspects oct beyond scope chapter instead wish highlight value oct brings diagnosis management common neuroophthalmic conditions emphasis optic neuropathies retinal disorderspmid33832689 doi101016 b9780128213773000076,1.0
outdoor adventure programs persons multiple sclerosis review agenda future research int j ms care 2021 julaug 23 4 186192 doi 107224 153720732020066 epub 2021 aug 27abstractpersons multiple sclerosis ms often experience myriad symptoms affect functioning quality life qol although growing number nonpharmacologic interventions designed improve symptom severity interference maximize qol particular treatments limited barriers accessibility times poor patientintervention fit thus important consider alternative supplemental nonpharmacologic treatments people ms outdoor adventure programsgroupbased outdoor adventures aimed enhancing qol fostering personal growthcould one alternative supplemental approach topical review provides overview outdoor adventure programs explores current literature types programs general population medical populations examines outdoor adventure programs enhance mood functioning qol individuals ms suggests future directions research outdoor adventure programs tailored persons mspmid34483758 pmcpmc8405141 doi107224 153720732020066,0.0
anxiety depression comorbidities multiple sclerosis psychiatr danub 2021 springsummer 33 suppl 4 480485abstractmultiple sclerosis ms chronic inflammatory neurodegenerative disease accompanied number comorbidities among psychiatric ones depression anxiety occupy special place estimated prevalence anxiety ms population 221 verus 13 general population whereas prevalence anxiety levels determined various questionnaires reaches even 342 systematic literature reviews spl show considerable data variations due differences study design sample size diagnostic criteria extremely high heterogeneity i2 among conspicuous factors associated anxiety disorder ms demographic factors age gender nonsomatic depressive symptoms higher levels disability immunotherapy treatments ms type unemployment depression common psychiatric commorbidity ms lifetime risk developing depression ms patients 50 according research prevalence depression ms vary 498 589 average 237 i2973 brain versus spinal cord lesions well temporal lobe fasciculus arcuatus superior frontal superior parietal lobe lesions addition cerebral atrophy shown anatomical predictors depressive disorder ms hyperactivity hypothalamicpituitaryadrenal axis hpa consequent dexamethasoneinsupressible hypercortisolemia addition cytokine storm il6 tnf tgf1 ifn il4 present endocrine inflammatory basis development depression fatigue insomnia cognitive dysfunction spasticity neurogenic bladder pain sexual dysfunction shown additional precipitating factors development anxiety depression ms patientspmid34718269,0.0
standardizing t1w t2w ratio images trigeminal neuralgia estimate degree demyelination vivo neuroimage clin 2021 aug 21 32102798 doi 101016 jnicl2021102798 online ahead printabstractbackground novel magnetic resonance mr imaging techniques led development t1w t2w ratio images myelinsensitive maps mms estimate compare myelin content vivo currently raw image intensities conventional mr images unstandardized preventing meaningful quantitative comparisons propose improved workflow standardize mms applied patients classic trigeminal neuralgia ctn trigeminal neuralgia secondary multiple sclerosis mstn assess validity feasibility clinical toolmethods t1w t2w images obtained 17 ctn patients 17 mstn patients using 3 t scanner template images obtained icbm152 multiple sclerosis ms plaques pons labelled mstn patients patient image gaussian curve fitted histogram intensity distribution transformed match gaussian curve template imageresults standardization structural contrast patient image histogram closely resembled icbm152 template moreover reduced variability histogram peaks gray white matter patients standardization p 0001 mm intensities decreased within ms plaques compared normalappearing white matter nawm mstn patients p 0001 corresponding regions ctn patients p 0001 conclusions images intensities calibrated according mathematic relationship intensities patient image template reduced variability among histogram peaks allows interpretation tissuespecific intensity facilitates quantitative analysis resultant mms facilitate comparisons myelin content different regions brain different patients vivo mm analysis revealed reduced myelin content ms plaques compared corresponding regions ctn patients surrounding nawm mstn patients thus standardized mm serves noninvasive easilyautomated tool can feasibly applied clinical populations quantitative analyses myelin contentpmid34450507 doi101016 jnicl2021102798,1.0
cyp2r1 enzyme structure function enzymatic properties genetic polymorphism j pharm pharm sci 2021 2494112 doi 1018433 jpps31305abstractsince discovery role vitamin d metabolism significant progress made understanding gene organisation protein structure catalytic function genetic polymorphism cytochrome p450 2r1 cyp2r1 located chromosome 11p152 cyp2r1 possesses five exons unlike cyp isoforms carry nine exons cyp2r1 crystal structure displays fold pattern typical cyp protein 12 ahelices structural core bsheets mostly arranged one side heme buried interior part protein overall cyp2r1 structure adopts closed conformation b helix serving gate covering substrate access channel substrate vitamin d3 occupying position side chain pointing toward heme group liver cyp2r1 25hydroxylates vitamin d serves important determinant 25 oh d level tissue circulation substrate profile well studied inhibitor specificity cyp2r1 requires investigation exonic nonexonic single nucleotide polymorphisms snps reported cyp2r1 including cyp2r12 carrying leu99pro exchange number nonexonic snps variable functional consequences gene regulation nonexonic snp rs10741657 causal relationship diseases established including rickets ovarian cancer multiple sclerosis role cyp2r1 snps vitamin d deficiency causal link traits however remain uncertain currently studies warranted help identify possible physiological mechanisms underlying complex traitspmid33626316 doi1018433 jpps31305,0.0
identification temporal trends patients neuromyelitis optica spectrum disorder us insurance claims database j med econ 2021 apr 201 doi 101080 1369699820211917421 online ahead printabstractintroduction us claimsbased study aimed identify characterize temporal trends diagnostic pathways patients likely neuromyelitis optica spectrum disorder nmosd methods patients identified ibm marketscan commercial databases within 1 year 2 nmosd claims separated 60 days 2 transverse myelitis tm optic neuritis claims separated 60 days 1 additional symptom tm area postrema syndrome 1 nmosd claim 1 additional symptom first nmosd tm claim index date second claim diagnosis date similar methodology used temporal trend incidence prevalence analysesresults among 1901 patients nmosd 342 identified 2 nmo claims 532 tm +1 symptom 126 1 nmosd claim +1 symptom antiaquaporin4 immunoglobin g aqp4igg autoantibody tests magnetic resonance imaging used 230 719 cases respectively across cohorts 214491 multiple sclerosis ms diagnosis claims prior index date 373606 ms diagnosis 149310 ms diseasemodifying therapy dmt claims 63448 immunosuppressive therapy ist claims 1 year diagnosis time slight changes ms diagnosis claims aqp4igg autoantibody testing dmt ist use nmosd diagnosislimitations study limited information available us claims databases included potential misclassification nmosd based solely claims codes lack reimbursement aqp4igg testing insurance companiesconclusions among patients likely nmosd low aqp4igg testing rates ist use frequent ms diagnosis claims dmt use highlight need diagnostic algorithm timely treatment nmosdpmid33879033 doi101080 1369699820211917421,0.0
neurofilament light chain levels associated disease activity determined evident disease activity multiple sclerosis patients eur neurol 2021 may 2518 doi 101159 000515806 online ahead printabstractintroduction need blood biomarkers disease activity multiple sclerosis ms aim study assess relationship plasma neurofilament light chain pnfl disease activity defined concept threedomain evident disease activity neda3 methods levels pnfl simoa examined 159 ms patients analyzed relationship neda3 status absence relapse disability score worsening brain magnetic resonance activity last 12 months accuracy proposed model evaluated calculating area receiver operating characteristics roc curve pnfl cutoff evaluated nedanfl status relapse expanded disability status scale edss worsening pnfl cutoff value results levels pnfl significantly higher ms patients healthy controls p 0001 total 159 patients 80 503 achieved neda3 status 79 497 patients showed evident disease activity eda status pnfl significantly lower neda3 group eda group pnfl mean 706 pg ml standard deviation sd 237 vs pnfl mean 1304 pg ml sd 707 p 0001 roc analysis showed pnfl predicts neda3 status sensitivity specificity 805 727 respectively p 0001 nedanfl predicts neda3 status sensitivity specificity 971 829 respectively p 0001 conclusion results show pnfl levels useful biomarker disease activity determined neda status patients ms alternative brain magnetic resonance investigationpmid34034261 doi101159 000515806,0.0
cognitive performance shows domain specific associations regional cortical thickness multiple sclerosis neuroimage clin 2021 feb 24 30102606 doi 101016 jnicl2021102606 online ahead printabstractmultiple sclerosis ms patients often suffer significant cognitive impairment earlier research shown relationships regional cortical atrophy cognitive deterioration however due large number neuropsychological assessments heterogenous pattern cognitive deficits ms patients reported associations patterns also heterogenous using extensive neuropsychological battery 23 different tasks explored domain attention information processing memory spatial processing executive functioning taskspecific associations regional cortical thickness representative sample ms patients n 97 cortical regions associated multiple cognitive tasks left hemisphere predominantly located inferior insula attention p 0001 memory p 0047 spatial processing p 0004 executive functioning p 0037 gyrus frontalis superior attention p 0015 memory p 0037 spatial processing p 0033 executive functioning p 0017 temporal medial attention p 0001 memory two clusters p 0016 p 0001 executive functioning p 0016 right hemisphere detected strongest association sulcus interparietalis five cluster attention sdmt p 0003 tap_da p 0001 memory rey recall p 0013 vlmt verbal learning p 0016 spatial processing rey copy p 0001 replicated parts results independent sample 30 mildly disabled ms patients moreover comparisons 29 healthy controls showed regional associations seemed represent rather pathophysiological dependency physiological one believe results may prove useful diagnosis rehabilitation cognitive impairments may serve guidance future magnetic resonance imaging mri studiespmid33744503 doi101016 jnicl2021102606,0.0
patientreported questionnaires multiple sclerosis rehabilitation responsiveness minimal important difference french version multiple sclerosis questionnaire physiotherapists physiother can 2021 summer 73 3 226234 doi 103138 ptc20190096abstractpurpose aim study evaluate responsiveness minimal important difference mid french version multiple sclerosis questionnaire physiotherapists msqpt method distributionbased approach used patients 32 recruited inpatient outpatient settings completed msqpt hamburg quality life questionnaire multiple sclerosis haquams baseline 6 months discharge responsiveness evaluated using effect size es standardized response mean srm modified srm msrm relative efficiency msqpt haquams calculated distributionbased mid estimates calculated 033 sd standard error measurement minimal detectable change results main es ranged 041 low 123 high srm 089 269 generally higher es main msrms acceptably low 003 019 although msqpt seemed efficient haquams detecting improved activity participation less efficient identifying deterioration comparison responsiveness mid german french versions msqpt differences estimates small conclusions available evidence indicates french msqpt responsive questionnaire mids similar original german versionpmid34456439 pmcpmc8370695 doi103138 ptc20190096,0.0
poster abstracts 10th international symposium gait balance multiple sclerosis role fatigue fatigability int j ms care 2021 janfeb 23 1 4546 doi 107224 1537207323145 epub 2021 feb 23no abstractpmid33658906 pmcpmc7906032 doi107224 1537207323145,0.0
editorial int j ms care 2021 janfeb 23 1 iv doi 107224 15372073231iv epub 2021 feb 23no abstractpmid33658907 pmcpmc7906026 doi107224 15372073231iv,0.0
identifying barriers facilitators health service access encountered individuals multiple sclerosis int j ms care 2021 janfeb 23 1 3744 doi 107224 153720732020026 epub 2021 feb 23abstractbackground symptoms multiple sclerosis ms can diverse complex progressive creating need frequent longstanding health care services purpose scoping review identify barriers people ms encounter attempting access multidisciplinary health services reported facilitators better access health servicesmethods medline embase cinahl databases searched without date geographic restrictions using following terms multiple sclerosis health services accessibility health care access health care delivery delivery health care screening based exclusion criteria 23 articles included final reviewresults five main themes identified barriers facilitators accessing health services 1 information information available people ms health care provider knowledge familiarity ms 2 interactions interactions health care providers people ms social networks support people ms collaboration among health care providers 3 beliefs skills personal values beliefs perceived time travel attend appointments selfassessment symptoms needs people ms 4 practical considerations wait times physical barriers affordability services 5 nature ms complexity unpredictability disease symptoms conclusions people ms health care providers may benefit structured comprehensive msspecific education address barriers accessing health care services education can ultimately facilitate process addressing unmet health care needs contribute greater quality life people mspmid33658905 pmcpmc7906029 doi107224 153720732020026,0.0
modeling multiple sclerosis specialist nurse workforce determination optimum caseloads united kingdom int j ms care 2021 janfeb 23 1 17 doi 107224 153720732019058 epub 2020 jan 13abstractbackground estimated 100 000 people united kingdom multiple sclerosis ms patient experience outcome improved access specialist nursing service aim study perform demand modeling understand need ms nursing interventions thus inform modeling future uk ms nursing workforcemethods existing national data specific workload service data collected 163 ms specialist nurses completed questionnaire activity complexity work done left undoneresults data received across united kingdom twentynine percent respondents specialist nurses field 3 years less unpaid overtime regularly performed 834 respondents ms specialist nurse part areas patient journey areas work left undone psychological interventions physical assessments social interventions benefits recommending prescribing medicationsconclusions current recommended caseload 358 people ms per fulltime equivalent seems high considerable amount work left undone particularly psychosocial care factors travel time complexity caseload changing drug therapies societal issues benefits system contributed driving demand workloadpmid33658899 pmcpmc7906027 doi107224 153720732019058,0.0
comparison psychometric properties three fatigue scales persianspeaking patients multiple sclerosis int j ms care 2021 janfeb 23 1 815 doi 107224 153720732019051 epub 2020 feb 14abstractbackground fatigue disabling symptom patients multiple sclerosis ms although standard tool evaluate fatigue clinical settings fatigue impact scale fis fatigue severity scale fss multidimensional assessment fatigue maf scale popular instruments purpose aim study compare psychometric properties persian versions scalesmethods one hundred thirty adult patients ms 60 controls participated study completed scales two occasions 3 days apart reproducibility internal consistency evaluated intraclass correlation coefficients iccs cronbach convergent validity assessed evaluating association fatigue scales age sex expanded disability status scale edss score disease duration sleep quality dimensionality evaluated using confirmatory factor analysis acceptability knowngroup validity investigated effect size scale computedresults icc instruments 099 internal consistency 097 maf scale 093 fss 083 fis instruments showed moderatetogood correlations pittsburgh sleep quality index edss score disease duration acceptability acceptable fis three dimensions fss maf scale unidimensional scales able discriminate patients ms controlsconclusions persian version maf scale seems suitable instrument evaluate fatigue patients ms based time efficiency effect size detailed data various aspects fatiguepmid33658900 pmcpmc7906033 doi107224 153720732019051,0.0
incorporation impact clinical pharmacist hospitalbased neurology clinic treating patients multiple sclerosis int j ms care 2021 janfeb 23 1 1620 doi 107224 153720732019032 epub 2020 feb 14abstractbackground clinical pharmacists uniquely positioned assist complexities medication management patients multiple sclerosis ms objective describe clinical pharmacy services provided well provider satisfaction perceived impact incorporating clinical pharmacist ms patient caremethods study consisted retrospective medical record review provider survey conducted outpatient neurology clinic academic medical center april 2017 june 2018 electronic medical records patients documented interventions pharmacist reviewed describe clinical pharmacy services provided patients ms voluntary anonymous survey distributed neurology providers evaluate provider satisfaction perceived impact clinical pharmacist involvement ms patient careresults 64 patients identified 378 documented interventions made clinical pharmacists pharmacist interventions mostly related facilitating medication access n 208 pretreatment screening n 57 patient counseling n 51 providing drug information n 43 nine providers surveyed indicated facilitating medication access counseling patients managing drug interactions moderately important clinical pharmacy services furthermore providers surveyed strongly agreed pharmacist involvement decreased time therapy initiation provider time spent medication managementconclusions clinical pharmacists play integral role ms patient care particularly facilitating medication access prospective studies needed evaluate contribution clinical pharmacists ms patient carepmid33658901 pmcpmc7906034 doi107224 153720732019032,0.0
social cognitive theory physical activity older adults multiple sclerosis int j ms care 2021 janfeb 23 1 2125 doi 107224 153720732019071 epub 2020 feb 14abstractbackground expanding population older adults multiple sclerosis ms likely experiences many benefits physical activity pa younger middleaged adults ms however participation pa exceedingly low segment ms population study examined variables social cognitive theory sct correlates pa older adults ms inform subsequent development behavioral interventionsmethods older adults ms 60 years age n 180 completed online survey including demographic clinical characteristics sct variables exercise selfefficacy exercise goal setting social support outcome expectations pa total pa tpa moderatetovigorous pa mvpa results bivariate correlation analyses indicated sct variables significantly associated tpa mvpa p 001 hierarchical linear regression analyses indicated disability status significant correlate tpa 048 r2 023 mvpa 044 r2 019 step 1 disability selfefficacy significant correlates tpa disability 020 selfefficacy 059 r2 050 mvpa disability 016 selfefficacy 060 r2 047 step 2 disability selfefficacy exercise goal setting significant correlates tpa disability 021 selfefficacy 050 exercise goal setting 014 r2 055 mvpa disability 017 selfefficacy 051 exercise goal setting 015 r2 051 step 3conclusions results suggest behavioral interventions focusing selfefficacy exercise goal setting targets sct may appropriate increasing pa older adults mspmid33658902 pmcpmc7906028 doi107224 153720732019071,0.0
highb diffusivity ms lesions cervical spinal cord using ultrahighb dwi uhbdwi neuroimage clin 2021 mar 8 30102610 doi 101016 jnicl2021102610 online ahead printabstractpurpose purpose study investigate uhbrdwi signal white matter tracts cervical spinal cord csc compare quantitative values healthy control wm ms nawm ms wm lesionsmethods uhbrdwi experiments performed 7 ms patients recently active chronic lesions csc b 7 healthy control similar age range gender distribution ms subjects mri data acquired using clinical 3t mri system axial highb diffusion images acquired using 2d singleshot dw stimulated epi reduced fov cscdedicated 8 channel array coil highb diffusion coefficient dh estimated fitting signalb curve double singleexponential functionresults highb diffusivity dh values measured 0767 0297 103 mm2 s posterior column lesions averaged 6 ms patients 0587 103 mm2 s corticospinal tract another patient averaged dh values 7 healthy volunteers posterior lateral column 00312 00306 103 00505 00205 103 mm2 s respectively uhbrdwi signalb curves ms patients revealed noticeably behave differently healthy controls patient signalb curves decayed greater highb decay constants reach lower signal intensities relative signalb curves healthy controlsconclusion uhbdwi csc reveals marked difference signalbcurves dh values ms lesions compared nawm healthy control wm based physical principles interpret altered observations quantitative diffusion values indicative demyelination studies animal models will required fully interpret uhbdwi quantitative diffusion values demyelination remyelinationpmid33752076 doi101016 jnicl2021102610,1.0
uncovering new challenges targeting glycolysis treat th17 cellmediated autoimmunity immunometabolism 2021 3 1 e210006 doi 1020900 immunometab20210006 epub 2021 jan 22abstracttargeting glycolysis t helper 17 th17 cells presents attractive opportunity treat th17 cellmediated autoimmune diseases multiple sclerosis ms pyruvate kinase isoform 2 pkm2 glycolytic enzyme expressed t cells infiltrating central nervous system mouse model ms suggesting pkm2 modulation provide new avenue ms therapeutics recent article science signaling seki et al show pharmacological modulation pkm2 alters ameliorate disease mouse model ms results warrant consideration pkm2 modulators treat th17 cellmediated autoimmunitypmid33614166 pmcpmc7894650 doi1020900 immunometab20210006,0.0
glycosylation autoimmune diseases adv exp med biol 2021 1325205218 doi 101007 9783030701154_10abstractautoimmune diseases accompanied changes protein glycosylation immune system target tissues beststudied alteration autoimmunity agalactosylation immunoglobulin g igg characterized primarily rheumatoid arthritis ra detected also systemic lupus erythematosus sle inflammatory bowel disease ibd multiple sclerosis ms rebuilding igg nglycans ra correlates relapses remissions disease associated physiological states pregnancy also depends applied antiinflammatory therapy turn decreased core fucosylation whole pool igg nglycans serum glycomarker autoimmune thyroid diseases aitd encompassing hashimotos thyroiditis ht graves disease gd however fucosylation antithyroglobulin igg immunological marker ht elevated ht serum core fucosylation igg oligosaccharides also lowered ms sle aitd ibd chronic inflammation t lymphocytes showed reduced expression mgat5 gene encoding 1 6nacetylglucosaminyltransferase v gntv responsible 1 6branching nglycans important t cell receptor activation structural changes glycans profound effect proinflammatory activity immune cells serum immune proteins including igg autoimmunitypmid34495537 doi101007 9783030701154_10,0.0
epigenetic regulation glycosylation adv exp med biol 2021 1325173186 doi 101007 9783030701154_8abstractexpression glycosylationrelated genes glycogenes strictly regulated transcription factors epigenetic processes normal pathological conditions fact glycosylation essential mechanism proteins lipids modified perform variety biological events adapt environment interact microorganismsmany glycogenes role normal development epigenetically regulated essential studies performed brain expression glycogenes like mgat5b b4galnt1 st8sia1 control histone modifications immune system expression fut7 regulated dna methylation histone modifications present epigenetic regulation glycosylation still poorly described physiological conditions since majority studies focused cancer fact virtually types cancers display aberrant glycosylation genetic epigenetic modifications glycogenes also true many diseases inflammatory bowel disease diabetes systemic lupus erythematosus iga nephropathy multiple sclerosis cardiovascular diseasesa deeper knowledge epigenetic regulation glycogenes essential since research field helpful finding novel personalized therapeuticspmid34495535 doi101007 9783030701154_8,0.0
siponimod new view therapy secondary progressive multiple sclerosis zh nevrol psikhiatr im s s korsakova 2021 121 7 124129 doi 1017116 jnevro2021121071124abstractsiponimod selective modulator sphingosine1phosphate s1p receptors types 1 5 registered russian federation treatment patients secondary progressive multiple sclerosis spms regardless presence absence exacerbations effectiveness drug comparison placebo demonstrated patients spms international clinical trial expand phase iii review devotes actual problems treatment patients spms discusses pathophysiology multiple sclerosis progression describes peripheral central mechanisms siponimod action differences fingolimod according analysis scientific literature experimental clinical neuroimaging data presented explain reasons successful use siponimod patients spms taking account pathophysiological mechanisms development progression mechanisms drug actionpmid34460168 doi1017116 jnevro2021121071124,0.0
antidrug antibodies antibodybased therapeutics multiple sclerosis hum antibodies 2021 aug 6 doi 103233 hab210453 online ahead printabstractmultiple sclerosis major demyelinating autoimmune disease central nervous system relapsing ms can treated number approved monoclonal antibodies currently target cd20 cd25 withdrawn cd49d cd52 target potentially pathogenic memory b cell subsets perhaps functionally inhibit pathogenic t cell function consist chimeric humanized fully human antibodies however despite humanization evident monoclonal antibodies can induce binding neutralizing antibodies ranging 1 80 within year treatment importantly evident monitoring allow prediction future treatmentfailure individuals treatment cessation switching therefore potentially limiting disease breakthrough disability accumulation response covid19 pandemic need avoid hospitals shortened infusion times extended dose intervals implemented importantly subcutaneous delivery alternative treatments formulations developed allow home treatment therefore hospitalbased remote monitoring ada therefore advantageous optimize patient responses futurepmid34397407 doi103233 hab210453,1.0
ofatumumab new drug treatment multiple sclerosis zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 3743 doi 1017116 jnevro202112107237abstractrecently antibcell therapy increasingly integrated treatment multiple sclerosis ms review devoted ofatumumab new drug line ofatumumab allhuman monoclonal antibody used treat chronic leukemia binds different region binding site cd20 antibodies including small large loop cd20 receptor structure monoclonal antibody provides favorable results ms reducing frequency exacerbations risk disability progression significantly pronounced compared teriflunomide drug can used patients active relapsing ms spms exacerbations ineffectiveness firstline drugs one options secondline therapy patients highly active ms especially high risk pml transfer natalizumab well difficulties organizing intravenous courses day hospitals produced outpatient injections pmid34387444 doi1017116 jnevro202112107237,1.0
homocysteine markers endothelial dysfunction multiple sclerosis zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 9093 doi 1017116 jnevro202112107290abstractobjective identify hyperhomocysteinemia assess possible association course markers endothelial damage multiple sclerosismaterial methods analysis blood serum homocysteine content adhesion molecules specam1 matrix metalloproteinase 9 blood plasma test von willebrand factor antigen patients multiple sclerosis values indicators analyzed depending course activity demyelinating process severity neurological disorders also depending therapy receivedresults hyperhomocysteinemia found half patients multiple sclerosis significantly higher homocysteine level found male patients hyperhomocysteinemia associated activity process patients highly active multiple sclerosisconclusion results study suggest possible association hyperhomocysteinemia high process activity disease progression well mechanisms neurodegeneration determination homocysteine concentration may one potential marker predicting course diseasepmid34387453 doi1017116 jnevro202112107290,1.0
possibility using multiple sclerosisassociated variants mitochondrial genome predict development multiple sclerosis zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 6264 doi 1017116 jnevro202112107262abstractmultiple sclerosis ms chronic disease central nervous system characterized autoimmune inflammation demyelination neurodegeneration ms complex disease develops influence environmental factors genetically predisposed individuals currently 200 genetic loci associated ms identified various methods located mitochondrial dna paper collects data mtdna variants associated ms russian ethnic group shows possibility using information construct refine models predicting development mspmid34387448 doi1017116 jnevro202112107262,1.0
association hladr2related haplotype hladrb501drb11501dqb10602 patients multiple sclerosis khuzestan province iran j child neurol 2021 summer 15 3 3546 doi 1022037 ijcnv14i418795abstractobjective multiple sclerosis ms partially heritable autoimmune disease hladr2 largest identified genetic risk factor ms largest identified genetic risk factor haplotype mhc class ii hladr2 increases disease risk hladr2 distribution ms patients confirmed contradictory outcomes found moreover hladr2 effect ethnicity gender unclear data regarding hladr2 hladrb11501drb501dqb10602 association ms khuzestan province iran study aimed investigate association hladr2 ms regarding sex ethnicity provincematerials methods total 399 individuals recruited hla typing conducted using polymerase chain reaction amplification sequencespecific primers technology hladr2 association ms analyzed also probable association gender ethnicity expanded disability status scale edss ms clinical course examined using chisquare testresults hladrb501 dqb10602 common hla haplotype found patient control groups contrast drb501 + drb11501 + dqb10602 frequency low groups observed haplotypes association ms susceptibility haplotypes showed association ethnicity sex edss ms course except hladrb501 + drb11501 + dqb10602 haplotype positively associated edss steps 5 10 p0014 nonrrms p0023 conclusion association hladr2 ms susceptibility however higher hladrb501 + drb11501 + dqb10602 frequency may play role ms development also hladr2 increase significantly concerning clinical course ethnicity sex edss study supports importance replication studies susceptible loci might differ various ethnicities therefore concluded association hladr2 ms allelic haplotypic khuzestanpmid34282361 pmcpmc8272550 doi1022037 ijcnv14i418795,0.0
atypical clinical manifestations form presentation multiple sclerosis medicina b aires 2021 81 6 972977abstractthe atypical clinical features multiple sclerosis ms rarely reported suggest possibility alternative diagnosis aim describe clinical demographic characteristics ms patients debuted atypical symptoms estimate sensitivity specificity positive predictive value ppv ms diagnosis retrospective analysis clinical records performed following data recorded patients ms diagnosis according current diagnostic criteria time diagnosis type symptom onset time second relapse presence oligoclonal bands ocb cerebrospinal fluid csf radiological red flags mri descriptive inferential analysis performed using chi square test sensitivity specificity ppv calculated six hundred two patients diagnosed ms 22 365 atypical clinical presentation 545 women mean age 29 years sd 117 common atypical symptom peripheral facial palsy 27 ppv atypical onset 614 p 0001 sensitivity specificity symptoms ms diagnosis 365 19 respectively research presence atypical symptoms onset ms low diseases must excluded taking account low sensitivity specificity ppvpmid34875596,0.0
orexin hypocretin system neuropsychiatric disorders relation signs symptoms handb clin neurol 2021 180343358 doi 101016 b9780128201077000215abstracthypocretin1 2 orexin b neuropeptides exclusively produced group neurons lateral dorsomedial hypothalamus project throughout brain accordance two different hypocretin receptors also found throughout brain hypocretin system mainly involved sleepwake regulation also reward mechanisms food intake metabolism autonomic regulation including thermoregulation pain disorder strongly linked hypocretin system primary sleep disorder narcolepsy type 1 caused lack hypocretin signaling likely due autoimmune process targeting hypocretinproducing neurons however hypocretin system may also affected lesser extent less specifically various neurological disorders examples neurodegenerative diseases alzheimers huntingtons parkinsons disease immunemediated disorders multiple sclerosis neuromyelitis optica antima2 encephalitis genetic disorders type 1 diabetus mellitus praderwilli syndrome partial hypocretin deficiency may contribute sleep features disorderspmid34225940 doi101016 b9780128201077000215,0.0
driving errors predict simulated rearend collisions drivers multiple sclerosis traffic inj prev 2021 mar 1016 doi 101080 1538958820211883008 online ahead printabstractobjective drivers multiple sclerosis ms may increased crash risk however driving performance deficits contribute crashes fully understood based extant literature adjustment stimuli errors indicate failing onroad assessment study examines whether adjustment stimuli errors can detect occurrence collisions driving simulator drivers msmethods part quasiexperiment 38 participants ms 21 participants without ms completed visualcognitive driving simulator assessments also recorded adjustment stimuli maneuvers quantified participants adjustment stimuli maneuvers via initial pedal reaction time seconds time collision seconds mean speed meters per second occurrence rearend collisions collide vs collide simulated vehicle cut across lane front themresults logistic regression analyses indicated compared drivers without ms ms shorter time collision 04 p 001 95 ci 006 27 faster mean speed 132 p 04 95 ci 101 174 increased odds experiencing rearend collision receiver operating characteristic curve analyses indicated ms control groups time collision ms group auc 94 p0001 control group auc 86 p0001 mean speed ms group auc 76 p005 control group auc 78 p 005 differentiated participants collided vs collide drivers ms time collision 181 seconds 85 sensitivity 100 specificity 15 error rate mean speed 783 meters per second 77 sensitivity 76 specificity 47 error rate predicted occurrence collisions lowest error rateconclusions driving simulator assessment adjustment stimuli errors predicted occurrence rearend collisions drivers ms vs without ms driving assessors may target scenarios measure participants adjustment stimuli via time collision mean speed make decisions visualcognitive deficits driving performancepmid33688770 doi101080 1538958820211883008,0.0
disability life satisfaction neurological disorders role depression perceived cognitive difficulties gen hosp psychiatry 2021 sep 2 731623 doi 101016 jgenhosppsych202108013 online ahead printabstractbackground study assessed factors associated disability life satisfaction large cohort 2246 australian adults neurological disorders completed online survey mental health wellbeing hypothesised depressive symptoms perceived cognitive difficulties significantly associated outcomes even controlling significant demographic medical covariates eg age maritalstatus employment multimorbidity medication differences profiles four neurological subgroups ie multiple sclerosis n 738 epilepsy n 672 parkinsons disease n 263 acquired bran injury n 278 exploredmethods multiple hierarchical linear regressions run using crosssectional dataresults depressive symptoms made significant large unique contribution higher levels disability 0333 p 001 poorer life satisfaction 0434 p 001 overall sample across four neurological subgroups 0349 0513 p 001 greater perceived cognitive difficulties associated disability overall sample 0318 p 001 across neurological subgroups 0231 0354 p 001 life satisfaction epilepsy 0107 p 006 conclusions findings underscore importance managing psychological neuropsychiatric comorbidities neurological disorderspmid34508992 doi101016 jgenhosppsych202108013,0.0
comorbidities patients multiple sclerosis croatia psychiatr danub 2021 springsummer 33 suppl 4 475479abstractbackground comorbidities multiple sclerosis ms big role management chronic demyelinating neurodegenerative disorder aim study evaluate comorbidities patients ms croatiasubjects methods prospective crosssectional study carried outpatient setting tertiary healthcare centre 10 months included 101 consecutive patients ms mean age 4209 range 1977 years 75 female 26 male edss score 31 range 0070 average duration disease 1357487 range 142 years thirtysix patients treated disease modifying therapies dmts information comorbidities obtained medical interview data analysed using software package ibm corp released 2015 ibm spss statistics windows version 230 armonk ny ibm corpresults 33 n34 patients comorbidities equal number patients n34 33 just one comorbidity 176 n18 patients two comorbidities 157 n16 three comorbidities frequent comorbidity depression found 25 2475 patients 19 188 women 6 59 men followed hypertension 1287 n13 hyperlipidemia migraine found 693 n7 hypothyreosis arrhythmia 396 n4 number comorbidities found significantly increase duration ms r0232 p0037 women found significantly bigger numbers comorbidities men t259 df74 p005 older patients ms found significantly comorbidities r0335 p001 conclusions study gives insight presence comorbidities croatian patients ms connection comorbidities must considered managing patients ms comorbidity ms may also affect condition patient general also quality life requires tailored approach managementpmid34718268,1.0
assessment activity pacing relation physical activity healthrelated quality life adults multiple sclerosis foundation intervention development int j ms care 2021 sepoct 23 5 207212 doi 107224 153720732020047 epub 2021 feb 25abstractbackground activity pacing behavioral strategy coping fatigue optimizing physical activity pa levels achieving paced approach lifestyle sustainable selfregulated exercise practice optimize health wellbeing yet little known activity pacing affects pa healthrelated quality life hrqol controlling fatigue demographic characteristics time adults multiple sclerosis ms study examined natural use activity pacing associated pa hrqol time adults msmethods sixtyeight adults ms mean sd age 452 109 years completed questionnaires activity pacing fatigue pa hrqol 14 33 52 weeks rehabilitation associations variables examined using multilevel modelsresults associations found activity pacing pa 001 p 89 activity pacing hrqol 015 p 09 conclusions study provides initial understanding activity pacing relates pa hrqol people ms time indicates clear strategy among adults ms successful improving pa hrqol short long term persons ms may benefit goaldirected activity pacing interventions improve longitudinal engagement pa present study provides foundation intervention developmentpmid34720760 pmcpmc8550481 doi107224 153720732020047,0.0
multiple sclerosis 2020 un bon cru landscape multiple sclerosis changing new insights prognosis emergence artificial intelligence brain imaging technological advances challenging knowledge disease pathogenesis identification novel therapeutic pathways however 2020 will certainly remembered spread covid19 pandemic context possibility increased susceptibility severe covid19 patients multiple sclerosis rapidly become important question higher age expanded disability status scale score 6 obesity identified independent risk factors severe covid19 french multicentre observational cohort1 whereas study included 347 patients significant association diseasemodifying treatment exposure covid19 severity evidence now emerging therapies targeting cd20 might linked increased risk severe covid19 several studies aiming establish whether case ongoing manage individuals radiologically isolated syndromepeople brain mri scans compatible cns inflammation without neurological symptomsremains challenging longterm outcome diagnosis unknown multicentre radiologically isolated syndrome consortium study 2 largest longest study date included 277 individuals radiologically isolated syndrome cumulative probability clinical event 10 years 512 consistent previous publications young age spinal cord lesions identified independent predictors first clinical event novelty identification two additional risk factorsthe presence oligoclonal bands elevated igg index csf infratentorial lesionswith stepwise increase risk associated number factors probability ranging 29 individuals least one risk factor 87 four risk factors nevertheless absence results ongoing trials potential diseasemodifying drugs teris nct03122652 arise nct02739542 recommendation treat individuals radiologically isolated syndrome artificial intelligence opened new avenues medical imaging general multiple sclerosis one example deep learning approach applying convolutional neural networks 4 evaluating possibility predicting brain lesion activity without need contrast injection study conventional mri data 519 patients total 1390 enhancing lesions used train test network performance participants enhancing lesions classified 70 accuracy similarly method proposed wei colleages4 offer alternative pet scanning predict myelin content changes using multisequence quantitative mri myelin imaging 11cpib pet allows quantification myelin content changes vivo invasive injection radioactive tracer poorly suited multicentre studies deep learning approach used wei colleagues4 allowed generation synthetic images predicting myelin content changes longitudinal analysis patients multiple sclerosis providing mribased algorithms deep learning methods likely modify near future management patients multiple sclerosis well design therapeutic studies regard disease pathogenesis singlecell rnasequencing methods revealed heterogeneity oligodendroglia neurons microglia healthy multiple sclerosis tissue singlecell genetic epigenetic study wheeler colleagues5 investigated heterogeneity astrocytes multiple sclerosis tissue experimental autoimmune encephalomyelitis rodent model multiple sclerosis identified subpopulation astrocytes characterised decreased expression antioxidant transcription factor nrf2 increased expression transcription factor mafg leading repression antioxidant antiinflammatory transcriptional programmes proinflammatory astrocytes detected within active white matter lesions patients multiple sclerosis results identify astrocytes might contribute inflammation tissue damage open perspectives therapeutic candidates targeting neurotoxic astrocytic activity promoting neuroprotection multiple sclerosis major challenge irreversible disability highly correlated accumulation neuronal damage several trials proremyelinating candidates ongoing6 context negative results affinity trial effect opicinumab disability patients relapsing multiple sclerosis released ending development antilingo1 strategy bexarotene promote remyelination also trialled patients relapsing multiple sclerosis eudract 201400314599 although primary efficacy outcome reported negative drug poorly tolerated secondary outcomes suggest might promote myelin repair7 regard direct neuroprotection negative results mssmart study disappointing8 phase 2b multiarm parallelgroup doubleblind randomised placebocontrolled trial aimed evaluate three neuroprotective drugs amiloride fluoxetine riluzole selected searches research animal models clinical trials primary analysis 393 patients secondary progressive multiple sclerosis none therapeutic groups showed improvement primary outcome volumetric mri percentage brain volume change baseline 96 weeks compared placebo however despite negative result study convincingly showed value feasibility multiarm phase 2 trial designed inform go nogo decision phase 3 trials targeting neuroprotection finally results trial masitinib nct01433497 target innate immunity suggested positive effect drug versus placebo disability patients progressive multiple sclerosis9 finally exciting data behavioural interventions animal models accumulating study published earlier year 10 live imaging methods used follow oligodendrocytes individual myelin sheaths murine demyelinated motor cortex assess effect learning motor task remyelination training led increased remyelination new surviving oligodendrocytesan important result debate identity remyelinating cells adult cns study strengthens evidence role neuronal activity myelination also provides convincing demonstration timely behavioural intervention onset remyelination accelerates functional recovery enhanced remyelination em reports grants personal fees biogen novartis roche personal fees merckserono teva sanofigenzyme ad scientiam outside submitted work cl reports grants personal fees biogen personal fees merckserono roche rewind ipsen outside submitted work,1.0
genomewide crispr screening reveals nucleotide synthesis negatively regulates autophagy j biol chem 2021 may 14100780 doi 101016 jjbc2021100780 online ahead printabstractmacroautophagy hereafter autophagy process directs degradation cytoplasmic material lysosomes addition homeostatic roles autophagy undergoes dynamic positive negative regulation response multiple forms cellular stress thus enabling survival cells however precise mechanisms autophagy regulation fully understood identify potential negative regulators autophagy performed genomewide crispr screen using quantitative autophagic flux reporter gfplc3rfp identified phosphoribosylformylglycinamidine synthase pfas component de novo purine synthesis pathway one negative regulator autophagy autophagy activated cells lacking pfas phosphoribosyl pyrophosphate amidotransferase ppat another de novo purine synthesis enzyme treated methotrexate exogenous levels purines insufficient purine starvationinduced autophagy activation concomitant mtorc1 suppression profoundly suppressed cells deficient tsc2 negatively regulates mtorc1 inhibition rheb suggesting purines regulate autophagy tscrhebmtorc1 signaling axis moreover depletion pyrimidine synthesis enzymes carbamoylphosphate synthetase 2 aspartate transcarbamylase dihydroorotase cad dihydroorotate dehydrogenase dhodh activated autophagy well although mtorc1 activity altered pyrimidine shortage results suggest different mechanism autophagy induction purine pyrimidine starvation findings provide novel insights regulation autophagy nucleotides possibly role autophagy nucleotide metabolism leading developing anticancer strategies involving nucleotide synthesis autophagypmid34000301 doi101016 jjbc2021100780,0.0
morphological features jaw osteonecroses injectable drug abuse arkh patol 2021 83 6 2026 doi 1017116 patol20218306120abstractobjective determine characteristic features structure jaw bone sections patients jaw osteonecrosis caused use homemade methamphetamine hm synthesized nagai methodmaterial methods investigation material jaw sequesters resected sections 60 patients taken sanitizing surgery chronic odontogenic osteomyelitis group 1 n30 comparison group jaw osteonecrosis group 2 n30 patients group 2 confirmed using hm least 2 years investigation material selected patients found congenital acquired immunodeficiencies multiple organ failure phenomena material fixed according standard procedure sections obtained stained hematoxylin eosin massongoldner morphometry used indicators proposed american society bone mineral research histomorphometry nomenclature committee well 6 author parameters findings investigation statistically processed using statistica 100 program statsoft usa nonparametric mannwhitney testresults histoarchitectonics mandible bone matrix represented destructured devitalized tissue complex mandibular microspecimens taken group patients chronic odontogenic osteomyelitis jaws state bone matrix characterized atypical rearrangement phenomena sclerosis signs primary aseptic inflammation toxic vasculopathy fibrinoid necrosis well secondary pyonecrotic inflammation mandibular microspecimens taken hm groupconclusion characteristic morphological pattern jaw osteonecrotic injuries persons hminduced drug abuse simultaneous identification two types lesions primary lesion aseptic ossifying osteitis secondary lesion pyonecrotic inflammation phenomena toxic vasculopathy fibrinoid osteonecrosis can serve one criteria confirming active regular intake hmpmid34859982 doi1017116 patol20218306120,0.0
association vitamin d metabolism enzyme gene polymorphisms multiple sclerosis risk pilot study zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 7074 doi 1017116 jnevro202112107270abstractobjective evaluate association polymorphisms genes coding enzymes involved vitamin d metabolism cyp27b1 rs703842 cyp24a1 rs2248359 risk multiple sclerosis ms material methods ninety caucasian patients remitting ms 87 volunteers without ms born living altai region russia participated study genotyping performed taqman probe methodresults association ms genotypes alleles cyp24a1 rs2248359 found cyp27b1c rs703842 associated risk ms women tc genotype cyp27b1c rs703842 associated increased risk ms odd ratio 343 148793 p0004 tt genotype contrary protective effect susceptibility ms odd ratio 031 014072 p0005 conclusion results indicate increased risk ms female carriers tc genotype cyp27b1 rs703842 low probability contribution cyp24a1 polymorphism rs2248359 predisposition ms caucasians altai regionpmid34387450 doi1017116 jnevro202112107270,0.0
impact physical functions depressive symptoms people multiple sclerosis arq neuropsiquiatr 2021 jan 79 1 4450 doi 101590 0004282x20200099abstractbackground multiple sclerosis ms immunemediated disease affects central nervous system impact ms transcends physical functions extends psychological impairment approximately 50 people ms develop depressive symptoms lifetime depressive symptoms may predict impairment physical functions however prediction depressive symptoms based objective measures physical functions still necessaryobjective compare physical functions people ms presenting depressive symptoms identify predictors depressive symptoms using objective measures physical functionsmethods crosssectional study including 26 people ms anxiety depressive symptoms assessed beck depression inventoryii bdiii hospital anxiety depression scale hads outcomes physical functions included nnninehole ppeg ttest nhpt knee muscle strength balance control timed go test tug 6minute walk test 6mwt perceived exertion measured using borg scaleresults frequency depressive symptoms 42 people ms balance control challenging task impaired people ms presented depressive symptoms balance explain 2124 variance depressive symptoms 6mwt tug presented trend significance explaining 16 variance bdiii scoreconclusions impairment physical functions consists potential predictor depressive symptoms people ms exercise interventions aiming improvement physical functions together treatment depressive symptoms conventional medical treatment suggestedpmid33656111 doi101590 0004282x20200099,0.0
effectiveness monopolar dielectric transmission pulsed electromagnetic fields multiple sclerosisrelated pain pilot study neurologia engl ed 2021 julaug 36 6 433439 doi 101016 jnrleng201803003 epub 2020 feb 7abstractintroduction pain highly prevalent patients multiple sclerosis ms chronic 50 cases classified nociceptive neuropathic mixedtype pain affects quality life sleep activities daily living electrotherapy interesting alternative complementary treatment management pain ms new innovations constantly appearingmaterial methods study evaluates effectiveness treatment monopolar dielectric transmission pulsed electromagnetic fields pemf pain associated ms performed randomised placebocontrolled clinical trial including 24 patients assessed brief pain inventory multiple sclerosis international quality life questionnaire beck depression inventory modified fatigue impact scaleresults statistically significant improvements observed maximum mean pain scores well impact pain work personal relationships sleep rest significant differences found treatment placebo groupsconclusions treatment pemf may effective reducing pain patients ms although research necessary confirm effectiveness placebo differentiate type pain may susceptible treatmentpmid34238526 doi101016 jnrleng201803003,0.0
perceptions preferences regarding multiple sclerosis research among racial ethnic groups int j ms care 2021 julaug 23 4 170177 doi 107224 153720732019131 epub 2021 jan 12abstractbackground unclear reasons minorities historically underrepresented multiple sclerosis ms clinical trials hypothesized different perceptions preferences research participation among racial ethnic groups contribute imbalancemethods members ms minority research engagement partnership network developed webbased survey english spanish research impressions concerns preferences regarding study attributes among people ms invitations take survey distributed network members partner organizationsresults included 2599 participants ms 2111 white 215 african american 188 hispanic consistently disliked study attributes included potential harms health confusing study information compared white nonhispanic participants respectively african american odds ratio 205 p 001 hispanic 179 p 003 participants concerned used research team hispanic participants concerned research participation carrying risks legal status 170 p 001 hispanic 318 p 001 african american 551 p 001 participants likely prefer study benefit racial ethnic group top concern across groups fully informed researchconclusions found strong support research across racial ethnic groups however minority groups specific concerns regarding mistrust receiving poorquality care unemployment health insurance legal status investigators wanting recruit diverse study population advised show addressed concerns communicate research will advance science literature result better care benefits underrepresented communitiespmid34483756 pmcpmc8405146 doi107224 153720732019131,0.0
caspase11 noncanonical inflammasome novel key player murine models neuroinflammation multiple sclerosis neuroimmunomodulation 2021 may 2719 doi 101159 000516064 online ahead printabstractinflammasomes intracellular protein complexes consisting pattern recognition receptors inflammatory molecules inflamed cells response various ligands inflammasomes play pivotal role execute inflammatory responses inducing pyroptosis secretion proinflammatory cytokines interleukin il 1 il18 unlike canonical inflammasomes including nodlike receptor family inflammasomes nlrp1 nlrp3 nlrc4 absence melanoma 2 inflammasomes noncanonical inflammasomes mouse caspase11 human caspase4 5 recently discovered roles inflammatory responses poorly understood however emerging studies successfully demonstrating regulatory roles noncanonical inflammasomes inflammatory responses pathogenesis inflammatory autoimmune diseases review summarizes discusses recent studies investigating regulatory roles caspase11 noncanonical inflammasome neuroinflammation pathogenesis multiple sclerosis ms provides insight validation caspase11 noncanonical inflammasome develop novel promising therapeutics mspmid34044393 doi101159 000516064,0.0
rare clinical case comorbidity earlyonset parkinson#39 s disease remitting multiple sclerosis zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 99103 doi 1017116 jnevro202112107299abstractcomorbidities extrapyramidal disorders multiple sclerosis ms rare chance combination ms parkinsons disease pd less 1 125 million total 42 cases joint development disorders described literature described patients initial changes basal ganglia mri development ms diagnosed 18 years possible common links pathogenesis neurodegenerative disease ms well cumulative effect two diseases severity axonal degeneration neuronal loss discussed description clinical case combination early onset pd relapsingremitting multiple sclerosis presentedpmid34387455 doi1017116 jnevro202112107299,0.0
preliminary results rehabilitation intervention correction cognitive impairment patients multiple sclerosis zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 9498 doi 1017116 jnevro202112107294abstractone leading symptoms patients multiple sclerosis ms cognitive impairment often affects aspects cognition learning ability memory processing speed attention proven patients often complain difficulties multitasking choosing right words problems often underestimated various studies show regular physical activity mainly aerobic exercise can potentially improve cognitive function positive effects concentration memory multitasking described march 2019 tyumen regional center ms together clinical institute brain yekaterinburg launched clinical study methods rehabilitation cognitive disorders patients ms statistically significant improvement mocatest scores according sdmt passat data main group ms patients despite significant improvement cognitive function selfassessment mental function according msqol54mn test group patients change preliminary results suggest comprehensive wellcontrolled training program can improve cognitive abilities ms patients even short course treatmentpmid34387454 doi1017116 jnevro202112107294,0.0
relationship interpersonal depressive symptoms reduced amygdala volume people multiple sclerosis considerations clinical practice int j ms care 2021 julaug 23 4 178185 doi 107224 153720732020015 epub 2020 dec 15abstractbackground lifetime prevalence depression people multiple sclerosis ms approximately 50 compared around 15 general population relationship depression quality life people ms evidence depression may contribute disease progressionmethods crosssectional pilot study assessed association depression regional brain atrophy including amygdala hippocampal volume fortynine participants ms recruited hospital ms clinic administered center epidemiological studies depression scale revised cesdr investigate whether higher endorsements items depressive affect interpersonal symptoms associated volumetric magnetic resonance imaging measurements hippocampal amygdala atrophyresults regression analysis revealed association depressionrelated interpersonal symptoms right amygdala volume association found depression hippocampal volumeconclusions results provide preliminary support unilateral biologically based relationship right amygdala characteristic interpersonal depressive symptoms expressed people ms add growing body literature implicating regional brain atrophy msassociated depression given interpersonal subcomponent cesdr measures social functioning neural networks amygdala known implicated processing social stimuli research suggests targeted diagnosis treatments depression people ms may particularly beneficial confirmatory research relationship requiredpmid34483757 pmcpmc8405145 doi107224 153720732020015,0.0
blockade d1like dopaminergic receptors suppresses th17cell function multiple sclerosis zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 8289 doi 1017116 jnevro202112107282abstractobjective investigate direct effect d1like dopaminergic receptors antagonist th17cells function multiple sclerosis ms vitromaterial methods fortyone relapsingremitting ms patients twentyfive healthy subjects examined functional activity th17cells assessed ability produce il17 ifn peripheral blood mononuclear cells pbmcs cd4+ t cells stimulated microbeads coated anticd3 anticd28antibodies study involvement d1like dopaminergic receptors modulation th17cell function samples pbmcs cd4+ tcells cultured presence dopamine specific d1like dopaminergic receptors antagonist sch23390 cytokine levels cell culture supernatants measured elisaresults production il17 ifn stimulated pbmcs higher ms patients relapse ms patients clinical remission healthy subjects production cytokines stimulated pbmcs cd4+ tcells ms patients clinical remission healthy subjects comparable dopamine reduced production cytokines pbmcs cd4+ tcells groups blockade d1like dopaminergic receptors affect dopaminemediated cytokine suppression ms patients healthy subjects blockade d1like dopaminergic receptors directly suppressed cytokine production pbmcs cd4+ tcells ms patients healthy subjectsconclusions dopamine blockade d1like dopaminergic receptors inhibitory effect th17cell function ms activation d2like dopaminergic receptors mediate inhibitory effect dopamine th17cellspmid34387452 doi1017116 jnevro202112107282,0.0
imaging cortical multiple sclerosis lesions ultrahigh field mri neuroimage clin 2021 oct 6 32102847 doi 101016 jnicl2021102847 online ahead printabstractbackground cortical lesions abundant multiple sclerosis ms yet difficult visualize vivo ultrahigh field uhf mri 7 t provides technological advances suited optimize detection cortical lesions mspurpose provide narrative quantitative systematic review literature uhf mri cortical lesions msmethods systematic search literature uhf mri cortical lesions ms published september 2020 quantitative outcome measures included cortical lesion numbers reported using 3 t 7 t mri 7 t mri sequences along sensitivity uhf mri towards cortical lesions verified histopathologyresults 7 t mri detected average 52 26 mean 95 confidence interval cortical lesions best performing image contrast 3 t largest increase type iiiv intracortical lesion detection across studies mean cortical lesion number 17 6 per patient progressive ms cohorts approximately four times cortical lesions reported cis early rrms rrms yet difference lesion type ratio ms subtypes furthermore superiority one mri sequence another established available data postmortem lesion detection uhf mri agreed modestly pathological examinations mean pro retrospective sensitivity 33 6 71 10 respectively highest sensitivity towards type type iv lesionsconclusion uhf mri improves cortical lesion detection ms considerably compared 3 t mri particularly type iiiv lesions despite modest sensitivity 7 t mri still capable visualizing aspects cortical lesion pathology potentially aid clinicians diagnosing monitoring ms progressive ms particular however standardization acquisition segmentation protocols neededpmid34653837 doi101016 jnicl2021102847,0.0
factors affecting energy metabolism prognosis patients amyotrophic lateral sclerosis ann nutr metab 2021 aug 24 77 4 236243 doi 101159 000518908 online ahead printabstractbackground aims nutritional status factor affecting prognosis patients amyotrophic lateral sclerosis als aimed clarify factors associated hypermetabolism prognosticators alsmethods fortytwo inpatients 22 men 20 women diagnosed als according revised elescorial criteria investigated following data retrospectively analyzed anthropometric measurements blood biochemistry disease severity basal energy expenditure bee resting energy expenditure ree measured indirect calorimetry spirometry bioelectrical impedance analysis single multiple regression analysis performed examine factors affecting ree metabolic changes defined ratio ree fatfree mass ffm kaplanmeier method used examine factors associated occurrence cumulative events death tracheostomy results among 42 inpatients ree significantly higher bee indicating hypermetabolism als multiple regression analysis revealed ree ffm strongly associated skeletal muscle index 3746 1532 p 00001 percent forced vital capacity fvc 0172 0021 p 0013 moreover skeletal muscle index fvc significant prognosticators associated occurrence cumulative eventsconclusions energy metabolism elevated als respiratory status muscle mass associated hypermetabolism poor prognosis adequate nutritional support may improve outcomes als preventing deterioration respiratory status reduction muscle masspmid34515052 doi101159 000518908,0.0
treatment multiple sclerosis glatiramer acetate new look zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 5661 doi 1017116 jnevro202112107256abstractin recent years use new dosage 40 mg glatiramer acetate ga administered 3 times weekly become widespread russia drug timexon produced company biocad developed passed successful clinical trials final efficacy analysis included 150 patients treated 12 months convenience using double dose ga 40 mg registered territory russian federation two manufacturing companies cjsc biocad teva pharmaceutical enterprises ltd provenpmid34387447 doi1017116 jnevro202112107256,0.0
herpesviruses biomarkers disseminated encephalomyelitis multiple sclerosis children part ii zh nevrol psikhiatr im s s korsakova 2021 121 4 93100 doi 1017116 jnevro202112140293abstractrecently problem demyelinating diseases children still acute occurs one hand high access specificity diagnostic methods hand high morbidity children different neuroinfectious diseases can lead demyelinating diseases literature review presents currently available information autoantibodies neurospecific protein role development multiple sclerosis acute disseminative encephalitis children authors also describe experience complex etiopatogenic therapy cytoflavin use helps reduce frequency expression demyelinating process endothelium dysfunction case active herpesvirus infectionpmid34037361 doi1017116 jnevro202112140293,1.0
il27 t4730c polymorphism serology multiple sclerosis pilot study vivo 2021 sepoct 35 5 28452853 doi 1021873 invivo12572abstractbackground multiple sclerosis ms one debilitating neurological diseases young adults presence single nucleotide polymorphism promoter regions interleukin 27 gene il27 t4730c rs181206 may alter transcription production cytokine levels leading mspatients methods performed casecontrol study including 82 individuals 51 patients diagnosed ms 31 healthy controls polymerase chain reactionrestriction fragment length polymorphism used order determine genotypes il27 t4730 polymorphism enzymelinked immunosorbent assay measure serum il27 levelresults carriers t4730 polymorphism found 6fold 95 confidence intervai ci 1831963 p0002 increased risk ms univariate logistic regression analysis showed increased frequency tc4730 heterozygous genotype 392 vs 97 also c4730 allele 2745 vs 806 patients compared controls 602fold increased risk 95 ci1612246 p0006 431fold increased risk 95 ci1571187 p0002 developing ms il27 levels significantly lower patients compared controls 1235 versus 1434 pg ml p0039 without significant differences genotypes multivariate logistic analysis showed il27 t4730c polymorphism odds ratio6272 95 ci1842140 p0003 smoking odds ratio4214 95 ci1391274 p0011 represented independent risk factors msconclusion study provides possible link il27 level il27 t4730c gene polymorphism risk developing ms romanian populationpmid34410977 doi1021873 invivo12572,0.0
current future immunotherapies multiple sclerosis mo med 2021 julaug 118 4 334339abstractdespite substantial progress developing new immunotherapies multiple sclerosis ms currently available immunotherapies partially effective debilitating neurological disease thus necessitating new therapeutic approaches review immunotherapies already approved ms well relevant clinical trials present experimental approaches currently developed focused modulating functions dendritic cells regulatory t cellspmid34373668 pmcpmc8343631,1.0
allnet anatomical information lesionwise loss function integrated neural network multiple sclerosis lesion segmentation neuroimage clin 2021 oct 12 32102854 doi 101016 jnicl2021102854 online ahead printabstractaccurate detection segmentation multiple sclerosis ms brain lesions magnetic resonance images important disease diagnosis treatment challenging task lesions vary greatly size shape location image contrast objective study develop algorithm based deep convolutional neural network integrated anatomic information lesionwise loss function allnet fast accurate automated segmentation ms lesions distance transformation mapping used construct convolutional module encoded lesionspecific anatomical information overcome lesion size imbalance network training improve detection small lesions lesionwise loss function developed individual lesions modeled spheres equal size isbi2015 longitudinal ms lesion segmentation challenge dataset 19 subjects total allnet achieved overall score 9332 amongst top performing methods larger cornell ms dataset 176 subjects total allnet significantly improved voxelwise metrics dice improvement 39 353 pvalues ranging p 001 p 00001 auc voxelwise precisionrecall curve improvement 21 298 lesionwise metrics lesionwise f1 score improvement 126 298 pvalues p 00001 auc lesionwise roc curve improvement 14 200 compared leading publicly available ms lesion segmentation toolspmid34666289 doi101016 jnicl2021102854,0.0
memory processing emotional stimuli volume limbic structures pediatriconset multiple sclerosis neuroimage clin 2021 jul 9 31102753 doi 101016 jnicl2021102753 online ahead printabstractobjective limbic system involved memory processing emotional stimuli measured volume hippocampus amygdala thalamus assessed relative contribution episodic memory emotion identification pomsmethod sixtyfive poms participants mage 183 39 years 48 female 738 average disease duration 38 38 years 76 age sexmatched controls mage 181 46 years 49 female 645 completed penn computerized neurocognitive battery pcnb 59 65 poms participants 69 76 controls underwent 3 t mri scanning derived ageadjusted zscores accuracy response time rt measures episodic memory emotion identification pcnb magnetic resonance imaging mri volumetrics normalized using scaling factor computed sienax pcnb tests differed groups used multiple linear regression assess relationships regional brain volumes either episodic memory emotion identification outcomes controlling age sex accuracy rt parental educationresults poms participants slower less accurate controls episodic memory domain differ controls emotion outcomes subtest level poms participants showed reduced accuracy word memory p 002 slower performance face memory p 04 subtests poms participants smaller total regional brain volumes hippocampus amygdala thalamus p values 001 collapsing across groups hippocampal thalamic volume significant predictors word memory accuracy hippocampal volume b 024 se 010 p 02 strongly associated word memory performance thalamic volume b 016 se 005 p 003 though estimate less preciseconclusions poms participants showed reduced episodic memory performance compared controls aspects episodic memory performance associated hippocampal thalamic volume emotion identification intact despite volume loss amygdalapmid34273791 doi101016 jnicl2021102753,0.0
training caregivers compliance dysphagia recommendations tertiary multiple sclerosis rehabilitation center int j ms care 2021 sepoct 23 5 223228 doi 107224 153720732020019 epub 2021 mar 19abstractbackground dysphagia common persons multiple sclerosis ms speech language therapists give dysphagia recommendations persons ms caregivers nonadherence recommendations can increase risk aspiration investigated current compliance dysphagia recommendations among caregivers kitchen staff assessed improvement compliance increasing knowledge tailored trainingmethods observational cohort study conducted 4 weeks compliance caregivers kitchen staff rehabilitation center monitored questionnaire used assess reasons noncompliance 2hour training session provided caregivers kitchen staff improve knowledge skills compliance rate observed 1 6 months training compliance defined whether recommendations followedresults results showed significant improvement training overall compliance caregivers 58 81 p 001 improvement still observed 6 months later 80 training significant differences found compliance following recommendations p 001 consistency soup consistency liquids food preparation alertness speed amount posture supervision recommendation utensils improve p 44 compliance diet modifications made kitchen staff improved significantly 74 86 p 002 even followup 95 p 009 conclusions dysphagia training tailored needs caregivers improve knowledge significantly improves compliance dysphagia recommendations quality carepmid34720762 pmcpmc8550484 doi107224 153720732020019,0.0
assessment cerebrovascular dynamics cognitive function acute aerobic exercise persons multiple sclerosis int j ms care 2021 julaug 23 4 162169 doi 107224 153720732020003 epub 2021 jan 21abstractbackground cognitive dysfunction multiple sclerosis ms may partially stem inadequate cerebral blood flow cerebral blood flow cognitive function improve aerobic exercise healthy adults effect aerobic exercise cerebrovascular hemodynamics cognitive performance persons ms unclear acute effect aerobic exercise versus quiet rest cerebrovascular hemodynamics cognitive performance relapsingremitting ms examinedmethods sixteen adults relapsingremitting ms underwent cerebrovascular hemodynamics cognitive performance testing 2 minutes 30 minutes aerobic exercise 20minute treadmill walking 60 peak oxygen consumption timematched seated control brachial blood pressure obtained via oscillometric cuff right middle cerebral artery mca blood velocity measured via transcranial doppler used calculate mean velocity pulsatility index pi conductance carotid artery stiffness measured via ultrasonography tonometry cognitive performance accuracy reaction time assessed using modified flanker taskresults exercise elicited significant increases mean pressure carotid artery stiffness decreases mca conductance 2 minutes exercise subsided 30 minutes p 05 exercise significantly alter mca pi flanker reaction time decreased posttesting conditions p 05 condition time interactions cognitive performanceconclusions persons ms seem resilient exerciseinduced acute changes mca pi despite transient carotid stiffening potentially via reductions mca conductance data suggest changes cognitive performance acute aerobic exercise directly related transient cerebrovascular responses persons mspmid34483755 pmcpmc8405144 doi107224 153720732020003,0.0
longitudinally extensive transverse myelitis highly active relapsingremitting multiple sclerosis neurol india 2021 sepoct 69 5 14121413 doi 104103 00283886329533abstracttransverse myelitis multiple sclerosis typically short cord lesion patchy distribution rarely longitudinally extensive transverse myelitis can seen highly active disease frequent relapses recognition uncommon phenotype multiple sclerosis important treatment largely different demyelinating diseases describe patient highly active relapsingremitting multiple sclerosis interferon beta1a developed letm multiple relapsespmid34747827 doi104103 00283886329533,1.0
fully automated detection paramagnetic rims multiple sclerosis lesions 3t susceptibilitybased mr imaging neuroimage clin 2021 aug 27 32102796 doi 101016 jnicl2021102796 online ahead printabstractbackground purpose presence paramagnetic rim around white matter lesion recently shown hallmark particular pathological type multiple sclerosis lesion increased prevalence paramagnetic rim lesions associated severe disease course ms manual identification timeconsuming present aprl method automatically detect paramagnetic rim lesions 3t t2phase imagesmethods t1weighted t2flair t2phase mri brain collected 3t 20 subjects ms images processed automated lesion segmentation lesion center detection lesion labelling lesionlevel radiomic feature extraction total 951 lesions identified 113 12 contained paramagnetic rim divided data training set 16 patients 753 lesions testing set 4 patients 198 lesions fit random forest classification model training set assessed ability classify paramagnetic rim lesions test setresults number paramagnetic rim lesions per subject identified via automated lesion labelling method highly correlated gold standard count per subject r 086 95 ci 068 094 classification algorithm using radiomic features classified lesions area curve 082 95 ci 074 092 conclusion study develops fully automated technique aprl detection paramagnetic rim lesions using standard t1 flair sequences t2phase sequence obtained 3t mr imagespmid34644666 doi101016 jnicl2021102796,0.0
expert opinion polish cardiac society working group pulmonary circulation polish society rheumatology diagnosis treatment pulmonary hypertension patients connective tissue disease kardiol pol 2021 jul 6 doi 1033963 kpa20210055 online ahead printabstractsystemic connective tissue diseases ctds comprise large group diseases autoimmune nature characterized involvement multiple systems organs pulmonary hypertension ph various etiologies may develop course ctd including pulmonary arterial hypertension pah ph secondary lung disease postcapillary ph course left heart disease chronic thromboembolic pulmonary hypertension cteph addition different forms ph may coexist among patients ctd pah occurs commonly systemic sclerosis affects approximately 812 patients prognosis patients untreated pah poor particularly important identify highrisk ctdpah population perform efficient accurate diagnostics targeted therapy pulmonary arteries can introduced echocardiography used screen ph clinical echocardiographic suspicion ph always requires confirmation right heart catheterization confirmation pah enables initiation lifeprolonging pharmacological treatment group patients administered referral centers drugs available pharmacological management include endothelin receptor antagonists phosphodiesterase5 inhibitors prostacyclinspmid34227677 doi1033963 kpa20210055,0.0
development evaluation manual segmentation protocol deep grey matter multiple sclerosis towards accelerated semiautomated references neuroimage clin 2021 apr 6 30102659 doi 101016 jnicl2021102659 online ahead printabstractbackground deep grey matter dgm structures particularly thalamus clinically relevant multiple sclerosis ms however segmentation dgm ms challenging labeled msspecific reference sets needed objective evaluation training new methodsobjectives study aimed create standardized protocol manual delineations dgm ii evaluate reliability protocol multiple raters iii evaluate accuracy fastsemiautomated segmentation approach fastsurf methods standardized manual segmentation protocol caudate nucleus putamen thalamus created applied three raters multicenter 3d t1weighted mri scans 23 ms patients 12 controls intra interrater agreement assessed intraclass correlation coefficient icc spatial overlap jaccard index ji generalized conformity index cigen sparse delineations fastsurf reconstructed full segmentations accuracy assessed volumetrically spatiallyresults structures showed excellent agreement expert manual outlines intrarater ji 083 interrater icc 076 cigen 074 fastsurf reproduced manual references excellently icc 097 ji 092conclusions manual dgm segmentation protocol showed excellent reproducibility within raters moreover combined fastsurf reliable reference set dgm segmentations can produced lower workloadpmid33882422 doi101016 jnicl2021102659,0.0
accelerometer calibration importance considering functionality j meas phys behav 2021 4 1 6878 doi 101123 jmpb20200027 epub 2021 feb 25abstractpurpose compare accuracy precision hipworn accelerometer predict energy cost structured activities across motor performance disease conditionsmethods 118 adults selfidentifying healthy n 44 arthritis n 23 multiple sclerosis n 18 parkinsons disease n 17 stroke n 18 underwent measures motor performance categorized groups group 1 usual group 2 moderate impairment group 3 severe impairment participants completed structured activities wearing accelerometer portable metabolic measurement system accelerometerpredicted energy cost metabolic equivalent tasks mets compared measured mets evaluated across functional impairment disease conditions statistical significance assessed using linear mixed effect models bayesian information criteria assess model fitresults activities accelerometer counts per minute cpm 295726 less disease compared healthy predicted met bias similar across disease 049 071 027 arthritis 038 053 022 healthy 044 068 020 ms 034 058 009 parkinsons 030 054 006 stroke functional impairment graded reduction cpm activities group 1 1 215 cpm 1 129 1 301 group 2 789 cpm 695 884 group 3 343 cpm 220 466 predicted met bias revealed similar results across group 1 037 mets 052 023 group 2 044 mets 060 028 group 3 033 mets 055 013 bayesian information criteria showed better model fit functional impairment compared disease conditionconclusion using functionality improve accelerometer calibration decrease variability warrants exploration improve accelerometer prediction physical activitypmid34355136 pmcpmc8330493 doi101123 jmpb20200027,0.0
effect different administration time dosage vitamin d supplementation patients multiple sclerosis metaanalysis randomized controlled trials neuroimmunomodulation 2021 jul 2111 doi 101159 000515131 online ahead printabstractbackground despite vitamin d treatment patients multiple sclerosis ms continues controversial discrepancy outcomes according current research many systematic reviews evaluated effect vitamin d adjuvant treatment patients ms however consensus optimum administration time dosage vitamin d intake metaanalysis exploring different administration time dosage vitamin d warrantedmethods randomized controlled trials rcts effect different administration time dosage vitamin d patients ms recorded within 7 databases metaanalysis performed 2 clinical outcomes edss expanded disability status scale relapses researchresults pooled results indicated receiving different administration time dosage vitamin d adjuvant treatment significant therapeutic effect ms according edss scores relapses researchconclusion according metaanalysis administration vitamin d different dosages ranging 2 857 14 007 iu day treatment period ranging 6 24 months affect clinical outcomes edss relapses research patients ms additional rcts conducted explore whether longer duration larger dosage vitamin d without serious adverse effects might produce therapeutic effects patients mspmid34218221 doi101159 000515131,0.0
noninflammatory causes emergency consultation patients multiple sclerosis neurologia engl ed 2021 julaug 36 6 403411 doi 101016 jnrleng201802005 epub 2020 mar 31abstractobjectives describe nonrelapserelated emergency consultations patients multiple sclerosis ms causes difficulties diagnosis clinical characteristics treatments administeredmethods performed retrospective study patients attended multiple sclerosis day hospital due suspected relapse received alternative diagnosis 2year period demographic data clinical characteristics final diagnosis treatments administered evaluated patients initially diagnosed pseudorelapse ultimately diagnosed true relapse evaluated specifically exploratory analysis patients consulted noninflammatory causes compared randomly selected cohort patients true relapses attended centre periodresults study included 50 patients 33 women mean age 414 117 years four patients 8 initially diagnosed pseudorelapse later diagnosed true relapse fever vertigo main confounding factors noninflammatory causes emergency consultation neurological 435 20 patients infectious 152 7 psychiatric 109 5 vertigo 86 4 trauma 109 5 miscellaneous 109 5 conclusions msrelated symptoms constituted frequent cause noninflammatory emergency consultations close followup relapse pseudorelapse necessary detect incorrect initial diagnoses avoid unnecessary treatments relieve patients symptomspmid34238522 doi101016 jnrleng201802005,0.0
glyceryl tribenzoate food additive unique properties substitute cinnamon j clin exp immunol 2021 6 5 367372 doi 1033140 jcei060504 epub 2021 oct 20abstractcinnamon regularly used natural seasoning flavoring material throughout world eras recent laboratory studies demonstrated oral cinnamon may beneficial different neuroinflammatory neurodegenerative disorders multiple sclerosis ms parkinsons disease pd alzheimers disease ad lewy body diseases lbd however cinnamons certain limitations eg unavailability true ceylon cinnamon throughout world impurities ground cinnamon etc initiated interest among researchers find alternate cinnamon can potentially deliver efficacy diseases mentioned glyceryl tribenzoate gtb us food drug administration fda approved flavoring ingredient used food food packaging industries found similar cinnamon oral gtb capable upregulating regulatory t cells suppressing autoimmune disease process experimental autoimmune encephalomyelitis animal model ms moreover gtb cinnamon metabolite sodium benzoate nab potency attenuate neurodegenerative pathology mouse model huntington disease hd also demonstrated antiinflammatory property gtb astrocytes macrophages property also seen cinnamon metabolite sodium benzoate nab therefore made sincere attempt discuss similarities dissimilarities cinnamon gtb focus whether gtb potential considered substitute cinnamon neuroinflammatory neurodegenerative disorderspmid34723288 pmcpmc8555914 doi1033140 jcei060504,0.0
threeday dietary manipulation multiple sclerosis exercise fatigue outcomes int j ms care 2021 sepoct 23 5 199205 doi 107224 153720732020036 epub 2021 mar 10abstractbackground persons multiple sclerosis ms effect nutrition exercise performance fatigue remains unknown objective determine whether 3day diet high triglycerides fat compared 3day diet high carbohydrates carb improve fatigue exercise performance persons msmethods randomized controlled crossover design incorporated study fat versus carb submaximal cycling endurance 60 peak oxygen consumption substrate utilization fatigue 12 persons mildtomoderate ms expanded disability status scale score 2050 12 age sexmatched controlsresults differences cycling time diets either group p 29 ms group changes fatigue diets p 64 control group demonstrated increased total mental fatigue fat p 05 control group increased carbohydrate oxidation 24 rest 13 exercise carb similarly control group significantly increased fat oxidation fat 22 rest 68 exercise p 01 changes seen ms group compared controls persons ms oxidized approximately 50 less fat exercise fat p 05 conclusions neither carb fat altered submaximal exercise performance baseline fatigue ms group results suggest persons ms unable adapt dietary changes oxidize fatty acids efficiently controlspmid34720759 pmcpmc8550483 doi107224 153720732020036,0.0
brain atrophy lesion burden associated disability progression multiple sclerosis realworld dataset using t2flair neurostream msbase study neuroimage clin 2021 aug 24 32102802 doi 101016 jnicl2021102802 online ahead printabstractbackground methodological challenges limit use brain atrophy lesion burden measures followup multiple sclerosis ms patients clinical routine datasetsobjective determine feasibility t2flaironly measures lateral ventricular volume lvv salient central lesion volume sclv markers disability progression dp msmethods total 3 228 ms patients 9 msbase centers 5 countries enrolled 2 875 218 clinically isolated syndrome 2 231 relapsingremitting 426 progressive disease subtype fulfilled inclusion exclusion criteria patients scanned either 15 t 3 t mri scanners 5 750 brain scans collected index average 423 months postindex demographic clinical data collected msbase registry lvv sclv measured clinical routine t2flair imagesresults longitudinal lvv sclv analyses successful 96 scans 57 patients scannerrelated changes followup correcting age sex disease duration disability diseasemodifying therapy lvv index followup time ms patients dp n 671 significantly greater absolute lvv change compared stable n 1 501 disability improved di n 248 ms patients 20 ml vs 14 ml vs 11 ml respectively ancova p 0001 posthoc pairwise dp vs stable p 0003 dp vs di p 0002 similar ancova model also significant sclv p 003 conclusions lvvbased atrophy sclvbased lesion outcomes feasible clinically acquired t2flair scans multicenter fashion associated dp midtermpmid34469848 doi101016 jnicl2021102802,0.0
lessons learnt 101 hemispherotomies children symptomatic epilepsy part seizure outcome zh vopr neirokhir im n n burdenko 2021 85 5 1521 doi 1017116 neiro20218505115abstractobjective evaluate variables may predict outcome hemispherotomy basing retrospective study large consecutive pediatric cohort patients single institutionmaterial methods one hundred one patients refractory seizures variable decline development n78 underwent hemispherotomy med age 43 months med epilepsy history 30 months developmental pathology anatomical substrate disorder 42 patients infantile poststroke scarring gliosis origin majority 43 cases acquired etiology progressive pathology rasmussen encephalitis sturgeweber angiomatosis tuberous sclerosis etiology 16 children leftsided hemisphere impaired 54 cases contralateral anatomical potentially epileptogenic mriabnormalities noted also healthy hemisphere cases eight patients needed second surgery complete sectioning undercut commissural fibers fu known 91 patients med 15 years 73 free seizures 802 30 40 patients fu 2 years still sf 75 one redo hemispherotomies successful aedtreatment discontinued 46 cases tapered 27 patients 90 kids demonstrated improvement behavior cognitionresults conclusion developmental pathology infantile spasms younger age onset seizures negative predictors achievement sfstatus p005 neither bilateral epileptic eegsigns mriabnormalities healthy hemisphere relation outcome focal seizure onset associated positively sfstatus p 003 kids multiple lobe unilateral cd somewhat worse counterparts hemimegalencephaly acquired etiology posthemispherotomy hemiparesis either new worsening already existed one relation either age surgery age onset p 041 children leftsided lesions less successful every neurodevelopmental domain except maintaining expressive language patients relapse persisting seizures good chances become sf redoing hemispherotomy evaluated possibly incomplete hemispheric isolationpmid34713999 doi1017116 neiro20218505115,0.0
multiple sclerosis wellness shared medical appointment model pilot study int j ms care 2021 sepoct 23 5 229233 doi 107224 153720732020044 epub 2021 apr 8abstractbackground shared medical appointments smas group medical visits combining medical care patient education examined impact wellnessfocused pilot sma large multiple sclerosis ms clinicmethods reviewed data patients participated sma january 2016 june 2019 following data collected 12 months pre post sma visits demographics body mass index patientreported outcomes health care utilization data compared using wilcoxon rank sum testresults fifty adult patients mean sd age 501 123 years attended least one ms wellness sma patients private insurance 50 26 medicaid coverage common comorbidity depression anxiety 44 pre post sma outcomes showed small significant reduction body mass index 302 73 vs 288 71 p 03 patient health questionnaire9 scores decreased 73 55 51 56 p 001 number emergency department visits decreased 13 two p 0005 whereas followup visits increased attendees primary care provider 19 41 p 001 physical therapist 15 27 p 004 psychologist six 19 p 003 conclusions pilot ms wellness sma associated improved physical psychological outcomes increased lowercost health care utilization reduced acute highcost health care utilization suggesting smas may costeffective beneficial method caring patients mspmid34720763 pmcpmc8550485 doi107224 153720732020044,0.0
trend research vitamin d receptor bibliometric analysis health informatics j 2021 octdec 27 4 14604582211043158 doi 101177 14604582211043158abstractstudies vitamin d receptor vdr association multiple disorders expanding bibliometric study aims find summarize vdrrelated publications compare across various countries organizations journals demonstrate trends vdr research vosviewer excel 2019 used classify summarize web science articles 1900 mid2021 total records 8762 articles analyzed maps cocitations bibliometric keywords cooccurrence designed conclusion relative research interest published papers related vdr growing past 30 years united states america dominates research regarding vdr highest quality vdr research achieved university california system university wisconsin system harvard university j steroid biochem mol biol plos one j biol chem leading three productive journals vdr various aspects vitamin d deficiency associated disorders genetic studies regarding vdr including single nucleotide polymorphism gene variants epigenome long noncoding ribonucleic acid lncrna small nucleolar rna host gene 6 potentially recent research hotspot field moreover coronavirus disease polycystic ovary syndrome nonalcoholic fatty liver disease gut microbiota gestational diabetes systemic sclerosis chemoresistance trending medical conditions associated vdrpmid34609237 doi101177 14604582211043158,0.0
autoimmune processes involved organ system failure following infection sarscov2 adv exp med biol 2021 1318355368 doi 101007 9783030637613_21abstractduring covid19 pandemic associated high incidence transmissibility mortality chapter focuses three phases disease initial exposure initiation immune response agent finally inflammatory autoimmunelike presentation pulmonary neurological renal failure disseminated intravascular coagulation occurs small proportion patients elegant demonstration site interaction spike s protein severe acute respiratory syndrome coronavirus 2 sarscov2 causative agent covid19 ace angiotensinconverting enzyme 2 receptor cells distributed throughout body enabled research efforts develop pharmacological immune countermeasures viral phase disease chapter rapidly reviews molecular structural organization sarscov2 interaction ace2 followed discussion role major histocompatibility complex mhc recognition virus importance rapid compartmentation viral genome target cells opposed binding constant virus ace receptor discussed host factors affecting immune response virus examined subsequent inflammatory dysregulation enabling cytokine storm leading system organ failure described finally similarities clinical effects murine hepatitis virusjhm coronavirus multiorgan systems liver brain clotting cascade described perlman colleagues permit insights regarding role interaction host virus developing clinical presentation inflammatory autoimmune disorders occur multiple sclerosis neuromyelitis optica interestingly third phase covid19pmid33973189 doi101007 9783030637613_21,0.0
clinical laboratory parameters age patients diagnosed multiple sclerosis 2000 2015 neurol neurochir pol 2021 aug 6 doi 105603 pjnnsa20210055 online ahead printabstractaim study compare demographic clinical laboratory characteristics patients multiple sclerosis ms analysed based age diagnosedclinical rationale study cases ms diagnosed ages 20 40 years clinical characteristics patients ms age range rarely studiedmaterial methods 182 patients diagnosed ms 2000 2015 divided four groups age diagnosis 30 years n 62 3039 years n 54 4049 years n 27 50 years n 39 demographic clinical laboratory features age group investigated betweengroups comparisons analysedresults significant differences femaletomale ratio groups close 31 every group p 098 motor symptoms common first manifestation ms increasing age 30 193 3039 370 4049 444 50 615 visual sensory symptoms responsible nearly half first manifestations patients 30 49 affected significantly lower proportion patients oldest group p 001 median interquartile range iqr expanded disability status scale diagnosis higher advancing age 2 153 225 1535 3 235 35 35 p 001 also higher proportion patients progressive forms disease age especially primary progressive ms 00 37 148 513 p 001 median iqr time needed confirm diagnosis ms became significantly longer age increased 7 225 9 232 12 658 26 1260 months p 001 laboratory tests significant differences found rate postcontrast enhancement magnetic resonance imaging lower older age groups 632 500 316 300 p 001 conclusions clinical implications study indicates significant differences demographic clinical picture ms depending age patient diagnosis diagnostic delay older patients common problem study shows features later forms ms help inform neurologists improve time diagnosispmid34355789 doi105603 pjnnsa20210055,0.0
redesigning phd measurement course new era nursing science j prof nurs 2021 marapr 37 2 387390 doi 101016 jprofnurs202004019 epub 2020 apr 30abstractmeasurement core research process phd level students need develop indepth understanding measures relevant area work refine knowledge measurement issues traditionally measurement coursework nursing focused psychometric evaluation instruments measuring cognition behavior however age big data precision medicine translational science phd students need develop knowledge skills relevant fields collaborate experts different disciplines therefore nursing faculty need recognize stateofthescience nursing research tend variety measurement issues across spectrum operationalized concepts herein present overview learning outcomes instructional content methods delivery contemporary phdlevel course measurement nursing science also present experience design implementation evaluation novel phd measurement coursepmid33867095 doi101016 jprofnurs202004019,0.0
effectiveness physical therapy addressing sexual dysfunction individuals multiple sclerosis systematic review metaanalysis int j ms care 2021 sepoct 23 5 213222 doi 107224 153720732020039 epub 2021 mar 10abstractbackground individuals multiple sclerosis ms frequently report sexual dysfunction condition may result low sexual satisfaction decreased quality life although sexual dysfunction usually treated pharmacologically physical therapists especially trained pelvic floor physical therapy pt wellequipped address variety impairments contribute poor sexual function current evidence effectiveness pt interventions improving sexual dysfunction sexual satisfaction emotional wellbeing aspect quality life analyzedmethods pubmed cinahl pedro databases searched december 2019 articles included participants clinical diagnosis ms reported sexual dysfunction pain intercourse intervention within pt scope addressed sexual dysfunction means sds extracted study independently two authors effect sizes d 95 cis calculated within across studiesresults eight studies met inclusion criteria combined effects significant large across six studies sexual function d 082 95 ci 057106 moderate across seven studies sexual satisfaction d 065 95 ci 043087 moderately large across two studies emotional wellbeing d 078 95 ci 017140 betweengroup differences reached significance sexual satisfaction d 029 95 ci 003055 conclusions sexual function sexual satisfaction emotional wellbeing can effectively addressed various pt interventions highly effective interventions included pelvic floor muscle training mindfulness future research compare pt interventions nonpt controls determine best practice populationpmid34720761 pmcpmc8550487 doi107224 153720732020039,0.0
multiple sclerosis immunomodulatory therapies tested effectiveness covid19 neurol neurochir pol 2021 aug 4 doi 105603 pjnnsa20210051 online ahead printabstractintroduction global pandemic covid19 began wuhan china december 2019 research effective therapies conducted worldwide currently antiviral treatment many patients develop severe course disease including severe respiratory failure due similar pathomechanisms inflammation multiple sclerosis ms covid19 immunomodulatory drugs registered treatment ms study sarscov2 infection clinical trialsmaterials methods using clinicaltrialsgov found information related ongoing clinical studies potential drugs covid19 also used ms therapy outcomes several trials published pubmedncbinlmnihgovresults 18 clinical trials evaluating effectiveness safety interferon fingolimod leflunomide covid19 trial outcomes available pubmedncbinlmnihgov suggested association drug treatments improvements signs symptoms disease courseconclusion administration immunomodulatory drugs covid19 may result potential beneficial effects probably associated antiinflammatory antiviral properties research warranted confirm longterm effects immunomodulatory therapies patients covid19pmid34346052 doi105603 pjnnsa20210051,0.0
effect twelve weeks pilates training functional balance male patients multiple sclerosis randomized controlled trial j bodyw mov ther 2021 jan 254145 doi 101016 jjbmt202011003 epub 2020 nov 7abstractobjective pilates training several wellknown benefits people multiple sclerosis ms however effect functional balance unclear present study aimed evaluate effect pilates exercises functional balance male patients msmethod present parallel group randomized controlled trial 30 men ms recruited local corrective exercise clinic tehran iran randomized pilates training group n 15 control group n 15 baseline age range 2540 years disability score index 35intervention intervention group received pilates exercises including extension thoracic spine abdominal strengthening core stabilizing exercises upper lower limb posture exercises 12 weeksoutcomes functional balance assessments including bergs balance scale bbs test timed go tug test functional reach test frt measured baseline 12 weeksresults 12week followup significant betweengroup difference observed favor pilates training group functional balance scores p 005 adverse harmful events reported groupconclusion pilates training increases functional balance ms patients decreases known risk factors falls among patients group may potential reduce therapeutic costs can considered complementary therapeutic approach physical therapists corrective exercise expertspmid33714509 doi101016 jjbmt202011003,1.0
molecular effects curcumin experimental autoimmune encephalomyelitis vet res forum 2021 winter 12 1 4752 doi 1030466 vrf2019987892356 epub 2021 mar 15abstractexperimental autoimmune encephalomyelitis eae animal model multiple sclerosis ms previous studies shown myelin degradation ms eae resulted reduced expression proteins eg mbp myelin basic protein increased expression genes inos inducible nitric oxide synthase nogoa affected patients present study eae induced immunizing wistar rats n12 homogenized spinal cord guinea pig freunds complete adjuvant curcumin active ingredient turmeric antiinflammatory properties studied article study effect curcumin administration change expression mbp nogoa inos genes evaluated using rtpcr reverse transcriptionpolymerase chain reaction technique obtained results indicated concluded curcumin able improve eae increasing amount mbp gene expression reducing intensity nogoa expressionpmid33953873 pmcpmc8094149 doi1030466 vrf2019987892356,1.0
polypharmacy chronic neurological diseases multiple sclerosis dementia parkinson#39 s disease curr pharm des 2021 jul 27 doi 102174 1381612827666210728102832 online ahead printabstractpolypharmacy important aspect medication management particularly affects elderly chronically ill people patients dementia parkinsons disease pd multiple sclerosis ms high risk multimedication due complex symptomatology aim provide overview different definitions polypharmacy present current state research polypharmacy patients dementia pd ms common definition polypharmacy literature concomitant use 5 medications quantitative definition approach polypharmacy rates 50 reported patients dementia pd ms although ms patients average significantly younger dementia pd main predictor polypharmacy complex symptom profile neurological disorders potentially inappropriate medication pim drugdrug interactions poor treatment adherence severe disease course cognitive impairment hospitalisation poor quality life frailty mortality associated polypharmacy patients dementia pd ms patients polypharmacy either avoidance pim selective deprescribing substitution pim suitable drugs appropriate polypharmacy recommended achieve effective therapeutic managementpmid34323180 doi102174 1381612827666210728102832,0.0
current approaches future directions treatment mtoropathies dev neurosci 2021 apr 28116 doi 101159 000515672 online ahead printabstractthe mechanistic target rapamycin mtor kinase center evolutionarily conserved signaling pathway orchestrates cell growth metabolism mtor responds array intra extracellular stimuli turn controls multiple cellular anabolic catabolic processes aberrant mtor activity associated numerous diseases particularly profound impact nervous system mtor found two protein complexes mtor complex 1 mtorc1 2 mtorc2 governed different upstream regulators distinct cellular actions mutations genes encoding mtor regulators result collection neurodevelopmental disorders known mtoropathies disorders can affect multiple organs neuropsychiatric conditions epilepsy intellectual disability autism spectrum disorder major impact quality life neuropsychiatric aspects mtoropathies particularly challenging treat clinical setting current therapeutic approaches center rapamycin analogs drugs administered systemically inhibit mtor activity drugs show clinical efficacy adverse side effects incomplete suppression mtor targets lack specificity mtorc1 mtorc2 may limit utility increased understanding neurobiology mtor underlying molecular cellular circuit mechanisms mtorrelated disorders will facilitate development improved therapeutics animal models mtoropathies helped unravel consequences mtor pathway mutations specific brain cell types developmental stages revealing array diseaserelated phenotypes review discuss current progress potential future directions therapeutic treatment mtoropathies focus findings genetic mouse modelspmid33910214 doi101159 000515672,0.0
shared decision making disease modifying therapy families children adolescents pediatric onset multiple sclerosis j pediatr nurs 2021 oct 12 61404409 doi 101016 jpedn202109008 online ahead printabstractbackground deciding disease modifying therapy dmt treatment pediatric onset multiple sclerosis poms often presents challenge families parents often overwhelmed dmt choices desire integral part decision making process child standard approach best involve families process aim study describe experience decision making related use disease modifying therapy parents children adolescents pomsmethods research aim addressed using descriptive survey design participants recruited pediatric ms related disorders program boston childrens hospital well pediatric multiple sclerosis alliance online facebook groupresults overall fewer half parents felt satisfied dmt chose child poms 44 parental satisfaction decision making process increased high level control process p 00001 satisfaction communication p 00001 feeling supported healthcare provider p 00001 practice implications healthcare providers recognize importance role family decision making process directly impacts health outcomes open discussion time dmt education involve identification family values preferences use online decision support tools valuable role determining family preferencesconclusion opportunity healthcare providers foster shared decision making practices improve satisfaction among parents children adolescents poms healthcare providers work closely families identify incorporate personal preferences role decision making process future research include testing decision support tools decision making pomspmid34655844 doi101016 jpedn202109008,0.0
primary cardiac tumours well can prenatal diagnosis quot predictquot postnatal outcome bratisl lek listy 2021 122 5 315319 doi 104149 bll_2021_053abstractobjective primary foetal cardiac tumours rare congenital malformations can cause flow obstruction arrhythmias can lead cardiac failure hydrops death postnatal management based patients clinical hemodynamic impairmentmethods retrospectively reviewed data 20092019 gynaecology clinic also data regarding postnatal followup partner paediatric institutionresults period diagnosed six cases foetal cardiac tumours four cases multiple rhabdomyomas present three patients serious complications pre postnatally one case tumours obliterating inflow outflow left ventricle child died three months age tuberous sclerosis confirmed cases rhabdomyomas one child fibroma filling left ventricle despite uneventful prenatal period patient got postnatally symptomatic tumour considered inoperable child died age five months one case single right ventricular unspecified tumour diagnosed without complicationsconclusion prognosis closely depends early diagnosis clinical manifestations possibility surgical tumour removal necessary confirmed rhabdomyomas tests tuberous sclerosis mandatory tab 1 fig 2 ref 18 text pdf wwwelissk keywords rhabdomyoma fibroma prenatal diagnosis ultrasound tuberous sclerosispmid33848180 doi104149 bll_2021_053,0.0
neuropathic pain syndromes patients multiple sclerosis zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 2230 doi 1017116 jnevro202112107222abstractamong numerous pain syndromes ps various localizations types observed patients multiple sclerosis ms greatest attention researchers attracted neuropathic ps neuropathic ps often present already early stage ms significantly reduce quality life hinder social adaptation patients poorly respond therapy central neuropathic ps pathogenesis closely related plaques central nervous system common patients ms diagnostics neuropathic ps ms based mainly typical clinical symptoms mri neurophysiological methods data secondary importance review focuses modern concepts three main neuropathic ps ms ongoing extremity pain trigeminal neuralgia lhermittes sign clinical symptoms neuropathic ps current ideas pathogenetic mechanisms mri neurophysiological techniques data existing approaches conservative therapy surgical treatment based randomized trials data presentedpmid34387442 doi1017116 jnevro202112107222,0.0
evaluation treatment practices urinalyses urine cultures outpatient multiple sclerosis clinic int j ms care 2021 sepoct 23 5 234238 doi 107224 153720732021034 epub 2021 oct 26abstractbackground patients multiple sclerosis ms experience disease flares can precipitated presence infection discerning asymptomatic bacteriuria urinary tract infection uti patients ms complicated lower urinary tract dysfunction leading potentially inappropriate antimicrobial use study antimicrobial treatment practices positive urine cultures patients ms evaluatedmethods singlecenter retrospective study positive cultures patients ms included primary outcome proportion patients appropriately treated without antimicrobial therapy secondary end points included antimicrobial selection urinalysis positivityresults two hundred thirtysix cultures 139 patients evaluated treatment inappropriate 81 201 treated cultures 40 frequency nocturia dysuria foulsmelling urine reported patients 54 23 10 4 25 11 14 6 cultures respectively antimicrobial selected broad spectrum 35 201 17 fluoroquinolones agents used 33 35 cases 94 urinalysis sent 203 cases 86 197 84 positive least one predefined positivity criteriaconclusions urinalyses urine cultures performed frequently patients ms often independent symptoms patients ms treated asymptomatic bacteriuria higher rates general population traditional urinary symptoms may appropriate indicators infection empirical therapy uti frequently used population often resulting inappropriate broad antimicrobial therapypmid34720764 pmcpmc8550486 doi107224 153720732021034,0.0
validating atlasbased lesion disconnectomics multiple sclerosis retrospective multicentric study neuroimage clin 2021 sep 2 32102817 doi 101016 jnicl2021102817 online ahead printabstractthe translational potential mrbased connectivity modelling limited need advanced diffusion imaging part clinical protocols many diseases addition diffusion data available brain connectivity analyses rely tractography algorithms imply two major limitations first tracking algorithms known sensitive presence white matter lesions therefore leading interpretation pitfalls poor intersubject comparability clinical applications multiple sclerosis second tractography quality highly dependent acquisition parameters diffusion sequences leading tradeoff acquisition time tractography precision propose atlasbased approach study interplay structural disconnectivity lesions without requiring individual diffusion imaging multicentric setting involving three distinct multiple sclerosis datasets containing 15 t 3 t data compare atlasbased structural disconnectome computation pipeline disconnectomes extracted individual tractography explore clinical utility reducing gap radiological findings clinical symptoms multiple sclerosis results using topological graph properties showed overall atlasbased disconnectomes suitable approximations individual disconnectomes diffusion imaging smallworldness found decrease larger total lesion volumes thereby suggesting loss efficiency brain connectivity ms patients finally global efficiency created brain graph combined total lesion volume allowed stratify patients subgroups different clinical scores three cohortspmid34500427 doi101016 jnicl2021102817,0.0
central vein sign diagnostic biomarker multiple sclerosis cavsms study protocol prospective multicenter trial neuroimage clin 2021 sep 23 32102834 doi 101016 jnicl2021102834 online ahead printabstractthe specificity implementation current mribased diagnostic criteria multiple sclerosis ms imperfect approximately 1 5 individuals diagnosed ms eventually determined disease overreliance mri findings major cause ms misdiagnosis central vein sign cvs proposed mri biomarker ms lesions extensively studied numerous cross sectional studies may increase diagnostic specificity ms cvs desirable analytical measurement scalability properties central vein sign diagnostic biomarker multiple sclerosis cavsms nihsupported 2year prospective international multicenter study conducted north american imaging ms cooperative naims evaluate cvs diagnostic biomarker immediate translation clinical care study objectives include determining concordance cvs mcdonald criteria diagnose ms sensitivity cvs detect ms typical presentations specificity cvs among atypical presentations study will recruit total 400 participants 200 typical 200 atypical presentations across 11 sites t2weighted highisotropicresolution segmented echoplanar mri will acquired baseline 24 months 3tesla scanners flair images combination flair t2 will generated evaluating cvs data will processed cloudbased platform contains clinical cvs rating modules imaging quality control will conducted automated methods neuroradiologist review cvs will determined select6 select3 lesion methods following published criteria site central readers including neurologists neuroradiologists automated cvs detection algorithms incorporation cvs mcdonald criteria will tested diagnosis will adjudicated three neurologists served 2017 international panel diagnosis ms cavsms study aims definitively establish cvs diagnostic biomarker can applied broadly individuals presenting evaluation diagnosis mspmid34592690 doi101016 jnicl2021102834,0.0
deepgrai deep gray rating via artificial intelligence fast feasible clinically relevant thalamic atrophy measurement clinical quality t2flair mri multiple sclerosis neuroimage clin 2021 mar 29 30102652 doi 101016 jnicl2021102652 online ahead printabstractbackground thalamic volume loss key marker neurodegeneration multiple sclerosis ms t2flair mri common denominator clinical routine ms imaging current methods thalamic volumetry applicable itobjective develop validate robust algorithm measure thalamic volume using clinical routine t2flair mrimethods dualstage deep learning approach based 3d unet deepgrai deep gray rating via artificial intelligence created trained validated tested 4 590 mri exams 4288 2dflair 302 3dflair 59 centers 80 10 10 train validation test split training test targets first used generate thalamic masks 3d t1 images masks reviewed corrected aligned t2flair space additional validation performed assess interscanner reliability 177 subjects 15 t 3 t within one week scanrescanreliability 5 subjects scanned repositioned rescanned longitudinal dataset including assessment disability cognition used evaluate predictive value approachresults deepgrai automatically quantified thalamic volume approximately 7 s per case made publicly available accuracy t2flair relative 3d t1 first 994 r 094 p 0001 tpr 930 fpr 03 interscanner error 321 scanrescan error repositioning 043 deepgraiderived thalamic volume associated disability r 0427 p 0001 cognition r 0537 p 0001 significant predictor longitudinal cognitive decline r2 0081 p 0024 comparatively firstderived volume r2 0080 p 0025 conclusions deepgrai provides fast reliable clinically relevant thalamic volume measurement multicenter clinicalquality t2flair images indicates potential realworld thalamic volumetry well quantification legacy datasets without 3d t1 imagingpmid33872992 doi101016 jnicl2021102652,0.0
monoclonal antibody therapies rapidly progressive highly active multiple sclerosis era covid19 pandemic zh nevrol psikhiatr im s s korsakova 2021 121 7 vyp 2 3136 doi 1017116 jnevro202112107231abstractas covid19 pandemic continues reducing risk infection immunocompromised patients remains important issue patients aggressive multiple sclerosis ms require immunosuppressive therapy order control overactive autoimmune response preliminary international national trials demonstrate older age higher disability status progressive ms generally associated severe clinical course covid19 however uncertainty remains effect diseasemodifying therapies covid19 clinical presentation article pay special attention monoclonal antibodies used immune reconstitution therapy results significant changes tcell bcell repertoire based published data registries different countries attempted estimate benefits risks therapies complicated epidemiological settingpmid34387443 doi1017116 jnevro202112107231,0.0
diagnostic measures patients systemic sclerosisassociated myopathy clin exp rheumatol 2021 julaug 39 suppl 131 4 8593 epub 2021 jul 15abstractobjectives evaluate clinicoserological profile assess diagnostic parameters myopathy patients systemic sclerosis ssc associated myopathymethods explored profiles sscmyopathy patients matched nonmyopathy ssc patients well different diagnostic measures muscle affection additionally muscle performance sscmyopathy patients assessed manual muscle test 8 muscle groups mmt8 functional index2 fi2 compared patients primary myositisresults sscmyopathy patients following features occurred significantly often even bonferroni correction multiple comparisons immunosuppressive treatment 560 vs 241 p00003 elevated levels creatine kinase ck 483 vs 53 p00001 antipmscl antibodies 304 vs 4 p000048 absence rna polymerase iii antibodies 73 vs 283 p00001 mmt8 showed mild muscle weakness sscmyopathy well primary myositis patients similar age sex muscle endurance tested fi2 generally compromised cohorts yet distribution pattern affected muscle groups differed two cohortsconclusions confirmed previously described clinicserological characteristics sscmyopathy patients study suggests autoantibody profile ck levels may helpful establishing diagnosis sscmyopathy wholebody mri might accurate capture disease extent mri selected muscle groups functional muscle tests validated primary myositis perform well assessment muscle function patients sscmyopathy potential confounders skin joint cardiovascular involvement well lack sensitivity might negatively affected test performance populationpmid34323680,0.0
tech management neurological dysfunction use digital technology adv exp med biol 2021 1317131145 doi 101007 9783030611255_7abstractworldwide estimated millions individuals suffer neurological disorder can result head injuries ischaemic events stroke neurodegenerative disorders parkinsons disease pd multiple sclerosis ms problems mobility hemiparesis common patients making daily life social factors independence heavily affected current therapies aimed improving conditions often tedious nature patients often losing vital motivation positive outlook towards rehabilitation interest use digital technology neurorehabilitation skyrocketed past decade gain insight systematic review literature field conducting following preferred reporting items systematic review metaanalyses prisma guidelines three categories stroke parkinsons disease multiple sclerosis found majority literature 84 favour use digital technologies management neurological dysfunction papers taking neutral standpoint found use technologies virtual reality vr robotics wearable sensors telehealth highly accepted patients helped improve function reduced anxiety make therapy accessible patients living remote areas successful therapies used combination conventional therapies new digital technologiespmid33945135 doi101007 9783030611255_7,0.0
regulatory status pesticide residues cannabis implications medical use neurological diseases curr res toxicol 2021 2140148 doi 101016 jcrtox202102007 epub 2021 mar 1abstractmedical cannabis represents potential route pesticide exposure susceptible populations compared qualifying conditions medical use pesticide testing requirements cannabis 33 states washington dc movement disorders common neurological category qualifying conditions including epilepsy certain symptoms multiple sclerosis parkinsons disease cause symptoms leading seizures spasticity different approaches pesticide regulation implemented cannabis cannabisderived products six states imposed strictest us epa tolerances ie maximum residue levels food commodities 400 pesticidal active ingredients cannabis pesticide testing optional three states dimethomorph showed largest variation action levels ranging 01 60 ppm 5 states evaluated potential connections insecticides cannabinoids seizure using comparative toxicogenomics database twentytwo insecticides two cannabinoids 63 genes associated 674 computationally generated chemicalgenephenotypedisease cgpd tetramer constructs notable functional clusters included oxidationreduction process 183 cgpdtetramers synaptic signaling pathways 151 neuropeptide hormone activity 46 cholinergic dopaminergic retrograde endocannabinoid signaling pathways linked 10 genetic variants epilepsy patients research needed assess human health risk cannabinoids pesticides support national standard cannabis pesticide regulationspmid34308371 pmcpmc8296824 doi101016 jcrtox202102007,0.0
probiotic commensal gut microbial therapies multiple sclerosis animal models comprehensive review gut microbes 2021 jandec 13 1 1943289 doi 101080 1949097620211943289abstractthe need alternative treatments multiple sclerosis ms triggered copious amounts research microbial therapies focused manipulating microbiotagutbrain axis comprehensive review intended present systematically evaluate current clinical preclinical evidence various probiotic commensal gut microbial therapies treatments ms using bradford hill criteria bhc multiparameter assessment rubric literature searches performed identify total 37 relevant studies 6 human 31 animal including 28 probiotic therapy 9 commensal therapy studies addition presenting qualitative summaries findings therapeutic evidence bacterial formulation assessed using bhc generate summative scores scores encompassed study quality replication considerations used rank promising therapies highlight deficiencies several therapeutic formulations including vsl#3 lactobacillus paracasei bifidobacterium animalis e coli nissle 1917 prevotella histicola emerged promising contrast number therapies hindered limited evidence replicable findings criteria need addressed future studies order harness gut microbial therapies ultimately provide cheaper safer durable treatments mspmid34264791 doi101080 1949097620211943289,0.0
safety persistence dimethyl fumarate treatment relapsingremitting multiplesclerosis farm hosp 2020 dec 30 45 2 7376 doi 107399 fh11567abstractobjective dimethyl fumarate medication approved treatment relapsingremitting multiple sclerosis purpose study evaluate safety persistence dimethyl fumarate clinical practice analyze occurrence lymphopenia patients treated dimethyl fumarate period least 6 monthsmethod retrospective longitudinal observational study carried august 2015 march 2019 study cohort made patients treated dimethyl fumarate least 6 months lymphocyte counts recorded different points time pretreatment 3 6 12 months end study period evolution lymphopenia evaluated means logistic regression statistical model analysis performed relationship decreased lymphocyte count first 6 months treatment development end study grade iiiii lymphopenia necessitating discontinuation dimethyl fumarate safety indicators also evaluated including adverse events interruptions discontinuations treatment persistence determined measuring time discontinuation treatmentresults study included total 55 patients 80 female common adverse events lymphopenia 27 rubefaction 16 digestive symptoms 11 fatigue 9 headache 3 sleep disturbances 2 eleven subjects interrupted discontinued treatment study period reasons follows pregnancy 2 personal decision 2 john cunningham virus infection 1 allergy drug 2 lymphopenia 4 median duration treatment 23 months 443 months statistically significant association found lower lymphocyte count first 6 months treatment development severe lymphopenia end study 134 035260 95 ci p 0001 conclusions adverse events observed present study line reported previous analyses lymphopenia common adverse event persistence medication similar found pivotal trials significant association found decreased lymphocyte count first 6 months treatment development severe lymphopenia end study suggests connection variables instrumental able predict even prevent occurrence lymphopeniaspmid33709887 doi107399 fh11567,0.0
successful management natalizumabassociated primary central nervous system lymphoma autologous stem cell transplant curr oncol 2020 dec 30 28 1 203208 doi 103390 curroncol28010022abstractnatalizumab used secondline treatment multiple sclerosis ms reports linked natalizumab primary central nervous system lymphoma pcnsl although described management 45yearold woman balos concentric sclerosis presented dizziness vertigo accompanied dysarthria weakness left side blurred vision right eye fourth dose natalizumab magnetic resonance imaging mri brain biopsy confirmed diagnosis pcnsl patient received modified pcnsl chemotherapy matrix protocol followed highdose chemotherapy hdc supported autologous hematopoietic stem cell transplant asct consolidation therapy thirty months later still complete remission pcnsl ms case whole brain radiotherapy excluded may associated increased risk neurotoxicity ms asct preferred shown prevent disability progression less advanced ms stages patient second receive asct context option treatment preferred patient eligiblepmid33704187 doi103390 curroncol28010022,0.0
chitinase 3like 1 target antigen patients multiple sclerosis abstractautoimmunity chitinase 3like 1 chi3l1 recently reported hepatic bowel inflammatory conditions considering chi3l1 plays role prognostic biomarker multiple sclerosis ms investigated chi3l1 potential autoantigenic target disease determined serum chi3l1 autoantibodies enzymelinked immunosorbent assay elisa cohort 60 untreated ms patients different clinical forms disease 20 healthy controls hc igg levels chi3l1 similar patients relapsingremitting ms primary secondary progressive ms hc findings support role chi3l1 autoantibodies ms pathogenesis,0.0
maternal diabetes risk multiple sclerosis offspring danish nationwide registerbased cohort study abstractbackgroundprevious studies suggest 3 to10fold increased risk multiple sclerosis ms offspring mothers diabetes mellitus dm objectivesto examine ms risk offspring diabetic mothers overall according type maternal dm pregestational dm gestational dm well examine ms risk among offspring diabetic fathersmethodsthe study cohort included 1 633 436 singletons born denmark 1978 2008 ms diagnoses identified danish multiple sclerosis registry parental dm diagnoses national patient register used cox proportional hazards regression analyses calculate hazard ratios hrs 95 confidence intervals cis association parental dm ms risk offspringresultsms risk among individuals whose mothers pregestational dm 23fold increased compared among individuals nondiabetic mothers hr225 95 ci 135375 n15 ms risk statistically nonsignificant among offspring mothers gestational dm hr103 95 ci 049216 n7 among offspring diabetic fathers hr140 95 ci 078254 n11 conclusionour nationwide cohort study utilizing highquality register data denmark several decades corroborates view offspring diabetic mothers may elevated risk developing ms,0.0
neuroimaging manifestations children sarscov2 infection multinational multicentre collaborative study summarybackgroundthe cns manifestations covid19 children primarily described case reports limit ability appreciate full spectrum disease paediatric patients aimed identify enough cases evaluated aggregate better understand neuroimaging manifestations covid19 paediatric populationmethodsan international call cases children encephalopathy related severe acute respiratory syndrome coronavirus 2 sarscov2 infection abnormal neuroimaging findings made clinical history associated plasma cerebrospinal fluid data requested data reviewed central neuroradiology panel child neurologist paediatric infectious diseases expert children categorised basis time probable exposure sarscov2 addition cases excluded direct link sarscov2 infection established established alternate diagnostic cause hypothesised accepted referral centre imaging data ten countries remotely reviewed central panel five paediatric neuroradiologists consensus opinion obtained imaging findingsfindings38 children neurological disease related sarscov2 infection identified france n13 uk n8 usa n5 brazil n4 argentina n4 india n2 peru n1 saudi arabia n1 recurring patterns disease identified neuroimaging abnormalities ranging mild severe common imaging patterns postinfectious immunemediated acute disseminated encephalomyelitislike changes brain 16 patients myelitis eight patients neural enhancement 13 patients cranial nerve enhancement occur absence corresponding neurological symptoms splenial lesions seven patients myositis four patients predominantly observed children multisystem inflammatory syndrome cerebrovascular complications children less common adults significant preexisting conditions absent children favourable outcomes however fatal atypical cns coinfections developed four previously healthy children infected sarscov2interpretationacutephase delayedphase sarscov2related cns abnormalities seen children recurring patterns disease atypical neuroimaging manifestations can found recognised potentially due sarscov2 infection underlying aetiological factor studies paediatric specific cohorts needed better understand effects sarscov2 infection cns presentation longterm followup childrenfundingamerican society pediatric neuroradiology university manchester manchester uk video abstractneuroimaging manifestations children sarscov2 infection,0.0
temporal profile serum neurofilament light multiple sclerosis implications patient monitoring abstractobjectiveto understand longitudinal serum neurofilament light chain snfl patterns can inform use prognostic biomarker multiple sclerosis ms evaluate whether snfl reflects ms disease activity diseasemodifying therapy usagemethodsthis post hoc analysis longitudinal data samples advance trial nct00906399 patients relapsingremitting ms rrms snfl measured every 3months 2years every 6months 4years regression models explored snfl data predicted 4year values brain volume expanded disability status scale score t2 lesions snfl levels assessed receiving placebo peginterferon beta1a disease activityresultsbaseline snfl predictor 4year brain atrophy development new t2 lesions clinical p002 magnetic resonance imaging mri p001 outcomes improved receiving peginterferon beta1a whose snfl decreased 16pg ml 12months versus whose snfl remained 16pg ml mean snfl levels decreased peginterferon beta1atreated patients increased placebotreated patients 95 vs 68 p001 snfl higher variable patients evidence active msconclusionthese data support snfl prognostic diseasemonitoring biomarker rrms,0.0
depression multiple sclerosis across adult lifespan abstractobjectivesthe objective study examine burden depressive symptoms across adult age span people multiple sclerosis ms test relationship depressive symptoms ms characteristics vary across age groupsmethodsin analyses ms partners advancing technology health solutions ms paths network adults ms compared prevalence depression ms paths nonms controls across age evaluated effect modification age association depressive symptoms clinical neuroperformance measures via multivariableadjusted regression modelsresultsin total 13 821 individuals ms included prevalence depression higher ms versus nonms controls similar men women across age association depression processing speed pst p interaction 0009 walking speed p interaction 004 varied age example younger depressed individuals 045 standard deviation sd 95 confidence interval ci 062 029 worse pst zscores versus nondepressed younger participants whereas older depressed individuals 020 sd 95 ci 032 008 worse pst zscores versus nondepressed older participantsconclusiondepressive symptoms age considered interpreting measures walking speed cognitive function findings may implications analyses neuroperformance change,0.0
mobile health mhealth usage barriers technological considerations persons multiple sclerosis literature review jamia open 2020 dec 15 4 3 ooaa067 doi 101093 jamiaopen ooaa067 ecollection 2021 julabstractobjectives persons multiple sclerosis ms can face number potential healthcarerelated barriers mobile health mhealth technology can potentially beneficial review aimed understand frequency current uses potential barriers mhealth usage among persons msmethods query string used identify articles pubmed medline cinahl ieee xplore published english january 2010 december 2019 abstracts reviewed selected based priori inclusion exclusion criteria fiftynine peerreviewed research studies related study questions summarizedresults majority persons ms reported using smartphones although rates mhealth utilization varied widely mhealth usage grouped 3 broad categories 1 disability symptom measurement 2 interventions symptom management 3 tracking promoting adherence increasing number mhealth options certain limitations associated ms eg poor dexterity memory problems may affect usage although including persons ms design process can address issuesdiscussion given increased attention mhealth population current need telehealth home devices important persons ms healthcare providers involved development new mhealth tools ensure end product meets needs considerations addressing potential mhealth use barriers persons ms discussedpmid34514349 pmcpmc8423420 doi101093 jamiaopen ooaa067,0.0
serum ceramide levels altered multiple sclerosis abstractbackgroundsphingolipids myelin components inflammatory signaling intermediates sphingolipid metabolism may altered people multiple sclerosis pwms existing studies limited small sample sizesobjectivesto compare levels serum ceramides pwms healthy controls hcs determine whether ceramide levels correlate disability status well optical coherence tomography oct derived rates retinal layer atrophymethodswe performed targeted lipidomics analyses 45 ceramides pwms n251 hcs n68 subset pwms baseline 5year expanded disability status scale edss assessments n185 baseline serial spectraldomain oct n180 assessedresultsseveral ceramides including hexosylceramides lactosylceramides dihydroceramides altered pwms compared hcs higher levels cer160 associated higher odds edss worsening 5years univariable odds ratio 384 95 confidence interval ci 1411043 multivariable analyses accounting age sex race or297 95 ci103859 1ng ml higher concentration hexcer220 dhhexcer220 associated accelerated rates m year ganglion cell+inner plexiform layer 01380053 p001 01580053 p0003 respectively peripapillary retinal nerve fiber layer thinning 03050107 p0004 03580106 p0001 respectively conclusionceramide levels altered pwms may associated retinal neurodegeneration physical disability,1.0
evidence subclinical quantitative retinal layer abnormalities aqp4igg seropositive nmosd abstractbackgroundprior studies suggested subclinical retinal abnormalities may present aquaporin4 immunoglobulin g aqp4igg seropositive neuromyelitis optica spectrum disorder nmosd absence clinical history optic neuritis objectiveour aim compare retinal layer thicknesses fovea surrounding macula aqp4igg+nmosd eyes without history aqp4nonon healthy controls hc methodsin singlecenter crosssectional study 83 aqp4nonon 154 hc eyes studied spectraldomain optical coherence tomography oct resultstotal foveal thickness differ aqp4nonon hc eyes aqp4nonon eyes exhibited lower outer nuclear layer onl inner photoreceptor segment thickness fovea onl 401203 m p0049 032014 m p0029 surrounding macula onl 198095 m p0037 016007 m p0023 compared hc macular retinal nerve fiber layer rnfl 134051 m p0009 ganglion cell+inner plexiform layer gcipl 244093 m p0009 thicknesses also lower aqp4nonon compared hc eyes results similar sensitivity analyses restricted aqp4igg+patients never experienced either eyeconclusionsaqp4nonon eyes exhibit evidence subclinical retinal ganglion cell neuronal axonal loss well structural evidence photoreceptor layer involvement findings support subclinical anterior visual pathway involvement may occur aqp4igg+nmosd,0.0
differentiation relapsingremitting secondary progressive multiple sclerosis magnetic resonance spectroscopy study based machine learning introduction magnetic resonance imaging mri important tool diagnosis followup multiple sclerosis ms discrimination relapsingremitting ms rrms secondary progressive ms spms clinically difficult developing proposal presented study contribute process objective study aimed ensure automatic classification healthy controls rrms spms using mr spectroscopy machine learning methods methods mr spectroscopy mrs performed total 91 participants distributed healthy controls n30 rrms n36 spms n25 firstly mrs metabolites identified using signal processing techniques secondly feature extraction performed based mrs spectra nacetylaspartate naa significant metabolite differentiating ms types lastly binary classifications healthy controlsrrms rrmsspms carried according features obtained support vector machine algorithm results rrms cases differentiated healthy controls 85 accuracy 9091 sensitivity 7778 specificity rrms spms classified 8333 accuracy 8181 sensitivity 8571 specificity conclusions combined analysis mrs computeraided diagnosis may useful complementary imaging technique determine ms types keywords multiple sclerosis multiple sclerosis relapsingremitting multiple sclerosis chronic progressive magnetic resonance spectroscopy machine learning,0.0
pharmacological treatment central neuropathic pain consensus brazilian academy neurology background central neuropathic pain cnp often refractory available therapeutic strategies evidencebased treatment options many patients neuropathic pain diagnosed treated properly thus consensusbased recommendations adapted available drugs country necessary guide clinical decisions objective develop recommendations treatment cnp brazil methods systematic review metaanalysis specialists opinions considering efficacy adverse events profile cost drug availability public health results fortyfour studies cnp treatment found 20 included qualitative analysis 15 quantitative analysis medications classified first second thirdline treatment based systematic review metaanalysis expert opinion firstline treatment gabapentin duloxetine tricyclic antidepressants included secondline venlafaxine pregabalin cnd secondary spinal cord injury lamotrigine cnp stroke association firstline drugs weak opioids particular tramadol refractory patients strong opioids methadone oxycodone cannabidiol delta9tetrahydrocannabinol classified thirdline treatment combination first secondline drugs central nervous system cns multiple sclerosis dronabinol conclusions studies address treatment cns scarce heterogeneous significant part recommendations based experts opinions cnp approach must individualized taking account availability medication profile adverse effects including addiction risk patients comorbidities,0.0
identification regulatory t cell molecules associated severity multiple sclerosis abstractbackgroundregulatory cd4+ t cells tregs exhibit functional alterations patients multiple sclerosis ms transforming growth factor tgf key regulator treg development functionobjectivethe objective study determine whether expression functionally relevant tgfregulated molecules altered tregs patients msmethodsexpression nine treg markers analyzed multicolor flow cytometry cd4+ t cells treg subpopulations 31 untreated ms patients age sexmatched healthy donors hds correlations treg marker expression clinical variables soughtresultsexpression transcription factor helios defines thymicderived tregs decreased treg subpopulation frequency peripherally generated tregs increased patients ms particularly patients progressive ms low frequencies thymicderived tregs associated magnetic resonance imaging mri lesionburden high relapse rate four surface markers associated tgf signaling abca1 btla dnam1 garp differentially expressed tregs patients ms hds expression levels cd73 cd103 abca1 par2 showed strong correlations disease severityconclusionwe identified novel markers abnormally expressed tregs patients ms detect patients severe disease,0.0
expanding spectrum opportunistic infections associated dimethyl fumarate abstractbackgroundonly progressive multifocal leukoencephalopathy pml currently described dimethyl fumarate dmf prescribing informationobjectivesto describe opportunistic infections ois pml reported association dmfmethodsthe fda adverse event reporting system faers medical literature searchedresultswe retrieved 34 cases serious ois causal association dmf including 11 central nervous system cns infections 23 extracns infections six ois occurred normal circulating absolute lymphocyte counts median latency dmf initiation 13months variableconclusiondmf associated development ois require invasive diagnostic therapeutic procedures patients monitored ois treated dmf regardless circulating absolute lymphocyte counts,0.0
functional brain network organization measured magnetoencephalography predicts cognitive decline multiple sclerosis abstractbackgroundcognitive decline remains difficult predict structural brain damage fully explain extensive heterogeneity found ms patientsobjectiveto investigate whether functional brain network organization measured magnetoencephalography meg predicts cognitive decline ms patients 5 years explore value beyond structural pathologymethodsrestingstate meg recordings structural mri neuropsychological assessments analyzed 146 ms patients 100 patients 5year followup neuropsychological assessment network properties minimum spanning tree ie backbone functional brain network indicating network integration overload related baseline longitudinal cognition correcting structural damageresultsa integrated beta band network ie smaller diameter less integrated delta band network ie lower leaf fraction predicted cognitive decline 5 years radj215 independent structural damage crosssectional analyses showed less integrated network eg lower tree hierarchy related worse cognition independent frequency bandconclusionsthe level functional brain network integration independent predictive marker cognitive decline addition severity structural damage work thereby indicates promise megderived network measures predicting disease progression ms,0.0
clinical significance single cerebrospinal fluid immunoglobulin band retrospective study abstractbackgroundto demonstrate inflammatory process central nervous system presence least two immunoglobulin ig bands cerebrospinal fluid csf required far presence single abnormal ig band considered negativeobjectivethe objective assess retrospectively significance single csf ig band clinical practicemethods resultsout 10 286 csf analyses retained 214 results single ig inflammatory neurological disorder diagnosed 41 patientsconclusiondespite modest sensitivity presence single csf ig band may biomarker inflammatory mechanism may prompt clinician repeat analysis clinical context remains suggestive,0.0
telemedicine neurology current evidence background telemedicine first introduced neurology tool facilitate access acute stroke treatment recently evidence emerged use telemedicine several areas neurology advent covid19 pandemic need social isolation brazilian authorities expanded regulation use telemedicine thus allowing treatment many patients neurological diseases conducted less risk sarscov2 contamination objective study aimed critically review current evidence use efficacy safety usefulness telemedicine neurology methods review pubmed indexed articles carried searching terms telemedicine headache multiple sclerosis vestibular disorders cerebrovascular diseases epilepsy neuromuscular diseases dementia movement disorders relevant studies areas critically analyzed results several articles found analyzed areas neurology main described contributions telemedicine diagnosis treatment neurological conditions presented indicating great potential use type assistance fields conclusion current evidence supports teleneurology can tool increase care patients suffering neurological diseases,0.0
acute disseminated encephalomyelitis covid19 presentation two cases review literature background neurological manifestations covid19 still incompletely understood neurological manifestations may due direct viral effect neurons glial cells immunemediated response virus hypercoagulable state associated endothelial damage well severe systemic disease prolonged intensive care unit stay objective describe two patients severe sarscov2 infection delayed recovery consciousness sedation withdrawal mri disclosed multifocal white matter brain lesions compatible diagnosis acute disseminated encephalomyelitis methods observational report two cases severe covid19 infection patients two tertiary hospitals paulo brazil results patients underwent neurologic systemic evaluation delayed awakening sedation withdrawal mri displayed multifocal centrum semiovale lesions suggestive demyelinating inflammation cerebrospinal fluid csf polymerase chain reaction pcr sarscov2 negative cases conclusion recurrent pattern multifocal white matter lesions can occur covid19 patients possibly associated delayed awakening additional studies necessary elucidate role viral infection inflammatory immunemediated associated changes neurological manifestations covid19,1.0
oral nomegestrol acetate transdermal 17betaestradiol preventing postpartum relapses multiple sclerosis popartmus study abstractbackgroundsex steroids explain course multiple sclerosis ms pregnancyobjectiveto compare annualized relapse rate arr 12weeks postpartum women treated nomegestrol acetate nomac 17betaestradiol e2 versus placebomethodspopartmus randomized proofofconcept trial women ms receiving oral nomac 10mg day transdermal estradiol 75g week placeboresultsrecruitment stopped prematurely due slow inclusions n202 treatment effect observed arr 12weeks sex steroids090 058139 placebo097 063150 p079 conclusionpopartmus failed showing efficacy nomace2 combination preventing postpartum relapses,0.0
multifocal visual evoked potential evaluation diagnosis acute optic neuritis prediction visual outcome ganglion cell layer thinning following optic neuritis abstractbackgroundwhile damage optic nerve following optic neuritis readily quantifiable evaluation prognosis visual function neuroaxonal loss acute challengingobjectivethe objective study investigate value multifocal visual evoked potential mfvep acute diagnostically acute prognostically visual outcome subsequent ganglion cell inner plexiform layer thickness gcliplt methodsa prospective cohort study mfvep fullfield visual evoked potential ffvep acute unilateral onset31days conducted comparisons healthy controls n30 association analysis followup optical coherence tomography oct measurements gcliplt visual function sloan lowcontrast visual acuity lcva conductedresultsseventynine patients included mean 17days onset excluding measurements conduction block ffvep n54 mfvep n44 showed sensitivities 89 84 specificity 97 65 79 patients reexamined mean 200days followup mfvep amplitude latency intereye asymmetry acute correlated gcliplt r0587 spearmans 0597 p0001 mfvep amplitude correlated lcva intereye asymmetry followup r0421 p0001 mfvep latency notconclusionmfvep may support prognostic evaluation acute patients prove valuable future neuroprotective remyelinating trials acute increase diagnostic value mfvep ffvep may limited due widespread conduction block,1.0
accurate classification secondary progression multiple sclerosis using decision tree abstractbackgroundthe absence reliable imaging biological markers phenotype transition multiple sclerosis ms makes assignment current phenotype status difficultobjectivethe authors sought determine whether clinical information can used accurately assign current disease phenotypesmethodsdata clinical visits 14 387 ms patients sweden collected classifying algorithms based several demographic clinical factors examined results obtained best classifier predicting neurologist recorded disease classification replicated independent cohort british columbia compared previously published algorithm clinical judgment three neurologistsresultsa decision tree classifier containing recently available expanded disability scale status score age obtained 893 95 confidence intervals cis 888898 classification accuracy defined concordance latest reported status validation independent cohort resulted 820 95 ci 810831 accuracy previously published classification algorithm slight modifications achieved 778 95 ci 771784 accuracy complete patient history 100 patients three neurologists obtained 843 accuracy compared 85 classifier using dataconclusionthe classifier can used standardize definitions disease phenotype across different cohorts clinically model assist neurologists providing additional information,0.0
quantifying cognition fatigue enhance sensitivity edss relapses abstractbackgroundcognition affected relapses persons multiple sclerosis pwms yet expanded disability status scale edss readily detect cognitive changesobjectivethe objective study improve detection cognitive decline relapses incorporating symbol digit modalities test sdmt cerebral functional system score cfss edssmethodsthis prospective study recruited pwms three dedicated ms centers subjects edss sdmt fatigue severity scale fss administered subjects experiencing relapse assigned relapse group rg matched controls larger cohort assigned stable group sg rg sg subjects underwent evaluation relapse 3months later main outcomes modified cfss mcfss modified edss medss incorporating sdmt fss accounting cognitive performance fatigue rating relapseresultsthe full cohort included 592 subjects 80 qualified rg 72 matched sg mcfss significantly higher cfss baseline median2 vs median0 p0001 relapse median2 vs median1 p0001 medss higher edss median 30 vs 25 p002 relapse 35 rg subjects 438 higher medss edss relapseconclusionthis study demonstrates incorporating sdmt fss improves accuracy edss accounting cognitive changes relapse activity,0.0
creb coactivator crtc2 plays crucial role endothelial function camp pathway known stabilize endothelial barrier function maintain vascular physiology family campresponse element binding creb regulated transcription coactivators crtc 13 activate transcription targeting basic leucine zipper domain creb crtc2 master regulator glucose metabolism liver adipose tissue however role crtc2 endothelium remains unknown aim study evaluate effect crtc2 endothelial function focused effect crtc2 endothelial cells relationship p190rhogapa examined effect crtc2 endothelial function using mouse aorta ring assay ex vivo photothrombotic stroke endothelial cellspecific crtc2knockout male mice vivo crtc2 highly expressed endothelial cells related angiogenesis among crtc13 crtc2 activated ischemic conditions endothelial cells crtc2 maintained endothelial barrier function p190rhogapa expression ser171 pivotal regulatory site crtc2 intracellular localization ser307 functioned crucial phosphorylation site endothelial cellspecific crtc2knockout mice showed reduced angiogenesis ex vivo exacerbated stroke via endothelial dysfunction impaired neurologic recovery via reduced vascular beds vivo findings suggest crtc2 plays crucial protective role vascular integrity endothelium via p190rhogapa ischemic conditionssignificance statement previously role crtc2 endothelial cells unknown study firstly clarified crtc2 expressed endothelial cells among crtc13 crtc2 related endothelial function importantly crtc2 activated ischemic conditions endothelial cells maintained endothelial barrier function p190rhogapa expression ser307 crtc2 functioned crucial phosphorylation site endothelial cellspecific crtc2knockout mice showed reduced angiogenesis ex vivo exacerbated stroke via endothelial dysfunction impaired neurologic recovery via reduced vascular beds vivo results suggested crtc2 maybe potential therapeutic target reducing bloodbrain barrier bbb damage improving recovery,0.0
youth multiple sclerosis low levels fitness abstractbackgroundmoderate vigorous physical activity associated improved outcomes youth multiple sclerosis ms physical fitness may also influence disease health outcomes populationobjectivesto determine differences physical fitness youth ms healthy controls hc examine relationships physical fitness physical activity pa level fatigue depression disease activity youth ms hcmethodsyouth ms n19 hc n21 completed tests establishing cardiorespiratoryfitness vo2peak endurance via 2minute walk test musculoskeletal strength via grip strength gs questionnaires determined fatigue depression pa levels weekly pa level determined accelerometry tests differences correlational analyses used evaluate physical fitnessresultsyouth ms lower vo2peak u279 p00001 endurance t26 p002 higher body mass index bmi t59 p0001 hc higher vo2peak associated higher moderate vigorous paaccelerometer hc spearmanrho05 p003 youth ms spearmanrho05 p006 lower vo2peak gs associated higher disability spearmanrho06 p003 relapses ms spearmanrho052 p004 conclusionsyouth ms lower levels fitness compared hc higher levels fitness associated lower disease activity disability youth ms,0.0
restless legs syndrome willisekbom disease multiple sclerosis contributing factor anxiety disability sleep disorder quality life background restless legs syndrome rls one common burdensome sleep disorders course multiple sclerosis ms objective evaluate common msrelated symptoms consequences groups without rls assess association quality life determinants rls symptom severity methods according rls status 46 relapsingremitting ms patients divided msrls+ n19 msrls groups n27 specific questionnaires administered assess patients healthrelated quality life hrqol fatigue levels sleep quality daily sleepiness anxiety depression symptoms functional capacity examined using expanded disability status scale edss results prevalence rls 413 compared msrls group rls higher edss scores cranial spinal lesions longer disease duration older msrls+ group symptom severity scores positively correlated higher anxiety poorer sleep quality symptom severity score negatively correlated mental hrqol pain scores conclusion conclusion findings current study indicate negative impact rls functional capacity anxiety sleep quality mental hrqol ms patients studies using accurate diagnostic strategies identifying rls sleep disorders necessary clarify association ms rls explore relevant clinical implications keywords restless legs syndrome sleep disorder multiple sclerosis,0.0
evaluation neuroprotective effects alphatocopherol cuprizoneinduced demyelination model multiple sclerosis res pharm sci 2020 nov 27 15 6 602611 doi 104103 17355362301345 ecollection 2020 decabstractbackground purpose multiple sclerosis ms autoimmune disorder characterized demyelination axonal loss quantitative estimation behavioral locomotor histological changes following use alphatocopherol animal model ms reported present study planned evaluate whether can improve sensorimotor dysfunction reduce demyelination cuprizone cpz induced rat model msexperimental approach female spraguedawley rats 8 weeks fed cuprizone diet 5 weeks followed intraperitoneal injections alphatocopherol 100 mg kg pbs 2 weeks groups e1 e2 n 8 group c n 8 fed normal pellets followed intraperitoneal doses pbs openfield test beam walking carried every 10th day mean area demyelination corpus callosum quantified luxol fast blue lfb stained histological sections forebrain qualitative grading relative changes stains myelinated fibers also donefindings results withdrawal cpz treatment increased average speed 22 group e1 compared group e2 p 005 mean time walk beam reduced group e1 26 compared group e2 p 005 rearing frequency increased group e1 week 67 compared period cpz treatment mean area demyelination corpus callosum showed 12 reduction group e1 compared group e2 p 005 conclusion implications shortterm therapy showed improvement motor dysfunction reduction demyelination animal model mspmid33828603 pmcpmc8020858 doi104103 17355362301345,1.0
electronic unsupervised patientreported expanded disability status scale multiple sclerosis abstractbackgroundin persons multiple sclerosis ms expanded disability status scale edss criterion standard assessing disability inperson nature constrains patient participation research clinical assessmentsobjectivethe aim study develop validate scalable electronic unsupervised patientreported edss epredss capture msrelated disability across spectrum severitymethodswe enrolled 136 adult ms patients split preliminary testing cohort 1 n50 validation cohort 2 n86 evenly distributed across edss groups patient completed epredss either immediately ms clinicians neurostatus edss evaluationresultsin cohort 2 mean age 506years range 2680 median edss 35 interquartile range iqr 15 55 epredss edss agreed within 1point 86 examinations kappa agreement within 1point 085 p0001 correlation coefficient two measures 091 0001 discussionthe epredss highly correlated edss good agreement even lower edss levels clinical care epredss enable longitudinal monitoring patients disability research provides valid rapid measure across entire spectrum disability permits broader participation fewer inperson assessments,0.0
efficacy highintensity aerobic exercise cognitive performance people multiple sclerosis randomized controlled trial abstractbackgroundcognitive impairment highly prevalent multiple sclerosis ms progressive aerobic exercise pae represents promising approach toward preservation even improvement cognitive performance people ms pwms objectiveto investigate effects pae cognitive domains information processing learning memory verbal fluency pwmsmethodsthis randomized controlled trial included exercise n43 24weeks supervised pae followed selfguided physical activity waitlist group n43 24weeks habitual lifestyle followed supervised pae assessments included brief repeatable battery neuropsychological tests brbn selfreported mood cardiorespiratory fitness published reference data used compute zscores brbn scores cognitive impairment defined one zscores15sdresultsno betweengroup changes total group observed brbn scores following pae cognitively impaired subgroup 43 total group betweengroup point estimate suggested potential clinical relevant improvement symbol digit modalities test 95 ci overlapping zero cardiorespiratory fitness increased total group cognitively impaired subgroupconclusionin present representative ms group 24weeks supervised pae effect cognitive domain total group potentially improved processing speed cognitively impaired subgroup,0.0
ferroptosis mediates cuprizoneinduced loss oligodendrocytes demyelination multiple sclerosis ms chronic demyelinating disease cns cuprizone cz copper chelator widely used study demyelination remyelination cns context ms however mechanisms underlying oligodendrocyte ol cell loss demyelination known coppercontaining enzymes play important roles iron homeostasis controlling oxidative stress examined whether chelating copper leads disruption molecules involved iron homeostasis can trigger ironmediated ol loss show giving mice male cz diet induces rapid loss ol corpus callosum 2 d accompanied expression several markers ferroptosis relatively newly described form ironmediated cell death ferroptosis ironmediated free radicals trigger lipid peroxidation conditions glutathione insufficiency reduced capacity repair lipid damage confirmed using smallmolecule inhibitor ferroptosis prevents czinduced loss ol demyelination providing clear evidence copperiron connection czinduced neurotoxicity work wider implications disorders multiple sclerosis cns injurysignificance statement cuprizone cz copper chelator induces demyelination although widely used model study demyelination remyelination context multiple sclerosis mechanisms mediating demyelination fully understood study shows first time cz induces demyelination via ferroptosismediated rapid loss oligodendrocytes work shows chelating copper cz leads expression molecules rapidly mobilize iron ferritin iron storage protein triggers ironmediated lipid peroxidation oligodendrocyte loss via ferroptosis rapid mobilization iron cellular stores may also play role cell death neurologic conditions,1.0
hescderived immune suppressive dendritic cells induce immune tolerance parental hescderived allografts background inherent capability unlimited selfrenewal unique potential differentiate functional cells three germ layers human embryonic stem cells hescs hold great potential regenerative medicine major challenge application hescbased cell therapy allogeneic immune rejection hescderived allografts methods derived dendritic celllike cells dcls wild type ctla4ig pdl1 knockin hescs denoted wt dcls cp dcls expression dcrelated genes surface molecules evaluated well dcl capacity stimulate allogeneic t cells induce regulatory t treg cells vitro using immune system humanized mouse model investigated whether adoptive transfer cp dcls can induce longterm immune tolerance parental hescderived smooth muscle cardiomyocyte allografts findings cp dcls can maintain immune suppressive properties robust inflammatory stimulation induce treg cells cp dcls survive transiently vivo induce longterm immune tolerance parental hescderived allografts interpretation strategy cause systemic immune suppression induces immune tolerance specific dclspecific hlas thus presents safe effective approach induce immune tolerance allografts derived clinically approved hesc line funding nsfc leading talents guangdong province program 00201516 key rd program guangdong province 2019b020235003 science technology innovation committee shenzhen municipality jcyj20180504170301309 national hightech rd program 863 program 2015aa020310 shenzhen sanming project medicine szsm201602102 development reform commission shenzhen municipality s2016004730009 cirm disc210559,0.0
safety efficacy amantadine modafinil methylphenidate fatigue multiple sclerosis randomised placebocontrolled crossover doubleblind trial summarybackgroundmethylphenidate modafinil amantadine commonly prescribed medications alleviating fatigue multiple sclerosis however evidence supporting efficacy sparse conflicting goal compare efficacy three medications placebo patients multiple sclerosis fatiguemethodsin randomised placebocontrolled foursequence fourperiod crossover doubleblind trial patients multiple sclerosis reported fatigue modified fatigue impact scale mfis score 33 recruited two academic multiple sclerosis centres usa participants received oral amantadine 100 mg twice daily modafinil 100 mg twice daily methylphenidate 10 mg twice daily placebo given 6 weeks patients intended receive four study medications turn one four different sequences 2week washout periods medications biostatistician prepared concealed allocation schedule stratified site randomly assigning sequence medications approximately 1111 ratio blocks eight consecutive series numbers statistician pharmacists role assessing participants collecting data participants caregivers assessors masked allocation primary outcome measure mfis measured taking highest tolerated dose week 5 medication period analysed use linear mixedeffect regression model trial registered clinicaltrialsgov nct03185065 closedfindingsbetween oct 4 2017 feb 27 2019 169 patients screened 141 patients enrolled randomly assigned one four medication administration sequences 35 25 patients amantadine placebo modafinil methylphenidate sequence 34 24 patients placebo methylphenidate amantadine modafinil sequence 35 25 patients modafinil amantadine methylphenidate placebo sequence 37 26 patients methylphenidate modafinil placebo amantadine sequence data 136 participants available intentiontotreat analysis primary outcome estimated mean values mfis total scores baseline maximal tolerated dose follows 513 95 ci 490536 baseline 406 382431 placebo 413 388437 amantadine 390 366414 modafinil 386 362410 methylphenidate p020 overall medication effect linear mixedeffect regression model compared placebo 38 31 124 patients higher proportions participants reported adverse events taking amantadine 49 39 127 patients modafinil 50 40 125 patients methylphenidate 51 40 129 patients three serious adverse events occurred study pulmonary embolism myocarditis taking amantadine multiple sclerosis exacerbation requiring hospital admission taking modafinil interpretationamantadine modafinil methylphenidate superior placebo improving multiple sclerosis fatigue caused frequent adverse events results study support indiscriminate use amantadine modafinil methylphenidate treatment fatigue multiple sclerosisfundingpatientcentered outcomes research institute,0.0
drugs multiple sclerosis fatigue just placebos 80 multiple sclerosis patients fatigue commonly troublesome problem 1 2 fatigue often disabling affecting employment activities unfortunately multiple sclerosis fatigue difficult treat frustrating patients ourselves treatments include exercise energy conservation cognitive behavioural counselling physicians inclined prescribe medications patients multiple sclerosis fatigue patients often report medication prescribed improved fatigue however conflicting evidence whether drugs commonly prescribed multiple sclerosis fatigue effective 3 4 medications truly effective placebo effect,0.0
expansion chronic lesions linked disease progression relapsingremitting multiple sclerosis patients abstractbackgroundslowburning inflammation putatively associated lesion expansion leads progressive loss axons disability worseningobjectiveto investigate incidence extent chronic white matter lesion expansion relapsingremitting multiple sclerosis rrms patients evaluate relationship biomarkers disease progressionmethodspre postgadolinium t1 fluidattenuated inversion recovery flair diffusion tensor images acquired 33 patients lesional activity analysed baseline 48months using customdesigned softwareresultsa total 569 lesions identified chronic baseline 261 expanding 236 stable 72 shrinking addition 139 new lesions confluent freestanding observed chronic lesion expansion associated patients age accounted bulk 673 total brain lesion volume increase 327 attributable new lesion formation change chronic lesion volume correlated rate brain atrophy r057 p0001 change expanded disability status scale edss r038 p003 increase isotropic diffusivity inside lesions r075 p0001 conclusionexpansion chronic lesions rrms patients primary determinant increased t2 total lesion load significantly contributes disease progression partially driving axonal loss inside lesions brain damage outside lesional tissue,0.0
ozanimod treatment relapsingremitting multiple sclerosis adults systematic review metaanalysis randomized controlled trials front pharmacol 2020 nov 20 11589146 doi 103389 fphar2020589146 ecollection 2020abstractbackground ozanimod approved use treatment relapsing forms multiple sclerosis united states fda novel orally available sphingosine 1phosphate receptor modulator ozanimod selectively binds s1p1 s1p5 receptor high affinity minimizing safety concerns caused s1p3 receptor activation methods e systematically searched pubmed embase database cochrane library database identify randomized controlled trials rcts inception june 28 2020 trials considered eligible 1 randomized clinical trials rcts 2 enrolled adult participants diagnosed relapsingremitting ms 3 compared ozanimod placebo approved dmds evaluated phase iii phase ii clinical trials 4 enrolled 100 participants 5 provided available information predefined primary secondary outcomes results 2917 participants three highquality multicentered randomized clinical trials pooled analysis found using ozanimod significantly associated reduction annualized relapse rate treatment period rr 010 95 ci 015 006 also decreased number gadoliniumenhancing lesions end trial relative treatment ozanimod ozanimod 029 control 065 rr 020 95 ci 034 006 compared patients control group number new enlarging t2 lesions treatment period decreased patients treated ozanimod ozanimod 182 control 355 rr 112 95 ci 152 071 safety endpoints patients ozanimod group reported lower rate adverse events ozanimod 6603 control 7707 rr 064 95 ci 043 095 similar incidence infectionrelated teaes found across treatment groups nasopharyngitis ozanimod 1119 control 983 rr 110 95 ci 077157 urinarytract infection ozanimod 381 control 297 rr 129 95 ci 083200 case macular edema noted well seconddegree type 2 thirddegree atrioventricular block subgroup analysis compared 05 mg ozanimod 1 mg ozanimod related significant reduction annualized relapse rate treatment period 1 mg ozanimod 018 05 mg ozanimod 024 rr 005 95 ci 001 009 decreased number new enlarging t2 lesions treatment period 1 mg ozanimod 158 05 mg ozanimod 205 rr 049 95 ci 019 079 significant difference causing adverse events 1 05 mg found conclusions metaanalysis found favorable safety performance use ozanimod treatment relapsingremitting multiple sclerosis adults associated significant reduction annualized relapse rate treatment period decreased number gadoliniumenhancing lesions end trial lowered number new enlarging t2 lesions treatment period ozanimod 1 mg outperformed 05 mg dose efficacy without increasing risk adverse eventspmid33658933 pmcpmc7919188 doi103389 fphar2020589146,0.0
siponimod disentangling disability relapses secondary progressive multiple sclerosis abstractbackgroundin multiple sclerosis impact treatment disability progression can confounded treatment also reduces relapsesobjectiveto distinguish siponimods direct effects disability progression relapses expand phase 3 trialmethodsthree estimands one based principal stratum two hypothetical scenarios relapses equal relapses treatment arms defined determine extent siponimods effects 3 6month confirmed disability progression independent onstudy relapsesresultsprincipal stratum analysis estimated siponimod reduced risk 3 6month confirmed disability progression 1420 2933 respectively compared placebo nonrelapsing patients hypothetical scenarios risk reductions independent relapses 1418 23 3 6month confirmed disability progression respectivelyconclusionby controlling confounding impact onstudy relapses confirmed disability progression statistical approaches provide methodological framework assess treatment effects disability progression relapsing nonrelapsing patients analyses support siponimod may useful treating secondary progressive multiple sclerosis patients without relapses,0.0
depression cognitive function early multiple sclerosis multitasking sensitive traditional assessments abstractbackgroundpersons multiple sclerosis ms depression symptoms report realworld cognitive difficulties may missed laboratory cognitive testsobjectiveto examine relationship depressive symptoms cognitive monotasking versus multitasking early msmethodpersons early ms n185 5years diagnosed reported mood completed monotasking multitasking cognitive tests received highresolution 30t magnetic resonance imaging mri partial correlations analyzed associations mood cognition controlling age sex estimated premorbid iq t2 lesion volume normalized gray matter volumeresultsdepression symptoms related worse cognitive multitasking 0353 p0001 monotasking r0189 p0011 significant albeit weaker link cognitive efficiency composite score r0281 p0001 composite memory r0036 p050 findings replicated second depression measure multitasking worse patients least mild depression patients minimal depression healthy controls multitasking related mood healthy controlsconclusionsdepression symptoms linked cognitive multitasking early ms standard monotasking cognitive assessments appear less sensitive depressionrelated cognition investigation determine directionality mechanisms relationship goal enhancing treatment cognitive dysfunction depression ms,0.0
decreased levels interleukin 27 serum vitiligo patients background vitiligo common skin disorder melanocytes destroyed autoreactive immune responses loss melanocytes results appearance depigmented areas different parts body cytokines remarkable roles pathogenesis vitiligo il1 il6 tnf interleukin 27 il27 new member il6 il12 family mainly released activated antigenpresenting cells il27 suggested function proinflammatory well antiinflammatory cytokine altered concentrations il27 shown various autoimmune diseases multiple sclerosis rheumatoid arthritis psoriasis studies conducted determine expression cytokine vitiligo patients objective objective study determine serum concentration il27 vitiligo patients compare normal individuals methods serum concentration il27 79 vitiligo patients evaluated comparison 45 healthy controls using elisa assay results results showed decreased concentration il27 vitiligo patients compared healthy subjects p 0026 furthermore correlation il27 concentrations disease parameters vitiligo severity extension depigmented area observed study limitation larger sample size recommended study conclusion reduction serum levels il27 vitiligo patients compared normal subjects suggested possible antiinflammatory role cytokine vitiligo thus il27 may considered new target manipulation immune system vitiligo patients,0.0
occurrence microstructural features slowly expanding lesions fingolimod natalizumab treatment multiple sclerosis abstractbackgroundin multiple sclerosis ms 57 white matter lesions chronically active slowly expanding lesions sels contribute disability progressionobjectivethe aim study compare fingolimod natalizumab effects progressive linearly enlarging lesions ie sels putative biomarker smouldering inflammationmethodsrelapsingremitting ms patients starting fingolimod n24 natalizumab n28 underwent 3t brain magnetic resonance imaging mri baseline months 6 12 24 sels identified among baselinevisible lesions showing125 annual increase calculated linearly fitting jacobian nonlinear deformation field timepoints obtained combining t1 t2weighted scans sel burden magnetization transfer ratio mtr t1 signal intensity compared using linear modelsresultsthe prevalences fingolimod 75 natalizumab patients 46 with1 sel significantly different adjustedp008 fingolimod group higher sel number volume adjustedp0047 false discovery rate fdr survived groups sels versus nonsels showed lower mtr t1 signal intensity adjustedp001 fdrsurvived longitudinally nonsel mtr increased treatment groups adjustedp0005 fdrsurvived t1 signal intensity decreased sels treatments adjustedp0049 fdrsurvived fingolimod group increased natalizumab nonsels adjustedp003 fdrsurvived conclusionthe effects natalizumab fingolimod sel occurrence seem modest natalizumab slightly effective treatments may promote reparative mechanisms stable chronic inactive lesions,0.0
effectiveness percutaneous posterior tibial nerve stimulation management bowel dysfunction multiple sclerosis patients abstractbackgroundneurogenic bowel dysfunctions nbds form fecal incontinence fi functional constipation fc frequent multiple sclerosis ms patients significantly affect quality life therapeutic options limitedobjectiveto investigate effectiveness percutaneous posterior tibial nerve stimulation ptns ms patients suffering fi fcmethodsprevalence severity fi fc prospectively collected among ms patients undergoing 12weeks ptns neurogenic bladder cleveland clinic fecal incontinence score ccfis rome iii criteria used define fi fc respectively subjective treatment satisfaction estimated using benefit satisfaction willingness continue bswc questionnaireresultsa total 60 patients undergoing ptns suffered nbds 25 fi+ fc+ 5 fi+ fc 30 fi fc+ median ccfis decreased ptns 120 110130 85 70110 p0001 particular improvements liquid flatal incontinence pads need lifestyle restrictions seven patients became fc free ptns patients developed fc study p0023 50 patients satisfied willing continue ptns study endconclusionptns represents valid minimally invasive alternative treatment ms patients suffering nbds,0.0
effect tonsillectomy john cunningham virus serological status multiple sclerosis patients retrospective casecontrol study abstracttonsils believed initial site john cunningham virus jcv infection longterm effect childhood tonsillectomy jcv status multiple sclerosis ms patients investigated retrospective casecontrol study analyzed data 144 jcv seropositive cases 82 jcv seronegative controls three outpatient ms clinics united states early tonsillectomy age 8 reported among 8 556 jcv seropositive subjects 19 2317 controls early tonsillectomy associated jcv negative status adjusted odds ratio 539 95 confidence interval 2131362 p0001 independent age gender,0.0
cotinine measure smoking observational studies multiple sclerosis abstractstudies using cotinine levels define smokers generally failed detect association smoking multiple sclerosis ms using swedish populationbased casecontrol study show associations relation ms risk progression differ considerably depending smoking measured risk conversion secondary progressive disease increased among smokers selfreported smoking history presumed cotinine levels used define smokers defining smoking cotinine levels without distinguishing different sources nicotine may lead severely biased estimates association smoking ms risk progression,0.0
high antijcpyv serum titers coincide high csf cell counts rrms patients abstractbackgroundprogressive multifocal leukoencephalopathy pml can rare cases occur natalizumabtreated patients high serum antijcpyv antibodies hypothetically due excessive blockade immune cell migrationobjectiveimmune cell recruitment central nervous system cns assessed relapsingremitting multiple sclerosis rrms patients stratified low versus high antijcpyv antibody titers indicator pml riskmethodscerebrospinal fluid csf cell counts 145 rrms patients quantified flow cytometry generalized linear models employed assess influence age sex disease duration expanded disability status scale edss clinical radiological activity current steroid natalizumab treatment well antijcpyv serology csf cell subset countsresultswhile clinical radiological activity associated increased cd4 natural killer nk b plasma cell counts natalizumab therapy reduced subpopulations except monocytes without natalizumab therapy patients high antijcpyv serum titers presented increased csf tcell counts compared patients low antijcpyv serum titers contrast pml patients assessed n2 diagnosis n5 presented comparably low cd8 bcell counts increased plasma exchange n4 conclusionhigh antijcpyv indices indicative increased viral activity associated elevated immune cell recruitment cns excessive impairment conjunction viral activity predispose pml development,0.0
realworld keystroke dynamics potentially valid biomarker clinical disability multiple sclerosis abstractbackgroundclinical measures multiple sclerosis ms face limitations may overcome utilising smartphone keyboard interactions acquired continuously remotely regular typingobjectivethe aim study determine reliability validity keystroke dynamics assess clinical aspects msmethodsin total 102 ms patients 24 controls included observational study keyboard interactions obtained neurokeys keyboard app eight timingrelated keystroke features assessed reliability intraclass correlation coefficients iccs construct validity analysing group differences fatigue gadoliniumenhancing lesions magnetic resonance imaging mri patients vs controls concurrent validity correlating disability measuresresultsreliability moderate two icc0601 0742 good excellent remaining six features icc07600965 patients significantly higher keystroke latencies controls latency key presses correlated highest expanded disability status scale r0407 latency key releases ninehole peg test symbol digit modalities test 0503 r0553 respectively ps0001conclusionkeystroke dynamics reliable distinguished patients controls associated clinical disability measures consequently keystroke dynamics promising valid surrogate marker clinical disability ms,0.0
cxcl13 cxcr5 signalling pivotal preserve motor neurons amyotrophic lateral sclerosis abstractbackgroundcxcl13 b t lymphocyte chemokine mediates neuroinflammation receptor cxcr5 chemokine highly expressed motoneurons mns amyotrophic lateral sclerosis als sod1g93a msod1 mice disease particularly fastprogressing mice accordingly study investigated role chemokine alsmethodswe used vitro vivo experimental paradigms derived als mice patients investigate expression level distribution cxcl13 cxcr5 axis role mn death disease progression moreover compared levels cxcl13 csf serum als patients controlsfindingscxcl13 cxcr5 overexpressed spinal mns peripheral axons msod1 mice cxcl13 inhibition cns als mice resulted exacerbation motor impairment n4 group mean_diff2781 decrease survival n14_treated192105wks n17_controls20206wks 95 ci 046871929 corroborated evidence primary spinal cultures inhibition activation cxcl13 exacerbated prevented mn loss besides found cxcl13 cxcr5 axis overexpressed spinal cord mns als patients cxcl13 levels csf discriminate als n30 multiple sclerosis n16 patients sensitivity 9756interpretationwe hypothesise mns activate cxcl13 signalling attenuate cns inflammation prevent neuromuscular denervation low levels cxcl13 csf als patients might reflect mn dysfunction suggesting chemokine potential clinical adjunct discriminate als neurological diseasesfundingvaccinex inc regione lombardia transals,0.0
selfreported cognitive impairment individuals primary immunodeficiency disease brain behav immun health 2020 nov 5 9100170 doi 101016 jbbih2020100170 ecollection 2020 decabstractindividuals primary immunodeficiency disease pid increased risk infection autoimmune conditions inflammatory disorders cognitive impairment also referred brain fog recognized medical conditions sideeffect treatments however previously reported individuals pid phenomenon brain fog recognized autoimmune inflammatory conditions including lupus multiple sclerosis chronic fatigue syndrome resulted chemotherapy treatment cancer research investigates selfreported memory function individuals diagnosis pid respondents completed survey used reliable valid questionnaires memory functioning questionnaire becks depression inventory ii becks anxiety inventory 292 completed surveys 133 report comorbid neurological diagnosis incident concussion influence perceived memory function compared normative scores respondents study found significantly greater perceived memory impairment respondents significant higher score anxiety depression compared nonanxious nondepressed normative values study finds individuals diagnosis pid greater degree perceived memory impairment brain fog addition greater levels anxiety depression individuals diagnosis pid benefit prospective surveillance comprehensive neuropsychological assessment track cognitive status implement corrective measures decline identifiedpmid34589905 pmcpmc8474660 doi101016 jbbih2020100170,0.0
bestms prospective headtohead comparative study natalizumab fingolimod active relapsing ms abstractbackgroundthere headtohead studies compare highly active treatments multiple sclerosis ms objectivethe aim study compare effectiveness natalizumab ntz fingolimod fty active relapsingremitting msmethodbest escalation strategy multiple sclerosis bestms multicentric prospective study 12month followup including patients active ms treatment choice discretion physician clinical magnetic resonance imaging mri data collected baseline 12months primary outcome proportion patients reaching evidence disease activity neda 12months secondary outcomes included annualized relapse rate mri activityresultsa total 223 patients included ntz 109 fty 114 treatment groups well balanced baseline proportion neda patients 478 ntz group versus 304 fty group p0015 superiority driven annualized relapse rate mri activity multivariate analysis treatment group factor associated neda 12months lower probability fty group odds ratio 049 p0029 conclusionbestms prospective study compared headtohead effectiveness ntz fty active relapsingremitting ms results suggest superiority ntz fty,0.0
longterm followup oratorio trial ocrelizumab primary progressive multiple sclerosis posthoc analysis ongoing openlabel extension randomised placebocontrolled phase 3 trial summarybackgroundthe safety efficacy ocrelizumab primary progressive multiple sclerosis shown phase 3 oratorio trial study assessed effects maintaining switching ocrelizumab therapy measures disease progression safety openlabel extension phase oratoriomethodsoratorio international multicentre doubleblind randomised placebocontrolled phase 3 trial done 182 study locations including academic centres hospitals community speciality centres within 29 countries across americas australia europe israel new zealand russia patients primary progressive multiple sclerosis aged 1855 years expanded disability status scale edss score 3065 eligible enrolment previous treatment bcelltargeted therapies immunosuppressive medications excluded eligible participants randomly assigned 21 receive either intravenous infusion 600 mg ocrelizumab two 300 mg infusions 14 days apart placebo every 24 weeks least 120 weeks prespecified number n253 disability events occurred doubleblind phase patients entered extended controlled period variable duration investigators became aware treatment allocation following period patients enter optional openlabel extension continued ocrelizumab switched placebo ocrelizumab time onset disability progression confirmed 24 weeks four measures ie increase edss score 20 increase time complete 9hole peg test 9hpt 20 increase time perform timed 25foot walk t25fw composite progression defined first confirmed occurrence three individual measures time requiring wheelchair edss 7 conventional mri measures also analysed intentiontotreat population used safety efficacy analyses analyses timings done post hoc oratorio registered clinicaltrialsgov nct01194570 ongoingfindingsfrom march 3 2011 dec 27 2012 488 patients randomly assigned ocrelizumab group 244 placebo group extended controlled period started july 24 2015 ended april 27 2016 last patient entered openlabel extension overall 544 74 732 participants completed doubleblind period week 144 527 97 544 entered openlabel extension phase 451 86 ongoing openlabel extension least 65 study years 48 weeks per study year followup proportion patients progression disability measures lower initiated ocrelizumab early initially receiving placebo measures 24week confirmed disability progression edss 517 vs 648 difference 131 95 ci 49213 p00018 9hpt 306 vs 431 125 41209 p00035 t25fw 632 vs 707 75 03 152 p0058 composite progression 732 vs 833 101 36166 p00023 confirmed time requiring wheelchair 115 vs 189 74 08139 p00274 study end percentage change baseline lower initiated ocrelizumab early initially receiving placebo t2 lesion volume 045 vs 1300 p00001 t1 hypointense lesion volume 3668 vs 6093 p00001 entire period oratorio ocrelizumab exposure population rate adverse events 23809 95 ci 2327124357 per 100 patientyears serious adverse events 1263 95 ci 11411394 per 100 patientyears common serious adverse events infections 413 95 ci 345491 per 100 patientyears new safety signals emerged compared doubleblind phase oratoriointerpretationcompared patients switching placebo earlier continuous ocrelizumab treatment provided sustained benefits measures disease progression 65 study years followup although study shows benefit earlier intervention ocrelizumab primary progressive disease progression remains important unmet need multiple sclerosis research focus potential benefits described study might improved upon particularly longer time periodsfundingf hoffmannla roche,0.0
longterm ocrelizumab progressive multiple sclerosis pathophysiology progressive multiple sclerosis includes acute inflammatory lesion activity chronic inflammation neurodegeneration 1 exact relationship components remains unclear despite success development diseasemodifying therapies relapsingremitting multiple sclerosis treatment progressive multiple sclerosis proven difficult primary progressive multiple sclerosis characterised gradual disability accumulation disease onset sometimes superimposed relapses mri lesion activity 1 currently anticd20 monoclonal antibody ocrelizumab diseasemodifying therapy approved treat primary progressive multiple sclerosis evidence ocrelizumab based results oratorio phase 3 trial 2 treatment intravenous 600 mg ocrelizumab every 6 months reduced 3monthconfirmed worsening expanded disability status scale edss score compared placebo primary results supported benefit 6monthconfirmed worsening edss score timed 25foot walk t25fw another measure neurological disability mri lesion activity whole brain volume loss,0.0
agingexacerbated acute axon myelin injury associated microgliaderived reactive oxygen species alleviated generic medication indapamide age critical risk factor many neurologic conditions including progressive multiple sclerosis yet mechanisms underlying relationship unknown using lysolecithininduced demyelinating injury mouse spinal cord characterized acute lesion investigated mechanisms increased myelin axon damage age report exacerbated myelin axon loss middleaged 810 months age compared young 6 weeks age female c57bl 6 mice 13 d lesion evolution white matter transcriptomic analysis linked elevated injury increased expression cybb gene encoding catalytic subunit nadph oxidase gp91phox immunohistochemistry male female cx3cr1creer +rosa26tdtom + mice gp91phox revealed upregulation middleaged animals occurred primarily microglia infiltrated monocytederived macrophages activated nadph oxidase generates reactive oxygen species elevated oxidative damage corroborated higher malondialdehyde immunoreactivity lesions middleaged compared young mice previously conducted screen generic drugs antioxidant properties selected antihypertensive cnspenetrant medication indapamide investigation report indapamide reduced superoxide derived microglia cultures treatment middleaged mice indapamide associated decrease ageexacerbated lipid peroxidation demyelination axon loss summary ageexacerbated acute injury following lysolecithin administration mediated part microglia nadph oxidase activation alleviated cnspenetrant antioxidant indapamidesignificance statement age associated increased risk development several neurologic conditions including progressive multiple sclerosis represented substantial microglia activation demonstrate lysolecithin demyelination model young middleaged mice latter group developed greater acute axonal myelin loss attributed elevated oxidative stress nadph oxidase lineagetraced microglia thus used cnspenetrant generic medication used hypertension indapamide found antioxidant properties previous drug screen following lysolecithin demyelination middleaged mice indapamide treatment associated decreased oxidative stress axon myelin loss propose indapamide potential adjunctive therapy agingassociated neurodegenerative conditions alzheimer9s disease progressive multiple sclerosis,1.0
longterm prognostic counselling people multiple sclerosis using online analytical processing tool abstractbackgroundprognostic counselling sensitive issue medicine especially ms due highly heterogeneous disease course however people ms pwms seek prognostic information webbased evidencebased decision support tool multiple sclerosis ebdims uses data 717 patients london ontario cohort calculate personalized longterm prognostic informationobjectivethe aim study investigate feasibility effect longterm prognostic counselling pwms using ebdimsmethodsninety consecutive pwms provided personalized estimations expected time reach expanded disability status scale edss scores 6 8 time conversion secondaryprogressive ms participants gave estimates putative prognosis rated tools acceptability sixstep likerttype scalesresultsparticipants rated ebdims highly understandable interesting relevant patientphysician encounters coping therapy decisions although provoked certain degree worry participants 95 recommend using tool participants prognosis estimates change significantly following ebdimsconclusionlongterm prognostic counselling using online tool shown feasible clinical setting ebdims provides pwms relevant easytounderstand longterm prognostic information without causing relevant anxiety,0.0
increased functional sensorimotor network efficiency relates disability multiple sclerosis abstractbackgroundnetwork abnormalities help explain physical disability multiple sclerosis ms remains poorly understoodobjectivethis study investigates functional network efficiency changes sensorimotor systemmethodswe included 222 ms patients divided low disability ld expanded disability status scale edss 35 n185 high disability hd edss 6 n37 82 healthy controls hc functional connectivity assessed 23 sensorimotor regions measures efficiency computed compared groups using general linear models corrected age sex binary logistic regression models related disability status local functional network efficiency le brain volumes demographics functional connectivity patterns regions important disability exploredresultshd patients demonstrated significantly higher le left primary somatosensory cortex s1 right pallidum compared ld hc left premotor cortex compared hc logistic regression model disability r2038 included age deep grey matter volume left s1 le s1 functional connectivity increased prefrontal secondary sensory areas hd patients compared ld hcconclusionclinical disability ms associates functional sensorimotor increases efficiency connectivity centred around s1 independent structural damage,0.0
agerelated adverse events diseasemodifying treatments multiple sclerosis metaregression abstractobjectiveto verify hypothesis agedependent increase infections neoplasms patients multiple sclerosis ms diseasemodifying treatments dmts different mechanisms actionmethodswe extracted relevant data 45 randomized clinical trials rcts currently licensed dmts fitted inversevariance weighted metaregressions randomeffects models estimate whether age mechanism action immunomodulatory sequestrating depletive currently licensed dmts influenced difference experimental arm control arm incidence specific adverse events namely overall infections opportunistic infections neoplasmsresultsa higher incidence overall infections observed rcts depletive dmts eventrate ratio125 p0001 herpetic infections frequently observed rcts depletive eventrate ratio351 p0001 lesser extent sequestrating dmts eventrate ratio152 p0078 interaction age depletive dmts associated higher incidence neoplasms p0017 especially 45years agediscussionour study supports detrimental effect age safety profile depletive dmts increased incidence neoplasms especially 45years age failed demonstrate agerelated increased incidence infections possibly due latency occurrence,0.0
depression anxiety patients multiple sclerosis treated interferonbeta fingolimod role indoleamine 2 3dioxygenase proinflammatory cytokines brain behav immun health 2020 oct 23 9100162 doi 101016 jbbih2020100162 ecollection 2020 decabstractdepression anxiety d occurs 50 multiple sclerosis ms patients proinflammatory cytokines induce classical symptoms depression activation inflammatory response also triggers production indoleamine 2 3dioxygenase ido catabolizes tryptophan amino acid precursor serotonin melatonin suggested ido link immune serotonergic systems study aimed quantify levels ido proinflammatory antiinflammatory cytokines patients ms depression according treatment interferonbeta ifn fingolimod study inclusion criteria age 1860 years clinical radiological diagnosis ms one hundred thirtytwo patients diagnosed mcdonalds criteria followed braslia district hospital brazil relapsingremitting ms identified potential study participants thirtyfive patients identified receiving treatment fingolimod ifn diagnosis d ido proinflammatory antiinflammatory cytokine levels compared 35 patients 18 healthy controls level il10 antiinflammatory cytokine lower fingolimodtreated p 0001 ifntreated p 001 patient groups control group ifntreated patients showed increased ido expression decreased inflammatory cytokine levels contrast fingolimodtreated patients showed significantly decreased expression ido significantly increased levels proinflammatory cytokines produced innate immune cells including tumor necrosis factoralpha interleukin6 agents used treat ms maintain symptoms d patients ms via different mechanismspmid34589900 pmcpmc8474597 doi101016 jbbih2020100162,0.0
highdose biotin multiple sclerosis end road since first pilot study highdose biotin patients chronic progressive multiple sclerosis 1 subsequent phase 2 randomised doubleblind placebocontrolled trial msspi 2 biotin discussed potentially unique approach treat progressive multiple sclerosis targeting remyelination biotin cofactor four essential carboxylases might support myelin repair enhancing fatty acid synthesis protect hypoxiadriven axonal degeneration augmenting energy production neurons 1 3,1.0
safety efficacy md1003 highdose biotin patients progressive multiple sclerosis spi2 randomised doubleblind placebocontrolled phase 3 trial summarybackgroundthere unmet need develop therapeutic interventions directed neurodegeneration underlies progression multiple sclerosis highdose pharmaceuticalgrade biotin md1003 might enhance neuronal oligodendrocyte energetics resulting improved cell function repair survival msspi randomised doubleblind placebocontrolled study found md1003 improved disability outcomes 12 months patients progressive multiple sclerosis spi2 study designed assess safety efficacy md1003 progressive forms multiple sclerosis larger representative patient cohortmethodsspi2 randomised doubleblind parallelgroup placebocontrolled trial done 90 academic community multiple sclerosis clinics across 13 countries patients aged 1865 years diagnosis primary secondary progressive multiple sclerosis fulfilling revised international panel criteria lublin criteria kurtzke pyramidal functional subscore least 2 defined minimal disability expanded disability status scale edss score 3565 timed 25foot walk tw25 less 40 s evidence clinical disability progression relapses 2 years enrolment concomitant diseasemodifying therapies allowed patients randomly assigned 11 independent statistician using interactive web response system stratification study site disease history receive md1003 oral biotin 100 mg three times daily placebo participants investigators assessors masked treatment assignment primary endpoint composite proportion participants confirmed improvement edss tw25 month 12 confirmed month 15 versus baseline primary endpoint assessed intentiontotreat analysis set participants completed month 15 visit safety analyses included participants received least one dose md1003 trial registered clinicaltrialsgov nct02936037 eudract database 201600070029 findingsfrom feb 22 2017 june 8 2018 642 participants randomly assigned md1003 n326 placebo n316 doubleblind placebocontrolled phase study ended primary endpoint lastentered participant assessed nov 15 2019 mean time placebocontrolled phase 201 months sd 53 range 1527 primary outcome 39 12 326 patients md1003 group compared 29 9 316 placebo group improved month 12 confirmation month 15 odds ratio 135 95 ci 081226 treatmentemergent adverse events occurred 277 84 331 participants md1003 group 264 85 311 placebo group 87 26 331 participants md1003 group 82 26 311 participants placebo group least one serious treatmentemergent adverse event one 1 person died md1003 group deaths placebo group despite use mitigation strategies md1003 led inaccurate laboratory results tests using biotinylated antibodiesinterpretationthis study showed md1003 significantly improve disability walking speed patients progressive multiple sclerosis thus addition potential md1003 deleterious health consequences interference laboratory tests md1003 recommended treatment progressive multiple sclerosisfundingmedday pharmaceuticals,0.0
comparison neurofilament light chain results two independent facilities bmj neurol open 2020 oct 19 2 2 e000063 doi 101136 bmjno2020000063 ecollection 2020abstractobjectives examine levels neurofilament light chain nfl identical cerebrospinal fluid csf blood samples two different facilities differences affect interpretation levels within normal rangemethods csf plasma patients multiple sclerosis ms healthy controls hcs analysed simoa quanterix levels nfl providing total 165 csf samples 119 ms 225 plasma samples 180 ms results csf plasma concentrations highly correlated nfl laboratory facilities r 092 084 00001 respectively differences facilities bias two sites plasma 095 pg ml csf 7353 pg ml cutoffs csf 8075 5710 pg ml site 1 site 2 respectively cutoffs plasma 130 118 pg ml respectively seven 180 plasma samples 39 3 119 csf samples 25 ms patients reclassified normal abnormal cutoff measured different facilitiesconclusion study demonstrates results nfl csf blood measured simoa comparable facilities nevertheless healthcare practitioners consider reference values different laboratories since different sensitivity specificity can affect interpretation low values adjacent cutoffspmid33681796 pmcpmc7871722 doi101136 bmjno2020000063,0.0
brain structural functional alterations mog antibody disease abstractbackgroundthe impact myelin oligodendrocyte glycoprotein antibody disease mogad brain structure function unknownobjectivesthe aim study study multimodal brain mri alterations mogad investigate clinical significancemethodsa total 17 mogad 20 aquaporin4 antibody seropositive neuromyelitis optica spectrum disorders aqp4+nmosd 28 healthy controls hc prospectively recruited voxelwise gray matter gm volume fractional anisotropy fa mean diffusivity md degree centrality dc compared groups clinical associations differential diagnosis determined using partial correlation stepwise logistic regressionresultsin comparison hc mogad gm atrophy frontal temporal lobe insula thalamus hippocampus wm fiber disruption optic radiation anterior posterior corona radiata dc decreased cerebellum increased temporal lobe compared aqp4+nmosd mogad presented lower gm volume postcentral gyrus decreased dc cerebellum hippocampus parahippocampus atrophy associated expanded disability status scale r 055 p004 california verbal learning test r062 p0031 differentiation mogad aqp4+nmosd achieved accuracy 95 using fa splenium corpus callosum dc occipital gyrusconclusiondistinct structural functional alterations identified mogad hippocampus parahippocampus atrophy associated clinical disability cognitive impairment,1.0
ensemble learning predicts multiple sclerosis disease course summit study npj digit med 2020 oct 16 3 1 135 doi 101038 s41746020003388abstractthe rate disability accumulation varies across multiple sclerosis ms patients machine learning techniques may offer powerful means predict disease course ms patients study 724 patients comprehensive longitudinal investigation ms brigham womens hospital climb study 400 patients epic dataset university california san francisco included analysis primary outcome increase expanded disability status scale edss 15 worsening nonworsening 5 years baseline visit classification models built using climb dataset patients clinical mri longitudinal observations first 2 years validated using epic dataset compared performance three popular machine learning algorithms svm logistic regression random forest three ensemble learning approaches xgboost lightgbm metalearner l threshold established tradeoff performance two classes predictive features identified compared among different models machine learning models achieved 079 083 auc scores climb epic datasets respectively shortly disease onset ensemble learning methods effective robust compared standalone algorithms two ensemble models xgboost lightgbm superior four models evaluated study variables evaluated edss pyramidal function ambulatory index top common predictors forecasting ms disease course machine learning techniques particular ensemble methods offer increased accuracy prediction ms disease coursepmid33737720 doi101038 s41746020003388,0.0
optical coherence tomography outcomes sprintms multicenter randomized doubleblind trial ibudilast progressive multiple sclerosis abstractbackgroundthe sprintms trial demonstrated benefit ibudilast brain atrophy 96weeks progressive multiple sclerosis ms optical coherence tomography oct performed trial participantsobjectivereport oct results sprintms trialmethodsoct obtained baseline every 6months using spectral domain oct analyzed oct reading center change oct outcome measure treatment group estimated using linear mixed modelsresultschange prnfl thickness +00424um year 95 confidence interval ci 03091 03939 ibudilast versus 02630um 95 ci 05973 00714 placebo n244 p022 macular volume change 000503mm3 year 002693 001688 ibudilast versus 003659mm3 year 005824 001494 placebo spectralis cohort n61 p0044 cirrus cohort macular volume change 000040mm3 year 002167 0020866 ibudilast compared 002083mm3 year 004134 000033 placebo n183 p01734 ganglion cellinner plexiform layer thickness change available cirrus 04893um year 09132 00654 ibudilast versus 09587um year 13677 05498 placebo n183 p012 conclusionretinal thinning ms may attenuated ibudilast sample size estimates suggest oct can viable outcome measure progressive ms trials therapy large treatment effecttrial registrationnn102 sprintms clinicaltrialsgov number nct01982942,0.0
prf1 mutation alters immune system activation inflammation risk autoimmunity abstractbackgrounddefective alleles within prf1 gene encoding poreforming protein perforin combination environmental factors cause familial type 2 hemophagocytic lymphohistiocytosis fhl2 rare severe autosomal recessive childhood disorder characterized massive release cytokinescytokine stormobjectivethe aim study determine function hypomorph prf1pa91v g72360387 ga multiple sclerosis ms type 1 diabetes t1d methodswe crosscompare association data prf1pa91v mutation derived gwas adult ms pediatric t1d sardinians novel association t1d replicated metanalysis 12 584 cases 17 692 controls sardinia united kingdom scotland dissect mutation function searched coincident association immunophenotypes additional set general population sardiniansresultswe report prf1pa91v associated increase lymphocyte levels especially within cytotoxic memory tcells general population level reduced interleukin 7 receptor expression cells minor allele increased risk ms 2903 cases 2880 controls sardinia p206104 odds ratio or129 replicating previous finding whereas protects t1d p104105 or082conclusionour results indicate opposing contributions cytotoxic tcell compartment ms t1d pathogenesis,0.0
posture second strategy predicts disability progression multiple sclerosis abstractwe assessed 168 patients multiple sclerosis ms force platform obtain dualtask cost dtc balance change postural sway quiet standing dualtask condition stroop test median followup time 35years assessment disability progression occurred 45 27 patients disability progression predicted adoption posture second strategy values dtc balance exceeding obtained 62 healthy controls even controlling demographic clinical characteristics dtc balance may potentially represent novel easy tool predict ms progression,0.0
effect mood anxiety disorders health care utilization multiple sclerosis abstractbackgroundlittle known effects changes presence absence psychiatric disorders health care utilization multiple sclerosis ms objectiveto evaluate association active mood anxiety disorders mad health care utilization msmethodsusing administrative data manitoba canada identified 4748 persons ms 24 154 persons without ms matched sex birth year region using multivariable general linear models evaluated withinperson betweenperson effects active mad annual physician visits hospital days number drug classes dispensed following yearresultsannually ms cohort additional two physician visits two drug classes nearly two hospital days versus matched cohort individuals mad physician visits hospital days used drug classes individuals without mad within individuals active mad associated utilization outcomes active mad magnitude effect much smaller visits drugs betweenperson effectconclusionwithin individuals ms changes mad activity associated changes health services use,0.0
imperfect storm interleukin33 achilles heel covid19 summarythe unique cytokine signature covid19 might provide clues disease mechanisms possible future therapies propose pathogenic model alarmin cytokine interleukin il 33 key player driving stages covid19 disease ie asymptomatic mildmoderate severecritical chronicfibrotic susceptible individuals il33 release damaged lower respiratory cells might induce dysregulated gatabinding factor 3expressing regulatory t cells thereby breaking immune tolerance eliciting severe acute respiratory syndrome coronavirus 2induced autoinflammatory lung disease disease might initially sustained il33differentiated type2 innate lymphoid cells locally expanded t cells severe covid19 cases il33st2 axis might act expand number pathogenic granulocytemacrophage colonystimulating factorexpressing t cells dampen antiviral interferon responses elicit hyperinflammation favour thromboses patients survive severe covid19 il33 might drive pulmonary fibrosis inducing myofibroblasts epithelialmesenchymal transition discuss therapeutic implications hypothetical pathways including use therapies target il33 eg antist2 t helper 17like t cells immune cell homing cytokine balance,0.0
corticocortical thalamocortical changes functional connectivity white matter structural integrity rewardguided learning visuospatial discriminations rhesus monkeys frontal cortex temporal lobes together regulate complex learning memory capabilities collected restingstate functional diffusionweighted mri data male rhesus macaque monkeys received extensive training learn novel visuospatial discriminations rewardguided learning found functional connectivity changes orbitofrontal ventromedial prefrontal inferotemporal entorhinal retrosplenial anterior cingulate cortices subicular complex dorsal medial thalamus corticocortical thalamocortical changes functional connectivity accompanied related white matter structural alterations uncinate fasciculus fornix ventral prefrontal tract tracts connect sub cortical networks implicated learning memory processes monkeys humans welltrained monkeys received fornix transection impaired learning new visuospatial discriminations addition functional connectivity profile observed training altered changes accompanied white matter changes ventral prefrontal tract although integrity uncinate fasciculus remained unchanged experiments highlight importance different communication relayed among corticocortical thalamocortical circuitry ability learn new visuospatial associations learningtolearn make rewardguided decisionssignificance statement frontal neural networks temporal lobes contribute rewardguided learning mammals provide novel insight showing specific corticocortical thalamocortical functional connectivity altered rhesus monkeys received extensive training learn novel visuospatial discriminations contiguous white matter fiber pathways linking gray matter structures namely uncinate fasciculus fornix ventral prefrontal tract showed structural changes completing training visuospatial task additionally different patterns functional structural connectivity reported removal subcortical connections within extended hippocampal system via fornix transection results highlight importance corticocortical thalamocortical interactions rewardguided learning normal brain identify brain structures important memory capabilities injury,0.0
late onset macular oedema patient multiple sclerosis treated fingolimod neuroophthalmology 2020 oct 6 45 1 6164 doi 101080 0165810720201821065 ecollection 2021abstractmacular oedema rare complication fingolimod treatment usually presents within 34 months occasionally presents later can resolve without treatment despite continuation fingolimod treatment herein report case late onset macular oedema 49yearold woman multiple sclerosis treated fingolimod 7 years patient presented blurred vision eyes visual acuities 20 32 right eye 20 25 left eye macular oedema without discontinuing fingolimod treatment resolved 1 monthpmid33762792 pmcpmc7946040 doi101080 0165810720201821065,0.0
altered brain network function attentionmodulated visual processing multiple sclerosis abstractbackgroundmultiple sclerosis may damage cognitive performance several domains including attention although attention network deficits described rest studies investigate function task performance scarceobjectiveto investigate connectivity within taskrelated networks multiple sclerosis visual attention task function cognitive performancemethodsa total 23 relapsingremitting multiple sclerosis rrms patients 29 healthy controls underwent taskfunctional magnetic resonance imaging fmri scans using visual attention paradigm 3t scanner scans analysed using tensorindependent component analysis tica functional connectivity calculated within components assessed cognitive function brief international cognitive assessment ms bicams batteryresultstica extracted components related visual processing attention executive function defaultmode network subject scores visual attentionrelated executive components greater healthy controls p0032 p0023 connectivity visual attentionrelated defaultmode components higher patients p0043 correlating brief visuospatial memory testrevised bvmtr scores r048 p0036 patients showed reduced connectivity right intraparietal sulcus rips frontal eye field rfef bilateral frontal eye fields p0012 p0003 reduced ripsrfef connectivity came lower symbol digit modalities test sdmt bvmtr scores patients r053 p002 r046 p0049 conclusionattentionrelated networks show altered connectivity task performance rrms patients scaling cognitive disability,0.0
health promoting selfcare behaviors patients multiple sclerosis southeast iran developing model practice basic clin neurosci 2020 sepoct 11 5 687699 doi 1032598 bcn11516701 epub 2020 sep 1abstractintroduction promoting selfcare practice critical strategy enhancing quality life patients multiple sclerosis ms challenging issue study aimed propose model healthpromoting selfcare behaviors ms patientsmethods crosssectional study 200 patients ms referred hospital special diseases kerman city iran chosen main data collection instruments multiple sclerosis knowledge questionnaire rosenberg selfesteem scale multiple sclerosis selfefficacy scale questionnaire perceived barriers benefits selfcare behaviors social support health promotion lifestyle profile ii resilience sense coherence scale data analysis conducted spss v 22 amos18 software structural equation modeling sem also used analysis dataresults model explained 82 variance healthpromoting selfcare behavior hpb results final model obtained sem showed selfefficacy 053 se004 p 0007 selfesteem 039 se004 p0005 social support 036 se004 p0009 sense coherence 034 se007 p0006 resilience 033 se007 p0018 perceived benefits 025 se005 p0009 positive significant relationship hpbconclusion selfcare empowerment model patients ms presented study can used framework designing health promotion interventions improve quality life patients mspmid33643561 pmcpmc7878060 doi1032598 bcn11516701,0.0
burden neurological diseases europe analysis global burden disease study 2017 summarybackgroundneurological disorders account large increasing health burden worldwide shown global burden diseases gbd study 2016 unpacking burden varies regionally nationally important inform public health policy prevention strategies population eu older european region western central eastern europe even older global population suggesting might particularly vulnerable increasing burden agerelated neurological disorders aimed compare burden neurological disorders eu 1990 2017 european region worldwidemethodsthe burden neurological disorders calculated year 2017 incidence prevalence mortality disabilityadjusted lifeyears dalys years life lost years lived disability countries eu european region totally separately diseases analysed alzheimernulls disease dementias epilepsy headache migraine tensiontype headache multiple sclerosis parkinsonnulls disease brain cancer motor neuron diseases neuroinfectious diseases stroke data presented totals sex age year location sociodemographic context shown counts ratesfindingsin 2017 total number dalys attributable neurological disorders 210 million 95 uncertainty interval 185239 eu 411 million 367459 european region total number deaths 11 million 109114 eu 197 million 195201 european region eu neurological disorders ranked third cardiovascular diseases cancers representing 133 103171 total dalys 195 180213 total deaths stroke dementias headache three commonest causes dalys eu stroke also leading cause dalys european region study period found substantial increase allage burden neurodegenerative diseases despite substantial decrease rates stroke infections burden neurological disorders europe higher men women peaked individuals aged 8084 years varied substantially european region country allage dalys deaths prevalence neurological disorders increased allage measures decreased using agestandardised measures three countries azerbaijan turkmenistan uzbekistan decrease mostly attributed reduction premature mortality despite overall increase number dalysinterpretationneurological disorders third common cause disability premature death eu prevalence burden will likely increase progressive ageing european population greater attention neurological diseases must paid health authorities prevention care data presented suggest different priorities health service development resource allocation different countriesfundingeuropean academy neurology,0.0
cognitive impairment multiple sclerosis clinical management mri therapeutic avenues summarymultiple sclerosis chronic demyelinating disease cns cognitive impairment sometimes neglected yet common sign symptom profound effect instrumental activities daily living prevalence cognitive impairment multiple sclerosis varies across lifespan might difficult distinguish causes older age mri studies show widespread changes brain networks contribute cognitive dysfunction grey matter atrophy early sign potential future cognitive decline neuropsychological research suggests cognitive processing speed episodic memory frequently affected cognitive domains narrowing evaluation core areas permits brief routine assessment clinical setting owing brevity reliability sensitivity symbol digit modalities test computerbased analogues can used monitor episodes acute disease activity symbol digit modalities test can also used clinical trials data increasingly show cognitive processing speed memory amenable cognitive training interventions,1.0
cognition multiple sclerosis charcot right charcots early descriptions patients multiple sclerosis noted enfeeblement memory concepts formed slowly along classic triad nystagmus intention tremor ataxic dysarthria 1 charcot trained psychiatry neurology decades neither discipline took note psychological observations psychiatrists 1920s used interviews probe mental status people multiple sclerosis estimates frequency cognitive impairment unreliable ranging two 72 2,0.0
impaired postnatal myelination conditional knockout mouse ferritin heavy chain oligodendroglial cells define importance iron storage oligodendrocyte development function ferritin heavy subunit fth specifically deleted oligodendroglial cells blocking fth synthesis sox10 ng2positive oligodendrocytes first third postnatal week significantly reduces oligodendrocyte iron storage maturation brain fth ko animals presented important decrease expression myelin proteins substantial reduction percentage myelinated axons hypomyelination accompanied decline number myelinating oligodendrocytes reduction proliferating oligodendrocyte progenitor cells opcs importantly deleting fth sox10positive oligodendroglial cells postnatal day 60 effect myelin production oligodendrocyte quantities also tested capacity fthdeficient opcs remyelinate adult brain cuprizone model myelin injury repair fth deletion ng2positive opcs significantly reduces number mature oligodendrocytes myelin production throughout remyelination process furthermore corpus callosum fth ko animals presented significant decrease percentage remyelinated axons substantial reduction average myelin thickness results indicate fth synthesis first three postnatal weeks important appropriate oligodendrocyte development suggest fth iron storage adult opcs also essential effective remyelination mouse brainsignificance statement define importance iron storage oligodendrocyte function deleted ferritin heavy chain fth specifically oligodendrocyte lineage fth ablation oligodendroglial cells throughout early postnatal development significantly reduces oligodendrocyte maturation myelination contrast deletion fth oligodendroglial cells postnatal day 60 effect myelin production oligodendrocyte numbers also tested consequences disrupting fth iron storage oligodendrocyte progenitor cells opcs demyelination found fth deletion ng2positive opcs significantly delays remyelination process adult brain therefore fth iron storage essential early oligodendrocyte development well opc maturation demyelinated adult brain,1.0
secreted glycoprotein reelin suppresses proliferation regulates distribution oligodendrocyte progenitor cells embryonic neocortex oligodendrocyte ol progenitor cells opcs generated proliferate migrate differentiate developing brain although development opcs prerequisite normal brain function molecular mechanisms regulating development neocortex fully understood several molecules regulate tangential distribution opcs developing neocortex cue molecule s regulate radial distribution remains unknown demonstrate secreted glycoprotein reelin suppresses proliferation opcs acts repellent migration vitro functions rely binding reelin receptors signal transduction involving intracellular protein dab1 late embryonic neocortex mice attenuated reelin signaling ie reelin heterozygotedeficient dab1 heterozygotedeficient mutant lowdensity lipoprotein receptor vldlr deficient mice number opcs increased distribution shifted toward superficial layers contrast number opcs decreased tended distribute deep layers neocortex mice abrogated inactivation reelin proteolytic cleavage namely disintegrin metalloproteinase thrombospondin type 1 motifs 3 adamts3 deficient mice cleavageresistant reelin knockin mice male female animals used data indicate reelindab1 signaling regulates proliferation radial distribution opcs late embryonic neocortex regulation reelin function specific proteolysis required normal development opcssignificance statement report reelindab1 signaling regulates proliferation radial distribution opcs late embryonic mouse neocortex oligodendrocyte ol progenitor cells opcs express reelin signaling molecules respond reelin stimulation reelindab1 signaling suppresses proliferation opcs vitro vivo reelin repels opcs vitro radial distribution opcs altered mice either attenuated augmented reelindab1 signaling first report identifying secreted molecule plays role radial distribution opcs late embryonic neocortex results also show regulation reelin function specific proteolysis important normal development opcs,0.0
regional global perspectives incidence multiple sclerosis neuromyelitis optica spectrum disorders asia emphasis china cns inflammatory disorders multiple sclerosis ms neuromyelitis optica neuromyelitis optica spectrum disorders nmo nmosd assuming increasing importance recent years within asia 1 lancet regional health western pacific decai tian colleagues china highlight important new data two nationwide studies ms nmo nmosd first time giving incidence ms nmo nmosd children adults well burden disease terms hospitalization duration reimbursement costs mortality common associated comorbidities rarely reported 1 2 study encompasses one largest asian populations sampled date better case ascertainments inclusivity paediatric diverse populations studies large nationwide populationbased studies ms nmo nmosd country houses fifth worlds population tian et al accessed information national database hospital quality monitoring system hqms covers entire chinese population mainly tertiary hospitals authors identified 1665 hospitals covering 90 tertiary public hospitals 11 973 newly diagnosed nmo nmosd patients 9879 pts ms 20162018 1 2 though heterogeneity methodology prevents head head comparisons studies important points gleaned follows ms study large southeast east asian standards although smaller comparatively absolute numbers studies west asia united states us continental europe oceania 3 4 nmo nmosd study one largest populationbased nmo nmosd studies date terms absolute numbers 1 2 5 7 8 also noteworthy study done post availability anti aqp4 ig g antibody testing ipnd 2015 criteria nmo nmosd resulting better case ascertainment 5 7 8 tian et al reported incidence ms nmo nmosd adults children studies within asia globally paediatric ms nmosd6 7 recent metaanalysis global paediatric ms incidence 087 per 100 000 annually current study 6 7 japanese study nmosd reported rates 006 per 100 000 paediatrics comparable tian et als current study 7 early global ms nmo nmosd studies collected hospital academic institutionbased data within small regions country case ascertainment abstracted standard diagnostic criteria good starting points regional populationbased studies rarely reflected nationwide data projecting estimates one regions entire country uncertain validity longterm instance local malaysian study looking small region within country underestimated true occurrence nmo nmosd within certain ethnic groups country leading underrepresentation cases within malay indian cohorts 8 though efforts reporting commendable leads conflicts health care planning national level unequal disease sociodemographic profiling similar nationwide study showed prevalence nmo nmosd amongst malays chinese indians 09 09 06 per 100 000 n260 256 19 9 therefore tian et als study utilizing hqms database careful case ascertainment inclusive comprehensive looks regions increases relevance covering large population nationwide rather extrapolating small region 1 2 estimated age sex adjusted incidence ms groups namely adults comparable asian reports wherein overall incidence ms ranged 05 078 per 100 000 malaysia taiwan japan korea respectively 1 2 3 4 9 10 however rates though increasing still low compared high incidence areas western asia like iran 34 per 100 000 us europe scandinavia russia australia new zealand ranges 1 10 per 100 000 3 4 10 study substantiated recently published atlas ms 3rd edition prevalence ms china reported doubled 3 4 thus though incidence increasing asia complex interactions genetic susceptibility environment plausibly accounts ms partiality west asia western populations 3 4 alternatively incidence nmo nmosd present study high comparable rates japan taiwan korea malaysia ranging age adjusted 0287 adults0347 per 100 000 china 050073 per 100 000 population south asian countries 1 2 8 9 10 11 rates higher reported caucasian studies nearly comparable afroamerican carribean reports 5 8 tian et als study interestingly highlights variability nmo nmosd certain ethnic groups gender regions within asia high nmo nmosd ms ratios large numbers reported chinese cohort also seen asian cohorts malaysia nmosd commoner amongst chinese nmosd ms ratios 21 compared indians msnmosd 831 malays msnmosd 21 9 recent australianew zealand study also found asians 3 times prone nmo nmosd caucasians 11 authors identified female predominance ms nmosd notably higher amongst nmosd patients ie 2047 ms nmosd female preponderance especially nmosd also seen asian ms nmosd studies japan korea hong kong taiwan malaysia 5 9 nmo nmosd studies us europe australia new zealand west asia india also reveal similar female predominance though less marked east asian studies 5 8 11 uniquely tian et als study ms reaffirmed important effects latitude seen japanese studies us europe russia australia new zealand 3 4 however study identified negative northsouth gradient also negative westeast altitude gradient identified ms latitude preponderance seen nmosd incidence study similar reports australia new zealand thus suggesting genetic factors pathogenesis 1 2 11 terms burden disease tian et als study reports mortality rates ms nmo nmosd 6 7 per 1000 years occurrence associated comorbidities hypertension conditions whilst autoimmune diseases sle sjorgen syndromes seen nmosd ms past mortality morbidity scarcely explored regional studies ms nmo nmosd 1 2 authors also assessed burden disease terms hospitalization costs duration associated comorbidities data vital budget impact analysis studies health care planning medication procurement regionally therefore tian et als study hospitalization burden cost timely facilitate ms nmo nmosd resource allocations advent newer sophisticated disease modifying therapies immunosuppressants biologics ms nmo nmosd 1 2 additionally study reports presence universal government based social health insurance successfully improved access care ms nmosd patients china 1 2 summary authors provided important updated nationwide information epidemiology burden cost disease china careful case ascertainment shows similarities regional asian studies adds current worldwide literature ms nmo nmosd,0.0
robust deep learningbased segmentation glioblastoma routine clinical mri scans using sparsified training radiol artif intell 2020 sep 30 2 5 e190103 doi 101148 ryai2020190103 ecollection 2020 sepabstractpurpose improve robustness deep learningbased glioblastoma segmentation clinical setting sparsified datasetsmaterials methods retrospective study preoperative t1weighted t2weighted t2weighted fluidattenuated inversion recovery postcontrast t1weighted mri 117 patients median age 64 years interquartile range iqr 5573 years 76 men included within multimodal brain tumor image segmentation brats dataset plus clinical dataset 20122013 similar imaging modalities 634 patients median age 59 years iqr 4969 years 382 men glioblastoma six hospitals used expert tumor delineations postcontrast images available various clinical datasets one sequences missing convolutional neural network deepmedic trained combinations complete incomplete data without sitespecific data sparsified training introduced randomly simulated missing sequences training effects sparsified training centerspecific training tested using wilcoxon signed rank tests paired measurementsresults model trained exclusively brats data reached median dice score 081 segmentation brats test data 049 clinical data sparsified training improved performance adjusted p 05 even excluding test data missing sequences median dice score 067 inclusion sitespecific data sparsified training led higher model performance dice scores greater 08 par model based complete incomplete data model using brats clinical training data inclusion sitespecific data sparsified training consequenceconclusion accurate automatic segmentation glioblastoma clinical scans feasible using model based large heterogeneous partially incomplete datasets sparsified training may boost performance smaller model based public sitespecific datasupplemental material available articlepublished cc 40 licensepmid33937837 pmcpmc8082349 doi101148 ryai2020190103,0.0
intracortical motor conduction associated hand dexterity progressive multiple sclerosis abstractbackgroundhand dexterity dysfunction key feature disability people progressive multiple sclerosis pms underlies corticospinal tract cst cerebellar integrity well disruption cortical networks hardly assessed standard techniques transcranial magnetic stimulation promising tool evaluating integrity intracortical motor pathwaysobjectiveto investigate neurophysiological correlates motor hand impairment pmsmethodsanteroposterior ap stimulation primary motor cortex activates cst indirectly polysynaptic pathways direct cst activation occurs lateromedial lm directed current thirty pms 15 healthy controls underwent dominant hand motor evoked potentials mep using ap lmdirected stimulation clinical assessment dexterity ninehole peg test strength mrc scale grip pinch resultspms aplm latency difference 25 standard deviation mean controls 33 showed worse dexterity difference upper limb strength accordingly aplm latency shortening predicted dexterity r20538 p0001 strength impairment contrary absolute mep latencies correlated strength grip r20381 p0014 mrc r20184 p0041 conclusionaplm latency shortening may used assess integrity polysynaptic intracortical networks implicated dexterity impairment,0.0
early evidence disease activity fingolimod predicts mediumterm inefficacy relapsingremitting multiple sclerosis abstractbackgroundfingolimod fty effective secondline drug relapsingremitting multiple sclerosis 50 patients showing evidence disease activity neda 2years nonetheless early identification nonresponders extremely important promptly address aggressive drugsobjectivesthis cohort study evaluates fty mediumterm effectiveness searching early markers treatment failurepatients methodsthree hundred eighty patients starting fty enrolled classified according neda time first relapse criteria 4year followup logistic cox regression analyses applied identify early predictors nonresponseresultsat 4years 656 patients free relapses 354 neda female gender associated higher risk nonresponse moreover evidence clinical magnetic resonance imaging mri activity first year treatment highly predictive disease activity followup positive predictive value nonresponse 074 presence 1 relapse 073 presence 1 active mri lesion 083 presence clinical mri activityconclusionsfty effectiveness persists mediumterm followup close monitoring first year treatment warranted early identify nonresponders requiring treatment optimization,0.0
anxiety depression affect performance symbol digit modalities test time ms immune disorders abstractbackgroundlongitudinal studies assessing depression anxiety effects cognition multiple sclerosis ms limitedobjectivewe tested whether withinperson fluctuations symptoms depression anxiety time affect cognition persons ms inflammatory bowel disease ibd rheumatoid arthritis ra lifetime history depression anxiety disorders dep anx without immunemediated inflammatory diseases imid methodswe followed participants ms 255 ibd 247 ra 154 dep anx 306 3years annually completed hospital anxiety depression scale hads cognitive tests including symbol digit modalities test sdmt evaluated associations elevated symptoms scores11 anxiety hadsa depression hadsd sdmt zscores using multivariable linear modelsestimating betweenperson withinperson effectsresultsparticipants ms performed worse sdmt participants dep anx cohort 068 95 ci 088 048 participants elevated hadsa scores performed worse sdmt without elevated scores 043 95 ci 065 021 particularly ra timevarying withinperson elevations depressive symptoms associated worse sdmt performance 012 95 ci 021 0021 conclusionsacross persons elevated symptoms anxiety adversely affected information processing elevated symptoms depression withinpersons time associated declines information processing speed,0.0
mtor inhibitor therapy tuberous sclerosis complex longitudinal study muscle mass determined abdominal crosssectional imaging ct mri radiol imaging cancer 2020 sep 18 2 5 e190091 doi 101148 rycan2020190091 ecollection 2020 sepabstractpurpose determine effect chronic mammalian target rapamycin mtor inhibition skeletal muscle mass patients tuberous sclerosis complex tsc materials methods retrospective study patients tsc taking mtor inhibitors underwent least two abdominal ct mri examinations 2005 2017 included n 24 14 males mean age 145 years 78 standard deviation first examination one reviewer drew regions interest around psoas muscles l3 measure crosssectional area multiple linear mixedeffect modeling performed evaluate association muscle mass covariates timeresults 24 patients underwent total 129 abdominal ct mri examinations median duration mtor inhibition last examination 106 months range 13103717 days significant association duration mtor inhibitor therapy psoas muscle area multiple linear mixedeffect modeling p 055 however patient height height squared significant predictors psoas area p 014 p 0001 respectively conclusion duration mtor inhibition tsc significantly associated decrease psoas muscle area suggesting chronic mtor inhibition associated sarcopeniakeywords ct mrimaging pediatrics rsna 2020pmid33778734 pmcpmc7983794 doi101148 rycan2020190091,0.0
mri correlates clinical disability handmotor performance multiple sclerosis phenotypes abstractbackgroundhandmotor impairment affects large proportion multiple sclerosis ms patients however substrates still poorly understoodobjectivesto investigate association global disability handmotor impairment alterations motorrelevant structural functional magnetic resonance imaging mri networks ms patients different clinical phenotypesmethodsone hundred thirtyfour healthy controls hc 364 ms patients 250 relapsingremitting ms rrms 114 progressive ms pms underwent expanded disability status scale edss rating ninehole peg test 9hpt electronic finger tapping rate eftr structural resting state rs functional mri scans used perform sourcebased morphometry gray matter gm components analyze white matter wm tract diffusivity indices perform rs seedbased approach primary motor cortex involved hand movement handmotor cortex random forest analyses identified predictors clinical impairmentresultin rrms global measures atrophy lesions together measures structural damage motorrelated regions predicted edss outofbag oob r2019 prange0001004 z9hpt right oobr2014 left oobr2024 prange0001003 rs functional connectivity fc abnormalities identified rrms models pms cerebellar sensorimotor regions atrophy cerebellar peduncles integrity increased rs fc left handmotor cortex right inferior frontal gyrus predicted edss obbr2016 prange002004 conclusionin rrms measures structural damage contribute explain motor impairment whereas structural functional mri measures predict clinical disability pms multiparametric mri approach relevant investigate handmotor impairment different ms phenotypes,0.0
defective cd19+cd24hicd38hi transitional bcell function patients relapsingremitting ms abstractbackgroundmultiple sclerosis ms characterized central nervous system cns infiltration t b cells excess inflammatory cytokine chemokine production failure immune regulation cd19+cd24hicd38hi transitional b cells producing interleukin il 10 shown suppress interferon ifn tumour necrosis factor tnf production cd4+ t cells dysfunctional autoimmune arthritis systemic lupus erythematosusobjectivewe hypothesized transitional bcelldependent immune regulation defective ms examined function healthy subjects patients relapsingremitting multiple sclerosis rrms methodsa total 62 healthy donors 21 rrms subjects donated peripheral blood study il10producing b cells ifn tnfproducing t cells proliferating t cells quantified flow cytometryresultsin healthy individuals cd19+cd24hicd38hi transitional b cells produce il10 cd19+cd24+cd38+ naive cd19+cd24hicd38 memory b cells able suppress cd4+ tcell proliferation ifn tnfproduction subjects rrms cd19+cd24hicd38hi transitional b cells produce significantly less il10 fail suppress effector tcell functionconclusioncd19+cd24hicd38hi transitional b cells physiologically represent potent regulatory bcell subset functionally defective patients rrms abnormality may contribute immune pathological process,0.0
nicotinic acetylcholine receptors 7 9 modifies tobacco smoke risk multiple sclerosis abstractintroductiontobacco smoke exposure established risk factor multiple sclerosis ms yet confers risk known evidence observational studies suggests nicotine may protective component animal studies support hypothesis demonstrating nicotines protective effect ms mediated presence absence 7 9 nicotinic acetylcholine receptors nachrs respectivelyobjectiveto determine variation genes encoding 7 9 nachrs cholinergic receptor nicotinic alpha 7 chrna7 alpha 9 chrna9 will modify ms risk conferred tobacco smokingmethodsa multistage geneenvironment ge framework utilized including casecontrol analysis 286 cases 176 controls haplotype genebased analyses followed extension caseonly 1053 cases analysis overlapping variantsresultsthe results suggest chrna7 chrna9 modifies ms risk conferred tobacco smoke risk among smokers increased carriers minor chrna9 haplotype noncarriers minor chrna7 haplotype findings consistent pharmacology receptors animal studies msconclusionthis study implicates novel processes ms initiation demonstrate need ge studies advancing understanding missing heritability ms,0.0
feelings depression pain walking difficulties largest impact quality life people multiple sclerosis irrespective clinical phenotype abstractbackgroundthe symptoms largest impact healthrelated quality life hrqol people multiple sclerosis ms may vary ms phenotype relapsingremitting ms rrms secondary progressive ms spms primary progressive ms ppms knowing symptoms assists symptom managementobjectiveto examine associations 13 common ms symptoms hrqol total sample stratified ms phenotypemethodthe study included 1985 participants hrqol measured two multiattribute utility instruments assessment quality life eight dimensions aqol8d european quality life five dimensions five levels dimension eq5d5l multivariable linear regression used identify symptoms largest impact hrqolsresultsfeelings depression pain fatigue feelings anxiety strongly associated aqol8d eq5d5l walking difficulties additionally contributed reduced eq5d5l strongest single predictors multivariable analyses feelings depression pain aqol8d walking difficulties eq5d5l irrespective ms phenotypeconclusionthe strongest single predictors aqol8d eq5d5l feelings depression pain walking difficulties irrespective ms phenotype reducing symptoms may largest impact improving hrqol ms phenotypes people ms,0.0
oculomotor fatigue neuropsychological assessments mirror multiple sclerosis fatigue j eye mov res 2020 sep 13 13 4 doi 1016910 jemr1346abstractfatigue major complaint ms now objective assessment tools established hampers treatment approach previous work indicated association fatigue cognitive measures attention oculomotor tests established healthy individuals readout fatigue extent ms patients based observations compared two groups ms patients one fatigue n28 one without fatigue n21 group healthy subjects n15 standardised computerised measure alertness oculomotor stress test patients fatigue showed highly significant changes saccade dynamics defined main sequence phase plane plots showed slowing saccades characteristical fatigue double peak asymmetrical phase plane oculomotor tests differentiated significantly fatigue fatigabiliy ms patients also showed significantly worse performance alertness test well oculomotor task significantly slower reaction times observed tonic alertness 2 series without cue p025 p037 phasic alertness cue p24 p34 performance influenced disability well affective state conclude controlling disability depression saccadic stress tests alertness tests used objective readout fatigability fatigue ms patientspmid33828807 pmcpmc8006090 doi1016910 jemr1346,0.0
mogigg1 coexistence neuronal autoantibodies abstractbackgroundthe presence coexistent neuronal antibodies neuronaligg patients myelin oligodendrocyte glycoprotein immunoglobulin g mogigg1 yet well understoodobjectivesthe aim study investigate coexistence broad range neuronaligg mogigg1+ patientsmethodsmogigg1+ patients tested 17 neuronaliggs cerebrospinal fluid csf serum including nmdarigg amparigg gababrigg lgi1igg caspr2igg gabaarigg gad65igg mglur1igg dppxigg crmp5igg amphiphysinigg pca1 2 tr anna1 2 3 clinical radiological features mogigg1+ nmdarigg csf compared control cohort mogigg1+ patients without nmdariggresultsa total 376 mogigg1+ patients underwent testing neuronaliggs serum testing neuronaliggs 113 adults 142 children identified one child nmdarigg 07 one child caspr2igg 07 one adult lgi1igg 09 one adult gabaarigg 09 csf testing neuronaliggs 97 adults 169 children identified seven children 4 seven adults 7 nmdarigg one adult gabaarigg 1 mogigg1+ nmdarigg+ patients median age 17 range 239 years features associated mogigg1+ nmdarigg+ included encephalopathy p0001 seizures p0045 leptomeningeal enhancement p0045 conclusionnmdarigg frequently detected neuronaligg coexist mogigg1 mogigg1+ nmdarigg+ patients often presented encephalopathy seizures testing mogigg1 nmdarigg may warranted patients encephalopathy inflammatory demyelinating syndromes,1.0
role sacral neuromodulation patients neurogenic lower urinary tract dysfunction purpose review current literature regarding sacral neuromodulation snm neurogenic lower urinary tract dysfunction nlutd focused indications barriers latest technological developments material methods pubmed database search performed april 2020 focusing snm various neurourological conditions results snm increasingly indicated lower urinary tract dysfunction lutd neurourological patients studies cases series several methodological limitations limited followup lacking standardized definition snm clinical success series focused neurogenic overactive bladder spinal cord injured incomplete lesions multiple sclerosis patients barriers applying therapy neurogenic lutd mainly related magnetic resonance imaging incompatibility size implantable pulse generator ipg battery depletion newer technological advances made address limitations will widely available near future conclusions snm seems promising therapy neurogenic lutd carefully selected patients incomplete lesions studies still needed define subgroups neurological patients benefit minimally invasive technique,0.0
depression associated disconnection neurotransmitterrelated nuclei multiple sclerosis abstractbackgrounddepression frequently associated multiple sclerosis ms however biological background underlying association poorly understoodobjectiveinvestigating functional connections neurotransmitterrelated brainstem nuclei along relationship white matter wm microstructure ms patients depressive symptomatology msd without depressive symptomatology msnd methodscombined restingstate functional magnetic resonance imaging fmri diffusionweighted mri dmri study 50 ms patients including 19 msd 31 msnd patients along 37 healthy controls hc main analyses performed 1 comparison groups raphe nuclei rn related functional connectivity fc 2 correlation rnrelated fc whole brain dmriderived fractional anisotropy fa map 3 comparison groups fa rnrelated wm arearesults 1 rnrelated fc reduced msd compared msnd hc 2 rnrelated fc positively correlated fa wm cluster mainly encompassing thalamic basal ganglia regions including fornix 3 fa wm area reduced msdconclusiondepressive symptomatology ms specifically associated functional disconnection neurotransmitterrelated nuclei turn may traced distinct spatial pattern wm alterations mainly involving limbic network,0.0
highintensity interval training reduces neutrophiltolymphocyte ratio persons multiple sclerosis inpatient rehabilitation abstractin persons multiple sclerosis pwms neutrophiltolymphocyte ratio nlr associated disability status symptomatology disease activity highintensity interval training hiit improves many symptoms pwms may positively influence disease progression present results randomized controlled trial inpatient rehabilitation immediate single bout training 3week intervention effects hiit versus moderate continuous training nlr related cellular inflammation markers hiit reduced nlr 3week intervention period training effects might due repetitive inflammatory states compensatory antiinflammatory counterbalancing hiit session,0.0
risk factors leaving employment due multiple sclerosis changes risk past decades using competing risk survival analysis abstractbackgroundno studies assessed changes employment survival multiple sclerosis ms populations recent decades including introduction diseasemodifying therapies dmts objectivesto evaluate factors associated leaving employment due ms assess whether risk leaving employment changed recent decades australia stratified ms phenotypemethodswe included 1240 participants working ms diagnosis information employment status reasons leaving employment year leaving collected data analysed using competing risk survival analysisresultsmales progressive ms lower education level older age diagnosis associated higher subdistribution hazard leaving employment compared period 2010 subdistribution hazard 20102016 relapsingremitting multiple sclerosis rrms reduced 43 subdistribution hazard ratio shr 067 95 confidence interval ci 050 090 significant reduction seen primaryprogressive multiple sclerosis ppms shr 125 95 ci 072 216 secondaryprogressive multiple sclerosis spms shr 137 95 ci 084 225 conclusionmales people progressive ms lower education level higher risk leaving employment differential changed risk leaving employment people different ms phenotype 2010 coincides increased usage highefficacy dmts rrms,0.0
toleranceinducing medicines autoimmunity rheumatology beyond summaryautoimmunity currently managed generalised immunosuppression associated serious sideeffects infection cancer ideal treatment strategy induce immune toleranceie reprogramme immune system stop recognising host threat drugfree remission follow intervention representing change approach treatment autoimmune disease tolerance induction achievable animal models autoimmunity translation clinic slow nonetheless progress madeeg restoration therapeutic responsiveness drugfree remission achieved stem cell transplantation refractory autoimmunity significant delays onset type 1 diabetes individuals high risk achieved following brief treatment anticd3 monoclonal antibody future antigenspecific interventions provide highly targeted personalised approaches avoiding generalised immunosuppression entirely trials already started using direct autoantigenic peptide administration cellular therapies modalities series paper discuss history immune tolerance induction focus rheumatological disease also highlighting essential data specialties propose key unanswered questions will covered papers series,0.0
virdb 20 interactive analysis comorbidity conditions associated vitiligo pathogenesis using coexpression networkbased approach f1000res 2020 aug 27 91055 doi 1012688 f1000research257131 ecollection 2020abstractvitiligo disease mysterious origins context occurrence pathogenesis autoinflammatory theory perhaps widely accepted theory discusses occurrence vitiligo theory elaborates clinical association vitiligo autoimmune disorders psoriasis multiple sclerosis rheumatoid arthritis diabetes present work discuss comprehensive set differentially coexpressed genes involved crosstalk events vitiligo associated autoimmune disorders psoriasis multiple sclerosis rheumatoid arthritis progress previous tool vitiligo information resource virdb incorporate compendium vitiligorelated multiomics datasets present virdb 20 available webresource consisting statistically sound manually curated information virdb 20 integrative database datasets connected kegg string genecards swissprot npass present study communicate major updates expansions virdb deliver new version virdb 20 virdb 20 offers maximum user interactivity along ease navigation envision virdb 20 will pertinent researchers clinicians engaged drug development vitiligopmid33763205 pmcpmc7953917 doi1012688 f1000research257131,0.0
spinal wnt5a plays key role spinal dendritic spine remodeling neuropathic inflammatory pain models proalgesic effects peripheral wnt3a wnt signaling represents highly versatile signaling system plays critical roles developmental morphogenesis well synaptic physiology adult life implicated variety neural disorders recently demonstrated wnt3a able recruit multiple noncanonical signaling pathways alter peripheral sensory neuron function nociceptive modalityspecific manner furthermore several studies recently reported important role wnt5a acting via canonical noncanonical signaling spinal processing nociception number pathologic pain disorders using diverse molecular genetic behavioral approaches mouse models pain vivo report novel role wnt5a signaling nociceptive modulation structural level models chronic pain using male female mice found wnt5a released spinally peripheral sensory neurons recruits tyrosine kinase receptors ror2 ryk modulate dendritic spine rearrangement blocking wnt5aryk ror2 axis spinal dorsal horn neurons prevented activitydependent dendritic spine remodeling significantly reduced mechanical hypersensitivity induced peripheral injury well inflammation moreover observed peripheral wnt3a signaling triggers release wnt5a spinal cord inhibition spinal wnt5a signaling attenuates functional impact peripheral wnt3a nociceptive sensitivity conclusion study reports novel role wnt signaling axis coordinating peripheral spinal sensitization shows targeting wnt5aryk ror2 signaling alleviates structural functional mechanisms nociceptive hypersensitivity models chronic pain vivosignificance statement major need elucidate molecular mechanisms underlying chronic pain disorders develop novel therapeutic approaches wnt signaling represents highly versatile signaling system plays critical roles development adult physiology implicated several diseases including chronic pain conditions using mouse models study identifies novel role wnt5a signaling nociceptive modulation spinal cord level observed wnt5a recruits ror2 ryk receptors enhance dendritic spine density leading nociceptive sensitization blocking wnt5aryk ror2 interaction spinal dorsal horn prevented spine remodeling significantly reduced inflammatory neuropathic hypersensitivity findings provide proofofconcept targeting spinal wnt signaling alleviating nociceptive hypersensitivity vivo,0.0
deescalating rituximab dose results stability clinical radiological serum neurofilament levels multiple sclerosis abstractbackgroundphase ii observational studies support use rituximab multiple sclerosis standard protocols lacking studies suggest comparable efficacy low highdose regimensobjectiveto evaluate effectiveness safety deescalating rituximab dose 1000 500mg 6months multiple sclerosismethodspatients switched rituximab 1000 500mg 6months prospectively followed 12months relapses disability occurrence brain spinal magnetic resonance imaging mri lesions serum neurofilament light chain nfl cd19+b cell igg concentrations analyzedresultsfiftynine patients included 37 relapsingremitting 22 secondary progressive relapses occurred difference expanded disability status scale edss baseline 4 2545 12months 35 2555 p0284 overall three new t2 lesions appeared followup nfl concentration stable baseline 79 59452 pg ml 12months 91 59213 pg ml p0120 igg concentrations decreased greater rituximab load coefficient0439 p0041 igg deficient patients greater risk infections or627 95 ci171229 p0005 conclusiondeescalating rituximab dose 1000 500mg 6months safe results clinical radiological stability affect serum nfl 12months rituximab load negatively influences igg concentrations igg deficient patients higher risk infections,0.0
adverse event profile differences rituximab ocrelizumab findings fda adverse event reporting database abstractbackgroundrituximab ocrelizumab anticd20 monoclonal antibodies shown marked reduction multiple sclerosis ms inflammatory activity however realworld safety profile adequately comparedobjectiveto investigate adverse event ae profile rituximab ocrelizumab reported food drug administration adverse event reporting system faers databasemethodsthe faers database filtered indication ms drug rituximab ocrelizumab disproportionality analyses including limited reporting odds ratio ror conducted identify drugae associations signal detected lower limit 95 confidence interval ror ror025 exceeded 1resultsthere 623 7948 reports rituximab ocrelizumab respectively frequent aes rituximab ocrelizumab infusionrelated reaction 482 urinary tract infection 1052 respectively strongest drugae association rituximab ocrelizumab ear pruritus ror025 4753 oral herpes ror025 3899 respectively ocrelizumab associated almost two times higher frequency infections rituximab 2193 vs 1105 respectively conclusionthis study revealed differences reporting aes rituximab ocrelizumab infections reported frequently ocrelizumab although speculative potentially different extensive bcell depletion ocrelizumab might explain findings additional pharmacovigilance studies need performed better characterize differences ae profile bcelldepleting therapies,0.0
inflammatory activity following motor progression due critical cns demyelinating lesions abstractbackgroundnew inflammatory activity unclear frequency clinical significance progressive multiple sclerosis ms uncertain patient cohorts motor progression due critical demyelinating lesionsobjectivesthe aim study determine likelihood central nervous system cns inflammatory activity assessed new clinical relapses active magnetic resonance imaging mri lesions following onset motor progression due critical demyelinating lesionsmethodspatients progressive upper motor neuron impairment 1year attributable critical demyelinating lesions single cns lesion progressive solitary sclerosis pss 2 5 total cns demyelinating lesions progressive paucisclerosis pps 5 cns demyelinating lesions progressive exclusively unilateral monoparesis hemiparesis puhms identified clinical data reviewed acute ms relapses subsequent mri reviewed active t1gadoliniumenhancing t2demyelinating lesionsresultsnone 91 patients 22 pss 40 pps 29 puhms identified experienced clinical relapses median clinical followup 93months range 12518months nine patients 10 developed active lesions median 84 months radiologic followup range 12518months active lesions occurred 24 puhms 5 pss 3 pps cohortsconclusionnew inflammatory activity defined active lesions clinical relapses following motor progression patients critical demyelinating lesions low diseasemodifying therapies reduce demyelinating relapses active mri lesions uncertain benefit cohorts,1.0
developmental analysis juxtavascular microglia dynamics interactions vasculature microglia resident cns macrophage dynamic cells constantly extending retracting processes contact functionally regulate neurons glial cells far less known microgliavascular interactions particularly healthy steadystate conditions use male female mouse cerebral cortex show higher percentage microglia associate vasculature first week postnatal development compared older ages timing associations dependent fractalkine receptor cx3cr1 similar developmental microgliavascular associations detected human brain using live imaging mice found juxtavascular microglia migrated microglia actively colonizing cortex became stationary adulthood occupy vascular space nearly 2 months juxtavascular microglia ages associate vascular areas void astrocyte endfeet developmental shift microglial migratory behavior along vessels corresponded astrocyte endfeet fully ensheath vessels together data provide comprehensive assessment microgliavascular interactions support mechanism microglia use vasculature migrate within developing brain parenchyma migration becomes restricted arrival astrocyte endfeet juxtavascular microglia become highly stationary stable mature cortexsignificance statement report first extensive analysis juxtavascular microglia healthy developing adult brain live imaging revealed juxtavascular microglia within cortex highly motile migrate along vessels colonizing cortical regions using confocal expansion superresolution electron microscopy determined microglia associate vasculature ages areas lacking full astrocyte endfoot coverage motility juxtavascular microglia ceases astrocyte endfeet fully ensheath vasculature data lay fundamental groundwork investigate microgliaastrocyte cross talk juxtavascular microglial function healthy diseased brain provide potential mechanism vascular interactions facilitate microglial colonization brain later regulate neural circuit development,0.0
nfb activation accounts cytoprotective effects perk activation oligodendrocytes eae previous studies demonstrate activation pancreatic er kinase perk protects oligodendrocytes inflammation experimental autoimmune encephalomyelitis eae model multiple sclerosis ms interestingly data indicate cytoprotective effects perk activation oligodendrocytes eae mediated activating transcription factor 4 atf4 accompanied activation nuclear factor b nfb nfb plays critical role ms eae however effects nfb activation oligodendrocytes diseases remain elusive herein generated mouse model allow activation nfb specifically oligodendrocytes found enhanced nfb activation oligodendrocytes minimal effect viability function normal conditions male female mice interestingly found enhanced nfb activation oligodendrocytes attenuated eae disease severity ameliorated eaeinduced oligodendrocyte loss demyelination axon degeneration without affecting inflammation female mice moreover showed detrimental effects perk inactivation oligodendrocytes eae accompanied impaired nfb activation oligodendrocytes completely rescued enhanced nfb activation oligodendrocytes female mice findings suggest nfb activation accounts cytoprotective effects perk activation oligodendrocytes ms eaesignificance statement nuclear factor b nfb activated oligodendrocytes multiple sclerosis ms animal model experimental autoimmune encephalomyelitis eae however role nfb activation oligodendrocytes ms eae remains elusive herein generated mouse model allows activation nfb selectively oligodendrocytes demonstrated nfb activation prevented oligodendrocyte death myelin damage eae model demonstrated nfb activation contributed protective effects pancreatic er kinase perk activation oligodendrocytes eae model work will facilitate development new treatments enhance oligodendrocyte survival ms patients targeting perknfb pathway,1.0
clinical mri characteristics multiple sclerosis patients middle eastern north african ancestry residing ontario canada abstractbackgroundmultiple sclerosis ms incidence rising traditionally lowburden regions including middle east north africa mena objectivesour objective evaluate disease characteristics ms patients mena descent menams methodsmenams patients age sexmatched ms patients european descent eurms identified ms clinic registry st michaels hospital toronto canada disease activity severity evaluated annualized relapse rate arr magnetic resonance imaging mri activity change expanded disability status scale edss progression index pi ms severity score msss resultsall ms patients within registry identified mena origin n192 age sexmatched eurms patients included mean age 429years 67 female total 25 24 eurms menams progressive disease similar mean disease durations 115 114years respectively clinical radiological disease activity arr proportion new enlarging mri lesions similar menams showed greater disability progression time edss change024 vs 006 p001 higher msss 312 vs 267 p004 higher pi 034 vs 027 p007 conclusionmenams patients demonstrate higher disease severity compared eurms patients despite similar inflammatory measures disease activity disability progression absence relapses observations illustrate importance intersections environmental socioeconomic genetic determinants optimizing individualized ms care,0.0
autofluorescence spectroscopy proxy chronic white matter pathology abstractbackgroundthe balance tissue injury repair ultimately determines outcomes chronic neurological disorders progressive multiple sclerosis ms however extent pathology can difficult detect particularly insidious offset tissue regenerationobjectivesthe objective research evaluate whether tissue autofluorescencetypically source contaminationprovides surrogate marker white matter injurymethodstissue autofluorescence autopsied specimens experimental clinical characterized spectral confocal microscopy correlated severity chronicity determined standard histopathologyresultsmonths cuprizone cpz induced demyelination despite robust remyelination autofluorescent deposits progressively accumulated regions prior pathology autofluorescent deposits likely reflecting myelin debris remnants conspicuously localized white matter proportional lesion severity displayed differential fluorescence time strikingly similar features apparent also autopsied ms tissueconclusionautofluorescence spectroscopy illuminates prior ongoing white matter injury accumulation autofluorescence proportion extent progressive atrophy despite robust remyelination cpz brain provides important proofofconcept phenomenon insidious ongoing damage masked mechanisms tissue repair hypothesize highly relevant progressive phase ms,1.0
conscientiousness deterioration employment status multiple sclerosis 3years abstractbackgroundphysical cognitive symptoms multiple sclerosis ms correlate unemployment crosssectionally prospective studies rarely published accounted personality traits conscientiousnessmethodsin 3year study 70 people ms pwms 25 healthy controls hcs evaluated employment status using online interviews capturing hours worked negative work events employee relations accommodations deteriorating employment status des defined reduced employment fulltime parttime negative work events pwms explored workplace accommodations disclosure disease status physical psychological predictors des eg conscientiousness resultsat followup des 0 hcs 257 ms 627 workstable pwms used least one work accommodation frequently flexible hours baseline despwms lower education p0009 lower conscientiousness p0001 fatigue p0033 performed worse symbol digit modalities test p0013 brief visuospatial memory testrevised p0041 ninehole peg test p0046 relative workstable model predicting des significant 2 7 30936 p0001 baseline conscientiousness accounted variance des p0004 factors higher conscientiousness pwms likely disclose condition work p0038 conclusionaccommodations low conscientiousness flexible hours physical cognitive rehabilitation may prevent des,0.0
incidence multiple sclerosis china nationwide hospitalbased study background multiple sclerosis ms leading cause disability among young adults effects considerable social economic burdens data ms incidence china national level lacking conducted first nationwide hospitalbased study estimate incidence hospitalization burden ms china methods study based administrative database national hospital quality monitoring system covers 1665 tertiary hospitals mainland china medical record homepage patients including 346 variables including demographic characteristics diagnoses procedures expenses etc uniformly collected across tertiary hospital via standard protocol ms defined 2010 international panel criteria ms identified icd10 code g350 findings identified 27 336 hospital admissions 15 060 ms patients 2016 2018 amongst patients 9 879 newly diagnosed age sexadjusted incidence per 100 000 personyears 0235 95 confidence interval ci 02300240 0055 00500060 children 0288 02820294 adults respectively female male ratio 202 peak disease onset age 4049 years residents highlatitude highaltitude areas likely develop ms f 899 p 0001 prevalent comorbidities include hypertension 188 diabetes 72 stroke 147 depression anxiety 37 autoimmune disease 23 20162018 104 adults 2 children died hospital mortality rate 99 per 1 000 personyears interpretation first time obtain national incidence ms 0055 children 0288 adults per 100 000 china geographical distribution ms incidence presented northsouth latitude gradient westeast altitude gradient funding national science foundation china 81801199 91642205 81830038 advanced innovation center human brain protection capital medical university beijing,0.0
nwasp regulates oligodendrocyte myelination oligodendrocyte myelination depends actin cytoskeleton rearrangement neural wiskottaldrich syndrome protein nwasp actin nucleation factor promotes polymerization branched actin filaments nwasp activity essential myelin membrane wrapping schwann cells role oligodendrocytes cns myelination remains unknown report oligodendrocytesspecific deletion nwasp mice sexes resulted hypomyelination ie reduced number myelinated axons thinner myelin profiles well substantial focal hypermyelination reflected formation remarkably long myelin outfolds myelin outfolds surrounded unmyelinated axons neuronal cell bodies myelin profiles latter configuration resulted pseudomultimyelin profiles often associated axonal detachment degeneration throughout cns including optic nerve corpus callosum spinal cord furthermore developmental analysis revealed myelin abnormalities already observed onset myelination suggesting formed aberrant misguided elongation oligodendrocyte inner lip membrane results demonstrate nwasp required formation normal myelin cns also reveal nwasp plays distinct role oligodendrocytes compared schwann cells highlighting difference regulation actin dynamics cns pns myelinationsignificance statement myelin critical normal function nervous system facilitating fast conduction action potentials process myelination cns oligodendrocytes undergo extensive morphological changes involve cellular process extension retraction axonal ensheathment myelin membrane wrapping present evidence nwasp protein regulating actin filament assembly arp2 3 complexdependent actin nucleation plays critical role cns myelination absence leads several myelin abnormalities data provide important step understanding molecular mechanisms underlying cns myelination,1.0
central vein sign multiple sclerosis patients vascular comorbidities abstractbackgroundthe central vein sign cvs imaging biomarker able differentiate multiple sclerosis ms conditions causing similar appearance lesions magnetic resonance imaging mri including cerebral small vessel disease csvd however impact vascular risk factors vrfs csvd percentage cvs positive cvs+ lesions ms never evaluatedobjectiveto investigate association different vrfs percentage cvs+ lesions msmethodsin 50 ms patients 3t brain mris including highresolution 3dimensional t2weighted images analyzed presence cvs mri markers csvd backward stepwise regression model used predict combined predictive effect vrf ie age hypertension diabetes obesity eversmoking hypercholesterolemia mri markers csvd cvsresultsthe median frequency cvs+ lesions 71 range 35100 univariate analysis age p00001 hypertension p0001 diabetes p001 obesity p001 smoking p005 presence enlargedperivascularspaces mri p0005 associated lower percentage cvs+ lesions stepwise regression model showed age arterial hypertension associated percentage cvs+ lesions ms adjusted r2046 p00001 p001 respectively conclusionthe proportion cvs+ lesions significantly decreases older hypertensive ms patients although study conducted patients already established ms diagnosis diagnostic yield previously proposed 35 cvs proportionbased diagnostic threshold appears affected overall results suggest presence vrf csvd taken account cvs assessment,0.0
predictors trainingrelated improvement visuomotor performance patients multiple sclerosis behavioural mri study abstractbackgroundthe development tailored recoveryoriented strategies multiple sclerosis requires early identification individuals potential functional recoveryobjectiveto identify predictors visuomotor performance improvements proxy functional recovery using predictive statistical model combines demographic clinical magnetic resonance imaging mri datamethodsrighthanded multiple sclerosis patients underwent baseline disability assessment mri brain structure function vascular health subsequently undertook 4 weeks right upper limb visuomotor practice changes performance practice outcome measure identified predictors improvement training set patients using lasso regression calculated best performing model validation set applied model test setresultspatients improved visuomotor performance practice younger age better visuomotor abilities less severe disease burden concurrent use preventive treatments predicted improvements neuroimaging localised outcomerelevant sensory motor regions microstructure activity correlated performance improvementsconclusioninitial characteristics including age disease duration visuospatial abilities hand dexterity selfevaluated disease impact presence diseasemodifying treatments can predict functional recovery individual patients potentially improving clinical management stratification clinical trials mri correlate outcome potentially supporting individual prognosis,0.0
remyelination multiple sclerosis basic science clinical translation summarythe treatment multiple sclerosis transformed successful development immunotherapies efficiently reduce disease activity related clinical relapses relapsingremitting phase disease however prevention disability progression due axonal neuronal damage loss yet achieved therapeutically challenging particularly progressive phase disease one strategy counteract neurodegeneration promote neuroprotection enhancing myelin regeneration hence restoring nerve conduction metabolic support axon animal studies provided targets interventions improve brain spinal cord remyelination paving way translation research humans initial promising forays problems emerged including questions best design clinical trials appropriately measure outcomes solving problems will need additional work efficacious proremyelination therapies will ready people multiple sclerosis real sense hope researchers getting closer successful therapy,1.0
catherine lubetzkiexpert remyelination multiple sclerosis early medical training paris v university paris france catherine lubetzki developed interest neurology chance random selection process left last year group allowed choose rotationand left neurosurgery rotation department gerard guyot renowned neurosurgeon wonderful person really beginning passion neurology says lubetzki now professor neurology sorbonne university head department neurology coordinator multiple sclerosis centre salptrire hospital paris france,1.0
methylome transcriptome signature bronchoalveolar cells multiple sclerosis patients relation smoking abstractbackgrounddespite compelling evidence cigarette smoking impacts risk developing multiple sclerosis ms little known smokingassociated changes primary exposed lung cells patientsobjectiveswe aimed examine molecular changes occurring bronchoalveolar lavage bal cells ms patients relation smoking comparison healthy controls hcs methodswe profiled dna methylation bal cells female ms n17 hc n22 individuals using illumina infinium epic performed rnasequencing nonsmokersresultsthe prominent changes found relation smoking 1376 cpg sites adjusted p005 differing ms smokers nonsmokers approximately 30 affected genes overlapped smokingassociated changes hc leading strong common smoking signature ms hc gene ontology analysis smoking ms patients resulted additional discrete changes related neuronal processes methylome transcriptome analyses nonsmokers suggest bal cells ms patients display subtle reaching adjusted p005 concordant changes genes connected reduced transcriptional translational processes enhanced cellular motilityconclusionsour study provides insights impact smoking lung inflammation immunopathogenesis ms,0.0
high prudent diet factor score predicts lower relapse hazard early multiple sclerosis abstractbackgrounddietary patterns association subsequent clinical course well studied early multiple sclerosis ms objectivesto describe dietary patterns people 5years following first clinical demyelination assess associations ms conversion relapsemethodsthis study included baseline food frequency questionnaire dietary intake entry ausimmune study 5year followup iterated principal factor analysis applied ms conversion relapse risks assessed cox proportional hazards models adjusted age sex study site education body mass index bmi smoking omega3 supplement useresultsin cases first clinical diagnosis central nervous system cns demyelination identified three major dietary patterns prudent highvegetable mixed explaining 43 37 24 diet variance dietary intake respectively fruits vegetables fish wholegrains nuts loaded highly prudent pattern starchy vegetables legumes highvegetable pattern meats alcohol mixed pattern diet factor scores associated ms conversion risk baseline prudent scores median significantly lower relapse risk adjusted hazard ratio054 95 confidence interval ci 037 081 evidence plateau effectconclusionprudent diet factor score median prospectively associated lower relapse risk 5years following first clinical demyelinating event,1.0
#39 maybe losing sight human dimension#39 physicians#39 approaches existential spiritual religious needs among patients chronic pain multiple sclerosis qualitative interviewstudy health psychol behav med 2020 jul 23 8 1 248269 doi 101080 2164285020201792308abstractobjective research suggests existential spiritual religious issues important patients psychological adjustment living chronic pain multiple sclerosis however paucity studies investigating physicians experience approach patients needsdesign physicians experiences approaches existential spiritual religious needs treating chronic pain multiple sclerosis studied eight semistructured interviews analysed using interpretative phenomenological analysis ipa results physicians found patients spiritual religious needs however experienced every patient struggling existential challenges related illness rooted changed identity approaching death physicians approached needs appeared influenced six conditions medical culture training role experiences time pressure personal interests interpersonal approachconclusion physicians training seems better suited meet biomedical objectives patients concrete needs patients wish relational meeting focused subjective lifeworld challenge discussed relation modern patientcenteredness doctorpatient relationship culturally constructed experiences privacy future clinical practice research needspmid34040871 pmcpmc8114351 doi101080 2164285020201792308,0.0
fetal hlag mediated immune tolerance interferon response preeclampsia abstractbackgroundfetal immune tolerance crucial pregnancy success studied link preeclampsia severe pregnancy disorder uncertain pathogenesis fetal human leukocyte antigen g hlag genes regulating maternal immune responsesmethodswe assessed sex ratios regulatory hlag haplotypes population cohorts series preeclampsia stillbirth studied placental mrna expression 136 genes sequencing hlag interferon alpha ifn protein expression immunohistochemistryfindingswe found underrepresentation males preeclamptic births especially delivered preterm small gestational age balancing selection hlag associated sex ratio stillbirth preeclampsia observed downregulation hlag receptors many tolerogenic genes marked upregulation ifna1 preeclamptic placentasinterpretationthese findings indicate evolutionary tradeoff immune tolerance protection infections maternalfetal interface promotes genetic diversity fetal hlag thereby affecting survival preeclampsia sex ratio highlight ifna1 potential mediator preeclampsia target therapeutic trialsfundingfinnish medical foundation pivikki sakari sohlberg foundation karolinska institutet research foundation scandinaviajapan sasakawa foundation japan eye bank association astellas foundation research metabolic disorders japan society promotion science knut alice wallenberg foundation swedish research council medical society liv och hlsa sigrid juslius foundation helsinki university hospital university helsinki jane aatos erkko foundation academy finland finska lkaresllskapet novo nordisk foundation finnish foundation pediatric research emil aaltonen foundation,0.0
safety acceptability clozapine risperidone progressive multiple sclerosis phase randomised blinded placebocontrolled trial bmj neurol open 2020 jul 9 2 1 e000060 doi 101136 bmjno2020000060 ecollection 2020abstractobjective clozapine risperidone shown reduce neuroinflammation humans mice clozapine risperidone progressive multiple sclerosis crisp trial conducted determine whether clozapine risperidone suitable progressive multiple sclerosis pms methods crisp trial actrn12616000178448 blinded randomised placebocontrolled trial three parallel arms n12 arm participants pms randomised clozapine 100150 mg day risperidone 2035 mg day placebo 6 months primary outcome measures safety adverse events aes serious adverse events sae acceptability treatment satisfaction questionnaire medication9 results interim analysis n9 revealed significant differences timeontrial treatment groups placebo p0030 0025 clozapine risperidone respectively participants receiving clozapine withdrawn titration period mean dose3515 mg day participants receiving clozapine risperidone reported significantly higher rate aes placebo p000001 saes specifically low doses clozapine appeared cause acute doserelated intoxicant effect patients pms fairly severe chronic spastic ataxic gait worsening mobility resolved drug cessationinterpretation crisp trial results suggest patients pms may experience increased sensitivity clozapine risperidone indicate dose titration schedule developed schizophrenia may suitable pms findings negate potential drugs reduce multiple sclerosisassociated neuroinflammation highlight need research understand pharmacodynamic profile effect clozapine risperidone patients pmstrial registration number actrn12616000178448pmid33681788 pmcpmc7903182 doi101136 bmjno2020000060,0.0
cardiac rhabdomyoma surrogate diagnosis tuberous sclerosis complex newborn baby case report tikur anbessa university hospital ethiop j health sci 2020 jul 1 30 4 639642 doi 104314 ejhsv30i419abstractbackground neonatal tuberous sclerosis complex autosomal dominant inherited disease characterized high rate neurological cardiac skin manifestationscase presentation reported 4 days old female neonate respiratory distress tachypnea tachycardia hypomelanotic macular lesions chest xray echocardiographic studies revealed cardiomegaly multiple echogenic masses left right ventricles suggestive cardiac rhabdomyoma furthermore noncontrast brain magnetic resonance imaging revealed subependymal nodules cortical tubers therefore clinical diagnosis neonatal tuberous sclerosis complex heart failure made patient initiated diuretic treatment oxygen nasal catheter subsequent improvement seizure occurred yet last three half years followup currently patient thriving well symptomsconclusion detection prenatal early neonatal age cardiac rhabdomyoma useful clue diagnosis tuberous sclerosis complex neonates proper clinical evaluation patients time first contact prevents missing findings skin macules chest xray findings helped us diagnose tuberous sclerosis complex present casepmid33897224 pmcpmc8054458 doi104314 ejhsv30i419,0.0
behavioral neural signatures working memory childhood working memory function changes across development varies across individuals patterns behavior brain function track individual differences working memory human development however well understood establish associations working memory cognitive abilities functional mri fmri activation data 11 500 9 10yearold children sexes enrolled adolescent brain cognitive development abcd study ongoing longitudinal study united states behavioral analyses reveal robust relationships working memory shortterm memory language skills fluid intelligence analyses relating outofscanner working memory performance memoryrelated fmri activation emotional nback task demonstrate frontoparietal activity working memory challenge indexes working memory performance relationship domain specific fmri activation related emotion processing emotional nback task inhibitory control stopsignal task sst reward processing monetary incentive delay mid task track memory abilities together results inform understanding individual differences working memory childhood lay groundwork characterizing ways change across adolescencesignificance statement working memory foundational cognitive ability changes time varies across individuals analyze data 11 500 9 10yearolds establish relationships working memory cognitive abilities frontoparietal brain activity working memory challenge cognitive challenges results lay groundwork assessing longitudinal changes working memory predicting later academic realworld outcomes,0.0
regulatory b cells normalize cns myeloid cell content mouse model multiple sclerosis promote oligodendrogenesis remyelination unmet medical need patients multiple sclerosis ms inexorable loss cns myelin latterly neurons leading permanent neurologic disability solicitation endogenous oligodendrocytes progenitor cells precursor oligodendrocytes remyelinate axons may abort onset disability female mice experimental autoimmune encephalomyelitis eae murine model ms adoptive transfer il10+ regulatory b cells bregs shown reverse eae promoting expansion peripheral cnsinfiltrating il10+ t cells examined whether bregs treatment bystander effect regulatory t cells associated cns repair reflected oligodendrogenesis remyelination found transfusion bregs reverses established clinical eae clinical improvement associated significant increase spinal cord remyelination reflected gratio analysis within thoracic lumbar spine observed spinal cords eae bregstreated mice cns resident cd11b cd45intly6c microglia infiltrating cd11b+ cd45high monocytes macrophages content reverts normal polarize m2like cd206+ phenotype concurrently substantial increase neooligodendrogenesis manifest increase cd45 low cns cells expressing a2b5 early marker oligodendrocytes progenitor cell differentiation well galc+ o1+ premyelinating myelin basic protein+ myelin oligodendrocyte glycoprotein+ mature oligodendrocytes reciprocal downregulation paired related homeobox protein 1 results demonstrate clinical benefit bregs associated normalization cns immune milieu concurrent activation oligodendrocyte progenitor cells subsequent remyelinationsignificance statement multiple sclerosis patients demyelination progresses aging disease course leading irreversible disability study discovered using mouse model multiple sclerosis transfusion autologous regulatory b cells bregs able ameliorate cure sustain durable remission disease show adoptive transfer bregs dramatically decreased frequency myeloidderived cells infiltrating monocytes macrophages resident microglia converted phenotype immunosuppressivelike phenotype moreover showed cns oligodendrocyte progenitor cells activated following bregs treatment differentiate myelinating oligodendrocytes results neooligodendrogenesis remyelination spinal cords,1.0
thoracic flexion provokes circumferential dysesthesia symptom thoracic cord lesions ms abstractthoracic flexion rapid forward flexion waist can elicit circumferential electrical sensation patients multiple sclerosis clinical radiographic features phenomenon described symptom typically sensory band around t6t7 dermatomes usually associated recent thoracic cord lesions clinically independent cervical pathology lhermittes sign similar vertical radiation symptoms upon neck flexion due cervical cord lesions sign may help localize ms plaques thoracic cord even thoracic mri negative,0.0
hospital diagnosed pneumonia age 20 years multiple sclerosis risk bmj neurol open 2020 jun 16 2 1 e000044 doi 101136 bmjno2020000044 ecollection 2020abstractintroduction respiratory inflammation proposed risk factor ms study aims determine hospitaldiagnosed pneumonia adolescence age 20 years associated subsequent multiple sclerosis ms methods casecontrol study included incident ms cases age 20 years identified using swedish national registers cases matched 10 general population controls age sex region pneumonia diagnoses identified 05 610 1115 1620 years age conditional logistic regression models adjusted infectious mononucleosis im education calculated ors 95 cis urinary tract infections utis common complication ms age 20 years included control diagnosis reverse causationresults 6109 cases 49 479 controls included pneumonia diagnosed age 1115 years associated subsequent ms adj 200 95 ci 122 327 although statistically significant sensitivity analyses showed similar magnitude associations pneumonia age 1115 years ms statistically significant associations ms pneumonia age groups observed adjustment im notable effect associations statistically significantly associated ms utis associated msconclusion pneumonia 1115 years age associated ms suggesting possible role inflammation respiratory system aetiology ms period susceptibility adolescence research respiratory infections prior ms onset conducted replicate finding determine explanatory causal mechanismspmid33681783 pmcpmc7903180 doi101136 bmjno2020000044,0.0
effectiveness interventions targeting spasticity functional clinical outcomes patients multiple sclerosis systematic review clinical trialsselect available,0.0
reduced expression pp2a methylesterase pme1 pp2a methyltransferase lcmt1 alters sensitivity betaamyloidinduced cognitive electrophysiological impairments mice betaamyloid thought play critical role alzheimer9s disease ad application soluble oligomeric forms produces adlike impairments cognition synaptic plasticity experimental systems found previously transgenic overexpression pp2a methylesterase pme1 pp2a methyltransferase lcmt1 altered sensitivity mice ainduced impairments suggesting pme1 inhibition may effective approach preventing treating impairments explore possibility examined behavioral electrophysiological effects acutely applied synthetic oligomers male female mice heterozygous either pme1 ko lcmt1 genetrap mutation found heterozygous pme1 ko mice resistant ainduced impairments cognition synaptic plasticity whereas lcmt1 genetrap mice showed increased sensitivity ainduced impairments heterozygous pme1 ko mice produced normal levels endogenous exhibited normal electrophysiological responses picomolar concentrations suggesting reduced pme1 expression animals protects ainduced impairments without impacting normal physiological functions together data provide additional support roles pme1 lcmt1 regulating sensitivity ainduced impairments suggest inhibition pme1 may constitute viable therapeutic approach selectively protecting pathologic actions adsignificance statement elevated levels amyloid brain thought contribute cognitive impairments observed alzheimer9s disease patients show genetically reducing endogenous levels pp2a methylesterase pme1 prevents cognitive electrophysiological impairments caused acute exposure pathologic concentrations without impairing normal physiological function endogenous production conversely reducing endogenous levels pp2a methyltransferase lcmt1 increases sensitivity ainduced impairments data offer additional insights molecular factors control sensitivity ainduced impairments suggest inhibiting pme1 may constitute viable therapeutic avenue preventing arelated impairments alzheimer9s disease,0.0
idebenone distinct effects mitochondrial respiration cortical astrocytes compared cortical neurons due differential nqo1 activity idebenone synthetic quinone reduction cells can bypass mitochondrial complex defects donating electrons complex iii drug used clinically treat complex disease leber9s hereditary optic neuropathy lhon less successful clinical trials neurodegenerative diseases nad p hquinone oxidoreductase 1 nqo1 appears main intracellular enzyme catalyzing idebenone reduction however nqo1 universally expressed cells brain using primary rat cortical cells pooled sexes tested hypotheses level endogenous nqo1 activity limits ability neurons astrocytes use idebenone electron donor support mitochondrial respiration tested prediction nqo1 induction pharmacological activation transcription factor nuclear erythroid 2related factor 2 nrf2 enables idebenone bypass complex cells poor nqo1 expression found idebenone stimulated respiration astrocytes reduced respiratory capacity neurons importantly idebenone supported mitochondrial oxygen consumption presence complex inhibitor astrocytes neurons ability reversed inhibiting nqo1 conversely recombinant nqo1 delivery neurons prevented respiratory impairment conferred complex bypass activity nrf2 activators failed increase nqo1 neurons carnosic acid induced nqo1 cos7 cells expressed little endogenous enzyme carnosic acididebenone combination treatment promoted nqo1dependent complex bypass activity cells thus combination drug strategies targeting nqo1 may promote repurposing idebenone additional disorderssignificance statement idebenone used clinically treat loss visual acuity leber9s hereditary optic neuropathy clinical trials several additional diseases failed study demonstrates fundamental difference way idebenone affects mitochondrial respiration cortical neurons compared cortical astrocytes cortical neurons unable use idebenone direct mitochondrial electron donor due nqo1 deficiency results suggest idebenone behaves nqo1dependent prodrug raising possibility lack neuronal nqo1 activity contributed limited efficacy idebenone neurodegenerative disease treatment combination therapy drugs able safely induce nqo1 neurons well brain cell types may able unlock neuroprotective therapeutic potential idebenone related quinones,1.0
dendritic spine dynamics peripheral nerve injury intravital structural study neuropathic pain intractable medical condition options effective treatment emerging evidence shows strong structurefunction relationship dendritic spine dysgenesis presence neuropathic pain postmortem tissue analyses can imply dynamic structural changes associated injuryinduced pain profiled vivo dynamics dendritic spines time superficial dorsal horn lamina ii neurons peripheral nerve injuryinduced pain used twophoton wholeanimal imaging paradigm permitted repeat imaging dendritic branches neurons c57 bl6 thy1yfp male mice study demonstrates first time ongoing steadystate changes dendritic spine dynamics dorsal horn associated peripheral nerve injury pain ultimately relationship altered dendritic spine dynamics neuropathic pain may serve structurebased opportunity investigate mechanisms pain following injury diseasesignificance statement work important demonstrates first time 1 powerful utility intravital study dendritic spine dynamics superficial dorsal horn 2 nerve injuryinduced pain triggers changes dendritic spine steadystate behavior spinal cord dorsal horn 3 work opens door investigations vivo spinal cord dendritic spine dynamics context injury disease,0.0
mouse synuclein promotermediated gene expression editing mammalian retinal ganglion cells optic neuropathies group optic nerve diseases caused various insults including glaucoma inflammation ischemia trauma genetic deficits characterized retinal ganglion cell rgc death degeneration increasing number genes involved rgc intrinsic signaling found promising neural repair targets can potentially modulated directly gene therapy can achieve rgc specific gene targeting address challenge first used adenoassociated virus aav mediated gene transfer perform lowthroughput vivo screening male female mouse eyes identified mouse synuclein msncg promoter specifically potently sustained transgene expression mouse rgcs also works human rgcs demonstrated gene therapy combines aavmsncg promoter clustered regularly interspaced short palindromic repeats crispr cas9 gene editing can knock prodegenerative genes rgcs provide effective neuroprotection optic neuropathiessignificance statement present rgcspecific promoter mouse synuclein msncg promoter perform extensive characterization proofofconcept studies msncg promotermediated gene expression clustered regularly interspaced short palindromic repeats crispr cas9 gene editing rgcs vivo knowledge first report demonstrating vivo neuroprotection injured rgcs optic nerve aavmediated crispr cas9 inhibition genes critical neurodegeneration represents powerful tool achieve rgcspecific gene modulation also opens promising gene therapy strategy optic neuropathies common form eye diseases cause irreversible blindness,0.0
neonatal stroke tlr1 2 ligand recruit myeloid cells choroid plexus cx3cr1ccr2 contextspecific manner neonatal stroke frequent stroke elderly many pathophysiological injury aspects distinct neonates including immune signaling myeloid cells can traffic brain via multiple routes choroid plexus cp identified uniquely educated gate immune cell traffic health disease understand mechanisms myeloid cell trafficking via cp influence neonatal stroke characterized phenotypes cpinfiltrating myeloid cells transient middle cerebral artery occlusion tmcao neonatal mice sexes relation bloodbrain barrier permeability injury microglial activation cx3cr1ccr2 signaling focusing dynamics early reperfusion demonstrate rapid recruitment multiple myeloid phenotypes cp ipsilateral injury including inflammatory cd45+cd11b+ly6chighcd86+ beneficial cd45+cd11b+ly6clowcd206+ cd45+cd11b+ly6clowly6ghigh cells minor leukocyte infiltration acutely ischemicreperfused cortex negligible vascular albumin leakage report cx3cr1ccr2mediated myeloid cell recruitment contributes stroke injury considering complexity inflammatory cascades triggered stroke role tlr2 injury also used direct tlr2 stimulation independent injury model tlr2 agonist rapidly recruited myeloid cells cp increased leukocytosis csf blood infiltration cortex remained low time magnitude phenotypes myeloid cells diverged tmcao tlr2 stimulation models disruption cx3cr1ccr2 signaling attenuated monocyte neutrophil trafficking cp cortexsignificance statement stroke neonatal period leads longterm disabilities mechanisms ischemic injury inflammatory response differ greatly immature adult brain examined leukocyte trafficking via choroid plexus cp following neonatal stroke relation bloodbrain barrier integrity injury microglial activation signaling via cx3cr1 ccr2 receptors following direct tlr2 stimulation ischemiareperfusion triggered marked unilateral cx3cr1ccr2 dependent accumulation diverse leukocyte subpopulations cp without inducing extravascular albumin leakage major leukocyte infiltration brain disrupted cx3cr1ccr2 signaling neuroprotective part attenuating monocyte neutrophil trafficking understanding migratory patterns cpinfiltrating myeloid cells intact disrupted cx3cr1ccr2 signaling identify novel therapeutic targets protect neonatal brain,1.0
deletion voltagegated calcium channels astrocytes demyelination reduces brain inflammation promotes myelin regeneration mice determine whether cav12 voltagegated ca2+ channels contribute astrocyte activation generated inducible conditional knockout mouse cav12 subunit deleted gfappositive astrocytes astrocytic cav12 knockout mouse tested cuprizone model myelin injury repair causes astrocyte microglia activation absence lymphocytic response deletion cav12 channels gfappositive astrocytes cuprizoneinduced demyelination leads significant reduction degree astrocyte microglia activation proliferation mice either sex concomitantly production proinflammatory factors tnf il1 tgf1 significantly decreased corpus callosum cortex cav12 knockout mice demyelination furthermore mild inflammatory environment promotes oligodendrocyte progenitor cells maturation myelin regeneration across remyelination phase cuprizone model similar results found animals treated nimodipine cav12 ca2+ channel inhibitor high affinity cns mice either sex injected nimodipine demyelination stage cuprizone treatment displayed reduced number reactive astrocytes showed faster efficient brain remyelination together results indicate cav12 ca2+ channels play crucial role induction proliferation reactive astrocytes demyelination attenuation astrocytic voltagegated ca2+ influx may effective therapy reduce brain inflammation promote myelin recovery demyelinating diseasessignificance statement reducing voltagegated ca2+ influx astrocytes brain demyelination significantly attenuates brain inflammation astrocyte reactivity furthermore changes promote myelin restoration oligodendrocyte maturation throughout remyelination,1.0
minimally invasive oral surgery induction friction chronic neuropathic pain model bio protoc 2020 apr 20 10 8 e3591 doi 1021769 bioprotoc3591 ecollection 2020 apr 20abstractan easily induced preclinical trigeminal neuropathic nerve injury model described study chronic pain model acronym friction foramen rotundum inflammatory constriction trigeminal infraorbital nerve patients neuropathic pain thought related vascular alignment multiple sclerosis along small trigeminal nerve branch v2 innervating maxillary teeth middle third face detectable outward physical signs friction model ideal blinded studies acronym friction applied relates persistence trigeminal neuropathic pain model likely due sliding irritation normal chewing mice stepbystep method induce mild chronic rodent neuropathic pain model described surgery performed orally tiny surgical slit inside cheek crease align chromic gut suture irritant along nerve passes skull model allows testing nonevoked subjective measures evoked quantitative mechanical hypersensitivity allodynia testing von frey filaments least 1014 weeks 100 days anxiety depression behaviors develop within 36 weeks relevant affective component chronic pain many pain drugs failed based testing performed acute animal models available stable easily replicated trigeminal inflammatory compression model better suited understanding mechanistic affective components nerve injuryinduced chronic neuropathic pain states well ideal preclinical trials novel nonopioid pain relief therapiespmid33659557 pmcpmc7842532 doi1021769 bioprotoc3591,0.0
fingolimod rescues demyelination mouse model krabbe#39 s disease krabbe9s disease infantile neurodegenerative disease affected mutations lysosomal enzyme galactocerebrosidase leading accumulation metabolite psychosine shown previously s1p receptor agonist fingolimod fty720 attenuates psychosineinduced glial cell death demyelination vitro ex vivo models data together lack therapies krabbe9s disease prompted current preclinical study examining effects fingolimod twitcher mice murine model krabbe9s disease twitcher mice male female carrying natural mutation galc gene given fingolimod via drinking water 1 mg kg d direct impact fingolimod administration assessed via histochemical biochemical analysis using markers myelin astrocytes microglia neurons globoid cells immune cells effects fingolimod twitching behavior life span also demonstrated results show treatment twitcher mice fingolimod significantly rescued myelin levels compared vehicletreated animals also regulated astrocyte microglial reactivity furthermore nonphosphorylated neurofilament levels decreased indicating neuroprotective neurorestorative processes protective effects fingolimod twitcher mice brain pathology reflected increased life span fingolimodtreated twitcher mice vivo findings corroborate initial vitro studies highlight potential use s1p receptors drug targets treatment krabbe9s diseasesignificance statement study demonstrates administration therapy known fingolimod mouse model krabbe9s disease namely twitcher mouse model significantly rescues myelin levels drug fingolimod also regulates reactivity glial cells astrocytes microglia mouse model protective effects fingolimod result increased life span twitcher mice,1.0
mechanistic target rapamycin regulates oligodendrocyte cytoskeleton myelination differentiation oligodendrocyte precursor cells opcs extend network processes make contact axons initiate myelination recent studies revealed actin polymerization required initiation myelination whereas actin depolymerization promotes myelin wrapping used primary opcs culture isolated neonatal rat cortices sexes young male female mice oligodendrocytespecific deletion mechanistic target rapamycin mtor demonstrate mtor regulates expression specific cytoskeletal targets actin reorganization oligodendrocytes developmental myelination loss inhibition mtor reduced expression profilin2 arpc3 actin polymerizing factors elevated levels active cofilin mediates actin depolymerization deficits actin polymerization revealed reduced phalloidin deficits oligodendrocyte cellular branching complexity peak morphologic differentiation delay initiation myelination show critical role mtor expression localization myelin basic protein mbp mrna mbp protein cellular processes necessary myelin membrane axon wrapping mbp mrna transport deficits confirmed single molecule rna fish moreover expression kinesin family member 1b mbp mrna transport protein reduced cc1+ cells mtor cko mtor inhibited oligodendrocytes undergoing differentiation vitro data support conclusion mtor regulates initiation myelination axon wrapping targeting cytoskeletal reorganization mbp localization oligodendrocyte processessignificance statement myelination essential normal cns development adult axon preservation function mechanistic target rapamycin mtor signaling pathway implicated promoting cns myelination however gap understanding mechanisms mtor promotes developmental myelination regulating specific downstream targets present evidence mtor promotes initiation myelination regulating specific cytoskeletal targets cellular process expansion oligodendrocyte precursor cells well expression cellular localization myelin basic protein,1.0
microglial depletion csf1r inhibitor chronic phase experimental traumatic brain injury reduces neurodegeneration neurological deficits chronic neuroinflammation sustained microglial activation occurs following severe traumatic brain injury tbi believed contribute subsequent neurodegeneration neurological deficits microglia primary innate immune cells brain dependent colony stimulating factor 1 receptor csf1r signaling survival preclinical study examined effects delayed depletion chronically activated microglia functional recovery neurodegeneration 3 months postinjury csf1r inhibitor plexxikon plx 5622 administered adult male c57bl 6j mice 1 month controlled cortical impact remove chronically activated microglia inhibitor withdrawn 1week later allow microglial repopulation following tbi repopulated microglia displayed ramified morphology similar sham uninjured mice whereas microglia vehicletreated tbi mice showed typical chronic posttraumatic hypertrophic morphology plx5622 treatment limited tbiassociated neuropathological changes 3 months postinjury included smaller cortical lesion reduced hippocampal neuron cell death decreased nox2 nlrp3 inflammasomeassociated neuroinflammation furthermore delayed depletion chronically activated microglia tbi led widespread changes cortical transcriptome altered gene pathways involved neuroinflammation oxidative stress neuroplasticity using variety complementary neurobehavioral tests plx5622treated tbi mice also improved longterm motor cognitive function recovery 3 months postinjury together studies demonstrate chronic phase removal neurotoxic microglia tbi using csf1r inhibitors markedly reduce chronic neuroinflammation associated neurodegeneration well related motor cognitive deficitssignificance statement traumatic brain injury tbi debilitating neurological disorder can seriously impact patient9s quality life microglialmediated neuroinflammation induced severe tbi contributes neurological deficits ongoing neurodegenerative processes investigated effect breaking neurotoxic neuroinflammatory loop 1month controlled cortical impact mice pharmacological removal chronically activated microglia using colony stimulating factor 1 receptor csf1r inhibitor plexxikon 5622 overall show shortterm elimination microglia chronic phase tbi followed repopulation results longterm improvements neurological function suppression neuroinflammatory oxidative stress pathways reduction persistent neurodegenerative processes studies clinically relevant support new concepts therapeutic window tbi may far longer traditionally believed chronic evolving microglialmediated neuroinflammation can inhibited regulated precise manner,0.0
effect remote ischaemic preconditioning walking people multiple sclerosis doubleblind randomised controlled trial bmj neurol open 2020 mar 23 2 1 e000022 doi 101136 bmjno2019000022 ecollection 2020abstractbackground remote ischaemic preconditioning ripc exposure body parts brief periods circulatory occlusion reperfusion recent studies also shown ripc can improve exercise performance healthy individualsobjective study aimed assess effect ripc walking people multiple sclerosis ms methods doubleblind randomised controlled clinical trial used three cycles ripc delivered occluding upper arm blood pressure bp cuff inflated pressure 30 mm hg systolic bp patients sham intervention group bp cuff inflated 30 mm hg diastolic bp outcome measures included sixminute walk test 6mwt gait speed borg rate perceived exertion rpe scale tolerability ripc using numerical rating scale discomfort 0 10 adverse events identified responders meeting minimal clinically important difference mcid established literature groupresults seventyfive participants completed study ripc 38 sham 37 distance walked 6mwt improved 19 sham group 57 ripc group p0012 number responders meeting mcid criteria ripc group significantly greater compared sham intervention group serious adverse events occurredconclusion single cycle ripc resulted immediate improvement walking distances 6mwt people mstrial registration numbers nct03153553pmid33681776 pmcpmc7903187 doi101136 bmjno2019000022,0.0
colocalized white matter plasticity increased cerebral blood flow mediate beneficial effect cardiovascular exercise longterm motor learning cardiovascular exercise ce promising intervention strategy facilitate cognition motor learning healthy diseased populations ages ce elevates humoral parameters growth factors stimulates brain changes potentially relevant learning behavioral adaptations however causal relationship ceinduced brain changes human9s ability learn remains unclear tested hypothesis ce elicits positive effect learning via alterations brain structure morphological changes gray white matter function functional connectivity cerebral blood flow resting state conducted randomized controlled trial healthy male female human participants compare effects 2 week ce intervention nonce control group subsequent learning challenging new motor task dynamic balancing dbt 6 consecutive weeks used multimodal neuroimaging t1weighted magnetic resonance imaging mri diffusionweighted mri perfusionweighted mri resting state functional mri investigate neural mechanisms mediating ce learning expected subjects receiving ce subsequently learned dbt higher rate using modified nonparametric combination approach along multiple mediator analysis show learning boost conveyed ceinduced increases cerebral blood flow frontal brain regions changes white matter microstructure frontotemporal fiber tracts study revealed neural mechanisms celearning link within brain probably allowing higher flexibility adapt highly novel environmental stimuli learning complex tasksignificance statement established cardiovascular exercise ce effective approach promote learning memory yet little known underlying neural transfer mechanisms ce acts learning provide evidence ce facilitates learning human participants via plasticity prefrontal white matter tracts colocalized increase cerebral blood flow findings among first demonstrate transfer potential experienceinduced brain plasticity addition practical implications health professionals coaches work paves way future studies investigating effects ce patients suffering prefrontal hypoperfusion white matter diseases,0.0
meningeal lymphangiogenesis enhanced glymphatic activity mice chronically implanted eeg electrodes chronic electroencephalography eeg widely used tool monitoring cortical electrical activity experimental animals although chronic implants allow highquality longterm recordings preclinical studies electrodes foreign objects might therefore expected induce local inflammatory response analyzed effects chronic cranial electrode implantation glymphatic fluid transport provoking structural changes meninges cerebral cortex male female mice immunohistochemical analysis brain tissue dura revealed reactive gliosis cortex underlying electrodes extensive meningeal lymphangiogenesis surrounding dura meningeal lymphangiogenesis also evident mice prepared commonly used chronic cranial window glymphatic influx csf tracer significantly enhanced 30 d postsurgery awake ketaminexylazine anesthetized mice electrodes supporting concept glymphatic influx intracranial lymphatic drainage interconnected altogether experimental results provide clear evidence chronic implantation eeg electrodes associated significant changes brain9s fluid transport system future studies involving eeg recordings chronic cranial windows must consider physiological consequences cranial implants include glial scarring meningeal lymphangiogenesis increased glymphatic activitysignificance statement study shows implantation extradural electrodes provokes meningeal lymphangiogenesis enhanced glymphatic influx csf reactive gliosis analysis based csf tracer injection combination immunohistochemistry showed chronically implanted electroencephalography electrodes surrounded lymphatic sprouts originating lymphatic vasculature along dural sinuses middle meningeal artery likewise chronic cranial windows provoked lymphatic sprouting tracer influx assessed coronal slices increased agreement previous reports identifying close association glymphatic activity meningeal lymphatic vasculature lymphangiogenesis meninges altered glymphatic fluid transport electrode implantation previously described adds new insights foreign body response cns,0.0
granulocytemacrophage colony stimulating factor indirect mediator nociceptor activation pain interaction immune system nervous system center multiple research studies recent years whereas role played cytokines neuronal mediators longer contested mechanisms cytokines modulate pain processing remain elucidated study analyzed involvement granulocytemacrophage colony stimulating factor gmcsf nociceptor activation male female mice previous studies suggested gmcsf might directly activate neurons however established absence functional gmcsf receptor murine nociceptors suggest indirect mechanism action via immune cells report gmcsf applied directly magnetically purified nociceptors induce transcriptional changes nociceptive genes contrast conditioned medium gmcsftreated murine macrophages able drive nociceptor transcription also found conditioned medium nociceptors treated well established pain mediator nerve growth factor also modify macrophage gene transcription providing evidence bidirectional crosstalksignificance statement interaction immune system nervous system known play important role development maintenance chronic pain disorders elucidating mechanisms interactions important step toward understanding therefore treating chronic pain disorders study provides evidence twoway crosstalk macrophages nociceptors peripheral nervous system may contribute sensitization nociceptors cytokines pain development,0.0
interferon plays detrimental role experimental traumatic brain injury enhancing neuroinflammation drives chronic neurodegeneration dna damage type interferons ifns contribute inflammatory responses traumatic brain injury tbi tbiinduced activation microglia peripherallyderived inflammatory macrophages may lead tissue damage neurological deficits investigated role ifn secondary injury tbi using controlled cortical impact model adult male ifndeficient ifn mice assessed posttraumatic neuroinflammatory responses neuropathology longterm functional recovery tbi increased expression dna sensors cyclic gmpamp synthase stimulator interferon genes wildtype wt mice ifn ifnrelated neuroinflammatory genes also upregulated early persistently tbi tbi increased expression proinflammatory mediators cortex hippocampus wt mice whereas levels mitigated ifn mice moreover longterm microglia activation motor cognitive function impairments decreased ifn tbi mice compared injured wt counterparts improved neurological recovery associated reduced lesion volume hippocampal neurodegeneration ifn mice continuous central administration neutralizing antibody ifn receptor ifnar 3 d beginning 30 min postinjury reversed early cognitive impairments tbi mice led transient improvements motor function however antiifnar treatment improve longterm functional recovery decrease tbi neuropathology 28 d postinjury summary tbi induces robust neuroinflammatory response associated increased expression ifn ifnrelated genes inhibition ifn reduces posttraumatic neuroinflammation neurodegeneration resulting improved neurological recovery thus ifn may potential therapeutic target tbisignificance statement tbi frequently causes longterm neurological psychiatric changes head injury patients tbiinduced secondary injury processes including persistent neuroinflammation evolve time can contribute chronic neurological impairments present study demonstrates tbi followed robust activation type ifn pathways implicated microglialassociated neuroinflammation chronic neurodegeneration examined effects genetic pharmacological inhibition ifn key component type ifn mechanisms address role tbi pathophysiology inhibition ifn signaling resulted reduced neuroinflammation attenuated neurobehavioral deficits limited tissue loss long tbi preclinical findings suggest ifn may potential therapeutic target tbi,0.0
nonionotropic action endothelial nmda receptors bloodbrain barrier permeability via rho rockmediated phosphorylation myosin increase bloodbrain barrier bbb permeability crucial step neuroinflammatory processes previously showed n methyl d aspartate receptor nmdars expressed cerebral endothelial cells forming bbb regulate immune cell infiltration across barrier mouse describe mechanism responsible action nmdars bbb permeabilization report mouse cns endothelial nmdars display regulatory glun3a subunit composition confers nmdars9 unconventional properties receptors induce ca2+ influx rather show nonionotropic properties inflammatory conditions costimulation human brain endothelial cells nmda agonists nmda glycine serine protease tissue plasminogen activator previously shown potentiate nmdar activity induces metabotropic signaling via rho rock pathway pathway leads increase permeability via phosphorylation myosin light chain subsequent shrinkage human brain endothelial cells together data draw link nmdars cytoskeleton brain endothelial cells regulates bbb permeability inflammatory conditionssignificance statement authors describe nmdars expressed endothelial cells regulate bloodbrain barrier function via myosin light chain phosphorylation increase permeability report nonneuronal nmdars display distinct structural functional pharmacological features neuronal counterparts,0.0
actinbinding protein cortactin promotes pathogenesis experimental autoimmune encephalomyelitis supporting leukocyte infiltration central nervous system leukocyte entry central nervous system cns essential immune surveillance also basis development pathologic inflammatory conditions within cns multiple sclerosis animal model experimental autoimmune encephalomyelitis eae actinbinding protein cortactin endothelial cells important player regulating interaction immune cells vascular endothelium cortactin shown control integrity endothelial barrier support neutrophil transendothelial migration vitro vivo skin use cortactin geneinactivated male female mice study role protein eae inducing eae immunization myelin oligodendrocyte glycoprotein peptide mog3555 revealed ameliorated disease course cortactin genedeficient female mice compared wt mice however proliferation capacity expression il17a ifn cortactindeficient wt splenocytes differ suggesting lack cortactin affect induction immune response rather cortactin deficiency caused decreased vascular permeability reduced leukocyte infiltration brains spinal cords eae mice accordingly cortactin genedeficient mice smaller numbers proinflammatory cuffs less extensive demyelination reduced expression levels proinflammatory cytokines within neural tissue compared wt littermates thus cortactin contributes development neural inflammation supporting leukocyte transmigration bloodbrain barrier therefore represents potential candidate targeting cns autoimmunitysignificance statement multiple sclerosis autoimmune neuroinflammatory disorder based entry inflammatory leukocytes cns cells cause demyelination neurodegeneration use mouse model multiple sclerosis experimental autoimmune encephalomyelitis show gene inactivation cortactin actin binding protein modulates actin dynamics branching protects neuroinflammation experimental autoimmune encephalomyelitis leukocyte infiltration cns inhibited cortactindeficient mice lack cortactin cultured primary brain endothelial cells inhibited leukocyte transmigration expression levels proinflammatory cytokines cns induction vascular permeability reduced conclude cortactin represents novel potential target treatment multiple sclerosis,1.0
blocking thrombin receptor promotes repair demyelinated lesions adult brain myelin loss limits neurological recovery myelin regeneration critical restoration function recently discovered global knockout thrombin receptor also known protease activated receptor 1 par1 accelerates myelin development demonstrate knocking par1 also promotes myelin regeneration outcomes two unique models myelin injury repair lysolecithin cuprizonemediated demyelination showed par1 knockout male mice improves replenishment myelinating cells remyelinated nerve fibers slows early axon damage improvements myelin regeneration par1 knockout mice occurred tandem skewing reactive astrocyte signatures toward prorepair phenotype cell culture promyelinating effects par1 loss function consistent possible direct effects myelinating potential oligodendrocyte progenitor cells opcs addition opcindirect effects involving enhanced astrocyte expression promyelinating factors bdnf findings highlight previously unrecognized roles par1 myelin regeneration including integrated actions across oligodendrocyte astroglial compartments least partially mechanistically linked powerful bdnftrkb neurotrophic signaling system altogether findings suggest par1 may therapeutically tractable target demyelinating disorders cnssignificance statement replacement oligodendroglia myelin regeneration holds tremendous potential improve function across neurological conditions demonstrate protease activated receptor 1 par1 important regulator capacity myelin regeneration across two experimental murine models myelin injury par1 gproteincoupled receptor densely expressed cns however limited information regarding physiological roles health disease using combination par1 knockout mice oligodendrocyte monocultures oligodendrocyteastrocyte cocultures demonstrate blocking par1 improves myelin production mechanism related effects across glial compartments linked part regulatory actions toward growth factors bdnf findings set stage development new clinically relevant myelin regeneration strategies,1.0
distinct p2y receptors mediate extension retraction microglial processes epileptic peritumoral human tissue microglia exhibit multiple phenotypedependent motility patterns often triggered purinergic stimuli however little data exist motility human microglia pathological situations examine motility microglia stained fluorescent lectin tissue slices female male epileptic patients diagnosed mesial temporal lobe epilepsy cortical glioma peritumoral cortex microglial shape varied ramified amoeboid cells predominantly regions high neuronal loss closer tumor live imaging revealed unstimulated purineinduced microglial motilities including surveillance movements membrane ruffling process extension retraction different concentrations adp triggered opposing motilities low doses triggered process extension suppressed p2y12 receptor antagonists also reduced process length surveillance movements higher purine doses caused process retraction membrane ruffling blocked joint application p2y1 p2y13 receptor antagonists purinergic effects motility similar microglia tested amoeboid ramified cells mesial temporal lobe epilepsy peritumoral cortex tissue expressed p2y12 receptors minority microglia expressed adenosine a2a receptor linked process withdrawal rodent cells lasermediated tissue damage let us test functional significance effects moderate damage induced microglial process extension blocked p2y12 receptor antagonists overall purineinduced motility human microglia epileptic tissue similar rodent microglia p2y12 receptor initiates process extension differs retraction triggered joint activation p2y1 p2y13 receptorssignificance statement microglial cells brainresident immune cells multiple functions healthy diseased brains diverse functions associated distinct phenotypes including different microglial shapes rodent purinergic signaling associated changes cell shape process extension toward tissue damage however little data living human microglia especially diseased states developed reliable technique stain microglia epileptic glioma patients examine responses purines lowintensity purinergic stimuli induced process extension rodents contrast highintensity stimuli triggered process withdrawal mediated p2y1 p2y13 receptors p2y1 p2y13 receptor activation previously linked microglial morphological changes,0.0
integrating crispr engineering hipscderived 2d disease modeling systems human induced pluripotent stem cells hipscs revolutionized research human diseases particularly neurodegenerative psychiatric disorders making possible study mechanisms disease risk initiation otherwise inaccessible patientspecific cells today integration crispr engineering approaches hipscbased models permits precise isogenic comparisons human neurons glia review intended guideline neuroscientists clinicians interested translating research hipscbased studies offers stateoftheart approaches tackling challenges unique human vitro disease models particularly interdonor intradonor variability limitations neuronal maturity circuit complexity finally provide detailed overview immense possibilities field offer highlighting efficient neural differentiation induction strategies major brain cell types providing perspective integrating crisprbased methods study design combination hipscbased disease modeling crispr technology highthroughput approaches promises advance scientific knowledge accelerate progress drug discoverydual perspectives companion paperstudying human neurodevelopment diseases using 3d brain organoids ai tian julien muffat yun li,0.0
activated cx3cl1 smad2 signals prevent neuronal loss alzheimer#39 s tau pathologymediated cognitive dysfunction neurofibrillary tangles likely cause neurodegeneration alzheimer9s disease ad demonstrate cx3cl1 cterminal domain can upregulate neurogenesis may ameliorate neurodegeneration generated transgenic tgcx3cl1 mice overexpressing cx3cl1 neurons tgcx3cl1 mice exhibit enhanced neurogenesis subgranular subventricular zones enhanced neurogenesis correlates well elevated expression tgf2 tgf3 activation downstream signaling molecule smad2 intriguingly enhanced adult neurogenesis mitigated smad2 expression deleted neurons supporting role cx3cl1tgf2 3smad2 pathway control adult neurogenesis tgcx3cl1 mice crossed alzheimer9s ps19 mice overexpress tau p301s mutation exhibit agedependent neurofibrillary tangles neurodegeneration overexpressed cx3cl1 male female mice sufficient rescue neurodegeneration increase survival time improve cognitive function hence provide vivo evidence cx3cl1 strong activator adult neurogenesis reduces neuronal loss improves cognitive function adsignificance statement study will first demonstrate enhanced neurogenesis overexpressed cx3cl1 mitigated disruption smad2 signaling independent interaction cx3cr1 overexpression cx3cl1 lengthens life span ps19 tau mice enhancing adult neurogenesis minimal effect tau pathology enhancing neuronal cx3cl1 mainly cterminal fragment therapeutic strategy blocking reversing neuronal loss alzheimer9s disease related neurodegenerative disease patients,0.0
shortchain fatty acids improve poststroke recovery via immunological mechanisms recovery stroke multicellular process encompassing neurons resident immune cells braininvading cells stroke alters gut microbiome turn considerable impact stroke outcome however mechanisms underlying gutbrain interaction implications longterm recovery largely elusive tested hypothesis shortchain fatty acids scfas key bioactive microbial metabolites missing link along gutbrain axis might able modulate recovery experimental stroke scfa supplementation drinking water male mice significantly improved recovery affected limb motor function using vivo widefield calcium imaging observed scfas induced altered contralesional cortex connectivity associated scfadependent changes spine synapse densities rna sequencing forebrain cortex indicated potential involvement microglial cells contributing structural functional remodeling analyses confirmed substantial impact scfas microglial activation depended recruitment t cells infarcted brain findings identified microbiotaderived scfas modulate poststroke recovery via effects systemic brain resident immune cellssignificance statement previous studies shown bidirectional communication along gutbrain axis stroke stroke alters gut microbiota composition turn microbiota dysbiosis substantial impact stroke outcome modulating immune response however now mediators derived gut microbiome affecting gutimmunebrain axis molecular mechanisms involved process unknown demonstrate shortchain fatty acids fermentation products gut microbiome potent proregenerative modulators poststroke neuronal plasticity various structural levels identified effect mediated via circulating lymphocytes microglial activation results identify shortchain fatty acids missing link along gutbrain axis potential therapeutic improve recovery stroke,0.0
convergence microglia peripheral macrophages phenotype development neuroinflammation differently myeloid cells microglia derive exclusively precursors originating within yolk sac migrate cns development without contribution fetal liver postnatal hematopoiesis consistent unique ontology microglia may express specific physiological markers partly described recent years wondered whether profiles distinguishing microglia peripheral macrophages vary age pathology goal profiled transcriptomes microglia throughout lifespan included parallel comparison peripheral macrophages physiological neuroinflammatory settings using age sexmatched wildtype bone marrow chimera mouse models comprehensive approach demonstrated phenotypic differentiation microglia peripheral macrophages agedependent peripheral macrophages express commonly described microgliaspecific markers early development fcrls p2ry12 tmem119 trem2 chronic neuroinflammation cnsinfiltrating macrophages peripheral myeloid cells acquire microglial markers indicating cns niche may instruct peripheral myeloid cells gain phenotype presumably function microglia cell conclusion data provide evidence plasticity myeloid cell suggest caution strict definition application microgliaspecific markerssignificance statement understanding respective role microglia infiltrating monocytes neuroinflammatory conditions recently seemed possible identification specific microglia signature instead provide evidence peripheral macrophages may express commonly described microglia markers developmental stages pathological conditions particular chronic neuroinflammation data support hypothesis phenotypic plasticity convergence among distinct myeloid cells may act functional unit rather different entities boosting mutual functions different phases disease holds relevant implications view growing use myeloid cell therapies treat brain disease humans,0.0
microrna exosome profiling multiple sclerosis abstractnew dna sequencing technologies uncovered noncoding rna ncrna major player regulating cellular processes can longer dismissed junk dark rna among ncrna microrna mirna arguably extensively characterized category number studies implicated regulating critical functions can influence autoimmune demyelination specific interest multiple sclerosis ms mirna implicated regulating immune responses myelination thus making attractive candidate pharmacological intervention disease biomarkers addition exosomes small vesicles secreted cell types present body fluids also shown play roles immune signaling inflammation angiogenesis therefore exosomes also explored tools therapeutic delivery biomarkers article reviews recent advances mirna exosome profiling ms experimental modelskeywords microrna exosome multiple sclerosis eae biomarker immune responseintroductiondespite remarkable progress understanding treatment multiple sclerosis ms disease course still highly unpredictable1 therefore urgent need exists discovery biomarkers can track predict outcomes related disease progression response therapeutic drugs currently externally validated blood immune marker adequate sensitivity specificity used diagnosis ms probably reflects heterogeneity disease owing progress high throughput sequencing technologies emerging data mechanisms horizontal transfer material cells new opportunities arisen field review discuss currently available evidence associating novel intra extracellular rna analysis putative biomarkers ms well potential role autoimmune demyelination development progressmicrorna nonprotein coding rnasprogress molecular biology last two decades unveiled universe nonprotein coding rna ncrna present cells now apparent protein coding rna represents 2 information encoded genomic dna2 furthermore recent high throughput transcriptome analyses documented ncrna constitutes major product genome3 current knowledge function ncrnas still limited resulting notion just starting understand true value information encoded genomesone best studied groups ncrna microrna mirna mirna conserved singlestranded noncoding rnas comprised approximately 22 nucleotides play important roles generegulation targeting mrnas cleavage translational repression4 master role mirnas regulation gene transcription posttranscriptional level considered epigenetic regulatory mechanism cleaving blocking messenger rnas mrnas translation single mirna can directly repress translation hundreds genes mrna transcript may regulated multiple mirnas manytomany relationship underscores complexity mirna regulatory networks govern cellular programs inflammation neurogenesis homeostatic maintenance several databases online resources available lookup published mirna sequences annotations eg mirbase http mirbaseorg including specialized software find associations given mirna target genes eg mirsystem http mirsystemcgmntuedutw role mirna autoimmune demyelinationthe last decade seen great progress description role mirna ms experimental autoimmune encephalomyelitis eae unbiased transcriptomic analysis functional dissection specific mirnas field flourished one earliest studies mir155 identified key regulator inflammatory responses targeted deletion gene mice resulted decrease th1 th17 cellular differentiation central nervous system cns peripheral lymphoid organs furthermore deletion pharmacological targeting mir155 resulted delayed course reduced severity eae prompted authors study propose therapeutic targeting5 separate study rare form gene mir1553p found drive development autoimmune demyelination regulation heat shock protein 406 mir301a also found critical regulator myelinreactive thelper type 17 cells supporting role candidates therapeutic targets controlling autoimmune demyelination7in addition role modulating effector inflammatory t cell responses mirna also play role regulating regulatory t cell treg population normally counterbalances former surprisingly mir155 also found influence treg development function recent studies showed regulated foxp3 transcription factor characteristic cell population8 seemingly opposite roles mirna different cells highlights complexity regulatory networks play immune systemwhile previous examples highlighted regulatory role mirna proinflammatory responses eae additional studies also showed primary role regulating myelination example mir23aoverexpressing mice increased myelin thickness providing vivo evidence mir23a enhances oligodendrocyte differentiation myelin synthesis9mirna biomarkers msencouraged early discoveries handful mirna involved myelination10 inflammatory responses 11 several studies focused systematic profiling serum biological fluids disease biomarkers one study including 4 observational cohorts 5 mirnas hsamir484 hsamir1405p hsamir320a hsamir4865p hsamir320c showed significant difference patients ms healthy individuals12 followup study explored potential mirna profiling identify subtypes ms study mir92a1 differentially expressed relapsingremitting ms rrms versus secondary progressive ms spms rrms versus healthy controls furthermore mirna showed association expanded disability status scale edss disease duration13in recent study large group ms patients n1 088 stratified based brain imaging mirna profiling used identify differences across different magnetic resonance imaging mri based phenotypes14 interestingly mri phenotype demonstrated mirna signature whose underlying biology implicates bloodbrain barrier bbb pathology specifically mir223p mir3615p mir3455p valid differentiators mri phenotypeswhile mirna profiling biofluids poses great promise biomarker ms must noted conflicting results heterogeneity lack replication ongoing challenges field example recent review literature highlighted 650 differentially expressed ncrnas reported ms patients 275 found dysregulated direction least two independent studies cutoff criteria increased three studies 9 reported differences remain15 lack replication foreign biomarker projects general underscore logistical difficulties behind kind studies challenges eg small sample size biospecimen collection methods profiling techniques etc can overcome appropriate planning funding inherent complexity heterogeneity underlying biology recent emergence novel mechanisms mirna regulation eg circular rnas might provide better insight renewed enthusiasm development robust biomarkers autoimmune demyelination16exosomes celltocell communication systemexosomes small extracellular vesicles released endocytic compartment cells can easily detected serum biological fluids17 contain material cell origin including proteins lipids dna mrna noncoding rna mediate wide array biological functions including modulation immune reactions cell differentiation apoptosis18 exosomes might fact provide mechanism long distance intercellular communication since can travel different compartments body across biological barriers due small size 30120nm lipophilic nature exosomes taken number organ tissues cell populations19 indeed demonstrated cells transfected plasmid coding green fluorescent protein egfp injected mice released exosomes carrying egfp rna found circulation many cell types proving direct interaction exosomes target cells20 production secretion transfer exosomes arises crucial still largely unexplored system celltocell communication cancer research particular provides numerous clues significance exosomemediated effects21 increasing amount recently published literature confirms cancer cancerassociated cells use exosomes communicate message malignant nonmalignant cells2224 done transfer functional components order initiate pathways necessary tumor survival propagation additional roles exosomes include regulation cell proliferation induction programmed cell death metabolism differentiation phenotypic modification25 thus exosomemediated effects likely play role many pathological conditions may contribute every aspect cellular biology dysregulationexosomes contain random sampling components parent cells specific composition reflecting state cell activation can influenced pathologic processes tissue origin indeed exosome release considered cellular adaptation mechanism biogenesis composition secretion affected microenvironment cells furthermore extracellular rna rnabinding proteins cellular proteins differentially expressed exosomes nonvesicle compartments18 thanks recent progress high throughput transcriptome techniques analysis low content material total exosomes become possible26 resulting data provide unique insight wealth transcripts present extracellular vesicles18 27rna species identified cargo cell culture released exosomes include predominantly different classes short rna species including mirna small nuclear rna small nucleolar rna piwiinteracting rna vault rna yrna small conditional rna signal recognition particle rna 7skrna28 furthermore ribosomal rna transfer rna messenger rna long noncoding rnas various intergenic repeats also found within exosomes far studies addressed human biofluidderived exosomes full transcriptome content27 2931 demonstrated wealth sequences present circulating exosomes majority rnas ncrna including mirna studies provided evidence large part cellular transcriptome present exosomes therefore potentially transferred cells complexity exosomal rna cargo combined seclusion circulating rnases provides exciting platform biomarker discovery researchcirculating exosomes biomarkersexosomes provide means celltocell communication transporting cargo delivering target cells content microvesicles representing molecular bioprint parental cells therefore exosomes present blood biofluids potentially noninvasive biomarkers early diagnosis prognosis various types diseases32 exosome profiling often called liquid biopsy may provide insight content hardtoaccess organs without need direct sampling33 exosome release considered cellular adaptation mechanism biogenesis composition secretion affected microenvironment cellscurrently clinicaltrialsgov registry enlists 35 active trials aiming observation exosomes biomarkers analysis majority trials dedicated cancer tumor research one study dedicated neurological condition ie dementia 34 interestingly blood circulating exosomes show presence cns markers resulting brain origin35 36 analysis exosomes provide unique insight status cns bypassing need biopsy37 furthermore exosomes can provide source long sought cns antigens trafficking bbb36 arguments prompt trials involving exosomes analysis cns conditions including msexosomes ms monitoringemerging data use mirna molecular cargo carried circulating exosomes biomarkers various conditions renewed enthusiasm exploring role microvesicles putative indicator ms status disease monitoring38 current search pubmed database using mesh terms exosomes multiple sclerosis following individual curation revealed 16 original publications relating biomarker search ms table 1 majority 9 articles analyzed serum plasmaderived exosomes whereas 3 addressed cerebrospinal fluid csf microvesicles 3 urine 2 described cell cultures frequently analyzed exosomes content mirna 9 papers whereas 3 papers investigated lipids 2 proteins 2 publications aimed global profiling exosomes cargo either rna27 protein39 reports document technical feasibility exosomes extraction subsequent analysis ms patients derived material promising ms biomarkers eg levels blood circulating exosomal mir1225p starting emerge27 40 although number publications significance exosomes analysis biomarkers ms still limited current results encouraging warrant researchtabletable 1 list original publication describing analyzing exosomes biomarkers mstable 1 list original publication describing analyzing exosomes biomarkers msview larger versionconclusion perspectiveslargescale profiling circulating mirna exosome content eae ms prompted early enthusiasm potential emerge longsought biomarker can characterize patient status using minimally invasive approach yet high sensitivity specificity however promising results arisen limited replication high heterogeneity remain unsolved challenges research warranted firmly establish relatively newly discovered biomolecules firm contenders quest ms biomarkerdeclaration conflicting intereststhe author s declared potential conflicts interest respect research authorship publication articlefundingthe author s disclosed receipt following financial support research authorship publication article study supported national center research poland grants 2016 23 b nz6 02541 2015 19 b nz6 02834 national center research development grant eranet_neuron 14 2019 university warmia na mazury olsztyn internal grant mpm additional support received nih ninds r01ns088155 r01ns099240 nmss ca1072a7 dod dod_w81xwh1510652 seb seb heidrich family friends endowed chair neurology ucsf seb holds distinguished professorship neurology ucsforcid idsergio e baranzini https orcidorg 000000030067194x,1.0
tumefactive demyelinating lesions patient multiple sclerosis developed two days injection rituximab acta neurol taiwan 2020 dec 29 4 124127abstractbackground rituximab increasingly prescribed treatment multiple sclerosis ms recent years tumefactive demyelinating lesions can occur onset course ms another major cause lesions side effects drugs natalizumab fingolimod study case report young ms patient suffered tumefactive lesions following injection rituximabcase presentation patient 18yearold man ms developed double vision imbalance quadriparesis symptoms followed decrease consciousness two days administration rituximab tumefactive lesions observed patients brain magnetic resonance imaging mri conclusion rituximab considered potential cause tumefactive demyelinating lesions patients mspmid34018172,1.0
clinical perspective practices pleural effusions chronic systemic inflammatory diseases breathe sheff 2020 dec 16 4 200203 doi 101183 2073473502032020abstractsystemic inflammatory diseases heterogeneous family autoimmune chronic inflammatory disorders affect multiple systems within human body connective tissue disease ctd large group within family characterised immunemediated inflammation connective tissue group disorders often associated pleural manifestations ctdinduced pleuritis exhibits wide variety symptoms signs including exudative pleural effusions chest pain accurate estimation prevalence ctdrelated pleuritis challenging small effusions asymptomatic remain undetected rheumatoid arthritis systemic lupus erythematosus frequent ctds present pleural pathology approximately 520 1760 cases respectively contrast pleural involvement systemic sclerosis eosinophiliamyalgia syndrome mixed connective tissue disease ankylosing spondylitis polymyositis dermatomyositis syndrome rare clinical management depends severity symptoms however effusions resolve spontaneously review discuss pathophysiological mechanisms clinical considerations ctdinduced pleuritispmid33447289 pmcpmc7792825 doi101183 2073473502032020,0.0
hippocampal neurogenesis neural circuit formation cuprizoneinduced multiple sclerosis mouse model cognitive impairments key features multiple sclerosis ms progressive disorder characterized neuroinflammationinduced demyelination central nervous system understand neural substrates link demyelination cognitive deficits ms investigated hippocampal neurogenesis synaptic connectivity adultborn neurons play essential role cognitive function administration withdrawal combination cuprizone rapamycin cup rap c57bl 6j male mice efficiently demyelinated remyelinated hippocampus respectively demyelinated hippocampus neurogenesis nearly absent dentate gyrus due inhibited proliferation neural stem cells nscs specifically radial glialike type 1 nscs shifted proliferative state mitoticallyquiescent state demyelinated hippocampus addition dendritic spine densities adultborn neurons significantly decreased indicating reduction synaptic connections hippocampal newborn neurons excitatory input neurons concomitant hippocampal remyelination induced withdrawal cup rap proliferation type 1 nscs dendritic spine densities adultborn neurons reverted normal hippocampus study shows proliferation hippocampal nscs synaptic connectivity adultborn neurons inversely correlated level demyelination providing critical insight hippocampal neurogenesis potential therapeutic target treat cognitive deficits associated mssignificance statement identify neural substrates mediate cognitive dysfunctions associated majority ms patients investigated hippocampal neurogenesis structural development adultborn neurons using cup rap model recapitulates hippocampal demyelination occurs ms patients shift nscs proliferativelyactive state mitoticallyquiescent state dramatically decreased neurogenesis demyelinated hippocampus formation dendritic spines newborn neurons also impaired following demyelination interestingly altered neurogenesis synaptic connectivity newborn neurons reversed normal levels remyelination thus study revealed reversible genesis synaptic connectivity adultborn neurons demyelinated remyelinated hippocampus suggesting hippocampal neurogenesis potential target normalize cognitive impairments ms patients,1.0
attenuating neurogenic sympathetic hyperreflexia robustly improves antibacterial immunity chronic spinal cord injury spinal cord injury sci disrupts critical physiological systems including cardiovascular immune system plasticity spinal circuits injury results abnormal heightened sympathetic responses extreme sudden hypertension hallmarks lifethreatening autonomic dysreflexia moreover sympathetic hyperreflexia detrimentally impacts effector organs including spleen resulting spinal cord injuryinduced immunodeficiency consequently infection leading cause mortality sci unfortunately current treatments prophylactically limit sympathetic hyperreflexia prevent subsequent effector organ dysfunction cytokine soluble tumor necrosis factor stnf upregulated cns within minutes sci remains elevated report commencing intrathecal administration xpro1595 inhibitor stnf clinically feasible postinjury time point ie 3 d complete sci sufficiently diminishes maladaptive plasticity within spinal sympathetic reflex circuit results less severe autonomic dysreflexia realtime gauge sympathetic hyperreflexia months postinjury remarkably delayed delivery stnf inhibitor prevents sympathetic hyperreflexiaassociated splenic atrophy loss leukocytes dramatically improve endogenous ability chronic sci rats fight pneumonia common cause hospitalization injury improved immune function xpro1595 correlates less noradrenergic fiber sprouting normalized norepinephrine levels spleen indicating heightened central stnf signaling drives peripheral norepinephrinemediated organ dysfunction novel mechanism action thus preclinical study supports intrathecally targeting stnf viable strategy broadly attenuate sympathetic dysregulation thereby improving cardiovascular regulation immunity long scisignificance statement spinal cord injury sci significantly disrupts immunity thus increasing susceptibility infection leading cause morbidity living sci report commencing intrathecal administration inhibitor proinflammatory cytokine soluble tumor necrosis factor days injury sufficiently diminishes autonomic dysreflexia real time gauge sympathetic hyperreflexia prevent associated splenic atrophy dramatically improves endogenous ability chronically injured rats fight pneumonia common cause hospitalization preclinical study significant impact broadly improving quality life sci individuals,0.0
autophagy myelinating glia autophagy cellular process involved transportation degradation membrane proteins pathogens organelles fundamental cellular process vital development plasticity response disease injury compared neurons little information available autophagy glia paramount glia perform critical responses nervous system disease injury including active tissue remodeling phagocytosis myelinating glia autophagy expanded roles particularly phagocytosis mature myelin generating vast amounts membrane proteins lipids must transported form new myelin notably autophagy plays important roles removing excess cytoplasm promote myelin compaction development oligodendrocytes well remyelination schwann cells nerve trauma review summarizes cell biology autophagy detailing major pathways proteins involved well roles autophagy schwann cells oligodendrocytes development plasticity diseases myelin affected includes traumatic brain injury alexander9s disease alzheimer9s disease hypoxia multiple sclerosis hereditary spastic paraplegia others promising areas future research highlighted,1.0
aberrant er stress induced neuronalifn elicits white matter injury due microglial activation tcell infiltration tbi persistent endoplasmic reticulum er stress neurons associated activation inflammatory cells subsequent neuroinflammation following traumatic brain injury tbi however underlying mechanism remains elusive found induction neuronaler stress mostly characterized increase phosphorylation protein kinase rlike er kinase perk leads release excess interferon ifn due atypical activation neuronalsting signaling pathway ifn enforced activation polarization primary microglial cells inflammatory m1 phenotype secretion proinflammatory chemokine cxcl10 due activation stat1 signaling secreted cxcl10 turn stimulated tcell infiltration serving ligand chemoattractant cxcr3+ thelper 1 th1 cells activation microglial cells infiltration th1 cells resulted white matter injury characterized impaired myelin basic protein neurofilament nf200 reduced thickness corpus callosum external capsule decline mature oligodendrocytes oligodendrocyte precursor cells intranasal delivery cxcl10 sirna blocked th1 infiltration fully rescue microglial activation white matter injury tbi however impeding perkphosphorylation administration gsk2656157 abrogated neuronal induction ifn switched microglial polarization m2 phenotype prevented th1 infiltration increased th2 treg levels events ultimately attenuated white matter injury improved anxiety depressivelike behavior following tbisignificance statement recent clinical study showed human brain trauma patients enhanced expression type1 ifn suggests type1 ifn signaling may potentially influence clinical outcome tbi patients however understood tbi leads increase ifn whether induction ifn influence neuroinflammation primary reason morbidity mortality tbi study suggests induction perk phosphorylation characteristic feature er stress responsible increase neuronal ifn turn activates microglial cells subsequently manifests infiltration t cells induce neuroinflammation subsequently white matter injury blocking perk phosphorylation using gsk2656157 perk knockdown whole cascade neuroinflammation attenuated improved cognitive function tbi,1.0
lipid rafts neurodegeneration structural functional roles physiologic aging neurodegenerative diseases thematic review series biology lipid rafts j lipid res 2020 may 61 5 636654 doi 101194 jlrtr119000427 epub 2020 nov 7abstractlipid rafts small dynamic membrane areas characterized clustering selected membrane lipids result spontaneous separation glycolipids sphingolipids cholesterol liquidordered phase exact dynamics underlying phase separation membrane lipids complex biological membranes still fully understood nevertheless alterations membrane lipid composition affect lateral organization molecules belonging lipid rafts neural lipid rafts found brain cells including neurons astrocytes microglia characterized high enrichment specific lipids depending cell type lipid rafts seem organize determine function multiprotein complexes involved several aspects signal transduction thus regulating homeostasis brain progressive decline brain performance along physiological aging least part associated alterations composition structure neural lipid rafts addition neurodegenerative conditions lysosomal storage disorders multiple sclerosis parkinsons huntingtons alzheimers diseases frequently characterized dysregulated lipid metabolism turn affects structure lipid rafts several events underlying pathogenesis diseases appear depend altered composition lipid rafts thus structure function lipid rafts play central role pathogenesis many common neurodegenerative diseasespmid33715812 doi101194 jlrtr119000427,0.0
next 50 years neuroscience 50th anniversary society neuroscience reflect remarkable progress field made understanding nervous system look forward contributions next 50 years predict substantial acceleration understanding nervous system will drive development new therapeutic strategies treat diseases course next five decades also see neuroscience nexus many societal topics beyond medicine including education consumerism justice system combination advances made basic translational clinical neuroscience research next 50 years great potential lasting improvements human health economy society,0.0
oxidative stress vitamin d predictors multiple sclerosis curr health sci j 2020 octdec 46 4 371378 doi 1012865 chsj460407 epub 2020 dec 31abstractmultiple sclerosis ms multifactorial demyelinating diseases affect mostly young active people crucial identify new strategies order slow diseases progression maintain good functional outcome hypothesis interconnection antioxidant molecules antiinflammatory neuroprotective molecules can act predictors diseases progression study included 36 patients ms inclusion criteria following patients 18 years old divided three groups 16 relapsingremitting ms rrms group 10 secondary progressive ms spms group 10 healthy control group showed vitamin d sufficiency improve de edss score later stage diseases also showed early stage rrms vitamin d status can significantly improve edss iadl score may slow diseases progression started early stage diseases rrms found catalase activity enzyme act antioxidant significantly decreased compare healthy people can associated low level vitamin d concluded prooxidative antioxidative balance important player multifactorial mechanism ms diseases progression additional prospective studies needed determine optimal vitamin d levels lead clinical immunological benefits patients ms longterm followup studies using highdose vitamin d supplementation needed confirm preliminary results studiespmid33717511 pmcpmc7948027 doi1012865 chsj460407,1.0
protective effects nanoformulation curcumin cuprizoneinduced demyelination mouse corpus callosum iran j pharm res 2020 summer 19 3 310320 doi 1022037 ijpr202011295214033abstractmultiple sclerosis ms demyelinating disease central nervous system cns characterized neuroinflammation oligodendrocytes ols loss demyelination curcumin natural phenolic substance shown significant therapeutic properties various neurodegenerative diseases including ms laboratory loading curcumin dendrosome nanoparticles improved solubility bioavailability previous study showed antiinflammatory antioxidative effects dendrosomal nanocurcumin dnc experimental autoimmune encephalomyelitis eae model ms using toxic demyelination model induced cuprizone cpz investigated protective effect dnc oligodendroglial lineage cells ollc myelin preservation context acute demyelination cpz copper chelator thus intake reduces mitochondrial activity activates oxidative stress response leading specific ols death due highenergy consumption also evaluated dnc effect activation astrocytes microglia enriched ms cpz demyelinated lesions results demonstrated dnc treatment protected oligodendrocyte lineage cells ollcs cpz toxin besides dnc treatment suppressed accumulation astrocytes microglia cc cpzfed mice compared pbs treated onse moreover dnc treatment lead higher index luxol fast bluefast blue lfb myelinspecific proteins myelin basic protein mbp intensity corpus callosum cc indicators myelin content results suggest potent pleiotropic therapeutic efficiency dnc protection myelinating cells possibly via suppression astrocytes microgliapmid33680032 pmcpmc7758014 doi1022037 ijpr202011295214033,1.0
epsteinbarr virus infection development neurological disorders drug discov today dis models 2020 fall 32 pt 3552 doi 101016 jddmod202001001 epub 2020 feb 19abstractepsteinbarr virus ebv ubiquitous human herpesvirus contributes etiology diverse human cancers autoimmune diseases ebv establishes relatively benign longterm latent infection 90 percent adult population yet also increases risk certain cancers autoimmune disorders depending complex viral host environmental factors partly understood ebv latent infection found predominantly memory bcells natural infection cycle pathological aberrations enable ebv infect numerous cell types including oral nasopharyngeal gastric epithelia b t nklymphoid cells myocytes adipocytes astrocytes neurons ebv infected cells free virus gene products can also found cns addition direct effects ebv infected cells tissue effect chronic ebv infection immune system also thought contribute pathogenesis especially autoimmune disease review properties ebv infection may shed light potential pathogenic role neurological disorderspmid33897799 pmcpmc8059607 doi101016 jddmod202001001,0.0
cognitive performance relapsingremitting multiple sclerosis risk impaired dement geriatr cogn disord 2021 mar 1815 doi 101159 000514674 online ahead printabstractintroduction since cognitive impairment ci occurs average 45 multiple sclerosis ms patients early detection patients risk ci important order promptly apply preventive strategies aim present study investigate prevalence risk factors ci ms patients using brief international cognitive assessment multiple sclerosis bicams screening testmethods 1year period ci evaluated 82 consecutives mild relapsingremitting ms edss 35 patients patients 1 altered bicams test defined risk risk ci patients underwent extensive neuropsychological batteryresults found 23 ci ii 25 risk ci iii 76 risk patients already impaired np assessment particular symbol digit modalities test compromised 70 risk 79 ci patients patients ci frequently edss 25 p 005 lower education p 005 relapses last 12 months p 003 conclusions ci significant issue ms integration screening test sdmt routine clinical practice worth identify risk patients promote early therapeutic interventionpmid33735893 doi101159 000514674,0.0
delayed phases contrast mri can valuable multiple sclerosis active phase diagnosis caspian j intern med 2020 fall 11 4 432436 doi 1022088 cjim114432abstractbackground observing enhancing plaques magnetic resonance imaging mri one valuable diagnostic modalities confirming diagnosis multiple sclerosis ms recurrence better detection active disease since active lesions discovery can improve designating diffusion time diagnosis ms controlling disease activity definite time delay image acquisition therefore aim current study evaluate enhancement ms plaques different delayed phasesmethods interventional study receiving written consent 40 ms patients least one enhancing plaque previous mri evaluated babol ayatollah rouhani hospital gadolinium injected patients dose 01 mg kg mri taken 5 15 minutes results analyzed using spss 23 p005 considered significant levelresults mean plaque signal intensity 119020 134960 5 15 min respectively difference significant p0001 moreover mean plaque total size 516 cm 704 cm 5 15 min significant difference respectively p0001 mean plaque number 192 258 5 15 min respectively significantly different p0001 conclusion results indicated improvement detection ms plaques images taken delayed phase compared early phase plaque intensity size number significantly higher delayed phase 15 min early phase 5 min pmid33680386 pmcpmc7911766 doi1022088 cjim114432,0.0
healing influence melilotus officinalis herbal extract experimental autoimmune encephalomyelitis c57bl 6 mice iran j pharm res 2020 fall 19 4 321329 doi 1022037 ijpr202011380814505abstractthe present study designed primarily examine therapeutic potential herbal extract melilotus officinalis treatment multiple sclerosis experimental autoimmune encephalomyelitis eae model disease animal model induced c57bl 6 female mice herbal extract intraperitoneally administered total 21 days first day postimmunization phenotypic signs gene expression profile inflammatory cytokines antioxidant state pathological hallmarks disease corpus callosum evaluated prophylactic administration melilotus officinalis attenuates clinical signs disease significantly declined gene expression proinflammatory cytokines like il6 tnf ifn herbal extract also surged gene expression antiinflammatory cytokine gene expression glutathione peroxidase catalase antioxidant enzymes meaningfully higher treatment group pathological evaluation corpus callosum crosssections luxol fast blue staining revealed preserved myelin sheath treated group compared eae mice results assay confirmed immunomodulatory antioxidant features herbal extract melilotus officinalis ameliorated eae severity study finding disclosed therapeutic efficiency compound ms treatmentpmid33841545 pmcpmc8019886 doi1022037 ijpr202011380814505,1.0
effects 8week combined exercise training inflammatory markers women multiple sclerosis neurodegener dis 2021 jul 20 doi 101159 000518580 online ahead printno abstractpmid34348347 doi101159 000518580,0.0
potential role trace elements al cu zn se multiple sclerosis physiopathology neuroimmunomodulation 2021 mar 10115 doi 101159 000511308 online ahead printabstractmultiple sclerosis ms unpredictable disease central nervous system cause ms known completely pathology specified involved demyelinated areas white gray matter brain spinal cord inflammation peripheral tolerance breakdown due treg cell defects effector cell resistance present stages disease several invading peripheral immune cells included process disease macrophages cd8+ t cells cd4+ t cells b cells plasma cells trace elements known elements found soil plants living organisms small quantities eg al cu zn mn se essential bodys functions like catalysts enzyme systems energy metabolism etc al toxicity cu zn se toxicity deficiency can affect immune system following neuron inflammation degeneration processes may result ms pathology course factors lifestyle environment industrialization can affect levels trace elements human bodypmid33691322 doi101159 000511308,1.0
sphingosine kinase 2 potentiates amyloid deposition protects hippocampal volume loss demyelination mouse model alzheimer#39 s disease sphingosine 1phosphate s1p potent vasculoprotective neuroprotective signaling lipid synthesized primarily sphingosine kinase 2 sk2 brain reported pronounced loss s1p sk2 activity early alzheimer9s disease ad pathogenesis inverse correlation hippocampal s1p levels age females leading us speculate loss s1p sensitizing influence ad paradoxically sk2 reported mediate amyloid formation amyloid precursor protein app vitro determine whether loss s1p sensitizes amediated neurodegeneration investigated whether sk2 deficiency worsens pathology memory male j20 pdgfbappswind mice sk2 deficiency greatly reduced content j20 mice associated significant improvements epileptiform activity crossfrequency coupling measured hippocampal electroencephalography however several key measures appswinddependent neurodegeneration enhanced sk2null background despite reduced burden included hippocampal volume loss oligodendrocyte attrition myelin loss impaired performance ymaze social novelty memory tests inhibition endosomal cholesterol exporter npc1 greatly reduced sphingosine phosphorylation glial cells linking loss sk2 activity s1p ad perturbed endosomal lipid metabolism findings establish sk2 important endogenous regulator app processing oligodendrocyte survival vivo results urge greater consideration roles played oligodendrocyte dysfunction altered membrane lipid metabolic flux drivers neurodegeneration adsignificance statement genetic neuropathological functional studies implicate altered lipid metabolism signaling key pathogenic drivers alzheimer9s disease study first demonstrate enzyme sk2 generates signaling lipid s1p required formation app vivo second establish new role sk2 protection oligodendrocytes myelin loss sk2 sensitizes amediated neurodegeneration attenuating oligodendrocyte survival promoting hippocampal atrophy despite reduced burden findings support model aindependent sensitizing influences loss neuroprotective s1p important drivers neurodegeneration gross concentration plaque density,1.0
p75ntr dr6 regulate distinct phases axon degeneration demarcated spheroid rupture regressive events associated trophic deprivation critical sculpting functional nervous system nerve growth factor withdrawal sympathetic axons derived male female neonatal mice maintain structural integrity 18 h latent phase followed rapid near unison disassembly axons next 3 h catastrophic phase examine molecular basis axons transition latent catastrophic phases degeneration following trophic withdrawal catastrophic degeneration observed increase intraaxonal calcium calcium flux accompanied p75 neurotrophic factor receptorrhoactindependent expansion calciumrich axonal spheroids eventually rupture releasing contents extracellular space conditioned media derived degenerating axons capable hastening transition catastrophic phase degeneration also found death receptor 6 p75 neurotrophic factor receptor required transition catastrophic phase response conditioned media intraaxonal calcium flux spheroid formation rupture occur toward end latency results support existence interaxonal degenerative signal promotes catastrophic degeneration among trophically deprived axonssignificance statement developmental pruning shares several morphological similarities disease injuryinduced degeneration including spheroid formation function underlying mechanisms governing axonal spheroid formation however remain unclear study report axons coordinate other9s degeneration development via axonal spheroid rupture irreversible breakdown axon response trophic withdrawal p75 neurotrophic factor receptorrhoa signaling governs formation growth spheroids spheroids rupture allowing exchange contents 10 kda intracellular extracellular space drive death receptor 6 calpaindependent catastrophic degeneration finding informs understanding regressive events development may also provide rationale designing new treatments toward myriad neurodegenerative disorders,0.0
dorsal hippocampal actin polymerization necessary activation gproteincoupled estrogen receptor gper increase ca1 dendritic spine density enhance memory consolidation activation membrane estrogen receptor gproteincoupled estrogen receptor gper ovariectomized mice via gper agonist g1 mimics beneficial effects 17estradiol e2 hippocampal ca1 spine density memory consolidation yet cellsignaling mechanisms mediating effects remain unclear present study examined role actin polymerization cjun nterminal kinase jnk phosphorylation mediating effects dorsal hippocampally infused g1 ca1 dendritic spine density consolidation object recognition spatial memories ovariectomized mice first showed object learning increased apical ca1 spine density dorsal hippocampus dh within 40 min found dh infusion g1 increased ca1 spine density phosphorylation actin polymerization regulator cofilin suggesting activation gper may increase spine morphogenesis actin polymerization memory consolidation previous work kim et al 2016 effects g1 ca1 spine density cofilin phosphorylation depended jnk phosphorylation dh also consistent previous findings e2induced cofilin phosphorylation dependent gper activation finally found infusion actin polymerization inhibitor latrunculin dh prevented g1 increasing apical ca1 spine density enhancing object recognition spatial memory consolidation collectively data demonstrate gpermediated hippocampal spinogenesis memory consolidation depend jnk cofilin signaling supporting critical role actin polymerization gperinduced regulation hippocampal function female micesignificance statement emerging evidence suggests gproteincoupled estrogen receptor gper activation mimics effects 17estradiol hippocampal memory consolidation unlike canonical estrogen receptors gper activation associated reduced cancer cell proliferation thus understanding molecular mechanisms gper regulates hippocampal function may provide new avenues development drugs provide cognitive benefits estrogens without harmful side effects demonstrate gper increases ca1 dendritic spine density hippocampal memory consolidation manner dependent actin polymerization cjun nterminal kinase phosphorylation findings provide novel insights role gper mediating hippocampal morphology memory consolidation may suggest first steps toward new therapeutics safely effectively reduce memory decline menopausal women,0.0
neuroevs characterizing extracellular vesicles generated neural domain intercellular communication recently shown occur via transfer cargo loaded within extracellular vesicles evs present within biofluids body evs can contain various signaling factors including coding noncoding rnas eg mrna mirna lncrna snrna trna yrna dna proteins enzymes multiple types cells appear capable releasing evs including cancer stem epithelial immune glial neuronal cells however functional impact circulating signals among neural networks within brain difficult establish given complexity cellular populations involved release uptake well inherent limitations examining biofluid brief commentary provide analysis conceptual technical considerations limit current understanding signaling mediated circulating evs relative impact neural functiondual perspectives companion paperextracellular vesicles neurodegenerative diseases andrew f hill,0.0
white matter stroke induces unique oligoastrocyte niche inhibits recovery subcortical white matter stroke common stroke subtype white matter stroke stimulates adjacent oligodendrocyte progenitor cells opcs divide migrate lesion stroke opcs limited differentiation mature oligodendrocytes understand molecular systems active opc responses white matter stroke opcs virally labeled lasercaptured region partial damage adjacent infarct male mice rnaseq indicates two distinct opc transcriptomes associated proliferative limitedregeneration phases opcs stroke molecular pathways related nuclear receptor activation ecm turnover lipid biosynthesis activated proliferative opc phases stroke inflammatory growth factor signaling activated later stage limited opc differentiation within ecm proteins matrilin2 induced early stroke rapidly downregulated prediction upstream regulators opc stroke transcriptome identifies several candidate molecules including inhibin aa negative regulator matrilin2 inhibin induced reactive astrocytes stroke including humans functional assays matrilin2 induces opc differentiation inhibin inhibits opc matrilin2 expression inhibits opc differentiation vivo matrilin2 promotes motor recovery white matter stroke promotes opc differentiation ultrastructural evidence remyelination studies show white matter stroke induces initial proliferative reparative response opcs blocked local cellular niche reactive astrocytes secrete inhibin downregulating matrilin2 blocking myelin repair recoverysignificance statement stroke cerebral white matter brain common biology damage recovery stroke subtype well defined studies use cellspecific rna sequencing gainoffunction studies show white matter stroke induces glial signaling niche present humans mice reactive astrocytes oligodendrocyte progenitor cells astrocyte secretion inhibin downregulation oligodendrocyte precursor production matrilin2 limit opc differentiation tissue repair recovery disease,1.0
multiple sclerosis adults management nice cg186 guideline covers diagnosing managing multiple sclerosis people aged 18 aims improve quality life adults multiple sclerosis,0.0
growing interest medical marijuana relaxed state laws wider availability use cannabis cannabinoids increasing throughout united states pts ptas need know patients can affected positive negative ways,0.0